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Background A high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization has been reported among residents in geriatric long-term care facilities (LTCFs). Some studies indicate that MRSA might be imported from hospitals into LTCFs via resident transfer; however, other studies report that high MRSA prevalence might be caused by cross-transmission inside LTCFs. We aimed to assess which factors have a large impact on the high MRSA prevalence among residents of geriatric LTCFs. Methods We conducted a cohort study among 260 residents of four geriatric LTCFs in Japan. Dividing participants into two cohorts, we separately analyzed (1) the association between prevalence of MRSA carriage and length of LTCF residence (Cohort 1: n = 204), and (2) proportion of residents identified as MRSA negative who were initially tested at admission but subsequently identified as positive in secondary testing performed at ≥2 months after their initial test (Cohort 2: n = 79). Results Among 204 residents in Cohort 1, 20 (9.8%) were identified as positive for MRSA. Compared with residents identified as MRSA negative, a larger proportion of MRSA-positive residents had shorter periods of residence from the initial admission (median length of residence: 5.5 vs. 2.8 months), although this difference was not statistically significant (p = 0.084). Among 79 residents in Cohort 2, 60 (75.9%) were identified as MRSA negative at the initial testing. Of these 60 residents, only one (1.7%) had subsequent positive conversion in secondary MRSA testing. In contrast, among 19 residents identified as MRSA positive in the initial testing, 10 (52.6%) were negative in secondary testing. Conclusions The prevalence of MRSA was lower among residents with longer periods of LTCF residence than among those with shorter periods. Furthermore, few residents were found to become MRSA carrier after their initial admission. These findings highlight that MRSA in LTCFs might be associated with resident transfer rather than spread via cross-transmission inside LTCFs.

5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid (5,6-DiHETE) is an eicosapentaenoic acid-derived lipid metabolite, which we previously detected in inflamed mouse colon. In this study, we investigated the pathophysiological roles of 5,6-DiHETE in murine colitis and its underlying mechanisms of action, focusing on the effects on transient receptor potential vanilloid (TRPV) channel activity. Oral administration of dextran sodium sulfate (DSS, 2%, for 4 days) caused colon inflammation, which peaked on day 7 and gradually declined by day 18. 5,6-DiHETE concentration in colon tissue was significantly increased during the healing phase of colitis (days 9 to 18). In vitro study showed that pretreatment with 5,6-DiHETE (0.1-1 μM, 30 minutes) significantly inhibited endothelial barrier disruption induced by a TRPV4 agonist (GSK1016790A, 50 nM). Intracellular Ca2+ imaging also showed that pretreatment with 5,6-DiHETE (1 μM, 10 minutes) reduced GSK1016790A-induced intracellular Ca2+ increase in HEK293T cells overexpressing TRPV4. In vivo, intraperitoneal administration of 5,6-DiHETE (50 µg kg-1 day-1 ) during the healing phase accelerated the recovery from DSS-induced colitis. Pathological studies showed that the administration of 5,6-DiHETE inhibited edema formation and leukocyte infiltration in inflamed colon tissue. In conclusion, we identified 5,6-DiHETE as a novel endogenous TRPV4 antagonist, and we also demonstrated that its administration promotes the healing of colitis by inhibiting inflammatory responses.

Background: In response to coronavirus disease 2019 (COVID-19), the psychological distress of health care workers (HCWs) is overwhelming, irrespective of the extent of exposure to infected patients. Infection control and prevention (ICP) measures for mobile children and youths are indispensable to contemplate sustainable public health management, but it is difficult to define the clear trade-offs between ensuring virus-containing strategy and resuming ordinary childcare. Aim: To analyze the occupational distress and dilemma of HCWs working on the pediatric cancer ward as a representative model to conceptualize the core of anxiety at the childcare frontline. Methods: Qualitative and quantitative studies using an empirical phenomenological approach and questionnaire survey from 20 th April to 5 th May 2020. Results: High confidence in the institutional ICP measures is fundamental to maintain a strong social responsibility and resilience of HCWs against the crisis, but they are still under overwhelming anxiety within themselves, particularly about being infected to become an asymptomatic carrier who might pass the virus to patients. Both nursing staff and HCWs with less than 5 years of working experience perceived more intense psychological distress in comparison with physicians. Conclusion: We would like to suggest that target approaches, such as activating interpersonal communication and facilitating ICP adherence, are indispensable to maintain the safety climate among HCWs. Recognizing the psychological distress of childcare HCWs is important to mitigate their occupational distress, but also development of future public health strategy in the era of COVID-19.

Shwachman–Diamond syndrome (SDS), an autosomal recessive disorder characterized by bone marrow failure, exocrine pancreatic insufficiency, and skeletal abnormalities, is caused by mutations in the Shwachman–Bodian–Diamond syndrome (SBDS) gene, which plays a role in ribosome biogenesis. Although the causative genes of congenital disorders frequently involve regulation of embryogenesis, the role of the SBDS gene in early hematopoiesis remains unclear, primarily due to the lack of a suitable experimental model for this syndrome. In this study, we established induced pluripotent stem cells (iPSCs) from patients with SDS (SDS-iPSCs) and analyzed their in vitro hematopoietic and endothelial differentiation potentials. SDS-iPSCs generated hematopoietic and endothelial cells less efficiently than iPSCs derived from healthy donors, principally due to the apoptotic predisposition of KDR+CD34+ common hemoangiogenic progenitors. By contrast, forced expression of SBDS gene in SDS-iPSCs or treatment with a caspase inhibitor reversed the deficiency in hematopoietic and endothelial development, and decreased apoptosis of their progenitors, mainly via p53-independent mechanisms. Patient-derived iPSCs exhibited the hematological abnormalities associated with SDS even at the earliest hematopoietic stages. These findings will enable us to dissect the pathogenesis of multiple disorders associated with ribosomal dysfunction.

We investigate the transient coexistence state of the excitons and charge carriers in highly-pure diamond after an impulsive injection of excitons, by probing free electrons until the relaxation of carriers with the nanosecond time-resolved cyclotron resonance (TRCR) method. By analyzing the time profiles of the TRCR signal with a numerical solution of rate equations for exciton and charge carrier densities over a wide temperature range from 10 K to 261 K, the temperature dependence of the coefficient of two-body (Auger) collision of excitons, the rate of thermal dissociation of excitons, and exciton and electron lifetimes was extracted. The shift of exciton dissociation mechanisms from the Auger process below 40 K to the thermal ionization above 80 K was revealed for an initial density of excitons in the order of 1015 cm−3. We also found that the equilibrium between electrons and excitons is established within 100 ns above 80 K, when the thermal ionization of excitons dominates the dissociation process. These results provide fundamental understandings of transient carrier correlation in optoelectronic devices.

Baloxavir marboxil has been used for influenza treatment since March 2018 in Japan. After baloxavir treatment, the most frequently detected substitution is Ile38Thr in polymerase acidic protein (PA/I38T), and this substitution reduces baloxavir susceptibility in influenza A viruses. To rapidly investigate the frequency of PA/I38T in influenza A (H1N1)pdm09 and A (H3N2) viruses in clinical samples, we established a rapid real-time system to detect single nucleotide polymorphisms in PA, using cycling probe real-time PCR. We designed two sets of probes that were labeled with either 6-carboxyfluorescein (FAM) or 6-carboxy-X-rhodamine (ROX) to identify PA/I38 (wild type strain) or PA/I38T, respectively. The established cycling probe real-time PCR system showed a dynamic linear range of 101 to 106 copies with high sensitivity in plasmid DNA controls. This real-time PCR system discriminated between PA/I38T and wild type viruses well. During the 2018/19 season, 377 influenza A-positive clinical samples were collected in Japan before antiviral treatment. Using our cycling probe real-time PCR system, we detected no (0/129, 0.0%) influenza A (H1N1)pdm09 viruses with PA/I38T substitutions and four A (H3N2) (4/229, 1.7%) with PA/I38T substitution prior to treatment. In addition, we found PA/I38T variant in siblings who did not received baloxavir treatment during an infection caused by A (H3N2) that afflicted the entire family. Although human-to-human transmission of PA/I38T variant may have occurred in a closed environment, the prevalence of this variant in influenza A viruses was still limited. Our cycling probe-PCR system is thus useful for antiviral surveillance of influenza A viruses possessing PA/I38T.

Porcine edema disease (ED) is a toxemia caused by enteric infection with Shiga toxin 2e (Stx2e)-producing Escherichia coli (STEC). ED occurs most frequently during the weaning period and is manifested as emaciation associated with high mortality. In our experimental infection with a specific STEC strain, we failed to cause the suppression of weight gain in piglets, which is a typical symptom of ED, in two consecutive experiments. Therefore, we examined the effects of deprivation of colostrum on the sensitivity of newborn piglets to STEC infection. Neonatal pigs were categorized into two groups: one fed artificial milk instead of colostrum in the first 24 h after birth and then returned to the care of their mother, the other breastfed by a surrogate mother until weaning. The oral challenge with 1011 colony-forming units of virulent STEC strain on days 25, 26 and 27 caused suppression of weight gain and other ED symptoms in both groups, suggesting that colostrum deprivation from piglets was effective in enhancing susceptibility to STEC. Two successive STEC infection experiments using colostrum-deprived piglets reproduced this result, leading us to conclude that this improved ED piglet model is more sensitive to STEC infection than the previously established models.

Secondary expansion and/or evolution of aggressive subclones are associated with the disease progression and resistance to chemotherapy in neuroblastoma, and it is important to track the clonal changes during the treatment period. Cell-free (cf) DNA analysis, namely liquid biopsy, can detect the genomic change of tumor cells without surgical procedures. In this report, we showed that serial polymerase chain reaction-based cf DNA neuroblastoma proto-oncogene quantification is sensitive enough to evaluate the aggressive cellular characteristics of ALK/MYCN-coamplified neuroblastoma and stressed the promise of cf DNA analyses as a reliable molecular marker in advanced neuroblastoma.

We present multi-wavelength studies of optically-defined merging clusters, based on the Hyper Suprime-Cam Subaru Strategic Program. Luminous red galaxies, tracing cluster mass distributions, enable to identify cluster subhalos at various merging stages, and thus make a homogeneous sample of cluster mergers, which is unbiased with respect to the merger boost of the intracluster medium (ICM). We define, using a peak-finding method, merging clusters with multiple-peaks and single clusters with single-peaks from the CAMIRA cluster catalog. Stacked weak-lensing analysis indicates that our sample of the merging clusters is categorized into major mergers. The average halo concentration for the merging clusters is $\sim70\%$ smaller than that of the single-peak clusters, which agrees well with predictions of numerical simulations. The spatial distribution of subhalos is less centrally concentrated than the mass distribution of the main halo. The fractions of red galaxies in the merging clusters are not higher than those of the single-peak clusters. We find a signature of the merger boost of the ICM from stacked Planck Sunyaev-Zeldovich effect and ROSAT X-ray luminosity, but not in optical richness. The stacked X-ray surface brightness distribution, aligned with the main-subhalo pairs of low redshift and massive clusters, shows that the central gas core is elongated along the merger axis and overall gas distribution is misaligned by $\sim60$ deg. The homogeneous, unbiased sample of cluster mergers and multi-wavelength follow-up studies provide a unique opportunity to make a complete picture of merger physics over the whole process., Comment: 23 pages, 10 figures, 1 table : accepted for the publication in PASJ

Aim: To examine the genetic structure and global phylogeography of the endangered green sea turtle, Chelonia mydas, in light of past climatic events and current conservation needs. Location: Tropical and subtropical beaches around the world. Methods: We analysed 386 base pairs of the mitochondrial (mt)DNA control region of 4,878 individual nesting green turtle samples from 127 rookeries globally. We used phylogeographic analysis to assess how demographic history, dispersal and barriers to gene flow have led to the current distribution of mtDNA lineages. Results: We identified 11 divergent lineages that were tied to specific biogeographical regions. The phylogenetic analyses revealed an ancient origin for the species centred in the Indo-Pacific and more recent colonization of the Central/Eastern Pacific as well as the Atlantic Basin. Overall the phylogeographic structure was strong but with a clear pattern of regional connectivity among rookeries. A Large genetic separation was found where there were obvious barriers to dispersal such as between the Atlantic and Pacific oceans and across the Pacific Ocean, as well as less obvious barriers to dispersal. Admixture of mtDNA haplotype lineages was detected at latitudinal extremes across the Indian Ocean and western Pacific Ocean resulting in these areas being nucleotide diversity hotspots. The highest regional genetic diversity and high endemic richness was observed in the SW Pacific, NW Pacific, SW Indian and NW Indian oceans. Main conclusions: Past climatic fluctuations greatly affected the distribution of genetic diversity in the highly migratory green turtle. Our data suggest that past climatic events influenced local populations in different ways and the species appears to have survived the last glaciations in multiple glacial refugia.

Vitrification is widely used for assisted reproductive technology (ART). Most vitrification devices require the skillful placement of embryos into the carrier and aspiration of excessive vitrification solution.To evaluate the efficacy and safety of the Cryoroom as a vitrification device.Mouse and human embryos were vitrified with Cryoroom or Cryotop, and the developmental potency was assessed in vitro. Mouse monozygotic twin blastocysts were vitrified with Cryoroom or Cryotop for microarray analysis.In mouse and human embryos, there were no differences between the survival and developmental progress in each device. In silico, the Cryoroom device showed no changes, particularly in DNA methylation after vitrification compared with the Cryotop. These results showed that the form and function of the device may affect the gene expression levels in vitrified embryos.The Cryoroom represents a safe and potentially revolutionary vitrification device for ART.

Highly pathogenic avian H5 influenza viruses persist among poultry and wild birds throughout the world. They sometimes cause interspecies transmission between avian and mammalian hosts. H5 viruses possessing the HA of subclade 2.3.4.4, 2.3.2.1, 2.2.1, or 7.2 were detected between 2015 and 2018. To understand the neutralizing epitopes of H5-HA, we characterized 15 human monoclonal antibodies (mAbs) against the HA of H5 viruses, which were obtained from volunteers who received the H5N1 vaccine that contains a subclade 2.2.1 or 2.1.3.2 virus as an antigen. Twelve mAbs were specific for the HA of subclade 2.2.1, two mAbs were specific for the HA of subclade 2.1.3.2, and one mAb was specific for the HA of both. Of the 15 mAbs analyzed, nine, which were specific for the HA of subclade 2.2.1, and shared the VH and VL genes, possessed hemagglutination inhibition and neutralizing activities, whereas the others did not. A single amino acid substitution or insertion at positions 144&ndash, 147 in antigenic site A conferred resistance against these nine mAbs to the subclade 2.2.1 viruses. The amino acids at positions 144&ndash, 147 are highly conserved among subclade 2.2.1, but differ from those of other subclades. These results show that the neutralizing epitope including amino acids at positions 144&ndash, 147 is targeted by human antibodies, and plays a role in the antigenic difference between subclade 2.2.1 and other subclades.

The distributions of the pairwise line-of-sight velocity between galaxies and their host clusters are segregated according to the galaxy's colour and morphology. We investigate the velocity distribution of red-spiral galaxies, which represents a rare population within galaxy clusters. We find that the probability distribution function of the pairwise line-of-sight velocity $v_{\rm{los}}$ between red-spiral galaxies and galaxy clusters has a dip at $v_{\rm{los}} = 0$, which is a very odd feature, at 93\% confidence level. To understand its origin, we construct a model of the phase space distribution of galaxies surrounding galaxy clusters in three-dimensional space by using cosmological $N$-body simulations. We adopt a two component model that consists of the infall component, which corresponds to galaxies that are now falling into galaxy clusters, and the splashback component, which corresponds to galaxies that are on their first (or more) orbit after falling into galaxy clusters. We find that we can reproduce the distribution of the line-of-sight velocity of red-spiral galaxies with the dip with a very simple assumption that red-spiral galaxies reside predominantly in the infall component, regardless of the choice of the functional form of their spatial distribution. Our results constrain the quenching timescale of red-spiral galaxies to a few Gyrs, and the radius where the morphological transformation is effective as $r \sim 0.2 h^{-1} \rm{Mpc}$., 10 pages, 9 figures, accepted for publication in MNRAS

Human influenza A(H2N2) viruses emerged in 1957 and were replaced by A(H3N2) viruses in 1968. The antigenicity of human H2N2 viruses has been tested by using ferret antisera or mouse and human monoclonal antibodies. Here, we examined the antigenicity of human H2N2 viruses by using human plasma samples obtained from 50 aged individuals who were born between 1928 and 1933 and from 33 younger adult individuals who were born after 1962. The aged individuals possessed higher neutralization titers against H2N2 viruses isolated in 1957 and 1963 than those against H2N2 viruses isolated in 1968, whereas the younger adults who were born between 1962 and 1968 possessed higher neutralization titers against H2N2 viruses isolated in 1963 than those against other H2N2 viruses. Antigenic cartography revealed the antigenic changes that occurred in human H2N2 viruses during circulation in humans for 11 years, as detected by ferret antisera. These results show that even though aged individuals were likely exposed to more recent H2N2 viruses that are antigenically distinct from the earlier H2N2 viruses, they did not possess high neutralizing antibody titers to the more recent viruses, suggesting immunological imprinting of these individuals with the first H2N2 viruses they encountered and that this immunological imprinting lasts for over 50 years.

Thirty-nine groundwater samples were collected from wells near the Tavan Tolgoi and Oyu Tolgoi mines in Mongolia and at a relatively pristine site in northern Mongolia during August to September 2013, and analyzed for the concentrations of F−, NO3−, Hg, As, Al, V, Mn, Co, Ni, Cu, Zn, Se, Mo, Cd, Sb, and Pb. A probabilistic risk assessment found that >95% of the population in the areas was at risk from drinking well water. The hazard index (HI) was >1, indicating a non-carcinogenic risk to human health. At Oyu Tolgoi, the hazard quotient (HQ) of the As concentration (mean 6.63 μg/L) was >1. At the northern site, the 95th percentile HQ was 1. The ratios of nitrogen and oxygen stable isotopes indicated that NO3− contamination of groundwater at Oyu Tolgoi and Tavan Tolgoi was caused by livestock waste. Mercury accumulation in livestock was examined from concentrations in livestock forage and in hair and wool samples from livestock in the South Gobi region. Sheep wool had the same level of mercury as in Japan, but camel, horse, and goat hair had high levels.

Malignant rhabdoid tumor (MRT) is a rare, highly aggressive pediatric malignancy that primarily develops during infancy and early childhood. Despite the existing standard of intensive multimodal therapy, the prognosis of patients with MRT is dismal; therefore, a greater understanding of the biology of this disease is required to establish novel therapies. In this study, we identified a highly tumorigenic sub-population in MRT, based on the expression of CD146 (also known as melanoma cell adhesion molecule), a cell adhesion molecule expressed by neural crest cells and various derivatives. CD146+ cells isolated from four MRT cell lines by cell sorting exhibited enhanced self-renewal and invasive potential in vitro. In a xenograft model using immunodeficient NOD/Shi-scid IL-2Rγ-null mice, purified CD146+ cells obtained from MRT cell lines or a primary tumor exhibited the exclusive ability to form tumors in vivo. Blocking of CD146-related mechanisms, either by short hairpin RNA knockdown or treatment with a polyclonal antibody against CD146, effectively suppressed tumor growth of MRT cells both in vitro and in vivo via induction of apoptosis by inactivating Akt. Furthermore, CD146 positivity in immunohistological analysis of 11 MRT patient samples was associated with poor patient outcomes. These results suggest that CD146 defines a distinct sub-population in MRT with high tumorigenic capacity and that this marker represents a promising therapeutic target.

Effective conservation of globally distributed marine species relies on identification of demographically independent populations to ensure that management actions are directed at the appropriate scale. This identification is particularly challenging for species with complex life histories when local breeding populations have not been adequately sampled. We used mtDNA to analyze the population structure of loggerhead turtles from a total of 555 samples collected from 12 nesting sites in Japan in the Northwest Pacific, including previously unsampled rookeries in the Ryukyu Archipelago, for a comprehensive coverage of the nesting distribution. We identified a total of 9 haplotypes based on 820 bp of the mtDNA control region, including 5 variants of a single previously described 380 bp haplotype. We discovered that 1 haplotype (CcP1.1) previously rare in the North Pacific is common in the Ryukyu Archipelago. Based on analysis of haplotype frequencies, we found significant differentiation among regionally grouped nesting populations (analysis of molecular variance p < 0.0001, df = 8; pairwise FST ranging from 0.033 to 0.145). Our results provide evidence to support the recognition of 3 management units (MU) within the NW Pacific Regional Management Unit (RMU). These include (1) the Ryukyu MU that includes Okinawa, Okinoerabu and Amami, (2) Yakushima Island MU and (3) a Mainland MU that includes Bousou, Enshu-nada, Shikoku, Kii and Eastern Kyushu. These new data from Japan will provide important baseline data for global genetic stock assessments and contribute to our understanding of the population structure, ecology and life history of this migratory marine species in the northern Pacific.

The widely distributed colonization factor (CF) CS6 of enterotoxigenic Escherichia coli (ETEC) has gained importance over the years in terms of its structure and function. CS6 is an afimbrial assembly in contrast to the other ETEC CFs, which are mostly fimbrial. A recent study predicted a linear fibre model for recombinant chimeric CS6 and formation of oligomers in solution. In this study, we characterized the oligomeric assembly of CS6, purified from a clinical ETEC isolate and identified its existence in the WT strain. We found that purified CS6 forms a continuous array of higher order oligomers composed of two tightly associated subunits, CssA and CssB in an equal (1:1) stoichiometry. This oligomerization occurs by formation of (CssA-CssB)n complex where 'n' increases with the concentration. The diameter of CS6 oligomers also proportionally increases with concentration. More significantly, we showed CS6 oligomers to be spherical in shape instead of being linear fibres as predicted earlier and this was further confirmed by electron microscopy. We also showed CS6 assembled on the bacterial surface in the form of an oligomeric complex. This process depends on the expression of properly folded CssA and CssB together, guided by the chaperone CssC and usher CssD. In conclusion, our results provide evidence for the existence of concentration-dependent, spherical oligomers of CS6 comprising both the structural subunits in equal stoichiometry and the CS6 oligomeric complex on the ETEC surface.

Understanding the distribution range across the life history of endangered animals is crucial for effective conservation and management planning. However, endangered migratory green turtles with straight carapace lengths (SCLs) of

Enterotoxigenic Escherichia coli (ETEC) serotype O169:H41 has been an extremely destructive epidemic ETEC type worldwide. The strain harbors a large unstable plasmid that is regarded as responsible for its virulence, although its etiology has remained unknown. To examine its genetic background specifically on the unstable retention and responsibility in the unique adherence to epithelial cells and enterotoxin production, the complete sequence of a plasmid, pEntYN10, purified from the serotype strain was determined. The length is 145,082 bp; its GC content is 46.15%. It contains 182 CDSs, which include 3 colonization factors (CFs), an enterotoxin, and large number of insertion sequences. The repertory of plasmid stability genes was extraordinarily scant. Uniquely, results showed that 3 CFs, CS6, CS8 (CFA/III)-like, and K88 (F4)-like were encoded redundantly in the plasmid with unique variations among previously known subtypes. These three CFs preserved their respective gene structures similarly to those of other ETEC strains reported previously with unique sequence variations respectively. It is particularly interesting that the K88-like gene cluster of pEntYN10 had 2 paralogous copies of faeG, which encodes the major component of fimbrial structure. It remains to be verified how the unique variations found in the CFs respectively affect the affinity to infected cells, host range, and virulence of the ETEC strain.

Velocity dispersions have been employed as a method to measure masses of clusters. To complement this conventional method, we explore the possibility of constraining cluster masses from the stacked phase space distribution of galaxies at larger radii, where infall velocities are expected to have a sensitivity to cluster masses. First, we construct a two component model of the three-dimensional phase space distribution of haloes surrounding clusters up to 50 $h^{-1}$Mpc from cluster centres based on $N$-body simulations. We find that the three-dimensional phase space distribution shows a clear cluster mass dependence up to the largest scale examined. We then calculate the probability distribution function of pairwise line-of-sight velocities between clusters and haloes by projecting the three-dimensional phase space distribution along the line-of-sight with the effect of the Hubble flow. We find that this projected phase space distribution, which can directly be compared with observations, shows a complex mass dependence due to the interplay between infall velocities and the Hubble flow. Using this model, we estimate the accuracy of dynamical mass measurements from the projected phase space distribution at the transverse distance from cluster centres larger than $2h^{-1}$Mpc. We estimate that, by using $1.5\times 10^5$ spectroscopic galaxies, we can constrain the mean cluster masses with an accuracy of 14.5\% if we fully take account of the systematic error coming from the inaccuracy of our model. This can be improved down to 5.7\% by improving the accuracy of the model., 13 pages, 15 figures

We report on three cases of pediatric acute lymphoblastic leukemia presenting with bone pain and arthralgia as initial symptoms. At the first visit, their primary signs were recurrent bone pain and arthralgia, without significant peripheral blood abnormalities. It took 2-4 months to confirm the diagnosis from the onset of arthralgia due to this atypical presentation of the disease. Definitive diagnosis was obtained by bone marrow examination, and in all cases, complete remission was achieved by chemotherapy. As a feature of imaging, MRI exhibited diffuse bone marrow signal changes in T1-weighted images, and FDG-PET showed extensive abnormal bone marrow uptakes. In cases 2 and 3, it was difficult to diagnose by bone marrow aspiration from the iliac bone, but definitive diagnosis was obtained by bone marrow aspiration from the tibia, in which FDG-PET showed increased uptake. FDG-PET was therefore considered useful for the selection of bone marrow aspiration sites. In cases presenting with recurrent migratory bone pain and arthralgia, we need to consider performing bone marrow aspiration and imaging, such as MRI and FDG-PET, for early diagnosis and treatment of leukemia.