MIS Distal Metatarsal Metaphyseal Osteotomy in the treatment of metatarsalgia: MOXFQ patient reported outcomes.

INTRODUCTION: The aim of this paper is to present validated patient reported outcomes for MIS Distal Metatarsal Metaphyseal Osteotomy (DMMO) in the treatment of metatarsalgia. The study aims to evaluate the DMMO procedure, report patient satisfaction with the operated foot and report any complications of this procedure. PATIENTS AND METHODS: Between 2014 and 2016, patients who had failed conservative treatment for metatarsalgia were identified in the orthopaedic outpatient clinic. Twenty four consecutive patients requiring DMMO plus/minus toe straightening were prospectively studied. Patients requiring additional procedures at the time of surgery were excluded. Patients completed the validated Manchester-Oxford Foot Questionnaire (MOXFQ) three weeks pre-operatively and 1 year postoperatively. The MOXFQ results were analysed using Paired t-tests. A supplementary question was asked regarding patient satisfaction with the operated foot. RESULTS: There were 20 women and 4 men with a mean age of 64 years (sd 8.6). Statistically significant differences were found between the pre and postoperative MOXFQ. The postoperative MOXFQ score demonstrated a poorer result for two patients, no change for two patients and improvement in 20 patients, with four of these patients recording the lowest possible score. There was a 29.5 point improvement in mean metric MOXFQ Index score. Seventy-nine percent (n = 19) of patients were satisfied or very satisfied with the operated foot. The average recoil of the metatarsal heads following DMMO was M2 4.01 mm, M3 4.55 mm, M4 4.16 mm. There was one delayed union and no non-unions. Further reported complications were a gastric bleed, pulmonary embolism (VTE), and one intra operative broken burr. CONCLUSION: Our study demonstrates a clinically important and statistically significant improvement in patient reported outcomes following DMMO, with 79% of patients satisfied or very satisfied with this procedure. The average recoil of the metatarsal heads following DMMO was M2 4.01 mm, M3 4.55 mm, M4 4.16 mm with one delayed union and no non-unions.

UNC13A polymorphism contributes to frontotemporal disease in sporadic amyotrophic lateral sclerosis.

The majority (90%-95%) of amyotrophic lateral sclerosis (ALS) is sporadic, and ∼50% of patients develop symptoms of frontotemporal degeneration (FTD) associated with shorter survival. The genetic polymorphism rs12608932 in UNC13A confers increased risk of sporadic ALS and sporadic FTD and modifies survival in ALS. Here, we evaluate whether rs12608932 is also associated with frontotemporal disease in sporadic ALS. We identified reduced cortical thickness in sporadic ALS with T1-weighted magnetic resonance imaging (N = 109) relative to controls (N = 113), and observed that minor allele (C) carriers exhibited greater reduction of cortical thickness in the dorsal prefrontal, ventromedial prefrontal, anterior temporal, and middle temporal cortices and worse performance on a frontal lobe-mediated cognitive test (reverse digit span). In sporadic ALS with autopsy data (N = 102), minor allele homozygotes exhibited greater burden of phosphorylated tar DNA-binding protein-43 kda (TDP-43) pathology in the middle frontal, middle temporal, and motor cortices. Our findings demonstrate converging evidence that rs12608932 may modify frontotemporal disease in sporadic ALS and suggest that rs12608932 may function as a prognostic indicator and could be used to define patient endophenotypes in clinical trials.

Expansion of the classification of FTLD-TDP: distinct pathology associated with rapidly progressive frontotemporal degeneration.

Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) can typically be categorized into one of four distinct histopathologic patterns of TDP-43 pathology, types A to D. The strength of this histopathologic classification lies in the association between FTLD-TDP subtypes and various clinical and genetic features of disease. Seven cases of FTLD-TDP were identified here which were difficult to classify based on existing pathologic criteria. Distinct features common to these cases included TDP-43 aggregates over a wide neuroanatomic distribution comprised of granulofilamentous neuronal inclusions, abundant grains, and oligodendroglial inclusions. TDP-43 aggregates were phosphorylated and associated with loss of normal nuclear TDP-43 protein (nuclear clearance) but were negative for ubiquitin. Biochemical analysis confirmed the presence of insoluble and phosphorylated TDP-43 and also revealed a distinct pattern of TDP-43 C-terminal fragments relative to other FTLD-TDP subtypes. Finally, these cases were uniformly associated with a very rapid clinical course culminating in death within ~3 years of disease onset. We suggest that these cases may represent a unique clinicopathologic subtype of FTLD-TDP which we provisionally call "type E." The immature appearance of TDP-43 aggregates, widespread distribution, uniform biochemical profile and rapid clinical course highlights the clinical and pathologic variability within FTLD-TDP, and raises the possibility that type E neuropathology is the sequelae of a particularly virulent strain of TDP-43 proteinopathy.

Analysis of cellulose synthase gene expression strategies in higher plants using RNA-sequencing data.

The transcriptomes from different organs and tissues of western poplar, eucalyptus, soybean and common bean were studied. The expression level of cellulose synthase genes was notably different in different types of tissues and organs in studied plants. For common bean and eucalyptus transcriptome the domination of certain cellulose synthase genes was typical. These prevailing genes made up more than 50 % of the total expression pull of cellulose synthases. On the contrary, cellulose synthase expression pulls of wes-tern poplar and soybean were distributed between multiple genes. The different expression strategies of CesA-genes may reflect a phylogenetic processes that occurred in genomes studied.

[Obtaining the transgenic lines of finger millet Eleusine coracana (L.) Gaertn. With dinitroaniline resistance].

The current data is dedicated to the study of bioballistic and Agrobacterium-mediated transformation of finger millet with the constructs carrying the mutant alpha-tubulin gene (TUAm 1), isolated from R-biotype goosegrass (Eleusine indica L.), for the decision of problem of dinitroaniline-resistance. It was found that 10 microM of trifluralin is optimal for the selection of transgene plants of finger millet. PCR analysis of transformed lines confirmed the transgene nature of plants. The analysis of seed of T1 oftransgene lines confirmed heterozygous character of inheritance of the resistance.

[Genetic transformation of flax (Linum usitatissimum L.) with chimeric GFP-TUA6 gene for visualisation of microtubules].

The data of Agrobacterium-mediated transformation of some Linum usitatissimum cultivars zoned on the territories of Belarus and Ukraine with the plasmid carrying chimeric GFP-TUA6 gene and nptII gene as selectable marker conferring resistance to kanamycin are presented in this study. Transformation was affected by a number of factors including optical density (OD600), time of inoculation of explants with Agrobacterium and co-culture conditions. Transgenic nature of obtained lines was confirmed by PCR analysis. Expression of GFP-TUA6 gene was detected with confocal laser scanning microscopy. The obtained transgenic lines can be used for further functional studies the role of microtubules in the processes of building the flax fibres and resistance to wind.

Analysis of C. elegans NR2E nuclear receptors defines three conserved clades and ligand-independent functions.

BACKGROUND: The nuclear receptors (NRs) are an important class of transcription factors that are conserved across animal phyla. Canonical NRs consist of a DNA-binding domain (DBD) and ligand-binding domain (LBD). While most animals have 20-40 NRs, nematodes of the genus Caenorhabditis have experienced a spectacular proliferation and divergence of NR genes. The LBDs of evolutionarily-conserved Caenorhabditis NRs have diverged sharply from their Drosophila and vertebrate orthologs, while the DBDs have been strongly conserved. The NR2E family of NRs play critical roles in development, especially in the nervous system. In this study, we explore the phylogenetics and function of the NR2E family of Caenorhabditis elegans, using an in vivo assay to test LBD function. RESULTS: Phylogenetic analysis reveals that the NR2E family of NRs consists of three broadly-conserved clades of orthologous NRs. In C. elegans, these clades are defined by nhr-67, fax-1 and nhr-239. The vertebrate orthologs of nhr-67 and fax-1 are Tlx and PNR, respectively. While the nhr-239 clade includes orthologs in insects (Hr83), an echinoderm, and a hemichordate, the gene appears to have been lost from vertebrate lineages. The C. elegans and C. briggsae nhr-239 genes have an apparently-truncated and highly-diverged LBD region. An additional C. elegans NR2E gene, nhr-111, appears to be a recently-evolved paralog of fax-1; it is present in C. elegans, but not C. briggsae or other animals with completely-sequenced genomes. Analysis of the relatively unstudied nhr-111 and nhr-239 genes demonstrates that they are both expressed--nhr-111 very broadly and nhr-239 in a small subset of neurons. Analysis of the FAX-1 LBD in an in vivo assay revealed that it is not required for at least some developmental functions. CONCLUSIONS: Our analysis supports three conserved clades of NR2E receptors, only two of which are represented in vertebrates, indicating three ancestral NR2E genes in the urbilateria. The lack of a requirement for a FAX-1 LBD suggests that the relatively high level of sequence divergence for Caenorhabditis LBDs reflects relaxed selection on the primary sequence as opposed to divergent positive selection. This observation is consistent with a model in which divergence of some Caenorhabditis LBDs is allowed, at least in part, by the absence of a ligand requirement.

The tailless ortholog nhr-67 functions in the development of the C. elegans ventral uterus.

The development of the C. elegans uterus provides a model for understanding the regulatory pathways that control organogenesis. In C. elegans, the ventral uterus develops through coordinated signaling between the uterine anchor cell (AC) and a ventral uterine (VU) cell. The nhr-67 gene encodes the nematode ortholog of the tailless nuclear receptor gene. Fly and vertebrate tailless genes function in neuronal and ectodermal developmental pathways. We show that nhr-67 functions in multiple steps in the development of the C. elegans uterus. First, it functions in the differentiation of the AC. Second, it functions in reciprocal signaling between the AC and an equipotent VU cell. Third, it is required for a later signaling event between the AC and VU descendants. nhr-67 is required for the expression of both the lag-2/Delta signal in the AC and the lin-12/Notch receptor in all three VU cells and their descendants, suggesting that nhr-67 may be a key regulator of Notch-signaling components. We discuss the implications of these findings for proposed developmental regulatory pathways that include the helix-loop-helix regulator hlh-2/daughterless and transcription factor egl-43/Evi1 in the differentiation of ventral uterine cell types.

The occurrence of rabies in pre-Columbian Central America: an historical search.

Rabies is considered one of the oldest infectious diseases known to humans. However, the first written reports on rabies cases in the Americas did not appear until the first decade of the 18th century from Mexico. In an attempt to clarify if the disease was already present in pre-Columbian times, we searched for evidence in the Maya and Aztec cultures. Other sources of information were early manuscripts written by the conquistadors and early explorers. We did not identify any unequivocal direct evidence that the disease rabies was known in pre-Columbian Central America but sufficient circumstantial evidence is available suggesting that (bat) rabies was already present in these early times.

Model simulation and experimental verification of a cation-exchange IgG capture step in batch and continuous chromatography.

The cation-exchange capture step of a monoclonal antibody (mAb) purification process using single column batch and multicolumn continuous chromatography (MCSGP) was modeled with a lumped kinetic model. Model parameters were experimentally determined under analytical and preparative conditions: porosities, retention factors and mass transfer parameters of purified mAb were obtained through a systematic procedure based on retention time measurements. The saturation capacity was determined through peak fitting assuming a Langmuir-type adsorption isotherm. The model was validated using linear batch gradient elutions. In addition, the model was used to simulate the start-up, cyclic steady state and shut down behavior of the continuous capture process (MCSGP) and to predict performance parameters. The obtained results were validated by comparison with suitable experiments using an industrial cell culture supernatant. Although the model was not capable of delivering quantitative information of the product purity, it proved high accuracy in the prediction of product concentrations and yield with an error of less than 6%, making it a very useful tool in process development.

Two step capture and purification of IgG2 using multicolumn countercurrent solvent gradient purification (MCSGP).

A two-step chromatography process for monoclonal antibody (mAb) purification from clarified cell culture supernatant (cCCS) was developed using cation exchange Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) as a capture step. After an initial characterization of the cell culture supernatant the capture step was designed from a batch gradient elution chromatogram. A variety of chromatographic materials was screened for polishing of the MCSGP-captured material in batch mode. Using multi-modal anion exchange in bind-elute mode, mAb was produced consistently within the purity specification. The benchmark was a state-of-the-art 3-step chromatographic process based on protein A, anion and cation exchange stationary phases. The performance of the developed 2-step process was compared to this process in terms of purity, yield, productivity and buffer consumption. Finally, the potential of the MCSGP process was investigated by comparing its performance to that of a classical batch process that used the same stationary phase.

Rabies control in Mexico.

Rabies in dogs was unknown in the Americas before the arrival of the Spanish "Conquistadores". Until the mid-1980s rabies in animals and, in turn in humans, changed little from year to year, with the number of dog vaccinations reported annually rarely reaching one million. In Mexico, the national rabies control programme using mass parenteral vaccination of dogs started in 1990 with about seven million dogs vaccinated the same year. The number of vaccinated dogs exceeded 10 and 15 million in 1995 and 2005, respectively. Modern cell culture-based inactivated rabies virus vaccines were used. A key factor for the success of the dog rabies control program was the supply of potent canine rabies vaccines. Between 1990 and 2005, more than 150 million vaccine doses from 300 lots were administered. Each lot was tested for potency prior to use in the field. The required minimum content of rabies virus antigen for vaccines was 2 IU, in accord with WHO standards. Testing revealed antigen contents ranging from 3.28 to 5.59 IU. As a result of the mass dog vaccination campaigns, human rabies cases due to dog-mediated rabies decreased from 60 in 1990 to 0 in 2000. The number of rabies cases in dogs decreased from 3,049 in 1990 to 70 cases last year.

Mechanical ventilation or phrenic nerve stimulation for treatment of spinal cord injury-induced respiratory insufficiency.

STUDY DESIGN: Prospective clinical study of two treatments. OBJECTIVE: To compare mechanical ventilation (MV) with phrenic nerve stimulation (PNS) for treatment of respiratory device-dependent (RDD) spinal cord-injured (SCI) patients. SETTING: Department for spinal cord-injured patients of an insurance-company-run trauma hospital in Hamburg, Germany. METHODS: Prospective data collection of treatment-related data over 20 years. RESULTS: In total, 64 SCI-RDD patients were treated during the study period. Of these, 32 of the patients with functioning phrenic nerves and diaphragm muscles were treated with PNS and 32 patients with destroyed phrenic nerves were mechanically ventilated. Incidence of respiratory infections (RIs per 100 days) prior to use of final respiratory device was equal in both groups, that is (median (interquartile range)) 1.43 (0.05-3.92) with PNS and 1.33 (0.89-2.21) with MV (P=0.888); with final device in our institution it was 0 (0-0.92) with PNS and 2.07 (1.49-4.19) with MV (P<0.001); at final location it was 0 (0-0.02) with PNS and 0.14 (0-0.31) with MV (P<0.001). Thus, compared to MV, respiratory treatment with PNS significantly reduces frequency of RI. Quality of speech is significantly better with PNS. Nine patients with PNS, but only two with MV, were employed or learned after rehabilitation (P=0.093). The primary investment in the respiratory device is higher with PNS, but it can be paid off in our setting within 1 year because of the reduced amount of single use equipment, easier nursing and fewer RIs compared to MV. CONCLUSIONS: PNS instead of MV for treatment of SCI-RDD reduces RIs, running costs of respiratory treatment and obviously improves patients' quality of life.

Burst suppression during propofol anaesthesia recorded from scalp and subthalamic electrodes: report of three cases.

BACKGROUND: Measurement of slow EEG activity and burst suppression are the main tasks in monitoring the effects of anaesthestics with EEG, which is often done with commercial univariate indexes such as BIS. The aim of this study was to describe the characteristics of burst suppression EEG during propofol anaesthesia using scalp electrodes and depth electrodes in the subthalamic nucleus. Specifically, we describe the electrical fields of the three EEG patterns we have previously described: the sharp wave, the burst and the spindle. METHODS: We recorded the EEG of three Parkinson patients during propofol anaesthesia from the scalp electrodes and the depth electrode implanted in the subthalamic nucleus for treating parkinsonism. RESULTS: (1) The slow waves of bursts recorded from all surface electrodes on scalp or neck with depth electrode reference are positive and have the highest amplitude in frontal electrodes, suggesting synchronous generation in the whole cerebral cortex. (2) The sharp wave and spindles have the highest amplitude at vertex. They are opposite in polarity in vertex and depth electrodes when referred to the neck electrode, suggesting generation in the sensorimotor cortex. CONCLUSIONS: Recording simultaneously EEG from the depth and scalp electrodes shows that bursts and their slow wave oscillations are synchronous in the whole cortex while spindles and sharp waves are produced by the sensorimotor cortex. The amplitude of slow waves recorded with surface electrodes is equal to the difference of the wave at two electrodes and therefore only a small part of that generated by the cortex.

[Somaclonal variability as a source for creation of new varieties of finger millet Eleusine coracana (L.) Gaertn].

Data on selection and characterizing of finger millet Eleusine coracana (L.) Gaertn. somaclonal variants regenerated from callus culture are presented and described. Among the tested genetically stable lines the somaclonal variant SE-7 was the most interesting due to its acquired important agricultural traits, such as a higher seed and biomass yield, rapid seed germination at lower temperatures, shortening of the main plant development stages. Data analysis shows that somaclonal variability can be a source to obtain initial material for further selection of new finger millet varieties.

Physiotherapy treatment approaches for the recovery of postural control and lower limb function following stroke.

BACKGROUND: There are a number of different approaches to physiotherapy treatment following stroke that, broadly speaking, are based on neurophysiological, motor learning and orthopaedic principles. Some physiotherapists base their treatment on a single approach, while others use a mixture of components from a number of different approaches. OBJECTIVES: To determine if there is a difference in the recovery of postural control and lower limb function in patients with stroke if physiotherapy treatment is based on orthopaedic or neurophysiological or motor learning principles, or on a mixture of these treatment principles. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched May 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to May 2005), EMBASE (1980 to May 2005) and CINAHL (1982 to May 2005). We contacted experts and researchers with an interest in stroke rehabilitation. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of physiotherapy treatment approaches aimed at promoting the recovery of postural control and lower limb function in adult participants with a clinical diagnosis of stroke. Outcomes included measures of disability, motor impairment or participation. DATA COLLECTION AND ANALYSIS: Two review authors independently categorised the identified trials according to the inclusion and exclusion criteria, documented their methodological quality, and extracted the data. MAIN RESULTS: Twenty-one trials were included in the review, five of which were included in two comparisons. Eight trials compared a neurophysiological approach with another approach; eight compared a motor learning approach with another approach; and eight compared a mixed approach with another approach. A mixed approach was significantly more effective than no treatment or placebo control for improving functional independence (standardised mean difference (SMD) 0.94, 95% confidence intervals (CI) 0.08 to 1.80). There was no significant evidence that any single approach had a better outcome than any other single approach or no treatment control. AUTHORS' CONCLUSIONS: There is evidence that physiotherapy intervention, using a mix of components from different approaches, is significantly more effective than no treatment or placebo control in the recovery of functional independence following stroke. There is insufficient evidence to conclude that any one physiotherapy approach is more effective in promoting recovery of lower limb function or postural control following stroke than any other approach. We recommend that future research should concentrate on investigating the effectiveness of clearly described individual techniques and task-specific treatments, regardless of their historical or philsophical origin.

How we do it: regular infusion of local anaesthetic in the pedicle of pectoralis major myocutaneous flap to shorten hospitalization of surgically treated head and neck cancer patients.

Keypoints *Regular infusion of the flap with local anaesthetic for 6 days postoperative via an indwelling catheter is easy. *It does not cause any complications. *It shortens hospitalization by 7 days. *The necessary catheter is readily available.

Requirements of propofol at different end-points without adjuvant and during two different steady infusions of remifentanil.

BACKGROUND: Some reports show no interaction between propofol and opioids, whereas others state such interactions. We evaluated the influence of remifentanil on propofol requirements at certain anesthesia end-points. METHODS: Elective surgical patients were randomly assigned to three groups of 15 patients each. Premedication was with oral diazepam 0.1 mg kg(-1). Patients were blindly given equal volumes of saline or remifentanil (7.5 or 30 microg kg(-1). h(-1)) 1 min before induction of anesthesia with infusion of propofol, 30 mg kg(-1). h(-1). We recorded times to, propofol requirements, and bispectral index at loss of counting (LC), loss of verbal command (LVC), loss of reaction to tetanic stimulation (LRT), and onset of burst suppression pattern (BSP) of electroencephalography. RESULTS: In the remifentanil groups end-points were attained significantly faster and with lower doses of propofol than in the saline group. BIS-values were significantly different at LRT and BSP end-points. CONCLUSIONS: We conclude that remifentanil infusion started before induction of propofol anesthesia significantly reduces propofol requirements at all end-points. The results suggest that remifentanil accelerates the hypnotic onset of propofol.