Reward prospect improves inhibitory control in female university students with a history of childhood sexual and physical abuse.
Childhood abuse and neglect increase the risk for psychiatric disorders (e.g., depression and anxiety) during adulthood and have been associated with deficits in cognitive control. The specific mechanisms underlying these cognitive control deficits are still unknown. This study examined the expectation for reward to improve inhibitory control in young women (ages 18-35 years) with a history of childhood sexual and/or physical abuse (AG, N = 28), childhood emotional and/or physical neglect (NG, N = 30), or unaffected comparison women (HC, N = 40). They completed a previously validated rewarded (color-word) Stroop task and filled out questionnaires on depression, anxiety, and resilience. Surprisingly, a significant group by reward interaction revealed larger performance benefits under reward prospect (relative to no-reward) for the AG group relative to both the NG and HC groups. A small sample size limiting generalizability. These results demonstrate sensitivity of abused subjects to reward in modulating cognitive control and might aid in discussing whether using reward schedules during therapeutic interventions could be effective.


Nineteen-year follow-up of the silastic double stemmed hinge prosthesis of the first metatarsophalangeal joint.
The purpose of this retrospective study is to evaluate patient-related outcome and reoperation rate of the Swanson prosthesis in patients with and without grommets. Between 1981 and 1999, 98 Swanson MTP-1 prostheses were implanted in 84 patients (14 bilateral). The average follow-up was 19 years. Patients were asked to fill in the Foot and Ankle Outcome Score (FAOS) questionnaire and were asked if they had undergone reoperations. In addition, medical records where searched. 36 patients (mean age 71 years) returned the questionnaire. All median FAOS sub scores were 100. There were no differences in FAOS sub scores between patients who had a prosthesis with or without grommets, except for FAOS "activities in daily living" which was lower for patients without grommets. Reoperation rate was 4%. The Swanson silastic double stemmed hinge prosthesis showed good to excellent patient-related outcome and reoperation rate at long-term follow-up.


Synthesis and structure-activity relationships of selective norepinephrine reuptake inhibitors (sNRI) with improved pharmaceutical characteristics.
The design synthesis and SAR of a series of chiral ring-constrained norepinephrine reuptake inhibitors with improved physicochemical properties is described. Typical compounds are potent (IC(50)s<10 nM), selective against the other monoamine transporters, weak CYP2D6 inhibitors (IC(50)s>1 microM) and stable to oxidation by human liver microsomes. In addition, the compounds exhibit a favorable polarity profile.


Dyskeratosis in human and experimental oral precancer and cancer. An immunohistochemical and ultrastructural study in men, mice and rats.
Dyskeratotic cells were examined with light and electron microscopy in human oral leukoplakias and carcinomas and in chemically-induced oral premalignant and malignant lesions of mice and rats. Specific antisera against small and large keratins were used to analyse the distribution of keratin polypeptides. In normal oral mucosa, basal cells did not react with antibodies against large keratins in contrast to the suprabasal cells which did react. Small keratins were found in all epithelial cell layers. In human and experimental premalignant and malignant lesions, intensely labelled dyskeratotic cells were seen, which contained small and large keratins regardless of their position in the epithelium. At the ultrastructural level, these cells showed dense aggregates of tonofilaments. Dyskeratotic cells were often seen in advanced stages of degeneration of phagocytosis of these cells by macrophages and giant cells was frequent. The disturbance of the keratinization process in oral precancer and cancer is easily visualized using keratin antisera. Keratin analysis can give new insights in epithelial maturation and may be helpful for the classification of oral leukoplakia.


Extra-cellular matrix rigidity may dictate the fate of injury outcome.
After injury, while regeneration can be observed in hydra, planaria and some vertebrates, regeneration is rare in mammals and particularly in humans. In this paper, we investigate the mechanisms by which biological tissues recover after injury. We explore this question on adipose tissue, using the mathematical framework recently developed in Peurichard et al., J. Theoret. Biol. 429 (2017), pp. 61-81. Our assumption is that simple mechanical cues between the Extra-Cellular Matrix (ECM) and differentiated cells can explain adipose tissue morphogenesis and that regeneration requires after injury the same mechanisms. We validate this hypothesis by means of a two-dimensional Individual Based Model (IBM) of interacting adipocytes and ECM fiber elements. The model successfully generates regeneration or scar formation as functions of few key parameters, and seems to indicate that the fate of injury outcome could be mainly due to ECM rigidity.


Off-line setup corrections only marginally reduce the number of on-line corrections for prostate radiotherapy using implanted gold markers.
To evaluate the efficiency of combining on-line and off-line corrections for the positioning of patients receiving external beam radiotherapy for prostate cancer. Daily portal images were acquired during the treatment of 102 patients to verify and correct the position of the prostatic gland using implanted gold markers. In addition to an existing off-line procedure, on-line corrections were applied in the anterior-posterior (AP) direction only, to limit the increase in daily workload. The possible increase in workload of the combined correction procedure for on-line corrections in either two or three directions was further investigated by simulating the required position corrections for 500 treatments. The combined correction procedure in AP-direction resulted in a systematic dispersion and random variation of 0.3mm (1 SD) and 1.0mm (1 SD), respectively. Application of off-line corrections during pre-treatment setup reduced the number of required on-line corrections from 22+/-4 (1 SD) to 17+/-4 (1 SD), at the cost of 1.4+/-1.0 (1 SD) off-line corrections. For on-line corrections in two or three directions, application of a combined on-line/off-line procedure did not noticeably reduce the number of setup corrections. The on-line procedure is feasible and significantly improves both systematic and random errors to below 1 mm with a limited impact on the workload and treatment time. The application of off-line setup corrections during pre-treatment patient positioning only marginally reduces the number of on-line setup corrections.


Prevalence, quantification and typing of adenoviruses detected in river and treated drinking water in South Africa.
Human adenoviruses (HAds), of which there are 51 serotypes, are associated with gastrointestinal, respiratory, urinary tract and eye infections. The importance of water in the transmission of HAds and the potential health risks constituted by HAds in these environments are widely recognized. Adenoviruses have not previously been quantified in river and treated drinking water samples. In this study, HAds in river water and treated drinking water sources in South Africa were detected, quantified and typed. Adenoviruses were recovered from the water samples using a glass wool adsorption-elution method followed by polyethylene glycol/NaCl precipitation for secondary concentration. The sensitivity and specificity of two nested PCR methods were compared for detection of HAds in the water samples. Over a 1-year period (June 2002 to July 2003), HAds were detected in 5.32% (10/188) of the treated drinking water and 22.22% (10/45) of river water samples using the conventional nested PCR method. The HAds detected in the water samples were quantified using a real-time PCR method. The original treated drinking water and river water samples had an estimate of less than one copy per litre of HAd DNA present. The hexon-PCR products used for typing HAds were directly sequenced or cloned into plasmids before sequencing. In treated drinking water samples, species D HAds predominated. In addition, adenovirus serotypes 2, 40 and 41 were each detected in three different treated drinking water samples. Most (70%) of the HAds detected in river water samples analysed were enteric HAds (serotypes 40 and 41). One HAd serotype 2 and two species D HAds were detected in the river water. Adenoviruses detected in river and treated drinking water samples were successfully quantified and typed. The detection of HAds in drinking water supplies treated and disinfected by internationally recommended methods, and which conform to quality limits for indicator bacteria, warrants an investigation of the risk of infection constituted by these viruses. The risk of infection may have implications for the management of drinking water quality. This study is unique as it is the first report on the quantification and typing of HAds in treated drinking water and river water. This baseline data is necessary for the meaningful assessment of the potential risk of infection constituted by these viruses.


Dorsal locking of the metacarpophalangeal joint.
Many causes for metacarpophalangeal joint locking have been documented. However nearly all are from volar entrapment of periarticular structures. The following case, unlike those previously reported in the literature, was one with locking caused by dorsal entrapment. The differences in presentation and its importance to subsequent treatment are highlighted.


Determination of contrast medium dose for hepatic CT enhancement with improved body size dependency using a non-linear analysis based on pharmacokinetic principles.
To propose a pharmacokinetic non-linear analysis method to determine contrast medium (CM) dose for computed tomography (CT) hepatic enhancement to improve body size dependency and validate the proposed CM dose determination method through a clinical study. Enhancement data of 105 patients who underwent hepatic dynamic CT with a fixed CM dose were analysed. From the analysis results, CM doses as a function of each of four body size indices (body weight [BW], lean body weight [LBW], blood volume [BV], and body surface area [BSA]) for achieving improved body size dependency were determined (proposed method), and the body size dependencies were simulated using the enhancement data from 105 patients. The proposed method was validated with a two-arm clinical study on BW. Body size dependency was evaluated using p-value of correlation coefficient between Body size indices and enhancements (p<0.05: significant dependency) and mean absolute error (MAE). The simulation showed that significant body size dependencies not considered by the conventional method can be improved by the proposed method. MAEs of BW, LBW, and BV were also significantly reduced (p<0.05). The clinical study with BW demonstrated a similar improvement to that in the simulation result. MAE was also significantly reduced (p<0.001). The proposed method demonstrated more improved BW, LBW, and BV dependence compared to the conventional method. Through the two-arm clinical study, the proposed method using BW only, without height information, is a suitable index for improving body size dependency.


The relationship between primary cognitive appraisals, illness beliefs, and adaptation to rheumatoid arthritis: A systematic review and meta-analysis.
Rheumatoid arthritis is a chronic disease that negatively affects functioning; however, the relationship between cognitive appraisals and illness-related beliefs and adaptation indices remains unclear. The aim of this review was to assess the relationship between cognitive appraisals, illness beliefs and indicators of adaptation to life with a chronic disease, such as the severity of depressive symptoms, anxiety, and quality of life. A database search was carried out between May 13 and 18, 2022, with no time restrictions. Thirty studies (5 related to cognitive appraisals, 25 related to illness beliefs) were identified. The studies identified in the review were of satisfactory quality. An analysis of the articles allowed for a meta-analysis focusing on the relationship between the belief related to illness consequences and the severity of depressive symptoms, which gave an overall correlation estimate of 0.50 [0.44-0.56]. Both cognitive appraisals and illness beliefs are related to indicators of rheumatoid arthritis adaptation, such as depressive symptom severity, anxiety and acceptance levels. Further longitudinal research would be crucial in further elucidating the impact of cognitive factors on adjustment level and its trajectories over time. Review was pre-registered at https://osf.io/gd9cw (DOI:http://10.17605/OSF.IO/GD9CW).


Late complications after pancreaticoduodenectomy with pancreaticogastrostomy.
We investigated complications after pancreaticoduodenectomy (PD) with pancreaticogastrostomy (PG) reconstruction more than 12 months postoperatively. Through chart review and outpatient follow-up, we assessed the incidence of new-onset diabetes mellitus (DM) and steatorrhea after PD. Ninety patients underwent PD with PG with a median follow-up of 4.7 years (range 0.4-15.8 years). Of the 77 patients without DM preoperatively, 18 (23.4%) developed DM postoperatively. Those who developed DM were younger at time of surgery than those who did not (60.5 versus 65.8 years; p = 0.021), but postoperative survival did not differ between these groups. The incidence of DM was comparable to the incidence of DM in the general population. Out of 89 patients, 47 (52.8%) now require pancreatic enzyme therapy. The group that developed steatorrhea underwent PD at a younger age (61.4 versus 67.0 years; p = 0.029). Patients that undergo PD at a younger age are more likely to develop DM and steatorrhea than their older counterparts; patients are as likely as the general population, however, to develop DM after PD with PG.


Identification of annotation artifacts concerning the chalcone synthase (CHS).
Chalcone synthase (CHS) catalyzes the initial step of the flavonoid biosynthesis. The CHS encoding gene is well studied in numerous plant species. Rapidly growing sequence databases contain hundreds of CHS entries that are the result of automatic annotation. In this study, we evaluated apparent multiplication of CHS domains in CHS gene models of four plant species. CHS genes with an apparent triplication of the CHS domain encoding part were discovered through database searches. Such genes were found in Macadamia integrifolia, Musa balbisiana, Musa troglodytarum, and Nymphaea colorata. A manual inspection of the CHS gene models in these four species with massive RNA-seq data suggests that these gene models are the result of artificial fusions in the annotation process. While there are hundreds of seemingly correct CHS records in the databases, it is not clear why these annotation artifacts appeared.


A review of novel green adsorbents as a sustainable alternative for the remediation of chromium (VI) from water environments.
The presence of heavy metal, chromium (VI), in water environments leads to various diseases in humans, such as cancer, lung tumors, and allergies. This review comparatively examines the use of several adsorbents, such as biosorbents, activated carbon, nanocomposites, and polyaniline (PANI), in terms of the operational parameters (initial chromium (VI) concentration (Co), temperature (T), pH, contact time (t), and adsorbent dosage) to achieve the Langmuir's maximum adsorption capacity (qm) for chromium (VI) adsorption. The study finds that the use of biosorbents (fruit bio-composite, fungus, leave, and oak bark char), activated carbons (HCl-treated dry fruit waste, polyethyleneimine (PEI) and potassium hydroxide (KOH) PEI-KOH alkali-treated rice waste-derived biochar, and KOH/hydrochloric acid (HCl) acid/base-treated commercial), iron-based nanocomposites, magnetic manganese-multiwalled carbon nanotubes nanocomposites, copper-based nanocomposites, graphene oxide functionalized amino acid, and PANI functionalized transition metal are effective in achieving high Langmuir's maximum adsorption capacity (qm) for chromium (VI) adsorption, and that operational parameters such as initial concentration, temperature, pH, contact time, and adsorbent dosage significantly affect the Langmuir's maximum adsorption capacity (qm). Magnetic graphene oxide functionalized amino acid showed the highest experimental and pseudo-second-order kinetic model equilibrium adsorption capacities. The iron oxide functionalized calcium carbonate (IO@CaCO3) nanocomposites showed the highest heterogeneous adsorption capacity. Additionally, Syzygium cumini bark biosorbent is highly effective in treating tannery industrial wastewater with high levels of chromium (VI).


Is there a role for locoregional treatment of the primary tumor in de novo metastatic breast cancer in the era of tailored therapies?: Evidences, unresolved questions and a practical algorithm.
Improvements in systemic therapies have changed the face of de novo metastatic breast cancer (dnMBC), with a 5-year survival rate exceeding 25 %. Increasing evidence suggests that a subset of patients could benefit from a locoregional treatment (LRT) with prolonged survival, although the diversity of publications on the subject make it difficult to draw any conclusions. In this review, we summarize the available data on retrospective, prospective and current ongoing clinical trials. Since factors such as tumor biology, pattern of metastatic dissemination and the timing of the treatment are closely linked to the therapeutic strategy, we focus on papers which include these aspects. We discuss recent studies indicating that exclusive radiotherapy provides results comparable with those obtained by surgery. We will then discuss the biological rationale for LRT. Finally, we propose a decision-tree to select the optimal candidates for LRT in dnMBC patients.


The effect of the type A behaviour pattern on myocardial ischaemia during daily life.
Twenty-eight subjects completed 2 Type A questionnaires. Just under half the patients were considered Type A. Painful episodes of myocardial ischaemia occurred more frequently in Type A patients during a stressful period of ambulatory Holter monitoring compared to a later date. This difference could not be explained in terms of severity of disease or length of myocardial ischaemia. Rather it seemed to reflect increased reporting of somatic symptoms on the background of a greater sensitivity to environmental stress. Type A patients may thus present themselves earlier than their Type B peers.


Prevalence and risk factors for allergic rhinitis and atopic eczema among schoolchildren in Israel: results from a national study.
There is growing evidence that the prevalence rates of asthma and allergic diseases are increasing, especially among children. Several risk factors are under investigation. To evaluate the prevalence and risk factors for allergic diseases, including allergic rhinitis (AR) and atopic eczema (AE), among 13- to 14-year-old schoolchildren in Israel. A modified version of the International Study of Asthma and Allergies in Childhood written questionnaire was administered to a national sample of schoolchildren 13 to 14 years old in Israel. The questionnaire was completed by the schoolchildren themselves. There were 10,057 complete questionnaires available for analysis. The prevalence of AR symptoms ever and current AR were 41.6% and 9.4%, respectively. Allergic rhinoconjunctivitis symptoms ever were reported by 15.8% of the children. The prevalence rates of 6 months of itchy rash ever and AE were 5.9% and 7.8%, respectively. After adjustment for demographic and environmental factors, current asthma, parental history of asthma, and population group were the most significant risk factors for current AR (odds ratio [OR], 4.47; 95% confidence interval [CI], 3.70-5.40; OR, 1.30; 95% CI, 1.02-1.66; and OR, 1.75; 95% CI 1.45-2.13; respectively) and AE (OR, 2.30; 95% CI, 1.80-2.90; OR, 1.80; 95% CI, 1.40-2.30; and OR, 1.70; 95% CI, 1.40-2.00; respectively). Israeli children have a low prevalence rate of current AR and a midrange rate of AE. Arabs have lower prevalence rates of allergic diseases than Jews, and the prominent risk factors for those diseases are current asthma and parental history of asthma.


Exploiting cell surface thiols to enhance cellular uptake.
Efficient cellular delivery is one of the key issues that has hampered the therapeutic development of novel synthetic biomolecules such as oligonucleotides, peptides and nanoparticles. The highly specialized cellular plasma membrane specifically internalizes compounds through tightly regulated mechanisms. It is possible to exploit these natural mechanisms of cellular uptake with rationally designed reagents. Here, we discuss how thiol groups (-SH) naturally present on the cell surface (exofacial thiols) can be used to enhance cellular association and internalization of various materials bearing thiol-reactive groups in their structure. We propose that such thiol modifications should be considered in future design of synthetic biomolecules for optimized cellular delivery.


Kinetic-exclusion analysis-based immunosensors versus enzyme-linked immunosorbent assays for measurement of cancer markers in biological specimens.
Kinetic exclusion analysis (KinExA)-based immunosensors and enzyme-linked immunosorbent assays (ELISA) have been developed and validated for measurement of five different cancer markers in biological specimens. These markers were: 2'-deoxycytidine (dCyd), 8-hydroxy-2'-deoxyguanosine (8HdG), carbohydrate antigen (CA15-3), α-fetoprotein (AFP), and β-subunit of human chorionic gonadotropin (β-HCG). The KinExA-based assays were conducted on the KinExA™ 3200 instrument. The ELISA assays employed the competitive immunoassay format for dCyd and 8HdG, however they employed the direct sandwich-type format for CA15-3, AFP, and β-HCG. Each assay was validated in terms of its limit of detection, working range, precision profile, and accuracy. The analytical performances of the KinExA-based sensors were found to be superior to the ELISA for the five markers. The data demonstrated that the format of the assay may influence its performance characteristics (sensitivity, precision, etc.), even when exactly the same reagents are employed. The superior performance of the KinExA format is most likely due to: (1) the high surface area of beads containing the immobilized capture in the flow cell of the instrument, (2) the high flow rate of the reagents passing through the beads, which minimizes the diffusion limitations at the reaction surface, and (3) the limited time that the antibody is in contact with the capture reagent. The KinExA-based assays exhibited three noteworthy properties compared with ELISA: (1) avoiding the problems of mass transport limitations, and mobility effects, (2) KinExA analysis with automated sampling increase the assay convenience; and (3) providing high sensitivity with a lower limit of detection and better precision than ELISA. The proposed KinExA-based immunosensors are anticipated to have a great value in measurement of the cancer markers where more confident results are needed.


Nitrofurazone: vas irrigation as an adjunct in vasectomy.
Intraoperative vas irrigation with nitrofurazone utilized in a 1-mg/ml concentration can cause immediate sterility postoperatively. This irrigation procedure adds little time to the standard vasectomy and can easily be performed as an outpatient office procedure, minimizing time-consuming postoperative semen analyses. Moreover, in developing countries where postoperative vasectomy follow-up may be more difficult to obtain and may even be nonexistent, this procedure would provide an additional positive factor in an attempt to ensure sterility.


Takayasu arteritis with multiple cardiovascular complications.
A 60-year-old Japanese woman first presented in 1990 with effort angina. She underwent coronary angiography and was diagnosed with bilateral coronary ostial stenosis and Takayasu arteritis. Coronary artery bypass graft surgery (CABG) for multiple vessels was attempted, but the blood flow in the bilateral internal thoracic and gastroepiploic arteries was to poor for a donor artery, and the calcification of the ascending aortic wall was too severe for anastomosis of saphenous vein grafts. Therefore, the proper hepatic artery was connected to the left anterior descending artery using a vein graft. In April 2000, the patient's angina worsened. Occlusions of both subclavian arteries, bilateral coronary ostial stenosis and vein graft occlusion, aortic valve regurgitation, and two severe stenoses of the descending aorta were observed. Aortic valve replacement, and coronary and aorta revascularization were desirable, but the severe aortic wall calcification and thickening rendered these interventions impossible. Treatment with medication was chosen. The patient was discharged without severe angina. A combination of these serious cardiovascular complications which do not allow any surgical intervention is very rare.


Cnga2 Knockout Mice Display Alzheimer's-Like Behavior Abnormities and Pathological Changes.
Olfactory dysfunction is recognized as a potential risk factor for Alzheimer's disease (AD). We have reported previously that olfactory deprivation by olfactory bulbectomy (OBX) induced Alzheimer's-like pathological changes and behavioral abnormalities. However, the acute OBX model undergoes surgical-induced brain parenchyma loss and unexpected massive hemorrhage so that it cannot fully mimic the progressive olfactory loss and neurodegeneration in AD. Here, we employed the mice loss of cyclic nucleotide-gated channel alpha 2 (Cnga2) which is critical for olfactory sensory transduction, to investigate the role of olfactory dysfunction in AD pathological process. We found that impaired learning and memory abilities, loss of dendrite spines, as well as decrement of synaptic proteins were displayed in Cnga2 knockout mice. Moreover, Aβ overproduction, tau hyperphosphorylation, and somatodendritic translocation were also found in Cnga2 knockout mice. Our findings suggest that progressive olfactory loss leads to Alzheimer's-like behavior abnormities and pathological changes.


Effector lymphocyte response to homologous tumor antigens in various stages of malignant disease as monitored by leukocyte adherence inhibition--cell mediated immunity (LAI-CMI).
Leukocyte adherence inhibition-cell mediated immunity (LAI-CMI) studies were performed on leukocytes obtained from patients with various stages of breast cancer, colon carcinoma and lung cancer in order to monitor cell mediated immunity during tumor progression. In the presence of autologous serum, all patients with localized tumors showed positive LAI-CMI indexes (greater than 20%), while significant reduction of homologous tumor antigen recognition as measured by the LAI-CMI responses was observed in nearly all patients with Stage IV breast cancer, Duke C colon cancer and Stage III lung cancer. On substituting autologous serum with normal AB serum, leukocytes from patients with large tumor burdens responded to homologous tumor antigens. These results indicate the existence of organ-specific serum factor(s) which may mask the receptor sites on effector cells for tumor recognition. Patients with such serum blocking factor(s) showed significant increase of IgG immune complexes IgM, IgA and alpha-2-macroglobulins. Application of a protein A affinity column purification resulted in a major reduction of IgG and other immune globulins but not of alpha-2-macroglobulin. The blocking effects of autologous serum, however, were not completely abrogated by filtration on the protein A column, thus suggesting that SBF may be heterogeneous in nature and may occur in other serum protein fractions beside the immune globulins.


Defining sepsis.
Definitions have been considered important in all fields of medicine, both at a patient level to facilitate accurate diagnosis and treatment, and at a research level to clarify patient inclusion criteria and interpretation of study results. Although there is agreement that sepsis refers to the host response to infection, the complexity of this response and of the patient groups affected, however, has meant that establishing accepted definitions of sepsis has been difficult. Recent consensus has provided global definitions of sepsis and infection, but further work is necessary to provide a means of more completely characterizing the sepsis response in individual patients, such that new interventions can be targeted better as physicians strive to decrease the still high mortality rates associated with this condition.


[State policy at the end of life. The transformation of medical deontology].
The contemporary state invades privacy in ways that affect even the end of life process. It develops public policies that can affect medical ethics. This limitation of power leaves the doctor's attention to the profession and may become a convenient code.


Effect of cadmium on lymphocyte subsets distribution in thymus and spleen.
This work was designed to analyze the possible dose dependent effects of cadmium on the distribution of lymphocyte subsets within the thymus and spleen. Cadmium accumulation was also evaluated in these tissues. For this purpose, adult male rats were exposed for one month to 0, 5, 10, 25, 50 or 100 ppm of cadmium chloride (CdCl2) in the drinking water. In both spleen and thymus, the B lymphocytes increased with the doses of 5 and 10 ppm of CdCl2, and decreased with the doses of 25-100 ppm. In spleen, the doses of 25 and 50 ppm decreased CD4+ cells and the doses of 5 and 10 ppm increased CD8+ cells, while the percentage of thymus T, CD4+, CD8+ and CD4(+)-CD8+ cells was not modified by cadmium treatment at any dose used in this study. After cadmium exposure, the metal was accumulated in the spleen only from the dose of 50 ppm on, and in the thymus, from the dose of 10 ppm on. In conclusion, although the accumulation of the metal is higher in thymus than in spleen, the metal affected CD4+ and CD8+ lymphocytes at the spleen but not at the thymus.


Lingering Dynamics in Microvascular Blood Flow.
The microvascular networks in the body of vertebrates consist of the smallest vessels such as arterioles, capillaries, and venules. The flow of red blood cells (RBCs) through these networks ensures the gas exchange in as well as the transport of nutrients to the tissues. Any alterations in this blood flow may have severe implications on the health state. Because the vessels in these networks obey dimensions similar to the diameter of RBCs, dynamic effects on the cellular scale play a key role. The steady progression in the numerical modeling of RBCs, even in complex networks, has led to novel findings in the field of hemodynamics, especially concerning the impact and the dynamics of lingering events when a cell meets a branch of the network. However, these results are yet to be matched by a detailed analysis of the lingering experiments in vivo. To quantify this lingering effect in in vivo experiments, this study analyzes branching vessels in the microvasculature of Syrian golden hamsters via intravital microscopy and the use of an implanted dorsal skinfold chamber. It also presents a detailed analysis of these lingering effects of cells at the apex of bifurcating vessels, affecting the temporal distribution of plasmatic zones of blood flow in the branches and even causing a partial blockage in severe cases.


Simultaneous immunochemical detection of stanozolol and the main human metabolite, 3'-hydroxy-stanozolol, in urine and serum samples.
Two enzyme-linked immunosorbent assays (ELISAs) have been established for the analysis of stanozolol (St) and 3'-hydroxy-stanozolol (3'OH-St), the main metabolite found in humans. The immunizing hapten N2'-(5-valeric acid)-androst-2-eno[3,2-c]-pyrazol-17a-methyl-17b-ol (hapten 8) has been designed with the aid of molecular modeling and theoretical tools to allow immunochemical detection of both compounds. Using an ELISA based on a homologous antisera/coating antigen combination, St can be selectively quantified without significant interference of the St metabolites or other steroids potentially present in the biological samples. On the other hand, St immunoreactivity equivalents due to the additional presence of 3'OH-St can also be quantified using an ELISA based on a heterologous antisera/coating antigen combination, in which the metabolite can be detected with 51% cross-reactivity. Thus, As147/5BSA detects 3'OH-St and St in buffer with IC(50) values of 1.46 and 0.68 microg L(-1), respectively. In contrast, As147/8BSA is highly specific for St with an IC(50) of 0.16 microg L(-1) and a limit of dection of just 0.022 microg L(-1). Performance of both assays in urine and serum samples has been evaluated and demonstrate that inappropriate use of stanozolol by athletes or young people can be detected in these matrices after simple cleanup methods, with IC(50) values below the minimum performance required levels established by the World Antidoping Agency.


A new reaction mode of germanium-silicon bond formation: insertion reactions of H₂GeLiF with SiH₃X (X = F, Cl, Br).
A combined density functional and ab initio quantum chemical study of the insertion reactions of the germylenoid H2GeLiF with SiH3X (X = F, Cl, Br) was carried out. The geometries of all the stationary points of the reactions were optimized using the DFT B3LYP method and then the QCISD method was used to calculate the single-point energies. The theoretical calculations indicated that along the potential energy surface, there were one precursor complex (Q), one transition state (TS), and one intermediate (IM) which connected the reactants and the products. The calculated barrier heights relative to the respective precursors are 102.26 (X = F), 95.28 (X = Cl), and 84.42 (X = Br) kJ mol(-1) for the three different insertion reactions, respectively, indicating the insertion reactions should occur easily according to the following order: SiH3-Br > SiH3-Cl > SiH3-F under the same situation. The solvent effects on the insertion reactions were also calculated and it was found that the larger the dielectric constant, the easier the insertion reactions. The elucidations of the mechanism of these insertion reactions provided a new reaction model of germanium-silicon bond formation.


Multifidus muscle size and symmetry among elite weightlifters.
To examine muscle cross-sectional areas (CSA) and symmetry of lumbar multifidus (LM) muscles in elite weightlifters. Cross-sectional observational study Neuromuscular and Pain Research Unit. Thirty-one elite weightlifters (15 males) participated in the study, representing the population of Thai weightlifters eligible for national selection. Resting CSA of the LM muscle were assessed bilaterally at 4 lumbar vertebral levels using ultrasound imaging. The between side differences (relative to the side of the preferred hand) were used to determine the asymmetry. The between side differences (relative to the preferred hand) of the LM muscle CSA were less than 3% for all vertebral levels and suggested symmetry between sides (p > .05). No difference was found between weightlifters with unilateral or bilateral pain symptoms. This study provides new information on resting CSA for the LM muscle in elite weightlifters. Future studies could investigate other aspects of neuromotor control of the LM muscle to determine if there are impairments which could be addressed in an attempt to decrease the high prevalence of LBP in this population.


Intrinsic excitation in the rat neostriatum mediated by acetylcholine.
Synaptic excitation elicited by local stimulation in neostriatal slices was found to be mediated by acetylcholine (ACh). The synapses generating this excitation belong to intrinsic neurons. Thus, for the first time, direct evidence for the existence of intrinsic excitatory cholinergic neurons in the neostriatum is provided.


Mining the Proteome of Streptococcus mutans for Putative Drug Targets.
Dental caries is the most common and one of the prevalent diseases in the world. Streptococcus mutans is one of the major oral pathogens that cause dental caries by forming a biofilm on dental tissues, degrading dental enamel and consequent cavitation in the tissue. In vitro selection of drug targets is a laborious and expensive process and therefore, computational methods are preferable for target identification at the initial stage. The present research aims to find new drug targets in S. mutans by using subtractive proteomics analysis, which implements various bioinformatics tools and databases. The proteome of S. mutans UA159 was mined for novel drug targets using computational tools and databases such as: CD-HIT, BLASTP, DEG, KAAS and CELL2GO. Out of 1953 proteins of S. mutans UA159, proteins that are redundant, homologous to human and non-essential to the pathogen were eliminated. Around 178 proteins already available in drug target repositories were also eliminated. Possible functions and subcellular localization of 32 uncharacterized proteins were predicted. Substantially, 13 proteins were identified as novel drug targets in S. mutans UA159 that can be targeted by various drugs against dental caries. This study will effectuate the development of novel therapeutic agents against dental caries and other Streptococcal infections.


Encephalomyelitis and myositis in a boxer puppy due to a Neospora-like infection.
A 10-week-old Boxer dog from Uppsala, Sweden, was killed because of hind limb paralysis. The hind limb muscles were grossly atrophied and encephalomyelitis and myositis were the predominant microscopic lesions. Neospora caninum-like tachyzoites were found in the brain and skeletal muscles, and tissue cysts were found in the brain. The organism was not Toxoplasma gondii, as T. gondii antibody was not found in the indirect fluorescent antibody test in serum samples from the puppy and the dam, and the organism in the dog's brain did not react with T. gondii antibody in the immunoperoxidase test.


A study on the effect of cimetidine and L-carnitine on myoglobinuric acute kidney injury in male rats.
Myoglobinuric acute renal failure is the most important life threatening complication of rhabdomyolysis. Iron, free radicals, nitric oxide and cytochrome p450 are involved in the pathogenesis of mARF. The aim of this study is to compare the effect of cimetidine, l-carnitine and both agents together on mARF in rats. Forty rats were divided into 5 groups; group I: control rats, group II: myoglobinuric ARF rats, group III: mARF rats received l-carnitine (200mg/kg, i.p.), group IV: mARF rats received cimetidine (150mg/kg i.p.) and group V: mARF rats received both agents together. 48h after glycerol injection, systolic blood pressure was measured. Urine and blood samples were collected to evaluate urine volume, GFR, BUN, creatinine, K, Na, serum creatine kinase, NO and glutathione levels. Kidney specimens were taken to investigate renal cytochrome p450 and for histological examinations. Cimetidine treatment significantly decreased creatinine, BUN, K, Na, SBP and creatine kinase and increased GFR and urine volume compared to group II. l-carnitine exerted similar changes except for the effect on K and GFR. NO was significantly decreased, while renal glutathione and cytochrome p450 were significantly increased in groups treated with l-carnitine or cimetidine as compared to group II. Combined treatment further improved renal functions, creatine kinase, oxidative stress parameters and SBP as compared to each therapy alone. The histological changes confirmed the biochemical findings. Cimetidine and l-carnitine have protective effects - almost equally - against mARF. Using both agents together, minimises the renal injury.


In vivo effect of pressurization of polymethyl methacrylate bone-cement. Biomechanical and histologic analysis.
Sixteen goats underwent total hip arthroplasty, half with pressurized and half with unpressurized bone-cement. The animals underwent hemiarthroplasty of the contralateral hip immediately prior to sacrifice 6 weeks later. Samples were tested for interface strength and evaluated histologically. Pressurization of polymethyl methylacrylate improves the strength of the bone-cement interface in vivo, as well as in vitro. There is a regional variation in the strength of the bone-cement interface both in vivo and in vitro. The regional variation in the in vivo model is at least in part due to a biologic effect. Membranes forming at the bone-cement interface are usually fibrous and incomplete, allowing direct cement-to-bone contact. Membranes appear to be involved in the remodeling of bone. Polymethyl methacrylate causes significant necrosis of the cortex, with ensuing resorption of the cortical bone. There is a small, statistically insignificant trend toward increased resorption and decreased bone formation with pressurized cement. The amount of necrosis appears to be similar with pressurized and nonpressurized cement. Bone remodels to fill defects in the cement mantle.


Copper-2 Ingestion, Plus Increased Meat Eating Leading to Increased Copper Absorption, Are Major Factors Behind the Current Epidemic of Alzheimer's Disease.
It has become clear that copper toxicity is playing a major role in Alzheimer's disease; but why is the brain copper toxicity with cognition loss in Alzheimer's disease so much different clinically than brain copper toxicity in Wilson's disease, which results in a movement disorder? Furthermore, why is the inorganic copper of supplement pills and in drinking water so much more damaging to cognition than the organic copper in food? A recent paper, which shows that almost all food copper is copper-1, that is the copper-2 of foods reverts to the reduced copper-1 form at death or harvest, gives new insight into these questions. The body has an intestinal transport system for copper-1, Ctr1, which channels copper-1 through the liver and into safe channels. Ctr1 cannot absorb copper-2, and some copper-2 bypasses the liver, ends up in the blood quickly, and is toxic to cognition. Humans evolved to handle copper-1 safely, but not copper-2. Alzheimer's is at least in part, a copper-2 toxicity disease, while Wilson's is a general copper overload disease. In this review, we will show that the epidemiology of the Alzheimer's epidemic occurring in developed, but not undeveloped countries, fits with the epidemiology of exposure to copper-2 ingestion leached from copper plumbing and from copper supplement pill ingestion. Increased meat eating in developed countries is also a factor, because it increases copper absorption, and thus over all copper exposure.


Study of water-conducting fractured zone development law and assessment method in longwall mining of shallow coal seam.
Starting from the source of mining, scientific understanding of surface damage law and assessment method in longwall mining of shallow coal seam is conducive to solving the problems of geological hazards and deterioration of the ecological environment, and promoting the coordinated development of efficient coal mining and environmental protection. Based on numerical simulation and theoretical analysis, the surface damage process and spatiotemporal evolution of fracture field are discussed. The influencing factors and assessment method of surface damage are clarified. The results show that surface damage undergone the immediate roof caving stage, the fracture and instability stage of main roof, the spatial amplification stage of separation layer, the instability stage of surface damage control layer and the mining damage stability stage. Under the critical extraction condition, the cracks above the goaf are divided into the crack area outside the cut, the crack area inside the cut, the re-compaction area in the middle goaf, the crack area behind the longwall face, and the crack area in front of the longwall face. The overburden reaches critical failure ahead of surface critical mining. The sensitivity of loose layer thickness to surface subsidence coefficient is greater than that of mining thickness to surface subsidence coefficient. Surface damage control should be adjusted to local conditions, and finally realize zoning treatment and zoning repair. Through the three-step method of "longwall face rapid advancing method, local grouting reinforcement overburden method and zoning treatment ground fissures method", the surface damage control of 12,401 longwall face is realized. This research provides theoretical guidance and application value for surface ecological restoration in similar mining area.


Zygomatic fractures managed by closed reduction: an analysis with postoperative computed tomography follow-up evaluating the degree of reduction and remaining dislocation.
To evaluate possible associations between the degree of reduction, remaining dislocation (mm), fracture type, and the sequelae from which the patient may suffer postoperatively in patients with zygomaticomaxillary fracture managed by closed reduction. A 3-year retrospective audit was undertaken to identify all patients who had sustained a fractured zygoma and were operated on by closed reduction at the Ear, Nose, and Throat Department, Karolinska University Hospital, Huddinge, Sweden. Patients were followed up by mail questionnaire and postoperative computed tomography (CT). The odds of having symptoms (odds ratio [OR] 4.26, confidence interval [CI] 1.09-18.44) was significantly higher in the group with a reduction less than 100% (n = 34) compared with the group with 100% reduction (n = 17) (P = .035). The odds of having symptoms (OR 9.91, CI 0.89->500) was higher in the group with remaining dislocation 6 to 10 mm compared with the group with no remaining dislocation (P = .069). The type of fracture (A, B, or C) also influenced the patients' postoperative symptoms. The odds of having symptoms was 48.40 (CI 4.60->500) times higher having fracture C compared with fracture A (P < .001). The degree of reduction and remaining dislocation of zygomaticomaxillary fractures is important to achieve a good postoperative result, that is, reducing the patient's postoperative symptoms. Furthermore, the type of fracture also influences the patient's long-term sequelae.


Fluorescent histochemical demonstration of cathepsin B in the rat yolk sac.
Fluorescence demonstration of cathepsin B (E.C. 220.127.116.11) activity was performed in the yolk sac of rats near term (18th day of gestation). The enzyme demonstration was performed on freeze-dried and celloidin mounted yolk-sac sections using different substituted beta-naphthylamide derivatives as substrates and nitrosalicylaldehyde as coupling agent. The discrete reaction products are localized preferentially in the apical part of the visceral yolk-sac epithelium. There is little doubt that cathepsin B is contained here in the well developed lysosomal apparatus of the yolk-sac epithelium.


A longitudinal study of iron status in children at 12, 24 and 36 months.
To assess iron status in a sample of clinically well, Caucasian children and explore the complex factors which contribute to iron deficiency during infancy. Infants recruited at birth and followed longitudinally at 1, 2, 3, 4, 5, 6, 9, 12, 24 and 36 months; feeding practices and socioeconomic data recorded. Iron status assessed using venous blood at 12, 24 and 36 months. Baseline data recorded in the maternity unit. Follow-up visits took place in the infants' homes and blood sampling in a paediatric hospital. Subjects comprised a mixed socioeconomic group of healthy children (n = 121). Blood samples taken from 85, 72 and 67% at 12, 24 and 36 months, respectively. Prevalence of anaemia (Hb < 110 g l(-1)) in the longitudinal sample (n = 76) increased from 2.6% at age 12 months to 9.2% at 24 months, and at age 36 months (n = 70) was 8%. The most significant finding was that at age 12 months, cows' milk consumption was negatively associated with iron status. Other variables also had an influence. At both 24 and 36 months the most significant predictor of iron status was earlier iron status. Infants born to anaemic mothers or mothers who smoke and infants who consume cows' milk during infancy are at increased risk of developing anaemia. Breast milk is the ideal, but for the infant who is not breast fed an iron fortified formula should be used. Advice to mothers should focus on the importance of introducing nutrient dense complementary foods, such as meat, which contains readily absorbable iron.


Regulation of GABAARs by Transmembrane Accessory Proteins.
The vast majority of fast inhibitory transmission in the brain is mediated by GABA acting on GABAA receptors (GABAARs), which provides inhibitory balance to excitatory drive and controls neuronal output. GABAARs are also effectively targeted by clinically important drugs for treatment in a number of neurological disorders. It has long been hypothesized that function and pharmacology of GABAARs are determined by the channel pore-forming subunits. However, recent studies have provided new dimensions in studying GABAARs due to several transmembrane proteins that interact with GABAARs and modulate their trafficking and function. In this review, we summarize recent findings on these novel GABAAR transmembrane regulators and highlight a potential avenue to develop new GABAAR psychopharmacology by targeting these receptor-associated membrane proteins.


Polyhydroxyalkanoates are essential for maintenance of redox state in the Antarctic bacterium Pseudomonas sp. 14-3 during low temperature adaptation.
Polyhydroxyalkanoates (PHAs) are highly reduced bacterial storage compounds that increase fitness in changing environments. We have previously shown that phaRBAC genes from the Antarctic bacterium Pseudomonas sp. 14-3 are located in a genomic island containing other genes probably related with its adaptability to cold environments. In this paper, Pseudomonas sp. 14-3 and its PHA synthase-minus mutant (phaC) were used to asses the effect of PHA accumulation on the adaptability to cold conditions. The phaC mutant was unable to grow at 10 degrees C and was more susceptible to freezing than its parent strain. PHA was necessary for the development of the oxidative stress response induced by cold treatment. Addition of reduced compounds cystine and gluthathione suppressed the cold sensitive phenotype of the phaC mutant. Cold shock produced very rapid degradation of PHA in the wild type strain. The NADH/NAD ratio and NADPH content, estimated by diamide sensitivity, decreased strongly in the mutant after cold shock while only minor changes were observed in the wild type. Accordingly, the level of lipid peroxidation in the mutant strain was 25-fold higher after temperature downshift. We propose that PHA metabolism modulates the availability of reducing equivalents, contributing to alleviate the oxidative stress produced by low temperature.


The influence of the 'organizational factor' on compound quality in drug discovery.
Physicochemical properties such as lipophilicity and molecular mass are known to have an important influence on the absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of small-molecule drug candidates. To assess the use of this knowledge in reducing the likelihood of compound-related attrition, the molecular properties of compounds acting at specific drug targets described in patents from leading pharmaceutical companies during the 2000-2010 period were analysed. Over the past decade, there has been little overall change in properties that influence ADMET outcomes, but there are marked differences in molecular properties between organizations, which are maintained when the targets pursued are taken into account. The target-unbiased molecular property differences, which are attributable to divergent corporate drug design strategies, are comparable to the differences between the major drug target classes. On the basis of our analysis, we conclude that a substantial sector of the pharmaceutical industry has not modified its drug design practices and is still producing compounds with suboptimal physicochemical profiles.


Acute effects of hip and knee positions on motor-evoked potentials of the sciatic nerve in total hip arthroplasty.
In 23 patients, motor-evoked potentials (MEP) of the sciatic nerve were elicited during total hip arthroplasty by using a stimulating electrode at the level of the acetabulum and recording from the middle portion of the tibialis anterior. The distal motor latencies were determined before dislocation (control), during dislocation, and after reduction with the trial prosthesis. While the hip was dislocated, recording was performed at varying angles of the hip and knee joints. During dislocation, the distal motor latencies were significantly increased in all positions except at hip flexion of 60 degrees and internal rotation of 60 degrees with the knee joint in maximum flexion. No significant correlations were found between the latency increase and limb lengthening. No patient had sciatic nerve palsy or causalgia after operation.


CK-MM PGAM-MM G6PD and am biochemical markers of functional innervated cultured human muscle fibers.
The biochemical analyses of the total enzymatic activities of CK. PGAM in innervated cultures with advanced morphological maturation showed a progressive increase up to 60 days after innervation, fetal isozyme patterns of CK-BB and PGAM-BB at early stage of innervation and almost complete transition of CK and PGAM from BB to MM isozymes in more advanced stage of innervation (Figs 1, 2). Time course of G6PD activity in parallel cultures showed a higher activity in early stages of myogenesis(myoblastmyotube: 121.4+/-10 nM/min/mg prot) and in early phase of innervation (30 days after innervation: 109.66+/-26.10 nM/min/mg prot) with a decline of activity in advanced stage of innervation (60 days after innervation: 82.33+/-36.55 nM/min/mg prot) A progressive increase of AM activity in mid (30 days after innervation: 1623.66+/-10.96 pM/min/mg prot) and late stage of innervation (45 days after innervation: 2150.33+/-568.27 pM/min/mg prot) in comparison with aneural (536+/-107.39 pM/min/mg prot) was also found our study suggests these enzymes as biochemical markers of functional innervation of cultured human muscle fibers.


Characterization of a putative oomycete taurocyamine kinase: Implications for the evolution of the phosphagen kinase family.
Phosphagen kinases (PKs) are known to be distributed throughout the animal kingdom, but have recently been discovered in some protozoan and bacterial species. Within animal species, these enzymes play a critical role in energy homeostasis by catalyzing the reversible transfer of a high-energy phosphoryl group from Mg⋅ATP to an acceptor molecule containing a guanidinium group. In this work, a putative PK gene was identified in the oomycete Phytophthora sojae that was predicted, based on sequence homology, to encode a multimeric hypotaurocyamine kinase. The recombinant P. sojae enzyme was purified and shown to catalyze taurocyamine phosphorylation efficiently (kcat/KM (taurocyamine) = 2 × 10(5) M(-1) s(-1)) and glycocyamine phosphorylation only weakly (kcat/KM (glycocyamine) = 2 × 10(2) M(-1) s(-1)), but lacked any observable kinase activity with the more ubiquitous guanidinium substrates, creatine or arginine. Additionally, the enzyme was observed to be dimeric but lacked cooperativity between the subunits in forming a transition state analog complex. These results suggest that protozoan PKs may exhibit more diversity in substrate specificity than was previously thought.


Tuning SnO2 architectures with unitary or composite microstructure for the application of gas sensors.
Different SnO2 architectures with unitary or binary structure were successfully assembled utilizing the assistance of Polyvinyl pyrrolidone (PVP). The microstructure, surface topography, specific surface area and gas sensing property were investigated with X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), Brunauer-Emmett-Teller (BET) and WS-60A gas sensing apparatus, respectively. The sensing amplitude, selectivity, response time and recovery time were carefully studied. The possible mechanism of crystallization and gas sensing behavior were also discussed. The present study could be potentially applied to the ethanol or acetone detection and referenced by other researchers and engineers.


Effects of vitamin E on lead-induced impairments in hippocampal synaptic plasticity.
Lead (Pb) exposure during development is associated with impaired cognitive function and long-term potentiation (LTP). Vitamin E (VE) is an antioxidant that could have protective effects against Pb intoxication. In this study, we examined the protective effects of vitamin E against Pb-induced LTP impairments. Forty-six adult male Wistar rats were randomly divided into 6 treatment groups: (1) control; (2) Pb exposure; (3) VE; (4) Pb +VE; (5) Pb exposure followed by VE 2 months after exposure; (6) VE followed by Pb exposure 1 month after treatment. Rats were exposed to Pb through daily consumption of Pb-contaminated distilled water; VE was administered by daily gavage for 3 months. After this period, the population spike (PS) amplitudes and the slopes of excitatory postsynaptic potentials (EPSPs) were measured in the dentate gyrus (DG) area of the hippocampus in adult rats in response to electrical stimulation applied to the perforant pathway in vivo. Blood samples were also collected to evaluate malondialdehyde (MDA) levels, total antioxidant capacity (TAC), and total oxidant status (TOS). Biochemical analyses demonstrated significant increases in plasma MDA and TOS levels in the Pb-exposed group compared to the control group. VE-protected groups revealed significant increases in TAC levels. Our results demonstrate that Pb decreased EPSP slopes and PS amplitudes compared to the control group, whereas VE increased these parameters compared to the control group. Co-administration of VE with Pb exposure inhibited Pb-induced effects. These findings suggest that VE via its antioxidant activity reverses Pb-induced impairments of synaptic plasticity in the DG.


Utilisation of Carp Skin Post-Production Waste in Binary Films Based on Furcellaran and Chitosan to Obtain Packaging Materials for Storing Blueberries.
The aim of the study was to develop and characterise an innovative three-component biopolymer film based on chitosan (CHIT), furcellaran (FUR) and a gelatin hydrolysate from carp skins (Cyprinus carpio) (HGEL). The structure and morphology were characterised using the Fourier transform infrared spectroscopy (FT-IR) and atomic force microscopy (AFM). The FT-IR test showed no changes in the matrix after the addition of HGEL, which indicates that the film components were compatible. Based on the obtained AFM results, it was found that the addition of HGEL caused the formation of grooves and cracks on the surface of the film (reduction by ~21%). The addition of HGEL improved the antioxidant activity of the film (improvement by up to 2.318% and 444% of DPPH and FRAP power, respectively). Due to their properties, the tested films were used as active materials in the preservation of American blueberries. In the active films, the blueberries lost mass quickly compared to the synthetic film and were characterised by higher phenol content. The results obtained in this study create the opportunity to use the designed CHIT-FUR films in developing biodegradable packaging materials for food protection, but it is necessary to test their effectiveness on other food products.


A Little Bit of Cancer is Still Cancer: Is it Time for Lymph Node Micrometastases in Non-small Cell Lung Cancer to Get Their Due?


Atypically slow processing of faces and non-faces in older autistic adults.
Some theories suggested that social difficulties in autism arise from differences in the processing of faces. If face-processing difficulties are central to autism, then they should be as persistent as social difficulties across the lifespan. We tested this by asking autistic and neurotypical participants between 30 and 75 years to complete face detection tasks. Both autistic and neurotypical adults responded more slowly with age. When participants had to respond quickly, autistic adults made more errors in face detection regardless of their age. However, when the time constraint was removed, autistic adults performed as well as the neurotypical group. Across tasks, autistic adults responded more slowly when asked to detect both face and non-face stimuli. We also investigated brain activation differences in the face detection task with functional magnetic resonance imaging. The results indicated lower activation in the autism group in the left and right superior frontal gyrus. The superior frontal gyrus is not typically implicated in face processing but in more general processing, for example, keeping instructions in mind and following them. Together with the behavioral results, this suggests that there is no specific deficit in face processing in autistic adults between 30 and 75 years. Instead, the results suggest differences in general processing, particularly in the speed of processing. However, this needs to be investigated further with methods that are more sensitive to the timing of brain activation.


PDK1-Dependent Metabolic Reprogramming Dictates Metastatic Potential in Breast Cancer.
Metabolic reprogramming is a hallmark of cellular transformation, yet little is known about metabolic changes that accompany tumor metastasis. Here we show that primary breast cancer cells display extensive metabolic heterogeneity and engage distinct metabolic programs depending on their site of metastasis. Liver-metastatic breast cancer cells exhibit a unique metabolic program compared to bone- or lung-metastatic cells, characterized by increased conversion of glucose-derived pyruvate into lactate and a concomitant reduction in mitochondrial metabolism. Liver-metastatic cells displayed increased HIF-1α activity and expression of the HIF-1α target Pyruvate dehydrogenase kinase-1 (PDK1). Silencing HIF-1α reversed the glycolytic phenotype of liver-metastatic cells, while PDK1 was specifically required for metabolic adaptation to nutrient limitation and hypoxia. Finally, we demonstrate that PDK1 is required for efficient liver metastasis, and its expression is elevated in liver metastases from breast cancer patients. Our data implicate PDK1 as a key regulator of metabolism and metastatic potential in breast cancer.


Findings from an organizational network analysis to support local public health management.
We assessed the feasibility of using organizational network analysis in a local public health organization. The research setting was an urban/suburban county health department with 156 employees. The goal of the research was to study communication and information flow in the department and to assess the technique for public health management. Network data were derived from survey questionnaires. Computational analysis was performed with the Organizational Risk Analyzer. Analysis revealed centralized communication, limited interdependencies, potential knowledge loss through retirement, and possible informational silos. The findings suggested opportunities for more cross program coordination but also suggested the presences of potentially efficient communication paths and potentially beneficial social connectedness. Managers found the findings useful to support decision making. Public health organizations must be effective in an increasingly complex environment. Network analysis can help build public health capacity for complex system management.


Selective recovery of founder genetic diversity in aquacultural broodstocks and captive, endangered fish populations.
Hatchery broodstocks used for genetic conservation or aquaculture may represent their ancestral gene pools rather poorly. This is especially likely when the fish that found a broodstock are close relatives of each other. We re-analysed microsatellite data from a breeding experiment on red sea bream to demonstrate how lost genetic variation might be recovered when gene frequencies have been distorted by consanguineous founders in a hatchery. A minimal-kinship criterion based on a relatedness estimator was used to select subsets of breeders which represented the maximum number of founder lineages (i.e., carried the fewest identical copies of ancestral genes). UPGMA clustering of Nei's genetic distances grouped these selected subsets with the parental gene pool, rather than with the entire, highly 'drifted' offspring generation. The selected subsets also captured much of the expected heterozygosity and allelic diversity of the parental gene pool. Independent pedigree data on the same fish showed that the selected subsets had more contributing parents and more founder equivalents than random subsets of the same size. The estimated mean coancestry was lower in the selected subsets, meaning that inbreeding in subsequent generations would be lower if they were used as breeders. The procedure appears suitable for reducing the genetic distortion due to consanguineous and over-represented founders of a hatchery gene pool.


A placebo-controlled, double-blind, crossover trial on analgesic effect of nitrous oxide-oxygen inhalation.
The sedative effect of nitrous oxide-oxygen (N2 O/O2 ) inhalation is relatively well established. Less in known about its analgesic effect. To determine the analgesic effect of N2 O/O2 inhalation on pulp sensitivity and jaw muscle pressure pain threshold in children. A placebo-controlled, double-blind, crossover trial with random allocation to two sequences: atmospheric air at the first session and N2 O/O2 at the second; or N2 O/O2 at the first session and atmospheric air at the second. Measurements included reaction time, pulp pain sensitivity, jaw muscle pressure pain thresholds and a VAS score of overall discomfort from the pain tests. Fifty-six children (12-15 years) completed the study. N2 O/O2 inhalation increased reaction time (P < 0.001). Pulp pain sensitivity was reduced during N2 O/O2 inhalation (P < 0.001), but no effect was found after adjustment for the increased reaction time. Pressure pain threshold on the jaw muscle was also reduced during N2 O/O2 inhalation (P < 0.001), also after adjustment for reaction time (P < 0.005). An effect was still found 10 min after the mask had been removed (P = 0.03). No effect on VAS scores of discomfort from the tests could be found. No analgesic effect of N2 O/O2 inhalation on pulp pain sensitivity was found, whereas an increased pressure pain threshold of jaw muscles was found.


[Morphological and biochemical examinations of different suture materials in colon anastomosis in the rat].
Histological, mechanical and biochemical examinations in the one layer colon anastomosis of the rat have shown that the synthetic resorbable suture material as Dexon and Vicryl are as good or even better than silk or catgut chromic. The most favourable histological reaction is observed with Dexon. Collagenolytic activity and collagen content are not influenced by the suture material during the first 14 postoperative days.


Investigation of human sexual response using a cassette recorder.
A cassette recorder (Medilog miniature analogue tape recorder) initially developed for prolonged recording of ECG and EEG has been adapted for monitoring physiological change during sexual response. The recorder is small, portable, and reliable. Recording can be done by the subject in private. By avoiding the problem of invasion of privacy, it may prove practical to obtain data from patients when information about their ability to cope with the stress of sex response is neeeded for medical counseling. Additionally, a larger population than would ordinarily be available for sex research may become available for study. Tracings from a recording of EEG, ECG, and vaginal photoplethysmography during sex response are presented.


Accountability for quality in managed care.
It is often difficult to understand where responsibility lies for monitoring and improving quality in managed care. From 1996 through 1998 a group of individuals convened by the Institute of Medicine's (Washington, DC) National Roundtable on Health Care Quality developed a model of accountability for the quality of care provided by managed care organizations (MCOs). Each of three overarching forms of accountability (professional, market, and regulatory) has a set of tools for imposing accountability and-because accountability relationships are not self-enforcing-sanctions for failures of accountability. Fiduciary relationships in medicine are an essential part of any quality accountability mechanism, and it will be important to maintain the strength of the professional model in the changing health care system. Yet it is not easy to preserve the strength of the professional model in an MCO environment in which professionals are not dominant, and there is likely to be increasing pressure to weaken their autonomy. The primary assumption of market accountability is that consumers will select options based on perceived value to them and will make new choices based on their information and experience. Market accountability requires choice among competing providers and information to inform choice. In health care, however, individuals rarely have the information they need and often do not have choice. Accountability for quality generally has not been a major feature in contracts. There is a widespread perception of defects in a market-based health care system. Many believe there is a need for a regulatory structure to correct market failures. The use of regulation to impose accountability for quality requires that a regulatory framework, penalties for violations, and effective enforcement mechanisms are all established. PUBLIC GOODS: The model of accountability for quality in managed care does not promote public goods such as education, research, public health, or care for the uninsured. Indeed, the locus of responsibility to the community when markets fail to supply these public goods is controversial. Nevertheless, such responsibility should be considered by MCOs and policy makers. Given market-driven models of health care financing and delivery, it might be feasible and desirable to encourage collaboration among MCOs to improve quality, whether at the national or local market level. The health professions in general, and the medical profession in particular, are and must be accountable to society for providing leadership in the development of knowledge about effective medical care, in defining high-quality care, and in advocating for and improving the quality of care. Establishing effective accountability for quality involves multiple entities and many different kinds of accountability relationships. The three forms of accountability interact, and all operate at once.


Relationships between preclinical course grades and standardized exam performance.
Success in residency matching is largely contingent upon standardized exam scores. Identifying predictors of standardized exam performance could promote primary intervention and lead to design insights for preclinical courses. We hypothesized that clinically relevant courses with an emphasis on higher-order cognitive understanding are most strongly associated with performance on United States Medical Licensing Examination Step exams and National Board of Medical Examiners clinical subject exams. Academic data from students between 2007 and 2012 were collected. Preclinical course scores and standardized exam scores were used for statistical modeling with multiple linear regression. Preclinical courses were categorized as having either a basic science or a clinical knowledge focus. Medical College Admissions Test scores were included as an additional predictive variable. The study sample comprised 795 graduating medical students. Median score on Step 1 was 234 (interquartile range 219-245.5), and 10.2 % (81/795) scored lower than one standard deviation below the national average (205). Pathology course score was the strongest predictor of performance on all clinical subject exams and Step exams, outperforming the Medical College Admissions Test in strength of association. Using Pathology score <75 as a screening metric for Step 1 score <205 results in sensitivity and specificity of 37 and 97 %, respectively, and a likelihood ratio of 11.9. Performance in Pathology, a clinically relevant course with case-based learning, is significantly related to subsequent performance on standardized exams. Multiple linear regression is useful for identifying courses that have potential as risk stratifiers.


The course of olfactory deficits in patients with Parkinson's disease--a study based on psychophysical and electrophysiological measures.
Patients with Parkinson's disease (PD) commonly show olfactory deficits in the early stages of the disease. These deficits can be verified psychophysically or electrophysiologically using olfactory event-related potentials (OERP). While psychophysical olfactory function in PD patients can improve over time, the course of OERPs in PD has not yet been investigated. Olfactory function was investigated twice in 19 patients at 5-year intervals. Psychophysical tests included the "Sniffin' Sticks" test battery. In addition, OERPs were recorded in response to two odors on each side (phenyl-ethyl-alcohol: 40% (v/v), H(2)S, 6ppm). OERPs were evaluated regarding existence (yes/no). Average disease duration at follow-up was 9.0 years and the average Hoehn and Yahr score (disease stage) was 2.2. Psychophysically, 1 patient was normosmic, 14 were hyposmic, and 4 were functionally anosmic at the initial visit. Re-examination revealed 1 normosmic, 9 hyposmic, and 8 functionally anosmic patients. Mean olfactory function decreased significantly in all patients. OERPs were initially existent in 3 out of 19 patients. At follow-up, OERPs were no longer present in these patients, but were detectable in 3 other patients. Overall, mean olfactory function decreased, although improvements were observed at the individual level. We confirmed previous findings regarding psychophysical follow-up results. Electrophysiological measures showed a pattern of fluctuation in olfactory function comparable to that of the psychophysical results. These fluctuations do not seem to predict the course of the disease.


Methodological Development and Applications of Tryptamine-Ynamide Cyclizations in Synthesizing Core Skeletons of Indole Alkaloids.
Over the past two decades, synthetic strategies for synthesizing the skeletons of various indole alkaloids based on tryptamine-ynamide have been continuously developed and applied to the total syntheses or formal total syntheses of related molecules. In this synopsis, we summarized the cyclization pathways of tryptamine-ynamide under different catalytic conditions, emphasizing the reaction mechanism and applications in the syntheses of indole alkaloids.


Predicted reduction in transmission from deployment of ivermectin-treated birdfeeders for local control of West Nile virus.
Ivermectin (IVM)-treated birds provide the potential for targeted control of Culex mosquitoes to reduce West Nile virus (WNV) transmission. Ingestion of IVM increases mosquito mortality, which could reduce WNV transmission from birds to humans and in enzootic maintenance cycles affecting predominantly bird-feeding mosquitoes and from birds to humans. This strategy might also provide an alternative method for WNV control that is less hampered by insecticide resistance and the logistics of large-scale pesticide applications. Through a combination of field studies and modeling, we assessed the feasibility and impact of deploying IVM-treated birdfeed in residential neighborhoods to reduce WNV transmission. We first tracked 105 birds using radio telemetry and radio frequency identification to monitor their feeder usage and locations of nocturnal roosts in relation to five feeder sites in a neighborhood in Fort Collins, Colorado. Using these results, we then modified a compartmental model of WNV transmission to account for the impact of IVM on mosquito mortality and spatial movement of birds and mosquitoes on the neighborhood level. We found that, while the number of treated lots in a neighborhood strongly influenced the total transmission potential, the arrangement of treated lots in a neighborhood had little effect. Increasing the proportion of treated birds, regardless of the WNV competency status, resulted in a larger reduction in infection dynamics than only treating competent birds. Taken together, model results indicate that deployment of IVM-treated feeders could reduce local transmission throughout the WNV season, including reducing the enzootic transmission prior to the onset of human infections, with high spatial coverage and rates of IVM-induced mortality in mosquitoes. To improve predictions, more work is needed to refine estimates of daily mosquito movement in urban areas and rates of IVM-induced mortality. Our results can guide future field trials of this control strategy.


Revision INBONE total ankle replacement.
The INBONE total ankle replacement is a unique modular ankle replacement that has the ability to serve as both a primary and a revision total ankle replacement. Despite its versatility, it may need to be revised, either because of poor patient selection, technical error, or infection. This article may be of value to those surgeons embarking on the primary placement or revision of an INBONE total ankle replacement.


Arthrography of the shoulder in anterior dislocation: a study of African and Asian patients.
Arthrography of the shoulder was performed in 16 consecutive cases of primary anterior dislocation and in 11 cases of recurrent dislocation. All the primary dislocations were in African Negro patients and showed an unusually high incidence of capsular rupture rather than labral detachment. It is suggested that this is due to stronger soft tissue attachment to bone in Africans, resulting in fewer labral detachments and thus accounting for the low incidence of recurrent dislocation in the African populace. The series of recurrent dislocations, consisting of African and Asian patients, confirmed the low incidence in Africans but demonstrated labral detachment and humeral head defects common to both racial groups.


Habitual physical activity and peripheral arterial compliance in young adults: the Amsterdam growth and health longitudinal study.
It remains unclear whether the impact of habitual physical activity (HPA) differs for central vs. peripheral arterial stiffness, both of which are detrimental to cardiovascular health. We investigated the associations of lifetime HPA of different intensities on brachial and femoral stiffness in young adults, and compared these with those previously obtained for the carotid artery in the same study population. Prospectively measured data (eight repeated measures between ages 13 and 36 years) on HPAs, and other lifestyle and biological variables, were retrieved for 373 subjects in whom stiffness of the brachial and femoral, as well as the carotid, arteries was assessed at age 36 years. Generalized estimating equations were used to examine the differences in time spent in HPAs (min/week) across sex-specific tertiles of the brachial and femoral distensibility (DC) and compliance (CC) coefficients. After adjustment for potential confounders, subjects in the highest (more compliant) vs. those in the lowest tertiles of the brachial and femoral CCs (less compliant) at age 36 years had spent on average more time in vigorous (+21.2 (95%CI:2.0; 40.4) and +24.4 (5.0; 43.8), respectively) but not in light-to-moderate HPAs throughout the longitudinal period. These differences were explained by 28 and 62%, respectively, by vigorous-HPA-related favorable impacts on other cardiovascular risk factors. No such associations were observed for the brachial and femoral DCs, however. Lifetime vigorous, but not light-to-moderate, HPA is favorably associated with brachial and femoral compliance, but not DC. Altogether, these and our previous findings thus suggest generalized vigorous-HPA-related adaptations, although of different nature, throughout the arterial tree.


Otologic manifestations of Larsen syndrome.
To describe and discuss otologic manifestations of Larsen syndrome, based on a case report and a systematic review of the literature. We performed a PubMED database search, and we selected studies reporting otolaryngologic manifestations secondary to Larsen syndrome. The selected articles were read in full, and three researchers independently extracted data from the studies. In parallel, we report the case of a 14-year-old patient who had hearing loss secondary to Larsen syndrome. Fifteen studies met our selection criteria. Seven studies reported hearing loss in patients with Larsen syndrome (4 had conductive hearing loss and 3 had mixed hearing loss). The conductive hearing loss may be secondary to ossicular malformations and/or middle ear effusions. Other causes for conductive hearing loss are mesenchymal remnants in the middle ear, Eustachian tube dysfunction, and cleft palate. Surgical management of the hearing loss is possible in selected cases, although the surgical and anesthetic risks should be considered. Hearing aids seem to be safe and effective treatment options for the hearing loss secondary to Larsen syndrome. Although rare, patients with Larsen syndrome may have hearing loss. The most frequent type of deficit is conductive, either secondary to malformation of the ossicles or middle ear effusion. Possible surgical correction of these abnormalities should be weighed against the anesthetic risks of these patients.


Rapid displacement chromatography of melittin on micropellicular octadecyl-silica.
Rapid high-performance liquid chromatographic analysis and displacement purification of melittin and its variants were carried out by reversed-phase chromatography. High speed of separation was achieved by the use of columns packed with a micropellicular stationary phase consisting of a thin C18 hydrocarbonaceous layer on the surface of 2-microns fluid-impervious silica microspheres at elevated temperature. In the case of melittin from bee venom or its synthetic variants the plots of the logarithmic retention factor against acetonitrile concentration in the eluent were straight lines whereas the van't Hoff plots in the temperature range from 20 to 80 degrees C were non-linear. Purification of melittins by displacement was carried out with benzyldimethylhexadecyl ammonium chloride as the displacer. In a 20-min displacement run at 40 degrees C about 5 mg of highly pure melittin were isolated from 10 mg of synthetic mixture by using a 105 x 4.6 mm column. The results demonstrate that columns packed with micropellicular sorbents not only facilitate rapid high-performance liquid chromatographic analysis but are also suitable for fast peptide purification with high recovery.


Development of an exercise testing protocol for patients with a lower limb amputation: results of a pilot study.
Due to a decrease in physical activity, lower limb amputees experience a decline in physical fitness. This causes problems in walking with a prosthesis because energy expenditure in walking with a prosthesis is much higher than in walking with two sound legs. Exercise training may therefore increase the functional walking ability of these patients. To generate a safe and effective aerobic training program, exercise testing of amputees is recommended. The objectives of this study were to develop a maximal exercise testing protocol for lower limb amputees and to compare two different testing methods: combined arm-leg ergometry and arm ergometry. The protocols were tested in five amputee patients. Combined ergometry elicited a higher oxygen uptake and heart rate than arm ergometry. Electrocardiography during combined ergometry was easier to read. Combined ergometry was judged most comfortable by the amputees. The exercise testing protocol was useful in lower limb amputees to determine their maximal aerobic capacity and their main exercise limitation. Future exercise training programs may be based on this testing protocol. Combined arm-leg ergometry is appropriate for unilateral amputees without significant claudication of the remaining leg. Continuous arm ergometry is suitable for unilateral amputees with significant claudication of the remaining limb or bilateral amputees.


Hyperspectral field spectroscopy and SENTINEL-2 Multispectral data for minerals with high pollution potential content estimation and mapping.
Mining in Tunisia generates a large amount of tailings charged with toxic minerals. As these tailings have a wide spread distribution, it is important to characterize and estimate their impact on soil contamination. This study examines the potential of field hyperspectral spectroscopy and SENTINEL-2 Multispectral data in estimating and mapping seven minerals content, including three toxic minerals (fluorite, barite and sphalerite), within soils around Hammam Zriba mine in Northen Tunisia. 69 soil and dike surface samples were collected, field Visible, Near InfraRed (VNIR) and Short-Wave InfraRed (SWIR) reflectance spectra were measured on these surfaces. The X-ray diffraction (XRD) method was used to identify the types of mineral and their associated contents on each collected soil samples. The mineral contents were predicted using the partial least squares regression (PLSR) method using i) field VNIR-SWIR spectra at raw spectral resolution, ii) field VNIR-SWIR spectra aggregated to the SENTINEL-2 spectral resolution and then iii) SENTINEL-2 spectra. This study shows 1) an accurate prediction of four of the seven minerals using field VNIR-SWIR spectroscopy, 2) a slight decrease of performances due to spectral resolution degradation (SENTINEL-2 simulated spectra) and 3) a significant decrease of performances due to spatial resolution degradation, except for fluorite. This work paves the way for large-scale mapping of minerals with high pollution potential using SENTINEL-2 data. In addition, the high frequency of SENTINEL-2 data may be used to monitor the spatial distribution of some minerals with high pollution potential in soils.


Feeding of tropical freshwater fishes: seasonality in resource availability and resource use.
Food resources in the environment and in the diets of small fish inhabiting two water bodies in a tropical savanna were studied during both wet and dry seasons. During the wet season (high water, abundant food) most fish species in both habitats fed predominantly on vegetation-dwelling invertebrates. Most fish species switched to alternative foods (algae and detritus) following the drastic decline in invertebrate food available towards the end of the dry season. In one habitat, this change in diet was accompanied by an increase in the volume of food intake. In the second habitat, only two larger species foraged intensively, while smaller species showed low food intake or almost ceased feeding. These differences may be explained by the high risk of predation for small fish in the second habitat. Dietary overlaps among fish species were high at the end of the dry season and moderate in the wet season. However, critical analysis of such factors as food abundance, the size and number of shared prey, and diet breadth showed that all significant overlaps were ecologically unimportant i.e. there was only weak competition for food.


Visualization of Mitochondrial RNA Granules in Cultured Cells Using 5-Bromouridine Labeling.
The incorporation of nucleoside analogs is a useful tool to study the various functions of DNA and RNA. These analogs can be detected directly by fluorescence or by immunolabeling, allowing to visualize, track, or measure the nucleic acid molecules in which they have been incorporated. In this chapter, methodologies to measure human mitochondrial transcription are described. The nascent RNA that is transcribed from mitochondrial DNA (mtDNA) has been shown to assemble into large ribonucleoprotein complexes that form discrete foci. These structures were called mitochondrial RNA granules (MRGs) and can be observed in vitro by the incorporation of a 5-Bromouridine (BrU), which is subsequently visualized by fluorescent immunolabeling. Here, a combined protocol for the MRGs detection is detailed, consisting of BrU labeling and visualization of one of their bona fide protein components, Fas-activated serine-threonine kinase domain 2 (FASTKD2). Based on immunodetection, the half-life and kinetics of the MRGs under various experimental conditions can further be determined by chasing the BrU pulse with an excess of Uridine.


Xanthines as adenosine receptor antagonists.
The natural plant alkaloids caffeine and theophylline were the first adenosine receptor (AR) antagonists described in the literature. They exhibit micromolar affinities and are non-selective. A large number of derivatives and analogues were subsequently synthesized and evaluated as AR antagonists. Very potent antagonists have thus been developed with selectivity for each of the four AR subtypes.


Skin penetration of infective hookworm larvae. I. The path of migration of infective larvae of Ancylostoma braziliense in canine skin.
Migratory behaviour of Ancylostoma braziliense was studied in relation to the structure of the skin in dogs after primary infections. Data were obtained studying serial sections of lateral skin areas 6 mm in diameter, which had been exposed to larvae. The sections were stained either with Harris' haematoxylin and eosin or with P.A.S. or as outlined by Crossmon. Most of the larvae managed to penetrate the skin within 1/2 hr after the application. Hairs did not seem to constitute sites of entry. The larvae moved into the horny layer where edges of keratinized cells provide uneven spots. They migrated approximately parallel to the surface from the horny layer into the living epidermis and continued into an external root sheath of a hair follicle. They could only leave this site via sebaceous glands for the dermis or via apocrine sweat glands for the hypodermis. Tunnels from the epidermis into the dermis, however, suggested that a direct trans-epidermal migration had occurred. The vessels invaded by larvae were hypodermal lymphatic vessels. The first ones were found in these structures 1/2 h after the onset of the exposure.


New immunoassays for total, IgA and IgM antibodies against hepatitis E virus: Prevalence in Italian blood donors and patients with chronic liver or kidney diseases.
Hepatitis E virus (HEV) is a zoonotic agent that causes acute hepatitis in humans with sporadic infections and outbreaks in developing countries worldwide. The global spread of HEV remains underestimated because of subclinical infections and lack of sensitive diagnostic assays. To study the prevalence of HEV antibodies (anti-HEV) in sera of blood-donors and patients with chronic-liver-disease and chronic-renal-disease, using newly developed anti-HEV assays. 396 sera from 199 blood-donors, 109 chronic-liver-disease patients and 88 chronic-renal-disease patients and three standard reference serum panels were tested in parallel with a sensitive reference anti-HEV assay and newly developed assays for IgA, IgM and total anti-HEV based on HEV-like-particles produced by recombinant baculo-viruses. Overall, total anti-HEV was detected in 12.9% (7.0% blood-donors, 9.2% and 30.7% chronic-liver-disease patients and chronic-renal-disease patients, respectively). We observed a higher anti-HEV prevalence in older subjects and in chronic-renal-disease patients in relation with degree on immune-depression (p<0.001). Results from reference serum panels showed an optimal and slightly better performance of the new assay over the commercially available assay. Newly developed anti-HEV assays using recombinant HEV-like-particles showed optimal diagnostic performances assessing that HEV-infection is endemic in Italy with seroprevalence ranging from 7% to 30% in blood donors and immune-compromised hosts, respectively.


Genome characterization of the novel lytic genome sequence of the phage YUEEL01 of the Myoviridae family.
Antimicrobial resistance is a global concern because of its rapid emergence in the environment and the associated high risk to human and animal health. Municipal wastewater, including urban, hospital, and pharmaceutical effluent, is the primary source of contamination by antibiotics and antibiotic-resistant bacteria (ARB). Biological processes are commonly used for wastewater treatment. Biologically based strategies are a promising approach to effective integrated ARB control because they focus on antibiotic resistance. An effective bacteriophage against multi-drug resistance (MDR) microbes in municipal wastewater was.


Relative gas-liquid chromatographic retention factors of trimethylsilyl ethers of diradylglycerols on polar capillary columns.
Gas-liquid chromatography (GLC) on polar capillary columns provides a highly reproducible resolution and quantitation of molecular species of diradylglycerols when analyzed as the trimethylsilyl (TMS) ethers. In the absence of peak collection and determination of fatty acids or mass spectrometry, peak identification is obtained on the basis of relative retention times of reference standards or of relative retention times calculated from the additive contributions of component fatty chains. Unlike simple esters, complex mixtures of diradylglycerols present special problems in GLC peak identification, which must be attended to by auxiliary separations prior to GLC analysis. In the present study the positional sn-1,2(2,3)- and X-1,3-isomers were resolved by borate thin-layer chromatography (TLC) while the alkenylacyl-, alkylacyl- and diacylglycerols were separated as their TMS ethers by normal-phase high-performance liquid chromatography. The diradylglycerol nature of the sample was further verified by GLC determination of the carbon number distribution, which must be consistent with the composition of the fatty chains of the sample. Under these conditions the identification and quantitation of the molecular species on the polar capillary columns was always consistent with the total fatty acid composition of the sample, as well as with the fatty acid composition of any argentation TLC fractions isolated from some of the samples prior to the polar capillary GLC. Due to the great complexity of the natural diradylglycerol mixtures some peak overlaps occurred, which were reflected in their relative retention times. Nevertheless, a determination of diradylglycerol peak identity from relative retention times proved very satisfactory provided the above described procedures were employed.


Multivariate analysis of urinary RNA catabolites in malignancies: cross-sectional and longitudinal studies.
Urinary RNA catabolites, especially modified nucleosides and nucleobases, have turned out to represent valuable new criteria for diagnosis and follow-up of malignancies. Here we show for the first time that multivariate analysis of urinary RNA catabolites can distinguish between tumor carriers and controls who, if examined by univariate procedures, would remain undifferentiated. Two such models have been demonstrated. We hope that a continuation of this work will support primary clinical diagnostic procedures, the control of therapy effects, and the long-term follow-up of patients, which should be regarded as special medical applications of the general principles of molecular biology.


Myo-inositol in physiological concentrations stimulates production of prostaglandin-like material.
In physiological concentrations myo-inositol stimulated production of prostaglandin (PG)-like material in a rat mesenteric vascular bed preparation. There were five lines of evidence: 1. Inositol potentiated pressor responses to both norepinephrine and potassium in a manner similar to PGE2. 2. Inositol had no potentiating effect in preparations in which endogenous PG production was blocked by indomethacin. 3. Inositol caused no further potentiation in preparations already potentiated by arachidonic acid, the PG precursor. 4. The inhibitory effect of the PG antagonist chloroquine was reduced in an apparently competitive manner by inositol. 5. As indicated by rat stomach bioassay inositol caused a three fold rise in the outflow of PG-like material from the preparation.


Dietary bovine milk miRNAs transported in extracellular vesicles are partially stable during GI digestion, are bioavailable and reach target tissues but need a minimum dose to impact on gene expression.
Extracellular RNAs are unstable and rapidly degraded unless protected. Bovine-milk extracellular vesicles (EVs) confer protection to dietary miRNAs, although it remains unclear whether this importantly improves their chances of reaching host target cells to exert biological effects. Caco-2, HT-29, Hep-G2 and FHs-74 cell lines were exposed to natural/labelled milk EVs to evaluate cellular uptake. Five frequently reported human milk miRNAs (miR-146b-5p, miR-148a-3p, miR-30a-5p, miR-26a-5p, and miR-22-3p) were loaded into EVs. The intracellular concentration of each miRNA in cells was determined. In addition, an animal study giving an oral dose of loaded EVs in C57BL6/ mice were performed. Gene expression regulation was assessed by microarray analysis. Digestive stability analysis showed high overall degradation of exogenous miRNAs, although EV-protected miRNAs better resisted gastrointestinal digestion compared to free miRNAs (tenfold higher levels). Importantly, orally delivered EV-loaded miRNAs reached host organs, including brain, in mice. However, no biological effect has been identified. Milk EVs protect miRNAs from degradation and facilitate cellular uptake. miRNA concentration in EVs from bovine milk might be insufficient to produce gene modulation. Nevertheless, sizable amounts of exogenous miRNAs may be loaded into EVs, and orally delivered EV-loaded miRNAs can reach tissues in vivo, increasing the possibility of exerting biological effects. Further investigation is justified as this could have an impact in the field of nutrition and health (i.e., infant formulas elaboration).