De novo development of small cyclic peptides that are orally bioavailable.

Cyclic peptides can bind challenging disease targets with high affinity and specificity, offering enormous opportunities for addressing unmet medical needs. However, as with biological drugs, most cyclic peptides cannot be applied orally because they are rapidly digested and/or display low absorption in the gastrointestinal tract, hampering their development as therapeutics. In this study, we developed a combinatorial synthesis and screening approach based on sequential cyclization and one-pot peptide acylation and screening, with the possibility of simultaneously interrogating activity and permeability. In a proof of concept, we synthesized a library of 8,448 cyclic peptides and screened them against the disease target thrombin. Our workflow allowed multiple iterative cycles of library synthesis and yielded cyclic peptides with nanomolar affinities, high stabilities and an oral bioavailability (%F) as high as 18% in rats. This method for generating orally available peptides is general and provides a promising push toward unlocking the full potential of peptides as therapeutics.

Predictive factors for the outcome of emotional and/or behavioural disorders in 18- to 48-month-old children after parent-child psychotherapy: Protocol of a European prospective cohort study.

OBJECTIVES: Several studies have shown that in young children, behavioural and/or emotional disorders are more difficult to manage than regulatory disorders. Moreover, data are lacking on outcome predictive factors. This article presents a short synthesis of previous research about outcome predictive factors in child psychiatry. It also describes the protocol of a longitudinal observational European multicentre study the main objective of which was to identify predictive factors of behavioural and emotional disorder outcome in toddlers after parent-child psychotherapy. The secondary objectives were to study predictive factors of the outcome in parents (anxiety/depression symptoms) and parent-child relationship. METHOD: In order to highlight medium-effect size, 255 toddlers (age: 18 to 48 months) needed to be included. Outcomes will be assessed by comparing the pre- and post-therapy scores of a battery of questionnaires that assess the child's symptoms, the parents' anxiety/depression, and the parent-child relationship. Multivariate linear regression analysis will be used to identify predictive factors of the outcome among the studied variables (child age and sex, socio-economic status, life events, disorder type, intensity and duration, social support, parents' psychopathology, parents' attachment, parent-child relationships, therapy length and frequency, father's involvement in the therapy, and therapeutic alliance). EXPECTED RESULTS AND CONCLUSION: This study should allow identifying some of the factors that contribute to the outcome of externalizing and internalizing disorders, and distinguishing between pre-existing and treatment-related variables. It should also help to identify children at higher risk of poor outcome who require special vigilance on the part of the therapist. It should confirm the importance of therapeutic alliance. TRIAL REGISTRATION: ID-RCB 2008-A01088-47.

Adaptation of the working alliance inventory to therapeutic interventions for early-age regulatory and behavioral symptoms: French versions of the infant-toddler WAI for parents and therapists.

OBJECTIVES: The therapeutic alliance, an essential component of the therapeutic process, has been investigated in adult and child therapy, but studies in the context of parent-infant or parent-toddler therapeutic interventions are scarce. This monocentric study aims to produce a French cross-cultural adaptation of a therapeutic alliance scale for the context of early consultations in a child and psychiatry department. METHOD: Fifty-five young children aged 3 to 30 months consulting for regulation or behavioral disorders and their mothers were included in the study. The working alliance inventory (WAI) was translated into French by two bilingual translators and adapted to early-age consultations in parent and therapist versions. Assessments of the child's symptoms and the parents' anxiety and depression were carried out at the start and end of therapy. We studied the association of the alliance with the initial clinical characteristics and with the outcome of the child and the mother. An exploratory factor analysis was performed considering the items most associated with expected outcomes. RESULTS: The alliance coded by the mother was lower in case of child behavioral problems and was associated with the mother and child outcome. Short versions of the infant-toddler WAI were developed based on factor analysis, highlighting four factors: positive goals and tasks, bond with the mother, alliance with the child, negative experience of care relationship. DISCUSSION: Results were similar to those found in therapy with adults or older children. The alliance issue in mother-baby therapies was as essential as in other therapy contexts. The short Infant-Toddler WAI resulting from this work must be validated in future studies.

Mexican population sub-analysis of the lixilan clinical program with the fixed ratio combination of insulin glargine and lixisenatide (iGlarLixi).

AIM: To evaluate the efficacy and safety of iGlarLixi in Mexican patients with type 2 diabetes who participated in the LixiLan clinical trials and compare results with the rest of the patients. METHODS: Data was collected for Mexican patients who participated in either of three studies: phase 2 trial LixiLan-POC, that compared iGlarLixi vs insulin glargine (iGlar) on inadequately controlled patients with metformin; phase 3 trial LixiLan-O, comparing iGlarLixi vs iGlar and lixisenatide on inadequately controlled patients with oral antidiabetic agents; and finally the phase 3 trial LixiLan-L, comparing iGlarLixi vs iGlar on inadequately controlled patients with basal insulin. The primary endpoint was the change in HbA1c from baseline to end of treatment. RESULTS: In the Mexican population, treatment with iGlarLixi significantly improved HbA1c compared with each component alone achieving an average of 6.5%; (6.17%, 6.63% and 6.73% for the LixiLan-POC, O and L studies respectively) and an average HbA1c reduction from baseline of 1.6%, for the three studies at end of treatment period. CONCLUSION: The efficacy and safety profile of iGlarLixi demonstrate a fair or better composite endpoint of HbA1c without hypoglycemia and no weight gain compared to overall trial population, which could help improve Mexican patients' outcomes.

Listeria monocytogenes-associated respiratory infections: a study of 38 consecutive cases.

OBJECTIVES: Listeria monocytogenes (Lm) is a foodborne human pathogen responsible for severe infections, including septicaemia, neurolisteriosis, and maternal-foetal and focal infections. Little is known about Lm-associated respiratory tract or lung infections. METHODS: We conducted a retrospective study of culture-proven cases of Lm pleural infections and pneumonia reported to the French National Reference Centre for Listeria from January 1993 to August 2016. RESULTS: Thirty-eight consecutive patients with pleural infection (n = 32), pneumonia (n = 5), or both (n = 1) were studied; 71% of these were men. Median age was 72 (range 29-90). Two patients presented with concomitant neurolisteriosis. All patients but one reported at least one immunosuppressive condition (97%), with a median number of 2 (range 0-5), including 29% (8/28) with current exposure to immunosuppressive therapy and 50% (17/34) with ongoing neoplasia; 75% (21/28) reported previous pleural or pulmonary disease. Antibiotic therapy mostly consisted in amoxicillin (72%) associated with aminoglycoside in 32%. Chest-tube drainage was performed in 7/19 patients with empyema (37%); 25% of the patients (7/30) required intensive care management. In-hospital mortality reached 35% and occurred after a median time interval of 4 days (range 1-33 days). Three patients had recurrence of empyema (time interval of 1 week to 4 months after treatment completion). Altogether, only 13/31 patients (42%) diagnosed with Lm respiratory infection experienced an uneventful outcome at 2-year follow-up. CONCLUSION: Lm is a rare but severe cause of pneumonia and pleural infection in older immunocompromised patients, requiring prompt diagnosis and adequate management and follow-up.

Infrared low-level diode laser on serum chemokine MCP-1 modulation in mice.

The effect of the low-level laser therapy (LLLT) in the modulation of cells related to inflammatory processes has been widely studied, with different parameters. The objective was to investigate the immediate and cumulative effect of infrared LLLT on chemokine monocyte chemotactic protein-1 (MCP-1) modulation in mice. Fifty-two isogenic mice were distributed in seven groups: control (n = 10, no surgical procedure), laser I (n = 7, surgical procedure and a single LLLT exposure 12 h after the surgery), laser II (n = 7, surgery followed by two LLLT exposures, 12 and 36 h after surgery), and laser III (n = 7, surgery followed by three LLLT exposures, 12, 36, and 60 h after surgery). For each group, a sham group (n = 21) underwent surgery without laser application. The animals in the laser groups received an infrared diode continuous laser exposure (AsGaAl, 780 nm wavelength, power of 20 mW, energy density of 10 J/cm(2), spot size of 0,04 cm(2)) on three points (20 s per point), and a final energy of 0.4 J. The animals were sacrificed 36 h (laser I and sham I groups), 60 h (laser II and sham II), and 84 h (laser III and sham III groups) after surgery. The MCP-1 concentrations were measured by cytometric bead array. There was no significant difference between the three periods in the sham group (p = 0.3). There was a lower concentration of MCP-1 in the laser III group compared to the laser I group (p = 0.05). The infrared LLLT showed a cumulative effect in the modulation of chemokine MCP-1 concentration. Three LLLT exposures were necessary to achieve the MCP-1 modulation.

[Infants and toddlers behavioral and functional disorders: characteristics, mother-child interactions, alliance and outcome after a brief parents-child psychotherapy. A pilot study]. / Troubles du comportement et troubles fonctionnels du nourrisson : caractéristiques, interactions mère-enfant, alliance et évolution après une psychothérapie brève parent-enfant. Étude pilote.

OBJECTIVES: Functional and behavioral disorders are the most frequent reasons for consultation in infant psychiatry, but there are still few studies about the efficacy of parents-child psychotherapies. Functional disorders appear to be easier to treat than behavioral disorders. The aim of this study was: (1) to assess outcome after a brief psychotherapy in a population of 49 infants aged 3 to 30 months, presenting functional or behavioral disorders; (2) to compare characteristics before therapy and outcomes for children with functional disorders and with behavioral disorders, to have a better understanding of the worse outcome of children with behavioral disorders. METHODS: Two assessments were performed, one before treatment and the second a month after the end of the therapy including the infant's symptoms (Symptom Check-list), parents' anxious and depressive symptoms (Hospital Anxiety and Depression scale) and mother-infant interactions (Crittenden Experimental Index of adult-infant relationship). The therapeutic alliance was assessed by the therapist and the parents after the first consultation (Working Alliance Inventory). RESULTS: The assessments after therapy show complete or partial improvement in the child's symptoms, in the mother's anxious and depressive symptoms and in the father's anxious symptoms. During interaction, the mothers become more sensible, the number of controlling and of unresponsive mothers decrease, while the children become more cooperative and less passive. Initial characteristics and outcome are however different according to the type of the child's disorder. The children with behavioral disorders are older and present an association of several symptoms. The disorder onset is later. Their mothers are, before therapy, more anxious and depressive. The therapeutic alliance is weaker. After therapy, despite the fact that their mothers' affective state and that interactive behavior improves, the mothers are more anxious and less sensible, while the children no longer differ from the group without behavioral disorder from the point of view of opposition (assessed during mother-child interaction). CONCLUSION: Although this study is limited by the lack of a control group and the sample size, it underlines some particularities of infants and toddlers presenting behavioral disorders and the difficulties involved in their treatment. One can wonder if these characteristics are specific of the behavioral disorders or if they are the result of an older dysfunction, complicated by the developmental evolution of the child and the duration of the difficulties. The small number of cases, among the children with behavioral disorders, presenting a preexistent functional disorder, the absence of difference in the duration of the disorders, and the different disorder's onset plead in favor of the first hypothesis. The behavioral disorders often associate child psychopathology, dysfunctional parents-child-relationships and environmental factors difficult to modify with a brief therapy focused on the relationship. It would appear necessary to develop specific treatments for this population.

Infrared low-level diode laser on inflammatory process modulation in mice: pro- and anti-inflammatory cytokines.

To evaluate the modulation of proinflammatory (interleukin-6, IL-6; tumor necrosis factor-α, TNF-α; and interferon-γ, IFN-γ) and anti-inflammatory cytokines (transforming growth factor-ß1, TGF-ß1) in the inflammation processes in vivo with low-level laser action, 50 isogenic mice were randomly distributed into three groups: control (no surgical procedure, n = 10), sham (surgical procedure with three standard cutaneous incisions, followed by an abdominal muscle incision and suture, n = 20), and laser (same procedure followed by laser exposure, n = 20). The sham group was divided into three subgroups: sham I (euthanasia and evaluation, 36 h after surgical procedure), sham II (euthanasia and evaluation, 60 h after surgical procedure), and sham III (euthanasia and evaluation, 84 h after surgical procedure). The laser group was also divided in three subgroups: laser I (a single laser session, 12 h after surgery), laser II (two laser sessions, 12 and 36 h after surgery), and laser III (three laser sessions, 12, 36, and 60 h after surgery). All animals in the laser groups received three points per session of continuous infrared laser (wavelength of 780 nm, power of 20 mW, fluency of 10 J/cm(2), exposure time of 20 s per point, and energy of 0.4 J). After euthanasia, spleen mononuclear cells were isolated and cultured for 48 h. Concentrations of IL-6, TNF-α, IFN-γ, and TGF-ß1 were obtained by enzyme-linked immunosorbent assay method. There was a significant difference between the IL-6 and TNF-α concentrations in the 60-and 84-h evaluations when the laser and sham groups were compared to the control group (p < 0.05), except for laser II in the TNF-α analysis (p > 0.05). The IFN-γ concentration analysis showed a significant difference only in sham II when compared to the control group (p < 0.05). Thus, there was a modulatory effect of TNF-α and IFN-γ in the laser group, particularly in the 60-h postoperative evaluation. There was no significant difference between the laser, sham, and control groups for TGF-ß1 analysis (p > 0.05). The low-level laser application decreased the TNF-α and IFN-γ release in vivo of spleen mononuclear cells in mice, especially after two exposure sessions. However, there was no modulation of the IL-6 and TGF-ß1 release.

Calibration of low-level laser therapy equipment.

BACKGROUND: Despite the increase in the use of low-level laser therapy (LLLT), there is still a lack of consensus in the literature regarding how often the equipment must be calibrated. OBJECTIVE: To evaluate the real average power of LLLT devices in the Greater São Paulo area. METHODS: For the evaluation, a LaserCheck power meter designed to calibrate continuous equipment was used. The power meter was programmed with data related to the laser's wavelength to gauge the real average power being emitted. The LLLT devices were evaluated in two ways: first with the device cooled down and then with the device warmed up for 10 minutes. For each condition, three tests were performed. The laser probe was aligned with the power meter, which provided the real average power being emitted by the LLLT device. All of the data and information related to the laser application were collected with the use of a questionnaire filled in by the supervising therapists. RESULTS: The 60 devices evaluated showed deficit in real average power in the cooled-down and warmed-up condition. The statistical analysis (ANOVA) showed a significant decrease (p<0.05) in the real average power measured in relation to the manufacturer's average power. On average, the most common dose in the clinics was 4 J/cm², and the most desired effects were healing and anti-inflammatory effects. According to the World Association for Laser Therapy (WALT), 1 to 4 J of final energy are necessary to achieve these effects, however only one device was able to reach the recommended therapeutic window. CONCLUSION: The LLLT devices showed a deficit in real average power that emphasized a lack of order in the application of this tool. The present study also showed the need for periodical calibration of LLLT equipment and a better technical knowledge of the therapists involved.

Aferição dos equipamentos de laser de baixa intensidade / Calibration of low-level laser therapy equipment

CONTEXTUALIZAÇÃO: A laserterapia de baixa intensidade (LBI) vem sendo cada vez mais utilizada, porém ainda não há consenso na literatura quanto ao tempo em que os equipamentos devem ser submetidos à aferição ou calibragem. OBJETIVO: Analisar a potência média real (PmR) dos equipamentos de LBI na região da Grande São Paulo. MÉTODOS: Para análise dos equipamentos, utilizou-se um potenciômetro (Lasercheck), próprio para aferição de equipamentos contínuos, o qual foi programado com dados referentes ao comprimento de onda do laser a ser avaliado, obtendo-se assim a PmR emitida. Os equipamentos foram analisados de duas formas: uma, com o LBI desaquecido, e outra, após 10 minutos de uso (aquecido), sendo que três análises foram feitas para cada condição. A caneta emissora foi acoplada ao potenciômetro, o qual fornecia a PmR emitida pelo LBI. Todos os dados e informações referentes à aplicação do laser foram coletados por um questionário respondido pelos responsáveis. RESULTADOS: Os 60 equipamentos avaliados mostraram déficit na PmR com os equipamentos desaquecidos e aquecidos. A análise estatística (ANOVA) mostrou diminuição significativa (P<0,05) da PmR aferida em relação à potência média do fabricante (PmF). Em média, a dose mais empregada nas clínicas foi de 4 J/cm², tendo os efeitos de cicatrização e anti-inflamatório como os mais desejados. Segundo a World Association for Laser Therapy (WALT), para atingir esse efeito, necessita-se de 1 a 4 J de energia final, sendo que apenas um dos 60 aparelhos conseguiria atingir a janela terapêutica preconizada. CONCLUSÃO: Os equipamentos de LBI apresentam um déficit acentuado na PmR, o que mostra uma desordem na utilização desse recurso. Neste estudo, observou-se a necessidade de aferição periódica dos aparelhos de LBI bem como melhor conhecimento técnico dos profissionais envolvidos.

BACKGROUND: Despite the increase in the use of low-level laser therapy (LLLT), there is still a lack of consensus in the literature regarding how often the equipment must be calibrated. OBJECTIVE: To evaluate the real average power of LLLT devices in the Greater São Paulo area. METHODS: For the evaluation, a LaserCheck power meter designed to calibrate continuous equipment was used. The power meter was programmed with data related to the laser's wavelength to gauge the real average power being emitted. The LLLT devices were evaluated in two ways: first with the device cooled down and then with the device warmed up for 10 minutes. For each condition, three tests were performed. The laser probe was aligned with the power meter, which provided the real average power being emitted by the LLLT device. All of the data and information related to the laser application were collected with the use of a questionnaire filled in by the supervising therapists. RESULTS: The 60 devices evaluated showed deficit in real average power in the cooled-down and warmed-up condition. The statistical analysis (ANOVA) showed a significant decrease (p<0.05) in the real average power measured in relation to the manufacturer's average power. On average, the most common dose in the clinics was 4 J/cm², and the most desired effects were healing and anti-inflammatory effects. According to the World Association for Laser Therapy (WALT), 1 to 4 J of final energy are necessary to achieve these effects, however only one device was able to reach the recommended therapeutic window. CONCLUSION: The LLLT devices showed a deficit in real average power that emphasized a lack of order in the application of this tool. The present study also showed the need for periodical calibration of LLLT equipment and a better technical knowledge of the therapists involved.

Single session to infrared low level diode laser on TNF-alpha and IL-6 cytokines release by mononuclear spleen cells in mice: a pilot study.

BACKGROUND AND OBJECTIVE: The results of low-level infrared laser (LLL) systemic action on inflammatory modulation process, specifically diminishing pro-inflammatory and producing anti-inflammatory cytokines are extremely controversial in the literature. More studies are necessary to clarify the biomodulation process. The main objective was to investigate the effect of a single session of an AsGaAl laser on spleen cells interleukin-6 (IL-6) and tumor necrosis factor - alpha (TNF-alpha) release, in vivo, in mice. STUDY DESIGN/MATERIALS AND METHODS: In a pilot study, 18 isogenic mice were distributed in three groups: control (no surgical procedure, n = 6), sham (surgical procedure with three standard cutaneous incisions, followed by abdominal muscle incision followed by suture, n = 6) and LLL (same procedure followed by a single LLL exposure 12 hours after the procedure, n = 6). The animals in the LLL group received a single infrared continuous laser session (780 nm wavelength, power of 20 mW, energy density of 10 J/cm(2)) on three points (20 seconds per point), and final energy of 0.4 J. All animals of the sham and LLL groups were sacrificed 36 hours after surgical procedure; the spleen mononuclear cells were isolated and cultivated for 48 hours. The IL-6 and TNF-alpha were measured by the ELISA method. RESULTS: IL-6 and TNF-alpha concentrations released by the mononuclear cells showed significant differences between the control and sham group (P < 0.07). However, there were no differences between the control and LLL group and between the sham and LLL groups (P > 0.07). CONCLUSION: The single session of infrared LLL showed a tendency of decreasing the IL-6 and TNF-alpha release by mononuclear spleen cells in mice after application, although there was not a significant difference between the sham and LLL group. Conclusions regarding effectiveness of a single session procedure cannot be made due to the low statistical power of this pilot study.

[ADHD and attachment processes: are they related?]. / Trouble déficit de l'attention/hyperactivité (TDAH) : quels liens avec l'attachement ?

Attention-deficit/hyperactivity disorder (ADHD) is defined on the basis of developmentally inappropriate inattention, motor activity and impulsivity that emerges early in development and causes impairment in social and academic functioning. ADHD is described as a multifactorial disease, with a well studied genetic vulnerability, and early environmental factors also playing an important role in the development and course of the disorder. Current aetiological models emphasize interaction between genes and environment. The concept of attachment, as proposed by John Bowlby, reflects quality of early interactions, and should therefore be considered as an early developmental factor. First, clinical findings emphasize similitude between both disorders; emotional dysregulation is an important feature in reactive attachment disorder as well as in ADHD. Emotion regulation is highly related to attachment security in young children and could play a part in the development of early attention processes. Moreover, difficult temperament is associated with higher risk for ADHD on the one hand, and can disturb the process of attachment on the other. Parental caregiving - including maternal sensitivity, positive parenting practices - is a main factor involved in the development of attachment, and has shown to be associated with better outcomes in ADHD children, especially with less oppositional/conduct disorders. Second, the aim of our review is to present clinical studies that have looked for a link between ADHD and attachment: the type of attachment could play a part in the course of the disorder: insecure and disorganised attachment types tend to be associated with a higher risk of externalised behaviors in children. For ADHD, this effect seems to be weaker than for other externalised disorders, and has been shown only in populations of at-risk children. Clinical studies also raise the question of possible links between reactive attachment disorder and ADHD. In children suffering severe early deprivon such as institution-rearing, inattention/hyperactivity symptoms were shown to be high, but these findings may not be valid in less severely deprived children. Third, another link could depend on a common vulnerability for ADHD and attachment disorder. Some perinatal factors, such as smoking during pregnancy or prematurity, have been shown to increase the risk of hyperactive symptoms in children. These variables may also be associated with a higher risk of impaired early interactions. Recent animal studies have raised interest in the role of prenatal stress in the emotional and behavioral development of the offspring, particularly as regards vulnerability to stress. Epigenetic mechanisms may be involved in durable alterations of the hypothalamo-pituitary-adrenergic axis. Preliminary findings in humans show that prenatal stress or maternal depression may also influence the development of the child. The understanding of the relationship between attachment and ADHD may help to better target prevention and intervention efforts. As the perinatal period seems to be particularly involved in both ADHD and attachment disorders, early guidance and possibly prenatal interventions should be developed and assessed for mothers and caregivers with risk-factors.

Predictors of outcome in infant and toddlers functional or behavioral disorders after a brief parent-infant psychotherapy.

The efficacy of parent-child psychotherapies is widely recognized today. There are, however, less data on predictive factors for outcome in infants and toddlers and their parents. The aim of this study was to highlight predictive factors for outcome after a brief psychotherapy in a population of 49 infants and toddlers aged 3-30 months presenting functional or behavioral disorders. Two assessments were performed, the first before treatment and the second a month after the end of the therapy. These assessments included an evaluation of the child's symptoms, and of depressive or anxiety symptoms in the parents. The assessments after therapy show complete or partial improvement in the child's symptoms for nearly three quarters, and a decrease in the number of anxious and depressive mothers, and also in the number of depressive fathers. Three independent factors appear as predictive of unfavorable outcome for the child: frequency and intensity of behavioral problems and fears, and the absence of the father at more than two-thirds of consultations. The outcome for the mother is associated solely with her anxiety score at the start of the therapy. This study underlines the particular difficulties involved in the treatment of infants and toddlers presenting behavioral disturbances and emotional difficulties, and the value of involving the father in treatment.

Triadic nonverbal communication in mother-infant consultations: Two contrasted cases.

The aim of the present case study was to present and discuss the analysis of triadic nonverbal communication between mother, infant, and therapist in two early consultations as an indicator of the therapeutic alliance. The analysis explored nonverbal triadic interactions (body positions and facial orientations of the mother, infant, and therapist, and expressive behaviors of the infant) and triadic affective sharing (via a microanalytic interview of the therapist). The quality of the therapeutic alliance and clinical outcome for each case are described. The description of the two cases illustrates the importance of the progressive development of nonverbal "engagement" by the three people (triadic alliance) and of moments with triadic emotional sharing. The contribution of the therapist appears to be crucial, in particular via his or her body and affective engagement with the infant. The triadic alliance appears to be both an indicator of the therapeutic alliance and an element that can foster it.

Deficient in vitro anti-mycobacterial immunity despite successful long-term highly active antiretroviral therapy in HIV-infected patients with past history of tuberculosis infection or disease.

We evaluated the anti-Mycobacterium tuberculosis (Mtb) immune responses of HIV patients after long-term successful HAART, presenting >500 TCD4+ cells/microl, undetectable viral load, and past history of tuberculosis infection (HIV+PPD+, n=14) or disease (HIV+CTB, n=17). Their lymphoproliferative and IFN-gamma responses were compared with those from HIV-uninfected controls either PPD+ (HIV-PPD+, n=17) or with past history of pulmonary tuberculosis (n=15). Most HIV-infected patients presented normal PHA responses while responses to the Mtb recombinant polypeptides ESAT-6 and Ag85B were markedly reduced. Responses to a whole Mtb lysate (S-Mtb) in HIV+PPD+ patients were lower than in HIV-PPD+ controls, while in HIV+CTB patients these responses were similar to that of past-tuberculosis controls. Comparison between the two HIV groups also suggested better S-Mtb responses in those cured from tuberculosis. Thus, while immune responses to single Mtb proteins are depressed even after successful HAART, reactivity to S-Mtb is high, specially in those cured from tuberculosis, possibly as a result of the survival of higher numbers of mycobacteria-specific T cell clones during the immunosuppression phase, which may afford sufficient protection against new Mtb challenges.

Manduca sexta allatotropin and the in vitro biosynthesis of juvenile hormone by moth corpora allata: a comparison of Pseudaletia unipuncta females from two natural populations and two selected lines.

We compared the effects of Manduca sexta allatotropin (Manse-AT) on the rate of in vitro juvenile hormone (JH) biosynthesis by the corpora allata (CA) of different-aged virgin females from migrant (Quebec) and non-migrant (Azores) populations of the armyworm, Pseudaletia unipuncta, as well as from early- and late-calling lines selected from the Quebec population. There was a significant age x strain interaction, with the observed rates of JH biosynthesis in early adult life closely reflecting strain-specific differences in the age at onset of calling. In considering data for all ages combined, treatment of CA with Manse-AT resulted in a significant increase in the rate of JH biosynthesis for all but the Late strain, although significant differences for this strain were detected at certain ages. The CA of females from the Azores strain showed the strongest stimulation, with those of 0- and 1-day-old individuals displaying a singularly high degree of sensitivity. Selection for early- and late-calling lines resulted in significant differences in the temporal patterns of JH biosynthesis but did not markedly affect the sensitivity of the CA to Manse-AT. These findings are discussed within the context of the age-related differences observed in the rates of in vitro JH biosynthesis and JH haemolymph titers previously reported in comparisons of the Quebec and Azorean strains of the true armyworm.

Social stigma: a comparative qualitative study of integrated and vertical care approaches to leprosy.

Integration of leprosy into the general health system is very much emphasized by health care planners. One prime reason stated for this is to reduce stigma attached to this disease. This study was conducted in the state of Maharashtra, India, to compare the level of social stigma towards leprosy in communities with a vertical and an integrated programme. The data were collected in three areas of five villages each. The first two areas were in an integrated programme to test for internal consistency and the third in a vertical programme. All the leprosy patients with visible deformities in these villages were enrolled in the study, and an in-depth stigma measurement scale was administered. In addition, focus group discussions were conducted among the family members of leprosy patients and participative rural appraisal was done in the communities. The data were analysed using qualitative methods. A total of 24 leprosy patients with visible deformities participated in the in-depth stigma measurement exercise from 15 villages. Fifteen focus group discussions were conducted with families of leprosy patients and an equal number of participatory rural appraisals with communities were done. The results show that social stigma was virtually non-existent among the communities with the integrated approach and minimally experienced by leprosy patients in this model. However, a high level of self-stigmatization among leprosy patients was observed in the vertical approach and equally a high level of social stigma was found in their communities, which led to reduced interaction between the leprosy patients and their communities. The integrated approach to community-based primary health care is effective in reducing leprosy stigma in society.