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Poikiloderma with neutropenia (PN) Clericuzio type (OMIM #604173) is a rare disease with areas of skin hyper- and hypopigmentation caused by biallelic USB1 variants. The current study was spurred by poor healing of a perianal tear wound in one affected child homozygous for c.266-1G>A (p.E90Sfster8) mutation, from a family reported previously. Treatment with G-CSF/CSF3 or GM-CSF/CSF2 transiently increased neutrophil/monocytes count with no effect on wound healing. Analysis of peripheral blood revealed a lack of non-classical (CD14+/−CD16+) monocytes, associated with a systemic inflammatory cytokine profile, in the two affected brothers. Importantly, despite normal expression of cognate receptors, monocytes from PN patients did not respond to M-CSF or IL-34 in vitro, as determined by cytokine secretion or CD16 expression. RNAseq of monocytes showed 293 differentially expressed genes, including significant downregulation of GATA2, AKAP6 and PDE4DIP that are associated with leucocyte differentiation and cyclic adenosine monophosphate (cAMP) signalling. Notably, the plasma cAMP was significantly low in the PN patients. Our study revealed a novel association of PN with a lack of non-classical monocyte population. The defects in monocyte plasticity may contribute to disease manifestations in PN and a defective cAMP signalling may be the primary effect of the splicing errors caused by USB1 mutation.  相似文献   
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This study examined the genetic complexity of three equine herpesvirus 1 (EHV-1) defective interfering particles (DIP) and found the DIP genomes to range from 5.9 kbp to 7.3 kbp in total size. Each DIP contains an identical 5′ end (∼1.9 kb) that harbors UL3 and UL4 genes that are 100% identical to those of the infectious virus. DIP2 and DIP3 contain a previously described unique IR4/UL5 (EICP22/EICP27) hybrid gene (Hyb1.0). The DIP1 genome, however, appears to be generated from a different recombination event which results in the formation of a new distinct hybrid ORF. The new ORF (Hyb2.0) is comprised of 684 bp from the 5′ end of IR4 fused to 45 bp from the 3′ terminus of UL5. In contrast to Hyb1.0, the UL5 sequences present in Hyb2.0 are not in-frame. Thus, the Hyb2.0 protein is comprised of 228 residues from IR4 linked to a sequence of 15 amino acids that result from a frameshifted reading of UL5 sequences. Western blot analysis confirmed that the Hyb2.0 ORF is expressed during persistent infection to produce a family of proteins that migrate at 36–42 kDa. Fluorescence microscopy revealed that both Hyb proteins display diffuse cytoplasmic localization patterns dissimilar to the nuclear localization patterns of both IR4 and UL5. Neither Hyb protein, however, disrupts the nuclear entry of the EHV-1 immediate-early, IR4, or UL5 proteins or cellular TATA box binding protein (TBP) previously shown to interact with both IR4 or UL5 in productive infection. DIP genomic segments (∼3.5–5.0 kbp) downstream of the 100% conserved origin of replication are highly variable among the three DIP genomes and contain large areas of repetitive sequences. The possibility that the non-coding sequences play a role in viral interference and/or persistent infection remains to be determined.  相似文献   
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Interstitial lung disease (ILD) in children (chILD) is a heterogeneous group of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. The pathogenesis of the various chILD is complex and the diseases share common features of inflammatory and fibrotic changes of the lung parenchyma that impair gas exchanges. The etiologies of chILD are numerous. In this review, we chose to classify them as ILD related to exposure/environment insults, ILD related to systemic and immunological diseases, ILD related to primary lung parenchyma dysfunctions and ILD specific to infancy. A growing part of the etiologic spectrum of chILD is being attributed to molecular defects. Currently, the main genetic mutations associated with chILD are identified in the surfactant genes SFTPA1, SFTPA2, SFTPB, SFTPC, ABCA3 and NKX2-1. Other genetic contributors include mutations in MARS, CSF2RA and CSF2RB in pulmonary alveolar proteinosis, and mutations in TMEM173 and COPA in specific auto-inflammatory forms of chILD. However, only few genotype-phenotype correlations could be identified so far. Herein, information is provided about the clinical presentation and the diagnosis approach of chILD. Despite improvements in patient management, the therapeutic strategies are still relying mostly on corticosteroids although specific therapies are emerging. Larger longitudinal cohorts of patients are being gathered through ongoing international collaborations to improve disease knowledge and targeted therapies. Thus, it is expected that children with ILD will be able to reach the adulthood transition in a better condition.  相似文献   
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《Journal of hand therapy》2023,36(2):294-301
Study DesignNarrative review and case series.IntroductionThe relative motion approach has been applied to rehabilitation following flexor tendon repair. Positioning the affected finger(s) in relatively more metacarpophalangeal joint flexion is hypothesized to reduce the tension through the repaired flexor digitorum profundus by the quadriga effect. It is also hypothesized that altered patterns of co-contraction and co-inhibition may further reduce flexor digitorum profundus tension, and confer protection to flexor digitorum superficialis.MethodsWe reviewed the existing literature to explore the rationale for using relative motion flexion orthoses as an early active mobilization strategy for patients after zone I-III flexor tendon repairs. We used this approach within our own clinic for the rehabilitation of a series of patients presenting with zone I-II flexor tendon repair. We collected routine clinical and patient reported outcome data.ResultsWe report published outcomes of the clinical use of relative motion flexion orthoses with early active motion, implemented as the primary rehabilitation approach after zone I-III flexor digitorum repairs. We also report novel outcome data from 18 patients.DiscussionWe discuss our own experience of using relative motion flexion as a rehabilitation strategy following flexor tendon repair. We explore orthosis fabrication, rehabilitation exercises and functional hand use.ConclusionsThere is currently limited evidence informing use of relative motion flexion orthoses following flexor tendon repair. We highlight key areas for future research and describe a current pragmatic randomized controlled trial.  相似文献   
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The purpose of this study was to determine the relationship between BMD and childhood obesity. We examined 1070 obese children (722 boys and 348 girls) aged 7 to 15 years. Their mean relative weight, as a percentage of the standard weight for age, height, and sex, was 152.9 ± 14%. BMD was assessed, by a digital image processing method, in the second metacarpal bone of the left hand. We compared our results with those of healthy nonobese Japanese children based on both chronological and bone age. Mean BMD values for bone age in the obese children were significantly higher than those in control groups in boys aged 11 years and under and girls 9 years and under. On the other hand, in boys over 12 years old, BMD values for bone age were lower than those in the control groups. In girls over 11 years old, BMD values tended to be lower than those in the control groups. In conclusion, we studied the BMD of obese children from the point of view of advanced bone age. Our results showed that BMD was higher than in prepubertal obese children, but a low BMD value was found after puberty, due to poor gain of BMD during puberty. It is important to prevent obesity in childhood in order to prevent the low BMD after puberty.  相似文献   
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We present a case of metastatic testicular immature teratomathat was successfully treated despite resistance to standardchemotherapy and unsuccessful salvage surgery. At first, BEP(bleomycin, etoposide and cisplatin) treatment was performedbut failed. The patient underwent incomplete retroperitoneallymph node dissection. He was then referred to us. By the timeof the referral lung and mediastinal lymph node metastasis hadappeared and para-aortic lymph node metastasis had grown larger.We administered the DIP (docetaxel, ifosfamide and cisplatin)regimen as a second line chemotherapy, which was effective with82% reduction of para-aortic lymph nodes, 88% of mediastinallymph nodes and 85% of lung metastasis. We performed para-aorticlymph node dissection followed by resection of lung metastasisand mediastinal lymph node dissection. The patient is now followed-upat the outpatient clinic without evidence of recurrent disease3.5 years after the last surgery.  相似文献   
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INTRODUCTION: Arthrodesis of the distal interphalangeal joint (DIPJ) is an accepted operative procedure to treat osteoarthritis, instability and joint deformity. There is a wide spectrum of recommended operative techniques including cerclage wires, headless screws, bio-resorbable pins and lag screws. Lag screw fixation remains one of the most accepted methods of fixation; however, problems can occur in particular subsidence of the screw head leading to loss of compression and prominence of the screw head in the finger tip necessitating removal. We describe here a new technique of DIPJ arthrodesis that avoids these problems. METHODS AND PATIENTS: The technique is described here in detail, and clinical results are given for 18 joints (17 patients) followed-up at a mean 24 months (range 6-44). RESULTS: Mean post-operative DASH score was 15. There were no cases of non-union; only four complications were seen, one case of nail growth disturbance and one of early screw breakage necessitating revision. Two infections necessitated early hardware removal although both arthodesis were united. CONCLUSION: The technique is simple and reliable giving consistent clinical results.  相似文献   
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随着现代医院数字化建设的进一步发展,各种信息系统将越来越多的被投入使用。不同信息系统的构架设计、实现手段和开发环境都有差异,一般而言这些系统之间无法直接进行数据交互。医院需要建立一个提供各个子系统之间高效数据交互的集成平台,结合业务流程实现业务的跨系统整合。文章从医院数据集成平台的设想和构建实际出发,提出了数据集成平台设计理念、构架模块方面的理论设想,并将在实际建设中加以进一步验证和落实。  相似文献   
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