Synthesis of temporomandibular disorders management intervention outcomes for development of core outcome sets: A systematic review.

INTRODUCTION: The selection of appropriate outcomes in clinical trials and systematic reviews is a crucial factor in determining the results that are useful, reliable, and relevant for both patients and healthcare professionals. Clinicians and researchers have been encouraged to develop and apply core outcome sets (COS) to minimise the discrepancy between studies. AIM: This systematic review is the first phase of the COS development project for clinical trials in temporomandibular disorders (COS-TMD). It aims to identify and synthesise the outcomes used in the randomised controlled trials (RCT) that evaluated the effectiveness of interventions used in TMD management. MATERIALS AND METHODS: An electronic search was performed in several databases: MEDLINE (via PubMed), Scopus, Web of Science, Cochrane Library and EMBASE. The eligibility criteria comprised RCT that applied any intervention to treat temporomandibular joint disorders or masticatory muscle disorders. The identified outcomes were categorised according to domains of the Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT). RESULTS: The electronic search resulted in 1606 studies. After removing duplicates and applying the eligibility criteria, 106 RCT were included. A total of 43 studies evaluated masticatory muscle disorders, 27 evaluated temporomandibular joint disorders, and 36 analysed mixed TMD. CONCLUSIONS: The evaluation showed significant variability in the types of outcomes and their measurement instruments. In addition, some domains such as physical and emotional functioning, participant ratings of global improvement and adverse events have been neglected when determining the effectiveness of treatments for TMD.

The Bradyrhizobium Sp. LmicA16 Type VI Secretion System Is Required for Efficient Nodulation of Lupinus Spp.

Many bacteria of the genus Bradyrhizobium are capable of inducing nodules in legumes. In this work, the importance of a type VI secretion system (T6SS) in a symbiotic strain of the genus Bradyrhizobium is described. T6SS of Bradyrhizobium sp. LmicA16 (A16) is necessary for efficient nodulation with Lupinus micranthus and Lupinus angustifolius. A mutant in the gene vgrG, coding for a component of the T6SS nanostructure, induced less nodules and smaller plants than the wild-type (wt) strain and was less competitive when co-inoculated with the wt strain. A16 T6SS genes are organized in a 26-kb DNA region in two divergent gene clusters of nine genes each. One of these genes codes for a protein (Tsb1) of unknown function but containing a methyltransferase domain. A tsb1 mutant showed an intermediate symbiotic phenotype regarding vgrG mutant and higher mucoidity than the wt strain in free-living conditions. T6SS promoter fusions to the lacZ reporter indicate expression in nodules but not in free-living cells grown in different media and conditions. The analysis of nodule structure revealed that the level of nodule colonization was significantly reduced in the mutants with respect to the wt strain.

PCR screening reveals abundance of bovicin-like bacteriocins among ruminal Streptococcus spp. isolated from beef and dairy cattle.

AIMS: To investigate the inhibitory activity and the distribution of biosynthetic genes encoding bovicin-like bacteriocins among ruminal Streptococcus isolated from beef and dairy cattle. METHODS AND RESULTS: Most isolates were classified as Streptococcus equinus and Streptococcus lutetiensis based on 16S rRNA sequencing. The antimicrobial activity of 150 ruminal streptococci isolated from beef and dairy cattle were tested by deferred inhibition assays and their genetic diversity was characterized by BOX-PCR. The frequency of biosynthetic genes associated with the biosynthesis of bovicin-like bacteriocins (bovicin HC5 and bovicin 255) was investigated by PCR screening. Approximately 33% of the ruminal streptococci isolated from Nellore heifers showed inhibitory activity in vitro with the majority harbouring genes for bacteriocin biosynthesis. In contrast, streptococci from Holstein cows showed limited inhibitory activity and a lower frequency of bacteriocin biosynthetic genes. CONCLUSIONS: Streptococcus from the rumen of beef and dairy cattle exhibit remarkable differences in inhibitory activity and distribution of genes associated with the biosynthesis of prototypical bovicins (bovicin HC5 and bovicin 255). SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings demonstrate that bovicin HC5 is distributed among ruminal streptococci from different breeds of cattle. The high degree of conservation of the bovicin HC5 structural gene among strains of ruminal streptococci suggests that random genetic drift is not a dominant force in the evolution of this bacteriocin.

A single administration of human adipose tissue-derived mesenchymal stromal cells (MSC) induces durable and sustained long-term regulation of inflammatory response in experimental colitis.

Current therapies for inflammatory bowel diseases (IBD) are aimed at controlling the exacerbated response in the gut, but no treatment is fully effective for many refractory patients. Mesenchymal stromal cells (MSC) are multi-potent cells with regulatory immunosuppressive activity that may control inflammatory diseases. In this study, we investigated the short- and especially the long-term protective effects of MSC on experimental colitis. We show that MSC elicited protection to acute intestinal inflammation with gain of weight, improvement in the clinical disease score and expressive reduction in the mortality rate of treated mice. MSC changed the population of neutrophils, eosinophils and augmented the frequency of CD4 T lymphocytes in the gut-draining lymph nodes, together with reduced accumulation of these cells in the colon intraepithelial compartment. Interestingly, there were increased levels of programmed death 1 (PD-1) and glucocorticoid-induced tumour necrosis factor receptor family-related receptor (GITR) in the spleen regulatory T cells of mice that received MSC treatment, which also presented a reversal in the pattern of immune response in the gut, with diminished inflammatory, T helper type 1 (Th1) and Th17 profile, in contrast to augmented Th2 responses. Most strikingly, this balanced response elicited by a single administration of MSC during the acute colitis persisted long-term, with restored goblet cells, eosinophils and maintenance of elevated gut interleukin (IL)-4, besides increased CD4+ CD25+ PD-1+ cells in the spleen and reduced Th17 response in mesenteric lymph nodes (MLN) of treated mice on day 60. Taken together, our findings provided a significant contribution to translational immunology by pointing human adipose tissue-derived MSC as a novel therapeutic approach with long-term beneficial regulatory effects in experimental colitis.

Molecular modelling and quantum biochemistry computations of a naturally occurring bioremediation enzyme: Alkane hydroxylase from Pseudomonas putida P1.

Many species of bacteria involved in degradation of n-alkanes have an important constitutional metabolic enzyme, the alkane hydroxylase called AlkB, specialized in the conversion of hydrocarbons molecules that can be used as carbon and/or energy source. This enzyme plays an important role in the microbial degradation of oil, chlorinated hydrocarbons, fuel additives, and many other compounds. A number of these enzymes has been biochemically characterized in detail because the potential of alkane hydroxylases to catalyse high added-value reactions is widely recognized. Nevertheless, the industrial and process bioremediation application of them is restricted, owing to their complex biochemistry, challenging process requirements, and the limited number of their three-dimensional structures. Furthermore, AlkB has great potential as biocatalysts for selective transformation of a wide range of chemically inert unreactive alkanes into reactive chemical precursors that can be used as tools for bioremediation and bioprocesses. Aiming to understand the possible ways the AlkB enzyme Pseudomonas putida P1 interacts with octane, octanol and 1-octyne, we consider its suitable biochemical structure taking into account a 3-D homology modelling. Besides, by using a quantum chemistry computational model based on the density functional theory (DFT), we determine possible protein-substrate interaction regions measured by means of its binding energy simulated throughout the Molecular Fractionation with Conjugated Caps (MFCC) approach.

Portugal and Angola: similarities and differences in Toxoplasma gondii seroprevalence and risk factors in pregnant women.

In this study we determined the presence of IgM/IgG antibodies to Toxoplasma gondii in sera of 155 and 300 pregnant women from Lisbon (Portugal) and Luanda (Angola), respectively, and evaluated the potential risk factors associated with this infection. DNA detection was performed by PCR assays targeting T. gondii regions (RE/B1). Overall, 21·9% (10·9% IgG, 10·9% IgG/IgM) of the Lisbon women and 27·3% (23·7%, IgG, 2% IgM, 1·7% IgG/IgM) of the Luanda women had antibodies to T. gondii. Single variable and binary logistic regression analyses were conducted. Based on the latter, contacts with cats (family/friends), and having more than two births were identified as risk factors for Toxoplasma infection in Lisbon women. In Luanda, the risk factors for T. gondii infection suggested by the single variable analysis (outdoor contact with cats and consumption of pasteurized milk/dairy products) were not confirmed by binary logistic regression. This study shows original data from Angola, and updated data from Portugal in the study of infection by T. gondii in pregnant women, indicating that the prevalence of anti-Toxoplasma antibodies is high enough to alert the government health authorities and implement appropriate measures to control this infection.

Multicentre study highlighting clinical relevance of new high-throughput methodologies in molecular epidemiology of Pneumocystis jirovecii pneumonia.

Pneumocystis jirovecii causes severe interstitial pneumonia (PcP) in immunosuppressed patients. This multicentre study assessed the distribution frequencies of epidemiologically relevant genetic markers of P. jirovecii in different geographic populations from Portugal, the USA, Spain, Cuba and Mozambique, and the relationship between the molecular data and the geographical and clinical information, based on a multifactorial approach. The high-throughput typing strategy for P. jirovecii characterization consisted of DNA pooling using quantitative real-time PCR followed by multiplex-PCR/single base extension. The frequencies of relevant P. jirovecii single nucleotide polymorphisms (mt85, SOD110, SOD215, DHFR312, DHPS165 and DHPS171) encoded at four loci were estimated in ten DNA pooled samples representing a total of 182 individual samples. Putative multilocus genotypes of P. jirovecii were shown to be clustered due to geographic differences but were also dependent on clinical characteristics of the populations studied. The haplotype DHFR312T/SOD110C/SOD215T was associated with severe AIDS-related PcP and high P. jirovecii burdens. The frequencies of this genetic variant of P. jirovecii were significantly higher in patients with AIDS-related PcP from Portugal and the USA than in the colonized patients from Portugal, and Spain, and children infected with P. jirovecii from Cuba or Mozambique, highlighting the importance of this haplotype, apparently associated with the severity of the disease and specific clinical groups. Patients from the USA and Mozambique showed higher rates of DHPS mutants, which may suggest the circulation of P. jirovecii organisms potentially related with trimethoprim-sulfamethoxazole resistance in those geographical regions. This report assessed the worldwide distribution of P. jirovecii haplotypes and their epidemiological impact in distinct geographic and clinical populations.

Trends, seasonality and forecasts of pulmonary tuberculosis in Portugal.

SETTING: Tuberculosis (TB) is a global public health concern. Surveillance programmes present invaluable epidemiological information regarding its temporal evolution, particularly for pulmonary tuberculosis (PTB), the most common form of TB and the one that presents the greatest challenge in public health. OBJECTIVES: To characterise, model and predict monthly incidence rates for PTB in Portugal disaggregated by high/low-incidence areas, sex and age groups. DESIGN: PTB monthly incidence rates were estimated based on PTB cases diagnosed in 2000-2010, disaggregated by population and geographic characteristics. Seasonal-trend LOESS (STL) decomposition was employed to model trend and seasonality. Seasonal autoregressive integrated moving average (SARIMA) models were fit to characterise series behaviour and forecast PTB monthly incidence rates. RESULTS: Overall, the time series showed a downward trend in and seasonality of PTB diagnosis, with a peak in March and a trough in December. The mean seasonal amplitude was consistently higher in high-incidence areas, in males and in adults aged 25-54 years. SARIMA models were found to adequately fit and forecast the time series, thus predicting trend and seasonal persistence. CONCLUSIONS: STL and SARIMA findings concurred and were accurate. Endemic PTB seems to be slowly declining and case diagnosis is likely seasonal, which can be expected to persist if past conditions continue.

(1-3)-beta-D-glucan in association with lactate dehydrogenase as biomarkers of Pneumocystis pneumonia (PcP) in HIV-infected patients.

Pneumocystis pneumonia (PcP) is a major HIV-related illness caused by Pneumocystis jirovecii. Definitive diagnosis of PcP requires microscopic detection of P. jirovecii in pulmonary specimens. The objective of this study was to evaluate the usefulness of two serum markers in the diagnosis of PcP. Serum levels of (1-3)-beta-d-glucan (BG) and lactate dehydrogenase (LDH) were investigated in 100 HIV-positive adult patients and 50 healthy blood donors. PcP cases were confirmed using indirect immunofluorescence with monoclonal anti-Pneumocystis antibodies and nested-PCR to amplify the large subunit mitochondrial rRNA gene of P. jirovecii in pulmonary specimens. BG and LDH levels in serum were measured using quantitative microplate-based assays. BG and LDH positive sera were statistically associated with PcP cases (P ≤ 0.001). Sensitivity, specificity, positive/negative predictive values (PPV/NPV), and positive/negative likelihood ratios (PLR/NLR) were 91.3 %, 61.3 %, 85.1 %, 79.2 %, 2.359, and 0.142, respectively, for the BG kit assay, and 91.3 %, 35.5 %, 75.9 %, 64.7 %, 1.415 and 0.245, respectively, for the LDH test. Serologic markers levels combined with the clinical diagnostic criteria for PcP were evaluated for their usefulness in diagnosis of PcP. The most promising cutoff levels for diagnosis of PcP were determined to be 400 pg/ml of BG and 350 U/l of LDH, which combined with clinical data presented 92.8 % sensitivity, 83.9 % specificity, 92.8 % PPV, 83.9 % NPV, 5.764 PLR and 0.086 NLR (P < 0.001). This study confirmed that BG is a reliable indicator for detecting P. jirovecii infection. The combination between BG/LDH levels and clinical data is a promising alternative approach for PcP diagnosis.

Age-period-cohort effects in the incidence of hip fractures: political and economic events are coincident with changes in risk.

UNLABELLED: An age-period cohort model was fitted to analyse time effects on hip fracture incidence rates by sex (Portugal, 2000-2008). Rates increased exponentially with age (age effect). Incidence rates decreased after 2004 for women and were random for men (period effect). New but comprehensive fluctuations in risk were coincident with major political/economic changes (cohort effect). INTRODUCTION: Healthcare improvements have allowed prevention but have also increased life expectancy, resulting in more people being at risk. Our aim was to analyse the separate effects of age, period and cohort on incidence rates by sex in Portugal, 2000-2008. METHODS: From the National Hospital Discharge Register, we selected admissions (aged ≥ 49 years) with hip fractures (ICD9-CM, codes 820.x) caused by low/moderate trauma (falls from standing height or less), readmissions and bone cancer cases. We calculated person-years at risk using population data from Statistics Portugal. To identify period and cohort effects for all ages, we used an age-period-cohort model (1-year intervals) followed by generalised additive models with a negative binomial distribution of the observed incidence rates of hip fractures. RESULTS: There were 77,083 hospital admissions (77.4 % women). Incidence rates increased exponentially with age for both sexes (age effect). Incidence rates fell after 2004 for women and were random for men (period effect). There was a general cohort effect similar in both sexes; risk of hip fracture altered from an increasing trend for those born before 1930 to a decreasing trend following that year. Risk alterations (not statistically significant) coincident with major political and economic change in the history of Portugal were observed around birth cohorts 1920 (stable-increasing), 1940 (decreasing-increasing) and 1950 (increasing-decreasing only among women). CONCLUSIONS: Hip fracture risk was higher for those born during major economically/politically unstable periods. Although bone quality reflects lifetime exposure, conditions at birth may determine future risk for hip fractures.

Pneumocystis jirovecii multilocus genotyping in pooled DNA samples: a new approach for clinical and epidemiological studies.

Specific single-nucleotide polymorphisms (SNPs) are recognized as important DNA sequence variations influencing the pathogenesis of Pneumocystis jirovecii and the clinical outcome of Pneumocystis pneumonia, which is a major worldwide cause of illness among immunocompromised patients. Genotyping platforms for pooled DNA samples are promising methodologies for genetic characterization of infectious organisms. We have developed a new typing strategy for P. jirovecii, which consisted of DNA pools prepared according to clinical data (HIV diagnosis, microscopic and molecular detection of P. jirovecii, parasite burden, clinical diagnosis and follow-up of infection) from individual samples using quantitative real-time PCR followed by multiplex-PCR/single base extension (MPCR/SBE). The frequencies of multiple P. jirovecii SNPs (DHFR312, mt85, SOD215 and SOD110) encoded at three distinct loci, the dihydrofolate reductase (DHFR), the mitochondrial large-subunit rRNA (mtLSU rRNA) and the superoxide dismutase (SOD) loci, were estimated in seven DNA pooled samples, representing a total of 100 individual samples. The studied SNPs were confirmed to be associated with distinct clinical parameters of infection such as parasite burden and follow-up. The MPCR/SBE-DNA pooling methodology, described in the present study, was demonstrated to be a useful high-throughput procedure for large-scale P. jirovecii SNPs screening and a powerful tool for evaluation of clinically relevant SNPs potentially related to parasite burden, clinical diagnosis and follow-up of P. jirovecii infection. In further studies, the candidate SNPs mt85, SOD215 and SOD110 may be used as molecular markers in association with MPCR/SBE-DNA pooling to generate useful information for understanding the patterns and causes of Pneumocystis pneumonia.

Clinical relevance of multiple single-nucleotide polymorphisms in Pneumocystis jirovecii Pneumonia: development of a multiplex PCR-single-base-extension methodology.

Pneumocystis jirovecii pneumonia (PcP) is a major cause of respiratory illness in patients with AIDS. The identification of multiple single-nucleotide polymorphisms (SNPs) at three distinct P. jirovecii loci encoding dihydrofolate reductase (DHFR), mitochondrial large-subunit rRNA (mtLSU rRNA), and superoxide dismutase (SOD) was achieved using multiplex-PCR (MPCR) followed by direct sequencing and two single-base extension (SBE) techniques. Four SNPs (DHFR312, mt85, SOD215, and SOD110), correlated previously with parameters of disease, were amplified and genotyped simultaneously. The concordance of results between the standard sequencing technique (direct sequencing) and SBE analysis was 96.9% for the acrylamide gel electrophoresis and 98.4% for the capillary electrophoresis. The cross-genetic analysis established several statistical associations among the SNPs studied: mt85C-SOD110T, SOD110T-SOD215C, and SOD110C-SOD215T. These results were confirmed by cluster analysis. Data showed that among the isolates with low to moderate parasite burden, the highest percentages of DHFR312C, mt85C, SOD110T, and SOD215C were detected, whereas for high parasite burden cases the highest frequencies were observed among isolates with DHFR312T, mt85T, SOD110C, and SOD215T. The polymorphisms studied were shown to be suitable genetic targets potentially correlated with PcP clinical data that can be used as predictors of outcome in further studies to help clinical decision-making in the management of PcP. The MPCR/SBE protocol described for the first time in the present study was shown to be a rapid, highly accurate method for genotyping P. jirovecii SNPs encoded by different loci that could be used for epidemiological studies and as an additional procedure for the prognostic classification and diagnosis of PcP.

Numerical response of a helminth community in the course of a multi-annual abundance cycle of the water vole (Arvicola terrestris).

The impact of parasitism on population dynamics is determined in part by the numerical responses of parasites during population fluctuations of their hosts. Vole populations fluctuate in multi-annual cycles allowing such responses to be studied over successive phases of population growth, abundance and decline. We investigate how a helminth community (5 nematode and 7 cestode species) evolved over a full 6-year Water Vole (Arvicola terrestris) population cycle. Brillouin and individual parasite species richness (IPSR) indices were used to measure the numerical response of the parasite community. We report a correlation between levels of parasite intensity and vole population cycle phases. Both indices were consistently higher during pre-decline and decline phases for male and female voles alike. The numerical response of the parasite community suggests that populations may be regulated by parasitism and that studies of this mechanism should allow both for the cyclic or non-cyclic character of the host populations and for the response of the broadest possible set of the local parasite community.

Prescription problems: clinical pharmacology and lawsuits.

Prescription errors are the second most frequent malpractice claim filed against physicians in the United States. Drug claims are also the second most expensive dispute that all physicians confront, and primary care physicians account for most of those claims. Family practitioners, internists, and other primary care physicians are the physicians who will benefit most from acquiring further knowledge of clinical pharmacology. Such knowledge will lead to a consistent approach to qualitative and quantitative decision making in the therapeutics of patient management. Knowledge of clinical pharmacology should allow practitioners to distinguish drug-related events from unpredictable changes in the course of the disease and should provide a diversified knowledge about objective therapeutics that will allow these clinicians to individualize therapy.

Iatrogenic hallux varus surgical procedure: a study of 14 cases.

Hallux varus occurs most frequently as a result of excessive surgical correction of musculoligamentous imbalance around the metatarsophalangeal (MTP) joint of the great toe (lateral release and medial capsuloligamentous tensioning). If untreated, the condition may lead to motion loss and degenerative arthritis. In this series, 14 cases of hallux varus were treated. Medial arthrolysis was done in each case. In five cases, reconstruction of the lateral ligament (with a 1.5-mm Ligapro suture), using a new technique, accompanied the medial release. Arthrodesis of the MTP was done in nine cases treated when there was already stiffness and arthrosis. According to a 100-point scoring system, the results were excellent in 56% and good in 44% of the MTP joint arthrodesis cases. Results were excellent in 100% of the mobilizing technique cases using Ligapro suture.

Medium-term results of 173 ligamentoplasties of the anterior cruciate ligament using the MacIntosh technique reinforced by the Kennedy ligament augmentation device (LAD).

This is a retrospective study of 173 cases of chronic laxity of the knee, surgically treated between May 1985 and December 1988 using the MacIntosh technique (quadriceps-plasty) reinforced with the Kennedy ligament augmentation device (LAD). It involved 171 operations, 113 men and 58 women aged between 15 and 49 years (average 26 years), the majority of whom were active in sports both at competition (51 cases) and at recreational level (119 cases). There were 101 lesions of the medial meniscus (58.4%) and 94 lesions of the lateral meniscus (54.4%); only 41 knees had no meniscal lesion (23.6%). The results at medium term (between 4 and 8 years follow-up) were based on 107 cases (61.8%). The tolerance of the reinforcement was excellent as there were no instances of either acute or chronic synovitis in this series. The anatomical results evaluated using the Lachmann test (maximum manual Lachmann) showed no differential in 24 cases (22.8%), a differential of between 0 and 2 mm in 54 cases (50.5%), of between 2 and 4 mm in 20 cases (19%) and of > 4 mm in 9 cases (8.7%). The functional results evaluated using the Arpège CLAS system showed 83% of results to be satisfactory (score > 23). The radiological results showed that 63 knees (58.9%) had no subclinical or clinical signs of medial or lateral femorotibial osteoarthritis. In total, with an average follow-up of > 5 years (4-8 years), it was found that the MacIntosh quadriceps-plasty reinforced with the Kennedy LAD was not accompanied by any iatrogenic disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Prilocaine: an old anesthetic agent and a new ophthalmic procedure.

We present a new local anesthetic technique for ophthalmic surgery that reduces the risks associated with retrobulbar and peribulbar anesthesia. This method uses topical proparacaine plus 1.5 mL of prilocaine (3%) with felypressin injected into the subconjunctival (sub-Tenon's) space. Of 5210 consecutive adult patients in whom the technique was used, all demonstrated adequate analgesia. Sixty-three (1.2%) of the eyes required supplemental analgesia, provided by a single injection of prilocaine (0.5 mL). Ecchymosis and subconjunctival hemorrhage developed in 63 (1.2%) of the eyes. There were no instances of ptosis.