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To interpret how the thickness of the peripapillary retinal nerve fiber layer (RNFL) changes with increasing age, axial length, or anterior chamber depth as measured by spectral domain optical coherence tomography (OCT) in the normal elderly population in Taiwan. A total of 82 volunteers (143 eyes) were enrolled. Generalized estimating equations were used to evaluate the correlation. The RNFL was significantly thinner in the superonasal (p = 0.004), inferotemporal (p = 0.046), and temporolower (p = 0.009) segments with age. The same trend was also observed in the superotemporal (p = 0.330) segment, although it was not statistically significant. The global RNFL thickness decreased by 4.97 μm per decade (β = -0.497; p = 0.021), and thinning was significant in the superonasal (-9.90 μm per decade, p < 0.001) and temporolower (-6.78 μm per decade, p < 0.001) segments; the same trend showed borderline significance in the superotemporal (-6.96 μm per decade, p = 0.073) and inferotemporal (-7.23 μm per decade, p = 0.059) segments. In eyes with longer axial length, the RNFLs significantly decreased in the non-temporal segments. Global RNFL thickness decreased by 3.086 μm for each additional millimeter of axial length (β = -3.086; p < 0.001). Changes in RNFL thickness were correlated with age in the superonasal, superotemporal, inferotemporal, and temporolower segments, and were correlated with axial length in the non-temporal segments. Anterior chamber depth was not correlated with RNFL thickness.

Higher serum cholesterol levels have been associated with an increased risk of dry eye disease (DED). The relationship between statin (HMG‐CoA reductase inhibitor) use and DED in patients with hyperlipidemia remains unclear. To investigate the association between statin use and the risk of DED in patients with hyperlipidemia, we conducted a population‐based retrospective cohort study utilizing data from Taiwan's Longitudinal Generation Tracking Database. Patients were categorized into statin users and nonusers, with a 5‐year follow‐up period. The study identified patients with newly diagnosed hyperlipidemia, excluding those with prior DED diagnoses. Matching and adjustments for covariates resulted in 41,931 individuals in each group. Patients receiving statin therapy were compared with those unexposed. Cumulative exposure doses were also evaluated to assess dose–response relationships. The primary outcome was the incidence of DED diagnosed during the follow‐up period. Cox proportional hazards regression models estimated the risk of DED, and conditional logistic regression analyzed the dose–response effect of statin exposure. Among 41,931 matched pairs, statin users exhibited a slightly increased risk of developing DED compared with nonusers (adjusted hazard ratio, 1.06; 95% CI, 1.02–1.11; p < 0.01). However, no dose–response relationship was observed between statin exposure and DED risk. Statin use among patients with hyperlipidemia is associated with a marginally higher risk of DED. These findings underscore the importance of regular eye examinations in this patient population to facilitate early detection and management of DED.

This population-based retrospective cohort study investigated the effectiveness of erythropoietin (EPO) treatment in reducing the risk of age-related macular degeneration (AMD) in hemodialysis patients, using the National Health Insurance Research Data of Taiwan. From the database, we identified 147,318 end-stage renal disease (ESRD) patients on hemodialysis who had been diagnosed in 2000–2014 to establish the propensity-score-matched EPO user cohort and non-EPO user cohort with equal sample size of 15,992. By the end of 2016, the cumulative incidence of AMD in EPO users was about 3.29% lower than that in non-EPO users (Kaplan–Meier survival p < 0.0001). The risk of AMD was 43% lower in EPO users than in non-EPO users, with an adjusted hazard ratio (aHR) of 0.57 (95% confidence interval (CI) = 0.51–0.64) estimated in the multivariate Cox model. A significant negative dose–response relationship was identified between the EPO dosage and the risk of AMD (p < 0.0001). Another beneficial effect of EPO treatment was a reduced risk of both exudative AMD (aHR = 0.48, 95% CI = 0.40–0.61) and non-exudative AMD (aHR = 0.61, 95% CI = 0.53–0.69), also in similar dose–response relationships (p < 0.0001). Our findings suggest that EPO treatment for hemodialysis patients could reduce AMD risk in a dose–response relationship.

Background Monofocal necrotizing fasciitis (MONF) involves a single site in a rapidly progressing infection and necrosis of the fascia and surrounding soft tissue. Synchronous multifocal necrotizing fasciitis (SMNF), the simultaneous development of NF in multiple noncontiguous sites, is rarely reported. This study aimed to compare the clinical characteristics and outcomes between patients with SMNF and MONF, and to determine the risk factors of SMNF. Methods Our retrospective case-control study compared the clinical characteristics and outcomes, between January 2006 and January 2013, of patients with SMNF and of patients with MONF of the extremities. Results We enrolled 144 patients with NF of the extremities: 19 with SMNF and 125 with MONF. The duration of symptoms before admission was significantly shorter for the former than for the latter (1.7 days vs. 3.3 days, p  = 0.001); the prevalence of shock at the initial visit significantly higher (73.7% vs. 36%, p  = 0.002); and the total-case postoperative mortality rate significantly higher (68.4% vs. 14.4%, p  <  0.001). In further analysis of the total-case mortality, 9 in 13 SMNF deaths (69.2%) within 7 days after fasciotomy were in the majority while 13 with 28-day mortality (72.2%) was the majority of MONF deaths ( p  <  0.001). SMNF was significantly more likely to involve bacteremia (89.5% vs. 36%, p  <  0.001). Independent risk factors for SMNF were liver cirrhosis (LC) (odds ratio [OR] 6.0, p  = 0.001) and end-stage renal disease (ESRD) (OR 7.1, p  = 0.035). Gram-negative bacteria were most common in SMNF, and Gram-positive bacteria in MONF (83.3% vs. 53.3%, p  = 0.005). Vibrio species were the most common single microbial cause (35.4%) of all NF patients and were the overwhelming cause (73.7%) of SMNF. Staphylococcus aureus and group A β-hemolytic streptococcus (45.6%) were the other predominant causes of MONF while both (10.5%) rarely caused multifocal NF. Conclusions S MNF was more fulminant than was MONF. SMNF was attributable primarily to marine Gram-negative bacteria. Physicians should be aware of SMNF because of its extremely high mortality rate.

Considered a facet of behavioral impulsivity, response inhibition facilitates adaptive and goal-directed behavior. It is often assessed using the Stop-Signal Task (SST), which is presented on stand-alone computers under controlled laboratory conditions. Sample size may consequently be a function of cost or time and sample diversity constrained to those willing or able to attend the laboratory. Statistical power and generalizability of results might, in turn, be impacted. Such limitations may potentially be overcome via the implementation of web-based testing. The aim of this study was to investigate if there were differences between variables derived from a web-based SST when it was undertaken independently-that is, outside the laboratory, on any computer, and in the absence of researchers-versus when it was performed under laboratory conditions. We programmed a web-based SST in HTML and JavaScript and employed a counterbalanced design. A total of 166 individuals (mean age 19.72, SD 1.85, range 18-36 years; 146/166, 88% female) were recruited. Of them, 79 undertook the independent task prior to visiting the laboratory and 78 completed the independent task following their laboratory visit. The average time between SST testing was 3.72 (SD 2.86) days. Dependent samples and Bayesian paired samples t tests were used to examine differences between laboratory-based and independent SST variables. Correlational analyses were conducted on stop-signal reaction times (SSRT). After exclusions, 123 participants (mean age 19.73, SD 1.97 years) completed the SST both in the laboratory and independently. While participants were less accurate on go trials and exhibited reduced inhibitory control when undertaking the independent-compared to the laboratory-based-SST, there was a positive association between the SSRT of each condition (r=.48; P<.001; 95% CI 0.33-0.61). Findings suggest a web-based SST, which participants undertake on any computer, at any location, and in the absence of the researcher, is a suitable measure of response inhibition.

Viruses and virally derived particles have the intrinsic capacity to deliver molecules to cells, but the difficulty of readily altering cell-type selectivity has hindered their use for therapeutic delivery. Here, we show that cell surface marker recognition by antibody fragments displayed on membrane-derived particles encapsulating CRISPR–Cas9 protein and guide RNA can deliver genome editing tools to specific cells. Compared to conventional vectors like adeno-associated virus that rely on evolved capsid tropisms to deliver virally encoded cargo, these Cas9-packaging enveloped delivery vehicles (Cas9-EDVs) leverage predictable antibody–antigen interactions to transiently deliver genome editing machinery selectively to cells of interest. Antibody-targeted Cas9-EDVs preferentially confer genome editing in cognate target cells over bystander cells in mixed populations, both ex vivo and in vivo. By using multiplexed targeting molecules to direct delivery to human T cells, Cas9-EDVs enable the generation of genome-edited chimeric antigen receptor T cells in humanized mice, establishing a programmable delivery modality with the potential for widespread therapeutic utility. Cell-specific molecular delivery with enveloped delivery vehicles enables genome editing ex vivo and in vivo.

Subjective concerns of cognitive decline (SCD) often manifest in older adults who exhibit objectively normal cognitive functioning. This subjective-objective discrepancy is counter-intuitive when mounting evidence suggests that subjective concerns relate to future clinical progression to Alzheimer's disease, and so possess the potential to be a sensitive early behavioural marker of disease. In the current study, we aimed to determine whether individual variability in conscious awareness of errors in daily life might mediate this subjective-objective relationship. 67 cognitively-normal older adults underwent cognitive, SCD and mood tests, and an error awareness task. Poorer error awareness was not found to mediate a relationship between SCD and objective performance. Furthermore, non-clinical levels of depressive symptomatology were a primary driving factor of SCD and error awareness, and significantly mediated a relationship between the two. We were unable to show that poorer error awareness mediates SCD and cognitive performance in older adults. Our study does suggest, however, that underlying depressive symptoms influence both poorer error awareness and greater SCD severity. Error awareness is thus not recommended as a proxy for SCD, as reduced levels of error awareness do not seem to be reflected by greater SCD.

CRISPR-associated (Cas) enzymes have revolutionized biology by enabling RNA-guided genome editing. Homology-directed repair (HDR) in the presence of donor templates is currently the most versatile method to introduce precise edits following CRISPRCas- induced double-stranded DNA cuts, but HDR efficiency is generally low relative to end-joining pathways that lead to insertions and deletions (indels). We tested the hypothesis that HDR could be increased using a Cas9 construct fused to PRDM9, a chromatin remodeling factor that deposits histone methylations H3K36me3 and H3K4me3 to mediate homologous recombination in human cells. Our results show that the fusion protein contacts chromatin specifically at the Cas9 cut site in the genome to increase the observed HDR efficiency by threefold and HDR:indel ratio by fivefold compared with that induced by unmodified Cas9. HDR enhancement occurred in multiple cell lines with no increase in off-target genome editing. These findings underscore the importance of chromatin features for the balance between DNA repair mechanisms during CRISPR-Cas genome editing and provide a strategy to increase HDR efficiency.

Harmful microorganisms can be transferred to hands from contaminated surfaces people come into contact in daily life. Contaminated hands can transmit disease to one self as well as to others. A study was done to determine the extent to which hand hygiene practices and toilet door knobs contribute to the bacterial load of hands of toilet users in a medical school. Swabs were taken from a randomly selected sample of 60 medical students for bacterial count from both hands before and after toilet use and from door knobs of six toilets. Only 40 (66.7%) claimed they washed hands with soap. Significantly more females (83%) used soap to wash hands compared to males (50%). Bacterial load in the hands of both males and females showed an increase after toilet use. The increase was significant among male students. The dominant hand had a significantly higher bacterial load than the other. The mean bacterial load of male toilet door knobs (12 CFU/cm2) were significantly higher than of female toilet door knobs (2.5 CFU/cm2) (P<0.05). Staphylococcus aureus was isolated from the hands of 21 students. Toilets and washrooms should be designed so as to eliminate the sources of contamination of the hands.