[Characteristics of the response of rabbit visual cortex neurons to intracortical electric stimulation].
Responses of visual cortex neurons to single and rhythmical intracortical electrical stimulation were investigated in rabbits. Stimulating and recording electrodes were separated by 0.7-1.2 mm. Thresholds of responses to single stimuli were in general about 150-180 microA, to serial stimuli -- 30-60 microA. Latency of the first spike was 5-15 ms, but probability of discharge was very low (3-6%). The length of the inhibitory phrase in the response increased in a half of the investigated neurons with the increase in the stimulus strength. Spontaneous activity after a series of stimuli increased during 4-6 s. Repeated single stimuli induced in about a half of the investigated neurons the same types of dynamic modifications in activity, as those produced by light stimulation. However, in response to electrical stimulation more neurons developed discharge sensitization and less habituation. It is supposed that intracortical stimulation induces in the visual cortex excitation of local hypercolumns and inhibition of the neighbouring ones.


Protein 1 (Clara cell protein) serum levels in lung cancer patients receiving chemotherapy.
As many antineoplastic drugs can cause injury to alveolar pneumocytes, Clara cells (nonciliated, nonmucous epithelial cells of the bronchioles) may also be damaged by such drugs. Protein 1 (P1) is an alpha-microprotein secreted by Clara cells. The effect of antineoplastic drugs on Clara cells is examined by the measurement of serum levels of P1 in patients with lung cancer receiving chemotherapy. Serum levels of P1 were studied in 36 patients with lung cancer, before chemotherapy and 5-7, 10-12 and 14-18 days after chemotherapy. One hundred and eight healthy subjects, matched by sex and age, acted as controls. There was no significant difference in P1 serum levels between patients with lung cancer and healthy controls. P1 serum levels decreased significantly 5-7 and 10-12 days after chemotherapy, recovering thereafter. We conclude that P1 serum levels do not differ between lung cancer patients and healthy controls, and that antineoplastic drugs inhibit the synthesis or secretion of P1 by Clara cells in the early period after the administration of medication.


Augmentation of oxidant injury to human pulmonary epithelial cells by the Pseudomonas aeruginosa siderophore pyochelin.
Pseudomonas aeruginosa causes acute and chronic infections of the human lung, with resultant tissue injury. We have previously shown that iron bound to pyochelin, a siderophore secreted by the organism to acquire iron, is an efficient catalyst for hydroxyl radical (HO.) formation and augments injury to pulmonary artery endothelial cells resulting from their exposure to superoxide (O2.) and/or H2O2. Sources for O2-. and H2O2 included phorbol myristate acetate (PMA)-stimulated neutrophils and pyocyanin. Pyocyanin, another P. aeruginosa secretory product, undergoes cell-mediated redox, thereby forming O2-. and H2O2. In P. aeruginosa lung infections, damage to airway epithelial cells is probably more extensive than that to endothelial cells. Therefore, we examined whether ferripyochelin also augments oxidant-mediated damage to airway epithelial cells. A549 cells, a human type II alveolar epithelial cell line, was exposed to H2O2, PMA-stimulated neutrophils, or pyocyanin, and injury was determined by release of 51Cr from prelabeled cells. Ferripyochelin significantly increased (> 10-fold) oxidant-mediated cell injury regardless of whether H2O2, neutrophils, or pyocyanin was employed. Apo-pyochelin was not effective, and ferripyochelin was not toxic by itself at the concentrations employed. Spin trapping with alpha-(4-pyrridyl-1-oxide)-N-t-butyl-nitrone-ethanol confirmed the generation of HO., and injury was decreased by a variety of antioxidants, including superoxide dismutase, catalase, and dimethylthiourea. These data are consistent with the hypothesis that the presence of ferripyochelin at sites of P. aeruginosa lung infection could contribute to tissue injury through its ability to promote HO.-mediated damage to airway epithelial cells.


Immunofluorescence detection of nitrogenase proteins in whole cells.
Fluorescent antibodies (FA) prepared against the Mo-Fe and Fe proteins of nitrogenase from Klebsiella pneumoniae M5aI were used to detect these protein components in toluene-treated whole cells that were actively reducing acetylene. The FA were highly specific, staining only nitrogenase component proteins originating from Klebsiella. Cross-reactions between the FA and purified nitrogenase proteins from other dinitrogen-fixing micro-organisms did not occur, except in the case of Bacillus polymyxa. The tests rapidly and accurately assayed the component proteins in Klebsiella mutants and derivatives to which Klebsiella nif genes had been transferred either by plasmid or by other means. Cross-reactions also indicated the degree of relatedness between nitrogenase proteins from dinitrogen-fixing micro-organisms of various origins.


Emerging Mosquito-Borne Threats and the Response from European and Eastern Mediterranean Countries.
Mosquito-borne viruses are the cause of some of the greatest burdens to human health worldwide, particularly in tropical regions where both human populations and mosquito numbers are abundant. Due to a combination of anthropogenic change, including the effects on global climate and wildlife migration there is strong evidence that temperate regions are undergoing repeated introduction of mosquito-borne viruses and the re-emergence of viruses that previously were not detected by surveillance. In Europe, the repeated introductions of West Nile and Usutu viruses have been associated with bird migration from Africa, whereas the autochthonous transmission of chikungunya and dengue viruses has been driven by a combination of invasive mosquitoes and rapid transcontinental travel by infected humans. In addition to an increasing number of humans at risk, livestock and wildlife, are also at risk of infection and disease. This in turn can affect international trade and species diversity, respectively. Addressing these challenges requires a range of responses both at national and international level. Increasing the understanding of mosquito-borne transmission of viruses and the development of rapid detection methods and appropriate therapeutics (vaccines / antivirals) all form part of this response. The aim of this review is to consider the range of mosquito-borne viruses that threaten public health in Europe and the eastern Mediterranean, and the national response of a number of countries facing different levels of threat.


Deinstitutionalization and the rise of violence.
The deinstitutionalization of individuals with serious mental illness was driven by 4 factors: public revelations regarding the state of public mental hospitals, the introduction of antipsychotic medications, the introduction of federal programs to fund patients who had been discharged, and civil libertarian lawyers. The result is approximately 3.2 million individuals with untreated serious mental illness living in the community. Beginning in the 1970s in the United States, there began to be reported increasing incidents of violent behavior, including homicides, committed by these untreated individuals. Such incidents became more numerous in the 1980s and 1990s, and have further increased since the turn of the century. Existing studies suggest that individuals with untreated severe mental illness are responsible for at least 10% of all homicides and approximately half of all mass killings. Studies have also shown that when these individuals are treated, the incidence of violent behavior decreases significantly. Examples of treatment mechanisms that have proven effective include assisted outpatient treatment (AOT), conditional release, and mental health courts.


A technique for internal mammary artery to coronary artery anastomoses.
A "no-touch" technique for anastomosing the internal mammary artery to the anterior descending artery is described. This technique has been used in more than 3000 patients, and enables one to construct a long, patulous anastomosis in which all suturing is forehand.


Sex ratios and gender discrimination in Modern Greece.
This paper argues that son preference resulted in gender-based discriminatory practices that unduly increased mortality rates for females at birth and throughout infancy and childhood in nineteenth- and early-twentieth-century Greece. The relative numbers of boys and girls at birth was extremely high and under-registration of females cannot on its own explain this result. The infanticide and/or mortal neglect of infant girls was therefore more common than previously acknowledged. Likewise, sex ratios increased as children grew older, thus suggesting that parents continued to treat boys and girls differently throughout childhood. A large body of qualitative evidence (contemporary accounts, folklore traditions, feminist newspapers, and anthropological studies) further supports the conclusion that girls were neglected due to their inferior status in society.


Cranial ultrasound - optimizing utility in the NICU.
Cranial ultrasonography (cUS) is a reliable tool to detect the most frequently occurring congenital and acquired brain abnormalities in full-term and preterm neonates. Appropriate equipment, including a dedicated ultrasound machine and appropriately sized transducers with special settings for cUS of the newborn brain, and ample experience of the ultrasonographist are required to obtain optimal image quality. When, in addition, supplemental acoustic windows are used whenever indicated and cUS imaging is performed from admission throughout the neonatal period, the majority of the lesions will be diagnosed with information on timing and evolution of brain injury and on ongoing brain maturation. For exact determination of site and extent of lesions, for detection of lesions that (largely or partially) remain beyond the scope of cUS and for depiction of myelination, a single, well timed MRI examination is invaluable in many high risk neonates. However, as cUS enables bedside, serial imaging it should be used as the primary brain imaging modality in high risk neonates.


Clinical comparison of unilateral biportal endoscopic transforaminal lumbar interbody fusion verse 3D microscope-assisted transforaminal lumbar interbody fusion in the treatment of single-segment lumbar spondylolisthesis with lumbar spinal stenosis: a retrospective study with 24-month follow-up.
To explore the safety and the mid-term efficacy of unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) and 3D microscope-assisted transforaminal lumbar interbody fusion (MMIS-TLIF) for treating single-segment lumbar spondylolisthesis with lumbar spinal stenosis (DLS-LSS). The clinical data of 49 patients who underwent UBE-TLIF or MMIS-TLIF in our hospital were retrospectively analyzed, including 26 patients who underwent the UBE-TLIF and 23 patients who underwent the MMIS-TLIF. The demographic and perioperative outcomes of patients before and after surgery were reviewed. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate the clinical outcomes of patients before surgery and at 1, 3, 6, 12 and 24 months after surgery. The lumbar lordosis angle (LL), disc height (DH) and lumbar intervertebral fusion rate were assessed before surgery and at the last follow-up. The VAS and ODI scores of the two groups were improved compared with those before surgery. The ODI of UBE-TLIF group was lower than that of MMIS-TLIF group at 1, 3, 6, and 12 months after surgery, and there were no significant differences between the two groups at other time points (P > 0.05). There were no significant differences in VAS between the two groups at each time point (P > 0.05). However, the UBE-TLIF group had more advantages in blood loss and hospital stay. The complications between the UBE-TLIF group (11.54%) and the MMIS-TLIF group (17.39%) were comparable (P > 0.05). Radiographic outcomes showed that the LL and DH of the two groups were improved compared with those before surgery, and the difference before and after surgery was not significant (P > 0.05). The fusion rate was 96.2% in the UBE-TLIF group and 95.7% in the MMIS-TLIF group. There was no significant difference in the fusion rate between the two groups (P > 0.05). Both UBE-TLIF and MMIS-TLIF have favorable outcomes for treating single-segment DLS-LSS. Both groups have the advantages of clear surgical vision, high surgical efficiency, and favorable mid-term efficacy. In addition, compared with MMIS-TLIF, UBE-TLIF causes less intraoperative bleeding and faster postoperative recovery.


Fast time-domain diffuse optical tomography using pseudorandom bit sequences.
We report a novel time-domain diffuse optical tomography to determine the optical properties in a faster speed than the conventional ones. Instead of using the ultrashort pulse laser, a 2.5 Gbps pseudorandom bit sequence is used to modulate the near-infrared light for tissue-like phantom illumination. The time-resolved signal can be retrieved very quickly by demodulation with the reference signal. The system impulse response has a full width at half maximum around 800 picoseconds and the 2-dimentional maps of optical properties can be obtained within a few seconds. The high signal-to-noise ratio and the environmental illumination insensitivity warrant a great potential for applications in clinical noninvasive breast cancer detection.


NO chemiluminescence in exhaled air: interference of compounds from endogenous or exogenous sources.
Nitric oxide determination in exhaled air using chemiluminescence analysers is increasingly used, but may be affected by various other components of the air sample. The influence of several compounds originating from endogenous or exogenous sources on NO readings has been studied. Defined amounts of water vapour, carbon dioxide, acetone, heptane, acetonitrile, oxygen, nitrous oxide and enflurane were added to air samples with NO concentrations 0-250 parts per billion. Marked and significant decreases in NO readings, which strongly depend on the concentration of the respective interfering compound, were found for water vapour (0.155% per 1% relative humidity), carbon dioxide (1.97% per 1% CO2 volume/volume (v/v)) and nitrous oxide (0.608% per 1% v/v N2O). While acetone in concentrations up to 8.5% v/v had no measurable effect on NO readings, heptane and acetonitrile led to marked decreases. Oxygen in concentrations of up to 95% (v/v) had no effect on NO determination. NO readings were markedly decreased by >10% per 1% (v/v) of the anaesthetic enflurane. However, due to large variations in NO values, these decreases were not statistically significant. Furthermore, enflurane reacted with the molybdenum converter of the NO(x) analyser in use, resulting in major damage to the instrument. Eliminating, or at least considering, interferences by compounds present in exhaled air is an urgent prerequisite for reliable and precise nitric oxide determination.


Aetiological agents of surgical site infection in a specialist hospital in Kano, north-western Nigeria.
Despite the advances made in asepsis, antimicrobial drugs, sterilization and operative techniques, surgical site infections (SSI) continue to be a major problem in all branches of surgery in the hospitals. The objective of this study was to establish the incidence of SSI, the type and frequency of various pathogens and their antibiotic susceptibility pattern in Murtala Mohammed Specialist Hospital (MMSH), Kano, Nigeria. A total of 2,920 consecutive patients who underwent different surgical procedures between January 2009 and December 2010 at Murtala Mohammed Specialist Hospital were enrolled in this study. Samples of pus were collected from infected cases and screened for bacterial and fungal pathogens by standard microbiological methods. Antibiotic susceptibility tests were done by disc diffusion technique. A total 878 patients were found to be clinically infected and 919 isolates were obtained in all. This gave an incidence of 30.1% infection rate. While 783 (89.2%) cultures yielded single organism, 77 (9.8%) yielded mixed growth and 18(8.1%) cultures yielded no growth. The most frequently isolated organism was E. coli (25.5%) followed by Staphylococcus aureus 20.6%. The incidence of Methicillin resistant Staphylococcus aureus was 35.7%. Ceftriaxone, ceftazidime and ofloxacin showed good results against most isolates while ampicillin and cotrimoxazole which are commonly used drugs were ineffective. An understanding of the various types of pathogen involved in SSI and their antibiotic susceptibility pattern will reduce indiscriminate prescription of antibiotics and help in infection control.


Intestinal delta-6-desaturase activity determines host range for Toxoplasma sexual reproduction.
Many eukaryotic microbes have complex life cycles that include both sexual and asexual phases with strict species specificity. Whereas the asexual cycle of the protistan parasite Toxoplasma gondii can occur in any warm-blooded mammal, the sexual cycle is restricted to the feline intestine. The molecular determinants that identify cats as the definitive host for T. gondii are unknown. Here, we defined the mechanism of species specificity for T. gondii sexual development and break the species barrier to allow the sexual cycle to occur in mice. We determined that T. gondii sexual development occurs when cultured feline intestinal epithelial cells are supplemented with linoleic acid. Felines are the only mammals that lack delta-6-desaturase activity in their intestines, which is required for linoleic acid metabolism, resulting in systemic excess of linoleic acid. We found that inhibition of murine delta-6-desaturase and supplementation of their diet with linoleic acid allowed T. gondii sexual development in mice. This mechanism of species specificity is the first defined for a parasite sexual cycle. This work highlights how host diet and metabolism shape coevolution with microbes. The key to unlocking the species boundaries for other eukaryotic microbes may also rely on the lipid composition of their environments as we see increasing evidence for the importance of host lipid metabolism during parasitic lifecycles. Pregnant women are advised against handling cat litter, as maternal infection with T. gondii can be transmitted to the fetus with potentially lethal outcomes. Knowing the molecular components that create a conducive environment for T. gondii sexual reproduction will allow for development of therapeutics that prevent shedding of T. gondii parasites. Finally, given the current reliance on companion animals to study T. gondii sexual development, this work will allow the T. gondii field to use of alternative models in future studies.


Effects of oxidative stress on phospholipid signaling in rat cultured astrocytes and brain slices.
Although reactive oxygen species (ROS) are conventionally viewed as toxic by-products of cellular metabolism, a growing body of evidence suggests that they may act as signaling molecules. We have studied the effects of hydrogen peroxide (H(2)O(2))-induced oxidative stress on phospholipid signaling in cultured rat cortical astrocytes. H(2)O(2) stimulated the formation of phosphatidic acid and the accumulation of phosphatidylbutanol, a product of the phospholipase D (PLD)-catalyzed transphosphatidylation reaction. The effect of exogenous H(2)O(2) on the PLD response was mimicked by menadione-induced production of endogenous H(2)O(2). Oxidative stress also elicited inositol phosphate accumulation resulting from phosphoinositide phospholipase C (PLC) activation. The PLD response to H(2)O(2) was totally suppressed by chelation of both extracellular and cytosolic Ca(2+) with EGTA and BAPTA/AM, respectively. Furthermore, H(2)O(2)-induced PLD stimulation was completely abolished by the protein kinase C (PKC) inhibitors bisindolylmaleimide and chelerythrine and by PKC down-regulation. Activation of PLD by H(2)O(2) was also inhibited by the protein-tyrosine kinase inhibitor genistein. Finally, H(2)O(2) also stimulated both PLC and PLD in rat brain cortical slices. These results show for the first time that oxidative stress elicits phospholipid breakdown by both PLC and PLD in rat cultured astrocytes and brain slices.


Titanium dioxide nanowire sensor array integration on CMOS platform using deterministic assembly.
Nanosensor arrays have recently received significant attention due to their utility in a wide range of applications, including gas sensing, fuel cells, internet of things, and portable health monitoring systems. Less attention has been given to the production of sensor platforms in the μW range for ultra-low power applications. Here, we discuss how to scale the nanosensor energy demand by developing a process for integration of nanowire sensing arrays on a monolithic CMOS chip. This work demonstrates an off-chip nanowire fabrication method; subsequently nanowires link to a fused SiO2 substrate using electric-field assisted directed assembly. The nanowire resistances shown in this work have the highest resistance uniformity reported to date of 18%, which enables a practical roadmap towards the coupling of nanosensors to CMOS circuits and signal processing systems. The article also presents the utility of optimizing annealing conditions of the off-chip metal-oxides prior to CMOS integration to avoid limitations of thermal budget and process incompatibility. In the context of the platform demonstrated here, directed assembly is a powerful tool that can realize highly uniform, cross-reactive arrays of different types of metal-oxide nanosensors suited for gas discrimination and signal processing systems.


Functional lung avoidance and response-adaptive escalation (FLARE) RT: Multimodality plan dosimetry of a precision radiation oncology strategy.
Nonsmall cell lung cancer (NSCLC) patient radiation therapy (RT) is planned without consideration of spatial heterogeneity in lung function or tumor response. We assessed the dosimetric and clinical feasibility of functional lung avoidance and response-adaptive escalation (FLARE) RT to reduce dose to [99m Tc]MAA-SPECT/CT perfused lung while redistributing an escalated boost dose within [18 F]FDG-PET/CT-defined biological target volumes (BTV). Eight stage IIB-IIIB NSCLC patients underwent FDG-PET/CT and MAA-SPECT/CT treatment planning scans. Perfused lung objectives were derived from scatter/collimator/attenuation-corrected MAA-SPECT uptake relative to ITV-subtracted lung to maintain < 20 Gy mean lung dose (MLD). Prescriptions included 60 Gy to the planning target volume (PTV) and concomitant boost of 74 Gy mean to biological target volumes (BTV = GTV + PET gradient segmentation) scaled to each BTV voxel by relative FDG-PET SUV. Dose-painting-by-numbers prescriptions were integrated into commercial treatment planning systems via uptake threshold discretization. Dose constraints for lung, heart, cord, and esophagus were defined. FLARE RT plans were optimized with volumetric modulated arc therapy (VMAT), proton pencil beam scanning (PBS) with 3%-3 mm robust optimization, and combination of PBS (avoidance) plus VMAT (escalation). The high boost dose region was evaluated within a standardized SUVpeak structure. FLARE RT plans were compared to reference VMAT plans. Linear regression between radiation dose to BTV and normalized FDG PET SUV at every voxel was conducted, from which Pearson linear correlation coefficients and regression slopes were extracted. Spearman rank correlation coefficients were estimated between radiation dose to lung and normalized SPECT uptake. Dosimetric differences between treatment modalities were evaluated by Friedman nonparametric paired test with multiple sampling correction. No unacceptable violations of PTV and normal tissue objectives were observed in 24 FLARE RT plans. Compared to reference VMAT plans, FLARE VMAT plans achieved a higher mean dose to BTV (73.7 Gy 98195. 61.3 Gy), higher mean dose to SUVpeak (89.7 Gy vs. 60.8 Gy), and lower mean dose to highly perfused lung (7.3 Gy vs. 14.9 Gy). These dosimetric gains came at the expense of higher mean heart dose (9.4 Gy vs. 5.8 Gy) and higher maximum cord dose (50.1 Gy vs. 44.6 Gy) relative to the reference VMAT plans. Between FLARE plans, FLARE VMAT achieved higher dose to the SUVpeak ROI than FLARE PBS (89.7 Gy vs. 79.2 Gy, P = 0.01), while FLARE PBS delivered lower dose to lung than FLARE VMAT (11.9 Gy vs. 15.6 Gy, P < 0.001). Voxelwise linear dose redistribution slope between BTV dose and FDG PET uptake was higher in magnitude for FLARE PBS + VMAT (0.36 Gy per %SUVmax ) compared to FLARE VMAT (0.27 Gy per %SUVmax ) or FLARE PBS alone (0.17 Gy per %SUVmax ). FLARE RT is clinically feasible with VMAT and PBS. A combination of PBS for functional lung avoidance and VMAT for FDG PET dose escalation balanced target and normal tissue objective tradeoffs. These results provide a technical platform for testing of FLARE RT safety and efficacy within a precision radiation oncology trial.


Workplace Violence in Asian Emergency Medical Services: A Pilot Study.
Workplace violence among Asian emergency medical services (EMS) has rarely been examined. A cross-sectional, mainly descriptive study using a standardized, paper-based, self-reported questionnaire survey was conducted between August and October 2018 among emergency medical technicians (EMTs) in the Tainan City Fire Bureau, Taiwan. A total of 152 EMT-paramedics responded to the questionnaire survey, constituting an overall response rate of 96.2%. The participants were predominantly male (96.1%), college-educated (4-year bachelor's degree) (49.3%), and middle-aged (35-44 years old) (63.8%). Among them, 113 (74.3%) and 75 (49.3%) participants had experienced verbal and physical assaults at work, respectively. Only 12 (7.9%) participants were familiar with relevant regulations or codes. The assaults predominantly occurred during evening shifts (16:00-24:00) and at the scene of the emergency. The most predominant violence perpetrators included patients, patients' families, or patients' friends. Nearly 10% of participants had experienced verbal assaults from hospital personnel. EMTs who encountered workplace violence rarely completed a paper report, filed for a lawsuit, or sought a psychiatric consultation. Fifty-eight (38.2%) and 16 (10.5%) participants were victims of frequent (at least once every 3 months) verbal and physical forms of violence, respectively; however, no statistically significant association was observed in terms of EMT gender, age, working years, education level, or the number of EMS deployments per month. The prevalence of workplace violence among Asian EMS is considerable and is comparable to that in Western countries. Strategies to prevent workplace violence should be tailored to local practice and effectively implemented.


Body perception: do parents, their children, and their children's physicians perceive body image differently?
To compare children's, parents' and physicians' perceptions of children's body size. We administered a structured questionnaire of body size perception using a descriptive Likert scale keyed to body image figures to children ages 12 to 18 years. The same scale was given to parents of children ages 5 to 18 years. The sample consisted of 91 children and their parents being seen in the Pediatric Gastroenterology Clinic for concerns unrelated to overweight. Weight and height of the children were measured, and body mass index (BMI) was calculated. The children's BMI percentiles were categorized as underweight (<15th), normal (15th-85th), overweight (85th-95th), and obese (95th and above). The attending physician independently completed the body image and description scale and indicated the figure that most accurately represented the patient without reference to BMI standards. Accuracy of the patients', parents', and doctors' estimates were statistically compared. The sample population consisted of 6.4% underweight, 70.5% normal weight, 7.7% overweight, and 15.4% obese. Forty-four percent of parents underestimated children's body size using word descriptions and 47% underestimated using figures. Forty percent of the children underestimated their own body size using descriptions and 43% underestimated using figures. The physicians in this study had a higher percentage of correct estimates; however, they underestimated 33% of the patients using both word descriptions and figures. Some obese children were not recognized, and several average children were perceived as underweight. Many children underestimated their degree of overweight. Their parents and even their attending physicians shared this misperception. This study demonstrates the need to further educate physicians to recognize obesity and overweight so that they can counsel children and their families.


Establishing an integrated, four-dimensional quality assessment system for traditional Chinese medicine: A case study of Shuanghuanglian oral liquid.
The quality of traditional Chinese medicine (TCM) is the premise to ensure its safety and effectiveness in clinical application. In this study, a complete quality control system for four-dimensional fingerprinting of TCM was innovatively constructed based on multiple detection techniques, and the quality of Shuanghuanglian oral liquid (SHL) was evaluated. Electrochemical fingerprinting (ECFP) as an emerging method without pretreatment provides rich and quantifiable information for SHL samples. The first quantitative ECFP of SHL was developed by the B-Z oscillation system. Eight characteristic parameters were analyzed and a good linear relationship was found between the oscillation lifetime and sample volume, by which the calculated values of the added sample volume (VL) showed different fluctuations between samples. What is more, high-performance liquid chromatography five-wavelength fusion fingerprint (HPLC-FWFP), GC fingerprint (GC-FP), and UV quantum fingerprint (UV-QFP) was established. Meanwhile, the purity of the peaks of the HPLC-FWFP was verified by the dual-wavelength absorption coefficient ratio spectrum (DWAR). Equal weighted ratio quantitative fingerprinting method (EWRQFM) was successfully proposed to extract all potential features for the overall quality assessment of the samples. Finally, a comprehensive evaluation strategy was proposed, namely the variation coefficient weighting algorithm (VCWA). The results of qualitative and quantitative evaluation of HPLC-FWFP, GC-FP, electrochemical quantum fingerprints (EC-QFP), and UV-QFP were integrated by this method. The established evaluation system is also a suitable strategy to control the quality of other TCM preparations.


Protein binding of mercury in milk and plasma from mice and man--a comparison between methylmercury and inorganic mercury.
Inorganic mercury has previously been shown to be excreted to milk from plasma to a higher extent than methylmercury. Protein binding of mercury as methylmercury and inorganic mercury in whey and plasma from mouse and man was studied in order to get a better understanding of the transport of mercury into milk. Mice were administered a single i.v. dose of 0.25 mg Hg/kg body weight labelled with (CH3)203HgCl or 203HgCl2, resulting in 11 ng Hg/g milk and 38 ng Hg/g milk after 1 h, respectively. Milk and plasma from mice and man were also incubated with the respective radiolabelled compound (150 ng Hg/g milk or plasma). Casein, fat and whey fractions in milk from methylmercury treated mice were found to contain 11, 39 and 34%, respectively, and from inorganic mercury treated mice 31, 15 and 41%, respectively, of the total amount of mercury in milk. Serum albumin was a major mercury binding protein in whey and plasma from mice for both methylmercury and inorganic mercury, as demonstrated by FPLC gel filtration and anion-exchange chromatography and further characterised by SDS-PAGE for whey. In addition, anion-exchange chromatography indicated that inorganic mercury, but not methylmercury, in whey from mouse milk formed a dimer of serum albumin. The unbound fraction of mercury in whey and plasma from mice was very small (<0.7%), and somewhat higher in plasma and whey from man. It is concluded, that the unbound fraction in plasma cannot be a determining factor for the observed differences in milk excretion between the two mercury compounds. Instead, it is suggested that methylmercury and to some extent inorganic mercury are transferred from plasma into milk using albumin as a passive carrier.


[Toxic liver disease due to drugs, herbs and dietary supplements: diagnostic approaches].
Toxic liver diseases caused by drugs, herbs and dietary supplements are often recognized late because their hepatotoxic potency is considered to be minimal or non-existent and specific laboratory parameters to definitively establish the diagnosis are lacking. As gold standard for the diagnosis, a positive (unintentional) re-exposure test is considered which is seldom available. A system for evaluation is therefore necessary which takes into account various parameters and defines the grades of causality. By means of a qualitative pre-test with a few questions a screening may be possible as to whether the causality is not probable or not evaluable. Subsequently, a quantitative assessment of the degree of the causality with a main test should be done; this corresponds to the slightly modified and well validated score of the CIOMS (Council for International Organizations of Medical Sciences). The evaluation is achieved using various criteria such as latency period, time between the end of the therapy and begin of the reaction, course of values for the enzyme activities of the liver after cessation of the therapy, risk factors such as age, alcohol consumption and comedication, exclusion of diseases of other organs including chronic liver disease, previous information about hepatotoxicity of the alleged substance and possible results of an unwanted re-exposure. The various answers to these questions are quantitatively assessed, the resulting scores added, and finally an assignment to one of the grades of causality is made. If, on the basis of the main test, there are still doubts about the correct diagnosis, a further test is required to consider the differential diagnosis of additional diseases and chronic liver diseases of other causes. This stepwise approach is essential since ad-hoc decisions regarding causality are not without problems, and other diseases as causes for increased liver values are easily overlooked and not treated adequately in time. By means of this procedure an improvement in the drug safety can be expected, which is fruitful for the patient and helpful to the physician in charge, the health institutions and the drug companies.


Attainment and maintenance of pubertal cyclicity may predict reproductive longevity in beef heifers†.
We hypothesized the manner that heifers achieve puberty may indicate their future reproductive longevity. Heifers with discontinued or delayed cyclicity during puberty attainment may have irregular reproductive cycles, anovulation, and infertility in their first breeding season contributing to a shorter reproductive lifespan. Therefore, plasma progesterone (P4) was measured from weaning to breeding on 611 heifers born 2012-2017 and four pubertal classifications were identified: (1) Early; P4 ≥ 1 ng/ml < March 12 with continued cyclicity, (2) Typical; P4 ≥ 1 ng/ml ≥ March 12 with continued cyclicity, (3) Start-Stop; P4 ≥ 1 ng/ml but discontinued cyclicity, and (4) Non-Cycling; no P4 ≥ 1 ng/ml. Historical herd records indicated that 25% of heifers achieved puberty prior to March 12th in the 10 years prior to the study. Start-Stop and Non-Cycling yearling heifers were lighter indicating reduced growth and reproductive maturity traits compared with Early/Typical heifers. In addition, Non-Cycling/Start-Stop heifers were less responsive to prostaglandin F2 alpha (PGF2α) to initiate estrous behavior and ovulation to be artificially inseminated. Non-Cycling heifers had fewer reproductive tract score-5 and reduced numbers of calves born in the first 21-days-of-calving during their first breeding season. Within the Start-Stop classification, 50% of heifers reinitiated cyclicity with growth traits and reproductive parameters that were similar to heifers in the Early/Typical classification while those that remained non-cyclic were more similar to heifers in the Non-Cycling group. Thus, heifers with discontinued cyclicity or no cyclicity during puberty attainment had delayed reproductive maturity resulting in subfertility and potentially a shorter reproductive lifespan.


Deficiency of huntingtin has pleiotropic effects in the social amoeba Dictyostelium discoideum.
Huntingtin is a large HEAT repeat protein first identified in humans, where a polyglutamine tract expansion near the amino terminus causes a gain-of-function mechanism that leads to selective neuronal loss in Huntington's disease (HD). Genetic evidence in humans and knock-in mouse models suggests that this gain-of-function involves an increase or deregulation of some aspect of huntingtin's normal function(s), which remains poorly understood. As huntingtin shows evolutionary conservation, a powerful approach to discovering its normal biochemical role(s) is to study the effects caused by its deficiency in a model organism with a short life-cycle that comprises both cellular and multicellular developmental stages. To facilitate studies aimed at detailed knowledge of huntingtin's normal function(s), we generated a null mutant of hd, the HD ortholog in Dictyostelium discoideum. Dictyostelium cells lacking endogenous huntingtin were viable but during development did not exhibit the typical polarized morphology of Dictyostelium cells, streamed poorly to form aggregates by accretion rather than chemotaxis, showed disorganized F-actin staining, exhibited extreme sensitivity to hypoosmotic stress, and failed to form EDTA-resistant cell-cell contacts. Surprisingly, chemotactic streaming could be rescued in the presence of the bivalent cations Ca(2+) or Mg(2+) but not pulses of cAMP. Although hd(-) cells completed development, it was delayed and proceeded asynchronously, producing small fruiting bodies with round, defective spores that germinated spontaneously within a glassy sorus. When developed as chimeras with wild-type cells, hd(-) cells failed to populate the pre-spore region of the slug. In Dictyostelium, huntingtin deficiency is compatible with survival of the organism but renders cells sensitive to low osmolarity, which produces pleiotropic cell autonomous defects that affect cAMP signaling and as a consequence development. Thus, Dictyostelium provides a novel haploid organism model for genetic, cell biological, and biochemical studies to delineate the functions of the HD protein.


Vanadium--an element of atypical biological significance.
The biological image of the transition element vanadium ferments a great deal of contradiction-from toxicity to essentiality. Importance of this element as micro-nutrient is yet to be unequivocally accepted by biologists and biomedical scientists. In spite of toxicity, it seems interesting to analyze the different biological roles of the element. Vanadium compounds have been proven to be associated with various implications in the pathogenesis of some human diseases and also in maintaining normal body functions. Salts of vanadium interfere with an essential array of enzymatic systems such as different ATPases, protein kinases, ribonucleases and phosphatases. While vanadium deficiency accounts for several physiological malfunctionings including thyroid, glucose and lipid metabolism, etc., several genes are regulated by this element or by its compounds, which include genes for tumor necrosis factor-alpha (TNF-alpha), Interleukin-8 (IL-8), activator protein-1 (AP-1), ras, c-raf-1, mitogen activated protein kinase (MAPK), p53, nuclear factors-kappaB, etc. All these seem to be not far from its recognition as an element of pharmacological and nutritional significance, which is revealed through its increasing therapeutic uses in diabetes. Vanadium is also emerging as a potent anti-carcinogenic agent. This review summarizes the developments related to vanadium biology as a whole by analyzing the general biochemical functions of vanadium.


Bidirectional Cross-Talk between Biliary Epithelium and Th17 Cells Promotes Local Th17 Expansion and Bile Duct Proliferation in Biliary Liver Diseases.
There is no effective treatment for autoimmune biliary diseases. Therefore, understanding their immunopathology is crucial. The biliary epithelial cells (BEC), expressing TLR-4, are constantly exposed to gut microbes and bacterial wall LPS, and in settings of inflammation, the immune infiltrate is dense within the peribiliary region of human liver. By dual immunohistochemistry, we affirm human intrahepatic T cell infiltrate includes CCR6+CD4+ and AhR+CD4+ T cells with potential for plasticity to Th17 phenotype. Mechanistically, we demonstrate that Th1 and Th17 inflammatory cytokines and LPS enhance human primary BEC release of the CCR6 ligand CCL20 and BEC secretion of Th17-polarizing cytokines IL-6 and IL-1β. Cell culture assays with human BEC secretome showed that secretome polarizes CD4 T cells toward a Th17 phenotype and supports the survival of Th17 cells. BEC secretome did not promote Th1 cell generation. Additionally, we give evidence for a mutually beneficial feedback of the type 17 cell infiltrate on BEC, showing that treatment with type 17 cytokines increases BEC proliferation, as monitored by Ki67 and activation of JAK2-STAT3 signaling. This study identifies human BEC as active players in determining the nature of the intrahepatic immune microenvironment. In settings of inflammation and/or infection, biliary epithelium establishes a prominent peribiliary type 17 infiltrate via recruitment and retention and enhances polarization of intrahepatic CD4 cells toward Th17 cells via type 17 cytokines, and, reciprocally, Th17 cells promote BEC proliferation for biliary regeneration. Altogether, we provide new insight into cross-talk between Th17 lymphocytes and human primary biliary epithelium in biliary regenerative pathologies.


Pathogenesis and natural history of HIV infection.
Acquired immune deficiency syndrome (AIDS) is caused by infection with the human immunodeficiency virus (HIV), a human retrovirus. The virus infects cells of the immune system by attachment of a glycoprotein viral envelope (gp 120) to a molecule expressed on human helper T cells called CD4. The fusion of the virus envelope protein to its specific receptor allows HIV to penetrate the T cell. Once inside the cell viral RNA is transcribed into double-stranded DNA by an enzyme unique to retroviruses, reverse transcriptase. The double-stranded, proviral DNA travels to the nucleus of the cell and is integrated into the infected cell's chromosomal DNA where it may remain latent for years. As a result of triggers that are poorly understood, viral replication becomes activated and proviral DNA is transcribed back into genomic RNA and RNA that is translated into viral proteins, both of which are packaged and bud from the infected T cell as infectious virus. The viral life cycle orchestrates the natural history of clinical HIV infection. Three to four weeks following exposure to HIV there is a phase of rapid viral replication, high levels of plasma viremia, and development of a "flue like" illness. Four to six weeks after exposure, during this stage of acute infection, antibodies to HIV core (p24) and envelope (gp 160, gp 120, gp41) proteins appear. Six to eight weeks after exposure symptoms disappear and plasma viremia subsides, presumably due to clearance by the immune system.(ABSTRACT TRUNCATED AT 250 WORDS)


Serotonergic Modulation of Nociceptive Circuits in Spinal Cord Dorsal Horn.
Despite the extensive number of studies performed in the last 50 years, aimed at describing the role of serotonin and its receptors in pain modulation at the spinal cord level, several aspects are still not entirely understood. The interpretation of these results is often complicated by the use of different pain models and animal species, together with the lack of highly selective agonists and antagonists binding to serotonin receptors. In this review, a search has been conducted on studies investigating the modulatory action exerted by serotonin on specific neurons and circuits in the spinal cord dorsal horn. Particular attention has been paid to studies employing electrophysiological techniques, both in vivo and in vitro. The effects of serotonin on pain transmission in dorsal horn depend on several factors, including the type of receptors activated and the populations of neurons involved. Recently, studies performed by activating and/or recording from identified neurons have importantly contributed to the understanding of serotonergic modulation on dorsal horn circuits.


Quantitizing findings from qualitative studies for integration in mixed methods reviewing.
In mixed methods reviewing, data from quantitative and qualitative studies are combined at the review level. One possible way to combine findings of quantitative and qualitative studies is to quantitize qualitative findings prior to their incorporation in a quantitative review. There are only a few examples of the quantification of qualitative findings within this context. This study adds to current research on mixed methods review methodology by reporting the pilot implementation of a new four-step quantitizing approach. We report how we extract and quantitize the strength of relationships found in qualitative studies by assigning correlations to vague quantifiers in text fragments. This article describes (a) how the analysis is prepared; (b) how vague quantifiers in text fragments are organized and transformed to numerical values; (c) how qualitative studies as a whole are assigned effect sizes; and (d) how the overall mean effects size and variance can be calculated. The pilot implementation shows how findings from 26 primary qualitative studies are transformed into mean effect sizes and corresponding variances.


Coxsackievirus B3 infection induces cyr61 activation via JNK to mediate cell death.
Coxsackievirus B3 (CVB3), an enterovirus in the Picornavirus family, is the most common human pathogen associated with myocarditis and idiopathic dilated cardiomyopathy. We found upregulation of the cysteine-rich protein gene (cyr61) after CVB3 infection in HeLa cells with a cDNA microarray approach, which is confirmed by Northern blot analysis. It is also revealed that the extracellular amount of Cyr61 protein was increased after CVB3 infection in HeLa cells. cyr61 is an early-transcribed gene, and the Cyr61 protein is secreted into the extracellular matrix. Its function is related to cell adhesion, migration, and neuronal cell death. Here, we show that activation of the cyr61 promoter by CVB3 infection is dependent on JNK activation induced by CVB3 replication and viral protein expression in infected cells. To explore the role of Cyr61 protein in infected HeLa cells, we transiently overexpressed cyr61 and infected HeLa cells with CVB3. This increased CVB3 growth in the cells and promoted host cell death by viral infection, whereas down-expression of cyr61 with short interfering RNA reduced CVB3 growth and showed resistance to cell death by CVB3 infection. In conclusion, we have demonstrated a new role for cyr61 in HeLa cells infected with CVB3, which is associated with the cell death induced by virus infection. These data thus expand our understanding of the physiological functions of cyr61 in virus-induced cell death and provide new insights into the cellular factors involved.


[Helicobacter pylori, 13 years after the original publication].
Helicobacter pylori a gram negative bacilli is related with development of gastroduodenal disease as chronic active gastritis, peptic ulcer disease MALT type lymphomas and gastric cancer. The WHO defined H. pylori as a human carcinogen agent. Helicobacter colonizes the gastric epithelium and promotes inflammation and mucosal damage. Third part of the world's population is infected by the bacteria and many researchers consider that the mode of transmission between human being is via the fecal-oral and/or oral-oral manner. H. pylori may be identified in saliva, gastric juice, gastric biopsies and feces by different methods. The eradication of this microorganism disminished the gastrointestinal tract disease.


Species dependence of the major late promoter in adenovirus type 12 DNA.
In hamster cells human adenovirus type 12 (Ad12) is deficient in DNA replication and late gene expression whereas adenovirus type 2 (Ad2) can replicate. Functions located in the E1 region of the Ad2 or adenovirus type 5 (Ad5) genome can complement the deficiencies of the Ad12 genome in hamster cells, but, infectious viral particles are not produced. We have now investigated the activity of the major late promoter of Ad2 and of Ad12 DNA in human and hamster cells. This promoter governs the expression of most of the late viral functions. We have inserted the major late promoter (MLP) of Ad2 or of Ad12 DNA in front of the chloramphenicol acetyl transferase gene in the pSVO-CAT construct. Upon transfection into uninfected human and hamster cells, the pAd12MLP-CAT construct shows no significant activity; the pAd2MLP-CAT construct exhibits low activity. In Ad12-infected human cells, both constructs are active. These findings support the notion that other viral factors are required for MLP activity of Ad2 or Ad12 DNA in permissive human cells. In Ad2-infected hamster cells, both the pAd2MLP-CAT and the pAd12MLP-CAT constructs are active. Apparently, the Ad12 MLP can be activated by Ad2 functions, as already demonstrated for the entire Ad12 genome in double-infected cells or in Ad2- or Ad5-transformed cells superinfected with Ad12. In Ad12-infected hamster cells, however, the MLP of Ad12 DNA is inactive but that of Ad2 DNA shows activity. Thus the MLP of Ad12 DNA somehow differentiates between cellular auxiliary functions of different species.(ABSTRACT TRUNCATED AT 250 WORDS)


Overall and cause-specific mortality in transplant recipients with a pretransplantation cancer history.
It is unclear to what extent cancer history affects posttransplantation mortality in solid organ transplant recipients. We identified a Swedish population-based cohort of solid organ transplant recipients in the National Patient Register 1970 to 2008 and linked it to the Cancer and Cause-of-Death Register. Overall and cause-specific mortality was estimated using Cox regression. Of 10,448 eligible recipients, 416 (4%) had a prior malignancy unrelated to the indication for transplantation diagnosed 2 months or more before surgery (median, 5.7 years). Mortality among cancer history recipients was 30% increased after transplantation, compared with other recipients (adjusted hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.1-1.5; P<0.001), driven by cancer-specific death with no increase in cardiovascular, infectious, or other noncancer mortality. An increased rate of death due to cancer history was primarily observed among nonkidney recipients (adjusted HR(nonkidney), 1.8; 95% CI, 1.3-2.5; HR(kidney), 1.2; 95% CI, 1.0-1.4). Rates were greatest for patients with waiting times of 5 years or less but persisted with waiting times more than 10 years among kidney and nonkidney recipients with prior aggressive cancer types (gastrointestinal, breast, kidney/urothelial, and hematologic malignancies). We conclude that organ transplant recipients with cancer history are at a moderately increased rate of death after transplantation, driven primarily by death due to cancer recurrence.


Automated Creation of Expert Systems with the InteKRator Toolbox.
Expert systems have a long tradition in both medical informatics and artificial intelligence research. Traditionally, such systems are created by implementing knowledge provided by experts in a system that can be queried for answers. To automatically generate such knowledge directly from data, the lightweight InteKRator toolbox will be introduced here, which combines knowledge representation and machine learning approaches. The learned knowledge is represented in the form of rules with exceptions that can be inspected and that are easily comprehensible. An inference module allows for the efficient answering of queries, while at the same time offering the possibility of providing explanations for the inference results. The learned knowledge can be revised manually or automatically with new evidence after learning.


Soy protein isolate reduces hepatosteatosis in yellow Avy/a mice without altering coat color phenotype.
Agouti (A(vy)/a) mice fed an AIN-93G diet containing the soy isoflavone genistein (GEN) prior to and during pregnancy were reported to shift coat color and body composition phenotypes from obese-yellow towards lean pseudoagouti, suggesting epigenetic programming. Human consumption of purified GEN is rare and soy protein is the primary source of GEN. Virgin a/a female and A(vy)/a male mice were fed AIN-93G diets made with casein (CAS) or soy protein isolate (SPI) (the same approximate GEN levels as in the above mentioned study) for 2 wks prior to mating. A(vy)/a offspring were weaned to the same diets and studied at age 75 d. Coat color distribution did not differ among diets, but SPI-fed, obese A(vy)/a offspring had lower hepatosteatosis (P < 0.05) and increased (P < 0.05) expression of CYP4a 14, a PPARalpha-regulated gene compared to CAS controls. Similarly, weanling male Sprague-Dawley (SD) rats fed SPI had elevated hepatic Acyl Co-A Oxidase (ACO) mRNA levels and increased in vitro binding of PPARalpha to the PPRE promoter response element. In another hepatosteatosis model, adult SD rats fed a high fat/cholesterol diet, SPI reduced (P < 0.05) steatosis. Thus, 1) consumption of diets made with SPI partially protected against hepatosteatosis in yellow mice and in SD rats, and this may involve induction of PPARalpha-regulated genes; and 2) the lifetime (in utero, neonatal and adult) exposure to dietary soy protein did not result in a shift in coat color phenotype of A(vy)/a mice. These findings, when compared with those of previously published studies of A(vy)/a mice, lead us to conclude that: 1) the effects of purified GEN differ from those of SPI when GEN equivalents are closely matched; 2) SPI does not epigenetically regulate the agouti locus to shift the coat color phenotype in the same fashion as GEN alone; and 3) SPI may be beneficial in management of non-alcoholic fatty liver disease.


A Core Structural Protein That Builds the Locust Mandible with a Mechanical Gradient.
Natural materials, such as locust mandibles and squid beaks, define significant mechanical gradients that have been attributed to the chemical gradients of their specialized structural proteins (SPs). However, the mechanism by which SPs form chemical gradients in these materials remains unknown. In this study, a highly abundant histidine-rich structural protein (LmMHSP) was identified in the mandible of a migratory locust (Locusta migratoria). LmMHSP was proven by both in vivo and in vitro evidence to act as a core building block of the mandible with a variety of synergistic functions including chitin binding, matrix formation via liquid-liquid phase separation, chemical cross-linking, and metal coordination. Furthermore, we found that the SP gradient in the locust mandible stems from the chitin-binding activity of LmMHSP and different microstructures of chitin scaffolds in different regions. These findings advance our understanding of the formation mechanisms of natural biomaterials and have implications for the fabrication of biomimetic materials.


Global overview of injecting drug use and HIV infection among injecting drug users.
To provide global estimates of the prevalence of injecting drug use (IDU) and HIV prevalence among IDU, in particular to provide estimates for developing and transitional countries. Collation and review of existing estimates of IDU prevalence and HIV prevalence from published and unpublished documents for the period 1998-2003. The strength of evidence for the information was assessed based on the source and type of study. Estimates of IDU prevalence were available for 130 countries. The number of IDU worldwide was estimated as approximately 13.2 million. Over ten million (78%) live in developing and transitional countries (Eastern Europe and Central Asia, 3.1 million; South and South-east Asia, 3.3 million; East-Asia and Pacific, 2.3 million). Estimates of HIV prevalence were available for 78 countries. HIV prevalence among IDU of over 20% was reported for at least one site in 25 countries and territories: Belarus, Estonia, Kazakhstan, Russia, Ukraine, Italy, Netherlands, Portugal, Serbia and Montenegro, Spain, Libya, India, Indonesia, Malaysia, Myanmar, Nepal, Thailand, Viet Nam, China, Argentina, Brazil, Uruguay, Puerto Rico, USA and Canada. These findings update previous assessments of the number of countries with IDU and HIV-infected IDU, and the previous quantitative global estimates of the prevalence of IDU. However, gaps remain in the information and the strength of the evidence often was weak.


Pesticide application practices, pest knowledge, and cost-benefits of plantain production in the Bribri-Cabécar Indigenous Territories, Costa Rica.
The use of pesticides in the cultivation of cash crops such as banana and plantain is increasing, in Costa Rica and worldwide. Agrochemical use and occupational and environmental exposures in export banana production have been documented in some parts of Central America. However, the extent of agrochemical use, agricultural pest knowledge, and economic components in plantain production are largely unknown in Costa Rica, especially in remote, high-poverty areas such as the Bribri-Cabécar Indigenous Territories. Our objective was to integrate a rapid rural appraisal of indigenous farmer pesticide application practices and pest knowledge with a cost-benefit analysis of plantain production in the Bribri-Cabécar Indigenous Territories, for the development of better agricultural management practices and improved regulatory infrastructure. Interviews conducted with 75 households in 5 indigenous communities showed that over 60% of participants grew plantain with agrochemicals. Of these plantain farmers, over 97% used the insecticide chlorpyrifos, and 84% applied nematicides, 64% herbicides, and 22% fungicides, with only 31% of participants reporting the use of some type of protective clothing during application. The banana weevil (Cosmopolites sordidus Germar) was ranked as the most important agricultural pest by 85% of participants, yet only 28% could associate the adult and larval form. A cost-benefit analysis conducted with a separate group of 26 plantain farmers identified several national markets and one export market for plantain production in the Indigenous Territories. Yearly income averaged US$6200/ha and yearly expenses averaged US$1872/ha, with an average cost-benefit ratio of 3.67 for plantain farmers. Farmers applied an average of 9.7 kg a.i./ha/yr of pesticide products and 375 kg/ha/yr of fertilizer, but those who sold their fruit to the national markets applied more nematicides, herbicides, and fertilizers than those who sold primarily to export markets, suggesting a lack of appropriate application knowledge. Results indicate that the quantity of agrochemicals applied in plantain cultivation is less than that applied in export banana, but the absence of appropriate agrochemical application practices in plantain cultivation may pose serious risks to human and environmental health. Culturally appropriate farmer education and certification programs are needed as well as the development of safe-handling practices, regulatory infrastructure, and adequate agrochemical storage, transport, and waste disposal facilities. Long-term solutions however, are dependent on the development of policies and infrastructure that support non-chemical pest management, alternatives to pesticides, and the identification of organic plantain markets.


A preliminary study on the evaluation of photodynamic diagnosis for acne inflammatory skin lesions.
This study aimed to observe the fluorescence characteristics of acne inflammatory skin lesions in 5-aminolevulinic acid-based photodynamic diagnosis (ALA-PDD), and discuss the viability of using ALA-PDD to evaluate acne inflammatory skin lesions and explore the advantages of predicting subclinical skin lesions. The OBSERV facial skin detector collected photographs of 20 patients before and after optical intra-tissue fiber irradiation photodynamic therapy (OFI-ALA-PDT) in both ALA-PDD and white light patterns. The patients were treated once a week for four consecutive weeks in order to analyze the correlation between the two patterns in recognizing inflammatory skin lesions. Before and after treatment, there was no significant difference between the two patterns for recognizing acne inflammatory skin lesions (p > 0.05). Both patterns demonstrated a strong correlation (r > 0.90) for the recognition of various types of inflammatory skin lesions at different treatment stages. ALA-PDD is a feasible method for evaluating acne inflammatory lesions, guiding treatment and judging efficacy. It has advantages in predicting subclinical skin lesions and deserves further study.


[The frame of non-canonical theory of heredity: from genes to epigenes].
Particular theory of heredity that exceeds the limits of mendelian genetics is suggested. The model based on five sufficiently obvious assumptions (accepted as axioms) As consequence of these axioms the strict statements concerningfunctional heredity memory were formulated in mathematical terms. Molecular-genetic realization of the memory cells appears as new class of heredity units--epigenes. In the epigenes part f hereditary information is contained, encoded and transmitted beyond the primary structure of DNA molecules of genome. Epigenes capable to conserve sequences of genes functional states in the course of ontogenesis and provide transmission of information contained in this states throw consequent generations. It was shown that epigenes differ from genes at least by encoding method of heredity information. There are three functional-equivalent classes of really existing epigenes mechanisms: dynamic, modificational and transpositional; and there is one hypothetical class--invertional. It was shown that a lot of experimental data concerning epigenetic mechanism of heredity is in accord with theoretical conclusions concerning epigenes existence. Moreover, we constructed an artificial epigenes by genetic engineering methods. The existence of epigenes means that obtaining complete genome sequence, its physical and genetic maps, as well as distinguishing the rules of genes function encoding by its primary structure do not provide complete decoding of hereditary information. The role of epigenes in ontogenesis and phylogenesis was examined. It was shown that even elementary epigenetic systems could determine key ontogenesis events. Epigenetic system could serve as the basis of non-darwinian evolutionary strategies by means of "memorization of rather unsuccessfully steps of evolution" and conservation of alternative variants of ontogenesis. Teleonomic hypothesis on functional heredity memory was formulated. This theory provides explanation of phenomena of acquired features inheritance and molecular mechanisms of stress-induced evolution.


Construction and validation of a mitochondria-associated genes prognostic signature and immune microenvironment characteristic of sepsis.
Sepsis is a common critical condition seen in clinical settings, with mitochondrial dysfunction playing an important role in the progression of sepsis. However, a mitochondrial prognosis model related to sepsis has not been established yet, and the relationship between the sepsis immune microenvironment and mitochondria remains unclear. Sepsis prognostic mitochondria-associated genes (MiAGs) were screened by univariate Cox, multivariate Cox, and LASSO analysis from the GEO dataset. Consensus Cluster was used to analyze MiAGs-based molecular subtypes for sepsis. The ESTIMATE and ssGSEA algorithms were used to analyze the situation of sepsis immune cell infiltration and its relation to MiAGs. Further, MiAGs score was calculated to construct a sepsis prognosis risk model to predict the prognosis of sepsis patients. Clinical blood samples were used to investigate the expression level of selected MiAGs in sepsis. Single-cell sequencing analysis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and ATP detection were used to verify the influence of MiAGs on mitochondrial dysfunction in sepsis. A total of 5 MiAGs of sepsis were screened. Based on MiAGs, sepsis MiAGs subtypes were analyzed, where Cluster A had a better prognosis than Cluster B, and there were significant differences in immune infiltration between the two clusters. The sepsis mitochondrial prognosis model suggested that the high MiAG score group had a shorter survival time compared to the low MiAG score group. Significant differences were also observed in the immune microenvironment between the high and low MiAG score groups. Prognostic analysis and the Nomogram indicated that the MiAG score is an independent prognostic factor in sepsis. Single-cell sequencing analysis exhibited the possible influence of MiAGs on the mitochondrial function of monocytes. Finally, the downregulation of the COX7B could effectively improve mitochondrial function in the LPS-stimulated sepsis model. Our findings suggest that MiAGs can be used to predict the prognosis of sepsis and that regulating the mitochondrial prognostic gene COX7B can effectively improve the mitochondrial function of immune cells in sepsis.


[Dispneic patient: specific expectancies about the nursing assistance (part III)].
The author assesses the specific expectancies of the dispneic patient related to nursing assistance and nursing attendance. The coincidence of data obtained from informations given by both the patient and the nursing personnel is also studied.


Primary care physicians' attitudes regarding race-based therapies.
There is little to no information on whether race should be considered in the exam room by those who care for and treat patients. How primary care physicians understand the relationship between genes, race and drugs has the potential to influence both individual care and racial and ethnic health disparities. To describe physicians' use of race-based therapies, with specific attention to the case of BiDil (isosorbide dinitrate/hydralazine), the first drug approved by the FDA for a race-specific indication, and angiotensin-converting enzyme (ace) inhibitors in their black and white patients. Qualitative study involving 10 focus groups with 90 general internists. Black and white general internists recruited from community and academic internal medicine practices participated in the focus groups.Of the participants 64% were less than 45 years of age, and 73% were male. The focus groups were transcribed verbatim, and the data were analyzed using template analysis. There was a range of opinions relating to the practice of race-based therapies. Physicians who were supportive of race-based therapies cited several potential benefits including motivating patients to comply with medical therapy and promoting changes in health behaviors by creating the perception that the medication and therapies were tailored specifically for them. Physicians acknowledged that in clinical practice some medications vary in their effectiveness across different racial groups, with some physicians citing the example of ace inhibitors. However, physicians voiced concern that black patients who could benefit from ace inhibitors may not be receiving them. They were also wary that the category of race reflected meaningful differences on a genetic level. In the case of BiDil, physicians were vocal in their concern that commercial interests were the primary impetus behind its creation. Primary care physicians' opinions regarding race-based therapy reveal a nuanced understanding of race-based therapies and a wariness of their use by physicians.


A selective role for dopamine in stimulus-reward learning.
Individuals make choices and prioritize goals using complex processes that assign value to rewards and associated stimuli. During Pavlovian learning, previously neutral stimuli that predict rewards can acquire motivational properties, becoming attractive and desirable incentive stimuli. However, whether a cue acts solely as a predictor of reward, or also serves as an incentive stimulus, differs between individuals. Thus, individuals vary in the degree to which cues bias choice and potentially promote maladaptive behaviour. Here we use rats that differ in the incentive motivational properties they attribute to food cues to probe the role of the neurotransmitter dopamine in stimulus-reward learning. We show that intact dopamine transmission is not required for all forms of learning in which reward cues become effective predictors. Rather, dopamine acts selectively in a form of stimulus-reward learning in which incentive salience is assigned to reward cues. In individuals with a propensity for this form of learning, reward cues come to powerfully motivate and control behaviour. This work provides insight into the neurobiology of a form of stimulus-reward learning that confers increased susceptibility to disorders of impulse control.


Reduced fertility in vitro in mice lacking the cystatin CRES (cystatin-related epididymal spermatogenic): rescue by exposure of spermatozoa to dibutyryl cAMP and isobutylmethylxanthine.
The cystatin CRES (cystatin-related epididymal spermatogenic; Cst8) is the defining member of a reproductive subgroup of family 2 cystatins of cysteine protease inhibitors and is present in the epididymis and spermatozoa, suggesting roles in sperm maturation and fertilization. To elucidate the role of CRES in reproduction, mice lacking the Cst8 gene were generated and their fertility examined. Although both male and female Cst8(-/-) mice generated offspring in vivo, spermatozoa from Cst8(-/-) mice exhibited a profound fertility defect in vitro. Compared to spermatozoa from Cst8(+/+) mice, spermatozoa from Cst8(-/-) mice were unable to undergo a progesterone-stimulated acrosome reaction and had decreased levels of protein tyrosine phosphorylation, suggesting a defect in the ability of Cst8(-/-) spermatozoa to capacitate. Incubation of Cst8(-/-) spermatozoa with dibutyryl cAMP and 3-isobutyl-1-methylxanthine rescued the fertility defect, including the capacity for sperm protein tyrosine phosphorylation. Both untreated Cst8(+/+) and Cst8(-/-) spermatozoa, however, exhibited similar increased total levels of cAMP and protein kinase A (PKA) activity throughout the capacitation time course compared to spermatozoa incubated under noncapacitating conditions. Taken together, these results suggest that mice lacking CRES may have altered local levels of cAMP/PKA activity, perhaps because of improper partitioning or tethering of these signaling molecules, or that the CRES defect does not directly involve cAMP/PKA but other signaling pathways that regulate protein tyrosine phosphorylation and capacitation.


Pregnant Hispanic women's views and knowledge of prenatal genetic testing.
Pregnant Hispanic women are underserved with their needs for genetic counseling, despite birth defects remaining the leading cause of infant death in the United States. We present the qualitative findings of a study to understand knowledge and perceptions of prenatal testing in a sample of hard-to-reach underrepresented Hispanic pregnant women in South Texas. The sample for this study was 10 Hispanic pregnant women who were recruited from a high-risk prenatal clinic in South Texas in 2019. The semi-structured interview questions were created based on the researchers' clinical experiences with this population and were designed to examine knowledge and perceptions of participants toward prenatal testing. Analysis of the qualitative data yielded several themes related to prenatal testing: (a) knowledge, (b) confusion, (c) partner's and support persons' opinions, (d) information sharing from providers, (e) psychological benefits, (f) preparation for baby, (g) obstacles, (h) religious influence, and (i) educational tools to assist with understanding. Women's understanding and knowledge of prenatal testing was limited, specifically regarding its purpose, how it works, the benefits, and why it was recommended by their provider. Lack of clarity about why they should take the test and its risks for them and their babies was perceived as something that could impede their acceptance of prenatal testing. All participants agreed that healthcare providers should share more information about prenatal testing in a way that uses 'everyday language' so that they can understand it better. All respondents mentioned that prenatal testing provides information about their baby's health conditions, alleviates their stress and concerns, and psychologically prepares them and their family for what is to come. Identifying ways to increase culturally appropriate education delivered by genetic counselors such as through the adoption of telemedicine and mobile technology can help fill the gap for this underserved population.


ROS1-rearranged Non-small-cell Lung Cancer is Associated With a High Rate of Venous Thromboembolism: Analysis From a Phase II, Prospective, Multicenter, Two-arms Trial (METROS).
Patients with cancer are at increased risk for venous thromboembolism (VTE), and 8% to 15% of patients with advanced non-small-cell lung cancer (NSCLC) experience a VTE event during the course of their disease. The incidence of VTE in molecularly defined NSCLC subgroups is still unclear. In this study, we investigated the incidence and the clinical correlates of VTE in patients with ROS1-rearranged NSCLC enrolled in the METROS trial (NCT02499614). The METROS trial is a prospective phase II study designed to assess efficacy, safety, and tolerability of crizotinib in patients with pre-treated metastatic NSCLC ROS1 rearrangement (cohort A) or with MET amplification or MET exon 14 mutation (cohort B). Patients with ROS1-rearranged NSCLC enrolled within cohort A and the expansion cohort of the trial were included in the primary analysis. Among 48 patients with ROS1-rearranged NSCLC enrolled in the METROS study, 20 (41.6%) of 48 had at least 1 VTE event. Among them, 7 (35%) of 20 patients had ≥ 2 VTE events. VTE events consisted of pulmonary embolism (46.4%), deep vein thrombosis (39.2%), renal vein thrombosis (7.1%), internal jugular thrombosis (3.5%), and peripheral inserted central catheter-related thrombosis (3.5%). VTE events occurred at disease progression in 35.7% of cases, at diagnosis in 32.1% of cases, and during chemotherapy or crizotinib in 17.8% and 14.2%, respectively. The incidence of VTE is 3- to 5-fold higher in patients harboring ROS1-rearrangment than previously observed for the general population with NSCLC. Larger studies are warranted to confirm our findings and determine whether the molecular profile of NSCLC should be incorporated into a risk-stratification tool and decision-making algorithm for VTE diagnosis and prophylaxis.


Autonomic effects of selegiline: possible cardiovascular toxicity in Parkinson's disease.
The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease randomised to receive selegiline (10 mg/day) and levodopa compared with those taking levodopa alone. Unwanted effects of selegiline on cardiovascular regulation have been investigated as a potential cause for the unexpected mortality finding of the UKPDRG trial. The cardiovascular responses to a range of physiological stimuli, including standing and head up tilt, were studied in patients with Parkinson's disease receiving levodopa alone and a matched group on levodopa and selegiline. Head up tilt caused selective and often severe orthostatic hypotension in nine of 16 patients taking selegiline and levodopa, but was without effect on nine patients receiving levodopa alone. Two patients taking selegiline lost consciousness with unrecordable blood pressures and a further four had severe symptomatic hypotension. The normal protective rises in heart rate and plasma noradrenaline were impaired. The abnormal response to head up tilt was reversed by discontinuation of selegiline. Drug withdrawal caused a pronounced deterioration in motor function in 13 of the 16 patients taking selegiline. Therapy with selegiline and levodopa in combination may be associated with severe orthostatic hypotension not attributable to levodopa alone. Selegiline also has pronounced symptomatic motor effects in advanced Parkinson's disease. The possibilities that these cardiovascular and motor findings might be due either to non-selective inhibition of monoamine oxidase or to amphetamine and met-amphetamine are discussed.


Tentorial detachment technique in the combined petrosal approach for petroclival meningiomas.
The combined petrosal approach is a suitable technique for the resection of medium-to-large petroclival meningiomas (PCMs). Multiple technical modifications have been reported to increase the surgical corridor, including the method of dural and tentorial opening. The authors describe their method of dural opening and tentorial resection, and detail the microanatomy related to their technique to clarify pitfalls and effects. The relationship of temporal bridging veins and cranial nerves (CNs) around the tentorial resection area was examined during the combined petrosal approach in 20 cadaveric specimens. The authors also reviewed their 23 consecutive clinical cases treated using this technique between 2002 and 2010, focusing on the effects and risks of the procedure. In the authors' method, the tentorial resection extends from 5 to 10 mm anterior to the junction of the sigmoid sinus and the superior petrosal sinus ("sinodural point") to the trigeminal fibrous ring and the dural sleeve of CN IV. Temporal bridging veins enter the transverse sinus no more than 5 mm anterior to the sinodural point. The CN IV should be freed from its tentorial dural sleeve while avoiding disruption of the posterior cavernous sinus. The clinical data demonstrate a total resection rate of 78.3%, intraoperative estimated blood loss < 400 ml at a rate of 80.9%, and a venous congestion rate of 0%. Understanding the anatomical relationship between the tentorium and temporal bridging veins and CNs IV-VI allows neurosurgeons the ability to develop a combined petrosal approach to PCMs that will effectively supply a wide operative corridor after resecting the tentorium, while significantly devascularizing tumors.


Preparing for the unexpected: the pivotal role of social and behavioral sciences in trials of biomedical HIV prevention interventions.
A range of efficacies have been reported for biomedical HIV prevention interventions, including antiretroviral treatment, male circumcision, preexposure prophylaxis, microbicides, and preventive vaccines. This range of efficacies probably results from the influence of multiple inputs and processes during trials, including the strength and target of the intervention, host factors, target population characteristics, level of HIV exposure, and intervention dose. Expertise in social and behavioral sciences, in conjunction with basic science, clinical research, epidemiology, biostatistics, and community, is needed to understand the influence of these inputs and processes on intervention efficacy, improve trial design and implementation, and enable interpretation of trial results. In particular, social and behavioral sciences provide the means for investigating and identifying populations suitable for recruitment into and retention in trials and for developing and improving measures of HIV exposure and intervention dose, all within the larger sociocultural context. Integration of social and behavioral sciences early in idea generation and study design is imperative for the successful conduct of biomedical trials and for ensuring optimal data collection approaches necessary for the interpretation of findings, particularly in cases of unexpected results.


Space dermatology: a specialty in evolution.
The last thirty years have demonstrated the ability of humans to survive both brief and prolonged durations of microgravity in the unique environment of space. The maintenance of health and well-being during spaceflight has been the focus of physicians and health care personnel involved in space medicine. It follows that dermatology will become a defined component of space medicine, as skin-related physiology and subsequent disorders are elucidated and as health maintenance protocols are developed. This information will become part of the core of what can be called space dermatology.


Lack of Patient Compliance in Real-World Practice Negatively Affects Sustained Viral Response Rates to Direct Acting Agent Therapy for Hepatitis C.
To assess the true efficacy of direct acting antiviral (DAA) therapy in real-world clinical practice, taking into account those patients that do not complete therapy or the necessary follow-up to establish sustained viral response (SVR). Retrospective data collection of 261 genotype 1 HCV-infected patients, treatment naïve or treatment experienced, treated with ledipasvir/sofosbuvir combination therapy at an academic medical center. All patients received individualized teaching and counseling prior to starting therapy stressing importance of compliance with laboratory monitoring and treatment completion. Intention to treat SVR rates (ITT-SVR) and per-protocol SVR rates (PP-SVR) were calculated. Chi-squared test was used to compare the number of subjects lost to follow-up in the treatment-naïve vs. treatment-experienced groups. Characteristics of noncompliant patients were compared to compliant patients. ITT-SVR rates for the entire cohort were 74%, significantly lower than the 95% PP-SVR rate for the compliant patients (p < 0.001). ITT-SVR was lower in treatment-naïve patients compared to treatment-experienced patients (68% vs. 86%). Among the entire cohort, 22% of patients either discontinued therapy prematurely (7%) or did not return for SVR assessment (15%). Failure to complete therapy or return for SVR assessment was statistically more common among treatment-naïve patients compared to treatment-experienced patients (28% vs. 11%, p = 0.0016). There is a significant rate of noncompliance among patients treated with DAA in real-world clinical practice despite pre-treatment education efforts. The ITT-SVR rates observed in clinical practice were significantly lower than those reported by clinical trials, and this difference was most pronounced among treatment-naïve patients.


Study of protective effect of date and nigella sativa on aflatoxin b(1) toxicity.
Many medicinal plants and their purified constituents have been shown beneficial therapeutic potentials. Seeds of Nigella sativa, a dicotyledon of the Ranunculaceae family, have been utilized for thousands of years as a spice and food preservative. the toxic effect of aflatoxin-B(1) (AFB(1)) and the possible cytoprotective effect of Nigella sativa (NS) oil and aqueous extract of date were studied on 40 male rats. The animals were divided into 4 groups (10 rats each) and treated daily for two weeks. Group 1 received normal saline as controls. Group 2 treated via intraperitoneal (IP) route with AFB(1) (50μg/kg BW). Group 3 treated with AFB(1) and NS oil via IP. Group 4 treated with AFB(1) and received orally aqueous extract of date (15mg/15ml). The liver and kidneys of each animal were histological examined and biochemical evaluation of the liver and kidney functions was performed. Group 2 showed severe degenerative and necrotic changes in the liver and kidney. The plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine and urea in AFB(1) group were significantly higher than the control group. Livers and kidneys of rats, treated with AFB(1) and NS showed less histopathological changes in comparison with the AFB(1) treated group. Livers and kidneys of rats treated with AFB1 and date group showed only mild histopathological changes in comparison with AFB(1) treated group. These histopathological changes seen in animals treated with AFB1 and dates were associated with a significant reduction in levels of ALT, AST, creatinine and urea. Likewise, histopathological changes in the AFB1 and NS group were associated with significant reduction in the levels of beforementioned indices. Moreover, AFB1 and date group showed significant improvement in liver function comparing with AFB(1) and NS group. our study revealed that treatment with AFB(1) induced histopathological changes in the tissues of liver and kidney associated with dysfunction of these organs. Both NS and date reduce the toxic effects of AFB(1) in liver and kidney. But date treatment was more cytoprotective for liver than NS treatment against aflatoxicosis in rats.


Impaired endothelial function in arterial hypertension and hypercholesterolemia: potential mechanisms and differences.
This review focuses on the role of impaired endothelial function for the development of atherosclerosis in human arterial hypertension and hypercholesterolemia in vivo. Potential mechanisms underlying impaired endothelial function and decreased bioavailability of nitric oxide under these clinical conditions are discussed and potential differences in these mechanisms between arterial hypertension and hypercholesterolemia are outlined. It further addresses therapeutic strategies aiming to improve the bioavailability of nitric oxide in these patients. The overall conclusion is that the bioavailability of nitric oxide is probably impaired not by a single defect, but by various mechanisms affecting nitric oxide synthesis as well as nitric oxide breakdown. In both diseases, increased superoxide anion production and oxidative stress represents a major mechanism. However, potential differences in the underlying mechanisms of superoxide production or nitric oxide synthesis are evident between arterial hypertension and hypercholesterolemia. Decreased bioavailability of nitric oxide does not only impair endothelium-dependent vasodilation, but also activates other mechanisms that play an important role in the pathogenesis of atherosclerosis. Thus, therapeutic strategies should aim to restore bioavailability of nitric oxide, which has been demonstrated for lipid-lowering therapy in hypercholesterolemia. The mechanisms by which nitric oxide bioavailability can be improved by any drug therapy remain to be elucidated and may provide further insights into the mechanisms that are involved in impaired endothelial function and atherogenesis.


Towards a trial-ready mobile patient questionnaire system.
Gathering patient-reported data enables physicians to know a patient and his/her health-related needs in a more comprehensive way. One method to collect these data is to let the patient fill out electronic questionnaires on a mobile device, e.g. a tablet. Although having successfully implemented a prototype, the mobile questionnaire system at this site has been stretched to its limits within both routine care and clinical trials. By collecting user feedback and analysing the capabilities and limits of the underlying framework, we identified key issues of the prototype. A new implementation addresses these obstacles while keeping the overall application logic and usability. This leads to a trial-ready mobile patient questionnaire system.


Correlation of pre-operative planning to surgical correction of opening wedge HTO: a radiographic study utilizing a manual measurement method.
High tibial osteotomy (HTO) utilizing a medial opening wedge has become a common and effective surgical technique for treatment of isolated medial compartment knee osteoarthritis secondary to varus malalignment. To reduce the risk of under- or overcorrection, accurate preoperative planning is important. This is a radiographic study to evaluate the reliability of preoperative measurement on full-length weight-bearing X-rays (FLWBXr) compared to post-operative X-rays after healing. In addition, we calculated if the intraoperative opening wedge performed was consistent with the preoperative calculation and the postoperative correction. Three independent observers measured preoperative and postoperative FLWBXr at three different times. The angle of varus deformity; the angle to correct and the wedge needed to achieve desired alignment: the angle achieved postoperatively, and the postoperative mechanical axis deviation were measured. Intra- and inter-rater reliability showed high values for all the investigated parameters. The discrepancy between the calculated wedge and the wedge actually used in surgery ranged from 1 mm of over-correction to 3 mm of undercorrection, averaging -1.3 mm. The mechanical axis crossed the tibial plateau an average of 53% ±12.7. Clustering the data by the plate type statistically significant differences were found for preoperative varus alignment, advocated correction, intraoperative correction and post-op alignment. The Dugdale method can be considered highly reliable. Possible factors affecting the final correction are: surgeon's desire not to overcorrect in young patients and minimal osteoarthritis; measurement errors; variability in the method the FLWBXr is performed. In addition, the under correction could be the result of some collapse with time or the correction could be affected by the fixation system. Further investigation should include complete post-operative evaluation of outcomes and assess the role of these potential factors and their relationship to correction. Level of Evidence: Level III, Retrospective study.


An active bubble trap and debubbler for microfluidic systems.
We present a novel, fully integrated microfluidic bubble trap and debubbler. The 2-layer structure, based on a PDMS valve design, utilizes a featured membrane to stop bubble progression through the device. A pneumatic chamber directly above the trap is evacuated, and the bubble is pulled out through the gas-permeable PDMS membrane. Normal device operation, including continuous flow at atmospheric pressure, is maintained during the entire trapping and debubbling process. We present a range of trap sizes, from 2 to 10 mm diameter, and can trap and remove bubbles up to 25 microL in under 3 h.


Laminin 5 expression in metaplastic breast carcinomas.
Metaplastic carcinoma of the breast shows squamous, sarcomatous, or chondromatous differentiation and has a poor prognosis. Laminin 5 is a heterotrimer of alpha3, beta3, and gamma(2) [corrected] chains and induces aggressive properties in cancer cells including motility, invasion, and epithelial to mesenchymal transition. Twenty-five cases included 7 squamous, 4 sarcomatous, 8 chondroid, 1 fibromatosislike metaplastic carcinomas, and 5 cases with 2 metaplastic components. Tumors were stained with laminin 5-specific beta3 and gamma(2) [corrected] chain, p63, and cytokeratin 5/6 (CK 5/6) antibodies. All 4 antibodies stained normal myoepithelium. Both laminin 5 antibodies stained 24/25 (96%) of the tumors, with an identical distribution of the 2 chains in 87.5% of the positively staining cases. In contrast, p63 and CK 5/6 stained 68% and 64% of the tumors, respectively. By comparison, only 16% of high-grade carcinoma controls stained for laminin 5. Similar to the metaplastic carcinomas, all 12 triple negative tumors, those negative for estrogen receptor, progesterone receptor, and Her2/neu, expressed laminin 5. None of 4 breast sarcomas stained for either of the laminin 5 chains or CK 5/6, but 1 (25%) stained for p63. Laminin 5 expression in metaplastic and other basal-like carcinomas is of interest for several reasons. First, these data provide additional evidence of the myoepithelial and basal-like phenotype of these carcinomas. Second, these are the only breast carcinoma subtypes to demonstrate laminin 5 staining in a large proportion of cases. Third, expression of laminin 5 in metaplastic carcinomas may suggest a mechanism for their increased aggressiveness and epithelial to mesenchymal transition phenotype. Finally, compared with other myoepithelial markers, laminin 5 is more sensitive than those previously published. Thus laminin 5 may be helpful for making the diagnosis of metaplastic carcinomas in biopsies, allowing the potential for aggressive early treatment. Further study of other basal-like tumors for laminin 5 expression is warranted to determine the usefulness of laminin 5 in their diagnosis.


Identification of seven surface-exposed Brucella outer membrane proteins by use of monoclonal antibodies: immunogold labeling for electron microscopy and enzyme-linked immunosorbent assay.
A panel of monoclonal antibodies (MAbs) to seven Brucella outer membrane proteins were characterized. These antibodies were obtained by immunizing mice with sodium dodecyl sulfate-insoluble (SDS-I) fractions, cell walls, or whole bacterial cells of Brucella abortus or B. melitensis. Enzyme-linked immunosorbent assays were used to screen the hybridoma supernatants and to determine their binding at the surface of rough and smooth B. abortus and B. melitensis cells. The outer membrane proteins (OMPs) recognized by these antibodies were the proteins with molecular masses of 25 to 27 kDa and 36 to 38 kDa (porin) (major proteins) and the proteins with molecular masses of 10, 16.5, 19, 31 to 34, and 89 kDa (minor proteins). Surface exposure of these OMPs was visualized by electron microscopy by using the MAbs and immunogold labeling. Binding of the MAbs on whole rough bacterial cells indicates that the 10-, 16.5-, 19-, 25- to 27-, 31- to 34-, 36- to 38-, and 89-kDa OMPs are exposed at the cell surface. However, enzyme-linked immunosorbent assay results indicate a much better binding of the anti-OMP MAbs on rough strains than on the corresponding smooth strains except for the anti-19-kDa MAb. Immunoelectron microscopy showed that on smooth B. abortus cells only the 89- and 31- to 34-kDa OMPs were not accessible to the MAbs tested. Binding of the anti-31- to 34-kDa MAb at the cell surface was observed for the rough B. abortus cells and for the rough and smooth B. melitensis cells. These results indicate the importance of steric hindrance due to the presence of the long lipopolysaccharide O side chains in the accessibility of OMPs on smooth Brucella strains and should be considered when undertaking vaccine development.


The population genomics of multiple tsetse fly (Glossina fuscipes fuscipes) admixture zones in Uganda.
Understanding the mechanisms that enforce, maintain or reverse the process of speciation is an important challenge in evolutionary biology. This study investigates the patterns of divergence and discusses the processes that form and maintain divergent lineages of the tsetse fly Glossina fuscipes fuscipes in Uganda. We sampled 251 flies from 18 sites spanning known genetic lineages and the four admixture zones between them. We apply population genomics, hybrid zone and approximate Bayesian computation to the analysis of three types of genetic markers: 55,267 double-digest restriction site-associated DNA (ddRAD) SNPs to assess genome-wide admixture, 16 microsatellites to provide continuity with published data and accurate biogeographic modelling, and a 491-bp fragment of mitochondrial cytochrome oxidase I and II to infer maternal inheritance patterns. Admixture zones correspond with regions impacted by the reorganization of Uganda's river networks that occurred during the formation of the West African Rift system over the last several hundred thousand years. Because tsetse fly population distributions are defined by rivers, admixture zones likely represent both old and new regions of secondary contact. Our results indicate that older hybrid zones contain mostly parental types, while younger zones contain variable hybrid types resulting from multiple generations of interbreeding. These findings suggest that reproductive barriers are nearly complete in the older admixture zones, while nearly absent in the younger admixture zones. Findings are consistent with predictions of hybrid zone theory: Populations in zones of secondary contact transition rapidly from early to late stages of speciation or collapse all together.


Pancreatic enzyme products: digesting the changes.
To review the pharmacology, dosage regimens, efficacy, and safety of currently marketed pancreatic enzyme products (PEPs). Studies were identified by PubMed (1966-January 2011), clinicaltrials.gov, fda.gov, and International Pharmaceutical Abstracts. Search terms included pancreatic enzyme, lipase, Creon, Zenpep, Pancreaze, and exocrine pancreatic insufficiency (EPI). All human studies evaluating the efficacy of currently approved or potential PEPs were reviewed. PEPs are composed of porcine lipase, amylase, and protease and are used in patients with EPI secondary to cystic fibrosis, chronic pancreatitis, and pancreatectomy. In 1938, PEPs were exempted from the Food, Drug, and Cosmetic Act of 1938 and never underwent a formal Food and Drug Administration (FDA) review process. In response to reports of treatment failures during product interchange, the FDA conducted a review of available PEP products. This review found a large variability of response between the unapproved PEP products, which resulted in the FDA requiring approval of all PEP products by April 2010. The 3 delayed-release, enteric-coated PEPs currently approved by the FDA (Creon, Zenpep, and Pancreaze) have demonstrated efficacy and safety in EPI secondary to cystic fibrosis. Creon has also demonstrated safety and efficacy in EPI secondary to chronic pancreatitis and pancreatectomy. Cost difference between the 3 products is minimal. Treatment-related adverse events in clinical studies for all PEPs were less than or similar to those with placebo. At this time, Creon is an appropriate first-line agent, as it has been approved for chronic pancreatitis, pancreatectomy, and cystic fibrosis.