Alpha-fetoprotein associated with islet cell tumors.
Elevated serum levels of alpha-fetoprotein (AFP) (100-1,000 ng/ml) were found in three patients with islet cell tumors. Serial levels correlated with progression of disease, suggesting that AFP could be a useful tumor marker substance for islet cell tumors. Survey sera from an expanded pool of 23 patients with islet cell tumors and nine with carcinoid tumors did not identify additional cases, however, suggesting that elevated AFP levels in these classes of Apudomas are uncommon. Nonetheless, the distinction from other AFP-producing tumors such as hepatocellular carcinoma is clinically important and warrants an awareness of the rare association of AFP with these tumors.


Estrogens and androgens inhibit association of RANKL with the pre-osteoblast membrane through post-translational mechanisms.
We have recently demonstrated that RUNX2 promoted, and 17β-Estradiol (E2) diminished, association of RANKL with the cell membrane in pre-osteoblast cultures. Here we show that, similar to E2, dihydrotestosterone (DHT) diminishes association of RANKL, and transiently transfected GFP-RANKL with the pre-osteoblast membrane without decreasing total RANKL mRNA or protein levels. Diminution of membrane-associated RANKL was accompanied with marked suppression of osteoclast differentiation from co-cultured pre-osteoclasts, even though DHT increased, not decreased, RANKL concentrations in pre-osteoblast conditioned media. A marked decrease in membrane-associated RANKL was observed after 30 min of either E2 or DHT treatment, and near-complete inhibition was observed by 1 hr, suggesting that the diminution of RANKL membrane association was mediated through non-genomic mechanisms. Further indicating dispensability of nuclear action of estrogen receptor, E2-mediated inhibition of RANKL membrane association was mimicked by an estrogen dendrimer conjugate (EDC) that cannot enter the cell nucleus. Finally, the inhibitory effect of E2 and DHT on RANKL membrane association was counteracted by the MMP inhibitor NNGH, and the effect of E2 (and not DHT) was antagonized by the Src inhibitor SU6656. Taken together, these results suggest that estrogens and androgens inhibit osteoblast-driven osteoclastogenesis through non-genomic mechanism(s) that entail, MMP-mediated RANKL dissociation from the cell membrane.


[The spectrum of analgesic activity of baclofen and tolibut].
Spectrum of the analgetic activity of GABA derivatives baclofen (2.5-10.0 mg/kg) and tolibut (12.5-100.0 mg/kg) was studied in experiments on albino mice and rats. Baclofen and especially tolibut showed a dose-dependent inhibition of perceptive, emotional and autonomic manifestations of nociceptive reactions at the tail's thermal and electrical stimulation and enhancement of the analgetic effect of promedol. The regressive analysis made it possible to show dependence of the analgetic effect on the level of pain sensitivity and emotional reactivity of the animals. Tolibut deepens and prolongs sombrevin anesthesia, baclofen fails to alter it.


Endocrine-Disrupting Chemicals and Disorders of Penile Development in Humans.
This paper reviews the current knowledge on the environmental effects on penile development in humans. The specific focus is on endocrine-disrupting chemicals (EDCs), a heterogeneous group of natural or manmade substances that interfere with endocrine function, and whether they can induce hypospadias and micropenis in male neonates. Epidemiological data and animal observations first raised suspicions about environmental effects, leading to the testis dysgenesis syndrome (TDS) hypothesis. More recent research has provided stronger indications that TDS may indeed be the result of the direct or indirect effects of EDCs. Drawing on epidemiological and toxicological studies, we also report on the effects of maternal diet and substances like pesticides, phthalates, bisphenol A, and polychlorinated biphenyls. Proximity to contamination hazards and occupational exposure are also suspected to contribute to the occurrence of hypospadias and micropenis. Lastly, the cumulative effects of EDCs and the possibility of transgenerational effects, with the penile development of subsequent generations being affected, raise concerns for long-term public health.


The Reproductive Injustices of Abortion Bans for Disability.
This article argues that state laws banning abortions for disability violate reproductive justice for parents with disabilities. These bans deprive people with disabilities of choices that may be important to their possibilities of becoming parents, including possibilities for abortion of pregnancies that have become risky to continue. Far from protecting disability civil rights, these state law bans restrict the abilities of people with disabilities to choose to have children and to parent.


Response of extensive breast cancer skin metastases to rechallenge with trastuzumab together with low-dose chemotherapy and insulin.
Cutaneous metastasis occurs in about 29% of breast cancer patients and has a deep impact on patient quality of life. A 60-year-old woman with cutaneous metastases from heavily pretreated HER2-positive breast cancer received CMFVP (oral cyclophosphamide 100 mg daily; oral prednisone 12.5 mg daily for 2 weeks, then 7.5 mg daily; intravenous weekly methotrexate 25 mg/m2, 5-5-fluorouracil 400 mg/m2 and vincristine 0.5 mg) with weekly trastuzumab and subcutaneous insulin until disease progression. From March 2009 to November 2009 the patient was treated with the described regimen. At the best response, we observed the disappearance of some lesions and cessation of bleeding and thoracic pain. Time to progression was 8 months. Our patient had clinical benefit from reintroduction of trastuzumab, low-dose chemotherapy and insulin. The explanation of this prolonged response is only speculative and requires further clinical confirmation in the treatment strategy of HER2-positive breast cancer.


Large animal ventilator-integrated volumetric capnography generates clinically acceptable values of physiologic dead space in anesthetized healthy adult horses.
To evaluate the agreement between the Tafonius large animal ventilator-integrated volumetric capnography (vCap) software and the Respironics NICO noninvasive cardiac output monitor reference system. Data were collected from 56 healthy adult horses undergoing general anesthesia. Animals were placed under general anesthesia and connected to the Tafonius large animal ventilator circle system. A flow partitioning device with CO2 and flow sensors was utilized to couple the endotracheal tube to the NICO monitor. Tafonius CO2 and flow sensors are incorporated into the Y-piece of the breathing circuit. Arterial blood samples were collected to determine the partial pressure of arterial carbon dioxide (PaCO2) immediately before data collection. The PaCO2 was input into the Tafonius and NICO monitor, and dead space ventilation (%Vd), end-tidal CO2 partial pressure (ETco2), mixed-expired CO2 partial pressure (Peco2), and expired tidal volume (Vt) were calculated over a single breath. Multiple measurements were completed for each patient, with a total of 200 paired data points collected for analysis. Data were assessed for normality, and Bland-Altman analysis was performed. Bias and 95% limits of agreement were calculated. The limits of agreement for %Vd of the ventilator-derived measurements fell within ± 10% of the NICO monitor reference method. Our results indicate that, when compared to the NICO monitor method, the Tafonius-integrated vCap software provides clinically acceptable values of Peco2, Vt, and %Vd in healthy adult horses.


Bacteria and pH-sensitive polysaccharide-polymer films for colon targeted delivery.
The colon provides drug delivery opportunities for colon-specific and systemic delivery of various therapeutic agents. Different strategies have been utilized in targeting drugs to the colon. Recently, integrated systems which incorporate dual mechanisms in colon targeted delivery have received a lot of attention. Of particular interest is bacteria-aided biomaterials and pH-sensitive polymeric film (BPSF) coating for colon targeted drug delivery. The major constituents of these films are polysaccharides and pH-sensitive polymers. The pH-sensitive polymer retards drug release in the stomach and small intestine, while the polysaccharide is digested by colonic enzymes. Digestion of the polysaccharides by bacterial glycosidic enzymes increases the pore density in the film to facilitate drug release. Generally, bacteria-aided biomaterials and pH-sensitive films can be applied to the delivery of most small organic molecules to the colon. The review encompasses the pharmaceutical design parameters such as film digestibility, swelling index and dry mass loss (that provide molecular mechanistic analysis of film permeability) as well as tensile strength, elastic modulus, and elongation at break (that describe the desirable mechanical properties of the films). A critical analysis of formulation, techniques for characterization of film properties and drug-release kinetics from these systems are emphasized.


Diffusional transport to and through thin-layer nanoparticle film modified electrodes: capped CdSe nanoparticle modified electrodes.
We present a simple and general theoretical model which accounts fully for the influence of an electrode modifying non-electroactive layer on the voltammetric response of a diffusional redox probe. The layer is solely considered to alter the solubilities and diffusion coefficients of the electroactive species within the thin layer on the electrode surface. On this basis it is demonstrated how, first, the apparent electrochemical rate constant can deviate significantly from that measured at an unmodified electrode. Second, depending on the conditions within the layer the modification of the electrode may lead to either apparent 'negative' or 'positive' electrocatalytic effects without the true standard electrochemical rate constant for the electron transfer at the electrode surface being altered. Having presented the theoretical model three experimental cases are investigated, specifically, the reductions of ruthenium(III) hexaamine, oxygen and boric acid on a gold macro electrode with and without a multi-layer organic capped nanoparticle film. In the latter case of the reduction of boric acid the voltammetric reduction is found to be enhanced by the presence of the organic layer. This result is interpreted as being due to an increase in the solubility of the analyte within the non-electroactive layer and not due to an alteration of the standard electrochemical rate constant.


[Public health research: are there differences among northern, southern and eastern European countries? A perspective from national associations of public health].
Research provides the important evidence base for public health practice. We sought to compare the current support for public health research within European countries. Within a collaborative study SPHERE (Strengthening Public Health Research in Europe), we developed an e-mail questionnaire and sent it to 93 representatives of national member associations of the European Public Health Association. We compared the answers with reference to tree macro-areas: Northern, Southern and Eastern Europe. We gained responses for 22 of 39 European countries (56% country response rate). Current priorities at national level were: health service and patient safety for Northern Europe; infectious disease, health service and cardiovascular disease for Southern Europe; and food safety and nutrition, environmental and occupational health for Eastern Europe. Respondents gave fewer priorities for international research. In the North Europe the priorities empathized were health promotion, prevention and education (26.3%) together the injuries and alcohol habits (26.3%). Support for public-health research differs across Europe, and barriers to undertaking better research include structures and sufficient personnel. National public health associations and public authorities should cooperate in order to find effective answers to common problems.


Implementation of regional Acute Stroke Care Map increases thrombolysis rates for acute ischaemic stroke in Chinese urban area in only 3 months.
The rate of intravenous thrombolysis for acute ischaemic stroke remains low in China. We investigated whether the implementation of a citywide Acute Stroke Care Map (ASCaM) is associated with an improvement of acute stroke care quality in a Chinese urban area. The ASCaM comprises 10 improvement strategies and has been implemented through a network consisting of 20 tertiary hospitals. We identified 7827 patients with ischaemic stroke admitted from April to October 2017, and 506 patients underwent thrombolysis were finally included for analysis. Compared with 'pre-ASCaM period', we observed an increased rate of administration of tissue plasminogen activator within 4.5 hours (65.4% vs 54.5%; adjusted OR, 1.724; 95% CI 1.21 to 2.45; p=0.003) during 'ASCaM period'. In multivariate analysis models, 'ASCaM period' was associated with a significant reduction in onset-to-door time (114.1±55.7 vs 135.7±58.4 min, p=0.0002) and onset-to-needle time (ONT) (169.2±58.1 vs 195.6±59.3 min, p<0.0001). Yet no change was found in door-to-needle time. Clinical outcomes such as symptomatic intracranial haemorrhage, favourable functional outcome (modified Rankin Scale ≤2) and in-hospital mortality remained unchanged. The implementation of ASCaM was significantly associated with increased rates of intravenous thrombolysis and shorter ONT. The ASCaM may, in proof-of-principle, serve as a model to reduce treatment delay and increase thrombolysis rates in Chinese urban areas and possibly other highly populated Asian regions.


Infliximab dose reduction sustains the clinical treatment effect in active HLAB27 positive ankylosing spondylitis: a two-year pilot study.
The rationale of the study was to evaluate the efficacy of infliximab (IFX) treatment in patients with ankylosing spondylitis (AS) and to determine whether IFX dose reduction and interval extension sustains the treatment effect. Nineteen patients were included and treated with IFX 5 mg/kg every 6 weeks for 56 weeks. All patients concomitantly received MTX with median dose 7.5 mg/weekly. During the second year, the IFX dose was reduced to 3 mg/kg every 8 weeks. Eighteen patients completed the 1-year and 15 patients the 2-year trial. The ≥50% improvement at week 16 from baseline of BASDAI was achieved in 16/19 (84%) patients. Significant reductions in BASDAI, BASFI, and BASMI scores, decrease in ESR and CRP, and improvement in SF-36 were observed at weeks 16 and 56. The MRI-defined inflammatory changes in the sacroiliac joints disappeared in 10/15 patients (67%) already at 16 weeks. IFX treatment effect was sustained throughout the second year after IFX dose reduction and interval extension. We conclude that IFX treatment is effective in well-established active AS and a dose reduction sustains the treatment effect. These observations are of clinical importance and open the opportunity to reduce the drug costs.


Prophylactic epicardial pacemaker implantation in tricuspid valve replacement.
Patients undergoing surgical tricuspid valve replacement (TVR) are at high risk of atrioventricular conduction disorders. Because implanting a lead through the tricuspid bioprosthesis is discouraged, the patients who undergo TVR in our centre are usually given a prophylactic epicardial pacemaker. Our aim was to assess the benefits and risks of this strategy. Among the patients who underwent TVR with prophylactic epicardial pacemaker implantation, clinical evaluations and pacemaker reports were analysed retrospectively after surgery. The need for cardiac pacing were assessed by characterising the atrioventricular conduction, while the risks were evaluated by listing and adjudicating post-operative events. 80 patients were analysed (mean age was 57 ± 16 years old, 30% males). TVR was isolated in 28 (35%) patients, but most often associated with another valve surgery. In the postoperative period, heart rhythm was analysed in 59/80 patients during a median follow-up of 35 months. Cardiac pacing was needed in 46% patients: 14% had complete pacing dependency, 17% had high degree AV block, while 15% had a high ventricular pacing rate (>80%). No pre- or per-operative variables could predict cardiac pacing requirement. Post-operatively, a spontaneous heart rate >70bpm (P = 0.02) and the presence of narrow QRS (P = 0.03) were significantly associated with a lower risk of cardiac pacing requirement. Complications related to epicardial pacemaker were documented in 2 (2.5%) patients. After TVR, cardiac pacing was needed in 46% of patients for post-operative atrioventricular conduction disorders. This high incidence associated with an acceptable safety profile supports a prophylactic epicardial pacing strategy for the patients undergoing TVR.


Discrete Choice Models for Nonmonotone Nonignorable Missing Data: Identification and Inference.
Nonmonotone missing data arise routinely in empirical studies of social and health sciences, and when ignored, can induce selection bias and loss of efficiency. In practice, it is common to account for nonresponse under a missing-at-random assumption which although convenient, is rarely appropriate when nonresponse is nonmonotone. Likelihood and Bayesian missing data methodologies often require specification of a parametric model for the full data law, thus a priori ruling out any prospect for semiparametric inference. In this paper, we propose an all-purpose approach which delivers semiparametric inferences when missing data are nonmonotone and not at random. The approach is based on a discrete choice model (DCM) as a means to generate a large class of nonmonotone nonresponse mechanisms that are nonignorable. Sufficient conditions for nonparametric identification are given, and a general framework for fully parametric and semiparametric inference under an arbitrary DCM is proposed. Special consideration is given to the case of logit discrete choice nonresponse model (LDCM) for which we describe generalizations of inverse-probability weighting, pattern-mixture estimation, doubly robust estimation and multiply robust estimation.


Continuous Reproductive Surveillance.
The Dobbs opinion emphasizes that the state's interest in the fetus extends to "all stages of development." This essay briefly explores whether state legislators, agencies, and courts could use the "all stages of development" language to expand reproductive surveillance by using novel developments in consumer health technologies to augment those efforts.


Individually tailored treatment targeting activity, motor behavior, and cognition reduces pain-related disability: a randomized controlled trial in patients with musculoskeletal pain.
This study compares the outcomes of an individually tailored behavioral medicine intervention (experimental) with physical exercise therapy (control). The experimental intervention was systematically individualized according to each participant's behavioral treatment goals and functional behavioral analyses. One hundred twenty-two patients seeking care at 3 primary health care clinics because of musculoskeletal pain were randomized. Ninety-seven completed the trial. Data were collected at baseline, immediately after treatment, and at a 3-month follow-up. Analyses of data from completers, as well as intention-to-treat analyses, showed that the experimental group experienced lower levels of disability (P = .01), lower maximum pain intensity (P = .02), higher levels of pain control (P = .001), and lower fear of movement (P = .022) as a result of treatment condition. Self-efficacy (P = .0001) and physical performance (P = .0001) increased over time for both groups. Participants in the experimental group generally reported more positive effects after treatment. Treatment fidelity was maintained during the course of the study. Activity can be resumed and pain might be managed by the patients themselves if treatment incorporates the biopsychosocial explanatory model of pain and strategies are tailored according to individual's priorities of everyday life activities and empirically derived determinants of pain-related disability. This study shows that the biomedical and the psychosocial perspectives of the experiences and consequences of pain complement rather than contradict each other. Primary health care patients with persistent musculoskeletal pain benefit more from a systematic tailoring of treatments according to biopsychosocial factors than from a physically based exercise intervention.


Castor cake as organic fertilizer to control gastrointestinal nematodes in pasture-raised sheep.
Gastrointestinal parasitism is one of the factors that discourages farmers from raising small ruminants in cultivated pastures. To validate a soil treatment strategy to control the free-living stages of gastrointestinal nematodes (GIN), castor cake (CC) was used as a fertilizer on a pasture where sheep grazed on guinea grass under continuous stocking. On day zero, the pasture was divided into three paddocks, contaminated by GIN and treated, respectively, with CC divided into two applications (2CC1/2), CC in a single application (CC1) and organic compost in a single application (control). On day 21, eight GIN-free sheep were placed in each paddock. On day 58, significant differences (P<0.05) were observed: reduction of up to 66.10% in larvae.g-1 of dry mass in pastures fertilized with CC, decrease of up to 60.72% in infection rates among the animals in the groups treated with CC, higher average daily weight gain (over 185 g.day-1) and packed cell volume (over 26%) in the groups treated with CC, when compared to the control (128 g.day-1; 20.9%). In view of the results, the use of CC, mainly CC1, as a fertilizer for guinea grass pastures, under continuous stocking, proved to be promising, with 63.41% effectiveness in controlling worm infestations.


The value of beta-lipotrophin measurement during the short metyrapone test in patients with pituitary diseases and in Cushing's syndrome.
Serum 11-deoxycortisol (S) determination has been used to evaluate the pituitary adrenal response to the short metyrapone (MTP) test. The validity of this indirect evaluation of corticotrophin ACTH reserve has been questioned since the MTP-induced S elevation may reflect a passive accumulation rather than an ACTH activated adrenal response. The purpose of this study was to evaluate the usefulness of serum beta-lipotrophin (beta-LPH) measurement during the short midnight MTP test (30 mg/kg body weight) in patients with pituitary diseases (n = 36) and in patients with Cushing's syndrome (n = 8). In 28/36 patients with pituitary diseases both S and beta-LPH concentrations were increased normally by MTP. In 8/36 patients the beta-LPH response was lacking, while their serum S concentrations increased significantly. The absence of beta-LPH response to MTP in these 8 patients was in good agreement with the diagnosis of ACTH insufficiency because in 7 of them the cortisol response to insulin induced hypoglycaemia was also insufficient. In the 8 patients with Cushing's syndrome serum S concentration increased following MTP administration in all the cases. In 2 with adrenal adenoma the increase of S level was an ACTH-independent phenomenon, since beta-LPH level was undetectable both before and after MTP administration. In 2 patients with ectopic ACTH secretion, the basal beta-LPH concentrations were high and remained unmodified by MTP administration. In the 4 patients with Cushing's disease, MTP administration resulted in a dramatic increase of beta-LPH concentration. We conclude that beta-LPH measurement improves the utility of the short MTP test for investigation of pituitary adrenal function.


An analysis of 100 primary cadaver kidney transplants.
A multifactorial analysis of 100 consecutive first cadaver kidney transplants was done to document the current status of this treatment for end stage renal disease and to determine the influence of the following variables on kidney losses owing to rejection: splenectomy, pre-transplant transfusions, transfusion at the transplantation, recipient sex, pre-transplant nephrectomy, donor and recipient A, B or O blood group, human leukocyte A and B antigen mismatches, kidney preservation method, donor treatment with methylprednisolone and cyclophosphamide, recipient treatment with antilymphocyte serum or antilymphoblast globulin and a low dose of steroid treatment for rejection. Pre-transplant splenectomy for leukopenia, 5 or more pre-transplant blood transfusions and pre-transplant transfusions without development of circulating cytotoxic antibodies significantly reduced kidney losses owing to rejection (p less than 0.05)., A low dose of steroid treatment for rejection resulted in a trend towards improved patient survival without sacrificing kidney graft survival. Clinical studies demonstrating decreases in kidney graft rejection should be controlled for pre-transplant blood transfusions and, possibly, for pre-transplant splenectomy for hypersplenism.


Intrapopulation genome size variation in D. melanogaster reflects life history variation and plasticity.
We determined female genome sizes using flow cytometry for 211 Drosophila melanogaster sequenced inbred strains from the Drosophila Genetic Reference Panel, and found significant conspecific and intrapopulation variation in genome size. We also compared several life history traits for 25 lines with large and 25 lines with small genomes in three thermal environments, and found that genome size as well as genome size by temperature interactions significantly correlated with survival to pupation and adulthood, time to pupation, female pupal mass, and female eclosion rates. Genome size accounted for up to 23% of the variation in developmental phenotypes, but the contribution of genome size to variation in life history traits was plastic and varied according to the thermal environment. Expression data implicate differences in metabolism that correspond to genome size variation. These results indicate that significant genome size variation exists within D. melanogaster and this variation may impact the evolutionary ecology of the species. Genome size variation accounts for a significant portion of life history variation in an environmentally dependent manner, suggesting that potential fitness effects associated with genome size variation also depend on environmental conditions.


Getting out of the bay faster: assessing trauma team performance using trauma video review.
Minutes matter for trauma patients in hemorrhagic shock. How trauma team function impacts time to the next phase of care has not been rigorously evaluated. We hypothesized better team performance scores to be associated with decreased time to the next phase of trauma care. This retrospective secondary analysis of a prospective multicenter observational study included hypotensive trauma patients at 19 centers. Using Trauma Video Review, we analyzed team performance with the validated T-NOTECHS scale (non-technical skills scale for trauma): leadership, cooperation and resource management, communication, assessment/decision making, and situational awareness. The primary outcome was minutes from patient arrival to next phase of care; deaths in the bay were excluded. Secondary outcomes included time to initiation and completion of first unit of blood and inpatient mortality. Associations between team dynamics and outcomes were assessed with a linear mixed effects model adjusting for injury severity score (ISS), mechanism, initial blood pressure and heart rate, number of team members, and trauma team lead training level and gender. 441 patients were included. The median ISS was 22 [IQR:10-34] and most (61%) sustained blunt trauma. Median time to next phase of care was 23.5 [17-35] minutes. Better leadership, communication, assessment/decision making, and situational awareness scores were associated with faster times to next phase of care (all p < 0.05). Each 1-point worsening in the T-NOTECHS score (scale:5-15) was associated with 1.6 minutes more in the bay. The median resuscitation team size was 12 [10-15], and larger teams were slower (p < 0.05). Better situational awareness was associated with faster completion of first unit of blood by 4-5 minutes (p < 0.05). Better team performance is associated with faster transitions to next phase of care in hypotensive trauma patients, and larger teams are slower. Trauma team training should focus on optimizing team performance to facilitate faster hemorrhage control. Level III.


[Effects of pyrrolidine dithiocarbamate on expressions of α-smooth muscle actin, integrin α5 and fibronectin in acute paraquat poisoned rats].
To observe the expressions of α-SMA, integrin α5 and fibronectin (Fn) in acute paraquat poisoned rats and the effect of PDTC. To investigate the mechanism of paraquat-induced pulmonary fibrosis. Sprague-Dawley rats were randomly divided into three experimental groups: Control group (6 rats), PQ group (36 rats) and PQ+PDTC group (36 rats). On the 1st, 3rd, the 7th, the 14th, the 28th and the 56th day after exposure, the protein expression of α smooth muscle actin (α-SMA) was evaluated by western blot. The mRNA levels of integrin α5 and fibronectin (Fn) were analyzed with real-time quantitative PCR (RT-PCR). Meanwhile, the lung pathological changes were observed and semi-quantified. T With the time passing, the expression of α-SMA in PQ group increased gradually compared with control group (P < 0.05 or P < 0.01). The increasing extent was gently on the 3 rd, the 7 th day. While increasing extent was rapidly from the 28 th to the 56 th day. RT-PCR showed PQ significantly increased Fn mRNA level on all time points and increased integrin α5 mRNA level from the 7 rd to 56 th day compared with control group (P < 0.05 or P < 0.01). PDTC treatment significantly deceased α-SMA, Fn, and integrin α5 levels compared with PQ group in corresponding time points (P < 0.05 or P < 0.01) Noteworthy, in PQ+PDTC group, the occurrence of pathological changes were drastically attenuated and pathologic score significantly decreased (P < 0.05 or P < 0.01). α-SMA, integrin α5 and fibronectin could play an important role in the development of pulmonary fibrosis caused by paraquat poisoning. PDTC, asa strong NF-κB inhibitor, may inhibit NF-κB activity and further significantly decreased expressions of α-SMA, integrin α5 and fibronectin which were important part of ECM, leading to drastically attenuated pulmonary fibrosis. However, the mechanisms of PDTC intervention still remains to be explored.


The meaning and relevance of B-cell receptor structure and function in chronic lymphocytic leukemia.
The B-cell receptor (BCR) is of critical importance for normal B cells and for the majority of B-cell malignancies, especially chronic lymphocytic leukemia (CLL). The two major subsets of CLL are biologically distinct, being derived from B cells at different stages of differentiation and carrying unmutated (U-CLL) or mutated (M-CLL) IGHV genes. U-CLL, which has a poorer prognosis, often has relatively conserved (stereotypic) IGHV-HD-HJ sequences, indicative of interaction with large (super)antigens and similar to those in normal naive innate B cells. Conserved sequences are less evident in M-CLL, in keeping with its postfollicular origin. However, both subsets exhibit features of chronic antigen exposure in tissue sites, with local proliferative events, but also downregulation of surface immunoglobulin M but not surface immunoglobulin D, a characteristic of normal anergic B cells. BCR-mediated anergy can spread to other receptors such as CXCR4. Circulating CLL cells retain a shadow of tissue-based events that can reverse over time, but the overall extent of anergy is greater in M-CLL. Despite this stereotypic variety and more genomic complexity, BCR-mediated responses in vitro appear relatively homogeneous in U-CLL, but M-CLL is more heterogeneous. The differential balance between antigen-induced proliferation or anergy is the likely determinant of clinical behavior and possibly of response to kinase inhibitors.


eRegTime, Efficiency of Health Information Management Using an Electronic Registry for Maternal and Child Health: Protocol for a Time-Motion Study in a Cluster Randomized Trial.
Paper-based routine health information systems often require repetitive data entry. In the West Bank, the primary health care system for maternal and child health was entirely paper-based, with care providers spending considerable amounts of time maintaining multiple files and client registers. As part of the phased national implementation of an electronic health information system, some of the primary health care clinics are now using an electronic registry (eRegistry) for maternal and child health. The eRegistry consists of client-level data entered by care providers at the point-of-care and supports several digital health interventions that are triggered by the documented clinical data, including guideline-based clinical decision support and automated public health reports. The aim of the eRegTime study is to investigate whether the use of the eRegistry leads to changes in time-efficiency in health information management by the care providers, compared with the paper-based systems. This is a substudy in a cluster randomized controlled trial (the eRegQual study) and uses the time-motion observational study design. The primary outcome is the time spent on health information management for antenatal care, informed and defined by workflow mapping in the clinics. We performed sample size estimations to enable the detection of a 25% change in time-efficiency with a 90% power using an intracluster correlation coefficient of 0.1 and an alpha of .05. We observed care providers for full workdays in 24 randomly selected primary health care clinics-12 using the eRegistry and 12 still using paper. Linear mixed effects models will be used to compare the time spent on health information management per client per care provider. Although the objective of the eRegQual study is to assess the effectiveness of the eRegistry in improving quality of antenatal care, the results of the eRegTime study will contribute to process evaluation, supplementing the findings of the larger trial. Electronic health tools are expected to reduce workload for the care providers and thus improve efficiency of clinical work. To achieve these benefits, the implementation of such systems requires both integration with existing workflows and the creation of new workflows. Studies assessing the time-efficiency of electronic health information systems can inform policy decisions for implementations in resource-limited low- and middle-income settings. DERR1-10.2196/13653.


Computer classification of nonproliferative diabetic retinopathy.
To propose methods for computer grading of the severity of 3 early lesions, namely, hemorrhages and microaneurysms, hard exudates, and cotton-wool spots, and classification of nonproliferative diabetic retinopathy (NPDR) based on these 3 types of lesions. Using a computer diagnostic system developed earlier, the number of each of the 3 early lesions and the size of each lesion in the standard photographs were determined. Computer classification criteria were developed for the levels of individual lesions and for NPDR. Evaluation of the criteria was performed using 430 fundus images with normal retinas or any degree of retinopathy and 361 fundus images with no retinopathy or the 3 early lesions only. The results were compared with those of the graders at the University of Wisconsin Ocular Epidemiology Reading Center and an ophthalmologist. Agreement rates in the classification of NPDR between the computer system and human experts. In determining the severity levels of individual lesions, the agreement rates between the computer system and the reading center were 82.6%, 82.6%, and 88.3% using the 430 images and 85.3%, 87.5%, and 93.1% using the 361 images, respectively, for hemorrhages and microaneurysms, hard exudates, and cotton-wool spots. When the "questionable" category was excluded, the corresponding agreement rates were 86.5%, 92.3%, and 91.0% using the 430 images and 89.7%, 96.3%, and 97.4% using the 361 images. In classifying NPDR, the agreement rates between the computer system and the ophthalmologist were 81.7% using the 430 images and 83.5% using the 361 images. The proposed criteria for computer classification produced results that are comparable with those provided by human experts. With additional research, this computer system could become a useful clinical aid to physicians and a tool for screening, diagnosing, and classifying NPDR.


Higher prevalence of irritable bowel syndrome and greater gastrointestinal symptoms in obsessive-compulsive disorder.
Anxiety and mood symptoms often co-occur with gastrointestinal problems, such as irritable bowel syndrome (IBS). The extent to which these relate to Obsessive-Compulsive Disorder (OCD) is unclear, despite anxiety being a prominent symptom of this disorder. The purpose of this analysis was to examine gastrointestinal symptoms in unmedicated, non-depressed adult OCD patients compared to age- and sex-matched community controls. Twenty-one OCD patients and 22 controls were recruited from the community (Hamilton, ON, Canada) and enrolled in this cross-sectional study. In addition to a standardized psychiatric assessment, participants completed clinician- and self-rated psychiatric and gastrointestinal symptom severity measures. Presence of IBS was assessed using Rome III criteria. Gastrointestinal symptom severity (GSRS total; OCD = 8.67 ± 6.72 vs. controls = 2.32 ± 2.12) and prevalence of IBS (OCD = 47.6%; Controls = 4.5%) was higher in OCD patients than in controls. A comparison of OCD patients based on IBS status revealed greater depressive symptom severity (total MADRS: 12.60 ± 1.89 vs 6.91 ± 2.77), p < 0.001) among those with IBS. High prevalence and severity of gastrointestinal symptoms may be an important clinical consideration when treating OCD patients. More specifically, assessment of IBS and gastrointestinal symptoms may be useful when considering pharmacotherapeutic treatments options for patients. Given the high comorbidity noted with IBS, a disorder of the "gut-brain axis", results may suggest a shared pathophysiological mechanism between psychiatric and gastrointestinal disorders which should be explored in future research.


Test of a trust and confidence model in the applied context of electromagnetic field (EMF) risks.
Trust is an important factor in risk management. There is little agreement among researchers, however, on how trust in risk management should be studied. Based on a comprehensive review of the trust literature a "dual-mode model of social trust and confidence" is proposed. Trust and confidence are separate but, under some circumstances, interacting sources of cooperation. Trust is based on value similarity, and confidence is based on performance. According to our model, judging similarity between an observer's currently active values and the values attributed to others determines social trust. Thus, the basis for trust is a judgment that the person to be trusted would act as the trusting person would. Interpretation of the other's performance influences confidence. Both social trust and confidence have an impact on people's willingness to cooperate (e.g., accept electromagnetic fields or EMF in the neighborhood). The postulated model was tested in the applied context of EMF risks. Structural equation modeling procedures and data from a random sample of 1,313 Swiss citizens between 18 and 74 years old were used. Results indicated that after minor modifications the model explained the data very well. In the applied context of EMF risks, both trust and confidence had an impact on cooperation. Results suggest that the dual-mode model of social trust and confidence could be used as a common framework in the field of trust and risk management. Practical implications of the results are discussed.


A monoclonal antibody to the insect prothoracicotropic hormone.
The prothoracicotropic hormone (PTTH) is an insect cerebral peptide that stimulates the prothoracic glands to produce the steroid hormone ecdysone thus initiating molting and metamorphosis. "Big" PTTH, one of several molecular forms of the neurohormone, was isolated from brains of the tobacco hornworm Manduca sexta, and fractionated by high-pressure liquid chromatography (HPLC) for use in antibody production. A murine polyclonal antiserum and a monoclonal antibody (MAb) have been generated using this highly purified preparation of big PTTH. Antisera and hybridoma supernatants were screened with an indirect, brain whole-mount immunocytological assay, and antibody specificity was confirmed by immunocytological, ELISA, and functional criteria. In brain whole-mount preparations, the MAb (A2H5) and antiserum specifically immunostained the lateral protocerebral neurosecretory cells (L-NSC III), the prothoracicotropes, which produce PTTH. This immunostaining was blocked by preadsorbing the antibodies with big PTTH. Analysis of the elution of HPLC-fractionated big PTTH with an in vitro bioassay for the neurohormone and an ELISA employing the A2H5 MAb resulted in peaks of activity that were superimposable. Finally, the antiserum and A2H5 MAb inhibited big PTTH activation of the prothoracic glands to synthesize ecdysone in the in vitro bioassay for the neurohormone. With these specific antibodies, the organization of the PTTH neuroendocrine axis has been defined. It is now evident that both of the peptidergic neurons that comprise the L-NSC III are prothoracicotropes, and that the corpora allata are the neurohemal organs for the release of big PTTH into the hemolymph. This study indicates that these specific antibodies will be useful in investigations of numerous aspects of the biology of this cerebral neuroendocrine axis.


Full disclosure: telling patients when not being a research subject is a good choice.
Informed consent to participation in research generally requires giving a person information about the alternatives to being in the research study. It is quite common, however, for research subjects not to be given one particularly significant piece of information: the possibility of obtaining the "new" treatment being studied directly from a doctor without participating in the study. Since many people enroll in studies precisely to get such a new treatment, they frequently would prefer that option--which guarantees them that new treatment--to enrolling in a study where there is only a 50% chance of getting the new treatment. This issue becomes more complicated in the context of pediatric oncology research, since physician-researchers in this field have entered into a unique informal agreement not to offer such new treatments outside of research studies. That agreement, which in effect forces physicians to behave in a manner that subordinates the well-being of some of their current patients to that of future patients, is ethically and legally questionable.


Adiabaticity of the proton-coupled electron-transfer step in the reduction of superoxide effected by nickel-containing superoxide dismutase metallopeptide-based mimics.
Nickel-containing superoxide dismutases (NiSODs) are bacterial metalloenzymes that catalyze the disproportionation of O2(-). These enzymes take advantage of a redox-active nickel cofactor, which cycles between the Ni(II) and Ni(III) oxidation states, to catalytically disprotorptionate O2(-). The Ni(II) center is ligated in a square planar N2S2 coordination environment, which, upon oxidation to Ni(III), becomes five-coordinate following the ligation of an axial imidazole ligand. Previous studies have suggested that metallopeptide-based mimics of NiSOD reduce O2(-) through a proton-coupled electron transfer (PCET) reaction with the electron derived from a reduced Ni(II) center and the proton from a protonated, coordinated Ni(II)-S(H(+))-Cys moiety. The current work focuses on the O2(-) reduction half-reaction of the catalytic cycle. In this study we calculate the vibronic coupling between the reactant and product diabatic surfaces using a semiclassical formalism to determine if the PCET reaction is proceeding through an adiabatic or nonadiabatic proton tunneling process. These results were then used to calculate H/D kinetic isotope effects for the PCET process. We find that as the axial imidazole ligand becomes more strongly associated with the Ni(II) center during the PCET reaction, the reaction becomes more nonadiabatic. This is reflected in the calculated H/D KIEs, which moderately increase as the reaction becomes more nonadiabatic. Furthermore, the results suggest that as the axial ligand becomes less Lewis basic the observed reaction rate constants for O2(-) reduction should become faster because the reaction becomes more adiabatic. These conclusions are in-line with experimental observations. The results thus indicate that variations in the axial donor's ability to coordinate to the nickel center of NiSOD metallopeptide-based mimics will strongly influence the fundamental nature of the O2(-) reduction process.


Primary and secondary Toxoplasma gondii infection in normal and feline immunodeficiency virus-infected cats.
Normal and asymptomatic feline immunodeficiency virus (FIV)-infected adult cats were inoculated orally with Toxoplasma gondii tissue cysts to assess differences in clinical disease, T. gondii serologic test results, hematologic results, and oocyst shedding. There was no difference between FIV-naive and FIV-infected cats in terms of clinical illness and duration of oocyst shedding following primary exposure. Both groups of cats developed significant decreases in neutrophil counts following primary inoculation with T. gondii; FIV-infected cats that were neutropenic prior to inoculation with T. gondii developed the most profound decreases in neutrophil numbers. Both FIV-naive and FIV-infected cats became lymphopenic during acute T. gondii infection; however, only FIV-naive cats developed lymphocytosis in the recovery stage. FIV-infected cats had lower total CD4+ and higher total CD8+ T-lymphocyte counts than FIV-naive cats prior to inoculation with T. gondii, but changes in these lymphocyte subsets were similar between groups of cats during the first several weeks after inoculation. Toxoplasma gondii infection had neither an ameliorating nor enhancing effect on T-lymphocyte subset abnormalities in FIV-infected cats during acute or chronic infection. Both groups of cats developed comparable levels of T. gondii-specific IgM and IgG antibodies and T. gondii antigen-specific lymphocyte blastogenic responses following primary inoculation. Both groups of cats were fed T. gondii tissue cysts 66 wk following primary exposure and both groups were solidly immune as evidenced by a lack of oocyst shedding and only minor changes in IgM but not IgG antibodies.


A small medical group's journey toward total quality management.
Steven M. Shufro, executive director of Concord Hillside Medical Associates, in Concord, Mass., documents the first year of the group's implementation of a quality program and what the results were. He includes a look at the organizational context of the group, the development of the program and how the Harvard Community Health Plan, the largest pre-paid HMO in New England, assisted them.


Correlation of putative iron content as represented by changes in R2* and phase with age in deep gray matter of healthy adults.
To establish a correlation between putative iron content using susceptibility weighted imaging (SWI) phase and T2* weighted magnitude values in the basal ganglia and the thalamus as a function of age in healthy human brains. One hundred healthy adults (range, 20-69 years; mean, 43 years) were evaluated for this study using a gradient echo sequence. The original magnitude and high pass filtered phase data were analyzed as proxy variables for iron content in the substantia nigra, red nucleus, globus pallidus, putamen, caudate nucleus, thalamus, and pulvinar thalamus. Each structure was broken into two parts, a high iron content region and a low iron content region. Both magnitude and phase data showed an increase in putative iron content with age. However, the high iron content region revealed two new pieces of information: both the average iron content per pixel and the area of high iron increased with age. Furthermore, significant increase in iron uptake as a function of age was found past the age of 40. A two region of interest analysis of iron is a much more sensitive means to evaluate iron content change over time. Contrary to the current belief that iron content increases level off with age, the putative iron deposition in the high iron content region is seen to increase with age.


Structural white matter changes in adolescents and young adults with maple syrup urine disease.
To get insight into the nature of magnetic resonance (MR) white matter abnormalities of patients with classic maple syrup urine disease (MSUD) under diet control. Ten patients with classic MSUD and one with a severe MSUD variant (mean age 21.5 ± 5.1 years) on diet and 11 age and sex-matched healthy subjects were enrolled. Apart from standard MR sequences, diffusion weighted images (DWI), diffusion tensor images (DTI), and magnetization transfer images (MT) were obtained and comparatively analyzed for apparent diffusion coefficient (ADC), tensor fractional anisotropy (FA) and MT maps in 11 regions of interest (ROI) within the white matter. In MSUD patients DWI, DTI and FA showed distinct signal changes in the cerebral hemispheres, the dorsal limb of internal capsule, the brain stem and the central cerebellum. Signal intensity was increased in DWI with a reduced ADC and decreased values for FA. MT did not reveal differences between patients and control subjects. Signal abnormalities in the white matter of adolescents and young adults under diet control may be interpreted as consequence of structural alterations like dysmyelination. The reduced ADC and FA in the white matter with preserved MT indicate a reduction in fiber tracks.


Design and analysis of an original powered foot clearance creator mechanism for walking in patients with spinal cord injury.
The aim of this study was to assess the performance of an original powered foot clearance creator (PFCC) mechanism worn in conjunction with an isocentric reciprocal gait orthosis (IRGO) and evaluate its effect on trunk compensatory movements and spatiotemporal parameters in nine healthy subjects. A PFCC motorized mechanism was designed that incorporated twin sole plates, the movements of which enabled increased toe to floor clearance during swing phase. A prototype was constructed in combination with an IRGO, and hence was re-named as an IRGO-PFCC orthosis. The effects of IRGO-PFCC usage on the spatiotemporal parameters and trunk compensatory movements during walking were then analyzed under two conditions, firstly with the PFCC 'active' i.e., with the motorized device functioning, and secondly inactive, where floor clearance was standard. Ambulating with IRGO-PFCC orthosis resulted in reduction in the spatiotemporal parameters of gait (speed of walking, cadence and stride length) in nine healthy subjects. Walking with IRGO-PFCC orthosis led to significant differences in lateral (p = .007) and vertical (p = .008) trunk compensatory movements. In other words, through using IRGO-PFCC orthosis, the lateral and vertical trunk compensatory movements decreased by 51.32% and 42.7%, respectively. An adapted PFCC mechanism, with a relatively small motor and power supply could effectively increase toe to floor clearance during swing phase and thereby decrease trunk compensatory motions and potentially improve energy consumption. Implications for rehabilitations •The High rejection rates of reciprocal gait orthoses are related to the increasing in energy expenditure and burden loads on the upper limb joints during walking following trunk compensatory movements.•An original powered foot clearance creator mechanism was designed and constructed to assisting floor clearance capability and reduce trunk compensatory movements in subjects with spinal cord injury during swing phase of gait.•This original powered foot clearance creator mechanism by using moveable soleplates and motorized actuation could decrease the trunk compensatory motions during the ambulation of nine healthy subjects.•More experiments are needed to investigate this mechanism on trunk compensatory movements of SCI subjects.


Molecular analysis of the gat genes from Escherichia coli and of their roles in galactitol transport and metabolism.
In enteric bacteria, the hexitol galactitol (Gat) (formerly dulcitol) is taken up through enzyme II (II(Gat)) of the phosphoenolpyruvate-dependent phosphotransferase system (PTS), and accumulated as galactitol 1-phosphate (Gat1P). The gat genes involved in galactitol metabolism have been isolated from the wild-type isolate Escherichia coli EC3132 and cloned on a 7.8-kbp PstI DNA fragment. They comprise six complete open reading frames and one truncated open reading frame in the order gatYZABCDR'. The genes gatABC code for the proteins GatA (150 residues) and GatB (94 residues), which correspond to the hydrophilic domains IIA(Gat) and IIB(Gat), and GatC, which represents a membrane-bound transporter domain IIC(Gat) (35 kDa, 427 residues). The three polypeptides together constitute a II(Gat) of average size (671 residues). Gene gatD codes for a Gat1P-specific NAD-dependent dehydrogenase (38 kDa, 346 residues), gatZ codes for a protein (42 kDa, 378 residues) of unknown function, and gatY (31 kDa, 286 residues) codes for a D-tagatose-1,6-bisphosphate aldolase with similarity to other known ketose-bisphosphate aldolases. The truncated gatR' gene, whose product shows similarity to the glucitol repressor GutR, closely resembles a gatR gene fragment from E. coli K-12. The gat genes map in both organisms at similar positions, in E. coli K-12, where they are transcribed counterclockwise at precisely 46.7 min or 2,173 to 2,180 kbp. The genes are expressed constitutively in both strains, probably due to a mutation(s) in gatR. Transcription initiation sites for the gatYp and the gatRp promoters were determined by primer extension analysis.


Secondary Structural Change Can Occur Diffusely and Not Modularly during Protein Folding and Unfolding Reactions.
A major goal of protein folding studies is to understand the structural basis of the coupling between stabilizing interactions, which leads to cooperative conformational change. The goal is challenging because of the difficulty in simultaneously measuring global cooperativity by determining population distributions of the conformations present, and the structures of these conformations. Here, hydrogen exchange (HX) into the small protein monellin was carried out under conditions where structure-opening is rate limiting for most backbone amide sites. Detection by mass spectrometry allowed characterization of not only segment-specific structure-opening rates but also the cooperativity of unfolding of the different secondary structural segments of the protein. The segment-specific pattern of HX reveals that the backbone hydrogen-bonding network disassembles in a structurally diffuse, asynchronous manner. A comparison of the site-specific transient opening rates of secondary and tertiary structure in the protein provides a structural rationale for the observation that unfolding is hierarchical and describable by exponential kinetics, despite being diffuse. Since unfolding was studied in native conditions, the sequence of events during folding in the same conditions will be the reverse of the sequence of events observed during unfolding. Hence, the formation of secondary structural units during folding would also occur in a non-cooperative, diffuse, and asynchronous manner.


Enrichment and low-level determination of glyphosate, aminomethylphosphonic acid and glufosinate in drinking water after cleanup by cation exchange resin.
For the determination of glyphosate, aminomethylphosphonic acid and glufosinate in drinking water, different procedures of enrichment and cleanup were examined using anion exchange or SPE. In many cases interactions of, e.g. alkaline earth metal ions especially calcium could be observed during enrichment and cleanup resulting in loss of analytes. For that reason, a novel cleanup and enrichment procedure for the determination of these phosphonic acid herbicides has been developed in drinking water using cation-exchange resin. In summary, the cleanup procedure with cation-exchange resin developed in this study avoids interactions as described above and is applicable to calcium-rich drinking water samples. After derivatization with 9-fluorenylmethylchloroformate followed by LC with fluorescence detection, LOD of 12, 14 and 12 ng/L and mean recoveries from real-world drinking water samples of 98+/-9, 100+/-16 and 101+/-11% were obtained for glyphosate, aminomethylphosphonic acid and glufosinate, respectively. The low LODs and the high precision permit the analysis of these phosphonic acid herbicides according to the guidelines of the European Commission.


The application value of continuous nursing for home oxygen therapy of patients in the stable phase of chronic obstructive pulmonary disease.
To analyze the application value of continuous nursing in improving the effects of home oxygen therapy for patients in the stable phase of chronic obstructive pulmonary disease (COPD). Patients in the stable phase of COPD (n=106) were selected and divided into the control group and observation group based on parity digit of their admission number. There were 53 cases in each group. The patients in the control group received COPD health education at discharge, while the observation group received continuous nursing. The effect of home oxygen therapy in both groups after 3 months was compared. The compliance in the observation group for home oxygen therapy was significantly higher than that in the control group. Blood gas analysis and various indicators of pulmonary function in the control group at follow-up visits were not changed compared with those before. In contrast, partial pressure of blood oxygen and blood oxygen saturation of the observation group were lower than those before discharge. With the increasing partial pressure of carbon dioxide in arterial blood, the indicators of pulmonary function became lower than before. Comparing the various indexes between both groups at follow-up visits, the differences were statistically significant (p<0.05). The self-care ability and quality of life scores of patients in the observation group were higher than those of the control group, and the differences were statistically significant (p<0.05). By establishing health records and network platforms, continuous nursing can provide continuous health education and supervision for patients with COPD, which can effectively improve oxygen therapy compliance, self-care ability and quality of life. It has good application and promotional value.


[Innovation, quality and economic efficacy of competitive health care--contribution to the "Healthy North Rhine-Westphalia" Project].
This is a report on what the Provincial Government of North Rhine Westphalia, the most densely populated area in Germany, has been doing to ensure that the various health establishments (such as, for example, hospitals, nursing homes, rehabilitation clinics, and so on) engaged in serving the public, shall act in solidarity jointly and severally in striving for maximum innovation, quality and efficiency while observing all the rules of competitive fairness. This approach was initiated by the Federal German government in 1993 by promulgating a law reforming the structural setup of all organisations engaged in health service work. From 1996 onward these institutions will be operating within the framework of rules ensuring mutual solidarity on a competitive basis. The general trend is to increase self-administration and a wider scope of activities and creative initiative based on imagination and economy, the latter becoming increasingly imperative to avoid wasteful working. In other words: By encouraging competition directed at a maximum of innovation, quality and economy, the main targets of public health policy will be finally within reach: to maintain the quality standards of public health services, to promote general access to these services, and also to provide a sound financial basis for them.


A Self-Calibration Stitching Method for Pitch Deviation Evaluation of a Long-Range Linear Scale by Using a Fizeau Interferometer.
An interferometric self-calibration method for the evaluation of the pitch deviation of scale grating has been extended to evaluate the pitch deviation of the long-range type linear scale by utilizing the stitching interferometry technique. Following the previous work, in which the interferometric self-calibration method was proposed to assess the pitch deviation of the scale grating by combing the first-order diffracted beams from the grating, a stitching calibration method is proposed to enlarge the measurement range. Theoretical analysis is performed to realize the X-directional pitch deviation calibration of the long-range linear scale while reducing the second-order accumulation effect by canceling the influence of the reference flat error in the sub-apertures' measurements. In this paper, the stitching interferometry theory is briefly reviewed, and theoretical equations of the X-directional pitch deviation stitching are derived for evaluation of the pitch deviation of the long-range linear scale. Followed by the simulation verification, some experiments with a linear scale of 105 mm length from a commercial interferential scanning-type optical encoder are conducted to verify the feasibility of the self-calibration stitching method for the calibration of the X-directional pitch deviation of the linear scale over its whole area.


Global dynamics of a stochastic neuronal oscillator.
Nonlinear oscillators have been used to model neurons that fire periodically in the absence of input. These oscillators, which are called neuronal oscillators, share some common response structures with other biological oscillations such as cardiac cells. In this study, we analyze the dependence of the global dynamics of an impulse-driven stochastic neuronal oscillator on the relaxation rate to the limit cycle, the strength of the intrinsic noise, and the impulsive input parameters. To do this, we use a Markov operator that both reflects the density evolution of the oscillator and is an extension of the phase transition curve, which describes the phase shift due to a single isolated impulse. Previously, we derived the Markov operator for the finite relaxation rate that describes the dynamics of the entire phase plane. Here, we construct a Markov operator for the infinite relaxation rate that describes the stochastic dynamics restricted to the limit cycle. In both cases, the response of the stochastic neuronal oscillator to time-varying impulses is described by a product of Markov operators. Furthermore, we calculate the number of spikes between two consecutive impulses to relate the dynamics of the oscillator to the number of spikes per unit time and the interspike interval density. Specifically, we analyze the dynamics of the number of spikes per unit time based on the properties of the Markov operators. Each Markov operator can be decomposed into stationary and transient components based on the properties of the eigenvalues and eigenfunctions. This allows us to evaluate the difference in the number of spikes per unit time between the stationary and transient responses of the oscillator, which we show to be based on the dependence of the oscillator on past activity. Our analysis shows how the duration of the past neuronal activity depends on the relaxation rate, the noise strength, and the impulsive input parameters.


[Analysis of aldicarb and its metabolites in ginger using ultra performance liquid chromatography-tandem mass spectrometry coupled with multiplug filtration clean up with multiwalled carbon nanotubes].
A simple and rapid pretreatment procedure was developed for the simultaneous determination of aldicarb and its metabolites, aldicarb sulfone and aldicarb sulfoxide in ginger. The samples were extracted with acetonitrile, and then cleaned up with multiplug filtration using multiwalled carbon nanotubes (MWCNTS). The eluate was dried with nitrogen gas at room temperature, and redissolved in an acetonitrile-water (5:95, v/v) mixture, then quantified by ultra performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) operated in positive multiple reaction monitoring (MRM) mode. A linear relationship was achieved in the range of 0.5 -200 microg/L for the peak areas to the mass concentrations of the target compounds with the linear correlation coefficients (r2) higher than 0.99. The recoveries at three spiked levels of 2, 20 and 200 microg/kg were in the range from 71.4% to 89.8% with the relative standard deviations (RSDs, n = 6) from 0.7% to 13.2% under the selected conditions. The limits of quantification (LOQ, S/N = 10) of aldicarb, aldicarb sulfone, and aldicarb sulfoxide in ginger were 1.0, 2.0 and 1.0 microg/kg, respectively. The results demonstrate that the developed method is rapid, cost-effective, and can meet the requirements of the multiple pesticide residue analysis. The method is applicable to determine aldicarb and its metabolites in ginger.


Defective regulation of the phenylalanine biosynthetic operon in mutants of the phenylalanyl-tRNA synthetase operon.
Among mutants of Escherichia coli resistant to p-fluorophenylalanine (PFP) were some with constitutive expression of the phenylalanine biosynthetic operon (the pheA operon). This operon is repressed in the wild type by phenylalanine. The mutation in three of these mutants mapped in the aroH-aroD region of the E. coli chromosome at 37 min. A plasmid bearing wild-type DNA from this region restored p-fluorophenylalanine sensitivity and wild-type repression of the pheA operon. Analysis of subclones of this plasmid and comparison of its restriction map with published maps indicated that the mutations affecting regulation of the pheA operon lie in the structural genes for phenylalanyl-tRNA synthetase, pheST, probably in pheS. Thus, the pheST operon has a role in the regulation of phenylalanine biosynthesis, the most likely being that wild-type phenylalanyl-tRNA synthetase maintains a sufficient intracellular concentration of Phe-tRNA(Phe) for attenuation of the pheA operon in the presence of phenylalanine. A revised gene order for the 37-min region of the chromosome is reported. Read clockwise, the order is aroD, aroH, pheT, and pheS.


Parent stress in the neonatal intensive care unit and the influence of parent and infant characteristics.
This study investigated the stress experienced by parents in the neonatal intensive care unit (NICU), the infant and parent characteristics that resulted in different stress responses, and the characteristics that were predictive of stress. The Parental Stress Scale: Neonatal Intensive Care Unit was used to measure the stress of 162 parents. A Parent/Infant Demographic sheet provided information for determining which characteristics resulted in different responses and which variables were stress predictors. The highest levels of stress experienced were in the relationship with baby-parental role area, and regarding how the baby looked and behaved. The infant characteristic of gestational age resulted in significantly different scores concerning the baby's appearance and behavior. Consistent predictors of stress were length of stay, extreme prematurity, and a cardiovascular diagnosis. Identifying the stressors parents experience can assist NICU therapists in intervention planning. Family-centered care that addresses stressors concerning their roles and their understanding of their infant should be emphasized.


[An improved method and its application for agricultural drought monitoring based on remote sensing].
From the viewpoint of land surface evapotranspiration, and by using the semi-empirical evapotranspiration model based on the Priestley-Taylor equation and the land surface temperature-vegetation index (LST-VI) triangle algorithm, the current monitoring technology of agricultural drought based on remote sensing was improved, and a simplified Evapotranspiration Stress Index (SESI) was derived. With the application of the MODIS land products from March to November in 2008 and 2009, the triangle algorithm modeling with three different schemes was constructed to calculate the SESI to monitor the agricultural drought in the plain areas of Beijing, Tianjin, and Hebei, in comparison with the Temperature Vegetation Dryness Index (TVDI). The results showed that SESI could effectively simplify the remote sensing drought monitoring method, and there was a good agreement between SESI and surface soil (10 and 20 cm depth) moisture content. Moreover, the performance of SESI was better in spring and autumn than in summer, and the SESI during different periods was more comparable than TVDI. It was feasible to apply the SESI to the continuous monitoring of a large area of agricultural drought.


Dislocation of tight junction proteins without F-actin disruption in inactive Crohn's disease.
Crohn's disease is associated with increased permeability of the intestinal barrier even in quiescent patients. Increased intestinal permeability may cause dysregulated immunological responses in the intestinal mucosa that leads to chronic intestinal inflammation. We have studied the expression of tight junction proteins (occludin and zonula occludens), alpha2-smooth muscle actin, TGF-beta with a cytoskeletal protein (F-actin) in the intestinal epithelium of patients with inflammatory bowel disease. Surgical samples were obtained from 6 controls (individuals without inflammatory bowel disease), 8 patients with ulcerative colitis and 7 patients with Crohn's disease. F-actin was visualized with fluorescein phalloidin. Tight junction proteins, alpha2 smooth muscle actin, and TGFbeta were visualized by the immunofluorescent method. Occludin and zonula occludens found in apical tight junctions in normal epithelium were dislocated to the basolateral position and in the lamina propria extracellular matrix in patients with Crohn's disease, while the structure of F-actin was maintained in inactive or minimally inflamed mucosa. TGF-beta positive inflammatory cells were increased in ulcerative colitis and Crohn's disease mucosa. Subepithelial myofibroblasts were constitutively found in controls, ulcerative colitis, and Crohn's disease mucosa. Latent dislocation of tight junction proteins, without disturbance of the cytoskeleton in the inactive mucosa of patients with Crohn's disease, may permit the invasion of gut antigens because the functional disruption of tight junctions could initiate an altered immune response.


Skeletal Muscle Density and Cognitive Function: A Cross-Sectional Study in Men.
We aimed to investigate cross-sectional associations between skeletal muscle density, a proxy measure for fatty infiltration into muscle, and cognition. Contributions from body fat mass, systemic inflammation and lifestyle were explored, as these factors have been identified in both muscle and cognitive deterioration. For 281 men (60-95 year) from the Geelong Osteoporosis Study, radial and tibial muscle density were measured using peripheral quantitative computed tomography. Body fat and appendicular lean mass were measured using dual-energy X-ray absorptiometry. Cognitive function was assessed for psychomotor function (DET), visual identification/attention (IDN), visual learning (OCL) and working memory (OBK) (CogState Brief Battery). Composite scores signified overall cognitive function (OCF). Higher scores represent poorer performance except for OCL and OCF. Regression analyses examined associations between muscle density and cognition; potential confounders included age, muscle cross-sectional area (CSA), body composition, lifestyle and serum markers of inflammation. Negative associations with age were evident for muscle density, all cognitive domains and OCF. Muscle density at both sites was positively associated with DET, OCL and OCF. After adjustment for age, the association persisted for DET (radius: B = - 0.006, p = 0.02; tibia: B = - 0.003, p = 0.04) and OCL (radius B = + 0.004, p = 0.02; tibia: B = + 0.005, p < 0.001). At the radius, further adjustment for serum TNF-α explained the association between muscle density (B = - 0.002, p = 0.66) and DET. Education and physical activity contributed to the model for radial muscle density and DET. There were no contributions from muscle CSA, appendicular lean mass, body fat mass, other markers of inflammation or other potential confounders. At the tibia, the association between muscle density and DET (B = - 0.003, p = 0.04) was independent of TNF-α. There was an age-adjusted association between muscle density and OCL at both sites (radius: B = + 0.004, p = 0.02; tibia: B = + 0.005, p < 0.001). None of the potential confounders contributed to the models. Muscle density was associated with cognitive function in the DET and OCL domains. However, there was little evidence that this was explained by inflammation or body fat mass. No associations were identified between muscle density and IDN or OBK.


Bullous eruption associated with scabies: evidence for scabetic induction of true bullous pemphigoid.
Some patients with scabies develop bullae concomitantly with, or subsequently after, the occurrence of scabetic lesions. Although several immunofluorescence studies have demonstrated immunoglobulin deposition in the basement membrane zone of bullous lesions, it remained unclear whether these antibodies are directed to bullous pemphigoid antigens. We clearly show that two scabetic patients with bullous eruptions had circulating antibodies against BP180 and/or BP230 as determined by Western blotting analysis. This is the first report to demonstrate that at least some of the bullous eruptions occurring in scabetics are true bullous pemphigoid.


Investigation of mcp1 as a quantitative trait gene for prion disease incubation time in mouse.
The genetic basis of prion disease incubation time is principally determined by polymorphisms in the prion protein gene, Prnp. However, it is now known that other genetic factors are important. Several quantitative trait loci (QTL) have been identified across the genome including a broad region of linkage on Mmu11. Monocyte chemoattractant protein 1 (MCP-1) maps to this region and has been associated with microglial activation and reduced survival in the ME7 mouse scrapie model of prion disease. We have identified 10 polymorphisms, 3 of which are nonsynonomous, in Mcp1 between "long" (CAST) and "short" (SJL or NZW) incubation-time mouse strains. Crosses between these strains and Mcp1(-/-) mice inoculated with the Chandler/RML mouse scrapie prion strain formed the basis of a quantitative complementation test. In these models loss of Mcp1 did not show an increase in incubation time suggesting that the effects of Mcp1 may be specific to the ME7 prion strain and that Mcp1 does not contribute to the QTL described on Mmu11.


Assessing the effects of wind farms on soil organic carbon.
Wind energy is considered one of the cleanest and most sustainable resources among renewable energy sources. However, several negative environmental impacts can be observed, unless suitable sites are selected for the establishment of wind farms. The aim of this study is to determine the change in the soil organic carbon (SOC) stock resulting from land cover changes that were caused by wind farm establishments in the Karaburun peninsula. Within the scope of the study, remote sensing and geographic information system technologies were utilized. Maximum likelihood algorithm, one of the supervised classification techniques, was used to classify the land cover, and Normalized Difference Vegetation Index (NDVI) analyses were performed to determine land cover changes. The findings were correlated with the "Turkey Soil Organic Carbon Project" data. As a result, depending on the establishment of wind farms in the Karaburun Peninsula, a total decrease of 18,330.57 tons of SOC in the study area between 2000 and 2019 was determined. It should be taken into consideration that besides many other negative effects (effects on human health, effects on the ecosystem, effects on animals, etc.), land cover changes caused by wind farms may indirectly cause important problems such as climate change. Recently, this situation shows that there is an important dilemma in terms of current implementations. Wind farms are the most invested renewable energy sources and alternative energy supply to fossil fuels in terms of preventing climate change. However, the results of this study have reviewed that lack of proper approaches and methods to establish wind farms may result in various problems such as physical, chemical, and biological degradations and an increase in the amount of atmospheric carbon. Consequently, the investments in renewable energy sources should be comprehensively reevaluated in terms of current technologies, quality in the scope of environmental impact assessment and strategic environmental assessment processes, legal regulations and national policies, long-term environmental costs, etc.


Regulation of androgen receptor mRNA expression in hamster facial motoneurons: differential effects of non-aromatizable and aromatizable androgens.
We have previously shown inherent sex differences in the levels of androgen receptor mRNA (AR mRNA) in hamster facial motor neurons (FMN). FMN of intact females contained approximately 50% less AR mRNA than their male counterparts. Gonadectomy in males down-regulated AR mRNA levels in FMN by approximately 50%, whereas no effects of gonadectomy were observed in females. Sex differences in the regulation of AR mRNA levels by exogenous testosterone propionate (TP) were also observed. In those studies, AR mRNA levels were up-regulated after 1 day of treatment with exogenous TP in FMN of gonadectomized (GDX) males and after 7 days in FMN of intact females, with no effects in GDX females. Since TP is aromatizable to estrogen, and given recent findings of transient expression of estrogen receptors (ER) in rodent FMN, the effects of dihydrotestosterone (DHT), a non-aromatizable form of the steroid, on AR mRNA expression in hamster FMN were examined in the present study. If testosterone (TES) were the active hormone regulating AR mRNA levels in FMN, DHT treatment should render a similar regulatory pattern as TP, but if metabolism of TES to estradiol plays a role in AR mRNA regulation, effects of the two treatments should differ. In situ hybridization and computerized image analysis were used to quantify the regulation of AR mRNA by DHT in individual FMN of hamsters of both sexes. Exogenous DHT was administered to intact and gonadectomized (GDX) male and female hamsters by implantation of one 10-mm Silastic capsule for 1, 2 or 7 days. AR mRNA levels were significantly up-regulated in intact females at all time points of DHT exposure, with no effects in GDX groups. These results differ from previous work using TP, in which a modest up-regulation in AR mRNA levels was observed in FMN of intact females only after 7 days. As with TP, DHT exposure gradually down-regulated AR mRNA levels in FMN of intact males. Thus, DHT only regulated AR mRNA levels in intact animals, with endogenous sources of estrogen available, but not in GDX animals, with endogenous estrogens reduced by gonadectomy. Taken together, these results substantiate our previous findings of sex differences in AR mRNA levels/regulation and suggest a synergism between estrogen and androgen in the regulation of AR mRNA levels in peripheral motor neurons.


Complex Extreme Sea Levels Prediction Analysis: Karachi Coast Case Study.
In this study, the analysis of the extreme sea level was carried out by using 10 years (2007-2016) of hourly tide gauge data of Karachi port station along the Pakistan coast. Observations revealed that the magnitudes of the tides usually exceeded the storm surges at this station. The main observation for this duration and the subsequent analysis showed that in June 2007 a tropical Cyclone "Yemyin" hit the Pakistan coast. The joint probability method (JPM) and the annual maximum method (AMM) were used for statistical analysis to find out the return periods of different extreme sea levels. According to the achieved results, the AMM and JPM methods erre compatible with each other for the Karachi coast and remained well within the range of 95% confidence. For the JPM method, the highest astronomical tide (HAT) of the Karachi coast was considered as the threshold and the sea levels above it were considered extreme sea levels. The 10 annual observed sea level maxima, in the recent past, showed an increasing trend for extreme sea levels. In the study period, the increment rates of 3.6 mm/year and 2.1 mm/year were observed for mean sea level and extreme sea level, respectively, along the Karachi coast. Tidal analysis, for the Karachi tide gauge data, showed less dependency of the extreme sea levels on the non-tidal residuals. By applying the Merrifield criteria of mean annual maximum water level ratio, it was found that the Karachi coast was tidally dominated and the non-tidal residual contribution was just 10%. The examination of the highest water level event (13 June 2014) during the study period, further favored the tidal dominance as compared to the non-tidal component along the Karachi coast.


Brainprint Recognition Based on the Stable SSVEP Space-Frequency Energy Distribution.
Brainprint recognition has received increasing attention in information security. Electroencephalography (EEG) signals measured under task-related or task-free conditions have been exploited as brain biometrics. However, what components make the uniqueness of one's brain signals remains unclear. In this study, we proposed an interpretable biomarker based on steady-state visual evoked potentials (SSVEP) signals for EEG biometric identification. Firstly, we recovered pure SSVEP components from EEG by a point-position equivalent reconstruction (PPER) method. Then, we calculated the distribution properties of SSVEP components in space and frequency. By using the uniform manifold approximation and projection, we reduced the distribution features to 2-dimensions, which shows the separability of the subjects. Lastly, we built a long short-term memory (LSTM) network to perform brainprint recognition on the SSVEP benchmark dataset. The average recognition accuracy can reach up to 98.33%. Our results demonstrate that the space-frequency energy feature of SSVEP is an effective and interpretable biomarker for brainprint recognition. This study provides a further understanding of the uniqueness of individual EEG signal, and facilitates its potential application for personal identification.


The Clinical Value of Autoantibodies in Rheumatoid Arthritis.
Rheumatoid arthritis (RA) is a highly heterogeneous syndrome in terms of clinical presentation, progression, and response to therapy. In such a complicated context, the identification of disease-related biomarkers would be undoubtedly helpful in assisting tailored approaches for every patient. Despite remarkable efforts, however, progress in new biomarker development and validation is dramatically slow. At present, none of the candidate genetic, cellular, or molecular biomarker has yet surpassed the clinical value of RA-specific autoantibodies, including rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA). Rather, recent years have witnessed significant advancements in our understanding of the multiple roles that RF and ACPA play in RA pathophysiology. This has helped clarifying the mechanistic basis of the clinical associations of autoantibodies in RA. In this short review, we will briefly summarize the effector functions of RF and ACPA, and analyse how autoantibodies may help subclassifying RA patients in terms of clinical presentation and response to therapy.


Clot strength is negatively associated with ambulatory function in patients with peripheral artery disease and intermittent claudication.
Peripheral artery disease (PAD) is associated with exercise impairment and greater thrombotic risk. We investigated whether clot formation and platelet aggregation assessed by thromboelastography and light-transmission aggregometry correlate with the severity of symptomatic PAD assessed by ambulatory function measures. We studied 40 symptomatic patients with PAD in whom severity of disease was assessed using ankle-brachial index, peak walking time (PWT), claudication onset time, peak oxygen uptake, daily ambulatory activity, and walking impairment questionnaire (WIQ) scores. Clot strength correlated negatively with peak oxygen uptake, PWT, WIQ distance, and stair-climbing scores. Time to clot formation did not correlate with exercise parameters. Platelet aggregation was negatively correlated with WIQ distance score and was positively correlated with PWT and peak oxygen uptake. In conclusion, clot strength and platelet aggregation correlated with objective and self-perceived ambulatory measures. Patients with PAD having more severe walking impairment may be likely to form stronger clots.


Pros and Cons of Audience Response Systems in the Education of Health Professionals.
This article was migrated. The article was marked as recommended. Well over 1000 articles have been written on the subject of Audience Response Systems in the education of health professionals. These studies have involved the students at the undergraduate, graduate and continuing professional education levels. From the articles found, a subset of over 120 articles of ARS use in health professional education was reviewed. A holistic view of the results in these studies showed that there are clear benefits and drawbacks to ARS use from the perspective of the students and teachers. Benefits were found to fit ten (10) distinct categories while drawbacks fit into six (6) discrete categories. This paper summarizes and discusses the benefits (i.e. pros) and drawbacks (i.e. cons) of the use of ARS in the educational process of health professionals.


Peripheral reconstruction when adequate saphenous vein is lacking.
For arterial reconstructions below the inguinal ligament without the use of autologous saphenous vein a critical question is the location of the distal anastomosis. In femoropopliteal bypass above the knee either umbilical vein grafts or PTFE grafts can be used with reasonable success. Externally supported Dacron grafts have given excellent results in some series. Endarterectomy and patch graft angioplasty may be used when implantation of foreign material should be avoided. Some investigators have found the umbilical vein graft superior to PTFE grafts for below knee reconstructions. For leg artery reconstructions we feel that at least a segment of autologous vein is needed to get a reconstruction with a satisfactory patency rate.


Ignorance of hedonic adaptation to hemodialysis: a study using ecological momentary assessment.
Healthy people generally underestimate the self-reported well-being of people with disabilities and serious illnesses. The cause of this discrepancy is in dispute, and the present study provides evidence for 2 causes. First, healthy people fail to anticipate hedonic adaptation to poor health. Using an ecological momentary assessment measure of mood, the authors failed to find evidence that hemodialysis patients are less happy than healthy nonpatients are, suggesting that they have largely, if not completely, adapted to their condition. In a forecasting task, healthy people failed to anticipate this adaptation. Second, although controls understated their own mood in both an estimation task and a recall task, patients were quite accurate in both tasks. This relative negativity in controls' estimates of their own moods could also contribute to their underestimation of the moods and overall well-being of patients.


Post-vaccine COVID-19 in patients with multiple sclerosis or neuromyelitis optica.
Recent studies suggested that anti-CD20 and fingolimod may be associated with lower anti-spike protein-based immunoglobulin-G response following COVID-19 vaccination. We evaluated if COVID-19 occurred despite vaccination among patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), using the COVISEP registry. We report 18 cases of COVID-19 after two doses of BNT162b2-vaccination, 13 of which treated with anti-CD20 and four with fingolimod. COVID-19 severity was mild. These results reinforce the recommendation for a third COVID-19 vaccine dose among anti-CD20 treated patients and stress the need for a prospective clinical and biological study on COVID-19 vaccine efficacy among MS and NMO patients.


Generative-based airway and vessel morphology quantification on chest CT images.
Accurately and precisely characterizing the morphology of small pulmonary structures from Computed Tomography (CT) images, such as airways and vessels, is becoming of great importance for diagnosis of pulmonary diseases. The smaller conducting airways are the major site of increased airflow resistance in chronic obstructive pulmonary disease (COPD), while accurately sizing vessels can help identify arterial and venous changes in lung regions that may determine future disorders. However, traditional methods are often limited due to image resolution and artifacts. We propose a Convolutional Neural Regressor (CNR) that provides cross-sectional measurement of airway lumen, airway wall thickness, and vessel radius. CNR is trained with data created by a generative model of synthetic structures which is used in combination with Simulated and Unsupervised Generative Adversarial Network (SimGAN) to create simulated and refined airways and vessels with known ground-truth. For validation, we first use synthetically generated airways and vessels produced by the proposed generative model to compute the relative error and directly evaluate the accuracy of CNR in comparison with traditional methods. Then, in-vivo validation is performed by analyzing the association between the percentage of the predicted forced expiratory volume in one second (FEV1%) and the value of the Pi10 parameter, two well-known measures of lung function and airway disease, for airways. For vessels, we assess the correlation between our estimate of the small-vessel blood volume and the lungs' diffusing capacity for carbon monoxide (DLCO). The results demonstrate that Convolutional Neural Networks (CNNs) provide a promising direction for accurately measuring vessels and airways on chest CT images with physiological correlates.


The periplasmic modifier protein for methanol dehydrogenase in the methylotrophs Methylophilus methylotrophus and Paracoccus denitrificans.
A modifier protein (M-protein), which increases the affinity of methanol dehydrogenase (MDH) for alcohols but decreases its affinity for formaldehyde, has been partially purified from Methylophilus methylotrophus and Paracoccus denitrificans. Analysis was complicated by non-protein factors in bacterial extracts that are able to mimic M-protein in one of its functions-that of increasing the activity of MDH with butane-1,3-diol in the dye-linked assay system. The 67 kDa polypeptide, previously identified as a subunit of the M-protein, is an unrelated cytoplasmic protein. The M-protein is exclusively periplasmic and is a multimeric protein with subunits of 45 kDa. The M-protein is active in the 'physiological' assay system with the specific cytochrome c electron acceptor for MDH, lowering its affinity for formaldehyde. It has its maximum effect when the ratio of M-protein:MDH is 1:5 but its concentration in the periplasm is much lower than 20% of that of MDH.


Amino group in Leptothrix sheath skeleton is responsible for direct deposition of Fe(III) minerals onto the sheaths.
Leptothrix species produce microtubular organic-inorganic materials that encase the bacterial cells. The skeleton of an immature sheath, consisting of organic exopolymer fibrils of bacterial origin, is formed first, then the sheath becomes encrusted with inorganic material. Functional carboxyl groups of polysaccharides in these fibrils are considered to attract and bind metal cations, including Fe(III) and Fe(III)-mineral phases onto the fibrils, but the detailed mechanism remains elusive. Here we show that NH2 of the amino-sugar-enriched exopolymer fibrils is involved in interactions with abiotically generated Fe(III) minerals. NH2-specific staining of L. cholodnii OUMS1 detected a terminal NH2 on its sheath skeleton. Masking NH2 with specific reagents abrogated deposition of Fe(III) minerals onto fibrils. Fe(III) minerals were adsorbed on chitosan and NH2-coated polystyrene beads but not on cellulose and beads coated with an acetamide group. X-ray photoelectron spectroscopy at the N1s edge revealed that the terminal NH2 of OUMS1 sheaths, chitosan and NH2-coated beads binds to Fe(III)-mineral phases, indicating interaction between the Fe(III) minerals and terminal NH2. Thus, the terminal NH2 in the exopolymer fibrils seems critical for Fe encrustation of Leptothrix sheaths. These insights should inform artificial synthesis of highly reactive NH2-rich polymers for use as absorbents, catalysts and so on.


Multicenter evaluation of a rapid and convenient method for determination of cytomegalovirus immunoglobulin G avidity.
An easy, rapid, and reproducible test to distinguish residual cytomegalovirus (CMV) immunoglobulin M (IgM) antibodies from antibodies produced in primary infection could be useful, especially for pregnant women. The CMV avidity of IgG antibodies with the VIDAS automated enzyme-linked fluorescent assay and 6 M urea was evaluated in a multicenter study to differentiate between primary CMV infections and past infections or reactivations. A total of 416 serum specimens were tested: 159 specimens were from follow-up of primary infections, and 257 were from past infections. All of the specimens from primary infections collected within 4 months (17 weeks) after the onset of the infection had an avidity index lower than 0.8. An avidity index higher than 0.8 excludes a recent primary infection of less than 4 months. However, an avidity index higher than 0.8 cannot confirm all past infections, since 48 specimens (18%) from past infections had an avidity index lower than 0.8 (between 0.5 and 0.8). The exclusion capacity could be improved (96.9%) by using a cutoff of 0.7, but this index would decrease the specificity of the technique, since the avidity index was found to be between 0.7 and 0.8 in two patients with recent primary infection. All specimens from primary infections obtained more than 4 months after the onset of infection had an avidity index more than 0.2. In this study, an avidity index less than 0.2 confirms the presence of a recent primary infection of less than 4 months. The VIDAS CMV IgG avidity test is a rapid, reproducible test with very good performance.


NanoTPOT: Enhanced Sample Preparation for Quantitative Nanoproteomic Analysis.
With the ever-growing need for protein-level understanding in pathological research, proteomics researchers thrive to examine detailed proteome dynamics using crucial, yet often limited, primary and clinical samples. Aside from mass spectrometer instrumentation advancement, a single-tube-based high-throughput sample processing workflow is imperative to ensure sensitive, quantitative, and reproducible protein analysis for these increasingly sophisticated studies. Leveraging the benefits of an acid-cleavable detergent, RapiGest SF Surfactant (Waters Corporation), we developed and optimized a nanoproteomic workflow that we termed Nanogram TMT Processing in One Tube (NanoTPOT). Through the assessment of proteolytic digestion, tandem mass tag (TMT) labeling, online and offline fractionation strategies, our optimized workflow effectively eliminated the need for sample desalting and enabled compatible sample processing for mass spectrometry analysis. We further applied the NanoTPOT workflow to examine cellular response to stress caused by dithiothreitol in HeLa cells, where we identified and quantified 6935 and 5474 proteins in TMT 10-plex experiments with one microgram of lysate protein and 2000 sorted HeLa cells (roughly half microgram lysate protein) in each channel, respectively. Our workflow has been proven to be an effective alternative for current nanoproteomic sample processing to minimize sample loss in biological and clinical applications.


[Conformational transitions of human serum albumin depending on pH. Study using tritium markers].
Accessible surfaces of the HSA molecule in N-, F- and B-forms were studied in the present work by tritium labelling method which allowed to obtain detailed information on N-F- and N-B-transitions. In was shown that the F-form in comparison top the N-form is characterized by more high accessibility of Ser, Ala, Ile, Tyr, Phe, His, Arg, Pro, Val and Phe residues and in the B-form Tyr, Ser, Arg, Gly, Ile, Phe and Pro residues turn to be highly accessible. Full accessible surfaces of protein molecule at N-F- and N-B-transitions increase respectively from 39,000 to 70,400 A2 and from 39,000 to 47,000 A2. Basing on the prevailing increase of hydrophobic residues accessibility it is supposed that the molecule expansion testifies the separation of the subunits forming the molecule.