Early diagnosis of acute myocardial infarction in the elderly using more sensitive cardiac troponin assays.
To examine the diagnostic accuracy of sensitive cardiac troponin (cTn) assays in elderly patients, since elevated levels with sensitive cTn assays were reported in 20% of elderly patients without acute myocardial infarction (AMI). In this multi-centre study, we included 1098 consecutive patients presenting with symptoms suggestive of AMI, 406 (37%) were >70 years old. Measurement of three investigational sensitive cTn assays [Roche high-sensitive cTnT (hs-cTnT), Siemens cTnI-Ultra, and Abbott-Architect cTnI) and the standard assay (Roche cTnT) was performed in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists. Acute myocardial infarction was the adjudicated final diagnosis in 24% of elderly patients. Among elderly patients without AMI, baseline cTn levels were elevated above the 99th percentile in 51% with Roche hs-cTnT, in 17% with Siemens TnI-Ultra, and 13% with Abbott-Architect cTnI. The diagnostic accuracy as quantified by the area under the receiver operating characteristic (ROC) curve (AUC) was significantly greater for the sensitive cTn assays compared with the standard assay (AUC for Roche hs-cTnT, 0.94; Siemens cTnI-Ultra, 0.95; and Abbott-Architect cTnI, 0.95 vs. AUC for the standard assay, 0.90; P < 0.05 for comparisons). The best cut-offs for the sensitive cTn-assays determined by the ROC-curve in elderly patients differed clearly from those in younger patients. Furthermore, the prognostic value regarding 90-day mortality varied among the sensitive cTn assays. Sensitive cTn assays have high diagnostic accuracy also in the elderly. Mild elevations are common in elderly non-AMI patients, therefore the optimal cut-off levels are substantially higher in elderly as compared with younger patients. Furthermore, sensitive cTn assays yielded different prognostic value.


Improved survival of cardiac transplantation candidates with implantable cardioverter defibrillator therapy: role of beta-blocker or amiodarone treatment.
Survival in patients awaiting cardiac transplantation is poor due to the severity of left ventricular dysfunction and the susceptibility to ventricular arrhythmia. The potential role of implantable cardioverter defibrillators (ICDs) in this group of patients has been the subject of increasing interest. The aims of this study were to ascertain whether ICDs improve the survival rate of patients on the waiting list for cardiac transplantation and whether any improvement is independent of concomitant beta-blocker or amiodarone therapy. Data comprised findings from 310 consecutive patients at a single center who were evaluated and deemed suitable for cardiac transplantation and placed on the waiting list. Kaplan-Meier actuarial approach was used for survival analysis. Survival analysis censored patients at time of transplantation or death. Of the 310 patients, 111 (35.8%) underwent successful cardiac transplantation and 164 (52.9%) died while waiting; 35 patients remain on the waiting list. Fifty-nine (19%) patients had ICD placement for ventricular arrhythmias prior to or after being listed. Twenty-nine (49.1%) ICD patients survived until cardiac transplantation, 13 (22%) patients died, and 17 (28.8%) remain on the waiting list. Among non-ICD patients, 82 (32.7%) received transplants, 151 (60.2%) died, and 18 (7.2%) remain on the waiting list. Survival rates at 6 months and 1, 2, 3, and 4 years were better for all ICD patients compared to non-ICD patients (log-rank x2, P = 0.0001). By multivariate analysis, ICD therapy and beta-blocker treatment were the strongest predictors of survival. Further, ICD treatment was associated with improved survival independent of concomitant treatment with beta-blocker or amiodarone. Among ICD and non-ICD patients treated with a beta-blocker or amiodarone, survivals at the 1 and 4 years were 93% vs 69% and 57% vs 32%, respectively (log-rank x2, P = 0.003). ICD therapy is associated with improved survival in high-risk cardiac transplant candidates, and ICD benefit appears to be independent of concomitant treatment.


Use of a glutaric acid cocrystal to improve oral bioavailability of a low solubility API.
The bioavailability of a development candidate active pharmaceutical ingredient (API) was very low after oral dosing in dogs. In order to improve bioavailability, we sought to increase the dissolution rate of the solid form of the API. When traditional methods of forming salts and amorphous material failed to produce a viable solid form for continued development, we turned to the non-traditional approach of cocrystallization. A crystal engineering approach was used to design and execute a cocrystal screen of the API. Hydrogen bonding between the API and pharmaceutically acceptable carboxylic acids was identified as a viable synthon for associating multiple components in the solid state. A number of carboxylic acid guest molecules were tested for cocrystal formation with the API. A cocrystal containing the API and glutaric acid in a 1:1 molecular ratio was identified and the single crystal structure is reported. Physical characterization of the cocrystal showed that it is unique regarding thermal, spectroscopic, X-ray, and dissolution properties. The cocrystal solid is nonhygroscopic, and chemically and physically stable to thermal stress. Use of the cocrystal increased the aqueous dissolution rate by 18 times as compared to the homomeric crystalline form of the drug. Single dose dog exposure studies confirmed that the cocrystal increased plasma AUC values by three times at two different dose levels. APIs that are non-ionizable or demonstrate poor salt forming ability traditionally present few opportunities for creating crystalline solid forms with desired physical properties. Cocrystals are an additional class of crystalline solid that can provide options for improved properties. In this case, a crystalline molecular complex of glutaric acid and an API was identified and used to demonstrate an improvement in the oral bioavailability of the API in dogs.


A different recruitment of the lateral and basolateral amygdala promotes contextual or elemental conditioned association in Pavlovian fear conditioning.
Convergent data suggest dissociated roles for the lateral (LA) and basolateral (BLA) amygdaloid nuclei in fear conditioning, depending on whether a discrete conditioned stimulus (CS)-unconditional stimulus (US) or context-US association is considered. Here, we show that pretraining inactivation of the BLA selectively impaired conditioning to context. In contrast, inactivation of the LA disrupted conditioning to the discrete tone CS, but also either impaired or enhanced contextual conditioning, depending on whether the context was in the foreground or in the background. Hence, these findings refine the current model of the amygdala function in emotional learning by showing that the BLA and the LA not only differentially contribute to elemental and context-US association, but also promote, through their interaction, the most relevant of these two associations.


Ralstonia solanacearum effector RipAK suppresses homodimerization of the host transcription factor ERF098 to enhance susceptibility and the sensitivity of pepper plants to dehydration.
Plants have evolved a sophisticated immune system to defend against invasion by pathogens. In response, pathogens deploy copious effectors to evade the immune responses. However, the molecular mechanisms used by pathogen effectors to suppress plant immunity remain unclear. Herein, we report that an effector secreted by Ralstonia solanacearum, RipAK, modulates the transcriptional activity of the ethylene-responsive factor ERF098 to suppress immunity and dehydration tolerance, which causes bacterial wilt in pepper (Capsicum annuum L.) plants. Silencing ERF098 enhances the resistance of pepper plants to R. solanacearum infection not only by inhibiting the host colonization of R. solanacearum but also by increasing the immunity and tolerance of pepper plants to dehydration and including the closure of stomata to reduce the loss of water in an abscisic acid signal-dependent manner. In contrast, the ectopic expression of ERF098 in Nicotiana benthamiana enhances wilt disease. We also show that RipAK targets and inhibits the ERF098 homodimerization to repress the expression of salicylic acid-dependent PR1 and dehydration tolerance-related OSR1 and OSM1 by cis-elements in their promoters. Taken together, our study reveals a regulatory mechanism used by the R. solanacearum effector RipAK to increase virulence by specifically inhibiting the homodimerization of ERF098 and reprogramming the transcription of PR1, OSR1, and OSM1 to boost susceptibility and dehydration sensitivity. Thus, our study sheds light on a previously unidentified strategy by which a pathogen simultaneously suppresses plant immunity and tolerance to dehydration by secreting an effector to interfere with the activity of a transcription factor and manipulate plant transcriptional programs.


Multicenter, prospective, randomized, single-blind study comparing the efficacy and gastrointestinal complications of early jejunal feeding with early gastric feeding in critically ill patients.
To compare the incidence of enteral nutrition-related gastrointestinal complications, the efficacy of diet administration, and the incidence of nosocomial pneumonia in patients fed in the stomach or in the jejunum. Prospective, randomized multicenter study. Intensive care units (ICUs) in 11 teaching hospitals. Critically ill patients who could receive early enteral nutrition more than 5 days. Enteral nutrition was started in the first 36 hrs after admission. One group was fed with a nasogastric tube (GEN group) and the other in the jejunum through a dual-lumen nasogastrojejunal tube (JEN group). Gastrointestinal complications were previously defined. The efficacy of diet administration was calculated using the volume ratio (expressed as the ratio between administered and prescribed volumes). Nosocomial pneumonia was defined according the Centers for Disease Control and Prevention's definitions. One hundred ten patients were included (GEN: 51, JEN: 50). Both groups were comparable in age, gender, Acute Physiology and Chronic Health Evaluation II, and Multiple Organ Dysfunction Score. There were no differences in feeding duration, ICU length of stay, or mortality (43% vs. 38%). The JEN group had lesser gastrointestinal complications (57% vs. 24%, p <.001), mainly because of a lesser incidence of increased gastric residuals (49% vs. 2%, p <.001). Volume ratio was similar in both groups. A post hoc analysis showed that the JEN group had a higher volume ratio at day 7 than the GEN group (68% vs. 82%, p <.03) in patients from ICUs with previous experience in jejunal feeding. Both groups had a similar incidence of nosocomial pneumonia (40% vs. 32%). Gastrointestinal complications are less frequent in ICU patients fed in the jejunum. Nevertheless, it seems to be a necessary learning curve to achieve better results with a postpyloric access. Early enteral nutrition using a nasojejunal route seems not to be an efficacious measure to decrease nosocomial pneumonia in critically ill patients.


Dietary factors in colon carcinogenesis with special emphasis on the role of dietary fat and dietary fibre.
Dietary factors other than fat and fibre have been reported to influence colon cancer risk, in particular a protective effect of cruciferous vegetables (Graham et al., 1978) and an increased risk associated with beer consumption (Breslow and Enstrom, 1974) have been suggested. The role of these dietary aspects is however less well understood than that of fat and fibre; for beer consumption the statistical association has been suggested to be a non-causal nature (Jensen, 1979; Jensen, 1982). In summary then the epidemiological pattern of colon cancer points to various aspects of diet as a determinant of colon cancer risk. If - as suggested - an imbalance between the intake of fat and fibre is of importance mediated by the fecal concentration of bile acids further studies should attempt to clarify the relative role of these two items in addition to shedding further light on the role of other dietary aspects, for which our present knowledge is even more incomplete. With a view to cancer prevention it may prove more productive to give priority to a search for items that have a protective effect. It may thus be more acceptable to high risk populations to add perhaps only a limited amount of "roughage" to their diets than to reduce the daily fat-intake.


Exosomal markers (CD63 and CD9) expression and their prognostic significance using immunohistochemistry in patients with pancreatic ductal adenocarcinoma.
Exosomes are important mediators of intercellular communications and play pivotal roles in cancer progression, metastasis and chemoresistance. CD63 and CD9 are widely accepted exosomal markers. In patients with pancreatic ductal adenocarcinoma (PDAC), positive correlation between CD9 expression and overall survival (OS) was reported. CD63 expression was conserved in all patients with no reported prognostic significance. This study explored the prognostic significance of CD63 and CD9 expression using immunohistochemistry (IHC) in patients with PDAC of mixed racial background. Between 2012 and 2016, 49 patients with PDAC had available tissues for CD63 and CD9 staining using IHC. Two pathologists independently scored the CD63 and CD9 expression. Staining intensity was graded from 1-3 and staining percentage was estimated in 10% increments. Mean Quick-score (Q-score) (Intensity X Percentage of staining) was calculated. The mean Q-score for CD63 and CD9 are higher in primary tumor from the pancreas compared to pancreatic tumor from metastatic sites (185 vs. 102, P=0.0002) and (48 vs. 20, P=0.0418) respectively. We fitted Cox proportion hazard regression models to investigate the impact of the covariates CD63 and CD9 on progression free survival (PFS) and OS. CD63 has significant impact on PFS (P=0.0135) and OS (P=0.003). The higher the CD63 Q-score, the longer the PFS and OS. CD9 doesn't have significant impact on PFS (P=0.5734) or OS (P=0.2682). The mean CD63 and CD9 Q-scores are slightly higher in African American (AA) compared to Caucasians (157 vs. 149, P=0.76) and (45 vs. 29, P=0.43) respectively. CD63 and CD9 expression is higher in primary tumor from the pancreas compared to pancreatic tumor from metastatic sites. There is correlation between CD63 expression (but not CD9 in this cohort) and PFS and OS. To our knowledge, this is the first study to show prognostic significance of CD63 expression in patients with PDAC using IHC. A trend of higher expression of CD63 and CD9 among AA compared to Caucasians was also noticed.


The Development of an International Oncofertility Competency Framework: A Model to Increase Oncofertility Implementation.
Despite international evidence about fertility preservation (FP), several barriers still prevent the implementation of equitable FP practice. Currently, oncofertility competencies do not exist. The aim of this study was to develop an oncofertility competency framework that defines the key components of oncofertility care, develops a model for prioritizing service development, and defines the roles that health care professionals (HCPs) play. A quantitative modified Delphi methodology was used to conduct two rounds of an electronic survey, querying and synthesizing opinions about statements regarding oncofertility care with HCPs and patient and family advocacy groups (PFAs) from 16 countries (12 high and 4 middle income). Statements included the roles of HCPs and priorities for service development care across ten domains (communication, oncofertility decision aids, age-appropriate care, referral pathways, documentation, oncofertility training, reproductive survivorship care and fertility-related psychosocial support, supportive care, and ethical frameworks) that represent 33 different elements of care. The first questionnaire was completed by 457 participants (332 HCPs and 125 PFAs). One hundred and thirty-eight participants completed the second questionnaire (122 HCPs and 16 PFAs). Consensus was agreed on 108 oncofertility competencies and the roles HCPs should play in oncofertility care. A three-tier service development model is proposed, with gradual implementation of different components of care. A total of 92.8% of the 108 agreed competencies also had agreement between high and middle income participants. FP guidelines establish best practice but do not consider the skills and requirements to implement these guidelines. The competency framework gives HCPs and services a structure for the training of HCPs and implementation of care, as well as defining a model for prioritizing oncofertility service development. Despite international evidence about fertility preservation (FP), several barriers still prevent the implementation of equitable FP practice. The competency framework gives 108 competencies that will allow health care professionals (HCPs) and services a structure for the development of oncofertility care, as well as define the role HCPs play to provide care and support. The framework also proposes a three-tier oncofertility service development model which prioritizes the development of components of oncofertility care into essential, enhanced, and expert services, giving clear recommendations for service development. The competency framework will enhance the implementation of FP guidelines, improving the equitable access to medical and psychological oncofertility care.


Differences in intestinal protein synthesis and cellular proliferation in well-nourished rats consuming conventional laboratory diets.
Male Wistar rats (100 g) were given a commercial pellet feed or a semi-synthetic diet ad lib. Although the pellet-fed group grew slightly faster than the other group during the early part of the feeding period, there was no significantly difference between the final weights of the groups. The fractional rates of protein synthesis in jejunum, proximal ileum and liver were measured by a technique based on the determination of L-[4-3H]phenylalanine incorporation over a short time period. Protein synthesis was higher in both jejunum and ileum of the pellet-fed rats compared with those eating the semi-synthetic diet, but there was no difference between the rates of protein synthesis measured in the livers of the groups. The rate of mucosal cell division was significantly faster in the ileal mucosa of the pellet-fed group compared with the other group, and there were significant differences in some aspects of mucosal morphology. The maintenance of higher rates of cell turnover and protein synthesis in animals given a commercial pellet feed is unexplained, but it may be related to the presence of non-absorbable polysaccharides or other complex plant materials in the pellet feed.


Aerosolized Medications for Gene and Peptide Therapy.
Inhalation therapy has matured to include drugs that: (1) deliver nucleic acids that either lead to the restoration of a gene construct or protein coding sequence in a population of cells or suppress or disrupt production of an abnormal gene product (gene therapy); (2) deliver peptides that target lung diseases such as asthma, sarcoidosis, pulmonary hypertension, and cystic fibrosis; and (3) deliver peptides to treat diseases outside the lung whose target is the systemic circulation (systemic drug delivery). These newer applications for aerosol therapy are the focus of this paper, and I discuss the status of each and the challenges that remain to their successful development. Drugs that are highlighted include: small interfering ribonucleic acid to treat lung cancer and Mycobacterium tuberculosis; vectors carrying the normal alpha-1 antitrypsin gene to treat alpha-1 antitrypsin deficiency; vectors carrying the normal cystic fibrosis transmembrane conductance regulator gene to treat cystic fibrosis; vasoactive intestinal peptide to treat asthma, pulmonary hypertension, and sarcoidosis; glutathione to treat cystic fibrosis; granulocyte-macrophage colony-stimulating factor to treat pulmonary alveolar proteinosis; calcitonin for postmenopausal osteoporosis; and insulin to treat diabetes. The success of these new aerosol applications will depend on many factors, such as: (1) developing gene therapy formulations that are safe for acute and chronic administrations to the lung, (2) improving the delivery of the genetic material beyond the airway mucus barrier and cell membrane and transferring the material to the cell cytoplasm or the cell nucleus, (3) developing aerosol devices that efficiently deliver genetic material and peptides to their lung targets over a short period of time, (4) developing devices that increase aerosol delivery to the lungs of infants, (5) optimizing the bioavailability of systemically delivered peptides, and (6) developing peptide formulations for systemic delivery that do not cause persistent cough or changes in lung function.


Top-down control of hippocampal signal-to-noise by prefrontal long-range inhibition.
Prefrontal cortex (PFC) is postulated to exert "top-down control" on information processing throughout the brain to promote specific behaviors. However, pathways mediating top-down control remain poorly understood. In particular, knowledge about direct prefrontal connections that might facilitate top-down control of hippocampal information processing remains sparse. Here we describe monosynaptic long-range GABAergic projections from PFC to hippocampus. These preferentially inhibit vasoactive intestinal polypeptide-expressing interneurons, which are known to disinhibit hippocampal microcircuits. Indeed, stimulating prefrontal-hippocampal GABAergic projections increases hippocampal feedforward inhibition and reduces hippocampal activity in vivo. The net effect of these actions is to specifically enhance the signal-to-noise ratio for hippocampal encoding of object locations and augment object-induced increases in spatial information. Correspondingly, activating or inhibiting these projections promotes or suppresses object exploration, respectively. Together, these results elucidate a top-down prefrontal pathway in which long-range GABAergic projections target disinhibitory microcircuits, thereby enhancing signals and network dynamics underlying exploratory behavior.


Composites of (NH2)-MIL-53(Al) and CBB as bifunctional electrocatalysts for overall electrochemical water splitting in all pH solutions.
Electrochemical water splitting is one of the most active areas of energy research, yet the benchmark electrocatalysts used for this area are based on expensive noble metals and transition metals, thus mainly reactions in alkaline solution. MOFs and halide perovskite are novel electrochemical catalysts but unstable in water basically. Here we report a study on composites of (NH2)-MIL-53(Al) MOFs and CBB halide perovskite (Cs3Bi2Br9), which exhibit obvious activity for overall electrochemical water splitting for long-term stability with little deactivation after 10 h in all pH solutions.


Acute in-vivo effects of adrenocorticotrophin on plasma levels of glucagon, insulin, glucose and free fatty acids in rabbits: involvement of the alpha-adrenergic nervous system.
Intravenous injection of 8.5 nmol (1-24)ACTH increased the plasma levels of glucagon, insulin, glucose and free fatty acids in rabbits. The (1-24)ACTH-induced hyperglucagonaemia and hyperinsulinaemia started 3 and 20 min after the injection respectively. Similar increases in the plasma levels of glucagon, insulin and free fatty acids were found with 5.3 nmol (1-39)ACTH, whereas (1-4)ACTH, (4-10)ACTH, (1-10)ACTH, (11-24)ACTH, (7-38)ACTH and (18-39)ACTH (corticotrophin-like intermediate lobe peptide) injected at doses of approximately 8 nmol were inactive. Infusions with the alpha-adrenergic blocking drug, phentolamine, reduced the (1-24) ACTH-induced hyperglucagonaemia and hyperglycaemia, and augmented the (1-24)ACTH-induced hyperinsulinaemia, which now became significant after 5 min. Infusions with the beta-adrenergic blocking drug, propranolol, did not diminish the (1-24)ACTH-induced effects, but killed the rabbits after 2-4 h. It is concluded that the acute in-vivo effects of ACTH in rabbits are modulated by the involvement of alpha-adrenergic receptors, which increased the plasma levels of glucagon and glucose, and delayed and diminished the ACTH-induced increases in the plasma levels of insulin. The (1-24)ACTH-induced increases in the plasma levels of free fatty acids were not influenced by the adrenergic blocking drugs.


Efficacy of bystander CPR: intervention by lay people and by health care professionals.
Early cardiopulmonary resuscitation (CPR) by bystanders prior to the arrival of the rescue team has been shown to be associated with increased survival after out-of-hospital cardiac arrest. The aim of this survey was to evaluate the impact on survival of no bystander CPR, lay bystander CPR and professional bystander CPR. Patients suffering an out-of-hospital cardiac arrest in Sweden between 1990 and 2002 who were given CPR and were not witnessed by the ambulance crew were included. In all, 29,711 patients were included, 36% of whom received bystander CPR prior to the arrival of the rescue team. Among the latter, 72% received CPR from lay people and 28% from professionals. Survival to 1 month was 2.2% among those who received no bystander CPR, 4.9% among those who received bystander CPR from lay people (p<0.0001) and 9.2% among those who received bystander CPR from professionals (p<0.0001 compared with bystander CPR by lay people). In a multivariate analysis, lay bystander CPR was associated with improved survival compared to no bystander CPR (OR: 2.04; 95% CI: 1.72-2.42), and professional bystander CPR was associated with improved survival compared to lay bystander CPR (OR: 1.37; 95% CI: 1.12-1.67). Among patients suffering an out-of-hospital cardiac arrest, bystander CPR by lay persons (excluding health care professionals) is associated with an increased chance of survival. Furthermore, there is a distinction between lay persons and health care providers; survival is higher when the latter perform bystander CPR. However, these results may not be explained by differences in the quality of CPR.


Description of a new species of myxozoan from Notropis hudsonius in the Great Lakes region of Canada.
Myxobolus burti n. sp. is described from striated muscle of Notropis hudsonius (Cyprinidae) collected from localities in Lake Superior, Lake Michigan, Lake Huron, Lake St. Claire, Lake Erie, Lake Ontario, and the St. Lawrence River. Myxobolus burti is intracellular, forming thin-walled, cigar-shaped plasmodia within striated muscle cells of the body. It exhibits disporoblastic, oval spores, approximately 10 µm long, 8 µm wide, and 6 µm thick, with a length-to-width ratio of 1.3 ∶ 1. They resemble most closely those of Myxobolus bellus Kudo, 1934, and Myxobolus mutabilis Kudo, 1934, but have polar capsules unequal in length (5.3 vs. 4.7 µm) and oblique filament coils. The new parasite was not encountered in routine examination of other small-bodied fishes at collection locations and thus looks to be specific to N. hudsonius. A comparative plate of similar species encountered during surveys of these fishes in the northeast is presented to contrast the uniqueness of the new species.


Repeated Electroconvulsive Shock Selectively Alters gamma-Aminobutyric Acid Levels in the Rat Brain: Effect of Electrode Placement.
The neurochemical mechanisms of electroconvulsive therapy (ECT) are not fully elucidated. We examined the effects of electroconvulsive shock (ECS) on brain gamma-aminobutyric acid (GABA) systems. Male Wistar-Furth rats were given ECS via auricular (ear-clip) or corneal electrodes once per day (120 V, 0.5 s) for 10 consecutive days. Two groups of sham ECS rats, one for auricular placement and one for corneal placement, served as controls. Current was measured and seizures were scored during each ECS trial. Rats receiving ECS via corneal electrodes were subjected to more electrical current compared to rats treated with auricular electrodes. Although both groups exhibited behavioral seizures of similar duration, electrode placement had a differential influence on the expression of tonic hindlimb extension and clonic hindlimb activity over the 10-day regimen. GABA levels were increased in all brain regions examined in rats treated with auricular electrodes except the hippocampus and nucleus accumbens; rats treated with corneal electrodes exhibited GABA increases in the hippocampus, frontal cortex, hypothalamus, and olfactory bulbs; a significant decrease in nucleus accumbens; and no change in the substantia nigra and striatum. The mode of ECS delivery selectively alters the pattern of regional alterations of brain GABA level induced by ECS. This effect may be a function of current intensity or localization.


Voltage-gated Ca2+ currents in rat gastric enterochromaffin-like cells.
Enterochromaffin-like (ECL) cells are histamine-containing endocrine cells in the gastric mucosa that maintain a negative membrane potential of about -50 mV, largely due to voltage-gated K+ currents [D. F. Loo, G. Sachs, and C. Prinz. Am. J. Physiol. 270 (Gastrointest Liver Physiol. 33): G739-G745, 1996]. The current study investigated the presence of voltage-gated Ca2+ channels in single ECL cells. ECL cells were isolated from rat fundic mucosa by elutriation, density gradient centrifugation, and primary culture to a purity > 90%. Voltage-gated Ca2+ currents were measured in single ECL cells using the whole cell configuration of the patch-clamp technique. Depolarization-activated currents were recorded in the presence of Na+ or K+ blocking solutions and addition of 20 mM extracellular Ca2+. ECL cells showed inward currents in response to voltage steps that were activated at a test potential of around -20 mV with maximal inward currents observed at +20 mV and 20 mM extracellular Ca2+. The inactivation rate of the current decreased with increasingly negative holding potentials and was totally abolished at a holding potential of -30 mV. Addition of extracellular 20 mM Ba2+ instead of 20 mM Ca2+ increased the depolarization-induced current and decreased the inactivation rate. The inward current was fully inhibited by the specific L-type Ca2+ channel inhibitor verapamil (0.2 mM) and was augmented by the L-type Ca2+ channel activator BAY K 8644 (0.07 mM). We conclude that depolarization activates high-voltage-activated Ca2+ channels in ECL cells. Activation characteristics, Ba2+ effects, and pharmacological results imply the presence of L-type Ca2+ channels, whereas inactivation kinetics suggest the presence of additional N-type channels in rat gastric ECL cells.


Kneeling ability after total knee replacement.
Kneeling ability is consistently the poorest patient-rated outcome after total knee replacement (TKR), with 60-80% of patients reporting difficulty kneeling or an inability to kneel.Difficulty kneeling impacts on many activities and areas of life, including activities of daily living, self-care, leisure and social activities, religious activities, employment and getting up after a fall. Given the wide range of activities that involve kneeling, and the expectation that this will be improved with surgery, problems kneeling after TKR are a source of dissatisfaction and disappointment for many patients.Research has found that there is no association between range of motion and self-reported kneeling ability. More research is needed to understand if and how surgical factors contribute to difficulty kneeling after TKR.Discrepancies between patients' self-reported ability to kneel and observed ability suggests that patients can kneel but elect not to. Reasons for this are multifactorial, including knee pain/discomfort, numbness, fear of harming the prosthesis, co-morbidities and recommendations from health professionals. There is currently no evidence that there is any clinical reason why patients should not kneel on their replaced knee, and reasons for not kneeling could be addressed through education and rehabilitation.There has been little research to evaluate the provision of healthcare services and interventions for patients who find kneeling problematic after TKR. Increased clinical awareness of this poor outcome and research to inform the provision of services is needed to improve patient care and allow patients to return to this important activity. Cite this article: EFORT Open Rev 2019;4:460-467. DOI: 10.1302/2058-5241.4.180085.


A survey on antibiotic usage in dairy herds in Pennsylvania.
A survey was conducted (July 2001 to June 2002) on antibiotic usage of 113 dairy herds from 13 counties in Pennsylvania. Fifty percent of dairy farms surveyed maintained antibiotic treatment records. Only 21% of dairy producers had written plans for treating sick animals. Thirty-two percent of dairy producers sought veterinarian advice before administering antibiotics and on most farms (93%), antibiotics were administered by the owner/manager or designated herdsman. Twenty-four percent of the dairy producers said they always completed the course of antibiotic treatment. Any extra-label use of antibiotics was administered only on the guidelines of a veterinarian on majority of the farms. Comprehensive records from 33 dairy farms indicated that antibiotic usage was largest for calves with enteritis (36%) followed by pneumonia in calves (25%) and foot rot in cattle (16%). Twenty-four antibiotics including beta-lactams, spectinomycin, florfenicol, and tetracyclines were used on these farms. Beta-lactam antibiotics were used mostly for dry cow therapy, clinical mastitis, and on some farms for pneumonia and metritis. On 18% of the dairy herds surveyed, ceftiofur was used in an extra-label manner to treat mastitis in lactating cattle. On 70% of farms, calves were fed medicated milk replacers containing oxytetracycline and neomycin. The results of this study suggest that antibiotics are used extensively on dairy herds for both therapeutic and prophylactic purposes. Beta-lactams and tetracyclines were the most widely used antibiotics. There is considerable variation in the management practices associated with antibiotic use on dairy farms. It is anticipated that the findings of this survey will permit developing new strategies for prudent use of antibiotics on dairy herds.


Cognitive-exercise dual-task attenuates chronic cerebral ischemia-induced cognitive impairment by activating cAMP/PKA pathway through inhibiting EphrinA3/EphA4.
The prevalence of vascular cognitive impairment induced by chronic cerebral ischemia (CCI) is increasing year by year. Cognitive-exercise dual-task intervention has shown beneficial effects on improving cognitive performance in ischemic patients. It is well known that the tyrosine kinase ligand-receptor (Ephrin-Eph) system plays an important role in synaptic transmission and that the cAMP/PKA pathway is associated with cognitive function. However, it is unclear whether they are responsible for the dual-task improving cognitive impairment in CCI. Bilateral common carotid artery occlusion (BCCAO) in SD rats was used to establish the CCI model. The effects of dual-task and single-task on cognitive function and the expressions of EphrinA3, EphA4, cAMP, and PKA in rats were detected by the novel object recognition (NOR) test, immunofluorescence staining, quantitative real-time polymerase chain reaction (qPCR), and Western blotting (WB), respectively. Overexpression or knockdown of EphrinA3 in astrocytes or rats were constructed by lentivirus infection to verify the effects of EphrinA3/EphA4 on the cAMP/PKA pathway. After dual-task intervention, the discrimination index of rats increased significantly compared with the rats in the CCI group. The expressions of EphrinA3 and EphA4 were decreased, while the expressions of cAMP and PKA were increased. Furthermore, knockdown of EphrinA3 alleviated the trend of CCI-induced cognitive decline in rats and OGD-stimulated cellular damage. It also increased cAMP/PKA expression in hippocampal neurons. Cognitive-exercise dual-task can significantly improve the cognitive impairment induced by CCI, and this effect may be better than that of the cognitive or exercise single-task intervention. The improvement may be related to the inhibition of EphrinA3/EphA4, followed by activation of the cAMP/PKA pathway.


High-frequency oscillatory ventilation, partial liquid ventilation, or conventional mechanical ventilation in newborn piglets with saline lavage-induced acute lung injury. A comparison of gas-exchange efficacy and lung histomorphology.
It has been reported that, in diseased lungs, either partial liquid ventilation (PLV) or high-frequency oscillatory ventilation (HFOV) can improve oxygenation better and with less lung injury than conventional mechanical ventilation (CMV). This study was intended as a preclinical comparison between the effects of HFOV, PLV and CMV on gas exchange, lung mechanics and histology. Fifteen anesthetized newborn piglets, with respiratory insufficiency due to repeated saline lung lavage, were allocated to either a PLV, HFOV or CMV (n = 5 each) strategy, and treated for 4 h. Within 30 min of commencing therapy, PLV, HFOV, and CMV improved arterial PO2 (Pa,O2), alveoloarterial oxygen gradient (P(A-a),O2), oxygenation index (OI), venous admixture (va), and arterial PCO2 (Pa,CO2). After 4 h, oxygenation parameters (Pa,O2, P(A-a),O2, OI and venous admixture) were significantly better in the HFOV group than in the PLV group; the CMV group showed a higher Pa,O2 and lower OI than the PLV group. Gas exchange at the end of the experiment was not different from baseline in the HFOV and CMV groups. Lung histology and morphometry were performed after perfusion-fixation at endotracheal deflation pressure corresponding to mean airway pressure at the end of the experiment. Lung injury score and mean linear intercept were not different between the three treatment groups. We conclude that in this model, gas exchange improved significantly in all three ventilation strategies. Indices of oxygenation improved less during PLV. The saline lavage-induced acute lung injury model used as in this study, is less stable than previously thought. The final lung injury is not influenced by the ventilation strategy. We speculate that the impaired gas exchange during PLV is an expression of diffusion limitation and ventilation-perfusion mismatch in a recovering lung.


[Emotional Support and Palliative Care for Distressed Patients Suffering from Pancreatic Cancer].
Pancreatic cancer is associated with a poor prognosis and high mortality. Thus, distress that includes depression and anxiety is a relatively common comorbidity for patients suffering from pancreatic cancer. However, these psychological symptoms are likely to be under-detected and undertreated. Regarding high levels of unmet needs of psychological support for patients with pancreatic cancer, early screening for distress and adequate interventions should be considered in palliative care settings. Suicide, a common but preventable cause of mortality for patients with pancreatic cancer, also deserves the further attention of care providers. Still, there have been limited studies that have documented psychological support for this population. Future research is needed to elucidate appropriate psychological care and models of services for patients suffering from pancreatic cancer.


Equine endotoxaemia--a state-of-the-art review of therapy.
The pathophysiology of endotoxaemia, a leading cause of death in the horse, is beginning to be understood in greater detail. Endotoxin may be absorbed into the systemic circulation in a number of different ways: most commonly the body's normal defense mechanisms are disrupted or bypassed, or the normal clearance mechanisms overwhelmed. Following this wide-spread effects are observed, although the most significant are seen in the cardiovascular system. Fever, arterial hypoxaemia and signs of abdominal pain are also common. With increased understanding of the disease new therapeutic agents have become available, however, while the newer agents offer some advantages it is important to recognise that supportive care is the mainstay of treatment for endotoxaemia. Supportive care consists of aggressive fluid therapy (crystalloid, colloid and hypertonic), the administration of non-steroidal antiinflammatory drugs and, where appropriate, antimicrobials. The principles of supportive care are discussed in detail. Other therapies such as hyperimmune plasma, polymyxin B, pentoxifylline, dimethyl sulfoxide and heparin are commonly used in the treatment of equine endotoxaemia and their use is reviewed here. Furthermore, newer agents such as anti-tumour necrosis factor antibodies, detergent, activated protein C and insulin, which have yet to gain widespread acceptance but may have an important role in the treatment of endotoxaemia in the future, are examined.


Synthetic anticancer vaccine candidates: rational design of antigenic peptide mimetics that activate tumor-specific T-cells.
A rational design approach was followed to develop peptidomimetic analogues of a cytotoxic T-cell epitope capable of stimulating T-cell responses as strong as or stronger (heteroclytic) than those of parental antigenic peptides. The work described herein focused on structural alterations of the central amino acids of the melanoma tumor-associated antigenic peptide Melan-A/MART-1(26-35) using nonpeptidic units. A screening was first realized in silico to select altered peptides potentially capable of fitting at the interface between the major histocompatibilty complex (MHC) class-I HLA-A2 molecule and T-cell receptors (TCRs). Two compounds appeared to be high-affinity ligands to the HLA-A2 molecule and stimulated several Melan-A/MART-1 specific T-cell clones. Most remarkably, one of them even managed to amplify the response of one clone. Together, these results indicate that central TCR-contact residues of antigenic peptides can be replaced by nonpeptidic motifs without loss of binding affinity to MHC class-I molecules and T-cell triggering capacity.


Variability of respiratory effort in relation to sleep stages in normal controls and upper airway resistance syndrome patients.
Investigation of the role of sleep states on the respiratory effort of controls and subjects with upper airway resistance syndrome (UARS) using nasal cannula/pressure transducer system and esophageal manometry. One night's monitoring of sleep and breathing, including the determination of peak end inspiratory esophageal pressure (respiratory effort) with esophageal manometry and flow limitation with nasal cannula. Analysis of the data, breath-by-breath, using visual inspection and a computerized program. Setting - a university sleep laboratory. Patients were nine men with UARS and nine control men matched for age, ethnicity, and body mass index. A modulation of respiratory effort by sleep state and stages is seen in all subjects, the lowest noted during REM sleep and the highest associated with Slow Wave Sleep. When total nocturnal breaths are investigated, a significant difference between peak end inspiratory esophageal pressure [(Pes)-considered as an index of respiratory effort] is noted between normal subjects and UARS. Two specific breathing patterns, seen primarily in UARS patients, are NREM sleep stage dependent. Crescendos (defined as more negative peak end inspiratory Pes with each successive abnormal breath) occur mostly during stages 1-2 NREM sleep, while segments consisting of regular and continuous, breath-after-breath, high respiratory efforts are associated with Slow Wave Sleep. Depending on sleep stage, visually scored arousal response displays differences in Pes negativity. The termination of the abnormal breathing pattern, always well defined with Pes, is not necessarily associated with a pattern of 'flow limitation' at the nasal cannula tracing, even when a visually scored EEG arousal is present. UARS patients have significantly more breaths, with more negative peak end inspiratory Pes, than do control subjects. The modulation of peak end inspiratory Pes (an index of respiratory effort) by sleep stage and state differs in UARS patients and control subjects. The nasal cannula/pressure transducer system may not detect all abnormal breathing pattern during sleep. As indicated by the visual sleep scoring, repetitive arousals may lead to more or less severe sleep fragmentation.


Anterior versus posterior treatment of stable thoracolumbar burst fractures without neurologic deficit: a prospective, randomized study.
A prospective randomized study was conducted to determine whether there exist any differences in radiographic, clinical, or functional outcomes when individuals with stable burst fractures of the thoracolumbar junction without neurologic deficit are treated with either a posterior fusion with instrumentation or anterior reconstruction, fusion, and instrumentation. There exists relatively little literature evaluating the outcomes of individuals treated with anterior surgery, and no prospective randomized studies exist comparing the two treatment approaches. From May 1995 to March 2001, a consecutive series of subjects with acute isolated burst fractures of the thoracolumbar junction (T10-L2) without neurologic deficit were randomized to receive either an anterior fusion with instrumentation or a posterior fusion with instrumentation. Radiographs including computed tomography (CT) were obtained. Radiographs were repeated at 2, 4, 6, 12, and 24 months. The CT scan was also repeated at 24 months. Hospital stay, cost, operating time, blood loss, complications, and patient-related functional outcomes were measured. Of 43 enrolled, 38 completed a minimum of 2-year follow-up (average: 43 months; range: 24-108 months). Eighteen received a posterior spine fusion and 20 an anterior approach. Hospital stay and operating time were similar. Blood loss was higher in the group treated anteriorly; however, the incidence of transfusion was the same. There were 17 "complications" including instrumentation removal for pain in 18 patients treated posteriorly, but only 3 minor complications in 3 patients treated anteriorly. Patient-related functional outcomes were similar for the two groups. Although patient outcomes are similar, anterior fusion and instrumentation for thoracolumbar burst fractures may present fewer complications or additional surgeries.


Long-term obturation quality using noninstrumentation technology.
The aim of the study was to evaluate and compare the sealing quality of hand- or vacuum-obturated root canals after hand instrumentation or noninstrumentation cleansing. A total of 60 single-rooted teeth were divided into six comparable groups. The root canals of three groups were instrumented with the balanced-force technique and obturated with gutta-percha condensation. The remaining teeth were cleansed and filled using noninstrumentation technology and the same sealers as with hand instrumentation (AH Plus, Apexit, Pulp canal sealer EWT). After aging the quality of coronal seal was assessed with a dye penetration method after perfusion with the dye under vacuum. The results of this study indicated superior sealing of the machine-filled roots (noninstrumentation technology), compared with laterally condensed conventionally filled root canals.


Intentions and willingness to engage in risky driving behaviour among high school adolescents: evaluating the bstreetsmart road safety programme.
To investigate the impact of a road safety programme on adolescents' willingness to engage in risky behaviour as probationary drivers, adjusted for covariates of interest. The bstreetsmart is a road safety programme delivered to around 25 000 adolescent students annually in New South Wales. Using a smartphone-based app, student and teacher participation incentives, students were surveyed before and after programme attendance. Mixed-methods linear regression analysed pre/post-modified Behaviour of Young Novice Driver (BYNDS_M) scores. 2360 and 1260 students completed pre-event and post-event surveys, respectively. Post-event BYNDS_M scores were around three points lower than pre-event scores (-2.99, 95% CI -3.418 to -2.466), indicating reduced intention to engage in risky driving behaviours. Covariates associated with higher stated intentions of risky driving were exposure to risky driving as a passenger (1.21, 95% CI 0.622 to 2.011) and identifying as non-binary gender (2.48, 95% CI 1.879 to 4.085), adjusting for other predictors. Trauma-informed, reality-based injury prevention programmes can be effective in changing short-term stated intentions to engage in risky driving, among a pre-independent driving student population. The adolescent novice driver age group is historically challenging to engage, and injury prevention action must be multipronged to address the many factors influencing their behaviour.


Inhibition of protein synthesis and secretion by volatile anesthetics in guinea pig liver slices.
The decrease in protein synthesis and secretion caused by volatile anesthetics was investigated using Hartley male guinea pig liver slices. Precision-cut liver slices (250-300 mM thick) were incubated in sealed roller vials (3 slices/vial) containing Krebs-Hensleit buffer at 37 degrees C under 95% O2 atmosphere. Volatile anesthetics were injected through a teflon septa cap on a filter paper wick and vaporized to produce constant concentration in the medium. A concentration (1-2.1 mM) and time related (0-24) decrease in protein synthesis (3H-leucine incorporation) and secretion by halothane and d-halothane was observed. d-Halothane was less inhibiting than halothane. Inhibition was not on the uptake of the 3H-leucine but with its incorporation in the nascent peptide. The effects of enflurane (2.2 mM), isoflurane (2.2 mM), and sevoflurane (1.3 mM) on protein synthesis and secretion were also studied. The rank order of decrease in protein synthesis caused by the volatile anesthetics studied was halothane greater than isoflurane greater than enflurane greater than sevofluane greater than d-halothane. Enflurane, isoflurane, and sevoflurane increased the protein secretion while halothane and d-halothane caused a pronounced decrease. Alterations in protein synthesis and secretion appears to be an early and sensitive indicator of cytotoxin injury.


[Osteo-gingivoplasty in the combined treatment of periodontitis and in the prevention of odontogenic maxillary sinusitis at a polyclinic].
The authors suggest a method for surgical treatment of periodontitis using allogenic demineralized bone tissue of adults and fetuses. This method was effectively used at dentistry clinics of the Samara Province starting from 1984. A total of 177 patients with generalized and local periodontitis of medium and grave severity aged 19 to 55 were operated on. The process stabilized, the teeth were fortified. The method is effective not only therapy of periodontitis, but for prevention of its complications as well, of odontogenic maxillary sinusitis among other conditions.


Clinical phenotypes associated with the complement factor H Y402H variant in age-related macular degeneration.
To determine whether the complement factor H (CFH) Y402H variant is associated with specific age-related macular degeneration (AMD) clinical phenotypes. Retrospective, case-control study. One hundred and eighty-eight white subjects with AMD and 189 control subjects were genotyped for the T-to-C polymorphism in exon 9 of the CFH gene by restriction-fragment length analysis and deoxyribonucleic acid (DNA) sequencing using genomic DNA from mouthwash samples. AMD phenotypes were characterized by clinical examination, fundus photography, and fluorescein angiography. Heterozygosity for the at-risk genotype (TC) increased the likelihood for AMD 2.1-fold (95% confidence interval [CI], 1.3 to 3.3), whereas homozygosity for the genotype (CC) increased the likelihood for AMD 6.5-fold (95% CI, 3.4 to 12.5) in our population. The C allele was associated significantly with predominantly classic choroidal neovascularization (odds ratio [OR], 2.01; 95% CI, 1.34 to 3.30). Neovascular lesion size was similar among the three genotypes (P = .67). The Y402H CFH variant carried a significantly increased risk for developing AMD in our population. Genotype and phenotype correlations regarding choroidal neovascular lesion type were observed.


Household availability of ultra-processed foods and obesity in nineteen European countries.
To assess household availability of NOVA food groups in nineteen European countries and to analyse the association between availability of ultra-processed foods and prevalence of obesity. Ecological, cross-sectional study. Europe. Estimates of ultra-processed foods calculated from national household budget surveys conducted between 1991 and 2008. Estimates of obesity prevalence obtained from national surveys undertaken near the budget survey time. Across the nineteen countries, median average household availability amounted to 33·9 % of total purchased dietary energy for unprocessed or minimally processed foods, 20·3 % for processed culinary ingredients, 19·6 % for processed foods and 26·4 % for ultra-processed foods. The average household availability of ultra-processed foods ranged from 10·2 % in Portugal and 13·4 % in Italy to 46·2 % in Germany and 50·4 % in the UK. A significant positive association was found between national household availability of ultra-processed foods and national prevalence of obesity among adults. After adjustment for national income, prevalence of physical inactivity, prevalence of smoking, measured or self-reported prevalence of obesity, and time lag between estimates on household food availability and obesity, each percentage point increase in the household availability of ultra-processed foods resulted in an increase of 0·25 percentage points in obesity prevalence. The study contributes to a growing literature showing that the consumption of ultra-processed foods is associated with an increased risk of diet-related non-communicable diseases. Its findings reinforce the need for public policies and actions that promote consumption of unprocessed or minimally processed foods and make ultra-processed foods less available and affordable.


Evolving concepts in the treatment of traumatic aortic injury. A review article.
Traumatic aortic injury (TAI) has long been considered a surgical emergency, despite the high mortality and morbidity rates in traumatized patients submitted to open surgery. Initial medical management until stabilization of associated traumatic lesions has long been a matter of debate because of the inherent risk of rupture in some of these cases. Endovascular techniques in the management of polytraumatized patients provides an additional low-invasive treatment option. Because of its lower invasiveness, without thoracotomy or the use of heparin, endovascular repair can be performed in acute patients, without the risk of destabilizing pulmonary, head or abdominal traumatic lesions. Following the publication of early small series and case reports, endovascular repair has become a widely accepted method for treating both acute and chronic traumatic lesions. Our series comprised 51 TAI patients submitted to endovascular aneurysm repair from July 1997 to December 2006, of which 24 had chronic post-traumatic aneurysms and 27 were treated in the acute or subacute phase after the traumatic event. No mortality occurred; aneurysm sealing was consistently good. Major complications included a cerebellar stroke in 1 patient due to occlusion of the left subclavian artery. No failure of aortic procedure, mortality or complications were observed during the follow-up period. Should long-term follow-up in larger series show substantial durability of the graft material, endovascular treatment will become the management of choice for TAIs.


Hand contamination with human rhinovirus in Bangladesh.
As one step in developing a measure of hand contamination with respiratory viruses, this study assessed if human rhinovirus (HRV) was detectable on hands in a low income non-temperate community where respiratory disease is a leading cause of child death. Research assistants observed residents in a low income community in Dhaka, Bangladesh. When they observed a resident sneeze or pick their nose, they collected a hand rinse and anterior nare sample from the resident. Samples were first tested for HRV RNA by real-time RT-PCR (rRT-PCR). A subset of rRT-PCR positive samples were cultured into MRC-5 and HeLa Ohio cells. Among 177 hand samples tested for HRV by real-time RT-PCR, 52 (29%) were positive. Among 15 RT-PCR positive hand samples that were cultured, two grew HRV. HRV was detected in each of the sampling months (January, February, June, July, November, and December). This study demonstrates in the natural setting that, at least after sneezing or nasal cleaning, hands were contaminated commonly with potentially infectious HRV. Future research could explore if HRV RNA is present consistently and is associated sufficiently with the incidence of respiratory illness in communities that it may provide a proxy measure of respiratory viral hand contamination.


[Repeated anti-reflux operations].
The authors had under observation 73 patients who underwent various antireflux operations with poor results, 68 of them were subjected to repeated interventions, fundoplication in most cases. The causes of failure of primary and repeated antireflux operations are analysed, the indications for and the techniques of reconstructive interventions are discussed. It is emphasized that patients with hiatal hernia and reflux esophagitis must be concentrated in specialized medical institutions.


Deploying green hydrogen to decarbonize China's coal chemical sector.
China's coal chemical sector uses coal as both a fuel and feedstock and its increasing greenhouse gas (GHG) emissions are hard to abate by electrification alone. Here we explore the GHG mitigation potential and costs for onsite deployment of green H2 and O2 in China's coal chemical sector, using a life-cycle assessment and techno-economic analyses. We estimate that China's coal chemical production resulted in GHG emissions of 1.1 gigaton CO2 equivalent (GtCO2eq) in 2020, equal to 9% of national emissions. We project GHG emissions from China's coal chemical production in 2030 to be 1.3 GtCO2eq, ~50% of which can be reduced by using solar or wind power-based electrolytic H2 and O2 to replace coal-based H2 and air separation-based O2 at a cost of 10 or 153 Chinese Yuan (CNY)/tCO2eq, respectively. We suggest that provincial regions determine whether to use solar or wind power for water electrolysis based on lowest cost options, which collectively reduce 53% of the 2030 baseline GHG emissions at a cost of 9 CNY/tCO2eq. Inner Mongolia, Shaanxi, Ningxia, and Xinjiang collectively account for 52% of total GHG mitigation with net cost reductions. These regions are well suited for pilot policies to advance demonstration projects.


Associations of Behavioral Disorders with Asthma in Iranian Children.
Asthma is a common respiratory disease with huge economic burden leading to activity limitations, morbidity, and mortality. In this study, we aim to investigate the prevalence of Oppositional Defiant Disorder (ODD), Attention Deficit Hyperactivity Disorder (ADHD) and Conduct Disorder (CD) among children with asthma. This case-control study was performed in a pediatric referral health care center(Children's Medical CenterinTehran University of Medical Sciences) in 2017.With random selection, the 80 children with asthma and 92 controls with age range of 5 to 11 years were enrolled in this study. In addition to the demographic information and family history of allergy, asthma symptoms, and control quality evaluated with a validated Childhood Asthma Control Test (C-ACT). The mode of measurement for ADHD, ODD and CD was based on Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) psychiatric scales from clinical interviews conducted by child psychiatrists. Totally, 42.5% and 25% in the case and control groups had ADHD respectively withsignificant difference (p=0.01). Also, 25% and 5.4% in thecase and control groups had ODD respectively with significant difference (p=0.001). But conduct disorder was 10% and 10.9% in case and control groups respectively without significant difference (p=0.8). Children with asthma were associated with exhibiting ADHD and ODD but not CD. Therefore, appropriate evaluation and treatment are needed for asthmatic children with attention-deficit and ODD symptoms. Besides, further research is needed to determine the etiological approach towards ADHD, ODD and asthma.


Chemosensitivity testing of oral cancer cells treated with a p185neu-specific agent.
The amplification and overexpression of the erbB-2 oncogene and its involvement in tumorigenesis makes this receptor an appropriate target for specific agents directed towards tumor cells. The purpose of this study was to evaluate the in vitro effect of the bacterially produced recombinant immunotoxin scFv(FRP5)-ETA on the protein synthesis and adenosine triphosphate (ATP) reduction in oral squamous cell carcinoma (OSCC) cells. This agent recognizes the erbB-2 receptor and inhibits protein synthesis in receptor-overexpressing cells. OSCC cells were selected for this study, and amplification and expression levels of the erbB-2 receptor were determined. Cell suspensions were cultured for 6 d with various concentrations of scFv(FRP5)-ETA (1-1000 ng/ml). A431 and MDA-MB468 cell lines were used as controls. Chemosensibility of tumor cells was measured by [3H]leucine incorporation assay and by an ATP luminescence assay. In OSCC cells with amplification and overexpression of erbB-2 inhibition, up to 92% of protein synthesis and 90% of ATP reduction was observed when cells were exposed to 1,000 ng/ml immunotoxin. In OSCC cells showing a deletion of erbB-2 and in erbB-2-negative MDA-MB468 cells, protein synthesis was inhibited by 22% and 8%, respectively. These results indicate that the effectiveness of a recombinant immunotoxin targeting erbB-2 receptors in OSCC cells depends on the level of erbB-2 amplification and expression, that it is highly specific for tumor cells expressing these receptors, and that a dose-dependency can be observed.


Primary hormonal treatment in localized and locally advanced prostate cancer: effectiveness and survival predictive factors.
to evaluate the effectiveness of primary hormonal treatment on localized and locally advanced prostate cancer, including the analysis on the survival predictive factors. patients with localized (T1,T2N0M0) and locally advanced (T3, T4N0M0) prostate cancer who had received primary hormonal treatment between January 1995 and December 2009 were evaluated retrospectively based on their specific medical records at Department of Urology in Cipto Mangunkusumo Hospital (RSCM) and Dharmais Cancer Hospital (RSKD). about 79 (29.9%) of 264 patients with localized and advanced local prostate cancer received primary hormonal treatment. In the localized prostate cancer group, mean survival was 58.3 months (range: 1.87-170.78) and 5-year survival was 77.3%; while in locally advanced prostate cancer patients, mean survival was 40.87 months (range 7.29-115.29) and 5-year survival was only 22.7%. Hemoglobin level was a significant clinical parameter of survival predictive factors for both localized and locally advanced prostate cancer groups. The lower the hemoglobin level, the survival will be shorter. there were no significant differences between mean survival and 5-year survival rate, between localized and locally advanced prostate cancer patients who had received primary hormonal treatment. Hemoglobin level is survival predictive factors for localized and locally advanced prostate cancer patients.


Effect of dietary fats and proteins on drug metabolism.
Rats were given diets ad libitum which varied in the amount (5 or 15%) and kind of fat [coconut oil (CNO) vs corn oil (CO)]. Animals were injected either with hexobarbital or pentobarbital and sleeping time was recorded. With animals eating a low fat diet, there were slight differences between the CNO vs CO groups. At the higher fat level, animals receiving the polyunsaturated diet slept more than twice as long as compared to animals eating a diet with saturated oil. Simultaneous injection with carbon tetrachloride significantly increased the sleeping time between the two dietary fat groups. Also, the kind of protein and level of fat in the diet had an influence on sleeping times. It was concluded that both the quality and quantity of fat as well as the quality of the protein can influence drug metabolism.


Bowl is required downstream of Notch for elaboration of distal limb patterning.
In the Drosophila leg, activation of Notch leads to the establishment of the joints that subdivide the appendage into segments. We find that mutations in bowl result in similar phenotypes to Notch, causing fusion and truncations of tarsal segments (tarsomeres) and, like its close relative Odd-skipped, Bowl is produced in response to Notch signalling at a subset of segment boundaries. However, despite the fact that bowl mutant clones result in fusion of tarsomeres, Bowl protein is only found at the t1/tibial and t5/pretarsal boundaries, not at tarsomere joints. One hypothesis to reconcile these data is that bowl has a role at an earlier stage in tarsal development. We therefore investigated the effects of bowl mutations on the expression of leg 'gap' genes that confer regional identity on the developing leg. Several of these genes have altered expression in bowl mutant cells. For example, bric-a-brac2 is normally expressed in the central part of the tarsus domain but expands into distal and proximal regions in bowl clones. Conversely, ectopic bowl leads to a reduction in bric-a-brac2, with a concomitant expansion of proximal (t1) and distal (t5) tarsomere fates. The bowl gene is therefore required for the elaboration of pattern in the tarsus and its effects suggest a progressive model for the determination of P/D identities. This mechanism might be important in the diversification of arthropod limbs, because it explains how segmented tarsomeres could have arisen from an ancestral limb with an unsegmented tarsus.


Demographic Differences in Life Dissatisfaction Among Adults: United States, 2021.
Objective-Previous work has established life satisfaction as an important indicator of overall health and well-being. This report describes differences in life dissatisfaction by selected characteristics, grouped by family income. Methods-Data from the 2021 National Health Interview Survey were used to examine the percentage of adults that were dissatisfied with life by selected demographic characteristics (age, sex, race and Hispanic origin, and nativity status [born in the United States or U.S. territory]), grouped by family income. Results-In 2021, 4.8% of adults were dissatisfied with life. In general, analyses showed significant differences by all selected demographic characteristics among adults with incomes of less than 200% of the federal poverty level. Among this group, men, adults ages 45-64, White non-Hispanic adults, Black non-Hispanic adults, and adults born in the United States were more likely to be dissatisfied with life compared with their counterparts. No significant differences in life dissatisfaction by selected demographic characteristics among adults with incomes greater than 200% of the federal poverty level were observed. Conclusion-This report presents estimates of life dissatisfaction among adults by demographic subgroups and family income. These results highlight the importance of monitoring life dissatisfaction among detailed subgroups grouped by income, in addition to the overall national estimate.


Drugs don't work in patients who don't take them: Dr. Drin, the new ICT paradigm for chronic therapies.
Poor adherence to drug therapies still represents an unsolved problem. In order to provide a useful solution to chronic patients of all ages--with particular attention to the elderly--who are subjected to complex therapeutic regimen, an innovative ICT solution, called Dr.Drin, has been designed and tested. The aim of the developed framework is to assist the patient during the therapy and to enable and support a bidirectional communication between all healthcare stakeholders (doctors, caregivers and family members) and the patient. During the screening phase, patients were interviewed to understand what are the common practices they usually adopt to remember when and how to take a drug. The solutions which they rely the most on are the list of drugs, writing on the packaging, and setting up alarms. Patients who complained about difficulties of adherence and who had a smartphone were subsequently recruited to test Dr.Drin over a three-months period. In the following, preliminary results from the first twelve patients are presented and analyzed to prove the effectiveness of Dr.Drin in supporting patients adherence to therapies.


Efficacy and safety of intranasal esketamine for the treatment of major depressive disorder.
Introduction: In March 2019, intranasal esketamine was approved by the Food and Drug Administration (FDA) for the treatment of treatment-resistant depression (TRD) in adults. This review presents the results of clinical trials underlying the FDA approval of intranasal esketamine.Areas covered: Esketamine's efficacy and safety in TRD were assessed in 5 phase III studies: three 4-week, placebo-controlled studies, and two long-term trials. One short-term trial showed statistically significant antidepressant effects of esketamine vs placebo, while a long-term withdrawal study showed that esketamine is significantly beneficial in terms of extending time to relapse, compared to placebo. Two other short-term trials did not meet the prespecified statistical tests for showing efficacy, although improvement in depressive symptoms from baseline to the end of week 4 favors esketamine over placebo.Expert opinion: Intranasal esketamine is a new treatment option for people with TRD. The main benefit of esketamine is rapid onset of antidepressant activity, but the effects of prolonged treatment are still preliminary. The main concerns relate to the safety aspects of prolonged esketamine therapy, when considering its abuse potential. While data for esketamine use over a long period of time is lacking, its use should be carefully monitored.


Pregnancy and COVID-19: prevention, vaccination, therapy, and beyond
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has alarmed the world since its first emergence. As pregnancy is characterized by significant changes in cardiovascular, respiratory, endocrine, and immunological systems, there are concerns on issues like the course of disease in pregnant women, safety of medications, route of delivery and risk of obstetric complications. The aim of this review is to summarize the current literature in the management of pregnant women during the COVID-19 pandemic. Although more than 90% of pregnant women with COVID-19 recover without serious morbidity, rapid deterioration of disease and higher rates of obstetric complications may be observed. The risk of vertical transmission has not been clearly revealed yet. Decreasing the number of prenatal visits, shortening the time allocated for the examinations, active use of telemedicine services, limiting the number of persons in healthcare settings, combining prenatal tests in the same visit, restricting visitors during the visits, providing a safe environment in healthcare facilities, strict hygiene control, and providing personal protective equipment during the visits are the main strategies to control the spread of disease according to current guidelines. Although new medication alternatives are being proposed every day for the treatment of COVID-19, our knowledge about the use of most of these drugs in pregnancy is limited. Preliminary results are promising for the administration of SARS-CoV-2 vaccines in the pregnant population. Timing of delivery should be decided based on maternal health condition, accompanying obstetric complications and gestational age. Cesarean delivery should be performed for obstetric indications. Breast feeding should be encouraged as long as necessary precautions for viral transmission are taken. In conclusion, an individualized approach should be provided by a multidisciplinary team for the management of pregnant women with COVID-19 to achieve favorable outcomes.


Using economic information in a quality improvement collaborative.
This article provides an overview of neonatal intensive care unit treatment costs for hospitals that participated in the Neonatal Intensive Care Quality Improvement Collaborative Year 2000 (NIC/Q 2000) quality improvement collaborative and discusses how economic information can be used in quality improvement efforts. Detailed information on neonatal intensive care unit treatment costs is presented for 29 hospitals that participated in the NIC/Q 2000 collaborative. The sample consists of 6797 very low birth weight infants (1500 g or less at birth) with admission dates between January 1, 1997, and December 31, 1998. Information on median treatment cost per infant, ancillary costs, accommodation costs, length of stay, and cost per day is presented. In addition, ancillary costs are further disaggregated into those for respiratory therapy, laboratory, radiology, pharmacy, and all other ancillary services. The role of level of care and other factors that influence treatment costs are then explored.


Molecular insight into the electrostatic membrane surface potential by 14n/31p MAS NMR spectroscopy: nociceptin-lipid association.
Exploiting naturally abundant (14)N and (31)P nuclei by high-resolution MAS NMR (magic angle spinning nuclear magnetic resonance) provides a molecular view of the electrostatic potential present at the surface of biological model membranes, the electrostatic charge distribution across the membrane interface, and changes that occur upon peptide association. The spectral resolution in (31)P and (14)N MAS NMR spectra is sufficient to probe directly the negatively charged phosphate and positively charged choline segment of the electrostatic P(-)-O-CH(2)-CH(2)-N(+)(CH(3))(3) headgroup dipole of zwitterionic DMPC (dimyristoylphosphatidylcholine) in mixed-lipid systems. The isotropic shifts report on the size of the potential existing at the phosphate and ammonium group within the lipid headgroup while the chemical shielding anisotropy ((31)P) and anisotropic quadrupolar interaction ((14)N) characterize changes in headgroup orientation in response to surface potential. The (31)P/(14)N isotropic chemical shifts for DMPC show opposing systematic changes in response to changing membrane potential, reflecting the size of the electrostatic potential at opposing ends of the P(-)-N(+) dipole. The orientational response of the DMPC lipid headgroup to electrostatic surface variations is visible in the anisotropic features of (14)N and (31)P NMR spectra. These features are analyzed in terms of a modified "molecular voltmeter" model, with changes in dynamic averaging reflecting the tilt of the C(beta)-N(+)(CH)(3) choline and PO(4)(-) segment. These properties have been exploited to characterize the changes in surface potential upon the binding of nociceptin to negatively charged membranes, a process assumed to proceed its agonistic binding to its opoid G-protein coupled receptor.


[Production of transgenic sugarbeet (Beta vulgaris L.) plants of O-type using Agrobacterium tumefaciens].
A method of Agrobacterium-mediated genetic transformation of sugarbeet (Beta vulgaris L.) by vacuum infiltration has been developed. Transgenic sugarbeet plants of Ukraine breeding were selected for their resistance either to the antibiotic kanamycin or to the herbicide glufosinate ammonium. Integration of transgenes was confirmed by PCR and GUS-assay.


Is liver biopsy necessary in the management of alcoholic hepatitis?
Acute alcoholic hepatitis (AAH) is characterised by deep jaundice in patients with a history of heavy alcohol use, which can progress to liver failure. A clinical diagnosis of AAH can be challenging to make in patients without a clear alcohol history or in the presence of risk factors for other causes of acute liver failure. Other causes of acute on chronic liver failure such as sepsis or variceal haemorrhage should be considered. Liver biopsy remains the only reliable method to make an accurate diagnosis. However, there is controversy surrounding the use of liver biopsy in patients with AAH because of the risks of performing a percutaneous biopsy and limitations in access to transjugular biopsy. We review the existing literature and find there are few studies directly comparing clinical and histological diagnosis of AAH. In the small number of studies that have been conducted the correlation between a clinical and histological diagnosis of AAH is poor. Due to this lack of agreement together with difficulties in accessing transjugular liver biopsy outside tertiary referral centres and research institutions, we cannot advocate universal biopsy for AAH but there remains a definite role for liver biopsy where there is clinical diagnostic doubt or dual pathology. It also adds value in a clinical trial context to ensure a homogeneous trial population and to further our understanding of the disease pathology. Further prospective studies are required to determine whether non-invasive markers can be used to accurately diagnose AAH.


PLK1 promotes the mitotic surveillance pathway by controlling cytosolic 53BP1 availability.
53BP1 acts at the crossroads between DNA repair and p53-mediated stress response. With its interactors p53 and USP28, it is part of the mitotic surveillance (or mitotic stopwatch) pathway (MSP), a sensor that monitors the duration of cell division, promoting p53-dependent cell cycle arrest when a critical time threshold is surpassed. Here, we show that Polo-like kinase 1 (PLK1) activity is essential for the time-dependent release of 53BP1 from kinetochores. PLK1 inhibition, which leads to 53BP1 persistence at kinetochores, prevents cytosolic 53BP1 association with p53 and results in a blunted MSP. Strikingly, the identification of CENP-F as the kinetochore docking partner of 53BP1 enabled us to show that measurement of mitotic timing by the MSP does not take place at kinetochores, as perturbing CENP-F-53BP1 binding had no measurable impact on the MSP. Taken together, we propose that PLK1 supports the MSP by generating a cytosolic pool of 53BP1 and that an unknown cytosolic mechanism enables the measurement of mitotic duration.


[Household water reservoirs and control of Aedes aegypti].
Water reservoirs for domestic use are important sites for the development of Aedes aegypti. In poor areas, these reservoirs are often located outdoors upon flat rooftops. In modern architecture buildings, however, the same is seen even in high-class condominiums. Special attention should be given to these modern architectural constructions during entomological surveillance.


Administration of ginger and/or thyme has ameliorative effects on liver and kidney functions of V-line rabbits: Histological and biochemical studies.
This study was conducted to evaluate the effect of Zingiber officinale and Thymus vulgaris aqueous extracts as a natural antioxidant on liver and kidney functions and antioxidant status of growing rabbits. A total of 24 V-line male rabbits, 3 months old, 1.465 ± 0.12 kg average body weight (BW) were used in a complete randomized design. The rabbits were weighed individually and assigned randomly to four groups (6 animals/each). The first group (G1) was taken fresh water and served as control, rabbits of the second group (G2) were taken 100 mg/kg BW in drinking water of the Z. officinale aqueous extract daily. The third group (G3) was taken 50 mg/kg BW in drinking water of the T. vulgaris aqueous extract daily and the fourth group (G4) was taken 100 mg/kg BW of the Z. officinale aqueous extract plus 50 mg/kg BW of the T. vulgaris aqueous extract in drinking water daily. The oral administration of ginger and/or thyme aqueous extracts increased (p < .001) serum protein profile compared with control group. Moreover, results of group 2 showed significant (p < .001) decrease in cholesterol, triglyceride and very low-density lipoprotein cholesterol compared with group 3 and 4. Serum urea, uric acid and creatinine levels were significantly (p < .001) decreased in treated groups compared with control group. Oral administration of ginger and/or thyme aqueous extracts to growing rabbits increased (p < .001) total antioxidant capacity and glutathione content and the activity of superoxide dismutase, catalase and glutathione-S-transferase compared with the control group. In conclusion, the current study showed that oral administration of ginger and thyme aqueous extracts to growing rabbits showed no adverse effects on liver and kidney function parameters, histological structures and improved antioxidant status.


Management of war-related vascular injuries: experience from the second gulf war.
To study the biomechanism, pattern of injury, management, and outcome of major vascular injuries treated at Mubarak Al-Kabeer Teaching Hospital, Kuwait during the Second Gulf War. This is a descriptive retrospective study. War-related injured patients who had major vascular injuries and were treated at Mubarak Al-Kabeer Teaching Hospital from August 1990 to September 1991 were studied. Studied variables included age, gender, anatomical site of vascular injury, mechanism of injury, associated injuries, type of vascular repair, and clinical outcome. 36 patients having a mean (SD) age of 29.8 (10.2) years were studied. 32 (89%) were males and 21 (58%) were civilians. Majority of injuries were caused by bullets (47.2%) and blast injuries (47.2%). Eight patients (22%) presented with shock.There were 31 arterial injuries, common and superficial femoral artery injuries were most common (10/31). Arterial repair included interposition saphenous vein graft in seven patients, thrombectomy with end-to-end / lateral repair in twelve patients, vein patch in two patients, and arterial ligation in four patients. Six patients had arterial ligation as part of primary amputation. 3/21 (14.3%) patients had secondary amputation after attempted arterial vascular repair of an extremity. There were a total of 17 venous injuries, 13 managed by lateral suture repair and 4 by ligation. The median (range) hospital stay was 8 (1-76) days. 5 patients died (14%). Major vascular injuries occurred in 10% of hospitalized war-related injured patients. Our secondary amputation rate of extremities was 14%. The presence of a vascular surgeon within a military surgical team is highly recommended. Basic principles and techniques of vascular repair remain an essential part of training general surgeons because it may be needed in unexpected wars.


A data-driven, high-throughput methodology to determine tissue-specific differentially methylated regions able to discriminate body fluids.
Tissue-specific differentially methylated regions (tDMRs) are regions of the genome with methylation patterns that modulate gene expression in those tissue types. The detection of tDMRs in forensic evidence can permit the identification of body fluids at trace levels. In this report, we have performed a bioinformatic analysis of an existing array dataset to determine if new tDMRs could be identified for use in body fluid identification from forensic evidence. Once these sites were identified, primers were designed and bisulfite modification was performed. The relative methylation level for each body fluid at a given locus was then determined using qPCR with high-resolution melt analysis (HRM). After screening 127 tDMR's in multiple body fluids, we were able to identify four new markers able to discriminate blood (2 markers), vaginal epithelia (1 marker) and buccal cells (1 marker). One marker for each target body fluid was also tested with pyrosequencing showing results consistent with those obtained by HRM. This work successfully demonstrates the ability of in silico analysis to develop a novel set of tDMRs capable of being differentiated by real time PCR/HRM. The method can rapidly determine the body fluids left at crime scenes, assisting the triers of fact in forensic casework.


Efficient transcription of a Caenorhabditis elegans heat shock gene pair in mouse fibroblasts is dependent on multiple promoter elements which can function bidirectionally.
A divergently transcribed pair of Caenorhabditis elegans hsp16 genes was introduced into mouse fibroblasts by stable transfection with vectors containing bovine papillomavirus plasmid maintenance sequences and a selectable gene. The hsp16 genes were transcriptionally inactive in the mouse cells under normal growth conditions and were strongly induced by heat shock or arsenite. In a cell line with 12 copies of the gene pair, there were estimated to be more than 10,000 hsp16 transcripts in each cell after 2 h of heat shock treatment. The hsp16 transcript levels were more than 100 times higher than those of a gene with a herpes simplex virus thymidine kinase gene promoter carried on the same vector. A single heat shock promoter element (HSE) could activate bidirectional transcription of the two hsp16 genes when placed between the two TATA elements, but the transcriptional efficiency was reduced 10-fold relative to that of the wild-type gene pair. Four overlapping HSEs positioned between the two TATA elements resulted in inducible bidirectional transcription at greater than wild-type levels. The number of HSEs can therefore be a major determinant of the promoter strength of heat-inducible genes in mammalian cells. Partial disruption of an alternating purine-pyrimidine sequence between the two hsp16 genes had no significant effect on their transcriptional activity.


[Factorial validation of the French scale for perceived stress in the workplace].
This article aims to validate the factorial structure of the perceived stress scale (PSS10) within the French working population. The analyses conducted confirmed the presence of two distinct factors, interpreted in terms of perceived work overload and perceived personal efficacy. Both factors presented good internal consistency and adequate validity of construct. The authors show and illustrate the predicted link between the two factors and the levels of anxiety and depression. Thus, the PSS 10 is a bi-dimensional scale with satisfactory psychometric proprieties. The results are discussed in the light of their theoretical and practical implications.


Automatic measurement and visualization of focal femoral cartilage thickness in stress-based regions of interest using three-dimensional knee models.
Thinning of cartilage is a common manifestation of osteoarthritis. This study addresses the need of measuring the focal femoral cartilage thickness at the weight- bearing regions of the knee by developing a reproducible and automatic method from MR images. 3D models derived from semiautomatic MR image segmentations were used in this study. Two different methods were examined for identifying the mechanical loading of the knee articulation. The first was based on a generic weight-bearing regions definition, derived from gait characteristics and cadaver studies. The second used a physically based simulation to identify the patient-specific stress distribution of the femoral cartilage, taking into account the forces and movements of the knee. For this purpose, four different scenarios were defined in our 3D finite element (FE) simulations. The radial method was used to calculate the cartilage thickness in stress-based regions of interest, and a study was performed to validate the accuracy and suitability of the radial thickness measurements. Detailed focal maps using our simulation data and regional measurements of cartilage thickness are given. We present the outcome of the different simulation scenarios and discuss how the internal/external rotations of the knee alter the overall stress distribution and affect the shape and size of the calculated weight-bearing areas. The use of FE simulations allows for a patient-specific calculation of the focal cartilage thickness. It is important to assess the quantification of focal knee cartilage morphology to monitor the progression of joint diseases or related treatments. When this assessment is based on MR images, accurate and robust tools are required. In this paper, we presented a set of techniques and methodologies in order to accomplish this goal and move toward personalized medicine.


Use of a central laboratory for analysis of bronchoalveolar lavage fluid.
The logistics and related costs were assessed for providing analysis of bronchoalveolar lavage (BAL) fluid in a central laboratory for practicing pulmonologists in the area around New Haven, Connecticut. During a 4-yr period (1981-1985) we arranged for a courier service to transport 175 BAL specimens, obtained by 22 participating physicians at the time of fiberoptic bronchoscopy, directly to our laboratory. A large battery of information was generated on each specimen, and the data were returned to the responsible physician within 24 h. Any remaining cells and the cell-free supernatants were used for additional research purposes. The primary benefits of this program included: rapid and standardized analysis of lavage fluid cell counts for the clinician to use along with historical and other more routine laboratory tests in guiding patient diagnosis and an augmented number of lavage specimens available to the academician for research purposes. The costs were judged to be reasonable but need to be factored into the overall costs of patient diagnostic evaluations.


Masticatory function in subacute TMD patients before and after treatment.
Masticatory function can be impaired in temporomandibular disorders (TMDs) patients. We investigated whether treatment of subacute non-specific TMD patients may influence oral function and clinical outcome measures. Fifteen patients with subacute TMD participated in the study. We quantified masticatory performance, maximum voluntary bite force, muscle activity and chewing cycle duration before and after treatment. Masticatory performance and bite force of patients were compared with the results obtained for an age- and gender-matched group of subjects without TMD complaints. Furthermore, we determined possible changes in anamnestic and clinical scores from questionnaires (mandibular function impairment questionnaire; MFIQ), pain scores and clinical outcome measures. Maximum bite force significantly increased, although the values after treatment were still significantly lower than those of the subjects without TMD complaints. The corresponding electromyography values did not show significant change after treatment. The masticatory performance of the patients remained unaltered; patients chewed significantly less efficient than controls. The average duration of chewing cycles significantly decreased after treatment. We observed a significant improvement in MFIQ scores. During the clenching and chewing tasks, the visual analogue scale scores were significantly higher than before these tasks. We may conclude that subacute temporomandibular joint disorders negatively influence chewing behaviour. Bite force, chewing cycle duration and also perceived mandibular function significantly improved after treatment, although the masticatory performance remained unaltered.


Stabilization of DNA liquid crystals on doping with gold nanorods.
We report on the impact of doping with gold nanorods (NRs) on the formation and stability of DNA liquid crystals (LCs). Cetyl trimethylammonium (CTAB)-stabilized gold NRs were synthesized using the wet chemistry method. Different textures of cholesteric and columnar mesophases, as well as phase transitions, were observed using a polarized light microscope. It was found that liquid crystalline phases formed in the samples were qualitatively the same and the phase appearance sequence was preserved in the samples regardless of the doping. We show that depending on the concentration of gold NRs present in the phase, nanoparticle-doped cholesteric and columnar hexagonal phases existed in wider temperature ranges compared to pure DNA LCs. The potential applications of these liquid crystal-nanoparticle hybrid systems may include the fabrication of new optoelectronic devices and sensors.


[EFFECTS OF URSODEOXYCHOLIC ACID IN STANDART INTERFERONTHERAPY OF PATIENTS WITH CHRONIC HEPATITIS C AND B].
With the purpose to estimate the efficiency of ursodeoxycholic acid (UDCA) in standard antiviral therapy (SAT) of chronic hepatitis C or/and B 580 patients with the chronic virus hepatitis enrolled in this study. During 48 weeks patients with hepatitis B and B+D received peg-interferon, and patients with C and B+C hepatitis received combined peg-interferon and ribavirin. 1st group of 300 patients (B--130, C--96, B+C--73, B+D--10; 190 men, 110 women, middle age of 32.9 ± 10.1 years) additionally took UDCA not less than 6 months. The 2nd group of 280 patients (B--133, C--98, D+C--26, B+D--14; 172 men, 108 women, middle age of 35.9 ± 7.5 years) took only SAT. ALT, AST, bilirubin, γ-glutamiltranspeptidase, alkaline phosphatase levels, and blood analysis were evaluated. Due to UDCA normalization of the raised ALT and AST levels was observed by 6th week of SAT in 50 patients (from 80 patients with initially raised ALT and AST) of 1st group. ALT and AST levels reached norm in 1st group by 12th week whereas in 60 (21.4%) patients of 2nd group ALT, AST remained raised. Cholestasis remained at 30% of patients in the 1st group by the beginning of SAT and in 35.7% of patients in the 2nd. By 12th week cholestasis was observed only at 3.3% of patients of 1st group (32.1%--in the 2nd group). By 24th week the raised level of bilirubin remained in 7.1 % of patients in the 2nd group whereas in 1st group cholestasis was only at 1 patient. Decrease of hemoglobin level by 12th week of treatment within 110-100 g/l was observed at 10% of patients in 1 group, at 17.9%--in the 2nd. By 24th week anemia was observed only in 2nd group (1st group--0%; 2nd group--14.3%). Decrease in platelets level in the first 2 months of treatment was in both groups, but normalization of their quantity went earlier in 1st group. By 12th week of treatment level of platelets in all patients receiving UDCA was higher than 120,000/ml (3.6%--in the 2nd group). UDCA within SAT of hepatitis B and C allowed to reach the biochemical answer (ALT and AST level normalization) in earlier terms, and to better control of cholestasis. In UDCA group were less frequency of hematologic side effects of peginterferon and peginterferon+ribavirin.


Effect of marital satisfaction on self-regulation efforts in couples: Value of heart rate variability measurements.
This study explored self-regulatory efforts during the viewing of couple interactions and their association with relationship satisfaction. High-frequency heart rate variability (HF-HRV) was measured for each participant during a video recall of a recent couple interaction to quantify the self-regulatory processes governed by parasympathetic activity. Among 30 couples, HF-HRV was measured continuously during three specific periods to explore its change over time using a video-recall procedure: (1) resting state; (2) viewing of couple interactions (expressing daily life situations and conflictual interactions); and (3) recovery. Results of multilevel models revealed a u-shaped pattern of HF-HRV responses for men and women across the three periods with a nadir at the midway through the process. This pattern of physiological change (vagal suppression) reflects a flexible response to a stressful situation. Nevertheless, the pattern of physiological responses varied according to the level of relationship satisfaction. Men who were more satisfied in their couple relationship presented greater vagal suppression than dissatisfied men. In contrast, no significant HF-HRV changes were found in women over the different periods of the video-recall procedure and no moderating effect of relationship satisfaction. We discuss the different patterns of physiological responses observed both for men and women in terms of interindividual variability according to the level of their relationship satisfaction. The present study highlights the important role of relationship satisfaction in regulatory processes.


Morphine-induced stimulation of fetal breathing: role of mu 1-receptors and central muscarinic pathways.
The mechanism of action of low doses of morphine on breathing dynamics in the fetus was studied in 16 fetal lambs with chronically implanted electromyographic electrodes in the diaphragm. Morphine (0.15-2.5 mg/h) caused a significant dose-dependent increase in the number of diaphragmatic bursts per hour, with either an increase or no change in instantaneous breathing rate. There was also a significant dose-related increase in the continuity of the breathing pattern, as indicated by a decrease in the number of apneas per hour, and an increase in epoch duration. Morphine also had a significant effect on the stability of the breathing pattern, with an increase in the percentage of bursts that occurred in stable clusters. All of these effects were completely abolished by concurrent intracerebroventricular administration of either methylnaloxone or methylatropine or by pretreatment with intravenous naloxonazine. These results suggest that stimulation and stabilization of ventilatory activity in the fetal lamb by low doses of morphine are mediated via mu 1-receptors and involve central muscarinic pathways.