Increased Activity Level Following Total Ankle Replacement Results in Improved Patient Reported Outcomes.

While evidence highlights increased activity levels following total ankle replacement (TAR), the correlation between postoperative activity changes and ankle-surgery-specific patient-reported outcomes is unexplored. This retrospective cohort study investigates the effect of activity level changes on patient-reported outcomes, including the Manchester-Oxford Foot Questionnaire (MOXFQ) and patient satisfaction following TAR. Patient records from a single center performing TARs between January 2014 and February 2023 were reviewed alongside patient questionnaires completed preoperatively and at a mean follow-up of 44 ± 31 months postoperatively (range 6-134 months). Activity participation pre and postoperatively was assessed and correlated with MOXFQ scores. Data from 89 patients was available for analysis (mean age 72.3 ± 8.9 years [range, 48-92]). Postoperatively, 31 patients (35%) increased, 42 (47%) maintained, and 16 (18%) decreased their activity levels. The mean time to return to regular activity was 23.4 weeks. Preoperative MOXFQ scores were similar across all groups (increased: 74.03 ± 14.00; maintained: 73.6 ± 13.9; decreased: 77.0 ± 15.5; p = .71). All groups showed significant improvements in MOXFQ scores from preoperative to postoperative assessments (p < .05). Patients with increased activity levels showed greater MOXFQ improvements (-61.6 ± 19.0) compared to those with decreased activity levels (-38.3 ± 26.6) (p < .01). Following TAR, 82% of patients maintained or increased their activity levels. Patients with increased postoperative activity exhibited superior improvements in MOXFQ scores. These findings underscore the importance of promoting physical activity for optimal outcomes following TAR.

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.

Competitive inhibition of the classical complement pathway using exogenous single-chain C1q recognition proteins.

Complement component C1q is a protein complex of the innate immune system with well-characterized binding partners that constitutes part of the classical complement pathway. In addition, C1q was recently described in the central nervous system as having a role in synapse elimination both in the healthy brain and in neurodegenerative diseases. However, the molecular mechanism of C1q-associated synapse phagocytosis is still unclear. Here, we designed monomer and multimer protein constructs, which comprised the globular interaction recognition parts of mouse C1q (globular part of C1q [gC1q]) as single-chain molecules (sc-gC1q proteins) lacking the collagen-like effector region. These molecules, which can competitively inhibit the function of C1q, were expressed in an Escherichia coli expression system, and their structure and capabilities to bind known complement pathway activators were validated by mass spectrometry, analytical size-exclusion chromatography, analytical ultracentrifugation, CD spectroscopy, and ELISA. We further characterized the interactions between these molecules and immunoglobulins and neuronal pentraxins using surface plasmon resonance spectroscopy. We demonstrated that sc-gC1qs potently inhibited the function of C1q. Furthermore, these sc-gC1qs competed with C1q in binding to the embryonal neuronal cell membrane. We conclude that the application of sc-gC1qs can reveal neuronal localization and functions of C1q in assays in vivo and might serve as a basis for engineering inhibitors for therapeutic purposes.

Neuronal-specific septin-3 binds Atg8/LC3B, accumulates and localizes to autophagosomes during induced autophagy.

In synapses that show signs of local apoptosis and mitochondrial stress and undergo neuro-immunological synapse pruning, an increase in the levels of the presynaptic protein, neuronal-specific septin-3 can be observed. Septin-3 is a member of the septin GTPase family with the ability to form multimers and contribute to the cytoskeleton. However, the function of septin-3 remains elusive. Here, we provide evidence that septin-3 is capable of binding the most-studied autophagy protein Atg8 homolog microtubule-associated protein 1 light chain 3B (LC3B), besides another homolog, GABA receptor-associated protein-like 2 (GABARAPL2). Moreover, we demonstrate that colocalization of septin-3 and LC3B increases upon chemical autophagy induction in primary neuronal cells. Septin-3 is accumulated in primary neurons upon autophagy enhancement or blockade, similar to autophagy proteins. Using electron microscopy, we also show that septin-3 localizes to LC3B positive membranes and can be found at mitochondria. However, colocalization results of septin-3 and the early mitophagy marker PTEN-induced kinase 1 (PINK1) do not support that binding of septin-3 to mitochondria is mitophagy related. We conclude that septin-3 correlates with synaptic/neuronal autophagy, binds Atg8 and localizes to autophagic membranes that can be enhanced with chemical autophagy induction. Based on our results, elevated septin-3 levels might indicate enhanced or impeded autophagy in neurons.

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.

De novo variants in neurodevelopmental disorders-experiences from a tertiary care center.

Up to 40% of neurodevelopmental disorders (NDDs) such as intellectual disability, developmental delay, autism spectrum disorder, and developmental motor abnormalities have a documented underlying monogenic defect, primarily due to de novo variants. Still, the overall burden of de novo variants as well as novel disease genes in NDDs await discovery. We performed parent-offspring trio exome sequencing in 231 individuals with NDDs. Phenotypes were compiled using human phenotype ontology terms. The overall diagnostic yield was 49.8% (n = 115/231) with de novo variants contributing to more than 80% (n = 93/115) of all solved cases. De novo variants affected 72 different-mostly constrained-genes. In addition, we identified putative pathogenic variants in 16 genes not linked to NDDs to date. Reanalysis performed in 80 initially unsolved cases revealed a definitive diagnosis in two additional cases. Our study consolidates the contribution and genetic heterogeneity of de novo variants in NDDs highlighting trio exome sequencing as effective diagnostic tool for NDDs. Besides, we illustrate the potential of a trio-approach for candidate gene discovery and the power of systematic reanalysis of unsolved cases.

Synaptic mitochondrial dysfunction and septin accumulation are linked to complement-mediated synapse loss in an Alzheimer's disease animal model.

Synaptic functional disturbances with concomitant synapse loss represent central pathological hallmarks of Alzheimer's disease. Excessive accumulation of cytotoxic amyloid oligomers is widely recognized as a key event that underlies neurodegeneration. Certain complement components are crucial instruments of widespread synapse loss because they can tag synapses with functional impairments leading to their engulfment by microglia. However, an exact understanding of the affected synaptic functions that predispose to complement-mediated synapse elimination is lacking. Therefore, we conducted systematic proteomic examinations on synaptosomes prepared from an amyloidogenic mouse model of Alzheimer's disease (APP/PS1). Synaptic fractions were separated according to the presence of the C1q-tag using fluorescence-activated synaptosome sorting and subjected to proteomic comparisons. The results raised the decline of mitochondrial functions in the C1q-tagged synapses of APP/PS1 mice based on enrichment analyses, which was verified using flow cytometry. Additionally, proteomics results revealed extensive alterations in the level of septin protein family members, which are known to dynamically form highly organized pre- and postsynaptic supramolecular structures, thereby affecting synaptic transmission. High-resolution microscopy investigations demonstrated that synapses with considerable amounts of septin-3 and septin-5 show increased accumulation of C1q in APP/PS1 mice compared to the wild-type ones. Moreover, a strong positive correlation was apparent between synaptic septin-3 levels and C1q deposition as revealed via flow cytometry and confocal microscopy examinations. In sum, our results imply that deterioration of synaptic mitochondrial functions and alterations in the organization of synaptic septins are associated with complement-dependent synapse loss in Alzheimer's disease.

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.

The use of oral appliances in obstructive sleep apnea: a retrospective cohort study spanning 14 years of private practice experience.

PURPOSE: In 2005, the American Academy of Sleep Medicine stated, "Oral appliances are indicated for use in patients with mild to moderate obstructive sleep apnea (OSA) who prefer them to CPAP therapy, or who do not respond to, are not appropriate candidates for, or who fail treatment attempts with CPAP." However, this recommendation is based upon variable results from only six studies with more than 100 participants. These studies have assessed the effectiveness of mandibular advancement devices (MADs) in specific groups (military populations, academic institutions, or hospital settings) with no large study conducted in a fee-for-service private practice where the majority of patients receive MADs for OSA. The purpose of this study is to report outcomes of a board-certified dental sleep practitioner managing mild, moderate, and severe OSA using customized titratable MADs. We hypothesize that patients will demonstrate a significant reduction in apnea-hypopnea index (AHI) scores after adjusting their customized titratable MADs. METHODS: This is a 14-year retrospective study design with pre- and post-treatment sleep studies. An AHI score < 10 respiratory events per hour with therapy is defined as treatment success. This study was performed by a single private practitioner. RESULTS: Of 2419 patient records analyzed, 544 (22%) had pre- and post-treatment sleep studies (89% polysomnograms). Of 510 patients with complete data, 459 (90%) revealed a decrease in AHI score < 10 respiratory events per hour indicating treatment success. Only 51 of these patients (10%) had a final AHI ≥ 10 and were considered treatment failures. Among the patients who lacked post overnight polysomnogram, 66/1921 (3%) discontinued the MAD due to adverse effects. Considering these patients as treatment failures as well, and therefore adding their number to the patients with complete sleep study data, the total treatment failures were 117/576 or 20%. Of the treatment successes, OSA was categorized by AHI at baseline as mild in 170 (34%), moderate in 181 (36%), and severe in 138 (28%). CONCLUSIONS: In patients with evaluable data, there was an 80% success rate for treatment of OSA using a custom-fabricated adjustable MAD including substantial numbers of patients with moderate and severe disease.

Metabolic Responses to a Battling Rope Protocol Performed in the Seated or Stance Positions.

Brewer, W, Kovacs, R, Hogan, K, Felder, D, and Mitchell, H. Metabolic responses to a battling rope protocol performed in the seated or stance positions. J Strength Cond Res 32(12): 3319-3325, 2018-The purpose of this study is to compare the levels of oxygen consumption and heart rate responses elicited by a treadmill or cycle V[Combining Dot Above]O2max test with a standing or sitting battling rope protocol (BRP) (treadmill vs. standing BRP) (cycle vs. seated BRP). Forty healthy subjects performed either a ramped V[Combining Dot Above]O2max treadmill or cycle test. At least 3 days later, the subjects who performed the ramped treadmill test did the standing BRP, and the subjects who performed the ramped cycle test did the sitting BRP. Each BRP consisted of 10 sets of 15/45 seconds of work/rest for 10 sets. V[Combining Dot Above]O2peak and HRpeak were recorded. Metabolic responses were significantly lower for the sitting BRP and standing as compared to the HRmax and V[Combining Dot Above]O2max values derived from the bicycle and treadmill tests. The BRP produced a V[Combining Dot Above]O2peak that was 71.87% (sitting) and 68.37% (standing) of the subjects' V[Combining Dot Above]O2max assessed u the bicycle and treadmill protocol. Moderate correlations were found between the V[Combining Dot Above]O2 during the seated (r = 0.61; p = 0.003) and standing (r = 0.43; p = 0.03) BRP and the bicycle and treadmill V[Combining Dot Above]O2max tests, respectively. The HRpeak elicited by the BRP performed in sitting (r = 0.52; p = 0.009) and standing (r = 0.67; p = 0.001) had a moderate correlation with the HRmax derived from the bicycle and treadmill tests. Battling ropes may be a low cost, accessible option to improve cardiovascular endurance for individuals who cannot stand or move their lower extremities in a rhythmic manner to conduct aerobic exercise.

Managing intra-EU mobility-do WHO principles of ethical recruitment have relevance?

BACKGROUND: The WHO Global Code of Practice on the International Recruitment of Health Personnel provides for guidance in health workforce management and cooperation in the international context. This article aims to examine whether the principles of the voluntary WHO Global Code of Practice can be applied to trigger health policy decisions within the EU zone of free movement of persons. METHODS: In the framework of the Joint Action on European Health Workforce Planning and Forecasting project (Grant Agreement: JA EUHWF 20122201 (see healthworkforce.eu)), focus group discussions were organised with over 30 experts representing ministries, universities and professional and international organisations. Ideas were collected about the applicability of the principles and with the aim to find EU law compatible, relevant solutions using a qualitative approach based on a standardised, semi-structured interview guide and pre-defined statements. RESULTS: Based on implementation practices summarised, focus group experts concluded that positive effects of adhering to the Code can be identified and useful ideas-compatible with EU law-exist to manage intra-EU mobility. The most relevant areas for intervention include bilateral cooperations, better use of EU financial resources, improved retention and integration policies and better data flow and monitoring. Improving retention is of key importance; however, ethical considerations should also apply within the EU. Compensation of source countries can be a solution to further elaborate on when developing EU financial mechanisms. Intra-EU circular mobility might be feasible and made more transparent if directed by tailor-made, institutional-level bilateral cooperations adjusted to different groups and profiles of health professionals. Integration policies should be improved as discrimination still exists when offering jobs despite the legal environment facilitating the recognition of professional qualifications. A system of feedback on registration/licencing data should be promoted providing for more evidence on intra-EU mobility and support its management. CONCLUSIONS: Workforce planning in EU Member States can be supported, and more equitable distribution of the workforce can be provided by building policy decisions on the principles of the WHO Code. Political commitment has to be strengthened in EU countries to adopt implementation solutions for intra-EU problems. Long-term benefits of respecting global principles of the Code should be better demonstrated in order to incentivise all parties to follow such long-term objectives.

Headcount and FTE data in the European health workforce monitoring and planning process.

BACKGROUND: Health workforce (HWF) planning and monitoring processes face challenges regarding data and appropriate indicators. One such area fraught with difficulties is labour activity and, more specifically, defining headcount and full-time equivalent (FTE). This study aims to review national practices in FTE calculation formulas for selected EU Member States (MS). METHODS: The research was conducted as a part of the Joint Action on European Health Workforce Planning and Forecasting. Definitions, categories and terms concerning the five sectoral professions were examined in 14 MS by conducting a survey. To gain a deeper understanding of the international data-reporting processes (Joint Questionnaire on Non-Monetary Health Care Statistics-JQ), six international expert interviews were conducted by using a semi-structured interview guide. RESULTS: Of the 14 investigated countries, four MS indicated that they report FTE to the JQ and that they also calculate FTE data for national planning purposes. The other countries do not use FTE data for national purposes, but most of them do use special calculations and/or estimation methods for converting headcount to FTE. The findings revealed significant differences between national calculation methods when reporting FTE data to the JQ. This diversity in terms of calculations and estimations can lead to biases with respect to international comparisons. This finding was reinforced by the expert interviews, since the experts agreed that the activities of healthcare professionals are a fundamental factor in HWF monitoring and planning. Experts underscored that activity should also be measured by FTE, and not only by headcount. CONCLUSIONS: FTE and headcount are significant factors in HWF planning and monitoring; therefore, national data collections should place emphasis on collecting data and calculating the appropriate indicators. National FTE could serve as a call to action for HWF planners due to the lack of matching international FTE data. At the international level, it is beneficial to monitor the trends and numbers regarding human resources and working time. For the moment, the exchange of information and mutual assistance for developing the capacity to apply common methodology could be a first step towards the standardisation of data collections.

[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.

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.

Effects of media stories of hope and recovery on suicidal ideation and help-seeking attitudes and intentions: systematic review and meta-analysis.

BACKGROUND: There is strong evidence that suicides increase after media stories about suicides by celebrities, particularly those that highlight the suicide method (the Werther effect). Much less is known about the Papageno effect-the protective effects of media stories of hope and recovery from suicidal crises. A synthesis of the retrievable evidence is lacking. We aim to summarise findings from randomised controlled trials about the effects of stories of hope and recovery on individuals with some degree of vulnerability to suicide. METHODS: For this systematic review and individual participant data meta-analysis, we searched PubMed (including MEDLINE), Scopus, Embase, PsycInfo, Web of Science, and Google Scholar published from inception to Sept 6, 2021, without language restrictions. We included trials that reported suicidal ideation (the primary outcome) or help-seeking attitudes or intentions (the secondary outcome) and tested a media narrative of hope and recovery. Studies were excluded if they did not feature a clearly positive story of hope and recovery, or had a control group exposed to suicide-related stimulus material. We contacted the lead or senior authors of all original studies to obtain participant-level data for this study. The primary analysis was restricted to individuals with some vulnerability to suicide. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomised trials. The study is registered with PROSPERO, number CRD42020221341. FINDINGS: Our search yielded 7347 records. 3920 records were screened by title and abstract, and 25 full-text records assessed for eligibility. There were eight eligible studies with 2350 participants for which individual participant data were sought. For suicidal ideation, six studies met the inclusion criteria for the primary analysis. Follow-up responses were available for 569 (90%) of 633 participants who were randomised with high vulnerability (345 [55%] allocated to the intervention group and 288 [45%] to the control group). The pooled standardised mean difference (SMD) indicated a small reduction in suicidal ideation of -0·22 (95% CI -0·39 to -0·04, p=0·017; six studies) in the intervention group. For help-seeking attitudes and intentions, four studies met the inclusion criteria and follow-up data were available for 362 (86%) of 420 participants (247 [59%] allocated to the intervention group and 173 [41%] to the control group). The pooled SMD showed no evidence of a difference between the groups (SMD=0·14, 95% CI -0·15 to 0·43, p=0·35; four studies). Low levels of cross-study heterogeneity effects were observed for both analyses (I2=5% [suicidal ideation] and I2=36% [help-seeking attitudes and intentions]). We found no evidence of publication bias. INTERPRETATION: Media narratives of hope and recovery from suicidal crises appear to have a beneficial effect on suicidal ideation in individuals with some vulnerability, but there is insufficient evidence regarding help-seeking attitudes and intentions. These findings provide new evidence about narratives for suicide prevention. FUNDING: None.

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.

Identification of Neuronal Pentraxins as Synaptic Binding Partners of C1q and the Involvement of NP1 in Synaptic Pruning in Adult Mice.

Elements of the immune system particularly that of innate immunity, play important roles beyond their traditional tasks in host defense, including manifold roles in the nervous system. Complement-mediated synaptic pruning is essential in the developing and healthy functioning brain and becomes aberrant in neurodegenerative disorders. C1q, component of the classical complement pathway, plays a central role in tagging synapses for elimination; however, the underlying molecular mechanisms and interaction partners are mostly unknown. Neuronal pentraxins (NPs) are involved in synapse formation and plasticity, moreover, NP1 contributes to cell death and neurodegeneration under adverse conditions. Here, we investigated the potential interaction between C1q and NPs, and its role in microglial phagocytosis of synapses in adult mice. We verified in vitro that NPs interact with C1q, as well as activate the complement system. Flow cytometry, immunostaining and co-immunoprecipitation showed that synapse-bound C1q colocalizes and interacts with NPs. High-resolution confocal microscopy revealed that microglia-surrounded C1q-tagged synapses are NP1 positive. We have also observed the synaptic occurrence of C4 suggesting that activation of the classical pathway cannot be ruled out in synaptic plasticity in healthy adult animals. In summary, our results indicate that NPs play a regulatory role in the synaptic function of C1q. Whether this role can be intensified upon pathological conditions, such as in Alzheimer's disease, is to be disclosed.

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.