Exploring the Parameters of China's Economic Influence.

To what extent do China's linkages to the global economy translate into political influence in other countries? This topic is the focus of copious amounts of policy and scholarly attention in the USA and around the world. Yet without thoughtful conceptualization of key assumptions and creation of research designs that allow identification of mechanisms of potential influence, we cannot gain an accurate understanding of Chinese influence. How can we assess Beijing's intentions? Through what mechanisms-both intended and unintended-might influence arise, and under what conditions is influence most likely to occur? To what degree are Chinese companies agents of the state and therefore tools of economic statecraft? What factors condition how host countries react to economic ties with China? In this article, we explore existing scholarship on these questions, and assess promising directions for future research.

Clinical management in mixed gonadal dysgenesis with chromosomal mosaicism: Considerations in newborns and adolescents.

Individuals born on the spectrum of genetic abnormalities known as mixed gonadal dysgenesis (MGD) have a wide range of anatomical findings and management can be challenging in the newborn and adolescent. Historically, many individuals with MGD have undergone gonadectomy to avert the risk of gonadal malignancy. However, gonadectomy deprives patients of the benefits of their endogenous hormones, potential fertility, and in the case with MGD, has historically been done prior to addressing gender identity. Some patient advocates have proposed a delayed approach to surgical reconstructions and/or gonadectomy in other differences/disorders of sex development (DSD), particularly in patients with congenital adrenal hyperplasia and androgen insensitivity syndrome. In many areas of the world, there continues to be a shift toward delayed reconstructions and hesitancy regarding irreversible gonadectomy. To date, no clinical management protocol addressing these issues from a patient-centered approach has been described. We review what is known about malignancy risk and propose a management protocol for those with MGD that involves shared decision making regarding the gonads and addresses the long-term challenges with regard to gender and anatomy.

De novo missense variants in PPP2R5D are associated with intellectual disability, macrocephaly, hypotonia, and autism.

Protein phosphatase 2A (PP2A) is a heterotrimeric protein serine/threonine phosphatase and is involved in a broad range of cellular processes. PPP2R5D is a regulatory B subunit of PP2A and plays an important role in regulating key neuronal and developmental regulation processes such as PI3K/AKT and glycogen synthase kinase 3 beta (GSK3ß)-mediated cell growth, chromatin remodeling, and gene transcriptional regulation. Using whole-exome sequencing (WES), we identified four de novo variants in PPP2R5D in a total of seven unrelated individuals with intellectual disability (ID) and other shared clinical characteristics, including autism spectrum disorder, macrocephaly, hypotonia, seizures, and dysmorphic features. Among the four variants, two have been previously reported and two are novel. All four amino acids are highly conserved among the PP2A subunit family, and all change a negatively charged acidic glutamic acid (E) to a positively charged basic lysine (K) and are predicted to disrupt the PP2A subunit binding and impair the dephosphorylation capacity. Our data provides further support for PPP2R5D as a genetic cause of ID.

Caring for children and adolescents with osteosarcoma: a nursing perspective.

The nurse plays a vital role in caring for patients with osteosarcoma. From the very outset when the disease is explained to the patient and his/her family, the nurse provides comfort and support, as well as enhances and explains the information provided by the physician. All aspects of medical care are addressed, and he/she is frequently the first line of communication when the patient telephones and requests information or wishes to report a problem to the physician. He/She arranges and coordinates appointments to suit the patient's medical, and often social needs to provide comprehensive care with attention to detail. This communication will provide a perspective of the role assumed by the nurse in his/her effort to ensure total care of the patient and the family.

Association between Histoplasma exposure and stroke.

BACKGROUND AND PURPOSE: The rate of cerebrovascular events within the stroke belt, a geographic area defined in the Southeastern United States, exceeds that of the rest of the nation. Despite evaluation of multiple risk factors for this disparity, specific causes for the stroke belt have not been elucidated. More than 45 years ago, the US Public Health Service and US Navy cooperative skin-testing program (1958-1965) documented adolescent exposure to Histoplasma capsulatum. Our purpose was to evaluate the association between exposure to Histoplasma capsulatum and subsequent development of stroke. METHODS: A cross-sectional study of stroke in a cohort of US Navy veterans was designed to assess our hypothesis. Medical records from 23,795 men who participated in the cooperative skin-testing program and who received medical care at Veterans Administration Hospitals and Clinics were reviewed. A logistic regression model was used to estimate the odds ratio of stroke while controlling for multiple covariates. Because of the large number of possible risk factors for stroke, propensity scores were used to reduce bias. RESULTS: The adjusted odds ratio for stroke in veterans exposed to Histoplasma capsulatum during adolescence was 1.34 (95% confidence interval: 1.1-1.6; P = .0033). The increased risk was independent of traditional cerebrovascular event risk factors. Less frequent risk factors (atrial fibrillation, coronary heart disease, rheumatic heart disease, and prosthetic cardiac valvular replacement) were not controlled in this model. CONCLUSION: Exposure to Histoplasma capsulatum during adolescence was associated with an increased risk of stroke.

Outpatient and home chemotherapy with novel local control strategies in desmoplastic small round cell tumor.

Desmoplastic Small Round Cell Tumor (DSRCT) has a very poor prognosis. This report illustrates novel chemotherapy and local control interventions in a 5-year old patient. The patient was treated in the outpatient setting, achieved remission, with excellent quality of life. The patient presented with massive ascites and >1000 abdominal tumors. Neoadjuvant chemotherapy included vincristine (1.5 mg/m(2)), ifosfamide (3 g/m(2)/day x 3), dexrazoxane/doxorubicin (750/75 mg/m(2)), and etoposide (150 mg/m(2)). Continuous hyperthermic peritoneal perfusion (CHPP) with cisplatin (100 mg/m(2)) was given after extensive cytoreductive surgery. This was followed by irinotecan (10 mg/m(2)/day x 5 x 2 weeks) + temozolomide monthly x 2, then abdominal radiation 30 Gy with simultaneous temozolomide (100 mg/m(2)/day x 5). A total of 12 cycles of irinotecan and temozolamide were given. Except for initial chemotherapy, subsequent courses were in the outpatient setting. Focal retroperitoneal relapse at 18 months was treated with IMRT with bevacizumab (5 mg/kg) and 2 perihepatic metastases with radio frequency ablation/cryoablation followed by chronic outpatient maintenance chemotherapy (valproic acid, cyclophosphamide, and rapamycin). Almost 2 years from diagnosis, the patient maintained an excellent quality of life. This is a novel approach to the treatment of children with massive abdomino-pelvic DSRCT.

Outpatient chemotherapy plus radiotherapy in sarcomas: improving cancer control with radiosensitizing agents.

BACKGROUND: Cancer control by radiotherapy (RT) can be improved with concurrent chemotherapy. Outpatient strategies for sarcomas that combine chemotherapy and RT are possible since supportive care and RT techniques have improved. METHODS: The current status of non-anthracycline chemotherapy in combination with radiation for high-risk sarcoma is reviewed. RESULTS: Ifosfamide with mesna and newer activated ifosfamide agents (ZIO-201 and glufosfamide) have high potential to improve sarcoma cancer control. In Ewing's sarcoma and osteosarcoma, high-dose ifosfamide with mesna (2.8 g/m2/day of each x 5 days; mesna day 6) can be safely given to outpatients using continuous infusion. Reducing ifosfamide nephrotoxicity and central nervous system side effects are discussed. Other outpatient radiosensitization regimens include gemcitabine (600-1000 mg/m2/dose IV over 1 hour weekly x 2-3 doses), temozolomide (75 mg/m2/daily x 3-6 weeks), or temozolomide (100 mg/m2/dose daily x 5) + irinotecan (10 mg/m2/dose daily x 5 x 2 weeks). In osteosarcoma with osteoblastic metastases on bone scan, samarium (1 mCi/kg; day 3 of RT) and gemcitabine (600 mg/m2 IV over 1 hour day 9 of RT) is a radiosensitization strategy. Future drugs for radiosensitization include beta-D-glucose targeted activated ifosfamide (glufosfamide) and sapacitabine, an oral nucleoside with in vitro activity against solid tumors including sarcomas. CONCLUSIONS: The potential to treat major causes of sarcoma treatment failure (local recurrence and distant metastases) with concurrent chemotherapy during radiation should be considered in high-grade sarcomas.

Congenital cervical instability in a patient with camptomelic dysplasia.

INTRODUCTION: Camptomelic dysplasia (CD) is a rare autosomal dominant skeletal dysplasia classically characterized by bent bones of the extremities, tracheobronchial narrowing, thoracic kyphoscoliosis, and various degrees of phenotypic sex reversal. Most patients die of complications in infancy, although long-term survivors have been reported. CASE REPORT: We report a case of CD complicated by incomplete ossification of the cervical vertebral pedicles, resulting in congenital cervical instability and kyphosis. Closed reduction was performed, and the patient was fitted with a customized cervical orthosis. FINDING: He subsequently developed a complete spinal cord injury at the kyphotic level. This underscores the grim prognosis associated with neonatal cervical spinal instability.

Novel therapeutic approaches in pediatric and young adult sarcomas.

Novel therapy as part of sarcoma treatment schemas can enhance quality of life and is important in improving outcomes of high-risk sarcomas. Additional chemotherapy and biotherapy options to reduce tumor burden and prevent metastases include intra-arterial chemotherapy in osteosarcoma; intrapleural chemotherapy, aerosol 9-nitrocamptothecin, or protracted irinotecan and temozolomide in Ewing's sarcoma; continuous hyperthermic peritoneal perfusion for malignancy involving the peritoneum, such as desmoplastic small round cell tumor; and ifosfamide with muramyl tripeptide phosphatidyl ethanolamine liposomes in osteosarcoma. These treatments bring improved control of symptoms, including reduction in nausea, mucositis, cardiotoxicity, and central nervous system toxicity. Portable infusion devices have facilitated introduction of outpatient doxorubicin, ifosfamide, and methotrexate regimens and home-infusion irinotecan. Physical approaches to eliminate sarcoma tumors and metastases are critical for durable responses. Novel local control measures include embolization before surgery, radiosensitization, anti-vascular endothelial growth factor therapy during chemo-radiotherapy, proton therapy, samarium, thermal ablation (radiofrequency ablation), and cryoablation.

Cryptic unbalanced translocation t(17;18)(p13.2;q22.3) identified by subtelomeric FISH and defined by array-based comparative genomic hybridization in a patient with mental retardation and dysmorphic features.

Molecular cytogenetics allows the identification of cryptic chromosome rearrangements, which is clinically useful in mentally retarded and/or dysmorphic individuals with normal results from conventional cytogenetics analysis. We report on a 3-year-old girl with mental retardation, growth deficiency, speech delay, and dysmorphic features including hypertelorism, upslanting palpebral fissures, midfacial hypoplasia, and posteriorly rotated ears. The G-banding analysis showed a 46,XX,t(3;8)(q26.2;p21.1)mat karyotype. However, her clinical features were suggestive of the 18q syndrome. Subtelomeric FISH analysis revealed a der(18) translocated material from chromosome 17. Array-based comparative genomic hybridization (array-CGH) with subtelomeric BAC and PAC clones confirmed the abnormality and refined the breakpoints to 18q22.3-qter and 17p13.2-pter (deletion of 8.5 Mb and duplication of 3.9 Mb, respectively). This case demonstrates the diagnostic utility of combining conventional cytogenetics with molecular chromosome analyses for the identification of subtle chromosome abnormalities.

High-dose ifosfamide in relapsed pediatric osteosarcoma: therapeutic effects and renal toxicity.

BACKGROUND: Sixteen pediatric osteosarcoma patients, previously treated with conventional chemotherapy (including ifosfamide (IFX), 9 g/m(2)) were retreated with high-dose ifosfamide (HD-IFX, 14 g/m(2) per course), following relapse or development of a new bone tumor. The objective was to obtain responses and an improved event-free survival (EFS). PROCEDURE: HD-IFX was administered as described by Patel SR: J Clin Oncol 1997;15:2378. Efficacy of treatment was assessed initially after two to four courses. The interval between the courses was 3 to 4 weeks. Provided a response was obtained after two to four courses, treatment was continued for an additional eight courses unless progressive disease or an untoward event, for example, renal failure occurred. Tumor sites were: lung, (10) bone (9), and bone and soft-tissue (1). RESULTS: Response after two to four courses was 62.5%: CR 6 and PR 4. A total of 84 courses were administered to the 16 patients: (range 2-10, median 5.5 per patient). Median interval between courses was 28.5 days (range 15-90). Five patients were disease free at 15+ to 63+ months after induction and maintenance therapy. Fever and neutropenia occurred in 12 courses. Nephrotoxicity was a major toxic event and was characterized by creatinine levels at or above three times the upper limit of normal. It was unpredictable and occurred in four patients: two were reversible. The other two patients developed full-blown renal failure; one was treated with renal dialysis, but both eventually succumbed to osteosarcoma. Our past experience also indicated that two patients treated with IFX (9 g/m(2)/course) developed renal failure: one recovered and the other required a renal transplant. CONCLUSIONS: HD-IFX is effective in patients who have failed conventional chemotherapy including IFX (9 g/m(2)). Improved disease-free survival was achieved in 30% of patients. However, renal failure constitutes an important life-threatening complication and its development is unpredictable.

Identification of genes differentially expressed in association with reduced azole susceptibility in Saccharomyces cerevisiae.

OBJECTIVE: An isolate of S. cerevisiae with reduced susceptibility to fluconazole and itraconazole was developed in the laboratory and used to identify genes that are differentially expressed in association with this phenotype. METHODS: S. cerevisiae strain ATCC 9763 was passaged in increasing concentrations of itraconazole. Itraconazole and fluconazole MICs for the initial isolate (9763S) were 2 and 16 mg/L and for the final isolate (9763I) were 16 and > or =64 mg/L, respectively. Duplicate sets of total RNA from 9763S and 9763I were isolated and hybridized to Affymetrix S98 yeast arrays. To validate results, six differentially expressed genes were further examined by RT-PCR. RESULTS: Of the nearly 6400 open reading frames represented on the array, a total of 116 genes (1.8%) were found to be differentially expressed. Cell wall maintenance genes TIR4 and CCW12, sterol metabolism gene UPC2, small molecule transport genes AUS1 and YHK8, and stress response gene CUP1-1 were expressed at a level at least 2.5-fold higher than the expression level found in 9763S. Eleven energy generation genes, ionic homeostasis genes FRE1, FRE2 and FRE4, and sterol metabolism genes ERG8 and ERG13 were expressed at least 2.5-fold lower than the expression level found in 9763S. CONCLUSIONS: Several genes found to be differentially expressed in this study have been shown previously to be differentially expressed in the fungal response to azole treatment. In addition, the potential role of AUS1 and/or YHK8 as mediators of drug efflux is intriguing and warrants further study.

Voriconazole: a new triazole antifungal agent.

OBJECTIVE: To review the pharmacology, in vitro susceptibility, pharmacokinetics, clinical efficacy, and adverse effects of voriconazole, a triazole antifungal agent. DATA SOURCES: A MEDLINE search, restricted to English language, was conducted from 1990 to June 2002. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2001 and manufacturer information available through the Food and Drug Administration's Web site. DATA EXTRACTION: All published and unpublished trials and abstracts citing voriconazole were selected. DATA SYNTHESIS: Voriconazole has shown in vitro activity against many yeasts and a variety of mold and dermatophyte isolates. Voriconazole can be administered either orally or parenterally. It exhibits good oral bioavailability, wide tissue distribution including distribution into the central nervous system, and hepatic metabolism. Drug interactions occur through inhibition of the CYP2C9, CYP2C19, and CYP3A4 isoenzymes, resulting in alterations in kinetic parameters of either voriconazole or the interacting agent. Efficacy has been illustrated in open, noncomparative studies of aspergillosis in immunocompromised patients. Human case reports describe successful treatment of rare fungal pathogens. The most commonly reported adverse events include visual disturbances and elevations in liver function tests. CONCLUSIONS: Voriconazole is at least as effective as amphotericin B in the treatment of acute invasive aspergillosis in immunocompromised patients. It has similar efficacy as fluconazole in treatment of esophageal candidiasis. Voriconazole did not achieve statistical non-inferiority to liposomal amphotericin B for empirical therapy in patients with neutropenia and persistent fever, diminishing enthusiasm for use in this indication until additional trials are completed. Based on case reports and in vitro efficacy, voriconazole may prove to be a clinically useful agent in the treatment of other fungal disease.

Differential expression of genes encoding immunomodulatory proteins in response to amphotericin B in human mononuclear cells identified by cDNA microarray analysis.

Amphotericin B (AMB) is an antifungal agent that possesses immunomodulatory properties that may contribute to its infusion-related toxicity and activity. It has previously been shown to induce the expression of genes encoding the cytokines interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha and the chemokines IL-8 and macrophage inflammatory protein (MIP)-1 beta in the human monocytic cell line THP-1. In an effort to identify additional AMB-responsive genes, the gene expression profiles of both THP-1 cells and human peripheral blood mononuclear cells (hPBMCs) on exposure to AMB were assessed using cDNA microarray analysis. In addition to genes known to be AMB responsive, we found the genes encoding IL-1 alpha and MIP-1 alpha to be AMB responsive in both THP-1 cells and hPBMCs. Increases in MIP-1 alpha and MIP-1 beta were also observed in the supernatants of hPBMCs exposed to AMB. The expression of several genes in response to AMB was unique to either cell type. Furthermore, variability in gene expression in hPBMCs was observed between donors. These genes and respective gene products may have significance in the infusion-related toxicity and activity of AMB.