Development of a novel computerised version of the Month Backwards Test: A comparison of performance in hospitalised elderly patients and final year medical students.

BACKGROUND AND AIMS: The Months Backwards Test (MBT) is a commonly used bedside test of cognitive function, but there is uncertainty as to optimal testing procedures. We examined performance among hospitalised elderly patients and cognitively intact young persons with verbal and computerised versions of the test. PARTICIPANTS AND METHODS: Fifty acute elderly medical inpatients and fifty final year medical students completed verbal (MBTv) and computerised (MBTc) versions of the MBT and the Montreal Cognitive Assessment (MoCA). Completion time and errors were compared. RESULTS: Thirty four participants scored <26 on the MoCA indicating significant cognitive impairment. The mean MoCA scores in the elderly medical group (23.6±3.4; range 13-28) were significantly lower than for the medical students (29.2±0.6; range 28-30: p<0.01). For the verbal months backwards test (MBTv), there were significantly more errors and longer completion times in the elderly medical patients (25.1±20.9 vs. 10.5±4.5; p<0.05). Completion times were 2-3 times longer for the MBTc compared to the MBTv (patients: 63.5±43.9 vs. students 20.3±4.4; p<0.05). There was high correlation between the two versions of the MBT (r=0.84) and also between the MBTc and the MoCA (r=0.85). The MBTc had higher correlation with visuospatial function (MBTc r=0.70, MBTv r=0.57). An MBTc cut-off time of 30s for distinguishing performance (pass/fail) had excellent sensitivity (100%) with modest specificity (44%) for cognitive impairment in elderly medical patients. CONCLUSION: The computerised MBT allows accurate and efficient testing of attention and general cognition in clinical populations.

Months backward test: A review of its use in clinical studies.

AIM: To review the use of the Months Backwards Test (MBT) in clinical and research contexts. METHODS: We conducted a systematic review of reports relating to the MBT based upon a search of PsychINFO and MEDLINE between January 1980 and December 2014. Only reports that specifically described findings pertaining to the MBT were included. Findings were considered in terms of rating procedures, testing performance, psychometric properties, neuropsychological studies and use in clinical populations. RESULTS: We identified 22 data reports. The MBT is administered and rated in a variety of ways with very little consistency across studies. It has been used to assess various cognitive functions including focused and sustained attention as well as central processing speed. Performance can be assessed in terms of the ability to accurately complete the test without errors ("MB accuracy"), and time taken to complete the test ("MB duration"). Completion time in cognitively intact subjects is usually < 20 s with upper limits of 60-90 s typically applied in studies. The majority of cognitively intact adults can complete the test without error such that any errors of omission are strongly suggestive of cognitive dysfunction. Coverage of clinical populations, including those with significant cognitive difficulties is high with the majority of subjects able to engage with MBT procedures. Performance correlates highly with other cognitive tests, especially of attention, including the digit span backwards, trailmaking test B, serial threes and sevens, tests of simple and complex choice reaction time, delayed story recall and standardized list learning measures. Test-retest and inter-rater reliability are high (both > 0.90). Functional magnetic resonance imaging studies comparing the months forward test and MBT indicate greater involvement of more complex networks (bilateral middle and inferior frontal gyri, the posterior parietal cortex and the left anterior cingulate gyrus) for backwards cognitive processing. The MBT has been usefully applied to the study of a variety of clinical presentations, for both cognitive and functional assessment. In addition to the assessment of major neuropsychiatric conditions such as delirium, dementia and Mild Cognitive Impairment, the MBT has been used in the assessment of concussion, profiling of neurocognitive impairments in organic brain disorders and Parkinson's disease, prediction of delirium risk in surgical patients and medication compliance in diabetes. The reported sensitivity for acute neurocognitive disturbance/delirium in hospitalised patients is estimated at 83%-93%. Repeated testing can be used to identify deteriorating cognitive function over time. CONCLUSION: The MBT is a simple, versatile tool that is sensitive to significant cognitive impairment. Performance can be assessed according to accuracy and speed of performance. However, greater consistency in administration and rating is needed. We suggest two approaches to assessing performance - a simple (pass/fail) method as well as a ten point scale for rating test performance (467).

Air quality implications of the Deepwater Horizon oil spill.

During the Deepwater Horizon (DWH) oil spill, a wide range of gas and aerosol species were measured from an aircraft around, downwind, and away from the DWH site. Additional hydrocarbon measurements were made from ships in the vicinity. Aerosol particles of respirable sizes were on occasions a significant air quality issue for populated areas along the Gulf Coast. Yields of organic aerosol particles and emission factors for other atmospheric pollutants were derived for the sources from the spill, recovery, and cleanup efforts. Evaporation and subsequent secondary chemistry produced organic particulate matter with a mass yield of 8 ± 4% of the oil mixture reaching the water surface. Approximately 4% by mass of oil burned on the surface was emitted as soot particles. These yields can be used to estimate the effects on air quality for similar events as well as for this spill at other times without these data. Whereas emission of soot from burning surface oil was large during the episodic burns, the mass flux of secondary organic aerosol to the atmosphere was substantially larger overall. We use a regional air quality model to show that some observed enhancements in organic aerosol concentration along the Gulf Coast were likely due to the DWH spill. In the presence of evaporating hydrocarbons from the oil, NO(x) emissions from the recovery and cleanup operations produced ozone.

Biocorrosion and uptake of titanium by human osteoclasts.

All metals in contact with a biological system undergo corrosion through an electrochemical redox reaction. This study investigated whether human osteoclasts (OC) are able to grow on titanium and aluminum, and directly corrode the metals leading to the release of corresponding metal ions, which are believed to cause inflammatory reactions and activate osteoclastic differentiation. Scanning electron microscopy analysis demonstrated long-term viable OC cultures on the surface of titanium and aluminum foils. Atomic emission spectrometry investigations showed significantly increased levels of aluminum in the supernatant of OC cultured on aluminum; however, all measurements in the supernatants of cell cultures on titanium were below detection limits. Despite this, confocal microscopy analysis with Newport Green DCF diacetate ester staining depicted intense fluorescence throughout the cytoplasm and nucleolus of OC cultured on titanium foils. Comparable fluorescence intensities were not observed in monocytes and control cells cultured on glass. The present study demonstrated that human osteoclast precursors are able to grow and differentiate toward mature OC on titanium and aluminum. Furthermore, it established that the mature cells are able to directly corrode the metal surface and take up corresponding metal ions, which subsequently may be released and thereby induce the formation of osteolytic lesions in the periprosthetic bone, contributing to the loosening of the implant.

Uptake and intracellular distribution of various metal ions in human monocyte-derived dendritic cells detected by Newport Green DCF diacetate ester.

BACKGROUND: The attempt to visualise intracellular protein metal complexes has currently been difficult due to the unavailability of probes for such molecular structures. Newport Green DCF diacetate ester is a cell permeant acetate ester, which becomes fluorescent after hydrolysis. This molecule is initially uncharged, allowing it to pass through cell membranes. Once in the cell, it is hydrolysed and becomes charged, hindering its escape from the cell and allowing it to bind charged protein metal complexes, which then become fluorescent. METHODS: In this study, we exposed cultured human monocyte-derived dendritic cells (mDC) to a variety of metal ions with the aim of having the cells take up and process protein metal complexes. Newport Green DCF diacetate ester was used to fluorescently label intracellular protein metal complexes. RESULTS: Flow cytometry analysis and confocal imaging showed specific staining for mDC exposed to aluminium, chromium, nickel, titanium and zirconium ions. The intensity of staining varied between ion types, whereby Ti(III) resulted in the brightest fluorescence signal. Aluminium, Cr(III), Ni, Ti(IV) and Zr(IV) were also clearly detectable. CONCLUSION: For the first time, intracellular metal ion protein complexes undergoing cellular processing were successfully visualised in human mDC using flow cytometry and confocal microscopy.

Titanium IV ions induced human osteoclast differentiation and enhanced bone resorption in vitro.

There is increasing evidence that titanium (Ti) ions are released from orthopedic implants, with concentrations in the range of 1 microM in tissue and blood, and may play a role in aseptic loosening of orthopedic implants. This study investigated whether Ti(IV) ions induce differentiation of monocytic osteoclast precursors into osteo-resorptive multinucleated cells and influence the activation and function of in vitro generated osteoclasts. Human monocytes and in vitro generated osteoclasts were exposed to 1 microM Ti(IV) ions for 10 days. Thereafter, osteoclast differentiation, activation, and function were evaluated. Transcription of specific osteoclastic genes was measured using quantitative reverse transcription polymerase chain reactions, which showed increased expression of tartrate-resistant acid phosphatase (TRAP) in approximately 20% of Ti(IV)-treated monocytes. Detection and quantification of intracellular TRAP activity using ELF97 as a fluorescent substrate revealed a significant increase of TRAP-positive cells in Ti(IV)-treated monocytes. Additionally, as demonstrated on dentin slide cultures, Ti(IV)-treated monocytes became functional bone resorbing cells, significantly increasing their osteo-resorptive activity to similar levels as osteoclasts in vitro. These results suggest that Ti(IV) ions released by biocorrosion from orthopedic implants induce differentiation of monocytes toward mature, functional osteoclasts, which may well contribute the pathomechanism of aseptic loosening.

Functional dissociation of the basolateral transcytotic compartment from the apical phago-lysosomal compartment in human osteoclasts.

Tartrate-resistant acid phosphatase (TRAP) is essential for elimination of Staphylococcus aureus, the main infectious agent responsible for osteomyelitis. This in vitro study investigated uptake and processing of fluorescence-labeled S. aureus by human osteoclasts and dendritic cells. The cells were stained for TRAP and the acidic compartment using a fluorescence-based protocol. In dendritic cells, TRAP and bacteria were colocalized. In osteoclasts, there was no colocalization of bacteria, TRAP, or the acidic compartment, indicating that there are three distinct vesicular compartments: the apical phago-lysosomal compartment, the basal secretory compartment, and the basolateral transcytotic compartment. Dissociation of the TRAP-containing transcytotic vesicles from the apical phago-lysosomal compartment may restrain osteoclasts from eliminating S. aureus.

Historic PM2.5/PM10 Concentrations in the Southeastern United States-Potential Implications of the Revised Particulate Matter Standard.

This report summarizes a PM2.5/PM10 particulate matter data set consisting of 861 PM2.5/PM10 sample pairs collected with dichotomous samplers by the Tennessee Valley Authority (TVA) from 1982 to 1991. Eight monitoring stations, ranging from urban-industrial to rural-background, were operated across three east-central U.S. states. Annual average PM2.5 concentrations ranged from 12.6 to 21.3 micrograms per cubic meter (µg/m3), with an overall mean of 15.7 µg/m3. Likewise, annual average PM10 concentrations ranged from 17.8 to 33.7 µg/m3, with an overall mean of 23.7 µg/m3. High summer-low winter seasonality was evident, particularly for PM2.5, with the highest monthly PM2.5 and PM10 concentrations in August (26.4 and 37.5 µg/m3, respectively) and the lowest in February (9.9 and 15.3 µg/m3, respectively). A strong association (r2 = 0.84) was found between PM and PM mass with PM mass contributing, on average, 67% of PM10 mass. Applying TVA's PM2 5/PM10 ratio to recent (1993-1995) regional high-volume PM10 Aerometric Information Retrieval System (AIRS) data for the east-central United States suggests that as many as 80% of monitored counties would have equaled or exceeded the level of the new annual PM2.5 metric of 15 µg/m3. A decline in average PM2.5 mass on the order of 3-5 µg/m3 from 1982 through 1991 is also suggested. Daily PM2 5 mass appears to be reasonably well associated (r = 0.47) with maximum hourly ozone during the warmer months (spring through fall). Sulfate compounds comprise a major portion of the measured PM2 5 mass, with that fraction being highest in the summer months. Viewed collectively, these data suggest that although compliance with the annual and 24-hr PM and 24-hr PM metrics should prove readily attainable, the annual PM2.5 metric will present a major regulatory management challenge for much of the east-central United States.