CLCU-Net: Cross-level connected U-shaped network with selective feature aggregation attention module for brain tumor segmentation.

BACKGROUND AND OBJECTIVE: Brain tumors are among the most deadly cancers worldwide. Due to the development of deep convolutional neural networks, many brain tumor segmentation methods help clinicians diagnose and operate. However, most of these methods insufficiently use multi-scale features, reducing their ability to extract brain tumors' features and details. To assist clinicians in the accurate automatic segmentation of brain tumors, we built a new deep learning network to make full use of multi-scale features for improving the performance of brain tumor segmentation. METHODS: We propose a novel cross-level connected U-shaped network (CLCU-Net) to connect different scales' features for fully utilizing multi-scale features. Besides, we propose a generic attention module (Segmented Attention Module, SAM) on the connections of different scale features for selectively aggregating features, which provides a more efficient connection of different scale features. Moreover, we employ deep supervision and spatial pyramid pooling (SSP) to improve the method's performance further. RESULTS: We evaluated our method on the BRATS 2018 dataset by five indexes and achieved excellent performance with a Dice Score of 88.5%, a Precision of 91.98%, a Recall of 85.62%, a Params of 36.34M and Inference Time of 8.89ms for the whole tumor, which outperformed six state-of-the-art methods. Moreover, the performed analysis of different attention modules' heatmaps proved that the attention module proposed in this study was more suitable for segmentation tasks than the other existing popular attention modules. CONCLUSION: Both the qualitative and quantitative experimental results indicate that our cross-level connected U-shaped network with selective feature aggregation attention module can achieve accurate brain tumor segmentation and is considered quite instrumental in clinical practice implementation.

Modelling end-pumped passively Q-switched Nd-doped crystal lasers: manifestation by a Nd:YVO4/Cr4+:YAG system with a concave-convex resonator.

A theoretical model for the passively Q-switched (PQS) operation which includes the spatial overlapping between the pump and lasing modes under the thermal lensing effect is developed to give a transcendental equation that can directly determine the critical parameters such as pulse energy, pulse repetition rate, and pulse width for the PQS performance. More importantly, an analytical function which gives the approximate solution for the transcendental equation as well as a specific critical criterion for good PQS operation are derived for practical analyses and design. A Nd:YVO4/Cr4+:YAG system with a concave-convex resonator which can achieve fairly stable PQS pulse trains even at a high pump level is further exploited to manifest the proposed spatially dependent model. The good agreement between the experimental results and the theoretical predictions is verified to show the feasibility of the proposed model for designing high-power PQS lasers with high accuracy.

Distinct long-term neurocognitive outcomes after equipotent sevoflurane or isoflurane anaesthesia in immature rats.

BACKGROUND: Many anaesthetics when given to young animals cause cell death and learning deficits that persist until much later in life. Recent attempts to compare the relative safety or toxicity between different agents have not adequately controlled for the relative dose of anaesthetic given, thereby making direct comparisons difficult. METHODS: Isoflurane or sevoflurane were given at 1 minimum alveolar concentration (MAC) for 4 h to postnatal day 7 (P7) rat pups. Beginning at P75 these animals underwent fear conditioning and at P83 Morris water maze testing to assess working memory, short-term memory and early long-term memory using delays of 1 min, 1 h, and 4 h. RESULTS: No difference between groups was seen in fear conditioning experiments. Morris water maze learning was equivalent between groups, and no difference was seen in working memory. Sevoflurane-treated animals had a deficit in early long-term memory, and isoflurane-treated animals had a deficit in both short-term and early long-term memory. CONCLUSIONS: Both isoflurane and sevoflurane delivered at 1 MAC for 4 h to immature rats caused a deficit in long-term memory. Isoflurane also caused a deficit in short-term memory. Isoflurane might be more detrimental than sevoflurane in very young animals.

Radiotherapy with volumetric modulated arc therapy for hepatocellular carcinoma patients ineligible for surgery or ablative treatments.

PURPOSE: The aim of this article is to report the dosimetric and clinical findings in the treatment of primary hepatocellular carcinoma (HCC) with volumetric modulated arc therapy (VMAT, RapidArc). METHODS AND MATERIALS: A total of 138 patients were investigated. Dose prescription ranged from 45-66 Gy. Most patients (88.4 %) presented AJCC stage III or IV and 83 % were N0-M0. All were classified as Barcelona Clinic Liver Cancer (BCLC) stage A-C. All patients were treated using 10 MV photons with single or multiple, coplanar or non-coplanar arcs, and cone-down technique in case of early response of tumors. RESULTS: The patients' median age was 66 years (range 27-87 years), 83 % were treated with 60 Gy (12 % at 45 Gy, 6 % at 66 Gy), 62 % with cone-down, 98 % with multiple arcs. The mean initial planning target volume (PTV) was 777 ± 632 cm(3); the mean final PTV (after the cone-down) was 583 ± 548 cm(3). High target coverage was achieved. The final PTV was V98% > 98 %. Kidneys received on average 5 and 8 Gy (left and right), while the maximum dose to the spinal cord was 22 Gy; mean doses to esophagus and stomach were 23 Gy and 15 Gy, respectively. The average volume of healthy liver receiving more than 30 Gy was 294 ± 145 cm(3). Overall survival at 12 months was 45 %; median survival was 10.3 months (95 % confidence interval 7.2-13.3 months). Actuarial local control at 6 months was 95 % and 93.7 % at 12 months. The median follow-up was 9 months and a maximum of 28 months. CONCLUSION: This study showed from the dosimetric point of view the feasibility and technical appropriateness of RapidArc for the treatment of HCC. Clinical results were positive and might suggest, with appropriate care, to consider RapidArc as an additional therapeutic opportunity for these patients.

Efficacy of mirtazapine in preventing intrathecal morphine-induced nausea and vomiting after orthopaedic surgery*.

Nausea and vomiting are frequent complications of intrathecal morphine. In this randomised, double-blind trial, we tested the efficacy of mirtazapine, an antidepressant that blocks receptors associated with vomiting, on the incidence of nausea and vomiting after intrathecal morphine. One hundred patients receiving spinal anaesthesia for lower limb surgery were assigned equally to take either an orally disintegrating form of 30 mg mirtazapine or matching placebo 1 h before surgery. Spinal anaesthesia was performed by injection of 15 mg isobaric bupivacaine 0.5% along with 0.2 mg preservative-free morphine. Nausea and vomiting were evaluated 3, 6, 12, 18 and 24 h after intrathecal morphine administration. The incidence of nausea and vomiting was significantly lower in patients receiving mirtazapine compared with placebo (26.5% vs 56.3%, respectively; p = 0.005). The mean (SD) onset time of postoperative nausea and vomiting was significantly delayed in mirtazapine patients: 9.4 (2.5) vs 5.2 (1.8) h, respectively; p < 0.0001. The severity of nausea and vomiting was also decreased after mirtazapine at the 3-6 h and 6-12 h periods. Our data indicate that pre-operative mirtazapine decreases the incidence, delays the onset and reduces the severity of nausea and vomiting induced by intrathecal morphine in patients undergoing spinal anaesthesia.

Prophylactic mirtazapine reduces intrathecal morphine-induced pruritus.

BACKGROUND: Activation of the serotonergic system is an important factor in the pathogenesis of intrathecal morphine-induced pruritus. Mirtazapine is a new antidepressant that selectively blocks 5-HT(2) and 5-HT(3) receptors. We therefore tested the hypothesis that preoperative mirtazapine would reduce the incidence of intrathecal morphine-induced pruritus. METHODS: One hundred and ten ASA I patients undergoing lower limb surgery under spinal anaesthesia were randomly allocated into two equal groups and received either mirtazapine 30 mg or an orally disintegrating placebo tablet 1 h before operation in a prospective, double-blinded trial. All patients received an intrathecal injection of 15 mg of 0.5% isobaric bupivacaine and 0.2 mg preservative-free morphine. The occurrence and the severity of pruritus were assessed at 3, 6, 9, 12, and 24 h after intrathecal morphine. RESULTS: Pruritus was significantly more frequent in the placebo group compared with the mirtazapine group (75% vs 52%, respectively; P=0.0245). The time to onset of pruritus in the two groups was also significantly different. The patients who experienced pruritus in the placebo group had a faster onset time than that in the mirtazapine group [mean (sd): 3.2 (0.8) vs 7.2 (4.1) h, P<0.0001]. CONCLUSIONS: Mirtazapine premedication prevents pruritus induced by intrathecal morphine in patients undergoing lower limb surgery with spinal anaesthesia.

The feasibility study of the octane-enhancing process: isobutylene dimerization using C4 mixture.

The dimerization of isobutylene to diisobutylene in C4 mixture was evaluated using various catalysts such as nickel salts system, zeolite system and acidic ion exchange resin. There were shown that the strong acidic type ion exchange resin (Amberlyst 15) under 6 kg/cm2 and 60 degrees C gave rise to 90% conversion and more than 60% selectivity to diisobutylene with acceptable amounts of oligomer as a best catalyst. Therefore, Amberlyst 15 was employed to investigate the optimum reaction condition. In the batch reaction, since the catalyst activity was increased with the increasing reaction temperature, the reaction time should be shortened appropriately to prevent a high yield of oligomer. The reaction rate was increased by the increased amount of catalyst without much change in the product composition. The formation of oligomer was inhibited when a small amount of organic solvents (methyl tert-butyl ether) are attended. In the fixed-bed study, the results indicate that the increase in reaction temperature was accompanied by the increase in reaction rate, however, the selectivity to the dimer was affected. Higher WHSV will enhance the selectivity but reduce the conversion. Conclusively, the appropriate reaction condition was 45 degrees C with WHSV of 10.

Effects of different exercise modes on mineralization, structure, and biomechanical properties of growing bone.

Weight bearing during exercise plays an important role in improving the mechanical properties of bone. The effect on bone of non-weight-bearing exercise such as swimming remains controversial. To investigate the effects of exercise mode on growing bone, 29 male Wistar rats (7 wk old) were randomly assigned to a running exercise group (Run, n = 9), a swimming exercise group (Swim, n = 10), or a nonexercise control group (Con, n = 10). During an 8-wk training session (20-60 min/day, 5 days/wk), the Run rats were trained at progressively increasing running speeds (12-22 m/min), and weights attached to the tail of the Swim rats were progressively increased from 0 to 2% of their body weight. The bone mineral density of the proximal tibiae of the Run rats was significantly higher than in the Swim (P < 0.05). Femoral wet weights of the two exercise groups were significantly higher than in the control group (P < 0.05). Interestingly, the percent difference between the tissue wet weight and dry weight (water content ratio), which is related to bone mechanical properties, was significantly higher in the tibiae of the Swim rats and the femora of both exercise groups compared with controls (P < 0.05). Extrinsic as well as intrinsic biomechanical material properties were measured in a three-point bending test. Bone mechanical properties of the tibiae and femora of rats in the Swim and Run groups were significantly greater than those in the control group (P < 0.05). In summary, different modes of exercise may benefit bone mechanical properties in different ways. The specific effects of swimming exercise (non-weight-bearing exercise) on bone require further study.

Various forms of mutant p53 confer sensitivity to cisplatin and doxorubicin in bladder cancer cells.

PURPOSES: The nature of p53 mutation has been reported to affect cellular responses to chemotherapy. We characterized the impact of p53 mutations on drug resistance in bladder cancer cells. METHODS AND METHODS: Various human p53 mutants (V143A, V173L, H179Q, N247I and R273H) were introduced to the TCC-SUP bladder carcinoma cell line to establish stable transfectants. The expression of mutant p53 was demonstrated by reverse transcriptase-polymerase chain reaction and immunocytochemical analysis. The sensitivity to cisplatin and doxorubicin in these transfectants was determined by trypan blue exclusion. Cell death mediated by cisplatin and doxorubicin was characterized by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling analysis, Hoechst 33258 staining and annexin-V binding assay. RESULTS: The expression of all forms of mutant p53 protein except p53His273 enhanced sensitivity to cisplatin and doxorubicin. The chemosensitivity of p53His273 transfectants is similar to that of parental TCC-SUP and control transfectants. Cisplatin induced cell death undergoes apoptosis, as demonstrated by Hoechst staining, annexin-V assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling, respectively. In contrast, doxorubicin induced cell death probably occurs through a nonapoptotic pathway. CONCLUSIONS: These results indicated that the nature of p53 mutations may affect the cellular response to anticancer drugs and many forms of mutant p53 protein may enhance chemosensitivity through apoptotic or nonapoptotic pathways in bladder cancer cells.

Exogenous mutant p53 DNA enhanced cisplatin-induced apoptosis in TSGH-8301 human bladder cancer cells.

BACKGROUND: The influence of tumor suppressor gene p53 on the apoptosis of bladder cancer cells is not completely understood. In this study, the requirement for p53 in the cisplatin-induced apoptosis of human bladder cancer cells TSGH-8301 was investigated. MATERIALS AND METHODS: TSGH-8301 cells, which contain endogenous wild type p53 genes, were transfected with expression vectors containing p53 cDNA mutated at codon 173. Stable mutant p53 transfectant clones were confirmed by Southern blotting and Western blotting. The cellular response to cisplatin was determined on the basis of (a) cells viability, (b) apoptotic DNA fragmentation, and (c) nuclear condensation. RESULTS: Cells containing an exogenous mutant p53 sequence had increased sensitivity to cisplatin by undergoing apoptosis compared with parental TSGH8301 cells. In contrast, no difference was observed in those clones with rearranged or undetectable exogenous mutant p53 cDNA. However, analysis of p53 mRNA with RT-PCR sequencing indicated that none of the transfectant clones expressed exogenous mutant p53 mRNA. CONCLUSION: The transfectants had lost the expression of mutant p53 during selection; however, they could still enhance the expression of wild-type p53, which conferred sensitivity to cisplatin. IMPLICATION: Transient expression of mutant p53 protein in TSGH8301 cells may induce an irreversibly stabilization of p53 and increase the steady state of p53 expression.

The relationship between p53 status and anticancer drugs-induced apoptosis in nine human bladder cancer cell lines.

To study the relationship between the p53 status and chemotherapeutic drug-induced apoptosis, we have assessed the extent of apoptosis in nine bladder cancer cell lines during the treatment of adriamycin, cisplatin and methotrexate. Apoptosis was measured by the DNA fragmentation and merocyanine 540 (MC540) staining methods. Among the nine human bladder cancer cell lines, both wt-p53- and mut-p53-expressing cell lines (p53+/-) underwent apoptosis in response to anticancer drugs treatment. While the J82 (p53-/-) and TCCSUP (p53+/+) cell lines showed little or no apoptosis to these agents. Similar results were obtained when subjected to low doses of anticancer drug treatment. Interestingly, our results suggested that bladder cancer cells heterozygous for mutant p53 (+/-) seem to be most susceptible to chemotherapeutic drug. We therefore postulate that p53 mutations do not always provide a selective advantage in the development of chemoresistance, at least in bladderer tumor cell lines.

Clinical criteria for the diagnosis of vascular dementia: a multicenter study of comparability and interrater reliability.

BACKGROUND: Several clinical criteria have been developed to standardize the diagnosis of vascular dementia (VaD). Significant differences in patient classification have been reported, depending on the criteria used. Few studies have examined interrater reliability. OBJECTIVE: To assess the concordance in classification and interrater reliability for the following 4 clinical definitions of VaD: the Hachinski Ischemic Score (HIS), the Alzheimer Disease Diagnostic and Treatment Centers (ADDTC), National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN), and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). METHODS: Structured diagnostic checklists were developed for 4 criteria for VaD, 2 criteria for Alzheimer disease (AD), and 4 criteria for dementia. Twenty-five case vignettes, representing a spectrum of cognitive impairment and subtypes of dementia, were prepared in a standardized clinical format. Concordance in case classification using different criteria and interrater reliability among 7 ADDTCs given a specific set of criteria was assessed using the kappa statistic. RESULTS: The frequency of a diagnosis of VaD was highest using the modified HIS or DSM-IV criteria, intermediate using the original HIS and ADDTC criteria, and lowest using the NINDS-AIREN criteria. Scores for interrater reliability ranged from kappa = 0.30 (ADDTC) to kappa = 0.61 (original HIS). CONCLUSIONS: Clinical criteria for VaD are not interchangeable. Depending on the criteria selected, the reported prevalence of VaD will vary significantly. The traditional HIS has higher interrater reliability than the newer criteria for VaD. Prospective longitudinal studies with clinical-pathological correlation are needed to compare validity.

Postoperative intramuscular dextromethorphan injection provides postoperative pain relief and decreases opioid requirement after hemorrhoidectomy.

BACKGROUND: Previous studies have shown that dextromethorphan (DM) produces an analgesic/antihyperalgesic effect. This study was designed to examine whether postoperative DM intramuscular (i.m.) injection could reduce post-hemorrhoidectomy pain. METHODS: At the end of the surgery, patients in the study group (n = 30) were given an intramuscular injection of 40 mg DM and 20 mg chlorpheniramine (CPM) while in the study group (n = 30), the patients were given intramuscular 20 mg CPM only. Pethidine (1 mg/kg, i.m.) was prescribed for postoperative pain relief if required. The time to first pethidine injection, total pethidine consumption, worst pain score, and pethidine-related side effects were recorded for 48 h postoperatively. RESULTS: The time from the end of operation to the first pethidine injection was 5.4 +/- 1.6 h and 17.8 +/- 3.7 h (P = 0.006) in the control group and the study group, respectively. Total pethidine consumption was 139.5 +/- 11.5 mg and 77.5 +/- 12.2 mg (P < 0.001) in the control group and the study group, respectively. The worst VAS score was 7.5 +/- 0.2 and 7.1 +/- 0.2 (P = 0.09) in the control and the study groups, respectively. The number of patients who required pethidine injection was 29 and 21 (P < 0.005) in the control and the study groups, respectively. The number of patients who suffered pethidine-related side effects was 7 and 1 (P < 0.025) in the control and the study groups, respectively. CONCLUSIONS: We found that intramuscular DM given at the end of operation could provide good postoperative pain relief and decrease the pethidine requirement after hemorrhoidectomy.

Low flow dural arteriovenous shunt: another cause of "sinister" Tolosa-Hunt syndrome.

A 73-year-old man developed acute, painful, ophthalmoplegia. The pain improved with oral steroids and a diagnosis of Tolosa-Hunt syndrome was made. Review of his angiogram revealed a low flow dural arteriovenous shunt that drained posteriorly. Dural arteriovenous shunts may thus be another cause of "sinister" Tolosa-Hunt syndrome.

A method for quantification of astrocytic processes reveals laminar differences in the dentate gyrus but not in CA1 of the hippocampal formation.

The distribution of astrocytic processes in the dentate gyrus molecular layer and CA1 subregion of the hippocampal formation was examined in 8-microns frozen sections from adult male rats. The stereological cycloid intersection method (Baddeley et al., 1986) was used to estimate surface density of glial fibrillary acidic protein-immunoreactive astrocytic processes. A distinct lamination pattern was delineated in the dentate gyrus which corresponds to the afferent input to this region. No such pattern was detectable in s. radiatum of CA1. By using this relatively new stereological method which utilizes a sensitive sampling scheme, it was possible to increase the reliability in reporting the distribution of fine processes while at the same time greatly reducing the amount of time necessary to estimate the amount of astrocytic processes in a given region.

Astrocytic and synaptic response to kindling in hippocampal subfield CA1. II. Synaptogenesis and astrocytic process increases to in vivo kindling.

Astrocytic glia are important for maintaining synaptic function during physiological activity. Recent hypotheses concerning epilepsy suggest a role for astrocytes in the control of neuronal excitability and in pathogenesis. This report provides morphological evidence that the periodic electrical stimulation used in the kindling model of epilepsy induces astrocytic hypertrophy and an increase in shaft synapse density in the CA1 region of the hippocampus. The Schaffer collateral pathway in the stratum radiatum of CA1 of five pairs of rats was kindled in vivo. Control animals received the same number of stimulations at a lower intensity and frequency. The animals were killed 24-48 h after reaching the criterion of five generalized seizures, and the brains were examined by electron microscopy. Kindling produced a 37% and 33% increase in the volume fraction of astrocytic processes in the middle and distal portions, respectively, of the s. radiatum in CA1. In the same tissue, the number (areal density) of shaft synapses was increased 25% in the s. radiatum of animals exhibiting generalized seizures. On the other hand, the areal density of degenerating synapses in both kindled and control animals was low and not significantly different. These results suggest that both synaptogenesis and hypertrophy of astrocytes contribute to an early stage of epileptogenesis when degenerative changes of the sort that might induce gliosis were not prominent in the tissue under study.

Astrocytic and synaptic response to kindling in hippocampal subfield CA1. I. Synaptogenesis in response to kindling in vitro.

Early morphological events associated with the genesis of epileptiform activity are essentially unknown, despite significant progress on morphological correlates of potentially related plastic neural phenomena. Hippocampal area CA1 shows the capacity to generate epileptiform bursting activity after certain patterns of electrical stimulation. Using an in vitro slice kindling preparation, we found increases in the numbers (areal densities) of shaft and sessile spine synapses in hippocampal subfield CA1 within minutes following the establishment of stable afterdischarges. These data strongly suggest that synaptogenesis is associated with the early stages of epilepsy formation.

Central autonomic disorders.

Central autonomic dysfunctions can be due to primary (degenerative) or secondary disorders. Autonomic failure (AF) may be a major manifestation of multiple system atrophy (MSA) and idiopathic Parkinson's disease (IPD). In both MSA and IPD, AF is almost invariably associated with neuronal loss in the intermediolateral cell columns. Dysautonomia in MSA is early, severe, and progressive, including marked orthostatic hypotension and urinary incontinence and is complicated by respiratory disturbances, such as laryngeal stridor and sleep apnea. MSA/AF can be differentiated from primary (or pure) autonomic failure (PAF) without central nervous system involvement. PAF is mainly a disorder of the postganglionic neurons. In contrast to PAF, MSA/AF has preserved basal sympathetic activity, decreased cerebrospinal fluid (CSF) neurotransmitter markers, impaired vasopressin response to hypotension, and impaired adrenocorticotrophic hormone/beta endorphin response to hypoglycemia. AF in IPD is generally less severe than in MSA. Poor response to L-Dopa, abnormal urethral sphincter electromyography, and CSF markers may distinguish MSA from IPD. Secondary autonomic disorders may result from traumatic, vascular, inflammatory, demyelinating, or neoplastic lesions involving corticolimbic, hypothalamic, brainstem, or spinal autonomic network. These disorders can cause AF or autonomic hyperactivity, such as arrhythmia, hypertension, and hyperthermia. However, many disorders may only produce subclinical abnormalities.

Functional study of hepatitis delta virus large antigen in packaging and replication inhibition: role of the amino-terminal leucine zipper.

The large hepatitis delta antigen (HDAg) has been found to be essential for the assembly of the hepatitis delta virion. Furthermore, in a cotransfection experiment, the large HDAg itself, without the hepatitis delta virus (HDV) genome and small HDAg, could be packaged into hepatitis B surface antigen (HBsAg) particles. By deletion analysis, it was shown that the amino-terminal leucine zipper domain was dispensable for packaging. The large HDAg could also help in copackaging of the small HDAg into HBsAg particles without the need for HDV RNA. This process was probably mediated through direct interaction of the two HDAgs as a mutated large HDAg whose leucine zipper domain was deleted such that it could not help in copackaging of the small HDAg. This mutated large HDAg did not suppress HDV replication, suggesting that this effect is probably also via protein interaction. These results indicated that functional domains of the large HDAg responsible for packaging with HBsAg particles and for the trans-negative effect on HDV replication can be separated.