Predictors of the Effects of Flow Diversion in Very Large and Giant Aneurysms.

BACKGROUND AND PURPOSE: The treatment paradigm for very large and giant aneurysms has recently changed to flow diversion, in light of the results of the Pipeline for Uncoilable or Failed Aneurysms trial. However, the effects of flow diversion were definitely unknown. We explored this topic and identified the predictors of such effects. MATERIALS AND METHODS: We retrospectively reviewed 51 patients with unruptured aneurysms admitted to our institution for flow diversion between February 2014 and August 2019. Patients were categorized into an effect group (no filling or remnant entry) and a no-effect group (subtotal or total filling). We evaluated the aneurysm size and shape, incorporation vessel, parent artery stenosis and curvature, stagnation of contrast medium within the aneurysm, use of balloon angioplasty, and intra-aneurysm thrombus as potential predictors of the effects of flow diversion. RESULTS: The effect group comprised 34 patients (66.7%, 34/51; no filling, 35.3%, 18/51; and remnant entry, 31.4%, 16/51). The no-effect group comprised 17 patients (33.3%, 17/51; subtotal filling, 29.4%, 15/51; and total filling, 3.9%, 2/51). An incorporation vessel and balloon angioplasty were independent risk factors for the no-effect group in multivariate logistic regression analyses (OR = 0.13 and 0.05; 95% confidence intervals, 0.02-0.62 and 0.00-0.32; P values, .021 and .004, respectively). CONCLUSIONS: Flow diversion is effective for very large and giant aneurysms, but the outcomes require further improvement. The results of this study show that an incorporated vessel and excessive balloon angioplasty might compromise flow diversion. This finding can help improve the outcomes of flow diversion.

Intraprocedural Flat Panel Detector Rotational Angiography and an Image Fusion Technique for Delivery of a Microcatheter into the Targeted Shunt Pouch of a Dural Arteriovenous Fistula.

The accurate and safe delivery of a microcatheter to a targeted shunt pouch is essential for successful transvenous embolization of intracranial dural arteriovenous fistulas. However, complex anatomy and variations in head and neck veins and occluded sinuses can hinder intraprocedural microcatheter delivery. In this study, we introduce an intraprocedural flat panel detector rotational angiography and image fusion technique to aid precise navigation inside the veins and proper placement of the microcatheter in the targeted shunt pouch.

Global, Regional, and National Levels and Trends in Burden of Oral Conditions from 1990 to 2017: A Systematic Analysis for the Global Burden of Disease 2017 Study.

Government and nongovernmental organizations need national and global estimates on the descriptive epidemiology of common oral conditions for policy planning and evaluation. The aim of this component of the Global Burden of Disease study was to produce estimates on prevalence, incidence, and years lived with disability for oral conditions from 1990 to 2017 by sex, age, and countries. In addition, this study reports the global socioeconomic pattern in burden of oral conditions by the standard World Bank classification of economies as well as the Global Burden of Disease Socio-demographic Index. The findings show that oral conditions remain a substantial population health challenge. Globally, there were 3.5 billion cases (95% uncertainty interval [95% UI], 3.2 to 3.7 billion) of oral conditions, of which 2.3 billion (95% UI, 2.1 to 2.5 billion) had untreated caries in permanent teeth, 796 million (95% UI, 671 to 930 million) had severe periodontitis, 532 million (95% UI, 443 to 622 million) had untreated caries in deciduous teeth, 267 million (95% UI, 235 to 300 million) had total tooth loss, and 139 million (95% UI, 133 to 146 million) had other oral conditions in 2017. Several patterns emerged when the World Bank's classification of economies and the Socio-demographic Index were used as indicators of economic development. In general, more economically developed countries have the lowest burden of untreated dental caries and severe periodontitis and the highest burden of total tooth loss. The findings offer an opportunity for policy makers to identify successful oral health strategies and strengthen them; introduce and monitor different approaches where oral diseases are increasing; plan integration of oral health in the agenda for prevention of noncommunicable diseases; and estimate the cost of providing universal coverage for dental care.

The Fate of Unruptured Intracranial Vertebrobasilar Dissecting Aneurysm with Brain Stem Compression According to Different Treatment Modalities.

BACKGROUND AND PURPOSE: Unruptured intracranial vertebrobasilar dissecting aneurysms with brain stem compression are difficult to treat. In the present study, the clinical and radiologic outcomes of unruptured intracranial vertebrobasilar dissecting aneurysms with brain stem compression based on different treatment modalities were evaluated. MATERIALS AND METHODS: This study included 28 patients with unruptured intracranial vertebrobasilar dissecting aneurysms with brain stem compression treated from January 2009 to December 2017. Treatment methods were observation (n = 6), stent-assisted coil embolization (n = 9), parent artery occlusion (n = 6), and flow diversion (n = 7). The data of baseline characteristics, change of aneurysm size, retreatment rate, stroke occurrence, and alteration of the mRS score were obtained from retrospective chart review. RESULTS: The initial size of dissecting aneurysms was largest in the flow diversion group (22.5 ± 7.7 mm), followed by parent artery occlusion (20.3 ± 8.4 mm), stent-assisted coil embolization (11.7 ± 2.2 mm), and observation (17.8 ± 5.5 mm; P = .01) groups. The reduction rate of aneurysm size was highest in the parent artery occlusion group (26.7 ± 32.1%), followed by flow diversion (14.1% ± 28.7%), stent-assisted coil embolization (-17.9 ± 30.3%), and observation (-31.5 ± 30.8%; P = .007) groups. Additional treatment was needed in the observation (4/6, 66.7%) and stent-assisted coil embolization (3/9, 33.3%; P = .017) groups. Improvement of the mRS score on follow-up was observed in the flow diversion (6/7, 85.7%) and parent artery occlusion (4/6, 66.7%) groups but not in the stent-assisted coil embolization and observation groups. A worsened mRS score was most common in the observation group (4/6, 66.7%), followed by stent-assisted coil embolization (3/9, 33.3%), parent artery occlusion (2/6, 33.3%), and flow diversion (0/7, 0%) groups. CONCLUSIONS: When treating intracranial vertebrobasilar dissecting aneurysms with brain stem compression, parent artery occlusion and flow diversion should be considered to reduce aneurysm size and improve the mRS score.

Associations between serotonin transporter gene (SLC6A4) methylation and clinical characteristics and cortical thickness in children with ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Additionally, environmental factors such as perinatal stress and early adversities contribute to the occurrence and severity of ADHD. Recently, DNA methylation has emerged as a mechanism that potentially mediates gene-environmental interaction effects in the aetiology and phenomenology of psychiatric disorders. Here, we investigated whether serotonin transporter gene (SLC6A4) methylation patterns were associated with clinical characteristics and regional cortical thickness in children with ADHD. METHOD: In 102 children with ADHD (age 6-15 years), the methylation status of the SLC6A4 promoter was measured. Brain magnetic resonance imaging was obtained and ADHD symptoms were evaluated. RESULTS: A higher methylation status of the SLC6A4 promoter was significantly associated with worse clinical presentations (more hyperactive-impulsive symptoms and more commission errors). Additionally, a negative correlation was observed between SLC6A4 methylation levels and cortical thickness values in the right occipito-temporal regions. CONCLUSIONS: Our results suggest that the SLC6A4 methylation status may be associated with certain symptoms of ADHD, such as behavioural disinhibition, and related brain changes. Future studies that use a larger sample size and a control group are required to corroborate these results.

Association between lumbar discectomy and subsequent cervical discectomy.

BACKGROUND: Lumbar discectomy (LD) is one of the most common spinal surgical procedures. However, the remote effect of the cervical spine has seldom been discussed. The comparative incidence of cervical discectomy with or without a previous LD is an essential feature in predicting this effect. METHODS: A cohort comparative study was conducted from the National Health Research Institute, Taiwan, over the period from 1996 to 2010. Patients who received LDs and patients who did not receive LDs in the same period were randomly selected to serve as samples for comparison. A total of 14 480 patients who did not undergo LD surgery and 3620 patients who received LDs were enrolled in this study. The incidence rates of discectomy-cervical in both groups were calculated from the follow-up period until the end of 2010. The baseline comorbidity history was determined for each patient. Comorbidities included facture and osteoporosis. RESULTS: During the follow-up period, the overall incidence rate of CD was significantly higher in patients who were treated with LD than in those who were not (24.7 vs. 2.73 per 10 000 person years). The risk of CD in the LD-treated cohort was ∼9-fold greater than that of the non-LD-treated cohort (HRs = 8.58, 95% CI = 5.38-13.7). CONCLUSION: Patients who have undergone LDs are at A greater risk of subsequent CDs, an increased risk that is evident in all patients regardless of demographics or the presence of fracture or osteoporosis.

Can bioadhesive nanoparticles allow for more effective particle uptake from the small intestine?

There has been increasing interest in developing bioadhesive nanoparticles due to their great potential as carriers for therapeutics in oral drug delivery systems. Despite decades of research, such a system still has not been successfully implemented. This paper demonstrates the enormous potential of such engineered systems: the incorporation of a bioadhesive coating, poly(butadiene-maleic anhydride-co-L-DOPA) (PBMAD), to non-bioadhesive nanospheres resulted in an enhancement of particle uptake in the small intestine from 5.8±1.9% to 66.9±12.9%. Direct correlation was obtained between bulk tensile strength, in vitro binding to everted intestinal sacs and quantitative in vivo uptake; this data suggests that bulk properties of polymers can be used to predict bioadhesive properties of nano- and microparticles. The differential distribution of the nanospheres to various tissues following uptake suggests surface chemistry plays a significant role in their localization within the body. The results of these studies provide strong support for the use of bioadhesive polymers to enhance nano- and micro-particle uptake from the small intestine for oral drug delivery.

Time-lapse, single cell based confocal imaging analysis of caspase activation and phosphatidylserine flipping during cellular apoptosis.

Apoptosis is an important phenomenon for investigating the efficacy of anti-cancer drug candidates. The conventional assays for cellular apoptosis, such as enzyme-linked immunosorbent assay, absorbance monitoring for the activity of caspase, and flow cytometric assay, have focused only on biochemical events. We investigated the staurosporine (STS)-induced apoptosis of the murine macrophage RAW-264.7 cell using a cell based bioimaging technique. Using time-lapse confocal microscopy, we monitored caspase-3 activation during apoptosis by imaging the translocation of green fluorescent protein from the cytosol to the nuclei. Five hours after 1 µM STS treatment, caspase-3 was observed to be activated and membrane blebbing was observed simultaneously. Also, the loss of phosphatidylserine (PS) asymmetry in the phospholipid bilayer of plasma membrane during early apoptosis was monitored by imaging annexin-V labeled with fluorescein isocyanate binding to the externalized PS at various concentrations of STS. Moreover, disintegration of the plasma membrane during late apoptosis was confirmed using a nuclear dye, propidium iodide. The single cell based bioimaging data agreed well with those of the biochemical assays for caspase activation and morphological observation for membrane integrity.

A ventriculoperitoneal shunt catheter wrapped around a right mammary prosthesis forming a pseudocyst.

Breast cerebrospinal fluid pseudocysts are a rare complication of ventriculoperitoneal (VP) shunting. It is very unusual for the peritoneal catheter of a shunt to become wrapped around a prosthesis a previously augmented breast. Three previously reported patients developed an enlarging breast lump and were diagnosed with shunt migration around the prosthesis. Our patient underwent bilateral breast augmentation and subsequently a VP shunt. We observed on frequent follow-up chest X-rays performed for pneumonia and mechanical ventilation that the peritoneal catheter had gradually wrapped around her prosthesis. She developed a progressively enlarging breast lump which resolved with drainage of the cerebrospinal fluid collection and revision of the VP shunt.

The effects of intravesical chemoimmunotherapy with gemcitabine and Bacillus Calmette-Guérin in superficial bladder cancer: a preliminary study.

This prospective study investigated the long-term effects of intravesical chemoimmunotherapy with gemcitabine (GEM) and bacillus Calmette-Guérin (BCG; n = 36) versus BCG alone (n = 51) for the treatment of superficial bladder cancer. For the chemoimmunotherapy (GEM + BCG) group, GEM (1000 mg) was instilled immediately after transurethral resection of bladder tumour (TURBT) and again (2000 mg) 1 week later. From 2 to 7 weeks after TURBT, BCG was instilled into the bladder of all patients once weekly. The recurrence-free period of the GEM + BCG group (24.13 months) was significantly longer than that of the BCG monotherapy group (19.81 months). The overall recurrence rate was similar between the groups, although at 6 and 9 months post-TURBT, GEM + BCG produced a significantly lower rate of recurrence compared with BCG alone. This study suggests that intravesical chemoimmunotherapy with GEM + BCG is effective in reducing early tumour recurrence and in prolonging the recurrence-free period of superficial bladder cancer.

Ferroelectricity driven by Y d0-ness with rehybridization in YMnO3.

We investigated electronic structure of hexagonal multiferroic YMnO3 using the polarization dependent x-ray absorption spectroscopy (XAS) at O K and Mn L(2,3) edges. The spectra exhibit strong polarization dependence at both edges, reflecting anisotropic Mn 3d orbital occupation. Moreover, the O K edge spectra show that Y 4d states are strongly hybridized with O 2p ones, resulting in large anomalies in Born effective charges on off-centering Y and O ions. These results manifest that the Y d(0)-ness with rehybridization is the driving force for the ferroelectricity, and suggest a new approach to understand the multiferroicity in the hexagonal manganites.

Round cell variant of myxoid liposarcoma in a Japanese Macaque (Macaca fuscata).

A 5-year-old, female, Japanese Macaque (Macaca fuscata) was diagnosed with round cell variant of myxoid liposarcoma. At necropsy, multifocal to coalescing, reddish tan to white nodules, ranging from 0.5 to 1 cm in diameter, were noted throughout the omentum and retroperitoneum. Similar neoplastic nodules were also present in diaphragm, abdominal wall, and on hepatic capsule. Microscopically, neoplastic masses consisted of round to polyhedral cells, which had round, often eccentric nuclei and abundant eosinophilic granular and microvacuolated cytoplasm; Oil red O staining demonstrated large numbers of lipid droplets in the cytoplasm. Ultrastructurally, the cytoplasm of the tumor cells was packed with occasional lipid vacuoles and numerous enlarged mitochondria. Immunohistochemistry revealed tumor cells were positive for vimentin, while negative to cytokeratin, actin, and Factor VIII-related antigen. To the authors' knowledge, this is the first report of round-cell variant of myxoid liposarcoma in nonhuman primate.

Amyloid-producing odontogenic tumour (calcifying epithelial odontogenic tumour) in the mandible of a Bengal tiger (Panthera tigris tigris).

A 13-year-old male tiger (Panthera tigris tigris) had a marked mandibular swelling noticed 12 months earlier and associated with progressive anorexia and weight loss. Radiological and post-mortem examination revealed a mass (13x15 cm) which was firm and poorly defined, with destruction of the adjacent bone tissue. Histologically, the mass was poorly demarcated, with infiltrative growth, and composed of nests, cords and islands of epithelial cells with characteristic basal cell features. Also observed were extensive squamous metaplasia, ghost cells, stellate reticulum, and fibroblastic connective tissue stroma containing inflammatory cells. A prominent feature of this tumour consisted of abundant nodular deposits of congophilic amyloid-like material with partial mineralization (Liesegang rings). Immunohistochemically, the neoplastic cells and the amyloid-like material were positive for pancytokeratin and negative for vimentin. The findings supported the diagnosis of an amyloid-producing odontogenic tumour (APOT), also known as calcifying epithelial odontogenic tumour in man and animals.

Genetic polymorphisms of OPG, RANK, and ESR1 and bone mineral density in Korean postmenopausal women.

To evaluate the effects of genetic polymorphisms of OPG, RANK, and ESR1, which regulate osteoclastogenesis, on bone mineral density (BMD), a cross-sectional study was conducted in 650 Korean postmenopausal women. BMDs of the distal radius and the calcaneus were measured by dual energy X-ray absorptiometry (DXA). Genetic polymorphisms of OPG 163 A > G, 1181 G > C; RANK 421 C > T, 575 T > C; and ESR1 1335 C > T, 2142 G > A were determined by matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) mass spectrometry. The differences between the BMDs of the genotypes of OPG, RANK, and ESR1 were analyzed by multiple linear regression model adjusted for age and body mass index. Women with the OPG 1181 CC genotype had higher BMDs at the distal radius (7%) and calcaneus (10%) than those with the GG genotype; and these differences were statistically significant (P = 0.001 and P = 0.007, respectively). A significant association was also observed between RANK 575 T > C and calcaneus BMD (P for trend = 0.017). No significant association was observed between BMDs and the polymorphisms of ESR1. The association between OPG 1181 G > C and BMD was profound in subjects with the RANK 575 TT or ESR1 2142 GG genotypes; women with OPG 1181 CC had higher BMDs at the distal radius (11%) and calcaneus (11%) than those with OPG 1181 GG only in women with RANK 575 TT genotype (P = 0.002 and P = 0.021, respectively). These results suggest that OPG genetic polymorphisms, especially with the RANK 575 TT or ESR1 2142 GG genotypes, are related to low BMD in postmenopausal Korean women.

Drought-inducible-but ABA-independent-thaumatin-like protein from carrot (Daucus carota L.).

Drought treatment induces the accumulation of dcTLP, which is similar in structure to the thaumatin-like proteins (TLPs) found in the embryogenic calli, seedlings, and mature plants of carrot (Daucus carota). We isolated a full-length dcTLP cDNA clone from carrot and characterized the 5' upstream sequences. The coding region of dcTLP consisted of 645 nucleotides; the theoretical pI value was 4.9, and its molecular weight was approximately 22 kDa. The production of dcTLP transcripts in the seedlings increased dramatically with dehydration treatment but was not affected by abscisic acid (ABA), salicylic acid, or jasmonic acid. The expression patterns of dcTLP mRNA at different developmental stages and in response to a variety of signal molecules was analyzed using reverse transcriptase-PCR and promoter analysis with fused genes of 0.5-kb 5' upstream sequences in which beta-glucuronidase (GUS) reporter genes (gus) were established. The induction of dcTLP was found to be highly specific to drought stress in the embryogenic calli, seedlings, and mature plants. Our results suggest that this new isoform of TLP that has been isolated from carrot is a drought-specific, ABA-independent, non-organ-specific, and non-developmental-stage-specific protein.

Systemic AL amyloidosis associated with multiple myeloma in a horse.

AL amyloidosis is the most common type of systemic amyloidosis in humans, and it is frequently associated with multiple myeloma. But, AL amyloidosis is very rare in domestic animals. A 16-year-old Quarter horse gelding was diagnosed with systemic AL amyloidosis associated with multiple myeloma. Clinical problems were rapid weight loss, muscle atrophy, soft unformed stool, and ventral edema. Grossly, diffuse gastrointestinal hemorrhage, markedly thickened jejunal mucosa, and splenomegaly were present. Microscopically, diffuse severe amyloid deposits were present in the lamina propria of glandular stomach, duodenum, and jejunum. Much of the spleen and sternal bone marrow was replaced by neoplastic round cells, and multiple foci of amyloid were also present in the spleen and bone marrow. Electron microscopy revealed the neoplastic round cells to be of plasma cell origin, and the amyloid showed a strongly positive immunoreactivity with polyclonal anti-human immunoglobin lambda light-chain antisera. To our knowledge, this is the second report describing systemic AL amyloidosis in domestic animals-associated plasma cell neoplasia and the first associated with multiple myeloma, as is common in humans.

Thiopurine S-methyltransferase polymorphisms and the relationship between the mutant alleles and the adverse effects in systemic lupus erythematosus patients taking azathioprine.

OBJECTIVE: The present study sought to elucidate the genetic basis of thiopurine methyltransferase (TPMT) polymorphism and subsequently to investigate the relationship between mutant TPMT and an adverse response observed in Korean patients with systemic lupus erythematosus (SLE) taking azathioprine (AZA). METHODS: The TPMT genotype of 342 patients with SLE was determined by MALDI-TOF mass spectrometry and correlated with the effects of clinical exposure to AZA. RESULTS: TPMT polymorphism was detected in 17 of the 342 study subjects (5.0%), 12 heterozygous for the TPMT*3C allele and 5 heterozygous for the TPMT*6 allele. Numerous patients taking AZA demonstrated adverse drug responses. Severe nausea occurred in 4 patients with the TPMT*3C allele, while 1 patient with the TPMT*6 allele suffered severe bone marrow toxicity. Leucopenia (n = 17), nausea (n = 4), and abnormal liver function (n = 1) were suspected in 23 of the 94 lupus patients taking AZA. AZA was relatively well tolerated by the remainder of the patients. The heterozygous genotype for the TPMT*3C and *6 alleles was frequently detected in Korean SLE patients. CONCLUSION: Contrary to previous hypotheses, this study identified no statistical correlation between TPMT genotype and AZA toxicity. We thus conclude that TMPT genotyping cannot replace regular blood monitoring in SLE patients receiving AZA treatment.

Articular chondrocyte apoptosis in equine osteoarthritis.

Osteoarthritis (OA) is the most common joint disease in horses. Chondrocyte apoptosis has been implicated as a major pathological OA change in humans and experimental animals but no studies have been performed on equine OA. Articular cartilage was collected from three normal and five OA horses. Histopathological changes were scored by a modified Mankin grading system. A terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was performed to identify chondrocyte apoptosis. Nitric oxide (NO) production from chondrocytes was indirectly evaluated by immunohistochemistry with polyclonal antibody to nitrotyrosine. The histopathological score and percentage of chondrocyte apoptosis from the OA cartilages were significantly higher than from normal cartilages. There was a significant correlation between histopathological grade and the percentage of chondrocyte apoptosis. OA cartilages exhibited stronger immunoreactivity to nitrotyrosine than normal cartilage. Topographical distributions of chondrocyte apoptosis, cartilage matrix degeneration, and NO production overlapped in equine OA cartilages, suggesting that these pathological phenomena are closely interrelated.

Malignant peripheral nerve sheath tumor with divergent mesenchymal differentiations in a dog.

A malignant peripheral nerve sheath tumor with divergent osteogenic, myxomatous, and myoblastic differentiations is described in a 10.5-year-old male Labrador Retriever dog. The tumor involved the sixth and seventh cervical spinal cord segments and nerves. The diagnosis was based on the results of histopathology, electron microscopy, and immunohistochemistry.