Impaired Periodontitis-Induced Cytokine Production by Peripheral Blood Monocytes and Myeloid Dendritic Cells in Patients with Rheumatoid Arthritis: A Case-Control Study.

Background: Immune cells from rheumatoid arthritis (RA) patients display a reduced in vitro response to Porphyromonas gingivalis (P. gingivalis), which may have functional immune consequences. The aim of this study was to characterize, by flow cytometry, the frequency/activity of monocytes and naturally occurring myeloid dendritic cells (mDCs) in peripheral blood samples from patients with periodontitis and patients with periodontitis and RA. Methods: The relative frequency of monocytes and mDCs in the whole blood, the frequency of these cells producing TNFα or IL-6 and the protein expression levels for each cytokine, before and after stimulation with lipopolysaccharide (LPS) from Escherichia coli plus interferon-γ (IFN-γ), were assessed by flow cytometry, in peripheral blood samples from 10 healthy individuals (HEALTHY), 10 patients with periodontitis (PERIO) and 17 patients with periodontitis and RA (PERIO+RA). Results: The frequency of monocytes and mDCs producing IL-6 or TNF-α and the expression of IL-6 and TNF-α in the PERIO group were generally higher. Within the PERIO+RA group, P. gingivalis and related antibodies were negatively correlated with the monocyte and mDC expression of IL-6. A subgroup of the PERIO+RA patients that displayed statistically significantly lower frequencies of monocytes producing IL-6 after activation presented statistically significantly higher peptidylarginine deiminase (PAD)2/4 activity, anti-arg-gingipain (RgpB) IgG levels, mean probing depth (PD), periodontal inflamed surface area (PISA) and bleeding on probing (BoP). Conclusions: In the patients with PERIO+RA, innate immune cells seemed to produce lower amounts of pro-inflammatory cytokines, which are correlated with worse periodontitis-related clinical and microbiological parameters.

How to teach students of medical and biological sciences electrophoresis in the spirit of physical chemistry - a laboratory exercise scenario.

Gel electrophoresis is one of the most important and most widely used tools in biomedical sciences. However, when students are acquainted with these techniques, information related to practical applications often neglects the physicochemical foundations of the occurring phenomena. The following article proposes a laboratory exercises scenario conducted in the problem-solving and decision-making strategies, which aims to familiarize beginner students with the physicochemical basis of electrophoresis in a simple and accessible way. By analyzing the scheme presented, students will gain knowledge of the basic sciences, as they will learn about the advantages and limitations of the method in addition to its applications. The experiments are designed in a way that allows students to draw conclusions about the parameters affecting the electrophoresis process and the sources of obvious errors. Moreover, the use of simple ionic dyes eliminates the need for complex apparatus and toxic reagents, which may be harmful. The main outcome of the class is to develop students' skill to design their own simple experiments using this commonly used technique.

Screening Tools for Obstructive Sleep Apnea in Pregnant Women: An Extended and Updated Systematic Review and Meta-analysis.

The prevalence of obstructive sleep apnea syndrome (OSA) increases in women during pregnancy and negatively affects maternal and fetal outcomes. The updated systematic review and meta-analysis aimed to evaluate the validity of the Berlin, STOP-Bang, and Epworth sleepiness scale (ESS) questionnaires in detecting OSA in pregnant women. PubMed, Embase, and Web of Science were searched systematically up to March 2022. After eligible studies inclusion, two independent reviewers extracted demographic and clinical data. Bivariate random effects models were used to estimate the pooled accuracy measures including sensitivity and specificity, positive (PPV) and negative predictive values (NPVs), diagnostic odds ratio (DOR), and receiver operating characteristic curve (ROC) curve. We included 8 studies including 710 pregnant women with suspected OSA. The performance values of Berlin, STOP-Bang, and ESS questionnaires were as follows: the pooled sensitivity were 61% (95% confidence interval (CI): 40%-80%), 59% (95% CI: 49%-69%), and 29%, (95% CI: 10%-60%); pooled specificity were 61% (95% CI: 42%-78%), 80% (95% CI: 55%-93%), and 80% (95% CI: 50%-94%); pooled PPVs were 60% (95% CI: 0.49-0.72), 73% (95% CI: 61%-85%), and 59% (95% CI: 31%-87%); pooled NPVs were 60% (95% CI: 0.49-0.71), 65% (95% CI: 54%-76%), and 53% (95% CI: 41%-64%); and pooled DORs were 3 (95% CI: 1-5), 6 (95% CI: 2-19), and 2 (95% CI: 1-3), respectively. It seems that the Berlin, STOP-Bang, and ESS questionnaires had poor to moderate sensitivity and specificity in pregnancy, with the ESS showing the worst characteristics. Further studies are required to evaluate the performance of alternative screening methods for OSA in pregnancy.

Association between a Recalled Positive Airway Pressure (PAP) Device and Incident Cancer: A Population-Based Study.

BACKGROUND: The real-world consequences of a Philips/Respironics recall for positive airway pressure (PAP) devices distributed between 2009 and 2021 are unknown. METHODS: We conducted a retrospective population-based study using health administrative databases (Ontario, Canada) on all new adult PAP users identified through the provincial funding system, free of cancer at baseline, who initiated (claimed) PAP treatment between 2012 and 2018. Everyone was followed from the PAP claim date to the earliest of incident cancer diagnosis, death, or the end of the follow-up (March 2022). We used inverse probability of treatment weighting to balance baseline characteristics between individuals on recalled devices and those on devices from other manufacturers. Weighted hazard ratios of incident cancer were compared between groups. RESULTS: Of 231 692 individuals identified, 58 204 (25.1%) claimed recalled devices, and 173 488 (74.9%) from other manufacturers. A meaningful baseline difference between groups (standardised difference≥0.10) was noted only by location-relevant covariates; other variables were mostly equally distributed (standardised differences≤0.06). Over a median follow-up of 6.3 years (IQR: 4.9-8.0), 11 166 (4.8%) developed cancer: unadjusted rates per 10 000 Person-Year (95 CI%) of 78.8 (76.0-81.7) in the recall group versus74.0 (72.4-75.6) in others (p=0.0034). Propensity score weighting achieved excellent balance in baseline characteristics between groups (standardised differences≤0.07). On a weighted sample, there was no statistical difference in the hazard of incident cancer between groups: cause-specific hazard ratio (recalled versus others) of 0.97, 95% CI: 0.89-1.06. CONCLUSION: In our real-world population study, compared to other manufacturers and adjusting for confounders, recalled devices do not appear to be independently associated with developing cancer.

Effectiveness and Safety of Etanercept in Paediatric Patients with Plaque-Type Psoriasis: Real-World Evidence.

Background: Psoriasis is a chronic, multisystemic, inflammatory disease affecting approximately 1% of children and significantly reducing their health-related quality of life. Etanercept is a biologic fusion protein-blocking TNF-α and belongs to one of the biologics used among the children population. The purpose of this study was to assess the effectiveness and safety profile of etanercept in paediatric patients with plaque-type psoriasis. Material and methods: The outcome of the treatment was evaluated based on Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and Children's Dermatology Life Quality Index (CDLQI). Achievement of at least PASI75 at week 16 was assessed as an adequate response to therapy, which was the primary endpoint. Results: Forty-three paediatric patients were included in the study, 24 females and 19 males. The average age at inclusion into our study was 13 years. At baseline, the mean PASI score, BSA, and CDLQI were 16.3 ± 6.5, 22.3 ± 12.2%, and 17.4 ± 5.3, respectively. At week 16, 90.7% of patients achieved PASI 50, 79.1% achieved PASI 75, and 46.5% attained PASI 90. There was also a decrease in mean BSA and CDLQI values to 3.5 ± 3.8 and 5.4 ± 5.7, respectively. Conclusions: Etanercept proved to be effective, safe, and well-tolerated among the paediatric population with psoriasis.

The Influence of ß-Carotene and Its Liposomal Form on the Expression of EMT Markers and Androgen-Dependent Pathways in Different Prostate Cell Lines.

Prostate cancer (PCa) is the most common malignancy in men. Although the prognosis in the early stages is good, the treatment of advanced PCa remains a formidable challenge. Even after an initial response to hormone therapy or chemotherapy, recurrences are frequent and resistance to any systemic treatment is common. ß-Carotene (BC), a plant-derived tetraterpene, is known for its antioxidant capacity and can modulate multiple cellular signaling pathways, potentially affecting androgen synthesis. We investigated the influence of BC (dissolved in EtOH/THF with a cell culture medium or encapsulated in liposomes (LP-BCs)) on the viability, migration potential, and connective tissue cleavage capabilities of several PCa cell lines (Du145, LNCaP, PC-3, and 22Rv1) and a healthy prostate model (RWPE cells). BC significantly reduced the proliferative capacity of all investigated cell lines at various concentrations (1.5-30 µM) and decreased cell migration. However, it significantly increased the expression of epidermal-mesenchymal transition (EMT) master proteins in all cancer cell lines and RWPE (p < 0.05) These effects were not observed with LP-BCs. This study suggests that LP-BCs, with their higher antiproliferative capabilities and pronounced inhibition of the EMT, may be a more effective form of possible PCa prevention or treatment than the free form. LPs may also modulate lipid metabolism in PCa cells.

The impact of periodontitis and periodontal treatment on rheumatoid arthritis outcomes: an exploratory clinical trial.

OBJECTIVE: Studies suggest rheumatoid arthritis (RA) patients could benefit from periodontal treatment. However, published data are inconsistent, and there is a need for better-controlled research. Our study aims to address these limitations. METHODS: In this exploratory randomised delayed-start study, 22 RA patients with moderate/severe periodontitis were subjected to full-mouth debridement. Periodontal and rheumatological assessments, including measuring anti-cyclic citrullinated peptide 2 (CCP2) IgG levels, were performed at baseline (V1), 2 months (V2) and 6 months (V3) after step 1 and 2 of periodontal therapy. Primary outcome was changes in disease activity score for 28 joints (DAS28) between V2 and V1. Secondary outcomes were changes in other rheumatological or periodontal clinical parameters (V2 or V3-V1). RESULTS: RA disease activity was significantly higher in RA patients with severe periodontitis compared to moderate periodontitis at baseline, with significant positive correlations between several rheumatological and periodontal parameters. After periodontal treatment, RA patients with severe, but not moderate, periodontitis demonstrated significant improvements in DAS28 (ΔV2-V1, p = 0.042; ΔV3-V1, p = 0.001) and significant reduction in anti-CCP2 IgG levels at V3 (p = 0.032). CONCLUSION: Periodontal treatment is locally effective in patients with RA and impacts RA disease activity and anti-CCP2 antibody levels in patients with severe periodontitis. Hence, our data suggest that periodontal assessment and treatment should be integrated in the management of RA patients within a treat-to-target strategy. CLINICAL TRIAL REGISTRATION: www.isrctn.com, ISRCTN 17950307.

Carbamylation Is Instrumental in End-Stage Kidney Disease Coagulopathies: The Impact on von Willebrand Factor and Platelet Functionality.

BACKGROUND: Chronic kidney disease (CKD) is a progressive, irreversible, and incurable condition characterized by high morbidity and mortality, affecting approximately one-tenth of the global population. Rise of urea-derived cyanate levels in CKD patients, severalfold higher in comparison to those found in healthy individuals, leads to an increased rate of carbamylation of lysine residues of proteins and peptides. This posttranslational modification plays an important role in the progression of kidney failure but also in the onset of CKD-related complications, including previously reported coagulopathies. In this study, we have explored the impact of carbamylation on the functionality of von Willebrand factor (vWF), a pivotal player in hemostasis, and its implications for platelet adhesion. MATERIALS AND METHODS: We have explored carbamylated vWF's interactions with its partner proteins via ELISA. Mass spectrometry was employed to identify modified lysine residues. Blood platelets isolated from healthy donors were carbamylated, and their activation, binding to endothelium and thromboxane release were evaluated using flow cytometry, adhesion assays and ELISA, respectively. RESULTS: Using mass spectrometry we detected the vWF's lysine residue smost susceptible to carbamylation. This modification has in turn affected vWF's interactions with its key binding partners: decreased binding to collagen types I/III but increased the affinity to factor FVIII, while its binding to fibrinogen remained unchanged. Carbamylation of vWF impeded vWF-blood platelet binding, but carbamylation of platelets led to their increased thrombin-dependent activation as observed by enhanced phosphatidylserine exposure, improved their binding to vascular endothelium, at the same time decreasing the production of the prothrombotic mediator, thromboxane A2. CONCLUSION: Our findings highlight the multifaceted impact of carbamylation on vWF and platelets, disturbing the delicate balance of coagulation cascade. These alterations could contribute to the complex hemostatic imbalance in ESKD, underscoring the need for further research to fully understand these mechanisms and their clinical implications.

Prevalence and regional distribution of obstructive sleep apnea in Canada: Analysis from the Canadian Longitudinal Study on Aging.

OBJECTIVES: Obstructive sleep apnea (OSA) is a common chronic condition that is often undiagnosed or diagnosed after many years of symptoms and has an impact on quality of life and several health factors. We estimated the Canadian national prevalence of OSA using a validated questionnaire and physical measurements in participants in the Canadian Longitudinal Study on Aging (CLSA). METHODS: The method used individual risk estimation based upon the validated STOP-BANG scale developed for OSA. This stratified population sample spans Canada to provide regional estimates. RESULTS: In this sample of adults aged 45 to 85 years old, the overall prevalence in 2015 of combined moderate and severe OSA in the 51,337 participants was 28.1% (95% confidence intervals, 27.8‒28.4). The regional prevalence varied statistically between Atlantic Canada and Western Canada (p < 0.001), although clinically the variations were limited. The provincial prevalence for moderate and severe OSA ranged from 27.5% (New Brunswick and British Columbia) to 29.1% (Manitoba). Body mass index (BMI) was the dominant determinant of the variance between provinces (ß = 0.33, p < 0.001). Only 1.2% of participants had a clinical diagnosis of OSA. CONCLUSION: The great majority (92.9%) of the participants at high risk of OSA were unrecognized and had no clinical diagnosis of OSA.

RéSUMé: OBJECTIFS: Le syndrome de l'apnée du sommeil (SAS) est une maladie chronique courante qui est souvent non diagnostiquée ou diagnostiquée plusieurs années après l'apparition de symptômes et qui a un impact sur la qualité de vie ainsi que plusieurs autres facteurs de santé. Nous avons estimé la prévalence nationale canadienne du SAS à l'aide d'un questionnaire validé et de mesures physiques chez les participants de l'Étude longitudinale canadienne sur le vieillissement (ÉLCV). MéTHODES: L'étude mesure l'estimation du risque individuel du SAS basée sur l'échelle validée STOP-BANG qui a été développée pour l'évaluation du SAS. Cet échantillon de population stratifié couvre tout le Canada et permet de fournir des estimations régionales. RéSULTATS: Dans cet échantillon d'adultes âgés de 45 à 85 ans, la prévalence globale du SAS modéré et sévère chez les 51 337 participants était de 28,1 % en 2015 (intervalles de confiance à 95 %: 27,8‒28,4). La prévalence régionale variait statistiquement entre le Canada atlantique et l'ouest du Canada (p < 0,001), bien que les variations cliniques soient limitées. La prévalence provinciale du SAS modéré et sévère variait entre 27,5 % (Nouveau-Brunswick et Colombie-Britannique) et 29,1 % (Manitoba). L'indice de masse corporelle représentait le facteur dominant de la variance entre les provinces (ß = 0,33, p < 0,001). Seulement 1,2 % des participants avaient un diagnostic clinique du SAS. CONCLUSION: La grande majorité (92,9 %) des participants présentant un risque élevé du SAS n'étaient pas identifiés auparavant et n'avaient aucun diagnostic clinique du SAS.

Dimethyl Sulfoxide (DMSO) as a Potential Source of Interference in Research Related to Sulfur Metabolism-A Preliminary Study.

Dimethyl sulfoxide (DMSO), an organosulfur compound, is widely used as the gold standard solvent in biological research. It is used in cell culture experiments and as a component of formulations in in vivo studies. Unfortunately, parameters related to sulfur metabolism are often not taken into account when using DMSO. Therefore, in this work we aim to show that the addition of DMSO to the culture medium (even in amounts commonly considered acceptable) alters some parameters of sulfur metabolism. For this study, we used three cell lines: a commercially available Caco-2 line (HTB-37, ATCC) and two lines created as part of our early studies (likewise previously described in the literature) to investigate the anomalies of sulfur metabolism in mucopolysaccharidosis. As the negative effects of DMSO on the cell membrane are well known, additional experiments with the partial loading of DMSO into polymerosomes (poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide), PEG-PLGA) were performed to eliminate these potentially disruptive effects. The results show that DMSO is a source of interference in studies related to sulfur metabolism and that there are not just simple effects that can be corrected in the final result by subtracting control values, since complex synergisms are also observed.

Comparison of Sleep Apnea Questionnaires and Reported Diagnosis in Neurological Disorders of Aging.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with worse outcomes in stroke, Alzheimer's disease (AD) and Parkinson's disease (PD), but diagnosis is challenging in these groups. We aimed to compare the prevalence of high risk of OSA based on commonly used questionnaires and self-reported OSA diagnosis: 1. within groups with stroke, AD, PD and the general population (GP); 2. Between neurological groups and GP. METHODS: Individuals with stroke, PD and AD were identified in the Canadian Longitudinal Study of Aging (CLSA) by survey. STOP, STOP-BAG, STOP-B28 and GOAL screening tools and OSA self-report were compared by the Chi-squared test. Logistic regression was used to compare high risk/self-report of OSA, in neurological conditions vs. GP, adjusted for confounders. RESULTS: We studied 30,097 participants with mean age of 62.3 years (SD 10.3) (stroke n = 1791; PD n = 175; AD n = 125). In all groups, a positive GOAL was the most prevalent, while positive STOP was least prevalent among questionnaires. Significant variations in high-risk OSA were observed between different questionnaires across all groups. Under 1.5% of individuals self-reported OSA. While all questionnaires suggested a higher prevalence of OSA in stroke than the GP, for PD and AD, there was heterogeneity depending on questionnaire. CONCLUSIONS: The wide range of prevalences of high risk of OSA resulting from commonly used screening tools underscores the importance of validating them in older adults with neurological disorders. OSA was self-reported in disproportionately small numbers across groups, suggesting that OSA is underdiagnosed in older adults or underreported by patients, which is concerning given its increasingly recognized impact on brain health.

Exploring obstructive sleep apnea and sleep architecture in Parkinson's disease motor subtypes.

INTRODUCTION: Parkinson's disease (PD) can be divided into motor subtypes: postural instability/gait difficulty (PIGD), tremor dominant, and indeterminate. This study aimed to assess differences in sleep structure and obstructive sleep apnea (OSA) between the PIGD and non-PIGD subtypes. METHODS: PD participants with or without OSA (defined as apnea-hypopnea index (AHI) ≥ 15 events/hour on overnight polysomnography) were included. Patients were separated into two groups: PIGD and non-PIGD. Linear regression was used to explore differences in sleep, AHI, and other respiratory parameters between groups (adjusted for variables determined a priori). Logistic regression adjusted for the same variables was used to determine if the proportion of patients with OSA differed across groups. Subset analyses were performed: subset 1 excluding patients on psychoactive medication; subset 2 excluding patients taking levodopa or dopaminergic agonists (DAs) at nighttime and subset 3 excluding patients on either of the abovementioned drugs. RESULTS: 146 participants were studied. The non-PIGD group had less N3 sleep compared to the PIGD group (12.4% vs 16.9% p = 0.06), reaching significance in subsets 1 and 3. The AHI was significantly lower in the PIGD group (p = 0.047), including when medication effects were removed (p < 0.05). OSA was more frequent in the non-PIGD group, but only significantly in subset 3 (adjusted OR 0.3, p = 0.04). CONCLUSION: OSA may be more severe in non-PIGD subtypes, and more frequent, in a subset free of psychoactive medication, and of levodopa and DAs, possibly owing to motor complications and dyskinesia. Future studies are required to confirm this.

Sleep spindle density and temporal clustering are associated with sleep-dependent memory consolidation in Parkinson's disease.

STUDY OBJECTIVES: Sleep is required for successful memory consolidation. Sleep spindles, bursts of oscillatory activity occurring during non-rapid eye movement sleep, are known to be crucial for this process and, recently, it has been proposed that the temporal organization of spindles into clusters might additionally play a role in memory consolidation. In Parkinson's disease, spindle activity is reduced, and this reduction has been found to be predictive of cognitive decline. However, it remains unknown whether alterations in sleep spindles in Parkinson's disease are predictive of sleep-dependent cognitive processes such as memory consolidation, leaving open questions about the possible mechanisms linking sleep and a more general cognitive state in Parkinson's patients. METHODS: The current study sought to fill this gap by recording overnight polysomnography and measuring overnight declarative memory consolidation in a sample of 35 patients with Parkinson's. Memory consolidation was measured using a verbal paired-associates task administered before and after the night of recorded sleep. RESULTS: We found that lower sleep spindle density at frontal leads during non-rapid eye movement stage 3 was associated with worse overnight declarative memory consolidation. We also found that patients who showed less temporal clustering of spindles exhibited worse declarative memory consolidation. CONCLUSIONS: These results suggest alterations to sleep spindles, which are known to be a consequence of Parkinson's disease, might represent a mechanism by which poor sleep leads to worse cognitive function in Parkinson's patients. CITATION: Lahlou S, Kaminska M, Doyon J, Carrier J, Sharp M. Sleep spindle density and temporal clustering are associated with sleep-dependent memory consolidation in Parkinson's disease. J Clin Sleep Med. 2024;20(7):1153-1162.

Home Noninvasive Ventilation in COPD.

Evidence is increasing that long-term noninvasive ventilation (LTNIV) can improve outcomes in individuals with severe, hypercapnic COPD. Although the evidence remains unclear in some aspects, LTNIV seems to be able to improve patient-related and physiologic outcomes like dyspnea, FEV1 and partial pressure of carbon dioxide (Pco2) and also to reduce rehospitalizations and mortality. Efficacy generally is associated with reduction in Pco2. To achieve this, an adequate interface (mask) is essential, as are appropriate ventilation settings that target the specific respiratory physiologic features of COPD. This will ensure comfort, synchrony, and adherence that will result in physiologic improvements. This article briefly reviews the newest evidence and current guidelines on LTNIV in severe COPD. It describes an actual patient who benefitted from the therapy. Finally, it provides strategies for initiating and optimizing this LTNIV in COPD, discussing high-pressure noninvasive ventilation, optimization of triggering, and control of inspiratory time. As demand increases, clinicians will need to be familiar with this therapy to reap its benefits, because inadequately adjusted LTNIV will not be tolerated or effective.

Searching for EGF Fragments Recreating the Outer Sphere of the Growth Factor Involved in Receptor Interactions.

The aims of this study were to determine whether it is possible to use peptide microarrays obtained using the SPOT technique (immobilized on cellulose) and specific polyclonal antibodies to select fragments that reconstruct the outer sphere of proteins and to ascertain whether the selected peptide fragments can be useful in the study of their protein-protein and/or peptide-protein interactions. Using this approach, epidermal growth factor (EGF) fragments responsible for the interaction with the EGF receptor were searched. A library of EGF fragments immobilized on cellulose was obtained using triazine condensing reagents. Experiments on the interactions with EGFR confirmed the high affinity of the selected peptide fragments. Biological tests on cells showed the lack of cytotoxicity of the EGF fragments. Selected EGF fragments can be used in various areas of medicine.

Long term effects of continuous positive airway pressure treatment of obstructive sleep apnea-hypopnea syndrome in multiple sclerosis patients.

BACKGROUND: Obstructive sleep apnea-hypopnea (OSAH) is common in MS patients and is associated with fatigue. We recently published a randomized, controlled trial (RCT) of active vs sham continuous positive airway pressure (CPAP) treatment in MS patients with fatigue, poor sleep quality, and (OSAH) (Mult Scl J 2022;28:82-92). Our aim was to evaluate the long-term effects of CPAP treatment on fatigue (Fatigue Severity Scale, FSS, primary outcome) and other clinical outcomes in MS patients with OSAH. METHODS: Following the RCT, participants were offered treatment with CPAP and participation in an open label study. Patients were re-evaluated with RCT outcome measures at least 6 months after completion of the RCT. RESULTS: Twenty-eight of 34 (82 %) RCT-completers participated in this study a mean of 2.7 years after the RCT. Sixteen (57 %) patients were treated with CPAP (mean use 5.4 ± 1.0 h/night during the 6 months prior to follow-up visit), while the other 12 patients declined CPAP use and received no other OSAH treatments. Baseline clinical characteristics, including MS related disability and sleep outcomes, were not significantly different between CPAP-treated vs non-CPAP treated patients. Patients using CPAP at follow-up (n = 16) demonstrated significant improvements from RCT baseline in FSS (p = 0.005), Fatigue Scale for Motor and Cognitive Functions (p = 0.008, p = 0.012), Pittsburgh Sleep Quality Index (p = 0.016), Center of Epidemiological Studies-Depression Scale (p = 0.05), and Multiple Sclerosis Quality of Life-54 (MSQOL-54) physical and mental component scores (p = 0.012, p = 0.023), but no improvements in Epworth Sleepiness Scale, Pain Visual Analog Scale, or Expanded Disability Status Scale. Patients not using CPAP (n = 12) had no significant improvements in outcome measures. Using a linear mixed model, FSS (p = 0.03), morning fatigue (p = 0.048), and MSQOL-54 physical component score (p = 0.02) improved significantly in CPAP treated patients compared with non-CPAP treated patients from RCT baseline. CONCLUSION: In this post-RCT open label study, long-term CPAP use was associated with improved fatigue (FSS, our primary outcome) and physical quality of life in MS patients with OSAH.

Differences in nonoxidative sulfur metabolism between normal human breast MCF-12A and adenocarcinoma MCF-7 cell lines.

Recent studies have revealed the role of endogenous hydrogen sulfide (H2S) in the development of breast cancer. The capacity of cells to generate H2S and the activity and expression of the main enzymes (cystathionine beta synthase; CBS, cystathionase γ-lyase; CGL, 3-mercaptopyruvate sulfurtransferase; MPST and thiosulfate sulfurtransferase; TST) involved in H2S metabolism were analyzed using an in vitro model of a non-tumourigenic breast cell line (MCF-12A) and a human breast adenocarcinoma cell line (MCF-7). In both cell lines, MPST, CGL, and TST expression was confirmed at the mRNA (RT-PCR) and the protein (Western Blot) level, while CBS expression was detected only in MCF-7 cells. Elevated levels of GSH, sulfane sulfur and increased CBS and TST activity were presented in the MCF-7 compared to the MCF-12A cells. It appears that cysteine might be mainly a substrate for GSH synthesis in breast adenocarcinoma. Increased capacity of the cells to generate H2S was shown for MCF-12A compared to MCF-7 cell line. Results suggest an important function of CBS in H2S metabolism in breast adenocarcinoma. The presented work may contribute to further research on new therapeutic possibilities for breast cancer - one of the most frequently diagnosed types of cancer among women.

Noninvasive Home Mechanical Ventilation for Stable Hypercapnic COPD: A Clinical Respiratory Review from Canadian Perspectives.

Acute short-term noninvasive ventilation (NIV) for hypercapnic respiratory failure in chronic obstructive pulmonary disease (COPD) has well-established benefits; however, the role of long-term home NIV remains controversial. In the past decade, studies utilizing aggressive NIV settings to maximally reduce carbon dioxide levels (PaCO2) have resulted in several positive clinical trials and led to updated guidelines on home NIV for stable hypercapnic COPD patients. This clinical respiratory review discusses the high-intensity NIV approach, summarizes recent key trials and guidelines pertaining to home NIV in COPD, and considers key clinical questions for future research and application in the Canadian context. With recent evidence and Canadian Thoracic Society (CTS) guidelines supporting the use of NIV in carefully selected COPD patients with persistent daytime hypercapnia, we believe it is time to reconsider our approach.