Latent membrane protein 1 of Epstein-Barr virus coordinately regulates proliferation with control of apoptosis

Latent membrane protein 1 (LMP1), an oncoprotein encoded by Epstein-Barr virus (EBV), is an integral membrane protein, which acts like a constitutively active receptor. LMP1 is critical for some facet of EBV's induction and maintenance of proliferation of infected B cells. It, in part, mimics signaling by the CD40 receptor and has been implicated in regulating proliferation, survival, or both properties of EBV-infected cells. We established a conditional LMP1 allele in the context of the intact EBV genome to define the immediate-early cellular target genes regulated by LMP1 in order to assess its contributions to infected human B cells. The functional analysis of this conditional system indicated that LMP1 specifically induces mitogenic B-cell activation through c-myc and Jun/AP1 family members and confirms its direct role in upregulating expression of multiple genes with opposing activities involved in cell survival. LMP1's signals were found to be essential for the G1/S transition in human B cells; cells lacking LMP1's signals are cell cycle arrested and survive quiescently. LMP1's activities are therefore not required to maintain survival in nonproliferating cells. LMP1 does induce both pro- and antiapoptotic genes whose balance seems to permit survival during LMP1's induction and maintenance of proliferation.     

The course and distribution of the inferior alveolar nerve in the edentulous mandible

The authors undertook the study to determine the pattern of intrabony distribution of the branches of the inferior alveolar nerve (IAN) in the edentulous mandible. One hundred seven human cadaveric mandibles were microdissected from their buccal aspect. In each case the height and distribution of the IAN was classified. The authors found that the IAN was located in the lower half of the mandible in 73% of males and 70% of females. The most common branching pattern observed was a single nerve trunk with a series of simple branches directed at the superior border of the mandible (59.6% males, 52% females). The second most common pattern was that of a small nerve plexus in the molar region (21.1% males, 26% females). The results showed that the pattern of distribution does not significantly differ between the sexes, between sides of the jaw, or with age.     

Catch-up growth up to ten years of age in children born very preterm or with very low birth weight

Background  

Improved survival due to advances in neonatal care has brought issues such as postnatal growth and development more to the focus of our attention. Most studies report stunting in children born very preterm and/or small for gestational age. In this article we study the growth pattern of these children and aim to identify factors associated with postnatal catch-up growth.     

Weighing evidence: quantitative measures of the importance of bitemark evidence

Quantitative measures of the importance of evidence such as the "likelihood ratio" have become increasingly popular in the courtroom. These measures have been used by expert witnesses formally to describe their certainty about a piece of evidence. These measures are commonly interpreted as the amount by which the evidence should revise the opinion of guilt, and thereby summarize the importance of a particular piece of evidence. Unlike DNA evidence, quantitative measures have not been widely used by forensic dentists to describe their certainty when testifying about bitemark evidence. There is, however, no inherent reason why they should not be used to evaluate bitemarks. The purpose of this paper is to describe the likelihood ratio as it might be applied to bitemark evidence. We use a simple bitemark example to define the likelihood ratio, its application, and interpretation. In particular we describe how the jury interprets the likelihood ratio from a Bayesian perspective when evaluating the impact of the evidence on the odds that the accused is guilty. We describe how the dentist would calculate the likelihood ratio based on frequentist interpretations. We also illustrate some of the limitations of the likelihood ratio, and show how those limitations apply to bitemark evidence. We conclude that the quality of bitemark evidence cannot be adequately summarized by the likelihood ratio, and argue that its application in this setting may be more misleading than helpful.     

Fracture risks for women in long-term care: high prevalence of calcaneal osteoporosis and hypovitaminosis D

STUDY OBJECTIVES: To determine the prevalence of osteoporosis as assessed by peripheral bone mineral density (BMD) in women living in a nursing home, to determine how many women with low BMD had received a diagnosis of osteoporosis, to assess the prevalence of vitamin D deficiency, and to seek reasons for vitamin D deficiency. DESIGN: Measurement of calcaneal BMD and serum 25-hydroxyvitamin D. SETTING: Skilled nursing facility. PATIENTS: Forty-nine women aged 68-100 years. MEASUREMENTS AND MAIN RESULTS: Bilateral calcaneal BMD was measured by dual-energy x-ray absorptiometry and serum 25-hydroxyvitamin D by radioimmunoassay. Medical records were reviewed to assess osteoporosis risk factors, previous documentation of osteoporosis or malabsorption, and supplemental vitamin D intake. Fifty-nine percent of the 39 women with calcaneal BMD measurements (95% confidence interval [CI] 44-74%) exhibited calcaneal osteoporosis (T score < -2.5). Sixty percent (95% CI 46-74%) had 25-hydroxyvitamin D levels of 20 ng/ml or less, which is associated with secondary hyperparathyroidism; only 4% of women had levels above 30 ng/ml, recently recommended as optimal. Vitamin D status was suboptimal even in most women taking multivitamins. Osteoporosis was documented in the records of 17% of 23 women with calcaneal osteoporosis. CONCLUSION: Osteoporosis was prevalent but poorly documented in women living in the nursing home. Peripheral BMD measurements have the potential to improve the recognition and management of osteoporosis in women in long-term care facilities. The high prevalence of vitamin D deficiency, even in those taking multivitamins, indicates that practical new approaches for vitamin D repletion in this population are urgently needed.     

Prevention of recurrence and prolonged survival in primary central nervous system lymphoma (PCNSL) patients treated with adjuvant high-dose methylprednisolone

Five patients at risk for primary central nervous system lymphoma (PCNSL) recurrence were treated with high-dose methylprednisolone (HDMP) to prevent 'trafficking' of malignant lymphocytes into the central nervous system (CNS). HDMP was chosen because of its ability to stabilize the 'blood brain barrier (BBB)'. Three men with newly diagnosed PCNSL, ages 62, 76 and 78y, whose survival was projected to be 6.6 months, began treatment after achieving complete response (CR) to initial radiation therapy alone and survived 27, 37 and 59 months after treatment. In none was death from recurrent disease in CNS but one patient did die of systemic non-Hodgkin's lymphoma (NHL) five years after PCNSL diagnosis. A 20 y old man was treated with HDMP after successful combined modality therapy and is alive 75+ months after initial diagnosis without evidence of disease recurrence. A 34 y old man relapsed after combined modality initial treatment and failed to respond to HDMP when treatment was begun after unsuccessful salvage therapy; he died of disease 12 months after initial diagnosis. There were no treatment complications. The promising results in this pilot study from the basis for a North Central Cancer Treatment Group (NCCTG) 96-73-51, a Phase 2 clinical trial of brain radiotherapy and HDMP for PCNSL patients 70y of age and older, a group of patients at high risk for toxicity from intensive combined modality therapy.