The Single Distinct Leader Protease Encoded by Alpinia oxyphylla Mosaic Virus (Genus Macluravirus) Suppresses RNA Silencing Through Interfering with Double-Stranded RNA Synthesis.
The genomic 5'-terminal regions of viruses in the family Potyviridae (potyvirids) encode two types of leader proteases: serine-protease (P1) and cysteine-protease (HCPro), which differ greatly in the arrangement and sequence composition among inter-genus viruses. Most potyvirids have the same tandemly arranged P1 and HCPro, whereas viruses in the genus Macluravirus encode a single distinct leader protease, a truncated version of HCPro with yet-unknown functions. We investigated the RNA silencing suppression (RSS) activity and its underpinning mechanism of the distinct HCPro from alpinia oxyphylla mosaic macluravirus (aHCPro). Sequence analysis revealed that macluraviral HCPros have obvious truncations in the N-terminal and middle regions when aligned to their counterparts in potyviruses (well-characterized viral suppressors of RNA silencing). Nearly all defined elements essential for the RSS activity of potyviral counterparts are not distinguished in macluraviral HCPros. Here, we demonstrated that aHCPro exhibits a similar anti-silencing activity with the potyviral counterpart. However, aHCPro fails to block both the local and systemic spreading of RNA silencing. In line, aHCPro interferes with the dsRNA synthesis, an upstream step in the RNA silencing pathway. Affinity-purification and NanoLC-MS/MS analysis revealed that aHCPro has no association with core components or their potential interactors involving in dsRNA synthesis from the protein layer. Instead, the ectopic expression of aHCPro significantly reduces the transcript abundance of RDR2, RDR6, SGS3, and SDE5. This study represents the first report on the anti-silencing function of Macluravirus-encoded HCPro and the underlying molecular mechanism.


Identification of glutathione (GSH)-independent glyoxalase III from Schizosaccharomyces pombe.
Reactive carbonyl species (RCS), such as methylglyoxal (MG) and glyoxal (GO), are synthesized as toxic metabolites in living systems. Mechanisms of RCS detoxification include the glutathione (GSH)-dependent system consisting of glyoxalase I (GLO1) and glyoxalase II (GLO2), and GSH-independent system involving glyoxalase III (GLO3). Hsp31 and DJ-1 proteins are weakly homologous to each other and belong to two different subfamilies of the DJ-1/Hsp31/PfpI superfamily. Recently, the Escherichia coli Hsp31 protein and the DJ-1 proteins from Arabidopsis thaliana and metazoans have been demonstrated to have GLO3 activity. We performed a systematic survey of homologs of DJ-1 and Hsp31 in fungi. We found that DJ-1 proteins have a very limited distribution in fungi, whereas Hsp31 proteins are widely distributed among different fungal groups. Phylogenetic analysis revealed that fungal and metazoan DJ-1 proteins and bacterial YajL proteins are most closely related and together form a sister clade to bacterial and fungal Hsp31 proteins. We showed that two Schizosaccharomyces pombe Hsp31 proteins (Hsp3101 and Hsp3102) and one Saccharomyces cerevisiae Hsp31 protein (ScHsp31) displayed significantly higher in vitro GLO3 activity than S. pombe DJ-1 (SpDJ-1). Overexpression of hsp3101, hsp3102 and ScHSP31 could confer MG and GO resistance on either wild-type S. pombe cells or GLO1 deletion of S. pombe. S. pombe DJ-1 and Hsp31 proteins exhibit different patterns of subcellular localization. Our results suggest that fungal Hsp31 proteins are the major GLO3 that may have some role in protecting cells from RCS toxicity in fungi. Our results also support the view that the GLO3 activity of Hsp31 proteins may have evolved independently from that of DJ-1 proteins.


Infectious cDNA clone of the RA27/3 vaccine strain of Rubella virus.
Rubella virus (RUB), a small plus-strand RNA virus, is a significant human pathogen. The RA27/3 vaccine strain of RUB is one of the most successful live attenuated vaccines developed. In this article, we report the construction of an RA27/3 infectious clone, a complete cDNA copy of the RA27/3 genome that can be transcribed in vitro to generate infectious RNA molecules. Virus generated from such in vitro transcripts was phenotypically similar to RA27/3 virus. To investigate the attenuation of the RA27/3 strain, a series of chimeras was made by the insertion of different fragments of the RA27/3 genome into an infectious clone based on the Therien wild-type strain of RUB. Analysis of the resulting chimeric viruses revealed that the pattern of RA27/3 attenuation in cell culture is complex: attenuating elements in the RA27/3 genome were found in the 5' untranslated region (UTR), a region of the nonstructural proteins containing the protease motif and the capsid gene. Within the 5' UTR, the attenuation determinant was mapped to nt 7. Surprisingly, these analyses also revealed a potentiating mutation at nt 164 of the RA27/3 genome. Although this determinant was within the coding sequences of the nonstructural proteins, the encoded amino acid had no effect on cell culture phenotype and thus the determinant may operate at the level of RNA structure. In addition to investigation of the mechanisms of RA27/3 attenuation, the availability of the RA27/3 infectious clone offers the opportunity for strict genetic control over RUB vaccine manufacturing, for development of novel DNA-based vaccines against RUB, and for development of recombinant RUB vaccines that also target other diseases.


A new method for data stream mining based on the misclassification error.
In this paper, a new method for constructing decision trees for stream data is proposed. First a new splitting criterion based on the misclassification error is derived. A theorem is proven showing that the best attribute computed in considered node according to the available data sample is the same, with some high probability, as the attribute derived from the whole infinite data stream. Next this result is combined with the splitting criterion based on the Gini index. It is shown that such combination provides the highest accuracy among all studied algorithms.


Alefacept-induced decreases in circulating blood lymphocyte counts correlate with clinical response in patients with chronic plaque psoriasis.
This international, double-blind study examined the effects of alefacept on circulating lymphocytes in 507 patients with chronic plaque psoriasis, and determined whether these effects were related to clinical improvement. Patients were randomized to intramuscular placebo, alefacept 10 mg, or alefacept 15 mg once weekly for 12 weeks followed by 12 weeks of observation. Alefacept dose-dependently reduced CD4+ and CD8+ memory T cells, while sparing the na ve population. The greatest reductions in disease activity occurred in patients with the largest decreases in memory T cells. For example, a 50 % reduction from baseline Psoriasis Area Severity Index at any time during treatment or follow-up was observed in 66 % of patients who had the greatest reductions in CD4+ memory T cells versus in 40 % of patients who had the smallest reductions in this T-cell subset. These results provide further support for the deleterious roles of CD4+ and CD8+ memory T-cell subpopulations in psoriasis pathogenesis.


A medical paradox: curative versus preventive medicine.
A familiar medical contrast is presented as part of a modern medical problem. The problem it reflects is the relative importance of preventive and curative services for medical practitioners, which is already, or will shortly resolve itself into, a dilemma of whether medical men should stress preventive medicine to the possible detriment of curative medicine. It is submitted that the solution to both problem and dilemma should be sought against the background of history and philosophy, where they are seen to be expressions of an eternal paradox--that of the relative value of the individual in relation to the family, group, or community. If the submission is valid, then the answer to the problem is not a purely medical exercise, nor is the dilemma purely a 'doctor's dilemma'. The paradox, being eternal, is not soluble in our time, but the community must, on the urging of the medical profession, find a general solution to the problem--'a public consensus for out time'. This must be followed by public demand for a parliamentary solution--'decision-making ex consensus'. It is argued that although the latter programme does not come easily to democracy, it can be achieved through public consensus if action is taken by the leaders of thought in appropriate categories. Initiative must be exercised by the medical profession, but public consensus can only be achieved in consultation with the leaders of all learned professions, civil servants and legislators. It must then be presented fairly and without bias to the public. In the meantime, the medical profession must formulate its own 'medical consensus' and the doctor must resolve his personal dilemma according to formulated law, public or medical consensus or, in the last resort, according to his conviction and conscience. This method of solving a problem will almost certainly be applicable to other and more recent medical problems such as the population explosion, selective abortion and euthanasia.


Molecular and serological evidence for the presence of novel phleboviruses in sandflies from northern algeria.
During summer 2007, a total of 785 phlebotomine flies were trapped in northern Algeria, identified morphologically, organised as monospecific pools and tested for the presence of phlebovirus RNA using degenerate primers. Three pools were positive, and the corresponding PCR products were cloned and sequenced. Viral sequences corresponding to two phleboviruses distinct from each other were detected in sandflies circulating in two close locations (140 km apart) in Northern Algeria. The 3 sequences were aligned with homologous polymerase sequences retrieved from the Genbank database, in order to examine their phylogenetic relationships. One viral sequence (from Phlebotomus papatasi) was closely related to but distinct from a sequence obtained from Phlebotomus ariasi sandflies trapped in Algeria in 2006. The two other viral sequences (from Phlebotomus longicuspis) were genetically distantly related to sequences corresponding to virus members of the Sandfly fever Naples virus species and although falling within the same group, this clearly represents a second distinct novel lineage. These results are indicative of a high genetic heterogeneity within sandflies trapped in a relatively small geographic area. Seroprevalence studies conducted on sera from populations living in the same areas indicated that humans can be infected by these viruses.


Effect of sunlight on survival of indicator bacteria in seawater.
The stability of the natural populations of fecal coliforms and fecal streptococci in raw sewage diluted 1:1,000 in seawater or phosphate-buffered water at 24 +/- 2 degrees C was markedly affected by the absence or presence of sunlight. In the absence of sunlight, these bacteria survived for days, whereas in the presence of sunlight 90% of the fecal coliforms and fecal streptococci were inactivated within 30 to 90 min and 60 to 180 min, respectively. The bactericidal effect of sunlight was shown to penetrate glass, translucent polyethylene, and at least 3.3 m of clear seawater, suggesting that the visible rather than the ultraviolet light spectrum of sunlight was primarily responsible for the observed bactericidal effect. However, these same sewage-borne bacteria were relatively resistant to the bactericidal effect of sunlight when diluted in fresh mountain stream waters. These results indicate that the presence of sunlight is a major factor controlling the survival of fecal coliforms and fecal streptococci in seawater.


Compartmentalization of Ras proteins.
The Ras GTPases operate as molecular switches that link extracellular stimuli with a diverse range of biological outcomes. Although many studies have concentrated on the protein-protein interactions within the complex signaling cascades regulated by Ras, it is becoming clear that the spatial orientation of different Ras isoforms within the plasma membrane is also critical for their function. H-Ras, N-Ras and K-Ras use different membrane anchors to attach to the plasma membrane. Recently it has been shown that these anchors also act as trafficking signals that direct palmitoylated H-Ras and N-Ras through the exocytic pathway to the cell surface but divert polybasic K-Ras around the Golgi to the plasma membrane via an as yet-unidentified-route. Once at the plasma membrane, H-Ras and K-Ras operate in different microdomains. K-Ras is localized predominantly to the disordered plasma membrane, whereas H-Ras exists in a GTP-regulated equilibrium between disordered plasma membrane and cholesterol-rich lipid rafts. These observations provide a likely explanation for the increasing number of biological differences being identified between the otherwise highly homologous Ras isoforms and raise interesting questions about the role membrane microlocalization plays in determining the interactions of Ras with its effectors and exchange factors.


Temperature and the Ventilatory Response to Hypoxia in Gromphadorhina portentosa (Blattodea: Blaberidae).
In general, insects respond to hypoxia by increasing ventilation frequency, as seen in most other animals. Higher body temperatures usually also increase ventilation rates, likely due to increases in metabolic rates. In ectothermic air-breathing vertebrates, body temperatures and hypoxia tend to interact significantly, with an increasing responsiveness of ventilation to hypoxia at higher temperatures. Here, we tested whether the same is true in insects, using the Madagascar hissing cockroach, Gromphadorhina portentosa (Schaum) (Blattodea: Blaberidae). We equilibrated individuals to a temperature (beginning at 20 °C), and animals were exposed to step-wise decreases in PO2 (21, 15, 10, and 5 kPa, in that order), and we measured ventilation frequencies from videotapes of abdominal pumping after 15 min of exposure to the test oxygen level. We then raised the temperature by 5 °C, and the protocol was repeated, with tests run at 20, 25, 30, and 35 °C. The 20 °C animals had high initial ventilation rates, possibly due to handling stress, so these animals were excluded from subsequent analyses. Across all temperatures, ventilation increased in hypoxia, but only significantly at 5 kPa PO2 Surprisingly, there was no significant interaction between temperature and oxygen, and no significant effect of temperature on ventilation frequency from 25 to 35 °C. Plausibly, the rise in metabolic rates at higher temperatures in insects is made possible by increasing other aspects of gas exchange, such as decreasing internal PO2, or increases in tidal volume, spiracular opening (duration or amount), or removal of fluid from the tracheoles.


Magnetically recoverable catalysts for the preparation of pyridine derivatives: an overview.
Magnetically recoverable nano-catalysts can be readily separated from the reaction medium using an external magnet. In recent years, chemistry researchers have employed them as catalysts in chemical reactions. The high surface area, simple preparation, and modification are among their major advantages. Pyridine derivatives are an important category of heterocyclic compounds, which show a wide range of excellent biological activities, including IKK-β inhibitors, anti-microbial agents, A2A adenosine receptor antagonists, inhibitors of HIV-1 integrase, anti-tumor, anti-inflammatory, and anti-Parkinsonism. Recently, the catalytic activity of magnetic nanoparticles was investigated in multicomponent reactions in the synthesis of pyridine derivatives, which is discussed in this review.


TP003 is a non-selective benzodiazepine site agonist that induces anxiolysis via α2GABAA receptors.
Benzodiazepines (BDZ), which potentiate the action of GABA at four subtypes of GABAA receptors (α1, α2, α3, and α5GABAARs), are highly effective against anxiety disorders, but also cause severe side effects greatly limiting their clinical application. Both, preclinical studies in genetically engineered mice, and preclinical and clinical trials with subtype-selective compounds indicate that undesired effects can in principle be avoided by targeting specific GABAAR subtypes. While there is general consensus that activity at α1GABAARs should be avoided, controversy exists as to whether α2 or α3GABAARs need to be targeted for anxiolysis. While previous experiments in GABAAR point-mutated mice demonstrated a critical role of α2GABAARs, studies solely relying on pharmacological approaches suggested a dominant contribution of α3GABAARs. As most α1GABAAR-sparing BDZ site agonists discriminate little between α2 and α3GABAARs, these claims rest almost exclusively on a single compound, TP003, that has been reported to be a selective α3GABAAR modulator. Here, we have revisited the in vitro pharmacological profile of TP003 and, in addition, tested TP003 in GABAAR triple point-mutated mice, in which only either α1, α2, or α3GABAARs were left BDZ sensitive. These experiments revealed that TP003 behaves as a partial, rather non-selective BDZ site agonist in vitro that acts in vivo through α1, α2, and α3GABAARs (α5GABAAR-mediated effects were not tested). With respect to anxiolysis, our results support a critical contribution of α2GABAARs, but not of α3GABAARs. TP003 should therefore not be considered an α3GABAAR selective agent. Previously published studies using TP003 should be interpreted with caution.


Characterization of a membrane-associated serine protease in Escherichia coli.
Three membrane-associated proteolytic activities in Escherichia coli were resolved by DEAE-cellulose chromatography from detergent extracts of the total envelope fraction. On the basis of substrate specificity for the hydrolysis of chromogenic amino acid ester substrates, the first two eluting activities were determined previously to be protease V and protease IV, respectively (M. Pacaud, J. Bacteriol. 149:6-14, 1982). The third proteolytic activity eluting from the DEAE-cellulose column was further purified by affinity chromatography on benzamidine-Sepharose 6B. We termed this enzyme protease VI. Protease VI did not hydrolyze any of the chromogenic substrates used in the detection of protease IV and protease V. However, all three enzymes generated acid-soluble fragments from a mixture of E. coli membrane proteins which were biosynthetically labeled with radioactive amino acids. The activity of protease VI was sensitive to serine protease inhibitors. Using [3H]diisopropylfluorophosphate as an active-site labeling reagent, we determined that protease VI has an apparent molecular weight of 43,000 in polyacrylamide gels. All three membrane-associated serine proteases were insensitive to inhibition by Ecotin, and endogenous, periplasmic inhibitor of trypsin.


Genomic analysis of the 55 kDa subunit of DNA polymerase epsilon in human intracranial neoplasms.
Defects of some DNA polymerases have shown cancer associations, but there are only limited data on DNA polymerase (Pol) epsilon. We examined 26 human brain neoplasm DNA samples and 8 control blood samples (from Poland) for possible mutations in the entire coding region of the 55 kDa small subunit of human DNA Pol epsilon gene using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis, and sequence analysis of DNA. One single base intronic transition in intron 14 was found. The AATT deletion previously found in some breast and colorectal tumors was not found in samples from brain neoplasms or controls, but it was found in 1/100 normal blood samples from South-West Finland. We found no evidence that potential mutations in the 55 kDa subunit of DNA Pol epsilon are a contributing factor in the development of the tested cases of human intracranial tumors.


Using the Community Multiscale Air Quality (CMAQ) model to estimate public health impacts of PM2.5 from individual power plants.
We estimated PM2.5-related public health impacts/ton emitted of primary PM2.5, SO2, and NOx for a set of power plants in the Mid-Atlantic and Lower Great Lakes regions of the United States, selected to include varying emission profiles and broad geographic representation. We then developed a regression model explaining variability in impacts per ton emitted using the population distributions around each plant. We linked outputs from the Community Multiscale Air Quality (CMAQ) model v 4.7.1 with census data and concentration-response functions for PM2.5-related mortality, and monetized health estimates using the value-of-statistical-life. The median impacts for the final set of plants were $130,000/ton for primary PM2.5 (range: $22,000-230,000), $28,000/ton for SO2 (range: $19,000-33,000), and $16,000/ton for NOx (range: $7100-26,000). Impacts of NOx were a median of 34% (range: 20%-75%) from ammonium nitrate and 66% (range: 25%-79%) from ammonium sulfate. The latter pathway is likely from NOx enhancing atmospheric oxidative capacity and amplifying sulfate formation, and is often excluded. Our regression models explained most of the variation in impact/ton estimates using basic population covariates, and can aid in estimating impacts averted from interventions such as pollution controls, alternative energy installations, or demand-side management.


Stress is associated with unfavorable patterns of dietary intake among female chinese immigrants.
Chinese immigrants experience increased risk for weight gain and chronic disease after US migration. Whether psychosocial stress affects their eating behavior is unknown. The purpose of this study is to examine psychosocial stress and dietary intake among 426 Chinese immigrant women in the Philadelphia region. Participants completed 4 days of dietary recalls and questionnaires assessing positive and negative life events in the past year and migration-related stressors. In hierarchical linear regression models, positive life events were associated with higher energy intake (β = 21.1, p = 0.04). Migration-related stress was associated with lower total gram (β = -11.3, p < 0.0001) and overall grain (β = -0.18, p = 0.03) intake and higher energy density (β = 0.002, p = 0.04) and percent energy from fat (β = 0.06, p = 0.05). Migration-related stress did not increase overall intake in terms of energy and total grams but selectively increased fat intake and energy density. Such dietary habits may have implications for future chronic disease risk in this immigrant population.


Internalization and endosomal degradation of receptor-bound antigens regulate the efficiency of cross presentation by human dendritic cells.
Dendritic cells (DCs) can capture extracellular antigens and load resultant peptides on to MHC class I molecules, a process termed cross presentation. The mechanisms of cross presentation remain incompletely understood, particularly in primary human DCs. One unknown is the extent to which antigen delivery to distinct endocytic compartments determines cross presentation efficiency, possibly by influencing antigen egress to the cytosol. We addressed the problem directly and quantitatively by comparing the cross presentation of identical antigens conjugated with antibodies against different DC receptors that are targeted to early or late endosomes at distinct efficiencies. In human BDCA1+ and monocyte-derived DCs, CD40 and mannose receptor targeted antibody conjugates to early endosomes, whereas DEC205 targeted antigen primarily to late compartments. Surprisingly, the receptor least efficient at internalization, CD40, was the most efficient at cross presentation. This did not reflect DC activation by CD40, but rather its relatively poor uptake or intra-endosomal degradation compared with mannose receptor or DEC205. Thus, although both early and late endosomes appear to support cross presentation in human DCs, internalization efficiency, especially to late compartments, may be a negative predictor of activity when selecting receptors for vaccine development.


Racial Differences in Patient-Reported Access to Telehealth: An Important and Unmeasured Social Determinant of Health.
The COVID-19 pandemic expanded opportunities for remote oncology telehealth visits. However, reliable internet connectivity, digital literacy, and patient comfort with virtual medical visits may differ among patients, especially socially disadvantaged groups. The primary aim of this study was to identify barriers that might limit access to telehealth video services. First, retrospective analysis was performed of composite administrative data of all patient visits to a large regional cancer center during the pandemic (March 2020 to April 2022). Second, a prospective, cross-sectional study was conducted of patients with known or suspected malignancy over a 6-month period (November 2021 to April 2022). A survey regarding video telehealth accessibility was verbally administered to patients at their clinic visit. Administrative data demonstrated that although Black patients comprised 43% (n = 9,021) of all patient visits (n = 20,953), the proportion of telehealth visits conducted among Black patients was significantly lower compared with White patients (29% v 71%; P < .0001). Of the prospective, cross-sectional study cohort (n = 148), 51.4% of patients (n = 76) were Black, 38.5% (n = 57) resided in a rural county, and 8.1% (n = 12) were Medicaid-insured. Black participants were more likely to self-report lack of internet access (73.7% v 90.4%; P < .01) and were less likely to report having access to or actively using a patient portal (29.0% v 47.2%; P < .001) compared with White patients. The independent association of race and internet access (P < .05) and patient portal use (P = .001) persisted after multivariable analysis. Black patients disproportionately underparticipated in telehealth visits, suggesting underlying structural disparities in access to digital care. A greater proportion of Black participants self-reported lack of internet access and access to a patient portal compared with White patients. Ensuring equal internet access and digital literacy will be critical to reduce disparities in cancer care among racial minorities.


Using Fatigue Characteristics to Analyse Test Results for 16Mo3 Steel under Tension-Compression and Oscillatory Bending Conditions.
In this study, 16Mo3 steel was analysed for fatigue tests under tension-compression and oscillatory bending conditions. The analysis involved a comparison of fatigue test results obtained using the Manson-Coffin-Basquin, Langer and Kandil models and the models proposed by Kurek-Łagoda. It was observed that it is possible to substitute the basic tension-compression test performed in large testing machines with oscillatory bending tests carried out on a simple, modern test stand. The tests were performed under oscillatory bending on a prototype machine. The testing of 16Mo3 steel proved that the best-known Mason-Coffin-Basquin fatigue characteristic describes the results of all of the experimental tests very well, but the model can only be used when it is possible to divide strains into elastic and plastic components. It should be emphasised here that there is no such possibility in the case of tests performed under oscillatory bending conditions. It was proven that the proposed test method can substitute the tension-compression test very well and be a much more cost efficient way to obtain LCF material fatigue properties.


Polyunsaturated Fat Intake Estimated by Circulating Biomarkers and Risk of Cardiovascular Disease and All-Cause Mortality in a Population-Based Cohort of 60-Year-Old Men and Women.
High intake of polyunsaturated fatty acids (PUFAs) may reduce the risk of cardiovascular disease (CVD) and mortality. Large, prospective studies including both sexes and circulating PUFAs as dietary biomarkers are needed. We investigated sex-specific associations of the major dietary PUFAs, eicosapentaenoic acid, docohexaenoic acid, linoleic acid, and α-linolenic acid, with incident CVD and all-cause mortality in a population-based cohort. PUFAs in serum cholesterol esters were measured at baseline in 60-year-old Swedish women (n=2193) and men (n=2039). With the use of national registers, 484 incident CVD events (294 men and 190 women) and 456 all-cause deaths (265 men and 191 women) were identified during follow-up (median, 14.5 years) in individuals without prior CVD at baseline. Associations of PUFAs with CVD and mortality were evaluated with Cox proportional hazard models. In multivariable-adjusted models, 1-SD increases in eicosapentaenoic acid and docohexaenoic acid were associated with lower risk of incident CVD among women (hazard ratio [HR], 0.79 [95% confidence interval (CI), 0.64-0.97] and 0.74 [95% CI, 0.61-0.89], respectively). α-Linolenic acid was associated with moderately increased CVD risk in women (HR, 1.16; 95% CI, 1.02-1.32). Inverse associations with all-cause mortality were observed for eicosapentaenoic acid and docohexaenoic acid among all participants (HR, 0.81 [95% CI, 0.72-0.91] and 0.80 [95% CI, 0.72-0.89], respectively) and for linoleic acid in men (HR, 0.73; 95% CI, 0.64-0.83). Serum linoleic acid and very-long-chain n-3 PUFAs, partly reflecting vegetable oil and fish intake, respectively, were inversely associated with all-cause mortality. Inverse associations of eicosapentaenoic acid and docohexaenoic acid with incident CVD were observed only in women.


Psychotic disorders after childbirth in Nigerian women.
Fifty-seven consecutive cases of psychotic disorders arising within one year of childbirth and presenting over a two-year-period were studied prospectively. There was a preponderance of primigravidae. In 18% a family history of psychiatric disorders was obtained; 39% had suffered from previous psychotic episodes; 35% had suffered from obstetric complications; in 9% there was poor psychological adjustment to pregnancy. The majority (65%) was schizophrenic. Onset of symptoms in half the cases was within one month of delivery. The majority of cases (60%) presented in hospital within one month of onset of symptoms; there was a significant association between delay in arrival in hospital and prior treatment by religious or traditional healers. The immediate prognosis in terms of clinical recovery of the women was good. However, 53% ceased breast-feeding; seven of the children died, while another seven became physically ill. Eleven husbands left their wives. The implications of these findings are discussed.


Prospective study on the behaviour of the metalloprotease ADAMTS13 and of von Willebrand factor after bone marrow transplantation.
Thrombotic microangiopathies (TMAs) are rare but serious complications of bone marrow transplantation (BMT). Clinical manifestations are similar to those of thrombotic thrombocytopenic purpura (TTP), but prognosis is generally poorer despite plasma exchange. The enzymatic activity of the plasma metalloprotease ADAMTS13, which cleaves ultralarge thrombogenic multimers of von Willebrand factor (VWF) derived from activated endothelial cells, is very low or undetectable in patients with classic TTP, and protease deficiency is thought to play a mechanistic role in the formation of platelet thrombi in the microcirculation. This is the first prospective study to evaluate the incidence of TMA in 46 consecutively recruited patients undergoing autologous or allogeneic BMT and explore in parallel the behaviour of ADAMTS13, VWF antigen and VWF multimer size. The incidence of post-BMT TMA was 6% (three of 46); all cases occurred after allogeneic BMT. Compared with baseline values plasma ADAMTS13 activity was significantly reduced in patients undergoing BMT, particularly after the conditioning regimen (mean values: 50 +/- 22 vs. 77 +/- 32%; P < 0.0001). In the three patients who developed TMA, ADAMTS13 decreased after conditioning, but was very low in one case only (8%). VWF antigen levels progressively increased after the conditioning regimen (228 +/- 75 vs. 178 +/- 76% at baseline, P = 0.002). The mean proportion of high-molecular weight VWF multimers did not change in the various stages of BMT, even though ultralarge multimers were transiently found in same cases with and without TMA. Hence, the measurements evaluated in this study are not clinically useful to predict the occurrence of post-BMT TMA.


[The cultivation of Vibrio cholerae with green algae in an experiment].
Relationships between Vibrio cholerae of different origin and some serogroups with green algae Scenedesmus quadricauda in mineral medium at two temperatures have been experimentally studied. Differences in the relationships of various strains with green algae under the above-mentioned experimental conditions have been established. The study has shown that a decrease in the concentration and the death of vct+ and vct- vibrios of all strains under study occur in the linear phase of the development of algae. 3 V. cholerae strains, serogroups O139 (vct+) and O50 (vct-), have been shown to be capable of survival under the conditions mix cultivation with algae for 50-100 days. The perish of green algae is supposed to increase the survival time and multiplication of V. cholerae under experimental conditions.


Analysing cause of death during follow-up for non-muscle-invasive bladder cancer: is there a role for watchful waiting?
Non-muscle-invasive bladder cancer (NMIBC) patients often require multiple invasive procedures during follow-up. Surveillance guidelines do not adjust for increasing frailty or competing comorbidity. We aim to evaluate the influence of these factors on the natural history of NMIBC and whether this may have implications for appropriate follow-up schedules. NMIBC patients who died in a 3-year period while on cystoscopic surveillance were identified. Frailty was assessed using the Rockwood Clinical Frailty Scale (CFS): 1-3, no frailty; 4, vulnerable; 5-9, mild/severe frailty. Similarly, three-tier categorisations were performed for comorbidity (Charlson Comorbidity Index) and for anaesthetic risk (American Society of Anesthesiologists' [ASA] score). Of the 69 patients, 26 were categorised as no frailty, 20 as vulnerable and 13 as frail. There was no difference in the proportions of those with higher risk NMIBC between the categories. Increasing frailty was associated with reduced overall survival (median 59, 29 and 13 months; p < 0.05) but not recurrence-free survival (p = 0.98) or progression-free survival (p = 0.58). Similar results were obtained using the Charlson Comorbidity Index or ASA score. No frail patients with low/intermediate-risk NMIBC had clinically significant disease progression prior to death. Frail patients with CFS ≥ 4 were found to have similar complications due to bladder cancer itself (p = 0.48) yet almost three times as many complications following cystoscopic procedures during follow-up (p < 0.05). For frail patients with low risk of progression, protocol-driven cystoscopic surveillance may not improve survival and watchful waiting may be more appropriate. Further investigation is required to determine the feasibility of this approach.


Late congestive heart failure after hematopoietic cell transplantation.
To examine the independent roles of pre-hematopoietic cell transplantation (HCT) therapeutic exposures, transplantation-related conditioning, and comorbidities (pre- and post-HCT) in the development of late congestive heart failure (CHF) after HCT. This was a nested case-control design. Individuals with late CHF (diagnosed >or= 1 year after HCT) were identified from a cohort of 2,938 1+ year survivors who underwent transplantation at City of Hope National Medical Center, Duarte, CA. This cohort formed the sampling frame for selecting controls (without CHF) matched for age and year of HCT, donor source (allogeneic v autologous), and length of follow-up. Sixty patients with late CHF were identified; median age at HCT was 45.3 years (range, 16.6 to 68.6 years); median time to CHF was 3.0 years (range, 1.03 to 18.9 years); 68% received autologous HCT. Median ejection fraction was 36.9% (range, 15% to 53%). Compared with matched controls (n = 166), patients with late CHF received more cycles of pre-HCT chemotherapy (8.6 v 4.9 cycles; P < .01), had greater body mass index at HCT (28.4 v 26.2 kg/m(2); P = .01), greater lifetime anthracycline exposure (285.3 v 175.6 mg/m(2); P < .01), and were more likely to have multiple chronic comorbidities (30.0% v 13.9%; P < .01). Multivariable analysis revealed number of pre-HCT chemotherapy cycles (odds ratio [OR] = 1.2; P < .01), anthracycline dose >/= 250 mg/m(2) (OR = 3.2; P = .05), and two or more chronic comorbidities (OR = 4.3; P = .01) to be independently associated with late CHF. Pre-HCT exposure to anthracyclines and presence of comorbidities are primarily responsible for the risk associated with late CHF after HCT. Conditioning-related therapeutic exposure does not contribute significantly to the risk. These results form the basis for identifying high-risk individuals for targeted surveillance, as well as developing preventive strategies in the form of aggressive management of comorbidities.


Mechanisms involved in the rapid dissipation of plasma epinephrine response to bacterial endotoxin in conscious rats.
Conscious rats treated with bolus endotoxin (ET; 4.0 mg/kg) increased plasma epinephrine (Epi) 48-fold (from 134 +/- 5 to 6,545 +/- 1,607 pg/ml) at 30 min, but by 6 h this elevation was less than 9-fold above control (1,174 +/- 166 pg/ml). In contrast, plasma norepinephrine (NE) elevation (6.5-fold above control) was maintained during the protocol. The present study was designed to test the hypothesis that the decreased Epi response following ET was due to 1) depletion of adrenal Epi content such that adrenomedullary stimulation would not release Epi, 2) decreased Epi release with direct stimulation, i.e., desensitization of release, or 3) decreased afferent signals generated by ET itself. In these experiments an initial low ET dose (0.5 mg/kg) was followed 3 h later by a second dose of either the same (0.5 mg/kg) or greater (4.0 mg/kg) magnitude. Plasma Epi was elevated following the initial (low) dose but not following the same second (0.5 mg/kg) dose, whereas the second higher dose (4.0 mg/kg) resulted in elevated plasma Epi. This response to high dose was 60% less than that observed with 4.0 mg/kg as an initial dose. Just before the second ET bolus, there was no depletion of adrenal Epi content (P greater than 0.05 saline vs. ET treated), and direct nerve stimulation demonstrated enhanced rather than attenuated Epi release from the adrenal medulla (P less than 0.05 saline vs. ET treated). These results suggest that the decline in Epi following the ET-induced elevation may be mediated by a decrease in the afferent signal that initiates Epi release.


A guide on how to prevent falls injury in hospitals.
Falls among inpatients usually arise from a complex combination of risk factors, including the effects of longstanding and acute illness, the ageing process and the side effects of medication, combined with the unfamiliar environment of a hospital. This article outlines the range of interventions that can reduce the likelihood of falls and injury, and explains the value of the Patient Safety First 'How to' guide in supporting nurses to implement them. Patient and service improvement case studies are described.


The arrangement of muscle fibers and tendons in two muscles used for growth studies.
The arrangement of muscle fibres and tendons was examined in the soleus muscle of rats from 6 to 175 days post partum. The muscle was seen to change from a simple structure, with mean fibre length of approximately 90% of complete muscle length, to a unipennate structure, with mean fibre length of only about 60% of muscle length. The dog pectineus muscle was also investigated and found to have a bipennate structure throughout postnatal growth. The arrangement of muscle fibres in both these muscles is such that it might be difficult (particularly in the older animals) to cut a transverse section through all the fibres contained in the muscle; some fibres might not enter the plane of section. Results on muscle fibre number in these muscles at different ages may therefore be misleading.


Maladaptive coping with the infodemic and sleep disturbance in the COVID-19 pandemic.
COVID-19 is caused by a novel virus with an unknown aetiology. People across the globe are dealing with not only a health crisis but also an 'infodemic', a term coined by the World Health Organization to refer to the avalanche of contradictory information that is arousing widespread confusion and anxiety. This study aimed to examine the prevalence of anxiety and sleep disturbance at the early stage of the pandemic, and unveil the information coping process underlying differential susceptibility to COVID-19 infection anxiety and sleep disturbance. The participants were 1,270 adults (47% men, Mage = 42.82) from the UK and US who completed initial (Time 1) and follow-up (Time 2) surveys from 16 to 22 March and 18 to 24 May 2020, respectively. The prevalence of probable clinically relevant anxiety was 61% and 45% at the first and second time points, and more than half of the participants in this anxiety group also reported mild to severe sleep disturbance. Moreover, 41% of the participants perceived themselves as not having enough COVID-19-related information and reported higher levels of COVID-19 infection anxiety and sleep disturbance over time than those who perceived themselves as having enough of such information. Moderated mediation analysis identified two groups who were more vulnerable to both psychological problems: high blunters who sought COVID-19-related information online more frequently and high monitors who sought such information offline less frequently. These findings highlight the importance of a good match between information coping style and strategy deployment in dealing with an infodemic surrounding a novel disease.


Food consumption patterns in an adult urban population in Beirut, Lebanon.
To investigate, measure and assess the food consumption pattern of the adult population living in Beirut, Lebanon, and to identify inadequate or excessive intake of food groups particularly linked to non-communicable diseases. A cross-sectional food consumption survey was conducted in 2001. Dietary habits were assessed by means of a quantitative food-frequency questionnaire. Dietary survey of the urban population (Beirut). Random sample of 444 adult subjects (aged 25-54 years) in Beirut. The mean consumption of food by the study population was estimated to be 3,030 g day(-1), providing an energy intake of 2,523.57 kcal day(-1). Fat contributed 38.9% to the average daily energy intake, protein 13.4% and carbohydrates 47.2%. Mean consumption of fruits and vegetables was approximately 367 g day(-1) and 45.3% of subjects consumed less than the recommended 400 g daily. Cereals contributed 324.5 g day(-1), providing 35.0% of daily energy intake, with bread being the most highly consumed (146.2 g day(-1)) in this food group. The mean intake of meat and poultry products was 91.7 g day(-1) and provided 8.8% of daily energy intake, with consumption of butchery products especially beef being the highest (47.6 g day(-1)) followed by poultry (36.1 g day(-1)). A low consumption of fish was noted (19.7 g day(-1)), with 73.6% of subjects consuming less than the recommended 2 servings of fish per week. Dairy products contributed 243.1 g day(-1) or 10.9% of daily energy intake, and milk was the least consumed dairy product (56.8% of consumers). The intake of added fats and oils, excluding those in cooked recipes, was 20.4 g day(-1); olive oil was not used in cooking but was added solely at the table and its mean intake was 5 g day(-1). The consumption of butter was low (0.86 g day(-1)) and vegetable oil was the type of fat mostly used in cooking. The average intake of alcoholic beverages was low (33.6 g day(-1)), accounting for 0.7% of total energy intake. Women had significantly higher intakes of milk, dairy products, vegetables and coffee than men (P < 0.05). The percentage of women who reported the use of low-fat items was significantly higher than that of men. Younger people (25-34 years) ate significantly more meat, sugar, alcoholic beverages and soft drinks, and consumed significantly less cooked vegetables and legumes, than older ones (P < 0.05). The rather high contribution of fat to daily energy intake, the low intake of fish and the relatively high percentage of people consuming less than the recommended amount of fruits and vegetables observed in this study suggest that the adult Lebanese population is at increased risk of cardiovascular diseases, obesity and other non-communicable diseases, which provides the basis for recommending increased intakes of fish, particularly fatty fish, and fruits and vegetables.


Cyanides and their toxicity: a literature review.
Cyanide is a potent and rapidly-acting asphyxiant which prevents tissue utilization of oxygen by inhibition of the cellular respiratory enzyme, cytochrome oxidase. Inhalation or ingestion of cyanide produces reactions within a few seconds and death within minutes. Cyanide toxicity of dietary origin has been implicated in acute animal deaths and as major etiologic factors in toxic ataxic neuropathy in man and as a cause of vision failure in humans suffering from tobacco amblyopia and leber's hereditary optic atrophy. Diagnosis of cyanide toxicity may be confirmed by a variety of laboratory procedures, but accurate assay is essential for proper conclusions from analysis of animal tissues several hours after death or from human samples in instances of chronic dietary exposure. Biological detoxification of cyanide is available through several routes, and the application of sodium nitrite with sodium thiosulfate or administration of methylene blue are effective treatment procedure. The environmental availability of cyanide in its various forms necessitates an understanding of its pathophysiology and responsible management of hazardous situations.


Alpha-actinin-containing aggregates in transformed cells are highly dynamic structures.
Normal rat kidney cells infected with a Rous sarcoma virus (strain LA23) were used to study the dynamics of alpha-actinin-containing aggregates in transformed cells. Experiments were performed by microinjecting living cells with iodoacetamidotetramethylrhodamine alpha-actinin and allowing the fluorescent analogue to incorporate into cellular structures. Subsequent time-lapse recording indicated that the alpha-actinin-containing aggregates can undergo rapid formation, movement, and breakdown. In addition, experiments using the photobleaching recovery technique indicated that alpha-actinin molecules associated with the aggregates have a very high rate of exchange, whereas those associated with adhesion plaques in normal cells exchange much more slowly. The dynamic properties of alpha-actinin-containing aggregates may be closely related to the changes in cellular behavior upon oncogenic transformation.


Coronavirus interactions with the cellular autophagy machinery.
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is the most recent example of an emergent coronavirus that poses a significant threat to human health. Virus-host interactions play a major role in the viral life cycle and disease pathogenesis, and cellular pathways such as macroautophagy/autophagy prove to be either detrimental or beneficial to viral replication and maturation. Here, we describe the literature over the past twenty years describing autophagy-coronavirus interactions. There is evidence that many coronaviruses induce autophagy, although some of these viruses halt the progression of the pathway prior to autophagic degradation. In contrast, other coronaviruses usurp components of the autophagy pathway in a non-canonical fashion. Cataloging these virus-host interactions is crucial for understanding disease pathogenesis, especially with the global challenge of SARS-CoV-2 and COVID-19. With the recognition of autophagy inhibitors, including the controversial drug chloroquine, as possible treatments for COVID-19, understanding how autophagy affects the virus will be critical going forward. Abbreviations: 3-MA: 3-methyladenine (autophagy inhibitor); AKT/protein kinase B: AKT serine/threonine kinase; ATG: autophagy related; ATPase: adenosine triphosphatase; BMM: bone marrow macrophage; CGAS: cyclic GMP-AMP synthase; CHO: Chinese hamster ovary/cell line; CoV: coronaviruses; COVID-19: Coronavirus disease 2019; DMV: double-membrane vesicle; EAV: equine arteritis virus; EDEM1: ER degradation enhancing alpha-mannosidase like protein 1; ER: endoplasmic reticulum; ERAD: ER-associated degradation; GFP: green fluorescent protein; HCoV: human coronavirus; HIV: human immunodeficiency virus; HSV: herpes simplex virus; IBV: infectious bronchitis virus; IFN: interferon; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCoV: mouse coronavirus; MERS-CoV: Middle East respiratory syndrome coronavirus; MHV: mouse hepatitis virus; NBR1: NBR1 autophagy cargo receptor; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2 (autophagy receptor that directs cargo to phagophores); nsp: non-structural protein; OS9: OS9 endoplasmic reticulum lectin; PEDV: porcine epidemic diarrhea virus; PtdIns3K: class III phosphatidylinositol 3-kinase; PLP: papain-like protease; pMEF: primary mouse embryonic fibroblasts; SARS-CoV: severe acute respiratory syndrome coronavirus; SKP2: S-phase kinase associated protein 2; SQSTM1: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; ULK1: unc-51 like autophagy activating kinase 1; Vps: vacuolar protein sorting.


Methods in vascular infusion biotechnology in research with rodents.
Infusion of experimental compounds into the vascular system of rodents and the need to collect blood and other biological fluids from small animals comprise an area of emerging importance to biomedical research and drug discovery and development. The advances in the development of transgenic rodents coupled with technical progress in the manufacture and commercial availability of various catheters, swivels, tethers, infusion pumps, and sample collection systems that are described have enabled biomedical scientists to miniaturize vascular infusion and sample collection systems previously used in animal species larger than the rat or mouse. Use of these advanced, miniature vascular infusion systems in rodents is possible only when careful planning of experimental design, expert surgical technique, adequate postoperative care, and fundamental animal welfare considerations are meticulously taken into consideration. Use of these vascular infusion systems in rodents promotes animal welfare and scientific progress through the reduction and refinement of animal models.


Preoperative and perioperative predictors of the need for renal replacement therapy after orthotopic liver transplantation.
Acute renal failure developing after orthotopic liver transplantation (OLTx) requiring renal replacement heralds a poor prognosis. Our center has previously reported a 1-year survival of only 41.8%. We undertook this study to determine whether we could identify preoperative and perioperative factors that would predict which patients are at risk. OLTxs performed between January 1, 1996, and December 31, 2001, were included in our retrospective database review. Combined kidney-liver transplants or patients with preoperative renal replacement therapy (RRT) were excluded. A total of 724 OLTxs were studied, which were divided into group I: no RRT, n=637; group II: hemodialysis only post-OLTx, n=17; and group III: continuous RRT post-OLTx, n=70. Univariate and stepwise logistic multivariate analyses were performed. Preoperative serum creatinine greater than 1.9 mg/dL (odds ratio [OR] 3.57), preoperative blood urea nitrogen greater than 27 mg/dL (OR 2.68), intensive care unit stay more than 3 days (OR 10.23), and Model for End-Stage Liver Disease score greater than 21 (OR 2.5) were significant. A clinical prediction model was constructed: probability of requiring dialysis posttransplant=(-2.4586+1.2726 [creatinine >1.9] + 0.9858 [blood urea nitrogen >27] + 0.4574 [Model for End-Stage Liver Disease score >21] + 1.1625 [intensive care unit days >3]). A clinical prediction rule for patients with a score greater than 0.12 was applied to OLTx recipients who underwent transplantation in 2002. A total of 15 of 20 patients who received RRT and 111 of 121 who did not were correctly classified with the model. This model allowed us to identify patients at high risk for developing the need for RRT postoperatively. Strategies for these patients to prevent or ameliorate acute renal failure and reduce the need for RRT postoperatively are needed.


The 2,2',4,4',5,5'-hexachlorobiphenyl-enhanced degradation of connexin 43 involves both proteasomal and lysosomal activities.
One of the toxic effects of non-dioxin-like polychlorinated biphenyls (NDL-PCBs) is the acute inhibition of gap junctional intercellular communication (GJIC), an event possibly associated with tumor promotion. The model NDL-PCB-2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153)-induces a sustained GJIC inhibition in rat liver epithelial WB-F344 cells. As this effect might be related to deregulation of connexin 43 (Cx43) synthesis, trafficking, or degradation, we investigated the impact of PCB 153 on these events. Although PCB 153 had no effect on Cx43 mRNA levels, it induced a gradual loss of Cx43 protein and significantly decreased the amount of gap junction plaques in plasma membrane. PCB 153 contributed to extracellular signal-regulated kinases 1 and 2 (ERK1/2)-dependent accumulation of hyperphosphorylated Cx43-P3 form, thus indicating that ERK1/2 activation by PCB 153 might contribute to its effects on Cx43 internalization or degradation. Inhibition of either proteasomes or lysosomes with their specific inhibitors largely restored total Cx43 protein levels, thus suggesting that both proteasomes and lysosomes may participate in the PCB 153-enhanced Cx43 internalization and degradation. However, neither the proteasomal nor the lysosomal inhibitors restored normal GJIC or number/size of gap junction plaques. Finally, PCB 153 also interfered with restoration of gap junction plaques following the inhibition of Cx43 transport to plasma membrane. Taken together, multiple modes of action seem to contribute to downregulation of Cx43 in PCB 153-treated rat liver epithelial cells. The enhanced degradation of Cx43, together with persistent inhibition of GJIC, might contribute to tumor-promoting effects of NDL-PCBs.


Trabecular Metal Cones Combined With Short Cemented Stem Allow Favorable Outcomes in Aseptic Revision Total Knee Arthroplasty.
The purpose of this study was to compare the functional outcomes and implant survivorship at a minimum of 5 years of follow-up of several reconstruction techniques with or without metaphyseal cone and stems of variable length. A retrospective comparative matched analysis was performed from 2 prospectively collected databases. Only patients who underwent revision total knee arthroplasty procedures for aseptic causes using a single design of rotating hinge knee with a minimum of 5 years of follow-up were analyzed. Patients were separated into 3 groups: trabecular metal (TM) cones + short cemented stems (TM + short stem [SS]), TM cones + long uncemented stems (TM + long stem [LS]), and no cone (NC) + long uncemented stems (NC + LS). A matching process based on age (±5 years) was realized. About 99 patients were included; 33 in the TM + SS group, 33 in the TM + LS group, and 33 in the NC + LS group. The mean time of follow-up was 9.3 years. A significant difference of the improvement of subscale pain, symptom, activities of daily living, quality of life of the Knee Injury and Osteoarthritis Outcome score and knee, function of the Knee Society Score was observed in favor of TM + SS group compared with the 2 other groups. At 8 years of survivorship, the components free of revision for any cause were 90.9% for the TM + SS group, 84.9% for the TM + LS group, and 90.6% for the NC + LS group. The use of a short cemented tibial stem combined with a TM cone in revision total knee arthroplasty offers identical survival rate with better functional outcome compared with the use of a long uncemented stem associated with TM cones or metallic augments at a minimum of 5 years of follow-up.


A novel distyryl boron dipyrromethene with two functional tags for site-specific bioorthogonal photosensitisation towards targeted photodynamic therapy.
A distyryl boron dipyrromethene based photosensitiser substituted with 1,2,4,5-tetrazine and alkyne moieties was prepared. Through site-specific bioorthogonal reactions with the complementary functional tags anchored on the membrane of A431 human epidermoid carcinoma cells, this versatile photosensitiser exhibited enhanced cellular uptake and photocytotoxicity. The bioorthogonal ligation was also demonstrated in tumour-bearing nude mice.


A case of sarcoidosis accompanying squamous cell carcinoma in the mandibular gingiva.
A 51-year-old man with a history of gingival cancer two years previously was referred to our hospital for further examination of chest abnormal shadow. Bilateral hilar and mediastinal lymphadenopathy, diffuse small nodular opacities and pleural nodules were observed in chest high resolution CT. Serum angiotensin converting enzyme and lysozyme were elevated. Transbronchial lung biopsy specimens demonstrated non-caseous granuloma. CD4-positive lymphocytes were increased in broncho-alveolar lavage (CD4/CD8 ratio 5.47). The patient was diagnosed as having sarcoidosis. Radiological findings were improved and serum angiotensin converting enzyme level was decreased to within the normal range by corticosteroid therapy (prednisolone 30 mg/day). This is the first report of sarcoidosis accompanying the gingival cancer.


The Readiness For Interprofessional Education (IPE) In The School Setting Among The Internship Students Of Applied Medical Sciences At Taibah University.
The study aims to assess the readiness of Interprofessional Education (IPE) in the school setting among the Internship Students of Applied Medical Sciences at Taibah University. This study utilized a survey targeting internship students of Applied Medical Sciences; departments Diagnostic Radiologic Technology, Medical Laboratory Technology, and Clinical Nutrition, at Taibah University. We used a modified Readiness for Inter-professional Learning Scale (RIPLS) survey to collect the data of this study. Data were analyzed using SPSS software version 21. A 100 surveys distributed, 40 were returned. Most of the internship students (88.7%) agreed that IPE could make them more collaborated and can enhance teamwork skill to them. A total of 36.25% of the internship student agreed, and 50.01% disagree about the negative professional identity of the IPE. 86.66% of the internship student agreed, and 50.01% disagree about the positive professional identity of the IPE. They responded that sharing learning with other health care professionals will help them to communicate better with patients and other professionals and to improve practice. 65.84% of the internship student agreed, and 23.75% disagreed about the impact of IPE on their role and responsibility. The difference between the internship student at the end level of the internship and internship student at the beginning level of the internship, towards the positive thinking about other healthcare professionals was 0.015. The study concluded that there was a readiness of IPE in the school setting among the Internship Students Students of Applied Medical Sciences at Taibah University. The majority of the internship student agreed that IPE could make them more collaborated and can enhance teamwork skill to them. There was a significant difference between the internship student at the end level of the internship and internship student at the beginning level of the internship, towards the positive thinking about other healthcare professionals.


A domain operator for binary morphological processing.
A new class of morphological operators, the domain operator, is proposed for binary images. The operation is defined with a domain function based on the index function of fuzzy sets. With appropriate definition of the connection weights, the domain operator can implement conventional morphological operations such as dilation, erosion, opening, and closing, as well as other image processing functions such as noise reduction, edge detection, and clump splitting.


Jointly learning word embeddings using a corpus and a knowledge base.
Methods for representing the meaning of words in vector spaces purely using the information distributed in text corpora have proved to be very valuable in various text mining and natural language processing (NLP) tasks. However, these methods still disregard the valuable semantic relational structure between words in co-occurring contexts. These beneficial semantic relational structures are contained in manually-created knowledge bases (KBs) such as ontologies and semantic lexicons, where the meanings of words are represented by defining the various relationships that exist among those words. We combine the knowledge in both a corpus and a KB to learn better word embeddings. Specifically, we propose a joint word representation learning method that uses the knowledge in the KBs, and simultaneously predicts the co-occurrences of two words in a corpus context. In particular, we use the corpus to define our objective function subject to the relational constrains derived from the KB. We further utilise the corpus co-occurrence statistics to propose two novel approaches, Nearest Neighbour Expansion (NNE) and Hedged Nearest Neighbour Expansion (HNE), that dynamically expand the KB and therefore derive more constraints that guide the optimisation process. Our experimental results over a wide-range of benchmark tasks demonstrate that the proposed method statistically significantly improves the accuracy of the word embeddings learnt. It outperforms a corpus-only baseline and reports an improvement of a number of previously proposed methods that incorporate corpora and KBs in both semantic similarity prediction and word analogy detection tasks.


EROS study: evaluation between high-dose-rate and low-dose-rate vaginal interventional radiotherapy (brachytherapy) in terms of overall survival and rate of stenosis.
To compare the survival and toxicity outcomes in patients with endometrial cancer treated with either high-dose-rate (HDR) or low-dose-rate (LDR) vaginal brachytherapy (VBT) following external beam radiotherapy (EBRT). From January 2000 to December 2014, patients with endometrial cancer after radical hysterectomy with/without pelvic and/or para-aortic lymphadenectomy were treated with adjuvant EBRT (45 Gy, 1.8 Gy/day to the whole pelvis) and subsequent VBT boost (HDR dose of 7 Gy in one fraction or LDR VBT dose of 25 Gy). The dose was prescribed at 0.5 cm from the surface of the applicator and the proximal half to two-thirds of the vagina was irradiated. The outcomes of patients were evaluated in terms of local control (LC), overall survival (OS), and rates of adverse events. We analyzed data of 200 patients treated with EBRT followed by HDR VBT boost in 78 patients and LDR VBT boost in 122 patients. With a median follow-up of 25 months (range, 6-163), 5-year OS was 98% and 97% in the LDR and HDR groups, respectively (p = 0.37). The 5-year LC was similar (93% in both groups) (p = 0.81). In multivariate analyses, none of the factors assessed (age, stage, grade) impacted OS (p = 0.37) or LC (p = 0.81). Patients treated with LDR VBT after EBRT had higher rates of acute gastrointestinal toxicity. No differences were found in acute genitourinary or hematological toxicities. Late toxicity such as vaginal stenosis was registered during regular follow-up visits and was similar in the two groups (p = 0.67). In our analysis, there were no differences in terms of OS and late toxicity outcomes for patients receiving LDR or HDR VBT. HDR VBT is a safe technique in comparison to LDR VBT.


The association of insomnia and depressive symptoms with all-cause mortality among middle-aged and old adults.
Insomnia and depressive symptoms are commonly reported by adults and have independently been found to be associated with mortality, though contrasting findings are reported. Given the high comorbidity and interrelatedness between these symptoms, we tested whether insomnia symptoms explain risk of death independent of depressive symptoms. We examined insomnia symptoms and depressive symptoms, in addition to other health and demographic covariates, as predictors of all-cause mortality. The sample included 15 418 adults aged 51 and older drawn from a nationally representative, population-based study of adults in the United States, the Health and Retirement Study. Cox survival models were used to analyze time to death between the 2002 and 2014 study waves (5 waves). Controlling for health and demographic covariates, in 3 separate models, depressive symptoms and insomnia symptoms were independently and then together considered as risk factors for all-cause mortality (drawn from the National Death Index). After adjustment for covariates, insomnia symptoms (HR = 1.10, CI:1.07-1.13) and depressive symptoms (HR = 1.14, CI:1.12-1.16) each were associated with a greater hazard of death. When considered together, however, depressive symptoms fully accounted for the association between insomnia symptoms and mortality. Though their effects are small relative to health and demographic characteristics, both insomnia symptoms and depressive symptoms were associated with a greater hazard of death. Yet depressive symptoms accounted for the insomnia association when both were considered in the model. Screening for depression and providing validated treatments may reduce mortality risk in old adults with depressive symptoms.


A selective IgA deficiency in a boy who presented recurrent parotitis.
Recurrent parotitis is a non-obstructive, non-suppurative inflammatory disease which is characterized by unilateral or bilateral parotid gland swelling attacks. It is also known as juvenile recurrent parotitis. Although the etiology is unknown, congenital malformations of the ductus, genetic predisposition, infections, allergies, autoimmune diseases, and some immune deficiencies are blamed. Here, we present a case report of recurrent parotitis with selective immunoglobulin A deficiency in a six-year-old boy. The patient was presented to us with a new episode of swelling of left parotid region. In the last 2 years, the patient suffered from recurrent parotitis which lasted for approximately 5 days in ten individual episodes.


Congenital diaphragmatic hernia.
CDH is a developmental abnormality resulting in a diaphragmatic defect which permits abdominal viscera to enter the chest. Most cases occur through the posterolateral foramen of Bochdalek. The mortality rate associated with CDH remains high due to the presence of associated anomalies, pulmonary hypoplasia, and pulmonary hypertension in those with adequate lung parenchyma to initially support life. A large number of approaches have been used to manage these infants, including delayed surgical repair, pharmacologic treatment of pulmonary hypertension, high frequency oscillation, ECMO, and surfactant therapy. New, and as yet unproven, innovations such as permissive hypercapnea, fetal surgery, and liquid ventilation may provide greater hope in the future for severely affected infants. Although most surviving children with CDH do well, a significant incidence of gastrointestinal and neurologic morbidity still exists.


[Immunocorrecting and protective effect of proteolytic enzymes on antibody formation in mice in staphylococcal infection and antibiotic treatment].
The impact of proteolytic enzymes on the humoral immune response, survival rate and mean survival time of mice, infected with S. aureus culture and receiving antibiotics was studied. Infection with staphylococcal suppressed the formation of antibodies to sheep red blood cells. Ampicillin made this immunosuppression even more pronounced, while gentamicin produced practically no effect on the degree of immunosuppression in the infected animals. Proteolytic enzymes terrilytin and terridecase exhibited immunocorrecting properties when used in combination with antibiotics. Terridecase, the immobilized form of the enzyme proved to have the highest activity. In experimental generalized staphylococcal infection all preparations under study produced a protective effect. The maximum effect was noted after the use of ampicillin in combination with terridecase.


Heterozygous CAV1 frameshift mutations (MIM 601047) in patients with atypical partial lipodystrophy and hypertriglyceridemia.
Mice with a deleted Cav1 gene encoding caveolin-1 develop adipocyte abnormalities and insulin resistance. From genomic DNA of patients with atypical lipodystrophy and hypertriglyceridemia who had no mutations in any known lipodystrophy gene, we used DNA sequence analysis to screen the coding regions of human CAV1 (MIM 601047). We found a heterozygous frameshift mutation in CAV1, designated I134fsdelA-X137, in a female patient who had atypical partial lipodystrophy, with subcutaneous fat loss affecting the upper part of her body and face, but sparing her legs, gluteal region and visceral fat stores. She had severe type 5 hyperlipoproteinemia, with recurrent pancreatitis. In addition, she had some atypical features, including congenital cataracts and neurological findings. Her father was also heterozygous for this mutation, and had a similar pattern of fat redistribution, hypertriglyceridemia and congenital cataracts, with milder neurological involvement. An unrelated patient had a different heterozygous frameshift mutation in the CAV1 gene, designated -88delC. He also had a partial lipodystrophy phenotype, with subcutaneous fat loss affecting the arms, legs and gluteal region, but sparing his face, neck and visceral fat stores. He also had severe type 5 hyperlipoproteinemia, with recurrent pancreatitis; however he had no clinically apparent neurological manifestations. The mutations were absent from the genomes of 1063 healthy individuals. Thus, very rare CAV1 frameshift mutations appear to be associated with atypical lipodystrophy and hypertriglyceridemia.


Reactions of C-terminal omega-amino acid residues in liquid hydrogen fluoride.
The benzyl-ester bond linking the C-terminal delta-aminovaleric acid residue of a peptide to a polymeric support was cleaved with liquid hydrogen fluoride in the presence of anisole, added as scavenger. Instead of the expected peptide with a free carboxyl group at the C-terminus, a peptide terminating in a ketone derivative was obtained. The unusual extent of this known side-reaction was attributed to the effect of the distance between the amino group and the carboxyl group in the C-terminal residue. The results of model experiments corroborated this view.


[The Ineq-Cities research project on urban health inequalities: knowledge dissemination and transfer in Spain].
The Ineq-Cities project analyzed inequalities in mortality in small areas and described interventions to reduce inequalities in health in 16 European cities. This field note describes the dissemination of the project in Spain. In accordance with the recommendations of the project, the objective was to translate relevant results to key stakeholders - mainly technical staff, municipal officers and local social agents - and to provide an introduction to urban inequalities in health and strategies to address them. Twenty-four workshops were given, attended by more than 350 professionals from 92 municipalities. Knowledge dissemination consisted of the publication of a short book on inequalities in health and the approach to this problem in cities and three articles in nonspecialized media, a proposal for a municipal motion, and knowledge dissemination activities in social networks. Users rated these activities highly and stressed the need to systematize these products. This process may have contributed to the inclusion of health inequalities in the political agenda and to the training of officers to correct them.


What is the significance of nasal involvement in nasopharyngeal carcinoma?
The purpose of this study was to differentiate the patterns of nasal fossa involvement in nasopharyngeal carcinoma (NPC) and to clarify its prognostic influence on local control and survival after radiation therapy. Between November 1989 and July 1991, 218 patients with histologically proven local-regional NPC were treated with radiotherapy following the protocol at the Department of Radiation Oncology, Cancer Hospital, Shantou University School of Medicine. All patients had pretreatment CT scans. Fiberoptic endoscopic examination was performed every week during treatment and at the time of every follow-up visit to define the initial extent of disease and to evaluate treatment response. No chemotherapy or brachytherapy was given. Of the 218 patients, 87 had nasal involvement. Sixty of them had a pattern of mucosal infiltration (MI), another 27 had an exophytic protruding (EP) component. The likelihood of residual disease after irradiation, the local relapse rate, 5-year freedom from progression rate (FFP), and death rate associated with local relapse (DRALR) of MI and EP were 36.7% vs. 3.7%, 30.0% vs. 7.4%, 26.7% vs. 51.8%, and 25.0% vs. 3.7% with p<0.004, p<0.005, p<0.02, and p<0.03, respectively. Multivariate analysis in this selected group demonstrated that infiltration of nasal fossa mucosa was an independent prognostic factor on primary control and freedom from progression. Differentiation of nasal fossa involvement according to MI or EP is of value in predicting the outcome of treatment. We suggest that only the MI group should be considered as nasal involvement in the staging of NPC.


Wild carnivores, domestic dogs and ticks: shared parasitism in the Brazilian Cerrado.
The increase of contact between natural and rural areas is prominent in Brazil, due to agricultural activities and concern with the environmental conservation. In this context, domestic animals, wild fauna and humans are exposed to mutual exchange of parasites, microorganisms and diseases. We studied tick parasitism of wild carnivores and domestic dogs, and the environmental of questing ticks, in extensive cattle ranch areas intermingled with natural vegetation, and in a natural reserve, both in a region of Cerrado biome, Midwestern Brazil. From 2008 to 2015, we inspected 119 wild carnivores from nine species, and collected six tick species (Amblyomma sculptum, Amblyomma ovale, Amblyomma dubitatum, Amblyomma tigrinum, Dermacentor nitens and Rhipicephalus microplus). The most numerous and infested hosts were Cerdocyon thous, Lycalopex vetulus, Chrysocyon brachyurus, Puma concolor and Conepatus amazonicus. From 139 domestic dogs, we collected A. sculptum, Rhipicephalus sanguineus and R. microplus. From vegetation, samplings resulted in A. sculptum, A. dubitatum, A. ovale, Amblyomma rotundatum and R. microplus, with dominance of A. sculptum. Domestics and wild animals presented high overlapping of infestations by A. sculptum, a generalist and anthropophilic tick species. This tick is the most important vector of the Brazilian spotted fever, a lethal human disease. This fact elicits attention and requires efforts to monitor the presence of pathogens vectored by ticks circulating in this type of agroecosystem, including in other regions of the Brazil, because the most of the natural vegetation remaining have been increasingly immersed in pastures and agricultural matrix.


[Clinical variants of amyotrophic lateral sclerosis: hemiplegic type of ALS and Mills syndrome. A critical review].
According to the clinical classification of amyotrophic lateral sclerosis by Hemmer its "hemiplegic type" is described from two observations in 37 personal cases. The peculiar difficulties of differential diagnosis especially with the hemiplegic type of multiple sclerosis in two further cases are discussed in detail. Four cases of "Mills' syndrome" are compared. "Mills' syndrome" has been assumed to be a slowly progressive, unilateral ascending or descending variant of amyotrophic lateral sclerosis. A study of Mills' original papers and evaluation of personal observations leads to a more critical assessment. In Mills' original cases, widely different entities such as multiple sclerosis, syphilis, and parkinsonism are included besides amyotrophic lateral sclerosis. In the light of the investigations presented here, Mills' syndrome seems to be merely an obsolete clinical term.


An Analysis of Central Residues Between Ligand-Bound and Ligand-Free Protein Structures Based on Network Approach.
Depiction of protein structures as networks of interacting residues has enabled us to understand the structure and function of the protein. Previous investigations on closeness centrality have identified protein functional sites from three- dimensional structures. It is well recognized that ligand binding to a receptor protein induces a wide range of structural changes. An interesting question is how central residues function during conformational changes triggered during ligand binding? The aim of this study is to comprehend at what extent central residues change during ligand binding to receptor proteins. To determine this, we examined 37 pairs of protein structures consisting of ligand-bound and ligand-free forms. These protein structures were modelled as an undirected network and significant central residues were obtained using residue centrality measures. In addition to these, the basic network parameters were also analysed. On analysing the residue centrality measures, we observed that 60% of central residues were common in both the ligand-bound and ligand-free states. The geometry of the central residues revealed that they were situated closer to the protein center of the mass. Finally, we demonstrated the effectiveness of central residues in amino acids substitutions and in the evolution itself. The closeness centrality was also analyzed among different protein domain sizes and the values gradually declined from single-domains to multi-domain proteins suggesting that the network has potential for hierarchical organization. Betweenness centrality measure was also used to determine the central residues and 31% of these residues were common between the holo/apo states. Findings reveal that central residues play a significant role in determining the functional properties of proteins. These results have implications in predicting binding/active site residues, specifically in the context of drug designing, if additional information concerning ligand binding is exploited.


Older adults with Alzheimer's disease in a faith community.
In the first phase of this study, focus groups were conducted with 12 clergy to explore how to meet the needs of Alzheimer's disease patients and their families. The clergy reported that although they do reach out to these families, they have not received formal training, so they often do not know what families need. Members of their congregations who are trained in working with Alzheimer's patients need to partner with the clergy in reaching out to these families. Although this article mainly focuses on the clergy's perspective, in the second phase of the study, caregivers and early-stage Alzheimer's patients were asked to describe their experiences of spiritual connections related to Alzheimer's disease.


The effects of a ration change from a total mixed ration to pasture on rumen fermentation, volatile fatty acid absorption characteristics, and morphology of dairy cows.
To investigate the effect of the change from a concentrate and silage-based ration (total mixed ration, TMR) to a pasture-based ration, a 10-wk trial (wk 1-10) was performed, including 10 rumen- and duodenum-fistulated German Holstein dairy cows (182±24 d in milk, 23.5±3.5kg of milk/d; mean ± standard deviation). The cows were divided in either a pasture group (PG, n=5) or a confinement group (CG, n=5). The CG stayed on a TMR-based ration (35% corn silage, 35% grass silage, 30% concentrate; dry matter basis), whereas the PG was gradually transitioned from a TMR to a pasture-based ration (wk 1: TMR only; wk 2: 3 h/d on pasture wk 3 and 4: 12 h/d on pasture wk 5-10: pasture only). Ruminal pH, volatile fatty acids (VFA), NH3-N, and lipopolysaccharide (LPS) concentrations were measured in rumen fluid samples collected medially and ventrally on a weekly basis. Ruminal pH was continuously recorded during 1 to 4 consecutive days each week using ruminal pH measuring devices. In wk 1, 5, and 10, rumen contents were evacuated and weighed, papillae were collected from 3 locations in the rumen, and subsequently a VFA absorption test was performed. In the PG, mean rumen pH and molar acetate proportions decreased, and molar butyrate proportions increased continuously over the course of the trial, which can most likely be ascribed to an increased intake of rapidly fermentable carbohydrates. During the first weeks on a full grazing ration (wk 5-7), variation of rumen pH decreased, and in wk 5 a lower rumen content, papillae surface area, and potential for VFA absorption were observed. In wk 8 to 10, variation of rumen pH and total VFA concentrations increased again, and acetate/propionate ratio decreased. In wk-10 rumen content, papillae area and VFA absorption characteristics similar to initial levels were observed. Although continuous rumen pH assessments and LPS concentrations did not reveal an increased risk for subacute rumen acidosis (SARA) during the adaption period, histopathology of rumen papillae and potential for VFA absorption indicated a possible risk for rumen health. An increased risk for SARA was observed in wk 9 and 10 in the PG, but rumen LPS concentrations and histopathology were not adversely affected. Results of the present study suggest that after behavioral and metabolic adaptation to the transition from a TMR to a pasture-based ration, no adverse effects on rumen morphology and absorption capacity occurred, although rumen pH after adaptation to pasture indicated increased risk of SARA.


Electrophysiologic disturbances during daytime in patients with restless legs syndrome: further evidence of cognitive dysfunction?
It has been reported that patients with restless legs syndrome (RLS) may have cognitive deficit. The authors performed EEG and ERP analysis during daytime to identify electrophysiologic relations with cognitive dysfunction in unmedicated RLS patients. Seventeen drug naive RLS patients (53.7±9.6 years) and 13 age-matched healthy controls participated in the present study. EEG was recorded during the waking-resting state and during a visual oddball task. RLS severities were determined using the International RLS Severity Scale. Stanford sleepiness scale (SSS) and bothersomeness visual analog scale (VAS) scores were determined immediately after ERP sessions. EEG power spectra and P300 amplitude and latency were compared for patients and controls. Clinical variables were correlated with P300 findings. Waking-resting EEG showed that RLS patients had significantly higher beta activity in frontocentral regions than controls. SSS scores were not different in the two groups. But the bothersomeness VAS scores of RLS patients were significantly higher than those of controls. Furthermore, P300 latency was significantly longer in patients, and patients had significantly lower P300 amplitudes in frontal and central locations. In addition, P300 latency was found to be significantly correlated with bothersomeness during the ERP test, whereas P300 amplitude showed no such tendency. Our study supports the notion that RLS patients have an underlying cognitive dysfunction. Significant correlations found between P300 latency and bothersomeness, a lack of sleepiness during the ERP test, and increased beta activity in resting state EEGs suggest that a combination of inattention and cortical dysfunction underlie cognitive dysfunction in RLS.


A clinical and radiological profile of neuromyelitis optica and spectrum disorders in an Indian cohort.
There is insufficient data on the clinical and radiological features of neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) from India. The objective of the following study is to examine the clinico-radiological features of NMO and NMOSD in an Indian cohort. This retrospective study included 44 consecutive patients who (1) satisfied the 2006 Wingerchuk criteria for NMO (16 seropositive and 7 seronegative); or (2) had isolated or recurrent optic neuritis (ON) with seropositivity (n = 4); or (3) had isolated or recurrent myelitis with seropositivity (n = 17). The female:male ratio was 7.8:1 with median age of onset 26.5 (range 8-72). Annualized relapse rate (ARR) was comparable across all groups (F [3, 40] = 0.938 and P = 0.431). Various presentations other than ON and myelitis were noted. All 40 patients with myelitis had spinal cord lesions involving ≥3 vertebral segments during the course of the disease. Cervicomedullary involvement was seen in 32.5% (13/40) patients. Brain magnetic resonance imaging was available for 40 patients; eight of these (20%) had brain lesions in locations described in multiple sclerosis (MS), 27.5% (11/40) had lesions at sites unusual for MS and 52.5% (21/40) had normal brain imaging. NMO and NMOSD patients in this cohort have comparable ARR regardless of clinical presentation, supporting the emerging trend of treating all patients with immunotherapeutic agents at an early stage. Varied presentations seen in NMO and NMOSD highlight the need for a high index of suspicion for NMO in demyelinating episodes not classical for MS.


First report from the Asian Rotavirus Surveillance Network.
Rotavirus remains the most common cause of severe, dehydrating diarrhea among children worldwide. Several rotavirus vaccines are under development. Decisions about new vaccine introduction will require reliable data on disease impact. The Asian Rotavirus Surveillance Network, begun in 2000 to facilitate collection of these data, is a regional collaboration of 36 hospitals in nine countries or areas that conduct surveillance for rotavirus hospitalizations using a uniform World Health Organization protocol. We summarize the Network's organization and experience from August 2001 through July 2002. During this period, 45% of acute diarrheal hospitalizations among children 0-5 years were attributable to rotavirus, higher than previous estimates. Rotavirus was detected in all sites year-round. This network is a novel, regional approach to surveillance for vaccine-preventable diseases. Such a network should provide increased visibility and advocacy, enable more efficient data collection, facilitate training, and serve as the paradigm for rotavirus surveillance activities in other regions.


Social inclusion and exclusion of people with mental illness in Timor-Leste: a qualitative investigation with multiple stakeholders.
Social inclusion is a human right for all people, including people with mental illness. It is also an important part of recovery from mental illness. In Timor-Leste, no research has investigated the social experiences of people with mental illness and their families. To fill this knowledge gap and inform ongoing mental health system strengthening, we investigated the experiences of social inclusion and exclusion of people with mental illness and their families in Timor-Leste. Eighty-five participants from the following stakeholder groups across multiple locations in Timor-Leste were interviewed: (1) people with mental illness and their families; (2) mental health and social service providers; (3) government decision makers; (4) civil society members; and (5) other community members. Framework analysis was used to analyse interview transcripts. People with mental illness in Timor-Leste were found to face widespread, multi-faceted sociocultural, economic and political exclusion. People with mental illness were stigmatised as a consequence of beliefs that they were dangerous and lacked capacity, and experienced instances of bullying, physical and sexual violence, and confinement. Several barriers to formal employment, educational, social protection and legal systems were identified. Experiences of social inclusion for people with mental illness were also described at family and community levels. People with mental illness were included through family and community structures that promoted unity and acceptance. They also had opportunities to participate in activities surrounding family life and livelihoods that contributed to intergenerational well-being. Some, but not all, Timorese people with mental illness benefited from disability-inclusive programming and policies, including the disability pension, training programs and peer support. These findings highlight the need to combat social exclusion of people with mental illness and their families by harnessing local Timorese sociocultural strengths. Such an approach could centre around people with mental illness and their families to: increase population mental health awareness; bolster rights-based and culturally-grounded mental health services; and promote inclusive and accessible services and systems across sectors.


The effect of primary-canine extraction on the IMPA.
One can expect to lose IMPA or arch circumference after extraction of the primary canines, if the child presents with an initial FMIA of 64 degrees or less. If the initial FMA is 28 degrees or greater, one can probably expect to lose IMPA, if the primary canines are extracted. One may tentatively suggest that in patients with normal FMA's and FMIA's, the extraction of the primary canines will not appreciably affect the IMPA. Space maintainers may not be needed in such cases. Of the twenty-two patients who had primary canines extracted, ten patients lost IMPA and twelve patients had no change or an increase of IMPA. The findings of this study should be replicated with a larger patient sample.


Immobilized phage proteins for specific detection of staphylococci.
Rapid, specific detection of pathogenic bacteria remains a major challenge in infectious disease diagnostics. Bacteriophages can show genus- or even species-level specificity and have been developed for biosensing purposes, but the possibility of using individual phage proteins for detection has not been fully explored. This work exploits the ability of specific phage proteins, the endolysins LysK and Φ11, and the bacteriocin lysostaphin, fixed on silicon wafers to bind staphylococci. The proteins show activity against eight tested clinical isolates of S. aureus and to S. epidermidis, but no binding to Escherichia coli and limited binding to Micrococcus. Binding was quantified by clearing assays in solution and by functionalization of silicon wafers followed by light microscopy. Bacterial binding densities on functionalized surfaces were ~3 cells/100 μm(2). The small size of the proteins makes the system robust and easy to handle, and the principle is generalizable to many different biosensor platforms, including label-free systems such as optical microresonators.


Heart rate variability analysis of patients with idiopathic left ventricular outflow tract tachycardia: role of triggered activity.
There have been several reports with respect to idiopathic ventricular tachycardias (VTs) originating from the left ventricular outflow tract (LVOT). A previous report suggested that triggered activity plays a partial role in idiopathic LVOT tachycardia from the electrophysiological as well as the electropharmacological viewpoint. However, the exact role of triggered activity in this type of VT remains unknown. In the present study the relationship of the frequency of premature ventricular contractions (PVCs) and heart rate was examined and heart rate variability (HRV) was analyzed in 2 cases of LVOT tachycardia using 24-h Holter electrocardiographic (ECG) monitoring. The relation between the PVCs frequency and heart rate showed a persistently positive correlation, indicating frequent PVCs as heart rate increased. In HRV analysis, NN50(%), a time-domain variable of parasympathetic activity, showed no change prior to ventricular arrhythmias. In frequency-domain analysis of HRV, the high frequency (HF) component tended to fall prior to repetitive PVCs and VTs. The ratio of the low frequency to high frequency (LF/HF) components increased prior to single PVCs, repetitive PVCs and VTs. Sympathetic predominance predisposes the genesis of these kinds of arrhythmias originating from the LVOT and it is suggested that triggered activity plays an important role in LVOT tachycardia, at least in its initiation.


Isoliquiritigenin, an active ingredient of Glycyrrhiza, elicits antinociceptive effects via inhibition of Nav channels.
Glycyrrhiza extract has been used for the treatment of oral and gastric ulcers, but the analgesic mechanism remains unknown. In the present study, we investigated the effects of isoliquiritigenin, an active ingredient of Glycyrrhiza, on Nav channels in vitro and nociceptive behaviors in vivo. In an autopatch-clamp study, isoliquiritigenin inhibited the currents of Nav1.1, Nav1.3, Nav1.6, Nav1.7, and Nav1.8 in a channel expression system. In small- and medium-sized cultured trigeminal ganglion neurons, the compound suppressed Nav currents in many neurons (78%) and Kv currents in all neurons, dose-dependently. In current-clamp mode, isoliquiritigenin blocked action potential generation in many neurons (64%), but it conversely accelerated action potential generation in the remaining neurons. The opposing effects on action potentials were reproduced in a computational simulation of a modified Hodgkin-Huxley-based model, based on the electrophysiological data. In behavioral experiments, local treatment with isoliquiritigenin suppressed nociceptive behaviors in response to oral ulcer development or nociceptive TRP channel agonists in the oral mucosa and hind paw. These results suggest that isoliquiritigenin exerts an analgesic effect predominantly via inhibitory action on Nav channels on sensory nociceptive fibers. This pharmacological mechanism indicates that isoliquiritigenin is useful for pain relief and provides scientific evidence for Glycyrrhiza at the ingredient level.


Anesthesia for laparoscopic general surgery. A special review.
Laparoscopy employs highly technical equipment, and the surgeon needs special training in the technique. He should master in-depth knowledge of the use of optics, electrical principles, gas under pressure, and the physiologic changes that occur when carbon dioxide is placed in the abdominal cavity. Above all, the surgeon must adhere rigidly to guidelines for appropriate technique, and deviation will most assuredly result in complications and even death. General surgery application of laparoscopy followed a wealth of medical experience from gynecological laparoscopies, which declared the technique as safe, reduced hospital stay with little pain and disfigurement. Laparoscopic cholecystectomy started to enjoy ever increasing popularity. It retained the advantages of shorter hospital stay, more rapid return to normal activities, less pain, small incisions and less postoperative ileus compared with the traditional open cholecystectomy. Soon many procedures were done using this new technique in adults and children. Anesthesia for laparoscopy has been established with a broad usage of agents and techniques. General anesthesia using balanced anesthesia technique including intravenous induction agents like: thiopentone, propofol, etomidate, and inhalational agents like nitrous oxide, isoflurane, desflurane, has been reported. Variety of muscle relaxants including succinylcholine, mivacurium, atracurium, vecuronium aiming at rapid recovery and cardiovascular stability. Total intravenous anesthesia using agnets like propofol, midazolam and ketamine, alfentanil and vecuronium has been reported also for outpatient laparoscopy. Epidural anesthesia was considered as safe alternative to general anesthesia for outpatient laparoscopy without associated respiratory depression. As for pain relief, many methods have been used. The pain mechanism is variable and analgesia requirement is less than those of open surgery. Cited complications include pneumothorax, cardiovascular collapse, surgical emphysema and pneumo-peritoneum complications. Among the implication for anesthesia care, the importance of preoperative monitoring, careful positioning and observation during the insufflation of carbon dioxide. The drive to have short term admission to hospital would make it imperative to use short acting rapidly eliminated anesthetic drugs, avoidance of vomiting and pain by proper use of modern anti-emetics and NSAID to help in avoidance of narcotics or reduction of the requirement.