Leprosy in wild chimpanzees.

Humans are considered as the main host for Mycobacterium leprae1, the aetiological agent of leprosy, but spillover has occurred to other mammals that are now maintenance hosts, such as nine-banded armadillos and red squirrels2,3. Although naturally acquired leprosy has also been described in captive nonhuman primates4-7, the exact origins of infection remain unclear. Here we describe leprosy-like lesions in two wild populations of western chimpanzees (Pan troglodytes verus) in Cantanhez National Park, Guinea-Bissau and Taï National Park, Côte d'Ivoire, West Africa. Longitudinal monitoring of both populations revealed the progression of disease symptoms compatible with advanced leprosy. Screening of faecal and necropsy samples confirmed the presence of M. leprae as the causative agent at each site and phylogenomic comparisons with other strains from humans and other animals show that the chimpanzee strains belong to different and rare genotypes (4N/O and 2F). These findings suggest that M. leprae may be circulating in more wild animals than suspected, either as a result of exposure to humans or other unknown environmental sources.

National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany - study protocol of a mixed-methods project.

BACKGROUND: In the SARS-CoV-2 pandemic, general and specialist Palliative Care (PC) plays an essential role in health care, contributing to symptom control, psycho-social support, and providing support in complex decision making. Numbers of COVID-19 related deaths have recently increased demanding more palliative care input. Also, the pandemic impacts on palliative care for non-COVID-19 patients. Strategies on the care for seriously ill and dying people in pandemic times are lacking. Therefore, the program 'Palliative care in Pandemics' (PallPan) aims to develop and consent a national pandemic plan for the care of seriously ill and dying adults and their informal carers in pandemics including (a) guidance for generalist and specialist palliative care of patients with and without SARS-CoV-2 infections on the micro, meso and macro level, (b) collection and development of information material for an online platform, and (c) identification of variables and research questions on palliative care in pandemics for the national pandemic cohort network (NAPKON). METHODS: Mixed-methods project including ten work packages conducting (online) surveys and qualitative interviews to explore and describe i) experiences and burden of patients (with/without SARS-CoV-2 infection) and their relatives, ii) experiences, challenges and potential solutions of health care professionals, stakeholders and decision makers during the SARS-CoV-2 pandemic. The work package results inform the development of a consensus-based guidance. In addition, best practice examples and relevant literature will be collected and variables for data collection identified. DISCUSSION: For a future "pandemic preparedness" national and international recommendations and concepts for the care of severely ill and dying people are necessary considering both generalist and specialist palliative care in the home care and inpatient setting.

Question prompts to empower cancer patients: results of a randomized controlled trial.

OBJECTIVE: In addition to question prompts for information transfer, we also used prompts to facilitate the expression of emotions. Our aim was to investigate how a question prompt list (QPL) is accepted by patients and whether it enhances interactional empowerment of the patients in the consultation with the radio-oncological treatment team before the beginning of radiotherapy. METHODOLOGY: Adult cancer patients before the beginning of radiotherapy were randomly assigned to the intervention group (IG) or control group (CG). The patients in the IG received a QPL with predefined subsets and subject areas. After the physician's consultation, both groups completed a self-developed, content validated questionnaire on interactional empowerment. The IG evaluated the QPL using a self-developed instrument. RESULT: A total of 279 adult cancer patients participated in the study (IG n = 139/CG n = 140). The participants of the IG reported a significantly higher interactional empowerment compared with those of the CG (t(277) = - 2.71, p = .007, 95% CI [- 1.61, - 0.26], d = 0.29). 60.4% of the IG agreed "rather" or "very" that they used the QPL in consultation with the medical team. CONCLUSION: The QPL used in the consultation improved the self-assessed competence for interaction with the medical team and strengthened the interactional empowerment. The QPL was well accepted by the patients and is to be introduced into a routine as a practicable and simple instrument in the future. The support of patients in addressing concerns and fears is an important innovation.

[Needs and burdens of palliative care patients with advanced and/or metastatic head and neck tumors]. / Bedürfnisse und Belastungen von palliativmedizinisch mitbetreuten Patienten mit fortgeschrittenen und/oder metastasierten Kopf-Hals-Tumoren.

BACKGROUND: New therapeutic modalities enable good treatment options for patients with advanced and metastatic head and neck cancer. In this context, discussions about the end of life, advance care planning, and palliative concepts are often eclipsed. OBJECTIVE: Analysis of symptom burden and advance directives of palliatively comanaged inpatients using a palliative care self-assessment questionnaire. Based on the Earle quality indicator (QI), the integration of specialized palliative care in deceased inpatients was examined. PATIENTS AND METHODS: Retrospective analysis of head and neck cancer patients cotreated by the palliative care service. Patients were surveyed using the Integrated Palliative Care Outcome Scale (IPOS) questionnaire. RESULTS: The most frequent physical symptoms were weakness (77%), loss of appetite (65%), and poor mobility (65%). Pain was reported by 41% of patients. The most frequent emotional and psychosocial burdens were depression (97%) and worries about illness or treatment (94%), lack of ability to share feelings (77%), lack of information (85%), and organizational problems (77%). In 23% of patients, advanced directives were available. The Earle QI was not achieved. DISCUSSION: Patients report a high degree of symptoms and stress, most often in emotional areas and in terms of communicative and practical needs. This may reflect a need to talk about wishes and expectations concerning the end of life. Palliative care services should aim to address psychosocial needs in particular.

[Chronic pain and artificial diseases]. / Chronischer Schmerz und artifizielle Erkrankungen.

A 34-year-old woman presented with a complex pain disorder and a previous diagnosis of the rare Gitelman syndrome but with a negative genetic test. The patient was admitted to a routine ward for treatment of the pain but was transferred to the intensive care unit after suffering severe hypokalemia and a narcoleptic attack. In the period of intensive care all blood parameters were stable but on release to the normal ward severe hypokalemia immediately reoccurred. With consent the patient's belongings were inspected and many diuretics and laxatives were found. The patient admitted to uncontrolled self-medication so that the diagnosis of Gitelman syndrome also appeared to be an artificial disorder.

Human xylosyltransferase-I - a new marker for myofibroblast differentiation in skin fibrosis.

Skin fibrosis is a severe type of fibrotic disorder emerging in terms of hypertrophic scars or systemic sclerosis. Key event of fibrogenesis is the transition of fibroblasts to matrix-producing myofibroblasts. In the presence of fibrotic triggers, for instance secretion of profibrotic growth factors like transforming growth factor-ß1 (TGF-ß1) or mechanical strain, myofibroblasts persist. Current research focuses on discovering innovative myofibroblast biomarkers which are regulated in fibrotic development and accessible for antifibrotic inhibition. Here, we consider the suitability of xylosyltransferase-I (XT-I) as a myofibroblast biomarker in skin fibrosis. XT-I catalyzes the initial step of glycosaminoglycan biosynthesis. Its increase in enzymatic activity is known to refer only to manifested diseases which are characterized by an abnormal rate of proteoglycan biosynthesis. In this study, treatment of normal human dermal fibroblasts (NHDF) with TGF-ß1 was followed by increased relative XYLT1 mRNA expression. Remarkably, this upregulation was strongly dependent on myofibroblast content, increasing during fibrogenesis. Moreover, XT activity increased time-dependently in response to progressive myofibroblast transformation. XYLT1 expression was inhibited by TGF-ß receptor I (ALK5) inhibitor SB431542. In contrast, XYLT2 expression was only marginally affected by TGF-ß1 as well as ALK5 inhibition. Our results strengthen the significance of XT expression and activity in fibrotic remodeling. Therefore, we propose XT activity, in addition to α-SMA expression, as a new biomarker for myofibroblast differentiation and fibrotic development. Further studies are now needed to evaluate the option to control and inhibit fibrotic remodeling by interfering with XT expression.

[General palliative care during the pandemic]. / Allgemeine Palliativversorgung in Pandemiezeiten.

BACKGROUND: The German healthcare system is facing unprecedented challenges due to the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Palliative care for critically ill patients and their families was also severely compromised, especially during the first wave of the pandemic, in both inpatient and outpatient settings. MATERIALS AND METHODS: The paper is based on our experience in routine inpatient palliative care and partial results of a study conducted as part of the collaborative project "National Strategy for Palliative Care in Pandemic Times (PallPan)". Based on our experience from the inpatient care of patients suffering from severe or life-limiting disease, best-practice examples for improving or maintaining care in the on-going pandemic are described. RESULTS: Restrictive visitor regulations, communication barriers and insufficient possibilities to accompany dying patients or their grieving relatives continue to pose major challenges in general and specialized inpatient palliative care. In order to maintain high-quality palliative care, it is necessary to create structures that enable targeted therapy discussions and end-of-life care in the presence of relatives. Therefore, innovative communication methods like video calls or individualized exceptions from visitor restrictions are needed. CONCLUSIONS: Adequate care for seriously ill and dying patients and their relatives must be guaranteed during the pandemic. Individual arrangements should be arranged and implemented. If available, earlier involvement of specialized palliative care teams can be beneficial.

The paediatric participation scale measuring participation restrictions among former Buruli Ulcer patients under the age of 15 in Ghana and Benin: Development and first validation results.

BACKGROUND: Buruli Ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. Former BU patients may experience participation restrictions due to physical limitations, stigmatization and other social factors. A scale that measures participation restrictions among children, who represent almost half of the affected population, has not been developed yet. Here, we present the development of a scale that measures participation restrictions in former BU paediatric patients, the psychometric properties of this scale and the scales' results. METHODS: Items were selected and a scale was developed based on interviews with health care workers and former BU patients in and around the BU treatment centre in Lalo, Benin. Construct validity was tested using six a priori formulated hypotheses. Former BU patients under 15 years of age who received treatment in one of the BU treatment centres in Ghana and Benin between 2007-2012 were interviewed. RESULTS: A feasible 16-item scale that measures the concept of participation among children under 15 years of age was developed. In total, 109 (Ghana) and 90 (Benin) former BU patients were interviewed between 2012-2017. Five construct validity hypotheses were confirmed of which 2 hypotheses related to associations with existing questionnaires were statistically significant (p<0.05). In Ghana 77% of the former patients had a Paediatric Participation (PP) scale score of 0 compared to 22% in Benin. More severe lesions related to BU were seen in Benin. Most of the reported participation problems were related to sports, mainly in playing games with others, going to the playfield and doing sports at school. CONCLUSION: The preliminary results of the PP-scale validation are promising but further validation is needed. The developed PP-scale may be valid for use in patients with more severe BU lesions. This is the first research to confirm that former BU patients under 15-year face participation restrictions in important aspects of their lives.

Setting up a national reference laboratory for Buruli ulcer: the case of Benin.

OBJECTIVE: To report the experience of Benin, where Buruli ulcer (BU) is endemic, in the implementation of diagnostic laboratory services. METHODS AND RESULTS: There has been a gradual introduction of biologic diagnostic activities for BU comprising (1) training of a laboratory technician in a highly experienced reference laboratory; (2) acquiring indispensable laboratory start-up materials; (3) progressive development of diagnostic laboratory activities; (4) regular external quality assessment with an experienced reference laboratory and (5) decentralization of activities to various clinical diagnostic and treatment centres for BU in Benin. CONCLUSION: Setting up a reference laboratory for BU is a continuous process, which necessitates motivated personnel and the cooperation of an experienced external reference laboratory.

Delayed versus standard assessment for excision surgery in patients with Buruli ulcer in Benin: a randomised controlled trial.

BACKGROUND: Surgical intervention was once the mainstay of treatment for Buruli ulcer disease, a neglected tropical disease caused by Mycobacterium ulcerans. Since the introduction of streptomycin and rifampicin for 8 weeks as standard care, surgery has persisted as an adjunct therapy, but its role is uncertain. We investigated the effect of delaying the decision to operate to 14 weeks on rates of healing without surgery. METHODS: In this randomised controlled trial, we enrolled patients aged 3 years or older with confirmed disease at one hospital in Lalo, Benin. Patients were randomly assigned (1:1) to groups assessing the need for excision surgery 8 weeks (standard care) or 14 weeks after initiation of antimicrobial treatment. The primary endpoint was the number of patients healed without the need for surgery (not including skin grafting), assessed in all patients in follow-up at 50 weeks (or last observation for those healed for >10 weeks). A doctor masked to treatment assignment checked the indications for surgery according to predefined criteria. This study is registered with ClinicalTrials.gov, number NCT01432925. FINDINGS: Between July 1, 2011, and Jan 15, 2015, 119 patients were enrolled, with two patients per group lost to follow-up. 55 (96%) of 57 participants in the delayed-decision group and 52 (90%) of 58 participants in the standard-care group had healed lesions 1 year after start of antimicrobial treatment (relative risk [RR] 1·08, 95% CI 0·97-1·19). 37 (67%) of 55 patients in the delayed-decision group had their lesions healed without surgical intervention, as did 25 (48%) of 52 in the standard-care group (RR 1·40, 95% CI 1·00-1·96). The time to heal and residual functional limitations did not differ between the two groups (median time to heal 21 weeks [IQR 10-27] in the delayed-decision group and 21 weeks [10-39] in the standard-care group; functional limitations in six [11%] of 57 and three [5%] of 58 patients; p=0·32). Postponing the decision to operate resulted in reduced median duration of hospitalisation (5 days [IQR 0-187] vs 131 days [0-224]; p=0·024) and wound care (153 days [IQR 56-224] vs 182 days [94-307]; p=0·036). INTERPRETATION: In our study, patients treated for Buruli ulcer benefited from delaying the decision to operate. Even large ulcers can heal with antibiotics alone, without delaying healing rate and without an increase in residual functional limitations. FUNDING: NWO-VENI grant 241500, BUG Foundation, and UBS OPTIMUS.

Amplified fragment length polymorphism, serotyping, and quinolone resistance of Campylobacter jejuni and Campylobacter coli strains from chicken-related samples and humans in Taiwan.

The high-resolution genotyping method of amplified fragment length polymorphism (AFLP) analysis was used to study the genetic relationships between Campylobacter jejuni isolates from chicken-related samples (n = 32) and humans (n = 27) as well as between Campylobacter coli isolates from chicken-related samples (n = 27) and humans (n = 5). These isolates were collected between 1994 and 2003 in Taiwan. All C. jejuni and C. coli isolates showed highly heterogeneous fingerprints. C. jejuni isolates were separated in two distinct genetic clusters (A and B) at 40% genetic similarity and 42 different AFLP types at 90% similarity. However, three clusters at 40% genetic similarity and 33 different AFLP types at 90% similarity were observed in C. coli isolates. These results showed that AFLP analysis could be used to identify individual isolates of two Campylobacter species. Among C. jejuni isolates, the predominant AFLP type 1 was observed in five (7.9%) isolates, and types 5 and 12 in four (6.3%) isolates each. Cluster B consisted of 10 isolates, while the majority of isolates (n = 53) belonged to cluster A. In some AFLP types (1, 5, 12, 14 and 31), AFLP fingerprints of chicken-related isolates were closely related genetically to those of isolates from humans with gastroenteritis. The predominant serotypes in C. jejuni isolates were B:2 and Y:37. All isolates belonging to serotype O:19 grouped into one single AFLP type. Some chicken samples yielded multiple isolates of Campylobacter harboring simultaneously quinolone-resistant and quinolone-sensitive isolates attributed to the same species, or harboring C. jejuni and C. coli that have the characteristics of quinolone resistance.

Detection of late epilepsy by the texture analysis of MR brain images in the lithium-pilocarpine rat model.

The aim of the study was to detect by texture analysis non easily visible anomalies of magnetic resonance (MR) images of piriform and entorhinal cortices relevant to the lithium-pilocarpine (Li-Pilo) model of temporal lobe epilepsy in rats. Status epilepticus was induced by Li-Pilo in twenty male rats 21 day-old. T(2)-weighted MR images of their brain, were obtained before injection of Li-Pilo and one day after status epilepticus. An hyperintense signal was found in the piriform and entorhinal cortices of six rats, which developed chronic epilepsy after a latent period of one to three months. Among the 14 other rats which displayed images similar to those obtained before injection, four remained healthy but 10 rats developed late epileptic symptoms, raising the problem of hidden cortical damage which may be too subtle to be detected by classic MRI examination. A numeric treatment of digital images was then undertaken by texture analysis, to derive image information from a purely computational point of view. The combined texture and discriminant analyses based on pixels pattern anomalies, selected 3 texture parameters derived from co-occurrence matrix which characterized structural abnormalities relevant to the hyperintense signal, not only in the modified images of 6 rats but also in images of 10 rats with apparently non modified images. These three texture's parameters allowed to classify the twenty rats of our experiment as follows: sixteen epileptic rats were effectively classified with cortical lesions, two non epileptic were correctly classified with healthy cortex, but two healthy rats were not correctly classified. This misclassification is discussed on the basis of the time dependence of the onset of seizure in the Li-Pilo model. These promising results suggest to apply this method to MRI examinations for an improvement of the early diagnostic of human epilepsy.

Automatic learning strategies and their application to electrophoresis analysis.

Automatic learning plays an important role in image analysis and pattern recognition. A taxonomy of automatic learning strategies is presented; this categorization is based on the amount of inferences the learning element must perform to bridge the gap between environmental and system knowledge representation level. Four main categories are identified and described: rote learning, learning by deduction, learning by induction, and learning by analogy. An application of learning by induction to medical image analysis is then exposed. It consists in the classification of two-dimensional gel electrophoretograms into meaningful distinct classes, as well in their conceptual description.

Clinical considerations on Buruli ulcer employing two molecular tests for the detection of Mycobacterium ulcerans in 100 skin biopsies.

OBJECTIVES: Buruli ulcer (BU) is an infected cutaneous lesion, the etiological agent of which is Mycobacterium ulcerans. Diagnosis is confirmed by the identification of acid-fast bacilli and culture. In clinically suspicious forms with negative bacteriological or Ziehl-Neelsen (ZN) findings, molecular tests are used. This study compared the concordance of nested polymerase chain reaction (PCR) (targeting IS2404) and PCR (targeting IS2606) in different clinical situations. METHODS: A total of 57 samples were sourced from 39 BU patients. Control samples (n = 43) were obtained from non-BU ulcers in 38 patients. Samples were divided into two pieces and submitted to, respectively, histological examination and ZN staining, and PCR. Subsamples submitted to PCR were divided and submitted to nested PCR IS2404 and PCR IS2606, respectively. RESULTS: Of the 57 BU biopsies, positive results were obtained by nested PCR in 18 (31.6%) and by IS2606 PCR in 37 (64.9%) cases. Sequencing of the positive samples confirmed the specificity of amplicons in all nested PCR samples and in 26 of 37 (70.2%) samples positive to IS2606. Hence, nested PCR was more specific (100% vs. 93%) and less sensitive (32% vs. 46%) than IS2606 PCR. In the BU samples, nested PCR was negative in 15 instances, and IS2606 PCR was negative in 11 instances in which ZN histology had been positive (false negatives). Both PCRs were positive in six ZN-negative smears. CONCLUSIONS: We considered 57 samples from 39 BU patients in various clinical stages and at different times after the beginning of therapy. These provided positive results in 18 cases with IS2404 nested PCR and in 37 cases with PCR IS2606; only 26 of the latter remained positive subsequent to sequencing. Hence, even if IS2404 PCR is considered more specific, in subjects who appear to fail to respond to therapy, it is advisable to also carry out IS2606 PCR. A possible interpretation of the discordance between the two techniques due to unavoidable technical errors as well as to different sensitivity of the two tests at M. ulcerans DNA low concentration (i.e. in recent infection and in well-treated cases) is discussed.

Association of HIV infection and Mycobacterium ulcerans disease in Benin.

We investigated the association between Buruli ulcer and HIV by comparing the HIV-1/2 seroprevalence in a series of 426 Buruli ulcer patients and a sample of 613 residents of southern Benin. The overall HIV prevalence was 2.6% (11/426) among patients and 0.3% among controls (2/613), giving an odds ratio for the association between HIV and Buruli ulcer of 8.1 (95% confidence interval = 1.8-75; P = 0.003).

Environmental and health-related risk factors for Mycobacterium ulcerans disease (Buruli ulcer) in Benin.

We conducted a case-control study to investigate the association between Buruli ulcer (BU) and environmental- and health-related behaviors in southern Benin. Hospital BU cases (N = 324) and sex- and age-matched neighborhood controls (N = 1,173) answered a questionnaire. Regular use of soap for washing, treating injuries with soap or antibiotic powder, and frequent contact with flowing water appeared protective against BU.

Association between haemoglobin variants S and C and Mycobacterium ulcerans disease (Buruli ulcer): a case-control study in Benin.

Risk factors for Buruli ulcer (BU) are poorly understood. We conducted a case-control study in southern Benin to investigate the association between haemoglobin variants S or C and BU, and particularly the association between haemoglobinopathies HbSS/SC and BU osteomyelitis. We compared the haemoglobin genotype of 179 patients with BU and 44 with BU osteomyelitis to that of 242 community controls. We found no evidence of an increased risk of BU according to the presence of haemoglobin variants S and/or C [odds ratio adjusted for sex, age, region of residence and ethnicity: 1.24 (95% CI: 0.80-1.93), P = 0.34]. Haemoglobin variants S and C are unlikely to play a role in the BU burden. However, haemoglobinopathies HbSS/SC were more frequent among BU osteomyelitis patients than among controls (6.8% vs. 1.0%, Fisher's exact P-value = 0.045), which may suggest that those disorders facilitate growth of Mycobacterium ulcerans in the bone matrix.

Automatic classification of two-dimensional gel electrophoresis pictures by heuristic clustering analysis: a step toward machine learning.

The interpretation of two-dimensional gel electrophoresis (2-DGE) profiles can be facilitated by artificial intelligence and machine learning programs. We have incorporated into our 2-DGE computer analysis system (termed MELANIE-Medical Electrophoresis Analysis Interactive Expert system) a program which automatically classifies 2-DGE patterns using heuristic clustering analysis. This program is a step toward machine learning. In this publication, we describe the classification method and the preliminary results obtained with liver biopsy electrophoretograms. Heuristic clustering is also compared to other classification techniques.