An outbreak of SHV-5 producing Klebsiella pneumoniae in a neonatal intensive care unit; meropenem failed to avoid fecal colonization.
An outbreak of extended-spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae (ESBL-Kp) in a neonatal intensive care unit prompted a prospective surveillance study between 12th September and 6th October 2003. Surveillance was carried out by obtaining stool samples twice a week. The DNA relatedness of the isolates was shown by random amplified polymorphic DNA comparison (ERIC-PCR). ESBL production was identified by clavulanate synergy, isoelectric focusing, PCR and sequence analysis. During the study period, 49 neonates were hospitalized in the neonatal intensive care unit (NICU). In the first 20-day period, five neonates were infected with ESBL-Kp. The first patient treated with third generation cephalosporin and the second patient treated with meropenem died. While all three infected survivors were clinically improving, the digestive tracts were being colonized by SHV-5 producing Klebsiella. In the next period of the study, five neonates were colonized by ESBL-Kp as well. Univariate comparison of risk factors between colonized and non-colonized neonates was not significant. A total of 24 colonally related ESBL-Kp have been recovered from clinical materials and stool samples. This study demonstrated that parenterally applied meropenem, though successful in treating the systemic illness, might fail to protect the digestive tract from colonization of ESBL-Kp.


Collimator optimization for detection and quantitation tasks: application to gallium-67 imaging.
We describe a new approach to the problem of collimator optimization in nuclear medicine; our methodology is illustrated for the challenging case of gallium-67 imaging. Collimator-design methods based on empirical rules, such as specification of an allowable level of single-septal penetration (SSP) at a fixed energy, are especially inappropriate for radionuclides characterized by an abundance of high-energy contaminant photons that scatter in the patient, collimator, and/or detector before detection within one of a few photopeak energy windows. Lead X-rays produced in the collimator are an additional source of contamination. We designed optimal collimation for 67Ga based on relevant clinical imaging tasks and a realistic simulation of photon transport in a phantom, collimator, and detector. Collimator designs were compared on the basis of performance in lesion detection, as predicted by a three-channel Hotelling observer (CHO), as well as in tumor and background activity estimation (EST), quantified by task-specific signal-to-noise ratios (SNRs). The optimal values of collimator lead content were 22.0 and 23.8 g/cm2, respectively, for CHO and EST, while the optimal geometric resolution values were 1.8 and 1.6 cm full-width at half-maximum (FWHM), respectively, at a distance of 23.5 cm. The resolution of a commercially available medium-energy low-penetration collimator (MELP) is 1.9 cm FWHM at this distance. The optimal values for SSP at 300 keV were 7.3% and 5.8% based on CHO and EST, respectively, compared to 5.2% for the MELP collimator. Compared with the commercial MELP collimator, the 67Ga collimator optimized for tumor detection or activity estimation tasks provided improved geometric spatial resolution with reduced geometric efficiency and, surprisingly, allowed an increased level of single-septal penetration.


Symptoms and impacts of ambulatory nonsense mutation Duchenne muscular dystrophy: a qualitative study and the development of a patient-centred conceptual model.
Duchenne muscular dystrophy is a rare genetic neuromuscular disorder, which can result in early death due to disease progression. Ataluren is indicated for the treatment of nonsense mutation Duchenne muscular dystrophy, in ambulatory individuals aged two years and older. This study explored the symptoms and impacts of nonsense mutation Duchenne muscular dystrophy and experience with ataluren. Qualitative interviews were conducted with caregivers in the UK. Interviews were conducted by telephone, were recorded and transcribed. Data were analysed using thematic analysis and saturation was recorded. Ten interviews were conducted with parents of individuals aged 4-19 years. Key symptoms included muscle weakness and muscle breakdown, which were associated with limitations in physical function and pain. These impacted individuals' daily activities, social activities and emotional wellbeing. These concepts and relationships were illustrated in a conceptual model, along with positive and negative moderating factors. Experience with ataluren and changes since initiation with treatment were discussed. Individuals with nonsense mutation Duchenne muscular dystrophy experience a range of interrelated symptoms and functional issues which impact their broader health-related quality of life. Treatments which address this high unmet need have the potential to improve the health-related quality of life of these individuals.


Multi-array antibody screening in detecting antibodies to mismatched HLA in patients awaiting a second transplant.
Effective identification of HLA specificities to which a prospective transplant recipient has antibodies depends on how effective the most sensitive assay is in detecting these antibodies. To ascertain the assay's efficacy, the results of antibody screening of patients on the waiting list for a second transplant were studied. A commercially available panel of fluoro-coded microbeads coated with multiple and single purified class I or II HLA antigens was used with flow cytometry to detect antibodies in human serum (LABScreen, One Lambda, Canoga Park, Calif, USA). A total of 112 HLA-A, B, and DR mismatches between donors and recipients were present among 34 patients. Antibodies to 56% of the mismatches were detected with 67% of the HLA-A, 38% of the HLA-B, and 63% of the HLA-DR mismatches detected, respectively. Thirty percent of the patients had antibodies to all of the mismatched HLA, 43% had antibodies to some, and 27% did not develop antibodies to any of the mismatched antigens. Among patients who developed antibodies to all of the mismatched HLA, 60% had had a transplant nephrectomy. Only 11% of patients who had no antibodies detected to mismatched HLA had had a transplant nephrectomy and 44% of them were still on immunosuppression. Using the Matchmaker program developed by Duquesnoy, the latter group of patients had a sufficient number of triplet mismatches that could have resulted in an antibody response. All of the undetected antibodies had been identified in other patients in this group. The assay used in this study to detect antibodies is considered the most sensitive one available. Nonetheless, antibodies to slightly less than half of the mismatched HLA antigens were not detected. It appears that the assay system is capable of detecting the antibodies, since in other patients with the same mismatched HLA, antibodies were detected. It is likely that the recipients could develop antibodies since there was a sufficient degree of disparity in the HLA of donors and recipients. Antibodies were more likely to be detected when there had been a transplant nephrectomy and the absence of immunosuppression. There was no way of knowing whether we were missing detecting antibodies or if they were not present. The results of this study have important implications with respect to utilizing "unacceptable antigens" in an allocation system for patients awaiting a second transplant.


Digital spatial profiling of intraductal papillary mucinous neoplasms: Toward a molecular framework for risk stratification.
The histopathologic heterogeneity of intraductal papillary mucinous neoplasms (IPMN) complicates the prediction of pancreatic ductal adenocarcinoma (PDAC) risk. Intratumoral regions of pancreaticobiliary (PB), intestinal (INT), and gastric foveolar (GF) epithelium may occur with either low-grade dysplasia (LGD) or high-grade dysplasia (HGD). We used digital spatial RNA profiling of dysplastic epithelium (83 regions) from surgically resected IPMN tissues (12 patients) to differentiate subtypes and predict genes associated with malignancy. The expression patterns of PB and GF lesions diverged from INT, suggesting that PB and GF arise from a common lineage. Transcriptional dysregulation within PB lesions mirrored that of PDAC, whereas INT and GF foci did not. Tumor necrosis factor/nuclear factor κB (TNF-NFκB) and cell cycle (cycling S and cycling G2-M) programs occurred with relative prominence in PB and INT subtypes, respectively. Together, this study delineates markers of high-risk IPMN and insights into malignant progression.


"I feel like it gives me what I need to know": A qualitative study on adolescent perceptions of two contraceptive decision aids.
We sought to understand how adolescents perceive two commonly used contraceptive decision aids and which elements adolescents identified as most important to them. We conducted a cross-sectional qualitative study of adolescents' perceptions of two decision aids, Your Birth Control Choices designed by the Reproductive Health Access Project and Birth Control: What's Important to You? designed by Power to Decide for Bedsider.org. We conducted semistructured interviews with 20 adolescents (aged 15-19 years) who were assigned female sex at birth and attended a single clinic in North Carolina. Interview questions addressed the decision aids' aesthetic design, informational content, inclusivity, and comprehensibility. We transcribed and analyzed interviews using Dedoose software. We developed a codebook using a combination of a priori and inductive codes followed by content analysis to identify themes. All participants agreed that both decision aids could be helpful with contraceptive decision-making and with patient-provider discussions. However, some phrasing and descriptions of contraceptive methods were confusing. Participants preferred realistic imagery, clear explanations of side effects, and details on method use. Participants expressed a preference for the information contained in the detailed Reproductive Health Access Project decision aid, while most favored the aesthetic design and layout of the Bedsider decision aid. Although adolescents expressed sentiments of increased knowledge and empowerment after reviewing the decision aids, this study suggests neither decision aid completely meets adolescent needs and preferences. Additional adaptations are necessary to create adolescent-centered contraceptive decision aids. Adolescents in this study found two contraceptive decision aids as useful adjuncts to conversations with providers. The decision aids improved contraceptive knowledge and may facilitate decision-making. However, neither of the studied decision aids fully met the perceived needs of adolescents. Future adaptations or designs should include additional adolescent-centered content.


Study of montelukast for the treatment of respiratory symptoms of post-respiratory syncytial virus bronchiolitis in children.
A pilot study (Bisgaard H; Study Group on Montelukast and Respiratory Syncytial Virus. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir Crit Care Med 2003;167:379-383) reported the efficacy of montelukast in post-respiratory syncytial virus (RSV) bronchiolitic respiratory symptoms. To evaluate the efficacy and safety of montelukast, 4 and 8 mg, in treating recurrent respiratory symptoms of post-RSV bronchiolitis in children in a large, multicenter study. This was a double-blind study of 3- to 24-month-old children who had been hospitalized for a first or second episode of physician-diagnosed RSV bronchiolitis and who tested positive for RSV. Patients (n = 979) were randomized to placebo or to montelukast at 4 or 8 mg/day for 4 weeks (period I) and 20 weeks (period II). The primary end point was percentage symptom-free days (%SFD; day with no daytime cough, wheeze, and shortness of breath, and no nighttime cough). No significant differences were seen between montelukast and placebo in %SFD over period I: mean +/- SD for placebo and for montelukast at 4 and 8 mg were 37.0 +/- 30.7, 38.6 +/- 30.4, and 38.5 +/- 29.9, respectively. Least-squares mean differences (95% confidence interval) between montelukast (4 mg) and placebo and between montelukast (8 mg) and placebo were 1.9% (-2.9, 6.7) and 1.6% (-3.2, 6.5), respectively. Secondary end points were similar across treatments. Both doses were generally well tolerated. During the first two treatment weeks, average %SFD was approximately 29%. In post hoc analyses of patients (n = 523) with persistent symptoms (%SFD < or = 30% over Weeks 1-2), differences in %SFD were seen between montelukast and placebo over Weeks 3-24: difference were 5.7 (0.0, 11.3) for montelukast (4 mg) minus placebo and 5.9 (0.1, 11.7) for montelukast (8 mg) minus placebo. In this study, montelukast did not improve respiratory symptoms of post-RSV bronchiolitis in children.


Isolation of genomic DNA fragments corresponding to genes modulated in vivo by a transcription factor.
A new methodology for the identification of genes modulated by transcription factors in vivo is described. Mouse genomic DNA fragments bound by the thyroid hormone receptor (T3R) were selected and amplified in vitro. Subsequent hybridisation with biotinylated cDNA allowed the selection of those DNA fragments containing binding sites for T3R that corresponded to transcribed DNA. Expression analysis of the corresponding genes showed that more than 80% are indeed modulated by thyroid hormones in vivo in the liver. Together with the presence of consensus binding sites for T3R this result suggests that the selected DNA fragments may contain T3R transcriptional regulatory elements. This method, extensive to other ligand-modulated transcription factors, might be useful to all transcription factors with slight modifications.


[Venous wall graft in Peyronie's disease (author's transl)].
One patient with Peyronie's disease (induratio penis plastica) was treated utilizing plastic surgery to correct the penile curvature. The plaques which invaded the corpora were transversely incised and a section of the greater saphenous vein was sewn into the gap. Postoperatively, the penis is quite straight and the patient has resumed normal sexual intercourse.


Possible role of glutamine synthetase of the prokaryotic type (GSI-like) in nitrogen signaling in Medicago truncatula.
Genes containing domains related to glutamine synthetase of the prokaryotic type (GSI-like) are widespread in higher plants, but their function is currently unknown. To gain insights into the possible role of GSI-like proteins, we characterized the GSI-like gene family of Medicago truncatula and investigated the functionality of the encoded proteins. M. truncatula contains two-expressed GSI-like genes, MtGSIa and MtGSIb, encoding polypeptides of 454 and 453 amino acids, respectively. Heterologous complementation assays of a bacterial glnA mutant indicate that the proteins are not catalytically functional for glutamine synthesis. Gene expression was investigated by qRT-PCR and western blot analysis in different organs of the plant and under different nitrogen (N) regimes, revealing that both genes are preferentially expressed in roots and root nodules, and that their expression is influenced by the N-status of the plant. Analysis of transgenic plants expressing MtGSI-like-promoter-gusA fusion, indicate that the two genes are strongly expressed in the root pericycle, and interestingly, the expression is enhanced at the sites of nodule emergence being particularly strong in specific cells located in front of the protoxylem poles. Taken together, the results presented here support a role of GSI-like proteins in N sensing and/or signaling, probably operating at the interface between perception of the N-status and the developmental processes underlying both root nodule and lateral root formation. This study indicates that GSI-like genes may represent a novel class of molecular players of the N-mediated signaling events.


On the impact of attention and motor planning on the lateral geniculate nucleus.
Although the lateral geniculate nucleus (LGN) is one of the most thoroughly characterized thalamic nuclei, its functional role remains controversial. Traditionally, the LGN in primates has been viewed as the lowest level of a set of feedforward parallel visual pathways to cortex. These feedforward pathways are pictured as connected hierarchies of areas designed to construct the visual image gradually - adding more complex features as one marches through successive levels of the hierarchy. In terms of synapse number and circuitry, the anatomy suggests that the LGN can be viewed also as the ultimate terminus in a series of feedback pathways that originate at the highest cortical levels. Since the visual system is dynamic, a more accurate picture of image construction might be one in which information flows bidirectionally, through both the feedforward and feedback pathways constantly and simultaneously. Based upon evidence from anatomy, physiology, and imaging, we argue that the LGN is more than a simple gate for retinal information. Here, we review evidence that suggests that one function of the LGN is to enhance relevant visual signals through circuits related to both motor planning and attention. Specifically, we argue that major extraretinal inputs to the LGN may provide: (1) eye movement information to enhance and bind visual signals related to new saccade targets and (2) top-down and bottom-up information about target relevance to selectively enhance visual signals through spatial attention.


Protein translocation: what's the problem?
We came together in Leeds to commemorate and celebrate the life and achievements of Prof. Stephen Baldwin. For many years we, together with Sheena Radford and Roman Tuma (colleagues also of the University of Leeds), have worked together on the problem of protein translocation through the essential and ubiquitous Sec system. Inspired and helped by Steve we may finally be making progress. My seminar described our latest hypothesis for the molecular mechanism of protein translocation, supported by results collected in Bristol and Leeds on the tractable bacterial secretion process-commonly known as the Sec system; work that will be published elsewhere. Below is a description of the alternative and contested models for protein translocation that we all have been contemplating for many years. This review will consider their pros and cons.


Race, socioeconomic status, and domestic homicide, Atlanta, 1971-72.
It has been assumed that, under comparable socioeconomic conditions, Blacks are more likely than Whites to commit violent acts. To test this assumption, 222 intra-racial domestic homicides (186 Black and 36 White victims) committed in Atlanta, 1971-1972, were subjected to analysis. A domestic homicide was defined as a criminal homicide committed in a residence by a relative or acquaintance of the victim. When Black and White populations were unmatched, the relative risk of intra-racial domestic homicide in Black populations was 5.8 (95 per cent C.I.: 4.3-8.0). When Black and White populations were matched for rates of household crowding, the relative risk of intra-racial domestic homicide in Black populations was no longer significantly elevated (relative risk = 1.2; 95 per cent C.I.: 0.7-2.0). Using rates of household crowding as an index of socioeconomic status, Atlanta Blacks were no more likely to commit domestic homicide than were Whites in comparable socioeconomic circumstances. Further research is needed to determine whether household crowding per se is a risk factor for domestic homicide, independent of socioeconomic status.


Transrectal three-dimensional fetal volumetry in early pregnant mares: Relationships between maternal factors and equine fetal volume measurements.
The aim of this study was to investigate the effects of maternal, hormonal, and fetal factors on early fetal volume (FV) measurements in mares obtained by three-dimensional (3D) ultrasound. Furthermore, postpartum parameters were explored in regard to their association with early FV. For this purpose, 149 German warmblood mares that were artificially inseminated and confirmed to be pregnant between days 14-16 of gestation, were examined transrectally at day 45 ± 1 of gestation with the portable 3D ultrasound device Voluson® i (GE, Zipf, Austria). FV was calculated by using the extension software Virtual Organ Computer-aided AnaLysis (VOCAL™). Two different mixed linear models were used to analyze associations between the investigated maternal and fetal factors and the FV. Explanatory variables investigated in the first model were: maternal age, parity, maternal weight, and body condition score, type of pregnancy (recipient or biological mother), barren status (lactating or non-lactating), fetal sex, progesterone (P4) and equine chorionic gonadotropin (eCG) concentrations; and in the second model outcome variables such as gestational length, birth weight, placental weight, fetal sex, and abortion were included in the analysis. The final models revealed a significant relation between FV and eCG (b = 0.011, P = 0.030), as well as with P4 (b = -0.053, P = 0.016), but interestingly P4 was negatively related to FV. Fetal sex showed the most prominent effect on FV (b = -0.256, P = 0.039), with female fetuses being smaller than male fetuses. In the second model none of the investigated parameters were related to early FV except for fetal sex (b = -0.328, P = 0.047), again with female fetuses being smaller. In summary, it was found that FV is related with eCG, P4 and fetal sex, but was no suitable predicting factor for the investigated outcome parameters. Furthermore, the findings suggest that sex specific growth differences exist already in early gestation. The detailed biological mechanism by which P4 and eCG affect fetal size has to be investigated in prospective studies.


Collagen matrix scaffolds: Future perspectives for the management of chronic liver diseases.
Approximately 1.5 billion chronic liver disease (CLD) cases have been estimated worldwide, encompassing a wide range of liver damage severities. Moreover, liver disease causes approximately 1.75 million deaths per year. CLD is typically characterized by the silent and progressive deterioration of liver parenchyma due to an incessant inflammatory process, cell death, over deposition of extracellular matrix proteins, and dysregulated regeneration. Overall, these processes impair the correct function of this vital organ. Cirrhosis and liver cancer are the main complications of CLD, which accounts for 3.5% of all deaths worldwide. Liver transplantation is the optimal therapeutic option for advanced liver damage. The liver is one of the most common organs transplanted; however, only 10% of liver transplants are successful. In this context, regenerative medicine has made significant progress in the design of biomaterials, such as collagen matrix scaffolds, to address the limitations of organ transplantation (e.g., low donation rates and biocompatibility). Thus, it remains crucial to continue with experimental and clinical studies to validate the use of collagen matrix scaffolds in liver disease.


Effects of Low-Intensity Exercise in Older Adults With Chronic Heart Failure During the Transitional Period From Hospital to Home in China: A Randomized Controlled Trial.
The transitional period from hospital to home is critical to decreasing rates of preventable, poor post-discharge outcomes. Older adults with chronic heart failure (CHF) may be challenged to exercise during the transitional period. The purpose of the current study was to test the effects of low-intensity exercise on health-related quality of life (HRQoL), physical function, and heart function in Chinese older adults with CHF during the transitional period. The study was randomized, single-blinded, and controlled. Seventy-eight older adults with stable CHF were evaluated. The intervention group (n = 41) participated in a regular low-intensity walking protocol and the control group (n = 38) did not. Measures included the Minnesota Living with Heart Failure Questionnaire (MLHFQ), 6-minute walk distance (6MWD), Timed Up and Go (TUG) test, resting heart rate (RHR), and left ventricular ejection fraction (LVEF). After 12 weeks, the intervention group showed significant improvements in MLHFQ, 6MWD, and TUG scores compared to the control group (p < 0.05), and no significant improvements in RHR and LVEF (p > 0.05). Low-intensity exercise during the transitional period is an effective way to improve HRQoL and physical function in older adults. [Res Gerontol Nurs. 2017; 10(3):121-128.].


High-Quality Genome Assembly of Chrysaora quinquecirrha Provides Insights Into the Adaptive Evolution of Jellyfish.
Jellyfish, such as Chrysaora quinquecirrha, hold an important evolutionary position and have great ecological value. However, limited genomic resources are currently available for studying their basic genetic and development processes. Here, we de novo assembled the first high-quality reference genome of C. quinquecirrha, and successfully annotated 21,606 protein-coding genes. Codon usage analysis identified the frequent use of low-GC-content codons during protein-coding gene translation. Analysis of the relative evolution rate indicated that jellyfish had a faster evolution rate than sea anemones but slower rate than the species in Hydra. Phylogenetic analysis with two other species of jellyfish indicated that Aurelia aurita and Nemopilema nomurai have a closer relationship with each other than with C. quinquecirrha, with divergence from their common ancestor occurring ≈475.7 million years ago. Our study not only showed the genomic characteristics and molecular adaptive evolution of C. quinquecirrha, but also provides valuable genomic resources for further study on complex developmental processes and environmental adaptations.


Dietary constraints can preclude the expression of an honest chemical sexual signal.
Identifying the factors that underlie signal divergences remains challenging in studies of animal communication. Regarding the chemical signalling, different compounds can be found in some species but be absent in others. We hypothesized that if the costs that are associated with the expression of some compounds are too high, their presence in the signal may be restricted. However, these compounds may be expressed and be functional when those costs are relaxed. Vitamin E (α-tocopherol), a dietary compound with metabolic relevancy, acts as an honest chemical sexual signal in many lizards but no in others such as the Carpetan Rock lizard (Iberolacerta cyreni). We investigated whether dietary supplementation favours the expression of this vitamin in scents of I. cyreni. We show that dietary constraints can preclude the expression of vitamin E in chemical secretions of wild males because was expressed when it was experimentally provided in the diet. Vitamin E supplementation also heightened the immune response of males and increased the interest of their scent for females, highlighting the vitamin E as a chemical sexual signal in this species. We suggest that diet could decisively act as a driver of intra- and interspecific divergences in the chemical signalling of lizards.


Multi-focus composite spiral zone plate to generate focused vortices with the comparable intensity based on genetic algorithm.
In this study, we introduce an optical element, named Multi-focus Composite Spiral Zone Plate (MFCSZP), to generate multi focused vortices with approximately equal intensity along the optical axis. The genetic algorithm (GA) is used to optimize the parameters of the MFCSZP, which avoids manual parameter adjustment and improves computational efficiency. We analyze the focusing properties of the constructed MFCSZP theoretically and experimentally. The results provide evidence for its capability to generate multiple focused vortices with comparable peak intensities verified through experiment. This work shows the powerful ability of intelligent algorithms in the optimization of complex optical elements. The proposed optical element showcases potential applications within research areas of optical trapping and laser machining.


[Role of PI3K/Akt signaling pathway in ischemic rats underwent cardiac shock waves therapy].
Objective: To investigate the role of PI3K/Akt signaling pathway in ischemic rats underwent cardiac shock therapy. Methods: Adult male Sprague Dawley (SD) rats weighing 220-250 g were used to establish a heart failure model by ligation of the left anterior descending coronary artery. Rat models were defined by echocardiographic assessment at 4 weeks post operation and heart failure rats were randomly divided into 4 groups,namely heart failure group (HF group, 9 cases),heart failure+cardiac shock waves therapy group (HF+CSWT group, 9 cases),heart failure+inhibitor(HF+LY294002 group, 9 cases),heart failure+cardiac shock waves therapy group+inhibitor (HF+CSWT+LY294002 group, 9 cases),and another 9 sham-operated SD rats served as control group (sham group, 9 cases). At 8 weeks postoperation, echocardiography was used to evaluate cardiac function in each group,myocardial infarct size was measured by TTC staining,the apoptotic index of rats cardiomyocytes were detected by TUNEL method,the myocardial mRNA expression of apoptosis-related factor was detected by real-time quantitative PCR, the protein expression levels of PI3K/Akt signaling pathway and apoptosis-related pathways were detected by Western blot. Results: (1) Eight weeks after operation, left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) were significantly lower in HF+CSWT group than in HF group (all P<0.05), left ventricular ejection fraction (LVEF) and left ventricular shortening rate (LVFS) were significantly higher in HF+CSWT group than in HF group (all P<0.05),LVEF was significantly lower in the HF+ CSWT+ LY294002 group than in HF+ CSWT group (P<0.05). (2) Myocardial infarct size was significantly lower in the HF+ CSWT group than in HF group ((5.57 ± 0.51)% vs. (25.56 ± 0.56)%, P<0.05), which was significantly higher in the HF+CSWT+LY294002 group than in HF+CSWT group ((12.90±2.34)% vs. (5.57±0.51)%,P<0.05). (3) The cardiomyocyte apoptotic index was significantly lower in the HF+CSWT group than in the HF group ((30.25±6.12)% vs. (53.85±9.89)%,P<0.05), which was significantly higher in the HF+CSWT+LY294002 group than in the HF+CSWT group ((46.12±3.42)% vs.(30.25±6.12)%,P<0.05). (4) The myocardial mRNA expression of Bcl-2 was significantly higher, while myocardial mRNA Bax and Caspase-3 expression were significantly lower in HF+CSWT group than in HF group and HF+CSWT+LY294002 group (all P<0.05). (5) The expression levels of p-Akt, Bcl-2 and pro-Caspase-3 in myocardial tissue were significantly higher in the HF+CSWT group than in the HF group and HF+CSWT+LY294002 group (all P<0.05), which were significantly lower in the HF+LY294002 group than in the HF and HF+CSWT+LY294002 groups (all P<0.05). Myocardial Bax protein expression was significantly lower in the HF+CSWT group than in the HF group and the HF+CSWT+LY294002 group (all P<0.05), which was significantly higher in the HF+LY294002 group than in the HF group (P<0.05). Conclusion: CSWT improves cardiac function and inhibits cardiomyocyte apoptosis through PI3K/Akt signaling pathways in this rat HF model.


Modulation of inflammation by toll-like receptor 4/nuclear factor-kappa B in diarrhea-predominant irritable bowel syndrome.
In order to investigate the function of toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signal pathways in the pathogenesis of diarrhea-predominant irritable bowel syndrome (IBS-D), IBS-D animal models were established in wistar rats challenged with acute and chronic stresses (29 days). Wistar rats without stress-challenged were used as controls. IBS-D models were randomly divided into two groups: one was treated with normal saline, another group was treated with TLR4/NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC) (50mg/kg/week) for continuous four times. Our results demonstrate that continuous stresses can induce the characteristic symptoms of IBS-D, including high wet stool rate and intestinal flora imbalance. Further examinations of colon tissues show that the protein expression levels of TLR4 and NF-κB in IBS-D groups are higher than that in control group. The secretory levels of interleukin (IL-8), tumor necrosis factor α (TNFα), and myeloid differentiation factor 88 (MyD88) are significantly increased in IBS-D group. Administration with PDTC effectively downregulates levels of these inflammatory factors. In contrast, interleukin-10 (IL-10) is in an opposite alteration with lower levels in IBS-D groups and the PDTC treatment increases it to the levels as in control group. Moreover, inhibition of the TLR4/NF-κB by PDTC improves the microstructure of intestinal mucosa mainly by increasing the height of villi. Our results suggest that TLR4/NF-κB signal pathway plays an important role in the modulation of inflammatory responses in IBS-D, which might be a therapeutic target for the IBS-D. All of these findings also provide the evidence concerning an inherent linkage between the axis of stress/NF-κB/inflammation and IBS-D.


Thoracic stent grafts with a distal fenestration for the celiac axis.
Descending thoracic aneurysms can be treated with a stent graft provided that there is sufficient proximal and distal aortic neck length above the celiac axis. One of the options for the treatment of thoracic aneurysms with a too short distal neck is described in this report. For this purpose, a stent graft was constructed with a scallop for the celiac axis. Three cases are presented, and the technical details are described.


Allergic conjunctivitis.
The purpose of this research is to study the clinical features and risk factors of various types of allergic conjunctivitis. Four hundred and forty-five patients with a history of itching, foreign body sensation, lacrimation and red eyes were examined, and a skin test was performed and assessed to grade the severity. The mean age of the subjects was 24.5 +/- 16.3 years with female preponderance, except for vernal keratoconjunctivitis. The majority of the patients had perennial allergic conjunctivitis. Ninety-five percent of the patients had associated allergic diseases, especially allergic rhinitis. Sixty-six percent of the patients had a family history of atopy. Most patients had symptoms at night. Symptoms persisted throughout the year and were generally triggered by exposure to house dust. The allergy skin tests to common aero-allergens were positive in 95% of patients tested. Common allergens causing sensitization were house-dust mites, house dust, cockroaches, and grass pollen. Environmental control and avoidance of these allergens should be stressed in the management of these conditions.


Identification of ciliary and ciliopathy genes in Caenorhabditis elegans through comparative genomics.
The recent availability of genome sequences of multiple related Caenorhabditis species has made it possible to identify, using comparative genomics, similarly transcribed genes in Caenorhabditis elegans and its sister species. Taking this approach, we have identified numerous novel ciliary genes in C. elegans, some of which may be orthologs of unidentified human ciliopathy genes. By screening for genes possessing canonical X-box sequences in promoters of three Caenorhabditis species, namely C. elegans, C. briggsae and C. remanei, we identified 93 genes (including known X-box regulated genes) that encode putative components of ciliated neurons in C. elegans and are subject to the same regulatory control. For many of these genes, restricted anatomical expression in ciliated cells was confirmed, and control of transcription by the ciliogenic DAF-19 RFX transcription factor was demonstrated by comparative transcriptional profiling of different tissue types and of daf-19(+) and daf-19(-) animals. Finally, we demonstrate that the dye-filling defect of dyf-5(mn400) animals, which is indicative of compromised exposure of cilia to the environment, is caused by a nonsense mutation in the serine/threonine protein kinase gene M04C9.5. Our comparative genomics-based predictions may be useful for identifying genes involved in human ciliopathies, including Bardet-Biedl Syndrome (BBS), since the C. elegans orthologs of known human BBS genes contain X-box motifs and are required for normal dye filling in C. elegans ciliated neurons.


Neuropathologic features, including pontine schwannosis, in a four-year survivor of probable Reye's syndrome with secondary Möbius syndrome.
Frequent seizures and loss of motor, language, and intellectual skills necessitated care in an institution for the physically and mentally handicapped for 4 years after diagnosis of presumed Reye's syndrome in a 10-month-old boy. M obius syndrome was diagnosed and bilateral tarsorrhaphy performed for exposure keratitis. Postmortem examination revealed multiple old boundary zone infarcts in the cerebral cortex, small cavitated infarcts in basal ganglia and thalami, diffuse neuronal loss and gliosis, and a focus of old necrosis in the pons; brain stem herniation during the acute phase of Reye's syndrome was responsible for the latter lesion. Irregular congeries of proliferated peripheral nerves, confirmed by ultrastructural study, were ramifying in the gliotic pontine tegmentum. The pathologic substrate for the neurovegetative state in a long-term survivor of probable Reye's syndrome appears to be multifocal cerebral infarction.


A first-principles polarized Raman method for determining whether a uniform region of a sample is crystalline or isotropic.
Previous methods for determining whether a uniform region of a sample is crystalline or isotropic-what we call the "state of internal orientation" S-require a priori knowledge of properties of the purely crystalline and purely isotropic states. In addition, these methods can be ambiguous in their determination of state S for particular materials and, for a given material, the spectral methods can be ambiguous when using particular peaks. Using first-principles Raman theory, we have discovered a simple, non-resonance, polarized Raman method for determining the state S that requires no information a priori and will work unambiguously for any material using any vibrational mode. Similar to the concept behind "magic angle spinning" in NMR, we have found that for a special set of incident/analyzed polarizations and scattering angle, the dependence of the Raman modulation depth M on the sample composition-and, for crystalline regions, the unit cell orientation-falls out completely, leaving dependence on only whether the region is crystalline (M = 1) or isotropic (M = 0). Further, upon scanning between homogeneous regions or domains within a heterogeneous sample, our signal M is a clear detector of the region boundaries, so that when combined with methods for determining the orientations of the crystalline domains, our method can be used to completely characterize the molecular structure of an entire heterogeneous sample to a very high certainty. Interestingly, our method can also be used to determine when a given mode is vibrationally degenerate. While simulations on realistic terthiophene systems are included to illustrate our findings, our method should apply to any type of material, including thin films, molecular crystals, and semiconductors. Finally, our discovery of these relationships required derivations of Raman intensity formulas that are at least as general as any we have found, and herein we present our comprehensive formulas for both the crystalline and isotropic states.


[Chapter 3. How to improve the sharing of data collected during research conducted in countries with limited resources].
On the 5th of November 2015, the Inserm Ethics Committee, Fondation Mérieux and the Global Forum on Bioethics in Research (GFBR), organized a workshop at Les Pensières, Annecy, France, bringing together more than thirty scientists and ethicists, from twenty countries around the world, to debate the way to ensure better sharing of data and biological samples collected during trials in countries with limited resources.Propositions were made to improve the practices of different stakeholders of scientific research (researchers, members of ethics committees, key community representatives) and policy makers (ministers, funding agencies), on the following issues :How to foster equitable scientific collaborations in international research projects ?How to protect the interests of the study participants when sharing data and biological samples ?How to ensure appropriate information and obtain informed consent from individuals with different cultures and levels of education ?In this publication on the use of ?big data? in health, this report from the workshop of November 5, focuses on the aspects related to the sharing of research data.


Infrapatellar hypertrichosis: an unusual cutaneous manifestation of juvenile dermatomyositis.
Juvenile dermatomyositis (JDM) is an uncommon inflammatory myopathy with characteristic cutaneous manifestations. Certain clinical features such as cutaneous calcification, lipoatrophy, and generalized hypertrichosis can occur in JDM but are uncommon in the adult form of the disease. We report a young girl who presented with dramatic infrapatellar hypertrichosis along with more classic clinical signs of JDM, including heliotrope periorbital eruption, photosensitivity, and profound proximal muscle weakness. The clinical course was favorable, with improvement of cutaneous and muscular abnormalities after corticosteroid treatment.


Involvement of the Rostromedial Prefrontal Cortex in Human-Robot Interaction: fNIRS Evidence From a Robot-Assisted Motor Task.
Assistive exoskeleton robots are being widely applied in neurorehabilitation to improve upper-limb motor and somatosensory functions. During robot-assisted exercises, the central nervous system appears to highly attend to external information-processing (IP) to efficiently interact with robotic assistance. However, the neural mechanisms underlying this process remain unclear. The rostromedial prefrontal cortex (rmPFC) may be the core of the executive resource allocation that generates biases in the allocation of processing resources toward an external IP according to current behavioral demands. Here, we used functional near-infrared spectroscopy to investigate the cortical activation associated with executive resource allocation during a robot-assisted motor task. During data acquisition, participants performed a right-arm motor task using elbow flexion-extension movements in three different loading conditions: robotic assistive loading (ROB), resistive loading (RES), and non-loading (NON). Participants were asked to strive for kinematic consistency in their movements. A one-way repeated measures analysis of variance and general linear model-based methods were employed to examine task-related activity. We demonstrated that hemodynamic responses in the ventral and dorsal rmPFC were higher during ROB than during NON. Moreover, greater hemodynamic responses in the ventral rmPFC were observed during ROB than during RES. Increased activation in ventral and dorsal rmPFC subregions may be involved in the executive resource allocation that prioritizes external IP during human-robot interactions. In conclusion, these findings provide novel insights regarding the involvement of executive control during a robot-assisted motor task.


A calcite permeable reactive barrier for the remediation of Fluoride from spent potliner (SPL) contaminated groundwater.
The use of calcite (CaCO3) as a substrate for a permeable reactive barrier (PRB) for removing fluoride from contaminated groundwater is proposed and is illustrated by application to groundwater contaminated by spent potliner leachate (SPL), a waste derived from the aluminium smelting process. The paper focuses on two issues in the implementation of calcite permeable reactive barriers for remediating fluoride contaminated water: the impact of the groundwater chemical matrix and CO2 addition on fluoride removal. Column tests comparing pure NaF solutions, synthetic SPL solutions, and actual SPL leachate indicate that the complex chemical matrix of the SPL leachate can impact fluoride removal significantly. For SPL contaminant mixtures, fluoride removal is initially less than expected from idealized, pure, solutions. However, with time, the effect of other contaminants on fluoride removal diminishes. Column tests also show that pH control is important for optimizing fluoride removal with the mass removed increasing with decreasing pH. Barrier pH can be regulated by CO2 addition with the point of injection being critical for optimising the remediation performance. Experimental and model results show that approximately 99% of 2300 mg/L fluoride can be removed when CO2 is injected directly into the barrier. This can be compared to approximately 30-50% removal when the influent solution is equilibrated with atmospheric CO2 before contact with calcite.


Health-related quality of life of patients with cystic fibrosis assessed by the SF-36 questionnaire.
Cystic fibrosis (CF) is a genetic disorder, which is most common among Caucasians. There are about 100,000 people suffering from this disorder in the world, including 25 000 in Europe. Although the first mention of cystic fibrosis is thought to have occurred in 1595, recognition of the entire clinical spectrum of CF and the resultant development of contemporary knowledge occurred in the 20th century. In the past, CF was considered a fatal childhood disorder; however, contemporary statistical data shows that 50% of people with cystic fibrosis have a chance to live up to 30 years of age, and the lifespan of children born in the 1990s is projected to be at least 40 years. Consequently, the number of adults with cystic fibrosis is increasing, making it necessary for multidisciplinary actions aimed at the improvement of clinical management of the condition as well as minimizing the influence of CF and its treatment on the quality of continually extending life of patients. Since cystic fibrosis interferes with almost all important aspects of human functioning, quality of life (QoL) of individuals with CF should be constantly and closely monitored, thus allowing for consideration of their needs and providing an opportunity to modify the therapeutic approach if necessary. The aim of this study was to visualize the QoL of people with cystic fibrosis, to identify differences in their assessment of QoL depending on sex and age, as well as to compare the QoL of patients with CF with a control group of people without CF. The study was conducted among patients hospitalized at the Clinic of Pulmonology and Cystic Fibrosis at the Institute of Tuberculosis and Lung Diseases in Rabka-Zdrój from February to April 2012. The study encompassed 30 patients (19 women and 11 men), aged between 16 and 42 years, with acute episodes of bronchopulmonary disease. A Short Form-36 (SF-36) questionnaire was used to evaluate the health-related quality of life. The control group encompassed 30 healthy individuals with the same sex ratio and similar age ratio as in the group of patients. The analysis of quality of life with the use of the SF-36 questionnaire showed that in general the quality of life of the assessed patients was low. The patients scored on average below 50 in the following subscales: Role Physical (RP), General Health (GP), Vitality (VT), Social Functioning (SF), Physical Component Summary (PCS) and Mental Component Summary (MCS). In other subscales the results slightly exceeded 50. In women, low quality of life was found in the following subscales: Role Physical, Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Physical Component Summary (PCS) and Mental Component Summary (MCS). In men, average results below 50 were found in the following subscales: General Health (GH) and Vitality (VT). Moreover, in all subscales, the quality of life assessed by women was lower than that reported by men.Patients > 25 years assessed their quality of life as lower in all subscales except for the Role Emotional (RE) subscale. Statistically significant differences were identified with regards to Vitality (VT) and Mental Health (MH). The analysis of the influence of CF patients' age on their quality of life, conducted with the use of the SF-36 questionnaire, showed that there were statistically significant correlations (p < 0.05) between age and the following domains: Physical Functioning (PF), Role Physical (RP), Bodily Pain (BP), Vitality (VT), Social Functioning (SF), Mental Health (MH) and Physical Component Summary (PCS). The comparison between the QoL of patients with CF and those of a control group of individuals not suffering from CF demonstrated that there were statistically significant differences in all subscales. Patients' quality of life was significantly poorer than quality of life of individuals without CF. 1. Patients with CF generally perceive their quality of life as low.2. There are differences in the assessment of quality of life between women and men.3. The older the patients, the worse their quality of life assessment in most subscales.4. There are critical differences in the quality of life assessment between patients with CF and a control group encompassing individuals without CF. Patients with CF find their quality of life poorer.


Neurotransmitter-mediated signaling between axons and glial cells.
Neurotransmitter-mediated signaling is not restricted to the synaptic regions of the nervous system but also takes places along fiber tracts lacking vesicular means of releasing neuroactive substances. The first demonstration for dynamic signaling of this type came in the early 1970s from studies by Villegas and co-workers in squid axons and their satellite Schwann cells. In this invertebrate system, glutamate has been identified as the mediator of this signaling in being first released from the active axons thus setting off a series of cascades, leading to a cholinergic activation of the Schwann cell membrane. Recent evidence suggests that receptor-mediated signaling also exists between glial cells and axons in vertebrates. In the frog optic nerve, axonal activity facilitated the activity of glial ion channels. In the neonatal rat optic nerve, electrical activity of axons triggered oscillations in intracellular calcium in a subset of glial cells. These observations have been postulated to reflect receptor-mediated signaling, including a mechanism in which glutamate is released from axons via the reversal of a transporter and induces intracellular calcium spiking in glial cells via metabotropic glutamate receptors. The efficacy of "axon-to-glia" transmission may, like that in "neuron-to-neuron" transmission, be modulated by co-release of multiple neuroactive substances. One possibility is that adenosine, which is known to be released from fiber tracts, can modulate glutamate signaling in white matter by modulating the periaxonal glutamate concentration through an effect on the glial glutamate uptake system.


Distinguishing conversion disorder from neurologic impairment.
Hysteria/conversion disorder has been described since antiquity. One French neurologist dubbed it "neurological nonsense" because its presentation was so complex and confusing. For nosological purposes for inclusion into the Diagnostic Statistical Manual, multiple revisions of conversion disorder terminology were made for each edition published from 1952-1994. Until recently, conversion disorder was thought to be solely psychological in origin: new studies raise the possibility that what is called conversion disorder is actually early disruption in the functioning of the nervous system in predisposed individuals. Because of its uncanny resemblance to neurological disease, the differential diagnosis is critical and should be exhaustive in its efforts to rule out neurological disease. The neuroscience nurse needs to be aware of this perplexing syndrome called conversion disorder and the never theories that suggest organic causation and interventions to enhance recovery.


Animal models of Huntington's disease: implications in uncovering pathogenic mechanisms and developing therapies.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, which is caused by an abnormal expansion of Cytosine Adenine Guanine (CAG) trinucleotide repeat in the gene making huntingtin (Htt). Despite intensive research efforts devoted to investigate molecular mechanisms of pathogenesis, effective therapy for this devastating disease is still not available at present. The development of various animal models of HD has offered alternative approaches in the study of HD molecular pathology. Many HD models, including chemical-induced models and genetic models, mimic some aspects of HD symptoms and pathology. To date, however, there is no ideal model which replicates all of the essential features of neuropathology and progressive motor and cognitive impairments of human HD. As a result, our understanding of molecular mechanisms of pathogenesis in HD is still limited. A new model is needed in order to uncover the pathogenesis and to develop novel therapies for HD. In this review we discussed usefulness and limitations of various animal and cellular models of HD in uncovering molecular mechanisms of pathogenesis and developing novel therapies for HD.


Otogenic pneumococcal meningitis with pneumocephalus.
Streptococcus pneumoniae accounts for approximately 50% of bacterial meningitis cases in the United States annually. Since the advent of antibiotics, pneumococcal meningitis as a complication of a primary otogenic focus has been rare in the United States. The widespread use of immunosuppressants and increasing bacterial resistance to commonly prescribed antibiotics may contribute to a higher incidence of complications of otitis media in the future, similar to that of the pre-antibiotic era. We report a case of otogenic pneumococcal meningitis with pneumocephalus in an adult male on chronic immunosuppressant therapy. A 33-year-old man with Crohn's disease and azathioprine use presented to our Emergency Department with progressive headache while taking antibiotics for otitis media. Initial computed tomography scan of the brain revealed pneumocephaly, and cerebrospinal fluid analysis and culture diagnosed pneumococcal meningitis. The patient continued to have fevers while receiving intravenous antibiotics and underwent bilateral myringotomies; his clinical course subsequently improved significantly. Meningitis is a rare complication of Streptococcus pneumoniae infections since the advent of antibiotics; however, it may become more frequent with increasing antibiotic resistance and a growing population of immunocompromised patients. Additionally, pneumocephalus in the setting of meningitis and otitis media should raise the suspicion for mastoiditis (even without overt clinical findings) and early consultation with an otolaryngologist is warranted.


Persistent polyclonal B-cell lymphocytosis.
We present a case of persistent polyclonal B-cell lymphocytosis (PPBL). This syndrome is characterized by a persistent lymphocytosis with circulating atypical binucleated lymphocytes. The patient had serological evidence of a previous EBV infection, had raised polyclonal serum IgM levels and was a heavy smoker. No malignancy was detected.


Default Mode Network Engagement Beyond Self-Referential Internal Mentation.
The default mode network (DMN) is typically associated with off-task internal mentation, or with goal-oriented tasks that require self-referential processing such as autobiographical planning. However, recent reports suggest a broader involvement of the DMN in higher cognition. In line with this view, we report global connectivity changes that are centered on the main DMN hubs of precuneus and posterior cingulate cortex during a functional magnetic resonance imaging-based visuospatial version of the Tower of London planning task. Importantly, functional connectivity of these regions with the left caudate shows a significant relationship with faster reaction time to correct responses only during the high-demand planning condition, thus offering further evidence for the DMN's engagement during visuospatial planning. The results of this study not only provide robust evidence against the widely held notion of DMN disengagement during goal-oriented, attention-demanding, externally directed tasks but also support its involvement in a broader cognitive context with a memory-related role that extends beyond self-referential, internally directed mentation.


Radiology of cardiac devices and their complications.
This article familiarizes the reader with several different cardiac devices including pacemakers and implantable cardioverter defibrillators, intra-aortic balloon pumps, ventricular assist devices, valve replacements and repairs, shunt-occluding devices and passive constraint devices. Many cardiac devices are routinely encountered in clinical practice. Other devices are in the early stages of development, but circumstances suggest that they too will become commonly found. The radiologist must be familiar with these devices and their complications.


Prevalence of drug resistance and associated mutations in a population of Hiv-1+ Puerto Ricans in 2005.
This is a continuation of our efforts to maintain a record of the evolution of HIV-1 infection in Puerto Rico by monitoring the expression levels of antiretroviral resistance-associated mutations. Samples from 2005 were analyzed (458: 270 males, 137 females, 51 anonymous), using the TRUGENE HIV-1 Genotyping Kit and the OpenGene DNA Sequencing System. Results show that 60.1% of males and 50.2% of females had HIV-1 with resistance to at least one medication. The average number of HIV mutations in males was 6.27, while the average number of HIV mutations in females was 5.49. The highest levels of resistance were to Zalcitabine, Lamivudine, and Stavudine. The reverse transcriptase mutations with the highest frequency of expression were M184V, K103N and D67N. Protease mutations with the highest rate of expression were L63P, M361 and L90M. Significant differences between men and women were recorded in the levels of HIV-1 expressed mutations and resistance.


TTF-1 expression in pulmonary adenocarcinomas.
Tissue-specific gene expression is mediated largely by transcription factors, and a master regulatory gene is thus a potential marker of cellular lineage. Using normal fetal through adult pulmonary tissues and 64 consecutive lung adenocarcinomas, we examined the expression of thyroid transcription factor (TTF-1), which plays a crucial role in normal lung function and morphogenesis. TTF-1 was expressed consistently throughout the life stages and uniformly in the terminal respiratory unit, which is comprised of peripheral airway cells and small-sized bronchioles. Furthermore, the expression was maintained in 72% of adenocarcinomas that exhibited high correlation with surfactant apoprotein (p <0.001) and morphologic resemblance to terminal respiratory unit cells (p <0.001). The staining pattern was also uniform in the adenocarcinomas despite histologic and microenvironmental diversity in individual tumors and their metastatic foci. This consistency and uniformity, therefore, suggested that TTF-1 expression could be used as a lineage marker of terminal respiratory unit. We also identified interesting distinctions between TTF-1-positive and -negative adenocarcinomas based on their clinicopathologic features and expression of various cancer-associated genes. TTF-1-positive adenocarcinomas had statistically significant prevalence of female (p <0.01), nonsmoker (p <0.05), negative p53 staining (p <0.01), less frequent RB loss (p <0.05), and preserved expression of p27 (p <0.01). The results supported the TTF-1 lineage marker and suggested that molecular pathogenesis may in part be characterized by cellular lineage.


From trash to treasure: the role of bacterial extracellular vesicles in gut health and disease.
Bacterial extracellular vesicles (BEVs) have emerged as critical factors involved in gut health regulation, transcending their traditional roles as byproducts of bacterial metabolism. These vesicles function as cargo carriers and contribute to various aspects of intestinal homeostasis, including microbial balance, antimicrobial peptide secretion, physical barrier integrity, and immune system activation. Therefore, any imbalance in BEV production can cause several gut-related issues including intestinal infection, inflammatory bowel disease, metabolic dysregulation, and even cancer. BEVs derived from beneficial or commensal bacteria can act as potent immune regulators and have been implicated in maintaining gut health. They also show promise for future clinical applications in vaccine development and tumor immunotherapy. This review examines the multifaceted role of BEVs in gut health and disease, and also delves into future research directions and potential applications.


The MINT Sprint 2.0: A picture naming test for detection of naming impairments in Alzheimer's disease and in preclinical AD.
Evidence on the onset of naming deficits in Alzheimer's disease (AD) is mixed. Some studies showed an early decline, but others did not. The present study introduces evidence from a novel naming test. Cognitively normal (n = 138), mild cognitive impairment (MCI; n = 21), and Alzheimer's disease (AD; n = 31) groups completed an expanded Multilingual Naming Test with a time-pressured administration procedure (MINT Sprint 2.0). Cerebrospinal fluid biomarkers classified participants as true controls (n = 61) or preclinical AD (n = 26). Total correct MINT Sprint 2.0 scores exhibited good sensitivity and specificity (>0.85) for discriminating true controls from cognitively impaired (MCI/AD) groups and showed significant differences between true controls and preclinical AD groups. Time measurement did not improve classification, but percent resolved scores exhibited promise as an independent AD marker. Naming deficits can be detected in the earliest stages of AD with tests and procedures designed for this purpose.


Secukinumab improves psoriasis symptoms in patients with inadequate response to cyclosporine A: A prospective study to evaluate direct switch.
There are limited data on the safety and efficacy of switching to secukinumab from cyclosporine A (CyA) in patients with psoriasis. The purpose of the present study was to assess the efficacy and safety of secukinumab for 16 weeks after direct switching from CyA in patients with moderate-to-severe psoriasis. In this multicenter, open-label, phase IV study, 34 patients with moderate-to-severe psoriasis and inadequate response to CyA received secukinumab 300 mg s.c. at baseline and weeks 1, 2, 3, 4, 8 and 12. The primary end-point was ≥75% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75) at week 16. The efficacy of secukinumab treatment was evaluated up to week 16, and adverse events (AE) were monitored during the study. The primary end-point of the PASI 75 response at week 16 was achieved by 82.4% (n = 28) of patients receiving secukinumab. Early improvements were observed with secukinumab, with PASI 50 response of 41.2% at week 2 and PASI 75 response of 44.1% at week 4. AE were observed in 70.6% (n = 24) of patients, and there were no serious AE or deaths reported in the entire study period. Secukinumab showed a favorable safety profile consistent with previous data with no new or unexpected safety signals. The results of the present study show that secukinumab is effective in patients with psoriasis enabling a smooth and safe direct switch from CyA to biological therapy.


Headspace passive dosing of volatile hydrophobic chemicals - Aquatic toxicity testing exactly at the saturation level.
It is challenging to conduct aquatic tests with highly hydrophobic and volatile chemicals while avoiding substantial sorptive and evaporative losses. A simple and versatile headspace passive dosing (HS-PD) method was thus developed for such chemicals: The pure liquid test chemical was added to a glass insert, which was then placed with the open end in the headspace of a closed test system containing aqueous test medium. The test chemical served as the dominating partitioning donor for establishing and maintaining maximum exposure levels in the headspace and aqueous solution, without direct contact between the donor and the test medium. The HS-PD method was cross validated against passive dosing with a saturated silicone elastomer, using headspace gas chromatography as analytical instrument and saturated vapors as reference. The HS-PD method was then applied to control the exposure in algal growth inhibition tests with the green algae Raphidocelis subcapitata. The model chemicals were C9-C14 n-alkanes and the cyclic volatile methyl siloxanes octamethyltetracyclosiloxane (D4) and decamethylpentacyclosiloxane (D5). Growth rate inhibition at the solubility limit was 100% for C9-C13 n-alkanes and 53 ± 31% (95% CI) for tetradecane. A moderate inhibition of 11 ± 4% (95% CI) was observed for D4, whereas no inhibition was observed for D5. The present study introduces an effective method for aquatic toxicity testing of a difficult-to-test group of chemicals and provides an improved experimental basis for investigating toxicity cut-offs.


Natural killer cells activated by MHC class I(low) targets prime dendritic cells to induce protective CD8 T cell responses.
Conserved molecular patterns derived from pathogenic microorganisms prime antigen-presenting dendritic cells (DC) to induce adaptive T cell responses. In contrast, virus-infected or tumor cells that express low levels of major histocompatibility complex (MHC) class I activate natural killer (NK) cells for direct killing. It is unknown whether NK cell recognition of MHC class I(low) targets can also induce adaptive T cell responses. Here, we show that MHC class I(low) targets initiate a cascade of immune responses, starting with the immediate activation of NK cells. The activated NK cells then prime DC to produce IL-12 and to induce highly protective CD8 T cell memory responses. Therefore, sensing of MHC class I(low) targets by NK cells can link innate and adaptive immunity to induce protective T cell responses and may alarm the immune system during early infection with noncytopathic viruses.


Pulsatile drug release from an insoluble capsule body controlled by an erodible plug.
The objective of this study was to develop and evaluate a pulsatile drug delivery system based on an impermeable capsule body filled with drug and an erodible plug placed in the opening of the capsule body. The erodible plugs were either prepared by direct compression followed by placing the tablets in the capsule opening or by congealing a meltable plug material directly within the capsule opening. The disintegration/erosion properties of these plugs were determined and optimized for the final delivery system. In order to assure rapid drug release of the capsule content after erosion of the plug, various excipients (fillers, effervescent agents) and drugs with different solubilities were evaluated. The lag time prior to drug release and the subsequent drug release were investigated as function of capsule content, plug composition, plug preparation technique, plug hardness, weight, and thickness. The erosion time of the compressed plugs increased with increasing molecular weight of the hydrophilic polymer (e.g. hydroxypropyl methylcellulose, polyethylene oxide), decreasing filler (lactose) content and decreased with congealable lipidic plugs with increasing HLB-value and inclusion on surfactants. For complete and rapid release of the drug from the capsule body, effervescent agents had to be included in the capsule content. The drug delivery system showed typical pulsatile release profiles with a lag time followed by a rapid release phase. The lag time prior to the pulsatile drug release correlated well with the erosion properties of the plugs and, besides the composition of the plug, could be controlled by the thickness (weight) of the plug. A single-unit, capsular-shaped pulsatile drug delivery system was developed wherein the pulsatile release was controlled by the erosion properties of a compressed or congealed plug placed within the opening of the capsule opening.


Spatial and temporal association of As and Fe species on aquatic plant roots.
The formation of an Fe(III) precipitate (plaque) on the surface of aquatic plant roots may provide a means of attenuation and external exclusion of metals. Presently, the mechanisms of metal(loid) sequestration at the root surface are unresolved. Accordingly, we investigated the mechanisms of Fe and As attenuation and association on the roots of two common aquatic plant species, Phalaris arundinacea (reed canarygrass) and Typha latifolia (cattail) using X-ray absorption spectroscopy and X-ray fluorescence microtomography. Iron plaque of both P. arundinacea and T. latifolia consist predominantly of hydrated iron oxides (ferrihydrite) with lesser amounts of goethite and minor levels of siderite. Typha latifolia, however, differs from P. arundinacea by having a significant contribution from lepidocrocite as well as a greater proportion of crystalline minerals. Coexistence of goethite and lepidocrocite suggests the presence of chemically diverse microenvironments at the root surface. Arsenic exists as a combination of two sorbed As species, being comprised predominantly of arsenate- (approximately 82%) with lesser amounts (approximately 18%) of As(III)-iron (hydr)oxide complexes. Furthermore, both spatial and temporal correlations between As and Fe on the root surfaces were observed. While the iron (hydr)oxide deposits form a continuous surficial rind around the root, As exists in isolated regions on the exterior and interior of the root. Root surface-associated As generally corresponds to regions of enhanced Fe levels and may therefore occur as a direct consequence of Fe phase heterogeneity and preferential As sorption reactions.


A new nonempirical tuning scheme with single self-consistent field calculation: Comparison with global and IP-tuned range-separated functional.
System-dependent nonempirical tuning of range-separated functional provides a way to minimize the delocalization error of the system. However, existing nonempirical tuning method requires the computation of several ΔSCF calculations to determine the optimal μ value. In this article, we have defined a scheme to evaluate the optimal μ value with single self-consistent field calculation. Our method is based on the evaluation of the spherically symmetric average Electron localization function (ELF) region. According to this scheme, the radius of the spherically symmetric average ELF region gives is a measure of the distance at which the long-range part of the range-separated functional becomes dominant. Numerical results indicate that our method improves the reproduction of HOMO energies and HOMO-LUMO gap in comparison to global and IP-tuned range-separated functional. Moreover, in case of HOMO energies, maximum error of the ELF-tuned functional is considerably smaller than the global and IP-tuned functional. Furthermore, our method gives considerably smaller deviation of HOMO energies from ΔSCF IP than global range-separated functional. © 2017 Wiley Periodicals, Inc.


Effects of information on college students' perceptions of antidepressant medication.
The authors examined the impact of pharmaceutical companies' advertisements on college students' perceptions of depression and concomitant treatment with antidepressants among 13 male and 31 female undergraduates from a midwestern university. The students were randomly assigned to groups that read either pharmaceutical company advertisements or scientific information about depression and its treatment. The analysis revealed that 40% of the women in the advertisement condition as opposed to 1 woman (6%) in the scientific condition rated themselves as having mild, moderate, or severe depression on the Beck Depression Inventory, second edition. Women in the advertisement condition were significantly more likely to believe that depression required treatment with antidepressant medication and were more willing than women in the scientific condition to suggest antidepressant treatment to others.


Regio- and Diastereoselective and Enantiospecific Metal-Free C(sp(3) )-H Arylation: Facile Access to Optically Active 5-Aryl 2,5-Disubstituted Pyrrolidines.
Optically active 5-aryl 2,5-disubstituted pyrrolidines are the principal structural moiety of many bioactive compounds including natural products and catalysts for asymmetric synthesis. A highly regio- and diastereoselective and enantiospecific method for direct C-H arylation of aliphatic amine has been developed. Structurally diverse enantiopure arylated pyrrolidines were synthesized from commercially available starting materials, through a single-step three-component reaction under metal- and oxidant-free conditions. Furthermore, the complex analogous structure of CCK antagonist RP 66803 and angiotensin-converting enzyme inhibitors was easily constructed using the synthesized arylated pyrrolidine derivative. Detailed theoretical calculations (M06-2X/TZVPP/SMD//M06-2X/6-31+G(d,p) level) were also carried to investigate the mechanism and high level of stereocontrol involved in this direct sp(3) C-H arylation reaction. Preference for a given regio- and stereoselectivity in the arylated product can be explained through elucidation of the mechanism for dehydration, generating azomethine ylide, and for the final re-aromatization step. The calculated energies reveals that the re-aromatization step is essentially rate determining, accompanying an activation barrier of Δ(≠) G=25.6 kcal mol(-1) .


Circulating microRNA as a marker for predicting liver disease progression in patients with chronic hepatitis B.
Hepatitis B virus (HBV) constitutes an important risk factor for cirrhosis and hepatocellular carcinoma (HCC). The link between circulating microRNAs and HBV has been previously reported, although not as a marker of liver disease progression in chronic hepatitis B (CHB). The aim of this study was to characterize miRNA expression profiles between CHB with and without cirrhosis or HCC. A total of 12 subjects were recruited in this study. We employed an Affymetrix Gene Chip miRNA 3.0 Array to provide universal miRNA coverage. We compared microRNA expression profiles between CHB with and without cirrhosis/HCC to discover possible prognostic markers associated with the progression of CHB. Our results indicated 8 differently expressed microRNAs, of which miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, and miRNA-3200 were up-regulated, whereas miRNA-182 and miRNA-4485 were down-regulated in patients with CHB who progressed to cirrhosis/HCC as compared to those without progression. We demonstrated the differential expression of miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, miRNA-3200, miRNA-182, and miRNA-4485 between patients with HBV without cirrhosis/HCC and those who had progressed to these more severe conditions. These miRNAs may serve as novel and non-invasive prognostic markers for early detection of CHB-infected patients who are at risk of progression to cirrhosis and/or HCC.


Successful pregnancy after vaginal cancer treated with interferon.
A 25-year-old white woman with a vaginal invasive epidermal carcinoma was treated with interferon-alpha 2b (3,000,000 U intralesional, every two days for a total of 18 applications). Follow-up with Papanicolaou and colposcopy showed complete regression of the vaginal lesion, After three years the patient got pregnant. The prenatal course was uneventful and a vaginal delivery was performed. She is currently in follow-up without any signs of recurrence.


Rational design and synthesis of an orally bioavailable peptide guided by NMR amide temperature coefficients.
Enhancing the oral bioavailability of peptide drug leads is a major challenge in drug design. As such, methods to address this challenge are highly sought after by the pharmaceutical industry. Here, we propose a strategy to identify appropriate amides for N-methylation using temperature coefficients measured by NMR to identify exposed amides in cyclic peptides. N-methylation effectively caps these amides, modifying the overall solvation properties of the peptides and making them more membrane permeable. The approach for identifying sites for N-methylation is a rapid alternative to the elucidation of 3D structures of peptide drug leads, which has been a commonly used structure-guided approach in the past. Five leucine-rich peptide scaffolds are reported with selectively designed N-methylated derivatives. In vitro membrane permeability was assessed by parallel artificial membrane permeability assay and Caco-2 assay. The most promising N-methylated peptide was then tested in vivo. Here we report a novel peptide (15), which displayed an oral bioavailability of 33% in a rat model, thus validating the design approach. We show that this approach can also be used to explain the notable increase in oral bioavailability of a somatostatin analog.


Cerebrospinal Fluid Rhinorrhea and Subsequent Bacterial Meningitis due to an Atypical Clival Fracture.
Cases of cerebrospinal fluid (CSF) rhinorrhea due to clival fracture are rare. We present a case of bacterial meningitis with CSF rhinorrhea after a clival fracture. Heavily T2-weighted images showed a bone flap in the thinned clivus and fluid collection in the sphenoid sinus. CSF rhinorrhea developed at 1 month after mild trauma. The fracture may have been caused by the trauma and/or by the pressure gradient between the intracranial CSF space and the sphenoid sinus. A detailed history to identify trauma and an examination to detect bone defects in the skull base are necessary when patients present with bacterial meningitis and persistent rhinorrhea.


Routes to research for novice undergraduate neuroscientists.
Undergraduate students may be attracted to science and retained in science by engaging in laboratory research. Experience as an apprentice in a scientist's laboratory can be effective in this regard, but the pool of willing scientists is sometimes limited and sustained contact between students and faculty is sometimes minimal. We report outcomes from two different models of a summer neuroscience research program: an Apprenticeship Model (AM) in which individual students joined established research laboratories, and a Collaborative Learning Model (CLM) in which teams of students worked through a guided curriculum and then conducted independent experimentation. Assessed outcomes included attitudes toward science, attitudes toward neuroscience, confidence with neuroscience concepts, and confidence with science skills, measured via pre-, mid-, and postprogram surveys. Both models elevated attitudes toward neuroscience, confidence with neuroscience concepts, and confidence with science skills, but neither model altered attitudes toward science. Consistent with the CLM design emphasizing independent experimentation, only CLM participants reported elevated ability to design experiments. The present data comprise the first of five yearly analyses on this cohort of participants; long-term follow-up will determine whether the two program models are equally effective routes to research or other science-related careers for novice undergraduate neuroscientists.


GenIO: a phenotype-genotype analysis web server for clinical genomics of rare diseases.
GenIO is a novel web-server, designed to assist clinical genomics researchers and medical doctors in the diagnostic process of rare genetic diseases. The tool identifies the most probable variants causing a rare disease, using the genomic and clinical information provided by a medical practitioner. Variants identified in a whole-genome, whole-exome or target sequencing studies are annotated, classified and filtered by clinical significance. Candidate genes associated with the patient's symptoms, suspected disease and complementary findings are identified to obtain a small manageable number of the most probable recessive and dominant candidate gene variants associated with the rare disease case. Additionally, following the American College of Medical Genetics and Genomics and the Association of Molecular Pathology (ACMG-AMP) guidelines and recommendations, all potentially pathogenic variants that might be contributing to disease and secondary findings are identified. A retrospective study was performed on 40 patients with a diagnostic rate of 40%. All the known genes that were previously considered as disease causing were correctly identified in the final inherit model output lists. In previously undiagnosed cases, we had no additional yield. This unique, intuitive and user-friendly tool to assists medical doctors in the clinical genomics diagnostic process is openly available at https://bioinformatics.ibioba-mpsp-conicet.gov.ar/GenIO/ .


[The relationship between the post-rhinoplastic functional disorders, the surgical approach and techniques, the magnitude and extent of the intervention].
The objective of the present study was to investigate the functional consequences of aesthetic rhinoplasty. The authors compared the results of corrective surgery depending on the surgical approach, the extent of the intervention, and the operative techniques employed based on large enough set of clinical observations obtained during the treatment of 253 patients. It was shown that the post-rhinoplastic difficulties in nasal breathing experienced by some patients occurred significantly more frequently after the use of the «endonasal» surgical approach than following «open» rhinoplasty (75% vs 68%). The functional outcome of the intervention was much better in the case of single-step rhinoseptoplasty than after the intranasal intervention (turbinoplasty, sinusotomy) based on the results of objective assessment (the total volumetric flow (TVF) 629±98 cub. cm/s and 397±65 cub. cm/s respectively; p<0.05). It is concluded that the application of the structure-sparing tools during primary rhinoplasty, such as expandable grafts, extending flaps, and restorative transplants, can reduce the severity and the frequency of the functional disorders likely to develop during the long-term follow-up (TVF 550±85 cub. cm/s vs 303±50 cub. cm/s; p<0.05).


The embodied mind in motion: a neuroscientific and philosophical perspective on prevention and therapy of dementia.
The embodied mind in motion is a concept in which health and well-being, prevention and therapy, as well as lifestyle and habits meet. The mind changes profoundly in the course of dementias, affecting daily living and resulting in reduced quality of life. Interdisciplinary approaches are required for a holistic understanding of how the mind is affected by dementia. We here explore what such a holistic theory of dementia might look like and propose the idea of "embodied mind in motion". The paradigm is biopsychosocial or biocultural, the theoretical anchor point is the lifeworld, and the guiding concept is "embodiment," as body and mind are constantly in motion. Physical activity is, hence, central for the experience of health and well-being, beyond being "exercise" and "health behavior". We discuss the embodied mind in motion referring to phenomenology, enactivism and (philosophical) anthropology. In our view, habits are embodied long-term memories and a philosophical equivalent to lifestyle. They unfold the meaningfulness of moving the body, complementing the objectifiable benefits of physical exercise. Empirical studies on "holistic activities" like hiking, yoga, music and dance illustrate improved integration into everyday life. Their meaningfulness enhances compliance and increases the preventive and even therapeutic potential. A crucial factor for this is the emotional dimension of lifestyle, exemplified by the virally popularized performance of "Swan Lake" by wheel-chair bound ex-ballerina Marta Cinta González Saldaña, suffering from Alzheimer's disease. A number of epistemological and ontological consequences anchor "embodied movement" as a valuable principle for dementia research.


Multiplex PCR for the detection of genes encoding aminoglycoside modifying enzymes and methicillin resistance among Staphylococcus species.
We developed multiplex polymerase chain reaction (PCR) to detect aac(6 ')/aph(2 "), aph(3 ')-IIIa, and ant(4 ')-Ia, the genes encoding the most clinically relevant amino-glycoside modifying enzymes (AME), and simultaneously, the methicillin resistant gene, mecA, in Staphylococcus species. Clinical isolates of 45 S. aureus and 47 coagulase negative staphylococci (CNS) from tertiary university hospitals were tested by conventional susceptibility testing, using the agar dilution method and by multiplex PCR. Of a total of 92 isolates, 61 isolates were found to be methicillin-resistant. Of these, 54 isolates (89%) were found to be harboring mecA. Seventy-five percent of the 92 isolates demonstrated resistance to at least one of the aminoglycosides tested. Moreover, resistance to aminoglycosides was closely associated with methicillin-resistance (p<0.05). The most prevalent AME gene was aac(6 ')/aph(2 ") which was found in 65% of the isolates, and ant(4 ')-Ia and aph(3 ')-IIIa were present in 41% and 9% of the isolates, respectively. The concordance between methicillin-resistance and the presence of mecA gene was 98% in S. aureus and 81% in CNS. The concordance between gentamicin resistance and the presence of aac(6 ')/aph(2 ") gene was 100% in S. aureus and 85% in CNS. The multiplex PCR method that we developed appears to be both a more rapid and reliable than conventional method.


Familial transmission of panic disorder: effect of major depression comorbidity.
This study assesses the effect of major depressive disorder (MDD) comorbidity on familial transmission of panic disorder (PD). The following questions are addressed: (1) is PD familial, i.e., do relatives of patients with PD show an increased risk for PD? (2) do PD and MDD share a common diathesis, i.e., do relatives of patients with PD without MDD show an increased risk for MDD? (3) is lifetime comorbid PD with MDD conjointly familial, i.e., do relatives of patients with PD and MDD show an increased risk for the combined syndrome? Subjects were: (1) 152 relatives of 54 anxiety clinic patients with PD and MDD; (2) 193 relatives of 72 patients with PD without MDD; (3) 231 relatives of 77 not ill controls. Relatives were interviewed by clinicians, and best estimate DSM-III-R diagnoses were formulated by senior staff. Relatives of PD with MDD (13%) and PD without MDD probands (9%) showed significantly higher rates of PD than relatives of controls (3%). Relatives of PD with MDD probands (37%) showed significantly higher rates of MDD than relatives of PD without MDD (24%) and controls (21%), with no difference between the latter two groups. Relatives of PD with MDD probands (9%) showed significantly higher rates of PD with MDD than relatives of PD without MDD (3%) and controls (1%). We conclude that: (1) PD is familial; (2) PD in the absence of MDD does not incur increased risk of MDD to relatives; and (3) PD with MDD may represent a distinct, complex syndrome.


Oral assessment of children with an autism spectrum disorder.
The study assessed the oral health status of children with an autism spectrum disorder (ASD) to help establish the oral health needs of this population. Oral assessments were conducted on 39 children with an ASD and 16 children with other developmental disabilities (DD), solicited from 3 different schools. Conditions assessed were bacterial plaque, gingivitis, dental caries, restorations, bruxism, delayed eruption/missing teeth, oral infection, developmental anomalies, injuries, occlusion, salivary flow, and oral defensiveness. Chi-square and Fisher's exact test of significance were used to compare groups. Young children with an ASD who resided with parents showed significantly more signs of bruxism than the comparison groups. Likewise, older children who lived at the residential school manifested significantly more gingivitis. No other significant differences existed when age and residence were considered for children with an ASD. When comparing children with ASD to those with another DD, the latter group showed significantly more oral injuries, abnormal salivary flow, and developmental anomalies. Children with an ASD displayed the following percentages for clinically visible conditions: plaque (85%), gingivitis (62%), and caries (21%). Approximately half of the children with ASD were orally defensive. Children with an ASD appear to have oral conditions that might increase the risk of developing dental disease. The extent of risk is unclear and needs further investigation.


Characterization of variant Salmonella genomic island 1 multidrug resistance regions from serovars Typhimurium DT104 and Agona.
Strains of multidrug-resistant Salmonella enterica serovar Typhimurium DT104 (DT104) and S. enterica serovar Agona (Agona) have been found to harbor Salmonella genomic island 1 (SGI1), a 43-kb genomic region that contains many of the drug resistance genes. Such strains are resistant to ampicillin (pse-1), chloramphenicol/florfenicol (floR), streptomycin/spectinomycin (aadA2), sulfonamides (sul1), and tetracycline [tet(G)] (commonly called the ACSSuT phenotype). All five resistance genes are found in a 13-kb multidrug resistance (MDR) region consisting of an unusual class I integron structure related to In4. We examined DT104 and Agona strains that exhibited other resistance phenotypes to determine if the resistance genes were associated with variant SGI1 MDR regions. All strains were found to harbor variant SGI1-like elements by using a combination of Southern hybridization, PCR mapping, and sequencing. Variant SGI1-like elements were found with MDR regions consisting of (i) an integron consisting of the SGI1 MDR region with the addition of a region containing a putative transposase gene (orf513) and dfrA10 located between duplicated qacEDelta1/sulI genes (SGI1-A; ACSSuTTm); (ii) an integron with either an aadA2 (SSu) or a pse-1 (ASu) cassette (SGI1-C and SGI1-B, respectively); (iii) an integron consisting of the SGI1-C MDR region plus an orf513/dfrA10 region as in SGI1-A (SGI1-D; ASSuTm; ampicillin resistance due to a TEM beta-lactamase); and (iv) an integron related to that in SGI1 but which contains a 10-kb inversion between two copies of IS6100, one which is inserted in floR (SGI1-E; ASSuT). We hypothesize that the MDR of SGI1 is subject to recombinational events that lead to the various resistance phenotypes in the Salmonella strains in which it is found.


Development and validation of a robotic multifactorial fall-risk predictive model: A one-year prospective study in community-dwelling older adults.
Falls in the elderly are a major public health concern because of their high incidence, the involvement of many risk factors, the considerable post-fall morbidity and mortality, and the health-related and social costs. Given that many falls are preventable, the early identification of older adults at risk of falling is crucial in order to develop tailored interventions to prevent such falls. To date, however, the fall-risk assessment tools currently used in the elderly have not shown sufficiently high predictive validity to distinguish between subjects at high and low fall risk. Consequently, predicting the risk of falling remains an unsolved issue in geriatric medicine. This one-year prospective study aims to develop and validate, by means of a cross-validation method, a multifactorial fall-risk model based on clinical and robotic parameters in older adults. Community-dwelling subjects aged ≥ 65 years were enrolled. At the baseline, all subjects were evaluated for history of falling and number of drugs taken daily, and their gait and balance were evaluated by means of the Timed "Up & Go" test (TUG), Gait Speed (GS), Short Physical Performance Battery (SPPB) and Performance-Oriented Mobility Assessment (POMA). They also underwent robotic assessment by means of the hunova robotic device to evaluate the various components of balance. All subjects were followed up for one-year and the number of falls was recorded. The models that best predicted falls-on the basis of: i) only clinical parameters; ii) only robotic parameters; iii) clinical plus robotic parameters-were identified by means of a cross-validation method. Of the 100 subjects initially enrolled, 96 (62 females, mean age 77.17±.49 years) completed the follow-up and were included. Within one year, 32 participants (33%) experienced at least one fall ("fallers"), while 64 (67%) did not ("non-fallers"). The best classifier model to emerge from cross-validated fall-risk estimation included eight clinical variables (age, sex, history of falling in the previous 12 months, TUG, Tinetti, SPPB, Low GS, number of drugs) and 20 robotic parameters, and displayed an area under the receiver operator characteristic (ROC) curve of 0.81 (95% CI: 0.72-0.90). Notably, the model that included only three of these clinical variables (age, history of falls and low GS) plus the robotic parameters showed similar accuracy (ROC AUC 0.80, 95% CI: 0.71-0.89). In comparison with the best classifier model that comprised only clinical parameters (ROC AUC: 0.67; 95% CI: 0.55-0.79), both models performed better in predicting fall risk, with an estimated Net Reclassification Improvement (NRI) of 0.30 and 0.31 (p = 0.02), respectively, and an estimated Integrated Discrimination Improvement (IDI) of 0.32 and 0.27 (p<0.001), respectively. The best model that comprised only robotic parameters (the 20 parameters identified in the final model) achieved a better performance than the clinical parameters alone, but worse than the combination of both clinical and robotic variables (ROC AUC: 0.73, 95% CI 0.63-0.83). A multifactorial fall-risk assessment that includes clinical and hunova robotic variables significantly improves the accuracy of predicting the risk of falling in community-dwelling older people. Our data suggest that combining clinical and robotic assessments can more accurately identify older people at high risk of falls, thereby enabling personalized fall-prevention interventions to be undertaken.


Changing role of endoscopy in the new millennium. Bushell Lecture, Asia-Pacific Digestive Week 2001.
Endoscopy has confronted many challenges, including serology tests for Helicobacter pylori, virtual colonoscopy and magnetic resonance cholangiopancreatography. These new modalities might eventually replace endoscopy in diagnosing digestive tract diseases. New advancements such as capsule endoscopy, infrared spectroscopy, optical coherent tomography, and various therapeutic procedures have opened new horizons in the field. Endoscopists should keep their mind open and be prepared for the changing role of endoscopy in the new millennium.


Cannabinoid agonists and antagonists modulate lithium-induced conditioned gaping in rats.
Considerable evidence indicates that conditioned gaping in rats reflects nausea in this species that does not vomit. A series of experiments evaluated the potential of psychoactive cannabinoid agonists, delta-9-THC and HU-210, and non-psychoactive cannabinoids, Cannabidiol (CBD) and its dimethylheptyl homolog (CBD-dmh), to interfere with the establishment and the expression of conditioned gaping in rats. All agents attenuated both the establishment and the expression of conditioned gaping. Furthermore, the CB1 antagonist, SR-141716, reversed the suppressive effect of HU-210 on conditioned gaping. Finally, SR-141716 potentiated lithium-induced conditioned gaping, suggesting that the endogenous cannabinoid system plays a role in the control of nausea.


Species-dependent Clinical Findings of Malaria Caused by Various Plasmodia in an Endemic Area of Kerman Province, Southeastern Iran.
Malaria is a big problem of public health in many tropical countries where socioeconomic development is deficient. Four species of plasmodium are capable of infecting human: P. falciparum, P. malaria, P.vivax, P. ovale. Southeastern corner of Iran, including Sistan and Baluchestan, Hormozgan and the tropical part of Kerman Province, are endemic region of malaria. This study aimed to find out clinical findings in malaria caused by various plasmodium species in moderate transmission area of southern Kerman Province. This study was conducted in health centers of Kahnooj, Manujan, Ghale-Ganj, Roudbar and Fariab in south of Kerman Province, Southeastern Iran during 2005-2009. Three hundred and thirty patients with positive malaria parasite slides entered the study. Frequencies of several malaria clinical presentations were investigated in four plasmodium species. 54.2% of considered patients were male. Mean age of patients was 22.8±17.8 yr. Younger and older patient were 6 months and 80 yr, respectively. Ten patients were infected with P. falciparum, 314 with plasmodium vivax and 6 with mixed infection. The symptoms of fever, chills and sweating were present in 74.6% of subjects. Other complaints were joint pain, headache, fatigue, vomiting, and diarrhea. Splenomegaly was detected in 17.57% of the individuals. Malaria should be considered in differential diagnosis of all acutely febrile patients in endemic area. Classic symptoms of fever, chills and sweating may not present in all of patients.