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Global and local whole genome sequencing of SARS-CoV-2 enables the tracing of domestic and international transmissions. We sequenced Viral RNA from 37 sampled Covid-19 patients with RT-PCR-confirmed infections across the UAE and developed time-resolved phylogenies with 69 local and 3,894 global genome sequences. Furthermore, we investigated specific clades associated with the UAE cohort and, their global diversity, introduction events and inferred domestic and international virus transmissions between January and June 2020. The study comprehensively characterized the genomic aspects of the virus and its spread within the UAE and identified that the prevalence shift of the D614G mutation was due to the later introductions of the G-variant associated with international travel, rather than higher local transmissibility. For clades spanning different emirates, the most recent common ancestors pre-date domestic travel bans. In conclusion, we observe a steep and sustained decline of international transmissions immediately following the introduction of international travel restrictions.

Background Checkpoint inhibitors have revolutionized advanced melanoma care; however, their cutaneous side effects have not been definitively elucidated. Objective To identify the prevalence of cutaneous toxicity in patients with melanoma treated with immune checkpoint inhibitors as monotherapy and/or in combination with chemotherapy and/or radiotherapy. Materials and methods We performed a systematic review and meta-analysis, which encompassed both clinical trials and observational studies describing the dermatological toxicities in patients treated with immune checkpoint inhibitors. The protocol was registered in the International Prospective Register of Systematic Review under the number CRD42018091915. The searches were performed using the CINAHL, Cochrane CENTRAL, LILACS, LIVIVO, PubMed, Scopus, and Web of Science databases. The methodological quality of the studies was evaluated with the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data Results A total of 9,802 articles were identified in the databases. The final sample comprised 39 studies. The evaluated drugs were ipilimumab, tremelimumab, pembrolizumab, and nivolumab. The results suggest that the most prevalent side effect was grade 1 and 2 pruritus (24%), followed by grade 1 and 2 rash (21%) and grade 1 and 2 vitiligo (10%). Conclusion The most prevalent side effects in patients treated with checkpoint inhibitors are pruritus, rash, and vitiligo, and they are rated mostly as grades 1 and 2 adverse events. Remarkably, vitiligo is most commonly found in patients treated with PD-1 inhibitors.

Introduction Previous studies described impaired microvascular perfusion and tissue oxygenation as reliable predictors of Multiple Organ Failure in major trauma. However, this relationship has been incompletely investigated. The objective of this analysis is to further evaluate the association between organ dysfunction and microcirculation after trauma. Materials and methods This is a retrospective subgroup analysis on 28 trauma patients enrolled for the Microcirculation DAIly MONitoring in critically ill patients study (NCT 02649088). Patients were divided in two groups according with their Sequential Organ Failure Assessment (SOFA) score at day 4. At admission and every 24 hours, the sublingual microcirculation was evaluated with Sidestream Darkfield Imaging (SDF) and peripheral tissue perfusion was assessed with Near Infrared Spectroscopy (NIRS) and Vascular Occlusion Test (VOT). Simultaneously, hemodynamic, clinical/laboratory parameters and main organ supports were collected. Results Median SOFA score at Day 4 was 6.5. Accordingly, patients were divided in two groups: D4-SOFA ≤6.5 and D4-SOFA >6.5. The Length of Stay in Intensive Care was significantly higher in patients with D4-SOFA>6.5 compared to D4-SOFA≤6.5 (p = 0.013). Total Vessel Density of small vessels was significantly lower in patients with high D4-SOFA score at Day 1 (p = 0.002) and Day 2 (p = 0.006) after admission; the Perfused Vessel Density was lower in patients with high D4-SOFA score at Day 1 (p = 0.007) and Day 2 (p = 0.033). At Day 1, NIRS monitoring with VOT showed significantly faster tissue oxygen saturation downslope (p = 0.018) and slower upslope (p = 0.04) in patients with high D4-SOFA. Discussion In our cohort of major traumas, sublingual microcirculation and peripheral microvascular reactivity were significantly more impaired early after trauma in those patients who developed more severe organ dysfunctions. Our data would support the hypothesis that restoration of macrocirculation can be dissociated from restoration of peripheral and tissue perfusion, and that microvascular alterations can be associated with organ failure.

BackgroundThe use of medicinal plants and their derivatives is increasing, and approximately one-third of all traditional herbal medicines are intended for wound treatment. Natural products used in these treatments include vegetable oils, which are rich in essential fatty acids. Once in contact with an ulcerative surface, the oil reaches the blood and lymphatic vessels, thus eliciting systemic effects.ObjectiveThis study evaluated the local and possible systemic effects of essential fatty acids (sunflower oil) applied topically to rat wounds.MethodsCutaneous punch wounds (6 mm) were produced on the dorsa of 30 rats. Saline (SS), mineral oil (MO) or essential fatty acid (EFA) solutions were applied topically. Healing was evaluated after 2, 4 and 10 days (n = 5 per group) by visual and histological/morphometric examination, second harmonic generation (SHG) microscopy, and cytokine and growth factor quantification in the scar tissue (real-time PCR) and in serum (ELISA).ResultsMO/EFA-treated animals had higher IGF-1, leptin, IL-6 and IFN-γ mRNA expression and lower serum IL-6 levels than the control (SS/MO) animals. SHG analysis showed no difference in collagen density between the animals treated with MO and EFA.ConclusionEFA treatment induces topical (observed by local IGF-1, leptin, IL-6 and IFN-γ production) and systemic effects, lowering IL-6 levels in the serum. As the oil is widely used to shorten ulcer healing time, studies are needed to evaluate the treatment safety and possible undesired effects.

Objectives To analyze trajectories of cataract surgery rates and to confirm the switch between inpatient cases and day surgery or outpatient cases. Design Pooled, cross-sectional, time series analysis. Methods Data on 20 European countries from 2004 to 2014 retrieved from the OECD. Results The number of cataract surgery cases per 100,000 population has increased since 2004 (b = 31.1, p < 0.001, 95% CI = 26.7, 35.6). A reversal of the inpatient cases and same-day cases was found: the first ones decreased (b = –14.7, p < 0.001, 95% CI = –17.7, –11.8) while day surgery and outpatient cases increased (b = 37.5, p < 0.001, 95% CI = 31.6, 43.4, and b = 8.3, p = 0.001, 95% CI = 3.6, 13.1, respectively). Since 2004, the ratio of day surgery and outpatient cases to inpatient cases has grown significantly (b = 3.3, p < 0.001, 95% CI = 2.5, 4.0), reaching a share of 31.7 in 2014. However, this slope of 3.3 was not constant and slowed over the years: from 4.5 per year during the first five years to 1.9 in the second five. No association was found between cataract surgery rate and two regressors: elderly people, and health care expenditure per capita. Conclusion EU countries have preserved cataract surgery, and this preservation is probably affected by the switch from inpatient to same-day surgery, thanks to the decrease in the cost and equivalent clinical outcomes. However, the slope of the switch slowed over time. Consequently, health care systems must support this process of change especially through reforms in financial and organizational fields.

The expansion of primary care and community-based service delivery systems is intended to meet emerging needs, reduce the costs of hospital-based ambulatory care and prevent avoidable hospital use by the provision of more appropriate care. Great emphasis has been placed on the role of self-management in the complex process of care of patient with long-term conditions. Several studies have determined that nurses, among the health professionals, are more recommended to promote health and deliver preventive programs within the primary care context. The aim of this systematic review and meta-analysis is to assess the efficacy of the nurse-led self-management support versus usual care evaluating patient outcomes in chronic care community programs. Systematic review was carried out in MEDLINE, CINAHL, Scopus and Web of Science including RCTs of nurse-led self-management support interventions performed to improve observer reported outcomes (OROs) and patients reported outcomes (PROs), with any method of communication exchange or education in a community setting on patients >18 years of age with a diagnosis of chronic diseases or multi-morbidity. Of the 7,279 papers initially retrieved, 29 met the inclusion criteria. Meta-analyses on systolic (SBP) and diastolic (DBP) blood pressure reduction (10 studies-3,881 patients) and HbA1c reduction (7 studies-2,669 patients) were carried-out. The pooled MD were: SBP -3.04 (95% CI -5.01--1.06), DBP -1.42 (95% CI -1.42--0.49) and HbA1c -0.15 (95% CI -0.32-0.01) in favor of the experimental groups. Meta-analyses of subgroups showed, among others, a statistically significant effect if the interventions were delivered to patients with diabetes (SBP) or CVD (DBP), if the nurses were specifically trained, if the studies had a sample size higher than 200 patients and if the allocation concealment was not clearly defined. Effects on other OROs and PROs as well as quality of life remain inconclusive.

Objective To establish the diagnostic accuracy of magnetic resonance imaging (MRI) as an auxiliary means for the diagnosis of oral cancer through a systematic review and meta-analysis. Methods An exhaustive search of publications from 1986 to 2016 was performed of Medline, Embase and Cochrane (and related databases), including grey literature. Primary diagnostic accuracy studies that assessed oral cancer (target condition) using MRI (index test) were included. Diagnostic threshold, sensitivity and meta-regression analyses were performed. A meta-analysis was performed using Meta-DiSc® v. 1.4 software. Results A total of 24 primary studies were assessed, comprising 1,403 oral cancer lesions. Nine studies used diffusion-weighted MRI, with a diagnostic odds ratio (DOR) of 30.7 (95% confidence interval [CI]: 12.7-74.3) and area under the curve (AUC) of 0.917 (95% CI: 0.915-0.918); seven studies used dynamic contrast-enhanced MRI, with a DOR of 48.1 (95%CI: 22.4-103.2) and AUC of 0.936 (95% CI: 0.934-0.937); and 13 studies used traditional MRI, with a DOR of 23.9 (95%CI: 13.2-43.3) and AUC of 0.894 (95% CI: 0.894-0.895). Meta-regression analysis indicated that the magnetic field strength may have influenced the heterogeneity of the results obtained (p = 0.0233) using traditional MRI. Sensitivity analysis revealed a discrete reduction of inconsistency in some subgroups. Conclusion The three types of MRI assessed exhibited satisfactory accuracy compared to biopsy. Considering the relevance of early treatment and screening and that better health care results in improved survival rates and quality of life for oral cancer patients, we suggest the use of MRI as a part of the pre-treatment and monitoring protocol at public health services.

In germinating seeds under unfavorable environmental conditions, the mobilization of stores in the cotyledons is delayed, which may result in a different modulation of carbohydrates balance and a decrease in seedling vigor. Tall fescue (Festuca arundinacea Schreb.) caryopses grown at 4°C in the dark for an extended period in complete absence of nutrients, showed an unexpected ability to survive. Seedlings grown at 4°C for 210 days were morphologically identical to seedlings grown at 23°C for 21 days. After 400 days, seedlings grown at 4°C were able to differentiate plastids to chloroplast in just few days once transferred to the light and 23°C. Tall fescue exposed to prolonged period at 4°C showed marked anatomical changes: cell wall thickening, undifferentiated plastids, more root hairs and less xylem lignification. Physiological modifications were also observed, in particular related to sugar content, GA and ABA levels and amylolytic enzymes pattern. The phytohormones profiles exhibited at 4 and 23°C were comparable when normalized to the respective physiological states. Both the onset and the completion of germination were linked to GA and ABA levels, as well as to the ratio between these two hormones. All plants showed a sharp decline in carbohydrate content, with a consequent onset of gradual sugar starvation. This explained the slowed then full arrest in growth under both treatment regimes. The analysis of amylolytic activity showed that Ca2+ played a central role in the stabilization of several isoforms. Overall, convergence of starvation and hormone signals meet in crosstalk to regulate germination, growth and development in tall fescue.

Introduction Wounds are a common health problem. Coffee is widely consumed and its oil contains essential fatty acids. We evaluated the local (skin) and systemic effects associated with the topical use of coffee oils in rats. Methods Punch skin wounds (6 mm) incisions were generated on the backs of 75 rats. Saline (SS), mineral oil (MO), green coffee oil (GCO), roasted coffee oil (RCO), green coffee ground oil (GCGO) or roasted coffee ground oil (RCGO) were topically applied to the wounds. Healing was evaluated by visual and histological/morphometric optical microscopy examination; second harmonics generation (SHG) microscopy, wound tissue q-PCR (values in fold-change) and blood serum (ELISA, values in pg/mL). Results RCO treated animals presented faster wound healing (0.986 vs. 0.422), higher mRNA expression of IGF-1 (2.78 vs. 1.00, p = 0.01), IL-6 (10.72 vs. 1.00, p = 0.001) and IL-23 (4.10 vs. 1.2, p = 0.05) in early stages of wound healing; higher IL-12 (3.32 vs. 1.00, p = 0.05) in the later stages; and lower serum levels of IFN-γ (11.97 vs. 196.45, p = 0.01). GCO treatment led to higher mRNA expression of IL-6 (day 2: 7.94 vs. 1.00, p = 0.001 and day 4: 6.90 vs. 1.00, p = 0.01) and IL-23 (7.93 vs. 1.20, p = 0.001) in the early stages. The RCO treatment also produced higher serum IFN-α levels throughout the experiment (day 2: 52.53 vs. 21.20; day 4: 46.98 vs.21.56; day 10: 83.61 vs. 25.69, p = 0.05) and lower levels of IL-4 (day 4: 0.9 vs.13.36, p = 0.01), adiponectin (day 10: 8,367.47 vs. 16,526.38, p = 0.001) and IFN-γ (day 4: 43.03 vs.196.45, p = 0.05). The SHG analysis showed a higher collagen density in the RCO and GCO treatments (p = 0.05). Conclusion Topical treatment with coffee oils led to systemic actions and faster wound healing in rats. Further studies should be performed are necessary to assess the safety of topical vegetal oil use for skin lesions.

Background Free hemoglobin (fHb) may induce vasoconstriction by scavenging nitric oxide. It may increase in older blood units due to storage lesions. This study evaluated whether old red blood cell transfusion increases plasma fHb in sepsis and how the microvascular response may be affected. Methods This is a secondary analysis of a randomized study. Twenty adult septic patients received either fresh or old (15 days storage, respectively) RBC transfusions. fHb was measured in RBC units and in the plasma before and 1 hour after transfusion. Simultaneously, the sublingual microcirculation was assessed with sidestream-dark field imaging. The perfused boundary region was calculated as an index of glycocalyx damage. Tissue oxygen saturation (StO2) and Hb index (THI) were measured with near-infrared spectroscopy and a vascular occlusion test was performed. Results Similar fHb levels were found in the supernatant of fresh and old RBC units. Despite this, plasma fHb increased in the old RBC group after transfusion (from 0.125 [0.098–0.219] mg/mL to 0.238 [0.163–0.369] mg/mL, p = 0.006). The sublingual microcirculation was unaltered in both groups, while THI increased. The change in plasma fHb was inversely correlated with the changes in total vessel density (r = -0.57 [95% confidence interval -0.82, -0.16], p = 0.008), De Backer score (r = -0.63 [95% confidence interval -0.84, -0.25], p = 0.003) and THI (r = -0.72 [95% confidence interval -0.88, -0.39], p = 0.0003). Conclusions Old RBC transfusion was associated with an increase in plasma fHb in septic patients. Increasing plasma fHb levels were associated with decreased microvascular density. Trial Registration ClinicalTrials.gov NCT01584999

textabstractBackground: Italy has a population of 60 million and a universal coverage single-payer healthcare system, which mandates collection of healthcare administrative data in a uniform fashion throughout the country. On the other hand, organization of the health system takes place at the regional level, and local initiatives generate natural experiments. This is happening in particular in primary care, due to the need to face the growing burden of chronic diseases. Health services research can compare and evaluate local initiatives on the basis of the common healthcare administrative data.However reliability of such data in this context needs to be assessed, especially when comparing different regions of the country. In this paper we investigated the validity of healthcare administrative databases to compute indicators of compliance with standards of care for diabetes, ischaemic heart disease (IHD) and heart failure (HF). Methods: We compared indicators estimated from healthcare administrative data collected by Local Health Authorities in five Italian regions with corresponding estimates from clinical data collected by General Practitioners (GPs). Four indicators of diagnostic follow-up (two for diabetes, one for IHD and one for HF) and four indicators of appropriate therapy (two each for IHD and HF) were considered. Results: Agreement between the two data sources was very good, except for indicators of laboratory diagnostic follow-up in one region and for the indicator of bioimaging diagnostic follow-up in all regions, where measurement with administrative data underestimated quality. Conclusion: According to evidence presented in this study, estimating compliance with standards of care for diabetes, ischaemic heart disease and heart failure from healthcare databases is likely to produce reliable results, even though completeness of data on diagnostic procedures should be assessed first. Performing studies comparing regions using such indicators as outcomes is a promising development with potential to improve quality governance in the Italian healthcare system.

BACKGROUND: UVA rays present in sunlight are able to reach the dermal skin layer generating reactive oxygen species (ROS) responsible for oxidative damage, alterations in gene expression, DNA damage, leading to cell inflammation, photo-ageing/-carcinogenesis. Sunscreens contain UV filters as active ingredients that absorb/reflect/dissipate UV radiation: their efficiency depends on their spectral profile and photostability which should then be reflected in biological protection of underlying skin. METHODS: A set of new UV filters was synthesized, and the most photostable one was compared to BMDBM, a widely used UVA filter. Cultured human dermal fibroblasts were exposed to UVA radiation which was filtered by a base cream containing or not UV filters placed above cell culture wells. The endpoints measured were: cell viability (MTT assay), ROS generation (DCFH-DA assay), mitochondrial function (JC-1 assay), DNA integrity (Comet assay) and gene expression (MMP-1, COL1A1) by RT-qPCR. RESULTS: The new UV filter resulted more efficient than BMDBM in preserving cell viability, mitochondrial functionality and oxidative DNA damage, despite similar inhibition levels of intracellular ROS. Moreover, expression of genes involved in dermal photoageing were positively affected by the filtering action of the tested molecules. CONCLUSIONS: The experimental model proposed was able to validate the efficacy of the new UV filter, taking into account important cellular events related to UV-induced intracellular oxidative stress, often underestimated in the assessments of these compounds. GENERAL SIGNIFICANCE: The model may be used to compare the actual biological protection of commercial sunscreens and suncare products aside from their SPF and UVA-PF values.

Background The evidence of several forms of arthritis has been well documented in the fossil record. However, for pre-Cenozoic vertebrates, especially regarding reptiles, this record is rather scarce. In this work we present a case report of spondarthritis found in a vertebral series that belonged to a carnivorous archosaurian reptile from the Lower Triassic (~245 million years old) of the South African Karoo. Methodology/Principal Findings Neutron tomography confirmed macroscopic data, revealing the ossification of the entire intervertebral disc space (both annulus fibrosus and nucleus pulposus), which supports the diagnosis of spondarthritis. Conclusions/Significance The presence of spondarthritis in the new specimen represents by far the earliest evidence of any form of arthritis in the fossil record. The present find is nearly 100 million years older than the previous oldest report of this pathology, based on a Late Jurassic dinosaur. Spondarthritis may have indirectly contributed to the death of the animal under study.

BACKGROUND: Equine herpesvirus type 1 (EHV-1), a member of the Alphaherpesvirinae, is spread via nasal secretions and causes respiratory disease, neurological disorders and abortions. The virus is a significant equine pathogen, but current EHV-1 vaccines are only partially protective and effective metaphylactic and therapeutic agents are not available. Small interfering RNAs (siRNA's), delivered intranasally, could prove a valuable alternative for infection control. siRNA's against two essential EHV-1 genes, encoding the viral helicase (Ori) and glycoprotein B, were evaluated for their potential to decrease EHV-1 infection in a mouse model. METHODOLOGY/PRINCIPAL FNDINGS: siRNA therapy in vitro significantly reduced virus production and plaque size. Viral titers were reduced 80-fold with 37.5 pmol of a single siRNA or with as little as 6.25 pmol of each siRNA when used in combination. siRNA therapy in vivo significantly reduced viral replication and clinical signs. Intranasal treatment did not require a transport vehicle and proved effective when given up to 12 h before or after infection. CONCLUSIONS/SIGNIFICANCE: siRNA treatment has potential for both prevention and early treatment of EHV-1 infections.

Equine herpesvirus type 1 (EHV-1) causes respiratory disorders and abortion in equids while EHV-1 regularly causes equine herpesvirus myeloencephalopathy (EHM), a stroke-like syndrome following endothelial cell infection in horses. Both EHV-1 and EHV-9 infections of non-definitive hosts often result in neuronal infection and high case fatality rates. Hence, EHV-1 and EHV-9 are somewhat unusual herpesviruses and lack strict host specificity, and the true extent of their host ranges have remained unclear. In order to determine the seroprevalence of EHV-1 and EHV-9, a sensitive and specific peptide-based ELISA was developed and applied to 428 sera from captive and wild animals representing 30 species in 12 families and five orders. Members of the Equidae, Rhinocerotidae and Bovidae were serologically positive for EHV-1 and EHV-9. The prevalence of EHV-1 in the sampled wild zebra populations was significantly higher than in zoos suggesting captivity may reduce exposure to EHV-1. Furthermore, the seroprevalence for EHV-1 was significantly higher than for EHV-9 in zebras. In contrast, EHV-9 antibody prevalence was high in captive and wild African rhinoceros species suggesting that they may serve as a reservoir or natural host for EHV-9. Thus, EHV-1 and EHV-9 have a broad host range favoring African herbivores and may have acquired novel natural hosts in ecosystems where wild equids are common and are in close contact with other perissodactyls.

Background Several reports suggest that implementation of the Surviving Sepsis Campaign (SSC) guidelines is associated with mortality reduction in sepsis. However, adherence to the guideline-based resuscitation and management sepsis bundles is still poor. Objective To perform a systematic review of studies evaluating the impact of performance improvement programs on compliance with Surviving Sepsis Campaign (SSC) guideline-based bundles and/or mortality. Data Sources Medline (PubMed), Scopus and Intercollegiate Studies Institute Web of Knowledge databases from 2004 (first publication of the SSC guidelines) to October 2014. Study Selection Studies on adult patients with sepsis, severe sepsis or septic shock that evaluated changes in compliance to individual/combined bundle targets and/or mortality following the implementation of performance improvement programs. Interventions may consist of educational programs, process changes or both. Data Extraction Data from the included studies were extracted independently by two authors. Unadjusted binary data were collected in order to calculate odds ratios (OR) for compliance to individual/combined bundle targets. Adjusted (if available) or unadjusted data of mortality were collected. Random-effects models were used for the data synthesis. Results Fifty observational studies were selected. Despite high inconsistency across studies, performance improvement programs were associated with increased compliance with the complete 6-hour bundle (OR = 4.12 [95% confidence interval 2.95-5.76], I2 = 87.72%, k = 25, N = 50,081) and the complete 24-hour bundle (OR = 2.57 [1.74-3.77], I2 = 85.22%, k = 11, N = 45,846) and with a reduction in mortality (OR = 0.66 [0.61-0.72], I2 = 87.93%, k = 48, N = 434,447). Funnel plots showed asymmetry. Conclusions Performance improvement programs are associated with increased adherence to resuscitation and management sepsis bundles and with reduced mortality in patients with sepsis, severe sepsis or septic shock.

The yeast Wickerhamomyces anomalus has been investigated for several years for its wide biotechnological potential, especially for applications in the food industry. Specifically, the antimicrobial activity of this yeast, associated with the production of Killer Toxins (KTs), has attracted a great deal of attention. The strains of W. anomalus able to produce KTs, called "killer" yeasts, have been shown to be highly competitive in the environment. Different W. anomalus strains have been isolated from diverse habitats and recently even from insects. In the malaria mosquito vector Anopheles stephensi these yeasts have been detected in the midgut and gonads. Here we show that the strain of W. anomalus isolated from An. stephensi, namely WaF17.12, is a killer yeast able to produce a KT in a cell-free medium (in vitro) as well as in the mosquito body (in vivo). We showed a constant production of WaF17.12-KT over time, after stimulation of toxin secretion in yeast cultures and reintroduction of the activated cells into the mosquito through the diet. Furthermore, the antimicrobial activity of WaF17.12-KT has been demonstrated in vitro against sensitive microbes, showing that strain WaF17.12 releases a functional toxin. The mosquito-associated yeast WaF17.12 thus possesses an antimicrobial activity, which makes this yeast worthy of further investigations, in view of its potential as an agent for the symbiotic control of malaria.

IntroductionDelirium is a prevalent condition in patients admitted to intensive care units (ICU) associated with worse outcomes. The principal aim of the present study was compare the agreement between two tools for delirium assessment in medical and surgical patients admitted to the ICU.MethodsConsecutive adult surgical and medical patients admitted to the ICU for more than 24 hours between March 2009 and September 2010 were included. Delirium was evaluated twice a day using the Intensive Care Delirium Screening Checklist (ICDSC) and Confusion Assessment Method adapted to the Intensive Care Unit (CAM-ICU). The kappa (k) and AC1 coefficients were calculated as a measure of agreement between the CAM-ICU and ICDSC.ResultsA total of 595 patients were enrolled in the study. There were 69 (12%) emergency surgical, 207 (35%) elective surgical and 319 (54%) medical patients. Delirium incidence evaluated by the ICDSC, but not by the CAM-ICU, was similar among the three groups. Overall agreement between CAM-ICU and ICDSC was moderate (k = 0.5) to substantial (AC1 = 0.71). In medical patients the agreement between the two instruments was moderate (k = 0.53) to substantial (AC1 = 0.76). The agreement between the two tools in emergency surgical patients was also moderate (k = 0.53) to substantial (AC1 = 0.68). In elective surgical patients the agreement between the two instruments was low (k = 0.42) to substantial (AC1 = 0.74).Agreement rates seemed to be influenced by disease severity. The agreement rate in the general ICU population with APACHE II = ConclusionsThe agreement rates between CAM-ICU and ICDSC may vary between different groups of ICU patients and seems to be affected by disease severity.

Chlamydia trachomatis are obligate intracellular bacteria that survive and replicate in a bacterial-modified phagosome called inclusion. As other intracellular parasites, these bacteria subvert the phagocytic pathway to avoid degradation in phagolysosomes and exploit trafficking pathways to acquire both energy and nutrients essential for their survival. Rabs are host proteins that control intracellular vesicular trafficking. Rab14, a Golgi-related Rab, controls Golgi to endosomes transport. Since Chlamydia establish a close relationship with the Golgi apparatus, the recruitment and participation of Rab14 on inclusion development and bacteria growth were analyzed. Time course analysis revealed that Rab14 associated with inclusions by 10 h post infection and was maintained throughout the entire developmental cycle. The recruitment was bacterial protein synthesis-dependent but independent of microtubules and Golgi integrity. Overexpression of Rab14 dominant negative mutants delayed inclusion enlargement, and impaired bacteria replication as determined by IFU. Silencing of Rab14 by siRNA also decreased bacteria multiplication and infectivity. By electron microscopy, aberrant bacteria were observed in cells overexpressing the cytosolic negative Rab14 mutant. Our results showed that Rab14 facilitates the delivery of sphingolipids required for bacterial development and replication from the Golgi to chlamydial inclusions. Novel anti-chlamydial therapies could be developed based on the knowledge of how bacteria subvert host vesicular transport events through Rabs manipulation.