Histomorphology of the subregions of the scapholunate ligament and its enthesis

Background  The scapholunate interosseous ligament (SLIL) has three subregions: dorsal, proximal, and volar. The SLIL enthesis has not previously been studied despite its important mechanical function in wrist joint biomechanics. Questions/Purposes  This study aims to compare the histomorphological differences between the SLIL subregions, including at their entheses. Three questions are explored: Do the gross dimensions differ between SLIL subregions? Does the enthesis qualitatively, and its calcified fibrocartilage (CF) quantitatively, differ between (a) SLIL subregions and (b) scaphoid and lunate attachments? Methods  Twelve fresh-frozen human cadaveric wrists were dissected and the gross dimensions of the SLIL subregions measured. Subregions were histologically processed for morphological and compositional analyses, including quantification of enthesis CF area. Results  The dorsal subregion was the thickest. The dorsal and volar subregions had fibrocartilaginous entheses, while the proximal subregion was attached to articular cartilage. The dorsal subregion had significantly more CF than the volar subregion. There was no significant difference in the enthesis CF between scaphoid and lunate attachments in the three subregions. Conclusions  There are significant morphological differences between the SLIL subregions. The dorsal subregion has the largest amount of CF, which is consistent with the greater biomechanical force subjected to this subregion. The similar histomorphology of the ligament at the scaphoid and lunate entheses suggests that similar biomechanical forces are applied to both attachments. Clinical Relevance  The histomorphological results confirm that the dorsal subregion is the strongest of the three subregions. The results from the entheseal region may have important implications in the study of graft incorporation during SLIL reconstruction

Regression correction equation to adjust serum iron and ferritin concentrations based on C-reactive protein and albumin in patients receiving primary and secondary care

Background: Systemic inflammation, even at low levels, can greatly interfere with measures of iron status, making diagnosis of iron deficiency difficult. The objective of the present study was to create linear regression correction equations to adjust serum ferritin and iron concentrations based on measurements of the acute-phase proteins C-reactive protein (CRP) and albumin. Methods: Data from a cohort (1) of patients (n = 7226) in primary and secondary care who had serum ferritin, iron, CRP, and albumin measured at the same time point were examined. Linear regression coefficients were calculated for CRP and albumin with serum iron and ferritin as the outcome variables. Patients with ferritin <15 µg/L or serum iron <10 µmol/L were categorized as iron deficient. The equation was then applied to a cohort (2) of patients with colorectal cancer who had ferritin and iron measured preoperatively ( n = 356). Results: In cohort 1 there was a significant difference in the proportions of patients with serum ferritin <15 µg/L and serum iron <10 µmol/L, respectively, when the unadjusted (7% and 55%), adjusted based on CRP alone (13% and 26%), adjusted based on albumin alone (11% and 37%), and adjusted based on both CRP and albumin (24% and 15%) values were compared (both P < 0.001). In cohort 2 there was a significant difference in the proportions of patients with serum ferritin <15 µg/L and serum iron <10 µmol/L, respectively, when the unadjusted (28% and 66%), adjusted based on CRP alone (39% and 57%), adjusted based on albumin alone (39% and 59%), and adjusted based on both CRP and albumin (46% and 44%) values were compared (P < 0.001 and P < 0.004). Conclusions: In both cohorts the greatest increase in the proportion of patients meeting definitions of iron deficiency was found when adjustment was made for both CRP and albumin together. Even low levels of inflammation had a significant effect on serum iron and ferritin values

Nuclear Dbf2-related protein kinases (NDRs) in isolated cardiac myocytes and the myocardium: activation by cellular stresses and by phosphoprotein serine-/threonine-phosphatase inhibitors

The nuclear Dbf2-related protein kinases 1 and 2 (NDR1/2) are closely-related AGC family kinases that are strongly conserved through evolution. In mammals, they are activated inter alia by phosphorylation of an hydrophobic domain threonine-residue [NDR1(Thr-444)/NDR2(Thr-442)] by an extrinsic protein kinase followed by autophosphorylation of a catalytic domain serine-residue [NDR1(Ser-281)/NDR2(Ser-282)]. We examined NDR1/2 expression and regulation in primary cultures of neonatal rat cardiac myocytes and in perfused adult rat hearts. In myocytes, transcripts for NDR2, but not NDR1, were induced by the hypertrophic agonist, endothelin-1. NDR1(Thr-444) and NDR2(Thr-442) were rapidly phosphorylated (maximal in 15-30 min) in myocytes exposed to some phosphoprotein Ser-/Thr-phosphatase 1/2 inhibitors (calyculin A, okadaic acid) and, to a lesser extent, by hyperosmotic shock, low concentrations of H(2)O(2), or chelerythrine. In myocytes adenovirally-transduced to express FLAG-NDR2 (which exhibited a mainly-cytoplasmic localisation), the same agents increased FLAG-NDR2 activity as assessed by in vitro protein kinase assays, indicative of FLAG-NDR2(Ser-282/Thr-442) phosphorylation. Calyculin A-induced phosphorylation of NDR1(Thr-444)/NDR2(Thr-442) and activation of FLAG-NDR2 were inhibited by staurosporine, but not by other protein kinase inhibitors tested. In ex vivo rat hearts, NDR1(Thr-444)/NDR2(Thr-442) were phosphorylated in response to ischaemia-reperfusion or calyculin A. From a pathological viewpoint, we conclude that activities of NDR1 and NDR2 are responsive to cytotoxic stresses in heart preparations and this may represent a previously-unidentified response to myocardial ischaemia in vivo

Nonlinear Structural Analysis Methodology and Dynamics Scaling of Inflatable Parabolic Reflector Antenna Concepts

Ultra-light weight and ultra-thin membrane inflatable antenna concepts are fast evolving to become the state-of-the-art antenna concepts for deep-space applications. NASA Langley Research Center has been involved in the structural dynamics research on antenna structures. One of the goals of the research is to develop structural analysis methodology for prediction of the static and dynamic response characteristics of the inflatable antenna concepts. This research is focused on the computational studies to use nonlinear large deformation finite element analysis to characterize the ultra-thin membrane responses of the antennas. Recently, structural analyses have been performed on a few parabolic reflector antennas of varying size and shape, which are referred in the paper as 0.3 meters subscale, 2 meters half-scale, and 4 meters full-scale antenna. The various aspects studied included nonlinear analysis methodology and solution techniques, ways to speed convergence in iterative methods, the sensitivities of responses with respect to structural loads, such as inflation pressure, gravity, and pretension loads in the ground and in-space conditions, and the ultra-thin membrane wrinkling characteristics. Several such intrinsic aspects studied have provided valuable insight into evaluation of structural characteristics of such antennas. While analyzing these structural characteristics, a quick study was also made to assess the applicability of dynamics scaling of the half-scale antenna. This paper presents the details of the nonlinear structural analysis results, and discusses the insight gained from the studies on the various intrinsic aspects of the analysis methodology. The predicted reflector surface characteristics of the three inflatable ultra-thin membrane parabolic reflector antenna concepts are presented as easily observable displacement fringe patterns with associated maximum values, and normal mode shapes and associated frequencies. Wrinkling patterns are presented to show how surface wrinkle progress with increasing tension loads. Antenna reflector surface accuracies were found to be very much dependent on the type and size of the antenna, the reflector surface curvature, reflector membrane supports in terms of spacing of catenaries, as well as the amount of applied load

Quantitative data on red cell measures of iron status and their relation to the magnitude of the systemic inflammatory response and survival in patients with colorectal cancer

Background: Inflammation is recognised to be associated with perturbation of serum measures of iron status. However, the impact of colorectal cancer associated host inflammation on red cell measures of iron status has not been previously quantified. Methods: Patients undergoing elective surgery with curative intent, for colorectal cancer, at a single centre between 2008 and 2017 were included (n = 824). Blood samples taken for C-reactive protein (CRP), albumin, and full blood count (FBC) allowed patients to be grouped by modified Glasgow Prognostic Score (mGPS), and anaemia subtype (haemoglobin (Hb) M < 130 mg/L and F < 120 mg/L, with microcytic anaemia being mean corpuscular volume (MCV) < 80 f/L, and normocytic anaemia with MCV 80–100 f/L). Relationships between these groupings and red cell measures iron status including Hb, MCV, mean corpuscular haemoglobin (MCH) and red cell distribution width (RDW) were examined. Results: The combination of increasing T stage and increasing mGPS was associated with lower Hb, lower MCV, lower MCH, higher RDW, and higher prevalence of both microcytic and normocytic anaemia (all p < 0.001). The combination of CRP >10 mg/L and albumin <35  g/L was associated with lower Hb, lower MCV, lower MCH, higher RDW, and higher prevalence of both microcytic and normocytic anaemia (all p < 0.010). At multivariate Cox regression only Hb remained significantly associated with cancer specific (HR 0.98, 95% CI 0.97–0.99, p < 0.001), and overall survival (HR 0.98, 95% CI 0.97–0.99, p = 0.001). Conclusions: The presence of a host systemic inflammatory response to colorectal cancer was associated with significant perturbation of red cell measure of iron status

Perioperative blood transfusion is associated with the postoperative systemic inflammatory response and poorer outcomes following surgery for colorectal cancer

Background: The present study investigated relationships between perioperative blood transfusion, postoperative systemic inflammatory response, and outcomes following surgery for colorectal cancer. Methods: Data were recorded for patients (n = 544) undergoing potentially curative, elective surgery for colorectal cancer at a single center between 2012 and 2017. Transfusion history was obtained retrospectively from electronic records. Associations between blood transfusion, postoperative C-reactive protein (CRP), albumin, hemoglobin, complications, cancer-specific survival and overall survival (OS) were assessed using propensity score matching (n =116). Results: Of 544 patients, the majority were male (n =294, 54%), over 65 years of age (n =350, 64%), and with colonic (n =347, 64%) node-negative disease (n =353, 65%). Eighty-six patients (16%) required perioperative blood transfusion. In the unmatched cohort, blood transfusion was associated with higher median postoperative day (POD) 3 CRP {143 [interquartile range (IQR) 96–221 mg/L] vs. 120 (IQR 72–188 mg/L); p = 0.004}, lower median POD 3 albumin [24 (IQR 20–26 g/L) vs. 27 (IQR 24–30 g/L); p < 0.001], more postoperative complications [odds ratio (OR) 3.28, 95% confidence interval (CI) 2.03–5.29] and poorer OS [hazard ratio (HR) 3.18, 95% CI 2.08–4.84]. In the propensity score matched cohort, blood transfusion was similarly associated with higher median POD 3 CRP [130 (IQR 93–196 mg/L) vs. 113 (IQR 66–173 mg/L); p = 0.046], lower median POD 3 albumin [24 (IQR 20–26 g/L) vs. 26 (IQR 24–30 g/L); p < 0.001], more postoperative complications (OR 2.91, 95% CI 1.36–6.20) and poorer OS (HR 2.38, 95% CI 0.99–5.73). Conclusions: Perioperative blood transfusion was associated with postoperative inflammation, complications, and poorer survival in patients undergoing colorectal cancer surgery, with and without propensity score techniques

The epidemiology and aetiology of diarrhoeal disease in infancy in southern Vietnam: a birth cohort study.

OBJECTIVES: Previous studies indicate a high burden of diarrhoeal disease in Vietnamese children, however longitudinal community-based data on burden and aetiology are limited. The findings from a large, prospective cohort study of diarrhoeal disease in infants in southern Vietnam are presented herein. METHODS: Infants were enrolled at birth in urban Ho Chi Minh City and a semi-rural district in southern Vietnam, and followed for 12 months (n=6706). Diarrhoeal illness episodes were identified through clinic-based passive surveillance, hospital admissions, and self-reports. RESULTS: The minimum incidence of diarrhoeal illness in the first year of life was 271/1000 infant-years of observation for the whole cohort. Rotavirus was the most commonly detected pathogen (50% of positive samples), followed by norovirus (24%), Campylobacter (20%), Salmonella (18%), and Shigella (16%). Repeat infections were identified in 9% of infants infected with rotavirus, norovirus, Shigella, or Campylobacter, and 13% of those with Salmonella infections. CONCLUSIONS: The minimum incidence of diarrhoeal disease in infants in both urban and semi-rural settings in southern Vietnam was quantified prospectively. A large proportion of laboratory-diagnosed disease was caused by rotavirus and norovirus. These data highlight the unmet need for a rotavirus vaccine in Vietnam and provide evidence of the previously unrecognized burden of norovirus in infants

BOB CAT: a Large-Scale Review and Delphi Consensus for Management of Barrett’s Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia

OBJECTIVES: Barrett’s esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD). METHODS: We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations. RESULTS: In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients. CONCLUSIONS: In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research

Application and optimisation of the Comparison on Extreme Laboratory Tests (CERT) algorithm for detection of adverse drug reactions: Transferability across national boundaries.

PURPOSE: The Singapore regulatory agency for health products (Health Sciences Authority), in performing active surveillance of medicines and their potential harms, is open to new methods to achieve this goal. Laboratory tests are a potential source of data for this purpose. We have examined the performance of the Comparison on Extreme Laboratory Tests (CERT) algorithm, developed by Ajou University, Korea, as a potential tool for adverse drug reaction detection based on the electronic medical records of the Singapore health care system. METHODS: We implemented the original CERT algorithm, comparing extreme laboratory results pre- and post-drug exposure, and 5 variations thereof using 4.5 years of National University Hospital (NUH) electronic medical record data (31 869 588 laboratory tests, 6 699 591 drug dispensings from 272 328 hospitalizations). We investigated 6 drugs from the original CERT paper and an additional 47 drugs. We benchmarked results against a reference standard that we created from UpToDate 2015. RESULTS: The original CERT algorithm applied to all 53 drugs and 44 laboratory abnormalities yielded a positive predictive value (PPV) and sensitivity of 50.3% and 54.1%, respectively. By raising the minimum number of cases for each drug-laboratory abnormality pair from 2 to 400, the PPV and sensitivity increased to 53.9% and 67.2%, respectively. This post hoc variation, named CERT400, performed particularly well for drug-induced hepatic and renal toxicities. DISCUSSION: We have demonstrated that the CERT algorithm can be applied across national boundaries. One modification (CERT400) was able to identify adverse drug reaction signals from laboratory data with reasonable PPV and sensitivity, which indicates potential utility as a supplementary pharmacovigilance tool

Associations with Intraocular Pressure in a Large Cohort: Results from the UK Biobank

Purpose: To describe the associations of physical and demographic factors with Goldmann-correlated intraocular pressure (IOPg) and corneal-compensated intraocular pressure (IOPcc) in a British cohort. Design: Cross-sectional study within the UK Biobank, a large-scale multisite cohort study in the United Kingdom. Participants: We included 110 573 participants from the UK Biobank with intraocular pressure (IOP) measurements available. Their mean age was 57 years (range, 40–69 years); 54% were women, and 90% were white. Methods: Participants had 1 IOP measurement made on each eye using the Ocular Response Analyzer noncontact tonometer. Linear regression models were used to assess the associations of IOP with physical and demographic factors. Main Outcome Measures: The IOPg and IOPcc. Results: The mean IOPg was 15.72 mmHg (95% confidence interval [CI], 15.70–15.74 mmHg), and the mean IOPcc was 15.95 mmHg (15.92–15.97 mmHg). After adjusting for covariates, IOPg and IOPcc were both significantly associated with older age, male sex, higher systolic blood pressure (SBP), faster heart rate, greater myopia, self-reported glaucoma, and colder season (all P < 0.001). The strongest determinants of both IOPg and IOPcc were SBP (partial R2: IOPg 2.30%, IOPcc 2.26%), followed by refractive error (IOPg 0.60%, IOPcc 1.04%). The following variables had different directions of association with IOPg and IOPcc: height (−0.77 mmHg/m IOPg; 1.03 mmHg/m IOPcc), smoking (0.19 mmHg IOPg, −0.35 mmHg IOPcc), self-reported diabetes (0.41 mmHg IOPg, −0.05 mmHg IOPcc), and black ethnicity (−0.80 mmHg IOPg, 0.77 mmHg IOPcc). This suggests that height, smoking, diabetes, and ethnicity are related to corneal biomechanical properties. The increase in both IOPg and IOPcc with age was greatest among those of mixed ethnicities, followed by blacks and whites. The same set of covariates explained 7.4% of the variability of IOPcc but only 5.3% of the variability of IOPg. Conclusions: This analysis of associations with IOP in a large cohort demonstrated that some variables clearly have different associations with IOPg and IOPcc, and that these 2 measurements may reflect different biological characteristics