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BACKGROUND Increasing interest has centred on the psychotherapeutic working alliance as a means of understanding clinical change in digital mental health interventions in recent years. However, little is understood about how and to what extent a digital mental health program can have an impact on the working alliance and clinical outcomes in a blended (therapist plus digital program) cognitive behavioural therapy (bCBT) intervention for depression. OBJECTIVE To test the difference in working alliance scores between bCBT and treatment-as-usual (TAU); examine association between working alliance and depression severity scores in both arms; and test for an interaction between system usability and working alliance, on the association between the working alliance and depression scores in bCBT at 3-month assessments. METHODS A secondary data analysis from a non-inferiority trial comparing bCBT with TAU across nine European countries was conducted. Data were collected in primary care and specialised services across nine European countries between April 2015 and December 2017. Eligible participants aged 18 years or older and diagnosed with major depressive disorder were randomized to either bCBT (n=476) or TAU (n=467). bCBT consisted of 6-20 sessions of bCBT (involving face-to-face sessions with a therapist and an internet-based program). TAU consisted of usual care for depression. The main outcomes were scores on working alliance (measured by Working Alliance Inventory-Report Form-Client (WAI-SR-C)); depressive symptoms (Patient Health Questionnaire-9 (PHQ-9)), at 3-months. Other variables included system usability scores (System Usability Scale-Client (SUS-C)) at 3-months and demographic information collected at baseline. Data from baseline and 3-month assessments were analysed using generalized linear regression models that adjusted for a set of baseline variables. RESULTS Of the 945 participants, 644 (68%) were female, and the mean age was 38.96 years (IQR=38). bCBT was associated with higher composite WAI-SR-C scores compared to TAU (unstandardised coefficients beta [95% CI]: 5.67 [4.48-6.86]). Higher WAI-SR-C composite scores were associated with a significant decrease in PHQ-9 scores in bCBT (e.g., composite scores: -0.12 [-0.17 to -0.06]) and in TAU (e.g., composite scores: -0.06 [-0.11 to -0.02]). Finally, there was a significant interaction of SUS-C and WAI-SR-C, on an inverse association between higher WAI-SR-C scores and lower PHQ-9 scores in bCBT (b= -0.030, [95% CI: -0.05 to -0.01] P=0.005]). CONCLUSIONS To our knowledge, this is the first study to show that bCBT may enhance the client working alliance when compared to evidence-based routine care for depression. The working alliance in bCBT was also associated with clinical improvements, that appear to be enhanced by good program usability. Our findings add further weight to the view that the addition of iCBT to face-to-face CBT, can positively augment experiences of the working alliance. CLINICALTRIAL France: ClinicalTrials.gov NCT02542891. Registered on 4 September 2015; Germany: German Clinical Trials Register DRKS00006866. Registered on 2 December 2014; The Netherlands: Netherlands Trials Register NTR4962. Registered on 5 January 2015; Poland: ClinicalTrials.Gov NCT02389660. Registered on 18 February 2015; Spain: ClinicalTrials.gov NCT02361684. Registered on 8 January 2015; Sweden: ClinicalTrials.gov NCT02449447. Registered on 30 March 2015; Switzerland: ClinicalTrials.gov NCT02410616. Registered on 2 April 2015; United Kingdom: ISRCTN registry, ISRCTN12388725. Registered on 20 March 2015. Denmark: ClinicalTrials.gov NCT02796573. Registered 1st June 2016. INTERNATIONAL REGISTERED REPORT RR2-https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-016-1511-1

In all times, humankind has used several species of the genus Allium as food, spice, or herbal remedy. Some of these species have been cultivated, such as garlic (Allium sativum) or onion (Allium cepa). Today, their value for human health care is one of the most important aims of research. Up to now, many applications of Allium species are known for the use of phyto-pharmaceutical preparations. Therefore, the present study aimed to determine the phytochemical profile of cultivated garlic (Allium sativum), and red onion (Allium cepa) in Algeria, both quantitatively (total phenolic, total flavonoids, condensed and hydrolysable tannins contents) and qualitatively (phytochemical screening), to characterize the phenolic compounds using HPLC method and to evaluate the antioxidant properties using DPPH assay. Red onion gave the higher amounts of total phenolic compounds (86±1.00mg GAE/100g DM), flavonoids (43.33±0.57mg QE/100 g DM), condensed tannins (4.4±0.52 mg CE/100g DM) and hydrolyzable tannins (0.22±0.04mg TAE/100g DM) compared to garlic (45±1.00mg GAE/100g DM, 34.66±0.57mg QE/100g DM, 6.8±0.34mg CE/100g DM and 0.05±0.01mg TAE/100g DM) respectively. Five compounds were found in red onion extract and one compound in garlic extract after chromatographic analysis of the samples. Furthermore, red onion possessed the higher antioxidant activity (IC50= 420.9±5.00 µg/ml) as compared to garlic (919.87±4.43 µg/ml). These findings provide ample evidence of the existence of bioactive compounds in garlic and red onion, both of which are rich in phenolics primarily flavonoids and tannins, have strong antioxidant activity, and can be further consumed directly or as food products.

Background Digital technologies have been widely acknowledged as a potentially useful resource for increasing mental healthcare access. The working alliance is a key influence on outcomes in conventional psychotherapy, but little is known about therapists’ experiences of forming an effective working alliance in blended interventions that involve in-person psychotherapy and a digital programme. Aims To investigate psychological well-being practitioners’ (PWPs’) experiences of the working alliance in a trial of blended cognitive–behavioural therapy (b-CBT) for depression. Trial registration ISRCTN12388725. Method Semi-structured qualitative interviews were conducted with 13 PWPs who delivered b-CBT in a two-arm, non-inferiority randomised controlled trial investigating the effectiveness of b-CBT compared with face-to-face CBT. Thematic analysis was used to analyse the data. Results Participants reported four facilitating factors when building and maintaining a working alliance in b-CBT: having more time to deliver treatment, access to a wider toolkit, capacity to tailor components of b-CBT and receiving appropriate training and support. Participants also identified four barriers to building and maintaining a working alliance: time and resource constraints, usability challenges, limited flexibility to tailor the digital programme to patients’ needs and lack of confidence in delivering b-CBT. Conclusions Our study is the first specifically to investigate practitioners’ perceived facilitators and barriers to forming a working alliance in b-CBT for depression. Findings suggest that PWPs’ experiences of the working alliance can be improved by: accounting for the time required to deliver b-CBT in service workflows to reduce time pressures; increasing opportunities to tailor the digital programme through offering transdiagnostic tools and adaptable features; and providing appropriate b-CBT training and technical support.

The objective of our study was to evaluate the wound healing effect of ethanolic extracts of pistachio (Pistacia lentiscus L.) leaves and holm oak (Quercus ilex L.) bark on full-thickness excisions (4 cm2) in Wistar rats. Forty-two rats were divided into seven equal groups that received different treatments; two groups were treated with Quercus ilex bark extract (10% and 30%), two other groups with Pistacia lentiscus leaves extract (10% and 30%), one group received Cicatryl-bio® and considered as a positive control, a group treated with pure Petroleum jelly, and the last was left as an untreated negative control. The evaluation of the excision zones was estimated by a planimetric study using an image processing software (ImageJ®) and histological examination of healed skin tissue. The results revealed that Pistacia lentiscus leaves and Quercus ilex bark promote wound healing effect because they accelerated wound contraction and reduced epithelialization period. Ointments prepared from Quercus ilex bark and Pistacia lentiscus leaves ethanolic extracts exhibited effective wound healing action in Wistar rat’s skin excisions. Both preparations showed an accelerated healing process compared to the other formulations. To the best of the author's knowledge, this is the first study of wound healing effect of pistachio (Pistacia lentiscus) leaves and holm oak (Quercus ilex) bark.

SummaryRecently, an intestinal dysbiotic microbiota with enrichment in oral cavity bacteria has been described in colorectal cancer (CRC) patients. Here we characterized and investigated one of these oral pathobionts, the Gram-positive anaerobic coccusParvimonas micra.We identified two phylotypes (A and B) exhibiting different phenotypes and adhesion capabilities. We observed a strong association of phylotype A with CRC, with its higher abundance in feces and in tumoral tissue compared with the normal homologous colonic mucosa, which was associated with a distinct methylation status of patients. By developing anin vitrohypoxic co-culture system of human primary colonic cells with anaerobic bacteria, we showed thatP. micraphylotype A alters the DNA methylation profile promoters of key tumor-suppressor genes, oncogenes, and genes involved in epithelial-mesenchymal transition. In colonic mucosa of CRC patients carryingP. micraphylotype A, we found similar DNA methylations alterations, together with significant enrichment of differentially expressed genes in pathways involved in inflammation, cell adhesion, and regulation of actin cytoskeleton, providing evidence ofP. micrapossible role in the carcinogenic process.

"Background: The use of digital mental health (MH) programs such as internet-based cognitive behavioural therapy (iCBT) hold promise in increasing the quality and access of MH services. However very little research has been conducted in understanding the feasibility of implementing iCBT in Eastern Europe. Methods: We used qualitative semi-structured focus group discussions (FGDs) that were guided by Bryan Weiner’s model of organisational readiness for implementing change. The questions broadly explored shared determination to implement change, (change commitment), and shared belief in their collective capability to do so (change efficacy). Data were collected between November and December 2017. A range of healthcare professionals working in and in association with the CMHCs were recruited from three CMHCs in Albania, and four CMHCs in Kosovo, which are participating in a large multinational trial on the implementation of iCBT across nine countries (Horizon 2020 ImpleMentAll project). Data were analysed using a directed approach to qualitative content analysis, which used a combination of both inductive and deductive approaches. Results: Six FGDs involving 69 MH care professionals were conducted. Participants from Kosovo (n=36, 52%) and Albania (n=33, 48%) were mostly female (n=48, 69.9%) and nurses (n=26, 37.7%), with an average age of 41.3 years. A qualitative directed content analysis revealed several barriers and facilitators potentially affecting the implementation of digital CBT interventions for depression in community MH settings. While commitment for change was high, change efficacy was limited due to a range of situational factors. Barriers impacting ‘change efficacy’ included lack of clinical fit for iCBT, high stigma affecting help-seeking behaviours, lack of human resources, poor technological infrastructure, and high caseload. Facilitators included having a high interest and capability in receiving training for iCBT. For ‘change commitment’, participants largely expressed welcoming innovation and that iCBT could increase access to treatments for geographically isolated people, and reduce the stigma associated with MH care. Conclusions: In all, participants perceived iCBT positively in relation to promoting innovation in MH care, increasing access to services and reducing stigma. On the other hand, a range of barriers were also highlighted in relation to accessing the target treatment population, a culture of MH stigma, underdeveloped ICT infrastructure and limited appropriately trained healthcare workforce, that reduce organisational readiness for implementing iCBT for depression. Such barriers may be addressed through, (a) a public facing campaign that addresses MH stigma, (b) service-level adjustments that permit staff with the time, resources and clinical supervision to deliver iCBT, and (c) establishment of suitable clinical training curriculum for healthcare professionals."

STUDY QUESTIONDo assisted reproductive technologies (ART) and in vitro embryo culture influence the epigenetic control of imprinted genes (IGs) and transposable elements (TEs) in children?SUMMARY ANSWERSignificant differences in the DNA methylation of IGs or transposon families were reported between ART and naturally conceived children, but there was no difference between culture media.WHAT IS KNOWN ALREADYThere is concern that ART may play a role in increasing the incidence of adverse health outcomes in children, probably through epigenetic mechanisms. It is crucial to assess epigenetic control, especially following non-optimal in vitro culture conditions and to compare epigenetic analyses from ART-conceived and naturally conceived children.STUDY DESIGN, SIZE, DURATIONThis follow-up study was based on an earlier randomized study comparing in vitro fertilization outcomes following the use of two distinct culture media. We compared the epigenetic profiles of children from the initial randomized study according to the mode of conception [i.e. ART singletons compared with those of a cohort of naturally conceived singleton children (CTL)], the type of embryo culture medium used [global medium (LifeGlobal) and single step medium (Irvine Scientific)] and the mode of in vitro fertilization (i.e. IVF versus ICSI).PARTICIPANTS/MATERIALS, SETTING, METHODSA total of 57 buccal smears were collected from 7- to 8-year-old children. The DNA methylation profiles of four differentially methylated regions (DMRs) of IGs (H19/IGF2: IG-DMR, KCNQ1OT1: TSS-DMR, SNURF: TSS-DMR, and PEG3: TSS-DMR) and two TEs (AluYa5 and LINE-1) were first assessed by pyrosequencing. We further explored IGs and TEs’ methylation changes through methylation array (Human MethylationEPIC BeadChip referred as EPIC array, Illumina).MAIN RESULTS AND THE ROLE OF CHANCEChanges in the IGs’ DNA methylation levels were found in ART children compared to controls. DNA methylation levels of H19/IGF2 DMR were significantly lower in ART children than in CTL children [52% versus 58%, P = 0.003, false discovery rate (FDR) P = 0.018] while a significantly higher methylation rate was observed for the PEG3 DMR (51% versus 48%, P = 0.007, FDR P = 0.021). However, no differences were found between the culture media. After observing these targeted modifications, analyses were performed at wider scale. Again, no differences were detected according to the culture media, but imprinted-related DMRs overlapping promoter region near the genes major for the development (MEG3, BLCAP, and DLX5) were detected between the ART and CTL children.LIMITATIONS, REASONS FOR CAUTIONThe sample size could seem relatively small, but the high consistency of our results was ensured by the homogeneity of the cohort from the initial randomized study, the standardized laboratory techniques and the robust statistical analyses accounting for multiple testing.WIDER IMPLICATIONS OF THE FINDINGSAlthough this study did not report DNA methylation differences depending on the culture medium, it sheds light on epigenetic changes that could be observed in some children conceived by ART as compared to CTL children. The clinical relevance of such differences remains largely unknown, and it is still unclear whether such changes are due to some specific ART procedures and/or to parental infertility.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by funding from the Agence Nationale pour la Recherche (‘CARE’-ANR JCJC 2017). The authors have no conflicts of interest.TRIAL REGISTRATION NUMBERNot concerned.

BACKGROUND Common mental health disorders (CMDs) are a leading cause of disability globally. The ongoing COVID-19 pandemic has further exacerbated the burden of CMDs. Despite the high burden of CMDs, a vast mental health care gap still exists in low-resourced settings. COVID-19 containment measures, including lockdowns, have further disrupted access to in-person mental healthcare. It is imperative to explore digital mental health interventions' utility to bridge the treatment gap. This study set to explore the utility of Inuka, a chat-based application hinged on the Friendship Bench problem-solving therapy intervention. OBJECTIVE To explore the feasibility of conducting a future clinical trial, including the feasibility, acceptability appropriateness, scalability, and preliminary effectiveness of Inuka. METHODS Concurrent mixed methods were used simultaneously to glean data on implementation and clinical parameters. We used a pragmatic non-equivalent control group quasi-experimental design to compare the feasibility, acceptability, and preliminary clinical effectiveness of Inuka (experimental group) compared to WhatsApp chat-based counselling (control intervention). Participants received six (6) problem-solving therapy sessions delivered by lay counsellors. A reduction in CMDs was the primary clinical outcome, and this was measured using the; Shona Symptoms Questionnaire, Patient Health Questionnaire (PHQ-9), and the generalised anxiety and depression scale (GAD-7). Health-related quality of life (HRQoL), disability and functioning, and social support were the secondary outcomes and were measured using the EQ-5D, WHO Disability Assessment Schedule and multidimensional scale of perceived social support, respectively. Quantitative outcomes were analysed using both descriptive and bivariate statistics. Last, we used administrative data and semi-structured interviews to gather data on acceptability and feasibility; this was analysed using descriptive statistics and thematic analysis. RESULTS Altogether, 258 participants were screened over six (6) months, with 202 assessed for eligibility. 176 participants were assigned to the study giving a recruitment ratio of 29 participants per month. The participants' mean age was 24.4 (SD 5.3) years, and most participants were females (65.8%), enrolled or completed tertiary education (55.3%) with a mean daily smartphone usage of 8 hours (SD 3.5). Eighty-three (83) users signed up and completed at least one session. The average completion rate was three sessions per participant. Inuka was deemed feasible and acceptable in the local context, with connectivity challenges, app instability, expensive mobile data and power outages cited as potential barriers to scale-up. Generally, there was a decline in CMDs (F (2,73) =2.63; P=0.079), depression (F (2,73) =7.67; p< .001), anxiety (F (2,73) =2.95; P=0.059 and a corresponding increase in HRQoL (F (2, 73) =7.287; P CONCLUSIONS Overall, study outcomes show it is feasible to run a future large-scale RCT and lend support to the feasibility and acceptability of Inuka, including evidence of preliminary effectiveness. CLINICALTRIAL N/A

Background Common mental health disorders (CMDs) are leading causes of disability globally. The ongoing COVID-19 pandemic has further exacerbated the burden of CMDs. COVID-19 containment measures, including lockdowns, have disrupted access to in-person mental health care. It is therefore imperative to explore the utility of digital mental health interventions to bridge the treatment gap. Mobile health technologies are effective tools for increasing access to treatment at a lower cost. This study explores the utility of Inuka, a chat-based app hinged on the Friendship Bench problem-solving therapy intervention. The Inuka app offers double anonymity, and clients can book or cancel a session at their convenience. Inuka services can be accessed either through a mobile app or the web. Objective We aimed to explore the feasibility of conducting a future clinical trial. Additionally, we evaluated the feasibility, acceptability, appropriateness, scalability, and preliminary effectiveness of Inuka. Methods Data were collected using concurrent mixed methods. We used a pragmatic quasiexperimental design to compare the feasibility, acceptability, and preliminary clinical effectiveness of Inuka (experimental group) and WhatsApp chat-based counseling (control). Participants received 6 problem-solving therapy sessions delivered by lay counselors. A reduction in CMDs was the primary clinical outcome. The secondary outcomes were health-related quality of life (HRQoL), disability and functioning, and social support. Quantitative outcomes were analyzed using descriptive and bivariate statistics. Finally, we used administrative data and semistructured interviews to gather data on acceptability and feasibility; this was analyzed using thematic analysis. Results Altogether, 258 participants were screened over 6 months, with 202 assessed for eligibility, and 176 participants were included in the study (recruitment ratio of 29 participants/month). The participants’ mean age was 24.4 (SD 5.3) years, and most participants were female and had tertiary education. The mean daily smartphone usage was 8 (SD 3.5) hours. Eighty-three users signed up and completed at least one session. The average completion rate was 3 out of 4 sessions. Inuka was deemed feasible and acceptable in the local context, with connectivity challenges, app instability, expensive mobile data, and power outages cited as potential barriers to scale up. Generally, there was a decline in CMDs (F2,73=2.63; P=.08), depression (F2,73=7.67; P Conclusions Study outcomes showed that it is feasible to run a future large-scale randomized clinical trial (RCT) and lend support to the feasibility and acceptability of Inuka, including evidence of preliminary effectiveness. The app’s double anonymity and structured support were the most salient features. There is a great need for iterative app updates before scaling up. Finally, a large-scale hybrid RCT with a longer follow-up to evaluate the clinical implementation and cost-effectiveness of the app is needed.

Background The distinction between grade 2 and 3 is instrumental to choose between observational follow-up and adjuvant treatment in resected astrocytoma IDH-mutant. However, criteria of grade 2 versus 3 have not been updated since the WHO 2007 classification. There is no consensus on the method of evaluation of the mitotic activity or a cut-off of mitoses separating grade 2 and grade 3 tumors. The objectives were to evaluate the maximal mitotic activity on a series of resected astrocytoma IDH-mutant and assess its prognostic impact on survival. Material and Methods Maximal mitotic activity on consecutive high power fields corresponding to 3 mm2 was examined in 118 lower-grade astrocytoma IDH-mutant. The prognostic value for time-to-treatment (TTT) and overall survival (OS) of mitotic activity and other putative prognostic factors (including age, performance status, pre-surgical tumor volume, plurilobar involvement, post-surgical residual tumor volume, midline involvement) was assessed in tumors with (i) ATRX loss, and (ii) without CDKN2A homozygous deletion, lesional enhancement, histological necrosis nor microvascular proliferation. Results Among the 75 (64%) of tumors which had gone through observational follow-up after resection, the maximal mitotic activity, the post-surgical residual volume and the plurilobar involvement were independent prognostic factors of TTT (p < 0.0001). A threshold of mitotic activity for grade 2 was fitted on TTT and OS prognosis. Using this threshold, patients with “grade 2 tumors” had a median TTT of 55 months versus 19 months for “grade 3” (p = 0.0057) and a median OS of 102 months versus 73 months respectively (p = 0.001). Residual volume < 1 cm3 was associated with longer OS (113 months versus 88 months, p = 0.0021). Conclusion Mitotic activity and post-surgical residual volume can be combined to evaluate prognosis in resected astrocytoma IDH-mutant and could select the best candidates for observational follow-up.

Background: The microbial evolution of the J’ben Elgafs prepared with raw milk from local cows, was studied during the manufacturing and maturating process in order to characterize this variety of cheese from the Algerian terroir.Methods: The microbial activity and physical-chemical parameters were tested during the three dairy seasons of the year. Total, lactics and alteration floras were counted on their selective environments.Result: Lactic germs multiply considerably during the first days and only stabilize towards the end of maturation. The low presence of alteration floras is the result of the continuous modification of the physico-chemical parameters of Aw and pH from one stage to the other of the j’ben production and the respect of good processing practices. These different proportions of variation are induced by the biochemical reactions and microbial interactions that take place responsible for the sequential growth of one microbial group compared to another.

BACKGROUND The use of digital mental health programs such as internet-based cognitive behavioral therapy (iCBT) holds promise in increasing the quality and access of mental health services. However very little research has been conducted in understanding the feasibility of implementing iCBT in Eastern Europe. OBJECTIVE The aim of this study was to qualitatively assess organizational readiness for implementing iCBT for depression within community mental health centers (CMHCs) across Albania and Kosovo. METHODS We used qualitative semistructured focus group discussions that were guided by Bryan Weiner’s model of organizational readiness for implementing change. The questions broadly explored shared determination to implement change (change commitment) and shared belief in their collective capability to do so (change efficacy). Data were collected between November and December 2017. A range of health care professionals working in and in association with CMHCs were recruited from 3 CMHCs in Albania and 4 CMHCs in Kosovo, which were participating in a large multinational trial on the implementation of iCBT across 9 countries (Horizon 2020 ImpleMentAll project). Data were analyzed using a directed approach to qualitative content analysis, which used a combination of both inductive and deductive approaches. RESULTS Six focus group discussions involving 69 mental health care professionals were conducted. Participants from Kosovo (36/69, 52%) and Albania (33/69, 48%) were mostly females (48/69, 70%) and nurses (26/69, 38%), with an average age of 41.3 years. A directed qualitative content analysis revealed several barriers and facilitators potentially affecting the implementation of digital CBT interventions for depression in community mental health settings. While commitment for change was high, change efficacy was limited owing to a range of situational factors. Barriers impacting “change efficacy” included lack of clinical fit for iCBT, high stigma affecting help-seeking behaviors, lack of human resources, poor technological infrastructure, and high caseload. Facilitators included having a high interest and capability in receiving training for iCBT. For “change commitment,” participants largely expressed welcoming innovation and that iCBT could increase access to treatments for geographically isolated people and reduce the stigma associated with mental health care. CONCLUSIONS In summary, participants perceived iCBT positively in relation to promoting innovation in mental health care, increasing access to services, and reducing stigma. However, a range of barriers was also highlighted in relation to accessing the target treatment population, a culture of mental health stigma, underdeveloped information and communications technology infrastructure, and limited appropriately trained health care workforce, which reduce organizational readiness for implementing iCBT for depression. Such barriers may be addressed through (1) a public-facing campaign that addresses mental health stigma, (2) service-level adjustments that permit staff with the time, resources, and clinical supervision to deliver iCBT, and (3) establishment of a suitable clinical training curriculum for health care professionals. CLINICALTRIAL ClinicalTrials.gov NCT03652883; https://clinicaltrials.gov/ct2/show/NCT03652883

Alzheimer’s disease (AD) is a common disease of the older population around the world. It causes a progressive neurodegenerative disorder linked to age. The undesirable effects of treatments for this disease limit the use of conventional drugs. However, currently scientists are interested in researching more effective natural medicines. Various plants and herbal preparations have been traditionally used for their memory and cognition enhancing abilities; many of which were extensively studied for therapeutic potential in Alzheimer’s disease. Melissa officinalis (lemon balm) is a medicinal plant that has a long history of use in the treatment of diseases, especially nervous system disorders. This review is aimed to present this plant (taxonomy, cultivation, phytochemical profile, traditional usages and pharmacology, treatment, mechanism of action, and safety) and also to summarize its neuroprotective, antioxidant, and anti-inflammatory characteristics in Alzheimer’s disease.

Additional file 4. “Results of CASP Assessment”.

Hypericum perforatum L. (Hypericaceae) is a perennial plant commonly known as St. John’s Wort that has been used for centuries as a medicinal herb (it has antidepressant, antiviral, wound healing, antiinflammatory, etc. properties). It contains numerous pharmacologically active ingredients, including naphthodianthrones (hypericin, pseudohypericin). These natural compounds have beneficial activity in neurodegenerative disorders, such as Alzheimer’s disease, because of their neuroprotective and antidepressant properties.

Additional file 3. “Results of EPHPP Assessment”.

Additional file 5. “Search Terms for Ovid MEDLINE(R)”.

Homeless people experience a unique set of challenges leading to pervasive health and social problems. An increasing number of researchers have harnessed photographic data to gain a unique perspective of marginalised groups. The aim of the study is to explore the feasibility of using photographs in research to understand the complex environment experienced by homeless people, with a special interest in mental health. Individuals who frequently attend homeless facilities in London were sensitively approached and asked if they would be interested in taking part in the ‘Views From the Street’ pilot study. Once agreement was confirmed through a formal consenting procedure, participants were asked to visually capture and upload their own digital photos, along with a brief description. The collection of data highlighted a number of barriers to engagement and acceptability, including issues around the level of familiarity with the recruiter, practicalities of participation, public perception of phone use, poor technical literacy, anonymity, and disassociation with the ‘homeless’ label. Recommendations are made for future research utilising photographic participatory designs with the homeless population.

Resume Objectifs. La nandrolone est un anabolisant norsteroide de synthese aux proprietes androgeniques connues. A l'aube de la Coupe du Monde 1998, la polemique concernant la possibilite d'une synthese endogene de nandrolone a des taux superieurs a ceux pris en compte par le Comite international olympique (CIO), n'a ete entretenue que par l'expression publique du manque de rigueur de certains ≪ scientifiques ≫. Nous montrerons ici pourquoi elle a fait ≪ long feu ≫. Origine des norsteroides, le point de la recherche. Ces substances sont des intermediaires biochimiques obligatoires dans l'aromatisation des androgenes. Dans les annees 1990, la chromatographie gazeuse couplee a la spectrometrie de masse a permis d'abaisser le seuil de detection de ces substances a 1 pg/mL voire moins ce qui rend possible la quantification de taux infimes de metabolites endogenes qui n'ont rien a voir avec les taux eleves rapportes lors des controles antidopage de 1997–1998. Nous ferons le point sur la biologie de la nandrolone et des norsteroides. Perspectives et conclusions. Face au grave probleme de sante publique que represente la prise abusive d'anabolisants a doses pharmacologiques, la rigueur scientifique des controles, dans le cadre du suivi medical des sportifs, est justifiee et confortee.

Le dopage par les androgenes est l’utilisation de substances derivees ou apparentees a la testosterone a des fins d’amelioration de la performance sportive. Toute prise d’androgene est illegale de par la Loi du 28 Juin 89 relative au sport. Il n’existe pas, pour cette classe de substances, de justification therapeutique possible. Le Comite Medical d’Ethique a confirme cette decision legale en 1993. Les moyens utilises actuellement pour mettre en evidence cette utilisation illegale sont revus ici. En bref, le depistage de l’utilisation illegale d’an-drogenes commence par la recherche des differents anabolisants de synthese dans un echantillon d’urine d’un competiteur. La seule technique utilisee et reconnue officiellement dans le cadre du depistage du dopage est la chromatographie gazeuse couplee a la spectrometrie de masse (GC/MS).

Estradiol and progesterone receptors (ER and PR) were studied in 46 breast fibroadenomas obtained at different periods of the menstrual cycle (n = 38) or from patients under combined estrogen-progestagen contraceptive (n = 4) or substitutive progestagen treatment for progesterone insufficiency (n = 4). Cytosolic and nuclear ER (ERc and ERn) increased throughout the follicular phase and were at their maximal level in the preovulatory phase. They decreased during the luteal phase. PR levels were high in the follicular phase, especially in the cytosol (PRc). PRc then decreased while nuclear progesterone receptor (PRn) increased at the beginning of the luteal phase. Thereafter, PRc and PRn decreased and remained low during the luteal phase. PRc and PRn levels in fibroadenomas from patients under estrogen-progestagen therapy were similar to those found during the luteal phase of untreated patients. In patients receiving a substitutive progestagen treatment to correct progesterone insufficiency, PRn was markedly higher than PRc. The existence of ER and PR in breast fibroadenomas and the variations in their levels during the menstrual cycle or under hormonal treatment provide valuable information on the hormone dependency of breast fibroadenoma.

We have measured the total (cytosolic plus nuclear) androgen binding capacity of pubic skin fibroblasts from nine patients with hirsutism of various origin. Confluent intact cell monolayers were incubated with increasing concentrations (0.05-2 nM) of [3H]dihydrotestosterone ([3H]DHT) with or without a 200-fold excess of unlabeled DHT. The androgen binding capacities (mean +/- SD) were similar in normal men (411 +/- 171 fmol/mg DNA), women (310 +/- 103 fmol/mg DNA), and hirsute patients (313 +/- 141 fmol/mg DNA) regardless of the plasma androgen levels. In contrast, the 5 alpha-reductase level in pubic skin fibroblasts (mean +/- SD) was, as previously described, higher in hirsute women (3.3 +/- 2.6 fmol/micrograms DNA . h) than in normal women (1.1 +/- 0.6 fmol/microgram DNA . h; P less than 0.05). We conclude from these data that: 1) increased androgen binding capacity cannot be held responsible for hypersensitivity to androgens in hirsutism; 2) the androgen receptor is not regulated by androgens in human skin, as similar levels are observed in men, women, and hirsute patients; 3) this contrasts with 5 alpha-reductase activity and emphasizes the importance of this enzyme as an amplifier of androgen action in areas where it is stimulated by androgens, such as pubic skin.

The nuclear matrix (NM) is a salt and nuclease-resistant nuclear substructure. It is associated with active DNA transcription and has been shown to contain acceptor sites for steroid receptors in a number of specific target tissues. We have investigated the presence of acceptor sites for the androgen receptor (AR) in the NM of human newborn foreskin. The NM was prepared from the 800 g pellet by successive treatments with detergent, DNase and high salt extraction. It contained 13 +/- 7% of total proteins and 10 +/- 6% of total DNA. After extensive washing, the NM spheres were incubated in the presence of cytosol and [3H]methyltrienolone +/- 200-fold excess of unlabeled steroid. Maximal binding of the AR to NM was reached in 30 min and decreased slightly thereafter to reach an equilibrium which was maintained for 18 h. Binding was saturable. In the absence of AR, the steroid did not bind to NM. When Scatchard analysis was performed on cytosol previously incubated with NM, cytosolic binding capacity significantly decreased relative to preincubation values (3.6 +/- 1.9 to 1.3 +/- 1.2 fmol/mg protein, P less than 0.05, n = 6). In contrast, apparent binding affinity was not changed. 0.8 mg of NM protein could bind AR from 2.4 mg of cytosol protein. In conclusion, NM from human foreskin binds the AR with high affinity. This binding is rapid and is maintained for at least 18 h. This is consistent with a potential role of NM in the mechanism of action of androgens in their target tissues.