Evolution of endurance during a multidisciplinary treatment of chronic low back pain and its influence of work capacity

Introduction: Low back pain is a common disorder touching up to 80% of the population, with redundancies of up to 70%. A small proportion would go on to develop chronic low back pain (LBP) with reduced work capacity and they would count for the majority of the costs. Up to day, a multi-disciplinary treatment program is one of the best approaches. In the program one of the mile-stones is restoration of function. The aim of this study was to follow patients, according to the endurance change after the program and its influence on workability during one year after inclusion in a such program. Method: Patients were following a multidisciplinary treatment for 3 weeks including physiotherapy, occupation measures combined with an educational program with behavioural and psychological interventions on an outpatient program. We studied the endurance with the help of the Bruce test, accomplished at the beginning and at the end of the program. On the other hand the patients filled out pain questionnaires and PACT score according their own impression on workability. Results: There were a clear relation between the increase in the cardiovascular endurance and the increased workability. Almost every patient presented an increase in the VO2 max, even though the workability did not follow. This increase were associated with a decrease in pain apprehension. Conclusion: A multidisciplinary treatment program, teaching the patients how to care with their pain and to accept it even if it persist is successful in lowering the global pain. If the program allows the patients to strengthen the endurance, the workability will increase in parallel. In this way the patients were able to reduce the consummation of medicaments and to increase the work capacity.

Influence of the host related factors in the development of the hepatosplenic form of schistosomiasis mansoni

The frequency of hepatosplenomegaly in endemic areas is not proportional to the fecal ova count. This may be explained by epidemiological genetic. The occurrence of two or more cases of schistosomal hepatosplenomegaly in nuclear family is much higher than expected. The concentration is higher among siblings than it is among mothers and children of further and children. It is not significant between father and mother. If the mother, instead of the father has hepatosplenic schistosomiasis the relative risk for the child to acquire hepatosplenomegaly is at least five times (the maternal affect). The inbreeding is highler in the hepatosplenic than in the hepatointestinal patients. In some areas in Brazil the hepatosplenic form of the schistosomiasis mansoni occurs with much higher frequency in whites than in blacks. After treatment, reversion of hepatosplenic schistosomiasis occurs more frequently in non-whithers. It seems that the resistance of blacks to the hepatosplenic form of schistosomiasis may be related to the glyoxalase system , perhaps associated to another genetic marker. The hepatosplenic schistosomiasis is less frequent in longilineal individuals. In some areas the hepatosplenic form of schistosomiasis is more frequent in A blood group of ABO sistem. The family heredograms do not suggest a single mendelian inheritance, but probably a multifactorial and possibility poligenic one.

The distribution of intestinal helminth infections in a rural village in Guatemala

Fecal egg count scores were used to investigate the distribution and abundance of intestinal helminths in the population of a rural village. Prevalences of the major helminths were 41% with Ascaris lumbricoides 60% with Trichuris trichiura and 50% with Necator americanus. All three parasites showed a highly aggregated distribution among hosts. Age/prevalence and age/intensity profiles were typical for both A. lumbricoides and T. trichiura with the highest worm burdens in the 50-10 year old children. For hookworm both prevalence and intensity curves were convex in shape with maximum infection levels in the 30-40 year old age class. Infected females had higher burdens of T. trichiura than infected males in all age classes of the population; there were no other effects of host gender. Analysis of associations between parasites within hosts revealed strong correlations between A. lumbricoides and T. lumbricoides and T. trichiura. Individuals with heavy infections of A. lumbricoides and T. trichiura showed highly significant aggregation within households. Associations between a variety of household features and heavy infections with A. lumbricoides and T. trichiura are described.

Improved virological outcome in White patients infected with HIV-1 non-B subtypes compared to subtype B.

BACKGROUND: Antiretroviral compounds have been predominantly studied in human immunodeficiency virus type 1 (HIV-1) subtype B, but only ~10% of infections worldwide are caused by this subtype. The analysis of the impact of different HIV subtypes on treatment outcome is important. METHODS: The effect of HIV-1 subtype B and non-B on the time to virological failure while taking combination antiretroviral therapy (cART) was analyzed. Other studies that have addressed this question were limited by the strong correlation between subtype and ethnicity. Our analysis was restricted to white patients from the Swiss HIV Cohort Study who started cART between 1996 and 2009. Cox regression models were performed; adjusted for age, sex, transmission category, first cART, baseline CD4 cell counts, and HIV RNA levels; and stratified for previous mono/dual nucleoside reverse-transcriptase inhibitor treatment. RESULTS: Included in our study were 4729 patients infected with subtype B and 539 with non-B subtypes. The most prevalent non-B subtypes were CRF02_AG (23.8%), A (23.4%), C (12.8%), and CRF01_AE (12.6%). The incidence of virological failure was higher in patients with subtype B (4.3 failures/100 person-years; 95% confidence interval [CI], 4.0-4.5]) compared with non-B (1.8 failures/100 person-years; 95% CI, 1.4-2.4). Cox regression models confirmed that patients infected with non-B subtypes had a lower risk of virological failure than those infected with subtype B (univariable hazard ratio [HR], 0.39 [95% CI, .30-.52; P < .001]; multivariable HR, 0.68 [95% CI, .51-.91; P = .009]). In particular, subtypes A and CRF02_AG revealed improved outcomes (multivariable HR, 0.54 [95% CI, .29-.98] and 0.39 [95% CI, .19-.79], respectively). CONCLUSIONS: Improved virological outcomes among patients infected with non-B subtypes invalidate concerns that these individuals are at a disadvantage because drugs have been designed primarily for subtype B infections.

Superinfection with drug-resistant HIV is rare and does not contribute substantially to therapy failure in a large European cohort.

BACKGROUND: Superinfection with drug resistant HIV strains could potentially contribute to compromised therapy in patients initially infected with drug-sensitive virus and receiving antiretroviral therapy. To investigate the importance of this potential route to drug resistance, we developed a bioinformatics pipeline to detect superinfection from routinely collected genotyping data, and assessed whether superinfection contributed to increased drug resistance in a large European cohort of viremic, drug treated patients. METHODS: We used sequence data from routine genotypic tests spanning the protease and partial reverse transcriptase regions in the Virolab and EuResist databases that collated data from five European countries. Superinfection was indicated when sequences of a patient failed to cluster together in phylogenetic trees constructed with selected sets of control sequences. A subset of the indicated cases was validated by re-sequencing pol and env regions from the original samples. RESULTS: 4425 patients had at least two sequences in the database, with a total of 13816 distinct sequence entries (of which 86% belonged to subtype B). We identified 107 patients with phylogenetic evidence for superinfection. In 14 of these cases, we analyzed newly amplified sequences from the original samples for validation purposes: only 2 cases were verified as superinfections in the repeated analyses, the other 12 cases turned out to involve sample or sequence misidentification. Resistance to drugs used at the time of strain replacement did not change in these two patients. A third case could not be validated by re-sequencing, but was supported as superinfection by an intermediate sequence with high degenerate base pair count within the time frame of strain switching. Drug resistance increased in this single patient. CONCLUSIONS: Routine genotyping data are informative for the detection of HIV superinfection; however, most cases of non-monophyletic clustering in patient phylogenies arise from sample or sequence mix-up rather than from superinfection, which emphasizes the importance of validation. Non-transient superinfection was rare in our mainly treatment experienced cohort, and we found a single case of possible transmitted drug resistance by this route. We therefore conclude that in our large cohort, superinfection with drug resistant HIV did not compromise the efficiency of antiretroviral treatment.

Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel.

CONTEXT: New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected adults in resource-rich settings. OBJECTIVE: To provide current recommendations for the treatment of adult HIV infection with ART and use of laboratory-monitoring tools. Guidelines include when to start therapy and with what drugs, monitoring for response and toxic effects, special considerations in therapy, and managing antiretroviral failure. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Data that had been published or presented in abstract form at scientific conferences in the past 2 years were systematically searched and reviewed by an International Antiviral Society-USA panel. The panel reviewed available evidence and formed recommendations by full panel consensus. DATA SYNTHESIS: Treatment is recommended for all adults with HIV infection; the strength of the recommendation and the quality of the evidence increase with decreasing CD4 cell count and the presence of certain concurrent conditions. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir). Alternatives in each class are recommended for patients with or at risk of certain concurrent conditions. CD4 cell count and HIV-1 RNA level should be monitored, as should engagement in care, ART adherence, HIV drug resistance, and quality-of-care indicators. Reasons for regimen switching include virologic, immunologic, or clinical failure and drug toxicity or intolerance. Confirmed treatment failure should be addressed promptly and multiple factors considered. CONCLUSION: New recommendations for HIV patient care include offering ART to all patients regardless of CD4 cell count, changes in therapeutic options, and modifications in the timing and choice of ART in the setting of opportunistic illnesses such as cryptococcal disease and tuberculosis.

Nitrosative stress and corneal transplant endothelial cell death during acute graft rejection.

BACKGROUND: Nitrosative stress takes place in endothelial cells (EC) during corneal acute graft rejection. The purpose of this study was to evaluate the potential role of peroxynitrite on corneal EC death. METHODS: The effect of peroxynitrite was evaluated in vivo. Fifty, 250, and 500 microM in 1.5 microL of the natural or denatured peroxynitrite in 50 microM NaOH, 50 microM NaOH alone, or balanced salt solution were injected into the anterior chamber of rat eyes (n=3/group). Corneal toxic signs after injection were assessed by slit-lamp, in vivo confocal imaging, pachymetry, and EC count. The effect of peroxynitrite was also evaluated on nitrotyrosine and leucocyte elastase inhibitor/LDNase II immunohistochemistry. Human corneas were incubated with peroxynitrite and the effect on EC viability was evaluated. A specific inducible nitric oxide synthase inhibitor (iNOS) was administered systemically in rats undergoing allogeneic corneal graft rejection and the effect on EC was evaluated by EC count. RESULTS: Rat eyes receiving as little as 50 microM peroxynitrite showed a specific dose-dependent toxicity on EC. We observed an intense nitrotyrosine staining of human and rat EC exposed to peroxynitrite associated with leucocyte elastase inhibitor nuclear translocation, a noncaspase dependent apoptosis reaction. Specific inhibition of iNOS generation prevented EC death and enhanced EC survival of the grafted corneas. However, inhibition of iNOS did not have a significant influence on the incidence of graft rejection. CONCLUSION: Nitrosative stress during acute corneal graft rejection in rat eyes induces a noncaspase dependent apoptotic death in EC. Inhibition of nitric oxide production during the corneal graft rejection has protective effects on the corneal EC survival.

Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study.

BACKGROUND:HIV-1-infected patients vary considerably by their response to antiretroviral treatment, drug concentrations in plasma, toxic events, and rate of immune recovery. This variability could have a genetic basis. We did a pharmacogenetics study to analyse the association between response to antiretroviral treatment and allelic variants of several genes. METHODS:In 123 patients, we did PCR analyses of the gene for the multidrug-resistance transporter (MDR1), which codes for P-glycoprotein, of genes coding for isoenzymes of cytochrome P450, CYP3A4, CYP3A5, CYP2D6, and CYP2C19, and of the gene for the chemokine receptor CCR5. We measured concentrations in plasma of the antiretroviral agents efavirenz and nelfinavir by high-performance liquid-chromatography, and measured levels of P-glycoprotein expression, CD4-cell count, and HIV-1 viraemia. FINDINGS: Median drug concentrations in patients with the MDR1 3435 TT, CT, and CC genotypes were at the 30th, 50th, and 75th percentiles, respectively (p=0.0001). In patients with CYP2D6 extensive-metaboliser or poor-metaboliser alleles, median drug concentrations were at percentiles 45 and 62.5, respectively (p=0.04). Patients with the MDR1 TT genotype 6 months after starting treatment had a greater rise in CD4-cell count (257 cells/microL) than patients with the CT (165 cells/microL) and CC (121 cells/microL) genotype (p=0.0048), and the best recovery of naïve CD4-cells. INTERPRETATION:The polymorphism MDR1 3435 C/T predicts immune recovery after initiation of antiretroviral treatment. This finding suggests that P-glycoprotein has an important role in admittance of antiretroviral drugs to restricted compartments in vivo.

Development of a vaccine strategy against human and bovine schistosomiasis: background and update

Schistosomiasis is a chronic and debilitating parasitic disease that affects over 200 million people throughout the world and causes about 500,000 deaths annually. Two specific characteristics of schistosome infection are of primordial importance to the development of a vaccine: schistosomes do not multiply within the tissues of their definitive hosts (unlike protozoan parasites) and a partial non-sterilizing immunity can have a marked effect on the incidence of pathology and on disease transmission. Since viable eggs are the cause of disease pathology, a reduction in worm fecundity whether or not accompanied by a reduction in parasite burden is a sufficient goal for vaccine induced immunity. We originally showed that IgE antibodies played in experimental models a pivotal role for the development of protective immunity. These laboratory findings have been now confirmed in human populations. Following the molecular cloning and expression of a protein 28 kDa protein of Schistosoma mansoni and its identification as a glutathion S-transferase, immunization experiments have been undertaken in several animal species (rats, mice, baboons). Together with a significant reduction in parasite burden, vaccination with Sm28 GST was recently shown to reduce significantly parasite fecundity and egg viability leading to a decrease in liver pathology. Whereas IgE antibodies were shown to be correlated with protection against infection, IgA antibodies have been identified as one of the factors affecting egg laying and viability. In human populations, a close association was found between IgA antibody production to Sm28 GST and the decrease of egg output. The use of appropriate monoclonal antibody probes has allowed the demonstration that the inhibition of parasite fecundity following immunization was related to the inhibition of enzymatic activity of the molecule. Epitope mapping of Sm28 GST has indicated the prominent role of the N and C terminal domains. Immunization with the corresponding synthetic peptides was followed by a decrease of 70% of parasite fecundity and egg viability. As a preliminary step towards phase I human trials, vaccination experiments have been performed in cattle, a natural model for Schistosoma bovis. Vaccination of calves with the S. bovis GST has led to a reduction of ever 80% of egg output and tissue egg count. Significant levels of protection were also observed in goats after immunization with the recombinant S. bovis GST. Increasing evidence of the participation of IgA antibodies in protective immunity has prompted us toward the development of mucosal immunization. Preliminary results indicate that significant levels of protection can be achieved following oral immunization with live attenuated vectors or liposomes. These studies seem to represent a promising approach towards the future development of a vaccine strategy against one of major human parasitic diseases.

La poética del desig: amor i bogeria a l'Orlando furioso

Aquesta tesina, amb el títol "La poètica del desig. amor i bogeria a l'Orlando furioso", proposa una nova lectura del poema de Ludovico Ariosto, prenent com a objectiu l'anàlisi de la bogeria del seu protagonista, el Comte Orlando, "che per amor venne in furore e matto / d'uom che sì saggio era stimato prima". Així doncs, pretenem esbrinar per què davant de la constatació de Matteo Maria Boiardo d'un "Orlando innmorato", Ariosto va respondre amb un "Orlando furioso", narrant així "cosa non detta in prosa mai né in rima". Per arribar fins al fons de la qüestió, ens hem preguntat quins són l'origen, la manifestació textual, la dimensió i el significat del concepte de "furor" en el text; interrogants que ens han conduït cap a una bogeria amorosa que és manifestació externa d'un desig insatisfet. Un concepte que, a més a més d'evocar l"Hercules furens" d'Eurípides i Sèneca, ens remet a la teoria dels humors de Galè, al concepte de 'melancholia' d'Aristòtil i a l'eròtica platònica, al mateix temps que reprodueix els models del que Cesare Segre anomena la 'follie littéraire' característica de l'època medieval. A partir d'aquesta anàlisi s'ha interpretat el text com una apologia de les passions en la que es destrona al savi com a paradigma i model ètic, acabant així amb la imatge de l'home com a "animal rationale", situant per contra la seva "humanitas" ja no en la racionalitat (tampoc en la irracionalitat), sinó en la passionalitat, oferint així un retrat de l'ésser humà com a "animal passionalis" , una criatura intermitja en la que haurien de confluir idealment raó i passió.

Head motion detection using FID navigators.

This work explores a concept for motion detection in brain MR examinations using high channel-count RF coil arrays. It applies ultrashort (<100 μsec) free induction decay signals, making use of the knowledge that motion induces variations in these signals when compared to a reference free induction decay signal. As a proof-of-concept, the method was implemented in a standard structural MRI sequence. The stability of the free induction decay-signal was verified in phantom experiments. Human experiments demonstrated that the observed variations in the navigator data provide a sensitive measure for detection of relevant and common subject motion patterns. The proposed methodology provides a means to monitor subject motion throughout a MRI scan while causing little or no impact on the sequence timing and image contrast. It could hence complement available motion detection and correction methods, thus further reducing motion sensitivity in MR applications.

Normal glucagon signaling and β-cell function after near-total α-cell ablation in adult mice.

OBJECTIVEEvaluate whether healthy or diabetic adult mice can tolerate an extreme loss of pancreatic α-cells and how this sudden massive depletion affects β-cell function and blood glucose homeostasis.RESEARCH DESIGN AND METHODSWe generated a new transgenic model allowing near-total α-cell removal specifically in adult mice. Massive α-cell ablation was triggered in normally grown and healthy adult animals upon diphtheria toxin (DT) administration. The metabolic status of these mice was assessed in 1) physiologic conditions, 2) a situation requiring glucagon action, and 3) after β-cell loss.RESULTSAdult transgenic mice enduring extreme (98%) α-cell removal remained healthy and did not display major defects in insulin counter-regulatory response. We observed that 2% of the normal α-cell mass produced enough glucagon to ensure near-normal glucagonemia. β-Cell function and blood glucose homeostasis remained unaltered after α-cell loss, indicating that direct local intraislet signaling between α- and β-cells is dispensable. Escaping α-cells increased their glucagon content during subsequent months, but there was no significant α-cell regeneration. Near-total α-cell ablation did not prevent hyperglycemia in mice having also undergone massive β-cell loss, indicating that a minimal amount of α-cells can still guarantee normal glucagon signaling in diabetic conditions.CONCLUSIONSAn extremely low amount of α-cells is sufficient to prevent a major counter-regulatory deregulation, both under physiologic and diabetic conditions. We previously reported that α-cells reprogram to insulin production after extreme β-cell loss and now conjecture that the low α-cell requirement could be exploited in future diabetic therapies aimed at regenerating β-cells by reprogramming adult α-cells.

Ultrastructural aspects of spermatogonesis in Metamicrocotyla macracantha (Alexander, 1954) Koratha, 1955 (Monogenea; Microcotylidae)

Ultrastructural aspects of spermatogenesis, spermiogenesis and of the mature spermatozoon of a microcotylid monogenean Metamicrocotyla macracantha parasite from Mugil liza, are described. The irregularly-shaped spermatogonia divides by successive mitoses, forming the primary spermatocytes, identified by the presence of synaptonemal complexes in their nuclei. The spermatids formed by meiotic cell divisions of the secondary spermatocytes, differentiate into a mature spermatozoon. Cross sections of the head and the middle region of mature spermatozoa show the nucleus with strong condensed chromatin, the mitochondria with short cristae, peripheral microtubules and two axonemes with a 9+1 pattern, confirming the characteristics of this genus.

Extended truncated Tweedie-Poisson model

It has been argued that by truncating the sample space of the negative binomial and of the inverse Gaussian-Poisson mixture models at zero, one is allowed to extend the parameter space of the model. Here that is proved to be the case for the more general three parameter Tweedie-Poisson mixture model. It is also proved that the distributions in the extended part of the parameter space are not the zero truncation of mixed poisson distributions and that, other than for the negative binomial, they are not mixtures of zero truncated Poisson distributions either. By extending the parameter space one can improve the fit when the frequency of one is larger and the right tail is heavier than is allowed by the unextended model. Considering the extended model also allows one to use the basic maximum likelihood based inference tools when parameter estimates fall in the extended part of the parameter space, and hence when the m.l.e. does not exist under the unextended model. This extended truncated Tweedie-Poisson model is proved to be useful in the analysis of words and species frequency count data.

Laboratory indicators for monitoring HIV disease

Immunological monitoring of disease progression following HIV infection and seroconversion illness, latency and AIDS, not only helps in the basic investigation of the natural history of the viral infection in man, but also can assist in prognosis and treatment of AIDS-defining illnesses. However, outside clinical trials, these tests should be selected and used in clinical practice only if they are validated as relevant and effective. The absolute CD4+ T-helper lymphocyte count, measured by flow cytometry, has emerged as the best available investigation, but needs care in sampling due to diurnal and circadian rhythms, effects of age, pregnancy, therapy, intercurrent infections and technique. Sampling should provide a baseline and trends - monthly intervals initially, then quarterly in uncomplicated cases. Thresholds may be given for counts (e.g. 200/µl) below which prophylaxis against pneumocystis pneumonia should be administered, and repeating persistently low counts (e.g. below 50/µl) is seldom helpful in practice. Serum levels of beta-2 microglobulin, neopterin and immunoglobulins rarely add information. Physicians and laboratories should have testing guidelines based on clinical audit of best practice, based in turn on scientific understanding of the immunological processes involved.