Injectable biomimetic hydrogels have great potential for use in regenerative medicine as cellular delivery vectors. However, they can suffer from issues relating to hypoxia, including poor cell ...survival, differentiation, and functional integration owing to the lack of an established vascular network. Here we engineer a hybrid myoglobin:peptide hydrogel that can concomitantly deliver stem cells and oxygen to the brain to support engraftment until vascularisation can occur naturally. We show that this hybrid hydrogel can modulate cell fate specification within progenitor cell grafts, resulting in a significant increase in neuronal differentiation. We find that the addition of myoglobin to the hydrogel results in more extensive innervation within the host tissue from the grafted cells, which is essential for neuronal replacement strategies to ensure functional synaptic connectivity. This approach could result in greater functional integration of stem cell-derived grafts for the treatment of neural injuries and diseases affecting the central and peripheral nervous systems.
We investigated cerebral structural connectivity and its relationship to symptoms in never-medicated individuals with first-onset schizophrenia using diffusion tensor imaging (DTI).
We recruited ...subjects with first episode DSM-IV schizophrenia who had never been exposed to antipsychotic medication (n=34) and age-matched healthy volunteers (n=32). All subjects received DTI and structural magnetic resonance imaging scans. Patients' symptoms were assessed on the Positive and Negative Syndrome Scale. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values significantly correlated with symptom scores.
In patients with first-episode schizophrenia, positive symptoms correlated positively with FA scores in white matter associated with the right frontal lobe, left anterior cingulate gyrus, left superior temporal gyrus, right middle temporal gyrus, right middle cingulate gyrus, and left cuneus. Importantly, FA in each of these regions was lower in patients than controls, but patients with more positive symptoms had FA values closer to controls. We found no significant correlations between FA and negative symptoms.
The newly-diagnosed, neuroleptic-naive patients had lower FA scores in the brain compared with controls. There was positive correlation between FA scores and positive symptoms scores in frontotemporal tracts, including left fronto-occipital fasciculus and left inferior longitudinal fasciculus. This implies that white matter dysintegrity is already present in the pre-treatment phase and that FA is likely to decrease after clinical treatment or symptom remission.
Objectives. Systemic lupus erythematosus (SLE), a chronic illness with an unpredictable and variable course, profoundly affects the quality of life (QOL). General health questionnaires are used to ...assess QOL in SLE, but a disease-specific instrument could offer enhanced responsiveness and content validity. We detail the steps we took to develop and validate a new SLE-specific QOL instrument, SLEQOL. Methods. Rheumatology professionals nominated items that they felt were important determinants of QOL of SLE patients. One hundred SLE patients were asked to assess the importance and frequency of occurrence of these items and to suggest those that had not been listed. Item reduction was performed using Rasch model and factor analyses to create a new questionnaire in English. This final questionnaire was administered to a cohort of 275 patients to study its psychometric properties. Results. Fifty-one items covering a wide range of QOL concerns were identified. The patients’ responses led to the elimination of 11. The new questionnaire of 40 items was found to have Cronbach's alpha of 0.95 and to consist of eight domains covering physical, mental and social QOL issues. It has good test–retest reliability, poor to fair cross-sectional correlation with the SF-36, with poor correlation with lupus activity or damage indices. The SLEQOL was more responsive to change than the SF-36. Conclusions. We have developed a new 40-item SLEQOL in English and showed that it is valid for use in SLE patients in Singapore. It offers better content validity and responsiveness to change than the SF-36.
The Galactic Faraday rotation sky 2020 Hutschenreuter, S.; Anderson, C. S.; Betti, S. ...
Astronomy & astrophysics,
01/2022, Letnik:
657
Journal Article
Recenzirano
Odprti dostop
Aims.
This work provides an update to existing reconstructions of the Galactic Faraday rotation sky by processing almost all Faraday rotation data sets available at the end of the year 2020. ...Observations of extra-Galactic sources in recent years have further illuminated the previously underconstrained southern celestial sky, as well as parts of the inner disc of the Milky Way, along with other regions. This has culminated in an all-sky data set of 55 190 data points, thereby comprising a significant expansion on the 41 330 used in previous works. At the same time, this novelty makes an updated separation of the Galactic component a promising enterprise. The increased source density allows us to present our results in a resolution of about 1.3 × 10
−2
deg
2
(46.8 arcmin
2
), which is a twofold increase compared to previous works.
Methods.
As for previous Faraday rotation sky reconstructions, this work is based on information field theory, namely, a Bayesian inference scheme for field-like quantities that handles noisy and incomplete data.
Results.
In contrast to previous reconstructions, we find a significantly thinner and pronounced Galactic disc with small-scale structures exceeding values of several thousand rad m
−2
. The improvements can mainly be attributed to the new catalog of Faraday data, but are also supported by advances in correlation structure modeling within numerical information field theory. We also provide a detailed discussion on the statistical properties of the Faraday rotation sky and we investigate correlations with other data sets.
CD70 is an ideal target for antibody-based therapies because of its aberrant high expression in renal carcinomas and non-Hodgkin lymphomas and its highly restricted expression in normal tissues. The ...expression profiling of CD70 in carcinomas has been limited because of the lack of a CD70-specific reagent that works in formalin-fixed paraffin-embedded (FFPE) tissues.
We generated murine monoclonal antibodies (mAbs) specific for CD70 and validated their specificity by western blot analysis and developed a protocol for immunohistochemistry on FFPE tissues. CD70+ tumour cell lines were used for testing the anti-tumour activity of the anti-CD70 antibody-drug conjugate, SGN-75.
We report novel detection of CD70 expression in multiple cancers including pancreatic (25%), larynx/pharynx (22%), melanoma (16%), ovarian (15%), lung (10%), and colon (9%). Our results show that pancreatic and ovarian tumour cell lines, which express high levels of endogenous or transfected CD70, are sensitive to the anti-tumour activity of SGN-75 in vitro and in vivo.
Development of murine mAbs for robust and extensive screening of FFPE samples coupled with the detection of anti-tumour activity in novel indications provide rationale for expanding the application of SGN-75 for the treatment of multiple CD70 expressing cancers.
Abstract
Background
Major advances in management of common pleural diseases have taken place in the past decade. However, pleural diseases are often managed by physicians of diverse training ...background and research on implementation of new knowledge is scanty. We aim to evaluate the practice pattern in pleural medicine among physicians in Hong Kong, for identification of possible gaps for clinical service improvement.
Methods
The Hong Kong Thoracic Society undertook a cross-sectional questionnaire survey in 2019, targeting clinicians of various subspecialties in internal medicine and levels of experience (basic and higher trainees, specialists) from twelve regional hospitals of diverse service scopes throughout Hong Kong. Respondents were selected by non-probability quota sampling. The questionnaire tool consisted of 46 questions covering diagnostic and therapeutic aspects of common pleural diseases. The responses were anonymous, and analysed independently using SPSS statistics software.
Results
The survey collected 129 responses, 47(36%) were from clinicians specialized in respiratory medicine. Majority of the respondents (98%) managed pleural diseases, including performing pleural procedures in their practice. Fifty-five percent of all the respondents had not received any formal training in transthoracic ultrasonography. A significant proportion of clinicians were unaware of pleuroscopy for investigation of exudative pleural effusion, indwelling pleural catheter for recurrent malignant pleural effusion, and combined intra-pleural Alteplase plus DNase for treatment of pleural infection (30%, 15% and 70% of non-respiratory clinicians respectively). Significant heterogeneity was found in the management of pleural infection, malignant pleural effusion and pneumothorax among respiratory versus non-respiratory clinicians. Contributing factors to the observed heterogeneity included lack of awareness or training, limited accessibility of drugs, devices, or dedicated service support.
Conclusion
Significant heterogeneity in management of pleural diseases was observed among medical clinicians in Hong Kong. Continuous medical education and training provision for both specialists and non-specialists has to be strengthened to enhance the implementation of advances, improve quality and equity of healthcare provision in pleural medicine.
BACKGROUNDBariatric surgery can be effective in weight reduction and diabetes remission in some patients, but is expensive. The costs of bariatric surgery in patients with obesity and type 2 diabetes ...mellitus (T2DM) were explored here. METHODSPopulation-based retrospectively gathered data on patients with obesity and T2DM from the Hong Kong Hospital Authority (2006-2017) were evaluated. Direct medical costs from baseline up to 60 months were calculated based on the frequency of healthcare service utilization and dispensing of diabetes medication. Charlson Co-morbidity Index (CCI) scores and co-morbidity rates were measured to compare changes in co-morbidities between surgically treated and control groups over 5 years. One-to-five propensity score matching was applied. RESULTSOverall, 401 eligible surgical patients were matched with 1894 non-surgical patients. Direct medical costs were much higher for surgical than non-surgical patients in the index year (€36 752 and €5788 respectively; P < 0·001) mainly owing to the bariatric procedure. The 5-year cumulative costs incurred by surgical patients were also higher (€54 135 versus €28 603; P < 0·001). Although patients who had bariatric surgery had more visits to outpatient and allied health professionals than those who did not across the 5-year period, surgical patients had shorter length of stay in hospitals than non-surgical patients in year 2-5. Surgical patients had significantly better CCI scores than controls after the baseline measurement (mean 3·82 versus 4·38 at 5 years; P = 0·016). Costs of glucose-lowering medications were similar between two groups, except that surgical patients had significantly lower costs of glucose-lowering medications in year 2 (€973 versus €1395; P = 0.012). CONCLUSIONBariatric surgery in obese patients with T2DM is expensive, but leads to an improved co-morbidity profile, and reduced length of hospitalization.
Approximately 1700 Pg of soil carbon (C) are stored in the northern circumpolar permafrost zone, more than twice as much C than in the atmosphere. The overall amount, rate, and form of C released to ...the atmosphere in a warmer world will influence the strength of the permafrost C feedback to climate change. We used a survey to quantify variability in the perception of the vulnerability of permafrost C to climate change. Experts were asked to provide quantitative estimates of permafrost change in response to four scenarios of warming. For the highest warming scenario (RCP 8.5), experts hypothesized that C release from permafrost zone soils could be 19–45 Pg C by 2040, 162–288 Pg C by 2100, and 381–616 Pg C by 2300 in CO
2
equivalent using 100-year CH
4
global warming potential (GWP). These values become 50 % larger using 20-year CH
4
GWP, with a third to a half of expected climate forcing coming from CH
4
even though CH
4
was only 2.3 % of the expected C release. Experts projected that two-thirds of this release could be avoided under the lowest warming scenario (RCP 2.6). These results highlight the potential risk from permafrost thaw and serve to frame a hypothesis about the magnitude of this feedback to climate change. However, the level of emissions proposed here are unlikely to overshadow the impact of fossil fuel burning, which will continue to be the main source of C emissions and climate forcing.
Introduction: The perceptions of medical futility and decisions about termination of resuscitation (TOR) for out-of-hospital cardiac arrest (OHCA) are highly heterogeneous and dependent on the ...practice of the attending emergency physicians. The objective of this study was to report and investigate the knowledge, attitudes, and practices regarding medical futility and TOR during management of OHCA in Hong Kong. Methods: A cross-sectional survey was conducted among emergency medicine physicians in Hong Kong. The questionnaire assessed participants’ background, knowledge, attitudes, and behaviours concerning medical futility and TOR in management of OHCA. Composite scores were calculated to reflect knowledge, attitudes, and practices of OHCA treatment. Subgroup analysis and multiple regression analysis were used to explore the relationship between participants’ background, knowledge, attitudes, and behaviours. Results: The response rate to this survey was 57% (140/247). Independent predictors of less aggressive resuscitation in OHCA patients included status as a Fellow of the Hong Kong College of Emergency Medicine (β= -0.314, P=0.028) and being an Advanced Cardiac Life Support instructor (β= -0.217, P=0.032). There was no difference in aggressiveness of resuscitation in terms of years of clinical experience (β=0.015, P=0.921), knowledge of TOR (β=0.057, P=0.509), or attitudes about TOR (β= -0.103, P=0.214). The correlation between knowledge and attitudes was low (Spearman’s coefficient=0.02, P=0.795). Conclusion: Clinical practice and behaviour of TOR was not demonstrated to have associations with knowledge or attitude. Status as a Fellow of the Hong Kong College of Emergency Medicine or Advanced Cardiac Life Support instructor were the only two parameters identified that had significant relationships with earlier TOR in medically futile patients with OHCA.
PDF
