Miracle-dz/UniFAR-FTUs huggingface dataset:
Rehabilitation after spinal cord injury and the influence of the professional's support (or lack thereof).

AIM AND OBJECTIVES To investigate how spinal cord injured patients struggle with their rehabilitation and how they feel that the professionals influence this process. BACKGROUND Rehabilitation after a spinal cord injury is a long and arduous process during which the patient needs much support. Some patients lack adequate support from the professionals. This makes it pertinent to investigate the processes patients go through to get on with their lives and the influence professionals have. DESIGN A phenomenological-hermeneutic study with a narrative approach using Ricoeur's theory. METHOD A purposeful and consecutive sample of 12 newly injured, adult Danish-speaking patients previously living a normal life were observed 7-12 times and interviewed six or seven times over two years. RESULTS The patients regained meaning and got on with life through resolute fighting for a meaningful life. We found three patterns of fight; the patients fought with themselves together with the professionals (pattern I). If consensus about the goals and pathway broke down and was not re-established, this fight could turn into a fight against the professionals (pattern II). This would, in turn, cause the patients to fight against themselves. A third pattern (III) was that the patients turned away, either going their own way or suppressing themselves by adapting to the professionals' views. In either case, the patients would feel being left on their own. CONCLUSION When the patient and professionals agreed on the way forward, the patient experienced the professionals as supportive. However, if the patient's goals were not consistent with the professionals' views, the patient felt that the professionals withdrew their support. RELEVANCE TO CLINICAL PRACTICE If the professional were able to maintain consensus with the patient, they contributed to the patient's process of regaining meaning.
Intergroup conflicts among chimpanzees in Taï National Park: lethal violence and the female perspective

Intercommunity aggression in chimpanzees and primitive warfare in humans possess striking similarities, such as the common occurrence of large male coalitions, systematic control of territory boundaries, and lethal attacks on isolated individuals from neighboring groups. However, an important apparent contrast is the absence of recurrent peaceful interactions between neighboring groups of chimpanzees. We observed a remarkable range of behavior in intergroup encounters among three habituated communities of chimpanzees in Taï National Park, Côte d'Ivoire. Lethal attacks are documented in these study groups for the first time, as well as year‐long exchanges of parous adult females and peaceful intergroup visits of mothers with infants. Demographic factors, including group size and number of adult males, are shown to affect the nature of intergroup interactions in ways not considered previously. A reconsideration of the difference in intergroup interactions between eastern and western chimpanzees is proposed including a more important consideration of the female's perspective. The inclusion of the new complexities in intergroup interactions in chimpanzees allows new parallels to be drawn with the evolution of primitive warfare in humans. Am. J. Primatol. 70:519–532, 2008. © 2008 Wiley‐Liss, Inc.
Mechanism of [4Fe-4S](Cys)4 Cluster Nitrosylation Is Conserved among NO-responsive Regulators*

Background: Fumarate nitrate reduction (FNR) regulator, the master switch between aerobic and anaerobic respiration, responds in vivo to nitric oxide (NO). Results: [4Fe-4S] FNR reacts rapidly with eight NO molecules in a complex, multistep reaction. Conclusion: FNR nitrosylation is remarkably similar to that of WhiB-like proteins. Significance: A common mechanism of nitrosylation exists for phylogenetically unrelated iron-sulfur regulatory proteins. The Fumarate nitrate reduction (FNR) regulator from Escherichia coli controls expression of >300 genes in response to O2 through reaction with its [4Fe-4S] cluster cofactor. FNR is the master switch for the transition between anaerobic and aerobic respiration. In response to physiological concentrations of nitric oxide (NO), FNR also regulates genes, including the nitrate reductase (nar) operon, a major source of endogenous cellular NO, and hmp, which encodes an NO-detoxifying enzyme. Here we show that the [4Fe-4S] cluster of FNR reacts rapidly in a multiphasic reaction with eight NO molecules. Oxidation of cluster sulfide ions (S2−) to sulfane (S0) occurs, some of which remains associated with the protein as Cys persulfide. The nitrosylation products are similar to a pair of dinuclear dinitrosyl iron complexes, [Fe(I)2(NO)4(Cys)2]0, known as Roussin's red ester. A similar reactivity with NO was reported for the Wbl family of [4Fe-4S]-containing proteins found only in actinomycetes, such as Streptomyces and Mycobacteria. These results show that NO reacts via a common mechanism with [4Fe-4S] clusters in phylogenetically unrelated regulatory proteins that, although coordinated by four Cys residues, have different cluster environments. The reactivity of E. coli FNR toward NO, in addition to its sensitivity toward O2, is part of a hierarchal network that monitors, and responds to, NO, both endogenously generated and exogenously derived.
Cleavage Activation of Human-adapted Influenza Virus Subtypes by Kallikrein-related Peptidases 5 and 12*

Background: Cleavage of the influenza HA precursor by host proteases is a critical step in the virus life cycle. Results: The airway-secreted proteases kallikrein 5 and kallikrein 12 were found to cleave and activate influenza HA. Conclusion: Each peptidase had distinct preferences for particular human-adapted influenza viruses. Significance: Identification of these HA-cleaving peptidases aids in our understanding of host proteases involved in influenza infection. A critical step in the influenza virus replication cycle is the cleavage activation of the HA precursor. Cleavage activation of influenza HA enables fusion with the host endosome, allowing for release of the viral genome into the host cell. To date, studies have determined that HA activation is driven by trypsin-like host cell proteases, as well as yet to be identified bacterial proteases. Although the number of host proteases that can activate HA is growing, there is still uncertainty regarding which secreted proteases are able to support multicycle replication of influenza. In this study, we have determined that the kallikrein-related peptidases 5 and 12 are secreted from the human respiratory tract and have the ability to cleave and activate HA from the H1, H2, and H3 subtypes. Each peptidase appears to have a preference for particular influenza subtypes, with kallikrein 5 cleaving the H1 and H3 subtypes most efficiently and kallikrein 12 cleaving the H1 and H2 subtypes most efficiently. Cleavage analysis using HA cleavage site peptide mimics revealed that the amino acids neighboring the arginine cleavage site affect cleavage efficiency. Additionally, the thrombolytic zymogens plasminogen, urokinase, and plasma kallikrein have all been shown to cleave and activate influenza but are found circulating mainly as inactive precursors. Kallikrein 5 and kallikrein 12 were examined for their ability to activate the thrombolytic zymogens, and both resulted in activation of each zymogen, with kallikrein 12 being a more potent activator. Activation of the thrombolytic zymogens may therefore allow for both direct and indirect activation of the HA of human-adapted influenza viruses by kallikrein 5 and kallikrein 12.
EFFECTS OF THE HEXANE EXTRACT OF MONDIA WHITEI ON THE REPRODUCTIVE ORGANS OF MALE RAT.

The present study investigates the effects induced by the long term oral administration of the hexane extract of the dried roots of Mondia whitei at doses of 500 and 1000 mg/kg b.w. on body and organ weights, biochemical (cholesterol, total proteins), haematological (WBC, RBC, haematocrit) and physiological (mechanical response of vas deferens to Norepinephrine) parameters of rats treated for 30 days. Results showed that Mondia whitei did not affect the body and testes weights of rats. At high dose (1000 mg/kg b.w), there was a significant (p<0.05) increase of the relative weights of the caput epididymis, ventral prostate and seminal vesicle whereas at low dose (500 mg/kg b.w), there were growth of the ventral prostate and decrease in the relative weight of the proximal vas deferens as compared with control rats. At all doses, intratesticular cholesterol was decreased, serum and tissue total protein contents increased whilst the haematological variables were within the normal range. Norepinephrine (0.114-3.648 µM) produced concentration-dependent contraction of the vas deferens of rats treated with 500 mg/kg b.w and 1000 mg/kg b.w for 30 days. In rats allowed a washout period of 30 days, except the relative proximal vas deferens where a significant decrease (P < 0.001) was noticed, no change was recorded. These findings give evidence of the reversible androgenic effect of Mondia whitei and partially support its folk use as aphrodisiac.
The influence of age on fecal steroid hormone levels in male Budongo Forest chimpanzees (Pan troglodytes schweinfurthii)

Potential interactions between age and endocrinological functioning have been understudied in wild ape populations. Therefore, we examined the relationship between age and the secretion of androgens and glucocorticoids in 15 juvenile, subadult, and adult male chimpanzees (Pan troglodytes schweinfurthii) free ranging in the Budongo Forest of Uganda. One hundred and nine fecal samples were opportunistically collected, between 07:30 and 13:30 hr, during the wet season. Fecal samples were preserved, by oven drying, and steroid content extracted before radioimmunoassay for dehydroepiandrosterone‐sulfate (DHEA‐S), testosterone (TEST), cortisol (CORT), and corticosterone (CCT). Employing indexes of age as predictive factors, linear mixed‐effects modeling and non‐parametric statistical comparisons of fecal steroid levels were conducted. Age was observed to significantly influence the production of both glucocorticoids and androgens in male Budongo Forest chimpanzees. Basically, whereas TEST and CORT increased, DHEA‐S and CCT levels slightly declined as animals matured. Am. J. Primatol. 70:661–669, 2008. © 2008 Wiley‐Liss, Inc.
Dispersal among male ring‐tailed lemurs (Lemur catta) on St. Catherines Island

Male dispersal patterns were analyzed across a nine‐year period in a population of ring‐tailed lemurs (Lemur catta) on St. Catherines Island (SCI), USA, to evaluate two ultimate explanations for male dispersal: inbreeding avoidance and intrasexual mating competition. As part of this analysis, we also compared patterns of dispersal at this site with data from wild populations. Overall, we found that patterns of male intertroop movement on SCI are similar to the wild with respect to the frequency and seasonality of male transfer. In Madagascar, males move between groups every 3.1–3.5 years [Sussman, International Journal of Primatol 13:395–413, 1992; Koyama et al., Primates 43:291–314, 2002] as compared with every 3.2 years on SCI. The majority of transfers on SCI occurred during the birth season, as occurs at one site in Madagascar, Berenty [Budnitz & Dainis, Lemur biology. New York: Plenum Press, p 219–235, 1975; Jones, Folia Primatologica 40:145–160, 1983]. One difference is that males perform natal transfers 1–2 years earlier on SCI than in the wild, which may be related to food provisioning on SCI. Males never transferred back into their natal troops, which is remarkable given the small number of groups on SCI. Although this pattern of movement can indicate inbreeding avoidance by males, the fact that male troop tenure was in many cases long enough to overlap with the sexual maturation of potential daughters did not support the inbreeding avoidance hypothesis for male secondary dispersal. Instead, the intrasexual competition hypothesis was strongly supported, because males were significantly more likely to transfer into groups having fewer adult males and a more favorable sex ratio than their pretransfer groups. Males therefore appear to be bypassing groups in which they would experience a greater degree of intrasexual mating competition during the breeding season. Am. J. Primatol. 70:650–660, 2008. © 2008 Wiley‐Liss, Inc.
Tumor-derived Mutations in the Gene Associated with Retinoid Interferon-induced Mortality (GRIM-19) Disrupt Its Anti-signal Transducer and Activator of Transcription 3 (STAT3) Activity and Promote Oncogenesis*

Background: Aberrantly active STAT3 promotes tumorigenesis. GRIM-19 binds to STAT3 and inhibits its growth promotion. Results: We identified three mutations in the GRIM-19 gene that failed to block STAT3-dependent gene expression and tumor development. Conclusion: GRIM-19 mutations unleash STAT3 activity to promote tumor growth. Significance: This study identifies a new mechanism by which normal cells acquire cancerous properties. The signal transducer and activator of transcription 3 (STAT3) protein is critical for multiple cytokine and growth factor-induced biological responses in vivo. Its transcriptional activity is controlled by a transient phosphorylation of a critical tyrosine. Constitutive activation of STAT3 imparts resistance to apoptosis, promotes cell proliferation, and induces de novo micro-angiogenesis, three of the six cardinal hallmarks of a typical cancer cell. Earlier we reported the isolation of GRIM-19 as a growth suppressor using a genome-wide expression knockdown strategy. GRIM-19 binds to STAT3 and suppresses its transcriptional activity. To understand the pathological relevance of GRIM-19, we screened a set of primary head and neck tumors and identified three somatic mutations in GRIM-19. Wild-type GRIM-19 suppressed cellular transformation by a constitutively active form of STAT3, whereas tumor-derived mutants L71P, L91P and A95T significantly lost their ability to associate with STAT3, block gene expression, and suppress cellular transformation and tumor growth in vivo. Additionally, these mutants lost their capacity to prevent metastasis. These mutations define a mechanism by which STAT3 activity is deregulated in certain human head and neck tumors.
Respiratory polygraphy versus polysomnography for the diagnosis of obstructive sleep apnoeas in children

Full attended polysomnography (PSG) is the gold standard for diagnosis of obstructive sleep apnoeas (OSA). No consensus exists on the reliability of Respiratory Polygraphy (RP) for that purpose in children. This study aims to assess reliability between RP and PSG of determining sleep-related respiratory data in children. Twenty children with suspected OSA (10 yrs, 4-16) had full PSG performed in the Paediatric Sleep Centre, Robert Debre hospital, Paris, France. One investigator (LH) performed analysis using 2 modes in a random order: PSG mode (neurophysiologic and respiratory traces available) and RP mode (EEG, EOG, EMG not available on screen). Sleep was scored in PSG mode using Rechtschaffen-Kales criteria, and in RP mode using those of Moss et al (2005) which are mainly based upon variation of cardiac rhythm. Respiration was scored in the same manner for both modes using commonly accepted paediatric criteria. Intra-class correlation coefficients (ICC) were calculated. When using PSG mode, total sleep time was 517 min (360-633), obstructive apnoea-hypopnoea (OAH) index was 6.3 (0.2-66) and minimal SaO2 was 86% (71-95). Low ICC was found for sleep data. There was some reliability between RP and PSG of measuring OAH index and minimal SaO2, but not of measuring mean duration of events and sleep time in OAH. These results prompt further studies to be performed in a higher number of children before determining recommendations of routine use of RP in children with suspected OSA.
Fostering real-world clinical mental health research.

AIMS AND OBJECTIVES In this article, we identify key aspects for enhancing real-world research in mental health care clinical settings and broadly discuss some practicalities and issues that must be considered beforehand. BACKGROUND Practice which is evidence-based uses interventions or treatment methods that are supported by research findings for their quality and efficacy. Modern mental health settings endorse evidence-based practice and welcome the development of innovative, evidence-based approaches to care. Often, however, research findings are inaccessible, inconclusive, inconsistent, contradictory and overwhelming in sheer volume. Further, where there is no evidence, the absence of evidence is frequently mistaken for evidence of absence of the effectiveness of services. DESIGN Discursive paper. METHOD The main themes expressed in the literature were collated by the authors into themes, and their relevance to the development of real-world clinical mental health research is summarised with the aid of a vignette. CONCLUSIONS Ideally, research should be part of mainstream activities and as such constitute core business. Staff in mental health services should be encouraged to be research productive, and prospective clinical researchers should consider linking their studies to higher research degree programmes so that they can access resources, support and expertise to sustain motivation and morale. RELEVANCE TO CLINICAL PRACTICE For research findings to make the leap to evidence-based practice, the research needs to include real-world consumers and families typical of clinical practice supported by clinically relevant outcomes. Clinical and research leaders should create opportunities for academic and clinical nurses to collaborate in research, and researchers should ensure that clinically relevant outcomes are presented in ways that are meaningful and accessible to clinicians.
NANOPARTICLE AGGLOMERATES FOR PULMONARY DRUG DELIVERY

The Pulmonary route has been traditionally used to treat diseases of the respiratory tract. However, important research within the last two decades have shown that in addition to treating local diseases, a wide range of systemic diseases can be treated by delivering drugs to the lungs. The recent FDA approval to market Exubera®, an inhalable form of insulin developed by Pfizer, to treat Diabetes, may just be the stepping stone that the pharmaceutical industry needs to market other drugs to treat systemic diseases via the lungs. However, this technology still needs repeated drug doses to control glucose levels, as the inhaled drug is cleared rapidly. Technologies have been developed where inhaled particles are capable of controlled release of drug from the lungs. An important feature of these technologies is the large geometric size of the particles that makes it difficult for the lung macrophages to clear these particles, which results in longer residence times for the particles in the lungs. Owing to the porosity, these particles have lower densities making them deliverable to the deep lungs. However, no modulation of drug release can be achieved with these technologies when more drug release may be required. This additional requirement can only be assuaged by additional dosing of the drug formulation, which can have undesirable effects due to excess loading of excipients in the lungs. In an attempt to bring about modulation of release from long residence time particles, a novel concept was developed in our laboratory that has been termed as
The Mechanism by Which a Propeptide-encoded pH Sensor Regulates Spatiotemporal Activation of Furin*

Background: Histidine 69 in the propeptide is a pH sensor that mediates compartment-specific furin activation. Results: Histidine 69 protonation exposes the activation loop for proteolysis only within an optimal window for pH-dependent activation. Conclusion: A small structural change functions as the trigger that regulates precise spatiotemporal activation of furin. Significance: Our work provides insights into how individual proprotein convertases encode their unique compartment-specific activation. The proprotein convertase furin requires the pH gradient of the secretory pathway to regulate its multistep, compartment-specific autocatalytic activation. Although His-69 within the furin prodomain serves as the pH sensor that detects transport of the propeptide-enzyme complex to the trans-Golgi network, where it promotes cleavage and release of the inhibitory propeptide, a mechanistic understanding of how His-69 protonation mediates furin activation remains unclear. Here we employ biophysical, biochemical, and computational approaches to elucidate the mechanism underlying the pH-dependent activation of furin. Structural analyses and binding experiments comparing the wild-type furin propeptide with a nonprotonatable His-69 → Leu mutant that blocks furin activation in vivo revealed protonation of His-69 reduces both the thermodynamic stability of the propeptide as well as its affinity for furin at pH 6.0. Structural modeling combined with mathematical modeling and molecular dynamic simulations suggested that His-69 does not directly contribute to the propeptide-enzyme interface but, rather, triggers movement of a loop region in the propeptide that modulates access to the cleavage site and, thus, allows for the tight pH regulation of furin activation. Our work establishes a mechanism by which His-69 functions as a pH sensor that regulates compartment-specific furin activation and provides insights into how other convertases and proteases may regulate their precise spatiotemporal activation.
A systematic review of variability and reliability of manual and automated blood pressure readings.

AIMS AND OBJECTIVES To compare the accuracy and appropriateness of auscultatory (manual) and oscillometric (automated) devices for measuring blood pressure in clinical settings. BACKGROUND Accurate measurement of blood pressure is integral to early recognition of deterioration in the condition of a patient. Despite recommendations regarding the use of auscultatory devices in situations where treatment decisions are made dependent on blood readings, the use of automated machines is becoming common practice. DESIGN Systematic review. METHODS A search of the Medline, CINAHLPlus and The Cochrane Library databases was undertaken for papers published in English between January 1997-May 2009. Sixteen studies were identified that fulfilled the inclusion criteria. After quality assessment, all were included in the review. Results are presented in tabular and narrative form. RESULTS In 10 of the studies reviewed, the authors came to the conclusion that oscillometric devices were less accurate than auscultatory devices. However, in most cases the oscillometric device appears sufficiently accurate for clinical use, the exceptions being use with hypertensive patients, patients with arrhythmia and after trauma. Only two studies assessed the comparative accuracy of aneroid devices, and these indicated that they were more accurate than oscillometric devices, but the differences were not clinically important. CONCLUSIONS There are situations where the substitution of oscillometric for auscultatory devices could have particularly serious repercussions for the patient, such as when the patient is either hypertensive or hypotensive. However, further research is required on the use of aneroid sphygmomanometers as a replacement for mercury devices. RELEVANCE TO CLINICAL PRACTICE Practitioners should be made aware of the need to use auscultatory devices in specific circumstances, such as in management of hypertension, after the patient has experienced trauma or where there is significant potential for deterioration in the patient's condition.