Expression of asparagine synthetase in rice (Oryza sativa) roots in response to nitrogen.
The expression of asparagine synthetase (AS; EC 126.96.36.199) in response to externally supplied nitrogen was investigated with respect to enzyme activity and protein levels as detected immunologically in rice (Oryza sativa) seedlings. The asparagine content was very low in leaves and roots of nitrogen-starved rice plants but increased significantly after the supply of 1 mM NH4+ to the nutrient solution. While neither AS activity nor AS protein could be detected in leaves and roots prior to the supply of nitrogen, levels became detectable in roots but not in leaves within 12 h of the supply of 1 mM NH4+ or 10 mM glutamine. Other nitrogen compounds, such as nitrate, glutamate, aspartate and asparagine had no effect. Methionine sulfoximine completely inhibited the NH4+-induced accumulation of AS protein but did not affect the glutamine-induced accumulation of the enzyme. The results suggested that glutamine or glutamine-derived metabolites regulate AS expression in rice roots.


Beetles (Coleoptera) in deciduous dead wood tree species trunks in Lithuania.
We present a list of beetles that emerged from wind-felled tree trunks of several tree species, including European ash (Fraxinusexcelsior), aspen (Populustremula), common oak (Quercusrobur), birch (Betula sp.), small-leaved linden (Tiliacordata) and black alder (Alnusglutinosa). Four hundred and ninety species and 60 families of beetles were collected using trunk-emergence type traps. We found 440 beetle species that had previously been recorded from dead wood; the remaining 50 were newly discovered and all were considered as not directly associated with dead wood. Common oak trunks had the highest diversity of beetles, with approximately 42% of the identified beetle species found in our research. Of all the beetle species identified in the study, about half are saproxylic, while the remaining are considered as not having direct association with dead wood. The results of the study emphasise the importance of dead wood in maintaining beetle diversity in Lithuanian forests. This study provides a valuable baseline for future research on beetles in dead wood in Lithuania and may help to provide information for conservation efforts to protect these important habitats.


Wound coverage technologies in burn care: novel techniques.
Improvements in burn wound care have vastly decreased morbidity and mortality in severely burned patients. Development of new therapeutic approaches to increase wound repair has the potential to reduce infection, graft rejection, and hypertrophic scarring. The incorporation of tissue-engineering techniques, along with the use of exogenous proteins, genes, or stem cells to enhance wound healing, heralds new treatment regimens based on the modification of already existing biological activity. Refinements to surgical techniques have enabled the creation of protocols for full facial transplantation. With new technologies and advances such as these, care of the severely burned will undergo massive changes over the next decade. This review centers on new developments that have recently shown great promise in the investigational arena.


TRAIL, Wnt, Sonic Hedgehog, TGFβ, and miRNA Signalings Are Potential Targets for Oral Cancer Therapy.
Clinical studies and cancer cell models emphasize the importance of targeting therapies for oral cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is highly expressed in cancer, and is a selective killing ligand for oral cancer. Signaling proteins in the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt), Sonic hedgehog (SHH), and transforming growth factor β (TGFβ) pathways may regulate cell proliferation, migration, and apoptosis. Accordingly, the genes encoding these signaling proteins are potential targets for oral cancer therapy. In this review, we focus on recent advances in targeting therapies for oral cancer and discuss the gene targets within TRAIL, Wnt, SHH, and TGFβ signaling for oral cancer therapies. Oncogenic microRNAs (miRNAs) and tumor suppressor miRNAs targeting the genes encoding these signaling proteins are summarized, and the interactions between Wnt, SHH, TGFβ, and miRNAs are interpreted. With suitable combination treatments, synergistic effects are expected to improve targeting therapies for oral cancer.


A Bayesian approach for the separation of the acoustic and the correlated aerodynamic wall pressure fluctuations.
When performing measurements with wall-installed microphone array, the turbulent boundary layer that develops over the measuring system can induce pressure fluctuations that are much greater than those of acoustic sources. It then becomes necessary to process the data to extract each component of the measured field. For this purpose, it is proposed in this paper to decompose the measured spectral matrix into the sum of matrices associated with the acoustic and aerodynamic contributions. This decomposition exploits the statistical properties of each pressure field. On the one hand, assuming that the acoustic contribution is highly correlated over the sensors, the rank of the corresponding cross-spectral matrix is limited to a finite number. On the other hand, the correlation structure of the aerodynamic noise matrix is constrained to resemble a Corcos-like model, with physical parameters estimated within the separation procedure. This separation problem is solved by a Bayesian inference approach, which takes into account the uncertainties on each component of the model. The performance of the method is first evaluated on wind tunnel measurements and then on a particularly noisy industrial measurement setup: microphones flush-mounted on the fuselage of a large aircraft.


Comparative Evaluation of Ropivacaine and Ropivacaine with Dexamethasone in Transverse Abdominis Plane Block for Lower Abdominal Surgeries: A Prospective, Randomized, Double-Blinded Study.
Dexamethasone as an adjunct to ropivacaine has shown promising results in prolonging the duration of analgesia in transverse abdominis plane (TAP) block. Only limited studies evaluated the effects of dexamethasone with ropivacaine in TAP block in specific population. The effects of adding dexamethasone to ropivacaine on the quality and duration of TAP block in lower abdominal surgeries in multiple specialties were studied. This was a prospective, randomized, double-blinded study. Seventy adult patients undergoing lower abdominal surgeries were allocated into two groups to receive general anesthesia with TAP block with 20 ml 0.25% ropivacaine with 8 mg dexamethasone (2 ml) (Group A, n = 35) or 20 mL 0.25% ropivacaine with 2 ml saline (Group B, n = 35) each side. The analgesic efficacy in terms of pain scores, morphine consumption, and occurrence of nausea and vomiting was compared between two groups. Data were analyzed with SPSS 23 with independent t-test and Chi-square test as applicable. P < 0.05 was considered statistically significant. The duration of analgesia was significantly prolonged in Group A (P = 0.000). The total morphine consumption was significantly lesser in Group A (P = 0.000). The pain scores (numerical pain intensity scale) were significantly lesser in Group A till the 8th postoperative hours. The occurrence of nausea and vomiting was comparable between the groups (P = 0.3821). Addition of dexamethasone to ropivacaine significantly improved the quality of analgesia with reduced consumption of opioids as compared to plain ropivacaine in TAP block.


Influence of nutritional iron deficiency anemia on DNA stability and lipid peroxidation in rats.
Oxidative stress results from an imbalance between the formation and neutralization of pro-oxidants. Disturbance of the pro-oxidant/antioxidant balance is also considered to be a causative factor underlying oxidative damage to cellular molecules, such as DNA, causing strand breaks. There is considerable controversy about the antioxidant status in iron-deficiency anemia (IDA), but scant information is available regarding DNA integrity. In the present study, we investigated the relation between DNA stability and hepatic antioxidant capacity in rats with induced IDA. Peripheral DNA damage was assessed using an alkaline comet assay. Further, the hepatic antioxidant enzyme glutathione peroxidase and the production of thiobarbituric acid-reactive substances were measured in control rats and in those with induced IDA. Comparison of the control and anemic rats showed no differences in thiobarbituric acid-reactive substances production in the cytosolic fraction of hepatic cells. Nor were there any differences in liver glutathione peroxidase enzyme activity or DNA stability, as demonstrated by the percentage of DNA in the head (90.77 in control rats versus 88.23 in anemic rats), tail (9.23 in control rats versus 11.76 in anemic rats), and olive tail moment (0.155 in control rats versus 0.141 in anemic rats). IDA does not affect DNA stability or lipid peroxidation in rats, suggesting that there is enough compensatory capacity to keep antioxidant defenses high.


[Duration of action of the pyrimethamine-sulfametopyrazine combination in a Plasmodium falciparum endemic zone].
The duration of action of the drug Antemal, a combination of Pyrimethamine and Sulfametopyrazine, was eveluated in Bobo-Dioulasso, Upper Volta, West Africa, and endemic zone for Plasmodium falciparum malaria. The study was held during the season of maximum malaria transmission. 79 persons presenting with an acute attack of malaria were studied; 37 persons received a single dose of chloroquine sulfate (Nivaquine), at a dose of 15 mg./kg.; 42 persons received a single dose of Antemal at a dose of one tablet (75 mg. of Pyrimethamine and 25 mg. of Sulfametopyrazine) per 10 kg. Clinical and parasitological studies of all subjects occurred on days one, two, three, 10, 17, 24 and 31. Only one of 37 (2.7%) subjects on Antemal had a reappearance of trophozoites, occurring on day 17. Eight of 42 (19.0%) patients taking nivaquine had reappearance of trophozoites, observed between day 23 and 31. Gametocytes were observed in eight of 37 (21.6 %) persons on Antemal and in only one of 42 (2.3 %) persons on Nivaquine. These observations suggest an extended duration of protection from Antemal in semi-immune individuals. Nivaquine appeared as a potent inhibitor of gametocytogenesis.


Women's migration to cities.
This study investigates the consequences of female rural-urban migration with respect to their education, career, and relationship and family formation in the Netherlands. The study is based on four birth cohorts of Dutch women born in 1970-1973 in rural areas, comparing those who had migrated to urban areas before the age of 25 with those who had remained behind. Outcomes were measured at age 42. The data were derived from administrative registers available at Statistics Netherlands. The results show that female migration to cities served to increase women's resources: they were more often university educated and had better paid jobs, in line with the idea of cities as socioeconomic escalators. The city also functioned as a relationship market with a relative abundance of men with resources. Both lower and university educated city women were more likely to be in a relationship with a highly educated man compared to their rural peers. However, lower educated women had an increased probability of being single at age 42 when they lived in cities at age 25. This was not the case for university educated women. In conclusion, for lower educated women urban migration may entail risks as well as benefits, especially with respect to family formation. University educated women on the other hand benefited both in terms of their own socioeconomic outcomes and in terms of their partners' resources.


Advances in biomarkers for paediatric rheumatic diseases.
The search for biomarkers in paediatric rheumatic diseases, particularly juvenile idiopathic arthritis (JIA), childhood lupus nephritis (LN), and juvenile idiopathic inflammatory myopathies (JIIMs) is attracting increased interest. In JIA, a number of biomarkers have shown potential for predicting clinical phenotype, disease activity and severity, clinical remission and relapse, response to treatment, and disease course over time. In systemic JIA, measurement of biomarkers that reflect the degree of activation and expansion of T cells and macrophages might be helpful for detecting subclinical macrophage activation syndrome. Urine biomarkers for childhood LN hold promise for facilitating early diagnosis and improving disease monitoring and assessment of response to therapy. Myositis-specific autoantibodies define distinct serological subgroups of JIIMs, albeit with similar clinical features, responses to therapy, and prognoses. Use of biomarkers may potentially help to avoid invasive procedures, such as renal biopsy in systemic lupus erythematosus and muscle biopsy in juvenile dermatomyositis. Incorporation of effective and reliable biomarkers into routine practice might facilitate adoption of a stratified approach to investigation and management, foster the implementation of research into the design of personalized and targeted therapies, and ultimately lead to more rational and effective clinical care.


Protective behavior and West Nile virus risk.
We conducted a cross-sectional, household survey in Oakville, Ontario, where an outbreak of West Nile virus (WNV) in 2002 led to an unprecedented number of cases of meningitis and encephalitis. Practicing > or =2 personal protective behavior traits reduced the risk for WNV infection by half.


Pathogenic Role of IL-17-Producing Immune Cells in Obesity, and Related Inflammatory Diseases.
Obesity is associated with low-grade chronic inflammation. Indeed, adipose tissues (AT) in obese individuals are the former site of progressive infiltration by pro-inflammatory immune cells, which together with increased inflammatory adipokine secretion induce adipocyte insulin resistance. IL-17-producing T (Th17) cells are part of obese AT infiltrating cells, and are likely to be promoted by adipose tissue-derived mesenchymal stem cells, as previously reported by our team. Whereas Th17 cell are physiologically implicated in the neutralization of fungal and bacterial pathogens through activation of neutrophils, they may also play a pivotal role in the onset and/or progression of chronic inflammatory diseases, or cancer, in which obesity is recognized as a risk factor. In this review, we will highlight the pathogenic role of IL-17A producing cells in the mechanisms leading to inflammation in obesity and to progression of obesity-related inflammatory diseases.


Dietary influence on the insulin function in the epididymal fat cell of the Wistar rat. III. Effect of the ratio carbohydrate to fat.
Newly weaned male Wistar rats were fed semipurified diets containing sunflowerseed oil or palm oil. The fatty acid compositions of the phospholipid and triacylglycerol fractions either from whole epididymal fat pads or from fat cells isolated from the pads appeared to be nearly similar. Feeding the diets for a period of only 3-4 weeks after weaning was found to be sufficient to produce a difference in insulin response and insulin binding in the epididymal fat cells. A reduction in the dietary fat content from 30 to 15% of the energy had only minor effects on fat pad weight and on the fatty acid composition of the phospholipid- and triacylglycerol fractions isolated from the epididymal fat pads. There was no effect either on body weights or on average fat cell diameter but there was an increase in insulin response in the isolated fat cells, however. The difference in insulin response after a diet rich in polyunsaturated fatty acids (sunflowerseed oil) as compared to one rich in saturated fatty acids (palm oil) remained after the reduction of fat content.


[Polymorphism analysis of 825C/T of the G-protein beta 3 subunit in high risk population of hypertension in the northeast China].
PCR-RFLP was used for genotyping of GNB3 C/T in 133 patients with EH and 257 healthy control subjects in the high risk population and in 98 patients with EH and 110 healthy control subjects in general population. Some biochemical tests were performed also. The association between the polymorphism and blood pressure was analyzed by the case-control study. Not association between GNB3 825C/T polymorphism and blood pressure was found in both populations. CT and TT genotypes in women of the high risk population are associated with diastolic blood pressure, serum sodium and calcium. Although GNB3 is not a susceptible gene of hypertension in the northeast Chinese, it still has some effects on regulation of the blood pressure in susceptible women.


Ten Core Competencies for Hospital Administrators.
Ever-increasing complexity and contradiction in the health care industry often leave hospital administrators wondering whether they can still make a positive difference for patients. In this context, hospital administrators can regain both perspective and enthusiasm by revitalizing their direct connections with the patients, caregivers, and organizations they serve. Hospital administration remains a special calling, and this article profiles 10 core competencies that will keep health professionals close to their customers, colleagues, and the reasons they entered the helping professions. This intimate knowledge of the organization and its resources coupled with the ability to communicate effectively typically trump advanced education or technical skills in successfully navigating genuinely consequential situations. Hospital administrators who master and practice the 10 competencies can indeed make a positive difference for patients and find great personal reward in doing so.


The Impact of Mediterranean Dietary Intervention on Metabolic and Hormonal Parameters According to BRCA1/2 Variant Type.
The female carriers of BRCA1/2 pathogenic variants (mutations) face a high lifetime risk of developing breast and/or ovarian cancer. However, the risk may differ depending on various genetic and non-genetic elements, including metabolic and hormonal factors. We previously showed that a 6-month Mediterranean dietary intervention trial reduced body weight and the levels of insulin-like growth factor I and other metabolic factors in BRCA mutation carriers. We also found that higher baseline levels of glucose and insulin were significantly associated with BRCA loss-of-function (LOF) variants. In this study, we evaluated whether the BRCA mutation type influences in a different way the metabolic and hormonal response to the dietary intervention in 366 female carriers. The LOF variant carriers randomized in the intervention group (IG) showed significantly higher changes in most considered parameters compared to the control group (CG). The nonsynonymous variant carriers in the IG showed similar changes, but none of them were statistically significant. Performing the "delta" analysis of differences (intention-to-treat analysis), we observed that in LOF variant carriers, the reduction of insulin levels was significantly more pronounced that in nonsynonymous variant carriers. These findings suggest that the changes in insulin levels might be modulated by a different response to the dietary intervention mediated by BRCA LOF variants.


"Does It Really Get Better After Dad Leaves?" Children's Experiences With Domestic Violence: A Qualitative Systematic Review.
Domestic violence (DV) can persist and escalate post-separation. However, little focus has been given to children exposed to DV during this period. This review aims to consolidate the available evidence on children's post-separation experiences with DV caused by their fathers. A qualitative systematic review was carried out. Six electronic databases were searched from the inception of each database until July 2022. Qualitative studies of children aged below 24 years, with biological fathers that committed DV, of which each had experienced parental separation were selected. Twenty studies were included in this review after screening according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Using Sandelowski and Barroso's analysis method, a meta-summary and a meta-synthesis were conducted. Three major themes with eight subthemes were identified: (1) continued abuse post-separation, (2) child's wavering mind of their fathers, and (3) wrangling between past and present. Overall, the findings highlighted that the experience of DV persisted post-separation through various forms of abuse. Children also struggled with mixed feelings and thoughts toward their fathers. They found it hard to trust their fathers and were cautious about their fathers' intentions regarding love and interest. Some children had difficulty interacting with their fathers and were exploited by them. Different stakeholders such as healthcare professionals and court officials can play a significant role in supporting and protecting children exposed to DV and schools can play a significant role in empowering children against DV.


Intersectional perspectives on the employment rate in Supported Employment for people with psychiatric, neuropsychiatric, or intellectual disabilities: A scoping review.
Supported Employment (SE) has shown better results in the employment rate for persons with disabilities than other methods within vocational rehabilitation, but how SE affects the employment rate for subgroups in the interventions needs further attention. To examine previous research regarding the influence of intersecting statuses on the employment rate in SE for people with psychiatric, neuropsychiatric, or intellectual disabilities according to type of diagnosis, sex, race/ethnicity, age, level of education and previous work history. A systematic literature search was conducted in nine databases including peer-reviewed articles from 2000 to April 2021. Articles presenting the employment rate in SE interventions according to the intersecting statuses listed in the objective were included. The searches identified 3777 unique records, of which 53 articles were included in data extraction. In most of the included articles, intersecting statuses did not affect the employment rate for people in the SE interventions with psychiatric disabilities. Few studies have examined neuropsychiatric and intellectual disabilities. A majority of the studies subjected to full-text analysis were excluded due to a lack of reporting of the effects of intersecting statuses on the employment rate. The studies that reported on the effects of intersecting statuses on the employment rate often had small samples and lacked statistical power. Intersecting statuses do not appear to affect the employment rate for people receiving SE interventions, but systematic reviews with pooled samples need to be undertaken because of the low reporting rate and underpowered sample sizes in existing studies.


Pharmacokinetics and bioequivalence of two methylprednisolone tablet formulations in healthy Chinese subjects under fasting and fed conditions.
The aims of this study were to evaluate and compare the pharmacokinetic profiles and bioequivalence of two tablet formulations of methylprednisolone (test formulation: Zhejiang Xianju Pharmaceutical Co., Ltd., China; reference formulation: Medrol, Pfizer Italia SRL) in healthy Chinese subjects under fasting and fed conditions. Subjects were randomly allocated to either the fasting group or the fed group and also to one of two sequences (test-reference or reference-test), according to which they received a single 16-mg dose of the test or reference methylprednisolone tablet in the study periods. Blood samples were collected pre dose and at intervals up to 16 hours after administration. Plasma methylprednisolone concentrations were determined using a validated liquid chromatography tandem mass spectrometry method. The safety of the medications was monitored throughout the study. The primary pharmacokinetic parameters measured were Cmax, AUC0-t, and AUC0-∞. A total of 56 subjects were enrolled, and all completed the study. The 90% confidence intervals for Cmax, AUC0-t, and AUC0-∞, measured under both fasting and fed conditions, fell within the acceptable range for bioequivalence of 80 - 125%. Analysis of variance showed that there were no significant differences in the primary pharmacokinetic parameters (Cmax, AUC0-t, and AUC0-∞) between the test and reference formulation measured under both fasted and fed conditions. No serious or unexpected adverse drug reactions occurred during the study period. The test methylprednisolone 16 mg tablet produced in China is bioequivalent to the reference formulation (Medrol) in healthy Chinese subjects measured under both fasting and fed conditions. Both formulations were well tolerated by all study participants.


The effect of impairment of blood supply to the rat uterus.
Over the last decades much attention has been directed to establishing the cause of altered fetal growth and habitual abortion. Great emphasis has been placed on placental blood flow, but relatively few studies have been published on the effect of impaired uterine blood supply. This study examined the effect of impaired uterine blood flow using the white rat, with its bilateral uterine horns. Three groups of rats with bilateral, left unilateral, or right unilateral artery ligation were compared with a control group for number and weight of fetuses at term. The results showed that the impaired rats produced significantly fewer fetuses than controls (means: 8.59 vs. 11.21, respectively; P less than .001) and those fetuses had lower mean birth weights than controls (5.295 g vs. 5.800 g, respectively; P less than .05). While conception was possible even in rats with impaired uterine blood flow, the differences at term suggest that impairment of the maternal blood flow may contribute toward intrauterine growth retardation and habitual abortion. The clinical significance of these findings and suggestions for future research are discussed.


Effects of ischemic tolerance on mRNA levels of IP3R1, beta-actin, and neuron-specific enolase in hippocampal CA1 area of the gerbil brain.
Global cerebral ischemia induced to Mongolian gerbils by ligation of common carotid arteries (CCAs) is known to result in injury to the hippocampal CA1 region. In this study, we examined whether neuronal injury can be depicted by measuring levels of mRNA encoding inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), neuron specific enolase (NSE) and beta-actin and whether these measurements can be use to assess ischemic tolerance. Gerbils were subjected either to cerebral ischemia induced by ligation of both CCAs for 5 min, or to an ischemic tolerance paradigm in which a 2 min ischemic preconditioning was performed 24 hr prior to the 5 min ischemia. At 48 hr after the 5 min ischemic insult, significant decreases in mRNA levels for IP3R1 (26%), NSE (38%) and beta-actin (50%) could be observed in the hippocampal CA1 region. Although levels of mRNA in the preconditioning group were decreased as compared to the sham control, the levels were significantly higher than those in the ischemic group. These results indicate the feasibility of using mRNA measurement as a parameter to assess cerebral ischemic damage. In addition, based on the differences in the decline in mRNA levels between the ischemia group and the preconditioned ischemia group, it can be concluded that this ischemic tolerance paradigm could offer partial protection (around 45%) against the injury due to the 5 min cerebral ischemic insult.


When plausibility manipulations work: an examination of their role in the development of false beliefs and memories.
In the current study we examined whether prevalence information and imagery encoding influence participants' general plausibility, personal plausibility, belief, and memory ratings for suggested childhood events. Results showed decreases in general and personal plausibility ratings for low prevalence events when encoding instructions were not elaborate; however, instructions to repeatedly imagine suggested events elicited personal plausibility increases for low-prevalence events, evidence that elaborate imagery negated the effect of our prevalence manipulation. We found no evidence of imagination inflation or false memory construction. We discuss critical differences in researchers' manipulations of plausibility and imagery that may influence results of false memory studies in the literature. In future research investigators should focus on the specific nature of encoding instructions when examining the development of false memories.


Early-onset unilateral electric cataract: a rare clinical entity.
Electrical injury may result in cataracts, which usually occur bilaterally. In this report, we present a rare complication of such an injury presenting as a unilateral cataract in a 33-year-old woman with a painless but gradual worsening of vision in her left eye 3 weeks after sustaining a high-voltage electrical injury. A cataract did not develop in the right eye during 26 months of follow-up. The patient underwent successful cataract surgery with an excellent return of vision. Electrical injuries may result in the formation of a unilateral cataract and therefore an ophthalmic examination should be performed regularly in the early recovery period of such injuries. Cataract surgery with intraocular lens implantation results in an excellent return of vision in patients with electrical cataract who do not have any other ocular damage.


Lymphokine production by human milk lymphocytes.
To assess the functional capability of human milk lymphocytes, we studied phytohemagglutinin-induced lymphokine production by breast milk and, for comparison, peripheral blood lymphocyte cultures. Two lymphokines, lymphocyte-derived chemotactic factor (LDCF) and immune interferon, were assayed in supernatants of milk and blood lymphocyte cultures obtained from women 2 to 6 days postpartum. Eleven parallel milk and blood samples were studied for LDCF production. In nine experiments, both milk and blood lymphocytes produced LDCF. In the two other experiments, milk cells did not produce LDCF. In 10 milk cultures studied, all produced interferon activity. Acid and heat lability characteristics were typical of immune interferon. These results further characterize milk lymphocytes as immunologically competent and possibly important effector cells in neonatal immunity.


The pancreatic enzymes value in the diagnosis of acute pancreatitis and acute biliary tract diseases.
The aim of this study was to investigate the usefulness of lipase and isoamylases in the diagnosis of acute pancreatitis and to determine if its use permits differential diagnosis between acute pancreatitis and acute biliary tract disease. Three groups of patients were studied. a) 60 patients without abdominal diseases. b) Acute pancreatitis: 60 patients, the diagnosis was made according to clinical symptoms, biochemical tests, U.S. and C.T. in 24 (40%), in the remainder 36 (60%) surgical confirmation was obtained. c) Acute biliary tract disease without macroscopic pancreatic damage, 30 patients, the diagnosis was made according to biochemical tests and U.S. in 4 (13.3%) whereas in the remainder 26 (86.6%) surgical confirmation was accomplished no later than a week of the beginning of the symptoms. Biochemical tests: serum and urine amylase, lipase, and total pancreatic and salivary isoamylases were evaluated. In the group of acute pancreatitis the highest diagnostic sensibility was: pancreatic isoamylase 95.5%, lipase 95%, total serum amylase 93.3% urine amylase 90%, serum amylase 78.3%. In acute biliary tract diseases a high number of elevated enzyme values were also found: pancreatic isoamylase 83.3%, total isoamylase 73.3%, urine amylase 66.6%, lipase 63.3%, serum amylase 53.3%. The mean enzyme values of both groups were compared statistically and showed no significant difference. We conclude that lipase and isoamylases are the best markers for the diagnosis of acute pancreatitis and the differential diagnosis with acute biliary diseases is difficult because an elevation of these enzymes is a characteristic shared by both pathologies. The diagnosis of acute pancreatitis based only in clinical symptoms and hyperamylasemia can be erroneous.


An Uncommon Cause of Small Bowel Bleeding from Appendiceal Carcinoma.
Massive hematochezia caused by a small bowel lesion is a rare entity. Currently, video capsule endoscopy and balloon-assisted enteroscopy are effective in identifying the source of small intestine bleeding. Herein, we report a case of small bowel bleeding caused by a nonmucinous appendiceal adenocarcinoma with ileal invasion which was detected by video capsule endoscopy and single-balloon endoscopy. Despite the advanced disease stage with hepatic and peritoneal metastases, as of September 2016 the patient has had 8 years' disease-free survival after surgical resection and chemotherapy.


Linear Four-Chalcogen Interactions in Radical Cationic and Dicationic Dimers of 1,5-(Dichalcogena)canes: Nature of the Interactions Elucidated by QTAIM Dual Functional Analysis with QC Calculations.
The dynamic and static nature of extended hypervalent interactions of the BE···AE···AE···BE type are elucidated for four center-seven electron interactions (4c-7e) in the radical cationic dimers (1·+) and 4c-6e in the dicationic dimers (12+) of 1,5-(dichalcogena)canes (2: AE(CH2CH2CH2)2BE: AE, BE = S, Se, Te, and O). The quantum theory of atoms-in-molecules dual functional analysis (QTAIM-DFA) is applied for the analysis. Total electron energy densities Hb(rc) are plotted versus Hb(rc) - Vb(rc)/2 [= (ℏ2/8m)∇2ρb(rc)] at bond critical points (BCPs) of the interactions, where Vb(rc) values show potential energy densities at BCPs. Data from the fully optimized structures correspond to the static nature of the interactions. Those from the perturbed structures around the fully optimized ones are also plotted, in addition to those of the fully optimized ones, which represent the dynamic nature of interactions. The BE···AE-AE···BE interactions in 12+ are stronger than the corresponding ones in 1·+, respectively. On the one hand, for 12+ with AE, BE = S, Se, and Te, AE···AE are all classified by the shared shell interactions and predicted to have the weak covalent nature, except for those in 1a2+ (AE = BE = S) and 1d2+ (AE = BE = Se), which have the nature of regular closed shell (r-CS)/trigonal bipyramidal adduct formation through charge transfer (CT-TBP). On the other hand, AE···BE are predicted to have the nature of r-CS/molecular complex formation through charge transfer for 1a2+, 1b2+ (AE = Se; BE = S), and 1d2+ or r-CS/CT-TBP for 1c2+ (AE = Te; BE = S), 1e2+ (AE = Te; BE = Se), and 1f2+ (AE = BE = Te). The BE···AE-AE···BE interactions in 1·+ and 12+ are well-analyzed by applying QTAIM-DFA.


A border context of violence: Mexican female sex workers on the U.S.-Mexico border.
Female sex workers (FSW) represent a population confronted with an array of intersecting social problems. We explore the case of FSW in Nuevo Laredo and Ciudad Juarez to understand the everyday violence associated with sex work within the unique context of Mexico. Life history interviews were conducted with 109 FSW revealing violent acts by clients and other sex industry employees (bar owners, police, other FSW). The risk of violence by different types of persons associated with the sex work industry varied by venue and geographic area. Moreover, the violence was shaped by the social structural constraints of dominant gender ideologies.


A meta-analysis on the prevalence and characteristics of severe malaria in patients with Plasmodium spp. and HIV co-infection.
Co-infection with malaria and human immunodeficiency virus (HIV) increases the severity and mortality rates of both diseases. A better understanding of the effects of co-infections could help in the diagnosis, prompt treatment, prevention, and control of malarial parasites among HIV-infected patients. In this systematic review and meta-analysis, we estimated the prevalence and characteristics of severe malaria (SM) caused by co-infection with HIV. We included relevant studies that were conducted between the years 1991 and 2018 and reporting on SM. We pooled the prevalence of SM in patients with co-infection, pooled odds ratios of SM in patients with co-infection and Plasmodium mono-infection, and differences in laboratory parameters such as parasite density and leucocyte counts, between co-infected and Plasmodium mono-infected patients. The meta-analysis included 29 studies (1126 SM cases). The pooled prevalence of SM in co-infected patients using the data of 23 studies (SM = 795 cases, all co-infection cases = 2534 cases) was 43.0% (95% confidence interval [CI] 31.0-56.0%; I2, 98.0%). Overall, the odds of SM from 18 studies were pooled. The odds of SM were significantly higher in co-infected patients than in Plasmodium mono-infected patients (OR 2.41; 95% CI 1.43-4.08; I2 = 85%; P = 0.001) and also significantly higher in children (OR 9.69; 95% CI 5.14-18.3; I2, 0%; P < 0.0001; two studies) than in adults (OR 2.68; 95% CI 1.52-4.73; I2, 79.0%; P = 0.0007; 12 studies). Co-infected patients with SM had a higher parasite density than those with Plasmodium mono-infection when the data of seven studies were analysed (SMD, 1.25; 95% CI 0.14-2.36; I2, 98.0%; P = 0.03) and higher leukocyte counts when the data of four studies were analysed (MD, 1570 cells/µL; 95% CI 850-2300 cells/µL; I2, 21.0%; P < 0.0001). Thus, the prevalence of SM among patients co-infected with Plasmodium spp. and HIV is high. Because co-infections could lead to SM, patients with Plasmodium spp. and HIV co-infection should be identified and treated to reduce the prevalence of SM and the number of deaths.


Effect of preoperative pregabalin on postoperative pain relief in thyroidectomy patients: A prospective observational study.
Effective management of postoperative pain leads to increased patient satisfaction, earlier mobilization, reduced hospital stay and costs. One of the methods used for management of postoperative pain is preemptive analgesia-blockade of afferent nerve fibers before a painful stimulus. It modifies peripheral and central nervous system processing of noxious stimuli and reduces postoperative opioid consumption. In this study, we sought to determine whether the preoperative use of pregabalin reduced postoperative pain and morphine consumption in thyroidectomy. The observation was conducted on patients undergoing thyroidectomy surgery in two groups of 30 each. Of the two groups, one received a single oral dose of pregabalin 1 h preoperatively. Both the group of patients undergoes anesthesia in a similar manner. Following surgery the efficacy of the preoperative dose of pregabalin is observed by measuring the total opioid consumption 6 h postoperatively and assessing verbal numeric pain scales. The mean time to request of rescue analgesia in pregabalin group was 322.07 ± 69.106 min when compared to morphine group 256.33 ± 111.978 min (P < 0.05). The mean pain scores in the postoperative period were also significantly lower in patients receiving pregabalin. Single oral dose of pregabalin was effective in reducing acute postoperative pain in thyroidectomy patients. It prolongs the time to the request of rescue analgesia and also results in lower postoperative pain scores in the immediate postoperative period. However a statistically significant low opioid consumption could not be proved.


[Noninvasive tests of atherosclerotic burden in asymptomatic people with high cardiovascular risk].
Objective of cardiovascular prevention to reduce the risk of major cardiovascular events and morbidity and prolong the quality of life. Strategy of prevention is identification of high risk individuals, and action to reduce their risk factors levels. Noninvasive tests such as carotis artery duplex scanning, ultrasound-based endothelial function studies, ankle-brachial blood pressure ratios, coronary calcium score by electron-beam CT, and high-sensitivity testing for C-reactive protein offer the potential for directly and indirectly measuring atherosclerosis in asymptomatic people. If a patient is found to have abnormal non-invasive test, this patient can be elevated to a higher risk category.


Topological phonon modes and their role in dynamic instability of microtubules.
Microtubules (MTs) are self-assembled hollow protein tubes playing important functions in live cells. Their building block is a protein called tubulin, which self-assembles in a particulate 2 dimensional lattice. We study the vibrational modes of this lattice and find Dirac points in the phonon spectrum. We discuss a splitting of the Dirac points that leads to phonon bands with nonzero Chern numbers, signaling the existence of topological vibrational modes localized at MTs edges, which we indeed observe after explicit calculations. Since these modes are robust against the large changes occurring at the edges during the dynamic cycle of the MTs, we can build a simple mechanical model to illustrate how they would participate in this phenomenon.


Einstein-Podolsky-Rosen correlations via dissociation of a molecular Bose-Einstein condensate.
Recent experimental measurements of atomic intensity correlations through atom shot noise suggest that atomic quadrature phase correlations may soon be measured with a similar precision. We propose a test of local realism with mesoscopic numbers of massive particles based on such measurements. Using dissociation of a Bose-Einstein condensate of diatomic molecules into bosonic atoms, we demonstrate that strongly entangled atomic beams may be produced which possess Einstein-Podolsky-Rosen (EPR) correlations in field quadratures in direct analogy to the position and momentum correlations originally considered by EPR.


[Toxocara infections in childhood in relation to reactive arthritis].
Reactive arthritis belongs to a group of rheumatoid diseases known as seronegative spondylarthritis or spondarthropathies. Of many reactive arthritis-evoking agents, the authors focused on larval toxocarosis. The authors describe a child with high anti-Toxocara antibody and circulating antigen titres in combination with acute Chlamydia infection, which may have caused reactive arthritis in this immunologically impaired organism. This is evidence of the coincidence of different pathological factors manifested by reactive affection of the knee joint.


Stable sonoluminescence within a water hammer tube.
The sonoluminescence (SL) from the collapse of a single gas bubble within a liquid can be produced repetitively using an acoustic resonator. An alternative technique using a water hammer tube, producing SL from bubbles of greater size, is described here. A sealed vertical tube partly filled with a liquid and a gas at low pressure is subjected to vertical vibrations. The oscillation of the pressure within the liquid column, due to inertial forces, excites cavitation bubbles to grow and collapse. Rotation is used to confine the bubbles to the axis of the tube. Bright SL emissions were observed in a number of liquids. Repetitive emission was produced from bubbles in condensed phosphoric acid. Bubbles of 0.4 mm ambient radius (containing 2x 10(14) xenon atoms) were excited by vibration at 35 Hz. Approximately 10(12) photons were emitted per collapse in the range 400-700 nm (over four orders of magnitude greater than the brightest SL reported previously), corresponding to a 1% efficiency of the conversion of mechanical energy into light.


Sumoylation regulates protein dynamics during meiotic chromosome segregation in C. elegans oocytes.
Oocyte meiotic spindles in most species lack centrosomes and the mechanisms that underlie faithful chromosome segregation in acentrosomal meiotic spindles are not well understood. In C. elegans oocytes, spindle microtubules exert a poleward force on chromosomes that is dependent on the microtubule-stabilising protein CLS-2, the orthologue of the mammalian CLASP proteins. The checkpoint kinase BUB-1 and CLS-2 localise in the central spindle and display a dynamic localisation pattern throughout anaphase, but the signals regulating their anaphase-specific localisation remains unknown. We have shown previously that SUMO regulates BUB-1 localisation during metaphase I. Here, we found that SUMO modification of BUB-1 is regulated by the SUMO E3 ligase GEI-17 and the SUMO protease ULP-1. SUMO and GEI-17 are required for BUB-1 localisation between segregating chromosomes during early anaphase I. We also show that CLS-2 is subject to SUMO-mediated regulation; CLS-2 precociously localises in the midbivalent when either SUMO or GEI-17 are depleted. Overall, we provide evidence for a novel, SUMO-mediated control of protein dynamics during early anaphase I in oocytes.


Hormone-activated estrogen receptors in annelid invertebrates: implications for evolution and endocrine disruption.
As the primary mediators of estrogen signaling in vertebrates, estrogen receptors (ERs) play crucial roles in reproduction, development, and behavior. They are also the major mediators of endocrine disruption by xenobiotic pollutants that mimic or block estrogen action. ERs that are sensitive to estrogen and endocrine disrupters have long been thought to be restricted to vertebrates: although there is evidence for estrogen signaling in invertebrates, the only ERs studied to date, from mollusks and cephalochordates, have been insensitive to estrogen and therefore incapable of mediating estrogen signaling or disruption. To determine whether estrogen sensitivity is ancestral or a unique characteristic of vertebrate ERs, we isolated and characterized ERs from two annelids, Platynereis dumerilii and Capitella capitata, because annelids are the sister phylum to mollusks and have been shown to produce and respond to estrogens. Functional assays show that annelid ERs specifically activate transcription in response to low estrogen concentrations and bind estrogen with high affinity. Furthermore, numerous known endocrine-disrupting chemicals activate or antagonize the annelid ER. This is the first report of a hormone-activated invertebrate ER. Our results indicate that estrogen signaling via the ER is as ancient as the ancestral bilaterian animal and corroborate the estrogen sensitivity of the ancestral steroid receptor. They suggest that the taxonomic scope of endocrine disruption by xenoestrogens may be very broad and reveal how functional diversity evolved in a gene family central to animal endocrinology.


The statics of cervical traction.
The statics of a sliding body was used to study the distribution of forces during the application of cervical traction in supine patients. This theoretical analysis was completed using a dynamometer to determine the static friction between bed surface and patient head. Therefore, we measured the head weight in 12 inpatients and the minimum force that causes impending motion of the head on the bed surface. The static friction coefficient was calculated from the ratio of the two quantities. The forces acting on the cervical spine were determined by inserting the former data into a specifically designed algorithm that forecasted a progressively increasing traction angle. The coefficient of static friction was 0.62, whereas the maximum available force acting on the cervical spine was obtained with a 35 degrees traction inclination. In contrast, the forces dissipated by the plane progressively decreased with larger angles.


The Nature and Impact of Side Reactions in Glyme-based Sodium-Oxygen Batteries.
Although Na-O2 batteries have a low overpotential and good capacity retention, degradation reactions of glyme-based electrolytes are the primary reason for inefficiency in cell performance. The discharge capacity is accounted for through analysis of the side-products. Although sodium superoxide is the primary product (90 % theoretical), quantitative and qualitative evaluation of the side-products (using (1) H NMR, iodometric titration, and on-line mass spectrometry) shows the presence of sodium acetate (∼3.5 %), and three-fold less sodium formate, methoxy (oxo)acetic anhydride, and sodium carbonate. Our reaction mechanism proposes two paths for their formation. Because the side-products are not fully removed during oxidation, they accumulate on the cathode upon cycling. Resting the cell at open circuit potential during discharge results in consumption of the superoxide through the reaction with diglyme, which greatly increases the fraction of side products, as also confirmed by ex situ reaction studies. These findings have implications in the search for more stable electrolytes.


Effect of sour tea (Lipicom) pill versus captopril on the treatment of hypertension.
Herbal medicines are traditionally prescribed to manage blood pressure. We aimed to evaluate effect of sour tea pill containing the herb's extract versus captopril on the treatment of hypertension. In our crossover clinical trial 20 patients were enrolled in the study and advised for life style modification then the participants were randomly divided into 2 groups. Sour tea pills was prescribed at a dose of 500 mg and captopril at a dose of 12.5 mg twice daily. In order to improve precision and final measurement, ambulatory blood pressure monitoring (ABPM) was performed both prior and after measuring the hypertension in 2 successive visits. After 6 weeks of therapy, the methods changed and 6 weeks later ABPM was performed three times (baseline, at end of the 6th and 12th week). The 2 groups were merged together before data analysis. Of the 20 patients, 13 (65%) were male and 7 (35%) were female. No significant difference of sex, age, and job was detected between 2 groups (P ≥ 0.05). Mean decreasing in systolic blood pressure was 7.75 ± 8.3 and 13.3 ± 16.1 mm Hg in the captopril and sour tea groups, respectively. Also, mean decline in diastolic blood pressure decreases was 2.15 ± 4.14 and 5.8 ± 7.8 mm Hg for captopril and sour tea groups, respectively. No side effect was observed in the sour tea pill group in the study. According to the effect of sour tea pill on decreasing blood pressure, without giving priority over captopril, sour tea pill containing the herb's extract can be prescribed as an adjuvant therapy for lowering the prescribed dosage of captopril.


What do we do about Helicobacter pylori?
Heliobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) cause ulcers by different mechanisms. Under some circumstances, patients infected with H pylori may be less prone to NSAID-associated ulcers than those who are H pylori-negative. Eradication trials have yielded differing results. However, those who have studied patients who have a past history of ulcer disease and are already established on NSAIDs have shown no benefit from H pylori eradication.


A two-site solid phase enzyme immunoassay for rat epidermal growth factor.
A sensitive and simple two-site enzyme immunoassay was developed for rat epidermal growth factor (rEGF), which was purified from male rat submaxillary glands. This system is based on the sandwiching of the antigen between anti-rat EGF IgG antibody coated on a polystyrene bead and anti-rat EGF Fab' antibody-linked peroxidase, whose activity was stable at 4 degrees C for 6 months. In this system, the rat EGF was detectable at a concentration of 2 pg/tube. No interference was observed by addition of human plasma. There was no cross-reactivity with mouse EGF, human EGF, or other substances with similar chemical structures.


Synthesis and processing of Escherichia coli TEM-beta-lactamase and Bacillus licheniformis alpha-amylase in E. coli: the role of signal peptidase I.
A mutant of Escherichia coli, in which signal peptidase I synthesis can be regulated, was constructed. The mutant was used to study the effects of signal peptidase I limitation on the synthesis and efficiency of processing of two proteins: the periplasmic E. coli TEM-beta-lactamase and Bacillus licheniformis alpha-amylase, which also accumulates in the periplasm of E. coli. Signal peptidase I limitation resulted in reduced rates of processing of pre-beta-lactamase and in strong inhibition of synthesis of alpha-amylase. The data suggest that beta-lactamase is processed post-translationally and that an intimate relationship exists between the synthesis and processing of alpha-amylase.


Effects of TiO2 and Ag nanoparticles on polyhydroxybutyrate biosynthesis by activated sludge bacteria.
Manufactured nanomaterials (MNMs) are increasingly incorporated into consumer products that are disposed into sewage. In wastewater treatment, MNMs adsorb to activated sludge biomass where they may impact biological wastewater treatment performance, including nutrient removal. Here, we studied MNM effects on bacterial polyhydroxyalkanoate (PHA), specifically polyhydroxybutyrate (PHB), biosynthesis because of its importance to enhanced biological phosphorus (P) removal (EBPR). Activated sludge was sampled from an anoxic selector of a municipal wastewater treatment plant (WWTP), and PHB-containing bacteria were concentrated by density gradient centrifugation. After starvation to decrease intracellular PHB stores, bacteria were nutritionally augmented to promote PHB biosynthesis while being exposed to either MNMs (TiO2 or Ag) or to Ag salts (each at a concentration of 5 mg L(-1)). Cellular PHB concentration and PhyloChip community composition were analyzed. The final bacterial community composition differed from activated sludge, demonstrating that laboratory enrichment was selective. Still, PHB was synthesized to near-activated sludge levels. Ag salts altered final bacterial communities, although MNMs did not. PHB biosynthesis was diminished with Ag (salt or MNMs), indicating the potential for Ag-MNMs to physiologically impact EBPR through the effects of dissolved Ag ions on PHB producers.


Sonic hedgehog, secreted by amacrine cells, acts as a short-range signal to direct differentiation and lamination in the zebrafish retina.
Neurogenesis in the zebrafish retina occurs in several waves of differentiation. The first neurogenic wave generates ganglion cells and depends on hedgehog (hh) signaling activity. Using transgenic zebrafish embryos that express GFP under the control of the sonic hedgehog (shh) promoter, we imaged the differentiation wave in the retina and show that, in addition to the wave in the ganglion cell layer, shh expression also spreads in the inner nuclear layer. This second wave generates amacrine cells expressing shh, and although it overlaps temporally with the first wave, it does not depend on it, as it occurs in the absence of ganglion cells. We also show that differentiation of cell types found in the inner and outer nuclear layers, as well as lamination of the retina, depends on shh. By performing mosaic analysis, we demonstrate that Shh directs these events as a short-range signal within the neural retina.


Denosumab: Current Use in the Treatment of Primary Bone Tumors.
Denosumab, a human monoclonal antibody that inhibits bone resorption by binding on the receptor activator of the nuclear factor kappa-β ligand, has recently emerged as an additional option in the treatment of musculoskeletal osteolytic tumors. This article focuses on the recent literature regarding the effectiveness of denosumab in the management of giant cell tumor, multiple myeloma, aneurysmal bone cyst, and osteosarcoma. The mechanism of action of denosumab in the management of these tumors and the associated side effects are discussed in detail. [ Orthopedics. 2017; 40(4):204-210.].


A xylose-stimulated xylanase-xylose binding protein chimera created by random nonhomologous recombination.
Saccharification of lignocellulosic material by xylanases and other glycoside hydrolases is generally conducted at high concentrations of the final reaction products, which frequently inhibit the enzymes used in the saccharification process. Using a random nonhomologous recombination strategy, we have fused the GH11 xylanase from Bacillus subtilis (XynA) with the xylose binding protein from Escherichia coli (XBP) to produce an enzyme that is allosterically stimulated by xylose. The pT7T3GFP_XBP plasmid containing the XBP coding sequence was randomly linearized with DNase I, and ligated with the XynA coding sequence to create a random XynA-XBP insertion library, which was used to transform E. coli strain JW3538-1 lacking the XBP gene. Screening for active XBP was based on the expression of GFP from the pT7T3GFP_XBP plasmid under the control of a xylose inducible promoter. In the presence of xylose, cells harboring a functional XBP domain in the fusion protein (XBP+) showed increased GFP fluorescence and were selected using FACS. The XBP+ cells were further screened for xylanase activity by halo formation around xylanase producing colonies (XynA+) on LB-agar-xylan media after staining with Congo red. The xylanase activity ratio with xylose/without xylose in supernatants from the XBP+/XynA+ clones was measured against remazol brilliant blue xylan. A clone showing an activity ratio higher than 1.3 was selected where the XynA was inserted after the asparagine 271 in the XBP, and this chimera was denominated as XynA-XBP271. The XynA-XBP271 was more stable than XynA at 55 °C, and in the presence of xylose the catalytic efficiency was ~3-fold greater than the parental xylanase. Molecular dynamics simulations predicted the formation of an extended protein-protein interface with coupled movements between the XynA and XBP domains. In the XynA-XBP271 with xylose bound to the XBP domain, the mobility of a β-loop in the XynA domain results in an increased access to the active site, and may explain the observed allosteric activation. The approach presented here provides an important advance for the engineering enzymes that are stimulated by the final product.


Clustered tuberculosis in a low-burden country: nationwide genotyping through 15 years.
Molecular genotyping of Mycobacterium tuberculosis has proved to be a powerful tool in tuberculosis surveillance, epidemiology, and control. Based on results obtained through 15 years of nationwide IS6110 restriction fragment length polymorphism (RFLP) genotyping of M. tuberculosis cases in Denmark, a country on the way toward tuberculosis elimination, we discuss M. tuberculosis transmission dynamics and point to areas for control interventions. Cases with 100% identical genotypes (RFLP patterns) were defined as clustered, and a cluster was defined as cases with an identical genotype. Of 4,601 included cases, corresponding to 76% of reported and 97% of culture-verified tuberculosis cases in the country, 56% were clustered, of which 69% were Danes. Generally, Danes were more often in large clusters (≥ 50 persons), older (mean age, 45 years), and male (male/female ratio, 2.5). Also, Danes had a higher cluster frequency within a 2-year observation window (60.8%), and higher clustering rate of new patterns over time, compared to immigrants. A dominant genotype, cluster 2, constituted 44% of all clustered and 35% of all genotyped cases. This cluster was primarily found among Danish males, 30 to 59 years of age, often socially marginalized, and with records of alcohol abuse. In Danes, cluster 2 alone was responsible for the high cluster frequency level. Immigrants had a higher incidence of clustered tuberculosis at a younger age (0 to 39 years). To achieve tuberculosis elimination in Denmark, high-risk transmission environments, like the cluster 2 environment in Danes, and specific transmission chains in immigrants in the capital area, e.g., homeless/socially marginalized Somalis/Greenlanders, often with alcohol abuse, must be targeted, including groups with a high risk of reactivation.


Inflammatory bowel diseases and primary sclerosing cholangitis: hepatic and pancreatic side effects due to azathioprine.
In up to 80% of cases primary sclerosing cholangitis (PSC) is associated with inflammatory bowel diseases (IBD). The efficacy of azathioprine (AZA), in the maintenance of remission of IBD has been suggested by several studies. However, AZA tends to exter varied well-known toxicity. Since the rate of hepato-pancreatic side-effects in patients with IBD and PSC is still unclear, we investigated this issue. Consecutive subjects who underwent Outpatient Clinic admission for both IBD and PSC were included. Both conditions were diagnosed according to International Guidelines. Data of 43 patients were elaborated. Twelve of them underwent therapy with AZA. Five (41.7%) presented hepatic (n=4) or pancreatic toxicity. Eighty percent of the patients with hepato-pancreatic reactions versus 28.6% of those without (p < 0.001) were males, with 60% affected by ulcerative colitis and 40% by Crohn's disease versus 57% and 43%, respectively. Forty percent of patients with reactions versus 43% of those without needed an operation for IBD, and the same percentage underwent orthotopic liver transplantation, with a 100% versus 66.7% (p < 0.001) need of second transplantation. Colonic neoplasia (20%) was detected only in the former group while cholangiocarcinoma (28.6%) only in the latter. The occurrence of hepato-pancreatic reactions from AZA in our caseload is higher (41.7%) compared to that reported in literature (4%). Therefore, the presence of PSC, in association to IBD, may strongly affect AZA tolerability compared to presence of IBD only.


CD14 expression and soluble CD14 after segmental allergen provocation in atopic asthma.
Allergic asthma is associated with the recruitment of activated inflammatory cells after allergen challenge. Surface expression of CD14 has been proposed as a marker of cell activation and differentiation. We therefore measured CD14 expression on activated macrophages and granulocytes as well as soluble CD14 (sCD14) concentrations in peripheral blood and bronchoalveolar lavage (BAL) following segmental allergen provocation (SAP) with individually standardized doses of allergen in eight patients with allergic asthma. Two segments of the right lung were challenged with allergen. Two segments of the left lung, into which saline was instilled, served as controls. CD14 expression on macrophages and granulocytes was determined by flow-cytometry and concentrations of interleukins and sCD14 were analysed by enzyme-linked immunosorbent assay (ELISA) 10 min and 18 h after challenge. Soluble CD14 concentrations remained unchanged in BAL fluid after saline challenge and 10 min after SAP, but increased significantly 18 h after SAP. Although macrophage numbers increased 18h after SAP, CD14 expression on these cells did not change. Unlike macrophages, granulocyte numbers correlated with sCD14 levels 18 h after SAP while their CD14 expression decreased significantly. Furthermore, sCD14 correlated with interleukin (IL)-13 concentrations 18 h after SAP. An increase in soluble CD14 can be observed 18 h but not 10 min after segmental allergen provocation suggesting local release of this surface antigen. Our findings imply that CD14-mediated cell activation following segmental allergen provocation could play a role in asthmatic inflammation.


Neurotropin reverses paclitaxel-induced neuropathy without affecting anti-tumour efficacy.
Paclitaxel is a commonly used anticancer drug, but it frequently causes peripheral neuropathy. Neurotropin, a non-protein extract from inflamed rabbit skin inoculated with vaccinia virus, has been used to treat various chronic painful conditions. In the present study, we investigated the effect of neurotropin on the paclitaxel-induced neuropathy in rats. Repeated administration of paclitaxel induced mechanical allodynia, cold hyperalgesia, and motor dysfunction. These neuropathies were mostly reversed by the repeated administration of neurotropin. Furthermore, neurotropin ameliorated the paclitaxel-induced axonal degeneration in cultured PC12 and rat dorsal root ganglion cells, and in rat sciatic nerve. In addition, neurotropin did not affect the microtubule aggregation or anti-tumour effect induced by paclitaxel in the tumour cell lines or tumour cells-implanted mice. These results suggest that neurotropin reverses the paclitaxel-induced neuropathy without affecting anti-tumour activity of paclitaxel, and therefore may be useful for the paclitaxel-induced neuropathy in clinical settings.


An evaluation of risk factors for in-patient falls in acute and rehabilitation elderly care wards.
Falls occurring in elderly in-patients during periods of hospitalization are common, and attempts have been made to predict and prevent them based on risk factor analysis. These have not looked extensively at specific elderly care wards. We have investigated in-patient falls in mixed acute and rehabilitation elderly care wards in a case-controlled study. Fifty fallers were paired with fifty non-fallers, and their risk factors for falling evaluated. Only three risk factors were significantly more common in the fallers. These were: a previous history of falls; the presence of confusion/disorientation, and needing help to toilet/incontinence/diarrhoea. Prediction of falls based on the presence of the first two of these risk factors gives a sensitivity of 68% and a specificity of 88%. A risk factor approach to the prediction of falls in an in-patient elderly care setting seems to be less practical than was previously hoped.


Draft Whole-Genome Sequences of 10 Serogroup O6 Enterotoxigenic Escherichia coli Strains.
Entertotoxigenic Escherichia coli (ETEC) is a major cause of global diarrhea, resulting in approximately 200 million occurrences and 300,000 to 400,000 deaths annually, primarily in children under the age of five. Here, we announce the release of the draft genomes of 10 ETEC isolates belonging to serogroup O6.


Creating natural-looking removable prostheses: combining art and science to imitate nature.
Patient awareness of dental appearance has increased, resulting in more demanding esthetic requests. There is also strong evidence that increased esthetics is highly significant for complete denture acceptance and success. Taking notice of patients' perceptions of natural appearance and esthetics, the clinician can incorporate their preferences in the construction of individualized dentures that will be harmonized with their facial characteristics. Despite the evolution of materials and techniques, the vast majority of dentures still fail to look natural. Thus, producing prostheses that defy detection and successfully restore the appearance of edentulous patients remains a challenge for the clinician. This paper presents a clinical case where immediate loading of implants supporting a mandibular overdenture was combined with an opposing conventional maxillary denture to satisfy the high functional and esthetic demands of the patient. It also emphasizes the individualized esthetic performance through customization during their fabrication while taking into consideration the various clinical parameters affecting rehabilitation of the edentulous jaw. Implant-retained overdentures can significantly improve the patients' function. The esthetic performance of these restorations however, may not be satisfying the patients' expectations and demands. Customizing the artificial gingival areas and individual staining of the prefabricated acrylic teeth may improve the esthetic performance creating natural-looking removable prostheses.


[Influences of anesthetic method on post-cholecystectomy pain--a comparison between epidural and general anesthesia].
This study was designed to compare the influence of epidural anesthesia with that of general anesthesia on postoperative pain state and management. We studied 16 patients who underwent elective laparotomy-cholecystectomy with epidural anesthesia without general anesthesia or with general anesthesia (nitrous oxide-isoflurane). Following bolus epidural injection with 3 micrograms.kg-1 of buprenorphine in 0.25% bupivacaine 4-7 ml at the end of surgery, all patients received continuous epidural buprenorphine administration at the rate of 12 micrograms.h-1 for 48 hours. Pain relief was assessed for 72 hours after surgery using visual analogue scale. Postoperative rest pain of the epidural group remained at a lower state of pain than that of the general anesthesia group not only for 48 hours (P < 0.005) but also until 72 hours (P < 0.005) after surgery. We concluded that the epidural anesthesia produces a greater postoperative pain relief than general anesthesia.


Beyond diffusion-limited aggregation kinetics in microparticle suspensions.
Aggregation in nondiffusion limited colloidal particle suspensions follows a temporal power-law dependence that is consistent with classical diffusion limited cluster aggregation models; however, the dynamic scaling exponents observed in these systems are not adequately described by diffusion limited cluster aggregation models, which expect these scaling exponents to be constant over all experimental conditions. We show here that the dynamic scaling exponents for 10 microm particles increase with the particle concentration and the particle-particle free energy of interaction. We provide a semiquantitative explanation for the scaling behavior in terms of the long-ranged particle-particle interaction potential.


Positron emission tomography/computer tomography in gastrointestinal malignancies: current potential and challenges.
The use of 18F-Fluoro-D-deoxy-glucose -positron emission tomography/computed tomography (FDG-PET/CT) in gastrointestinal (GI)-malignancies may not be as straightforward as in many other cancers, but the potential is clearly there in select clinical settings. The challenges include the relative non-specificity of FDG, the variable degrees of physiologic FDG-uptake, and the heterogeneous FDG-uptake in different cell types within the GI-domain, which all together hamper the use in primary diagnostics. In general, the literature is older, heterogeneous, and based on stand-alone PET, which is now largely considered obsolete. There is emerging evidence for use of hybrid PET/CT, but the literature is still relatively sparse. The main indications are preoperative staging of distant metastases, not only in limited disease but also before curative treatment of limited metastatic disease. Controversies remain concerning liver metastases but improved technology boast well for the future role of FDG-PET/CT not least concerning equivocal findings on conventional imaging. In our opinion, an important upcoming indication is early response assessment, perhaps mostly in the neoadjuvant settings of upper GI-malignancies, but standardization of response assessment criteria is lacking before a more widespread implementation is feasible. Finally, there seems to be a significant role in recurrence detection, especially in CRC.


Imposing function down a (cupin)-barrel: secondary structure and metal stereochemistry in the αKG-dependent oxygenases.
The Fe(ii)/αketoglutarate (αKG) dependent oxygenases catalyze a diverse range of reactions significant in biological processes such as antibiotic biosynthesis, lipid metabolism, oxygen sensing, and DNA and RNA repair. Although functionally diverse, the eight-stranded β-barrel (cupin) and HX(D/E)XnH facial triad motifs are conserved in this super-family of enzymes. Crystal structure analysis of 25 αKG oxygenases reveals two stereoisomers of the Fe cofactor, Anti and Clock, which differ in the relative position of the exchangeable ligand position and the primary substrate. Herein, we discuss the relationship between the chemical mechanism and the secondary coordination sphere of the αKG oxygenases, within the constraints of the stereochemistry of the Fe cofactor. Sequence analysis of the cupin barrel indicates that a small subset of positions constitute the second coordination sphere, which has significant ramifications for the structure of the ferryl intermediate. The competence of both Anti and Clock stereoisomers of Fe points to a ferryl intermediate that is 5 coordinate. The small number of conserved close contacts within the active sites of αKG oxygenases can be extended to chemically related enzymes, such as the αKG-dependent halogenases SyrB2 and CytC3, and the non-αKG dependent dioxygenases isopenicillin N synthase (IPNS) and cysteine dioxygenase (CDO).


Cuff Leak Test and Airway Obstruction in Mechanically Ventilated Intensive Care Unit Patients: A Pilot Randomized Controlled Clinical Trial.
Rationale: Laryngeal edema is a known complication of endotracheal intubation that may cause airway obstruction upon extubation. The only test available to predict this complication is the cuff leak test (CLT). Objectives: Given the uncertainty of the CLT's clinical utility, we conducted the COMIC (Cuff Leak Test and Airway Obstruction in Mechanically Ventilated ICU Patients) pilot study to examine the feasibility of undertaking a larger trial. Methods: COMIC is a multicentered, parallel-group randomized trial performed in Canada, Saudi Arabia, and Poland. We enrolled mechanically ventilated adults admitted to the intensive care unit who were deemed ready for extubation. Those allocated to the intervention arm had the results of their CLT communicated to the healthcare team, who then decided to proceed with extubation or not. In those randomized to the control arm, the CLT results were not communicated to the healthcare team and patients were extubated, regardless of the CLT result. The primary outcomes focused on feasibility. Results: One hundred patients (56 in the intervention and 44 in the control arm) were enrolled. All feasibility criteria were met, including 1) recruitment rate of 7.6 patients/month, 2) consent rate of 88.3% (95% confidence interval [CI], 82.1-94.5%), and 3) protocol adherence of 98% (95% CI, 95-100%). There were two episodes of clinically significant stridor in the intervention group and four patients who required reintubation in each group. Conclusions: The results of the COMIC pilot trial support the feasibility of a larger trial to determine the effect of the CLT on reintubation and clinically important stridor.Clinical trial registered with www.clinicaltrials.gov (NCT03372707).


Syntabulin-mediated anterograde transport of mitochondria along neuronal processes.
In neurons, proper distribution of mitochondria in axons and at synapses is critical for neurotransmission, synaptic plasticity, and axonal outgrowth. However, mechanisms underlying mitochondrial trafficking throughout the long neuronal processes have remained elusive. Here, we report that syntabulin plays a critical role in mitochondrial trafficking in neurons. Syntabulin is a peripheral membrane-associated protein that targets to mitochondria through its carboxyl-terminal tail. Using real-time imaging in living cultured neurons, we demonstrate that a significant fraction of syntabulin colocalizes and co-migrates with mitochondria along neuronal processes. Knockdown of syntabulin expression with targeted small interfering RNA or interference with the syntabulin-kinesin-1 heavy chain interaction reduces mitochondrial density within axonal processes by impairing anterograde movement of mitochondria. These findings collectively suggest that syntabulin acts as a linker molecule that is capable of attaching mitochondrial organelles to the microtubule-based motor kinesin-1, and in turn, contributes to anterograde trafficking of mitochondria to neuronal processes.


Transoperative refusion: a simple and safe method in emergency surgery.
The objective is to reinforce the importance of blood reinfusion as a cheap, safe and simple method, which can be used in small hospitals, especially those in which there is no blood bank. Moreover, even with the use of devices that perform the collection and filtration of blood, more recent studies show that the cost-benefit ratio is much better when autologous transfusion is compared with blood transfusions, even when there is injury to hollow viscera and blood contamination. It is known that the allogeneic blood transfusion carries a number of risks to patients, among them are the coagulation disorders mediated by excess enzymes in the conserved blood, and deficiency in clotting factors, mainly the Factor V, the proacelerin. Another factor would be the risk of contamination with still unknown pathogens or that are not investigated during screening for selection of donors, such as the West Nile Fever and Creutzfeldt-Jacob, better known as "Mad Cow" disease. Comparing both methods, we conclude that blood autotransfusion has numerous advantages over heterologous transfusion, even in large hospitals. We are not against blood transfusions, just do not agree that the patient's own blood is discarded without making sure there will be enough blood in stock to get him out of the hemorrhagic shock.


[Simultaneous determination of five water-soluble vitamins in human serum by high performance liquid chromatography].
To establish a method for the simultaneous determination of 5 water-soluble vitamins including VB1, VB6, Nicotinic acid, Nicotinamide and Folic acid by high performance liquid chromatography. Methanol (200 microL) was added to 50 microL human blood sample to precipitate proteins. The sample was frozen (-18 degrees C) for 30 min, and then centrifuged at 8000 r/min for 8 min. The supernatant was subsequently applied to the solid-phase cartridge for further purification. The elute was collected and evaporated to 0.20 mL under nitrogen in a water bath at the temperature of 50 degrees C and finally 50 microL of the sample was injected onto HPLC column for analysis. The five water-soluble vitamins were determined under optimized condition of solid phase extraction and chromatograph. The optimized condition for solid phase extraction (SPE) was identified as: AGT cleanert ODS C18 column as SPE column and CH3OH (2.4 mL)-H2O (0.6 mL) mixed liquor as eluent, with a flow rate of elution of 0.5 mL/min. The optimized chromatographic condition was identified as, Phenomenex C18 Luna column (250 x 4.6 mm, 5 microm) as analytical column under a temperature of 20 degrees C and 0.05 mol/L potassium dehydrogenates phosphate buffer (pH 6.0) and methanol as gradient elution with mobile phase with a flow rate of 0.9 mL/min. The detection wavelength was 266 nm. The correlation coefficients for the standard curves were greater than 0.999 in the range from 0 to 100 ng (RSD < 5%). The detection limits (S/N 2) ranged from 0.076 to 0.170 microg/mL. The recovery rate ranged from 80.2% to 115.0%. Except for Nicotinamide, the other four vitamins were detected successfully in the blood sample. This quick and convenient method can be applied to the simultaneous determination of 4 water-soluble vitamins in human serum samples. But the sensitivity for detecting Nicotinamide needs to be improved.


Six novel nonsynonymous CYP1A2 gene polymorphisms: catalytic activities of the naturally occurring variant enzymes.
Six novel nonsynonymous nucleotide alterations were found in the cytochrome P450 1A2 gene in a Japanese population, which resulted in the following amino acid substitutions: T83M, E168Q, F186L, S212C, G299A, and T438I. These individuals were heterozygous for the amino acid substitutions. The potential functional alterations caused by the amino acid substitutions were characterized by a cDNA-mediated expression system using Chinese hamster V79 cells. Among the six CYP1A2 variants, F186L showed the most profound and statistically significant reduction in O-deethylation of phenacetin and 7-ethoxyresorufin. Kinetic analyses performed for the ethoxyresorufin O-deethylation revealed that the Vmax of the F186L variant was approximately 5% of that of the CYP1A2 wild type, despite a 5-fold lower Km value of the variant, the consequence of which was reduced enzymatic activity toward the substrate. Thus, for the first time, phenylalanine at residue 186 is suggested to be a critical amino acid for catalytic activity.


ANGSD: Analysis of Next Generation Sequencing Data.
High-throughput DNA sequencing technologies are generating vast amounts of data. Fast, flexible and memory efficient implementations are needed in order to facilitate analyses of thousands of samples simultaneously. We present a multithreaded program suite called ANGSD. This program can calculate various summary statistics, and perform association mapping and population genetic analyses utilizing the full information in next generation sequencing data by working directly on the raw sequencing data or by using genotype likelihoods. The open source c/c++ program ANGSD is available at http://www.popgen.dk/angsd . The program is tested and validated on GNU/Linux systems. The program facilitates multiple input formats including BAM and imputed beagle genotype probability files. The program allow the user to choose between combinations of existing methods and can perform analysis that is not implemented elsewhere.


Prognosis Model of Advanced Non-Small-Cell Lung Cancer Based on Max-Min Hill-Climbing Algorithm.
A safer and more effective treatment is need for the comprehensive treatment based on chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). The max-min hill-climbing (MMHC) is a common algorithm for disease prediction. This study is aimed at analyzing the efficacy of the MMHC algorithm in prognosis evaluation of advanced NSCLC. In this study, the prognosis model of lung cancer was first established by the MMHC algorithm. Then, according to the MMHC algorithm results, 40 patients with advanced NSCLC were divided into the research group and control group before anlotinib hydrochloride capsule combined with pemetrexed disodium chemotherapy. The diameter of solid tumor lesions, objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) was compared between the two groups. The results showed that the MMHC model has a higher prediction accuracy of survival status of lung cancer patients. Under the guidance of the model, the research group has a smaller diameter of primary foci and metastatic foci, a higher ORR, DCR, and a longer PFS than the control group (P < 0.05). We can conclude that the MMHC algorithm can guide the maintenance treatment of advanced NSCLC, which is conducive to the prognosis judgment and treatment cost control.


Characteristics of two questionnaires used to assess interprofessional learning: psychometrics and expert panel evaluations.
Interprofessional learning activities are included in many curricula but are difficult to assess. For languages that are not widely spoken such as Swedish, few validated questionnaires exist that relate to interprofessional outcomes. Therefore, the aim was to examine two such questionnaires in relation to interprofessional competence domains. Psychometric characteristics, such as homogeneity of items and internal consistency, were assessed for the Swedish versions of the Jefferson Scale of Attitudes Towards Physician-Nurse Collaboration (JSAPNC) and the Readiness for Interprofessional Learning Scale (RIPLS). The questionnaires were distributed directly following IPL activities. Mokken scale analysis based on Loevinger's coefficient for homogeneity and Cronbach's alpha were used to evaluate the scales. Two expert panels performed a qualitative analysis of items in relation to four internationally defined interprofessional competences. In total, 88 and 84 responded to the JSAPNC and RIPLS questionnaires, respectively. Estimates of homogeneity were low for both the JSAPNC (H = 0.16) and the RIPLS (H = 0.21). Reliabilities were weak (0.62 and 0.66, respectively) for the total scales. The expert panels categorised 68% of items into similar competence domains. However, their discussion revealed ambiguous wordings and imbalances in the two questionnaires in relation to domains. Interprofessional competence domains are defined but few validated tools exist to assess them. Examined tools relating to interprofessional learning in Swedish do not qualify for assessing overarching IPL outcomes, and summed scores from these tools should be used with caution.


Immunologic responses to conjugates of antigen E in patients with ragweed hay fever.
Allergens conjugated with several simple repeating polymers have reduced allergenicity in man, but large doses retain the ability to suppress ongoing allergen-specific IgE synthesis in strains of high-responder mice. To determine whether suppression of IgE antibodies could be induced in man, preliminary trials of immunologic responses to conjugates in man were carried out in ragweed hay fever patients treated with antigen E (AgE) coupled to methoxypolyethylene glycols ( MPEGs ) of 5000 and 2000 daltons, lauryloxypolyethylene glycol of 1200 daltons, and a random copolymer of D-lysine and D-glutamic acid of 69,000 daltons. In varying degrees all these conjugates had reduced allergenicity by basophil histamine release when these conjugates were compared with native AgE and could suppress IgE response in mice. Patients received one of these conjugates or native AgE in a series of subcutaneous injections and were observed for allergic reactions. The conjugates induced a lower rate of systemic reaction than native AgE but failed to induce early suppression of IgE antibodies. Instead, early rises in IgE antibody occurred in the several groups and were followed by a slow decline during a year or more that was similar to that observed with standard immunotherapy. Because the conjugates eventually caused local and systemic allergic reactions as the dose was raised, it was not possible to test the IgE-suppressive effects at doses similar to those used in mice. In contrast, rapid sustained rises in IgG antibodies occurred in all groups. The MPEG conjugates appeared to be more effective than native AgE in this regard. The reduced rate of systemic reaction and rapid rise in IgG antibody that was noted with MPEG conjugates make them worth further exploration as agents for immunotherapy.


Participation of rec genes of Escherichia coli K 12 in W-reactivation of UV-irradiated phage lambda.
The effect of the recombinational deficiency on W-reactivation of UV-damaged phage lambda was explored. In this paper we show that W-reactivation is reduced by the recB21 and recF143 mutations after bleomycin (BM) and UV treatment. Combination of these mutations in the recB21recF143 double mutant blocks W-reactivation completely after BM induction, but leaves residual W-reactivation ability after UV-irradiation, which is abolished by the introduction of uvrB deficiency (delta(uvrB-chlA]. W-reactivation has been rendered constitutive in recB21C22sbcB15, but the efficiency of reactivation remained virtually constant over the range of BM and UV doses, indicating the role of the RecBC(D) enzyme in W-reactivation.


Experimental evidence for IS1294b-mediated transposition of the blaCMY-2 cephalosporinase gene in Enterobacteriaceae.
The objective of this study was to investigate whether the insertion sequence IS1294b (IS91 family) is able to mobilize the blaCMY-2 gene and its adjacent regions from one replicon to another. Klebsiella pneumoniae Kp2735 was typed by MLST and its plasmid content was examined by S1-PFGE and PCR-based replicon typing. The genetic blaCMY-2 environment was analysed after cloning experiments and sequencing. Transposition assays were performed with an inactivation strategy based on the sacB gene, which confers sucrose-dependent lethality. Kp2735 (ST215) exhibited high-level resistance to ceftazidime owing to the presence of the cephalosporinase CMY-2. The blaCMY-2 gene was located on an IncI1 ST156 plasmid, p2735, of ∼95 kb. Analysis of the genetic environment revealed, upstream of blaCMY-2, the presence of ISEcp1 interrupted by IS1294b and, downstream of blaCMY-2, a region of 1395 bp belonging to the backbone of IncA/C replicons, suggesting a possible DNA transfer between the two plasmids. We showed that IS1294b is able to mobilize blaCMY-2 and its adjacent regions efficiently on the recipient plasmid with a mean frequency of 5.9%. This transfer was due to a one-ended transposition mechanism, implying the non-recognition of its terIS end. Our experimental data demonstrate for the first time, to our knowledge, the mobilization of a β-lactamase gene mediated by a member of the IS91 family and highlight the important role of this mobile genetic element in the spread of antibiotic resistance genes.


Prion fibrillization is mediated by a native structural element that comprises helices H2 and H3.
Aggregation and misfolding of the prion protein (PrP) are thought to be the cause of a family of lethal neurodegenerative diseases affecting humans and other animals. Although the structures of PrP from several species have been solved, still little is known about the mechanisms that lead to the misfolded species. Here, we show that the region of PrP comprising the hairpin formed by the helices H2 and H3 is a stable independently folded unit able to retain its secondary and tertiary structure also in the absence of the rest of the sequence. We also prove that the isolated H2H3 is highly fibrillogenic and forms amyloid fibers morphologically similar to those obtained for the full-length protein. Fibrillization of H2H3 but not of full-length PrP is concomitant with formation of aggregates. These observations suggest a "banana-peeling" mechanism for misfolding of PrP in which H2H3 is the aggregation seed that needs to be first exposed to promote conversion from a helical to a beta-rich structure.


Investigation of chlamydophilosis from naturally infected cats.
Chlamydophila felis, formerly known as Chlamydia psittaci var. felis, is frequently associated with ocular, respiratory, and occasionally reproduction tract infections. Even though the infection is sometimes asymptomatic, it potentially results in a latent immunosuppressive infection. This study aimed to identify occurrences of feline chlamydophilosis, rarely reported in cats in Indonesia. The observation was conducted in three cats with clinical signs of Cp. felis infection, particularly relapsing conjunctivitis. The cats' histories were recorded based on owners' information. Conjunctival swabs were sampled for cytology examination and molecular assay detection. A phylogenetic tree was generated using MEGA-X software to reveal group clustering. A post-mortem examination was performed on the cat that died during an examination. Cp. felis was detected in both cytological examination and polymerase chain reaction assay. The phylogenetic tree demonstrated that the Cp. felis isolated in this study clustered with several other isolates from the other countries. Cp. felis can be isolated from cats with different clinical manifestations and levels of severity. The chronic fatal infection demonstrated interstitial broncho-pneumonia under histopathological examination. Molecular assay of Cp. felis is always recommended to obtain a definitive diagnosis of feline chlamydophilosis since the disease can have various clinical manifestations. Even though it may be subclinical and is often not fatal, an infected cat may be a carrier that could spread the pathogen in the surrounding environment. Serious disease management is suggested to avoid high costs associated with regularly relapsing disease.


A Proposal to Optimize Satisfaction and Adherence in Group Fitness Programs For Patients With Major Depressive Disorder.
It is clear that exercise can be a source of great support for patients with major depressive disorder. However, it is important to recognize that several multifactorial and intersecting challenges are associated with exercise for this patient population. Group fitness programs for this patient population have the potential to be cost-effective while serving as an avenue of social interaction for participants. From an administrative perspective, it is challenging to balance satisfaction and adherence in group fitness programs targeting patients with major depressive disorder. This article presents a proposal that highlights what the challenges may look like in practice and discusses 3 strategies for improving satisfaction and adherence with a group fitness program: diagnosis and needs assessment, exercise diversity, and ongoing evaluation.


Assessment of the heparin-binding AN69 ST hemodialysis membrane: II. Clinical studies without heparin administration.
Binding polyanionic unfractionated heparin over the modified AN69 polyacrylonitrile membrane, the surface electronegativity of which has been neutralized by polyethyleneimine (AN69-ST), renders the membrane more hemocompatible. This property was tested in two groups of long-term hemodialysis patients. Results were rated as massive or partial clotting of a dialyzer at the end of the session. Group I patients were included in a prospective, cross-over study comparing standard dialysis with hemodialysis without systemic administration of unfractionated heparin (n = 12, 123 sessions). In all instances, priming was made with 2 I saline containing 5,000 IU/l heparin. Only patchy or partial clotting was observed in 11% and 39% of the sessions with standard and heparin-free administration, respectively. Group II patients were included in an open, observational pilot study testing the effects of the heparin-coated membrane, without systemic administration of heparin, in patients at high risk of bleeding (n = 68, 331 sessions). Massive clotting was observed in six sessions only (less than 2%) and normal or slightly patchy dialyzers were found in 88% of the sessions. It is concluded that the dialysis AN69 ST membrane, after adequate priming at bedside, can be used without systemic administration of heparin for hemodialysis in patients at high risk of bleeding.


Differential Effects of E2 on MAPK Activity in the Brain and Heart of Aged Female Rats.
Aging and the coincident loss of circulating estrogens at menopause lead to increased risks for neurological and cardiovascular pathologies. Clinical studies show that estrogen therapy (ET) can be beneficial in mitigating these negative effects, in both the brain and heart, when it is initiated shortly after the perimenopausal transition. However, this same therapy is detrimental when initiated >10 years postmenopause. Importantly, the molecular mechanisms underlying this age-related switch in ET efficacy are unknown. Estrogen receptors (ERs) mediate the neuroprotective and cardioprotective functions of estrogens by modulating gene transcription or, non-genomically, by activating second messenger signaling pathways, such as mitogen activated protein kinases (MAPK). These kinases are critical regulators of cell signaling pathways and have widespread downstream effects. Our hypothesis is that age and estrogen deprivation following menopause alters the expression and activation of the MAPK family members p38 and ERK in the brain and heart. To test this hypothesis, we used a surgically induced model of menopause in 18 month old rats through bilateral ovariectomy (OVX) followed by an acute dose of 17β-estradiol (E2) administered at varying time points post-OVX (1 week, 4 weeks, 8 weeks, or 12 weeks). Age and E2 treatment differentially regulated kinase activity in both the brain and heart, and the effects were also brain region specific. MAPK signaling plays an integral role in aging, and the aberrant regulation of those signaling pathways might be involved in age-related disorders. Clinical studies show benefits of ET during early menopause but detrimental effects later, which might be reflective of changes in kinase expression and activation status.


HIV-1 and its resistance to peptidic carbohydrate-binding agents (CBAs): an overview.
The glycoproteins on the surfaces of enveloped viruses, such as HIV, can be considered as a unique target for antiviral therapy. Different carbohydrate-binding agents (CBAs) target specific glycans present on viral glycoproteins of enveloped viruses. It has been shown that long-term CBA pressure in vitro can result in mutant HIV-1 isolates with several N-linked glycan deletions on gp120. These studies demonstrated that mainly high-mannose type glycans are deleted. However, interestingly, N241, N262 and N356 on gp120 have never been found to be affected after prolonged CBA exposure. Here, we review the mutation and (cross)-resistance profiles of eleven specific generated CBA-resistant HIV-1 strains. We observed that the broad-neutralizing anti-carbohydrate binding mAb 2G12 became completely inactive against all the generated CBA-resistant HIV-1 clade B isolates. In addition, all of the CBAs discussed in this review, with the exception of NICTABA, interfered with the binding of 2G12 mAb to gp120 expressed on HIV-1-infected T cells. The cross-resistance profiles of mutant HIV-1 strains are varying from increased susceptibility to very high resistance levels, even among different classes of CBAs with dissimilar sugar specificities or binding moieties [e.g., α(1,3), α(1,2), α(1,6)]. Recent studies demonstrated promising results in non-topical formulations (e.g., intranasally or subcutaneously), highlighting their potential for prevention (microbicides) and antiviral therapy.


The neurophysiology of ketamine: an integrative review.
The drug ketamine has been extensively studied due to its use in anaesthesia, as a model of psychosis and, most recently, its antidepressant properties. Understanding the physiology of ketamine is complex due to its rich pharmacology with multiple potential sites at clinically relevant doses. In this review of the neurophysiology of ketamine, we focus on the acute effects of ketamine in the resting brain. We ascend through spatial scales starting with a complete review of the pharmacology of ketamine and then cover its effects on in vitro and in vivo electrophysiology. We then summarise and critically evaluate studies using EEG/MEG and neuroimaging measures (MRI and PET), integrating across scales where possible. While a complicated and, at times, confusing picture of ketamine's effects are revealed, we stress that much of this might be caused by use of different species, doses, and analytical methodologies and suggest strategies that future work could use to answer these problems.