Predictions for the future of kallikrein-related peptidases in molecular diagnostics

Kallikrein-related peptidases (KLKs) form a cancer-related ensemble of serine proteases. This multigene family hosts the most widely used cancer biomarker that is PSA-KLK3, with millions of tests performed annually worldwide. The present report provides an overview of the biomarker potential of the extended KLK family (KLK1-KLK15) in various disease settings and envisages approaches that could lead to additional KLK-driven applications in future molecular diagnostics. Particular focus is given on the inclusion of KLKs into multifaceted cancer biomarker panels that provide enhanced diagnostic, prognostic and/or predictive accuracy in several human malignancies. Such panels have been described so far for prostate, ovarian, lung and colorectal cancers. The role of KLKs as biomarkers in non-malignant disease settings, such as Alzheimer’s disease and multiple sclerosis, is also commented upon. Predictions are given on the challenges and future directions regarding clinically oriented KLK research

Efficacy and safety of acupuncture for the treatment of non-specific acute low back pain: a randomised controlled multicentre trial protocol [ISRCTN65814467]

BACKGROUND: Low back pain and its associated incapacitating effects constitute an important healthcare and socioeconomic problem, as well as being one of the main causes of disability among adults of working age. The prevalence of non-specific low back pain is very high among the general population, and 60–70% of adults are believed to have suffered this problem at some time. Nevertheless, few randomised clinical trials have been made of the efficacy and efficiency of acupuncture with respect to acute low back pain. The present study is intended to assess the efficacy of acupuncture for acute low back pain in terms of the improvement reported on the Roland Morris Questionnaire (RMQ) on low back pain incapacity, to estimate the specific and non-specific effects produced by the technique, and to carry out a cost-effectiveness analysis. METHODS/DESIGN: Randomised four-branch controlled multicentre prospective study made to compare semi-standardised real acupuncture, sham acupuncture (acupuncture at non-specific points), placebo acupuncture and conventional treatment. The patients are blinded to the real, sham and placebo acupuncture treatments. Patients in the sample present symptoms of non specific acute low back pain, with a case history of 2 weeks or less, and will be selected from working-age patients, whether in paid employment or not, referred by General Practitioners from Primary Healthcare Clinics to the four clinics participating in this study. In order to assess the primary and secondary result measures, the patients will be requested to fill in a questionnaire before the randomisation and again at 3, 12 and 48 weeks after starting the treatment. The primary result measure will be the clinical relevant improvement (CRI) at 3 weeks after randomisation. We define CRI as a reduction of 35% or more in the RMQ results. DISCUSSION: This study is intended to obtain further evidence on the effectiveness of acupuncture on acute low back pain and to isolate the specific and non-specific effects of the treatment

Copeptin for risk stratification in non-traumatic headache in the emergency setting: a prospective multicenter observational cohort study

In the emergency setting, non-traumatic headache is a benign symptom in 80% of cases, but serious underlying conditions need to be ruled out. Copeptin improves risk stratification in several acute diseases. Herein, we investigated the value of copeptin to discriminate between serious secondary headache and benign headache forms in the emergency setting.; Patients presenting with acute non-traumatic headache were prospectively enrolled into an observational cohort study. Copeptin was measured upon presentation to the emergency department. Primary endpoint was serious secondary headache defined by a neurologic cause requiring immediate treatment of the underlying disease. Secondary endpoint was the combination of mortality and hospitalization within 3 months. Two board-certified neurologist blinded to copeptin levels verified the endpoints after a structured 3-month-telephone interview.; Of the 391 patients included, 75 (19%) had a serious secondary headache. Copeptin was associated with serious secondary headache (OR 2.03, 95%CI 1.52-2.70, p < 0.0001). Area under the curve (AUC) for copeptin to identify the primary endpoint was 0.70 (0.63-0.76). After adjusting for age > 50, focal-neurological abnormalities, and thunderclap onset of symptoms, copeptin remained an independent predictive factor for serious secondary headache (OR 1.74, 95%CI 1.26-2.39, p = 0.001). Moreover, copeptin improved the AUC of the multivariate logistic clinical model (p-LR-test < 0.001). Even though copeptin values were higher in patients reaching the secondary endpoint, this association was not significant in multivariate logistic regression.; Copeptin was independently associated with serious secondary headache as compared to benign headaches forms. Copeptin may be a promising novel blood biomarker that should be further validated to rule out serious secondary headache in the emergency department.; Study Registration on 08/02/2010 as NCT01174901 at clinicaltrials.gov

The influence of early aging on eye movements during motor simulation

Movement based interventions such as imagery and action observation are used increasingly to support physical rehabilitation of adults during early aging. The efficacy of these more covert approaches is based on an intuitively appealing assumption that movement execution, imagery and observation share neural substrate; alteration of one influences directly the function of the other two. Using eye movement metrics this paper reports findings that question the congruency of the three conditions. The data reveal that simulating movement through imagery and action observation may offer older adults movement practice conditions that are not constrained by the age-related decline observed in physical conditions. In addition, the findings provide support for action observation as a more effective technique for movement reproduction in comparison to imagery. This concern for imagery was also seen in the less congruent temporal relationship in movement time between imagery and movement execution suggesting imagery inaccuracy in early aging

A water-based training program that include perturbation exercises to improve stepping responses in older adults: study protocol for a randomized controlled cross-over trial

<p>Abstract</p> <p>Background</p> <p>Gait and balance impairments may increase the risk of falls, the leading cause of accidental death in the elderly population. Fall-related injuries constitute a serious public health problem associated with high costs for society as well as human suffering. A rapid step is the most important protective postural strategy, acting to recover equilibrium and prevent a fall from initiating. It can arise from large perturbations, but also frequently as a consequence of volitional movements. We propose to use a novel water-based training program which includes specific perturbation exercises that will target the stepping responses that could potentially have a profound effect in reducing risk of falling. We describe the water-based balance training program and a study protocol to evaluate its efficacy (Trial registration number #NCT00708136).</p> <p>Methods/Design</p> <p>The proposed water-based training program involves use of unpredictable, multi-directional perturbations in a group setting to evoke compensatory and volitional stepping responses. Perturbations are made by pushing slightly the subjects and by water turbulence, in 24 training sessions conducted over 12 weeks. Concurrent cognitive tasks during movement tasks are included. Principles of physical training and exercise including awareness, continuity, motivation, overload, periodicity, progression and specificity were used in the development of this novel program. Specific goals are to increase the speed of stepping responses and improve the postural control mechanism and physical functioning. A prospective, randomized, cross-over trial with concealed allocation, assessor blinding and intention-to-treat analysis will be performed to evaluate the efficacy of the water-based training program. A total of 36 community-dwelling adults (age 65–88) with no recent history of instability or falling will be assigned to either the perturbation-based training or a control group (no training). Voluntary step reaction times and postural stability using stabiliogram diffusion analysis will be tested before and after the 12 weeks of training.</p> <p>Discussion</p> <p>This study will determine whether a water-based balance training program that includes perturbation exercises, in a group setting, can improve speed of voluntary stepping responses and improve balance control. Results will help guide the development of more cost-effective interventions that can prevent the occurrence of falls in the elderly.</p

The genome sequence of E. coli W (ATCC 9637): comparative genome analysis and an improved genome-scale reconstruction of E. coli

Background: Escherichia coli is a model prokaryote, an important pathogen, and a key organism for industrial biotechnology. E. coli W (ATCC 9637), one of four strains designated as safe for laboratory purposes, has not been sequenced. E. coli W is a fast-growing strain and is the only safe strain that can utilize sucrose as a carbon source. Lifecycle analysis has demonstrated that sucrose from sugarcane is a preferred carbon source for industrial bioprocesses

A systematic review of non-invasive modalities used to identify women with anal incontinence symptoms after childbirth

© 2018, The International Urogynecological Association. Introduction and hypothesis: Anal incontinence following childbirth is prevalent and has a significant impact upon quality of life (QoL). Currently, there is no standard assessment for women after childbirth to identify these symptoms. This systematic review aimed to identify non-invasive modalities used to identify women with anal incontinence following childbirth and assess response and reporting rates of anal incontinence for these modalities. Methods: Ovid Medline, Allied and Complementary Medicine Database (AMED), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Cochrane Collaboration, EMBASE and Web of Science databases were searched for studies using non-invasive modalities published from January 1966 to May 2018 to identify women with anal incontinence following childbirth. Study data including type of modality, response rates and reported prevalence of anal incontinence were extracted and critically appraised. Results: One hundred and nine studies were included from 1602 screened articles. Three types of non-invasive modalities were identified: validated questionnaires/symptom scales (n = 36 studies using 15 different instruments), non-validated questionnaires (n = 50 studies) and patient interviews (n = 23 studies). Mean response rates were 92% up to 6 weeks after childbirth. Non-personalised assessment modalities (validated and non-validated questionnaires) were associated with reporting of higher rates of anal incontinence compared with patient interview at all periods of follow-up after childbirth, which was statistically significant between 6 weeks and 1 year after childbirth (p < 0.05). Conclusions: This systematic review confirms that questionnaires can be used effectively after childbirth to identify women with anal incontinence. Given the methodological limitations associated with non-validated questionnaires, assessing all women following childbirth for pelvic-floor symptomatology, including anal incontinence, using validated questionnaires should be considered

The Immunomodulatory Effect of Antibiotics on the Secretion of Tumour Necrosis Factor Alpha by Peripheral Blood Mononuclear Cells in Response to Stenotrophomonas maltophilia Stimulation

Some antibiotics have been shown to modify the host immune response. Infection with Stenotrophomonas maltophilia, is often difficult to treat due to multiresistance to antibiotics. The authors examined the effect of four commonly used antimicrobial agents (ciprofloxacin, ceftazidime, cotrimoxazole and piperacillin-tazobactam) on tumour necrosis factor alpha (TNF α) production by human peripheral blood mononuclear cells (PBMC) stimulated with heat-killed S maltophilia. Cotrimoxazole was the only antibiotic that suppressed TNF αsecretion at clinically achievable concentrations. This may explain its use with good effect in the treatment of S maltophilia infections. However at supratherapeutic concentrations, ceftazidime and ciprofloxacin, but not piperacillin-tazobactam, also inhibited significantly the production of TNF α. Cotrimoxazole, in addition to its antimicrobial effect against S maltophilia, has an immunomodulatory effect on peripheral blood mononuclear cells stimulated by S maltophilia. "Efecto Inmunomodulatorio de los Antibióticos Sobre la Secreción del Factor de Necrosis Tumoral Alfa por Células Sanguíneas Mononucleares Periféricas en Respuesta a la Estimulación de Stenotrophomonas Maltophilia" RESUMEN Algunos antibióticos han mostrado ser capaces de modificar la respuesta inmune del huésped. Las infecciones con Stenotrophomonas maltophilia – un patógeno emergente – son difíciles de tratar debido a su multiresistencia a los antibióticos. Examinamos el efecto de cuatro agentes antimicrobianos comúnmente usados (ciprofloxacina, ceftazidima, cotrimoxazol, y piperacilina-tazobactam) sobre la producción del factor de necrosis tumoral alfa (FNT α) por las células sanguíneas mononucleares periféricas humanas (PBMC) estimuladas con S maltophilia inactivadas mediante calor. El cotrimoxazol – en concentraciones clínicamente posibles – fue el único antibiótico que eliminó la secreción FNT α. Esto puede explicar su uso efectivo en el tratamiento de las infecciones por S maltophilia. Sin embargo, en concentraciones supraterapéuticas, la ceftazidima y la cipro-floxacina – pero no la piperacilina- tazobactam – también inhibieron significativamente la producción de FNT α. El cotrimoxazol, además de su efecto antimicrobiano contra S maltophilia, tiene un efecto inmuno-modulatorio sobre las células sanguíneas mononucleares periféricas estimuladas por S maltophilia