The neurobiological reward system in Prolonged Grief Disorder (PGD): A systematic review.

Prolonged Grief Disorder (PGD) is a debilitating condition affecting between 7% and 10% of bereaved individuals. Past imaging and psychological studies have proposed links between PGD's characteristic symptoms - in particular, profound yearning - and the neural reward system. We conducted a systematic review to investigate this connection. On December 19, 2019, we searched six bibliographic databases for data on the neurobiology of grief and disordered grief. We excluded studies of the hypothalamic-pituitary-adrenal (HPA) axis, animal studies, and reviews. After abstract and full-text screening, twenty-four studies were included in the final review. We found diverse evidence for the activation of several reward-related regions of the brain in PGD. The data reviewed suggest that compared to normative grief, PGD involves a differential pattern of activity in the amygdala and orbitofrontal cortex (OFC); likely differential activity in the posterior cingulate cortex (PCC), rostral or subgenual anterior cingulate cortex (ACC), and basal ganglia overall, including the nucleus accumbens (NAc); and possible differential activity in the insula. It also appears that oxytocin signaling is altered in PGD, though the exact mechanism is unclear. Our findings appear to be consistent with, though not confirmative of, conceptualizing PGD as a disorder of reward, and identify directions for future research.

Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women.

OBJECTIVE: Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC risk in Asian women. METHODS: Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631 SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations. RESULTS: At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio [OR] = 1.34, P = 8.7 × 10-9) and high-grade serous EOC (HGSOC) (OR = 1.34, P = 4.3 × 10-9). SNP rs6902488 at 6p25.2 (r2 = 0.97 with rs7748275) lies in an active enhancer and is predicted to impact binding of STAT3, P300 and ELF1. We identified additional risk loci with low Bayesian false discovery probability (BFDP) scores, indicating they are likely to be true risk associations (BFDP <10%). At chromosome 20q11.22, rs74272064 was associated with HGSOC risk (OR = 1.27, P = 9.0 × 10-8). Overall EOC risk was associated with rs10260419 at chromosome 7p21.3 (OR = 1.33, P = 1.2 × 10-7) and rs74917072 at chromosome 2q37.3 (OR = 1.25, P = 4.7 × 10-7). At 2q37.3, expression quantitative trait locus analysis in 404 HGSOC tissues identified ESPNL as a putative candidate susceptibility gene (P = 1.2 × 10-7). CONCLUSION: While some risk loci were shared between East Asian and European populations, others were population-specific, indicating that the landscape of EOC risk in Asian women has both shared and unique features compared to women of European ancestry.

Surgical Management of Sacrococcygeal Region Giant Tumors by Use of Balloon Occlusion Abdominal Aorta.

AIM: Sacrococcygeal region giant tumors are a challenge for neurosurgeons. The purpose of this paper was to retrospectively analyze the clinical records of sacrococcygeal region giant tumors treated surgically by balloon occlusion of the abdominal aorta. MATERIAL AND METHODS: A total of 130 patients of sacral region tumors underwent surgery in our department from February 2009 to February 2013. Among these patients, 35 giant tumors were treated by balloon catheter occlusion of the abdominal aorta and electrophysiological monitoring. Thirty patients returned for follow-up evaluations and their clinical and imaging records were analyzed. RESULTS: Thirty patients underwent surgery via a posterior approach; these cases included 21 chordomas, 5 schwannomas, and 4 giant cell tumors of bone. Wide resections were performed in 26 patients (86.7%) and margin resections were performed in 4 (13.3%) patients. Most patients' symptoms were relieved through surgery and only nine patients (30%) experienced recurrence of the tumors during follow-up. CONCLUSION: Sacrococcygeal region giant tumors are still difficult to treat, especially for malignant tumors. Balloon catheter occlusions of the lower abdominal aorta can notably decreased intraoperative hemorrhage, shorten operation time, and decrease postoperative complications. This method is a good choice for neurosurgeons to manage these giant tumors in the sacral region.

Cervical Primary Ewing's Sarcoma in Intradural and Extramedullary Location and Skip Metastasis to Cauda Equina.

Ewing's Sarcoma (ES) is a rare malignant tumor that commonly arises from skeletal bone but rarely has an extraskeletal origin. Intradural ES is rare in childhood and adulthood. Intradural metastasis is very rarely encountered in clinical observations. There are only two reports of intradural ES skip metastasis in the literature to date. Here we present the case of a 39-year-old female who was admitted to our hospital with complaints of left upper limb pain and numbness for one year. Cervical magnetic resonance imaging showed a C4-C6 primary intradural and extramedullary Ewing's sarcoma. Skip metastasis to cauda equina was observed three years following the first surgery and chemoradiotherapy.

Detection of Candida albicans Sap2 in cancer patient serum samples by an indirect competitive enzyme-linked immunosorbent assay for the diagnosis of candidiasis.

BACKGROUND: The secreted aspartyl proteinases 2 (Sap2) of Candida albicans (C. albicans) is a potential marker of candididasis. It is a virulence factor associated with adherence and tissue invasion. AIM: In order to detect Sap2 in clinical sera, we developed an indirect competitive enzyme-linked immunosorbent assay (ELISA). MATERIALS AND METHODS: Polyclonal antibodies were produced for Sap2 by injecting Sap2 into a New Zealand White inbred rabbit. They could be used at a dilution exceeding 1:1200 in an indirect ELISA, and detected Sap2 concentration up to 1 ng/mL. RESULTS: Of the 286 cancer serum samples tested, 16.8% were found as candidiasis. The test was simple and economical to perform and had a level of sensitivity for detection of low-titer positive sera; thus, it may be proven to be of value in epidemiological studies on candidiasis.

Endostatin gene therapy for endometriosis in rats.

OBJECTIVE: Endostatin gene therapy for endometriosis was studied in an experimental autotransplantation model in rats. METHODS: Endometriotic lesions were transfected by intralesional injection of the plasmid lipofectamine-endostatin-pBud (group 1), lipofectamine-pBud (empty vector; group 2) or phosphate-buffered saline (group 3). Endostatin mRNA and protein levels in lesions were evaluated by quantitative real-time reverse transcription-polymerase chain reaction and Western blot analysis. Endostatin and vascular endothelial growth factor (VEGF) protein levels in serum, and microvessel density (MVD) and matrix metalloproteinase (MMP)-2 protein levels in endometriotic lesions, were also determined. RESULTS: Lipofectamine-endostatin-pBud injection increased endostatin mRNA and protein levels in lesions. Lesions were significantly smaller, and serum VEGF levels significantly lower, in group 1 versus controls. Serum VEGF was significantly and negatively correlated with serum endostatin. In group 1, MMP-2 levels and MVD were significantly lower versus controls. MMP-2 level was negatively correlated with endostatin. CONCLUSIONS: Gene therapy with endostatin appears to be an effective treatment for endometriosis. Restoration of endostatin gene expression by gene transfer in vivo might be a potential gene therapy approach for human endometriosis.

Inhibition of histone deacetylase-induced myocardial repair is mediated by c-kit in infarcted hearts.

Histone deacetylases (HDACs) play a critical role in the regulation of gene transcription, cardiac development, and diseases. The aim of this study was to test whether inhibition of HDACs induces myocardial repair and cardiac function restoration through c-kit signaling in mouse myocardial infarction models. Myocardial infarction in wild type Kit(+/+) and Kit(W)/Kit(W-v) mice was created following thoracotomy by applying permanent ligation to the left anterior descending artery. The HDAC inhibitor, trichostatin A (TSA, 0.1 mg/kg), was intraperitoneally injected daily for a consecutive 8 weeks after myocardial infarction. 5-Bromo-2-deoxyuridine (BrdU, 50 mg/kg) was intraperitoneally delivered every other day to pulse-chase label in vivo endogenous cardiac replication. Eight weeks later, inhibition of HDACs in vivo resulted in an improvement in ventricular functional recovery and the prevention of myocardial remodeling in Kit(+/+) mice, which was eliminated in Kit(W)/Kit(W-v) mice. HDAC inhibition promoted cardiac repairs and neovascularization in the infarcted myocardium, which were absent in Kit(W)/Kit(W-v) mice. Re-introduction of TSA-treated wild type c-kit(+) CSCs into Kit(W)/Kit(W-v) myocardial infarction heart restored myocardial functional improvement and cardiac repair. To further validate that HDAC inhibition stimulates c-kit(+) cardiac stem cells (CSCs) to facilitate myocardial repair, GFP(+) c-kit(+) CSCs were preconditioned with TSA (50 nmol/liter) for 24 h and re-introduced into infarcted hearts for 2 weeks. Preconditioning of c-kit(+) CSCs via HDAC inhibition with trichostatin A significantly increased c-kit(+) CSC-derived myocytes and microvessels and enhanced functional recovery in myocardial infarction hearts in vivo. Our results provide evidence that HDAC inhibition promotes myocardial repair and prevents cardiac remodeling, which is dependent upon c-kit signaling.

Correlation between surgical modality and clinicopathologic characteristics for ureteral transitional cell carcinoma.

PURPOSE: To investigate the relationship between surgical modality and clinicopathologic features for ureteral transitional cell carcinoma. METHODS: The correlation between surgical modality and clinicopathology characteristics of 146 patients with ureteral carcinoma having undergone surgery was evaluated using univariate analysis by a general linear model. RESULTS: 43.8%, 51.4% and 4.8% of patients experienced nephroureterectomy, renal conservation management and palliative operations, respectively, with a mean survival time of 97.3, 101.3 and 51.0 months (p=0.069) accordingly. Univariate analysis by general linear model indicated that the size of lesions, pathologic stage and tumour grade had a statistically significant impact on surgical modality (p=0.000, p=0.001 and p=0.017, respectively). CONCLUSION: Tumour stage and grade, as well as tumour size, correlate with surgical modality.

Correlation between surgical modality and clinicopathologic characteristics for ureteral transitional cell carcinoma

PURPOSE: To investigate the relationship between surgical modality and clinicopathologic features for ureteral transitional cell carcinoma. METHODS: The correlation between surgical modality and clinicopathology characteristics of 146 patients with ureteral carcinoma having undergone surgery was evaluated using univariate analysis by a general linear model. RESULTS: 43.8%, 51.4% and 4.8% of patients experienced nephroureterectomy, renal conservation management and palliative operations, respectively, with a mean survival time of 97.3, 101.3 and 51.0 months (p=0.069) accordingly. Univariate analysis by general linear model indicated that the size of lesions, pathologic stage and tumour grade had a statistically significant impact on surgical modality (p=0.000, p=0.001 and p=0.017, respectively). CONCLUSION: Tumour stage and grade, as well as tumour size, correlate with surgical modality (AU)

Angiotensin receptor blockers improve insulin resistance in type 2 diabetic rats by modulating adipose tissue.

Adipose tissue is recognized as a pivotal organ in the development of insulin resistance. This study seeks to determine the effect of angiotensin receptor blockade (ARB) on insulin resistance of adipocytes in culture and in a rat model of type 2 diabetes. Treatment of Otsuka Long-Evans Tokushima Fatty rats with the ARB L158809 for six months significantly lowered fasting plasma glucose, cholesterol and triglyceride levels but led to higher plasma adiponectin levels. Insulin resistance, measured by an intraperitoneal glucose tolerance test, of the treated rats was significantly improved along with an increase in the number of small differentiated adipocytes; however, epididymal fat mass decreased. Treatment significantly lowered lipid peroxidation and MCP-1 expression while increasing adiponectin production by the adipose tissue. ARB treatment significantly improved insulin sensitivity and markedly suppressed AT2-induced oxidative stress, PAI-1 and MCP-1 levels and NF-kappaB activation of adipocytes in culture. Treatment increased adiponectin and PPARgamma expression along with intracellular triglyceride levels reflecting differentiation of the cultured adipocytes. Our study suggests that ARB treatment improves insulin resistance by modification of adipose tissue thereby blunting the development of diabetes.

Effective matching in a nonlinear directional coupler with waveguide mismatching and nonuniform nonlinearity.

A variable-coupling-coefficient nonlinear directional coupler with mismatching and nonuniformity is studied by means of coupled mode equations with effective mismatching. It is pointed out that the effective mismatching can be cancelled out for any given input power by properly adjusting the magnitudes of the mismatching and nonuniformity. Numerical examples are given to show that complete power transfer between two waveguides can be achieved for a mismatched and nonuniform nonlinear directional coupler and for a Gaussian as well as an exponential variable-coupling-coefficient nonlinear directional coupler.

Variable coupling coefficient nonlinear directional couplers with self-focusing and self-defocusing nonlinearity.

Nonlinear directional couplers (NLDCs) with a variable coupling coefficient (VCC) in self-focusing and self-defocusing materials are investigated. Specifically, the Gaussian type VCC NLDCs are studied in detail. The results show that the responses of the VCC NLDCs on self-focusing and self-defocusing materials are different, especially when input power is high. The coupled-mode theory can also be used to predict the characteristics of the VCC NLDC on self-focusing material, even when input power is high.

Arc-shaped waveguide switch based on the third-order nonlinear effect.

A kind of arc-shaped all-optical waveguide switch is proposed for the first time, to the best of our knowledge, and the switching characteristics of it are investigated by means of the beam propagation method. The effects of saturation and loss on the characteristics of the switch are discussed.

Evolutionarily stable strategy, stable state, periodic cycle and chaos in a simple discrete time two-phenotype model.

A simple discrete time two-phenotype matrix game model is investigated. In this model, according to the suggestion of Vincent & Fisher (1988, Evolutionary Ecology 2, 321-337), the fitness of an individual is defined to be an exponential function of its expected pay-off value. The results show that : (i) in our model, the static conditions of ESS are only dependent on the properties of pay-off matrix, but not on the specific form of fitness function. This result implies that the ESS conditions on our model are completely identical with the conditions in the two-phenotype model with linear fitness function. (ii) In our model, the relationship between the static conditions of ESS and the dynamic properties of the pure strategy model is that if the interior fixed point of the pure strategy model is not an ESS-equilibrium, then it must be unstable; conversely, if the interior fixed point of the pure strategy model is an ESS-equilibrium, then it can be stable or unstable, and an unstable ESS-equilibrium must correspond to the cyclic or chaotic behaviour of the population state.

CRP:cAMP complex binding to the lac operator region induces a structural change in lac DNA.

Changes in DNA structure induced by cAMP receptor protein (CRP) binding to the lac-control region contained on a 231 bp fragment were investigated by measurement of the molar cyclization factor (jM). Increases in jM were observed at low to moderate CRP: cAMP complex concentrations and correlated with CRP binding to the promoter-proximal CRP binding site. At CRP:cAMP complex concentrations greater than 200 nM, decreases in jM correlated with CRP binding to both the promoter-proximal and the operator-proximal CRP binding sites. These results show that binding of the CRP:cAMP complex to the operator-proximal CRP binding site induces a structural change in lac DNA.

Granulocyte-macrophage colony-stimulating factor regulates the functional adhesive state of very late antigen-4 expressed by eosinophils.

As very late antigen-4 (VLA-4) can exist in different functional states, we have sought to determine whether a cytokine expressed by inflamed endothelium (i.e., granulocyte-macrophage CSF (GM-CSF)) could regulate the functional state of VLA-4 expressed by eosinophils. Using a micropipette single cell adhesion assay able to measure the strength of adhesion forces, eosinophils exhibited low levels of basal adhesion to unstimulated endothelium (separation force, 0.022 +/- 0.003 mdynes). In contrast, individual eosinophils bound to IL-1beta-stimulated endothelium (0.49 +/- 0.02 mdynes), TNF-stimulated endothelium (0.62 +/- 0.05 mdynes), or IL-4-stimulated endothelium (0.11 +/- 0.01 mdynes) with increased avidity as assessed by separation force. Eosinophil binding to IL-4-stimulated endothelium was significantly inhibited by neutralizing Abs to either vascular cell adhesion molecule (VCAM) or VLA-4. The strength of eosinophil adhesion to VCAM (0.31 +/- 0.02 mdynes) or to connecting segment-1 (CS-1) (0.18 mdynes) was greater than the strength of eosinophil adhesion to unstimulated endothelium (0.02 mdynes), but was less than the strength of eosinophil adhesion to IL-1beta-stimulated endothelium (0.49 +/- 0.02 mdynes). After incubating eosinophils for 30 min with GM-CSF, the mean adhesion strength of eosinophils to CS-1 and VCAM increased significantly by 84 and 54%, respectively, compared with that of controls. This increased binding of eosinophils to VCAM or CS-1 was not due to alterations in VLA-4 receptor number (assessed by FACS analysis) or alterations in VLA-4 receptor distribution (assessed by confocal microscopy). These studies suggest that endothelial-derived cytokines such as GM-CSF have the potential to alter the functional state of eosinophil-expressed VLA-4 from a low affinity state to a high affinity state.

Functional roles of in vivo footprinted DNA motifs within an alpha-globin enhancer. Erythroid lineage and developmental stage specificities.

Transcriptional regulation of the human alpha-like globin genes, embryonic zeta 2 and adult alpha, during erythroid development is mediated by a distal enhancer, HS-40. Previous protein-DNA binding studies have shown that HS-40 consists of multiple nuclear factor binding motifs that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner. We have systematically analyzed the functional roles of these factor binding motifs of HS-40 by site-directed mutagenesis and transient expression assay in erythroid cell cultures. Three of these HS-40 enhancer motifs, 5'NF-E2/AP1, GT II, and GATA-1(c), positively regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562 cells and the adult alpha-globin promoter activity in adult erythroid MEL cells. On the other hand, the 3'NF-E2/AP1 motif is able to exert both positive and negative regulatory effects on the zeta 2-globin promoter activity in K562 cells, and this dual function appears to be modulated through differential binding of the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor. Mutation in the GATA-1(d) motif, which exhibits an adult erythroid-specific genomic footprint, decreases the HS-40 enhancer function in dimethyl sulfoxide-induced MEL cells but not in K562 cells. These studies have defined the regulatory roles of the different HS-40 motifs. The remarkable correlation between genomic footprinting data and the mutagenesis results also suggests that the erythroid lineage- and developmental stage-specific regulation of human alpha-like globin promoters is indeed modulated by stable binding of specific nuclear factors in vivo.

Tetrandrine, a Ca++ antagonist: effects and mechanisms of action in vascular smooth muscle cells.

Tetrandrine, an alkaloid extracted from the Chinese medicinal herb Radix stephania tetrandrae, has traditionally been used to treat hypertension. In the present study, the effect of tetrandrine on vascular smooth muscle was investigated by using the rat tail artery as a model of a resistance vessel. Tetrandrine relaxes the tension in tail artery helical strips produced by depolarization with 60 mM KCl. Further studies show that tetrandrine inhibits the KCl-induced intracellular Ca++ increase and L-type voltage-dependent Ca++ channel currents, suggesting that tetrandrine relaxes the vessel via inhibition of Ca++ influx through Ca++ channels. Tetrandrine also inhibits norepinephrine (NE)-induced vasocontraction in the presence of extracellular Ca++. It does not, however, inhibit NE-induced vasocontraction in the absence of extracellular Ca++. Tetrandrine also inhibits the NE-induced intracellular Ca++ increase in the presence of extracellular Ca++ and has no effect on the NE-induced intracellular Ca++ increase in the absence of extracellular Ca++. This suggests that tetrandrine also blocks NE-induced Ca++ influx but not NE-induced Ca++ release from the intracellular Ca++ stores. Furthermore, tetrandrine inhibits thapsigargin-induced intracellular Ca++ concentration increase, suggesting that, in addition to blocking Ca++ influx, tetrandrine also may interfere with the interaction between thapsigargin and Ca++ adenosine triphosphatase.

Syndrome of endemic arsenism and fluorosis. A clinical study.

Sixty-five patients in Xinjiang with syndrome of endemic arsenism and fluorosis (SEAF) were investigated clinically from March 1982 to August 1989. SEAF is a kind of chronic syndrome resulting from the combined, harmful effects of two trace elements, arsenic and fluorine. Peripheral neuritis and cardiovascular changes were observed in this syndrome more often than in simple arsenism or simple fluorosis. The excessive quantities of these two trace elements in blood might have a synergic, harmful effect on the nervous and circulatory systems. No definite conclusion could be reached with regard to the morbidity of skin and visceral tumors in this series. The incidence of associated skin cancer was found to be 7.7% and an associated Grade II squamous cell carcinoma of the esophagus was encountered in one patient.

Electrophysiological effects of cimetidine on rabbit myocardium.

Effects of cimetidine (Cim) were studied electrophysiologically on fast action potential (AP) in rabbit papillary muscle and slow AP in pacemaker cell of rabbit sinoatrial node (SAN) as well as on atrioventricular (A-V) conduction in anesthetized rabbit. Cim (0.01, 0.1, 1, and 2 mmol.L-1) induced prolongations of AP duration (APD) and effective refractory period (ERP), slowing down of the maximal rate of rise of phase 0 (Vmax) and of the slope of phase 4 depolarization (SP4), and a decrease of AP amplitude (APA) in concentration-dependent manners. Cim (100 mg.kg-1 iv) prolonged the A-V conduction. The results suggest that Cim, like quinidine, shows a membrane stabilizing effect, which may be the electrophysiological basis of the anti-arrhythmic effect of Cim.