Design of a Gough-Stewart Platform Based on Visual Servoing Controller.
Designing a robot with the best accuracy is always an attractive research direction in the robotics community. In order to create a Gough-Stewart platform with guaranteed accuracy performance for a dedicated controller, this paper describes a novel advanced optimal design methodology: control-based design methodology. This advanced optimal design method considers the controller positioning accuracy in the design process for getting the optimal geometric parameters of the robot. In this paper, three types of visual servoing controllers are applied to control the motions of the Gough-Stewart platform: leg-direction-based visual servoing, line-based visual servoing, and image moment visual servoing. Depending on these controllers, the positioning error models considering the camera observation error together with the controller singularities are analyzed. In the next step, the optimization problems are formulated in order to get the optimal geometric parameters of the robot and the placement of the camera for the Gough-Stewart platform for each type of controller. Then, we perform co-simulations on the three optimized Gough-Stewart platforms in order to test the positioning accuracy and the robustness with respect to the manufacturing errors. It turns out that the optimal control-based design methodology helps get both the optimum design parameters of the robot and the performance of the controller {robot + dedicated controller}.


Glycosylated hemoglobin in diabetic and nondiabetic dogs.
Glycosylated hemoglobin (HbA1) was measured in 40 nondiabetic hospitalized dogs, 16 clinically normal laboratory colony dogs, and 16 diabetic dogs. Mean HbA1 values (% of total Hb) for the 3 groups were 6.43, 5.62, and 9.63, respectively. The mean values for the 2 nondiabetic groups differed significantly (P less than 0.05), and the mean values for the nondiabetic dogs were significantly lower than the mean value for that of the diabetic dogs (P less than 0.001). Fifteen of 16 diabetic dogs had HbA1 concentrations greater than 7.5%. These results suggested that HbA1 measurement may be valuable for monitoring effectiveness of therapy in canine diabetes mellitus.


Follow-up compliance in febrile children: a comparison of two systems.
Follow-up compliance is critical in febrile children because they may harbor unrecognized life-threatening illnesses. This study compares follow-up rates between 2 systems: Wilford Hall Medical Center (WHMC), with preset appointments after ED release, and free medical care; and Fairfax Hospital (FFX), where parents must arrange follow-up appointments after ED release, and are responsible for payment for their follow-up visits. The study also investigated factors associated with follow-up compliance. This was a prospective, observational study of febrile children seen in 2 EDs with different systems for patient follow-up. From ED records and parental phone calls, diagnosis, follow-up compliance, and demographics were collected. Data were analyzed using logistic regression and chi2. 423 children met entrance criteria, and 330 parents were successfully contacted after the child's ED release (146 from WHMC; 184 from FFX). The WHMC children were more likely to comply with follow-up than were the children in the FFX system (92% vs 67% follow-up, odds ratio 2.5, 95% CI 1.1-5.3). Other factors associated with noncompliance with recommended follow-up were: Hispanic ethnicity, non-English-speaking parents, and follow-up suggested for >24 hours after ED release. For FFX, self-pay, lack of a follow-up physician, parents' dissatisfaction with the ED medical care, and diagnosis of otitis media were also significant factors found associated with noncompliance. Febrile children evaluated in a medical system with prearranged follow-up appointments and free medical care are more likely to comply with recommended follow-up than are those evaluated in a system where payment and appointments are the responsibility of the parents. Efforts should be made to improve follow-up compliance by modeling the WHMC system.


Novel antioxidant peptides from fermented mushroom Ganoderma lucidum.
Oxidative stress has been linked with the pathogenesis of many human diseases including cancer, aging, and atherosclerosis. The present study investigates the antioxidant activities of peptides isolated from the medicinal mushroom, Ganoderma lucidum. G. lucidum has been shown to possess potent antioxidant activity with little or no side effects. Polysaccharide, polysaccharide-peptide complex, and phenolic components of G. lucidum have been proposed to be responsible for this antioxidant effect. However, research has shown that the G. lucidum peptide (GLP) is the major antioxidant component of G. lucidum. The objective of this study was to evaluate the antioxidant activity of this peptide using different oxidation systems. GLP showed potent antioxidant activities in both lightproof soybean oil and lard systems, assessed by lipid peroxidant value. Compared to butylated hydroxytoluene, GLP showed a higher antioxidant activity in the soybean oil system. Soybean lipoxygenase activity was blocked by GLP in a dose-dependent manner with an IC50 value of 27.1 microg/mL. GLP showed scavenging activity toward hydroxyl radicals produced in a deoxyribose system with an IC50 value of 25 microg/mL, and GLP effectively quenched superoxide radical anion produced by pyrogallol autoxidation in a dose-dependent manner. Malondialdehyde level has been used as the oxidation index in many biological systems. GLP showed substantial antioxidant activity in the rat liver tissue homogenates and mitochondrial membrane peroxidation systems. The auto-hemolysis of rat red blood cells was also blocked by GLP in a dose-dependent manner. On the basis of these results, it is concluded that GLP is the major constituent responsible for the antioxidant activity of G. lucidum. GLP could play an important role in the inhibition of lipid peroxidation in biological systems through its antioxidant, metal chelating, and free radical scavenging activities.


Influence of sex on propofol metabolism, a pilot study: implications for propofol anesthesia.
The basis of high intersubject variability of propofol metabolism is unclear. Therefore, we examined the influence of genetic polymorphisms of the key metabolizing enzymes cytochrome P450 2B6 (CYP2B6) and uridine diphosphate (UDP)-glucuronosyltransferase 1A9 (UGT1A9), age, and sex on propofol biotransformation in vitro and in vivo. Plasma concentrations of propofol, 4-hydroxypropofol, and their glucuronides were measured over 20 min in 105 patients after a single intravenous bolus of propofol. Propofol 4-hydroxylation activity, genotypes, and content of CYP2B6 protein in 68 human livers were determined. The common single nucleotide polymorphisms (SNPs) for the CYP2B6 and UGT1A9 genes were analyzed by polymerase chain reaction (PCR). Plasma levels of propofol metabolites showed high interindividual variability (range of coefficient of variation 89-128%). This was supported by in vitro data showing similar variability of propofol 4-hydroxylation in liver microsomes and 1.9-fold higher CYP2B6 protein content in the livers from women. No significant relationships were revealed between the SNPs studied and propofol metabolism. However, patients' sex had a pronounced effect on propofol metabolism. Thus, women had higher amounts of propofol glucuronide (1.25-fold; p = 0.03), 4-hydroxypropofol-1-glucuronide (2.1-fold; p = 0.0009), and 4-hydroxypropofol-4-glucuronide (1.7-fold; p = 0.02) as shown by the weight-corrected area under the time-plasma concentration curve of metabolites. Additionally, the sexual dimorphism in 4-hydroxypropofol glucuronidation was prominent in the 35- to 64-year-old subgroup. No significant effects of CYP2B6 and UGT1A9 SNPs or age on propofol metabolism were revealed in this pilot study, but there was a pronounced effect of sex, a finding that indicates an important factor for the previously described sex difference in systemic clearance of propofol seen.


Respiratory Sinus Arrhythmia Moderates the Relation between Parent-Adolescent Relationship Quality and Adolescents' Social Adjustment.
This 2-wave longitudinal study aimed (1) to investigate whether high resting RSA predicted adolescents' lower externalizing behavior and higher empathic concern, and (2) to address the potential moderating role of resting RSA in the association between parent-adolescent relationship quality and adolescents' externalizing behavior and empathic concern. In a sample of 379 adolescents (212 boys, 167 girls), resting RSA was assessed during a laboratory session, and adolescents reported on parental support, negative interaction with parents, empathic concern and externalizing behavior during a home visit. We found no support for high resting RSA predicting low externalizing behavior or high empathic concern. However, in line with our hypotheses, we did find several instances of RSA functioning as a moderator, although the interaction patterns varied. First, negative interaction with parents was a negative predictor of externalizing behavior for girls low in resting RSA, whereas the association was non-significant for girls with high RSA. Second, higher negative interaction with parents predicted lower empathic concern for boys high in resting RSA, whereas the association was reversed for boys with low resting RSA. Third, parental support was a positive predictor of empathic concern for girls high in resting RSA, whereas the association was non-significant for girls low in resting RSA. The findings suggest that adolescents with different levels of resting RSA respond differentially to relationship quality with parents.


Ultrafast X-ray Scattering from Molecules.
We present a theoretical framework for the analysis of ultrafast X-ray scattering experiments using nonadiabatic quantum molecular dynamics simulations of photochemical dynamics. A detailed simulation of a pump-probe experiment in ethylene is used to examine the sensitivity of the scattering signal to simulation parameters. The results are robust with respect to the number of wavepackets included in the total expansion of the molecular wave function. Overall, the calculated scattering signals correlate closely with the dynamics of the molecule.


3D Culture Facilitates VEGF-Stimulated Endothelial Differentiation of Adipose-Derived Stem Cells.
De novo vascularization of implantable tissue and whole organ constructs has been a significant challenge in the field of tissue engineering; the use of endothelial cell populations for this task is constrained by the cell population's limited regeneration capacity and potential for loss of function. Thus, there is a need for a stem-cell population that may be induced into an endothelial cell phenotype reliably. Adipose derived stem cells (ADSCs) are multipotent cells that can be readily isolated from donor fat and may have the potential to be readily induced into endothelial cells. The ability to stimulate endothelial differentiation of these cells has been limited in standard 2D culture. We hypothesized that 3D culture would yield better differentiation. To study the influence of cell density and culture conditions on the potential of ADSCs to differentiate into an endothelial-like state, we seeded these cells types within a 3D cell-adhesive, proteolytically degradable, peptide-modified poly(ethylene-glycol) (PEG) hydrogel. ADSCs were either cultured in basal media or pro-angiogenic media supplemented with 20 ng/mL of VEGF in 2D and then encapsulated at low or high densities within the PEG-based hydrogel. These encapsulated cells were maintained in either basal media or pro-angiogenic media. Cells were then isolated from the hydrogels and cultured in Matrigel to assess the potential for tubule formation. Our work shows that maintenance of ADSCs in a pro-angiogenic medium in 2D monoculture alone does not result in any CD31 expression. Furthermore, the level of CD31 expression was affected by the density of the cells encapsulated within the PEG-based hydrogel. Upon isolation of these cells, we found that these induced ADSCs were able to form tubules within Matrigel, indicative of endothelial function, while ADSCs cultured in basal medium could not. This finding points to the potential for this stem-cell population to serve as a safe and reliable source of endothelial cells for tissue engineering and regenerative medicine purposes.


The metabolic effects of lopinavir/ritonavir in HIV-negative men.
Therapy with HIV protease inhibitors (PI) has been shown to worsen glucose and lipid metabolism, but whether these changes are caused by direct drug effects, changes in disease status, or body composition is unclear. Therefore, we tested the effects of the PI combination lopinavir and ritonavir on glucose and lipid metabolism in HIV-negative subjects. A dose of 400 mg lopinavir/100 mg ritonavir was given twice a day to 10 HIV-negative men. Fasting glucose and insulin, lipid and lipoprotein profiles, oral glucose tolerance, insulin sensitivity by euglycemic hyperinsulinemic clamp, and body composition were determined before and after lopinavir/ritonavir treatment for 4 weeks. On lopinavir/ritonavir, there was an increase in fasting triglyceride (0.89 +/- 0.15 versus 1.63 +/- 0.36 mmol/l; P = 0.007), free fatty acid (FFA; 0.33 +/- 0.04 versus 0.43 +/- 0.06 mmol/l; P = 0.001), and VLDL cholesterol (15.1 +/- 2.6 versus 20 +/- 3.3 mg/dl; P = 0.05) levels. There were no changes in fasting LDL, HDL, IDL, lipoprotein (a), or total cholesterol levels. Fasting glucose, insulin, and insulin-mediated glucose disposal were unchanged, but on a 2 h oral glucose tolerance test glucose and insulin increased. There were no changes in weight, body fat, or abdominal adipose tissue by computed tomography. Treatment with 4 weeks of lopinavir/ritonavir in HIV-negative men causes an increase in triglyceride levels, VLDL cholesterol, and FFA levels. Lopinavir/ritonavir leads to a deterioration in glucose tolerance at 2 h, but there is no significant change in insulin-mediated glucose disposal rate by euglycemic hyperinsulinemic clamp.


Potential Use of Phenolic Acids as Anti-Candida Agents: A Review.
There has been a sharp rise in the occurrence of Candida infections and associated mortality over the last few years, due to the growing body of immunocompromised population. Limited number of currently available antifungal agents, undesirable side effects and toxicity, as well as emergence of resistant strains pose a considerable clinical challenge for the treatment of candidiasis. Therefore, molecules that derived from natural sources exhibiting considerable antifungal properties are a promising source for the development of novel anti-candidal therapy. Phenolic compounds isolated from natural sources possess antifungal properties of interest. Particularly, phenolic acids have shown promising in vitro and in vivo activity against Candida species. However, studies on their mechanism of action alone or in synergism with known antifungals are still scarce. This review attempts to discuss the potential use, proposed mechanisms of action and limitations of the phenolic acids in anti-candidal therapy.


Procedure-Associated Costs and Mid-Term Outcomes of Endovascular Zone 0 and Zone 1 Aortic Arch Repair.
Thoracic endovascular aortic repair (TEVAR) of proximal aortic arch pathology provides a less-invasive treatment option for high-risk patients ineligible for open arch reconstruction. However, the fiscal impact of these techniques remains unclear. Therefore, our objective was to characterize the mid-term outcomes after Zone 0 and Zone 1 TEVAR and describe the associated technical costs, revenues, and net margins at a single tertiary medical center. We examined all patients who underwent TEVAR between April 2011 and August 2019 via retrospective chart review. Patients were categorized by proximal endograft extent to identify Zone 0 or Zone 1 repairs. Procedural characteristics and outcomes were described. Technical costs, revenues, and margins were obtained from the hospital finance department. We identified 10 patients (6 Zone 0, 4 Zone 1) who were denied open arch reconstruction. Patients were predominantly female (n = 8; 80%) and the mean age was 72.8 ± 5.5 years. TEVAR was performed in 5 asymptomatic patients, urgently in 3 symptomatic patients, and emergently in 2 ruptured patients. TEVAR plus extra-anatomic bypass was performed in 4 patients. Another 4 patients also received parallel stent-grafting while 1 patient received a branched thoracic endograft and yet another an in-situ laser fenestration followed by branch stent grafting. Within the 30-day postoperative period, 1 patient experienced stroke and 1 patient died. Bypass and branch vessel patency were 100% through the duration of follow-up (mean 19.3 months). Mean total technical cost associated with all procedures or repair stages was $105,164 ± $59,338 while mean net technical margin was -$25,055 ± $18,746. The net technical margin was negative for 9 patients. Endovascular repair of the proximal aortic arch is associated with good mid-term outcomes in patients considered too high-risk for open repair. However, reimbursement does not adequately cover treatment cost, with net technical margins being negative in nearly all cases. To remain financially sustainable, efforts should be made to both optimize aortic arch TEVAR delivery as well as advocate for reimbursement commensurate with associated costs.


Medical subinternship: student experience on a resident uncovered hospitalist service.
Studies demonstrating the value of hospitalists to medical student education have been performed in traditional resident covered ward service settings (RCWS). To compare medical subinterns' experiences on an RCWS to that on a resident uncovered hospitalist service (RUHS). We assessed students' overall experience and knowledge learned on the two services using a 5-point Likert scale. We also assessed learning environment characteristics, workload, and time spent at the hospital on each service. The mean rating for knowledge learned was higher on the RCWS. Subinterns rated the two services equivalent on measures of educational value of patient problems, faculty assessment, supervision, and number and value of teaching sessions. The RCWS received higher ratings on variety of patient problems and frequency of intellectual discussion. The RCWS provided a superior learning experience for subinterns. Academic medical centers should take these findings into consideration before placing medical students on an RUHS.


Tumorigenic potential of a recombinant retrovirus containing sequences from Moloney murine leukemia virus and feline leukemia virus.
A recombinant retrovirus, termed MoFe2-MuLV, was constructed in which the U3 region of T-lymphomagenic Moloney murine leukemia virus (Mo-MuLV) was replaced by that of FeLV-945, a provirus of unique long terminal repeat (LTR) structure identified only in non-T-cell, non-B-cell lymphomas of the domestic cat. The LTR of FeLV-945 is unusual in that it contains only a single copy of the transcriptional enhancer followed 25 bp downstream by a 21-bp sequence in triplicate in tandem. Infectivity of MoFe2-MuLV was demonstrated in vitro in SC-1 cells and in vivo in neonatal NIH-Swiss mice. Tumors occurred in MoFe2-MuLV-infected animals following a latency period of 4 to 10 months (average, 6 months). The results of Southern blot analysis of the T-cell receptor beta locus demonstrated that all tumors were lymphomas of T-cell origin. MoFe2-MuLV LTRs were amplified by PCR from tumor DNA and were characterized by nucleotide sequence analysis. LTRs from the tumors that occurred with relatively shorter latency predominantly retained the original MoFe2-MuLV sequence intact and unaltered. Tumors that occurred with relatively longer latency contained LTRs that also retained the 21-bp sequence triplication characteristic of the original virus but had acquired various duplications of enhancer sequences. The repeated identification of enhancer duplications in late-appearing tumors suggests that the duplication affords a selective advantage, although apparently not in the efficient induction of T-cell lymphoma. Proto-oncogenes known to be targets of insertional mutagenesis in the majority of Mo-MuLV-induced tumors or in feline non-T-cell, non-B-cell lymphomas were shown not to be rearranged in any tumor examined. Mink cell focus-inducing (MCF) proviral DNA was readily detectable in some, but not all, tumors. The presence or absence of MCF did not correlate with the kinetics of tumor induction. These studies indicate that the single-enhancer, triplication-containing FeLV LTR, typical of non-T-cell, non-B-cell lymphomas in cats, is competent in the induction of T-cell lymphoma in mice. The findings suggest that the mechanism of MoFe2-MuLV-mediated lymphomagenesis may differ from that of Mo-MuLV-mediated disease, considering the possible involvement of novel oncogenes and the variable presence of MCF recombinants.


Utilization of a thermosensitive episome bearing transposon TN10 to isolate Hfr donor strains of Erwinia carotovora subsp. chrysanthemi.
A thermosensitive episome bearing the transposon Tn10, F(Ts)::Tn10 Lac+, has been successfully transferred from Escherichia coli to several wild strains of the enterobacteria Erwinia carotovora subsp. chrysanthemi, which are pathogenic on Saintpaulia ionantha. In one of these strains, all of the characters controlled by this episome (Lac+, Tetr, Tra+) were expressed, and its replication was stopped at 40 degrees C and above. At 30 degrees C, the episome was easily transferred between strains derived from E. carotovora subsp. chrysanthemi 3937j and to E coli. Hfr donor strains were obtained from a F' strain of 3937j by selecting clones which grew at 40 degrees C on plates containing tetracycline. One of these strains, Hfrq, was examined in more detail: the characters Lac+ and Tetr were stabilized and did not segregate higher than its parental F' strain. The mating was most efficient at 37 degrees C on a membrane. Hfrq transferred its chromosome to recipient strains at high frequency and in a polarized fashion, as evidenced by the gradient of transfer frequencies, the kinetics of marker entry (in interrupted mating experiments), and the analysis of linkage between different markers. The chromosome of Hfrq was most probably transferred in the following sequence: origin...met...xyl...arg...ile...leu...thr...cys...pan...ura...gal...trp...his. ..pur... Moreover, this genetic transfer system proved to be efficient in strain construction.


Using a Model of Germ-Free Animals to Study the Impact of Gut Microbiome in Research: A Step by Step Sterility Setting and Management.
The particularly unique composition of the gut microbiota has the potential to influence the health or disease status of animal and human hosts. Altering the homeostasis of the host-bacteria could lead to changes in gut flora that result in disease or activation of a specific immunological response, which could explain the variations observed in patient responses to current therapies. A standardized model is crucial for studying the influence of the gut microbiota on therapeutic modalities. A step by step mouse model and sterility management system that compares a control strain of C57BL/6 mice to the established C57BL/6 germ-free (GF) strain has been developed. The GF BL/6 mouse phenotype is well established, and the anatomical differences between the GF and control mice were evident in this model. This method could be applied to research studies investigating the microbiome impact, the response to various therapies, or disease transfer via fecal transplants. A standardized sterility maintenance method is crucial in this context.


[Practical advice for travellers with immune disorders].
For patients with immune disorders, the risk of infection during travel depends on the cause and severity of the immune disorder and the type of travel. Immunocompromised travellers experience more severe effects of illness than those without immune disorders. Some risks can be reduced or avoided by taking adequate precautions and, in some cases, modifying travel plans. Ensuring adequate medication use during the trip requires careful planning prior to travel. Regarding vaccination, immunocompromised travellers may have an impaired ability to generate antibodies; live attenuated vaccines are often contraindicated. The treating physician must take a proactive role when an immunocompromised patient indicates that he or she plans to travel. Protocols developed by the Dutch National Coordination Centre for Travellers Health (LCR) provide practical advice regarding a number of situations. Provided that they are given proper individualised advice, there is little concrete evidence to suggest that these patients should not travel anywhere they wish.


Effect of bile and desoxycholate on gram-negative anaerobic bacteria.
The bile tests for characterizing gram-negative anaerobic bacilli were reevaluated in prereduced anaerobically sterilized peptone-yeast-glucose broth, in thioglycollate broth, and on blood agar plates. Blood agar plates were unsatisfactory. The combination of 20% bile with 0.1% desoxycholate inhibited Fusobacterium, Bacteroides melaninogenicus, and B. oralis and sometimes Sphaerophorus necrophorus, but not B. fragilis or other Sphaerophorus species studied. Ten per cent bile with 0.05% desoxycholate was less satisfactory. There was no significant difference between fresh and commercial powdered bile. Desoxycholate (0.1% in thioglycollate broth) inhibited B. fragilis, Fusobacterium, B. melaninogenicus, B. oralis, and S. necrophorus, but not S. varius or S. mortiferus/S. ridiculosus. The bile and desoxycholate tests are simple to perform and helpful for characterization and classification of gram-negative anaerobic bacilli.


Feasibility of a home-based computerized cognitive training for pediatric patients with congenital or acquired brain damage: An explorative study.
Pediatric brain damage is associated with various cognitive deficits. Cognitive rehabilitation may prevent and reduce cognitive impairment. In recent years, home-based computerized cognitive training (CCT) has been introduced in clinical practice to increase treatment opportunities for patients (telerehabilitation). However, limited research has been conducted thus far on investigating the effects of remote CCT for the juvenile population in contexts other than English-speaking countries. The aim of the present study was to investigate the feasibility of a home-based CCT in a group of Italian adolescents with brain damage. A commercially available CCT (Lumosity) developed in the English language was used due to the lack of telerehabilitation programs in the Italian language that allow stimulation of multiple cognitive domains and, at the same time, remote automatic collection of data. Thus, this investigation provides information on the possibility of introducing CCT programs available in foreign languages in countries with limited investment in the telerehabilitation field. 32 adolescents aged 11-16 with a diagnosis of congenital or acquired (either traumatic or non-traumatic) brain damage participated in the study. They received 40 training sessions (5 days/week for 8 weeks). Before starting the training program, they received face-to-face demonstration of training exercises and written instructions in their mother tongue. The feasibility of both training and study design and procedures was assessed through 9 criteria taken from extant literature. All 9 feasibility criteria were met. 31 out of the 32 participants demonstrated adherence to the training program. 94.2% of training sessions were completed in the recommended timeframe. No significant technical issue was found. Telerehabilitation seems to be a feasible practice for adolescents with brain damage. A training program developed in a foreign language can be used to counter the unavailability of programs in patients' mother tongue. The trial is registered with the ISRCTN registry with study ID ISRCTN59250807.


CD151 regulates tumorigenesis by modulating the communication between tumor cells and endothelium.
The tetraspanin CD151 forms stoichiometric complexes with laminin-binding integrins (e.g., alpha3beta1, alpha6beta1, and alpha6beta4) and regulates their ligand-binding and signaling functions. We have found that high expression of CD151 in breast cancers is associated with decreased overall survival (3.44-fold higher risk of death). Five-year estimated survival rates were 45.8% (95% confidence interval, 16.4-71.4%) for CD151-positive patients and 79.9% (95% confidence interval, 62.2-90.0%) for CD151-negative patients. Furthermore, CD151 was positively associated with axillary lymph node involvement. To study the biological significance of this observation, we investigated the contribution of CD151 in breast cancer tumorigenesis using MDA-MB-231 cells as a model system. Stable down-regulation of this tetraspanin by short-hairpin RNA decreased the tumorigenicity of these cells in mice. Detailed immunohistologic analysis of CD151(+) and CD151(-) xenografts showed differences in tumor vascular pattern. Vascularization observed at the subcutaneous border of the CD151(+) tumors was less pronounced or absent in the CD151(-) xenografts. In vitro experiments have established that depletion of CD151 did not affect the inherent proliferative capacity of breast cancer cells in three-dimensional extracellular matrices, but modified their responses to endothelial cells in coculture experiments. The modulatory activity of CD151 was dependent on its association with both alpha3beta1 and alpha6beta4 integrins. These data point to a new role of CD151 in tumorigenesis, whereby it functions as an important regulator of communication between tumor cells and endothelial cells. These results also identify CD151 as a potentially novel prognostic marker and target for therapy in breast cancer.


Using Web-Based Pin-Drop Maps to Capture Activity Spaces Among Young Adults Who Use Drugs in Rural Areas: Cross-Sectional Survey.
Epicenters of harmful drug use are expanding to US rural areas, with rural young adults bearing a disproportionate burden. A large body of work suggests that place characteristics (eg, spatial access to health services) shape vulnerability to drug-related harms among urban residents. Research on the role of place characteristics in shaping these harms among rural residents is nascent, as are methods of gathering place-based data. We (1) analyzed whether young rural adults who used drugs answered self-administered Web-based mapping items about locations where they engaged in risk behaviors and (2) determined the precision of mapped locations. Eligible individuals had to report recently using opioids to get high; be aged between 18 and 35 years; and live in the 5-county rural Appalachian Kentucky study area. We used targeted outreach and peer-referral methods to recruit participants. The survey asked participants to drop a pin in interactive maps to mark where they completed the survey, and where they had slept most; used drugs most; and had sex most in the past 6 months. Precision was assessed by (1) determining whether mapped locations were within 100 m of a structure and (2) calculating the Euclidean distance between the pin-drop home location and the street address where participants reported sleeping most often. Measures of central tendency and dispersion were calculated for all variables; distributions of missingness for mapping items and for the Euclidean distance variable were explored across participant characteristics. Of the 151 participants, 88.7% (134/151) completed all mapping items, and ≥92.1% (>139/151) dropped a pin at each of the 4 locations queried. Missingness did not vary across most participant characteristics, except that lower percentages of full-time workers and peer-recruited participants mapped some locations. Two-thirds of the pin-drop sex and drug use locations were less than 100 m from a structure, as were 92.1% (139/151) of pin-drop home locations. The median distance between the pin-drop and street-address home locations was 2.0 miles (25th percentile=0.8 miles; 75th percentile=5.5 miles); distances were shorter for high-school graduates, staff-recruited participants, and participants reporting no technical difficulties completing the survey. Missingness for mapping items was low and unlikely to introduce bias, given that it varied across few participant characteristics. Precision results were mixed. In a rural study area of 1378 square miles, most pin-drop home addresses were near a structure; it is unsurprising that fewer drug and sex locations were near structures because most participants reported engaging in these activities outside at times. The error in pin-drop home locations, however, might be too large for some purposes. We offer several recommendations to strengthen future research, including gathering metadata on the extent to which participants zoom in on each map and recruiting participants via trusted staff.


Influence of molecular rebinding on the reaction rate of complex formation.
We simulated Brownian diffusion and reaction-diffusion processes to study the influence of molecular rebinding on the reaction rates of bimolecular reactions. We found that the number of rebinding events, Nreb, is proportional to the target's size and inversely proportional to the diffusion coefficient D and simulation time-step Δt. We found the proportionality constant close to π-1/2. We confirmed that Nreb is defined as a ratio of the activation-limited rate constant ka to the diffusion-limited rate constant, kD. We provide the formula describing the reactivity coefficient κ, modelling the transient-native complex transition for the activation-controlled reaction rates. We show that κ is proportional to (D/Δt)1/2. Finally, we apply our rebinding-including reaction rate model to the real reactions of photoacid dissociation and protein association. Based on literature data for both types of reactions, we found the Δt time-scale. We show that for the photodissociation of a proton, the Δt is equal to 171 ± 18 fs and the average number of rebinding events is approximately equal to 40. For proteins, Δt is of the order of 100 ps with around 20 rebinding events. In both cases the timescale is similar to the timescale of fluctuation of the solvent molecules surrounding the reactants; vibrations and bending in the case of photoacid dissociation and diffusional motion for proteins.


Indomethacin-induced reduction in CRTH2 in eosinophilic pustular folliculitis (Ofuji's disease): a proposed mechanism of action.
Eosinophilic pustular folliculitis is an inflammatory skin disease characterized by pruritic follicular papulopustules. It is usually resistant to topical and/or systemic corticosteroids, but it responds well to systemic indomethacin. We report here two patients with classical-type disease who were treated with systemic indomethacin. As indomethacin is an inhibitor of cyclo-oxygenases and a potent agonist of the prostaglandin D2 (PGD2) receptor, CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cells), we investigated the effects of indomethacin on CRTH2 expression by leukocytes. CRTH2 was expressed on blood eosinophils and lymphocytes. In vitro treatment with indomethacin suppressed the expression of CRTH2 on these cells. In addition, systemic treatment with indomethacin reduced eosinophil CRTH2 expression in another patient in association with improvement of skin lesions and blood eosinophilia. A number of inflammatory cells expressed haematopoietic PGD synthase, an essential enzyme for generating PGD2 in skin lesions of eosinophilic pustular folliculitis. A PGD2-CRTH2 interaction may be involved in the pathogenesis. Moreover, indomethacin may exert its therapeutic effect via reducing CRTH2 expression, as well as by inhibiting PGD2 synthesis.


Differences in the cognitive skills of bonobos and chimpanzees.
While bonobos and chimpanzees are both genetically and behaviorally very similar, they also differ in significant ways. Bonobos are more cautious and socially tolerant while chimpanzees are more dependent on extractive foraging, which requires tools. The similarities suggest the two species should be cognitively similar while the behavioral differences predict where the two species should differ cognitively. We compared both species on a wide range of cognitive problems testing their understanding of the physical and social world. Bonobos were more skilled at solving tasks related to theory of mind or an understanding of social causality, while chimpanzees were more skilled at tasks requiring the use of tools and an understanding of physical causality. These species differences support the role of ecological and socio-ecological pressures in shaping cognitive skills over relatively short periods of evolutionary time.


Analysis of gastrointestinal sounds in infants with pyloric stenosis before and after pyloromyotomy.
Although recent advances in computer technology enable us to analyze gastrointestinal sounds data objectively with ease, this clinical application has been investigated in only a few disorders. To investigate one potential role of this approach in pediatric practice, we recorded and analyzed gastrointestinal sounds in infants with hypertrophic pyloric stenosis (HPS), a motility-related disorder that is common in children. In 15 infants with pyloric stenosis, gastrointestinal sounds were collected with a microphone placed 3 cm below the umbilicus for 60 minutes before pyloromyotomy and at 9 to 12 hours, 20 to 24 hours, 40 to 48 hours, and 112 to 120 hours after the operation. Data were entered into a computer to sum the amplitude of sound signals as a sound index (SI; mV per minute). In 12 infants, gastric emptying was measured immediately before each sound recording, using a marker dilution-double sampling method. Before surgery, the mean SI was 4.6 +/- 1.0 mV per minute, significantly less than in healthy controls (31.7 +/- 8.4 mV per minute). The SI remained in a similar range until 12 hours after operation, after which it began increasing to reach the normal range by 48 hours after operation (30. 0 +/- 9.4 mV per minute). Gastric emptying, also low in HPS before pyloromyotomy, increased by 4 to 5 times after surgery. There was a significant positive correlation between SI and gastric emptying. The incidence of postoperative symptoms (such as vomiting) were correlated significantly with SI at 24 hours after surgery. This study found decreased gastrointestinal sounds to be among physical findings suggestive of HPS and a useful indicator of gastric emptying and bowel motility after pyloromyotomy. Computer-assisted analysis of gastrointestinal sounds might be helpful in clinical practice for pediatric patients with some gastrointestinal disorders.


Pathogenesis and sexual transmission of Spondweni and Zika viruses.
The Spondweni serogroup of viruses (Flaviviridae, Flavivirus) is comprised of Spondweni virus (SPONV) and Zika virus (ZIKV), which are mosquito-borne viruses capable of eliciting human disease. Numerous cases of ZIKV sexual transmission in humans have been documented following the emergence of the Asian genotype in the Americas. The African ZIKV genotype virus was previously implicated in the first reported case of ZIKV sexual transmission. Reports of SPONV infection in humans have been associated with non-specific febrile illness, but no association with sexual transmission has been reported. In order to assess the relative efficiency of sexual transmission of different ZIKV strains and the potential capacity of SPONV to be sexually transmitted, viral loads in the male reproductive tract and in seminal fluids were assessed in interferon α/β and -γ receptor deficient (AG129) mice. Male mice were inoculated subcutaneously with Asian genotype ZIKV strains PRVABC59 (Puerto Rico, 2015), FSS13025 (Cambodia, 2010), or P6-740 (Malaysia, 1966); African genotype ZIKV strain DakAr41524 (Senegal, 1984); or SPONV strain SAAr94 (South Africa, 1955). Infectious virus was detected in 60-72% of ejaculates collected from AG129 mice inoculated with ZIKV strains. In contrast, only 4% of ejaculates from SPONV-inoculated AG129 males were found to contain infectious virus, despite viral titers in the testes that were comparable to those of ZIKV-inoculated mice. Based on these results, future studies should be undertaken to assess the role of viral genetic determinants and host tropism that dictate the differential sexual transmission potential of ZIKV and SPONV.


Influences of community engagement and health system strengthening for cholera control in cholera reporting countries.
The 2030 Global Task Force on Cholera Control Roadmap hinges on strengthening the implementation of multistranded cholera interventions, including community engagement and health system strengthening. However, a composite picture of specific facilitators and barriers for these interventions and any overlapping factors existing between the two, is lacking. Therefore, this study aims to address this shortcoming, focusing on cholera-reporting countries, which are disproportionately affected by cholera and may be cholera endemic. A scoping methodology was chosen to allow for iterative mapping, synthesis of the available research and to pinpoint research activity for global and local cholera policy-makers and shareholders. Using the Arksey and O'Malley framework for scoping reviews, we searched PubMed, Web of Science and CINAHL. Inclusion criteria included publication in English between 1990 and 2021 and cholera as the primary document focus in an epidemic or endemic setting. Data charting was completed through narrative descriptive and thematic analysis. Forty-four documents were included, with half relating to sub-Saharan African countries, 68% (30/44) to cholera endemic settings and 21% (9/44) to insecure settings. We identified four themes of facilitators and barriers to health systems strengthening: health system cooperation and agreement with external actors; maintaining functional capacity in the face of change; good governance, focused political will and sociopolitical influences on the cholera response and insecurity and targeted destruction. Community engagement had two themes: trust building in the health system and growing social cohesion. Insecurity and the community; cooperation and agreement; and sociopolitical influences on trust building were themes of factors acting at the interface between community engagement and health system. Given the decisive role of the community-health system interface for both sustained health system strengthening and community engagement, there is a need to advocate for conflict resolution, trust building and good governance for long-term cholera prevention and control in cholera reporting countries.


Novel Iron Chelator SK4 Drives Cytotoxicity through Inhibiting Mitochondrial Metabolism in Ovarian and Triple Negative Breast Cancer Cell Lines.
Anti-cancer therapy by iron chelation has been shown to inhibit many cellular processes including DNA replication, mitochondrial metabolism and oncogenic signalling pathways (e.g., EGFR). Iron chelator SK4 represents a double pronged approach towards treating cancer. SK4 enters through LAT1, a commonly overexpressed amino acid transporter in tumours, thus targeting iron addiction and LAT1 overexpression. The aim of this study was to characterise the mode of action of SK4 through proteomics, metabolomics, lipidomics and seahorse real-time analysis in ovarian cell line SKOV3 and triple negative breast cancer cell line MDA MB 231. Pathway enrichment of proteomics data showed an overrepresentation of metabolism related pathways. Metabolic change after SK4 exposure have been confirmed in investigations of changes in basal and maximal mitochondrial respiration using seahorse real-time analysis of mitochondrial metabolism. Metabolomics also showed an increase in AMP and glucose-1-phosphate. Interestingly, our lipidomics data show a decrease in phospholipid synthesis in the SKOV3 cells which is in contrast with previous data which showed an upregulation of ceramide driven apoptosis. In summary, our data highlight impairment of energy metabolism as a mechanism of action underlying SK4 apoptosis, but also suggest a potential role of ceramide induction in the phenotypic outcome of the cell model.


Histoplasmosis presenting with solitary pulmonary nodule: two cases mimicking pulmonary metastases.
Pulmonary histoplasmosis is a granulomatous disease, whose diagnosis is not always easy, as it may simulate metastatic lesions due to similar radiographic findings. We herein report two cases of histoplasmosis with solitary pulmonary nodule in asymptomatic patients with histories of cancer surgeries, whose diagnoses were confirmed by postoperative pathological examinations. Doctors must pay attention to risk factors for immunosuppression such as the histories of chemotherapy, radiotherapy, or malignancy, which may increase chances of developing histoplasmosis. Limited surgical intervention is the treatment of choice for these localized lesions.


Malaria morbidity and pyrethroid resistance after the introduction of insecticide-treated bednets and artemisinin-based combination therapies: a longitudinal study.
Substantial reductions in malaria have been reported in several African countries after distribution of insecticide-treated bednets and the use of artemisinin-based combination therapies (ACTs). Our aim was to assess the effect of these policies on malaria morbidity, mosquito populations, and asymptomatic infections in a west African rural population. We did a longitudinal study of inhabitants of Dielmo village, Senegal, between January, 2007, and December, 2010. We monitored the inhabitants for fever during this period and we treated malaria attacks with artesunate plus amodiaquine. In July, 2008, we offered longlasting insecticide (deltamethrin)-treated nets (LLINs) to all villagers. We did monthly night collections of mosquitoes during the whole study period, and we assessed asymptomatic carriage from cross-sectional surveys. Our statistical analyses were by negative binomial regression, logistic regression, and binomial or Fisher exact test. There were 464 clinical malaria attacks attributable to Plasmodium falciparum during 17,858 person-months of follow-up. The incidence density of malaria attacks averaged 5·45 (95% CI 4·90-6·05) per 100 person-months between January, 2007, and July, 2008, before the distribution of LLINs. Incidence density decreased to 0·41 (0·29-0·55) between August, 2008, and August, 2010, but increased back to 4·57 (3·54-5·82) between September and December, 2010--ie, 27-30 months after the distribution of LLINs. The rebound of malaria attacks were highest in adults and children aged 10 years or older: 45 (63%) of 71 malaria attacks recorded in 2010 compared with 126 (33%) of 384 in 2007 and 2008 (p<0·0001). 37% of Anopheles gambiae mosquitoes were resistant to deltamethrin in 2010, and the prevalence of the Leu1014Phe kdr resistance mutation increased from 8% in 2007 to 48% in 2010 (p=0·0009). Increasing pyrethroid resistance of A gambiae and increasing susceptibility of older children and adults, probably due to decreasing immunity, caused the rebound and age shift of malaria morbidity. Strategies to address the problem of insecticide resistance and to mitigate its effects must be urgently defined and implemented. Institut de Recherche pour le Développement and the Pasteur Institute of Dakar.


Photofabricated gelatin-based nerve conduits: nerve tissue regeneration potentials.
There is a strong demand for development of nerve guide conduit with prompt nerve regeneration potential for injury-induced nerve defect. Prior to study on nerve tissue engineering using Schwann cells or nerve stem cells, the effectiveness of photofabricated scaffolds based on photocurable gelatin was examined. This study describes the evaluation of in vivo nerve tissue regeneration potentials of three custom-designed and -fabricated prostheses (inner diameter, 1.2 mm; outer diameter, 2.4 mm; wall thickness, 0.60 mm; and length, 15 mm) made of photocured gelatin: a plain photocured gelatin tube (model I), a photocured gelatin tube packed with bioactive substances (laminin, fibronectin, and nerve growth factor) coimmobilized in a photocured gelatin rod (model II), and a photocured gelatin tube packed with bioactive substances coimmobilized in multifilament fibers (model III). These prostheses were implanted between the proximal and distal stumps 10 mm of the dissected right sciatic nerve of 70 adult male Lewis rats for up to 1 year. The highest regenerative potentials were found using the model III prosthesis, followed by the model II prosthesis. Markedly retarded neural regeneration was observed using the model I prosthesis. These were evaluated from the viewpoints of functional recovery, electrophysiological responses, and tissue morphological regeneration. The significance of the synergistic cooperative functions of multifilaments, which serve as a platform that provides contact guidance to direct longitudinal cell movement and tissue ingrowth and as a cell adhesive matrix with high surface area, and immobilized bioactive substances, which enhance nerve regeneration via biological stimulation, is discussed.


Fire effects on tree physiology.
Heat injuries sustained in a fire can initiate a cascade of complex mechanisms that affect the physiology of trees after fires. Uncovering the exact physiological mechanisms and relating specific injuries to whole-plant and ecosystem functioning is the focus of intense current research. Recent studies have made critical steps forward in our understanding of tree physiological processes after fires, and have suggested mechanisms by which fire injuries may interact with disturbances such as drought, insects and pathogens. We outline a conceptual framework that unifies the involved processes, their interconnections, and possible feedbacks, and contextualizes these responses with existing hypotheses for disturbance effects on plants and ecosystems. By focusing on carbon and water as currencies of plant functioning, we demonstrate fire-induced cambium/phloem necrosis and xylem damage to be main disturbance effects. The resulting carbon starvation and hydraulic dysfunction are linked with drought and insect impacts. Evaluating the precise process relationships will be crucial for fully understanding how fires can affect tree functionality, and will help improve fire risk assessment and mortality model predictions. Especially considering future climate-driven increases in fire frequency and intensity, knowledge of the physiological tree responses is important to better estimate postfire ecosystem dynamics and interactions with climate disturbances.


[Criteria of diagnostics of pancreatitis at children's age according to ultrasound research].
In the article new criteria of diagnostics of chronic and reactive pancreatitis due to sonography data are described. Among symptoms of reactive pancreatitis are as follows: presence of pancreatic edema, appearance of hyper echogenic lineal admixtures (visualization of connective tissues jumpers). Among criteria of reactive pancreatitis due to ultrasonography belong all as follows: local (59.7%) or diffuse hyper echogenic (18.8%) parenchyma comparatively to parenchyma of parotic gland, as well as small dots or triangle-like formations - marker of fibrosis. At the same time among signs of long-lasting pancreatitis these symptoms are also characteristic areas of hypoechogenic parenchyma which mimic areas of hyperechogenic structure of pancreas (44.0% of incidences). Widening of pancreatic duct like prominent symptom of chronic pancreatitis they noticed in 1/3 cases of reactive pancreatitis together with local edema of pancreas.


The effect of frequency of supplementing rumen-protected unsaturated fatty acids on blood serum fatty acid profiles in beef heifers and lactating cows.
The objective of this study was to determine if supplementation frequency of rumen-protected fat (RPF) influences circulating serum concentrations of fatty acids (FA), NEFA, and urea nitrogen in beef heifers and lactating cows. In Exp. 1, 12 early gestation beef heifers were supplemented 0.5 kg of corn gluten feed (CGF) daily during a 2-wk adaptation period. During the last 3 d of adaptation, blood samples were collected immediately before supplementation and then 8 and 16 h postsupplementation daily. Each heifer was then randomly assigned to 1 of 3 supplementation frequency treatments of RPF (3, 5, or 7 d/wk) for 3 wk in a 3 × 3 Latin square design with 3 periods (4 heifers per treatment per period), with each treatment receiving the same amount of RPF and CGF per wk (1.0 and 2.7 kg as fed, respectively). Blood samples were collected during the final 3 d of each supplementation period as described in the adaptation period. In Exp. 2, 18 Angus crossbred cows in early lactation were supplemented with 4.54 kg (as fed) of CGF weekly either at 3, 5, or 7 d/wk during a 2-wk adaptation period. Blood samples were collected during the last 3 d of adaptation as in Exp. 1. For the subsequent 3 wk, RPF (530, 318, and 227 g/d when supplemented) was added to the CGF supplement so that each supplementation frequency received 1.59 kg as fed/wk of RPF. Blood samples were collected during the last 3 d of supplementation as in Exp. 1. Serum FA profiles on a random subsample of 9 heifers in Exp. 1 and all animals in Exp. 2 were determined via gas chromatograph (GC), and values were analyzed using the MIXED procedure of SAS. In Exp. 1, there were no differences ( ≥ 0.53) in serum FA profile across supplementation frequencies. There was a decrease in serum 18:2, 18:1 -9 and total FA during the sampling time (time effect, < 0.02). In Exp. 2, there was treatment × time effect ( ≤ 0.001) for both 18:2 and total FA measured. The 7 d/wk frequency had a greater concentration of C18:2 and total FA at 8 h of the sampling period when compared to the other 2 frequencies. These results demonstrate that supplementation of RPF at 3, 5 or 7 d/wk resulted in no changes in serum FA profiles in growing heifers. In early lactating beef cows, there were minor time point changes in serum FA due to supplementation frequency; however, the vast majority of time points were not different, indicating no substantial changes in serum FA profiles.


Non-antimicrobial and Non-anticancer Properties of ZnO Nanoparticles Biosynthesized Using Different Plant Parts of Bixa orellana.
As traditional cancer therapy is toxic to both normal and cancer cells, there is a need for newer approaches to specifically target cancer cells. ZnO nanoparticles can be promising due their biocompatible nature. However, ZnO nanoparticles have also shown cytotoxicity against mammalian cells in some cases, because of which there is a need for newer synthesis approaches for biocompatible ZnO nanoparticles to be used as carrier molecules in drug delivery applications. Here, we report the biosynthesis of ZnO nanoparticles using different plant parts (leaf, seed, and seed coat) of Bixa orellana followed by different characterizations. The UV-visible spectra of ZnO showed absorption maxima at 341 and 353 nm, 378 and 373 nm, and 327 and 337 nm, respectively, before and after calcination corresponding to the band gap energy of 3.636 and 3.513 eV, 3.280 and 3.324 eV, and 3.792 and 3.679 eV for L-ZnO, S-ZnO, and Sc-ZnO, respectively. X-ray diffraction analysis confirmed the formation of hexagonal wurtzite structures. Attenuated total reflectance infrared spectra revealed the presence of stretching vibrations of C-C, C=C, C=O, and NH3 + groups along with C-H deformation involving biomolecules from extracts responsible for reduction and stabilization of nanoparticles. Field emission scanning electron microscopy and transmission electron microscopy images showed spherical and almond-like morphologies of L-ZnO and Sc-ZnO with spherical morphologies, whereas S-ZnO showed almond-like morphologies. The presence of antibacterial activity was observed in L-ZnO against Staphylococcus aureus and Bacillus subtilis, in S-ZnO nanoparticles only against Escherichia coli, and in Sc-ZnO only against Staphylococcus aureus. Uncalcinated ZnO nanoparticles showed weak antibacterial activities, whereas calcinated ZnO nanoparticles showed a non-antibacterial nature. The antifungal activity against different fungi (Penicillium sp., Aspergillus flavus, Fusarium oxysporum, and Rhizoctonia solani) and cytotoxicity against HCT-116 cancer cells were not observed before and after calcination in all three ZnO nanoparticles. The antimicrobial nature and biocompatibility of ZnO nanoparticles were influenced by different parameters of the nanoparticles along with microorganisms and the human cells. Non-antimicrobial properties of ZnO nanoparticles can be treated as a pre-requisite for its biocompatibility due to its inert nature. Thus, biosynthesized ZnO nanoparticles showed a nontoxic nature, which can be exploited as promising alternatives in biomedical applications.


The pathogenesis of molybdenum cofactor deficiency, its delay by maternal clearance, and its expression pattern in microarray analysis.
Molybdenum cofactor (Moco)-deficiency is a lethal autosomal recessive disease, for which until now no effective therapy is available. The biochemical hallmark of this disorder is the inactivity of the Moco-dependent sulfite oxidase, which results in elevated sulfite and diminished sulfate levels throughout the organism. In humans, Moco-deficiency results in neurological damage, which is apparent in untreatable seizures and various brain dysmorphisms. We have recently described a murine model for Moco-deficiency, which reflects all enzyme and metabolite changes observed in the patients, and an efficient therapy using a biosynthetic precursor of Moco has been established in this animal model. We now analyzed these mice in detail and excluded morphological brain damage, while expression analysis with microarrays indicates a massive cell death program. This neuronal damage appears to be triggered by elevated sulfite levels and is ameliorated in affected embryos by maternal clearance.


Spatial Architecture of Nitrifying Bacteria Biofilm Immobilized on Polyurethane Foam in an Automatic Biodetector for Water Toxicity.
We describe the architecture of nitrifying bacteria biofilms immobilized on a three-dimensional (3D) polyurethane foam that permits efficient water flow through a bioreactor. The 3D spatial organization of immobilized bacterial colonies is characterized on three resolution levels with X-ray tomography, light confocal microscopy, and scanning electron microscopy (SEM). Using these techniques we demonstrate biofilm distribution in the foam and the existence of several modes of binding of bacteria to the foam. Computed X-ray tomography permits observation of the distribution of the biofilm in the whole open cellular polyurethane material volume and estimation of biofilm volume. SEM and confocal laser scanning microscopy techniques permit 3D visualization of biofilm structure. Three distinct immobilization patterns could be observed in the open cellular polyurethane material: (1) large irregular aggregates of bacterial biofilm that exist as irregular biofilm fragments, rope-like structures, or biofilm layers on the foam surface; (2) spherical (pom-pom) aggregates of bacteria localized on the external surface of biofilm; and (3) biofilm threads adherent to the surface of polyurethane foam. Finally, we demonstrate that immobilized bacteria exhibit metabolic activity and growth.


Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome (MEN1): a case-control study in a series of 77 patients versus 2509 non-MEN1 patients.
Patients affected by the multiple endocrine neoplasia type I syndrome (MEN1) display a high incidence of pituitary adenomas, though it is still unknown whether these pituitary tumors have specific pathologic features that would distinguish them from sporadic pituitary adenomas. Pituitary tissue specimens of 77 MEN1 patients from the GTE (Groupe d'étude des Tumeurs Endocrines) register were compared with unselected 2509 non-MEN1 sporadic pituitary tumors and also to a control subgroup of 296 cases, where 1 MEN1 tumor was matched with 4 sporadic tumors of the same hormonal immunoprofile. Sex, age, size, and invasiveness of tumors, and menin gene mutations were documented. Histologic analysis took into account 33 items, including immunocytochemical data, the proliferative marker Ki-67, and an examination of the juxtatumoral pituitary. MEN1 tumors were significantly larger and more often invasive by histology. MEN1 patients with large pituitary tumors (grade IV) were younger than non-MEN1 patients. MEN1 tumors had no other characteristic histologic features and no predominance of any one hormone producing subtype. However, plurihormonal adenomas versus monohormonal and nonimmunoreactive adenomas were more frequent in MEN1 tumors (39%) than in the control non-MEN1 group (P = 0.001). Especially, the growth hormone and prolactin plurihormonality with unusual association with follicle-stimulating hormone, luteinizing hormone, or adrenocorticotropic hormone was more frequent in MEN1 tumors. In addition, multiple adenomas were significantly more frequent (4% vs. 0.1%; P < 0.0001), especially prolactin-adrenocorticotropic hormone. Somatotroph hyperplasia, with or without a microadenoma was found in only 3 MEN1 patients, with growth hormone-releasing hormone hypersecretion by a pancreatic tumor in 2 of them. All types of mutation were observed, including frameshifts, nonsenses, missenses, and 1 case of germline MEN1 encompassing large deletion, strongly suggesting the absence of any phenotype-genotype correlation.


Appendicitis during Pregnancy: The Clinical Experience of a Secondary Hospital.
Appendicitis is the most common condition leading to an intra-abdominal operation for a non-obstetric problem in pregnancy. The aim of this study was to examine our experience and to analyze the clinical characteristics and the pregnancy outcomes for appendicitis during pregnancy that was reported in Korea. We reported 25 cases of appendicitis during pregnancy that were treated at Good Moonhwa Hospital from January 2004 to March 2010. We also analyzed appendicitis during pregnancy reported in Korea between 1970 and 2008 by a review of journals. The incidence of acute appendicitis during pregnancy was one per 568 deliveries. The mean age was 27.92 years old, the gestational stage at the onset of symptoms was the first trimester in 10 patients (40%), the second trimester in 14 patients (56%), and the third trimester in 1 patient (4%). Among the 25 cases, 21 were treated with an open appendectomy and 4 with laparoscopic appendectomies. The postoperative complications were 2 wound infections and 1 spontaneous abortion. Our experience demonstrated that appendectomies on pregnant patients can be successfully performed at secondary hospitals.


Short communication controlling LC-SPE-NMR systems.
There are several stages of the LC-SPE-NMR process that should be monitored closely to ensure an efficient isolation and concentration of the target analyte, for instance analyte break-through and compound transfer from the LC-SPE to the NMR probe. In this study, analyte break-through monitoring was performed with a UV detector and a mass spectrometer placed after the SPE unit. Easy break-through was a problem when attempting multiple trapping of various compounds using C18 SPE cartridges with the original commercial system. However, on lowering the flow rate over the SPE system and using SPE cartridges packed with porous carbon, the number of trappings possible increased five-fold. To increase control over the on-line SPE-NMR transfer, a gradient pump-UV system was used to elute compounds trapped on an SPE to an NMR probe. The analyte band was placed in the active volume of the probe by a stop-flow mechanism. The modified LC-SPE system was also coupled with off-line NMR analysis for determination of a degradation product of the insecticide monuron, present in the low ppm range.


Screening of ROS1 rearrangements in lung adenocarcinoma by immunohistochemistry and comparison with ALK rearrangements.
ROS1 rearrangement is a predictive biomarker for response to the tyrosine kinase inhibitor, crizotinib. We investigated the usefulness of ROS1 immunohistochemistry (IHC) for the detection of patients who harbor ROS1 rearrangements in two separate cohorts. We also compared ROS1 IHC with ALK IHC in terms of diagnostic performance to predict each gene rearrangement. In a retrospective cohort, IHC was performed in 219 cases of lung adenocarcinoma with already known genetic alterations. In a prospective cohort, we performed IHC for 111 consecutive cases of lung adenocarcinoma and confirmed the results by subsequent FISH. In the retrospective cohort, all 8 ROS1-rearranged tumors were immunoreactive, and 14 of 211 ROS1-wild cases were immunoreactive (sensitivity 100% and specificity 93.4%). In the prospective cohort, all IHC-negative cases were FISH-negative, and 5 of 34 ROS1 immunoreactive cases were ROS1-rearranged (sensitivity 100% and specificity 72.6%). In ROS1-wild tumors, ROS1 protein was more expressed in the tumors of ever-smokers than in those of never-smokers (p = 0.003). ALK IHC showed 100% sensitivity and 98.1 to 100% specificity in both patient cohorts. In conclusion, ROS1 IHC is highly sensitive, but less specific compared with ALK IHC for detection of the corresponding rearrangement. ROS1 IHC-reactive tumors, especially when the tumor is stained with moderate to strong intensity or a diffuse pattern, are recommended to undergo FISH to confirm the gene rearrangement.


[Gastrointestinal hemorrhage needing blood transfusion as the first manifestation of small bowel carcinoid tumor].
Carcinoid tumors arise from enterochromaffin or enterochromaffin-like cells that are present in the gastrointestinal tract, ovaries, and lungs. Over 90% of carcinoids originate in the gastrointestinal tract with the most common sites in order of frequency being the appendix, terminal ileum, rectum, and the remainder of the colon. Gastroduodenal and pancreatic carcinoids are infrequent. Carcinoid syndrome is associated with small intestine carcinoids in about 40%. Common symptoms include intermittent intestinal obstruction with crampy abdominal pain and vomiting, and weight loss. Upper gastrointestinal bleeding with melaena or hematochezia is a relatively rare early symptom of patients with small intestine carcinoid tumors. We report on a 69-year-old man, treated with acenocoumarol for previous thromboembolic complications of hereditary protein S deficiency. He was admitted to hospital because of an acute episode of hematochezia followed by melaena. Endoscopic evaluation of esophagus, stomach, duodenum and colonoscopy revealed no apparent source of bleeding. Selective angiographic evaluation of mesenterial arteries showed pathologic vasculature approximately in mid jejunum. Laparotomy revealed bleeding from a small submucosal malignant carcinoid tumor in small intestine and multiple large metastases within mesenteric tissue. Segmental resection of small intestine and exstirpation of the metastatic masses was performed. Postoperative period was uneventful. Cytotoxic chemotherapy in this adjuvant setting has not been recommended. Small intestinal carcinoid tumor has to be considered as a rare cause of gastrointestinal bleeding with melaena or hematochezia. Nevertheless, bleeding is a relatively rare early symptom of patients with small intestine carcinoid tumor.


SR compartment calcium and cell apoptosis in SERCA overexpression.
The relationship between SR Ca2+ ATPase (SERCA) activities, cell calcium level, SR calcium store and cell cycle events is not clearly understood. We studied SERCA overexpression in Cos cells using an adenovirus vector. Twofold increases in SERCA mRNA and in protein were correlated with a 2.3-fold and a 1.6-fold paralleled increase in SR calcium pump activity (R = 0.97 and R = 0.99 respectively). Dose-related apoptotic cell death was associated with SERCA overexpression (R = 0.92). When serum was reduced to 4%, cell apoptosis further increased from 20.7 +/- 4.8% to 47.5 +/- 12.9% (M+/-SD; P<0.05; n=3). Flow cytometry identified cell cycle arrest at the G2/M phase. The interleukin-1 converting enzyme (ICE) inhibitor z-VAD-fmk reduced apoptosis for low-, medium- and high-expressing constructs, whereas the CPP-32 inhibitor z-DEVD-fmk had no effect. Flow cytometry using Fluo-3 and Fura-Red revealed a 1.5-fold higher basal calcium and a 10-fold SR calcium overload. ICE inhibitor z-VAD-fmk did not alter calcium loading. An epitope-tagged SERCA mutant, which has no intrinsic Ca2+-pump activities, had a much smaller effect on the SR calcium. These findings suggest that SERCA2A overexpression has an intrinsic role in altering cell-cycle progression, augmenting cellular and SR calcium loading, and precipitating ICE protease-mediated apoptosis; this represents as a novel model for primary SR calcium overload and associated cell apoptosis.


Unpacking the burden: understanding the relationships between chronic pain and comorbidity in the general population.
We investigated the association of chronic pain with physical and mental comorbidity in the New Zealand population by measuring chronic pain status separate from comorbid conditions. Models of allostatic load provided a conceptual basis for considering multi-morbidity as accumulated comorbid load and for using both discrete conditions and cumulative measures in analyses. The nationally representative cross-sectional survey data included self-reported doctor-diagnosed chronic physical and mental health conditions, Kessler 10-item scale scores, an independent measure of chronic pain, and sociodemographic characteristics. The population prevalence of chronic pain is 16.9%, and a quarter (26%) of the population report 2 or more comorbid physical conditions statistically associated with chronic pain (unadjusted P<0.01). Results indicate that accumulated comorbid load is independently associated with chronic pain. Six physical conditions independently associated with chronic pain (adjusted odds range from 1.4 to 3.9) increase the risk of chronic pain in an additive manner, and residual accumulated load further increases risk for 2 or more conditions (adjusted odds 1.6). Anxiety/depression interacts synergistically with arthritis and neck/back disorders to increase the odds of reporting chronic pain beyond an additive model. This synergistic effect is not apparent for other conditions or for additional comorbid load. Results imply that measurement of chronic pain independent of comorbid conditions and adjustment for comorbid conditions is important for more accurate prevalence estimates and understanding relationships between conditions. Future epidemiological research might usefully incorporate independent measurement of chronic pain alongside adjustment for specific physical and mental health conditions as well as accumulated comorbid load.


Impact of hepatitis C viral replication on CD4+ T-lymphocyte progression in HIV-HCV coinfection before and after antiretroviral therapy.
HIV is known to have a negative impact on the progression of hepatitis C virus (HCV) infection, whereas the reverse remains unclear. We examined the impact of spontaneous clearance of HCV on CD4(+) T-lymphocyte count progression before and after initiation of antiretroviral therapy (ART) in HIV-HCV coinfected adults. Data were analysed from participants in a Canadian, multisite prospective cohort of HIV-infected adults with serologic evidence of HCV infection. The rate of CD4(+) T-lymphocyte change was determined using multivariate mixed linear regression comparing chronically HCV RNA+ with spontaneous clearers (persistently HCV RNA- without HCV therapy). Baseline characteristics of the 271 participants analysed did not differ between individuals whose HCV RNA cleared (n = 35) and those whose HCV RNA persisted (n = 236) except with respect to markers of liver disease. HCV RNA+ individuals had on average seven-times slower recovery of CD4(+) T-cells on chronic ART compared with HCV RNA-: (adjusted change in absolute CD4 cell T-lymphocyte count per year: 4 (95% confidence interval, -0.6 to 8) cells/microl vs. 26 (95% confidence interval, 12 to 41) cells/microl; P < 0.001. Analyses restricted to individuals initiating ART showed similar results. There was also a trend to greater CD4 decline prior to ART initiation among those HCV RNA+, although this did not reach statistical significance. We found that CD4 cell progression is negatively affected by the presence of ongoing HCV replication in coinfected individuals initiating ART which persisted throughout stable ART suggesting active HCV infection affects immune restoration even after years of ART exposure.


Reducing children's injection pain: lidocaine patches versus topical benzocaine gel.
The purpose of this study was to compare the effectiveness of lidocaine patches and topical anesthetic gel in reducing injection pain in children. Thirty-two children received bilateral greater palatine injections of 0.2 cc of 2% lidocaine with 1:100,000 epinephrine at the same visit. Injections followed a 15 minute application of DentiPatch (20% lidocaine) or a 1 minute application of topical anesthetic gel (Topex, 20% benzocaine). Each child completed a Faces Pain Scale and Visual Analog Scale after each injection and was asked which injection hurt more. Injections were videotaped and two independent evaluators, using the Sounds, Eyes, and Motor Scale, rated observed pain-related behavior. Inter-rater reliability was established at 96%. A significant difference was shown in observed pain-sounds favoring use of the DentiPatch (P < .003, Wilcoxon Sign Rank Test). Using Wilcoxon Sign Rank Test and paired t-tests, no significant differences were shown in either reported pain or observed pain-motor. A statistically significant decrease in observed verbal indicators of injection pain was found when the DentiPatch was used 20%: compared to a 1 minute application of topical anesthetic gel. However, no significant difference was found between the two study groups in either reported pain or observed pain-motor responses.


Safety of non-antiarrhythmic drugs that prolong the QT interval or induce torsade de pointes: an overview.
The long and growing list of non-antiarrhythmic drugs associated with prolongation of the QT interval of the electrocardiogram has generated concern not only for regulatory interventions leading to drug withdrawal, but also for the unjustified view that QT prolongation is usually an intrinsic effect of a whole therapeutic class [e.g. histamine H(1) receptor antagonists (antihistamines)], whereas, in many cases, it is displayed only by some compounds within a given class of non-antiarrhythmic drugs because of an effect on cardiac repolarisation. We provide an overview of the different classes of non-antiarrhythmic drugs reported to prolong the QT interval (e.g. antihistamines, antipsychotics, antidepressants and macrolides) and discusses the clinical relevance of the QT prolonging effect. Drug-induced torsade de pointes are sometimes considered idiosyncratic, totally unpredictable adverse drug reactions, whereas a number of risk factors for their occurrence is now recognised. Widespread knowledge of these risk factors and implementation of a comprehensive list of QT prolonging drugs becomes an important issue. Risk factors include congenital long QT syndrome, clinically significant bradycardia or heart disease, electrolyte imbalance (especially hypokalaemia, hypomagnesaemia, hypocalcaemia), impaired hepatic/renal function, concomitant treatment with other drugs with known potential for pharmacokinetic/pharmacodynamic interactions (e.g. azole antifungals, macrolide antibacterials and class I or III antiarrhythmic agents). This review provides insight into the strategies that should be followed during a drug development program when a drug is suspected to affect the QT interval. The factors limiting the predictive value of preclinical and clinical studies are also outlined. The sensitivity of preclinical tests (i.e. their ability to label as positive those drugs with a real risk of inducing QT pronglation in humans) is sufficiently good, but their specificity (i.e. their ability to label as negative those drugs carrying no risk) is not well established. Verapamil is a notable example of a false positive: it blocks human ether-a-go-go-related (HERG) K(+) channels, but is reported to have little potential to trigger torsade de pointes. Although inhibition of HERG K(+) channels has been proposed as a primary test for screening purposes, it is important to remember that several ion currents are involved in the generation of the cardiac potential and that metabolites must be specifically tested in this in vitro test. At the present state of knowledge, no preclinical model has an absolute predictive value or can be considered as a gold standard. Therefore, the use of several models facilitates decision making and is recommended by most experts in the field.


Functional outcomes for older adults with cognitive impairment in a comprehensive outpatient rehabilitation facility.
The purpose of the study was to examine functional outcomes of a nurse-managed, community-based Comprehensive Outpatient Rehabilitation Facility (CORF) for frail older adults and to compare the outcomes between two groups: older adults with cognitive impairment and those with intact cognition. A retrospective cohort design using healthcare record abstraction was used for the study. Two hundred and one older adults who were admitted to the CORF from the end of 1997 to early 1999 were included in the study. Data were abstracted from healthcare records, including clinician-generated Mini-Mental State Examination, Geriatric Depression Scale, and Functional Independence Measure scores from the healthcare records and investigator-constructed measures of functional gain, rehabilitation efficiency, days of service, and discharge location. Multivariate regression analyses were performed to compare rehabilitation outcomes between the two groups. Regardless of cognitive status, all subjects improved significantly in their levels of functional dependence through participating in this outpatient rehabilitation program (P<.001). Subjects with cognitive impairment exhibited more functional dependence at baseline and discharge than did their cognitively intact counterparts. Nevertheless, there was no difference between the two groups in functional gain (P=.63), rehabilitation efficiency (P=.66), days of service (P=.83), or discharge location (P=.69). Therefore, despite their greater degree of functional dependence on admission, older adults with cognitive impairment benefited from this CORF without requiring more days of service and should thus be referred for rehabilitation services.


Transcription factor GATA-4 is activated by phosphorylation of serine 261 via the cAMP/protein kinase a signaling pathway in gonadal cells.
Gonadal gene expression is regulated by pituitary hormones acting through the cAMP/protein kinase A (PKA) signal transduction pathway. The downstream molecular effectors of these signals, however, have yet to be fully understood. We have recently shown that cAMP stimulation of gonadal cells leads to phosphorylation of the transcription factor GATA-4, a key regulator of gonadal gene expression, thus suggesting that this factor might be a novel target for the cAMP/PKA signaling pathway. We now show that the rapid phosphorylation of GATA-4 induced by cAMP in vivo can be blocked by a PKA-specific inhibitor but not by mitogen-activated protein kinase inhibitors, indicating that GATA-4 is predominantly phosphorylated by PKA in response to cAMP in gonadal cells. In addition, using in vitro kinase assays, we show that PKA phosphorylation of GATA-4 occurs predominantly on an evolutionarily conserved serine residue located at position 261. Phosphorylation of GATA-4 Ser261 by PKA enhances its transcriptional activity on different gonadal promoters, an effect that was markedly reduced with a S261A mutant. Moreover, the S261A mutant blunted cAMP-induced promoter activity in gonadal cells. Finally, PKA-dependent phosphorylation of GATA-4 also led to enhanced recruitment of the CREB-binding protein coactivator. This recruitment and transcriptional cooperation were dramatically impaired with the S261A mutant. Thus, our results identify GATA-4 as a novel downstream effector of cAMP/PKA signaling in gonadal cells, where phosphorylation of Ser261 and recruitment of CREB-binding protein likely represent a key mechanism for conveying the cAMP responsiveness of gonadal genes that lack classical cAMP regulatory elements.


An aberrant thymus in CCR5-/- mice is coupled with an enhanced adaptive immune response in fungal infection.
CCR5 is a potent mediator of regulatory T cell (Treg) chemotaxis. In murine histoplasmosis, mice lacking CCR5 or endogenous CCL4 have a reduced number of Tregs in the lungs, which results in accelerated resolution of infection. In this study, we demonstrate that CCR5 controls the outcome of Histoplasma capsulatum infection by dictating thymic and lymph node egress of Tregs. Mice lacking CCR5 or treated with a mAb to CCL4 had more Tregs in the thymus prior to and during infection. Thymic accumulation was associated with diminished transcription of the sphingosine 1-phosphate 1 receptor and Krüppel-like factor 2, both of which regulate thymic and lymph node emigration of T cells. The significance of CCR5 in Treg egress was demonstrated by generating mixed bone marrow chimeras. Chimeric mice had an increased proportion of CCR5(-/-) Tregs in the thymus and lymph nodes and a decreased proportion of Tregs in the lungs prior to and during H. capsulatum infection. Hence, CCR5 signaling regulates pathogen persistence in murine histoplasmosis by regulating Tregs exiting from the thymus and lymph nodes and, consequently, their subsequent homing in the periphery.


Effect of selenium deficiency on the development of central nervous system lesions in murine listeriosis.
The effect of selenium (Se) deficiency, produced by feeding a Se-deficient diet, on the development of central nervous system (CNS) lesions was studied in mice infected with Listeria monocytogenes, administered in drinking water for 1 or 7 days in a daily dose of 10(9)organisms, or for 7 days in a daily dose of 10(7). Se-deficient mice differed from Se-normal controls in developing CNS lesions significantly more frequently. Moreover, regardless of Se status, mice receiving repeated doses of 10(9)organisms differed from those receiving a single 10(9)dose in showing CNS lesions at least twice as often. The majority of animals with CNS lesions showed an inflammatory pattern of rhombencephalitis (17/24), while only two of 24 showed choroiditis-ventriculitis-meningitis; five of 24 animals showed both inflammatory patterns. Listeria monocytogenes antigen was identified within the areas of inflammation by an immunoperoxidase technique. Neuritis of the trigeminal nerve was present in eight animals. The relative lack of pathological changes in the liver and spleen validates this murine model for the study of CNS listeriosis.


Effect of cessation and resumption of static hamstring muscle stretching on joint range of motion.
Single group repeated measures. To determine the effects of cessation and resumption of a hamstring muscle stretching protocol on knee range of motion (ROM). It is generally accepted that stretching exercises result in an increase in ROM. The ability to maintain ROM once stretching has ceased and the ability to regain ROM after resumption of the stretching exercise is not well-known. Evaluated the effect of 6 weeks of static hamstring stretching, 4 weeks with cessation from stretching, and 6 weeks with resumption of stretching on knee ROM in 18 inactive college students (12 men, 6 women, mean age 21.0 years). The hamstring stretching consisted of 2 30-second stretches per day, 5 days per week. Knee ROM was measured before and after each of the above phases with an active knee extension test. Mean knee ROM increased after the initial stretching period (143+/-11 to 152+/-9 degrees), decreased to baseline following the cessation period (145+/-8 degrees) and again increased following the resumption of stretching but was not different from the initial gains (154+/-10 degrees). Unlike the stretch limb, the control limb ROM did not change over the 4 measurement times. There was no retention of knee ROM 4 weeks following a 6-week stretching protocol and a subsequent stretching period did not enhance the gain of knee ROM over the initial stretching period.


A simple machine learning approach for preoperative diagnosis of esophageal burns after caustic substance ingestion in children.
The unresolved debate about the management of corrosive ingestion is a major problem both for the patients and healthcare systems. This study aims to demonstrate the presence and the severity of the esophageal burn after caustic substance ingestion can be predicted with complete blood count parameters. A multicenter, national, retrospective cohort study was performed on all caustic substance cases between 2000 and 2018. The classification learner toolbox of MATLAB version R2021a was used for the classification problem. Machine learning algorithms were used to forecast caustic burn. Among 1839 patients, 142 patients (7.7%) had burns. The type of the caustic and the PDW (platelet distribution width) values were the most important predictors. In the acid group, the AUC (area under curve) value was 84% while it was 70% in the alkaline group. The external validation had 85.17% accuracy in the acidic group and 91.66% in the alkaline group. Artificial intelligence systems have a high potential to be used in the prediction of caustic burns in pediatric age groups.


Aluminum rapidly depolymerizes cortical microtubules and depolarizes the plasma membrane: evidence that these responses are mediated by a glutamate receptor.
Efforts to understand how plants respond to aluminum have focused on describing the symptoms of toxicity and elucidating mechanisms of tolerance; however, little is known about the signal transduction steps that initiate the plant's response. Here, we image cortical microtubules and quantify plasma-membrane potential in living, root cells of intact Arabidopsis seedlings. We show that aluminum depolymerizes microtubules and depolarizes the membrane, and that these responses are prevented by calcium channel blockade. Calcium influx might involve glutamate receptors, which in animals are ligand-gated cation channels and are present in the Arabidopsis genome. We show that glutamate depolymerizes microtubules and depolarizes the plasma membrane. These responses, and also the inhibition of root elongation, occur within the first few min of treatment, but are evoked more rapidly by glutamate than by aluminum. Microtubule depolymerization and membrane depolarization, induced by either glutamate or aluminum, are blocked by a specific antagonist of ionotropic glutamate receptors, 2-amino-5-phosphonopentanoate; whereas an antagonist of an aluminum-gated anion channel blocks the two responses to aluminum but not to glutamate. For growth, microtubule integrity, and membrane potential, responses to combined glutamate and aluminum were not greater than to glutamate alone. We propose that signaling in response to aluminum is initiated by efflux of a glutamate-like ligand through an anion channel and the binding of this ligand to a glutamate receptor.


Computational fluid dynamic analysis of the initiation of cerebral aneurysms.
Relationships between aneurysm initiation and hemodynamic factors remain unclear since de novo aneurysms are rarely observed. Most previous computational fluid dynamics (CFD) studies have used artificially reproduced vessel geometries before aneurysm initiation for analysis. In this study, the authors investigated the hemodynamic factors related to aneurysm initiation by using angiographic images in patients with cerebral aneurysms taken before and after an aneurysm formation. The authors identified 10 cases of de novo aneurysms in patients who underwent follow-up examinations for existing cerebral aneurysms located at a different vessel. The authors then reconstructed the vessel geometry from the images that were taken before aneurysm initiation. In addition, 34 arterial locations without aneurysms were selected as control cases. Hemodynamic parameters acting on the arterial walls were calculated by CFD analysis. In all de novo cases, the aneurysmal initiation area corresponded to the highest wall shear stress divergence (WSSD point), which indicated that there was a strong tensile force on the arterial wall at the initiation area. The other previously reported parameters did not show such correlations. Additionally, the pressure loss coefficient (PLc) was statistically significantly higher in the de novo cases (p < 0.01). The blood flow impact on the bifurcation apex, or the secondary flow accompanied by vortices, resulted in high tensile forces and high total pressure loss acting on the vessel wall. Aneurysm initiation may be more likely in an area where both tensile forces acting on the vessel wall and total pressure loss are large.


Downregulation of renal CYP-derived eicosanoid synthesis in rats with diet-induced hypertension.
The incidence of essential hypertension increases with obesity; however, the mechanisms that link obesity with hypertension are unclear. Renal cytochrome P450 (CYP)-derived eicosanoids--hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DHETs)--have been shown to play an important role in the regulation of renal function, vascular tone, and blood pressure. The objective of this study was to examine CYP-derived eicosanoid synthesis in the different renal zones (cortex, medulla, and papilla) of rats fed a high fat diet (HF). Male Sprague-Dawley rats were fed a HF diet or regular rat chow for 10 weeks. After 10 weeks, HF rats showed significantly higher systolic blood pressure, body weight, and fat:body weight ratio. The renal omega-hydroxylase activity was decreased by 46% in cortex, 43% in medulla, and 46% in papilla of HF rats. The renal epoxygenase activity was decreased by 46% in cortex, 31% in medulla, and 56% in papilla of HF rats. Interestingly, the changes in the rate of 20-HETE and EET formation in different renal zones were consistent with the levels of expression of CYP4A and CYP2C23 proteins, respectively. Furthermore, there were no significant changes in the synthesis of these metabolites in the renal microvessels. These results demonstrate that HF diet causes the downregulation of CYP4A and CYP2C23 in renal tubules, and these proteins are responsible for renal 20-HETE and EET formation. The reduction in the synthesis of these eicosanoids may play an important role in the regulation of renal function and blood pressure in obesity-induced hypertension.


Fullerenols and glucosamine fullerenes reduce infarct volume and cerebral inflammation after ischemic stroke in normotensive and hypertensive rats.
Cerebral inflammation plays a crucial role in the pathophysiology of ischemic stroke and is involved in all stages of the ischemic cascade. Fullerene derivatives, such as fullerenol (OH-F) are radical scavengers acting as neuroprotective agents while glucosamine (GlcN) attenuates cerebral inflammation after stroke. We created novel glucosamine-fullerene conjugates (GlcN-F) to combine their protective effects and compared them to OH-F regarding stroke-induced cerebral inflammation and cellular damage. Fullerene derivatives or vehicle was administered intravenously in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) immediately after transient middle cerebral artery occlusion (tMCAO). Infarct size was determined at day 5 and neurological outcome at days 1 and 5 after tMCAO. CD68- and NeuN-staining were performed to determine immunoreactivity and neuronal survival respectively. Cytokine and toll like receptor 4 (TLR-4) expression was assessed using quantitative real-time PCR. Magnetic resonance imaging revealed a significant reduction of infarct volume in both, WKY and SHR that were treated with fullerene derivatives. Treated rats showed an amelioration of neurological symptoms as both OH-F and GlcN-F prevented neuronal loss in the perilesional area. Cerebral immunoreactivity was reduced in treated WKY and SHR. Expression of IL-1β and TLR-4 was attenuated in OH-F-treated WKY rats. In conclusion, OH-F and GlcN-F lead to a reduction of cellular damage and inflammation after stroke, rendering these compounds attractive therapeutics for stroke.


Structure and mineralization of the spearing mantis shrimp (Stomatopoda; Lysiosquillina maculata) body and spike cuticles.
Stomatopoda is a crustacean order including sophisticated predators called spearing and smashing mantis shrimps that are separated from the well-studied Eumalacotraca since the Devonian. The spearing mantis shrimp has developed a spiky dactyl capable of impaling fishes or crustaceans in a fraction of second. In this high velocity hunting technique, the spikes undergo an intense mechanical constraint to which their exoskeleton (or cuticle) has to be adapted. To better understand the spike cuticle internal architecture and composition, electron microscopy, X-ray microanalysis and Raman spectroscopy were used on the spikes of 7 individuals (collected in French Polynesia and Indonesia), but also on parts of the body cuticle that have less mechanical stress to bear. In the body cuticle, several specificities linked to the group were found, allowing to determine the basic structure from which the spike cuticle has evolved. Results also highlighted that the body cuticle of mantis shrimps could be a model close to the ancestral arthropod cuticle by the aspect of its biological layers (epi- and procuticle including exo- and endocuticle) as well as by the Ca-carbonate/phosphate mineral content of these layers. In contrast, the spike cuticle exhibits a deeply modified organization in four functional regions overprinted on the biological layers. Each of them has specific fibre arrangement or mineral content (fluorapatite, ACP or phosphate-rich Ca-carbonate) and is thought to assume specific mechanical roles, conferring appropriate properties on the entire spike. These results agree with an evolution of smashing mantis shrimps from primitive stabbing/spearing shrimps, and thus also allowed a better understanding of the structural modifications described in previous studies on the dactyl club of smashing mantis shrimps.


Review: Genetic and protein variants of milk caseins in goats.
The milk casein genes in goats, are highly polymorphic genes with numerous synonymous and non-synonymous mutations. So far, 20 protein variants have been reported in goats for alpha-S1-casein, eight for beta-casein, 14 for alpha-S2-casein, and 24 for kappa-casein. This review provides a comprehensive overview on identified milk casein protein variants in goat and non-coding DNA sequence variants with some affecting the expression of the casein genes. The high frequency of some casein protein variants in different goat breeds and geographical regions might reflect specific breeding goals with respect to milk processing characteristics, properties for human nutrition and health, or adaptation to the environment. Because protein names, alongside the discovery of protein variants, go through a historical process, we linked old protein names with new ones that reveal more genetic variability. The haplotypes across the cluster of the four genetically linked casein genes are recommended as a valuable genetic tool for discrimination between breeds, managing genetic diversity within and between goat populations, and breeding strategies. The enormous variation in the casein proteins and genes is crucial for producing milk and dairy products with different properties for human health and nutrition, and for genetic improvement depending on local breeding goals.


Multiple Endocrine Neoplasia Type 2B Unmasked by 18 F-FDG PET/CT and 131 I-MIBG SPECT/CT.
F-FDG PET/CT was performed to detect an occult malignancy in a 26-year-old woman with complicated medical history which included paroxysmal hypertension and significantly elevated tumor marker. The images revealed lesions in the thyroid, lymph nodes, and bilateral adrenal glands. Further I-MIBG SPECT/CT revealed intense activity in the lesion in the left adrenal gland, which was consistent with pheochromocytoma. The pathology examination after subsequent neck biopsy demonstrated medullary thyroid carcinoma. A diagnosis of multiple endocrine neoplasia type 2B was eventually made.