The present study was conducted to evaluate the clinical outcomes of a modified all-inside arthroscopic repair technique via anterolateral and accessory anterolateral port for anterior talofibular ligament (ATFL) repair. A consecutive series of 32 patients (34 ankles) with chronic ankle instability were included and treated with the modified all-inside arthroscopic repair. The function was assessed using the American Orthopaedic Foot and Ankle Society (AOFAS), visual analog score (VAS) score system, the Sefton grading system, and the anterior drawer test and talar tilt test. A total of 29 cases (30 ankles) were followed up for a mean of 33.7 ± 4.5 (range 30-44) months. Based on the Sefton grading system, 12 patients were regarded as excellent, 13 were good, 2 were fair, and 2 were poor. Twenty-five cases (86.2%) achieved satisfactory functional results. Ankle mobility returned to normal in 93% of patients. The AOFAS scores increased from 55.1 ± 12.3 (range 25-69) preoperatively to 89.7 ± 5.9 (range 74-100) (P < .001) at the last follow-up, while the VAS score decreased significantly (P < .001). There was no wound infection or nerve injury in all cases. In conclusion, based on high satisfaction rate in terms of ankle mobility and low complication rate, the modified all-inside arthroscopic repair of ATFL via anterolateral and accessory anterolateral port appears to be an effective treatment method for chronic ankle instability. Further studies are needed.

It is reported that both adductor canal block (ACB) and femoral nerve block (FNB) are commonly used methods for postoperative analgesia in anterior cruciate ligament (ACL) reconstruction. Currently, no record has compared the efficacy of postoperative pain relief and the influence to quadriceps strength between them. This study aims to provide a protocol to compare the efficacy and safety between ACB and FNB for the postoperative analgesia of ACL reconstruction.

Erythrina corallodendron L., a kind of landscape tree, has long been used as a traditional medicine. In this study, the composition of essential oil extracted from the leaves was analysed by GC-MS (gas chromatograph-mass spectrometer), with linalool identified as the main compound. Its cytotoxicity against MDA-MB-231, MCF-7 and HMLE cells was examined by MTT and cloning assays. Transwell and wound-healing assays were used to examine the inhibition of migration and invasion. Western blot, qRT-PCR and immunofluorescence staining were used to measure the mRNA and protein expression of factors related to EMT (snail, slug, E-cadherin, N-cadherin and vimentin). The essential oil of Erythrina corallodendron leaves was found to inhibit the proliferation, migration and invasion of breast cancer cells in a dose-dependent manner. The findings of this study suggest that the essential oil of E. corallodendron leaves may merit further investigation as a potential clinical or adjuvant drug for treating breast cancer migration and invasion.

Knee osteoarthritis (KOA), a common clinical chronic osteoarthropathy, has adverse effects on the working ability and life quality of patients. At present, acupotomy and nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely applied on KOA in China and has achieved satisfactory results. However, there is no systematic review comparing the effectiveness of these two therapies for KOA. Therefore, this study will assess the efficacy and safety of acupotomy in treating KOA.

Periventricular nodular heterotopia (PNH) is the most common type of epileptogenic neuronal migration disorder, and often presents with epilepsy and reading disability. The functional role of ectopic nodules has been widely studied. However, the associated structural cortical and subcortical volumetric alterations have not been well characterized. Moreover, it is unknown whether a correlation between volumetric changes and behavioral problems exists.40 subjects with bilateral PNH and 40 matched healthy controls were enrolled in this study. The total cerebral, gray matter, white matter, and cerebrospinal fluid (CSF) volumes were compared between the two groups. Furthermore, structural and functional correlations were evaluated between volumetric changes and reading disability.There were no significant differences detected in total cerebral, gray matter or CSF volumes between the two groups, but there was a significant trend of larger gray-matter volume in PNH. Specifically, smaller white matter volumes were found in the PNH patients. Moreover, the volume of white matter was negatively related to time in the digit rapid naming task and a similar but insignificant trend was seen between the volume of gray matter and backward digit span.These findings suggest that reading disability exists in our sample of bilateral PNH. Periventricular nodules would have normally migrated to the overlying cortex. However, the total cerebral, gray matter, and CSF volumes were unaffected. Alterations in neuronal migration may have an impact in the white matter associated reading dysfluency, that is, visually normal.

Sensitive laser desorption/ionization obtained via a sublimation-coated 1,5-diaminonaphthalene (1,5-DAN) matrix allowed dual polarity MALDI-IMS analysis on the same pixel points across the jejunal mucosal region in rat small intestine which yielded high-spatial-resolution (10 μm) ion images of several lipid species correlated with the same histological features.

Proton pump inhibitors (PPIs) are an effective treatment for eosinophilic esophagitis (EoE); however, only 30% to 60% of patients respond. Common genetic variants in CYP2C19 and STAT6 associate with PPI plasma concentration and magnitude of inflammatory response, respectively. Our objective was to determine if genetic variation in the genes for CYP2C19 and STAT6 influence differentiation between PPI responsive esophageal eosinophilia versus PPI nonresponsive EoE (PPI-REE, PPI-nonresponsive EoE).

A subpopulation of the arctic fox lineage of rabies virus has circulated extensively in red fox populations of Ontario, Canada, between the 1960s and 1990s. An intensive wildlife rabies control program, in which field operations were initiated in 1989, resulted in elimination of the disease in eastern Ontario. However in southwestern Ontario, as numbers of rabid foxes declined the proportion of skunks confirmed to be infected with this rabies virus variant increased and concerted control efforts targeting this species were employed to eliminate the disease. Since 2012 no cases due to this viral variant were reported in southwestern Ontario until 2015 when a single case of rabies due to the arctic fox variant was reported in a bovine. Several additional cases have been documented subsequently. Since routine antigenic typing cannot discriminate between the variants which previously circulated in Ontario and those from northern Canada it was unknown whether these recent cases were the result of a new introduction of this variant or a continuation of the previous enzootic. To explore the origins of this new outbreak whole genome sequences of a collection of 128 rabies viruses recovered from Ontario between the 1990s to the present were compared with those representative of variants circulating in the Canadian north. Phylogenetic analysis shows that the variant responsible for current cases in southwestern Ontario has evolved from those variants known to circulate in Ontario previously and is not due to a new introduction from northern regions. Thus despite ongoing passive surveillance the persistence of wildlife rabies went undetected in the study area for almost three years. The apparent adaptation of this rabies virus variant to the skunk host provided the opportunity to explore coding changes in the viral genome which might be associated with this host shift. Several such changes were identified including a subset for which the operation of positive selection was supported. The location of a small number of these amino acid substitutions in or close to protein motifs of functional importance suggests that some of them may have played a role in this host shift.

Sexual development is a key evolutionary innovation of eukaryotes. In many species, mating involves interaction between compatible mating partners that can undergo cell and nuclear fusion and subsequent steps of development including meiosis. Mating compatibility in fungi is governed by the mating type (MAT) loci. In basidiomycetes, the ancestral state is hypothesized to be tetrapolar, with two genetically unlinked MAT loci containing homeodomain transcription factor genes (HD locus) and pheromone and pheromone receptor genes (P/R locus), respectively. Alleles at both loci must differ between mating partners for completion of sexual development. However, there are also basidiomycetes with bipolar mating systems, which can arise through genomic linkage of the HD and P/R loci. In the order Tremellales, bipolarity is found only in the pathogenic Cryptococcus species. Here, we describe the analysis of MAT loci from 24 species of the Trichosporonales, a sister order to the Tremellales. In all of the species analyzed, the MAT loci are fused and a single HD gene is present in each mating type, similar to the organization in the pathogenic Cryptococci. However, the HD and P/R allele combinations in the Trichosporonales are different from those in the pathogenic Cryptococci. This and the existence of tetrapolar species in the Tremellales suggest that fusion of the HD and P/R loci occurred independently in the Trichosporonales and pathogenic Cryptococci, supporting the hypothesis of convergent evolution towards fused MAT regions, similar to previous findings in other fungal groups. Unlike the fused MAT loci in several other basidiomycete lineages though, the gene content and gene order within the fused MAT loci are highly conserved in the Trichosporonales, and there is no apparent suppression of recombination extending from the MAT loci to adjacent chromosomal regions, suggesting different mechanisms for the evolution of physically linked MAT loci in these groups.

Heart disease is the leading cause of death in the western world. Attaining a mechanistic understanding of human heart development and homeostasis and the molecular basis of associated disease states relies on the use of animal models. Here, we present the cardiac proteomes of 4 model vertebrates with dual circulatory systems: the pig (Sus scrofa), the mouse (Mus musculus), and 2 frogs (Xenopus laevis and Xenopus tropicalis). Determination of which proteins and protein pathways are conserved and which have diverged within these species will aid in our ability to choose the appropriate models for determining protein function and to model human disease. We uncover mammalian- and amphibian-specific, as well as species-specific, enriched proteins and protein pathways. Among these, we find and validate an enrichment in cell-cycle-associated proteins within Xenopus laevis. To further investigate functional units within cardiac proteomes, we develop a computational approach to profile the abundance of protein complexes across species. Finally, we demonstrate the utility of these data sets for predicting appropriate model systems for studying given cardiac conditions by testing the role of Kielin/chordin-like protein (Kcp), a protein found as enriched in frog hearts compared to mammals. We establish that germ-line mutations in Kcp in Xenopus lead to valve defects and, ultimately, cardiac failure and death. Thus, integrating these findings with data on proteins responsible for cardiac disease should lead to the development of refined, species-specific models for protein function and disease states.

Integrated disease management, disability and inclusion (DMDI) for NTDs is increasingly prioritised. There is limited evidence on the effectiveness of integrated DMDI from the perspective of affected individuals and how this varies by differing axes of inequality such as age, gender, and disability. We used narrative methods to consider how individuals' unique positions of power and privilege shaped their illness experience, to elucidate what practical and feasible steps could support integrated DMDI in Liberia and beyond.

The current study highlights, for the first time, cloning, overexpression and purification of the novel interferon epsilon (IFNƐ), from the Arabian camel Camelus dromedaries. The study then assesses the cytotoxicity of IFNε against two human breast cancer cell lines MDA-MB-231 and MCF-7. Full-length cDNA encoding interferon epsilon (IFNε) was isolated and cloned from the liver of the Arabian camel, C. dromedarius using reverse transcription-polymerase chain reaction. The sequence analysis of the camel IFNε cDNA showed a 582-bp open reading frame encoding a protein of 193 amino acids with an estimated molecular weight of 21.230 kDa. A BLAST search analysis revealed that the C. dromedarius IFNε shared high sequence identity with the IFN genes of other species, such as Camelus ferus, Vicugna pacos, and Homo sapiens. Expression of the camel IFNε cDNA in Escherichia coli gave a fusion protein band of 24.97 kDa after induction with either isopropyl β-D-1-thiogalactopyranoside or lactose for 5 h. Recombinant IFNε protein was overexpressed in the form of inclusion bodies that were easily solubilized and refolded using SDS and KCl. The solubilized inclusion bodies were purified to apparent homogeneity using nickel affinity chromatography. We examined the effect of IFNε on two breast cancer cell lines MDA-MB-231 and MCF-7. In both cell lines, IFNε inhibited cell survival in a dose dependent manner as observed by MTT assay, morphological changes and apoptosis assay. Caspase-3 expression level was found to be increased in MDA-MB-231 treated cells as compared to untreated cells.

Despite the importance of microbial activity in mobilizing arsenic in groundwater aquifers, the phylogenetic distribution of contributing microbial metabolisms is understudied. Groundwater samples from Ohio aquifers were analyzed using metagenomic sequencing to identify functional potential that could drive arsenic cycling, and revealed mechanisms for direct (i.e., Ars system) and indirect (i.e., iron reduction) arsenic mobilization in all samples, despite differing geochemical conditions. Analyses of 194 metagenome-assembled genomes (MAGs) revealed widespread functionality related to arsenic mobilization throughout the bacterial tree of life. While arsB and arsC genes (components of an arsenic resistance system) were found in diverse lineages with no apparent phylogenetic bias, putative aioA genes (aerobic arsenite oxidase) were predominantly identified in Methylocystaceae MAGs. Both previously described and undescribed respiratory arsenate reduction potential via arrA was detected in Betaproteobacteria, Deltaproteobacteria, and Nitrospirae MAGs, whereas sulfate reduction potential was primarily limited to members of the Deltaproteobacteria and Nitrospirae. Lastly, iron reduction potential was detected in the Ignavibacteria, Deltaproteobacteria, and Nitrospirae. These results expand the phylogenetic distribution of taxa that may play roles in arsenic mobilization in subsurface systems. Specifically, the Nitrospirae are a much more functionally diverse group than previously assumed and may play key biogeochemical roles in arsenic-contaminated ecosystems.

Amyotrophic lateral sclerosis (ALS) is a rare, progressive neurodegenerative disease. There is heterogeneity of clinical phenotypes while a clinical characterization of ALS in Cyprus is still lacking. The aim of this 30-year retrospective study of ALS in Cyprus is to determine the demographic characteristics of patients, the clinical features of the disease, the uptake of supportive therapies and factors influencing survival.

The five-year survival rate of patients diagnosed with advanced pancreatic ductal adenocarcinoma (PDAC) has remained static at <5% despite decades of research. With the exception of erlotinib, clinical trials have failed to demonstrate the benefit of any targeted therapy for PDAC despite promising results in preclinical animal studies. The development of more refined mouse models of PDAC which recapitulate the carcinogenic progression from non-neoplastic, adult exocrine subsets of pancreatic cells to invasive carcinoma in humans are needed to facilitate the accurate translation of therapies to the clinic. To study acinar cell-derived PDAC initiation, we developed a genetically engineered mouse model of PDAC, called KPT, utilizing a tamoxifen-inducible Cre recombinase/estrogen receptor (ESR1) fusion protein knocked into the Ptf1a locus to activate the expression of oncogenic KrasG12D and Trp53R270H alleles in mature pancreatic acinar cells. Oncogene-expressing acinar cells underwent acinar-to-ductal metaplasia, and formed pancreatic intraepithelial neoplasia lesions following the induction of oncogene expression. After a defined latency period, oncogene-expressing acinar cells initiated the formation of highly differentiated and fibrotic tumors, which metastasized to the lungs and liver. Whole-transcriptome analysis of microdissected regions of acinar-to-ductal metaplasia and histological validation experiments demonstrated that regions of acinar-to-ductal metaplasia are characterized by the deposition of the extracellular matrix component hyaluronan. These results indicate that acinar cells expressing KrasG12D and Trp53R270H can initiate PDAC development in young adult mice and implicate hyaluronan deposition in the formation of the earliest characterized PDAC precursor lesions (and the progression of pancreatic cancer). Further studies are necessary to provide a comprehensive characterization of PDAC progression and treatment response in KPT mice and to investigate whether the KPT model could be used as a tool to study translational aspects of acinar cell-derived PDAC tumorigenesis.

Malnutrition in pregnancy remains unacceptably high across all regions of Africa though promising progresses have been made globally. Primary studies might not be sufficient to portrait a comprehensive picture of malnutrition during pregnancy and its main risk factors. Therefore, we intended to review the burden of malnutrition, for this specific review implies to protein energy malnutrition, during pregnancy in Africa to present its magnitude and determinant factors.

Zimbabwe faces an uncertain future for condom funding and potential condom insecurity as international donors prioritize creating more self-sustaining markets and the government identifies how to best ensure access and uptake. We tested the impact of an intensive intervention on demand and supply after a price increase to the social marketed condom, Protector Plus. The study occurred during a deteriorating economy and pressure to reach sustainability quickly. We highlight where strategic donor investments can impact condom programming and markets.

Deposition of polydisperse particles representing nasal spray application in a human nasal cavity was performed under transient breathing profiles of sniffing, constant flow, and breath hold. The LES turbulence model was used to describe the fluid phase. Particles were introduced into the flow field with initial spray conditions, including spray cone angle, insertion angle, and initial velocity. Since nasal spray atomizer design determines the particle conditions, fifteen particle size distributions were used, each defined by a log-normal distribution with a different volume mean diameter (Dv50). Particle deposition in the anterior region was approximately 80% when Dv50 > 50μm, and this decreased to 45% as Dv50 decreased to 10μ m for constant and sniff breathing conditions. The decrease in anterior deposition was countered with increased deposition in the middle and posterior regions. The significance of increased deposition in the middle region for drug delivery shows there is potential for nasal delivered drugs to reach the highly vascularised mucosal walls in the main nasal passages. For multiple targeted deposition sites, an optimisation equation was introduced where deposition results of any two targeted sites could be combined and a weighting between 0 to 1 was applied to each targeted site, representing the relative importance of each deposition site.

Exaggerated vasoconstriction plays important roles in vascular complication in aging and many diseases like diabetes. Here, we investigated the protective effect of Psiadia punctulata (PP) on advanced glycation end products (AGEs)-induced aggravated vasoconstriction. The effect of total methanol extract of PP leaves (PPT) on AGE-induced vascular injury was studied through bioassay-guided fractionation procedures in order to find the bioactive fraction and isolate the bioactive compounds. Vascular reactivity was studied using the isolated artery technique by adding cumulative concentrations of phenylephrine (PE) or acetyl choline (ACh). In addition, the antiglycating effect, as well as the effect on AGEs intermediates dityrosine and N`-formylkynurenine and their radical scavenging activity were measured. The results showed that PPT alleviated the AGEs-induced aggravated vasoconstriction in a concentration-dependent manner. The bioassay guided fractionation procedures suggested the chloroform fraction (Fr I) to be responsible for the activity. Chemical investigation of this fraction resulted in isolation of four major bioactive compounds that were identified as: umuhengerin (1), gardenin (2), luteolin-3`,4`-dimethyl ether (3), and 5,3`-dihydroxy-6,7,4`,5`-tetramethoxyflavone (4). The four compounds alleviated the exaggerated vasoconstriction in a dose dependent manner. In search for their mechanism of action, we observed that PPT, Fr. I and the isolated compounds did not improve the impaired vasodilation associated with AGEs exposure. PPT, Fr. I and the isolated compounds 1-4 inhibited AGEs formation and their protein oxidation intermediates. Furthermore, PPT, Fr. I and the isolated compounds 1-4 showed weak radical scavenging activity with compound 4 as the most potent. In conclusion, PPT appears to protect against AGEs-induced exaggerated vasoconstriction through antiglycation and radical scavenging activities.

A novel GH9 cellulase (AMOR_GH9A) was discovered by sequence-based mining of a unique metagenomic dataset collected at the Jan Mayen hydrothermal vent field. AMOR_GH9A comprises a signal peptide, a catalytic domain and a CBM3 cellulose-binding module. AMOR_GH9A is an exceptionally stable enzyme with a temperature optimum around 100°C and an apparent melting temperature of 105°C. The novel cellulase retains 64% of its activity after 4 hours of incubation at 95°C. The closest characterized homolog of AMOR_GH9A is TfCel9A, a processive endocellulase from the model thermophilic bacterium Thermobifida fusca (64.2% sequence identity). Direct comparison of AMOR_GH9A and TfCel9A revealed that AMOR_GH9A possesses higher activity on soluble and amorphous substrates (phosphoric acid swollen cellulose, konjac glucomannan) and has an ability to hydrolyse xylan that is lacking in TfCel9A.