Development of a logic regression-based approach for the discovery of host- and niche-informative biomarkers in Escherichia coli and their application for microbial source tracking.

Microbial source tracking leverages a wide range of approaches designed to trace the origins of fecal contamination in aquatic environments. Although source tracking methods are typically employed within the laboratory setting, computational techniques can be leveraged to advance microbial source tracking methodology. Herein, we present a logic regression-based supervised learning approach for the discovery of source-informative genetic markers within intergenic regions across the Escherichia coli genome that can be used for source tracking. With just single intergenic loci, logic regression was able to identify highly source-specific (i.e., exceeding 97.00%) biomarkers for a wide range of host and niche sources, with sensitivities reaching as high as 30.00%-50.00% for certain source categories, including pig, sheep, mouse, and wastewater, depending on the specific intergenic locus analyzed. Restricting the source range to reflect the most prominent zoonotic sources of E. coli transmission (i.e., bovine, chicken, human, and pig) allowed for the generation of informative biomarkers for all host categories, with specificities of at least 90.00% and sensitivities between 12.50% and 70.00%, using the sequence data from key intergenic regions, including emrKY-evgAS, ibsB-(mdtABCD-baeSR), ompC-rcsDB, and yedS-yedR, that appear to be involved in antibiotic resistance. Remarkably, we were able to use this approach to classify 48 out of 113 river water E. coli isolates collected in Northwestern Sweden as either beaver, human, or reindeer in origin with a high degree of consensus-thus highlighting the potential of logic regression modeling as a novel approach for augmenting current source tracking efforts.IMPORTANCEThe presence of microbial contaminants, particularly from fecal sources, within water poses a serious risk to public health. The health and economic burden of waterborne pathogens can be substantial-as such, the ability to detect and identify the sources of fecal contamination in environmental waters is crucial for the control of waterborne diseases. This can be accomplished through microbial source tracking, which involves the use of various laboratory techniques to trace the origins of microbial pollution in the environment. Building on current source tracking methodology, we describe a novel workflow that uses logic regression, a supervised machine learning method, to discover genetic markers in Escherichia coli, a common fecal indicator bacterium, that can be used for source tracking efforts. Importantly, our research provides an example of how the rise in prominence of machine learning algorithms can be applied to improve upon current microbial source tracking methodology.

The influence of gender and temephos exposure on community participation in dengue prevention: a compartmental mathematical model.

BACKGROUND: The use of temephos, the most common intervention for the chemical control of Aedes aegypti over the last half century, has disappointing results in control of the infection. The footprint of Aedes and the diseases it carries have spread relentlessly despite massive volumes of temephos. Recent advances in community participation show this might be more effective and sustainable for the control of the dengue vector. METHODS: Using data from the Camino Verde cluster randomized controlled trial, a compartmental mathematical model examines the dynamics of dengue infection with different levels of community participation, taking account of gender of respondent and exposure to temephos. RESULTS: Simulation of dengue endemicity showed community participation affected the basic reproductive number of infected people. The greatest short-term effect, in terms of people infected with the virus, was the combination of temephos intervention and community participation. There was no evidence of a protective effect of temephos 220 days after the onset of the spread of dengue. CONCLUSIONS: Male responses about community participation did not significantly affect modelled numbers of infected people and infectious mosquitoes. Our model suggests that, in the long term, community participation alone may have the best results. Adding temephos to community participation does not improve the effect of community participation alone.

Characteristics of registered research in peritoneal dialysis: Past and present.

Recent national policy changes in the United States and the continued growth of peritoneal dialysis (PD) as a therapy for end-stage kidney disease has renewed interest in this modality. The objective of this study was to describe the current landscape of PD clinical trials to assess trends and gaps in clinical research. An advanced search was completed through ClinicalTrials.gov, yielding 248 studies. Descriptive statistics and Fisher exact tests were used for statistical analysis. Most studies were completed (197, 79.4%), did not indicate a phase (143, 57.7%), were academically sponsored (156, 62.9%), or conducted in Asia (88, 35.5%). There has been overall growth in PD clinical trials since 1995. The type of phase was related to study location (p = 0.008). The type of study intervention was related to study recruitment status, sponsor type, and primary outcome (p = 0.030, p < 0.001, p < 0.001, respectively). Despite growth in PD research worldwide, more studies are being conducted outside the U.S., and static investment in U.S. government-sponsored PD research risks not achieving the goal of increasing availability of home dialysis.

Patient-specific 3D printing to replace components of a rib-to pelvis "Eiffel Tower" vertebral expanding prosthetic titanium rib system in an infant: a case report.

PURPOSE: To address the anatomical challenges facing complex and revision spinal surgery, patient-specific 3D-printed models (3D-PMs) have received growing attention worldwide, primarily in adults. We report the use of a 3D-PM in the treatment of a case of wound breakdown over a component of a VEPTR (Vertical Expandable Prosthetic Titanium Rib; DePuy-Synthes) system, requiring replacement of Dunn-McCarthy hook and sleeve with components contoured to a patient-specific 3D-PM of the spine. METHOD: A two-year-old born with myelomeningocele (MMC), repaired at birth, developed progressive MMC-associated kyphoscoliosis. Elective insertion of a rib-to-pelvis 'Eiffel Tower' bilateral VEPTR growing rods construct was performed without initial complication. Prominence of the right VEPTR sleeve and Dunn-McCarthy hook side-to-side connector resulted in breakdown of overlying poor-quality soft tissues, necessitating washout, partial implant removal, intravenous antibiotic therapy and delayed primary wound closure. A patient-specific 3D-PM, utilising pre-operative CT spine and pelvis 3D-reconstructions, allowed pre-operative formation of a contoured implant, which was inserted without need for further revision. RESULTS: The patient underwent further VEPTR lengthening without recurrent infection, wound breakdown or implant failure at 24-month follow-up. Satisfactory control of the deformity has been achieved with continued improvement in sitting height and radiographic indices. CONCLUSION: This case illustrates the possibility, in certain cases, of using 3D-PM to develop complex components of spinal implant systems pre-operatively, removing the time and difficulty of intra-operative contouring. Consequently, custom-contoured implants may be produced, sterilised and implanted. This technique may be an option, in infants, including MMC-associated kyphoscoliosis, where midline fixation is not possible.

DAPSA, carotid plaque and cardiovascular events in psoriatic arthritis: a longitudinal study.

OBJECTIVE: To examine whether Disease Activity in Psoriatic Arthritis (DAPSA) reflecting the inflammatory component of psoriatic arthritis (PsA) can predict cardiovascular (CV) events independent of traditional CV risk factors and subclinical carotid atherosclerosis. METHODS: A cohort analysis was performed in patients with PsA who had been followed since 2006. The outcome of interest was first CV event. Four different CV disease (CVD) risk scores and DAPSA were computed at baseline. The presence of carotid plaque (CP) and carotid intima-media thickness (CIMT) was also determined in a subgroup of patients using high-resolution ultrasound. The association between DAPSA, CVD risk scores, CP, CIMT and the occurrence of CV events was assessed using Cox proportional hazard models. RESULTS: 189 patients with PsA (mean age: 48.9 years; male: 104 (55.0%)) were recruited. After a median follow-up of 9.9 years, 27 (14.3%) patients developed a CV event. Higher DAPSA was significantly associated with an increased risk of developing CV events (HR: 1.04, 95% CI (1.01 to 1.08), p=0.009). The association remained significant after adjusting for all CV risk scores in the multivariable models. In the subgroup analysis, 154 patients underwent carotid ultrasound assessment and 23 (14.9%) of them experienced a CV event. CP was associated with increased risk of developing CV events after adjusting for three CV risk scores and DAPSA, with HR ranging from 2.35 to 3.42. CONCLUSION: Higher DAPSA and the presence of CP could independently predict CVD events in addition to traditional CV risk scores in patients with PsA.

Treat to target and prevention of subclinical atherosclerosis in psoriatic arthritis-which target should we choose?

OBJECTIVE: PsA patients who achieved sustained minimal disease activity (sMDA) had less subclinical atherosclerosis progression. The vascular effects of achieving other potential treatment targets, including the PsA Disease Activity Score (PASDAS) and the Disease Activity in PsA (DAPSA) score, remained uncertain. This study aimed to compare the vascular effects of achieving different treatment targets in PsA patients. METHOD: This is a post hoc analysis of a 2 year treat-to-target study aimed at MDA. A total of 101 consecutive PsA patients without overt cardiovascular disease were recruited. High-resolution carotid ultrasound and arterial stiffness markers were assessed annually. Low disease activity (LDA) was defined as MDA, DAPSA ≤14 or PASDAS ≤3.2. Sustained disease control was defined as achieving these targets at each visit from month 12 until month 24. RESULTS: Ninety patients [52 male (57.8%), age 50 years (s.d. 11)] who completed 24 months of follow-up were included in this analysis. A total of 44%, 48% and 45% of patients achieved sustained DAPSA LDA (sDAPDA-LDA), sustained PASDAS LDA (sPASDAS-LDA) and sMDA, respectively. Patients who achieved sMDA had significantly less progression of carotid intima-media thickness than those who did not (P = 0.031). Using multivariate analysis, achieving sMDA and sPASDAS-LDA had a protective effect on plaque progression, less increase in total plaque area, reduced mean intima-media thickness and reduced augmentation index after adjusting for covariates. In contrast, no significant differences in the progression of vascular parameters were demonstrated between patients who did or did not achieve sDAPSA-LDA. CONCLUSION: Achieving sMDA/sDASPAS-LDA, but not sDAPSA-LDA, was associated with a protective effect in subclinical atherosclerosis and arterial stiffness progression. A multidimensional domain of disease control might be better in minimizing cardiovascular risk in PsA.

Electrical Stimulation of pediatric cardiac-derived c-kit+ progenitor cells improves retention and cardiac function in right ventricular heart failure.

Nearly 1 in every 120 children born has a congenital heart defect. Although surgical therapy has improved survival, many of these children go on to develop right ventricular heart failure (RVHF). The emergence of cardiovascular regenerative medicine as a potential therapeutic strategy for pediatric HF has provided new avenues for treatment with a focus on repairing or regenerating the diseased myocardium to restore cardiac function. Although primarily tried using adult cells and adult disease models, stem cell therapy is relatively untested in the pediatric population. Here, we investigate the ability of electrical stimulation (ES) to enhance the retention and therapeutic function of pediatric cardiac-derived c-kit+ progenitor cells (CPCs) in an animal model of RVHF. Human CPCs isolated from pediatric patients were exposed to chronic ES and implanted into the RV myocardium of rats. Cardiac function and cellular retention analysis showed electrically stimulated CPCs (ES-CPCs) were retained in the heart at a significantly higher level and longer time than control CPCs and also significantly improved right ventricular functional parameters. ES also induced upregulation of extracellular matrix and adhesion genes and increased in vitro survival and adhesion of cells. Specifically, upregulation of ß1 and ß5 integrins contributed to the increased retention of ES-CPCs. Lastly, we show that ES induces CPCs to release higher levels of pro-reparative factors in vitro. These findings suggest that ES can be used to increase the retention, survival, and therapeutic effect of human c-kit+ progenitor cells and can have implications on a variety of cell-based therapies. Stem Cells 2019;37:1528-1541.

Increased prevalence of coronary plaque in patients with psoriatic arthritis without prior diagnosis of coronary artery disease.

OBJECTIVES: To evaluate coronary atherosclerosis in patients with psoriatic arthritis (PsA) and control subjects using coronary CT angiography (CCTA). METHODS: Ninety consecutive patients with PsA (male: 56(62.2%); 50.3±11.1 years) were recruited. 240 controls (male: 137(57.1%); 49.6±10.7 years) without known cardiovascular (CV) diseases who underwent CCTA due to chest pain and/or multiple CV risk factors were recruited for comparison. RESULTS: Patients with PsA and controls were matched in age, gender and traditional CV risk factors (all p>0.2). The prevalence of overall plaque (54(60%)/84(35%), p<0.001), calcified plaque (CP) (29(32%)/40(17%), p=0.002), mixed plaque (MP) (20(22%)/18(8%), p<0.001), non-calcified plaque (NCP) (39(43%)/53(22%), p<0.001) and combined MP/NCP (46(51%)/62(26%), p<0.001) were all significantly higher in patients with PsA. Three-vessel disease was diagnosed in 12(13%) patients with PsA and 7(3%) controls (p<0.001), while obstructive plaques (>50% stenosis) were observed in 8(9%) patients with PsA and 7(3%) controls (p=0.033). After adjusting for traditional CV risk factors, PsA remained an independent explanatory variable for all types of coronary plaques (OR: 2.730 to 4.064, all p<0.001). PsA was also an independent explanatory variable for three-vessel disease (OR: 10.798, p<0.001) and obstructive plaque (3.939, p=0.024). In patients with PsA, disease duration was the only disease-specific characteristic associated with more vulnerable plaques (MP/NCP) in multivariate analysis (1.063, p=0.031). The other independent explanatory variables were age ≥55 years (5.636, p=0.005) and male gender (8.197, p=0.001). CONCLUSIONS: Patients with PsA have increased prevalence, burden and severity of coronary atherosclerosis as documented by CCTA. Longer disease duration was independently associated with the presence of vulnerable MP/NCP plaques in patients with PsA. TRIAL REGISTRATION NUMBER: NCT02232321.

The effects of golimumab on subclinical atherosclerosis and arterial stiffness in ankylosing spondylitis­a randomized, placebo-controlled pilot trial.

OBJECTIVE: Our aim was to ascertain the efficacy of golimumab compared with placebo in the prevention of atherosclerosis and arterial stiffness in AS. METHODS: A randomized, double-blind, placebo-controlled pilot study was performed in which AS patients were treated with golimumab (n = 20) and placebo (n = 21) for 12 months. Patients from the placebo group who failed to achieve a 20% response to Assessment of SpondyloArthritis international Society criteria (ASAS20) at 6 months received open-label golimumab. Intima-media thickness (IMT), pulse wave velocity (PWV) and augmentation index (AIx) were measured at baseline, 6 and 12 months. RESULTS: At 6 months, 11/20 (55%) and 3/21 (14%) patients from the golimumab and placebo groups achieved an ASAS20 response, respectively (P = 0.006). There was no significant difference in the change of the vascular parameters between the two groups. In the placebo group, significantly greater progression of the mean IMT [from 0.51 mm (S.D. 0.07) at baseline to 0.53 mm (S.D. 0.08) at 6 months, P = 0.044] and PWV (from 12.2 m/s (S.D. 1.6) at baseline to 12.6 m/s (S.D. 1.3), P = 0.028] were observed. There was a trend towards progression of the mean IMT in the golimumab group (P = 0.099) but the maximum IMT, PWV and AIx remained unchanged. At 12 months the changes in vascular parameters were similar between the early and delayed (or no) golimumab groups. CONCLUSION: Uncontrolled inflammation may result in a significant progression in IMT and PWV in patients with AS. Arterial dysfunction may be prevented by golimumab over a period of 6 months, probably because of effective suppression of inflammation. TRIAL REGISTRATION: clinicaltrials.gov (NCT01212653)

Predictors of functional deterioration in Chinese patients with psoriatic arthritis: a longitudinal study.

BACKGROUND: Psoriatic arthritis (PsA) disease activities at baseline may determine physical function over time. There is no longitudinal data on course of physical function in PsA patients from Asia. We aim to describe variables associated with a deterioration of physical function in PsA in Chinese over a 6-year period. METHODS: 125 consecutive patients with PsA fulfilled the CASPAR criteria from a rheumatology outpatient center were recruited to give sociodemographic and clinical data in 2006 to 2008. Follow up interviews were conducted in 2012 to 2013 to assess physical function using Health Assessment Questionnaire (HAQ). Regression models were constructed to determine baseline variables that predict physical function on follow up. RESULTS: A total of 97 patients completed the follow up survey, with mean follow up time of 6.2 (±0.7) years, response rate 77.6%. PsA patients had poor physical function and health related quality of life (HRQoL) compared to normal population. There were 33% who improved in disability status and 41.2% had persistent minimal disability by HAQ categories (HAQ 0-0.49) over time. There were 14.4% of the patients who had persistent moderate disability (HAQ 0.5-1.50) and 10.3% had deterioration in disability status. There were 17.5% of patients who had deterioration in physical function as defined by an increment of HAQ score of more than 0.2 at follow up survey. Age, physical function at baseline and the number of damaged joint were significantly related HAQ at follow up. CONCLUSION: Chinese patients with PsA had had poor physical function and quality of life. One fifth of patient experienced deterioration of physical function over time. Joint damage and baseline physical function were important factors associated with poor physical function in PsA over time.

Micrococcus Peritonitis Complicating Peritoneal Dialysis.

Peritonitis, a serious complication of peritoneal dialysis (PD), can be caused by opportunistic pathogens like Micrococcus species on rare occasions. We present a case of Micrococcus sp peritonitis in a 55-year-old female with end-stage kidney disease on continuous cycling peritoneal dialysis for one year who presented with cloudy effluent. Initial treatment against Micrococcus sp with vancomycin, gentamicin, and prophylactic oral nystatin was successful. However, one month later, the patient presented with abdominal pain and dialysate culture again grew Micrococcus sp. Treatment with vancomycin was unsuccessful in resolving culture positivity. The patient was transitioned to hemodialysis for non-medical reasons and then was later restarted on PD without further peritonitis episodes. Micrococcus sp peritonitis in PD poses treatment challenges due to limited guidelines. Intraperitoneal vancomycin is commonly used to target Micrococcus isolates although there is a high incidence of treatment failure. This case report highlights the need for continued reporting to enhance identification, prevention, and patient outcomes in Micrococcus sp peritonitis during PD.

Dynamics of a dengue disease transmission model with two-stage structure in the human population.

Age as a risk factor is common in vector-borne infectious diseases. This is partly because children depend on adults to take preventative measures, and adults are less susceptible to mosquito bites because they generally spend less time outdoors than children. We propose a dengue disease model that considers the human population as divided into two subpopulations: children and adults. This is in order to take into consideration that children are more likely than adults to be bitten by mosquitoes. We calculated the basic reproductive number of dengue, using the next-generation operator method. We determined the local and global stability of the disease-free equilibrium. We obtained sufficient conditions for the global asymptotic stability of the endemic equilibrium using the Lyapunov functional method. When the infected periods in children and adults are the same, we that the endemic equilibrium is globally asymptotically stable in the interior of the feasible region when the threshold quantity $ R_0 > 1 $. Additionally, we performed a numerical simulation using parameter values obtained from the literature. Finally, a local sensitivity analysis was performed to identify the parameters that have the greatest influence on changes in $ (R_0) $, and thereby obtain a better biological interpretation of the results.

Metabolic Basis of Cognitive Improvement Associated With Active B Vitamin Supplementation in Cognitively Impaired Elderly Subjects - A Metabolomics Study.

Intervention studies with active B vitamin supplementation in cognitively impaired individuals have yielded varying results in randomized controlled trials. In addition, a negative interaction of active B vitamin supplementation with aspirin usage on cognitive outcome was noted, but the molecular basis of the interaction has largely remained unknown. To investigate the metabolic basis of cognitive improvement brought about by active B vitamin supplementation, we conducted an extensive metabolomics analysis covering 302 identified metabolites on the baseline and 24-month serum samples from a cohort of 137 subjects randomly assigned to active supplementation or placebo. Pathway analysis uncovered enhanced gluconeogenesis and War-burg effects underlying cognitive improvement in non-aspirin users supplemented with active B vitamins. In addition, metabolomics revealed that aspirin usage may interact with B vitamin supplementation by altering gut microbial metabolism, particularly in terms of propionate production. Lastly, our omics data suggest that varying capacities to assimilate B vitamins at baseline, possibly mediated by differences in gut microbial composition, may underlie variations in inter-individual responses to active B vitamin supplementation.

A grassroots approach for greener education: An example of a medical student-driven planetary health curriculum.

Given the widespread impacts of climate change and environmental degradation on human health, medical schools have been under increasing pressure to provide comprehensive planetary health education to their students. However, the logistics of integrating such a wide-ranging and multi-faceted topic into existing medical curricula can be daunting. In this article, we present the Warren Alpert Medical School of Brown University as an example of a student-driven, bottom-up approach to the development of a planetary health education program. In 2020, student advocacy led to the creation of a Planetary Health Task Force composed of medical students, faculty, and administrators as well as Brown Environmental Sciences faculty. Since that time, the task force has orchestrated a wide range of planetary health initiatives, including interventions targeted to the entire student body as well as opportunities catering to a subset of highly interested students who wish to engage more deeply with planetary health. The success of the task force stems from several factors, including the framing of planetary health learning objectives as concordant with the established educational priorities of the Medical School's competency-based curriculum known as the Nine Abilities, respecting limitations on curricular space, and making planetary health education relevant to local environmental and hospital issues.

Serum Calprotectin Level Is Independently Associated With Carotid Plaque Presence in Patients With Psoriatic Arthritis.

Background: Whether calprotectin could play a role in augmenting cardiovascular (CV) risk in patients with psoriatic arthritis (PsA) remains uncertain. The aim of this study is to elucidate the association between serum calprotectin level and subclinical atherosclerosis in patient with PsA. Method: Seventy-eight PsA patients (age: 52 ± 10 years, 41 [52.6%] male) without CV disease were recruited into this cross-sectional study. Carotid intima-media thickness (cIMT) and the presence of plaque were determined by high-resolution ultrasound. Calprotectin levels in serum were quantified by enzyme-linked immunosorbent assay. The variables associated with the presence of carotid plaque (CP) were selected from the least absolute shrinkage and selection operator (LASSO) regression analysis. Results: 29/78 (37.2%) of patient had carotid plaque (CP+ group). Serum calprotectin level was significantly higher in the CP+ group (CP- group: 564.6 [329.3-910.5] ng/ml; CP+ group: 721.3 [329.3-910.5] ng/ml, P = 0.005). Serum calprotectin level correlated with PsA disease duration (rho = 0.280, P = 0.013) and mean cIMT (rho = 0.249, P = 0.038). Using LASSO regression analysis, the levels of Ln-calprotectin (OR: 3.38, 95% CI [1.37, 9.47]; P = 0.026) and PsA disease duration (OR: 1.09, 95% CI [1.01, 1.18]; P = 0.013) were screened out from a total of 19 variables. The model in predicting the presence of CP was constructed by Ln-calprotectin and PsA disease duration with an area under the receiver-operating characteristic (ROC) curve of 0.744, (95 CI% [0.59, 0.80], P = 0.037). Conclusion: Serum calprotectin level is associated with the presence of CP in PsA. Further studies are required to confirm whether this pathway is associated with CV events in PsA.

Comparison of carotid artery ultrasound and Framingham risk score for discriminating coronary artery disease in patients with psoriatic arthritis.

OBJECTIVES: This study aimed to assess the performance of carotid ultrasound (US) parameters alone or in combination with Framingham Risk Score (FRS) in discriminating patients with psoriatic arthritis (PsA) with and without coronary artery disease (CAD). METHODS: Ninety-one patients with PsA (56 males; age: 50±11 years, disease duration: 9.4±9.2 years) without overt cardiovascular (CV) diseases were recruited. Carotid intima-media thickness (cIMT), the presence of plaque and total plaque area (TPA) was determined by high-resolution US. CAD was defined as the presence of any coronary plaque on coronary CT angiography (CCTA). Obstructive-CAD (O-CAD) was defined as >50% stenosis of the lumen. RESULTS: Thirty-five (38%) patients had carotid plaque. Fifty-four (59%) patients had CAD (CAD+) and 9 (10%) patients had O-CAD (O-CAD+). No significant associations between the presence of carotid plaque and CAD were found. However, cIMT and TPA were higher in both the CAD+ and O-CAD+ group compared with the CAD- or O-CAD- groups, respectively. Multivariate logistic regression analysis revealed that mean cIMT was an independent explanatory variable associated with CAD and O-CAD, while maximum cIMT and TPA were independent explanatory variables associated with O-CAD after adjusting for covariates. The optimal cut-offs for detecting the presence of CAD were FRS >5% and mean cIMT at 0.62 mm (AUC: 0.71; sensitivity: 67%; specificity: 76%), while the optimal cut-offs for detecting the presence of O-CAD were FRS >10% in combination with mean cIMT at 0.73 mm (AUC: 0.71; sensitivity: 56%; specificity: 85%). CONCLUSION: US parameters including cIMT and TPA may be considered in addition to FRS for CV risk stratification in patients with PsA.

Is combination rituximab with cyclophosphamide better than rituximab alone in the treatment of lupus nephritis?

OBJECTIVE: To assess if combination rituximab and cyclophosphamide is more effective than rituximab monotherapy as an induction therapy for proliferative lupus nephritis. METHODS: A randomized open-label pilot study in which 9 patients received rituximab alone and 10 patients received two doses rituximab + intravenous cyclophosphamide. The clinical, laboratory and renal histological changes were assessed after 48 weeks of treatment. RESULTS: At week 48, four patients had a complete response, 11 patients achieved partial response, 2 patients remained the same or stable and 2 worsened. There were no statistical differences in the proportion of patients with complete or partial response between the two groups. None of the variables was an independent predictor of response at week 48. Nine patients had significant improvement in activity indices in renal biopsies, but there were no significant differences between the two groups. Overall, 18 out of 19 patients were found to have effective B-cell depletion. The median duration of complete B-cell depletion in all patients was 22 weeks. There were no statistically significant differences in the proportion of patients with complete depletion at weeks 4, 8, 24 and 48 between the two groups except at week 2. CONCLUSIONS: Rituximab monotherapy appears to be effective as induction therapy in lupus nephritis. The addition of cyclophosphamide offers no additional improvement in clinical, laboratory and renal histological assessment or the duration of B-cell depletion at 48 weeks. Large-scale studies with longer duration are needed to confirm these findings.

"A picture tells a thousand words" smartphone-based secure clinical image transfer improves compliance in open fracture management.

BACKGROUND: BOAST (British Orthopaedic Association Standards for Trauma) and NICE (National Institute of Clinical Excellence) guidelines recommend clinical photography of all open fractures on admission and at key stages of patient care for objective wound documentation and to avoid repeated examination. Recording and handling photographs in a compliant and confidential manner in the setting of acute trauma management can prove challenging. To facilitate clinical photography at our Major Trauma Centre (MTC) institution, a smartphone-based Secure Clinical Image Transfer (SCIT) app was introduced and integrated with the existing clinical photography database to allow clinicians to take photographs, which are saved directly to patient records. OBJECTIVES: To compare rates of information governance (IG)-compliant clinical photography of wounds of patients with open fractures before and after introduction of departmental smartphones loaded with the clinical photography app SCIT. METHODS: Admission lists were inspected retrospectively for patients admitted with open fractures between August and October 2016, before SCIT was introduced. The Trust clinical photography database was searched for corresponding patient images and where present, graded out of three for clarity, comprehensiveness and context. The procedure was repeated prospectively from August to October 2017 after rollout of SCIT. The uptake and quality of photography were statistically compared (Fisher's exact test, significance level p < 0.05). RESULTS: 42 open fractures were identified in the 2016 period and 40 in the 2017 period. None of the 42 patients in the 2016 cohort had records of IG-compliant clinical photography on admission. 16 of 40 patients in the 2017 cohort had IG-compliant clinical photography on admission. This was statistically significant (p < 0.0001). 5 of 42 patients in the 2016 cohort and 8 of 40 patients in the 2017 cohort had photographs after first debridement. This was statistically insignificant (p = 0.375). All five photographs in the 2016 cohort scored 3/3. 18 of 21 photographs in the 2017 cohort scored 3/3, one scored 2/3 and two scored 1/3. CONCLUSIONS: Integrating commonplace smartphone technology with a secure platform for taking and storing photographs can improve rates of IG-compliant clinical photography of open fractures. This may improve documentation, communication and patient care.

Simultaneous in vivo optical quantification of key metabolic and vascular endpoints reveals tumor metabolic diversity in murine breast tumor models.

Therapeutically exploiting vascular and metabolic endpoints becomes critical to translational cancer studies because altered vascularity and deregulated metabolism are two important cancer hallmarks. The metabolic and vascular phenotypes of three sibling breast tumor lines with different metastatic potential are investigated in vivo with a newly developed quantitative spectroscopy system. All tumor lines have different metabolic and vascular characteristics compared to normal tissues, and there are strong positive correlations between metabolic (glucose uptake and mitochondrial membrane potential) and vascular (oxygen saturations and hemoglobin concentrations) parameters for metastatic (4T1) tumors but not for micrometastatic (4T07) and nonmetastatic (67NR) tumors. A longitudinal study shows that both vascular and metabolic endpoints of 4T1 tumors increased up to a specific tumor size threshold beyond which these parameters decreased. The synchronous changes between metabolic and vascular parameters, along with the strong positive correlations between these endpoints suggest that 4T1 tumors rely on strong oxidative phosphorylation in addition to glycolysis. This study illustrates the great potential of our optical technique to provide valuable dynamic information about the interplay between the metabolic and vascular status of tumors, with important implications for translational cancer investigations.

Circulating miR-99b-5p as a novel predictor of erosion progression on high-resolution peripheral quantitative computed tomography in early rheumatoid arthritis: A prospective cohort study.

OBJECTIVES: To compare micro RNA (miRNA) expression: (a) between healthy individuals and early rheumatoid arthritis (ERA) patients with and without erosion on high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline; and (b) to explore whether these miRNAs could inform a signature predictive of erosion progression despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). METHODS: The second metacarpophalangeal head (MCP2) was scanned by HR-pQCT at baseline and 1 year in 117 ERA patients. We performed global profiling of 377 miRNAs in 10 ERA patients with and without erosion on HR-pQCT at baseline and six healthy controls. Validation of the miRNAs of interest were conducted using TaqMan® quantitative real-time polymerase chain reaction in the validation ERA cohort (n = 117) at baseline. Correlation between the candidate miRNAs and erosion progression over 1 year were also assessed. RESULTS: In the 377 screened miRNAs, 94 (60.6%) miRNAs were upregulated in patients with erosions, with 13 (8.4%) upregulated more than 2-fold. Sixty-one (39.4%) miRNAs were downregulated in patients with erosions, with 6 (3.9%) downregulated more than 2-fold. Expression of miR-143-3p, miR-145-5p and miR-99b-5p were significantly higher in the plasma of ERA patients with erosions compared with those without erosions. Logistic regression analysis revealed that the baseline expression of miR-99b-5p was an independent predictor of erosion progression at month 12 (Exp [B] = 4.257, 95% CI 1.178-15.386, P = 0.027). CONCLUSIONS: Differential expressions of circulating miR-143-3p, miR-145-5p and miR-99b-5p in the plasma of ERA patients may characterize a severe form of the disease. MiR-99b-5p, in particular, may serve as a possible predictor for erosion progression.