Oscillatory Photodynamic Therapy for Choroidal Neovascularization and Central Serous Retinopathy; a Pilot Study

Purpose: To report the preliminary results of oscillatory photodynamic therapy (OPDT) for choroidal neovascularization (CNV) and central serous retinopathy (CSR). Methods: This study included 7 eyes of 6 patients with CSR (2 eyes), idiopathic CNV (2 eyes), CNV due to age-related macular degeneration (AMD) (2 eyes), and peripapillary CNV secondary to presumed ocular histoplasmosis syndrome (1 eye). Intravenous verteporfin (6 mg/m2 body surface area) was infused over 10 minutes followed by oscillating laser (wavelength 689 nm) covering slightly beyond the entire lesion. An Area Centralis lens was applied and laser was delivered (600 mW/cm2 fluence rate and 50 J/cm2 dose). Intravitreal bevacizumab and dexamethasone combination therapy was used with OPDT in 4 eyes with CNV; intravitreal dexamethasone and triamcinolone acetonide were injected in the other eye with CNV. Clinical examination, funduscopy, fluorescein angiography, and optical coherence tomography (OCT) were performed at baseline and after treatment. Results: After mean follow-up of 7.1±5.1 months, visual acuity improved from 0.87±0.69 logMAR (20/160) to 0.60±0.65 logMAR (20/80) (P = 0.027); central foveal thickness decreased from 322±62.1 to 240.7±34.8 microns as measured by OCT (P = 0.018). Fluorescein angiography and OCT demonstrated cessation of vascular leakage, and resolution of hemorrhage and subretinal fluid in all eyes. No adverse events or recurrence were noted. Conclusion: OPDT was effective in treating CNV lesions and CSR. OPDT may be an improvement on standard PDT due to reduced side effects, thermal damage and scarring

Achieving very long lifetimes in optical lattices with pulsed cooling

We have realized a one dimensional optical lattice for individual atoms with a lifetime >300 s, which is 5 times longer than previously reported. In order to achieve this long lifetime, it is necessary to laser cool the at-oms briefly every 20 s to overcome heating due to technical fluctuations in the trapping potential. Without cooling, we observe negligible atom loss within the first 20 s followed by an exponential decay with a 62 s time constant. We obtain quantitative agreement with the measured fluctuations of the trapping potential and the corresponding theoretical heating rates.Comment: 4 pages, 5 figure

Fragile Complexity of Comparison-Based Algorithms

We initiate a study of algorithms with a focus on the computational complexity of individual elements, and introduce the fragile complexity of comparison-based algorithms as the maximal number of comparisons any individual element takes part in. We give a number of upper and lower bounds on the fragile complexity for fundamental problems, including Minimum, Selection, Sorting and Heap Construction. The results include both deterministic and randomized upper and lower bounds, and demonstrate a separation between the two settings for a number of problems. The depth of a comparator network is a straight-forward upper bound on the worst case fragile complexity of the corresponding fragile algorithm. We prove that fragile complexity is a different and strictly easier property than the depth of comparator networks, in the sense that for some problems a fragile complexity equal to the best network depth can be achieved with less total work and that with randomization, even a lower fragile complexity is possible

Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes

T lymphocytes utilize amoeboid migration to navigate effectively within complex microenvironments. The precise rearrangement of the actin cytoskeleton required for cellular forward propulsion is mediated by actin regulators, including the actin‐related protein 2/3 (Arp2/3) complex, a macromolecular machine that nucleates branched actin filaments at the leading edge. The consequences of modulating Arp2/3 activity on the biophysical properties of the actomyosin cortex and downstream T cell function are incompletely understood. We report that even a moderate decrease of Arp3 levels in T cells profoundly affects actin cortex integrity. Reduction in total F‐actin content leads to reduced cortical tension and disrupted lamellipodia formation. Instead, in Arp3‐knockdown cells, the motility mode is dominated by blebbing migration characterized by transient, balloon‐like protrusions at the leading edge. Although this migration mode seems to be compatible with interstitial migration in three‐dimensional environments, diminished locomotion kinetics and impaired cytotoxicity interfere with optimal T cell function. These findings define the importance of finely tuned, Arp2/3‐dependent mechanophysical membrane integrity in cytotoxic effector T lymphocyte activities

Myelomatosis with type III hyperlipoproteinemia - clinical and metabolic studies

We investigated the metabolism of intermediate-density lipoproteins (IDL [1.006 to 1.019 g per milliliter]) and low-density lipoproteins (LDL [1.019 to 1.063 g per milliliter]) in two men with Type III hyperlipoproteinemia associated with myelomatosis. In vivo kinetic studies using Radio-labeled autologous lipoproteins demonstrated a greatly reduced fractional catabolic rate of IDL, relative to control values (patients vs. normal, 0.006 and 0.025 per hour vs. 0.20±0.08 per hour [mean ±S.E.M.]) and a greatly prolonged IDL-to-LDL conversion time (45 and 17 hours vs. 5.4±1.6 hours). In studies in vitro, LDL from both patients failed to bind to the LDL receptor of normal blood lymphocytes, whereas LDL from subjects with familial Type III hyperlipoproteinemia bound normally to the receptor. In one patient immunoglobulin was shown to be associated with IDL and LDL. Thus, hyperlipoproteinemia reflected an impaired metabolism of IDL, probably secondary to the binding of immunoglobulin to the lipoproteins. A similar impairment of receptor-mediated LDL catabolism did not elevate the plasma LDL concentration because of the low IDL-to-LDL conversion rate

ÁREA DE PRESIDENCIA [Material gráfico]

Forma parte del reportaje fotográfico sobre la inauguración en los años 40 del nuevo edificio institucional del Cabildo de Gran CanariaCopia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201

Identification of neural oscillations and epileptiform changes in human brain organoids

Brain organoids represent a powerful tool for studying human neurological diseases, particularly those that affect brain growth and structure. However, many diseases manifest with clear evidence of physiological and network abnormality in the absence of anatomical changes, raising the question of whether organoids possess sufficient neural network complexity to model these conditions. Here, we explore the network-level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex network dynamics reminiscent of intact brain preparations. We demonstrate highly abnormal and epileptiform-like activity in organoids derived from induced pluripotent stem cells from individuals with Rett syndrome, accompanied by transcriptomic differences revealed by single-cell analyses. We also rescue key physiological activities with an unconventional neuroregulatory drug, pifithrin-α. Together, these findings provide an essential foundation for the utilization of brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery

Requirement of Podocalyxin in TGF-Beta Induced Epithelial Mesenchymal Transition

Epithelial mesenchymal transition (EMT) is characterized by the development of mesenchymal properties such as a fibroblast-like morphology with altered cytoskeletal organization and enhanced migratory potential. We report that the expression of podocalyxin (PODXL), a member of the CD34 family, is markedly increased during TGF-β induced EMT. PODXL is enriched on the leading edges of migrating A549 cells. Silencing of podocalyxin expression reduced cell ruffle formation, spreading, migration and affected the expression patterns of several proteins that normally change during EMT (e.g., vimentin, E-cadherin). Cytoskeletion assembly in EMT was also found to be dependent on the production of podocalyin. Compositional analysis of podocalyxin containing immunoprecipitates revealed that collagen type 1 was consistently associated with these isolates. Collagen type 1 was also found to co-localize with podocalyxin on the leading edges of migrating cells. The interactions with collagen may be a critical aspect of podocalyxin function. Podocalyxin is an important regulator of the EMT like process as it regulates the loss of epithelial features and the acquisition of a motile phenotype

Prevention of bone metastases and management of bone health in early breast cancer

Treatment options for women with early-stage breast cancer have never been better, and the addition of bisphosphonates to adjuvant therapy is a valuable new tool capable of substantially improving clinical outcomes for these women. Several recent studies demonstrated that the anticancer activity of bisphosphonates is not limited to bone, and can translate into a reduction in disease recurrence, including reductions in locoregional and distant metastases. In addition, bisphosphonates maintain bone health during adjuvant therapy; this may be especially important for women who are at high risk for fracture