The shape of dendritic arbors in different functional domains of the cortical orientation map.

The neocortex is organized into macroscopic functional maps. However, at the microscopic scale, the functional preference and degree of feature selectivity between neighboring neurons can vary considerably. In the primary visual cortex, adjacent neurons in iso-orientation domains share the same orientation preference, whereas neighboring neurons near pinwheel centers are tuned to different stimulus orientations. Moreover, several studies have found greater orientation selectivity in iso-orientation domains than in pinwheel centers. These differences suggest that neurons sample local inputs in a spatially homogenous fashion and independently of the location of their soma on the orientation map. Here we determine whether dendritic geometry is affected by neuronal position on the orientation map. We labeled individual layer 2/3 pyramidal neurons with fluorescent dyes in specific domains of the orientation map in cat primary visual cortex and imaged their dendritic trees in vivo by two-photon microscopy. We found that the circularity and uniformity of dendritic trees is independent of somatic position on the orientation map. Moreover, the dendrites of neurons located close to pinwheel centers extend across all orientation domains in an unbiased fashion. Thus, unbiased dendritic trees appear to provide an anatomical substrate for the systematic variations in feature selectivity across the orientation map.

Regenerative potential of decellularized porcine nucleus pulposus hydrogel scaffolds: stem cell differentiation, matrix remodeling, and biocompatibility studies.

Nucleus pulposus (NP) tissue regeneration has been proposed as an early stage interventional therapy to combat intervertebral disc degeneration. We have previously reported on the development and characterization of a novel biomimetic acellular porcine NP (APNP) hydrogel. Herein, we aimed to evaluate this material for use as a suitable scaffold for NP tissue regeneration. Human-adipose-derived stem cells (hADSCs) were cultured for 14 days on APNP hydrogels in chemically defined differentiation media and were analyzed for an NP-cell-like mRNA expression profile, evidence of hydrogel remodeling including hydrogel contraction measurements, extracellular matrix production, and compressive dynamic mechanical properties. The innate capacity of the hydrogel itself to induce stem cell differentiation was also examined via culture in media lacking soluble differentiation factors. Additionally, the in vivo biocompatibility of non-crosslinked and ethyldimethylaminopropyl carbodiimide/N-hydroxysuccinimide and pentagalloyl glucose crosslinked hydrogels was evaluated in a rat subdermal model. Results indicated that hADSCs expressed putative NP-cell-positive gene transcript markers when cultured on APNP hydrogels. Additionally, glycosaminoglycan and collagen content of hADSC-seeded hydrogels was significantly greater than nonseeded controls and cell-seeded hydrogels exhibited evidence of contraction and tissue inhibitors of metalloproteinase-1 production. The dynamic mechanical properties of the hADSC-seeded hydrogels increased with time in culture in comparison to noncell-seeded controls and approached values reported for native NP tissue. Immunohistochemical analysis of explants illustrated the presence of mononuclear cells, including macrophages and fibroblasts, as well as blood vessel infiltration and collagen deposition within the implant interstices after 4 weeks of implantation. Taken together, these results suggest that APNP hydrogels, in concert with autologous ADSCs, may serve as a suitable scaffold for NP tissue regeneration.

Early warning indicators for HIV drug resistance in Cameroon during the year 2010.

BACKGROUND: Rapid scale-up of antiretroviral therapy (ART) in resource-limited settings is accompanied with an increasing risk of HIV drug resistance (HIVDR), which in turn could compromise the performance of national ART rollout programme. In order to sustain the effectiveness of ART in a resource-limited country like Cameroon, HIVDR early warning indicators (EWI) may provide relevant corrective measures to support the control and therapeutic management of AIDS. METHODS: A retrospective study was conducted in 2010 among 40 ART sites (12 Approved Treatment Centers and 28 Management Units) distributed over the 10 regions of Cameroon. Five standardized EWIs were selected for the evaluation using data from January through December, among which: (1) Good ARV prescribing practices: target = 100%; (2) Patient lost to follow-up: target ≤ 20%; (3) Patient retention on first line ART: target ≥ 70%; (4) On-time drug pick-up: target ≥ 90%; (5) ARV drug supply continuity: target = 100%. Analysis was performed using a Data Quality Assessment tool, following WHO protocol. RESULTS: THE NUMBER OF SITES ATTAINING THE REQUIRED PERFORMANCE ARE: 90% (36/40) for EWI(1), 20% (8/40) for EWI(2); 20% (8/40) for EWI(3); 0% (0/37) for EWI(4); and 45% (17/38) for EWI 5. ARV prescribing practices were in conformity with the national guidelines in almost all the sites, whereas patient adherence to ART (EWI(2), EWI(3), and EWI(4)) was very low. A high rate of patients was lost-to-follow-up and others failing first line ART before 12 months of initiation. Discontinuity in drug supply observed in about half of the sites may negatively impact ARV prescription and patient adherence. These poor ART performances may also be due to low number of trained staff and community disengagement. CONCLUSIONS: The poor performance of the national ART programme, due to patient non-adherence and drug stock outs, requires corrective measures to limit risks of HIVDR emergence in Cameroon.