Comparison of postoperative immune function in patients with thoracic esophageal cancer after video-assisted thoracoscopic surgery or conventional open esophagectomy.
The aim of the study was to compare postoperative immune function in patients with thoracic esophageal cancer (EC) after video-assisted thoracoscopic surgery (VATS) or conventional open esophagectomy. Medical records were retrospectively analyzed for 228 patients with thoracic EC treated at a single hospital using VATS (n = 52) or conventional open esophagectomy (n = 176). Proportions of CD3(+), CD4(+), CD8(+), and natural kill (NK) cells, as well as the ratio of CD4(+) to CD8(+) cells, were measured in the two groups using flow cytometry on preoperative day (PrD) 1 and postoperative days (PoD) 1 and 7. Proportions of CD3(+), CD4(+), and NK cells as well as the CD4+/CD8+ ratio decreased significantly from PrD1 to PoD1 in both the VATS and open esophagectomy groups. In the VATS group, these parameters had returned to preoperative levels (PrD1) by PoD7. These parameters in open esophagectomy group increased from PoD1 to PoD7 but also lowered significantly to PrD1 by PoD7. The proportion of CD8(+) cells was similar between the two groups at all time points tested. Patients may experience less postoperative immune suppression after VATS than after conventional open esophagectomy, and they may recover preoperative immune function more quickly.


Heavy involvement of stringent transcription control depending on the adenine or guanine species of the transcription initiation site in glucose and pyruvate metabolism in Bacillus subtilis.
In Bacillus subtilis cells, the GTP level decreases and the ATP level increases upon a stringent response. This reciprocal change in the concentrations of the substrates of RNA polymerase affects the rate of transcription initiation of certain stringent genes depending on the purine species at their transcription initiation sites. DNA microarray analysis suggested that not only the rrn and ilv-leu genes encoding rRNAs and the enzymes for synthesis of branched-chain amino acids, respectively, but also many genes, including genes involved in glucose and pyruvate metabolism, might be subject to this kind of stringent transcription control. Actually, the ptsGHI and pdhABCD operons encoding the glucose-specific phosphoenolpyruvate:sugar phosphotransferase system and the pyruvate dehydrogenase complex were found to be negatively regulated, like rrn, whereas the pycA gene encoding pyruvate carboxylase and the alsSD operon for synthesis of acetoin from pyruvate were positively regulated, like ilv-leu. Replacement of the guanine at position 1 and/or position 2 of ptsGHI and at position 1 of pdhABCD (transcription initiation base at position 1) by adenine changed the negative stringent control of these operons in the positive direction. The initiation bases for transcription of pdhABCD and pycA were newly determined. Then the promoter sequences of these stringent operons were aligned, and the results suggested that the presence of a guanine(s) and the presence of an adenine(s) at position 1 and/or position 2 might be indispensable for negative and positive stringent control, respectively. Such stringent transcription control that affects the transcription initiation rate through reciprocal changes in the GTP and ATP levels likely occurs for numerous genes of B. subtilis.


Consistent Model of Ultrafast Energy Transfer in Peridinin Chlorophyll-a Protein Using Two-Dimensional Electronic Spectroscopy and Förster Theory.
Solar light harvesting begins with electronic energy transfer in structurally complex light-harvesting antennae such as the peridinin chlorophyll-a protein from dinoflagellate algae. Peridinin chlorophyll-a protein is composed of a unique combination of chlorophylls sensitized by carotenoids in a 4:1 ratio, and ultrafast spectroscopic methods have previously been utilized in elucidating their energy-transfer pathways and timescales. However, due to overlapping signals from various chromophores and competing pathways and timescales, a consistent model of intraprotein electronic energy transfer has been elusive. Here, we used a broad-band two-dimensional electronic spectroscopy, which alleviates the spectral congestion by dispersing excitation and detection wavelengths. Interchromophoric couplings appeared as cross peaks in two-dimensional electronic spectra, and these spectral features were observed between the peridinin S2 states and chlorophyll-a Qx and Qy states. In addition, the inherently high time and frequency resolutions of two-dimensional electronic spectroscopy enabled accurate determination of the ultrafast energy-transfer dynamics. Kinetic analysis near the peridinin S1 excited-state absorption, which forms in 24 fs after optical excitation, reveals an ultrafast energy-transfer pathway from the peridinin S2 state to the chlorophyll-a Qx state, a hitherto unconfirmed pathway critical for fast interchromophoric transfer. We propose a model of ultrafast peridinin chlorophyll-a protein photophysics that includes (1) a conical intersection between peridinin S2 and S1 states to explain both the ultrafast peridinin S1 formation and the residual peridinin S2 population for energy transfer to chlorophyll-a, and (2) computationally and experimentally derived peridinin S2 site energies that support the observed ultrafast peridinin S2 to chlorophyll-a Qx energy transfer.


Neural representation of consciously imperceptible speech sound differences.
The concept of subliminal perception has been a subject of interest and controversy for decades. Of interest in the present investigation was whether a neurophysiologic index of stimulus change could be elicited to speech sound contrasts that were consciously indiscriminable. The stimuli were chosen on the basis of each individual subject's discrimination threshold. The speech stimuli (which varied along an F3 onset frequency continuum from /da/ to /ga/) were synthesized so that the acoustical properties of the stimuli could be tightly controlled. Subthreshold and suprathreshold stimuli were chosen on the basis of behavioral ability demonstrated during psychophysical testing. A significant neural representation of stimulus change, reflected by the mismatch negativity response, was obtained in all but 1 subject in response to subthreshold stimuli. Grand average responses differed significantly from responses obtained in a control condition consisting of physiologic responses elicited by physically identical stimuli. Furthermore, responses to suprathreshold stimuli (close to threshold) did not differ significantly from subthreshold responses with respect to latency, amplitude, or area. These results suggest that neural representation of consciously imperceptible stimulus differences occurs and that this representation occurs at a preattentive level.


Primary care-based models of care for osteoarthritis: a scoping review protocol.
Background: The burden of osteoarthritis (OA) to individuals and health systems is substantial and is expected to increase due to population ageing and rising prevalence of obesity and multimorbidity. Primary care-based models of care (MoCs) are being increasingly developed in response to this growing burden. However, these MoCs have yet to be formally reviewed. A MoC can be defined as an 'evidence-informed strategy, framework or pathway that outlines the optimal manner in which condition-specific care should be delivered to consumers within a local health system'. Objective: To identify and describe the available research regarding the extent, nature and characteristics of MoCs for OA that have been developed or evaluated in primary care. Methods: A scoping review will be conducted in accordance with the Arksey and O'Malley scoping review framework and the PRISMA-ScR guidelines. Systematic literature searches of MEDLINE, EMBASE, CINAHL, PsychINFO, Web of Science and LILACs will be conducted from 2010 to present, aligning with publication dates of recent clinical guidelines. A structured iterative search of grey literature will be conducted. Full-text original quantitative or mixed method studies which describe the development or evaluation of MoCs for OA in primary care will be considered. Data will be charted and synthesised and a narrative synthesis will be conducted. Conclusions: This scoping review will provide a broad overview regarding the extent, nature and characteristics of the available literature on primary care based MoCs for OA. Findings will be used to identify gaps in the current evidence to identify areas for future research.


The isolation, characterization and sequence of two divergent β-tubulin genes from soybean (Glycine max L.).
Two divergent β-tubulin genes (designated Sβ-1 and Sβ-2) were isolated by screening a soybean genomic library with a Chlamydomonas reinhardtii β-tubulin cDNA probe. Restriction fragment analysis of the clones recovered, and of soybean genomic DNA, indicated that these represent two unique classes of structurally different β-tubulin genes in the soybean genome. However, it is possible that unidentified members of these classes or additional highly divergent classes of β-tubulin genes (thus far undetected) exist in the soybean genome. The Sβ-1 and Sβ-2 genomic clones were sequenced, revealing that both are potentially functional genes which would encode β-tubulins of 445 and 449 amino acids, respectively. A comparison of their derived amino acid sequences with β-tubulins from several organisms showed that they are most homologous to Chlamydomonas β-tubulin (85-87%), with lesser degrees of homology to β-tubulins of vertebrate species (79-83%), Trypanosoma brucei (80-81%) and Saccharomyces cerevisiae (66-68%). The amino acid sequences of Sβ-1 and Sβ-2 are as divergent from each other as they are from the Chlamydomonas β-tubulin. The amino acids at the diverged positions in Sβ-2 are nearly all conservative substitutions while in Sβ-1, 18 of the 69 substitutions were non-conservative. Both soybean β-tubulin genes contain two introns in exactly the same positions. The first soybean intron is located in the same position as the third intron of the Chlamydomonas β-tubulin genes. Codon usage in the two soybean β-tubulins is remarkably similar (D (2)=0.87), but differs from codon usage in other soybean genes.


Ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS): an international cohort study.
There is much uncertainty about the risks of leukaemia and lymphoma after repeated or protracted low-dose radiation exposure typical of occupational, environmental, and diagnostic medical settings. We quantified associations between protracted low-dose radiation exposures and leukaemia, lymphoma, and multiple myeloma mortality among radiation-monitored adults employed in France, the UK, and the USA. We assembled a cohort of 308,297 radiation-monitored workers employed for at least 1 year by the Atomic Energy Commission, AREVA Nuclear Cycle, or the National Electricity Company in France, the Departments of Energy and Defence in the USA, and nuclear industry employers included in the National Registry for Radiation Workers in the UK. The cohort was followed up for a total of 8.22 million person-years. We ascertained deaths caused by leukaemia, lymphoma, and multiple myeloma. We used Poisson regression to quantify associations between estimated red bone marrow absorbed dose and leukaemia and lymphoma mortality. Doses were accrued at very low rates (mean 1.1 mGy per year, SD 2.6). The excess relative risk of leukaemia mortality (excluding chronic lymphocytic leukaemia) was 2.96 per Gy (90% CI 1.17-5.21; lagged 2 years), most notably because of an association between radiation dose and mortality from chronic myeloid leukaemia (excess relative risk per Gy 10.45, 90% CI 4.48-19.65). This study provides strong evidence of positive associations between protracted low-dose radiation exposure and leukaemia. Centers for Disease Control and Prevention, Ministry of Health, Labour and Welfare of Japan, Institut de Radioprotection et de Sûreté Nucléaire, AREVA, Electricité de France, National Institute for Occupational Safety and Health, US Department of Energy, US Department of Health and Human Services, University of North Carolina, Public Health England.


[New Perspectives in Post-Surgical Acute Kidney Injury During Sepsis].
Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. Sepsis is a common complication in patients undergoing surgery and is a major risk factor for the development of acute kidney injury (SA-AKI). Prevention of AKI in surgery patients is largely based on identification of high baseline risk, monitoring, and reduction of nephrotoxic insults. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches.


Role of hydrogen sulfide in the pathology of inflammation.
Hydrogen sulfide (H2S) is a well-known toxic gas that is synthesized in the human body from the amino acids cystathionine, homocysteine, and cysteine by the action of at least two distinct enzymes: cystathionine-γ-lyase and cystathionine-β-synthase. In the past few years, H2S has emerged as a novel and increasingly important biological mediator. Imbalances in H2S have also been shown to be associated with various disease conditions. However, defining the precise pathophysiology of H2S is proving to be a complex challenge. Recent research in our laboratory has shown H2S as a novel mediator of inflammation and work in several groups worldwide is currently focused on determining the role of H2S in inflammation. H2S has been implicated in different inflammatory conditions, such as acute pancreatitis, sepsis, joint inflammation, and chronic obstructive pulmonary disease (COPD). Active research on the role of H2S in inflammation will unravel the pathophysiology of its actions in inflammatory conditions and may help develop novel therapeutic approaches for several, as yet incurable, disease conditions.


Traditional Chinese and Indian medicine in the treatment of opioid-dependence: a review.
In this study, the current literatures on the use of herbs and herbal preparations of Traditional Chinese and Indian Medicine for the treatment of opioid addiction were reviewed. Matherials and Methods: Search was done in databases such as Pub Med, Science Direct, Scopus, Springer Link, and Google Scholar. Among 18 retrieved studies, 3 studies were about asafetida extract, an approved preparation for ameliorating drug abstinence in China. Chinese preparations including Composite Dong Yuan Gao, Qingjunyin and TJ-97 (a water extract of dai-bofu-to) as well as Indian ones, Mentate and Shilajit, were reported to have positive effects against opioid withdrawal, dependence, and tolerance. Moreover, Levo-tetrahydropalmatine and L-Stepholidine, in addition to extracts of Caulis Sinomenii and Sinomenium acutum showed similar effects. Banxia Houpu Decoction, Fu-Yuan pellet, Jinniu capsules, Qingjunyin, Tai-Kang-Ning capsule, and Xuan Xia Qudu Jiaonang (WeiniCom) from Chinese preparations, showed anti-addiction effects in randomized, double-blind and, in some studies, multicenter clinical trials. Conclusion : Traditional herbal preparations of China and India have anti-addiction effects with less adverse effects than alpha2-adrenergic or opioid agonists.


Capturing PM2.5 Emissions from 3D Printing via Nanofiber-based Air Filter.
This study investigated the feasibility of using polycaprolactone (PCL) nanofiber-based air filters to capture PM2.5 particles emitted from fused deposition modeling (FDM) 3D printing. Generation and aggregation of emitted particles were investigated under different testing environments. The results show that: (1) the PCL nanofiber membranes are capable of capturing particle emissions from 3D printing, (2) relative humidity plays a signification role in aggregation of the captured particles, (3) generation and aggregation of particles from 3D printing can be divided into four stages: the PM2.5 concentration and particles size increase slowly (first stage), small particles are continuously generated and their concentration increases rapidly (second stage), small particles aggregate into more large particles and the growth of concentration slows down (third stage), the PM2.5 concentration and particle aggregation sizes increase rapidly (fourth stage), and (4) the ultrafine particles denoted as "building unit" act as the fundamentals of the aggregated particles. This work has tremendous implications in providing measures for controlling the particle emissions from 3D printing, which would facilitate the extensive application of 3D printing. In addition, this study provides a potential application scenario for nanofiber-based air filters other than laboratory theoretical investigation.


Seasonal variation of strongylosis in working donkeys of Ethiopia: a cross-sectional and longitudinal studies.
Helminths are one of the major health problems of working donkeys, often with heavy worm burden and contributing to their early demise and/or reduction in their work output. Cross-sectional and longitudinal studies were conducted to investigate the current infection prevalence and level of strongyles infection donkeys would acquire through different seasons in the mid-lowland agro-ecological zones of Ethiopia. For this purpose, faecal samples from 206 (cross-sectional study) and 102 (longitudinal study) randomly selected donkeys were directly collected from the rectum and analysed. For the longitudinal study, the 102 donkeys dewormed at the end of main rainy season, beginning of October, were monitored for the level of strongyle infection they would acquire during subsequent dry and short rainy seasons. The cross-sectional study of 206 donkey has revealed an overall infection prevalence of 89.3% (95% confidence interval (CI) = 84.4, 92.9). Donkeys in the lowland zone showed a significantly higher strongyle infection prevalence (P = 0.0126) and mean eggs per gramme of faces (EPG) (P = 0.001; 2775 EPG) compared to donkeys in the midland zone (980.8 EPG). Age, sex and body condition did not have any significant effect on either the infection prevalence or level of infection (P > 0.05). The longitudinal study has shown a significantly lower strongyle infection prevalence (P = 0.003) and level of infection donkeys acquired (P = 0.001) in the subsequent dry and short rainy seasons compared to the main rainy season following October deworming. However, these values were not significantly different between the two agro-ecological zones (P > 0.05). This study clearly showed that parasitic infections are primarily acquired during the main rainy season when pasture/herbage coverage is relatively better, and the environment is conducive for parasites survival and development. On the other hand, the finding of majority of donkeys shedding low or no eggs during the dry and short rainy seasons showed that October deworming was effective, and donkeys acquire low or no parasitic infection during the subsequent dry and short rainy seasons. Therefore, the practice of anthelmintic treatment of donkeys at the end of short rain in May may not be necessary, and October deworming once a year is sufficient.


Catalytic Formation of Disulfide Bonds in Peptides by Molecularly Imprinted Microgels at Oil/Water Interfaces.
This work describes the preparation and investigation of molecularly imprinted polymer (MIP) microgel (MG) stabilized Pickering emulsions (PEs) for their ability to catalyze the formation of disulfide bonds in peptides at the O/W interface. The MIP MGs were synthesized via precipitation polymerization and a programmed initiator change strategy. The MIP MGs were characterized using DLS analysis, SEM measurement, and optical microscopy analysis. The dry and wet MIP MGs showed a hydrodynamic diameter of 100 and 280 nm, respectively. A template rebinding experiment showed that the MIP MGs bound over two times more template (24 mg g-1) compared to the uptake displayed by a nonimprinted reference polymer (NIP) MG (10 mg g-1) at saturation. Using the MIP MGs as stabilizers, catalytic oxidation systems were prepared by emulsifying the oil phase and water phase in the presence of different oxidizing agents. During the cyclization, the isolation of the thiol precursors and the oxidizing reagents nonselectively decreased the formation of the byproducts, while the imprinted cavities on the MIP MGs selectively promoted the intramolecular cyclization of peptides. When I2 was used as the oxidizing agent, the MIP-PE-I2 system showed a product yield of 50%, corresponding to a nearly 2-fold increase compared to that of the nonimprinted polymer NIP-PE-I2 system (26%). We believe the interfacial catalysis system presented in this work may offer significant benefits in synthetic peptide chemistry by raising productivity while suppressing the formation of byproducts.


The usefulness of single-strand DNA conformation polymorphism analysis to detect mutations in protein C deficiency.
The standard approach for the molecular genetic analysis of protein C deficiency, polymerase chain reaction (PCR) amplification followed by direct sequencing, although very accurate, is time-consuming. The aim of this study is to investigate the usefulness of a simplified, time-saving screening method for the detection of protein C mutations consisting of the combination of multiplex PCR amplifications using the same primers that were designed for sequencing, followed by single-strand DNA conformation polymorphism (SSCP) electrophoresis analysis performed with one set of conditions. The study was designed in two phases. First, we tested six known point mutations located in different exons of the protein C gene by SSCP. Second, we prospectively studied nine patients with protein C deficiency type I using SSCP as the first screening technique. All the exons were amplified with a common PCR protocol, either as single fragments or as multiplex combinations of several of them. In the retrospective study, three out of the six point mutations were visible as a band shift: 40 T-->G (exon 2), 1432 C-->T (exon 3) and 7253 C-->T (exon 8). In the prospective analysis SSCP detected three different mutations. These mutations were: 6128 T-->C (exon 7), 6216 C-->T (exon 7) and in two probands 8631 C-->T (exon 9). In the five remaining patients we identified only two different mutations by direct sequencing: 6246 G-->A (exon 7) in two patients and 8589 G-->A (exon 9) in four patients. In summary, the results from both studies show that only 60% of all mutations can be detected using this simplified method. It also suggests that a multiple set of conditions, smaller PCR fragments, or both, should be used in order to achieve a sensitivity comparable to sequencing.


Silicone-coated thin film array cochlear implantation in a feline model.
Some limitations of cochlear implants can be attributed to a restricted spectral representation of sound provided by contemporary electrode arrays. Microfabricated high-density thin film array (TFA) technology enables a greater density of stimulating sites and, thus, a more complete spectral representation. Previous pilot cadaveric studies have documented insertion characteristics, although not electrical characteristics. Electrode evoked auditory brainstem response (ABR) testing in a feline model. Six healthy, normal hearing cats were unilaterally deafened and implanted with a silicone coated TFA, measuring 27.8 × 0.4 × 80μm (L × W × H). Monopolar stimulation of single electrodes was used to evoke a triple peaked ABR. Thresholds to evoke a minimal ABR were determined. All 6 cats underwent successful full insertion and activation. Thresholds to evoke minimal ABR's varied among implants ranging from 75 to 450 μA. Over the basal portion of the array, thresholds were either larger or unable to evoke an ABR. Two-thirds of the implants showed ABR's along the entire array, whereas the others evoked ABR's at the apical end and less robustly more basally. This may reflect increased distance of the electrodes from the modiolus, as the basal half of the array is narrower relative to the width of the scala. A tapered design to ensure array distance to modiolus is minimized may enable the basal half of the arrays to stimulate more consistently.


Comparative vector competence of Culex tarsalis and Culex quinquefasciatus from the coachella, imperial, and San Joaquin Valleys of California for St. Louis encephalitis virus.
St. Louis encephalitis (SLE) virus has continued to be active in the Colorado Desert region of Southern California (Coachella and Imperial Valleys) since 1973, while it has virtually disappeared from the Sacramento and San Joaquin Valleys of Central California. Consequently, comparative vector competence studies were undertaken from 1978 to 1981 to evaluate the susceptibility of populations of Culex quinquefasciatus and Culex tarsalis from the San Joaquin and Coachella/Imperial Valleys to oral infection with representative SLE viral strains from each geographical area. Culex quinquefasciatus females from both areas were equally susceptible to infection with both viral strains by the pledget and viremic chick feeding techniques. Although susceptibility profiles were similar by both feeding techniques, infection thresholds (i.e., ID50S) obtained with Cx. quinquefasciatus females were at least 10,000-fold lower when fed on viremic chicks than on virus soaked pledgets. Culex tarslis females from the two geographical areas were equally susceptible to infection with the indigenous viral strain by feeding on pledgets, and were uniformly more susceptible than sympatric populations of Cx. quinquefasciatus. Thus, differences observed in SLE viral activity in different geographical areas of California since 1973 cannot be explained by differences in the susceptibility of Cx. quinquefasciatus or Cx. tarsalis to oral infection with SLE virus.


Treatment outcomes of patients with tardive dyskinesia and chronic schizophrenia.
We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia (TD) and examined the course of TD. This analysis compared 200 patients with DSM-IV-defined schizophrenia and TD and 997 patients without TD, all of whom were randomly assigned to receive one of 4 second-generation antipsychotics. The primary clinical outcome measure was time to all-cause treatment discontinuation, and the primary measure for evaluating the course of TD was change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare treatment discontinuation between groups. Changes in Positive and Negative Syndrome Scale (PANSS) and neurocognitive scores were compared using mixed models and analysis of variance. Treatment differences between drugs in AIMS scores and all-cause discontinuation were examined for those with TD at baseline. Percentages of patients meeting criteria for TD postbaseline or showing changes in AIMS scores were evaluated with χ(2) tests. Data were collected from January 2001 to December 2004. Time to treatment discontinuation for any cause was not significantly different between the TD and non-TD groups (χ(2)(1) = 0.11, P = .743). Changes in PANSS scores were not significantly different (F(1,974) = 0.82, P = .366), but patients with TD showed less improvement in neurocognitive scores (F(1,359) = 6.53, P = .011). Among patients with TD, there were no significant differences between drugs in the decline in AIMS scores (F(3,151) = 0.32, P = .811); 55% met criteria for TD at 2 consecutive visits postbaseline, 76% met criteria for TD at some or all postbaseline visits, 24% did not meet criteria for TD at any subsequent visit, 32% showed a ≥ 50% decrease in AIMS score, and 7% showed a ≥ 50% increase in AIMS score. Schizophrenia patients with and without TD were similar in time to discontinuation of treatment for any cause and improvement in psychopathology, but differed in neurocognitive response. There were no significant differences between treatments in the course of TD, with most patients showing either persistence of or fluctuation in observable symptoms. clinicaltrials.gov Identifier: NCT00014001.


Pulmonary carbonic anhydrase in the human, monkey, and rat.
The distribution of carbonic anhydrase in the human, monkey, and rat lung was studied by the histochemical method of Hansson. High activity of this enzyme was demonstrated in the endothelium of pulmonary capillaries. In the human and the monkey lung enzyme activity was exhibited in the whole circumference of the capillaries, but in the rat enzyme activity is confined to capillary segments having close contact with alveolar epithelium forming the blood-air barrier. Staining was inhibited by 10 microM acetazolamide, but was not affected by 10 microM Cl 13,850, an inactive acetazolamide analogue. The location of carbonic anhydrase in the lung supports the idea that pulmonary carbonic anhydrase promotes CO2 elimination from the blood into the alveolar space. Its possible functions may be to act upon plasma to accelerate the conversion of HCO-3 to CO2 and to facilitate CO2 transport through the lung tissue.


Comparison of four rapid diagnostic tests, ELISA, microscopy and PCR for the detection of Giardia lamblia, Cryptosporidium spp. and Entamoeba histolytica in feces.
Microscopy is the diagnostic reference standard for the detection of parasites, but it is labor-intensive and requires experience. Rapid diagnostic tests (RDTs) can provide an alternative to microscopy. RDTs from four different manufacturers were compared to enzyme-linked immunosorbent assay (ELISA), microscopy and/or parasite-specific real-time PCR: ImmunoCardSTAT!®CGE (Meridian Bioscience Inc., Cincinnati, Ohio, USA) (A), Crypto/Giardia Duo-Strip (Coris Bioconcepts, Gembloux, Belgium) (B), RIDA®QUICK Cryptosporidium/Giardia/Entamoeba Combi (R-BioPharm, Darmstadt, Germany) (C) and Giardia/Cryptosporidium Quik Chek (Techlab Inc., Blacksburg, Virginia, USA) (D). Thirty frozen samples were analyzed retrospectively. For Giardia lamblia (n=12) and Cryptosporidium (n=12) sensitivities ranged from 58% (B), over 83% (A, C) to 100% (D) and from 92% (B) to 100% (A, C, D), respectively. Specificity for both G. lamblia and Cryptosporidium was 100% for all RDT brands. Sensitivity for Entamoeba histolytica (n=5) was 100%, while specificity reached 80% (A) to 88% (C). In a prospective study, fresh samples were tested. For G. lamblia (n=30), sensitivity ranged from 66% (B), over 79% (A) and 83% (C) to 100% (D) and specificity varied between 94% (D) and 100% (A, B, C). For Cryptosporidium (n=3), sensitivity was 100% for all brands except (B) (67%) and specificities were 95% (A, B), 98% (C) and 100% (D). E. histolytica (n=1) was detected by both (A) and (C), while specificity was 81% and 87% respectively. RDTs can be a valuable tool when microscopic expertise is poor and in remote and outbreak settings where other techniques are often not available and rapid diagnosis is required.


Group cognitive behaviour therapy for supported employment - Results of a randomized controlled cohort trial.
The merging of evidence-based interventions with supported employment programs are being increasingly studied, with encouraging results. The current study is aimed at determining the impact of a brief cognitive behaviour therapy group intervention adapted for supported employment programs (called CBT-SE) on the work outcomes of: obtaining a competitive job, number of weeks worked, and number of hours worked per week. Participants were randomized to either receive the 8-session CBT-SE group on top of their supported employment program, or to only receive their support employment program. The results show that those who received CBT-SE were significantly more likely to obtain a job (75% vs 58%), and worked a significantly greater number of hours (24 vs 18 hours per week). No differences were found in terms of number of weeks worked. Those in the CBT-SE condition also experienced a significant decrease in their negative symptoms over time, compared to the control condition. Although replication is needed, these results suggest that a brief cognitive-behavioural intervention specifically tailored to work-related issues can be greatly beneficial.


"Skeletal muscle function deficit" in a nationally representative British birth cohort in early old age.
Recommendations for identifying age-related muscle dysfunction have recently been published. We aimed to compare definitions for clinically relevant weakness and low lean mass proposed by the Foundation for the National Institutes of Health (FNIH) Sarcopenia project with the definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). A total of 1566 men and women from a British birth cohort had measures of appendicular lean mass, grip strength and timed up, and go speed at ages 60-64. Prevalence of low lean mass, weakness and slowness, identified using the FNIH and EWGSOP recommendations were estimated and compared: using kappa statistics and; by testing cross-sectional associations of both definitions of low lean mass and weakness with slowness and self-reported difficulties walking. The combined prevalence of low lean mass and weakness ranged from 1.1% in men using FNIH criteria to 6.4% in women using EWGSOP criteria. There was limited overlap between the groups identified using the different criteria, driven by limited agreement between the two definitions of low lean mass. Using FNIH criteria, both low lean mass and weakness were associated with higher odds of slowness and difficulties walking; whereas low lean mass classified using EWGSOP criteria was not associated with these markers of mobility impairment. At relatively young ages, signs of skeletal muscle function deficit with potential clinical relevance are already identifiable in the general population. This suggests that implementation of strategies to prevent mobility limitations, related to age-related muscle dysfunction, may need to start at least as early as midlife.


Intra-articular viscosupplementation with hylan g-f 20 to treat osteoarthritis of the knee: an evidence-based analysis.
To assess the effectiveness and cost-effectiveness of hylan G-F 20 as a substitute for existing treatments for pain due to osteoarthritis (OA) of the knee, other viscosupplementation devices, and/or as an adjunct to conventional therapy. Hylan G-F 20 (brand name Synvisc, which is manufactured by Genzyme) is a high molecular weight derivative of hyaluronan, a component of joint synovial fluid. It acts as a lubricant and shock absorber. It is administered by injection into the joint space to treat pain associated with OA of the knee. Although the injection procedure is an insured service in Ontario, the device, hylan G-F 20, is not. Osteoarthritis is prevalent in 10% to 12% of Ontario adults, and exceeds 40% in Ontario residents aged 65 years and older. About one-half of these people have mild, moderate, or severe OA of the knee. Conventional treatment involves a combination of nonpharmacological management (e.g., weight loss, exercise, social support, and patient education), drugs, (e.g., acetaminophen, COX-2 inhibitors, nonsteroidal anti-inflammatory drugs with/without misoprostol, intra-articular glucocorticoids, opioids, and topical analgesics) and surgical interventions, such as debridement and total knee replacement, when pharmacological management fails. The growing burden of OA of the knee in the aging Ontario population combined with recent safety concerns about COX-2 inhibitors and long wait times for total joint replacement is placing pressure on the demand for new, effective technologies to manage the pain of OA. Hylan G-F 20 is derived from rooster comb hyaluronan (HA). At the time of writing, eight viscosupplement hyaluronic products are licensed in Canada. Hylan G-F 20 is distinguished from the other products by its chemical structure (i.e., cross-linked hyaluronan, hence hylan) and relatively higher molecular weight, which may bestow greater therapeutic viscoelastic properties. A complete treatment cycle of hylan G-F 20 involves an intra-articular injection of 2 ml of hylan G-F 20 once a week for 3 weeks. It is licensed for use for patients in all stages of joint pathology, but should not be used in infected or severely inflamed joints, in joints with large effusion, in patients that have skin diseases or infections in the area of the injection site, or in patients with venous stasis. It is also contraindicated in patients with hypersensitivities to avian proteins. The Medical Advisory Secretariat used its standard search protocol to review the literature for evidence on the effectiveness of intra-articular hylan G-F 20 compared with placebo, as a substitute for alternate active treatments, or as an adjunct to conventional care for treatment of the pain of OA of the knee. All English-language journal articles and reviews with clearly described designs and methods (i.e., those sufficient to assign a Jadad score to) published or released between 1966 and February 2005 were included. Two more recently published meta-analyses were also included. The databases searched were Ovid MEDLINE, EMBASE, the Cochrane database and leading international organizations for health technology assessments, including the International Network of Agencies for Health Technology Assessments. The search terms were as follows: hyaluronan, hyaluronate adj sodium, hylan, hylan G-F 20 (Synvisc), Synvisc, Hyalgan, Orthovisc, Supartz, Artz, Artzal, BioHY, NASHA, NRD101, viscosupplementation, osteoarthritis, knee, knee joint. The primary outcome of interest was a clinically significant difference, defined as greater than 10 mm on 100 mm visual analogue scale, or a change from baseline of more than 20% in the mean magnitude of pain relief experienced among patients treated with hylan G-F 20 compared with those treated with the control intervention. One clinical epidemiologist reviewed the full-text reports and extracted data using an extraction form. Key variables included, but were not limited to, the characteristics of the patients, method of randomization, type of control intervention, outcome measures for effectiveness and safety, and length of follow-up. The quality of the studies and level of the evidence was initially scored by one clinical epidemiologist using the Jadad scale and GRADE approach. Level of quality depends on the amount of certainty about the magnitude of effect and is based on study designs, extent of methodological limitations, consistency of results and applicability (i.e. directness) to the Ontario clinical context. The GRADE approach also permits comment on the strength of recommendations resulting from the evidence, based on estimates of the magnitude of effect relative to the magnitude of risk and burden and the level of certainty around these estimates. The quality assessments were subsequently peer-reviewed. The literature search revealed 2 previous health technology assessments, 3 meta-analyses of placebo-controlled trials, 1 Cochrane review and meta-analysis encompassing 18 randomized controlled trials (RCTs) that compared hylan G-F 20 to either placebo or active treatments, 11 RCTs of hylan G-F 20 (all included in the Cochrane review), and 10 observational studies. Given the preponderance of evidence, the Medical Advisory Secretariat's analysis focused on studies with Level 1 evidence of effectiveness (i.e., the meta-analyses of RCTs and the RCTs). Only safety data from the observational studies were included. The authors of the 2 health technology assessments concluded that the data were sparse and poor quality. There was some evidence that hylan G-F 20 delivered a small, clinical benefit at 3 to 6 months after treatment on a magnitude comparable to NSAIDs and intra-articular steroids. Hylan G-F 20 appeared to carry a risk of a local adverse reaction of in the range of 3% to 18% per 100 injections, but there was no apparent risk of a severe adverse event, although the data were limited. Each of the 3 meta-analyses of placebo-controlled trials of intra-articular hyaluronans had only 3 trials involving hylan G-F 20. There results were inconsistent, with one study concluding that intra-articular hyaluronans were efficacious, whereas the 2 other analyses concluded the effect size was small (0.32) and probably not clinically significant. The risk of a minor adverse event ranged from 8% to 19% per 100 injections. Major adverse events were rare. The authors of the Cochrane review concluded that a pooled analysis supported the efficacy of hyaluronans, including hylan G-F 20. The 5- to 13-week post-injection period showed an improvement from baseline of 11% to 54% for pain and 9% to 15% for function. Comparable efficacy was noted against NSAIDs, and longer-term benefits were noted in against steroids. Few adverse events were noted. When the Medical Advisory Secretariat applied the criterion of clinical significance to the magnitude of pain relief reported in the RCTs on hylan G-F 20, the following was noted:There was inconsistent evidence that hylan G-F 20 was clinically superior to placebo at 5 to 26 weeks after treatment.There was consistent evidence that, in terms of delivering pain relief, hylan G-F 20 was no better or worse than NSAIDs or intra-articular steroids at 5 to 26 weeks after treatment.There was consistent evidence that hylan G-F 20 was not clinically superior to other hyaluronic products.There was consistent evidence that hylan G-F 20 delivered a small magnitude of clinical benefit at 12 to 52 weeks post-injection when administered as an adjunct to conventional care.There were limitations to the methods in many of the RCTs involving hylan G-F 20. When only the results from the higher-quality studies were considered, there was level 2 evidence that hylan G-F 20 was not clinically superior to placebo (or another hyaluronan) at 1 to 26 weeks after treatment in older patients with advanced disease for whom total knee replacement was indicated. There was level 2 evidence that hylan G-F 2- was comparable to NSAIDs at 4 to 13 weeks after treatment, and level 2 evidence that hylan G-F 20 was superior to placebo as an adjunct to conventional care 4 to 26 weeks after treatment. With respect to safety, overall, hylan G-F 20 carries a risk of a minor, local adverse event rate of about 8% to 19% per 100 injections. Incidents of moderate-severe post-injection inflammatory joint reactions have been reported, but the likelihood appears to be low (0.15% of patients). Case-costing estimates suggest that the annual cost of 2 treatment cycles of hylan G-F 20 (plus analgesics for breakthrough pain) is almost equivalent to the annual cost of taking a NSAID (with a gastroprotective agent) and is more expensive that taking intra-articular corticosteroids (plus analgesics for breakthrough pain). The estimated cost of funding hylan G-F 20 as an adjunct to conventional therapy (i.e., any of analgesics, NSAIDs, intra-articular steroids, physiotherapy, and surgery) is $700 per patient per year. Given the huge burden of mild to moderate OA among adults who seek medical care for it in Ontario (about 300,000), funding hylan G-F 20 as an adjunct to existing treatment could be expensive, depending on its diffusion and uptake. If only 10% to 30% of patients choose this option, then the estimated budget impact would be $21 million to $63 million (Cdn) per year. When the benefits relative to the risks and costs are considered, NSAIDs and hylan G-F 20 appear comparable, as the table shows. Consequently, there's little evidence on which to recommend hylan G-F 20 over NSAIDs, except perhaps for patients who cannot tolerate NSAIDs, although this evidence is indirect, since no studies looked specifically at this population. (ABSTRACT TRUNCATED)


In-line rainbow trapping based on plasmonic gratings in optical microfibers.
In-line rainbow trapping is demonstrated in an optical microfiber with a plasmonic grating. The dispersions of x- and y-polarized surface plasmon polariton (SPP) modes are analyzed in detail by the 3D finite element method (FEM). In this system, the incident light is coupled from an optical microfiber into a graded grating. The plasmonic structure shows strong localization as the dispersion curve approaches cut-off frequency. Gradually increasing the depth or width of the grating elements ensures that the cut-off frequency of the SPP mode varies with the position along the microfiber. Near-infrared light at different frequencies can be trapped in different spatial positions. The in-line rainbow trapping is important for potential applications including optical storage, slow light, optical switch and enhanced light-matter interactions in fiber integrated devices and highly integrated optical circuits.


Correlation between prefrontal cortex activity during working memory tasks and natural mood independent of personality effects: an optical topography study.
Interactions between mood and cognition have drawn much attention in the fields of psychology and neuroscience. Recent neuroimaging studies have examined a neural basis of the mood-cognition interaction that which emphasize the role of the prefrontal cortex (PFC). Although these studies have shown that natural mood variations among participants are correlated with PFC activity during cognitive tasks, they did not control for personality differences. Our aim in this study was to clarify the relationship between natural mood and PFC activity by partialling out the effects of personality. Forty healthy adults completed self-report questionnaires assessing natural mood (the Profile of Mood States) and personality (the NEO Five-Factor Inventory and the Behavioral Inhibition/Activation Systems scales). They performed verbal and spatial working memory (WM) tasks while their PFC activity was measured using optical topography, a non-invasive, low-constraint neuroimaging tool. Correlation analysis showed that the level of negative mood was inversely associated with PFC activity during the verbal WM task, which replicated our previous findings. Furthermore, the negative correlation between negative mood and PFC activity remained significant after controlling for participants' personality traits, suggesting that natural mood is an independent contributing factor of PFC activity during verbal WM tasks.


An overview of regional and local characteristics of aerosols in South Africa using satellite, ground, and modeling data.
We present a comprehensive overview of particulate air quality across the five major metropolitan areas of South Africa (Cape Town, Bloemfontein, Johannesburg and Tshwane (Gauteng Province), the Industrial Highveld Air Quality Priority Area (HVAPA), and Durban), based on a decadal (1 January 2000 to 31 December 2009) aerosol climatology from multiple satellite platforms and detailed analysis of ground-based data from 19 sites throughout Gauteng Province. Satellite analysis was based on aerosol optical depth (AOD) from MODIS Aqua and Terra (550 nm) and MISR (555 nm) platforms, Ångström Exponent (α) from MODIS Aqua (550/865 nm) and Terra (470/660 nm), ultraviolet aerosol index (UVAI) from TOMS, and results from the Goddard Ozone Chemistry Aerosol Radiation and Transport (GOCART) model. At continentally influenced sites, AOD, α, and UVAI reach maxima (0.12-0.20, 1.0-1.8, and 1.0-1.2, respectively) during austral spring (September-October), coinciding with a period of enhanced dust generation and the maximum integrated intensity of close-proximity and subtropical fires identified by MODIS Fire Information for Resource Management System (FIRMS). Minima in AOD, α, and UVAI occur during winter. Results from ground monitoring indicate that low-income township sites experience by far the worst particulate air quality in South Africa, with seasonally averaged PM10 concentrations as much as 136 % higher in townships that in industrial areas. We report poor agreement between satellite and ground aerosol measurements, with maximum surface aerosol concentrations coinciding with minima in AOD, α, and UVAI. This result suggests that remotely sensed data are not an appropriate surrogate for ground air quality in metropolitan South Africa.


Back schools for nonspecific low back pain: a systematic review within the framework of the Cochrane Collaboration Back Review Group.
A systematic review within the Cochrane Collaboration Back Review Group. To assess the effectiveness of back schools for patients with nonspecific low back pain (LBP). Since the introduction of the Swedish back school in 1969, back schools have frequently been used for treating patients with LBP. However, the content of back schools has changed and appears to vary widely today. We searched the MEDLINE and EMBASE databases and the Cochrane Central Register of Controlled Trials to November 2004 for relevant trials reported in English, Dutch, French, or German. We also screened references from relevant reviews and included trials. Randomized controlled trials that reported on any type of back school for nonspecific LBP were included. Four reviewers, blinded to authors, institution, and journal, independently extracted the data and assessed the quality of the trials. We set the high-quality level, a priori, at a trial meeting six or more of 11 internal validity criteria. Because data were clinically and statistically too heterogeneous to perform a meta-analysis, we used a qualitative review (best evidence synthesis) to summarize the results. The evidence was classified into four levels (strong, moderate, limited, or no evidence), taking into account the methodologic quality of the studies. We also evaluated the clinical relevance of the studies. Nineteen randomized controlled trials (3,584 patients) were included in this updated review. Overall, the methodologic quality was low, with only six trials considered to be high-quality. It was not possible to perform relevant subgroup analyses for LBP with radiation versus LBP without radiation. The results indicate that there is moderate evidence suggesting that back schools have better short- and intermediate-term effects on pain and functional status than other treatments for patients with recurrent and chronic LBP. There is moderate evidence suggesting that back schools for chronic LBP in an occupational setting are more effective than other treatments and placebo or waiting list controls on pain, functional status, and return to work during short- and intermediate-term follow-up. In general, the clinical relevance of the studies was rated as insufficient. There is moderate evidence suggesting that back schools, in an occupational setting, reduce pain and improve function and return-to-work status, in the short- and intermediate-term, compared with exercises, manipulation, myofascial therapy, advice, placebo, or waiting list controls, for patients with chronic and recurrent LBP. However, future trials should improve methodologic quality and clinical relevance and evaluate the cost-effectiveness of back schools.


Membrane-Anchoring, Comb-Like Pseudopeptides for Efficient, pH-Mediated Membrane Destabilization and Intracellular Delivery.
Endosomal release has been identified as a rate-limiting step for intracellular delivery of therapeutic agents, in particular macromolecular drugs. Herein, we report a series of synthetic pH-responsive, membrane-anchoring polymers exhibiting dramatic endosomolytic activity for efficient intracellular delivery. The comb-like pseudopeptidic polymers were synthesized by grafting different amounts of decylamine (NDA), which act as hydrophobic membrane anchors, onto the pendant carboxylic acid groups of a pseudopeptide, poly(l-lysine iso-phthalamide). The effects of the hydrophobic relatively long alkyl side chains on aqueous solution properties, cell membrane destabilization activity, and in-vitro cytotoxicity were investigated. The optimal polymer containing 18 mol % NDA exhibited limited hemolysis at pH 7.4 but induced nearly complete membrane destabilization at endosomal pH within only 20 min. The mechanistic investigation of membrane destabilization suggests the polymer-mediated pore formation. It has been demonstrated that the polymer with hydrophobic side chains displayed a considerable endosomolytic ability to release endocytosed materials into the cytoplasm of various cell lines, which is of critical importance for intracellular drug delivery applications.


Vibrio bacteria in raw oysters: managing risks to human health.
The human-pathogenic marine bacteria Vibrio vulnificus and V. parahaemolyticus are strongly correlated with water temperature, with concentrations increasing as waters warm seasonally. Both of these bacteria can be concentrated in filter-feeding shellfish, especially oysters. Because oysters are often consumed raw, this exposes people to large doses of potentially harmful bacteria. Various models are used to predict the abundance of these bacteria in oysters, which guide shellfish harvest policy meant to reduce human health risk. Vibrio abundance and behaviour varies from site to site, suggesting that location-specific studies are needed to establish targeted risk reduction strategies. Moreover, virulence potential, rather than simple abundance, should be also be included in future modeling efforts.


Eating habits and attitudes of mothers of children with non-organic failure to thrive.
The eating habits and attitudes concerning body shape and weight among 26 mothers of children with non-organic failure to thrive (the index group) were studied using the eating disorder examination. They were compared with equivalent data on 26 individually matched women who participated in a large community survey. The index mothers' views of their child's weight and shape were also studied. The principal findings were, firstly, that when compared with the comparison group, mothers of children with non-organic failure to thrive had higher levels of dietary restraint. Secondly, despite their child's low weight, 50% of the index mothers were restricting their child's intake of 'sweet' foods, and a further 30% were restricting foods they considered 'fattening' or 'unhealthy'. These results raise the question of whether maternal eating habits and attitudes have a causal role in the genesis of non-organic failure to thrive. They suggest that careful inquiry about the mothers' eating habits and attitudes is needed when assessing children with non-organic failure to thrive.


Maternal smoking and fetal sex significantly affect metabolic enzyme expression in the human fetal liver.
Pollutants and toxicants passing from the mother to the fetus may damage developing organ systems. The human fetal liver is both a potential target organ and a critical defense against exposure to such xenochemicals. The aim of the study was to determine the effects of human fetal toxicant exposure, via maternal smoking, on metabolic enzyme transcripts in the fetal liver. We conducted an observational study of mRNA transcripts and proteins in livers from second trimester fetuses at the Universities of Aberdeen and Glasgow. Liver samples were taken from 55 normal fetuses from women undergoing second trimester elective termination. Housekeeping genes for normalization were identified by GeNorm and NormFinder. Levels of mRNA transcripts encoding 15 metabolic enzymes and three xenobiotic receptors were measured. Expression of representative proteins was shown by Western blotting. Eighty-nine percent of measured transcripts were detectable in the human fetal liver. Eight transcripts showed significant sex-specific differences in expression levels (EPHX1, GSTA1, GSTT1, AHR, AS3MT, GLRX2, GGT1, CAR). In male fetuses, maternal smoking was associated with a decrease in expression of three transcripts (GGT1, CYP2R1, CAR) and an increase in eight transcripts (CYP1A1, EPHX1, NQO1, GSTP1, GSTT1, AHR, AS3MT, GLRX2). In the female, CYP3A7 and EPHX1 were increased in smoke-exposed fetuses. The human fetal liver expresses a wide array of metabolic enzymes, with sex differences apparent in 44% of the transcripts measured. Exposure of the fetus to pollutants/toxicants is associated with significantly altered transcript expression, with the more marked response in the male potentially affecting levels of endogenous factors involved in fetal growth.


Tissue generation with growth factors.
An in vivo experimental model was introduced to determine whether the mitogenic effect of recombinant platelet-derived growth factor (rPDGF) could be used to generate potentially useful tissue. In Lewis rats, the extended femoral arteriovenous bundle was placed within silicone chambers containing collagen disks. The disks could deliver their content of rPDGF-BB (125 to 131 micrograms/disk) either as a rapid pulse or as a slow release. The time course of tissue generation was determined by harvesting the specimens at various postoperative days. The effect of continuous versus pulsed delivery was determined at 30 days. Analysis of the generated tissue was performed by use of histomorphometry. Pulsed delivery of rPDGF-BB induced the formation of a substantial amount of tissue that peaked at 10 to 15 days (145.9 +/- 13.8 vs 35.0 +/- 6.8 mm3, p < 0.0001); however, the generated tissue completely subsided by day 30. Sustained delivery of rPDGF-BB caused continuous growth of the tissue and was more effective than pulsed delivery. In an experimental model that approximates an in vivo tissue culture system, rPDGF-BB can induce a tenfold increase in tissue within the chamber. However, that tissue is labile and its survival necessitates continuous rPDGF-BB delivery. To become useful for reconstructive purposes, means to stabilize this new tissue growth are needed.


The Role of Butyrate on Monocyte Migration and Inflammation Response in Patient with Type 2 Diabetes Mellitus.
Type 2 Diabetes Mellitus (T2DM) is a very serious global problem. In Indonesia, this disease attacks at the most productive age; consequently, it can reduce economic status and life expectancy. The pathogenesis of T2DM is very closely related to inflammation and macrophage accumulation. However, no anti-inflammatory agent has been proven to play a role in the management of T2DM. Butyrate is a short chain fatty acid produced from resistant starch fermentation in the intestinal lumen. It is able to bind to GPR41 and GPR43 receptors on monocytes, so that it can change the pattern of cytokine expression, activation, migration and cell differentiation. Hence, it is interesting to examine the anti-inflammation effect of butyrate and the effect on monocyte migration. A total of 37 subjects were examined in this study. They were divided into two groups, with and without butyrate treatment. We analyzed two pro-inflammatory cytokines (Tumor Necrosis Factor TNF-α and Interleukin IL-6) and one anti-inflammatory cytokine, IL 10. Monocytes were isolated in type 1 collagen gel for migration testing using the µ-slide chemotaxis IBIDI. Image analysis used ImageJ and Chemotaxis tool software. There was a significant difference in the TNFα/IL 10 ratio between healthy groups and T2DM. Butyrate also appears to suppress TNFα cytokine production and increase IL10 production. It also decreases the accumulation distance of monocyte migration in T2DM.


Evidence for human immunodeficiency virus type 1 replication in vivo in CD14(+) monocytes and its potential role as a source of virus in patients on highly active antiretroviral therapy.
In vitro studies show that human immunodeficiency virus type 1 (HIV-1) does not replicate in freshly isolated monocytes unless monocytes differentiate to monocyte-derived macrophages. Similarly, HIV-1 may replicate in macrophages in vivo, whereas it is unclear whether blood monocytes are permissive to productive infection with HIV-1. We investigated HIV-1 replication in CD14(+) monocytes and resting and activated CD4(+) T cells by measuring the levels of cell-associated viral DNA and mRNA and the genetic evolution of HIV-1 in seven acutely infected patients whose plasma viremia had been <100 copies/ml for 803 to 1,544 days during highly active antiretroviral therapy (HAART). HIV-1 DNA was detected in CD14(+) monocytes as well as in activated and resting CD4(+) T cells throughout the course of study. While significant variation in the decay slopes of HIV-1 DNA was seen among individual patients, viral decay in CD14(+) monocytes was on average slower than that in activated and resting CD4(+) T cells. Measurements of HIV-1 sequence evolution and the concentrations of unspliced and multiply spliced mRNA provided evidence of ongoing HIV-1 replication, more pronounced in CD14(+) monocytes than in resting CD4(+) T cells. Phylogenetic analyses of HIV-1 sequences indicated that after prolonged HAART, viral populations related or identical to those found only in CD14(+) monocytes were seen in plasma from three of the seven patients. In the other four patients, HIV-1 sequences in plasma and the three cell populations were identical. CD14(+) monocytes appear to be one of the potential in vivo sources of HIV-1 in patients receiving HAART.


Cimetidine, an unexpected anti-tumor agent, and its potential for the treatment of glioblastoma (review).
Cimetidine (CIM), the prototypical histamine H2 receptor antagonist (H2RA), was brought to market based on its ability to accelerate healing of gastrointestinal ulcers through the inhibition of gastric acid secretion. Cimetidine, the most studied H2RA, has been demonstrated to possess anti-tumor activity against colon, gastric and kidney cancers, and melanomas. This activity involves a number of different mechanisms of action: a) CIM antagonizes tumor cell-mediated interleukin-1-induced activation of selectins in liver sinusoids, inhibiting tumor cell binding on liver sinusoids, thereby reducing the development of liver metastasis; b) histamine acts as a growth factor in various tumor cell types via the activation of H2 receptors; CIM therefore may antagonize this effect; c) CIM acts as an immunomodulator by enhancing the host's immune response to tumor cells. With respect to malignant gliomas, CIM added to temozolomide was superior in vivo when compared to temozolomide alone in extending survival of nude mice with human glioblastoma cells orthotopically xenografted into their brain. We review the various mechanisms of action potentially associated with the therapeutic effects of CIM in the case of experimental glioblastomas, observations we hope will encourage clinical investigation of CIM in the management of highly malignant gliomas.


A multicountry ecologic study of risk and risk reduction factors for prostate cancer mortality.
The objective of this research is to identify and determine the relative importance of dietary and environmental risk and risk reduction factors for prostate cancer mortality. A multicountry ecologic approach was used in multivariate regression analyses with prostate cancer mortality rates and dietary factors and solar ultraviolet-B (UV-B) radiation. Prostate cancer mortality rates for 32 predominantly Caucasian countries for the late 1990s were obtained from the World Health Organization. Dietary supply data were obtained from the Food and Agriculture Organization. Annual solar UV-B dose data were obtained from European ground stations and used to estimate values elsewhere. Linear and multiple linear regression analyses were conducted for all 32 countries as well as the 20 European countries. The strongest risk factor for prostate cancer mortality was animal products, with the nonfat portion of milk and alcohol being somewhat weaker; the strongest risk reduction factors were onions, other protective vegetable products (excluding alcohol, oils, and sweeteners), and solar UV-B radiation. Dietary data for 1979-81 yielded the highest correlations. These results are consistent with insulin-like growth factor-I (IGF-I), being an important risk factor for prostate cancer, with alcohol and calcium being less important risk factors, and with allium family vegetables, and, to a lesser extent, vitamin D being important risk reduction factors. These results should provide guidance for additional studies on dietary and environmental links to prostate cancer.


A reporter system for assaying influenza virus RNP functionality based on secreted Gaussia luciferase activity.
Influenza A virus can infect a wide variety of animal species including humans, pigs, birds and other species. Viral ribonucleoprotein (vRNP) was involved in genome replication, transcription and host adaptation. Currently, firefly luciferase (Fluc) reporter system was used in vRNP functional assay. However, its limitation for the testing by virus infection resulted in an increased need for rapid, sensitive, and biosafe techniques. Here, an influenza A virus UTR-driven gene reporter for vRNP assay based on secreted Gaussia luciferase (Gluc) activity was evaluated. By measuring Gluc levels in supernatants, reporter gene activity could be detected and quantitated after either reconstitution of influenza A virus polymerase complex or viral infection of 293T and A549 cells, respectively. As compared with Fluc reporter, Gluc-based reporter was heat-tolerant (65°C for 30 min) and produced 50-fold higher bioluminescent activity at 24 h posttransfection. Signals generated by Gluc reporter gene could be detected as early as 6 h post-infection and accumulated with time. Testing by viral infection, stronger signals were detected by Gluc reporter at a MOI of 0.001 than that of 1 and the effects of PB2-627K/E or amantadine on influenza vRNP activity were elucidated more effectively by the Gluc reporter system. This approach provided a rapid, sensitive, and biosafe assay of influenza vRNP function, particularly for the highly pathogenic avian influenza viruses.


Spatial localization of sound elicits early responses from occipital visual cortex in humans.
Much evidence points to an interaction between vision and audition at early cortical sites. However, the functional role of these interactions is not yet understood. Here we show an early response of the occipital cortex to sound that it is strongly linked to the spatial localization task performed by the observer. The early occipital response to a sound, usually absent, increased by more than 10-fold when presented during a space localization task, but not during a time localization task. The response amplification was not only specific to the task, but surprisingly also to the position of the stimulus in the two hemifields. We suggest that early occipital processing of sound is linked to the construction of an audio spatial map that may utilize the visual map of the occipital cortex.


Regular exercise improves weight stability in patients with advanced heart failure.
The purpose of this study was to determine if a progressive, prescribed home-based aerobic exercise program would alter the natural physiological processes that maintain fluid balance stability in patients with New York Heart Association (NYHA) class III/IV heart failure after medical optimization (titration of oral medical therapy with or without the infusion of an intravenous inotrope). A total of 56 men and women from a large tertiary trauma I hospital were enrolled with 56 subjects contributing to baseline analysis and 42 subjects at 24 weeks. Subjects were diagnosed with heart failure via NYHA classification IV or III for at least 6 months and were hospitalized for a current acute decompensation exacerbation in which they were being medically optimized. The exercise intervention was a home-based, prescribed, progressive aerobic exercise program lasting for 24 weeks. The exercise participants had weekly phone calls to gather data and progress the exercise program and one 12-week follow up. The usual care participants received random phone calls to collect data and had one 12-week follow up visit to attain physical assessment values. Subjects were primarily female (59%), nonwhite (54%), and NYHA class IV (52%) versus class III (48%). The mean age was 58 years (±11.8 years). The subjects had a mean ejection fraction of 17.7 % (±7%) and mean maximal oxygen consumption of 12.1 (±3.4). Using a hierarchical multiple regression model, it was demonstrated that an exercise prescription (intensity, frequency, duration) significantly predicted 24 h weight fluctuations within a NYHA class III/IV heart failure population after medical optimization (R(2) linear = 0.713, F = 3.224, p = 0.015). This study demonstrated that exercise is a successful adjunctive therapy to managing the daily weight variability or fluid status instability of patients with NYHA class III/IV heart failure that is often a debilitating aspect of the syndrome.


Effects of Greenfall on Ground-dwelling Arthropods in a Subtropical Forest.
Chien-Lung Chen and Pei-Jen L. Shaner (2018) Resource events such as typhoon-triggered greenfall have consequences for multiple ecological mechanisms, ranging from population dynamics and trophic interactions to ecosystem processes. Arthropods are sensitive to environmental disturbances, and many taxa have been used as indicator species. In a field experiment, we tested the effects of greenfall on ground-dwelling arthropods (mostly litter-dwelling taxa) in a forest of Taiwan red pine (Pinus taiwanensis) in the summer of 2013. Of 20 field plots (5 × 5 m), half received P. taiwanensis greenfall while the other half served as unaltered controls. As predicted, some arthropod taxa responded more strongly than others to the greenfall addition. Among the examined arthropod taxa (Araneae, Coleoptera: Carabidae, Coleoptera: Staphylinidae, Hymenoptera: Formicidae, Collembola, Isopoda: Oniscidea), the predatory staphylid beetles (Staphylinidae) responded positively to greenfall addition while the larger-sized detritivore woodlice (Oniscidea) responded negatively. Contrary to our prediction of a positive response, the smaller-sized detritivore springtails (Collembola) were unaffected by the greenfall addition. At the beginning of this study, we observed short-term effects of a naturally- occurring typhoon, to which springtails and ants (Formicidae) responded negatively while staphylid beetles responded positively. Also contrary to our prediction, these taxon-specific responses did not suffice to alter the composition of arthropod communities. We concluded that the intra-annual effects of typhoons-specifically those associated with greenfall-are more likely to impact certain taxa, including staphylid beetles, woodlice, springtails and ants. At the taxonomic level examined here, these intra-annual effects on community composition are non-detectable. As typhoon frequency and intensity are likely to change with global warming, the study makes a timely contribution to our understanding of typhoon-induced ecological dynamics in subtropical plantation forests.


Review of Ethnobotanical, Phytochemical, and Pharmacological Study of Thymus serpyllum L.
Thymus serpyllum L. (wild thyme) is a perennial shrub, native to areas of northern and central Europe. Its aerial parts are most frequently used in ethnomedicine (mainly for treating illnesses and problems related to the respiratory and gastrointestinal systems), although recently its essential oils are becoming more popular as an important plant-derived product. The composition of these oils is affected by geographic region, the development stage of the plant, the harvest season, habitat, and climatic conditions. Wild thyme essential oil has an ever-growing number of uses in contemporary medicine due to its pharmacological properties: antioxidative, antimicrobial, and anticancerogenic activities. The antioxidative and antimicrobial properties of the essential oil are related to the synergistic and cumulative effect of its components. In terms of antitumor and cytotoxic activity, further research into the effects of essential oil is necessary, aimed at improving its cytotoxic effects, on the basis of which appropriate medicines can be formulated. Due to its pharmacological properties, the essential oil of wild thyme, a plant used in traditional medicine, represents an important natural resource for the pharmaceutical industry. In addition, it can be a source of natural antioxidants, nutritional supplements, or components of functional foods in the food industry.


Serotonergic neurotransmission in the living human brain: a positron emission tomography study using [¹¹C]dasb and [¹¹C]WAY100635 in young healthy men.
The central serotonergic (5-HT) system is closely involved in regulating various mental functions such as mood and emotion. In this system, the serotonin transporter (5-HTT) and the 5-HT(1A) receptor play important roles in the pathophysiology and treatment of mood and anxiety disorders. However, only a few integrated databases have considered the intraindividual relationship between pre- and postsynaptic serotonergic transmission. In the present study, we constructed a database of 5-HTT and 5-HT(1A) receptors using positron emission tomography (PET) with [¹¹C]DASB and [¹¹C]WAY100635, respectively. Seventeen healthy young men participated in this study. After anatomic standardization of original images, BP(ND) was calculated on a voxel-by-voxel basis using reference tissue methods. The highest binding to 5-HTT was observed in the dorsal raphe nucleus, striatum, and thalamus; moderate binding, in the insula and cingulate cortex; and very low binding, in the cerebral neocortex. In contrast, the highest binding to 5-HT(1A) receptors was seen in the hippocampal regions, insula, neocortical regions, and dorsal raphe nucleus, and very low binding was found in the thalamus and basal ganglia. These distribution patterns were in agreement with those reported in human postmortem studies and previous PET investigations. In addition, exploratory analysis indicated significant negative correlations between the BP(ND) values with both radiotracers in certain regions of the brain, such as the cingulate, insula, and frontal, temporal and parietal cortices (Pearson's correlation, P < 0.05). These databases facilitate the understanding of the regional distribution of serotonergic neurotransmission function in the living human brain and the pathophysiology of various neuropsychiatric disorders.


Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101.
Histone acetylation has a central role in the control of gene expression, influencing transcriptional control of many genes, including tumor suppressor genes. PXD101 is a novel hydroxamate-type inhibitor of histone deacetylase activity that inhibits histone deacetylase activity in HeLa cell extracts with an IC(50) of 27 nM and induces a concentration-dependent (0.2-5 micro M) increase in acetylation of histone H4 in tumor cell lines. PXD101 is cytotoxic in vitro in a number of tumor cell lines with IC(50)s in the range 0.2-3.4 micro M as determined by a clonogenic assay and induces apoptosis. Treatment of nude mice bearing human ovarian and colon tumor xenografts with PXD101 (10-40 mg/kg/day i.p.) daily for 7 days causes a significant dose-dependent growth delay with no obvious signs of toxicity to the mice. Growth delay is also observed for xenografts of cisplatin-resistant ovarian tumor cells. A marked increase in acetylation of H4 is detected in blood and tumor of mice 3 h after treatment with PXD101. The inhibition of growth of human tumor xenografts in mice, with no apparent toxicity, suggests that PXD101 has potential as a novel antitumor agent. Furthermore, the ability to measure histone acetylation in blood samples could provide a suitable pharmacodynamic end point to monitor drug activity.


Induction of serum stimulation and plasma cell proliferation during chemotherapy of multiple myeloma.
Sequential sera from 45 patients with multiple myeloma (MM) and from 6 patients with solid tumors but normal bone marrows who received cyclophosphamide, 15 mg/kg/day for 4 days, were assayed for their effects on tritiated thymidine (3H-TdR) incorporation by normal bone marrow cells and malignant plasma cells. Pretreatment sera from 23 of the 45 patients with MM inhibited normal marrow cell proliferation relative to the effects of normal sera. Of these 45 sera, 30 inhibited plasma cell proliferation. This humoral inhibition was overcome by the induction of humoral stimulation at a predictable time during chemotherapy. The sera obtained sequentially from patients with MM and patients with normal bone marrows increased 3H-TdR uptake by both cell types by days 12-15 of therapy. Sequential changes in malignant marrow plasma cell 3H-TdR labeling indices paralleled the changes in serum activity, with an increased tumor cell growth fraction occurring at the time of peak serum stimulatory activity. The relationship between serum stimulation and malignant plasma cell proliferation was confirmed in vitro.


Eating buckwheat cookies is associated with the reduction in serum levels of myeloperoxidase and cholesterol: a double blind crossover study in day-care centre staffs.
Buckwheat food is a good source of antioxidants, e.g. rutin, and other beneficial substances. Here we investigated the effects of the intake of common buckwheat (low rutin content) and tartary buckwheat cookies (high rutin content) on selected clinical markers. A double blind crossover study was performed among female day-care centre staffs (N = 62) from five day-care centres. Participants were randomly divided into two groups. The first group initially consumed four common buckwheat cookies per day (16.5 mg rutin equivalents/day) for two weeks, while the second group consumed four tartary buckwheat cookies per day (359.7 mg rutin equivalents/day). Then the groups switched their type of cookies and consumed them for another two weeks. We monitored selected clinical markers related to cardiovascular disease and lower airway inflammation, lung function, and subjective breathing difficulties in the staffs. Intake of tartary buckwheat cookies reduced the serum level of myeloperoxidase (MPO) by a factor 0.84 (p = 0.02). When grouping the two types of buckwheat cookies together, there was a reduction of total serum cholesterol (p < 0.001) and HDL-cholesterol (p < 0.001) during the study period, with improved lung vital capacity (p < 0.001). The degree of reduction in total and HDL cholesterol levels was similar in staffs with low and high body mass index (cut off 25). In conclusion, intake of tartary buckwheat cookies with high level of the antioxidant rutin may reduce levels of MPO, an indicator of inflammation. Moreover, intake of both types of buckwheat cookies may lower cholesterol levels.


Interaction between serum levels of Anti-Mullerian Hormone and the degree of sperm DNA fragmentation measured by sperm chromatin structure assay can be a predictor for the outcome of standard in vitro fertilization.
Serum levels of Anti-Mullerian Hormone (AMH) have been shown to be biomarker for prediction of the quantitative aspects of ovarian reserve. On the male side, sperm chromatin structure assay (SCSA) DNA fragmentation index (DFI) has been demonstrated to be an important predictor of outcomes in standard IVF procedures but to less degree in intracytoplasmic sperm injection procedures (ICSI). The purpose of this study was to investigate whether the combination of female AMH serum levels and sperm DFI adds to prediction of the outcome of assisted reproduction. A total of 352 couples was included (ICSI-148: IVF-204) A venous blood sample was drawn for AMH analysis before IVF/ICSI treatment. DFI was measured in the ejaculate used for assisted reproduction. Regression models for the following odds ratio calculations were constructed: for obtaining at least one Good Quality Embryo; for live birth in all procedures; for pregnancy in procedures where embryo transfer was performed; for miscarriage. For DFI increase by 10 percentage points (not increased DFI as reference) odds ratio for Good Quality Embryo was statistically significantly lower when AMH was at lower quartile (AMH <12 pmol/L; OR = 0.29, 95% CI: 0.14-0.59,) but not when AMH was at upper quartile (AMH ≥ 36 pmol/L; OR = 0.95, 95% CI: 0.43-2.13,). The marginal effect of an increase in DFI by 10 percentage points was statistically significant only when AMH < 25.2 pmol/L. Similar results were obtained as considers live birth following standard IVF. No interactions were seen for standard IVF in relation to the risk of miscarriage and for any of the outcomes when ICSI was used as method of treatment. We conclude that the impact of high DFI on the outcome of standard IVF is most pronounced if the female partner has relatively low AMH levels. This finding may help in defining the role of sperm DNA integrity testing in management of infertile couples. It may also explain some of the heterogeneity in results of studies focusing on predictive value of DFI measurements in assisted reproduction.


Results of a randomized feasibility study of a low-fat diet.
A 2-year randomized clinical trial was conducted to test whether free-living women aged 45 to 69 years can reduce the fat content of their diet from the typical US level of approximately 39% to 20% of energy from fat, using readily available foods, when given nutritional and behavioral counseling and social support. Three clinical units randomized 303 selected volunteers into intervention (low-fat eating plan) or control (customary diet) groups. The two groups were comparable at baseline. The intervention group received nutrition instruction and behavioral counseling largely in permanent groups of 12 to 15 participants meeting weekly, then biweekly, and finally monthly. At 6 months, they had substantially reduced the mean proportion of total energy from fat from 39.1% to 20.9%, compared with the control group's nonsignificant reduction from 39.0% to 38.1%. At 12 and 24 months, they sustained the reduction of energy from fat. Weight loss and plasma cholesterol level changes in the intervention group supported the self-recorded dietary intake changes. Attendance at intervention sessions averaged 75% during the first 6 months and, subsequently, 60% to 70%. Four-day food records for the randomized women were obtained at 6 and 12 months from approximately 95% and at 24 months from 87%. A clinical trial of a low-fat diet is feasible in women.


HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation.
APOBEC3 (A3) family proteins are DNA cytosine deaminases recognized for contributing to HIV-1 restriction and mutation. Prior studies have demonstrated that A3D, A3F, and A3G enzymes elicit a robust anti-HIV-1 effect in cell cultures and in humanized mouse models. Human A3H is polymorphic and can be categorized into three phenotypes: stable, intermediate, and unstable. However, the anti-viral effect of endogenous A3H in vivo has yet to be examined. Here we utilize a hematopoietic stem cell-transplanted humanized mouse model and demonstrate that stable A3H robustly affects HIV-1 fitness in vivo. In contrast, the selection pressure mediated by intermediate A3H is relaxed. Intriguingly, viral genomic RNA sequencing reveled that HIV-1 frequently adapts to better counteract stable A3H during replication in humanized mice. Molecular phylogenetic analyses and mathematical modeling suggest that stable A3H may be a critical factor in human-to-human viral transmission. Taken together, this study provides evidence that stable variants of A3H impose selective pressure on HIV-1.


Colonization of Abiotic Surfaces.
E. coli is a relevant model organism for the study of the molecular mechanisms underlying surface colonization. This process requires two essential steps: adhesion to a surface, followed by cell-cell adhesion counteracting the shear forces of the environment, with both steps contributing to the formation of a biofilm. This review provides an overview of the current knowledge of the genetic analyses aiming at identifying factors involved in both of these two highly related biological processes, with a particular emphasis on studies performed in Escherichia coli K-12. Bacterial adhesion to abiotic surfaces is likely to be highly dependent on the physicochemical and electrostatic interactions between the bacterial envelope and the substrate, which is itself often conditioned by the fluids to which it is exposed. Genetic analyses have revealed the diversity of genetic factors in E. coli that participate in colonization and biofilm formation on abiotic surfaces. The study of surface colonization and biofilm formation represents a rapidly expanding field of investigation. The use of E. coli K-12 to investigate the genetic basis of bacterial interactions with surfaces has led to the identification of a large repertoire of adhesins whose expression is subject to a complex interplay between regulatory networks. Understanding how E. coli K-12 behaves in complex biofilm communities will certainly contribute to an understanding of how natural commensal and pathogenic E. coli isolates develop.


Are plant formins integral membrane proteins?
The formin family of proteins has been implicated in signaling pathways of cellular morphogenesis in both animals and fungi; in the latter case, at least, they participate in communication between the actin cytoskeleton and the cell surface. Nevertheless, they appear to be cytoplasmic or nuclear proteins, and it is not clear whether they communicate with the plasma membrane, and if so, how. Because nothing is known about formin function in plants, I performed a systematic search for putative Arabidopsis thaliana formin homologs. I found eight putative formin-coding genes in the publicly available part of the Arabidopsis genome sequence and analyzed their predicted protein sequences. Surprisingly, some of them lack parts of the conserved formin-homology 2 (FH2) domain and the majority of them seem to have signal sequences and putative transmembrane segments that are not found in yeast or animals formins. Plant formins define a distinct subfamily. The presence in most Arabidopsis formins of sequence motifs typical or transmembrane proteins suggests a mechanism of membrane attachment that may be specific to plant formins, and indicates an unexpected evolutionary flexibility of the conserved formin domain.


The HCPro from the Potyviridae family: an enviable multitasking Helper Component that every virus would like to have.
RNA viruses have very compact genomes and so provide a unique opportunity to study how evolution works to optimize the use of very limited genomic information. A widespread viral strategy to solve this issue concerning the coding space relies on the expression of proteins with multiple functions. Members of the family Potyviridae, the most abundant group of RNA viruses in plants, offer several attractive examples of viral factors which play roles in diverse infection-related pathways. The Helper Component Proteinase (HCPro) is an essential and well-characterized multitasking protein for which at least three independent functions have been described: (i) viral plant-to-plant transmission; (ii) polyprotein maturation; and (iii) RNA silencing suppression. Moreover, multitudes of host factors have been found to interact with HCPro. Intriguingly, most of these partners have not been ascribed to any of the HCPro roles during the infectious cycle, supporting the idea that this protein might play even more roles than those already established. In this comprehensive review, we attempt to summarize our current knowledge about HCPro and its already attributed and putative novel roles, and to discuss the similarities and differences regarding this factor in members of this important viral family.


Effect of tomato juice consumption on the plasmatic lipid profile, hepatic HMGCR activity, and fecal short chain fatty acid content of rats.
The aims of the present study were to ascertain, indirectly, the prebiotic role of tomato juice, by analyzing its effect on the content of short chain fatty acids (SCFA) in feces of rats, and to determine the plausible mechanisms related to the hypocholesterolemic effects of tomato juice and lycopene, evaluating the activity of hepatic HMGCR and the formation of propionic acid. Two commercially available tomato juices with differing contents of lycopene (low and high lycopene contents: Llyc and Hlyc tomato juices) were used. Sprague-Dawley male rats were randomly divided into three experimental groups (n = 8): control group, normal diet and water; group 1, normal diet and Llyc tomato juice; and group 2, normal diet and Hlyc tomato juice, which were fed ad libitum for three weeks. Feces were collected at the beginning and the end of the study to determine SCFA, and blood and liver were obtained (after sacrificing the animals) to analyze the lipid plasmatic parameters and the HMGCR activity and total cholesterol, respectively. No significant differences were observed in the plasmatic parameters, except that HDL-cholesterol increased significantly after consumption of both tomato juices. Lycopene was accumulated in the liver in proportion to the amount ingested, and was observed to have an inhibitory effect on the HMGCR enzyme, according to the amount of lycopene in the liver. In relation to the SCFA in feces, no differences were observed in acetate and propionate after the consumption of tomato juice, but a significant increase in butyrate was observed in group 2 after the intake of Hlyc tomato juice. The content of this carboxylic acid together with excreted lycopene in feces could have a beneficial effect on colonic cells.


Cryptomeria japonica essential oil inhibits the growth of drug-resistant skin pathogens and LPS-induced nitric oxide and pro-inflammatory cytokine production.
In this study, the chemical composition of Cryptomeria japonica essential oil (CJE) was analyzed and its biological activities were tested. CJE was obtained by steam distillation from leaves collected from Jeju Island and analyzed by gas chromatography (GC)-flame ionization detection (FID) and GC-MS. Kaurene (17.20%), elemol (10.88%), gamma-eudesmol (9.41%), and sabinene (8.86%) were the major components in CJE. The antibacterial and anti-inflammatory activities of CJE against drug-susceptible and -resistant skin pathogens have been not reported previously. Thus, we determined the anti-bacterial activities of CJE using the disk diffusion method and minimum inhibitory concentration (MIC) values. CJE showed excellent antibacterial activities against Propionibacterium acnes and Staphylococcus epidermidis, which are acne-causing bacteria. The MIC of CJE against drug-susceptible and -resistant P. acens and S. epidermidis ranged from 0.16 to 10.0 microl/ml. In addition, the effects of CJE on nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages were also examined. Pro-inflammatory cytokine and mediator tests indicated that CJE has excellent dose-dependent inhibitory activities. Therefore, based on these results, we propose that CJE is an attractive acne-mitigating candidate for skin health.


Guidelines for psychosocial interventions in dementia care: a European survey and comparison.
The effectiveness of psychosocial interventions in treating people with dementia and their carers is increasingly emphasised in the literature. Dementia guidelines should summarise the scientific evidence and best practice that is currently available, therefore, it should include recommendations for psychosocial interventions. The aims of our study were (1) to collate dementia guidelines from countries across Europe and to check whether they included sections about psychosocial interventions, and (2) to compare the methodological quality and the recommendations for specific psychosocial interventions in these guidelines. The European dementia guidelines were inventoried. The methodological quality of the guideline sections for psychosocial interventions was assessed with the (AGREE) Appraisal of Guidelines Research and Evaluation instrument. The recommendations for specific psychosocial interventions were extracted from each of these guidelines and compared. Guidelines for psychosocial interventions were found in five of 12 countries. Guideline developers, methodological quality and appreciation of available evidence influenced the inclusion of psychosocial interventions in dementia guidelines from Germany, Italy, the Netherlands, Spain and the UK. The UK NICE SCIE guideline had the best methodological quality and included the most recommendations for psychosocial interventions. Physical activity and carer interventions were recommended the most across all guidelines. The inclusion of psychosocial interventions in dementia guidelines is limited across Europe. High-quality guidelines that include psychosocial interventions and are kept up to date with the emerging evidence are needed. Throughout Europe, special attention to the implementation of evidence-based psychosocial care is needed in the next few years.


Acoustic cavitation as an enhancing mechanism of low-frequency sonophoresis for transdermal drug delivery.
We investigated the role of acoustic cavitation on sonophoretic skin permeation of calcein, a model permeant, across excised hairless rat skin. Three different frequencies (41, 158, 445 kHz) and various intensities (60 to 300 mW/cm(2)) of ultrasound were applied. Cavitation generation in degassed and undegassed (normal) water was monitored using a commercially available cavitation meter, then compared with skin permeability from calcein solution consistent of them. In addition, the penetration of a fluorescent dye, rhodamine B, into gelatin gel as a skin alternative was observed to estimate the role of cavitation collapse in the solution at or near the skin surface. Cavitation generation in the undegassed water was dependent on the ultrasound frequency, and the rank order of the cavitation was 41 kHz>158 kHz>445 kHz. At 41 kHz, cavitation generation in degassed water was clearly lower than that in undegassed water. Calcein permeability during ultrasound application correlated well with the cavitation generation in the medium, suggesting the important role of the indirect actions of cavitation collapse which occurred in the applied solution rather than the direct action in the skin. When ultrasound (41 or 158 kHz) was applied to the gelatin gels covered with rhodamine B solution, alteration in the surface configuration, like spots, and the coincident penetration of the dye were observed only at 41 kHz, while no alteration in the surface configuration was evident at 158 kHz. These results suggest that cavitation collapses in the vicinity of the skin surface might be more important for solute penetration in addition to skin permeabilization.


CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells.
While interactions between CD28 and members of the B7 family costimulate and enhance T cell responses, recent evidence indicates that the CD28 homologue CTLA-4 plays a downregulatory role. The mechanism by which this occurs is not clear, but it has been suggested that CTLA-4 terminates ongoing responses of activated T cells, perhaps by induction of apoptosis. Here we demonstrate that CTLA-4 engagement by antibody cross-linking or binding to B7 inhibits proliferation and accumulation of the primary T cell growth factor, IL-2, by cells stimulated with anti-CD3 and anti-CD28. This inhibition is not a result of enhanced cell death. Rather it appears to result from restriction of transition from the G1 to the S phase of the cell cycle. Our observation that upregulation of both the IL-2R alpha chain and the CD69 activation antigen are inhibited by CTLA-4 engagement supplies further evidence that CTLA-4 restricts the progression of T cells to an activated state. Together this data demonstrates that CTLA-4 can regulate T cell activation in the absence of induction of apoptotic cell death.


Alcoholism in the general hospital.
To assess the prevalence of alcoholism among people admitted to hospital 303 patients completed a drinking questionnaire. A total of 59 (19.5%) were found to have a drinking problem, which constituted a sixfold greater prevalence than recorded in a community survey using the same technique. The drinkers were mostly men and tended to be younger than the non-drinkers and to smoke more heavily, live in more crowded conditions, and be of lower social class. Significantly more of the drinkers had at least one parent who was an alcoholic. The results confirm that hospital inpatients comprise a larger proportion of alcoholics than found in the general population. Hence medical staff should be alert to such patients, so that treatment may be initiated at an early stage of social decompensation.


Risk management in clinical practice. Part 4. Endodontics.
Endodontic procedures are challenging and technically demanding. In the UK standards of treatment have been shown to have fallen short of acceptable guidelines, laying many dentists open to litigation on questions of clinical negligence by patients who understand and know what should be considered as current best practice in this area. Failure to communicate with patients about the procedure and not obtaining consent for treatment is a key area of complaint, as is inadequate record keeping. When treatment is undertaken within the framework of accepted guidelines it would be very difficult for a patient to open a claim for clinical negligence should a failure occur. This article looks at potential dento-legal problems in endodontics and how, through compliance with best practice, they may be avoided.