Sequential bilateral total ankle replacements: No difference in patient-reported outcomes between the first and second ankle.

BACKGROUND: Total ankle replacement is an established treatment for end-stage arthritis. However, there is little data examining outcomes in sequential bilateral replacements. This study aimed to compare outcomes between first and second ankles in sequential replacement. METHODS: Patients were retrospectively contacted to complete a follow-up questionnaire including the Manchester-Oxford Foot Questionnaire (MOXFQ), EQ-5D-3 L, and a question assessing satisfaction. Electronic records identified demographics, procedural details, and complications. RESULTS: Twenty patients underwent sequential bilateral ankle replacement over the study period. At a mean follow-up of four years, 18 patients completed the follow-up questionnaire. There was no statistically significant difference between first and second ankles in terms of MOXFQ score, EQ-5D-3 L or satisfaction. Eleven complications were noted. CONCLUSIONS: We report excellent outcomes after sequential bilateral ankle replacement with no difference in outcomes between first and second ankles. These results can be used to counsel patients in the future and manage expectations. LEVEL OF EVIDENCE: IV.

The interaction between LC8 and LCA5 reveals a novel oligomerization function of LC8 in the ciliary-centrosome system.

Dynein light chain LC8 is a small dimeric hub protein that recognizes its partners through short linear motifs and is commonly assumed to drive their dimerization. It has more than 100 known binding partners involved in a wide range of cellular processes. Recent large-scale interaction studies suggested that LC8 could also play a role in the ciliary/centrosome system. However, the cellular function of LC8 in this system remains elusive. In this work, we characterized the interaction of LC8 with the centrosomal protein lebercilin (LCA5), which is associated with a specific form of ciliopathy. We showed that LCA5 binds LC8 through two linear motifs. In contrast to the commonly accepted model, LCA5 forms dimers through extensive coiled coil formation in a LC8-independent manner. However, LC8 enhances the oligomerization ability of LCA5 that requires a finely balanced interplay of coiled coil segments and both binding motifs. Based on our results, we propose that LC8 acts as an oligomerization engine that is responsible for the higher order oligomer formation of LCA5. As LCA5 shares several common features with other centrosomal proteins, the presented LC8 driven oligomerization could be widespread among centrosomal proteins, highlighting an important novel cellular function of LC8.

The DUG Pathway Governs Degradation of Intracellular Glutathione in Aspergillus nidulans.

Glutathione (GSH) is an abundant tripeptide that plays a crucial role in shielding cellular macromolecules from various reactive oxygen and nitrogen species in fungi. Understanding GSH metabolism is of vital importance for deciphering redox regulation in these microorganisms. In the present study, to better understand the GSH metabolism in filamentous fungi, we investigated functions of the dugB and dugC genes in the model fungus Aspergillus nidulans These genes are orthologues of dug2 and dug3, which are involved in cytosolic GSH degradation in Saccharomyces cerevisiae The deletion of dugB, dugC, or both resulted in a moderate increase in the GSH content in mycelia grown on glucose, reduced conidium production, and disturbed sexual development. In agreement with these observations, transcriptome data showed that genes encoding mitogen-activated protein (MAP) kinase pathway elements (e.g., steC, sskB, hogA, and mkkA) or regulatory proteins of conidiogenesis and sexual differentiation (e.g., flbA, flbC, flbE, nosA, rosA, nsdC, and nsdD) were downregulated in the ΔdugB ΔdugC mutant. Deletion of dugB and/or dugC slowed the depletion of GSH pools during carbon starvation. It also reduced accumulation of reactive oxygen species and decreased autolytic cell wall degradation and enzyme secretion but increased sterigmatocystin formation. Transcriptome data demonstrated that enzyme secretions-in contrast to mycotoxin production-were controlled at the posttranscriptional level. We suggest that GSH connects starvation and redox regulation to each other: cells utilize GSH as a stored carbon source during starvation. The reduction of GSH content alters the redox state, activating regulatory pathways responsible for carbon starvation stress responses.IMPORTANCE Glutathione (GSH) is a widely distributed tripeptide in both eukaryotes and prokaryotes. Owing to its very low redox potential, antioxidative character, and high intracellular concentration, GSH profoundly shapes the redox status of cells. Our observations suggest that GSH metabolism and/or the redox status of cells plays a determinative role in several important aspects of fungal life, including oxidative stress defense, protein secretion, and secondary metabolite production (including mycotoxin formation), as well as sexual and asexual differentiations. We demonstrated that even a slightly elevated GSH level can substantially disturb the homeostasis of fungi. This information could be important for development of new GSH-producing strains or for any biotechnologically relevant processes where the GSH content, antioxidant capacity, or oxidative stress tolerance of a fungal strain is manipulated.

A versatile technique for in situ investigation of the effect of thin film cracking on gas permeation of coated flexible polymers.

In this work, we report the development of a measurement chamber linked with a quadrupole mass spectrometer (QMS) for in situ investigation of the effect of thin film cracking on the gas permeation of coated flexible polymeric substrates. The chamber enables the establishment of a bulged state of the substrate/coating system, which causes the cracking of the coating layer. The increase in the gas permeation rate due to the presence of cracks can be monitored precisely using the QMS without movement or re-clamping of the samples between each measurement step. This method eliminates the probability of uncontrollable mechanical changes in the sample, and with the mass spectrometer, high sensitivity, reliability, and reproducibility of the experimental data become available.

Six cases of Solobacterium moorei isolated alone or in mixed culture in Hungary and comparison with previously published cases.

Solobacterium moorei is a strict anaerobic gram-positive rod. It is found in the human microbiota in different parts of the body, but it also appears to be an opportunistic pathogen in some infectious processes. We describe six cases of severe infections identified in 2016 in which S. moorei was isolated alone or in mixed culture involving other anaerobes or both aerobic and anaerobic bacteria. Three cases were associated with the oral cavity, including a middle ear infection, a wound infection after total laryngectomy, and a mandibular abscess as a result of bisphosphonate therapy. In the other three patients, the sites of infection had no connections with the oral cavity and included chronic osteomyelitis of the tibia, a superinfection of cutaneous tuberculosis associated with hidradenitis suppurativa, and the isolation of S. moorei from the blood culture of a cachectic man with several comorbidities. Based on our findings, S. moorei does not appear to be that virulent of a bacterium; except for the case with bacteraemia, S. moorei was recovered as a co-pathogen in patients with several immunosuppressive predisposing factors. We highlight the finding that the routine use of MALDI-TOF MS in microbiology laboratories can in a timely and detailed manner identify members of mixed infections involving different anaerobic bacteria that may be rare and difficult-to-culture and identify species, such as S. moorei.

Phenotypic Characterization of the c.1679+1643G>T (1811+1643G>T) Mutation in Hispanic Cystic Fibrosis Patients.

Cystic fibrosis (CF) is the most common fatal genetic diseases in the United States in Caucasians. More than 2000 genetic mutations have been described and CF is now known to affect other races. The incidence of CF in individuals of Hispanic descent is estimated to be 1:9200. An uncommon mutation, 1811+1643G>T, was recently reported. We report four patients with the 1811+1643G>T mutation (homozygous or heterozygous) and describe their clinical features and compare them to the remainder of our Hispanic cohort group. The homozygous patients had a more severe phenotype compared to the Hispanic cohort in the following areas: their pancreatic status, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), chronic Pseudomonas aeruginosa (PA) colonization, pulmonary exacerbations requiring oral and intravenous antibiotics, and hospitalization rate. These preliminary findings suggest that future studies investigating the clinical trajectory with a larger cohort of patients homozygous for the 1811+1643G>T mutation are needed.

[Plant-based diets: a review]. / A növényi alapú étrendrol.

Plant-based diet is an old-new trend in nutrition. In this review based on a historical context, we wish to introduce this popular nutritional trend. Our aim is to present plant-based diet as a primary measure for prevention. We intend to critically analyse some past stereotypes related to plant-based diet - whose main components include fruits, vegetables, whole grains, legumes, nuts and seeds - according to the literature (e.g. protein, vitamin B12, folic acid, and iron intake) by doing so we wish to create an adequate conceptual basis for its interpretation. We discuss positive physiological effects of plant-based diet and its possible role in diseases risk reduction. Cardiovascular and metabolic diseases developing due to obesity could be prevented by a properly compiled plant-based diet. For patients with cancer minimizing the intake of foods of animal origin - as opposed to plant-based ones - has proved to have positive effects. Our review suggests this diet can be used in a number of diseases and it also provides long-term sustainable solutions for the health care challenges of the newest era. Orv. Hetil., 2016, 157(47), 1859-1865.

[Current practice of positive family planning service in the National Institute of Child Health in the last six years]. / A pozitív családtervezés gyakorlata az Országos Gyermekegészségügyi Intézetben - az elmúlt hat év tükrében.

The aim of positive family planning is to prevent preterm delivery and congenital abnormalities. Using primer prevention models at this time helps to prevent the common disorders which are the leading causes of death. The mission of the National Institute of Child Health is to promote preconceptional health and thus, mother and baby's health. This article introduces the practice of our institute's family planning department and the last six years' experiences.

Necrolytic migratory erythema.

BACKGROUND: Necrolytic migratory erythema is considered to be a paraneoplastic dermatosis. The classical symptoms are associated with alpha-cell pancreatic islet cell tumor or 'glucagonoma'. Generally, extracutaneous hallmarks of this disease include weight loss, diabetes, anaemia and diarrhoea. OBSERVATION: We report a case of a 39-year-old woman with a 3-year history of recalcitrant psoriasiform eruption, who had no other associated symptoms on routine examination. Histologic examinations suggested necrolytic migratory erythema. Abdominal computer tomography was performed, which revealed a tumor in the tail of the pancreas. After distal resection of the pancreas her skin symptoms resolved in a few days time. Histology was consistent with glucagonoma. She is clinically well and symptomless and no signs of metastasis after 4 years. CONCLUSIONS: It is infrequent to have only necrolytic migratory erythema, hyperglucagonaemia and islet-cell tumor but no other extracutaneous symptoms in glucagonoma syndrome. To our knowledge, ours is the second such case reported in the literature. Skin symptoms are important, often they are the clue to the diagnosis of glucagonoma syndrome.

Short-term morphologic and functional effects of bromocriptine on pituitary prolactin cell adenomas in vitro.

Bromocriptine, a dopamine agonist, rapidly reduces profactin (PRL) blood levels in vivo; it also causes a marked reduction in tumor size in patients with lactotroph adenomas within 2 weeks of initiation of therapy. The effects are direct, as shown in vitro, and are thought to be due to inhibition of gene transcription that causes alteration in tumor cell morphology. However, the morphologic changes that account for a functional response within hours of administration have not been elucidated. We report the functional and morphologic changes in 7 pituitary lactotroph adenomas studied in vitro after 2, 24, and 48 hours of incubation with bromocriptine. In 2-hour incubations, PRL release rapidly fell to 46% to 74% of control; morphologic analysis revealed an increase in the cytoplasmic volume density (CVD) of secretory granules. After 24 hours of treatment, PRL release was maximally suppressed at 18% to 32 % of control; at 24 hours, the CVDs of secretory granules and lysosomes were increased, and they remained higher than in control cells at 48 hours. The CVD of rough endoplasmic reticulum was reduced at 2 hours in some tumors, but that of Golgi complexes was reduced only at 48 hours. Cell size was altered only to slightly below 80% of control and only after 48 hours of exposure in 2 or 3 tumors. This study indicates that inhibition of PRL secretion occurs within 2 hours of exposure to bromocriptine; the initial morphologic correlates are an increase in the CVD of secretory granules, suggesting inhibition of hormone release, and a decrease in rough endoplasmic reticulum, suggesting reduction of hormone synthesis. Lysosomal accumulation occurs within 24 hours, most likely reflecting degradation of the stored hormone. Subsequently, Golgi complexes involute as the next step in reduced hormone synthesis occurs, and cell shrinkage occurs relatively later. These findings correlate well with the rapid reduction in PRL blood levels and the slower tumor shrinkage documented clinically in patients with PRL cell adenomas.