Dissecting the respective roles of microbiota and host genetics in the susceptibility of Card9-/- mice to colitis.

BACKGROUND: The etiology of inflammatory bowel disease (IBD) is unclear but involves both genetics and environmental factors, including the gut microbiota. Indeed, exacerbated activation of the gastrointestinal immune system toward the gut microbiota occurs in genetically susceptible hosts and under the influence of the environment. For instance, a majority of IBD susceptibility loci lie within genes involved in immune responses, such as caspase recruitment domain member 9 (Card9). However, the relative impacts of genotype versus microbiota on colitis susceptibility in the context of CARD9 deficiency remain unknown. RESULTS: Card9 gene directly contributes to recovery from dextran sodium sulfate (DSS)-induced colitis by inducing the colonic expression of the cytokine IL-22 and the antimicrobial peptides Reg3ß and Reg3γ independently of the microbiota. On the other hand, Card9 is required for regulating the microbiota capacity to produce AhR ligands, which leads to the production of IL-22 in the colon, promoting recovery after colitis. In addition, cross-fostering experiments showed that 5 weeks after weaning, the microbiota transmitted from the nursing mother before weaning had a stronger impact on the tryptophan metabolism of the pups than the pups' own genotype. CONCLUSIONS: These results show the role of CARD9 and its effector IL-22 in mediating recovery from DSS-induced colitis in both microbiota-independent and microbiota-dependent manners. Card9 genotype modulates the microbiota metabolic capacity to produce AhR ligands, but this effect can be overridden by the implantation of a WT or "healthy" microbiota before weaning. It highlights the importance of the weaning reaction occurring between the immune system and microbiota for host metabolism and immune functions throughout life. A better understanding of the impact of genetics on microbiota metabolism is key to developing efficient therapeutic strategies for patients suffering from complex inflammatory disorders. Video Abstract.

High copper concentration reduces biofilm formation in Acidithiobacillus ferrooxidans by decreasing production of extracellular polymeric substances and its adherence to elemental sulfur.

Acidithiobacillus ferrooxidans is an acidophilic bacterium able to grow in environments with high concentrations of metals. It is a chemolithoautotroph able to form biofilms on the surface of solid minerals to obtain its energy. The response of both planktonic and sessile cells of A. ferrooxidans ATCC 23270 grown in elemental sulfur and adapted to high copper concentration was analyzed by quantitative proteomics. It was found that 137 proteins varied their abundance when comparing both lifestyles. Copper effllux proteins, some subunits of the ATP synthase complex, porins, and proteins involved in cell wall modification increased their abundance in copper-adapted sessile lifestyle cells. On the other hand, planktonic copper-adapted cells showed increased levels of proteins such as: cupreredoxins involved in copper cell sequestration, some proteins related to sulfur metabolism, those involved in biosynthesis and transport of lipopolysaccharides, and in assembly of type IV pili. During copper adaptation a decreased formation of biofilms was measured as determined by epifluorescence microscopy. This was apparently due not only to a diminished number of sessile cells but also to their exopolysaccharides production. This is the first study showing that copper, a prevalent metal in biomining environments causes dispersion of A. ferrooxidans biofilms. SIGNIFICANCE: Copper is a metal frequently found in high concentrations at mining environments inhabitated by acidophilic microorganisms. Copper resistance determinants of A. ferrooxidans have been previously studied in planktonic cells. Although biofilms are recurrent in these types of environments, the effect of copper on their formation has not been studied so far. The results obtained indicate that high concentrations of copper reduce the capacity of A. ferrooxidans ATCC 23270 to form biofilms on sulfur. These findings may be relevant to consider for a bacterium widely used in copper bioleaching processes.

Péptidos tóxicos y no tóxicos de cianobacterias en cuerpos de agua dulce de la V Región, Chile / Toxic and non toxic cyanobacterial peptides in freshwater bodies from the V Region, Chile

En Chile se ha detectado la presencia de algunos géneros de cianobacterias que pueden producir potentes hepatotoxinas y neurotoxinas, las que pueden ser letales para humanos y animales. En el presente trabajo se determinó la presencia de dos géneros de cianobacterias no tóxicos: Chroococcus y Spirulina; y cuatro géneros de cianobacterias productores de toxina, Anabaena, Anabaenopsis, Microcystis y Oscillatoria en tres diferentes cuerpos de agua de la V Región: Lago Peñuelas (Valparaíso), Tranque Recreo (Villa Alemana) y Embalse Los Aromos (Limache). Además se detectó la presencia de hepatotoxinas por MALDI-TOF MS encontrándose microcistina-RR, -LA, -YR y nodularina en Embalse Los Aromos, microcistina-LA en Tranque Recreo y microcistina-RR y LA en Lago Peñuelas. Adicionalmente en algunas de las muestras se detectó la presencia de péptidos no tóxicos, que presentan actividad biológica tales como aeruginosinas, cianopeptolinas y microgininas. Como estos cuerpos de agua dulce son utilizados para abastecimiento público y para la recreación, es importante diseñar planes de tratamiento y monitoreo para detectar y evitar los riesgos a la salud humana y animal provocado por estos microorganismos.

In Chile the presence of some genera of cyanobacteria that may cause potent hepatoxins and neurotoxis has been detected, which may become lethal for man and animal. In this paper the occurrence of two non toxic genera of cyanobacteria: Chroococcus and Spirulina was established along with four genera of toxin-producing cyanobacteria, Anabaena, Anabaenopsis, Microcystis and Oscillatoria in three different masses of water from the V Region: Lago Peñuelas (Valparaíso), Tranque Recreo (Villa Alemana) and Embalse Los Aromos (Limache). Likewise the presence of hepatoxins by MALDI-TOF MS was detected which resulted in the occurrence of microcystina-RR, _LA , -YR and nodularina in Embalse Los Aromos, microcystina –LA in Tranque Recreo and microcystina -RR and LA in Lago Peñuelas. Moreover, the presence of non toxic peptides developing biological activities such as aeruginosinas, cianopeptolins and microgininines was detected. Considering that these freshwater bodies are intended for public supply and recreational purposes, it is of utmost importance to design treatment and supervising plans in order to detect and prevent risks for human and animal health caused by these microorganisms.

A placebo-controlled trial of gabapentin for painful HIV-associated sensory neuropathies.

BACKGROUND: Painful HIV-associated sensory neuropathies (HIV-SN) are a common complication of HIV infection. The pathogenesis is unknown and the treatment very limited. Gabapentin (GBP) is effective in painful diabetic neuropathy and postherpetic neuralgia and its effectiveness on painful HIV-SN has been reported anecdotally. DESIGN: Multicenter, prospective, randomised, double-blind, placebo-controlled study. METHODS: Patients were followed for a 1-week screening, a 4-week double-blind and a 2-week open treatment phase. GBP was initiated at 400 mg/d, titrated over 2 weeks to 1200 mg/d, and then either maintained at this level or-if not beneficial-titrated to 2400 mg/d. After 4 weeks the medication was unblinded and the patient had the choice to begin, to maintain or to increase GBP to 3600 mg/d. The primary outcome measure was an improvement in median pain on the Visual Analogue Scale (VAS) from the screening week compared to the 4(th) treatment week. A secondary efficacy measure was the median sleep score (VAS). RESULTS: 15 patients received GBP and 11 placebo. In each group one patient dropped out during the doubleblind phase. Median pain (GBP 5.1; placebo 4.7) and sleep score (GBP 4.5; placebo 5.6) did not differ between both groups at baseline. In the GBP-group there was a significant decrease of the pain to 2.85 (-44.1 %) as well as of the sleep VAS to 2.3 (-48.9 %). No significant decrease in the pain (median VAS=3.3, -29.8 %) as well as in the sleep score (median VAS=4.95, -11.6 %) was observed in the placebo-group. GBP was generally well tolerated. The most frequent side effect was somnolence reported in 80% of GBP-treated patients. CONCLUSIONS: GBP was more effective than placebo in reducing pain and sleep interference in patients with HIV-SN.

[Supplementary history and occupational dermatologic evaluation of medical bath workers, masseurs, and physical therapists]. / Anamneseauxilium und gewerbedermatologische Beurteilung bei medizinischen Bademeistern, Masseuren und Physiotherapeuten.

The various noxious agents to which these occupational groups can be exposed are described in detail. We have constructed a supplementary questionnaire to aid the occupational dermatologist in evaluating such individuals. We describe measures for skin protection, and methods for reduce exposure of harmful agents.

Managing healthcare: a view of tomorrow.

This paper presents a vision of the future in which standards exist at all levels necessary to accomplish true interoperability. The infrastructure has been established to support connectivity among all healthcare-related institutions as well as the population at large. Provider and patient care integrated in the process of an individual's care.

Integration of a computer-based patient record system into the primary care setting.

The use of computer-based patient record systems (CPRS) in the primary care setting will increase significantly over the next few years. Real-time, point-of-care use of such systems must provide adequate payback to justify the intrusion into the provider/patient relationship. The authors describe, through the transition of a legacy system into a state-of-the art system, how such a system might be integrated into the primary care setting. Information flow is organized around an event, such as a patient encounter, or around the patient. The Medical Record (TMR) optimizes the provider/computer interaction through the use of protocols and clinical guidelines. Documentation is enhanced through the use of computer-generated progress notes.

Role of pericardial constraint for right ventricular function in humans.

STUDY OBJECTIVE: To analyze the extent of pericardial constraint on right ventricular function in humans. PATIENTS AND METHODS: Twenty patients, 59 +/- 2 (mean +/- SEM) years old, undergoing coronary bypass surgery. Right ventricular volumes and pressures were evaluated using a rapid response Swan-Ganz thermodilution catheter. INTERVENTIONS: Parameters were determined before and after pericardiotomy, both before and during increased right ventricular systolic pressure by partial compression of the pulmonary artery (before pulmonary compression: 25 +/- 1 mm Hg; during: 39 +/- 1 mm Hg). RESULTS: Pericardiotomy alone did not significantly affect right ventricular end-diastolic volume (before: 79 +/- 4 mL m-2; after: 78 +/- 3 mL m-2), right ventricular ejection fraction (before: 48 +/- 1%; after: 48 +/- 2%), and right atrial pressure (before: 4.3 +/- 0.8 mm Hg; after: 4.3 +/- 0.7 mm Hg). Before pericardiotomy, the increase in right ventricular afterload significantly increased right atrial pressure (to 5.5 +/- 0.7 mm Hg, p < 0.05) and reduced right ventricular ejection fraction (to 43 +/- 2%, p < 0.01). Right ventricular end-diastolic volume remained unchanged. After pericardiotomy, the increase in right ventricular afterload significantly increased right ventricular end-diastolic volume (to 85 +/- 3 mL m-2, p < 0.01) and also reduced right ventricular ejection fraction (to 42 +/- 2%, p < 0.01), while right atrial pressure was not significantly changed. During increased right ventricular afterload, the right ventricular diastolic pressure-volume relation was shifted rightward. CONCLUSIONS: At normal levels of right ventricular diastolic filling, the pericardium does not exert constraining effects on right ventricular function. However, with increasing levels of right ventricular preload, pericardial constraint significantly influences right ventricular function in humans.

A chartless record--is it adequate?

The computerized medical record supported by The Medical Record (TMR) has been the only record of physician-patient encounters on the nephrology service of the Durham Veterans Administration Medical Center since April 1981. Physicians using the system evaluated the adequacy of the computerized record as a replacement for the paper chart. The computerized record was able to capture and display all pertinent data. Manual or computerized narratives provided a useful supplement to the core computerized record only in those rare instances that a physician needed to point out which of the data in the record were important to his decision making.