The role of postoperative prophylactic antibiotics in the treatment of facial fractures: a randomized, double-blind, placebo-controlled pilot clinical study. Part 2: mandibular fractures in 59 patients

The aim of this study was to evaluate the difference between a 5-day and a 1-day postoperative course of antibiotic on the incidence of infection after mandibular fractures involving the alveolus. Sixty-two patients with fractures of the mandible involving the dentoalveolar region were randomly assigned to 2 groups, both of which were given amoxicillin/clavulanic acid 1.2 g intravenously every 8 h from admission until 24 h postoperatively. The 5-day group were then given amoxicillin/clavulanic acid 625 mg orally every 8 h for another 4 days. The 1-day group was given an oral placebo at the same intervals. Follow-up appointments were 1, 2, 4, 6, 12 weeks and 6 months postoperatively. Development of an infection was the primary end point. Fifty-nine of the 62 patients completed this study. Six of the 30 patients in the 5-day group (20%) and 6 out of the 29 in the 1-day group (21%) developed local wound infections. Three of the 6 in the 1-day group developed purulent discharge and swelling. One patient in the 5-day group developed a rash on the trunk. There were no significant differences in the incidence of infection or side effects between the groups. In fractures of the mandible involving the alveolus, a 1-day postoperative course of antibiotic is as effective in preventing infective complications as a 5-day regimen.

Multifocal posterior uveitis in Crohn's disease

PURPOSE To report a case of rare posterior eye manifestation of Crohn's disease preceding recurrence of inflammatory bowel disease. METHODS Case report with ophthalmoscopic findings, fluorescein/indocyanin green angiograms, automated perimetry and multifocal-ERG. RESULTS The perimetry revealed absolute and relative scotomas corresponding to multifocal inflammatory lesions in the retina and choroid, reduced a/b amplitudes in multifocal-ERG and hypofluorescent dots in angiography. Under oral prednisolone visual defects, ophthalmoscopic and angiographic findings resolved, while a/b amplitudes remained mildly reduced. The ocular changes occurred without systemic hypertension and were followed by a new episode of intestinal symptoms. CONCLUSION Multifocal inflammatory lesions in the retina and choroid in patients with Crohn's disease may occur and may precede a recurrent intestinal episode. Crohn's patients should be carefully followed up in collaboration with internal medicine specialists.

Complex visual hallucinations and attentional performance in eye disease and dementia: a test of the Perception and Attention Deficit model

OBJECTIVE This study aimed to test the prediction from the Perception and Attention Deficit model of complex visual hallucinations (CVH) that impairments in visual attention and perception are key risk factors for complex hallucinations in eye disease and dementia. METHODS Two studies ran concurrently to investigate the relationship between CVH and impairments in perception (picture naming using the Graded Naming Test) and attention (Stroop task plus a novel Imagery task). The studies were in two populations-older patients with dementia (n = 28) and older people with eye disease (n = 50) with a shared control group (n = 37). The same methodology was used in both studies, and the North East Visual Hallucinations Inventory was used to identify CVH. RESULTS A reliable relationship was found for older patients with dementia between impaired perceptual and attentional performance and CVH. A reliable relationship was not found in the population of people with eye disease. CONCLUSIONS The results add to previous research that object perception and attentional deficits are associated with CVH in dementia, but that risk factors for CVH in eye disease are inconsistent, suggesting that dynamic rather than static impairments in attentional processes may be key in this population.

Short-term response of the Ca cycle of a montane forest in Ecuador to low experimental CaCl 2 additions

The tropical montane forests of the E Andean cordillera in Ecuador receive episodic Sahara-dust inputs particularly increasing Ca deposition. We added CaCl2 to isolate the effect of Ca deposition by Sahara dust to tropical montane forest from the simultaneously occurring pH effect. We examined components of the Ca cycle at four control plots and four plots with added Ca (2 × 5 kg ha–1 Ca annually as CaCl2) in a random arrangement. Between August 2007 and December 2009 (four applications of Ca), we determined Ca concentrations and fluxes in litter leachate, mineral soil solution (0.15 and 0.30 m depths), throughfall, and fine litterfall and Al concentrations and speciation in soil solutions. After 1 y of Ca addition, we assessed fine-root biomass, leaf area, and tree growth. Only < 3% of the applied Ca leached below the acid organic layer (pH 3.5–4.8). The added CaCl2 did not change electrical conductivity in the root zone after 2 y. In the second year of fertilization, Ca retention in the canopy of the Ca treatment tended to decrease relative to the control. After 2 y, 21% of the applied Ca was recycled to soil with throughfall and litterfall. One year after the first Ca addition, fine-root biomass had decreased significantly. Decreasing fine-root biomass might be attributed to a direct or an indirect beneficial effect of Ca on the soil decomposer community. Because of almost complete association of Al with dissolved organic matter and high free Ca2+ : Al3+ activity ratios in solution of all plots, Al toxicity was unlikely. We conclude that the added Ca was retained in the system and had beneficial effects on some plants.

Illegitimate tasks associated with higher cortisol levels among male employees when subjective health is relatively low: an intra-individual analysis

Objectives Illegitimate tasks refer to tasks that do not conform to what can appropriately be expected from an employee. Violating role expectations, they constitute “identity-stressors”, as one’s professional role tends to become part of one’s identity. The current study investigated the impact of illegitimate tasks on salivary cortisol. We analyzed data on an intra-individual level, that is, by examining fluctuations in illegitimate tasks and cortisol within individuals. Furthermore, we investigated the moderating role of perceived health, expecting that illegitimate tasks evoke stronger reactions when perceived health is relatively poor. Methods Illegitimate tasks, salivary cortisol, and perceived health were assessed in each of three waves (time lag: 6 months) in a sample of 104 male employees. Data were analyzed by multilevel analysis using group mean centering. Results Controlling for social stressors, work interruptions, and emotional stability, the experience of more illegitimate tasks was associated with increased cortisol release if personal health resources were low compared to one’s mean value of perceived health. Results cannot be explained by inter-individual differences. Conclusions This is the first study showing that illegitimate tasks predict a biological indicator of stress, thus confirming and extending previous research on illegitimate tasks. The moderating role of perceived health confirms its importance as a personal resource, implying augmented vulnerability when perceived health is below its usual value. It is plausible to assume that increased stress reactions due to relatively poor health may further weaken available personal resources. Both avoiding illegitimate tasks and restoring personal health seem to be crucial.

Distinct microRNA Expression Profile in Prostate Cancer Patients with Early Clinical Failure and the Impact of let-7 as Prognostic Marker in High-Risk Prostate Cancer

Background The identification of additional prognostic markers to improve risk stratification and to avoid overtreatment is one of the most urgent clinical needs in prostate cancer (PCa). MicroRNAs, being important regulators of gene expression, are promising biomarkers in various cancer entities, though the impact as prognostic predictors in PCa is poorly understood. The aim of this study was to identify specific miRNAs as potential prognostic markers in high-risk PCa and to validate their clinical impact. Methodology and Principal Findings We performed miRNA-microarray analysis in a high-risk PCa study group selected by their clinical outcome (clinical progression free survival (CPFS) vs. clinical failure (CF)). We identified seven candidate miRNAs (let-7a/b/c, miR-515-3p/5p, -181b, -146b, and -361) that showed differential expression between both groups. Further qRT-PCR analysis revealed down-regulation of members of the let-7 family in the majority of a large, well-characterized high-risk PCa cohort (n = 98). Expression of let-7a/b/and -c was correlated to clinical outcome parameters of this group. While let-7a showed no association or correlation with clinical relevant data, let-7b and let-7c were associated with CF in PCa patients and functioned partially as independent prognostic marker. Validation of the data using an independent high-risk study cohort revealed that let-7b, but not let-7c, has impact as an independent prognostic marker for BCR and CF. Furthermore, we identified HMGA1, a non-histone protein, as a new target of let-7b and found correlation of let-7b down-regulation with HMGA1 over-expression in primary PCa samples. Conclusion Our findings define a distinct miRNA expression profile in PCa cases with early CF and identified let-7b as prognostic biomarker in high-risk PCa. This study highlights the importance of let-7b as tumor suppressor miRNA in high-risk PCa and presents a basis to improve individual therapy for high-risk PCa patients.

MiR-205 is progressively down-regulated in lymph node metastasis but fails as a prognostic biomarker in high-risk prostate cancer

The treatment of high-risk prostate cancer (HRPCa) is a tremendous challenge for uro-oncologists. The identification of predictive moleculobiological markers allowing risk assessment of lymph node metastasis and systemic progression is essential in establishing effective treatment. In the current study, we investigate the prognostic potential of miR-205 in HRPCa study and validation cohorts, setting defined clinical endpoints for both. We demonstrate miR-205 to be significantly down-regulated in over 70% of the HRPCa samples analysed and that reconstitution of miR-205 causes inhibition of proliferation and invasiveness in prostate cancer (PCa) cell lines. Additionally, miR-205 is increasingly down-regulated in lymph node metastases compared to the primary tumour indicating that miR-205 plays a role in migration of PCa cells from the original location into extraprostatic tissue. Nevertheless, down-regulation of miR-205 in primary PCa was not correlated to the synchronous presence of metastasis and failed to predict the outcome for HRPCa patients. Moreover, we found a tendency for miR-205 up-regulation to correlate with an adverse outcome of PCa patients suggesting a pivotal role of miR-205 in tumourigenesis. Overall, we showed that miR-205 is involved in the development and metastasis of PCa, but failed to work as a useful clinical biomarker in HRPCa. These findings might have implications for the use of miR-205 as a prognostic or therapeutic target in HRPCa.

Mechanism for active membrane fusion triggering by morbillivirus attachment protein.

The paramyxovirus entry machinery consists of two glycoproteins that tightly cooperate to achieve membrane fusion for cell entry: the tetrameric attachment protein (HN, H, or G, depending on the paramyxovirus genus) and the trimeric fusion protein (F). Here, we explore whether receptor-induced conformational changes within morbillivirus H proteins promote membrane fusion by a mechanism requiring the active destabilization of prefusion F or by the dissociation of prefusion F from intracellularly preformed glycoprotein complexes. To properly probe F conformations, we identified anti-F monoclonal antibodies (MAbs) that recognize conformation-dependent epitopes. Through heat treatment as a surrogate for H-mediated F triggering, we demonstrate with these MAbs that the morbillivirus F trimer contains a sufficiently high inherent activation energy barrier to maintain the metastable prefusion state even in the absence of H. This notion was further validated by exploring the conformational states of destabilized F mutants and stabilized soluble F variants combined with the use of a membrane fusion inhibitor (3g). Taken together, our findings reveal that the morbillivirus H protein must lower the activation energy barrier of metastable prefusion F for fusion triggering.

Experimental adaptation of wild-type canine distemper virus (CDV) to the human entry receptor CD150.

Canine distemper virus (CDV), a close relative of measles virus (MV), is widespread and well known for its broad host range. When the goal of measles eradication may be achieved, and when measles vaccination will be stopped, CDV might eventually cross the species barrier to humans and emerge as a new human pathogen. In order to get an impression how fast such alterations may occur, we characterized required adaptive mutations to the human entry receptors CD150 (SLAM) and nectin-4 as first step to infect human target cells. Recombinant wild-type CDV-A75/17(red) adapted quickly to growth in human H358 epithelial cells expressing human nectin-4. Sequencing of the viral attachment proteins (hemagglutinin, H, and fusion protein, F) genes revealed that no adaptive alteration was required to utilize human nectin-4. In contrast, the virus replicated only to low titres (10(2) pfu/ml) in Vero cells expressing human CD150 (Vero-hSLAM). After three passages using these cells virus was adapted to human CD150 and replicated to high titres (10(5) pfu/ml). Sequence analyses revealed that only one amino acid exchange in the H-protein at position 540 Asp→Gly (D540G) was required for functional adaptation to human CD150. Structural modelling suggests that the adaptive mutation D540G in H reflects the sequence alteration from canine to human CD150 at position 70 and 71 from Pro to Leu (P70L) and Gly to Glu (G71E), and compensates for the gain of a negative charge in the human CD150 molecule. Using this model system our data indicate that only a minimal alteration, in this case one adaptive mutation, is required for adaptation of CDV to the human entry receptors, and help to understand the molecular basis why this adaptive mutation occurs.

Virtual Cilicia Project. How to use Google Earth as a visualization environment in an archaeological context

Over the past few years, archaeology has experienced a rapid development in geophysical prospection and remote sensing techniques. At the same time, the focus of archaeological research has shifted to landscape evelopment and human interaction. To impart the results, new methods and techniques are necessary. Virtual globes such as Google Earth offer fascinating methods of giving interested amateurs the possibility to interactively explore ancient cities and landscapes. Thanks to the increasing usage of GIS in cultural heritage, the implementation of interactive three dimensional learning opportunities becomes less and less tedious, but the non-linear narrative story telling medium demands for a special adaption of the content. This paper summarizes the experience gained during the realization of the “Virtual Cilicia Project” and outlines the future potential of virtual globes in the field of cultural heritage.

Hyaluronic Acid Levels Predict Risk of Hepatic Encephalopathy and Liver-Related Death in HIV/Viral Hepatitis Coinfected Patients

Background Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid’s (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study. Methods Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0–75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls). Results During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2–62.6) and 221.6 ng/mL (74.9–611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75–250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86–9.26, p<0.0007) and 28.22 (95% CI 14.95–46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR –5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001). Conclusions An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications.

Early re-do surgery for glioblastoma is a feasible and safe strategy to achieve complete resection of enhancing tumor.

BACKGROUND Complete resection of enhancing tumor as assessed by early (<72 hours) postoperative MRI is regarded as the optimal result in glioblastoma surgery. As yet, there is no consensus on standard procedure if post-operative imaging reveals unintended tumor remnants. OBJECTIVE The current study evaluated the feasibility and safety of an early re-do surgery aimed at completing resections with the aid of 5-ALA fluorescence and neuronavigation after detection of enhancing tumor remnants on post-operative MRI. METHODS From October 2008 to October 2012 a single center institutional protocol offered a second surgery within one week to patients with unintentional incomplete glioblastoma resection. We report on the feasibility of the use 5-ALA fluorescence guidance, the extent of resection (EOR) rates and complications of early re-do surgery. RESULTS Nine of 151 patients (6%) with glioblastoma resections had an unintentional tumor remnant with a volume >0.175 cm(3). 5-ALA guided re-do surgery completed the resection (CRET) in all patients without causing neurological deficits, infections or other complications. Patients who underwent a re-do surgery remained hospitalized between surgeries, resulting in a mean length of hospital stay of 11 days (range 7-15), compared to 9 days for single surgery (range 3-23; p=0.147). CONCLUSION Our early re-do protocol led to complete resection of all enhancing tumor in all cases without any new neurological deficits and thus provides a similar oncological result as intraoperative MRI (iMRI). The repeated use of 5-ALA induced fluorescence, used for identification of small remnants, remains highly sensitive and specific in the setting of re-do surgery. Early re-do surgery is a feasible and safe strategy to complete unintended subtotal resections.