Loss of protein phosphatase 2A regulatory subunit B56δ promotes spontaneous tumorigenesis in vivo.

Protein Phosphatase 2A (PP2A) enzymes counteract diverse kinase-driven oncogenic pathways and their function is frequently impaired in cancer. PP2A inhibition is indispensable for full transformation of human cells, but whether loss of PP2A is sufficient for tumorigenesis in vivo has remained elusive. Here, we describe spontaneous tumor development in knockout mice for Ppp2r5d, encoding the PP2A regulatory B56δ subunit. Several primary tumors were observed, most commonly, hematologic malignancies and hepatocellular carcinomas (HCCs). Targeted immunoblot and immunohistochemistry analysis of the HCCs revealed heterogeneous activation of diverse oncogenic pathways known to be suppressed by PP2A-B56. RNA sequencing analysis unveiled, however, a common role for oncogenic c-Myc activation in the HCCs, independently underscored by c-Myc Ser62 hyperphosphorylation. Upstream of c-Myc, GSK-3ß Ser9 hyperphosphorylation occurred both in the HCCs and non-cancerous B56δ-null livers. Thus, uncontrolled c-Myc activity due to B56δ-driven GSK-3ß inactivation is the likely tumor predisposing factor. Our data provide the first compelling mouse genetics evidence sustaining the tumor suppressive activity of a single PP2A holoenzyme, constituting the final missing incentive for full clinical development of PP2A as cancer biomarker and therapy target.

Telemedicine and orthopaedic care. A review of 2 years of experience.

The objective of this study was to study the delivery of orthopaedic care via a telemedicine network. This study is a descriptive analysis of orthopaedic teleconsultations done during a 2-year period by three orthopaedic surgeons. Four hundred ten teleconsultations were done during the study period from February 1, 1995, to December 31, 1996. Orthopaedic surgeons engaged in 91 teleconsultations (22% of all teleconsultations). Reasons for orthopaedic teleconsultations were: evaluation and treatment of fracture care (39 cases; 43%); evaluation and treatment of ligamentous injury, joint swelling and infection (32 cases; 35%); postoperative evaluation (16 cases; 18%); and evaluation and treatment of dislocations (four cases; 4%). Sixty-two (68%) of the patients remained in the rural community. Twenty-one (23%) of the orthopaedic teleconsultations were classified as emergent (done immediately). Thirty-five (38%) were urgent (done within 1 to 2 hours of provider request), and 35 (38%) were scheduled. The mean duration of time for teleconsultations was 12.8 minutes. Eighty-seven (96%) of the teleconsultations occurred Monday through Friday. Outcome data were collected on all patients involved in teleconsultations. No adverse patient outcomes occurred. This study suggests telemedicine may be an avenue for the delivery of orthopaedic care to patients residing in areas where orthopaedic specialists are not available.

Emergency physicians' roles in a clinical telemedicine network.

STUDY OBJECTIVE: To study the roles emergency physicians have in a clinical telemedicine network. METHODS: A descriptive analysis of telemedicine consultations conducted by emergency physicians at 1 year of operation of a private clinical telemedicine program. RESULTS: From February 1, 1995, to February 1, 1996, 190 clinical telemedicine consultations were completed. Emergency medicine constituted the most common specialty consulted, accounting for 45 (24%) of the consultations. All consultations were one-time transmissions and interactions. They ranked as follows: trauma or orthopedic care, 33 (73%); adult medical problems, 6 (13%); and pediatric medical problems, 6 (13%). Of the emergency medicine teleconsultations, 39 (87%) were categorized as emergency (completed immediately). Of the emergency medicine consultations completed, 24 (53%) patients remained in the rural community, and 21 (47%) were transferred to the tertiary care facility for additional care. The primary peripheral used for emergency medicine teleconsultations was a one-chip document camera. Forty-three (96%) of the emergency medicine teleconsultations involved radiograph interpretations. The most common radiographs reviewed were of the arm, 14 (33%); leg, 10 (23%); and cervical spine, 7 (16%). There was one minor radiograph interpretation discrepancy. Of the emergency medicine teleconsultations, 65% occurred between 7 PM and 8 AM. Of emergency medicine teleconsultations, 24% were completed on Saturdays and Sundays, with 26% of consultations being completed on Fridays. All emergency physicians involved in telemedicine consultations were surveyed concurrently for satisfaction, future use, and recommendations for improvement. CONCLUSION: The technology afforded by telemedicine allows emergency physicians to participate in telemedicine consultations. Emergency physicians should consider using clinical telemedicine in their practice.

Telemedicine in trauma care: description of 100 trauma teleconsults.

OBJECTIVE: To study the role of telemedicine in the delivery of trauma care to rural providers on a telemedicine network. METHODS: A descriptive analysis of 100 trauma teleconsults over a private telemedicine network from February 1, 1995, through July 31, 1996. RESULTS: Of 354 clinical teleconsults during the study period, 100 (28%) concerned trauma. The largest number of trauma teleconsults (54) were provided by orthopedic surgeons. Emergency physicians provided 33 teleconsults, radiologists 8, and neurosurgeons 5. The most common reasons for trauma teleconsults (94%) were diagnosis and treatment of extremity and pelvic injuries. The document camera was used for all teleconsults, primarily to transmit radiographs. The mean age of the patients was 32.3 years. Sixty-one of the teleconsults were categorized as urgent, 32 were emergency, and 7 were scheduled. The mean duration of the emergency teleconsults was 4.3 minutes, and the overall mean duration of all teleconsults was 8.6 minutes. Ninety of the trauma teleconsults occurred during regular week days, Monday through Friday. Radiologists reviewed all hardcopy radiographs and computed tomography films, and hard-copy interpretations were compared with interpretations at the time of the teleconsult. No significant discrepancies between the two modes of interpretation were noted. Of the 100 patients involved in trauma teleconsults, 68 stayed in the rural community. No significant adverse outcomes were observed among patients involved in teleconsults. CONCLUSION: This analysis confirms the clinical effectiveness of telemedicine technology in the evaluation and treatment of extremity and pelvic injuries.