Biological resurfacing of the knee: a review of surgical management

Lesions of the articular surfaces of the knee have been managed by various techniques over the last 50 years. Surgical management has involved: excising the damaged area, refashioning the underlying bone to produce a fibrous response, and introducing allograft, autograft and synthetic materials to encourage a repair matrix. The techniques and their pitfalls are reviewed and discussed, and suggestions made as to the direction of future studies for the repair of osteochondral lesions in the painful knee.     

Postnatal outcome and placental blood flow after plasmapheresis during pregnancy

Purpose: Plasmapheresis in pregnancy adversely affects maternal hemodynamics, however there are studies suggesting it to reduce pregnancy loss in immunological diseases when medication is more harmful to the fetus. The overall optimal plasmapheresis treatment protocol remains unknown.

Materials and methods: A pregnant with neuromyelitis optica was followed up after receiving six volumes of fresh frozen plasma via plasmapheresis.

Results: The placenta compensated the hemodynamic change until the 33rd week of gestation, resulting a small for gestational age, otherwise healthy girl.

Conclusions: More research is needed on plasma exchange during pregnancy because in our observation placental circulation can adapt to the change in blood pressure.     

Placental volume relative to fetal weight estimated by sonography in diabetic pregnancies

Objective: Our purpose was to analyze the fetal weight and placental volume (PV) ratio in diabetic pregnancies during mid-pregnancy.

Method: One hundred and forty nine diabetic pregnancies [75 gestational diabetes mellitus (GDM) and 74 diabetes mellitus type I (T1DM) with good glycemic control] and 232 healthy patients were analyzed by three-dimensional sonographic volumetry of the placenta, while fetal weight was estimated by two-dimensional technique.

Results: The gestational age-specific estimated fetal weight (EFW) [EFWGDM: 1840.8?±?932.82?g; EFWT1DM: 1475.6?±?914.7?g (mean?±?standard deviation) and placental ratio (PR)] was significantly higher (p?<?0.05) in pregnancies complicated by GDM and T1DM (PRGDM: 5.5?±?1.67?g/cm³, PRT1DM: 4.56?±?3.2?g/cm³) compared to control group (Q) (EFWQ: 532?±?186.49?g; PRQ: 2.2?±?0.8?g/cm³), whereas PV was significantly higher (p?<?0.05) only in GDM (PVGDM: 334.3?±?111.5?cm³) compared to control data (PVQ: 232?±?78.9?cm³). In contrast to GDM, T1DM with good glycemic control did not predispose to any changes in placental sonographic volumetric differences compared to control values.

Conclusions: Fetal weight related to the PV is already elevated in second trimester in pregnancies complicated by gestational diabetes mellitus and type I diabetes mellitus compared to normal pregnancies.     

Mutation of E1 glycoprotein of classical swine fever virus affects viral virulence in swine

Transposon linker insertion mutagenesis of a full-length infectious clone (IC) (pBIC) of the pathogenic classical swine fever virus (CSFV) strain Brescia was used to identify genetic determinants of CSFV virulence and host range. Here, we characterize a virus mutant, RB-C22v, possessing a 19-residue insertion at the carboxyl terminus of E1 glycoprotein. Although RB-C22v exhibited normal growth characteristics in primary porcine macrophage cell cultures, the major target cell of CSFV in vivo, it was markedly attenuated in swine. All RB-C22v-infected pigs survived infection remaining clinically normal in contrast to the 100% mortality observed for BICv-infected animals. Comparative pathogenesis studies demonstrated a delay in RB-C22v spread to, and decreased replication in the tonsils, a 10(2) to 10(7) log10 reduction in virus titers in lymphoid tissues and blood, and an overall delay in generalization of infection relative to BICv. Notably, RB-C22v-infected animals were protected from clinical disease when challenged with pathogenic BICv at 3, 5, 7, and 21 days post-RB-C22v inoculation. Viremia, viral replication in tissues, and oronasal shedding were reduced in animals challenged at 7 and 21 DPI. Notably BICv-specific RNA was not detected in tonsils of challenged animals. These results indicate that a carboxyl-terminal domain of E1 glycoprotein affects virulence of CSFV in swine, and they demonstrate that mutation of this domain provides the basis for a rationally designed and efficacious live-attenuated CSF vaccine.     

Self-assembling glucagon-like peptide 1-mimetic peptide amphiphiles for enhanced activity and proliferation of insulin-secreting cells

Current treatment for type 1 diabetes mellitus requires daily insulin injections that fail to produce physiological glycemic control. Islet cell transplantation has been proposed as a permanent cure but is limited by loss of β-cell viability and function. These limitations could potentially be overcome by relying on the activity of glucagon-like peptide 1 (GLP-1), which acts on β-cells to promote insulin release, proliferation and survival. We have developed a peptide amphiphile (PA) molecule incorporating a peptide mimetic for GLP-1. This GLP-1-mimetic PA self-assembles into one-dimensional nanofibers that stabilize the active secondary structure of GLP-1 and can be cross-linked by calcium ions to form a macroscopic gel capable of cell encapsulation and three-dimensional culture. The GLP-1-mimetic PA nanofibers were found to stimulate insulin secretion from rat insulinoma (RINm5f) cells to a significantly greater extent than the mimetic peptide alone and to a level equivalent to that of the clinically used agonist exendin-4. The activity of the GLP-1-mimetic PA is glucose-dependent, lipid-raft dependent and partially PKA-dependent consistent with native GLP-1. The GLP-1-mimetic PA also completely abrogates inflammatory cytokine-induced cell death to the level of untreated controls. When used as a PA gel to encapsulate RINm5f cells, the GLP-1-mimetic PA stimulates insulin secretion and proliferation in a cytokine-resistant manner that is significantly greater than a non-bioactive PA gel containing exendin-4. Due to its self-assembling property and bioactivity, the GLP-1-mimetic PA can be incorporated into previously developed islet cell transplantation protocols with the potential for significant enhancement of β-cell viability and function.     

Copy number profiling in von Hippel-Lindau disease renal cell carcinoma

Germline mutations in the VHL tumor suppressor gene cause von Hippel-Lindau (VHL) disease and somatic VHL mutations occur in the majority of clear cell renal cell carcinoma (cRCC). To compare copy number abnormalities (CNAs) between cRCC from VHL patients and sporadic cRCC cases without detectable somatic VHL mutations, we analyzed 34 cRCC with Affymetrix 250K arrays. To increase the power of the study, we then combined our results with those of a previously published study and compared CNAs in VHL and non-VHL related cRCC using the genomic identification of significant targets in cancer (GISTIC) program. In VHL, cRCC GISTIC analysis identified four statistically significant regions of copy number gain and four statistically significant regions of deletion that occurred in >10% of tumors analyzed. Sporadic cRCC without detectable VHL mutations had, on average, more copy number abnormalities than VHL cRCC though the most common regions of loss/gain (e.g., 3p and 14q loss and 5q gain) were present in both tumor sets. However, CNAs on chromosome arms 7p (gain) and 8p (loss) were only detected in VHL RCC. Although individual copy number abnormality peaks contained clear candidate cancer genes in some cases (e.g., the 3p loss peak in VHL cRCC contained only six genes including VHL), most peaks contained many genes. To date, only a minority of the candidate genes included in these peaks have been analyzed for mutation or epigenetic inactivation in cRCC but TNFRSF10C and DUSP4 map to the 8p region deleted in VHL cRCC and TP53 and HIF2A (EPAS1) mapped to CNA loss and gain peaks (chromosomes 17 and 2, respectively) detected in sporadic VHL wild-type cRCC.     

Dynamic properties of recurrent inhibition in primary visual cortex: contrast and orientation dependence of contextual effects

A fundamental feature of neural circuitry in the primary visual cortex (V1) is the existence of recurrent excitatory connections between spiny neurons, recurrent inhibitory connections between smooth neurons, and local connections between excitatory and inhibitory neurons. We modeled the dynamic behavior of intermixed excitatory and inhibitory populations of cells in V1 that receive input from the classical receptive field (the receptive field center) through feedforward thalamocortical afferents, as well as input from outside the classical receptive field (the receptive field surround) via long-range intracortical connections. A counterintuitive result is that the response of oriented cells can be facilitated beyond optimal levels when the surround stimulus is cross-oriented with respect to the center and suppressed when the surround stimulus is iso-oriented. This effect is primarily due to changes in recurrent inhibition within a local circuit. Cross-oriented surround stimulation leads to a reduction of presynaptic inhibition and a supraoptimal response, whereas iso-oriented surround stimulation has the opposite effect. This mechanism is used to explain the orientation and contrast dependence of contextual interactions in primary visual cortex: responses to a center stimulus can be both strongly suppressed and supraoptimally facilitated as a function of surround orientation, and these effects diminish as stimulus contrast decreases.     

Dynamics of neuronal sensitivity in visual cortex and local feature discrimination

A striking aspect of natural scenes is that image features such as line orientation are strongly correlated at neighboring spatial locations but not at distant locations. Thus, during the viewing of a scene, eye movements are often accompanied by a change in the orientation structure of the image. How does this behavior influence the discrimination of local features and their encoding by visual cortical neurons? Here we examined the perceived changes in orientation induced by brief exposure to oriented image patterns in monkeys and humans, and then used reverse correlation to investigate dynamic changes in neuronal sensitivity in the primary visual cortex (V1) of behaving monkeys. Whereas brief adaptation to an oriented grating impaired identification of nearby orientations by broadening orientation selectivity and changing the preferred orientation of individual V1 neurons, it actually enhanced the identification of orthogonal orientations by sharpening neuronal selectivity. Hence, successive exposure to image patches of dissimilar spatial structure enhances both the ability to discriminate local features and the encoding of these features by V1 neurons.     

Brain responses to stimuli mimicking dental treatment among non‐phobic individuals: A meta‐analysis

Numerous neuroimaging studies have attempted to identify how the brain responds to stimuli mimicking dental treatment in normal non‐phobic individuals. However, results were sometimes inconsistent due to small sample sizes and methodological variations. This meta‐analysis employs standardized procedures to summarize data from previous studies to identify brain regions that were consistently activated across studies, elicited by stimuli such as pictures, sounds, or audiovisual footage mimicking those encountered during dental treatments. A systematic literature search was carried out using PubMed and Scopus. The meta‐analysis analyzed data from 120 healthy subjects from seven neuroimaging studies. We assessed the risk of bias among the included studies with the Risk of Bias Assessment Tool for Nonrandomized Studies. One study appeared to have a high risk of selection bias, whereas the others were considered to have a low risk of bias. Results revealed three clusters of activation with cluster sizes ranging from 768 mm³ to 1,424 mm³. Stimuli mimicking dental treatment consistently activated the bilateral anterior insula; right dorsal anterior cingulate, putamen, and medial prefrontal cortex; and left claustrum. This study confirmed that audio and/or visual stimuli mimicking dental treatment consistently activated the fear‐related brain regions among healthy subjects, mostly consistent with activations from general anxiety but without the involvement of the amygdala.