Medication-related osteonecrosis of the jaw after tooth extraction in cancer patients: a multicenter retrospective study.

Root amputation, immunosuppressive therapy, mandibular tooth extraction, pre-existing inflammation, and longer duration of treatment with bone-modifying agents were significantly associated with an increased risk of medication-related osteonecrosis of the jaw. Hopeless teeth should be extracted without drug holiday before the development of inflammation in cancer patients receiving high-dose bone-modifying agents. INTRODUCTION: No studies have comprehensively analyzed the influence of pre-existing inflammation, surgical procedure-related factors such as primary wound closure, demographic factors, and drug holiday on the incidence of medication-related osteonecrosis of the jaw (MRONJ). The purpose of this study was to retrospectively investigate the relationships between these various factors and the development of MRONJ after tooth extraction in cancer patients receiving high-dose bone-modifying agents (BMAs) such as bisphosphonates or denosumab. METHODS: Risk factors for MRONJ after tooth extraction were evaluated with univariate and multivariate analyses. The following parameters were investigated in all patients: demographics, type and duration of BMA use, whether BMA use was discontinued before tooth extraction (drug holiday), the duration of such discontinuation, the presence of pre-existing inflammation, and whether additional surgical procedures (e.g., incision, removal of bone edges, root amputation) were performed. RESULTS: We found that root amputation (OR = 22.62), immunosuppressive therapy (OR = 16.61), extraction of mandibular teeth (OR = 12.14), extraction of teeth with pre-existing inflammation, and longer duration (≥ 8 months) of high-dose BMA (OR = 7.85) were all significantly associated with MRONJ. CONCLUSIONS: Tooth extraction should not necessarily be postponed in cancer patients receiving high-dose BMA. The effectiveness of a short-term drug holiday was not confirmed, as drug holidays had no significant impact on MRONJ incidence. Tooth extraction may be acceptable during high-dose BMA therapy until 8 months after initiation.

B-RAF mutation and accumulated gene methylation in aberrant crypt foci (ACF), sessile serrated adenoma/polyp (SSA/P) and cancer in SSA/P.

BACKGROUND: Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor of colon cancer with microsatellite instability (MSI). However, the developmental mechanism of SSA/P remains unknown. We performed genetic analysis and genome-wide DNA methylation analysis in aberrant crypt foci (ACF), SSA/P, and cancer in SSA/P specimens to show a close association between ACF and the SSA/P-cancer sequence. We also evaluated the prevalence and number of ACF in SSA/P patients. METHODS: ACF in the right-side colon were observed in 36 patients with SSA/Ps alone, 2 with cancers in SSA/P, and 20 normal subjects and biopsied under magnifying endoscopy. B-RAF mutation and MSI were analysed by PCR-restriction fragment length polymorphism (RFLP) and PCR-SSCP, respectively, in 15 ACF, 20 SSA/P, and 2 cancer specimens. DNA methylation array analysis of seven ACF, seven SSA/P, and two cancer in SSA/P specimens was performed using the microarray-based integrated analysis of methylation by isochizomers (MIAMI) method. RESULTS: B-RAF mutations were frequently detected in ACF, SSA/P, and cancer in SSA/P tissues. The number of methylated genes increased significantly in the order of ACF

Sonoelastographic Findings of Carpal Tunnel Injection.

PURPOSE: The objectives of this study were to compare sonoelastographic color findings of the perineural area between carpal tunnel syndrome patients and healthy volunteers, and to analyze elastographic findings in that area before and immediately after intracarpal tunnel injection in carpal tunnel syndrome patients. MATERIALS AND METHODS: We studied both hands of 15 healthy volunteers (7 men, 8 women; mean age: 60.1 years, range: 41 - 88 years) and 72 hands from 70 patients with symptomatic carpal tunnel syndrome (24 men, 46 women; mean age: 54.2 years, range: 24 - 83 years). Sonoelastographic color distribution was assessed in the perineural area between the median nerve and adjacent flexor tendons. The color elastograms were graded using the following system: Grade 1 as red (softest), grade 2 as yellow (soft), grade 3 as green (hard), grade 4 as blue (hardest). The patients were treated with corticosteroid injection and were reassessed with sonoelastography immediately after the injection. RESULTS: The median color grading in the perineural area of carpal tunnel syndrome patients was grade 3 (3.1 ±â€Š0.3, mean ±â€Š95 % Cl), which was stiffer than that of healthy volunteers (grade 1, 1.9 ±â€Š0.4) (p < 0.0001). Immediately after injection, the diffusion of the injected fluid was observed as having a softer appearance (grade 1, 1.4 ±â€Š0.2) (p < 0.0001). CONCLUSION: The perineural area surrounding the median nerve in carpal tunnel syndrome patients was stiffer than that in healthy volunteers. Diffusion of the injected fluid in the carpal tunnel was seen as a softer finding after injection in real time using sonoelastography.

Synovitis of the wrist caused by Mycobacterium florentinum.

Mycobacterium florentinum is a newly identified, rare, slow-growing species of nontuberculous mycobacteria (NTM). Here, we report a case of M. florentinum-induced synovitis of the wrist in an immunocompromised Japanese patient. M. florentinum was identified by sequence analysis of the rpoB, hsp65, and 16S rRNA genes. The M. florentinum strain in this study could not be differentiated from certain M. triplex strains by the hsp65 or 16S rRNA sequences alone, because they occasionally shared more than 99 % sequence identity. The isolated M. florentinum strain was only susceptible to clarithromycin and amikacin. Initially, the patient was treated with clarithromycin, levofloxacin, and ethambutol, and then with clarithromycin, levofloxacin, and rifampicin. To our knowledge, M. florentinum-induced synovitis has not been previously reported. Our results suggest that, in addition to other well-known pathogenic NTM, the recently identified M. florentinum strain should be considered as a possible cause of synovitis. Moreover, we should be cautious when identifying M. florentinum because this strain closely resembles M. triplex in genotype.

Potential probiotic thermophiles isolated from mice after compost ingestion.

AIMS: The oral administration of a compost produced by the fermentation of marine animals with thermophiles confers health benefits for fish and pigs. This study aimed to isolate the beneficial bacteria from this compost that would modulate the physiological conditions of host animals. METHODS AND RESULTS: The compost extract was orally administrated to germ-free mice for 21 days, and thereafter, the culturable bacterial population within the caeca was surveyed. Sequence analyses of the 16S rRNA gene from the two predominant thermophilic isolates revealed organisms that were closely related to Bacillus thermoamylovorans and Bacillus coagulans. These bacteria could grow at 37°C, but more abundantly at 50-55°C, and they were minor components of the original compost extract. When an individual bacterial strain or a mixture of strains was administered to the conventionally maintained mice, their levels of faecal immunoglobulin A, an indicator of the gut immune response, were markedly raised. In addition, their feeding efficiency also changed among the tested mouse groups. CONCLUSIONS: These two kinds of thermophilic bacterial species, isolated from the caeca after compost ingestion to the germ-free mice, are candidate probiotics that could function in the mammalian gut. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed that the compost used in agriculture can contain potential probiotic thermophiles.

Three-dimensional power Doppler transanal ultrasonography, to monitor haemorrhoidal blood flow after Doppler-guided ALTA sclerosing therapy.

AIM: The study aimed to use power Doppler imaging (PDI) transanal ultrasonography to produce three-dimensional power Doppler angiography images of haemorrhoidal tissue and to monitor the effects of Doppler-guided aluminium potassium sulfate and tannic acid (DGALTA) sclerotherapy. METHOD: Ninety-six haemorrhoids in 43 patients were examined using PDI transanal ultrasonography, and DGALTA sclerotherapy was performed from April 2011 to April 2012. DGALTA sclerotherapy was conducted using a four-step injection process with pulse wave Doppler ultrasound under perianal local anaesthesia. RESULTS: A three-dimensional power Doppler angiography image of the blood flow in haemorrhoidal tissue was produced using PDI transanal ultrasonography. The cross-sectional area of blood flow in the haemorrhoidal tissue (PDI area) significantly decreased after DGALTA sclerotherapy. The PDI areas in the preoperative state and 1 and 3 months after treatment were 0.35±0.27, 0.03±0.05 and 0.04±0.05 cm(2) (P<0.0001). CONCLUSION: A three-dimensional power Doppler angiography image of the haemorrhoidal tissue was technically possible and showed blood flow in the haemorrhoidal tissue to be significantly decreased after DGALTA sclerotherapy.

Visualization and hypervascularization of the haemorrhoidal plexus in vivo using power Doppler imaging transanal ultrasonography and three-dimensional power Doppler angiography.

AIM: The purpose of this study was to demonstrate the distribution of haemorrhoidal arteries and the relationship between vascularity and growth of haemorrhoids. METHOD: One-hundred and three patients with haemorrhoids were studied. Using power Doppler imaging (PDI) transanal ultrasound and three-dimensional power Doppler angiography (3D-PDA), the course of the arteries supplying the haemorrhoids was identified. Measurement of the PDI area was made using the cursor to outline the power Doppler signal of the haemorrhoid, approximately 1 cm above the dentate line. RESULTS: The haemorrhoidal arteries were seen as branches of the superior rectal artery and were detected in 75.7, 71.8, 68.0 and 62.1% of the 11, 7, 3 and 1 o'clock positions in the lithotomy position. The median number of haemorrhoidal arteries significantly increased from three to six with progression of the Goligher classification from Grade 1 to Grade 4 (P < 0.0001). The PDI areas in Grades 1, 2, 3 and 4 were 0.04 ± 0.03, 0.18 ± 0.07, 0.38 ± 0.18 and 0.96 ± 0.32 cm(2) (P < 0.05). CONCLUSION: The distribution of haemorrhoidal arteries varies widely in both number and position. Using PDI transanal ultrasonography and 3D-PDA it was possible to visualize the haemorrhoid plexus and the course of the haemorrhoidal artery in vivo.

Granular flow experiment using artificial gravity generator at International Space Station.

Studying the gravity-dependent characteristics of regolith, fine-grained granular media covering extra-terrestrial bodies is essential for the reliable design and analysis of landers and rovers for space exploration. In this study, we propose an experimental approach to examine a granular flow under stable artificial gravity conditions for a long duration generated by a centrifuge at the International Space Station. We also perform a discrete element simulation of the granular flow in both artificial and natural gravity environments. The simulation results verify that the granular flows in artificial and natural gravity are consistent. Further, regression analysis of the experimental results reveals that the mass flow rate of granular flow quantitatively follows a well-known physics-based law with some deviations under low-gravity conditions, implying that the bulk density of the granular media decreases with gravity. This insight also indicates that the bulk density considered in simulation studies of space probes under low-gravity conditions needs to be tuned for their reliable design and analysis.

Dataset of night-time emissions of the Earth in the near UV range (290-430 nm), with 6.3 km resolution in the latitude range -51.6

The data presented in this article are related to the research paper entitled "Observation of night-time emissions of the Earth in the near UV range from the International Space Station with the Mini-EUSO detector" (Remote Sensing of Environment, Volume 284, January 2023, 113336, https://doi.org/10.1016/j.rse.2022.113336). The data have been acquired with the Mini-EUSO detector, an UV telescope operating in the range 290-430 nm and located inside the International Space Station. The detector was launched in August 2019, and it has started operations from the nadir-facing UV-transparent window in the Russian Zvezda module in October 2019. The data presented here refer to 32 sessions acquired between 2019-11-19 and 2021-05-06. The instrument consists of a Fresnel-lens optical system and a focal surface composed of 36 multi-anode photomultiplier tubes, each with 64 channels, for a total of 2304 channels with single photon counting sensitivity. The telescope, with a square field-of-view of 44°, has a spatial resolution on the Earth surface of 6.3 km and saves triggered transient phenomena with a temporal resolution of 2.5 µs and 320 µs. The telescope also operates in continuous acquisition at a 40.96 ms scale. In this article, large-area night-time UV maps obtained processing the 40.96 ms data, taking averages over regions of some specific geographical areas (e.g., Europe, North America) and over the entire globe, are presented. Data are binned into 0.1° × 0.1° or 0.05° × 0.05° cells (depending on the scale of the map) over the Earth's surface. Raw data are made available in the form of tables (latitude, longitude, counts) and .kmz files (containing the .png images). These are - to the best of our knowledge - the highest sensitivity data in this wavelength range and can be of use to various disciplines.

Prevention of excessive collagen accumulation by human intravenous immunoglobulin treatment in a murine model of bleomycin-induced scleroderma.

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrotic changes in skin and other organs involving excessive collagen deposition. Here we investigated the effect of intravenous immunoglobulin (IVIG) on fibrosis in a murine model of bleomycin (BLM)-induced scleroderma. Scleroderma was induced in C3H/He J mice by subcutaneous BLM injections daily for 35 days. The collagen content in skin samples from the BLM-injected group (6·30 ± 0·11 mg/g tissue) was significantly higher than the PBS group (5·80 ± 0·10 mg/g tissue), and corresponded with dermal thickening at the injection site. In contrast, mice treated with IVIG for 5 consecutive days after initiating BLM injection showed lesser collagen content significantly (IVIG group, 5·61 ± 0·09 mg/g tissue; BLM vs. IVIG). In order to investigate the cellular and protein characteristics in the early stage of the model, the skin samples were obtained 7 days after the onset of experiment. Macrophage infiltration to the dermis, monocyte chemoattractant protein (MCP-1)-positive cells, and increased TGF-ß1 mRNA expression were also observed in the BLM group. IVIG inhibited these early fibrogenic changes; MCP-1 expression was significantly lesser for the IVIG group (1·52 ± 0·19 pg/mg tissue) than for the BLM group (2·49 ± 0·26 pg/mg tissue). In contrast, TGF-ß1 mRNA expression was significantly inhibited by IVIG. These results suggest that IVIG treatment may inhibit macrophage recruitment to fibrotic sites by down regulating MCP-1 and TGF-ß production, and thus could be a potential drug for managing fibrotic disorders such as SSc.

Androgen deprivation-induced elevated nuclear SIRT1 promotes prostate tumor cell survival by reactivation of AR signaling.

The NAD+-dependent deacetylase, Sirtuin 1 (SIRT1) is involved in prostate cancer pathogenesis. However, the actual contribution is unclear as some reports propose a protective role while others suggest it is harmful. We provide evidence for a contextual role for SIRT1 in prostate cancer. Our data show that (i) mice orthotopically implanted with SIRT1-silenced LNCaP cells produced smaller tumors; (ii) SIRT1 suppression mimicked AR inhibitory effects in hormone responsive LNCaP cells; and (iii) caused significant reduction in gene signatures associated with E2F and MYC targets in AR-null PC-3 and E2F and mTORC1 signaling in castrate-resistant ARv7 positive 22Rv1 cells. Our findings further show increased nuclear SIRT1 (nSIRT1) protein under androgen-depleted relative to androgen-replete conditions in prostate cancer cell lines. Silencing SIRT1 resulted in decreased recruitment of AR to PSA enhancer selectively under androgen-deprivation conditions. Prostate cancer outcome data show that patients with higher levels of nSIRT1 progress to advanced disease relative to patients with low nSIRT1 levels. Collectively, we demonstrate that lowering SIRT1 levels potentially provides new avenues to effectively prevent prostate cancer recurrence.

Collisional formation of top-shaped asteroids and implications for the origins of Ryugu and Bennu.

Asteroid shapes and hydration levels can serve as tracers of their history and origin. For instance, the asteroids (162173) Ryugu and (101955) Bennu have an oblate spheroidal shape with a pronounced equator, but contain different surface hydration levels. Here we show, through numerical simulations of large asteroid disruptions, that oblate spheroids, some of which have a pronounced equator defining a spinning top shape, can form directly through gravitational reaccumulation. We further show that rubble piles formed in a single disruption can have similar porosities but variable degrees of hydration. The direct formation of top shapes from single disruption alone can explain the relatively old crater-retention ages of the equatorial features of Ryugu and Bennu. Two separate parent-body disruptions are not necessarily required to explain their different hydration levels.

Sample collection from asteroid (162173) Ryugu by Hayabusa2: Implications for surface evolution.

The near-Earth asteroid (162173) Ryugu is thought to be a primitive carbonaceous object that contains hydrated minerals and organic molecules. We report sample collection from Ryugu's surface by the Hayabusa2 spacecraft on 21 February 2019. Touchdown images and global observations of surface colors are used to investigate the stratigraphy of the surface around the sample location and across Ryugu. Latitudinal color variations suggest the reddening of exposed surface material by solar heating and/or space weathering. Immediately after touchdown, Hayabusa2's thrusters disturbed dark, fine grains that originate from the redder materials. The stratigraphic relationship between identified craters and the redder material indicates that surface reddening occurred over a short period of time. We suggest that Ryugu previously experienced an orbital excursion near the Sun.

Hayabusa2 arrives at the carbonaceous asteroid 162173 Ryugu-A spinning top-shaped rubble pile.

The Hayabusa2 spacecraft arrived at the near-Earth carbonaceous asteroid 162173 Ryugu in 2018. We present Hayabusa2 observations of Ryugu's shape, mass, and geomorphology. Ryugu has an oblate "spinning top" shape, with a prominent circular equatorial ridge. Its bulk density, 1.19 ± 0.02 grams per cubic centimeter, indicates a high-porosity (>50%) interior. Large surface boulders suggest a rubble-pile structure. Surface slope analysis shows Ryugu's shape may have been produced from having once spun at twice the current rate. Coupled with the observed global material homogeneity, this suggests that Ryugu was reshaped by centrifugally induced deformation during a period of rapid rotation. From these remote-sensing investigations, we identified a suitable sample collection site on the equatorial ridge.

The geomorphology, color, and thermal properties of Ryugu: Implications for parent-body processes.

The near-Earth carbonaceous asteroid 162173 Ryugu is thought to have been produced from a parent body that contained water ice and organic molecules. The Hayabusa2 spacecraft has obtained global multicolor images of Ryugu. Geomorphological features present include a circum-equatorial ridge, east-west dichotomy, high boulder abundances across the entire surface, and impact craters. Age estimates from the craters indicate a resurfacing age of [Formula: see text] years for the top 1-meter layer. Ryugu is among the darkest known bodies in the Solar System. The high abundance and spectral properties of boulders are consistent with moderately dehydrated materials, analogous to thermally metamorphosed meteorites found on Earth. The general uniformity in color across Ryugu's surface supports partial dehydration due to internal heating of the asteroid's parent body.

Treatment modalities and risk factors associated with refractory neurosensory disturbances of the inferior alveolar nerve following oral surgery: a multicentre retrospective study.

Little research has been conducted into hypoesthesia, and no studies have elucidated the risk factors for refractory hypoesthesia and compared treatment modalities. The purpose of this multicentre retrospective cohort study was to investigate the relationships between various risk factors, treatment modalities, and refractory hypoesthesia. Risk factors for refractory hypoesthesia after oral surgery were evaluated using univariate and multivariate analysis. To minimize the selection bias associated with a retrospective data analysis, a propensity score analysis was performed between the medication and non-medication groups (65 sites in each group). Moderate or severe hypoesthesia (odds ratio 13.42) and no or late administration of ATP/vitamin B12 (odds ratio 2.28) were significantly associated with refractory hypoesthesia. In the propensity score analysis, the incidence rate of refractory hypoesthesia in the medication group was lower than that in the non-medication group (P<0.001). This study demonstrated the multivariate relationships between various risk factors, treatment modalities, and refractory hypoesthesia. Moderate or severe hypoesthesia and no or late administration of ATP/vitamin B12 were significantly associated with refractory hypoesthesia. Therefore, clinicians should consider these risk factors and initiate early oral administration of ATP/vitamin B12 in cases of hypoesthesia.

Genetic diversity of Legionella pneumophila inferred from rpoB and dotA sequences.

This study characterised the population structure of Legionella pneumophila by comparing the rpoB (300-bp) and dotA (360-bp) sequences of 267 isolates (18 reference strains, 149 Korean isolates and 100 Japanese isolates). In addition to the six clonal subgroups established previously, four subgroups, P-V to P-VIII, were identified. Subgroupings based on rpoB and dotA sequences were found to correlate with the source of the isolates, and this data may be useful for future epidemiological studies. Fourteen (five Korean and nine Japanese) isolates showed incongruent subgroupings in the rpoB and dotA trees, suggesting that genetic exchange among subgroups, and even among subspecies, may occur frequently in nature.

Prognostic value of nuclear DNA content and expression of the ras oncogene product in lung cancer.

We evaluated the prognostic significance of nuclear DNA content by flow cytometry and ras oncogene expression in paraffin-embedded sections of tumors obtained surgically from 112 non-small cell lung cancer patients. Sixty-five (77%) of the 84 tumors had DNA aneuploid patterns that were statistically higher in adenocarcinoma than in squamous cell carcinoma. Of the 91 patients analyzed immunohistochemically using anti-ras Mr 21,000 protein (p21) monoclonal antibody rp-35, positive reactions (weak and strong) were observed in 56% of squamous cell carcinomas and 68% of adenocarcinomas. A better 5-yr survival rate was observed in the DNA diploid group (61%) than in the DNA aneuploid group (35%) (P less than 0.01). Patients with p21-negative tumors survived significantly longer (5-yr survival rate of 64%) than did those with p21-weak tumors (38%, P less than 0.05) or those with p21-strong tumors (12%, P less than 0.01). Cox's multivariate analysis showed that DNA ploidy, ras p21 expression, and the stage of the disease were significant prognostic factors for survival. However, the DNA content was not a major independent prognostic factor in adenocarcinoma. The intensity of ras p21 expression was not correlated with nuclear DNA content. These results suggest that DNA content or enhanced ras p21 expression may be different biological markers indicating the malignant potential of lung tumors.