Self-triggered assistive stimulus training improves step initiation in persons with Parkinson's disease.
Prior studies demonstrated that hesitation-prone persons with Parkinson's disease (PDs) acutely improve step initiation using a novel self-triggered stimulus that enhances lateral weight shift prior to step onset. PDs showed reduced anticipatory postural adjustment (APA) durations, earlier step onsets, and faster 1st step speed immediately following stimulus exposure. This study investigated the effects of long-term stimulus exposure. Two groups of hesitation-prone subjects with Parkinson's disease (PD) participated in a 6-week step-initiation training program involving one of two stimulus conditions: 1) Drop. The stance-side support surface was lowered quickly (1.5 cm); 2) Vibration. A short vibration (100 ms) was applied beneath the stance-side support surface. Stimuli were self-triggered by a 5% reduction in vertical force under the stance foot during the APA. Testing was at baseline, immediately post-training, and 6 weeks post-training. Measurements included timing and magnitude of ground reaction forces, and step speed and length. Both groups improved their APA force modulation after training. Contrary to previous results, neither group showed reduced APA durations or earlier step onset times. The vibration group showed 55% increase in step speed and a 39% increase in step length which were retained 6 weeks post-training. The drop group showed no stepping-performance improvements. The acute sensitivity to the quickness-enhancing effects of stimulus exposure demonstrated in previous studies was supplanted by improved force modulation following prolonged stimulus exposure. The results suggest a potential approach to reduce the severity of start hesitation in PDs, but further study is needed to understand the relationship between short- and long-term effects of stimulus exposure.


A job task analysis to describe the physical demands of specialist paramedic roles in the National Ambulance Resilience Unit (NARU).
The National Ambulance Resilience Unit (NARU) works on behalf of each National Health Service (NHS) Ambulance Trust in England to strengthen national resilience and improve patient outcome in challenging pre-hospital scenarios. To conduct a Job Task Analysis and describe the physical demands of NARU roles. A focus group was conducted to describe the physically demanding tasks performed by NARU personnel. Subsequently, the physical demands of the identified tasks were measured in 34 NARU personnel (29 male and 5 female). Eleven criterion tasks were identified; Swift Water Rescue (SWR), Re-board Inflatable Boat (RBIB), Set up Decontamination Tent (SDT), Clinical Decontamination (CD), Movement in Gas Tight Suits (MGTS), Marauding Terrorist Fire Arms (MTFA), Over Ground Rescue (OGR), Unload Incidence Response Unit Vehicle (UIRUV), Above Ground Rescue (AGR), Over Rubble Rescue (ORR) and Subterranean Rescue (SR). The greatest cardiovascular strain was measured during SWR, MGTS, and MTFA. The most thermally challenging tasks were the MTFA, CD, SR and OGR. The greatest muscular strength requirements were during MTFA and OGR. All five components of fitness (aerobic endurance, anaerobic endurance, muscular strength, muscular endurance and mobility) were required for successful completion of the physically demanding tasks performed by NARU personnel.


Outcome Measures in Psoriatic Arthritis.
In the last decade, there have been significant advances in outcome measure research in psoriatic arthritis (PsA). In this article, the outcome measures for disease activity in individual key domains of PsA are reviewed, followed by the key patient-reported outcome measures of function, quality of life, fatigue, and a new measure for disease impact, the psoriatic arthritis impact of disease. New research into composite measures of psoriatic disease is summarized, including response measures and proposed cutoff points for disease activity. Finally, the key future issues in outcome measurement in PsA are addressed.


Qualitative Evidence Synthesis (QES) for Guidelines: Paper 3 - Using qualitative evidence syntheses to develop implementation considerations and inform implementation processes.
This is the third in a series of three papers describing the use of qualitative evidence syntheses (QES) to inform the development of clinical and health systems guidelines. WHO has recognised the need to improve its guideline methodology to ensure that decision-making processes are transparent and evidence based, and that the resulting recommendations are relevant and applicable to end users. In addition to the standard data on effectiveness, WHO guidelines increasingly use evidence derived from QES to provide information on acceptability and feasibility and to develop important implementation considerations. WHO convened a group drawn from the technical teams involved in formulating recent (2010-2018) guidelines employing QES. Using a pragmatic and iterative approach that included feedback from WHO staff and other stakeholders, the group reflected on, discussed and identified key methods and research implications from designing QES and using the resulting findings in guideline development. As members of WHO guideline technical teams, our aim in this paper is to explore how we have used findings from QES to develop implementation considerations for these guidelines. For each guideline, in addition to using systematic reviews of effectiveness, the technical teams used QES to gather evidence of the acceptability and feasibility of interventions and, in some cases, equity issues and the value people place on different outcomes. This evidence was synthesised using standardised processes. The teams then used the QES to identify implementation considerations combined with other sources of information and input from experts. QES were useful sources of information for implementation considerations. However, several issues for further development remain, including whether researchers should use existing health systems frameworks when developing implementation considerations; whether researchers should take confidence in the evidence into account when developing implementation considerations; whether qualitative evidence that reveals implementation challenges should lead guideline panels to make conditional recommendations or only point to implementation considerations; and whether guideline users find it helpful to have challenges pointed out to them or whether they also need solutions. Finally, we need to explore how QES findings can be incorporated into derivative products to aid implementation.


[Analysis of old surgical operation records of the Drs. Ishin Fuwa who graduated from Hanaoka School of Medicine].
Ninety-five surgical records prepared by Dr. Ishin Rensai Fuwa from 1826 to 1859, and by his son, Dr. Ishin Kyousai Fuwa, from 1860 to 1871, were analyzed. These two surgeons lived in Fuwaishiki Village in the Mino area and performed many surgical operations under general anesthesia more than a century ago. The former was one of the trainees of Dr. Seishu Hanaoka who had performed the first operation under general anesthesia by Mafutsusan in 1804. Forty-eight patients were from the Mino area, and thirty-one from the Owari area; the others were from the Ise, Mikawa and Oomi areas. Seventy-three of 95 operations were for breast cancer, four for neck tumor, four for facial tumor, three for cleft palate and so on. The ages of breast cancer patients ranged from 15 to 68 years (mean 44 years), and 27% of 73 patients had an operation for breast cancer with removal of axillary nodes. Even at that time, informed consent for surgery seemed to have been obtained when a cancer was at the advanced stage and recurrence was suspected. These records clarify the medical situation, especially with regard to surgery, in one district of the Mino area at the end of the Edo era before Western medicine had been introduced to Japan.


Genetic diversity of the Cryptococcus species complex suggests that Cryptococcus gattii deserves to have varieties.
The Cryptococcus species complex contains two sibling taxa, Cryptococcus neoformans and Cryptococcus gattii. Both species are basidiomycetous yeasts and major pathogens of humans and other mammals. Genotyping methods have identified major haploid molecular types of C. neoformans (VNI, VNII, VNB and VNIV) and of C. gattii (VGI, VGII, VGIII and VGIV). To investigate the phylogenetic relationships among these haploid genotypes, we selected 73 strains from 2000 globally collected isolates investigated in our previous typing studies, representing each of these genotypes and carried out multigene sequence analyses using four genetically unlinked nuclear loci, ACT1, IDE, PLB1 and URA5. The separate or combined sequence analyses of all four loci revealed seven clades with significant support for each molecular type. However, three strains of each species revealed some incongruence between the original molecular type and the sequence-based type obtained here. The topology of the individual gene trees was identical for each clade of C. neoformans but incongruent for the clades of C. gattii indicating recent recombination events within C. gattii. There was strong evidence of recombination in the global VGII population. Both parsimony and likelihood analyses supported three major clades of C. neoformans (VNI/VNB, VNII and VNIV) and four major clades of C. gattii (VGI, VGII, VGIII and VGIV). The sequence variation between VGI, VGIII and VGIV was similar to that between VNI/VNB and VNII. MATa was for the first time identified for VGIV. The VNIV and VGII clades are basal to the C. neoformans or the C. gattii clade, respectively. Divergence times among the seven haploid monophyletic lineages in the Cryptococcus species complex were estimated by applying the hypothesis of the molecular clock. The genetic variation found among all of these haploid monophyletic lineages indicates that they warrant varietal status.


High prevalence of curable sexually transmitted infections among pregnant women in a rural county hospital in Kilifi, Kenya.
Women attending antenatal care (ANC) in resource-limited countries are frequently screened for syphilis and HIV, but rarely for other sexually transmitted infections (STIs). We assessed the prevalence of curable STIs, defined as infection with either Chlamydia trachomatis or Neisseria gonorrhoeae or Trichomonas vaginalis, from July to September 2015. In a cross-sectional study, women attending ANC at the Kilifi County Hospital, Kenya, had a urine sample tested for C. trachomatis/N. gonorrhoeae by GeneXpert® and a vaginal swab for T. vaginalis by culture. Bacterial vaginosis (BV) was defined as a Nugent score of 7-10 of the Gram stain of a vaginal smear in combination with self-reported vaginal discharge. Genital ulcers were observed during collection of vaginal swabs. All women responded to questions on socio-demographics and sexual health and clinical symptoms of STIs. Predictors for curable STIs were assessed in multivariable logistic regression. A total of 42/202 (20.8%, 95% confidence interval (CI):15.4-27.0) women had a curable STI. The prevalence was 14.9% for C. trachomatis (95% CI:10.2-20.5), 1.0% for N. gonorrhoeae (95% CI: 0.1-3.5), 7.4% for T. vaginalis (95% CI:4.2-12.0), 19.3% for BV (95% CI: 14.1-25.4) and 2.5% for genital ulcers (95% CI: 0.8-5.7). Predictors for infection with curable STIs included women with a genital ulcer (adjusted odds ratio (AOR) = 35.0, 95% CI: 2.7-461.6) compared to women without a genital ulcer, women who used water for cleaning after visiting the toilet compared to those who used toilet paper or other solid means (AOR = 4.1, 95% CI:1.5-11.3), women who reported having sexual debut ≤ 17 years compared to women having sexual debut ≥18 years (AOR = 2.7, 95% CI:1.1-6.6), and BV-positive women (AOR = 2.7, 95% CI:1.1-6.6) compared to BV-negative women. One in five women attending ANC had a curable STI. These infections were associated with genital ulcers, hygiene practices, early sexual debut and bacterial vaginosis.


Failure of surgery to improve outcome in hypertensive putaminal hemorrhage. A prospective randomized trial.
Hypertensive putaminal hemorrhage remains a major cause of hemorrhagic stroke carrying extremely high morbidity. Considerable controversy remains regarding the optimal form of therapy. Between 1983 and 1989 we conducted a prospective randomized trial with three treatment strategies: best medical management, best medical management plus intracranial pressure monitoring, and surgical evacuation. Only patients with significant deficit harboring a putaminal hematoma at least 3.0 cm in diameter were entered. The study was interrupted after 21 patients had been studied (9, best medical management; 4, intracranial pressure monitoring; and 8, surgical evacuation). No differences were found among groups for age, admission blood pressure, and time interval between onset of symptoms and arrival at hospital. None of the subjects were capable of returning to prestroke activity. Fifteen (71%) died or remained vegetative at 6 months, and only 4 (19%) were capable of independent life at home. Of the 9 patients in the best medical management arm, 7 were dead or vegetative. In the surgical group, 4 patients died and only 2 were capable of independent life. These results suggest that current medical and neurosurgical therapies remain ineffective in preventing the devastating neurologic consequences of hypertensive putaminal hemorrhage.


Rac1 and Cdc42 are regulators of HRasV12-transformation and angiogenic factors in human fibroblasts.
The activities of Rac1 and Cdc42 are essential for HRas-induced transformation of rodent fibroblasts. What is more, expression of constitutively activated mutants of Rac1 and/or Cdc42 is sufficient for their malignant transformation. The role for these two Rho GTPases in HRas-mediated transformation of human fibroblasts has not been studied. Here we evaluated the contribution of Rac1 and Cdc42 to maintaining HRas-induced transformation of human fibroblasts, and determined the ability of constitutively activated mutants of Rac1 or Cdc42 to induce malignant transformation of a human fibroblast cell strain. Under the control of a tetracycline regulatable promoter, dominant negative mutants of Rac1 and Cdc42 were expressed in a human HRas-transformed, tumor derived fibroblast cell line. These cells were used to determine the roles of Rac1 and/or Cdc42 proteins in maintaining HRas-induced transformed phenotypes. Similarly, constitutively active mutants were expressed in a non-transformed human fibroblast cell strain to evaluate their potential to induce malignant transformation. Affymetrix GeneChip arrays were used for transcriptome analyses, and observed expression differences were subsequently validated using protein assays. Expression of dominant negative Rac1 and/or Cdc42 significantly altered transformed phenotypes of HRas malignantly transformed human fibroblasts. In contrast, expression of constitutively active mutants of Rac1 or Cdc42 was not sufficient to induce malignant transformation. Microarray analysis revealed that the expression of 29 genes was dependent on Rac1 and Cdc42, many of which are known to play a role in cancer. The dependence of two such genes, uPA and VEGF was further validated in both normoxic and hypoxic conditions. The results presented here indicate that expression of both Rac1 and Cdc42 is necessary for maintaining several transformed phenotypes in oncogenic HRas transformed human cells, including their ability to form tumors in athymic mice. Our data also indicate that expression of either activated Rac1 or Cdc42 alone is not sufficient for malignant transformation of human fibroblasts, although each is required for specific transformed phenotypes. Furthermore, our study elucidates that the expression of several highly significant cancer related genes require the activities of Rac1 and/or Cdc42 which may also play a critical role in cellular transformation.


The Roles of Vitamin A in the Regulation of Carbohydrate, Lipid, and Protein Metabolism.
Currently, two-thirds of American adults are overweight or obese. This high prevalence of overweight/obesity negatively affects the health of the population, as obese individuals tend to develop several chronic diseases, such as type 2 diabetes and cardiovascular diseases. Due to obesity's impact on health, medical costs, and longevity, the rise in the number of obese people has become a public health concern. Both genetic and environmental/dietary factors play a role in the development of metabolic diseases. Intuitively, it seems to be obvious to link over-nutrition to the development of obesity and other metabolic diseases. However, the underlying mechanisms are still unclear. Dietary nutrients not only provide energy derived from macronutrients, but also factors such as micronutrients with regulatory roles. How micronutrients, such as vitamin A (VA; retinol), regulate macronutrient homeostasis is still an ongoing research topic. As an essential micronutrient, VA plays a key role in the general health of an individual. This review summarizes recent research progress regarding VA's role in carbohydrate, lipid, and protein metabolism. Due to the large amount of information regarding VA functions, this review focusses on metabolism in metabolic active organs and tissues. Additionally, some perspectives for future studies will be provided.


Newest-generation drug-eluting and bare-metal stents combined with prasugrel-based antiplatelet therapy in large coronary arteries: the BAsel Stent Kosten Effektivitäts Trial PROspective Validation Examination part II (BASKET-PROVE II) trial design.
In the BAsel Stent Kosten Effektivitäts Trial PROspective Validation Examination (BASKET-PROVE), drug-eluting stents (DESs) had similar 2-year rates of death and myocardial infarction but lower rates of target vessel revascularization and major adverse cardiac events compared with bare-metal stents (BMSs). However, comparative clinical effects of newest-generation DES with biodegradable polymers vs second-generation DES or newest-generation BMS with biocompatible coatings, all combined with a prasugrel-based antiplatelet therapy, on 2-year outcomes are not known. In BASKET-PROVE II, 2,400 patients with de novo lesions in native vessels ≥3 mm in diameter are randomized 1:1:1 to receive a conventional DES, a DES with a biodegradable polymer, or a BMS with biocompatible coating. In addition to aspirin, stable patients with BMS will receive prasugrel for 1 month, whereas all others will receive prasugrel for 12 months. The primary end point will be combined cardiac death, nonfatal myocardial infarction, and target vessel revascularization up to 2 years. Secondary end points include stent thrombosis and major bleeding. The primary aim is to test (1) the noninferiority of a biodegradable-polymer DES to a conventional DES and (2) the superiority of both DESs to BMS. A secondary aim is to compare the outcomes with those of BASKET-PROVE regarding the effects of prasugrel-based vs clopidogrel-based antiplatelet therapy. By the end of 2010, 878 patients (37% of those planned) were enrolled. This study will test the comparative long-term safety and efficacy of newest-generation stents on the background of contemporary antiplatelet therapy in a large all-comer population undergoing large native coronary artery stenting.


Crystal, solution, and molecular modeling structural properties and muscarinic antagonist activity of azaprophen.
The structure of azaprophen, which was originally assigned by 1H NMR analysis, was confirmed by X-ray crystallography. A comparison of 13C NMR isotropic chemical shift data for azaprophen in the solid state and in CDCl3 and DMSO-d6 solution was used to correlate solution and solid-state conformation as determined by the X-ray data. The data suggested that the solid-state and solution conformation of azaprophen were similar. The observed solid-state structure was also compared to low-energy conformations identified by molecular-mechanics calculations. A comparison of azaprophen and atropine radioligand binding in guinea pig ileum, rat heart, rat brain, and in CHO cells expressing transfected m1 and m3 receptors was conducted. Azaprophen is more active than atropine in all preparations except the m3 receptor expressed in CHO cells. However, like atropine, it does not provide major discrimination among the muscarinic receptor subtypes.


Electrical brain stimulation and continuous behavioral state tracking in ambulatory humans.
Objective.Electrical deep brain stimulation (DBS) is an established treatment for patients with drug-resistant epilepsy. Sleep disorders are common in people with epilepsy, and DBS may actually further disturb normal sleep patterns and sleep quality. Novel implantable devices capable of DBS and streaming of continuous intracranial electroencephalography (iEEG) signals enable detailed assessments of therapy efficacy and tracking of sleep related comorbidities. Here, we investigate the feasibility of automated sleep classification using continuous iEEG data recorded from Papez's circuit in four patients with drug resistant mesial temporal lobe epilepsy using an investigational implantable sensing and stimulation device with electrodes implanted in bilateral hippocampus (HPC) and anterior nucleus of thalamus (ANT).Approach.The iEEG recorded from HPC is used to classify sleep during concurrent DBS targeting ANT. Simultaneous polysomnography (PSG) and sensing from HPC were used to train, validate and test an automated classifier for a range of ANT DBS frequencies: no stimulation, 2 Hz, 7 Hz, and high frequency (>100 Hz).Main results.We show that it is possible to build a patient specific automated sleep staging classifier using power in band features extracted from one HPC iEEG sensing channel. The patient specific classifiers performed well under all thalamic DBS frequencies with an average F1-score 0.894, and provided viable classification into awake and major sleep categories, rapid eye movement (REM) and non-REM. We retrospectively analyzed classification performance with gold-standard PSG annotations, and then prospectively deployed the classifier on chronic continuous iEEG data spanning multiple months to characterize sleep patterns in ambulatory patients living in their home environment.Significance.The ability to continuously track behavioral state and fully characterize sleep should prove useful for optimizing DBS for epilepsy and associated sleep, cognitive and mood comorbidities.


Chronic ingestion of 2-deoxy-D-glucose induces cardiac vacuolization and increases mortality in rats.
Calorie restriction (CR), the purposeful reduction of energy intake with maintenance of adequate micronutrient intake, is well known to extend the lifespan of laboratory animals. Compounds like 2-deoxy-D-glucose (2DG) that can recapitulate the metabolic effects of CR are of great interest for their potential to extend lifespan. 2DG treatment has been shown to have potential therapeutic benefits for treating cancer and seizures. 2DG has also recapitulated some hallmarks of the CR phenotype including reduced body temperature and circulating insulin in short-term rodent trials, but one chronic feeding study in rats found toxic effects. The present studies were performed to further explore the long-term effects of 2DG in vivo. First we demonstrate that 2DG increases mortality of male Fischer-344 rats. Increased incidence of pheochromocytoma in the adrenal medulla was also noted in the 2DG treated rats. We reconfirm the cardiotoxicity of 2DG in a 6-week follow-up study evaluating male Brown Norway rats and a natural form of 2DG in addition to again examining effects in Fischer-344 rats and the original synthetic 2DG. High levels of both 2DG sources reduced weight gain secondary to reduced food intake in both strains. Histopathological analysis of the hearts revealed increasing vacuolization of cardiac myocytes with dose, and tissue staining revealed the vacuoles were free of both glycogen and lipid. We did, however, observe higher expression of both cathepsin D and LC3 in the hearts of 2DG-treated rats which indicates an increase in autophagic flux. Although a remarkable CR-like phenotype can be reproduced with 2DG treatment, the ultimate toxicity of 2DG seriously challenges 2DG as a potential CR mimetic in mammals and also raises concerns about other therapeutic applications of the compound.


Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain.
Lung adenocarcinomas from patients who respond to the tyrosine kinase inhibitors gefitinib (Iressa) or erlotinib (Tarceva) usually harbor somatic gain-of-function mutations in exons encoding the kinase domain of the epidermal growth factor receptor (EGFR). Despite initial responses, patients eventually progress by unknown mechanisms of "acquired" resistance. We show that in two of five patients with acquired resistance to gefitinib or erlotinib, progressing tumors contain, in addition to a primary drug-sensitive mutation in EGFR, a secondary mutation in exon 20, which leads to substitution of methionine for threonine at position 790 (T790M) in the kinase domain. Tumor cells from a sixth patient with a drug-sensitive EGFR mutation whose tumor progressed on adjuvant gefitinib after complete resection also contained the T790M mutation. This mutation was not detected in untreated tumor samples. Moreover, no tumors with acquired resistance had KRAS mutations, which have been associated with primary resistance to these drugs. Biochemical analyses of transfected cells and growth inhibition studies with lung cancer cell lines demonstrate that the T790M mutation confers resistance to EGFR mutants usually sensitive to either gefitinib or erlotinib. Interestingly, a mutation analogous to T790M has been observed in other kinases with acquired resistance to another kinase inhibitor, imatinib (Gleevec). In patients with tumors bearing gefitinib- or erlotinib-sensitive EGFR mutations, resistant subclones containing an additional EGFR mutation emerge in the presence of drug. This observation should help guide the search for more effective therapy against a specific subset of lung cancers.


Values in the care for young persons with Prader-Willi syndrome: creating a meaningful life together.
Caregivers sometimes feel frustrated by present emphasis on self-determination in the care for individuals with an intellectual disability. They are confronted with situations in which there is a conflict between providing high quality care and respecting the client's autonomy. Such conflicts are prominent in the care for people with Prader-Willi syndrome (PWS). This condition is characterized by overeating behaviour which frequently leads to serious obesity. The central question in the present study is how persons involved, parents and professional caregivers, deal with the problems of the prevention of obesity in young individuals with PWS in everyday life. In-depth qualitative interviews were conducted with 23 parents and 14 professional caregivers of 18 persons with PWS. The interview data were analysed using the constant comparative method as described in grounded theory. On the basis of analysis of the interviews four values emerge that parents and professional caregivers indicate as relevant and directive to their acting towards the child or the client: physical health, well-being, freedom and responsibility, and a liveable life. Furthermore, caregivers mentioned several enabling and limiting conditions that influence these values. And they named several interventions they used to realize the values. Of importance is the question how to create life in such a way that it is acceptable and meaningful for everybody involved. By building up a relationship to which acceptance and trust are central, a certain amount of independence and responsibility can be promoted. By creating trust it is possible to deal with rules in a less rigid way and to look where there is room for choices.


Influence of electronic type purity on the lithiation of single-walled carbon nanotubes.
Single-walled carbon nanotubes (SWCNTs) have emerged as one of the leading additives for high-capacity nanocomposite lithium ion battery electrodes due to their ability to improve electrode conductivity, current collection efficiency, and charge/discharge rate for high power applications. However, since as-grown SWCNTs possess a distribution of physical and electronic structures, it is of high interest to determine which subpopulations of SWCNTs possess the highest lithiation capacity and to develop processing methods that can enhance the lithiation capacity of underperforming SWCNT species. Toward this end, SWCNT electronic type purity is controlled via density gradient ultracentrifugation, enabling a systematic study of the lithiation of SWCNTs as a function of metal versus semiconducting content. Experimentally, vacuum-filtered freestanding films of metallic SWCNTs are found to accommodate lithium with an order of magnitude higher capacity than their semiconducting counterparts, which is consistent with ab initio molecular dynamics and density functional theory calculations in the limit of isolated SWCNTs. In contrast, SWCNT film densification leads to the enhancement of the lithiation capacity of semiconducting SWCNTs to levels comparable to metallic SWCNTs, which is corroborated by theoretical calculations that show increased lithiation of semiconducting SWCNTs in the limit of small SWCNT-SWCNT spacing. Overall, these results will inform ongoing efforts to utilize SWCNTs as conductive additives in nanocomposite lithium ion battery electrodes.


Lotus japonicus forms early senescent root nodules with Rhizobium etli.
Mesorhizobium loti and Rhizobium etli are microsymbionts of the Lotus and Phaseolus spp., respectively, and secrete essentially the same Nod factors. Lotus japonicus efficiently formed root nodules with R. etli CE3, irrespective of the presence or absence of a flavonoid-independent transcription activator nodD gene. On a nitrogen-free medium, however, the host plant inoculated with R. etli showed a severe nitrogen deficiency symptom. Initially, the nodules formed with R. etli were pale pink and leghemoglobin mRNA was detectable at significant levels. Nevertheless, the nodules became greenish with time. Acetylene-reduction activity of nodules formed with R. etli was comparable with that formed by M. loti 3 weeks postinoculation, but thereafter it decreased rapidly. The nodules formed with R. etli contained much more starch granules than those formed with M. loti. R. etli developed into bacteroids in the L. japonicus nodules, although the density of bacteroids in the infected cells was lower than that in the nodules formed with M. loti. The nodules formed with R. etli were of the early senescence type, in that membrane structures were drastically disintegrated in the infected cells of the greenish nodules. Thus, L. japonicus started and then ceased a symbiotic relationship with R. etli at the final stage.


Nanostructured Amphiphilic Star-Hyperbranched Block Copolymers for Drug Delivery.
A robust drug delivery system based on nanosized amphiphilic star-hyperbranched block copolymer, namely, poly(methyl methacrylate-block-poly(hydroxylethyl methacrylate) (PMMA-b-PHEMA) is described. PMMA-b-PHEMA was prepared by sequential visible light induced self-condensing vinyl polymerization (SCVP) and conventional vinyl polymerization. All of the synthesis and characterization details of the conjugates are reported. To accomplish tumor cell targeting property, initially cell-targeting (arginylglycylaspactic acid; RGD) and penetrating peptides (Cys-TAT) were binding to each other via the well-known EDC/NHS chemistry. Then, the resulting peptide was further incorporated to the surface of the amphiphilic hyperbranched copolymer via a coupling reaction between the thiol (-SH) group of the peptide and the hydroxyl group of copolymer by using N-(p-maleinimidophenyl) isocyanate as a heterolinker. The drug release property and targeting effect of the anticancer drug (doxorobucin; DOX) loaded nanostructures to two different cell lines were evaluated in vitro. U87 and MCF-7 were chosen as integrin αvβ3 receptor positive and negative cells for the comparison of the targeting efficiency, respectively. The data showed that drug-loaded copolymers exhibited enhanced cell inhibition toward U87 cells in compared to MCF-7 cells because targeting increased the cytotoxicity of drug-loaded copolymers against integrin αvβ3 receptor expressing tumor cells.


Disentangling the Role of Cortico-Basal Ganglia Loops in Top-Down and Bottom-Up Visual Attention: An Investigation of Attention Deficits in Parkinson Disease.
It is solidly established that top-down (goal-driven) and bottom-up (stimulus-driven) attention mechanisms depend on distributed cortical networks, including prefrontal and frontoparietal regions. On the other hand, it is less clear whether the BG also contribute to one or the other of these mechanisms, or to both. The current study was principally undertaken to clarify this issue. Parkinson disease (PD), a neurodegenerative disorder primarily affecting the BG, has proven to be an effective model for investigating the contribution of the BG to different brain functions; therefore, we set out to investigate deficits of top-down and bottom-up attention in a selected cohort of PD patients. With this objective in mind, we compared the performance on three computerized tasks of two groups of 12 parkinsonian patients (assessed without any treatment), one otherwise pharmacologically treated and the other also surgically treated, with that of a group of controls. The main behavioral tool for our study was an attentional capture task, which enabled us to tap the competition between top-down and bottom-up mechanisms of visual attention. This task was suitably combined with a choice RT and a simple RT task to isolate any specific deficit of attention from deficits in motor response selection and initiation. In the two groups of patients, we found an equivalent increase of attentional capture but also comparable delays in target selection in the absence of any salient distractor (reflecting impaired top-down mechanisms) and movement initiation compared with controls. In contrast, motor response selection processes appeared to be prolonged only in the operated patients. Our results confirm that the BG are involved in both motor and cognitive domains. Specifically, damage to the BG, as it occurs in PD, leads to a distinct deficit of top-down control of visual attention, and this can account, albeit indirectly, for the enhancement of attentional capture, reflecting weakened ability of top-down mechanisms to antagonize bottom-up control.


High diabetes prevalence among tuberculosis cases in Kerala, India.
While diabetes mellitus (DM) is a known risk factor for tuberculosis, the prevalence among TB patients in India is unknown. Routine screening of TB patients for DM may be an opportunity for its early diagnosis and improved management and might improve TB treatment outcomes. We conducted a cross-sectional survey of TB patients registered from June-July 2011 in the state of Kerala, India, to determine the prevalence of DM. A state-wide representative sample of TB patients in Kerala was interviewed and screened for DM using glycosylated hemoglobin (HbA1c); patients self-reporting a history of DM or those with HbA1c ≥6.5% were defined as diabetic. Among 552 TB patients screened, 243(44%) had DM - 128(23%) had previously known DM and 115(21%) were newly diagnosed - with higher prevalence among males and those aged >50 years. The number needed to screen(NNS) to find one newly diagnosed case of DM was just four. Of 128 TB patients with previously known DM, 107(84%) had HbA1c ≥7% indicating poor glycemic control. Nearly half of TB patients in Kerala have DM, and approximately half of these patients were newly-diagnosed during this survey. Routine screening of TB patients for DM using HbA1c yielded a large number of DM cases and offered earlier management opportunities which may improve TB and DM outcomes. However, the most cost-effective ways of DM screening need to be established by futher operational research.


Even moderate visual impairments degrade drivers' ability to see pedestrians at night.
To determine the effect of moderate levels of refractive blur and simulated cataracts on nighttime pedestrian conspicuity in the presence and absence of headlamp glare. The ability to recognize pedestrians at night was measured in 28 young adults (M = 27.6 years) under three visual conditions: normal vision, refractive blur, and simulated cataracts; mean acuity was 20/40 or better in all conditions. Pedestrian recognition distances were recorded while participants drove an instrumented vehicle along a closed road course at night. Pedestrians wore one of three clothing conditions and oncoming headlamps were present for 16 participants and absent for 12 participants. Simulated visual impairment and glare significantly reduced the frequency with which drivers recognized pedestrians and the distance at which the drivers first recognized them. Simulated cataracts were significantly more disruptive than blur even though photopic visual acuity levels were matched. With normal vision, drivers responded to pedestrians at 3.6- and 5.5-fold longer distances on average than for the blur or cataract conditions, respectively. Even in the presence of visual impairment and glare, pedestrians were recognized more often and at longer distances when they wore a "biological motion" reflective clothing configuration than when they wore a reflective vest or black clothing. Drivers' ability to recognize pedestrians at night is degraded by common visual impairments, even when the drivers' mean visual acuity meets licensing requirements. To maximize drivers' ability to see pedestrians, drivers should wear their optimum optical correction, and cataract surgery should be performed early enough to avoid potentially dangerous reductions in visual performance.


Molecular analysis of two local falciparum malaria outbreaks on the French Guiana coast confirms the msp1 B-K1/varD genotype association with severe malaria.
Plasmodium falciparum outbreaks can occur in the coastal area of French Guiana, where the population is essentially non-immune. Two sporadic outbreaks were observed, including one with severe malaria cases. To characterize these outbreaks and verify previous observations of specific genotype characteristics in severe malaria in this area, all cases from each outbreak were studied. P. falciparum genotypes for six genetic loci were determined by PCR amplification from peripheral blood parasites. The msp1/block2 and msp2 genotypes were determined by DNA sequencing. Microsatellite and varD genotyping was based on size polymorphism and locus-specific amplification. The outbreak including severe malaria cases was associated with a single genotype. The other mild malaria outbreak was due to at least five distinct genotypes. Two distinct types of outbreak occurred despite systematic and sustained deployment of malaria control measures, indicating a need for reinforced vigilance. The varD/B-K1 msp1 linkage and its association with severe malaria in this area was confirmed.


Clinical trial of microcrystalline hydroxyapatite compound ('Ossopan') in the prevention of osteoporosis due to corticosteroid therapy.
A controlled clinical trial was carried out in 40 patients at risk of osteoporosis because of long-term treatment with prednisolone (5 to 20 mg/day) to determine the efficacy and tolerance of microcrystalline hydroxyapatite compound (MCHC) when used to prevent the appearance or progression of osteoporosis: 32 patients were treated with 6 to 8 g MCHC for 12 months and 8 served as an untreated control group. The two groups were well matched as regards age, sex and underlying disease; 37 patients (29 MCHC, 8 control) successfully completed the trial. The majority (68%) of the patients had back pain prior to the trial, the severity of which was graded at 3-monthly intervals. In the MCHC-treated group, there was a dramatic and significant (p less than 0.001) reduction in pain during the trial, almost to the point of its disappearance. Of 19 patients with initial back pain only 2 still reported any pain at all after 12-months' MCHC treatment. In the control group, back pain severity increased during the trial in 3 patients and was unchanged in the fourth. Neither MCHC-treated nor control group patients showed any significant change in standing or stem height during the 12-months' trial period. Both mean cortical thickness and mean metacarpal index figures showed small, insignificant decreases during 12-months' MCHC treatment but much more marked decreases in the control group which, despite the small number of patients, came close to being statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)


Twinning in metastable high-entropy alloys.
Twinning is a fundamental mechanism behind the simultaneous increase of strength and ductility in medium- and high-entropy alloys, but its operation is not yet well understood, which limits their exploitation. Since many high-entropy alloys showing outstanding mechanical properties are actually thermodynamically unstable at ambient and cryogenic conditions, the observed twinning challenges the existing phenomenological and theoretical plasticity models. Here, we adopt a transparent approach based on effective energy barriers in combination with first-principle calculations to shed light on the origin of twinning in high-entropy alloys. We demonstrate that twinning can be the primary deformation mode in metastable face-centered cubic alloys with a fraction that surpasses the previously established upper limit. The present advance in plasticity of metals opens opportunities for tailoring the mechanical response in engineering materials by optimizing metastable twinning in high-entropy alloys.


Dynamic Consent: a potential solution to some of the challenges of modern biomedical research.
Innovations in technology have contributed to rapid changes in the way that modern biomedical research is carried out. Researchers are increasingly required to endorse adaptive and flexible approaches to accommodate these innovations and comply with ethical, legal and regulatory requirements. This paper explores how Dynamic Consent may provide solutions to address challenges encountered when researchers invite individuals to participate in research and follow them up over time in a continuously changing environment. An interdisciplinary workshop jointly organised by the University of Oxford and the COST Action CHIP ME gathered clinicians, researchers, ethicists, lawyers, research participants and patient representatives to discuss experiences of using Dynamic Consent, and how such use may facilitate the conduct of specific research tasks. The data collected during the workshop were analysed using a content analysis approach. Dynamic Consent can provide practical, sustainable and future-proof solutions to challenges related to participant recruitment, the attainment of informed consent, participant retention and consent management, and may bring economic efficiencies. Dynamic Consent offers opportunities for ongoing communication between researchers and research participants that can positively impact research. Dynamic Consent supports inter-sector, cross-border approaches and large scale data-sharing. Whilst it is relatively easy to set up and maintain, its implementation will require that researchers re-consider their relationship with research participants and adopt new procedures.


The role of augmentative and alternative communication for children with autism: current status and future trends.
Augmentative and alternative communication (AAC) interventions are used for children with autism, often as stand-alone communication interventions for those who are minimally verbal. Our aim was to synthesize the evidence for AAC interventions for children (up to 21 years), and then consider the role of AAC within established, comprehensive, evidence-based autism interventions targeting learning across multiple developmental domains. We completed a systematic search of three databases (OVID Medline, PsycINFO, ERIC) as well as forward citation and hand searches to identify systematic reviews of AAC intervention efficacy research including children with autism, published between 2000 and March 2016 in peer-reviewed journals. Data pertaining to the quality indicators of included studies, effect sizes for intervention outcomes, and evidence for effectiveness were extracted for descriptive analysis. The search yielded 17 systematic reviews. Most provided indicators of research quality for included studies, of which only relatively few provided conclusive results. Communication targets tended to be focused on teaching children to make requests. Still, effect size measures for included studies indicated that AAC was effective to highly effective. There is growing evidence for the potential benefits of AAC for children with autism, but there is a need for more well-designed studies and broader, targeted outcomes. Furthermore, a lack of evidence for the role of AAC within comprehensive intervention programs may account for a tendency by autism researchers and practitioners to neglect this intervention. Attempts to compare evidence for AAC with other interventions for children with autism, including those in which the use of AAC is delayed or excluded in pursuit of speech-only communication, must take into account the needs of children with the most significant learning needs. These children pose the greatest challenges to achieving large and consistent intervention effects, yet stand to gain the most from AAC interventions.


Rapid intrapartum or postpartum HIV testing at a midwife obstetric unit and a district hospital in South Africa.
To compare the prepartum and postpartum feasibility and acceptance of voluntary counseling and rapid testing (VCT) among women with unknown HIV status in South Africa. Eligible women were randomized according to the calendar week of presentation to receive VCT either while in labor or after delivery. Of 7238 women approached, 542 (7.5%) were eligible, 343 (63%) were enrolled, and 45 (13%) were found to be HIV infected. The proportions of eligible women who accepted VCT were 66.8% (161 of 241) in the intrapartum arm and 60.5% (182 of 301) in the postpartum arm, and the difference of 6.3% (95% CI, -1.8% to 14.5%) was not significant. The median times (44 and 45 minutes) required to conduct VCT were also similar in the 2 arms. In the intrapartum arm, all women in true labor received their test results before delivery and all those found to be HIV positive accepted prophylaxis with nevirapine before delivery. Rapid testing in labor wards for women with an unknown HIV status is feasible and well accepted, and allows for a more timely antiretroviral prophylaxis than postpartum testing.


Pomalidomide Ameliorates H₂O₂-Induced Oxidative Stress Injury and Cell Death in Rat Primary Cortical Neuronal Cultures by Inducing Anti-Oxidative and Anti-Apoptosis Effects.
Due to its high oxygen demand and abundance of peroxidation-susceptible lipid cells, the brain is particularly vulnerable to oxidative stress. Induced by a redox state imbalance involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system, oxidative stress plays a central role in a common pathophysiology that underpins neuronal cell death in acute neurological disorders epitomized by stroke and chronic ones such as Alzheimer's disease. After cerebral ischemia, for example, inflammation bears a key responsibility in the development of permanent neurological damage. ROS are involved in the mechanism of post-ischemic inflammation. The activation of several inflammatory enzymes produces ROS, which subsequently suppress mitochondrial activity, leading to further tissue damage. Pomalidomide (POM) is a clinically available immunomodulatory and anti-inflammatory agent. Using H₂O₂-treated rat primary cortical neuronal cultures, we found POM displayed neuroprotective effects against oxidative stress and cell death that associated with changes in the nuclear factor erythroid derived 2/superoxide dismutase 2/catalase signaling pathway. POM also suppressed nuclear factor kappa-light-chain-enhancer (NF-κB) levels and significantly mitigated cortical neuronal apoptosis by regulating Bax, Cytochrome c and Poly (ADP-ribose) polymerase. In summary, POM exerted neuroprotective effects via its anti-oxidative and anti-inflammatory actions against H₂O₂-induced injury. POM consequently represents a potential therapeutic agent against brain damage and related disorders and warrants further evaluation.


The impact of the COSHH regulations on workers with occupational asthma.
In the UK, the COSHH Regulations give specific guidance that employers have duties to inform, instruct and train their employees about occupational risks and provide them with suitable health surveillance. The aim of the study was to evaluate the impact of the Regulations on employees with occupational asthma. One hundred consecutive patients attending an occupational lung disease clinic completed a questionnaire assessing the implementation of the COSHH Regulations in their workplace. Twenty-eight per cent had a pre-employment inquiry about asthma, 31% had regular health surveillance by questionnaires and 19% had regular lung function assessment at work. Pre-employment spirometry was carried out in 44% of the workers who were exposed to one of the original seven prescribed agents, significantly more than those who were exposed to other agents (19%) (p < 0.05). Moreover, figures for spirometry during employment were 31% and 8% respectively (p < 0.05). The patients who worked after 'COSHH' but before 'MS25' had a tendency to be provided with health surveillance more than those who worked after both 'COSHH' and 'MS25'. Ninety-one per cent of the patients had never been informed about the risks of getting asthma at work and 73% had never seen the safety data sheets. The workers who (1) worked after 'COSHH' introduction; (2) worked in larger firms and (3) were exposed to one of the original seven prescribed' agents, had a tendency to be informed, instructed and trained more than the rest. However, there were only significant statistical differences (p < 0.05) in terms of the safety data sheet position between the cases who worked before the time of the legislation and those employed afterwards.


Uranium-thorium-lead isotope relations in lunar materials.
The lead isotopic compositions and uranium, thorium, and lead concentrations have been measured on six samples of material from the Sea of Tranquillity. The leads are moderately to very radiogenic; the initial lead concentrations are very low; the uranium and thorium levels are 0.26 to 0.88 and 0.87 to 3.35 parts per million, respectively. The Th/U ratios cluster about a 3.6 value. Apparent ages calculated for four rocks are 4.1 to 4.2 x 10(9) years. Dust and breccia yield apparent ages of 4.60 to 4.63 x 10(9) years. The uranium-lead ages are concordant, or nearly so, in all cases. The lunar surface is an ancient region with an extended record of events in the early history of the solar system. discrepancy between the rock ages and dust ages poses a fundamental qusestion about rock genesis on the moon.


The geographic distribution of onchocerciasis in the 20 participating countries of the African Programme for Onchocerciasis Control: (2) pre-control endemicity levels and estimated number infected.
The original aim of the African Programme for Onchocerciasis Control (APOC) was to control onchocerciasis as a public health problem in 20 African countries. In order to identify all high risk areas where ivermectin treatment was needed to achieve control, APOC used Rapid Epidemiological Mapping of Onchocerciasis (REMO). REMO involved spatial sampling of villages to be surveyed, and examination of 30 to 50 adults per village for palpable onchocercal nodules. REMO has now been virtually completed and we report the results in two articles. A companion article reports the delineation of high risk areas based on expert analysis. The present article reports the results of a geostatistical analysis of the REMO data to map endemicity levels and estimate the number infected. A model-based geostatistical analysis of the REMO data was undertaken to generate high-resolution maps of the predicted prevalence of nodules and of the probability that the true nodule prevalence exceeds the high risk threshold of 20%. The number infected was estimated by converting nodule prevalence to microfilaria prevalence, and multiplying the predicted prevalence for each location with local data on population density. The geostatistical analysis included the nodule palpation data for 14,473 surveyed villages. The generated map of onchocerciasis endemicity levels, as reflected in the prevalence of nodules, is a significant advance with many new endemic areas identified. The prevalence of nodules was > 20% over an area of 2.5 million km2 with an estimated population of 62 million people. The results were consistent with the delineation of high risk areas of the expert analysis except for borderline areas where the prevalence fluctuated around 20%. It is estimated that 36 million people would have been infected in the APOC countries by 2011 if there had been no ivermectin treatment. The map of onchocerciasis endemicity levels has proven very valuable for onchocerciasis control in the APOC countries. Following the recent shift to onchocerciasis elimination, the map continues to play an important role in planning treatment, evaluating impact and predicting treatment end dates in relation to local endemicity levels.


Forensic psychiatric assessment process and outcome in state patients in KwaZulu-Natal, South Africa.
Individuals who were charged with a serious offence may be referred by courts for forensic psychiatric assessment. The court may declare them as state patients if they are found unfit to stand trial or not criminally responsible because of mental illness or defect.In forensic psychiatry practice, there may be challenges in the forensic psychiatric observation process, and discrepancies may occur between the clinician report and the court's decision. To describe elements of the forensic psychiatric observation and discuss the legal correlates associated with the admission of state patients. A retrospective study of the forensic psychiatric observation records of 91 newly admitted state patients at a forensic unit in KwaZulu-Natal over a 3-year period. A total of 71 state patients (78.02%) were found not fit to stand trial and 10 patients (10.99%) were not criminally responsible. Nine patients (9.89%) were fit to stand trial and criminally responsible but still declared state patients and 13 state patients (14.29%) did not commit a serious offence. There was correlation for diagnosis between the assessing and the treating psychiatrists. The findings of the forensic observation were not always considered by the courts. Individuals found fit to stand trial, those found criminally responsible and those who did not commit serious crimes were declared state patients.A better understanding of legal dispositions for mentally ill offenders and an active collaboration between judicial and mental health systems may contribute in developing national guidelines for observation and admission of state patients.


Trends in smoking by age and sex, United States, 1974-1987: the implications for disease impact.
Using data from the 1974-1987 National Health Interview Surveys, we report trends in current smoking prevalence and quit ratios (the proportion of those who have ever smoked who no longer smoke) for men and women in the age groups 20-24, 25-44, 45-64, and 65 years and older. Current smoking prevalence decreased linearly for men in all age subgroups except 65 and older and for women ages 25-44 and 45-64 years only. The quit ratios increased linearly within each age/sex subgroup except for men and women ages 20-24 years. Overall, there were about 1.4 million fewer male smokers and over 1 million more female smokers in 1987 than there were in 1974. Between 1974 and 1987, the population ages 25-44 years increased by approximately 47%, and the population 65 years and older increased by approximately 34%. As a result, between 1974 and 1987, the actual number of smokers increased among men ages 25-44 years (8% increase), women ages 25-44 years (15% increase), and women ages 65 years and older (50% increase). These data suggest that even with favorable recent changes in the overall smoking prevalence of the U.S. population, the disease impact of smoking will increase for decades, especially among women. This scenario will be mitigated if increased attention is given to cessation among women in general and to the post-World War II generation of both male and female smokers.


Long-term follow-up of schizophrenia in 16 countries. A description of the International Study of Schizophrenia conducted by the World Health Organization.
An unexpected finding of the International Pilot Study of Schizophrenia, launched by the World Health Organization (WHO) in 1967, was that patients in countries outside Europe and the United States have a more favourable short- and medium-term course of the disease than those seen in developed countries. Since then, WHO has intensified its schizophrenia research programme and has initiated a set of international studies that have confirmed these initial findings and explored possible reasons for such differences in the course and outcome of schizophrenia. While such work has provided important findings and has generated additional pertinent hypotheses, it did not explain the differences in outcome. The present paper describes a new initiative in which approximately 2500 subjects involved in previous WHO multicentre schizophrenia studies are being followed up for between 15 and 25 years after initial examination. Nineteen research centres in 16 countries are taking part in this work. The research methodology is described.


Reduction of Campylobacter jejuni on chicken wings by chemical treatments.
Eight chemicals, including glycerol monolaurate, hydrogen peroxide, acetic acid, lactic acid, sodium benzoate, sodium chlorate, sodium carbonate, and sodium hydroxide, were tested individually or in combination for their ability to inactivate Campylobacter jejuni at 4 degrees C in suspension. Results showed that treatment for up to 20 min with 0.01% glycerol monolaurate, 0.1% sodium benzoate, 50 or 100 mM sodium chlorate, or 1% lactic acid did not substantially (< or = 0.5 log CFU/ml) reduce C. jejuni populations but that 0.1 and 0.2% hydrogen peroxide for 20 min reduced C. jejuni populations by ca. 2.0 and 4.5 log CFU/ml, respectively. By contrast, treatments with 0.5, 1.0, 1.5, and 2.0% acetic acid, 25, 50, and 100 mM sodium carbonate, and 0.05 and 0.1 N sodium hydroxide reduced C. jejuni populations by >5 log CFU/ml within 2 min. A combination of 0.5% acetic acid plus 0.05% potassium sorbate or 0.5% acetic acid plus 0.05% sodium benzoate reduced C. jejuni populations by >5 log CFU/ml within 1 min; however, substituting 0.5% lactic acid for 0.5% acetic acid was not effective, with a reduction of C. jejuni of <0.5 log CFU/ml. A combination of acidic calcium sulfate, lactic acid, ethanol, sodium dodecyl sulfate, and polypropylene glycol (ACS-LA) also reduced C. jejuni in suspension by >5 log CFU/ml within 1 min. All chemicals or chemical combinations for which there was a >5-log/ml reduction of C. jejuni in suspension were further evaluated for C. jejuni inactivation on chicken wings. Treatments at 4 degrees C of 2% acetic acid, 100 mM sodium carbonate, or 0.1 N sodium hydroxide for up to 45 s reduced C. jejuni populations by ca. 1.4, 1.6, or 3.5 log CFU/g, respectively. Treatment with ACS-LA at 4 degrees C for 15 s reduced C. jejuni by >5 log CFU/g to an undetectable level. The ACS-LA treatment was highly effective in chilled water at killing C. jejuni on chicken and, if recycled, may be a useful treatment in chill water tanks for poultry processors to reduce campylobacters on poultry skin after slaughter.


[Blueberry anthocyanins induce G2/M cell cycle arrest and apoptosis of oral cancer KB cells through down-regulation methylation of p53].
Blueberries are an excellent source of dietary polyphenols such as anthocyanins and phenolic acids. In this study, we investigated the ability of anthocyanins from the wild blueberries of Inner Mongolia to suppress the growth of the oral cancer cell line KB. The blueberry anthocyanins were extracted with methanol-containing 0.1% (v/v) hydrochloric acid. Fourteen unique anthocyanins were identified using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The anticancer bioactivity of the extracts on KB cells was analyzed using methylthiazolyl-tetrazolium (MTT), flow cytometry (FCM) and immunocytochemistry. It was shown that the blueberry anthocyanins suppressed the proliferation of KB cells in a dose-dependent manner, as well as induced G2/M cell cycle arrest and apoptosis of oral cancer KB cells. Immunocytochemistry analysis showed that the expression of caspase-9 and cytochrome c were obviously increased after the anthocyanins treatment. Western blot analysis also indicated that the expression of p53 was increased. Methylation-specific PCR (MSP) showed that the amount of unmethylated p53 increased, indicating that the anthocyanins can down-regulate the methylation of p53.


Cell-Permeable Oct4 Gene Delivery Enhances Stem Cell-like Properties of Mouse Embryonic Fibroblasts.
Direct conversion of one cell type into another is a trans-differentiation process. Recent advances in fibroblast research revealed that epithelial cells can give rise to fibroblasts by epithelial-mesenchymal transition. Conversely, fibroblasts can also give rise to epithelia by undergoing a mesenchymal to epithelial transition. To elicit stem cell-like properties in fibroblasts, the Oct4 transcription factor acts as a master transcriptional regulator for reprogramming somatic cells. Notably, the production of gene complexes with cell-permeable peptides, such as low-molecular-weight protamine (LMWP), was proposed to induce reprogramming without cytotoxicity and genomic mutation. We designed a complex with non-cytotoxic LMWP to prevent the degradation of Oct4 and revealed that the positively charged cell-permeable LMWP helped condense the size of the Oct4-LMWP complexes (1:5 N:P ratio). When the Oct4-LMWP complex was delivered into mouse embryonic fibroblasts (MEFs), stemness-related gene expression increased while fibroblast intrinsic properties decreased. We believe that the Oct4-LMWP complex developed in this study can be used to reprogram terminally differentiated somatic cells or convert them into stem cell-like cells without risk of cell death, improving the stemness level and stability of existing direct conversion techniques.


Contemporary management of spinal AVFs and AVMs: lessons learned from 110 cases.
Spinal arteriovenous fistulas (AVFs) and arteriovenous malformations (AVMs) are rare, complex spinal vascular lesions that are challenging to manage. Recently, understanding of these lesions has increased thanks to neuroimaging technology. Published reports of surgical results and clinical outcome are limited to small series. The authors present a large contemporary series of patients with spinal AVFs and AVMs who were treated at Barrow Neurological Institute in Phoenix, Arizona. Retrospective detailed review of a prospective vascular database was performed for all patients with spinal AVFs and AVMs treated between 2000 and 2013. Patient demographic data, AVF and AVM characteristics, surgical results, clinical outcomes, complications, and long-term follow-up were reviewed. Between 2000 and 2013, 110 patients (57 male and 53 female) underwent obliteration of spinal AVFs and AVMs. The mean age at presentation was 42.3 years (range 18 months-81 years). There were 44 patients with AVFs and 66 with AVMs. The AVM group included 27 intramedullary, 21 conus medullaris, 12 metameric, and 6 extradural. The most common location was thoracic spine (61%), followed by cervical (22.7%), lumbar (14.5%), and sacral (1.8%). The most common presenting signs and symptoms included paresis/paralysis (75.5%), paresthesias (60%), pain (51.8%), bowel/bladder dysfunction (41.8%), and myelopathy (36.4%). Evidence of rupture was seen in 26.4% of patients. Perioperative embolization was performed in 42% of patients. Resection was performed in 95 patients (86.4%). Embolization alone was the only treatment in 14 patients (12.7%). One patient was treated with radiosurgery alone. Angiographically verified AVF and AVM obliteration was achieved in 92 patients (83.6%). At a mean follow-up duration of 30.5 months (range 1-205 months), 43 patients (97.7%) with AVFs and 57 (86.4%) with AVMs remained functionally independent (McCormick Scale scores ≤ 2). Perioperative complications were seen in 8 patients (7%). No deaths occurred. Temporary neurological deficits were observed in 27 patients (24.5%). These temporary deficits recovered 6-8 weeks after treatment. Recurrence was identified in 6 patients (13.6%) with AVFs and 10 (15.2%) with AVMs. Spinal AVFs and AVMs are complex lesions that should be considered for surgical obliteration. Over the last several decades the authors have changed surgical strategies and management to achieve better clinical outcomes. Transient neurological deficit postoperatively is a risk associated with intervention; however, clinical outcomes appear to exceed the natural history based on patients' ability to recover during the follow-up period. Due to the recurrence rate associated with these lesions, long-term follow-up is required.


Assessing the clinical significance of treatment outcomes for distressing voices in routine clinical practice.
Determining reliable and clinically significant change is central to evidence-based practice yet rarely used in routine clinical settings. This paper illustrates these methods in the context of an evaluation of cognitive behaviour therapy for distressing auditory hallucinations ("voices"). We used data from a clinical sample attending Perth Voices Clinic, a transdiagnostic outpatient service for distressing voices, and a previously published reference sample of healthy voice hearers. Our outcomes on the primary measure of voice distress, derived from a previous factor analysis of the Psychotic Symptom Rating Scale-Auditory Hallucinations subscale, showed that 62.9% of clients were classified as Recovered/Improved, 35.5% were classified as Unchanged, and 0.02% were classified as Deteriorated. Partial support for the validity of these classifications was obtained from the scores on the Depression, Anxiety, Stress Scales (Lovibond & Lovibond, 1995) but not on the Social and Occupational Functional Assessment Scale (Goldman et al., 1992). Clients classified as Recovered showed better emotional functioning on the Depression, Anxiety, Stress Scales compared with those who did not make a clinically significant change in voice distress. A tool is provided to assist practitioners to evaluate whether individual clients have benefited from therapy for distressing voices or not, which can be used to guide future treatment decisions (https://osf.io/gd9e5/).


Subsequent Total Joint Arthroplasty After Primary Total Knee or Hip Arthroplasty: A 40-Year Population-Based Study.
Despite the large increase in total hip arthroplasties and total knee arthroplasties, the incidence and prevalence of additional contralateral or ipsilateral joint arthroplasty are poorly understood. The purpose of this study was to determine the rate of additional joint arthroplasty after a primary total hip arthroplasty or total knee arthroplasty. This historical cohort study identified population-based cohorts of patients who underwent primary total hip arthroplasty (n = 1,933) or total knee arthroplasty (n = 2,139) between 1969 and 2008. Patients underwent passive follow-up through their medical records beginning with the primary total hip arthroplasty or total knee arthroplasty. We assessed the likelihood of undergoing a subsequent total joint arthroplasty, including simultaneous and staged bilateral procedures. Age, sex, and calendar year were evaluated as potential predictors of subsequent arthroplasty. During a mean follow-up of 12 years after an initial total hip arthroplasty, we observed 422 contralateral total hip arthroplasties (29% at 20 years), 76 contralateral total knee arthroplasties (6% at 10 years), and 32 ipsilateral total knee arthroplasties (2% at 20 years). Younger age was a significant predictor of contralateral total hip arthroplasty (p < 0.0001), but not a predictor of the subsequent risk of total knee arthroplasty. During a mean follow-up of 11 years after an initial total knee arthroplasty, we observed 809 contralateral total knee arthroplasties (45% at 20 years), 31 contralateral total hip arthroplasties (3% at 20 years), and 29 ipsilateral total hip arthroplasties (2% at 20 years). Older age was a significant predictor of ipsilateral or contralateral total hip arthroplasty (p < 0.001). Patients undergoing total hip arthroplasty or total knee arthroplasty can be informed of a 30% to 45% chance of a surgical procedure in a contralateral cognate joint and about a 5% chance of a surgical procedure in noncognate joints within 20 years of initial arthroplasty. Increased risk of contralateral total knee arthroplasty following an initial total hip arthroplasty may be due to gait changes prior to and/or following total hip arthroplasty. The higher prevalence of bilateral total hip arthroplasty in younger patients may result from bilateral disease processes that selectively affect the young hip, such as osteonecrosis, or structural hip problems, such as acetabular dysplasia or femoroacetabular impingement. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Exacerbation of sickle cell disease by obstructive sleep apnea.
It is difficult to recognize and treat the factors that exacerbate the vascular crises of sickle cell disease. We describe a 12-year-old black girl with sickle cell anemia who, since the age of 9 years, has been repeatedly hospitalized for pain associated with vaso-occlusive disease. A diagnosis of obstructive sleep apnea was suggested by the history and physical examination and was confirmed by polysomnography. Following preoperative transfusion, the patient underwent elective tonsillectomy and adenoidectomy. She has been free of vaso-occlusive pain and crises for over two years and has not been hospitalized since her surgery. Post-operative polysomnography has shown no evidence of obstructive sleep apnea. It is our hypothesis that repeated oxygen desaturation during periods of obstructive sleep apnea was the cause of this patient's frequent vaso-occlusive crises. She not only obtained complete relief of her symptoms, but objective sleep study measurements were normal following surgery. Obstructive sleep apnea is a recent diagnosis, and its pathologic effects are only beginning to be known. Physicians taking care of patients with hemoglobinopathies need to be aware of possible contributing factors to their patients' disease, and an aggressive approach to their diagnosis and possible relief should be sought.


Injuries associated with bottles, pacifiers, and sippy cups in the United States, 1991-2010.
To describe the epidemiology of injuries related to bottles, pacifiers, and sippy cups among young children in the United States. A retrospective analysis was conducted by using data from the National Electronic Injury Surveillance System for children <3 years of age treated in emergency departments (1991-2010) for an injury associated with a bottle, pacifier, or sippy cup. An estimated 45398 (95% confidence interval: 38 770-52 026) children aged <3 years were treated in emergency departments for injuries related to these products during the study period, an average of 2270 cases per year. Most injuries involved bottles (65.8%), followed by pacifiers (19.9%) and sippy cups (14.3%). The most common mechanism was a fall while using the product (86.1% of injuries). Lacerations comprised the most common diagnosis (70.4%), and the most frequently injured body region was the mouth (71.0%). One-year-old children were injured most often. Children who were aged 1 or 2 years were nearly 2.99 times (95% confidence interval: 2.07-4.33) more likely to sustain a laceration compared with any other diagnosis. Product malfunctions were relatively uncommon (4.4% of cases). This study is the first to use a nationally representative sample to examine injuries associated with these products. Given the number of injuries, particularly those associated with falls while using the product, greater efforts are needed to promote proper usage, ensure safety in product design, and increase awareness of American Academy of Pediatrics' recommendations for transitioning to a cup and discontinuing pacifier use.


Urodynamic risk factors for renal dysfunction in men with obstructive and nonobstructive voiding dysfunction.
Urodynamic investigation of men with lower urinary tract symptoms, usually attributed to benign prostatic hyperplasia, often reveals bladder outlet obstruction, detrusor instability and/or diminished vesical compliance. We investigated whether these urodynamic abnormalities alone or in combination contribute to renal dysfunction. A total of 161 men with lower urinary tract symptoms was evaluated by urodynamics, and outlet obstruction, detrusor instability and decreased compliance (30 ml./cm. water or less) were noted. Serum blood urea nitrogen (BUN) and creatinine were measured. Cases were categorized according to the urodynamic diagnosis. Mean values of serum BUN and creatinine as well as the incidence of elevated BUN and creatinine were compared among groups. Of the cohort 54 men (34%) had elevated BUN and 19 (12%) had elevated serum creatinine. No significant correlation was found between the degree of obstruction and BUN or creatinine level. Mean serum BUN and creatinine, and the incidence of abnormal laboratory tests did not significantly differ among those with outlet obstruction, detrusor instability, both conditions or neither condition. However, in patients with outlet obstruction and detrusor instability there was a significantly increased incidence of azotemia in the subgroup with diminished compliance (78%) versus the subgroup with normal compliance (36%). In men with voiding dysfunction of a nonneurogenic etiology outlet obstruction with or without detrusor instability does not appear to be a risk factor for elevated BUN and creatinine. However, when decreased bladder compliance is associated with a combination of outlet obstruction and detrusor instability, this risk is substantially increased.


Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations.
In a prospective, multicentre, double-blind controlled study, the effect of an intramuscular vitamin supplement containing 1 mg vitamin B12, 1.1 mg folate, and 5 mg vitamin B6 on serum concentrations of methylmalonic acid (MMA), homocysteine (HCYS), 2-methylcitric acid (2-MCA), and cystathionine (CYSTA) was compared with that of placebo in 175 elderly subjects living at home and 110 in hospital. Vitamin supplement and placebo were administered eight times over a 3-week period. Vitamin supplement but not placebo significantly reduced all four metabolite concentrations at the end of the study in both study groups. The maximum effects of treatment were usually seen within 5-12 days. Initially elevated metabolite concentrations returned to normal in a higher proportion of the vitamin than of the placebo group: 92% vs 20% for HYCS; 82% vs 20% for MMA; 62% vs 25% for 2-MCA; and 42% vs 25% for CYSTA. The response rate to vitamin supplements supports the notion that metabolic evidence of vitamin deficiency is common in the elderly, even in the presence of normal serum vitamin levels. Metabolite assays permit identification of elderly subjects who may benefit from vitamin supplements.


Visualization of the human enteric nervous system by confocal laser endomicroscopy in Hirschsprung's disease: An alternative to intraoperative histopathological diagnosis?
Hirschsprung's disease is a congenital abnormality of the enteric nervous system (ENS) presenting severe constipation soon after birth due to the lack of ganglion cells in the distal gut. Surgery for Hirschsprung's disease requires an intraoperative histopathological diagnosis to assess the extent of aganglionosis. Confocal laser endomicroscopy (CLE) is a novel endoscopic technique allowing real-time, in vivo analysis of cellular details during ongoing endoscopy. In this study, we evaluated the possibility of a new application of CLE to provide real-time observations of the ENS in patients with Hirschsprung's disease. In this preclinical feasibility study, we assessed the visualization of the ENS by CLE using surgically resected intestines. The subjects were nine patients who underwent pull-through surgery for Hirschsprung's disease between September 2014 and March 2016. The colon specimens were stained with 0.1% cresyl violet and evaluated using CLE. We compared the CLE findings with those of the histopathological examination. The ENS was clearly visualized as a ladder-like structure in the ganglionic segment but was not observed in the aganglionic segment. Of the 69 samples, corresponding positive and negative results for both CLE and the histopathology were obtained in 61 (88%). In addition, CLE was able to visualize unique, wavy structures comprising thick nerve bundles characteristic of the aganglionic/transition zone in Hirschsprung's disease. As a novel tool for visualizing the human ENS, CLE has the potential to revolutionize how pediatric surgeons identify the level of ganglionosis during surgery for Hirschsprung's disease and may be a superior alternative to intraoperative histopathological diagnosis.


The development of a training course for clubfoot treatment in Africa: learning points for course development.
Clubfoot is a common congenital musculoskeletal disorder that causes mobility impairment. There is a lack of trained mid-level personnel to provide clubfoot treatment in Africa and there is no standard training course. This prospective study describes the collaborative and participatory approach to the development of a training course for the treatment of clubfoot in children in resource constrained settings. We used a systems approach to evaluate the development of the training course. Inputs: The research strategy included a review of context and available training materials, and the collection of data on current training practices. Semi-structured interviews were conducted with seven expert clubfoot trainers. A survey of 32 international and regional trainers was undertaken to inform practical issues. The data were used to develop a framework for training with advice from two technical groups, consisting of regional and international stakeholders and experts. A consensus approach was undertaken during workshops, meetings and the sharing of documents. The design process for the training materials took twenty-four months and was iterative. The training materials were piloted nine times between September 2015 and February 2017. Processes and materials were reviewed and adapted according to feedback after each pilot. Fifty-one regional trainers from Africa (18 countries), 21 international experts (11 countries), 113 local providers of clubfoot treatment (Ethiopia, Rwanda and Kenya) and local organising teams were involved in developing the curriculum and pilot testing. The diversity of the two technical advisory groups allowed a wide range of contributions to the collaboration. Output: The resulting curriculum and content comprised a two day basic training and a two day advanced course. The basic course utilised adult learning techniques for training novice providers in the treatment of idiopathic clubfoot in children under two years old. The advanced course builds on these principles. Formative research that included mixed methods (both qualitative and quantitative) was important in the development of an appropriate training course. The process documentation from this study provides useful information to assist planning of medical training programmes and may serve as a model for the development of other courses.


Novel knowledge-based mean force potential at atomic level.
We present a new approach at the atomic level for the development of knowledge-based mean force potentials (MFPs) that can be used in fold recognition, ab initio structure prediction, comparative modelling and molecular recognition. Our method is based on atom-type definitions, raising the total frequency of the pairwise distributions and leading to very accurate and specific distance-dependent energy functions. Forty different heavy atom types were defined depending on their bond connectivity, chemical nature and location level (side-chain or backbone). Using this approach it has been possible to obtain average frequencies of pairwise contacts about 15 times higher than the ones obtained using the classic way of one heavy atom definition for each amino acid (i.e. alpha-carbon, beta-carbon, virtual centroid or virtual beta-carbon co-ordinates). In this paper we use this approach to develop a MFP that can be used in fold recognition and we compare it with a classic MFP at the amino acid level compiled from the alpha-carbon distances between the different amino acid pairs. Both potentials involve all the pairwise contacts extracted from a non-redundant folds database of 180 protein chains with a sequence identity threshold of 25%. The pairwise energy functions of the MFP at the atomic level have a deep and very well defined minimum for each pairwise interaction, in contrast to the same curves obtained from the MFP developed at the amino acid level, which generally have multiple minima with similar depth. Our results also show that this MFP is able to produce very similar energy profiles for couples of proteins that share a very low sequence identity but are closely related at the structural level. When these profiles are plotted considering the structure-structure alignment, they are mostly superimposed, showing a correlation with the structure-structure similarity. In the same test, the MFP at the amino acid level fails to produce similar profiles. We suggest that using this MFP at the atomic level in the last stages of fold recognition or threading, when some candidates are available, can improve the sequence-structure alignments and, therefore, the final models. We also discuss the possibility of using this approach in the development of new MFPs to be used in ab initio structure prediction, comparative modelling and molecular recognition procedures.


[Genetic basis of planar polarity].
Several epitheliums exhibit a clear polarity that lies within the plane of the epithelium. This polarity, referred to as planar polarity or tissue polarity, is oriented perpendicular to the apical-basal polarity of the epithelium. Over the last two decades, the genetic and molecular bases of planar polarity have been intensively investigated in Drosophila. Recent studies have shown that establishment of planar polarity relies on the unipolar distribution of a small number of signaling molecules localizing at the apical cortex. Unipolar localization of planar polarity proteins defines two opposite and complementary cortical domains. These domains show a stereotyped orientation at the tissue level. Positioning of these cortical domains is coordinated at the tissue level by a second class of signaling molecules that form an activity gradient across the epithelium. Together these data have led to a general model of planar polarity establishment. Considering that planar polarity genes have been conserved from flies to vertebrates, this model may be useful for our understanding of epithelium biology in mammals.


Prospective analysis of incidence and risk factors of dysphagia in spine surgery patients: comparison of anterior cervical, posterior cervical, and lumbar procedures.
A 3-year prospective, cohort study. To compare the incidence and risk factors of dysphagia after anterior cervical (AC), posterior cervical (PC), and posterior lumbar (PL) spine procedures. Dysphagia is a known risk of AC surgery; however, comprehensive postoperative swallow evaluations have not been performed for a comparative cohort of AC, PC, and PL surgery patients. Eighty-three patients were enrolled in the study, including 38 undergoing AC, 19 PC, and 26 PL procedures. Preoperative and postoperative swallowing evaluations were performed by questioning for subjective swallowing complaints and performing objective radiographic examination. Patients with severe dysphagia leading to an increased risk of aspiration were identified and treated until recovery or for 3 to 9 months. Comparison of preoperative and postoperative swallowing complaints revealed a significant increase for AC patients (P < 0.01) and a trend for PC (P = 0.06) and PL (P = 0.09) patients. Eighteen (47%) AC, 4 (21%) PC, but no PL patients demonstrated dysphagia on postoperative videofluoroscopic swallow evaluation. Age (>60 years, P < 0.01) was associated with increased risk of radiologic evidence of dysphagia. Surgical level, instrumentation, operative time, and presence of myelopathy or other comorbidities were not. Over 70% (12 of 17) of AC patients with dysphagia followed recovered within 2 months, while 23% (4 of 17) required some level of compensatory swallowing behavior up to 10 months following surgery. Dysphagia is a common occurrence after AC procedures but was also found after PC procedures. Intubation alone was not a risk factor for postoperative dysphagia in this cohort.


Contribution of polyamine oxidase to brain injury after trauma.
The possible role of the polyamine interconversion pathway on edema formation, traumatic injury volume, and tissue polyamine levels after traumatic brain injury (TBI) was studied using an inhibitor of the interconversion pathway enzyme, polyamine oxidase. Experimental TBI was induced in Sprague-Dawley rats by using a controlled cortical impact device at a velocity of 3 m/second, resulting in a 2-mm deformation. Immediately after TBI was induced, 100 mg/kg of N1,N4-bis(2,3-butadienyl)-1,4-butanediamine 2HCl (MDL 72527) or saline was injected intraperitoneally. Brain water content and tissue polyamine levels were measured at 24 hours after TBI. Traumatic injury volume was evaluated using 2% cresyl violet solution 7 days after TBI occurred. The MDL 72527 treatment significantly reduced brain edema (80.4+/-0.8% compared with 81.2+/-1.2%, p < 0.05) and injury volume (30.1+/-6.6 mm3 compared with 42.7+/-13.3 mm3, p < 0.05) compared with the saline treatment. The TBI caused a significant increase in tissue putrescine levels at the traumatized site (65.5+/-26.5 nmol/g [corrected] in the cortex and 70.9+/-22.4 nmol/g [corrected] in the hippocampus) compared with the nontraumatized site (7+/-2.4 nmol/g [corrected] in the cortex and 11.4+/-6.4 nmol/g [corrected] in the hippocampus). The increase in putrescine levels in both the traumatized and nontraumatized cortex and hippocampus was reduced by a mean of 60% with MDL 72527 treatment. These results demonstrate, for the first time, that the polyamine interconversion pathway has an important role in the increase of putrescine levels after TBI and that the polyamine oxidase inhibitors, blockers of the interconversion pathway, can be neuroprotective against edema formation and necrotic cavitation after TBI.


Subcellular fractionation studies of human rectal mucosa: localization of the mucosal peptide hormones.
1. Analytical subcellular fractionation techniques have been applied to endoscopic human rectal biopsies to study the localization of enteroglucagon, somatostatin, vasoactive intestinal peptide and the properties of the principal subcellular organelles. 2. The peptide hormones, detected by radioimmunoassay, showed particulate localizations with single peaks in the density gradients for enteroglucagon (modal density 1.25) and somatostatin (modal density 1.23). Vasoactive intestinal peptide showed a less discrete localization but demonstrated a major peak (modal density, 1.17) with a small subsidiary peak (modal density 1.24). 3. The following organelles, characterized by their marker enzymes, were located in the density gradients; plasma membrane (5'-nucleotidase), mitochondria (malate dehydrogenase), peroxisomes (catalase), lysosomes (beta-N-acetyl-D-glucosaminidase), endoplasmic reticulum (neutral alpha-D-glucosidase) and cytosol (lactate dehydrogenase). 4. This technique can be used to investigate disease of the human rectum at a subcellular level.


Heavy metals in water of the San Pedro River in Chihuahua, Mexico and its potential health risk.
The objective of this study was to determine the seasonal and downstream water quality variations of the San Pedro River in Chihuahua, Mexico. Water samples were collected monthly from October 2005 to August 2006 in triplicate, totaling 165 water samples. The five sampling locations were: below the Francisco I. Madero dam (LP); between Rosales and Delicias (RD); Meoqui (M); El Torreon (ET), and Julimes (LJ). The levels of As, Be, Ca, Cd, Co, Cu, Cr, Fe, Li, Mg, Mn, Mo, Ni, Pb, Sb, Se, Sr, Ti, Ta, V and Zn were measured using an Inductively Coupled Plasma- Optical Emission Spectrometry (ICP-OES) Perkin Elmer 2100. In addition, temperature, pH, electrical conductivity and total and fecal coliformes were determined. The statistical analysis considered a factorial treatment design; where factor A was the location point and factor B was sampling date. In addition, a multivariate technique looking for principal components was performed. The results indicated that some samples exceeded Mexican standards for As, Be, Ca, Cd, Co, Cr, Fe, Mn, Ni, Pb, Sb, Se, Sr and Zn. The As level must be considered for a red flag to the communities along the Rio San Pedro because both the monthly average level (0.10 mg L-1) and location (0.10 mg L-1) exceeded the Mexican and International norms. The multivariate analysis showed a predominant aggregation at the LP location, meaning that there was a predominance of As, Sr, Fe and Li. At the rest of the locations the elements did not present a tendency for aggregation. Statistics applied to sampling month showed that December, January, March and April were aggregated in a negative quadrant of component 1 indicating a predominance of V, Ni, Be, Fe and As. Overall, the results confirmed that this stretch of the San Pedro River is contaminated with heavy metals and other contaminants that might affect human health as well as the health of the ecosystem.


Pediatric Lyme Neuroborreliosis: Different clinical presentations of the same agent; Single center experience.
Lyme disease is a vector-associated infectious disease, caused by the agent, spirochete Borrelia burgdorferi. Neurologic findings are observed in approximately 12% of the cases and termed Lyme neuroborreliosis (LNB). Lyme neuroborreliosis may manifest with different clinical neurologic manifestations. The study was conducted at tertiary training and research hospital. From January 2014 to September 2015, a total of 75 patients diagnosed with encephalitis, ataxia, Guillain Barre Syndrome (GBS), facial paralysis, acute disseminated encephalomyelitis (ADEM), pseudotumorcerebri were evaluated for inclusion to the study. Among these patients whom investigations of B. burgdorferi antibody IgM and/or IgG ELISA and Western Blot (WB) were detected to be positive, were assessed. Epidemiologic data, tick bite histories, duration of symptoms, clinical findings, radiologic findings, treatment durations and prognosis were investigated. Totally 7 patients had been treated with the diagnosis of Lyme neuroborreliosis. The mean age was 9.14±4.91 years; duration of symptoms before admission was 8.0±4.50 days; and the duration of antibiotic use was 2.85±0.89 weeks. All patients had received ceftriaxone and intravenous immunoglobulin (IVIG); 3 patients had received plasmapheresis (42.9%) and one patient had received pulse corticosteroid therapy. While the patient with the diagnosis of encephalomyeloneuritis and atypical GBS had partially improved, the other patients were completely cured. In this article, we report pediatric LNB patients, B. burgdorferi should also be considered in patients with atypical or severe neurologic involvement or a history of tick bite; it is known that the prognosis is good with appropriate and early treatment.


Different surface sensing of the cell body and nucleus in healthy primary cells and in a cancerous cell line on nanogrooves.
Cancer cells are known to have alterations compared to healthy cells, but can these differences extend to the way cells interact with their environment? Here, the authors focused on the alignment on an array of grooves of nanometer depth using two cell types: healthy osteoprogenitor primary cells (HOP) and a cancerous osteosarcoma (SaOs-2) cell line. Another concern was how this alignment affects the cell's interior, namely, the nucleus. Based on the results, it is proposed that these two cell types respond to different size regimes: SaOs-2 cells are more sensitive to shallow grooves while HOP cells are strongly aligned with deep grooves. As a measure of the impact of cell alignment on the nucleus the orientation and elongation of the nucleus were determined. Compared to HOP cells, the cell nucleus of SaOs-2 cells is more aligned and elongated in response to grooves, suggesting a softer nucleus and/or increased force transmission. These results support the hypothesis that cancer cells have reduced nucleus rigidity compared to healthy ones and further indicate differences in sensing, which may be important during metastasis.


Selection of lower instrumented vertebra in treating Lenke type 2A adolescent idiopathic scoliosis.
A retrospective, observational, and multicenter study. To identify the ideal lower instrumented vertebra (LIV) to prevent distal adding-on after surgical correction of Lenke type 2A curve. LIV level may affect the risk of postsurgical adding-on. The choice of the last touching vertebra (LTV)-the most caudal vertebra of the main thoracic curve that touches the central sacral vertical line when standing-as an appropriate LIV has been validated for Lenke type 1A but not type 2A curve. Radiographs obtained before, immediately after, and 2 years after surgery were evaluated for 116 consecutive patients who underwent posterior thoracic fusion surgery for Lenke type 2A curve. The LIV was proximal to the LTV in 18 patients (PLTV), distal in 43 (DLTV), and at the LTV in 55 (ALTV). Significant independent factors associated with adding-on were analyzed first by univariate analysis, and then by stepwise logistic regression analysis. Distal adding-on was present in 16 patients (13.8%) at follow-up: 9 PLTV (50.0%), 3 DLTV (7.0%), and 4 ALTV (7.3%). Adding-on was significantly more common in the PLTV group. One PLTV-group patient required revision surgery to treat adding-on. Univariate analysis identified the following significant factors associated with adding-on: the T2-T5 kyphosis angle and shoulder height before, immediately after, and 2 years after surgery; the lumbar Cobb angle at the 2-year follow-up; the 2-year postoperative lumbar curve correction rate; and the difference between the LIV and the end vertebra, neutral vertebra, and LTV levels. Significant independent risk factors identified by stepwise logistic regression analysis included the clavicle angle at follow-up, the correction rate of the lumbar curve immediately after surgery, and the difference between the LIV and LTV levels. A LIV at or distal to the LTV may prevent postoperative adding-on in Lenke type 2A curve. 3.


Incidence of post-abortion intra-uterine adhesions evaluated by hysteroscopy--a prospective study.
A prospective study was conducted on the incidence of intra-uterine pathology diagnosed by hysteroscopy in 147 women who underwent dilatation and sharp curettage due to spontaneous first trimester abortion. The diagnostic hysteroscopies were performed 4-6 weeks after the miscarriage, using CO2 as medium for uterine distention. In 38 patients (25.9%), uterine pathology was found, of whom 28 patients (19%) had intra-uterine adhesions (IUA). The incidence of IUA following only one abortion was 16.3% (16 out of 98 cases), all were of mild extent and filmy consistency, occupying less than one-quarter of the uterine cavity. The incidence of IUA after two abortions was 14% (3/21) but the incidence after three or more spontaneous abortions was significantly elevated (32%, 9/28), (P < 0.05, chi-square test). In addition, 58% of IUA diagnosed in the latter two groups were of a more severe extent. After a first miscarriage, occurrence of post-abortion IUA was not related to the serum oestrogen concentration on the day of curettage, nor was it related to any of the oestrogen treatment modalities used in this study. Although in most of these cases normal recovery of the endometrium was the rule, the high incidence of IUA diagnosed in this prospective study stresses the need for preventive treatment and close follow-up of patients after sharp curettage due to spontaneous abortion. Obviously oestrogen treatment alone did not prove to be effective and other treatment methods should be evaluated. The high incidence and severity of IUA in habitual aborters clearly justifies the performance of a diagnostic hysteroscopy as a standard evaluation.