Treatment of the painful neuroma by neuroma resection and muscle implantation

The successful treatment of the painful neuroma remains an elusive surgical goal. This report evaluates one approach to the management of this problem which entails neuroma excision and placement of the proximal end of the nerve away from denervated skin, away from tension, and into a well-vascularized environment: muscle. Seventy-eight neuromas in 60 patients with a mean follow-up of 31 months (range 18 to 43 months) were evaluated. Sixty-seven percent of these patients involved Workmen's Compensation and 57 percent had had at least one previous operation to treat their pain. The results demonstrated good to excellent results in 82 percent of the treated nerves in the entire group. Factors that were predictive of a poorer outcome were (1) digital neuroma (p less than 0.0005), (2) Workmen's Compensation (p less than 0.01), and (3) three or more previous operations for pain (p less than 0.01). Transposition of nerves into small superficial muscles or muscles with significant excursion resulted in treatment failures. The etiology and histopathology of treatment failures are reviewed. Treatment of radial sensory neuromas by transposition of the radial sensory nerve into the brachioradialis muscle when any associated injury to the lateral antebrachial cutaneous nerve was also treated, gave good to excellent relief of pain, and improved hand function in 88 percent of the patients.     

Electrophoretic migration of Paracoccidioides brasiliensis specific antigenic fraction

Using the technique of immunoelectroosmophoresisimmunodiffusion (IEOP-ID), two antigenic fractions of Paracoccidioides brasiliensis one of them species-specific, produced precipitin bands in both the cathodic and anodic zones. Reactions of complete identity among the bands formed in these zones were demonstrated by a modification of the technique, employing additional wells around the central antigen well. Such bands would correspond to a simple diffusion of the corresponding antigenic fractions rather than to active electrophoretic migration.

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Resumen Dos fracciones antigénicas de Paracoccidioides brasiliensis una de ellas presuntamente especifica, originan en la técnica de inmunoelectroosmoforesis-inmimodifusión (IEOF-ID), bandas de precipitación tanto en la región anódica como en la región catódica del preparado.Mediante simple procedimiento se demuestra reacción de identidad entre tales bandas cuyo origen correspondería a una difusión simple de las respectivas fracciones antigénicas sin movilidad electroforética activa.

     

Substrate Trapping Proteomics Reveals Targets of the βTrCP2/FBXW11 Ubiquitin Ligase

Defining the full complement of substrates for each ubiquitin ligase remains an important challenge. Improvements in mass spectrometry instrumentation and computation and in protein biochemistry methods have resulted in several new methods for ubiquitin ligase substrate identification. Here we used the parallel adapter capture (PAC) proteomics approach to study βTrCP2/FBXW11, a substrate adaptor for the SKP1–CUL1–F-box (SCF) E3 ubiquitin ligase complex. The processivity of the ubiquitylation reaction necessitates transient physical interactions between FBXW11 and its substrates, thus making biochemical purification of FBXW11-bound substrates difficult. Using the PAC-based approach, we inhibited the proteasome to “trap” ubiquitylated substrates on the SCF^FBXW11 E3 complex. Comparative mass spectrometry analysis of immunopurified FBXW11 protein complexes before and after proteasome inhibition revealed 21 known and 23 putatively novel substrates. In focused studies, we found that SCF^FBXW11 bound, polyubiquitylated, and destabilized RAPGEF2, a guanine nucleotide exchange factor that activates the small GTPase RAP1. High RAPGEF2 protein levels promoted cell-cell fusion and, consequently, multinucleation. Surprisingly, this occurred independently of the guanine nucleotide exchange factor (GEF) catalytic activity and of the presence of RAP1. Our data establish new functions for RAPGEF2 that may contribute to aneuploidy in cancer. More broadly, this report supports the continued use of substrate trapping proteomics to comprehensively define targets for E3 ubiquitin ligases. All proteomic data are available via ProteomeXchange with identifier PXD001062.     

Novel Pseudomonas Plasmid Involved in Aniline Degradation

Growth of the four methanogens investigated was inhibited by chloramphenicol-3-acetate; therefore, introduction of chloramphenicol acetyltransferase-encoding genes should not confer chloramphenicol resistance on these methanogens. Reduction of the aryl nitro group of chloramphenicol produced a compound which did not inhibit the growth of these methanogens.     

Revascularization of peripheral nerve autografts and allografts

The timing and mechanisms of peripheral nerve revascularization were investigated using a 2-cm sciatic nerve graft model in 58 rats. Epineurial perfusion was consistently established by 48 hours and endoneurial perfusion by 72 hours. The pattern of endoneurial perfusion was "all-or-none"--either all or none of the vessels in a fascicle exhibited blood flow. Conventional allografts exhibited similar revascularization dynamics and patterns. Capping the ends of the autograft with Silastic significantly delayed revascularization; no flow was observed at 4 days, and only a peripheral rim of perfused fascicular vessels was observed at 7 days. These patterns suggested that the primary method of revascularization in the conventional graft was longitudinal inosculation; no evidence of peripheral neovascularization or dependence on the graft bed as a source of revascularization was observed. The introduction of a major histocompatibility complex barrier between the grafted tissue and the recipient animal did not alter the timing or the mechanics of blood flow reestablishment.     

A predictive model for respiratory syncytial virus (RSV) hospitalisation of premature infants born at 33–35 weeks of gestational age,based on data from the Spanish FLIP study

Background

The aim of this study, conducted in Europe, was to develop a validated risk factor based model to predict RSV-related hospitalisation in premature infants born 33–35 weeks'' gestational age (GA).

Methods

The predictive model was developed using risk factors captured in the Spanish FLIP dataset, a case-control study of 183 premature infants born between 33–35 weeks'' GA who were hospitalised with RSV, and 371 age-matched controls. The model was validated internally by 100-fold bootstrapping. Discriminant function analysis was used to analyse combinations of risk factors to predict RSV hospitalisation. Successive models were chosen that had the highest probability for discriminating between hospitalised and non-hospitalised infants. Receiver operating characteristic (ROC) curves were plotted.

Results

An initial 15 variable model was produced with a discriminant function of 72% and an area under the ROC curve of 0.795. A step-wise reduction exercise, alongside recalculations of some variables, produced a final model consisting of 7 variables: birth ± 10 weeks of start of season, birth weight, breast feeding for ≤ 2 months, siblings ≥ 2 years, family members with atopy, family members with wheeze, and gender. The discrimination of this model was 71% and the area under the ROC curve was 0.791. At the 0.75 sensitivity intercept, the false positive fraction was 0.33. The 100-fold bootstrapping resulted in a mean discriminant function of 72% (standard deviation: 2.18) and a median area under the ROC curve of 0.785 (range: 0.768–0.790), indicating a good internal validation. The calculated NNT for intervention to treat all at risk patients with a 75% level of protection was 11.7 (95% confidence interval: 9.5–13.6).

Conclusion

A robust model based on seven risk factors was developed, which is able to predict which premature infants born between 33–35 weeks'' GA are at highest risk of hospitalisation from RSV. The model could be used to optimise prophylaxis with palivizumab across Europe.