A statewide assessment of smoke-free policy in multiunit housing settings.
The prevalence of smoke-free policies in multiunit housing (MUH) in South Dakota was examined. Owner beliefs about smoke-free policies were identified. Stratified random sampling included 27 South Dakota counties classified as frontier, large rural, or urban. Data collection with MUH owners in selected counties employed a telephone survey with mailed backup. The owner response rate was 41.5% (324/780). A written smoke-free policy was reported by 175 (54.0%) owners, and 31 (10%) reported a verbal smoke-free policy. Owners in large rural counties (57.4%) had more written smoke-free policies than owners in urban (52.2%) and frontier (53.5%) counties. Only 8.5% of properties had policies covering both buildings and grounds. Owners without policies were more than twice as likely to manage U.S. Department of Housing and Urban Development subsidized units and were three times as likely to be current smokers. Owners without a smoke-free policy anticipated that a policy would decrease maintenance costs but increase turnover and vacancy rates. Nearly one-half (47.9%) of owners with no smoke-free policy had previously considered implementing a policy. Owners self-reported beliefs about smoke-free policies identified perceived benefits such as decreased maintenance and costs, improved tenant safety and health, and conscientious tenants. Perceived drawbacks included increased outdoor maintenance, enforcement problems, concerns about long-term tenants who smoke, and freedom/rights of smokers. This study provides a baseline assessment of smoke-free polices in MUH settings. Perceptions of owners without smoke-free policies focused on economic concerns that were inconsistent with reports from those owners with smoke-free policies.


Detection of Korean Native Honey and European Honey by Using Duplex Polymerase Chain Reaction and Immunochromatographic Assay.
Korean native honey (KNH) is much more expensive than European honey (EH) in Korea, because KNH is a favored honey which is produced less than EH. Food fraud of KNH has drawn attention of the government office concerned, which is in need of a method to differentiate between KNH and EH which are produced by the Asiatic honeybee, Apis cerana and the European honeybee, Apis mellifera, respectively. A method to discriminate KNH and EH was established by using duplex polymerase chain reaction (PCR) in this study. Immunochromatographic assay (IC) was examined to analyze the duplex PCR product. The DNA sequences of primers for the duplex PCR were determined by comparing cytochrome C oxidase genes of the two honey bee species. Chelex resin method was more efficient in extracting genomic DNA from honey than the other two procedures of commercial kits. The duplex PCR amplifying DNA of 133 bp were more sensitive than that amplifying DNA of 206 bp in detecting EH in the honey mixture of KNH and EH. Agarose gel electrophoresis and IC detected the DNA of 133 bp at the ratios of down to 1% and 5% EH in the honey mixture, respectively and also revealed that several KNH products distributed by internet shopping sites were actually EH. In conclusion, the duplex PCR with subsequent IC could also discriminate between KNH and EH and save time and labor.


Community violence and inpatient assaults: neurobiological deficits.
The goals of this study were to examine the relationship between community violence and inpatient assaults and to identify neurological and neuropsychological deficits underlying violent behavior. Thirty-three inpatients with a history of community violence were compared with 69 patients who did not have such a history. Inpatient assaults were recorded for 4 weeks; a neurological/neuropsychological battery was then administered. Patients without community violence were more likely to show transient or no violence while in the hospital. Patients with community violence performed more poorly on the Wisconsin Card Sorting Test and on psychomotor tasks, impairments that are consistent with frontal lobe dysfunction. Inpatient assaults were not associated with these neuropsychological impairments. They were related, however, to impairment on frontal motor programming tasks and a history of community violence.


Coherence and Consciousness: Study of Fronto-Parietal Gamma Synchrony in Patients with Disorders of Consciousness.
Evaluation of consciousness needs to be supported by the evidence of brain activation during external stimulation in patients with unresponsive wakefulness syndrome (UWS). Assessment of patients should include techniques that do not depend on overt motor responses and allow an objective investigation of the spontaneous patterns of brain activity. In particular, electroencephalography (EEG) coherence allows to easily measure functional relationships between pairs of neocortical regions and seems to be closely correlated with cognitive or behavioral measures. Here, we show the contribution of higher order associative cortices of patients with disorder of consciousness (N = 26) in response to simple sensory stimuli, such as visual, auditory and noxious stimulation. In all stimulus modalities an increase of short-range parietal and long-range fronto-parietal coherences in gamma frequencies were seen in the controls and minimally conscious patients. By contrast, UWS patients showed no significant modifications in the EEG patterns after stimulation. Our results suggest that UWS patients can not activate associative cortical networks, suggesting a lack of information integration. In fact, fronto-parietal circuits result to be connectively disrupted, conversely to patients that exhibit some form of consciousness. In the light of this, EEG coherence can be considered a powerful tool to quantify the involvement of cognitive processing giving information about the integrity of fronto-parietal network. This measure can represent a new neurophysiological marker of unconsciousness and help in determining an accurate diagnosis and rehabilitative intervention in each patient.


[Injuries of the major blood vessels in joint dislocations].
Experience with the treatment of 12 patients with injuries of major vessels resulting from dislocations of joints is generalized. In 5 of the patients an associated injury of nerve trunks was diagnosed, in 4 patients there were injuries of major veins. Reconstructive operations were made in 11 patients. In 8 patients full recovery was stated, three patients were subjected to amputation of the extremity. The main cause of the failure was late diagnosis of the closed trauma of the artery and progressing ischemia of the extremity.


Hormonal and renal effects of atrial natriuretic peptide in patients with secondary hypertension.
To investigate the involvement of atrial natriuretic peptide (ANP) in secondary hypertension, we examined hormonal and renal responses to ANP infusion (0.025 microgram/kg/min) in 27 patients with renal parenchymal hypertension, 10 with primary aldosteronism, 8 with renovascular hypertension, and 15 normotensive subjects. The preinfusion plasma concentration of ANP was significantly higher in patients with renal parenchymal hypertension (120 pg/ml, p less than 0.01) and in patients with primary aldosteronism (98 pg/ml, p less than 0.05) than in the normotensive subjects (40 pg/ml), but it was not greater than in the patients with renovascular hypertension (73 pg/ml, NS). In the patients with renal parenchymal hypertension, plasma ANP correlated negatively with creatinine clearance (r = -0.76, p less than 0.001). Mean blood pressure (-5%, p less than 0.01) and plasma aldosterone (-40%, p less than 0.001) decreased to a similar degree in the four groups during ANP infusion. However, an increase in urinary sodium excretion caused by ANP was higher in the hypertensive than in the normotensive patients (+250% vs. +70%, p less than 0.01) and correlated positively with mean blood pressure during ANP infusion (r = 0.47, p less than 0.001). The removal of adenomas in the patients with primary aldosteronism significantly lowered both plasma levels of ANP and cyclic guanosine 2',3'-monophosphate and reduced an increase in sodium excretion during ANP infusion, whereas the responses of blood pressure and plasma aldosterone to ANP infusion were not altered by the operation. Thus, these results suggest that elevated ANP secretion and increased natriuretic responses to ANP may modify the blood pressure and body fluid volume status in some types of secondary hypertension.


Preliminary characterization of a Mycobacterium abscessus mutant in human and murine models of infection.
The ability to persist in the host after the establishment of infection is an important virulence determinant for mycobacteria. Mycobacterium abscessus is a rapidly growing mycobacterial species which causes a variety of clinical syndromes in humans. We have obtained a rough, wild-type human clinical isolate of M. abscessus (M. abscessus-R) and a smooth, attenuated mutant (M. abscessus-S) which spontaneously dissociated from the clinical isolate. We have found that M. abscessus-R is able to persist and multiply in a murine pulmonary infection model in contrast to M. abscessus-S, which is rapidly cleared. To understand the basis for this difference, we characterized the behavior of these variants in human tissue culture models of infection. M. abscessus-R is able to persist and multiply in human monocytes, while M. abscessus-S is deficient in this ability. Both of these variants are phagocytized by human monocytes. M. abscessus-R resides in a phagosome typical for pathogenic mycobacteria with a tightly adherent phagosomal membrane. In contrast, M. abscessus-S resides in a "loose" phagosome with the phagosomal membrane separated from the bacterial cell wall. Both M. abscessus variants also have distinctive growth patterns in a recently described fibroblast-mycobacterium microcolony assay, with M. abscessus-R exhibiting growth characteristics similar to those previously reported for virulent M. tuberculosis and M. abscessus-S exhibiting growth characteristics similar to those previously reported for avirulent M. tuberculosis. In both the monocyte infection assay and the murine pulmonary infection model, numerous infected mononuclear phagocyte aggregates develop at sites of M. abscessus-R infection, but are absent with M. abscessus-S infection. We conclude that a mutation has occurred in the M. abscessus-S variant which has altered the ability of this organism to persist and multiply in host cells and that this may be related to the phenotypic changes we have observed in our tissue culture models of infection.


The two extremes of physiological tooth resorption in primary tooth with or without the permanent successor tooth.
Assessment of two radiographic images reveals two distinct, extreme situations of physiological tooth resorption, characteristic of primary teeth with or without permanent successor, due to partial anodontia. In all primary teeth, rhizolysis begins after the completion of formation, thanks to the apoptosis of their cells. When apoptosis induced by cementoblasts has denuded the root of these cells, the process of rhizolysis inevitably begins: This will be accelerated by mediators arising from the pericoronal follicle. When there is no permanent successor due to partial anodontia, rhizolysis occurs extremely slowly, and months later, without the epithelial rests of Malassez that were dead due to apoptosis, alveolodental ankylosis becomes established, and the tooth will gradually be replaced by bone, still within a physiological context. Rhizolysis and physiological tooth resorption may occur rapidly or slowly, early or late, and this depends on the presence of the permanent tooth, or its absence due to partial anodontia.


First case report of pulmonary and cutaneous nocardiosis caused by Nocardia mexicana in Iran.
Nocardia are aerobic partially acid-fast bacteria that are environmentally ubiquitous. This group of bacteria causes a rare bacterial infection of either the lungs (pulmonary) or body (systemic) that usually affects immunocompromised individuals. Nocardia mexicana was first isolated in 2004 from a patient with chronic bronchitis. However, there have been few reports on the clinical significance of this organism up to now. We herein report the first cases of N. mexicana in patients with pulmonary and cutaneous infection from Iran. A 57-year-old man was admitted to hospital due to a cutaneous wound on his left foot, fever, weakness, persistent cough and chest pain. At first, due to clinical examination and laboratory test, the patient was diagnosed as having tuberculosis. However, PCR of Mycobacterium tuberculosis was negative from broncho-alveolar lavage (BAL) samples. Direct PCR of BAL was performed for this patient and according to the clinical examinations and microbiological evaluations; the micro-organism was identified as N. mexicana and was isolated from both BAL and the wound. Finally, the patient was treated with linezolid and amikacin. The infections, with actinomycetes such as Nocardia , are easily neglected or misdiagnosed due to the fastidious nature of the organism and the inadequate microbiological experience of laboratories in the hospitals of developing countries. This case shows that hospitals should consider a better laboratory protocol to deal with the clinical cases in which fastidious organisms, and in particular Nocardia , are involved.


The distribution and chromatographic characterization of PHI (peptide histidine isoleucine amide)-27-like peptides in rat and porcine brain.
This study was initiated to characterize PHI (peptide histidine isoleucine amide)-27-like peptides (PLPs) in rat and porcine brain in comparison with other members of the vasoactive intestinal polypeptide (VIP) family and to investigate their distribution by radioimmunoassay. The peptidic nature of the rat brain PLP was indicated by its trypsin sensitivity. On Sephadex chromatography rat brain PLP has the same molecular weight as synthetic (porcine intestinal) PHI-27. High pressure liquid chromatographic separations revealed that PLP in rat and porcine brain extracts elutes as a single peak distinct from VIP or secretin. Porcine brain PLP elutes in the same position as synthetic PHI-27, whereas rat brain PLP immunoreactivity consistently separates from synthetic PHI-27. This suggests that porcine brain PLP is identical to synthetic PHI-27, in agreement with the reported sequence of Tatemoto et al. (Tatemoto, K., M. Carlquist, T. McDonald, and V. Mutt (1983) FEBS Lett. 153: 248-252), whereas PLP may have a different amino acid sequence (or may be post-translationally modified). Using specific PHI and VIP radioimmunoassays, the distribution of PLP was found to parallel that of VIP in rat and porcine brain, being highest in cerebral cortex, amygdala, and hippocampus. PLP, like VIP, is abundant in rat retina and can be included in the growing list of retinal peptides. This highly correlated distribution of VIP and PLP may be explained by the recent discovery that they are derived from the same precursor (Itoh, N., K. Obata, N. Yanaihara, and H. Okamoto (1983) Nature 304: 547-549).(ABSTRACT TRUNCATED AT 250 WORDS)


Differential immunogenicity of BNT162b2 or ChAdOx1 vaccines after extended-interval homologous dual vaccination in older people.
Several SARS-CoV-2 vaccines have shown clinical efficacy against Covid-19 infection but there remains uncertainty about the immune responses elicited by different regimens. This is a particularly important question for older people who are at increased clinical risk following infection and in whom immune senescence may limit vaccine responses. The BNT162b2 mRNA and ChAdOx1 adenovirus vaccines were the first two vaccines deployed in the UK programme using an 8-12 week 'extended interval'. We undertook analysis of the spike-specific antibody and cellular immune response in 131 participants aged 80+ years after the second dose of 'extended interval' dual vaccination with either BNT162b2 mRNA (n = 54) or ChAdOx1 (n = 77) adenovirus vaccine. Blood samples were taken 2-3 weeks after second vaccine and were paired with samples taken at 5-weeks after first vaccine which have been reported previously. Antibody responses were measured using the Elecsys® electrochemiluminescence immunoassay assay and cellular responses were assessed by IFN-γ ELISpot. Antibody responses against spike protein became detectable in all donors following dual vaccination with either vaccine. 4 donors had evidence of previous natural infection which is known to boost vaccine responses. Within the 53 infection-naïve donors the median antibody titre was 4030 U/ml (IQR 1892-8530) following BNT162b2 dual vaccination and 1405 (IQR 469.5-2543) in the 74 patients after the ChAdOx1 vaccine (p = < 0.0001). Spike-specific T cell responses were observed in 30% and 49% of mRNA and ChAdOx1 recipients respectively and median responses were 1.4-times higher in ChAdOx1 vaccinees at 14 vs 20 spots/million respectively (p = 0.022). Dual vaccination with BNT162b2 or ChAdOx1 induces strong humoral immunity in older people following an extended interval protocol. Antibody responses are 2.9-times higher following the mRNA regimen whilst cellular responses are 1.4-times higher with the adenovirus-based vaccine. Differential patterns of immunogenicity are therefore elicited from the two vaccine platforms. It will be of interest to assess the relative stability of immune responses after these homologous vaccine regimens in order to assess the potential need for vaccine boosting. Furthermore, these findings indicate that heterologous vaccine platforms may offer the opportunity to further optimize vaccine responses.


Predicting optimal treatment outcomes in phase-based treatment and direct trauma-focused treatment among patients with posttraumatic stress disorder stemming from childhood abuse.
Research over the last few decades has demonstrated the effectiveness of various treatments for posttraumatic stress disorder (PTSD). However, the question of which treatment works best remains, especially for patients with PTSD stemming from childhood abuse. Using the Personalized Advantage Index (PAI), we explored which patients benefit more from phase-based treatment and which benefit more from direct trauma-focused treatment. Data were obtained from a multicenter randomized controlled trial (RCT) comparing a phase-based treatment condition (i.e., eye-movement desensitization and reprocessing [EMDR] therapy preceded by Skills Training in Affect and Interpersonal Regulation [STAIR]; n = 57) and a direct trauma-focused treatment (EMDR only; n = 64) among individuals with PTSD related to childhood abuse. Machine learning techniques were used to examine all pretreatment variables included in the trial as potential predictors and moderators, with selected variables combined to build the PAI model. The utility of the PAI was tested by comparing actual posttreatment outcomes of individuals who received PAI-indicated treatment with those allocated to a non-PAI-indicated treatment. Although eight pretreatment variables between PTSD treatment outcome and treatment condition were selected as moderators, there was no significant difference between participants assigned to their PAI-indicated treatment and those randomized to a non-PAI-indicated treatment, d = 0.25, p = .213. Hence, the results of this study do not support the need for personalized medicine for patients with PTSD and a history of childhood abuse. Further research with larger sample sizes and external validation is warranted.


Age-related uterotrophic response of soy isoflavone intake in rats.
This study investigated the effects of soy isoflavone intake on uterotrophic responses in growing (juvenile) and adult female rats. In the growing rats, feed intake showed a decreasing trend as the level of dietary isoflavones increased to 0.02%, 0.1%, and 0.2% of the diets. However, in the case of the adult rats there were no significant differences among groups. Weight gains were significantly lower in the rats fed 0.1% and 0.2% isoflavones than the controls in both juvenile and adult rats. The urinary excretion of daidzein and genistein was significantly increased with increasing levels of dietary isoflavones. The calculated urinary recoveries of daidzein and genistein were significantly lower in the groups fed 0.1% and 0.2% isoflavones compared to the juvenile and adult rat groups fed 0.02% isoflavones; no significant difference was observed between the 0.1% and 0.2% groups. The calculated urinary recoveries of daidzein and genistein in the adult rats were significantly higher than in the juvenile rats. The differences in the urinary recoveries between ages may be due to greater availability of the isoflavones in the adult rats. Isoflavone supplementation did not alter the histological phenotype of endometrial cells in growing rats, but a hyperplastic response of endometrium was shown in the adult rats. Dietary isoflavones, therefore, may not have an estrogenic effect on the uterus at these dose levels during the growth period, but this organ would be expected to be a likely target for isoflavone action in adults. We observed in the present study that isoflavones are more bioavailable in adult rats than in the juvenile rats. Therefore, soy isoflavone supplementation may not act as an endocrine disrupter during the growth period but may exert a phytoestrogenic effect on the uterus of adult rats.


CA-125 in women with endometriosis.
The serum CA-125 level is elevated in most women with endometriosis. Although tests are readily available to measure the marker, simple modifications of the present assays are required to improve and standardize the quality of the measurements. The serum test has low sensitivity and would not be appropriate for general screening purposes, but in clinical situations that have a relatively high prevalence of endometriosis, CA-125 determinations have acceptable sensitivities and very high specificities. The concentrations of CA-125 correlate with both the severity and the clinical course of the disease. In women with diagnosed endometriosis, use of serial CA-125 determinations to monitor the course of the disease shows much promise in early studies. The changes in the CA-125 levels can offer additional information to the clinician about the status of the endometriosis, but how much this information will assist in the management and improve the outcome of treatment must await the results of prospective studies.


Adaptation: a concept analysis.
The concept of adaptation is historically evident in nursing practice. Florence Nightingale showed how the environment required adaptation to meet the needs of the patient. Following her lead, several nurse theorists developed models with examples of the concept of adaptation: the nurse either adapts to the patient's needs, works to help the patient adapt to the environment, or adapts the environment to the needs of the patient. Sr. Callista Roy's Adaptation Model of Nursing is one such nursing model. Although this model has been applied in many clinical and administrative areas, the use of the concept in a school setting with special-need's student requires additional definition and clarification. The goal of this concept analysis paper is to clarify and explore the definition of adaptation in the school setting with application to an Individualized Healthcare Plan (IHP).


Feasibility of a tailored intervention to improve preventive care use in women.
Women age 50 years and older are in need of multiple preventive health care services. Despite recent improvements in rates of delivery of preventive care services, especially within managed care organizations, substantial numbers of women are still being underscreened. Efforts to improve delivery of preventive care services have often focused on one outstanding service despite the fact that patients often are in need of many services. A total of 893 women age 50 to 55 years were mailed a self-administered survey to identify outstanding preventive health care service needs. Patients in need of three or more outstanding preventive health care services were identified from survey respondents to participate in a feasibility study evaluating a tailored, customized intervention called Tic Tac Health. Five-hundred ninety-one women returned the survey (67%). Four-hundred forty-eight (76%) women were in need of one or more preventive health services; 92 (16%) were in need of three or more. Twenty-two patients (24%) completed the Tic Tac Health card. The women who completed the card were similar to those who did not. Despite documented physician visits, presence of managed care health insurance, and a designated primary care provider, a significant number of women are still in need of multiple preventive health services. An intervention targeting multiple preventive health services was demonstrated to be both feasible and effective. Further evaluation via a randomized controlled trial should be conducted to determine if an intervention like Tic Tac Health would be an effective modality for improving rates of receipt of multiple preventive health care services.


Setting up a cohort study in speech and language therapy: lessons from The UK Cleft Collective Speech and Language (CC-SL) study.
Efforts to increase the evidence base in speech and language therapy are often limited by methodological factors that have restricted the strength of the evidence to the lower levels of the evidence hierarchy. Where higher graded studies, such as randomized controlled trials, have been carried out, it has sometimes been difficult to obtain sufficient power to detect a potential effect of intervention owing to small sample sizes or heterogeneity in the participants. With certain clinical groups such as cleft lip and palate, systematic reviews of intervention studies have shown that there is no robust evidence to support the efficacy of any one intervention protocol over another. To describe the setting up of an observational clinical cohort study and to present this as an alternative design for answering research questions relating to prevalence, risk factors and outcomes from intervention. The Cleft Collective Speech and Language (CC-SL) study is a national cohort study of children born with cleft palate. Working in partnership with regional clinical cleft centres, a sample size of over 600 children and 600 parents is being recruited and followed up from birth to age 5 years. Variables being collected include demographic, psychological, surgical, hearing, and speech and language data. The process of setting up the study has led to the creation of a unique, large-scale data set which is available for researchers to access now and in future. As well as exploring predictive factors, the data can be used to explore the impact of interventions in relation to individual differences. Findings from these investigations can be used to provide information on sample criteria and definitions of intervention and dosage which can be used in future trials. The observational cohort study is a useful alternative design to explore questions around prevalence, risk factors and intervention for clinical groups where robust research data are not yet available. Findings from such a study can be used to guide service-delivery decisions and to determine power for future clinical trials.


Integrity of Neuronal Size in the Entorhinal Cortex Is a Biological Substrate of Exceptional Cognitive Aging.
Average aging is associated with a gradual decline of memory capacity. SuperAgers are humans ≥80 years of age who show exceptional episodic memory at least as good as individuals 20-30 years their junior. This study investigated whether neuronal integrity in the entorhinal cortex (ERC), an area critical for memory and selectively vulnerable to neurofibrillary degeneration, differentiated SuperAgers from cognitively healthy younger individuals, cognitively average peers ("Normal Elderly"), and individuals with amnestic mild cognitive impairment. Postmortem sections of the ERC were stained with cresyl violet to visualize neurons and immunostained with mouse monoclonal antibody PHF-1 to visualize neurofibrillary tangles. The cross-sectional area (i.e., size) of layer II and layer III/V ERC neurons were quantified. Two-thirds of total participants were female. Unbiased stereology was used to quantitate tangles in a subgroup of SuperAgers and Normal Elderly. Linear mixed-effect models were used to determine differences across groups. Quantitative measurements found that the soma size of layer II ERC neurons in postmortem brain specimens were significantly larger in SuperAgers compared with all groups (p < 0.05)-including younger individuals 20-30 years their junior (p < 0.005). SuperAgers had significantly fewer stereologically quantified Alzheimer's disease-related neurofibrillary tangles in layer II ERC than Normal Elderly (p < 0.05). This difference in tangle burden in layer II between SuperAgers and Normal Elderly suggests that tangle-bearing neurons may be prone to shrinkage during aging. The finding that SuperAgers show ERC layer II neurons that are substantially larger even compared with individuals 20-30 years younger is remarkable, suggesting that layer II ERC integrity is a biological substrate of exceptional memory in old age.SIGNIFICANCE STATEMENT Average aging is associated with a gradual decline of memory. Previous research shows that an area critical for memory, the entorhinal cortex (ERC), is susceptible to the early formation of Alzheimer's disease neuropathology, even during average (or typical) trajectories of aging. The Northwestern University SuperAging Research Program studies unique individuals known as SuperAgers, individuals ≥80 years old who show exceptional memory that is at least as good as individuals 20-30 years their junior. In this study, we show that SuperAgers harbor larger, healthier neurons in the ERC compared with their cognitively average same-aged peers, those with amnestic mild cognitive impairment, and - remarkably - even compared with individuals 20-30 years younger. We conclude that larger ERC neurons are a biological signature of the SuperAging trajectory.


Prediction of flunixin tissue residue concentrations in livers from diseased cattle.
Flunixin, a widely used non-steroidal anti-inflammatory drug, was a leading cause of violative residues in cattle. The objective of this analysis was to explore how the changes in pharmacokinetic (PK) parameters that may be associated with diseased animals affect the predicted liver residue of flunixin in cattle. Monte Carlo simulations for liver residues of flunixin were performed using the PK model structure and relevant PK parameter estimates from a previously published population PK model for flunixin in cattle. The magnitude of a change in the PK parameter value that resulted in a violative residue issue in more than one percent of a cattle population was compared. In this regard, elimination clearance and volume of distribution affected withdrawal times. Pathophysiological factors that can change these parameters may contribute to the occurrence of violative residues of flunixin.


Economic crisis and suicidal behaviour: the role of unemployment, sex and age in Andalusia, southern Spain.
Although suicide rates have increased in some European countries in relation to the current economic crisis and austerity policies, that trend has not been observed in Spain. This study examines the impact of the economic crisis on suicide attempts, the previously neglected endpoint of the suicidal process, and its relation to unemployment, age and sex. The study was carried out in Andalusia, the most populated region of Spain, and which has a high level of unemployment. Information on suicide attempts attended by emergency services was extracted from the Health Emergencies Public Enterprise Information System (SIEPES). Suicide attempts occurring between 2003 and 2012 were included, in order to cover five years prior to the crisis (2003-2007) and five years after its onset (2008-2012). Information was retrieved from 24,380 cases (11,494 men and 12,886 women) on sex, age, address, and type of attention provided. Age-adjusted suicide attempt rates were calculated. Excess numbers of attempts from 2008 to 2012 were estimated for each sex using historical trends of the five previous years, through time regression models using negative binomial regression analysis. To assess the association between unemployment and suicide attempts rates, linear regression models with fixed effects were performed. A sharp increase in suicide attempt rates in Andalusia was detected after the onset of the crisis, both in men and in women. Adults aged 35 to 54 years were the most affected in both sexes. Suicide attempt rates were associated with unemployment rates in men, accounting for almost half of the cases during the five initial years of the crisis. Women were also affected during the recession period but this association could not be specifically attributed to unemployment. This study enhances our understanding of the potential effects of the economic crisis on the rapidly increasing suicide attempt rates in women and men, and the association of unemployment with growing suicidal behaviour in men. Research on the suicide effects of the economic crisis may need to take into account earlier stages of the suicidal process, and that this effect may differ by age and sex.


Exisulind Cell Pathways.
Cell Pathways has developed exisulind (Aptosyn), an oral apoptosis modulator and cGMP phosphodiesterase inhibitor, for the potential treatment of several oncologic indications including precancerous adenomatous polyposis coli (APC), also known as familial adenomatous polyposis (FAP), precancerous sporadic colonic polyps, cervical dysplasia and the prevention of tumor recurrence in prostate and breast cancer. An NDA filing for the treatment of precancerous APC, for which the US FDA designated exisulind a Fast Track product in July 1998, was initially expected in March 1999 [291313]. However, in January of the same year the company stated that it anticipated a delay in the NDA filing. The decision was based on unsatisfactory phase III data [308912], [313124]. In June 1999, the company completed analysis of the phase III trial data [328000] and the NDA was submitted in August 1999. An NDA was accepted for review by the FDA in October 1999 for the treatment of APC [328000], [338007], [344721], after data from three additional trials were submitted to the FDA in support of the NDA. At this time phase II/III trials were also ongoing for prostate and breast cancer recurrence [287250], [326795]. Approval for the indication of FAP had been expected by the end of 2000 [365737] but in September 2000 the FDA completed its initial review and advised Cell Pathways that exisulind will not be approved at this time. Cell Pathways has received a 'non-approvable' letter and intends to advise the FDA of its intent to amend the NDA and to request a meeting to address the deficiencies in the NDA [383249], [383560]. The first of the three additional trials submitted to the FDA in October 1999 was a 6-month, open-label trial involving 48 of the patients who completed a phase II/III study of exisulind in early 1999. After 6 months of treatment with exisulind, 25 patients who had previously been taking placebo experienced a 50% reduction in polyp formation. The patients continuing treatment with exisulind exhibited a further 50% reduction from their already reduced rate of polyp formation [344991]. The second study was an extension study of 11 patients who participated in a 6-month, open-label, phase I/II, dose-ranging, safety and efficacy trial. As of October 1999, these patients were still on therapy and had been receiving exisulind for between 36 and 50 months. They had all experienced statistically significant reductions in polyp formation rates [344991]. The third study was a double-blind, placebo-controlled safety study of 26 patients. All patients exhibited a trend of reduced new polyp formation when compared to placebo. Exisulind was generally well-tolerated by all patients during the course of the studies [344991]. In July 2000, Cell Pathways signed a marketing and distribution agreement for Canada with Paladin Labs, allowing Paladin exclusive rights to commercialize exisulind within Canada [376072]. Also in July 2000, Cell Pathways announced that patents covering methods of identifying compounds that selectively stimulate apoptosis have been allowed in Europe and Japan. The patents describe the mechanism of action of Cell Pathways' SAANDs, including exisulind, and use of that knowledge in screening for new drugs [374888]. In January 1999, the company received US-05858694 covering the mechanism of action of exisulind [311504].


Seeing "what" through "why": Evidence from probing the causal structure of hierarchical motion.
Although our world is hierarchically organized, the perception, attention, and memory of hierarchical structures remain largely unknown. The current study shows how a hierarchical motion representation enhances the inference of an object's position in a dynamic display. The motion hierarchy is formed as an acyclic tree in which each node represents a distinctive motion component. Each individual object is instantiated as a node in the tree. In a position inference task, participants were asked to infer the position of a target object, given how it moved jointly with other objects. The results showed that the inference is supported by the context formed by nontarget objects. More importantly, this contextual effect is (a) structured, with stronger support from objects forming a hierarchical tree than from those moving independently; (b) degreed, with stronger support from objects closer to the target in the motion tree; and (c) directed, with stronger support from the target's ancestor nodes than from its descendent nodes. Computational modeling results further indicated that the contextual effect cannot be explained by correlated and contingent movements without an explicit causal representation of the motion hierarchy. Together, these studies suggest that human vision is a type of intelligence, which sees what are in the dynamic displays by recovering why and how they are generated. (PsycINFO Database Record


Integration of HIV care into maternal health services: a crucial change required in improving quality of obstetric care in countries with high HIV prevalence.
The failure to reduce preventable maternal deaths represents a violation of women's right to life, health, non-discrimination and equality. Maternal deaths result from weaknesses in health systems: inadequate financing of services, poor information systems, inefficient logistics management and most important, the lack of investment in the most valuable resource, the human resource of health workers. Inadequate senior leadership, poor communication and low staff morale are cited repeatedly in explaining low quality of healthcare. Vertical programmes undermine other service areas by creating competition for scarce skilled staff, separate reporting systems and duplication of training and tasks. Confidential enquiries and other quality-improvement activities have identified underlying causes of maternal deaths, but depend on the health system to respond with remedies. Instead of separate vertical programmes for management of HIV, tuberculosis, and reproductive health, integration of care and joint management of pregnancy and HIV would be more effective. Addressing health system failures that lead to each woman's death would have a wider impact on improving the quality of care provided in the health service as a whole. More could be achieved if existing resources were used more effectively. The challenge for African countries is how to get into practice interventions known from research to be effective in improving quality of care. Advocacy and commitment to saving women's lives are crucial elements for campaigns to influence governments and policy -makers to act on the findings of these enquiries. Health professional training curricula should be updated to include perspectives on patients' rights, communication skills, and integrated approaches, while using adult learning methods and problem-solving techniques. In countries with high rates of Human Immunodeficiency Virus (HIV), indirect causes of maternal deaths from HIV-associated infections now exceed direct causes of hemorrhage, hypertension and sepsis. Advocacy for all pregnant HIV-positive women to be on anti-retroviral therapy must extend to improvements in the quality of service offered, better organised obstetric services and integration of clinical HIV care into maternity services. Improved communication and specialist support to peripheral facilities can be facilitated through advances in technology such as mobile phones.


Exenatide Once Weekly for Management of Type 2 Diabetes: A Review.
Exenatide is one of the exendin-based glucagon-like peptide 1 receptor agonists (GLP-1RAs) and is currently available in two formulations, ie, exenatide twice daily (BID), a short-acting GLP-1RA, and exenatide once weekly (QW), a long-acting GLP-1RA. Clinical efficacy and safety of exenatide 2 mg QW in patients with type 2 diabetes (T2DM) has been demonstrated in the DURATION study program. Exenatide QW has been shown to achieve greater HbA1c reduction compared with exenatide BID, with less injection frequency and greater treatment satisfaction. However, exenatide QW failed to show a significant cardiovascular risk reduction in a cardiovascular outcome trial (CVOT), the EXSCEL trial, while other GLP-1RAs have shown positive CV outcomes. Furthermore, exenatide QW has been shown to be inferior to liraglutide and semaglutide with respect to HbA1c or body weight reduction in the head-to-head trials. Thus, although the long-term efficacy and safety of exenatide QW have been demonstrated, exenatide QW might be selected with lower priority within the class of GLP1-RAs for the management of T2DM, especially for patients at high CV risk. On the other hand, exenatide QW is now expected to be a treatment option for children with T2DM or patients with Parkinson's disease. This review provides an overview of the current evidence regarding the clinical efficacy and safety of exenatide QW and discusses the current perspectives on exenatide QW for treatment of T2DM.


Multilevel analysis of solar radiation and cancer mortality using ecological data in Japan.
A preventive effect of solar radiation on cancer has been suspected. This study aimed to compare the statistical relationship between solar radiation and cancer mortality according to hierarchical models and adjustment for confounding factors, and then to demonstrate the relationship with main site-specific cancer mortalities in Japan. We examined the relationship between all-site and main site-specific cancer mortalities and global solar radiation using Poisson regression with municipal data around 2000. The models included single-level (municipality) and multilevel (municipality and prefecture) with/without potential confounding factors (lifestyle and socioeconomic variables). For all-site cancer, single-level analysis showed a significant, strong negative association with solar radiation. However, multilevel analysis showed a moderate or no association. In multilevel analysis with potential confounding factors, solar radiation was significantly negatively associated with most site-specific cancers, but not with gallbladder and liver cancer in men and stomach and breast cancer in women. Our findings support the preventive effective of solar radiation on several types of cancer. However, to show a concrete relationship, a statistical model with an appropriate hierarchy and adjustment for potential confounding factors is required.


Contact sensitization to modern wound dressings in 70 patients with chronic leg ulcers.
Patients with chronic leg ulcers typically experience contact allergy to topical treatments. Although declared as hypoallergenic, modern wound dressings have caused several reported cases of contact allergy. The aim of the study was to evaluate any allergenic potential of modern wound dressings in patients with leg ulcers. Seventy-one patients were included in our prospective observation. Patch tests were performed with a selection of 10 modern wound dressings and with selected allergens according to series of the German Contact Dermatitis Research Group (DKG). Of 70 patients eligible for evaluation, 12 (17%) were positive for the hydrogel NuGel, followed by the hydrocolloid NuDerm (n = 7/70, 10%) and the ionic silver-containing wound dressing Aquacel Ag and the gauze Adaptic (both n = 4/70, 5%). Patients with recalcitrant ulcers of prolonged duration showed a significant higher number of epicutaneous sensitizations to wound dressings than patients with shorter ulcer duration. The allergenic potential of modern wound dressings should not be underestimated. There is need for precise declaration of all ingredients.


Epiphyte response to drought and experimental warming.
The high diversity and abundance of vascular epiphytes in tropical montane cloud forest is associated with frequent cloud immersion, which is thought to protect plants from drought stress. Increasing temperature and rising cloud bases associated with climate change may increase epiphyte drought stress, leading to species and biomass loss. We tested the hypothesis that warmer and drier conditions associated with a lifting cloud base will lead to increased mortality and/or decreased recruitment of epiphyte ramets, altering species composition in epiphyte mats. By using a reciprocal transplant design, where epiphyte mats were transplanted across an altitudinal gradient of increasing cloud immersion, we differentiated between the effects of warmer and drier conditions from the more general prediction of niche theory that transplanting epiphytes in any direction away from their home elevation should result in reduced performance. Ramet mortality increased, recruitment decreased, and population size declined for epiphytes in mats transplanted down slope from the highest elevation, into warmer and drier conditions, but epiphytes from lower elevations showed greater resistance to drought in all treatments. Epiphyte community composition changed with elevation, but over the timescale of the experiment there were no consistent changes in species composition. Our results suggest some epiphytes may show resistance to climate change depending on the environmental context, although if climate change results in consistently drier conditions and higher cloud bases, biomass loss and shifting species composition in epiphyte communities is likely.


Mutations affecting regulation of methionine biosynthetic genes isolated by use of met-lac fusions.
Fusions of the lac genes to the promoters of four structural genes in the methionine biosynthetic pathway, metA, metB, metE, and metF, were obtained by the use of the Mu d(Ap lac) bacteriophage. The levels of beta-galactosidase in these strains could be derepressed by growth under methionine-limiting conditions. Furthermore, growth in the presence of vitamin B12 repressed the synthesis of beta-galactosidase in strains containing a fusion of lacZ to the metE promoter, phi(metE'-lacZ+). Mutations affecting the regulation of met-lac fusions were generated by the insertion of Tn5. Tn5 insertions were obtained at the known regulatory loci metJ and metK. Interestingly, a significant amount of methionine adenosyltransferase activity remained in the metK mutant despite the fact that the mutation was generated by an insertion. Several Tn5-induced regulatory mutations were isolated by screening for high-level beta-galactosidase expression in a phi(metE'-lacZ+) strain in the presence of vitamin B12. Tn5 insertions mapping at the btuB (B12 uptake), metH (B12 dependent tetrahydropteroylglutamate methyltransferase), and metF (5,10-methylenetetrahydrofolate reductase) loci were obtained. The isolation of the metH mutant was consistent with previous suggestions that the metH gene product is required for the repression of metE by vitamin B12. The metF::Tn5 insertion was of particular interest since it suggested that a functional metf gene product was also needed for repression of metE by vitamin B12.


Infrared spectra and anharmonic coupling of proton-bound nitrogen dimers N2-H+-N2, N2-D+-N2, and 15N2-H+-15N2 in solid para-hydrogen.
The proton-bound nitrogen dimer, N2-H+-N2, and its isotopologues were investigated by means of vibrational spectroscopy. These species were produced upon electron bombardment of mixtures of N2 (or 15N2) and para-hydrogen (p-H2) or normal-D2 (n-D2) during deposition at 3.2 K. Reduced-dimension anharmonic vibrational Schrödinger equations were constructed to account for the strong anharmonic effects in these protonated species. The fundamental lines of proton motions in N2-H+-N2 were observed at 715.0 (NH+N antisymmetric stretch, ν4), 1129.6 (NH+N bend, ν6), and 2352.7 (antisymmetric NN/NN stretch, ν3) cm-1, in agreement with values of 763, 1144, and 2423 cm-1 predicted with anharmonic calculations using the discrete-variable representation (DVR) method at the CCSD/aug-cc-pVDZ level. The lines at 1030.2 and 1395.5 cm-1 were assigned to combination bands involving nν2 + ν4 (n = 1 and 2) according to theoretical calculations; ν2 is the N2N2 stretching mode. For 15N2-H+-15N2 in solid p-H2, the corresponding major lines were observed at 710.0 (ν4), 1016.7 (ν2 + ν4), 1124.3 (ν6), 1384.8 (2ν2 + ν4), and 2274.9 (ν3) cm-1. For N2-D+-N2 in solid n-D2, the corresponding major lines were observed at 494.0 (ν4), 840.7 (ν2 + ν4), 825.5 (ν6), and 2356.2 (ν3) cm-1. In addition, two lines at 762.0 (weak) and 808.3 cm-1 were tentatively assigned to be some modes of N2-H+-N2 perturbed or activated by a third N2 near the proton.


Assessing gender responsiveness of COVID-19 response plans for populations in conflict-affected humanitarian emergencies.
The COVID-19 pandemic has necessitated rapid development of preparedness and response plans to quell transmission and prevent illness across the world. Increasingly, there is an appreciation of the need to consider equity issues in the development and implementation of these plans, not least with respect to gender, given the demonstrated differences in the impacts both of the disease and of control measures on men, women, and non-binary individuals. Humanitarian crises, and particularly those resulting from conflict or violence, exacerbate pre-existing gender inequality and discrimination. To this end, there is a particularly urgent need to assess the extent to which COVID-19 response plans, as developed for conflict-affected states and forcibly displaced populations, are gender responsive. Using a multi-step selection process, we identified and analyzed 30 plans from states affected by conflict and those hosting forcibly displaced refugees and utilized an adapted version of the World Health Organization's Gender Responsive Assessment Scale (WHO-GRAS) to determine whether existing COVID-19 response plans were gender-negative, gender-blind, gender-sensitive, or gender-transformative. We find that although few plans were gender-blind and none were gender-negative, no plans were gender-transformative. Most gender-sensitive plans only discuss issues specifically related to women (such as gender-based violence and reproductive health) rather than mainstream gender considerations throughout all sectors of policy planning. Despite overwhelming evidence about the importance of intentionally embedding gender considerations into the COVID-19 planning and response, none of the plans reviewed in this study were classified as 'gender transformative.' We use these results to make specific recommendations for how infectious disease control efforts, for COVID-19 and beyond, can better integrate gender considerations in humanitarian settings, and particularly those affected by violence or conflict.


Recent Advances in Folates and Autoantibodies against Folate Receptors in Early Pregnancy and Miscarriage.
Though firstly identified in cerebral folate deficiency, autoantibodies against folate receptors (FRAbs) have been implicated in pregnancy complications such as miscarriage; however, the underlying mechanism needs to be further elaborated. FRAbs can be produced via sensitization mediated by folate-binding protein as well as gene mutation, aberrant modulation, or degradation of folate receptors (FRs). FRAbs may interfere with folate internalization and metabolism through blocking or binding with FRs. Interestingly, different types of FRs are expressed on trophoblast cells, decidual epithelium or stroma, and macrophages at the maternal-fetal interface, implying FRAbs may be involved in the critical events necessary for a successful pregnancy. Thus, we propose that FRAbs may disturb pregnancy establishment and maintenance by modulating trophoblastic biofunctions, placental development, decidualization, and decidua homeostasis as well as the functions of FOLR2+ macrophages. In light of these findings, FRAbs may be a critical factor in pathological pregnancy, and deserve careful consideration in therapies involving folic acid supplementation for pregnancy complications.


Cognitive reserve modulates functional brain responses during memory tasks: a PET study in healthy young and elderly subjects.
Cognitive reserve (CR) is the ability of an individual to cope with advancing brain pathology so that he remains free of symptomatology. Epidemiological evidence and in vivo neurometabolic data suggest that CR may be mediated through education or IQ. The goal of this study was to investigate CR-mediated differential brain activation in 17 healthy young adults and 19 healthy elders. Using nonquantitative H(2)(15)O PET scanning, we assessed relative regional cerebral blood flow while subjects performed a serial recognition memory task under two conditions: nonmemory control (NMC), in which one shape was presented in each study trial; and titrated demand (TD), in which study list length was adjusted so that each subject recognized shapes at approximately 75% accuracy. A factor score that summarized years of education and scores on two IQ indices was used as an index of CR. Voxel-wise, multiple regression analyses were performed with TD minus NMC difference PET counts as the dependent variable and the CR variable as the independent variable of interest. We identified brain regions where regression slopes were different from zero in each separate group, and also those where regression slopes differed between the two age groups. The slopes were significantly more positive in the young in the right inferior temporal gyrus, right postcentral gyrus, and cingulate, while the elderly had a significantly more positive slope in left cuneus. Brain regions where systematic relationships between CR and brain activation differ as a function of aging are loci where compensation for aging has occurred. They may mediate differential ability to cope with brain changes in aging.


Effect of ultrafiltration on thermal variables, skin temperature, skin blood flow, and energy expenditure during ultrapure hemodialysis.
The cause of the increase in core temperature (CT) during hemodialysis (HD) is still under debate. It has been suggested that peripheral vasoconstriction as a result of hypovolemia, leading to a reduced dissipation of heat from the skin, is the main cause of this increase in CT. If so, then it would be expected that extracorporeal heat flow (Jex) needed to maintain a stable CT (isothermic; T-control = 0, no change in CT) is largely different between body temperature control HD combined with ultrafiltration (UF) and body temperature control HD without UF (isovolemic). Consequently, significant differences in DeltaCT would be expected between isovolemic HD and HD combined with UF at zero Jex (thermoneutral; E-control = 0, no supply or removal of thermal energy to and from the extracorporeal circulation). During the latter treatment, the CT is expected to increase. In this study, changes in thermal variables (CT and Jex), skin blood flow, energy expenditure, and cytokines (TNF-alpha, IL-1 receptor antagonist, and IL-6) were compared in 13 patients, each undergoing body temperature control (T-control = 0) HD without and with UF and energy-neutral (E-control = 0) HD without and with UF. CT increased equally during energy-neutral treatments, with (0.32 +/- 0.16 degrees C; P = 0.000) and without (0.27 +/- 0.29 degrees C; P = 0.006) UF. In body temperature control treatments, the relationship between Jex and UF tended to be significant (r = -0.51; P = 0.07); however, there was no significant difference in cooling requirements regardless of whether treatments were done without (-17.9 +/- 9.3W) or with UF (-17.8 +/- 13.27W). Changes in energy expenditure did not differ among the four treatment modes. There were no significant differences in pre- and postdialysis levels of cytokines within or between treatments. Although fluid removal has an effect on thermal variables, no single mechanism seems to be responsible for the increased heat accumulation during HD.


Number of Surgical Procedures for Patients With Cleft lip and Palate From Birth to 21 Years Old at a Single Children's Hospital.
Pediatric patients with cleft lip and palate undergo numerous surgeries throughout their childhood and early adulthood to correct the aesthetic and functional stigmata of their diagnoses. This study identifies patient and clinical factors that contribute to the number of surgeries and anesthesia events children undergo for their cleft repair. Retrospective chart review was performed using the genetic and dysmorphology database at Rady Children's Hospital San Diego. All patients with cleft lip or cleft palate diagnosis who underwent surgery at Rady Children's Hospital San Diego between 1988 and 2014 were included. A sample size of 71 patients was analyzed. Poisson regression was used to determine if there is a relationship between each variable of interest and the number of procedures. For our sample of 71 patients, the average number of surgical procedures was 8.6 (SD, 4.4). The average number of anesthesia events was 6.7 (SD, 3.3). Across and within diagnosis, race and sex were not statistically significant factors in patients' number of surgeries. Patients with bilateral cleft lip and palate (BCLP) and unilateral cleft lip and palate had, on average, 10 and 9.4 procedures, respectively. This is in contrast to patients with unilateral cleft lip and isolated cleft palate who had, on average, 5.3 and 5.9 procedures, respectively. This difference was significant (P value = 0.01). Patients were also compared based on continuity of care. Patients who had their cleft surgeries by multiple plastic surgeons affiliated with our children's hospital had significantly more surgeries (P = 0.01). A surgical outlier subset of 17 patients (24%) was identified who had more than 10 surgeries. These patients also had, on average, 11.3 (unilateral cleft lip and palate) and 11.8 (bilateral cleft lip and palate) anesthesia events; this is in contrast to the nonoutliers who had, on average, 4.1 to 8 anesthesia events. This retrospective review identifies patient and clinical factors that contributed to the number of surgeries and anesthesia events that children with a cleft underwent from birth to adulthood at a single children's hospital. We found that "heralding" events, such as palatal fistula and multiple nasal or lip revisions, can put children at risk for an increasing--and perhaps deleterious--number of surgery and anesthesia events.


Self-organization of atoms along a nanophotonic waveguide.
Atoms coupled to nanophotonic interfaces represent an exciting frontier for the investigation of quantum light-matter interactions. While most work has considered the interaction between statically positioned atoms and light, here we demonstrate that a wealth of phenomena can arise from the self-consistent interaction between atomic internal states, optical scattering, and atomic forces. We consider in detail the case of atoms coupled to a one-dimensional nanophotonic waveguide and show that this interplay gives rise to the self-organization of atomic positions along the waveguide, which can be probed through distinct characteristics in the reflection and transmission spectra.


Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes.
Chronic inflammation in liver tissue is an underlying cause of hepatocellular carcinoma. High levels of inflammatory cytokine IL18 in the circulation of patients with hepatocellular carcinoma correlates with poor prognosis. However, conflicting results have been reported for IL18 in hepatocellular carcinoma development and progression. In this study, we used tissue specimens from hepatocellular carcinoma patients and clinically relevant mouse models of hepatocellular carcinoma to evaluate IL18 expression and function. In a mouse model of liver fibrosis that recapitulates a tumor-promoting microenvironment, global deletion of the IL18 receptor IL18R1 enhanced tumor growth and burden. Similarly, in a carcinogen-induced model of liver tumorigenesis, IL18R1 deletion increased tumor burden. Mechanistically, we found that IL18 exerted inflammation-dependent tumor-suppressive effects largely by promoting the differentiation, activity, and survival of tumor-infiltrating T cells. Finally, differences in the expression of IL18 in tumor tissue versus nontumor tissue were more predictive of patient outcome than overall tissue expression. Taken together, our findings resolve a long-standing contradiction regarding a tumor-suppressive role for IL18 in established hepatocellular carcinoma and provide a mechanistic explanation for the complex relationship between its expression pattern and hepatocellular carcinoma prognosis. Cancer Res; 76(8); 2394-405. ©2016 AACR.


Long-term performance evaluation of positron emission tomography: analysis and proposal of a maintenance protocol for long-term utilization.
Positron emission tomography (PET) scanners require periodic monitoring in order to maintain scanner performance. The aim of the present study was to examine the deterioration of PET scanner performance caused by aging. We retrospectively examined PET scanner performance alterations in terms of sensitivity, spatial resolution, false coincidences due to scatter and random coincidences based on 13 years of follow-up data, including data when the PET scanner underwent an overhaul at the 10th year after installation. Sensitivity and scatter fraction were calculated by using cross calibration factor (CCF) measurement data, which are collected routinely. Efficacy of the examining the sensitivity and scatter was confirmed by NEMA measurements. Trans-axial resolution was measured as full width at half-maximum (FWHM) and full width at tenth-maximum (FWTM) at 0-20 cm offset from the field of view (FOV) center at the time of installation, 8 years after installation, and immediately after the overhaul. Random coincidence rate fraction was measured in a wide range of count rates before and after the overhaul. The results indicated that the total reduction of sensitivity during the first 10 years was 41% of the initial value in terms of NEMA measurement, and that the annual reduction of sensitivity progressed at a rate of 4.7% per year in terms of CCF measurement data. The changes in sensitivity can be calculated using CCF measurement data. Regarding the spatial resolution, mean FWHM and FWTM values were increased by 1.7 and 3.6%, respectively, in 8 years after installation. The relative scatter fraction was significantly increased compared with that before the overhaul. The random fraction decreased by 10-15% after the overhaul within a certain range of random count rates (1-120 kcps). In the case of our scanner, the parameter that displayed the largest change was the sensitivity, and this change was thought to be caused by the reduction of photomultiplier tube (PMT) gain, although the changes in PMT gain can cause various types of performance deterioration, as investigated in this study. We observed that the sensitivity of our PET scanner generally deteriorated due to aging. Sensitivity monitoring using CCF measurements can be an easy and useful method for monitoring and maintaining the performance of PET scanners against aging. Since the data were obtained from a single scanner, the authors would encourage the initiation of a follow-up study involving various scanners.


The Long Non-Coding RNA ENST00000489676 Influences Papillary Thyroid Cancer Cell Proliferation and Invasion through Regulating MiR-922.
Purpose: Long noncoding RNAs (lncRNAs) have been reported to be associated with the growth and progression of numerous cancers. The aim of this study was to explore the potential function and molecular mechanism of lncRNA ENST00000489676 in the proliferation and invasion of papillary thyroid cancer (PTC). Methods: QRT-PCR (quantitative reverse transcriptase-polymerase chain reaction) was used to determine the levels of ENST00000489676. CCK-8 (Cell Counting Kit-8) assay and colony formation assay were performed to detect the cell proliferation. Flow cytometry was used to analyze the cell cycle. Transwell and scratch assay were performed to detect the migration and invasion ability. Results: The expression of ENST00000489676 was significantly overexpressed in TPC1 compared to KTC1 cell lines. When ENST00000489676 expression was knocked down, the proliferation, migration and invasion ability as well as cell cycle were all promoted in PTC cell lines, while those abilities were all suppressed when ENST00000489676 overexpressed. Overexpression of ENST00000489676 could inhibit cell proliferation, migration and invasion in vitro. Moreover, ENST00000489676 may mediate tumor suppression in PTC cells through suppressing miR-922. Conclusions: ENST00000489676 negatively regulated the proliferation, migration invasion and cell cycle of PTC. The overexpression of ENST00000489676 inhibited the progression of PTC through suppressing miR-922. ENST00000489676 could be act as a novel diagnosis marker and a potential therapeutic target for PTC.


Previous sphincter repair does not affect the outcome of repeat repair.
As many as 60 percent of patients present with recurrent symptoms of fecal incontinence after anterior overlapping anal sphincter repair. The aim of this study was to assess the outcome of repeat overlapping anal sphincter repair. All female patients with obstetric sphincter damage who underwent anterior overlapping sphincter repair between November 1988 and June 2000 were reviewed. All patients were preoperatively assessed by anorectal manometry, electromyography, and pudendal nerve terminal motor latency; manometry was repeated during follow-up. Preoperative endoanal ultrasonography was available only after 1990. Clinical outcome was assessed according to the Cleveland Clinic Florida Incontinence Score. One hundred fifty-one patients were available for analysis, 115 without previous surgery and 36 after at least one previous sphincter repair. The median follow-up was 13 (range, 1-64) months and 20 (range, 2-96) months, respectively. The median incontinence score improved from 18 to 5 (P < 0.0001) in patients without previous repair and from 17.5 to 7 (P < 0.0001) in patients after previous repair. In the former group, the outcome was good in 67 (58 percent) patients, adequate in 19 (16.5 percent), and poor in 29 (25.5 percent). In the group with previous sphincter repair, the outcome was good in 18 patients (50 percent), adequate in 4 (11 percent), and poor in 14 (39 percent; P = 0.2646). The mean resting pressure increased from 20 (range, 3-43) mmHg to 24 (range, 10-44) mmHg and from 27 (range, 4-56) mmHg to 32 (range, 16-45) mmHg, respectively. The mean squeeze pressure increased from 60 (range, 23-63) mmHg to 67 (range, 33-114) mmHg and from 54 (range, 25-90) mmHg to 70 (range, 34-95) mmHg, respectively. Previous sphincter repair does not affect clinical outcome. Repeat anterior overlapping sphincter repair yields a significant improvement in the continence score and should be considered as the treatment of choice in patients with fecal incontinence who have had previous sphincter repair and residual anterior sphincter damage.


Fairness of recommender systems in the recruitment domain: an analysis from technical and legal perspectives.
Recommender systems (RSs) have become an integral part of the hiring process, be it via job advertisement ranking systems (job recommenders) for the potential employee or candidate ranking systems (candidate recommenders) for the employer. As seen in other domains, RSs are prone to harmful biases, unfair algorithmic behavior, and even discrimination in a legal sense. Some cases, such as salary equity in regards to gender (gender pay gap), stereotypical job perceptions along gendered lines, or biases toward other subgroups sharing specific characteristics in candidate recommenders, can have profound ethical and legal implications. In this survey, we discuss the current state of fairness research considering the fairness definitions (e.g., demographic parity and equal opportunity) used in recruitment-related RSs (RRSs). We investigate from a technical perspective the approaches to improve fairness, like synthetic data generation, adversarial training, protected subgroup distributional constraints, and post-hoc re-ranking. Thereafter, from a legal perspective, we contrast the fairness definitions and the effects of the aforementioned approaches with existing EU and US law requirements for employment and occupation, and second, we ascertain whether and to what extent EU and US law permits such approaches to improve fairness. We finally discuss the advances that RSs have made in terms of fairness in the recruitment domain, compare them with those made in other domains, and outline existing open challenges.


Distraction Osteogenesis in Craniofacial Surgery: Past, Present, and Future.
Distraction osteogenesis (DO) is considered one of the treatments of choice for the surgical correction of malformations of the craniofacial skeleton. This is due to its ability to generate bone at the distraction site along with the accompanying soft tissue changes, the possibility to combine DO with traditional orthognathic procedures and the successful reported long-term outcomes following its application to various craniofacial deformities. The aim of this review is to present an overview of the literature on the evolution of DO applications in craniofacial surgery through the last 35 years.


Dispersion-free optical coherence depth sensing with a spatial frequency comb generated by an angular spectrum modulator.
As an alternative to the conventional optical frequency comb technique, a spatial frequency comb technique is proposed for dispersion-free optical coherence depth sensing. Instead of generating an optical frequency comb over a wide range of time spectrum, we generate a spatial frequency comb by modulating the incident angle of a monochromatic plane wave with a spatial light modulator (SLM). The use of monochromatic light combined with the SLM enables dispersion-free depth sensing that is free from mechanical moving components.


Small bowel lesions in patients with iron deficiency anaemia without overt bleeding: a multicentre study.
The diagnostic work-up in iron deficiency anaemia (IDA) patients can be challenging when bleedings or malabsorption are not clinically manifest. Lesions on the small bowel mucosa may cause IDA. We evaluated the prevalence of lesions on the small bowel mucosa detected at Videocapsule Endoscopy (VCE) in IDA patients following negative upper and lower endoscopies. Clinical and endoscopic data collected in 5 centres were retrieved. Lesions with a high bleeding potential (P2) were computed, and predictive factors investigated at multivariate analysis. By considering data of 230 patients, the endoscopic examination detected a total of 96 (41.7%; 95% CI: 35.4-48.1) P2 lesions on the small bowel mucosa, including 4 (1.7%) cancers. The use of non-steroidal anti-inflammatory drugs was found to be the only associated factor at both univariate (OR: 5.7, 95% CI: 2.4-13.4; P <0.001) and multivariate (OR: 2.8; 95% CI: 1.7-3.9, P <0.01) analyses. Present study showed that evaluation of small bowel mucosa with VCE allows to disclose a potential cause of IDA in near half patients. The cooperation between haematologists and gastroenterologists in the diagnostic work-up may be useful.


[Human lymph node asymmetry and its applied importance].
At studying various groups of the human lymph vessels (inguinal, axillary, peristernal, deep cervical, superior tracheobroncheal, etc.) a certain asymmetry in their structure has been noted. The number of similar lymph nodes at either side is not equal: their number is greater at the right side than at the left. As a rule, the range between maximum and minimum is greater in men than in women. Asymmetry of the male lymph nodes is more pronounced than that in the female. There are certain differences in size and position of the lymph nodes regarding large blood vessels. In most cases, the indices on number and size of the lymph vessels are inversely proportional. As to the microscopical structure of the lymph nodes, the asymmetry is revealed in different structure of only some structural components and separate cellular elements, which are assumed to be more labile at asymmetry of the human body functions. The data obtained on different structure of the left- and right-sided lymph nodes of the same name contribute to our knowledge on anatomy of these organs and can be used in practical medicine.


VA location and structural factors associated with on-site availability of reproductive health services.
With the increasing number of women Veterans enrolling in the Veterans Health Administration (VA), there is growing demand for reproductive health services. Little is known regarding the on-site availability of reproductive health services at VA and how this varies by site location and type. To describe the on-site availability of hormonal contraception, intrauterine device (IUD) placement, infertility evaluation or treatment, and prenatal care by site location and type; the characteristics of sites providing these services; and to determine whether, within this context, site location and type is associated with on-site availability of these reproductive health services. We used data from the 2007 Veterans Health Administration Survey of Women Veterans Health Programs and Practices, a national census of VA sites serving 300 or more women Veterans assessing practice structure and provision of care for women. Hierarchical models were used to test whether site location and type (metropolitan hospital-based clinic, non-metropolitan hospital-based clinic, metropolitan community-based outpatient clinic [CBOC]) were associated with availability of IUD placement and infertility evaluation/treatment. Non-metropolitan CBOCs were excluded from this analysis (n = 2). Of 193 sites, 182 (94 %) offered on-site hormonal contraception, 97 (50 %) offered on-site IUD placement, 57 (30 %) offered on-site infertility evaluation/treatment, and 11 (6 %) offered on-site prenatal care. After adjustment, compared with metropolitan hospital based-clinics, metropolitan CBOCs were less likely to offer on-site IUD placement (OR 0.33; 95 % CI 0.14, 0.74). Compared with metropolitan hospital-based clinics, metropolitan CBOCs offer fewer specialized reproductive health services on-site. Additional research is needed regarding delivery of specialized reproductive health care services for women Veterans in CBOCs and clinics in non-metropolitan areas.


Smart dual imprinted Origami 3D-ePAD for selective and simultaneous analysis of vanillylmandelic acid and 5-hydroxyindole-3-acetic acid carcinoid cancer biomarkers using graphene quantum dots coated with dual molecularly imprinted polymers.
Measuring the levels of the biomarkers vanillylmandelic acid (VMA) and 5-Hydroxyindole-3-acetic acid (5-HIAA) is a valuable tool for clinical diagnosis not only of neuroblastoma or carcinoid syndrome, but also of essential hypertension, depression, migraine, and Tourette's syndrome. Herein, we explore using graphene quantum dots (GQDs) coated with molecularly imprinted polymer (MIP) as novel dual-imprinted sensors for selective and simultaneous determination of VMA and 5-HIAA in urine and plasma samples. The dual-MIP was successfully coated on the GQDs core via co-polymerization of (3-aminopropyl) triethoxysilane (APTES) and tetraethyl orthosilicate (TEOS), acting as functional and cross-linking monomers, respectively. In addition, we successfully created the dual imprinted VMA and 5-HIAA shell on the GQDs' core via a one-pot synthesis. We fabricated a facile and ready-to-use Origami three-dimensional electrochemical paper-based analytical device (Origami 3D-ePAD) for simultaneous determination of VMA and 5-HIAA using a GQDs@dual-MIP modified graphene electrode (GQDs@dual-MIP/SPGE). The Origami 3D-ePAD was designed to form a voltammetric cell on a three-layer foldable sheet with several advantages. For example, they were quickly assembled and enhanced the device's physical durability with the hydrophobic backup sheet. The developed dual imprinted Origami 3D-ePAD leads to substantially enhanced sensitivity and selectivity to electrochemical signal amplification generated from increasing the electrode-specific surface area, electrocatalytic activity, and the large numbers of dual imprinted sites for VMA and 5-HIAA detection. The synthetic recognition sites are highly selective for 5-HIAA and VMA molecules with an imprinting factor of 8.46 and 7.10, respectively. Quantitative analysis relying on square wave voltammetry reveals excellent linear dynamic ranges of around 0.001-25 μM, with detection limits of 0.023 nM for 5-HIAA and 0.047 nM for VMA (3Sb, n = 3). The Origami 3D-ePAD provides high accuracy and precision (i.e., recovery values of 5-HIAA ranged from 82.98 to 98.40 %, and VMA ranged from 83.28 to 104.39 %), and RSD less than 4.37 %) in urine and plasma samples without any evidence of interference. Hence, it is well suited as a facile and ready-to-use disposable device for point-of-care testing. It is straightforward, cost-effective, reproducible, and stable. Furthermore, it allows for rapid analysis (analysis time ∼20s) useful in medical diagnosis and other relevant fields.


The determinants of neurological phenotypes during acute hypertensive crises - a preliminary study.
Background and Purpose: Acute blood pressure elevations lead to wide spectrum of neurologic manifestations, ranging from no overt neurologic symptoms to catastrophic events like ICH. Little is known regarding the determinants of this clinical variability. We determined clinical and imaging features of hypertensive crisis patients with normal neurological examination, ICH and posterior reversible encephalopathy syndrome (PRES).Methods: Cranial MRI was performed in patients with hypertensive urgency or emergency but normal neurological examination. Their clinical characteristics, and imaging features regarding cerebral small vessel disease were compared to ICH and PRES patients.Results: Hypertensive ICH patients (n = 58) were older, less likely to have hyperlipidemia, less commonly used calcium channel blockers, and had higher burden of chronic cSVD features in comparison to hypertensive crisis patients with normal neurological findings (n = 51). Multivariate analyses revealed cSVD burden score (p = 0.003) to be related with ICH, while higher admission blood pressure levels (p < 0.001), hyperlipidemia (p = 0.006) and calcium channel blocker usage (p = 0.005) were more common in patients with normal neurological examination. The PRES (n = 9) group was comprised of younger patients with recent history of hypertension and low burden of cSVD.Conclusions: Hypertensive surge is associated with ICH when cSVD burden is high, probably caused by microvascular dysfunction secondary to long-standing hypertension, while the episode causes no structural damage if this burden is less. Although our observations are exploratory, short term but severe hypertension manifests with PRES possibly due to the absence of adaptive changes.


Preparation and in vitro characterization of carrier erythrocytes for vaccine delivery.
Erythrocytes as the most readily available and abundant cells within the body, have been studied extensively for their potential application as drug delivery carriers. In this study, human erythrocytes have been loaded by bovine serum albumin (BSA) as a model antigen/protein using hypotonic preswelling method for targeted delivery of this antigen to antigen-presenting cells (APCs). A series of in vitro tests have been carried out to characterize the carrier cells in vitro, including loading parameters, BSA and hemoglobin release kinetics, hematological indices, particle size distribution, SEM analysis, osmotic and turbulence fragility, and osmotic competency. BSA was loaded in erythrocytes with a loaded amount of 1.98+/-0.009mg with antigen release from carrier cells showing a zero-order kinetic consistent to that of the cell lysis. The apparent cell sizes, measured using laser scattering, were not significantly different from normal erythrocytes, but the real sizes, measured using SEM, and surface topologies were quite different between loaded and unloaded cells. The BSA-loaded cells were remarkably more fragile and less deformable compared to the normal cells. Totally, BSA-loaded erythrocytes seem to be a promising delivery system for reticuloendothelial system (RES) targeting of the antigens.


About the new significance and the contingent meaning of biological material and data in biobanks.
Since the end of the 1990s, the practice of biobanking--performed in and by actors called biobanks--has become a key practice for the life sciences and the biotechnologies, though the practice of biobanking is far from being something entirely new. Its significance, however, is indeed new, in the sense that the biological material and associated data collected in, and manipulated by, well-organised and often highly specialised facilities is transformed into an (epistemic) object with biovalue. In other words, the practice of biobanking signifies not only the collection, manipulation, and distribution of biological material and associated data in an organised manner involving various actors that govern or use the services of a biobank. Rather, it produces biobanks as sites of co-production of data-driven scientific knowledge. My paper draws on case studies of the history and practices of Généthon DNA and Cell Bank, the Biobank of Picardie, and the Tumour Bank of the Saint-Louis Hospital in a comparative manner. It presents biobanking as both a contingent practice and of an open, experimental character and concludes that it is transforming into a data-driven practice pursued in an industrialized manner.


An evolutionarily conserved glycine-tyrosine motif forms a folding core in outer membrane proteins.
An intimate interaction between a pair of amino acids, a tyrosine and glycine on neighboring β-strands, has been previously reported to be important for the structural stability of autotransporters. Here, we show that the conservation of this interacting pair extends to nearly all major families of outer membrane β-barrel proteins, which are thought to have originated through duplication events involving an ancestral ββ hairpin. We analyzed the function of this motif using the prototypical outer membrane protein OmpX. Stopped-flow fluorescence shows that two folding processes occur in the millisecond time regime, the rates of which are reduced in the tyrosine mutant. Folding assays further demonstrate a reduction in the yield of folded protein for the mutant compared to the wild-type, as well as a reduction in thermal stability. Taken together, our data support the idea of an evolutionarily conserved 'folding core' that affects the folding, membrane insertion, and thermal stability of outer membrane protein β-barrels.


Lunarperiodic variation of the phase-angle difference in nocturnal animals under natural Zeitgeber-conditions near the equator.
Several months' studies under natural illumination conditions in the vicinity of the equator show that night monkeys (Aotus trivirgatus), and leaf-nosed bats (Artibeus lituratus) exhibit species-specific lunarperiodic changes of the phase position of their activity rhythm to the Zeitgeber rhythm (Figures 1-3). These changes are closely to nightly illumination conditions. In Aotus the phase-angle differences (p.a.ds) of the onset and end of the activity phase, and in Artibeus the p.a.ds of the midpoint and end of the activity phase are significantly dependent upon the phases of the moon. In the African fruit bat Rousettus aegyptiacus, and in the leaf-nosed bat Phyllostomus hastatus no statistically significant lunarperiodic changes of the p.a.ds could be detected. These results cannot be explained by means of current models concerning the mechanism of synchronisation of biological oscillation. They appear to be, instead, expressions of a periodic masking of the real phase-position due to direct effects of light intensity on the level of activity which which itself is determined by the circadian rhythm. Aschoff's rule, which states that the earlier a species or an individual awakes the later it terminates its daily phase of activity, is partly confirmed for the nocturnal mammals examined in the present study.


High feedback versus low feedback of prenatal ultrasound for reducing maternal anxiety and improving maternal health behaviour in pregnancy.
Prenatal ultrasound is one of many techniques used in screening and diagnosis. It gives parents instant access to the images of the fetus. Receiving information promotes knowledge and understanding, but it may also increase maternal anxiety. To compare high feedback versus low feedback during prenatal ultrasound for reducing maternal anxiety and improving maternal health behaviour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2010), the Central Register of Controlled Trials (The Cochrane Library 2010, Issue 1), MEDLINE (January 1966 to 1 March 2010), and the metaRegister of Controlled Trials (mRCT) (March 2010). We handsearched citation lists of relevant publications. We did not apply any language restrictions. Randomized controlled trials (RCTs) of high feedback (women can see the monitor screen and receive detailed visual and verbal explanations) versus low feedback (women can not see the monitor screen and women are given only a summary statement of the scan) during prenatal ultrasound. The primary outcome measure was maternal state anxiety. Two authors independently assessed trial quality and extracted data. We have expressed results as risk ratio (RR) or mean differences, together with their 95% confidence intervals (CI). We included four studies (365 women). Three RCTs(346 participants) reported the effect of high versus low feedback during ultrasound on state anxiety scores (mean difference 0.92, 95% CI -0.58 to 2.43). Two trials (148 participants) reported women's views of the level of feedback. They do not show that women in the high feedback groups are more likely to choose very positive adjectives to describe their feelings after the scan (RR 3.30; 95% CI 0.73 to 14.85). Women who had a high feedback during ultrasound were more likely to stop smoking during pregnancy (one trial, 129 participants; RR 2.93; 95% CI 1.25 to 6.86) and to avoid alcohol during pregnancy (one trial, 129 participants; RR 2.96; 95% CI 1.15 to 7.60). There is insufficient evidence to support either high or low feedback during a prenatal ultrasound to reduce maternal anxiety and promote health behaviour.


Subarachnoid haemorrhage associated with infectious endocarditis: case report and literature review.
Cases of subarachnoid haemorrhage (SAH) as a presenting feature or soon after initiation of antibiotics in infectious endocarditis (IE) have been reported. However, most had documented mycotic aneurysms as the source of haemorrhage. Reports of IE associated with SAH of unclear source are rare. A case of SAH associated with IE is reported. We also reviewed our data set on neurological complications of IE at Mayo Clinic Rochester from 1980 to 1996 for additional cases. In addition to the index case, we identified seven cases of SAH amongst 489 patients (1%) with IE for a total of eight cases. In six patients, initial cerebral angiography, magnetic resonance angiography or autopsy did not show aneurysm or other aetiology for the SAH. A mycotic aneurysm was noted in one case and the other patient had an unruptured mycotic aneurysm of the tip of basilar artery. SAH was located in the basal cistern in two patients, sylvian fissure in three, and hemispheric sulci in three. SAH is an uncommon complication of IE, and in the setting of IE a specific cause, such as mycotic aneurysm, may not be identified.


Endometriosis Presenting as Recurrent Haemorrhagic Ascites: A Case Report and Literature Review.
Endometriosis is a common condition that occurs in 6-10% of all reproductive age women. This number increases to approximately 40% in women with infertility and nearly 75% in women with complaints of chronic pelvic pain. Endometriosis is characterized by the presence of endometrial glands and stroma outside the uterine cavity. The most common complaints associated with endometriosis are dysmenorrhea and pelvic pain; however, patients often present with a variety of symptoms and on occasion are asymptomatic. When presenting with haemorrhagic ascites, endometriosis mimics ovarian malignancy. Conservative medical treatment is a feasible management option, especially in young patients who desire to preserve fertility. This article aims to present an extremely rare presentation of endometriosis, haemorrhagic ascites, and a review of the associated literature.


Immunoglobulin A anti-tissue transglutaminase antibody deposits in the small intestinal mucosa of children with no villous atrophy.
Anti-tissue transglutaminase (anti-TG2) immunoglobulin A (IgA) autoantibodies are detectable in the serum of most patients with untreated celiac disease (CD). Their deposits in the intestine of patients with CD with severe enteropathy are considered specific for this condition. The histological spectrum of CD includes cases with normal villous architecture. The aim of this study was to look for anti-TG2 IgA deposits in the intestine of children with normal villous architecture and to relate them with other markers of gluten sensitivity. A total of 57 children with normal duodenal villous architecture and markers of gluten sensitivity were considered. Of those, 39 showed positive serum anti-endomysium antibodies and/or high levels of anti-TG2 antibodies (group 1), and 18 were seronegative with only a greater density of gammadelta intraepithelial lymphocytes (group 2). Thirty-four children with no markers of gluten sensitivity and a normal mucosa represented the control group (group 3). The duodenal sections of all patients were investigated for deposited anti-TG2 IgA by double immunofluorescence. Human lymphocyte antigen molecular typing was performed. In group 1 and in group 2, 33 of 39 children (85%) and 12 of 18 children (66%) showed subepithelial anti-TG2 IgA intestinal deposits, respectively. Only in 3 of 34 (8.8%) children with no markers of gluten sensitivity were anti-TG2 IgA deposits noted. A subgroup of children with no serum CD-associated autoantibodies, but greater density of gammadelta intraepithelial lymphocytes, shows a clear anti-TG2 IgA deposition in the duodenal mucosa. These children must be investigated further for possible gluten sensitivity.


Assessment of the action spectrum for photooxidation in full fat bovine milk.
The action spectrum for photooxidation in full fat bovine milk was measured. Samples of milk with air or argon in headspace were exposed to narrow wavelength bands of light in the range 400-700 nm. Photooxidation in terms of off-flavors was measured by a sensory panel, volatile compounds by headspace solid phase micro extraction (SPME-GC-MS), and photobleaching of photosensitizers in milk (riboflavin, protoporphyrin IX and a chlorophyllic compound) by front face fluorescence spectroscopy. The action spectrum deviated significantly from the absorption spectrum of milk. Significant oxidation was induced by wavelengths around 400 nm and 500-650 nm in milk with air in headspace. Argon in headspace gave significant oxidation also at 700 nm. It is suggested that protoporphyrin IX and chlorophyll are responsible for oxidation induced by wavelengths >500 nm, and that also riboflavin is contributing from 400 to 500 nm.


An integrin αEβ7-dependent mechanism of IgA transcytosis requires direct plasma cell contact with intestinal epithelium.
Efficient IgA transcytosis is critical for the maintenance of a homeostatic microbiota. In the canonical model, locally-secreted dimeric (d)IgA reaches the polymeric immunoglobulin receptor (pIgR) on intestinal epithelium via simple diffusion. A role for integrin αE(CD103)β7 during transcytosis has not been described, nor its expression by intestinal B cell lineage cells. We found that αE-deficient (αE-/-) mice have a luminal IgA deficit, despite normal antibody-secreting cells (ASC) recruitment, local IgA production and increased pIgR expression. This deficit was not due to dendritic cell (DC)-derived retinoic acid (RA) nor class-switching defects, as stool from RAG-/- mice reconstituted with αE-/- B cells was also IgA deficient. Flow cytometric, ultrastructural and transcriptional profiling showed that αEβ7-expressing ASC represent an undescribed subset of terminally-differentiated intestinal plasma cells (PC) that establishes direct cell to cell contact with intestinal epithelium. We propose that IgA not only reaches pIgR through diffusion, but that αEβ7+ PC dock with E-cadherin-expressing intestinal epithelium to directly relay IgA for transcytosis into the intestinal lumen.


Clopidogrel and aspirin versus aspirin alone for the prevention of stroke in patients with a history of atrial fibrillation: subgroup analysis of the CHARISMA randomized trial.
Aspirin offers modest reduction in stroke in patients with atrial fibrillation. Whether combination of aspirin with clopidogrel offers additional protection is unclear. Post-hoc subgroup analysis of 593 participants with a history of atrial fibrillation in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) randomized trial testing clopidogrel 75 mg per day plus aspirin (75-162 mg per day) vs. aspirin alone in patients with stable cardiovascular disease or multiple cardiovascular risk factors. Mean patient age was 70 years, 78% were men, and hypertension, heart failure and diabetes were present in 78, 20 and 44%, respectively. During a median follow-up of 2.3 years, stroke (ischemic and hemorrhagic) occurred in 15 of 298 assigned to clopidogrel plus aspirin and in 14 of 285 given aspirin alone (hazard ratio, HR, 1.03, 95% CI 0.49-2.1). There was no difference in all-cause mortality (HR 1.1, 95% CI 0.6-1.9) or in the composite of stroke, myocardial infarction, or vascular death (HR = 1.2, 95% CI 0.7-2.0). Severe/fatal extracranial hemorrhage occurred in 6 patients with combination vs. 3 with aspirin alone. This post-hoc subgroup analysis does not support the use of this combination over aspirin alone in patients with a history of atrial fibrillation pending results of ongoing larger randomized trials.


It is easy to see, but it is better to foresee: a case report on the favourable alliance between CardioMEMS and levosimendan.
In the past years, different devices have been investigated to help in identifying early decompensation events in patients with heart failure (HF) and reduced ejection fraction (EF), reducing hospital admissions. In this report, we present the first patient experience with levosimendan infusion led by CardioMEMS. A 68-year-old man with HF and reduced EF with more than 20 hospitalizations for exacerbation of HF was enrolled in our HF Clinic from October 2017. Echocardiogram showed a dilated left ventricle with severely reduced EF (29%) and increased pulmonary artery systolic pressure (40 mmHg). From October 2017 to May 2019, the patient went through numerous hospitalizations, despite optimal medical therapy; subsequently, was adopted a strategy of levosimendan infusions guided by CardioMEMS. Levosimendan infusions improved haemodynamic and pressure profiles. The patient was monitored daily by CardioMEMS, and from June to December 2019, he had only two hospitalizations scheduled for levosimendan infusion and none for HF exacerbation. Our case supports the combination of CardioMEMS and levosimendan for the optimal management of patients with advanced HF. These results further strengthen the development of a randomized clinical trial to demonstrate the clinical usefulness of this device in combination with the levosimendan infusion programme in advanced HF patients.