Role of ultrasonography in diagnosing early rheumatoid arthritis and remission of rheumatoid arthritis - a systematic review of the literature

Introduction

Ultrasonography (US) might have an added value to clinical examination in diagnosing early rheumatoid arthritis (RA) and assessing remission of RA. We aimed to clarify the added value of US in RA in these situations performing a systematic review.

Methods

A systematic literature search was performed for RA, US, diagnosis and remission. Methodological quality was assessed; the wide variability in the design of studies prohibited pooling of results.

Results

Six papers on the added value of US diagnosing early RA were found, in which at least bilateral metacarpophalangeal (MCP), wrists and metatarsophalangeal (MTP) joints were scanned. Compared to clinical examination, US was superior with regard to detecting synovitis and predicting progression to persistent arthritis or RA. Eleven papers on assessing remission were identified, in which at least the wrist and the MCP joints of the dominant hand were scanned. Often US detected inflammation in patients clinically in remission, irrespective of the remission criteria used. Power Doppler signs of synovitis predicted X-ray progression and future flare in patients clinically in remission.

Conclusions

US appears to have added value to clinical examination for diagnosing of RA when scanning at least MCP, wrist and MTP joints, and, when evaluating remission of RA, scanning at least wrist and MCP joints of the dominant hand. For both purposes primarily power Doppler US might be used since its results are less equivocal than those of greyscale US.     

Relationship among estradiol, cortisol and intensity of estrous behavior in dairy cattle

Economic profitability of a dairy farm is based, in part, on the calving interval of the cows. The optimal interval is 365 d. To achieve this, the cow needs to be pregnant within 85 d post partum. The first and most problematic step in this process is the determination of the optimal time for insemination, which is based on estrous behavior. The expression of estrous behavior, however, is at a low level in modem dairy herds, resulting in low detection rates and longer calving intervals. In the present study, a point scale was used to monitor postpartum, nonpregnant cows for estrous symptoms. Frequent blood samples were taken around estrus, and the cows were fit with pedometers to measure their activity. Correlations between the occurrence of symptoms of estrus and levels of estradiol and cortisol were then analyzed. Standing heat, the standard symptom of estrus, was observed in only 53% of the cows. A high correlation of 0.7 was found between estradiol concentration and estrous behavior. This was empasized by the fact that the estradiol level reached its highest level of 7.76 + 2.39 (SD) pg/mL at the same time as the highest behavior score. The highest pedometer readout lagged 8 h behind this moment. Cortisol levels did not exceed the physiological levels in rest situations but showed an increase at the time estrous behavior was at its maximum. The present study showed that standing heat is not the primary symptom for detecting estrus in cows. Pedometers are a useful aid but they have to be read several times a day. The high correlation between the visual symptoms of estrus and estradiol concentrations indicates that visual estrus detection is an efficient, reliable way to determine the right time for insemination.     

Physical mapping of rDNA genes corroborates allopolyploid origin in apomictic Brachiaria brizantha

Brachiaria (Trin.) Griseb belongs to the family Poaceae, and within the genus, apomixis or sexuality is present in different accessions of the same species. The majority of Brachiaria species are polyploid and apomictic, making strategies for crop improvement by breeding very intricate. In spite of the high frequency of apomictic polyploids, the relationship of polyploidy and hybridization with apomixis in Brachiaria is still unclear. Further analysis requires detailed knowledge regarding the genomic composition of the polyploids. The present work introduces the use of fluorescent in situ hybridization (FISH) into cytogenetic analysis of Brachiaria. Physical mapping of heterologous rDNA sequences, associated with conventional karyotyping of the B. brizantha diploid sexual (BRA 002747) and the tetraploid apomictic (BRA000591) accessions, provided evidence of the latter being of allopolyploid origin. Based on our results and on previous knowledge on apomixis in B. brizantha, we suggest that the origin of apomixis was probably a consequence of hybridization.     

Influence of anabolic combinations of an androgen plus an estrogen on biochemical pathways in bovine uterine endometrium and ovary

The application of anabolic steroids in food producing animals is forbidden in the EU since 1988, but the abuse of such drugs is a potential problem. The existing test systems are based on known compounds and can be eluded by newly emerging substances. The examination of physiological effects of anabolic hormones on different tissues to indirectly detect misuse might overcome this problem. Two studies were conducted with post-pubertal 24-months old Nguni heifers and pre-pubertal female 2-4 weeks old Holstein Friesian calves, respectively. The animals of the accordant treatment groups were administered combinations of estrogenic and androgenic compounds. The measurement of the gene expression pattern was undertaken with RT-qPCR. Target genes of different functional groups (receptors, angiogenesis, steroid synthesis, proliferation, apoptosis, nutrient metabolism and others) have been quantified. Several biochemical pathways were shown to be influenced by anabolic treatment. Both studies identified significant regulations in steroid and growth factor receptors (AR, ERβ, LHR, FSHR, Flt-1, PR, IGF-1R, Alk-6), angiogenic and tissue remodeling factors (VEGFs, FGFs, BMPs, ANGPT-2, MMPs, TIMP-2, CTSB), steroid synthesis (S5A1, HSD17, CYP19A1), proliferation (TNFα, IGF-1, IGFBPs, p53, c-fos; CEBPD, c-kit), apoptosis (CASP3, FasL, p53) and others (C7, INHA, STAR). Several genes were regulated to opposite directions in post-pubertal compared to pre-pubertal animals. PCA for Nguni heifers demonstrated a distinct separation between the control and the treatment group. In conclusion, anabolics modify hormone sensitivity and steroid synthesis, and they induce proliferative effects in the whole reproductive tract (uterus and ovary) as well as anti-angiogenic effects in the ovary. However, the extent will depend on the developmental stage of the animals.     

Experimental inoculation of male rats with Coxiella burnetii: successful infection but no transmission to cage mates

Beginning in 2007, the largest human Q fever outbreak ever described occurred in the Netherlands. Dairy goats from intensive farms were identified as the source, amplifying Coxiella burnetii during gestation and shedding large quantities during abortions. It has been postulated that wild rodents are reservoir hosts from which C. burnetii can be transmitted to domestic animals and humans. However, little is known about the infection dynamics of C. burnetii in wild rodents. The aim of this study was to investigate whether brown rats (Rattus norvegicus) can be experimentally infected with C. burnetii and whether transmission to a cage mates occurs. Fourteen male brown rats (wild type) were intratracheally or intranasally inoculated with a Dutch C. burnetii isolate obtained from a goat. At 3 days postinoculation, a contact rat was placed with each inoculated rat. The pairs were monitored using blood samples and rectal and throat swabs for 8 weeks, and after euthanasia the spleens were collected. Rats became infected by both inoculation routes, and detection of C. burnetii DNA in swabs suggests that excretion occurred. However, based on the negative spleens in PCR and the lack of seroconversion, none of the contact animals was considered infected; thus, no transmission was observed. The reproduction ratio R(0) was estimated to be 0 (95% confidence interval = 0 to 0.6), indicating that it is unlikely that rats act as reservoir host of C. burnetii through sustained transmission between male rats. Future research should focus on other transmission routes, such as vertical transmission or bacterial shedding during parturition.     

Assessing the impact of feline immunodeficiency virus and bovine tuberculosis co-infection in African lions

Bovine tuberculosis (BTB), caused by Mycobacterium bovis, is a disease that was introduced relatively recently into the Kruger National Park (KNP) lion population. Feline immunodeficiency virus (FIV(ple)) is thought to have been endemic in lions for a much longer time. In humans, co-infection between Mycobacterium tuberculosis and human immunodeficiency virus increases disease burden. If BTB were to reach high levels of prevalence in lions, and if similar worsening effects would exist between FIV(ple) and BTB as for their human equivalents, this could pose a lion conservation problem. We collected data on lions in KNP from 1993 to 2008 for spatio-temporal analysis of both FIV(ple) and BTB, and to assess whether a similar relationship between the two diseases exists in lions. We found that BTB prevalence in the south was higher than in the north (72 versus 19% over the total study period) and increased over time in the northern part of the KNP (0-41%). No significant spatio-temporal differences were seen for FIV(ple) in the study period, in agreement with the presumed endemic state of the infection. Both infections affected haematology and blood chemistry values, FIV(ple) in a more pronounced way than BTB. The effect of co-infection on these values, however, was always less than additive. Though a large proportion (31%) of the lions was co-infected with FIV(ple) and M. bovis, there was no evidence for a synergistic relation as in their human counterparts. Whether this results from different immunopathogeneses remains to be determined.     

Matita, a new retroelement from peanut: characterization and evolutionary context in the light of the Arachis A–B genome divergence

Cultivated peanut is an allotetraploid with an AB-genome. In order to learn more of the genomic structure of peanut, we characterized and studied the evolution of a retrotransposon originally isolated from a resistance gene analog (RGA)-containing bacterial artificial chromosome (BAC) clone. It is a moderate copy number Ty1-copia retrotransposon from the Bianca lineage and we named it Matita. Fluorescent in situ hybridization (FISH) experiments showed that Matita is mainly located on the distal regions of chromosome arms and is of approximately equal frequency on both A- and B-chromosomes. Its chromosome-specific hybridization pattern facilitates the identification of individual chromosomes, a useful cytogenetic tool considering that chromosomes in peanut are mostly metacentric and of similar size. Phylogenetic analysis of Matita elements, molecular dating of transposition events, and an estimation of the evolutionary divergence of the most probable A- and B-donor species suggest that Matita underwent its last major burst of transposition activity at around the same time of the A- and B-genome divergence about 3.5 million years ago. By probing BAC libraries with overgos probes for Matita, resistance gene analogues, and single- or low-copy genes, it was demonstrated that Matita is not randomly distributed in the genome but exhibits a significant tendency of being more abundant near resistance gene homologues than near single-copy genes. The described work is a further step towards broadening the knowledge on genomic and chromosomal structure of peanut and on its evolution.     

Induction and recovery of copy number variation in banana through gamma irradiation and low‐coverage whole‐genome sequencing

Traditional breeding methods are hindered in bananas due to the fact that major cultivars are sterile, parthenocarpic, triploid and thus clonally propagated. This has resulted in a narrow genetic base and limited resilience to biotic and abiotic stresses. Mutagenesis of in vitro propagated bananas is one method to introduce novel alleles and broaden genetic diversity. We previously established a method for the induction and recovery of single nucleotide mutations generated with the chemical mutagen EMS. However, officially released mutant banana varieties have been created using gamma rays, a mutagen that can produce large genomic insertions and deletions (indels). Such dosage mutations may be important for generating observable phenotypes in polyploids. In this study, we establish a low‐coverage whole‐genome sequencing approach in triploid bananas to recover large genomic indels caused by treatment with gamma irradiation. We first evaluated the commercially released mutant cultivar ‘Novaria’ and found that it harbours multiple predicted deletions, ranging from 0.3 to 3.8 million base pairs (Mbp). In total, predicted deletions span 189 coding regions. To evaluate the feasibility of generating and maintaining new mutations, we developed a pipeline for mutagenesis and screening for copy number variation in Cavendish bananas using the cultivar ‘Williams’. Putative mutations were recovered in 70% of lines treated with 20 Gy and 60% of the lines treated with 40 Gy. While deletion events predominate, insertions were identified in 20 Gy‐treated material. Based on these results, we believe this approach can be scaled up to support large breeding projects.     

Starch as a sugar reservoir for nematode-induced syncytia

The plant parasitic nematode Heterodera schachtii invades the roots of Arabidopsis thaliana to induce nematode feeding structures in the central cylinder. During nematode development, the parasites feed exclusively from these structures. Thus, high sugar import and specific sugar processing of the affected plant cells is crucial for nematode development. In the present work, we found starch accumulation in nematode feeding structures and therefore studied the expression genes involved in the starch metabolic pathway. The importance of starch synthesis was further shown using the Atss1 mutant line. As it is rather surprising to find starch accumulation in cells characterised by a high nutrient loss, we speculate that starch serves as long- and short-term carbohydrate storage to compensate the staggering feeding behaviour of the parasites.Key words: Heterodera schachtii, Arabidopsis, nematode, starch metabolism, syncytiaThe obligate plant parasitic nematode Heterodera schachtii is entirely dependent on a system of nutrient supply provided by the plant. Host plants—among those the model plant Arabidopsis thaliana—have to endure invasion of second stage juveniles and the establishment of nematode feeding structures in the plant''s vascular cylinder. For induction of the specific feeding structures, the juveniles pierce one single plant cell with their stylet and inject secretions, thus triggering the formation of a syncytium by local cell walls dissolutions.¹ Further, the central vacuole of the syncytial cells disintegrates, nuclei enlarge and many organelles proliferate.¹ About 24 hours after feeding site induction, the nematode juveniles start feeding in repetitive cycles.² Syncytia have previously been described as strong sinks in the plant''s transport system.³ Thus, in the recent years several studies were carried out to discover solute supply to syncytial cells.^4–7 To our present knowledge, syncytia are symplasmically isolated in the first days of nematode development. During that period, the nematodes depend on transport protein activity in the syncytia plasmamembranes. At later stages plasmodesmata appear to open to the phloem elements, facilitating symplasmic transport.Incoming solutes may either be taken up by the feeding nematode or are synthesised and catalysed by the syncytium''s metabolism. Due to the microscopically observable high density of the cytosol¹ and the increased osmotic pressure,⁸ syncytia appear to accumulate high solute concentrations. In fact, significantly increased sucrose levels have been found in syncytia in comparison to non-infected control roots.⁷ In case of high sugar levels, plant cells generally synthesize starch in order to reduce emerging osmotic stress.⁹ The aim of the work of Hofmann et al.,¹⁰ was to elucidate if starch is utilised as carbohydrate storage in nematode-induced syncytia and to study expression of genes involved in starch metabolism with an emphasis on nematode development.Starch levels of nematode induced syncytia and roots of non-infected plants grown on sand/soil culture were measured by high performance liquid chromatography (HPLC). The results showed a high accumulation of starch in syncytia that was steadily decreasing during nematode development. The accumulation of starch could further be localised within syncytial cells by electron microscopy. Based on these results, we studied the gene expression of the starch metabolic pathway by Affymetrix gene chip analysis. About half of the 56 involved genes were significantly upregulated in syncytia compared to the control and only two genes were significantly downregulated. Thus, the high induction of the gene expression is consistent with the high starch accumulation. Finally, we applied an Arabidopsis mutant line lacking starch synthase I expression that has been described previously.¹¹ Starch synthase I was the second highest upregulated gene in syncytia. It catalyses the linkage of ADP-glucose to the non-reducing end of an a-glucan, forming the linear glucose chains of amylopectin. In a nematode infection assay we were able to prove the significant importance of the gene for nematode development.With the presented results, we can unambiguously prove the accumulation of starch and the induction of the gene expression of the starch metabolic pathway in nematode-induced syncytia. The primary question however is: why do syncytia accumulate soluble sugars and starch although their metabolism is highly induced and nematodes withdraw solutes during continuously repeating feeding cycles?One explanation may be found where least expected—in nematode feeding. It is the feeding activity that induced solute import mechanisms into syncytia resulting in a newly formed sink tissue. However, during moulting events to the third, the fourth juvenile stage and to the adult stage nematodes interrupt feeding for about 20 hours.² During this period sugar supply mechanisms will most probably not be altered thus leading to increasing levels of sugars in the syncytium. Starch may serve as short-term carbohydrate buffering sugar excess. Further, starch may serve as long-term carbohydrate storage during nematode development. In the early stages of juvenile development nematodes withdraw considerably small quantities (about 0,8-times the syncytium volume a day).¹² At later stages, nutrient demand increases so that adult fertilised females require 4-times the syncytium volume per day in order to accomplish egg production.¹² Thus, excessive sugar supply in the first days may be accumulated as starch that gets degraded at later stages when more energy is required from the parasites. Consequently, starch reserve serves as both short-term and long-term carbohydrate storage in nematode-induced syncytia in order to buffer changing feeding pattern of the parasites.? Open in a separate windowFigure 1Arabidopsis wild-type Columbia-0 plants were grown in sand/soil culture. Nematode-induced syncytia and non-infected control roots were harvested at 10, 15 and 20 days after inoculation (dai) and starch content was measured as glucose (Glc) equivalents. Values are means ± SE, n = 3. Different letters indicate significant variations (p < 0.05). © ASPBOpen in a separate windowFigure 2Transmission electron microscope picture of a cross-section of a syncytium associated with female fourth stage juvenile (H. schachtii) induced in roots of Arabidopsis. Bar = 2 µm. S, syncytium; Se, sieve tube; arrow, plastid; asterisk, starch granule. © ASPB