Notes

A Novel Orthotopic Liver Cancer malignancy Product pertaining to Setting up a Human-like Growth Microenvironment.
While nuclear RNAi proteins have the potential to be a natural regulatory mechanism, careful study will be necessary to identify critical RNA drivers of normal physiology and disease.
To determine the efficacy and safety of dalteparin postoperative bridging treatment versus placebo for patients with atrial fibrillation or mechanical heart valves when warfarin is temporarily interrupted for a planned procedure.

Prospective, double blind, randomised controlled trial.

10 thrombosis research sites in Canada and India between February 2007 and March 2016.

1471 patients aged 18 years or older with atrial fibrillation or mechanical heart valves who required temporary interruption of warfarin for a procedure.

Random assignment to dalteparin (n=821; one patient withdrew consent immediately after randomisation) or placebo (n=650) after the procedure.

Major thromboembolism (stroke, transient ischaemic attack, proximal deep vein thrombosis, pulmonary embolism, myocardial infarction, peripheral embolism, or vascular death) and major bleeding according to the International Society on Thrombosis and Haemostasis criteria within 90 days of the procedure.

The rate of major thromboembolism within 90 days was 1.2% (eight events in 650 patients) for placebo and 1.0% (eight events in 820 patients) for dalteparin (P=0.64, risk difference -0.3%, 95% confidence interval -1.3 to 0.8). The rate of major bleeding was 2.0% (13 events in 650 patients) for placebo and 1.3% (11 events in 820 patients) for dalteparin (P=0.32, risk difference -0.7, 95% confidence interval -2.0 to 0.7). The results were consistent for the atrial fibrillation and mechanical heart valves groups.

In patients with atrial fibrillation or mechanical heart valves who had warfarin interrupted for a procedure, no significant benefit was found for postoperative dalteparin bridging to prevent major thromboembolism.

Clinicaltrials.gov NCT00432796.
Clinicaltrials.gov NCT00432796.
To investigate retinal sensitivity and fixation stability using microperimetry in children with retinopathy of prematurity (ROP).

Observational case series. Totally 51 preterm children who had been followed for ROP were examined in three groups (n=17 in each group). The groups were defined as children without ROP (group 1), children with spontaneously resolved ROP (group 2) and children who had laser treatment for ROP (group 3). All subjects underwent a detailed ophthalmic examination. Macular Analyzer Integrity Assessment Microperimetry was used to analyse macular light sensitivity and fixation stability. The results were compared between groups. The measurements were also analysed according to age, gender, birth weight and gestational age.

The mean age was 10.84±0.97 years, and 27 children were female. Mean average threshold (AT) for macular sensitivity was 25.5±2.1 decibel in group 1, 26.8±3.8 decibel in group 2 and 26.3±3.0 decibel in group 3. These differences were not statistically significant between the groups (p=0.067), but AT was abnormal in 29% of the whole study population. Outputs about fixation stability were similar between the three groups but fixation was unstable in 27% of the subjects. Mean AT was better in children ≥11 years old compared with the younger ones (p=0.022).

Preterm children may have some abnormalities in macular light sensitivity and fixation stability. These abnormalities may be more prominent in children less than 11 years old. ROP itself or the laser treatment seems not to affect macular light sensitivity and fixation stability.
Preterm children may have some abnormalities in macular light sensitivity and fixation stability. These abnormalities may be more prominent in children less than 11 years old. ROP itself or the laser treatment seems not to affect macular light sensitivity and fixation stability.
To set up the in vitro conditions for renewal of the conjunctival epithelium using healthy fragments of conjunctival tissue glued over an amniotic membrane.

We evaluated the capability of conjunctival tissue fragments to generate conjunctival cell outgrowth after seeding them onto amniotic membrane and culture plates; we then assessed conjunctival molecular marker expression by immunofluorescence. We also evaluated the efficiency of glueing the fragments over the amniotic membrane to determine the best setting and the feasibility of shipping preloaded amniotic membranes.

Epithelial outgrowth was detected in 65%-80% of conjunctival fragments starting 48-72 hours after glueing, without major differences between type of membrane preparation and fragment size. Within 6-13 days, a full epithelium covered the surface of the amniotic membrane. Specific marker expression (conjunctival epithelium, Muc1, K19, K13; stemness, p63; tight junctions, ZO-1) was detected. Results of the shipping test showed that only 31% of the fragments were still glued over the epithelial side of the membrane within 24 hours compared to more than 90% of fragments stayed attached in the remaining conditions.

The in vitro regeneration of conjunctival epithelium following outgrowth from conjunctival tissue fragments glued over an amniotic membrane may offer a viable strategy to renew the epithelium in vivo once applied over the ocular surface at the recipient site.
The in vitro regeneration of conjunctival epithelium following outgrowth from conjunctival tissue fragments glued over an amniotic membrane may offer a viable strategy to renew the epithelium in vivo once applied over the ocular surface at the recipient site.
Fuchs' uveitis syndrome (FUS) is one of the frequently misdiagnosed uveitis entities, which is partly due to the absence of internationally recognised diagnostic criteria. This study was performed to develop and evaluate a set of revised diagnostic criteria for FUS.

The clinical data of Chinese patients with FUS and patients with non-FUS were collected and analysed from a tertiary referral centre between April 2008 and December 2020. A total of 593 patients with FUS and 625 patients with non-FUS from northern China were enrolled for the development of diagnostic criteria for FUS. Three hundred and seventy-seven patients with FUS and 503 patients with non-FUS from southern China were used to validate the criteria. Clinical symptoms and ocular signs were collected from all patients with FUS and patients with non-FUS. Multivariate two-step cluster analysis, logistic regression and decision tree algorithms in combination with the clinical judgement of uveitis experts were used to revise diagnostic criteria for FUS.

Three essential findings including diffuse iris depigmentation, absence of posterior synechiae, mild inflammation in the anterior chamber at presentation and five associated findings including mostly unilateral involvement, cataract, vitreous opacities, absence of acute symptoms and characteristic iris nodules were used in the development of FUS diagnostic criteria. All essential findings were required for the diagnosis of FUS, and the diagnosis was further strengthened by the presence of associated findings.

Revised diagnostic criteria for FUS were developed and validated by analysing data from Chinese patients and showed a high sensitivity (96.55%) and specificity (97.42%).
Revised diagnostic criteria for FUS were developed and validated by analysing data from Chinese patients and showed a high sensitivity (96.55%) and specificity (97.42%).
To evaluate subtypes and characteristics of dry eye (DE) using conventional tests and dynamic tear interferometry, and to investigate determinants of disease severity in each DE subtype.

309 patients diagnosed with DE and 69 healthy controls were prospectively enrolled. All eyes were evaluated using Ocular Surface Disease Index (OSDI), Schirmer's test I (ST1) and Meibomian gland dysfunction (MGD) grade were analysed. The tear interferometric pattern and lipid layer thickness were determined using DR-1α and LipiView II, respectively.

Dynamic interferometric analysis revealed 56.6% of patients with DE exhibited Jupiter patterns, indicative of aqueous-deficiency, while 43.4% exhibited crystal patterns, indicative of lipid deficiency. These findings were in accordance with classification based on ST1 scores and MGD grade. Conventional assessment indicated 286 patients exhibited evidence of evaporative DE (EDE) due to MGD, while only 11 exhibited signs of pure aqueous-deficient DE (pure ADDE, only ST1 ≤5 mm)ric tear analysis to determine the most appropriate treatment for each DE patient.
To compare the preoperative biometric data and the refractive accuracy of cataract surgery among major surgical sites in a nationwide multicentre study.

We prospectively obtained the preoperative biometric data of 2143 eyes of 2143 consecutive patients undergoing standard cataract surgery at major 12 facilities and compared the preoperative biometry as well as the postoperative refractive accuracy among them.

We found significant differences in most preoperative variables, such as axial length (one-way analysis of variance, p=0.003), anterior chamber depth (p<0.001), lens thickness (p<0.001) and central corneal thickness (p<0.001), except for mean keratometry (p=0.587) and corneal astigmatism (p=0.304), among the 12 surgical sites. The prediction error using the Sanders-Retzlaff-Kraff/Theoretical (SRK/T formula was significantly more hyperopic than that using the Barrett Universal II formula (paired t-test, p<0.001). The absolute error using the SRK/T formula was significantly larger than thifferent among the 12 facilities. Our findings highlight the importance of individual optimisation of these formulas at each facility, especially in consideration of these biometric variations.Trial registration numberClinical Trial Registry; 000039976.CAR T cell therapy remains ineffective in solid tumors, due largely to poor infiltration and T cell suppression at the tumor site. Wortmannin T regulatory (Treg) cells suppress the immune response via inhibitory factors such as transforming growth factor-β (TGF-β). Treg cells expressing the C-C chemokine receptor 8 (CCR8) have been associated with poor prognosis in solid tumors. We postulated that CCR8 could be exploited to redirect effector T cells to the tumor site while a dominant-negative TGF-β receptor 2 (DNR) can simultaneously shield them from TGF-β. We identified that CCL1 from activated T cells potentiates a feedback loop for CCR8+ T cell recruitment to the tumor site. This sustained and improved infiltration of engineered T cells synergized with TGF-β shielding for improved therapeutic efficacy. Our results demonstrate that addition of CCR8 and DNR into CAR T cells can render them effective in solid tumors.Neuropathological staging studies have suggested that tau pathology spreads through the brain in Alzheimer's disease (AD) and other tauopathies, but it is unclear how neuroanatomical connections, spatial proximity, and regional vulnerability contribute. In this study, we seed tau pathology in the brains of nontransgenic mice with AD tau and quantify pathology development over 9 months in 134 brain regions. Network modeling of pathology progression shows that diffusion through the connectome is the best predictor of tau pathology patterns. Further, deviations from pure neuroanatomical spread are used to estimate regional vulnerability to tau pathology and identify related gene expression patterns. Last, we show that pathology spread is altered in mice harboring a mutation in leucine-rich repeat kinase 2. While tau pathology spread is still constrained by anatomical connectivity in these mice, it spreads preferentially in a retrograde direction. This study provides a framework for understanding neuropathological progression in tauopathies.
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