Lateral ankle ligament anatomic reconstruction for chronic ankle instability: Allograft or autograft? A systematic review.

BACKGROUND: To investigate if there is any evidence in favour of autograft or allograft use for anatomic reconstruction of lateral ankle ligaments in patients with symptomatic chronic ankle instability. METHODS: A literature search was performed in PubMed MEDLINE, Cochrane Library, EMBASE and Google Scholar databases, over the years 1994-2017, to identify the studies presenting clinical results of anatomic lateral ankle ligaments reconstruction using various combinations of the keywords "lateral ankle ligaments reconstruction", "anatomic reconstruction", "chronic ankle instability", "allograft", "autograft". The surgical procedure was considered anatomic if consistent with the description of lateral ankle ligaments made by Burks and Morgan in 1994. RESULTS: Among the 89 papers matching the search terms, only 12 could be included in which 357 anatomic lateral ankle ligaments reconstructions were performed. One was a comparative case series (level of evidence III - LOE III) while other papers were retrospective case series (LOE IV), the mean Modified Coleman Methodology Score (MCMS) was fair: 56.7 (SD±5.2). Due to the low level of evidence of the available literature only a qualitative analysis was performed. The limited evidence from the studies analysed suggests that there is no difference in graft survivorship, graft-dependent variables, patient's satisfaction, clinical outcome measures and radiographic results between allograft and autograft. CONCLUSIONS: Given the low number of studies, their poor methodology score and their low level of evidence it is not possible to determine if allograft is better or safer than autograft. LEVEL OF EVIDENCE: Level IV, review paper of level III and level IV studies.

Distal Akin osteotomy for hallux valgus interphalangeus.

BACKGROUND: The aim of this study was to assess clinical and radiological outcomes in patients who underwent distal Akin osteotomy for hallux valgus interphalangeus (HVI). METHODS: A series of 15 consecutive patients (17 feet) was retrospectively reviewed. All the patients were preoperatively and post-operatively evaluated with a physical and radiographic assessment (HVI angle). Satisfaction has been assessed through a satisfaction survey, the scale used consisted in three possible choice: very satisfied, satisfied, not satisfied. RESULTS: Among 15 patients the 52.9% (9 patients) stated to be "very satisfied", the 41.2% (7 patients) "satisfied" and just a 5.9% (one patient) was "not satisfied". The mean HVI value decreased from 24.9°±7.8° preoperatively to 13.1°±5.8° postoperatively at last follow up (p<0.05). CONCLUSIONS: Based on these findings we can conclude that the distal Akin osteotomy can be considered safe and effective in the surgical correction of symptomatic HVI deformities.

Nerve growth factor derivative NGF61/100 promotes outgrowth of primary sensory neurons with reduced signs of nociceptive sensitization.

Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease. However, the development of an NGF-based therapy is limited by its potent pain activity. We have developed a "painless" derivative form of human NGF (NGF61/100), characterized by identical neurotrophic properties but a reduced nociceptive sensitization activity in vivo. Here we characterized the response of rat dorsal root ganglia neurons (DRG) to the NGF derivative NGF61/100, in comparison to that of control NGF (NGF61), analyzing the expression of noxious pro-nociceptive mediators. NGF61/100 displays a neurotrophic activity on DRG neurons comparable to that of control NGF61, despite a reduced activation of PLCγ, Akt and Erk1/2. NGF61/100 does not differ from NGF61 in its ability to up-regulate Substance P (SP) and Calcitonin Gene Related Peptide (CGRP) expression. However, upon Bradykinin (BK) stimulation, NGF61/100-treated DRG neurons release a much lower amount of SP and CGRP, compared to control NGF61 pre-treated neurons. This effect of painless NGF is explained by the reduced up-regulation of BK receptor 2 (B2R), respect to control NGF61. As a consequence, BK treatment reduced phosphorylation of the transient receptor channel subfamily V member 1 (TRPV1) in NGF61/100-treated cultures and induced a significantly lower intracellular Ca2+ mobilization, responsible for the lower release of noxious mediators. Transcriptomic analysis of DRG neurons treated with NGF61/100 or control NGF allowed identifying a small number of nociceptive-related genes that constitute an "NGF pain fingerprint", whose differential regulation by NGF61/100 provides a strong mechanistic basis for its selective reduced pain sensitizing actions.

ProNGF\NGF imbalance triggers learning and memory deficits, neurodegeneration and spontaneous epileptic-like discharges in transgenic mice.

ProNGF, the precursor of mature nerve growth factor (NGF), is the most abundant form of NGF in the brain. ProNGF and mature NGF differ significantly in their receptor interaction properties and in their bioactivity. ProNGF increases markedly in the cortex of Alzheimer's disease (AD) brains and proNGF\NGF imbalance has been postulated to play a role in neurodegeneration. However, a direct proof for a causal link between increased proNGF and AD neurodegeneration is lacking. In order to evaluate the consequences of increased levels of proNGF in the postnatal brain, transgenic mice expressing a furin cleavage-resistant form of proNGF, under the control of the neuron-specific mouse Thy1.2 promoter, were derived and characterized. Different transgenic lines displayed a phenotypic gradient of neurodegenerative severity features. We focused the analysis on the two lines TgproNGF#3 and TgproNGF#72, which shared learning and memory impairments in behavioral tests, cholinergic deficit and increased Aß-peptide immunoreactivity. In addition, TgproNGF#3 mice developed Aß oligomer immunoreactivity, as well as late diffuse astrocytosis. Both TgproNGF lines also display electrophysiological alterations related to spontaneous epileptic-like events. The results provide direct evidence that alterations in the proNGF/NGF balance in the adult brain can be an upstream driver of neurodegeneration, contributing to a circular loop linking alterations of proNGF/NGF equilibrium to excitatory/inhibitory synaptic imbalance and amyloid precursor protein (APP) dysmetabolism.

The Bologna-Oxford total ankle replacement: a mid-term follow-up study.

The Bologna-Oxford (BOX) total ankle replacement (TAR) was developed with the aim of achieving satisfactory pain-free movement of the ankle. To date, only one single multicentre study has reported its clinical results. The aim of this study was to conduct an independent review of its mid-term results. We retrospectively reviewed a total of 60 prospectively followed patients in whom 62 BOX TARs had been implanted between 2004 and 2008. We used the American Orthopedic Foot and Ankle Society (AOFAS) score to assess the clinical results. Standardised radiographs taken at the time of final follow-up were analysed by two observers. The overall survival was 91.9% at a mean follow-up of 42.5 months (24 to 71). The mean AOFAS score had improved from 35.1 points (sd 16.6; 4 to 73) pre-operatively to 78.0 (sd 10.7; 57 to 100) at final follow-up (p < 0.01). Tibial radiolucencies < 2 mm in width were seen around 16 TARs. Talar radiolucencies < 2 mm were seen around four TARs. A total of 47 patients (78.3%) were very satisfied or satisfied with the outcome. Five patients required revision for functional limitation or continuing pain.

A novel rapid scanning microspectrophotometer and its use in measuring rhodopsin photoproduct pathways and kinetics in frog retinas.

A novel rapid scanning microspectrophotometer is described which utilizes a cathode ray tube as a measuring light source. Spectral scanning is accomplished electronically with a sampling time of 600 mus for each waveband. The cathode ray tube emission is chopped electronically into two separate beams, 180 degrees out of phase, resulting in a dual-beam configuration. A lock-in amplifier functions as a coherent detector to recover separately the signals from the two beams. The instrument generates separate voltage outputs, one proportional to the transmittance of a single sample and the other to the difference between two samples. A computer calculates both absorption and difference spectra directly from voltage measurements. A demonstration of the instrument's use to study kinetics of visual pigment photoproducts is presented. Two models of photoproduct sequence and kinetics were examined to determine which better represents the experimental data. The experiments show that environmental factors, such as pH, metabolic and respiratory state, interact in complex ways to determine the pathways and kinetics of photoproducts of rhodopsin in intact vertebrate eyes.

Orientation and rotational freedom of fluorescent probes in lecithin bilayers.

The fluorescence polarization properties of lecithin bilayers stained with 2,6-MANS and 1,8 ANS under applied potential steps have been studied. The fluorescence signal components of both dyes were found to have different sign and relative amplitude, suggesting that 1,8-ANS and 2,6-MANS behave differently when bound to black lipid membranes. In order to determine the location and the extent of rotational brownian motions of the bound chromophores, the experimental data were analyzed by using a simplified physico-mathematical model. According to it 2,6-MANS appears to have a ratio rho/tau higher than 1.8-ANS (rho being the rotational relaxation of in plane rotations and tau the lifetime of the excited singlet state of the bound molecules), suggesting that the former chromophore is more tightly held inside the bilayers. Furthermore, 2,6-MANS is found to possess the absorption and emission oscillators more closely oriented to the normal of membrane surface, while 1,8-ANS has both oscillators almost near the plane of the bilayers. The results furnish also a fair estimate of the random molecular motion own by the phospholipid molecules at room temperature. The comparison of the present data with those obtained from squid axon membranes confirms the validity of the proposed physical model, yielding a rough estimate of the axon membrane-area covered by integral protein macromolecules. These preliminary results derived from lecithin model membranes suggest that fluorescence polarization techniques can provide valuable informations if applied to study the macromolecular organization of in vitro reconstituted membranes.