Guiding Principles for Implementing Stepped Care in Mental Health: Alignment on the Bigger Picture.

Stepped care models are a mental healthcare delivery framework in which a continuum of support allows selection of a range of interventions to match a client's evolving needs and preferences. Currently in use in multiple settings worldwide, stepped care has the potential to provide a needed advance for the development of comprehensive mental health systems. However, definitions of stepped care lack consistency, resulting in differing interpretations reflected in variable implementation, ultimately limiting its replicability, utility and potential for impact. To help foster greater alignment in research and practice, we propose a set of principles for stepped care which can provide guidance on how to bridge multiple mental health services together, reduce fragmentation, and respond to the full breadth of mental health needs along a continuum of care in diverse settings. We hope that articulating these principles will foster discussion and spur mental health stakeholders to translate them into actionable standards.

Efficacy of Hexetidine, Thymol and Hydrogen Peroxide-Containing Oral Antiseptics in Reducing Sars-Cov-2 Virus in the Oral Cavity: A Pilot Study.

BACKGROUND: Studies have demonstrated the role of sputum as a site of severe acute respiratory syndrome-coronavirus-2 (SARSCoV-2) transmission. However, there is limited literature on the virucidal efficacy of oral antiseptics against SARS-CoV-2 virus. This study investigated the virucidal efficacy of three oral-antiseptics compared to a placebo-control in the sputum of SARS-CoV-2 infected individuals. METHODOLOGY: A pilot study of adults with SARS-CoV-2 positive results, as determined by reverse transcription-polymerase chain reaction (RT-PCR) of <7 days. The oral antiseptics investigated were: Hexetidine (0.1% w/v); Thymol (0.063% w/v) and H2O2(1.5%) compared to de-mineralized sterile water (Placebo-control). The primary outcome measure was the proportion of negative RT-PCR results at 15-mins, 30-mins, 1-hour, 2-hours and 4-hours After Oral antiseptics Interventions (AOI) compared to the placebo-control. Statistical analysis was done using STATA 15.0 software with p-values of <0.05 considered statistically significant. RESULTS: Data from a total of 66 participants that were RT-PCR SARS-CoV-2 positive at baseline (0-min) was analysed. At 15-mins AOI, the highest proportion of negativation from sputum samples was observed in the Hexedine group, with 69.2% of the baseline PCR positive cases converting to negative compared to 46.7% in the placebo-control group. In addition, H2O2 demonstrated efficacy at 2-hours AOI compared to placebo-control (62.5% vs 37.5% respectively) and other oral-antiseptics. Across all time-points, the oral-antiseptic groups compared to the placebo-control group, there was no statistically significant difference in the proportion of sputum samples which converted to a negative status (p>0.05). CONCLUSION: The findings in this study suggest there was no significant difference in the proportion of participants who converted to a negative sputum status across the treatment groups at various time points. Future studies could compare the cycle threshold (ct) viral titre values of sputum samples to determine quantitative differences.

CONTEXTE: Des études ont démontré le rôle des expectorations comme un site de transmission du syndrome respiratoire aigu sévère-coronavirus- 2 (SRAS-CoV-2). Cependant, il existe peu de documentation sur l'efficacité virucide des antiseptiques oraux contre le virus du SRASCoV-2. Cette étude a examiné l'efficacité virucide de trois antiseptiques oraux par rapport à un contrôle placebo dans les expectorations de personnes infectées par le SRAS-CoV-2. MÉTHODOLOGIE: Une étude pilote menée auprès d'adultes dont les résultats sont positifs pour le SRAS-CoV-2, tels que déterminés par la réaction en chaîne de la polymérase par transcription inverse (RT-PCR) pendant 7 jours. Les antiseptiques oraux étudiés étaient : Hexetidine (0,1% p/v) ; Thymol (0,063% p/v) et H2O2 (1,5%) par rapport à l'eau stérile déminéralisée (Placebo-contrôle). Le principal critère d'évaluation était la proportion de résultats RT-PCR négatifs 15 minutes, 30 minutes, 1 heure, 2 heures et 4 heures après les interventions antiseptiques orales (AOI) par rapport au contrôle placebo. L'analyse statistique a été réalisée à l'aide du logiciel STATA 15.0, les valeurs p de <0,05 étant considérées comme statistiquement significatives. RÉSULTATS: Les données d'un total de 66 participants qui étaient positifs à la RT-PCR SARS-CoV-2 au départ (0 minute) ont été analysées. Au bout de 15 minutes, la plus forte proportion de négativation des échantillons d'expectoration a été observée dans le groupe Hexedine, 69,2 % des cas positifs au départ par PCR devenant négatifs, contre 46,7 % dans le groupe témoin placebo. En outre, l'H2O2 a démontré son efficacité à 2 heures après l'apparition de la maladie par rapport au groupe placebo (62,5 % contre 37,5 % respectivement) et aux autres antiseptiques oraux. Pour tous les points temporels, les groupes d'antiseptiques oraux comparés au groupe placebo n'ont pas présenté de différence statistiquement significative dans la proportion d'échantillons d'expectoration qui sont devenus négatifs (p>0,05). CONCLUSION: Les résultats de cette étude suggèrent qu'il n'y a pas de différence significative dans la proportion de participants qui sont passés à un statut négatif d'expectoration dans les groupes de traitement à différents moments. Les études futures pourraient comparer les valeurs du titre viral au seuil de cycle (ct) des échantillons d'expectoration afin de déterminer les différences quantitatives. MOTS CLÉS: SRAS-CoV-2, antiseptiques oraux, hexétidine, peroxyde d'hydrogène.

Rapid prototyping of flexible terahertz metasurfaces using a microplotter.

Additive manufacturing is a promising tool for the rapid prototyping of terahertz metamaterials at low-cost. In this letter, a terahertz metamaterial is fabricated using a microplotter system on a flexible polyimide film. The limits of the rapid prototyping technique is investigated both experimentally and numerically in order to determine the spectral range accessible by the fabricated metamaterials. Here, the metamaterial is composed of four arrays of metal-insulator-metal (MIM) antennas exhibiting a Fabry Perot resonance at frequencies from 0.25 to 0.8 THz. From a structural analysis of the printed antennas, we determined that the printing resolution is limited to about 5 µm. The arrays are analyzed by terahertz time-domain spectroscopy (THz-TDS). The good agreement between THz-TDS measurements and numerical simulations showed that the microplotter system can be used for rapid prototyping by adjusting a limited number of fabrication parameters.

Theoretical versus empirical measures of retinal magnification for scaling AOSLO images.

The adaptive optics scanning light ophthalmoscope (AOSLO) allows cellular resolution imaging of the living retina. The accuracy of many quantitative measurements made from these images requires accurate estimates of the lateral scale of the images. Here, we used trial lenses, which are known to affect the relative magnification of the retinal image, to compare empirical measures of image scale with theoretical estimates from a four-surface optical model. The theoretical optical model overestimated the empirically determined change in image scale in 70% of the subjects examined, albeit to varying degrees. While the origin for the differences between subjects is not known, residual accommodation during imaging likely contributes to this variability in retinal magnification. These data provide an opportunity to derive improved lateral scaling error estimates for structural metrics extracted from AOSLO retinal images.

[Lyme disease or not ?] / Maladie de Lyme ou pas ?

Lyme disease is a complex pathology due to an infection by a spirochaete from the genus Borrelia. This infection results from a tick bite lasting more than 24 hours. Signs and symptoms are numerous and are usually classified in three stages: early localized disease, early disseminated disease and late disease. The skin, the heart, the nervous system and the joints are mostly concerned. It is important to distinguish the clinical manifestations of the disease from those that are sometimes associated with it but with no scientific evidence. The purpose of this article is to insist on which signs and symptoms can be related to the disease and on those that usually are not. Diagnostic methods and treatments are also discussed.

La maladie de Lyme est une pathologie complexe, qui résulte d'une infection par un spirochète du genre Borrelia. Cette infection est transmise par une morsure de tique, devant perdurer plus de 24 heures. Les manifestations cliniques de la maladie de Lyme sont nombreuses et classiquement divisées en 3 phases : primaire, secondaire et tertiaire. Elle touche principalement les systèmes cutané, cardiaque, neurologique et articulaire. Il est important de distinguer les manifestations cliniques pouvant être rapportées à cette maladie et celles pour lesquelles aucune évidence scientifique n'a pu être apportée. En effet, il est de plus en plus fréquent que certaines pathologies, dont l'étiologie est incertaine à l'heure actuelle, soient considérées comme provoquées ou secondaires à la borréliose. Cet article vise à faire la lumière sur les symptômes et signes pouvant être attribués à cette affection et ceux qui ne le sont pas. Les méthodes diagnostiques et thérapeutiques seront aussi discutées.

Controlling Nanowire Growth by Light.

Individual Au catalyst nanoparticles are used for selective laser-induced chemical vapor deposition of single germanium nanowires. Dark-field scattering reveals in real time the optical signatures of all key constituent growth processes. Growth is initially triggered by plasmonic absorption in the Au catalyst, while once nucleated the growing Ge nanowire supports magnetic and electric resonances that then dominate the laser interactions. This spectroscopic understanding allows real-time laser feedback that is crucial toward realizing the full potential of controlling nanomaterial growth by light.

The chloroplast genome of the hexaploid Spartina maritima (Poaceae, Chloridoideae): Comparative analyses and molecular dating.

The history of many plant lineages is complicated by reticulate evolution with cases of hybridization often followed by genome duplication (allopolyploidy). In such a context, the inference of phylogenetic relationships and biogeographic scenarios based on molecular data is easier using haploid markers like chloroplast genome sequences. Hybridization and polyploidization occurred recurrently in the genus Spartina (Poaceae, Chloridoideae), as illustrated by the recent formation of the invasive allododecaploid S. anglica during the 19th century in Europe. Until now, only a few plastid markers were available to explore the history of this genus and their low variability limited the resolution of species relationships. We sequenced the complete chloroplast genome (plastome) of S. maritima, the native European parent of S. anglica, and compared it to the plastomes of other Poaceae. Our analysis revealed the presence of fast-evolving regions of potential taxonomic, phylogeographic and phylogenetic utility at various levels within the Poaceae family. Using secondary calibrations, we show that the tetraploid and hexaploid lineages of Spartina diverged 6-10 my ago, and that the two parents of the invasive allopolyploid S. anglica separated 2-4 my ago via long distance dispersal of the ancestor of S. maritima over the Atlantic Ocean. Finally, we discuss the meaning of divergence times between chloroplast genomes in the context of reticulate evolution.

The anti-inflammatory and antioxidant activity of 25 plant species used traditionally to treat pain in southern African.

BACKGROUND: Inflammation is a common risk factor in the pathogenesis of conditions such as infections, arthritis, type 2 diabetes mellitus, obesity and cancer. An ethnobotanical survey of medicinal plants used traditionally to treat inflammation and related disorders such as pain, arthritis and stomach aches in southern Africa led to the selection of 25 plant species used in this study. METHODS: The antioxidant activities of acetone extracts were determined by measuring the free radical scavenging activity and ferric reducing ability, respectively. The anti-inflammatory activities of the extracts were determined by measuring the inhibitory effect of the extracts on the activities of the pro-inflammatory enzyme, lipoxygenase and inducible nitric oxide synthase. RESULTS: Extracts of Peltophorum africanum had good antioxidant activity with IC50 values of 4.67 ± 0.31 µg/mL and 7.71 ± 0.36 µg/mL compared to that of the positive control ascorbic acid (2.92 ± 0.14 µg/mL and 13.57 ± 0.44 µg/mL), using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and 2,2'-azinobis (3-ethylbenzthiazoline-6-sulphonic acid (ABTS) methods, respectively. The metabolism of linoleic acid to leukotriene derivatives by 15-lipoxygenase (15-LOX) was also inhibited by the crude acetone extracts of Peltophorum africanum (IC50 = 12.42 µg/mL), Zanthoxylum capense (IC50 = 14.92 µg/mL) compared to the positive control quercetin (IC50 = 8.75 µg/mL). There was a poor correlation between the flavonoid content and 15-LOX inhibition by the extracts (R(2) = 0.05), indicating that flavonoids are not involved in LOX inhibition. Extracts of Clausena anisata, at a concentration of 6.25 µg/mL inhibited nitric oxide production by RAW 264.7 macrophage cell lines in vitro by 96 %. The extracts of Zanthoxylum capense were the least cytotoxic (IC50 > 1000 µg/mL) when the extract toxicity was determined against Vero (African green Monkey) kidney cell lines. CONCLUSION: Some plant species used traditionally to treat pain have reasonable anti-inflammatory activity and flavonoids are probably not involved in this process.

Exploring the genome of the salt-marsh Spartina maritima (Poaceae, Chloridoideae) through BAC end sequence analysis.

Spartina species play an important ecological role on salt marshes. Spartina maritima is an Old-World species distributed along the European and North-African Atlantic coasts. This hexaploid species (2n = 6x = 60, 2C = 3,700 Mb) hybridized with different Spartina species introduced from the American coasts, which resulted in the formation of new invasive hybrids and allopolyploids. Thus, S. maritima raises evolutionary and ecological interests. However, genomic information is dramatically lacking in this genus. In an effort to develop genomic resources, we analysed 40,641 high-quality bacterial artificial chromosome-end sequences (BESs), representing 26.7 Mb of the S. maritima genome. BESs were searched for sequence homology against known databases. A fraction of 16.91% of the BESs represents known repeats including a majority of long terminal repeat (LTR) retrotransposons (13.67%). Non-LTR retrotransposons represent 0.75%, DNA transposons 0.99%, whereas small RNA, simple repeats and low-complexity sequences account for 1.38% of the analysed BESs. In addition, 4,285 simple sequence repeats were detected. Using the coding sequence database of Sorghum bicolor, 6,809 BESs found homology accounting for 17.1% of all BESs. Comparative genomics with related genera reveals that the microsynteny is better conserved with S. bicolor compared to other sequenced Poaceae, where 37.6% of the paired matching BESs are correctly orientated on the chromosomes. We did not observe large macrosyntenic rearrangements using the mapping strategy employed. However, some regions appeared to have experienced rearrangements when comparing Spartina to Sorghum and to Oryza. This work represents the first overview of S. maritima genome regarding the respective coding and repetitive components. The syntenic relationships with other grass genomes examined here help clarifying evolution in Poaceae, S. maritima being a part of the poorly-known Chloridoideae sub-family.

Allogeneic stem cell transplantation for patients with advanced rhabdomyosarcoma: a retrospective assessment.

BACKGROUND: Allogeneic haematopoietic stem cell transplantation (allo-SCT) may provide donor cytotoxic T cell-/NK cell-mediated disease control in patients with rhabdomyosarcoma (RMS). However, little is known about the prevalence of graft-vs-RMS effects and only a few case experiences have been reported. METHODS: We evaluated allo-SCT outcomes of 30 European Group for Blood and Marrow Transplantation (EBMT)-registered patients with advanced RMS regarding toxicity, progression-free survival (PFS) and overall survival (OS) after allo-SCT. Twenty patients were conditioned with reduced intensity and ten with high-dose chemotherapy. Twenty-three patients were transplanted with HLA-matched and seven with HLA-mismatched grafts. Three patients additionally received donor lymphocyte infusions (DLIs). Median follow-up was 9 months. RESULTS: Three-year OS was 20% (s.e.±8%) with a median survival time of 12 months. Cumulative risk of progression was 67% (s.e.±10%) and 11% (s.e.±6%) for death of complications. Thirteen patients developed acute graft-vs-host disease (GvHD) and five developed chronic GvHD. Eighteen patients died of disease and four of complications. Eight patients survived in complete remission (CR) (median: 44 months). No patients with residual disease before allo-SCT were converted to CR. CONCLUSION: The use of allo-SCT in patients with advanced RMS is currently experimental. In a subset of patients, it may constitute a valuable approach for consolidating CR, but this needs to be validated in prospective trials.

Transcriptome de novo assembly from next-generation sequencing and comparative analyses in the hexaploid salt marsh species Spartina maritima and Spartina alterniflora (Poaceae).

Spartina species have a critical ecological role in salt marshes and represent an excellent system to investigate recurrent polyploid speciation. Using the 454 GS-FLX pyrosequencer, we assembled and annotated the first reference transcriptome (from roots and leaves) for two related hexaploid Spartina species that hybridize in Western Europe, the East American invasive Spartina alterniflora and the Euro-African S. maritima. The de novo read assembly generated 38 478 consensus sequences and 99% found an annotation using Poaceae databases, representing a total of 16 753 non-redundant genes. Spartina expressed sequence tags were mapped onto the Sorghum bicolor genome, where they were distributed among the subtelomeric arms of the 10 S. bicolor chromosomes, with high gene density correlation. Normalization of the complementary DNA library improved the number of annotated genes. Ecologically relevant genes were identified among GO biological function categories in salt and heavy metal stress response, C4 photosynthesis and in lignin and cellulose metabolism. Expression of some of these genes had been found to be altered by hybridization and genome duplication in a previous microarray-based study in Spartina. As these species are hexaploid, up to three duplicated homoeologs may be expected per locus. When analyzing sequence polymorphism at four different loci in S. maritima and S. alterniflora, we found up to four haplotypes per locus, suggesting the presence of two expressed homoeologous sequences with one or two allelic variants each. This reference transcriptome will allow analysis of specific Spartina genes of ecological or evolutionary interest, estimation of homoeologous gene expression variation using RNA-seq and further gene expression evolution analyses in natural populations.

Effectiveness of 11C-choline PET/CT in prostate cancer surveillance.

AIM: Our aim was to analyse the performance of [11C]choline PET/CT in prostate cancer (PCa) surveillance, especially in patients with prostate specific antigen (PSA) < 1 ng/mL. MATERIAL AND METHODS: Three hundred and twenty-nine [11C]choline PET/CT examinations from 191 patients (68.2 ±â€¯7.2 years) submitted for PCa surveillance or biochemical recurrence were retrospectively evaluated. PSA at study was 13.0 ±â€¯84.2 ng/mL. Main initial treatment was radical prostatectomy (RP) in 81 patients, and other treatments (radiotherapy, chemotherapy, hormonotherapy) in 110. PET/CT was acquired 20' after injection of 555-740 MBq of [11C]choline. Minimum follow-up was 12 months. RESULTS: Two hundred and nineteen (66.6%) out of the 329 PET/CT examinations were positive. The percentage of positive examinations was significantly higher in patients with other initial treatment than RP compared to patients with RP (85.6% vs. 43.6%, respectively). One hundred and thirty PET/CT (59.4%) showed local recurrence, 48 (21.9%) distant recurrence, and 41 (18.7%) local plus distant recurrence. Initial therapeutic approach was changed in 139 cases (63.5%). In the subgroup of 81 [11C]choline PET/CT scans performed with PSA < 1 ng/mL, 23 (28.4%) showed a positive result. Initial therapeutic approach was changed in 9 (11.1%). Three (4.8%) out of 63 patients died as per PCa. CONCLUSION: [11C]choline PET/CT demonstrated its effectiveness in PCa surveillance and restaging, even in patients with serum PSA < 1 ng/mL. The diagnostic performance was different depending on the initial treatment, been higher in patients with non-surgical treatment.

No improvement of survival with reduced- versus high-intensity conditioning for allogeneic stem cell transplants in Ewing tumor patients.

BACKGROUND: Outcomes of Ewing tumor (ET) patients treated with allogeneic stem cell transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts. PATIENTS AND METHODS: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts. RESULTS: Median overall survival was 7.9 months [±1.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (±1.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE). CONCLUSIONS: There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocols.

Impaired vascular permeability regulation caused by the VEGF165b splice variant in pre-eclampsia.

OBJECTIVE: Pre-eclampsia is diagnosed by hypertension and proteinuria, probably caused by endothelial dysfunction, resulting in symptoms including oedema, inflammation and altered metabolism. Vascular endothelial growth factor A (VEGF-A) is detected at higher concentrations in plasma from patients with pre-eclampsia than in plasma from normotensive pregnant patients when determined by radioimmunoassay. This study tested the hypothesis that circulating VEGF-A in pre-eclamptic plasma is biologically active in vivo, and aimed to identify specific isoforms responsible for this activity. DESIGN: Plasma from pre-eclamptic (n = 17) and normotensive (n = 10) pregnant women was perfused into Rana mesenteric microvessels, and the subsequent change in microvascular permeability was measured using a single-vessel perfusion micro-occlusion technique. RESULTS: Pre-eclamptic but not normotensive plasma resulted in a 5.25 ± 0.8-fold acute increase in vascular permeability (P = 0.0003). This increase could be blocked by the incubation of plasma with bevacizumab, an antibody to VEGF-A (n = 7; P = 0012), and by VEGF-A receptor inhibition by SU5416 at doses specific to VEGF-A receptor-1 (VEGFR1), but not by the VEGF-A receptor-2 inhibitor, ZM323881. Although VEGF(165) b levels were not significantly altered in the PET samples, the increase in permeability was also inhibited by incubation of pre-eclamptic plasma with an inhibitory monoclonal antibody specific for VEGF165b (n=6; P<0.01), or by the addition of placental growth factor 1 (PlGF-1; n = 3; P < 0.001). PlGF-1 was detected at lower concentrations in pre-eclamptic plasma than in normotensive plasma. CONCLUSIONS: These findings suggest that circulating VEGF-A levels in pre-eclampsia are biologically active because of a loss of repression of VEGFR1 signalling by PlGF-1, and VEGF165b may be involved in the increased vascular permeability of pre-eclampsia.

Germline mutations of the CBL gene define a new genetic syndrome with predisposition to juvenile myelomonocytic leukaemia.

BACKGROUND: CBL missense mutations have recently been associated with juvenile myelomonocytic leukaemia (JMML), an aggressive myeloproliferative and myelodysplastic neoplasm of early childhood characterised by excessive macrophage/monocyte proliferation. CBL, an E3 ubiquitin ligase and a multi-adaptor protein, controls proliferative signalling networks by downregulating the growth factor receptor signalling cascades in various cell types. METHODS AND RESULTS: CBL mutations were screened in 65 patients with JMML. A homozygous mutation of CBL was found in leukaemic cells of 4/65 (6%) patients. In all cases, copy neutral loss of heterozygosity of the 11q23 chromosomal region, encompassing the CBL locus, was demonstrated. Three of these four patients displayed additional features suggestive of an underlying developmental condition. A heterozygous germline CBL p.Y371H substitution was found in each of them and was inherited from the father in one patient. The germline mutation represents the first hit, with somatic loss of heterozygosity being the second hit positively selected in JMML cells. The three patients display a variable combination of dysmorphic features, hyperpigmented skin lesions and microcephaly that enable a 'CBL syndrome' to be tentatively delineated. Learning difficulties and postnatal growth retardation may be part of the phenotype. CONCLUSION: A report of germline mutations of CBL in three patients with JMML is presented here, confirming the existence of an unreported inheritable condition associated with a predisposition to JMML.

Ethnomedicinal uses, biological activities, phytochemistry and conservation of African ginger (Siphonochilus aethiopicus): A commercially important and endangered medicinal plant.

ETHNOPHARMACOLOGICAL RELEVANCE: In sub-Saharan Africa, African ginger (Siphonochilus aethiopicus) is used for treating common illnesses including colds, coughs, inflammation and related symptoms. The available literature survey on this plant provided scarce anecdotal information, particularly in western and eastern Africa, with a few reports on its bioactivity. In addition, the indigenous knowledge and conservation strategies of this economically important and critically endangered species are currently fragmented. AIM OF THE REVIEW: This review entails a critical appraisal of existing literature on the ethnomedicinal uses, biological activities, phytochemicals, research opportunities and prospects for the sustainable use of S. aethiopicus. MATERIALS AND METHODS: This review was conducted using a comprehensive literature search on the ethnomedicinal uses, biological activities and phytochemistry of S. aethiopicus throughout its distributional range. The conservation status and associated bio-economy potential of African ginger were also assessed. We searched different online databases (e.g. Google Scholar, ScienceDirect, PubMed and Scopus) for peer-reviewed journals, conference outputs, international, regional and national organizational reports, published books and theses. RESULTS: We established that S. aethiopicus is used to treat a wide variety of ailments such as respiratory problems (including cough, influenza), pain, inflammation and malaria. Extracts of African ginger are used as an ingredient in some commercialised products for nutraceutical, cosmeceutical and pharmaceutical purposes. The rhizome extract demonstrated anti-asthmatic, anti-inflammatory, and antiplasmodial activities, which led to the development of a patented novel extract for treating asthma and allergies. Phytochemical analysis of leaf, root and rhizome extracts of African ginger revealed the presence of flavonoids, phenolic acids, volatile and essential oils as the major constituents. These phytochemicals are known to possess bioactivities such as antimicrobial and anti-inflammatory activities. Particularly, the bioactive compounds, siphonochilone and eucalyptol, found in the roots and rhizomes have demonstrated potential to be used in remedies for treating asthma and allergic reactions. Furthermore, extracts of S. aethiopicus contained natural anti-inflammatory mediators with potential to combat and manage chronic inflammation. This plant is classified on the Red List of South African Plants as a critically endangered plant. Its high risk of extinction due to its unsustainable harvesting and exploitation necessitates its rapid propagation and cultivation to meet its increasing demand. CONCLUSIONS: The review highlights the therapeutic potential of S. aethiopicus and rational prioritization of this plant species with the potential for isolating new bioactive compounds. In the light of the use of this plant extract in traditional medicine and many commercial products, there is a heightened need to explore the mechanism(s) of action of the identified extracts and bioactive compounds in order to fully understand their pharmacokinetics and probably elucidate the pathways of their activities.

Evidence of a clinical response at one yr after reduced-intensity allogeneic hematopoietic stem cell transplantation in heavily pretreated adolescents with aggressive refractory Hodgkin's lymphoma.

We report results of RIC AHSCT in four adolescents with aggressive refractory HL. They all received three or four lines of therapy prior to RIC-AHSCT including autografts. At the time of RIC, they were in partial response except for one patient who had progressive chemoresistant disease. The conditioning regimen consisted of fludarabin, busulfan and ATG. They all had a matched related donor. The median follow-up was 12-16-month post-allograft. All patient transplants engrafted rapidly. The median time of hospitalization was 35 days. The median time to neutrophil recovery (>or=500/muL) was 19 days. All the patients were in complete donor chimerism at day 60. Four patients developed skin (grade

Grewia mollis Leaf Extracts and Fractions Demonstrated Good Inhibitory Activity on Pro-Inflammatory Enzymes and with Lower Cytotoxicity in vitro.

INTRODUCTION: Plant extracts are used to treat illnesses, promote health, and maintain general well-being in traditional medicine. Grewia mollis Juss (Malvaceae) is one of the medicinal herbs that is used traditionally to treat chronic diseases and related pain because currently used anti-inflammatory drugs may cause severe side effects, and naturally occurring compounds with reduced cytotoxicity could be explored for therapeutic goals. MATERIALS AND METHODS: Dried leaf of G. mollis was extracted with aqueous and organic solvents and partitioned based on polarity using solvent-solvent methods. The extracts were tested in anti-inflammatory assays against cyclooxygenases and lipoxygenase, and the safety profile was determined in a cell-based in-vitro assay. RESULTS: The n-hexane fraction of G. mollis leaf extracts had significant activity against both COX-1 (IC50 =0.97±1.9 µg/mL) and COX-2 (IC50 =1.13±0.2 µg/mL) better than the indomethacin positive control (IC50 =1.3±0.6 and 1.52±0.2 µg/mL), respectively (p≤ 0.05). Also, all the extracts and fractions of G. mollis tested inhibited the activity of 15-LOX (IC50 =12.48±2.9 to 29.43±9.9 µg/mL) better than the quercetin reference control (IC50 =61.82±5.5 µg/mL), with the butanol fraction demonstrating the best anti-15 LOX action (IC50 =12.48±2.9 µg/mL). Furthermore, all the extracts and fractions of G. mollis had relatively lower cytotoxicity on vero monkey kidney cells (LD50 =30.56-479±0.07 µg/mL) compared to the doxorubicin positive control (LD50 =2.59 µg/mL), but the selectivity index (SI=1.04-1.89) determination suggested that some of the extracts may contain toxic constituents. CONCLUSION: Organic extracts of the leaves of Grewia mollis contained bioactive molecules with potent action on COX-2 and 15-LOX. Targeted high-resolution high-performance liquid chromatographic (HPLC) methods have streamlined and enhanced bioactive compound isolation and purification process. This allows for the separation of undesirable compounds that could cause metabolic cytotoxicity in the plant extract mixtures. The method could be used to develop an alternative therapeutic strategy to manage pain associated with chronic inflammation where the use of NSAID is problematic.

[The immunohistochemical expression of cyclin B1 is associated with higher SUV in 18F-FDG-PET in non-small cell lung cancer patients. Initial results]. / La expresión inmunohistoquímica de ciclina B1 conlleva mayores valores de SUV en la 18F-FDG-PET de pacientes con carcinomas no microcíticos de pulmón. Primeros resultados.

AIM: to study the expression of cyclin B1 and its possible relationship with the maximum SUV in FDG-PET and MIB1 expression in patients with NSCLC. MATERIALS AND METHODS: 49 patients (15 adenocarcinomas, 27 squamous cell carcinomas and 7 bronchoalveolar carcinomas) were included in this study; the immunohistochemical expression of cyclin B1 was determined using the tissue-array technique. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. RESULTS: cyclin B1 expression was detected in 40 out of 45 cases. The SUV values were higher (p=0.04) in the cyclin B1+ cases than in the negative cases (16.4+/-8.1 vs 10.9+/-6.2). Cyclin B1 expression and SUV values were not correlated with the clinical stage. The expression of cyclin B1+ correlated positively (p<0.0001) with that of MIB1. After univariate analysis, only the cellular proliferation was a prognostic factor (p=0.037). CONCLUSIONS: our results suggest that there is a direct correlation between cyclin B1 expression and max-SUV values in the PET of NSCLC patients. When the association of cyclin B1 with positive MIB1 is also considered, our results support the role of cell proliferation in FDG uptake by the tumour.

[The immunohistochemical expression of cyclooxygenase 2 is inversely associated with (18)F-FDG-PET SUV values in non-small-cell lung cancers. Initial results]. / La expresión inmunohistoquímica intensa de ciclooxigenasa 2 se asocia inversamente con los valores máximos de SUV en la (18)F-FDG-PET de pacientes afectados de carcinomas no microcíticos de pulmón. Relación con otros factores biológicos.

OBJECTIVE: To study the expression of COX-2 and its possible relationship with the maximum standardized uptake value (SUV) in FDG-PET, and EGFR, p16 and MIB1 expression in patients with NSCLC. MATERIAL AND METHOD: 45 patients (12 adenocarcinomas and 33 squamous cell carcinomas) were included in this study; the immunohistochemical expression of COX-2, MIB-1, p16 and EGFR was determined using tissue-array. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. RESULTS: COX-2 expression was detected in 35 out of 45 cases, and was very significant (> ++) in 12 of them. SUV values were lower in the COX-2 > ++ cases that in the remaining cases (13.4 +/- 1.2 vs. 12.9 vs. 17.1 +/- 1.5; p = 0.059). COX-2 > ++ expression and maxSUV values were not correlated with the clinical stage. The expression of COX-2 > ++ was correlated positively with p16 (r = 0.36; p = 0.014) and negatively with MIB1 (r = -0.32; p = 0.041) expression, whereas the SUV was correlated positively with EGFR (r = 0.44; p = 0.004) and negatively with p16 (r = -0.29; p = 0.041) expression. CONCLUSIONS: Our results suggest that: a) the expression of COX-2 > ++ is often found in this kind of lung cancer and is not associated with the clinical stage; b) the maxSUVs were not related to the stage and were lower in COX-2 > ++ tumours than in the other cases; and c) the different behaviour of both parameters can be explained by their correlation with cell proliferation (MIB1), EGFR and p16 expression.