A retrospective record review of tuberculous infections in rheumatoid arthritis patients on biologics in Malaysia.

INTRODUCTION: The aim of this study was to analyse the clinical characteristics of patients with rheumatoid arthritis receiving biologics therapy and investigate the association between types of biologics and tuberculosis (TB) infections in 13 tertiary hospitals in Malaysia. MATERIALS AND METHODS: This was a retrospective study that included all RA patients receiving biologics therapy in 13 tertiary hospitals in Malaysia from January 2008 to December 2018. RESULTS: We had 735 RA patients who received biologics therapy. Twenty-one of the 735 patients were diagnosed with TB infection after treatment with biologics. The calculated prevalence of TB infection in RA patients treated with biologics was 2.9% (29 per 1000 patients). Four groups of biologics were used in our patient cohort: monoclonal TNF inhibitors, etanercept, tocilizumab, and rituximab, with monoclonal TNF inhibitors being the most commonly used biologic. The median duration of biologics therapy before the diagnosis of TB was 8 months. 75% of patients had at least one co-morbidity and all patients had at least one ongoing cDMARD therapy at the time of TB diagnosis. More than half of the patients were on steroid therapy with an average prednisolone dose of 5 mg daily. CONCLUSION: Although the study population and data were limited, this study illustrates the spectrum of TB infections in RA patients receiving biologics and potential risk factors associated with biologics therapy in Malaysia.

Compression of hard core-soft shell nanoparticles at liquid-liquid interfaces: influence of the shell thickness.

Soft hydrogel particles show a rich structural and mechanical behaviour compared to hard particles, both in bulk and when confined in two dimensions at a fluid interface. Moreover, encapsulation into hydrogel shells makes it possible to transfer the tunability of soft steric interactions to hard nanoparticle cores, which bear interest for applications, e.g. in terms of optical, magnetic and reinforcement properties. In this work, we investigate the microstructures formed by hard core-soft shell particles at liquid-liquid interfaces upon compression. We produced model particles with the same silica core and systematically varied the shell-to-core ratio by synthesising shells with three different thicknesses. These particles were spread at an oil-water interface in a Langmuir-Blodgett trough and continuously transferred onto a solid support during compression. The transferred microstructures were analysed by atomic force and scanning electron microscopy. Quantitative image analysis provided information on the particle packing density, the inter-particle distance, and the degree of order of the monolayers. We discovered several essential differences compared to purely soft hydrogel particles, which shed light on the role played by the hard cores in the assembly and compression of these composite monolayers.

A new classification system and taxonomic synopsis for Malpighiaceae (Malpighiales, Rosids) based on molecular phylogenetics, morphology, palynology, and chemistry.

Malpighiaceae has undergone unprecedented changes in its traditional classification in the past two decades due to several phylogenetic studies shedding light on the non-monophyly of all subfamilies and most tribes and genera. Even though morphological characters were used to reconstruct the last molecular generic phylogeny of Malpighiaceae, a new classification system has never been proposed for this family. Based on a comprehensive review of the last twenty years of published studies for this family, we propose a new classification system and provide a taxonomic synopsis for Malpighiaceae based on molecular phylogenetics, morphology, palynology, and chemistry as a baseline for the systematics, conservation, and taxonomy of this family worldwide. Malpighiaceae currently comprises two subfamilies (Byrsonimoideae and Malpighioideae), 12 tribes ( Acmanthereae, Acridocarpeaetrib. nov., Barnebyeaetrib. nov., Bunchosieaetrib. nov., Byrsonimeae, Galphimieae, Gaudichaudieae, Hiptageae, Hiraeeae, Malpighieae, Mcvaughieaetrib. nov., and Ptilochaeteaetrib. nov.), 72 genera (incl. Mamedeagen. nov.), and 1,499 accepted species (715 of which are currently under some kind of extinction threat). We present identification keys for all subfamilies, tribes, and genera, a full morphological description for the proposed new genus, the re-circumscription of ten genera alongside the needed new combinations, the proposition of several new synonyms, the typification of several names, and notes on the taxonomy, distribution, conservation, and ecology up to the genus rank. Morphological plates are also provided to illustrate the immense diversity of morphological traits used in the new classification and synopsis.

Electrically driven nanopillars for THz quantum cascade lasers.

In this work we present a rapid and parallel process for the fabrication of large scale arrays of electrically driven nanopillars for THz quantum cascade active media. We demonstrate electrical injection of pillars of 200 nm diameter and 2 µm height, over a surface of 1 mm(2). THz electroluminescence from the nanopillars is reported. This result is a promising step toward the realization of zero-dimensional structure for terahertz quantum cascade lasers.

Evolution of connective glands reveals a new synapomorphy for Malpighiaceae and the hidden potential of staminal glands for Malpighiales systematics.

Connective glands are important morphological characters for the taxonomy of some genera of Malpighiaceae, with few recent studies having just elucidated these glands' anatomical and ecological functions. In order to test the systematic relevance of connective glands to the currently accepted phylogenetic informal clades of Malpighiaceae, we characterised the anatomy and/or histochemistry of two-thirds of Malpighiaceae genera and ten species from nine families of Malpighiales to test: 1. Do connective glands occur in the flowers of all informal clades of Malpighiaceae?; and 2. Are they taxonomically relevant to characterise those clades? We sampled 25 genera and 26 species of Malpighiaceae, processing their anthers using traditional anatomical methods and characterising their glands using light microscopy and SEM imaging. Selected species were subjected to histochemical tests, and an additional 21 genera and 33 species of Malpighiaceae and nine families (ten species) of Malpighiales were included in our sampling from the literature. Three anatomical characters were scored, coded and mapped using Maximum Likelihood methods onto the molecular phylogeny of Malpighiaceae. All sampled species of Malpighiaceae showed connective glands characterised as epidermal or trichomal elaiophores. Our character-mapping analyses recovered connective elaiophores as a new synapomorphy for Malpighiaceae. Different types of epidermal or trichomal elaiophores were recovered as homoplasies for the Christianella and Banisteriopsis clades and the genera Byrsonima, Camarea and Cottsia. Our analyses also recovered the glands' place of insertion in the stamen and the exudate type as potential new synapomorphies or homoplasies for the families of Malpighiales sampled. Our results propose the connective elaiophores as a new synapomorphy for Malpighiaceae and hypothesise the role that different staminal glands might play in the systematics of Malpighiales. Further comprehensive anatomical studies are still needed for the staminal glands of most families of this order to shed new light on the patterns recovered in our study.

Intermittent versus continuous chemotherapy in advanced colorectal cancer: a randomised 'GISCAD' trial.

BACKGROUND: In advanced colorectal cancer, chemotherapy is usually administered without pauses and until progression but patients can experience cumulative toxicity and cannot tolerate a heavy therapeutic charge. AIM: The aim of the present trial was to evaluate whether an intermittent chemotherapy with levo-leucovorin + 5-fluorouracil (5-FU) + irinotecan (CPT-11) was at least as effective as the same regimen given continuously, both administered until progression, in patients affected with advanced colorectal cancer and not previously exposed to chemotherapy for metastatic disease. PATIENTS, MATERIALS AND METHODS: A total of 337 patients from 27 institutions were randomised between levo-leucovorin, 100/mg/m(2) i.v. + 5-FU; 400 mg/m(2) i.v. bolus + 5-FU; 600 mg/m(2) 22-h continuous infusion, days 1 and 2 + CPT-11; 180 mg/m(2) day 1, administered every 2 weeks 2 months on and 2 months off (arm A) and the same regimen administered continuously (arm B), until progression in both arms. The main end point was overall survival (OS), the secondary progression-free survival (PFS) and toxicity. RESULTS: At a median follow-up of 41 months, OS was 18 months in arm A and 17 months in arm B [hazard ratio (HR), 0.88]. Also PFS was comparable in the two groups (6 months in both, with HR, 1.03), and even grades 3-4 toxicity (mainly myelosuppression, fever and diarrhoea) was similar. Second-line oxaliplatin-based treatment was administered in a similar percentage (66%) in the two arms. The median chemotherapy-free period (drug holiday) in arm A was 3.5 months. CONCLUSION: Reducing the charge of therapy in this population did not diminish the efficacy of treatment. Further studies with this strategy, including biologicals, are warranted.

Shear banding and flow-concentration coupling in colloidal glasses.

We report experiments on hard-sphere colloidal glasses that show a type of shear banding hitherto unobserved in soft glasses. We present a scenario that relates this to an instability due to shear-concentration coupling, a mechanism previously thought unimportant in these materials. Below a characteristic shear rate γ(c) we observe increasingly nonlinear and localized velocity profiles. We attribute this to very slight concentration gradients in the unstable flow regime. A simple model accounts for both the observed increase of γ(c) with concentration, and the fluctuations in the flow.

Super-resolution microscopy on single particles at fluid interfaces reveals their wetting properties and interfacial deformations.

Solid particles adsorbed at fluid interfaces are crucial for the mechanical stability of Pickering emulsions. The key parameter which determines the kinetic and thermodynamic properties of these colloids is the particle contact angle, θ. Several methods have recently been developed to measure the contact angle of individual particles adsorbed at liquid-liquid interfaces, as morphological and chemical heterogeneities at the particle surface can significantly affect θ. However, none of these techniques enables the simultaneous visualization of the nanoparticles and the reconstruction of the fluid interface to which they are adsorbed, in situ. To tackle this challenge, we utilize a newly developed super-resolution microscopy method, called iPAINT, which exploits non-covalent and continuous labelling of interfaces with photo-activatable fluorescent probes. Herewith, we resolve with nanometer accuracy both the position of individual nanoparticles at a water-octanol interface and the location of the interface itself. First, we determine single particle contact angles for both hydrophobic and hydrophilic spherical colloids. These experiments reveal a non-negligible dependence of θ on particle size, from which we infer an effective line tension, τ. Next, we image elliptical particles at a water-decane interface, showing that the corresponding interfacial deformations can be clearly captured by iPAINT microscopy.

Exploring the colloid-to-polymer transition for ultra-low crosslinked microgels from three to two dimensions.

Microgels are solvent-swollen nano- and microparticles that show prevalent colloidal-like behavior despite their polymeric nature. Here we study ultra-low crosslinked poly(N-isopropylacrylamide) microgels (ULC), which can behave like colloids or flexible polymers depending on dimensionality, compression or other external stimuli. Small-angle neutron scattering shows that the structure of the ULC microgels in bulk aqueous solution is characterized by a density profile that decays smoothly from the center to a fuzzy surface. Their phase behavior and rheological properties are those of soft colloids. However, when these microgels are confined at an oil-water interface, their behavior resembles that of flexible macromolecules. Once monolayers of ultra-low crosslinked microgels are compressed, deposited on solid substrate and studied with atomic-force microscopy, a concentration-dependent topography is observed. Depending on the compression, these microgels can behave as flexible polymers, covering the substrate with a uniform film, or as colloidal microgels leading to a monolayer of particles.

IGEV regimen and a fixed dose of lenograstim: an effective mobilization regimen in pretreated Hodgkin's lymphoma patients.

We explored the efficacy of the IGEV regimen (ifosfamide, gemcitabine, vinorelbine and prednisone) combined with a fixed dose of lenograstim (263 mug/day) to mobilize peripheral blood stem cells (PBSCs) in 90 Hodgkin's lymphoma patients. The median total CD34+ cells/mul peak, colony-forming units granulocyte-macrophage and white blood cells for all individual collection sets were 85/mul, 12 x 10(4)/kg and 20 700/mul, respectively. An adequate number of CD34+ cells (more than 3 x 10(6) or 6 x 10(6) CD34+ cells/kg depending on whether single or tandem high-dose chemotherapy was used) were collected in 89 out of 90 (98.7%) mobilized patients, whereas the only failure reached 2.3 x 10(6) CD34+ cells/kg. The median CD34+ cell collections were 11 x 10(6)/kg (range 2.3-39 x 10(6)/kg) and 10 x 10(6)/kg (range 6-22.0 x 10(6)/kg) with a median of 1 and 2 leukaphereses for patients eligible for single high-dose treatment and for candidates for tandem transplant, respectively. Target yields were reached in 71.43 and 49.09% and additionally in 17.14 and 43.64% of cases after the first and second apheresis procedures, respectively. Hematological and non-hematological side effects were acceptable, and no toxic deaths occurred. Thirty-four patients received a single and 47 received tandem transplantation with rapid engraftment. These results confirm that the IGEV regimen with lenograstim support can be used successfully and safely to mobilize PBSCs.

EXPERIENCE WITH miniplate osteosynthesis in THE MANAGEMENT OF mandibular fractures IN NORTHWEST NIGERIA.

BACKGROUND: Fractures of the mandible are the commonest facial fractures and various treatment modalities exist like wire osteosynthesis and the use of miniplates and screw with most of the industrially developed world leaning towards the use of miniplates in the treatment of these fractures. The use has however been limited in developing countries (including Nigeria) mostly due to the cost of the plates and screws. AIM AND OBJECTIVES: To identify the versatility of miniplates in the treatment of mandibular fractures at a tertiary care centre in a developing country. METHODS: All Subjects aged 16 years and above in whom mandibular fractures were diagnosed were recruited over a two year period. Patients were treated under general anesthesia using either the miniplates and screws or wire osteosynthesis while some patients had both miniplates and maxillo-maxillary fixation. RESULTS: A total of 94 patients were recruited for the study of which 89.4% were males while the age group 16 to 25 years constituted the majority. Though 29.8% of the study population was involved in business, only 9.6 % were professional motorcyclists. Motorcycle-related road traffic crashes constituted the commonest aetiologic agent with 41.5%, while combination fractures were the commonest fracture types seen in 54.3% of the study participants. Of the 94 patients, 77.7% had treatment of mandibular fractures by open reduction and immobilization with mini plates, while 7.4% had mini plates with Maxillo-maxillary fixation and 14.9% had wire osteosynthesis only. The site of fracture was significantly associated with the treatment modality (p= 0.02). CONCLUSION: This study showed that the choice of fixation appliances in mandibular fractures was influenced by the number of fractures and the multiplicity of fracture sites. Miniplates offered functionally stable fixation with minimum complications.

Enhanced photoelectrochemical water oxidation via atomic layer deposition of TiO2 on fluorine-doped tin oxide nanoparticle films.

TiO2 is an exemplary semiconductor anode material for photoelectrochemical (PEC) water-splitting electrodes due to its functionality, long-term stability in corrosive environments, nontoxicity, and low cost. In this study, TiO2 photoanodes with enhanced photocurrent density were synthesized by atomic layer deposition (ALD) of TiO2 onto a porous, transparent, and conductive fluorine-doped tin oxide nanoparticle (nanoFTO) scaffold fabricated by solution processing. The simplicity and disordered nature of the nanoFTO nanostructure combined with the ultrathin conformal ALD TiO2 coatings offers advantages including decoupling charge carrier diffusion length from optical penetration depth, increased photon absorption probability through scattering, complimentary photon absorption, and favorable interfaces for charge separation and transfer across the various junctions. We examine the effects of porosity of the nanoFTO scaffold and thickness of the TiO2 coating on PEC performance and achieve an optimal photocurrent of 0.7 mA cm(-2) at 0 V vs. Ag/AgCl under 100 mW cm(-2) AM 1.5 G irradiation in a 1 M KOH aqueous electrolyte. Furthermore, the fundamental mechanisms behind the improvements are characterized via cyclic voltammetry, incident photon-to-current efficiency, transient photocurrent spectroscopy, and electrochemical impedance spectroscopy and are contrasted with those of single crystal rutile TiO2 nanowires. The strategies employed in this work highlight the opportunities inherent to these types of heteronanostructures, where the lessons may be applied to improve the PEC conversion efficiencies of other promising semiconductors, such as hematite (α-Fe2O3) and other materials more sensitive to visible light.

Correction: Enhanced photoelectrochemical water oxidation via atomic layer deposition of TiO2 on fluorine-doped tin oxide nanoparticle films.

Correction for 'Enhanced photoelectrochemical water oxidation via atomic layer deposition of TiO2 on fluorine-doped tin oxide nanoparticle films' by Isvar A. Cordova, et al., Nanoscale, 2015, 7, 8584-8592.

DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) is an effective regimen for peripheral blood stem cell collection in multiple myeloma.

DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) has proved to be an effective salvage therapy for refractory-relapsed MM patients. Little is known, however, about its potential as mobilizing therapy. The aim of this study was to evaluate the efficacy of DCEP in mobilizing PBSC and to define its toxicity. Fifty-five MM patients received DCEP followed by G-CSF as part of high-dose programs including autologous transplantation. At the time of mobilization, 40 patients had previously received VAD only, and 15 alkylating agents. Mobilization was successful (minimum number of CD34(+) cells 2 x 10(6)/kg) in 48/55 patients (87%), and 41/55 patients (75%) collected >4 x 10(6)/kg CD34(+) cells. Of the seven patients who did not mobilize stem cells, five (71%) had been previously exposed to alkylating agents. The median number of CD34(+) cells harvested was 5.8 x 10(6)/kg (range 2.1-22.4). There was no treatment-related mortality. The side-effects of DCEP were always tolerable. No neutropenia <1000/microl nor thrombocytopenia <50,000/microl were observed. No patient required transfusion as a consequence of therapy, or hospitalization for septic complications. In conclusion, DCEP, in addition to its demonstrated anti-tumor activity, is an effective regimen for mobilizing peripheral blood progenitor cells in myeloma patients, with little or no side-effects. These properties render DCEP a useful regimen for the debulking and mobilization phase of high-dose programs for multiple myeloma.

Cisplatin-vinorelbine combination chemotherapy in locally advanced non-small cell lung cancer.

AIM: The North Milan Group presents the results of a phase II study on a cisplatin-vinorelbine combination schedule in the treatment of locally advanced non-small cell lung cancer to evaluate its activity and tolerability. METHODS: Seventy-six consecutive patients entered the study. Patients' characteristics were the following: males/females 69/7; median age, 61.4 years (range, 40-73); ECOG performance status, 0-1; 17 stage IIIa and 59 stage IIIb. There were 49 squamous cell carcinomas, 20 adenocarcinomas, and 7 large cell carcinomas. All patients had not been previously treated and showed measureable disease. Treatment consisted of vinorelbine, 25 mg/m2 on days 1 and 8, plus cisplatin, 80 mg/m2 on day 1, administered intravenously every 21 days for three standard courses. RESULTS: Seventy-four patients were evaluable for response. Objective responses were documented in 42/74 patients with an overall response rate (CR+PR) of 56.7%; 18/74 patients (24.3%) showed stable disease and the remaining 14/74 (18.9%) went into progression. Twelve patients (16.2%) were suitable for a subsequent surgery. The median duration of response was 13.3 months. Survival time ranged from 4 to 36 months; it was 14.6 months for PR patients, 8.6 months for NC and 5 months for PD. Mean survival time is presently 12.85 months (SE, 1.2 months). Toxicity evaluated on 222 cycles administered was acceptable, and it was necessary to use G-CSF or delay the treatment because of severe leukopenia in only a few cases. CONCLUSIONS: The regimen is active and safe: the slight survival increase is likely due to the small amenability to surgery achieved (16.2%). However, our results are fully comparable to others obtained with vinorelbine in two/three drug combination chemotherapy regimens.

Impaired efficacy of selective LDL-apheresis in primary biliary cirrhosis.

Low-density lipoprotein apheresis (LDL-apheresis) was done with either cascade filtration (DF) or dextran sulfate cellulose adsorption (DSC) in a patient with primary biliary cirrhosis who developed severe dyslipidemia associated with cholestasis and accumulation of lipoprotein-X (LP-X). The extracorporeal treatment was initially performed weekly, and resulted in a sharp drop in total cholesterol from 1038 to 430 mg/dl. During the next four months the patient was treated every 10-15 days, and pre-apheresis cholesterol levels were maintained between 438 and 505 mg/dl, until an orthotopic liver transplantation was successfully performed. With semi-selective DF a mean 47.1% of total cholesterol was removed per procedure compared to 30.0% with DSC, although the volume of treated plasma was 38.0 vs 49.9 ml/kg body weight. The changes in plasma cholesterol levels during DSC and DF showed that the kinetics of cholesterol removal were similar with both techniques, but the efficacy differed; DF removed both LDL and LP-X from plasma, whereas DSC selectively lowered the LDL content. Cascade filtration may therefore be considered as a first-choice treatment for patients with LP-X accumulation due to cholestasis.

[Observations on bone mineral metabolism in natural and surgical menopause. Role of synthetic salmon calcitonin and calcium on bone turnover]. / Osservazioni sul metabolismo minerale osseo nella menopausa naturale e chirurgica. Ruolo della calcitonina sintetica di salmone e del calcio sul turnover osseo.

Loss of bone mass is a process which generally becomes manifest in women during the fourth decade of life and is considerably accelerated following the onset of menopause, especially if this in surgically induced. Bone mineral metabolism was studied in 104 women, subdivided into the following groups: group 1: 33 women with normal menstrual cycles; group 2: 30 women in pre-menopause; group 3: 38 women who had undergone ovariectomy but had not received any osteotrope treatment; group 4: 33 ovariectomised women who had been treated immediately after surgery with calcium (1 g/die per os) in addition to synthetic salmon calcitonin nasal spray (100 IU on alternate days). Patients in groups 2-4 were analysed on entry into the study (time 0) and after 6 and 12 months of menopause (natural or surgical) using biochemical tests (alkaline phosphatase, calcium and phosphorus metabolism, PTH and osteocalcin) and by calculating bone mineral content (BMC) using a single photon ray performed at 3 cm and 8 cm from the styloid apophysis of the radius. The groups were matched for age, body mass index, dietary and sexual habits, geographic area. The results obtained can be summarised as follows: a) the concentrations of the main biochemical parameters were found to be normal and substantially similar between all groups at time 0; however, after 12 months increments relating to alkaline phosphatase and osteocalcin were significantly higher in ovariectomised women who did not receive treatment compared to ovariectomised patients treated with calcium + calcitonin, thus indicating a lower bone turnover in the latter group. b) BMC values, measured at the distal radius.

[Chronic alcoholism and arterial hypertension. Contribution to the comprehension of the phenomenon and practical implications]. / Etilismo cronico ed ipertensione arteriosa. Contributo alla comprensione del fenomeno ed implicazioni pratiche.

Alcohol abuse is a frequent contributor to elevated blood pressure. 710 chronic alcoholics, aged 26-60 years, admitted for detoxification were studied. We compared hypertension prevalence in alcoholics with that in a similar group of non-alcoholics matched for age, sex, and miscellaneous diseases. The prevalence of hypertension was higher in heavy drinkers (11.4%) than in non drinker subjects (3.4%). Abstinence from alcohol during hospitalization was followed by normalization of hypertensive status in a high percentage of patients (70%). The majority of hypertensive alcoholics (75%) developed target organ damage ranging from retinopathy to hypertensive cardiomyopathy and renal lesion. In a 4.6 +/- 2.8 years follow-up study of 42 hypertensive alcoholic subjects, we observed that hypertension was 26% in those who abstained alcohol ingestion versus 84% in those who remained actively alcoholics. Four patients died of liver failure and two of stroke.