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Summary: Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022–July 2023). The first phase involved a survey to MASCC-MSG members (January 2022–May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023–May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.

Abstract Between 2014 and 2016, Switzerland’s access to some of the EU funding was limited after a referendum against mass immigration was accepted and the country refused to sign the free movement accord to the EU’s newest member, Croatia. It is well documented that Switzerland has suffered from a drop in participation, funding and a decrease in consortium lead positions. However, there is no account of the consequences on institutional level. We therefore aimed at describing the immediate- and longer-term impact of the partial association status to the Swiss Tropical and Public Health Institute (Swiss TPH) and to identify key strategies for minimizing institutional damage during a limited access period to a key regional funding source. A quantitative analysis of the institute’s grants database, from 2007 to 2019, did not show any clear trends related to the partial association status of Switzerland for funding and projects awarded. The qualitative outcomes changed along the timeline assessed; whereas in 2014 a range of negative effects were stated by Swiss TPH researchers, a survey conducted in 2019 with Swiss TPH applicants and project partners to Horizon 2020, revealed that most project leaders felt that the partial association did neither affect their external partners’ willingness to collaborate nor Swiss TPH’s role in the proposal or consortium. On the other hand, the institutional strategic goal of taking on consortia leads was delayed by several years as a direct consequence of the partial association. Also, the exclusion from European research networks and the lack of consultation of expertise by the European partner institutions was widely seen as damaging. A policy of favouring long-term partnerships over ad-hoc collaborations, along with constant and trustful communication, as immediate mitigation measure, helped averting some of the reputational and access damage. Moreover, the Swiss TPH business model based on a three-way strategy of research, education and services has proven highly viable allowing to build a large pool of potential funding sources internationally, resulting in relative resilience in terms of income lost.

Between August 2012 and April 2013 the Career Development Fellowship programme of the Special Programme for Research and Training in Tropical Diseases (World Health Organization) underwent an external evaluation to assess its past performance and determine recommendations for future programme development and continuous performance improvement. The programme provides a year-long training experience for qualified researchers from low and middle income countries at pharmaceutical companies or product development partnerships. Independent evaluators from the Swiss Tropical and Public Health Institute and the Barcelona Institute for Global Health used a results-based methodology to review the programme. Data were gathered through document review, surveys, and interviews with a range of programme participants. The final evaluation report found the Career Development Fellowship to be relevant to organizers' and programme objectives, efficient in its operations, and effective in its training scheme, which was found to address needs and gaps for both fellows and their home institutions. Evaluators found that the programme has the potential for impact and sustainability beyond the programme period, especially with the successful reintegration of fellows into their home institutions, through which newly-developed skills can be shared at the institutional level. Recommendations included the development of a scheme to support the re-integration of fellows into their home institutions post-fellowship and to seek partnerships to facilitate the scaling-up of the programme. The impact of the Professional Membership Scheme, an online professional development tool launched through the programme, beyond the scope of the Career Development Fellowship programme itself to other applications, has been identified as a positive unintended outcome. The results of this evaluation may be of interest for other efforts in the field of research capacity strengthening in LMICs or, generally, to other professional development schemes of a similar structure.

Background Childhood obesity is a major health concern. Obesity is due to an expansion of adipose tissue mass. This tissue produces pro􀁞inflarmnatory cytokines, such as interleukin􀁞6 (IL--6). IL􀁞6 is considered to be the chief stimulator of the production of highly sensitive C􀁞reactive protein (hsCRP) in the liver. Both molecules are responsible for the chronic low􀁞grade inflammatory state in obese individuals. Objective To assess a correlation between IL􀁞6 and hsCRP in obese adolescents. Methods This cross􀁞sectional study was conducted from March to June 2011 in Manado. Subjects were obese and normal body mass index (BMI) teens aged 13􀁞18 years. Serum glutamic oxaloacetic transaminase (SOOT) and serum glutamic pyruvic transaminase (SOPT) levels were measured to rule out liver impairment. IL􀁞6 and hsCRP levels were also measured. Data was analyzed by Pearson's correlation and linear regression to test for correlation between IL--6 and hsCRP levels. Results There was a strongly positive correlation between IL􀁞6 and hsCRP levels in obese adolescents (r=0.79 with P

BACKGROUND:Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans. Its exact mode of transmission is not known. Previous studies have identified demographic, socio-economic, health and hygiene as well as environment related risk factors. We investigated whether the same factors pertain in Suhum-Kraboa-Coaltar (SKC) and Akuapem South (AS) Districts in Ghana which previously were not endemic for BU. METHODS:We conducted a case control study. A case of BU was defined as any person aged 2 years or more who resided in study area (SKC or AS District) diagnosed according to the WHO clinical case definition for BU and matched with age- (+/-5 years), gender-, and community controls. A structured questionnaire on host, demographic, environmental, and behavioural factors was administered to participants. RESULTS:A total of 113 cases and 113 community controls were interviewed. Multivariate conditional logistic regression analysis identified presence of wetland in the neighborhood (OR=3.9, 95% CI=1.9-8.2), insect bites in water/mud (OR=5.7, 95% CI=2.5-13.1), use of adhesive when injured (OR=2.7, 95% CI=1.1-6.8), and washing in the Densu river (OR=2.3, 95% CI=1.1-4.96) as risk factors associated with BU. Rubbing an injured area with alcohol (OR=0.21, 95% CI=0.008-0.57) and wearing long sleeves for farming (OR=0.29, 95% CI=0.14-0.62) showed protection against BU. CONCLUSION:This study identified the presence of wetland, insect bites in water, use of adhesive when injured, and washing in the river as risk factors for BU; and covering limbs during farming as well as use of alcohol after insect bites as protective factors against BU in Ghana. Until paths of transmission are unraveled, control strategies in BU endemic areas should focus on these known risk factors.

Buruli ulcer (BU) is an emerging necrotizing disease of the skin and subcutaneous tissue caused by Mycobacterium ulcerans. While proximity to stagnant or slow flowing water bodies is a risk factor for acquiring BU, the epidemiology and mode of M. ulcerans transmission is poorly understood. Here we have used high-throughput DNA sequencing and comparisons of the genomes of seven M. ulcerans isolates that appeared monomorphic by existing typing methods. We identified a limited number of single nucleotide polymorphisms (SNPs) and developed a real-time PCR SNP typing method based on these differences. We then investigated clinical isolates of M. ulcerans on which we had detailed information concerning patient location and time of diagnosis. Within the Densu river basin of Ghana we observed dominance of one clonal complex and local clustering of some of the variants belonging to this complex. These results reveal focal transmission and demonstrate, that micro-epidemiological analyses by SNP typing has great potential to help us understand how M. ulcerans is transmitted.

Mycobacterium ulcerans is the causative agent of Buruli ulcer, the third most common mycobacterial disease after tuberculosis and leprosy. It is an emerging infectious disease that afflicts mainly children and youths in West Africa. Little is known about the evolution and transmission mode of M. ulcerans, partially due to the lack of known genetic polymorphisms among isolates, limiting the application of genetic epidemiology. To systematically profile single nucleotide polymorphisms (SNPs), we sequenced the genomes of three M. ulcerans strains using 454 and Solexa technologies. Comparison with the reference genome of the Ghanaian classical lineage isolate Agy99 revealed 26,564 SNPs in a Japanese strain representing the ancestral lineage. Only 173 SNPs were found when comparing Agy99 with two other Ghanaian isolates, which belong to the two other types previously distinguished in Ghana by variable number tandem repeat typing. We further analyzed a collection of Ghanaian strains using the SNPs discovered. With 68 SNP loci, we were able to differentiate 54 strains into 13 distinct SNP haplotypes. The average SNP nucleotide diversity was low (average 0.06-0.09 across 68 SNP loci), and 96% of the SNP locus pairs were in complete linkage disequilibrium. We estimated that the divergence of the M. ulcerans Ghanaian clade from the Japanese strain occurred 394 to 529 thousand years ago. The Ghanaian subtypes diverged about 1000 to 3000 years ago, or even much more recently, because we found evidence that they evolved significantly faster than average. Our results offer significant insight into the evolution of M. ulcerans and provide a comprehensive report on genetic diversity within a highly clonal M. ulcerans population from a Buruli ulcer endemic region, which can facilitate further epidemiological studies of this pathogen through the development of high-resolution tools.

BACKGROUND: Based on large genomic sequence polymorphisms, several haplotypes belonging to two major lineages of the human pathogen Mycobacterium ulcerans could be distinguished among patient isolates from various geographic origins. However, the biological relevance of insertional/deletional diversity is not understood. METHODOLOGY: Using comparative genomics, we have investigated the genes located in regions of difference recently identified by DNA microarray based hybridisation analysis. The analysed regions of difference comprise approximately 7% of the entire M. ulcerans genome. PRINCIPAL FINDINGS: Several different mechanisms leading to loss of functional genes were identified, ranging from pseudogenization, caused by frame shift mutations or mobile genetic element interspersing, to large sequence polymorphisms. Four hot spot regions for genetic instability were unveiled. Altogether, 229 coding sequences were found to be differentially inactivated, constituting a repertoire of coding sequence variation in the rather monomorphic M. ulcerans. CONCLUSIONS/SIGNIFICANCE: The differential gene inactivation patterns associated with the M. ulcerans haplotypes identified candidate genes that may confer enhanced adaptation upon ablation of expression. A number of gene conversions confined to the classical lineage may contribute to particular virulence of this group comprising isolates from Africa and Australia. Identification of this spectrum of anti-virulence gene candidates expands our understanding of the pathogenicity and ecology of the emerging infectious disease Buruli ulcer.

Elucidation of the transmission, epidemiology, and evolution of Mycobacterium ulcerans, the causative agent of Buruli ulcer, is hampered by the striking lack of genetic diversity of this emerging pathogen. However, by using a prototype plasmid-based microarray that covered 10% of the genome, we found multiple genomic DNA deletions among 30 M. ulcerans clinical isolates of diverse geographic origins. Many of the changes appear to have been mediated by insertion sequence (IS) elements IS2404 and IS2606, which have high copy numbers. Classification of the deleted genes according to their biological functions supports the hypothesis that M. ulcerans has recently evolved from the generalist environmental M. marinum to become a niche-adapted specialist. The substantial genomic diversity, along with a prototype microarray that covered a small portion of the genome, suggests that a genome-wide microarray will make available a genetic fingerprinting method with the high resolution required for microepidemiologic studies.