Classifying Polypharmacy According to Pharmacotherapeutic and Clinical Risks in Older Adults: A Latent Class Analysis in Quebec, Canada.

INTRODUCTION: The simplistic definition of polypharmacy, often designated as the concomitant use of five medications or more, does not distinguish appropriate from inappropriate polypharmacy. Classifying polypharmacy according to varying levels of health risk would help optimise medication use. OBJECTIVE: We aimed to characterise different types of polypharmacy among older adults and evaluate their association with mortality and institutionalisation. METHODS: Using healthcare databases from the Quebec Integrated Chronic Disease Surveillance System, we selected a community-based random sample of the population ≥ 66 years old covered by the public drug plan. Categorical indicators used to describe polypharmacy included number of medications, potentially inappropriate medications (PIMs), drug-drug interactions, enhanced surveillance medications, complex route of administration medications, anticholinergic cognitive burden (ACB) score and use of blister cards. We used a latent class analysis to subdivide participants into distinct groups of polypharmacy. Their association with 3-year mortality and institutionalisation was assessed with adjusted Cox models. RESULTS: In total, 93,516 individuals were included. A four-class model was selected with groups described as (1) no polypharmacy (46% of our sample), (2) high-medium number of medications, low risk (33%), (3) medium number of medications, PIM use with or without high ACB score (8%) and (4) hyperpolypharmacy, complex use, high risk (13%). Using the class without polypharmacy as the reference, all polypharmacy classes were associated with 3-year mortality and institutionalisation, with the most complex/inappropriate classes denoting the highest risk (hazard ratio [HR] [95% confidence interval]: class 3, 70-year-old point estimate for mortality 1.52 [1.30-1.78] and institutionalisation 1.86 [1.52-2.29]; class 4, 70-year-old point estimate for mortality 2.74 [2.44-3.08] and institutionalisation 3.11 [2.60-3.70]). CONCLUSIONS: We distinguished three types of polypharmacy with varying pharmacotherapeutic and clinical appropriateness. Our results highlight the value of looking beyond the number of medications to assess polypharmacy.

Monitoring of sterigmatocystin biosynthesis using RT-qPCR in airborne Aspergillus species of the series Versicolores.

Aspergilli series Versicolores have been shown to be explanatory variables for different symptoms like coughing and dizziness experienced by residents of mold-damaged homes. Among these species, eight are particularly recurrent in bioaerosols: Aspergillus amoenus, A. creber, A. fructus, A. jensenii, A. protuberus, A. puulaauensis, A. sydowii and A. tabacinus. In order to monitor the biosynthesis of sterigmatocystin (a mycotoxin associated with a risk of cancer development) and the development of these molds, we developed an RT-qPCR tool by targeting the aflR and rho1 genes. A total of 30 fungal isolates representing these eight species were included. For each of them, sterigmatocystin was quantified by UPLC-HRMS and (1 â†’ 3)-ß-D-glucan by visible spectrophotometry using Endosafe®-PTS™-Glucan Cartridges. After validation of our method by RT-qPCR, the direct assay was compared to the amount of aflR and rho1 cDNA. The sterigmatocystin and aflR assays showed a significant correlation between these two approaches (p < 0.0001), demonstrated for the first time the production of sterigmatocystin by A. tabacinus and suggested the ability of A. sydowii to synthesize sterigmatocystin. Assays conducted on (1 â†’ 3)-ß-D-glucan and rho1 did not show a correlation, supporting the multiplicity of functions performed in fungal cells by the RHO1 GTPase. The proposed tool could allow monitoring of sterigmatocystin biosynthesis by Aspergillus of the series Versicolores under different culture and climatic conditions.

In-house tooth-supported guide for the injection of botulinum toxin into the lateral pterygoid muscle using Blue Sky Plan software: A technical note.

Hyperactivity of the lateral pterygoid muscle (LPM) is one of the theories postulated to explain anterior disc displacement, which can result in difficulty in jaw opening, jaw protrusion, or jaw-deviation dystonias and interferes with mastication, speech, and swallowing. Injection of botulinum toxin of the LPM is considered a conservative therapeutic modality for this condition. The LPM is a deep facial structure and several techniques have been described that use magnetic resonance imaging, arthroscopic, or electromyographic guidance to perform intramuscular botulinum toxin injection safely this to prevent incorrect injection or complications, such arterial bleeding. This study provided a described step-by-step description of the computer-aided design and manufacturing procedure for the fabrication of an in-house guide to simplify the method of botulinum toxin injection in the LPM and ensure accuracy and safety in medical office.

Factors associated with the growing-finishing performances of swine herds: an exploratory study on serological and herd level indicators.

BACKGROUND: Growing and finishing performances of pigs strongly influence farm efficiency and profitability. The performances of the pigs rely on the herd health status and also on several non-infectious factors. Many recommendations for the improvement of the technical performances of a herd are based on the results of studies assessing the effect of one or a limited number of infections or environmental factors. Few studies investigated jointly the influence of both type of factors on swine herd performances. This work aimed at identifying infectious and non-infectious factors associated with the growing and finishing performances of 41 French swine herds. RESULTS: Two groups of herds were identified using a clustering analysis: a cluster of 24 herds with the highest technical performance values (mean average daily gain = 781.1 g/day +/- 26.3; mean feed conversion ratio = 2.5 kg/kg +/- 0.1; mean mortality rate = 4.1% +/- 0.9; and mean carcass slaughter weight = 121.2 kg +/- 5.2) and a cluster of 17 herds with the lowest performance values (mean average daily gain =715.8 g/day +/- 26.5; mean feed conversion ratio = 2.6 kg/kg +/- 0.1; mean mortality rate = 6.8% +/- 2.0; and mean carcass slaughter weight = 117.7 kg +/- 3.6). Multiple correspondence analysis was used to identify factors associated with the level of technical performance. Infection with the porcine reproductive and respiratory syndrome virus and the porcine circovirus type 2 were infectious factors associated with the cluster having the lowest performance values. This cluster also featured farrow-to-finish type herds, a short interval between successive batches of pigs (≤3 weeks) and mixing of pigs from different batches in the growing or/and finishing steps. Inconsistency between nursery and fattening building management was another factor associated with the low-performance cluster. The odds of a herd showing low growing-finishing performance was significantly increased when infected by PRRS virus in the growing-finishing steps (OR = 8.8, 95% confidence interval [95% CI]: 1.8-41.7) and belonging to a farrow-to-finish type herd (OR = 5.1, 95% CI = 1.1-23.8). CONCLUSIONS: Herd management and viral infections significantly influenced the performance levels of the swine herds included in this study.

Novel hyperthermia applicator system allows adaptive treatment planning: Preliminary clinical results in tumour-bearing animals.

Hyperthermia (HT) as an adjuvant to radiation therapy (RT) is a multimodality treatment method to enhance therapeutic efficacy in different tumours. High demands are placed on the hardware and treatment planning software to guarantee adequately planned and applied HT treatments. The aim of this prospective study was to determine the effectiveness and safety of the novel HT system in tumour-bearing dogs and cats in terms of local response and toxicity as well as to compare planned with actual achieved data during heating. A novel applicator with a flexible number of elements and integrated closed-loop temperature feedback control system, and a tool for patient-specific treatment planning were used in a combined thermoradiotherapy protocol. Good agreement between predictions from planning and clinical outcome was found in 7 of 8 cases. Effective HT treatments were planned and verified with the novel system and provided improved quality of life in all but 1 patient. This individualized treatment planning and controlled heat exposure allows adaptive, flexible and safe HT treatments in palliatively treated animal patients.

Catatonia with schizophrenia: From ECT to rTMS.

BACKGROUND: Electroconvulsive therapy is indicated in cases of catatonic schizophrenia following a failure of the challenge test with lorazepam or Zolpidem®. Some patients need maintenance treatment with ECT. Repetitive Transcranial Magnetic Stimulation (rTMS) and anodal Transcranial direct-current stimulation (tDCS) might be effective against catatonia. OBJECTIVE: Consider an alternative to ECT for a refractory patient. REVIEW: Twenty-one articles were identified mainly based on case reports series were found using search on Medline, Google Scholar, PsychInfo, CAIRNS. Key words were:"catatonia", and "rTMS", and more generally with"ECT","tDCS","Zolpidem®". At the end there were only six case reports with rTMS and three with tDCS. We discussed the alternative to ECT and follow up rTMS strategies illustrated by these case reports. FINDINGS: Patients mean age was 35; numbers of previous ECT vary from zero to 556; the most common motor threshold (MT) is 80%, with two patients with 110%, the most common treatment placement is L DLPFC. In one of them, ECT was the only acute-state or maintenance treatment effective in this patient, who underwent 556 ECT sessions over 20 years. High-frequency rTMS was considered as a possible alternative, given the potential adverse effects of chronic maintenance ECT in a patient with comorbid epilepsy. rTMS treatment was 3-4×/week and over time extended to once every two weeks. A persistent objective improvement in catatonia was observed on the Bush-Francis Catatonia Rating Scale. CONCLUSION: rTMS is helpful for acute and maintenance treatment for catatonic schizophrenia who both failed multiple pharmacologic interventions and had safety concerns with continuing maintenance ECT. Clinicians should consider rTMS as a potential treatment option for refractory catatonia.

Transfer of peanut allergy following lung transplantation: a case report.

This case study describes a patient who developed peanut allergy following lung transplantation. A 54-year-old woman underwent bilateral lung transplantation on June 2009 owing to severe chronic obstructive pulmonary disease. She had no history of food allergy before transplantation. The donor, however, was a 20-year-old man who was fatally injured during an automobile accident; he was allergic to peanuts. At 3 months after transplantation, the lung recipient presented with acute dyspnea and urticaria 15 minutes after consuming food containing peanut derivatives. Pre- and posttransplantation recipient blood samples analyzed for the presence of IgE antibodies specific for peanut allergens confirmed that the allergy had been passively transfered as a consequence of transplantation. Food allergy following solid organ transplantation is thought to be rare, mostly occurring in children. Two mechanisms may explain the observations described for the patient reported in this study: de novo development of peanut allergies after transplantation, or passive transfer of peanut allergies from a peanut-sensitized organ donor. This case report documenting pre- and posttransplantation IgE status in a lung transplantation case suggested that the allergic status of organ donors should be thoroughly assessed before transplantation, and potential allergy transfer risks must be discussed with the transplant team and the patient.

The influence of the reflective environment on the absorption of a human male exposed to representative base station antennas from 300 MHz to 5 GHz.

The environment is an important parameter when evaluating the exposure to radio-frequency electromagnetic fields. This study investigates numerically the variation on the whole-body and peak spatially averaged-specific absorption rate (SAR) in the heterogeneous virtual family male placed in front of a base station antenna in a reflective environment. The SAR values in a reflective environment are also compared to the values obtained when no environment is present (free space). The virtual family male has been placed at four distances (30 cm, 1 m, 3 m and 10 m) in front of six base station antennas (operating at 300 MHz, 450 MHz, 900 MHz, 2.1 GHz, 3.5 GHz and 5.0 GHz, respectively) and in three reflective environments (a perfectly conducting wall, a perfectly conducting ground and a perfectly conducting ground + wall). A total of 72 configurations are examined. The absorption in the heterogeneous body model is determined using the 3D electromagnetic (EM) finite-difference time-domain (FDTD) solver Semcad-X. For the larger simulations, requirements in terms of computer resources are reduced by using a generalized Huygens' box approach. It has been observed that the ratio of the SAR in the virtual family male in a reflective environment and the SAR in the virtual family male in the free-space environment ranged from -8.7 dB up to 8.0 dB. A worst-case reflective environment could not be determined. ICNIRP reference levels not always showed to be compliant with the basic restrictions.

Verification of cell irradiation dose deposition using a radiochromic film.

We describe a technique for the MTT assay that irradiates all cells at once by a combination of couch movement and a step-and-shoot irradiation technique on a linear accelerator with 6 MV and 18 MV photon beams. In two experimental setups, we obtained maximum to minimum dose ranges of 10 for the constant MU/bin (monitor units per bin) setup and 20 for the variable MU/bin technique. The irradiation technique described is dose rate independent and it can be used on any teletherapy irradiation machine. We also employed radiochromic film dosimetry to verify dose delivered in each of the wells within the dish. It is shown that for the lowest doses, relative dose variation within wells reaches a value of 6%. We also demonstrated that the radiochromic film positioned below the 96-well plate does not underestimate dose deposited within each compartment by more than 2% due to the vertical dose gradient.

Simulation of ozone depletion using ambient irradiance supplemented with UV lamps.

In studies of the biological effects of UV radiation, ozone depletion can be mimicked by performing the study under ambient conditions and adding radiation with UV-B lamps. We evaluated this methodology at three different locations along a latitudinal gradient: Rimouski (Canada), Ubatuba (Brazil) and Ushuaia (Argentina). Experiments of the effect of potential ozone depletion on marine ecosystems were carried out in large outdoor enclosures (mesocosms). In all locations we simulated irradiances corresponding to 60% ozone depletion, which may produce a 130-1900% increase in 305 nm irradiance at noon, depending on site and season. Supplementation with a fixed percentage of ambient irradiance provides a better simulation of irradiance increase due to ozone depletion than supplementation with a fixed irradiance value, particularly near sunrise and sunset or under cloudy skies. Calculations performed for Ushuaia showed that, on very cloudy days, supplementation by the square-wave method may produce unrealistic irradiances. Differences between the spectra of the calculated supplementing irradiance and the lamp for a given site and date will be a function of the time of day and may become more or less pronounced according to the biological weighting function of the effect under study.

[Cutaneous metastatic Crohn's disease]. / Manifestations métastatiques cutanées de la maladie de Crohn.

INTRODUCTION: Cutaneous metastatic Crohn's disease is a granulomatous inflammation of the skin that is noncontiguous to the gastrointestinal tract. CASE REPORT: A 42-year-old man with Crohn's disease is admitted for antibiotic resistant erysipela-like dermo-hypodermitis. The presence of granulomatous lesions on skin biopsy, the absence of any infectious agent identified despite extensive investigations and the dramatic improvement observed with corticosteroid eventually lead to the diagnosis of cutaneous metastatic Crohn's disease. CONCLUSION: During Crohn's disease, biopsy should be considered for every undiagnosed skin lesion as the characteristics of cutaneous metastatic Crohn's disease are not specific. The presence of a non caseous granulomatous dermal infiltration suggests the diagnosis and should make consider the initiation of corticosteroid and the discontinuation of others inappropriate therapeutics (i.e. surgical treatment, antibiotics).

Determination of equilibrium dissociation constants in fluorescence polarization.

A simple mathematical model (the FP K(d) model) is used to generate the dissociation equilibrium constant (K(d)) for G protein-coupled receptor-ligand binding measured using fluorescence polarization (FP) saturation curve analysis. The model generates data that may be analyzed by the method of Scatchard. The validity of the FP K(d) model is proven in six model systems in which the modeled K(d) values are within a factor of 5 of inhibitory equilibrium constant values obtained from radioligand competition assays.

Efficient gene transfer using reversibly cross-linked low molecular weight polyethylenimine.

Polyethylenimine (PEI) is a polycation with potential application as a nonviral vector for gene delivery. Here we show that after conjugation with homobifunctional amine reactive reducible cross-linking reagents, low molecular weight polyethylenimine efficiently mediates in vitro gene delivery to Chinese hamster ovary (CHO) cells. Two cross-linking reagents, dithiobis(succinimidylpropionate) (DSP) and dimethyl.3,3'-dithiobispropionimidate*2HCl (DTBP), were utilized based on their reactivity and chemical properties. Both reagents react with primary amines to form reducible cross-links; however, unlike DSP, the DTBP cross-linker maintains net polymer charge through amidine bond formation. PEI with a reported weight-average molecular weight (M(w)) of 800 Da was reacted with either DSP or DTBP at PEI primary amine:cross-link reactive group ratios of 1:1 and 2:1. The transfection efficiencies of the resulting cross-linked products were evaluated in CHO cells using a luciferase reporter gene under a cytomegalovirus (CMV) promoter. Our results show that cross-linked polymers mediate variable levels of transfection depending on the cross-linking reagent, the extent of conjugation, and the N/P ratio. In general, we found conjugate size to be proportional to gene transfer efficiency. Using gel retardation analysis, we also evaluate the capacity of the cross-linked polymers to condense plasmid DNA before and after reduction with 45 mM dithiothreitol (DTT). DTT mediated reduction of intra-cross-link disulfide bonds and inhibited condensation of DNA by conjugates cross-linked with DSP at a ratio of 1:1, but had little effect on the remaining polymers. Analogous intracellular reduction of transfection complexes by reduced glutathione could facilitate uncoupling of PEI from DNA to enhance gene expression.

Granulomatous pneumonitis following bone marrow transplantation.

We describe the rare occurrence of a granulomatous pneumonitis seen in a patient following allogeneic bone marrow transplantation. Interestingly sarcoidosis was diagnosed in the marrow donor less than a year after donating his bone marrow.

Quantitation of chemokines (MDC, TARC) expression in mucosa from Crohn's disease and ulcerative colitis.

Chemokines and their receptors are involved in the migration of different mononuclear cells. Among them macrophages-derived chemokines (MDC) and thymus-and activation regulated chemokine (TARC) belong to a new cluster of genes involve in Th2 lymphocytes homing. Cytokines appear to play a significant role in pathogenesis of inflammatory bowel diseases with an excessive Th1 response in chronic lesions of Crohn's disease (CD) and a Th2 pattern in both earlier mucosal CD lesions and in mucosa of ulcerative colitis (UC). Here we demonstrate that RNAm coding for MDC and TARC are expressed in mucosa from CD and UC patients. Using real-time fluorescent RT-PCR, MDC and TARC mRNA were increased in CD inflamed mucosa. Moreover MDC and TARC transcripts were increased in inflamed CD specimen compared to non-involved CD mucosa. These differences both discriminate CD from UC patients. Additionally, MDC protein was produced in isolated mononuclear cells from peripheral blood (PBMC) or mucosa (LPMC) from UC and CD patients: spontaneously, MDC production from PBMC was increased in CD compared to UC patients. MDC production from CD PBMC was also higher than that found in healthy controls. Together, these data indicate that MDC should be involved in the lymphocytes homing in mucosa from CD patients.

Novel C-terminus modifications of the Dmt-Tic motif: a new class of dipeptide analogues showing altered pharmacological profiles toward the opioid receptors.

The design, synthesis and pharmacological evaluation of a novel class of Dmt-Tic dipeptide analogues are described. These resulting analogues bearing different C-terminal functionalities were found to bind to the human delta receptor with high affinity. One specific class of dipeptides bearing urea/thiourea functionalities showed partial to full activation of the delta receptor. Several dipeptides also showed good binding affinities with full activation of the human kappa receptor, a novel property for those ligands.

[Crohn's disease complicated by multiple and recurrent aseptic splenic abscesses]. / Maladie de Crohn compliquée d'abcès aseptiques multiples et récidivants de la rate.

We report a case of multiple aseptic splenic abscesses occurring in a woman with Crohn's disease for three years. All microbiological samples were negative. The diagnosis was suspected on abdominal echography and CT scan and confirmed on histologic examination of the splenectomy specimen. The evolution was marked by recurrence of fever and inflammatory syndrome, associated to transitory morphological abnormalities of the accessory spleen. Aseptic splenic abscesses recurrence was suspected. This case allows us to consider aseptic splenic abscesses as an extra-intestinal manifestation and not as a splenic localisation of Crohn's disease.

The Responses of a Natural Bacterioplankton Community to Different Levels of Ultraviolet-B Radiation: A Food Web Perspective.

With the continuing increase of ultraviolet-B radiation (UVBR: 280-320 nm) fluxes toward the Earth's surface, there is concern regarding a possible negative impact on heterotrophic bacterioplankton. The effects of enhanced UVBR on a natural bacterioplankton community were studied during a 7-day experiment conducted in mesocosms (1500 L). Four light regimes were tested: natural light, 280 to 313 nm excluded UVBR, and two levels of UVBR enhancement. During the first 3 days of the experiment characterized by high inorganic nutrient concentrations (nitrates > 1 µmol L-1 and ammonium > 0.1 µmol L-l), UVBR had no effect on both bacterial abundances and activities. From day 4 to the end of the experiment, nitrate concentrations remained low (

Impact of a red-shifted dye label for high throughput fluorescence polarization assays of G protein-coupled receptors.

High throughput screening fluorescence polarization assays using G protein-coupled receptors (GPCRs) as targets have been compared using fluorescein and BODIPY TMR-labeled peptides. The red-shifted BODIPY TMR dye exhibits improved assay performance relative to fluorescein due to improvement in both ligand affinity to the GPCRs and assay precision brought about by the higher intensity probe. Furthermore, the red-shifted dye demonstrates an insensitivity to the effects of the highly colored compound tartrazine, which can produce false-negative results for assays conducted with fluorescein as a label.

A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9.

ACE2, the first known human homologue of angiotensin-converting enzyme (ACE), was identified from 5' sequencing of a human heart failure ventricle cDNA library. ACE2 has an apparent signal peptide, a single metalloprotease active site, and a transmembrane domain. The metalloprotease catalytic domains of ACE2 and ACE are 42% identical, and comparison of the genomic structures indicates that the two genes arose through duplication. In contrast to the more ubiquitous ACE, ACE2 transcripts are found only in heart, kidney, and testis of 23 human tissues examined. Immunohistochemistry shows ACE2 protein predominantly in the endothelium of coronary and intrarenal vessels and in renal tubular epithelium. Active ACE2 enzyme is secreted from transfected cells by cleavage N-terminal to the transmembrane domain. Recombinant ACE2 hydrolyzes the carboxy terminal leucine from angiotensin I to generate angiotensin 1-9, which is converted to smaller angiotensin peptides by ACE in vitro and by cardiomyocytes in culture. ACE2 can also cleave des-Arg bradykinin and neurotensin but not bradykinin or 15 other vasoactive and hormonal peptides tested. ACE2 is not inhibited by lisinopril or captopril. The organ- and cell-specific expression of ACE2 and its unique cleavage of key vasoactive peptides suggest an essential role for ACE2 in the local renin-angiotensin system of the heart and kidney. The full text of this article is available at http://www. circresaha.org.