New trends in peptide-based anti-biofilm strategies : a review of recent achievements and bioinformatics approaches

Antimicrobial peptides (AMPs) have a broad spectrum of activity and unspecific mechanisms of action. Therefore, they are seen as valid alternatives to overcome clinically relevant biofilms and reduce the chance of acquired resistance. This paper reviews AMPs and anti-biofilm AMP-based strategies and discusses ongoing and future work. Recent studies report successful AMP-based prophylactic and therapeutic strategies, several databases catalogue AMP information and analysis tools, and novel bioinformatics tools are supporting AMP discovery and design. However, most AMP studies are performed with planktonic cultures, and most studies on sessile cells test AMPs on growing rather than mature biofilms. Promising preliminary synergistic studies have to be consubstantiated and the study of functionalized coatings with AMPs must be further explored. Standardized operating protocols, to enforce the repeatability and reproducibility of AMP anti-biofilm tests, and automated means of screening and processing the ever-expanding literature are still missing.Financial support from IBB-CEB and Fundacao para a Ciencia e Tecnologia (FCT) and European Community fund FEDER, through Program COMPETE, in the ambit of the FCT project 'PTDC/SAU-SAP/113196/2009/ FCOMP-01-0124-FEDER-016012' is gratefully acknowledged

Early Clinical and Subclinical Visual Evoked Potential and Humphrey's Visual Field Defects in Cryptococcal Meningitis.

Cryptococcal induced visual loss is a devastating complication in survivors of cryptococcal meningitis (CM). Early detection is paramount in prevention and treatment. Subclinical optic nerve dysfunction in CM has not hitherto been investigated by electrophysiological means. We undertook a prospective study on 90 HIV sero-positive patients with culture confirmed CM. Seventy-four patients underwent visual evoked potential (VEP) testing and 47 patients underwent Humphrey's visual field (HVF) testing. Decreased best corrected visual acuity (BCVA) was detected in 46.5% of patients. VEP was abnormal in 51/74 (68.9%) right eyes and 50/74 (67.6%) left eyes. VEP P100 latency was the main abnormality with mean latency values of 118.9 (±16.5) ms and 119.8 (±15.7) ms for the right and left eyes respectively, mildly prolonged when compared to our laboratory references of 104 (±10) ms (p<0.001). Subclinical VEP abnormality was detected in 56.5% of normal eyes and constituted mostly latency abnormality. VEP amplitude was also significantly reduced in this cohort but minimally so in the visually unimpaired. HVF was abnormal in 36/47 (76.6%) right eyes and 32/45 (71.1%) left eyes. The predominant field defect was peripheral constriction with an enlarged blind spot suggesting the greater impact by raised intracranial pressure over that of optic neuritis. Whether this was due to papilloedema or a compartment syndrome is open to further investigation. Subclinical HVF abnormalities were minimal and therefore a poor screening test for early optic nerve dysfunction. However, early optic nerve dysfunction can be detected by testing of VEP P100 latency, which may precede the onset of visual loss in CM

Advanced adenoma diagnosis with FDG PET in a visibly normal mucosa: a case report

<p>Abstract</p> <p>Background</p> <p>An accurate, early diagnosis and treatment of adenomatous polyp can curtail progression to colorectal cancer. F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) reveals the biochemical changes associated with the development of many cancers which precede the appearance of gross anatomical changes that may be visualized during surgical resection or via imaging with MR or CT.</p> <p>Intervention</p> <p>We detail the history of a 64 year old female who had a whole-body FDG PET scan as a part of an employee wellness program. A dose of 12.2 mCi of F-18 labeled FDG was administered.</p> <p>Results</p> <p>A focal cecal uptake with a standardized uptake value (SUV) of 8.9 was found on the PET scan. Conversely, only normal mucosa was observed during a colonoscopy done 2 months after the PET scan. Motivated by the PET scan finding, the colonoscopist performed a biopsy which revealed a villous adenoma without high grade dysplasia. Pathology from tissue extracted during an exploratory laparatomy completed one month later found the lesion to be a villous adenoma with high grade dysplasia.</p> <p>Conclusion</p> <p>Whole-body FDG PET scan revealed the biochemical metabolic changes in malignancy that preceded the appearance of any gross anatomical abnormality. A positive FDG PET scan indicative of colorectal cancer should be followed up with a colonoscopy and biopsy even in a visibly normal mucosa.</p

Primary peritoneal and ovarian cancers: an epidemiological comparative analysis

We performed case–control analyses using data from the North Carolina Ovarian Cancer Study to determine risk factors that distinguish primary peritoneal cancer (PPC) from epithelial ovarian cancer (EOC). Our risk factor analyses were restricted to invasive serous cancers including 495 EOC cases, 62 PPC cases and 1,086 control women. Logistic regression analyses were used to calculate adjusted odds ratios and 95% confidence intervals for risk factor associations. Although many case–control associations for the invasive serous PPC cases were similar to those of the invasive serous EOC cases, some differences were observed including a twofold increase in risk of invasive serous PPC in women who were ≥35 years at last pregnancy, whereas a decreased risk was observed for invasive serous EOC risk. We could not confirm a previous report of an association between tubal ligation and PPC, a factor consistently associated with a decreased risk of EOC. The difference in the risk factor associations between invasive serous PPC and EOC cancers suggests divergent molecular development of peritoneal and ovarian cancers. A larger study to determine risk factors for invasive serous PPC is warranted

Potential climatic transitions with profound impact on Europe

We discuss potential transitions of six climatic subsystems with large-scale impact on Europe, sometimes denoted as tipping elements. These are the ice sheets on Greenland and West Antarctica, the Atlantic thermohaline circulation, Arctic sea ice, Alpine glaciers and northern hemisphere stratospheric ozone. Each system is represented by co-authors actively publishing in the corresponding field. For each subsystem we summarize the mechanism of a potential transition in a warmer climate along with its impact on Europe and assess the likelihood for such a transition based on published scientific literature. As a summary, the ‘tipping’ potential for each system is provided as a function of global mean temperature increase which required some subjective interpretation of scientific facts by the authors and should be considered as a snapshot of our current understanding. <br/

CT colonography with limited bowel preparation for the detection of colorectal neoplasia in an FOBT positive screening population

Item does not contain fulltextPURPOSE: Aim was to evaluate the accuracy of computed tomography colonography (CTC) for detection of colorectal neoplasia in a Fecal Occult Blood Test (FOBT) positive screening population. METHODS: In three different institutions, consecutive FOBT positives underwent CTC after laxative free iodine tagging bowel preparation followed by colonoscopy with segmental unblinding. Each CTC was read by two experienced observers. For CTC and for colonoscopy the per-polyp sensitivity and per-patient sensitivity and specificity were calculated for detection of carcinomas, advanced adenomas, and adenomas. RESULTS: In total 22 of 302 included FOBT positive participants had a carcinoma (7%) and 137 had an adenoma or carcinoma >/=10 mm (45%). CTC sensitivity for carcinoma was 95% with one rectal carcinoma as false negative finding. CTC sensitivity for advanced adenomas was 92% (95% CI: 88-96) vs. 96% (95% CI: 93-99) for colonoscopy (P = 0.26). For adenomas and carcinomas >/=10 mm the CTC per-polyp sensitivity was 93% (95% CI: 89-97) vs. 97% (95% CI: 94-99) for colonoscopy (P = 0.17). The per-patient sensitivity for the detection of adenomas and carcinomas >/=10 mm was 95% (95% CI: 91-99) for CTC vs. 99% (95% CI: 98-100) for colonoscopy (P = 0.07), while the per-patient specificity was 90% (95% CI: 86-95) and 96% (95% CI: 94-99), respectively (P < 0.001). CONCLUSION: CTC with limited bowel preparation performed in an FOBT positive screening population has high diagnostic accuracy for the detection of adenomas and carcinomas and a sensitivity similar to that of colonoscopy for relevant lesions.1 december 201

Catheter Related Bloodstream Infection (CR-BSI) in ICU Patients: Making the Decision to Remove or Not to Remove the Central Venous Catheter

Background Approximately 150 million central venous catheters (CVC) are used each year in the United States. Catheter-related bloodstream infections (CR-BSI) are one of the most important complications of the central venous catheters (CVCs). Our objective was to compare the in-hospital mortality when the catheter is removed or not removed in patients with CR-BSI. Methods We reviewed all episodes of CR-BSI that occurred in our intensive care unit (ICU) from January 2000 to December 2008. The standard method was defined as a patient with a CVC and at least one positive blood culture obtained from a peripheral vein and a positive semi quantitative (\u3e15 CFU) culture of a catheter segment from where the same organism was isolated. The conservative method was defined as a patient with a CVC and at least one positive blood culture obtained from a peripheral vein and one of the following: (1) differential time period of CVC culture versus peripheral culture positivity of more than 2 hours, or (2) simultaneous quantitative blood culture with 5:1 ratio (CVC versus peripheral). Results 53 CR-BSI (37 diagnosed by the standard method and 16 by the conservative method) were diagnosed during the study period. There was a no statistically significant difference in the in-hospital mortality for the standard versus the conservative method (57% vs. 75%, p = 0.208) in ICU patients. Conclusion In our study there was a no statistically significant difference between the standard and conservative methods in-hospital mortality

Invasive fungal disease in PICU: epidemiology and risk factors

Candida and Aspergillus spp. are the most common agents responsible for invasive fungal infections in children. They are associated with a high mortality and morbidity rate as well as high health care costs. An important increase in their incidence has been observed during the past two decades. In infants and children, invasive candidiasis is five times more frequent than invasive aspergillosis. Candida sp. represents the third most common agent found in healthcare-associated bloodstream infections in children. Invasive aspergillosis is more often associated with hematological malignancies and solid tumors. Recommendations concerning prophylactic treatment for invasive aspergillosis have been recently published by the Infectious Diseases Society of America. Candida albicans is the main Candida sp. associated with invasive candidiasis in children, even if a strong trend toward the emergence of Candida non-albicans has been observed. The epidemiology and the risk factors for invasive fungal infections are quite different if considering previously healthy children hospitalized in the pediatric intensive care unit, or children with a malignancy or a severe hematological disease (leukemia). In children, the mortality rate for invasive aspergillosis is 2.5 to 3.5 higher than for invasive candidiasis (respectively 70% vs. 20% and 30%)

The effect of an intracerebroventricular injection of metformin or AICAR on the plasma concentrations of melatonin in the ewe: potential involvement of AMPK?

<p>Abstract</p> <p>Background</p> <p>It is now widely accepted that AMP-activated protein kinase (AMPK) is a critical regulator of energy homeostasis. Recently, it has been shown to regulate circadian clocks. In seasonal breeding species such as sheep, the circadian clock controls the secretion of an endogenous rhythm of melatonin and, as a consequence, is probably involved in the generation of seasonal rhythms of reproduction. Considering this, we identified the presence of the subunits of AMPK in different hypothalamic nuclei involved in the pre- and post-pineal pathways that control seasonality of reproduction in the ewe and we investigated if the intracerebroventricular (i.c.v.) injection of two activators of AMPK, metformin and AICAR, affected the circadian rhythm of melatonin in ewes that were housed in constant darkness. In parallel the secretion of insulin was monitored as a peripheral metabolic marker. We also investigated the effects of i.c.v. AICAR on the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in brain structures along the photoneuroendocrine pathway to the pineal gland.</p> <p>Results</p> <p>All the subunits of AMPK that we studied were identified in all brain areas that were dissected but with some differences in their level of expression among structures. Metformin and AICAR both reduced (p < 0.001 and p < 0.01 respectively) the amplitude of the circadian rhythm of melatonin secretion independently of insulin secretion. The i.c.v. injection of AICAR only tended (p = 0.1) to increase the levels of phosphorylated AMPK in the paraventricular nucleus but significantly increased the levels of phosphorylated ACC in the paraventricular nucleus (p < 0.001) and in the pineal gland (p < 0.05).</p> <p>Conclusions</p> <p>Taken together, these results suggest a potential role for AMPK on the secretion of melatonin probably acting trough the paraventricular nucleus and/or directly in the pineal gland. We conclude that AMPK may act as a metabolic cue to modulate the rhythm of melatonin secretion.</p