Miracle-dz/UniFAR-FTUs huggingface dataset:
When a desired home death does not occur: the consequences of broken promises.

BACKGROUND Evidence shows that most people prefer to die at home; however, the majority of expected deaths occur away from home. Although home deaths require family caregiver (FCG) commitment and care, we understand very little about their experiences in this context. AIM The study's aim was to gain a better understanding of the experiences of FCGs when circumstances prevented a desired home death for a family member with advanced cancer. DESIGN An interpretive description approach was used. Data collection involved semistructured interviews. Field notes and reflective journaling aided interpretive and analytical processes. SETTING/PARTICIPANTS The study was conducted in western Canada and included 18 bereaved FCGs. RESULTS FCGs were committed to the promises made to care for their family member at home until death. These promises were challenged by a lack of preparedness for caregiving, difficulty accessing professional support and information, and frustration with the inadequate help they received. The events that precipitated dying family members leaving their home for hospital or hospice were unexpected and often influenced by FCGs' lack of situation-specific knowledge and ability to cope with complex caregiving responsibilities. FCGs found it extremely challenging to reconcile with breaking their promise to care at home until death and many were unable to do so. CONCLUSIONS FCGs' despair about not being able to keep their promise for a home death was related to complicated bereavement. Prospective studies of the experiences of FCGs who are aiming for home deaths are needed to identify both short- and long-term interventions to effectively support death at home.
Sex effects in prepulse inhibition and facilitation of the acoustic startle response: implications for pharmacological and treatment studies

Prepulse inhibition (PPI) refers to the reduction in the response amplitude to a startling stimuli (pulse) if it is preceded (i.e. 30-500 ms) by a weak stimulus (prepulse). If the time interval between the prepulse and pulse is more than 500 ms, then an increase in this response amplitude can be seen, termed prepulse facilitation (PPF). PPI is thought to represent an operational index of sensorimotor function whereas PPF is thought to reflect, at least to some degree, sustained attention. Interestingly, PPI is found to be sexually dimorphic, with men exhibiting more PPI than women when subjects are tested without regard to where they are in the menstrual cycle, and to be impaired in several neuropsychiatric disorders known to exhibit sex differences in their clinical presentation. PPF has received relatively less attention in both normal and clinical studies. This study examined sex differences in both PPI and PPF in 62 healthy subjects (34 women, 28 men) using a range of prepulse-to-pulse intervals to elicit PPI (30, 60, 120, 240 and 480 ms) and PPF (1000 and 2000 ms). Men showed higher PPI than women but women showed higher PPF compared to men. These results suggest that reduced PPI in healthy women is not a simple reduction but rather a shift of the inhibition/facilitation curve in the direction of facilitation in women, relative to men. Future studies investigating pharmacological and treatment effects using a prepulse modification paradigm in normal and clinical populations of both sexes would benefit from an examination of sex effects and assessments of both PPI and PPF.
Biochemical, Biophysical, and Functional Characterization of Bacterially Expressed and Refolded Receptor Binding Domain ofPlasmodium vivax Duffy-binding Protein*

Invasion of erythrocytes by malaria parasites is mediated by specific molecular interactions. Plasmodium vivax is completely dependent on interaction with the Duffy blood group antigen to invade human erythrocytes. The P. vivaxDuffy-binding protein, which binds the Duffy antigen during invasion, belongs to a family of erythrocyte-binding proteins that also includesPlasmodium falciparum sialic acid binding protein andPlasmodium knowlesi Duffy binding protein. The receptor binding domains of these proteins lie in a conserved, N-terminal, cysteine-rich region, region II, found in each of these proteins. Here, we have expressed P. vivax region II (PvRII), the P. vivax Duffy binding domain, in Escherichia coli. Recombinant PvRII is incorrectly folded and accumulates in inclusion bodies. We have developed methods to refold and purify recombinant PvRII in its functional conformation. Biochemical, biophysical, and functional characterization confirms that recombinant PvRII is pure, homogeneous, and functionally active in that it binds Duffy-positive human erythrocytes with specificity. Refolded PvRII is highly immunogenic and elicits high titer antibodies that can inhibit binding of P. vivax Duffy-binding protein to erythrocytes, providing support for its development as a vaccine candidate forP. vivax malaria. Development of methods to produce functionally active recombinant PvRII is an important step for structural studies as well as vaccine development.
Glycerophosphocholine Catabolism as a New Route for Choline Formation for Phosphatidylcholine Synthesis by the Kennedy Pathway*

In eukaryotes, neuropathy target esterase (Nte1p in yeast) deacylates phosphatidylcholine derived exclusively from the CDP-choline pathway to produce glycerophosphocholine (GroPCho) and release two fatty acids. The metabolic fate of GroPCho in eukaryotic cells is currently not known. Saccharomyces cerevisiae contains two open reading frames predicted to contain glycerophosphodiester phosphodiesterase domains, YPL110c and YPL206c. Pulse-chase experiments were conducted to monitor GroPCho metabolic fate under conditions known to alter CDP-choline pathway flux and consequently produce different rates of formation of GroPCho. From this analysis, it was revealed that GroPCho was metabolized to choline, with this choline serving as substrate for renewed synthesis of phosphatidylcholine. YPL110c played the major role in this metabolic pathway. To extend and confirm the metabolic studies, the ability of the ypl110cΔ and ypl206cΔ strains to utilize exogenous GroPCho or glycerophosphoinositol as the sole source of phosphate was analyzed. Consistent with our metabolic profiling, the ypl206cΔ strain grew on both substrates with a similar rate to wild type, whereas the ypl110cΔ strain grew very poorly on GroPCho and with moderately reduced growth on glycerophosphoinositol.
Measurement of surgical wait times in a universal health care system.

INTRODUCTION Reported increases in surgical wait times for cancer have intensified the focus on this quality of health care indicator and have created a very public, concerted effort by providers to decrease wait times for cancer surgery in Ontario. Delays in access to health care are multifactorial and their measurement from existing administrative databases can lack pertinent detail. The purpose of our study was to use a real-time surgery-booking software program to examine surgical wait times at a single centre. METHODS The real-time wait list management system Axcess.Rx has been used exclusively by the department of urology at the Kingston General Hospital to book all nonemergency surgery for 4 years. We reviewed the length of time from the decision to perform surgery to the actual date of surgery for patients in our group urological practice. Variables thought to be potentially important in predicting wait time were also collected, including the surgeon's assessment of urgency, the type of procedure (i.e., diagnostic, minor cancer, major cancer, minor benign, major benign), age and sex of the patient, inpatient versus outpatient status and year of surgery. Analysis was planned a priori to determine factors that affected wait time by using multivariate analysis to analyze variables that were significant in univariate analysis. RESULTS There were 960 operations for cancer and 1654 for benign conditions performed during the evaluation period. The overall mean wait time was 36 days for cancer and 47 days for benign conditions, respectively. The mean wait time for cancer surgery reached a nadir in 2004 at 29.9 days and subsequently increased every year, reaching 56 days in 2007. In comparison, benign surgery reached a nadir wait time of 33.7 days in 2004 and in 2007 reached 74 days at our institution. Multivariate analysis revealed that the year of surgery was still a significant predictor of wait time. Urgency score, type of procedure and inpatient versus outpatient status were also predictive of wait time. CONCLUSION The application of a prospectively collected data set is an effective and important tool to measure and subsequently examine surgical wait times. This tool has been essential to the accurate assessment of the effect of resource allocation on wait times for priority and nonpriority surgical programs within a discipline. Such tools are necessary to more fully assess and follow wait times at an institution or across a region.
Optimal Multiband Cooperative Spectrum Sensing with Random Interruptions

Introducing random interruptions in the cooperation of the sensing nodes with the fusion center is a new approach to increase the efficiency of the centralized cooperative spectrum sensing in cognitive radio (CR) networks. In this paper, we extend this approach to the multiband cooperative spectrum sensing. Specifically, first, we formally show how to incorporate the random interruptions in a multiband joint detection scenario. Next, we formulate the system performance in terms of the \emph{aggregate opportunistic throughput} of the CR network and the \emph{aggregate interference} experienced by the primary users. Then, based on these metrics, we formulate the system performance optimization subject to a constraint on the energy and signal processing resources consumed in the mutiband cooperative sensing. Finally, we demonstrate the effectiveness of the proposed method and optimization via computer simulations.
Histopathological analysis of infiltrating T cell subsets in acute T cell-mediated rejection in the kidney transplant

AIM To compare the differential immune T cell subset composition in patients with acute T cell-mediated rejection in the kidney transplant with subset composition in the absence of rejection, and to explore the association of their respective immune profiles with kidney transplant outcomes. METHODS A pilot cross-sectional histopathological analysis of the immune infiltrate was performed using immunohistochemistry in a cohort of 14 patients with acute T cell-mediated rejection in the kidney transplant and 7 kidney transplant patients with no rejection subjected to biopsy to investigate acute kidney transplant dysfunction. All patients were recruited consecutively from 2012 to 2014 at the Singapore General Hospital. Association of the immune infiltrates with kidney transplant outcomes at up to 54 mo of follow up was also explored prospectively. RESULTS In comparison to the absence of rejection, acute T cell-mediated rejection in the kidney transplant was characterised by numerical dominance of cytotoxic T lymphocytes over Foxp3+ regulatory T cells, but did not reach statistical significance owing to the small sample size in our pilot study. There was no obvious difference in absolute numbers of infiltrating cytotoxic T lymphocytes, Foxp3+ regulatory T cells and Th17 cells between the two patient groups when quantified separately. Our exploratory analysis on associations of T cell subset quantifications with kidney transplant outcomes revealed that the degree of Th17 cell infiltration was significantly associated with shorter time to doubling of creatinine and shorter time to transplant loss. CONCLUSION Although this was a small pilot study, results support our suspicion that in kidney transplant patients the immune balance in acute T cell-mediated rejection is tilted towards the pro-rejection forces and prompt larger and more sophisticated studies.
Changes in Gait Symmetry and Velocity After Stroke: A Cross-Sectional Study From Weeks to Years After Stroke

Background. There is little information about the quality of gait in the years following stroke. Long-term changes in mobility, using global indices of function, suggest a decline well after initial rehabilitation. However, global indices of mobility do not reveal more specific changes in walking competency or underlying gait-specific impairment. Objectives. The authors used a cross-sectional design with gait-specific measures (velocity and symmetry) to investigate whether deterioration in gait occurs over the long term poststroke. Methods. Data were abstracted from a standardized database containing clinical assessments and spatiotemporal gait analyses for 171 individuals with stroke. Velocity and 3 expressions of symmetry ratios (swing time, stance time, and step length) were calculated for each individual; they were then assigned to 1 of the 5 following groups: 0 to 3, 3 to 12, 12 to 24, 24 to 48, and >48 months poststroke. Results. Swing time, stance time, and step length symmetry demonstrated a systematic linear trend toward greater asymmetry in groups in the later stages poststroke, whereas velocity, neurological deficit, and lower-extremity (LE) motor impairment did not. Conclusions. The quality of gait, as measured by spatial and temporal symmetry, appears to worsen in later years. These results suggest a dissociation between quantitative measures of gait, such as velocity versus symmetry, and that these parameters may measure independent features. A longitudinal study is needed to confirm the presence and to interpret the clinical meaning of a long-term decline in specific parameters of poststroke gait.
Disruption of the Small-Intestine Mucosal Barrier After Intestinal Occlusion: A Study with Light and Electron Microscopy

It is known that the gut may serve as a reservoir for various microorganisms, which under specific circumstances may intrude into the systemic circulation, causing systemic infections. The aim of the present study was to estimate the "critical time" of disruption of the small-intestine mucosal barrier in conditions of experimentally induced intestinal occlusion, based on the histopathological alterations observed under light and electron microscopy. Forty rabbits underwent small-intestine obstruction through ligation with a nonabsorbable suture. Blood cultures from portal vein and inferior vena cava, as well as cultures from the peritoneal fluid, a hepatic fragment, and a mesenteric lymph node, were obtained before the ligation (0 h). The same cultures were repeated at 4 and 8 h (group A, 20 rabbits) and at 6 and 12 h after the ligation (group B, 20 rabbits). Small-intestine specimens proximal to the occlusion were taken for examination under the optic and electronic microscope in the same time intervals. Five of 20 rabbits of group A died within 4 h and 6 of 20 rabbits of group B died within 6 h after the operation. All anaerobic cultures were negative. All aerobic cultures that became positive developed Escherichia coli colonies. Intestinal epithelium of dead animals was transformed to cuboid with destruction of goblet cells and alteration in secretion of acid polysaccharides. The mucosal appearance of all rabbits that survived 12 hours after ligation was the same. The disruption of the mucosal barrier begins 4 h after complete intestinal occlusion. At 12 h after complete intestinal occlusion, the disruption is total with different degrees of severity.
Electron bridging dihydrogen bond in the imidazole-contained anion derivatives.

The large contact distance of electron bridging dihydrogen bond (EBDB), which is over 2.4 A, is the most prominent characteristic for the imidazole-contained anion derivatives. The elongation of N-H bond and the shortening of H.H distance can be observed upon hydration and hydrogenation. Transformation from EBDB to dissociative H2 is convenient upon sequential hydrogenation. The H.H distance decreases with the enhancement of the electronegativity of the heavy atom which contacts directly with one of these two hydrogen atoms. NMR shielding of the bonding N varies significantly upon hydration and hydrogenation. The spin-spin coupling constants, 1J(H-H), is dominated predominantly by the paramagnetic spin-orbit and diamagnetic spin-orbit contributions instead of the Fermi-contact term. Enhancement of electronegativity of the heavy atom leads to the increase of 1J(H-H) coupling constants. The stabilization is enhanced upon hydration predominantly for the formation of O-H.N H bond, while it is reversed upon hydrogenation for the cleavage of big pi bond, Pi5(6). Enhancement of the stability is demonstrated by the increase of stabilization energy and vertical electron detachment energy with the electronegativity of the heavy atom. The dominant contributions for the formation of such electron bridging dihydrogen bond are the high polarity of each fragment, large electron density between two fragments, and strong bonding interaction of the bridging electron with H(N) atoms. The H.H interaction can be formed by X-Hdelta+ and Hdelta- -Y polar molecules in Hdelta+. Hdelta- and Hdelta+. e.Hdelta+ of two forms.
Kaposi’s Sarcoma-Associated Herpesvirus Encodes a bZIP Protein with Homology to BZLF1 of Epstein-Barr Virus

ABSTRACT Kaposi’s sarcoma-associated herpesvirus (KSHV) is a recently discovered human gamma herpesvirus strongly implicated in AIDS-related neoplasms. We report here the identification in the KSHV genome of a gene for a protein designated K-bZIP and belonging to the basic-leucine zipper (bZIP) family of transcription factors. K-bZIP shows significant homology to BZLF1, which plays a key role in the replication and reactivation of Epstein-Barr virus. K-bZIP is a homodimerizing protein of 237 amino acids with a prototypic bZIP domain at the C terminus. The N-terminal portion of K-bZIP is derived from the K8 open reading frame which, through in-frame splicing, adjoins the ZIP domain. This structure was revealed by rapid analysis of cDNA ends, followed by cloning of the entire cDNA. A 1.35-kb transcript encoding K-bZIP was detected in BCBL-1 cells treated with 12-O-tetradecanoylphorbol-13-acetate. The synthesis of this transcript was blocked by the protein synthesis inhibitor cycloheximide but not by the viral DNA synthesis inhibitor phosphonoacetate, a result which classifies it as an early lytic gene. RNase protection analysis further mapped the major transcription start site for the 1.35-kb K-bZIP mRNA and identified two other splice variants which encode proteins with the N-terminal portion of K-bZIP but lacking the C-terminal ZIP domain. Full-length K-bZIP forms dimers with itself, and the C terminus encompassing the ZIP domain is required for this process. Our studies set the stage for understanding the role of K-bZIP in the replication and reactivation of the KSHV genome.
Non‐specificity of chloride channel blockers in rat cerebral arteries: block of the L‐type calcium channel

1 The effects of chloride channel blockers on pressure‐induced constriction, K+‐induced force, and whole‐cell calcium channel currents were tested in rat cerebral arteries using isobaric and isometric myography, and patch clamp. 2 Under isobaric conditions at 75 mmHg, NPPB), a chloride channel blocker, reversibly depressed the myogenic constriction with an IC50 of 32.8 ± 0.52 μm (mean ± s.e.m., n= 5). Blockers of Ca2+‐activated chloride channels, flufenamic acid (100 μm) and 9‐AC; 1 mm), and the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel blocker, glibenclamide (100 μm), were without effect in this tissue (n= 3). 3 Under isobaric conditions at 20 mmHg, 37 °C, raising [K+]o to 45 mm induced a constriction which was unaffected by 100 μm NPPB (n= 4). In contrast, at 75 mmHg and 18‐21 °C, 100 μm NPPB completely and reversibly blocked a 45 mm K+‐induced constriction (n= 3). 4 Under isometric conditions, NPPB reversibly depressed a 45 mm K+‐induced force with an IC50 of 10.0 ± 0.76 μm (mean ± s.e.m., n= 5). IAA‐94), another chloride channel blocker, depressed the K+‐induced force with an IC50 of 17.0 ± 1.2 μm (mean ± s.e.m., n= 4). 5 Using whole‐cell patch clamp, 100 μm NPPB or 200 μm IAA‐94 blocked calcium channel currents carried by 10 mm Ba2+ by 79.1 ± 1.7 and 39.8 ± 7.0 %, respectively (mean ± s.e.m., n= 6). 6 In summary, chloride channel blockers depress calcium channel currents in rat cerebral arteries, which could contribute to a reduction in myogenic contraction.
COMPARISONS BETWEEN PSYCHOTROPIC DRUGS: MUST THE RISK OF SIDE EFFECTS DICTATE OUR PRACTICES?

Abstract Objectives: Recently, SOHO and CATIE’s studies in the field of schizophrenic disorders asserted that molecules apparently showing the most side-effects are not only the most effective but also lead to the least changes in treatments. Can we generalise this assertion to other domains of pharmacological treatments, such as in mood and anxiety disorders ? And, more generally, do we possess information about comparison between different types of molecules in these different fields. Methods: Review of the literature (medline – psycinfo – psycarticles) addressing these three psychiatric disorders, and comparing efficacy of treatments, or cost-effectiveness studies. Results: Although there is a plethora of publications about the efficacy of given molecules vs. placebo, studies comparing molecules are scarce, and studies on cost-effectiveness in natural environments are even more scarce. Independently of the type of disorders under study, the last few years’ efforts to completely limit side effects seem to have resulted in a loss of efficacy. Moreover, the previously held hypothesis suggesting that the fewer the side effects, the lesser the need to change treatment has not been confirmed. The duration of a treatment is more dependent upon its efficacy than on other variables. Conclusions: Clinicians cannot determine the absence of noxiousness of a molecule as their primary criterion of choice. In contrast, they should carefully balance side effects and efficacy. In Psychiatry, there is a lack of studies about costeffectiveness in natural environments.
Manifestation and persistence of Pig‐a mutant red blood cells in C57BL/6 mice following single and split doses of N‐ethyl‐N‐nitrosourea

Treating rats with single doses of N‐ethyl‐N‐nitrosourea (ENU) results in a time‐dependent accumulation of Pig‐a‐mutant phenotype peripheral red blood cells (RBCs), reaching a plateau at about 6‐weeks posttreatment, with the response persisting for at least 26 weeks. In the present study, groups of 5 C57BL/6 male mice were administered single i.p. doses of up to 140 mg/kg ENU, and blood samples were collected up to 26 weeks posttreatment. The samples were analyzed by flow cytometry for the frequency of CD24‐deficient (presumed Pig‐a mutant) reticulocytes (RETs) and total RBCs; micronucleated RET frequencies were evaluated at 1 day posttreatment. Mean Pig‐a mutant frequencies and micronucleated RET frequencies increased in a dose‐responsive manner, with maximum Pig‐a frequencies in RETs and RBCs observed at Week 2 and Week 4 posttreatment, respectively. Mutant frequencies in RETs and RBCs generally decreased slowly with time after reaching their maxima. In a second experiment, groups of five male C57BL/6 mice were given single i.p. injections of 8, 32, or 160 mg/kg ENU, or four weekly doses of 8 or 40 mg/kg ENU (split doses totaling 32 and 160 mg/kg, respectively). In each case the maximum RET and RBC mutant frequencies produced by the split doses were similar to but not as great as the mutant frequencies produced by the equivalent single doses. The data indicate that ENU‐induced Pig‐a mutant RBC frequencies accumulate in mice as they do in rats; however, mice and rats differ in the manifestation kinetics and the persistence of the responses. © Environ. Mol. Mutagen. 2011. Published 2011 Wiley‐Liss, Inc.