Pre-conditioning of gingival epithelial cells with sub-apoptotic concentrations of curcumin prevents pro-inflammatory cytokine release.

BACKGROUND AND OBJECTIVE: Plaque-induced gingival inflammation (gingivitis) is ubiquitous in humans. The epithelial barrier reacts to the presence of oral bacteria and induces inflammatory cascades. The objective of this study was to investigate the mechanism by which the small molecule micronutrient curcumin could decrease inflammatory response in vitro to oral bacterium heat-killed Fusobacterium nucleatum as curcumin could be a useful compound for combatting gingivitis already consumed by humans. METHODS: H400 oral epithelial cell line was pre-conditioned with curcumin and the production of cytokines was measured by enzyme-linked immunosorbent assay (ELISA) and translocation of transcription factors was used to monitor inflammatory responses. Haem oxygenase (HO-1) expression and molecules that HO-1 releases were evaluated for their potential to reduce the quantity of cytokine production. Immunofluorescence microscopy and Western blotting were used to evaluate changes in transcription factor and enzyme location. RESULTS: Pre-conditioning of H400 cells with a sub-apoptotic concentration of curcumin (20 µM) attenuated secretion of Granulocyte-Macrophage - Colony-Stimulating Factor (GM-CSF) and reduced NFkB nuclear translocation. This pre-conditioning caused an increase in nuclear Nrf2; an initial drop (at 8 h) followed by an adaptive increase (at 24 h) in glutathione; and an increase in haem oxygenase (HO-1) expression. Inhibition of HO-1 by SnPPIX prevented the curcumin-induced attenuation of GM-CSF production. HO-1 catalyses the breakdown of haem to carbon monoxide, free iron and biliverdin: the HO-1/CO anti-inflammatory pathway. Elevations in carbon monoxide, achieved using carbon monoxide releasing molecule-2 (CORM2) treatment alone abrogated F. nucleatum-induced cytokine production. Biliverdin is converted to bilirubin by biliverdin reductase (BVR). This pleiotropic protein was found to increase in cell membrane expression upon curcumin treatment. CONCLUSION: Curcumin decreased inflammatory cytokine production induced by Fusobacterium nucleatum in H400 oral epithelial cells. The mechanism of action appears to be driven by the increase of haem oxygenase and the production of carbon monoxide.

Hepatitis B immunity among undergraduate nursing students: A brief report.

BACKGROUND: Health sciences students who report low/equivocal hepatitis B titers may be required to repeat the immunization series, even though the result may not indicate non-immunity. METHOD: To describe hepatitis B immunity patterns, this retrospective, descriptive study utilized de-identified vaccination records and anti-HBs titers of three cohorts of sophomore nursing students entering clinical rotations in 2018-2019. RESULTS: Only 33% of students had initial anti-HBs quantitative serum titer ≥10 mIU/ml, demonstrating immunity. After students with low/equivocal titers (n = 191, 64%) were re-immunized per institution protocol, only 2% (n = 7) were identified as non-responders. Cumulative costs incurred by students for revaccination and repeat titer exceeded $20,000, with a process time of up to 8 months. CONCLUSION: While rates of exposure to hepatitis B in acute care settings have steadily declined in the United States, students who go on to practice in community and public health settings have increased risk of exposure. Following best practices in demonstrating hepatitis B immunity, which include a single challenge dose followed by titer 4 weeks later, would decrease per student costs, wait time, and administrative burden associated with documentation and student counseling.

Rapid Transition to Online Learning for Baccalaureate Students: Teamwork During a Pandemic.

BACKGROUND: This article describes how a college of nursing (CON) converted its traditional undergraduate academic program to a 100% online program within 2 weeks of being informed of the need for curricular modifications due to the COVID-19 pandemic. METHOD: The college faculty met online prior to implementation to discuss student needs and special considerations. Clinical simulation experiences were developed based on International Association for Clinical Simulation and Learning (INACSL) standards and delivered through virtual simulation. RESULTS: Students evaluated the clinical simulation experiences in each course using Likert-style measures and reported positive experiences overall. Each cohort of students, including the May 2020 graduating seniors, successfully completed all of their classes for progression to the next semester or graduation. CONCLUSION: The successful conversion of traditional academic programs into a virtual environment requires leadership, collaboration, and teamwork. This CON had positive outcomes and offers lessons learned for future implementation. [J Nurs Educ. 2021;60(7): 397-399.].

Survival After Norwood Procedure in High-Risk Patients.

BACKGROUND: Multiple single-ventricle populations are noted to be at increased risk for mortality after the Norwood procedure. Preoperative risk factors include low birth weight, restrictive/intact atrial septum, obstructed pulmonary veins, ventricular dysfunction, and atrioventricular valve regurgitation. We report outcomes of the Norwood procedure in standard- and high-risk patients in the recent era. METHODS: All patients born with hypoplastic left heart syndrome between 2006 and 2016 who underwent a Norwood procedure at our institution were included. Patient data were retrospectively reviewed, and Kaplan-Meier analysis was used to evaluate survival between groups. RESULTS: The cohort included 177 patients. Fifty patients were determined high-risk preoperatively: low birth weight (n = 18), ventricular dysfunction/atrioventricular valve regurgitation (n = 13), intact or restrictive atrial septum/obstructed anomalous pulmonary venous return (n = 14), and multiple factors (n = 5). There were 2 (1.6%) deaths before Glenn in the standard-risk group, with a total of 10 (20%) from the high-risk groups (P < .0001). Survival at 1 year differed greatly between groups, with highest being standard risk at 89% and lowest in the intact septum/obstructed veins group at 54%. The difference between groups in long-term survival was significant (P < .001). CONCLUSIONS: Outcomes after the Norwood procedure have improved for standard-risk patients. Those with preoperative risk factors account for most of the early deaths after the Norwood procedure. This high-risk status does not resolve after Glenn, because longer-term survival continues to diverge from the standard-risk group.

Simulation-Based Interprofessional Education in a Rural Setting: The Development and Evaluation of a "Remote-In" Telehealth Scenario.

Simulation-based interprofessional education (IPE) is challenging to implement, especially on rural campuses. This article describes an innovative approach to IPE implementation using telehealth technology. Twenty-nine interdisciplinary students (nursing, pharmacy, and medical) participated in a simulation-based IPE scenario using a telehealth robot. Student experiences were evaluated using a mixed-methods approach. Surveys and video-recorded debriefing sessions revealed the majority of students felt the experience was superior to their previous IPE experiences, facilitated better understanding of disciplinary roles, and provided experience using telehealth tools. Programs considering this approach should have strong community partnerships, institutional support, and shared vision among key stakeholders.

Serum vitamin B12 is inversely associated with periodontal progression and risk of tooth loss: a prospective cohort study.

AIM: The aim of this study was to investigate the association of serum vitamin B12 with the progression of periodontitis and risk of tooth loss in a prospective cohort study. MATERIALS AND METHODS: In the Study of Health in Pomerania, 1648 participants were followed from 2002-2006 to 2008-2012 (mean duration 5.9 years). Serum vitamin B12 was measured by chemiluminescent enzyme immunoassay. Probing pocket depth (PD) and clinical attachment loss (CAL) were measured to reflect periodontal status on a half-mouth basis at each survey cycle. Tooth numbers are based upon a full-mouth tooth count. RESULTS AND CONCLUSIONS: In multivariate regression models, baseline vitamin B12 was inversely associated with changes in mean PD (Ptrend = 0.06) and mean CAL (Ptrend = 0.01), and risk ratios of tooth loss (TL; Ptrend = 0.006) over time. Compared to participants in the highest vitamin B12 quartile, those in the lowest quartile had 0.10 mm (95%CI: 0.03, 0.17; Pdifference = 0.007) greater increase in mean PD, 0.23 mm (95%CI: 0.09, 0.36; Pdifference = 0.001) greater increase in mean CAL and a relative risk of 1.57 (95%CI: 1.22, 2.03; Pdifference < 0.001) for TL. Stratified analyses showed stronger associations between vitamin B12 and changes in mean CAL among never smokers (Pinteraction = 0.058). Further studies are needed to understand the potential mechanisms of these findings.

Serum α-Tocopherol Has a Nonlinear Inverse Association with Periodontitis among US Adults.

BACKGROUND: Previous experimental models suggest that vitamin E may ameliorate periodontitis. However, epidemiologic studies show inconsistent evidence in supporting this plausible association. OBJECTIVE: We investigated the association between serum α-tocopherol (αT) and γ-tocopherol (γT) and periodontitis in a large cross-sectional US population. METHODS: This study included 4708 participants in the 1999-2001 NHANES. Serum tocopherols were measured by HPLC and values were adjusted by total cholesterol (TC). Periodontal status was assessed by mean clinical attachment loss (CAL) and probing pocket depth (PPD). Total periodontitis (TPD) was defined as the sum of mild, moderate, and severe periodontitis. All measurements were performed by NHANES. RESULTS: Means ± SDs of serum αT:TC ratio from low to high quartiles were 4.0 ± 0.4, 4.8 ± 0.2, 5.7 ± 0.4, and 9.1 ± 2.7 µmol/mmol. In multivariate regression models, αT:TC quartiles were inversely associated with mean CAL (P-trend = 0.06), mean PPD (P-trend < 0.001), and TPD (P-trend < 0.001) overall. Adjusted mean differences (95% CIs) between the first and fourth quartile of αT:TC were 0.12 mm (0.03, 0.20; P-difference = 0.005) for mean CAL and 0.12 mm (0.06, 0.17; P-difference < 0.001) for mean PPD, whereas the corresponding OR for TPD was 1.65 (95% CI: 1.26, 2.16; P-difference = 0.001). In a dose-response analysis, a clear inverse association between αT:TC and mean CAL, mean PPD, and TPD was observed among participants with relatively low αT:TC. No differences were seen in participants with higher αT:TC ratios. Participants with γT:TC ratio in the interquartile range showed a significantly lower mean PPD than those in the highest quartile. CONCLUSIONS: A nonlinear inverse association was observed between serum αT and severity of periodontitis, which was restricted to adults with normal but relatively low αT status. These findings warrant further confirmation in longitudinal or intervention studies.

Serendipity: a personal tale of two biographies, William Richard Gowers (1845-1915) and his son Ernest (1880-1966).

Between 2004 and 2012, the author wrote two biographies, the first of 20th century civil servant Ernest Gowers and the second of his father the Victorian neurologist William Richard Gowers. This article describes the author's experience conducting the research for two biographies at a time when the research tools available were rapidly shifting from paper-based to digital records. Technological aids have made the preliminary research of historians easier, but they have not taken the place of hard copy archive-based research. While the paper will focus primarily on the biography of William Richard Gowers, the author describes the research methods she employed to help reveal the personalities, strengths and weaknesses of both men, each of whom left his own intellectual legacy.

Feeding dysfunction in children with single ventricle following staged palliation.

OBJECTIVE: To determine the prevalence of feeding dysfunction in children with single ventricle defects and identify associated risk factors. STUDY DESIGN: Patients aged 2-6 years with single ventricle physiology presenting for routine cardiology follow-up at the Children's Hospital of Wisconsin were prospectively identified. Parents of the patients completed 2 validated instruments for assessment of feeding dysfunction. Chart review was performed to retrospectively obtain demographic and diagnostic data. RESULTS: Instruments were completed for 56 patients; median age was 39 months. Overall, 28 (50%) patients had some form of feeding dysfunction. Compared with a normal reference population, patients with single ventricle had statistically significant differences in dysfunctional food manipulation (P < .001), mealtime aggression (P = .002), choking/gagging/vomiting (P < .001), resistance to eating (P < .001), and parental aversion to mealtime (P < .001). Weight and height for age z-scores were significantly lower in subjects with feeding dysfunction (-0.84 vs -0.33; P < .05 and -1.46 vs -0.56; P = .001, respectively). Multivariable analysis identified current gastrostomy tube use (P = .02) and a single parent household (P = .01) as risk factors for feeding dysfunction. CONCLUSION: Feeding dysfunction is common in children with single ventricle defects, occurring in 50% of our cohort. Feeding dysfunction is associated with worse growth measures. Current gastrostomy tube use and a single parent household were identified as independent risk factors for feeding dysfunction.

Ascorbate and α-tocopherol differentially modulate reactive oxygen species generation by neutrophils in response to FcγR and TLR agonists.

Periodontitis, a ubiquitous chronic inflammatory disease, is associated with reduced antioxidant defences and neutrophil hyperactivity in terms of reactive oxygen species (ROS) generation. Its phenotype is thus characterized by oxidative stress. We have determined the effect of antioxidant micronutrients ascorbate and α-tocopherol on neutrophil ROS generation. Peripheral neutrophils from periodontally-healthy individuals (n = 20) were challenged with phorbol myristate acetate, IgG-opsonised Staphylococcus aureus, Fusobacterium nucleatum or PBS in the presence and absence of micronutrients (50 µM). Total and extracellular ROS were measured by luminol and isoluminol chemiluminescence respectively. Total and extracellular unstimulated, baseline ROS generation was unaffected by α-tocopherol, but inhibited by ascorbate and a combination of both micronutrients. Fcγ-receptor (Fcγ-R)-stimulated total or extracellular ROS generation was not affected by the presence of individual micronutrients. However, the combination significantly reduced extracellular FcγR-stimulated ROS release. Neither micronutrient inhibited TLR-stimulated total ROS, but the combination caused inhibition. Ascorbate and the micronutrient combination, but not α-tocopherol, inhibited extracellular ROS release by TLR-stimulated cells. Such micronutrient effects in vivo could be beneficial in reducing collateral tissue damage in chronic inflammatory diseases, such as periodontitis, while retaining immune-mediated neutrophil function.

William Gowers: the never completed third edition of the 'Bible of Neurology'.

William Gowers' classic single-authored two-volume A manual of diseases of the nervous system appeared in a first edition in 1886 and 1888, and in a second edition in 1892 and 1893, with a third edition of Volume 1 in 1899. No third edition of Volume 2 ever appeared. However, in 1949 Critchley stated that he had seen part of a revision of this volume. Subsequent writers could not find this material, but it recently came to light at Gowers' old hospital at Queen Square, London. The present paper describes the rediscovered material, containing Gowers' handwritten alterations for a further edition of Volume 2, and substantial new material, at least in relation to nystagmus and myasthenia. Gowers' declining health, or a conflict between his planned new text and his contributions to the neurology segments (1899) of Allbutt's System of medicine, may explain why a third edition of Volume 2 of the Manual of diseases of the nervous system never appeared.

В отношении каких стратегий профилактики суицида имеются фактические данные, подтверждающие их эффективность?

Суицид представляет собой одну из серьезных глобальных проблем общественного здравоохранения. Он связан с целым рядом различных факторов, таких как психическое заболевание, социальная изоляция, соматическое заболевание, злоупотребление психоактивными веществами, насилие в семье и доступ к средствам совершения самоубийства. Страны и регионы различаются между собой по эпидемиологическим показателям распространенности суицидов, причем в Восточной Европе эти показатели одни из самых высоких в мире. Несмотря на значительные усилия, предпринимаемые во многих странах, в том числе посредством принятия и осуществления специальных национальных планов, по-прежнему неясно, какие меры вмешательства дают наибольший эффект. Поэтому в предлагаемом докладе ставится цель синтезировать и обобщить результаты исследований, взятые из имеющихся систематических обзоров, с тем, чтобы дать ответ на два вопроса. Какие типы профилактических вмешательств оценивались в опубликованной литературе? В отношении каких стратегий имеются фактические данные высокого качества, подтверждающие их эффективность? Ограниченность фактических данных, а также значительные различия с точки зрения характеристик населения и ситуации в социальной, культурной и социально-экономической областях позволяют предположить, что нужно сочетать несколько подходов к профилактике, предусматривающих воздействие на разные факторы риска на разных уровнях. Кроме этого, осуществление любого нового вмешательства должно сопровождаться системой оценки его эффективности.

For which strategies of suicide prevention is there evidence of effectiveness?

Suicide is a serious global public health problem. It is associated with an array of factors, including mental illness, social isolation, physical illness, substance abuse, family violence and access to means of suicide. The epidemiology of suicide rates varies across countries and regions; those in eastern Europe are among the highest in the world. Despite substantial efforts in many countries, including through dedicated national plans, it remains unclear as to which interventions are the most effective. This report therefore aims to synthesize research findings from existing systematic reviews to address two questions. What types of preventive interventions have been evaluated in the published literature? Which strategies have good-quality evidence to support them? Limited evidence – as well as variability by population characteristics, social, cultural and socioeconomic situation – suggests that a combination of preventive approaches, addressing different risk factors at different levels, is required. In addition, an evaluation framework should accompany the implementation of any new intervention.

W R Gowers 1895: two unpublished post-graduate lectures.

On 10 May 1893, William Gowers began a series of weekly clinical demonstrations at the National Hospital for the Relief and Cure of the Paralysed and Epileptic at Queen Square, London. The contents of some of these demonstrations were published as 'Post-graduate Clinical Lectures' in the Clinical Journal, and in other learned periodicals. Some were also later included in his book Clinical Lectures on Diseases of the Nervous System. Recently, the manuscripts of what appear to be verbatim transcripts of two further but unpublished demonstrations from Gowers' course in 1895 came to light, one containing alterations made in Gowers' handwriting. The first concerned a case of disseminated sclerosis and its differentiation from hysterical paraplegia, the second transverse myelitis and its consequences for bladder function. Why these lectures were never published remains uncertain, but their relatively unedited contents reveal something of the neurological knowledge, diagnostic reasoning, clinical examination and teaching methods employed by one of the great pioneers of clinical neurology.

Mapping biological to clinical phenotypes during the development (21 days) and resolution (21 days) of experimental gingivitis.

AIM: To characterize and map temporal changes in the biological and clinical phenotype during a 21-day experimental gingivitis study. MATERIALS AND METHODS: Experimental gingivitis was induced over 21 days in healthy human volunteers (n = 56), after which normal brushing was resumed (resolution phase). Gingival and plaque indices were assessed. Gingival crevicular fluid was collected from four paired test and contra-lateral control sites in each volunteer during induction (Days 0, 7, 14 and 21) and resolution (Days 28 and 42) of experimental gingivitis. Fluid volumes were measured and a single analyte was quantified from each site-specific, 30s sample. Data were evaluated by analysis of repeated measurements and paired sample tests. RESULTS: Clinical indices and gingival crevicular fluid volumes at test sites increased from Day 0, peaking at Day 21 (test/control differences all p < 0.0001) and decreased back to control levels by Day 28. Levels of four inflammatory markers showed similar patterns, with significant differences between test and control apparent at Day 7 (substance P, cathepsin G, interleukin-1ß, elastase: all p < 0.03) and peaking at Day 21 (all p < 0.002). Levels of α-1-antitrypsin showed no pattern. CONCLUSIONS: Levels of substance P, cathepsin G, interleukin-1ß and neutrophil elastase act as objective biomarkers of gingival inflammation induction and resolution that typically precede phenotypical changes.

Perceptions and implications of violence from care home residents with dementia: a review and commentary.

AIMS AND OBJECTIVES: This paper presents a critical review of the literature related to the violence staff in care homes experience from people with dementia. It attempts to identify the psychological consequences abuse has on care workers and the implications this has for practice. BACKGROUND: Abuse in the form of violence or aggression against healthcare professionals is not new. However, when this is from residents with dementia in care homes it is considered to be part of the job. Consequently it is largely underreported and ignored which masks its true extent. CONCLUSION: The magnitude of violence in care homes crosses cultural boundaries. Fear of being blamed, job insecurity and resignation that abuse should be accepted as part of the job is unique to this care setting. The cumulative effect of psychological abuse leads to emotional exhaustion and depersonalisation which results in care workers emotionally and physically withdrawing from residents. Being subjected to abuse, feeling undervalued, unsupported and lacking essential skills may compromise a workforces' ability to provide person-centred care. A rising ageing population and prevalence of dementia will place demands on commissioners and providers to deliver high quality care. Consistent recording and reporting procedures, dementia specific training and infrastructures to support staff is therefore crucial.

Optimizing vesicourethral anastomosis healing after robot-assisted laparoscopic radical prostatectomy: lessons learned from three techniques in 1900 patients.

BACKGROUND AND PURPOSE: Creation of an optimally apposed, tension-free, well-supported vesicourethral anastomosis remains the cornerstone for anastomotic healing after radical prostatectomy. We report the effect of three techniques of bladder neck reconstruction during robot-assisted radical prostatectomy on anastomotic leak, stricture formation, and continence recovery. PATIENTS AND METHODS: Between January 2005 to September 2009, 1900 consecutive patients underwent robotic-assisted laparoscopic prostatectomy (RALP) by a single surgeon. Of these, the first 214 underwent vesicourethral conventional anastomosis (CA); the next 303 men underwent anterior reconstruction (AR) only; and last 1383 men underwent total anatomic restoration (TR). Data elements included patient age, body mass index, preoperative biopsy Gleason score and prostate-specific antigen level, prostate volume, total operative time, console time, time for performing vesicourethral anastomosis, estimated blood loss, tumor stage, and margin status on final pathologic findings. Primary end points were rates of clinically significant anastomotic leaks, bladder neck contractures, and time to return of continence. Chi-square and Fisher exact tests were used for analysis of categoric variables. The Cox proportional hazard model was used for both univariate and multivariate analysis. RESULTS: Clinically significant anastomotic leakage and bladder neck strictures were significantly fewer in the reconstructed groups (2.3% vs 1.0% vs 0.3% and 3.7% vs 1.3% vs 0.5% in the CA, AR, and TR groups, P < 0.01). Continence rates at 1, 6, 12, 26, and 52 weeks after RALP were also significantly better at all time points with AR and TR compared with CA alone (P < 0.001). CONCLUSIONS: TR of the continence mechanism optimizes vesicourethral anastomosis healing and hastens early continence return after RALP.

Proteomic analysis of a noninvasive human model of acute inflammation and its resolution: the twenty-one day gingivitis model.

The 21-day experimental gingivitis model, an established noninvasive model of inflammation in response to increasing bacterial accumulation in humans, is designed to enable the study of both the induction and resolution of inflammation. Here, we have analyzed gingival crevicular fluid, an oral fluid comprising a serum transudate and tissue exudates, by LC-MS/MS using Fourier transform ion cyclotron resonance mass spectrometry and iTRAQ isobaric mass tags, to establish meta-proteomic profiles of inflammation-induced changes in proteins in healthy young volunteers. Across the course of experimentally induced gingivitis, we identified 16 bacterial and 186 human proteins. Although abundances of the bacterial proteins identified did not vary temporally, Fusobacterium outer membrane proteins were detected. Fusobacterium species have previously been associated with periodontal health or disease. The human proteins identified spanned a wide range of compartments (both extracellular and intracellular) and functions, including serum proteins, proteins displaying antibacterial properties, and proteins with functions associated with cellular transcription, DNA binding, the cytoskeleton, cell adhesion, and cilia. PolySNAP3 clustering software was used in a multilayered analytical approach. Clusters of proteins that associated with changes to the clinical parameters included neuronal and synapse associated proteins.

Breathlessness clinics within specialist palliative care settings can improve the quality of life and functional capacity of patients with lung cancer.

This paper is a development on recent research that proved the value of non-pharmacological techniques and strategies in the management of breathlessness in lung cancer. It evaluates the intervention in a specialist palliative care setting using an outpatient clinic at Lewis-Manning House. Referrals were made by the patients' physician or specialist nurse. Patients (n = 30) were assessed and treated by the senior physiotherapist in charge of the clinic over three sessions. A number of outcomes were measured at various stages of the patients' treatment. The results have confirmed and strengthened the previous published results. Highly significant improvements in patients' breathlessness, functional capacity, activity levels and distress levels have been shown. For example, the percentage of patients experiencing breathlessness several times or more per day was reduced from 73% to 27% four weeks later. In addition, this project has been able to demonstrate significant improvements in quality of life and high levels of satisfaction with the interventions. Qualitative data enhanced the findings of objective measurements.