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SummaryRoot amputation, extraction of a single tooth, bone loss or severe tooth mobility, and an unclosed wound were significantly associated with increased risk of developing medication-related osteonecrosis of the jaw (MRONJ). We recommend a minimally traumatic extraction technique, removal of any bone edges, and mucosal wound closure as standard procedures in patients receiving bisphosphonates.IntroductionOsteonecrosis of the jaws can occur following tooth extraction in patients receiving bisphosphonate drugs. Various strategies for minimizing the risk of MRONJ have been advanced, but no studies have comprehensively analyzed the efficacy of factors such as primary wound closure, demographics, and drug holidays in reducing its incidence. The purpose of this study was to retrospectively investigate the relationships between these various risk factors after tooth extraction in patients receiving oral bisphosphonate therapy.MethodsRisk factors for MRONJ after tooth extraction were evaluated using univariate and multivariate analysis. All patients were investigated with regard to demographics; type and duration of oral bisphosphonate use; whether they underwent a discontinuation of oral bisphosphonates before tooth extraction (drug holiday), and the duration of such discontinuation; and whether any additional surgical procedures (e.g., incision, removal of bone edges, root amputation) were performed.ResultsWe found that root amputation (OR = 6.64), extraction of a single tooth (OR = 3.70), bone loss or severe tooth mobility (OR = 3.60), and an unclosed wound (OR = 2.51) were significantly associated with increased risk of developing MRONJ.ConclusionsWe recommend a minimally traumatic extraction technique, removal of any bone edges, and mucosal wound closure as standard procedures in patients receiving bisphosphonates. We find no evidence supporting the efficacy of a pre-extraction short-term drug holiday from oral bisphosphonates in reducing the risk of MRONJ.

To gain insight into the mechanism of coordination of stepping in the fore and hind legs of quadrupeds, we examined the kinematics of leg movements and the motor patterns in fore and hind leg flexor muscles in decerebrate walking cats when the two pairs of legs stepped on separate treadmills running at different speeds. When the front treadmill was slowed progressively from 0.6 to 0.3 m/s with the rear treadmill running at 0.6 m/s, the rate of stepping in both the fore and hind legs decreased and a 1:1 stepping ratio was maintained. The decrease in the rate of stepping in the hind legs was due primarily to an increase in the duration of the swing phase. Slowing the speed of the rear treadmill while keeping the front treadmill speed at 0.6 m/s decreased the rate of stepping of the hind legs, but had relatively little influence on the average rate of stepping in the forelegs. In this situation stepping in the fore and hind legs was uncoupled and the time of stepping in one hind leg relative to the ipsilateral foreleg progressively shifted during a walking sequence. Analysis of the timing of electromyographic (EMG) recordings from flexor muscles of the hip and elbow joints yielded insight into the neuronal mechanisms underlying the asymmetry in slowing either the front or rear treadmill. We propose that ipsilateral pattern generating networks are asymmetrically coupled via descending inhibitory pathways and an ascending excitatory pathway. We discuss how the characteristics of these linkages are functionally appropriate for establishing the normal timing of stepping in the hind and forelegs during slow walking.

Background The long-term effect of repetitive trauma by military parachuting on the lumbar spine is not well investigated. Therefore, the purpose of this study was to examine the development of lumbar degenerative changes during a 30-year follow-up in Japanese Ground Self Defense Forces (JGSDF) parachute infantry soldiers with normal lumbar radiographs at entry by comparison with those with non-parachute infantry soldiers. Methods 79 non-parachutists and 65 parachutists were included for radiological examination and questionnaires for low back pain (LBP). All subjects were non-commissioned officers with similar socioeconomic status and life styles. The number of parachuting descent during the 30-year in the parachute group ranged from 208 to 630, with an average of 322. Results The mean age of the subjects was 18.3 ± 0.5 years at entry and 48.5 ± 0.3 years at follow-up. LBP had been experienced by 37% in the non-parachute group and 25% in the parachute group with no significant difference. The nature of their LBP was judged as mild. The prevalence rate of degenerative changes was similar in both groups. Disc space narrowing was detected 37 subjects (47%) in non-parachute group an 23 subjects (35%) in parachute group without significant difference. Vertebral osteophytes were detected in 52 subjects (67%) in non-parachute group and 47 subjects (72%) in parachute group without significant difference. Conclusions This study did not identify any significant differences in the development of lumbar degenerative changes between the parachutists and non-parachutists over a 30-year follow-up, suggesting that military parachuting itself does not accelerate the development of intervertebral disc degeneration. Further studies are needed using large cohorts assessed by MRI as well as plain X-ray.

DNA interstrand crosslinks (ICL) present a major threat to cell viability and genome integrity. In eukaryotic cells, the ICLs have been suggested to be repaired by a complex process involving Xpf/Ercc1-mediated endonucleolytic incision and homologous recombination (HR). However, the entire feature of the ICL tolerating mechanism is still poorly understood. Here we studied chromosome aberrations (CA) and sister chromatid exchanges (SCE) by the use of the crosslinking agent mitomycin C (MMC), in chicken DT40 cells with the HR genes disrupted by targeted replacement. The disruption of the Rad54, Rad51B, Rad51C, Rad51D, Xrcc2 and Xrcc3 genes resulted in a dramatic reduction of spontaneous and MMC-induced SCEs. Interestingly, while HR-deficient cells were hypersensitive to cell killing by MMC, MMC-induced CAs were also suppressed in the HR-deficient cells except for Rad51D-, Xrcc2- and Xrcc3-deficient cells. These observations indicate that DNA double strand breaks (DSB) at stalled replication forks and those arising as repair intermediates present strong signals to cell death but can be tolerated by the HR repair pathway, where Rad54, Rad51B and Rad51C have an initiative role and repair can be completed by their paralogs Rad51D, Xrcc2 and Xrcc3. The impairment of the HR pathway, which otherwise leads to cell death, may be somewhat substituted by an alternative mechanism such as the Mre11/Rad50/Nbs1 pathway, resulting in reduced frequencies of SCEs and CAs.   

Covalent bond describes electron pairing in between a pair of atoms and molecules. The space is partitioned in mutually disjoint regions by using a new concept of the electronic drop region R(D), atmosphere region R(A), and the interface S (Tachibana in J Chem Phys 115:3497-3518, 2001). The covalent bond formation is then characterized by a new concept of the spindle structure. The spindle structure is a geometrical object of a region where principal electronic stress is positive along a line of principal axis of the electronic stress that connects a pair of the R(D)s of atoms and molecules. A new energy density partitioning scheme is obtained using the Rigged quantum electrodynamics (QED). The spindle structure of the stress tensor of chemical bond has been disclosed in the course of the covalent bond formation. The chemical energy density visualization scheme is applied to demonstrate the spindle structures of chemical bonds in H2, C2H6, C2H4 and C2H2 systems. [Figure: see text]. Field theory of the energy density.

In walking cats, the biarticular medial and lateral gastrocnemius (MG-LG) muscles act to produce extension and flexion torques at the ankle and knee, respectively, and they usually display only one burst of activity beginning just before ground contact and ending near the end of the stance phase. Currently, the MG-LG muscles are considered to function primarily to control extension movements around the ankle joint during the stance phase. However, their flexion action at the knee means that they have the capacity to regulate rotations at the knee, but this role has not yet been clearly defined. Following partial denervation of the other muscles that normally act to flex the knee during swing, we observed that the MG-LG muscles, but not the Soleus muscle (a pure ankle extensor), often generated strong bursts of activity during early swing. These bursts were enhanced following mechanical stimulation of the paw, and they were especially prominent when the leg trailed over an object. They were absent when the leg led over an object. During treadmill walking the swing-related bursts in MG and LG had little influence on ankle flexion at the beginning of swing, but they were associated with slowing of ankle flexion when the leg trailed over an object. We hypothesized that the recruitment of these bursts functions to partially compensate for the reduction in knee torque resulting from the denervation of other knee flexors. Consistent with this hypothesis was our finding that the magnitude of the swing-related activity in the MG-LG muscles was linearly correlated to the extent of the knee flexion and to the peak angular velocity of knee flexion, and that the timing of the bursts was similar to that in the denervated muscles prior to denervation. Our findings suggest that an excitatory pathway exists from the flexor half-center of the central pattern-generating network to MG-LG motoneurons, and that this pathway is strongly regulated by central and/or peripheral signals.

Huanglongbing (HLB) was first identified near Araraquara in the central region of São Paulo State (SPS), Brazil, in March 2004. As of November 2009, HLB was present in 242 of the 425 citrus-growing municipalities of SPS. In April 2009, the current total number of symptomatic trees was estimated to be ca. 2.0 million (ca. 0.87%) and 4 million trees had already been removed. The recommended measures for HLB management are based on two phytopathologically sound principles: (i) inoculum reduction by frequent removal of HLB-affected trees and (ii) control of psyllid vector populations by insecticide treatments. The goal of this management strategy is to prevent as many trees as possible from becoming infected with the HLB pathogen. After five or six years of HLB management, several SPS citrus farms have shared their results on HLB control. Here we present data from eighteen farms where the recommended measures have been applied since 2004 or 2005 in SPS, showing that HLB can be controlled. SPS is one of the first regions in the world where preventive control against Asian HLB has been carried out on a large scale under various conditions and found to be successful when the recommended measures were applied rigorously. However, only one-third of SPS citrus trees are under effective HLB-management and they are located on large farms, where HLB management is easier than on small farms. The majority of trees in small and medium-sized groves commonly do not benefit from HLB management. This is the reason that HLB incidence in SPS has increased in spite of HLB management. Many groves in which no HLB management is carried out have high proportions of HLB-affected trees and large populations of HLB-positive psyllid vectors. These groves are the major obstacle to HLB management in SPS. These severely affected groves endanger the very existence of the Brazilian citrus industry. When such groves are within a ca. 4km range from well-man-aged farms, their psyllids invariably invade and contaminate the latter farms. SPS has legal tools, which make possible the removal of contaminating groves, but the laws are not strictly enforced. Costs of HLB management vary considerably, but inspections range from $4 to 17 $US each per ha, and insecticide treatments from about $US 240 to > $1,000 per ha annually, depending on the products used, the means and frequency of application. HLB management as described here is only a short-term solution to keep the citrus industry alive and to buy time for long-term solutions, probably based on engineered citrus genotypes, to become available, hopefully, in five to ten years.

Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease. At least eight complementation groups (FA-A to FA-H) have been identified. Previously, we studied mutations of the FANCA gene, responsible for FA-A, and found pathogenic mutations in 12 of 15 unclassified Japanese FA patients. Here, we further studied an additional 5 FA patients for sequence alterations of the FANCA gene and found pathogenic mutations in 2 of them. We further analyzed mutations of the FANCC and FANCG genes, responsible for FA-C and FA-G, respectively, in the remaining 6 FA patients. Although there was no alterations in the FANCC gene in these 6 patients, two novel mutations of the FANCG gene, causing aberrant RNA splicing, were detected in 2 FA patients. One was a base substitution from G to C of the invariant GT dinucleotides at the splice donor site of intron 3, resulting in the skipping of exon 3, as well as the skipping of exons 3 and 4. The other was a base substitution from C to T in exon 8, creating a nonsense codon (Q356X). This mutation resulted in the exclusion of a sequence of 18 nucleotides containing the mutation from the mRNA, without affecting the splicing potential of either the authentic or the cryptic splice donor site. Collectively, 14 of the 20 unclassified Japanese FA patients belong to the FA-A group, 2 belong to the FA-G group, and none belongs to the FA-C group.

Neonatal thrombocytosis can result from maternal narcotic drug abuse. The case of a male infant is reported who was born to a woman with schizophrenia treated with non-narcotic psychotropic drugs during pregnancy; he developed severe prolonged thrombocytosis. The platelet count reached 1310 × 109/l on day 15. This thrombocytosis persisted for three months. The patient was treated with dipyridamole. A bone marrow aspirate showed normal myeloid and erythroid precursors with an increased number of megakaryocytes. Plasma concentrations of interleukin 6 and thrombopoietin were suppressed. No obvious complications from the thrombocytosis occurred, and the platelet count fell to within the upper limit of normal after 3 months of age. This case indicates that thrombocytosis may occur in infants born to mothers treated with non-narcotic psychopharmaceutical drugs during pregnancy. The thrombocytosis in this case may have been induced by factors other than interleukin 6 or thrombopoietin.