Reducing fatigue in pediatric rheumatic conditions: a systematic review.

BACKGROUND: Although fatigue is a prevalent distressing symptom in children and adolescents with Pediatric Rheumatic Conditions (PRCs), intervention studies designed for reducing fatigue in PRCs are limited. AIM: To systematically review evidence regarding the efficacy of interventions intended to reduce fatigue in patients with PRCs. METHODS: Comprehensive electronic searches were performed in PubMed/ MEDLINE, Embase, Web of Science and Cinahl. The risk of bias was assessed using the 'Revised Cochrane risk-of-bias tool for randomized trials' and 'Quality Assessment Tool for Before-After Studies With No Control Group' for respectively studies with and without a control group. RESULTS: Ten out of 418 studies were included with a total of 240 participants (age range 5-23 years). Interventions included land-based and aquatic-based exercise therapy, prednisolone, vitamin-D and creatine supplementation, psychological therapy and a transition program into an adult rheumatology program. Fatigue was assessed with self-reported questionnaires in all included studies. Land-based exercise therapy was effective in one pre-post intervention study, whereas not effective in two randomized controlled trials. Aquatic-based exercise therapy was found more effective than land-based exercise therapy. Two placebo-controlled studies showed a significant positive effect in reducing subjective fatigue with prednisolone and vitamin-D. Creatine was not found effective. Cognitive therapy was effective in one pre-post intervention study, while one RCT did not show an effect in reducing fatigue. A transition program based on health education showed a small reducing effect, however, it was not clear if this was a significant effect. Six studies showed a high risk of bias, three studies a moderate risk, and one study had a low risk of bias. CONCLUSIONS: Insufficient evidence is provided to substantiate the efficacy of current interventions to reduce fatigue in PRCs. The low number of studies, non-comparable interventions, risk of bias, and inconclusive outcomes of the included studies denote future research should focus on intervention studies aimed at the treatment of fatigue in children and adolescents with PRCs. Identification of possible underlying biological and psychosocial mechanisms as possible treatment targets to reduce complaints of fatigue in children and adolescents with PRCs is warranted.

Reference values for cardiopulmonary exercise testing in healthy subjects - an updated systematic review.

Introduction: Reference values for cardiopulmonary exercise testing (CPET) parameters provide the comparative basis for answering important questions concerning the normalcy of exercise responses in patients, and significantly impacts the clinical decision-making process. Areas covered: The aim of this study was to provide an updated systematic review of the literature on reference values for CPET parameters in healthy subjects across the life span. A systematic search in MEDLINE, Embase, and PEDro databases were performed for articles describing reference values for CPET published between March 2014 and February 2019. Expert opinion: Compared to the review published in 2014, more data have been published in the last five years compared to the 35 years before. However, there is still a lot of progress to be made. Quality can be further improved by performing a power analysis, a good quality assurance of equipment and methodologies, and by validating the developed reference equation in an independent (sub)sample. Methodological quality of future studies can be further improved by measuring and reporting the level of physical activity, by reporting values for different racial groups within a cohort as well as by the exclusion of smokers in the sample studied. Normal reference ranges should be well defined in consensus statements.

Different action patterns of glucoamylases on branched gluco-oligosaccharides from amylopectin.

A bottleneck in enzymatic starch hydrolysis, like in biofuel industry, is relatively slow degradation of branched structures compared to linear ones. This research aimed to evaluate glucoamylases for their activity towards branched gluco-oligosaccharides. The activity of seven modified glucoamylases and two homologs was compared to that of a reference glucoamylase obtained from a commercial enzyme cocktail 'Distillase® SSF'. All enzymes were evaluated for their activity towards panose (glc(α1-6)glc(α1-4)glc), pullulan and a purified branched gluco-oligosaccharide with a degree of polymerisation of 5 (bDP5) identified as glc(α1-4)[glc(α1-4)glc(α1-6)]glc(α1-4)glc. The enzymes degraded bDP5 differently, which was mainly due to variation in their capability to cleave α-(1→6)-linked or the α-(1→4)-linked glucosyl residue at the non-reducing end of the branched glucosyl residue. By comparing the enzyme activity towards bDP5 with those towards panose and pullulan, it was suggested that the activity towards bDP5 could be estimated only when the activity towards both commercial substrates was evaluated.

Characterisation of branched gluco-oligosaccharides to study the mode-of-action of a glucoamylase from Hypocrea jecorina.

In the conversion of starch to fermentable glucose for bioethanol production, hydrolysis of amylopectin by α-amylases and glucoamylases is the slowest step. In this process, α-1,6-branched gluco-oligosaccharides accumulate and are slowly degraded. Glucoamylases that are able to degrade such branched oligosaccharides faster are economically beneficial. This research aimed at the isolation and characterisation of branched gluco-oligosaccharides produced from amylopectin digestion by α-amylase, to be used as substrates for comparing their degradation by glucoamylases. Branched gluco-oligosaccharides with a DP between five and twelve were purified using size exclusion chromatography. These structures were characterised after labelling with 2-aminobenzamide using UHPLC-MS(n) analysis. Further, the purified oligosaccharides were used to evaluate the mode-of-action of a glucoamylase from Hypocrea jecorina. The enzyme cleaves the α-1,4-linkage adjacent to the α-1,6-linkage at a lower rate than that of α-1,4-linkages in linear oligosaccharides. Hence, the branched gluco-oligosaccharides are a suitable substrate to evaluate glucoamylase activity on branched structures.

Reliability of Repeated Measurements on Post-Burn Scars with Corneometer CM 825(®).

BACKGROUND/PURPOSE: The water content in burn scars, the parameter of stratum corneum water holding capacity, is an important feature in evaluation of biophysical properties of scars. Nevertheless, quantifiying this parameter is a challenge. In this study, the reliability of repeated water content measurements with Corneometer CM825(®) on (burn) scars was investigated. METHODS: Intra-observer reliability, inter-observer reliability and day-by-day variability were examined on 30 scars by means of intra-class correlation coefficient (ICC) and within-subject coefficient of variation (WSCV). Bland-Altman plots with '95% limits of agreement' were constructed. RESULTS: Results revealed excellent ICC values (ICCintra  = 0.985; ICCinter  = 0.984) with relatively low WSCV (WSCVintra  = 6.3%; WSCVinter  = 10.6%) for respectively intra- and inter-observer reliability. However, the Bland-Altman plot showed that more than 5% of differences were expected to exceed 4 a.u., the limit of what has been defined as a clinically acceptable difference. Results for day-by-day variability showed good ICC value (ICCday-by-day  = 0.849) and higher WSCV (WSCVday-by-day  = 20.5%). CONCLUSION: The Corneometer CM825(®) is an objective and sensitive instrument for water content measurements. On the basis of our results, we concluded that the instrument can be used in clinical trials, but only under very strict conditions with standardized test protocol, preferably in combination with the evaluation of other physiological parameters.

Towards an individualized protocol for workload increments in cardiopulmonary exercise testing in children and adolescents with cystic fibrosis.

BACKGROUND: There is no single optimal exercise testing protocol for children and adolescents with cystic fibrosis (CF) that differs widely in age and disease status. The aim of this study was to develop a CF-specific, individualized approach to determine workload increments for a cycle ergometry testing protocol. METHODS: A total of 409 assessments consisting of maximal exercise data, anthropometric parameters, and lung function measures from 160 children and adolescents with CF were examined. 90% of the database was analyzed with backward linear regression with peak workload (W(peak)) as the dependent variable. Afterwards, we [1] used the remaining 10% of the database (model validation group) to validate the model's capacity to predict W(peak) and [2] validated the protocol's ability to provide a maximal effort within a 10±2 minute time frame in 14 adolescents with CF who were tested using this new protocol (protocol validation group). RESULTS: No significant differences were seen in W(peak) and predicted W(peak) in the model validation group or in the protocol validation group. Eight of 14 adolescents with CF in the protocol validation group performed a maximal effort, and seven of them terminated the test within the 10±2 minute time frame. Backward linear regression analysis resulted in the following equation: W(peak) (W)=-142.865+2.998×Age (years)-19.206×Sex (0=male; 1=female)+1.328×Height (cm)+23.362×FEV(1) (L) (R=.89; R(2)=.79; SEE=21). Bland-Altman analysis showed no systematic bias between the actual and predicted W(peak). CONCLUSION: We developed a CF-specific linear regression model to predict peak workload based on standard measures of anthropometry and FEV(1), which could be used to calculate individualized workload increments for a cycle ergometry testing protocol.

The oxygen uptake efficiency slope in children with congenital heart disease: construct and group validity.

OBJECTIVE: The oxygen uptake efficiency slope (OUES) has been proposed as an independent and objective alternative to the peak oxygen uptake (VO(2peak)), which does not require maximal exercise. The aim of this study was to investigate the construct and group validity of the OUES in children with congenital heart disease (CHD). METHODS: Thirty-one patients with CHD, of which 16 patients (mean age ± SD 11.2 ± 2.7 years) with a Fontan repair and 15 patients (mean age ± SD 13.2 ± 3.6 years) with surgical repair of tetralogy of Fallot (ToF) completed a symptom-limited cardiopulmonary exercise test. The OUES was calculated and normalized for body surface area at three different exercise intensities: (1) using 100% of the exercise data; (2) using the first 75% of the exercise data; and (3) using exercise data up to the ventilatory threshold (VT). Furthermore, peak oxygen uptake (VO(2peak)), VT, ventilatory efficiency (V(E)/VO(2)-slope), and ventilatory drive (V(E)/VCO(2)-slope) were calculated and compared with values of 46 healthy children (mean age ± SD 12.2 ± 2.4 years). RESULTS: In all three groups, the OUES values determined at the three different exercise intensities were not significantly different from each other. Moreover, the OUES was significantly reduced in the children with CHD, with significantly lower values in the Fontan patients compared to ToF. Strong correlations were found between the OUES and both the VO(2peak) and VT in Fontan and ToF patients. DISCUSSION: The OUES provides a valid measure of cardiopulmonary fitness in children with CHD, which is independent of exercise intensity and strongly correlated with VO(2peak) and VT (construct validity). Furthermore, the OUES is capable of differentiating between healthy children and children with CHD and between Fontan and ToF patients (group validity). Therefore, the OUES may be a valid, effort-independent parameter of cardiopulmonary fitness in children with CHD.

Cardiopulmonary exercise testing in congenital heart disease: equipment and test protocols.

Cardiopulmonary exercise testing (CPET) in paediatric cardiology differs in many aspects from the tests as performed in adult cardiology. Children's cardiovascular responses during exercise testing present different characteristics, particularly oxygen uptake, heart rate and blood pressure response, which are essential in interpreting haemodynamic data. Diseases that are associated with myocardial ischaemia are very rare in children. The main indications for CPET in children are evaluation of exercise capacity and the identification of exercise-induced arrhythmias. In this article we will review exercise equipment and test protocols for CPET in children with congenital heart disease. (Neth Heart J 2009;17:339-44.).

Cardiopulmonary exercise testing in congenital heart disease: (contra)indications and interpretation.

Cardiopulmonary exercise testing (CPET) in paediatric cardiology differs in many aspects from the tests performed in adult cardiology. Children's cardiovascular responses during exercise testing present different characteristics, particularly oxygen uptake, heart rate and blood pressure response, which are essential in interpreting haemodynamic data. Diseases that are associated with myocardial ischaemia are rare in children. The main indications for CPET in children are evaluation of exercise capacity and the identification of exercise-induced arrhythmias. In this article we will review the main indications for CPET in children with congenital heart disease, the contraindications for exercise testing and the indications for terminating an exercise test. Moreover, we will address the interpretation of gas exchange data from CPET in children with congenital heart disease. (Neth Heart J 2009;17:385-92.).

Prevention of glucocorticoid-induced osteoporosis.

Glucocorticoid-induced osteoporosis is the most common cause of secondary osteoporosis. The role of the Wnt signaling pathway in bone formation and the ratio of receptor activator for NF-kappaB ligand versus osteoprotegerin in bone resorption are exciting new insights. The absolute fracture risk helps both clinicians and patients to interpret the results of bone density measurement, which may have a positive influence on adherence to therapy. The bisphosphonates alendronate and risedronate are the first-line treatment in the prevention of glucocorticoid-induced osteoporosis, because both increase the bone mineral density of the spine and hips and reduce the vertebral fracture rate. Treatment with the anabolic agent parathyroid hormone (1 - 34) strongly stimulates bone turnover, and seems to be superior to treatment with alendronate. It might be attractive for glucocorticoid-treated patients with new vertebral fractures during treatment with bisphosphonates, and/or with severe fracture risk.

Exercise therapy in juvenile idiopathic arthritis: a Cochrane Review.

BACKGROUND: Exercise therapy is considered an important component of the treatment of arthritis. The efficacy of exercise therapy has been reviewed in adults with rheumatoid arthritis but not in children with juvenile idiopathic arthritis (JIA). OBJECTIVES: To assess the effects of exercise therapy on functional ability, quality of life and aerobic capacity in children with JIA. METHODS: Several electronic databases were searched up to October 2007 and references were tracked. The selection criteria were randomized controlled trials (RCTs) of exercise treatment in JIA. As for data collection and analysis, potentially relevant references were evaluated and all data were extracted by two review authors working independently. RESULTS: Three out of 16 identified studies met the inclusion criteria, with a total of 212 participants. All the included studies fulfilled at least seven of 10 methodological criteria. The outcome data of the following measures were homogenous and were pooled in a meta-analysis: functional ability (N=198; weighted mean difference [WMD] -0.07, 95% CI -0.22 to 0.08), quality of life (CHQ-PhS: N=115; WMD -3.96, 95% CI -8.91 to 1.00) and aerobic capacity (N=124; WMD 0.04, 95% CI -0.11 to 0.19). The results suggest that the outcome measures all favoured the exercise therapy but none were statistically significant. None of the studies reported negative effects of the exercise therapy. CONCLUSIONS: Overall, based on ''silver-level'' evidence there was no clinically important or statistically significant evidence that exercise therapy can improve functional ability, quality of life, aerobic capacity or pain. The included and excluded studies were all consistent about the adverse effects of exercise therapy; no short-term detrimental effects of exercise therapy were found in any study. Both included and excluded studies showed that exercise does not exacerbate arthritis. Although the short-term effects look promising, the long-term effect of exercise therapy remains unclear.

Headache during hemodialysis - an uncommon cause for a common problem.

A hemodialysis patient is described who was suffering from headache during his dialysis sessions. This was due to a neovascular glaucoma causing an increase in intraocular pressure (IOP) during dialysis sessions. After several months his headache decreased but his IOP measurements remained high with almost similar pre- and post dialysis values. Headache during hemodialysis may be due to glaucoma, but this can disappear with time, along with a disappearance in the increase in IOP during dialysis sessions.

Exercise therapy in juvenile idiopathic arthritis.

BACKGROUND: Exercise therapy is considered an important component of the treatment of arthritis. The efficacy of exercise therapy has been reviewed in adults with rheumatoid arthritis but not in children with juvenile idiopathic arthritis (JIA). OBJECTIVES: To assess the effects of exercise therapy on functional ability, quality of life and aerobic capacity in children with JIA. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (The Cochrane Library), MEDLINE (January 1966 to April 2007), CINAHL (January 1982 to April 2007), EMBASE (January 1966 to October 2007), PEDro (January 1966 to October 2007), SportDiscus (January 1966 to October 2007), Google Scholar (to October 2007), AMED (Allied and Alternative Medicine) (January 1985 to October 2007), Health Technologies Assessment database (January 1988 to October 2007), ISI Web Science Index to Scientific and Technical Proceedings (January 1966 to October 2007) and the Chartered Society of Physiotherapy website (http://www.cps.uk.org) were searched and references tracked. SELECTION CRITERIA: Randomised controlled trials (RCTs) of exercise treatment in JIA. DATA COLLECTION AND ANALYSIS: Potentially relevant references were evaluated and all data were extracted by two review authors working independently. MAIN RESULTS: Three out of 16 identified studies met the inclusion criteria, with a total of 212 participants. All the included studies fulfilled at least seven of 10 methodological criteria. The outcome data of the following measures were homogenous and were pooled in a meta-analysis: functional ability (n = 198; WMD -0.07, 95% CI -0.22 to 0.08), quality of life (CHQ-PhS: n = 115; WMD -3.96, 95% CI -8.91 to 1.00) and aerobic capacity (n = 124; WMD 0.04, 95% CI -0.11 to 0.19). The results suggest that the outcome measures all favoured the exercise therapy but none were statistically significant. None of the studies reported negative effects of the exercise therapy. AUTHORS' CONCLUSIONS: Overall, based on 'silver-level' evidence (www.cochranemsk.org) there was no clinically important or statistically significant evidence that exercise therapy can improve functional ability, quality of life, aerobic capacity or pain. The low number of available RCTs limits the generalisability. The included and excluded studies were all consistent about the adverse effects of exercise therapy; no short-term detrimental effects of exercise therapy were found in any study. Both included and excluded studies showed that exercise does not exacerbate arthritis. The large heterogeneity in outcome measures, as seen in this review, emphasises the need for a standardised assessment or a core set of functional and physical outcome measurements suited for health research to generate evidence about the possible benefits of exercise therapy for patients with JIA. Although the short-term effects look promising, the long-term effect of exercise therapy remains unclear.

Aerobic and anaerobic exercise capacity in children with juvenile idiopathic arthritis.

OBJECTIVE: To compare the aerobic and anaerobic exercise capacity of children with juvenile idiopathic arthritis (JIA) with healthy controls, to determine if there were differences based on disease onset type, and to examine the relationship between aerobic and anaerobic exercise capacity in children with JIA. METHODS: Sixty-two patients with JIA (mean +/- SD age 11.9 +/- 2.2 years, range 6.7-15.9) participated in this study. Aerobic exercise capacity was measured using a cardiopulmonary exercise test. Anaerobic exercise capacity was measured using the Wingate Anaerobic Exercise Test (WAnT). RESULTS: All patients were able to perform the cardiopulmonary exercise test and WAnT without adverse events. On average, the maximal oxygen uptake (VO(2peak)) and VO(2peak/kg) were 69.8% and 74.8%, respectively, of that predicted compared with healthy controls. Mean +/- SD power was 66.7% +/- 37.2% of that predicted compared with healthy children. Mean +/- SD peak power was 65.5% +/- 43.1% of that predicted compared with healthy children. There were significant differences between subgroups of JIA; the oligoarticular-onset group values did not significantly differ from healthy control values; the polyarticular rheumatoid factor positive-onset subgroup had the greatest impairment in both aerobic and anaerobic exercise capacity. The correlations of mean power and peak power with VO(2peak) were r = 0.884 and r = 0.697, respectively (P < 0.05). CONCLUSION: This study demonstrates that both the aerobic and anaerobic exercise capacity in children with JIA are significantly decreased. The WAnT might be a valuable adjunct to other assessment tools in the followup of patients with JIA.

DFT study of oxygen adsorption on modified nanostructured gold pyramids.

Periodic DFT calculations are used to predict and investigate the adsorption behavior of molecular oxygen on Au, Au/Pt, and Pt surfaces. To obtain an array of pyramids containing surface atoms with the lowest possible coordination number, a nano-modified surface consisting of a symmetrically "modified" (100) surface was used. The effect of atom substitution (organized alloying) is investigated. The adsorption of molecular oxygen on a pure gold pyramid is exothermic by 0.77 eV for the end-on adsorption mode. In the case of a pure platinum pyramid, the end-on adsorption mode was found to dissociate; however, a side-on geometry was encountered with an energy of adsorption of 2.3 eV. This value is in line with the fact that the adsorption energy of small molecules does not vary much on Pt surfaces with different indices. Additionally, some geometrically related trends of the surface deformation in relation to its composition and after adsorption of molecular oxygen are highlighted.

Is physical fitness decreased in survivors of childhood leukemia? A systematic review.

The aim of this review is to determine whether physical fitness, assessed by peak oxygen uptake (VO(2peak)) measurement, is reduced in survivors of acute lymphoblastic leukemia (ALL) compared to healthy children. A systematic literature search (up to June 2004) was performed using Medline, Sportdiscus, Cinahl, Embase, Cochrane and PEDro database and reference tracking. The VO(2peak) (ml kg(-1) min(-1)) reached during a maximal exercise test until volitional exhaustion was used as the main outcome for this review. In all, 17 studies were identified in the literature. Data from three studies (102 ALL survivors, age ranging from 7 to 19 years) were pooled in a meta-analysis. Although there was a significant heterogeneity between the included studies (P=0.0006), the standardized mean difference (SMD) value of -0.61 (P=0.07) indicated that VO(2peak) tended to be reduced in survivors of childhood ALL compared to healthy control subjects, that is, decrease of -5.97 ml kg(-1) min(-1) (95% confidence interval (CI): (-12.35, 0.41); P=0.07) or -13% (95 % CI: (-27, 0.004)). Physical fitness tends to be reduced in survivors of ALL during childhood, which suggests the need for this population group to engage in regular physical activities with the purpose of increasing their functional capacity. Although more research is needed, this functional improvement might ameliorate the quality of life of ALL survivors as physical and outdoors activities are an essential part of daily routine during childhood.

Abdominal stab wounds: a five-year patient review.

Over a period of 5 years, 101 patients were treated for abdominal stab wounds at our emergency department. Exploratory laparotomy was performed in 41 of these cases. The indication for laparotomy was set by clinical investigation in 20 cases, instrumental exploration in six patients, ultrasound in six, paracentesis in seven and computerized tomography scanning in two cases. A review of the results of the treatment of these abdominal stab wounds is compared with the literature. Routine laparotomy for this type of penetrating trauma to the abdomen proves to be no longer warranted. Clinical and especially diagnostic studies should be able to select patients in whom laparotomy should be performed. When these studies are unable to exclude severe injury, laparotomy remains more prudent than expectant observation.

The discovery of two new divergent STLVs has implications for the evolution and epidemiology of HTLVs.

We have isolated and characterised two divergent simian T-lymphotropic viruses (STLV), not belonging to the established human and simian T-lymphotropic virus lineages HTLV-1/STLV-1 and HTLV-2. STLV-L, from an Eritrean sacred baboon (Papio hamadryas), has been typed as a third type of simian T-lymphotropic virus, distinct from HTLV-1/STLV-1 and HTLV-2. The other virus, isolated from Congolese bonobos (Pan paniscus), is a distinct member of the HTLV-2 clade and has been designated STLV-2. The isolation of these two simian viruses shows that the spectrum of HTLVs/STLVs is larger than previously expected. Our data indicate that the two lineages STLV-L and HTLV-2/STLV-2 are of African origin, while the HTLV-1/STLV-1 lineage has been shown to be of Asian origin. These data, together with our phylogenetic analyses, suggest an African origin of the HTLV/STLV ancestor, which provides new clues about virus dissemination. Furthermore, the atypical serological profiles exhibited by STLV-L or STLV-2 infected animals in western blot, raise questions about the efficiency of current screening methods to type highly divergent HTLVs/STLVs. Considering the growing interest in xenotransplantations, more epidemiological and biological knowledge of simian and human T-lymphotropic viruses is necessary to estimate the risk of interspecies transmissions.

[Growing divergence inside primate T cell lymphotropic viruses]. / Groeiende divergentie binnen de primaat T-cell lymfotrope virussen.

During our studies on the evolution of the PTLVs, we have isolated and genomically characterized two divergent simian T-lymphotropic viruses, not belonging to the previously well-established PTLV lineages. STLV-PH969 has been isolated from an Eritrean sacred baboon (Papio hamadryas), with an HTLV-like indeterminate serological profile. The entire 8916 nt long genomic sequence, was obtained from a cDNA library of PH969 mRNA, in combination with a PCR based strategy. All open reading frames (ORF) common to all HTLV related viruses could be identified without important deletions or insertions. Sequence comparison of the STLV-PH969 genomic sequence with the HTLV-I and -II prototype sequences revealed that this virus is equidistantly related to HTLV-I and -II. A phylogenetic analysis on the envelope and regulatory Tax proteins conclusively proved the ancient separation of HTLV-I, -II and STLV-PH969. Together these data provided enough evidence to justify the classification of this virus as a new type of primate T-lymphotropic virus, designated PTLV-L. We isolated a second highly divergent virus from pygmy chimpanzees (bonobo's, Pan paniscus) housed in the Antwerp Zoo. The animals infected with this virus showed an aberrant HTLV-I like serological profile. The entire 8855 nt long genomic sequence of the STLV-PP1664 provirus was obtained by sequencing of overlapping PCR fragments. On this sequence, all ORFs common to all HTLV related viruses could be identified without any important deletions or insertions. Sequence comparison showed that the STLV-PP1664 proviral sequence was related to HTLV-II and the virus is called STLV-II. However, in all genomic regions, STLV-IIPP1664 was much more divergent from any of the HTLV-II subtypes than these are from each other. In order to further investigate the genomic relationship of STLV-LPH969 and STLV-IIPP1664 with HTLV-I and -II, we also analyzed the genomic organization of the pX region, which differs between HTLV-I and HTLV-II. In the STLV-LPH969 and STLV-IIPP1664 producing cell lines, 2 and 5 viral messengers could be detected respectively, potentially expressing 3 and 5 different accessory proteins respectively. The splicing pattern and the resulting proteins differ from those of HTLV-I and HTLV-II. In the light of the growing interest for xenotransplantation, the prevalence of distinct PTLVs in the wild and their capacity to cross the species barrier deserves further attention.

The simian T-lymphotropic virus STLV-PP1664 from Pan paniscus is distinctly related to HTLV-2 but differs in genomic organization.

We have isolated a highly divergent simian T-lymphotropic virus, STLV-PP1664, from a wild-caught bonobo (Pan paniscus). Previous phylogenetic analysis suggested that this virus represents an additional type of STLV but this has now become a matter of discussion. We have now obtained and analyzed the entire genome of STLV-PP1664. All major genes and their corresponding viral messengers were identified. Sequence comparison and phylogenetic analysis indicated that this virus, together with the closely related panp isolate, belongs to an early lineage within the PTLV-2 clade, differing from HTLV-2 by about 25%. In contrast to the HTLV-1 and HTLV-2 LTR, only two 21-bp repeats instead of three were found in the STLV-PP1664 LTR. Additional messengers, resulting from alternative splicing, potentially encode five different accessory proteins from open reading frames in the pX region: prorfI, porfII, ptorfV', and two isoforms of Rex. The amino acid sequences of these proteins are only distinctly related to the accessory proteins from HTLV-2. These data suggest a different genomic organization of the STLV-PP1664 pX region than that of HTLV-2. We conclude that STLV-PP1664, although related to HTLV-2, has some distinct features in the LTR and the pX regions, the impact of which needs further investigation. Although arguments pro and contra a distinct classification are nearly equally balanced, we propose to classify this virus as an STLV-2, designated STLV-2PP1664.