Analysis of chromosome positions in the interphase nucleus of Chinese hamster cells by laser-UV-microirradiation experiments

Unsynchronized cells of an essentially diploid strain of female Chinese hamster cells derived from lung tissue (CHL) were laser-UV-microirradiated (=257 nm) in the nucleus either at its central part or at its periphery. After 7–9 h postincubation with 0.5 mM caffeine, chromosome preparations were made in situ. Twenty-one and 29 metaphase spreads, respectively, with partial chromosome shattering (PCS) obtained after micro-irradiation at these two nuclear sites, were Q-banded and analyzed in detail. A positive correlation was observed between the frequency of damage of chromosomes and both their DNA content and length at metaphase. No significant difference was observed between the frequencies of damage obtained for individual chromosomes at either site of microirradiation. The frequency of joint damage of homologous chromosomes was low as compared to nonhomologous ones. Considerable variation was noted in different cells in the combinations of jointly shattered chromosomes. Evidence which justifies an interpretation of these data in terms of an interphase arrangement of chromosome territories is discussed. Our data strongly argue against somatic pairing as a regular event, and suggest a considerable variability of chromosome positions in different nuclei. However, present data do not exclude the possibility of certain non-random chromosomal arrangements in CHL-nuclei. The interphase chromosome distribution revealed by these experiments is compared with centromere-centromere, centromere-center and angle analyses of metaphase spreads and the relationship between interphase and metaphase arrangements of chromosomes is discussed

King's Parkinson's disease pain scale, the first scale for pain in PD: An international validation

Pain is a key unmet need and a major aspect of non‐motor symptoms of Parkinson's disease (PD). No specific validated scales exist to identify and grade the various types of pain in PD. We report an international, cross‐sectional, open, multicenter, one‐point‐in‐time evaluation with retest study of the first PD‐specific pain scale, the King's PD Pain Scale. Its seven domains include 14 items, each item scored by severity (0‐3) multiplied by frequency (0‐4), resulting in a subscore of 0 to 12, with a total possible score range from 0 to 168. One hundred seventy‐eight PD patients with otherwise unexplained pain (age [mean ± SD], 64.38 ± 11.38 y [range, 29‐85]; 62.92% male; duration of disease, 5.40 ± 4.93 y) and 83 nonspousal non‐PD controls, matched by age (64.25 ± 11.10 y) and sex (61.45% males) were studied. No missing data were noted, and floor effect was observed in all domains. The difference between mean and median King's PD Pain Scale total score was less than 10% of the maximum observed value. Skewness was marginally high (1.48 for patients). Factor analysis showed four factors in the King's PD Pain Scale, explaining 57% of the variance (Kaiser‐Mayer‐Olkin, 0.73; sphericity test). Cronbach's alpha was 0.78, item‐total correlation mean value 0.40, and item homogeneity 0.22. Correlation coefficients of the King's PD Pain Scale domains and total score with other pain measures were high. Correlation with the Scale for Outcomes in PD‐Motor, Non‐Motor Symptoms Scale total score, and quality of life measures was high. The King's PD Pain Scale seems to be a reliable and valid scale for grade rating of various types of pain in PD. © 2015 International Parkinson and Movement Disorder Societ

Non-motor predictors of 36-month quality of life after subthalamic stimulation in Parkinson disease.

To identify predictors of 36-month follow-up quality of life (QoL) outcome after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD). In this ongoing, prospective, multicenter international study (Cologne, Manchester, London) including 73 patients undergoing STN-DBS, we assessed the following scales preoperatively and at 6-month and 36-month follow-up: PD Questionnaire-8 (PDQ-8), NMSScale (NMSS), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). We analyzed factors associated with QoL improvement at 36-month follow-up based on (1) correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions and receiver operating characteristic curves using a dichotomized variable “QoL responders”/“non-responders”. At both follow-ups, NMSS total score, SCOPA-motor examination, and -complications improved and LEDD was reduced significantly. PDQ-8 improved at 6-month follow-up with subsequent decrements in gains at 36-month follow-up when 61.6% of patients were categorized as “QoL non-responders”. Correlations, linear, and logistic regression analyses found greater PDQ-8 improvements in patients with younger age, worse PDQ-8, and worse specific NMS at baseline, such as ‘difficulties experiencing pleasure’ and ‘problems sustaining concentration’. Baseline SCOPA scores were not associated with PDQ-8 changes. Our results provide evidence that 36-month QoL changes depend on baseline neuropsychological and neuropsychiatric non-motor symptoms burden. These findings highlight the need for an assessment of a wide range of non-motor and motor symptoms when advising and selecting individuals for DBS therapy

Relationship between distal radius fracture malunion and arm-related disability: A prospective population-based cohort study with 1-year follow-up

<p>Abstract</p> <p>Background</p> <p>Distal radius fracture is a common injury and may result in substantial dysfunction and pain. The purpose was to investigate the relationship between distal radius fracture malunion and arm-related disability.</p> <p>Methods</p> <p>The prospective population-based cohort study included 143 consecutive patients above 18 years with an acute distal radius fracture treated with closed reduction and either cast (55 patients) or external and/or percutaneous pin fixation (88 patients). The patients were evaluated with the disabilities of the arm, shoulder and hand (DASH) questionnaire at baseline (concerning disabilities before fracture) and one year after fracture. The 1-year follow-up included the SF-12 health status questionnaire and clinical and radiographic examinations. Patients were classified into three hypothesized severity categories based on fracture malunion; no malunion, malunion involving either dorsal tilt (>10 degrees) or ulnar variance (≥1 mm), and combined malunion involving both dorsal tilt and ulnar variance. Multivariate regression analyses were performed to determine the relationship between the 1-year DASH score and malunion and the relative risk (RR) of obtaining DASH score ≥15 and the number needed to harm (NNH) were calculated.</p> <p>Results</p> <p>The mean DASH score at one year after fracture was significantly higher by a minimum of 10 points with each malunion severity category. The RR for persistent disability was 2.5 if the fracture healed with malunion involving either dorsal tilt or ulnar variance and 3.7 if the fracture healed with combined malunion. The NNH was 2.5 (95% CI 1.8-5.4). Malunion had a statistically significant relationship with worse SF-12 score (physical health) and grip strength.</p> <p>Conclusion</p> <p>Malunion after distal radius fracture was associated with higher arm-related disability regardless of age.</p

Treatment of post-traumatic degenerative changes of the radio-carpal and distal radio-ulnar joints by combining radius, scaphoid, and lunate (RSL) fusion with ulnar head replacement

Distal radial fractures are a common type of fracture. In the case of intra-articular fractures, they often result in post-traumatic arthrosis. The objective of this study is to describe a novel alternative to the established salvage techniques for the treatment of post-traumatic arthrosis of the radio-carpal and distal radio-ulnar joints (DRUJ). Six patients with radio-carpal and DRUJ arthrosis were treated with a combined radius, scaphoid, and lunate (RSL) arthrodesis and as a Herbert ulnar head prosthesis. Follow-up consisted of both radiographic and functional assessments. Functional measurements were noted both pre- and postoperatively. No non-union or pseudoarthrosis was seen; neither did any of the ulnar head prostheses show loosening. Clinical examination showed an improvement in strength, pain, and range of movement, as well as a decrease in disability. Combining RSL arthrodesis with a Herbert ulnar head prosthesis, which deals with pain while retaining partial wrist movement, can be an alternative to established salvage procedures

Optimisation of UAVs‐SfM data collection in aeolian landform morphodynamics : a case study from the Gonghe Basin, China

UAVs‐SfM (Unmanned Aerial Vehicles‐ Structure from Motion) systems can generate high‐resolution 3D topographic models of aeolian landforms. To explore the optimisation of UAVs‐SfM for use in aeolian landform morphodynamics, this study tested flight parameters for two contrasting aeolian landform areas (free dune and blowout) to assess the 3D reconstruction accuracy of the UAVs survey compared with field point measurements using differential RTK‐GPS (Real‐time Kinematic‐Global Positioning System). The results reveal the optimum UAVs‐SfM flight set‐up at the free‐dune site was: flying height = 74 m, camera tilt angle = ‐90°, photo overlap ratio = 85%/70% (heading/sideways). The horizontal/vertical location error was around 0.028~0.055 m and 0.053‐0.069 m respectively, and a point cloud density of 463/m3 was found to generate a clear texture using these flying parameters. For the <20m deep blowout the optimum set‐up with highest accuracy and the lowest cliff texture distortion was: flying height = 74 m combined camera tilt angle = ‐90° and ‐60°, photo overlap ratio = 85%/70% (heading/sideways), and an evenly distributed GCPs (Ground Control Points) density of 42/km2 using these flying parameters. When the depth of the blowouts exceeded 40 m, the optimum flight/survey parameters changed slightly to account for more challenging cliff texture generation: flying height = 80 m (with ‐90° and ‐60°combined camera tilt angle), GCPs density = 63/km2 to generate horizontal and vertical location error of 0.024 m and 0.050 m respectively, and point cloud density of 2597.11/m3. The main external factors that affect the successful 3D reconstruction of aeolian landforms using UAVs‐SfM are the weather conditions, manipulation errors, and instrument system errors. The UAVs‐SfM topographic monitoring results demonstrate that UAVs provide a viable and robust means for aeolian landform morphodynamics monitoring. Importantly, the rapid and high precision 3D reconstruction processes were significantly advanced using the optimal flight parameters reported here

Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin

Abstract Background One of the most commonly used classes of anti-cancer drugs presently in clinical practice is the platinum-based drugs, including cisplatin. The efficacy of cisplatin therapy is often limited by the emergence of resistant tumours following treatment. Cisplatin resistance is multi-factorial but can be associated with increased DNA repair capacity, mutations in p53 or loss of DNA mismatch repair capacity. Methods RNA interference (RNAi) was used to reduce the transcription-coupled nucleotide excision repair (TC-NER) capacity of several prostate and colorectal carcinoma cell lines with specific defects in p53 and/or DNA mismatch repair. The effect of small inhibitory RNAs designed to target the CSB (Cockayne syndrome group B) transcript on TC-NER and the sensitivity of cells to cisplatin-induced apoptosis was determined. Results These prostate and colon cancer cell lines were initially TC-NER proficient and RNAi against CSB significantly reduced their DNA repair capacity. Decreased TC-NER capacity was associated with an increase in the sensitivity of tumour cells to cisplatin-induced apoptosis, even in p53 null and DNA mismatch repair-deficient cell lines. Conclusion The present work indicates that CSB and TC-NER play a prominent role in determining the sensitivity of tumour cells to cisplatin even in the absence of p53 and DNA mismatch repair. These results further suggest that CSB represents a potential target for cancer therapy that may be important to overcome resistance to cisplatin in the clinic

EAN consensus statement for management of patients with neurological diseases during the COVID‐19 pandemic

Background and purpose The recent SARS‐CoV‐2 pandemic has posed multiple challenges to the practice of clinical neurology including recognition of emerging neurological complications and management of coexistent neurological diseases. In a fast‐evolving pandemic, evidence‐based studies are lacking in many areas. This paper presents European Academy of Neurology (EAN) expert consensus statements to guide neurologists caring for patients with COVID‐19. Methods A refined Delphi methodology was applied. In round 1, statements were provided by EAN scientific panels (SPs). In round 2, these statements were circulated to SP members not involved in writing them, asking for agreement/disagreement. Items with agreement >70% were retained for round 3, in which SP co‐chairs rated importance on a five‐point Likert scale. Results were graded by importance and reported as consensus statements. Results In round one, 70 statements were provided by 23 SPs. In round two, 259/1061 SP member responses were received. Fifty‐nine statements obtained >70% agreement and were retained. In round three, responses were received from 55 co‐chairs of 29 SPs. Whilst general recommendations related to prevention of COVID‐19 transmission had high levels of agreement and importance, opinion was more varied concerning statements related to therapy. Conclusion This is the first structured consensus statement on good clinical practice in patients with neurological disease during the COVID‐19 pandemic that provides immediate guidance for neurologists. In this fast‐evolving pandemic, a rapid response using refined Delphi methodology is possible, but guidance may be subject to change as further evidence emerges

Non-motor predictors of 36-month quality of life after subthalamic stimulation in Parkinson disease

AbstractTo identify predictors of 36-month follow-up quality of life (QoL) outcome after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD). In this ongoing, prospective, multicenter international study (Cologne, Manchester, London) including 73 patients undergoing STN-DBS, we assessed the following scales preoperatively and at 6-month and 36-month follow-up: PD Questionnaire-8 (PDQ-8), NMSScale (NMSS), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). We analyzed factors associated with QoL improvement at 36-month follow-up based on (1) correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions and receiver operating characteristic curves using a dichotomized variable “QoL responders”/“non-responders”. At both follow-ups, NMSS total score, SCOPA-motor examination, and -complications improved and LEDD was reduced significantly. PDQ-8 improved at 6-month follow-up with subsequent decrements in gains at 36-month follow-up when 61.6% of patients were categorized as “QoL non-responders”. Correlations, linear, and logistic regression analyses found greater PDQ-8 improvements in patients with younger age, worse PDQ-8, and worse specific NMS at baseline, such as ‘difficulties experiencing pleasure’ and ‘problems sustaining concentration’. Baseline SCOPA scores were not associated with PDQ-8 changes. Our results provide evidence that 36-month QoL changes depend on baseline neuropsychological and neuropsychiatric non-motor symptoms burden. These findings highlight the need for an assessment of a wide range of non-motor and motor symptoms when advising and selecting individuals for DBS therapy.</jats:p