Etiology and Clinical Evaluation of Patients with Bronchiectasis in a Tertiary Hospital in Nigeria.

BACKGROUND: Bronchiectasis is often considered an orphan disease in developed societies. This may not be the case with low-income countries. Currently there is a paucity of data on the pattern and presentation of this condition in Nigeria. OBJECTIVE: This study was undertaken to determine the frequency and pattern of presentation of bronchiectasis in a tertiary healthcare facility in Uyo, South-South, Nigeria. METHODS: We carried out a three-year prospective study of adult patients aged between 15-85 years diagnosed with bronchiectasis in the University of Uyo Teaching Hospital in Uyo, Nigeria between 2016 and 2019. RESULTS: Eighty-two patients were identified from the clinic register. Out of these, 76 were recruited into the study; made up of 44(57.9%) males and 32 (42.1%) females. The average age of the patients was 49.7 ± 14.1 years. Sixteen (21.1%) of the patients were HIV positive. Forty-four (57.9%) patients had previously been treated for pulmonary tuberculosis. Majority of the patients; 72 (94.7%) had chronic productive cough. Sixty-four (84.2%) had at least one episode of exacerbation within the last 12 months while 36(47.4%) had a severe exacerbation requiring hospitalisation. Hospitalisation was associated with several factors with the strongest contributor being the presence of respiratory distress on physical examination (OR 15.4 p= 0.002). CONCLUSION: Bronchiectasis is not an uncommon disease amongst our patients. A previous history of pulmonary tuberculosis is the commonest associated predisposing medical condition. There is a high rate of exacerbation among these patients with respiratory distress as the strongest predictor of hospitalisation.

CONTEXTE: La bronchectasie est souvent considérée comme une maladie orpheline dans les sociétés développées.Ce n'est peut-être pas le cas dans pays à faible revenu. Actuellement, il y a une pénurie de données sur les caractéristiques et la présentation de cette maladie au Nigeria. OBJECTIF: Cette étude a été entreprise pour déterminer la fréquence et le mode de présentation de la bronchectasie dans un établissement de soins tertiaires à Uyo, dans le sud-sud du Nigeria. MÉTHODES: Nous avons mené une étude prospective sur trois ans auprès de patients adultes âgés de 15 à 85 ans chez qui on a diagnostiqué une bronchectasie dans l'hôpital universitaire d'Uyo, à Uyo, entre 2016 et 2019. Uyo, au Nigeria, entre 2016 et 2019. RÉSULTATS: Quatre-vingt-deux patients ont été identifiés à partir du registre de la clinique registre. Parmi ceux-ci, 76 ont été recrutés dans l'étude ; composés de 44 (57,9 %) hommes et 32 (42,1 %) femmes. L'âge moyen des patients était de 49,7 ± 14,1 ans. Seize (21,1 %) des patients étaient séropositifs. Quarante-quatre (57,9 %) patients avaient déjà été traités pour une tuberculose pulmonaire.La majorité des patients ; 72 (94,7%) avaient une toux productive chronique. Soixante-quatre (84,2 %) ont eu au moins un épisode d'exacerbation au cours des 12 derniers mois, tandis que 36 (47,4 %) ont eu une exacerbation sévère nécessitant une hospitalisation. L'hospitalisation était associée à plusieurs facteurs, le facteur le plus important étant la présence d'une présence d'une détresse respiratoire à l'examen physique (OR 15.4 p= 0.002). CONCLUSION: La bronchectasie n'est pas une maladie rare parmi nos patients. Un antécédent de tuberculose pulmonaire est l'état médical prédisposant le plus fréquent.ll existe un taux élevé d'exacerbation chez ces patients, la détresse respiratoire étant le facteur prédictif le plus fort d'hospitalisation. MOTS CLÉS: Étiologie, Caractéristiques cliniques, Bronchiectasie, Exacerbation, Hospitalisation.

Challenges of Case Management of COVID-19 in University of Uyo Teaching Hospital: A One-Year Experience.

BACKGROUND AND OBJECTIVES: Coronavirus disease 2019 (COVID-19) is a global pandemic. Older people and those with poorly controlled co-morbidities have higher risk of mortality. This study was conducted to highlight the clinical features, challenges of management and outcome for the patients we have seen in our centre over the past one year. METHODS: This was a retrospective cross-sectional study involving all patients admitted in the COVID-19 Isolation unit of University of Uyo Teaching Hospital (UUTH) from June, 2020-May, 2021. Clinical and laboratory information were obtained from the patient case notes. Ethical clearance for the conduct of the study was obtained from the Ethics committee, UUTH, Uyo. Data was analysed with STATA version 13. RESULTS: Thirty-three (37.9%) patients were COVID-19 PCR positive. The mean ± SD age of COVID-19 PCR positive patients was 57.3 ± 13.4 years with majority (69.7%) being above 50 years. There was a male preponderance (75%). Eleven (34.4%) patients died while 21(65.6%) were discharged. The highest co-morbidity associated with COVID-19 mortality was diabetes mellitus (7 out of 11; 63.6%). There was a poor uptake of supportive investigations for the management of COVID-19 patients. A raised body temperature (P=0.0006), a low SPO2 (0.00004), high respiratory rate (0.0009) on admission and shorter duration of admission (0.0002), were associated with mortality. CONCLUSION: The presence of co-morbidities, fever, low SPO2 and high respiratory rates on admission are associated with increased mortality from COVID-19 disease. A paucity of supportive investigations was a major challenge to COVID-19 management. We therefore recommend the strengthening of our laboratory capacity.

CONTEXTE ET OBJECTIFS: La maladie de coronavirus 2019 (COVID-19) est une pandémie mondiale. Les personnes âgées et celles qui présentent des comorbidités mal contrôlées ont un risque de mortalité plus élevé. Cette étude a été menée pour mettre en évidence les caractéristiques cliniques, les défis de la gestion et le résultat des patients que nous avons vus dans notre centre au cours de la dernière année. MÉTHODES: Il s'agissait d'une étude transversale rétrospective impliquant tous les patients admis dans l'unité d'isolement COVID- 19 de l'University of Uyo Teaching Hospital (UUTH) de juin 2020 à mai 2021. Les informations cliniques et de laboratoire ont été obtenues à partir des notes de cas des patients. L'autorisation éthique pour la réalisation de l'étude a été obtenue auprès du comité d'éthique de l'UUTH, Uyo. Les données ont été analysées avec STATA version 13. RÉSULTATS: Trente-trois (37,9%) patients étaient positifs à la PCR COVID-19. L'âge moyen ± SD des patients positifs au COVID-19 PCR était de 57,3 ± 13,4 ans, la majorité (69,7%) ayant plus de 50 ans. Il y avait une prépondérance masculine (75 %). Onze (34,4 %) patients sont décédés et 21 (65,6 %) sont sortis de l'hôpital. La comorbidité la plus importante associée à la mortalité de COVID-19 était le diabète miletus (7 sur 11 : 63 : 6 %). Les investigations de soutien pour la gestion des patients COVID-19 ont été peu utilisées. Une température corporelle élevée (P=0,0006), une faible SPO2 (0,00004), une fréquence respiratoire élevée (0,0009) à l'admission et une durée d'admission plus courte (0,0002) étaient associées à la mortalité. CONCLUSION: La présence de comorbidités, de fièvre, d'une faible SPO2 et d'une fréquence respiratoire élevée à l'admission est associée à une mortalité accrue de la maladie de COVID-19. Le manque d'investigations de soutien a été un défi majeur pour la gestion de la maladie COVID-19. Nous recommandons donc le renforcement de la capacité de nos laboratoires. Mots clés: COVID-19, défis, gestion des cas, Nigeria.

[German S1 Guideline Long-/Post-COVID]. / S1-Leitlinie Long-/Post-COVID.

The German Society of Pneumology initiated 2021 the AWMF S1 guideline Long COVID/Post-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendations describe current Long COVID/Post-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an explicit practical claim and will be developed and adapted by the author team based on the current increase in knowledge.

Psychological distress and health-related quality of life among stable patients with bronchiectasis.

BACKGROUND: Bronchiectasis is characterized by chronic symptoms and impaired physical activity. Anxiety and depression usually complicate chronic illness. Thus, underdiagnosis of psychological distress in bronchiectasis may lead to increased morbidity and mortality. AIMS: The aim of this study is to evaluate the impact of physical illness on psychological distress and its association with health-related quality of life (HRQOL). SUBJECTS AND METHODS: This is a cross-sectional study of adults with bronchiectasis. Patients completed a study questionnaire, the hospital anxiety and depression scale and the World Health Organization quality of life brief (WHOQOL-BREF) questionnaire. Physical examination was conducted on all participants. RESULTS: 103 patients were recruited for this study: 54 males (52.4%) and 49 females (47.6%). The average age of the patients was 49.12 ± 14.37 years. The most common predisposing factor for bronchiectasis amongst the patients was previous pulmonary tuberculosis (51 patients, 49.5%). Chronic productive cough, which was reported by 98 of the subjects (95.15%), was the most common symptom. 89 subjects (86.41%) reported episodes of shortness of breath, 82 (79.61%) reported at least one episode of exacerbation, while 52 subjects (50.49%) were hospitalized for bronchiectasis in the previous 12 months. 23 subjects (22.3%) had anxiety and 32 (31.1%) had depression. Anxiety and depression were significantly associated with indicators of severe disease. The subjects recorded low HRQOL scores across all domains. Psychological distress displayed a significant negative association with all the quality-of-life domains except between anxiety and social interaction. CONCLUSION: Symptoms of depression and anxiety are common among patients with bronchiectasis and these symptoms have a negative impact on HRQOL.

Identification of IgG1 isotype phosphorylcholine antibodies for the treatment of inflammatory cardiovascular diseases.

BACKGROUND: Phosphorylcholine (PC) is an important pro-inflammatory damage-associated molecular pattern. Previous data have shown that natural IgM anti-PC protects against cardiovascular disease. We aimed to develop a monoclonal PC IgG antibody with anti-inflammatory and anti-atherosclerotic properties. METHODS: Using various techniques PC antibodies were validated and optimized. In vivo testing was performed in a femoral artery cuff model in ApoE3*Leiden mice. Safety studies are performed in rats and cynomolgus monkeys. RESULTS: A chimeric anti-PC (PC-mAb(T15), consisting of a human IgG1 Fc and a mouse T15/E06 Fab) was produced, and this was shown to bind specifically to epitopes in human atherosclerotic tissues. The cuff model results in rapid induction of inflammatory genes and altered expression of genes associated with ER stress and choline metabolism in the lesions. Treatment with PC-mAb(T15) reduced accelerated atherosclerosis via reduced expression of endoplasmic reticulum stress markers and CCL2 production. Recombinant anti-PC Fab fragments were identified by phage display and cloned into fully human IgG1 backbones creating a human monoclonal IgG1 anti-PC (PC-mAbs) that specifically bind PC, apoptotic cells and oxLDL. Based on preventing macrophage oxLDL uptake and CCL2 production, four monoclonal PC-mAbs were selected, which to various extent reduced vascular inflammation and lesion development. Additional optimization and validation of two PC-mAb antibodies resulted in selection of PC-mAb X19-A05, which inhibited accelerated atherosclerosis. Clinical grade production of this antibody (ATH3G10) significantly attenuated vascular inflammation and accelerated atherosclerosis and was tolerated in safety studies in rats and cynomolgus monkeys. CONCLUSIONS: Chimeric anti-PCs can prevent accelerated atherosclerosis by inhibiting vascular inflammation directly and through reduced macrophage oxLDL uptake resulting in decreased lesions. PC-mAb represents a novel strategy for cardiovascular disease prevention.

Increased case-finding and uptake of direct-acting antiviral treatment essential for micro-elimination of hepatitis C among people living with HIV: a national record linkage study.

OBJECTIVES: Micro-elimination of hepatitis C virus (HCV) in people living with HIV (PLHIV) and co-infected with HCV has been proposed as a key contribution to the overall goal of HCV elimination. While other studies have examined micro-elimination in HIV-treated cohorts, few have considered HCV micro-elimination among those not treated for HIV or at a national level. METHODS: Through data linkage of national and sentinel surveillance data, we examined the extent of HCV testing, diagnosis and treatment among a cohort of PLHIV in Scotland identified through the national database of HIV-diagnosed individuals, up to the end of 2017. RESULTS: Of 5018 PLHIV, an estimated 797 (15%) had never been tested for HCV and 70 (9%) of these had undiagnosed chronic HCV. The odds of never having been tested for HCV were the highest in those not on HIV treatment [adjusted odds ratio (aOR) = 7.21, 95% confidence interval (CI): 5.15-10.10). Overall HCV antibody positivity was 11%, and it was at its highest among people who inject drugs (49%). Most of those with chronic HCV (91%) had attended an HCV treatment clinic but only half had been successfully treated (54% for those on HIV treatment, 12% for those not) by the end of 2017. The odds of never having been treated for HCV were the highest in those not on HIV treatment (aOR = 3.60, 95% CI: 1.59-8.15). CONCLUSIONS: Our data demonstrate that micro-elimination of HCV in PLHIV is achievable but progress will require increased effort to engage and treat those co-infected, including those not being treated for their HIV.

Adult skin acute stress responses to short-term environmental and internal aggression from exposome factors.

Exposome factors that lead to stressed skin can be defined as any disturbance to homeostasis from environmental (meteorological factors, solar radiation, pollution or tobacco smoke) and/or internal exposure (unhealthy diet, hormonal variations, lack of sleep, psychosocial stress). The clinical and biological impact of chronic exposome effects on skin functions has been extensively reviewed, whereas there is a paucity of information on the impact of short-term acute exposure. Acute stress, which would typically last minutes to hours (and generally no more than a week), provokes a transient but robust neuroendocrine-immune and tissue remodelling response in the skin and can alter the skin barrier. Firstly, we provide an overview of the biological effects of various acute stressors on six key skin functions, namely the skin physical barrier, pigmentation, defences (antioxidant, immune cell-mediated, microbial and microbiome maintenance), structure (extracellular matrix and appendages), neuroendocrine and thermoregulation functions. Secondly, we describe the biological and clinical effects on adult skin from individual exposome factors that elicit an acute stress response and their consequences in skin health maintenance. Clinical manifestations of acutely stressed skin may include dry skin that might accentuate fine lines, oily skin, sensitive skin, pruritus, erythema, pale skin, sweating, oedema and flares of inflammatory skin conditions such as acne, rosacea, atopic dermatitis, pigmentation disorders and skin superinfection such as viral reactivation. Acute stresses can also induce scalp sensitivity, telogen effluvium and worsen alopecia.

Monofunctionalized Gold Nanoparticles: Fabrication and Applications.

An overview of various approaches to synthesize gold nanoparticles (AuNPs) bearing one single chemically addressable unit and their diverse fields of application is presented. This comprehensive review not only describes the strategies pursued to obtain monofunctionalized AuNPs, but also reports their behavior as 'massive' molecules in wet chemical protocols and the scope of their applications. The latter reaches from site-specific labels in biomolecules over mechanical barriers in superstructures to building blocks in hybrid nano-architectures. The complementing physical properties of AuNPs combined with precise chemical control of their attachment makes these objects promising building blocks for numerous proof-of-concept experiments and applications.

ΔK=0 M1 Excitation Strength of the Well-Deformed Nucleus

The size of a ΔK=0 M1 excitation strength has been determined for the first time in a predominantly axially deformed even-even nucleus. It has been obtained from the observation of a rare K-mixing situation between two close-lying J^{π}=1^{+} states of the nucleus ^{164}Dy with components characterized by intrinsic projection quantum numbers K=0 and K=1. Nuclear resonance fluorescence induced by quasimonochromatic linearly polarized γ-ray beams provided evidence for K mixing of the 1^{+} states at 3159.1(3) and 3173.6(3) keV in excitation energy from their γ-decay branching ratios into the ground-state band. The ΔK=0 transition strength of B(M1;0_{1}^{+}→1_{K=0}^{+})=0.008(1)µ_{N}^{2} was inferred from a mixing analysis of their M1 transition rates into the ground-state band. It is in agreement with predictions from the quasiparticle phonon nuclear model. This determination represents first experimental information on the M1 excitation strength of a nuclear quantum state with a negative R-symmetry quantum number.

Absence of Low-Energy Shape Coexistence in

The ^{80}Ge structure was investigated in a high-statistics ß-decay experiment of ^{80}Ga using the GRIFFIN spectrometer at TRIUMF-ISAC through γ, ß-e, e-γ, and γ-γ spectroscopy. No evidence was found for the recently reported 0_{2}^{+} 639-keV level suggested as evidence for low-energy shape coexistence in ^{80}Ge. Large-scale shell model calculations performed in ^{78,80,82}Ge place the 0_{2}^{+} level in ^{80}Ge at 2 MeV. The new experimental evidence combined with shell model predictions indicate that low-energy shape coexistence is not present in ^{80}Ge.

Effect of microchannel structure and fluid properties on non-inertial particle migration.

In this work, we investigate the influence of channel structure and fluid rheology on non-inertial migration of non-Brownian polystyrene beads. Particle migration in this regime can be found in biomedical, chemical, environmental and geological applications. However, the effect of fluid rheology on particle migration in porous media remains to be clearly understood. Here, we isolate the effects of elasticity and shear thinning by comparing a Newtonian fluid, a purely elastic (Boger) fluid, and a shear-thinning elastic fluid. To mimic the complexity of geometries in real-world application, a random porous structure is created through a disordered arrangement of cylindrical pillars in the microchannel. Experiments are repeated in an empty channel and in channels with an ordered arrangement of pillars, and the similarities and differences in the observed particle focusing are analyzed. It is found that elasticity drives the particles away from the channel walls in an empty microchannel. Notably, particle focusing is unaffected by curved streamlines in an ordered porous microchannel and particles stay away from pillars in elastic fluids. Shear-thinning is found to reduce the effect of focusing and a broader region of particle concentration is observed. It is also noteworthy that the rheological characteristics of the fluid are not important for the particle distribution in a randomly arranged pillared microchannel and particles have a uniform distribution for all suspending fluids. Moreover, discussion on the current discrepancy in the literature about the equilibrium positions of the particles in a channel is extended by analyzing the results obtained in the current experiments.

A qualitative study of the acceptability of cognitive bias modification for paranoia (CBM-pa) in patients with psychosis.

BACKGROUND: Cognitive Bias Modification (CBM) has been used successfully as a computer-based intervention in disorders such as anxiety. However, CBM to modify interpretations of ambiguous information relevant to paranoia has not yet been tested. We conducted a qualitative investigation of a novel intervention called CBM for paranoia (CBM-pa) to examine its acceptability in patients with psychosis. METHODS: Eight participants with psychosis who completed CBM-pa were identified by purposive sampling and invited for a semi-structured interview to explore the facilitators and barriers to participation, optimum form of delivery, perceived usefulness of CBM-pa and their opinions on applying CBM-pa as a computerised intervention. The interviews were transcribed and analysed using thematic analysis by researchers working in collaboration with service users. RESULTS: Themes emerged relating to participants' perception about delivery, engagement, programme understanding, factors influencing experience, perceived impact and application of CBM-pa. CBM-pa was regarded as easy, straightforward and enjoyable. It was well-accepted among those we interviewed, who understood the procedure as a psychological intervention. Patients reported that it increased their capacity for adopting alternative interpretations of emotionally ambiguous scenarios. Although participants all agreed on the test-like nature of the current CBM-pa format, they considered that taking part in sessions had improved their overall wellbeing. Most of them valued the computer-based interface of CBM-pa but favoured the idea of combining CBM-pa with some form of human interaction. CONCLUSIONS: CBM-pa is an acceptable intervention that was well-received by our sample of patients with paranoia. The current findings reflect positively on the acceptability and experience of CBM-pa in the target population. Patient opinion supports further development and testing of CBM-pa as a possible adjunct treatment for paranoia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN: 90749868 . Retrospectively registered on 12 May 2016.

The digestive system of the stony coral Stylophora pistillata.

Because hermatypic species use symbiotic algal photosynthesis, most of the literature in this field focuses on this autotrophic mode and very little research has studied the morphology of the coral's digestive system or the digestion process of particulate food. Using histology and histochemestry, our research reveals that Stylophora pistillata's digestive system is concentrated at the corals' peristome, actinopharynx and mesenterial filaments (MF). We used in-situ hybridization (ISH) of the RNA transcript of the gene that codes for the S. pistillata digestive enzyme, chymotrypsinogen, to shed light on the functionality of the digestive system. Both the histochemistry and the ISH pointed to the MF being specialized digestive organs, equipped with large numbers of acidophilic and basophilic granular gland cells, as well as acidophilic non-granular gland cells, some of which produce chymotrypsinogen. We identified two types of MF: short, trilobed MF and unilobed, long and convoluted MF. Each S. pistillata polyp harbors two long convoluted MF and 10 short MF. While the short MF have neither secreting nor stinging cells, each of the convoluted MF display gradual cytological changes along their longitudinal axis, alternating between stinging and secreting cells and three distinctive types of secretory cells. These observations indicate the important digestive role of the long convoluted MF. They also indicate the existence of novel feeding compartments in the gastric cavity of the polyp, primarily in the nutritionally active peristome, in the actinopharynx and in three regions of the MF that differ from each other in their cellular components, general morphology and chymotrypsinogen excretion.

Viscoelastic flow past mono- and bidisperse random arrays of cylinders: flow resistance, topology and normal stress distribution.

We investigate creeping viscoelastic fluid flow through two-dimensional porous media consisting of random arrangements of monodisperse and bidisperse cylinders, using our finite volume-immersed boundary method introduced in S. De, et al., J. Non-Newtonian Fluid Mech., 2016, 232, 67-76. The viscoelastic fluid is modeled with a FENE-P model. The simulations show an increased flow resistance with increase in flow rate, even though the bulk response of the fluid to shear flow is shear thinning. We show that if the square root of the permeability is chosen as the characteristic length scale in the determination of the dimensionless Deborah number (De), then all flow resistance curves collapse to a single master curve, irrespective of the pore geometry. Our study reveals how viscoelastic stresses and flow topologies (rotation, shear and extension) are distributed through the porous media, and how they evolve with increasing De. We correlate the local viscoelastic first normal stress differences with the local flow topology and show that the largest normal stress differences are located in shear flow dominated regions and not in extensional flow dominated regions at higher viscoelasticity. The study shows that normal stress differences in shear flow regions may play a crucial role in the increase of flow resistance for viscoelastic flow through such porous media.

Relation between postoperative ileus and anastomotic leakage after colorectal resection: a post hoc analysis of a prospective randomized controlled trial.

AIM: Anastomotic leakage (AL) following abdominal surgery is a critical determinant of postoperative recovery, of which the aetiology is largely unknown. Interestingly, interventions aimed at reducing the inflammatory response and postoperative ileus (POI) have an unexpected effect on AL. The aim of this study was to investigate the relation of POI with inflammation and AL after colorectal resection. METHOD: A post hoc analysis of a prospective randomized controlled trial in which patients underwent a colorectal resection was performed. Patients undergoing a colorectal resection were stratified into having or not having POI. The incidence of AL and other clinical parameters was registered prospectively. Intestinal fatty acid binding protein (I-FABP, a marker for tissue damage) and the inflammatory response in plasma and colon tissue were determined. RESULTS: AL was present in nine of 43 patients in the POI group, and in one of 65 in the group without POI (P < 0.001). There was a significant association between POI and AL (OR 12.57, 95% CI: 2.73-120.65; P = 0.0005). Patients with POI had significantly higher plasma levels of soluble tumour necrosis factor receptor 1 (TNFRSF1A) at 4 h postoperatively (0.89 ng/l, interquartile range 0.56) than patients without POI (0.80 ng/l, interquartile range 0.37; P = 0.04) and higher plasma levels of C-reactive protein on the second day postoperatively (234 ± 77 vs 163 ± 86 mg/l; P = 0.001). Patients who developed AL had significantly higher plasma levels of I-FABP compared with patients without AL at 24 h after onset of surgery. CONCLUSION: POI is associated with a higher prevalence of AL and an increased inflammatory response.

Regulation of myoglobin in hypertrophied rat cardiomyocytes in experimental pulmonary hypertension.

A major problem in chronic heart failure is the inability of hypertrophied cardiomyocytes to maintain the required power output. A Hill-type oxygen diffusion model predicts that oxygen supply is limiting in hypertrophied cardiomyocytes at maximal rates of oxygen consumption and that this limitation can be reduced by increasing the myoglobin (Mb) concentration. We explored how cardiac hypertrophy, oxidative capacity, and Mb expression in right ventricular cardiomyocytes are regulated at the transcriptional and translational levels in an early stage of experimental pulmonary hypertension, in order to identify targets to improve the oxygen supply/demand ratio. Male Wistar rats were injected with monocrotaline to induce pulmonary hypertension (PH) and right ventricular heart failure. The messenger RNA (mRNA) expression levels per nucleus of growth factors insulin-like growth factor-1Ea (IGF-1Ea) and mechano growth factor (MGF) were higher in PH than in healthy controls, consistent with a doubling in cardiomyocyte cross-sectional area (CSA). Succinate dehydrogenase (SDH) activity was unaltered, indicating that oxidative capacity per cell increased. Although the Mb protein concentration was unchanged, Mb mRNA concentration was reduced. However, total RNA per nucleus was about threefold higher in PH rats versus controls, and Mb mRNA content expressed per nucleus was similar in the two groups. The increase in oxidative capacity without an increase in oxygen supply via Mb-facilitated diffusion caused a doubling of the critical extracellular oxygen tension required to prevent hypoxia (PO2crit). We conclude that Mb mRNA expression is not increased during pressure overload-induced right ventricular hypertrophy and that the increase in myoglobin content per myocyte is likely due to increased translation. We conclude that increasing Mb mRNA expression may be beneficial in the treatment of experimental PH.

Interventions in the management of infection in the foot in diabetes: a systematic review.

The expert panel on diabetic foot infection (DFI) of the International Working Group on the Diabetic Foot conducted a systematic review seeking all published reports relating to any type of treatment for infection of the foot in persons with diabetes published as of 30 June 2014. This review, conducted with both PubMed and EMBASE, was used to update an earlier one undertaken on 30 June 2010 using the same search string. Eligible publications included those that had outcome measures reported for both a treated and a control population that were managed either at the same time, or as part of a before-and-after case design. We did not include studies that contained only information related to definition or diagnosis, but not treatment, of DFI. The current search identified just seven new articles meeting our criteria that were published since the 33 identified with the previous search, making a total of 40 articles from the world literature. The identified articles included 37 randomised controlled trials (RCTs) and three cohort studies with concurrent controls, and included studies on the use of surgical procedures, topical antiseptics, negative pressure wound therapy and hyperbaric oxygen. Among the studies were 15 RCTs that compared outcomes of treatment with new antibiotic preparations compared with a conventional therapy in the management of skin and soft tissue infection. In addition, 10 RCTs and 1 cohort study compared different treatments for osteomyelitis in the diabetic foot. Results of comparisons of different antibiotic regimens generally demonstrated that newly introduced antibiotic regimens appeared to be as effective as conventional therapy (and also more cost-effective in one study), but one study failed to demonstrate non-inferiority of a new antibiotic compared with that of a standard agent. Overall, the available literature was both limited in both the number of studies and the quality of their design. Thus, our systematic review revealed little evidence upon which to make recommendations for treatment of DFIs. There is a great need for further well-designed trials that will provide robust data upon which to make decisions about the most appropriate treatment of both skin and soft tissue infection and osteomyelitis in diabetic patients.

Appraisals of psychotic experiences: an experimental investigation of symptomatic, remitted and non-need-for-care individuals.

BACKGROUND: Appraisals are suggested to play a determining role in the clinical outcome of psychotic experiences (PEs). We used experimental tasks that mimic PEs to investigate appraisals in individuals with PEs with and without a 'need-for-clinical-care', and psychosis patients whose symptoms have remitted. We predicted that patients would appraise the tasks as threatening regardless of current symptom level, while non-clinical and control groups would appraise them as non-threatening. METHOD: Appraisals following three anomalous experiences-inducing tasks [Telepath, Cards task, Virtual acoustic space paradigm (VASP)] were examined in 71 individuals: symptomatic (n = 18) and remitted (n = 16) psychosis patients; non-clinical group with PEs (n = 16); controls without PEs (n = 21). RESULTS: As predicted, symptomatic patients endorsed more threatening appraisals for all tasks than non-clinical and control groups, who did not differ from each other. However, remitted patients were less likely to endorse threatening appraisals of the Cards and Telepath than their symptomatic counterparts, although they did not differ in global ratings of how striking, threatening and distressing they found the tasks. Moreover, remitted participants endorsed more threatening appraisals of the Telepath and VASP than non-clinical participants, and of the VASP than controls. Remitted participants also rated all three tasks as globally more threatening than the non-clinical group and controls. CONCLUSIONS: Clinical outcome may not necessarily be driven by the presence of symptoms, with threatening appraisals of PEs representing a key factor. The remitted group's intermediate appraisal scores imply that the relationship between appraisal and clinical outcome is not straightforward, and potential mediating factors need to be determined.

The microbiome of diabetic foot osteomyelitis.

The purpose of this investigation was to evaluate the diversity of bacteria in diabetic foot osteomyelitis using a 16S rRNA sequencing approach and to compare the results with conventional culture techniques. In this prospective observational study, we obtained 34 bone samples from patients admitted to our hospital with a moderate-severe diabetic foot infection. We analysed the distribution of the 16S rRNA gene sequences in the bone samples, using an Illumina MiSeq Personal Sequencer. We compared the genera that were detected with the cultured pathogens in the bone samples with conventional techniques. In the 23 samples that had positive results with both techniques, Staphylococcus, Corynebacterium, Streptococcus and Propionibacterium spp. were detected in 20, 18, 13 and 11 samples, respectively. Significantly more anaerobes were detected with 16S rRNA sequencing compared to conventional techniques (86.9 % vs. 23.1 %, p = 0.001) and more Gram-positive bacilli were present (78.3 % vs. 3.8 %, p < 0.001). Staphylococcus spp. were identified in all of the sequenced bone samples that were negative with conventional techniques. Mixed genera were present in 83.3 % (5 of 6) of the negative samples. Anaerobic and fastidious organisms may play a more significant role in osteomyelitis than previously reported. Further studies with larger populations are needed in order to fully understand the clinical importance of the microbial diversity of diabetic foot osteomyelitis.

[The Health-Related Quality of Life as Measured with the SF-12v1 in Elderly People Living in Luebeck 2010/11 in Comparison with the German Norm Data in 1994]. / Die bevölkerungsbezogene Lebensqualität gemessen mit dem SF-12v1 bei 51- bis 80-jährigen Lübeckern in den Jahren 2010/11 im Vergleich zur Deutschen Normstichprobe von 1994.

BACKGROUND: Health-related quality of life (HRQL) is deemed to be a meaningful endpoint when evaluating therapy and prevention interventions. For comparison purposes not only patient data but also representative population samples can serve as reference data. We aim to describe differences between the Luebeck population sample (LBS, year 2010/11) and the German norm population from 1994. Moreover, the influence of diabetes mellitus and hypertension on HRQL is analysed. METHODS: The LBS is a representative sample of 10 000 elderly people living in Luebeck aged 51-80 years, an age group susceptible to chronic diseases. Not only the SF-12v1, but also the item "actual health status in comparison to the last year" of the SF-36 and a list of comorbidities have been applied. Descriptive statistics are given for age, sex and disease groups. A comparison with data from the DNSP going back to 1994 is made using unstandardised data as well as age- and gender-standardised data. RESULTS: 5 835 individuals (response rate 60%) did participate in the survey (48% male, mean age 63.9 years, SD 7.7). PSC and MSC could be computed for 80% of them. Unstandardised values are 44.3±10.8 for the PSC and 50.4±10.3 for the MSC. Applying standardisation by age and gender, PSC values were comparable between the LBS and DNSP (except for the age group 51-60 years). MSC values were significantly lower in the LBS. The "general health Status" does not significantly differ whereas the "actual health status in comparison to the last year" is significantly lower in the LBS than in the DNSP (p<0.001). CONCLUSIONS: The LBS comprises more individuals than older studies in an age group relevant for chronic diseases. RESULTS hint to a comparable physical HRQL but a worse mental HRQL in the current data set. It remains unclear why persons between 51 and 60 years assess their physical HRQL worse than in the DNSP. A further open question is why the "actual health status in comparison to the last year" is assessed more negatively. Changed context conditions in working and social life may have an influence.