Genome-wide DNA methylation profiles of autism spectrum disorder.
We aimed to identify differentially methylated genes and related signaling pathways in autism spectrum disorder (ASD). First, the DNA methylation profile in the brain samples (GSE131706 and GSE80017) and peripheral blood samples (GSE109905) was downloaded from the Gene Expression Omnibus database (GEO) dataset, followed by identification of differentially methylated genes and functional analysis. Second, the GSE109905 data set was used to further validate the methylation state and test the ability to diagnose disease of identified differentially methylated genes. Third, expression measurement of selected differentially methylated genes was performed in whole blood from an independent sample. Finally, protein-protein interaction (PPI) network of core differentially methylated genes was constructed. Totally, 74 differentially methylated genes were identified in ASD, including 38 hypermethylated genes and 36 hypomethylated genes. 15 differentially methylated genes were further identified after validation in the GSE109905 data set. Among these, major histocompatibility complex (HLA)-DQA1 was involved in the molecular function of myosin heavy chain class II receptor activity; HLA-DRB5 was involved in the signaling pathways of cell adhesion molecules, Epstein-Barr virus infection and antigen processing and presentation. In the PPI analysis, the interaction pairs of HLA-DQA1 and HLA-DRB5, FMN2 and ACTR3, and CALCOCO2 and BAZ2B were identified. Interestingly, FMN2, BAZ2B, HLA-DRB5, CALCOCO2 and DUSP22 had a potential diagnostic value for patients with ASD. The expression result of four differentially methylated genes (HLA-DRB5, NTM, IL16 and COL5A3) in the independent sample was consistent with the integrated analysis. Identified differentially methylated genes and enriched signaling pathway could be associated with ASD.


Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications.
Rifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)-detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC). We conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy. Among 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1-100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5-72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively. In this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.


Ninety-nine de novo assembled genomes from the moose (Alces alces) rumen microbiome provide new insights into microbial plant biomass degradation.
The moose (Alces alces) is a ruminant that harvests energy from fiber-rich lignocellulose material through carbohydrate-active enzymes (CAZymes) produced by its rumen microbes. We applied shotgun metagenomics to rumen contents from six moose to obtain insights into this microbiome. Following binning, 99 metagenome-assembled genomes (MAGs) belonging to 11 prokaryotic phyla were reconstructed and characterized based on phylogeny and CAZyme profile. The taxonomy of these MAGs reflected the overall composition of the metagenome, with dominance of the phyla Bacteroidetes and Firmicutes. Unlike in other ruminants, Spirochaetes constituted a significant proportion of the community and our analyses indicate that the corresponding strains are primarily pectin digesters. Pectin-degrading genes were also common in MAGs of Ruminococcus, Fibrobacteres and Bacteroidetes and were overall overrepresented in the moose microbiome compared with other ruminants. Phylogenomic analyses revealed several clades within the Bacteriodetes without previously characterized genomes. Several of these MAGs encoded a large numbers of dockerins, a module usually associated with cellulosomes. The Bacteroidetes dockerins were often linked to CAZymes and sometimes encoded inside polysaccharide utilization loci, which has never been reported before. The almost 100 CAZyme-annotated genomes reconstructed in this study provide an in-depth view of an efficient lignocellulose-degrading microbiome and prospects for developing enzyme technology for biorefineries.


Intraoperative transoesophageal echocardiography in a low birth weight neonate with atrioventricular septal defect.
An 18-day-old male neonate (45 cm, 1.8 kg) with a history of cyanosis and congestive heart failure from an atrioventricular septal defect (AVSD) with a large left-to-right shunt was scheduled for surgical repair of the AVSD. After routine induction of anaesthesia with fentanyl and vecuronium, a 4.5-mm diameter transoesophageal echocardiography (TOE) probe was inserted into the oesophagus, and systematic echocardiographic evaluation was performed during surgery. After cardiopulmonary bypass was stopped, intraoperative TOE revealed mild residual mitral valve regurgitation. Because good left ventricular wall motion was confirmed and haemodynamic parameters were stable, cardiopulmonary bypass was not reinitiated. The patient's cardiac output was low in the postoperative intensive care unit. TOE was performed the next day to detect the source of this problem, revealed severe regurgitation compared with that observed intraoperatively. TOE was useful for evaluation of the residual mitral valve regurgitation, and we reconfirmed the importance of continuous monitoring even in a low birthweight neonate undergoing repair of a complete AVSD.


Initial programmatic implementation of WHO option B in Botswana associated with increased projected MTCT.
: Botswana was one of the first African countries to transition from WHO Option A to Option B for prevention of mother-to-child HIV transmission (MTCT). We evaluated the impact of this transition on projected MTCT risk through review of 10,681 obstetric records of HIV-infected women delivering at 6 maternity wards. Compared with Option A, women receiving antenatal care under Option B were more likely to receive combination antiretroviral therapy (ART), adjusted odds ratio (aOR): 2.59 (95% confidence interval: 2.25 to 2.98), but they were also more likely to receive no antenatal antiretrovirals, aOR: 2.10 (95% confidence interval: 1.74 to 2.53). Consequently, initial implementation of Option B was associated with increased projected MTCT at 6 months of age, 3.79% under Option A and 4.69% under Option B (P < 0.001). Successful implementation of Option B or B+ may require that ART can be initiated within antenatal clinics, and novel strategies to remove barriers to rapid ART initiation.


COVID19 associated mucormycosis: A review.
Mucormycosis, a rare fungal disease has emerged as a new epidemic in India, during the CoronaVirus Disease 2019 (COVID-19) pandemic. Mucormycosis is caused by the mucormycetes group of molds. Immunocompromised states such as diabetes, chronic steroid use, and patients receiving immunosuppressant drugs are the risk factors for mucormycosis. The second wave of the COVID-19 pandemic has also invited the notorious mucormycosis in the current scenario. India has announced mucormycosis as a notifiable disease in May 2021, as the number of COVID-19-associated mucormycosis cases has increased swiftly. There are different opinions and evidence for the emergence of mucormycosis or the so-called 'black fungus'. It is proposed that the use of steroids, monoclonal antibodies, and prolonged hospitalization in the treatment of COVID-19 has substantially decreased the immunity in COVID-19-affected patients and maybe the reason for the emergence of fungal infections. The other hypothesis is that improper disinfection procedures such as using non-sterile water for humidification of oxygen can be the reason. Or, the COVID-19 infection itself produces an immunocompromised and diabetic-like state is again a question. This review mainly focuses on the discussion and identification of the most common risk factor for mucormycosis, investigations, and management of mucormycosis.


Fire alarms and oestrus in rats.
Vaginal smear cyclicity was used as a physiological test to compare the response of rats to the new "silent" fire alarm developed by the Laboratory Animals Centre with a conventional fire bell. The fire bell had a highly significant effect on the vaginal smear cyclicity whereas the rats exposed to the "silent" fire alarm showed no significant changes from the control animals in quiet conditions.


Influence of learning to read and write on the morphology of the corpus callosum.
Variations in the individual anatomy of the corpus callosum have been reported in several conditions. There seem to be genetic influencing factors, but it is impossible to rule out some environmental ones. This study focuses on the question of the environmental factors, using formal learning to read and write as the main difference in the groups to be compared. Based on magnetic resonance imaging sagital images, the contour of the corpus callosum (CC) of 41 carefully selected women (18 illiterate and 23 literate) was digitized. The comparison between the two groups showed a small difference in the region of the CC where parietal fibres are thought to cross. This region is thinner in illiterate subjects. As illiteracy in this group is the result of social constraints, and the two groups that were compared are well matched for other cultural and pragmatic aspects than literacy, the results are interpreted as showing the possible influence of formal learning to read and write, on the biological development of the brain.


Compartmentalized expression of two structurally and functionally distinct 4-coumarate:CoA ligase genes in aspen (Populus tremuloides).
4-Coumarate:CoA ligases (4CLs, EC 18.104.22.168) are a group of enzymes necessary for maintaining a continuous metabolic flux for the biosynthesis of plant phenylpropanoids, such as lignin and flavonoids, that are essential to the survival of plants. So far, various biochemical and molecular studies of plant 4CLs seem to suggest that 4CL isoforms in plants are functionally indistinguishable in mediating the biosynthesis of these phenolics. However, we have discovered two functionally and structurally distinct 4CL genes, Pt4CL1 and Pt4CL2 (63% protein sequence identity), that are differentially expressed in aspen (Populus tremuloides). The Escherichia coli-expressed and purified Pt4CL1 and Pt4CL2 proteins exhibited highly divergent substrate preference as well as specificity that reveal the association of Pt4CL1 with the biosynthesis of guaiacyl-syringyl lignin and the involvement of Pt4CL2 with other phenylpropanoid formation. Northern hybridization analysis demonstrated that Pt4CL1 mRNA is specifically expressed in lignifying xylem tissues and Pt4CL2 mRNA is specifically expressed in epidermal layers in the stem and the leaf, consistent with the promoter activities of Pt4CL1 and Pt4CL2 genes based on the heterologous promoter-beta-glucouronidase fusion analysis. Thus, the expression of Pt4CL1 and Pt4CL2 genes is compartmentalized to regulate the differential formation of phenylpropanoids that confer different physiological functions in aspen; Pt4CL1 is devoted to lignin biosynthesis in developing xylem tissues, whereas Pt4CL2 is involved in the biosynthesis of other phenolics, such as flavonoids, in epidermal cells.


Ultrasound for postoperative surveillance after mastectomy in patients with breast cancer: A retrospective study.
This study aimed to evaluate the clinical usefulness of postoperative surveillance by ultrasound (PSU) in patients after breast cancer surgery.In this retrospective study, 324 patients with breast cancer after mastectomy were included between January 2006 and December 2008. The final-positive lesions (FPL) were diagnosed according to the results of cytopathology, clinical and imaging examinations. The outcome evaluations included the sensitivity (SS), specificity (SC), ultrasound accuracy for FPL (UAFPL), and positive predictive value (PPV) after the mastectomy.A total of 5117 ultrasound examinations were conducted for all those patients to the December 2016. After mastectomy, the SS, SC, UAFPL, and PPV were as follows: mastectomy bed (SS, 100.0%; SC, 99.7%; UAFPL, 99.7%; and PPV, 36.0%), contralateral breast (SS, 100.0%; SC, 99.0%; UAFPL, 99.0%; and PPV, 25.4%), ipsilateral axillary or supraclavicular (SS, 91.7%; SC, 99.4%; UAFPL, 99.4%; and PPV, 25.6%), and contralateral axilla or supraclavicular lymph nodes (SS, 100.0%; SC, 99.9%; UAFPL, 99.9%; and PPV, 33.3%).In summary, we demonstrated that applied PSU can detect the malignant lesions in the breast regional area with high sensitivity, specificity and accuracy.


Highly Stereoselective Biocatalytic Synthesis of Key Cyclopropane Intermediate to Ticagrelor.
Extending the scope of biocatalysis to important non-natural reactions such as olefin cyclopropanation will open new opportunities for replacing multi-step chemical syntheses of pharmaceutical intermediates with efficient, clean, and highly selective enzyme-catalyzed processes. In this work, we engineered the truncated globin of Bacillus subtilis for the synthesis of a cyclopropane precursor to the antithrombotic agent ticagrelor. The engineered enzyme catalyzes the cyclopropanation of 3,4-difluorostyrene with ethyl diazoacetate on a preparative scale to give ethyl-(1R, 2R)-2-(3,4-difluorophenyl)-cyclopropanecarboxylate in 79% yield, with very high diastereoselectivity (>99% dr) and enantioselectivity (98% ee), enabling a single-step biocatalytic route to this pharmaceutical intermediate.


Hormonally regulated proteins in cultured human fetal lung: analysis by two-dimensional gel electrophoresis.
We used high-resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) to identify hormonally regulated proteins in cultured human fetal lung. Proteins labeled with [35S]methionine were separated by 2-D PAGE, and fluorograms were analyzed by computer-assisted analysis of densitometric scans. Dexamethasone (10 nM) and gamma-interferon (10 ng/ml) induced (2- to 22-fold vs. control) distinct sets of proteins (comprising approximately 2% of approximately 1,000 resolved proteins). Treatment with forskolin (10 microM) plus 3-isobutyl-1-methylxanthine (IBMX, 100 microM), which increases intracellular adenosine 3',5'-cyclic monophosphate (cAMP), induced both unique proteins and several proteins induced by dexamethasone. One protein (Mr 40,000, pI 4.4) was induced only with combined dexamethasone and cAMP treatment. Dexamethasone repressed four proteins, but inhibition was not observed with other hormones. Some of the regulated proteins were enriched in either fibroblasts or type II cells isolated from lung explants. We found no proteins that were consistently regulated by triiodothyronine (T3) (2 nM) or transforming growth factor-beta (10 ng/ml). Additionally, none of the hormonal treatments substantially altered the rate of methionine incorporation into total protein. Thus we have identified separate subsets of proteins that are regulated by glucocorticoids, gamma-interferon, and cAMP; these proteins may be important mediators of hormonal effects in the developing fetal lung.


Microprinted tumor spheroids enable anti-cancer drug screening.
Spheroids present a biologically relevant model of avascular tumors and a unique tool for discovery of anti-cancer drugs. Despite being used in research laboratories for several decades, spheroids are not routinely used for drug discovery primarily due to the difficulty of mass-producing uniformly-sized spheroids and intense labor involved in handling, drug treatment, and analyzing them. We overcome this barrier using a novel technology to robotically microprint spheroids in standard 384-well plates. An aqueous drop containing cancer cells is dispensed into a bath of a second, immiscible aqueous phase. The drop maintains cells in close proximity to aggregate into a single spheroid. Using U-87 MG brain cancer cells, we show that this approach produces spheroids of well-defined size with ~10% deviation from their mean diameter. We demonstrate the feasibility of robotic, high throughput compound screening against tumor spheroids using a collection of 25 standard chemotherapeutics and molecular inhibitors against U-87 MG spheroids. Each drug is used in a wide range of concentrations. Viability of cancer cells in drug-treated spheroids is measured using a PrestoBlue assay. Morphological changes are used as a secondary measure for analysis of drug effect. We identify several compounds that effectively inhibit growth of spheroids. To generate a scoring system for effectiveness of drugs, we use half-maximum inhibitory concentration (IC50), maximum inhibition (Emax), and area under the dose-response curve (AUC) to present a multi-parametric approach that takes into account both potency and efficacy of drugs. Our robotic technology offers a low cost and convenient platform for screening large collections of chemical compounds against realistic tumor models prior to expensive and tedious in vivo tests, dramatically improving testing throughput and efficiency, and reducing costs.


Phycoerythrin Peptide from Pyropia yezoensis Alleviates Endoplasmic Reticulum Stress Caused by Perfluorooctane Sulfonate-Induced Calcium Dysregulation.
Perfluorooctane sulfonate (PFOS), a stable fluorosurfactant, causes endoplasmic reticulum (ER) stress in the brain. This study was designed to investigate whether a phycoerythrin-derived peptide of Pyropia yezoensis (PYP) reduces PFOS-induced ER stress associated with calcium dysregulation. The protective effects of PYP were determined by cell viability, immunoblotting for ER stress response protein glucose-regulated protein 78 (GRP78) and calcium-dependent protein kinases in rat frontal cortical neurons. PFOS-induced decrease in cell viability was attenuated by PYP pretreatment (1 µg/mL) for 24 h, which was downregulated by inhibiting tropomyosin-receptor kinase B (TrkB). PYP pretreatment downregulated the increase in intracellular calcium levels and phosphorylation of calcium/calmodulin-dependent protein kinase II and c-Jun N-terminal kinase which are associated with a PFOS-induced increase in GRP78. The PFOS-induced increase in GRP78 was downregulated via activation of TrkB receptor-linked extracellular signal-regulated kinases 1/2 (ERK1/2) by PYP pretreatment. Moreover, PYP microinjections (1 µg/kg, 0.54 nmol) attenuated the GRP78 expression in rat prefrontal cortex caused by PFOS (10 mg/kg) exposure for 2 weeks. These findings demonstrate that PYP enhances frontal cortical neuron viability via activation of TrkB receptor-ERK1/2 signaling and attenuation of ER stress in rat prefrontal cortex against PFOS exposure, suggesting that PYP might prevent neuronal dysfunctions caused by PFOS-induced ER stress.


Effect of blood sampling schedules on protein drug binding in the rat.
The effect of repetitive blood sampling schedules on the plasma protein binding of a highly protein-bound drug, dicumarol, was investigated in the rat. Blood samples were withdrawn at pre-determined intervals and hematocrit, total plasma protein, plasma albumin and free fatty acids were measured. Plasma protein binding of [14C]dicumarol was assessed by equilibrium dialysis. Withdrawal of 1 ml of blood every hour for 12 hr produced a significant decrease at 2 hr in hematocrit (42%), total plasma protein (14.5%), plasma albumin (31.4%) and an increase in free fatty acids (238%) compared to the control (O time) levels. The free fraction of dicumarol in the plasma increased 1350%, from 0.38 to 5.13%. Sampling schedules involving blood withdrawal of 0.5 mg/2 hr and 1 ml/2 hr producing less dramatic changes, but in all cases the free fraction of dicumarol was elevated at the 12-hr time period. An inverse relationship was found between plasma albumin concentrations and dicumarol-free fraction. The blood sampling schedule was found to alter the pharmacological response (prothrombin time) and pharmacokinetics of dicumarol after an 8 mg/kg i.v. dose. These results illustrate the influence multiple blood sampling can exert on pharmacodynamic parameters in studies involving small laboratory animals and highly protein-bound drugs.


Prognostic scores and biomarkers for pediatric community-acquired pneumonia: how far have we come?
This article aimed to review the current prognostic and diagnostic tools used for community-acquired pneumonia (CAP) and highlight those potentially applicable in children with CAP. Several scoring systems have been developed to predict CAP mortality risk and serve as guides for admission into the intensive care unit. Over the years, clinicians have adopted these tools for improving site-of-care decisions because of high mortality rates in the extremes of age. The major scoring systems designed for geriatric patients include the Pneumonia Severity Index and the confusion, uremia, respiratory rate, blood pressure, age >65 years (CURB-65) rule, as well as better predictors of intensive care unit admission, such as the systolic blood pressure, multilobar chest radiography involvement, albumin level, respiratory rate, tachycardia, confusion, oxygenation and arterial pH (SMART-COP) score, the Infectious Diseases Society of America/American Thoracic Society guidelines, the criteria developed by España et al as well as the systolic blood pressure, oxygenation, age and respiratory rate (SOAR) criteria. Only the modified predisposition, insult, response and organ dysfunction (PIRO) score has so far been applied to children with CAP. Because none of the tools is without its limitations, there has been a paradigm shift to incorporate biomarkers because they are reliable diagnostic tools and good predictors of disease severity and outcome, irrespective of age group. Despite the initial preponderance of reports on their utility in geriatric CAP, much progress has now been made in demonstrating their usefulness in pediatric CAP.


Spin-polarized transport in hydrogen-passivated graphene and silicene nanoribbons with magnetic transition-metal substituents.
We present a systematic theoretical study of the electronic transport in hydrogen passivated zigzag graphene and silicene nanoribbons with between zero and four neighboring H atoms on one edge replaced by magnetic transition metals (Fe, Co, and Ni). The calculations were performed using equilibrium transport and density-functional theory with the generalized gradient approximation to exchange and correlation. We considered the magnetic moments of the two edges aligned both ferromagnetically (Ferro-F form) and antiferromagnetically (Ferro-A form). The Ferro-A graphene-based ribbons were all semiconducting and would support moderate spin-polarized currents of either sign by applying positive or negative gate voltages. The Ferro-F graphene-based ribbons were all metallic; the most interesting for possible spintronic applications being that with a single Ni atom, in which strong spin-filtering at low bias resulted from a deep trough in the transmission of one spin component around the Fermi level. By contrast, in the Si-based analog this trough was split, partially eliminating the polarization of the current. This splitting was found to be related to the buckled structure of the Si-based nanoribbon, which has its origin in its preference for sp(3)-like hybridization.


The choice of opioid receptor subtype in isolated preparations by ohmefentanyl.
Ohmefentanyl has significant inhibitory actions on the electrically evoked contractions of guinea pig ileum and mouse vas deferens. Their IC50 values are 0.15 nM and 0.89 nM, respectively. In the guinea pig ileum and the mouse vas deferens, both mu-antagonist naloxone and (mu + kappa)-antagonist Mr. 2266 antagonize readily the agonist action of ohmefentanyl, indicating that ohmefentanyl acts on mu-receptors in the guinea pig ileum and the mouse vas deferens. Like other mu-agonists, ohmefentanyl has agonist activity but no antagonist action in the rat vas deferens. In the rabbit vas deferens, the activity of ohmefentanyl is very weak. The IC50 value is 149 nM. These results further indicate that ohmefentanyl is a potent and selective mu-agonist.


Glutaraldehyde modified red blood cells delivering artesunate to the liver as a dual therapeutic and prophylactic antimalaria strategy.
Malaria can spread quickly in the population and develop rapidly. Patients with malaria usually die due to lack of timely and effective treatment. Artesunate (AS) is a highly effective and low-toxicity antimalarial drug, but its short half-life in the blood makes it difficult to control the malaria infection completely. Red blood cells (RBCs) have great biodegradability and can be employed to encapsulate various drugs. In this work, we employed RBCs as carriers to encapsulate AS and modified them with glutaraldehyde to construct an intelligent response drug delivery system (G-AS-RBCs) targeting the liver for antimalaria therapeutic and prophylactic activity. The G-AS-RBCs had a drug loading amount of 6.56 ± 0.14 mg 10-8 cells, suggesting excellent biocompatibility. G-AS-RBCs exhibited strong liver targeting efforts and can be maintained in the mice for at least 9 days, showing the potential for malaria prevention. The enrichment of AS in the liver was enhanced because of the natural liver targeting of erythrocytes and the enhancement of liver targeting by glutaraldehyde treatment. Furthermore, AS entrapped into RBCs also showed improved slow-release characteristics and achieved a better effect of inhibiting or killing the malaria parasite than free drugs. Therefore, this RBC-based strategy is expected to realize the prevention and treatment of malaria and has good application prospects.


Homozygous mutation in the prokineticin-receptor2 gene (Val274Asp) presenting as reversible Kallmann syndrome and persistent oligozoospermia: case report.
Prokineticin 2 (Prok2) or prokineticin-receptor2 (Prok-R2) gene mutations are associated with Kallmann syndrome (KS). We describe a new homozygous mutation of Prok-R2 gene in a man displaying KS with an apparent reversal of hypogonadism. The proband, offspring of consanguineous parents, presented at age 19 years with absent puberty, no sense of smell, low testosterone and gonadotrophin levels. Magnetic resonance imaging showed olfactory bulb absence. The patient achieved virilization and spermatogenesis with gonadotrophin administration. Two years after discontinuing hormonal therapy, he maintained moderate oligozoospermia and normal testosterone levels. Prok2 and Prok-R2 gene sequence analyses were performed. The proband had a homozygous mutation in Prok-R2 exon 2 that harbours the c.T820>A base substitution, causing the introduction of an aspartic acid in place of valine at position 274 (Val274Asp). His mother had the same mutation in heterozygous state. This report describes a novel homozygous mutation of Prok-R2 gene in a man with variant KS, underlying the role of Prok-R2 gene in the olfactory and reproductive system development in humans. Present findings indicate that markedly delayed activation of gonadotrophin secretion may occur in some KS cases with definite gene defects, and that oligozoospermia might result from a variant form of reversible hypogonadotrophic hypogonadism.


Randomized effectiveness study of four therapeutic strategies for TMJ closed lock.
For individuals with temporomandibular joint (TMJ) disc displacement without reduction with limited mouth opening (closed lock), interventions vary from minimal treatment to surgery. In a single-blind trial, 106 individuals with TMJ closed lock were randomized among medical management, rehabilitation, arthroscopic surgery with post-operative rehabilitation, or arthroplasty with post-operative rehabilitation. Evaluations at baseline, 3, 6, 12, 18, 24, and 60 months used the Craniomandibular Index (CMI) and Symptom Severity Index (SSI) for jaw function and TMJ pain respectively. Using an intention-to-treat analysis, we observed no between-group difference at any follow-up for CMI (p > or = 0.33) or SSI (p > or = 0.08). Both outcomes showed within-group improvement (p < 0.0001) for all groups. The findings of this study suggest that primary treatment for individuals with TMJ closed lock should consist of medical management or rehabilitation. The use of this approach will avoid unnecessary surgical procedures.


Efficacy and safety of once-weekly intravenous epoetin alfa in maintaining hemoglobin levels in hemodialysis patients.
Although an erythropoiesis-stimulating agent (ESA) is most frequently administered intravenously for treatment of anemia in patients with chronic kidney disease who are on dialysis, few studies have compared the efficacy of different intravenous (i.v.) dosing schedules. This multicenter, phase IIIb, open-label, controlled study randomized 289 stable hemodialysis patients to continue with conventional dosing of i.v. epoetin alfa or darbepoetin, or to switch to once-weekly i.v. epoetin alfa at the same cumulative weekly starting dose, to maintain hemoglobin levels at 11.0-13.0 g/dL, and within 1.0 g/dL of the baseline value. Hemoglobin levels and ESA doses were recorded every 4 weeks for 28 weeks. Hemoglobin levels fell significantly and ESA doses increased significantly between baseline and week 28 (mean of week 16-28 values) in the once-weekly epoetin alfa group, compared with the conventional treatment group (p< 0.001). The adjusted difference in mean hemoglobin levels between the groups was 0.73 g/dL (greater than the threshold for therapeutic equivalence of 0.5 g/dL). The changes between groups from baseline was significant at all time points for hemoglobin levels (0.36, 0.46, 0.81, 0.87, 0.78, 0.62 and 0.49 g/dL) and from week 12 for ESA dose (718.5, 1,326.5, 1,732.0, 1,839.7 and 1,959.1 IU/week; p=0.005). Hemoglobin was maintained at the target level in 78% and 84% of patients on conventional dosing, and 67% and 64% of those on once-weekly epoetin alfa in the intention-to-treat (p=0.1) and per protocol (p=0.016) populations, respectively. This study did not show therapeutic equivalence of once-weekly i.v. epoetin alfa with conventional dosing regimens.


Scrap tyre pyrolysis: Modified chemical percolation devolatilization (M-CPD) to describe the influence of pyrolysis conditions on product yields.
This paper attempts to develop a modified chemical percolation devolatilization (M-CPD) model that can include heat transfer, primary pyrolysis and the secondary cracking reactions of volatiles together to describe the pyrolysis of waste scrap tyre chip, as well as to examine the influence of operating conditions on the scrap tyre pyrolysis product yields. Such a study has yet to be conducted in the past, thereby leading to a large knowledge gap failing to understand the pyrolysis of the coarse feedstock appropriately. To validate the developed model, a number of operating parameters including reactor configurations, carrier gas compositions (argon and argon blended with CO2 and/or steam), scrap tyre chip size (0.5-15.0 mm), terminal pyrolysis temperature (400-800 °C) and heating rate (10 °C/min and 110 °C/min) were examined in a lab-scale fixed-bed pyrolyser, with a particular focus on the secondary cracking extents of the liquid tar. Through both experimental investigation and modelling approach, it was found that significant secondary cracking extent occurred upon the increase in the feedstock size, heating rate and residence time. Upon the fast pyrolysis, the average temperature gap between the centres of the coarse particle and reactor wall could reach a maximum of 115 °C for the tyre chips of 6-15 mm. Consequently, its primary volatiles underwent the secondary cracking reaction at an overall extent of 17% at a terminal temperature of 600 °C and a fast heating rate of 110 °C/min. Consequently, the yield of light gases including methane was increased remarkably. The flow rate of inert carrier gas was also influential in the secondary cracking, in which a maximum tar yield (54 wt%) was reached at a carrier gas flow rate of 1.5 L/min. This indicates the occurrence of secondary cracking has been largely minimised. At a pyrolysis temperature of 600 °C, the addition of CO2 in the carrier gas had an insignificant effect on the product yield distribution under the slow heating scheme. In contrast, the addition of steam resulted in a slight increase of carbon monoxide, presumably due to the occurrence of gasification reaction.


Enduracidin analogues with altered halogenation patterns produced by genetically engineered strains of Streptomyces fungicidicus.
Enduracidins (1, 2) and ramoplanin (3) are structurally and functionally closely related lipodepsipeptide antibiotics. They are active against multi-drug-resistant Gram-positive pathogens, including MRSA. Each peptide contains one chlorinated non-proteinogenic amino acid residue, Cl(2)-Hpg or Cl-Hpg. To investigate the timing of halogenation and the importance of chlorination on bioactivity and bioavailability of enduracidin, and to probe the substrate specificity and portability of the ramoplanin halogenase, we constructed the mutant strain SfDelta30 in which the enduracidin halogenase gene orf30 had been deleted and complemented it with the ramoplanin counterpart orf20. We also expressed orf20 in the enduracidin wild-type producer. Metabolite analysis revealed SfDelta30 produced the novel analogues dideschloroenduracidins A (4) and B (5), while the recombinant strains SfDelta30R20 and SfR20 produced monodeschloroenduracidins A (6) and B (7) and a trichlorinated enduracidin (8), respectively. In addition, orf30 self-complementation yielded the strain SfDelta30E30, which is capable of producing six peptides including 6 and 7. MS/MS analysis positioned the single chlorine atom in 6 at Hpg(13) and localized the third chlorine atom in 8 to Hpg(11). Biological evaluation of these enduracidin analogues indicated that all retained activity against Staphylococcus aureus. Our findings lay the foundation for further utilization of enduracidin and ramoplanin halogenases in combinatorial biosynthesis.


Treatment of Dowling-Degos disease with fractional Er:YAG laser.
Dowling-Degos disease (DDD) is a rare, benign, autosomal dominant disorder characterized by reticulated pigmentation on flexural areas. Recently, a report of successful Er:YAG ablative laser treatment without any adverse effects was issued. A 49-year-old Korean woman presented with numerous small, hyperpigmented macules in a reticular pattern on her face, axillae, and inguinal folds of several years duration. Histologic examination revealed acanthosis with thin elongated rete ridges, basal branching, and widening. She was diagnosed as having DDD and was treated successfully without any adverse effects using a fractional 2,940-nm Er:YAG ablative laser (LOTUSII, Laseroptek, Sungnam, Korea). Er:YAG ablative laser treatment could be an effective treatment modality for DDD, but in Asians, who have darker skins than Caucasians, or in patients with skin lesions on the face, post-inflammatory hyperpigmentation could be problematic after treatment. Fractional Er:YAG ablative laser treatment should be viewed as an alternative therapeutic option for DDD.


Color blindness defect and medical laboratory technologists: unnoticed problems and the care for screening.
Color-blindness is the inability to perceive differences between some color that other people can distinguish. Using a literature search, the results indicate the prevalence of color vision deficiency in the medical profession and its on medical skills. Medical laboratory technicians and technologists employees should also screen for color blindness. This research aimed to study color blindness prevalence among Hospitals' Clinical Laboratories' Employees and Students in Tehran University of Medical Sciences (TUMS). A cross-sectional descriptive and analytical study was conducted among 633 TUMS Clinical Laboratory Sciences' Students and Hospitals' Clinical Laboratories' Employees to detect color-blindness problems by Ishihara Test. The tests were first screened with certain pictures, then compared to the Ishihara criteria to be possible color defective were tested further with other plates to determine color - blindness defects. The data was saved using with SPSS software and analyzed by statistical methods. This is the first study to determine the prevalence of color - blindness in Clinical Laboratory Sciences' Students and Employees. 2.4% of TUMS Medical Laboratory Sciences Students and Hospitals' Clinical Laboratories' Employees are color-blind. There is significant correlation between color-blindness and sex and age. But the results showed that there is not significant correlation between color-blindness defect and exposure to chemical agents, type of job, trauma and surgery history, history of familial defect and race. It would be a wide range of difficulties by color blinded students and employees in their practice of laboratory diagnosis and techniques with a potentially of errors. We suggest color blindness as a medical conditions should restrict employment choices for medical laboratory technicians and technologists job in Iran.


Ultrastructural studies of the nucleoli in diploid and trisomic chickens.
Chickens having a trisomic complement for the nucleolar organizer region (NOR) serve as a model for investigations on gene expression, molecular regulation, and physiological alterations resulting from extra genetic material. Of fundamental importance is the question of whether the extra set of ribosomal cistrons in trisomic chickens generates a morphologically and biochemically complete nucleolus. Ultrastructural and cytochemical studies of diploid and trisomic embryonic and adult cells were undertaken. All structures identified in trisomic cells as nucleoli by gross morphology were shown to be RNA rich by acridine orange fluorescence. At the ultrastructural level, the expected granular and fibrillar components were identified in all nucleoli of trisomic cells. Fibrillar centers, indicative of NOR's, were seen in all cases. These and other results from silver staining suggest full gene activity for each of the three chromosomes in the trisomic cell at all stages of development.


The role of peroxisomes in glycerol ether lipid metabolism.
Peroxisomes (microbodies) are ubiquitous subcellular organelles whose functions in cellular metabolism are not clear. In recent years peroxisomes have been shown to play roles in the oxidation of long chain fatty acids and ether lipid biosynthesis. The key enzymes of the acyl DHAP pathway i.e. DHAP acyltransferase and alkyl DHAP synthase have been shown to be localized in peroxisomes indicating that these organelles are obligatory for the biosynthesis of cellular glycerol ether lipids. This is proved by the discovery that in the tissues of patients suffering from Zellweger cerebrohepatorenal syndrome, an autosomal recessive disorder where peroxisomes are known to be absent, the acyl DHAP pathway enzymes and the ether lipids were also found to be deficient. Based on such biochemical abnormalities a number of similar genetic disorders such as neonatal adrenoleukodystrophy, different forms of chondrodysplasia punctata, infantile Refsum disease etc. have been characterized as peroxisomal deficiency disorders. These and other findings show that peroxisomes have a regulatory role in membrane lipid biogenesis. It seems that the main role of peroxisomes is to compartmentalize biochemical reactions which cannot proceed in other cellular organelles either due to formation of toxic product (H2O2) or due to non-availability of crucial metabolite (DHAP). The products of the reactions catalyzed by the peroxisomal enzymes e.g. acetyl CoA or alkyl DHAP are then transported out from peroxisomes to other cellular compartments where they are utilized to produce fatty acids, cholesterol, glycerol ether lipids etc. for membrane biogenesis.


Prophylactic effect of low doses of human leukocyte interferon against infection with rhinovirus.
The prophylactic effect of low doses of human leukocyte interferon (HuIFN-alpha) against infection with rhinovirus was measured in double-blind, placebo-controlled studies with volunteer subjects. An antihistamine (chlorpheniramine) was given before administration of single or multiple doses of HuIFN-alpha but saturated cotton pledget or by aerosol; volunteers were then challenged with rhinovirus. When the results for all groups were combined, a lower frequency of respiratory illness was demonstrated in the HuIFN-alpha-treated volunteers (20 of 39 vs. 11 of 38, P less than 0.05). A significant improvement in mean symptom scores was found only in the volunteers who received HuIFN-alpha by cotton pledget. The total numbers of isolates of rhinovirus and seroconversions were similar for HuIFN-alpha-treated and control volunteers. No significant side effects were noted in the HuIFN-alpha-treated volunteers. Higher concentrations or improved methods of delivery of HuIFN-alpha will be necessary for improving the clinical efficacy of HuIFN-alpha against viral infections in the respiratory system.


Design and material evaluation for a novel lumbar disc replacement implanted via unilateral transforaminal approach.
The degeneration of the intervertebral disc is one of the principal causes of low back pain. Total disc replacement is a surgical treatment that aims to replace the degenerated disc with a dynamic implant to restore spine biomechanics. This paper proposes the first design of an elastomeric lumbar disc replacement that is implanted as a pair of devices via unilateral transforaminal surgical approach. Furthermore, several biomaterials (Polyurethanes (PU) and Polycarbonate Urethanes (PCU)) are evaluated for the purpose of the implant to mimic the axial compliance of the spine. Bionate II 80A (a pure PCU), Elast Eon 82A E5-325 (a PU with polydimethylsiloxane and polyhexamethylene oxide), Chronosil (a PCU based silicone elastomer) 80A with 5% and 10% of silicone were obtained and injection moulded according to the shape of the implant core, which was defined after a stress distribution analysis with the finite element method. The dimensions for each specimen were: 14.6 × 5.6 × 6.1 mm (length, width and height). Quasistatic compression tests were performed at a displacement rate of 0.02 mm/s. The obtained stiffness for each material at 1 mm displacement was: Bionate II 80A, 448.48 N/mm; Elast Eon 82A E5-325, 216.55 N/mm; Chronosil 80A 5%, 127.73 N/mm; and Chronosil 80A 10%, 126.48 N/mm. Dimensional changes were quantified after two quasi-static compression tests. Plastic deformation was perceived in all cases with a total percentage of height loss of: 4.1 ± 0.5% for Elast Eon 82A E5-325; 3.2 ± 0.5% for Chronosil 80A 10%; 2.7 ± 0.3% for Chronosil 80A 5% and 1.1 ± 0.2% for Bionate II 80A. The mechanical behaviour of these biomaterials is discussed to assess their suitability for the novel disc replacement device proposed.


Hydroxy Chalcones and Analogs with Chemopreventive Properties.
The aim of this review is to highlight the chemopreventive properties of hydroxy-substituted natural and synthetic chalcones along with a number of their analogs. These products display various biological activities, and have many applications against various diseases. Antioxidant and anti-inflammatory properties of chalcones bearing hydroxy substituents are underlined. The influence of hydroxy substituents located on ring A, B, or both are systematized according to the exhibited biological properties.


Validation of the quality of The National Pain Database for pain management services in the United Kingdom.
Data on specialist pain management is scarce. We evaluated PainDB, a database which aggregates this information from UK pain clinics. PainDB entries for 1120 patients (2648 consultations) were compared to records at 30 pain clinics. Staff were surveyed about normal practice at 28 sites. First consultations (17 135) on the aggregated PainDB were analysed for 2003 for omissions. Those consultations included on PainDB (54.6%) showed good concurrence with written notes (88.1%), with no pattern for the missing visits. Questionnaire responses were often absent from notes (56%) and diagnosis was most frequently omitted from PainDB (12.4-18.4%). Clinic staff overestimated completeness. Despite commitment, PainDB is currently unsuitable for research or audit. As routine hospital data should provide information on activity, specific questions on severity and outcome could be answered by short-term recording of predefined variables.


Modulation of chromosome damage localization by DNA replication timing.
Non-random occurrence of induced chromosome breakpoints (BP) has been repeatedly reported. DNA synthesis and chromatin remodeling may influence chromosome BP localization. The CHO9 X chromosome exhibits an early replicating short euchromatic arm (Xpe) and a late replicating long heterochromatic arm (Xqh). We investigated the role played by DNA replication and related chromatin remodeling processes on BP distribution in eu/heterochromatin using the CHO9 X chromosome as a model. BP induced by etoposide, a topoisomerase II inhibitor, as well as by the S-dependent clastogens ultraviolet-C light (UV-C) and methyl methanesulfonate (MMS) were mapped to CHO9 X chromosome arms. The base analogue 5-bromo-2'-deoxyuridine (BrdUrd) was pulse-added immediately after UV-C irradiation or during etoposide and MMS treatments (40 min) to identify cells in early S-phase (Xpe labeled) or late S-phase (Xqh labeled) after indirect BrdUrd immunodetection in metaphase spreads using primary anti-BrdUrd and secondary fluorochrome-tagged antibodies. During early S-phase, BP induced by etoposide and MMS mapped preferentially to Xpe while BP produced by UV-C localized randomly. BP induced by all agents during late S-phase clustered in Xqh. Results obtained suggest that replication time of eu/heterochromatin as well as chromatin remodeling may determine BP localization on the CHO9 X chromosome.


[Application of a calling and queuing system in blood sampling in the clinical laboratory].
This paper introduces the application of a calling and queuing system for blood sample collection in a large hospital in China. Besides the basic function, it has following functions. (a) A real name system: get the number according to the laboratory application form to prevent the phenomena of buying a number and an empty number. (b) Two times waiting: the patient should wait at the main hall, then at the blood sampling window so as to improve the work efficiency. (c) The flowchart for an outpatient blood testing is as following: getting the number --> waiting --> blood sampling --> getting the test information report. This system is capable of not only optimizing the work flow, but also improving the clinical environment. It shortens the patient's waiting time and raises the laboratory quality as well.


Bypass of Abasic Site-Peptide Cross-Links by Human Repair and Translesion DNA Polymerases.
DNA-protein cross-links remain the least-studied type of DNA damage. Recently, their repair was shown to involve proteolysis; however, the fate of the peptide remnant attached to DNA is unclear. Particularly, peptide cross-links could interfere with DNA polymerases. Apurinuic/apyrimidinic (AP) sites, abundant and spontaneously arising DNA lesions, readily form cross-links with proteins. Their degradation products (AP site-peptide cross-links, APPXLs) are non-instructive and should be even more problematic for polymerases. Here, we address the ability of human DNA polymerases involved in DNA repair and translesion synthesis (POLβ, POLλ, POLη, POLκ and PrimPOL) to carry out synthesis on templates containing AP sites cross-linked to the N-terminus of a 10-mer peptide (APPXL-I) or to an internal lysine of a 23-mer peptide (APPXL-Y). Generally, APPXLs strongly blocked processive DNA synthesis. The blocking properties of APPXL-I were comparable with those of an AP site, while APPXL-Y constituted a much stronger obstruction. POLη and POLκ demonstrated the highest bypass ability. DNA polymerases mostly used dNTP-stabilized template misalignment to incorporate nucleotides when encountering an APPXL. We conclude that APPXLs are likely highly cytotoxic and mutagenic intermediates of AP site-protein cross-link repair and must be quickly eliminated before replication.


Preparation of thrombokinase from bovine plasma.
THROMBOKINASE IS PREPARED FROM BOVINE PLASMA BY A PROCEDURE INVOLVING: treatment with diatomaceous silica, adsorption on barium sulfate, flowing elution with two successive phosphate buffers, ammonium sulfate fractionation, "spontaneous" activation in concentrated solution, and isoelectric precipitation. The yield of nitrogen is 0.002 per cent, corresponding to 1.2 mg. protein per liter of plasma. When diluted back to the volume of parent plasma, and complemented by calcium plus cephalin, the product causes appreciable activation of prothrombin in 1 minute. Thus, the quantity of thrombokinase obtainable is compatible with a physiologic role. In the more complex system used for routine assay, thrombokinase can be supplied by crude plasma at a dilution of 1/500. In parallel tests, the product appears to be more active than its parent plasma, although it contains only 0.002 per cent of the nitrogen. However, the thrombokinase of the product has been activated, whereas the thrombokinase of the plasma is probably in an inactive precursor state. When diluted back to the volume of parent plasma, to a concentration of 0.2 microgram nitrogen per ml., thrombokinase can slowly activate prothrombin in the presence of oxalate, and without the addition of accessory factors. Activation of prothrombin in the presence of oxalate is faster with higher concentrations of thrombokinase.


Portal venous gas: is it a premorbid indicator?
A 72-year-old Caucasian man presented with subtle and insidious symptoms of pain in the left iliac fossa and vomiting. The first clinical impression was of diverticulitis but he did not improve with conservative management. An initial contrast tomography (CT) scan demonstrated no diagnostic features. Four days later, a repeat CT scan demonstrated intramural gas in the ascending colon and in the intrahepatic portal venous radicles. There was a thrombus in the superior mesenteric artery with infarction of the caecum and ascending colon. An urgent right hemicolectomy was carried out. Although there was resolution of the thrombus and air in the portal system, the patient died 8 days later from intestinal haemorrhage.


[Effect of isoflurane on spinal dorsal horn WDR neuronal activity in cats].
The effects of isoflurane (0.5% and 1.5%) on the spinal dorsal horn wide dynamic range (WDR) neuronal activity were studied in either spinal cord intact or spinal cord-transected cats. Extracellular activity was recorded in the dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli applied to the cutaneous receptive fields on the left hind foot pads of intact or decerebrate, spinal cord transected (L1-2) cats. When bradykinin (BK) 10 micrograms was injected into the femoral artery ipsilateral to the recording site as the noxious test stimulus in the spinal cat, all of 17 WDR neurons gave excitatory responses which were not depressed by 0.5% isoflurane but were depressed significantly by 1.5%. On the other hand, when the injection of BK 10 micrograms into the femoral artery ipsilateral to the recording site was used in the intact cat, 13 of 24 WDR neurons (54%) gave excitatory responses, which were significantly depressed by 0.5% and 1.5% isoflurane, and 11 of 24 WDR neurons (46%) gave inhibitory responses, which were significantly depressed by 0.5% and 1.5% isoflurane. We have found that isoflurane reduces the excitation as well as the inhibition of dorsal horn WDR neuronal activity induced by BK injection.


The intergenic small non-coding RNA ittA is required for optimal infectivity and tissue tropism in Borrelia burgdorferi.
Post-transcriptional regulation via small regulatory RNAs (sRNAs) has been implicated in diverse regulatory processes in bacteria, including virulence. One class of sRNAs, termed trans-acting sRNAs, can affect the stability and/or the translational efficiency of regulated transcripts. In this study, we utilized a collaborative approach that employed data from infection with the Borrelia burgdorferi Tn library, coupled with Tn-seq, together with borrelial sRNA and total RNA transcriptomes, to identify an intergenic trans-acting sRNA, which we designate here as ittA for infectivity-associated and tissue-tropic sRNA locus A. The genetic inactivation of ittA resulted in a significant attenuation in infectivity, with decreased spirochetal load in ear, heart, skin and joint tissues. In addition, the ittA mutant did not disseminate to peripheral skin sites or heart tissue, suggesting a role for ittA in regulating a tissue-tropic response. RNA-Seq analysis determined that 19 transcripts were differentially expressed in the ittA mutant relative to its genetic parent, including vraA, bba66, ospD and oms28 (bba74). Subsequent proteomic analyses also showed a significant decrease of OspD and Oms28 (BBA74) proteins. To our knowledge this is the first documented intergenic sRNA that alters the infectivity potential of B. burgdorferi.


Evidence-based Surgery of Aortic Regurgitation: Results of a Questionnaire in German-speaking Countries.
evidence-based medicine (EBM) approaches have reached broad acceptance, both in conservative and surgical disciplines. The aim of this study is to clarify the role of EBM in a rare condition of aortic regurgitation (AR) with surgical indication. A purpose-built Internet-based questionnaire was sent to 607 cardiovascular surgeons in Germany, Austria, and Switzerland. A virtual 64-year-old patient's medical history was presented, including two ultrasound images and one computed tomography scan, showing a 58-mm aortic root aneurysm and a severe trileaflet regurgitant aortic valve. Participants had to choose their preferred therapeutic strategy from a list. Additionally, demographics including nationality, the center size, and the frequency of similar types of patients referred to their departments were collected. Of 607 questionnaires, 100 were returned (16%). One participant was excluded due to conflicting answers. Most surgeons (n = 84; 84%) chose a valve-sparing root replacement (VSRR). A Bentall procedure was preferred by 13 surgeons (13%). Two surgeons voted for aortic valve replacement combined with partial root resection. The decision-making process was not significantly influenced by center size, nationality, or frequency of patients. Applying the current guidelines to our virtual study patient, 84% of participants acted accordingly choosing VSRR. Remarkably, 14% of these surgeons see less than 10 and 43% see not more than 20 comparable patients per year. Since the guidelines reserve VSRR for competent centers, those numbers as well as the guidelines themselves should be further discussed.


Healing and curing: issues in the social history and anthropology of medicine in Africa.
Metaphors of disease, illness and healing, though they operate in different ways in different cultures and historical periods, appear to have a remarkably common currency. This fact presents both problems and opportunities for the medical anthropologist and historian, and raises important issues of interpretation for both disciplines. The problem of defining the field of analysis in this wide-ranging world of health and sickness has led to a variety of solutions. Some have begun with a biological definition of illness; others have started with a cultural definition. No one definition will be appropriate for all purposes and a plurality of approaches is to be welcomed. However, there is a tendency evident in the literature on medicine and healing in Africa which may lead to the drawing of misleading comparisons between African healing practices and scientific medicine. Whilst the former are described in all their cultural complexity, the latter is often described by reference, not to practice, but to this system's theory of itself. Since elements of both the theory and the practices of scientific medicine now form part of many African healing practices, this tendency may obscure the dynamic reality of the world of healing and curing in contemporary Africa.


Fundamental study of a newly developed medium on detection of Lactobacillus.
To investigate the specificity of a newly developed Lactobacillus medium (LB medium) and its usefulness for the detection of Lactobacillus. Chlorophenol red was added to Rogosa SL Broth to make the LB medium whose pH was adjusted to 5.90. After incubation of Lactobacillus in LB medium for 24 hours, the correlation between the number of bacteria and the medium pH was examined. The change of pH was also examined when other microbes coexisted with Lactobacillus. Six species of Lactobacillus were tested. The medium pH decreased to 4 approximately 5 after incubation of any of these species for 24 hours. Though there were some differences in the acid-producing ability among species, a significant negative correlation (r = -0.93 approximately -0.99) was found between the initial number of bacteria and the medium pH with all species tested. The color of the medium did not change after incubation of other bacteria that might also be found in the normal vagina. The performance of the medium was not affected by the presence of large numbers of other microbes. In L. gasseri JCM 1131, the test microbe for color sample, the number of microbes whose color changed (red-->orange-->yellow) were approximately consistent with that of microbes reported in bacterial vaginosis (BV). This method can be easily applied to detect Lactobacillus species as the number of Lactobacillus can be estimated based on the change in color of the medium for less than 24 hours after incubation.


Families of adolescent clients and nonclients: their environments and help-seeking behaviors.
Family demographic characteristics, family structure, family environment, and help-seeking variables were explored through interviews with two groups of Afro-American adolescents, including 52 clients and 52 nonclients. One parent of each adolescent was also interviewed. The ratio of single-parent families in the two groups differed significantly. Using one-way analysis of variance, significant differences were found between the means of the groups on five of the ten Family Environment Scale (FES) subscales. The family groups differed significantly on only one help-seeking variable, use of formal helpers. Adolescent client families reported using formal helpers more than did adolescent nonclient families (F = 2.69; df 102; p less than 0.05).


Nasopharyngeal Carriage Rate of Streptococcus pneumoniae, Related Risk Factors, and Antibiotic Susceptibility Among Inmates in Hawassa Central Prison Institute: Hawassa, Sidama National Region, Ethiopia.
The bacterium Streptococcus pneumoniae commonly causes severe bacterial illnesses in both children and adults. S. pneumoniae is the most fatal bacterial pathogen, causing 50% of the deaths from lower respiratory infections in people of all ages. This study was aimed to determine a nasopharyngeal carriage rate of S. pneumoniae, related risk factors, and antibiotic susceptibility among prisoners in Hawassa Central Prison Institute Hawassa, Ethiopia. From July to August 2021, a cross-sectional investigation was carried out in Hawassa prison. All randomly chosen adult volunteers were a part of the study. In this study, about 330 different people were included. Within 3 h of collection, the swab specimen was inoculated onto 5% sheep blood agar; the inoculated medium was then incubated for 18-24 h at 35-37 °C in a CO2-enriched environment. Following incubation, the S. pneumoniae colonies were suspected, but the usual colony shape, alpha-hemolysis, Gram staining, optochin susceptibility, and bile solubility test allowed for confirmation. Antimicrobial susceptibility testing was carried out in accordance with the Clinical and Laboratory Standards Institute's guidelines. Overall carriage rate of S. pneumoniae among adult individuals were 41 (12.7%). The carriage rate of S. pneumoniae was affected by age classes that 39-48 years (OR = 4.82, 95%CI = 1.49-15.56, p = .009), 49-58 years (OR = 5.27, 95%CI = 1.27-21.89, p = .022), and greater than 58 years (OR = 4.36, 95%CI = 1.13-16.90, p = .033); cigarette smoking (OR = 3.41, 95%CI = 1.16-10.01, p = .026); and sharing beds (OR = 3.91, 95%CI = 1.27-12.07, p = .018). The majority of the isolates are susceptible for clindamycin (87.8%) and resistant for chloramphenicol (56%). Multidrug resistance was observed in 36.7%. The overall carriage rate of S. pneumoniae was 12.7%. Age, cigarette smoking, and sharing beds in the same prison room had a substantial impact on this nasopharyngeal carriage rate. Chloramphenicol (56%), erythromycin (41.5%), tetracycline (39%), and co-trimoxazole (34.1%) resistance were seen in the majority of S. pneumoniae isolates. Early detection, hygiene maintenance, and appropriate treatment are necessary.


Improved Solid Electrolyte Conductivity via Macromolecular Self-Assembly: From Linear to Star Comb-like P(S-co-BzMA)-b-POEGA Block Copolymers.
Star block copolymer electrolytes with a lithium-ion conducting phase are investigated in the present work to assess the influence of this complex architecture compared to that of the linear one, on both, bulk morphology and ionic conductivity. For that purpose, the controlled synthesis of a series of poly(styrene-co-benzyl methacrylate)-b-poly[oligo(ethylene glycol) methyl ether acrylate] [P(S-co-BzMA)-b-POEGA] block copolymers (BCPs) by reversible addition-fragmentation transfer polymerization was performed from either a monofunctional or a tetrafunctional chain transfer agent containing trithiocarbonate groups. We emphasized how a small amount of styrene (6 mol %) drastically improved the control of the RAFT polymerization of benzyl methacrylate mediated by the tetrafunctional chain transfer agent. Transmission electron microscopy and small-angle X-ray scattering demonstrated a clear segregation of the BCPs in the presence of lithium salt. Interestingly, the star BCPs gave rise to highly ordered lamellar structures as compared to that of the linear analogues. Consequently, the reduced lamellae tortuosity of self-assembled star BCPs improved the lithium conductivity by more than 8 times at 30 °C for ∼30 wt % of the POEGA conductive phase.


Endophenotypes in bipolar disorder.
The search for genes in bipolar disorder has provided numerous genetic loci that have been linked to susceptibility to developing the disorder. However, because of the genetic heterogeneity inherent in bipolar disorder, additional strategies may need to be employed to fully dissect the genetic underpinnings. One such strategy involves reducing complex behaviors into their component parts (endophenotypes). Abnormal neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, and neuropsychological findings are characteristics that often accompany psychiatric illness. It is possible that some of these may eventually be useful in subdefining complex genetic disorders, allowing for improvements in diagnostic assessment, genetic linkage studies, and development of animal models. Findings in patients with bipolar disorder that may eventually be useful as endophenotypes include abnormal regulation of circadian rhythms (the sleep/wake cycle, hormonal rhythms, etc.), response to sleep deprivation, P300 event-related potentials, behavioral responses to psychostimulants and other medications, response to cholinergics, increase in white matter hyperintensities (WHIs), and biochemical observations in peripheral mononuclear cells. Targeting circadian rhythm abnormalities may be a particularly useful strategy because circadian cycles appear to be an inherent evolutionarily conserved function in all organisms and have been implicated in the pathophysiology of bipolar disorder. Furthermore, lithium has been shown to regulate circadian cycles in diverse species, including humans, possibly through inhibition of glycogen synthase kinase 3-beta (GSK-3beta), a known target of lithium.


Evolutionary ecology of the marine Roseobacter clade.
Members of the Roseobacter clade are equipped with a tremendous diversity of metabolic capabilities, which in part explains their success in so many different marine habitats. Ideas on how this diversity evolved and is maintained are reviewed, focusing on recent evolutionary studies exploring the timing and mechanisms of Roseobacter ecological diversification.


Observation of posterior corneal vesicles with in vivo confocal microscopy and anterior segment OCT.
The histopathology of posterior corneal vesicles (PCV) has not yet been revealed. A 15-year-old girl, who was diagnosed by slit-lamp microscopy as PCV, was examined using specular microscopy, in vivo confocal microscopy, and anterior segment OCT (optical coherence tomography). Anterior segment OCT showed that the thickness of both corneas was within normal limits. At the same time, in vivo confocal microscopy revealed endothelial cells in the rounded dark areas, acellular hyporeflective layers on the Descemet's membrane, and hyperreflective linear lesions. These findings were not reported previously by slit-lamp and specular microscopy. The abnormal findings only existed at the Descemet's membrane and corneal endothelial layer. Previous reports dealing with posterior polymorphous dystrophy (PPMD) examined using in vivo confocal microscopy reported almost the same findings, suggesting that PCV and PPMD may be the same at the microstructural level.


A new elastic slot system and V-wire mechanics.
To biomechanically test a new elastic slot system and V-wire mechanics. Conventional twin and self-ligating brackets and the new elastodynamic bracket were biomechanically tested. The conventional brackets had a rectangular 0.022'' slot and the new elastodynamic bracket had a V-slot, a new slot geometry. Torque measurements were performed with 0.018'' × 0.025'' and 0.019'' × 0.025'' stainless steel (ss) archwires. A nickel-titanium V wire was used for the biomechanical measurements on the elastodynamic bracket. The measurements were done with the aid of a six-component measuring sensor. The results of the biomechanical testing revealed play in the brackets with rectangular slot geometry. The V slot in the elastodynamic bracket assured that the wire fit perfectly in the slot. Dynamic moments of 5 to 10 Nmm were transmitted without any play. No permanent deformation of the slot occurred in the new elastodynamic bracket because of the elastic slot. Control of torque for three-dimensional positioning of the teeth in the dental arch with rectangular slot geometry as used in straight-wire therapy is difficult. If torque is bent into the wire, because of the play there is a high risk that either too much, too little, or no moment is transmitted to the teeth. The V-slot archwire/bracket geometry in conjunction with nickel titanium composition has no play and allows a reduction of forces and moments with direct and continuous transmission of torque in the bracket. Because of the elasticity of the bracket, there is an upper limit to the moment possible.


N-3 (omega-3) Fatty acids in postpartum depression: implications for prevention and treatment.
A growing body of clinical and epidemiological evidence suggests that low dietary intake and/or tissue levels of n-3 (omega-3) polyunsaturated fatty acids (PUFAs) are associated with postpartum depression. Low tissue levels of n-3 PUFAs, particularly docosahexaenoic acid (DHA), are reported in patients with either postpartum or nonpuerperal depression. Moreover, the physiological demands of pregnancy and lactation put childbearing women at particular risk of experiencing a loss of DHA from tissues including the brain, especially in individuals with inadequate dietary n-3 PUFA intake or suboptimal metabolic capabilities. Animal studies indicate that decreased brain DHA in postpartum females leads to several depression-associated neurobiological changes including decreased hippocampal brain-derived neurotrophic factor and augmented hypothalamic-pituitary-adrenal responses to stress. Taken together, these findings support a role for decreased brain n-3 PUFAs in the multifactorial etiology of depression, particularly postpartum depression. These findings, and their implications for research and clinical practice, are discussed.


Factors Associated with Dental Fear and Anxiety in Children Aged 7 to 9 Years.
The aim was to investigate changes in dental fear and anxiety (DFA) and verify factors associated with DFA in children. A longitudinal cohort study that included 160 children aged 7 years was carried out. A questionnaire was completed by parents at two time points and evaluated the immigrant background, maternal education, whether the child had ever had toothache, and whether the parents had dental fear. The oral clinical examination evaluated decayed, extracted, and filled primary teeth (deft). The children's fear survey schedule dental subscale (CFSS-DS) was used to assess the dental fear of the children. Multilevel mixed-effects logistic regressions analyses were used. The CFSS-DS found that 7% of the children had dental fear at age 7 and mean CFSS-DS was 22.9. At 9 years of age, 8% reported dental fear and the mean increased to 25.4. Parental dental fear, experience of toothache, and report of painful dental treatment and caries development between 7 and 9 years of age were factors that were significantly related to development of DFA. There was a change in DFA between 7 and 9 years of age. Dental fear and anxiety is a dynamic process in growing individuals and is significantly related to painful symptoms and experiences of dental care as well as parental dental fear.


Public awareness, concerns, and priorities about anthropogenic impacts on marine environments.
Numerous international bodies have advocated the development of strategies to achieve the sustainability of marine environments. Typically, such strategies are based on information from expert groups about causes of degradation and policy options to address them, but these strategies rarely take into account assessed information about public awareness, concerns, and priorities. Here we report the results of a pan-European survey of public perceptions about marine environmental impacts as a way to inform the formation of science and policy priorities. On the basis of 10,106 responses to an online survey from people in 10 European nations, spanning a diversity of socioeconomic and geographical areas, we examine the public's informedness and concern regarding marine impacts, trust in different information sources, and priorities for policy and funding. Results show that the level of concern regarding marine impacts is closely associated with the level of informedness and that pollution and overfishing are two areas prioritized by the public for policy development. The level of trust varies greatly among different information sources and is highest for academics and scholarly publications but lower for government or industry scientists. Results suggest that the public perceives the immediacy of marine anthropogenic impacts and is highly concerned about ocean pollution, overfishing, and ocean acidification. Eliciting public awareness, concerns, and priorities can enable scientists and funders to understand how the public relates to marine environments, frame impacts, and align managerial and policy priorities with public demand.


An inexpensive method of negative pressure wound therapy for extremities.
Negative pressure wound therapy (NPWT) is an established method for the faster wound healing of chronic non-healing wounds. It is also used for laparostomy wounds and healing of split skin grafts. The commercially available machine and the consumables for NPWT are very expensive and economically not feasible in developing and underdeveloped countries. So, we devised a NPWT system for wounds of the extremity using inexpensive, readily available materials in any hospital. The materials used are sterile glove, autoclaved sponge, Foley catheter, and a wall suction unit. The sponge was placed over the wound, and a sterile glove was pulled over it. A Foley catheter was placed over the sponge and taken out through one of the fingers of the glove. Adhesive plaster was used to air-seal the glove. The Foley catheter was fixed with silk ties and connected to wall suction. Granulation and wound healing was faster in this system. This system was safe and inexpensive for the treatment of wounds of the extremity.


Adaptive Task-Space Cooperative Tracking Control of Networked Robotic Manipulators Without Task-Space Velocity Measurements.
In this paper, the task-space cooperative tracking control problem of networked robotic manipulators without task-space velocity measurements is addressed. To overcome the problem without task-space velocity measurements, a novel task-space position observer is designed to update the estimated task-space position and to simultaneously provide the estimated task-space velocity, based on which an adaptive cooperative tracking controller without task-space velocity measurements is presented by introducing new estimated task-space reference velocity and acceleration. Furthermore, adaptive laws are provided to cope with uncertain kinematics and dynamics and rigorous stability analysis is given to show asymptotical convergence of the task-space tracking and synchronization errors in the presence of communication delays under strongly connected directed graphs. Simulation results are given to demonstrate the performance of the proposed approach.


Antibacterial effect of water-soluble chitosan on representative dental pathogens Streptococcus mutans and Lactobacilli brevis.
Dental caries is still a major oral health problem in most industrialized countries. The development of dental caries primarily involves Lactobacilli spp. and Streptococcus mutans. Although antibacterial ingredients are used against oral bacteria to reduce dental caries, some reports that show partial antibacterial ingredients could result in side effects. The main objective is to test the antibacterial effect of water-soluble chitosan while the evaluation of the mouthwash appears as a secondary aim. The chitosan was obtained from the Application Chemistry Company (Taiwan). The authors investigated the antibacterial effects of water-soluble chitosan against oral bacteria at different temperatures (25-37 ºC) and pH values (pH 5-8), and evaluated the antibacterial activities of a self-made water-soluble chitosan-containing mouthwash by in vitro and in vivo experiments, and analyzed the acute toxicity of the mouthwashes. The acute toxicity was analyzed with the pollen tube growth (PTG) test. The growth inhibition values against the logarithmic scale of the test concentrations produced a concentration-response curve. The IC50 value was calculated by interpolation from the data. The effect of the pH variation (5-8) on the antibacterial activity of water-soluble chitosan against tested oral bacteria was not significant. The maximal antibacterial activity of water-soluble chitosan occurred at 37 ºC. The minimum bactericidal concentration (MBC) of water-soluble chitosan on Streptococcus mutans and Lactobacilli brevis were 400 µg/mL and 500 µg/mL, respectively. Only 5 s of contact between water-soluble chitosan and oral bacteria attained at least 99.60% antibacterial activity at a concentration of 500 µg/mL. The water-soluble chitosan-containing mouthwash significantly demonstrated antibacterial activity that was similar to that of commercial mouthwashes (>99.91%) in both in vitro and in vivo experiments. In addition, the alcohol-free mouthwash exhibited no cytotoxicity and no oral stinging. To the best of our knowledge, this was the first study to combine in vitro and in vivo investigations to analyze the antibacterial properties of water-soluble chitosan-containing mouthwash. This study illustrated that water-soluble chitosan may be a viable alternative to commercial mouthwashes in the future.


Standardized evaluation of simultaneous integrated boost plans on volumetric modulated arc therapy.
The purpose of this paper is to quantify the capability of the RapidArc (RA) planning system to deliver highly heterogeneous doses for simultaneous integrated boost (SIB) in both a phantom and patients. A cylindrical planning target volume (PTV) with a diameter of 6 cm was created in a cylindrical phantom. A smaller boost tumor volume (BTV) in the PTV with varying diameters (0.625-2.5 cm), positions and shapes was also created. Five previously treated patients with brain tumors were included in the study. Original gross tumor volumes (average 41.8 cm(3)) and PTVs (average 316 cm(3)) were adopted as the BTV and the PTV in the new plans. 30 Gy was prescribed to the PTV. Doses varying from 35 to 90 Gy were prescribed to the BTV. Both SIB and sequential boost (SEQ) plans were created on RA to meet the prescription. A set of reference plans was also created on the helical tomotherapy (HT) platform. Normalized dose contrast (NDC) and the integral dose were used to evaluate the quality of plans. NDC was defined as the dose contrast between BTV and PTV-BTV, normalizing to the ideal scenario where the contrast is the ratio between prescribed doses to the BTV and PTV. NDC above 90% was observed with BTV dose less than 60 Gy. NDC was minimally affected by the size of BTV but adversely affected by the complexity of the shape of the BTV. In the phantom plans, a peak of NDC was observed with 45 Gy (150% of PTV dose) to the BTV; for BTVs at the center of the PTV, the increase in the integral dose was less than 2% and remained constant for all dose levels in the phantom plans but a linear increase in the integral dose was observed with the HT plans. In the patient plans, an 11% average increase in the integral dose was observed with SIB plans and 60 Gy to the BTV, lower than the 30% average increase in the SEQ plans by RA and 25% by HT. The study showed not only that SIB by RA can achieve superior plans compared with SEQ plans on the same platform and SIB plans on HT, but also the feasibility to optimize prescription dose in a SIB plan. A maximal therapeutic ratio can be achieved with BTV dose 50-100% higher than the PTV dose, depending on the shape and position of the tumor.


Spectrophotometric determination of iodine species in table salt and pharmaceutical preparations.
A sensitive spectrophotometric method for the determination of iodine species like iodide, iodine, iodate and periodate is described. The method involves the oxidation of iodide to ICl(2)(-) in the presence of iodate and chloride in acidic medium. The formed ICl(2)(-) bleaches the dye methyl red. The decrease in the intensity of the colour of the dye is measured at 520 nm. Beer's law is obeyed in the concentration range 0-3.5 microg of iodide in an overall volume of 10 ml. The molar absorptivity of the colour system is 1.73 x 10(5) l mol(-1) cm(-1) with a correlation coefficient of -0.9997. The relative standard deviation is 3.6% (n=10) at 2 microg of iodide. The developed method can be applied to samples containing iodine, iodate and periodate by prereduction to iodide using Zn/H(+) or NH(2)NH(2)/H(+). The effect of interfering ions on the determination is described. The proposed method has been successfully applied for the determination of iodide and iodate in salt samples and iodine in pharmaceutical preparations.


Strengthening public health surveillance and response using the health systems strengthening agenda in developing countries.
There is increased interest in strengthening health systems for developing countries. However, at present, there is common uncertainty about how to accomplish this task. Specifically, several nations are faced with an immense challenge of revamping an entire system. To accomplish this, it is essential to first identify the components of the system that require modification. The World Health Organization (WHO) has proposed health system building blocks, which are now widely recognized as essential components of health systems strengthening.With increased travel and urbanization, the threat of emerging diseases of pandemic potential is increasing alongside endemic diseases such as human immunodeficiency virus (HIV), tuberculosis (TB), malaria, and hepatitis virus infections. At the same time, the epidemiologic patterns are shifting, giving rise to a concurrent increase in disease burden due to non-communicable diseases. These diseases can be addressed by public health surveillance and response systems that are operated by competent public health workers in core public health positions at national and sub-national levels with a focus on disease prevention.We describe two ways that health ministries in developing countries could leverage President Obama's Global Health Initiative (GHI) to build public health surveillance and response systems using proven models for public health systems strengthening and to create the public health workforce to operate those systems. We also offer suggestions for how health ministries could strengthen public health systems within the broad health systems strengthening agenda. Existing programs (e.g., the Global Vaccine Alliance [GAVI] and the Global Fund Against Tuberculosis, AIDS, and Malaria [GFTAM]) can also adapt their current health systems strengthening programs to build sustainable public health systems.


Postgrowth Substitutional Tin Doping of 2D WS2 Crystals Using Chemical Vapor Deposition.
Doping of two-dimensional materials provides them tunable physical properties and widens their applications. Here, we demonstrate the postgrowth doping strategy in monolayer and bilayer tungsten disulfide (WS2) crystals, which utilizes a metal exchange mechanism, whereby Sn atoms become substitutional dopants in the W sites by energetically favorable replacement. We achieve this using chemical vapor deposition techniques, where high-quality grown WS2 single crystals are first grown and then subsequently reacted with a SnS precursor. Thermal control of the exchange doping mechanism is revealed, indicating that a sufficiently high enough temperature is required to create the S vacancies that are the initial binding sites for the SnS precursor and metal exchange occurrence. This results in a better control of dopant distribution compared to the tradition all-in-one approach, where dopants are added during the growth phase. The Sn dopants exhibit an n-type doping behavior in the WS2 layers based on the decreased threshold voltage obtained from transistor device measurements. Annular dark-field scanning transmission electron microscopy shows that in bilayer WS2 the Sn doping occurs only in the top layer, creating vertical heterostructures with atomic layer doping precision. This postgrowth modification opens up ways to selectively dope one layer at a time and construct mixed stoichiometry vertical heterojunctions in bilayer crystals.


Vapor phase processing: a novel approach for fabricating functional hybrid materials.
Materials science is nowadays facing challenges in optimizing properties of materials which are needed for numerous technological applications and include, but are not limited to, mechanics, electronics, optics, etc. The key issue is that for emerging applications materials are needed which incorporate certain properties from polymers or biopolymers and metals or ceramics at the same time, thus fabrication of functional hybrid materials becomes inevitable. Routes for the synthesis of functional hybrid materials can be manifold. Among the explored routes vapor phase processing is a rather novel approach which opts for compatibility with many existing industrial processes. This topical review summarizes the most important approaches and achievements in the synthesis of functional hybrid materials through vapor phase routes with the goal to fabricate suitable hybrid materials for future mechanical, electronic, optical or biomedical applications. Most of the approaches rely on atomic layer deposition (ALD) and techniques related to this process, including molecular layer deposition (MLD) and vapor phase infiltration (VPI), or variations of chemical vapor deposition (CVD). The thus fabricated hybrid materials or nanocomposites often show exceptional physical or chemical properties, which result from synergies of the hybridized materials families. Even though the research in this field is still in its infancy, the initial results encourage further development and promise great application potential in a large variety of applications fields such as flexible electronics, energy conversion or storage, functional textile, and many more.


Entamoeba dispar: cultivation with sterilized Crithidia fasciculata.
Four isolates of Entamoeba dispar identified by their hexokinase and phosphoglucomutase isoenzyme profile and by their failure to react with Entamoeba histolytica-specific monoclonal antibody (4G6) could be grown in either Diamond's BI-S-33 medium, newly developed BCSI-S (Biosate cysteine starch iron-serum) medium, or casein-free YI-S medium in the presence of Crithidia fasciculata (ReF-1:PRR) sterilized by heating 56 degrees C for 30 min and subsequent incubation with 1% hydrogen peroxide for 24 hours at 4 degrees C. After the cultures were maintained for over 50 passages, the amebae were identified as E. dispar by isoenzyme analysis, polymerase chain reaction with E. histolytica- and E. dispar-specific primers, i.e. p11 plus p12 and p13 plus p14, respectively, and by negative reactivity with monoclonal antibody 4G6. The flagellates added to the culture were judged to be metabolically inactive based on the results of nuclear magnetic resonance spectroscopy, electron microscopy, and polarographic analysis. All of these findings suggest that E. dispar can grow in vitro with metabolically inactive C. fasciculata as a culture associate.


Comparison of use by enrolled and recently disenrolled populations in a health maintenance organization.
The demographic characteristics and ambulatory use of health maintenance organization (HMO) members who voluntarily disenrolled from an HMO--those who returned to the alternative health insurance plan--or who involuntarily disenrolled due to job loss or change--were compared with those of persons still enrolled. The database for all three samples was comprised of ambulatory use data for 6 months (July 1979-December 1979). The HMO-enrolled sample made significantly more visits for health services, on the average, than either of the disenrolled samples. Upon controlling for demographic variables (age, sex, family size, and years enrolled), it was ascertained that young to middle-aged women from families of three or more, making visits for chronic problems, made the greater use among the enrolled sample. The relationship of these findings to the risk vulnerability theory of HMO enrollment choice is discussed, and long-term implications for HMOs are presented.


The binding of ascorbate to bovine serum albumin.
Ultrafiltration has been used to investigate the interaction of ascorbate with bovine serum albumin in 0.1 M sodium phosphate buffer, pH 6.5. The results are interpreted in terms of the binding of ascorbate to four equivalent and independent protein sites, governed by an intrinsic association constant of 2 600 +/- 700 M-1 at 20 degrees C, thereby providing evidence for specificity of the interaction over a range of vitamin concentration (0.08-1.5 mM) pertinent to the physiological situation.


Vegetation structure and photosynthesis respond rapidly to restoration in young coastal fens.
Young coastal fens are rare ecosystems in the first stages of peatland succession. Their drainage compromises their successional development toward future carbon (C) reservoirs. We present the first study on the success of hydrological restoration of young fens. We carried out vegetation surveys at six young fens that represent undrained, drained, and restored management categories in the Finnish land uplift coast before and after restoration. We measured plant level carbon dioxide (CO2) assimilation and chlorophyll fluorescence (Fv/Fm) from 17 most common plant species present at the sites. Within 5 years of restoration, the vegetation composition of restored sites had started to move toward the undrained baseline. The cover of sedges increased the most in response to restoration, while the cover of deciduous shrubs decreased the most. The rapid response indicates high resilience and low resistance of young fen ecosystems toward changes in hydrology. Forbs had higher photosynthetic and respiration rates than sedges, deciduous shrubs, and grasses, whereas rates were lowest for evergreen shrubs and mosses. The impact of management category on CO2 assimilation was an indirect consequence that occurred through changes in plant species composition: Increase in sedge cover following restoration also increased the potential photosynthetic capacity of the ecosystem. Synthesis and applications. Restoration of forestry drained young fens is a promising method for safeguarding them and bringing back their function as C reservoirs. However, their low resistance to water table draw down introduces a risk that regeneration may be partially hindered by the heavy drainage in the surrounding landscape. Therefore, restoration success is best safeguarded by managing the whole catchments instead of carrying out small-scale projects.


Characterization of aziridinylbenzoquinone DNA cross-links by liquid chromatography-infrared multiphoton dissociation-mass spectrometry.
DNA cross-linking was evaluated by liquid chromatography-tandem mass spectrometry to determine the relative cross-linking abilities of two aziridinylbenzoquinones. Reactivities of RH1 (2,5-diaziridinyl-3-[hydroxymethyl]-6-methyl-1,4-benzoquinone), a clinically studied antitumor cross-linking agent, and an analogue containing a phenyl group (2,5-diaziridinyl-3-[hydroxymethyl]-6-phenyl-1,4-benzoquinone, PhRH1) rather than a methyl group were compared. The bulky phenyl substituent was added to determine the impact of steric hindrance on the formation of cross-links within a double helical structure. Cross-links formed by RH1 and PhRH1 were observed at 5'-dGNC sites as well as 5'-dGAAC/dGTTC sites. RH1 was more effective at forming cross-links than PhRH1 for a variety of duplexes. Infrared multiphoton dissociation (IRMPD) and collision-induced dissociation results confirmed the presence and the location of the cross-links within the duplexes, and IRMPD was used to identify the dissociation pathways of the cross-linked duplexes.


Antifungal Secondary Metabolites Produced by the Fungal Endophytes: Chemical Diversity and Potential Use in the Development of Biopesticides.
Plant diseases caused by phytopathogenic fungi can lead to huge losses in the agricultural fields and therefore remain a continuous threat to the global food security. Chemical-based fungicides contributed significantly in securing crop production. However, indiscriminate application of fungicides has led to increased chemical resistance and potential risks to human health and environment. Thus, there is an urgent need for searching for new bioactive natural products and developing them into new biopesticides. Fungal endophytes, microorganisms that reside in the fresh tissues of living plants, are regarded as untapped sources of novel natural products for exploitation in agriculture and/or medicine. Chemical examination of endophytic fungi has yielded enormous antifungal natural products with potential use in the development of biopesticides. This review summarizes a total of 132 antifungal metabolites isolated from fungal endophytes in the past two decades. The emphasis is on the unique chemical diversity of these metabolic products, together with their relevant antifungal properties. Moreover, some "star molecules," such as griseofulvin and trichothecene, as well as their synthetic derivatives that possess high potential as candidates of new natural fungicides, are also presented herein.


[Jan Ewangelista Purkynie, and the Annals of the the Medical Faculty].
Jan Ewangelista Purkynĕ, the founder of the modern physiology and histology, professor of the University in Wrocław (1823-1850), deserve a reward not only to the Czech national culture, but also made much to approach our countries. But what is less known is the fact concerning his cooperation with Annals of the Medical Faculty in Jagiellonian University and his additional office professors Józef Majer and Franciszek Skobel. This first publication on the subject of cardiacl conductional fibres, later caller Purkynĕ's fibres reveals in the second volume of Annals of Medical Faculty in Jagiellonian University AD 1839, six years before the publication in German. Bogusław Palicki was one of the fourteen doctoral students Wrocław Physiological School J.E. Purkynĕ. It is necessary to underline not only Purkynĕ vivid connection with eminent personage in those days of European science-with Cracow colleagues and his research organ-but also a high scientific and additional standard of Annals, which ended their life with the fall of the Cracow Republic AD 1846. Purkynĕ's studies and discoveries also in the present time are of lasting scientific as well as medico-historical values.


Antihyperglycemic, antistress and nootropic activity of roots of Rubia cordifolia Linn.
Effect of alcoholic extract of roots of Rubia cordifolia was studied on elevated blood glucose level in alloxan treated animals. The extract reduced the blood sugar level raised by alloxan. Effect of alcoholic extract was also investigated on cold restraint induced stress and on scopolamine-induced memory impairment. Alcoholic extract enhanced brain gamma-amino-n-butyric acid (GABA) levels and decreased brain dopamine and plasma corticosterone levels. Acidity and ulcers caused due to cold restraint stress were inhibited by alcoholic extract. Animals treated with alcoholic extract spent more time in open arm in elevated plus maze model. It also antagonized scopolamine induced learning and memory impairment. Baclofen induced catatonia was potentiated by alcoholic extract.


A Submicron-Scale Plugging Agent for Oil-Based Drilling Fluid Synthesized Using the Inverse Emulsion Polymerization Method.
Due to the increasing difficulty of drilling in the later stages of oil and gas field development, the development of micro-pores and micro-fractures is becoming common. Conventional plugging agents have relatively large particle sizes. So, choosing the appropriate plugging agent can prevent leakages. Using the inverse emulsion polymerization method, acrylamide, 2-acrylamide-2-methylpropane sulfonic acid and acrylic acid were selected to be the main reaction monomers, N,N'-methylenebisacrylamide was used as a crosslinking agent, sorbitan monostearate and polyoxyethylene sorbitan anhydride monostearate were used as emulsifiers, and 2,2'-azobis(2-methylpropionamidine) dihydrochloride was used as the initiator to synthesize a nano-scale plugging agent for oil-based drilling fluid. The plugging agent was characterized using infrared spectroscopy, scanning electron microscopy, and thermogravimetry analysis. The results showed that the plugging agent is spherical and uniform in size, with particles being in the submicron range. Additionally, it exhibited strong temperature resistance. Finally, the performance of the plugging agent was evaluated via experiments conducted under normal temperature and pressure, high-temperature and high-pressure, and core-plugging conditions. After adding the plugging agent to the oil-based drilling fluid, the basic rheological properties of the oil-based drilling fluid were not significantly affected. Furthermore, the filtration loss was significantly reduced under normal temperature and pressure, as well as under high-temperature and high-pressure conditions, after aging. When the plugging agent with 3% concentration was added, the reduction rate of pore core permeability reached 96.04%. Therefore, the plugging agent for the oil-based drilling fluid can effectively improve the wellbore stability and has a promising potential for field applications.