Comparison of Fecal Calprotectin and Myeloperoxidase in Predicting Outcomes in Inflammatory Bowel Disease.

BACKGROUND: Biomarkers have been proposed as surrogate treatment targets for the management of inflammatory bowel disease (IBD); however, their relationship with IBD-related complications remains unclear. This study investigated the utility of neutrophil biomarkers fecal calprotectin (fCal) and fecal myeloperoxidase (fMPO) in predicting a complicated IBD course. METHODS: Participants with IBD were followed for 24 months to assess for a complicated IBD course (incident corticosteroid use, medication escalation for clinical disease relapse, IBD-related hospitalizations/surgeries). Clinically active IBD was defined as Harvey-Bradshaw index >4 for Crohn's disease (CD) and simple clinical colitis activity index >5 for ulcerative colitis (UC). Area under the receiver-operating-characteristics curves (AUROC) and multivariable logistic regression assessed the performance of baseline symptom indices, fCal, and fMPO in predicting a complicated disease IBD course at 24 months. RESULTS: One hundred and seventy-one participants were included (CD, n = 99; female, n = 90; median disease duration 13 years [interquartile range, 5-22]). Baseline fCal (250 µg/g; AUROC = 0.77; 95% confidence interval [CI], 0.69-0.84) and fMPO (12 µg/g; AUROC = 0.77; 95% CI, 0.70-0.84) predicted a complicated IBD course. Fecal calprotectin (adjusted OR = 7.85; 95% CI, 3.38-18.26) and fMPO (adjusted OR = 4.43; 95% CI, 2.03-9.64) were associated with this end point after adjustment for other baseline variables including clinical disease activity. C-reactive protein (CRP) was inferior to fecal biomarkers and clinical symptoms (pdifference < .05) at predicting a complicated IBD course. A combination of baseline CRP, fCal/fMPO, and clinical symptoms provided the greatest precision at identifying a complicated IBD course. CONCLUSIONS: Fecal biomarkers are independent predictors of IBD-related outcomes and are useful adjuncts to routine clinical care.

Changes to insulin sensitivity in glucose clearance systems and redox following dietary supplementation with a novel cysteine-rich protein: A pilot randomized controlled trial in humans with type-2 diabetes.

We recently developed a novel keratin-derived protein (KDP) rich in cysteine, glycine, and arginine, with the potential to alter tissue redox status and insulin sensitivity. The KDP was tested in 35 human adults with type-2 diabetes mellitus (T2DM) in a 14-wk randomised controlled pilot trial comprising three 2×20 g supplemental protein/day arms: KDP-whey (KDPWHE), whey (WHEY), non-protein isocaloric control (CON), with standardised exercise. Outcomes were measured morning fasted and following insulin-stimulation (80 mU/m2/min hyperinsulinaemic-isoglycaemic clamp). With KDPWHE supplementation there was good and very-good evidence for moderate-sized increases in insulin-stimulated glucose clearance rate (GCR; 26%; 90% confidence limits, CL 2%, 49%) and skeletal-muscle microvascular blood flow (46%; 16%, 83%), respectively, and good evidence for increased insulin-stimulated sarcoplasmic GLUT4 translocation (18%; 0%, 39%) vs CON. In contrast, WHEY did not effect GCR (-2%; -25%, 21%) and attenuated HbA1c lowering (14%; 5%, 24%) vs CON. KDPWHE effects on basal glutathione in erythrocytes and skeletal muscle were unclear, but in muscle there was very-good evidence for large increases in oxidised peroxiredoxin isoform 2 (oxiPRX2) (19%; 2.2%, 35%) and good evidence for lower GPx1 concentrations (-40%; -4.3%, -63%) vs CON; insulin stimulation, however, attenuated the basal oxiPRX2 response (4%; -16%, 24%), and increased GPx1 (39%; -5%, 101%) and SOD1 (26%; -3%, 60%) protein expression. Effects of KDPWHE on oxiPRX3 and NRF2 content, phosphorylation of capillary eNOS and insulin-signalling proteins upstream of GLUT4 translocation AktSer437 and AS160Thr642 were inconclusive, but there was good evidence for increased IRSSer312 (41%; 3%, 95%), insulin-stimulated NFκB-DNA binding (46%; 3.4%, 105%), and basal PAK-1Thr423/2Thr402 phosphorylation (143%; 66%, 257%) vs WHEY. Our findings provide good evidence to suggest that dietary supplementation with a novel edible keratin protein in humans with T2DM may increase glucose clearance and modify skeletal-muscle tissue redox and insulin sensitivity within systems involving peroxiredoxins, antioxidant expression, and glucose uptake.

A three-arm single blind randomised control trial of naïve medical students performing a shoulder joint clinical examination.

BACKGROUND: Technological advances have previously been hailed as a new dawn in Higher Education, with the advent of 'massive open online courses' (MOOCs) and online learning. Virtual platforms have potential advantages such as accessibility and availability but simply transferring educational material to the online environment may not ensure high quality learning. Clinical examination is a fundamental principle of medical assessment, and this study aimed to assess the role of technology in teaching these skills. AIMS/OBJECTIVES: To determine whether three teaching modalities were of equal efficacy in teaching examination of the shoulder joint to naïve medical students. METHODS: Sixty-seven pre-clinical medical students naïve to large joint examination were recruited. Participants completed a learning style questionnaire and were then block randomised to three study: textbook study, face-to-face seminar, or video tutorial via online platform. The same examination technique was taught in all groups, with the intervention being the method of delivery All second year students were eligible for inclusion. The single exclusion criteria was previous exposure to clinical examination teaching. Students were assessed using a standardised scoring system at baseline (pre-intervention), and days 5 and 19 post-intervention (maximum score 30). Assessors were blinded to group allocation. The primary outcome was assessment score at day 5 post intervention. RESULTS: There was no difference between the three groups at baseline assessment (mean scores 2.4 for textbook, 2.8 for face-to-face, and 3.1 for video; p = 0.267). Mean post-intervention scores were 16.5 textbook, 25.5 face-to-face, and 22.4 video (p < 0.001, η2 = .449). There was no change between day 5 and day 19 post-intervention assessment scores in any group (p = 0.373), Preferred learning style did not affect scores (p = 0.543). CONCLUSION: Face-to-face teaching was the most effective method for teaching clinical examination of the shoulder. Technology can potentially increase accessibility and remove geographic barriers, but is not as effective if teaching techniques are simply mirrored in an online format. Online platforms allow in depth data analysis of how learners interact with educational material and this may have value in improving the design of online educational materials, and is a potential area for further research.

Hypersensitivity reaction after administration of rivaroxaban (Xarelto).

Little has been documented regarding hypersensitivity reactions with rivaroxaban or other factor Xa inhibitors. We report the development of a hypersensitivity reaction to rivaroxaban in a 64-year-old African American male patient who presented to the emergency department and was subsequently evaluated in dermatology consultation and follow-up. This case highlights the vigilance required by health care workers in recognizing potential adverse effects of newer anticoagulation therapy and in making medication changes where necessary.

Reoperative Parathyroidectomy: Overly Descended Superior Adenoma.

OBJECTIVES: To identify the importance of the ectopic, overly descended superior parathyroid adenoma variant and its prevalence in primary and reoperative parathyroid surgery and the implications for successful initial parathyroidectomy. STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary endocrine surgery practice in an academic medical center. SUBJECTS AND METHODS: An analysis was undertaken of 561 consecutive patients undergoing parathyroid surgery in a tertiary endocrine surgery practice from March 2004 to April 2013. There were 270 patients who had curative primary or reoperative surgery for single-gland parathyroid adenomas during this time. Clinical records, imaging studies, operative reports, and pathology findings were evaluated, and cases from a subset of patients who had an ectopic, overly descended superior parathyroid adenoma were further analyzed. The prevalence of this entity in primary and revision surgeries was calculated. RESULTS: Among the 270 patients with single-gland parathyroid adenomas, there were 251 primary operations and 19 reoperative procedures referred from outside institutions. An ectopic, overly descended superior parathyroid adenoma was present in 23 (9.2%) primary cases and 4 (21.1%) reoperative cases. CONCLUSION: An overly descended superior parathyroid adenoma is frequently encountered during primary parathyroid surgery. It is more than twice as common in reoperative parathyroidectomy, reflecting the propensity to be missed at the first exploration. Recognition and proper treatment of this entity at the initial operation will reduce the need for revision surgery.

Locked rigid antegrade intramedullary nailing of adolescent femoral fractures using a lateral trochanteric entry point.

The purpose of this study is to present our experience of treating adolescent femoral fractures using a locked intramedullary nail with a lateral trochanteric entry point. We retrospectively reviewed 15 femoral fractures in 13 adolescents who were treated in our unit between 2011 and 2014. Data collected included patient demographics, mechanism of injury, type of fracture, associated injuries, time to union and complications. A radiographic review was also undertaken. The mean time to radiological union in 14 out of the 15 fractures was 13 weeks (range, 10-20 weeks). One patient had a delayed union that required bone grafting and united finally at 30 weeks post injury. The mean difference in the neck shaft angle between the operated and non-operated side was 1.5 degrees (range : -10 to 10 degrees). No patients had infection or avascular necrosis. Five nails were removed after the fractures had healed without complications. Locked rigid intramedullary nailing of adolescent femoral fractures is a safe and effective treatment option when the lateral aspect of the greater trochanter is used as an entry point.

An urban trauma centre experience with abdominal vena cava injuries.

BACKGROUND: The aim of the study was to present the surgical management of injuries to the abdominal vena cava (AVC) and to identify clinical and physiological factors and management strategies which affect the outcome. METHOD: A retrospective review was conducted of AVC injuries in patients attending the trauma centre at Groote Schuur Hospital, Cape Town, from January 2003 to December 2011. Demographic data, mechanism and agent of injury, level of injury, physiological parameters, associated injuries, trauma scores, management strategy, morbidity and mortality, and length of hospital stay were taken from the trauma centre's operative databank at Groote Schuur Hospital. RESULTS: Thirty-fi ve patients with AVC injuries were identifi ed. There were 33 penetrating injuries (94%). Gunshot wounds accounted for 28 of them (85%). There were 19 (54%) infrarenal, 9 (26%) juxtarenal, 3 (7%) suprarenal and 4 (11%) retrohepatic AVC injuries. Most patients were treated with ligation (66%). There were 17 (49%) deaths. There were signifi cant differences in the preoperative systolic blood pressure (p = 0.044), number of red cell units transfused (p = 0.001), serum lactate (p = 0.007), arterial pH (p = 0.002) and preoperative temperature (p = 0.000) between the survivors and non-survivors. There was also a signifi cant difference in ligation versus repair between the two groups (p = ≤ 0.000). There was no difference in the injury severity, level of injury and the number of associated injuries between survivors and non-survivors. CONCLUSION: AVC injuries are associated with high mortality. Patients presenting with clinical and physiological evidence of shock and who require "damage control" surgery are more likely to suffer a worse outcome, particularly when multiple physiological deragements are present. Patients who died often have severe associated injuries.

Hypothalamic gene expression underlying pre-hibernation satiety.

Prior to hibernation, 13-lined ground squirrels (Ictidomys tridecemlineatus) enter a hypophagic period where food consumption drops by an average of 55% in 3 weeks. This occurs naturally, while the ground squirrels are in constant environmental conditions and have free access to food. Importantly, this transition occurs before exposure to hibernation conditions (5°C and constant darkness), so the ground squirrels are still maintaining a moderate level of activity. In this study, we used the Illumina HiSeq 2000 system to sequence the hypothalamic transcriptomes of ground squirrels before and after the autumn feeding transition to examine the genes underlying this extreme change in feeding behavior. The hypothalamus was chosen because it is known to play a role in the control and regulation of food intake and satiety. Overall, our analysis identified 143 genes that are significantly differentially expressed between the two groups. Specifically, we found five genes associated with feeding behavior and obesity (VGF, TRH, LEPR, ADIPOR2, IRS2) that are all upregulated during the hypophagic period, after the feeding transition has occurred. We also found that serum leptin significantly increases in the hypophagic group. Several of the genes associated with the natural autumnal feeding decline in 13-lined ground squirrels show parallels to signaling pathways known to be disrupted in human metabolic diseases, like obesity and diabetes. In addition, many other genes were identified that could be important for the control of food consumption in other animals, including humans.

EFM data mapped into 2D images of tip-sample contact potential difference and capacitance second derivative.

We report a simple technique for mapping Electrostatic Force Microscopy (EFM) bias sweep data into 2D images. The method allows simultaneous probing, in the same scanning area, of the contact potential difference and the second derivative of the capacitance between tip and sample, along with the height information. The only required equipment consists of a microscope with lift-mode EFM capable of phase shift detection. We designate this approach as Scanning Probe Potential Electrostatic Force Microscopy (SPP-EFM). An open-source MATLAB Graphical User Interface (GUI) for images acquisition, processing and analysis has been developed. The technique is tested with Indium Tin Oxide (ITO) and with poly(3-hexylthiophene) (P3HT) nanowires for organic transistor applications.

Nanobubbles and the nanobubble bridging capillary force.

Interactions between hydrophobic surfaces at nanometer separation distances in aqueous solutions are important in a number of biological and industrial processes. Force spectroscopy studies, most notably with the atomic force microscope and surface-force apparatus, have found the existence of a long range hydrophobic attractive force between hydrophobic surfaces in aqueous conditions that cannot be explained by classical colloidal science theories. Numerous mechanisms have been proposed for the hydrophobic force, but in many cases the force is an artifact due to the accumulation of submicroscopic bubbles at the liquid-hydrophobic solid interface, the so called nanobubbles. The coalescence of nanobubbles as hydrophobic surfaces approach forms a gaseous capillary bridge, and thus a capillary force. The existence of nanobubbles has been highly debated over the last 15 years. To date, experimental evidence is sound but a theoretical understanding is still lacking. It is the purpose of this review to bring together the many experimental results on nanobubbles and the resulting capillary force in order to clarify these phenomena. A review of pertinent nanobubble stability and formation theories is also presented.

Audit of appendicectomies at Frere Hospital, Eastern Cape.

OBJECTIVE: We sought to evaluate the surgical service in the central part of the Eastern Cape Province by reviewing the practice of appendicectomy at Frere Hospital. Specifically, it was our aim to compare the service to those patients who reside in and outside the East London metropolitan area and the outcomes of patients according to their operative finding. PATIENTS AND METHODS: A retrospective study was performed on the medical records of all patients who underwent appendicectomy in a 26-month period. This entailed a thorough review of demographic factors, mode of presentation, operation factors and findings, and the postoperative course. RESULTS: . In the study period, 436 appendicectomies were performed, of which 81% were performed after hours, with a consultant surgeon present in only 6% of cases. Of the group, 51% had a perforated appendix at surgery, and 12% a normal appendix. There was a significantly increased risk of perforation at the extremes of age and in patients from outside East London (63% v. 35% in East London). Those with perforated appendices stayed an average of 7.3 days in hospital, compared with 5 days for those with earlier appendicitis. Of the perforated group, 21% developed a complication, with 86% of all complications occurring in this group. The hospital stays were longer in those perforated appendices that were drained (10.7 days v. 6.1 days), and the rate of complications higher in this subgroup. Four patients died (1%)--all in the perforated group. DISCUSSION: The perforation rate in our setting is significantly higher than other published results. Patients with perforated appendices have longer hospital stays and are more likely to develop significant complications, including re-operation. Patients from outside East London, males and those at the extremes of age are more likely to have perforated appendices. This study lends little support to the advocates of drains, and recommends the use of non-absorbable sutures for skin closure. The majority of procedures are performed after hours by medical officers and registrars, but there is no evidence to suggest that this practice be altered, particularly in light of the high perforation rate. The main factor identified as contributing to the huge discrepancy between perforation rates (and hence morbidity) is delay in presentation to the operating surgeon for the region. Patient factors may contribute, but service factors are regarded as significant, including poor access to clinics and hospitals, transport and ambulance services, and the expertise of the referring medical staff. The need to improve the quality of patient care in the under-serviced rural areas of the Eastern Cape is highlighted.

Effects of examiner error on neuropsychological test results in a multi-site study.

This study compared the difference between original and "corrected" neuropsychological test scores at baseline and following 1 year of experience in 17 non-psychology trained examiners. Test protocols were reviewed for errors in instruction, administration, recording, and scoring. Fewer than 3% of the test scaled scores showed a correction of greater than 1 SD. At baseline, individual test scores that changed T-score classification occurred on Digit Symbol, Trails B, and Logical Memory I and II. At one year, significant classification changes remained for Logical Memory I and II (25% and 15%). Scoring of subjective tests remains problematic and centralized re-scoring is recommended.

Training and management of a multisite neuropsychological testing protocol for the Department of Veterans Affairs cooperative study evaluating on- and off-pump coronary artery bypass graft procedures.

Research study coordinators from 17 sites participating in a cardiac surgery study were trained to administer and score a brief neuropsychological test battery. Results were sent to the study's centralized laboratory for review and feedback. The average examiner errors on the first six protocols were compared with the average errors on the last six protocols over 12 months for each site. Overall, errors for the first six protocols were 4.42, and errors for the last six protocols were 1.83, representing a significant overall decline. Errors for instruction, administration, and recording showed a significant decrease over time. Despite ongoing feedback to examiners, scoring errors did not decline significantly overall; this suggests that a review of all protocols is necessary to achieve reliable scoring. However, when examiners' number of protocols completed was compared with number of scoring errors per protocol, there was a trend for examiners who had completed more protocols to show more improvement in scoring.

The role of oxidants and vitamin C on neutrophil apoptosis and clearance.

We have investigated the role of neutrophil oxidants in the surface changes that result in recognition and uptake of neutrophils by macrophages. We have shown that H2O2 produced by stimulated neutrophils is essential for the surface expression of phosphatidylserine. This does not occur in neutrophils from mice with chronic granulomatous disease and may explain the formation of granuloma in this condition. We have also investigated the role of intracellular vitamin C on neutrophil apoptosis. Cells from vitamin C-deficient mice were found to be less likely to undergo both spontaneous and oxidant-induced apoptosis, with eventual necrosis being the most probable outcome.

Collaborative investigation of an outbreak of Salmonella enterica serotype Newport in England and Wales in 2001 associated with ready-to-eat salad vegetables.

In June 2001, as part of a microbiological study of bagged, ready-to-eat salad products, Salmonella enterica serotype Newport was isolated from a sample of pre-packed green salad distributed by a major supermarket retailer. The strain was characterised by phage typing, plasmid profile typing and pulsed-field gel electrophoresis. Other isolates of S. Newport from cases of human infection in England and Wales in the first six months of 2001 were similarly characterised. Of 60 strains from cases of human infection, 19 were found to be indistinguishable from that isolated from the salad product. This study highlights the benefits of an integrated approach to outbreak investigations, involving the various elements of the PHLS and the Food Standards Agency, and acknowledges the full co-operation of the retailer in ensuring the rapid withdrawal of the contaminated product.

Regulation of apoptosis by vitamin C. Specific protection of the apoptotic machinery against exposure to chlorinated oxidants.

We have investigated the ability of intracellular vitamin C to protect human umbilical vein endothelial cells from exposure to hypochlorous acid (HOCl) and a range of derived chloramines. Ascorbate provided minimal protection against the cytotoxicity induced by these oxidants, as measured by propidium iodide uptake. In contrast, there was a marked effect on apoptosis, monitored by caspase-3 activation and phosphatidylserine exposure. Extended incubation of the cells with glycine chloramine or histamine chloramine completely blocked apoptosis initiated in the cells by serum withdrawal. This effect was significantly abrogated by ascorbate. Inhibition of apoptosis required the oxidant to be present for an extended period after serum withdrawal and occurred prior to caspase-3 activation. General protection of thiols by ascorbate was not responsible for the protection of apoptosis, because intracellular oxidation by HOCl or chloramines was not prevented in supplemented cells. The results suggest a new role for vitamin C in the regulation of apoptosis. We propose that, by protection of an oxidant-sensitive step in the initiation phase, ascorbate allows apoptosis to proceed in endothelial cells under sustained oxidative stress.

Women's experience of traumatic stress in cancer treatment.

In this study we investigated gender differences in the prevalence and predictors of posttraumatic stress disorder (PTSD) in a sample of cancer patients. Eighty-seven patients (59 women and 28 men) recruited from a local cancer clinic completed measures of individual coping style, social support resources, symptoms of PTSD, and the nature of the trauma associated with these symptoms. PTSD symptoms were more frequently reported by women (27% versus 10%). Predictors of PTSD for women were (1) perceived intensity of cancer treatment; (2) problems with health care professionals; (3) and cognitive avoidant coping style. For men, the sole predictor of elevated PTSD scores was behavioral avoidance. Women reported significantly higher levels of treatment intensity (TI), greater numbers and types of treatment, and more problems with health care professionals. Interpersonal and relational aspects of their illness were reported as most stressful, compared with men who were more concerned with work and finances. These differences may, in part, reflect an androcentric model of cancer treatment, which women experience as particularly stressful.

Being Indian: strengths sustaining First Nations peoples in Saskatchewan residential schools.

This qualitative study asked the question: what were the strengths that contributed to the survival of First Nations peoples during their stay in residential schools? Six elders who are survivors of residential schools in southern Saskatchewan were asked to respond in narrative form to this research question. Analysis of interviews revealed that, drawing on community-building skills of First Nations cultures, they created their own community with each other within the confines of this oppressive environment. The strengths they identified are consistent with sense of community identified in community psychological literature, yet are also unique to First Nations cultures. These strengths are: autonomy of will and spirit, sharing, respect, acceptance, a strong sense of spirituality, humour, compassion, and cultural pride. It is suggested that community-based mental health initiatives which identify traditional sources of strengths within First Nations communities will be most effective in promoting healing from residential school trauma.