Distinguishing and treating demoralization syndrome in cancer: A review.
Demoralization, characterized by a persistent inability to cope, as well as helplessness, hopelessness, and despair, is highly prevalent in oncology, with between 36% to 52% of patients exhibiting demoralization syndrome. Given established evidence linking demoralization in patients with cancer to physical symptom burden, quality of life, sleep disturbance, and suicidality, assessment and treatment of demoralization syndrome is critical for optimizing clinical and psychosocial outcomes. The term "demoralization" is highly relevant to the care of patients with cancer facing life-limiting illnesses. Indeed, demoralization can be conceptualized as a feeling state characterized by the perception of being unable to cope with some pressing problems and/or of lack of adequate support from others. Despite a considerable overlap in symptoms, demoralization and depression should be regarded as distinct and independent clinical syndromes. Patients who are demoralized but not clinically depressed often describe a sense of subjective incompetence and do not report anhedonia (i.e., loss of interest and inability to enjoy things). Although the definition of demoralization is now included as a distinct syndrome in the International Classification of Diseases (ICD)-11, it has been neglected by the current U.S. official nosology in psychiatry, such as the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR). As such, demoralization syndrome may be under- or misdiagnosed and treated ineffectively in the oncology setting, potentially prolonging suffering and influencing cancer outcomes. Optimization of methods to diagnose and assess demoralization syndrome is critical to underpin rigorous studies evaluating the efficacy of psychotherapeutic and pharmacological interventions for patients with cancer experiencing demoralization. Our review supports the use of specific diagnostic criteria for demoralization in cancer patients, introduces methodological considerations relevant to treatment studies, and presents a novel measurement approach to the assessment of demoralization severity with the Clinical Interview for Demoralization (CIDE).


Fast, Easy, and Good: Assessing Entrustable Professional Activities in Psychiatry Residents With a Mobile App.
Entrustable professional activities (EPAs) can be used to operationalize competency-based medical education. Mobile apps can efficiently capture feedback based on direct observation. To leverage the benefits of both, the authors developed an assessment tool that combines EPAs with mobile technology. The authors designed an app to collect EPA data based on direct observation using human-technology interface guidelines. Data collected in the app included: name of resident, the 13 end-of-training EPAs for psychiatry, entrustment ratings, and corrective narrative feedback. The app was implemented in an outpatient continuity clinic for second-year psychiatry residents over a 10-month period between September 2017 and June 2018. Ten faculty-resident dyads piloted the app. To assess the feasibility, utility, and validity of this intervention, the authors examined 3 outcomes: (1) utilization (mean time to complete each assessment; percentage of dyads who completed 10 assessments), (2) quality of the comments (proportion of comments that were behaviorally specific and actionable), and (3) correlation between entrustment level and resident experience (defined as days elapsed since the beginning of the experience). A total of 99 assessments were completed during the pilot. Mean time to complete an assessment was 76 seconds (standard deviation = 50 seconds, median = 67 seconds). Only 6 of the 10 dyads completed at least 10 assessments. Of all comments, 95% (94) were behaviorally specific and actionable and 91% (90) were corrective. Entrustment scores correlated moderately with resident experience (r = 0.43, P < .001). The authors' EPA mobile app was efficient, generated high-quality feedback, and produced entrustment scores that improved as the residents gained experience. Challenges included uneven adoption. Looking forward, the authors plan to examine the enablers and barriers to adoption from an implementation science perspective.


Removal of Cr(VI) from aqueous solution by two Lewatit-anion exchange resins.
The sorption of hexavalent chromium, Cr(VI), from aqueous solutions on macroporous resins containing tertiary amine groups (Lewatit MP 62 and Lewatit M 610) was studied at varying Cr(VI) concentrations, adsorbent dose, pH, contact time and temperatures. The concentration of chromium in aqueous solution was determined by inductively coupled plasma spectrometry (ICP-AES). Batch shaking sorption experiments were carried out to evaluate the performance of Lewatit MP 62 and Lewatit M 610 anion exchange resins in the removal of Cr(VI) from aqueous solutions. The ion-exchange process, which is pH dependent, shows maximum removal of Cr(VI) in the pH range 2-6 for an initial Cr(VI) concentration of 100 ppm. The sorption increases with the decrease in pH and slightly decreases with the increase in temperature. Both ion exchangers had high bonding constants with Lewatit M 610 showing stronger binding. It was observed that the maximum adsorption capacity of 0.40 mmol of Cr(VI)/g for Lewatit MP 62 and 0.41 mmol of Cr(VI)/g for Lewatit M 610 was achieved at pH of 5.0. The thermodynamic parameters (free energy change, DeltaG degrees ; enthalpy change, DeltaS degrees ; and entropy change, DeltaH degrees ) for the sorption have been evaluated. The rise in temperature caused a slight decrease in the value of the equilibrium constant (Kc) for the sorption of Cr(VI) ion. The sorption of Cr(VI) on the resin was rapid during the first 15 min and equilibrium was found to be attained within 30 min. The sorption of Cr(VI) onto the resins followed reversible first-order rate kinetics. Such ion exchange resins can be used for the efficient removal of chromium from water and wastewater.


Quantifying mental foramen position in extant hominoids and Australopithecus: implications for its use in studies of human evolution.
The location of the mental foramen on the mandibular corpus has figured prominently in debates concerning the taxonomy of fossil hominins and Gorilla gorilla. In this study we quantify the antero/posterior (A/P) position of the mental foramen across great apes, modern humans and Australopithecus. Contrary to most qualitative assessments, we find significant differences between some extant hominoid species in mental foramen A/P position supporting its potential usefulness as a character for taxonomic and phylogenetic analyses of fossil hominoids. Gorilla gorilla, particularly the eastern subspecies, with a comparatively longer dental arcade and fossil and extant hominins with reduced canines and incisors tend to exhibit more anteriorly positioned mental foramina. Conversely, Pan troglodytes exhibits more posteriorly positioned mental foramina. Variation in this character among Gorilla gorilla subspecies supports recent taxonomic assessments that separate eastern and western populations. In all taxa other than Pan troglodytes the A/P position of the mental foramen is positively allometric with respect to dental arcade length. Thus, within each of these species, specimens with longer dental arcades tend to have more posteriorly positioned mental foramina. Those species with greater sexual dimorphism in canine size and dental arcade length (i.e., Gorilla gorilla and Pongo pygmaeus) exhibit more extreme differences between smaller and larger individuals. Moreover, among great apes those individuals with greater anterior convergence of the dental arcade tend to exhibit more posteriorly positioned mental foramina. Dental arcade length, canine crown area and anterior convergence are all significantly associated with mental foramen A/P position, suggesting that these traits may influence taxonomic variation in the A/P position of the mental foramen.


[Validation of an ELISA for the measurement of human IgG against serogroup B Neisseria meningitidis protein].
An indirect ELISA test was optimised in which B meningoccocus outer membrane proteins included in the Cuban Vaccine known as VA-MENGOC-BC were used as capture antigents. Specific antibodies in serum samples from vaccinated individuals were detected using a human anti-IgG conjugate, i.e. alklayne phosphatase, thus the reaction developed with a specific substrate called p-nitrophenilphophate. Standard serum was obtained from a reference standard, the gage curve range was 625 to 20,000/mL. The control serum was selected from the most interesting areas for the samples, hence, assay characteristics were determined. Intra-assay, inter-assay and total inaccuracies were lower than 10% in the most linear area of the curve. Detectability was 700/mL. Recovery, paralelism and linearity studies showed an under 10% inaccuracy.


Pseudomonas keratitis. The role of an uncharacterized exoprotein, protease IV, in corneal virulence.
The role of exoproteins in the pathogenesis of Pseudomonas aeruginosa keratitis was investigated in three animal models by assessing the relationship between corneal virulence and the activities of exotoxin A, elastase, alkaline protease, and an uncharacterized protease, protease IV. The four Pseudomonal strains tested included a prototype strain (ATCC 27853) producing exotoxin A, elastase, and alkaline protease; a parent strain (PA103) producing only exotoxin A and protease IV; a mutant (PA103-29) producing only protease IV; and a mutant (PA103-AP1) producing exotoxin A and having only approximately 5% of the protease IV activity of its parent. Corneal virulence was evaluated in the mouse scratch, rabbit scratch, and rabbit intrastromal models in terms of clinical signs (slit lamp examination, slit lamp examination), and viable bacteria. Protease IV, the only protease produced by PA103 and PA103-29, was found to produce a unique band on zymograms (120 kDa) and to react distinctively with a synthetic substrate. Evidence for the role of protease IV in corneal virulence included two findings: PA103-29,which produced protease IV but not the other exoproteins, caused infections that were as severe as those caused by the prototype strain (ATCC 27853) in all three models (P>0.24); and PA103-AP1, the strain deficient in 95% of the parent protease IV activity, mediated infections characterized by slit lamp examination scores significantly lower than those of infections caused by the parent (PA103) or the prototype strain (ATCC 27853) in the rabbit and mouse scratch models (P<0.02). Protease IV was found to be a novel Pseudomonas protease contributing to corneal virulence in rabbits and mice when infections were initiated at the corneal surface. Furthermore, production of protease IV in low quantities was sufficient for virulence when the topical stages of keratitis were bypassed by an intrastromal injection of Pseudomonas.


Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases.
Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other cell death modes, plays a pivotal role in regulating tumorigenesis and offers a new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications and posttranslational modifications (PTMs) promote anticancer drug resistance, cancer progression, and metastasis. Accumulating studies indicate that epigenetic modifications can transcriptionally and translationally determine cancer cell vulnerability to ferroptosis and that ferroptosis functions as a driver in nervous system diseases (NSDs), cardiovascular diseases (CVDs), liver diseases, lung diseases, and kidney diseases. In this review, we first summarize the core molecular mechanisms of ferroptosis. Then, the roles of epigenetic processes, including histone PTMs, DNA methylation, and noncoding RNA regulation and PTMs, such as phosphorylation, ubiquitination, SUMOylation, acetylation, methylation, and ADP-ribosylation, are concisely discussed. The roles of epigenetic modifications and PTMs in ferroptosis regulation in the genesis of diseases, including cancers, NSD, CVDs, liver diseases, lung diseases, and kidney diseases, as well as the application of epigenetic and PTM modulators in the therapy of these diseases, are then discussed in detail. Elucidating the mechanisms of ferroptosis regulation mediated by epigenetic modifications and PTMs in cancer and other diseases will facilitate the development of promising combination therapeutic regimens containing epigenetic or PTM-targeting agents and ferroptosis inducers that can be used to overcome chemotherapeutic resistance in cancer and could be used to prevent other diseases. In addition, these mechanisms highlight potential therapeutic approaches to overcome chemoresistance in cancer or halt the genesis of other diseases.


[Value of urinary cytology findings in the diagnosis of acute renal graft rejection].
Acute rejection of allograft is one of the most serious complications of renal transplantation that requires fast and precise diagnostic approach. In this paper our experience in cytologic urinalysis as a diagnostic method of the acute renal allograft rejection was reviewed. The study group included 20 of 56 patients with transplanted kidneys who were assumed for the acute allograft rejection according to allograft dysfunction and/or urine cytology findings. Histological findings confirmed allograft rejection in 4 patients. Urine sediment obtained in cytocentrifuge was air-dried and stained with May-Grunwald-Giemsa. Acute allograft rejection was suspected if in 10 fields under high magnification 15 or more lymphocytes with renal tubular cells were found. Acute transplant rejection occurred in 32.1% patients. In 15 patients clinical findings of the acute renal allograft rejection corresponded with cytological and histological findings (in the cases in which it was performed). Three patients with clinical signs of the acute allograft rejection were without cytological confirmation, and in 2 patients cytological findings pointed to the acute rejection, but allograft dysfunction was of different etiology (acute tubular necrosis, cyclosporine nephrotoxicity). In patients with clinical, cytological and histological findings of the acute allograft rejection urine finding consisted of 58% lymphocytes, 34% neutrophilic leucocytes and 8% monocytes/macrophages on the average. The accuracy of cytologic urinalysis related to clinical and histological finding was 75%. Urine cytology as the reliable, noninvasive, fast and simple method is appropriate as the a first diagnostic line of renal allograft dysfunction, as well as for monitoring of the graft function.


[Chemical safety (IV)--legal basis for control].
This work reviews the legal regulations constituting the basis for control of chemical substances present in the working and natural environment as well as in food and utility products in Poland. It has been found that there are many regulations which comply with legislative needs. However, a lack of general regulation on the protection of human health and the environment against the noxious effects of chemicals is widely acknowledged. The unsatisfactory condition of human health and environment in Poland may be attributed to the fact that the existing standards are often disregarded. The authors are of the opinion that implementation of an organizational and legal system of chemical safety would be an important step towards improving the existing situation.


Rat models of reward deficits in psychiatric disorders.
Loss of interest in rewarding activities is a hallmark of many psychiatric disorders and may be relevant for neurodegenerative disorders and patients suffering from brain injury. There is increasing evidence that deficits in reward-related behaviour are more complex than previously described. The traditional view of anhedonia as 'the inability to experience pleasure' may be too limited to fully encompass the types of reward deficit observed in these patients. Developments in methods to measure different aspects of reward processing in humans and animals are starting to provide insights into the complexity of this behaviour. In this article we consider the rodent models which have traditionally been used to study reward deficits in psychiatric disorders and consider their limitations relative to clinical findings. We then discuss work where methods derived from human neuropsychological tests are providing insights into the complexity of reward-related behaviour. Specifically, we consider tasks which investigate different aspects of reward-related behaviour focusing on learning and memory as well as decision-making and consider what these may mean in terms of how we model reward deficits in rodents.


The DNA binding factor Hmg20b is a repressor of erythroid differentiation.
In erythroblasts, the CoREST repressor complex is recruited to target promoters by the transcription factor Gfi1b, leading to repression of genes mainly involved in erythroid differentiation. Hmg20b is a subunit of CoREST, but its role in erythropoiesis has not yet been established. To study the role of Hmg20b in erythropoiesis, we performed knockdown experiments in a differentiation-competent mouse fetal liver cell line, and in primary mouse fetal liver cells. The effects on globin gene expression were determined. We used microarrays to investigate global gene expression changes induced by Hmg20b knockdown. Functional analysis was carried out on Hrasls3, an Hmg20b target gene. We show that Hmg20b depletion induces spontaneous differentiation. To identify the target genes of Hmg20b, microarray analysis was performed on Hmg20b knockdown cells and controls. In line with its association to the CoREST complex, we found that 85% (527 out of 620) of the deregulated genes are up-regulated when Hmg20b levels are reduced. Among the few down-regulated genes was Gfi1b, a known repressor of erythroid differentiation. Among the consistently up-regulated targets were embryonic β-like globins and the phospholipase HRAS-like suppressor 3 (Hrasls3). We show that Hrasls3 expression is induced during erythroid differentiation and that knockdown of Hrasls3 inhibits terminal differentiation of proerythroblasts. We conclude that Hmg20b acts as an inhibitor of erythroid differentiation, through the down-regulation of genes involved in differentiation such as Hrasls3, and activation of repressors of differentiation such as Gfi1b. In addition, Hmg20b suppresses embryonic β-like globins.


HIV stigma experiences and stigmatisation before and after a HIV stigma-reduction community "hub" intervention.
This study sought to explore, describe and determine whether an HIV stigma-reduction community "hub" intervention would change the HIV stigma experiences of people living with HIV (PLWH) and the stigmatisation by the community in an urban area in South Africa. A convergent parallel mixed-method design with a single case pre-test post-test design and an interpretive description approach was utilised. The sample for this study included 62 PLWH recruited through accessibility sampling and 570 community members recruited through random voluntary sampling. A sub-sample of both groups, selected using purposive voluntary sampling, was utilised for the in-depth interviews about stigma experiences of PLWH, and for perceptions and attitudes of the community toward PLWH. Both quantitative and qualitative data showed that stigma is present. Although no statistically significant changes were found, small practically significant changes were demonstrated in the experiences of PLWH and in the perceptions and attitudes of the community. The extent of changes was much more obvious in the responses of the PLWH and the community during their post-intervention qualitative interviews than the changes found with the quantitative measures. This study thus concludes that the HIV stigma-reduction community hub intervention was successful in initiating the onset of changes in a community through the PLWH and people living close to PLWH (PLC) as community mobilisers active in the community hub to mobilise their own communities towards HIV stigma reduction through social change.


Beyond protein binding: recent advances in screening DNA-encoded libraries.
DNA-encoded library (DEL) screening has emerged as an important method for early stage drug and probe molecule discovery. The vast majority of screens using DELs have been relatively simple binding assays. The library is incubated with a target molecule, which is almost always a protein, and the DNAs that remain associated with the target after thorough washing are amplified and deep sequenced to reveal the chemical structures of the ligands they encode. Recently however, a number of different screening formats have been introduced that demand more than simple binding. These include a format that demands hits exhibit high selectivity for target vs. off-targets, a protocol to screen for enzyme inhibitors and another to identify organocatalysts in a DEL. These and other novel assay formats are reviewed in this article. We also consider some of the most significant remaining challenges in DEL assay development.


Polarization-sensitive spectral-domain optical coherence tomography using a single line scan camera.
Polarization-sensitive optical coherence tomography can be used to measure the birefringence of biological tissue such as the human retina. Previous measurements with a time-domain polarization-sensitive optical coherence tomography system revealed that the birefringence of the human retinal nerve fiber layer is not constant, but varies as a function of location around the optic nerve head. Here we present a spectral-domain polarization-sensitive optical coherence tomography system that uses a spectrometer configuration with a single line scan camera and a Wollaston prism in the detection arm. Since only one camera has to be synchronized with other components in the system, the design is simplified considerably. This system is 60 times faster than a time-domain polarization-sensitive optical coherence tomography system. Data was acquired using concentric circular scans around the optic nerve head of a young healthy volunteer and the acquisition time for 12 circular scans was reduced from 72 s to 1.2 s. The acquired data sets demonstrate variations in retinal thickness and double pass phase retardation per unit depth that were similar to data from the same volunteer taken with a time-domain polarization-sensitive system. The double pass phase retardation per unit depth of the retinal nerve fiber layer varied between 0.18 and 0.40 degrees/mum, equivalent to a birefringence of 2.2 * 10(-4) and 4.8 * 10(-4) respectively, measured at 840 nm.


Validation of the revised Addenbrooke's Cognitive Examination (ACE-R) for detecting mild cognitive impairment and dementia in a Japanese population.
Early detection of dementia will be important for implementation of disease-modifying treatments in the near future. We aimed to investigate the diagnostic validity and reliability of the Japanese version of the revised Addenbrooke's Cognitive Examination (ACE-R J) for identifying mild cognitive impairment (MCI) and dementia. We translated and adapted the original ACE-R for use with a Japanese population. Standard tests for evaluating cognitive decline and dementing disorders were applied. A total of 242 subjects (controls = 73, MCI = 39, dementia = 130) participated in this study. The optimal cut-off scores of ACE-R J for detecting MCI and dementia were 88/89 (sensitivity 0.87, specificity 0.92) and 82/83 (sensitivity 0.99, specificity 0.99) respectively. ACE-R J was superior to the Mini-Mental State Examination in the detection of MCI (area under the curve (AUC): 0.952 vs. 0.868), while the accuracy of the two instruments did not differ significantly in identifying dementia (AUC: 0.999 vs. 0.993). The inter-rater reliability (ICC = 0.999), test-retest reliability (ICC = 0.883), and internal consistency (Cronbach's α = 0.903) of ACE-R J were excellent. ACE-R J proved to be an accurate cognitive instrument for detecting MCI and mild dementia. Further neuropsychological evaluation is required for the differential diagnosis of dementia subtypes.


[Effectiveness of the management of spinal problems with UMLP-07].
The UMLP-07 system for multifactorial treatment of the spinal column allows for the performance of various therapeutic procedures including relaxation of muscular-ligamentous structures by correction of their anatomical configuration due to flowability of the large mass of glass balls. The balls radioactively heated to the work temperature exhibit high thermal capacity and deeply warm up spinal structures thereby activating metabolic repair processes. Hinge elements of head and leg supports allow for controlled traction of the spine by elimination of functional blocks. Moreover, the balls produce acupuncture-like effect on biologically active points at the back of the body. Courses of therapy for the treatment of degenerative and dystrophic changes in the spine based on the use of UMLP-07 help to alleviate pain, correct asymmetry of right and left leg loading, improve dorsolumbar muscle hypertone, increase mobility of the spinal column.


Perlecan deficiency causes muscle hypertrophy, a decrease in myostatin expression, and changes in muscle fiber composition.
Perlecan is a component of the basement membrane that surrounds skeletal muscle. The aim of the present study is to identify the role of perlecan in skeletal muscle hypertrophy and myostatin signaling, with and without mechanical stress, using a mouse model (Hspg2(-/-)-Tg) deficient in skeletal muscle perlecan. We found that myosin heavy chain (MHC) type IIb fibers in the tibialis anterior (TA) muscle of Hspg2(-/-)-Tg mice had a significantly increased fiber cross-sectional area (CSA) compared to control (WT-Tg) mice. Hspg2(-/-)-Tg mice also had an increased number of type IIx fibers in the TA muscle. Myostatin and its type I receptor (ALK4) expression was substantially decreased in the Hspg2(-/-)-Tg TA muscle. Myostatin-induced Smad activation was also reduced in a culture of myotubes from the Hspg2(-/-)-Tg muscle, suggesting that myostatin expression and its signaling were decreased in the Hspg2(-/-)-Tg muscle. To examine the effects of mechanical overload or unload on fast and slow muscles in Hspg2(-/-)-Tg mice, we performed tenotomy of the plantaris (fast) muscle and the soleus (slow) muscle. Mechanical overload on the plantaris muscle of Hspg2(-/-)-Tg mice significantly increased wet weights compared to those of control mice, and unloaded plantaris muscles of Hspg2(-/-)-Tg mice caused less decrease in wet weights compared to those of control mice. The decrease in myostatin expression was significantly profound in the overloaded plantaris muscle of Hspg2(-/-)-Tg mice, compared with that of control mice. In contrast, overloading the soleus muscle caused no changes in either type of muscle. These results suggest that perlecan is critical for maintaining fast muscle mass and fiber composition, and for regulating myostatin signaling.


Clinical challenges facing patient participation in cardiac rehabilitation: cigarette smoking.
Cardiac rehabilitation (CR) is highly effective at reducing morbidity and mortality. However, CR is underutilized, and adherence remains challenging. In no group is CR attendance more challenging than among patients who smoke. Despite being more likely to be referred to CR, they are less likely to enroll, and much more likely to drop out. CR programs generally do not optimally engage and treat those who smoke, but this population is critical to engage given the high-risk nature of continued smoking in those with cardiovascular disease. This review covers four areas relating to CR in those who smoke. First, we review the evidence of the association between smoking and lack of participation in CR. Second, we examine how smoking has historically been identified in this population and propose objective screening measures for all patients. Third, we discuss the optimal treatment of smoking within CR. Fourth, we review select populations within those who smoke (those with lower-socioeconomic status, females) that require additional research and attention. Smoking poses a challenge on multiple fronts, being a significant predictor of future morbidity and mortality, as well as being strongly associated with not completing the secondary prevention program (CR) that could benefit those who smoke the most.


Galactose receptors and presentation of HIV envelope glycoprotein to specific human T cells.
Recognition of viral Ag and of the envelope glycoprotein of HIV (gp120) in particular by human Th cells is critical in the immune response to the viral Ag which includes antibody production and generation of cytotoxic cells. Procedures to increase antigenicity of gp120 are highly desirable in a vaccine perspective. Therefore, to induce activation of gp120-specific T cells by a liminal dose of Ag we enhanced uptake of gp120 by exploiting the galactose receptors on APC. Terminal sialic acid residues were removed by neuraminidase treatment from the carbohydrate side chains of the heavily glycosylated gp120. Galactose residues were exposed and hence recognized by galactose receptors on APC. The experiments demonstrated that 1) human monocytes and dendritic cells, but not cells of the B lineage, bear galactose receptor; 2) galactose receptors are indeed involved because enhanced presentation is inhibited by galactose and acetylgalactosamine and competed for by other asialoglycoproteins; 3) galactose receptors mediate internalization of Ag in intracellular compartments that intersect the processing and presenting pathways, resulting in activation of specific T cells; 4) antigenicity of gp120 for specific T cells can be enhanced by the exposure of galactose residues.


[Prevalence and risk factors of the lower back syndrome in automobile drivers].
To study epidemiology of low spine pain syndrome (LSPS) in drivers of municipal transport; to specify factors stimulating its onset. 600 drivers from Orenburg were screened for LSPS. Risk factors were evaluated in two groups of patients: 130 drivers with LSPS and 130 matched controls free of LSPS. The data obtained were entered to a standard questionnaire, risk factors were considered according to working place attestation. Low spine pain complaints were registered in each 1-2 drivers of three. Those having the pain were as a rule 30-50-year-olds with service duration more than 10 years. They had pain for more than 5 years. 94.6% of them had acute pain. Spinal function was restricted in most of the examined LSPS drivers. Major risk factors of LSPS were the following: toxic substances, static loads, physical overstrain, draughts. A relationship was found between intensive smoking, alcohol abuse, low physical activity and LSPS onset. High prevalence of LSPS, frequent exacerbations, impaired spinal function cause a high disability rate. Thus, LSPS is an important medicosocial problem.


Beta activity: a carrier for visual attention.
The alpha (8-13 Hz), beta (15-25 Hz) and gamma (30-60 Hz) bands of the EEG have been long studied clinically because of their putative functional importance. Old experimental results indicate that repetitive stimulation of the visual pathway evokes synchronous responses at the cortical level with a gain that depends on frequency; oscillations within relevant bands are less damped at subsequent processing levels than others. Our current results show in the cat that cortico-geniculate feedback has a build-in potentiation mechanism that operates at around the beta frequency and activates thalamic cells thus lowering the threshold for visual information transmission. We have also shown that enhanced beta activity is propagated along this feedback pathway solely during attentive visual behavior. This activity consists of 300-1,000 ms bursts that correlate in time with gamma oscillatory events. Beta-bursting activity spreads to all investigated visual centers, including the lateral posterior and pulvinar complex and higher cortical areas. Other supporting data are discussed that are concerned with the enhanced beta activity during attentive-like behavior of various species, including humans. Finally, we put forward a general hypothesis which attributes the appearance of oscillations within the alpha, beta and gamma bands to different activation states of the visual system. According to this hypothesis, alpha activity characterizes idle arousal of the system, while beta bursts shift the system to an attention state that consequently allows for gamma synchronization and perception.


Serum IGF-binding protein-6 and prostate specific antigen in breast cancer.
Recent studies have demonstrated the presence of the IGF-binding proteins (IGFBPs) and prostate specific antigen (PSA), an IGFBP protease. in human breast tissue. We sought to investigate the differences in serum IGFs, IGFBP-1, -3 and -6, and PSA between patients with surgically proven breast cancer and patients with benign breast disease. Concentrations of IGFs, IGFBP-1, -3 and -6, and PSA were determined in the sera from 57 patients with breast cancer (CA), and 46 women with benign breast disease (BBD) using immunoassays for IGFs and IGFBPs and an ultrasensitive ELISA for PSA. The mean (+/- S.E.M.) serum IGFBP-6 level in the CA group, 127 (16) ng/ml, was statistically significantly lower than in the BBD group, 157 (10) ng/ml (P = 0.016). Patients with CA had an elevated geometric mean serum PSA level of 0.018 (range: 0.0015-0.107) ng/ml, compared with 0.007 (range: 0.0015-0.019) ng/ml in women with BBD (P = 0.025). Mean serum IGFBP-1 concentrations were significantly lower in the CA group, 16 (2) ng/ml, versus 37 (4) ng/ml in the BBD group (P = 0.001). Mean serum IGFBP-3 concentrations were also lower in the CA group versus the BBD group, at 1981 (65) ng/ml, versus 2603 (140) ng/ml (P = 0.002) respectively. In the CA group, statistically significant correlations between PSA and IGFBP-6 (r = 0.413; P = 0.001), and between PSA and IGFBP-1 (r = -0.329; P = 0.021) were seen. Differences in IGF-I and -II between the two groups were not statistically significant. Lower serum concentrations of IGFBP-6, -3 and -1, but higher PSA concentrations were seen in the breast cancer group, and collectively these would suggest that there is an increase in bioavailable IGF-I in breast cancer.


Girls with fragile X syndrome: physical and neurocognitive status and outcome.
The fragile X syndrome, a common X-linked form of mental retardation and autism, affects females as well as males. Previous work has shown that approximately 35% of heterozygotes (women who carry the fragile X gene) demonstrate cognitive impairment. Thirty-two girls, 18 years or younger, who demonstrate the fragile X chromosome were evaluated and compared with 19 sisters who do not demonstrate the fragile X chromosome. Evaluations included a physical examination, behavioral assessment, and intelligence testing. Significant differences (in intellectual, behavioral, and physical features) were seen between the two groups. Twenty-five percent of fragile X-positive girls had an IQ in the mentally retarded range (IQ less than 70) and 28% had an IQ in the borderline range (70 to 84). Prominent ears, shyness, and poor eye contact were significant findings in fragile X-positive girls compared with fragile X-negative girls. Thirty-one percent of the fragile X-positive girls had significant attentional difficulties and most of these girls were successfully treated with stimulant medication. The majority of fragile X-positive girls in this study demonstrated significant behavioral and developmental problems which required identification and appropriate treatment. Pediatricians and health care providers should be aware of the frequency and manner with which fragile X affects females in order to initiate cytogenetic studies and treatment when indicated.


[The P-wave in systemic arterial hypertension].
An abnormal electrocardiographic P wave (AEPW) has been interpreted as indicative of heart failure, hypertrophy or dilatation of left atrium, or diminished left ventricular compliance. In order to determine the significance of this electrocardiographic sign we studied 47 cases of systemic arterial hypertension (SAH) without heart failure or coronary obstruction. Patients were assigned at 2 groups: group A (22 cases with P wave duration greater than 0.11 seg. (LEAD D2); and group B 25 cases with P wave duration less than this. The following data were studied in all cases: left ventricular ejection fraction (LVEF), left ventricular presystolic filling fraction (LVPFF), Sokoloff electrocardiographic index (SEI), final diastolic pressure of LV (FDPLV), and systolic arterial pressure (SAP). Results were: (Table: see text). There were not statistical differences in these values between groups A and B (including the FDPLV value not shown in the table). Correlation coefficient between duration of P wave and the other parameters studied were also no significant. AEPW in SAH is not related to an specifically degree of left ventricular hypertrophy or disfunction; therefore, hypertensive heart disease should not be classified taking in account this electrocardiographic sign.


All-trans retinoic acid inhibits proliferation of intestinal epithelial cells by inhibiting expression of the gene encoding Kruppel-like factor 5.
Retinoids are known inhibitors of epithelial cell proliferation. Previous studies indicate that Kruppel-like factor 5 (KLF5) is a pro-proliferative transcription factor. Here, we examined the effect of all-trans retinoid acid (ATRA) on proliferation of the intestinal epithelial cell line, IEC6. Treatment of IEC6 cells with ATRA inhibited their proliferation due to G1 cell cycle arrest. This inhibition was correlated with a decrease in the levels of KLF5 mRNA and promoter activity. In contrast, constitutive expression of KLF5 in stably transfected IEC6 cells with a KLF5-expressing plasmid driven by a viral promoter abrogated the growth inhibitory effect of ATRA. Moreover, ATRA inhibited proliferation of several human colon cancer cell lines with high levels of KLF5 expression but not those with low levels of KLF5 expression. Our results indicate that KLF5 is a potential mediator for the inhibitory effect of ATRA on intestinal epithelial cell proliferation.


[Effect of stress-inducing factors on the behavior of monkeys. I. The behavior of monkeys under acute emotional stress].
The behavior of Papio hamadryas pubertal males under the immobilizational stress conditions has been studied. It has been established that this very type of stress appeared to be a powerful irritant for the individuals of this species and age leading them into the depression state. The process of normalization of behavior after the 2-hour immobilization lasted for about 72 h. The main consequences of the stress were the violation of locomotion, the reception by individuals of unnatural postures, the trembling of limbs and the violation of coordination. The reaction of stress was greatly influenced by the position of individual in the hierarchic system. The dominant (alpha) and the most subdominant (z) males bore the stress easier. The intensification of food activity was marked within the male z. In certain period after the immobilization the tendency of the growth of friendly contacts between the individuals was found. The frequency of aggressive behavior after the stress lowered. The violation of manipulation activity was also marked. These regularities are of great importance for the reconstruction of group social behavior models of protohominid's societies.


The influence of HIV-1 exposure and infection on levels of passively acquired antibodies to measles virus in Zambian infants.
The age at which passively acquired antibodies are lost is critical to determining the optimal age for measles vaccination. Little is known about the influence of human immunodeficiency virus type 1 (HIV-1) infection on levels of prevaccination antibodies to measles virus. Antibodies to measles virus were measured by plaque reduction neutralization assay in HIV-1-infected, HIV-seropositive but uninfected, and HIV-seronegative Zambian infants aged 6 weeks to 9 months. Regression models were used to estimate age-specific antibody concentrations. Neutralizing antibodies to measles virus were measured in 652 plasma samples collected from 448 infants, of whom 61 (13.6%) were HIV-1 infected, 239 (53.4%) were HIV seropositive but uninfected, and 148 (33%) were HIV seronegative. The best fitting model suggests that HIV-1-infected infants have lower levels of passively acquired antibodies to measles virus at birth than do HIV-seronegative infants, but their antibody levels decrease more slowly. By 6 months of age, 91% (95% confidence interval, 83%-99%) of HIV-1-infected infants, 83% (95% confidence interval, 77%-89%) of HIV-seropositive but uninfected infants, and 58% (95% confidence interval, 51%-64%) of HIV-seronegative infants were estimated to have antibody levels that were unlikely to affect immune responses to measles vaccine (cutoff value for immune response, <50 mIU/mL). By 9 months of age, 99% of all infants had antibody levels <50 mIU/mL. Infants born to HIV-1-infected women are less likely to have passively acquired antibodies that would neutralize measles vaccine virus and, thus, have an increased risk of measles prior to the age of routine vaccination. Protection could be achieved by administration of the first dose of measles vaccine prior to 9 months of age.


MRI-based evaluation of multiorgan iron overload is a predictor of adverse outcomes in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.
The medical records of 44 pediatric patients who underwent allogeneic transplantation from 2011 to 2015 were retrospectively reviewed. Magnetic resonance imaging was used to measure iron concentrations in the liver, spleen, pancreas and bone. These patients were divided into two groups, 18 with non-elevated (< 100 μmol/g; Group 1) liver iron concentration before transplantation and 26 with elevated (> 100 μmol/g; Group 2) concentration . We compared transplant-related outcomes in the two groups. Iron overload was a negative prognostic risk factor for sinusoidal obstruction syndrome (OR = 17), osteoporosis (OR = 6.8), pancreatic insufficiency (OR = 17) and metabolic syndrome (OR = 15.1). No statistically significant differences in overall survival, disease-free survival, relapse incidence and incidence of acute or chronic graft-versus host disease were observed between the two groups. Mean times to engraftment of platelets (43.0 ± 35.3 days vs. 22.1 ± 9.5 days, p < 0.05) and neutrophils (23.1 ± 10.4 days vs. 17.8 ± 4.6 days, p < 0.05) appear significantly longer in Group 2 than in Group 1. Time to platelet engraftment showed statistically significant correlation with pre-transplant liver (r = 0.5775; p < 0.001) and bone iron concentration (r = 0.7305; p < 0.001). Post-transplant evaluation pointed out that iron concentration analyzed at the first follow-up peaked in all tissues. The iron accumulation was highest in bone, followed by the spleen, liver and pancreas. One year post transplant 9 of 18 (50%) patients in Group 1 and 6 of 22 (27%) in Group 2 presented with bone and/or spleen iron overload, but not with liver overload. Liver iron concentration is not always a reliable indicator of systemic siderosis or of the efficacy of chelation therapy.


Rubrerythrin from Clostridium perfringens: cloning of the gene, purification of the protein, and characterization of its superoxide dismutase function.
The food-borne pathogen Clostridium perfringens, which is an obligate anaerobe, showed growth under conditions of oxidative stress. In protein extracts we looked for superoxide dismutase (SOD) activities which might scavenge highly toxic superoxide radicals evolving under such stress conditions. Using the classical assay to detect SOD activity on gels after electrophoresis of C. perfringens proteins, we obtained a pattern of three major bands indicating SOD activity. The protein representing the brightest band was purified by three chromatographic steps. On the basis of 20 amino acids determined from the N terminus of the protein, we designed a degenerate oligonucleotide probe to isolate the corresponding gene. We finally sequenced an open reading frame of 195 amino acids (molecular mass, 21,159 Da) with a strong homology to the Desulfovibrio vulgaris rubrerythrin; therefore, we assumed to have cloned a rubrerythrin gene from C. perfringens, and we named it rbr. The C-terminal region of the newly detected rubrerythrin from C. perfringens contains a characteristic non-heme, non-sulfur iron-binding site -Cys-X-X-Cys-(X)12-Cys-X-X-Cys- similar to that found in rubrerythrin from D. vulgaris. In addition, three -Glu-X-X-His- sequences could represent diiron binding domains. We observed SOD activity in extracts of Escherichia coli strains containing the recombinant rbr gene from C. perfringens. A biological function of rubrerythrin as SOD was confirmed with the functional complementation by the rbr gene of an E. coli mutant strain lacking SOD activity. We therefore suppose that rubrerythrin plays a role as a scavenger of oxygen radicals.


The emergency department experience with prehospital ketamine: a case series of 13 patients.
There are no published reports examining the effects that ketamine administered prior to hospital arrival has on patients after their transfer to the emergency department (ED). In order to better understand the risk-benefit ratio for the prehospital use of ketamine, we examined the ED courses of 13 patients to whom emergency medical services (EMS) had administered ketamine for chemical restraint. This project was undertaken as part of our EMS system's continuous quality improvement (CQI) process. Data were collected retrospectively. All patients who were given ketamine by EMS providers under our medical direction were identified by prehospital care report queries. The treating paramedic and emergency physician were provided a CQI form after disposition of the patient from their care. The data were tabulated and descriptive statistics were calculated. Thirteen patients were given ketamine by EMS providers, with 13 of 13 having EMS records and 12 of 13 having ED records available for review. Time from ketamine administration to peak sedation was <5 minutes in 11 patients and 20 minutes for two patients. On emergency physician examination, five of 12 patients had Richmond Agitation Sedation Scale (RASS) scores of -5 (unarousable), one of 12 had a RASS score of -4 (deep sedation), four of 12 had RASS scores of -3 (moderate sedation), and two of 12 had RASS scores of -2 (light sedation). Three patients developed hypoxia, two in the ED and one prior to hospital arrival. Two of these patients required intubation and one was treated with jaw thrust. Indications for intubation were recurrent laryngospasm and intracranial bleeding. One additional patient experienced a single episode of hypersalivation, which was successfully treated with suctioning of the oropharynx. Of the nonintubated patients, three of 10 were diagnosed with an emergence reaction and five of 10 required additional sedation. The primary diagnosis on ED disposition was drug/ethanol intoxication (3), psychosis (4), intracranial bleeding (1), seizure (1), suicidal ideation (1), agitation (1), and altered mental status (1). Five patients were discharged from the ED, seven were admitted (two to the intensive care unit, four to medicine, and one to psychiatry), and one patient's disposition was unknown. In this series of 13 patients, ketamine administered by EMS produced moderate or deeper sedation. Respiratory complications included hypoxia, laryngospasm, and hypersalivation. Emergence reactions occurred in 30% of nonintubated patients, but they were successfully treated with small doses of benzodiazepines.


Novel effector control through modulation of a preexisting binding site of the aromatic-responsive sigma(54)-dependent regulator DmpR.
The Pseudomonas derived sigma(54)-dependent DmpR activator regulates transcription of the (methyl)phenol catabolic dmp-operon. DmpR is constitutively expressed, but its transcriptional promoting activity is positively controlled in direct response to the presence of multiple aromatic effectors. Previous work has led to a model in which effector binding by the amino-terminal region of the protein relieves repression of an intrinsic ATPase activity essential for its transcriptional promoting property. Here, we address whether the observed differences in the potencies of the multiple effectors (i) reside at the level of different aromatic binding sites, or (ii) are mediated through differential binding affinities; furthermore, we address whether binding of distinct aromatic effectors has different functional consequences for DmpR activity. These questions were addressed by comparing wild type and an effector specificity mutant of DmpR with respect to effector binding characteristics and the ability of aromatics to elicit ATPase activity and transcription. The results demonstrate that six test aromatics all share a common binding site on DmpR and that binding affinities determine the concentration at which DmpR responds to the presence of the effector, but not the magnitude of the responses. Interestingly, this analysis reveals that the novel abilities of the effector specificity mutant are not primarily due to acquisition of new binding abilities, but rather, they reside in being able to productively couple ATPase activity to transcriptional activation. The mechanistic implications of these findings in terms of aromatic control of DmpR activity are discussed.


Immunotherapy for glioma: from illusion to realistic prospects?
There is now evidence that the rules established for tumor immunology and immunotherapy in general are relevant for brain tumors. Treatment strategies explored have mainly involved vaccines using either tumor cells or components, and vaccines with defined synthetic peptides. This latter approach offers the advantage to select well-characterized antigens with selective or preferential expression on glioma. This is a prerequisite because collateral damage to the brain is not allowed. A second strategy which is reaching clinical trials is T cell therapy using the patients' own lymphocytes engineered to become tumor reactive. Tumor specificity can be conferred by forced expression of either a high-avidity T cell receptor or an antitumor antibody (the latter cells are called chimeric antigen receptors). An advantage of T cell engineering is the possibility to modify the cells to augment cellular activation, in vivo persistence and resistance to the tumor immunosuppressive milieu. A direct targeting of the hostile glioma microenvironment will additionally be required for achieving potent immunotherapy and various trials are assessing this issue. Finally, combining immunotherapy with immune checkpoint inhibitors and chemotherapy must be explored within rigorous clinical trials that favor constant interactions between the bench and bedside. Regarding immunotherapy for glioma patients, what was an unrealistic dream a decade ago is today a credible prospect.


Methylene blue phosphoramidite for DNA labelling.
We report the first synthesis of a methylene blue (MB) phosphoramidite derivative suitable for DNA solid-phase synthesis. The electrochemical and optical properties of the resulting MB modified oligonucleotides were confirmed. This new molecule is an important breakthrough in the design of new probes labelled with MB.


Proapoptotic and growth-inhibitory role of angiotensin II type 2 receptor in vascular smooth muscle cells of spontaneously hypertensive rats in vivo.
Angiotensin type 2 (AT(2)) receptors for angiotensin II suppress cell growth and induce apoptosis in vitro, but their role is poorly defined in vivo. We reported that transient induction of smooth muscle cell (SMC) apoptosis precedes DNA synthesis inhibition and aortic hypertrophy regression in spontaneously hypertensive rats treated with the AT(1) antagonist losartan or the converting-enzyme inhibitor enalapril. Although both drugs are equipotent in reducing SMC number, apoptosis occurs significantly earlier with losartan than enalapril. To examine the role of AT(2) receptors in this model, spontaneously hypertensive rats were given valsartan, an AT(1) antagonist, or enalapril, in combination or not with the AT(2) antagonist PD123319 for 1 or 2 weeks. Control rats received vehicle. Systolic blood pressure was reduced similarly by valsartan and enalapril but it was not significantly affected by PD123319. Angiotensin II plasma levels were increased (6-fold) with valsartan and reduced (80%) with enalapril but unaffected by PD123319. Valsartan significantly increased internucleosomal DNA fragmentation indicative of apoptosis at 1 week only (2.7-fold) and significantly reduced aortic mass (18%), SMC number (33%), and DNA synthesis (24%, measured by (3)H-thymidine incorporation) at 2 weeks. These valsartan-induced changes were prevented by PD123319. In contrast, enalapril-induced DNA fragmentation (2-fold increase at 2 weeks) was not affected by PD123319. PD123319 given alone did not affect growth or apoptosis. AT(1) and AT(2) receptor mRNAs were detected in the aorta by reverse transcription-polymerase chain reaction. Together, these results provide the first evidence that AT(2) receptors mediate vascular mass regression by stimulating SMC apoptosis in vivo, an effect seen during AT(1) receptor blockade but not during converting-enzyme inhibition.


Job Satisfaction among Occupational Therapy Practitioners: A Systematic Review of Quantitative Studies.
A comprehensive description of the factors associated with job satisfaction among occupational therapy practitioners is needed to promote their work well-being. This systematic review aimed to describe occupational therapy practitioners' job satisfaction and the related intra-, inter-, and extra-personal factors. Original peer-reviewed studies published between 2010 and 2019 were retrieved from four databases with the review including fourteen studies. The review was conducted according to the Joanna Briggs Institute guideline. The data were analyzed by narrative synthesis. Occupational therapy practitioners experienced high job satisfaction. Job satisfaction was found to be associated with significantly lower rates of turnover intention and higher rates of rewards. The relationships between job satisfaction, professional identity, exhaustion, and social environment showed conflicting results.


Overcoming the civil wars: the role of attachment styles between the impact of war and psychological symptoms and post-traumatic growth among Libyan citizens.
Background: Civil wars in Libya have impacted the mental health of the general population. The ways in which individuals cope with traumatic events are influenced by several psychological variables.Objectives: The present study aimed to investigate how post-traumatic stress symptoms (PTSS) are associated with psychological symptoms and post-traumatic growth (PTG), and to evaluate the role of avoidant and anxious attachment dimensions as mediators in these associations, among Libyan citizens.Method: Three-hundred participants (147 females; age 31.0 ± 8.4 years) completed the Impact of Event Scale - Revised, Experiences in Close Relationships, Patient Health Questionnaire, and Post-traumatic Growth Inventory - Short Form.Results: The structural equation model revealed that insecure attachment dimensions mediated the association between PTSS and psychological symptoms and PTG. PTSS were positively associated with psychological symptoms, PTG, and both insecure attachment dimensions. Insecure attachment dimensions were positively associated with psychological symptoms and negatively with PTG.Conclusion: The present findings contribute to growing empirical research on the roles of insecure attachment dimensions in the association between the impact of war, psychological symptoms, and PTG.


Premedication with Diclofenac and Precurarization with Atracurium on Succinylcholine-Induced Myalgia in Laparoscopic Cholecystectomy: A Double-Blinded Randomized Study.
Succinylcholine is the only available depolarizing neuromuscular blocker that has been widely used in the induction of anesthesia, and it is the drug of choice for rapid-sequence induction of anesthesia due to its rapid onset of effect and ultrashort duration of action owing to its rapid hydrolysis by acetyl-cholinesterase. Postoperative muscle pain (myalgia) and muscle stiffness are the most common side effects and are observed most frequently on the 1st postoperative day in ambulatory surgery. The use of succinylcholine in the induction of anesthesia and intubation in routine cases has been discouraged because of such adverse effects. However, because of its cost-effectiveness and easy availability, it is still used by some institutions routinely. This study aimed to study the efficacy of preoperative diclofenac along with atracurium precurarization in alleviating succinylcholine-induced myalgia. It is a double-blind randomized comparative study carried out in a tertiary care hospital. The study sample was 60 and divided into two equal groups. All data entered in MS-Excel Sheet and Wilcoxon signed-rank test were done for nonparametric data and one-way ANOVA for the parametric data. The normal distribution of the study sample was tested by the Shapiro - Wilk test. The fasciculations in the test group were much less than in the control group with P < 0.00001. The results for the incidence of myalgia in the two groups were as follows: P value at 24 h was 0.00018 and at 48 h was 0.0028, respectively. Creatine kinase levels at preoperative and 24 h postoperative periods were 49.47 ± 7.24 in Group D, 53.30 ± 7.98 in Group B and 87.38 ± 15.16 in Group D, and 188.41 ± 33.27 in Group B, respectively. Succinylcholine-induced myalgia has a complex pathophysiology. However, the preemptive use of diclofenac in combination with precurarization can alleviate the incidence and severity of succinylcholine-induced myalgia. Therefore, its use may be considered in routine cases for induction of anesthesia for facilitating laryngoscopy and endotracheal intubation.


Broad support evident for the emerging specialty of orofacial pain.
The emerging field of Orofacial Pain is being considered by the American Dental Association for full status as a new dental specialty. Many recent advances in the neuroscience of orofacial pain have lead to treatments by orofacial pain dentists that provide significant relief for patients with chronic orofacial pain disorders. However, access to this care has been limited leaving many patients to continue to suffer. Subsequently, recent efforts to improve this by developing the field into a specialty have shown broad support among dentists and increased awareness of the benefits this field can provide for dentists and their patients. A recent survey of 805 individuals in the general population who reported having a persistent pain disorder revealed that more than four out of 10 people have yet to find adequate relief, saying their pain is out of control-despite having the pain for more than 5 years and switching doctors at least once. "This survey suggests that there are millions of people living with severe uncontrolled pain," says Russell Portenoy, MD, President of the American Pain Society. "This is a great tragedy. Although not everyone can be helped, it is very likely that most of these patients could benefit if provided with state-of-the-art therapies and improved access to pain specialists when needed." (1). Development of the field of Orofacial Pain into a dental specialty has been motivated primarily by this issue; patients with complex chronic orofacial pain disorders have not been historically treated well by any discipline of health care. Recent studies of chronic orofacial pain patients have found that these patients have a high number of previous clinicians and have endured many years with pain prior to seeing an orofacial pain dentist (2) (Fig. 1). Complex pain patients and the clinicians who see them are often confused about whom they should consult for relief of the painful disorder. Treatment for these patients within the existing structure of dental or medical specialties has been inadequate and millions of patients are left suffering. Insurers are also confused with regard to reimbursement and make decisions to exclude treatment for orofacial pain disorders under both dental and medical policies. However, Dentistry has taken a leading role in health care to address this national problem by developing the field of Orofacial Pain into a dental specialty. A study of dentists and dental specialists have shown that there is a recognized need and broad support for further development of this field into a new dental specialty(3).


Impact of Behavioral Nudges on the Quality of Serious Illness Conversations Among Patients With Cancer: Secondary Analysis of a Randomized Controlled Trial.
Serious Illness Conversations (SICs) are structured conversations between clinicians and patients about prognosis, treatment goals, and end-of-life preferences. Although behavioral interventions may prompt earlier or more frequent SICs, their impact on the quality of SICs is unclear. This was a secondary analysis of a randomized clinical trial (NCT03984773) among 78 clinicians and 14,607 patients with cancer testing the impact of an automated mortality prediction with behavioral nudges to clinicians to prompt more SICs. We analyzed 318 randomly selected SICs matched 1:1 by clinicians (159 control and 159 intervention) to compare the quality of intervention vs. control conversations using a validated codebook. Comprehensiveness of SIC documentation was used as a measure of quality, with higher integer numbers of documented conversation domains corresponding to higher quality conversations. A conversation was classified as high-quality if its score was ≥ 8 of a maximum of 10. Using a noninferiority design, mixed effects regression models with clinician-level random effects were used to assess SIC quality in intervention vs. control groups, concluding noninferiority if the adjusted odds ratio (aOR) was not significantly < 0.9. Baseline characteristics of the control and intervention groups were similar. Intervention SICs were noninferior to control conversations (aOR 0.99; 95% CI, 0.91 to 1.09). The intervention increased the likelihood of addressing patient-clinician relationship (aOR = 1.99; 95% CI, 1.23 to 3.27; P < .01) and decreased the likelihood of addressing family involvement (aOR = 0.56; 95% CI, 0.34 to 0.90; P < .05). A behavioral intervention that increased SIC frequency did not decrease their quality. Behavioral prompts may increase SIC frequency without sacrificing quality.


Relationships between stretch-shortening cycle performance and maximum muscle strength.
This study aimed to examine the relationships between muscle power output using the stretch-shortening cycle (SSC) and maximum strength, as measured by the 1 RM (1 repetition maximum) test and the isokinetic dynamometer under elbow flexion. Sixteen trained, young adult males pulled a constant load of 40% MVC (maximum voluntary elbow flexion contraction) by ballistic elbow flexion under the following two preliminary conditions: 1) the static relaxed muscle state (SR condition) and 2) using the SSC (SSC condition). Muscle power was determined from the product of the pulling velocity and load mass by a power measurement instrument with a rotary encoder. The 1 RM bench press (1RM BP) and isokinetic maximum strength under elbow flexion with the Cybex-325 were measured as indicators of dynamic maximum strength. 1) The early power output exerted under the SSC condition showed a significant and high correlation with the 1 RM BP (r = 0.83), but only moderate correlation with the isokinetic muscle strength (r = 0.50-0.67). 2) The contribution of the 1 RM BP to the early muscle contraction velocity exerted under the SSC condition was large. These results suggested that muscle power exerted using the SSC shows a stronger relationship with maximum muscle strength measured by a 1 RM test rather than isokinetic maximum strength.


Clinical Outcomes Associated With Left Atrial Appendage Occlusion Versus Direct Oral Anticoagulation in Atrial Fibrillation.
This study sought to investigate clinical outcomes associated with left atrial appendage occlusion (LAAO) versus direct oral anticoagulants (DOACs) in patients with high-risk atrial fibrillation (AF). LAAO has been shown to be noninferior to warfarin for stroke prevention in AF. However, anticoagulation with DOACs is now preferred over warfarin as thromboprophylaxis in AF. Patients with AF enrolled in the Amulet Observational Registry (n = 1,088) who had successful LAAO with the Amplatzer Amulet device (n = 1,078) were compared with a propensity score-matched control cohort of incident AF patients (n = 1,184) treated by DOACs identified from Danish national patient registries. Propensity score matching was based on the covariates of the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category) and HAS-BLED (hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol) scores for predicting stroke and bleeding. The primary outcome was a composite of ischemic stroke, major bleeding (Bleeding Academic Research Consortium ≥3), or all-cause mortality, and follow-up was 2 years. AF patients treated with LAAO had a significantly lower risk of the primary composite outcome as compared with patients treated with DOACs (hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.49 to 0.67). Total events and event rates per 100 patient-years were (LAAO vs. DOACs) 256 vs. 461 and 14.5 vs. 25.7, respectively. The risk of ischemic stroke was comparable between groups (HR: 1.11; 95% CI: 0.71 to 1.75), while risk of major bleeding (HR: 0.62; 95% CI: 0.49 to 0.79) and all-cause mortality (HR: 0.53; 95% CI: 0.43 to 0.64) were significantly lower in patients treated with LAAO. Among high-risk AF patients, LAAO in comparison with DOACs may have similar stroke prevention efficacy but lower risk of major bleeding and mortality.


Early detection of bone marrow engraftment by amplification of hypervariable DNA regions.
After allogeneic bone marrow transplantation (BMT) it is important to be able to distinguish between the host and donor origin of cells in order to monitor the engraftment process. However, identifying whether the hematopoietic stem cells are of donor or recipient origin may be a difficult task. DNA studies using Southern blotting techniques or the amplification by PCR of regions in the human genome with high polymorphic neutral sequence variation showing Mendelian inheritance as variable number of tandem repeats (VNTR) can detect the origin of host bone marrow after BMT. We have tried to apply these sensitive systems of detection to the early stages of BMT when small numbers of regenerated cells are available for analysis. We used in vitro polymerase chain reaction (PCR) amplification of three single-locus simple repetitive DNA sequences, all of which vary extensively in their repeat number among different individuals (VNTR D1S80, ApoB, and D17S5), to evaluate post transplant engraftment in six patients who showed no signs of peripheral blood engraftment at 2-3 weeks after transplant. We tested 2 patients with chronic myelogenous leukemia (CML), 2 with B-acute lymphoblastic leukemia (B-ALL), 1 with T-acute lymphoblastic leukemia (T-ALL), and 1 with aplastic anemia (SAA), all in prolonged aplasia following allogeneic bone marrow transplantation (BMT). In a sequential analysis protocol with the different loci, the donor was distinguishable from the recipient in all pairs with at least one of the three markers used. After 16 days (median 16.2; range 15 to 20 days) we found that complete chimerism was present in 5 patients: 4 of donor origin (= engraftment) and one of host origin (= rejection), this last case being one of mixed chimerism. In the 2 cases in which the presence (one complete and one partial) of host DNA was detected, rejection of the donor bone marrow followed, and in 1 patient a second BMT was necessary. The other 4 patients with complete chimerism of donor origin achieved hematological reconstitution and we documented complete engraftment of donor bone marrow a few months later. Utilizing PCR to document early post-transplant engraftment and chimerism in the first month after BMT has the advantage over Southern blotting of being more sensitive and requiring small amounts of sample. It may also be useful for guiding subsequent therapeutic decisions.


A "Ballpark" Assessment of Social Distancing Efficiency in the Early Stages of the COVID-19 Pandemic.
This paper presents an efficiency assessment of social distancing as an internationally adopted measure to tackle the COVID-19 pandemic in 2020. The simple framework adopted for the assessment accounts for two kinds of costs that a society may bear in a pandemic. The first is welfare loss due to infection and its consequences, and the second is welfare loss resulting from a slowdown in economic transactions. We call the first infection costs, and the second economic costs, for convenience in the paper. Efficient social distancing should minimize the sum of these costs. Infection costs are likely to decrease with social distancing at a decreasing rate as intensified social distancing eases pressure on scarce resources for intensive care. Economic costs on the other hand are likely to increase at an increasing rate as extreme slowdown in economic life may entail job losses and business failures. The resulting U-shaped total costs curve implies parity between infection costs and economic costs as a necessary condition for efficiency. In a simplified implementation of the framework, we approximate infection costs by the value of (statistical) lives lost, and economic costs by the gap between the actual gross domestic product (GDP) in 2020 and the potential GDP as predicted by the within-country growth trend during the preceding decade. The results for 158 countries suggest that the global community perhaps reacted with overly strict social distancing measures. The results for the subgroup of high-income countries, however, suggest that these countries were more successful in maintaining the parity between infection and economic costs.


Antidiabetic effects of Tangnaikang on obese Zucker rats and the mechanism.
To observe the effects of Tangnaikang (TNK), a compound traditional Chinese herbal medicine, on glucose metabolism and insulin resistance in obese Zucker rats. Twelve male obese Zucker rats, 6 weeks old, were randomly divided into control group and TNK group (3.24 g/kg) after being fed for 2 weeks. All rats received high-fat diet and 4-week treatment. Body weight and blood glucose were tested every week. Oral glucose tolerance test (OGTT) was performed and fasting insulin level was tested on days 0, 14 and 28. Triglyceride, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and free fatty acids (FFA) were tested on day 28. Glucose infusion rate (GIR) was tested by hyperinsulinemic-euglycemic clamp from day 29. The protein expressions of protein kinase B (Akt), phospho-Akt (p-Akt) (Thr308) and glucose transporter protein 4 (GLUT4) in skeletal muscle and GLUT4 in adipose tissue were measured after hyperinsulinemic-euglycemic clamp test. Compared with the control group, the fed blood glucose level and glucose level of OGTT at 120 min had a significant decline in TNK group on day 28, and TNK caused no alteration of the fasting serum insulin, and the GIR increased significantly in hyperinsulinemic-euglycemic clamp study. Furthermore, TNK increased Akt and p-Akt (Thr308) protein expressions in skeletal muscle and decreased the protein expression of GLUT4 in white adipose tissue. Body weight, and triglyceride, cholesterol, LDL-C and FFA contents were slightly decreased in the TNK group, but there were no statistically significant effects. TNK increases the protein expressions of Akt and p-Akt (Thr308) of the signal transduction pathway to influence the translocation of GLUT4 in skeletal muscle and improves glucose metabolism by reducing insulin resistance.


Assessment of response to neoadjuvant therapy in esophageal cancer: an updated systematic review of diagnostic accuracy of endoscopic ultrasonography and fluorodeoxyglucose positron emission tomography.
For assessing response to neoadjuvant therapy in patients with esophageal cancer, both endoscopic ultrasonography (EUS) and fluorodeoxyglucose positron emission tomography (FDG-PET) are commonly used, and despite few controlled trials, it is not known if one imaging modality is superior to the other. Also, relative diagnostic accuracy of early (during the course of neoadjuvant therapy) and FDG-PET after completion of neoadjuvant therapy has not been reviewed. The aim of this study was to perform a systematic review of published information to compare diagnostic accuracy of EUS and FDG-PET in this setting. A search of the MEDLINE, EMBASE, and Cochrane databases was performed along with a manual search of cross-references of eligible articles. Data on the accuracy of the imaging modalities were compared by constructing summary receiver-operating characteristic curves. Seven studies with EUS and 15 with FDG-PET were included in the final analysis (N= 966). The sensitivity of EUS and FDG-PET ranged from 20 to 100% and 42 to 100%, respectively. The specificity ranged from 36 to 100% and 27 to 100%, respectively. The areas under the curve were 0.86 (95% confidence interval [CI]: 0.77-0.96) for EUS and 0.80 (95% CI: 0.72-0.89) for FDG PET (P= 0.37). The maximum joint sensitivity and specificity (Q* index) values for EUS and FDG-PET were 0.79 (95% CI: 0.70-0.88) and 0.74 (95% CI: 0.66-0.81), respectively (P= 0.38). There was no difference in accuracy between early FDG-PET and FDG-PET after completion of neoadjuvant therapy. EUS and FDG-PET have similar overall diagnostic accuracy for assessment of response to neoadjuvant therapy in patients with esophageal cancer.


The synthesis and antimicrobial activity of some 4-hydroxycoumarin derivatives.
Due to exceptional reactivity of 4-hydroxycoumarin, the synthesis of new coumarin derivatives of dimer and tetramer type has been carried out. The synthesis was carried out from 4-hydroxycoumarin and various aromatic aldehydes. In this way, compounds of the dimer 3,3'-(benzilidene)bis (4-hydroxycoumarin) type, as well as of the tetramer 3,3',3'',3'''-(1,4-dimethylenphenyl)tetra (4-hydroxycoumarin) type were prepared. The newly synthesized derivatives contain different functional groups, and as such they could exhibit microbiological activity. Therefore, we tested the microbiological activity of these derivatives on various species of bacteria and fungi. The tested compounds have shown different activity in terms of growth inhibition of microorganisms. Newly synthesized derivatives exhibit antibacterial activities, manifested as growth inhibition on Gram-positive bacteria types (Bacillus, Staphylococcus), while the activity against Candida was much weaker. The same compound did not show any antimicrobial activity against two Gram-negative bacteria types (Escherichia coli, Pseudomonas aeruginosa). The compound 1 showed the best microbiological activity. The obtained results confirmed its good antibacterial and antimycotic activities against different microorganisms.


Obstructive sleep apnoea in Auckland: diagnosis and treatment.
In 1982 facilities for investigation of patients with sleep disorders were established at Auckland Hospital on a trial basis. Twenty patients with the obstructive sleep apnoea syndrome had been investigated and treated by the end of 1983. All were advised to avoid alcohol and sedatives and the obese patients were encouraged to lose weight. In the more severely affected patients either nasal continuous positive airway pressure or tracheostomy was used. The method of diagnosis and treatment are discussed.


Evaluation of the Clinical Performance of the HPV-Risk Assay Using the VALGENT-3 Panel.
Human papillomavirus (HPV) testing is increasingly being incorporated into cervical cancer screening. The Validation of HPV Genotyping Tests (VALGENT) is a framework designed to evaluate the clinical performance of various HPV tests relative to that of the validated and accepted comparator test in a formalized and uniform manner. The aim of this study was to evaluate the clinical performance of the HPV-Risk assay with samples from the VALGENT-3 panel and to compare its performance to that of the clinically validated Hybrid Capture 2 assay (HC2). The VALGENT-3 panel comprises 1,300 consecutive samples from women participating in routine cervical cancer screening and is enriched with 300 samples from women with abnormal cytology. DNA was extracted from original ThinPrep PreservCyt medium aliquots, and HPV testing was performed using the HPV-Risk assay by investigators blind to the clinical data. HPV prevalence was analyzed, and the clinical performance of the HPV-Risk assay for the detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) and CIN2 or worse (CIN2+) relative to the performance of HC2 was assessed. The sensitivity of the HPV-Risk assay for the detection of CIN3+ was similar to that of HC2 (relative sensitivity, 1.00; 95% confidence interval [CI], 0.95 to 1.05; P = 1.000), but the specificity of the HPV-Risk assay was significantly higher than that of HC2 (relative specificity, 1.02; 95% CI, 1.01 to 1.04; P < 0.001). For the detection of CIN2+, similar results were obtained, with the relative sensitivity being 0.98 (95% CI, 0.93 to 1.02; P = 0.257) and the relative specificity being 1.02 (95% CI, 1.01 to 1.03; P < 0.001). The performance of the HPV-Risk assay for the detection of CIN3+ and CIN2+ was noninferior to that of HC2, with all P values being ≤0.006. In conclusion, the HPV-Risk assay demonstrated noninferiority to the clinically validated HC2 by the use of samples from the VALGENT-3 panel for test validation and comparison.


CD8(+) T cells: foot soldiers of the immune system.
Resting naive CD8(+) T cells have an astounding capacity to react to pathogens by massive expansion and differentiation into cytotoxic effector cells that migrate to all corners of the body to clear the infection. The initial interaction with antigen-presenting cells in the central lymphoid organs drives an orchestrated program of differentiation aimed at producing sufficient numbers of effectors to get the job done without resulting in clonal exhaustion. Interactions with antigen-presenting cells and other immune cells continue at the site of infection to regulate further on-site expansion and differentiation, all with the goal of protecting the host with minimal bystander tissue damage. Here we review recent advances in CD8(+) T cell recognition of antigen in lymphoid as well as in nonlymphoid tissues in the periphery, and how CD8(+) T cell expansion and differentiation are controlled in these contexts.


Sample size calculations for controlled clinical trials using generalized estimating equations (GEE).
Clinical trials with correlated response data based on generalized estimating equations (GEE) have become increasingly popular as they require smaller samples than classical methods that ignore the clustered nature of the data. We have recently derived the recommendation to use the independence estimating equations (IEE) as primary analysis in most controlled clinical trials instead of GEE with estimated correlations. Although several approaches for sample size and power calculation have been proposed, we have shown that most of these procedures are very specific and not as general as required for designing clinical trials. We extended the previously developed SAS macro GEESIZE to overcome this restriction. Specifically, we have added the option of an independence working correlation matrix required for the IEE. Additionally, we have reformulated the hypotheses to allow for coding that includes an intercept term instead of the previously used analysis of variance coding. To demonstrate the validity of GEESIZE we investigate the calculated sample sizes for specific models where closed formulae are available. For illustration, we utilize GEESIZE for planning a new trial on the treatment of hypertension and thereby exemplify its flexibility. We show that our freely available macro is a very general and useful tool for sample size calculation purposes in clinical trials with correlated data.


Rheumatoid arthritis: what do MRI and ultrasound show.
Rheumatoid arthritis is the most common inflammatory arthritis, affecting approximately 1% of the world's population. Its pathogenesis has not been completely understood. However, there is evidence that the disease may involve synovial joints, subchondral bone marrow as well as intra- and extraarticular fat tissue, and may lead to progressive joint destruction and disability. Over the last two decades, significant improvement in its prognosis has been achieved owing to new strategies for disease management, the emergence of new biologic therapies and better utilization of conventional disease-modifying antirheumatic drugs. Prompt diagnosis and appropriate therapy have been recognized as essential for improving clinical outcomes in patients with early rheumatoid arthritis. Despite the potential of ultrasonography and magnetic resonance imaging to visualize all tissues typically involved in the pathogenesis of rheumatoid arthritis, the diagnosis of early disease remains difficult due to limited specificity of findings. This paper summarizes the pathogenesis phenomena of rheumatoid arthritis and describes rheumatoid arthritis-related features of the disease within the synovium, subchondral bone marrow and articular fat tissue on MRI and ultrasound. Moreover, the paper aims to illustrate the significance of MRI and ultrasound findings in rheumatoid arthritis in the diagnosis of subclinical and early inflammation, and the importance of MRI and US in the follow-up and establishing remission. Finally, we also discuss MRI of the spine in rheumatoid arthritis, which may help assess the presence of active inflammation and complications.


Critical role of iodination for T cell recognition of thyroglobulin in experimental murine thyroid autoimmunity.
We have used two clonotypically distinct thyroglobulin (Tg)-specific, I-Ak restricted monoclonal T cell populations to investigate the role of thyroid peroxidase-catalyzed iodination in Tg recognition by autoreactive T cells. The results showed that these T cells could recognize Tg only it it was sufficiently iodinated. Unlike normal mouse Tg, noniodinated mouse Tg was unable to induce significant thyroid lesions but could trigger the production of Tg autoantibodies. In these experiments, the importance of T cell recognition of iodination-related epitopes was emphasized by the inability of serum antibodies to distinguish Tg on the basis of iodine content, whether they were induced with normal or noniodinated Tg. Therefore, thyroid peroxidase-dependent modification of Tg would appear to be central to its recognition by autoreactive T cells and hence its capacity to induce autoimmune thyroid lesions.


The Culture Dish Surface Influences the Phenotype and Cytokine Production of Human Monocyte-Derived Dendritic Cells.
Monocyte-derived dendritic cells (moDC) are an important scientific and clinical source of functional dendritic cells (DC). However, the optimization of the generation process has to date mainly been limited to the variation of soluble factors. In this study, we investigated the impact of the cell culture dish surface on phenotype and cytokine profile. We compared a standard cell culture dish to a non-adherent culture dish for two immunogenic maturation conditions, two tolerogenic conditions, and an unstimulated control. Phenotype, cytokine profile and T cell stimulatory capacity were determined after a 3-day culture. Light microscopy revealed an increase in homotypic cluster formation correlated with the use of non-adherent surfaces, which could be reduced by using blocking antibodies against CD18. All surface markers analyzed showed moderate to strong differences depending on the culture dish surface, including significantly decreased expression of key maturation markers such as CD80, CD86, and CCR7 as well as PD-L1 on cells stimulated with the Jonuleit cytokine cocktail cultured on a non-adherent surface. Significant differences in the secretion of many cytokines were observed, especially for cells stimulated with LPS, with over 10-fold decreased secretion of IL-10, IL12-p40, and TNF-α from the cells cultured on the non-adherent surface. All immunogenic moDC populations showed similar capacity to induce antigen-specific T cells. These results provide evidence that the DC phenotype depends on the surface used during moDC generation. This has important implications for the optimization of DC-based immunotherapy development and underlines that the local surrounding can interfere with the final DC population beyond the soluble factors.


Reproductive and morphometric traits of Macrobrachium amazonicum (Decapoda: Palaemonidae) from the Pantanal, Brazil, suggests initial speciation.
The palaemonid shrimp Macrobrachium amazonicum shows an unusually large geographic range (ca. 4000km across) living in coastal, estuarine, and limnic inland habitats of the upper Amazon, Orinoco, and La Plata basins. This raises doubts whether allopatric, ecologically diverse populations belong to the same species. While shrimps from estuarine and Amazonian habitats have been studied in great detail, very little is known about hololimnetic inland populations. In the present study, biological traits related to growth (maximum body size, fresh weight, morphometric relationships) and reproduction (sex ratio; occurrence of male morphotypes; minimum sexable size; minimum size of ovigerous females; fecundity; egg size), were studied in M amazonicum collected from a pond culture and two natural freshwater habitats (Rio Miranda; Lagoa Baiazinha) in the Pantanal of Mato Grosso do Sul, Brazil. In total, 2270 shrimps were examined (603 males; 1667 females, 157 of these ovigerous). Sex ratio (males:females) was at all sampling sites strongly female-biased, ranging from 0.2-0.6. Maximum body size was larger in natural habitats compared to the pond culture, suggesting reduced growth or a shorter life span under artificial mass rearing conditions. Maximum fecundity observed in our material was 676 eggs, reached by the largest female (TL=65mm; Lagoa Baiazinha). A significant difference between slope parameters of linear regressions describing fecundity, either in terms of numbers of eggs laid or of larvae released, in relation to female fresh weight, indicates egg losses. This may be due in part to a 2.4-fold increase in egg volume occurring during the course of embryonic development, while the available space under the abdomen remains limited. Size-weight relationships differed significantly between males and females, indicating sexspecific morphometric differences. Males appear to have a more slender body shape than females, reaching thus lower weight at equal TL. When reproductive and morphometric traits are compared with literature data from estuarine and inland populations living in the Amazon and Orinoco plains, shrimps from the Pantanal show conspicuous peculiarities differing from other populations: (1) maximum body size is far smaller, suggesting shorter longevity; (2) females are consistently larger than males; (3) different male morphotypes are absent; (4) minimum sexable size and (5) minimum size of ovigerous females are smaller. These traits suggest a heterochronic shift (predisplacement) of sexual maturation and r-selection. In summary, our data show biologically relevant differences in life-history traits of shrimps from the Pantanal compared to M. amazonicum populations in other regions. All these differences persist also in long-term cultures maintained under constant conditions. Altogether, our data support the hypothesis that M amazonicum in the Paraná-Paraguay drainage basin has phylogenetically diverged from allopatric populations that are hydrologically separated by continental watersheds, implying an at least incipient vicariant speciation.


Directed content analysis of Veterans Affairs policy documents: A strategy to guide implementation of a dementia home safety toolkit for Veterans to promote ageing in place.
Older adults' preference to age in place, coupled with an increasing prevalence of dementia, creates an imperative to address home safety risks that occur due to cognitive impairment. Providing caregivers with home safety items and education can facilitate ageing in place for older adults living with dementia. In 2015-2017, we examined barriers and facilitators within 17 policy documents and dementia guidelines of the United States (US) Veterans Health Administration pertinent to implementation of a home safety toolkit (HST) for Veterans living with dementia. The documents were issued from 2000 to 2015. Directed qualitative content analysis of these documents guided by themes from stakeholder interviews revealed two key implementation barriers: a focus on physical rather than cognitive risks when determining medical necessity for home equipment, and a focus on rehabilitation and treatment rather than prevention. Mandates for person-centred care planning, including comprehensive assessment, interdisciplinary collaboration, staff education and a focus on population health in primary care facilitate HST implementation. Content analysis can identify policy-level barriers that slow innovation and facilitators that can increase access to care that support ageing in place.


Caveolae and clathrin-coated vesicles: two possible internalization pathways for IFN-gamma and IFN-gamma receptor.
Interferon-gamma (IFN-gamma) elicits a variety of activities following binding to its cell-surface-specific receptor (IFN-gammaR). This complex formation leads to the activation of the Jak-STAT pathway. Several hypotheses have been proposed to explain the role and location of the receptor and its ligand in the signalling pathway. In vivo as well as in vitro, the present study shows that IFN-gamma and its receptor were internalized in different cellular compartments including cytoplasmic matrix, mitochondria and nucleus. In order to analyse the internalization pathway of IFN-gamma and its receptor, we have study in vivo and in vitro their colocalization with clathrin and caveolin by using double immunogold-labelling experiments using electron microscopy. We demonstrate that IFN-gamma and IFN-gammaR were colocalized in the caveolin-containing structures and the clathrin-coated pits suggesting that both internalization pathways may be used. This indicates that IFN-gamma and IFN-gammaR were internalized by these two different pathways, suggesting two different intracellular routes probably for different target cell-compartments.


Solar-Like M-Class X-ray Flares on Proxima Centauri Observed by the ASCA Satellite.
Because of instrumental sensitivity limits and stellar distances, the types of x-ray flares observable on stars have been intrinsically much more energetic than those on the sun. Such enormous events are a useful extrapolation of the solar phenomenon if the underlying assumption is correct that they form a continuous sequence involving similar physical processes as on the sun. The Advanced Satellite for Cosmology and Astrophysics (ASCA), with its greater sensitivity and high-energy response, is now able to test this hypothesis. Direct comparison with solar flares measured by the x-ray-monitoring Geostationary Operational Environmental Satellites (GOES) is possible. The detection of flares on Proxima Centauri that correspond to GOES M-class events on the sun are reported.


Direct and indirect parental exposure to endocrine disruptors and elevated temperature influences gene expression across generations in a euryhaline model fish.
Aquatic organisms inhabiting polluted waterways face numerous adverse effects, including physiological disruption by endocrine disrupting compounds (EDCs). Little is known about how the temperatures associated with global climate change may influence the response of organisms exposed to EDCs, and the effects that these combined stressors may have on molecular endpoints such as gene expression. We exposed Menidia beryllina (inland silversides) to environmentally relevant concentrations (1 ng/L) of two estrogenic EDCs (bifenthrin and 17α-ethinylestradiol; EE2) at 22 °C and 28 °C. We conducted this experiment over multiple generations to better understand the potential effects to chronically exposed populations in the wild. We exposed adult parental fish (F0) for 14 days prior to spawning of the next generation. F1 larvae were then exposed from fertilization until 21 days post hatch (dph) before being transferred to clean water tanks. F1 larvae were reared to adulthood, then spawned in clean water to test for further effects of parental exposure on offspring (F2 generation). Gene expression was quantified by performing qPCR on F0 and F1 gonads, as well as F1 and F2 larvae. We did not detect any significant differences in the expression of genes measured in the parental or F1 adult gonads. We found that the 28 °C EE2 treatment significantly decreased the expression of nearly all genes measured in the F1 larvae. This pattern was transferred to the F2 generation for expression of the follicle-stimulating hormone receptor (FSHR) gene. Expression of 17β-hydroxysteroid dehydrogenase (17β-HSD) and G protein-coupled receptor 30 (GPR30) revealed changes not measured in the previous generation. Effects of the bifenthrin treatments were not observed until the F2 generation, which were exposed to the chemicals indirectly as germ cells. Our results indicate that effects of EDCs and their interactions with abiotic factors, may not be adequately represented by singular generation testing. These findings will contribute to the determination of the risk of EDC contamination to organisms inhabiting contaminated waterways under changing temperature regimes.


Pulmonary valvuloplasty as an alternative to surgery in the pediatric patient: implications for nursing.
Recent innovations in the use of balloon catheters to dilate stenosis have made it possible to successfully perform balloon valvuloplasty (BV) on stenotic intracardiac valves. BV is fast becoming the treatment of choice for isolated valvular pulmonary stenosis (IVPS) in pediatric patients. IVPS and other obstructive lesions involving the right ventricle and pulmonary arteries occur in 25% to 30% of all persons with congenital heart disease. Current data suggest that use of BV for IVPS provides both short- and long-term hemodynamic relief and eliminates the need for open heart surgery. BV is also being used for other forms of congenital heart disease. Therefore, it is important for nurses in the pediatric setting to be aware of this technique and its implications. We review the anatomy, physiology, and clinical features of IVPS, the valvuloplasty procedure, and the nursing plan of care relevant to it.


Are global tuberculosis control targets overlooking an essential indicator? Prolonged delays to diagnosis despite high case detection rates in Yunnan, China.
Delay in treating active tuberculosis (TB) impedes disease control by allowing ongoing transmission, and may explain the unexpectedly modest declines in global TB incidence. Even though China has achieved TB control targets under the global Directly Observed Treatment, Short course (DOTS) strategy, TB prevalence in western provinces, including Yunnan, is not decreasing. This cross-sectional study investigates whether prolonged delay in identifying and correctly treating TB patients, which is not routinely monitored, persists even when there is a well-functioning TB control programme and global targets are being met. Records of adult smear-positive pulmonary TB patients diagnosed with between 2006 and 2013 were extracted from the Yunnan Centre for Disease Control electronic database, which contains information on the entire population of TB patients managed across 129 diagnostic centres. Delay was investigated at three stages: delay to DOTS facility (period between symptom onset and first visit to at a CDC unit providing standardized treatment); delay to TB confirmation (period between reaching a CDC unit and confirmation of smear-positive TB) and delay to treatment (period between confirmation of TB and initiation of treatment). Data from 76 486 patients was analysed. Delay to reaching a DOTS facility was by far the largest contributor to total delay to treatment initiation. The median delay to reaching a DOTS facility, to TB confirmation and to treatment was 57 days (IQR 25-112), 2 days (IQR 1-6) and 1 day (IQR 0-1) respectively. Prolonged delays to reaching a facility providing standardized TB care occurred in a substantial subset of the population despite all TB control targets being met; overall, 32% (24 676) of patients experienced a delay of more than 90 days to reaching a DOTS facility. Policies that focus on reducing delays in accessing appropriate health services, rather than only on increasing overall case-detection rates, may result in greater progress towards reducing TB incidence.