Human and Animal Fascioliasis in Iran: Systematic Review and Meta-analysis.
The aim of this study was to investigate the prevalence of fascioliasis in humans, cattle, sheep, and goats, done by a systematic review in Iran. Fifty articles were extracted including Iranian papers such as Google scholar, Magiran, Iran Medex, SID, and Pubmed. Out of these, 21 articles were selected for meta-analysis. Essential information for meta-analysis was extracted from papers and archived in Excel software for calculating by statistical analysis. The variance of each study was obtained using the binomial distribution. Heterogeneity of the studies was surveyed using I2 index. Data were analyzed using a random effect model. Of 21 collected papers, 1,275,506 samples from cow (507,152), sheep (454,882), goat (207,925), and human (105,547) had been surveyed in Iran. Eight studies were conducted on humans and 13 on animals. The prevalence rate obtained in humans was 3% with a confidence interval (CI) of 95% (1%-7%). Prevalence rate obtained in cows, sheep, and goats was 13% with CI of 95% (10%-16%). The highest level of prevalence was reported from cities in the North in animals with a prevalence of 14%. The highest level of prevalence was reported from Gilan in humans with a prevalence of 0.1%. The prevalence of the Fascioliasis in Iran has reduced in recent years, But the importance of the disease has not reduced and there is a possibility of an epidemic. Furthermore, in many cities of Iran, there is no study on the disease.


Permeability of Pseudomonas aeruginosa outer membrane to hydrophilic solutes.
Pseudomonas aeruginosa is usually resistant to a wide variety of antibacterial agents, and it has been inferred, on the basis of indirect evidence, that this was due to the low permeability of its outer membrane. We determined the permeability of P. aeruginosa outer membrane directly, by measuring the rates of hydrolysis of cephacetrile, cephaloridine, and various phosphate esters by hydrolytic enzymes located in the periplasm. The permeability to these compounds was about 100-fold lower than in the outer membrane of Escherichia coli K-12. Also, we found that the apparent Km values for active transport of various carbon and energy source compounds were typically higher than 20 microM in P. aeruginosa, in contrast to E. coli in which the values are usually lower than 5 microM. These results also are consistent with the notion that the P. aeruginosa outer membrane indeed has a low permeability to most hydrophilic compounds and that this membrane acts as a rate limiting step in active transport processes with high Vmax values.


Voltage-controlled slow light in an integrated semiconductor structure with net gain.
We demonstrate the use of coherent population oscillations (CPO) to realize a monolithically integrated semiconductor device which allows voltage controlled tuning of the group velocity corresponding to a phase shift of up to 55 degrees at a frequency of 10 GHz. By combining sections of slow and fast light, corresponding to absorption and gain, we demonstrate control of both the slow-down factor and the signal amplitude, which is important for applications as true-time delay in microwave photonics. The physics of CPO is discussed in relation to electromagnetically induced transparency (EIT). In particular, we demonstrate and explain the possibility of achieving transparency when using the effect of CPO despite the fact that it relies on only a partial saturation of an absorption line.


Molecular mechanisms that control leukocyte extravasation: the selectins and the chemokines.
Attachment of leukocytes to the blood vessel wall initiates leukocyte extravasation. This enables leukocytes to migrate to and accumulate at sites of tissue injury or infection where they execute host-defense mechanisms. A series of vascular cell adhesion molecules on leukocytes and on endothelial cells mediate leukocyte attachment to the endothelium in a stepwise process. A large panel of about 40 known human chemokines is able to specifically activate certain leukocytes and attract them to migrate across the endothelial barrier and within tissue. The specific combination of molecular signals provided by the diversity of cytokines, adhesion molecules, and chemokines regulates the specificity and selectivity of the recruitment of certain subpopulations of leukocytes in vivo. This review will focus on selectins and chemokines which initiate the cell contact and regulate activation and chemoattraction of leukocytes.


Analysis of canine herpesvirus gB, gC and gD expressed by a recombinant vaccinia virus.
The genes encoding the canine herpesvirus (CHV) glycoprotein B (gB), gC and gD homologues have been reported already. However, products of these genes have not been identified yet. Previously, we have identified three CHV glycoproteins, gp 145/112, gp80 and gp47 using a panel of monoclonal antibodies (MAbs). To determine which CHV glycoprotein corresponds to gB, gC or gD, the putative genes of gB, gC, and gD of CHV were inserted into the thymidine kinase gene of vaccinia virus LC16mO strain under the control of the early-late promoter for the vaccinia virus 7.5-kilodalton polypeptide. We demonstrated here that gp145/112, gp80 and gp47 were the translation products of the CHV gB, gC and gD genes, respectively. The antigenic authenticity of recombinant gB, gC and gD were confirmed by a panel of MAbs specific for each glycoprotein produced in CHV-infected cells. Immunization of mice with these recombinants produced high titers of neutralizing antibodies against CHV. These results suggest that recombinant vaccinia viruses expressing CHV gB, gC and gD may be useful to develop a vaccine to control CHV infection.


Economic outcomes of eszopiclone treatment in insomnia and comorbid major depressive disorder.
Eszopiclone is effective for the treatment of insomnia in patients with insomnia and comorbid major depressive disorder (MDD). Both conditions impose significant economic burden, with the US societal cost of depression estimated at USD 50 billion annually. The purpose of this analysis was to examine the costs and benefits of eszopiclone co-administered with fluoxetine (ESZ+FLX) compared to placebo co-administered with fluoxetine (PBO+FLX) in adults meeting the DSM-IV criteria for insomnia and MDD. Data from 434 patients enrolled in an 8-week clinical trial who met the economic-subanalysis criteria were examined. The costs of medical care (in 2007 USUSD ) and lost work time were estimated from the Hamilton Depression Scale (HAM-D17) scores using published algorithms. Cost of lost productivity while at work was based on responses to the Work Limitations Questionnaire. The impact of therapy on quality-adjusted life years (QALYs) was estimated by transforming HAM-D17 (base case analysis) or Short Form Health Survey (SF-12) (scenario analyses) responses into health utility scores using published algorithms. Drug costs were estimated based on average wholesale price. The mean 8-week increases in QALYs from baseline were 0.0392 and 0.0334 for the ESZ+FLX and PBO+FLX groups, respectively. Mean per-patient costs were USD 1,279 and USD 1,198 for the respective groups. Thus, co-treatment resulted in net increases of 0.0058 QALYs and USD 81, leading to an incremental cost per QALY gained of approximately USD 14,000. Co-administration of eszopiclone and fluoxetine improved patients' insomnia symptoms and appeared to be a cost-effective treatment strategy for patients with insomnia and comorbid MDD. One limitation of this study is that optimal utility estimation techniques were not available. Utilities were instead derived indirectly using the HAM-D17 (disease-specific, not generic) or SF-12 (generic, but potentially insensitive to important changes in some conditions) instruments. Sleep disturbance is predictive of depression relapse, and is the most common residual symptom in patients who have been successfully treated with fluoxetine for depression. Thus, identifying cost-effective strategies for the treatment of insomnia symptoms is important for this patient population. Treatment guidelines and drug coverage decisions should be based on clinical evidence, effectiveness, and economic criteria (i.e., whether an effective drug therapy produces sufficient benefits given its costs). This information about the overall value of eszopiclone can be measured as the cost per QALY gained with the use of ESZ+FLX compared with FLX alone. In order to make decisions based on value, payers and policy makers must have access to reliable cost-effectiveness information. The residual efficacy observed in the clinical trial following the discontinuation of co-therapy should be explored further to determine whether intermittent treatment with ESZ+FLX is a cost-effective strategy.


Exploring health facilities' experiences in implementing the free health-care policy (FHCP) in Nepal: how did organizational factors influence the implementation of the user-fee abolition policy?
This article presents an Asian experience of abolishing health-care user fees: Nepal's universal free health-care policy, implemented in 2008. Based on doctoral fieldwork between August 2008 and April 2009, the paper analyses primary-care facilities' and central and district health systems' experiences with the policy. It makes a unique contribution to existing evidence because it explicitly applies organizational theory within a carefully designed, rigorous, multiple case-study analysis to deepen our understanding of the organizational and 'people' factors in the successful removal of user fees. The cases were two pairs of primary-care facilities in one district, paired for comparison of the facilities' experiences with the policy in relation to its effects on health care utilization. Data collection methods included document reviews; key informant interviews at district and central levels; in-depth, semi-structured interviews and group interviews at case facilities. (Data on indicators of utilization and quality changes over time were also collected and will be published separately). Using key elements of Nadler and Tushman's 'Organizational Congruence' model, a degree-of-fit analysis tested the study's initial propositions and yielded generalizations for contexts in and outside Nepal. The study found that Nepal's key implementation challenges were similar to Africa's: insufficient or delayed inputs of drugs and compensation; insufficient workforce and the resulting reduced quality of services that hampered facilities' relationships with their clients and health providers' attitudes. However, the Nepalese case facilities with (1) good intra- and inter-facility relationships, (2) adequate staffing, (3) well-oriented providers and (4) previously trained, better-informed and skilled health management committees experienced higher utilization and better-quality indicators over time. Through its detailed analysis of Nepal's experience in removing user fees, the study highlights the importance of addressing the 'people' and 'organizational' factors in health-policy development and implementation.


Modeling and control for closed environment plant production systems.
A computer program was developed to study multiple crop production and control in controlled environment plant production systems. The program simulates crop growth and development under nominal and off-nominal environments. Time-series crop models for wheat (Triticum aestivum), soybean (Glycine max), and white potato (Solanum tuberosum) are integrated with a model-based predictive controller. The controller evaluates and compensates for effects of environmental disturbances on crop production scheduling. The crop models consist of a set of nonlinear polynomial equations, six for each crop, developed using multivariate polynomial regression (MPR). Simulated data from DSSAT crop models, previously modified for crop production in controlled environments with hydroponics under elevated atmospheric carbon dioxide concentration, were used for the MPR fitting. The model-based predictive controller adjusts light intensity, air temperature, and carbon dioxide concentration set points in response to environmental perturbations. Control signals are determined from minimization of a cost function, which is based on the weighted control effort and squared-error between the system response and desired reference signal.


Polycystic Ovary Syndrome as a systemic disease with multiple molecular pathways: a narrative review.
Polycystic Ovary Syndrome (PCOS) is characterized by hyperandrogenism, amenorrhea, and polycystic ovaries. This endocrinopathy is associated with many metabolic disorders such as dyslipidemia and insulin resistance, with increased risk of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular complications. Inflammation is likely to play an important role in the promoting these metabolic imbalances, while prothrombotic and pro-oxidative mechanisms further contribute to the cardiovascular risk of these patients. The etiology of PCOS is still not fully understood, but there is evidence of genetic and environmental components. This review aims to discuss some molecular pathways associated with PCOS that could contribute to the better understanding about this syndrome. Recent evidence suggests that intrauterine exposure of female mice to an excess of anti-Müllerian hormone may induce PCOS features in their post-natal life. High cytokine levels and cytokine gene polymorphisms also appear to be associated with the pathophysiology of PCOS. Furthermore, high levels of microparticles may contribute to the altered hemostasis and enhanced inflammation in PCOS. All these mechanisms may be relevant to clarify some aspects of PCOS pathogenesis and inspire new strategies to prevent the syndrome as well as treat its symptoms and mitigate the risk of long-term complications.


Screening of gastric cancer: who, when, and how.
Gastric cancer (GC) remains the leading cause of cancer mortality worldwide. Conceivably, early diagnosis may be achievable through screening of the high-risk population. Therefore, it is important to identify individuals harboring premalignant lesions that include atrophic gastritis, intestinal metaplasia, and mucosal dysplasia. The age threshold for GC screening depends on the regional incidence and the individual risk. In high-incidence countries such as Japan and Korea, the age to screen GC may be as early as 40 years. The mass screening by endoscopy in these countries would be able to detect a substantial portion of patients with early GCs as well as precancerous lesions. For the purpose of eliminating GC, however, these screening programs should be conducted in conjunction with Helicobacter pylori eradication. In low-incidence countries, it seems feasible to adopt a stepwise approach to identify high-risk individuals at first. The initial screening should focus on epidemiologic factors, genetic or hereditary risks, and the status of H pylori infection. Measurement of serum pepsinogen I and II and gastrin may detect atrophic gastritis in a noninvasive manner. Patients with these premalignant lesions should then receive endoscopic examination and enter surveillance. To date, there is no cost-effective strategy for an average-risk individual from a population with low incidence of GC, and therefore screening is unwarranted and cannot be recommended for them.


The impact of friends on young adults' drinking over the course of the evening--an event-level analysis.
To examine whether young adults' alcohol consumption during the course of an evening was affected by the number of friends present, and the interaction between participants' gender and number of friends present. Participants used the internet-based cellphone-optimized assessment technique (ICAT) to complete a series of cellphone questionnaires every Thursday, Friday and Saturday evening over five weekends. A multi-level growth curve model (hourly assessments, clustered within evenings, clustered within individuals) with time-invariant and time-varying covariates was estimated. French-speaking Switzerland. A total of 183 young adults (53.0% female, mean age = 23.1) who completed 7205 questionnaires on 1441 evenings. Alcohol consumption and number of friends present assessed at 8 p.m., 9 p.m., 10 p.m., 11 p.m. and midnight. Drinking pace accelerated notably over the course of the evening on Saturdays (b = 0.047; P < 0.01). Men consumed more alcohol than women, particularly at the beginning of the evening (b = 0.152; P < 0.05). However, this effect was no longer significant when the impact of friends was accounted for (b = 0.096; P = 0.139). The higher the number of friends present, the higher the number of drinks consumed at a given time during the course of the evening (b = 0.070; P < 0.001). Cross-level interaction effects indicated that this relationship was stronger for men than women (b = 0.027; P < 0.05). Among young adults in Switzerland, the number of friends present is associated positively with hourly drinking frequency during the course of weekend evenings. The impact of the drinking group size on alcohol use is stronger for men than women.


Gains in fluid intelligence after training non-verbal reasoning in 4-year-old children: a controlled, randomized study.
Fluid intelligence (Gf) predicts performance on a wide range of cognitive activities, and children with impaired Gf often experience academic difficulties. Previous attempts to improve Gf have been hampered by poor control conditions and single outcome measures. It is thus still an open question whether Gf can be improved by training. This study included 4-year-old children (N = 101) who performed computerized training (15 min/day for 25 days) of either non-verbal reasoning, working memory, a combination of both, or a placebo version of the combined training. Compared to the placebo group, the non-verbal reasoning training group improved significantly on Gf when analysed as a latent variable of several reasoning tasks. Smaller gains on problem solving tests were seen in the combination training group. The group training working memory improved on measures of working memory, but not on problem solving tests. This study shows that it is possible to improve Gf with training, which could have implications for early interventions in children.


[What surgical treatment for femoro-acetabular impingement?]
Femoroacetabular impingement (FAI) is a frequent cause of hip pain in young people and athletes. It requires a complete work-up, including X-rays, hip arthro-MRI and CT coxometry with measurement of femoral torsion. The surgical management of CFA must be adapted to the morphological anomalies of the femur (cam), acetabulum (pincer) and femoral torsional disorders. Most CFA can be treated by hip arthroscopy, with correction of the cam and suture of the labrum. Some CFA with a bulky or posterior cam require surgical hip dislocation. A femoral rotation or derotation osteotomy can correct an associated torsional disorder. In cases of marked retroversion of the acetabulum, anteverting periacetabular osteotomy can reorient the acetabulum.


Disaster behavioral health capacity: Findings from a multistate preparedness assessment.
To identify gaps in disaster behavioral health, the Preparedness and Emergency Response Learning Center (PERL) at the University of Minnesota's School of Public Health supported the development and implementation of a multistate disaster behavioral health preparedness assessment. Information was gathered regarding worker knowledge of current disaster behavioral health capacity at the state and local level, and perceived disaster behavioral health training needs and preferences. Between May and July 2015, 143 participants completed a 31-item uniform questionnaire over the telephone by a trained interviewer. Trained interviewers were given uniform instructions on administering the questionnaire. Participants included county and city-level public health leaders and directors from Minnesota, Wisconsin, and North Dakota. Findings demonstrate that across the three states there is a need for improved disaster behavioral health training and response plans for before, during, and after public health emergencies. This study identified perceived gaps in plans and procedures for meeting the disaster behavioral health needs of different atrisk populations, including children, youth, and those with mental illness. There was consistent agreement among participants about the lack of behavioral health coordination between agencies during emergency events. Findings can be used to inform policy and the development of trainings for those involved in disaster behavioral health. Effectively attending to interagency coordination and mutual aid agreements, planning for effective response and care for vulnerable populations, and targeted training will contribute to a more successful public health response to emergency events.


[Do vitamins from foods fortified exceed the allowed limits? Study carried out in population young adolescent and young adult of the metropolitan region of Chile].
In order to analyze the usual consumption of vitamins in an adolescent population and young adult in the Metropolitan Region, were 213 food fortified with vitamins of the Chilean market. A survey of consumption and nutrient intake was calculated. The result added vitamins added to food. The normality of the variables of the intake was assessed and data were subjected to analysis of descriptive statisticians and percentiles are determined. Estimated percentages of subjects whose values exceed those fixed for DDR and UL listed for each vitamin and percentage of excess for each case. Discriminant analysis was performed using the M Box test. The correlation canonical and the Statisticians Wilks were estimated. Finally it was estimated the percentage of correctly classified data. Data were processed by the program SPSS 20.0 with a significance level of α ≤ 0.05. The results indicate that you for all the studied vitamins, the percentage of subjects who more than the DDR is for total folate (96.4%) and the lowest percentage is given for the vitamin E and B12 in young adult women. The percentage of subjects who exceed the UL values is greatest for the vitamin B3 (91.9%). According to the canonical correlation, there are differences in behavior between the groups. It is recommended to monitor the behavior and consumption of food fortified with vitamins, especially of the complex B and A.


Classification of RNA backbone conformations into rotamers using 13C' chemical shifts: exploring how far we can go.
The conformational space of the ribose-phosphate backbone is very complex as it is defined in terms of six torsional angles. To help delimit the RNA backbone conformational preferences, 46 rotamers have been defined in terms of these torsional angles. In the present work, we use the ribose experimental and theoretical 13C' chemical shifts data and machine learning methods to classify RNA backbone conformations into rotamers and families of rotamers. We show to what extent the experimental 13C' chemical shifts can be used to identify rotamers and discuss some problem with the theoretical computations of 13C' chemical shifts.


[The influence of afferent inputs from the foot load receptors onto spinal alpha-motoneurons excitability in air-stepping condition].
We investigated excitability of alpha-motoneurons during voluntary and passive locomotor-like movements under air-stepping conditions during the imitation of foot loading. Limb loading notably inhibited the H-reflex during both static condition and active or passive stepping. Thus, load-related afferent inputs play an essentially role in phase-dependence H-reflex modulation. The excitability of alpha-motoneurons in the most degree is influenced by afferent inflow from foot receptors.


Classes of medications prescribed to malnourished children and their relationship with time to recovery.
There is conflicting evidence around prescription practices in the management of malnutrition; the study objective was to explore medication classifications prescribed and their relationship between time-to-recovery and specific demographic characteristics among children with malnutrition in Guatemala. Descriptive correlational study of data obtained in a retrospective record review. Children aged 0-5 years with malnutrition treated in a Guatemalan Nutrition Rehabilitation Center between 2019 and 2020 (N = 155). Variables assessed were medication classification of prescribed medications, age, gender, time-to-recovery, malnutrition severity, and COVID cohort. The most frequently used medication classifications were vitamins (95%), respiratory (75%), antipyretic (68%), antibiotic (61%), and gastrointestinal agents (54%). Antibiotic, respiratory, corticosteroid, antipyretic, and gastrointestinal agents were prescribed significantly more in cases with a time-to-recovery of 6 weeks or greater. Medication classifications prescribed most often were related to common comorbidities of malnutrition and illnesses affecting children in Guatemala, such as respiratory and diarrheal diseases. The medication used in cases with a time-to-recovery of ≥6 weeks suggest these cases may have had more comorbidities, which could explain the longer recovery times. Caution is suggested in routine prophylactic antibiotic use in public health settings, given the lack of association with improved recovery times, the potential for antibiotic drug resistance, and the negative effects on renal function among children.


Integrating network pharmacology and experimental validation to explore the mechanisms of luteolin in alleviating fumonisin B1-induced intestinal inflammatory injury.
Contamination with fumonisin B1 (FB1) represents a global health problem. FB1 exposure may also trigger intestinal injury by activating inflammatory responses, leading to a reduction in production performance and economic benefits. However, the mechanism of FB1-induced intestinal inflammatory injury is still unclear. At the same time, it is urgent to develop antibiotic alternatives and therapeutic targets to alleviate antibiotic resistance and to ensure effective treatment of intestinal inflammatory injury. We combined network pharmacology and in vitro experiments to explore the core therapeutic targets and potential mechanism of luteolin in FB1-induced intestinal inflammatory injury. Network pharmacology and molecular docking revealed that nuclear factor kappa B (NF-κB) p65, extracellular signal-regulated kinase (ERK), interleukin 6 (IL-6) and IL-1β are the important targets, and the NF-κB and ERK signalling pathways are critical in FB1-induced intestinal inflammatory injury. Besides, in vitro experiments further demonstrated that luteolin can inhibit FB1-induced intestinal inflammatory injury by inhibiting activation of the NF-κB and ERK signalling pathways and reducing the expression of IL-6 and IL-1β in IPEC-J2 cells. We have comprehensively illustrated the potential targets and molecular mechanism by which luteolin can alleviate FB1-induced intestinal inflammatory injury. Luteolin may be an effective antibiotic alternative to prevent intestinal inflammatory injury.


A new treatment strategy for severe arthrofibrosis of the knee. Surgical technique.
To reduce the morbidity of traditional quadricepsplasty for the treatment of severe arthrofibrosis of the knee, we instituted a treatment regimen consisting of an initial extra-articular mini-invasive quadricepsplasty and subsequent intra-articular arthroscopic lysis of adhesions during the same anesthesia session. The purpose of the present study was to determine the results of this technique. From 1998 to 2001, twenty-two patients with severely arthrofibrotic knees were managed with this operative technique. The mean age of the patients at the time of the operation was thirty-seven years. After a mean duration of follow-up of forty-four months (minimum, twenty-four months), all patients were evaluated according to the criteria of Judet and The Hospital for Special Surgery knee-rating system. The average maximum degree of flexion increased from 27 degrees preoperatively to 115 degrees at the time of the most recent follow-up (p < 0.001). According to the criteria of Judet, the result was excellent for sixteen knees, good for five, and fair for one. The average Hospital for Special Surgery knee score improved from 74 points preoperatively to 94 points at the time of the most recent follow-up (p < 0.001). A superficial wound infection occurred in one patient. Only one patient had a persistent 15 degrees extension lag. This mini-invasive operation for the severely arthrofibrotic knee can be used to increase the range of motion and enhance functional outcome.


An in vivo study of glass ceramic (Dicor) inlays. Preliminary report.
For the purpose of evaluating the clinical quality of glass ceramic (Dicor) inlays 15 patients with 37 inlays were examined 1 to 22 months after placement. In addition to certain periodontal variables, the inlays were rated by two independent examiners using the California Dental Association (CDA) quality evaluation system. The results of the present study showed that dental plaque was seen less often on proximal surfaces with inlays than on homologous proximal surfaces. Three patients reported hypersensitivity of the dental pulp. The examination using the CDA criteria showed that 54% of the inlays had a slight color mismatch, and slightly roughened surfaces were occasionally seen (35.5%). In nearly 30% of the inlays there was visible evidence of ditching along the margins. At present, no judgement can be made about the longevity of ceramic inlays.


The diversity, evolution and ecology of Salmonella in venomous snakes.
Reptile-associated Salmonella bacteria are a major, but often neglected cause of both gastrointestinal and bloodstream infection in humans globally. The diversity of Salmonella enterica has not yet been determined in venomous snakes, however other ectothermic animals have been reported to carry a broad range of Salmonella bacteria. We investigated the prevalence and diversity of Salmonella in a collection of venomous snakes and non-venomous reptiles. We used a combination of selective enrichment techniques to establish a unique dataset of reptilian isolates to study Salmonella enterica species-level evolution and ecology and used whole-genome sequencing to investigate the relatedness of phylogenetic groups. We observed that 91% of venomous snakes carried Salmonella, and found that a diverse range of serovars (n = 58) were carried by reptiles. The Salmonella serovars belonged to four of the six Salmonella enterica subspecies: diarizonae, enterica, houtanae and salamae. Subspecies enterica isolates were distributed among two distinct phylogenetic clusters, previously described as clade A (52%) and clade B (48%). We identified metabolic differences between S. diarizonae, S. enterica clade A and clade B involving growth on lactose, tartaric acid, dulcitol, myo-inositol and allantoin. We present the first whole genome-based comparative study of the Salmonella bacteria that colonise venomous and non-venomous reptiles and shed new light on Salmonella evolution. Venomous snakes examined in this study carried a broad range of Salmonella, including serovars which have been associated with disease in humans such as S. Enteritidis. The findings raise the possibility that venomous snakes could be a reservoir for Salmonella serovars associated with human salmonellosis.


Physiology of transgenic mice with brown fat ablation: obesity is due to lowered body temperature.
We investigated the physiological basis for development of obesity in uncoupling protein-diphtheria toxin A chain (UCP-DTA) transgenic mice. In these mice the promoter of the brown adipose tissue (BAT)-specific UCP was used to drive expression of DTA, resulting in decreased BAT function and development of obesity and insulin resistance (Lowell, B. B., S. V. Susulic, A. Hamann, J. A. Lawitts, J. Himms-Hagen, B. B. Boyer, L. Kozak, and J. S. Flier. Nature 366: 740-742, 1994). In adult UCP-DTA mice, we measured food intake and food assimilation, locomotor activity, metabolic rate, and body temperature in comparison to control animals. No differences could be observed in food intake or assimilation and locomotor activity. Weight-specific metabolic rates at temperatures between 20 and 37 degrees C, however, were consistently lower in transgenic mice. Continuous telemetric recording of core body temperature showed that transgenic mice displayed a downshift in body temperature levels of approximately 0.9 degree C. In summary, we provide evidence that attenuated body temperature levels alone can be responsible for development of obesity and that BAT thermogenesis is a major determinant of body temperature levels in rodents.


Activation of excitatory amino acid receptors in bovine dental pulp evokes the release of iCGRP.
The activation of excitatory amino acid (EAA) receptors within the central nervous system is associated with numerous centrally mediated phenomena, including hyperalgesia. However, relatively little is known about the peripheral mechanisms which these receptors may regulate when activated. This research evaluated the hypothesis that EAA receptors in bovine dental pulp activate a population of peptidergic sensory neurons as measured by the release of immunoreactive calcitonin gene-related peptide (iCGRP), a neuropeptide associated with neurogenic inflammation. In vitro superfusion of bovine dental pulp was used to evaluate the regulation of iCGRP secretion by the EAA receptor agonists AMPA, kainate, NMDA, and L-glutamate. Both AMPA and kainate stimulated the release of iCGRP in a concentration-dependent manner (AMPA EC50 = 0.27 +/- 3.3 nM; kainate EC50 = 3.2 +/- 1.1 microM). Pre-treatment and co-administration of the AMPA/kainate receptor antagonist CNQX significantly reduced the iCGRP release evoked by either of these agonists. In contrast, neither NMDA nor L-glutamate induced any consistent changes in iCGRP release. These results suggest that the activation of AMPA and kainate receptors in dental pulp may contribute to peripheral release of vasoactive neuropeptides which mediate a neurogenic component of inflammation.


Modern psychosurgery before Egas Moniz: a tribute to Gottlieb Burckhardt.
The history of modern psychosurgery has been written in several ways, weaving around many pioneers in the field during the 19th century. Often neglected in this history is Gottlieb Burckhardt (1836-1907), who performed the first psychosurgical procedures as early as 1888, several decades before the work of Egas Moniz (1874-1955). The unconventional and original case series of Burckhardt, who claimed success in 50% of patients (3 of 6), had met with overt criticism from his contemporary medical colleagues. The authors describe 2 illustrative cases of cortical extirpation performed by Burckhardt and review his pioneering case series for surgical outcome, despite the ambiguity in postoperative evaluation criteria. Although Burckhardt discontinued the project after publication of his surgical results in 1891, neurosurgeons around the world continued to investigate psychosurgery and revitalized his ideas in 1910; psychosurgery subsequently developed into a full-fledged neurosurgical specialty.


[Curative effects of transplantation of hepatocytes differentiated from embryonic stem cells on treatment of fulminant hepatic failure: experiment with mice].
To investigate the curative effects of transplantation of hepatocytes differentiated from embryonic stem cells (ESCs) on treatment of fulminant hepatic failure (FHF). Mouse ESCs transfected with green fluorescent protein were cultured. RT-PCR was used to detect the mRNA expression of alpha-fetoprotein (AFP), transthyretin (TTR), hepatic nuclear factor (HNF), albumin (ALB), glucose-6-phosphate (G6P), and tyrosine aminotransferase (TAT) at different time points. Immunocytochemistry (ICC) was used to detect the expression of AFP, ALB, cytokeratin 8 (CK8), and CK11 in the cells. The morphology and distribution of the cells were observed with microscope. Forty mice were randomly divided into 2 equal groups: ESC transplantation group, undergoing transplantation of ICC positive ESCs (hepatocytes) into the hepatic capsule, and control group, undergoing injection of normal saline in the hepatic capsule. Twenty-four hours later carbon tetrachloride was injected intra-peritoneally to induce FHF. The survival status of the mice was observed. Twenty-four hours later venous blood samples were collected to examine the levels of total bilirubin (TB), alanine aminotransferase (ALT), ALB, blood sugar (BS), and prothrombin time (PT). After the death of the mice, their livers were taken out to undergo microscopy and immunohistochemistry to observe the structure of liver tissue, growth of tumor, and expression of ALB. RT-PCR showed that the mRNA expression of AFP, TTR, HNF, ALB, G6P, and TAT emerged since days 3, 3, 5, 9, and 11 respectively and then gradually increased till day 19. ICC showed that the EB cells began to express AFP since day 7, to express CK8 and CK11 since day 9, and to express ALB since day 11. The ICC-positive cells were consistent with the mouse hepatocytes morphologically and were distributed only in the central and marginal areas of the EB cell community. Injected with carbon tetrachloride, the mice showed manifestations of FHF. However, the symptoms of central nervous system emerged later in the mice implanted with the hepatocytes in comparison with the control mice; 8 of the 20 mice in the transplantation group showed ascites in comparison with 14 in the control group. The mean survival time of the transplantation group was 62 hours, significantly longer than that of the control group (23 hours, P < 0.05). Compare with the normal mice, the FHF mice in both groups showed higher ALT and TB and lower ALB and BS (all P < 0.01), however, the levels of ALT and TB were lower, the level of BS was higher, and PT was shorter significantly in the transplantation group than in the control group (all P < 0.05). Pathology showed that no tumor formation was found in both groups and that the transplanted hepatocytes were incorporated well into the liver parenchymal structure and expressed ALB. Hepatocytes originating from ESCs exercise the functions of normal hepatocytes. Transplantation of hepatocytes differentiated from ESCs is able to improve the life quality and lengthen the survival time of FHF mice.


Vasal irrigation with sterile water and saline solution for acceleration of postvasectomy azoospermia.
Vasectomy is the safest and most reliable method of all the contraception methods, but azoospermia is not achieved immediately by this method. We decided to determine whether irrigation of the vas deferens with sterile water or hypertonic saline solution irrigation during vasectomy would reduce the time needed to obtain azoospermia. A total of 126 fertile men presented for vasectomy were divided in 3 groups. No-scalpel vasectomy was done for all of the participants and irrigation of the vas deferens was carried out during the procedure in 2 groups with either sterile water or hypertonic saline solution (9 g/L sodium chloride solution). Forty-two participants underwent vasectomy without irrigation. Semen analysis was performed at 4, 8, 12, and 16 weeks after vasectomy. Azoospermia was achieved in all of the men with sterile water after 12 weeks, while at the end of the study (16 weeks) it was achieved in 37 (88.1%) of those with saline solution and in 11 (26.2%) of those without irrigation. There were significant differences in the rates of azoospermia between the participant with sterile water and saline solution at 8 weeks (38.1% versus zero; P < .001), 12 weeks (100% versus 30.9%; P < .001), and 16 weeks (100% versus 88.1%; P = .02). No pregnancy developed during the follow-up and no complication was reported. Vasal irrigation with sterile water and hypertonic saline solution during vasectomy were effective in removing sperm from the distal vas and increasing the rate at which men achieved azoospermia. Sterile water was a promising option with no complications.


Micro-machining.
Manipulating bulk material at the atomic level is considered to be the domain of physics, chemistry and nanotechnology. However, precision engineering, especially micro-machining, has become a powerful tool for controlling the surface properties and sub-surface integrity of the optical, electronic and mechanical functional parts in a regime where continuum mechanics is left behind and the quantum nature of matter comes into play. The surprising subtlety of micro-machining results from the extraordinary precision of tools, machines and controls expanding into the nanometre range-a hundred times more precise than the wavelength of light. In this paper, we will outline the development of precision engineering, highlight modern achievements of ultra-precision machining and discuss the necessity of a deeper physical understanding of micro-machining.


Cold en bloc excision (CEBE) of bladder tumours using Zedd excision scissors: a prospective, pilot, safety and feasibility study.
Transurethral resection of bladder tumour (TURBT) is the traditional technique of choice for endoscopically suspected bladder tumours. Cold En Bloc Excision (CEBE) using novel Zedd scissors is proposed for endoscopic treatment of patients with non-muscle invasive bladder cancer (NMIBC). The aim of this study was to evaluate feasibility and safety of CEBE of bladder tumours using Zedd scissors. A pilot prospective study of patients who underwent a CEBE of suspicious bladder tumours using Zedd scissors was conducted. A total of 23 patients underwent CEBE for suspected bladder tumours using Zedd scissors. New and recurrent tumours <3 cm were included in the study. The outcome measures were the presence of detrusor muscle (DM) and obturator nerve reflex (ONR), bladder perforation rates, specimen cautery artefacts, recurrence rates and complication rates. The mean age was 64 years ± 10.41 (range: 49-83 years). The median follow up was 4 months (range 1-9 months). The mean tumour size was 1.8 cm ± 0.40 (range: 0.8-2.6 cm). Tumours were located in the lateral wall (n = 11), dome (n = 2), posterior wall (n = 6), trigone (n = 2), anterior wall (n = 4) and the junction of lateral and posterior wall (n = 4). There was no ONR or bladder perforation and none of the patients had any complications. DM was present in 21 patients (91%). There was no tumour identified at the circumferential margins. There was no cautery artefact reported in any case. No patients had a recurrence at first follow up cystoscopy and two patients had out of field recurrence at subsequent cystoscopies. CEBE with Zedd scissors is a promising en bloc excision technique for bladder tumour. It is a safe and feasible for excision of tumours less than 3 cm. The early oncological outcomes are comparable with existing en bloc resection techniques (ERBT) for NMIBC.


Overview of structural and functional lesions in endocrine organs of animals.
The objective of this review is to summarize the pathogenic mechanisms responsible for perturbations of endocrine function and development of structural lesions that result in important diseases in domestic and laboratory animals. For each major category, several specific disease problems have been selected to illustrate the functional and morphologic lesions that are characteristic for either a naturally occurring endocrinopathy or endocrine disturbances induced by the administration of large doses of xenobiotic chemicals. The major pathogenic mechanisms responsible for disruption of endocrine function include primary hyperfunction, secondary hyperfunction, primary hypofunction, secondary hypofunction, endocrine hyperactivity secondary to other conditions, hypersecretion of hormones by nonendocrine tumors, failure of target cells to respond to a hormone, failure of fetal endocrine function, abnormal degradation (increased or decreased rate) of hormone, and iatrogenic syndromes of hormone excess (direct and indirect). Disorders of the endocrine system are encountered in a wide variety of domestic and laboratory animal species and often present challenging diagnostic problems. The development of proliferative lesions, usually hyperplasia and benign tumors, in endocrine organs and hormone-responsive tissues are common findings in chronic studies with high doses of many nongenotoxic xenobiotic chemicals administered to sensitive rodent species and may have limited significance for human safety assessment.


Differential prevalence and associations of overweight and obesity by gender and population group among school learners in South Africa: a cross-sectional study.
Factors influencing the increasing prevalence of overweight/obesity among children and adolescents in sub-Saharan Africa remain unclear. We assessed the prevalence and determinants of overweight and obesity and effects on cardio-metabolic profile in school learners in the Western Cape, South Africa. Cross-sectional data were collected from 7 to 18-year-old South African school learners attending 14 schools, randomly selected from 107 government schools in the areas. The learners were selected through stratified random sampling techniques. Logistic regressions were used to assess the determinants of overweight/obesity and its association with cardio-metabolic profile. Among the 1559 participants, the overall prevalence of overweight/obesity was 22.9%. Being a girl (Odds ratio 2.51, 95% CI: 1.92-3.29), or Black African (1.35, 1.04-.75) was associated with increased odds of being overweight/obese. The identified health consequences among the overweight/obese learners differed between the ethnic groups. Overweight/obese coloured (mixed ancestry) learners were more likely to have hypertension (3.27, 1.18-9.08), hypertriglyceridemia (1.94, 0.99-3.78) and low high-density lipoprotein cholesterol (HDL-C) (3.65, 2.33-5.72), overweight/obese Black African learners had higher odds for hypertension (3.62, 1.31-10.04) and low HDL-C (1.56, 1.01-2.40) and overweight/obese White learners were prone to low HDL-C (5.04, 1.35-18.80). Overweight/obesity is highly prevalent among school learners in Western Cape (South Africa), with being female or Black African increasing the odds. That overweight/obesity is also associated with adverse cardio-metabolic risk profile aggravates the problem and suggests worse cardiovascular outcomes in South African young adults in the future.


Hepatoprotective and antioxidant effects of wheat, carrot, and mango as nutraceutical agents against CCl4-induced hepatocellular toxicity.
During the last decade, there has been a growing interest in replacing synthetic antioxidants by natural ones because they are cheaper and safe. The main aim of this work was to investigate the possible role of carrot, mango, and wheat extracts against carbon tetrachloride (CCl4)-induced oxidative stress and hepatotoxicity. Forty albino rats were recruited and divided into 5 groups. Group 1 was fed a basal diet and group 2 was fed a basal diet and CCl4. Groups 3, 4, and 5 were treated with carrot, mango, and wheat extracts, respectively, in addition to a basal diet and CCl4. Hepatocellular toxicity decreased significantly following treatment. Lipid profile and liver enzymes markers decreased remarkably and total protein and high-density lipoprotein (HDL) increased dramatically. The oxidative stress has decreased noticeably through the decrease in Malondialdehyde (MDA). Microscopic examination of the treated rats exhibited a normal histopathological structure. These data suggest that carrot, mango, and wheat extracts could be used as nutraceuticals for the prophylaxis and treatment against hepatotoxicity and oxidative stress. This is the first study of its kind that highlights the importance of including such plants in the dairy and food industry for the prevention of hepatocellular toxicity and oxidative stress.


Role of ICAM-1 and E-selectin gene polymorphisms in pathogenesis of PAOD in Egyptian patients.
Intercellular adhesion molecule-1 (ICAM-1) and E-selectin have been shown to predict cardiovascular disease (CVD) such as myocardial infarction, stroke, and peripheral arterial occlusive disease (PAOD). Two mutations, S128R in E-selectin and K469E in ICAM-1, were investigated in 156 patients with PAOD and 100 control subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in an Egyptian population. The distribution of E-selectin genotypes in patients affected by PAOD was 84.6% for the AA genotype and 15.4% for the AC genotype. In the control arm the distribution was 97% for the AA genotype and 3% for the AC genotype. There was a statistically significance difference in the distribution of the AC genotype in PAOD patients when compared with the control subjects. Additionally, the distribution of ICAM-1 genotypes in patients affected by PAOD was 30.8% with the EE, 48% with the EK, and 21.2% with the KK genotypes. The distribution of ICAM-1 genotypes in control subjects was 13% EE, 33% EK and 54% KK. The EE genotype was significantly more common in PAOD patients than in the controls. S128R and K469E polymorphisms were associated with increased risk in PAOD. Early detection of these polymorphic genes helps in early prophylaxis against PAOD.


Structures of prolyl oligopeptidase substrate/inhibitor complexes. Use of inhibitor binding for titration of the catalytic histidine residue.
Structure determination of the inactive S554A variant of prolyl oligopeptidase complexed with an octapeptide has shown that substrate binding is restricted to the P4-P2' region. In addition, it has revealed a hydrogen bond network of potential catalytic importance not detected in other serine peptidases. This involves a unique intramolecular hydrogen bond between the P1' amide and P2 carbonyl groups and another between the P2' amide and Nepsilon2 of the catalytic histidine 680 residue. It is argued that both hydrogen bonds promote proton transfer from the imidazolium ion to the leaving group. Another complex formed with the product-like inhibitor benzyloxycarbonyl-glycyl-proline, indicating that the carboxyl group of the inhibitor forms a hydrogen bond with the Nepsilon2 of His(680). Because a protonated histidine makes a stronger interaction with the carboxyl group, it offers a possibility of the determination of the real pK(a) of the catalytic histidine residue. This was found to be 6.25, lower than that of the well studied serine proteases. The new titration method gave a single pK(a) for prolyl oligopeptidase, whose reaction exhibited a complex pH dependence for k(cat)/K(m), and indicated that the observed pK(a) values are apparent. The procedure presented may be applicable for other serine peptidases.


Long-term mifepristone (RU486) therapy resulting in massive benign endometrial hyperplasia.
Mifepristone (RU486) is a potent antiprogestagen, and at high doses it also acts as an antiglucocorticoid drug. Mifepristone, administered as a single 600 mg dose, is commonly employed to induce medical abortion in conjunction with prostaglandins. The long-term safety profile of mifepristone, especially at high doses, is less well-established. Long-term mifepristone is considered efficacious in treating uterine myomas, endometriosis (25--100 mg/day), and possibly in inoperable meningiomas (200 mg/day), as well as inoperable Cushing's syndrome. Many animal studies document an antiproliferative effect (antioestrogenic), as do some reports in humans. However, there are also data to suggest that, as an antiprogestagen, mifepristone may promote an unopposed oestrogen milieu, and thus have a proliferative effect upon the endometrium. We hereby describe the first reported case of an adolescent female with Cushingoid features and morbid osteoporosis who was treated with mifepristone for its antiglucocorticoid effect (400 mg/day) in an attempt to prevent further bone loss. The patient's striae, weight gain, and buffalo hump markedly improved, and further bone loss was halted. However, with each of the two 6-month courses of mifepristone (9 months apart) she developed massive simple endometrial hyperplasia and a markedly enlarged uterus. This reversed to normal after cessation of mifepristone treatment. In conclusion, High doses of the antiprogestagen mifepristone over a prolonged period of time may promote an unopposed oestrogen milieu leading to endometrial hyperplasia. Therefore, interval pelvic imaging in women who receive long-term mifepristone may be prudent.


Queen's Gambit Declined: The Gender-Equality Paradox in Chess Participation Across 160 Countries.
The gender-equality paradox refers to the puzzling finding that societies with more gender equality demonstrate larger gender differences across a range of phenomena, most notably in the proportion of women who pursue degrees in science, technology, engineering, and math. The present investigation demonstrates across two different measures of gender equality that this paradox extends to chess participation (N = 803,485 across 160 countries; age range: 3-100 years), specifically that women participate more often in countries with less gender equality. Previous explanations for the paradox fail to account for this finding. Instead, consistent with the notion that gender equality reflects a generational shift, mediation analyses suggest that the gender-equality paradox in chess is driven by the greater participation of younger players in countries with less gender equality. A curvilinear effect of gender equality on the participation of female players was also found, demonstrating that gender differences in chess participation are largest at the highest and lowest ends of the gender-equality spectrum.


Novel aberrant nuclear behavior in abortive conjugation of Tetrahymena thermophila: joint selection of a meiotic product and macronucleus during nuclear selection.
In conjugation of Tetrahymena thermophila, the paroral zone, cortical cytoplasm in the vicinity of the cytostome, is the site where nuclear selection occurs; one of the four meiotic products is selected in this site prior to the production of gametic pronuclei. During inbreeding cross experiments, several sterile strains were obtained which showed aberrant nuclear behavior. Conjugants of these strains normally underwent meiosis, resulting in the generation of four meiotic products. They, however, failed to complete the process of nuclear selection and aborted the subsequent conjugation sequences. During nuclear selection, macronucleus was frequently selected instead of a meiotic product. A novel aberrant nuclear behavior was observed: Macronucleus and a meiotic product were jointly selected and the both nuclei simultaneously attached to the same paroral zone. When this simultaneous attachment occurred in one partner cell of a pair, nuclear selection was never observed in the other partner cell. This result suggests that a conjugating pair has only two attachment sites on the paroral zone during nuclear selection, and that the distribution of the sites is occasionally distorted in abortive conjugation.


Neurologic deficit following percutaneous vertebral stabilization.
A retrospective review. The purpose of this study is to document a series of cases of neurologic deficit following percutaneous vertebral stabilization, to identify patterns of neurologic injury, and to describe potential methods for avoiding these injuries. Percutaneous vertebral stabilization procedures, including vertebroplasty and kyphoplasty, have become a widely used for the treatment of osteoporotic vertebral compression fractures, primary and metastatic vertebral tumors, and traumatic burst fractures. Despite an increasing array of indications, there have been few reports of adverse events. Neurologic complications associated with vertebroplasty and kyphoplasty have been described previously as case reports and have generally been considered as infrequent and minor in severity. The clinical course of 14 patients with documented loss of neurologic function following percutaneous vertebral cement augmentation was retrospectively reviewed. The average patient age was 74.9 years (range, 46-88 years) with 3 male and 11 female patients. Four patients underwent a vertebroplasty procedure while 10 were treated with kyphoplasty. Six patients developed neurologic deficits acutely (<24 hours of procedure). The remaining 8 patients developed neurologic symptoms at an average of 37.1 days (range, 3-112 days) postprocedure. Neurologic deficits were recorded as ASIA A in 4 patients, ASIA B in 2 patients, ASIA C in 1 patient, and ASIA D in 7 patients. Twelve of 14 patients (85.7%) required revision open surgical intervention for treatment of their neurologic injury. Percutaneous vertebroplasty and kyphoplasty have been reported to be safe options for the treatment of painful osteoporotic vertebral fractures. Although complications are infrequent, there remains the potential for catastrophic neurologic injury. Physicians performing these procedures need to be aware of these potential complications and be prepared to respond in an emergent manner (surgically) if a need arises.


Characterization of a gene encoding dihydrolipoamide dehydrogenase of the cyanobacterium Synechocystis sp. strain PCC 6803.
The authors previously reported the isolation and partial characterization of a periplasmically located dihydrolipoamide dehydrogenase (LPD) from the cyanobacterium Synechocystis sp. strain PCC 6803. In the present work the gene (lpdA; database accession number Z48564) encoding the apoprotein of this LPD in Synechocystis PCC 6803 has been identified, sequenced and analysed. The lpdA gene codes for a protein starting with methionine, which is post-translationally removed. The mature protein contains an N-terminal serine and consists of 473 amino acids with a deduced molecular mass of 51421 Da (including one FAD). The LPD is an acidic protein with a calculated isoelectric point of 5.17. Comparison of the amino acid sequence of the Synechocystis LPD with protein sequences in the databases revealed that the enzyme shares identities of 31-35% with all 18 LPDs so far sequenced and published. As a first step in determining the role of this cyanobacterial LPD, attempts were made to generate an LPD-free Synechocystis mutant by insertionally inactivating the lpdA gene with a kanamycin-resistance cassette. However, the selected transformants appeared to be heteroallelic, containing both the intact lpdA gene and the lpdA gene inactivated by the drug-resistance cassette. The heteroallelic mutant studied, which had about 50% of the wild-type LPD activity, caused acidification of the growth medium. Growth over a prolonged time was only possible after an increased buffering of the medium. Since it is reported in the literature that inactivation of the pyruvate dehydrogenase complex (PDC) leads to acidosis, a function of the LPD in a cytoplasmic-membrane-associated PDC is conceivable.


Sialic acid binding properties of soluble coronavirus spike (S1) proteins: differences between infectious bronchitis virus and transmissible gastroenteritis virus.
The spike proteins of a number of coronaviruses are able to bind to sialic acids present on the cell surface. The importance of this sialic acid binding ability during infection is, however, quite different. We compared the spike protein of transmissible gastroenteritis virus (TGEV) and the spike protein of infectious bronchitis virus (IBV). Whereas sialic acid is the only receptor determinant known so far for IBV, TGEV requires interaction with its receptor aminopeptidase N to initiate infection of cells. Binding tests with soluble spike proteins carrying an IgG Fc-tag revealed pronounced differences between these two viral proteins. Binding of the IBV spike protein to host cells was in all experiments sialic acid dependent, whereas the soluble TGEV spike showed binding to APN but had no detectable sialic acid binding activity. Our results underline the different ways in which binding to sialoglycoconjugates is mediated by coronavirus spike proteins.


The three human monocyte subsets: implications for health and disease.
Human blood monocytes are heterogeneous and conventionally subdivided into two subsets based on CD16 expression. Recently, the official nomenclature subdivides monocytes into three subsets, the additional subset arising from the segregation of the CD16+ monocytes into two based on relative expression of CD14. Recent whole genome analysis reveal that specialized functions and phenotypes can be attributed to these newly defined monocyte subsets. In this review, we discuss these recent results, and also the description and utility of this new segregation in several disease conditions. We also discuss alternative markers for segregating the monocyte subsets, for example using Tie-2 and slan, which do not necessarily follow the official method of segregating monocyte subsets based on relative CD14 and CD16 expressions.


A Hyaluronic Acid Demilune Scaffold and Polypyrrole-Coated Fibers Carrying Embedded Human Neural Precursor Cells and Curcumin for Surface Capping of Spinal Cord Injuries.
Tissue engineering, including cell transplantation and the application of biomaterials and bioactive molecules, represents a promising approach for regeneration following spinal cord injury (SCI). We designed a combinatorial tissue-engineered approach for the minimally invasive treatment of SCI-a hyaluronic acid (HA)-based scaffold containing polypyrrole-coated fibers (PPY) combined with the RAD16-I self-assembling peptide hydrogel (Corning® PuraMatrix™ peptide hydrogel (PM)), human induced neural progenitor cells (iNPCs), and a nanoconjugated form of curcumin (CURC). In vitro cultures demonstrated that PM preserves iNPC viability and the addition of CURC reduces apoptosis and enhances the outgrowth of Nestin-positive neurites from iNPCs, compared to non-embedded iNPCs. The treatment of spinal cord organotypic cultures also demonstrated that CURC enhances cell migration and prompts a neuron-like morphology of embedded iNPCs implanted over the tissue slices. Following sub-acute SCI by traumatic contusion in rats, the implantation of PM-embedded iNPCs and CURC with PPY fibers supported a significant increase in neuro-preservation (as measured by greater βIII-tubulin staining of neuronal fibers) and decrease in the injured area (as measured by the lack of GFAP staining). This combination therapy also restricted platelet-derived growth factor expression, indicating a reduction in fibrotic pericyte invasion. Overall, these findings support PM-embedded iNPCs with CURC placed within an HA demilune scaffold containing PPY fibers as a minimally invasive combination-based alternative to cell transplantation alone.


Changes in the expression of potassium channels during mouse T cell development.
In this report we have combined the whole-cell electrophysiological recording technique with flow microfluorometry to isolate phenotypically defined thymocytes and T lymphocytes. Results obtained showed that J11d-/Lyt-2-/L3T4- cells express none or very few delayed rectifier K+ channels, whereas most other Lyt-2-/L3T4- cells, as well as typical cortical thymocytes (Lyt-2+/L3T4+), do express K+ channels. Mature (Lyt-2+/L3T4- or Lyt-2-/L3T4+) thymocytes, which are heterogeneous for J11d expression, were also found to be heterogeneous for K+ channel expression. Consistent with this finding was the observation that the cortisone-resistant subpopulation of thymocytes, which express low levels of J11d, were enriched for cells expressing low levels of K+ channels. Mature phenotype peripheral T lymphocytes expressed very low levels of K+ channels, but upon activation with Con A were found to express high levels of K+ channels. The results suggest that K+ channel expression in T cells is developmentally regulated. Increased expression of the channel is induced in response to mitogenic signals throughout the T cell lineage. Expression of the channel, therefore, serves as a useful marker in defining steps in the T cell differentiation pathway.


Principal expression of two mRNA isoforms (ABCB 5alpha and ABCB 5beta ) of the ATP-binding cassette transporter gene ABCB 5 in melanoma cells and melanocytes.
ATP-binding cassette (ABC) transporters play a pivotal role in physiology and pathology. We identified and cloned two novel mRNA isoforms (ABCB 5alpha and ABCB 5beta) of the ABC transporter ABCB 5 in human melanoma cells. The deduced ABCB 5alpha protein appears to be an altered splice variant containing only a putative ABC, whereas the ABCB 5beta isoform shares approximately 70% similarity with ABCB1 (MDR1) and has a deduced topological arrangement similar to that of the whole carboxyl terminal half of the ABCB1 gene product, P-glycoprotein, including an intact ABC. Northern blot, real-time PCR, and conventional RT-PCR were used to verify the expression profiles of ABCB 5alpha/beta. We found that the melanomas included among the NCI-60 panel of cell lines preferentially expressed both ABCB 5alpha and ABCB 5beta. However, ABCB 5alpha/beta expression was undetectable in two amelanotic melanomas (M14 and LOX-IMVI). The expression profile of ABCB 5alpha/beta in all of the other melanomas of the panel was confirmed both by RT-PCR and by sequencing. Neither ABCB 5alpha nor ABCB 5beta expression was found in normal tissues such as liver, spleen, thymus, kidney, lung, colon, small intestines or placenta. ABCB 5alpha/beta mRNAs were also expressed in normal melanocytes and in retinal pigment epithelial cells, suggesting that ABCB 5alpha/beta expression is pigment cell-specific and might be involved in melanogenesis. Our findings indicate that expression of ABCB 5alpha/beta might possibly provide two novel molecular markers for differential diagnosis of melanomas and constitute potential molecular targets for therapy of melanomas.


Effect of combinations of cytokines and hormones on synthesis of serum amyloid A and C-reactive protein in Hep 3B cells.
We have previously shown that induction of synthesis of the two major human acute phase proteins, serum amyloid A (SAA) and C-reactive protein (CRP), can be accomplished in the human hepatoma cell line Hep 3B, in the presence of dexamethasone, either by conditioned medium from LPS-stimulated monocytes or by the combination of IL-6 and IL-1. Neither of these cytokines alone caused significant induction of either SAA or CRP. In the present study we extended our earlier observations by evaluating the role of dexamethasone, the effect of different concentrations of IL-6 and IL-1 alpha in combination, and the possible role of TNF-alpha in regulating synthesis of SAA and CRP. Dexamethasone alone had no effect on induction of SAA or CRP. Incubation of Hep 3B cells with conditioned medium from LPS-stimulated monocytes, in the absence of dexamethasone, led to modest induction of SAA or CRP, but addition of dexamethasone potentiated this response in a dose-dependent manner. Similar results were obtained for the effect of dexamethasone on the induction of SAA by IL-6 plus IL-1 alpha. Checkerboard titration of IL-6 and IL-1 alpha revealed that increases in concentration of either cytokine led to dose-related increases in synthesis of both SAA and CRP as long as a minimal amount of the other cytokine was present. TNF-alpha alone had no significant effect on synthesis of either SAA or CRP, but the combination of IL-6 plus TNF-alpha led to substantial induction of SAA. This combination was less effective than the combination of IL-6 plus IL-1 alpha. No detectable effect of IL-6 plus TNF-alpha was observed on CRP synthesis. Both combinations of cytokines, IL-6 plus IL-1 alpha, and IL-6 plus TNF-alpha, caused increased SAA mRNA accumulation that roughly paralleled increase in synthesis. These data indicate that IL-6, IL-1 alpha, TNF-alpha, and dexamethasone in various combinations are all capable of influencing synthesis of SAA in Hep 3B cells, whereas only IL-6, IL-1 alpha, and dexamethasone can influence CRP synthesis.


Orbital reconstruction with individually copy-milled ceramic implants.
Diagnostic advances such as computed tomography and new surgical techniques have dramatically improved both the functional and aesthetic outcome of orbital reconstructions. Taking a further approach, we designed ceramic implants (Bioverit) on the basis of stereolithographic models. After copy milling a resin template with a commercially available dental unit (Celay), the prefabricated implants were inserted for reconstruction of the lamina papyracea (n = 1), zygomatic complex (n = 2), infraorbital floor (n = 5), and rim (n = 3). Intraoperatively, only slight modifications of the implants had to be performed. The results were encouraging, as all cases showed a good aesthetic and functional postoperative outcome. Preoperative evaluation of the osseous defect and prefabrication of the required implant reduced operating time and patient morbidity significantly.


Sustainability assessment of advanced wastewater treatment technologies.
As a consequence of the EU Water Framework Directive more focus is now on discharges of hazardous substances from wastewater treatment plants and sewers. Thus, many municipalities in Denmark may have to adopt to future advanced treatment technologies. This paper describes a holistic assessment, which includes technical, economical and environmental aspects. The technical and economical assessment is performed on 5 advanced treatment technologies: sand filtration, ozone treatment, UV exclusively for disinfection of pathogenic microorganisms, membrane bioreactor (MBR) and UV in combination with advanced oxidation. The technical assessment is based on 12 hazardous substances comprising heavy metals, organic pollutants, endocrine disruptors as well as pathogenic microorganisms. The environmental assessment is performed by life cycle assessment (LCA) comprising 9 of the specific hazardous substances and three advanced treatment methods; sand filtration, ozone treatment and MBR. The technical and economic assessment showed that UV solely for disinfection purposes or ozone treatment is the most advantageous advanced treatment methods if the demands are restricted to pathogenic microorganisms. In terms of sustainability, sand filtration is the most advantageous method based on the technical and environmental assessment due to the low energy consumption and high efficiency with regards to removal of heavy metals.


Zinc transporter-8 autoantibodies improve prediction of type 1 diabetes in relatives positive for the standard biochemical autoantibodies.
We assessed diabetes risk associated with zinc transporter-8 antibodies (ZnT8A), islet cell antibodies (ICA), and HLA type and age in relatives of people with type 1 diabetes with the standard biochemical autoantibodies (BAA) to insulin (IAA), GAD65 (GAD65A), and/or insulinoma-associated protein 2 antigen (IA-2A). For this analysis, 2,256 relatives positive for at least one BAA, of whom 142 developed diabetes, were tested for ZnT8A, ICA, and HLA genotype followed by biannual oral glucose tolerance tests. ZnT8A were also tested in 911 randomly chosen antibody-negative relatives. ZnT8A were associated with the other BAA (548 of 2,256 [24.3%] BAA(+) vs. 8 of 911 [0.8%] BAA(-), P < 0.001) and BAA number (177 of 1,683 [10.5%] single-, 221 of 384 [57.6%] double-, and 150 of 189 [79.4%] triple-BAA positivity, P < 0.001). The 4-year diabetes risk was higher in single BAA(+) relatives with ZnT8A than ZnT8A(-) relatives (31 vs. 7%, P < 0.001). In multivariable analysis, age ≤ 20 years (hazard ratio 2.13, P = 0.03), IA-2A (2.15, P = 0.005), IAA (1.73, P = 0.01), ICA (2.37, P = 0.002), and ZnT8A (1.87, P = 0.03) independently predicted diabetes, whereas HLA type (high and moderate vs. low risk) and GAD65A did not (P = 0.81 and 0.86, respectively). In relatives with one standard BAA, ZnT8A identified a subset at higher diabetes risk. ZnT8A predicted diabetes independently of ICA, the standard BAA, age, and HLA type. ZnT8A should be included in type 1 diabetes prediction and prevention studies.


Joint evolution of differential seed dispersal and self-fertilization.
Differential seed dispersal, in which selfed and outcrossed seeds possess different dispersal propensities, represents a potentially important individual-level association. A variety of traits can mediate differential seed dispersal, including inflorescence and seed size variation. However, how natural selection shapes such associations is poorly known. Here, we developed theoretical models for the evolution of mating system and differential seed dispersal in metapopulations, incorporating heterogeneous pollination, dispersal cost, cost of outcrossing and environment-dependent inbreeding depression. We considered three models. In the 'fixed dispersal model', only selfing rate is allowed to evolve. In the 'fixed selfing model', in which selfing is fixed but differential seed dispersal can evolve, we showed that natural selection favours a higher, equal or lower dispersal rate for selfed seeds to that for outcrossed seeds. However, in the 'joint evolution model', in which selfing and dispersal can evolve together, evolution necessarily leads to higher or equal dispersal rate for selfed seeds compared to that for outcrossed. Further comparison revealed that outcrossed seed dispersal is selected against by the evolution of mixed mating or selfing, whereas the evolution of selfed seed dispersal undergoes independent processes. We discuss the adaptive significance and constraints for mating system/dispersal association.


[Relationship between nystagmus and utricular function].
The horizontal neck nystagmus arising in response to angular acceleration was recorded electromyographically in pigeons (Columba livia). After bilateral section of the utricular nerves (Roumuli utriculi) the nystagmic reactions to the right and to the left remained symmetrical although they were delayed when compared to the reactions of intact animals. Unilateral section of the utricular nerves caused asymmetric reactions from the semicircular canals: the nystagmus toward the dissected nerve was delayed to a greater extent than that toward the intact nerve.


On the role of dopamine in the pathophysiology of anorexia nervosa.
Based on a review of the pathophysiology of the major symptoms of anorexia nervosa, it was suggested that increased activity of dopamine at central dopamine receptors plays a role in the pathophysiology of this disorder. Although dopamine receptor site hypersensitivity, or synthesis, of a false transmitter could account for this, a defect in negative feedback control mechanisms is more consistent with the known characteristics of anorexia nervosa. The possible role of pure dopamine antagonists in symptomatic treatment and of dopamine agonists in reversing this disorder was discussed.


Prevalence and intensity of Schistosoma haematobium infection in six villages of upper Egypt.
A cross-sectional survey for Schistosoma haematobium infection in 5,998 individuals, representing 31,803 persons in six rural villages of the Qena governorate, Upper Egypt, was completed. There were 2,223 persons (37.1%) excreting S. haematobium eggs identified by the nuclepore membrane filtration technique of a single urine specimen. Prevalence of infection ranged from 23.9% to 64.0% among the six villages. Quantitatively the overall geometric mean egg-count was 48.1 eggs/10 ml urine. A survey of proximal canals was conducted and 9 of 4,312 Bulinus snails were infected with schistosomes (0.21%). The stools of 2 of 507 adolescent males were positive for S. mansoni. No Biomphalaria snails were found. When these findings are compared to past studies, S haematobium prevalence appears to have substantially increased.


Genetic Diversity, Reassortment, and Recombination in Alfalfa mosaic virus Population in Spain.
The variability and genetic structure of Alfalfa mosaic virus (AMV) in Spain was evaluated through the molecular characterization of 60 isolates collected from different hosts and different geographic areas. Analysis of nucleotide sequences in four coding regions--P1, P2, movement protein (MP), and coat protein (CP)--revealed a low genetic diversity and different restrictions to variation operating on each coding region. Phylogenetic analysis of Spanish isolates along with previously reported AMV sequences showed consistent clustering into types I and II for P1 and types I, IIA, and IIB for MP and CP regions. No clustering was observed for the P2 region. According to restriction fragment length polymorphism analysis, the Spanish AMV population consisted of seven haplotypes, including two haplotypes generated by reassortment and one involving recombination. The most frequent haplotypes (types for P1, MP, and CP regions, respectively) were I-I-I (37%), II-IIB-IIB (30%), and one of the reassortants, II-I-I (17%). Distribution of haplotypes was not uniform, indicating that AMV population was structured according to the geographic origin of isolates. Our results suggest that agroecological factors are involved in the maintenance of AMV genetic types, including the reassortant one, and in their geographic distribution.


Detection of ostreid herpesvirus-1 in plankton and seawater samples at an estuary scale.
Ostreid herpesvirus-1 (OsHV-1) is known to associate with particles in seawater, leading to infection and disease in the Pacific oyster Crassostrea gigas. The estuarine environment is highly complex and changeable, and this needs to be considered when collecting environmental samples for pathogen detection. The aims of this study were to (1) compare different aspects of collecting natural seawater and plankton samples for detection of OsHV-1 DNA and (2) determine whether detection of OsHV-1 DNA in such environmental samples has merit for disease risk prediction. The results of one experiment suggest that sampling on the outgoing tide may improve the detection of OsHV-1 DNA in seawater and plankton tow samples (odds ratio 2.71). This statistical comparison was not possible in 2 other experiments. The method (plankton tow or beta bottle) and depth of collection (range: 250-1250 mm) had no effect on the likelihood of detection of OsHV-1. OsHV-1 DNA was found at low concentrations in plankton tow and seawater samples, and only when outbreaks of mortality associated with OsHV-1 were observed in nearby experimental or farmed populations of C. gigas. This suggests that single point in time environmental samples of seawater or plankton are not sufficient to rule out the presence of OsHV-1 in an estuary. The association of OsHV-1 with particles in seawater needs to be better understood in order to determine whether more selective and sensitive methods can be devised to detect it, before environmental samples can be reliably used in disease risk prediction.


Hyperthermia Induced by Near-Infrared Laser-Irradiated CsWO3 Nanoparticles Disintegrates Preformed Lysozyme Amyloid Fibrils.
This research study attempts to prove the concept of the applicability of hyperthermia to treating the lysozyme amyloid fibrils (LAF)'s self-assembled fibrillary aggregates by a feedback-modulated temperature controller ranging from 26 °C to 80 °C, and separately, by near-infrared (NIR) laser-irradiated cesium tungstate (CsWO3) nanoparticle (NPs). The dependence of the final morphology of the amyloidal assembly on external heating and the photothermal effect of the NPs on treating the fibrillary assembly were investigated and analyzed. Experimentally, atomic force microscopy (AFM), optical stereoscopy, and scanning electron microscopy (SEM) were used primarily to ensure mutual interaction between LAF and NPs, optically elucidate the surface contour and final fibrillary assembly upon the influence of thermal treatment, and further reveal fine-details of the optical samples. Finally, conclusive remarks are drawn that the fibrillary structures doped with the NPs exhibit an increasing degree of unique orthogonality. As the temperature rises, utter deformation of the dendritic structures of fibrillary assemblies at 70 °C was found, and NIR laser-irradiated CsWO3 NPs have been demonstrated to be useful in topically destructing pre-assembled LAFs, which may be conducive to the future development of neurodegenerative therapeutic techniques.


Multiple roles of WIN3 in regulating disease resistance, cell death, and flowering time in Arabidopsis.
The salicylic acid (SA) regulatory gene HOPW1-1-INTERACTING3 (WIN3) was previously shown to confer resistance to the biotrophic pathogen Pseudomonas syringae. Here, we report that WIN3 controls broad-spectrum disease resistance to the necrotrophic pathogen Botrytis cinerea and contributes to basal defense induced by flg22, a 22-amino acid peptide derived from the conserved region of bacterial flagellin proteins. Genetic analysis indicates that WIN3 acts additively with several known SA regulators, including PHYTOALEXIN DEFICIENT4, NONEXPRESSOR OF PR GENES1 (NPR1), and SA INDUCTION-DEFICIENT2, in regulating SA accumulation, cell death, and/or disease resistance in the Arabidopsis (Arabidopsis thaliana) mutant acd6-1. Interestingly, expression of WIN3 is also dependent on these SA regulators and can be activated by cell death, suggesting that WIN3-mediated signaling is interconnected with those derived from other SA regulators and cell death. Surprisingly, we found that WIN3 and NPR1 synergistically affect flowering time via influencing the expression of flowering regulatory genes FLOWERING LOCUS C and FLOWERING LOCUS T. Taken together, our data reveal that WIN3 represents a novel node in the SA signaling networks to regulate plant defense and flowering time. They also highlight that plant innate immunity and development are closely connected processes, precise regulation of which should be important for the fitness of plants.


Quantitative mass spectrometric analysis of the mouse cerebral cortex after ischemic stroke.
Ischemic strokes result in the death of brain tissue and a wave of downstream effects, often leading to lifelong disabilities or death. However, the underlying mechanisms of ischemic damage and repair systems remain largely unknown. In order to better understand these mechanisms, TMT-isobaric mass tagging and mass spectrometry were conducted on brain cortex extracts from mice subjected to one hour of middle cerebral artery occlusion (MCAO) and after one hour of reperfusion. In total, 2,690 proteins were identified and quantified, out of which 65% of the top 5% of up- and down-regulated proteins were found to be significant (p < 0.05). Network-based gene ontology analysis was then utilized to cluster all identified proteins by protein functional groups and cellular roles. Although three different cellular functions were identified-organelle outer membrane proteins, cytosolic ribosome proteins, and spliceosome complex proteins-several functional domains were found to be common. Of these, organelle outer membrane proteins were downregulated whereas cytosolic ribosome and spliceosome complex proteins were upregulated, indicating that major molecular events post-stroke were translation-associated and subsequent signaling pathways (e.g., poly (ADP-ribose) (PAR) dependent cell death). By approaching stroke analyses via TMT-isobaric mass tagging, the work herein presents a grand scope of protein-based molecular mechanisms involved with ischemic stroke recovery.


Diagnosis and staging of penile cancer.
A comprehensive literature study was conducted to evaluate the levels of evidence (LEs) in publications on the diagnosis and staging of penile cancer. Recommendations from the available evidence were formulated and discussed by the full panel of the International Consultation on Penile Cancer in November 2008. The final grades of recommendation (GRs) were assigned according to the LEs of the relevant publications. The following consensus recommendations were accepted: physical examination of the primary penile lesion is mandatory, evaluating the morphologic and physical characteristics of the lesion (GR A). Evaluation of the primary lesion with ultrasonography is of limited value for local tumor staging (GR C); however, evaluation of the primary tumor with magnetic resonance (MRI) imaging during artificial erection induced by intracavernosal injection of prostaglandin might be more useful (GR B). Histologic or cytologic diagnosis of the primary lesion is mandatory (GR A). For accurate histologic grading and staging, a resected specimen is preferable to a biopsy specimen alone (GR B). Penile cancer should be staged according to the TNM system; however, the 1987/2002 TNM staging system requires revision using data from larger patient cohorts to validate the recently proposed modifications (GR B). The histopathology report should provide information on all prognostic parameters, including the tumor size, histologic type, grade, growth pattern, depth of invasion, tumor thickness, resection margins, and lymphovascular and perineural invasion (GR B). Physical examination of the inguinal and pelvic areas to assess the lymph nodes is mandatory (GR B). Ultrasound-guided fine needle aspiration cytology is indicated for both palpable and nonpalpable inguinal nodes. If the findings confirm lymph node metastasis (LNM), complete inguinal lymph node dissection is indicated (GR B). In patients with nonpalpable inguinal nodes, if the ultrasound-guided fine needle aspiration cytology findings are negative for tumor, dynamic sentinel node biopsy can be performed if the equipment and technical expertise are available (GR C). In patients at high risk of inguinal LNM according to the available guidelines and nomograms, surgical staging can be performed by complete, bilateral inguinal lymph node dissection, which might also be curative (GR B). In patients at intermediate risk of LNM, sentinel node biopsy or modified (limited) inguinal lymph node dissection might be performed (GR B). In patients with nonpalpable inguinal nodes, imaging with computed tomography (CT) or MRI is not indicated, because they are not useful in detecting small-volume LNM. Also, it is very unlikely that large-volume LNM (detectable by CT/MRI) would be present in the pelvic nodes (GR B). In patients with confirmed inguinal LNM, CT of the pelvis is indicated to detect iliac LNMs (GR B). Abdominal CT and chest radiography are advisable if the pelvic CT findings are positive (GR B).


Disease Burden and Unmet Need in Eosinophilic Esophagitis.
Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease of increasing prevalence, characterized by symptoms of dysphagia and reduced quality of life. A dysregulated type 2 immune response to food and aeroallergen leads to barrier dysfunction, chronic esophageal inflammation, remodeling, and fibrosis. Patients with EoE have impaired quality of life because of dysphagia and other symptoms. They may also suffer social and psychological implications of food-related illness and expensive out-of-pocket costs associated with treatment. Disease burden in EoE is often compounded by the presence of comorbid type 2 inflammatory diseases. Current conventional treatments include elimination diet, proton pump inhibitors, and swallowed topical corticosteroids, as well as esophageal dilation in patients who have developed strictures. These treatments demonstrate variable response rates and may not always provide long-term disease control. There is an unmet need for long-term histologic, endoscopic, and symptomatic disease control; for targeted therapies that can normalize the immune response to triggers, reduce chronic inflammation, and limit or prevent remodeling and fibrosis; and for earlier diagnosis, defined treatment outcomes, and a greater understanding of patient perspectives on treatment. In addition, healthcare professionals need a better understanding of the patient perspective on disease burden, the disconnect between symptoms and disease activity, and the progressive nature of EoE and the need for continuous monitoring and maintenance treatment. In this review, we explore the progression of disease over the patient's lifespan, highlight the patient perspective on disease, and discuss the unmet need for effective long-term treatments.


Complexation of C60 fullerene with aromatic drugs.
The contributions of various physical factors to the energetics of complexation of aromatic drug molecules with C(60) fullerene are investigated in terms of the calculated magnitudes of equilibrium complexation constants and the components of the net Gibbs free energy. Models of complexation are developed taking into account the polydisperse nature of fullerene solutions in terms of the continuous or discrete (fractal) aggregation of C(60) molecules. Analysis of the energetics has shown that stabilization of the ligand-fullerene complexes in aqueous solution is mainly determined by intermolecular van der Waals interactions and, to lesser extent, by hydrophobic interactions. The results provide a physicochemical basis for a potentially new biotechnological application of fullerenes as modulators of biological activity of aromatic drugs.


Biomechanical changes in adolescent idiopathic scoliosis during walking: A protocol for systematic review and meta-analysis.
To clarify the differences in biomechanical characteristics present in adolescent idiopathic scoliosis (AIS) patients during walking. Cross-sectional studies related to the biomechanical characteristics of AIS were included by searching 7 major databases and analyzed using RevMan 5.4 software. There were a total of 15 trials involving 377 AIS patients. The results showed that during walking, AIS had increased pelvic coronal tilt (effect size [ES] = -1.34, 95% confidence intervals [CI] = -2.41 to -0.27, P = .01), knee and ankle sagittal mobility were reduced (ES = -5.22, 95% CI = -7.51 to -2.94, P < .001; ES = -3.58, 95% CI = -5.93 to -1.22, P = .003). The duration of electromyogram activity was prolonged in the gluteus medius (ES = 7.65, 95% CI = 5.33-9.96, P < .001), lumbar square (ES = 10.73, 95% CI = 6.97-14.49, P < .001), and erector spinae (ES = 14.35, 95% CI = 6.94-21.76, P < .001) muscles. The results of subgroup analysis showed that the step length of the concave side of the spine was reduced (ES = -0.36, 95% CI = -0.71 to -0.01, P = .04). AIS has characteristic biomechanical changes in spatiotemporal, phase kinematics, motor mechanics, and electromyographic signatures. Further comprehensive studies are required in the future to analyze the biomechanical and electromyographic differences among different degrees and types of scoliosis, as well as the differences between the concave and convex sides of scoliosis during walking.


Antibody-induced modulation of Leishmania donovani surface membrane antigens.
The effects of specific antibodies on the surface membrane antigens of Leishmania donovani (strain 1S, clone 2D) amastigote and promastigote developmental stages was detected in vitro by using several direct and indirect immunofluorescence methods. Stage specific anti-L. donovani sera and sera from L. donovani-infected hamsters induced parasite surface membrane antigens to aggregate, move along the longitudinal cell axis, form polar cell caps, and subsequently disappear. No membrane fluorescence was observed in cells treated identically with normal sera. In amastigotes in a single anterior cell pole cap was formed after antibody treatment. However, antibody-treated promastigotes showed tripartite membrane antigen capping consisting of a major anterior cell pole cap with minor caps at the posterior cell pole and flagellar tip regions. Loss of surface fluorescence from the two latter capped cell regions was frequently concurrent with the formation of extracellular fluorescent plasmanemes. The cell-capping process was antibody concentration, temperature, time, and energy dependent. No cell caps were formed at low temperature or in the presence of several metabolic inhibitors. Cell cap formation was also selectively inhibited by certain types of antibody-induced intercellular agglutination. Parasite membrane antigens removed by capping were regenerated and detectable at the cell surface only after a 3.5 to 4-hr period. Antibody-induced membrane antigen movement in L. donovani is apparently similar to pheonmena observed with mammalian cells. Results of direct cross-staining and cross-absorption cell-capping experiments showed that the two parasite developmental forms shared some common or at least cross-reacting membrane antigens and that each form also possessed some unique stage-specific surface antigens. Cell-capping results with sera from L. donovani infected hamsters showed that this host produces some IgG which is directed specifically against certain parasite surface membrane antigens. The results suggest that host antibody-induced parasite membrane antigen modulation might have a role in the infectious process of this human pathogen.


Investigating unexplained genetic variation and its expression in the arbuscular mycorrhizal fungus Rhizophagus irregularis: A comparison of whole genome and RAD sequencing data.
Arbuscular mycorrhizal fungi (AMF) are important symbionts of plants. Recently, studies of the AMF Rhizophagus irregularis recorded within-isolate genetic variation that does not completely match the proposed homokaryon or heterokaryon state (where heterokaryons comprise a population of two distinct nucleus genotypes). We re-analysed published data showing that bi-allelic sites (and their frequencies), detected in proposed homo- and heterokaryote R. irregularis isolates, were similar across independent studies using different techniques. This indicated that observed within-fungus genetic variation was not an artefact of sequencing and that such within- fungus genetic variation possibly exists. We then looked to see if bi-allelic transcripts from three R. irregularis isolates matched those observed in the genome as this would give a strong indication of whether bi-allelic sites recorded in the genome were reliable variants. In putative homokaryon isolates, very few bi-allelic transcripts matched those in the genome. In a putative heterokaryon, a large number of bi-allelic transcripts matched those in the genome. Bi-allelic transcripts also occurred in the same frequency in the putative heterokaryon as predicted from allele frequency in the genome. Our results indicate that while within-fungus genome variation in putative homokaryon and heterokaryon AMF was highly similar in 2 independent studies, there was little support that this variation is transcribed in homokaryons. In contrast, within-fungus variation thought to be segregated among two nucleus genotypes in a heterokaryon isolate was indeed transcribed in a way that is proportional to that seen in the genome.


Metabolic syndrome and subclinical carotid damage: a meta-analysis from population-based studies.
Metabolic syndrome (MetS) is a phenotype of growing prevalence in the general population. Information on the association between MetS and vascular damage in this setting is only based on data provided by single reports. We performed a meta-analysis of population-based studies aimed to assess the association of MetS with carotid atherosclerosis. Studies were identified by the following search terms: 'metabolic syndrome', 'general population,' 'carotid intima-media thickness' (IMT), 'carotid atherosclerosis,' 'carotid damage,' 'ultrasonography.' The OVID-MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials databases were searched for English-language articles without time restriction up to 30 September 2016. Overall, 34 635 study participants (22.9% with MetS) of both sexes were included in 21 studies (sample size range 182-11 502). Mean common carotid IMT was higher in MetS study participants as compared with their non-MetS counterparts (759 ± 41 vs. 695 ± 27 μm), the standard means difference being 0.39 ± 0.05 (confidence interval: 0.29-0.48, P < 0.0001). This was also the case when pooled data were separately analysed according to sex. Differences in carotid IMT were unaffected by the presence of publication bias or single-study effect. Our findings support the view that MetS is a risk factor for early carotid atherosclerosis in members of the general population, regardless of sex. From a practical perspective, the ultrasound search of subclinical carotid disease may refine cardiovascular risk stratification and decision-making strategies in MetS individuals.


Use of vascular access for haemodialysis in Europe: a report from the ERA-EDTA Registry.
Although arteriovenous fistulas (AVFs) are actively promoted, their use at the start of haemodialysis (HD) seems to be decreasing worldwide. In this paper, we describe recent trends in incidence and prevalence of vascular access types in Europe from 2005 to 2009 and their relationship with patient characteristics and survival. Ten European renal registries participating in the ERA-EDTA Registry provided data on incidence (n = 13,044) and/or prevalence (n = 75,715) of vascular access types. We used logistic regression to assess which factors influence the likelihood to be treated with an AVF rather than another type. The use of AVFs at the start of HD showed a significant decreasing trend from 42% in 2005 to 32% in 2009 (P < 0.0001), while the use of central venous catheters (CVCs) increased from 58 to 68% (P < 0.0001). A similar evolution pattern was observed for the prevalence; use of AVFs decreased from 66 to 62% and use of CVCs increased from 28 to 32%. There was a large international variation in the use of the different vascular access types. Female patients [adjusted odds ratio: 0.84, 95% confidence interval (CI): 0.78-0.90] and those ≥80 years (0.77, 95% CI: 0.67-0.90) were least likely to start HD with an AVF. In Europe, there is a decreasing trend in the use of AVFs and an increasing trend in the use of CVCs at the start and after the start of HD. We cannot explain all between-country variations we found, and more research is needed to clarify how healthcare around vascular access is organized in Europe.