Injury incidence and balance in rugby players.
Objective : This study determined and correlated injury incidence and balance in rugby players. A prospective survey with balance testing was conducted on first year rugby academy players (N= 114). Injury incidence, static and dynamic balance were tested pre and post-season using a Biosway portable balance system. The data was analysed using paired and independent samples t-tests at p<0.05, Odds ratios, and Spearman's correlation coefficients. 75.50% participated, 71.40% were 18 years old, and 71.40% were White. Injury was sustained by 83% of players with the knee (25%) most commonly injured. Injury incidence was 1.52 per player with an injury rate of 5.95 injuries per 1000 match playing hours. The Stability Index increased significantly (p=0.03) by 15% in the medial/lateral direction post-season compared to pre-season. Significant differences in post-test anterior posterior and overall static and front and front right dynamic stability between injured and uninjured players were noted. Risk factors for injury included the scrum-half (14.80%) playing position, injuries in the 2nd half of the match (57%), and during contact (67%). Conclusion : Injury incidence was related to static and dynamic balance in forward right direction only.


Evolutionary dynamics of insertion sequences in relation to the evolutionary histories of the chromosome and symbiotic plasmid genes of Rhizobium etli populations.
Insertion sequences (IS) are mobile genetic elements that are distributed in many prokaryotes. In particular, in the genomes of the symbiotic nitrogen-fixing bacteria collectively known as rhizobia, IS are fairly abundant in plasmids or chromosomal islands that carry the genes needed for symbiosis. Here, we report an analysis of the distribution and genetic conservation of the IS found in the genome of Rhizobium etli CFN42 in a collection of 87 Rhizobium strains belonging to populations with different geographical origins. We used PCR to generate presence/absence profiles of the 39 IS found in R. etli CFN42 and evaluated whether the IS were located in consistent genomic contexts. We found that the IS from the symbiotic plasmid were frequently present in the analyzed strains, whereas the chromosomal IS were observed less frequently. We then examined the evolutionary dynamics of these strains based on a population genetic analysis of two chromosomal housekeeping genes (glyA and dnaB) and three symbiotic sequences (nodC and the two IS elements). Our results indicate that the IS contained within the symbiotic plasmid have a higher degree of genomic context conservation, lower nucleotide diversity and genetic differentiation, and fewer recombination events than the chromosomal housekeeping genes. These results suggest that the R. etli populations diverged recently in Mexico, that the symbiotic plasmid also had a recent origin, and that the IS elements have undergone a process of cyclic infection and expansion.


Head-Mounted Augmented Reality in the Planning of Cerebrovascular Neurosurgical Procedures: A Single-Center Initial Experience.
Augmented reality (AR) technology has played an increasing role in cerebrovascular neurosurgery over the last 2 decades. Hence, we aim to evaluate the technical and educational value of head-mounted AR in cerebrovascular procedures. This is a single-center retrospective study of patients who underwent open surgery for cranial and spinal cerebrovascular lesions between April and August 2022. In all cases, the Medivis Surgical AR platform and HoloLens 2 were used for preoperative and intraoperative (preincision) planning. Surgical plan adjustment due to the use of head-mounted AR and subjective educational value of the tool were recorded. A total of 33 patients and 35 cerebrovascular neurosurgical procedures were analyzed. Procedures included 12 intracranial aneurysm clippings, 6 brain and 1 spinal arteriovenous malformation resections, 2 cranial dural arteriovenous fistula obliterations, 3 carotid endarterectomies, two extracranial-intracranial direct bypasses, two encephaloduroangiosynostosis for Moyamoya disease, 1 biopsy of the superficial temporal artery, 2 microvascular decompressions, 2 cavernoma resections, 1 combined intracranial aneurysm clipping and encephaloduroangiosynostosis for Moyamoya disease, and 1 percutaneous feeder catheterization for arteriovenous malformation embolization. Minor changes in the surgical plan were recorded in 16 of 35 procedures (45.7%). Subjective educational value was scored as "very helpful" for cranial, spinal arteriovenous malformations, and carotid endarterectomies; "helpful" for intracranial aneurysm, dural arteriovenous fistulas, direct bypass, encephaloduroangiosynostosis, and superficial temporal artery-biopsy; and "not helpful" for cavernoma resection and microvascular decompression. Head-mounted AR can be used in cerebrovascular neurosurgery as an adjunctive tool that might influence surgical strategy, enable 3-dimensional understanding of complex anatomy, and provide great educational value in selected cases.


Scaling-up services for psychosis, depression and epilepsy in sub-Saharan Africa and South Asia: development and application of a mental health systems planning tool (OneHealth).
Although financing represents a critical component of health system strengthening and also a defining concern of efforts to move towards universal health coverage, many countries lack the tools and capacity to plan effectively for service scale-up. As part of a multi-country collaborative study (the Emerald project), we set out to develop, test and apply a fully integrated health systems resource planning and health impact tool for mental, neurological and substance use (MNS) disorders. A new module of the existing UN strategic planning OneHealth Tool was developed, which identifies health system resources required to scale-up a range of specified interventions for MNS disorders and also projects expected health gains at the population level. We conducted local capacity-building in its use, as well as stakeholder consultations, then tested and calibrated all model parameters, and applied the tool to three priority mental and neurological disorders (psychosis, depression and epilepsy) in six low- and middle-income countries. Resource needs for scaling-up mental health services to reach desired coverage goals are substantial compared with the current allocation of resources in the six represented countries but are not large in absolute terms. In four of the Emerald study countries (Ethiopia, India, Nepal and Uganda), the cost of delivering key interventions for psychosis, depression and epilepsy at existing treatment coverage is estimated at US$ 0.06-0.33 per capita of total population per year (in Nigeria and South Africa it is US$ 1.36-1.92). By comparison, the projected cost per capita at target levels of coverage approaches US$ 5 per capita in Nigeria and South Africa, and ranges from US$ 0.14-1.27 in the other four countries. Implementation of such a package of care at target levels of coverage is expected to yield between 291 and 947 healthy life years per one million populations, which represents a substantial health gain for the currently neglected and underserved sub-populations suffering from psychosis, depression and epilepsy. This newly developed and validated module of OneHealth tool can be used, especially within the context of integrated health planning at the national level, to generate contextualised estimates of the resource needs, costs and health impacts of scaled-up mental health service delivery.


The mistaken diagnosis of child abuse. A form of medical abuse?
The suspected diagnosis of child abuse may prove to be unfounded. Reports in the literature have focused on unusual diseases and folk medicine practices that may mimic abuse. We report ten cases where allegations of abuse were lodged against parents because the treating physicians in the emergency room mistook life-threatening illness or postmortem artifacts for inflicted injury. In all cases the families were from the inner city, and with two exceptions the involved institutions were small hospitals without pediatric personnel present in the emergency department. Although the histories related by the parents were in all cases truthful and consistent with the results of physical examinations of the child, the involved physicians failed to make a correct diagnosis. Not only a lack of experience with severe childhood illness and death but also an attitude of suspicion and/or hostility probably contributed to these misdiagnoses.


Diagnosis of right ventricular cardiac sarcoidosis with cardiac magnetic resonance in a patient presenting with ventricular tachycardia.
Sarcoidosis patients often have myocardial involvement, however, very few have clinically significant cardiac disease and ventricular tachycardia as the initial presentation is exceedingly rare. We report the case of a middle-aged male with symptomatic but clinically stable ventricular tachycardia. Chest radiograph, computed tomography, and positron emission tomography demonstrated pulmonary and mediastinal abnormalities but no definitive etiology for his arrhythmia. Transthoracic echocardiogram revealed the nonspecific cardiac abnormalities of right ventricular dilation and septal flattening. Cardiac magnetic resonance demonstrated delayed enhancement and akinesia of the right ventricular free and inferior walls--virtually diagnostic of an infiltrative myocardial disease. The diagnosis was then verified with transbronchial biopsy showing noncaseating granulomas consistent with sarcoidosis. In conclusion, this case illustrates an unusual presentation of sarcoidosis and demonstrates how the diagnosis can be made using cardiac magnetic resonance alongside transbronchial biopsy.


Estrogen receptor α plays an important role in Cushing's syndrome during pregnancy.
Cushing's syndrome (CS) during pregnancy is very rare with a few cases reported in the literature. Of great interest, some cases of CS during pregnancy spontaneously resolve after delivery. Most studies suggest that aberrant luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor (LHCGR) seems to play a critical role in the pathogenesis of CS during pregnancy. However, not all women during pregnancy are observed cortisol hypersecretion. Moreover, some cases of adrenal tumors or macronodular hyperplasia with LHCGR expressed, have no response to hCG or LH. Therefore, alternative pathogenic mechanisms are indicated. It has been recently reported that estrogen binding to estrogen receptor α (ERα) could enhance the adrenocortical adenocarcinoma (ACC) cell proliferation. Herein, we hypothesize that ERα is probably involved in CS development during pregnancy. Better understanding of the possible mechanism of ERα on cortisol production and adrenocortical tumorigenesis will contribute to the diagnosis and treatment of CS during pregnancy.


[Esophageal carcinoma: transthoracic esophagectomy with regional lymphadenectomy and reconstruction with deferred priority].
In a retrospective analysis the risks were assessed of transthoracic oesophagectomy with mediastinectomy and regional lymphadenectomy followed 48-72 hours later by an abdomino-cervical operation with supra-pancreatic lymphadenectomy, retrosternal gastric interposition and cervical oesophageal stump anastomosis. Results in this group of 37 patients were compared with those in a group of 42 patients who had undergone a transmediastinal oesophagectomy (without thoracotomy) and immediate reconstruction. The 30-day death rate was 8.1% in the former (group I) and 7.1% in the latter (group II), total hospital death rate 10.8% and 11.9%, respectively. The complication rate was similar in the two groups, as was the recorded operative stress. The results indicate that the risk of an oncologically indicated oesophagectomy with regional lymphadenectomy is no greater than that of a palliative transmediastinal oesophagectomy.


5-Hydroxytryptamine2A receptors expressed in rat renal mesangial cells inhibit cyclic AMP accumulation.
Second messenger coupling of the 5-hydroxytryptamine (5-HT)2A receptor endogenous to cultured rat glomerular mesangial cells was studied. 5-HT induced an increase in total inositol phosphate levels (EC50 = 265 +/- 55 nM, maximum stimulation = 150 +/- 23%). That effect was sensitive to antagonists of the 5-HT2A receptor and was insensitive to pertussis toxin at doses that eliminated detectable pertussis toxin substrate, as determined by membrane ADP-ribosylation. Surprisingly, 5-HT also induced an inhibition of forskolin-stimulated cAMP accumulation (55 +/- 6%, IC50 = 5 +/- 3 nM). This effect was competitively antagonized by the 5-HT2A receptor antagonists ketanserin, ritanserin, and spiperone and could be produced by the 5-HT2 receptor agonists alpha-methyl-5-HT (66 +/- 13%, IC50 = 23 +/- 14 nM) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (65 +/- 4%, IC50 = 14 +/- 7 nM). The inhibition of cAMP accumulation occurred in the presence of a number of agents that either stimulate or inhibit protein kinase C activity, arachidonic acid metabolism, or Ca2+ mobilization. In isolated membranes, 5-HT induced a 36 +/- 5% inhibition of adenylyl cyclase activity (IC50 = 8 +/- 4 nM). Inhibition of cAMP accumulation in intact cells and of adenylyl cyclase activity in washed membranes was (> 50%) sensitive to pertussis toxin, implicating Gi alpha or Go alpha subunits in the inhibitory signal. These data suggest that the 5-HT2A receptor can be permissive in its coupling to G proteins and second messengers.


Emotion Recognition for Human-Robot Interaction: Recent Advances and Future Perspectives.
A fascinating challenge in the field of human-robot interaction is the possibility to endow robots with emotional intelligence in order to make the interaction more intuitive, genuine, and natural. To achieve this, a critical point is the capability of the robot to infer and interpret human emotions. Emotion recognition has been widely explored in the broader fields of human-machine interaction and affective computing. Here, we report recent advances in emotion recognition, with particular regard to the human-robot interaction context. Our aim is to review the state of the art of currently adopted emotional models, interaction modalities, and classification strategies and offer our point of view on future developments and critical issues. We focus on facial expressions, body poses and kinematics, voice, brain activity, and peripheral physiological responses, also providing a list of available datasets containing data from these modalities.


Anxiety, not regulation tendency, predicts how individuals regulate in the laboratory: An exploratory comparison of self-report and psychophysiology.
Anxiety influences how individuals experience and regulate emotions in a variety of ways. For example, individuals with lower anxiety tend to cognitively reframe (reappraise) negative emotion and those with higher anxiety tend to suppress negative emotion. Research has also investigated these individual differences with psychophysiology. These lines of research assume coherence between how individuals regulate outside the laboratory, typically measured with self-report, and how they regulate during an experiment. Indeed, performance during experiments is interpreted as an indication of future behavior outside the laboratory, yet this relationship is seldom directly explored. To address this gap, we computed psychophysiological profiles of uninstructed (natural) regulation in the laboratory and explored the coherence between these profiles and a) self-reported anxiety and b) self-reported regulation tendency. Participants viewed negative images and were instructed to reappraise, suppress or naturally engage. Electrodermal and facial electromyography signals were recorded to compute a multivariate psychophysiological profile of regulation. Participants with lower anxiety exhibited similar profiles when naturally regulating and following instructions to reappraise, suggesting they naturally reappraised more. Participants with higher anxiety exhibited similar profiles when naturally regulating and following instructions to suppress, suggesting they naturally suppressed more. However, there was no association between self-reported reappraisal or suppression tendency and psychophysiology. These exploratory results indicate that anxiety, but not regulation tendency, predicts how individuals regulate emotion in the laboratory. These findings suggest that how individuals report regulating in the real world does not map on to how they regulate in the laboratory. Taken together, this underscores the importance of developing emotion-regulation interventions and paradigms that more closely align to and predict real-world outcomes.


A pilot study for a prospective, randomized, double-blind trial of the influence of anesthetic depth on long-term outcome.
Deep general anesthesia has been associated with increased mortality in 5 observational studies. The association may be causal or an epiphenomenon due to increased anesthetic sensitivity in high-risk patients. We conducted a pilot study to assess the feasibility of performing a definitive randomized controlled trial. The aims of the study were to determine whether anesthetic depth targeting in a high-risk group was feasible and to document anesthetic doses and arterial blood pressures associated with "deep" and "light" general anesthesia. ASA physical status III and IV patients, aged ≥60 years, having surgery lasting ≥2 hours, with expected hospital stay ≥2 days, and receiving general anesthesia were randomly allocated to a Bispectral Index (BIS) or spectral entropy (SE) target of 35 ("low" group) or 50 ("high" group). The primary end point was mean BIS or SE. Secondary end points were postanesthesia care unit length of stay and pain scores, quality of recovery score, hospital length of stay, postoperative complications, and death. A composite end point of postoperative complications (pneumonia, myocardial infarction, stroke, pulmonary embolism, heart failure, and death) was determined at 1 year. One hundred twenty-five patients were recruited. The mean of the median BIS/SE values for each patient during the maintenance phase of anesthesia in the low and high groups was significantly different: 39 vs 48 (mean difference 8 [95% confidence interval {CI95}, 6 to 10], P < 0.001). There was also a significant difference in mean volatile anesthetic administration (minimum alveolar concentration): 0.98 vs 0.64 (mean difference -0.35 [CI95, -0.44 to -0.26], P < 0.001) and target propofol concentrations: 4.0 vs 3.1 μg/mL (mean difference -0.8 [CI95, -1.2 to -0.3], P = 0.004). Intraoperative mean arterial blood pressures were similar (85 vs 87 mm Hg; mean difference 2 [CI95, -2 to 6], P = 0.86), and there were no differences in short-term recovery characteristics or hospital length of stay. There was a significant difference in the incidence of wound infection at 30 days (13% vs 3%; risk difference -10% [CI95, -21 to -0.1], P = 0.04). At 1 year, the composite rates of complications in the low and high groups were 28% and 17% (risk difference -11 [CI95, -25 to 4], P = 0.15) and mortality rates were 12% and 9%, respectively (risk difference -2 [CI95, -14 to 9], P = 0.70). This pilot study demonstrated that depth of anesthesia targeting with BIS or SE was achievable in a high-risk population with adequate separation of processed electroencephalogram monitor targets. The expected incidence of postoperative complications and mortality occurred. We conclude that a large, multicenter, randomized controlled trial is feasible.


Vaccination of mice with lipopolysaccharide (LPS) and LPS-derived immuno-conjugates from Leptospira interrogans.
Mice were vaccinated with lipopolysaccharide (LPS) from Leptospira interrogans serovar pomona or hardjo, or with the polysaccharide (PS) fraction of the LPS, or with an immunoconjugate of PS and diphtheria toxoid (DT). Maximum agglutinin titres were found 6-10 weeks after vaccination with LPS or PS-DT conjugate; the latter elicited antibody titres at least 10 times higher than those produced in response to LPS. Animals failed to react significantly to PS. Titres elicited by antigens of serovar pomona were higher than those elicited by serovar hardjo.


Intraocular pressure elevation after intravitreal triamcinolone acetonide injection in a Chinese population.
To study the prevalence and risk factors of intraocular pressure (IOP) elevation and refractory IOP elevation after a single 4 mg intravitreal triamcinolone acetonide (IVTA) injection in a Chinese population. Retrospective, observational case series. Retrospective chart review of all the patients who received an IVTA injection at one medical center from January 2003 through June 2005. A postoperative IOP increase of more than 6 mm Hg was defined as an IOP elevation. Postoperative IOP elevation that could not be controlled by glaucoma medications was defined as refractory IOP elevation. Sixty-four (43.5%) of the 147 enrolled patients experienced IOP elevation. Males had a higher risk of IOP elevation, with an odds ratio (OR) of 3.17 (95% confidence interval [CI], 1.38 to 7.27; P = .006), after adjusting for age, glaucoma history, and diagnosis of retinal disease. Patients 55 years of age and younger had a larger magnitude of IOP elevation than those older than 55 years (11.2 +/- 10.1 mm Hg vs 7.3 +/- 7.7 mm Hg; P = .020). Ten patients (6.8%) had refractory IOP elevation, and those 55 years of age or younger had a higher risk of refractory IOP elevation compared with those older than 55 years, with an OR of 8.16 (95% CI, 1.67 to 39.81; P = .009), after adjusting for preoperative IOP and diagnosis of retinal disease. Elevated IOP after IVTA injection is common in this Chinese population. Male patients have a higher risk of IOP elevation. Younger patients should be monitored carefully after IVTA injection because they exhibit a greater magnitude of IOP elevation and have an increased chance of developing refractory IOP elevation.


Odorless inhalant toxic encephalopathy in developing countries household: Gas geyser syndrome.
Liquefied petroleum gas geysers are used very frequently for heating water in developing countries such as India. However, these gas geysers emit various toxic gases; one among them is colorless, odorless carbon monoxide (CO). In the past few years, there were reports of unexplained loss of consciousness in the bathroom. However, the exact cause for these episodes has been recognized as toxic encephalopathy due to toxic gases inhalation mainly CO. To analyze the clinical profile and outcome of patients brought with loss of consciousness in the bathroom while bathing using gas geyser. Case records of patients with the diagnosis of gas geyser syndrome from 2013 to 2015 were retrieved and analyzed. Twenty-four cases were identified and included in the study. This was a retrospective, descriptive study. Twenty-four patients were brought to our Emergency Department with loss of consciousness in the bathroom while bathing. Twenty-one cases had loss of consciousness during bathing and recovered spontaneously. Two cases were found dead in the bathroom and were brought to the Department of Forensic Medicine for postmortem. One case was brought in deep altered state of consciousness and succumbed to illness within 1 week. Awareness regarding CO intoxication due to usage of ill-fitted, ill-ventilated gas geyser is necessary as they are entirely preventable conditions.


Risk factors associated with gastric cancer in Mexico: education, breakfast and chili.
the aim of the study was to use a validated questionnaire to identify factors associated with the development of gastric cancer (GC) in the Mexican population. the study included cases and controls that were paired by sex and ± 10 years of age at diagnosis. In relation to cases, 46 patients with a confirmed histopathological diagnosis of adenocarcinoma-type GC, as reported in the hospital records, were selected, and 46 blood bank donors from the same hospital were included as controls. The previously validated Questionnaire to Find Factors Associated with Gastric Cancer (QUFA-GC©) was used to collect data. Odds ratio (OR) and 95% confidence interval (IC) were estimated via univariate analysis (paired OR). Multivariate analysis was performed by logistic regression. A decision tree was constructed using the J48 algorithm. an association was found by univariate analysis between GC risk and a lack of formal education, having smoked for ≥ 10 years, eating rapidly, consuming very hot food and drinks, a non-suitable breakfast within two hours of waking, pickled food and capsaicin. In contrast, a protective association against GC was found with taking recreational exercise and consuming fresh fruit and vegetables. No association was found between the development of GC and having an income that reflected poverty, using a refrigerator, perception of the omission of breakfast and time period of alcoholism. In the final multivariate analysis model, having no formal education (OR = 17.47, 95% CI = 5.17-76.69), consuming a non-suitable breakfast within two hours of waking (OR = 8.99, 95% CI = 2.85-35.50) and the consumption of capsaicin ˃ 29.9 mg capsaicin per day (OR = 3.77, 95% CI = 1.21-13.11) were factors associated with GC. an association was found by multivariate analysis between the presence of GC and education, type of breakfast and the consumption of capsaicin. These variables are susceptible to intervention and can be identified via the QUFA-GC


Long-lived nuclear spin states in methyl groups and quantum-rotor-induced polarization.
Substances containing rapidly rotating methyl groups may exhibit long-lived states (LLSs) in solution, with relaxation times substantially longer than the conventional spin-lattice relaxation time T1. The states become long-lived through rapid internal rotation of the CH3 group, which imposes an approximate symmetry on the fluctuating nuclear spin interactions. In the case of very low CH3 rotational barriers, a hyperpolarized LLS is populated by thermal equilibration at liquid helium temperature. Following dissolution, cross-relaxation of the hyperpolarized LLS, induced by heteronuclear dipolar couplings, generates strongly enhanced antiphase NMR signals. This mechanism explains the NMR signal enhancements observed for (13)C-γ-picoline (Icker, M.; Berger, S. J. Magn. Reson. 2012, 219, 1-3).


[Studying the possibility of respiratory immunization against tick-borne encephalitis].
There are known 3 likely mechanisms of virus conveyance into the central nervous system (CNS). These include hematogenic penetration, spread along the peripheral nerves, and the olfactory pathway which begins from the infected olfactory neuroepithelial cells. The possibility of viral spread into CNS via the olfactory pathway was shown for the representatives of togaviruses, herpesviruses, coronaviruses, rhabdoviruses, and for some others. This study suggests that the olfactory pathway of viral conveyance into CNS may be blocked by specific mucosal antibodies in the nasal mucosa. The recombinant TK- variant of WR vaccinia strain with inserted genes coding structural and nonstructural proteins of TBE virus is accumulated in the branches of the respiratory tract only while the parenteral vaccinia strain is detected in the brain regions, spleen, respiratory tract, and in blood. The protective activity of recombinant strain and inactivated TBE vaccine after mice immunization by escarification or intranasally, or subcutaneously was comparatively studied. The findings indicate that intranasal immunization by recombinant strain is the most protective against intraperitoneal challenge by TBE virus. The mucosal and humoral immune response that was induced by intranasal immunization seems to provide the highest levels of protection, which was experimentally observed.


Comparison of sCIM and Other Phenotypic Detection Methods for Carbapenemase-Producing Enterobacterales.
Rapid detection and reporting of carbapenemase-producing Enterobacterales (CPE) is one of the top priorities of clinical microbiology laboratories. The Clinical and Laboratory Standards Institute recommends the modified carbapenem inactivation method (mCIM) as the preferred method for this purpose, but it requires a broth incubation process which can be cumbersome. Here, we compared the performance of mCIM with three alternative rapid CPE detection methods against a collection of genetically defined CPE, with most carrying blaIMP, and non-CPE clinical isolates. The sensitivities of mCIM, simplified carbapenem inactivation method (sCIM), Rapidec Carba NP, and NG-Test Carba 5 were 98.0%, 54.9%, 90.2%, and 72.5%, whereas the specificities were 89.5%, 84.2%, 89.5%, and 100%, respectively. Modification of the interpretive criteria of sCIM increased its sensitivity to 88.2% and specificity to 89.5%. The results suggest that mCIM is currently the optimal method for CPE detection in an epidemiological setting where CPE-producing IMP group carbapenemase is predominant. While sCIM is easier to perform, it requires further validation before it can be widely adopted as an alternative to mCIM in the clinical laboratory. IMPORTANCE Simple identification methods for carbapenemase-producing Enterobacterales are required for the clinical laboratory. The simplified carbapenem inactivation method (sCIM) is a carbapenemase detection method that can be performed with less hands-on time than mCIM, but its sensitivity and specificity were suboptimal compared with other phenotypic detection methods when tested against a collection of IMP-producing CPE. Insufficient inactivation of imipenem from inadequate inoculation was suspected as the cause. While sCIM is easier to perform, it requires optimization before it can be widely adopted as an alternative to mCIM in the clinical laboratory.


Synthesis and characterization of designed BMHP1-derived self-assembling peptides for tissue engineering applications.
The importance of self-assembling peptides (SAPs) in regenerative medicine is becoming increasingly recognized. The propensity of SAPs to form nanostructured fibers is governed by multiple forces including hydrogen bonds, hydrophobic interactions and π-π aromatic interactions among side chains of the amino acids. Single residue modifications in SAP sequences can significantly affect these forces. BMHP1-derived SAPs is a class of biotinylated oligopeptides, which self-assemble in β-structured fibers to form a self-healing hydrogel. In the current study, selected modifications in previously described BMHP1-derived SAPs were designed in order to investigate the influence of modified residues on self-assembly kinetics and scaffold formation properties. The Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis demonstrated the secondary structure (β-sheet) formation in all modified SAP sequences, whereas atomic force microscopy (AFM) analysis further confirmed the presence of nanofibers. Furthermore, the fiber shape and dimension analysis by AFM showed flattened and twisted fiber morphology ranging from ∼8 nm to ∼70 nm. The mechanical properties of the pre-assembled and post assembled solution were investigated by rheometry. The shear-thinning behavior and rapid re-healing properties of the pre-assembled solutions make them a preferable choice for injectable scaffolds. The wide range of stiffnesses (G')--from ∼1000 to ∼27,000 Pa--exhibited by the post-assembled scaffolds demonstrated their potential for a variety of tissue engineering applications. The extra cellular matrix (ECM) mimicking (physically and chemically) properties of SAP scaffolds enhanced cell adhesion and proliferation. The capability of the scaffold to facilitate murine neural stem cell (mNSC) proliferation was evaluated in vitro: the increased mNSCs adhesion and proliferation demonstrated the potential of newly synthesized SAPs for regenerative medicine approaches.


Renal Leiomyosarcoma: Case Report and Review of the Literature.
Leiomyosarcoma of the kidney is a rare entity, and our understanding of this type of renal sarcomas is limited. A 46-year-old Caucasian male presented with a chief complaint of right flank pain for one month. He came to our facility for an additional opinion regarding the management of his renal mass. Computed tomography (CT) of the abdomen showed an enhancing, heterogeneous right renal mass, consistent with the features of renal cell carcinoma (RCC). Robotic-assisted total nephrectomy of the right kidney revealed a tan mass with central necrosis that involved the upper pole of the kidney. Based on gross specimen observation and immunochemical analysis, the patient was diagnosed with high-grade leiomyosarcoma. While the prognosis is poor, radical nephrectomy remains the treatment of choice. The potential benefits of adjuvant therapy should be discussed with selected patients.


Electromagnetic navigation-guided versus computed tomography-guided percutaneous localization of small lung nodules before uniportal video-assisted thoracoscopic surgery: a propensity score-matched analysis.
An optimal method for preoperative localization of small lung nodules is yet to be established, and there are few comparative studies in the literature. In the present study, we aimed to compare electromagnetic navigation-guided and computed tomography (CT)-guided methods of percutaneous transthoracic localization. The clinical, radiographic, surgical and pathological data of patients who underwent electromagnetic navigation-guided localization (EMNGL) and CT-guided localization (CTGL) before uniportal video-assisted thoracic surgery (VATS) were reviewed. Propensity score matching analysis was performed to compare the localization and surgical results. After matching, 25 EMNGL and 50 CTGL patients were included in the analysis. In the CTGL group, pulmonary haemorrhage and pneumothorax were noted in 56% and 34% of patients, respectively, on postprocedural CT scans. Successful localization was achieved in 96% and 100% of patients in the EMNGL and CTGL groups, respectively (P = 0.333). The median time in the operation room was significantly shorter in the CTGL group {142.5 [interquartile range (IQR) 123.8-175.0] vs 205.0 [IQR 177.5-290.0] min, P < 0.001}. In contrast, EMNGL significantly decreased the total time [205.0 (IQR 177.5-290.0) vs 324.0 (IQR 228.3-374.0) min, P = 0.002]. The median duration of chest drainage was 1 day shorter in the EMNGL group [2.0 (IQR 1.5-2.5) vs 3.0 (IQR 2.0-3.0), P = 0.002]; the surgical complication rates were comparable between the 2 groups. The localization and surgical results were similar between the EMNGL and CTGL groups. EMNGL is comparable to conventional CTGL with respect to preoperative localization of small lung nodules before uniportal VATS.


Comprehensive Genomic Profiling Reveals Diverse but Actionable Molecular Portfolios across Hematologic Malignancies: Implications for Next Generation Clinical Trials.
Background: The translation of genomic discoveries to the clinic is the cornerstone of precision medicine. However, incorporating next generation sequencing (NGS) of hematologic malignancies into clinical management remains limited. Methods: We describe 235 patients who underwent integrated NGS profiling (406 genes) and analyze the alterations and their potential actionability. Results: Overall, 227 patients (96.5%) had adequate tissue. Most common diagnoses included myelodysplastic syndrome (22.9%), chronic lymphocytic leukemia (17.2%), non-Hodgkin lymphoma (13.2%), acute myeloid leukemia (11%), myeloproliferative neoplasm (9.2%), acute lymphoblastic leukemia (8.8%), and multiple myeloma (7.5%). Most patients (N = 197/227 (87%)) harbored ≥1 genomic alteration(s); 170/227 (75%), ≥1 potentially actionable alteration(s) targetable by an FDA-approved (mostly off-label) or an investigational agent. Altogether, 546 distinct alterations were seen, most commonly involving TP53 (10.8%), TET2 (4.6%), and DNMT3A (4.2%). The median tumor mutational burden (TMB) was low (1.7 alterations/megabase); 12% of patients had intermediate or high TMB (higher TMB correlates with favorable response to anti-PD1/PDL1 inhibition in solid tumors). In conclusion, 96.5% of patients with hematologic malignancies have adequate tissue for comprehensive genomic profiling. Most patients had unique molecular signatures, and 75% had alterations that may be pharmacologically tractable with gene- or immune-targeted agents.


The microbiome and the lung.
Investigation of the human microbiome has become an important field of research facilitated by advances in sequencing technologies. The lung, which is one of the latest body sites being explored for the characterization of human-associated microbial communities, has a microbiome that is suspected to play a substantial role in health and disease. In this review, we provide an overview of the basics of microbiome studies. Challenges in the study of the lung microbiome are highlighted, and further attention is called to the optimization and standardization of methodologies to explore the role of the lung microbiome in health and disease. We also provide examples of lung microbial communities associated with disease or infection status and discuss the role of fungal species in the lung. Finally, we review studies demonstrating that the environmental microbiome can influence lung health and disease, such as the finding that the diversity of microbial exposure correlates inversely with the development of childhood asthma.


Risk Factors for Allograft Subsidence Following Anterior Cervical Discectomy and Fusion.
The purpose this study was to precisely characterize patterns of allograft subsidence following anterior cervical discectomy and fusion (ACDF) utilizing computed tomography scans, determine risk factors for cervical allograft subsidence, and investigate the impact of subsidence on pseudarthrosis rates. We performed a retrospective review of patients undergoing 1-to 3-level ACDF utilizing allograft interbodies with anterior plating between 2011 and 2019. Subsidence measurements were performed by 2 independent reviewers on computed tomography scans obtained 6 months postoperatively. Subsidence was then classified as mild if subsidence into the inferior and superior endplates were both ≤2 mm, moderate if the worst subsidence into the inferior- or superior endplate was between 2 and 4 mm, or severe if the worst subsidence into the inferior- or superior endplate was ≥4 mm. Multivariate analysis was performed to identify risk factors for the development of subsidence. We identified 98 patients (152 levels) for inclusion. A total of 73 levels demonstrated mild subsidence (≤2 mm), 61 demonstrated moderate subsidence (2-4 mm), and 18 demonstrated severe subsidence (≥4 mm). On multivariate analysis, risk factors for severe subsidence included excessive vertebral endplate resection and lower screw tip to vertebral body height ratio. Severe subsidence was associated with an increased rate of pseudarthrosis (94.1% vs. 13.6%) without an associated increase in reoperation rate. Following ACDF with allograft interbodies, 50% of interbodies will subside >2 mm and 10% of interbodies will subside >4 mm. Risk factors for severe subsidence should be mitigated to decrease the risk of pseudarthrosis.


Results of total hip arthroplasty in Gaucher's disease patients.
There is controversy regarding the success of total hip arthroplasty (THA) in patients with Gaucher's disease. We present a retrospective study of nine total hip replacements in six patients (four primary THAs and five revisions). Four were female and two were male. All patients were of white ethnic origin. Five hips have required revision surgery for loosened implants (four once only and one twice). The average age at the time of primary THA was 35.3 years (13-54). The average duration between primary THA and first revision was 11.4 years (6-19). The duration between first and second revision in one hip was six years. The follow-up ranged between 2.5 years to 19 years. One patient developed superficial infection postoperatively which settled with wound debridement and antibiotics. Excessive peri-operative blood loss was noted in three patients.


Urothelium-Specific Deletion of Connexin43 in the Mouse Urinary Bladder Alters Distension-Induced ATP Release and Voiding Behavior.
Connexin43 (Cx43), the main gap junction and hemichannel forming protein in the urinary bladder, participates in the regulation of bladder motor and sensory functions and has been reported as an important modulator of day-night variations in functional bladder capacity. However, because Cx43 is expressed throughout the bladder, the actual role played by the detrusor and the urothelial Cx43 is still unknown. For this purpose, we generated urothelium-specific Cx43 knockout (uCx43KO) mice using Cre-LoxP system. We evaluated the day-night micturition pattern and the urothelial Cx43 hemichannel function of the uCx43KO mice by measuring luminal ATP release after bladder distention. In wild-type (WT) mice, distention-induced ATP release was elevated, and functional bladder capacity was decreased in the animals' active phase (nighttime) when Cx43 expression was also high compared to levels measured in the sleep phase (daytime). These day-night differences in urothelial ATP release and functional bladder capacity were attenuated in uCx43KO mice that, in the active phase, displayed lower ATP release and higher functional bladder capacity than WT mice. These findings indicate that urothelial Cx43 mediated ATP signaling and coordination of urothelial activity are essential for proper perception and regulation of responses to bladder distension in the animals' awake, active phase.


Evidence for a ligand-mediated positive selection signal in differentiation to a mature B cell.
Positive selection is required for B cell differentiation, as indicated by the requirement for expression of the pre-B cell receptor (pre-BCR) and the BCR at the pre-B and immature B cell stages, respectively. Positive selection mediated by a tonic signal from these receptors is sufficient to drive B cell differentiation beyond the pre-B and immature B cell stages, but it is unclear whether additional positive selection signals are required for differentiation to a mature B-2 cell. We have identified a population of Ig transgenic B cells that differentiatively arrest at a transitional B cell stage in the spleen. They exhibit no evidence of Ag encounter or negative selection and can differentiate to mature B-2 cells in vivo upon weak BCR stimulation or adoptive transfer to irradiated hosts. These data are consistent with a requirement for a ligand-mediated BCR signal for differentiation to a mature B-2 cell.


Connections of the posterior thalamic region with the auditory ectosylvian cortex in the dog.
The purpose of the present study was to define auditory cortical areas in the dog on the basis of thalamocortical connectivity patterns. Connections between the posterior thalamic region and auditory ectosylvian cortex were studied using axonally transported tracers: fluorochromes and biotinylated dextran amine. Cyto- and chemoarchitecture provided grounds for the division of the posterior thalamic region into three complexes, medial geniculate body (MGB), posterior nuclei (Po), and lateromedial and suprageniculate nuclei (LM-Sg). Distinctive cytoarchitectonic features and the distribution of dominant thalamocortical connections (determined quantitatively) allowed us to define four ectosylvian areas: middle (EM), anterior (EA), posterior (EP), and composite (CE). We found that each area was a place of convergence for projections from five to eleven nuclei of the three thalamic complexes, with dominant projections derived from one or two nuclei. Dominant topographical projections from the ventral nucleus to area EM confirmed physiological reports that it may be considered a primary auditory area (AI). We found the anterior part of the EM to be distinct in having unique strong connections with the deep dorsal MGB nucleus. Area EA, which receives dominant projections from the lateral Po (Pol) and medial MGB nuclei, as well as area EP, which receives dominant connections from the dorsal caudal MGB nucleus, compose two parasensory areas. Area CE receives dominant projections from the extrageniculate nuclei, anterior region of the LM-Sg, and Pol, supplemented with an input from the somatosensory VP complex, and may be considered a polymodal association area.


Truncated JFH1 E2 Protein: Is it Reliable to be Used in Diagnostic ELISA Test and as a Protein-Based Vaccine Candidate?
HCV E2 glycoprotein is one of the most attractive proteins for designing an effective vaccine. Deletion of hydrophobic carboxyl-terminal region of this protein is necessary for its secretion, especially when it is expressed in E-coli. In this study we expressed this protein in truncated form and evaluated its application in developing an ELISA test and induction of humoral response in immunized mice. The purpose of this study was expression of HCV truncated E2 protein from JFH1 strain in E-coli BL21(DE3) and evaluation of its antigenicity. Truncated E2 region from HCV genotype 2a (JFH1) was amplified by PCR and cloned into a pET28a (+) vector and was used to transform the E-coli DH5α strain. The recombinant E2 protein was evaluated both in an ELISA test and induction of humoral immunity in mice. Truncated E2 protein was expressed in BL21(DE3). Its specific antibody was detected in serum samples from HCV infected patients. Also, it could elicit a significant humoral immunity in mice. Truncated form of E2 protein which has been expressed in E-coli could be used as an effective antigen both in diagnostic tests such as ELISA and also, as a protein-based vaccine candidate.


Early percutaneous transluminal coronary angioplasty or coronary bypass surgery following thrombolytic treatment of acute myocardial infarction.
Coronary reocclusion rates following intracoronary streptokinase (IC-SK) infusion remain significantly high despite anticoagulation. Early intervention by coronary angioplasty (PTCA) or coronary bypass surgery (CABG) was advocated to minimize such risk and/or maintain coronary reperfusion. Of 71 consecutive patients (60 men, 11 women; mean age, 54.9 years) who underwent IC-SK infusion for acute myocardial infarction (MI) 50 had early CABG, 18 had PTCA, and three had both procedures. Sixty-four of the 71 had successful thrombolysis. Thirty-six patients had either CABG or PTCA within three days, 22 patients within seven days, and 13 patients within two weeks. There was no immediate or in-hospital mortality, and all patients remained alive through the follow-up period of three to 36 months. Functional class (FC) 1 was achieved in 45 patients, FC 2 in 22 patients, FC 3 in three patients, and FC 4 in one patient. Sixty-seven patients (94 percent) were free of chest pain through the follow-up period. These data suggest that early intervention by CABG and/or PTCA in suitable candidates could be achieved with reduced risk and expected to yield favorable results. This favorable trend could be related to maintenance of myocardial perfusion by these procedures, initially induced by thrombolysis. Long-term, large-scale studies are needed to confirm the role of optimal timing of such procedures, but we believe that such results indicate that early revascularization yields promising results.


Disability after encephalitis: development and validation of a new outcome score.
To develop a simple tool for assessing the severity of disability resulting from Japanese encephalitis and whether, as a result, a child is likely to be dependent. A new outcome score based on a 15-item questionnaire was developed after a literature review, examination of current assessment tools, discussion with experts and a pilot study. The score was used to evaluate 100 children in Malaysia (56 Japanese encephalitis patients, 2 patients with encephalitis of unknown etiology and 42 controls) and 95 in India (36 Japanese encephalitis patients, 41 patients with encephalitis of unknown etiology and 18 controls). Inter- and intra-observer variability in the outcome score was determined and the score was compared with full clinical assessment. There was good inter-observer agreement on using the new score to identify likely dependency (Kappa = 0.942 for Malaysian children; Kappa = 0.786 for Indian children) and good intra-observer agreement (Kappa = 1.000 and 0.902, respectively). In addition, agreement between the new score and clinical assessment was also good (Kappa = 0.906 and 0.762, respectively). The sensitivity and specificity of the new score for identifying children likely to be dependent were 100% and 98.4% in Malaysia and 100% and 93.8% in India. Positive and negative predictive values were 84.2% and 100% in Malaysia and 65.6% and 100% in India. The new tool for assessing disability in children after Japanese encephalitis was simple to use and scores correlated well with clinical assessment.


STAT 1alpha/1beta, STAT 3 and STAT 5: expression and association with c-MET and EGF-receptor in long-term cultures of human hepatocytes.
Long-term cultures of human hepatocytes were maintained serum-free in a chemically defined medium in the presence of HGF and EGF for up to 30 days. STAT 1alpha/1beta, STAT 3, and STAT 5 were present and tyrosine phosphorylated throughout the culture period in the cytosol as well as the nucleus. We show by co-immunoprecipitation that a portion of the cellular pools of STAT 1alpha/1beta and STAT 5 is physically associated with c-MET and EGF-receptor. Co-immunoprecipitation of STAT 3 with STAT 5 did occur in the cytosol but not in the nucleus, suggesting dimerization of the two STAT family members. The observed differences of protein amounts and tyrosine phosphorylation between cytosol and nucleus, the association of STAT proteins with EGF-receptor and c-MET and with each other may all be involved in regulating the activity of the STAT transcription factors. It is intriguing to speculate that STAT 5 may have a modulating role in the regulation of STAT 3 activity.


On modeling correlated random variables in risk assessment.
Monte Carlo methods in risk assessment are finding increasingly widespread application. With the recognition that inputs may be correlated, the incorporation of such correlations into the simulation has become important. Most implementations rely upon the method of Iman and Conover for generating correlated random variables. In this work, alternative methods using copulas are presented for deriving correlated random variables. It is further shown that the particular algorithm or assumption used may have a substantial effect on the output results, due to differences in higher order bivariate moments.


[Chronic hepatitis: the etiological spectrum. The implications for treatment].
The prevalence of chronic hepatitis and its different aetiologies was studied in all patients above 10 years of age seen in the specialised outpatient clinic of our hospital over a 3 year period. Defining chronic hepatitis as a persistent elevation of the transaminases, 988 patients (62% of all the patients observed) were classified as follows: viral aetiology in 82%, metabolic in 2%, biliary in 2%, alcoholic in 11%, autoimmune in 1.5% and idiopathic in 2%. Among the viral group, hepatitis B virus infection was predominant (65%), followed by hepatitis C virus (26%) and delta hepatitis (8%). While the hepatitis C and delta patients presented high transaminases, in the HBsAg carriers this occurred in 94% and 20% of the HBeAg and anti-HBe-positive patients, respectively. Thirty per cent of the patients with chronic hepatitis B, 35% of those with chronic hepatitis C and 18% with delta hepatitis were selected for alpha interferon therapy. This demonstrated that in a significant proportion of patients with chronic viral hepatitis, therapy with interferon is not indicated. Corroborating other studies, with even stronger data, our study shows that viral aetiology is the most frequent type of chronic hepatitis.


Maternal emotion socialization in early childhood predicts adolescents' amygdala-vmPFC functional connectivity to emotion faces.
Guided by Eisenberg, Cumberland, and Spinrad's (1998) conceptual framework, we examined multiple components of maternal emotion socialization (i.e., reactions to children's negative emotion, emotion talk, emotional expressiveness) at 33 months of age as predictors of adolescents' amygdala-vmPFC connectivity and amygdala activation when labeling and passively observing angry and happy faces. For angry faces, more positive maternal emotion socialization behaviors predicted (a) less positive amygdala-vmPFC connectivity, which may reflect more mature vmPFC downregulation of the amygdala activation underlying implicit emotion regulation, and (b) more amygdala activation, which may reflect higher sensitivity to others' emotional cues. Associations between negative emotion socialization behaviors and neural responses to angry faces were nonsignificant, and findings for the models predicting neural responses to happy faces showed a less consistent pattern. By expanding Eisenberg et al.'s (1998) framework to consider neural processing of negative emotions, the current findings point toward the potential long-term implications of positive emotion socialization experiences during early childhood for optimal functioning of the amygdala-vmPFC circuitry during adolescence. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Advanced NSCLC patients with high IL-6 levels have altered peripheral T cell population and signaling.
High levels of circulating interleukin-6 (IL-6) are associated with a poor prognosis in many types of cancer including non-small cell lung cancer (NSCLC). While the inflammatory cytokine can stimulate the immune system and promote tumor growth, it remains unclear how circulating IL-6 can potentiate a poor prognosis. We hypothesized that a mechanism for IL-6-associated poor prognosis is that these patients would have altered T-cell populations and impaired T-cell signaling. Plasma levels of IL-6 were measured using a Cytometric Bead Array. T-cell populations from Non-small cell lung cancer patients were characterized using surface markers by flow cytometry, and signaling in the T-cell populations were measured by PhosFlow cytometry. We determine that patients with high circulating IL-6 levels had distinct T cell characteristics relative to those with low levels. Patients with high levels of IL-6 had significantly more Treg cells and elevated Programmed cell death protein-1 (PD-1) expression on CD4+, CD8+, Treg, and Th17 cells. These patients also showed impaired signal transducer and activator of transcription-1 (STAT1) signaling upon stimulation with IL-6 and phorbol 12-myristate 13-acetate (PMA), and T-Cells from a healthy donor that were treated for four days with IL-6 displayed a similar muting of STAT signaling, which verified the effect seen in patient samples. This work directly links circulating IL-6 with other poor prognostic indicators, STAT1 and PD-1, and highlights the effects of circulating IL-6 on the immune system. Our data suggest that alteration in T cell populations and function may be a mechanism underlying the poor prognosis seen in NSCLC patients with high IL-6 levels.


Clinical outcomes and mortality in peritoneal dialysis patients: a 10-year retrospective analysis in a single center.
To evaluate the clinical outcome, identify predictors of patient and technique survival in our peritoneal dialysis (PD) patients in the western region of Turkey. We included all patients who initiated therapy between 2001 and 2010. Socio-demographic characteristics such as who helped to administer the PD as well as conditions under which PD was chosen by patients were investigated from patients' files. Hemodialysis (HD) history and duration, additional systemic diseases, and end-stage renal disease etiologies of all patients were recorded. Clinical data such as blood pressure, amount of ultrafiltration, and laboratory parameters were evaluated before initiation of PD and during the last monitoring period. Infectious complications and their incidences were investigated. Patient and technique survival were investigated for every patient. 322 patients started PD treatment during the study period. 23 patients were excluded. Data from the remaining 299 patients (167 female, mean follow-up time 38.5 ± 26.8 months, mean age 44.7 ± 15.9 years) were evaluated retrospectively. It was determined that 87.3% of the patients made their PD exchanges without help from anyone. 79.9% of patients chose PD as their personal preference. 48 patients had HD history before PD. Peritonitis incidences and catheter exit site/tunnel infection attacks were 27 ± 23 and 32.3 ± 24.9 patient-months, respectively. During the follow-up period, 199 patients (80 patients transferred to HD, 78 patients died and, 41 patients had transplantation) were withdrawn from PD. The most frequent causes of death were cardiovascular events and peritonitis and/or sepsis, whereas most frequent causes of transfer to HD were peritonitis and/or sepsis. Mean survival time was 49.9 ± 2.6 months. The estimation of survival rate was 85.2%, 66.5% and 45.3% at 1, 3, and 5 years, respectively. Preference for PD (RR: 4.77, p < 0.001), presence of HD history (RR: 2.08, p = 0.04), presence of diabetes mellitus (RR: 2.13, p = 0.01), low pretreatment serum albumin (RR: 0.32, p < 0.001), and low serum parathormone levels at last visit (RR: 0.99, p = 0.04) were predictors of mortality. Mean technique survival duration was 48.5 ± 2.4 months. The estimation of technique survival by Kaplan-Meier analyses was 92%, 67% and 43% at 1, 3, and 5 years, respectively. Technique survival was associated with preference for PD (RR: 0.45, p < 0.001), presence of diabetes mellitus (RR: 1.92, p = 0.003), and pretreatment serum albumin levels (RR: 0.58, p = 0.003). Patient survival in the presented institute is similar to that reported in Western countries. Compulsory choice of PD, presence of HD history, presence of diabetes, low pretreatment serum albuminm, and low serum parathormone levels at last visit were the strongest predictors of death. Risk factors for technique failure were compulsory choice of PD, presence of diabetes, low pretreatment serum albumin.


Risk factors for fecal shedding of Salmonella in 91 US dairy herds in 1996.
In 1996, data on management practices used on US dairy operations were collected and analyzed for association with fecal shedding of Salmonella by dairy cows. A total of 4299 fecal samples from 91 herds was cultured for Salmonella isolation. Herd-size (adjusted odds ratios (OR) = 5.8, 95% CI 1.1, 31.3), region (OR = 5.7, CI 1.4, 23.5), use of flush water systems (OR = 3.5, CI 0.9, 14.7), and feeding brewers' products to lactating cows (OR = 3.4, CI 0.9, 12.9) were identified as the most important predictive risk factors. The population attributable risks (PARs) for herd-size, region, flush water system, and feeding brewers' products to lactating cows were 0.76, 0.46, 0.37, and 0.42, respectively. The estimated PAR for all four risk factors combined was 0.95. The effects of these factors need to be more-closely evaluated in more-controlled studies, in order to develop intervention programs that reduce Salmonella shedding.


The molecular structure and charge distribution of phorbol: parent compound of the tumor promoting phorbol diesters.
The geometry of phorbol, parent compound of the very highly active tumor promoting phorbol diesters, was totally optimized starting from the crystal structure of phorbol-5-bromofuroate-chloroform solvate (Petterson et al., J. Chem. Soc. B980, 1968). The full optimization of all atomic positions was done quantum chemically using the MINDO/3 potential energy surface and a modified Davidon-Fletcher-Powell search for local minima. The molecular structure and details of the electronic charge distribution are presented.


Authenticity of the traditional cypriot spirit "zivania" on the basis of 1h NMR spectroscopy diagnostic parameters and statistical analysis.
A previous publication (Kokkinofta et al. J. Agric. Food Chem. 2003, 51, 6233-6239) discussed the use of inductively coupled plasma spectroscopy to differentiate between the traditional Cypriot alcoholic beverage zivania and other spirits similar in alcoholic content collected from different countries. In the present paper (1)H NMR spectroscopy is applied to confirm the previous conclusions and to obtain additional physical-chemical characteristics that may be used to differentiate zivania from other similar beverages. NMR spectroscopy gave a satisfactory degree of prediction and classification between zivanias and other distillings. The validity of quantification of the method was tested using comparative GC data. It appears that chemical analysis can be very helpful for identifying the unique geological and climatic conditions existing in the island of Cyprus that lead to an authentic product.


Effect of isotonic exercise training on left ventricular volume during upright exercise.
To determine the changes in left ventricular volume and their time course during exercise we studied 30 runners. Left ventricular end-diastolic and end-systolic volumes were measured from biapical two-dimensional echocardiograms recorded during graded upright bicycle exercise. The validity of this echocardiographic technique was assessed by comparing measurements at rest and exercise with results obtained by gated equilibrium radionuclide angiography in 10 patients with coronary artery disease. Although the absolute volume measurements were lower by echocardiography, ejection fraction was not significantly different and the directional changes in volume during exercise were comparable. In the runners, resting left ventricular end-diastolic volume measurements by echocardiography correlated with their maximum bicycle exercise endurance times (r = .80). Left ventricular end-diastolic volume, stroke volume, and ejection fraction increased during exercise with the most marked changes occurring in the first half of exercise. Systolic blood pressure/end-systolic volume (SBP/ESV) also increased during exercise, but the largest change occurred during the second half of exercise. Left ventricular volumes were larger in the 12 competitive marathon runners (maximum exercise duration greater than or equal to 27 min) as compared with the 18 noncompetitive runners (exercise duration less than or equal to 23 min): resting end-diastolic volume 130 +/- 29 (SD) ml vs 87 +/- 20 ml (p less than .001), respectively. During exercise the competitive runners exhibited a larger increase in end-diastolic volume and the noncompetitive athletes showed a greater increase in SBP/ESV. Therefore, highly trained competitive marathon runners make greater use of the less energy-consuming Frank-Starling mechanism to accomplish high levels of isotonic exercise performance as compared with less well-trained runners.


A qualitative method for prediction of amine oxidation in methanol and water.
We have developed a predictive method, based on quantum chemical calculations, that qualitatively predicts N-oxidation by hydrogen peroxides in drug structures. The method uses linear correlations of two complementary approaches to estimate the activation barrier without calculating it explicitly. This method can therefore be automated as it avoids demanding transition state calculations. As such, it may be used by chemists without experience in molecular modeling and provide additional understanding to experimental findings. The predictive method gives relative rates for N,N-dimethylbenzylamine and N-methylmorpholine in good agreement with experiments. In water, the experimental rate constants show that N,N-dimethylbenzylamine is oxidized three times faster than N-methylmorpholine and in methanol it is two times faster. The method suggests it to be two and five times faster, respectively. The method was also used to correlate experimental with predicted activation barriers, linear free-energy relationships, for a test set of tertiary amines. A correlation coefficient R(2) = 0.74 was obtained, where internal diagnostics in the method itself allowed identification of outliers. The method was applied to four drugs: caffeine, azelastine, buspirone, and clomipramine, all possessing several nitrogens. Both overall susceptibility and selectivity of oxidation were predicted, and verified by experiments.


Sewage sludge and waterworks sludge stabilization in sludge treatment reed bed systems.
In this study, results about sludge stabilization in sludge treatment reed bed (STRB) systems in two different systems, Hanningfield STRB 1 (England), treating waterworks sludge, and Stenlille STRB 2 (Denmark), treating surplus activated sludge, are presented. The study mainly focused on the effectiveness of the STRBs systems in stabilizing sludge organic matter; in fact, parameters correlated to biochemical and chemico-structural properties of organic sludge matter were determined. Dewatering and sludge stabilization were effective in both STRBs, as highlighted by total and volatile dry solids trend. β-glucosidase, phosphatase, arylsulphatase, leucine amino-peptidase and butyrate esterase activities, enzymes related to C, P, S, N and overall microbial activity, respectively, significantly declined along the profile in both STRBs. The determination of humic carbon highlighted the formation of a stable nucleus of humified organic matter in both STRBs in the deepest layers, thus meaning the successful stabilization of sludge organic matter for both kind of sludges. Similar conclusions can be drawn from pyrolysis gas chromatography analysis (Py-GC), which enables the characterization of soil organic matter quality from a chemical-structural point of view. The pyrolytic indices of mineralization and humification showed that in both STRBs the sludge organic matter is well stabilized.


The theory of planned behaviour: self-identity, social identity and group norms.
The aim of the present study was to examine further the role that self-identity plays in the theory of planned behaviour and, more specifically, to: (1) examine the combined effects of self-identity and social identity constructs on intention and behaviour, and (2) examine the effects of self-identity as a function of past experience of performing the behaviour. The study was concerned with the prediction of intention to engage in household recycling and reported recycling behaviour. A sample of 143 community residents participated in the study. It was prospective in design: measures of the predictors and intention were obtained at the first wave of data collection, whereas behaviour was assessed two weeks later. Self-identity significantly predicted behavioural intention, a relationship that was not dependent on the extent to which the behaviour had been performed in the past. As expected, there was also evidence that the perceived norm of a behaviourally relevant reference group was related to behavioural intention, but only for participants who identified strongly with the group, whereas the relationship between perceived behavioural control (a personal factor) and intention was strongest for low identifiers.


Computer analyses of complete genomes suggest that some archaebacteria employ both eukaryotic and eubacterial mechanisms in translation initiation.
The translation initiation mechanism of archaebacteria is still not clearly understood. Our previous work showed that ATG triplets before start codons have been strongly depleted in eukaryotic genomes, presumably because ribosome of eukaryotes scans mRNA from the 5' to 3' direction to find proper start codons. Extra ATG triplets before start codons would confuse the process and thus they have been negatively selected in eukaryotic genomes. In eubacterial genomes, on the other hand, ribosome binds to the Shine-Dalgarno (SD) sequence at once without mRNA scanning, and the characteristic patterns of ATG triplet depletion were not observed (Saito, R., Tomita, M., 1999. On negative selection against ATG triplets near start codons in eukaryotic and procaryotic genomes. J. Mol. Evol. 48, 213-217). The ATG triplet analysis on archaebacterial genomes revealed that Methanococcus jannaschii and Pyrococcus horikoshii show patterns similar to eukaryotes, implying that these species employ scanning of mRNA from the 5' to 3' direction in the process of translation initiation. On the other hand, our earlier study found that these archaea have SD-like sequences, which are complementary to the 3' end sequence of 16S rRNA, as in eubacterial translation initiation (Osada, Y., Saito, R., Tomita, M. Analysis of base-pairing potentials between 16S rRNA and 5' UTR for translation initiation in various procaryotes. Bioinformatics, in press). These two results combined lead us to conclude that these archaea probably use a hybrid mechanism; their ribosome scans mRNAs from the 5' to 3' direction and then 16S rRNA binds to the SD-like sequence of the 5' UTR.


Successful treatment of Rhodococcus lung abscess and empyema thoracis in a heart transplant recipient.
Rhodococcosis is an uncommon cause of pulmonary infection in thoracic organ transplant recipients. We describe a heart transplant recipient diagnosed with Rhodococcus equi left upper lung abscess with empyema thoracis complicated by bacteremia. The patient was successfully treated with appropriate antibiotics, adequate surgical resection, and optimization of immunosuppressants.


Sequence-Based Deterministic Initialization for Evolutionary Algorithms.
It is well known that the performances of evolutionary algorithms are influenced by the quality of their initial populations. Over the years, many different techniques for generating an initial population by uniformly covering as much of the search space as possible have been proposed. However, none of these approaches considers any input from the function that must be evolved using that population. In this paper, a new initialization technique, which can be considered a heuristic space-filling approach, based on both function to be optimized and search space, is proposed. It was tested on two well-known unconstrained sets of benchmark problems using several computational intelligence algorithms. The results obtained reflected its benefits as the performances of all these algorithms were significantly improved compared with those of the same algorithms with currently available initialization techniques. The new technique also proved its capability to provide useful information about the function's behavior and, for some test problems, the initial population produced high-quality solutions. This method was also tested on a few multiobjective problems, with the results demonstrating its benefits.


Immunoglobulins and dietary protein antibodies in childhood coeliac disease.
Twenty-four children with coeliac disease were compared with a control group, comprising 17 children with a variety of gastroenterological disorders, with respect to serum immunoglobulins and dietary protein antibodies. Elevated levels of IgA and abnormally low levels of IgM were demonstrated in one third of the coeliac patients. Antibodies to at least one of eight dietary proteins were found in 50% of coeliac children. Three children with raised levels of serum IgA and two with deficient IgM were re-examined after varying periods on a gluten-free diet. Antibodies to dietary proteins had waned and immunoglobulin levels returned to normal in all cases. The raised IgA was considered to have resulted from an extensive immunological response to antigens of dietary origin which had entered through the abnormal gut mucosa. It is suggested that IgM deficiency was due to specific inhibition of IgM synthesis by dietary components which had also entered through the mucosa.


The intracellular localization of APE1/Ref-1: more than a passive phenomenon?
Human apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a perfect paradigm of the functional complexity of a biological macromolecule. First, it plays a crucial role, by both redox-dependent and -independent mechanisms, as a transcriptional coactivator for different transcription factors, either ubiquitous (i.e., AP-1, Egr-1, NF-kappaB, p53, HIF) or tissue-specific (i.e., PEBP-2, Pax-5 and -8, TTF-1), in controlling different cellular processes such as apoptosis, proliferation, and differentiation. Second, it acts, as an apurinic/apyrimidinic endonuclease, during the second step of the DNA base excision repair pathway, which is responsible for the repair of cellular alkylation and oxidative DNA damages. Third, it controls the intracellular reactive oxygen species production by negatively regulating the activity of the Ras-related GTPase Rac1. Despite these known functions of APE1/Ref-1, information is still scanty about the molecular mechanisms responsible for the coordinated control of its several activities. Some evidence suggests that the expression and subcellular localization of APE1/Ref-1 are finely tuned. APE1/Ref-1 is a ubiquitous protein, but its expression pattern differs according to the different cell types. APE1/Ref-1 subcellular localization is mainly nuclear, but cytoplasmic staining has also been reported, the latter being associated with mitochondria and/or presence within the endoplasmic reticulum. It is not by chance that both expression and subcellular localization are altered in several metabolic and proliferative disorders, such as in tumors and aging. Moreover, a fundamental role played by different posttranslational modifications in modulating APE1/Ref-1 functional activity is becoming evident. In the present review, we tried to put together a growing body of information concerning APE1/Ref-1's different functions, shedding new light on present and future directions to understand fully this unique molecule.


Activation of AMPK is essential for AICAR-induced glucose uptake by skeletal muscle but not adipocytes.
5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) reportedly activates AMP-activated protein kinase (AMPK) and stimulates glucose uptake by skeletal muscle cells. In this study, we investigated the role of AMPK in AICAR-induced glucose uptake by 3T3-L1 adipocytes and rat soleus muscle cells by overexpressing wild-type and dominant negative forms of the AMPKalpha2 subunit by use of adenovirus-mediated gene transfer. Overexpression of the dominant negative mutant had no effect on AICAR-induced glucose transport in adipocytes, although AMPK activation was almost completely abolished. This suggests that AICAR-induced glucose uptake by 3T3-L1 adipocytes is independent of AMPK activation. By contrast, overexpression of the dominant negative AMPKalpha2 mutant in muscle markedly suppressed both AICAR-induced glucose uptake and AMPK activation, although insulin-induced uptake was unaffected. Overexpression of the wild-type AMPKalpha2 subunit significantly increased AMPK activity in muscle but did not enhance glucose uptake. Thus, although AMPK activation may not, by itself, be sufficient to increase glucose transport, it appears essential for AICAR-induced glucose uptake in muscle.


A randomized equivalence trial comparing the efficacy and safety of Luffa comp.-Heel nasal spray with cromolyn sodium spray in the treatment of seasonal allergic rhinitis.
The objective of the clinical study was to investigate the efficacy and tolerance of a homeopathic nasal spray in cases of hay fever (seasonal allergic rhinitis) in comparison with the conventional intranasal cromolyn sodium therapy. In total, 146 outpatients with symptoms of hay fever were enrolled into the clinical study (randomized, double-blind, equivalence trial) (time of treatment: 42 days). The homeopathic remedy (Luffa comp.-Heel trade mark Nasal Spray, dosage: 0.14 ml per application, 4 times per a day / naris) consisted of a fixed combination made up of Luffa operculata, Galphimia glauca, histamine, and sulfur. The main outcome measure of the efficacy was the quality of life as measured by means of the Rhinoconjunctivitis Quality of Life-Questionnaire (RQLQ). The tolerance of the trial medication was registered by means of global assessment, rhinoscopy, recording of adverse events and with the aid of vital and laboratory parameters. The results of the study demonstrate a quick and lasting effect of the treatment. This effect was independent from the medication applied and produced a nearly complete remission of the hay fever symptoms. The RQLQ global score changed significantly in the course of the treatment, indicating therapeutic equivalence between the two forms of treatment. Adverse systemic effects did not occur. Local adverse events appeared in 3 patients. The study proved that, for the treatment of hay fever, the homeopathic nasal spray is as efficient and well tolerable as the conventional therapy with cromolyn sodium.


Specific detection of hepatitis C virus minus strand RNA in hematopoietic cells.
The presence of hepatitis C virus (HCV) negative strand RNA in extrahepatic compartments based on PCR detection assays has been suggested in many reports with a very heterologous detection rate (from 0 to 100%). In this study, we have analyzed the presence of HCV negative strand in hepatic (liver biopsies, n = 20) and extrahepatic (sera, n = 32; PBMC, n = 26 and fresh bone marrow cells, n = 8) compartments from infected patients with three different reverse transcriptase (RT)-PCR-based assays using primers located in the 5' noncoding region, with or without a tag selected to display different viral loads (10(5)-3 x 10(7) genomic equivalent/ml or gram) and viral genotypes (n = 5). Using synthetic as well as biological templates, we could document extensive artifactual detection of negative strand RNA, due to self priming and mispriming events, even either 5' noncoding region primer pair was used, whereas both artifacts were dramatically reduced (mispriming) or eliminated (selfpriming) using CAP-based RT-PCR assay. Mispriming artifacts were directly correlated to the titer of positive strand RNA present in the sample. Using the CAP-PCR assay, the presence of HCV negative strand RNA was found in 75% of livers (16:20) and only 8% of PBMC, independent of the genotype involved, but could not be documented in sera (0:32) and fresh bone marrow cells (0:6). These findings suggest that caution regarding the type of RT-PCR assay used and the level of HCV positive strand RNA present in the biological sample analyzed has to be taken to avoid false identification of viral reservoirs. The findings suggest that hematopoietic peripheral cells can support HCV replication, although in a very limited number of carriers.


Increasing silk fibre strength through heterogeneity of bundled fibrils.
Can naturally arising disorder in biological materials be beneficial? Materials scientists are continuously attempting to replicate the exemplary performance of materials such as spider silk, with detailed techniques and assembly procedures. At the same time, a spider does not precisely machine silk-imaging indicates that its fibrils are heterogeneous and irregular in cross section. While past investigations either focused on the building material (e.g. the molecular scale protein sequence and behaviour) or on the ultimate structural component (e.g. silk threads and spider webs), the bundled structure of fibrils that compose spider threads has been frequently overlooked. Herein, I exploit a molecular dynamics-based coarse-grain model to construct a fully three-dimensional fibril bundle, with a length on the order of micrometres. I probe the mechanical behaviour of bundled silk fibrils with variable density of heterogenic protrusions or globules, ranging from ideally homogeneous to a saturated distribution. Subject to stretching, the model indicates that cooperativity is enhanced by contact through low-force deformation and shear 'locking' between globules, increasing shear stress transfer by up to 200 per cent. In effect, introduction of a random and disordered structure can serve to improve mechanical performance. Moreover, addition of globules allows a tuning of free volume, and thus the wettability of silk (with implications for supercontraction). These findings support the ability of silk to maintain near-molecular-level strength at the scale of silk threads, and the mechanism could be easily adopted as a strategy for synthetic fibres.


Monophasic action potentials during induced hypothermia in hedgehog and guinea pig hearts.
To evaluate mechanisms behind the difference in susceptibility to ventricular fibrillation (VF) between the guinea pig and hedgehog heart, the cardiac electrophysiology of the two species was studied at normal body temperature and at different hypothermic levels by simultaneous recording of the monophasic action potential (MAP) and the external electrocardiogram (ECG). At normal body temperature, the duration of the ventricular MAP was significantly shorter in the hedgehog (93 +/- 8.1 ms) than in the guinea pig (138 +/- 2.6 ms). There was a distinct plateau phase in the guinea pig, whereas no such phase could be detected in the hedgehog. During hypothermia, a similar increase in MAP duration at full repolarization was noticed for both species. However, the prolongation of the MAP at lower repolarization levels was much less in the hedgehog. Besides, hypothermia-induced slow conduction and dispersion of ventricular repolarization was much more apparent in the guinea pig heart compared with the hedgehog heart. These differences may be important factors in the resistance to VF in the hedgehog, at normal body temperature and during hypothermia.


[Regulation of by arginine of cytochrome p-450 activity and lipid peroxidation in rat liver and testicular tissue during hypoxia].
Arginine, preadministered intraperitoneally at a dose of 120 mg per 100 g of body mass before hypoxia, decreased content of diene conjugates by 42-64% and Schiff bases by 7-15% in rat liver and testicular microsomal membranes as compared with control rats nontreated with arginine. Under these conditions cytochrome P-450 catalytic activity with aniline as a substrate was increased by 65-152% and with amidopyrine as a substrate--by 72-148%, respectively. Exogenous arginine inhibited an increase in membranes microviscosity, specific for hypoxic state; relative microviscosity of lipid bilayer was decreased by 36% and of the protein-lipid contact zones--by 84% as compared with control hypoxic animals.


HbA1c and FIB-4 as serologic markers for the risk of progression of stage A heart failure.
The use of glycosylated hemoglobin as a diabetic glycemic control and cardiovascular risk marker is well documented. It has also been suggested as a marker for early diastolic hemodynamic changes leading to clinical heart failure, but is less well characterized. This study explored the association between elevated glycosylated hemoglobin and liver Fibrosis-4 values and worsening measures of diastolic cardiac function in order to assess their potential as early serologic markers in cardiovascular disease prevention. A retrospective cohort analysis was conducted in 102 patients presenting to the Parkview Medical Center health system who had received a full resting echo characterized by normal systolic ejection fraction and clinical risk factors associated with stage A heart failure in conjunction with glycosylated hemoglobin and Fibrosis-4 scores within a 3-month time window. Using regression analysis, measures of diastolic cardiac function were assessed in conjunction with rising glycosylated hemoglobin levels characterized as <6.5 and >6.5 and Fibrosis-4 scores after controlling for the presence of hypertension, coronary artery disease and valvular heart disease. Glycosylated hemoglobin levels >6.5 were significantly associated with a higher E/e' ratio and closely associated with an elevated left atrial volume index both indicative of elevated left atrial pressure as a sensitive marker for diastolic cardiac dysfunction. Fibrosis-4 scores did not appear to be clinically associated with progression of diastolic dysfunction. Thus, glycosylated hemoglobin may act as an early marker for identifying patients at increased risk for the progression of stage A heart failure. Fibrosis-4 scores do not appear to be related.


Chemiluminescence-high-performance liquid chromatographic determination of tea catechin, (-)-epigallocatechin 3-gallate, at picomole levels in rat and human plasma.
A method of chemiluminescence detection-high-performance liquid chromatography (CL-HPLC) for the highly specific determination of tea catechin, (-)-epigallocatechin 3-gallate (EGCg), present in rat and human plasma has been newly developed. The CL-HPLC system consists of reversed-phase HPLC and chemiluminescence detector, in which separated EGCg generates chemiluminescence at post column successively reacting with the following two chemiluminescence cocktails; 8.2 M acetaldehyde in 50 mM phosphate buffer (pH 7.4, contained 108 mg horseradish peroxidase/L) and 8.8 M hydrogen peroxide aqueous solution. The plasma EGCg was extracted by methanol. This method enables the detection of EGCg in the free form selectively at as low as 2 pmol with recovery of 84%. The EGCg concentration in fasted rat plasma was initially below the detection limit (< 2 pmol/ml), but increased to maximum level (2284 pmol/ml plasma, 1047 ng/ml; calculated 0.012% of ingested EGCg) 30 min after a single oral supplementation of 56 mg EGCg per rat. The EGCg concentration in fasted human plasma was also initially below the detection limit and increased to 341 pmol/ml (156 ng/ml; calculated 0.32% of ingested EGCg) at 60 min after a single oral intake of 97 mg EGCg per subject. The results indicated that tea catechin, EGCg, is absorbed from the digestive tract into the rat and human body and that the CL-HPLC method reported here should be a powerful tool for studying the metabolic fate and bioavailability of EGCg.


A Vanadium(III) Complex with Blue and NIR-II Spin-Flip Luminescence in Solution.
Luminescence from Earth-abundant metal ions in solution at room temperature is a very challenging objective due to the intrinsically weak ligand field splitting of first-row transition metal ions, which leads to efficient nonradiative deactivation via metal-centered states. Only a handful of 3dn metal complexes (n ≠ 10) show sizable luminescence at room temperature. Luminescence in the near-infrared spectral region is even more difficult to achieve as further nonradiative pathways come into play. No Earth-abundant first-row transition metal complexes have displayed emission >1000 nm at room temperature in solution up to now. Here, we report the vanadium(III) complex mer-[V(ddpd)2][PF6]3 yielding phosphorescence around 1100 nm in valeronitrile glass at 77 K as well as at room temperature in acetonitrile with 1.8 × 10-4% quantum yield (ddpd = N,N'-dimethyl-N,N'-dipyridine-2-ylpyridine-2,6-diamine). In addition, mer-[V(ddpd)2][PF6]3 shows very strong blue fluorescence with 2% quantum yield in acetonitrile at room temperature. Our comprehensive study demonstrates that vanadium(III) complexes with d2 electron configuration constitute a new class of blue and NIR-II luminophores, which complement the classical established complexes of expensive precious metals and rare-earth elements.


Implications and emerging control strategies for ventilator-associated infections.
Ventilator-associated pneumonia (VAP) remains a major burden to the healthcare system and intubated patients in intensive care units. In fact, VAP is responsible for at least 50% of prescribed antibiotics to patients who need mechanical ventilation. One of the factors contributing to VAP pathogenesis is believed to be rapid colonization of biofilm-forming pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus on the surface of inserted endotracheal tubes. These biofilms serve as a protective environment for bacterial colonies and provide enhanced resistance towards many antibiotics. This review presents and discusses an overview of current strategies to inhibit the colonization and formation of biofilm on endotracheal tubes, including antibiotic treatment, surface modification and antimicrobial agent incorporation onto endotracheal tube materials.


Cationic or anionic sites? Selectivity optimization of ion-selective electrodes based on charged ionophores
The influence of ionic sites on the selectivities of ionophore-based ion-selective electrodes (ISEs) is described on the basis of a phase boundary potential model. The discussion presented here is significantly more general than previous ones. It is formulated for primary and interfering ions of any charges and it is valid for ISEs based on electrically charged or neutral ionophores. Furthermore, it also applies to membranes that contain more than one type of complex of the primary or interfering ion. It has been believed thus far that only ionic sites of the same charge sign as the primary ion improve the selectivities of ISEs based on charged ionophores. However, it is shown here that the charge sign of the ionic sites that give the highest potentiometric selectivities depends on the charge number of the primary and interfering ions and on the stoichiometry of their complexes with the ionophore. The validity of our model was confirmed experimentally with three ISEs based on different charged ionophores. ISEs based on lasalocid or 1-(N,N-dicyclohexylcarbamoyl)-2- (N,N-dioctadecylcarbamoyl)ethylphosphonic acid monomethyl ester (ETH 5639) as the ionophore responded selectively to Sr2+ or Mg2+, respectively, and discriminated well against other alkaline earth cations when their membranes contained anionic sites. These two electrodes are the first examples of ISEs based on charged ionophores for which maximum selectivities are obtained with membranes containing ionic sites with a charge sign opposite to that of the primary ion. On the other hand, the experimental F- selectivities of membranes based on oxo(5,10,15,20-tetraphenylporphyrinato)molybdenum-(V) improved gradually when the concentration of anionic sites was increased from 0 to 75 mol%. The selectivity-modifying influence of ionic sites for these three types of ISEs can be explained by considering the different stabilities of the 1:2 ion-ionophore complexes of the primary and of the interfering ions.


The Nordic Comparative Study on Sectorized Psychiatry: contact rates and use of services for patients with a functional psychosis.
As part of a Nordic comparative study on contact rates of new patients and use of services in seven catchment areas, contact rates and use of services for patients with a functional psychosis during a 1-year follow-up period were investigated. The highest contact rates were found in two large city catchment areas in Stockholm and Copenhagen. Compared to other patients in the cohorts, patients with a functional psychosis were more often found to be unemployed and living alone. They also showed more extensive service use in terms of both voluntary and compulsory admissions, and in the use of day-care facilities. In addition, they were more often multiple users of in-patient care (> or =3 admissions during the follow-up period). Large differences in service use among patients with a functional psychosis were discovered between the catchment areas, with the most extensive use of voluntary in-patient care and day-care facilities in Frederiksberg. Patients most frequently had compulsory admissions in Bodö and least frequently had them in Frederiksberg. Out-patient services were most frequently used in Stockholm. Correlations between levels of resources and use of services for patients with a functional psychosis were in general low, except for the rates of short-term beds, which showed a strong and significant correlation with the number of days in voluntary in-patient care (r=0.89).


Orbiter cloud photopolarimeter investigation.
The first polarization measurements of the orbiter cloud photopolarimeter have detected a planet-wide layer of submicrometer aerosols of substantial visible optical thickness, of the order of 0.05 to 0.1, in the lower stratosphere well above the main visible sulfuric acid cloud layer. Early images show a number of features observed by Mariner 10 in 1974, including planetary scale markings that propagate around the planet in the retrograde sense at roughly 100 meters per second and bright- and dark-rimmed cells suggesting convective activity at low latitudes. The polar regions are covered by bright clouds down to latitudes aproximately 50 degrees, with both caps significantly brighter (relative to low latitudes) than the south polar cloud observed by Mariner 10. The cellular features, often organized into clusters with large horizontal scale, exist also at mid-latitudes, and include at least one case in which a cell cuts across the edge of the bright polar cloud of the northern hemisphere.


Total Small Vessel Disease Score in Neurologically Healthy Japanese Adults in the Kashima Scan Study.
Objective We explored the association between the total small vessel disease (SVD) score obtained with magnetic resonance imaging and risk factors and outcomes in the Japanese population. Methods The presence of SVD features, including lacunes, cerebral microbleeds, white matter changes, and basal ganglia perivascular spaces on MRI, was summed to obtain a "total SVD score" (range 0-4). Ordinal and multinomial logistic regression analyses were performed to investigate the association of higher total SVD scores with vascular risk factors, the Mini-Mental State Examination (MMSE) score, and cerebral atrophy. Results We included 1,451 neurologically healthy adults (mean age, 57.1 years; 47% male). A multivariate ordinal logistic regression analysis showed that the total SVD score was associated with aging, hypertension, blood pressure (BP), diabetes mellitus, MMSE score, and deep cerebral atrophy, but the equal slopes assumption between scores did not hold. A multivariate multinomial logistic regression analysis (total SVD score 0=reference) showed that aging, hypertension, and BP were positively associated with scores of 1, 2, or ≥3. These effects, presented as odds ratios (ORs), increased as the score increased and were strongest with a score of ≥3 [aging (per 10-year increment), OR 4.00, 95% confidence interval (CI) 2.47-6.46; hypertension, OR 5.68, 95% CI 2.52-12.80; systolic BP (per standard deviation increase), OR 1.96, 95% CI 1.41-2.74, respectively]. Diabetes mellitus and deep cerebral atrophy tended to be associated with the SVD scores. The MMSE score showed no consistent associations. Conclusion The total SVD score may be a promising tool for indexing SVD, even in the Japanese population.


Stage at diagnosis of cancer varies with the age of the patient.
The stage of a cancer at diagnosis is multiply determined, theoretically depending on such disparate factors as tumor biology, patient education, and physician behaviors. Data from all Hispanic and non-Hispanic white residents of New Mexico diagnosed with a malignancy from 1969 through 1982 were analyzed to determine the relationship between the age of the patient and the stage of cancer at the time of diagnosis. Three general patterns were apparent. For cancers of the bladder, breast, cervix, ovary, thyroid, and uterus, and for melanoma, there were significant linear trends for the cancers to be diagnosed at more advanced stages in older patients. For cancers of the lung, pancreas, rectum, and stomach, there were significant linear trends for cancers to be diagnosed at an earlier stage in older patients. For cancers of the colon, kidney, liver, and prostate, there were no significant linear trends in stage at diagnosis versus age of the patient.


Tumor necrosis factor alpha-induced desumoylation and cytoplasmic translocation of homeodomain-interacting protein kinase 1 are critical for apoptosis signal-regulating kinase 1-JNK/p38 activation.
The apoptosis signal-regulating kinase 1 (ASK1)-JNK/p38 signaling pathway is pivotal component in cell apoptosis and can be activated by a variety of death stimuli including tumor necrosis factor (TNF) alpha and oxidative stress (reactive oxygen species). However, the mechanism for ASK1 activation is not fully understood. We have recently identified ASK1-interacting protein (AIP1) as novel signal transducer in TNFalpha-induced ASK1 activation by facilitating dissociation of ASK1 from its inhibitor 14-3-3. In the present study, we employed yeast two-hybrid system using the N-terminal domain of AIP1 as bait and identified homeodomain-interacting protein kinase 1 (HIPK1) as an AIP1-associated protein. Interestingly, we showed that TNFalpha induced HIPK1 desumoylation concomitant with a translocation from nucleus to cytoplasm at 15 min followed by a return to nucleus by 60 min. The kinetics of HIPK1 translocation correlates with those of stress-induced ASK1-JNK/P38 activation. A specific JNK inhibitor blocked the reverse but not the initial translocation of HIPK1, suggesting that the initial translocation is an upstream event of ASK1-JNK/p38 signaling and JNK activation regulates the reverse translocation as a feedback mechanism. Consistently, expression of HIPK1 increased, whereas expression of a kinase-inactive form (HIPK1-D315N) or small interference RNA of HIPK1 decreased stress-induced ASK1-JNK/P38 activation without effects on IKK-NF-kappaB signaling. Moreover, a sumoylation-defective mutant of HIPK1 (KR5) localizes to the cytoplasm and is constitutively active in ASK1-JNK/P38 activation. Furthermore, HIPK1-KR5 induces dissociation of ASK1 from its inhibitors 14-3-3 and thioredoxin and synergizes with AIP1 to induce ASK1 activation. Our study suggests that TNFalpha-induced desumoylation and cytoplasmic translocation of HIPK1 are critical in TNFalpha-induced ASK1-JNK/p38 activation.