UCBT recipients with TM are at high risk of EF related to low number of stem cells and prior alloimmunization after multiple blood transfusions. Here, we evaluated the safety and efficacy of ...double‐unit UCBT using TT‐containing conditioning regimens in TM. Retrospective analysis of children who underwent double‐unit UCBT for TM in the Prince of Wales Hospital between August 2007 and January 2017, and outcome of double‐unit UCBT for TM was compared with outcome of HLA‐matched sibling BMT. Ten patients, median age 4.2 years, received double‐unit UCBT. All patients except one engrafted at a median of 19 days. None of the patients with successful engraftment had grade III or IV aGVHD. Among nine patients with successful engraftment, six of nine patients evaluable after day 100 developed cGVHD. All patients with cGVHD were well controlled after treatment with steroids and/or supportive care and maintained good quality of life. In comparison with patients receiving BMT, those given UCBT had slower platelet recovery, and more cGVHD. With a median follow‐up of 272 months after BMT and 84 months after UCBT, the 8‐year OS after BMT and UCBT was 92% and 90% (P = .84), whereas 8‐year DFS after BMT and UCBT was 87% and 80% (P = .54). UCB could be an acceptable source of stem cells for transplantation of TM patients when HLA‐matched family bone marrow donors are NA.
Objective
Metabolic and atherosclerotic diseases are known risk factors for disability in old age, and can result in sarcopenia as well as cognitive impairment, which are both components of frailty ...syndrome. As muscle loss increases with ageing, it is unclear whether muscle loss per se, or the diseases themselves, are the underlying cause of physical frailty in those suffering from these diseases. We tested the hypothesis that metabolic and atherosclerotic diseases and cognitive impairment are associated with physical frailty independent of muscle loss in old age, and further examined their impact on the relationship between physical frailty and mortality.
Design
Prospective.
Setting
Community.
Participants
4000 community dwelling Chinese elderly ≥65 years.
Measurements
Diabetes, hypertension, stroke, heart disease, cognitive impairment, smoking, physical activity, waist hip ratio (WHR) and ankle-brachial index (ABI)) were recorded. Physical frailty measurements (grip-strength, chair-stands, stride length and 6-metre walks) were summarized into a composite frailty score (0–20), 0 being the most frail) according to quartiles of performance. Appendicular muscle mass (ASM) was measured using dual X-ray absorptiometry. Relationships between the score and covariates were analyzed. Cox regression was used to study the impact of metabolic and atnerosclerotic risk factors on the relationship between physical frailty and 6-year mortality.
Results
After adjustment for ASM, all metabolic diseases and indexes, and cognitive impairment were significantly associated with the composite physical frailty score in univariate analysis. In multivariate analysis, cognitive impairment, high WHR, diabetes, stroke and heart disease were all independently associated with higher physical frailty with adjustment for age, physical activity level and ASM. Hypertension was associated with physical frailty in men but not in women. In Cox regression, increased physical frailty was associated with higher 6-year mortality. The impact of metabolic and atherosclerotic risk factors was however only modest after adjustment for age and cognitive function.
Conclusion
Metabolic and atherosclerotic diseases and high WHR, was associated with physical frailty, independent of their adverse effect on cognitive function and muscle mass.
Objectives
It remains uncertain whether the favorable trend of reduction in physical disabilities has become reversed in the recent-born cohorts of older adults. This study aimed to compare the rate ...of decline with time in self-reported Instrumental Activity of Daily Living (IADL) difficulties, objective measurement of gait speed and grip strength, in three birth cohorts of Chinese older adults.
Design
A prospective cohort study.
Setting and Participants
Four thousand Chinese older adults aged 65 years or above in three birth cohorts (1934–1938, 1929–1933, 1905–1928) were recruited from the community in Hong Kong.
Measurements
Grip strength, gait speed and IADL difficulties were measured between 2001 to 2017. Joint models were used to examine the trajectories of grip strength, gait speed and IADL difficulties over time, and the interaction effect of age-by-cohort (or also age2-by-cohort) was also examined.
Results
The recently born cohort (1934 – 1938) had worse grip strength and more IADL difficulties at the same age than the earlier two cohorts (1929 – 1933; 1905 – 1928). Furthermore, the most recently born cohort also followed a more rapid decline longitudinally with a greater decline observed in gait speed, grip strength and IADL difficulties for women whereas a greater decline in grip strength and IADL difficulties for men.
Conclusions
The continuous improvement of physical limitations in old age may have halted and there appears to be a reversal of this favourable trend in the recent born cohort of older adults living in Hong Kong.
The genome of P. marneffei, the most important thermal dimorphic fungus causing respiratory, skin and systemic mycosis in China and Southeast Asia, possesses 23 polyketide synthase (PKS) genes and 2 ...polyketide synthase nonribosomal peptide synthase hybrid (PKS-NRPS) genes, which is of high diversity compared to other thermal dimorphic pathogenic fungi. We hypothesized that the yellow pigment in the mold form of P. marneffei could also be synthesized by one or more PKS genes.
All 23 PKS and 2 PKS-NRPS genes of P. marneffei were systematically knocked down. A loss of the yellow pigment was observed in the mold form of the pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants. Sequence analysis showed that PKS11 and PKS12 are fungal non-reducing PKSs. Ultra high performance liquid chromatography-photodiode array detector/electrospray ionization-quadruple time of flight-mass spectrometry (MS) and MS/MS analysis of the culture filtrates of wild type P. marneffei and the pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants showed that the yellow pigment is composed of mitorubrinic acid and mitorubrinol. The survival of mice challenged with the pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants was significantly better than those challenged with wild type P. marneffei (P<0.05). There was also statistically significant decrease in survival of pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants compared to wild type P. marneffei in both J774 and THP1 macrophages (P<0.05).
The yellow pigment of the mold form of P. marneffei is composed of mitorubrinol and mitorubrinic acid. This represents the first discovery of PKS genes responsible for mitorubrinol and mitorubrinic acid biosynthesis. pks12 and pks11 are probably responsible for sequential use in the biosynthesis of mitorubrinol and mitorubrinic acid. Mitorubrinol and mitorubrinic acid are virulence factors of P. marneffei by improving its intracellular survival in macrophages.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Family harmony, an important Confucian ideal in Chinese society is believed to determine family happiness and therefore health, but is this accurate? This is a qualitative study of 41 Hong Kong ...Chinese family members. Individual recorded interviews were thematically analysed describing perceived interactions between harmony, happiness and health. Family harmony comprised four components: communication, mutual respect, lack of conflict and family time notably 'Gou tong' (in Cantonese 溝通)—opportunity and willingness to spend time together—requiring good interpersonal communication, emphasized by female respondents. Lack of conflict was emphasized, while diverse values, parenting styles and financial difficulties were common causes of conflict. Respect required reciprocity. Family happiness comprised four elements: family harmony, an important pre-requisite; mutual caring and supportive orientation; sense of security emphasizing financial security in middle-class versus sense of togetherness in lower social class groups and contentment Healthy families were harmonious; 'typical' (children/two-parent/two-grandparent); happy; caring and respectful, with individual health and healthy behaviours. Family harmony, happiness and health are interrelated and built on a communicative, respectful, caring and contented set of attitudes, in particular allowing for family time. Harmony is apparently a core element of good family functioning.
Fast radio bursts (FRBs) are flashes of unknown physical origin
. The majority of FRBs have been seen only once, although some are known to generate multiple flashes
. Many models invoke magnetically ...powered neutron stars (magnetars) as the source of the emission
. Recently, the discovery
of another repeater (FRB 20200120E) was announced, in the direction of the nearby galaxy M81, with four potential counterparts at other wavelengths
. Here we report observations that localized the FRB to a globular cluster associated with M81, where it is 2 parsecs away from the optical centre of the cluster. Globular clusters host old stellar populations, challenging FRB models that invoke young magnetars formed in a core-collapse supernova. We propose instead that FRB 20200120E originates from a highly magnetized neutron star formed either through the accretion-induced collapse of a white dwarf, or the merger of compact stars in a binary system
. Compact binaries are efficiently formed inside globular clusters, so a model invoking them could also be responsible for the observed bursts.
Compared with young children who have acute lymphoblastic leukaemia (ALL), adolescents with ALL have unfavourable disease profiles and worse survival. However, limited data are available regarding ...the characteristics and outcomes of adolescents with ALL who underwent treatment in clinical trials. The aim of this study was to investigate the causes of treatment failure in adolescents with ALL.
We retrospectively analysed the outcomes of 711 children with ALL, aged 1-18 years, who were enrolled in five clinical trials of paediatric ALL treatment between 1993 and 2015.
Among the 711 children with ALL, 530 were young children (1-9 years at diagnosis) and 181 were adolescents (including 136 younger adolescents 10-14 years and 45 older adolescents 15-18 years). Compared with young children who had ALL, adolescents with ALL were less likely to have favourable genetic features and more likely to demonstrate poor early response to treatment. The 10-year overall survival and event-free survival rates were significantly lower among adolescents than among young children (77.9% vs 87.6%, P=0.0003; 69.7% vs 76.5%, P=0.0117). There were no significant differences in the 10-year cumulative incidence of relapse, but the 10-year cumulative incidence of treatment-related death (TRD) was significantly greater among adolescents (7.2%) than among young children (2.3%; P=0.002). Multivariable analysis showed that both younger and older adolescents (vs young children) had worse survival and greater incidence of TRD.
Adolescents with ALL had worse survival because they experienced a greater incidence of TRD. There is a need to investigate optimal treatment adjustments and novel targeted agents to achieve better survival rates (without excessive toxicity) among adolescents with ALL.
Thioamides antithyroid‐drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD‐induced agranulocytosis is important for clinical management. ...We performed a genome‐wide association study (GWAS) involving 20 patients with ATD‐induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single‐nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD‐induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8–103.7; P = 1.3 × 10‐24) and replication (OR = 37; 95% CI = 3.7–367.4; P = 9.6 × 10‐7). HLA‐B*38:02:01 was in complete linkage disequilibrium with rs185386680. High‐resolution HLA typing confirmed that HLA‐B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)‐induced agranulocytosis (OR = 265.5; 95% CI = 27.9–2528.0; P = 2.5 × 10‐14), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA‐B*38:02:01 in predicting CMZ/MMI‐induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.
Suspicious non-calcified mammographic findings have not been evaluated with modern mammographic technique, and the purpose of this work is to compare the likelihood of malignancy for those findings. ...To do this, 5018 consecutive mammographically guided biopsies performed during 2016-2019 at a large metropolitan, community-based hospital system were retrospectively reviewed. In total, 4396 were excluded for targeting calcifications, insufficient follow-up, or missing data. Thirty-seven of 126 masses (29.4%) were malignant, 44 of 194 asymmetries (22.7%) were malignant, and 77 of 302 architectural distortions (AD, 25.5%) were malignant. The combined likelihood of malignancy was 25.4%. Older age was associated with a higher likelihood of malignancy for each imaging finding type (all
≤ 0.006), and a possible ultrasound correlation was associated with a higher likelihood of malignancy when all findings were considered together (
= 0.012). Two-view asymmetries were more frequently malignant than one-view asymmetries (
= 0.03). There were two false-negative biopsies (98.7% sensitivity and 100% specificity). In conclusion, the 25.4% likelihood of malignancy confirms the recommendation for biopsy of suspicious, ultrasound-occult, mammographic findings. Mammographically guided biopsies were highly sensitive and specific in this study. Older patient age and a possible ultrasound correlation should raise concern given the increased likelihood of malignancy in those scenarios.
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