A multicentre, clinical evaluation of a hydro-responsive wound dressing: the Glasgow experience.

OBJECTIVE: Our aim was to assess the effectiveness of hydro-responsive wound dressing (HRWD) in debridement and wound bed preparation of a variety of acute and chronic wounds that presented with devitalised tissue needing removal so that healing may proceed. METHOD: This was a non-comparative evaluation of acute and chronic wounds that required debridement as part of their normal treatment regimen. Clinicians recorded wound changes including a subjective assessment level of devitalised tissue and wound bed preparation, presence of pain, wound status (e.g., wound size) and periwound skin condition. Data was also collected from clinicians and patients to provide information on clinical performance of the dressing. RESULTS: We recruited 100 patients with a variety of wound types into the study. Over 90% of the clinicians reported removal of devitalised tissue to enable a healing response in both chronic and acute wounds. Specifically, over the course of the evaluation period, levels of devitalised tissue (necrosis and slough) reduced from 85.5% to 26.3%, and this was accompanied by an increase in wound bed granulation from 12.0% to 33.7%. Correspondingly, there was a 40% reduction in wound area, hence a clinically relevant healing response was seen upon treatment with HRWD. It is also noteworthy that this patient population included a significant proportion of chronic wounds (51.4%) that showed no signs of wound progression within <4 weeks before study inclusion. Of these chronic wounds, 93% demonstrated wound progression upon treatment with HRWD. Despite reported pain levels being low pre- and post-dressing change, overall wound pain improved (reduced) in 48% of patients. Periwound skin condition showed a tendency towards improvement, and the fluid management capabilities of the HRWD was reported as good to excellent in the majority of cases. Wound infections were reduced by at least 60% over the evaluation period. A simple cost-effective analysis demonstrated significant savings using HRWD (£6.33) over current standard practice regimens of a four-step debridement process (£8.05), larval therapy (£306.39) and mechanical pad debridement (£11.46). CONCLUSION: HRWD was well tolerated and was demonstrated to be an efficient debridement tool providing rapid, effective and pain free debridement in a variety of wound types.

Benefit of Treating Hepatocellular Carcinoma Recurrence after Liver Transplantation and Analysis of Prognostic Factors for Survival in a Large Euro-American Series.

PURPOSE: To identify prognostic factors after hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). METHODS: We retrospectively reviewed the combined experience at Toronto General Hospital and Hospital Vall d'Hebron managing HCC recurrence after LT (n = 121) between 2000 and 2012. We analyzed prognostic factors by uni- and multi-variate analysis. Median follow-up from LT was 29.5 (range 2-129.4) months. Median follow-up from HCC recurrence was 12.2 (range 0.1-112.5) months. RESULTS: At recurrence, 31.4 % were treated with curative-intent treatments (surgery or ablation), 42.1 % received palliative treatment, and 26.4 % received best supportive care. The 1-, 3-, and 5-year survivals, respectively, after HCC recurrence were 75, 60, and 31 %, vs. 60, 19, and 12 %, vs. 52, 4, and 5 % (p < 0.001). By multivariate analysis, not being amenable to a curative-intent treatment [hazard ratio (HR) 4.7, 95 % confidence interval (CI) 2.7-8.3, p < 0.001], α-fetoprotein of ≥100 ng/mL at the time of HCC recurrence (HR 2.1, 95 % CI 1.3-2.3, p = 0.002) and early recurrence (<12 months) after LT (HR 1.6, 95 % CI 1.1-2.5, p = 0.03) were found to be poor prognosis factors. A prognostic score was devised on the basis of these three independent variables. Patients were divided into three groups, as follows: good prognosis, 0 points (n = 22); moderate prognosis, 1 or 2 points (n = 84); and poor prognosis, 3 points (n = 15). The 1-, 3-, and 5-year actuarial survival for each group was 91, 50, and 50 %, vs. 52, 7, and 2 %, vs. 13, 0, and 0 %, respectively (p < 0.001). CONCLUSIONS: Patients with HCC recurrence after transplant amenable to curative-intent treatments can experience significant long-term survival (~50 % at 5 years), so aggressive management should be offered. Poor prognosis factors after recurrence are not being amenable to a curative-intent treatment, α-fetoprotein of ≥100 ng/mL, and early (<1 year) recurrence after LT.

A survey of some pre-analytical errors identified from the Biochemistry Department of a Scottish hospital.

BACKGROUND: It is estimated that 70% of all health care decisions affecting diagnosis or treatment involve laboratory testing. The pre-analytical phase of the testing process shows the highest prevalence of errors accounting for 70% of all mistakes in laboratory diagnostics. It is recommended that laboratories collect statistics on pre-analytical error rates. This survey examined some mistakes in blood collection, i.e. specimen haemolysis, and EDTA contamination. METHODS: Survey was from June 2011 to May 2012. Haemolysis was detected by analysers' automated haemolysis index function. Plasma EDTA was measured by an automated system. Data were captured from our laboratory information management system. RESULTS: For a total workload of 763,577 blood specimens, the overall haemolysis rate was 3.2%. Much higher rates of both specimen haemolysis and EDTA contamination were observed when blood was not collected by trained phlebotomists. CONCLUSIONS: Better training in blood collection, achieving the standard of professional phlebotomists, will improve validity of diagnostic information; reduce risks of dangerous misinterpretation of results, unwanted anaemia and needlestick injury and decrease laboratory supplies costs. This type of audit could be replicated in other Scottish Health Boards with some benefit and thereby better target future training needs.

Exploring the Hidden Complexity: Entropy Analysis in Pulse Oximetry of Female Athletes.

This study examines the relationship between physiological complexity, as measured by Approximate Entropy (ApEn) and Sample Entropy (SampEn), and fitness levels in female athletes. Our focus is on their association with maximal oxygen consumption (VO2,max). Our findings reveal a complex relationship between entropy metrics and fitness levels, indicating that higher fitness typically, though not invariably, correlates with greater entropy in physiological time series data; however, this is not consistent for all individuals. For Heart Rate (HR), entropy measures suggest stable patterns across fitness categories, while pulse oximetry (SpO2) data shows greater variability. For instance, the medium fitness group displayed an ApEn(HR) = 0.57±0.13 with a coefficient of variation (CV) of 22.17 and ApEn(SpO2) = 0.96±0.49 with a CV of 46.08%, compared to the excellent fitness group with ApEn(HR) = 0.60±0.09 with a CV of 15.19% and ApEn(SpO2) =0.85±0.42 with a CV of 49.46%, suggesting broader physiological responses among more fit individuals. The larger standard deviations and CVs for SpO2 entropy may indicate the body's proficient oxygen utilization at higher levels of physical demand. Our findings advocate for combining entropy metrics with wearable sensor technology for improved biomedical analysis and personalized healthcare.

Combined dysfunctions of immune cells predict nosocomial infection in critically ill patients.

BACKGROUND: Nosocomial infection occurs commonly in intensive care units (ICUs). Although critical illness is associated with immune activation, the prevalence of nosocomial infections suggests concomitant immune suppression. This study examined the temporal occurrence of immune dysfunction across three immune cell types, and their relationship with the development of nosocomial infection. METHODS: A prospective observational cohort study was undertaken in a teaching hospital general ICU. Critically ill patients were recruited and underwent serial examination of immune status, namely percentage regulatory T-cells (Tregs), monocyte deactivation (by expression) and neutrophil dysfunction (by CD88 expression). The occurrence of nosocomial infection was determined using pre-defined, objective criteria. RESULTS: Ninety-six patients were recruited, of whom 95 had data available for analysis. Relative to healthy controls, percentage Tregs were elevated 6-10 days after admission, while monocyte HLA-DR and neutrophil CD88 showed broader depression across time points measured. Thirty-three patients (35%) developed nosocomial infection, and patients developing nosocomial infection showed significantly greater immune dysfunction by the measures used. Tregs and neutrophil dysfunction remained significantly predictive of infection in a Cox hazards model correcting for time effects and clinical confounders {hazard ratio (HR) 2.4 [95% confidence interval (CI) 1.1-5.4] and 6.9 (95% CI 1.6-30), respectively, P=0.001}. Cumulative immune dysfunction resulted in a progressive risk of infection, rising from no cases in patients with no dysfunction to 75% of patients with dysfunction of all three cell types (P=0.0004). CONCLUSIONS: Dysfunctions of T-cells, monocytes, and neutrophils predict acquisition of nosocomial infection, and combine additively to stratify risk of nosocomial infection in the critically ill.

A new dimension for the human genome project: towards comprehensive expression maps.

The current Human Genome Project is largely devoted to structural characterisation of our genome. We now need international co-ordination of a second phase of genome analysis, the systematic construction of expression maps using both basic and high-resolution expression assays. Databases recording different types of expression pattern for a variety of human cell types need to be established and co-ordinated. There is a compelling need for a database of gene expression in early human development, but the scarcity of human material for study requires optimisation of research strategies and co-ordination of expression studies in early human and mouse development.

Lung disease in the cystic fibrosis mouse exposed to bacterial pathogens.

Lung disease is the major cause of death in cystic fibrosis (CF), but there is no evidence for overt lung involvement at birth. We show here that the same is true for the gene targeted cftrm1HGU mutant mouse. Furthermore, this CF mouse model demonstrates an impaired capacity to clear Staphylococcus aureus and Burkholderia (Pseudomonas) cepacia, two opportunistic lung pathogens closely associated with lung disease in CF subjects. The cftrm1HGU homozygotes display mucus retention and frank lung disease in response to repeated microbial exposure. Thus, lung disease in the cftrm1HGU mouse develops in response to bacterial infection, establishing a model to dissect the pathogenesis of CF pulmonary disease and providing a clinically relevant end point to assess the efficacy of pharmacologic or genetic interventions.

The utility of the Sydney Melancholia Prototype Index (SMPI) for predicting response to electroconvulsive therapy in depression: A CARE Network study.

An enhanced understanding of clinical predictors of positive ECT outcome could assist with the decision to prescribe ECT for select patients. Reliable predictors of ECT response such as psychotic symptoms and age have been identified, however, studies of melancholia and ECT response have been inconsistent. The Sydney Melancholia Prototype Index (SMPI) is a clinical measure designed to differentiate melancholic and non-melancholic depression. This study aimed to investigate whether melancholic depression (as measured by the clinician rated version of the SMPI) predicted a better response to ECT than non-melancholic depression. The study included data collated from four participating sites in the Clinical Alliance for ECT and Related treatments (CARE) network. The primary outcome was response (>50% improvement) on the Montgomery Asberg Depression Rating Scale (MADRS) and the secondary outcome was raw change in MADRS score. Of the 329 depressed patients included in the study, 81% had melancholic features and 76% met criteria for clinical response. SMPI defined melancholia was associated with older age, higher pre-treatment mood scores and presence of psychosis. Melancholia as defined by the SMPI, however, did not significantly predict either clinical response or overall mood improvement with ECT in multivariate analyses. Instead, older age, greater pre-treatment depression severity and the use of bifrontal compared to right unilateral ultrabrief ECT were significant predictors of mood improvement. Path analysis showed that higher pre-treatment mood score and older age were independently associated with mood improvement with ECT.

Factors related to human-vector contact that modify the likelihood of malaria transmission during a contained Plasmodium falciparum outbreak in Praia, Cabo Verde.

Background: Determining the reproductive rate and how it varies over time and space (RT) provides important insight to understand transmission of a given disease and inform optimal strategies for controlling or eliminating it. Estimating RT for malaria is difficult partly due to the widespread use of interventions and immunity to disease masking incident infections. A malaria outbreak in Praia, Cabo Verde in 2017 provided a unique opportunity to estimate RT directly, providing a proxy for the intensity of vector-human contact and measure the impact of vector control measures. Methods: Out of 442 confirmed malaria cases reported in 2017 in Praia, 321 (73%) were geolocated and informed this analysis. RT was calculated using the joint likelihood of transmission between two cases, based on the time (serial interval) and physical distance (spatial interval) between them. Log-linear regression was used to estimate factors associated with changes in RT, including the impact of vector control interventions. A geostatistical model was developed to highlight areas receptive to transmission where vector control activities could be focused in future to prevent or interrupt transmission. Results: The RT from individual cases ranged between 0 and 11 with a median serial- and spatial-interval of 34 days [interquartile range (IQR): 17-52] and 1,347 m (IQR: 832-1,985 m), respectively. The number of households receiving indoor residual spraying (IRS) 4 weeks prior was associated with a reduction in RT by 0.84 [95% confidence interval (CI) 0.80-0.89; p-value <0.001] in the peak-and post-epidemic compared to the pre-epidemic period. Conclusions: Identifying the effect of reduced human-vector contact through IRS is essential to determining optimal intervention strategies that modify the likelihood of malaria transmission and can inform optimal intervention strategies to accelerate time to elimination. The distance within which two cases are plausibly linked is important for the potential scale of any reactive interventions as well as classifying infections as imported or introduced and confirming malaria elimination.

The utility of the brief ECT cognitive screen (BECS) for early prediction of cognitive adverse effects from ECT: A CARE network study.

Although highly effective, electroconvulsive therapy (ECT) often produces cognitive side effects which can be a barrier for patients. Monitoring cognitive side effects during the acute course is therefore recommended to identify patients at increased risk for adverse outcomes. The Brief ECT Cognitive Screen (BECS) is a brief instrument designed to measure emerging cognitive side effects from ECT. The aim of this study was to examine the clinical utility of the BECS for predicting adverse cognitive outcomes in real world clinic settings. The study included data collated from four participating sites in the Clinical Alliance for ECT and Related treatments (CARE) network. The BECS was administered at pre ECT and post 3 or 4 ECT. The primary outcome was a ≥4 point decrease on the Montreal Cognitive Assessment (MoCA) from pretreatment to post ECT. Logistic multiple regression analyses examined the BECS and other relevant clinical and demographic and treatment factors as predictors. The final analysis included 623 patients with diverse indications for ECT including 53.6% with major depression and 33.7% with schizophrenia or schizoaffective disorder. A higher total score on the BECS significantly predicted decline in Total Scores on the MoCA [B = 0.25 (0.08), p = 0.003], though not decline in MoCA Delayed Recall scores (p > 0.1). Other significant predictors included higher pretreatment MoCA Total Scores and female gender for verbal anterograde memory decline. This study confirmed that the BECS has clinical utility for identifying patients with both reduced and increased risk for adverse cognitive outcomes from ECT.

Association of tyrosine protein kinase Zap-70 with the protooncogene product p120c-cbl in T lymphocytes.

Accumulating data show that the tyrosine protein kinase Zap-70 plays an essential role in T cell receptor-mediated signal transduction. However, the model of action, as well as the physiologically relevant substrates of Zap-70, have not been determined. We have attempted to identify a 120-kD tyrosine-phosphorylated protein (p120) that associates with Zap-70 in activated T lymphocytes. The results of our analyses showed that p120 is largely encoded by the c-cbl protooncogene. Furthermore, the association of Zap-70 with c-Cbl was shown to be induced by T cell receptor stimulation, implying that it required posttranslational modification of one or both of these products. FynT, but not Lck, also associated with c-Cbl in activated T cells. Finally, using a heterologous system, it was demonstrated that the ability of Zap-70 to cause tyrosine phosphorylation of p120c-cbl was dependent on Lck- or FynT-mediated signals. As c-Cbl can associate with several other signaling molecules, it may couple Zap-70 to downstream effectors during T cell activation.

Differential regulation of T cell antigen responsiveness by isoforms of the src-related tyrosine protein kinase p59fyn.

Recent observations suggest that the src-related tyrosine protein kinase p59fyn may be involved in antigen-induced T lymphocyte activation. As a result of alternative splicing, p59fyn exists as two isoforms that differ exclusively within a short sequence spanning the end of the Src Homology 2 (SH2) region and the beginning of the tyrosine protein kinase domain. While one p59fyn isoform (fynB) is highly expressed in brain, the alternative product (fynT) is principally found in T lymphocytes. To further understand the role of p59fyn in T cell activation and to test the hypothesis that p59fynT serves a tissue-specific function in T lymphocytes, we have examined the effects of expression of activated versions (tyrosine 528 to phenylalanine 528 mutants) of either form of p59fyn on the physiology of an antigen-specific mouse T cell hybridoma. Our results demonstrated that the two forms of fyn, expressed in equivalent amounts, efficiently enhanced antibody-induced T cell receptor (TCR)-mediated signals. In contrast, only p59fynT increased interleukin 2 production in response to antigen stimulation. This finding implies that the distinct p59fyn isoform expressed in T lymphocytes regulates the coupling of TCR stimulation by antigen/major histocompatibility complex to lymphokine production.

Clnk, a novel SLP-76-related adaptor molecule expressed in cytokine-stimulated hemopoietic cells.

We have identified a novel Src homology 2 domain-containing leukocyte protein of 76 kD (SLP-76)-related molecule which we have termed Clnk (for cytokine-dependent hemopoietic cell linker). Unlike its relatives SLP-76 and B cell linker protein (Blnk), Clnk is not expressed uniformly within a given hemopoietic cell lineage. Even though it can be detected in several cell types, including T cells, natural killer cells, and mast cells, its expression seems to be strictly dependent on sustained exposure to cytokines such as interleukin (IL)-2 and IL-3. Strong support for the notion that Clnk is involved in immunoreceptor signaling was provided by the observation that it inducibly associated with at least one tyrosine-phosphorylated polypeptide (p92) in response to immunoreceptor stimulation. Moreover, transient expression of Clnk caused an increase in immunoreceptor-mediated signaling events in a T cell line. Taken together, these results show that Clnk is a novel member of the SLP-76 family selectively expressed in cytokine-stimulated hemopoietic cells. Furthermore, they suggest that Clnk may be involved in a cross-talk mechanism between cytokine receptor and immunoreceptor signaling.

5-Aminouracil treatment. A method for estimating G2.

Treatment of Vicia faba lateral roots with a range of concentrations of 5-aminouracil (5-AU) indicate that cells are stopped at a particular point in interphase. The timing of the fall in mitotic index suggests that cells are held at the S - G(2) transition. When cells are held at this point, treatments with 5-AU can be used to estimate the duration of G(2) + mitosis/2 of proliferating cells. Treatment with 5-AU can also be used to demonstrate the presence of subpopulations of dividing cells that differ in their G(2) duration. Using this method, 5-AU-induced inhibition, we have confirmed that in V. faba lateral roots there are two populations of dividing cells: (a) a fast-dividing population, which makes up approximately 85% of the proliferating cell population and has a G(2) + mitosis/2 duration of 3.3 hr, and (b) a slow-dividing population, which makes up approximately 15% of dividing cells and has a G(2) duration in excess of 12 hr. These estimates are similar to those obtained from percentage labeled mitosis (PLM) curves after incorporation of thymidine-(3)H.

Evidence from thymidine-3H-labeled meristems of Vicia faba of two cell populations.

Treatments with tritiated thymidine (TdR-(3)H) have revealed the existence of two populations of mitotically active cells in meristems of lateral roots of Vicia faba. A rapidly dividing population, with a cycle time of 14 hr, constitutes about half the cells in the meristem. A second population of cells, with a cycle time in excess of 30 hr, is also present. Estimates of the relative size of this slowly dividing population are more difficult to make, but we calculate that this population includes 27-43% of meristem cells. The remaining fraction of the meristem is made up of cells that divide rarely or not at all. Since, at all times, both populations contribute to the mitotic index, the curve of the percentage of labeled mitoses that can be determined after a pulse label with TdR-(3)H differs from the curve expected of an ideal population in an important way: the peak value of the curve of the percentage of labeled mitoses is always less than 100%, usually between 75 and 80%. This heterogeneity within a meristem must be borne in mind in terms of the response of meristems to disruptive treatments, the mechanisms controlling mitotic cycle duration, and the spatial organization of a heterogeneous population in an organ that shows polarized growth.

Competition between seed-eating rodents and ants in desert ecosystems.

Three kinds of evidence indicate that desert rodents and ants compete for seeds: (i) extensive overlaps in diet, (ii) reciprocal increases when one taxon is experimentally excluded, and (iii) complementay patterns of diversity and biomass in georadients of productivity. The effect on seed resources and annual plan geoseems to be similar whether rodents, ants, or both are foraging.

Competition for dispersal in ant-dispersed plants.

Two closely related and coexisting plants (Chenopodiaceae) of the Australian arid zone are adapted for seed dispersal by ants. These facultatively perennial shrubs persist in saltbush communities largely as a result of highly directional dispersal to ant mounds, where conditions are favorable for establishment and growth. The two species grow predominantly on mounds and compete for dispersal to these favorable microhabitats.

Reversal of chloroquine resistance in malaria parasite Plasmodium falciparum by desipramine.

Desipramine and several other tricyclic antidepressant drugs reverse chloroquine resistance in Plasmodium falciparum in vitro at concentrations observed in the plasma of human patients treated for depression. Reversal of resistance is associated with increased chloroquine accumulation in the parasite, probably because of inhibition of a putative chloroquine efflux pump. When owl monkeys (Aotus lemurinus lemurinus) infected with chloroquine-resistant Plasmodium falciparum were treated with chloroquine plus desipramine, their parasitemias were rapidly suppressed. Desipramine was found to be one of the most effective compounds yet described for the reversal of chloroquine resistance both in vitro and in vivo.

Reliability of urine collection pads for routine and metabolic biochemistry in infants and young children.

The aim of our study was to evaluate whether specifically designed urine collection pads give reliable results for routine and metabolic biochemistry tests in paediatric urine. Urine collected by bag or clean-catch from infants and children <2 yrs without metabolic disorders was divided into two aliquots, one of which was added to a collection pad, incubated for 15 min at 37 degrees C (simulating in vivo collection conditions), then recovered by aspiration. Urine from adults with phaeochromocytoma and aqueous solutions of catecholamines were similarly treated. Routine, catecholamine, and metabolic analyses were performed on pad/non-pad aliquots. Selected metabolic analyses were also performed on pad/non-pad urine from patients with diagnosed inborn errors and urine containing added metabolites to simulate metabolic disorders. Routine tests (urea, electrolytes, creatinine, osmolality, calcium:creatinine, phosphate:creatinine, magnesium:creatinine, urate:creatinine [n = 32], oxalate:creatinine [n = 10]), and catecholamines (n = 12) showed good or acceptable concordance with no clinically significant pad/non-pad differences. Metabolic tests in infants and children without metabolic disorders all showed good pad/non-pad concordance for amino acids (n = 10), organic acids (n = 12), and glycosaminoglycans (n = 8). In patients with metabolic disorders (phenylketonuria [n = 1], homozygous/heterozygous cystinuria [n = 3], mucopolysaccharidoses II [n = 2] and III [n = 1], organic acid disorders [n = 6]) and urine containing added orotic acid to simulate urea cycle disorders, there was also good pad/non-pad concordance for diagnostic urinary metabolites. No extraneous organic acids were eluted from the pads. Sugar chromatography showed identical staining intensity in pad/non-pad samples. In conclusion, urine collection pads give reliable results for a wide range of routine and metabolic biochemistry tests in urine from paediatric patients.