[Diagnosis and Treatment in frontobasal fractures]. / Vorgehen bei frontobasalen Frakturen.

Traumatic brain injury can result in frontobasal fractures (FBF). The goals of treatment for FBF are to eliminate primary morbidity and/or prevent secondary morbidity. Of particular importance in this regard is the proximity of important sensory organs for hearing, vision, smell, and taste, as well as their supplying nervous structures. Medical history, clinical findings, or CT scan are necessary and should lead to an individual evaluation. Depending on the severity of the fractures, the following disciplines may be involved in the treatment of FBF: neurosurgery, plastic surgery, oral and maxillofacial surgery, and/or otorhinolaryngology. Particularly less invasive endoscopic endonasal therapy is a specialty of otorhinolaryngologic surgeons and has not been widely established in other disciplines. The present work provides an overview of the current state of the art in terms of the following aspects, taking into account the current literature: anatomic principles, classification of fractures, diagnostics (in particular clinical examination, imaging, and laboratory chemistry tests), clinical symptoms, and treatment.

Comparison of Psychological and Physiological Stress in NICU Nurses: Effects of Unit Design and Shift.

BACKGROUND: Effects of unit design and shift worked on stress in neonatal intensive care unit (NICU) nurses have not been fully studied. PURPOSE: To compare stress in NICU nurses who work in single-family room (SFR) or open bay (OBY) units and on nonrotating day or night shift. METHODS: Full-time registered nurses (RNs) (n = 72) from a 42-bed SFR and a 131-bed OBY NICU participated in this comparative cross-sectional study. The Nurse Stress Scale (NSS) and within-shift repeated salivary cortisol levels were used to measure stress. The relationship between NSS score and salivary cortisol level was examined using multiple linear regression. Salivary cortisol levels of day versus night shift were compared with mixed-effects linear models. RESULTS: NSS scores were similar for SFR and OBY units (P = .672) and day versus night shift (P = .606). Changes in cortisol level over time (P = .764) and final cortisol level (P = .883) for SFR versus OBY were not significantly different after controlling for shift. Salivary cortisol level of day-shift nurses decreased significantly over time compared with night-shift nurses (P < .001). The final cortisol level was significantly higher for night-shift compared with day-shift nurses (P < .001). IMPLICATIONS FOR PRACTICE: Psychological (NSS) and physiologic (salivary cortisol) stress of NICU nurses is similar in established SFR and OBY units. Cortisol levels are higher at the end of shift in nurses who work night shift and may reflect increased physiologic stress. IMPLICATIONS FOR RESEARCH: Strategies are needed for reducing stress in NICU nurses who work night shift.

Influence of travel burden on tumor classification and survival of head and neck cancer patients.

PURPOSE: Cancer patients have to overcome various barriers to obtain diagnostics and treatment at head and neck cancer centers. Travel distance to a specialized hospital may result in psychosocial and financial distress, thus interfering with diagnostics, treatment, and follow-up care. In this study, we have aimed to analyze the association of travel distance with cTNM status, UICC stage at primary diagnosis, and survival outcomes of head and neck cancer (HNC) patients. METHODS: We have analyzed data of 1921 consecutive HNC patients diagnosed between 2014 and 2019 at the head and neck cancer center of the Comprehensive Cancer Center Ulm (CCCU), Germany. Postal code-based travel distance calculation in kilometers, TNM status, and UICC stage were recorded at initial diagnosis. The assembly of travel distance-related groups (short, intermediate, long-distance) has been investigated. Moreover, group-related survival and recurrence analysis have been performed. RESULTS: In contrast to observations from overseas, no association of travel distance and higher cTNM status or UICC stage at primary diagnosis has been observed. Furthermore, no significant differences for recurrence-free survival and overall survival by travel distance were detected. CONCLUSION: In southern Germany, travel distance to head and neck cancer centers seems to be tolerable. Travel burden is not synonymous with travel distance alone but also involves sociodemographic, monetary, and disease-specific aspects as well as accessibility to proper infrastructure of transport and health care system.

[Tumor biology of oropharyngeal carcinoma]. / Tumorbiologie des Oropharynxkarzinoms.

BACKGROUND: Etiologically, oropharyngeal squamous cell carcinoma (OPSCC) can be divided into OPSCC caused by noxious agents and human papillomavirus (HPV)-driven carcinoma. These types differ with regard to clinical features and prognosis-differences which are rooted in the underlying molecular biology of the tumor. OBJECTIVE: The aim of this work is to provide an overview of the molecular biological characteristics of the genetics, epigenetics, and immunology of OPSCC. MATERIALS AND METHODS: A literature review was performed on a selection of genetic, epigenetic, and immunological factors characterizing OPSCC. RESULTS: The understanding of genetic aberrations and their consequences for cancerogenesis and tumor biology is increasing. Epigenetic phenomena are complementing functional relationships. However, epigenetic mechanisms of gene regulation are complex and much research is still required in this field. Immunological aspects of cancer molecular biology have moved into the focus in light of recent advances in the field of immunotherapy. CONCLUSION: The tumor biology of OPSCC is primarily defined by its HPV status. Additionally, HPV-independent genetic, epigenetic, and immunological signatures are being defined. From these advances, rationales for new treatment concepts may evolve.

NDUFA9 point mutations cause a variable mitochondrial complex I assembly defect.

Mitochondrial respiratory chain complex I consists of 44 different subunits and contains 3 functional modules: the Q-, the N- and the P-module. NDUFA9 is a Q-module subunit required for complex I assembly or stability. However, its role in complex I biogenesis has not been studied in patient fibroblasts. So far, a single patient carrying an NDUFA9 variant with a severe neonatally fatal phenotype has been reported. Via exome sequencing, we identified a novel homozygous NDUFA9 missense variant in another patient with a milder phenotype including childhood-onset progressive generalized dystonia and axonal peripheral neuropathy. We performed complex I assembly analysis using primary skin fibroblasts of both patients. Reduced complex I abundance and an accumulation of Q-module subassemblies were present in both patients but more pronounced in the severe clinical phenotype patient. The latter displayed additional accumulation of P-module subassemblies, which was not present in the milder-phenotype patient. Lentiviral complementation of both patient fibroblast cell lines with wild-type NDUFA9 rescued complex I deficiency and the assembly defects. Our report further characterizes the phenotypic spectrum of NDUFA9 deficiency and demonstrates that the severity of the clinical phenotype correlates with the severity of the effects of the different NDUFA9 variants on complex I assembly.

Suture material use and procurement: an audit of a public hospital surgical system in Gauteng, South Africa.

BACKGROUND: Surgical systems are integral to successful, safe and cost effective clinical practice and must balance surgical demands on consumable items and their costs. Suture material is a key consumable resource, and was evaluated in an audit of consumable use and cost as well as the procurement systems within the South African Gauteng public health care sector. AIMS: To determine suture use and cost in the four commonest general surgical procedures - abdominal wall closure, mastectomy, appendicectomy and inguinal hernia repair - in three academic Gauteng hospitals. Performance and availability were evaluated as a secondary aim in suture material use. METHOD: A prospective observational study. Suture use was documented by the surgeon at the time of the procedure and qualitative investigation at relevant hospital departments determined suture material procurement and expenditure. RESULTS: The surgeons in three facilities documented consistent material type and average number of units used; however, in some cases there was a lack of availability of appropriate material and breakage of generic material intraoperatively. There is no consistent and consolidated electronic record-keeping of suture stock and cost in all three hospitals, therefore cost of suture material used was not obtainable. CONCLUSION: Clinical deficiencies in availability and quality of material may have adverse implications for patient health, healthcare costs and budgets through procedure-related complications and should be investigated. There is a lack of communication between the financial management, procurement officers, hospital and theatre stores and theatre staff. It is suggested that clinical protocols and system-based strategies be put in place to manage surgical consumables.

Care of 500-1500 Gram Premature Infants in Hybrid Incubators.

BACKGROUND: Although technological advances have improved devices used to maintain the temperatures of 500- to 1500-g infants, managing the thermal environment remains challenging. PURPOSE: To evaluate the effects of 2 methods of thermal support provided by a hybrid incubator during routine care in the first week of life. METHODS: This descriptive, comparative study evaluates changes in temperature, humidity, heart rate, and oxygen saturation in the incubator versus radiant warmer (canopy) modes of hybrid warmers using data downloaded from the incubator and the monitor. The impact of the Boost Curtain on temperature when opening the portholes during the incubator mode was also examined. Mixed-effects linear models and the log-rank test were used to analyze patient data to determine the effect of thermal support on temperature and humidity changes during care, as well as during the postcare period. RESULTS: Entering the incubator through the portholes improved temperature control compared with using the canopy mode. The Boost Curtain resulted in an overall temperature stability and heat gain. IMPLICATIONS FOR PRACTICE: Nurses caring for premature infants in hybrid incubators should minimize incubator openings and utilize portholes rather than the canopy whenever practical. The Boost Curtain should be used when opening the portholes during the incubator mode. IMPLICATIONS FOR RESEARCH: Comparing time, accuracy, and tolerance of procedures in the canopy versus incubator modes would improve nurses' ability to determine the best approach for different clinical scenarios.

[Stigma of mental illness among students]. / Stigmatisierung psychischer Erkrankung unter Schülern.

BACKGROUND: Social stigma connected to mental illness is a societal problem for which we lack data, especially among children and teenagers. OBJECTIVES: The purpose of this study was to assess how adolescents stigmatize mental illness in peers and to investigate if stigmatizing attitudes differed as a function of other variables (e. g. age, gender, level of education). MATERIALS AND METHODS: A German translation of the Revised Attribution Questionnaire (r-AQ), a nine-item survey, was administered to 246 pupils between 14 and 16 years of age, who were recruited from seven German schools. RESULTS: The pupils investigated in the study scored in the non-stigmatizing range of the questionnaire. Demographic factors did not have a significant effect on their stigmatizing attitude. CONCLUSIONS: The low stigmatizing tendencies can be explained by existing contact with the mentally ill or by possible effects of recruitment. Future research should take knowledge about mental illness as a possible factor influencing stigmatizing attitudes into account.

Do iatrogenic serosal injuries result in small bowel perforation in a rabbit model?

BACKGROUND: Surgical dogma dictates that serosal injuries should be repaired during laparotomy as these injuries may result in localised areas of bowel ischaemia and may perforate. No study has investigated whether there is a correlation between the extent of serosal injuries and the risk for perforation under normal physiological conditions. We hypothesized that small bowel serosal injuries do not result in early or late perforation at physiological intraluminal pressures regardless of their size. METHOD: An in-vivo rabbit small bowel serosal injury model was developed and two experiments were conducted. The first - to determine whether and at which pressures various lengths and circumferences of serosal injuries in small bowel result in immediate bowel perforation - was performed infusing saline into isolated bowel segments with or without a variety of serosal injuries. In the second study - to determine whether or not serosal injuries result in delayed perforation - a range of injuries was created in rabbits and the effect assessed at re-laparotomy 5 days after the creation of the injury. RESULTS: No perforations were observed at the site of serosal injuries at physiological intraluminal pressures. Perforations occurred at 43.7+ 18.6 cmH2O, 23.3+ 14.4 cmH2O, and 24.4+ 23.9 cmH2O for controls, 4 cm long and 100% circumference serosal injuries respectively (p-value = 0.18 for various lengths and 0.71 for various circumferences). No serosal injuries perforated within 72 or 120 hours after creation. CONCLUSION: Small bowel serosal injuries do not perforate or leak at physiological intraluminal pressures, either at the time of creation or up to 120 hours thereafter.

A 20-year population-based study on the epidemiology, clinical features, treatment, and outcome of nodular lymphocyte predominant Hodgkin lymphoma.

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a subtype of Hodgkin lymphoma characterized by a unique clinical and histological presentation. Because of the rare nature of this disease, few large-scale studies are available. We conducted a cohort study in which patients were identified in the Netherlands Cancer Registry in the Southeast of the Netherlands between 1990 and 2010. Of these patients, we collected all clinical characteristics and re-reviewed pathologic material to confirm NLPHL diagnosis. Seventy-three histologically confirmed cases of NLPHL were analyzed with a median follow-up of 65 months (range 4-257 months). Median age at diagnosis was 43 years (range 1-87); 84.9 % of the patients were male; B symptoms were present in 5.5 %; and stage I/II disease was most common (75.4 %). Patients were primarily treated with radiotherapy (50.7 %), chemotherapy (26 %), combined modality (radiotherapy and chemotherapy) (11 %), or surgical excision with careful watch-and-wait (12.3 %). Relapses occurred in seven patients (9.6 %) after a median of 26 months (21-74 months). Six patients (8.2 %) developed histologic transformation to large cell lymphoma. Five patients (6.8 %) died during follow-up due to progression of NLPHL (n = 1), histologic transformation (n = 2) and intercurrent deaths (n = 2). The estimated 10-year overall survival was 94.0 % and the 10-year progression-free survival 75.8 %. Our study confirms the distinct characteristics of NLPHL with a relatively good long-term prognosis. It may be possible to reduce treatment intensity in early stage NLPHL without affecting long-term outcome.

Cardiovascular risk outcome and program evaluation of a cluster randomised controlled trial of a community-based, lay peer led program for people with diabetes.

BACKGROUND: The 2013 Global Burden of Disease Study demonstrated the increasing burden of diabetes and the challenge it poses to the health systems of all countries. The chronic and complex nature of diabetes requires active self-management by patients in addition to clinical management in order to achieve optimal glycaemic control and appropriate use of available clinical services. This study is an evaluation of a "real world" peer support program aimed at improving the control and management of type 2 diabetes (T2DM) in Australia. METHODS: The trial used a randomised cluster design with a peer support intervention and routine care control arms and 12-month follow up. Participants in both arms received a standardised session of self-management education at baseline. The intervention program comprised monthly community-based group meetings over 12 months led by trained peer supporters and active encouragement to use primary health care and other community resources and supports related to diabetes. Clinical, behavioural and other measures were collected at baseline, 6 and 12 months. The primary outcome was the predicted 5 year cardiovascular disease risk using the United Kingdom Prospective Diabetes Study (UKPDS) Risk Equation at 12 months. Secondary outcomes included clinical measures, quality of life, measures of support, psychosocial functioning and lifestyle measures. RESULTS: Eleven of 12 planned groups were successfully implemented in the intervention arm. Both the usual care and the intervention arms demonstrated a small reduction in 5 year UKPDS risk and the mean values for biochemical and anthropometric outcomes were close to target at 12 months. There were some small positive changes in self-management behaviours. CONCLUSIONS: The positive changes in self-management behaviours among intervention participants were not sufficient to reduce cardiovascular risk, possibly because approximately half of the study participants already had quite well controlled T2DM at baseline. Future research needs to address how to enhance community based programs so that they reach and benefit those most in need of resources and supports to improve metabolic control and associated clinical outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000469213 . Registered 16 June 2009.

Journey to Becoming a Neonatal Nurse Practitioner: Making the Decision to Enter Graduate School.

BACKGROUND: Neonatal nurse practitioners (NNPs) play an important role in caring for premature and ill infants. Currently, there is a shortage of NNPs to fill open positions. Understanding how nurses decide to become NNPs will help practicing nurse practitioners, managers, and faculty encourage and support nurses in considering the NNP role as a career choice. PURPOSE: To describe how nurses decide to enter graduate school to become nurse practitioners. METHODS: A qualitative study using semistructured interviews to explore how 11 neonatal intensive care unit nurses decided to enter graduate school to become NNPs. RESULTS: Key elements of specialization, discovery, career decision, and readiness were identified. Conditions leading to choosing the NNP role include working in a neonatal intensive care unit and deciding to stay in the neonatal area, discovering the NNP role, deciding to become an NNP, and readiness to enter graduate school. Important aspects of readiness are developing professional self-confidence and managing home, work, and financial obligations and selecting the NNP program. IMPLICATIONS FOR PRACTICE: Neonatal nurse practitioners are both positive role models and mentors to nurses considering the role. Unit managers are obligated to provide nurses with opportunities to obtain leadership skills. Faculty of NNP programs must be aware of the impact NNP students and graduates have on choices of career and schools. IMPLICATIONS FOR RESEARCH: Exploring the decision to become an NNP in more geographically diverse populations will enhance understanding how neonatal intensive care unit nurses decide to become NNPs.

Wolff-Parkinson-White Syndrome in a Term Infant Presenting With Cardiopulmonary Arrest.

BACKGROUND: Wolff-Parkinson-White syndrome is a congenital abnormality of the cardiac conduction system caused by the presence of an abnormal accessory electrical pathway between the atria and the ventricles. This can result in intermittent tachyarrhythmias such as supraventricular tachycardia. In rare occasions, sudden death may occur from atrial fibrillation with rapid ventricular conduction. Supraventricular tachycardia typically has a sudden onset and offset, classified as a paroxysmal arrhythmia. Because of the variable occurrence, Wolff-Parkinson-White syndrome may go undiagnosed in the immediate newborn period. PURPOSE: To highlight arrhythmia as a possible cause of sudden decompensation in infants. CASE FINDINGS/RESULTS: The clinical presentation of this infant is complex and a number of potential diagnoses were considered. Preexcitation on electrocardiogram resulted in the diagnosis of Wolff-Parkinson-White syndrome. IMPLICATIONS FOR PRACTICE: Nurses caring for infants should be alert to tachycardia and irregularities of the heart rate, including those in the prenatal history, and should report them for evaluation. While all parents should be taught to watch for signs of illness, parents of infants with Wolff-Parkinson-White have additional learning needs, including recognizing early signs and symptoms of heart failure.

Cleft lift procedure for pilonidal disease: technique and perioperative management.

Pilonidal disease is a common condition affecting young patients. It is often disruptive to their lifestyle due to recurrent abscesses or chronic wound drainage. The most common surgical treatment, "cystectomy," removes useful tissue unnecessarily and does not address the etiology of the condition. Herein, we describe the etiology of pilonidal disease and our technique for definitive management of pilonidal disease using the cleft lift procedure. In this paper, we present our method of performing the cleft lift procedure for pilonidal disease including perioperative management and surgical technique. We have used the cleft lift procedure in nearly 200 patients with pilonidal disease, in both primary and salvage procedures settings. It has been equally successful in both settings with a high rate of success. It results in a closed wound with relatively minimal discomfort and straightforward wound care. We have described our current approach to recurrent and complex pilonidal disease using the cleft lift procedure. Once learned, the cleft lift procedure is a straightforward and highly successful solution to a chronic and challenging condition.

[Aspiration in a specialised weaning unit--an underestimated problem]. / Aspiration auf der Weaningstation--ein unterschätztes Problem.

This retrospective case series shows that 45 % of patients aspirated straight after removal of the tracheal cannula. The present case series includes 82 patients with long-term mechanical ventilation (LTMV) admitted to a specialised weaning unit. Aspiration was proven after patients sipped water coloured with patent blue V. Colour was detected with a bronchoscope after passing through the tracheostoma and directed toward the VC. The aspiration rate in this study is in good agreement with other reports in the literature.We could find no significant statistical differences concerning age (p = 0.97), gender (47 % vs. 49), number of bronchoscopies (p = 0.91) and comorbidities (p = 0.326) between patients with and without aspiration. The duration of the stay at the ward and the duration of ventilation as well as the parameter Hb at the time of admission (p = 0.566), CO2(p = 0.288/p = 0.716), HCO3 (p = 0.915/p = 0.612) and CRP (p = 0.402/p = 0.523) at the time of admission and discharge also showed no significant differences.The Kaplan Meier curves show a considerable divergence between patients with and without aspiration. However, the Log Rank Test (p = 0.348) and the univariate Cox Regression (HR 1.4, 95 % CI 0.689 - 2.849) were not significant. We believe that this can be attributed to the event rate, which was too low in our collective. This trend to a higher mortality of patients with aspiration might be due to weakness of the respiratory muscles when there is reduced coughing. Proof of aspiration in these patients is only one aspect of a multidimensional problem. Larger, prospective cohort studies are needed to show whether aspiration can serve as a prognostic marker.

Cysteine protease activity of feline Tritrichomonas foetus promotes adhesion-dependent cytotoxicity to intestinal epithelial cells.

Trichomonads are obligate protozoan parasites most renowned as venereal pathogens of the reproductive tract of humans and cattle. Recently, a trichomonad highly similar to bovine venereal Tritrichomonas foetus but having a unique tropism for the intestinal tract was recognized as a significant cause of colitis in domestic cats. Despite a high prevalence, worldwide distribution, and lack of consistently effective drugs for treatment of the infection, the cellular mechanisms of T. foetus pathogenicity in the intestinal tract have not been examined. The aims of this study were to determine the pathogenic effect of feline T. foetus on porcine intestinal epithelial cells, the dependence of T. foetus pathogenicity on adhesion of T. foetus to the intestinal epithelium, and the identity of mediators responsible for these effects. Using an in vitro coculture approach to model feline T. foetus infection of the intestinal epithelium, these studies demonstrate that T. foetus promotes a direct contact-dependent activation of intestinal epithelial cell apoptosis signaling and progressive monolayer destruction. Moreover, these pathological effects were demonstrated to be largely dependent on T. foetus cell-associated cysteine protease activity. Finally, T. foetus cysteine proteases were identified as enabling cytopathic effects by promoting adhesion of T. foetus to the intestinal epithelium. The present studies are the first to examine the cellular mechanisms of pathogenicity of T. foetus toward the intestinal epithelium and support further investigation of the cysteine proteases as virulence factors in vivo and as potential therapeutic targets for ameliorating the pathological effects of intestinal trichomonosis.

Guidance for the gastrointestinal evaluation and management of iron deficiency in Sub-Saharan Africa.

BACKGROUND: Over 30% of the world's population is anaemic, with a significant proportion of these being iron deficient. As iron deficiency (ID) anaemia in men and post-menopausal women is mostly caused by gastrointestinal blood loss or malabsorption, the initial evaluation of a patient with ID anaemia involves referral to a gastroenterologist. The current drive towards patient blood management in sub-Saharan Africa (SSA)prescribes that we regulate not only the use of blood transfusion but also the management of patients in whom the cause of iron loss or inadequate iron absorption is sought. Recommendations have been developed to: (i) aid clinicians in the evaluation of suspected gastrointestinal iron loss and iron malabsorption, and often a combination of these; (ii) improve clinical outcomes for patients with gastrointestinal causes of ID; (iii) provide current, evidence-based, context-specific recommendations for use in the management of ID; and (iv) conserve resources by ensuring rational utilisation of blood and blood products. METHOD: Development of the guidance document was facilitated by the Gastroenterology Foundation of Sub-Saharan Africa and the South African Gastroenterology Society. The consensus recommendations are based on a rigorous process involving 21 experts in gastroenterology and haematology in SSA. Following discussion of the scope and purpose of the guidance document among the experts, an initial review of the literature and existing guidelines was undertaken. Thereafter, draft recommendation statements were produced to fulfil the outlined purpose of the guidance document. These were reviewed in a round-table discussion and were subjected to two rounds of anonymised consensus voting by the full committee in an electronic Delphi exercise during 2022 using the online platform, Research Electronic Data Capture. Recommendations were modified by considering feedback from the previous round, and those reaching a consensus of over 80% were incorporated into the final document. Finally, 44 statements in the document were read and approved by all members of the working group. CONCLUSION: The recommendations incorporate six areas, namely: general recommendations and practice, Helicobacter pylori, coeliac disease, suspected small bowel bleeding, inflammatory bowel disease, and preoperative care. Implementation of the recommendations is aimed at various levels from individual practitioners to healthcare institutions, departments and regional, district, provincial and national platforms. It is intended that the recommendations spur the development of centre-specific guidelines and that they are integrated with the relevant patient blood management protocols. Integration of the recommendations is intended to promote optimal evaluation and management of patients with ID, regardless of the presence of anaemia.

Pulsed processing by cold plasma, applied to industrial emission control.

A promising pollution control technology is cold plasma driven chemical processing. The plasma is a pulsed electric gas discharge inside a near atmospheric-pressure-temperature reactor. The system is energized by a continuous stream of very short high-voltage pulses. The exhaust gas to be treated flows through the reactor. The methods applied involve the development of robust cold plasma systems, industrial applications and measuring technologies. Tests of the systems were performed at many industrial sites and involved control of airborne VOC (volatile organic compound) and odor. Electrical, chemical and odor measuring data were collected with state-of-the-art methods. To explain the test data an approximate solution of global reaction kinetics of pulsed plasma chemistry was developed. It involves the Lambert function and, for convenience, a simple approximation of it. The latter shows that the amount of removal, in good approximation, is a function of a single variable. This variable is electric plasma power divided by gas flow divided by input concentration. In the results sections we show that in some cases up to 99% of volatile pollution can be removed at an acceptable energy requirement. In the final sections we look into future efficiency enhancements by implementation of (sub)nanosecond pulsed plasma and solid state high-voltage technology and by integration with catalyst technology.

The role of mitochondrial function and cellular bioenergetics in ageing and disease.

Mitochondria constitute an important topic of biomedical enquiry (one paper in every 154 indexed in PubMed since 1998 is retrieved by the keyword 'mitochondria') because of widespread recognition of their importance in cell physiology and pathology. Mitochondrial dysfunction is widely implicated in ageing and in the diseases of ageing, through dysfunction in adenosine triphosphate (ATP) synthesis, Ca(2+) homeostasis, central metabolic pathways or radical production. Nonetheless, the mechanisms and regulation of superoxide and hydrogen peroxide formation by mitochondria remain poorly described. Measurement of the capacities of different sites of superoxide and hydrogen peroxide production in isolated skeletal muscle mitochondria show that the maximum capacities of sites in complexes I, II and III and in several associated redox enzymes greatly exceed the native rates observed in the absence of respiratory chain inhibitors. In vitro, the native rates and the relative importance of different sites both depend on the substrate being oxidized, with sites IQ, IIF, GPDH, IF and IIIQo each being important with particular substrates. The techniques involved in measuring rates from each site should become applicable to cell cultures and in vivo in the future.

A mismatch between aortic pulse pressure and pulse wave velocity predicts advanced peripheral arterial disease.

OBJECTIVES: To determine whether increases in central aortic pulse pressure (PPc), but decreases in carotid-femoral pulse wave velocity (PWV) predict the presence of advanced peripheral arterial disease (PAD). METHODS: Applanation tonometry and vascular ultrasound were employed to assess carotid-femoral PWV, PPc, and carotid intima media thickness (IMT) in 136 patients of African ancestry with chronic critical lower limb ischaemia (CLI) and in 1,030 randomly selected healthy adults of African ancestry, 194 of whom were age- and sex matched (controls). RESULTS: With adjustments for confounders, compared with age- and sex-matched controls, participants with CLI had an increased carotid IMT (p = .0001) and PPc (p < .0001), but a markedly reduced PWV (m/second) (CLI = 5.7 ± 3.7, controls = 8.6 ± 3.4, p < .0001). PWV was correlated with PPc in controls (r = .52, p < .0001), but not in CLI (r = -.06). A PPc/PWV mismatch index showed increased values in participants with CLI over the full adult age range assessed. With carotid IMT, PPc, or aortic augmentation index in the same regression model, an increase in the PPc/PWV mismatch index was independently associated with CLI (p < .0001) and a PPc/PWV value upper 95% confidence interval in the community sample predicted CLI (odds ratio = 32 [6-169], p < .0001). PPc/PWV predicted CLI with a similar level of performance and accuracy and a greater specificity (98%) than that of IMT (82%). CONCLUSION: In CLI, while PPc increases, carotid-femoral PWV is markedly reduced. A PPc/PWV mismatch may be a new risk marker for advanced PAD.