Scintigraphic assessment of bone status at one year following hip resurfacing : comparison of two surgical approaches using SPECT-CT scan

Objectives: To study the vascularity and bone metabolism of the femoral head/neck following hip resurfacing arthroplasty, and to use these results to compare the posterior and the trochanteric-flip approaches. Methods: In our previous work, we reported changes to intra-operative blood flow during hip resurfacing arthroplasty comparing two surgical approaches. In this study, we report the vascularity and the metabolic bone function in the proximal femur in these same patients at one year after the surgery. Vascularity and bone function was assessed using scintigraphic techniques. Of the 13 patients who agreed to take part, eight had their arthroplasty through a posterior approach and five through a trochanteric-flip approach. Results: One year after surgery, we found no difference in the vascularity (vascular phase) and metabolic bone function (delayed phase) at the junction of the femoral head/neck between the two groups of patients. Higher radiopharmaceutical uptake was found in the region of the greater trochanter in the trochanteric-flip group, related to the healing osteotomy. Conclusions: Our findings using scintigraphic techniques suggest that the greater intra-operative reduction in blood flow to the junction of the femoral head/neck, which is seen with the posterior approach compared with trochanteric flip, does not result in any difference in vascularity or metabolic bone function one year after surgery

Antifungal Activity of Microbial Secondary Metabolites

Secondary metabolites are well known for their ability to impede other microorganisms. Reanalysis of a screen of natural products using the Caenorhabditis elegans-Candida albicans infection model identified twelve microbial secondary metabolites capable of conferring an increase in survival to infected nematodes. In this screen, the two compound treatments conferring the highest survival rates were members of the epipolythiodioxopiperazine (ETP) family of fungal secondary metabolites, acetylgliotoxin and a derivative of hyalodendrin. The abundance of fungal secondary metabolites indentified in this screen prompted further studies investigating the interaction between opportunistic pathogenic fungi and Aspergillus fumigatus, because of the ability of the fungus to produce a plethora of secondary metabolites, including the well studied ETP gliotoxin. We found that cell-free supernatant of A. fumigatus was able to inhibit the growth of Candida albicans through the production of a secreted product. Comparative studies between a wild-type and an A. fumigatus ΔgliP strain unable to synthesize gliotoxin demonstrate that this secondary metabolite is the major factor responsible for the inhibition. Although toxic to organisms, gliotoxin conferred an increase in survival to C. albicans-infected C. elegans in a dose dependent manner. As A. fumigatus produces gliotoxin in vivo, we propose that in addition to being a virulence factor, gliotoxin may also provide an advantage to A. fumigatus when infecting a host that harbors other opportunistic fungi

Caspase-2 Mediated Apoptotic and Necrotic Murine Macrophage Cell Death Induced by Rough Brucella abortus

Brucella species are Gram-negative, facultative intracellular bacteria that cause zoonotic brucellosis. Survival and replication inside macrophages is critical for establishment of chronic Brucella infection. Virulent smooth B. abortus strain 2308 inhibits programmed macrophage cell death and replicates inside macrophages. Cattle B. abortus vaccine strain RB51 is an attenuated rough, lipopolysaccharide O antigen-deficient mutant derived from smooth strain 2308. B. abortus rough mutant RA1 contains a single wboA gene mutation in strain 2308. Our studies demonstrated that live RB51 and RA1, but not strain 2308 or heat-killed Brucella, induced both apoptotic and necrotic cell death in murine RAW264.7 macrophages and bone marrow derived macrophages. The same phenomenon was also observed in primary mouse peritoneal macrophages from mice immunized intraperitoneally with vaccine strain RB51 using the same dose as regularly performed in protection studies. Programmed macrophage cell death induced by RB51 and RA1 was inhibited by a caspase-2 inhibitor (Z-VDVAD-FMK). Caspase-2 enzyme activation and cleavage were observed at the early infection stage in macrophages infected with RB51 and RA1 but not strain 2308. The inhibition of macrophage cell death promoted the survival of rough Brucella cells inside macrophages. The critical role of caspase-2 in mediating rough B. abortus induced macrophage cell death was confirmed using caspase-2 specific shRNA. The mitochondrial apoptosis pathway was activated in macrophages infected with rough B. abortus as demonstrated by increase in mitochondrial membrane permeability and the release of cytochrome c to cytoplasm in macrophages infected with rough Brucella. These results demonstrate that rough B. abortus strains RB51 and RA1 induce apoptotic and necrotic murine macrophage cell death that is mediated by caspase-2. The biological relevance of Brucella O antigen and caspase-2-mediated macrophage cell death in Brucella pathogenesis and protective Brucella immunity is discussed

Инфекционная составляющая и иммунопатология при хронических воспалительных заболеваниях слизистой оболочки гастродуоденальной области

Выявлено коинфицирование слизистой оболочки желудочно−кишечного тракта Helicobacter pylori и вирусами группы герпеса у больных хроническим гастритом, язвенной болезнью желудка и двенадцатиперстной кишки. Проведена оценка общих и специфических иммунных реакций организма на указанные инфекционные агенты. Обнаруженные изменения в клеточном и гуморальном звене иммунитета могут свидетельствовать об обусловленном ими системном иммунопатологическом процессе.Co−infection of the gastrointestinal mucosa with Helicobacter pylori and herpes viruses in patients with chronic gastritis, gastric and duodenal ulcer was revealed. General and specific immune reactions of the organism to the above agents were evaluated. The revealed changes in the cellular and humoral immunity can suggest systemic immunopathological process

A comparison of physicians and medical assistants in interpreting verbal autopsy interviews for allocating cause of neonatal death in Matlab, Bangladesh: can medical assistants be considered an alternative to physicians?

Objective. This study assessed the agreement between medical physicians in their interpretation of verbal autopsy (VA) interview data for identifying causes of neonatal deaths in rural Bangladesh. Methods. The study was carried out in Matlab, a rural sub-district in eastern Bangladesh. Trained persons conducted the VA interview with the mother or another family member at the home of the deceased. Three physicians and a medical assistant independently reviewed the VA interviews to assign causes of death using the International Classification of Diseases - Tenth Revision (ICD-10) codes. A physician assigned cause was decided when at least two physicians agreed on a cause of death. Cause-specific mortality fraction (CSMF), kappa (k) statistic, sensitivity, specificity, and positive predictive values were applied to compare agreement between the reviewers.Results. Of the 365 neonatal deaths reviewed, agreement on a direct cause of death was reached by at least two physicians in 339 (93%) of cases. Physician and medical assistant reviews of causes of death demonstrated the following levels of diagnostic agreement for the main causes of deaths: for birth asphyxia the sensitivity was 84%, specificity 93%, and kappa 0.77. For prematurity/low birth weight, the sensitivity, specificity, and kappa statistics were, respectively, 53%, 96%, and 0.55, for sepsis/meningitis they were 48%, 98%, and 0.53, and for pneumonia they were 75%, 94%, and 0.51. Conclusion. This study revealed a moderate to strong agreement between physician- assigned and medical assistant- assigned major causes of neonatal death. A well-trained medical assistant could be considered an alternative for assigning major causes of neonatal deaths in rural Bangladesh and in similar settings where physicians are scarce and their time costs more. A validation study with medically confirmed diagnosis will improve the performance of VA for assigning cause of neonatal death

The role of ligand efficiency metrics in drug discovery

The judicious application of ligand or binding efficiencies, which quantify the molecular properties required to gain binding affinity for a drug target, is gaining traction in the selection and optimisation of fragments, hits, and leads. Retrospective analysis of recently marketed oral drugs shows that they frequently have highly optimised ligand efficiency values for their target. Optimising ligand efficiencies based on both molecular size and lipophilicity, when set in the context of the specific target, has the potential to ameliorate the molecular inflation that pervades current practice in medicinal chemistry, and to increase the developability of drug candidates

An observational study to assess validity and reliability of smartphone sensor-based gait and balance assessments in multiple sclerosis: Floodlight GaitLab protocol

Background Gait and balance impairments are often present in people with multiple sclerosis (PwMS) and have a significant impact on quality of life and independence. Gold-standard quantitative tools for assessing gait and balance such as motion capture systems and force plates usually require complex technical setups. Wearable sensors, including those integrated into smartphones, offer a more frequent, convenient, and minimally burdensome assessment of functional disability in a home environment. We developed a novel smartphone sensor-based application (Floodlight) that is being used in multiple research and clinical contexts, but a complete validation of this technology is still lacking. Methods This protocol describes an observational study designed to evaluate the analytical and clinical validity of Floodlight gait and balance tests. Approximately 100 PwMS and 35 healthy controls will perform multiple gait and balance tasks in both laboratory-based and real-world environments in order to explore the following properties: (a) concurrent validity of the Floodlight gait and balance tests against gold-standard assessments; (b) reliability of Floodlight digital measures derived under different controlled gait and balance conditions, and different on-body sensor locations; (c) ecological validity of the tests; and (d) construct validity compared with clinician- and patient-reported assessments. Conclusions The Floodlight GaitLab study (ISRCTN15993728) represents a critical step in the technical validation of Floodlight technology to measure gait and balance in PwMS, and will also allow the development of new test designs and algorithms

A Visual Metaphor Describing Neural Dynamics in Schizophrenia

Background: In many scientific disciplines the use of a metaphor as an heuristic aid is not uncommon. A well known example in somatic medicine is the 'defense army metaphor' used to characterize the immune system. In fact, probably a large part of the everyday work of doctors consists of 'translating' scientific and clinical information (i.e. causes of disease, percentage of succes versus risk of side-effects) into information tailored to the needs and capacities of the individual patient. The ability to do so in an effective way is at least partly what makes a clinician a good communicator. Schizophrenia is a severe psychiatric disorder which affects approximately 1% of the population. Over the last two decades a large amount of molecular-biological, imaging and genetic data have been accumulated regarding the biological underpinnings of schizophrenia. However, it remains difficult to understand how the characteristic symptoms of schizophrenia such as hallucinations and delusions are related to disturbances on the molecular-biological level. In general, psychiatry seems to lack a conceptual framework with sufficient explanatory power to link the mental- and molecular-biological domains. Methodology/Principal Findings: Here, we present an essay-like study in which we propose to use visualized concepts stemming from the theory on dynamical complex systems as a 'visual metaphor' to bridge the mental- and molecular-biological domains in schizophrenia. We first describe a computer model of neural information processing; we show how the information processing in this model can be visualized, using concepts from the theory on complex systems. We then describe two computer models which have been used to investigate the primary theory on schizophrenia, the neurodevelopmental model, and show how disturbed information processing in these two computer models can be presented in terms of the visual metaphor previously described. Finally, we describe the effects of dopamine neuromodulation, of which disturbances have been frequently described in schizophrenia, in terms of the same visualized metaphor. Conclusions/Significance: The conceptual framework and metaphor described offers a heuristic tool to understand the relationship between the mental- and molecular-biological domains in an intuitive way. The concepts we present may serve to facilitate communicatio

Evaluating the organisational climate in Italian public healthcare institutions by means of a questionnaire

<p>Abstract</p> <p>Background</p> <p>By means of the ICONAS project, the Healthcare Agency of an Italian Region developed, and used a standardised questionnaire to quantify the organisational climate. The aims of the project were (a) to investigate whether the healthcare institutions were interested in measuring climate, (b) to estimate the range of applicability and reliability of the instrument, (c) to analyse the dimensions of climate among healthcare personnel, (d) to assess the differences among employees with different contractual positions.</p> <p>Methods</p> <p>The anonymous questionnaire containing 50 items, each with a scale from 1 to 10, was offered to the healthcare organisations, to be compiled during ad hoc meetings. The data were sent to the central project coordinator. The differences between highly specialised staff (mostly physicians) and other employees were assessed after descriptive statistical analysis of the single items. Both Principal Component Analysis and Factor Analysis were used.</p> <p>Results</p> <p>Ten healthcare organisations agreed to partecipate. The questionnaire was completed by 8691 employees out of 13202. The mean value of organisational climate was 4.79 (range 1–10). There were significant differences among single items and between the 2 groups of employees. Multivariate methods showed: (a) one principal component explained > 40% of the variance, (b) 7 factors summarised the data.</p> <p>Conclusion</p> <p>Italian healthcare institutions are interested in assessing organisational phenomena, especially after the reforms of the nineties. The instrument was found to be applicable and suitable for measuring organisational climate. Administration of the questionnaire leads to an acceptable response rate. Climate can be discribed by means of 7 underlying dimensions.</p

Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

We reconstruct the rare decays $B^+ \to K^+\mu^+\mu^-$, $B^0 \to K^{*}(892)^0\mu^+\mu^-$, and $B^0_s \to \phi(1020)\mu^+\mu^-$ in a data sample corresponding to $4.4 {\rm fb^{-1}}$ collected in $p\bar{p}$ collisions at $\sqrt{s}=1.96 {\rm TeV}$ by the CDF II detector at the Fermilab Tevatron Collider. Using $121 \pm 16$ $B^+ \to K^+\mu^+\mu^-$ and $101 \pm 12$ $B^0 \to K^{*0}\mu^+\mu^-$ decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the $B^+$ and $B^0$ decay modes, and the $K^{*0}$ longitudinal polarization in the $B^0$ decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the $B^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio${\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}$using$27 \pm 6$signal events. This is currently the most rare$B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let