Loading rate patterns in scoliotic children during gait: the impact of the schoolbag carriage and the importance of its position.
Concerns have been raised regarding the effects of schoolbag carriage on adolescent schoolchildren and particularly those with a pre-existing spinal deformity. The purpose of this study was to determine the effect of school backpack loads in scoliotic and healthy school-age children during walking, in terms of peak vertical ground reaction forces and loading rates. We hypothesized that walking with a loaded backpack would have a greater effect on gait kinetics of scoliotic compared to healthy. Eight children with idiopathic scoliosis and eight healthy children were assessed. Kinetic data were collected using two AMTI OR6-7 force-plates, while the subjects walked freely along a 6-m walkway under three walking conditions: (1) without a schoolbag, (2) carrying a schoolbag bilaterally (over both shoulders-symmetrical load) and (3) carrying a schoolbag unilaterally (over each shoulder-asymmetrical load). Kinetic data were collected and four parameters were calculated; peak ground reaction force at the first maximum force peak (F1), time needed to reach F1 (T1), loading rate of F1 (LRF1) and total contact time (T2). We found no significant differences between the scoliotic and healthy children for any of the kinetic variables examined. In addition, the position of the bag did not seem to have any effect on loading rate. The results of this study indicate that in terms of kinetic parameters during normal gait, the schoolbag load (symmetrical or asymmetrical) does not have a different effect on children with mild adolescent idiopathic scoliosis compared to normal controls.


Bone marrow immunoscintigraphy using technetium-99m anti-granulocyte antibody in multiple myeloma.
Conventional skeletal radiography and bone scan have certain limitations in the initial evaluation of bone and bone marrow lesions in multiple myeloma (MM). In this study we investigated the value of bone marrow immunoscintigraphy (BMIS) using anti-granulocyte monoclonal antibody (AGA) for the diagnosis of bone involvement of MM, in comparison with bone scan and skeletal radiography. Whole-body BMIS using technetium-99m-labelled AGA was performed in 22 MM patients (15 male, 7 female) and the imaging findings compared with those of skeletal radiography and (99m)Tc-methylene diphosphonate bone scan. The findings of bone marrow aspiration and serum biochemical findings were also compared with BMIS findings. Abnormal findings of BMIS were defined as presence of a focal photon defect in the axial skeleton or expansion of peripheral bone marrow. A total of 124 focal lesions were detected in 19 subjects (86%) by skeletal radiography, bone scan or BMIS. BMIS detected 92 lesions (74%) in 19 subjects, whereas skeletal radiography detected 58 focal lesions (47%) in 14 and bone scan 40 lesions (32%) in 11. Fifty-one (41%) of the 124 lesions were only seen on BMIS. Spine and pelvic lesions were better visualised by BMIS, whereas skull lesions were better seen with skeletal radiography, and bone scan detected more lesions in the ribs. Marrow expansion was noted in 15 subjects (68%) on BMIS, and its grade correlated with marrow cellularity and myeloma cell percentage in bone marrow aspirates ( P=0.0055 and P=0.0541, respectively). BMIS revealed abnormal lesions in one of three stage II patients and 17 out of 19 stage III patients. The number of lesions of the thoracolumbar vertebrae on BMIS was correlated with cellularity ( P=0.0393), but not with myeloma cell percentage ( P=0.1262). These findings suggest that the results of BMIS with (99m)Tc-labelled AGA correlate with clinical stage, and thus reflect the functional status of bone marrow in MM patients. BMIS might be useful for the detection of bone involvement of MM when skeletal radiography or bone scan is inconclusive, especially for vertebral lesions.


The public debate on psychotropic medication and changes in attitudes 1990-2011.
Over the last 25 years, the appraisal of psychotropic drugs within the scientific community and their representation in the media has changed considerably. The initial optimism in the wake of the introduction of second-generation drugs has increasingly made room for a more critical evaluation of alleged advantages of these drugs. The question arises as to what extent this is reflected in similar changes in the public's attitudes towards psychiatric medication. Three representative population surveys on attitudes towards psychotropic medication were carried out in Germany in 1990 (N = 3075), 2001 (N = 2610) and 2011 (N = 1223), using the same sampling procedure, interview mode and instrument for assessing attitudes. In order to disentangle time-related effects, an age-period-cohort analysis was performed. Over the time period of 21 years, the German public's evaluation of psychotropic medication has become markedly more favourable. This change was mostly due to a period effect, i.e. concurrent influences of the social environment people are exposed to. Changes were much more pronounced in the 1990s, while over the following decade only a small, although statistically significant, increase in the favourable appraisal of medication was found. Age and birth cohort had only a minor effect on public attitudes. Our findings suggest that changes in the evaluation of the effects of psychotropic drugs within the psychiatric community and their representation in the media also affect public opinion. Given the ongoing debate about side effects and efficacy of psychiatric medication, future changes of public opinion can be expected.


Challenges in glioblastoma research: focus on the tumor microenvironment.
Glioblastoma (GBM) is the most deadly type of malignant brain tumor, despite extensive molecular analyses of GBM cells. In recent years, the tumor microenvironment (TME) has been recognized as an important player and therapeutic target in GBM. However, there is a need for a full and integrated understanding of the different cellular and molecular components involved in the GBM TME and their interactions for the development of more efficient therapies. In this review, we provide a comprehensive report of the GBM TME, which assembles the contributions of physicians and translational researchers working on brain tumor pathology and therapy in France. We propose a holistic view of the subject by delineating the specific features of the GBM TME at the cellular, molecular, and therapeutic levels.


Application of ATR-FTIR spectroscopy to the study of thermally induced changes in secondary structure of protein molecules in solid state.
FTIR spectroscopy in combination with ATR sampling technique is the most accessible analytical technique to study secondary structure of proteins both in solid and aqueous solution. Although several studies have demonstrated the applications of ATR-FTIR to study conformational changes of solid dried proteins due to dehydration, there are no reports that demonstrate the application of ATR-FTIR in the study of thermally induced changes of secondary structure of biomolecules directly on the solid state. In this study, four biomolecules of pharmaceutical interest, lysozyme, myoglobine, chymotripsin and human growth hormone (hGH), were studied on the solid state before and after different thermal treatments in order to relate changes of secondary structure to partial or total thermal denaturation processes. The results obtained provide experimental evidence that protein thermal denaturation in the solid state can be detected by displacement of carbonyl bands which correspond to conformational transformations between α-helix to β-sheet or intermolecular β-sheet; the molecules studied undergo this transformation when exposed to a temperature close to their denaturation temperature which may become irreversible depending on the extent of the heating treatment. These findings demonstrate that ATR-FTIR is an effective and time efficient technique that allows the monitoring of the protein thermal denaturation process of solid samples without further reconstitution or prior sample preparation.


Aniridia caused by a heritable chromosome 11 deletion.
A child with aniridia, multiple anomalies, severe failure to thrive, and severe psychomotor retardation is shown to have a syndrome similar to, though more severe than, other patients with overlapping deletions of the short arm of chromosome 11 (Pediatrics 64:604, 1978). Her deletion (46,XX,del [11p] [pter yields p14::p11.3 yields qter]) was derived from her mother, who has a chromosome 11 shift (46,XX,der [11] [pter yields p14::p11.3 yields q22::p14 yields p11.3::q22 yields qter]). The significance of del (11p) in the aniridia-Wilms' tumor association is discussed, and the del (11p) basis for aniridia is compared with other genetic bases for aniridia.


Comparison of plasma/serum levels of procalcitonin between infection and febrile disease flare in patients with systemic lupus erythematosus: a meta-analysis.
Currently published data regarding the potential role of procalcitonin (PCT) for the discrimination between systemic lupus erythematosus (SLE) flare and infection are contradictory. To derive a more precise evaluation, a meta-analysis was performed. Published literatures from PubMed, Embase, and the Cochrane Library were obtained. The Newcastle-Ottawa Scale was used to assess the study quality. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I 2. Eight studies including 205 SLE flare patients and 198 SLE patients with infection were finally incorporated in the meta-analysis after examining title, type, abstracts, and full text. No significant differences in plasma/serum PCT levels were found between SLE patients with flare and SLE patients with infection when all studies were pooled into the meta-analysis (pooled SMD = - 0.45, 95% CI = - 0.96 to 0.06). However, subgroup analysis showed that Asian SLE patients with infection had higher plasma/serum PCT levels when compared with SLE patients with flare (p < 0.001). Overall, there is no significant difference in plasma/serum PCT levels between SLE patients with flare and SLE patients with infection. However, plasma/serum PCT levels are significantly higher in Asian SLE patients with infection.


Functional results with advanced hypopharyngeal carcinoma treated with circular near-total pharyngolaryngectomy and jejunal free-flap repair.
Patients treated by a circular pharyngolaryngectomy for advanced hypopharyngeal carcinoma have a poor prognosis and disappointing speech restoration. Three carefully selected patients underwent a near-total laryngectomy circular pharyngectomy with jejunal free flap repair and dynamic tracheopharyngeal shunt for treatment of advanced hypopharyngeal carcinoma. They received induction chemotherapy and postoperative radiotherapy. We assessed the functional outcome. There was no major local complication. One year after the end of radiotherapy, all patients were able to eat solid diets. Two patients were able to speak immediately after the end of the treatment. After speech re-education, a high-quality tracheopharyngeal voice was restored in all three patients. Performance Status Scale for Head and Neck Cancer Patients (PSSHN) showed a mean score equal to 81/100 at 1 year. In selected patients, near-total laryngectomy circular pharyngectomy with tracheopharyngeal shunt and jejunal free-flap repair offers good voice rehabilitation without impairing swallowing function.


Prognostic relevance of stromal CD26 expression in rectal cancer after chemoradiotherapy.
CD26 is a transmembrane glycoprotein whose role in various types of malignancies, along with the potential therapeutic and diagnostic targets, has been evaluated. Preoperative chemoradiotherapy (CRT) is an effective tool for local control of rectal cancer, but the rate of disease recurrence remains high. The aim of this study was to clarify the association between CD26 expression and rectal cancer after preoperative CRT. A total of 85 patients with rectal cancer who had undergone preoperative CRT were enrolled in this study. We investigated CD26 expression in residual tumors and the surrounding stromal tissue using immunohistochemistry. Additionally, stromal CD26 gene expression was assessed by real-time quantitative polymerase chain reaction. Patients with high CD26 expression in cancer tissue more frequently had serosal invasion, vascular invasion, and a poor pathological response. High expression of CD26 in the tumor stroma was significantly correlated with histology and tumor recurrence. High CD26 expression in the stroma, but not the tumor itself, was significantly correlated with a poor prognosis. Patients expressing CD26 in the tumor stroma, based on transcriptional analysis, also had a significantly poorer prognosis than those without the expression. In multivariate analysis, lymph node metastasis and high stromal CD26 expression were identified as independent prognostic factors in patients with rectal cancer after neoadjuvant CRT. Stromal CD26 expression after preoperative CRT was significantly associated with tumor recurrence and prognosis in rectal cancer patients. Our data suggest that stromal CD26 plays an important role and is a potential therapeutic target in tumor relapse.


A primary care healthy choices intervention program for overweight and obese school-age children and their parents.
The escalating crisis of childhood overweight and obesity creates an urgent demand for evidence-based interventions that can be used by primary care providers. Therefore, the purpose of this study was to test the feasibility, acceptability, and preliminary efficacy of a theory-based Healthy Choices Intervention (HCI) Program with fifteen 9-12 year old overweight and obese children and their parents in a primary care setting. A 1-group, 7-week pre-/posttest study design was used. Outcome measures included: body mass index (BMI) percentile, physical activity and nutrition knowledge, beliefs, choices and behaviors, anxiety, depression, self-concept, and social competence. Children and parents found the HCI to be useful and informative. Positive effects of the HCI for the children included decreased BMI percentile, increased knowledge, beliefs, choices and behaviors, and self-control. Positive effects of the intervention for the parents included increased knowledge, beliefs, behaviors, and decreased anxiety. This study provides evidence to support the feasibility, acceptability, and preliminary effects of the HCI with overweight and obese school-age children and their parents within a primary care setting.


Lack of confirmatory data following Article 12 MRL reviews for 2,4-d, fenhexamid and iprovalicarb.
The European Commission mandated EFSA to issue a statement concerning confirmatory data that were not submitted by the set deadline by the applicant following Article 12 reviews under Regulation (EC) No 396/2005 for the following substances/commodity combination: 2,4-d on buckwheat and other pseudo-cereals, fenhexamid on kiwis, iprovalicarb on lettuces, escaroles/broad-leaved endives and roman rocket/rucola. EFSA prepared a statement containing a final conclusion on the completeness of the data necessary to support the existing tentative maximum residue levels (MRLs) and indications to risk managers whether or not the tentative MRLs currently established by Regulation (EC) No 396/2005 could be maintained. The statement was circulated to Member States for consultation via a written procedure before finalisation.


Continuous follow-up of surgical site infections for 30 days after colorectal surgery.
Surgical site infection (SSI) prolongs hospital stay, increases medical costs, and occasionally leads to mortality. Our goal was to clarify the differences in SSI incidence between our own data and the National Nosocomial Infections Surveillance (NNIS) data. From January 2003 to December 2006, we prospectively collected surveillance data from patients who were undergoing elective colorectal resection at the Mie University Graduate School of Medicine. Three hundred fifty-five elective colorectal resections (144 colon surgeries, 211 rectal surgeries) were included. The median patient age was 57.4 years. SSIs were identified in 60 patients. Cumulative SSI incidence was 16.9%. The average SSI onset was 8.7 days (range = 3-20 days) after operation. Nineteen patients (19/30:31.7%) developed SSI within 6 days of the operation. The incidence of SSI occurring within 6 days after the operation was 5.4%. Seventeen percent of SSIs occurred despite the use of perioperative management according to the CDC guidelines. We reported a much higher SSI incidence than that in the NNIS data. However, the SSI incidence within 6 days of surgery was similar to that of the NNIS data. The difference in SSI incidence between our data and that of the NNIS range may result from the different strict surveillance periods.


An in situ hybridization study of decorin and biglycan mRNA in mouse osteoblasts in vivo.
In situ hybridization of decorin and biglycan mRNA, principal members of small leucine-rich proteoglycan, was performed using [35S]-labeled RNA probes, in the context of the hypothesis that they show different expression patterns associated with osteoblast differentiation in mice. We adopted two ossifying sites that can clearly follow the developmental process of bone formation: ossifying tympanic ring and developing bone collar of mandibular condylar cartilage. Decorin mRNA was expressed in osteoblasts of developing tympanic ring at E14.0, as well as of developing bone collar at E15.0, but biglycan mRNA was not, indicating decorin mRNA was expressed earlier in newly differentiating osteoblasts than biglycan. With maturation of osteoblasts, biglycan mRNA became expressed and maintained its expression both in the outer region (periosteum) and in the interior region (endosteum) of bone. By contrast, decorin mRNA expression was maintained in the outer region but diminished in the interior region. These results indicate that decorin and biglycan show differential expression patterns in differentiating osteoblasts and play specific roles in bone formation.


The Never-Ending History of Octreotide in Thymic Tumors: A Vintage or A Contemporary Drug?
Thymic epithelial tumors are rare tumors usually presenting as a mass located in the anterior mediastinum and/or with symptoms deriving from associated paraneoplastic syndromes. Unresectable platinum-refractory tumors are often treated with alternative regimens, including chemotherapeutic agents as well as chemo-free regimens. The most popular unconventional therapy is represented by the somatostatin analog octreotide, which can be used alone or with prednisone. The in vivo expression of somatostatin receptors documented by imaging with indium-labeled octreotide or gallium-68 Dotapeptides, the successful use of octreotide and prednisone in a chemo-refractory patient, and, thereafter, the experiences from a case series have enforced the idea that this treatment merits consideration-as proved by its inclusion in the National Comprehensive Cancer Network guidelines. In the present review, we analyze the preclinical basis for the therapeutic use of somatostatin and prednisone in refractory thymic tumors and discuss the available studies looking at future perspectives.


Naturally occurring bacteriophages lyse a large proportion of canine and feline uropathogenic Escherichia coli isolates in vitro.
We investigated the feasibility of bacteriophage therapy to combat canine and feline Escherichia coli urinary tract infections (UTIs) by testing the in vitro lytic ability of 40 naturally occurring bacteriophages on 53 uropathogenic E. coli (UPEC). The mean number of UPEC strains lysed by an individual bacteriophage was 21/53 (40%, range 17-72%). In total, 50/53 (94%) of the UPEC strains were killed by one or more of the bacteriophages. Ten bacteriophages lysed 51% of UPEC strains individually and 92% of UPEC strains as a group. Electron microscopy and DNA sequencing of 5 'promising' bacteriophages revealed that 4 bacteriophages belonged to the lytic T4-like genus, while one displayed morphologic similarity to temperate P2-like bacteriophages. Overall, these results indicate that the majority of UPEC are susceptible to lysis by naturally occurring bacteriophages. Thus, bacteriophages show promise as therapeutic agents for treatment of canine and feline E. coli UTIs.


Case report : carbamazepine therapy in schizophrenia.
9 cases of schizophrenia meeting Spitzer's Research Diagnostic Criteria and nonrespondent to conventional treatment were treated with carbamazepine, either alone or in combination with neuroleptics and 7 cases had shown improvement.


Surgical repair of the bilateral cleft of the primary palate.
A technique to repair clefts of the primary palate is described. This technique is a combination of several surgical methods previously reported to which some modifications have been added. The advantages of this technique are compared with those associated with other surgical methods. A more natural result is obtained with this technique: The undesirable vestibular fistula is avoided and a deeper buccal sulcus is achieved. The criteria in the management of the nose and orbicular muscle is analyzed.


Anaerobic digester microbiome dynamics in response to moderate and failure-inducing shock loads of fats, oils and greases.
Accidental organic overloading (shock loading) is common during the anaerobic co-digestion of fats, oils and greases (FOG) and may lead to decreased performance or reactor failure due to the effects on the microbiome. Here, adapted and non-adapted lab-scale anaerobic digesters were exposed to FOG shocks of varying organic strengths. The microbiome was sequenced during the recovery periods employed between each shock event. Non-failure-inducing shocks resulted in enrichment of fermentative bacteria, and acetoclastic and methylotrophic methanogens. However, sub-dominant bacterial populations were largely responsible for increased biogas production observed after adaptation. Following failure events, early recovery communities were dominated by Pseudomonas and Methanosaeta while late recovery communities shifted toward sub-dominant bacterial taxa and Methanosarcina. Generally, the recovered microbiome structure diverged from that of both the initial and optimized microbiomes. Thus, while non-failure-inducing FOG shocks can be beneficial, the adaptations gained are lost after a failure event and adaptation must begin again.


Dynamic control in metabolic engineering: Theories, tools, and applications.
Metabolic engineering has allowed the production of a diverse number of valuable chemicals using microbial organisms. Many biological challenges for improving bio-production exist which limit performance and slow the commercialization of metabolically engineered systems. Dynamic metabolic engineering is a rapidly developing field that seeks to address these challenges through the design of genetically encoded metabolic control systems which allow cells to autonomously adjust their flux in response to their external and internal metabolic state. This review first discusses theoretical works which provide mechanistic insights and design choices for dynamic control systems including two-stage, continuous, and population behavior control strategies. Next, we summarize molecular mechanisms for various sensors and actuators which enable dynamic metabolic control in microbial systems. Finally, important applications of dynamic control to the production of several metabolite products are highlighted, including fatty acids, aromatics, and terpene compounds. Altogether, this review provides a comprehensive overview of the progress, advances, and prospects in the design of dynamic control systems for improved titer, rate, and yield metrics in metabolic engineering.


Selective reduction of serotonin immunoreactivity in some forebrain regions of rats induced by acute methamphetamine treatment; quantitative morphometric analysis by serotonin immunocytochemistry.
The influence of acute methamphetamine treatment on serotonin-like immunoreactive axons was studied in the rat forebrain. Animals, sacrificed 90 min after i.p. injection of methamphetamine (16 mg/kg) or saline, were processed for immunocytochemistry using serotonin antiserum. The numerical density of immunoreactive boutons of terminals and varicosities was quantitatively analyzed by a computer-assisted image analyzer. Compared with the control, administration of methamphetamine caused varying degrees of reduction in the numerical density in several forebrain regions. A high decrement (over -90%) was found in deep layers of the cerebral cortex, striatum and thalamic paraventricular nucleus, while a less prominent reduction (about -50%) was seen in such regions as the suprachiasmatic nucleus and basolateral amygdaloid nucleus. Moreover, superficial layers of the cerebral cortex contained uncommon features of immunopositive axons which were characterized by intensely stained fibers with large varicosities. The results suggest that the rat forebrain contains at least two types of serotonin nerves, one very sensitive to methamphetamine and another relatively insensitive or resistant to it.


[Effect of bismuth glycyrrhizate on experimental gastric ulcers and its mechanisms].
To investigate the ulcer-preventive effect of bismuth glycyrrhizate on experimental gastric ulcer and its mechanisms. Three kinds of model animals with experimental gastric ulcer were established and gastric mucosal injuries were induced by pyloric ligation in rats, applying ethanol in rats and imposing stress in mice, respectively. The rats were divided into experimental groups treated with bismuth glycyrrhizat 700, 350, 175 mg kg(-1), positive control group treated with cimetidine (200 mg kg(-1), and negative control group treated with 0.1% EDTA. The mice were divided into experimental groups treated with bismuth glycyrrhiza 980, 490, 250 mg kg(-1). The gastric ulcer index, gastric juice volume, acidity, pepsin activity, the level of nitric oxide (NO) in serum and the level of prostaglandin E2 in gastric tissue were measured in rats. Bismuth glycyrrhizate was shown to be able to reduce the gastric juice volume, acidity and pepsin activity as well as gastric ulcer index. It could increase the content of NO in serum and the content of prostaglandin E2 in gastric tissue. The bismuth glycyrrhizate has antiulcer effect in rats.


Recent Approaches of Repositioning and Traditional Drugs for the Treatment of COVID-19 Pandemic Outbreak.
The recent emergence of novel, pathogenic COVID-19 disease associated with SARSCoV- 2 virus in China and its rapid national and international spread pose a global health emergency. The development of a new drug is tedious and may take decades to develop and involve multiple steps like the development of prototypes and phase I to III human trials, which involve the study on small to large populations to examine the safety and side effects associated with the drug under trials. Due to continous increase in the number of confirmed cases and deaths, there is an urgent need to develop a drug that is effective to kill the SARS-CoV-2 virus with fewer side effects to the human body. Therefore, this review focus on the latest advances in the development for the treatment of COVID-19 disease associated with SARS-CoV-2 with repositioning of already marketed drug with small molecules, as well as Chinese traditional medicines with established safety and efficacy which are being used for different therapeutic uses.


Permanent improvement in deficient sensory inhibition in DBA/2 mice with increased perinatal choline.
Schizophrenia patients and certain inbred mouse strains (i.e., DBA/2) show deficient sensory inhibition which has been linked to reduced numbers of hippocampal alpha7 nicotinic receptors and to underlying polymorphisms in the promoter region for the alpha7 gene. Increasing maternal dietary choline, a selective alpha7 agonist, during gestation has been shown to produce long-term changes in adult offspring behavior (i.e., improved learning and memory in rats). The objective of this study is to improve sensory inhibition in DBA/2 mice through maternal choline supplementation. DBA/2 dams were placed on normal (1.1 g/kg) or supplemented (5 g/kg) choline diet throughout gestation and lactation. Offspring were placed on normal diet at weaning and were assessed for sensory inhibition parameters at adulthood. Evoked EEG responses to identical paired auditory stimuli were compared. At the end of the study, the brains were collected for autoradiographic assessment of hippocampal levels of alpha-bungarotoxin binding to visualize alpha7 nicotinic receptors. Offspring mice which were choline supplemented during gestation showed significantly improved sensory inhibition compared to mice gestated on the normal choline diet. The improvement was produced by a significant reduction in the response to the second stimulus, demonstrating improved inhibition to that stimulus. There was a concurrent increase in alpha7 receptor numbers in both the CA1 and dentate gyrus regions of the hippocampus suggesting that this increase may be responsible for the improved inhibition. These data show that gestational choline supplementation produces permanent improvement in a deficit associated with schizophrenia and may have implications for human prenatal nutrition.


Correction to: Treating COVID-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind Randomized Controlled Trial in Hospitalized Patients.
[This corrects the article DOI: 10.1093/ofid/ofaa446.].


Serotonergic and noradrenergic receptors in the rat brain: modulation by chronic exposure to ovarian hormones.
Noradrenergic (alpha 1 and beta) and serotonergic (5HT1 and 5HT2) receptors were assayed in the brains of ovariectomized female rats treated for 2 weeks with estrogen, progesterone or a combination of both hormones. Estrogen treatment resulted in a decrease in the number of 5HT1 and beta adrenergic receptors, with a concomitant increase in 5HT2 receptors. Progesterone alone caused a smaller increase in 5HT2 receptors, a similar decrease in 5HT1 and had no significant effect on noradrenergic receptors. When given with estrogen, progesterone blocked the estrogen effect on 5HT2 receptors but did not inhibit the estrogen-mediated decrease in 5HT1 and beta adrenergic receptors. alpha 1 adrenergic receptors were not affected by any of the hormone treatment paradigms. beta adrenergic and 5HT2 receptors are often implicated in antidepressant action, and the modulation of these two receptor types by ovarian hormones might be relevant to hormone-linked affective changes such as premenstrual tension and post-partum depression.


Influence of non-thermal TiCl4/Ar+O2 plasma-assisted TiOx based coatings on the surface of polypropylene (PP) films for the tailoring of surface properties and cytocompatibility.
The superior bulk properties (corrosion resistance, high strength to weight ratio, relatively low cost and easy processing) of hydrocarbon based polymers such as polypropylene (PP) have contributed significantly to the development of new biomedical applications such as artificial organs and cell scaffolds. However, low cell affinity is one of the main draw backs for PP due to its poor surface properties. In tissue engineering, physico-chemical surface properties such as hydrophilicity, polar functional groups, surface charge and morphology play a crucial role to enrich the cell proliferation and adhesion. In this present investigation TiOx based biocompatible coatings were developed on the surface of PP films via DC excited glow discharge plasma, using TiCl4/Ar+O2 gas mixture as a precursor. Various TiOx-based coatings are deposited on the surface of PP films as a function of discharge power. The changes in hydrophilicity of the TiOx/PP film surfaces were studied using contact angle analysis and surface energy calculations by Fowke's approximation. X-ray photo-electron spectroscopy (XPS) was used to investigate the surface chemical composition of TiOx/PP films. The surface morphology of the obtained TiOx/PP films was investigated by scanning electron and transmission electron microscopy (SEM &TEM). Moreover, the surface topography of the material was analyzed by atomic force microscopy (AFM). The cytocompatibility of the TiOx/PP films was investigated via in vitro analysis (cell viability, adhesion and cytotoxicity) using NIH3T3 (mouse embryonic fibroblast) cells. Furthermore the antibacterial activities of TiOx/PP films were also evaluated against two distinct bacterial models namely Gram positive Staphylococcus aureus (S.aureus) and Gram negative Escherichia coli DH5α. (E.coli) bacteria. XPS results clearly indicate the successful incorporation of TiOx and oxygen containing polar functional groups on the surface of plasma treated PP films. Moreover the surface of modified PP films exhibited nano structured morphology, as confirmed by SEM, TEM and AFM. The physico-chemical changes have improved the hydrophilicity of the PP films. The in-vitro analysis clearly confirms that the TiOx coated PP films performs as good as the standard tissue culture plates and also are unlikely to impact the bacterial cell viability.


Agent-based modeling of porous scaffold degradation and vascularization: Optimal scaffold design based on architecture and degradation dynamics.
A multi-layer agent-based model (ABM) of biomaterial scaffold vascularization is extended to consider the effects of scaffold degradation kinetics on blood vessel formation. A degradation model describing the bulk disintegration of porous hydrogels is incorporated into the ABM. The combined degradation-angiogenesis model is used to investigate growing blood vessel networks in the presence of a degradable scaffold structure. Simulation results indicate that higher porosity, larger mean pore size, and rapid degradation allow faster vascularization when not considering the structural support of the scaffold. However, premature loss of structural support results in failure for the material. A strategy using multi-layer scaffold with different degradation rates in each layer was investigated as a way to address this issue. Vascularization was improved with the multi-layered scaffold model compared to the single-layer model. The ABM developed provides insight into the characteristics that influence the selection of optimal geometric parameters and degradation behavior of scaffolds, and enables easy refinement of the model as new knowledge about the underlying biological phenomena becomes available. This paper proposes a multi-layer agent-based model (ABM) of biomaterial scaffold vascularization integrated with a structural-kinetic model describing bulk degradation of porous hydrogels to consider the effects of scaffold degradation kinetics on blood vessel formation. This enables the assessment of scaffold characteristics and in particular the disintegration characteristics of the scaffold on angiogenesis. Simulation results indicate that higher porosity, larger mean pore size, and rapid degradation allow faster vascularization when not considering the structural support of the scaffold. However, premature loss of structural support by scaffold disintegration results in failure of the material and disruption of angiogenesis. A strategy using multi-layer scaffold with different degradation rates in each layer was investigated as away to address this issue. Vascularization was improved with the multi-layered scaffold model compared to the single-layer model. The ABM developed provides insight into the characteristics that influence the selection of optimal geometric and degradation characteristics of tissue engineering scaffolds.


The prevalence and risk factors of menstrual pain of married women in Anhui Province, China.
To investigate the prevalence and the associated risk factors for menstrual pain in a sample of rural married women of reproductive age in Anhui Province of China. A cross-sectional study was conducted among married women (n = 14,828) aged 18-45 years. Data were collected through self-reported questionnaires. Mann Whitney U, Kruskal-Walls H tests and ordinal logistic regression models were used to analyze the data. The prevalence of no, moderate, severe menstrual pain was 80.1%, 18.7%, 1.2%, respectively. Lower educational level, lower stress level and earlier age at menarche were protective factors for menstrual pain while women with longer duration of menstrual flow tended to have menstrual pain. Compared to women with a normal body mass index (BMI), significantly higher odds of reporting menstrual pain were detected for women who were lower BMI or higher BMI. Age, length of menstrual cycle, blood type, anemia and previous pregnancy were not significantly associated with dysmenorrhea after controlling for potential confounding factors. There is high prevalence of dysmenorrhea among women in China. Our results suggest that reduction of stress and maintaining a normal BMI may be important for women to have pain-free periods.


Antenatal Surveillance in Twin Pregnancies Using the Biophysical Profile.
Objectives-The nonstress test is currently the most widely used modality for antenatal surveillance in twin pregnancies, with a quoted false-positive rate of 11%-12%. Our objective was to report our experience with the sonographic portion of the biophysical profile in twin pregnancies as the primary screening modality.Methods-Women with twin pregnancies delivered by a single maternal-fetal medicine practice from 2005 to 2013 were included. We excluded monoamniotic twins. Twin pregnancies began weekly sonography for the biophysical profile starting at 32 to 33 weeks, or earlier if indicated. The nonstress test was performed if the sonographic biophysical profile score was less than 8 of 8. We reviewed biophysical profile scores and outcomes for all patients who delivered at 33 weeks or later to assess the false-positive rate for the biophysical profile, as well as the incidence of intrauterine fetal death (IUFD) after initiation of antenatal surveillance.Results-A total of 539 twin pregnancies were included. The incidence of IUFD per patient was 2 per 539 (0.4%; 95% confidence interval [CI], 0.1%-1.3%), and the incidence of IUFD per fetus was 2 per 1078 (0.19%; 95% CI, 0.05%-0.7%). The overall positive screen rate was 24 per 539 (4.45%; 95% CI, 3.0%-6.5%). The false-positive screen rate, defined as an abnormal biophysical profile that did not diagnose an IUFD or lead to delivery, was 10 per 539 (1.9%; 95% CI, 1.0%-3.4%).Conclusions-In twin pregnancies the use of the sonographic biophysical profile for routine antenatal surveillance has a low false-positive rate, with a very low incidence of IUFD. The sonographic biophysical profile should be considered as a primary mode for antenatal surveillance in twin pregnancies, with a reflex nonstress test for an abnormal score.


Recombinant bovine spleen myristoyl CoA: protein N-myristoyltransferase.
Myristoyl-CoA:protein N-myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyzes the co-translational transfer of myristate to the NH2-terminal glycine residue of a number of important proteins of diverse function. Recently, we have isolated full length cDNA encoding bovine spleen NMT [27] the full length cDNA was cloned and expressed in E. coli, resulting in the expression of functionally active 50 kDa NMT. Using the combination of SP-Sepharose fast flow and Mono S fast protein liquid chromatography, the enzyme was purified 20-fold with a high yield. The spleen NMT (sNMT) fusion protein exhibited an apparent molecular weight of 53 kDa on SDS-PAGE. Upon cleavage by the Enterokinase the sNMT exhibited an apparent molecular weight of 50 kDa without loss of catalytic activity. The two synthetic peptide substrates based on the N-terminal sequence of pp60src (GSSKSKMR) and cAMP dependent protein kinase (GNAAAKKRR) have different kinetic parameters of Km values of 40 and 200 microM. Recombinant sNMT was also potently inhibited by Ni2+ (histidine binder) in a concentration dependent manner with a half maximal inhibition of 280 microM. The E. coli expressed sNMT was homogenous and showed enzyme activity.


Residential needs in hospital and the community for mentally handicapped people.
Using successive analyses of hospitalized mentally handicapped people from a geographically defined Welsh catchment area, this article attempts to evaluate changes in cohorts of such patients. It suggests the likelihood that the level of hospital accommodation predicted in the White Paper "Better Services for the Mentally Handicapped" will be sufficient.


Erratum: Aldehyde dehydrogenase 1A1 confers erlotinib resistance via facilitating the reactive oxygen species-reactive carbonyl species metabolic pathway in lung adenocarcinomas: Erratum.
[This corrects the article DOI: 10.7150/thno.35729.].


Roles of the peroxisome proliferator-activated receptors (PPARs) in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease phenotypes which start with simple steatosis and lipid accumulation in the hepatocytes - a typical histological lesions characteristic. It may progress to non-alcoholic steatohepatitis (NASH) that is characterized by hepatic inflammation and/or fibrosis and subsequent onset of NAFLD-related cirrhosis and hepatocellular carcinoma (HCC). Due to the central role of the liver in metabolism, NAFLD is regarded as a result of and contribution to the metabolic abnormalities seen in the metabolic syndrome. Peroxisome proliferator-activated receptors (PPARs) has three subtypes, which govern the expression of genes responsible for energy metabolism, cellular development, inflammation, and differentiation. The agonists of PPARα, such as fenofibrate and clofibrate, have been used as lipid-lowering drugs in clinical practice. Thiazolidinediones (TZDs) - ligands of PPARγ, such as rosiglitazone and pioglitazone, are also used in the treatment of type 2 diabetes (T2D) with insulin resistance (IR). Increasing evidence suggests that PPARβ/δ agonists have potential therapeutic effects in improving insulin sensitivity and lipid metabolism disorders. In addition, PPARs ligands have been considered as potential therapeutic drugs for hypertension, atherosclerosis (AS) or diabetic nephropathy. Their crucial biological roles dictate the significance of PPARs-targeting in medical research and drug discovery. Here, it reviews the biological activities, ligand selectivity and biological functions of the PPARs family, and discusses the relationship between PPARs and the pathogenesis of NAFLD and metabolic syndrome. This will open new possibilities for PPARs application in medicine, and provide a new idea for the treatment of fatty liver and related diseases.


Evaluation of liver fat in the presence of iron with MRI using T2* correction: a clinical approach.
To assess magnetic resonance imaging (MRI) with conventional chemical shift-based sequences with and without T2* correction for the evaluation of steatosis hepatitis (SH) in the presence of iron. Thirty-one patients who underwent MRI and liver biopsy because of clinically suspected diffuse liver disease were retrospectively analysed. The signal intensity (SI) was calculated in co-localised regions of interest (ROIs) using conventional spoiled gradient-echo T1 FLASH in-phase and opposed-phase (IP/OP). T2* relaxation time was recorded in a fat-saturated multi-echo-gradient-echo sequence. The fat fraction (FF) was calculated with non-corrected and T2*-corrected SIs. Results were correlated with liver biopsy. There was significant difference (P < 0.001) between uncorrected and T2* corrected FF in patients with SH and concomitant hepatic iron overload (HIO). Using 5 % as a threshold resulted in eight false negative results with uncorrected FF whereas T2* corrected FF lead to true positive results in 5/8 patients. ROC analysis calculated three threshold values (8.97 %, 5.3 % and 3.92 %) for T2* corrected FF with accuracy 84 %, sensitivity 83-91 % and specificity 63-88 %. FF with T2* correction is accurate for the diagnosis of hepatic fat in the presence of HIO. Findings of our study suggest the use of IP/OP imaging in combination with T2* correction. • Magnetic resonance helps quantify both iron and fat content within the liver • T2* correction helps to predict the correct diagnosis of steatosis hepatitis • "Fat fraction" from T2*-corrected chemical shift-based sequences accurately quantifies hepatic fat • "Fat fraction" without T2* correction underestimates hepatic fat with iron overload.


Application of Ribosomal Internal Transcribed Spacer 1, Internal Transcribed Spacer 2, and Large-Subunit D1-D2 Regions as the Genetic Markers to Identify Fungi Isolated from Different Environmental Samples: A Molecular Surveillance Study of Public Health Importance.
In September 2012, a multistate fungal meningitis outbreak started across 20 states in the United States. It affected 753 individuals and caused 64 deaths who received contaminated spinal injections. In a previous study, we analyzed 26 environmental samples collected from the manufacturing premises of a compounding company to determine the possible cause of an outbreak and identified 14 distinct fungal species. In this follow-up study, we have analyzed 198 environmental samples collected from three additional compounding company premises located in the United States for the presence of pathogenic fungi. Environmental swab samples were initially examined by standard microbiological methods. Subsequently, DNA sequencing was performed on all of the 25 recovered fungal isolates at the D1-D2 domain of the large subunit (LSU) ribosomal RNA (rRNA) and the internal transcribed spacer (ITS) regions. Sequence analysis of the ITS1, ITS2, and LSU rRNA regions confirmed the presence of the following fungal species in the environmental samples analyzed: (i) Pestalotiopsis cocculi from the region Ia; (ii) Epicoccum nigrum and Trichaptum biforme from the region Ib; (iii) Nigrospora sphaerica and Fusarium sp. from the region II; and (iv) Curvularia sp., Fusarium sp., Penicillium sp., and Preussia sp. from the region III. Species identification of 25 recovered fungal isolates matched, in most cases, at 3 sequenced loci (ITS1, ITS2, and LSU). DNA sequencing of ITS1, ITS2, and LSU D1-D2 regions can be used to perform fungal typing and in implementing effective environmental monitoring programs of public health importance.


Ultrastructure of a cephalic sensory organ in larvae of the gastropod Phestilla sibogae (Aeolidacea, Nudibrachia).
The cephalic sensory organ is a superficial sensory receptor located between the velar lobes at the level of the shell aperture. Three cell types make up this sensory area: (1) six flask-shaped cells bearing numerous cilia: (2) adjacent supporting or accessory cells which have numerous, often branched, microvilli; and (3) vacuolated cells which occupy the center of the area. The flask-shaped cells appear to be the sensory units. These cells have a deep invaginated lumen, with ciliar arising from the cell surface in the lumen oriented either toward the base of the lumen or toward the epidermal surface these cilia, some of which extend slightly above the body surface, are presumed to be non-motile, as they lack (dynein?) arms on the axonemal A tubules and lack striated rootlets. The six flask cells are in intimate contact with the underlying cerebral ganglia and axons from each cell pass into ganglionic tissue. The supporting cells may be sensory, but no direct connection with the nervous system was seen. The function of the central vacuolated cells is not known. This cephalic organ may be a derivative of the original apical tuft of the trochophore stage.


Contraction of isolated airway smooth muscle by synthetic leukotrienes C4 and D4.
The pharmacology of leukotrienes (LT) C4 and D4 in isolated airway smooth muscle was investigated. In rat trachea, neither LTC4 or D4 elicited a response. In contrast, LTC4 was a potent contractile agonist in guinea-pig trachea, bronchus and parenchymal lung strip. Similar effects were obtained with LTD4 in trachea and parenchyma. In trachea and bronchus, the concentration-response curve to LTC4 was biphasic: indomethacin converted the biphasic response curve to a simple sigmoidal shape and enhanced the maximum contractile response. The SRS-A antagonist FPL 55712 antagonized the effect of LTD4 in both trachea and parenchyma. As regards LTC4-induced contraction of trachea and bronchus, FPL 55712, depending on concentration, either antagonized, or antagonized and enhanced the maximum contractile response. The enhancement of the maximum contractile response by FPL 55712 was not apparent when indomethacin was present. FPL 55712 failed to antagonize the effect of LTC4 in parenchyma.


Effects of Gestational Intermittent Hypoxia on Placental Morphology and Fetal Development in a Murine Model of Sleep Apnea.
Obstructive sleep apnea (OSA) during pregnancy is characterized by episodes of intermittent hypoxia (IH) during sleep, resulting in adverse health outcomes for mother and offspring. Despite a prevalence of 8-20% in pregnant women, this disorder is often underdiagnosed.We have developed a murine model of gestational OSA to study IH effects on pregnant mothers, placentas, fetuses, and offspring. One group of pregnant rats was exposed to IH during the last 2 weeks of gestation (GIH). One day before the delivery date, a cesarean section was performed. Other group of pregnant rats was allowed to give birth at term to study offspring's evolution.Preliminary results showed no significant weight differences in mothers and fetuses. However, the weight of GIH male offspring was significantly lower than the controls at 14 days (p < 0.01). The morphological study of the placentas showed an increase in fetal capillary branching, expansion of maternal blood spaces, and number of cells of the external trophectoderm in the tissues from GIH-exposed mothers. Additionally, the placentas from the experimental males were enlarged (p < 0.05). Further studies are needed to follow the long-term evolution of these changes to relate the histological findings of the placentas with functional development of the offspring in adulthood.


Synthesis of five and six-membered heterocycles bearing an arylpiperazinylalkyl side chain as orally active antinociceptive agents.
A number of heterocycles bearing an arylpiperazinylalkyl side chain and structurally related to the previously described lead ET1 (4-amino-6-methyl-2-[3-(4-p-tolylpiperazin-1-yl)propyl]-5-vinylpyridazin-3(2H)-one) was synthesized and tested for their antinociceptive activity in Writhing Test. Many compounds, tested at doses of 20-40 mg/kg po were able to reduce the number of abdominal constrictions by more than 47% and, in same cases, the potency is comparable to lead ET1 as for 5e, 24a, 27b and 27c. The analgesia induced by the active compounds was completely prevented by pretreatment with α2-antagonist yohimbine, confirming the involvement of the adrenergic system in the mechanism of action for these new compounds.


Effects of novel taxanes SB-T-1213 and IDN5109 on tubulin polymerization and mitosis.
SB-T-1213 and IDN5109 are semisynthetic, orally available taxanes that are up to 400-fold more active than paclitaxel against drug-resistant cells. IDN5109 is in clinical trials. We investigated the primary target for SB-T-1213 and IDN5109 and whether the compounds interact with microtubules differently than paclitaxel. Unlike paclitaxel, at 1-10 microM both novel taxanes initiate microtubule polymerization in vitro with no lag. They enhance polymerization equally or more potently than paclitaxel. SB-T-1213 induces unusual microtubules with attached extra protofilaments or open sheets, and IDN5109 induces large protofilamentous sheets. Both inhibit HeLa cell proliferation, block mitosis at the metaphase/anaphase transition, bundle microtubules at high drug concentrations, and induce abnormal metaphase spindles and apoptosis. They target microtubules but alter their polymerization and structure differently than paclitaxel. These differences may play a role in their enhanced cytotoxicity and efficacy.


Histologically proven venous congestive myelopathy without concurrent vascular malformation: Case reports and review of the literature.
Venous congestive myelopathy is a progressive myelopathy that is generally caused by a spinal dural arteriovenous fistula. We report a patient with histologically confirmed venous congestive myelopathy without concurrent vascular malformations in radiological and intraoperative findings. The definitive underlying etiology of this congestive myelopathy was unclear. However, this case report highlights the possibility of venous congestive myelopathy with etiology other than a dural arteriovenous fistula. Further, a systematic and elaborate examination should be undertaken to explore the underlying pathology whenever this type of spinal parenchymal lesion is detected.


Mechanistic insights into RNase L through use of an MDMX-derived multi-functional protein domain.
RNase L is part of the innate immune response to viral infection. It is activated by a small oligonucleotide (2-5A) whose synthesis is initiated as part of the interferon response. Binding of 2-5A to the N-terminal regulatory region, the ANK domain, of RNase L activates its ribonuclease activity and results in cleavage of RNA in the cell, which ultimately leads to apoptosis of the infected cell. The mechanism by which 2-5A activates the ribonuclease activity of RNase L is currently unclear but 2-5A has been shown to induce dimerization of RNase L. To investigate the importance of dimerization of RNase L, we developed a 15kDa dimerization-inducing protein domain that was fused to the N-terminus of RNase L. From these studies we provide direct evidence that dimerization of RNase L occurs at physiologically relevant protein concentrations and correlates with activation of ribonuclease activity. We also show that the binding of 2-5A to RNase L promotes dimerization of the ANK domain and suggest how this could transmit a signal to the rest of the protein to activate ribonuclease activity. Finally, we show that the dimerization-inducing domain can be used as a general fusion partner to aid in protein expression and purification.


The effect of density upon deposit-feeding populations: Movement, feeding and floating of Hydrobia ventrosa Montagu (Gastropoda: Prosobranchia).
Crawling rate, feeding rate and floating frequency were measured for laboratory populations of the deposit-feeding snail Hydrobia ventrosa at densities of 0.3-16 snails cm-2. Both movement and feeding were depressed with increasing density. However, floating increased with increasing density. Crowding effects are thus important in deposit-feeding populations and must be considered along with resource-renewal in considerations of population control. Floating may be an adaptation to escape crowded conditions.


A dolichyl phosphate-cleaving acid phosphatase from Tetrahymena pyriformis.
Tetrahymena pyriformis contains an enzyme which hydrolyzed dolichyl phosphate. This activity was solubilized from lyophilized samples of this organism and was relatively stable when stored frozen. The soluble enzyme preparation had an acid pH optimum and hydrolyzed both dolichyl and phytanyl phosphates at equivalent rates. The polyprenylphosphate phosphatase activity was compared with the acid phosphatases which hydrolyzed p-nitrophenyl phosphate and marked differences were found. Dolichyl phosphate hydrolysis required Mg2+ for maximum activity while the bulk of the phosphatase activity was not effected by the absence of this ion. Other differences were that the polyprenylphosphate phosphatase was relatively insensitive to inhibitors such as tartrate and vanadium oxide sulfate which had a pronounced effect on the rate of p-nitrophenyl phosphate hydrolysis. The two activities also appeared to have different subcellular distributions. The polyprenylphosphate phosphatase was markedly inhibited by ethoxy formic anhydride, a reagent which is active against enzymes containing a histidine residue at their active site, while p-nitrophenyl phosphate hydrolysis was unaffected. The polyprenylphosphate phosphatase may be important in regulating the level of dolichyl phosphate in T. pyriformis and thus the rate of glycoprotein synthesis. It is also a useful tool which is capable of liberating dolichol from dolichyl phosphate under mild conditions which will permit the further characterization of the polyprenols.


Synthesis and Anti-Candida Activity of Cobalt(II) Complexes of Benzene-1,2-Dioxyacetic Acid (bdoaH(2)). X-Ray Crystal Structures of [Co(bdoa)(H(2)O)(3)] 3.5H(2)O and {[CO(phen)(3)](bdoa)}(2)24H(2)O (phen = 1,10-Phenanthroline).
Co(CH(3)CO(2))(2)4H(2)O reacts with benzene-1,2-dioxyacetic acid (bdoaH(2)) to give the Co(2+) complexes [Co(bdoa)(H(2)O)(3)]H(2)O (1a) and [Co(bdoa)(H(2)O)(3)] 3.5H(2)O (1b). Subsequent reaction of 1a with 1,10- phenanthroline produces [CO(phen)(3)] bdoa10H(2)O (2a) and {[CO(phen)(3)](bdoa)}(2)24H(2)O (2b). Molecular structures of 1b and 2b were determined crystallographically. In 1b the bdoa(2-)- ligates the metal by two carboxylate oxygens and two ethereal oxygens, whereas in 2b the bdoa(2-) is uncoordinated. The Mn(2+) and Cu(2+) complexes [Mn(bdoa)(phen)(2)]H(2)O (3) and [Cu(pdoa)(imid)(2)] (4) were also synthesised, 1a-4 and other metal complexes of bdoa H(2) (metal = Mn(2+), Co(2+) ,Cu(2+), Cu(+) ) were screened for their ability to inhibit the growth ofhe yeast Candida albicans. Complexes incorporating the 1,10-phenanthroline ligand were the most active.


Arterial mechanics considering the structural and mechanical contributions of ECM constituents.
Considering the organization and engagement behavior of different extracellular matrix (ECM) constituents in the medial and adventitial layer of the arterial wall, in this study, we proposed a new constitutive model of ECM mechanics that considers the distinct structural and mechanical contributions of medial elastin, medial collagen, and adventitial collagen, to incorporate the constituent-specific fiber orientation and the sequential fiber engagement in arterial mechanics. Planar biaxial tensile testing method was used to characterize the orthotropic and hyperelastic behavior of porcine thoracic aorta. Fiber distribution functions of medial elastin, medial collagen, and adventitial collagen were incorporated into the constitutive model. Considering the sequential engagement of ECM constituents in arterial mechanics, a recruitment density function was incorporated into the model to capture the delayed engagement of adventitial collagen. A freely jointed chain model was used to capture the mechanical behavior of elastin and collagen at the fiber level. The tissue-level ECM mechanics was obtained by incorporating fiber distribution, engagement, and elastin and collagen content. The multi-scale constitutive model considering the structural and mechanical contributions of the three major ECM constituents allows us to directly incorporate information obtained from quantitative multi-photon imaging and analysis, and biochemical assay for the prediction of tissue-level mechanical response. Moreover, the model shows promises in fitting and predicting with a small set of material parameters, which has physical meanings and can be related to the structure of the ECM.


Broad HPV distribution in the genital region of men from the HPV infection in men (HIM) study.
The HPV infection in men (HIM) study examines the natural history of genital HPV infection in men. Genotyping methods used in this study identify 37 α-HPV types; however, the viral type could not be identified in approximately 22% of male genital specimens that were HPV PCR positive. Our aim was to genotype HPV-unclassified specimens by sequencing PGMY09/11, GP5+/6+ or FAP59/64 PCR products. Using this approach we were able to detect 86 unique HPV types among 508 of 931 specimens analyzed. We report for the first time the presence of a broad range of α-, β- and γ-HPV at the male genitals.


The relation of alcohol consumption and cigarette smoking to the multiple occurrence of esophageal dysplasia and squamous cell carcinoma.
The unique pathologic features of esophageal tumors in patients with esophageal cancer includes the presence of multiple occurrence within the esophagus. The aim of this study is to clarify the molecular mechanism of carcinogenesis of multiple esophageal squamous cell carcinomas in the Japanese. We studied the relationship between the incidence of patients with multiple carcinomas and the coexistence of dysplasia lesions with p53 protein accumulation, alcohol consumption, and cigarette smoking. Among 76 cancer lesions and 60 cases of dysplasia, p53 accumulation was studied by means of immunohistochemical analysis. The incidence of patients with multiple carcinomas in the high-risk group was 33%, and the incidence of patients with a coexistence of dysplasia in the high-risk group was 67%. The incidence of patients with multiple carcinomas or the coexistence of dysplasia in the high-risk group was much higher than that of the middle-risk and low-risk groups (P <.0001 and P =.04, respectively). The average number of abnormal epitheliums, such as cancer and dysplasia, in the high-risk group was 3.2 +/- 2.1. The average number of abnormal epitheliums was much higher than that of the other groups (P =.02). For carcinoma lesions, the incidence of lesions with a positive p53 protein accumulation in the high-risk group was 91%. Regarding dysplasia lesions, the incidence of lesions with a positive p53 protein accumulation in the high-risk group was 80%. The incidence of both cancer and dysplasia lesions with a positive p53 protein accumulation in the high-risk group was higher than that of the other groups. The pattern of p53 accumulation in dysplasia in the high-risk group was closely similar to that in cancer of the high-risk group. These findings support the concept of field carcinogenesis of the esophagus.


Blood pressure mediated the effects of cognitive function impairment related to aluminum exposure in Chinese aluminum smelting workers.
The aim of this study is to investigate the effects that the Al on blood pressure and the effect of hypertension in aluminum-induced cognitive impairment in electrolytic aluminum worker. The study was conducted 392 male aluminum electrolytic workers in an aluminum plant of China. The concentration of alumina dust in the air of the electrolytic aluminum workshop is 1.07 mg/m3-2.13 mg/m3. According to the Permissible concentration-Time Weighted Average of alumina dust is 4 mg/m3, which does not exceed the standard. The blood pressure of the workers was measured. The plasma aluminum concentration of workers was determined by ICP-MS (Inductively Coupled Plasma Mass Spectrometry). Cognitive functions were measured using MMSE (Mini-Mental State Examination), VFT (Verbal Fluency Test), ATIME (Average Reaction Time), FOM (Fuld Object Memory Evaluation), DST (Digit Span Test), CDT (Clock Drawing Test) scales. Modified Poisson regression was used to analyze the risk of hypertension and cognitive impairment with different plasma aluminum concentrations. Generalized linear regression model was used to analyze the relationship between aluminum and cognitive function, blood pressure and cognitive function. Causal Mediation Analysis was used to analyze the mediation effect of blood press in aluminum-induced cognitive impairment. Plasma aluminum appeared to be a risk factor for hypertension (PR (prevalence ratio) = 1.630, 95 %-CI (confidence interval): 1.103-2.407), systolic blood pressure (PR = 1.578, 95 %-CI: 1.038-2.399) and diastolic blood pressure (PR = 1.842, 95 %-CI: 1.153-2.944). And plasma aluminum increased by e-fold, the scores of MMSE and VFT decreased by 0.630 and 2.231 units respectively and the time of ATIME increased by 0.029 units. In addition, generalized linear regression model showed that blood press was negatively correlated with the scores of MMSE and VFT. Finally, causal Mediation Analysis showed that hypertension was a part of the mediating factors of aluminum-induced decline in MMSE score, and the mediating effects was 16.300 % (7.100 %, 33.200 %). In addition, hypertension was a part of the mediating factors of aluminum-induced decline in VFT score, and the mediating effects was 9.400 % (2.600 %, 29.000 %) CONCLUSION: Occupational aluminum exposure increases the risk of hypertension and cognitive impairment. And hypertension may be a mediating factor of cognitive impairment caused by aluminum exposure.


inv(12)(p11.2q13) in an endometrial polyp.
A benign endometrial polyp from a 50-year-old postmenopausal woman has been cytogenetically investigated. A single clonal karyotypic anomaly, inv(12)(p11.2q13), was found in about 30% of cells analyzed after short-term culture. This finding contributes further to the hypothesis that the chromosomal segment 12q13-q14, which is also involved in chromosomal rearrangements in uterine leiomyomas, pleomorphic adenomas of the salivary glands, lipomas, and myxoid liposarcomas, contains a gene or genes that are related to cellular proliferation rather than to malignant transformation.


Epithelioid Angiomyolipoma in a Pediatric Patient: Case Report and Review of Literature.
We report a case of a 17-year-old girl with tuberous sclerosis complex who underwent partial nephrectomy for a newly discovered 7.5-cm renal mass subsequently determined to be an epithelioid angiomyolipoma, a rare variant of angiomyolipoma that can be confused clinically, radiographically, and pathologically for renal cell carcinoma. Proper diagnosis and treatment are critical, especially in the pediatric patient. This case report and review of literature serve at increasing the awareness of this renal tumor, with its somewhat unpredictable outcome, reviewing the pertinent literature on the topic of epithelioid angiomyolipoma in the clinical setting of tuberous sclerosis complex.


Elucidating the role of metal ions in carbonic anhydrase catalysis.
Why metalloenzymes often show dramatic changes in their catalytic activity when subjected to chemically similar but non-native metal substitutions is a long-standing puzzle. Here, we report on the catalytic roles of metal ions in a model metalloenzyme system, human carbonic anhydrase II (CA II). Through a comparative study on the intermediate states of the zinc-bound native CA II and non-native metal-substituted CA IIs, we demonstrate that the characteristic metal ion coordination geometries (tetrahedral for Zn2+, tetrahedral to octahedral conversion for Co2+, octahedral for Ni2+, and trigonal bipyramidal for Cu2+) directly modulate the catalytic efficacy. In addition, we reveal that the metal ions have a long-range (~10 Å) electrostatic effect on restructuring water network in the active site. Our study provides evidence that the metal ions in metalloenzymes have a crucial impact on the catalytic mechanism beyond their primary chemical properties.


Diastereochemical differentiation of some cyclic and bicyclic beta-amino acids, via the kinetic method.
Stereochemical differentiation of five diastereomeric pairs of beta-amino acids, di-endo- and di-exo-2,3-disubstituted norbornane and norbornene amino acids, cis- and trans-2-aminocyclohexane-, 2-amino-4-cyclohexene-, and 2-aminocyclopentanecarboxylic acids, was investigated via the kinetic method with metal-bound trimeric complexes. This is the first time that diastereomers (di-endo/di-exo and cis/trans) have been differentiated with metal-bound trimeric complexes and the kinetic method. Moreover, determination of diastereochemical excess by the kinetic method was applied to norbornane beta-amino acids and cyclopentane beta-amino acids. Experiments showed that a remarkable differentiation of the studied diastereomers was achieved. It was observed that better selectivity values correlated to more rigid structures. The reference compounds for the studied beta-amino acids varied from alpha-amino acids to some beta-amino acids. In addition, variation of the metal ion (Cu(2+) and Ni(2+)) had some role in the selectivity values obtained. Ab initio and hybrid density functional theory calculations were performed to clarify the results obtained by mass spectrometry.


Partial ulnar nerve transfer to the branch of the long head of the triceps to recover elbow extension in C5, C6 and C7 brachial plexus palsy.
Elbow flexion is the first goal in upper partial brachial plexus palsy treatment. However, elbow extension is essential for daily living activities. To recover this function, one fascicle of ulnar nerve can be transferred to the branch of the long head of the triceps, but this procedure has been previously published in only two patients. The goal of our study is to assess a larger series of transfers of one fascicle of ulnar nerve to the branch of the long head of the triceps to help patients recover elbow extension. Ten male patients with C5, C6 and C7 brachial plexus injuries underwent operation. For shoulder recovery, we transferred the spinal accessory nerve and rhomboid nerve. For elbow flexion, one fascicle of median nerve was transferred to the nerve of the biceps. For elbow extension, we transferred one fascicle of ulnar nerve to the branch of the long head of the triceps. Tendon transfers were performed for wrist and finger extension. Nine patients recovered M4 elbow flexion and extension. One patient had M3 elbow extension and flexion. Average active shoulder elevation was 85° and average active shoulder external rotation was 65° All patients recovered finger and wrist extension. The classical techniques of grafts or phrenic or intercostal nerve transfers to recover elbow extension are not always reliable, according to the literature. Because the harvested ulnar nerve motor fascicle is close to the branch of the long head of the triceps, the recovery time for this procedure is shorter than that of other described nerve transfers. The isolated recovery of the reinnervated long head of the triceps muscle excludes spontaneous recovery occasionally noted in upper root plexus injuries. The transfer of one fascicle of ulnar nerve to the branch of the long head of the triceps is reliable for active elbow extension recovery in C5, C6 and C7 brachial plexus palsies.


Differential expression of several neurospecific beta-tubulin mRNAs in the mouse brain during development.
The expression of alpha- and beta-tubulin mRNAs has been studied during mouse brain development by using in vitro translation and specific cDNA clone hybridization techniques. The results presented here indicate that about half of the isotubulins expressed in vivo by brain cells are directly encoded by mRNA, the other isotypes being of post-translational origin. Among the six brain beta-tubulin mRNAs detected after RNA size fractionation followed by in vitro translation, four (1.8a, 1.8c, 2.4 and 3.5 kb) appear to be uniquely expressed in brain, and very likely in neurons. These four beta-tubulin RNA transcripts are differently regulated during development. The 1.8a-kb mRNA, which codes for the neurospecific beta' 1-isotubulin, is expressed very early, whereas the 1.8c, 2.4 and 3.5-kb mRNAs, which all code for a beta 4-tubulin isotype, are all expressed later. We isolated a beta-tubulin cDNA clone which specifically hybridizes to the large, neural 3.5-kb mRNA. The two other ubiquitous tubulin mRNAs, 1.8b and 2.9 kb in length, both direct the synthesis of an electrophoretically distinct beta 3 isotype. These results support the idea that within the tubulin multigene family, distinct beta-tubulin isogenes could be specifically expressed at various steps of the neuronal differentiation, thus contributing to the isotubulin diversity and specificity observed in this cell type and possibly involved in the developmental changes of its structure and function.


Effects of quercetin on aggregation and intracellular free calcium of platelets.
To study the effects of Que on the intraplatelet free calcium concentration and the effects of calcium on the inhibition of platelet aggregation by Que. Using Quin-2 fluorescence technique. Que inhibited the platelet aggregation and the rise of [Ca2+]i induced by thrombin in platelets. The values of IC50 and 95% confidence interval were 146.2 (92.4 - 231.3) and 78.5 (49.5 - 124.4) mumol.L-1, respectively. The inhibitory effects of Que on platelet aggregation induced by thrombin were reduced by adding calcium to the medium, and Que had no effect on thrombin-induced internal Ca2+ release from dense tubular system. The inhibitory effects of Que on aggregation and the rise of [Ca2+]i in platelets was mainly due to an inhibition of Ca2+ influx.


Spatial distribution of ectomycorrhizal Basidiomycete Russula subsect. Foetentinae populations in a primary dipterocarp rainforest.
The spatial distribution of basidiocarps of the ectomycorrhizal Basidiomycete Russula subsect. Foetentinae was assessed in a primary forest in the Western Ghâts (India) dominated by the ectomycorrhizal tree species Vateria indica and Dipterocarpus indicus. Over a 7,700-m(2) sampling area, both trees and basidiocarps of Russula subsect. Foetentinae were mapped during the first month of the 2002 rainy season. First-order spatial analysis revealed that the distribution of the 45 collected carpophores was highly aggregated, with 60% of all basidiocarps located at a distance lower than 1 m from the nearest one. The genetic structure of the Russula subsect. Foetentinae population was studied by inter-simple sequence repeat polymorphism analysis using three primers. Eighteen of the 45 genotypes were represented by single basidiocarps. Twenty-seven basidiocarps were identified as belonging to 11 genets or separated ramets. Five genets were small, with diameters ranging from 0.5 to 5 m. The six others were large, with a diameter ranging from 31 m to a maximum measured distance of 70 m. In spite of the lack of data concerning the reproductive biology of this species, the presence of large genets suggests that mature stands may shelter well-spread underground mycelium, crucial for durable interaction with plant partner.


Relative blood volume changes during haemodialysis estimated from haemoconcentration markers.
Relative blood volume (RBV) monitoring is frequently used in haemodialysis patients to help guide fluid management and improve cardiovascular stability. RBV changes are typically estimated based on online measurements of certain haemoconcentration markers, such as haematocrit (HCT), haemoglobin (HGB) or total blood protein concentration (TBP). The beginning of a haemodialysis procedure, i.e. filling the extracorporeal circuit with the patient's blood (with the priming saline being infused to the patient or discarded) may be associated with relatively dynamic changes in the circulation, and hence the observed RBV changes may depend on the exact moment of starting the measurements. The aim of this study was to use a mathematical model to assess this issue quantitatively. The model-based simulations indicate that when the priming saline is not discarded but infused to the patient, a few-minute difference in the moment of starting RBV tracking through measurements of HCT, HGB or TBP may substantially affect the RBV changes observed throughout the dialysis session, especially with large priming volumes. A possible overestimation of the actual RBV changes is the highest when the measurements are started within a couple of minutes after the infusion of priming saline is completed.


"Cannula-in-cannula" technique for turbulence control and suture management in arthroscopic superior capsular reconstruction-A technical note.
Arthroscopic superior capsular reconstruction is gaining popularity in managing irreparable rotator cuff tears in younger patients without arthrosis. One of many reasons for the increase in this trend is the simplification of technique using allograft and knotless technology for fixation. Despite all this, turbulence control and suture management are still arduous undertakings. In order to improve visualization and prevent entanglement of sutures, we employed the cannula-in-cannula technique which allowed a continuous fluid management and tangle-free handling of sutures.


Observational case series on adalimumab-induced paradoxical hidradenitis suppurativa.
Although the efficacy of TNF blockers has been demonstrated in hidradenitis suppurativa (HS), many paradoxical effects have also been described with TNF antagonists. We wished to describe patients with adalimumab (ADA)-induced paradoxical HS. This is a retrospective descriptive case series of four patients with ADA-induced paradoxical HS. All the patients had a good response to TNFa antagonist therapy at the time of HS occurrence. The time from TNFa antagonist initiation to HS onset or exacerbation ranged from a few weeks to 24 months. The outcome of HS was variable. Systemic antibiotics were required in all the cases to control HS. TNF blockers were continued in three cases with a switch to another anti-TNF class in one case. Switch to ustekinumab was prescribed in one patient with SA and Crohn's disease. Although the imputability of TNF blockers in paradoxical HS is still debatable, further research and observation are needed to confirm and distinguish patients with genetic and clinical predisposition in the onset or exacerbation of HS during anti-TNF treatment.


Trauma, narcissism and the two attractors in trauma.
In this paper, the author sets out to distinguish anew between two concepts that have become sorely entangled--'trauma' and 'narcissism'. Defining 'narcissism' in terms of an interaction between the selfobject and the self that maintains a protective shield, and 'trauma' as attacks on this protective shield, perpetrated by bad objects, he introduces two attractors present in trauma--'the hole attractor' and the structure enveloping it, 'the narcissistic envelope'. The hole attractor pulls the trauma patient, like a 'black hole', into a realm of emotional void, of hole object transference, devoid of memories and where often in an analyst's countertransference there are no reverberations of the trauma patient's experience. In the narcissistic envelope, on the other hand, motion, the life and death drive and fragments of memory do survive. Based on the author's own clinical experience with Holocaust survivors, and on secondary sources, the paper concludes with some clinical implications that take the two attractors into account.


Prizidilol in essential hypertension: long-term effects on plasma volume, extracellular fluid volume, and central hemodynamics at rest and during exercise.
We studied the long-term hemodynamic effect of prizidilol (a precapillary vasodilator and beta-adrenoceptor blocker) in 14 men aged 25-66 years with mild and moderate essential hypertension (EH). Cardiac output (by Cardiogreen) and intraarterial blood pressure (BP) were measured at rest and during exercise before and after 8 months of therapy. Changes in body fluid volumes were measured by isotope dilution techniques. After 8 months on prizidilol, eight of the 14 patients were normotensive, and the mean casual BP was lowered by 23/17 mm Hg to 140/91 mm Hg. The intraarterial systolic and diastolic pressures fell by 15-20% of the pretreatment levels at rest supine, sitting, and during 50, 100 and 150 W exercise. The fall in BP was due to a marked reduction in total peripheral resistance ranging from 17 to 23% at rest and during exercise. Cardiac output was unchanged at all work loads, whereas heart rate fell. The stroke volume increased in all settings; at maximum work load by 30%. Body weight and body fluid volumes did not change significantly. Except for some coldness in hands and feet in one patient, which disappeared after 2-3 months, no side effects were observed. We conclude that, in mild and moderate EH, prizidilol induces a substantial fall in BP with an excellent hemodynamic profile both at rest and during exercise.


Complexation of oppositely charged polyelectrolytes and surfactants in aqueous solutions. A review.
Addition of surfactants to aqueous solutions of polyelectrolytes causes the spontaneous formation of complexes in a certain range of concentrations. In some conditions, compact monodisperse multichain complexes are obtained (short surfactant chain length and polymer rigid enough). The size of the complexes can be varied in controlled way from nanometers up to micrometers, but depends on the mixing procedure, whereas the shape of the complexes depends on the polymer backbone rigidity. These complexes exhibit microstructures analogue to that of the precipitates formed at higher concentrations. In most cases, however, the complexes are large, soft and polydisperse.


Minimally invasive repair of pectus carinatum by the Abramson method: A systematic review.
The aim of this review is to provide an overview of the outcomes after minimally invasive pectus cartinatum repair (MIRPC) by the Abramson method to determine its effectiveness. The PubMed and Embase databases were systematically searched. Data concerning subjective postoperative esthetic outcomes after initial surgery and bar removal were extracted. In addition, data on recurrence, complications, operative times, blood loss, post-operative pain, length of hospital stay, planned time to bar removal and reasons for early bar removal were extracted. The postoperative esthetic result, was selected as primary outcome since the primary indication for repair in pectus carinatum is of cosmetic nature. Six cohort studies were included based on eligibility criteria, enrolling a total of 396 patients. Qualitative synthesis showed excellent to satisfactory esthetic results in nearly all patients after correctional bar placement (99.5%, n = 183/184). A high satisfaction rate of 91.0% (n = 190/209) was found in patients after bar removal. Recurrence rates were low with an incidence of 3.0% (n = 5/168). The cumulative postoperative complication rate was 26.5% (n = 105/396), of whom 25% required surgical re-intervention. There were no cases of mortality. Minimally invasive repair of pectus carinatum through the Abramson method is effective and safe. Its efficacy is demonstrated by the excellent to satisfactory esthetic results in 99.5% and 91.0% of patients after respectively correctional bar placement and implant removal. Future studies should aim to compare different treatment options for pectus carinatum in order to elucidate the approach of choice for different patient groups.


Hand dermatitis in auto mechanics and machinists.
Auto mechanics and machinists presenting with suspected allergic contact dermatitis (ACD) have traditionally been patch-tested with a standard screening tray and a specialty tray such as the Oil and Cooling Fluid Series. While this has proven useful for patch-testing the machinist, there is a need for the development of a more specific allergen testing tray for the auto mechanic. The objective of the study was to compare clinical features and patch-test results of auto mechanics and machinists with hand dermatitis to evaluate differences in allergen profiles. We performed a chart review of 33 auto mechanics and 24 machinists referred to our Occupational Contact Dermatitis Clinic from 2002 to 2005 for evaluation of hand dermatitis. With a panel of 84 allergens, 52 positive reactions were detected in 17 cases of ACD in mechanics. The profiles were different from the cases of ACD diagnosed in 10 of 24 machinists. Mechanics and machinists differ in the spectrum of occupational exposures. Patch testing with greater numbers of allergens likely identifies a larger proportion of mechanics with occupationally relevant ACD. Further study is needed to determine the most appropriate allergens to include in a clinically useful "mechanic's tray."


Drug-drug interactions in pediatric psychopharmacology.
Serious consequences caused by drug-drug interactions continue to plague contemporary pharmacotherapy. The possibility of a drug-drug interaction should be suspected anytime a new or unexpected effect occurs that complicates the clinical management of a patient in the setting where the patient is receiving more than one drug. In this article, the authors address the mechanisms of pharmacokinetic-based drug-drug interactions focusing on important interactions that may occur with the common medications a pediatrician may prescribe to the child receiving psychoactive medication(s) prescribed by a child psychiatrist.


Intestinal obstruction in a neonate with adrenal hemorrhage and renal vein thrombosis.
Adrenal hemorrhage and renal vein thrombosis are two distinct vascular entities encountered in the newborn period. Occasionally, both entities may co-exist in the same patient. A premature infant of a diabetic mother presented with intestinal obstruction secondary to extrinsic compression by the mass effect of the enlarged hemorrhagic adrenal and thrombosed kidney on the left hemicolon, a phenomenon which to our knowledge has not previously been described.


Plastic mulch film induced soil microplastic enrichment and its impact on wind-blown sand and dust.
Microplastics (MPs) pollution is being increasingly recognized as a global concern in all environments. Wind-blown sand and dust contaminated by MPs are an important pathway of MPs transport across different environments, which can result in on-site and off-site potential MP pollution. Here, we designed field experiments to detect MPs in surface soil and wind-blown sand and dust in farmlands with and without film mulch in a semi-arid region of northern China. This study provides the first insights into MPs enrichment in wind-blown sand and dust deposited by natural storms. The results reveal that fibers, fragments, and films constitute the major types of MPs in farmland soil and wind-blown sand and dust. The MPs abundances of 1-3 mm, <1 mm, and 3-5 mm items kg-1 successively decrease. The enrichment of MPs in wind-blown dust is one to two orders of magnitude higher than that in wind-blown sand. For the farmlands with (without) film mulch, the MPs enrichment ratios ranged from 0.22 (0.29) to 1.35 (2.26) in the wind-blown sand and that varied from 1.79 (1.01) to 16.6 (25.79) in the wind-blown dust. Fibers are preferentially transported by wind erosion compared to fragments and films. Soil aggregating processes, wind speed, and MPs shape may influence enrichment in wind-blown sand and dust. Film mulch debris and the application of manure may be the primary sources of MPs in farmland soils. This study further highlights the importance of the transport of airborne MPs from surface soil into the atmosphere. Future research is required to establish the quantitative relationships between the MPs shape, wind speed, and surface soil properties and the MPs enrichment in wind-blown sand and dust.


Mannosylglycerate is essential for osmotic adjustment in Thermus thermophilus strains HB27 and RQ-1.
We disrupted the mpgS encoding mannosyl-3-phosphoglycerate synthase (MpgS) of Thermus thermophilus strains HB27 and RQ-1, by homologous recombination, to assess the role of the compatible solute mannosylglycerate (MG) in osmoadaptation of the mutants, to examine their ability to grow in NaCl-containing medium and to identify the intracellular organic solutes. Strain HB27 accumulated only MG when grown in defined medium containing 2% NaCl; mutant HB27M9 did not grow in the same medium containing more than 1% NaCl. When trehalose or MG was added, the mutant was able to grow up to 2% of NaCl and accumulated trehalose or MG, respectively, plus amino acids. T. thermophilus RQ-1 grew in medium containing up to 5% NaCl, accumulated trehalose and lower amounts of MG. Mutant RQ-1M1 lost the ability to grow in medium containing more than 3% NaCl and accumulated trehalose and moderate levels of amino acids. Exogenous MG did not improve the ability of the organism to grow above 3% NaCl, but caused a decrease in the levels of amino acids. Our results show that MG serves as a compatible solute primarily during osmoadaptation at low levels of NaCl while trehalose is primarily involved in osmoadaptation during growth at higher NaCl levels.


The epidemiology of clinically apparent HIV infection in Nicaragua.
The purpose of this study was to describe the epidemic of clinically apparent human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) infection in Nicaragua and to discuss the reasons why the number of HIV patients presenting to the public health care system is increasing compared with other Central American countries. From 1987 to 2004, 1,614 HIV-positive patients were officially reported to the Nicaraguan STI/HIV/AIDS national program. Urban areas along the west-central and eastern part of Nicaragua showed the highest prevalence of AIDS, with a maximum of 54.2/year per 100,000 inhabitants. Most of the infections (91%) were acquired sexually: 65% by heterosexual contacts and 26% by homosexual contacts. The highest rate of infection was found in men aged between 20 to 39 years, with a peak around 35 to 39 years (annual incidence of 125.6 new cases per 100,000 inhabitants), and in women aged 20 to 34 years old, with a peak around 20 to 24 years (annual incidence 46.6 per 100,000 inhabitants). The male to female ratio of infection was 3:1. The death rate was stable until the beginning of 1999, but increased sharply thereafter up to 2004, the year that highly active antiretroviral therapy (HAART) was introduced in Nicaragua. In 2005, we observed a further increase in the mortality. However, our data do not represent the magnitude of the HIV/AIDS epidemic as a whole, due to a lack of systemic surveillance. HIV/AIDS in Nicaragua is in a nascent stage and is concentrated in high-risk populations, such as utility workers, commercial sex workers, men who have sex with men, prisoners, street children, housewives and police and military forces. Education of the population is an urgent need to increase HIV/AIDS-related knowledge, change attitudes, and increase safer sex practice in the community.


From Qualitative to Quantitative Analysis of Activity and Property Landscapes.
Activity or, more generally, property landscapes (PLs) have been considered as an attractive way to visualize and explore structure-property relationships (SPRs) contained in large data sets of chemical compounds. For graphical analysis, three-dimensional representations reminiscent of natural landscapes are particularly intuitive. So far, the use of such landscape models has essentially been confined to qualitative assessment. We describe recent efforts to analyze PLs in a more quantitative manner, which make it possible to calculate topographical similarity values for comparison of landscape models as a measure of relative SPR information content.


Analysis of the argK-tox gene cluster in nontoxigenic strains of Pseudomonas syringae pv. phaseolicola.
The analysis of 46 isolates obtained directly from different and distant common bean fields from the northwestern part of Spain revealed that they do not produce phaseolotoxin. The isolates were classified as race 5, and their analysis revealed that they do not carry the argK-tox gene cluster involved in the biosynthesis of the phaseolotoxin.


Handling, task complexity, time-of-day, and sleep deprivation as dynamic modulators of recognition memory in mice.
Sleep is essential for optimal cognitive functioning. Although we lack a complete understanding of the role of sleep in memory consolidation, we know that various factors that disturb sleep or sleep quality have consequences for cognitive performance. Such factors can be unintended components of behavioral experiments on rodents and other experimental animals that generate differing results from different labs. These experimental variables include habituation to handling, intended or unintended sleep deprivation, task complexity, time of testing, and environmental features. We have examined how these variables impact recognition memory in C57BL/6 mice. Handled mice outperformed their non-handled counterparts across different combinations of delay phase duration and lighting conditions. Results also suggest that simple task recall is more resistant to diurnal variation and the impairing effects of sleep deprivation than is complex task recall. This study underscores the role of protocol and environmental factors in recognition memory and in conflicting results from different laboratories.


A dual role for caveolin-1 in the regulation of fibronectin matrix assembly by uPAR.
The relationship between the plasminogen activator system and integrin function is well documented but incompletely understood. The mechanism of uPAR-mediated signaling across the membrane and the molecular basis of uPAR-dependent activation of integrins remain important issues. The present study was undertaken to identify the molecular intermediates involved in the uPAR signaling pathway controlling alpha5beta1-integrin activation and fibronectin polymerization. Disruption of lipid rafts with MbetaCD or depletion of caveolin-1 by siRNA led to the inhibition of uPAR-dependent integrin activation and stimulation of fibronectin polymerization in human dermal fibroblasts. The data indicate a dual role for caveolin-1 in the uPAR signaling pathway, leading to integrin activation. Caveolin-1 functions initially as a membrane adaptor or scaffold to mediate uPAR-dependent activation of Src and EGFR. Subsequently, in its phosphorylated form, caveolin-1 acts as an accessory molecule to direct trafficking of activated EGFR to focal adhesions. These studies provide a novel paradigm for the regulation of crosstalk among integrins, growth-factor receptors and uPAR.


Effect of timing of cerebral ultrasonography on the prediction of later neurodevelopmental outcome in high-risk preterm infants.
To determine the predictive value of cranial ultrasonographic examination in high-risk preterm infants at different postnatal ages, we scanned 110 infants less than or equal to 32 weeks gestational age at 1, 2, 3, and 6 weeks postnatal ages and at 40 weeks postconceptional age (PCA). Cranial abnormalities detected by ultrasonography at each postnatal age of examination were classified as minor (periventricular superolateral echogenicity with or without intraventricular hemorrhage, grades 1 to 3) or major (cystic periventricular leukomalacia with or without intraventricular hemorrhage, grade 4) and correlated with neurodevelopmental outcome determined by 1 year of age. Major abnormalities detected by ultrasonography were present in four infants at 1 week, four at 2 weeks, eight at 3 weeks, and 11 infants at 6 weeks and 40 weeks PCA, respectively. Nineteen infants (17%) had moderate to severe functional handicaps defined as cerebral palsy, cognitive or visual deficit, or deafness. The positive and negative predictive values of ultrasound examinations, with regard to later neurodevelopmental outcome, improved with increasing postnatal age at examination and was best at 40 weeks PCA. Negative results of ultrasound study at 40 weeks PCA most correctly predicted satisfactory outcome. Although only 58% of moderately to severely handicapped infants were correctly identified by ultrasound examination at 40 weeks PCA, all infants with major ultrasonographic abnormalities at 40 weeks PCA had moderate or severe handicap. Our data demonstrate that the timing of cerebral ultrasonography is important in the prediction of later neurodevelopmental outcome in high-risk preterm infants.


Pilot trial of the effects of low-dose acetylsalicylic acid on platelet thromboxane B2 production.
It has been suggested that certain foods of plant origin contain milligram-quantities of acetylsalicylate which could exert an anti-thrombotic effect. Acetylsalicylic acid prevents cardiovascular diseases through inhibition of platelet endoperoxide thromboxane production and platelet aggregation. We investigated whether a daily intake of 3 mg acetylsalicylic acid causes a measurable decrease of platelet cyclo-oxygenase activity assessed by in vitro thromboxane B2 production. We carried out a randomised, double-blind, placebo-controlled cross-over study. Ten healthy volunteers (5 men, 5 women) aged 22 +/- 3 years (mean +/- s.d) participated in the study; there were no drop-outs. Participants took 3 mg/d of acetylsalicylic acid or a placebo for 2 weeks each. At the end of each treatment period venous blood was drawn, and platelet-rich plasma was stimulated with arachidonic acid. Treatment with acetylsalicylic acid caused a 39 +/- 8% decrease in maximal thromboxane B2 production (P = 0.000), which was independent of treatment order. Quantitative data on acetylsalicylate in foods and the possible antithrombotic action of a diet rich in acetylsalicylate deserve closer investigation.


Life extension by dietary restriction in the bowl and doily spider, Frontinella pyramitela.
Longevity of free-living female adult bowl and doily spiders was compared with that of captive spiders fed at dietary regimes of one, three, and five Drosophila melanogaster per week. Adult females lived, on average, only 8 days in the field and the pattern of survivorship showed no evidence that senescence contributed to mortality. In the laboratory, mean adult life span was 81.3, 63.9, and 42.3 days on the one, three, and five Drosophila diets, respectively. Decreased feeding rate also delayed egg laying and reduced total fecundity. Survival and reproductive patterns indicated the manifestation of spider senescence at all laboratory feeding levels, with a younger onset of senescence at the higher feeding rates.