Survey of the extracellular matrix architecture across the rat arterial tree.

OBJECTIVE: To understand arterial remodeling and the pathophysiology of arterial diseases, it is necessary to understand the baseline qualities and variations in arterial structure. Arteries could differ in wall thickness, laminar structure, and laminar fenestration depending on their position within the arterial tree. We endeavored to evaluate and compare the extracellular matrix structure of different arteries throughout the arterial tree, from the aorta to the adductor muscle arteriole, with a particular focus on the internal elastic lamina (IEL). METHODS: Arterial segments were harvested from male Sprague-Dawley rats and imaged using multiple modalities. En face scans by multiphoton microscopy were used to compare native-state adventitial collagen undulation and IEL fenestration. RESULTS: Collagen undulation was similar across most examined arteries but straighter in the skeletal muscle arterioles (P < .05). The elastic lamellae showed several differences. The IEL fenestrae were similar in average size among abdominal aorta and celiac, renal, common iliac, and common femoral arteries (range, 14-24 µm2), with wide within-vessel variance (square of the standard deviation, 462-1904 µm4). However, they tended to be smaller (9.08 µm2) and less variable (square of the standard deviation, 88.3 µm4) in the popliteal artery. Fenestrae were greater in number in the superior mesenteric artery (SMA; 6686/mm2; P < .05) and profunda femoris artery (PFA; 11,042/mm2; P < .05) compared with the other examined vessels, which ranged in surface density from 3143/mm2 to 4362/mm2. The SMA and PFA also showed greater total fenestration as a proportion of the IEL surface area (SMA, 15.04%; P < .05; PFA, 24.11%; P < .001) than the other examined arteries (range of means, 4.7%-9.4%). The arteriolar IEL was structurally distinct, comparable to a low-density wireframe. Other structural differences were also noted, including differences in the number of medial lamellae along the arterial tree. CONCLUSIONS: We found that vessels at different locations along the arterial tree differ in structure. The SMA, PFA, and intramuscular arterioles have fundamental differences in the extracellular matrix structure compared with other arteries. Location-specific features such as the medial lamellae number and elastic laminar structure might have relevance to physiology and confer vulnerabilities to the development of pathology.

Measuring therapeutic engagement in acute mental health inpatient environments: the perspectives of service users and mental health nurses.

BACKGROUND: A key component of caring for service users (SUs) in acute mental health inpatient environments is Therapeutic Engagement (TE). To that end, the Therapeutic Engagement Questionnaire (TEQ) was developed and validated. The TEQ measures TE between SUs and registered mental health nurses (RMHNs) from the perspective of both parties and can quantify and recognise how nurses engage with SUs and monitor this activity as well as its enhancement of SU care and recovery. The aim of this study was to explore the views of SUs and RMHNs in relation to the TEQ and how it could be adopted into clinical practice within an acute inpatient environment. METHODS: As part of the validation stage of the development of the TEQ, the views of 628 SUs and 543 RMHNs were collected using a qualitative approach by way of free text at the end of the questionnaire. Two questions required free text response: - 'what do you think of the TEQ?', and 'how can it be utilised?' RESULTS: Following thematic analysis, it was found that both sets of participants stated that such a tool could be utilised to improve the service, could help nurses with reflective practice, be utilised as part of clinical supervision and to aid nurses' professional development. The nurse participants also stated that such a tool would help track SU participation and enablement in their care. Furthermore, the nurses noted that the tool would help to reinforce the core 'caring' value of nursing and the overall goal of recovery. The SUs added that the TEQ would recognise the work of mental health nurses and provide them with a clear opportunity to express their views in relation to nursing staff. CONCLUSIONS: Therapeutic engagement (TE) has been identified as part of the repertoire of mental health nursing and both groups of participants identified how a tool to assess this construct may be utilised in day-to-day clinical practice to the benefit of each group.

Mild Traumatic Brain Injury Chronically Impairs Sleep- and Wake-Dependent Emotional Processing.

Study Objectives: A single traumatic brain injury (TBI), even when mild (ie, concussion), can cause lasting consequences. Individuals with a history of chronic (>1-year prior) mild TBI have an increased risk of mood disturbances (eg, depression, suicide). This population also has lingering sleep alterations, including poor sleep quality and changes in sleep stage proportions. Given these sleep deficits, we aimed to test whether sleep-dependent emotional memory consolidation is reduced in this population. We utilized a mild TBI group (3.7 ± 2.9 years post injury) and an uninjured (non-TBI) population. Methods: Participants viewed negative and neutral images both before and after a 12-hour period containing sleep ("Sleep" group) or an equivalent period of time spent awake ("Wake" group). Participants rated images for valence/arousal at both sessions, and memory recognition was tested at session two. Results: The TBI group had less rapid eye movement (REM), longer REM latency, and more sleep complaints. Sleep-dependent memory consolidation of nonemotional images was present in all participants. However, consolidation of negative images was only present in the non-TBI group. A lack of differentiation between the TBI Sleep and Wake groups was due to poor performance in the sleep group and, unexpectedly, enhanced performance in the wake group. Additionally, although the non-TBI participants habituated to negative images over a waking period, the TBI participants did not. Conclusions: We propose disrupted sleep- and wake-dependent emotional processing contributes to poor emotional outcomes following chronic, mild TBI. This work has broad implications, as roughly one-third of the US population will sustain a mild TBI during their lifetime.

Bipartite recognition of target RNAs activates DNA cleavage by the Type III-B CRISPR-Cas system.

CRISPR-Cas systems eliminate nucleic acid invaders in bacteria and archaea. The effector complex of the Type III-B Cmr system cleaves invader RNAs recognized by the CRISPR RNA (crRNA ) of the complex. Here we show that invader RNAs also activate the Cmr complex to cleave DNA. As has been observed for other Type III systems, Cmr eliminates plasmid invaders in Pyrococcus furiosus by a mechanism that depends on transcription of the crRNA target sequence within the plasmid. Notably, we found that the target RNA per se induces DNA cleavage by the Cmr complex in vitro. DNA cleavage activity does not depend on cleavage of the target RNA but notably does require the presence of a short sequence adjacent to the target sequence within the activating target RNA (rPAM [RNA protospacer-adjacent motif]). The activated complex does not require a target sequence (or a PAM) in the DNA substrate. Plasmid elimination by the P. furiosus Cmr system also does not require the Csx1 (CRISPR-associated Rossman fold [CARF] superfamily) protein. Plasmid silencing depends on the HD nuclease and Palm domains of the Cmr2 (Cas10 superfamily) protein. The results establish the Cmr complex as a novel DNA nuclease activated by invader RNAs containing a crRNA target sequence and a rPAM.

The CRISPR-associated Csx1 protein of Pyrococcus furiosus is an adenosine-specific endoribonuclease.

Prokaryotes are frequently exposed to potentially harmful invasive nucleic acids from phages, plasmids, and transposons. One method of defense is the CRISPR-Cas adaptive immune system. Diverse CRISPR-Cas systems form distinct ribonucleoprotein effector complexes that target and cleave invasive nucleic acids to provide immunity. The Type III-B Cmr effector complex has been found to target the RNA and DNA of the invader in the various bacterial and archaeal organisms where it has been characterized. Interestingly, the gene encoding the Csx1 protein is frequently located in close proximity to the Cmr1-6 genes in many genomes, implicating a role for Csx1 in Cmr function. However, evidence suggests that Csx1 is not a stably associated component of the Cmr effector complex, but is necessary for DNA silencing by the Cmr system in Sulfolobus islandicus. To investigate the function of the Csx1 protein, we characterized the activity of recombinant Pyrococcus furiosus Csx1 against various nucleic acid substrates. We show that Csx1 is a metal-independent, endoribonuclease that acts selectively on single-stranded RNA and cleaves specifically after adenosines. The RNA cleavage activity of Csx1 is dependent upon a conserved HEPN motif located within the C-terminal domain of the protein. This motif is also key for activity in other known ribonucleases. Collectively, the findings indicate that invader silencing by Type III-B CRISPR-Cas systems relies both on RNA and DNA nuclease activities from the Cmr effector complex as well as on the affiliated, trans-acting Csx1 endoribonuclease.

The association between personality disorder and an act of deliberate self harm in the older person.

BACKGROUND: Suicide rates are higher in the over 65s than in younger adults and there is a strong link between deliberate self harm (DSH) and suicide in older people. The association between personality disorder (PD) and DSH in older adults remains uncertain. Our objective was to describe this association. METHODS: A case control study was conducted in which participants were: (i) those who had undertaken an act of DSH and (ii) a hospital-based control group drawn from a geographical contiguous population. PD was assessed using the Standardised Assessment of Personality (SAP). RESULTS: Seventy-seven cases of DSH were identified; 61 (79.2%) of these participants were interviewed. There were 171 potential controls identified of whom 140 (81.9%) were included. An SAP was completed in 45/61 (73.8%) of cases and 100/140 (71.4%) of controls. The mean age was 79.8 years (SD = 9, range 65-103). The crude odds ratio for the association between PD and DSH was 5.91 [(95% CI 2.3, 14.9) p<0.0001]. There was a strong interaction with age stratified at 80 years. There was no association between PD and DSH after age 80. The adjusted odds ratio for PD in the group <80 years was 20.5 [(95% CI 3, 141) p = 0.002]. Borderline and impulsive PD traits tended to be associated with an episode of DSH more than other personality types. CONCLUSIONS: PD appears to be a strong and independent risk for an act of DSH in people aged between 65 and 80 years and should be looked for as part of any risk assessment in this population. Access to specialist services may be required to optimally manage this problem and reduce the subsequent risk of suicide.

Apportionment of ambient primary and secondary fine particulate matter at the Pittsburgh National Energy Laboratory particulate matter characterization site using positive matrix factorization and a potential source contributions function analysis.

Fine particulate matter (PM2.5) concentrations associated with 202 24-hr samples collected at the National Energy Technology Laboratory (NETL) particulate matter (PM) characterization site in south Pittsburgh from October 1999 through September 2001 were used to apportion PM2.5 into primary and secondary contributions using Positive Matrix Factorization (PMF2). Input included the concentrations of PM2.5 mass determined with a Federal Reference Method (FRM) sampler, semi-volatile PM2.5 organic material, elemental carbon (EC), and trace element components of PM2.5. A total of 11 factors were identified. The results of potential source contributions function (PSCF) analysis using PMF2 factors and HYSPLIT-calculated back-trajectories were used to identify those factors associated with specific meteorological transport conditions. The 11 factors were identified as being associated with emissions from various specific regions and facilities including crustal material, gasoline combustion, diesel combustion, and three nearby sources high in trace metals. Three sources associated with transport from coal-fired power plants to the southeast, a combination of point sources to the northwest, and a steel mill and associated sources to the west were identified. In addition, two secondary-material-dominated sources were identified, one was associated with secondary products of local emissions and one was dominated by secondary ammonium sulfate transported to the NETL site from the west and southwest. Of these 11 factors, the four largest contributors to PM2.5 were the secondary transported material (dominated by ammonium sulfate) (47%), local secondary material (19%), diesel combustion emissions (10%), and gasoline combustion emissions (8%). The other seven factors accounted for the remaining 16% of the PM2.5 mass. The findings are consistent with the major source of PM2.5 in the Pittsburgh area being dominated by ammonium sulfate from distant transport and so decoupled from local activity emitting organic pollutants in the metropolitan area. In contrast, the major local secondary sources are dominated by organic material.

Apportionment of ambient primary and secondary fine particulate matter during a 2001 summer intensive study at the CMU Supersite and NETL Pittsburgh site.

Gaseous and particulate pollutant concentrations associated with five samples per day collected during a July 2001 summer intensive study at the Pittsburgh Carnegie Mellon University (CMU) Supersite were used to apportion fine particulate matter (PM2.5) into primary and secondary contributions using PMF2. Input to the PMF2 analysis included the concentrations of PM2.5 nonvolatile and semivolatile organic material, elemental carbon (EC), ammonium sulfate, trace element components, gas-phase organic material, and NO(x), NO2, and O3 concentrations. A total of 10 factors were identified. These factors are associated with emissions from various sources and facilities including crustal material, gasoline combustion, diesel combustion, and three nearby sources high in trace metals. In addition, four secondary sources were identified, three of which were associated with secondary products of local emissions and were dominated by organic material and one of which was dominated by secondary ammonium sulfate transported to the CMU site from the west and southwest. The three largest contributors to PM2.5 were secondary transported material (dominated by ammonium sulfate) from the west and southwest (49%), secondary material formed during midday photochemical processes (24%), and gasoline combustion emissions (11%). The other seven sources accounted for the remaining 16% of the PM2.5. Results obtained at the CMU site were comparable to results previously reported at the National Energy Technology Laboratory (NETL), located approximately 18 km south of downtown Pittsburgh. The major contributor at both sites was material transported from the west and southwest. Some difference in nearby sources could be attributed to meteorology as evaluated by HYSPLIT model back-trajectory calculations. These findings are consistent with the majority of the secondary ammonium sulfate in the Pittsburgh area being the result of contributions from distant transport, and thus decoupled from local activity involving organic pollutants in the metropolitan area. In contrast, the major local secondary sources were dominated by organic material.

Quantitative characterizations of speech rhythm: syllable-timing in Singapore English.

British English and Singapore English are said to differ in rhythmic patterning. British English is commonly described as stress-timed, but Singapore English is claimed to be syllable-timed. In the present paper, we explore the acoustic nature of the suggested cross-varietal difference. In directly comparable samples from British English and Singapore English, two types of acoustic measurements were taken; we calculated a variability index reflecting changes in vowel length over utterances, and measurements reflecting vowel quality. Our findings provide acoustic data which support the hypothesized cross-varietal difference in rhythmic patterning; we show (1) that successive vowel durations are more nearly equal in Singapore English than in British English, and (2) that reduced vowels pattern more peripherally in the F1/F2 formant space in Singapore English than in British English. We complete the paper with a comparison of our vowel variability index with a set of acoustic measures for rhythm proposed by Ramus, Nespor, and Mehler (1999), which focus on variability in vocalic and intervocalic intervals. We conclude that our variability index is more successful in capturing rhythmic differences than Ramus et al. (1999)'s measures, and that an application of our index to Ramus et al.'s intervocalic measure may provide a further diagnostic of rhythmic class.

Categorising [s], [integral of] and intermediate electropalatographic patterns: neural networks and other approaches.

We consider two approaches to the interpretation of EPG data, using materials designed for the investigation of [s]-[integral of] assimilations across word boundaries, as in boss Shep. A contact index is based on electrode contact in different row groups, whereas a neural network is used to determine patterns of contact. Both approaches are speaker sensitive, reflecting the wide variation in [s] and [integral of] articulation between speakers. The advantage of the neural net analysis is that the investigator need not make any assumptions about the relative value of specific electrodes or groups of electrodes. We found that the 'hand-selected' index, in general, modelled linguopalatal movement for all degrees of [s]-[integral of] assimilation better than the neural net. However, the neural net very successfully characterised stable /s/ and /integral of/ and has the potential to give an accurate representation of intermediate assimilatory cases, if trained on a more varied input set than the rather limited one used in this experiment.

Medicolegal documentation of prehospital triage.

Patients evaluated by paramedics but not transported to the hospital account for 50% to 90% of emergency medical services lawsuits. We reviewed 2,698 consecutive paramedic run reports to examine documentation in these cases. Documentation criteria for prehospital patient release were history, physical examination, vital signs, mental status, lack of significant mental impairment, and for patients refusing care, that risks of refusing were understood. Criteria for appropriate release were met in 65.2% of cases. Criteria omitted in inappropriate releases were risks of refusing care in 481 (51.3% of inappropriate releases), vitals in 320 (34.1%), mental status in 188 (20.0%), lack of impairment in 120 (12.8%), and history or physical in 19 (2.0%) cases. Age from 0 to 14 and 65 or more years and prehospital assessment of hyperventilation, psychiatric emergency, choking, infection, and patient deceased were significantly associated with appropriate release. Age from 35 to 54 years and prehospital diagnosis of no injury, head injury, seizure, minor trauma, and ethanol use were significantly associated with inappropriate releases. There was no association of appropriate release or inappropriate release with patient sex, contact with medical control, length of encounter, or time of day. Only one patient complication was believed due to inappropriate triage; this could be improved by implementation of standardized criteria.

Digital angiography in the pediatric patient with congenital heart disease: comparison with standard methods.

Digital subtraction angiography (DSA) permits high-resolution cardiac imaging with relatively low doses of contrast medium and reduced radiation exposure. These are potential advantages in children with congenital heart disease. Computer-based DSA (30 frames/sec) and conventional cutfilm angiography (6 frames/sec) or cineangiography (60 frames/sec) were compared in 42 patients, ages 2 months to 18 years (mean 7.8 years) and weighing 3.4 to 78.5 kg (mean 28.2 kg). There were 29 diagnoses that included valvular regurgitant lesions, obstructive lesions, various shunt abnormalities, and a group of miscellaneous anomalies. For injections made at a site distant from the lesion and on the right side of the circulation, the mean dose of contrast medium was 60% to 100% of the conventional dose given during standard angiography. With injections made close to the lesion and on the left side of the circulation, the mean dose of contrast medium was 27.5% to 42% of the conventional dose. Radiation exposure for each technique was markedly reduced in all age groups. A total of 92 digital subtraction angiograms were performed. Five studies were suboptimal because too little contrast medium was injected; in the remaining 87 injections, DSA and conventional studies resulted in identical diagnoses in 81 instances (p less than .001 vs chance). The remaining six injections made during DSA failed to confirm diagnoses made angiographically by standard cutfilm angiography or cineangiography. We conclude that DSA usually provides diagnostic information equivalent to that available from cutfilm angiography and cineangiography, but DSA requires considerably lower doses of contrast medium and less radiation exposure than standard conventional methods.

Non-group D streptococcal meningitis misidentified as enterococcal meningitis. Diagnostic and therapeutic implications of misdiagnosis by screening microbiology.

Two patients had nonhemolytic Gram-positive coccal meningitis. Both pathogens were initially misidentified as a group D enterococcus by growth in "selective" media, which led to the use of inappropriate and potentially toxic systemic and intrathecal aminoglycosides. Careful evaluation of the antibiotic sensitivity data and additional microbiological studies allowed correct identification of the organism. The important diagnostic and therapeutic considerations in differentiating true enterococcal infections, especially meningitis, from those caused by other alpha-hemolytic or nonhemolytic streptococci are emphasized. A simple laboratory schema for rapid recognition of such pathogens is reviewed.