Associations of kidney tests at medical facilities and health checkups with incidence of end-stage kidney disease: a retrospective cohort study.
No study has assessed the association between no health checkup and end-stage kidney disease (ESKD). This retrospective cohort study, including 69,147 adults aged ≥ 40 years in Japan who were insured by the National Health Insurance and the Late-Stage Medical Care System for the Elderly, assessed the associations of kidney tests at medical facilities and health checkups with incident ESKD. The main exposure was the histories of kidney tests using dipstick urinalysis and/or serum creatinine measurement at medical facilities and checkups in the past year: "checkups," "no kidney test (without checkup)," and "kidney tests (without checkup)" groups. During the median observational period of 5.0 years, ESKD was observed in 246 (0.8%) men and 124 (0.3%) women. The "no kidney test" group was associated with ESKD in men (adjusted subhazard ratio of "no kidney test" vs. "checkups": 1.66 [95% confidence interval, 1.04-2.65], but not in women. Age-specific subgroup analyses identified the "no kidney test" group as a high-risk population of ESKD in elderly men (1.30 [0.70-2.41] and 2.72 [1.39-5.33] in men aged 40-74 and ≥ 75 years, respectively). Elderly men with no kidney test at medical facilities and no health checkup were at higher risk of ESKD.


Morphologic analysis of the pulmonary vascular bed in congenital left-sided diaphragmatic hernia.
The contribution of an abnormal pulmonary vascular bed to right-to-left shunting in patients with congenital left-sided diaphragmatic hernia and alveolar hypoplasia has not been defined. In three infants we analyzed lungs fixed by perfusion. Left lung volumes (ml/kg birth weight) were 1.7, 6.5 and 4.0 respectively (control = 11.7) and right lung volumes 5.7, 11.7 and 9.8 respectively (control = 14.3). Serial sections were prepared and fifth generation (resistance) vessels identified. Compared to control the medial widths were increased in all lungs and the medial width/external diameter ratios were increased in the left lungs of two patients and the right lung of one. The m/d ratio in the left lung was greater than that in the right lung in two of the three patients. There were fewer pulmonary vessels/cm2 lung tissue in the study lungs than in the control lung, and there were significantly fewer pulmonary vessels/cm2 lung tissue in the left than in the right lung in two of the three patients. Although there was increased smooth muscle in resistance vessels, intravenous therapy with tolazoline HCl did not improve systemic oxygenation. We conclude that this was probably due to the decreased total size of the pulmonary vascular bed and the decreased number of pulmonary vessels per unit lung tissue, causing a fixed high pulmonary vascular resistance.


A randomized controlled trial to investigate the influence of low dose radiotherapy on immune stimulatory effects in liver metastases of colorectal cancer.
Insufficient migration and activation of tumor specific effector T cells in the tumor is one of the main reasons for inadequate host anti-tumor immune response. External radiation seems to induce inflammation and activate the immune response. This phase I/II clinical trial aims to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with colorectal liver metastases. This is an investigator-initiated, prospective randomised, 4-armed, controlled Phase I/II trial. Patients undergoing elective hepatic resection due to colorectal cancer liver metastasis will be enrolled in the study. Patients will receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation targeted to their liver metastasis. Radiation will be applied by external beam radiotherapy using a 6 MV linear accelerator (Linac) with intensity modulated radiotherapy (IMRT) technique two days prior to surgical resection. All patients admitted to the Department of General-, Visceral-, and Transplantion Surgery, University of Heidelberg for elective hepatic resection are consecutively screened for eligibility into this trial, and written informed consent is obtained before inclusion. The primary objective is to assess the effect of active local external beam radiation dose on, tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include radiogenic treatment toxicity, postoperative morbidity and mortality, local tumor control and recurrence patterns, survival and quality of life. Furthermore, frequencies of systemic tumor reactive T cells in blood and bone marrow will be correlated with clinical outcome. This is a randomized controlled patient blinded trial to assess the safety and efficiency of low dose radiotherapy on metastasis infiltrating T cells and thus potentially enhance the antitumor immune response. ClinicalTrials.gov: NCT01191632.


Real world MRI experience with nonconditional and conditional cardiac rhythm devices after MagnaSafe.
The recent MagnaSafe Registry demonstrated safety of nonthoracic magnetic resonance imaging (MRI) with nonconditional cardiac implantable electronic devices (CIEDs). However, independent validation and extension to thoracic MRIs are needed. We prospectively examined 178 consecutive patients with CIEDs who underwent 212 MRI scans (62 with implantable cardioverter/defibrillators) for clinical reasons between February 2014 and August 2016. Scans were done in standard modes with a limit of 2 W/kg. Pacing modes were ODO or OVO for intrinsic rates > 40 and DOO or VOO for rates ≤ 40. Patients were cleared prescan by both radiology and cardiology, and pre- and postscan CIED interrogations were performed. Primary outcome events were death and generator or lead failure. Secondary events included battery voltage loss > 0.04 V, decrease in P wave voltage > 50% or R wave voltage > 25%, threshold increase of > 0.5 V, and impedance change > 50 Ω. Scan sites were 87 (41%) C-spine/head/neck, 28 (13%) T-spine/cardiac/shoulder (thoracic), 69 (33%) L-spine/abdomen/pelvis, and 28 (13%) lower extremity. No primary or secondary outcome events occurred, and no periscan disruption of pacing was noted. In a real-world MRI experience in patients with CIEDs representing a broad range of models, types, and scan sites (including thoracic scans), no adverse safety signals were noted. This experience validates and extends that of the large but inclusion-restricted MagnaSafe Registry, profiles MRI scanning in CIED patients in general clinical practice, and argues against replacing nonconditional with conditional devices when MRI is performed in a carefully controlled environment.


Antipsychotic prescribing patterns and the treatment of extrapyramidal symptoms in older people.
We have previously identified antipsychotic use as a risk factor for the use of both dopaminergic and anticholinergic antiparkinsonian drugs in older people. This study examines whether and how such antipsychotic regimens were adjusted before the addition of an antiparkinsonian drug. Retrospective comparison study There were 1307 antipsychotic users begun on anticholinergic antiparkinsonian drugs and 345 antipsychotic users begun on dopaminergic drugs; 1864 antipsychotic users not prescribed antiparkinsonian drugs served as comparison subjects. Data were drawn from health care claims of patients aged 65-99 in the New Jersey Medicaid Program from 1981 to 1990. We determined if antipsychotic regimens were discontinued, reduced in dosage, or modified to reduce extrapyramidal toxicity before the institution of antiparkinsonian therapy. Thirty-five percent of the patients begun on dopaminergic drugs had their antipsychotic medication discontinued before beginning antiparkinsonian therapy; the antipsychotic was discontinued in only 12% of patients who started anticholinergic medications (P < .001). Among the smaller subset of patients with sufficient duration of antipsychotic exposure to examine changes in dose, 54% of patients begun on dopaminergic agents had their antipsychotic regimen reduced or discontinued before antiparkinsonian therapy, whereas 33% of patients begun on anticholinergic agents had one of these regimen changes (P < .001). Controlling for potential clinical and demographic confounders using multivariate logistic regression did not substantively alter these results. These data indicate that physicians frequently fail to discontinue or modify an antipsychotic regimen before adding a new drug to treat probable drug-induced extrapyramidal symptoms. Such prescribing patterns preceding use of dopaminergic antiparkinsonian drugs suggest that addition of such drugs may represent an inappropriate attempt to treat presumed idiopathic Parkinson's disease in many cases.


Biomechanical assessment of screw safety between far cortical locking and locked plating constructs.
With the emerging concerns for more flexible and less stiff bridge constructs in the interest of stimulating bone healing, the technique of far cortical locking has been designed to reduce the stiffness of locked plating (LP) constructs while retaining construct strength. This study utilized simulation with diaphyseal bridge plating biomechanical models to investigate whether far cortical locking causes larger screw fracture risk than LP during rehabilitation. The fracture risk of the screws in the far cortical locking constructs increases in the non-osteoporotic and osteoporotic diaphysis compared with the screws in the LP constructs.


[Resection of the trachea with extracorporeal circulation as a simultaneous procedure during coronary artery bypass grafting--a case report].
The authors describe their surgical management of a female patient with a symptomatic coronary artery disease, who had developed a postintubation stenosis of the trachea. The patient sufferred from a rest dyspnoea with stridor. The unusual combination of the both cardiac and tracheal disorders were managed employing a one-step cardio-thoracic surgical procedure. The tracheal resection was conducted in the extracorporeal circulation condition together with the myocardial revascularization. The case shows how, in indicated cases, availability of the extracorporeal circulation can widen a spectrum and limits of the standard chest surgery.


Home parenteral nutrition in adults: a multicentre survey in Europe.
This registry describes a multicentre experience of Home Parenteral Nutrition (HPN) in nine European countries covering 27 centres and 194 patients. The main purpose of this study was to evaluate the quality of life and prognosis of patients on HPN. Patients started HPN at 44 +/- 1 years old (mean +/- SEM), and received 200 courses of HPN for a mean of 12 +/- 1 months representing a cumulative duration of 207 years. The four commonest indications for HPN were inflammatory bowel disease (30%), mesenteric vascular disease (21%), malignancy (17%) and radiation enteritis (13%). The nutritional status during HPN was clinically normal or subnormal in 93% of cases. The yearly incidence of catheter related complications leading to a catheter change was 0.74, sepsis accounting for half of this. The duration of hospital readmission for HPN complications was 4 +/- 1% of time spent at home, which represents 2 weeks per year and 41% of the total readmission time. Mortality was mainly influenced by the underlying disease since only 3% of patients died of HPN complications. A good social rehabilitation was observed in 52% of patients who during treatment recovered their pre-HPN occupational status. The poorest social rehabilitation was observed in patients over 65 years of age, and patients with malignancies and radiation enteritis, who also had the poorest prognosis. Caution seems necessary before recommending HPN in these patients.


[Place of radiotherapy in the treatment of rectal cancer in the elderly].
Rectal cancer is a common disease of the elderly. Current treatment recommendations are established for young subjects in good general health condition, without taking into account the frailty, comorbidities and polymedications inherent in patients over 75 years old. For locally advanced lower and middle rectal cancers (T3, T4 or N+), these are based on variations of regimens including neoadjuvant chemoradiotherapy, surgery of the rectum with total removal of the mesorectum, and a possibility of adjuvant chemotherapy. This restrictive treatment presents a problem of compliance and is not without adverse effects. Treatment by short exclusive radiotherapy or chemoradiotherapy with close monitoring according to the Watch and Wait strategy can be proposed to fragile patients not eligible for surgery, even if there is a non-negligible risk of recurrence.


Incidence, prevalence, and occurrence rate of infection among adults hospitalized after traumatic brain injury: study protocol for a systematic review and meta-analysis.
Infection occurs commonly among patients hospitalized after traumatic brain injury (TBI) and has been associated with increased intensive care unit and hospital lengths of stay and an elevated risk of poor neurological outcome and mortality. However, as many relevant published studies to date have varied in the type and severity of TBI among included patients as well as in their design (randomized versus non-randomized), risk of bias, and setting (hospital ward versus intensive care unit), their reported estimates of infection occurrence vary considerably. Thus, the purpose of this systematic review and meta-analysis is to estimate the incidence, prevalence, and occurrence rate of infection among patients hospitalized after TBI. We will search electronic bibliographic databases (MEDLINE, EMBASE, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews) from their first available date as well as personal files, reference lists of included articles, and conference proceedings. Two investigators will independently screen titles and abstracts and select cohort studies, cross-sectional studies, and randomized controlled trials involving adults hospitalized after TBI that reported estimates of cumulative incidence, incidence rate, prevalence, or occurrence rate of infection for inclusion in the systematic review. These investigators will also independently extract data and assess risk of bias. We will exclude studies with fewer than ten patients; experimental groups allocated to treatment with antibiotics, glucocorticoids, immunosuppressants, barbiturates, or hypothermia; and studies focused on military/combat-related TBI. Pooled estimates of cumulative incidence, incidence rate, prevalence, and occurrence rate will be calculated using random effects models. We will also calculate I2 and Cochran Q statistics to assess for inter-study heterogeneity and conduct stratified analyses and univariate meta-regression to determine the influence of pre-defined study-level covariates on our pooled estimates. This study will compile the world literature regarding the epidemiology of infection among adults hospitalized after TBI. A better understanding of the role of infection will be helpful in the development of guidelines for patient management. This protocol has been registered in the PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42013005146).


14-3-3 binding and phosphorylation of neuroglobin during hypoxia modulate six-to-five heme pocket coordination and rate of nitrite reduction to nitric oxide.
Neuroglobin protects neurons from hypoxia in vitro and in vivo; however, the underlying mechanisms for this effect remain poorly understood. Most of the neuroglobin is present in a hexacoordinate state with proximal and distal histidines in the heme pocket directly bound to the heme iron. At equilibrium, the concentration of the five-coordinate neuroglobin remains very low (0.1-5%). Recent studies have shown that post-translational redox regulation of neuroglobin surface thiol disulfide formation increases the open probability of the heme pocket and allows nitrite binding and reaction to form NO. We hypothesized that the equilibrium between the six- and five-coordinate states and secondary reactions with nitrite to form NO could be regulated by other hypoxia-dependent post-translational modification(s). Protein sequence models identified candidate sites for both 14-3-3 binding and phosphorylation. In both in vitro experiments and human SH-SY5Y neuronal cells exposed to hypoxia and glucose deprivation, we observed that 1) neuroglobin phosphorylation and protein-protein interactions with 14-3-3 increase during hypoxic and metabolic stress; 2) neuroglobin binding to 14-3-3 stabilizes and increases the half-life of phosphorylation; and 3) phosphorylation increases the open probability of the heme pocket, which increases ligand binding (CO and nitrite) and accelerates the rate of anaerobic nitrite reduction to form NO. These data reveal a series of hypoxia-dependent post-translational modifications to neuroglobin that regulate the six-to-five heme pocket equilibrium and heme access to ligands. Hypoxia-regulated reactions of nitrite and neuroglobin may contribute to the cellular adaptation to hypoxia.


Inhibiting effect of dry heat on the heat-induced aggregation of egg white protein.
This study investigated the effect of dry heat on the aggregation characteristics of egg white protein (EWP) solutions. Turbidity and size-exclusion chromatography (SEC) results showed that dry heat hindered the subsequent bulk aggregation of dry heated EWP (DEWP) in aqueous solutions. A similar trend was also found in the particle size distribution of DEWP aggregates, where longer dry heating times resulted in smaller size distributions. Transmission electron microscopy (TEM) observations showed that native EWP tended to form bulk aggregates when heated in aqueous solutions, while DEWP aggregates presented linear and chain-like morphology. The α-helices of DEWP aggregates were converted to β-sheets, and more chromogenic amino acids and hydrophobic groups were exposed owing to dry heat. Heat-induced aggregation of DEWP in water is more intense than that induced only by dry heat, but the hydrothermal aggregates with longer dry heating times were smaller in size and molecular weight.


The prevalence of antibiotic resistance in bacterial respiratory pathogens from Norway is low.
To determine the degree of bacterial susceptibility to the most commonly used drugs for respiratory infections in Norway, and to find if bacterial resistance is emerging. Clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and group A streptococci from respiratory tract specimens and from the eye were collected from different parts of Norway during two study periods. During the first period (1993-1994), three laboratories, covering 15% of the Norwegian population, participated. During the second study period in 1997, five laboratories, covering 27% of the population, collected respiratory isolates. In total, 494 isolates of S. pneumoniae, 696 isolates of H. influenzae and 694 isolates of group A streptococci were included in the study. The study population comprised children and adults attending hospital and general practice. Bacterial susceptibility was determined by the E test, and breakpoints were according to the National Committee for Clinical Laboratory Standards (NCCLS). The prevalence of bacterial resistance was low, and we observed no significant increase in bacterial resistance between the two study periods. In 1997, only 0.6% of pneumococci had decreased susceptibility to penicillin, 1.6% of group A streptococci were resistant to erythromycin, and 6.7% of all isolates of H. influenzae produced beta-lactamase. The prevalence of antibiotic resistance in respiratory pathogens in Norway is low.


Neonatal Screening for Prevalence of Hearing Impairment in Rural Areas.
Hearing is one of the most important sense organs for man. Hearing loss is often associated with delayed speech and language development in young children. Early identification and intervention improves the chance a child gets to lesser delays in development and improving the overall quality of life. To find out the prevalence of hearing loss in neonates in the rural taluka of Maval, Pune, Maharashtra, India. Prospective Non Randomized Clinical Study. The study was carried out between April 2012 and April 2015. A total of 8192 babies were screened across various centers around the Maval area. The babies who had some high risk factors were 1683 in number and babies who had no high risk factors i.e. well babies were 6509. In our study, the overall prevalence of hearing loss in neonates in Maval taluka of Maharashtra was found to be 3.54 per 1000 live births, in normal born neonates (well babies) was 1.689 per 1000 births, in high risk babies was 10.69 per 1000 high risk births. The prevalence of low birth weight neonates, hyperbilirubinemia neonates and neonates with craniofacial abnormalities developing hearing impairment was found to be 5.9, 3.56 and 1.18 per 1000 high risk births respectively. India is the second most populated country in the world with nearly a fifth of the world's population. There is a need for the universal neonatal screening for deafness for earlier detection of deafness and rehabilitation. Level of Evidence: Level IV.


Uncommon Site of Metastasis and Prolonged Survival in Patients with Anaplastic Thyroid Carcinoma: A Systematic Review of the Literature.
Anaplastic thyroid carcinoma (ATC) is a very rare, highly aggressive malignant thyroid tumor with an overall survival from 3 to 5 months in most of the cases. Even the modern and intensive treatments seem not to be enough to provide a cure, also for the resectable ones, and the role of chemotherapy is still unclear but does not seem to prolong survival. Nevertheless, some patients survive longer and have a better outcome, even in the presence of metastasis, than what the literature reports. We present the case of a 64-year-old female affected by ATC, treated on February 2018 with surgery followed by chemoradiation. One year after surgery, the patient developed a subcutaneous recurrence that was radically resected and is still alive 29 months after the diagnosis. We propose a systematic review of the literature to deepen the knowledge of the prognostic factors of ATC with the aim to recognize and select the patients with a better outcome, even if metastatic, and to describe a very uncommon site of metastatization.


Diastereomeric difference of inclusion modes between (-)-epicatechin gallate, (-)-epigallocatechin gallate and (+)-gallocatechin gallate, with beta-cyclodextrin in aqueous solvent.
Inclusion complexes of (-)-epicatechin gallate (ECg) as well as (+)-gallocatechin gallate (GCg) and beta-cyclodextrin (beta-CD) in an aqueous solution were investigated using several NMR techniques and a computational method. ECg and EGCg formed a 1:1 complex with beta-CD, in which the A ring and a portion of the C ring were included from the wide secondary hydroxyl group side of the beta-CD cavity, and the B and B' rings were left outside the cavity. GCg formed a 1:2 complex with beta-CD, in which the A and B rings of GCg were included by two molecules of beta-CD. The difference between the two modes of inclusion of the 1:1 complex of ECg, EGCg.beta-CD and the 1:2 complex of GCg.beta-CD might have resulted from the size of the space between the B and B' rings in aqueous solution. As a result of nuclear Overhauser effect (NOE) experiments, GCg was considered to have a large enough space between the B and B' rings to include the B ring in the beta-CD cavity; on the other hand, ECg and EGCg have no such large space.


Acetylcholine content of and release from isolated pelviureteral tract.
Measurements were taken for the acetylcholine content of animal and human pelviureteral muscle and for the release of acetylcholine at rest and during field stimulation of the isolated renal pelvis and ureter. Release was frequency-dependent, with the maximum output obtained at 10 Hz. The release of acetylcholine from reserpine-pretreated and piperoxan-treated tissues remained unchanged, but tetrodotoxin (1.10(-6) g/ml) and noradrenaline (2.10(-6) g/ml) significantly reduced the output.


Familial florid osseous dysplasia: a case report.
Most cases of florid osseous dysplasia are asymptomatic and are found during routine radiographic examination. The radiographic spectrum is similar to that of other benign fibro-osseous lesions, beginning as a radiolucent lesion and becoming more radiopaque as the involved bone becomes more sclerotic. Many benign fibro-osseous lesions demonstrate similar histologic features, and without other radiographic and clinical information, a definitive diagnosis may be impossible. The dense bone of florid osseous dysplasia is very susceptible to infection and osteomyelitis, particularly with advancing years and in response to trauma. The disease may be self-limiting as reported by many authors, but as in this case, can be symptomatic for most of the person's lifetime. This presents a diagnostic and treatment dilemma for the clinician. Although this entity has a distinct predilection for black women, more reported cases should be evaluated before the mode of inheritance can be established and before a tendency for familial cases in individuals of Italian descent can be confirmed.


Percoll purification of chromaffin granules inhibits their ability to take up and maintain calcium.
Secretory granules of the adrenal medulla have recently been shown to be able to sequester and release Ca2+, in addition to their previously established role as carriers of secretory products. In order to study the ability of these or any other secretory granules to participate in intracellular calcium homeostasis, it is imperative that they should be free of other contaminating Ca2+ sequestering organelles, and that the Ca2+ uptake and release mechanisms of those granules should remain intact throughout any chosen purification procedure. We report here that chromaffin granules which were purified by the isopycnic gradient medium Percoll, or even incubated with it, showed an attenuated ability to sequester Ca2+.


Unexplained infertility: A French national survey of clinical practices.
The aim of our study was to carry out a national survey of French practitioners to evaluate (i) their diagnostic criteria for making a diagnosis of unexplained infertility (UEI) and (ii) their management strategy when facing UEI. An online questionnaire comprising ten multiple-choice questions was sent by mail to French reproductive practitioners in 80 fertility centres. The response rate was 59.6% (195/327). Post coital testing was always or often prescribed by 14.8% of respondents (n = 36). Chlamydia trachomatis testing was never prescribed by 31.7% (n = 59) of them, 30.2% prescribed a pelvic MRI in cases of UEI and 18.4% (n = 33) always or often performed laparoscopy. For 87.6% (n = 169), advanced maternal age was always or often an indication of first-line IVF, with an average threshold of 37.4 years. For 68.6% (n = 129), diminished AMH was an indication for first-line IVF, with an average AMH threshold of 1.2 ng/ml. With respect to the management of UEI, we did not observe a consensus between the strategies of 2 to 6 intrauterine insemination cycles before IVF or IVF as the first-line treatment. There is no consensus in France on what tests should or should not be carried out to conclude UEI, and there is also no consensus on the management of UEI. UEI is one of the top 10 priorities for future infertility research. The diagnostic criteria must be standardized to enable the comparison of studies on this topic as well as to improve the translation of research into clinical practice.


Exploration on the effect of predeposit autotransfusion on bone marrow hematopoiesis after femoral shaft fracture.
By observing the changes in the number and activity of CD34+ cells in bone marrow after predeposit autotransfusion (PAT) to patients with femoral shaft fracture (FSF), to evaluate the effects of PAT on hematopoietic function and hematopoietic stem cells in bone marrow. Selected FSF patients were randomly divided into 2 groups: the control group (patients did not receive blood transfusion after surgery) and PAT group (patients received PAT after surgery). The content of RBC and Plt in blood samples were counted by blood routine. The cell cycle and proportion of CD34+ myelinated cells in blood samples was analyzed by flow cytometry. The telomere DNA length of hematopoietic stem cells (HSCs) in the control groups and PAT group at postoperation 24 was analyzed by southern blot. The content of RBC and Plt in postoperation 6h and 24h in the control group was evidently higher compared to that in PAT group, while Hb content in control group was significantly lower compared to that in PAT group. The proportion of CD34+ myelinated cells in post-transfusion 6h and postoperation 24h in PAT group was evidently higher compared to that in the control group. In PAT group, S phase at postoperation 24h was significantly larger compared to that at post-transfusion 6h. The telomere DNA length of HSCs in PAT group was longer than that in the control group. PAT can increase the number of HSC, while does not cause the abnormal aging of HSCs. PAT is suitable for postoperative blood transfusion of patients with FSF.


1-(3,5-Di-nitro-benzo-yl)-4-(2-meth-oxy-phen-yl)piper-azine.
In the title compound, C18H18N4O6, the piperazine ring adopts a chair conformation, the amidic N atom is planar (sum of angles = 360°) and the non-amidic N atom is pyramidal (343°). There are no hydrogen bonds of any kind in the crystal, but the mol-ecules are linked by two independent π(nitro-benzene)⋯π(meth-oxy-benzene) stacking inter-actions to form π-stacked sheets with inter-centroid separations of 3.8444 (12) and 3.9197 (12) Å.


CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increases endoxifen serum concentrations without increasing side effects.
Breast cancer patients with absent or reduced CYP2D6 activity and consequently low endoxifen levels may benefit less from tamoxifen treatment. CYP2D6 poor and intermediate metabolizers may need a personalized increased tamoxifen dose to achieve effective endoxifen serum concentrations, without increasing toxicity. From a prospective study population of early breast cancer patients using tamoxifen (CYPTAM: NTR1509), 12 CYP2D6 poor and 12 intermediate metabolizers were selected and included in a one-step tamoxifen dose escalation study during 2 months. The escalated dose was calculated by multiplying the individual's endoxifen level at baseline relative to the average endoxifen concentration observed in CYP2D6 extensive metabolizers by 20 mg (120 mg maximum). Endoxifen levels and tamoxifen toxicity were determined at baseline and after 2 months, just before patients returned to the standard dose of 20 mg. Tamoxifen dose escalation in CYP2D6 poor and intermediate metabolizers significantly increased endoxifen concentrations (p < 0.001; p = 0.002, respectively) without increasing side effects. In intermediate metabolizers, dose escalation increased endoxifen to levels comparable with those observed in extensive metabolizers. In poor metabolizers, the mean endoxifen level increased from 24 to 81 % of the mean concentration in extensive metabolizers. In all patients, the endoxifen threshold of 5.97 ng/ml (=16.0 nM) reported by Madlensky et al. was reached following dose escalation. CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increased endoxifen concentrations without increasing short-term side effects. Whether such tamoxifen dose escalation is effective and safe in view of long-term toxic effects is uncertain and needs to be explored.


Establishing a contract for a PACS managed service.
This review considers the process of contracting for a picture archiving and communication system (PACS) using the private finance initiative (PFI) managed service route. The PFI process is reviewed and the advantages and disadvantages of a managed service detailed. During contract negotiations several areas of conflict were encountered. These are discussed with an outline of how they were resolved. A contract for a PACS has been achieved by a large acute hospital Trust using a managed service provision through PFI. In detailing the specific problems encountered in the course of negotiations, it is intended that other Trusts entering on this course will be equipped and strengthened in the finalizing of satisfactory and robust contracts.


Proteoforms and their expanding role in laboratory medicine.
The term "proteoforms" describes the range of different structures of a protein product of a single gene, including variations in amino acid sequence and post-translational modifications. This diversity in protein structure contributes to the biological complexity observed in living organisms. As the concentration of a particular proteoform may increase or decrease in abnormal physiological states, proteoforms have long been used in medicine as biomarkers of health and disease. Notably, the analytical approaches used to analyze proteoforms have evolved considerably over the years. While ligand binding methods continue to play a large role in proteoform measurement in the clinical laboratory, unanticipated or unknown post-translational modifications and sequence variants can upend even extensively tested and vetted assays that have successfully made it through the medical regulatory process. As an alternate approach, mass spectrometry-with its high molecular selectivity-has become an essential tool in detection, characterization, and quantification of proteoforms in biological fluids and tissues. This review explores the analytical techniques used for proteoform detection and quantification, with an emphasis on mass spectrometry and its various applications in clinical research and patient care including, revealing new biomarker targets, helping improve the design of contemporary ligand binding in vitro diagnostics, and as mass spectrometric laboratory developed tests used in routine patient care.


A novel mannose containing phenolic glycolipid from Mycobacterium kansasii.
Using high-performance liquid chromatography, a new kind of phenolic glycolipid quantitatively minor, called phenolic glycolipid-II, was isolated from a lipidic fraction of Mycobacterium kansasii. The structure was determined by fast atom bombardment-mass spectrometry and proton nuclear magnetic resonance spectroscopy, as: 2,4-di-O-Me-alpha-D-Manp(1----3) 4-O-Ac-2-O-Me-alpha-L-Fucp(1----3)2-O-Me- alpha-L-Rhap(1----3) 2,4-di-O-Me-alpha-L-Rhap 1----phenolphthiocerol dimycocerosate. Phenolic glycolipids I and II differ only by their distal monosaccharide hapten which is 2,6-dideoxy-4-O-Me-alpha-D-arabinohexopyranosyl and the 2,4-di-O-Me-alpha-D-mannopyranosyl, respectively. This sugar appears to be characteristic and apparently unique in the Mycobacterium genus. Moreover, phenolic glycolipids I and II constitute with the lipooligosaccharides two classes of antigens of M. kansasii.


Fibrate therapy and circulating adiponectin concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials.
Several lines of evidence have indicated the insulin-sensitizing, anti-diabetic and anti-atherosclerotic properties of adiponectin, as well as the inverse association between circulating levels of this adipokine and development of cardiovascular outcomes. Improvement of adiponectin status has been reported as a pleiotropic effect of fibrate therapy, but the findings have not been conclusive. To systematically review and meta-analyze available evidence from randomized placebo-controlled trials (RCTs) on the impact of fibrate therapy on circulating levels of adiponectin. A comprehensive literature search in Medline was carried out to identify RCTs comparing the effect of fibrate therapy vs. placebo on circulating concentrations of adiponectin. A meta-analysis of eligible studies was performed using a random-effects model. Quality assessment, sensitivity analysis and publication bias evaluations were conducted using standard methods. Twelve RCTs comprising 443 cases and 437 controls met the selection criteria for systematic review, out of which 9 RCTs (399 cases and 401 controls) were included in the meta-analysis. Quantitative data synthesis revealed a significant effect for fibrate therapy in increasing circulating adiponectin levels (weighed mean difference: 0.38 μg/mL; 95% confidence interval: 0.13-0.63 μg/mL; p = 0.003). The effect size remained statistically significant when restricting the analysis to fenofibrate trials [0.31 (0.21-0.42) μg/mL; p < 0.00001). The observed effect was robust in sensitivity analyses and independent of fibrate dose. Imputation for potential missing studies led to the estimation of a greater effect size for fibrate therapy [0.53 (0.24-0.82) μg/mL]. The present meta-analysis suggests that fibrate therapy increases circulating levels of adiponectin. Whether increase in adiponectin levels contributes to reduction of cardiovascular effects in subjects with dyslipidemia treated with fibrates merits further investigation.


Highly effective SNP-based association mapping and management of recessive defects in livestock.
The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal welfare concerns. Here we show that the availability of genome-wide, high-density SNP panels, combined with the typical structure of livestock populations, markedly accelerates the positional identification of genes and mutations that cause inherited defects. We report the fine-scale mapping of five recessive disorders in cattle and the molecular basis for three of these: congenital muscular dystony (CMD) types 1 and 2 in Belgian Blue cattle and ichthyosis fetalis in Italian Chianina cattle. Identification of these causative mutations has an immediate translation into breeding practice, allowing marker assisted selection against the defects through avoidance of at-risk matings.


Scannographic Study of Risk Factors of Abdominal Aortic Aneurysm Rupture.
Current decision about when to operate abdominal aortic aneurysms (AAAs) is based only on the maximum aneurysm diameter (MAD). However, small aneurysms still rupture and we can observe very large AAA without any symptom. A simple morphologic analysis could be a tool to assess the risk of rupture. The main objective of this study was to assess the relevance of ratios between MAD and healthy aorta on computed tomography (CT) as a risk factor of AAA rupture. The secondary objective was to evaluate CT signs as risk factors of AAA rupture. Retrospective observational bicentric study comparing CT scans of a ruptured AAA group and a control group treated electively was conducted. Appariement 1:1 based on MAD was applied. Ratios between healthy aorta diameters at several levels, celiac trunk (CTR), superior mesenteric artery (SMA), highest renal artery (RA), and the MAD were calculated. The presence of blebs, crescent signs, ruptures of calcifications of the aneurysm sack, and draped aorta were notified. From 2010 to 2016, 38 ruptured AAA and 38 controls were included. Ratios were superior in the rupture group, respectively: MAD/CTR [2.77 (±0.5) versus 2.58 (±0.4) P < 0.095], MAD/SMA [2.92 (±0.7) versus 2.74 (±0.5) P < 0.194], and MAD/RA [3.02 (±0.70) versus 2.76 (±0.5) P < 0.054] but not significatively. Receiver operating characteristic curve analysis demonstrated optimal threshold to detect rupture at 2.8 for the ratio MAD/CTR (area under the curve (AUC) 0.593, sensitivity 47.4%, specificity 78.9%), at 3.3 for the ratio MAD/SMA (AUC 0.564, sensitivity 31.6%, specificity 92.1%), and at 3.3 for the ratio MAD/RA (AUC 0.591, sensitivity 31.6%, specificity 94.7%). Bivariate analysis for rupture risk factor showed significance for the three ratios (MAD/CTR > 2.8 [OR = 11 (1.42; 85.20) P < 0.0217], MAD/SMA > 3.3 [OR = 10 (1.28; 78.12) P < 0.0281], and MAD/RA >3.3 [OR = 11.00 (1.42; 85.20) P < 0.0217]). One scannographic sign was more present in the rupture group: crescent sign 36.8% versus 5.3%, P = 0.0007, as well in bivariate analysis [OR = 7 (1.59; 30.80) P < 0.0326]. In our experience, specific ratios when they exceed calculated threshold, seem to be more prone to rupture. We could consider that these measures, easy to apply in clinical practice, would be complementary keys for rupture risk individual assessment.


Determination of anthraquinones in Rhamnus purshiana using high-performance liquid chromatography coupled to diode array detector and simple ultraviolet spectroscopic analysis.
A new method based on Ultraviolet spectrophotometry was developed and compared with that based on high-performance liquid chromatography for the determination and quantification of anthraquinones in the extracts of Rhamnus purshiana bark. A validated quantitative analysis of cascaroside A, cascaroside B, emodin, and aloe-emodin in these herbal products has been previously performed using high-performance liquid chromatography coupled with a diode array detector. In the high-performance liquid chromatography analysis, all the anthraquinones showed satisfactory regression (r2 > 0.98) within the test ranges, and the recovery was in the range of 94-117%. The limits of detection and quantification were 0.008-0.010 and 0.029-0.035 μg/mL, respectively. Hierarchical cluster analysis and principal component analysis showed differences in the anthraquinones determined from herbal samples. Subsequently, a simple and low-cost ultraviolet spectrophotometric methodology for the quantitative analysis of the same compounds in the extracts was applied, and all the contents were determined. A paired t-test confirmed that there were no significant differences between the two methods. Our results revealed that the developed method is simple and provides the ability to discriminate and control the quality of anthraquinones in herbal products.


The structure activity relationship of discodermolide analogues.
The marine polyketide discodermolide is a member of a class of natural products that stabilize microtubules. Many analogues have been synthesized suggesting that few changes can be made to the internal carbon backbone. Both ends of the molecule, however, can be modified. The majority of analogues have been generated via modification of the lactone region. This suggests that significant simplifications can be made in this region provided that the lactone moiety is maintained.


ATM increases activation-induced cytidine deaminase activity at downstream S regions during class-switch recombination.
Activation-induced cytidine deaminase (AID) initiates Ab class-switch recombination (CSR) in activated B cells resulting in exchanging the IgH C region and improved Ab effector function. During CSR, AID instigates DNA double-strand break (DSB) formation in switch (S) regions located upstream of C region genes. DSBs are necessary for CSR, but improper regulation of DSBs can lead to chromosomal translocations that can result in B cell lymphoma. The protein kinase ataxia telangiectasia mutated (ATM) is an important proximal regulator of the DNA damage response (DDR), and translocations involving S regions are increased in its absence. ATM phosphorylates H2AX, which recruits other DNA damage response (DDR) proteins, including mediator of DNA damage checkpoint 1 (Mdc1) and p53 binding protein 1 (53BP1), to sites of DNA damage. As these DDR proteins all function to promote repair and recombination of DSBs during CSR, we examined whether mouse splenic B cells deficient in these proteins would show alterations in S region DSBs when undergoing CSR. We find that in atm(-/-) cells Sμ DSBs are increased, whereas DSBs in downstream Sγ regions are decreased. We also find that mutations in the unrearranged Sγ3 segment are reduced in atm(-/-) cells. Our data suggest that ATM increases AID targeting and activity at downstream acceptor S regions during CSR and that in atm(-/-) cells Sμ DSBs accumulate as they lack a recombination partner.


A virtual simulation-based educational application about complementary and alternative medicine: A pilot study of nurses' attitudes and communication competency.
Conventional healthcare professionals have insufficient knowledge about complementary/alternative medicine (CAM) and often lack competencies to overcome attitudinal barriers to communicate effectively with patients about CAM. Interacting with a virtual simulation-based educational application program may help nurses learn current evidence and acquire communication skills when consulting with patients. The aim of this pilot study was to evaluate nurses' attitudes towards patients' CAM use and their competency in communicating with patients about CAM after interacting with a virtual simulation-based educational app. A quasi-experimental study with one-group, pretest-posttest design. A total of 49 nurses volunteered to participate in the study. Participants interacted with a virtual simulation software app on a smartphone that included audiovisual presentations about CAM, 13 exercises, and a risk-benefit decision assessment. Data about nurses' attitudes and communication competency were collected at baseline and after completing the 13 exercises. Descriptive and comparative statistics were analyzed using the IBM® SPSS® version 22.0. Both the nurses' attitudes about patients' CAM use and communication competency improved significantly following the completion of the 13 exercises. The risk-benefit decision scores correlated significantly with the increase in nurses' attitudes and their communication competency. Using a virtual simulation-based educational app may help nurses not only increase their attitudes towards CAM but also increase their communication competency in consulting with patients about CAM use.


Who plans to be tested for HIV or would get tested if no one could find out the results?
We analyzed the characteristics of individuals at risk for HIV who have not been tested but who (1) planned to be tested, or (2) would get tested "if no one other than you (the respondent) could find out your results." Data were from the 1991 National AIDS Behavioral Surveys, a probability sample of the U.S. population. Logistic regression was used to analyze the correlates of testing behavior among the 41% of individuals in high-prevalence cities who had HIV risk factors (n = 3,175). Of this group, 7% planned to be tested and 30% would get tested "if no one other than you could find out the results." Minorities and individuals with less education and without insurance were more likely to plan to be tested (versus previously tested), and individuals with less education and lower incomes were more likely to be willing to be tested "if no one other than you could find out the results" (versus previously tested). We conclude that a variety of options to increase testing rates should be explored, including accessible testing services, policies and procedures to increase perceptions of testing privacy, and home testing.


Modulation of angiogenic processes in cultured endothelial cells by low density lipoproteins subfractions from patients with familial hypercholesterolemia.
Electronegative low density lipoprotein (LDL) subfractions are cytotoxic to endothelial cells. To continue our study of homozygotic familial hypercholesterolemic (FH)-LDL, we report the effects of FH-LDL subfractions (FH-L1 to FH-L5) on the angiogenic processes in cultured endothelial cells. Subconfluent bovine aortic endothelial cells (BAEC) were treated with LDL subfractions (20 microg/ml), and the effects on angiogenic functions, including cell proliferation, migration, apoptosis, tube formation, secretion of matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF) were determined. The electronegative FH-L4 and FH-L5 inhibited cell proliferation while the other FH-LDL subfractions and LDL from normocholesterolemic subjects (N-LDL) had negligible effects. Like Cu2+ ox-LDL, FH-L5 strongly inhibited endothelial cell viability and FH-L4 had a milder effects. Similarly, FH-L4 and FH-L5 but not the other subfractions retarded cell migration, induced cell apoptosis, and perturbed tube formation by BAEC in matrigel. FH-L5 inhibited secretion of MMP-2 and MMP-9 by BAEC without affecting their endogenous levels. In contrast, FH-L5 increased the VEGF expression in endothelial cells. Our results show for the first time that FH-L5, a circulating LDL subfraction from hypercholesterolemic patients, modulates various angiogenic processes, thereby dysregulating endothelial function in a way that may be atherogenic.


Cross-correlation between EMG and center of gravity during quiet stance: theory and simulations.
Several signal processing tools have been employed in the experimental study of the postural control system in humans. Among them, the cross-correlation function has been used to analyze the time relationship between signals such as the electromyogram and the horizontal projection of the center of gravity. The common finding is that the electromyogram precedes the biomechanical signal, a result that has been interpreted in different ways, for example, the existence of feedforward control or the preponderance of a velocity feedback. It is shown here, analytically and by simulation, that the cross-correlation function is dependent in a complicated way on system parameters and on noise spectra. Results similar to those found experimentally, e.g., electromyogram preceding the biomechanical signal may be obtained in a postural control model without any feedforward control and without any velocity feedback. Therefore, correct interpretations of experimentally obtained cross-correlation functions may require additional information about the system. The results extend to other biomedical applications where two signals from a closed loop system are cross-correlated.


[Melanoma, from diagnosis to treatment].
Skin cancers represent a major public health problem. Cutaneous melanoma, the incidence of which is constantly increasing, has the particularity of metastasising when it is detected too late. Its treatment at the metastatic stage has evolved significantly over recent years with the arrival of targeted therapies and immunotherapies which can increase patients' survival.


Electronic and steric effects in gold(i) phosphine thiolate complexes.
The unusual yellow color of Au(2)(dppm)(SR)(2) (R = 4-tolyl; dppm = diphenylphosphinomethane) is attributed to a red-shift in the S-->Au charge transfer caused by destabilization of the sulfur highest occupied molecular orbital (HOMO). Variable temperature experiments show two broad bands at -80 degrees C in the (31)P{(1)H} NMR spectrum of Au(2)(dppm)(SR)(2) and the activation energy for interconversion is 10 kcal/mol. Only one sharp band is observed down to -80 degrees C in the spectrum of the white complex, Au(2)(dppe)(SR)(2) (dppe = diphenylphosphinoethane). Molecular mechanics calculations on Au(2)(dppm)(SR)(2) and Au(2)(dppe)(SR)(2) reveal that, for Au(2)(dppe)(SR)(2), a series of maxima and minima, separated by 2.5 kcal/mol, occur every 120 degrees which is consistent with rotation around an unhindered carbon-phosphorus single bond. The Au atoms are not within bonding distance in any conformation. Computational results for Au(2)(dppm)(SR)(2) indicate one minimum energy structure in which the Au-P bonds are anti. There is a high energy conformation (9 kcal/mol above the global minimum) where overlap between golds is maximized. The implications of gold-gold bonding in this complex are discussed. The steric influence of the thiolate ligand has been examined by synthesizing a series of dinuclear gold(I) complexes in which the steric properties of the thiolate are varied: Au(2)(dppm)(SR)(2) (R = 2,6-dichlorophenyl; 2,6-dimethylphenyl; 3,5-dimethylphenyl). The 2,6-disubstituted complexes are white, while the 3,5-dimethyl complex is yellow. These results, along with VT-NMR experiments, are consistent with the conclusion that the more sterically-bulky thiolates hinder the close approach of the golds in the dinuclear complexes.


Genetically destined potentials for N-linked glycosylation of influenza virus hemagglutinin.
The addition of oligosaccharide side chains to influenza virus hemagglutinin (HA) is believed to facilitate viral escape from immune pressure in the human population. To determine the implicit potentials for acquisition of N-linked glycosylation, we analyzed the genetic background of 16 subtypes of avian influenza virus, some of which may be potential pandemic viruses in the future. We found a significant difference among HA subtypes in their genomic sequences to produce N-glycosylation sites. Notably, recently circulating avian influenza viruses of the H5 and H9 subtypes may have rather greater capacities to undergo mutations associated with glycosylation of HA than past pandemic viruses. We hypothesize that influenza viruses maintained in natural reservoirs could have different potentials for sustained circulation, depending on their HA subtypes, if introduced into the human population.


Cytokine expression in peripheral blood lymphocytes indicates a switch to T(HELPER) cells in patients with preeclampsia.
We sought to determine whether cytokine expression in peripheral blood mononuclear cells is altered in patients with preeclampsia and in patients with a history of recurrent spontaneous abortion (RSA). Twenty-four patients with preeclampsia and twenty patients with a history of RSA were included into the study. Two control groups consisted of twenty healthy pregnant and twenty healthy non-pregnant women. The intracellular expression of interleukin-2 (IL-2), interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) were determined in peripheral blood mononuclear cells (PBMCs) by flow cytometry as a measure of cytokine production. IL-2 synthesis was significantly elevated in the third trimester in preeclamptic patients in comparison with the control group. Non-pregnant women with RSA showed a significantly lower expression of IFN-gamma compared to the non-pregnant control group. Our data suggest an abnormal immune response in preeclamptic patients characterised by a shift to a predominantly Th1-type immunity.


Variability in hospital costs for short stay emergent laparoscopic appendectomy.
Acute care surgery (ACS) diagnoses including appendicitis comprise 20% of inpatient admissions in the U.S. and 25% of hospital costs. To inform cost reduction efforts, we sought to measure variability in hospital costs for short stay emergent laparoscopic appendectomy. VIZIENT Clinical Data Base was queried for adult and pediatric patients who underwent emergent laparoscopic appendectomy for appendicitis with length of stay ≤3 days. We extracted calendar FY 2019 direct costs (DC) by age group and diagnosis code for sites reporting at least 5 cases. Costs in the database are derived from actual charges multiplied by a site- and cost center-specific cost-to-charge ratio. Labor portions are scaled by the area wage index. Sites were ranked by vigintile of DC per case to provide confidentiality and blinding. In a total of 128 hospitals, median number of cases per site was 35.5 (Interquartile range (IQR) 20-65) with a total of 6585 cases analyzed. Highest cost centers by descending order were OR, Medical/Surgical Supplies, Routine Floor Care, Pharmacy, Emergency Room, Anesthesia, Laboratory, and CT scans, with all others each less than 2% of total costs. The relation between OR costs and total costs was strong but not complete. Mean DC per case was $4609. DC did not correlate with age, diagnosis code, or case volume per site. Wide variation in cost of laparoscopic appendectomy among medical centers suggests potential for significant cost reduction. Strategic opportunities in cost reduction appear to lie inside and outside the OR. Wide variation in cost of laparoscopic appendectomy and individual cost centers suggest a multi-pronged cost-reduction strategy should be used.


On the Reactivity of a NHC Nickel Bis-Boryl Complex: Reductive Elimination and Formation of Mono-Boryl Complexes.
The synthesis of the first terminal mono-boryl complexes of nickel, which are not stabilized by a pincer ligand, is reported. The reaction of the nickel bis-boryl complex cis-[Ni(i Pr2 ImMe )2 (Bcat)2 ] 1 (cat=1,2-O2 C6 H4 ) with the small donor ligand PMe3 led to a complete ligand exchange at nickel with reductive elimination of B2 cat2 and formation of the bis-NHC adduct [B2 cat2 ⋅ (i Pr2 ImMe )2 ] 3 and [Ni(PMe3 )4 ] 2 as the metal-containing species. Electrophilic attack of MeI on complex 1 or ligand dismutation of 1 with trans-[Ni(i Pr2 ImMe )2 Br2 ] led to loss of only one boryl ligand of 1 and afforded the nickel mono-boryl complexes trans-[Ni(i Pr2 ImMe )2 (Bcat)Br] 4 a and trans-[Ni(i Pr2 ImMe )2 (Bcat)I] 4 b.


Classification Differences in Food Insecurity Measures between the United States and Canada: Practical Implications for Trend Monitoring and Health Research.
Food insecurity, inadequate access to food due to financial constraints, is a major public health issue in the United States and Canada, where the same 18-item questionnaire is used to monitor food insecurity. Researchers often assume that findings on food insecurity from the 2 countries are comparable with each other, but there are between-country differences in how food insecurity status is determined. We aimed to compare the distribution of household food insecurity in the Canadian population applying the US and Canadian classification schemes. We also examined the extent to which associations between food insecurity and adults' health differ under the 2 schemes. We used the population-representative Canadian Community Health Survey 2005-2017 linked to administrative health records. Food insecurity was measured by the Household Food Security Survey Module. Adults 18 y and older with valid food insecurity status were included from all jurisdictions except Quebec (n = 403,200). We cross-tabulated food insecurity status classified by the US and Canadian schemes. We also fitted logistic regressions on self-reported and objective health measures adjusting for confounders. Applying the Canadian classification scheme, 7.7% of households were food insecure; the number fell to 6.0% with the US scheme. Associations between food insecurity status and health measures were mostly similar across classification schemes, although the associations between food insecurity and self-reported health were slightly larger if the US scheme was applied. Marginal food security/insecurity was associated with worse health measures irrespective of the classification scheme. United States-Canada discordance in classification of marginal food security/insecurity had a limited effect on health prediction. United States-Canada differences in classification affected the apparent distribution of household food insecurity but not the associations between food insecurity and measures of adult health. Marginal food security/insecurity should be set apart from the food-secure group for trend monitoring and health research.


Low-profile primary stent placement for the treatment of focal calcified ulcerated stenosis in the infrarenal aorta.
To analyze the immediate and midterm success of low-profile stent placement in calcified ulcerated lesions of the infrarenal aorta in patients with arterial occlusive disease. In this prospective case series, 13 symptomatic patients (eight men, five women; mean age, 64.8 years +/- 12.1; age range, 44-84 years) with focal calcified ulcerated stenoses of the infrarenal aorta were treated with stent placement by using a low-profile technique in a radiology intervention center during a 4-year period. Clinical examinations and duplex ultrasonography were used to evaluate the stents? patency and clinical success. Kaplan-Meier graphs were calculated to analyze the freedom-of-symptom rate. The initial technical success rate was 92% (12 of 13 patients). Due to extended calcifications, a residual stenosis of 50%-60% remained in one patient. No peri-interventional complications occurred. The mean follow-up was 26 months (range, 5-53 months). During follow-up, one patient had a restenosis after 7 months and presented clinically with Fontaine stage IIb. Two patients had iliac and/or femoral stenoses, and both presented with Fontaine stage IIb. One patient's symptoms originated from the lumbar spine. Primary patency and primary clinical success rates were 85% and 69%, respectively. According to Kaplan-Meier tables, the freedom-from-symptom rates were 92%, 84%, 73%, and 63% at 0, 7, 12, and 21 months, respectively. Low-profile stent placement in calcified, ulcerated lesions of the infrarenal aorta is an effective and safe treatment for symptomatic stenoses in patients with arterial occlusive disease after a mean follow-up of 26 months.


Protective effects of Polygalae root in experimental TNBS-induced colitis in mice.
In this study, the protective effect of Polygalae root was evaluated in a murine model of experimental colitis by intrarectal injection with 2,4,6-trinitrobenzene sulfonic acid (TNBS). Polygalae root, given orally at 2, 4 g/kg body weight of herbs once a day consecutively for 9 days, could recover the lost body weight and decrease the gross rectal bleeding. Polygalae root also reduced the degree of inflammation and improved significantly the histological changes such as infiltration by polymorphonuclear leukocytes and multiple erosive lesions. Furthermore, the cytokine production of intraepithelial lymphocytes was analyzed. The results showed that IFN-gamma was increased, but IL-4 was decreased in TNBS-induced colitis, when those were compared with the sham controls. But the administration of Polygalae root to TNBS-induced colitis mice showed lower production of IFN-gamma and higher production of IL-4 than the TNBS-induced colitis. These results suggest that the protective effects of Polygalae root against the TNBS colitis may be associated with the regulation of cytokine production of intraepithelial lymphocytes.


Clinical Policy: Use of intravenous tPA for the management of acute ischemic stroke in the emergency department.
This policy was developed by a joint writing panel of the American College of Emergency Physicians and the American Academy of Neurology. The panel reviewed the literature to derive evidence-based recommendations to help clinicians answer the following critical questions: (1) Is intravenous tissue plasminogen activator (tPA) safe and effective for acute ischemic stroke patients if given within 3 hours of symptom onset? (2) Is intravenous tPA safe and effective for acute ischemic stroke patients treated between 3 to 4.5 hours after symptom onset? Evidence was graded and recommendations were given based on the strength of the available data in the medical literature.


Crh and Oprm1 mediate anxiety-related behavior and social approach in a mouse model of MECP2 duplication syndrome.
Genomic duplications spanning Xq28 are associated with a spectrum of phenotypes, including anxiety and autism. The minimal region shared among affected individuals includes MECP2 and IRAK1, although it is unclear which gene when overexpressed causes anxiety and social behavior deficits. We report that doubling MECP2 levels causes heightened anxiety and autism-like features in mice and alters the expression of genes that influence anxiety and social behavior, such as Crh and Oprm1. To test the hypothesis that alterations in these two genes contribute to heightened anxiety and social behavior deficits, we analyzed MECP2 duplication mice (MECP2-TG1) that have reduced Crh and Oprm1 expression. In MECP2-TG1 animals, reducing the levels of Crh or its receptor, Crhr1, suppressed anxiety-like behavior; in contrast, reducing Oprm1 expression improved abnormal social behavior. These data indicate that increased MeCP2 levels affect molecular pathways underlying anxiety and social behavior and provide new insight into potential therapies for MECP2-related disorders.


Plasma concentrations of carminomycin and carminomycinol in man, measured by high pressure liquid chromatography.
In 9 patients with advanced malignant disease who received carminomycin (CMM) in an i.v. bolus injection (dose 18 mg/m2), curves of plasma concentrations of CMM and carminomycinol (CMMOH), a metabolite, versus time were constructed. For determination of plasma concentrations, high pressure liquid chromatography was used. For CMM and CMMOH the median areas under the curves (AUC's) were 31 (range 4-57) X 10(-8) mol/Ql/hr (measured over 24 hr) and 100 (range 309-158) X 10(-8) mol/l/hr (measured over 48 hr) respectively. From the data an accumulation of CMMOH in patients receiving treatments separated by brief intervals ban be predicted (half-life time of plasma disappearance for CMMOH was 2 days). Clinical toxicity was lowest in those 3 patients showing the lowest AUC for both CMM and CMMOH.


Isolation from poultry litter and characterization [corrected] of Staphylococcus spp. capable of growth in high phosphate conditions [corrected].
To isolate and characterize micro-organisms from poultry litter capable of growing under phosphate concentrations typical of poultry litter. Poultry litter extracts were plated onto brain-heart infusion medium (BHI) containing an additional 0.75 mol l(-1) phosphate (BHI-P). Colonies were screened for the presence of inclusion granules with five being selected for further study. All strains displayed identical biochemical characteristics consistent with Staphylococcus spp. and grouped with Staphylococcus spp. by comparative 16S rDNA analysis. Thus all five strains were identified as such. All strains displayed elevated intracellular phosphate levels when cultured in BHI-P broth (0.417-0.600 microg phosphate mg(-1) protein) vs BHI broth (0.075-0.093 microg phosphate mg(-1) protein). When grown using an austere semi-defined medium or BHI-P, Staph. sp. #7 displayed similar elevated intracellular phosphate levels compared with growth in BHI. Poultry litter contains novel Staphylococcus spp. capable of robust growth when exposed to phosphate levels comparable with that typically found in poultry litter. Data suggest intracellular phosphate levels in these strains increase in response to increasing phosphate in the medium or austere medium conditions. Intracellular phosphate did not reach levels comparable with known hyper-accumulating micro-organisms. These data suggest poultry litter possesses a resident microflora that thrives and accumulates intracellular phosphate in response to high phosphate conditions.


Thermal ecology of Northern Water Snakes (Nerodia sipedon) in a northern wetland in central Michigan.
Semi-aquatic north-temperate reptiles experience challenging environmental conditions for thermoregulation on both seasonal and daily bases. We studied the thermal biology of north-temperate Northern Water Snakes (Nerodia sipedon) in central Michigan by remote radiotelemetry monitoring of snake body temperature (Tb) using surgically implanted thermally-sensitive radio-transmitters and by measuring operative temperatures (Te) across a range of microhabitats using biophysical models. Our goals included evaluation of thermoregulatory capabilities at a locality that we viewed to be a fine-grained thermal environment, seasonal variations in patterns of thermoregulation, and the effects of sex on thermoregulation. During summer, snakes showed diel Tb cycling apparently using the open Sphagnum mat for late morning warming and shuttling among different microhabitats until early evening when a monotonic decline in Tb ensued and continued through the early morning hours. Snakes attained Tb within their laboratory-determined preferred body temperature range (Tset = 28-33 °C) mostly during late afternoon and with average percentages of Tb values for individual snakes within Tset range when permitted by operative temperatures (Ex) between 68 and 70% of the time depending on method of measurement. Relatively high investment in thermoregulation when thermal conditions were poor occurred only during September but declined thereafter as snakes prepared to overwinter. We did not detect differences in thermoregulation among reproductive females, non-reproductive females, and males. Relative to a population of N. sipedon at a higher latitude in Ontario our snakes showed a relatively high Tset range and thermoregulated more effectively, particularly during the daylight hours. It remains unclear how much inter-population variation in thermoregulation is due to potential adaptations to latitude, to habitat differences, or variations in methodologies.


A multicenter randomized controlled clinical trial of bovine surfactant for prevention of respiratory distress syndrome.
Treatment with bovine surfactant (SF-RI 1) was shown to be efficacious in improving pulmonary function and in increasing survival rate without BPD in very premature infants. Surfactant therapy did not affect the risk of major complications of prematurity.


Genetic evidence for involvement of membrane trafficking in the action of 5-fluorouracil.
To identify novel genes that mediate cellular sensitivity and resistance to 5-fluorouracil (5-FU), we performed a genome-wide genetic screening to identify altered susceptibility to 5-FU by Schizosaccharomyces pombe haploid nonessential gene deletion library containing 3004 deletion mutants. We identified 50 hypersensitive and 12 resistant mutants to this drug. Mutants sensitive or resistant to 5-FU were classified into various categories based on their putative functions. The largest group of the genes whose disruption renders cells altered susceptibility to 5-FU is involved in nucleic acid metabolism, but to our surprise, the second largest group is involved in membrane trafficking. In addition, several other membrane traffic mutants examined including gdi1-i11, ypt3-i5, Δryh1, Δric1, and Δaps1 exhibited hypersensitivity to 5-FU. Furthermore, we found that 5-FU in low concentration that generally do not affect cell growth altered the localization of Syb1, a secretory vesicle SNARE synaptobrevin which is cycled between the plasma membrane and the endocytic pathway. Notably, 5-FU at such low concentration also significantly inhibited the secretion of acid phosphatase. Altogether, our findings revealed the first evidence that 5-FU influences membrane trafficking as the potential underlying mechanism of the drug action.


Salt intake determines retinal arteriolar structure in treatment resistant hypertension independent of blood pressure.
Patients with treatment resistant hypertension are at increased risk of developing cardiovascular end organ damage. The role of sodium in end organ damage is gaining interest and an independent association of sodium and cardiovascular morbidity and mortality has been described. In an observational study including 40 patients with treatment resistant hypertension, we analysed retinal arteriolar structure in vivo as a determinant of remodelling of small resistant vessels (wall/lumen ratio, wall thickness, wall cross section area) using scanning laser Doppler flowmetry and automatic full-field perfusion imaging analysis. Urinary sodium excretion was determined by 24 h urine sample and, in parallel 24 h ambulatory blood pressure was measured. We analysed the association of the retinal arterial structure with urinary sodium excretion and blood pressure. Wall to lumen ratio, wall thickness and wall cross section area were strongly associated with urinary sodium excretion but not with 24 h blood pressure. In a multiple regression analysis including urinary sodium excretion, BMI, age and 24 h blood pressure, urinary sodium excretion emerged as the only independent determinant of wall thickness (β=0.432, p=0.01), and wall cross section area (β=0.439, p=0.008). Our results clearly demonstrate that salt intake influences the structure of retinal arterioles independent of blood pressure in treatment resistant hypertension. Considering the morphologic relation of retinal arteriolar and cerebral vascular structure these results might prove to have important implications on risk stratification in patients with treatment resistant hypertension.


Anatomic grading of nerve sparing during robot-assisted radical prostatectomy.
Because of the lack of intraoperative visual cues, the amount of nerve sparing (NS) intended by the surgeon does not always correspond to what is actually performed during surgery. Describe a standardized NS grading system based on intraoperative visual cues. A total of 133 consecutive patients who underwent robot-assisted radical prostatectomy (RARP) by a single surgeon were evaluated. The surgeon intraoperatively graded the NS independently for either side as follows: 1=no NS; 2=<50% NS; 3=50% NS; 4=75% NS; 5= ≥ 95% NS. RARP; detailed description of a five-point NS grading system. The area of residual nerve tissue on prostatectomy specimens was compared with the intraoperative NS score (NSS). The rate of positive surgical margins (PSMs) according to the NSS is also reported. In all, 52.6% of operated sides (140 of 266 sides) had NSS 5, 30.1% (80 of 266) had NSS 4, 2.3% (6 of 266) had NSS 3, 13.2% (35 of 266) had NSS 2, and 1.9% (5 of 266) had NSS 1. The area of residual nerve tissue was significantly different among the different NSSs: median area (interquartile range) for NSS 5: 0.5 (0-2) mm(2); for NSS 4: 3 (0-8) mm(2); for NSS 3: 13 (7-23) mm(2); for NSS 2: 14 (8-24) mm(2); and for NSS 1: 57 (56-165) mm(2) (p<0.001). Overall, 9.02% of the patients (12 of 133 patients) had a PSM, with 8.3% (9 of 108) for pT2 and 12% (3 of 25) for pT3. Side-specific PSMs according to NSS were 3.6% (5 of 140) for NSS 5, 7.5% (6 of 80) for NSS 4, 16.7% (1 of 6) for NSS 3, 5.7% (2 of 35) for NSS 2, and 0% (0 of 5) for NSS 1. A limitation of our study is that the key anatomic landmarks are not recognizable in every case, and this technique might not be easy to perform during the early learning curve. We believe that the visual cues exposed in this article will help surgeons achieve more consistent NS during RARP.


The prevalence of factor V R506Q mutation-Leiden among apparently healthy Lebanese.
Resistance to activated protein C (APC) degradation caused by a specific point mutation in the factor V (FV) gene, FV:R506Q or FV-Leiden, which replaces Arg506 with Gln at the APC cleavage site within the FV gene, is the most prevalent inherited caused of venous thrombosis. Recent reports suggested that the prevalence of FV-Leiden is high among Caucasians, and very low among non-Caucasians, thereby suggesting that FV-Leiden has originated as a single event in a primary focus. Insofar as FV-Leiden is associated with increased risk of thromboembolic diseases, coupled with its selective worldwide distribution, the aim of this study was to determine the prevalence of FV-Leiden in Lebanon and compare it with those of other countries of Caucasian and non-Caucasian origin. FV-Leiden was determined by PCR, followed by hybridization with specific wild-type and mutant DNA probes. By screening 174 healthy Lebanese subjects, 25 were shown to carry the FV-Leiden mutation, giving an allele frequency of 7.4% and an overall prevalence rate of 14.4%. Of the 25 FV-Leiden carriers, 24 were in the heterozygous state while one was in the homozygous states. No statistical difference in the FV-Leiden prevalence was noted with respect to age, gender, or sect. In addition to Lebanon, which had the highest prevalence rate reported thus far (14.4%), a high prevalence of FV-Leiden was reported for Syria (13.6%), Greece-Cyprus (13.4%), and Jordan (12.3%), an indication that the Eastern Mediterranean is the primary focus of FV-Leiden mutation. The high prevalence of FV-Leiden in Lebanon suggests that screening for this mutation must be considered for those with a family history, and/or those with additional risk factors for venous thrombosis.


Selective isolation and ansamycin-targeted screenings of commensal actinomycetes from the "maytansinoids-producing" arboreal Trewia nudiflora.
To verify the hypothesis on the involvement of commensal actinomycetes in the biosynthesis of plant maytansinoids that belong to the ansamycin family, selective isolation and targeted screenings were conducted. In total, 164 endophytic actinomycetes isolates were obtained from the roots, twigs, seeds, callus, and germ-free seedlings of "maytansinoids-producing" Trewia nudiflora Linn. by selective isolation methods. Crude extracts of the isolates were screened by antifungal bioassay against Penicillium avellaneum UC-4376, thin-layer chromatography, and liquid chromatography-mass spectrometry detection according to the bioactivity as well as structural characteristics of maytansinoids. Respectively, 25.0%, 64.8%, and 26.7% of the extracts were positive in corresponding screenings. Ten isolates showed positive results in all three different screenings. To confirm on a genetic level, 28 representative isolates from 20 morphological groups were screened by polymerase chain reaction with 3-amino-5-hydroxybenzoic acid synthase gene and carbamoyltransferase gene primers, both of which were involved in the biosynthesis of ansamycins. According to the results of the targeted screenings, two isolates Streptomyces sp. 5B and Streptomyces sp. M27m3 might have the potential of producing ansamycins, which further enhanced the hypothesis that endophyte(s) might be involved in the biosynthesis of plant maytansinoids.


Purging of leukemia-contaminated bone marrow grafts using suicide adenoviral vectors: an in vivo murine experimental model.
Autologous bone marrow transplantation is an alternative therapeutic option for acute myeloid leukemia patients lacking a compatible donor. However, bone marrow from these patients may contain residual leukemic cells that should be ideally eliminated prior to the infusion of the graft. With the aim of developing more efficient protocols of graft purging, adenoviral-mediated gene transfer protocols have been conducted. We studied whether suicide adenoviral vectors expressing the cytosine deaminase gene (AdCD) could be used for selectively killing leukemic WEHI-3B cells. The AdCD transduction followed by the 5-fluorocytosine exposure abrogated the growth of WEHI-3B cells in vitro, with a minimal effect on normal hematopietic progenitors. To test the efficacy of the purging protocol in vivo, bone marrow cells were mixed with syngenic WEHI-3B cells and this chimeric cell population was transduced with AdCD vectors. Infected cells were injected into myeloablated Balb-c mice, which then received a 5-fluorocytosine treatment for 4 days. All mice transplanted with unpurged bone marrow developed leukemia and died. However, 90% of recipients receiving the purging treatment were healthy up to 9 months post-transplantation and had a perfectly re-established hematopoietic system, without any signal of leukemic cell presence. In conclusion, suicide adenoviral vectors are proposed as a tool for the purging of Adenoviral-susceptible myeloid leukemia cells contaminating autologous bone marrow grafts.


When fertile, women seek status via prestige but not dominance.
Biological predictors of human dominance are hotly contested, with far-reaching implications for psychological sex differences and the placement of men and women in the social hierarchy. Most investigations have focused on dominance in men and testosterone, with diminished attention paid to dominance in women and other biological mechanisms. Investigating biological influences on other routes to status attainment popular among women-such as via prestige in addition to dominance-have also been neglected. Here, I examined whether status seeking via prestige and via dominance covaried with fertility probability in a citizen science project spanning 14 countries and 4 world regions. Across 4,179 observations, participants tracked their menstrual cycle characteristics, motivation for prestige and dominance, dominance contest outcomes, and three domains of self-esteem. Self-esteem is predicted by status within a group and helps individuals navigate social hierarchies. Bayesian mixed models controlling for menstruation indicated that the motivation to obtain status via prestige but not dominance peaked when conception was most likely, as did dominance contest losses and two self-esteem domains. Fertility appears to reorient female psychology toward prestige-based strategies to success, enhancing women's desire for social capital through influence and admiration but not through fear, coercion, or intimidation. These insights fundamentally advance the understanding of the biological correlates of status seeking among women. They further suggest that fertility motivates not only mating competition but gaining rank and positive regard in social hierarchies.


Identification of amino acid residues participating in the energy coupling and proton transport of Streptomyces coelicolor A3(2) H+-pyrophosphatase.
The H(+)-translocating inorganic pyrophosphatase is a proton pump that hydrolyzes inorganic pyrophosphate. It consists of a single polypeptide with 14-17 transmembrane domains (TMs). We focused on the third quarter region of Streptomyces coelicolor A3(2) H(+)-pyrophosphatase, which contains a long conserved cytoplasmic loop. We assayed 1520 mutants for pyrophosphate hydrolysis and proton translocation, and selected 34 single-residue substitution mutants with low substrate hydrolysis and proton-pump activities. We also generated 39 site-directed mutant enzymes and assayed their activity. The mutation of 5 residues in TM10 resulted in low energy-coupling efficiencies, and mutation of conserved residues Thr(409), Val(411), and Gly(414) showed neither hydrolysis nor pumping activity. The mutation of six, five, and four residues in TM11, 12, and 13, respectively, gave a negative effect. Phe(388), Thr(389), and Val(396) in cytoplasmic loop i were essential for efficient H(+) translocation. Ala(436) and Pro(560) in the periplasmic loops were critical for coupling efficiency. These low-efficiency mutants showed dysfunction of the energy-conversion and/or proton-translocation activity. The energy efficiency was increased markedly by the mutation of two and six residues in TM9 and 12, respectively. These results suggest that TM10 is involved in enzyme function, and that TM12 regulate the energy-conversion efficiency. H(+)-pyrophosphatase might involve dynamic linkage between the hydrophilic loops and TMs through the central half region of the enzyme.


Primary mixed germ cell tumor arising in the pancreatic head.
Germ cell tumors, comprised of gonadal and extra-gonadal types, are relatively rare tumors arising from primordial germ cells. Extra-gonadal germ cell tumors have been reported to occur at many non-gonadal locations, from the brain to the sacrococcygeal region. However, primary germ cell tumors in the pancreas are extremely rare. Herein, we present the first case of a 12-month-old girl with a primary mixed germ cell tumor, consisting of both endodermal sinus tumor and mature teratoma, in the pancreatic head.


Determination of ticlopidine in human plasma by capillary gas chromatography with ion trap detection.
A gas chromatographic method for determination of ticlopidine in human plasma using mass spectrometric detection was developed. A Perkin Elmer model 8500 gas chromatograph coupled to an ion trap detector (ITD) in electron impact mode (EI) was used. The gas chromatograph was fitted with a 30 m x 0.32 mm i.d., DB-17 capillary column with a film thickness of 0.25 microm. The compounds were isolated from plasma by Extrelut-1 solid-phase extraction using hexane as the solvent of elution. The detection and quantification limits for this method were 0.005 and 0.01 microg/ml, respectively. The calibration curves were linear from 0.01 and 2.5 microg/ml. Recoveries from human plasma spiked at 0.01 and 2.0 microg/ml ranged from 84.4 and 87.3%. The coefficient of variation (CV) was between 5.1 and 6.9%. The results show that the sensitivity, accuracy and precision of the method are adequate for the determination of ticlopidine in human plasma samples. The ITD in SIM mode allows the unequivocal identification of ticlopidine. The suitability of this method was evaluated in the determination of ticlopidine in plasma from healthy volunteers following oral administration of a dose of 500 mg/day.


Diseases among Orang Asli community in Malaysia: a systematic review.
Orang Asli, the indigenous people of Peninsular Malaysia, is a minority population and placed behind in terms of socioeconomy, education and health. The Malaysian government has supported Orang Asli since the second Malaysia Plan in the 1970s, resulting in changes in their living standard, access to health, education and occupation. Hence, this review aims to assess the recent prevalence of diseases among Orang Asli in Peninsular Malaysia. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) review protocol guided this systematic review. The research question was formulated based on Population, Interest, Comparison and Outcome (PICO). The selected databases include Web of Science, Scopus, Ovid and EBSCOhost. The process of identification, screening and inclusion identified 33 articles. The mixed methods appraisal tool (MMAT) was then used to rank the quality of the articles. Selangor is the most frequent state involved in this review (12 studies), followed by Perak (10 studies), Pahang (10 studies) and Kedah (one study). We categorised into four categories of diseases, namely neglected tropical disease (n = 20), non-communicable disease (n = 6), nutritional status (n = 5), and hepatic disease (n = 2). The prevalence of diseases among Orang Asli is higher than in the general population, especially for soil-transmitted helminth (STH) and malnutrition. There is increasing research on non-communicable diseases due to an increasing trend in the socioeconomic status and lifestyle of the Orang Asli. Government agencies and private organisations must work together to empower Orang Asli with a healthy lifestyle, improve their socioeconomic status, and enhance food security, all of which will improve Orang Asli's health and reduce the prevalence of diseases.


Chromosomal gene controlling symbiotic nitrogen fixation in Rhizobium meliloti L5-30.
Auxotrophic Rhizobium meliloti strain RM 246 carries two independent mutations: in the biosynthesis of cysteine (cys) and symbiotic nitrogen fixation process (fix). These two mutations were mapped by transduction between his-240 and ade-4 markers. Cotransduction frequencies show the following order of genes: his-240 fix-1 cys-246 ade-4.


Bioaffinity chromatography: synergy between interactive chromatography and molecular recognition for the separation and analysis of macromolecules.
Affinity chromatography, commonly regarded as an integral tool in macromolecular separation sciences, also provides an analytical method to study structure-function relationships of macromolecular interaction processes and to design recognition molecules. The latter, as found recently for the case of antisense peptides, may be useful as affinity agents in immobilized forms to effect new types of biomolecular separation.


Clofazimine and B669 inhibit the proliferative responses and Na+, K(+)-adenosine triphosphatase activity of human lymphocytes by a lysophospholipid-dependent mechanism.
The relationship between the phospholipase-stimulating and immunosuppressive properties of the riminophenazine anti-mycobacterial agent clofazimine and its experimental analogue, B669, has been investigated in vitro. At concentrations of 0.6 microM and upwards, both riminophenazines, particularly B669, caused dose-related inhibition of mitogen- and alloantigen-stimulated uptake of tritiated thymidine by human mononuclear leucocytes (MNL), while in short-term assays both agents increased the release of lysophosphatidylcholine (LPC) and arachidonic acid from these cells. Arachidonate per se at a concentration of 20 microM did not affect mitogen-activated lymphocyte proliferation, while cyclooxygenase and 5'-lipoxygenase inhibitors, as well as water- and lipid-soluble oxidant-scavengers and anti-oxidant enzymes, failed to protect the cells against the anti-proliferative effects of clofazimine and B669. However, LPC caused dose-related inhibition of lymphocyte proliferation. Moreover, co-incubation of NML with alpha-tocopherol (vitamin E), a lysophospholipid complex-forming agent, or with lysophospholipase, protected the cells against clofazimine and B669, as well as against LPC. Na+, K(+)-adenosine triphosphatase was identified as the primary target of riminophenazine/LPC-mediated inhibition of lymphocyte proliferation. Excessive release of anti-proliferative lysophospholipids during clofazimine or B669 treatment of mitogen- or antigen-activated lymphocytes is the probable biochemical mechanism of the immunosuppressive activity of these agents.


Urolithiasis associated with hypercalciuria.
Fifty male patients with urolithiasis (UL), associated with idiopathic hypercalciuria (IH), were studied in comparison to a group of 18 male normocalcemic patients with inactive calcium stone disease of unknown etiology. In the group of IH-UL, in addition to hypercaliuria, statistically significant hyperphosphaturia with decreased tubular reabsorption of phosphate and hyperuricemia were observed; there was a tendency to hypophosphatemia although non-significant. In 36% of the IH-UL patients the first episode of renal colic appeared at age 40 to 50. Thirty-eight per cent of the IH-UL patients had recurrent stone formation. Twenty per cent of the IH-UL patients had a family history of urolithiasis. Forty-six per cent of all stones contained oxalate in addition to calcium, and 25% of the stones contained oxalate and phosphate.


The mechanism of xylans removal during hydrothermal pretreatment of poplar fibers investigated by immunogold labeling.
Hydrothermal pretreatment initially removed the lignin-free xylan from the middle layer of secondary wall, followed by the lignin-bound xylan, but the cellulose-bound xylan was seldom removed by this pretreatment. An in-depth understanding of the mechanism of xylan removal during hydrothermal pretreatment (HTP) of wood is critical for cost-effective conversion of lignocellulosic biomass to biofuels. Several studies demonstrated the kinetics and mechanism of xylan removal during HTP on molecular scale, but the dissolution mechanism of xylan during HTP remains unclear at ultra-structural level. Our study investigated changes in the micro-distribution of xylan in poplar fiber cell walls during HTP by transmission electron microscopy (TEM) in combination with immunogold labeling. The study revealed that HTP caused greater decline in the density of xylan labeling in the S2 layer of fiber wall than in the S1 layer. There was a greater loss in the density of xylan labeling during HTP in the delignified and enzymatically treated fibers compared to untreated fibers. We propose that in the initial stages of HTP lignin-free xylan in the S2 layer was more readily hydrolyzed than in the S1 layer by hydronium ions. With increasing pretreatment time, the xylan covalently bound to lignin was also removed from the S2 layer due to the dissolution of lignin. The xylan tightly bound to cellulose was seldom removed during HTP, but was hydrolyzed in subsequent enzymatic treatment. This TEM-immunolabeling investigation reveals the manner in which different xylan fractions are removed from fiber cell wall during HTP, and we expect the information to be helpful in developing processes tailored for more effective conversion of cellulosic biomass into fermentable sugars.


Sexual transmission of hepatitis C virus: cohort study (1981-9) among European homosexual men.
To determine the prevalence, incidence, and persistence of positivity for antibodies to hepatitis C virus (anti-HCV) and the potential for sexual transmission of the virus. A cohort analysis covering 1981-9 comparing estimated cumulative incidences of and seroconversion rates for anti-HCV with those of hepatitis B core antibody (anti-HBc) and antibodies to the human immunodeficiency virus (anti-HIV). Copenhagen and Aarhus, Denmark. 259 Male members of a Danish homosexual organisation. Correlations of prevalence and incidence with a wide range of sexual lifestyle variables. Only four (1.6%) subjects were positive for anti-HCV in 1981. The estimated cumulative incidence of positivity for anti-HCV was 4.1% in 1984 (seroconversion rate during 1981-4 (2.5%)) and remained at 4.1% in 1989 (seroconversion rate nil during 1984-9). In contrast, positivity for anti-HBC rose from 44.0% in 1981 to 52.7% in 1984 (seroconversion rate 15.5%) and 58.8% in 1989 (seroconversion rate 12.9%), and that for anti-HIV rose from 8.8% to 24.0% (seroconversion rate 16.7%) and 30.1% (seroconversion rate 8.0%) respectively. Three anti-HCV positive patients seroreverted three to five years later. None of the anti-HCV positive subjects had had a transfusion and only one gave a past history of intravenous drug use. Variables in sexual lifestyle correlated with the presence of anti-HBc but not with that of anti-HCV. In contrast with hepatitis B virus and HIV, sexual transmission of hepatitis C virus seems to be a rare event. Furthermore, antibodies to the virus may become undetectable after several years.


Damage of the endothelial glycocalyx in chronic kidney disease.
The endothelial glycocalyx (eGC), a mesh of anionic biopolymers covering the luminal surface of endothelial cells, is considered as an intravascular compartment that protects the vessel wall against pathogenic insults in cardiovascular disease. We hypothesized that chronic kidney disease (CKD) is associated with reduced eGC integrity and subsequent endothelial dysfunction. Shedding of two major components of the eGC, namely syndecan-1 (Syn-1) and hyaluronan (HA), was measured by ELISA in 95 patients with CKD (stages 3-5) and 31 apparently healthy controls. Plasma levels of Syn-1 and HA increased steadily across CKD stages (5- and 5.5-fold, respectively P < 0.001) and were independently associated with impaired renal function after multivariate adjustment. Furthermore, Syn-1 and HA correlated tightly with plasma markers of endothelial dysfunction such as soluble fms-like tyrosine kinase-1 (sFlt-1), soluble vascular adhesion molecule-1 (sVCAM-1), von-Willebrand-Factor (vWF) and angiopoietin-2 (P < 0.001). Experimentally, excessive shedding of the eGC, evidenced by 11-fold increased Syn-1 plasma levels, was also observed in an established rat model of CKD, the 5/6-nephrectomized rats. Consistently, an atomic force microscopy-based approach evidenced a significant decrease in eGC thickness (360 ± 79 vs. 157 ± 29 nm, P = 0.001) and stiffness (0.33 ± 0.02 vs. 0.22 ± 0.01 pN/nm, P < 0.001) of aorta endothelial cell explants isolated from CKD rats. Our findings provide evidence for damage of the atheroprotective eGC as a consequence of CKD and potentially open a new avenue to pathophysiology and treatment of cardiovascular disease in renal patients.


Valorisation of mixed bakery waste in non-sterilized fermentation for L-lactic acid production by an evolved Thermoanaerobacterium sp. strain.
In this study, an advanced biorefinery technology that uses mixed bakery waste has been developed to produce l-lactic acid using an adaptively evolved Thermoanaerobacterium aotearoense LA1002-G40 in a non-sterilized system. Under these conditions, mixed bakery waste was directly hydrolysed by Aspergillus awamori and Aspergillus oryzae, resulting in a nutrient-rich hydrolysate containing 83.6g/L glucose, 9.5 g/L fructose and 612 mg/L free amino nitrogen. T. aotearoense LA1002-G40 was evaluated and then adaptively evolved to grow in this nutrient-rich hydrolysate. Using a 5-L fermenter, the overall lactic acid production from mixed bakery waste was 0.18 g/g with a titer, productivity and yield of 78.5 g/L, 1.63 g/L/h and 0.85 g/g, respectively. This is an innovative procedure involving a complete bioconversion process for l-lactic acid produced from mixed bakery waste under non-sterilized conditions. The proposed process could be potentially applied to turn food waste into l-lactic acid in an economically feasible way.


The "volumetric" pulsatility index as evaluated by spatiotemporal imaging correlation (STIC): a preliminary description of a novel technique, its application to the endometrium and an evaluation of its reproducibility.
We propose new volumetric indices derived from three-dimensional (3-D) power Doppler (PD) using spatiotemporal imaging correlation (STIC) to overcome the influence of machine settings and attenuation. In this study, we describe these indices and evaluate their interobserver reliability: two static-3-D and two STIC PD datasets were acquired from 60 women and two observers (blinded analysis) evaluated vascularization index (VI), the flow index (FI) and the vascularization flow index (VFI) of standardized spherical samples of endometrium. Three new indices were determined based on maximum, minimum and mean values (vPI, vRI(max-min), vS/D(max-min)) and two indices from frames subjectively defined as systole and diastole (vRI(sys-dia), vS/D(sys-dia)). Highest intraclass coefficient correlations (ICCs) were obtained from vPI derived from VI or VFI (0.77-0.76), followed by vRI(max-min) (0.72-0.72) and vS/D(max-min) (0.52-0.49). ICCs from indices based on subjectively systole and diastole or FI were consistently lower (<0.40). We conclude that the subjective choice of systolic and diastolic frames only lacks reliability but indices based on complete evaluation may reliably be used.