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.

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 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.

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.

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.

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.

Increased expression of cyclooxygenase-2 protein in human gastric carcinoma.

Gastric adenocarcinoma is one of the most common malignancies in the world, and yet little is known about its molecular process of development and progression. Recent studies have suggested that ingestion of nonsteroid anti-inflammatory drugs reduces the risk of colon cancer, presumably by inhibiting the cyclooxygenase (COX) enzyme. COX-2, one isoform of the COX enzyme, is the rate-limiting enzyme in prostaglandin synthesis, and the function of this enzyme is thought to relate to inflammatory processes and carcinogenesis. To understand the role of COX enzyme in gastric cancer, we measured COX-2 expression in 104 human gastric carcinoma tissues by immunohistochemical analysis. We obtained tissue specimens from 104 surgically resected gastric adenocarcinoma patients. We performed immunohistochemical stain for human COX-2 with polyclonal antibody in gastric carcinoma. After curative resection and extensive lymph node dissection, all patients received adjuvant chemotherapy containing 5-fluorouracil. Expression of COX-2 showed cytoplasmic staining, not only in cancer cells but also in precancerous lesions such as metaplastic and adenomatous cells. We confirmed up-regulation of COX-2 in gastric cancer tissues compared with normal paired mucosa using Western blot analysis. There was no correlation between clinicopathological characteristics of gastric cancer patients and intensity of COX-2 protein expression. This study indicates that COX-2 protein over-expression may contribute to an early event of gastric cancer development, and it further suggests that selective inhibition of COX-2 may provide a chemopreventive effect against gastric carcinogenesis.

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.

Comparison of the APACHE III, APACHE II and Glasgow Coma Scale in acute head injury for prediction of mortality and functional outcome.

OBJECTIVES: This study examines the efficacy of the predicting power for hospital mortality and functional outcome of three different scoring systems for head injury in a neurosurgical intensive care unit (NICU). DESIGN: On the day of admission, data were collected from each patient to compute the Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II and III, and Glasgow Coma Scale (GCS) scores. Hospital mortality was defined as the deaths of patients before discharge from hospital. Early mortality was defined as death before the 14th day after admission. Late mortality was defined as death after the 15th day from admission. Functional outcome was evaluated by Index of Independence in Activities of Daily Living (Index of ADL). SETTING: An 8-bed NICU in a 1270-bed medical center in Taichung Veterans General Hospital. PATIENTS AND PARTICIPANTS: Two hundred non-selected patients with acute head injury were included in our study in a consecutive period of 2 years. Patients less than 14 years old were not included. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Sensitivity, specificity and correct prediction outcome were measured by the chi-square method in three scoring systems. The Youden index was also obtained. The best cut-off point in each scoring system was determined by the Youden index. The difference in Youden index was calculated by Z score. A difference was also considered if the probability value was less than 0.05. The area under Receiver Operating Characteristic (ROC) curve was computed. Then the area under ROC of each scoring system was compared by Z score. There was statistical significance if p was less than 0.05. For prediction of hospital mortality, the best cut-off points are 55 for APACHE III, 17 for APACHE II and 5 for GCS. The correct prediction outcome is 82.4% in APACHE III, 78.4% in APACHE II and 81.9% in the GCS. The Youden index has best cut-off points at 0.68 for APACHE III 0.59 for APACHE II, and 0.56 for GCS. The area under Receiver Operating Characteristic (ROC) curve is 0.90 in the APACHE III, 0.84 in the APACHE II and 0.86 in the GVS. There are no statistical differences among APACHE III and II, and GCS in terms of correct prediction outcome, Youden Index and the area under the ROC curve. Other physiological variables excluding GCS in APACHE III and II (AP III-GCS, AP II-GCS) have less statistical value in the determination of mortality for acute head injury. For the prediction of late mortality, APACHE III and II yield significantly better results in the area under the ROC curve, correct prediction and Youden index than those of GCS. Other physiological variables (AP III-GCS and AP II-GCS) play an important role in the prediction of late mortality in APACHE scores. For prediction of the functional outcome of surviving patients with acute head injury, the APACHE III yields the best results of correct prediction outcome, Youden index and the area under the ROC curve. CONCLUSION: The APACHE III and II may not replace the role of GCS in cases of acute head injury for hospital or early mortality assessment. But for prediction of the late mortality, the APACHE III and II have better accuracy than GCS. Other physiological variables excluding GCS in the APACHE system play a crucial contribution for late mortality. GCS is simple, less time-consuming and economical for patients with acute head injury for the prediction of hospital and early mortality. The APACHE III provides better prediction for severe morbidity than GCS and APACHE II. Therefore, the APACHE III provides a good assessment not only for hospital and late mortality, but also for functional outcome.

Repeat operations in failed microvascular decompression for trigeminal neuralgia.

For the study of pathogenesis and treatment of recurrent trigeminal neuralgia, we performed 31 repeat operations from among 400 patients with trigeminal neuralgia in the past 10 years. Initially, of these 400 patients, 376 underwent microvascular decompression only, and 24 underwent partial sensory rhizotomy with or without microvascular decompression. Fifty-three patients (14%) had recurrences after microvascular decompression, of which 31 patients underwent repeat operations. Among the repeat operations, there was negative exploration in 16 patients (52%), arterial loop compression in 7 (22%), venous compression in 4 (13%), and Teflon compression or adhesion in 4 (13%). Twenty-one patients had early recurrences within 1 year, and 10 patients had late recurrences. Negative exploration and arterial compression were more likely in early recurrence (P = 0.01). Continuing demyelination might occur in patients with negative exploration, even when adequate decompression had been initially performed. Seventy percent of the patients had no recurring pain by way of partial sensory rhizotomy for negative explorations, redecompression of arterial loops, division of offending veins, or lysis and reposition of Teflon. About half of the patients had positive findings that were amenable without rhizotomy in the repeat operations. A repeat operation for failed microvascular decompression is a good choice if the condition of the patient is tolerant.

A brain MRI study in subjects with borderline personality disorder.

BACKGROUND: There have been only a few brain computed tomography imaging studies, with mostly negative findings, in subjects with borderline personality disorder (BPD). This is the first MRI study which evaluated the structural abnormalities of the brain in subjects with the sole diagnosis of BPD. METHODS: Twenty-five subjects with BPD were compared with age-, gender-matched healthy comparison subjects (n=25) on volumes of the frontal lobes, the temporal lobes, the lateral ventricles, and the cerebral hemispheres in brain magnetic resonance imaging. RESULTS: Subjects with BPD had a significantly smaller frontal lobe compared to comparison subjects (multivariate regression analysis, t=2.225, df=46, P=0.031). There were no significant differences in volumes of the temporal lobes, the lateral ventricles, and the cerebral hemispheres between subjects with and without BPD. LIMITATIONS: Strict inclusion and exclusion criteria employed in the present study may make it difficult to generalize our findings. The gray matter and white matter of the brain were not measured separately. Differences in head tilt during image acquisition were not corrected. CONCLUSIONS: The current study reports a smaller frontal lobe volume on brain MRI in subjects with BPD compared with healthy comparison subjects. This finding may serve as a potentially useful biological variable that may allow for subtyping BPD.

Enhanced production and germination of somatic embryos by temporary starvation in tissue cultures of Daucus carota.

Embryogenic callus was induced from cotyledonary explants of Daucus carota L. cultured on solidified MS medium supplemented with 1 mg l-1 2,4-D. Following callus initiation somatic embryos were developed from the callus on MS medium without 2,4-dichlorophenoxyacetic acid. To stimulate the production and germination of somatic embryos we cultured the callus under physically and chemically modified conditions during subculture. When the embryogenic callus was cultured on half-strength MS medium or MS medium without sucrose or cultured under conditions of reduced humidity (69.3%), the production of embryos increased 3.4- to 4.5-fold compared to culture on MS medium containing 3% sucrose (control). Embryogenic callus cultured on MS medium after 5 days of starvation (by being placed in empty 12-well tissue culture plates) showed a 20-fold increase in somatic embryo production and enhanced maturation and germination of embryos. An important point is that the germination of somatic embryos with cup-shaped cotyledons, after a period in culture without medium, was remarkably improved (92%) compared to that of the controls (23%).Thus, we were able to show that stress by starvation without medium led to the enhanced production and increased germination of somatic embryos.

Hereditary neuraxial edema in Polled Hereford calves.

Two newborn Polled Hereford calves with hereditary neuraxial edema were available for clinical and pathological examination. The affected animals showed extensor spasms and were unable to rise. Pathologic lesions were microscopic and consisted of widespread vacuolation of the neuraxis, chiefly in white matter and less markedly in grey matter. The lesions were most severe in the brain stem and cerebellar white matter. Examination of the breeding record indicated sire-daughters matings and thus a probably autosomal recessive mode of inheritance.

Intradural metastasis to the cauda equina from carcinoma of the anus.

STUDY DESIGN: This is a report of a man with carcinoma of the anus and intradural metastasis to the cauda equina. OBJECTIVE: To perform a laminectomy with tumor removal for relief of pain. SUMMARY OF BACKGROUND DATA: Only 25 cases of intradural spinal metastasis have been reported in the English literature. This is the first report of a metastatic case, moving from the carcinoma of the anus to the cauda equina. METHODS: Magnetic resonance imaging showed an ill-defined mass, with central necrosis, to the cauda equina. The possibility of intradural metastasis to the cauda equina was indicated by unique pain symptoms. RESULTS: The patient's back pain subsided after total laminectomy of L3-L5 with subtotal removal of the tumor. The residual tumor became smaller with postoperative radiation. CONCLUSION: Magnetic resonance imaging is a good diagnostic choice in this situation. The cause of the metastasis was unclear, but it was presumed to have occurred through the perineural lymphatic ducts. Laminectomy with tumor removal is feasible for relieving pain and demonstrating pathology.

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.

Intracranial lipoma in the medulla oblongata.

Intracranial lipoma in the medulla oblongata has been rarely reported. Only two cases have been documented in the literature. This report concerns a patient who complained of nuchal soreness and an unstable gait for 6 months. An olivelike lipoma, arising from the posterior aspect of the medulla oblongata and embedded in the lower cranial nerves, was found at suboccipital craniectomy and posterior laminectomy of C1-2. Partial removal of the lipoma was performed for decompression; radical removal would have been hazardous. The clinical symptoms subsided postoperatively. The computed tomography scan and magnetic resonance image proved useful for properative diagnosis.

Eastern equine encephalitis in a flock of emus (Dromaius novaehollandiae).

Eastern equine encephalitis (EEE) was diagnosed in a flock of emus in southeastern Louisiana. The outbreak involved juvenile and adult breeders ranging in age from 20 to 36 months, with an attack rate of 76% and a case fatality rate of 87%. The diagnosis was confirmed by isolation and characterization of the viral agent, and by detection of EEE antibody in two recovered emus. High mortality was preceded by marked depression, hemorrhagic diarrhea, and emesis of blood-stained ingesta. On postmortem examination, hemorrhagic enteritis and multiple petechia of viscera were observed. Microscopic changes included severe necrosis of hepatocytes, intestinal mucosa, and necrotizing vasculitis of the spleen and lamina propria of the intestine. No nervous system lesions were observed. This outbreak occurred concurrently with EEE in horses and was attributed to unseasonably heavy rainfall with an abundance of arthropod vectors and proximity to free-living reservoir host species.