An immunogenic 30-kDa surface antigen of pathogenic clinical isolates of Entamoeba histolytica.
A 30-kDa surface antigen was identified by Western blots with human immune sera in all 15 isolates of E. histolytica from patients with invasive amebiasis (pathogenic) but not in 15 strains from asymptomatic patients (nonpathogenic). This antigen is highly immunogenic in naturally infected humans and was recognized by sera from 22 patients with invasive disease but not by sera from 13 patients harboring nonpathogenic strains. Its surface location is supported by its differential extraction in the detergent phase of Triton X-114 and by surface immunofluorescence of live trophozoites. Unlike previously described amebic surface antigens, this 30-kDa antigen is undetectable in axenic strains that were originally isolated from patients with invasive disease but have been adapted to grow without bacteria. Affinity-purified antibody to the 30-kDa antigen did not promote lysis of complement-resistant pathogenic strains. This surface antigen may be diagnostically important in the identification of pathogenic clinical isolates.


Long term results of pneumatic retinopexy.
Rhegmatogenous retinal detachment is a commonly encountered retinal problem where rapid treatment can prevent irreversible vision loss. Pneumatic retinopexy (PR) is a simple, minimally invasive procedure for retinal reattachment. This study aimed to assess the long-term anatomical and functional outcome of pneumatic retinopexy in primary rhegmatogenous retinal detachment. A prospective interventional study was performed. Subjects with rhegmatogenous retinal detachment who underwent pneumatic retinopexy from May 2006 to May 2007 at Menoufiya University Hospital were included in this study with at least 3 years follow-up. A total of 40 cases were included in the study. The mean age of patients was 44.25 ± 10.85 years. Reattachment of the retina was achieved in 100% of cases. In 75% of cases, the primary intervention was successful. However, the retina redetached in 20% of these during the first 6 months, requiring reinjection or another procedure. Three years after the first intervention, follow-up measurement of the mean visual acuity of the eyes without reoperation was 0.40 ± 0.21 while the mean visual acuity of the eyes which needed additional operations was 0.22 ± 0.13. Sixty percent of the cases obtained long-term retinal reattachment with a single operation success (SOS), with good visual recovery and less morbidity than other more invasive procedures like scleral buckling or pars plana vitrectomy, translating to higher productivity for the patient. This procedure, being quicker than the alternatives, also saves the surgeon's time, making PR a good choice for managing primary rhegmatogenous retinal detachment in developing countries.


Alteration of proteoglycan synthesis in human lung fibroblasts induced by interleukin-1beta and tumor necrosis factor-alpha.
Important constituents of extracellular matrix are collagen, fibronectin, hyaluronan, and various types of proteoglycans, such as versican, perlecan, decorin, and biglycan. Remodeling of extracellular matrix occurs continuously and is affected by various cytokines. The aim of this study was to investigate how interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), separately and in combination, alter fibroblast proliferation, as well as the production of extracellular matrix molecules produced by human fibroblasts from lung. Fibroblast proliferation was inhibited significantly by all treatments, by 12% with IL-1beta and by 16% with TNF-alpha. The combination of IL-1beta and TNF-alpha increased the inhibition further, by 27%. Hyaluronan production was increased by all treatments: 1.7-fold by IL-1beta and 1.5-fold by TNF-alpha. The combination of the two gave a further increase (2.5-fold). Similarly, the production of total proteoglycans was increased. The small proteoglycans, decorin, and biglycan, were regulated differently. Decorin production was inhibited by about 34% by all treatments, while biglycan was upregulated 1.3-fold by TNF-alpha. Versican was upregulated by IL-1beta (1.7-fold), whereas TNF-alpha was without effect. Perlecan was mostly unaffected. The changes in protein production of the various proteoglycans were due to increased transcription, as mRNA levels were also changed to the same extent. Synthesis of mRNA for collagen type I was inhibited by up to 75% with the IL-1beta/TNF-alpha combination. The separate cytokines also decreased the level of collagen type I mRNA, but to a lesser extent: 60% with IL-1beta and 40% with TNF-alpha. In summary, our study indicates that these proinflammatory cytokines affect the regulation of extracellular matrix production, which is of importance for the inflammatory process.


[Determination of isoxanthopterin in human urine by solid phase extraction-high performance anion-exchange chromatography coupled with integrated pulsed amperometric detection].
A sensitive, selective and environmental friendly method for the determination of isoxanthopterin in human urine by solid phase extraction (SPE)-high performance anion exchange chromatography (HPAEC) with integrated pulsed amperometric detector has been developed. The tandem solid phase extraction was employed to purify isoxanthopterin from human urine. The separation of isoxanthopterin was carried out on an IonPac AS21 anion-exchange column with eluent of 0.025 mol/L NaOH at the flow rate of 0.40 mL/min. Under the optimized conditions, the detection limit for isoxanthopterin was 0.003 mg/L, and the linear range was 0.005-0.200 mg/L. The spiked recoveries ranging from 95.4% to 96.8% were obtained in the urine samples from healthy persons and cancer patients, and the relative standard deviation (RSD) was less than 5%. The present method was successfully applied to the determination of isoxanthopterin in urine from healthy individuals and cancer patients.


Diagnosis of paraesophageal omental hiatal hernia by magnetic resonance imaging.
We present a case of an enlarging retrocardiac mass lesion in which we observed the magnetic resonance imaging (MRI) finding of a fatty tumor with contiguous blood vessels extending from the abdominal portion into the thoracic portion of the tumor. These surgically verified findings provide an MRI indication of the presence of a paraesophageal omental hiatal hernia.


Brain activity preceding a 2D manual catching task.
We investigated the event-related desynchronization (ERD) and synchronization (ERS) properties of cortical EEG rhythms in regions of interest (ROI) during the preparation of a 2D task for manual catching of a moving object. EEG signals were recorded through a 32-channel system in eleven healthy subjects during the interception task consisting of 2D catching with the right hand of a handle moving at constant velocity (1.5 m/s) on a predefined straight trajectory. The first session of catching movements (CATCHING_PRE) was compared with a second session after 1 h with identical characteristics (CATCHING_POST) and with other two conditions, where the subjects had to reach and grasp the handle fixed in the medium of platform (REACHING) and they looked at the object moving without catching it (GAZE TRACKING). Changes of cortical rhythms were correlated with dynamic and kinematic indexes of motor performance in both catching sessions. Movements requiring different strategies (predictive versus prospective) are supported by specific changes of cortical EEG rhythms: in the CATCHING condition a more evident power decrease (ERD) in alpha 2 and beta band in the sensorimotor region contralateral to the catching hand was observed, while in the REACHING one a bilateral ERD in beta band was found. Motor learning and movement automatization were characterized by a significant reduction of theta ERS in the anterior cingulate cortex (ACC), a ROI linked to focused attention, and with a shift of neuronal activation in alpha 2 band from the bilateral superior parietal areas to the homologous area of the left hemisphere. Finally, our EEG findings are consistent with the role of supplementary motor (SMA), premotor and prefrontal areas in motor planning and preparation. In particular, theta ERS in left SMA significantly correlated with an improvement of motor performance, as evidenced by its correlation with the training-related reduction of interception time (IT).


Migration trends in British rural areas from the 18th to the 20th centuries.
"Longitudinal residential histories are used to examine the extent to which three rural areas in Britain had distinctive migration histories from the 18th to the 20th centuries. Migration flows into and out of the regions are used to examine the extent to which the regions were integrated into the British migration system, and the relative importance of rural to urban migration is assessed.... Analysis reveals a high degree of short-distance mobility within regions and emphasises the dominance of London in longer-distance migration.... It is also suggested that the role of towns in the migration system has previously been overemphasised, with much migration taking place between small settlements and some movement from large cities to smaller towns and villages.... The analysis challenges some accepted notions about migration in the past, and contributes to the debate about the extent to which British regions became part of a national economic and social system from the 18th century."


Weight gain over 3 kg is associated with worse metabolic syndrome indicators, regardless of weight gain recognition in Japanese workers.
We examined the relationship between recognition of a 3-kg weight gain in 1 year with metabolic syndrome parameters and lifestyle status related to metabolic syndrome or cardiovascular disease in Japanese workers. Data were collected twice between April 2009 and March 2011, and self-reported questionnaires were completed at a follow-up by 275 workers who gained more than 3 kg in 1 year. This study showed that ~40 per cent of those who gained more than 3 kg in a year did not recognise their weight gain, and a weight gain over 3 kg was associated with worse metabolic syndrome parameters regardless of weight gain recognition.


Risk factors for acute ischemic stroke following intravenous thrombolysis: a 2-center retrospective cohort study.
The risk factors associated with in-hospital poor neurological function after intravenous thrombolysis in patients with acute ischemic stroke (AIS) is of major public health interest. The aim of the present study was to screen for risk factors associated with in-hospital poor neurological function after intravenous thrombolysis in patients with acute AIS. This was a population-based cohort study. A total of 878 AIS patients who were admitted to advanced stroke centers of 2 Grade A tertiary hospitals in China between January 2018 and January 2020, and who had undergone intravenous thrombolysis therapy, were included in the present study. Baseline and treatment data of participant were collected. Poor neurological function was defined as National Institutes of Health Stroke Scale (NIHSS) score ≥16 on day 7 after onset, indicating stroke severity. Univariable and multivariable analyses were used to screen out factors associated with the endpoint. After multivariable analysis, risk factors, such as age [odds ratio (OR): 1.099, 95% confidence interval (95% CI): 1.052-1.194, P<0.001], NIHSS2 (NIHSS score immediately after thrombolysis, OR: 1.286, 95% CI: 1.201-1.377, P<0.001), total cholesterol (CHOL; OR: 1.614, 95% CI: 1.036-2.514, p<0.05), urea nitrogen (UREA; OR: 1.205, 95% CI: 1.045-1.390, P<0.05), computed tomography 24 h after thrombolysis (CT2; OR: 6.153, 95% CI: 2.696-14.045, P<0.001), and lower limb deep venous thrombosis (LDVT; OR: 4.398, 95% CI: 1.560-12.398, P<0.05) were found to be associated with poor neurological function. Lipid regulation (OR: 0.065, 95% CI: 0.02-0.215, P<0.001) and high-density lipoprotein cholesterol (HDL-C; OR: 0.038, 95% CI: 0.007-0.202, P<0.001), were found to be protective factors to avoid poor neurological function. Age, NIHSS2, CHOL, UREA, CT2, and LDVT were found to be risk factors of poor neurological function after thrombolysis for AIS. Lipid regulation and HDL-C were found to be protective factors of poor neurological function.


[Investigating the "social brain" through Williams syndrome].
Recent advances in social cognitive neuroscience have led to the concept of the "social brain". The social brain includes neural processes specialized for processing social information necessary for the recognition of self and others, and interpersonal relationships. Because of its unique behavioral phenotypic features which includes 'hypersociability', Williams syndrome has gained popularity among social cognitive neuroscientists. Individuals with Williams syndrome share the same genetic risk factor for cognitive-behavioral dysfunction utilizing brain imaging to elucidate endophenotype provides us with an unprecendented opportunity to study gene, brain and behavior relationships especially those related to social cognition. In this review, we provide an overview of neuroimaging studies on social cognition in Williams syndrome and discuss the neural basis of the social brain.


Resting sympathetic outflow does not predict the morning blood pressure surge in hypertension.
The blood pressure (BP) rise on awakening (morning surge) might be a predictor of hypertension-related cardiovascular complications. Previous studies suggest that the autonomic nervous system may contribute to the early morning BP increase. We tested the hypothesis that resting sympathetic outflow [assessed by direct measures of intraneural sympathetic nerve activity (SNA)] may help predict the morning BP surge in hypertension. We measured muscle SNA (MSNA), heart rate (HR) and BP during undisturbed supine rest in 68 newly diagnosed untreated hypertensive patients (53 men and 15 women, age 40 ± 3 years, BMI 27 ± 1 kg/m(2), mean ± SEM). The morning BP surge was defined as the difference between the morning BP and the pre-awake BP. SBP averaged 143 ± 3 mmHg for daytime and 126 ± 2 mmHg for night-time. Mean HR was 81 ± 2 beats/min for daytime and 69 ± 2 beats/min for night-time. Average MSNA was 32 ± 2 bursts/min., SBP morning surge 19 ± 2 mmHg and HR morning surge 14 ± 2 beats/min. In univariate analysis, MSNA correlated with daytime SBP (r = 0.28, P = 0.02); night-time SBP (r = 0.26, P = 0.03); daytime HR (r = 0.28, P = 0.02); and night-time HR (r = 0.26, P = 0.03). Multivariate analysis, taking into consideration age, BMI and sex, revealed that MSNA was independently related to both daytime (P = 0.006) and night-time HR (P = 0.02), but not to ambulatory SBP. The morning surge of SBP and HR was not related to MSNA (r = 0.01 and r = 0.07, respectively, P = NS). In patients with essential hypertension, MSNA is related to both daytime and night-time HR, but not to the morning BP surge.


Metformin attenuates hyperlipidaemia-associated vascular calcification through anti-ferroptotic effects.
Ferroptosis is a form of regulated cell death that involves metabolic dysfunction resulting from iron-dependent excessive lipid peroxidation. Elevated plasma levels of free fatty acids are tightly associated with cardiometabolic risk factors in patients with obesity, diabetes mellitus, and metabolic syndrome. Metformin (Met) is an antidiabetic drug with beneficial cardiovascular disease effects. The aim of this study was to determine the effects of Met on ferroptosis induced by lipid overload and the effects of these changes on vascular smooth muscle cells (VSMCs) calcification. We developed a hyperlipidaemia-related vascular calcification in vivo model with rats fed a high-fat diet combined with vitamin D3 plus nicotine, and palmitic acid (PA), the most abundant long-chain saturated fatty acid in plasma, was used to induce lipid overload and develop an oxidative stress-related calcification model in vitro. The results showed that Met inhibits hyperlipidaemia-associated calcium deposition in the rat aortic tissue. In vitro, treatment of VSMCs with PA stimulates ferroptosis concomitant with increased calcium deposition in VSMCs, while pretreatment with Met attenuates these effects. Furthermore, PA also promotes the protein expression of the extracellular matrix protein periostin (POSTN) and its secretion into the extracellular environment. More importantly, upregulation of POSTN increased the sensitivity of cells to ferroptosis. Mechanistically, upregulation of POSTN suppresses SLC7A11 expression through the inhibition of p53 in VSMCs, which contributes to a decrease in glutathione synthesis and therefore triggers ferroptosis. Interestingly, overexpression of p53 attenuates the inhibitory effect of POSTN on SLC7A11 expression, accompanied by increased Gpx4 expression. Furthermore, p53 knockdown suppresses Met-mediated anti-ferroptosis effects in PA-treated VSMCs, which may be related to the downregulation of SLC7A11 expression. In addition, supplementation of VSMCs with Met enhances the antioxidative capacity of VSMCs through Nrf2 signalling activation. Collectively, targeting POSTN in VSMCs may provide a new strategy for vascular calcification prevention or treatment.


Augmentation of cellular immune responses to bovine herpesvirus-1 glycoprotein D by vaccination with CpG-enhanced plasmid vectors.
The potential of CpG-enhanced plasmid DNA vectors encoding a truncated secreted form of bovine herpesvirus-1 (BHV-1) glycoprotein D (tgD) to induce enhanced immune responses in cattle was investigated. We created tgD expression plasmids containing 0, 40 or 88 copies of the hexamer 5' GTCGTT 3', a known pan-activating CpG motif in several species. The total tgD-specific IgG titre of calves immunized with these plasmids did not correlate with the CpG content of the plasmid backbone. However, the pBISIA88-tgD-vaccinated group showed a significantly lower IgG1:IgG2 ratio than calves immunized with pBISIA40-tgD or pMASIA-tgD, which has no CpG motifs inserted. Antigen-specific lymphocyte proliferation and IFN-gamma secretion by peripheral blood mononuclear cells correlated positively with the CpG content of the vectors. In contrast, calves that received a killed BHV-1 vaccine had an IgG1-predominant isotype and low lymphocyte proliferation and IFN-gamma levels. Following challenge, the pBISIA88-tgD-immunized group developed the greatest anamnestic response, the highest BHV-1 neutralization titres in serum and a significantly lower level of virus shedding than the saline control group. However, there were no significant differences in clinical symptoms of infection between the DNA-immunized groups and the saline control group. These data indicate that CpG-enhanced plasmids induce augmented immune responses and could be used to vaccinate against pathogens requiring a strong cellular response for protection.


Self-Assembly of Temperature Sensitive Unilamellar Vesicles by a Blend of Block Copolymers in Aqueous Solution.
A self-assembled unilamellar vesicle, which can be used as a drug delivery system, was easily and simply fabricated using a blended system of Pluronic block copolymers. Controlling the hydrophilic mass fraction of block copolymers (by blending the block copolymer with a different hydrophilic mass fraction) and temperature (i.e., the hydrophobic interaction is controlled), a vesicular structure was formed. Small angle neutron scattering measurements showed that the vesicular structure had diameters of empty cores from 13.6 nm to 79.6 nm, and thicknesses of the bilayers from 2.2 nm to 8.7 nm when the hydrophobic interaction was changed. Therefore, considering that the temperature of the vesicle formation is controllable by the concentration of the blended block copolymers, it is possible for them to be applied in a wide range of potential applications, for example, as nanoreactors and nanovehicles.


[Diagnosis of cerebrovascular disorders using nuclear magnetic resonance tomography].
Regarding cerebrovascular diseases magnetic resonance imaging (MRI) provides informations which could not be obtained before by any other imaging method. MRI permits an early detection of ischemic infarctions, exact delineation of lesions near to skull base, and microangiopathy. Further diagnosis of arteriovenous malformations and venous thromboses can be done without using contrast media. Exclusion of acute hemorrhage or subarachnoidal hemorrhage is still a domain of computed tomography (CT). Other MR methods, like magnetic resonance angiography (MRA) and magnetic resonance spectroscopy (MRS) are expected to replace angiography and positron emission tomography (PET) in the near future, at least for some purposes.


DNA Mismatch Repair Deficiency Promotes Genomic Instability in a Subset of Papillary Thyroid Cancers.
Efficient DNA damage repair by MutL-homolog DNA mismatch repair (MMR) enzymes, MLH1, MLH3, PMS1 and PMS2, are required to maintain thyrocyte genomic integrity. We hypothesized that persistent oxidative stress and consequent transcriptional dysregulation observed in thyroid follicles will lead to MMR deficiency and potentiate papillary thyroid tumorigenesis. MMR gene expression was analyzed by targeted microarray in 18 papillary thyroid cancer (PTC), 9 paracarcinoma normal thyroid (PCNT) and 10 normal thyroid (NT) samples. The findings were validated by qRT-PCR, and in follicular thyroid cancers (FTC) and follicular thyroid adenomas (FTA) for comparison. FOXO transcription factor expression was also analyzed. Protein expression was assessed by immunohistochemistry. Genomic integrity was evaluated by whole-exome sequencing-derived read-depth analysis and Mann-Whitney U test. Clinical correlations were assessed using Fisher's exact and t tests. Microarray and qRT-PCR revealed reduced expression of all four MMR genes in PTC compared with PCNT and of PMS2 compared with NT. FTC and FTA showed upregulation in MLH1, MLH3 and PMS2. PMS2 protein expression correlated with the mRNA expression pattern. FOXO1 showed lower expression in PMS2-deficient PTCs (log2-fold change -1.72 vs. -0.55, U = 11, p < 0.05 two-tailed). Rate of LOH, a measure of genomic instability, was higher in PMS2-deficient PTCs (median 3 and 1, respectively; U = 26, p < 0.05 two-tailed). No correlation was noted between MMR deficiency and clinical characteristics. MMR deficiency, potentially promoted by FOXO1 suppression, may explain the etiology for PTC development in some patients. FTC and FTA retain MMR activity and are likely caused by a different tumorigenic pathway.


A ration of care, a measure of doubt.
With limited dollars and skyrocketing costs, Medicaid programs around the country are feeling the squeeze. While some hope to guarantee basic health services by withholding access to certain high-ticket procedures, the question remains: Should we deny any level of care to the poor?


Suction loss during femtosecond laser incision for penetrating keratoplasty.
We present a case of suction loss during a femtosecond laser incision for penetrating keratoplasty in the host cornea. This case illustrates a technique for completing the procedure with no further complications.


Clinical and morphological outcomes after percutaneous needle fasciotomy in Dupuytren's disease according to the contracture severity.
Dupuytren's disease (DD) is a chronic progressive disorder causing contractures in the palmar and digital fascia. The primary aim of management is to correct the deformity while reducing the risk of recurrence and avoiding complications. The purpose of our retrospective study was to validate the efficacity, safety and the rate of recurrence of DD after percutaneous needle fasciotomy (PNF). We present results for a population of 40 patients, divided into three groups, based on the severity of the contracture according to Tubiana staging. We analyzed patient demographic data, encountered complications and the degree of release achieved both post-procedure and at one-year follow-ups. From a total of 98 joints we treated, we obtained satisfactory release [passive extension deficit (PED) ≤10°] in 85% of joints, while full release was obtained in 70% of joints. Full release was obtained mostly in metacarpophalangeal (MCP) joint (95%) rather than proximal interphalangeal (PIP) joint (50%) or distal interphalangeal (DIP) joint (60%). Our patient preferred PNF in comparison to open fasciectomy because of its minimum invasive approach and the quick recovery time. The study shows that PNF has great short-term results and it is suitable for patients who prefer minimally invasive care.


Making the Case: The Use of Lean Six Sigma Methodologies to Improve Staffing in an Acute Hemodialysis Department.
Making a business case to match staffing-to-patient care needs sometimes requires new approaches. Partnering with departments outside of nursing proved successful in one acute hemodialysis department. Working with Lean Six Sigma teammates to define our workflow processes and utilizing the resulting data led to developing a business case, which gained the department 2.5 additional full-time equivalent registered nurses. A staffing template was created to evaluate ongoing patient volumes against current staffing. This staffing template can be used by any hemodialysis unit to aid in determining ongoing staffing requirements.


Pseudo-T2 mapping for normalization of T2-weighted prostate MRI.
Signal intensity normalization is necessary to reduce heterogeneity in T2-weighted (T2W) magnetic resonance imaging (MRI) for quantitative analysis of multicenter data. AutoRef is an automated dual-reference tissue normalization method that normalizes transversal prostate T2W MRI by creating a pseudo-T2 map. The aim of this study was to evaluate the accuracy of pseudo-T2s and multicenter standardization performance for AutoRef with three pairs of reference tissues: fat/muscle (AutoRefF), femoral head/muscle (AutoRefFH) and pelvic bone/muscle (AutoRefPB). T2s measured by multi-echo spin echo (MESE) were compared to AutoRef pseudo-T2s in the whole prostate (WP) and zones (PZ and TZ/CZ/AFS) for seven asymptomatic volunteers with a paired Wilcoxon signed-rank test. AutoRef normalization was assessed on T2W images from a multicenter evaluation set of 1186 prostate cancer patients. Performance was measured by inter-patient histogram intersections of voxel intensities in the WP before and after normalization in a selected subset of 80 cases. AutoRefFH pseudo-T2s best approached MESE T2s in the volunteer study, with no significant difference shown (WP: p = 0.30, TZ/CZ/AFS: p = 0.22, PZ: p = 0.69). All three AutoRef versions increased inter-patient histogram intersections in the multicenter dataset, with median histogram intersections of 0.505 (original data), 0.738 (AutoRefFH), 0.739 (AutoRefF) and 0.726 (AutoRefPB). All AutoRef versions reduced variation in the multicenter data. AutoRefFH pseudo-T2s were closest to experimentally measured T2s.


Diversification of a thieno[2,3-d]pyrimidin-4-one scaffold via regioselective alkylation reactions.
The 2-aryl-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-ones and 2-aryl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-ones have been diversified by alkylation reactions, applying benzylchlorides and N-substituted 2-chloroacetamides as alkylating agents. Under the found uniform conditions the substitution direction does not depend on the structure of the alkylating agent and gives monoalkylated products in high yields with simple workup. The alkylation of the 2,3-dihydropyrimidin-4(1H)-one derivatives proceeds onto the N1-position; however, in the case of pyrimidin-4(3H)-ones the O-alkylated products are formed selectively. An alternative strategy for the synthesis of the N1-benzyl-2,3-dihydropyrimidin-4(1H)-one derivatives is also developed. It applies the redaction of N2-substituted Gewald's amides with aromatic aldehydes and allows simple introduction of various substituents in the final molecule.


Protein interaction with ice.
Many organisms have evolved novel mechanisms to minimize freezing injury due to extracellular ice formation. This article reviews our present knowledge on the structure and mode of action of two types of proteins capable of ice interaction. The antifreeze proteins inhibit ice crystal formation and alter ice growth habits. The ice nucleation proteins, on the other hand, provide a proper template to stimulate ice growth. The potential applications of these proteins in different industries are discussed.


A device for the implantation of multiple cellular deposits into a large volume of brain from a single cannula site.
Current grafting techniques for the treatment of Parkinson's disease incompletely restore the dopaminergic innervation of the caudate/putamen and while, in successful cases, bradykinesia and rigidity are reduced, tremor is largely unaffected. Increasing the number of cellular deposits would allow grafted neurons to be dispersed more widely within the host brain. This might be expected to lead to a more complete reinnervation of the caudate/putamen and therefore a better clinical result. In order to increase the volume of brain accessible to reinnervation without increasing the number of needle passages through the cortex, we have designed a device which allows a Teflon tube to be extruded sideways from the end of a stainless steel cannula. Through this tube, cells can be implanted at some distance in any radial direction from the axis of the cannula. Using such a device we have made up to 12 deposits of lac-z-labeled cells via a single cannula entry into the rat brain, at distances of up to 5 mm from the axis of the cannula. We propose that a similar device could be used to graft embryonic neurons into the human brain.


Pfizer-BioNTech and Sinopharm: A Comparative Study on Post-Vaccination Antibody Titers.
COVID-19 (coronavirus disease 2019) vaccines induce immunity through different mechanisms. The aim of this study is to compare the titers of specific antibodies in subjects vaccinated with either the Pfizer-BioNTech COVID-19 vaccine or the Sinopharm vaccine. This prospective observational cohort included Jordanian adults vaccinated with two doses, 21 days apart, of either of the two aforementioned vaccines. Titers were collected 6 weeks after the administration of the second dose. Overall, 288 participants were included, of which 141 were administered the Pfizer-BioNTech vaccine, while 147 were administered the Sinopharm vaccine. Remarkably, 140 (99.3%) of the Pfizer-BioNTech vaccine recipients had positive IgG titers, while 126 (85.7%) of Sinopharm recipients had positive IgG (p < 0.001). The mean titer for IgG among Pfizer-BioNTech recipients was 515.5 ± 1143.5 BAU/mL, compared to 170.0 ± 230.0 BAU/mL among Sinopharm subjects (p < 0.001). Multivariable regression analysis showed that the Pfizer-BioNTech vaccine positively correlated with positive IgG titers (OR: 25.25; 95% CI: 3.25-196.15; p = 0.002), compared with a negative effect of cardiovascular diseases (OR: 0.33; 95% CI: 0.11-0.99; p = 0.48) on IgG titers. In conclusion, fully vaccinated recipients of the Pfizer-BioNTech vaccine had superior quantitative efficiency compared to Sinopharm recipients. A booster dose is supported for Sinopharm recipients, or those with chronic immunosuppressive diseases.


Social Behavior of Antibiotic Resistant Mutants Within Pseudomonas aeruginosa Biofilm Communities.
The complex spatial structure and the heterogeneity within biofilms lead to the emergence of specific social behaviors. However, the impact of resistant mutants within bacterial communities is still mostly unknown. Thus, we determined whether antibiotic resistant mutants display selfish or altruistic behaviors in mixed Pseudomonas aeruginosa biofilms exposed to antibiotics. ECFP-tagged P. aeruginosa strain PAO1 and its EYFP-tagged derivatives hyperproducing the β-lactamase AmpC or the efflux pump MexAB-OprM were used to develop single or mixed biofilms. Mature biofilms were challenged with different concentrations of β-lactams to monitor biofilm structural dynamics, using confocal laser scanning microscopy (CLSM), and population dynamics, through enumeration of viable cells. While exposure of single wild-type PAO1 biofilms to β-lactams lead to a major reduction in bacterial load, it had little effect on biofilms formed by the resistant mutants. However, the most reveling finding was that bacterial load of wild-type PAO1 was significantly increased when growing in mixed biofilms compared to single biofilms. In agreement with CFU enumeration data, CLSM images revealed the amplification of the resistant mutants and their protection of susceptible populations. These findings show that mutants expressing diverse resistance mechanisms, including β-lactamases, but also, as evidenced for the first time, efflux pumps, protect the whole biofilm community, preserving susceptible populations from the effect of antibiotics. Thus, these results are a step forward to understanding antibiotic resistance dynamics in biofilms, as well as the population biology of bacterial pathogens in chronic infections, where the coexistence of susceptible and resistant variants is a hallmark.


Termination points of the facial artery-A meta-analysis.
The facial artery (FA) is the main artery supplying the anterior face, making this artery a very important structure to consider while performing plastic and reconstructive procedures. The literature shows discrepancies in anatomical classifications and the frequency of occurrence of individual variations. Therefore, the goal of this meta-analysis is to provide surgeons with helpful knowledge about the variety of the termination of FA. Articles with data about the termination of the FA were found in major online medical databases such as PubMed, Scopus, Embase, Web Of Science, and Cochrane Library. A total of 1346 articles were initially evaluated by two independent reviewers. Out of those, 24 articles matched the required criteria, and were used in this meta-analysis. A total of 2119 studied FAs were included in this study. The FA termination patterns were divided into five previously classified types. The data show that the FA terminates most frequently as the lateral nasal or angular artery with the prevalence for this group being 69.81% (95% confidence interval [CI]: 59.83%-78.94%). Authors believe that this is the most accurate and up to date study regarding termination patterns and the prevalence of the FA. The results of this meta-analysis could provide a helpful tool for surgeons preforming plastic and cosmetic procedures, especially when injecting dermal fillers or choosing and preforming facial flaps. Detailed anatomical knowledge about the FA may prevent potential surgical complications.


Midazolam enhances anterograde but not retrograde amnesia in pediatric patients.
Midazolam sedation has been shown to diminish recall of one to four cards shown prior to induction of general anesthesia in pediatric patients. This promising but limited finding prompted us to investigate the effect of midazolam sedation on retrograde and anterograde recall and recognition in children scheduled for elective surgery. Forty patients aged 4-10 yr were randomized using a double-blind study design to receive either 0.2 mg/kg intranasal midazolam or 0.2 ml/5 kg placebo (distilled water) using a Devilbiss #286 atomizer. To assess postoperative memory of preoperative events, recall and recognition tasks were performed using a series of picture cards designed for this purpose. Retrograde amnesia was measured by postoperative recall and recognition of cards shown prior to midazolam/placebo administration, and anterograde amnesia was measured by postoperative recall and recognition of cards shown during the interval between midazolam/placebo administration and induction of general anesthesia. Compared to placebo, the midazolam group experienced a significant postoperative reduction in ability to both recall (P < .003) and recognize (P < .001) cards shown subsequent to midazolam/placebo administration (anterograde amnesia). In distinction, there was no difference between groups in postoperative ability to recall or recognize cards shown prior to midazolam/placebo administration (retrograde amnesia). These results support and extend the inference that midazolam diminishes anterograde recall. In addition, our findings indicate that midazolam diminishes anterograde recognition, thereby providing partial anterograde amnesia without affecting retrograde memory in pediatric patients.


Progress in the analysis of membrane protein structure and function.
Structural information on membrane proteins is sparse, yet they represent an important class of proteins that is encoded by about 30% of all genes. Progress has primarily been achieved with bacterial proteins, but efforts to solve the structure of eukaryotic membrane proteins are also increasing. Most of the structures currently available have been obtained by exploiting the power of X-ray crystallography. Recent results, however, have demonstrated the accuracy of electron crystallography and the imaging power of the atomic force microscope. These instruments allow membrane proteins to be studied while embedded in the bi-layer, and thus in a functional state. The low signal-to-noise ratio of cryo-electron microscopy is overcome by crystallizing membrane proteins in a two-dimensional protein-lipid membrane, allowing its atomic structure to be determined. In contrast, the high signal-to-noise ratio of atomic force microscopy allows individual protein surfaces to be imaged at sub-nanometer resolution, and their conformational states to be sampled. This review summarizes the steps in membrane protein structure determination and illuminates recent progress.


Quantification of specific mRNA by flatbed scintillation counting of dual-labeled dot blots.
A dual-labeling technique was developed for direct quantification of specific mRNA using a flatbed liquid scintillation counter. This method simultaneously measures cpm of 32P- and 35S-labeled probes bound to RNA dot blots and subtracts counts due to nonspecific background radioactivity bound to the filter. Probes for T-cell receptor and beta-actin (as the internal standard) were hybridized both separately and simultaneously to RNA isolated from five different sources. There was concordance between the radioactivity measured from single- and dual-hybridizations for each combination of 35S- and 32P-labeled probes. This methodology directly quantifies specific mRNA sequences bound to membranes and has potential for measuring gene dosage, without the need for re-probing or densitometric analysis.


Antigen detection ELISAs: pretreatment of serum to reduce interference by specific host antibodies.
The pretreatment of serum to reduce interference by specific host antibodies was investigated as a means of improving the sensitivity of antigen detection ELISAs whilst screening serum samples. Four antigen detection assays based on monoclonal antibodies directed against antigens of the bovine filariid Onchocerca gibsoni were used in this study and, of these, three assays suffered a dramatic drop in sensitivity when detecting male O. gibsoni antigen in the presence of bovine serum as compared with antigen in buffer. A number of methods for pretreating serum to eliminate the problem of antibody interference with antigen detection were attempted, including heat and alkali treatments, detergent treatment of heat treated samples and the use of a reducing agent. The pretreatment of serum by boiling for 5 minutes in the presence of an equal volume of 0.1 M Na2EDTA pH 4.0 and recovery of the supernatant fluid following centrifugation at 16000 g was the most effective method of restoring the sensitivity of each of these three assays whilst screening bovine serum. Pretreatment of serum using this method produced up to a 512-fold increase in sensitivity compared with results obtained in assays with non-treated serum.


Annexin A5 inhibits diffuse large B-cell lymphoma cell invasion and chemoresistance through phosphatidylinositol 3-kinase signaling.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma worldwide. Although patient outcomes have significantly improved to a greater than 40% cure rate by the combinatorial cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, which is widely used, resistance to the CHOP regimen continues to pose a problem in managing or curing DLBCL. While it promotes the malignancy and chemo-resistance in certain types of cancer, Annexin A5 is negatively correlated with those in other cancers, including DLBCL. In the present study, we explored the effects of Annexin A5 on DLBCL cell invasion and chemoresistance to CHOP. Stable overexpression and knockdown of Annexin A5 were performed in Toledo and Pfeiffer human DLBCL cell lines. Overexpression of Annexin A5 in both cell lines significantly decreased cell invasion, matrix metalloproteinase-9 (MMP-9) expression/activity, phosphatidylinositol 3-kinase (PI3K) activity/Akt phosphorylation, and cell survival against CHOP-induced apoptosis. On the other hand, knockdown of Annexin A5 markedly increased cell invasion, MMP-9 expression/activity, PI3K activity/Akt phosphorylation, and CHOP-induced apoptosis in the DLBCL cell lines, which was abolished by selective PI3K inhibitor BKM120. In conclusion, our study provides the first in vitro evidence that Annexin A5 inhibits DLBCL cell invasion, MMP-9 expression/activity, and chemoresistance to CHOP through a PI3K-dependent mechanism; it provides new insight not only into the biological function of Annexin A5, but also into the molecular mechanisms underlying DLBCL progression and chemoresistance.


Primary Health Care in Brasil in the times of COVID-19: changes, challenges and perspectives.
The pandemic of Coronavirus Disease 2019 (COVID-19) has put pressure on countries' health systems. Although attention is mostly directed at the hospital sector, since many critically ill people will need intensive care, Primary Health Care (PHC) has also been disrupted. In Brasil, a universal and free health system has existed since the 1988 Constitution, which re-organized the PHC to attend the population. However, like other countries, the Brazilian health system is being overloaded with the increase in the large number of COVID-19 cases. It is worth reflecting on the changes and challenges in PHC during the COVID-19 pandemic in Brasil.


Suppression of PTEN expression by NF-kappa B prevents apoptosis.
NF-kappa B is a heterodimeric transcription activator consisting of the DNA binding subunit p50 and the transactivation subunit p65/RelA. NF-kappa B prevents cell death caused by tumor necrosis factor (TNF) and other genotoxic insults by directly inducing antiapoptotic target genes. We report here that the tumor suppressor PTEN, which functions as a negative regulator of phosphatidylinositol (PI)-3 kinase/Akt-mediated cell survival pathway, is down regulated by p65 but not by p50. Moreover, a subset of human lung or thyroid cancer cells expressing high levels of endogenous p65 showed decreased expression of PTEN that could be rescued by specific inhibition of the NF-kappa B pathway with I kappa B overexpression as well as with small interfering RNA directed against p65. Importantly, TNF, a potent inducer of NF-kappa B activity, suppressed PTEN gene expression in IKK beta(+/+) cells but not in IKK beta(-/-) cells, which are deficient in the NF-kappa B activation pathway. These findings indicated that NF-kappa B activation was necessary and sufficient for inhibition of PTEN expression. The promoter, RNA, and protein levels of PTEN are down-regulated by NF-kappa B. The mechanism underlying suppression of PTEN expression by NF-kappa B was independent of p65 DNA binding or transcription function and involved sequestration of limiting pools of transcriptional coactivators CBP/p300 by p65. Restoration of PTEN expression inhibited NF-kappa B transcriptional activity and augmented TNF-induced apoptosis, indicating a negative regulatory loop involving PTEN and NF-kappa B. PTEN is, thus, a novel target whose suppression is critical for antiapoptosis by NF-kappa B.


Changes in sodium-22 turnover and total body potassium in two-kidney, one-clip renovascular hypertension.
Changes in sodium-22 turnover and total body potassium (TBK) were studied during acute (within 2 weeks after clipping) and chronic (12-14 weeks after clipping) phases in two-kidney, one-clip (2k, 1c) hypertensive rabbits by using a whole body counter. Sodium-22 injected intravenously was eliminated more rapidly in hypertensive rabbits than in controls. The biological half-life (BHL) of sodium-22 was shorter in hypertensive rabbits during both acute (p less than 0.05) and chronic phases (p less than 0.001). A significant negative correlation was obtained between the BHL of sodium-22 and blood pressure (r = -0.588, p less than 0.05) in hypertensive rabbits. TBK decreased significantly at the chronic phase in hypertensive rabbits (p less than 0.05), while TBK showed no significant change in controls. Serum sodium and potassium did not change during the observation period. Increased plasma aldosterone concentration was observed during the acute phase in hypertensive rabbits. These results suggested that sodium retention was not a major factor in the acute and chronic phases of 2k, 1c hypertension in rabbits and that pressure natriuresis could explain, at least in part, the lack of sodium retention. Furthermore, there appears to be a derangement in the intracellular potassium metabolism which may be associated with the maintenance rather than the development of hypertension.


Cannabis edibles packaging: Communicative objects in a growing market.
Cannabis edibles were legalized for recreational use across Canada in October 2019. The Canadian Cannabis Act requires legally produced edibles to be sold in plain single-color packages with limited branded elements and prominent health warning labels, serving size and nutritional information, and product ingredients including amounts of cannabis compounds. Little research, however, assesses what consumers think of standardized packaging, and how product packaging influences perceptions of cannabis edibles. Eight focus groups with young adults (ages 18-24; n = 57) were conducted in November 2018. Participants were recruited from a Canadian university, and asked to assess sample images of cannabis packaging approved by Health Canada. They then discussed the information they would like to see on packages. Focus group discussions were transcribed and analyzed using a descriptive, qualitative approach following methods of process evaluation and inductive coding. Discussions generally pertained to four main themes: dosage and consumption recommendations; food and nutritional information; concerns for children; and health warning labels. Participants suggested improvements for cannabis packaging, including standardized THC units, non-numerical consumption instructions, and unit-dose packaging. Instead of recommending packaging that deters consumption, participants requested packaging features that promote safe consumption by adults while also protecting children. Findings reveal how packages function as communicative objects that convey meanings about safety and risk, yet these meanings may not resonate with Canadian young adults' perceptions of cannabis as relatively safe. While the packaging regulated for use in Canada may be assumed, due to its plain, standardized format, to communicate "little", we highlight tensions in the meanings of such packaging to young adults-especially around competing ideas related to safety and risk.


Anesthetic management of children with in situ Berlin Heart EXCOR.
Modern mechanical devices can support children with severely impaired cardiac function until a donor heart is found for transplantation or native function recovers. Pediatric heart transplantation offers a good chance of survival with a high quality of life to individuals with limited life expectancy and/or severe limitation to daily activities, but many die on the transplant list or are not listed because of a shortage of donor organs. In recent cohorts, there is better outcome when ventricular assist devices (VADs) rather than extracorporeal membrane oxygenation are used as a 'bridge' to transplantation. Anesthesiologists working in centers where VADs are available may increasingly be asked to provide anesthesia to children with such devices in situ, including procedures outside the cardiac surgical operating room. The Berlin Heart EXCOR device is a VAD system with increasing popularity in pediatric practice and has system components available in sizes suitable even for neonates. Postimplantation considerations include hemodynamics, thromboembolic complications and their prevention by anticoagulation, antimicrobial therapy, and the rehabilitation and mobilization of recipients. VAD-specific emergencies must be recognized and managed appropriately by anesthesiologists looking after Berlin Heart recipients. These include malignant dysrhythmias, sudden loss of VAD output, air or clot embolism, and sudden cyanosis. Provision of anesthesia for patients with an in situ Berlin Heart requires attention to particular considerations in preoperative assessment, induction, maintenance, and postoperative care.


Nerve growth factor induces zif268 gene expression via MAPK-dependent and -independent pathways in PC12D cells.
In this study we examined the contribution of MAPK1 and 2 [also known as extracellular signal-regulated kinases (ERK)-1 and 2] to the induction of zif268 mRNA in PC12D cells by using two methods to block the activation of these kinases. In one set of experiments, we inhibited the activation of MAPK by pretreating cells with PD098059, a specific inhibitor of MEK (MAPKK), the immediate upstream activator of MAPK. In the second set of experiments, we blocked the activation of MAPK by overexpressing N17Ras, a dominant-negative form of Ha-Ras. These two approaches yielded similar results and showed that inhibition of MAPK blocks less than half of the induction of zif268 mRNA by NGF. Much of the residual induction of zif268 mRNA is blocked by low concentrations of wortmannin, an inhibitor of phosphatidylinositol (PI) 3-kinase. Since PI 3-kinase was previously shown to function upstream in epidermal growth factor (EGF)-mediated activation of c-Jun N-terminal kinase (JNK), and JNK is known to phosphorylate and activate transcription factors that regulate the expression of zif268, we investigated the role of JNK in the induction of zif268 mRNA by NGF. Stimulation of PC12D cells with NGF weakly activates JNK, but this activation is enhanced rather than inhibited by pretreatment with wortmannin, suggesting that JNK does not function downstream of PI 3-kinase in the induction of zif268 mRNA. A role for JNK in the induction of the zif268 gene is indicated, however, by the fact that cotransfection of expression vectors encoding JIP-1 or the JNK binding domain of JIP-1, which act as dominant-negative inhibitors of JNK, partially blocks the NGF-mediated induction of a luciferase reporter gene linked to the zif268 promoter. Together, these results suggest that MAPK, PI-3 kinase and JNK each play a role in the induction of zif268 gene expression by NGF in PC12D cells.


[Site-directed mutagenesis in the uracil-repair system. Preparation of mutated forms of human alpha 2 interferon].
The mutant forms of human IFN-alpha 2 gene are obtained by oligonucleotide-directed mutagenesis with the use of uracil-repair system. To intensify the process the procedure of the uracil-containing DNA template preparation is modified. It was determined that when mutagenesis is performed in the uracil-repair system the yield of the process depends on the mutant DNA-strand in vitro synthesis efficiency. It is shown that the stability of the 5'-end primer-template complex and the level of the endogenic primers elongation are the basis factors, that determine induction mutations.


Isoleucine 69 and valine 325 form a specificity pocket in human muscle creatine kinase.
Creatine kinase (CK) catalyzes the reversible phosphorylation of creatine by ATP. From a structural perspective, the enzyme utilizes two flexible loop regions to sequester and position the substrates for catalysis. There has been debate over the specific roles of the flexible loops in substrate specificity and catalysis in CK and other related phosphagen kinases. In CK, two hydrophobic loop residues, I69 and V325, make contacts with the N-methyl group of creatine. In this study, we report the alteration of the substrate specificity of CK through the mutagenesis of V325. The V325 to glutamate mutation results in a more than 100-fold preference for glycocyamine, while mutation of V325 to alanine results in a slight preference of the enzyme for cyclocreatine (1-carboxymethyl-2-iminoimidazolidine). This study enhances our understanding of how the active sites of phosphagen kinases have evolved to recognize their respective substrates and catalyze their reactions.


Increased sensitivity to light-induced melatonin suppression in premenstrual dysphoric disorder.
Increased sensitivity to light-induced melatonin suppression characterizes some, but not all, patients with bipolar illness or seasonal affective disorder. The aim of this study was to test the hypothesis that patients with premenstrual dysphoric disorder (PMDD), categorized as a depressive disorder in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), have altered sensitivity to 200 lux light during mid-follicular (MF) and late-luteal (LL) menstrual cycle phases compared with normal control (NC) women. As an extension of a pilot study in which the authors administered 500 lux to 8 PMDD and 5 NC subjects, in the present study the authors administered 200 lux to 10 PMDD and 13 NC subjects during MF and LL menstrual cycle phases. Subjects were admitted to the General Clinical Research Center (GCRC) in dim light (<50 lux) to dark (during sleep) conditions at 16:00 h where nurses inserted an intravenous catheter at 17:00 h and collected plasma samples for melatonin at 30-min intervals from 18:00 to 10:00 h, including between 00:00 and 01:00 h for baseline values, between 01:30 and 03:00 h during the 200 lux light exposure administered from 01:00 to 03:00 h, and at 03:30 and 04:00 h after the light exposure. Median % melatonin suppression was significantly greater in PMDD (30.8%) versus NC (-0.2%) women (p = .040), and was significantly greater in PMDD in the MF (30.8%) than in the LL (-0.15%) phase (p = .047). Additionally, in the LL (but not the MF) phase, % suppression after 200 lux light was significantly positively correlated with serum estradiol level (p = .007) in PMDD patients, but not in NC subjects (p > .05).


[Incidence of factor VII and C3 in vascular anastomosis].
In order to study pathogenesis of vascular prosthesis healing process the following experiment was designed. 16 dogs underwent implantation of unilateral straight aorto-femoral teflon (PTFE, polytetrafluoroethylene) by-pass. After 6 months all dogs were killed, dissected and vascular prostheses with margin of adjacent aorta and femoral artery were collected for further study. Areas of proximal and distal anastomosis were examined immunohistochemically. Presence of coagulation factor VII, and C3 complement factor were studied. The obtained results were analyzed statistically by means of t-Student test. Factor VII as well C3 were found in areas of both proximal and distal anastomosis. Concentration of all two substances in proximal and distal anastomosis was compared. No statistically valid differences in factor VII concentration in proximal and distal anastomosis were found, whereas amounts of C3 factor as well as degree of extracellular matrix infiltration were markedly higher in distal anastomosis.


Early Evaluation and the Effect of Socioeconomic Factors on Neurodevelopment in Infants with Tetralogy of Fallot.
Neurodevelopmental sequelae are prevalent among patients with congenital heart defects (CHD). In a study of infants and children with repaired tetralogy of Fallot (TOF), we sought to identify those at risk for abnormal neurodevelopment and to test associations between socioeconomic and medical factors with neurodevelopment deficits. Single-center retrospective observational study of patients with repaired TOF that were evaluated at the institution's Cardiac Kids Developmental Follow-up Program (CKDP) between 2012 and 2018. Main outcomes included neurodevelopmental test scores from the Bayley Infant Neurodevelopmental Screener (BINS), Peabody Developmental Motor Scale (PDMS), and Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Mixed effects linear regression and marginal logistic regression models tested relationships between patient characteristics and outcomes. Sub-analyses were conducted to test correlations between initial and later neurodevelopment tests. In total, 49 patients were included, predominantly male (n = 33) and white (n = 28), first evaluated at a median age of 4.5 months. Forty-three percent of patients (n = 16) had deficits in the BINS, the earliest screening test. Several socioeconomic parameters and measures of disease complexity were associated with neurodevelopment, independently of genetic syndrome. Early BINS and PDMS performed in infancy were associated with Bayley-III scores performed after 1 year of age. Early screening identifies TOF patients at risk for abnormal neurodevelopment. Socioeconomic factors and disease complexity are associated with abnormal neurodevelopment and should be taken into account in the risk stratification and follow-up of these patients. Early evaluation with BINS and PDMS is suggested for detection of early deficits.


A prospective study of asymptomatic Chlamydia trachomatis in Barbadian women.
A prospective study to determine the prevalence of asymptomatic female genital tract Chlamydia trachomatis infection was performed on 167 women at the Queen Elizabeth Hospital, Barbados, West Indies and at a private clinic. The ELISA (Microtrak, chlamydia EIA, Syva, CA) method was used to detect Chlamydia trachomatis antigen. Nineteen (11.4% 95% CI 6.5-16.3) women were found positive. The efficacy of a single 1 gram dose of azithromycin given orally to 18 patients was tested after 4 weeks. One patient who was pregnant was given 500 mg erythromycin four times daily orally for 1 week. Only six patients (including the pregnant patient) reported for follow up. All six repeat swabs were negative for C. trachomatis antigen. The prevalence of 11.4% asymptomatic chlamydial infection in endocervical swabs in Barbadian women is in agreement with a previous study which reported a prevalence of 18.4% +/7.8%. Patient compliance was assured, using a single dose of azithromycin. It was found to be as effective as doxycyline and ciprofloxacin as reported by other workers.


Local and systemic hormonal responses in pepper leaves during compatible and incompatible pepper-tobamovirus interactions.
Phytohormone levels and the expression of genes encoding key enzymes participating in hormone biosynthetic pathways were investigated in pepper leaves inoculated with two different tobamoviruses. Obuda pepper virus (ObPV) inoculation led to the development of hypersensitive reaction (incompatible interaction), while Pepper mild mottle virus (PMMoV) inoculation resulted in a systemic, compatible interaction. ObPV-inoculation markedly increased not only the levels of salicylic acid (SA) (73-fold) and jasmonic acid (8-fold) but also those of abscisic acid, indole-3-acetic acid, indole-3-butyric acid, cis-zeatin, cis-zeatin-9-riboside and trans-zeatin-9-riboside in the inoculated pepper leaves 3 days post inoculation. PMMoV infection increased only the contents of gibberellic acid and SA. Hormone contents did not change significantly after ObPV or PMMoV infection in non-infected upper leaves 20 days post inoculation. Concentrations of some brassinosteroids (BRs) and progesterone increased both in ObPV- and PMMoV inoculated leaves. ObPV inoculation markedly induced the expression of three phenylalanine ammonia-lyase (PAL) and a 1-aminocyclopropane-1-carboxylate oxidase (ACO) genes, while that of an isochorismate synthase (ICS) gene was not modified. PMMoV inoculation did not alter the expression of PAL and ICS genes but induced the transcript abundance of ACO although later than ObPV. Pre-treatment of pepper leaves with exogenous 24-epi-brassinolide (24-epi-BR) prior to ObPV-inoculation strongly mitigated the visible symptoms caused by ObPV. In addition, 24-epi-BR pre-treatment markedly altered the level of several hormones in pepper leaves following ObPV-inoculation. These data indicate that ObPV- and PMMoV-inoculations lead to intricate but well harmonized hormonal responses that are largely determined by the incompatible or compatible nature of plant-virus interactions.


Metaphor and psychotherapy.
The authors describe the role of metaphor in the theory and practice of psychotherapy. Metaphors are considered fundamental elements of our worlds of language and concepts and not just figures of speech, poetic devices, parables, or creative ways to make interpretations. Metaphors shape the process of therapy by structuring the therapist's perceptions, stance, and attitude. They also organize the way problems are discussed as well as the solution that are seen as effective. The authors review the literature on metaphor in psychotherapy and explore common psychotherapeutic metaphors such as "psychotherapy is war," "the mind is a brittle object," "the conduit metaphor," and a variety of somatic metaphors. They conclude with a discussion of how metaphors function in the process of psychotherapy.


The role of epidural analgesia and anesthesia in surgical outcomes.
Recent clinical evidence suggests that EAA used in combination with general anesthesia has a beneficial effect on surgical outcome compared with general anesthesia and systemic analgesia. Those complications with clear evidence of a reduced incidence in prospective, randomized studies are shown in Table 2. The benefits are greatest in high-risk patients who receive thoracic epidural blockade with local anesthetic agents. Besides reducing the incidence of certain major complications, the adjunctive use of EAA reduces ICU care, hastens recovery, and has cost savings.


Addressing the heterogeneity of the ischemic stroke phenotype in human genetics research.
Many investigators have approached ischemic stroke as a complex phenotype by dividing the ischemic stroke population into distinct subtypes. The purpose of this study was to review systematically the methods used to subtype ischemic stroke in recent genetic studies. The MEDLINE database was searched for articles pertaining to research on the genetics of human ischemic stroke published from January 2000 through January 2002. Abstracts and full-length reports were then sequentially screened to select articles pertaining to original case-control or cohort studies. The initial search yielded 153 publications. Of 41 relevant articles, ischemic stroke was subtyped in 25 (61%). The most common standard subtyping system was the Cerebrovascular Classification of Diseases III system (9 articles). Of the subtyping systems used, 3 had previously published interrater reliability. The subtyping system was reported to have been prespecified in 1 study. Four articles reported using central adjudication. Two articles reported that the person doing the subtyping was blinded to genotype, and 2 reported that the person doing the genotyping was blinded to the patient's subtype status. When investigators subtyped ischemic stroke, they typically used either nonstandard classification systems or systems of undetermined reliability. Important methodological issues, including blinding and prespecification of the classification system, were rarely reported. Advances in methodology and scientific reporting standards would foster identification of subtype-specific genetic risk factors.


"Shining a LAMP" (Loop-Mediated Isothermal Amplification) on the Molecular Detection of Phytopathogens Phytophthora spp. and Phytophthora cactorum in Strawberry Fields.
Phytopathogenic microorganisms belonging to the genus Phytophthora have been recognized many times as causal agents of diseases that lower the yield of many plants important for agriculture. Meanwhile, Phytophthora cactorum causes crown rot and leather rot of berry fruits, mainly strawberries. However, widely-applied culture-based methods used for the detection of pathogens are time-consuming and often inaccurate. What is more, molecular techniques require costly equipment. Here we show a rapid and effective detection method for the aforementioned targets, deploying a simple molecular biology technique, Loop-Mediated Isothermal Amplification (LAMP). We optimized assays to amplify the translation elongation factor 1-α (EF1a) gene for two targets: Phytophthora spp. And Phytophthora cactorum. We optimized the LAMP on pure strains of the pathogens, isolated from organic plantations of strawberry, and successfully validated the assay on biological material from the environment including soil samples, rhizosphere, shoots and roots of strawberry, and with SYBR Green. Our results demonstrate that a simple and reliable molecular detection method, that requires only a thermoblock and simple DNA isolation kit, can be successfully applied to detect pathogens that are difficult to separate from the field. We anticipate our findings to be a starting point for developing easier and faster modifications of the isothermal detection methods and which can be applied directly in the plantation, in particular with the use of freeze-dried reagents and chemistry, allowing observation of the results with the naked eye.


Mathematical modeling of monolignol biosynthesis in Populus xylem.
Recalcitrance of lignocellulosic biomass to sugar release is a central issue in the production of biofuel as an economically viable energy source. Among all contributing factors, variations in lignin content and its syringyl-guaiacyl monomer composition have been directly linked with the yield of fermentable sugars. While recent advances in genomics and metabolite profiling have significantly broadened our understanding of lignin biosynthesis, its regulation at the pathway level is yet poorly understood. During the past decade, computational and mathematical methods of systems biology have become effective tools for deciphering the structure and regulation of complex metabolic networks. As increasing amounts of data from various organizational levels are being published, the application of these methods to studying lignin biosynthesis appears to be very beneficial for the future development of genetically engineered crops with reduced recalcitrance. Here, we use techniques from flux balance analysis and nonlinear dynamic modeling to construct a mathematical model of monolignol biosynthesis in Populus xylem. Various types of experimental data from the literature are used to identify the statistically most significant parameters and to estimate their values through an ensemble approach. The thus generated ensemble of models yields results that are quantitatively consistent with several transgenic experiments, including two experiments not used in the model construction. Additional model results not only reveal probable substrate saturation at steps leading to the synthesis of sinapyl alcohol, but also suggest that the ratio of syringyl to guaiacyl monomers might not be affected by genetic modulations prior to the reactions involving coniferaldehyde. This latter model prediction is directly supported by data from transgenic experiments. Finally, we demonstrate the applicability of the model in metabolic engineering, where the pathway is to be optimized toward a higher yield of xylose through modification of the relative amounts of the two major monolignols. The results generated by our preliminary model of in vivo lignin biosynthesis are encouraging and demonstrate that mathematical modeling is poised to become an effective and predictive complement to traditional biotechnological and transgenic approaches, not just in microorganisms but also in plants.


An unusual dearomatized adduct formed by reaction of 4'-fluoro-4-(acetylamino)biphenyl N-sulfate with deoxyadenosine.
The sulfate ester of the liver carcinogen N-hydroxy-4'-fluoro-4-(acetylamino)biphenyl (FAABP-N-sulfate) is believed to be a reactive intermediate in the male rat liver in vivo. After reaction of FAABP-N-sulfate with double-stranded calf thymus DNA in vitro, 30% of the adducts was identified as N-(deoxyguanosin-8-yl)-4'-fluoro-4-(acetylamino)biphenyl(dG-C8- FAABP) and 16% was suggested to be 3-(deoxyguanosin-N2-yl)-4'-fluoro-4-(acetylamino)biphenyl. To investigate the identity of the remaining adducts, FAABP-N-sulfate was reacted with deoxyadenosine. Two adducts could be isolated, which were identified by 1H NMR and mass spectrometry as 3-(deoxyadenosin-N6-yl)-4'-fluoro-4-(acetylamino)biphenyl (3-dA-N6-FAABP) and -(deoxyadenosin-N6-yl)-4'-fluoro-4-(acetylimino)-3, 4-dihydrobiphenyl (3-dA-N6-FHAIBP). An additional center of chirality is introduced at C3 (biphenyl) in the latter adduct. Therefore, 3-dA-N6-FHAIPB exists as a pair of two diastereomers with H-3 (biphenyl) in the alpha or beta position. Hydrogen bonding between the proton on N6 (adenine) and the imine nitrogen or the acetylimino oxygen is suggested to stabilize 3-dA-N6-FHAIBP and to prevent its conversion to 3-dA-N6-FAABP by restoration of the aromatic system. The adduct 3-dA-N6-FHAIBP was also formed in the reaction of N-OSO3H-FAABP with DNA; it accounted for 3-6% of total covalent binding.


Homocysteine and vascular access thrombosis in hemodialysis patients.
Vascular access remains the Achilles' heel of successful hemodialysis, and thrombosis is the leading cause of vascular access failure. Hyperhomocystinemia is common in hemodialysis patients and is associated with venous and arterial thrombosis in patients without end-stage renal disease. In the study, 65 hemodialysis patients with native arteriovenous fistula were included. Two groups of patients were defined: group A including 45 patients with their vascular access either never or only once thrombosed, and group B including 20 patients with two or more thromboses of their vascular access. We determined serum concentrations of total homocysteine (immunoassay, Abbott) in our patients. In 63 (96.9%) patients, hyperhomocystinemia was presented. There was no statistically significant difference between group A and B regarding age, gender and duration of hemodialysis treatment. Total homocysteine concentrations were higher in group A (42.1 +/- 18.6 micromol/l) than in group B (36.1 +/- 18.1 micromol/l) patients but the difference was small and not statistically significant. We found no significant differences in total homocysteine concentrations between group A (thrombosis non-prone) and group B (thrombosis prone) patients. Our results suggest that thrombosis of native arteriovenous fistulas may not be caused by hyperhomocystinemia in these patients.


Conformational studies of two histamine H2-receptor antagonistic phenylformamidines: mifentidine and its guanidinothiazole analogue DA 4643.
Two histamine H2-receptor antagonists of the phenylformamidine type, mifentidine (N-isopropyl-N'-(4-1H-imidazol-4-yl-phenyl) formamidine dihydrochloride; I) and DA 4643 (N-methyl-N'-(3-(2-guanidinothiazol-4-yl)-phenyl) formamidine dihydrochloride; II), have been investigated by experimental physico-chemical studies and theoretical conformational analysis. PKa determinations on the two molecules I and II show that these substances exist at physiological pH (7.4) predominantly as their monoprotonated forms at the formamidine moiety. Semiempirical quantum mechanical (MNDO, CNDO/2) and molecular mechanics (MMPI) calculations show a preference of the nearly planar conformations for I and of different low energy rotamers for II. The energy of these conformers is a function of two important torsion angles, one around the bond joining the imidazole, or the guanidinothiazole, and the phenyl ring and the other around the bond joining the phenyl ring and the formamidinium cation. When the distances between crucial parts present in I and II are considered, it results that the relatively higher flexibility of II allows accommodation of amidine pairs present in the latter at a distance similar to that found for correspondent pairs in the conformationally more restricted I. Conformational aspects of I and II are discussed with reference to a recently described conformation of cimetidine determined by X-ray method. A hypothesis of binding of H2-receptor antagonists of the phenylformamidine type is advanced with reference to electrostatic potential maps calculated for crucial part structures of I, II and cimetidine. The present work supports the hypothesis that both mifentidine and DA 4643 interact with the histamine H2-receptor at the same site, utilizing in the binding process the same, or closely similar, receptor structural features.


Pancreaticobiliary manifestations of AIDS.
The pancreas and the biliary tract are frequent sites of infectious, Inflammatory, and neoplastic disease in patients with HIV infection. However, the symptoms of pancreaticobiliary involvement may be relatively mild so that the prevalence of these disorders is probably underestimated. An appreciation of the imaging findings of HIV-associated pancreaticobiliary disorders is important because involvement of these organs may be the only criterion that establishes the diagnosis of AIDS (Table 1).


Genetic architecture of atherosclerosis dissected by QTL analyses in three F2 intercrosses of apolipoprotein E-null mice on C57BL6/J, DBA/2J and 129S6/SvEvTac backgrounds.
Quantitative trait locus (QTL) analyses of intercross populations between widely used mouse inbred strains provide a powerful approach for uncovering genetic factors that influence susceptibility to atherosclerosis. Epistatic interactions are common in complex phenotypes and depend on genetic backgrounds. To dissect genetic architecture of atherosclerosis, we analyzed F2 progeny from a cross between apolipoprotein E-null mice on DBA/2J (DBA-apoE) and C57BL/6J (B6-apoE) genetic backgrounds and compared the results with those from two previous F2 crosses of apolipoprotein E-null mice on 129S6/SvEvTac (129-apoE) and DBA-apoE backgrounds, and B6-apoE and 129-apoE backgrounds. In these round-robin crosses, in which each parental strain was crossed with two others, large-effect QTLs are expected to be detectable at least in two crosses. On the other hand, observation of QTLs in one cross only may indicate epistasis and/or absence of statistical power. For atherosclerosis at the aortic arch, Aath4 on chromosome (Chr)2:66 cM follows the first pattern, with significant QTL peaks in (DBAx129)F2 and (B6xDBA)F2 mice but not in (B6x129)F2 mice. We conclude that genetic variants unique to DBA/2J at Aath4 confer susceptibility to atherosclerosis at the aortic arch. A similar pattern was observed for Aath5 on chr10:35 cM, verifying that the variants unique to DBA/2J at this locus protect against arch plaque development. However, multiple loci, including Aath1 (Chr1:49 cM), and Aath2 (Chr1:70 cM) follow the second type of pattern, showing significant peaks in only one of the three crosses (B6-apoE x 129-apoE). As for atherosclerosis at aortic root, the majority of QTLs, including Ath29 (Chr9:33 cM), Ath44 (Chr1:68 cM) and Ath45 (Chr2:83 cM), was also inconsistent, being significant in only one of the three crosses. Only the QTL on Chr7:37 cM was consistently suggestive in two of the three crosses. Thus QTL analysis of round-robin crosses revealed the genetic architecture of atherosclerosis.


The TRPV1 ion channel antagonist capsazepine inhibits osteoclast and osteoblast differentiation in vitro and ovariectomy induced bone loss in vivo.
The vanilloid type 1 ion channel (TRPV1) is known to play an important role in the regulation of pain and inflammation. Pharmacological ligands of TRPV1 regulate human osteoclast formation in vitro, but the effects of these agents on osteoblast function have not been studied and their effects on bone loss in vivo are unknown. Here we examined the effects of the TRPV1 ion channel antagonist capsazepine on mouse osteoclast and osteoblast differentiation in vitro and ovariectomy induced bone loss in vivo. Capsazepine inhibited osteoclast formation and bone resorption in a dose dependent manner in bone marrow-osteoblast co-cultures and RANKL generated osteoclast cultures, whereas the TRPV1 agonist capsaicin enhanced RANKL and M-CSF stimulated osteoclast formation. Capsazepine also suppressed RANKL induced IkappaB and ERK1/2 phosphorylation and caused apoptosis of mature osteoclasts and also inhibited alkaline phosphatase activity and bone nodule formation in calvarial osteoblast cultures. Studies in vivo showed that capsazepine (1mg/kg/day) inhibited ovariectomy induced bone loss in mice and histomorphometric analysis showed inhibitory effects on indices of bone resorption and bone formation. We conclude that pharmacological blockade of TRPV1 ion channels by capsazepine inhibits osteoclastic bone resorption and protects against ovariectomy induced bone loss in mice, but also inhibits osteoblast activity and bone formation.


Increase in Dry Weight and Total Nitrogen Content in Zea mays and Setaria italica Associated with Nitrogen-fixing Azospirillum spp.
The association between nitrogen-fixing bacteria from the genus Azospirillum and the grasses Zea mays and Setaria italica was investigated in sterilized Leonard-jar assemblies. Nitrogen-fixing bacteria isolated from Cynodon dactylon roots in Israel and Azospirillum brasilense (Sp-7, Sp-80, and Cd) were examined. C(2)H(2) reduction activity was detected in systems containing 0.0 to 0.08 but not in those containing 0.16 gram per liter NH(4)NO(3). The organisms tested significantly increased plant dry weight (50-100%), total N content of leaves (50-100%) and C(2)H(4) production (300-1000 nanomoles C(2)H(4) per plant per hour). Highest C(2)H(2) reduction activities were obtained above 30 C and with high light intensities. Significant increases in S. italica dry weight (DW) and nitrogen (N) content were observed in sand (DW = 80%, N = 150%), sandy loam soil (DW = 80%, N = 75%) and loess (DW = 37%, N = 25%). The results obtained in this work clearly demonstrate the potential benefit of inoculating grasses with Azospirillum.


Is the incidence of dementing illness changing? A 25-year time trend study in Rochester, Minnesota (1960-1984)
We performed a time trend study of incidence of dementing illness in Rochester, Minnesota. We ascertained age- and sex-specific incidence rates for the five quinquennia, 1960 through 1984. The incidence rates sharply increased with advancing age, reaching a high of 2,922/100,000 person years in the group 85 years and older. For dementia caused either solely or predominantly by Alzheimer's disease, this figure was 2,600/100,000 person years for the oldest age group. There were no significant differences in the incidence of dementing illness between men and women. In the oldest age groups in the last two quinquennia of study, there appears to be a trend toward increasing incidence rates. Over the years, the proportion of cases attributed to dementia due to unknown causes has decreased while the proportion of cases attributed to Alzheimer's disease has increased.


Complete mitochondrial genome of cylicocyclus auriculatus: molecular structure and phylogenetic analysis.
Cylicocyclus spp. (Nematoda: Strongylida: Cyathostominae) are the common and important parasitic nematodes found in horses and donkeys worldwide. In this study, the complete mitochondrial genome of Cylicocyclus auriculatus Looss 1900, a representative member of this genus from the donkey in Southwest China was determined using the next-generation DNA sequencing technology. The genome was 13,851 bp in size and consisted of 36 genes including 12 protein-coding genes (atp6, cox1-3, cytb, nad1-6 and nad4L), 22 transfer RNA genes and two ribosomal RNA genes (rrnL and rrnS), as well as two non-coding regions. Phylogenetic analysis showed that C. auriculatus and Cylicocyclus insigne Boulenger 1917 were closely related, and then both grouped with other congeneric species and formed a monophyletic relationship with either species of Cyathostomum, Coronocyclus, Cyathostomum, Cylicostephanus or Cylicodontophorus, demonstrating their phylogenetic stability within Cyathostominae. These cumulative mitochondrial DNA data provide novel and useful genetic markers for molecular diagnostic, systematic and evolutionary biological studies of Cyathostominae nematodes.


Human eggs, zygotes, and embryos express the receptor angiotensin 1-converting enzyme 2 and transmembrane serine protease 2 protein necessary for severe acute respiratory syndrome coronavirus 2 infection.
To study messenger ribonucleic acid (mRNA) and protein expressions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry receptors (angiotensin 1-converting enzyme 2 [ACE2] and CD147) and proteases (transmembrane serine protease 2 [TMPRSS2] and cathepsin L [CTSL]) in human oocytes, embryos, and cumulus (CCs) and granulosa cells (GCs). Research study. Clinical in vitro fertilization (IVF) treatment center. Patients undergoing IVF were treated at the Colorado Center for Reproductive Medicine. Oocytes (germinal vesicle and metaphase II [MII]) and embryos (1-cell [1C] and blastocyst [BL]) were donated for research at the disposition by the patients undergoing IVF. Follicular cells (CC and GC) were collected from women undergoing egg retrieval after ovarian stimulation without an ovulatory trigger for in vitro maturation/IVF treatment cycles. Presence or absence of ACE2, CD147, TMPRSS2, and CTSL mRNAs detected using quantitative reverse transcription polymerase chain reaction and proteins detected using capillary Western blotting in human oocytes, embryos, and ovarian follicular cells. The quantitative reverse transcription polymerase chain reaction analysis revealed high abundance of ACE2 gene transcripts in germinal vesicle and MII oocytes than in CC, GC, and BL. ACE2 protein was present only in the MII oocytes, and 1C and BL embryos, but other ACE2 protein variants were observed in all the samples. TMPRSS2 protein was present in all the samples, whereas mRNA was observed only in the BL stage. All the samples were positive for CD147 and CTSL mRNA expressions. However, CCs and GCs were the only samples that showed coexpression of both CD147 and CTSL proteins in low abundance. CCs and GCs are the least susceptible to SARS-CoV-2 infection because of lack of the required combination of receptors and proteases (ACE2/TMPRSS2 or CD147/CTSL) in high abundance. The coexpression of ACE2 and TMPRSS2 proteins in the MII oocytes, zygotes, and BLs demonstrated that these gametes and embryos have the cellular machinery required and, thus, are potentially susceptible to SARS-CoV-2 infection if exposed to the virus. However, we do not know whether the infection occurs in vivo or in vitro in an assisted reproductive technology setting yet.


Miniature laser powder bed fusion system for in situ synchrotron x-ray micro-computed tomography experiments at the European Synchrotron Radiation Facility.
We describe our miniature laser powder bed fusion (L-PBF) system for in situ synchrotron x-ray micro-computed tomography (XCT) at the European Synchrotron Radiation Facility. This replicator was designed to extend the characterization of L-PBF to 3D. This instrument fills in a technical gap because the existing replicators were mostly designed to shed light on the dynamic mechanisms involved in molten pool formation but, therefore, suffered from a lack of 3D information. Technical details regarding the setup and beamline integration are given. Experimental validations via post-mortem XCT scans and in situ scans acquired during experiments conducted at the BM05 beamline of the European Synchrotron Radiation Facility are provided. Based on a few illustrative examples, we show that such a replicator opens the path to collect key 3D information that to date could not be available. Our miniature instrument complements the other replicators developed in the world by other research groups that enable operando x-ray imaging (radiography) and operando x-ray diffraction.


Effectiveness of a digital dietary intervention program targeting young adults before parenthood: protocol for the PREPARED randomised controlled trial.
The importance of preconception health for lifelong physical and mental health in the next generation has gained increasing recognition in recent years. Preconception paternal and maternal risk factors such as obesity and inadequate diet affect the metabolic and cardiovascular health of their offspring later in life. This highlights the importance of diet and dietary behaviour in the years before parenthood. In our project, PREPARED, we will evaluate the effectiveness of a digital intervention targeting young adults. Our primary aim is to improve participants' preconception diet, and our secondary aim is to improve preconception quality of life and maternal and child perinatal outcomes. We plan to recruit 7000 men and women individually, aged 20-35 years without children, to be randomised to an intervention or a control group. The intervention group will receive access to a digital resource for 6 months promoting a healthy diet for their health now, later in life and for the next generation. Follow-up is up to 20 years or until they have their first child. To evaluate intervention effects, we will collect dietary data (2×24-hour dietary recalls and a screener). For those participants for which birth ensues, we will link study data with data from the Medical Birth Registry of Norway on maternal and child perinatal outcomes. The study is approved by the Regional Ethics Committee, the Norwegian Data Protection Service and our Faculty Ethical Committee (REC: 78104, NSD: 907212, FEC 20/10119). Participation is voluntary and all participants will provide informed consent. Participants can withdraw their consent without giving any reason. Findings will be communicated to the public through a project website and social media, and to professionals through conferences and peer-reviewed papers. ISRCTN44294662.


[Fever and malaria in children under 5 years of age in Benin: do we have accurate statistics?].
In Benin, mothers generally seek health care for their children with fever and malaria only when complications appear, including severe anemia, convulsions, and coma. Statistics from the national health system are based on consultations at national health care centers and do not take into account existing cases in the community. To determine the prevalence of malaria from the analysis of subjects with fever and their management in two participating villages. This evaluation--and a better approach to fighting childhood malaria--rely on habits of management and care-seeking and the extent of parental participation. Parents in two villages were interviewed about their practices in managing fever in children and about active malaria screening. The prevalence of (thick smear-positive) malaria was the same in both villages (p>0.05). Parents brought children to health centers for consultation in only 6% of the cases of fever. Treatment was administered immediately within 48 hours for most children (75%) but only 15% received adequate anti-malarial treatment. Care-seeking is highly associated with perceptions and representations of childhood fever: for every case treated at the health centre, 16 remain in the community. Adequate management of fever and the malaria often associated with it requires understanding the perceptions and representations of parents, which will make it possible to learn the true proportion of malaria in fevers in the two villages and thus to apply appropriate strategies.


[A case of right ventricular rupture due to blunt trauma].
A 33-year-old male was involved in a single motor vehicle accident and was referred to our hospital 135 minutes after injury. He had a sign of cardiac tamponade and immediately pericardial window was performed at the emergency department, but hypotension went worse. We transferred him to the operating room, and a median sternotomy could be done after cardiopulmonary resuscitation. There was a 4 cm tear in the right ventricular outlet and that was repaired primarily. Cardiac rupture due to blunt trauma is highly lethal, and prompt diagnosis is necessary for a favorable outcome. A high index of suspicion, avoidance of unnecessary diagnostic studies, and immediate surgical intervention are critical for successful management.


Your Soul Spills Out: The Creative Act Feels Self-Disclosing.
Breaking from the typical focus on the antecedents of creativity, we investigate the psychological and interpersonal consequences of being creative. Across five experiments, we find that generating creative ideas is revealing of the self and thus prompts the perception of self-disclosure. Individuals respond to the expectation to be creative with greater self-focus-adopting their own idiosyncratic perspective on the task and thinking about their own personal preferences and experiences in connection to the problem. Because creative ideas derived from self-focused attention are uniquely personal, the act of sharing a creative idea is, in turn, perceived to be revealing of the self. Finally, an interactive dyad study shows that sharing creative ideas makes partners more confident in the accuracy of judgments they made about each other's personality. We discuss the implications of our findings for future research investigating the consequences of creativity.


Interaction of the LILRB1 inhibitory receptor with HLA class Ia dimers.
Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) has been reported to interact with a wide spectrum of HLA class I (HLA-I) molecules, albeit with different affinities determined by allelic polymorphisms and conformational features. HLA-G dimerization and the presence of intracellular Cys residues in HLA-B7 have been shown to be critical for their recognition by LILRB1. We hypothesized that dimerization of classical HLA class Ia molecules, previously detected in exosomes, might enhance their interaction with LILRB1. A soluble LILRB1-Fc fusion protein and a sensitive cellular reporter system expressing a LILRB1-ζ chimera were employed to assess receptor interaction with different HLA class Ia molecules transfected in the human lymphoblastoid 721.221 cell line. Under these conditions, intracellular Cys residues and HLA-I dimerization appeared associated with increased LILRB1 recognition. On the other hand, a marginal interaction of LILRB1 with primary monocytic cells, irrespective of their high HLA-I expression, was enhanced by type I interferon (IFN). This effect appeared disproportionate to the cytokine-induced increase of surface HLA-I expression and was accompanied by detection of HLA class Ia dimers. Altogether, the results support that a regulated assembly of these noncanonical HLA-I conformers during the immune response may enhance the avidity of their interaction with LILRB1.


[The seroconversion of Chlamydia abortus in sheep from the region of Vorarlberg before and after Alpine pasturing].
In total, 796 serum samples of sheep on commune alpine pastures in the region of Vorarlberg were investigated by a commercial ELISA kit for antibodies against Chlamydia abortus, the agent of ovine enzootic abortion. The aim of the study was to determine the seroprevalence within this region and to compare these results with the seroprevalence in the neighboring canton Graubünden as well as to obtain data on the seroconversion after alpine pasturing. Therefore, 421 samples were collected before and 375 samples after alpine pasturing, whereas corresponding serum samples were available from 359 sheep. Within the region of Vorarlberg, a mean seroprevalence of 9.2 % was calculated with a threshold of 60 %. Seroconversion for C. abortus occurred in 5.0 % of animals with corresponding serum samples. Seroprevalence values were comparable to Swiss regions with similar management systems, although the neighboring canton Graubünden is known to have a much more higher seroprevalence of 43 %. In conclusion, the traditional animal exchange between these two regions is not significantly favoring the spread of C. abortus.


Treatment philosophy and retreatment rates following piezoelectric lithotripsy.
Second generation lithotriptors offer the advantage of anesthesia-free fragmentation of renal and ureteral calculi but they frequently require multiple treatments to attain a stone-free status. However, excessive single lithotripsy sessions or multiple treatments may be associated with significant damage to the kidney. For some clinicians a common treatment philosophy involves evaluation of serial plain abdominal films every 24 hours after lithotripsy and immediate retreatment of all patients with incomplete fragmentation. To avoid unnecessary retreatments and, thus, minimize potential renal damage, we prospectively evaluated 100 patients undergoing lithotripsy on a Wolf Piezolith 2300 device. Patients were routinely treated with 4,000 shocks at 1,100 bar. Serial plain abdominal films were obtained at 1 day and 2 weeks after lithotripsy. The need for retreatment was determined by the plain abdominal film results. Additional therapy was considered necessary if there was no stone fragmentation or if residual fragments measured greater than 4 mm. Of the patients whose plain abdominal film at 24 hours indicated the need for a repeat treatment 43% were stone-free on the 2-week film. Thus, these patients were spared an unnecessary treatment by allowing adequate time for the stone fragments to pass spontaneously. Our data suggest that repeat treatments on second generation lithotriptors should not be performed within 24 hours. Rather, the patient should be reevaluated at least 1 to 2 weeks later to avoid unnecessary retreatment with the attendant potential for renal injury. In addition, when comparing the retreatment rates of various lithotriptors, one should also consider the treatment philosophy used at the particular institution and the timing of the radiographic studies used to determine the stone-free status.


Stable and inducible arsenite resistance in Chinese hamster cells.
A number of Chinese hamster V79 cell sublines that are arsenite resistant or arsenite sensitive were isolated. After more than 6 months of growth in the absence of arsenite, these sublines still maintain their arsenite-resistant or -sensitive phenotypes. At least some arsenite-resistant cell lines are also cross-resistant to sodium arsenate and potassium antimonyl tartrate. Wild-type or arsenite-resistant sublines show a further increase in resistance to toxic concentrations of arsenite after pretreatment with a nontoxic concentration. Pretreatment of cells with a nontoxic dose of arsenite also increased their survival to toxic doses of antimonite. Likewise, pretreatment with antimonite increased survival to arsenite as well as to antimonite. The inducible arsenite resistance increases with pretreatment time, reaching a plateau after 8 hr of pretreatment. Fusion of arsenite-resistant cells with arsenite-sensitive cells demonstrated a clear dominance of arsenite resistance. These results suggest that mammalian cells contain an arsenite/antimonite pump whose activity may be modulated by prior exposure to arsenite or antimonite.


Soliton dynamics in a PT-symmetric optical lattice with a longitudinal potential barrier.
We present dynamics of spatial solitons propagating through a PT symmetric optical lattice with a longitudinal potential barrier. We find that a spatial soliton evolves a transverse drift motion after transmitting through the lattice barrier. The gain/loss coefficient of the PT symmetric potential barrier plays an essential role on such soliton dynamics. The bending angle of solitons depends on the lattice parameters including the modulation frequency, incident position, potential depth and the barrier length. Besides, solitons tend to gain a certain amount of energy from the barrier, which can also be tuned by barrier parameters.


Internalizing and externalizing dimensions and alcohol use in first time DWI offenders: indirect effects through coping self-efficacy.
Using cross-sectional data and structural equation modeling, we evaluated whether coping self-efficacy to abstain from drinking in various situations accounted for the relationship between internalizing (depression, anxiety) and externalizing (aggression, low socialization) dimensions with problematic alcohol use in 292 first-time DWI offenders. Results indicated that an internalizing dimension indirectly predicted problematic alcohol use through coping self-efficacy in negative situations only, whereas an externalizing dimension indirectly predicted problematic alcohol use through coping self-efficacy in positive situations only. These findings support two potential pathways to problematic drinking behavior among DWI offenders and suggest that internalizing and externalizing dimensions may differentially predict high risk drinking situations due to one's inability to abstain in specific situations.


KPNB1, XPO7 and IPO8 mediate the translocation ofNF-κB/p65 into the nucleus.
NF-κB/p65 is retained in the cytoplasm until it is activated in response to stress. Nuclear import of p65 is regulated by importin α in a nuclear localization signal (NLS)-dependent manner. However, the role of importin β family members in the nuclear translocation of p65 is largely unclear. In this study, using high-content siRNA screening, we identified three of 17 importin β family members that are involved in the nuclear import of p65. Our data showed that knockdown of KPNB1, XPO7 and IPO8 reduced the amount of nuclear p65 following tumor necrosis factor-α (TNF-α) stimulation, resulting in lower NF-κB activity. KPNB1 was the major importin β receptor for p65 import, and this import was dependent on the NLS of p65. However, NLS-mutated p65 still entered the nucleus and bound to XPO7 and IPO8. Interestingly, among the six members of the importin α family, KPNA2 was most important for p65 import. Taken together, our results show that the import of p65 mainly relies on the canonical KPNA2/KPNB1 pathway; however, p65 is also imported by an alternative pathway that is independent of its NLS. Redundant importin receptors are likely to maintain the important function of p65 according to need.