Lower back pain (LBP) occurs in 80% of adults in their lifetime; resulting in LBP being one of the biggest causes of disability worldwide. Chronic LBP has been linked to the degeneration of the ...intervertebral disc (IVD). The current treatments for chronic back pain only provide alleviation of symptoms through pain relief, tissue removal, or spinal fusion; none of which target regenerating the degenerate IVD. As nucleus pulposus (NP) degeneration is thought to represent a key initiation site of IVD degeneration, cell therapy that specifically targets the restoration of the NP has been reviewed here. A literature search to quantitatively assess all cell types used in NP regeneration was undertaken. With key cell sources: NP cells; annulus fibrosus cells; notochordal cells; chondrocytes; bone marrow mesenchymal stromal cells; adipose‐derived stromal cells; and induced pluripotent stem cells extensively analyzed for their regenerative potential of the NP. This review highlights: accessibility; expansion capability in vitro; cell survival in an IVD environment; regenerative potential; and safety for these key potential cell sources. In conclusion, while several potential cell sources have been proposed, iPSC may provide the most promising regenerative potential.
Cell sources and lineages proposed for regeneration of the intervertebral disc. This review highlights: accessibility; expansion capability in vitro; cell survival in an IVD environment; regenerative potential; and safety for these key potential cell sources. In conclusion, while several potential cell sources have been proposed, induced pluripotent stem cells may provide the most promising regenerative potential.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Multiphoton microscopy (MPM) has found a niche in the world of biological imaging as the best noninvasive means of fluorescence microscopy in tissue explants and living animals. Coupled with ...transgenic mouse models of disease and 'smart' genetically encoded fluorescent indicators, its use is now increasing exponentially. Properly applied, it is capable of measuring calcium transients 500 microm deep in a mouse brain, or quantifying blood flow by imaging shadows of blood cells as they race through capillaries. With the multitude of possibilities afforded by variations of nonlinear optics and localized photochemistry, it is possible to image collagen fibrils directly within tissue through nonlinear scattering, or release caged compounds in sub-femtoliter volumes.
In deserts, the interplay between occasional fluvial events and persistent aeolian erosion can form composite modern and relict surfaces, especially on the distal portion of alluvial fans. There, ...relief inversion of alluvial deposits by differential erosion can form longitudinal ridges. We identified two distinct ridge types formed by relief inversion on converging alluvial fans in the hyperarid Chilean Atacama Desert. Although they are co-located and similar in scale, the ridge types have different ages and formation histories that apparently correspond to minor paleoclimate variations. Gravel-armored ridges are remnants of deflated alluvial deposits with a bimodal sediment distribution (gravel and sand) dated to a minor pluvial phase at the end of the Late Pleistocene (~12 kyr). In contrast, younger (~9 kyr) sulfate-capped ridges formed during a minor arid phase with evaporite deposition in a pre-existing channel that armored the underlying deposits. Collectively, inverted channels at Salar de Llamara resulted from multiple episodes of surface overland flow and standing water spanning several thousand years. Based on ridge relief and age, the minimum long-term deflation rate is 0.1–0.2 m/kyr, driven primarily by wind erosion. This case study is an example of the equifinality concept whereby different processes lead to similar landforms. The complex history of the two ridge types can only be generally constrained in remotely sensed data. In situ observations are required to discern the specifics of the aqueous history, including the flow type, magnitude, sequence, and paleoenvironment. These findings have relevance for interpreting similar landforms on Mars.
•Two inverted channel types co-located on a bajada have different histories.•Wind erosion of gravel-bearing mudflows formed a clast-armored inverted channel.•Evaporites deposited in pre-existing channels were eroded to sulfate-capped ridges.•Key events that led to relief inversion may link to minor paleoclimate variations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose
Mild cognitive impairment (MCI) can be the prodromal phase of Alzheimer's disease (AD) where appropriate intervention might prevent or delay conversion to AD. Given this, there has been ...increasing interest in using magnetic resonance imaging (MRI) and neuropsychological testing to predict conversion from MCI to AD. Recent evidence suggests that the choroid plexus (ChP), neural substrates implicated in brain clearance, undergo volumetric changes in MCI and AD. Whether the ChP is involved in memory changes observed in MCI and can be used to predict conversion from MCI to AD has not been explored.
Method
The current study used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to investigate whether later progression from MCI to AD (progressive MCI pMCI, n = 115) or stable MCI (sMCI, n = 338) was associated with memory scores using the Rey Auditory Verbal Learning Test (RAVLT) and ChP volumes as calculated from MRI. Classification analyses identifying pMCI or sMCI group membership were performed to compare the predictive ability of the RAVLT and ChP volumes.
Finding
The results indicated a significant difference between pMCI and sMCI groups for right ChP volume, with the pMCI group showing significantly larger right ChP volume (p = .01, 95% confidence interval −.116, −.015). A significant linear relationship between the RAVLT scores and right ChP volume was found across all participants, but not for the two groups separately. Classification analyses showed that a combination of left ChP volume and auditory verbal learning scores resulted in the most accurate classification performance, with group membership accurately predicted for 72% of the testing data.
Conclusion
These results suggest that volumetric ChP changes appear to occur before the onset of AD and might provide value in predicting conversion from MCI to AD.
Choroid plexus (ChP) volumes and Rey Auditory Verbal Learning Test—Immediate (RAVLT‐I) scores were compared between participants who later progressed from MCI to Alzheimer's disease (pMCI) and those who remained stable (sMCI). The right ChP was larger in the pMCI group, and the left ChP and RAVLT‐I were the best‐performing classifiers for predicting group membership.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
This study examined the extent to which delivery of the minimal Smoke-Free Homes intervention by trained 2-1-1 information and referral specialists had an effect on the adoption of home smoking bans ...in low-income households. A randomized controlled trial was conducted among 2-1-1 callers (n = 500) assigned to control or intervention conditions. 2-1-1 information and referral specialists collected baseline data and delivered the intervention consisting of 3 mailings and 1 coaching call; university-based data collectors conducted follow-up interviews at 3 and 6 months post-baseline. Data were collected from June 2013 through July 2014. Participants were mostly female (87.2%), African American (61.4%), and smokers (76.6%). Participants assigned to the intervention condition were more likely than controls to report a full ban on smoking in the home at both 3- (38.1% vs 19.3%, p = < .001) and 6-month follow-up (43.2% vs 33.2%, p = .02). The longitudinal intent-to-treat analysis showed a significant intervention effect over time (OR = 1.31, p = .001), i.e. OR = 1.72 at 6 months. This study replicates prior findings showing the effectiveness of the minimal intervention to promote smoke-free homes in low-income households, and extends those findings by demonstrating they can be achieved when 2-1-1 information and referral specialists deliver the intervention. Findings offer support for this intervention as a generalizable and scalable model for reducing secondhand smoke exposure in homes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ObjectiveTo assess how easily minors can purchase cigarettes online and online cigarette vendors’ compliance with federal age/ID verification and shipping regulations, North Carolina's 2013 tobacco ...age verification law, and federal prohibitions on the sale of non-menthol flavoured cigarettes or those labelled or advertised as ‘light’.MethodsIn early 2014, 10 minors aged 14–17 attempted to purchase cigarettes by credit card and electronic check from 68 popular internet vendors.ResultsMinors received cigarettes from 32.4% of purchase attempts, all delivered by the US Postal Service (USPS) from overseas sellers. None failed due to age/ID verification. All failures were due to payment processing problems. USPS left 63.6% of delivered orders at the door with the remainder handed to minors with no age verification. 70.6% of vendors advertised light cigarettes and 60.3% flavoured, with 23.5% and 11.8%, respectively, delivered to the teens. Study credit cards were exposed to an estimated $7000 of fraudulent charges.ConclusionsDespite years of regulations restricting internet cigarette sales, poor vendor compliance and lack of shipper and federal enforcement leaves minors still able to obtain cigarettes (including ‘light’ and flavoured) online. The internet cigarette marketplace has shifted overseas, exposing buyers to widespread credit card fraud. Federal agencies should rigorously enforce existing internet cigarette sales laws to prevent illegal shipments from reaching US consumers, shut down non-compliant and fraudulent websites, and stop the theft and fraudulent use of credit card information provided online. Future studies should assess whether these agencies begin adequately enforcing the existing laws.
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CEKLJ, CMK, NUK, UL, UM, UPUK
The coronavirus disease 2019 pandemic has had an impact on healthcare systems around the world with 3 million people contracting the disease and 208,000 cases resulting in death as of this writing. ...Information regarding coronavirus infection in pregnancy is still limited.
This study aimed to describe the clinical course of severe and critical coronavirus disease 2019 in hospitalized pregnant women with positive laboratory testing for severe acute respiratory syndrome coronavirus 2.
This is a cohort study of pregnant women with severe or critical coronavirus disease 2019 hospitalized at 12 US institutions between March 5, 2020, and April 20, 2020. Severe disease was defined according to published criteria as patient-reported dyspnea, respiratory rate >30 per minute, blood oxygen saturation ≤93% on room air, ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen <300 mm Hg, or lung infiltrates >50% within 24–48 hours on chest imaging. Critical disease was defined as respiratory failure, septic shock, or multiple organ dysfunction or failure. Women were excluded from the study if they had presumed coronavirus disease 2019, but laboratory testing was negative. The primary outcome was median duration from hospital admission to discharge. Secondary outcomes included need for supplemental oxygen, intubation, cardiomyopathy, cardiac arrest, death, and timing of delivery. The clinical courses are described by the median disease day on which these outcomes occurred after the onset of symptoms. Treatment and neonatal outcomes are also reported.
Of 64 hospitalized pregnant women with coronavirus disease 2019, 44 (69%) had severe disease, and 20 (31%) had critical disease. The following preexisting comorbidities were observed: 25% had a pulmonary condition, 17% had cardiac disease, and the mean body mass index was 34 kg/m2. Gestational age was at a mean of 29±6 weeks at symptom onset and a mean of 30±6 weeks at hospital admission, with a median disease day 7 since first symptoms. Most women (81%) were treated with hydroxychloroquine; 7% of women with severe disease and 65% of women with critical disease received remdesivir. All women with critical disease received either prophylactic or therapeutic anticoagulation during their admission. The median duration of hospital stay was 6 days (6 days severe group and 10.5 days critical group; P=.01). Intubation was usually performed around day 9 on patients who required it, and peak respiratory support for women with severe disease was performed on day 8. In women with critical disease, prone positioning was required in 20% of cases, the rate of acute respiratory distress syndrome was 70%, and reintubation was necessary in 20%. There was 1 case of maternal cardiac arrest, but there were no cases of cardiomyopathy or maternal death. Thirty-two of 64 (50%) women with coronavirus disease 2019 in this cohort delivered during their hospitalization (34% severe group and 85% critical group). Furthermore, 15 of 17 (88%) pregnant women with critical coronavirus disease 2019 delivered preterm during their disease course, with 16 of 17 (94%) pregnant women giving birth through cesarean delivery; overall, 15 of 20 (75%) women with critical disease delivered preterm. There were no stillbirths or neonatal deaths or cases of vertical transmission.
In pregnant women with severe or critical coronavirus disease 2019, admission into the hospital typically occurred about 7 days after symptom onset, and the duration of hospitalization was 6 days (6 severe group vs 12 critical group). Women with critical disease had a high rate of acute respiratory distress syndrome, and there was 1 case of cardiac arrest, but there were no cases of cardiomyopathy or maternal mortality. Hospitalization of pregnant women with severe or critical coronavirus disease 2019 resulted in delivery during the clinical course of the disease in 50% of this cohort, usually in the third trimester. There were no perinatal deaths in this cohort.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This paper characterizes the detailed sedimentology of a fluvial sandbody on Mars for the first time and interprets its depositional processes and palaeoenvironmental setting. Despite numerous ...orbital observations of fluvial landforms on the surface of Mars, ground‐based characterization of the sedimentology of such fluvial deposits has not previously been possible. Results from the NASA Mars Science Laboratory Curiosity rover provide an opportunity to reconstruct at fine scale the sedimentary architecture and palaeomorphology of a fluvial environment on Mars. This work describes the grain size, texture and sedimentary facies of the Shaler outcrop, reconstructs the bedding architecture, and analyses cross‐stratification to determine palaeocurrents. On the basis of bedset geometry and inclination, grain‐size distribution and bedform migration direction, this study concludes that the Shaler outcrop probably records the accretion of a fluvial barform. The majority of the outcrop consists of large‐scale trough cross‐bedding of coarse sand and granules. Palaeocurrent analyses and bedform reconstruction indicate that the beds were deposited by bedforms that migrated towards the north‐east, across the surface of a bar that migrated south‐east. Stacked cosets of dune cross‐bedding suggest aggradation of multiple bedforms, which provides evidence for short periods of sustained flow during Shaler deposition. However, local evidence for aeolian reworking and the presence of potential desiccation cracks within the outcrop suggest that fluvial deposition may have been intermittent. The uppermost strata at Shaler are distinct in terms of texture and chemistry and are inferred to record deposition from a different sediment dispersal system with a contrasting provenance. The outcrop as a whole is a testament to the availability of liquid water on the surface of Mars in its early history.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Self-report scales are widely used in cognitive neuroscience and psychology. However, they rest on the central assumption that respondents engage meaningfully. We hypothesise that this assumption ...does not hold for many patients, especially those with syndromes associated with frontotemporal lobar degeneration. In this study we investigated differences in response patterns on a visual analogue scale between people with frontotemporal degeneration and controls. We found that people with syndromes associated with frontotemporal lobar degeneration respond with more invariance and less internal consistency than controls, with Bayes Factors = 15.2 and 14.5 respectively indicating strong evidence for a group difference. There was also evidence that patient responses feature lower entropy. These results have important implications for the interpretation of self-report data in clinical populations. Meta-response markers related to response patterns, rather than the values reported on individual items, may be an informative addition to future research and clinical practise.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK