Stratifying management of rheumatic disease for pregnancy and breastfeeding

The management of inflammatory rheumatic diseases during pregnancy and breastfeeding has undergone considerable change in the past few years. Modern therapeutics, including biologic and targeted synthetic DMARDs, have enabled substantial improvements in the control of rheumatic diseases, resulting in more patients with severe disease considering pregnancy. Therefore, management of disease for these patients needs to be discussed with clinicians before, during and after pregnancy and patients need to know what complications they might experience before they become pregnant. This Review summarizes the effects pregnancy has on various rheumatic diseases and the effects these diseases have on pregnancy, as well as providing advice regarding the alteration and monitoring of therapy before, during and after pregnancy

A review of different sawing and drying techniques used in processing small-diameter logs.

The importance of small diameter logs in the sawmilling sector in the South East Asian region cannot be underplayed, as plantation-grown fast growing tree species is the main source of wood raw material for the rapidly expanding wood products industry in the region. The aim of this study was therefore to highlight the different sawing and drying techniques used in the processing of small-diameter logs from the fast growing forest plantations. A significant difference in processing yields and also the costs of the different techniques are obvious and the industry is poised to take advantage of the benefits provided by the saw-dry-rip (SDR) method of processing small-diameter logs. As opposed to the conventional live-sawing method widely used in hardwood sawing in the South East Asian region, the saw-dry-rip (SDR) method offers a more viable option to process the small-diameter logs, with significant reductions in rejects, while improving the overall yield. The overall economic benefits gained through the adoption of this technique warrants serious consideration by the sawmilling sector throughout the region

The BILAG2004-Pregnancy index is reliable for assessment of disease activity in pregnant SLE patients

Objective. To assess the inter-rater reliability of the BILAG2004-Pregnancy index for assessment of SLE disease activity in pregnancy. Methods. Pregnant SLE patients were recruited from four centres and assessed separately by two raters/physicians in routine clinical practice. Disease activity was determined using the BILAG2004-Pregnancy index. Reliability was assessed using level of agreement, κ-statistics and analysis of disagreement. Major disagreement was defined as a score difference of A and C/D/E or B and D/E between the two raters, and minor disagreement was a score difference of A and B or B and C between raters. Results. A total of 30 patients (63.3% Caucasian, 13.3% Afro-Caribbean, 16.7% South Asian) were recruited. The majority of patients had low-level disease activity according to the local rater’s assessment, and there was no grade A activity, with grade B activity present in the following systems: mucocutaneous (nine patients), musculoskeletal (two patients), cardiorespiratory (one patient) and renal (one patient). The distribution of disease activity was similar to the external rater’s assessment. Good levels of agreement (>70%) were achieved in all systems. κ-statistics were not appropriate for use in the gastrointestinal, ophthalmic, constitutional and neuropsychiatric systems, as there was minimal variation between patients but good levels of agreement otherwise. There were three major disagreements (0.1 per patient, all differences between B and D/E) and five minor disagreements (0.17 per patient). Conclusion. The BILAG2004-Pregnancy index is reliable for assessment of disease activity in pregnant SLE patients

Birmingham SLE cohort: outcomes of a large inception cohort followed for up to 21 years.

OBJECTIVE: The aim of this study was to describe the outcomes and predictors for development of damage in a large inception cohort of SLE patients. METHODS: This was a prospective longitudinal study of a cohort of SLE patients. SLE patients were included if they were recruited within 3 years of achieving the fourth ACR criterion for SLE. Data were collected on disease activity, damage and treatment. Information on death was provided by the Office for National Statistics. The censoring date for analysis was 31 December 2010. A standardized mortality ratio was calculated. Poisson regression was used to determine the incidence rate for damage accrual. Multistate Markov modelling was used to determine predictors for development of damage. RESULTS: There were 382 patients (92.4% females, 51.6% Caucasian, 22% South Asian, 20.7% Afro-Caribbean) with 12 072 assessments and total follow-up of 2958 patient-years. There were 300 items of damage (in 143 patients) and 37 deaths. The overall standardized mortality ratio was 2.0 (95% CI 1.5, 2.8) and the most common causes of death were infection (37.8%), cardiovascular (27%) and malignancy (13.5%). The predictors for damage accrual were higher prior damage, older age at diagnosis, active disease, systemic corticosteroid exposure and CYC exposure. Patients were more likely to develop new damage earlier in their disease than later. Ethnicity was not predictive of damage accrual or death in this cohort. CONCLUSION: SLE patients have premature mortality. Active disease, corticosteroid exposure and CYC exposure were independently associated with the development of damage. Damage accrual is more likely to occur in early disease

The BILAG2004-Pregnancy Index is a valid disease activity outcome measure for pregnant SLE patients

OBJECTIVES: This study was to determine whether the BILAG2004-Pregnancy Index (BILAG2004-P) has construct/criterion validity and is sensitive to change. METHODS: This was an observational multicentre study that recruited pregnant SLE patients. Data were collected on disease activity [using the BILAG2004-P and Physician Global Assessment (PGA)], investigations and therapy at each assessment. The overall BILAG2004-P score as determined by the highest score achieved by any system was used in the analysis. Cross-sectional analysis was used for construct and criterion validity. The comparison was with C3, C4 and anti-dsDNA for construct validity, while it was with change in therapy and PGA in criterion validity. Sensitivity to change was assessed by determining the relationship between the change in BILAG2004-P and the change in therapy between two consecutive visits. RESULTS: A total of 97 patients with 112 pregnancies were recruited. There were 610 assessments available for construct/criterion validity analysis (98.2% of pregnancies had more than one assessment) and 497 observations for sensitivity to change analysis. Increasing BILAG2004-P scores were associated with low C3. The active BILAG2004-P score (grade A or B) was associated with an increase in therapy and the PGA of active disease. There was an increasing likelihood of higher overall scores with an increase in therapy and the PGA of active disease. In the sensitivity to change analysis, an increase in the BILAG2004-P score was associated with an increase in therapy and inversely associated with a decrease in therapy. A decrease in the BILAG2004-P score was associated with a decrease in therapy and inversely associated with an increase in therapy. CONCLUSION: The BILAG2004-P has criterion validity and is sensitive to change

Zerumbone-loaded nanostructured lipid carrier induces apoptosis in human colorectal adenocarcinoma (Caco2) cell line

The incorporation of zerumbone (Zer) into nanostructured lipid carrier (NLC) is hypothesized to increase the efficacy of the drug. Nanostructured lipid carrier has sustained-drug release characteristics and is able to improve the solubility and bioavailability of the lipophilic drug. In this study, the anti-cancer effect of Zer was tested on human colorectal adenocarcinoma (Caco-2) cell line. The effect of Zer, zerumbone-loaded nanostructured lipid carrier (Zer-NLC) and NLC on the Caco-2 cell viability were determined using the MTT assay. The treatment concentration ranges from 0 to 120 μM at four different time intervals (i.e., 0 h, 24 hrs, 48 hrs and 72 hrs) were evaluated. At 24 hrs, the half-growth inhibitory concentration (GI50) of Zer-NLC (i.e., 4.25 μM) is lower than that of Zer (i.e., 23.75 μM). However, Zer outperformed the Zer-NLC at the subsequent time points. Similar trend was observed in other parameters including the cytostatic concentration (CC) and half-lethal concentration 50 (LC50). Phase contrast imaging and AO/PI fluorescence staining were performed at the CC and LC50 values. The morphological changes and the apoptosis features could be seen in cells treated with Zer and Zer-NLC while cells treated with NLC showed minor morphological changes. The cells treated with Zer-NLC demonstrated a slightly slower progression of apoptosis, which could be due to the controlled release of Zer from the NLC matrix. It was concluded that the incorporation of Zer into NLC did not compromise the potency and efficacy of the drug

Identifikacija bioaktivnih proteina gljive Ophiocordyceps sinensis i određivanje njihovog antioksidacijskog i citotoksičnog učinka pomoću shotgun analize proteoma

Research background. Ophiocordyceps sinensis, a highly valued medicinal fungus, is close to extinction due to overexploitation. Successful cultivation of O. sinensis fruiting body (OCS02®) shows that the cultivar has a promising nutritional value and numerous bioactive compounds. Antioxidant and antiproliferative properties and biologically active proteins of the OCS02® are investigated for possible development into nutraceuticals. Experimental approach. The chemical composition of the OCS02® cold water extract was determined, and the antioxidant activities were examined using ferric reducing, DPPH• and O2•- scavenging assays. Tetrazolium dye (MTT) cytotoxic assay was performed to assess the antiproliferative activity of the extract. Bioactive proteins in the active fraction of the extract were identified using liquid chromatography (LC) and tandem-mass spectrometry (MS/MS). Results and conclusions. The OCS02® extract exhibited strong O2•- scavenging (expressed as Trolox equivalents (18.4±1.1) mol/g) and potent cytotoxic activities against adenocarcinomic human alveolar basal epithelial (A549) cells (IC50=(58.2±6.8) µg/mL). High molecular mass polysaccharides, proteins and protein-polysaccharide complexes could have contributed to the antioxidant and cytotoxic selectivity of the OCS02®. LC-MS/MS analysis identified several potential cytotoxic proteases and an oxalate decarboxylase protein which may exhibit protection effects on kidneys. Novelty and scientific contribution. The findings demonstrate the potential of OCS02® to be developed into functional food due to its promising superoxide anion radical scavenging capacity, cytotoxic effect and presence of biopharmaceutically active proteins.Pozadina istraživanja. Vrlo cijenjena medicinska gljiva Ophiocordyceps sinensis je na rubu izumiranja zbog njezine prekomjerne eksploatacije. Uspješnim uzgojem plodišta gljive O. sinensis (OCS02®) potvrđeno je da taj kultivar ima obećavajuća hranjiva svojstva te sadržava brojne bioaktivne spojeve. Ispitana su njegova antioksidacijska i antiproliferacijska svojstva te sastav biološki aktivnih proteina, s ciljem mogućeg razvoja nutraceutika. Eksperimentalni pristup. Utvrđen je kemijski sastav ekstrakta gljive u hladnoj vodi, a antioksidacijska je aktivnost ispitana pomoću FRAP metode te metodama uklanjanja DPPH˙ i O2 radikala. Citotoksičnost odnosno antiproliferacijska aktivnost ekstrakta ispitana je testom na osnovi tetrazolija (MTT test). Bioaktivni proteini su identificirani u aktivnoj frakciji ekstrakta pomoću tekućinske kromatografije i tandemske spektrometrije masa. Rezultati i zaključci. Ekstrakt gljive OCS02® imao je izrazito jako svojstvo uklanjanja superoksid radikala (izraženo u ekvivalentima Troloxa (18,4±1,1) mol/g) i snažan citotoksični učinak (IC50=(58,2±6,8) µg/mL) na humane epitelne stanice adenokarcinoma pluća (A549). Moguće je da polisaharidi, proteini i kompleksi proteina s polisaharidima velike molekularne mase pridonose antioksidacijskoj i citotoksičnoj selektivnosti gljive OCS02®. Tekućinskom kromatografijom i tandemskom spektrometrijom masa identificirano je nekoliko potencijalno citotoksičnih proteaza te protein oksalat dekarboksilaza koji bi mogli imati zaštitni učinak na bubrege. Novina i znanstveni doprinos. Dobiveni rezultati pokazuju da se gljiva OCS02® može upotrijebiti u proizvodnji funkcionalne hrane zbog njezine obećavajuće sposobnosti uklanjanja superoksidnih aniona, citotoksičnog učinka te prisutnosti biofarmaceutski aktivnih proteina

The BILAG-2004 systems tally-a novel way of representing the BILAG-2004 index scores longitudinally

Objective. This was an exploratory analysis to develop a new way of representing BILAG-2004 system scores longitudinally that would be clinically meaningful and easier to analyse in comparison with multiple categorical variables. Methods. Data from a multicentre longitudinal study of SLE patients (the BILAG-2004 index and therapy collected at every visit) were used. External responsiveness analysis of the index suggested the possibility of using counts of systems with specified transitions in scores as a basis to analyse the system scores. Exploratory analyses with multinomial logistic regression were used to examine the appropriateness of this new method of analysing BILAG-2004 system scores. Receiver operating characteristic (ROC) curve analysis was used to assess the performance of this approach. Results. There were 1414 observations from 347 patients. A novel method was devised based on counts of systems with defined transitions in score (BILAG-2004 systems tally, BST). It has six components (systems with major deterioration, systems with minor deterioration, systems with persistent significant activity, systems with major improvement, systems with minor improvement and systems with persistent minimal or no activity). This was further simplified (simplified BST, sBST) into three components (systems with active/worsening disease, systems with improving disease and systems with persistent minimal or no activity). Both versions had expected associations with change in therapy. ROC curve analyses demonstrated that both versions had similar good performance characteristics (areas under the curve >0.80) in predicting increase in therapy. Conclusion. The BST and sBST provide alternative approaches to representing BILAG-2004 disease activity longitudinally. Further validation of their use is required

Numerical scoring for the BILAG-2004 index

Objective. To develop an additive numerical scoring scheme for the BILAG-2004 index

Sensitivity to Change (Responsiveness) and Minimal Important Differences of the LupusQoL in patients with Systemic Lupus Erythematosus

Objective: The LupusQoL is a reliable and valid health-related quality of life (HRQoL) measure for adults with systemic lupus erythematosus (SLE). This study evaluates the responsiveness and minimal important differences (MID) for the eight LupusQoL domains. Methods: Patients experiencing a flare were recruited from nine UK centres. At each of the ten monthly visits, HRQoL (LupusQoL, SF-36), global rating of change (GRC) and disease activity (DA) using the BILAG-2004 index were assessed. The responsiveness of the LupusQoL and the SF-36 was evaluated primarily when patients reported an improvement or deterioration on the GRC scale and, secondly, with changes in physician-reported DA. MIDs were estimated as mean changes when minimal change was reported on the GRC scale. Results: 101 patients were recruited. For all LupusQoL domains, mean HRQoL worsened when patients reported deterioration and improved when patients reported an improvement in GRC; SF-36 domains showed comparable responsiveness. Improvement in some domains of the LupusQoL/SF-36 was observed with a decrease in DA but when DA worsened, there was no significant change. LupusQoL MID estimates for deterioration ranged from -2.4 to -8.7 and for improvement, 3.5 to 7.3; for the SF-36, -2.0 to -11.1, and 2.8 to 10.9 respectively. Conclusion: All LupusQoL domains are sensitive to change with patient-reported deterioration or improvement in health status. For DA, some LupusQoL domains showed responsiveness when there was improvement but none for deterioration. LupusQoL items were derived from SLE patients and provide the advantage of disease-specific domains, important to them, not captured by the SF-36