Enhanced Gene Delivery Mediated by Low Molecular Weight Chitosan/DNA Complexes: Effect of pH and Serum

This study was designed to systematically evaluate the influence of pH and serum on the transfection process of chitosan-DNA complexes, with the objective of maximizing their efficiency. The hydrodynamic diameter of the complexes, measured by dynamic light scattering (DLS), was found to increase with salt and pH from 243 nm in water to 1244 nm in PBS at pH 7.4 and aggregation in presence of 10% serum. The cellular uptake of complexes into HEK 293 cells assessed by flow cytometry and confocal fluorescent imaging was found to increase at lower pH and serum. Based on these data, new methodology were tested and high levels of transfection (>40%) were achieved when transfection was initiated at pH 6.5 with 10% serum for 8-24 h to maximize uptake and then the media was changed to pH 7.4 with 10% serum for an additional 24-40 h period. Cytotoxicity of chitosan/DNA complexes was also considerably lower than Lipofectamine. Our study demonstrates that the evaluation of the influence of important parameters in the methodology of transfection enables the understanding of crucial physicochemical and biological mechanisms which allows for the design of methodologies maximising transgene expression

Global Prevalence of Young-Onset Dementia: A Systematic Review and Meta-analysis

Importance: Reliable prevalence estimates are lacking for young-onset dementia (YOD), in which symptoms of dementia start before the age of 65 years. Such estimates are needed for policy makers to organize appropriate health care. Objective: To determine the global prevalence of YOD. Data sources: The PubMed, Embase, CINAHL, and PsycInfo databases were systematically searched for population-based studies on the prevalence of YOD published between January 1, 1990, and March 31, 2020. Study selection: Studies containing data on the prevalence of dementia in individuals younger than 65 years were screened by 2 researchers for inclusion in a systematic review and meta-analysis. Data extraction and synthesis: Prevalence estimates on 5-year age bands, from 30 to 34 years to 60 to 64 years, were extracted. Random-effects meta-analyses were conducted to pool prevalence estimates. Results were age standardized for the World Standard Population. Heterogeneity was assessed by subgroup analyses for sex, dementia subtype, study design, and economic status based on the World Bank classification and by meta-regression. Main outcomes and measures: Prevalence estimates of YOD for 5-year age bands. Results: A total of 95 unique studies were included in this systematic review, of which 74 with 2 760 379 unique patients were also included in 5-year age band meta-analyses. Studies were mostly conducted in Europe and in older groups in Asia, North America, and Oceania. Age-standardized prevalence estimates increased from 1.1 per 100 000 population in the group aged 30 to 34 years to 77.4 per 100 000 population in the group aged 60 to 64 years. This gives an overall global age-standardized prevalence of 119.0 per 100 000 population in the age range of 30 to 64 years, corresponding to 3.9 million people aged 30 to 64 years living with YOD in the world. Subgroup analyses showed prevalence between men and women to be similar (crude estimates for men, 216.5 per 100 000 population; for women, 293.1 per 100 000 population), whereas prevalence was lower in high-income countries (crude estimate, 663.9 per 100 000 population) compared with upper-middle-income (crude estimate, 1873.6 per 100 000 population) and lower-middle-income (crude estimate, 764.2 per 100 000 population) countries. Meta-regression showed that age range (P < .001), sample size (P < .001), and study methodology (P = .02) significantly influenced heterogeneity between studies. Conclusions and relevance: This systematic review and meta-analysis found an age-standardized prevalence of YOD of 119.0 per 100 000 population, although estimates of the prevalence in low-income countries and younger age ranges remain scarce. These results should help policy makers organize sufficient health care for this subgroup of individuals with dementia. Study registration: PROSPERO CRD42019119288This study was supported by the Gieskes-Strijbis Foundation, Alzheimer Netherlands, and the Dutch Young-Onset Dementia Knowledge Centre

Measurement of nasal dimensions and nasal indexes in patients with chronic dacryocystitis and its relationship to the sex of the patient

Chronic dacryocystitis is seen more commonly in females than males. This study was designed to determine why this should be the case. The nasal dimensions were measured and the nasal indexes in patients with chronic dacryocystitis (in both sexes) and in controls were calculated. Both of these values were smaller in females when compared with controls and males. It is concluded that besides other causes, the nasal dimensions in females were predisposing factors for their increased incidence of dacryocystitis

Measurements of Axial Length and Radius of Corneal Curvature in the Rabbit Eye

PubMedID: 9057929The axial length of the eye, the radius of the anterior corneal surface, and the diameter of the cornea were measured on 40 eyes of 20 New Zealand White rabbits. The ultrasonographic measurements of the axial length of the eye showed a mean value of 15.12 ± 0.51mm (15.33 ± 0.50mm in males, 14.96 ± 0.46mm in females). The mean corneal radius was 7.26 ± 0.26mm (7.18 ± 0.9mm in males, 7.32 ± 0.33 mm in females); the mean value of the difference in corneal curvature between two principle meridians was 0.21 ± 0.12mm; and the mean horizontal and vertical diameters of the cornea were 13.41 ± 0.34mm and 13.02 ± 0.30mm, respectively. Although the diameter of the cornea of rabbits was bigger than that of humans (average, horizontal 11.75mm, vertical 10.55mm), the axial length of the eye was 0.7 times that of humans (23-24mm), and the radius of corneal curvature was relatively smaller than that in humans (7.7-7.8mm)