Mckayfleming8170
supported by the National Key Research and Development Program of China (2018YFC0910303), National Natural Science Foundation of China (81801592, 82101876), Clinical Research Plan of SHDC (SHDC2020CR4011), Ruijin Hospital Youth Incubation Project (KY2021607) and Shanghai Pujiang Young Rheumatologists Training Program (SPROG202006).
Post-traumatic syringomyelia (PTS) affects patients with chronic spinal cord injury (SCI) and is characterized by progressive deterioration of neurological symptoms. To improve surgical treatment, we studied the therapeutic effects of neuroepithelial-like stem cells (NESCs) derived from induced pluripotent stem cells (iPSCs) in a rat model of PTS. To facilitate clinical translation, we studied NESCs derived from Good Manufacturing Practice (GMP)-compliant iPSCs.
Human GMP-compliant iPSCs were used to derive NESCs. Cryo-preserved NESCs were used off-the-shelf for intraspinal implantation to PTS rats 1 or 10 weeks post-injury, and rats were sacrificed 10 weeks later. In vivo cyst volumes were measured with micro-MRI. Phenotypes of differentiated NESCs and host responses were analyzed by immunohistochemistry.
Off-the-shelf NESCs transplanted to PTS rats 10 weeks post-injury reduced cyst volume. The grafted NESCs differentiated mainly into glial cells. Importantly, NESCs also stimulated tissue repair. They reduced the density of glial scars and neurite-inhibiting chondroitin sulfate proteoglycan 4 (CSPG4), stimulated host oligodendrocyte precursor cells to migrate and proliferate, reduced active microglia/macrophages, and promoted axonal regrowth after subacute as well as chronic transplantation.
Significant neural repair promoted by NESCs demonstrated that human NESCs could be used as a complement to standard surgery in PTS. We envisage that future PTS patients transplanted with NESCs will benefit both from eliminating the symptoms of PTS, as well as a long-term improvement of the neurological symptoms of SCI.
This work was supported by Vinnova (2016-04134), Karolinska Institutet StratRegen, and the Chinese Scholarship Council.
This work was supported by Vinnova (2016-04134), Karolinska Institutet StratRegen, and the Chinese Scholarship Council.Allele frequency distributions and statistical forensic parameters of 19 autosomal STR loci in a sample of 535 unrelated healthy Hui individuals from Yunnan province were estimated. A total of 236 alleles at these loci were identified and their corresponding allele frequencies ranged from 0.000935 to 0.527103. Penta E is the most informative in Hui population, whereas TPOX showed the lowest. All of the STR loci reached the Hardy-Weinberg equilibrium after Bonferroni correction. The combined discrimination power and probability of excluding paternity of the 19 STR loci were 0.999 999 999 999 999 999 999 984 47 16 and 0.999 999 988, respectively. Furthermore, the genetic relationship between the Yunnan Hui population and other 8 different Hui groups or 25 previously investigated groups residing in other areas of China were also estimated based on pairwise genetic distance. These results suggest that the 19 STR loci are highly polymorphic, which is suitable for forensic personal identification and paternity testing.
Compare overall survival (OS) and breast cancer-specific survival (BCSS) outcomes of breast conservative therapy (BCT) and mastectomy in a large cohort of patients with early-stage triple negative breast cancer (TNBC), using a propensity score-based matching approach.
Surveillance, Epidemiology, and End Results (SEER) database was used to study the role of RT in early stage TNBC. Primary end points were OS and BCSS. Cox proportional hazard regression models and Kaplan-Meier plots were used to generate the desired outcomes. Propensity score matching was done to minimize bias.
12,761 patients with T1-2N0M0 TNBC as their first malignancy were retrieved. Of these 7237 had lumpectomy with RT, and 5524 had mastectomy only. Age, race, marital status, tumor laterality, grade and stage, and receipt of chemotherapy were prognostic variables for OS and BCSS. Among 4848 matched subjects, the 5-year OS was significantly higher in patients with lumpectomy and RT (89%) compared to mastectomy alone (84.5%) (p-value <0.001). Similarly, BCSS was significantly higher in patients with lumpectomy and RT (93%) compared to mastectomy alone (91%) (p-value <0.001). On subgroup analysis, patients who are younger than 40 had similar survival outcomes after either mastectomy alone or lumpectomy with RT. However, those who are older than 60, have any grade or T stage had better survival outcomes with lumpectomy and RT.
Overall, lumpectomy followed by RT is associated with better OS and BCSS compared to mastectomy in T1-2N0M0 TNBC patients. Further research is needed to determine the optimal treatment strategy for specific patient subgroups.
Overall, lumpectomy followed by RT is associated with better OS and BCSS compared to mastectomy in T1-2N0M0 TNBC patients. Further research is needed to determine the optimal treatment strategy for specific patient subgroups.
Real-world (RW) data may provide valuable information on the effectiveness and safety of medicines, which is particularly relevant for clinicians, patients and third-party payers. Evidence on the effectiveness of palbociclib plus fulvestrant is scarce, which highlights the need of additional studies. The aim of this study was to evaluate the effectiveness of palbociclib plus fulvestrant in advanced breast cancer (ABC).
We conducted a population-based retrospective cohort study and cases of interest were identified through the Portuguese National Cancer Registry database and additional data sources. Patients aged≥18 years, diagnosed with ABC and exposed to palbociclib plus fulvestrant between May 31, 2017 and March 31, 2019 were included. selleck kinase inhibitor Patients were followed-up until death or cut-off date (February 28, 2021). Primary outcome was rw-progression-free survival (rwPFS). Secondary outcomes were rw-overall survival (rwOS), rw-time to palbociclib failure (rwTPF) and rw-time to next treatment (rwTTNT).
A total of 210 patients were included. Median age was 58 years (range 29-83) and 99.05% were female. Median follow-up time was 23.22 months and, at cut-off date, treatment had been discontinued in 189 patients, mainly due to disease progression (n=152). Median rwPFS was 7.43 months (95% confidence interval [CI] 6.28-9.05) and 2-year rwPFS was 16.65% (95%CI 11.97-22.00). Median rwOS was 24.70 months (95%CI 21.58-29.27), median rwTPF was 7.5 months (95%CI 6.51-9.08) and median rwTTNT was 11.74 months (95%CI 10.33-14.08).
Palbociclib plus fulvestrant seems an effective treatment for ABC in real-world context. Compared to registrations studies, rwPFS and rwOS were shorter in real-life setting.
Palbociclib plus fulvestrant seems an effective treatment for ABC in real-world context. Compared to registrations studies, rwPFS and rwOS were shorter in real-life setting.During adolescence, rodents disperse from their natal site, find a new home, and navigate social relationships and threats. Although rats and mice in the laboratory cannot fully express these natural behaviors, they show striking changes in their affective and cognitive behavior across the adolescent period. In some laboratory-based behavior metrics, adolescent rodents fail to show the same behaviors expressed by adults, but in other metrics, adolescent behavioral performance is more robust or more flexible than at other ages. These data are often interpreted in light of proximate level analysis of development of neural circuits. It is also informative to attempt ultimate-level explanations and consider how sex and species-specific adolescent behavioral changes support dispersal, foraging, and social interactions in the wild.
To evaluate the associations between walking frequency and social activity as well as the potential moderating role of walkability in these relationships.
This study employed a cross-sectional design with a sensitivity analysis and techniques against common methods bias. The study population was community-dwelling older adults aged 60 years or more. A total of 927 older adults participated in the study after G*Power 3.1.9.4 was used to calculate the minimum sample size required for the study. A hierarchical linear regression (HLR) analysis was used to analyse the data.
Older adults who walked 'many times' to socialize reported higher social activity than their peers who walked 'sometimes' or less frequently. Older adults who walked 'sometimes', 'many times' and 'always' for economic reasons reported higher social activity than their peers who did not walk at all. Neighborhood walkability positively moderated the association between at least one indicator of walking and social activity.
Frequent walking may better contribute to social activity among seniors in more walkable neighborhoods. Community design interventions aimed at enhancing walkability can encourage walking and social activity among seniors.
Frequent walking may better contribute to social activity among seniors in more walkable neighborhoods. Community design interventions aimed at enhancing walkability can encourage walking and social activity among seniors.
Resilience and optimism have been proposed as psychological resources which may help to cope better with work demands, preventing negative consequences of stress, whereas external locus of control (ELC) is considered an intra-psychic vulnerability factor associated with increased burnout. Noteworthy, the specific role of these overlapping constructs on the prevention of burnout and promotion of work engagement, respectively, remains unclear.
The main aim of this study was to compare the differential significance of resilience and optimism, joined with ELC, on the prediction of burnout and work engagement.
A sample of 265 professional caregivers of dependent older adults was assessed using an extensive standardized protocol. Optimism and ELC were measured using the Palenzuela's Battery of Generalised Expectancies of Control, and the Connor-Davidson Scale was used to estimate resilience. Moreover, the Maslach Burnout Inventory and the Utrecht Work Engagement Scale were used to measure burnout and work engagement, respectively. Different hierarchical regression models were conducted with burnout and work engagement as dependent factors.
The results showed that more than half (51%) variance in resilience was accounted by grounded optimism scores. The ELC was the main explanatory factor of burnout, whereas optimism and resilience were the best predictors of work engagement. Finally, even after controlling the effect of resilience, the effect of optimism remained significant for predicting work engagement.
These findings support distinctive role resilience and optimism, two closely related psychological constructs, for promoting work engagement and reducing burnout in professional caregivers of older adults.
These findings support distinctive role resilience and optimism, two closely related psychological constructs, for promoting work engagement and reducing burnout in professional caregivers of older adults.
The role of prophylactic vitamin D supplementation in prevention and treatment of respiratory infections and other related pathologies has been extensively explored with conflicting results. The aim of this systematic review and meta-analysis was to evaluate the prophylactic and therapeutic effects of vitamin D administration on respiratory infections.
A systematic search was performed and randomized controlled trials (RCTs) of vitamin D supplementation and a total of 65 RCTs involving 50,554 participants were included.
The overall incidence of respiratory infections in terms of count data (OR 0.87; 95%CI [0.80-0.95]; p=0.0028; I
=43%) and event rate (IRR 0.81; 95%CI [0.70-0.95]; p=0.010; I
=79%) was significantly reduced in the intervention group. However, no effect of vitamin D on duration or upper respiratory tract infection severity was observed following the overall analysis. Subgroup analyses revealed more details regarding the protective effect of particular dose ranges, administration frequencies and trial durations on different disease types.
