Advanced paternal age effects in neurodevelopmental disorders?review of potential underlying mechanisms

Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring, particularly with regard to increased risk for autism and schizophrenia. Conclusive evidence about how age-related changes in paternal gametes, or age-independent behavioral traits affect neural development is still lacking. Recent evidence suggests that the origins of APA effects are likely to be multidimensional, involving both inherited predisposition and de novo events. Here we provide a review of the epidemiological and molecular findings to date. Focusing on the latter, we present the evidence for genetic and epigenetic mechanisms underpinning the association between late fatherhood and disorder in offspring. We also discuss the limitations of the APA literature. We propose that different hypotheses relating to the origins of the APA effects are not mutually exclusive. Instead, multiple mechanisms likely contribute, reflecting the etiological complexity of neurodevelopmental disorders

Comparison of anti-vascular endothelial growth factors, laser treatments and a combination of the both for treatment of central retinal vein occlusion

AIM: To compare changes in visual acuity and macular edema in patients with central retinal vein occlusion (CRVO) treated with intravitreal injections of bevacizumab, macular grid photocoagulation combined with pan retinal photocoagulation (PRP), or both (bevacizumab+grid+PRP). METHODS: Our study is a retrospective cohort clinical study that examined patients that suffered from ischemic CRVO with macular edema. Study inclusion criteria were ischemic CRVO with macula edema and the availability of complete medical records for at least 12mo after treatment. Excluded were patients with diabetes or any other retinal disease. We reviewed the medical records of patients treated in one ophthalmology department-comparing changes in visual acuity and macular edema in patients treated with intravitreal injections of bevacizumab vs those that were treated with macular grid photocoagulation and PRP or both. The main outcome measures were the differences in best corrected visual acuity (BCVA) and in macular thickness, as assessed by optical coherence tomography, between the enrollment and the final follow up visits. RESULTS: Sixty-five patients met inclusion criteria. There were no statistically significant differences among the three groups in the mean changes in macular thickness as measured by ocular coherence tomography (131.5±41.2, 108.6±29.2, and 121.1±121.1, P=0.110), or in visual acuity (0.128±0.077, 0.088±0.057, and 0.095±0.065), for intravitreal injections, macular grid photocoagulation+PRP and a combination of the treatments, respectively, P=0.111. The proportions of patients with macular edema after treatment were: 26.1%, 28.6%, and 14.3%, respectively, P=0.499. CONCLUSION: Similar benefit was observed for intravitreal injections, laser photocoagulation, or a combined regimen in the treatment of CRVO. A non-statistically significant trend for reduction in macular edema was observed following combined treatment

Internal mechanical conditions in the soft tissues of a residual limb of a trans-tibial amputee

Most trans-tibial amputation (TTA) patients use a prosthesis to retain upright mobility capabilities. Unfortunately, interaction between the residual limb and the prosthetic socket causes elevated internal strains and stresses in the muscle and fat tissues in the residual limb, which may lead to deep tissue injury (DTI) and other complications. Presently, there is paucity of information on the mechanical conditions in the TTA residual limb during load-bearing. Accordingly, our aim was to characterize the mechanical conditions in the muscle flap of the residual limb of a TTA patient after donning the prosthetic socket and during load-bearing. Knowledge of internal mechanical conditions in the muscle flap can be used to identify the risk for DTI and improve the fitting of the prosthesis. We used a patient-specific modelling approach which involved an MRI scan, interface pressure measurements between the residual limb and the socket of the prosthesis and three-dimensional non-linear large-deformation finite-element (FE) modelling to quantify internal soft tissue strains and stresses in a female TTA patient during static load-bearing. Movement of the truncated tibia and fibula during load-bearing was measured by means of MRI and used as displacement boundary conditions for the FE model. Subsequently, we calculated the internal strains, strain energy density (SED) and stresses in the muscle flap under the truncated bones. Internal strains under the tibia peaked at 85%, 129% and 106% for compression, tension and shear strains, respectively. Internal strains under the fibula peaked at substantially lower values, that is, 19%, 22% and 19% for compression, tension and shear strains, respectively. Strain energy density peaked at the tibial end (104 kJ/m 3). The von Mises stresses peaked at 215 kPa around the distal end of the tibia. Stresses under the fibula were at least one order of magnitude lower than the stresses under the tibia. We surmise that our present patient-specific modelling method is an important tool in understanding the etiology of DTI in the residual limbs of TTA patients