Atomic-resolution chemical mapping of ordered precipitates in Al alloys using energy-dispersive X-ray spectroscopy.
Scanning transmission electron microscopy (STEM) coupled with energy-dispersive X-ray spectroscopy (EDS) is a common technique for chemical mapping in thin samples. Obtaining high-resolution elemental maps in the STEM is jointly dependent on stepping the sharply focused electron probe in a precise raster, on collecting a significant number of characteristic X-rays over time, and on avoiding damage to the sample. In this work, 80kV aberration-corrected STEM-EDS mapping was performed on ordered precipitates in aluminium alloys. Probe and sample instability problems are handled by acquiring series of annular dark-field (ADF) images and simultaneous EDS volumes, which are aligned and non-rigidly registered after acquisition. The summed EDS volumes yield elemental maps of Al, Mg, Si, and Cu, with sufficient resolution and signal-to-noise ratio to determine the elemental species of each atomic column in a periodic structure, and in some cases the species of single atomic columns. Within the uncertainty of the technique, S and β" phases were found to have pure elemental atomic columns with compositions Al2CuMg and Al2Mg5Si4, respectively. The Q' phase showed some variation in chemistry across a single precipitate, although the majority of unit cells had a composition Al6Mg6Si7.2Cu2.


A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas.
Epidemiologic and preclinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia. To further study the chemopreventive potential of these nutrients, we conducted a randomized, double-blind, placebo-controlled trial of supplementation with vitamin D, calcium, or both for the prevention of colorectal adenomas. We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy. We randomly assigned 2259 participants to receive daily vitamin D3 (1000 IU), calcium as carbonate (1200 mg), both, or neither in a partial 2×2 factorial design. Women could elect to receive calcium plus random assignment to vitamin D or placebo. Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations, according to the endoscopist's recommendation. The primary end point was adenomas diagnosed in the interval from randomization through the anticipated surveillance colonoscopy. Participants who were randomly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter, relative to participants given placebo. Overall, 43% of participants had one or more adenomas diagnosed during follow-up. The adjusted risk ratios for recurrent adenomas were 0.99 (95% confidence interval [CI], 0.89 to 1.09) with vitamin D versus no vitamin D, 0.95 (95% CI, 0.85 to 1.06) with calcium versus no calcium, and 0.93 (95% CI, 0.80 to 1.08) with both agents versus neither agent. The findings for advanced adenomas were similar. There were few serious adverse events. Daily supplementation with vitamin D3 (1000 IU), calcium (1200 mg), or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00153816.).


Characterisation of an antibody coated microcantilever as a potential immuno-based biosensor.
In this study, we investigated the activity, stability, lifetime and re-usability of monoclonal antibodies to myoglobin covalently immobilised onto microfabricated cantilever surfaces. These sensing surfaces are of interest to us in the development of novel cantilever-based immunosensors. For such sensors the antibody layer represents the sensing element while the microcantilever acts as a mechanical transducer. A procedure for producing re-usable biological coatings has been tested with different independent techniques. An Enzyme Linked Immunosorbent Assay (ELISA) was used to determine the presence of an active antibody coating, and to monitor the lifetime and stability of the immobilised antibody. Through this analysis, the activity of the immobilised antibody layer was found to be more stable with the introduction of sucrose, as a stabilising agent. Sucrose was applied to the immobilised antibody layer after each regeneration step. The immobilised antibody was found to have a stable active lifetime for up to 7 weeks. Fluorescence microscopy was used to give information on the distribution of the coating on the gold and silicon nitride sides of the cantilever. Atomic Force Microscopy was used to determine the presence of the biological coating on the cantilever and to obtain information on the surface morphology of the biological element of the sensor. The combined results provide valuable information on the development of an optimised sensing element and demonstrate a set of methods to use for future sensor-to-sensor characterisation. Preliminary experimental results showing the antibody activity against myoglobin, detected with a microcantilever based sensor prototype confirmed the motivations and potentialities of the proposed immunosensing technique.


Self-written waveguide in methylene blue sensitized poly(vinyl alcohol)/acrylamide photopolymer material.
We report the observation of a self-written waveguide inside a bulk methylene blue sensitized poly/vinyl alcohol)/acrylamide photopolymer material. Light from a low power He-Ne laser is focused into the material, and the evolution of the beam is monitored. The refractive index of the material is modulated in the region of high intensity due to photobleaching and photopolymerization effects occurring in the material. As a result, the beam propagates through the medium without any diffraction effects.


Global gene expression profiling of the polyamine system in suicide completers.
In recent years, gene expression, genetic association, and metabolic studies have implicated the polyamine system in psychiatric conditions, including suicide. Given the extensive regulation of genes involved in polyamine metabolism, as well as their interconnections with the metabolism of other amino acids, we were interested in further investigating the expression of polyamine-related genes across the brain in order to obtain a more comprehensive view of the dysregulation of this system in suicide. To this end, we examined the expression of genes related to polyamine metabolism across 22 brain regions in a sample of 29 mood-disordered suicide completers and 16 controls, and identified 14 genes displaying differential expression. Among these, altered expression of spermidine/spermine N1-acetyltransferase, spermine oxidase, and spermine synthase, has previously been observed in brains of suicide completers, while the remainder of the genes represent novel findings. In addition to genes with direct involvement in polyamine metabolism, including S-adenosylmethionine decarboxylase, ornithine decarboxylase antizymes 1 and 2, and arginase II, we identified altered expression of several more distally related genes, including aldehyde dehydrogenase 3 family, member A2, brain creatine kinase, mitochondrial creatine kinase 1, glycine amidinotransferase, glutamic-oxaloacetic transaminase 1, and arginyl-tRNA synthetase-like. Many of these genes displayed altered expression across several brain regions, strongly implying that dysregulated polyamine metabolism is a widespread phenomenon in the brains of suicide completers. This study provides a broader view of the nature and extent of the dysregulation of the polyamine system in suicide, and highlights the importance of this system in the neurobiology of suicide.


Elementary-field expansions of genuine cross-spectral density matrices.
A necessary and sufficient nonnegative definiteness condition for the cross-spectral density matrix (CDM) is derived. It is also shown that this realizability condition allows the expansion of genuine CDMs in terms of recently introduced elementary fields, namely, mean-square coherent beams, and fields with position-independent stochastic behavior. The special case of uniformly polarized electromagnetic Schell-model sources is also analyzed.


Learning experiences of medical and pharmacy students at a student-run clinic in south africa and the development of a framework for learning.
Trinity Health Services (THS) is a free clinic that serves the homeless community of Braamfontein. The clinic is run by pharmacy and medical students registered in the Faculty of Health Sciences at the University of the Witwatersrand, assisted by academic staff. This setting provided an ideal space to document the interprofessional experiences between these two groups of students outside of formal lectures or clinical exposures. Therefore, the research question for this study was: What are the learning experiences of medical and pharmacy students working at an inner-city student-driven clinic? A convenience sampling method was employed. All students, who volunteered at the clinic on one or more occasion, were invited to participate in a discipline-specific focus group discussion (FGD). Four FGDs were held with between six and eight participants in each. The FGDs were facilitated by a faculty member not involved with the clinic. The recordings were transcribed verbatim and analyzed thematically, using Tesch's eight steps. The following three themes emerged relating to learning experiences: "add more tools to your toolbox;" learning from supervisors and peers, and "we can really make a difference." These themes formed the framework for learning at THS. Patient care is placed at the core of the framework, and recognizing that learning occurs through serving, three learning outcomes were identified, namely health and homelessness; communication; clinical and communication skills as well as primary health care. Learning was facilitated through interactions with peers, supervisors, and interprofessional relationships. The authentic learning experience led to development of accountability, communication, and responsibility. A framework emerged for learning from opportunities central to patient care.


A Cross-Sectional Comparison of the Prevalence of Obstructive Sleep Apnea Symptoms in Adults With Down Syndrome in Scotland and Japan.
Small studies in Western populations report a high prevalence of obstructive sleep apnea (OSA) in adults with Down syndrome. To date, ethnic differences have not been explored. A questionnaire sent to 2,752 adults with Down syndrome aged ≥16 years in Scotland and Japan (789 valid responses) estimated OSA prevalence based on reported symptoms. Symptoms were common in both countries, with snoring (p = 0.001) and arousals (p = 0.04) more prevalent in Japan. Estimated OSA prevalence in adults with Down syndrome was similar in the two countries, and raised in comparison with the general adult population (19.6% in Scotland and 14.3% in Japan; p = 0.08), though BMI was a confounder. Identification and treatment of OSA is recommended in adults with Down syndrome, regardless of ethnicity.


Deletions at the C-terminus of interferon gamma reduce RNA binding and activation of double-stranded-RNA cleavage by bovine seminal ribonuclease.
Recombinant interferon gamma (IFN-gamma) from three species activates the cleavage of double stranded (ds-) RNA by the dimeric RNAase isolated from bovine semen (BS-RNAase). Human and bovine IFN-gamma bind RNA tightly enough to inhibit cleavage by RNAase A [Schein, Haugg and Benner (1990) FEBS Lett. 270, 229-232]. Murine IFN-gamma and a proteolytic fragment of human IFN-gamma, both of which lack part of the positively charged C-terminus, bind RNA weakly and do not inhibit RNAase A. Their ability to activate BS-RNAase is proportional to their activity in the anti-viral assay. Two monoclonal antibodies that neutralize the anti-viral activity of human IFN-gamma inhibit the activation of BS-RNAase by both full-length and proteolysed human IFN-gamma. Our results demonstrate that the C-terminus of IFN-gamma contributes to RNA binding and activation of BS-RNAase, as well as to anti-viral activity.


SLCO1B1 genetic variation and hormone therapy in menopausal women.
Response to menopausal hormone therapy (MHT) shows individual variation. SLCO1B1 encodes the OATP1B1 transporter expressed in the liver that transports many endogenous substances, including estrone sulfate, from the blood into hepatocytes. This study evaluated the relationship between genetic variation in SLCO1B1 and response to MHT in women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS) at Mayo Clinic, Rochester, MN. KEEPS participants were randomized to oral conjugated equine estrogen (n = 33, oCEE), transdermal 17β-estradiol (n = 33, tE2), or placebo (n = 34) for 48 months. Menopausal symptoms (hot flashes, night sweats, insomnia, palpitations) were self-reported before treatment and at 48 months. Estrone (E1), E2, and sulfated conjugates (E1S, E2S) were measured using high-performance liquid chromatography-tandem mass spectrometry. SLCO1B1 rs4149056 (c.521T>C, p.Val174Ala) was genotyped using a TaqMan assay. After adjusting for treatment, there was a significant association between the SLCO1B1 rs4149056 TT genotype (encoding normal function transporter) and lower E1S, E1S/E1, and E2S (P = 0.032, 0.010, and 0.008, respectively) compared with women who were heterozygous (TC) or homozygous (CC) for the reduced function allele. The interactions between genotype, treatment, and E2S concentration were stronger in women assigned to tE2 (P = 0.013) than the women taking oCEE (P = 0.056). Among women assigned to active treatment, women with the CT genotype showed a significantly greater decrease in night sweats (P = 0.041) than those with the TT genotype. Individual variation in sulfated estrogens is explained, in part, by genetic variation in SLCO1B1. Bioavailability of sulfated estrogens may contribute to relief of night sweats.


Neural processing of emotions in traumatized children treated with Eye Movement Desensitization and Reprocessing therapy: a hdEEG study.
Eye Movement Desensitization and Reprocessing (EMDR) therapy has been proven efficacious in restoring affective regulation in post-traumatic stress disorder (PTSD) patients. However, its effectiveness on emotion processing in children with complex trauma has yet to be explored. High density electroencephalography (hdEEG) was used to investigate the effects of EMDR on brain responses to adults' emotions on children with histories of early maltreatment. Ten school-aged children were examined before (T0) and within one month after the conclusion of EMDR (T1). hdEEGs were recorded while children passively viewed angry, afraid, happy, and neutral faces. Clinical scales were administered at the same time. Correlation analyses were performed to detect brain regions whose activity was linked to children's traumatic symptom-related and emotional-adaptive problem scores. In all four conditions, hdEEG showed similar significantly higher activity on the right medial prefrontal and fronto-temporal limbic regions at T0, shifting toward the left medial and superior temporal regions at T1. Moreover, significant correlations were found between clinical scales and the same regions whose activity significantly differed between pre- and post-treatment. These preliminary results demonstrate that, after EMDR, children suffering from complex trauma show increased activity in areas implicated in high-order cognitive processing when passively viewing pictures of emotional expressions. These changes are associated with the decrease of depressive and traumatic symptoms, and with the improvement of emotional-adaptive functioning over time.


Hypoglycemia after pancreas transplantation.
Hypoglycemia is a serious complication of therapy for diabetes. Chronic hypoglycemia and the attendant decrease in quality of life have been rationales for advocating pancreas transplantation as an alternative treatment. However, reports have appeared that suggest that as high as 30-50% of pancreas transplant recipients have occasional symptoms of mild hypoglycemia. Therefore, we studied glucose and hormone levels in transplant recipients and healthy control subjects. We studied glucose and hormone levels in transplant recipients reporting frequent symptoms of hypoglycemia (n = 10), transplant recipients without symptoms of hypoglycemia (n = 9), and healthy control subjects (n = 8) after a mixed meal and during a subsequent 24-h modified fast. All transplant recipients were insulin-independent; were receiving prednisone, cyclosporine, and azothioprine; and had functioning grafts with systemic venous drainage. No significant differences were observed in the fasting glucose, insulin, C-peptide, or glucagon levels when comparing the symptomatic with the asymptomatic groups of patients who had undergone successful pancreas transplantation. Similarly, no significant differences were found in the immediate postprandial period after a mixed meal. However, during the subsequent 24-h fast, glucose levels fell lower in the symptomatic than in the asymptomatic group of patients receiving a transplanted pancreas (71+/-2 vs. 81+/-2 mg/dl, P < 0.002). During the fast, no significant differences were found in insulin, C-peptide, or glucagon levels when comparing asymptomatic to symptomatic groups. Of 10 symptomatic recipients of pancreas transplantation, 5 reported symptoms of hypoglycemia during the study. In four of these five subjects, the onset of symptoms corresponded to nadirs in serum glucose, which occurred at values 2 SD or more below the mean glucose observed for the control and the asymptomatic pancreas recipient groups. The serum glucose levels at the time of symptoms in these four subjects were 55, 66, 51, and 57 mg/dl. In each of these four subjects, symptoms abated and the glucose levels rose spontaneously without intervention. One of these four subjects had elevated insulin binding activity in his serum consistent with endogenous insulin antibodies. This individual had a serum glucose value of 55 mg/dl at the conclusion of the 24-h fast without symptoms. Among a group of pancreas transplant recipients reporting frequent symptoms of hypoglycemia, some individuals demonstrated transient, symptomatic postprandial hypoglycernia. With the exception of one recipient with insulin antibodies, no evidence was found for hypoglycemia during fasting. Although postprandial hypoglycemia may occur in some pancreas transplant recipients, it does not appear to be a highly significant clinical problem.


Herpes-like virus infection causing mortality of cultured abalone Haliotis diversicolor supertexta in Taiwan.
A herpes-like virus is demonstrated for the first time to be associated with high mortality rates in maricultured abalone Haliotis diversicolor supertexta in Taiwan. Histopathology of moribund abalone indicated that the nerve system was the primary target tissue. The lesions were characterised by tissue necrosis accompanied with infiltration of haemocytes. Electron microscopic examination demonstrated viral particles within the degenerated cerebral ganglion cells. The viruses were hexagonal, approximately 100 nm in diameter and had a single coat. Some viral particles contained a dense nucleoid, while others were empty. The ultrastructure and morphogenesis of the virus particles were consistent with those of the herpesvirus described from the oyster Crassostrea virginica. Experimental infection using supernatant collected from minced visceral organs and muscle of moribund abalone induced 100 % mortality through both intramuscular injection and bath treatments.


Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in hypertension and their relationship to cardiovascular risk and treatment: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).
Hypertension results in structural changes to the cardiac and vascular extracellular matrix (ECM). Matrix metalloproteinases (MMP) and their inhibitors (TIMP) may play a central role in the modulation of this matrix. We hypothesized that both MMP-9 and TIMP-1 would be abnormal in hypertension, reflecting alterations in ECM turnover, and that their circulating levels should be linked to cardiovascular (CHD) and stroke (CVA) risk scores using the Framingham equation. Second, we hypothesized that treatment would result in changes in ECM indices. Plasma MMP-9 and TIMP-1 were measured before and after treatment (median 3 years) from 96 patients with uncontrolled hypertension participating in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Pretreatment values were compared to circulating MMP-9 and TIMP-1 levels in 45 age- and sex-matched healthy controls. Circulating pretreatment MMP-9 and TIMP-1 levels were significantly higher in patients with hypertension than in the normotensive controls (P =.0041 and P =.0166, respectively). Plasma MMP-9 levels decreased, and TIMP-1 levels increased after treatment (P =.035 and P =.005, respectively). Levels of MMP-9 correlated with CHD risk (r = 0.317, P =.007) and HDL cholesterol (r = -0.237, P =.022), but not CVA risk. There were no significant correlations between TIMP-1 and CVA or CHD scores. Increased circulating MMP-9 and TIMP-1 at baseline in patients with hypertension could reflect an increased deposition and retention of type I collagen at the expense of other components of ECM within the cardiac and vascular ECM. After cardiovascular risk management, MMP-9 levels decreased and TIMP-1 levels increased. Elevated levels of MMP-9 also appeared to be associated with higher Framingham cardiovascular risk scores. Our observations suggest a possible role for these surrogate markers of tissue ECM composition and the prognosis of cardiovascular events in hypertension.


Unsaturated fatty acids are the active molecules of a glucan-synthase-inhibitory fraction isolated from entomophthoralean protoplasts.
A few entomophthoralean species are able to multiply in a protoplast form. The polysaccharide synthases which synthesize the cell wall are inactivated in this form. An inhibitor of one of the key enzymes of wall synthesis, glucan synthase, was isolated from entomophthoralean protoplasts, using silica column chromatography and HPLC. Thin-layer and gas chromatography revealed free fatty acids in the inhibitory fractions. These fatty acids, including long-chain unsaturated fatty acids, were shown to be responsible for the inhibition of glucan synthase. The fatty acids were generated during incubation of a protoplast homogenate for 36 h at 37 degrees C and were shown to be non-competitive and non-specific inhibitors of glucan synthase.


High Colonization Possibility of Some Species of Weeds in Suaeda salsa Community: From an Ecological Stoichiometry Perspective.
Suaeda salsa community is a vegetation type in saline-alkali areas. Weed invasion and colonization in S. salsa communities lead to fragmentationsof S. salsa communities. The colonization of invaded weeds in S. salsa communities is related to community succession of saline-alkali zones. The fragmented S. salsa community may be restored if the mechanism of invaded weed colonization in S. salsa communities is clearly elucidated. Thus, we studied the ecological stoichiometric characteristics of soils and plants in a salt marsh to explain the high colonization possibility of invaded weeds in S. salsa communities. In October 2014, soils and plants were collected from Dongfeng Salt Marsh, Jiaozhou Bay, Shandong Province, China. The ratio of Ex-N/Ex-P in soil was less than 13, which suggests a relative nitrogen limitation for the primary production in the zone. The minimum phosphorus content in plants was higher than 1 mg g-1, whereas the maximum nitrogen content in plants was less than 13 mg g-1. These results imply that phosphorus was abundant, whereas nitrogen was deficient in the area. The plants in the salt marsh may be limited by nitrogen. Given the relatively lower nitrogen contents in Cyperus glomeratus, Echinochloa crusgalli, and Aster subulatus than that in S. salsa, these three species exhibited higher competitiveness than S. salsa did when nitrogen was limited in primary production. These weed species may colonize highly in S. salsa communities. Moreover, nitrogen fertilization might be effective to maintain S. salsa community in Dongfeng Salt Marsh, whereas its effects on controlling weeds colonization in S. salsa communities need more studies to verify.


Transcriptomic and microRNAomic profiling reveals multi-faceted mechanisms to cope with phosphate stress in a dinoflagellate.
Although gene regulation can occur at both transcriptional and epigenetic (microRNA) levels, combined transcriptomic and microRNAomic responses to environmental stress are still largely unexplored for marine plankton. Here, we conducted transcriptome and microRNAome sequencing for Prorocentrum donghaiense to understand the molecular mechanisms by which this dinoflagellate copes with phosphorus (P) deficiency. Under P-depleted conditions, G1/S specific cyclin gene was markedly downregulated, consistent with growth inhibition, and genes related to dissolved organic phosphorus (DOP) hydrolysis, carbon fixation, nitrate assimilation, glycolysis, and cellular motility were upregulated. The elevated expression of ATP-generating genes (for example, rhodopsin) and ATP-consuming genes suggests some metabolic reconfiguration towards accelerated ATP recycling under P deficiency. MicroRNAome sequencing revealed 17 microRNAs, potentially regulating 3268 protein-coding genes. Functional enrichment analysis of these microRNA-targeted genes predicted decreases in sulfatide (sulfolipid) catabolism under P deficiency. Strikingly, we detected a significant increase in sulfolipid sulfatide content (but not in sulphoquinovosyldiacylglycerol content) and its biosynthesis gene expression, indicating a different sulfolipid-substituting-phospholipid mechanism in this dinoflagellate than other phytoplankters studied previously. Taken together, our integrative transcriptomic and microRNAomic analyses show that enhanced DOP utilization, accelerated ATP cycling and repressed sulfolipid degradation constitute a comprehensive strategy to cope with P deficiency in a model dinoflagellate.


5-(Pentafluorobenzoylamino)fluorescein: A selective substrate for the determination of glutathione concentration and glutathione S-transferase activity.
5-(Pentafluorobenzoylamino)fluorescein (PFB-F), a new thiol-reactive molecule was synthesized to improve the detection limits and specificity of the assays for glutathione S-transferase (GST) activity and glutathione (GSH). A rapid assay method to measure GSH concentration or GST activity and the simultaneous analysis of multiple samples is possible because the glutathione adduct, GS-TFB-F, is separated from PFB-F by thin-layer chromatography (TLC) and can be quantitated by a fluorescence scanner. The detection limits for GSH and for GST activity using TLC were found to be as low as 10 pmol/microl and 1 ng/microl using equine liver GST, respectively. Determination of GSH concentration or GST activity in bovine pulmonary artery endothelial (BPAE) cell lysates gave a linear response for samples corresponding to 500-2500 cells. PFB-F could also measure GST activities of GST fusion proteins and prove to be a suitable substrate for determining the activities of human GST isozymes and other sources of mammalian GST. The selectivity of PFB-F with GSH was proven by comparing trace amount of the adducts that formed with cysteine and beta-galactosidase to that formed with GSH. The HPLC profile of a reaction mixture where cell lysate was used in place of purified GST, also shows only two main peaks, corresponding to GS-TFB-F and unreacted PFB-F. The selectivity of PFB-F for GSH was further confirmed by exposing BPAE cells to dl-buthionine-[S,R]-sulfoximine (BSO). Our results of GS-TFB-F determination indicate that 12-, 24-, or 36-h incubations with BSO caused 2-, 6-, or 7.6-fold reductions in GSH levels, respectively.


Serial assembly of Thermus megaplasmid DNA in the genome of Bacillus subtilis 168: a BAC-based domino method applied to DNA with a high GC content.
Bacillus subtilis is the only bacterium-based host able to clone giant DNA above 1000 kbp. DNA previously handled by this host was limited to that with GC content similar to or lower than that of the B. subtilis genome. To expand the target DNA range to higher GC content, we tried to clone a pTT27 megaplasmid (257 kbp, 69% of G+C) from Thermus thermophilus. To facilitate the reconstruction process, we subcloned pTT27 in a bacterial artificial chromosome (BAC) vector of Escherichia coli. Owing to the ability of BAC to carry around 100 kbp DNA, only 4 clones were needed to cover the pTT27 and conduct step-by-step assembly in the B. subtilis genome. The full length of 257 kbp was reconstructed through 3 intermediary lengths (108, 153, and 226 kbp), despite an unexpected difficulty in the maintenance of DNA >200 kbp. Retrieval of these four pTT27 segments from the B. subtilis genome by genetic transfer to a plasmid pLS20 was attempted. A stable plasmid clone was obtained only for the 108 and 153 kbp intermediates. The B. subtilis genome was demonstrated to accommodate large DNA with a high GC content, but may be restricted to less than 200 kbp by unidentified mechanisms.


Physical Activity Protects the Human Brain against Metabolic Stress Induced by a Postprandial and Chronic Inflammation.
In recent years, it has become clear that chronic systemic low-grade inflammation is at the root of many, if not all, typically Western diseases associated with the metabolic syndrome. While much focus has been given to sedentary lifestyle as a cause of chronic inflammation, it is less often appreciated that chronic inflammation may also promote a sedentary lifestyle, which in turn causes chronic inflammation. Given that even minor increases in chronic inflammation reduce brain volume in otherwise healthy individuals, the bidirectional relationship between inflammation and sedentary behaviour may explain why humans have lost brain volume in the last 30,000 years and also intelligence in the last 30 years. We review evidence that lack of physical activity induces chronic low-grade inflammation and, consequently, an energy conflict between the selfish immune system and the selfish brain. Although the notion that increased physical activity would improve health in the modern world is widespread, here we provide a novel perspective on this truism by providing evidence that recovery of normal human behaviour, such as spontaneous physical activity, would calm proinflammatory activity, thereby allocating more energy to the brain and other organs, and by doing so would improve human health.


Autophagy was involved in the protective effect of metformin on hyperglycemia-induced cardiomyocyte apoptosis and Connexin43 downregulation in H9c2 cells.
Background: Increased cardiomyocyte apoptosis under high glucose condition contributes to diabetic cardiomyopathy. Degradation of cardiac Connexin43 (Cx43) has been associated with cardiac dysfunction in diabetic heart. Clinical and experimental studies suggested that metformin (Met) exhibits cardioprotective properties against diabetes. Aim: The aim of this study was to investigate the effect and underlying signaling mechanisms of metformin on apoptosis and Cx43 expression in H9c2 cells presenting with hyperglycemia conditions. Methods: In the present study, H9c2 cardiac cells were incubated with 5.5 mM glucose, 33.3 mM glucose, 33.3 mM glucose with metformin at two dose (100 μM, 1 mM) for 96 hours, and 1 mM metformin with chloroquine (50 μM) in 33.3 mM glucose medium. Cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell survival assay. Cytotoxicity was determined by the release of lactate dehydrogenase (LDH). The expression of Cx43, autophagic maker protein (LAMP-1, Beclin-1, p62 and LC3) and apoptosis maker protein (Bcl-2 and Bax) were determined by western blot. Results: The results showed that high glucose increased apoptosis and decreased Cx43 expression. Interestingly, metformin attenuated hyperglycemia-increased apoptosis and restored Cx43 expression. Moreover, this treatment caused autophagy as well, which indicated by up-regulation of autophagy-related proteins LAMP-1, Beclin-1, p62 and reduction in the ratio of LC3-II/LC3-I. In addition, administration autophagy inhibitor chloroquine (CQ) did not block the effect of metformin on Cx43 expression while increasing Cx43 content, together with an increased apoptosis. Conclusion: Administration metformin can protect the H9c2 cells against hyperglycemia-induced apoptosis and Cx43 down-regulation, in part, mediated through the induction of autophagy pathway.


Design of superresolving continuous phase filters.
We present a procedure for designing to control the three-dimensional light-intensity distribution near focus. Our method is based on the use of a series of figures of merit that are properly defined to describe the effect of general complex pupil functions. As a practical implementation, we have applied our method to obtain super resolving continuous smoothly varying phase-only filters. The advantages of these kinds of filters are that they do not produce energy absorption and they are easy to build with a phase-controlling device such as a deformable mirror. Results of comparisons between the performance of our method and that of other phase-filter designs are provided.


Tropomyosin 3 expression leads to hypercontractility and attenuates myofilament length-dependent Ca(2+) activation.
Tropomyosin (TM), an integral component of the thin filament, is encoded by three striated muscle isoforms: alpha-TM, beta-TM, and TPM 3. Although the alpha-TM and beta-TM isoforms are well characterized, less is known about the function of the TPM 3 isoform, which is predominantly found in the slow-twitch musculature of mammals. To determine its functional significance, we ectopically expressed this isoform in the hearts of transgenic mice. We generated six transgenic mouse lines that produce varying levels of TPM 3 message with ectopic TPM 3 protein accounting for 40-60% of the total striated muscle tropomyosin. The transgenic mice have normal life spans and exhibit no morphological abnormalities in their sarcomeres or hearts. However, there are significant functional alterations in cardiac performance. Physiological assessment of these mice by using closed-chest analyses and a work-performing model reveals a hyperdynamic effect on systolic and diastolic function. Analysis of detergent-extracted fiber bundles demonstrates a decreased sensitivity to Ca(2+) in force generation and a decrease in length-dependent Ca(2+) activation with no detectable change in interfilament spacing as determined by using X-ray diffraction. Our data are the first to demonstrate that TM isoforms can affect sarcomeric performance by decreasing sensitivity to Ca(2+) and influencing the length-dependent Ca(2+) activation.


Aortic calcification is associated with arterial stiffening, left ventricular hypertrophy, and diastolic dysfunction in elderly male patients with hypertension.
Stiffening of large arteries can result in changes of cardiac structure and function by increasing afterload to the left ventricle. Calcification has been proposed as a mechanism underlying progression of arterial stiffening. The aim of the current study was to investigate the relationship between aortic calcification, arterial stiffening, left ventricular hypertrophy, and diastolic dysfunction. One hundred and sixty-four hypertensive elderly (≥65 years old) male patients with normal left ventricular systolic function (left ventricular ejection fraction ≥55%) underwent transthoracic echocardiography, brachial-ankle pulse wave velocity (baPWV), and noncontrast computed tomography. Coronary artery calcium score and aorta calcium score (ACS) were measured on noncontrast computed tomography using the volume method. Left ventricular dimensions, mitral inflow velocities, and early mitral annular (E') velocity were measured using transthoracic echocardiography. The left ventricular mass index (LVMI) was calculated. The logACS was associated with mean baPWV (r = 0.387, P = 0.001), LVMI (r = 0.241, P < 0.002), E' velocity (r = -0.293, P < 0.001), and E/E' (r = 0.194, P = 0.013), suggesting arterial stiffening, increased left ventricular mass, and diastolic dysfunction in patients with raised ACS. On multivariate analysis, the LVMI showed an independent positive association with the logACS, even after adjusting for various clinical variables and the coronary artery calcium score (P = 0.009). Similarly, E' velocity also demonstrated an independent negative association with the logACS on multivariate analysis (P = 0.003). The mean baPWV, LVMI, and E' velocity showed similar correlations with both thoracic and abdominal ACS, even when thoracic and abdominal calcium scores were calculated separately. Heavy aortic calcification and resultant arterial stiffening might underlie left ventricular hypertrophy and diastolic dysfunction in elderly male patients with hypertension.


p53-dependent repression of polo-like kinase-1 (PLK1).
PLK1 is a critical mediator of G₂/M cell cycle transition that is inactivated and depleted as part of the DNA damage-induced G₂/M checkpoint. Here we show that downregulation of PLK1 expression occurs through a transcriptional repression mechanism and that p53 is both necessary and sufficient to mediate this effect. Repression of PLK1 by p53 occurs independently of p21 and of arrest at G₁/S where PLK1 levels are normally repressed in a cell cycle-dependent manner through a CDE/CHR element. Chromatin immunoprecipitation analysis indicates that p53 is present on the PLK1 promoter at two distinct sites termed p53RE1 and p53RE2. Recruitment of p53 to p53RE2, but not to p53RE1, is stimulated in response to DNA damage and/or p53 activation and is coincident with repression-associated changes in the chromatin. Downregulation of PLK1 expression by p53 is relieved by the histone deacetylase inhibitor, trichostatin A, and involves recruitment of histone deacetylase to the vicinity of p53RE2, further supporting a transcriptional repression mechanism. Additionally, wild type, but not mutant, p53 represses expression of the PLK1 promoter when fused upstream of a reporter gene. Silencing of PLK1 expression by RNAi interferes with cell cycle progression consistent with a role in the p53-mediated checkpoint. These data establish PLK1 as a direct transcriptional target of p53, independently of p21, that is required for efficient G₂/M arrest.


The effect of pH on the growth and motility of Rhodobacter sphaeroides WS8 and the nature of the driving force of the flagellar motor.
Rhodobacter sphaeroides WS8 grew, and swam vigorously, over the pH range 6 to 9. Sustained motility was, however, observed in populations of cells resuspended at pH values between 4.9 and 10.4, although the mean run speed was reduced at the extremes of pH. The ability of R. sphaeroides to swim in strong alkaline conditions prompted the question of whether motility at alkaline pH was powered by a sodium motive force, as has been found in the facultative alkalophilic Bacillus and Vibrio species, particularly as motility was found to be sensitive to the sodium channel inhibitor amiloride. The nature of the driving force of the flagellar motor was therefore investigated. It was found that R. sphaeroides was motile over the same pH range in the absence and presence of sodium ions. The protonophore CCCP was found to inhibit motility under all conditions, whereas monensin, an inhibitor of sodium pumps, had no effect upon motility in the presence or absence of sodium. It was concluded that the delta p is the driving force for the flagellar motor in R. sphaeroides at all values of pH. Amiloride, a specific inhibitor of the sodium-driven flagellar motor in alkalophilic Bacillus and Vibrio was shown to act non-specifically on the proton driven motor of R. sphaeroides, reducing the swimming speed of this organism in media with and without sodium to the same extent and over the complete pH range. Measurement of the delta p by using the electrochromic absorbance change of the carotenoid pigments to measure delta psi and 31P-NMR to measure delta pH showed that the maximum delta p was about -215 mV. At pH 10 the cells swam more slowly and the delta p was about -90 mV. These data suggest that the flagellar motor of R. sphaeroides is proton-driven under all conditions with a threshold for motor rotation below -90 mV and saturation at above -90 mV and below -215 mV.


Crystal structure of prunin-1, a major component of the almond (Prunus dulcis) allergen amandin.
Seed storage proteins are accumulated during seed development and act as a reserve of nutrition for seed germination and young sprout growth. Plant seeds play an important role in human nutrition by providing a relatively inexpensive source of protein. However, many plant foods contain allergenic proteins, and the number of people suffering from food allergies has increased rapidly in recent years. The 11S globulins are the most widespread seed storage proteins, present in monocotyledonous and dicotyledonous seeds as well as in gymnosperms (conifers) and other spermatophytes. This family of proteins accounts for a number of known major food allergens. They are of interest to both the public and industry due to food safety concerns. Because of the interests in the structural basis of the allergenicity of food allergens, we sought to determine the crystal structure of Pru1, the major component of the 11 S storage protein from almonds. The structure was refined to 2.4 A, and the R/Rfree for the final refined structure is 17.2/22.9. Pru1 is a hexamer made of two trimers. Most of the back-to-back trimer-trimer association was contributed by monomer-monomer interactions. An alpha helix (helix 6) at the C-terminal end of the acidic domain of one of the interacting monomers lies at the cleft of the two protomers. The residues in this helix correspond to a flexible region in the peanut allergen Ara h 3 that encompasses a previously defined linear IgE epitope.


Application of the Goldilocks effect to the design of potent and selective inhibitors of phenylethanolamine N-methyltransferase: balancing pKa and steric effects in the optimization of 3-methyl-1,2,3,4-tetrahydroisoquinoline inhibitors by beta-fluorination.
3-Methyl-1,2,3,4-tetrahydroisoquinolines (3-methyl-THIQs) are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT), but are not selective due to significant affinity for the alpha(2)-adrenoceptor. Fluorination of the methyl group lowers the pK(a) of the THIQ amine from 9.53 (CH(3)) to 7.88 (CH(2)F), 6.42 (CHF(2)), and 4.88 (CF(3)). This decrease in pK(a) results in a reduction in affinity for the alpha(2)-adrenoceptor. However, increased fluorination also results in a reduction in PNMT inhibitory potency, apparently due to steric and electrostatic factors. Biochemical evaluation of a series of 3-fluoromethyl-THIQs and 3-trifluoromethyl-THIQs showed that the former were highly potent inhibitors of PNMT, but were often nonselective due to significant affinity for the alpha(2)-adrenoceptor, while the latter were devoid of alpha(2)-adrenoceptor affinity, but also lost potency at PNMT. 3-Difluoromethyl-7-substituted-THIQs have the proper balance of both steric and pK(a) properties and thus have enhanced selectivity versus the corresponding 3-fluoromethyl-7-substituted-THIQs and enhanced PNMT inhibitory potency versus the corresponding 3-trifluoromethyl-7-substituted-THIQs. Using the "Goldilocks Effect" analogy, the 3-fluoromethyl-THIQs are too potent (too hot) at the alpha(2)-adrenoceptor and the 3-trifluoromethyl-THIQs are not potent enough (too cold) at PNMT, but the 3-difluoromethyl-THIQs are just right. They are both potent inhibitors of PNMT and highly selective due to low affinity for the alpha(2)-adrenoceptor. This seems to be the first successful use of the beta-fluorination of aliphatic amines to impart selectivity to a pharmacological agent while maintaining potency at the site of interest.


Cost-effectiveness of transforaminal lumbar interbody fusion for Grade I degenerative spondylolisthesis.
Transforaminal lumbar interbody fusion (TLIF) for spondylolisthesis-associated back and leg pain is associated with improvement in pain, disability, and quality of life. However, given the rising health care costs associated with spinal fusion procedures and varying results of recent cost-utility studies, the cost-effectiveness of TLIF remains unclear. The authors set out to assess the comprehensive costs of TLIF at their institution and to determine its cost-effectiveness in the treatment of degenerative spondylolisthesis. Forty-five patients undergoing TLIF for Grade I degenerative spondylolisthesis-associated back and leg pain after 6-12 months of conservative therapy were included. The authors assessed the 2-year back pain visual analog scale (VAS) score, leg pain VAS score, Oswestry Disability Index, and total back-related medical resource utilization, missed work, and health-state values (quality-adjusted life years [QALYs], calculated from EQ-5D with US valuation). Two-year resource use was multiplied by unit costs based on Medicare national allowable payment amounts (direct cost), and patient and caregiver workday losses were multiplied by the self-reported gross-of-tax wage rate (indirect cost). The mean total 2-year cost per QALY gained after TLIF was assessed. Compared with preoperative health states reported after at least 6 months of medical management, a significant improvement in back pain VAS score, leg pain VAS score, and Oswestry Disability Index was observed 2 years after TLIF, with a mean 2-year gain of 0.86 QALYs. The mean ± SD total 2-year cost of TLIF was $36,836 ± $11,800 (surgery cost, $21,311 ± $2800; outpatient resource utilization cost, $3940 ± $2720; indirect cost, $11,584 ± $11,363). Transforaminal lumbar interbody fusion was associated with a mean 2-year cost per QALY gained of $42,854. Transforaminal lumbar interbody fusion improved pain, disability, and quality of life in patients with degenerative spondylolisthesis-associated back and leg pain. The total cost per QALY gained for TLIF was $42,854 when evaluated 2 years after surgery with Medicare fees, suggesting that TLIF is a cost-effective treatment of lumbar spondylolisthesis.


Mortality after inpatient treatment for diarrhea in children: a cohort study.
There is an increasing recognition that children remain at elevated risk of death following discharge from health facilities in resource-poor settings. Diarrhea has previously been highlighted as a risk factor for post-discharge mortality. A retrospective cohort study was conducted to estimate the incidence and demographic, clinical, and biochemical features associated with inpatient and 1-year post-discharge mortality amongst children aged 2-59 months admitted with diarrhea from 2007 to 2015 at Kilifi County Hospital and who were residents of Kilifi Health and Demographic Surveillance System (KHDSS). Log-binomial regression was used to identify risk factors for inpatient mortality. Time at risk was from the date of discharge to the date of death, out-migration, or 365 days later. Post-discharge mortality rate was computed per 1000 child-years of observation, and Cox proportion regression used to identify risk factors for mortality. Two thousand six hundred twenty-six child KHDSS residents were admitted with diarrhea, median age 13 (IQR 8-21) months, of which 415 (16%) were severely malnourished and 130 (5.0%) had a positive HIV test. One hundred twenty-one (4.6%) died in the hospital, and of 2505 children discharged alive, 49 (2.1%) died after discharge: 21.4 (95% CI 16.1-28.3) deaths per 1000 child-years. Admission with signs of both diarrhea and severe pneumonia or severe pneumonia alone had a higher risk of both inpatient and post-discharge mortality than admission for diarrhea alone. There was no significant difference in inpatient and post-discharge mortality between children admitted with diarrhea alone and those with other diagnoses excluding severe pneumonia. HIV, low mid-upper arm circumference (MUAC), and bacteremia were associated with both inpatient and post-discharge mortality. Signs of circulatory impairment, sepsis, and abnormal electrolytes were associated with inpatient but not post-discharge mortality. Prior admission and lower chest wall indrawing were associated with post-discharge mortality but not inpatient mortality. Age, stuntedness, and persistent or bloody diarrhea were not associated with mortality before or after discharge. Our results accentuate the need for research to improve the uptake and outcomes of services for malnutrition and HIV as well as to elucidate causal pathways and test interventions to mitigate these risks.


1Hepatitis C virus NS5A protein modulates c-Jun N-terminal kinase through interaction with tumor necrosis factor receptor-associated factor 2.
The nonstructural 5A (NS5A) protein of hepatitis C virus (HCV) is a phosphoprotein possessing various functions. We have previously reported that the HCV NS5A protein interacts with tumor necrosis factor (TNF) receptor-associated factor (TRAF) domain of TRAF2 (Park, K.-J., Choi, S.-H., Lee, S. Y., Hwang, S. B., and Lai, M. M. C. (2002) J. Biol. Chem. 277, 13122-13128). Both TNF-alpha- and TRAF2-mediated nuclear factor-kappaB (NF-kappaB) activations were inhibited by NS5A-TRAF2 interaction. Because TRAF2 is required for the activation of both NF-kappaB and c-Jun N-terminal kinase (JNK), we investigated HCV NS5A protein for its potential capacity to modulate TRAF2-mediated JNK activity. Using in vitro kinase assay, we have found that NS5A protein synergistically activated both TNF-alpha- and TRAF2-mediated JNK in human embryonic kidney 293T cells. Furthermore, synergism of NS5A-mediated JNK activation was inhibited by dominant-negative form of MEK kinase 1. Our in vivo binding data show that NS5A does not inhibit interaction between TNF receptor-associated death domain and TRAF2 protein, indicating that NS5A and TRAF2 may form a ternary complex with TNF receptor-associated death domain. These results indicate that HCV NS5A protein modulates TNF signaling of the host cells and may play a role in HCV pathogenesis.


Diminished bone strength is observed in adult women and men who sustained a mild trauma distal forearm fracture during childhood.
Children and adolescents who sustain a distal forearm fracture (DFF) owing to mild, but not moderate, trauma have reduced bone strength and cortical thinning at the distal radius and tibia. Whether these skeletal deficits track into adulthood is unknown. Therefore, we studied 75 women and 75 men (age range, 20 to 40 years) with a childhood (age < 18 years) DFF and 150 sex-matched controls with no history of fracture using high-resolution peripheral quantitative computed tomography (HRpQCT) to examine bone strength (ie, failure load) by micro-finite element (µFE) analysis, as well as cortical and trabecular bone parameters at the distal radius and tibia. Level of trauma (mild versus moderate) was assigned using a validated classification scheme, blind to imaging results. When compared to sex-matched, nonfracture controls, women and men with a mild trauma childhood DFF (eg, fall from standing height) had significant reductions in failure load (p < 0.05) of the distal radius, whereas women and men with a moderate trauma childhood DFF (eg, fall while riding a bicycle) had values similar to controls. Consistent findings were observed at the distal tibia. Furthermore, women and men with a mild trauma childhood DFF had significant deficits in distal radius cortical area (p < 0.05), and significantly lower dual-energy X-ray absorptiometry (DXA)-derived bone density at the radius, hip, and total body regions compared to controls (all p < 0.05). By contrast, women and men with a moderate trauma childhood DFF had bone density, structure, and strength that did not differ significantly from controls. These findings in young adults are consistent with our observations in children/adolescents with DFF, and they suggest that a mild trauma childhood DFF may presage suboptimal peak bone density, structure, and strength in young adulthood. Children and adolescents who suffer mild trauma DFFs may need to be targeted for lifestyle interventions to help achieve improved skeletal health.


Methods of ammonia removal in anaerobic digestion: a review.
The anaerobic digestion of substrates with high ammonia content has always been a bottleneck in the methanisation process of biomasses. Since microbial communities in anaerobic digesters are sensitive to free ammonia at certain conditions, the digestion of nitrogen-rich substrates such as livestock wastes may result in inhibition/toxicity eventually leading to process failures, unless appropriate engineering precautions are taken. There are many different options reported in literature to remove ammonia from anaerobic digesters to achieve a safe and stable process so that along with high methane yields, a good quality of effluents can also be obtained. Conventional techniques to remove ammonia include physical/chemical methods, immobilization and adaptation of microorganisms, while novel methods include ultrasonication, microwave, hollow fiber membranes and microbial fuel cell applications. This paper discusses conventional and novel methods of ammonia removal from anaerobic digesters using nitrogen-rich substrates, with particular focus on recent literature available about this topic.


Ultraviolet phototoxicity of upconversion nanoparticles illuminated with near-infrared light.
Recently introduced upconversion nanoparticles (UCNPs) have pushed the depth of photodynamic therapy (PDT) treatment to the centimetre range by converting deeply-penetrating near-infrared (NIR) radiation to visible radiation for photoexcitation of PDT drugs. Here we demonstrate that the direct exposure of the cancer tissue to phototoxic ultraviolet radiation generated by NIR-photoexcited UCNPs enabled successful PDT. To this aim, core/shell UCNPs of the formula NaYF4:Yb3+Tm3+/NaYF4 featuring an enhanced band in the ultraviolet UV-A and UV-B spectral bands were rationally designed and synthesised. Coupling UCNPs to the recombinant modules of the Designed Ankyrin Repeat Protein (DARPin) fused to a fluorescent protein mCherry allowed the target delivery of DARPin-mCherry/UCNP to human breast adenocarcinoma SK-BR-3 cells overexpressing HER2/neu receptors, as confirmed by fluorescence microscopy. DARPin-mCherry/UCNPs were demonstrated to be phototoxic to SK-BR-3 cells under 975 nm laser irradiation at a dose of 900 J cm-2 due to the UV photoexcitation of endogenous photosensitizers and concomitant generation of reactive oxygen species. The Lewis lung cancer mouse model was employed to demonstrate the feasibility of PDT using UCNP-mediated UV excitation of endogenous photosensitizers in the tumor tissue at a NIR dose of 1200 J cm-2. This study paves the way for exploring and harnessing UV photoexcitation processes in deep tissues in vivo.


Standardized care plans in Swedish health care: their quality and the extent to which they are used.
To investigate the quality of standardized care plans and the extent to which they are used within Swedish in-hospital somatic care. Further, to examine the quality of the knowledge summaries on which existing standardized care plans were supposed to be based. Submitted documents were reviewed with study-specific protocols. A national survey, based on a structured selection of Swedish hospitals. A total of 25 Swedish hospitals participated, and were asked to submit all documents in use that were labelled standardized care plan. Only 4% (34 out of 782) of the reviewed documents fulfilled the criteria for being a standardized care plan. None of the 34 knowledge summaries (an accompanying document with a compilation of scientific facts and reliable experience) was evidence-based. There is a lack of knowledge regarding what a standardized care plan is, and how such a document should emanate from evidence-based knowledge. Our results raise the question of how recent developments in research are used to create standardized care plans for the best possible care. In the process of developing standardized care plans it is important to acknowledge that staff who develop these plans need scientific training and experience. Standardized care plans are in the early stages of development, and at this stage it seems appropriate to initiate a discussion regarding possible cooperation at national level when developing standardized care plans for certain large groups of patients suffering from specific diseases, or undergoing the same treatment.


Relationship between chronotype and consumption of stimulants.
Consumption of some stimulants may lead to health problems. The aim of the study was to identify a potential correlation between extreme chronotypes and the tendency to use various stimulants. The preferred time of consumption was also checked, both on working and nonworking days. The study was conducted in January 2020 using the CAWI method. 306 people took part in the survey. To determine the chronotype of the surveyed people, the polish version of MEQ questionnaire (Morningness - Eveningness Questionnaire) was used. Because 178 respondents were intermediate types, 128 people participated in the second part of the study, including 68 owls and 60 larks. Activity preferences during the day of respondents were checked and compared with data about the quantity and frequency of using stimulants like coffee, energy drinks, alcohol and cigarettes. Chi-square test was used for testing relationships. The time periods for taking stimulants differed between groups and were associated with activity during the day. It has been shown that people with evening chronotype use more energy drinks (p = .009), alcohol drinks (p = .013) and cigarettes or e-cigarettes (p = .021), especially in the group of respondents aged ≥30. Social jet lag was statistically higher in the group of owls and larks; however, consumption of stimulants depended on age and chronotype, not social jet lag. People with the morning chronotype are less likely to use stimulants. Owls showed a greater and more frequent use of energy drinks, alcohol and cigarettes, especially those older than 30 years. Assessing eveningness among people aged more than 30 may be helpful in characterizing an overall risk profile.


Alterations in C3, C4, factor B, and related metabolites in septic shock.
Forty subjects consisting of (i) patients with septic shock, (ii) patients with sepsis without shock, (iii) critically ill non-septic patients, and (iv) normal controls were studied for plasma C3, C4, factor B, iC3b, C4d, Bb, and SC5b-9 levels in an attempt to profile the pattern of complement activation in sepsis. Significant decreases in plasma C3 and C4 concentrations were observed in septic shock patients compared to normal as well as to critically ill subjects. When adjusted for illness severity, levels of C3 but not C4 showed significant differences between septic shock and critically ill patients. Concentrations of the complement metabolite Bb as well as the Bb to factor B ratio were significantly increased in septic shock patients. SC5b-9 levels were significantly higher in septic shock patients compared to normal as well as to critically ill subjects. No increases in C4d or iC3b were observed, but the iC3b to C3 ratio was higher in septic shock patients compared to that in normal subjects. In septic shock patients, there were significant correlations between SC5b-9 and Bb (P = 0.0213) concentrations and between C3 and Factor B concentrations (P = 0.0041). SC5b-9 levels also were correlated with lactate levels in septic shock patients (P = 0.0091). These findings demonstrate a metabolite pattern consistent with primarily alternative and terminal pathway activation in septic shock patients. Decreases in C4, a classical pathway component, may not be specific for septic shock and do not appear to be necessarily due to significant complement consumption/activation.


rRNA distribution during microspore development in anthers of Beta vulgaris L. quantitative in situ hybridization analysis.
We related changes in the ultrastructural organization of the nucleoli with the results of quantitative in situ hybridizations to characterize rRNA metabolism during the development of microspore mother cells in the sugar beet anther (Beta vulgaris L.). In the course of meiotic prophase and early postmeiotic interphase the morphological characteristics of the nucleoli are typical of low or no transcriptional activity and a low rate of rRNA processing. However, we found evidence of an apparent increase in the relative numbers of 18 S rRNA transcripts in some stages of microsporogenesis. This was found in both the nucleoli and cytoplasm of pachytene meiocytes, and in later stages there was a spectacular accumulation of rRNA transcripts in nucleoli of the tetrad cells. Quantitative data are analyzed in the light of morphometric findings in the cell and their compartments to elucidate the degree to which changes in cell size are related to changes in labeling density and distribution. The results are discussed in terms of rRNA synthesis, transport and degradation as processes involved in the regulation of rRNA within microsporocytes and microspores.


Induced abortion, contraceptive use, and dual protection among female sex workers in Moscow, Russia.
To describe abortion history and current contraceptive use among female sex workers (FSWs) in Moscow, Russia. A clinic-based survey was conducted among 147 FSWs in Moscow during an 8-month period in 2005. In total, 83 of 143 (58.0%) FSWs reported a history of abortion, with 45 of 143 (31.5%) indicating multiple abortions. Condoms were the primary form of contraception (145/146 [99.3%]); just 17 of 142 (12.0%) FSWs reported using non-barrier modern contraception. All women who reported using a non-barrier modern method also indicated condom use (i.e. dual protection). Non-barrier contraceptive use was associated with inconsistent condom use (odds ratio [OR] 3.10; 95% confidence interval [CI], 1.07-9.02) and multiple abortions (OR 4.71; 95% CI, 1.19-18.62). The results illustrate substantial risk for unintended pregnancy among FSWs. Further research is needed regarding the dynamics of non-barrier contraception and condom use. Efforts to improve the health and wellbeing of FSWs should include access to safe and effective contraception, in addition to HIV prevention.


Perceived risk of medicine side effects in users of a patient information website: a study of the use of verbal descriptors, percentages and natural frequencies.
Research into the provision of patient information has demonstrated that, under certain conditions, patients overestimate the risks of medicine side effects. Gigerenzer and Edwards (2004) argue that 'natural frequencies' are a less confusing way of expressing risk information. Two experiments with users of an existing high profile patient information website, investigate the effectiveness of presenting medicine side-effect risk information in different forms. In both experiments participants were randomly allocated to one of the three conditions for representing risk information (a form of 'natural frequency', percentages and verbal descriptors). Participants were recruited from users of the Cancer Research UK patient information website (Cancer Help UK). In Experiment 1, participants (N=148) were asked to imagine that they had to take a chemotherapy drug (Taxol) and were asked to estimate the risks of two side-effects occurring. In Experiment 2 participants (N=137) estimated the risk for three different side-effects occurring with the painkiller ibuprofen. In both experiments, verbal descriptions led to significantly higher estimations of risk compared to the other two formats. There was some evidence that people given information as frequencies were more accurate in their estimates than those given percentage information. These findings provide partial support for the advantages of a form of 'natural frequencies' when presenting side-effects to patients. They also add weight to the growing body of research highlighting the deficiencies in using verbal descriptions of side-effect risk alone.


Outcomes of noninvasive ventilation in acute hypoxemic respiratory failure in a respiratory intensive care unit in north India.
To determine the outcomes of noninvasive ventilation (NIV) and the factors associated with NIV failure in patients with acute hypoxemic respiratory failure (AHRF). This was a prospective observational study and all patients with AHRF requiring NIV over a one-and-a-half-year period were enrolled in the study. We recorded the etiology of AHRF and prospectively collected the data for heart rate, respiratory rate, arterial blood gases (pH, P(aO2), P(aCO2)) at baseline, 1 hour, and 4 hours. The patients were further classified into 2 groups, based on the etiology of AHRF: either acute lung injury/acute respiratory distress syndrome [ALI/ARDS], or AHRF due to other causes. The primary outcome was the need for endotracheal intubation during the ICU stay. During the study period, 287 patients were admitted in the ICU, and of these 40 (13.9%) (21 ALI/ARDS, 19 AHRF due to other causes; 16 male, 24 female patients; mean +/- SD age 43.2 +/- 20.6 years) patients with AHRF were initiated on NIV. The baseline characteristics were similar in the 2 groups. After 1 hour there was a significant decrease in respiratory rate and heart rate, with increase in pH and P(aO2); however, there was no difference in improvement of clinical and blood-gas parameters between the 2 groups. The NIV failures, the mean ICU and hospital stay, and the hospital mortality were similar in the 2 groups. In the univariate logistic regression model the only factor associated with NIV failure was the baseline ratio of P(aO2) to fraction of inspired oxygen (P(aO2)/F(IO2)) (odds ratio 0.97, 95% confidence interval 0.95-0.99). NIV should be judiciously used in patients with AHRF. A low baseline P(aO2)/F(IO2) ratio was associated with NIV failure.


Impact of Quality Bundle Enforcement by a Critical Care Pharmacist on Patient Outcome and Costs.
Surgical and medical ICU patients are at high risk of mortality and provide a significant cost to the healthcare system. The aim of this study is to describe the effect of pharmacist-led interventions on drug therapy and clinical strategies on ICU patient outcome and hospital costs. Before and after study in two French ICUs (16 and 10 beds). ICU patients. From January 1, 2013, to June 30, 2015, a pharmacist observation period was compared with an intervention period in which a critical care pharmacist provided recommendations to clinicians regarding sedative drugs and doses, choice of mechanical ventilation mode and related settings, antimicrobial de-escalation, and central venous and urinary catheters removal. Differences in ICU and hospital length of stay, duration of mechanical ventilation, mortality rate, and hospital costs per patient were quantified between groups with patients matched for severity of illness (Simplified Acute Physiology Score II) at admission. From the 1,519 and 1,268 admitted patients during the observation and intervention periods, respectively, 1,164 patients were evaluable in both groups after matching for Simplified Acute Physiology Score II score. The intervention period was associated with mean (95% CI) reductions in patient hospital length of stay (3.7 d [5.2-2.3 d]; p < 0.001), ICU length of stay (1.4 d [2.3-0.5 d]; p < 0.005), duration of mechanical ventilation (1.2 d [2.1-0.3 d]; p < 0.01), and hospital costs per stay (2,560 euros [3,728-1,392 euros]; p < 0.001). The overall cost savings were 10,840 euros (10,727-10,952 euros) per month, mostly due to reduced consumption of sedatives and antimicrobials. No impact on mortality rate was identified. Critical care pharmacist-led interventions were associated with decreases in ICU and hospital length of stays and ICU drug costs.


Through a glass, darkly: data and uncertainty in the AIDS debate.
The HIV/AIDS epidemic is the greatest threat to development in much of Africa. It is already the main cause of death in many countries, especially those in Southern Africa. However there is an absence of solid data on the scale and scope of the disease and how it is evolving. In this article we discuss the data on the epidemic--where it comes from and how it is presented. We note the limitations of the use of antenatal clinic surveys--which provide the bulk of our information. We then turn to the evidence of impact. The paper shows that the long incubation period between infection and illness means that it takes time for HIV infections to turn into AIDS cases, and AIDS cases to translate into deaths with all the consequences of orphaning, poverty and changing population structures. Furthermore it means that once the HIV prevalence has peaked, AIDS impact will take years to work through--this epidemic is a 'long-wave' event. The paper is premised on the view that HIV causes AIDS and AIDS causes death. It notes that insufficient and/or unreliable data have allowed leaderships to deny the scope and scale of the problem and that this is unacceptable. However it is incumbent on all to accept the moral responsibility for and the moral consequences of their work, and this includes those who gather, interpret and use the data.


Terahertz emission from electric field singularities in biased semiconductors.
We use electric field singularities in biased metal semiconductor microstructures to enhance the generation of terahertz (THz) radiation from semiconductors. We find that, regardless of the mechanism that is responsible for enhanced THz emission near the anode, singular electric fields near sharp anode features will enhance this emission by as much as an order of magnitude. We show scanning THz measurements of several of these structures and discuss the physical mechanism responsible for this enhanced emission. A new family of more efficient terahertz emitters based on these effects can be designed that will improve the dynamic range of THz imaging and spectroscopy systems.


Effect of incision and flap reflection on postoperative pain after the removal of partially impacted mandibular third molars.
A clinical trial was carried out to evaluate the influence of incision and reflection of a flap on pain after the removal of partially erupted mandibular third molars. A sequential design for intraindividual comparisons was chosen. The patients underwent bilateral extraction of partially impacted mandibular third molars with a standard incision on one side (control) and without incision (test) on the other side. One week postoperatively, the patients were asked on which side they had experienced more postoperative pain. The preset level of significance (P < .05) was reached after 11 patients were treated. Eight patients had more severe pain on the control side, while three patients did not experience any difference in pain between the two sides. The nonsurgical approach did not increase the chair time and appeared to be an effective way of reducing postoperative discomfort after extraction of partially erupted third molars.


Reversible effects of green and orange-red radiation on plant cell elongation.
The differential cell elongation of cress (Lepidium sativum) roots that results in geotropic bending can be decreased by green radiation with an action spectrum peaking at 550 nm. This decrease can be negated by prior or simultaneous irradiation by orange-red light with an action spectrum peaking at 620 nm. The green radiation appears to be effective during the cell elongation phase of geotropic response.


A Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group QT/QTc Study to Evaluate the Electrophysiologic Effects of THC/CBD Spray.
Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray has proved efficacious in the treatment of spasticity in multiple sclerosis and chronic pain. A thorough QT/QTc study was performed to investigate the effects of THC/CBD spray on electrocardiogram (ECG) parameters in compliance with regulatory requirements, evaluating the effect of a recommended daily dose (8 sprays/day) and supratherapeutic doses (24 or 36 sprays/day) of THC/CBD spray on the QT/QTc interval in 258 healthy volunteers. The safety, tolerability, and pharmacokinetic profile of THC/CBD spray were also evaluated. Therapeutic and supratherapeutic doses of THC/CBD spray had no effect on cardiac repolarization with primary and secondary endpoints of QTcI and QTcF/QTcB, respectively, showing similar results. There was no indication of any effect on heart rate, atrioventricular conduction, or cardiac depolarization and no new clinically relevant morphological changes were observed. Overall, 19 subjects (25.0%) in the supratherapeutic (24/36 daily sprays of THC/CBD spray) dose group and one (1.6%) in the moxifloxacin group withdrew early due to intolerable AEs. Four psychiatric serious adverse events (AEs) in the highest dose group resulted in a reduction in the surpatherapeutic dose to 24 sprays/day. In conclusion, THC/CBD spray does not significantly affect ECG parameters. Additionally, THC/CBD spray is well tolerated at therapeutic doses with an AE profile similar to previous clinical studies.


Plasminogen-stimulated airway smooth muscle cell proliferation is mediated by urokinase and annexin A2, involving plasmin-activated cell signalling.
The conversion of plasminogen into plasmin by interstitial urokinase plasminogen activator (uPA) is potentially important in asthma pathophysiology. In this study, the effect of uPA-mediated plasminogen activation on airway smooth muscle (ASM) cell proliferation was investigated. Human ASM cells were incubated with plasminogen (0.5-50 μg·mL(-1) ) or plasmin (0.5-50 mU·mL(-1) ) in the presence of pharmacological inhibitors, including UK122, an inhibitor of uPA. Proliferation was assessed by increases in cell number or MTT reduction after 48 h incubation with plasmin(ogen), and by earlier increases in [(3) H]-thymidine incorporation and cyclin D1 expression. Plasminogen (5 μg·mL(-1) )-stimulated increases in cell proliferation were attenuated by UK122 (10 μM) or by transfection with uPA gene-specific siRNA. Exogenous plasmin (5 mU·mL(-1) ) also stimulated increases in cell proliferation. Inhibition of plasmin-stimulated ERK1/2 or PI3K/Akt signalling attenuated plasmin-stimulated increases in ASM proliferation. Furthermore, pharmacological inhibition of cell signalling mediated by the EGF receptor, a receptor trans-activated by plasmin, also reduced plasmin(ogen)-stimulated cell proliferation. Knock down of annexin A2, which has dual roles in both plasminogen activation and plasmin-signal transduction, also attenuated ASM cell proliferation following incubation with either plasminogen or plasmin. Plasminogen stimulates ASM cell proliferation in a manner mediated by uPA and involving multiple signalling pathways downstream of plasmin. Targeting mediators of plasminogen-evoked ASM responses, such as uPA or annexin A2, may be useful in the treatment of asthma.


Accuracy of screening mammography interpretation by characteristics of radiologists.
Radiologists differ in their ability to interpret screening mammograms accurately. We investigated the relationship of radiologist characteristics to actual performance from 1996 to 2001. Screening mammograms (n = 469,512) interpreted by 124 radiologists were linked to cancer outcome data. The radiologists completed a survey that included questions on demographics, malpractice concerns, years of experience interpreting mammograms, and the number of mammograms read annually. We used receiver operating characteristics (ROC) analysis to analyze variables associated with sensitivity, specificity, and the combination of the two, adjusting for patient variables that affect performance. All P values are two-sided. Within 1 year of the mammogram, 2402 breast cancers were identified. Relative to low annual interpretive volume (< or =1000 mammograms), greater interpretive volume was associated with higher sensitivity (P = .001; odds ratio [OR] for moderate volume [1001-2000] = 1.68, 95% CI = 1.18 to 2.39; OR for high volume [>2000] = 1.89, 95% CI = 1.36 to 2.63). Specificity decreased with volume (OR for 1001-2000 = 0.65, 95% CI = 0.52 to 0.83; OR for more than 2000 = 0.76, 95% CI = 0.60 to 0.96), compared with 1000 or less (P = .002). Greater number of years of experience interpreting mammograms was associated with lower sensitivity (P = .001), but higher specificity (P = .003). ROC analysis using the ordinal BI-RADS interpretation showed an association between accuracy and both previous mammographic history (P = .012) and breast density (P<.001). No association was observed between accuracy and years interpreting mammograms (P = .34) or mammography volume (P = .94), after adjusting for variables that affect the threshold for calling a mammogram positive. We found no evidence that greater volume or experience at interpreting mammograms is associated with better performance. However, they may affect sensitivity and specificity, possibly by determining the threshold for calling a mammogram positive. Increasing volume requirements is unlikely to improve overall mammography performance.


Community engagement and mobilisation of local resources to support integrated Community Case Management of childhood illnesses in Niger State, Nigeria.
Despite strong evidence of integrated community case management (iCCM) of childhood illnesses being a proven intervention for reducing childhood morbidity and mortality, sustainability remains a challenge in most settings. Community ownership and contribution are important factors in sustainability. The purpose of this study was to document the process and scale achieved for community engagement and mobilisation to foster ownership, service uptake and sustainability of iCCM activities. A review of data collected by the RAcE project was conducted to describe the scale and achievement of leveraging community resources to support the community-oriented resource persons (CORPs). The Rapid Access Expansion (RAcE)-supported iCCM programme in Niger state (2014-2017), aimed at improving coverage of case management services for malaria, pneumonia, and diarrhoea, among children aged 2-59 months. Resources donated were documented and costed based on the market value of goods and services at the time of donation. These monetary valuations were validated at community dialogue meetings. Descriptive statistics were used to summarise quantitative variables. The mean of the number of CORPs in active service and the percentages of the mobilised resources received by CORPs were calculated. The community engagement activities included 143 engagement and advocacy visits, and meetings, 300 community dialogues, reactivation of 60 ward development committees, and 3000 radio messages in support of iCCM. 79.5% of 1659 trained CORPs were still in active iCCM service at the end of the project. We estimated the costs of all support provided by the community to CORPs in cash and kind as US$ 123 062. Types of support included cash; building materials; farming support; fuel for motorcycles, and transport fares. The achievements of community engagement, mobilisation, and the resources leveraged, demonstrated acceptability of the project to the beneficiaries and their willingness to contribute to uninterrupted service provision by CORPs.


Flow-covariate prediction of stream pesticide concentrations.
Potential peak functions (e.g., maximum rolling averages over a given duration) of annual pesticide concentrations in the aquatic environment are important exposure parameters (or target quantities) for ecological risk assessments. These target quantities require accurate concentration estimates on nonsampled days in a monitoring program. We examined stream flow as a covariate via universal kriging to improve predictions of maximum m-day (m = 1, 7, 14, 30, 60) rolling averages and the 95th percentiles of atrazine concentration in streams where data were collected every 7 or 14 d. The universal kriging predictions were evaluated against the target quantities calculated directly from the daily (or near daily) measured atrazine concentration at 32 sites (89 site-yr) as part of the Atrazine Ecological Monitoring Program in the US corn belt region (2008-2013) and 4 sites (62 site-yr) in Ohio by the National Center for Water Quality Research (1993-2008). Because stream flow data are strongly skewed to the right, 3 transformations of the flow covariate were considered: log transformation, short-term flow anomaly, and normalized Box-Cox transformation. The normalized Box-Cox transformation resulted in predictions of the target quantities that were comparable to those obtained from log-linear interpolation (i.e., linear interpolation on the log scale) for 7-d sampling. However, the predictions appeared to be negatively affected by variability in regression coefficient estimates across different sample realizations of the concentration time series. Therefore, revised models incorporating seasonal covariates and partially or fully constrained regression parameters were investigated, and they were found to provide much improved predictions in comparison with those from log-linear interpolation for all rolling average measures. Environ Toxicol Chem 2018;37:260-273. © 2017 SETAC.


Enhanced pyroelectric and piezoelectric properties of PZT with aligned porosity for energy harvesting applications.
This paper demonstrates the significant benefits of exploiting highly aligned porosity in piezoelectric and pyroelectric materials for improved energy harvesting performance. Porous lead zirconate (PZT) ceramics with aligned pore channels and varying fractions of porosity were manufactured in a water-based suspension using freeze-casting. The aligned porous PZT ceramics were characterized in detail for both piezoelectric and pyroelectric properties and their energy harvesting performance figures of merit were assessed parallel and perpendicular to the freezing direction. As a result of the introduction of porosity into the ceramic microstructure, high piezoelectric and pyroelectric harvesting figures of merits were achieved for porous freeze-cast PZT compared to dense PZT due to the reduced permittivity and volume specific heat capacity. Experimental results were compared to parallel and series analytical models with good agreement and the PZT with porosity aligned parallel to the freezing direction exhibited the highest piezoelectric and pyroelectric harvesting response; this was a result of the enhanced interconnectivity of the ferroelectric material along the poling direction and reduced fraction of unpoled material that leads to a higher polarization. A complete thermal energy harvesting system, composed of a parallel-aligned PZT harvester element and an AC/DC converter, was successfully demonstrated by charging a storage capacitor. The maximum energy density generated by the 60 vol% porous parallel-connected PZT when subjected to thermal oscillations was 1653 μJ cm-3, which was 374% higher than that of the dense PZT with an energy density of 446 μJ cm-3. The results are beneficial for the design and manufacture of high performance porous pyroelectric and piezoelectric materials in devices for energy harvesting and sensor applications.


Is the 15∆ Base in Prism Test Reliable for Detection of Amblyopia in Anisometropic Patients?
The 15∆ base in prism test (15∆BIPT) introduced by Gobin is often used in The Netherlands to detect fixation preference, especially in young and preverbal children in whom a reliable measurement of the visual acuity (VA) is difficult. It is assumed that the fixation preference detected by the 15∆BIPT can be used to predict the presence of amblyopia. The aim of this retrospective case note review was to investigate the accuracy of the 15∆BIPT in detection of amblyopia in anisometropic patients. Four hundred and twelve files of anisometropic patients visiting the orthoptic department of The Rotterdam Eye Hospital were analyzed. Amblyopia was defined as an intraocular difference in VA of 2 or more Snellen lines. The sensitivity, specificity, and positive and negative predictive values of the 15∆BIPT were calculated and the receiver operating characteristic (ROC) curve was plotted. One hundred and fifty-two patients ranging from 3.3-13.1 years of age (median 5.4 years) met the inclusion criteria. One hundred and two patients were diagnosed with amblyopia. Best-corrected median VA of the best eye was 1.0 (range 0.5-1.2) and the worst eye 0.70 (range 0.05-1.2). Sensitivity of the 15∆BIPT (based on detecting amblyopia) was 34.3%. Specificity was 88.0%. The positive predictive value was 85.4% versus a negative predictive value of 39.6%. The area under the ROC curve (AUC) was 0.65 (95% CI 0.56-0.74). The low sensitivity, large number of false negatives and the AUC show that the 15∆BIPT can be considered a poor test for detecting amblyopia in anisometropic patients.


Long-term effects of an internet-based treatment for posttraumatic stress.
Advances in communication technology offer additional strategies for providing psychological treatment. Previous trials of Internet-based treatment approaches reported significant reductions in posttraumatic stress and related symptoms in response to Internet-based treatments relative to control groups. However, empirical data on the long-term effects of those approaches are sparse. In order to evaluate the long-term effect of an Internet-based intervention, the authors conducted an 18-month follow-up of an Internet-based cognitive behavioural therapy for posttraumatic stress. Severity of posttraumatic stress symptoms was the primary outcome. Additional measures were depression, anxiety, mental and physical health, and health care utilization during the follow-up period. Treatment group participants (n = 34) were assessed 1.5 years after completing treatment. Results indicated that reductions in symptoms of posttraumatic stress symptoms, depression, and anxiety found at posttreatment were sustained during the 18-month follow-up period. Preliminary evidence on long-term effects of Internet-based health care as shown in this study is promising. However, research with larger and clinically more diverse samples is needed to fully assess the clinical impact and potential of Internet-based health care provision.


Stress, immunity, cytokines and depression.
The current issue of Acta Neuropsychiatrica presents a series of papers which together provide a broad overview relating stress, immunity, cytokine activity and depressive illness, as well as the influence of cytokines on other neurological disorders. This introduction to the issue presents a broad perspective of the impact of stressors on immune functioning in animal studies and in humans, considering the potential effects of acute, subchronic and chronic stressors, as well as the contribution of previous stressor experience in promoting neurochemical and immunological alterations. Given the supposition that cytokines may act as immunotransmitters, and immune challenge may be viewed as a stressor, a brief review is provided concerning the impact of stressors and cytokine challenges on central neurochemical functioning, with particular emphasis on the commonalties between the effects of these treatments. It is suggested that by virtue of the neurochemical changes imparted by cytokines, a depressive affect may be instigated, just as it is in response to psychogenic stressors. To this end, an overview is presented concerning the relationship between cytokines and depression, as well as the influence of cytokine treatments on behavioral changes in animal studies and among patients receiving immunotherapy. Provisionally, the data support the view that activation of the inflammatory response system may contribute to affective illness, and that cytokines may act as signaling molecules to activate central nervous system processes regulating mood states.


Extinction of experimental Triatoma infestans populations following continuous exposure to dogs wearing deltamethrin-treated collars.
Dogs are domestic reservoir hosts of Trypanosoma cruzi, the etiological agent of Chagas disease. We evaluated the effect of deltamethrin-treated dog collars (DTDCs) over time on the population dynamics of Triatoma infestans, a main T. cruzi vector. Forty founder bugs of mixed life stages were allowed to colonize mud-thatched experimental huts and exposed continuously to either uncollared control dogs (N = 3) or dogs wearing DTDCs (N = 7) for a period of up to 196 days. When compared with bugs exposed to control dogs, bugs exposed to collared dogs were shown to have reduced feeding success (odds ratio [OR] = 0.40; 95% confidence interval [CI], 0.26-0.63; P < 0.001) and lower survival (OR = 0.15; 95% CI, 0.08-0.29; P < 0.001); in fact, all of the bug populations exposed to collared dogs became extinct 77-196 days after study initiation. Bugs exposed to DTDC-wearing dogs were also shown to have a lower fecundity (i.e., number of eggs produced per live female bug: OR = 0.64; 95% CI, 0.51-0.81; P < 0.001) and molting rate to first-instar nymphs (OR = 0.32; 95% CI, 0.13-0.75; P < 0.01) than those bugs exposed to control dogs. DTDCs could represent a novel tool to prevent and control canine and (hence) human Chagas disease.


Holographic data storage in a DX-center material.
We report on the optical storage of digital data in a semiconductor sample containing DX centers. The diffraction efficiency and the bit-error-rate performance of multiplexed data images are shown to agree well with a simple model of the material. Uniform storage without an exposure schedule is demonstrated. The volume sensitivity is found to be ~10(3) times that of LiNBO(3):Fe. The importance of coherent addition of scattered light with diffracted light in holographic data storage is discussed.


Elucidation of the Covalent and Tertiary Structures of Biologically Active Ts3 Toxin.
Ts3 is an alpha scorpion toxin from the venom of the Brazilian scorpion Tityus serrulatus. Ts3 binds to the domain IV voltage sensor of voltage-gated sodium channels (Nav ) and slows down their fast inactivation. The covalent structure of the Ts3 toxin is uncertain, and the structure of the folded protein molecule is unknown. Herein, we report the total chemical synthesis of four candidate Ts3 toxin protein molecules and the results of structure-activity studies that enabled us to establish the covalent structure of biologically active Ts3 toxin. We also report the synthesis of the mirror image form of the Ts3 protein molecule, and the use of racemic protein crystallography to determine the folded (tertiary) structure of biologically active Ts3 toxin by X-ray diffraction.


A treacherous case of primary non-Hodgkin lymphoma of the bone: appearances can be deceptive.
Primary lymphoma of the bone constitutes an extremely rare but distinctive clinical entity, accounting for approximately 3% of all primary bone malignancies and less than 1% of all non-Hodgkin lymphomas. We report a rare case of a male patient with an atypical clinical presentation of non-Hodgkin primary lymphoma of the bone, initially misdiagnosed as ankylosing spondylitis. To our knowledge, this is the first case in the literature in which magnetic resonance imaging was contra-indicated. The atypical radiological imaging of the tumor, despite its aggressiveness, rendered the diagnostic approach a challenging but strenuous process. Plain radiographs and even computerized tomography images of primary lymphoma of the bone may appear as normal, but other imaging modalities should be used including radionuclide scans, especially when imaging techniques of greater accuracy such as magnetic resonance imaging are contraindicated. A patient-centred approach with emphasis on the main symptoms is the key to the diagnostic challenge of revealing the extremely unusual cases of primary lymphoma of the bone.


Virtual Reality for the Treatment of Anxiety Disorders: A Scoping Review.
Virtual reality in head-mounted displays (HMD-VR) may be a valuable tool in occupational therapy to address anxiety. Findings from the virtual reality exposure therapy (VRET) literature may facilitate translation of HMD-VR to occupational therapy psychosocial practice. To explore how HMD-VR has been used to treat anxiety through VRET and could be translated to occupational therapy. We searched seven electronic databases for articles published between 2000 and 2020: CINAHL, Cochrane Library, Embase, ERIC, Ovid MEDLINE, PsycINFO, and Web of Science. Search terms included HMD-VR constructs, products, and therapy concepts. Study Selection and Data Collection: We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to report studies implementing VRET to treat anxiety. At least two reviewers assessed each citation, and a third resolved disagreements. Articles were included if they were in English, reported experimental data, and used HMD-VR. Letters, commentaries, book chapters, technical descriptions, theoretical papers, conference proceedings (≤4 pages), and reviews were excluded. Twenty-eight studies used HMD-VR to treat posttraumatic stress disorder (n = 3), specific phobias (n = 19), and performance-based social anxiety (n = 6); protocols and levels of evidence varied (randomized controlled trials, n = 11; controlled trials without randomization, n = 6; case-control or cohort studies, n = 11). Qualitative examination indicates HMD-VR is an effective treatment tool. HMD-VR can be a valuable tool for occupational therapy to simulate environments where clients with anxiety disorders participate. Eliciting presence through multisensory features and body representation may enhance outcomes. What This Article Adds: Drawing from the VRET literature, this scoping review suggests that HMD-VR can be used by occupational therapy practitioners to simulate ecologically valid environments, evaluate client responses to fearful stimuli, and remediate anxiety though immersion in virtual tasks when participation in natural contexts is unfeasible. Having ecologically valid environments is particularly important for people with anxiety disorders because they need support to cope when they encounter triggers in everyday life environments.


Binding of DC-HIL to dermatophytic fungi induces tyrosine phosphorylation and potentiates antigen presenting cell function.
APCs express receptors recognizing microbes and regulating immune responses by binding to corresponding ligands on immune cells. Having discovered a novel inhibitory pathway triggered by ligation of DC-HIL on APC to a heparin/heparan sulfate-like saccharide of syndecan-4 on activated T cells, we posited DC-HIL can recognize microbial pathogens in a similar manner. We showed soluble recombinant DC-HIL to bind the dermatophytes Trichophyton rubrum and Microsporum audouinii, but not several bacteria nor Candida albicans. Dermatophyte binding was inhibited completely by the addition of heparin. Because DC-HIL contains an ITAM-like intracellular sequence, we questioned whether its binding to dermatophytes can induce tyrosine phosphorylation in dendritic cells (DC). Culturing DC with T. rubrum (but not with C. albicans pseudohyphae) induced phosphorylation of DC-HIL, but not when the tyrosine residue of the ITAM-like sequence was mutated to phenylalanine. To examine the functional significance of such signaling on DC, we cross-linked DC-HIL with mAb (surrogate ligand), which not only induced tyrosine phosphorylation but also up-regulated expression of 23 genes among 662 genes analyzed by gene-array, including genes for profilin-1, myristoylated alanine rich protein kinase C substrate like-1, C/EBP, LOX-1, IL-1beta, and TNF-alpha. This cross-linking also up-regulated expression of the activation markers CD80/CD86 and heightened APC capacity of DC to activate syngeneic T cells. Our findings support a dual role for DC-HIL: inhibition of adaptive immunity following ligation of syndecan-4 on activated T cells and induction of innate immunity against dermatophytic fungi.


Rural Women's Experience of Living and Giving Birth in Relief Camps in Pakistan.
Women are more vulnerable than men in the same natural disaster setting. Preexisting gender inequality, socio-cultural community dynamics and poverty puts women at significant risk of mortality. Pregnant women are particularly vulnerable because of their limited or no access to prenatal and obstetric care during any disaster or humanitarian emergency setting. In-depth interviews were conducted with 15 women who gave birth during the 2011 floods in Sindh Province, Pakistan. Thematic analysis explored women's experiences of pregnancy and giving birth in natural disaster settings, the challenges they faced at this time and strategies they employed to cope with them. Results: Women were not afforded any control over decisions about their health and safety during the floods. Decisions about the family's relocation prior to and during the floods were made by male kin and women made no contribution to that decision making process. There were no skilled birth attendants, ambulances, birthing or breastfeeding stations and postnatal care for women in the relief camps. Women sought the assistance of the traditional birth attendants when they gave birth in unhygienic conditions in the camps. The absence of skilled birth attendants and a clean physical space for childbirth put women and their newborn infants at risk of mortality. A clean physical space or birthing station with essential obstetric supplies managed by skilled birth attendants or community health workers can significantly reduce the risks of maternal morbidity and mortality in crisis situations.