867 resultados para Symptoms of diseases


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OBJECTIVES: To investigate the influence of prenatal hospitalization before a premature birth, on the parental stressful experience, parental symptoms of post-traumatic stress and quality of parent-infant interaction during the hospitalization in neonatology. POPULATION AND METHODS: Population: 51 preterm infants born and 25 full term infants control. Four groups: controls, premature without prenatal hospitalization, premature with a short (<8 days) prenatal hospitalization and premature with a long (≥8 days) prenatal hospitalization. Instruments: the Parental Stressor Scale: Neonatal Intensive Care Unit (PSS: NICU, Miles et al., 1993 [14]) and the Perinatal PTSD Questionnaire (PPQ, Quinnell and Hynan, 1999 [16]). RESULTS: When prenatal hospitalization of the mother occurred, parents acknowledged increased stress induced by the environmental factors during the infant's hospitalization. Furthermore, mothers from the group with a short prenatal hospitalization presented significantly more symptoms of post-traumatic stress. Parents presenting more symptoms of post-traumatic stress describe a significantly more difficult interaction with their infant in neonatology. CONCLUSION: This study highlights the necessity to deliver special care to women hospitalized shortly (<8 days) prior to the delivery of their premature baby. This group is at high risk of presenting post-traumatic stress symptoms, which could have a negative impact on the quality of parent-infant interactions.

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This integrative literature review aimed to characterize scientific articles on health-related quality of life – HRQoL – among patients with advanced cancer from national and international literature, and summarize those factors evidenced in the literature that contributed to the improvement or worsening of HRQoL among patients with advanced cancer. The search for materials was conducted in the following databases: CINAHL, EMBASE, PubMed, SciELO and LILACS. Among the 21 articles in the sample, 13 showed an improvement of HRQoL among patients with advanced cancer related to the development of physical, emotional and spiritual interventions. In eight studies, we identified predictive symptoms of low HRQoL, such as pain, fatigue, sleep disorders, depression, nutritional changes, and others. The results showed that clinical manifestations, which many times were inherent in cancer, such as factors that can lower patients’ HRQoL, while physical, psychological and spiritual benefits resulting from therapeutic interventions may promote its improvement.


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Objective To assess the effectiveness of Problem-Solving Therapy (PST) on family caregivers through the use of scales to measure anxiety, depression and emotional distress; and to explore facilitating factors and obstacles for its use based on the narrative of nurses. Method A clinical trial and an exploratory focus group with the use of mixed analysis methodology. The study was conducted in a primary health care center in Tarragona, Spain, and the sample consisted of 122 family caregivers who were included in the home care service, and 10 nurses who participated in the intervention group. Family caregivers with evident symptoms of anxiety, depression and emotional distress received PST in the intervention group. The intervention group also consisted of a discussion with eight nurses, which was transcribed and submitted to content analysis. Conclusion Problem-Solving Therapy proved to be effective in reducing perceived anxiety, depression and emotional distress. We identified its strong points and obstacles as described by nurses.



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Introduction: Few studies have reported the distribution of all hospital admissions at the entire country level in low and middle-income countries (LMICs). We examined this question in Seychelles, a rapidly developing small island state in the Africa region, in which access to health care is provided free of charge to all inhabitants through a national health system and all hospital admissions are routinely registered. Methods: Based on all admissions to all hospitals in Seychelles in 2005-2008, we calculated the distribution of hospital admissions, age at admission, length of stay and bed occupancy (i.e. cumulated number of patients * number of days spent in all hospitals) according to both hospital departments and broad causes of diseases (using codes of the ICD-10 classification of diseases). Results: Bed occupancy was largest in the surgical wards (36.7% of all days spent in all hospitals), followed by the medical wards (24.3%), gynecology/obstetrics wards (18.4%), pediatric wards (11.2%), and psychiatric wards (7.2%). According to broad causes of diseases/conditions, bed occupancy was highest for obstetrics/gynecology conditions (19.9% of all days spent at hospital), mental diseases (8.6%), cardiovascular diseases (8.1%), upper aerodigestive/pulmonary diseases (8%), infectious/parasitic diseases (8%), gastrointestinal diseases (7.2%), and urogenital diseases (6.7%). Adjusted to 100'000 population, 153 hospital beds are needed every day, including 31 for obstetrics/gynecologic conditions, 13 for mental diseases, 12 for cardiovascular diseases, 12 for upper aerodigestive diseases, 12 for infectious/parasitic diseases, and 11 for gastrointestinal diseases. Conclusion: Our findings give a good indication of the overall distribution of admissions according to both hospital departments and broad causes of diseases in a middle-income country. These findings provide important information for health care planning at the national level

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OBJECTIVE To analyze the self-care behaviors according to gender, the symptoms of depression and sense of coherence and compare the measurements of depression and sense of coherence according to gender. METHOD A correlational, cross-sectional study that investigated 132 patients with decompensated heart failure (HF). Data were collected through interviews and consultation to medical records, and analyzed using the chi-square and the Student's t tests with significance level of 0.05. Participants were 75 men and 57 women, aged 63.2 years on average (SD = 13.8). RESULTS No differences in self-care behavior by gender were found, except for rest after physical activity (p = 0.017). Patients who practiced physical activity showed fewer symptoms of depression (p<0.001). There were no differences in sense of coherence according to self-care behavior and gender. Women had more symptoms of depression than men (p = 0.002). CONCLUSION Special attention should be given to women with HF considering self-care and depressive symptoms.

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Malaria has occurred in the Cabo Verde archipelago with epidemic characteristics since its colonization. Nowadays, it occurs in Santiago Island alone and though prophylaxis is not recommended by the World Health Organization, studies have highlight the prospect of malaria becoming a serious public health problem as a result of the presence of antimalarial drug resistance associated with mutations in the parasite populations and underscore the need for tighter surveillance. Despite the presumptive weak immune status of the population, severe symptoms of malaria are not observed and many people present a subclinical course of the disease. No data on the prevalence of sicklecell trait and red cell glucose-6-phosphate dehydrogenase deficiency (two classical genetic factors associated with resistance to severe malaria) were available for the Cabo Verde archipelago and, therefore, we studied the low morbidity from malaria in relation to the particular genetic characteristics of the human host population. We also included the analysis of the pyruvate kinase deficiency associated gene, reported as putatively associated with resistance to the disease. Allelic frequencies of the polymorphisms examined are closer to European than to African populations and no malaria selection signatures were found. No association was found between the analyzed human factors and infection but one result is of high interest: a linkage disequilibrium test revealed an association of distant loci in the PKLR gene and adjacent regions, only in non-infected individuals. This could mean a more conserved gene region selected in association to protection against the infection and/or the disease.

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The leishmaniases are a group of diseases transmitted by the bite of Leishmania infected female phlebotomine sand flies. The diseases occur in different forms: localized, diffuse and muco-cutaneous leishmaniasis, and visceral leishmaniasis (VL). Inside macrophages, the main host cells of the obligate intracellular Leishmania parasites, nitric oxide synthase and arginase can regulate parasite killing or growth. In experimental leishmaniasis, we previously reported that non-healing disease is associated with higher arginase activity at site of pathology, correlating with local suppression of T cell function. To test whether these data translate to human leishmaniasis, the following study was initiated: I first tested the hypothesis that local suppression of T cell responses observed in persistent CL is associated with arginase induced L-arginine depletion. The results showed that arginase activity is increased at site of pathology compared to peripheral blood mononuclear cells (PBMCs) of LCL patients and intact skin of healthy controls. The phenotype of arginase expressing cells was identified in both compartments as CD15+ CD14|0W low-density granulocytes (LDGs). Finally, high arginase activity at site of pathology observed in cutaneous lesions of patients coincides with downregulation of CD3Ç, CD4 and CD8 molecules in CD4+ and CD8+ T cells at site of pathology. We concluded that increased arginase levels in lesions of LCL patients might contribute to CL pathogenesis by impairing T cell effector function at site of pathology. Next, it was tested whether arginase, an enzyme associated with immunosuppression, is higher in patients with VL and contributes to impaired T cell function through depletion of L- arginine. The results showed that higher level of arginase activity in the PBMC coincides with active phase of VL. Cells expressing arginase in PBMCs were also found to be LDGs. Importantly, increased arginase activity and frequency of degranulated neutrophils coincided with lower plasma L-arginine levels. Furthermore, downregulation of CD3Ç, in T cells correlated with low plasma arginine levels. VL/HIV co-infection is a frequently reported leishmaniasis complication in Ethiopia associated with poor prognosis, with up to 40% mortality rate and high relapse rate. Arginase activity was significantly increased in PBMCs and plasma of VL patients co-infected with HIV than in those having VL alone. Similarly, cells expressing arginase in PBMCs were found to be LDGs. In summary, the results presented here show that increased arginase activity is a marker of disease severity in human leishmaniasis with and without HIV; further, these results suggest that arginase mediated L-arginine depletion may inhibit T cell function and contribute to impaired control of infection. - Les leishmanioses sont un groupe de maladies transmises par la piqûre de mouches des sables femelles, appelées phlébotomes, ayant été infectées par Leishmania. Les maladies se manifestent sous différentes formes: la leishmaniose cutanée localisée, la leishmaniose diffuse et mucocutanée et la leishmaniose viscérale (LV). A l'intérieur des macrophages, les principales cellules hôtes des parasites, l'oxyde nitrique synthase et l'arginase, peuvent contrôler, soit la mort du parasite, soit sa croissance. Pour la leishmaniose expérimentale, nous avons déjà rapporté que le développement de lesions qui ne guérissent pas est associé à une activité plus grande d'arginase au site d'infection, en corrélation avec la suppression locale de la fonction des cellules T. Pour vérifier si ces données pouvaient s'appliquer à la leishmaniose humaine, j'ai d'abord vérifié l'hypothèse selon laquelle la suppression locale des réponses des cellules T observée dans la CL persistante, est associée à la la diminution de L- arginine induite par l'arginase. Les résultats ont montré que l'activité arginase est augmentée au site d'infection, par rapport aux cellules mononucléées du sang périphérique (CMSP) de patients LCL et à la peau intacte des contrôles sains. Le phénotype de cellules exprimant l'arginase a été identifié dans les deux compartiments comme des granulocytes CD15+ et CD 14" de basse densité (LDG). Enfin, l'activité arginase élevée au site de la pathologie, observée dans les lésions cutanées de patients, coïncide avec la reduction dde l'expression des molécules CD3Ç, CD4 et CD8 dans les cellules T CD4+ et CD8+ au site de pathologie . Nous avons conclu que l'augmentation des niveaux d'arginase dans les lésions de patients LCL pourrait contribuer à la pathogenèse de la CL, en altérant la fonction effectrice des celllules T au site de la pathologie. Ensuite, nous avons vérifié si l'arginase, une enzyme associée à l'immunosuppression, était plus élevée chez les patients atteints de VL et si elle contribuait à la mauvaise fonction des cellules T par la depletion en L-arginine. Les résultats ont montré qu'un niveau plus élevé de l'activité arginase dans les PBMC correspond à la phase active de la VL. Les cellules exprimant l'arginase dans les CMSP se sont révélées à être de type LDG . Il est important de souligner que l'augmentation de l'activité arginase et la fréquence des neutrophiles dégranulés a coïncidé avec des niveaux inférieurs de L-arginine plasmatique. En outre, la suppression de CD3Ç dans les cellules T correlle avec de faibles niveaux d'arginine plasmatique . Il a été fréquement rapporté que la co-infection VL/VIH est une complication de la leishmaniose en Ethiopie, associée à un mauvais prognostic, un taux de mortalité pouvant atteindre 40% et un pourcentage élevé de rechutes. L'activité de l'arginase a beaucoup plus augmentée dans les CMSP et le plasma de patients atteints de VL et co-infectés par le VIH, que chez ceux seulement attaints de VL. De même, les cellules exprimant l'arginase dans les CMSP sont aussi des LDG. En résumé, les résultats présentés ici montrent que l'augmentation de l'activité de l'arginase est un marqueur de gravité de la la leishmaniose humaine, avec ou sans VIH ; en outre, ces résultats suggèrent que la déplétion de L-arginine par l'arginase pourrait inhiber la fonction des cellules T et contribuer à un contrôle réduit de l'infection. - Les Leishmanioses sont des maladies parasitaires transmises par la piqûre d'une mouche des sables femelle (phlébotome) infectée par Leishmania. La maladie se manifeste sous différentes formes cliniques : la leishmaniose viscérale, une maladie progressive mortelle en l'absence de traitement, la leishmaniose muco-cutanée (MCL), la leishmaniose cutanée diffuse (LCD ) maladie mutilante, qui peut être de longue durée et la leishmaniose cutanée localisée maladie dont on guérit mais laissant une cicatrice inesthétique à vie. La maladie est largement répandue, elle affecte les populations les plus pauvres dans 98 pays et 350 millions de personnes à risque. Globalement on estime à 500.000 les nouveaux cas de la forme viscérale et 1-1.5 million ceux de la leishmaniose cutanée. La leishmaniose est fortement endémique en Ethiopie et se manifeste dans les formes viscérale et cutanée. Le parasite Leishmania infecte et se multiplie dans les cellules du système immunitaire, principalement les macrophages. Les macrophages sont capables de tuer le parasite Leishmania s'ils reçoivent des instructions correctes de la part d'autres cellules du système immunitaire, les lymphocytes. Les macrophages expriment deux enzymes importants, appelés oxide nitrique synthase inductible (iNOS ) et l'arginase, qui sont respectivement associés à la promotion de la mort du parasite et la multiplication. L'enzyme iNOS présent dans les macrophages métabolise l'arginine afin de générer de l'oxyde d'azote (NO) , une molécule effectrice nécessaire pour tuer le parasite . Au contraire, lorsque les macrophages sont activés d'une certaine manière conduisant à l'augmention de la régulation de l'arginase, ils métabolisent l'arginine en polyamines qui favorisent la croissance du parasite. Au cours du développement de la leishmaniose, les lymphocytes ne parviennent pas à transmettre aux macrophages les signaux nécessaires pour tuer le parasite. Les mécanismes cellulaires qui sont la cause de ce défaut, ne sont pas bien compris. En utilisant des modèles animaux, nous avons montré la régulation à la hausse de l'arginase au site de la pathologie, qui s'est traduit par l'altération de la fonction effectrice des lymphoctes. Nous avons initié des études de leishmaniose humaine en Ethiopie afin d'identifier le rôle de l'arginase dans la sévérité de la maladie. Nos résultats montrent, que l'arginase est fortement augmentée dans la lésion des patients CL, et dans le sang des patients VL et ceux co-infectés par VL / VIH. Le niveau d' arginase régulée à la hausse coincide avec l'expression inférieure d'une molécule de signalisation dans les lymphocytes, qui est essentielle à leur bon fonctionnement. En VL actif, l'augmentation d'arginase se traduit par la diminution de l'arginine qui est indispensable à la synthèse de NO et au bon fonctionnement des lymphocytes. Ainsi, l'incapacité des lymphocytes à envoyer des signaux adéquats aux macrophages pourrait être due à la suppression de l'arginine.

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A bananeira tem um elevado valor social e económico para Cabo Verde, desempenhando um papel fundamental na dieta alimentar das populações. Nos últimos anos a produtividade da cultura tem vindo a decair e de entre as causas responsáveis pelo declínio dos bananais incluem-se micoses. Com a finalidade de determinar o possível envolvimento de fungos nas doenças foliares fez-se o levantamento da micobiota associada a necroses foliares. Material foliar com lesões de diversos tipos foi recolhido em bananais de 10 localidades da Ilha de Santiago e observado ou colocado em câmara húmida sobre meio gelosado. As estruturas de fungos detectadas sobre as folhas foram montadas em lactofenol e utilizadas para identificação até ao nível da espécie, dos fungos registados, utilizando para o efeito critérios clássicos em sistemática micológica. Foram identificados 48 táxones, sendo 44 fungos mitospóricos e 4 fungos ascomicetas. Muitos dos fungos identificados não são considerados fitopatogénicos na bananeira, estando referidos como endófitos ou saprófitas na cultura. Os principais fungos patogénicos identificados foram Cladosporium musae, Colletotrichum gloeosporiodes, C. musae, Cordana musae, Deightoniella torulosa, Lasiodiplodia theobromae e Ramichloridium musae. A maioria das espécies apresentou larga distribuição nas zonas de produção amostradas.

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BACKGROUND: Sodium wasting during the night has been postulated as a potential pathophysiological mechanism in patients suffering from orthostatic hypotension due to severe autonomic deficiency. METHODS: In this study, the diurnal variations in creatinine clearance, sodium excretion and segmental renal tubular handling of sodium were evaluated in 18 healthy subjects and 20 young patients with orthostatic hypotension (OH). In addition, 24-hour ambulatory blood pressure and the neuro-hormonal response to changes in posture were determined. The patients and their controls were studied on a free sodium intake. In a second protocol, 10 controls and 10 patients were similarly investigated after one week of a high salt diet (regular diet + 6 g NaCl/day). RESULTS: Our results demonstrate that, in contrast to normal subjects in whom no significant changes in glomerular filtration, sodium excretion and segmental sodium reabsorption were observed throughout the day, patients with OH were characterized by a significant increase in glomerular filtration rate during the nighttime (P = 0.03) and significant increases in urinary lithium excretion (P < 0.05) and lithium clearance (P = 0.05) during the night, suggesting a decreased proximal reabsorption of sodium. On a high sodium diet, the symptoms of orthostatic hypotension and the circadian variations in sodium reabsorption were significantly blunted. CONCLUSIONS: These results suggest that, while the patient is in a supine position the effective blood volume of those with OH becomes excessive due to the increased venous return. Hence, the kidney responds with an increase in glomerular filtration and a relative escape of sodium from the proximal tubular segments. These circadian variations in renal sodium handling may contribute to the maintenance of the orthostatic syndrome.

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Overactive bladder (OAB) is a prevalent condition with 16% of adults having one or more symptoms that significantly affect quality of life. Transcutaneous electrical nerve stimulation and neuromodulators have had success in treating OAB but are expensive, invasive, and sometimes cumbersome. We developed an alternative neuromodulatory technique that involves electromagnetic stimulation of the sacral nerve roots with a portable electromagnetic device to produce trans-sacral stimulation of the S3 and S4 sacral nerve roots. The aim of this study was to evaluate the impact of this device on OAB symptoms in women with a prospectively randomised double-blind controlled study. Following a power analysis, women with symptoms of OAB were prospectively recruited with ethical approval for randomisation to an active treatment (n = 33) or placebo group (n = 30) in a double-blind trial. The patient, at home, used the belt device daily for 20 min over 12 weeks. Outcome measures included a 3-day voiding diary, 1 h pad test, visual analogue score (VAS) for symptom impact (0-100%), Kings Health Questionnaire (KHQ) and Australian Quality of Life questionnaire (AQOL) at baseline, 6 and 12 weeks. Overall, no difference was found between groups for any of the research questions. Specifically, we were unable to demonstrate any difference between the active and sham device groups in frequency, nocturia, urinary leakage, or quality of life, nor was there any evidence of a placebo effect. The quality of the data was high with the number of missing observations (especially for disease specific KHQ and general AQOL) being few. This attempt to promote trans-sacral electromagnetic neuromodulation with a specially created device was ineffective on the symptoms of OAB.

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The macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that recently emerged as an attractive therapeutic target for a variety of diseases. A diverse panel of fully human anti-MIF antibodies was generated by selection from a phage display library and extensively analyzed in vitro. Epitope mapping studies identified antibodies specific for linear as well as structural epitopes. Experimental animal studies revealed that only those antibodies binding epitopes within amino acids 50-68 or 86-102 of the MIF molecule exerted protective effects in models of sepsis or contact hypersensitivity. Within the MIF protein, these two binding regions form a β-sheet structure that includes the MIF oxidoreductase motif. We therefore conclude that this β-sheet structure is a crucial region for MIF activity and a promising target for anti-MIF antibody therapy.

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Impairment of lung liquid absorption can lead to severe respiratory symptoms, such as those observed in pulmonary oedema. In the adult lung, liquid absorption is driven by cation transport through two pathways: a well-established amiloride-sensitive Na(+) channel (ENaC) and, more controversially, an amiloride-insensitive channel that may belong to the cyclic nucleotide-gated (CNG) channel family. Here, we show robust CNGA1 (but not CNGA2 or CNGA3) channel expression principally in rat alveolar type I cells; CNGA3 was expressed in ciliated airway epithelial cells. Using a rat in situ lung liquid clearance assay, CNG channel activation with 1 mM 8Br-cGMP resulted in an approximate 1.8-fold stimulation of lung liquid absorption. There was no stimulation by 8Br-cGMP when applied in the presence of either 100 μM L: -cis-diltiazem or 100 nM pseudechetoxin (PsTx), a specific inhibitor of CNGA1 channels. Channel specificity of PsTx and amiloride was confirmed by patch clamp experiments showing that CNGA1 channels in HEK 293 cells were not inhibited by 100 μM amiloride and that recombinant αβγ-ENaC were not inhibited by 100 nM PsTx. Importantly, 8Br-cGMP stimulated lung liquid absorption in situ, even in the presence of 50 μM amiloride. Furthermore, neither L: -cis-diltiazem nor PsTx affected the β(2)-adrenoceptor agonist-stimulated lung liquid absorption, but, as expected, amiloride completely ablated it. Thus, transport through alveolar CNGA1 channels, located in type I cells, underlies the amiloride-insensitive component of lung liquid reabsorption. Furthermore, our in situ data highlight the potential of CNGA1 as a novel therapeutic target for the treatment of diseases characterised by lung liquid overload.

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Postmortem imaging is increasingly used in forensic practice in cases of natural deaths related to cardiovascular diseases, which represent the most common causes of death in developed countries. While radiological examination is generally considered to be a good complement for conventional autopsy, it was thought to have limited application in cardiovascular pathology. At present, multidetector computed tomography (MDCT), CT angiography, and cardiac magnetic resonance imaging (MRI) are used in postmortem radiological investigation of cardiovascular pathologies. This review presents the actual state of postmortem imaging for cardiovascular pathologies in cases of sudden cardiac death (SCD), taking into consideration both the advantages and limitations. The radiological evaluation of ischemic heart disease (IHD), the most frequent cause of SCD in the general population of industrialized countries, includes the examination of the coronary arteries and myocardium. Postmortem CT angiography (PMCTA) is very useful for the detection of stenoses and occlusions of coronary arteries but less so for the identification of ischemic myocardium. MRI is the method of choice for the radiological investigation of the myocardium in clinical practice, but its accessibility and application are still limited in postmortem practice. There are very few reports implicating postmortem radiology in the investigation of other causes of SCD, such as cardiomyopathies, coronary artery abnormalities, and valvular pathologies. Cardiomyopathies representing the most frequent cause of SCD in young athletes cannot be diagnosed by echocardiography, the most widely available technique in clinical practice for the functional evaluation of the heart and the detection of cardiomyopathies. PMCTA and MRI have the potential to detect advanced stages of diseases when morphological substrate is present, but these methods have yet to be sufficiently validated for postmortem cases. Genetically determined channelopathies cannot be detected radiologically. This review underlines the need to establish the role of postmortem radiology in the diagnosis of SCD.

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Staphylococcus aureus is a highly successful pathogen responsible of a wide variety of diseases, from minor skin infection to life-threatening sepsis or infective endocarditis, as well as food poisoning and toxic shock syndrome. This heterogeneity of infections and the ability of S. aureus to develop antibiotic-resistance to virtually any available drugs reflect its extraordinary capacity to adapt and survive in a great variety of environments. The pathogenesis of S. aureus infection involves a wide range of cell wall-associated adhesins and extracellular toxins that promote host colonization and invasion. In addition, S. aureus is extremely well equipped with regulatory systems that sense environmental conditions and respond by fine tuning the expression of metabolic and virulence determinants. Surface adhesins referred to MSCRAMMs - for Microbial Surface Component Recognizing Adherence Matrix Molecules - mediate binding to the host extracellular matrix or serum components, including fibrinogen, fibronectin, collagen and elastin, and promote tissue colonization and invasion. Major MSCRAMMs include a family of surface-attached proteins covalently bound to the cell wall peptidoglycan via a conserved LPXTG motif. Genomic analyses indicate that S. aureus contain up to 22 LPXTG surface proteins, which could potentially act individually or in synergy to promote infection. In the first part of this study we determined the range of adherence phenotypes to fibrinogen and fibronectin among 30 carriage isolates of S. aureus and compared it to the adherence phenotypes of 30 infective endocarditis and 30 blood culture isolates. Overall there were great variations in in vitro adherence, but no differences were observed between carriage and infection strains. We further determined the relation between in vitro adherence and in vivo infectivity in a rat model of experimental endocarditis, using 4 isolates that displayed either extremely low or high adherence phenotypes. Unexpectedly, no differences were observed between the in vivo infectivity of isolates that were poorly and highly adherent in vitro. We concluded that the natural variability of in vitro adherence to fibrinogen and fibronectin did not correlate with in vivo infectivity, and thus that pathogenic differences between various strains might only be expressed in in vivo conditions, but not in vitro. Therefore, considering the importance of adhesins expression for infection, direct measurement of those adhesins present on the bacterial surface were made by proteomic approach. 5 In the second series of experiments we assessed the physical presence of the LPXTG species at the staphylococcal surface, as measured at various time points during growth in different culture media. S. aureus Newman was grown in either tryptic soy broth (TSB) or in Roswell Park Memorial Institute (RPMI) culture medium, and samples were removed from early exponential growth phase to late stationary phase. Experiments were performed with mutants in the global accessory-gene regulator (agr), surface protein A (Spa) and clumping factor A (ClfA). Peptides of surface proteins were recovered by "trypsin-shaving" of live bacteria, and semi-quantitative proteomic analysis was performed by tandem liquid-chromatography and mass-spectrometry (LC-MS). We also determined in parallel the mRNA expression by microarrays analysis, as well as the phenotypic adherence of the bacteria to fibrinogen in vitro. The surface proteome was highly complex and contained numerous proteins theoretically not belonging to the bacterial envelope, including ribosomal proteins and metabolic enzymes. Sixteen of the 21 known LPXTG species were detected, but were differentially expressed. As expected, 9 known agr-regulated proteins (e.g. including Spa, FnBPA, ClfA, IsdA, IsdB, SasH, SasD, SasG and FmtB) increased up to the late exponential growth phase, and were abrogated in agr-negative mutants. However, only Spa and SasH modified their proteomic and mRNA profiles in parallel in the parent and its agr negative mutant, while all other LPXTG proteins modified their proteomic profiles independently of their mRNA. Moreover, ClfA became highly transcribed and active in in vitro fibrinogen adherence tests during late growth (24h), whereas it remained poorly detected by proteomics. Differential expression was also detected in iron-rich TSB versus iron-poor RPMI. Proteins from the iron-regulated surface determinant (isd) system, including IsdA, IsdB and IsdH were barely expressed in iron-rich TSB, whereas they increased their expression by >10 time in iron-poor RPMI. We conclude that semi-quantitative proteomic analysis of specific protein species is feasible in S. aureus and that proteomic, transcriptomic and adherence phenotypes demonstrated differential profiles in S. aureus. Furthermore, peptide signatures released by trypsin shaving suggested differential protein domain exposures in various environments, which might be relevant for antiadhesins vaccines. A comprehensive understanding of the S. aureus physiology should integrate all these approaches.

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Historical references to the emergence of the current concept of ADHD typically cite descriptions from medical textbooks by Weikard (1775) and Crichton (An inquiry into the nature and origin of mental derangement: Comprehending a concise system of the physiology and pathology of the human mind and a history of the passion and their affects. Cardell Jr and Davies, Londres, 1798) on attention disorders, poems of Hoffman on hyperactive and impulsive behaviors (Der Struwwelpeter. Frankfurt am Main, Literarische Anstalt, 1843), as well as the work of Still (Lancet 1:1008-1012, 1077-1082, 1163-1168, 1902a, Lancet 159(4102):1008-1013, 1902b, Lancet 159(4103):1077-1082, 1902c, Lancet 159(4104):1163-1168, 1902d) on impulsive behaviors and defective moral regulation of behavior. The notion of "instability" developed by French physicians between 1887 and 1910 is rarely mentioned and often ignored. Writings from this period show that in France, the emergence of the concept of ADHD according to modern terminology comes from the notion of "mental instability" introduced in the 1890s under the leadership of Désiré-Magloire Bourneville at the Hospital Bicêtre in Paris, based on his observations of children and adolescents who had been labeled "abnormal" and placed in medical and educational institutions. In the early twentieth century, elaborating on the observations of Bourneville, Jean Phillipe and Georges Paul-Boncour showed the presence of a subgroup of "unstable" children who suffered from a disease entity in its own right within the population of "abnormal" schoolchildren (the terminology of the time). This new pathological entity included symptoms of hyperactivity, impulsivity and inattention, corresponding to today's classic triad of ADHD symptoms. While noting the lack of behavioral inhibition, clinical descriptions of Bourneville, Philip and Paul-Boncour also considered the notion of "moral disorder" which at that time played an important role in psychopathology. This resulted in some degree of confusion between impulsive symptoms and major behavioral disturbances often associated with ADHD.