Concomitant vascular and neurodegenerative pathologies double the risk of dementia.
The relative contributions of vascular and degenerative pathology to dementia are unknown. We aim to quantify the proportion of dementia explained by potentially preventable vascular lesions. We systematically searched for population-based cohorts before February 2017 reporting clinicopathological data for individuals with and without dementia. We calculated the summary proportion and absolute risk of dementia comparing subjects with and without the pathology. We identified 10 studies comprising 2856 subjects. Vascular-type pathology and mixed pathology are respectively two and three times more likely in demented patients. The summary proportion of dementia is 77%-86% in subjects with mixed degenerative and vascular pathology and 45% in subjects with pure Alzheimer-type pathology. Patients with mixed pathologies have nearly twice the incremental risk of dementia compared with patients with only Alzheimer-type lesions. Consequently, many cases of dementia could be prevented or delayed by targeting the vascular component.


Preoperative tattooing and improved lymph node retrieval rates from colectomy specimens in patients with colorectal cancers.
India ink tattooing at the time of colonoscopy increases the yield of lymph nodes found in pathological analysis of colectomy specimens. Retrospective study. Virginia Mason Medical Center, Seattle, Washington. Two hundred nine patients with colorectal cancers underwent surgical resections between April 5, 2006, and June 25, 2009, at one institution. A retrospective review of a prospectively collected database was performed, with review of pathology reports for all cases. Adequate lymph node analysis was defined as evaluation of at least 12 lymph nodes. Of 209 patients undergoing resections, 174 had colonic neoplasms, and 35 had rectal neoplasms. Sixty-two of 174 patients with colon cancer had India ink tattooing at the time of colonoscopy. The mean (range) numbers of lymph nodes examined in tattooed and nontattooed specimens were 23 (7-77) and 19 (2-74), respectively (P = .03). At least 12 lymph nodes were analyzed for 87.1% of the tattooed specimens compared with 72.3% of the nontattooed specimens (P = .02). Eight of 35 patients with rectal cancer had India ink tattooing at the time of colonoscopy. Fifty-four percent of patients with rectal cancer had undergone neoadjuvant chemoradiotherapy. The median numbers of lymph nodes examined in tattooed and nontattooed specimens were 19 and 16, respectively. Tattooing of colonic lesions at the time of preoperative colonoscopy seems to increase the quality of lymph node analysis. We advocate routine tattooing of all suspicious neoplasms at the time of colonoscopy.


Single versus multicomponent intervention in frail elderly: simplicity or complexity as precondition for success?
Research on geriatric syndromes has helped to clarify risk factors and established effective intervention strategies, yet the results based on this evidence have mostly failed to translate into clinical practice. The translation of geriatric syndrome research into practice faces unique challenges, which may heighten the barriers to evidence-based implementation. The British Medical Research Council framework (MRC) for development and evaluation of complex interventions, turns out to be very valuable in developing and evaluating interventions in the complex clinical reality of geriatrics. This paper illustrates the different phases of this framework on the basis of examples from geriatric research projects in The Netherlands. The discussed barriers in complex interventions can be mapped using the different phases in the MRC-framework and thus become feasible challenges for good quality research.


Beta-lactam monotherapy or combination therapy for bloodstream infections or pneumonia due to Pseudomonas aeruginosa: a meta-analysis.
To compare the clinical and microbiological outcomes of patients treated with beta-lactam monotherapy or combination therapy for Pseudomonas aeruginosa infections. MEDLINE, Google Scholar and the Cochrane Library. Experimental and observational studies published as full papers up to December 2020 that compared the efficacy of beta-lactams used as monotherapy or in combination with other active agents as empirical or targeted therapy for bloodstream infections or hospital-acquired pneumonia/ventilator-associated pneumonia due to P. aeruginosa were included in this meta-analysis. The outcomes evaluated were in-hospital mortality rate, 14-day- or 30-day-mortality rate, microbiological cure rate and clinical cure rate. Of 8363 citations screened, six randomized controlled trials, six prospective cohort studies and 21 retrospective cohort studies were included in the analysis, accounting for a total of 3861 subjects. Considering the 14 studies evaluating empirical therapy, no significant difference in mortality rate was observed between the two groups [relative risk (RR) 1.06, 95% confidence interval (CI) 0.86-1.30; P=0.6]. Similar findings were obtained among the 18 studies analysing targeted therapy (RR 1.04, 95% CI 0.83-1.31; P=0.708); however, grouping the studies by design, higher mortality was observed among patients receiving monotherapy in five prospective studies (RR 1.37, 95% CI 1.06-1.79; P=0.018). Finally, no difference was observed between groups in terms of microbiological cure and clinical cure. This meta-analysis demonstrated no difference in mortality rate, clinical cure rate and microbiological cure rate in patients treated with beta-lactam monotherapy or combination therapy for P. aeruginosa infections.


The effectiveness of essential oil from Citrus limon peel on Candida albicans biofilm formation: An experimental in vivo study.
Candida albicans is resistant to commercial antifungal agents. Therefore, it is desirable to use material derived from natural sources as an antifungal agent. Essential oil from Citrus limon peel is able to inhibit the growth of C. albicans in vitro. The purpose of this study was to determine the most effective concentration of essential oil from C. limon peel with regards to the inhibition of C. albicans cyto-morphometric changes and biofilm formation in vivo. Male Wistar rats weighing 200-300 g were inoculated with C. albicans for 48 h and then given a single dose of oral methylprednisolone as an immunosuppressant. Essential oil from C. limon peel, in a gel form and at three different concentrations (0.39%, 0.78% and 1.56%), was applied twice a day for 2 days. The rats were killed after 48 h and then palatal mucosa tissues were prepared and examined with a scanning electron microscope (SEM) with regards to C. albicans, cyto-morphometric changes and biofilm formation. Essential oil from C. limon peel at a concentration of 1.56% showed the strongest ability to inhibit C. albicans growth when compared to 0.78% and 0.39%. At a concentration of 1.56%, essential oil from C. limon peel disrupted cyto-morphometric changes; cells that were neither in intact nor colonised were evident, the filaments around the cells were smooth, the layer of biofilm had disappeared and there was no evidence of hyphae formation. The effect of essential oil from C. limon peel on cyto-morphometric changes and biofilm formation was concentration-dependent. Essential oil from C. limon peel at a dose of 1.56% showed the strongest ability to inhibit cyto-morphometric changes and biofilm formation. These findings demonstrate that essential oil of C. limon peel is a potential antifungal candidate for the treatment of candidiasis.


Hyperglycemia and cerebral glucose in aneurysmal subarachnoid hemorrhage.
To determine whether hyperglycemia exerts deleterious effects via cerebral energy metabolism and to illuminate the effects of cerebral high/low glucose in patients with aneurysmal subarachnoid hemorrhage. Prospective, nonrandomized single-center study over a 2-year period in an intensive care unit at a primary-level university hospital. 28 subarachnoid hemorrhage patients (age 53 +/- 10 years, WFNS grade 2.8 +/- 1.5) classified as asymptomatic (n = 5) or symptomatic with acute focal or delayed ischemic neurological deficits (n = 23). Hyperglycemia (> 7.8 mmol/l; >140 mg/dl) was more frequent in symptomatic patients and was reflected in higher glycerol concentrations than in asymptomatic patients. In all patients a microdialysis catheter was inserted into the tissue at risk; dialysates were collected hourly for 10 days. Cerebral low-glucose episodes (0.6 mmol/l) and high-glucose episodes (>2.6 mmol/l) occurred independently of blood glucose levels. During high-glucose episodes cerebral microdialysate levels were normal, while cerebral low glucose, occurring more frequently in symptomatic patients, was associated with severe cellular distress (increase in lactate/pyruvate ratio, glutamate, glycerol) and with unfavorable outcome if combined with hyperglycemia. Although hyperglycemia was more frequent in symptomatic patients and associated with high glycerol levels, hyperglycemia was not related to cerebral high glucose. It appears that the association of adverse outcome with acute-phase hyperglycemia is not mediated by cerebral glucose metabolism. Cerebral low glucose was associated with severe metabolic distress and may present a target for therapy to improve clinical outcome.


Contrasting denaturation maps of Xenopus laevis and Xenopus borealis mitochondrial DNAs.
Denaturation maps of mitochondrial DNAs of Xenopus laevis and Xenopus borealis are radically different from each other. This is in striking contrast to the invariant denaturation patterns previously recognized among mtDNAs of various Drosophila species, particularly, since the two toads may be even more closely related to each other than the Drosophila species.


Determination of the equilibrium micelle-inserting position of the fusion peptide of gp41 of human immunodeficiency virus type 1 at amino acid resolution by exchange broadening of amide proton resonances.
The exchange broadening of backbone amide proton resonances of a 23-mer fusion peptide of the transmembrane subunit of HIV-1 envelope glycoprotein gp41, gp41-FP, was investigated at pH 5 and 7 at room temperature in perdeuterated sodium dodecyl sulfate (SDS) micellar solution. Comparison of resonance peaks for these pHs revealed an insignificant change in exchange rate between pH 5 and 7 for amide protons of residues 4 through 14, while the exchange rate increase at neutral pH was more prominent for amide protons of the remaining residues, with peaks from some protons becoming undetectable. The relative insensitivity to pH of the exchange for the amide protons of residues 4 through 14 is attributable to the drastic reduction in [OH-] in the micellar interior, leading to a decreased exchange rate. The A15-G16 segment represents a transition between these two regimes. The data are thus consistent with the notion that the peptide inserts into the hydrophobic core of a membrane-like structure and the A15-G16 dipeptide is located at the micellar-aqueous boundary.


Iterative fuzzy segmentation for an accurate delimitation of the breast region.
In mammographic images, extracting different anatomical structures and tissues types is a critical requirement for the breast cancer diagnosis. For instance, separating breast and background regions increases the accuracy and efficiency of mammographic processing algorithms. In this paper, we propose a new region-based method to properly segment breast and background regions in mammographic images. These regions are estimated by an Iterative Fuzzy Breast Segmentation method (IFBS). Based on the Fuzzy C-Means (FCM) algorithm, IFBS method iteratively increases the precision of an initially extracted breast region. This proposal is evaluated using the MIAS database. Experimental results show high accuracy and reliability in breast extraction when compared with Ground-Truth (GT) images.


Is infertility after surgery for cryptorchidism congenital or acquired?
We evaluated whether deletions of the DAZ (deleted in azoospermia) gene, abnormal karyotypes or hypogonadotropic hypogonadism (HH) were demonstrable in infertile men who had undergone surgery in childhood for cryptorchidism with a simultaneous testicular biopsy that demonstrated no or almost no germ cells. In six men with infertility after surgery for cryptorchidism, the adult karyotype and analyses for the DAZ gene, serum follicle-stimulating hormone, luteinizing hormone, and testosterone were performed from a peripheral blood sample. Testicular volume was also measured. All patients exhibited a 46,XY karyotype. There were no deletions of the DAZ-gene, no HH and no testicular atrophy. The infertility was thus not proved to be congenital, and consequently, surgical treatment is indicated before the germ cells disappear from undescended testes. This appears to be before 15 months of age.


Four Loci Are Associated with Cardiorespiratory Fitness and Endurance Performance in Young Chinese Females.
Cardiorespiratory fitness (CRF) and endurance performance are characterized by a complex genetic trait with high heritability. Although research has identified many physiological and environmental correlates with CRF, the genetic architecture contributing to CRF remains unclear, especially in non-athlete population. A total of 762 Chinese young female participants were recruited and an endurance run test was used to determine CRF. We used a fixed model of genome-wide association studies (GWAS) for CRF. Genotyping was performed using the Affymetrix Axiom and illumina 1 M arrays. After quality control and imputation, a linear regression-based association analysis was conducted using a total of 5,149,327 variants. Four loci associated with CRF were identified to reach genome-wide significance (P < 5.0 × 10-8), which located in 15q21.3 (rs17240160, P = 1.73 × 10-9, GCOM1), 3q25.31 (rs819865, P = 8.56 × 10-9, GMPS), 21q22.3 (rs117828698, P = 9.59 × 10-9, COL18A1), and 17q24.2 (rs79806428, P = 3.85 × 10-8, PRKCA). These loci (GCOM1, GMPS, COL18A1 and PRKCA) associated with cardiorespiratory fitness and endurance performance in Chinese non-athlete young females. Our results suggest that these gene polymorphisms provide further genetic evidence for the polygenetic nature of cardiorespiratory endurance and be used as genetic biomarkers for future research.


Binding of Iron (II) Ions by Aqueous Extractions from Yerba Mate (Ilex paraguariensis).
We studied the ability of an aqueous extract from yerba mate and a dry extract obtained on the basis of this aqueous extract to remove Fe(II) ions from an aqueous medium. Aqueous extracts from mate dose-dependently reduced the concentration of free Fe(II) ions assayed by the reaction with 1,10-phenanthroline. This can be attributed to polyphenolic compounds with iron-chelating properties present in aqueous extracts from mate, namely quercetin, rutin, caffeic and chlorogenic acids. These substances effectively removed Fe(II) ions from the medium (the initial concentration of these ions was 15 μM) in the concentration range of 20-30 μM. Binding of Fe(II) ions by aqueous mate extracts (due to the formation of chelate complexes with the participation of polyphenolic compounds) modified their absorption spectra in the visible region. Binding of Fe(II) ions can be a mechanism of the antioxidant action of yerba mate.


Subcutaneous aprotinin causes local hyperaemia. A possible mechanism by which aprotinin improves control in some diabetic patients.
Local changes in blood flow at the subcutaneous injection site of the proteinase inhibitor aprotinin and its diluent were measured by photoelectric plethysmography. Aprotinin, but not its diluent, caused local hyperaemia in five normal subjects and in five stable and five brittle insulin-dependent diabetic patients, local blood flow increasing by 80%-180%. The duration of the hyperaemic response was shorter in the brittle diabetic patients than in the other two groups, but there was wide individual variation. Aprotinin is known to enhance subcutaneous insulin absorption in normal subjects and in some brittle diabetic patients. The basis for this might be through increasing blood flow near the injection site rather than by inhibition of insulin breakdown.


Applications of plant-based fermented foods and their microbes.
Plant-based fermentations and their microbes provide an underexplored source for novel biotechnological applications. Recent advances in DNA sequencing technologies and analyses of sequencing data highlight that a diverse array of lactic acid bacteria (LAB) frequently dominate these plant fermentations. Because of the long history of safe LAB use in fermented foods, we argue here that various novel probiotic, synbiotic and a range of other industrial applications can be produced based on new insights in the functional and genetic potential of these LAB. To aid in this quest, comparative genomics tools are increasingly available enabling a more rational design of wet-lab experiments to screen for the most relevant properties. This is also true for the exploration of useful enzymatic and (secondary) metabolic production capacities of the LAB that can be isolated from these plant-based fermentations, such as the recent discovery of a cellulase enzyme in specific Lactobacillus plantarum group members.


Raynaud's phenomenon in the emergency department.
Raynaud's phenomenon manifests as triphasic color changes of the digits, induced by exposure to low temperature or emotional stress. It is a relatively common disorder, estimated to affect 5% to 10% of the general population and 25% to 30% of otherwise healthy women. Although usually self-limiting, it can be severely painful and debilitating, and complicated by ulcerations and tissue necrosis. For the emergency physician treating a patient with an acute presentation of the phenomenon, the main challenges are to achieve adequate pain control, reverse vasospasm, and maintain viable tissue. Emergency treatment can also extend to patient education and arrangement of appropriate referrals and follow-up care.


Plasma asymmetric dimethylarginine is associated with vulnerable plaque and long-term outcomes in stable coronary artery disease.
Asymmetric dimethylarginine (ADMA) is considered to be an atherogenic molecule. We aimed to investigate the relationship between ADMA and plaque vulnerability assessed by optical coherence tomography (OCT) in patients with stable coronary artery disease (CAD). Two hundred and forty-five patients with stable CAD undergoing OCT-guided percutaneous coronary intervention were included in this study and were divided into two groups according to their ADMA levels. Micro-vessel, macrophage accumulation, thin-cap fibroatheroma, intra-plaque calcium and lipid core content, and vulnerable score (VS) were evaluated by OCT analysis. The patients with higher ADMA levels had significantly higher calcium and lipid content (p < 0.001, respectively). There were significantly more micro-vessel and macrophage (32.8%, p = 0.004 and 52.5%, p < 0.001, respectively) and higher VS (87.7 ± 17.6, p < 0.001) in the higher ADMA group. Moreover, plasma ADMA level was significantly correlated with the intra-plaque lipid, calcium content and VS (p < 0.001, respectively). Plasma ADMA level was identified as an independent predictor of future adverse cardiovascular events, following OCT-guided PCI. In patients with stable CAD, higher plasma ADMA levels were significantly associated with the presence of intra-plaque lipid, calcification, vulnerable plaque, and poor long-term outcomes.


Severe ischemia of the hand following intra-arterial promazine injection: effects of vasodilation, anticoagulation, and local thrombolysis with tissue-type plasminogen activator.
Promazine hydrochloride was injected accidentally in the antecubital artery of a 42-year-old woman, resulting in severe ischemia of the second and third fingers of her right hand which lasted for four days before she was hospitalized. Vasodilation by combining axillary plexus block and intravenous sodium nitroprusside did not improve ischemia and local thrombolysis was performed using recombinant tissue-type plasminogen activator (50 mg over 8 hours), resulting in normalization of digital pressure in one of the two affected fingers. The outcome was favourable and amputation could be avoided.


Mobility and equipment for the ventilator-dependent tetraplegic.
The opportunity to realistically equip the ventilator-dependent tetraplegic to return to his community can be met by a concerned team in specialised spinal cord injury centres. Proper equipment, independent electric wheelchair mobility and family training, encourages acceptance of the ventilator-dependent quadriplegic and increases his life-style options. Ideally, the initial 6-month medical management and rehabilitation programme is followed by periodic re-evaluations for medical follow-up, equipment changes and functional upgrading. The medical community must continue to respond to the challenge to offer adequate living facilities and financial resources for equipment and programme development.


Genetic and Phenotypic Variation of Campylobacter jejuni NCTC11168 Caused by flhA Mutation during Laboratory Passage.
Campylobacter jejuni NCTC11168 is commonly used as a standard strain for flagellar biosynthesis research. In this report, two distinguished phenotypic isolates (CJ1Z, flhA mutant strain, lawn; CJ2S, flhA complemented strain, normal colony) appeared during laboratory passages for NCTC11168. Phenotypic assessments, including motility plates, transmission electron microscopy, biofilm formation assay, autoagglutination assay, and genome re-sequencing for these two isolates (CJ1Z, flhA mutant strain; CJ2S, flhA complemented strain) were carried out in this study. Transmission electron microscopy revealed that the flagellum was lost in CJ1Z. Phenotypic assessments and genome sequencing of the two isolates were performed in this study. The capacity for biofilm formation, colony auto-agglutination, and isolate motility was reduced in the mutant CJ1Z. Comparative genomic analysis indicated a unique native nucleotide insertion in flhA (nt, 2154) that caused the I719Y and I720Y mutations and early truncation in flhA. FlhA has been found to influence the expression of flagella in C. jejuni. To the best of our knowledge, this is the first study to describe the function of the C-terminal of this protein.


International trials and national practice: a questionnaire survey of current physician practice in the treatment of acute myocardial infarction.
To establish current national clinical practice in the care of patients with acute myocardial infarction (AMI), a questionnaire survey of 50 consultant physicians currently working in the Republic of Ireland was carried out. There were 45 (90%) respondents. 32/45 (71%) give thrombolysis in CCU only; 13/45 (29%) give thrombolysis in casualty also. Streptokinase (Stk) is the first choice thrombolytic agent for the majority. 14/45 (31%) use tPA for anterior AMI in patients under 60 years. Angiotensin converting enzyme (ACE) inhibitors are given by 34/45 (76%) to patients with evidence of left ventricular dysfunction. ACE inhibitors are neither used routinely nor are they prescribed in the first three days after the AMI by the majority of the physicians surveyed. Serum magnesium is checked routinely by 5/45 (11%) and intravenous magnesium is given routinely by 5/45 (11%). The percentage of AMI patients considered for angiography varied from 10-50%. Despite reports from randomised, controlled trials showing reduced mortality in patients given tPA (versus Stk), routine early ACE inhibition and intravenous magnesium post-AMI, most clinicians in Ireland use streptokinase, selective late ACE inhibition and no magnesium. The reasons for the dichotomy between the favourable results of randomised clinical trials and routine practice are speculative.


Evaluation of a dispensing instrument (Dynatech MIC-2000) for preparing microtiter antibiotic plates and testing their potency during storage.
The MIC-2000 96-channel dispenser was evaluated for accuracy and repeatability of dispensing 50-mul volumes of water. It was found to perform within the manufacturer's specifications for accuracy of +/-5%, but not within the limits for repeatability of +/-1%. Overall, instrument performance was found to be satisfactory for the antimicrobial susceptibility testing technique which has been implemented in this laboratory. A method is suggested for simple evaluation of the volumes dispensed. A variety of antibiotics may be stored in Trypticase soy broth in Microtiter plates without loss of potency for periods of at least 2 weeks at -20 degrees C and 4 months at -70 degrees C.


Ultrastructural localisation of alpha-fetoprotin (AFP) in regenerating mouse liver poisoned with CCL4. 1. Reexpression of AFP in differentiated hepatocytes.
The AFP-synthesizing cells were identified by ultrastructural localization of the antigen in regenerating liver of adult mice after CCl4 poisoning. An indirect immunoperoxidase method with rabbit anti-mouse AFP and peroxidase conjugates of anti-rabbit IgG or their Fab' was used. Good preservation of AFP and tissue structure, and sufficient permeability for the conjugates were obtained after 20' prefixation of small liver specimens in 8% formaldehyde -0.05% glutaraldehyde followed by 16 h fixation in 8% formaldehyde. The intracellular localization of AFP observed in the light microscope in most cases corresponded to its synthesis and secretion. It was found in two cell types, both concentrated mainly in the perinecrotic zones and constituting only a small part of the whole cell population. Most of the AFP-producing cells were normal differentiated hepatocytes without any structural signs of damage. A few smaller cells with active AFP synthesis were present in some animals. By their ultrastructure they resembled the oval cells found during chemical hepatocarcinogenesis in rats.


No effect of Valsalva maneuver or Trendelenburg angle on axillary vein size.
A new technique for establishing ultrasound-guided central access involves the use of the axillary vein, the distal projection of the subclavian vein, via the lateral chest. To examine the effects of Valsalva maneuver and Trendelenburg positioning on axillary vein cross-sectional area (CSA). Using a group-sequential design, we enrolled stable emergency patients and measured their axillary veins sonographically. Patients were measured while supine, then after a Valsalva maneuver, and then at 5°, 10°, 15°, and 17° of Trendelenburg positioning, pausing 2 min after each change. We asked patients to score their discomfort from 0 to 10 in each position. We enrolled 30 adult patients with a median age of 39 years (range, 20-66 years). Treating physicians considered 11 of these patients to have hypovolemia. The Valsalva maneuver decreased CSA (Mean difference = -0.03 cm(2)), (95% confidence interval [CI] -0.10-0.04). Trendelenburg positioning did not statistically increase CSA. The 5° position caused the largest increase, that is, 0.04 cm(2) (95% CI -0.04-0.12) in the entire group and 0.1 cm(2) (95% CI -0.07-0.28) in the hypovolemic subgroup. At greater degrees of Trendelenburg positioning, patients reported higher discomfort scores or simply dropped out. The Valsalva maneuver and Trendelenburg angles above 10° do not increase axillary vein area but do increase patient discomfort. Our data suggest optimal positioning in the supine resting position or at a 5° Trendelenburg position.


Unveiling Nature's potential: Promising natural compounds in Parkinson's disease management.
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Although the exact etiology of PD remains elusive, growing evidence suggests a complex interplay of genetic, environmental, and lifestyle factors in its development. Despite advances in pharmacological interventions, current treatments primarily focus on managing symptoms rather than altering the disease's underlying course. In recent years, natural phytocompounds have emerged as a promising avenue for PD management. Phytochemicals derived from plants, such as phenolic acids, flavones, phenols, flavonoids, polyphenols, saponins, terpenes, alkaloids, and amino acids, have been extensively studied for their potential neuroprotective effects. These bioactive compounds possess a wide range of therapeutic properties, including antioxidant, anti-inflammatory, anti-apoptotic, and anti-aggregation activities, which may counteract the neurodegenerative processes in PD. This comprehensive review delves into the pathophysiology of PD, with a specific focus on the roles of oxidative stress, mitochondrial dysfunction, and protein malfunction in disease pathogenesis. The review collates a wealth of evidence from preclinical studies and in vitro experiments, highlighting the potential of various phytochemicals in attenuating dopaminergic neuron degeneration, reducing α-synuclein aggregation, and modulating neuroinflammatory responses. Prominent among the natural compounds studied are curcumin, resveratrol, coenzyme Q10, and omega-3 fatty acids, which have demonstrated neuroprotective effects in experimental models of PD. Additionally, flavonoids like baicalein, luteolin, quercetin, and nobiletin, and alkaloids such as berberine and physostigmine, show promise in mitigating PD-associated pathologies. This review emphasizes the need for further research through controlled clinical trials to establish the safety and efficacy of these natural compounds in PD management. Although preclinical evidence is compelling, the translation of these findings into effective therapies for PD necessitates robust clinical investigation. Rigorous evaluation of pharmacokinetics, bioavailability, and potential drug interactions is imperative to pave the way for evidence-based treatment strategies. With the rising interest in natural alternatives and the potential for synergistic effects with conventional therapies, this review serves as a comprehensive resource for pharmaceutical industries, researchers, and clinicians seeking novel therapeutic approaches to combat PD. Harnessing the therapeutic potential of these natural phytocompounds may hold the key to improving the quality of life for PD patients and moving towards disease-modifying therapies in the future.


Physicians' knowledge, perceptions, and attitudes toward antimicrobial prescribing in Riyadh, Saudi Arabia.
To assess knowledge, perceptions, and attitudes toward antimicrobial prescribing among physicians practicing in Riyadh, Saudi Arabia. A questionnaire was developed and distributed to physicians working in hospitals in Riyadh, Saudi Arabia between June and August 2013. The results were analyzed using Stata 12 software. Two hundred and twelve (84.8%) full responses were returned. Most respondents perceived antimicrobial resistance as a significant problem in their daily practice (119, 56.1%) and at a national level (148, 69.8%). Inappropriate empirical therapy (101, 47.6%) and excessive use of antimicrobials in healthcare settings (66, 31.1%) were believed to be the main contributors to increasing bacterial resistance. Respondents favor treating infection rather than colonization (98, 46.2%), and physician education (74, 34.9%) as the most effective interventions to reduce antimicrobial resistance. Many respondents (95, 44.8%) do not feel confident in their knowledge of antimicrobial prescribing. Two-thirds of the respondents (135, 63.7%) have local antimicrobial guidelines, of which 90 (66.7%) felt were useful. Most respondents (160, 75.5%) considered their local infectious diseases service to be very helpful. There are considerable unmet training and education need for physicians in the area of antimicrobial prescribing. Local antimicrobial guidelines need revision to ensure they are more relevant and helpful for medical practitioners.


Genotype-dependent sulphite tolerance of Australian Dekkera (Brettanomyces) bruxellensis wine isolates.
The aim of this study was to determine sulphite tolerance for a large number of Dekkera bruxellensis isolates and evaluate the relationship between this phenotype and previously assigned genotype markers. A published microplate-based method for evaluation of yeast growth in the presence of sulphite was benchmarked against culturability following sulphite treatment, for the D. bruxellensis type strain (CBS 74) and a reference wine isolate (AWRI 1499). This method was used to estimate maximal sulphite tolerance for 41 D. bruxellensis isolates, which was found to vary over a fivefold range. Significant differences in sulphite tolerance were observed when isolates were grouped according to previously assigned genotypes and ribotypes. Variable sulphite tolerance for the wine spoilage yeast D. bruxellensis can be linked to genotype markers. Strategies to minimize risk of wine spoilage by D. bruxellensis must take into account at least a threefold range in effective sulphite concentration that is dependent upon the genotype group(s) present. The isolates characterized in this study will be a useful resource for establishing the mechanisms conferring sulphite tolerance for this industrially important yeast species.


Recent Advances in the Therapeutic Strategies of Glioblastoma Multiforme.
Glioblastoma multiforme (GBM) is one of the most common, most formidable, and deadliest malignant types of primary astrocytoma with a poor prognosis. At present, the standard of care includes surgical tumor resection, followed by radiation therapy concomitant with chemotherapy and temozolomide. New developments and significant advances in the treatment of GBM have been achieved in recent decades. However, despite the advances, recurrence is often inevitable, and the survival of patients remains low. Various factors contribute to the difficulty in identifying an effective therapeutic option, among which are tumor complexity, the presence of the blood-brain barrier (BBB), and the presence of GBM cancer stem cells, prompting the need for improving existing treatment approaches and investigating new treatment alternatives for ameliorating the treatment strategies of GBM. In this review, we outline some of the most recent literature on the various available treatment options such as surgery, radiotherapy, cytotoxic chemotherapy, gene therapy, immunotherapy, phototherapy, nanotherapy, and tumor treating fields in the treatment of GBM, and we list some of the potential future directions of GBM. The reviewed studies confirm that GBM is a sophisticated disease with several challenges for scientists to address. Hence, more studies and a multimodal therapeutic approach are crucial to yield an effective cure and prolong the survival of GBM patients.


Tunable Selectivity and High Efficiency of CO2 Electroreduction via Borate-Enhanced Molten Salt Electrolysis.
Converting CO2 into value-added chemical fuels and functional materials by CO2 reduction reaction (CO2RR) is conducive to achieving a carbon-neutral energy cycle. However, it is still challenging to efficiently navigate CO2RR toward desirable products. Herein, we report a facile strategy to extend product species in borate-containing molten electrolyte at a positively shifted cathodic potential with a high current density (e.g. 100 mA/cm2), which can selectively electro-transform CO2 into desired products (either CO or solid carbon nanofibers, respectively reaching a high selectivity of ∼90%). The borates can act as a controller of electrolyte alkalinity to buffer the concentration of sequentially generated O2- during CO2RR, positively shifting the reduction potential of the captured CO2 and concurrently extending the product species. The sustainable buffering effect is available under CO2 atmosphere. Compared with borate-free electrolyte, the CO2 conversion efficiency is over three times higher, while the electrolysis energy consumption is decreased by over 40%.


Changes in rat brain cannabinoid binding sites after acute or chronic exposure to their endogenous agonist, anandamide, or to delta 9-tetrahydrocannabinol.
A brain constituent, the N-amide derivative of arachidonic acid, termed anandamide, has been recently proposed as a possible endogenous ligand for the cannabinoid receptor. The present study has been designed to examine whether the acute or chronic exposure to anandamide affected the binding of cannabinoid receptors in specific brain areas as occurred with the exogenous cannabinoid agonist, delta 9-tetrahydrocannabinol (THC). To this end, we measured the maximum binding capacity (Bmax) and the affinity (Kd) of cannabinoid receptors, by using [3H]CP-55,940 binding assays, in membranes obtained from several brain areas of male rats acutely or chronically treated with anandamide or THC. Results were as follows. The acute administration of either anandamide or THC increased the Bmax of cannabinoid receptors in the cerebellum and, particularly, in the hippocampus. This effect was also observed after 5 days of a daily exposure to either anandamide or THC. However, whereas the increase in the Bmax after the acute treatment seems to be caused by changes in the receptor affinity (high Kd), the increase after the chronic exposure may be attributed to an increase in the density of receptors. On the contrary, the [3H]CP-55,940 binding to cannabinoid receptors in the striatum, the limbic forebrain, the mesencephalon, and the medial basal hypothalamus was not altered after the acute exposure to anandamide or THC. However, the chronic exposure to THC significantly decreased the Bmax of these receptors in the striatum and nonsignificantly in the mesencephalon. This effect was not elicited after the chronic exposure to anandamide and was not accompanied by changes in the Kd.(ABSTRACT TRUNCATED AT 250 WORDS)


Transcriptional regulation of the ADP-glucose pyrophosphorylase isoforms in the leaf and the stem under long and short photoperiod in lentil.
ADP-glucose pyrophosphorylase (AGPase) is a key enzyme in plant starch biosynthesis. It contains large (LS) and small (SS) subunits encoded by two different genes. In this study, we explored the transcriptional regulation of both the LS and SS subunits of AGPase in stem and leaf under different photoperiods length in lentil. To this end, we first isolated and characterized different isoforms of the LS and SS of lentil AGPase and then we performed quantitative real time PCR (qPCR) to see the effect of photoperiod length on the transcription of the AGPase isforms under the different photoperiod regimes in lentil. Analysis of the qPCR results revealed that the transcription of different isoforms of the LSs and the SSs of lentil AGPase are differentially regulated when photoperiod shifted from long-day to short-day in stem and leaves. While transcript levels of LS1 and SS2 in leaf significantly decreased, overall transcript levels of SS1 increased in short-day regime. Our results indicated that day length affects the transcription of lentil AGPase isoforms differentially in stems and leaves most likely to supply carbon from the stem to other tissues to regulate carbon metabolism under short-day conditions.


Introduction of a computer-based method for automated planning of reduction paths under consideration of simulated muscular forces.
Reduction is a crucial step in the surgical treatment of bone fractures. Finding an optimal path for restoring anatomical alignment is considered technically demanding because collisions as well as high forces caused by surrounding soft tissues can avoid desired reduction movements. The repetition of reduction movements leads to a trial-and-error process which causes a prolonged duration of surgery. By planning an appropriate reduction path-an optimal sequence of target-directed movements-these problems should be overcome. For this purpose, a computer-based method has been developed. Using the example of simple femoral shaft fractures, 3D models are generated out of CT images. A reposition algorithm aligns both fragments by reconstructing their broken edges. According to the criteria of a deduced planning strategy, a modified A*-algorithm searches collision-free route of minimal force from the dislocated into the computed target position. Muscular forces are considered using a musculoskeletal reduction model (OpenSim model), and bone collisions are detected by an appropriate method. Five femoral SYNBONE models were broken into different fracture classification types and were automatically reduced from ten randomly selected displaced positions. Highest mean translational and rotational error for achieving target alignment is [Formula: see text] and [Formula: see text]. Mean value and standard deviation of occurring forces are [Formula: see text] for M. tensor fasciae latae and [Formula: see text] for M. semitendinosus over all trials. These pathways are precise, collision-free, required forces are minimized, and thus regarded as optimal paths. A novel method for planning reduction paths under consideration of collisions and muscular forces is introduced. The results deliver additional knowledge for an appropriate tactical reduction procedure and can provide a basis for further navigated or robotic-assisted developments.


βIII spectrin controls the planarity of Purkinje cell dendrites by modulating perpendicular axon-dendrite interactions.
The mechanism underlying the geometrical patterning of axon and dendrite wiring remains elusive, despite its crucial importance in the formation of functional neural circuits. The cerebellar Purkinje cell (PC) arborizes a typical planar dendrite, which forms an orthogonal network with granule cell (GC) axons. By using electrospun nanofiber substrates, we reproduce the perpendicular contacts between PC dendrites and GC axons in culture. In the model system, PC dendrites show a preference to grow perpendicularly to aligned GC axons, which presumably contribute to the planar dendrite arborization in vivo We show that βIII spectrin, a causal protein for spinocerebellar ataxia type 5, is required for the biased growth of dendrites. βIII spectrin deficiency causes actin mislocalization and excessive microtubule invasion in dendritic protrusions, resulting in abnormally oriented branch formation. Furthermore, disease-associated mutations affect the ability of βIII spectrin to control dendrite orientation. These data indicate that βIII spectrin organizes the mouse dendritic cytoskeleton and thereby regulates the oriented growth of dendrites with respect to the afferent axons.


Distribution Characteristics of Rare Earth Elements and Selenium in Hair of Centenarians Living in China Longevity Region.
In order to explore the characteristics of the rare earth elements (REEs) and selenium (Se) among the Chinese centenarians, the concentrations of REE and Se were detected in the hair of healthy centenarians living in typical Chinese longevity region, and the influences of physiological conditions and behavior on the concentrations of REE and Se were assessed. The average values of light RE (LRE) and heavy RE (HRE) are 31.87 and 11.12 ng/g. Female centenarians had higher concentrations of lanthanum (La), praseodymium (Pr), gadolinium (Gd), terbium (Tb), erbium (Er), thulium (Tm), yttrium (Y), and Se but lower levels of cerium (Ce), neodymium (Nd), samarium (Sm), europium (Eu), dysprosium (Dy), holmium (Ho), ytterbium (Yb), and lutetium (Lu). Except for Ce, the higher the age, the lower the REE and Se content were. Smoking was positively associated with Dy, Er, and Yb levels, whereas drinking habits showed no significant effect on all the elements. Elderly individuals who ate smoked and pickled food and who consumed high amounts of salt had higher levels of REE and Se in their hair, and centenarians who consumed egg and milk had higher Se and REE in the hair than did the non-eaters. This comprehensive study on the REE and Se concentrations among the healthy centenarians can provide scientific support for shaping a healthy aging society.


Regulation of neurexin 1beta tertiary structure and ligand binding through alternative splicing.
Neurexins and neuroligins play an essential role in synapse function, and their alterations are linked to autistic spectrum disorder. Interactions between neurexins and neuroligins regulate inhibitory and excitatory synaptogenesis in vitro through a "splice-insert signaling code." In particular, neurexin 1beta carrying an alternative splice insert at site SS#4 interacts with neuroligin 2 (found predominantly at inhibitory synapses) but much less so with other neuroligins (those carrying an insert at site B and prevalent at excitatory synapses). The structure of neurexin 1beta+SS#4 reveals dramatic rearrangements to the "hypervariable surface," the binding site for neuroligins. The splice insert protrudes as a long helix into space, triggers conversion of loop beta10-beta11 into a helix rearranging the binding site for neuroligins, and rearranges the Ca(2+)-binding site required for ligand binding, increasing its affinity. Our structures reveal the mechanism by which neurexin 1beta isoforms acquire neuroligin splice isoform selectivity.


7-Oxo-cholesterol potentiates pro-inflammatory signaling in human M1 and M2 macrophages.
Macrophages, the major cellular components of atherosclerotic plaques, consist of two main subsets: the pro-inflammatory, M1 or classically activated macrophages, and the anti-inflammatory, M2 or alternatively activated macrophages. The molecular and cellular mechanisms that orchestrate the macrophage polarization and activation that may play a role in plaque progression and stability are poorly understood. Recent studies suggest that oxysterols, oxidative stress-mediated cholesterol oxidation products that are abundant in atherosclerotic lesions, may affect macrophage biology. We investigated whether 7-oxo-cholesterol (7oxo-C) affected polarized human M1 and M2 macrophage phenotypes and functions. Monocyte-derived M1 and M2 macrophages were challenged with 7oxo-C and their phenotype analyzed using flow cytometric analysis, and their function via secretome profiling, the presence of endocytosis and matrix metalloproteinase-9 (MMP-9) release. 7oxo-C increased the expression of HLA-DR in M1 macrophages, and CD14 on M2 macrophages. The oxysterol also reduced CD16 expression on M1 macrophages, while reducing their endocytotic capability and increasing MMP-9 secretion in M2 macrophages. Secretome profiling from cultured cell supernatants showed that 7oxo-C stimulated the production of key pro-atherogenic mediators involved in pro-inflammatory, pro-invasive and pro-angiogenic mechanisms both in M1 and M2 cells. Hypoxic conditions potentiated the effects of 7oxo-C on M1 and M2 cells. The ability of 7oxo-C to polarize macrophages toward a pro-inflammatory state represents a potentially novel mechanism by which oxidative stress can contribute to atherosclerotic lesion progression.


Detection of nonauthorized genetically modified organisms using differential quantitative polymerase chain reaction: application to 35S in maize.
Detection of nonauthorized genetically modified organisms (GMOs) has always presented an analytical challenge because the complete sequence data needed to detect them are generally unavailable although sequence similarity to known GMOs can be expected. A new approach, differential quantitative polymerase chain reaction (PCR), for detection of nonauthorized GMOs is presented here. This method is based on the presence of several common elements (e.g., promoter, genes of interest) in different GMOs. A statistical model was developed to study the difference between the number of molecules of such a common sequence and the number of molecules identifying the approved GMO (as determined by border-fragment-based PCR) and the donor organism of the common sequence. When this difference differs statistically from zero, the presence of a nonauthorized GMO can be inferred. The interest and scope of such an approach were tested on a case study of different proportions of genetically modified maize events, with the P35S promoter as the Cauliflower Mosaic Virus common sequence. The presence of a nonauthorized GMO was successfully detected in the mixtures analyzed and in the presence of (donor organism of P35S promoter). This method could be easily transposed to other common GMO sequences and other species and is applicable to other detection areas such as microbiology.


Radiosurgery for brain metastasis: impact of CTV on local control.
The purpose of the present analysis was to assess whether adding a 1 mm margin to the gross tumour volume (GTV) improves the control rate of brain metastasis treated with radiosurgery (RS). All the patients had one or two brain metastases, 30 mm or less in diameter, and only one isocentre was used for RS. There were 23 females and 38 males. The median age was 54 years (34-76). The median Karnofsky performance status was 80 (60-100). At the time of RS, 23 patients had no evidence of extracranial disease and 38 had a progressive systemic disease. Thirty-eight patients were treated up-front with only RS. Twenty-three patients were treated for relapse or progression more than 2 months after whole brain radiotherapy. From January 1994 to July 1995, clinical target volume (CTV) was equal to GTV without any margin (33 metastases). From August 1995 to August 2000, CTV was defined as GTV plus a 1 mm margin (45 metastases). A dose of 20Gy was prescribed to the isocentre and 14Gy at the margin of CTV. The median follow-up was 10.5 months (1-45). The mean minimum dose delivered to GTV was 14.6Gy in the group without a margin and 16.8Gy in the group with a 1 mm margin (P<0.0001). The response of 11 metastases was never assessed because patients died before the first follow-up. Ten metastases recurred, eight in the group treated without a margin and two in the group treated with a 1 mm margin (P=0.01). Two-year local control rates were 50.7+/-12.7% and 89.7+/-7.4% (P=0.008), respectively. Univariate analysis showed that the treatment group (P=0.008) and the tumour volume (P=0.009) were prognostic factors for local control. In multivariate analysis, only the treatment group with a 1 mm margin was an independent prognostic factor for local control (P=0.04, RR: 5.8, 95% CI [1.08-31.13]). There were no significant differences, either in overall survival rate or in early and late side effects, between the two groups. Adding a 1 mm margin to the GTV in patients treated with RS significantly improves the probability of metastasis control without increasing the side effects.


Clinical significance of CD133 and Nestin in astrocytic tumor: The correlation with pathological grade and survival.
We aimed to investigate the interaction between CD133 and Nestin and further assessed the correlation of CD133 and Nestin with clinicopathological characteristics and survival in patients with astrocytic tumor. Totally 127 patients with astrocytic tumor underwent surgical resection were enrolled. Patients' age, gender, and World Health Organization (WHO) grade were recorded, and the survival data were extracted from the follow-up records. The expressions of CD133 and Nestin in astrocytic tumor tissues were analyzed by immunohistochemistry assay. The WHO grade I and II astrocytic tumors were defined as low-grade astrocytic tumors (LGA), the WHO grade III and IV astrocytic tumors were defined as high-grade astrocytic tumors (HGA). There were 79 (62.2%), 34 (26.8%), 14 (11.0%), and 0 (0.0%) patients with CD133 negative, low, moderate, and high expression, respectively; 7 (5.5%), 47 (37.0%), 20 (15.7%), 53 (41.7%) patients with Nestin negative, low, moderate, high expression, respectively. CD133 and Nestin were both correlated with advanced WHO grade but not with age or gender, and positive correlation was observed between CD133 and Nestin. For survival, both CD133 and Nestin were correlated with unfavorable overall survival (OS), and further analysis illustrated that Nestin but not CD133 independently predicted poor OS. Subgroup analysis also revealed that Nestin but not CD133 negatively associated with shorter OS in LGA patients, while both CD133 and Nestin were correlated with poor OS in HGA patients. CD133 and Nestin present as potential biomarkers for advanced pathological grade and poor survival in patients with astrocytic tumor.


Perioperative outcomes of major hepatic resections under low central venous pressure anesthesia: blood loss, blood transfusion, and the risk of postoperative renal dysfunction.
We have previously demonstrated that maintenance of a low central venous pressure (LCVP) combined with extrahepatic control of venous outflow reduced the overall blood loss during major hepatic resections. This study examined the overall outcomes and, in particular, renal morbidity associated with a large series of consecutive major liver resections performed with this approach. In addition, the rationale for the anesthetic management to maintain LCVP was carefully reviewed. All major hepatectomies performed between December 1991 and April 1997 were reviewed. The prospective Hepatobiliary Surgical Service database was merged with the Memorial Hospital Laboratory and Blood Bank databases to yield the nature of the operation, blood loss, blood product transfusions, outcomes, and levels of preoperative, postoperative, and discharge serum creatinine and blood urea nitrogen. A total of 496 LCVP-assisted major liver resections were performed, with no intraoperative deaths and an in-hospital mortality rate of 3.8%. The median blood loss was 645 mL. Sixty-seven percent of the patients did not require perioperative blood transfusion during surgery and the immediate 12 hours after surgery. The median number of blood transfusions was 2. Only 3% of the patients experienced a persistent and clinically significant increase in serum creatinine possibly attributable to the anesthetic technique. Renal failure directly attributable to the anesthetic technique did not occur. Major resection with LCVP allowed easy control of the hepatic veins before and during parenchymal transection. The anesthetic technique, designed to maintain LCVP during the critical stages of hepatic resection, not only helped to minimize blood loss and mortality but also preserved renal function.


Healthcare utilization and symptom variation among veterans using Behavioral Telehealth Center services.
Substance use and mental health problems are often underdiagnosed and undertreated in primary care. Veterans affairs facilities are using the Behavioral Telehealth Center (BTC) to provide evidence-based assessments for primary care patients via telephone. Whether participation in BTC services is associated with (1) increases in healthcare utilization and (2) decreases in symptoms based on behavioral health screening instruments, post-BTC services compared with pre-BTC services were investigated. Retrospective data were extracted for 1,820 patients who were referred to the BTC. Differences in utilization rates and symptom scores pre- and post-BTC services were tested using repeated measures analysis of covariance while controlling for relevant sociodemographic variables. Participants (1) utilized significantly more substance use and mental health treatment services and (2) had significantly lower alcohol and depression screening scores post-BTC services compared with pre-BTC services. This initial evaluation provides support that BTC services are associated with increased healthcare utilization and decreased alcohol and depressive symptoms.


Comparison of histopathological and flow cytometric parameters in prediction of prognosis in gastric cancer.
Flow cytometric analysis was performed retrospectively on material from 76 patients having potentially curative resection for gastric carcinoma between 1968 and 1984. The prognostic significance of DNA aneuploidy was compared with that of conventional histological grading and staging of the tumour. The presence of DNA aneuploidy was associated with a significantly poorer prognosis when compared with diploid tumours (P less than 0.02), but was not found to be predictive of survival when the presence of lymph node metastases (P less than 0.0001) and resection margin involvement (P less than 0.003) were allowed for using multiple regression analysis. When intestinal and diffuse types of gastric carcinoma were analysed separately, DNA aneuploidy was associated with a significantly shorter survival only in patients with intestinal type tumours.


Topically applied mesoridazine exhibits the strongest cutaneous analgesia and minimized skin disruption among tricyclic antidepressants: The skin absorption assessment.
Tricyclic antidepressants (TCAs) are found to have an analgesic action for relieving cutaneous pain associated with neuropathies. The aim of this study was to assess cutaneous absorption and analgesia of topically applied TCAs. Percutaneous delivery was investigated using nude mouse and pig skin models at both infinite and saturated doses. We evaluated the cutaneous analgesia in nude mice using the pinprick scores. Among five antidepressants tested in the in vitro experiment, mesoridazine, promazine and doxepin showed a superior total absorption percentage. The drug with the lowest total absorption percentage was found to be fluphenazine (<7%) either at an infinite dose or at saturated solubility. The follicular pathway was important for mesoridazine and promazine delivery. Mesoridazine showed stronger skin analgesia than the other TCAs although the in vivo skin absorption of mesoridazine (0.34nmol/mg) was less than that of promazine (0.80nmol/mg) and doxepin (0.74nmol/mg). Mesoridazine had a prolonged duration of pain relief (165min) compared to promazine (83min) and doxepin (17min). The skin irritation test demonstrated an evident barrier function deterioration and cutaneous erythema by promazine and doxepin treatment, whereas mesoridazine caused no obvious adverse effect by topical application for up to 7days.


An outbreak of non-A, non-B hepatitis associated with the infusion of a commercial factor IX complex during cardiovascular surgery.
An outbreak of non-A, non-B hepatitis was recognized among cardiovascular surgical patients from one hospital in June 1985. Illness was found to be significantly associated with a commercial brand of factor IX complex given to patients because of intraoperative bleeding. A change in the commercial brand of factor IX stocked by the hospital pharmacy had occurred in October 1984 and coincided with the onset of the outbreak. A retrospective study of cardiovascular surgery patients identified 23 cases and 7 probable cases of non-A, non-B hepatitis among patients who had received infusions of brands A and B factor IX complex. Three cases were in brand A recipients and 27 were in brand B recipients. Respective brand-specific attack rates were 5 and 42% (relative risk = 7.7; p less than 2 x 10(-5); chi 2 test). Nineteen of 30 case patients (63%) were jaundiced, including 2 brand A recipients and 17 brand B recipients. Median peak serum aminotransferase was 690.5 IU (range 27-2,824). The incubation period for cases in brand B recipients was a median of 7 weeks (range 2-17 weeks). Prevention of non-A, non-B hepatitis in this population requires adhering to strict indications for the use of clotting factor preparations and avoiding these products when at all possible. Heat treatment of clotting factor products may reduce the risk of viral disease transmission, but certain methods may not inactivate the causative agents of non-A, non-B hepatitis.


Optimal quantum network decongestion strategies.
This study clarifies the problem of decongestion in quantum networks, with a specific focus on the crucial task of entanglement distribution. Entangled particles are a valuable resource in quantum networks, as they are used for most quantum protocols. As such, ensuring that nodes in quantum networks are supplied with entanglement efficiently is mandatory. Many times, parts of a quantum network are contested by multiple entanglement resupply processes and the distribution of entanglement becomes a challenge. The most common network intersection topology, the star-shape and it's various generalizations, are analyzed, and effective decongestion strategies, in order to achieve optimal entanglement distribution, are proposed. The analysis is comprehensive and relies on rigorous mathematical calculations which aids in selecting the most appropriate strategy for different scenarios optimally.


Differential gene expression profiles in colon epithelium of two rat strains with distinct susceptibility to colon carcinogenesis after exposure to PhIP in combination with dietary high fat.
Colon cancers develop through accumulation of multiple genetic and epigenetic alterations in colon epithelial cells, and the environment of the genetically altered epithelial cells may also have a substantial impact on their further development to cancer. In the present study, groups of 6-week-old F344 and ACI male rats, the former strain being susceptible to colon carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and the latter being relatively resistant, were subjected to a long-term carcinogenesis experiment using our intermittent feeding protocol of PhIP in combination with a high-fat diet, which serves as a relevant risk factor that promotes the development of colon cancers. Animals were sacrificed at 60 weeks, and global gene expression analyses of normal parts of colon epithelial tissues were conducted using a high-density oligonucleotide microarray to elucidate the differential gene expression profile (environment) in normal colonic regions between F344 and ACI strains. Of 8799 entries on the RatU34A array, 74 genes exhibited 3-fold or greater variation. A subset of genes encoding ribosomal RNAs and proteins were highly preferentially expressed in the F344 strain. In addition, genes encoding fatty acid binding proteins and the peroxisome membrane protein 70 appeared up-regulated in the susceptible F344 strain. In the ACI strain, a mismatch repair gene, Msh2, was preferentially expressed, at approximately 20-fold the F344 level, along with a gene encoding a detoxification enzyme, catechol-O-methyltransferase. The combined effects of the repertoire of these differentially expressed genes in normal colon epithelial tissues may account for the distinct susceptibilities of F344 and ACI strains to colon carcinogenesis.


Saponin-based adjuvant-induced dendritic cell cross-presentation is dependent on PERK activation.
Saponin-based adjuvants (SBAs) are promising new adjuvants that stand out as they not only enforce CD4 + T cell-mediated immunity and antibody responses, but also induce an unprecedented level of antigen cross-presentation by dendritic cells (DC) and subsequent CD8 + T cell activation. We discovered that SBA's ability to boost cross-presentation depends on the induction of lipid bodies (LBs). Moreover, the MHCIIloCD11bhi DC subset was identified to be most responsive to SBA-induced cross-presentation. The aim is to further unravel the mechanisms behind the induction of DC cross-presentation by SBAs. Here we show that SBAs specifically induce the PKR-like Endoplasmic Reticulum kinase (PERK) pathway and that SBA-induced DC cross-presentation is dependent on activation of the PERK pathway. PERK activation and LB formation are both crucial for SBA-induced cross-presentation and PERK inhibition has little or no effect on SBA-induced LB formation. SBA's responsiveness, LB formation and PERK activation are specific for the MHCIIloCD11bhi DCs. These findings contribute to understanding the pathways involved in SBA-induced cross-presentation and immune activation which will ultimately lead to the development of vaccines with improved efficiency and safety.


DNA versus RNA oxidation in Parkinson's disease: Which is more important?
8-hydroxy-2 deoxyguanosine (8-OHdG) and the 8-hydroxyguanosine (8-OHG) are the most widely used biomarkers of nucleoside oxidation affecting DNA and RNA and are considered reliable markers of oxidative stress. Increased levels of these markers are found in the various biological fluids of patients with neurodegenerative disorders. The primary aim of our study was to assess the differences of investigated markers between patient groups and subsequently study the influence of clinical factors that might modify the levels of investigated markers during the disease progression. In this study, we analysed the 8-OHdG and 8-OHG levels in the cerebrospinal fluid (CSF) and serum from 44 patients with Parkinson's disease (PD) and 32 controls using an ELISA. There were significantly higher CSF levels of both investigated markers in Parkinson's disease patients as compared to controls (p=0.02 and p=0.04). Significantly higher CSF values of 8-OHdG were found in PD patients without dementia (p=0.05), whereas patients with dementia recorded lower 8-OHG CSF levels compared to controls (p=0.04). The disease duration and age influenced the levels of both markers within investigated groups. Oxidative DNA damage plays an important role in the early stages of PD, whereas during the progression of the disease the process is more complex, and other mechanisms are in the foreground. The measurement of 8-OHdG might be used as an "early-stage marker", whereas the decrease of 8-OHG in CSF might reflect the degree of neurodegeneration during the disease progression, suggesting its utility as a prognostic marker of advanced PD stages.


Bone marrow aspirate: a diagnostic tool for primary hyperoxaluria type 1.
Type1 primary hyperoxaluria is an infrequent autosomal recessive metabolic disease characterized by the accumulation of calcium oxalate in the kidney, which leads to end stage renal disease. In fact, the diagnosis of this disease is mandatory in order to avoid graft loss. To assess the incidence of primary hyperoxaluria and to develop the diagnostic value of bone marrow infiltration by calcium oxalate in uremic stone former patients. This study was conducted on a cohort of stone former patients identified in the south of Tunisia over a period of 18 years. Baseline characteristics were recorded. Clinical and laboratory data were collected on chart review. Secondary forms of hyperoxaluria were excluded. Bone marrow aspirate was performed in uremic patients from this cohort because early hyperoxaluria was suspected. Diagnostic accuracy of this test relating to sensitivity, specificity, positive predictive value and negative predictive value were also calculated. A cohort of 31 patients comprising 17 male patients and 14 female patients were identified. During this time of diagnosis, the patient's ages ranged from 9 to 57 years old and 22 of them (70%) unfortunately died. Bone marrow aspirate was safely done in 16 uremic patients. It was positive in 12 patients and negative in 4 patients. Sensitivity, specificity, positive predictive value and negative predictive value were respectively 85%, 100%, 100% and 50%. The bone marrow examination represents both an easy and a worldwide feasible solution for the diagnosis of oxalosis, which affords an early diagnosis.


[Complete androgen insensitivity syndrome: a novel mutation in a Tunisian family].
Complete androgen insensitivity is a rare syndrome. It is caused by a mutation in the androgen receptor gene. We describe a novel mutation in exon 1. We report the case of a 29 year-old girl with complete androgen insensitivity syndrome discovered during the exploration of a primary amenorrhoea. The family investigation revealed two other cases. The diagnosis was oriented by the clinical and the biological features and confirmed by the molecular study. A new mutation of the androgen receptor gene, as a deletion in exon 1 not described previously, was identified. Through these cases, clinical, hormonal and histological particularities were analysed.


The Effects of Long-term, Low-dose β-N-methylamino-L-alanine (BMAA) Exposures in Adult SODG93R Transgenic Zebrafish.
β-N-Methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria, which has been implicated in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). It is postulated that chronic exposure to BMAA can lead to formation of protein aggregates, oxidative stress, and/or excitotoxicity, which are mechanisms involved in the etiology of ALS. While specific genetic mutations are identified in some instances of ALS, it is likely that a combination of genetic and environmental factors, such as exposure to the neurotoxin BMAA, contributes to disease. We used a transgenic zebrafish with an ALS-associated mutation, compared with wild-type fish to explore the potential neurotoxic effects of BMAA through chronic long-term exposures. While our results revealed low concentrations of BMAA in the brains of exposed fish, we found no evidence of decreased swim performance or behavioral differences that might be reflective of neurodegenerative disease. Further research is needed to determine if chronic BMAA exposure in adult zebrafish is a suitable model to study neurodegenerative disease initiation and/or progression.


Long-Term Stability of a 13.7 × 30.5-m (45 × 100-ft) Undercut Span Beneath Cemented Rockfill at the Turquoise Ridge Mine, Nevada.
In 2001, researchers from the National Institute for Occupational Safety and Health (NIOSH) installed instruments at the Turquoise Ridge Mine in cooperation with Placer Dome, Inc. to monitor the geomechanical behavior and stability of a cemented rockfill (CRF) sill and the surrounding host rock during test mining of a large undercut span beneath backfill. Six parallel, adjacent drifts were mined and backfilled to construct a CRF sill, approximately 22.9 m (75 ft) wide by 30.5 m (100 ft) long. The sill was then partially undercut, successfully creating a 13.7-m (45-ft) wide by 30.5-m (100-ft) long span beneath the CRF. Only small vertical displacements were measured in the overlying host rock during mining, with most of the movement occurring at shallow depths in the mine roof. Because the back above the CRF sill remained stable, the majority of the mining-induced stress was transferred to the host rock abutments rather than to the backfilled drifts. During retreat mining of the undercut span, the CRF sill and the mine roof remained stable. Most of the measured vertical displacement was caused by separation of the backfill from the overlying host rock, or deflection of the CRF sill, which was comparable to the deflection of a monolithic, elastic plate having similar dimensions, material properties, and undercut spans. The CRF sill moved in mass as a single unit rather than as individual drift segments, and the vertical cold joints between adjacent backfill drifts did not adversely affect their stability. Additional measurements collected from the instruments have shown that the backfill span is still intact and in stable condition more than 16 years after the completion of undercut mining. Displacements in the mine roof and abutments have stabilized, and vertical stress and deformation within the CRF have generally leveled off or decreased. Although only slight mining-induced loads were transferred to the backfilled drifts, the CRF has confined the abutment ribs and mine roof, thereby improving their long-term stability. Results of compressive and tensile strength tests conducted with CRF samples from the test site indicate that the long-term compressive strength gain for CRF is similar to that of concrete, and that the tensile-to-compressive strength ratio for CRF is about 1/6 rather than 1/10. Assuming the in-place CRF gained strength at the same rate as the lab samples, an analytical analysis of the flexural stability of the CRF undercut span shows that the Factor of Safety for the span should have logically increased over time. By providing a better understanding of the long-term strength properties and geomechanical behavior of CRF, these research findings help improve the methods that are used for designing stable, long-term undercut entries beneath cemented backfill.


Research advances of microbial enhanced oil recovery.
Microbial enhanced oil recovery (MEOR), characterized with the virtues of low cost and environmental protection, reflects the prevalent belief in environmental protection, and is attracting the attention of more researchers. Nonetheless, with the prolonged slump in global oil prices, how to further reduce the cost of MEOR has become a key factor in its development. This paper described the recent development of MEOR technology in terms of mechanisms, mathematical models, and field application, meanwhile the novel technologies of MEOR such as genetically engineered microbial enhanced oil recovery (GEMEOR) and enzyme enhanced oil recovery (EEOR) were introduced. The paper proposed three possible methods to decrease the cost of MEOR: using inexpensive nutrients as substrates, applying a mixture of chemical and biological agents, and utilizing crude microbial products. Additionally, in order to reduce the uncertainty in the practical application of MEOR technology, it is essential to refine the reservoir screening criteria and establish a sound mathematical model of MEOR. Eventually, the paper proposes to combine genetic engineering technology and microbial hybrid culture technology to build a microbial consortium with excellent oil displacement efficiency and better environmental adaptability. This may be a vital part of the future research on MEOR technology, which will play a major role in improving its economic efficiency and practicality.


Preoperative serum sex hormone-binding globulin as a predictive marker for extraprostatic extension of tumor in patients with clinically localized prostate cancer.
We investigated the relationships of serum sex hormone-binding globulin (SHBG) level with known prognostic factors for prostate cancer in men who received radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. Preoperative serum levels of SHBG were analyzed in 288 consecutive patients who were scheduled to undergo RRP for clinically localized prostate cancer. We investigated the potential associations of preoperative serum SHBG level with various clinical and pathological factors. Accuracy of variables in predicting adverse pathological features was assessed via receiver operator characteristics (ROC) curves. In univariate analysis, preoperative serum SHBG level was observed to be significantly associated with extraprostatic extension of a tumor (p=0.019) and with pathological Gleason score (p=0.001). In multivariate analysis, serum SHBG level (p=0.039) along with serum PSA (p<0.001) level, biopsy Gleason score (p<0.001), and clinical stage (p=0.004) was observed to be an independent predictor of the extraprostatic extension of prostate cancer. The area under ROC curve that demonstrated the performance of a multivariate logistic regression model (MLRM), which included serum SHBG level and other preoperative variables, in predicting extraprostatic extension of tumor was larger than that of MLRM without SHBG (0.797 vs. 0.758, p=0.121). Meanwhile, serum SHBG level was not observed to be significantly associated with pathological Gleason score in multivariate analysis (p=0.303). Our data showed that serum SHBG level is an independent predictive factor for extraprostatic extension of tumor in patients with clinically localized prostate cancer.


Mobility of photosynthetic proteins.
The mobility of photosynthetic proteins represents an important factor that affects light-energy conversion in photosynthesis. The specific feature of photosynthetic proteins mobility can be currently measured in vivo using advanced microscopic methods, such as fluorescence recovery after photobleaching which allows the direct observation of photosynthetic proteins mobility on a single cell level. The heterogeneous organization of thylakoid membrane proteins results in heterogeneity in protein mobility. The thylakoid membrane contains both, protein-crowded compartments with immobile proteins and fluid areas (less crowded by proteins), allowing restricted diffusion of proteins. This heterogeneity represents an optimal balance as protein crowding is necessary for efficient light-energy conversion, and protein mobility plays an important role in the regulation of photosynthesis. The mobility is required for an optimal light-harvesting process (e.g., during state transitions), and also for transport of proteins during their synthesis or repair. Protein crowding is then a key limiting factor of thylakoid membrane protein mobility; the less thylakoid membranes are crowded by proteins, the higher protein mobility is observed. Mobility of photosynthetic proteins outside the thylakoid membrane (lumen and stroma/cytosol) is less understood. Cyanobacterial phycobilisomes attached to the stromal side of the thylakoid can move relatively fast. Therefore, it seems that stroma with their active enzymes of the Calvin-Benson cycle, are a more fluid compartment in comparison to the rather rigid thylakoid lumen. In conclusion, photosynthetic protein diffusion is generally slower in comparison to similarly sized proteins from other eukaryotic membranes or organelles. Mobility of photosynthetic proteins resembles restricted protein diffusion in bacteria, and has been rationalized by high protein crowding similar to that of thylakoids.


Bortezomib induces HSV-1 lethality in mice with neutrophil deficiency.
Bortezomib suppressing NF-κB activity is an effective therapy for patients with myeloma or lymphoma. However, this drug can cause adverse effects, neutropenia, and recurrent infections of herpes viruses. Among herpes viruses, HSV-1 can reactivate to induce mortality. The important issues regarding how bortezomib diminishes neutrophils, whether bortezomib can induce HSV-1 reactivation, and how bortezomib exacerbates HSV-1 infection, need investigation. Using the murine model, we found that bortezomib induced HSV-1 reactivation. Bortezomib diminished neutrophil numbers in organs of uninfected and HSV-1-infected mice and turned a nonlethal infection to lethal with elevated tissue viral loads. In vitro results showed that bortezomib and HSV-1 collaborated to enhance the death and apoptosis of mouse neutrophils. The leukocyte deficiency induced by chemotherapies is generally believed to be the cause for aggravating virus infections. Here we show the potential of pathogen to exacerbate chemotherapy-induced leukocyte deficiency.


In vitro affinity maturation to improve the efficacy of a hypoxia-inducible factor 1α single-domain intrabody.
Affinity is an important property of therapeutic antibodies, so improving affinity is critical to the biological activity and clinical efficacy. An anti-HIF-1α nanobody, VHH212, was screened via a native ribosome display library with a 26.6 nM of KD value was used as the parent. In this paper, a Venn-intersection of multi-algorithms screening (VIMAS) strategy for computer-aided binding affinity prediction was designed. Homology modeling and protein docking methods were used to substitute the need for a crystal structure. Finally, a mutant with a 17.5-fold enhancement in binding affinity (1.52 nM) was obtained by using the VIMAS strategy. Furthermore, the biological activity of mutants was verified at the cellular level. Targeting HIF-1α can sensitize PDAC (pancreatic ductal adenocarcinoma) tumors to gemcitabine, which is a potential co-treatment method for pancreatic cancer patients. Our results showed that the cytotoxicity of gemcitabine on pancreatic cancer cell lines increased with the enhanced-affinity of an intrabody under combined treatment.


Augmentation of neovascularization in murine hindlimb ischemia by combined therapy with simvastatin and bone marrow-derived mesenchymal stem cells transplantation.
We postulated that combining high-dose simvastatin with bone marrow derived-mesenchymal stem cells (MSCs) delivery may give better prognosis in a mouse hindlimb ischemia model. Mouse hindlimb ischemia model was established by ligating the right femoral artery. Animals were grouped (n = 10) to receive local injection of saline without cells (control and simvastatin groups) or with 5 × 106 MSCs (MSCs group). Animals received either simvastatin (20 mg/kg/d, simvastatin and combination groups) or saline(control and MSCs group) gavages for continual 21 days. The blood flow was assessed by laser Doppler imaging at day 0,10 and 21 after surgery, respectively. Ischemic muscle was harvested for immunohistological assessments and for VEGF protein detection using western blot assay at 21 days post-surgery. In vitro, MSCs viability was measured by MTT and flow cytometry following culture in serum-free medium for 24 h with or without simvastatin. Release of VEGF by MSCs incubated with different doses of simvastatin was assayed using ELISA. Combined treatment with simvastatin and MSCs induced a significant improvement in blood reperfusion, a notable increase in capillary density, a highest level of VEGF protein and a significant decrease in muscle cell apoptosis compared with other groups. In vitro, simvastatin inhibited MSCs apoptosis and increased VEGF release by MSCs. Combination therapy with high-dose simvastatin and bone marrow-derived MSCs would augment functional neovascularization in a mouse model of hindlimb ischemia.


Regulation of antilipopolysaccharide factors, ALFPm3 and ALFPm6, in Penaeus monodon.
ALFPm6, a member of antimicrobial peptide in the antilipopolysaccharide factor (ALF) family from Penaeus monodon, plays important roles in shrimp immunity against pathogens. However, its antimicrobial activity and underlying mechanism have not been reported. The synthetic cyclic ALFPm6#29-52 peptide (cALFPm6#29-52) corresponding to the ALFPm6 LPS-binding domain can agglutinate and exhibited bacterial killing activity toward a Gram-negative bacterium, Escherichia coli 363 and Gram-positive bacteria, Bacillus megaterium, Aerococcus viridans, and Micrococcus luteus, with MIC values of 25-50 μM. Specifically, ALFPm6 and ALFPm3, the most abundant ALF isoforms, are different in terms of gene expression patterns upon pathogen infections. Herein, the regulation of ALFPm3 and ALFPm6 gene expression was studied. The 5'-upstream and promoter sequences were identified and the putative transcription factor (TF)-binding sites were predicted. The narrow down assay indicated that the ALFPm3 promoter and partial promoter of the ALFPm6 active regions were located at nucleotide positions (-814/+302) and (-282/+85), respectively. Mutagenesis of selected TF-binding sites revealed that Rel/NF-κB (-280/-270) of ALFPm3 and C/EBPβ (-88/-78) and Sp1 (-249/-238) sites of ALFPm6 were the activator-binding sites. Knockdown of the PmMyD88 and PmRelish genes in V. harveyi-infected shrimp suggested that the ALFPm3 gene was regulated by Toll and IMD pathways, while the ALFPm6 gene was regulated by the Toll pathway.


Optimistic bias: the more you do, the better you think it goes. Survey analysis of reverse shoulder arthroplasty.
Even though heuristics are very helpful, several biases have been described related to their use. The aim of this study is to analyze the influence of surgery volume on the surgeon's perception of pain improvement in patients after having received a reverse total shoulder arthroplasty. Successive independent samples study. Shoulder surgeons attending four shoulder meetings. 149 Shoulder surgeons were included. Physicians were asked to postulate the preoperative and postoperative pain of patients receiving a reverse shoulder arthroplasty and respond by putting a mark on two visual pain scales. Pain improvement, years of shoulder practice, number of shoulder studies read over 6 months and the number of reverse shoulder arthroplasties performed per year. To compare the answers of the survey-study, a cohort of 95 patients who had undergone reverse shoulder Arthroplasty because of a rotator cuff arthropathy were prospectively followed. Regarding the pain score before and after surgery, the patient cohort showed a mean improvement of 6.84 points. In terms of the doctors, the more years of surgical practice, led them to have a greater expectation of improvement (p=0.004). Moreover, the greater the number of prostheses they implanted, the greater the expectation of improvement (p=0.0005). It was the same in terms of the number of studies read by them (p=0.001). Years of practice, hospital position and the number of shoulder arthroplasties done per year all favor the surgeon's perception that their patients obtain a greater pain relief after receiving a shoulder arthroplasty than the real improvement in pain relief the patients experience.


The use of operant conditioning techniques in the respiratory rehabilitation of the tetraplegic.
This paper discusses the development of a pilot project in respiratory rehabilitation as part of the total rehabilitation of the tetraplegic and high paraplegic. The principles of neuromuscular exercise and of behaviouristic psychology introduce the subject of operant learning in the rehabilitation setting. Incentive spirometry is described as the basic element in the development of a respiratory rehabilitation programme. The preliminary results are analysed and a recommendation made that such a programme materially increases the respiratory function of the tetraplegic, and, not least, assists in his ability to combat intercurrent respiratory infection.


Functional analysis of a novel male fertility CYP86MF gene in Chinese cabbage (Brassica campestris L. ssp. chinensis makino).
In our earlier work, a cytochrome P450 CYP86MF gene was isolated from floral bud of Chinese cabbage (Brassica campestris L. ssp. chinensis Makino, syn. B. rapa L.) by mRNA differential display PCR (DD-PCR) and rapid amplification of cDNA ends (RACE). To unravel the biological function of CYP86MF gene, the antisense fragment from the CYP86MF gene was transferred into Chinese cabbage pak-choi (B. campestris ssp. chinensis var. communis Tsen et Lee). Out of 22 plants transformed with the antisense gene constructed from the CYP86MF, 20 reached to flowering stage. Morphological investigations showed that the transgenic plants developed the normal floral organ. However, they remained self-infertile, even when artificial self-pollination was performed in the bud stage. Pollen germination test indicated that the pollen from the transgenic line TB-2 could not germinate normally. Further physiological, biochemical and cytological analyses showed that only significant difference was detectable in contents of the endogenous hormones, and a layer of unknown material adhered to the surface of microspore. The present studies thus provided valuable clues for understanding the biological function of the CYP86C subfamily genes. Furthermore, our studies also demonstrate a novel method for obtaining artificial male sterility line of Chinese cabbage.


Differences in the placental membrane cytokine response: a possible explanation for the racial disparity in preterm birth.
The prematurity rate is higher in African-Americans (AA) compared with Caucasians (C). As spontaneous preterm labor has been hypothesized to be a host inflammatory response disease racial differences in human placental membrane inflammatory cytokine and prostaglandin pathway gene expression patterns between AA and C were examined in this report. Placental membranes (amniochorion) collected from AA and C women from cesareans at term were maintained in an organ explant system and stimulated with endotoxin (lipopolysaccharide, LPS). Microarray analysis and enzyme-linked immunosorbent assay was performed on mRNAs and culture media from AA- and C-derived membranes to document any differences in mRNA expression and protein production of IL-1, IL-6, IL-8, IL-10 and expression of cyclooxygenase 1 (COX-1), COX-2 and 15-hydroxyprostaglandin dehydrogenase (PGDH). Increased mRNA expression of IL-1, IL-8 and COX-2 in AA and IL-6, IL-10, COX-1 and PGDH in C were documented after LPS stimulation. Concentration of IL-1 was significantly higher in media derived from AA whereas IL-6 and IL-10 concentrations were higher in C with no differences observed in IL-8 after LPS stimulation compared with respective unstimulated controls. These data document ethnic diversity in placental membrane immune response.


Volatile metabolomics and chemometric study provide insight into the formation of the characteristic cultivar aroma of Hemerocallis.
Due to its ornamental, edible, and medicinal value, Hemerocallis has been historically loved and used in China. However, the current understanding of the aromatic profiles of this flower is rather limited. This work aimed to evaluate and classify the aromatic profiles of Hemerocallis flowers from 10 cultivars, the volatiles of which were analyzed using solid-phase microextraction-gas chromatography-mass spectrometry. Sensory evaluation, odor activity value and relative odor activity value calculations, and chemometric analysis were also performed, the result showed that a total of 81 volatile components were identified. Linalool, 3-furanmethanol, indole, phenylacetonitrile, nerolidol, benzaldehyde, nonanal, geranial, (E)-β-ocimene, and volatile components specific to the different types were found to have an essential role in identifying these 10 varieties. The findings presented in this thesis add to our understanding of Hemerocallis.


Genetic modelling of the PTEN/AKT pathway in cancer research.
The focus on targeted therapies has been fuelled by extensive research on molecular pathways and their role in tumorigenesis. Novel models of human cancer have been created to evaluate the role of specific genes in the different stages of cancer. Currently, mouse modelling of human cancer is possible through the expression of oncogenes, specific genetic mutations or the inactivation of tumour suppressor genes, and these models have begun to provide us with an understanding of the molecular pathways involved in tumour initiation and progression at the physiological level. Additionally, these mouse models serve as an excellent system to evaluate the efficacy of currently developed molecular targeted therapies and identify new potential targets for future therapies. The PTEN/AKT pathway is implicated in signal transduction through tyrosine kinase receptors and heterotrimeric G protein-linked receptors. Deregulation of the PTEN/AKT pathway is a common event in human cancer. Despite the abundant literature, the physiological role of each element of the pathway has begun to be uncovered thanks to genetically engineered mice. This review will summarise some of the key animal models which have helped us to understand this signalling network and its contribution to tumorigenesis.


The relationship of retinal sensitivity and rhodopsin in human infants.
During dark adaptation after full field, greater than or equal to 90% bleaches recovery of sensitivity and regeneration of rhodopsin were studied using electroretinographic and pupillographic techniques in both 10-week-old infants and adults. The courses of scotopic sensitivity recovery and rhodopsin regeneration of infants and adults were similar and were reasonably well fit by single exponentials having tau = 400 sec. For both infants and adults log scotopic sensitivity was linearly related to the proportion of rhodopsin present during dark adaptation. It is concluded that by age 10 weeks human distal retinal processes that occur after photolysis are equivalent to those of adults.


Placental form of membrane-bound neutral arylamidase found in renal cell carcinoma.
A placental form of membrane-bound neutral arylamidase was found in the tissue of renal cell carcinoma. Membrane-bound neutral arylamidases from renal cell carcinoma, an intact part of the same kidney and placenta, had the same molecular weight (240 000) and were identical with respect to KM value and effect of inhibition by chelators or amino acids. Membrane-bound neutral arylamidase from renal carcinoma had the same electrophoretic mobility and heat stability as placental membrane-bound neutral arylamidase, but differed from kidney membrane-bound neutral arylamidase with respect to electrophoretic mobility, heat stability and susceptibility to urea inactivation. Results suggest the carcinoplacental alterations in membrane-bound neutral arylamidase isoenzyme in renal cell carcinoma.


Addressing rural and remote access disparities for patients with inflammatory arthritis through video-conferencing and innovative inter-professional care models.
The aim of the present study was to evaluate whether rheumatoid arthritis (RA) patients followed longitudinally using video-conferencing and inter-professional care support have comparable disease control to those followed in traditional in-person rheumatology clinics. This was a randomized controlled trial for 85 RA patients allocated to either traditional in-person rheumatology follow-up or video-conferenced follow-up with urban-based rheumatologists and rural in-person physical therapist examiners. Follow-up was every 3 months for 9 months. Outcome measures included disease activity metrics (disease activity in 28 joints with CRP measure score [DAS28-CRP], and RA disease activity index [RADAI]), modified health assessment questionnaire (mHAQ), quality of life (EuroQOL five dimensions questionnaire [EQ5D]) and patient satisfaction (nine-item visit-specific satisfaction questionnaire [VSQ9]). Of 85 participants, 54 were randomized to the video-conferencing team model and 31 to the traditional clinic (control group). Dropout rates were high, with only 31 (57%) from the video-conferencing and 23 (74%) from the control group completing the study. The mean age for study participants was 56 years; 20% were male. Mean RA disease duration was 13.9 years. There were no significant between-group differences in DAS28-CRP, RADAI, mHAQ or EQ5D scores at baseline or over the study period. Satisfaction rates were high in both groups. We found no evidence of a difference in effectiveness between inter-professional video-conferencing and traditional rheumatology clinic for both the provision of effective follow-up care and patient satisfaction for established RA patients. High dropout rates reinforce the need for consultation with patients' needs and preferences in developing models of care. While use of video-conferencing/telehealth technologies may be a distinct advantage for some patients, there may be loss of travel-related auxiliary benefits for others.


Use of PCR primers derived from a putative transcriptional regulator gene for species-specific determination of Listeria monocytogenes.
Listeria monocytogenes is an opportunistic bacterial pathogen that has accounted for an important portion of human foodborne diseases worldwide. In this study, through comparative analysis of L. innocua and L. monocytogenes genomic sequences, we selected a L. monocytogenes specific gene (lmo0733) that has the potential for specific detection of L. monocytogenes. Using PCR primers (lmo0733F and lmo0733R) derived from this gene, a specific fragment of 453 bp was amplified only from genomic DNA of L. monocytogenes strains. PCR products from other Listeria species as well as other Gram-positive and -negative species were not detectable, confirming the specificity of this assay. Thus, the PCR test employing primers lmo0733F and lmo0733R represents an additional tool in the diagnostic arsenal for rapid, sensitive and specific detection and identification of human infections due to L. monocytogenes.


The effect of water and nitrogen amendments on photosynthesis, leaf demography, and resource-use efficiency in Larrea tridentata, a desert evergreen shrub.
In the Chihuahuan Desert of southern New Mexico, both water and nitrogen limit the primary productivity of Larrea tridentata, a xerophytic evergreen shrub. Net photosynthesis was positively correlated to leaf N, but only in plants that received supplemental water. Nutrient-use efficiency, defined as photosynthetic carbon gain per unit N invested in leaf tissue, declined with increasing leaf N. However, water-use efficiency, defined as the ratio of photosynthesis to transpiration, increased with increasing leaf N, and thus these two measures of resource-use efficiency were inversely correlated. Resorption efficiency was not significantly altered over the nutrient gradient, nor was it affected by irrigation treatments. Leaf longevity decreased significantly with fertilization although the absolute magnitude of this decrease was fairly small, in part due to a large background of insect-induced mortality. Age-specific gas exchange measurements support the hypothesis that leaf aging represents a redistribution of resources, rather than actual deterioration or declining resource-use efficiency.


Discovering metabolites of post-harvest fungicides in citrus with liquid chromatography/time-of-flight mass spectrometry and ion trap tandem mass spectrometry.
In this study, we benefit from the combination of liquid chromatography (LC)/time-of-flight (TOF) MS accurate mass measurements to generate elemental compositions of ions and LC/ion trap multiple MS (MSn) providing complementary structural information, which is useful for the elucidation of unknown organic compounds at trace levels in complex food extracts. We have applied this approach to investigate different citrus fruits extracts, and we have identified two post-harvest fungicides (imazalil and prochloraz), the main degradation product of imazalil ([M + H]+, m/z 257) and a non-previously reported prochloraz degradation product ([M + H]+, m/z 282). The database-mediated identification of the parent compounds was based on the generated elemental composition obtained from accurate mass measurements and additional qualitative information from the high resolution chlorine isotopic clusters of both the protonated molecules (imazalil, [M + H]+ 297.0556, <0.1 ppm error, 2-Cl; prochloraz, [M + H]+ 376.0381, 1.9 ppm error, 3-Cl) and their characteristic fragments ions (imazalil: m/z 255 and 159; prochloraz: m/z 308 and 266). The correlation between the structural information provided by ion trap MS/MS fragmentation pathways of the parent species and the TOF accurate mass elemental composition data of the degradation products were the key to elucidate the structures of the degradation products of both post-harvest fungicides. Finally, where standards were not available (prochloraz), further confirmation was obtained by synthesizing the proposed degradation product by acid hydrolysis of the parent standard and confirmation by LC/TOF-MS.