MicroRNA-302b-3p Suppresses Cell Proliferation Through AKT Pathway by Targeting IGF-1R in Human Gastric Cancer.
MiR-302b is a major microRNA found in human embryonic stem cells and induced pluripotent stem cells. However, its function in gastric cancer progression remains unclear. Quantitative reverse transcription-PCR was performed to detect the expression levels of miR-302b-3p in gastric cancer tissues. MTT, colony formation, and flow cytometer analyses were conducted to explore the function of miR-302b-3p in MKN-45/SGC-7901 cells. A dual-luciferase reporter was used to validate the bioinformatics-predicted target gene of miR-302b-3p. Western blotting and RNA interference were used to evaluate the expression of the AKT signaling pathway and determine the mechanisms underlying miR-302b-3p-induced anti-tumor effects. MiR-302b-3p expression was decreased in gastric cancer tissues and cell lines. Enforced expression of miR-302b suppressed cell proliferation and cell cycle G1-S transition and induced apoptosis. IGF-1R was found to be a direct target of miR-302b-3p, and silencing of IGF-1R resulted in the same biological effects as those induced by miR-302b-3p overexpression in gastric cancer cells. Importantly, both overexpression of miR-302b-3p and silencing of IGF-1R decreased AKT phosphorylation, which modulated AKT related cell cycle regulators (cyclin A2, cyclin D1, CDK2, and CDk6) and apoptotic protein Bax/Bcl-2. These results indicate the tumor suppressor role of miR-302b-3p in the pathogenesis of gastric cancer.


RNA-Seq Analysis Discovers the Critical Role of Rel in ppGpp Synthesis, Pathogenicity, and the VBNC State of Clavibacter michiganensis.
The viable but nonculturable (VBNC) state is a unique survival strategy of bacteria in response to stress conditions. It was confirmed that Clavibacter michiganensis, the causal agent of bacterial canker in tomato, could be induced into the VBNC state by exposure to CuSO4 in an oligotrophic solution. RNA-sequencing analysis was used to monitor the mechanisms of the VBNC state during CuSO4 induction in C. michiganensis. The results identified that numerous genes involved in stringent response, copper resistance, and stress resistance were upregulated, and some involved in cell division were downregulated significantly. The study investigated the importance of Rel, which is an essential enzyme in the synthesis of the molecular alarmone ppGpp, via the generation of a Δrel mutant and its complementation strain. Biological characterization revealed that deficiency of rel reduced the bacterial growth, production of exopolysaccharides, and pathogenicity as well as ppGpp production. The Δrel mutant increased the sensitivity to environmental stress, exhibiting reduced growth on minimal media and a propensity to enter the VBNC state in response to CuSO4. These findings have important implications for the understanding of survival mechanism and management of C. michiganensis and other phytopathogenic bacteria.


Subjective complaints, verbal fluency, and working memory in mild multiple sclerosis.
Patients with mild multiple sclerosis (MS) regularly report subjective complaints characterized by generalized cognitive inefficiency. A feature of these complaints is reduced verbal fluency, for example, losing the thread of conversation. Mild MS patients and controls were compared on subjective complaints, verbal fluency, and working memory, and the possible role of working memory was investigated. As predicted, subjective difficulties and verbalfluency each correlated with working memory. Subjective difficulties and verbal fluency were also related. Within the control group, the subjective difficulties were associated only with depression. On the other hand, in the MS group, subjective difficulties were unrelated to affective state but were correlated with working memory. For the patients, partialing out depression and anxiety did not influence any of the correlations involving subjective difficulties, verbal fluency, or working memory. These findings support the proposal that working memory impairment underlies subjective complaints of mild MS patients and that verbal dysfluency is part and parcel of this phenomenon.


Recovery kinetics following eccentric exercise is volume-dependent.
The present study compared the effect of 75 vs 150 vs 300 intensity-matched eccentric contractions on muscle damage and performance recovery kinetics. Ten healthy males participated in a randomized, cross-over study consisted of 4 experimental trials (ECC75, ECC150, ECC300 and Control - no exercise) with a 4-week washout period in-between. Performance and muscle damage, inflammatory and oxidative stress markers were evaluated at baseline, post-exercise, 24, 48 and 192 hours following each exercise protocol. Concentric and eccentric peak torque decreased similarly in ECC150 and ECC300 during the first 48 h of recovery (p < 0.05) but remained unaffected in ECC75. Countermovement jump indices decreased post-exercise and at 24 h in ECC150 and ECC300, with ECC300 inducing a more pronounced reduction (p < 0.05). Creatine kinase increased until 48 h of recovery in all trials and remained elevated up to 192 h only in ECC300 (p < 0.05). Delayed onset of muscle soreness increased, and knee-joint range of motion decreased in a volume-dependent manner during the first 48 h (p < 0.05). Likewise, a volume-dependent decline of glutathione and a rise of protein carbonyls was observed during the first 48 h of recovery (p < 0.05). Collectively, our results indicate that muscle damage and performance recovery following eccentric exercise is volume dependent, at least in lower limbs.


Sugar-modified conjugated diene analogues of adenosine and uridine: synthesis, interaction with S-adenosyl-L-homocysteine hydrolase, and antiviral and cytostatic effects.
Moffatt oxidation of 2',3'-O-isopropylideneuridine (1a) and treatment of the crude 5'-aldehyde with formylmethylene-stabilized Wittig reagent gave the vinylogously extended 7'-aldehyde2a. Condensation of 2a with ethoxycarbonyl- or dibromomethylene phosphorane reagents gave the conjugated dienes 6a and 4a, respectively. Deacetonization gave diene ester 7a [5'(E),7'(E); with s-trans conformation] and dibromodiene 5a [5'(E)], respectively. Analogously, 2',3'-O-isopropylideneadenosine (1b) was Wittig-extended into the conjugated dibromodiene 5b [5'(E)] and dienoic ester 7b [5'(E),7'(E)]. Furthermore, palladium-catalyzed coupling of the vinyl 6'(E)-stannanes 14 with (E) and (Z) ethyl 3-iodoacrylate gave stereodefined access to dienoic esters 7 (E,E) and 16 (E,Z). Incubation of AdoHcy hydrolase with 100 microM of 5b resulted in partial inhibition of the enzyme without any apparent change in the enzyme's nicotinamide adenine dinucleoside (NAD(+)) content. In contrast, 7b and 16b produced time- and concentration-dependent inactivation of S-adenosyl-L-homocysteine (AdoHcy) hydrolase producing significant decreases in the enzyme's NAD(+) content. However, 7b and 16b upon incubation with AdoHcy hydrolase were not metabolized suggesting that these compounds are type I mechanism-based inhibitors. No specific antiviral activity was noted for 5a,b, 7a,b, and 16a,b against any of the viruses tested; dibromodiene 5b proved cytotoxic at a concentration > or =6.7 microM and cytostatic at > or =11 microM, while dienoic esters 16a,b showed activity against both varicella-zoster virus (at 10 microM, 16a) and cytomegalovirus (at 10 microM, 16a; 18 microM, 16b).


[Serotonin antagonism involved in the antipsychotic effect. Confirmation with ritanserine and risperidone].
Shortly after the introduction of the first neuroleptics a serotonin hypothesis of schizophrenia has been proposed. But neuroleptics in animals and in man were found to produce effects more consistently related to inhibition of the dopaminergic than of any other type of neurotransmission. However, two early neuroleptics, pipamperone and clozapine, act pharmacologically more on 5-HT2 than on D2 receptors. Both have a distinct clinical profile and low EPS liability. The development of selective 5-HT2-antagonists, devoid of LSD-like properties, resulted in a first compound, ritanserin. Clinically, the highly specific 5-HT2-antagonism of ritanserin improves dysthymia, increases slow wave sleep and supports classical neuroleptic treatment by decreasing negative symptoms and EPS. These properties, being valuable by themselves, have been associated to dopamine D2-antagonism in the new antipsychotic risperidone, which is an extremely potent 5-HT2-antagonist. At doses of 5 mg daily risperidone acts on both negative and positive symptoms of schizophrenia in the virtual absence of EPS.


A Metabolite Composite Score Attenuated a Substantial Portion of the Higher Mortality Risk Associated With Frailty Among Community-Dwelling Older Adults.
Frailty is more prevalent among black versus white older Americans. We previously identified 37 metabolites associated with the vigor to frailty spectrum using the Scale of Aging Vigor in Epidemiology (SAVE) among older black men from the Health, Aging, and Body Composition (Health ABC) study. Here, we sought to develop a metabolite composite score based on the 37 SAVE-associated metabolites and determine whether the composite score predicts mortality and whether it attenuates the association between frailty and mortality among older black men. Plasma metabolites were measured using liquid chromatography-mass spectrometry. Most of the 37 metabolites were organic acids/derivatives or lipids. Metabolites were ranked into tertiles: tertiles associated with more vigorous SAVE scores were scored 0, mid-tertiles were scored 1, and tertiles associated with frailer SAVE scores were scored 2. Composite scores were the sum of metabolite tertile scores. We examined mortality associations using Cox regression. Percent attenuation estimated the extent to which metabolites attenuated the association between frailty and mortality. One standard deviation frailer SAVE was associated with 30% higher mortality, adjusting for age and site (p = .0002); this association was attenuated by 56% after additionally adjusting for the metabolite composite score. In this model, one standard deviation higher metabolite composite score was associated with 46% higher mortality (p < .0001). Metabolite composite scores also predicted mortality (p = .045) in a validation sample of 120 older adults (40% men, 90% white). These metabolites may provide a deeper characterization of the higher mortality that is associated with frailty among older adults.


Role of the nurse in the design, delivery, monitoring and coordination of cancer survivorship care plans: An integrative review.
Survivorship care plans (SCPs) are recommended as a tool for the care of cancer survivors. SCPs have been implemented with a multidisciplinary approach; however, the specific role of nurses in the SCP is unknown. Our aim is to determine the role of nurses and their degree of participation in cancer SCPs. Integrative review of the literature with systematic methodology. PubMed, CINAHL, PsycINFO, Web of Science, Cochrane and Cancerlit databases were reviewed. Articles published up to March 2021 were included. Of the 2,638 publications identified, 22 studies met our inclusion criteria. Quality of included studies was assessed using Joanna Briggs Institute quality assessment tools. The studies showed that nurses play a key role and participate in different phases of the SCP, including design, delivery, monitoring and coordination among different levels of care, with varying degrees of involvement and responsibility; design and delivery of the SCP are the phases with the highest nurse participation (18 out of 22 studies). The majority of SCPs are implemented in specialized, hospital-based care and focus on short-term cancer survivors, who are actively undergoing oncological treatments. This review shows that nurses actively participate in the design, implementation and coordination of SCPs. However, SCPs focus on the acute survival and treatment phases, and there is a gap in their use in long-term cancer survivorship. This gap may be one reason the needs of long-term cancer survivors are not covered. This review contributes to the current body of knowledge by addressing the role of nurses in cancer SCPs. We recommend the involvement of an advanced practice nurse as SCP coordinator to improve communication between cancer specialists and primary care providers and to promote continued care throughout the different phases of cancer survivorship, including long-term survival.


Gender differences in older patient populations: a case linkage study of community health, mental health, and social services in the United Kingdom.
We identify gender differences in older health and social care populations by comparing the total population of older people with the total population of women and the total population of older women, respectively. We combine anonymised data across community health (CH; N = 82,751), mental health (MH; N = 19,029), and social care service (SC; N = 19,461) populations in one UK county (N = 496,863) over 3 years. Approximately two thirds of older care populations were female. In both single- and dual-agency care populations a profile emerged of older patients, female patients and older female patients, this profile varied across different diagnostic and care groups.


Development of methodologic tools for planning and managing library services. II. Measuring a library's capability for providing documents.
A method of measuring a library's capability for providing the documents its users need has been developed. The library is tested with a representative sample of such documents to determine how long would be required for users to obtain these documents. Test results are expressed in terms of a Capability Index, which has a maximal value of 100 only if all the sample documents are found "on shelf." Specific tests employing samples of 300 documents have been developed that are appropriate for academic and for "reservoir" biomedical libraries. Realistic field trials have demonstrated that these two tests are practical to administer and that test results are adequately reproducible. When strict comparability is not important, a library can test itself. In assessing a reservoir library, test results are supplemented by data on its typical processing time for interlibrary loan requests. Currently these tests are being used in a national survey. The general method is applicable to other types of libraries, provided appropriate test samples are established. If their limitations are clearly understood, these "Document Delivery Tests" can be valuable tools for planning and managing library services.


Transmission loss measurements and geoacoustic sensitivity modeling at 1.2 kHz.
The Shallow Water Experiment 2006 was conducted off the coast of New Jersey in the summer of 2006. Defence Research and Development Canada-Atlantic performed a series of experiments designed to validate the use of rapid environmental assessment tools and methods to improve active sonar performance predictions. The sensitivity of acoustic propagation to a varying or uncertain environment is determined by examining the relative change of acoustic pressure caused by environmental variability, using the method described recently [Dosso et al., J. Acoust. Soc. Am. 121, 42 (2007)]. The variability of the modeled environmental parameters is based on measured and estimated oceanographic and geoacoustic properties. The resulting sensitivity is compared to measured transmission loss data at 1.2 kHz.


Increased Risk of Chronic Sinusitis in Adults With Gastroesophgeal Reflux Disease: A Nationwide Population-Based Cohort Study.
Although gastroesophageal reflux disease (GERD) has been reported to coexist with chronic rhinosinusitis (CRS), it remains controversial whether it increases risk of CRS in adults. This study accesses risk of CRS in adults with newly diagnosed GERD. We identified 15,807 adult patients with newly diagnosed GERD from Taiwan's National Health Insurance Research Database for January 1, 2006 to December 31, 2009. We also randomly selected 47,421 subjects without this disease and matched them with patients by age, sex, index year, and comorbidity to create a control cohort. A Cox proportional hazards model was conducted to estimate the development of CRS, including CRS without nasal polyps and CRS with nasal polyps. Subjects were followed for a median of 2.12 years. In total, CRS developed in 964 (1.52%) of the subjects: 406 patients with GERD (2.57%) and 558 without it (1.18%). After adjustment, those with GERD were found to have a 2.36 times greater risk of CRS (95% confidence interval = 2.08-2.68; P < .001). Risk of this CRS without nasal polyps was higher than the disease with polyps (adjusted hazard ratio: 2.48 vs 1.85). The individuals with GERD in this study were at significantly greater risk of CRS, most often without nasal polyps.


Comparison of parametric and nonparametric methods to map oligogenes by linkage.
A sample of 95 sib pairs affected with insulin-dependent diabetes and typed with their normal parents for 28 markers on chromosome 6 has been analyzed by several methods. When appropriate parameters are efficiently estimated, a parametric model is equivalent to the beta model, which is superior to nonparametric alternatives both in single point tests (as found previously) and in multipoint tests. Theory is given for meta-analysis combined with allelic association, and problems that may be associated with errors of map location and/or marker typing are identified. Reducing by multipoint analysis the number of association tests in a dense map can give a 3-fold reduction in the critical lod, and therefore in the cost of positional cloning.


Overall function in rural childhood cancer survivors. The role of social competence and emotional health.
This study compared the functioning of 20 rural cancer survivors, aged 6 to 16 years, with that of 40 age- and gender-matched school peers. Social competence and emotional health were evaluated, along with academic performance and physical limitations. Eight measures were used: the teacher and parent Child Behavior Check Lists, the Health Resources Inventory, the Vineland Revised Scale of Social Maturity, the Piers-Harris Child's Self-Concept Scale, the Parcel and Meyers' Health Locus of Control, the Moos' Family Environment Scale, and the Functional Status II(r). Cancer survivors and controls had similar attitudes about self-esteem, family conflicts, physical functioning, social skills, independence, and sense of control over health. Both parents and teachers noted poorer social competence among the cancer survivors than among controls, but parents of survivors reported more behavior problems, whereas teachers stressed poorer school performance. Routine screening for emotional health, social competence, and academic performance should be part of the follow-up care of pediatric cancer survivors.


Simultaneous measurement of refractive index and temperature by integrating an external Fabry-Perot cavity with a fiber Bragg grating.
A fiber sensor for simultaneous measurements of refractive index and temperature based on the integration of a fiber Bragg grating (FBG) with an external Fabry-Perot (F-P) cavity is presented. The fringe contrast of the interference spectrum generated by the F-P cavity is used to determine the external refractive index, while the wavelength shift of the FBG is used to measure temperature. The result showed that the refractive index and temperature sensitivity for the integrated sensor is 8.1 × 10(-6) and 0.01006 nm/°C, respectively.


A Systematic Review of Areal Units and Adjacency Used in Bayesian Spatial and Spatio-Temporal Conditional Autoregressive Models in Health Research.
Advancements in Bayesian spatial and spatio-temporal modelling have been observed in recent years. Despite this, there are unresolved issues about the choice of appropriate spatial unit and adjacency matrix in disease mapping. There is limited systematic review evidence on this topic. This review aimed to address these problems. We searched seven databases to find published articles on this topic. A modified quality assessment tool was used to assess the quality of studies. A total of 52 studies were included, of which 26 (50.0%) were on infectious diseases, 10 (19.2%) on chronic diseases, 8 (15.5%) on maternal and child health, and 8 (15.5%) on other health-related outcomes. Only 6 studies reported the reasons for using the specified spatial unit, 8 (15.3%) studies conducted sensitivity analysis for prior selection, and 39 (75%) of the studies used Queen contiguity adjacency. This review highlights existing variation and limitations in the specification of Bayesian spatial and spatio-temporal models used in health research. We found that majority of the studies failed to report the rationale for the choice of spatial units, perform sensitivity analyses on the priors, or evaluate the choice of neighbourhood adjacency, all of which can potentially affect findings in their studies.


Acute Inflammatory Demyelinating Polyneuroradiculopathy with Ipilimumab in Metastatic Melanoma: A Case Report and Review of Literature.
Ipilimumab (Bristol-Myers Squibb Co., New York, NY) is a novel anticancer medication used for the treatment of metastatic melanoma. The exact mechanism of its action remains unclear; however, data from previous clinical trials postulates the immunomodulatory activity of ipilimumab to enhance therapeutic effectiveness. Ipilimumab was approved by the Food and Drug Administration (FDA) in March 2011 for use in stage III and IV of unresectable metastatic melanoma. We report a single case of acute inflammatory demyelinating polyneuroradiculopthy (AIDP) in the patient treated with ipilimumab for recurrent metastatic melanoma. The patient presented with multiple falls that started after the third infusion of ipilimumab. Other symptoms were hoarseness of voice, motor deficits in his right arms, and tingling in both hands. The deficits progressed into near complete loss of movement and sensation in all four extremities over the course of two weeks. However, his bladder and bowel functions were intact. There was no history of fever, recent travel, exposure to sick contacts, insect bites, or gastrointestinal symptoms. Along with strong immune-mediated pharmacological response towards cancer cells, ipilimumab also induces immune-related adverse events (irAEs) within normal tissues by the mechanism of molecular mimicry.


Quality assessment of randomized controlled trials reporting on knee osteoarthritis treated with warming needle moxibustion.
To evaluate the quality of randomized controlled trials (RCTs) testing the efficacy of warming needle moxibustion on knee osteoarthritis (KOA). Nine databases were searched systematically including: the Cochrane Library (1/1993-10/2012), PubMed (1/1980-10/2012), EMBASE (1/1990-10/12012), SCI Expanded (1/1986-10/2012), Science Direct (1/1979-10/2012), Chinese Biomedical Literature Database disc (1/1978-10/2012), China National Knowledge Infrastructure Database (1/1979-10/2012), China Science and Technology Journal Database (a full text issue database of China, 1/1989-10/2012), and Wanfang Database (a full text issue database of China, 1/1990-10/12012). Traditional reference retrieval was also conducted. Language was limited to Chinese and English. We identified 37 RCTs that used warming needle moxibustion as an intervention and they were assessed with the Consolidated Standards for Reporting of Trials Statement 2010 (CONSORT 2010) and Standards for Reporting Interventions Controlled Trials of Acupuncture 2010 (STRICT A 2010). Of the 37 reports, only seventeen (45.95%) mentioned the random allocation of sequence methods, nine used unacceptable methods, and only one (2.70%) gave the description of the mechanism of allocation concealment. One study (2.70%) mentioned blinding, one (2.70%) had a sample size calculation, and twenty-three (62.16%) used reasonable statistical methods. Thirteen (35.14%) described the background and reason for the RCTs, three (8.11%) gave a description of lost or eliminated patients, and two (5.41%) reported accidental situations. Only three (8.11%) gave analysis of the RCT limitations. No report mentioned intentional analysis. The quality of the RCTs assessed in this study was from moderate to low. The design of RCTs, the methods of statistical analysis, and the description of reports information needs to be improved. CONSORT 2010 and STRICT A 2010 should be used to standardize the reporting of acupuncture RCTs in the future.


Cartilage-derived morphogenetic protein-1 and -2 are endogenously expressed in healthy and osteoarthritic human articular chondrocytes and stimulate matrix synthesis.
We investigated whether chondrocytes derived from osteoarthritic cartilage may lose their responsiveness to cartilage-derived morphogenetic protein-1, -2 (CDMP-1, -2) and osteogenic protein-1 (OP-1) compared with healthy cells, thus leading to an impaired maintenance of matrix integrity. Chondrocytes were isolated from articular cartilage from patients with and without osteoarthritic lesions. Cells were grown as monolayer cultures for 7 days in a chemically defined serum-free basal medium (BM) in the presence of recombinant CDMP-1, -2, and OP-1. Glycosaminoglycan synthesis was measured by [35S]Sulfate incorporation into newly synthesized macromolecules. Cell proliferation was investigated by [3H]Thymidine incorporation. The endogenous gene expression of CDMPs/OP-1 and their respective type I and type II receptors was examined using RT-PCR. The presence of CDMP proteins in tissue and cultured cells was detected by Western immunoblots. mRNAs coding for CDMPs and their respective receptors are endogenously expressed not only in healthy, but also in osteoarthritic cartilage. CDMP proteins are present in both normal and osteoarthritic articular cartilage and cultured chondrocytes. CDMP-1, CDMP-2 and OP-1 markedly increased glycosaminoglycan synthesis in both healthy (P< 0.01) and osteoarthritic (P< 0.05) human articular chondrocytes. A comparison of the glycosaminoglycan biosynthetic activity between healthy and osteoarthritic samples revealed no detectable difference, neither in stimulated nor in unstimulated cultures. [(3)H]Thymidine incorporation showed that CDMPs/OP-1 did not affect cell proliferation in vitro. CDMPs and OP-1 exert their anabolic effects on both healthy and osteoarthritic chondrocytes indicating no loss in responsiveness to these growth factors in OA. The endogenous expression of CDMPs/OP-1 and their receptors suggest an important role in cartilage homeostasis.


Mediastinal tumors in children: a single institution experience.
Mediastinal masses in children are a heterogeneous group of asymptomatic or potentially life-threatening congenital, infectious, or neoplastic lesions that present complex diagnostic and therapeutic dilemmas. Some patients are asymptomatic; in others, the mass may compress mediastinal structures and cause sudden asphyxia. In these cases, close cooperation is needed among pediatric surgeons, anesthesiologists, intensivists, oncologists, and radiologists. The files of 45 children with mediastinal masses admitted between 1986 and 1999 to the Pediatric Intensive Care Unit (PICU) of Schneider Children's Medical Center of Israel were reviewed. Twenty-one were admitted for perioperative care, and 21 for emergency care, including 19 with respiratory distress. Five of the emergency care group had asphyxia and 10 needed assisted ventilation. Two children were admitted for evaluation and 1 for leukopheresis. The children admitted on an emergency basis had more clinical findings than the postoperative group: almost 80% had dyspnea and more than 45% had oxygen desaturation; 33% had cough and noisy breathing, and 25%, superior vena cava syndrome or hepatosplenomegaly. Eight patients (17.8%) had benign disease and 37 (82.2%) malignant disease. The patients with a benign mass were significantly younger than the patients with a malignant mass (p<0.005); in 5 cases (12.5%), a congenital anomaly presented as a mediastinal mass. Most of the malignant masses were of hematologic origin (40.5%), followed by neurogenic tumors (27%). Twenty-seven patients underwent surgery, including 6 emergency procedures (3 partial resections, 2 biopsies, 1 lymph node biopsy). There were no intraoperative or postoperative deaths. The present series emphasizes the complex care children with a mediastinal mass require. They should be treated in a tertiary center with a multidisciplinary approach.


Continuous veno-venous hemofiltration improves hemodynamics in septic shock with acute renal failure without modifying TNFalpha and IL6 plasma concentrations.
Continuous hemofiltration improves hemodynamics in critically ill patients by removing cytokines from the plasma. The mechanism, however, remains to be clarified since recent studies show conflicting findings. The present study was therefore designed to evaluate hemodynamic changes and kinetics of tumor necrosis factor (TNF)alpha, interleukin (IL)1beta and IL6 in patients with septic shock and acute renal failure (ARF) undergoing continuous veno-venous hemofiltration (CWHF), over a 24-hour period. Eleven patients admitted to the ICU for septic shock with ARF were investigated with radial artery and pulmonary artery catheterization during isovolemic CWHF using AN69 hemofilters at a blood flow rate of 240 mL/min and ultrafiltration 1.65 +/- 0.33 L/h. Hemodynamic measurements (mean arterial pressure, right arterial pressure, pulmonary artery pressure, pulmonary vascular resistance, systemic vascular resistance, cardiac output and tissue oxygenation indeces) were obtained before and after 2h, 4h, 6h, 12h and 24 h of CVVHF. Blood samples from the pre- and postfilter lines and ultrafiltrate samples were collected for the radioimmunoassay of TNFalpha, IL1beta and IL6 before and at 2h, 4h, 6h, 12h and 24h. During CVVHF, mean arterial pressure rose from 67 +/- 7 mm Hg to 89 +/- 5 mm Hg (p < 0.05) and indexed systemic vascular resistance from 711 +/- 153 dyne.s.cm(-5)/m2 to 1,200 +/- 100 dyne.s.cm(-5)/m2 (p < 0.05). Serum lactate and oxygen consumption did not change. Mean arterial pressure and systemic vascular resistance were not correlated to the lowering of body temperature during CVVHF. Significant clearance of IL6 was achieved, but not of TNFa, though the plasma concentrations of both cytokines were unaffected throughout the study. IL1beta was not detectable. Two patients were discharged alive with normal renal function. In patients with septic shock and ARF, CVVHF improves mean arterial pressure and systemic vascular resistance. This effect does not appear to be related to the removal of cytokines. The effect of CVVHF on mortality and morbidity in the long term, in septic shock has still to be established.


Expression of the green fluorescent protein (GFP) in mycobacterium avium as a tool to study the interaction between Mycobacteria and host cells.
Mycobacterium avium is an intracellular pathogen able to invade and survive within macrophages and mucosal epithelial cells. The study of the interaction between M. avium and host cells is important to establish the mechanisms of pathogenesis of the infection. One of the limitations of microscopic study of intracellular M. avium is the difficulty of identifying isolated bacilli within cells. As a general strategy to visualize and analyse the influence of M. avium on intracellular trafficking, we cloned the gene encoding the green fluorescent protein (GFP) in M. avium. A vector was constructed by cloning the cDNA for the GFP of the bioluminescent jellyfish Aequorea victoria into an Escherichia coli/Mycobacteria shuttle vector (pMV261). The recombinant plasmid (pWES-4) was transformed into both E. coli and M. avium strain 104 (serovar 1). The transformants were screened for strong expression of the GFP. Transformed M. avium were clearly visible inside human macrophages and epithelial cells using fluorescence microscopy. These transformed M. avium should provide a useful tool for further study of intracellular behaviour.


Stature estimation from foramen magnum region in Chinese population.
Estimation of stature from body parts plays a vital role in identifying the dead. This study focused on dimensions of the foramen magnum region and examined the relationship between stature and the dimensions of the foramen magnum region in northern and southern Chinese populations. Measurements were taken on the skulls of 276 individuals (all male). Data on 48 individuals from northern China and 140 from southern China were used for further stature reconstruction of the above two populations in China. Statistical analyses indicate that bilateral variation is insignificant for all measurements except maximum length of condyle in the southern Chinese population (p < 0.01) and that the northern and southern populations differ significantly only in the minimum distance between condyles. Linear and multiple regression equations for stature estimation were established. The correlation coefficients between stature and the various measurements differed between the northern and southern Chinese populations.


[Causes of spread and return of scabies in health care institutes; literature analysis of 44 epidemics].
To determine the risk factors that contribute to the transmission and return of scabies in health care institutions. Literature analysis. Public Health Care Service Midden-Kennemerland. Heemskerk, the Netherlands. Search of Medline over the years 1976-1996 yielded 34 reports of 44 outbreaks. The contents were qualitatively examined on factors possibly contributing to the transmission and return of scabies in health care institutions. Six such factors that contribute to the transmission and return of scabies in health care institutions were found: (a) among residents in health care institutions a considerable number are, once infested, at risk of developing crusted scabies, (b) many people are exposed through close contact, (c) the generally long diagnostic delay, (d) insufficient survey of the epidemiological problem, (e) treatment failures and (f) incomplete post-intervention monitoring.


Craniofacial pain as the sole symptom of cardiac ischemia: a prospective multicenter study.
Craniofacial pain can be the only symptom of cardiac ischemia. Failure to recognize its cardiac source can put the patient's life at risk. The authors conducted a study to reveal the prevalence of, the distribution of and sex differences regarding craniofacial pain of cardiac origin. The authors prospectively selected consecutive patients (N = 186) who had had a verified cardiac ischemic episode. They studied the location and distribution of craniofacial and intraoral pain in detail. Craniofacial pain was the only complaint during the ischemic episode in 11 patients (6 percent), three of them who had acute myocardial infarction (AMI). Another 60 patients (32 percent) reported craniofacial pain concomitant with pain in other regions. The most common craniofacial pain locations were the throat, left mandible, right mandible, left temporomandibular joint/ear region and teeth. Craniofacial pain was pre-ponderantly manifested in female subjects (P = .031) and was the dominating symptom in both sexes in the absence of chest pain. Craniofacial pain commonly is induced by cardiac ischemia. This must be considered in differential diagnosis of toothache and orofacial pain. Because patients who have AMI without chest pain run a higher risk of experiencing a missed diagnosis and death, the dentist's awareness of this symptomatology can be crucial for early diagnosis and timely treatment.


[Primary urothelial carcinoma of the urethra. Apropos of a case].
We report an unusual case of primary transitional cell carcinoma in the bulbar urethra. The patient was a 52-year-old man with a history of sexually transmitted disease. The clinical presentation was bladder retention with urethral bleeding. Radiological examination and cystoscopy showed a bulbar urethral tumor. The pathological diagnosis was Grade III transitional cell carcinoma with invasion of the corpus spongiosum (T2). Partial resection of the urethra was performed and the patient has been without evidence of disease for two years.


Effect of long-term intensive endurance training on left ventricular structure and diastolic function in prepubertal children.
In children, the fact that cardiac anatomy and function, particularly during the diastolic phase, can adapt to endurance training is still uncertain. Therefore, this study was undertaken to evaluate the effect of a long-term intensive endurance swimming program on the cardiac structure and function of 10-11 year old children. The population consisted of 9 children who belonged to a local youth swimming team (S) and 11 recruited from a primary school to serve as a control group (C). The swimmers had been training on average 10 to 12 h x wk(-1) for at least 2 years. All the subjects were examined by M-mode, 2-dimensional and pulsed-wave Doppler analyses according to standard procedures recommended by the American Society of Echocardiography. Investigations were carried out at rest with the subjects in a supine position. The results showed that highly trained children exhibited significantly higher left ventricular (LV) internal diameter (S: 41.6+/-1.6, C: 39.0+/-2.2 mm/m(1/3) surface area, p<0.01) and LV mass (S: 68+/-7, C: 59+/-5 g/m2 SA, p<0.01). There were, however, no differences between S and C for chamber wall thickness (posterior wall S: 5.2+/-0.6, C: 5.3+/-0.6 mm/m(1/3) SA; septum S: 5.8+/-0.3, C: 5.8+/-0.4 mm/m(1/3) SA), LV systolic function parameters (ejection fraction S: 77.1+/-0.3, C: 77.7+/-0.4%; shortening fraction S: 38.9+/-3.0, C: 39.7+/-4.1%) and the diastolic function parameters, estimated from LV inflow velocitometry (E wave S: 1.04+/-0.12, C: 1.07+/-0.16 m/s; A wave S: 0.45+/-0.10, C: 0.55+/-0.11 m/s). Finally, transaortic Doppler examinations demonstrated similar resting cardiac output (Qc) between both groups (S: 3.76+/-0.81, C: 3.90+/-0.67 l x min(-1)). However, Qc were obtained with significantly lower heart rates (S: 69+/-7, C: 83+/-14 beat x min(-1), P<0.01) and higher stroke volumes (S: 55.2+/-8.0, C: 47.5+/-8.5 ml, P<0.05) in S when compared to C. Thus, these findings strongly suggest that, as has been shown before in adults, several cardiac adaptations (including resting bradycardia, increased stroke volume and enlarged left ventricular internal dimensions) can occur in prepubertal children as a result of intensive endurance training. However, our results did not demonstrate any effects of such training during prepuberty on both diastolic and systolic functions parameters.


Biophenols from agro-industrial wastes.
Large quantities of agro-based liquid wastes are produced every year and their disposal is often a problem for industries. In light of that, in this study prudent effort was done to screen the agro-industrial wastes - pineapple waste (PAW) and palm oil mill effluent (POME) for valuable biophenols product. Three different solvents; ethanol, acetone and distilled water were screened in order to enhance the process. All experiments were performed using fixed process conditions of solid to solvent ratio, temperatures, time and agitation speed. Effectiveness of extraction process to produce biophenol was based on high amount with more activity. POME was selected as potential source with biophenol content of 125.42 mg/L GAE.


Behavior shaping of complete denture patient: a theoretical approach.
The psychological status of a geriatric patient undergoing complete denture treatment is one of the key determinants of the success of prosthesis. Hence, the understanding and behavior management of such patients is of paramount importance for any clinician aspiring to be a successful in practice. Even though several attempts have been made to understand the effects of psychology of patients undergoing this particular treatment on the final outcome of treatment, no single theory or classification has been proposed so far as to be able to completely understand the thought process of geriatric patients. The aim of this paper is to propose a theoretical approach, a step by step guide to clinicians to better understand the thoughts, aspirations and expectations of complete denture patients and their effects and consequences in different patients, when not met with.


Changes in polysomal polyadenylated RNA and alpha-fetoprotein messenger RNA during hepatocarcinogenesis.
Polysomal polyadenylated RNA was isolated from preneoplastic and neoplastic livers obtained from rats kept on a choline-deficient diet containing ethionine for 8 and 25 to 32 weeks, respectively. Normal, preneoplastic, and neoplastic liver polysomal messenger RNA's (mRNA's) were hybridized with homologous and heterologous 3H-labeled complementary DNA's (cDNA's). The results show that, in terms of RNA mass, all or most of the polysomal polyadenylated RNA present in preneoplastic or neoplastic liver is also present in normal liver. This was induced by the similar extent of hybridization between [3H]cDNA transcribed from preneoplastic or neoplastic liver mRNA's with their homologous mRNA's and with mRNA from normal liver. Conversely, most or all of the polysomal polyadenylated RNA of normal liver is also found in preneoplastic and neoplastic livers, as indicated by the extent of hybridization of [3H]cDNA transcribed from normal liver with mRNA's from normal, preneoplastic, and neoplastic livers. Shifts in the relative abundance of mRNA sequences were detected in the polysomal mRNA of preneoplastic livers and especially in the mRNA of neoplastic liver. Hybridization of alpha-fetoprotein cDNA with liver polyadenylated RNA showed a substantial increase in alpha-fetoprotein mRNA content after 8 and 15 weeks of feeding the carcinogenic diet. Similar experiments using globin cDNA failed to show an increase in globin mRNA content in preneoplastic livers.


On the use of the experimentally determined enzyme inhibition constant as a measure of absolute binding affinity.
Defined as a state function representing an inhibitor's absolute affinity for its target enzyme, the experimentally determined enzyme inhibition constant (Ki) is widely used to rank order binding affinities of different inhibitors for a common enzyme or different enzymes for a common inhibitor and to benchmark computational approaches to predicting binding affinity. Herein, we report that adsorption of bis(7)-tacrine to the glass container surface increased its Ki against Electrophorus electricus acetylcholinesterase (eeAChE) to 3.2 ± 0.1 nM (n = 5) compared to 2.9 ± 0.4 pM (n = 5) that was determined using plastic containers with other assay conditions kept the same. We also report that, due to binding or "adsorption" of bis(7)-tacrine to the inactive eeAChE, the bis(7)-tacrine Ki increased from 2.9 ± 0.4 pM (n = 5) to 734 ± 70 pM (n = 5) as the specific eeAChE activity decreased from 342 U/mg to 26 U/mg while other assay conditions were kept the same. These results caution against using Kis to rank order binding potencies, define selectivity, or benchmark computational methods without knowing detailed assay conditions.


Multisegmental cervical ossification of the posterior longitudinal ligament: anterior vs posterior approach.
To determine the surgical approach in patients with multisegmental (four or more segments) OPLL of the cervical spine. Data of 27 patients who had undergone either an anterior (corpectomy with excision of OPLL and interbody fusion = 14 patients) or posterior approach (laminectomy = 12, laminoplasty = 1 patient) for the multisegmental cervical OPLL was analyzed retrospectively. The patients in each group were statistically similar in respect to preoperative factors such as age, duration of symptoms, preoperative modified Japanese orthopedic association score, OPLL thickness, effective canal diameter, and antero-posterior cord compression ratio. The clinical outcome was assessed by the Harsh grading system and recovery rate was assessed by Hirabayashi method. There was no statistical difference in the outcome, and recovery rate. Nine patients developed complications after anterior approach in contrast to one after posterior approach. In patients with multisegmental cervical OPLL, there was no significant difference in the short-term recovery rate and outcome between two groups. The immediate postoperative complications were less in patients who had undergone posterior approach. From our analysis, it appears that the posterior approach is probably the preferred method of treatment in a multisegmental OPLL in absence of preoperative kyphosis.


[Aseptic osteonecrosis in renal transplantation ; apropos of 29 cases].
Over a period of observation of 14 years, one or more aspetic osteonecroses (AON) were discovered in 29 patients who had undergone renal transplantation. Altogether 64 AON were discovered. In patients who had survived at least 1 year, the frequency of this lesion was 18 percent. These transplantation necroses were often bilateral (16 cases out of 21 AON of the femoral head) or multiple (6 patients presenting AON in more than 3 sites) ; necroses were sometimes found in unusual sites (shoulder, ankle, upper end of the tibia, scaphoid, condyle of the humerus). The AONs of the lower limbs were remarkable because of their extent and because of the rapid evolution of the radiological signs. This is in contrast to the moderate nature of the pain. Latent types of necrosis are also found (3 cases of AON of the femoral head). During a search for factors favouring the development of AON, the authors noted that the average duration of haemodialysis was longer in the patients with AON than in a control group of transplant patients. The average daily dose of corticoids for the first six months after transplantation was not significantly different in the two groups studied. However, the 15 patients with transplants who were not given corticoids did not develop AON.


A systemic evaluation of drug in acrylic pressure sensitive adhesive patch in vitro and in vivo: The roles of intermolecular interaction and adhesive mobility variation in drug controlled release.
Though acrylic pressure sensitive adhesives (PSAs) are widely used in transdermal drug delivery system, molecular details of drug-PSA interactions, PSA molecular mobility variations and their influences on drug skin permeation are unclear. In this study, three classes of acrylic PSAs containing hydroxyl (AAOH), carboxyl (AACOOH) and non-functional group (AAnone) were synthesized. Their abilities of controlling drug release were evaluated using propranolol (PRO) and zaltoprofen (ZAL) in vitro and in vivo. Interaction details were identified by FT-IR, solid-state NMR and molecular modeling. Thermodynamic activity of drug and strength of drug-PSA interaction were characterized using miscibility study. PSA mobility was characterized using thermal analysis and rheology study. Thus, ionic interaction reduced the thermodynamic activity of PRO and mobility of AACOOH, which made PRO-AACOOH obtain a significant lower bioavailability (11.8±0.7%) than these of PRO-AAnone (40.7±2.5%) and PRO-AAOH (42.3±2.9%). Though thermodynamic activity of ZAL in AACOOH was lower than that in AAOH due to the hydrogen bonding, bioavailability of ZAL-AAOH (19.0±4.1%) exhibited no significant difference with ZAL-AACOOH (15.4±2.8%), mainly because AAOH mobility was decreased by ZAL. In conclusion, the strength, types and involved functional groups of drug-PSA interactions were identified. On this basis, it was found that different control patterns of drug release were not only caused by the thermodynamic or kinetic hindrance effects of drug-PSA interactions, but also influenced by the interactions introduced PSA mobility variations, which was an innovative mechanism of controlled release in transdermal patch. The conclusions extended our understanding about the mechanism of controlled drug release of drug-in-adhesive patch. In addition, they contributed to the design of TDDS and custom acrylic PSAs.


Familial Retinoblastoma: Raised Awareness Improves Early Diagnosis and Outcome.
Purpose. To study the impact of awareness of retinoblastoma in the affected families on the management and outcome of familial retinoblastoma patients. Methods and Materials. This is a retrospective, clinical case series of 44 patients with familial retinoblastoma. Collected data included patient's demographics, laterality, family history, age at diagnosis, presenting signs, treatment modalities, tumor stage, eye salvage rate, metastasis, and mortality. Results. Out of 200 retinoblastoma patients in our registry, 44 (22%) patients were familial, 18 were probands, and 26 were second, third, or fourth affected family members. There were 76 affected eyes: 31 eyes of probands and 45 eyes of the other affected family members. Among probands, all patients (100%) had at least one eye enucleated: 58% (18 eyes) of the affected eyes were enucleated and 32% (10 eyes) of the affected eyes were radiated. On the other hand, among the nonprobands, only 20% had one eye enucleated, and only 4 eyes (9%) received radiation. The eye salvage rate was significantly higher in the nonprobands than in the probands in this series (p = 0.00206). Patients diagnosed by screening (38%) had excellent visual outcome, and both eyes were salvaged. Conclusion. Awareness of families of the possibility of retinoblastoma and adequate screening led to a significantly higher rate of eye salvage in patients with familial retinoblastoma.


Properties of alkaline phosphatase in crude homogenates of human diploid fibroblasts.
The kinetic properties of the "constitutive" and the "induced" alkaline phosphatase in diploid fibroblasts are compared with those of the enzymes in crude tissue homogenates. Both the constitutive as the induced enzyme have properties comparable with those of the liver-bone-kidney group. The induced alkaline phosphatase clearly differs from the "constitutive" alkaline phosphatase concerning the effect of high concentrations of L-phenylalanine and the effect of Mg2+ ions. The induced alkaline phosphatase seems to be identical with the enzyme in liver, but the constitutive alkaline phosphatase could not be identified.


Occupational prognosis factors for ulnar nerve entrapment at the elbow: A systematic review.
Although ulnar nerve entrapment is the second most common entrapment neuropathy, there is a dearth of studies identifying occupational prognosis factors. We carried out a systematic review of the occupational prognosis factors for ulnar nerve entrapment in order to identify professions at risks and allow better follow-up for their workers. Using the key words, "ulnar OR cubital", "neuropathy OR tunnel", and "work OR occupational" without limitations, original prospective studies were selected from four databases (PubMed, Embase, Web of Science, Cochrane Library) after two rounds (valid design, valid prognosis outcome reported, valid work exposure). Associations between prognosis for ulnar neuropathy and occupational factors were extracted and analyzed qualitatively. Dating from 1981 to 2013, three prospective studies were included; 1420 cases of ulnar nerve entrapment were followed for an average of 4 years and occupational exposure was retrieved. The only high-quality study (related to this question) found a significant relationship between occupational exposure and prognosis with an odds ratio for ulnar nerve entrapment of 1.78 (1.10-2.88). The two other studies were less focused on the occupational prognosis factors; one found that work activity requiring effort had worse prognosis after surgery, while the other found no significant relationship between occupational hand exposure and prognosis. Occupations requiring high effort may be associated with more severe ulnar neuropathies, but further studies (exposure as well as associated disorders) are mandatory for clinicians to provide work task information to their patients.


Multiple myeloma: imaging evaluation of skeletal disease.
This patient is a 56-year-old woman with a history of IGG κ multiple myeloma diagnosed 15 years prior to admission. She had widespread lytic bone lesions and pathological fractures, which remarkably had not been accompanied by significant pain, but were mostly refactory to chemotherapy.


1997 Joint Commission on Health Care Organizations home care standards: what's new?
Even though there are no new home care standards for 1997, there are some changes in the standards' interpretations and documentation expectations. Not all of the new interpretations are stricter interpretations. In fact, most of the new 1997 standards interpretations are more flexible. New interpretations for other problematic home care standards will be addressed in future columns.


Functional analysis of tunicamycin-inducible gene A polypeptide from Aspergillus niger.
Tunicamycin-inducible gene A polypeptide (TIGA) is a member of the protein disulfide isomerase (PDI) family and is suggested to facilitate the folding of nascent polypeptides. The functional properties of TIGA were investigated here. TIGA acted as an isomerase, catalyzing the refolding of denatured and reduced ribonuclease A. TIGA also exhibited chaperone activity in the refolding of denatured prochymosin but not in the refolding of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), indicating that it had substrate specificity with respect to chaperone activity. Detailed study with a series of thioredoxin-motif (trx-motif) mutants revealed that the 2 trx-motifs of TIGA were not equal in activity. The N-terminal trx-motif was more active than the C-terminal trx-motif, and the first cysteine in each trx-motif was necessary for isomerase activity.


High prevalence of active and occult hepatitis B virus infections in healthcare workers from two provinces of South Africa.
Hepatitis B (HB) is a vaccine-preventable liver disease caused by infection with the blood-borne hepatitis B virus (HBV). South African healthcare workers (HCWs) may be at high risk of occupational exposure to HBV infection, since previous studies have found suboptimal levels of protection against HBV in HCWs. A descriptive prevalence study based on self-administered questionnaires with data on demographics and HB vaccination status, and stored serum samples collected from 2009 to 2012, from 333 HCWs working or studying in Gauteng and Mpumalanga province hospitals or nursing colleges, was conducted. Samples were tested for HB surface antigen (HBsAg), antibodies to HBsAg (anti-HBs), antibodies to HB core antigen (anti-HBc), and HBV deoxyribonucleic acid (DNA). The majority of HCWs from whom the serum samples were drawn were black (91.4% [298/326]), female (82.6% [275/333]) and had received at least one dose of HB vaccine (70.9% [236/333]). The average age was 38.8years (range: 19-62). Of the HCWs, 23.2% (73/314) were susceptible (negative for all markers); 9.6% (30/314) were infected (HBsAg and/or DNA positive); 29.0% (91/314) were exposed (positive for either HBsAg, anti-HBc, or DNA); 18.8% (59/314) were immune due to natural infection (anti-HBs and anti-HBc positive only); while 47.8% (150/314) were immune due to vaccination (anti-HBs positive only). Furthermore, HBV DNA was detected in 8.6% (27/314) and occult HBV infection (OBI) (HBV DNA positive but HBsAg negative) was found in 6.7% (21/314) of samples. This study, which is the first to report OBI in South African HCWs, found high rates of active HBV infection and sub-optimal protection against HBV in HCWs. There is a need to strengthen vaccination programmes through a policy that ensures protection for all HCWs and their patients.


[Do we need pathogen-free livestock for food safety?].
The reduction of the entry of pathogens in the food chain is an important premise in improving the safety of food of animal origin. Since food animals are the main reservoir for pathogens, the prevalence of pathogens in livestock is of great importance. Unfortunately, classical measures to improve animal health can not exclude the presence of the main food-borne zoonotic agents (Salmonella, Campylobacter, Listeria monocytogenes, verotoxinogene Escherichia coli, Toxoplasma gondii) in "clinically healthy" animals. Absence of pathogens in livestock must be regarded as an unrealistic aim. To achieve an effective improval of product safety through logistical, hygienic or technological measures both farmers and food producers need valid data about the prevalence of pathogens in livestock, in each animal and in raw material of animal origin, respectively. Yet available data are insufficient. New European directives and regulations concerning monitoring and control of zoonosis demand the systematic control of presence of zoonotic agents in livestock and later steps of the food chain.


Organic substances interfere with reverse transcription-quantitative PCR-based virus detection in water samples.
Reverse transcription (RT)-PCR-based virus detection from water samples is occasionally hampered by organic substances that are co-concentrated during virus concentration procedures. To characterize these organic substances, samples containing commercially available humic acid, which is known to inhibit RT-PCR, and river water samples were subjected to adsorption-elution-based virus concentration using an electronegative membrane. In this study, the samples before, during, and after the concentration were analyzed in terms of organic properties and virus detection efficiencies. Two out of the three humic acid solutions resulted in RT-quantitative PCR (qPCR) inhibition that caused >3-log10-unit underestimation of spiked poliovirus. Over 60% of the organics contained in the two solutions were recovered in the concentrate, while over 60% of the organics in the uninhibited solution were lost during the concentration process. River water concentrates also caused inhibition of RT-qPCR. Organic concentrations in the river water samples increased by 2.3 to 3.9 times after the virus concentration procedure. The inhibitory samples contained organic fractions in the 10- to 100-kDa size range, which are suspected to be RT-PCR inhibitors. According to excitation-emission matrices, humic acid-like and protein-like fractions were also recovered from river water concentrates, but these fractions did not seem to affect virus detection. Our findings reveal that detailed organic analyses are effective in characterizing inhibitory substances.


Antifungal activity of lichen compounds against dermatophytes: a review.
The growth rate inhibition of dermatophytes by compounds extracted by acetone, ethanol, methanol and water derived from representatives of several lichen genera (e.g. Caloplaca, Everniastrum, Heterodermia, Hypotrachyna, Platismatia and Ramalina) were compared on the basis of a worldwide review of published research. The examined dermatophytes included Epidermophyton floccosum, Microsporum audouinii, M. canis, M. gypseum, M. nanum, Trichophyton longifusus, T. mentagrophytes, T. rubrum, T. tonsurans and T. violaceum. The influence of selected secondary lichen compounds, for example, usnic acid, on the growth rates of these dermatophytes was also reviewed. The measurement of inhibition by lichen compounds was performed by several methods, but mostly those employing disc diffusion, broth dilution and agar dilution. The fungicidal activity of water-extracted compounds from Heterodermia leucomela and Hypotrachyna cirrhata and of methanol-extracted compounds from Evernia divaricata and Ramalina pollinaria, as well as protolichesterinic and 2-hydroxy-4-methoxy-3,6-dimethylbenzoic acids, are distinguished.


Selection of autologous CD4+ T-cells for adoptive T-cell substitution in patients with CD23+ B-cell CLL.
B-cell CLL (B-CLL) is accompanied by a progressive decrease in cellular immune functions, and treatment-related immunosuppression can further aggravate T-cell immunodeficiency. To reduce the risks of T-cell depletion, it seems feasible to collect autologous CD4+ cells at an early disease stage and subsequently reinfuse them during periods of profound T-cell depletion. We describe a two-step cell-selection method to obtain highly enriched CD4+ T-cells from leukapheresis compounds of patients with CD23+ B-CLL. The double selection procedure was performed using the CellPro Ceperate device, and consisted of CD4+ selection followed by CD23 purging to further remove contaminating CD23+ B-cells from the CD4+ cell fraction. The results of eight runs performed with leukapheresis material obtained from eight patients with CD23+ B-CLL at different disease stages are presented. The CD4/CD23 double cell-selection procedure resulted in the purification of > 90% CD4+ cells. Median recovery of CD4+ T lymphocytes after selection was 46%, and was negatively affected by the initial tumor cell load. The final T-cell fraction still contained lymphocytes of the B-CLL clone, as determined by FACS and PCR. The cell-processing procedure had no impact on T-cell function, as assessed by the in vitro production of the cytokine interferon-gamma. Moreover, the selected CD4+ cells retained their capacity to co-stimulate mitogen-induced B-cell IgG production in vitro. The described CD4 selection/CD23 depletion strategy is a suitable approach to obtaining high numbers of functional active autologous CD4+ T cells for adoptive T-cell transfer in patients with CD23+ BCLL.


Cementoblastoma arising in the maxilla of an 8-year-old boy: a case report.
Cementoblastoma is an uncommon disease, representing only 1-8% of all odontogenic tumours. Furthermore, this tumour is especially uncommon in children, as only five cases have been reported in this age group. Here, we describe a case of cementoblastoma arising in the maxilla of an 8-year-old boy, that was treated with a partial maxillectomy. The patient's facial appearance has remained satisfactory, and the tumour has not recurred in the 9 years after the operation.


Potential Societal and Cultural Implications of Transgenerational Epigenetic Methylation of Trauma and PTSD: Pathology or Resilience?
Psychological trauma is unique in that it is an environmental event that could induce biological changes and post-traumatic stress disorder (PTSD), depression, or other mood disorders in some patients. On the other hand, there may be no psychopathology (in most cases), or even sometimes post-traumatic growth and resilience. According to the DSM-5, trauma is a prerequisite for PTSD and traumatic stress disorder, but not for depressive episodes or mood disorders, or other psychiatric conditions. This paper brings attention to the preliminary literature on transgenerational inheritance due to trauma exposure and its societal and cultural implications. There is accumulating evidence that exposure to trauma can be passed transgenerationally through epigenetic inheritance leading to changes in gene expression and possible disorders or resilience. The effects of resilience from transgenerational inheritance have not been studied, but should be, for a full understanding not only of the disease risk across generations, but also of its social and cultural implications. The epigenetic pathologic effects across generations also need further studies, as the current research is preliminary; larger replications are needed for definitive and more complete understanding. I present here a glimpse of where we are, a vision of where we should go in terms of future research direction for disease risk transmission, and recommend studies of resilience and post-traumatic growth across generations, as well as other studies related to the societal implications at the population level.


Selection of Wild Lactic Acid Bacteria Strains as Promoters of Postbiotics in Gluten-Free Sourdoughs.
The occurrence of inflammatory responses in humans is frequently associated with food intolerances and is likely to give rise to irritable bowel disease. The use of conventional or unconventional flours to produce gluten-free baking doughs brings important technological and nutritional challenges, and the use of the sourdough biotechnology has the potential to overcome such limitations. In addition, the typical metabolic transformations carried out by Lactic Acid Bacteria (LAB) can become an important biotechnological process for the nutritional fortification and functionalization of sourdoughs due to the resulting postbiotics. In such a context, this research work aimed at isolating and selecting new LAB strains that resort to a wide range of natural environments and food matrices to be ultimately employed as starter cultures in gluten-free sourdough fermentations. Nineteen LAB strains belonging to the genera of Lactobacillus, Leuconostoc, Pediococcus, and Streptococcus were isolated, and the selection criteria encompassed their acidification capacity in fermentations carried out on chickpea, quinoa, and buckwheat flour extracts; the capacity to produce exopolysaccharides (EPS); and the antimicrobial activity against food spoilage molds and bacteria. Moreover, the stability of the LAB metabolites after the fermentation of the gluten-free flour extracts submitted to thermal and acidic treatments was also assessed.


Explaining the sawtooth: latitudinal periodicity in a circadian gene correlates with shifts in generation number.
Many temperate insects take advantage of longer growing seasons at lower latitudes by increasing their generation number or voltinism. In some insects, development time abruptly decreases when additional generations are fit into the season. Consequently, latitudinal 'sawtooth' clines associated with shifts in voltinism are seen for phenotypes correlated with development time, like body size. However, latitudinal variation in voltinism has not been linked to genetic variation at specific loci. Here, we show a pattern in allele frequency among voltinism ecotypes of the European corn borer moth (Ostrinia nubilalis) that is reminiscent of a sawtooth cline. We characterized 145 autosomal and sex-linked SNPs and found that period, a circadian gene that is genetically linked to a major QTL determining variation in post-diapause development time, shows cyclical variation between voltinism ecotypes. Allele frequencies at an unlinked circadian clock gene cryptochrome1 were correlated with period. These results suggest that selection on development time to 'fit' complete life cycles into a latitudinally varying growing season produces oscillations in alleles associated with voltinism, primarily through changes at loci underlying the duration of transitions between diapause and other life history phases. Correlations among clock loci suggest possible coupling between the circadian clock and the circannual rhythms for synchronizing seasonal life history. We anticipate that latitudinal oscillations in allele frequency will represent signatures of adaptation to seasonal environments in other insects and may be critical to understanding the ecological and evolutionary consequences of variable environments, including response to global climate change.


Antioxidant and Skin Anti-Aging Effects of Marigold Methanol Extract.
The objective of this study was to evaluate the antioxidant and anti-aging effects of marigold methanol extract (MGME) in human dermal fibroblasts. Total polyphenolic and flavonoid contents in MGME were 74.8 mg TAE (tannic acid equivalent)/g and 85.6 mg RE (rutin equivalent)/g, respectively. MGME (500 μg/mL) increased 1,1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2'-azino-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical-scavenging, and superoxide dismutase (SOD)-like antioxidant activities by 36.5, 54.7, and 14.8%, respectively, compared with the control. At 1,000 μg/mL, these activities increased by 63.7, 70.6, and 20.6%, respectively. MGME (100 μg/mL) significantly increased the synthesis of type 1 procollagen by 83.7% compared with control treatment. It also significantly decreased Matrix Metalloproteinase-2 (MMP-2) activity and MMP-1 mRNA expression by 36.5% and 69.5%, respectively; however, it significantly increased laminin-5 mRNA expression by 181.2%. These findings suggest that MGME could protect human skin against photo-aging by attenuating oxidative damage, suppressing MMP expression and/or activity as well as by stimulating collagen synthesis.


Leukocyte and fibroblast interferon genes are located on human chromosome 9.
At least eight leukocyte interferon genes (IFL) and the single fibroblast interferon gene (IFF) have been located on chromosome 9 in humans. In somatic cell hybrids of human and mouse cells containing a normal complement of mouse parental cell chromosomes but reduced numbers of human chromosomes, the human leukocyte and fibroblast interferon DNA sequences were present only when human chromosome 9 was also present.


Nuclear transfer of adult bone marrow mesenchymal stem cells: developmental totipotency of tissue-specific stem cells from an adult mammal.
Recent studies have demonstrated that somatic stem cells have a flexible potential greater than previously expected when they are transplanted into different tissues. On the other hand, recent studies also have revealed that these potentials might occur because of spontaneous cell fusion with recipient cells. The nuclei of somatic cells could have been reprogrammed when they were artificially or spontaneously fused with mouse embryonic stem (ES) cells. The resultant hybrid cells acquired a developmental pluripotency that the original somatic cells did not have but that ES cells did. LaBarge and Blau (Cell 2002; 111:589-601) demonstrated that adult bone marrow-derived cells contributed to muscle tissue in a stepwise biological progression. This means that bone marrow-derived cells became satellite cells of mononucleate muscle stem cells after the first irradiation-induced damage to the mouse, and after the second irradiation-induced damage, multinucleate myofibers appeared from the bone marrow-derived cells. Considered together, the differentiation potential of the somatic stem cell nucleus itself remains unclear. Although the pluripotency of somatic stem cell populations has been evaluated, the developmental totipotency of the nuclei of somatic stem cells, whether or not they fused with other cells, has not been shown, except in only one study concerning fetal neural cells (never in adult stem cells). Here, we showed the developmental totipotency of adult bovine mesenchymal stem cells by nuclear transfer.


Variation in below-ground carbon fluxes along a Populus hybridization gradient.
Here, soil CO(2) efflux, minirhizotron fine root production (FRP), and estimated total below-ground carbon allocation (TBCA) were examined along an elevation and hybridization gradient between two cottonwood species. FRP was 72% greater under high-elevation Populus angustifolia, but soil CO(2) efflux and TBCA were 62% and 94% greater, respectively, under low-elevation stands dominated by Populus fremontii, with a hybrid stand showing intermediate values. Differences between the responses of FRP, soil CO(2) efflux and TBCA may potentially be explained in terms of genetic controls; while plant species and hybridization explained variance in carbon flux, we found only weak correlations of FRP and TBCA with soil moisture, and no correlations with soil temperature or nitrogen availability. Soil CO(2) efflux and TBCA were uncorrelated with FRP, suggesting that, although below-ground carbon fluxes may change along environmental and genetic gradients, major components of below-ground carbon flux may be decoupled.


The behavioral effects of lesions of the hippocampus: a review.
Many investigations have been conducted in an effort to deduce the nature of hippocampal function. This paper is an overview of the work done by several researchers in their attempt to find the possible connections between overt behaviors and hippocampal structures in the rat.


DNA microarray technology used for studying foodborne pathogens and microbial habitats: minireview.
Microarray analysis is an emerging technology that has the potential to become a leading trend in bacterial identification in food and feed improvement. The technology uses fluorescent-labeled probes amplified from bacterial samples that are then hybridized to thousands of DNA sequences immobilized on chemically modified glass slides. The whole gene or open reading frame(s) is represented by a polymerase chain reaction fragment of double-strand DNA, approximately 1000 base pair (bp) or 20-70 bp single-strand oligonucleotides. The technology can be used to identity bacteria and to study gene expression in complex microbial populations, such as those found in food and gastrointestinal tracts. Data generated by microarray analysis can be potentially used to improve the safety of our food supply as well as ensure the efficiency of animal feed conversion to human food, e.g., in meat and milk production by ruminants. This minireview addresses the use of microarray technology in bacterial identification and gene expression in different microbial systems and in habitats containing mixed populations of bacteria.


Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on Alzheimer's Disease (AD): Detection of Lipopolysaccharide (LPS) in AD Hippocampus.
Although the potential contribution of the human gastrointestinal (GI) tract microbiome to human health, aging, and disease is becoming increasingly acknowledged, the molecular mechanics and signaling pathways of just how this is accomplished is not well-understood. Major bacterial species of the GI tract, such as the abundant Gram-negative bacilli Bacteroides fragilis (B. fragilis) and Escherichia coli (E. coli), secrete a remarkably complex array of pro-inflammatory neurotoxins which, when released from the confines of the healthy GI tract, are pathogenic and highly detrimental to the homeostatic function of neurons in the central nervous system (CNS). For the first time here we report the presence of bacterial lipopolysaccharide (LPS) in brain lysates from the hippocampus and superior temporal lobe neocortex of Alzheimer's disease (AD) brains. Mean LPS levels varied from two-fold increases in the neocortex to three-fold increases in the hippocampus, AD over age-matched controls, however some samples from advanced AD hippocampal cases exhibited up to a 26-fold increase in LPS over age-matched controls. This "Perspectives" paper will further highlight some very recent research on GI tract microbiome signaling to the human CNS, and will update current findings that implicate GI tract microbiome-derived LPS as an important internal contributor to inflammatory degeneration in the CNS.


Technology-Based Interventions for Asthma-Can They Help Decrease Health Disparities?
Asthma is a condition that has consistently demonstrated significant health outcome inequalities for minority populations. One approach used for care of patients with asthma is the incorporation of technology for behavioral modification, symptom monitoring, education, and/or treatment decision making. Whether such technological interventions can improve the care of black and inner-city patients is unknown. We reviewed all randomized controlled trial technological interventions from 2000 to 2015 performed in minority populations. A total of 16 articles met inclusion and exclusion criteria; all but 1 was performed in a childhood or adolescent age group. The interventions used MPEG audio layer-3 players, text messaging, computer/Web-based systems, video games, and interactive voice response. Many used tailored content and/or a specific behavior theory. Although the interventions were based on technology, most required additional special staffing. Subject user satisfaction was positive, and improvements were noted in asthma knowledge, medication adherence, asthma symptoms, and quality of life. Unfortunately, health care utilization (emergency department visits and/or hospitalizations) was typically not improved by the interventions. Although no single intervention modality was vastly superior, the computer-based interventions appeared to have the most positive results. In summary, technology-based interventions have a high level of user satisfaction among minority and urban/low-income individuals with asthma, and can improve asthma outcomes. Further large-scale studies are needed to assess whether such interventions can decrease health disparities in asthma.


Effects of penicillin-binding protein 4 overproduction in Staphylococcus aureus.
The pbp4 gene of a Staphylococcus aureus strain selected stepwise in vitro for growth on increasing concentrations of penicillin and of its susceptible parent strain showed overall identity except in the promoter region. In the mutant a deletion upstream of the pbp4 structural gene removed 90 nucleotides (nt) that were framed by a 12 nt inverted repeat. This deletion occurred in step 4 of the in vitro selection procedure and was paralleled by a significant increase in the penicillin-binding protein 4 (PBP4) production. The in vitro step selected mutant showed a remarkable increase in the cross-linking of the peptidoglycan compared to its parent. This was linked to morphological changes in the appearance of the cells, which were surrounded by a very thick and fuzzy cell wall.


A prospective study of offspring of women with psychosis: visual dysfunction in early childhood predicts schizophrenia-spectrum disorders in adulthood.
Children with visual dysfunction have perinatal, neurological, visual-perceptual and cognitive abnormalities, similar to schizophrenia patients. We prospectively investigated whether visual dysfunction in childhood selectively predicts adult schizophrenia-spectrum disorders, and is related to childhood neurological abnormality. Offspring of mothers with and without a history of psychosis were prospectively assessed with vision tests at 4 years, neurological examinations at 6 years, and interviews for psychiatric disorders at follow-up (93% effective, n=166) at 22 years. In the total sample and high-risk (HR) offspring, visual dysfunction at 4 years, and its severity, were associated only with schizophrenia-spectrum disorders in adulthood, and with neurological abnormality at 6 years. Visual dysfunction at 4 years of age selectively predicts schizophrenia-spectrum disorders in adulthood among HR offspring, this likely reflecting disturbed neurological development.


Targeting pro-invasive oncogenes with short chain fatty acid-hexosamine analogues inhibits the mobility of metastatic MDA-MB-231 breast cancer cells.
Per-butanoylated N-acetyl-D-mannosamine (Bu(4)ManNAc), a SCFA-hexosamine cancer drug candidate with activity manifest through intact n-butyrate-carbohydrate linkages, reduced the invasion of metastatic MDA-MB-231 breast cancer cells unlike per-butanoylated-D-mannose (Bu(5)Man), a clinically tested compound that did not alter cell mobility. To gain molecular-level insight, therapeutic targets implicated in metastasis were investigated. The active compound Bu(4)ManNAc reduced both MUC1 expression and MMP-9 activity (via down-regulation of CXCR4 transcription), whereas "inactive" Bu(5)Man had counterbalancing effects on these oncogenes. This divergent impact on transcription was linked to interplay between HDACi activity (held by both Bu(4)ManNAc and Bu(5)Man) and NF-kappaB activity, which was selectively down-regulated by Bu(4)ManNAc. Overall, these results establish a new therapeutic end point (control of invasion) for SCFA-hexosamine hybrid molecules, define relative contributions of molecular players involved in cell mobility and demonstrate that Bu(4)ManNAc breaks the confounding link between beneficial HDACi activity and the simultaneous deleterious activation of NF-kappaB often found in epigenetic drug candidates.


Effect of Number of Bombus impatiens (Hymenoptera: Apidae) Visits on Eggplant Yield.
Eggplant (Solanum melongena L.) is a crop with perfect flowers capable of self-pollination. Insect pollination enhances fruit set, but little is known about how pollination success varies by number of visits from bumble bees. To quantify the efficiency of bumble bees at pollinating eggplants, we allowed 1, 2, 6, and 12 bumble bees (Bombus impatiens Cresson) to visit eggplant flowers and compared percentage of flowers that set fruit, fruit weight, and seed set after 3 wk. We compared yield from these visit numbers to eggplant flowers that were left open for unlimited visitation. Eggplant flowers set the most fruit from open-pollination and 12 visits. Larger, seedier fruits were formed in open-pollinated flowers. However, fruit characteristics in the 12 visit treatment were similar to lower visitation frequencies. We confirm B. impatiens as an efficient eggplant pollinator and document the greatest benefit from 12 bumble bee visits and open-pollinated flowers. To maintain effective eggplant pollination, local conditions must be conducive for bumble bee colony establishment and repeated pollen foraging trips.


Design and synthesis of enantiomers of 3,5-dinitro-o-tyrosine: alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropanoic acid (AMPA) receptor antagonists.
The R- and S-isomers of 3,5-dinitro-o-tyrosine (6a,b) have been synthesized through the use of chemoenzymatic synthesis and shown to bind differentially with the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropanoic acid (AMPA, 3) receptors. The phenolic functional group of these o-tyrosine analogues was designed to act as a bioisostere of the gamma-carboxyl group of glutamate. The S-isomer of 3,5-dinitro-o-tyrosine (6b) was 6.5 times more potent than the R-isomer (6a) in inhibiting [3H]AMPA binding with IC50 values of 13 +/- 7 and 84 +/- 26 microM, respectively. The phenolic group was important for binding affinity since the methoxy compound 7 was less potent than the phenolic compound 6 in inhibiting the binding of AMPA. The free amino group was also shown to be important since the N-acetyl analogue 15 and the N-t-BOC compounds 16 and 17 exhibited very low affinity for the AMPA receptors. AMPA receptor functional tests showed that the o-tyrosine analogues are antagonists and that the S-isomer 6b (IC50 = 630 +/- 140 microM) was more potent than the racemate 6 (IC50 = 730 +/- 88 microM) while the R-isomer 6a was inactive up to 1 mM concentration, which is consistent with the S-isomer having higher binding affinity than the R-isomer.


Time Trends of Aspirin and Warfarin Use on Stroke and Bleeding Events in Chinese Patients With New-Onset Atrial Fibrillation.
Much of the clinical epidemiology and treatment patterns for patients with atrial fibrillation (AF) are derived from Western populations. Limited data are available on antithrombotic therapy use over time and its impact on the stroke or bleeding events in newly diagnosed Chinese patients with AF. The present study investigates time trends in warfarin and aspirin use in China in relation to stroke and bleeding events in a Chinese population. We used a medical insurance database involving > 10 million individuals for the years 2001 to 2012 in Yunnan, a southwestern province of China, and performed time-trend analysis on those with newly diagnosed AF. Cox proportional hazards time-varying exposures were used to determine the risk of stroke or bleeding events associated with antithrombotic therapy among patients with AF. Among the randomly sampled 471,446 participants, there were 1,237 patients with AF, including 921 newly diagnosed with AF, thus providing 4,859 person-years of experience (62% men; mean attained age, 70 years). The overall rate of antithrombotic therapy was 37.7% (347 of 921 patients), with 4.1% (38 of 921) on warfarin and 32.3% (298 of 921) on aspirin. Antithrombotic therapy was not related to stroke/bleeding risk scores (CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke (doubled)] score, P = .522; CHA2DS2-VASc [congestive heart failure, hypertension, age ≥ 75 years (doubled), diabetes mellitus, stroke or transient ischemic attack (doubled), vascular disease, age 65 to 74 years, and female sex] score, P = .957; HAS-BLED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 years), drugs/alcohol concomitantly] score, P = .095). The use of antithrombotic drugs (mainly aspirin) increased in both women and men over time, with the rate of aspirin increasing from 4.0% in 2007 to 46.1% in 2012 in the former, and from 7.7% in 2007 to 61.9% in 2012 in the latter (P for trend for both, < .005). In the overall cohort, the annual stroke rate was approximately 6% and the annual major bleeding rate was about 1%. Compared with nonantithrombotic therapy, the hazard ratio for ischemic stroke was 0.68 (95% CI, 0.39-1.18) for aspirin and 1.39 (0.54-3.59) for warfarin. Aspirin use increased among Chinese patients newly diagnosed with AF, with no relationship to the patient's stroke or bleeding risk. Warfarin use was very low. Given the health-care burden of AF and its complications, our study has major implications for health-care systems in non-Western countries, given the global burden of this common arrhythmia.


Maternal-fetal status of copper, iron, molybdenum, selenium, and zinc in obese pregnant women in late gestation.
Obesity is well known to be a contributory risk factor for several disease states, including diabetes mellitus. Further, obese women are more prone to have babies born with congenital abnormalities. Paucity of data on maternal-fetal disposition of essential trace elements in obese pregnancies prompted us to undertake this study. Maternal venous and umbilical arterial and venous samples were collected from obese patients (body mass index >30) and control pregnant women (body mass index <25) at time of spontaneous delivery or cesarean sections and concentrations of essential trace elements such as Cu, Fe, Mo, Se, and Zn determined in various samples by atomic absorption spectrophotometry. Activities of antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and total antioxidant activity in maternal and umbilical blood were assessed using appropriate reagent kits. Maternal-fetal disposition and exchange parameters of elements studied were assessed using established criteria. Concentrations of Cu, Fe, Mo, Se, and Zn in the serum of control pregnant women at time of delivery averaged 2232.6, 2398.1, 10.9, 108.9, and 661.9 microg/L respectively, whereas in the obese group, the values of the above elements averaged 2150.3, 2446.8, 12.6, 96.8, and 838.9 microg/L respectively. Umbilical vein/maternal vein ratios of Cu, Fe, Mo, Se, and Zn in the control group averaged 0.29, 1.93, 1.06, 0.76, and 1.12, respectively, whereas in the obese group, their fetal-maternal ratios averaged 0.32, 2.23, 1.06, 0.78, and 1.53, respectively. The Cu : Zn ratio in the maternal vein of the obese group (3.60 +/- 0.20) was significantly lower (Student's t-test; p < 0.05) than that of the controls (2.50 +/- 0.19); however, Cu : Fe ratio (1.04 +/- 0.08 vs 1.02 +/- 0.09) was not significantly different (Student's t-test; p > 0.05) in the two groups. Varying differences were noted in the case of antioxidant enzyme activities between the control and study groups. We conclude that obesity is associated with alterations in maternal-fetal disposition of some essential trace elements and antioxidant enzyme status and that these alterations could pose a potential health risk for the mother as well as the fetus.


Generating viable mice with heritable embryonically lethal mutations using the CRISPR-Cas9 system in two-cell embryos.
A substantial number of mouse genes, about 25%, are embryonically lethal when knocked out. Using current genetic tools, such as the CRISPR-Cas9 system, it is difficult-or even impossible-to produce viable mice with heritable embryonically lethal mutations. Here, we establish a one-step method for microinjection of CRISPR reagents into one blastomere of two-cell embryos to generate viable chimeric founder mice with a heritable embryonically lethal mutation, of either Virma or Dpm1. By examining founder mice, we identify a phenotype and role of Virma in regulating kidney metabolism in adult mice. Additionally, we generate knockout mice with a heritable postnatally lethal mutation, of either Slc17a5 or Ctla-4, and study its function in vivo. This one-step method provides a convenient system that rapidly generates knockout mice possessing lethal phenotypes. This allows relatively easy in vivo study of the associated genes' functions.


Improvement of shotgun proteomics in the negative mode by carbamylation of peptides and ultraviolet photodissociation mass spectrometry.
Although acidic peptides compose a substantial portion of many proteomes, their less efficient ionization during positive polarity electrospray ionization (ESI) impedes their detection in bottom-up mass spectrometry workflows. We have implemented a derivatization strategy based on carbamylation which converts basic amine sites (Lys, N-termini) to less basic amides for enhanced analysis in the negative mode. Ultraviolet photodissociation (UVPD) is used to analyze the resulting peptide anions, as demonstrated for tryptic peptides from bovine serum albumin and Halobacterium salinarum in a high throughput liquid chromatography/tandem mass spectrometry (LC/MS/MS) mode. LC/UVPD-MS of a carbamylated H. salinarum digest resulted in 45% more identified peptides and 25% more proteins compared to the unmodified digest analyzed in the negative mode.


[Home hospice care, working support and rehabilitation for MS/NMO].
There are a huge amount of physical, mental and financial handicaps to patients with multiple sclerosis (MS) or neuromyelitis optica (NMO) and their family members, although treatment strategies have remarkably progressed recently. Among many important issues, to support them, here we make issues of home hospice care, working support and rehabilitation. We should consider social immaturity and ignorance to resolve the issues, and the key point to contribute useful support is consistent cooperation among medical teams and appropriate understanding of MS/NMO by all the people in our society as well as medical staffs.


[The design of the ultrasonic Doppler spectrum analyze system for the naval blood stream of fetus].
The design of the Ultrasonic Doppler Specturm Analyze System for the naval blood stream of the fetus is discussed, mainly on the sampling method of the Doppler signals and the algorithm of the blood stream parameters. Because the DSP chip is not used in the AD cardboard, the hardware design is not only simplified, but also works more steady. In the process of the blood stream parameters, an autochange method of the amplitude threshold and a time-out control technology are used, so the algorithm has good adaptation and works very stable.


Trends in fentanyl prescriptions and fentanyl-related mortality in Australia.
The study aims to quantify trends in fentanyl prescribing and fentanyl mortality in Australia within the context of concern among health professionals concerning increasing accessibility of fentanyl, and the harms that may arise as a result. This paper presents data on prescribing patterns of fentanyl by 10 year age group adjusted by population rate, detailed analyses of fentanyl-related deaths from the National Coronial Information System and deaths adjusted for prescribing levels within Australia. Fentany prescriptions have increased and are most prevalent among Australians aged over 80 years. One hundred and thirty-six fentanyl-related deaths were recorded during 2000-2011; 54% of decedents had a history of injecting drug use and, among this group, 95% had injected fentanyl at the time of death; 62% of deaths recorded misuse (most notably injection) of fentanyl; 50% recorded a history of drug dependence and 40% a mental health problem; 37% recorded a history of chronic pain; and 36% recorded fentanyl as being prescribed at the time of death. Deaths were primarily among Australians under 47 years of age. There have been significant increases in fentanyl prescribing in Australia. It is unclear what proportion of this increase represents legitimate treatment of pain. Fentanyl deaths have also increased, although mortality is currently low in Australia. A large proportion of the deaths involved the injection of diverted fentanyl, highlighting the need for messages regarding safer injecting practices targeting people who inject drugs, and strategies to minimise the risks of diversion.


The Diarylprolinol Silyl Ethers: Ten Years After.
Asymmetric organocatalysis has experienced an incredible development since the beginning of this century. The expansion of the field has led to a large number of efficient types of catalysts. One group, the diarylprolinol silyl ethers, was introduced in 2005 and has been established as one of the most frequently used in aminocatalysis. In this Minireview, we will take a look in the rear-view mirror, ten years after the introduction of the diarylprolinol silyl ethers. We will focus on the perspectives of the different activation modes made available by this catalytic system. Starting with a short introduction to aminocatalysis, we will outline the properties that have made the diarylprolinol silyl ethers a common choice of catalyst. Furthermore, we will describe the major tendencies in the activation and reaction concepts developed with regard to reactivity patterns and combinations with other activation concepts.


Comparison between B·R·A·H·M·S PCT direct, a new sensitive point-of-care testing device for rapid quantification of procalcitonin in emergency department patients and established reference methods - a prospective multinational trial.
Procalcitonin (PCT) is increasingly being used for the diagnostic and prognostic work up of patients with suspected infections in the emergency department (ED). Recently, B·R·A·H·M·S PCT direct, the first high sensitive point-of-care test (POCT), has been developed for fast PCT measurement on capillary or venous blood samples. This is a prospective, international comparison study conducted in three European EDs. Consecutive patients with suspicion of bacterial infection were included. Duplicate determination of PCT was performed in capillary (fingertip) and venous whole blood (EDTA), and compared to the reference method. The diagnostic accuracy was evaluated by correlation and concordance analyses. Three hundred and three patients were included over a 6-month period (60.4% male, median age 65.2 years). The correlation between capillary or venous whole blood and the reference method was excellent: r2=0.96 and 0.97, sensitivity 88.1% and 93.0%, specificity 96.5% and 96.8%, concordance 93% and 95%, respectively at a 0.25 μg/L threshold. No significant bias was observed (-0.04 and -0.02 for capillary and venous whole blood) although there were 6.8% and 5.1% outliers, respectively. B·R·A·H·M·S PCT direct had a shorter time to result as compared to the reference method (25 vs. 144 min, difference 119 min, 95% CI 110-134 min, p<0.0001). This study found a high diagnostic accuracy and a faster time to result of B·R·A·H·M·S PCT direct in the ED setting, allowing shortening time to therapy and a more wide-spread use of PCT.


Knowledge and attitude of healthcare workers about Middle East Respiratory Syndrome in multispecialty hospitals of Qassim, Saudi Arabia.
With the increase in prevalence of Middle East Respiratory Syndrome (MERS), healthcare workers (HCWs) are at risk of acquiring and subsequently transmitting this lethal virus. In view of this, HCWs were evaluated for their knowledge of and attitude towards MERS in Saudi Arabia. A cross sectional study was performed in two hospitals of Qassim region in Saudi Arabia. A total of 280 healthcare workers were selected to participate in this study. Knowledge and attitude were assessed by using self-administered and pretested questionnaire. Descriptive statistics were carried out to express participants' demographic information, mean knowledge score and mean attitude score of HCWs. Inferential statistics (Mann-Whitney U test and Kruskal Wallis tests, p < 0.05) were used to examine differences between study variables. Chi squares tests were used to assess the association between study variables and attitude questions. Spearman's rho correlation was used to identify the association between the knowledge, attitude scores. Participants demonstrated good knowledge and positive attitude towards MERS. The mean scores of knowledge and attitude were 9.45 ± 1.69 (based on 13 knowledge questions) and 1.82 ± 0.72 (based on 7 attitude questions). The correlation between knowledge and attitude was significant (correlation coefficient: 0.12; P <0.001). HCWs were less educated about the management (42.4%), source (66%) and consequences of MERS (67.3%), while a majority of them were well aware of the hallmark symptoms (96%), precautionary measures (96%) and hygiene issues (94%). Although the majority of respondents showed positive attitude towards the use of protective measures (1.52 ± 0.84), their attitude was negative towards their active participation in infection control program (2.03 ± 0.97). Gender and experience were significantly associated with knowledge and attitude (P < 0.05). The findings of this study showed that healthcare workers in Qassim region of Saudi Arabia have good knowledge and positive attitude towards MERS. Yet there are areas where low knowledge and negative attitude of HCWs was observed. However, studies are required to assess the knowledge and attitude of HCWs at national level so that effective interventions could be designed as surveillance and infection control measures are critical to global public health.