Conservative Treatment for Primary Metatarsalgia

Metatarsalgia is one of the most common causes of forefoot pain, and it is characterized by pain in the front part of the foot under the head of the metatarsal bones. Primary metatarsalgia is idiopathic, but it has been suggested to be related to forefoot plantar compression. Because of the various causes of metatarsalgia, there is the need to thoroughly consider the etiology of metatarsalgia to find novel, effective, and conservative treatments for metatarsalgia to avoid surgical treatment. Pressure reduction or redistribution can be achieved using toe exercise, flat shoe inserts, metatarsal pads, custom-molded inserts, and rockerbars. There was no need for one treatment. If toe function was poor, toe exercises were recommended. If dorsiflexion of the ankle joint was limited, the Achilles tendon was stretched. If the pain was localized to the plantar aspect of the 2nd MTP, a decompression insole was applied. If the pain was limited to the plantar aspect of the 2nd MTP, a decompression insole was worn. If swelling occurred, anti-inflammatory drugs were indicated to reduce inflammation. The combination of the two was appropriate for this condition. Toe exercises can improve balance and are worth trying. An in-depth understanding of the various etiologies of metatarsal and toe deformities is essential for successful treatment.

Using machine learning and big data to explore the drug resistance landscape in HIV

Drug resistance mutations (DRMs) appear in HIV under treatment pressure. DRMs are commonly transmitted to naive patients. The standard approach to reveal new DRMs is to test for significant frequency differences of mutations between treated and naive patients. However, we then consider each mutation individually and cannot hope to study interactions between several mutations. Here, we aim to leverage the ever-growing quantity of high-quality sequence data and machine learning methods to study such interactions (i.e. epistasis), as well as try to find new DRMs.We trained classifiers to discriminate between Reverse Transcriptase Inhibitor (RTI)-experienced and RTI-naive samples on a large HIV-1 reverse transcriptase (RT) sequence dataset from the UK (n ≈ 55, 000), using all observed mutations as binary representation features. To assess the robustness of our findings, our classifiers were evaluated on independent data sets, both from the UK and Africa. Important representation features for each classifier were then extracted as potential DRMs. To find novel DRMs, we repeated this process by removing either features or samples associated to known DRMs.When keeping all known resistance signal, we detected sufficiently prevalent known DRMs, thus validating the approach. When removing features corresponding to known DRMs, our classifiers retained some prediction accuracy, and six new mutations significantly associated with resistance were identified. These six mutations have a low genetic barrier, are correlated to known DRMs, and are spatially close to either the RT active site or the regulatory binding pocket. When removing both known DRM features and sequences containing at least one known DRM, our classifiers lose all prediction accuracy. These results likely indicate that all mutations directly conferring resistance have been found, and that our newly discovered DRMs are accessory or compensatory mutations. Moreover, we did not find any significant signal of epistasis, beyond the standard resistance scheme associating major DRMs to auxiliary mutations.Author summaryAlmost all drugs to treat HIV target the Reverse Transcriptase (RT) and Drug resistance mutations (DRMs) appear in HIV under treatment pressure. Resistant strains can be transmitted and limit treatment options at the population level. Classically, multiple statistical testing is used to find DRMs, by comparing virus sequences of treated and naive populations. However, with this method, each mutation is considered individually and we cannot hope to reveal any interaction (epistasis) between them. Here, we used machine learning to discover new DRMs and study potential epistasis effects. We applied this approach to a very large UK dataset comprising ≈ 55, 000 RT sequences. Results robustness was checked on different UK and African datasets.Six new mutations associated to resistance were found. All six have a low genetic barrier and show high correlations with known DRMs. Moreover, all these mutations are close to either the active site or the regulatory binding pocket of RT. Thus, they are good candidates for further wet experiments to establish their role in drug resistance. Importantly, our results indicate that epistasis seems to be limited to the classical scheme where primary DRMs confer resistance and associated mutations modulate the strength of the resistance and/or compensate for the fitness cost induced by DRMs.

Prevention of middle ear barotrauma with oxymetazoline/fluticasone treatment

Prevention of middle ear barotrauma with oxymetazoline/fluticasone treatment Middle ear barotrauma (MEB) is a common complication of hyperbaric oxygen (HBO2) therapy. It has been reported in more than 40% of HBO2 treatments and can interrupt the sequence of HBO2. MEB may lead to pain, tympanic membrane rupture, and even hearing loss.The aim of this study was to determine if pretreatment with intranasal fluticasone and oxymetazoline affected the incidence of MEB. We conducted a retrospective chart review of subjects undergoing HBO2 at our institution between February 1, 2014, and May 31, 2019. Subjects in the fluticasone/oxymetazoline (FOT) treatment group used intranasal fluticasone 50 mcg two times per day and oxymetazoline 0.05% one spray two times per day beginning 48 hours prior to initial HBO2. Oxymetazoline was discontinued after four days. Fluticasone was continued for the duration of HBO2 therapy. A total of 154 unique subjects underwent 5,683 HBO2 treatments: 39 unique subjects in the FOT group underwent 1,501 HBO2; 115 unique subjects in the nFOT (no oxymetazoline or fluticasone treatment) group underwent 4,182 HBO2 treatments. The incidence of MEB was 15.4% in the FOT group and 16.2% in the nFOT group. This was not a statistically significant difference (OR = 0.77; p = 0.636). Treatment pressure, age over 65 years, male sex, and BMI were not associated with a difference in MEB incidence. In summary, pretreatment with intranasal oxymetazoline and fluticasone in patients undergoing HBO2 did not significantly reduce MEB. More investigation with larger numbers of participants and prospective studies could further clarify this issue.

Selective treatment pressure in colon cancer drives the molecular profile of resistant circulating tumor cell clones

The characterization of circulating tumor cells (CTCs) holds promises for precision medicine because these cells are an important clinical indicator of treatment efficacy. We established the first and still only nine permanent colon CTC lines from peripheral blood samples of a patient with metastatic colon cancer collected at different time points during treatment and cancer progression. The study objectives were (i) to compare the gene expression profiles of these CTC lines, and (ii) to determine the main features acquired during treatment. The number of upregulated genes was higher in the CTC lines obtained after treatment, indicating that they acquired properties to escape treatment pressure. Among these upregulated genes, some are involved in the mTOR and PI3K/AKT signaling pathways. Moreover, cytidine deaminase expression was significantly increased in the CTC lines obtained after failure of the first- and second-line 5-fluorouracile-based treatments, suggesting that these CTCs can eliminate this specific drug and resist to therapy. Several enzymes involved in xenobiotic metabolism also were upregulated after treatment, suggesting the activation of detoxification mechanisms in response to chemotherapy. Finally, the significant higher expression of aldolase B in four of the six CTC lines obtained after treatment withdrawal and cancer progression indicated that these clones originated from liver metastases. In conclusion, these CTC lines generated at different time points during treatment of metastatic colon cancer in a single patient are characterized by the deregulation of different genes that promote (i) drug resistance, (ii) xenobiotic and energy metabolism, and (iii) stem cell properties and plasticity.

The Influence of Supercritical Carbon Dioxide on Graham Flour Enzyme Polyphenol Oxidase Activity

Graham flour is a form of whole wheat flour made by grinding the endosperm and is thus also the most nutritious. Generally, the enzyme polyphenol oxidase (PPO) catalyzes two different reactions in the presence of molecular oxygen: the hydroxylation of monophenols to ortho-diphenol and the oxidation of o-diphenol to o-quinone. The purpose of the work was to inactivate PPO activity to extend the shelf life of graham flour and at the same time preserve all the of its high-quality properties. The influence of supercritical CO2 (scCO2) treatment on PPO activity in graham flour was investigated. First, graham flour was exposed to scCO2 conditions, then the proteins were extracted, and in the last step the concentration of total proteins and the specific activity of the PPO enzyme were determined by spectrophotometric assay. PPO activity decreased with an increase in treatment pressure. Furthermore, the flour quality characteristics that meet all needs for wheat end-use products after scCO2 treatment have been preserved. No major changes in the structure of the granulate or shape of the flour particles were observed. A slightly reduced value of the moisture content in scCO2-treated graham flour also implies an extension of the shelf life.

Effects of CNS Demyelination and Myelin Recovery on Urinary Physiology

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Of note, over 80% of MS patients have urinary symptoms as one of their earliest symptoms. Since MS patients often live into older age, urinary incontinence and retention are significant problems for which few if any effective preventive or therapeutic options are available. The mechanisms by which MS contributes to urinary dysfunction are not well understood. We propose to elucidate the impact of demyelination on urinary performance using the cuprizone model, a model used to study the effects of CNS demyelination and spontaneous remyelination. We hypothesize that CNS demyelination in the cuprizone model will result in aberrant changes in urinary function, and that after remyelination occurs this dysfunction will be alleviated. C57Bl/6 mice were treated with cuprizone (0.2% w/w) for four weeks to induce demyelination. One group was allowed four additional weeks to recover from demyelination, while the other continued cuprizone treatment. Following this eight-week treatment, pressure/flow cystometry, electromyography, and molecular studies were performed to assess demyelination-induced differences in urinary performance. Cuprizone-recovery mice displayed improvements in cystometric function compared to their demyelinated littermates, as seen through improved volume sensitivity and voiding efficiency. Pharmacologic studies showed no significant changes in contractile responsiveness. Thus, we conclude that CNS demyelination results in aging-like phenotype and urinary dysfunction consistent with that observed in clinical disease. Therapeutics aimed at increasing the remyelination potential of the CNS neurons offer the possibility of alleviating urinary dysfunction associated with MS.

The evaluation of in-chamber sound levels during hyperbaric oxygen applications: Results of 41 centres

Introduction: Noise has physical and psychological effects on humans. Recommended exposure limits are exceeded in many hospital settings; however, information about sound levels in hyperbaric oxygen treatment chambers is lacking. This study measured in-chamber sound levels during treatments in Turkish hyperbaric centres. Methods: Sound levels were measured using a sound level meter (decibel meter). All chambers were multiplace with similar dimensions and shapes. Eight measurements were performed in each of 41 chambers; three during compression, three during decompression, and two at treatment pressure, one during chamber ventilation (flushing) and one without ventilation. At each measurement a sound sample was collected for 25 seconds and A-weighted equivalent (LAeq) and C-weighted peak (LCpeak) levels were obtained. Recorded values were evaluated in relation to sound level limits in regulations. Results: The highest sound level measured in the study was 100.4 dB(A) at treatment pressure while ventilation was underway and the lowest was 40.5 dB(A) at treatment pressure without ventilation. Most centres had sound levels between 70 dB and 85 dB throughout the treatment. Ventilation caused significant augmentation of noise. Conclusions: The chambers were generally safe in terms of noise exposure. Nevertheless, hyperbaric chambers can be very noisy environments so could pose a risk for noise-related health problems. Therefore, they should be equipped with appropriate noise control systems. Silencers are effective in reducing noise in chambers. Thus far, hyperbaric noise research has focused on chambers used for commercial diving. To our knowledge, this is the first study to investigate noise in hospital-based chambers during medical treatments.

Optimizing various parameters influencing mechanical properties of banana/coir natural fiber composites using grey relational analysis and artificial neural network models

The natural fibers of banana and coir from southern part of India was taken as the reinforcement material. Taguchi-based grey relational analysis was used for optimizing the factors influencing tensile, flexural and impact strength of banana/coir composites. Banana wt%, coir wt%, alkali treatment %, pressure and temperature during compression moulding process were the five major factors used for optimizing the mechanical strengths of epoxy-based composites. Grey relational analysis observed 20% banana/15% coir/3% alkali treatment/16 MPa pressure and 100°C temperature combination having the maximum mechanical properties in 16 trial combinations. The signal-to-noise ratio table of grey relational analysis showed combination with 20% banana /15% coir/5% alkali treatment/16 MPa pressure and 100°C temperature having optimized mechanical properties. Banana has the highest rank in improving the mechanical strength of natural composites, followed by coir, alkali treatment %, pressure and temperature. The graph between actual and artificial neural network computed results observed high correlation, proving that network topology of 5-3-1 with five factors, three hidden nodes and one response is the best method for analyzing the parameters in mechanical strength. Hybrid fiber composites with NaOH treatment showed hackles in interface with improved interfacial bonding during SEM analysis.