A clinical-pharmaceutical medication reconciliation with patient interview for a medication review to identify drug-related problems in elective patients during hospital admission.

Background and aim: Drug-related problems (DRPs), e.g.drug-drug interactions (DDI), can lead to adversedrug reactions (ADRs) and thus complications during hospitalization. For this reason, such DRP, DDI and ADR should be identified and characterized as early as possible during hospital admission. We aimed to perform a clinical-pharmaceutical medication reconciliation in which patient-related information was collected and compared to drug-related information in a medication review. Investigations: During a 24-week-period, we consecutively invited patients electively admitted to Urology, Otolaryngology, Oral and Maxillofacial Surgery, General and Visceral Surgery, and Oncology Departments of a 300-bed hospital. A clinical pharmacist performed a patient interview asking for medication, ADR, and adherence. The medication reconciliation considered packages for a brown-bag analysis, medication lists, and data from the clinical information-system (CIS). In a medication review, we matched patient-related information to drug-related information from the drug label, guidelines, drug-databases and websites to identify DRPs. Results: In the study, 356 patients (median age: 58 years) taking 1,712 drugs participated. Of all patients, 7.3% reported ADR and 10.7% missing adherence. 5.3% brought packages that enabled a brown-bag analysis and 21.1% a medication list. In 76.7% of patients, information from CIS was incomplete or not up-to-date. Among the most frequently identified DRPs were "Medication without diagnosis" (31.2%) and "Inappropriate timing of administration" (11.5%). The proportion of patients affected by severe DDI ranged from 0.8%-16.6%, depending on the drug information source. Conclusions: Incomplete patient data, frequently identified DRPs and inconsistent drug-based information make pharmaceutical involvement in medication reconciliation on admission a necessity.

International Standardized Nomenclature for Outbred Stocks of Laboratory Animals.

In accordance with the «Aims of ICLA¼ (ICLA Bulletin No. 26, March 1970) the Governing Board established in 1969 a Working Party to prepare an International Nomenclature System for Outbred Animals. The members were: Professor, Dr. A. Spiegel, Federal Republic of Germany, chairman.Dr. M. Festing, United KingdomDr. K. Kondo, JapanDr. R. Loosli, SwitzerlandMr. S. Poiley, U.S.A. The nomenclature rules, completed and approved by the ICLA Governing Board on 8 December 1971, are published herewith. I am convinced that this system will bring order out of the existing chaos. The system is an offer to the world laboratory animal science, particularly the breeders and users. Editors of scientific journals, catalogues, and indices all over the world are also encouraged to require and use animal stock identification by this system for outbred animals used in experimentation. The ICLA Governing Board would have preferred to have seen an international centralization of symbol registration. However, the ICLA Secretariat has not got the capacity necessary for such a task and some practical solution to the registration problem will have to be found by the Governing Board. A final aim should then be for ICLA to publish a comprehensive world list of breeder symbols at intervals. Oslo, January 1972 Stian Erichsen  Secretary-General.

Impact of Covid-19 on farming systems in Europe through the lens of resilience thinking.

Context: Resilience is the ability to deal with shocks and stresses, including the unknown and previously unimaginable, such as the Covid-19 crisis. Objective: This paper assesses (i) how different farming systems were exposed to the crisis, (ii) which resilience capacities were revealed and (iii) how resilience was enabled or constrained by the farming systems' social and institutional environment. Methods: The 11 farming systems included have been analysed since 2017. This allows a comparison of pre-Covid-19 findings and the Covid-19 crisis. Pre-Covid findings are from the SURE-Farm systematic sustainability and resilience assessment. For Covid-19 a special data collection was carried out during the early stage of lockdowns. Results and conclusions: Our case studies found limited impact of Covid-19 on the production and delivery of food and other agricultural products. This was due to either little exposure or the agile activation of robustness capacities of the farming systems in combination with an enabling institutional environment. Revealed capacities were mainly based on already existing connectedness among farmers and more broadly in value chains. Across cases, the experience of the crisis triggered reflexivity about the operation of the farming systems. Recurring topics were the need for shorter chains, more fairness towards farmers, and less dependence on migrant workers. However, actors in the farming systems and the enabling environment generally focused on the immediate issues and gave little real consideration to long-term implications and challenges. Hence, adaptive or transformative capacities were much less on display than coping capacities. The comparison with pre-Covid findings mostly showed similarities. If challenges, such as shortage of labour, already loomed before, they persisted during the crisis. Furthermore, the eminent role of resilience attributes was confirmed. In cases with high connectedness and diversity we found that these system characteristics contributed significantly to dealing with the crisis. Also the focus on coping capacities was already visible before the crisis. We are not sure yet whether the focus on short-term robustness just reflects the higher visibility and urgency of shocks compared to slow processes that undermine or threaten important system functions, or whether they betray an imbalance in resilience capacities at the expense of adaptability and transformability. Significance: Our analysis indicates that if transformations are required, e.g. to respond to concerns about transnational value chains and future pandemics from zoonosis, the transformative capacity of many farming systems needs to be actively enhanced through an enabling environment.

Better early outcome with enteral rather than parenteral nutrition in children undergoing MAC allo-SCT.

There is no consensus on the type of nutritional support to introduce in children undergoing allogeneic stem cell transplantation (allo-SCT) after myeloablative conditioning (MAC). This retrospective, multicenter, observational study compared the early administration of enteral nutrition (EN group, n = 97) versus parenteral nutrition (PN group, n = 97) in such patients with matching for important covariates. The primary endpoint was the study of day 100 overall mortality. The early outcome at day 100 was better in EN group regarding mortality rate (1% vs. 13%; p = 0.0127), non relapse mortality (1% vs. 7%; p = 0.066), acute GVHD grades II-IV (37% vs. 54%; p = 0.0127), III-IV (18% vs. 34%; p = 0.0333) and its gut localization (16% vs. 32%; p = 0.0136). Platelet engraftment was better in EN group than in PN group for the threshold of 20 G/L (97% vs. 80% p < 0.0001) and 50 G/L (92% vs. 78%, p < 0.0001). The length of stay was shorter in EN group (28 vs. 52 days, p < 0.0001). There were no differences between the two groups regarding the polynuclear neutrophil engraftment, infection rate or mucositis occurrence. These results suggest that, in children undergoing MAC allo-SCT, PN should be reserved to the only cases when up-front EN is insufficient or impossible to perform.

Sensory recovery of the breast after innervated and non-innervated autologous breast reconstructions: A systematic review.

BACKGROUND: The sensory recovery of the reconstructed breast is an undervalued topic in the field of autologous breast reconstruction. This systematic review aimed to evaluate the available literature on the sensory recovery of the breast after innervated and non-innervated autologous breast reconstructions and to assess the possible benefits of sensory nerve coaptation compared to spontaneous reinnervation of the flap. METHODS: A comprehensive literature search was conducted in PubMed, Embase and the Cochrane Library to identify all eligible studies regarding the sensory recovery of all types of innervated and non-innervated autologous breast reconstructions. RESULTS: The search yielded 334 hits, of which 32 studies concerning 1177 breast reconstructions were included. The amount of heterogeneity between the studies was high, which made the pooling of data difficult. The studies indicated that spontaneous reinnervation of autologous breast reconstructions occurred to a variable extent, depending on how and when it was measured. Despite these variable results, the sensory recovery of innervated flaps, however, was superior, started earlier and gradually improved over time with a higher chance of approaching normal values than non-innervated flaps. There is a lack of studies that assess the return of erogenous sensation and quality of life. CONCLUSION: The current evidence shows that nerve coaptation results in superior sensory recovery of the reconstructed breast compared to spontaneous reinnervation of the flap. This review illustrates that more standardised, high-quality studies with adequate sample sizes are needed to objectively evaluate the sensory recovery of the breast after autologous breast reconstructions.

[Pediatric medulloblastoma: Retrospective series of 52 patients]. / Médulloblastomes de l'enfant: étude rétrospective portant sur 52 patients.

PURPOSE: Retrospective analysis of the results of 52 children irradiated for a medulloblastoma. PATIENTS AND METHODS: Between 1974 and 2012, 52 children with an average age of 6 years and a half (11 months-17 years and a half) were treated with surgery then with radiotherapy at the Comprehensive Cancer Centre of Strasbourg (France). For 44 children, the treatment consisted of a chemotherapy. RESULTS: After a mean follow-up of 106.6 months (7-446 months), 13 relapses and 24 deaths were observed. Overall survival at 5 years and 10 years were 62% and 57%, respectively. Disease-free survival at 5 years and 10 years were 80% and 63%, respectively. Univariate analysis found the following adverse prognostic factors: the existence of a postoperative residue, the positivity of the cerebrospinal fluid, the metastatic status and medulloblastoma of high-risk. Positivity of the cerebrospinal fluid remains a negative factor in multivariate analysis. CONCLUSION: These results confirm the survival rate obtained by a conventional approach (surgery then irradiation). Insufficiency of results and rarity of medulloblastoma require the establishment of international protocols.

[Evolution of the management of pediatric and adult medulloblastoma]. / Évolution de la prise en charge des médulloblastomes de l'enfant et de l'adulte.

Medulloblastoma are cerebellar tumours belonging to the group of primitive neuroectodermal tumours (PNET) and are the most common malignant brain tumours of childhood. These tumours are rare and heterogeneous, requiring some multicentric prospective studies and multidisciplinary care. The classical therapeutic approaches are based on clinical, radiological and surgical data. They involve surgery, radiation therapy and chemotherapy. Some histological features were added to characterize risk. More recently, molecular knowledge has allowed to devise risk-adapted strategies and helped to define groups with good outcome and reduce long-term sequelae, improve the prognostic of high-risk medulloblastoma and develop new therapeutic tools.

[Biomechanical testing of a new total wrist arthrodesis plate]. / Biomechanische Testung einer neuen Handgelenkarthrodesenplatte.

PURPOSE: The aim of this study was to evaluate the biomechanical properties of the APTUS wrist fusion plate in comparison to those of the AO wrist fusion plate. MATERIAL AND METHOD: 6 APTUS wrist fusion plates (APTUS 2.5 TriLock Wrist Fusion Plate Long Bend) from Medartis (Basel, Switzerland) and 6 AO wrist fusion plates (= LCP Wrist Fusion Plate Standard Bend from Dupuy-Synthes, Bettlach, Switzerland) were installed according to the manufacturers' instructions on life-sized, fibre-glass reinforced polyamide models of a healthy human hand. Then fatigue testing with increasing loads on a monoaxial material testing machine was carried out and the force-movement measurements were recorded on a PC. For up to 50,000 cycles, loading was applied in a sinus-wave frequency of 4 Hz and a force ratio (FMin/FMax) of 0.1-70 N. After 50,000 cycles and then at every 10,000 cycles the load was increased by 15% until breakage or a deformation of over 15 mm at the point of force application of the implant occurred. In addition, the tear-out resistance of 5 screws of each type of plate was examined and the system tear-out resistance calculated. The mean values and standard deviations of fatigue strength, torsional moments and fatigue limits (load cycles) were checked for normal distribution and finally the results were compared by means of non-parametric and parametric statistical tests. RESULTS: Plate breakage occurred with the AO wrist fusion plate on average after 52,596 (SD±12,833) load cycles and with the APTUS wrist fusion plate after an average of 115,428 (SD±12,600) load cycles. For the AO wrist fusion plates, an average load of 6.3 (SD±0.8) Nm and for the APTUS plate one of 10 (SD±1.7) Nm led to failure. For the APTUS plate the screw tear-out resistance was calculated as 2,632 (SD±96) N while that for the AO plate was found to be 1,449 (SD±314) N. CONCLUSION: In comparison to the AO wrist fusion plate the APTUS wrist fusion plate has significantly higher fatigue resistance and tear-out strength. On the basis of 100,000 load cycles until bone healing in the case a wrist arthrodesis, use of the APTUS plate should enable bone healing to occur before the implant fails.

Adverse events following vaccination in the French armed forces: An overview of surveillance conducted from 2002 to 2010.

French military personnel are subject to a compulsory vaccination schedule. The aim of this study was to describe vaccine adverse events (VAE) reported from 2002 to 2010 in armed forces. VAE are routinely surveyed by the military Centre for epidemiology and public health. For each case, military practitioners fill a notification form, providing patient characteristics, clinical information and vaccines administered. For this study, VAE following influenza A(H1N1)pdm09 vaccination were excluded. Among the 473 cases retained, 442 (93%) corresponded to non-severe VAE,including local, regional and systemic events, while 31 corresponded to severe VAE, with two leading to significant disability. The global VAE reporting rate (RR) was 14.0 per 100,000 injections. While stationary from 2002 to 2008, the RR increased from 2009. The most important observations were a marked increase of VAE attributed to Bacillus Calmette-Guérin (BCG) vaccine from 2005 to 2008, a high RR observed with the inactivated diphtheria-tetanus (toxoids)-poliovirus vaccine combined with acellular pertussis vaccine (dTap-IPV) from 2008 and an increase in RR for seasonal influenza vaccine VAE in 2009. Our RR for severe VAE (1.1 VAEper 100,000) appears comparable with rates observed among United States civilians and military personnel. The increase observed from 2009 could be partly explained by the influenza A(H1N1)pdm09 pandemic which increased practitioner awareness towards VAE. In conclusion, the tolerance of the vaccines used in French armed forces appears acceptable.

Investigation on a pertussis outbreak in a military school: risk factors and approach to vaccine efficacy.

INTRODUCTION: Pertussis (whooping cough) is a toxic bacterial infection caused mainly by Bordetella pertussis. In mid-January 2006, several cases of pertussis were diagnosed in a military boarding-school. An investigation was carried out at the end of January to identify the risk factors for infection and to evaluate the efficacy of vaccination. SUBJECTS AND METHODS: Three definitions were used to distinguish the cases; confirmed biologically, confirmed epidemiologically and suspected cases. The risk factor study was carried out after the exclusion of suspect cases. Vaccine efficacy (VE) was evaluated from a case-control study where only biologically confirmed cases were included. For each case, five controls were matched according to age, sex and class. A logistic regression and a conditional logistic regression were performed for the risk factor study and vaccine efficacy, respectively. Statistical analysis was carried out using Stata 9.2 software. RESULTS: A total of 206 cases were included, 17 of them biologically confirmed, 66 epidemiologically and 123 suspected cases. The attack rate was 17.8 per 100. Girls were 1.8 times more likely to catch pertussis (p=0.04), pupils in the first year of college, as well as those in high school were at 5 times greater risk of catching pertussis (p=0.008) than those in the second year of college. For pupils who benefited from at least 5 doses, the VE was at 80% when the last dose dated from less than 6 years earlier. DISCUSSION/CONCLUSION: The attack rate observed in our study was similar to those normally seen during epidemics occurring within a community. Vaccine efficacy declined depending on the time lapse since the last vaccination. Since April 2008, the Public Health Authorities have planned to provide pertussis booster vaccinations for children aged 16-18 who missed those for 11-13-year-old, and for adults aged 26-27 and those who have not been vaccinated for more than 10 years.

Protein kinase A and protein kinase C(alpha)/PPP1CC2 play opposing roles in the regulation of phosphatidylinositol 3-kinase activation in bovine sperm.

In order to acquire fertilization competence, spermatozoa have to undergo biochemical changes in the female reproductive tract, known as capacitation. Signaling pathways that take place during the capacitation process are much investigated issue. However, the role and regulation of phosphatidylinositol 3-kinase (PI3K) in this process are still not clear. Previously, we reported that short-time activation of protein kinase A (PRKA, PKA) leads to PI3K activation and protein kinase C(alpha)(PRKCA, PKC(alpha)) inhibition. In the present study, we found that during the capacitation PI3K phosphorylation/activation increases. PI3K activation was PRKA dependent, and down-regulated by PRKCA. PRKCA is found to be highly active at the beginning of the capacitation, conditions in which PI3K is not active. Moreover, inhibition of PRKCA causes significant activation of PI3K. Similar activation of PI3K is seen when the phosphatase PPP1 is blocked suggesting that PPP1 regulates PI3K activity. We found that during the capacitation PRKCA and PPP1CC2 (PP1gamma2) form a complex, and the two enzymes were degraded during the capacitation, suggesting that this degradation enables the activation of PI3K. This degradation is mediated by PRKA, indicating that in addition to the direct activation of PI3K by PRKA, this kinase can enhance PI3K phosphorylation indirectly by enhancing the degradation and inactivation of PRKCA and PPP1CC2.

[Pertussis surveillance in French military forces in 2007]. / Surveillance épidémiologique de la coqueluche dans les armées françaises en 2007.

OBJECTIVES: Pertussis surveillance in the French general population was stopped in 1986. Pertussis was added to the list of illnesses surveyed by the military epidemiological surveillance network because of outbreaks having occurred among French servicepersons and in military high schools. This study had for aim to report the results of the first year of surveillance. DESIGN: Pertussis declaration criteria were those recommended in 2006 by the French council for public hygiene. The data concerning active military servicepersons was collected by physicians of all military medical units. An anonymous declaration form was used for data collection. RESULTS: In 2007, 66 cases of pertussis were reported in the military forces, 10 of which were excluded after a negative biological test. The classification of the 56 included cases was: 46% biologically confirmed cases, 20% clinically confirmed cases, 14% suspected cases, and 6% epidemiologically confirmed cases. The incidence density rate was 16.3 cases for 100,000 servicepersons-years. Age under 20 was associated with a 4.6 fold higher risk to develop pertussis. CONCLUSIONS: The high incidence rate observed in individuals under 20 years of age could reflect a shift of pertussis reservoir to young adults, as observed in industrialized countries after generalization of vaccination programs. However, several years of surveillance will be needed to confirm this hypothesis. Meanwhile, the military epidemiological network could constitute an important surveillance marker of pertussis among adults in France.

Community-focused greywater management in two informal settlements in South Africa.

South Africa is struggling to provide services to the millions of poor people migrating to the major centres and living in informal settlements (shanty towns). Whilst the local authorities are generally able to provide potable water from the municipal network to communal taps scattered around the settlements, there is usually inadequate provision of sanitation and little or no provision for the drainage of either stormwater or greywater. This paper describes an investigation into ways of engaging with community structures in the settlements with a view to encouraging "self-help" solutions to greywater management requiring minimal capital investment as an interim "crisis" solution until such time that local and national government is able to provide formal services to everyone. The work was carried out in three settlements encompassing a range of different conditions. Only two are described here. It has become clear that the management of greywater has a low priority amongst the residents of informal settlements. The lack of effective political structures and the breakdown in communication with Ward Councillors and local government officials have contributed to the lack of progress. As the project progressed it became evident that greywater cannot be considered separately from stormwater, sanitation and refuse removal.

[Effectiveness of triennial anti-influenza vaccination in French military during the 2003-2004 influenza season]. / Evaluation de l'efficacité clinique de la vaccination antigrippale triennale dans les armées (saison 2003-2004).

BACKGROUND: Influenza may rapidly disseminate within populations living in confined settings, causing considerable morbidity and disrupting daily activities. The French military health-care system set up since 1994 a prevention strategy based on triennial anti-influenza vaccination. The aim of this study was to evaluate the effectiveness of this strategy during the 2003-2004 influenza season. METHODS: We conducted a matched case-control study from 10/01/2003 through 3/31/2004. Cases were laboratory-confirmed influenza cases. The controls were not to have presented influenza during all the period of study. Controls were matched to cases by sex, army unit and age. Subgroups were categorized into four groups by vaccination regimen [0-1 year], [1-2 years], [2-3 years], [3 years and more or unvaccinated]. RESULTS: One hundred and eighteen cases and 435 controls were included. The proportion of correctly vaccinated subjects (

Differences in biomarkers of type II collagen in atrophic and hypertrophic osteoarthritis of the hip: implications for the differing pathobiologies.

BACKGROUND: Cartilage destruction in osteoarthritis (OA) involves the excessive degradation and increased synthesis of cartilage matrix macromolecules including type II collagen (CII) and proteoglycans. The lack of osteophytes (atrophic form of OA) has been shown to be a disease severity factor in hip OA. Since osteophyte formation involves endochondral ossification and a cartilage intermediate, atrophic OA may also exhibit differences in cartilage turnover compared to hypertrophic OA. Cartilage serum biomarkers may offer an opportunity to identify such differences in patients. AIM: To determine whether serum levels of cartilage biomarkers can distinguish between the presence and absence of osteophyte formation in patients with atrophic and hypertrophic hip OA. PATIENTS AND METHODS: Fifty-six patients (mean age/standard deviation (SD): 62/11; mean body mass index (BMI)/SD: 27/11) with symptomatic hip OA (American College of Rheumatology criteria; mean Lequesne index/SD: 8.3/4) were classified as having an atrophic or hypertrophic form of OA, according to the absence or presence, respectively, of any osteophyte on a standard radiograph of the pelvis. Minimum joint space width (minJSW) and angles of dysplasia [centre-edge (CE) and head-neck-shaft (HNS)] were determined by computerized measurements. The following serum markers were used which are commercial kits from Ibex Diagnostics (Montreal, QC): proteoglycan aggrecans turnover: CS 846; CII synthesis: C-propeptide (CPII), cleavage by collagenase of type II (C2C) and type I and II (C1,2C) collagens. STATISTICS: Patients with atrophic and hypertrophic OA were compared for each variable and step to step logistic regression was used to determine the effect of variables on the belonging to each group. Correlations were examined using linear regression or Spearman test. RESULTS: CPII serum levels were significantly lower in the atrophic OA patients (77.3 vs 117.4 ng/mL). There were no significant differences between groups for C2C, C1,2C and CS 846 . CPII and C2C concentrations were highly correlated in hypertrophic OA (P=0.002) but not in atrophic OA (P=0.8). CONCLUSION: Atrophic hip OA is characterized by reduced synthetic activity involving type II collagen synthesis. This could account in part for the absence of osteophyte formation. The highly significant correlation between CPII and C2C in hypertrophic but not in atrophic OA suggests that the physiological coupling between CII formation and degradation may be lost in atrophic OA. These differences may therefore help explain the absence of osteophyte in atrophic OA and its association with more rapid disease progression.

[Impact and forecasting of hepatitis A immunization in French armed forces, 1990-2004]. / Impact et modélisation des effets attendus de la stratégie de vaccination contre les hépatites A chez les militaires français, 1990-2004.

BACKGROUND: Hepatitis A is a public health problem specially for migrants or travellers from industrialized countries with a low hepatitis A endemic level. French armed forces adopted an immunization strategy which first targeted overseas forces and subsequently was extended to all armed forces. In this work we studied the impact of this policy. METHODS: Epidemiological surveillance data from 1990 to 2004 was analyzed by Poisson regression and exponential models of decrease used to forecast future rates. RESULTS: From the 826 cases of hepatitis A reported during the study period, 266 (32.2%) occurred in overseas forces and 560 (67.8%) in forces stationed in France. Three periods could be identified in the decline of annual incidence: before 1994, with an average rate of 23.2 per 100,000; from 1994 to 1998: 10.2; and after 1998: 1.2 for all French armed forces. For overseas armed forces, the average rate was 117 per 100,000 before 1994 and 17.1 from 1994 to 1998 (p<0.001). For armed forces stationed in France, the average rate was 12.2 per 100,000 before 1998 and 0.9 after (p<0.001). For overseas armed forces, models clearly described the declining incidence subsequent to targeted immunization in 1995 and for armed forces stationed in France, the decline with generalized immunization starting in 1998. DISCUSSION: The impact of immunization against hepatitis A virus was significant both in an overseas population and in a population staying in France where the risk level can be considered low due to the low endemic rate in France. These results suggest that immunization should be proposed not only for travellers but also for the general population based on real knowledge of the situation and cost-effectiveness analyses.

[Outbreak of cutaneous leishmaniasis in military population coming back from French Guiana]. / Epidémie de leishmaniose cutanée chez des militaires de retour de mission en Guyane.

BACKGROUND: An outbreak of cutaneous leishmaniasis occurred among 71 soldiers who had participated in various missions during a 4-month's period in French Guiana. The aims of this study were (i) to describe outbreak and (ii) to determine risk factors of cutaneous leishmaniasis. METHODS: All patients were hospitalised. Cutaneous lesions were biopsied and cultured for species identification. Individual information was collected by a physician or a nurse, using on a standardised, anonymous chart. Data were processed with EpiInfo 6.04 and SAS. RESULTS: Mean age of the 71 soldiers was about 25.9 years (19-37 years). Twelve soldiers presented 56 lesions due to Leishmania (Viannia) guyanensis (attack rate = 16.9 for 100). Among 56 lesions, 13 lesions were localized on the trunk, usually an unexposed body area. Logistic regression highlighted military exercises in the forest during a high risk period of leishmaniasis transmission (OR = 11.2; p < 0.01), and the young age (OR = 1.33; p = 0.04). Vector control measures were not statistically significant. CONCLUSION: Military authorities should restrict deep forest activities during periods of high risk transmission. Vector control measures are essential. Officers should motivate their soldiers and supervise vector control measures. As ecotourism is developing, tourists as well as workers staying in deep forest must be informed of the risk and about vector control measures.

In vitro activity of iron-binding compounds against Senegalese isolates of Plasmodium falciparum.

OBJECTIVES: The in vitro activities of FR160, a synthetic catecholate siderophore, and two iron-binding agents, desferrioxamine and doxycycline, were evaluated against Plasmodium falciparum isolates. Correlations between these compounds and standard antimalarial drugs (chloroquine, quinine, amodiaquine, pyronaridine, artemether, artesunate, atovaquone, cycloguanil and pyrimethamine) were assessed to determine any degree of cross-resistance. METHODS: Between October 1997 and February 1998, and September and November 1998, 189 P. falciparum isolates were obtained in Dielmo and Ndiop (Dakar). Their susceptibilities were assessed using an isotopic, microwell format, drug susceptibility test. RESULTS: The 137 inhibitory concentrations (IC(50)) values of FR160 ranged from 0.1 to 10 microM and the geometric mean IC(50) was 1.48 microM (95% CI = 1.29-1.68 microM). The geometric mean IC(50) of doxycycline for 121 isolates was 18.9 microM (95% CI = 16.8-21.3 microM) and that of desferrioxamine for 73 isolates was 20.7 microM (95% CI = 17.3-24.8 microM). FR160 was significantly less active against the chloroquine-resistant isolates (P < 0.0001). The mean IC(50)s of doxycycline were significantly higher for the chloroquine-susceptible isolates than for the resistant parasites (P = 0.0447). There was a weak correlation between the responses to FR160, desferrioxamine or doxycycline and those to the other antimalarial compounds (r(2) < 0.22). CONCLUSIONS: The activities of FR160 and desferrioxamine, determined for P. falciparum clones, were confirmed against 137 isolates. The coefficients of determination between the responses to FR160, doxycycline or desferrioxamine and those to all the antimalarial drugs tested are too weak to suggest cross-resistance. FR160 could be a rationale partner to use in combination with doxycycline.

Menin molecular interactions: insights into normal functions and tumorigenesis.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease predisposed by heterozygous germline mutations in the MEN1 tumor suppressor gene. Biallelic loss of MEN1 resulting from small mutation and/or loss of heterozygosity occurs in a large tissue spectrum of MEN1 tumors or non-hereditary tumors. Mouse models of MEN1 underexpression or overexpression have also supported the tumor-suppressor effect of the MEN1 gene. Menin, the 610-amino-acid protein encoded by MEN1, is expressed ubiquitously and found predominantly in the nucleus. Sequence analyses do not reveal motifs of known function other than two nuclear localization sequences. Menin has been found to partner in vitro with a variety of proteins that comprise transcription factors, DNA processing factors, DNA repair proteins, and cytoskeletal proteins. The diverse functions of menin interactors suggest roles for menin in multiple biological pathways. Inactivation of menin switches its JunD partner from a downstream action of growth suppression to growth promotion. This is a plausible mechanism for menin tumorigenesis.