The 28-day mortality prediction in sepsis patients using static lactate concentration and early lactate clearance: an observational study.

Sepsis causes high mortality and morbidity. Static lactate concentration and early lactate clearance are cited to be a predictor for sepsis survival. This study examined the clinical utility of static lactate concentration and early lactate clearance within the first six hours of admission in Emergency Department (ED) to predict 28-day mortality rate in sepsis patients. Patients who presented with sepsis, severe sepsis or septic shock and admitted to ED of Universiti Kebangsaan Malaysia Medical Centre were recruited. Blood lactate concentrations were measured upon admission (H0), at 1st hour (H1) and 6th hour (H6), respectively. Either standard treatment of sepsis or early goal directed therapy was initiated according to sepsis severity. A follow-up report was conducted at 28 days via telephone call, e-mail or case notes. Patients were later classified into survivor and non-survivor as final outcome. Static lactate concentration appeared to be significantly higher for non-survivor as compared to the survival group at H0, H1 and H6 (p<0.05). The lactate clearance trend reflects no relationship between early lactate clearance and 28-day mortality. Static lactate concentration showed a superior predictor for sepsis over early lactate clearance. Although early lactate clearance was unable to prove its ability to predict 28-day mortality, our findings suggest it can be a useful tool to gauge the resuscitation outcome

Marine Scientific Research in the South China Sea

The research project aims to identify options for multilateral marine science research (MSR) mechanisms in South China Sea that could be piloted and discussed with ASEAN partners. The project will enable the UK to expand engagement with ASEAN as a partner of choice for expertise on maritime issues

A rapid high-performance semi-automated tool to measure total kidney volume from MRI in autosomal dominant polycystic kidney disease.

OBJECTIVES: To develop a high-performance, rapid semi-automated method (Sheffield TKV Tool) for measuring total kidney volume (TKV) from magnetic resonance images (MRI) in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS: TKV was initially measured in 61 patients with ADPKD using the Sheffield TKV Tool and its performance compared to manual segmentation and other published methods (ellipsoidal, mid-slice, MIROS). It was then validated using an external dataset of MRI scans from 65 patients with ADPKD. RESULTS: Sixty-one patients (mean age 45 ± 14 years, baseline eGFR 76 ± 32 ml/min/1.73 m2) with ADPKD had a wide range of TKV (258-3680 ml) measured manually. The Sheffield TKV Tool was highly accurate (mean volume error 0.5 ± 5.3% for right kidney, - 0.7 ± 5.5% for left kidney), reproducible (intra-operator variability - 0.2 ± 1.3%; inter-operator variability 1.1 ± 2.9%) and outperformed published methods. It took less than 6 min to execute and performed consistently with high accuracy in an external MRI dataset of T2-weighted sequences with TKV acquired using three different scanners and measured using a different segmentation methodology (mean volume error was 3.45 ± 3.96%, n = 65). CONCLUSIONS: The Sheffield TKV Tool is operator friendly, requiring minimal user interaction to rapidly, accurately and reproducibly measure TKV in this, the largest reported unselected European patient cohort with ADPKD. It is more accurate than estimating equations and its accuracy is maintained at larger kidney volumes than previously reported with other semi-automated methods. It is free to use, can run as an independent executable and will accelerate the application of TKV as a prognostic biomarker for ADPKD into clinical practice. KEY POINTS: • This new semi-automated method (Sheffield TKV Tool) to measure total kidney volume (TKV) will facilitate the routine clinical assessment of patients with ADPKD. • Measuring TKV manually is time consuming and laborious. • TKV is a prognostic indicator in ADPKD and the only imaging biomarker approved by the FDA and EMA

Family doctors' involvement with families in Estonia

BACKGROUND: Family doctors should care for individuals in the context of their family. Family has a powerful influence on health and illness and family interventions have been shown to improve health outcomes for a variety of health problems. The aim of the study was to investigate the Estonian family doctors' (FD) attitudes to the patients' family-related issues in their work: to explore the degree of FDs involvement in family matters, their preparedness for management of family-related issues and their self-assessment of the ability to manage different family-related problems. METHODS: A random sample (n = 236) of all FDs in Estonia was investigated using a postal questionnaire. Altogether 151 FDs responded to the questionnaire (response rate 64%), while five of them were excluded as they did not actually work as FDs. RESULTS: Of the respondents, 90% thought that in managing the health problems of patients FDs should communicate and cooperate with family members. Although most of the family doctors agreed that modifying of the health damaging risk factors (smoking, alcohol and drug abuse) of their patients and families is their task, one third of them felt that dealing with these problems is ineffective, or perceived themselves as poorly prepared or having too little time for such activities. Of the respondents, 58% (n = 83) were of the opinion that they could modify also relationship problems. CONCLUSIONS: Estonian family doctors are favourably disposed to involvement in family-related problems, however, they need some additional training, especially in the field of relationship management

Determining Possible Shared Genetic Architecture Between Myopia and Primary Open-Angle Glaucoma

PURPOSE: To determine genetic correlations between common myopia and primary open-angle glaucoma (POAG). // METHODS: We tested the association of myopia polygenic risk scores (PRSs) with POAG and POAG endophenotypes using two studies: the Australian & New Zealand Registry of Advanced Glaucoma (ANZRAG) study comprising 798 POAG cases with 1992 controls, and the Rotterdam Study (RS), a population-based study with 11,097 participants, in which intraocular pressure (IOP) and optic disc parameter measurements were catalogued. PRSs were derived from genome-wide association study meta-analyses conducted by the Consortium for Refractive Error and Myopia (CREAM) and 23andMe. In total, 12 PRSs were constructed and tested. Further, we explored the genetic correlation between myopia, POAG, and POAG endophenotypes by using the linkage disequilibrium score regression (LDSC) method. // RESULTS: We did not find significant evidence for an association between PRS of myopia with POAG (P = 0.81), IOP (P = 0.07), vertical cup-disc ratio (P = 0.42), or cup area (P = 0.25). We observed a nominal association with retinal nerve fiber layer (P = 7.7 × 10-3) and a significant association between PRS for myopia and disc area (P = 1.59 × 10-9). Using the LDSC method, we found a genetic correlation only between myopia and disc area (genetic correlation [RhoG] = -0.12, P = 1.8 × 10-3), supporting the findings of the PRS approach. // CONCLUSIONS: Using two complementary approaches we found no evidence to support a genetic overlap between myopia and POAG; our results suggest that the comorbidity of these diseases is not influenced by common variants. The association between myopia and optic disc size is well known and validates this methodology

Inhibition of the tyrosine phosphatase SHP-2 suppresses angiogenesis in vitro and in vivo

Endothelial cell survival is indispensable to maintain endothelial integrity and initiate new vessel formation. We investigated the role of SHP-2 in endothelial cell survival and angiogenesis in vitro as well as in vivo. SHP-2 function in cultured human umbilical vein and human dermal microvascular endothelial cells was inhibited by either silencing the protein expression with antisense-oligodesoxynucleotides or treatment with a pharmacological inhibitor (PtpI IV). SHP-2 inhibition impaired capillary-like structure formation (p < 0.01; n = 8) in vitro as well as new vessel growth ex vivo (p < 0.05; n = 10) and in vivo in the chicken chorioallantoic membrane (p < 0.01, n = 4). Additionally, SHP-2 knock-down abrogated fibroblast growth factor 2 (FGF-2)-dependent endothelial proliferation measured by MTT reduction ( p ! 0.01; n = 12). The inhibitory effect of SHP-2 knock-down on vessel growth was mediated by increased endothelial apoptosis ( annexin V staining, p ! 0.05, n = 9), which was associated with reduced FGF-2-induced phosphorylation of phosphatidylinositol 3-kinase (PI3-K), Akt and extracellular regulated kinase 1/2 (ERK1/2) and involved diminished ERK1/2 phosphorylation after PI3-K inhibition (n=3). These results suggest that SHP-2 regulates endothelial cell survival through PI3-K-Akt and mitogen-activated protein kinase pathways thereby strongly affecting new vessel formation. Thus, SHP-2 exhibits a pivotal role in angiogenesis and may represent an interesting target for therapeutic approaches controlling vessel growth. Copyright (C) 2007 S. Karger AG, Basel

A Cross-Sectional Study of People with Epilepsy and Neurocysticercosis in Tanzania: Clinical Characteristics and Diagnostic Approaches.

Neurocysticercosis (NCC) is a major cause of epilepsy in regions where pigs are free-ranging and hygiene is poor. Pork production is expected to increase in the next decade in sub-Saharan Africa, hence NCC will likely become more prevalent. In this study, people with epilepsy (PWE, n=212) were followed up 28.6 months after diagnosis of epilepsy. CT scans were performed, and serum and cerebrospinal fluid (CSF) of selected PWE were analysed. We compared the demographic data, clinical characteristics, and associated risk factors of PWE with and without NCC. PWE with NCC (n=35) were more likely to be older at first seizure (24.3 vs. 16.3 years, p=0.097), consumed more pork (97.1% vs. 73.6%, p=0.001), and were more often a member of the Iraqw tribe (94.3% vs. 67.8%, p=0.005) than PWE without NCC (n=177). PWE and NCC who were compliant with anti-epileptic medications had a significantly higher reduction of seizures (98.6% vs. 89.2%, p=0.046). Other characteristics such as gender, seizure frequency, compliance, past medical history, close contact with pigs, use of latrines and family history of seizures did not differ significantly between the two groups. The number of NCC lesions and active NCC lesions were significantly associated with a positive antibody result. The electroimmunotransfer blot, developed by the Centers for Disease Control and Prevention, was more sensitive than a commercial western blot, especially in PWE and cerebral calcifications. This is the first study to systematically compare the clinical characteristics of PWE due to NCC or other causes and to explore the utility of two different antibody tests for diagnosis of NCC in sub-Saharan Africa

Introducing a new breed of wine yeast: interspecific hybridisation between a commercial Saccharomyces cerevisiae wine yeast and Saccharomyces mikatae

Interspecific hybrids are commonplace in agriculture and horticulture; bread wheat and grapefruit are but two examples. The benefits derived from interspecific hybridisation include the potential of generating advantageous transgressive phenotypes. This paper describes the generation of a new breed of wine yeast by interspecific hybridisation between a commercial Saccharomyces cerevisiae wine yeast strain and Saccharomyces mikatae, a species hitherto not associated with industrial fermentation environs. While commercially available wine yeast strains provide consistent and reliable fermentations, wines produced using single inocula are thought to lack the sensory complexity and rounded palate structure obtained from spontaneous fermentations. In contrast, interspecific yeast hybrids have the potential to deliver increased complexity to wine sensory properties and alternative wine styles through the formation of novel, and wider ranging, yeast volatile fermentation metabolite profiles, whilst maintaining the robustness of the wine yeast parent. Screening of newly generated hybrids from a cross between a S. cerevisiae wine yeast and S. mikatae (closely-related but ecologically distant members of the Saccharomyces sensu stricto clade), has identified progeny with robust fermentation properties and winemaking potential. Chemical analysis showed that, relative to the S. cerevisiae wine yeast parent, hybrids produced wines with different concentrations of volatile metabolites that are known to contribute to wine flavour and aroma, including flavour compounds associated with non-Saccharomyces species. The new S. cerevisiae x S. mikatae hybrids have the potential to produce complex wines akin to products of spontaneous fermentation while giving winemakers the safeguard of an inoculated ferment.Jennifer R. Bellon, Frank Schmid, Dimitra L. Capone, Barbara L. Dunn, Paul J. Chamber

Early clinical and laboratory risk factors of intensive care unit requirement during 2004–2008 dengue epidemics in Singapore: a matched case–control study

Background: Dengue infection can result in severe clinical manifestations requiring intensive care. Effective triage is critical for early clinical management to reduce morbidity and mortality. However, there is limited knowledge on early risk factors of intensive care unit (ICU) requirement. This study aims to identify early clinical and laboratory risk factors of ICU requirement at first presentation in hospital and 24 hours prior to ICU requirement. Method: A retrospective 1:4 matched case–control study was performed with 27 dengue patients who required ICU, and 108 dengue patients who did not require ICU from year 2004–2008, matched by year of dengue presentation. Univariate and multivariate conditional logistic regression were performed. Optimal predictive models were generated with statistically significant risk factors identified using stepwise forward and backward elimination method. Results: ICU dengue patients were significantly older (P=0.003) and had diabetes (P=0.031), compared with non-ICU dengue patients. There were seven deaths among ICU patients at median seven days post fever. At first presentation, the WHO 2009 classification of dengue severity was significantly associated (P<0.001) with ICU, but not the WHO 1997 classification. Early clinical risk factors at presentation associated with ICU requirement were hematocrit change ≥20% concurrent with platelet <50 K [95% confidence-interval (CI)=2.46-30.53], hypoproteinemia (95% CI=1.09-19.74), hypotension (95% CI=1.83-31.79) and severe organ involvement (95% CI=3.30-331). Early laboratory risk factors at presentation were neutrophil proportion (95% CI=1.04-1.17), serum urea (95% CI=1.02-1.56) and alanine aminotransferase level (95% CI=1.001-1.06). This predictive model has sensitivity and specificity up to 88%. Early laboratory risk factors at 24 hours prior to ICU were lymphocyte (95% CI=1.03-1.38) and monocyte proportions (95% CI=1.02-1.78), pulse rate (95% CI=1.002-1.14) and blood pressure (95% CI=0.92-0.996). This predictive model has sensitivity and specificity up to 88.9% and 78%, respectively. Conclusions: This is the first matched case–control study, to our best knowledge, that identified early clinical and laboratory risk factors of ICU requirement during hospitalization. These factors suggested differential pathophysiological background of dengue patients as early as first presentation prior to ICU requirement, which may reflect the pathogenesis of dengue severity. These risk models may facilitate clinicians in triage of patients, after validating in larger independent studies.Published versio

Full Mouth Rehabilitation with Implant-Supported Prostheses for Severe Periodontitis: A Case Report

Oral rehabilitation for a patient with severe loss of alveolar bone and soft tissue resulting from severe periodontitis presents a challenge to clinicians. Replacing loosening natural teeth with fixed prostheses supported by dental implants often requires either gingival surgery or bone grafting. The outcome of the bone grafting is sometimes unpredictable and requires longer healing time and/ or multiple surgeries. The presence of periodontal inflammation and periapical lesions often delay the placement of bone grafts as well as dental implants. Here we present a clinical case of a patient undergone full mouth reconstruction with implant-supported fixed prostheses. We demonstrated that early placement of implants (three weeks after extractions) with minimal bone grafting may be an alternative to conventional bone grafting followed by implant placement. We believe that primary stability during implant placement may contribute to our success. In addition, composite resin gingival material may be indicated in cases of large fixed implant prostheses as an alternative to pink porcelain