DeepD3, an open framework for automated quantification of dendritic spines.

Dendritic spines are the seat of most excitatory synapses in the brain, and a cellular structure considered central to learning, memory, and activity-dependent plasticity. The quantification of dendritic spines from light microscopy data is usually performed by humans in a painstaking and error-prone process. We found that human-to-human variability is substantial (inter-rater reliability 82.2±6.4%), raising concerns about the reproducibility of experiments and the validity of using human-annotated 'ground truth' as an evaluation method for computational approaches of spine identification. To address this, we present DeepD3, an open deep learning-based framework to robustly quantify dendritic spines in microscopy data in a fully automated fashion. DeepD3's neural networks have been trained on data from different sources and experimental conditions, annotated and segmented by multiple experts and they offer precise quantification of dendrites and dendritic spines. Importantly, these networks were validated in a number of datasets on varying acquisition modalities, species, anatomical locations and fluorescent indicators. The entire DeepD3 open framework, including the fully segmented training data, a benchmark that multiple experts have annotated, and the DeepD3 model zoo is fully available, addressing the lack of openly available datasets of dendritic spines while offering a ready-to-use, flexible, transparent, and reproducible spine quantification method.

Evaluation of the effectiveness of three sticky traps to monitor four species of cockroaches (Hexapoda: Blattaria) with simulated use tests.

Background: Cockroaches are the pest of major concern for the disinfestation programs of the sanitary system in Italy. Hygienic-sanitary interest is linked to the role of mechanical vectors of pathogens and to their allergological potential. Sticky traps are the best tool to monitor the presence of these insects and several types of them are available on the market. In most of the cases the traps are not indicated for a given species, but, instead, generically for cockroaches. Domestic cockroaches differ in morphology, size and habits. Consequently, the effectiveness of the trap can change in relation to the target species. Materials and methods: In this study three of the most employed traps in Italy were compared: the INDIA trap with and without its attractant tablet (hereafter mentioned as INDIA-A and INDIA-E, respectively), the ZAPI Simply trap and the CATCHMASTER Spider & Insect Glue trap. We chose the four most common species of cockroach (Blattodea) in Italy, Blatta orientalis (L.), Periplaneta americana (L.) (Blattidae), Blattella germanica (L.) and Supella longipalpa (F.) (Blattellidae). Each species of cockroach was tested separately inside arenas containing one of the traps. Each test (one species with one kind of trap) was replicated five times. Results and discussion: The INDIA-A trap collected more cockroaches of every species, followed by the INDIA-E. The ZAPI trap caught less specimens of each species in respect to the INDIA traps, with the only exception of B. orientalis, for which the ZAPI trap caught more than the INDIA-E. The CATCHMASTER trap performed significantly less for all the species. B. orientalis was the species most abundantly caught by all traps, followed by B. germanica, S. longipalpa and P. americana. No significant difference was observed in the catch according to the developmental stage. In general, there was no particular predisposition of any trap to catch a particular species. Conclusions: It is not possible to indicate a model of trap for each species of cockroach, but it is clear that different traps have different performances in terms of attractiveness and capture. Therefore, the choice of the trap affects the results of the monitoring, and as consequence, the evaluation of the infesting population of the pest.

Prevention of chemotherapy-induced nausea and vomiting in the real-world setting in Spain

Purpose Proper monitoring and management of chemotherapy-induced nausea and vomiting (CINV) with antiemetics is crucial for cancer patients. This study aimed to evaluate the use of antiemetics for the treatment of highly emetogenic chemotherapy (HEC) including carboplatin in the real-world setting in Spain. Methods A representative panel of cancer specialists was asked to collect information about the antiemetic treatments provided to patients receiving chemotherapy. Records formed part of the Global Oncology Monitor© database (Ipsos Healthcare, London, UK). Chemotherapy data were extrapolated using Ipsos Healthcare’s projection methodology. Results A total of 73 experts were finally included. Data from 9519 patients, estimated to be representative of 202,084 patients, were collected. HEC (and carboplatin-based chemotherapy) was administered to 73,118 (36%) patients, cisplatin-based therapy being the most frequent treatment (n = 34,649, 47.38%). Neurokinin-1 receptor antagonists (NK1RAs) alone or in combination were used as prophylaxis for CINV in 14,762 (20%) patients, while the combination of NK1RA with 5-hydroxytryptamine-3 receptor antagonist (5-HT3RAs) and dexamethasone as recommended by the international guidelines was used in 5849 (8%) patients only. No antiemetic prophylaxis was administered to 8.46% of the patients receiving HEC (n = 6189). Physicians classified cisplatin-, anthracycline-cyclophosphamide (AC-), and carboplatin-based regimens as HEC in 63%, 22% and 4% of the cases, respectively. Conclusions The use of NK1RA-containing regimens for CINV prevention in patients treated with HEC was less than expected, suggesting poor adherence to international antiemetic guidelines (AU)

Prevention of chemotherapy-induced nausea and vomiting in the real-world setting in Spain.

PURPOSE: Proper monitoring and management of chemotherapy-induced nausea and vomiting (CINV) with antiemetics is crucial for cancer patients. This study aimed to evaluate the use of antiemetics for the treatment of highly emetogenic chemotherapy (HEC) including carboplatin in the real-world setting in Spain. METHODS: A representative panel of cancer specialists was asked to collect information about the antiemetic treatments provided to patients receiving chemotherapy. Records formed part of the Global Oncology Monitor© database (Ipsos Healthcare, London, UK). Chemotherapy data were extrapolated using Ipsos Healthcare's projection methodology. RESULTS: A total of 73 experts were finally included. Data from 9519 patients, estimated to be representative of 202,084 patients, were collected. HEC (and carboplatin-based chemotherapy) was administered to 73,118 (36%) patients, cisplatin-based therapy being the most frequent treatment (n = 34,649, 47.38%). Neurokinin-1 receptor antagonists (NK1RAs) alone or in combination were used as prophylaxis for CINV in 14,762 (20%) patients, while the combination of NK1RA with 5-hydroxytryptamine-3 receptor antagonist (5-HT3RAs) and dexamethasone as recommended by the international guidelines was used in 5849 (8%) patients only. No antiemetic prophylaxis was administered to 8.46% of the patients receiving HEC (n = 6189). Physicians classified cisplatin-, anthracycline-cyclophosphamide (AC-), and carboplatin-based regimens as HEC in 63%, 22% and 4% of the cases, respectively. CONCLUSIONS: The use of NK1RA-containing regimens for CINV prevention in patients treated with HEC was less than expected, suggesting poor adherence to international antiemetic guidelines.

Was GW190814 a Black Hole-Strange Quark Star System?

We investigate the possibility that the low mass companion of the black hole in the source of GW190814 was a strange quark star. This possibility is viable within the so-called two-families scenario in which neutron stars and strange quark stars coexist. Strange quark stars can reach the mass range indicated by GW190814, M∼(2.5-2.67) M_{⊙} due to a large value of the adiabatic index, without the need for a velocity of sound close to the causal limit. Neutron stars (actually hyperonic stars in the two-families scenario) can instead fulfill the presently available astrophysical and nuclear physics constraints which require a softer equation of state. In this scheme it is possible to satisfy both the request of very large stellar masses and of small radii while using totally realistic and physically motivated equations of state. Moreover it is possible to get a radius for a 1.4 M_{⊙} star of the order or less than 11 km, which is impossible if only one family of compact stars exists.

Insects and SARS-CoV-2: Analysis of the Potential Role of Vectors in European Countries.

ABSTRACT: SARS-CoV-2 is a coronavirus responsible for the pandemic that developed in China in late 2019. Transmission of the virus is predominantly direct, through exposure to infected respiratory secretions. As far as we know, arthropods play a key role in the transmission and spread of several viruses, and thus their role in the spread of COVID-19 deserves to be studied. The biological transmission of viral agents through insects is very complex. While mechanical transmission is more likely to happen, biological transmission is possible via blood-sucking arthropods, but this requires a high grade of compatibility between the vector and the pathogen. If the biological and mechanical transmission of SARS-CoV-2 by blood-sucking arthropods is excluded, a mechanical transmission by urban pests could take place. This risk is very low but it could be important in isolated environmental conditions, where other means of transmission are not possible. The presence of SARS-CoV-2 in non-blood-sucking arthropods in infected buildings, like hospitals and retirement homes, should be investigated.

Distributed chromatic processing at the interface between retina and brain in the larval zebrafish.

Larval zebrafish (Danio rerio) are an ideal organism for studying color vision, as their retina possesses four types of cone photoreceptors, covering most of the visible range and into the UV.1,2 Additionally, their eye and nervous systems are accessible to imaging, given that they are naturally transparent.3-5 Recent studies have found that, through a set of wavelength-range-specific horizontal, bipolar, and retinal ganglion cells (RGCs),6-9 the eye relays tetrachromatic information to several retinorecipient areas (RAs).10-13 The main RA is the optic tectum, receiving 97% of the RGC axons via the neuropil mass termed arborization field 10 (AF10).14,15 Here, we aim to understand the processing of chromatic signals at the interface between RGCs and their major brain targets. We used 2-photon calcium imaging to separately measure the responses of RGCs and neurons in the brain to four different chromatic stimuli in awake animals. We find that chromatic information is widespread throughout the brain, with a large variety of responses among RGCs, and an even greater diversity in their targets. Specific combinations of response types are enriched in specific nuclei, but there is no single color processing structure. In the main interface in this pathway, the connection between AF10 and tectum, we observe key elements of neural processing, such as enhanced signal decorrelation and improved chromatic decoding.16,17 A richer stimulus set revealed that these enhancements occur in the context of a more distributed code in tectum, facilitating chromatic signal association in this small vertebrate brain.

[Dysthyroidism in children and adolescents at the Mali hospital]. / Dysthyroïdie chez les enfants et les adolescents à l'hôpital du Mali.

INTRODUCTION: Dysthyroidism (hyperthyroidism or hypothyroidism) in children and adolescents is much rarer than in adults. The purpose of our study was to study the epidemiological, clinical, paraclinical, etiological and etiological aspects and to specify the therapeutic and evolutionary modalities of this condition. METHOD: This was a five-year descriptive, retrospective and prospective study of children and adolescents under 18 years of age with dysthyroidism. RESULTS: We collected 90 children and adolescents with dysthyroidism (hyperthyroidism 77.8% (n=70) and hypothyroidism 22.2% (n=20). For hyperthyroidism (n=70): the average age was 13.07 years and the sex ratio was 0.16. The family history of dysthyroidism was found in 24.3% (n=17). Clinical manifestations were dominated by tachycardia 88.57% (n=62), weight loss 87.14% (n=61), vibrating pulse 87.14% (n=61) and palpitation 81.42% (n=57). Bilateral exophthalmos was present in 70% of patients (n=49) with palpebral retraction in 51.42% (n=56). Goitre was present in 54 patients (77.1%). It was diffuse in 62.9% (n=44) and nodular in 12.9% (n=9). Basedow's disease represented the first etiology with 84.3% (n=59), followed by toxic multinodular goitre12, 9% (n=9). Sixty-eight patients (97.1%) received medical treatment with synthetic antithyroid drugs. Clinical remission was achieved in 64.3% (n=45) and 54.3% of patients were in biological euthyroidism at 6 months follow-up. For hypothyroidism (n=20): the average age was 10.70 years and the sex ratio was 0.53. Six family cases of hypothyroidism and three cases of family goitre were found. The clinical picture was dominated by signs of hypo metabolism at hypersomnia type 95% (n=19) and anorexia 75% (n=15). The skin was dry in 60% (n=12). A staturo-weight delay in 65% (n=13), behavioural disorders in 55% (n=11), weight gain in 40% (n=8) and puberty delay in 10% (n=2). Goitre was nodular in 25% (n=5) with cervical adenopathy present in 15% (n=3). Hashimoto's thyroiditis accounted for 45% (n=9) of etiologies followed by iodine deficiency disorders in 15% (n=3) and iatrogenic causes (2 cases of thyroidectomy). All patients were started on hormone replacement therapy for life. Five patients with large multinodular goiter received total thyroidectomy in addition to medical treatment. Euthyroidism was observed in 55% (n=11) of patients at 6 months follow-up. CONCLUSION: Dysthyroidism in children and adolescents exists in our health facilities. Its management is deficient because of the technical and financial platform. Our public health decision-makers must help implement a screening strategy to facilitate faster diagnosis and treatment.

INTRODUCTION: La dysthyroïdie (hyperthyroïdie ou hypothyroïdie) chez l'enfant et l'adolescent est beaucoup plus rare que chez l'adulte. Notre étude avait pour but d'étudier les aspects épidémiologiques, cliniques, paracliniques, étiologiques et de préciser les modalités thérapeutiques et évolutives de cette affection. MÉTHODE: Il s'agissait d'une étude descriptive, rétrospective et prospective de cinq ans portant sur les enfants et adolescents âgés de moins de 18 ans présentant une dysthyroïdie. RÉSULTATS: Nous avons colligé 90 enfants et adolescents présentant une dysthyroïdie (hyperthyroïdie 77,8% (n=70) et hypothyroïdie 22,2% (n=20).Pour l'hyperthyroïdie (n=70) : l'âge moyen était de 13,07 ans et le sex ratio de 0,16. L'antécédent familial de dysthyroïdie était retrouvé dans 24,3% (n=17). Les manifestations cliniques étaient dominées par la tachycardie 88,57% (n=62), l'amaigrissement 87,14% (n=61), le pouls vibrant 87,14% (n=61) et la palpitation 81,42% (n=57).L'exophtalmie bilatérale était présente chez 70% des patients (n=49) avec rétraction palpébrale dans 51,42% (n=56). Le goitre était présent chez 54 patients (77,1%). Il était diffus dans 62,9% (n=44) et nodulaire dans 12,9% (n=9). La maladie de Basedow représentait la première étiologie avec 84,3% (n=59), suivie du goitre multinodulaire toxique12, 9% (n=9). Soixante-huit patients (97,1%) ont bénéficié d'un traitement médical par antithyroïdien de synthèse. La rémission clinique était obtenue chez 64,3% (n=45) et 54,3% des patients étaient en euthyroïdie biologique au bout 6 mois de suivi. Pour l'hypothyroïdie (n=20) : l'âge moyen était de 10,70 ans et le sex ratio à 0,53. Six cas familiaux d'hypothyroïdie et trois cas de goitre familial étaient retrouvés. Le tableau clinique était dominé par les signes d'hypo métabolisme à type d'hypersomnie 95% (n=19) et d'anorexie 75% (n=15). La peau était sèche dans 60% (n=12). Un retard staturo-pondéral dans 65% (n=13), les troubles du comportement dans 55% (n=11), la prise pondérale chez 40% (n=8) et le retard pubertaire chez 10% (n=2). Le goitre était nodulaire chez 25% (n=5) avec présence d'adénopathies cervicales dans 15% (n=3). La thyroïdite d'Hashimoto représentait 45% (n=9) des étiologies suivies des troubles dus à la carence iodée dans 15% (n=3) et des causes iatrogéniques (2 cas de thyroïdectomie). Tous les patients ont été mis sous traitement hormonal substitutif à vie. Cinq patients ayant un volumineux goitre multinodulaire ont bénéficié en plus du traitement médical une thyroïdectomie totale. L'euthyroïdie était observée chez 55% (n=11) des patients au bout 6 mois de suivi. CONCLUSION: La dysthyroïdie chez les enfants et les adolescents existe dans nos structures de santé. Sa prise en charge est déficiente à cause du plateau technique et financier. Nos décideurs en santé publique doivent aider à la mise en place d'une stratégie de dépistage pour faciliter le diagnostic et le traitement plus rapide.

Amyand's hernia: role of CT for a correct diagnosis.

Amyand's hernia consists in the protrusion of the vermiform appendix into an inguinal hernia sac and represents an uncommon condition with a difficult preoperative diagnosis to be recognized with clinical examination and imaging diagnostic tools in order to choose a correct therapeutic approach for the patient. Four types of Amyand's hernias exist. The case of a recurrent type 1 Amyand's hernia is presented. Multi detector computed tomography allowed a correct diagnosis and the subsequent surgical treatment had no complication for the patient. Radiologists and surgeons need to be aware of this pathology and its classification, as well as of the importance of recognizing both the inflamed and normal appendix within the inguinal canal and the abdominal complications. With the availability of multi detector CT scanning, a greater number of type 1 and 2 hernias are able to be preoperatively diagnosed, and type 3 and 4 better characterized in emergency situation, allowing to perform the best surgical treatment and reducing the chances of pathological recurrence.

[Epidemiological And Clinical Survey Of The Diabetes Sweetens In A Center Of Health Of Reference Of Sikasso]. / Etude Epidemiologique Et Clinique Du Diabete Sucre Dans Un Centre De Sante De Reference De Sikasso.

GOAL: To study the diabetes sweetened in farming environment in the sanitary district of Selingue (CS Ref of Selingue). MATERIALS AND METHODS: It was about a descriptive survey done from January 01 to June 30, 2016 with a prospective compilation of data in the center of health of reference of Selingue (CS Ref of Selingue). All our patients benefitted from a complete clinical exam with research of factor of risk and reverberation of the diabetes.The statistical test used was Chi-square 2 with a threshold of significance p ≤ 0.05. RESULTS: Among the 1 525 patients collected, 84 were diabetic is a hospitable frequency of 5, 51% and the average age of 51, 43 years ±12, 25.The sex ratio was 1, 33. Diabetes type 2 was in 98% of cases. We did not record specific diabetes or gestational diabetes. A sedentary lifestyle was found in 70, 23% of the cases followed by Dyslipidemia with 42.85% of the cases. 1.2% of our patients presented an AOMI, a fifth of our patients have suffered from erectile dysfunction, 2/3 had a diabetic neuropathy and 4% had a wound. (P: 0.048) neuropathy and nephropathy (p: 0.016) diabetic were correlated with blood sugar imbalance. CONCLUSION: the gravity, the inaccessibility and the cost raised of the follow-up balances in Selingue limit the hold in charge of the diabetes in this sanitary district.

BUT: Etudier le diabète sucré en milieu rural dans le district sanitaire de Sélingué (CS Réf Sélingué). MATÉRIELS ET MÉTHODES: Il s'agissait d'une étude descriptive effectuée du 01 janvier au 30 juin 2016 avec un recueil prospectif des données au Centre de Santé de Référence de Sélingué (CS Réf de Sélingué). Tous nos patients ont bénéficié d'un examen clinique complet avec recherche de facteurs de risque et de retentissement du diabète. Le test statistique utilisé était le Khi 2 avec un seuil de significativité p ≤ 0,05. RÉSULTATS: Parmi les 1 525 dossiers de patients colligés, 84 était diabétiques soit une fréquence hospitalière de 5,51 % et l'âge moyen de 51,43 ans ± 12,25. Le sex ratio était de 1, 33. Le diabète était de type 2 dans 98% des cas. La sédentarité était retrouvée dans 70,23 % des cas suivie de la dyslipidémie avec 42,85 % des cas. 1,2 % de nos patients ont présenté une AOMI, un cinquième de nos patients ont souffert d'une dysfonction érectile, 2/3 avaient une neuropathie diabétique et 4 % avait une plaie. La neuropathie (p: 0,048) et la néphropathie (p: 0,016) diabétique étaient corrélées au déséquilibre glycémique. CONCLUSION: La gravité, l'inaccessibilité et le coût élevé des bilans de suivi à Sélingué limitent la prise en charge du diabète dans ce district sanitaire.

Etude épidémiologique et clinique du diabète sucré dans un centre de santé de référence de Sikasso

But: Etudier le diabète sucré en milieu rural dans le district sanitaire de Sélingué (CS Réf Sélingué).Matériels et méthodes : Il s'agissait d'une étude descriptive effectuée du 01 janvier au 30 juin 2016 avec un recueil prospectif des données au Centre de Santé de Référence de Sélingué (CS Réf de Sélingué). Tous nos patients ont bénéficié d'un examen clinique complet avec recherche de facteurs de risque et de retentissement du diabète. Le test statistique utilisé était le Khi 2 avec un seuil de significativité p ≤ 0,05. Résultats : Parmi les 1 525 dossiers de patients colligés, 84 était diabétiques soit une fréquence hospitalière de 5,51 % et l'âge moyen de 51,43 ans ± 12,25. Le sex ratio était de 1, 33. Le diabète était de type 2 dans 98% des cas. La sédentarité était retrouvée dans 70,23 % des cas suivie de la dyslipidémie avec 42,85 % des cas. 1,2 % de nos patients ont présenté une AOMI, un cinquième de nos patients ont souffert d'une dysfonction érectile, 2/3 avaient une neuropathie diabétique et 4 % avait une plaie. La neuropathie (p: 0,048) et la néphropathie (p: 0,016) diabétique étaient corrélées au déséquilibre glycémique. Conclusion : La gravité, l'inaccessibilité et le coût élevé des bilans de suivi à Sélingué limitent la prise en charge du diabète dans ce district sanitaire

The containment of potential outbreaks triggered by imported Chikungunya cases in Italy: a cost utility epidemiological assessment of vector control measures.

The arrival of infected travelers from endemic regions can trigger sustained autochthonous transmission of mosquito-borne pathogens in Europe. In 2007 a Chikungunya outbreak was observed in central Italy, mostly affecting two villages characterised by a high density of Aedes albopictus. The outbreak was mitigated through intervention strategies reducing the mosquito abundance. Ten years later, in 2017, sustained Chikungunya transmission was documented in both central and southern Italy. The proposed analysis identifies suitable reactive measures for the containment and mitigation of future epidemics by combining epidemiological modeling with a health economic approach, considering different arrival times of imported infections and possible delays in the notification of cases. Obtained estimates suggest that, if the first notification will occur in the middle of the mosquito breeding season, the combination of larvicides, adulticides and breeding sites removal represents the optimal strategy. In particular, we found that interventions implemented in 2007 were cost-effective, with about 3200 prevented cases, 1450 DALYs averted and €13.5 M saved. Moreover, larvicides are proven to be more cost beneficial in early summer and warmer seasons, while adulticides should be preferred in autumn and colder seasons. Our results provide useful indications supporting urgent decision-making of public health authorities in response to emerging mosquito-borne epidemics.

Toxicity risk assessment of mercury, DDT and arsenic legacy pollution in sediments: A triad approach under low concentration conditions.

The determination of sediment toxicity is challenging due to site-specific factors affecting pollutants distribution and bioavailability, especially when contamination levels are close to expected non-effect concentrations. Different lines of evidence and sensitive tools are necessary for a proper toxicity risk assessment. We examined the case study of the Toce River (Northern Italy), where past industrial activities determined Hg, DDT and As enrichment in sediments. A triad approach comprising chemical, ecotoxicological and ecological analyses (benthic invertebrates) was carried out for risk assessment of residual contamination in river sediments. A "blank" site upstream from the industrial site was selected to compare the other sites downstream. Sediment, water and benthic invertebrate samplings were carried out following standard protocols. Results emphasized that despite the emissions of the industrial site ceased about 20years ago, sediments in the downstream section of the river remain contaminated by Hg, DDT and As with concentrations exceeding Threshold Effect Concentrations. A chronic whole-sediment test with Chironomus riparius showed decreased development rate and a lower number of eggs per mass in the contaminated sediments. Benthic community was analyzed with the calculation of integrated (STAR_ICMi) and stressor-specific metrics (SPEARpesticide and mean sensitivity to Hg), but no significant differences were found between upstream and downstream sites. On the other hand, multivariate analysis (partial Redundancy Analysis and variation partitioning) emphasized a slight impact on invertebrate community, accounting for 5% variation in taxa composition. Results show that legacy contaminants in sediments, even at low concentrations, may be bioavailable and possibly toxic for benthic invertebrates. At low concentration levels, sensitive and site-specific tools need to be developed for a proper risk analysis.

Properties of the Visible Light Phototaxis and UV Avoidance Behaviors in the Larval Zebrafish.

For many organisms, color is an essential source of information from visual scenes. The larval zebrafish has the potential to be a model for the study of this topic, given its tetrachromatic retina and high dependence on vision. In this study we took a step toward understanding how the larval zebrafish might use color sensing. To this end, we used a projector-based paradigm to force a choice of a color stimulus at every turn of the larva. The stimuli used spanned most of the larval spectral range, including activation of its Ultraviolet (UV) cone, which has not been described behaviorally before. We found that zebrafish larvae swim toward visible wavelengths (>400 nm) when choosing between them and darkness, as has been reported with white light. However, when presented with UV light and darkness zebrafish show an intensity dependent avoidance behavior. This UV avoidance does not interact cooperatively with phototaxis toward longer wavelengths, but can compete against it in an intensity dependent manner. Finally, we show that the avoidance behavior depends on the presence of eyes with functional UV cones. These findings open future avenues for studying the neural circuits that underlie color sensing in the larval zebrafish.

Videoconferencing in psychiatry, a meta-analysis of assessment and treatment.

CONTEXT: Videoconferencing in psychiatry allows psychiatric counseling to be dealt remotely. A number of human randomised clinical trials (RCTs) on this topic were conducted but not systematically analysed since 2005. OBJECTS: A meta-analysis was undertaken to test the hypothesis of non-inferiority of remote psychiatric counseling, including both assessment and treatment, compared to face-to-face setting. Focus of research was the general psychiatric approach, which includes pharmacotherapy, counseling and some not specific psychotherapeutic techniques such as listening, reformulation and clarification among others. Specific forms of psychotherapies were not included in this analysis. DESIGN: RCTs including≥10 subjects per arm were identified in Medline, the Cochrane Library, Embase and the reference list of single papers. A random-effect and a mixed-effect model served for test the hypothesis under analysis. RESULTS: Twenty-six RCTs were included in the analysis, involving 765 (assessment) and 1585 patients (efficacy). The non-inferiority of remote psychiatric counseling was reported both for assessment and treatment. Heterogeneity could not be excluded for assessment, but was excluded for treatment while taking into account clinical and study related variables (P-values=0.003 and 0.06, respectively). CONCLUSION: High levels of consistency between remote and in vivo psychiatric assessment is reported. Efficacy of remote psychiatric counseling was shown to be not inferior compared to in vivo settings. Heterogeneity could not be excluded for assessment, and further analyses are mandatory. The presence of multiple diagnoses included in the analysis was a limit of the present investigation.

PPP3CC gene: a putative modulator of antidepressant response through the B-cell receptor signaling pathway.

Antidepressant pharmacogenetics represents a stimulating, but often discouraging field. The present study proposes a combination of several methodologies across three independent samples. Genes belonging to monoamine, neuroplasticity, circadian rhythm and transcription factor pathways were investigated in two samples (n=369 and 88) with diagnosis of major depression who were treated with antidepressants. Phenotypes were response, remission and treatment-resistant depression. Logistic regression including appropriate covariates was performed. Genes associated with outcomes were investigated in the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) genome-wide study (n=1861). Top genes were further studied through a pathway analysis. In both original samples, markers associated with outcomes were concentrated in the PPP3CC gene. Other interesting findings were particularly in the HTR2A gene in one original sample and the STAR*D. The B-cell receptor signaling pathway proved to be the putative mediator of PPP3CC's effect on antidepressant response (P=0.03). Among innovative candidates, PPP3CC, involved in the regulation of immune system and synaptic plasticity, seems promising for further investigation.

Negative selection and stringency modulation in phage-assisted continuous evolution.

Phage-assisted continuous evolution (PACE) uses a modified filamentous bacteriophage life cycle to substantially accelerate laboratory evolution experiments. In this work, we expand the scope and capabilities of the PACE method with two key advances that enable the evolution of biomolecules with radically altered or highly specific new activities. First, we implemented small molecule-controlled modulation of selection stringency that enables otherwise inaccessible activities to be evolved directly from inactive starting libraries through a period of evolutionary drift. Second, we developed a general negative selection that enables continuous counterselection against undesired activities. We integrated these developments to continuously evolve mutant T7 RNA polymerase enzymes with ∼10,000-fold altered, rather than merely broadened, substrate specificities during a single three-day PACE experiment. The evolved enzymes exhibit specificity for their target substrate that exceeds that of wild-type RNA polymerases for their cognate substrates while maintaining wild type-like levels of activity.

[Podological risk in patients suffering with diabetes in a Bamako health center]. / Risque podologique chez les patients diabetiques dans un centre de sante de reference de Bamako.

PURPOSE: To identify risk factors for foot joint pathologies in diabetic patients at the District I Bamako health center (CSref I). METHODOLOGY: This was a prospective descriptive study from October 2009 to March 2010 at CSref I. The sampling was complete after interrogation, physical and para-clinical examination data were collected and analyzed. The statistical test used was the chi 2 with a significance level p ≤ 0.05. RESULTS: Among the 232 diabetic patients' collected data, female predominance was clear: sex ratio 0.36 with a mean age of 53.03 ± 11.75 years. Physically 58.20% of patients were overweight or obese with diabetes lasting for 5 years in 65.5%. Diabetes was type 2 in 96.1% of cases. The foot lesions were discoverable mode of diabetes in 12.1%. 65.9% of patients were aware of proper foot hygiene procedures but more than half do not practice sufficient hygiene 59.1%. During the study, among the direct risk factors, peripheral sensory neuropathy was more common in the 67.7% and was correlated with patient age (p=0.001), with the duration of the evolution diabetes (p=0.005), with the existence of dyslipidemia (p=0.003) and with poor glycemic balance (p=0.002). Foot deformity existed in 11.6% and type of flat foot, d-hammer toes and Charcot foot. 15.1% of patients had arterial disease that were significantly correlated with the age of patients (p=0.007), disease duration of diabetes (p=0.002), poor glycemic control (p=0.001). Poor venous state exists in 10.34% followed by smoking and alcoholism, respectively 3.88% and 1.29%. Among the foot lesions found, cracks were in 1st place with 22.84% associated or not with other lesions. 1.29% of patients had gangrene. 29.70% of patients had a risk of foot problems in grade 0 70.30% to 10.80% in grade 1 and grade 3 in 9.10%. CONCLUSION: Our diabetic patients had grade 0 in two thirds of cases. The implementation of a program of prevention and early treatment of diabetic foot will often decreased podiatric source of disability risk.

BUT: Identifier les facteurs de risque d'atteinte du pied chez les diabétiques du centre de santé de référence de la commune I de Bamako (CSréf I). MÉTHODOLOGIE: Il s'agissait d'une étude prospective descriptive effectuée d'Octobre 2009 à Mars 2010 au CSréf I. L'échantillonnage était exhaustif après interrogatoire, examen physique et para-clinique, les données ont été recueillies, analysées. Le test statistique utilisé était le Khi 2 avec un seuil de significativité p≤0,05. RÉSULTATS: Parmi les 232 patients diabétiques colligés la prédominance féminine était nette: sex ratio 0,36 , âge moyen de 53,03± 11,75 ans. Au plan physique 58,20% des patients étaient en surpoids ou obèses avec un diabète évoluant depuis 5 ans dans 65,5%. Le diabète était de type 2( 96,1%). Les lésions du pied ont été le mode de découverte du diabète(12,1%). Les patients connaissaient les recommandations sur l'hygiène des pieds dans 65,9% et ils ne le pratiquaient pas dans 59,1% l'hygiène. Parmi les facteurs de risque direct la neuropathie périphérique sensitive était la plus fréquente(67,7%) était liée à l'âge: p=0,001, la durée d'évolution du diabète P=0,005, l'existence d'une dyslipidémie: p=0,003 et le mauvais équilibre glycémique p=0,002. La déformation des pieds existait dans 11,6% à type de pied plat, d-orteils en marteau et de pied de Charcot. L'artériopathie présente chez 15,1% était liéé à l'âge avancé des patients: p=0,007, la durée d'évolution du diabète :p=0,002, au mauvais équilibre glycémique: p=0,001. Le mauvais état veineux existe dans 10,34% suivi du tabagisme et l'alcoolisme dans respectivement 3,88% et 1,29%. Parmi les lésions de pied retrouvées, les crevasses étaient au 1er rang avec 22,84% associées ou non à d'autres lésions. La gangrène était retrouvée chez 1,29% des patients. Chez 29,70% des patients le risque podologique a été gradé: 0(70,30%), 1(10,80%) et 3(9,10%). CONCLUSION: Nos patients diabétiques avaient un grade 0 dans 2/3 des cas. La mise en place d'un programme de prévention et de prise en charge précoce du pied diabétique permettra une diminution du risque podologique source de handicap.

Genomewide interaction and enrichment analysis on antidepressant response.

BACKGROUND: Genomewide association studies (GWASs) on antidepressant efficacy have yielded modest results. A possible reason is that response is influenced by other factors, which possibly interact with genetic variation. We used a GWAS model to predict antidepressant response, by including predictors previously known to affect response, such as quality of life (QoL). We also evaluated the association between genes, previously implicated in gene-environment (G × E) interactions, and response using an enrichment analysis. METHOD: We examined a sample of 1426 depressed patients from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial: 774 responders, 652 non-responders and 418,865 single nucleotide polymorphisms (SNPs) were analysed. First, in a GWAS model, we investigated whether genetic variations interact with patients' levels of QoL to predict response, after controlling for demographic characteristics, severity and population stratification. Second, we conducted an enrichment analysis exploring whether candidate genes that have emerged from prior G × E interaction studies on depression are associated with treatment response. RESULTS: The GWAS model, with QoL as a moderator, yielded one SNP (rs520210) associated with response in the NEDD4L gene (p = 3.64 × 10⁻8). In the Caucasian sample only, we observed a drop in significance for this SNP. The enrichment analysis showed that SNPs within serotonergic genes contained more significant markers that predicted response, compared with a random set of genes in the genome. CONCLUSIONS: Our findings point to possible target genes, which are proposed for further independent replication. Our enrichment analysis provides further support, in a genomewide context, of the role of serotonergic genes in influencing antidepressant response.

DAΦNE operation with electron-cloud-clearing electrodes.

The effects of an electron cloud (e-cloud) on beam dynamics are one of the major factors limiting performances of high intensity positron, proton, and ion storage rings. In the electron-positron collider DAΦNE, namely, a horizontal beam instability due to the electron-cloud effect has been identified as one of the main limitations on the maximum stored positron beam current and as a source of beam quality deterioration. During the last machine shutdown in order to mitigate such instability, special electrodes have been inserted in all dipole and wiggler magnets of the positron ring. It has been the first installation all over the world of this type since long metallic electrodes have been installed in all arcs of the collider positron ring and are currently used during the machine operation in collision. This has allowed a number of unprecedented measurements (e-cloud instabilities growth rate, transverse beam size variation, tune shifts along the bunch train) where the e-cloud contribution is clearly evidenced by turning the electrodes on and off. In this Letter we briefly describe a novel design of the electrodes, while the main focus is on experimental measurements. Here we report all results that clearly indicate the effectiveness of the electrodes for e-cloud suppression.