Pituitary metastasis: From pathology to clinical and radiological considerations.

PURPOSE: A review of the literature with respect to pituitary metastases (PM) with clinical and radiological considerations are summarized to facilitate clinical decision making in the management of PM METHODS: A review of literature associated with PM and tumour to tumour metastases in the English literature was reviewed and summarized RESULTS: Pituitary metastases account for 1.0-3.6% of all surgically treated pituitary lesions. Often identified in parallel with extensive disseminated disease, once diagnosed, the prognosis is generally poor, although survival is highly heterogeneous and dependent on the primary tumor histology. Within this anatomical region is also the observation of tumor-to-tumor metastases and collision tumours. Both the tumor macro- and microenvironment play central roles to the progression of disease with distinctive radiological features that may suggest a metastatic sellar lesion as opposed to a primary pituitary lesion. Surgical resection is the first line of therapy followed by adjuvant chemoradiotherapy and endocrinological evaluation for hormonal supplementation CONCLUSION: PMs are relatively rare but important oncological entities representing disseminated disease in the majority of cases. Careful consideration of the relevant clinical history and radiological features can aid the clinician differentiate between a metastatic lesion to the pituitary region and a primary pituitary tumor. While surgical resection is first line therapy, stereotactic radiosurgery in carefully selected patients is emerging as a viable alternative.

[Application of failure mode and effect analysis in reducing the risk of nosocomial infection].

Objective: To explore the effect of failure mode and effect analysis (FMEA) in the management of nosocomial infection, and provide reference for the effective prevention and control of nosocomial infection. Methods: Using FMEA to identify, analyze, evaluate and screen out the high-risk events of nosocomial infection in January 2020, from which two hospital level priority improvement projects of hand hygiene compliance and blood-borne occupational exposure were determined. After risk control and intervention measures, the effects before and after improvement were compared. Results: Except for the lack of incentive mechanism and insufficient communication between medical and nursing teams, the differences in hand hygiene compliance and blood-borne occupational exposure risk priority coefficients before and after the implementation of FMEA were statistically significant (P<0.05) . After the implementation of FMEA, the hand hygiene compliance was 74.92% (79375/105953) , which was significantly higher than 68.40% (58361/85328) before the implementation of FMEA, and the difference was statistically significant (χ(2)=996.55, P<0.01) . The incidence of blood-borne occupational exposure after the implementation of FMEA was 3.85% (80/2080) , which was lower than the 6.16% (123/1998) before the implementation of FMEA, and the difference was statistically significant (χ(2)=11.49, P<0.01) . Conclusion: FMEA has a good effect in nosocomial infection management. It can identify and evaluate the risk of nosocomial infection prospectively, so as to control the risk effectively.

The Pituitary Tumors and Their Tumor-Specific Microenvironment.

Pituitary tumors develop within a macroenvironment and microenvironment that favor their overall survival. Given the pituitary gland's unique anatomic, histological, and physiological properties, the role of the TME in the pituitary tumors is central. This chapter summarizes the body of literature investigating the role of each component of the TME in relation to tumors of the pituitary and its intimate association with tumorigenesis, maintenance, and progression.

[Investigation and analysis of tinnitus in diabetic patients].

Objective:To analyze the influencing factors of tinnitus in diabetic patients and the correlation between hearing loss and tinnitus.Method:Participants were patients with diabetes. Subjects were tested for hearing function and tinnitus symptoms by questionnaire and pure tone audiometry.Result:①112 patients (55 were men and 57 were women) were affected by tinnitus symptoms in 255 patients with diabetes，there were no significant differences between the number of male patients and female patients(P=0.278).②The incidence of tinnitus increased with age (≤30 year: 40%, 31-40 year :25%, 41-50 year: 27%, 51-60 year: 43%, >60 year: 55%),and there was significant differences in the number of patients among different age (P=0.001).③The incidence of tinnitus was no significant difference in diabetes patients with different educational level (P=0.648).④Totally 83 subjects who complained hearing impairment were tested for hearing loss by pure tone audiometry, while 113 (66%) of 172 subjects who insisted their hearing were normal had hearing loss. Of the subjects with normal hearing but tinnitus, 72% had hearing loss and 62% of patients without tinnitus actually had hearing loss.⑤There were statistically significant in patients with diabetes between the incidence of tinnitus and low/intermediate frequency hearing loss or high frequency hearing loss.Conclusion:The incidence of tinnitus symptoms is increased in patients with diabetes mellitus, which may be related to the age, the incidence of hearing loss,however, may be irrelevant to gender and educational level. Diabetic patients with tinnitus symptoms should be tested as soon as possible to achieve early intervention.

Population pharmacokinetics and Bayesian estimation of tacrolimus exposure in Chinese liver transplant patients.

WHAT IS KNOWN AND OBJECTIVES: Tacrolimus (TAC) is widely used as part of immunosuppressive regimens. There is great interindividual variation on the disposition of TAC. The aim of this study was to develop a population pharmacokinetic (PPK) model for Chinese liver transplant patients and evaluate genetic polymorphism and other possible factors on the PK parameters. The exposure of TAC is to be estimated through Bayesian modelling. METHODS: A total of 47 sets of rich-time PK and 1234 conventional therapeutic drug monitoring (TDM) data were collected from 125 Chinese liver transplant patients. The pathophysiological data of these patients were recorded. CYP3A5*3 and ABCB1 genotypes were determined for each patient. The PPK model for TAC was established by nonlinear mixed-effects modelling (nonmem). The impact of pathophysiology and genotype on PPK parameters was evaluated. Bayesian estimators for the area under concentration-time curve (AUC) of TAC were validated. RESULTS: A two-compartment model with lag time was found to be the most suitable model for the pooled full PK and TDM data for Chinese liver transplant patients. The CL/F, V2 /F, Q/F, V3 /F, Ka and lag time were 17.4±0.81 L/h, 165±44.1 L, 54.9±25.8L/h, 594±87.5 L, 0.51±0.095 L/h and 1.57±0.34 h. Post-operative day (POD), creatinine clearance (CLcr) and ABCB1 C3435T genotypes were found to have significant influences on CL/F (P<.01). ABCB1 C3435T genotypes showed a significant correlation with V2 /F (P<.01). C0 -C2 and C0 -C2 -C4 were shown to be suitable for the estimation of AUC in Chinese liver transplant patients. WHAT IS NEW AND CONCLUSION: A PPK model for TAC was established successfully in Chinese liver transplant patients. POD, CLcr and ABCB1 C3435T genotypes were shown to have significant effects on CL/F. The AUC of TAC in Chinese liver transplant patients could be estimated through Bayesian modelling, based on which individualized immunosuppressive regimens can be designed.

Quantum Spin Hall Effect and Tunable Spin Transport in As-Graphane.

Tunable spin transport in nanodevices is highly desirable to spintronics. Here, we predict existence of quantum spin Hall effects and tunable spin transport in As-graphane, based on first-principle density functional theory and tight binding calculations. Monolayer As-graphane is constituted by using As adsorbing on graphane with honeycomb H vacancies. Owing to the surface strain, monolayer As-graphane nanoribbons will self-bend toward the graphane side. The naturally curved As-graphane nanoribbons then exhibit unique spin transport properties, distinctively different from the flat ones, which is a two-dimensional topological insulator. Under external stress, one can realize tunable spin transport in curved As-graphane nanoribon arrays. Such intriguing mechanical bending induced spin flips can offer promising applications in the future nanospintronics devices.

Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis.

Microbial communities reside in healthy tissues but are often disrupted during disease. Bacterial genomes and proteins are detected in brains from humans, nonhuman primates, rodents and other species in the absence of neurological disease. We investigated the composition and abundance of microbiota in frozen and fixed autopsied brain samples from patients with multiple sclerosis (MS) and age- and sex-matched nonMS patients as controls, using neuropathological, molecular and bioinformatics tools. 16s rRNA sequencing revealed Proteobacteria to be the dominant phylum with restricted diversity in cerebral white matter (WM) from MS compared to nonMS patients. Both clinical groups displayed 1,200-1,400 bacterial genomes/cm3 and low bacterial rRNA:rDNA ratios in WM. RNAseq analyses showed a predominance of Proteobacteria in progressive MS patients' WM, associated with increased inflammatory gene expression, relative to a broader range of bacterial phyla in relapsing-remitting MS patients' WM. Although bacterial peptidoglycan (PGN) and RNA polymerase beta subunit immunoreactivities were observed in all patients, PGN immunodetection was correlated with demyelination and neuroinflammation in MS brains. Principal component analysis revealed that demyelination, PGN and inflammatory gene expression accounted for 86% of the observed variance. Thus, inflammatory demyelination is linked to an organ-specific dysbiosis in MS that could contribute to underlying disease mechanisms.

GABA transport and neuroinflammation are coupled in multiple sclerosis: regulation of the GABA transporter-2 by ganaxolone.

Interactions between neurotransmitters and the immune system represent new prospects for understanding neuroinflammation and associated neurological disease. GABA is the chief inhibitory neurotransmitter but its actions on immune pathways in the brain are unclear. In the present study, we investigated GABAergic transport in conjunction with neuroinflammation in models of multiple sclerosis (MS). Protein and mRNA levels of γ-amino butyric acid transporter 2 (GAT-2) were examined in cerebral white matter from MS and control (Non-MS) patients, in cultured human macrophages, microglia and astrocytes, and in spinal cords from mice with and without experimental autoimmune encephalomyelitis (EAE) using western blotting, immunocytochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). GABA levels were measured by HPLC. The GAT-2's expression was increased in MS patients' (n=6) white matter, particularly in macrophage lineage cells, compared to Non-MS patients (n=6) (p<0.05). Interferon-γ (IFN-γ) stimulation of human macrophage lineage cells induced GAT-2 expression and reduced extracellular GABA levels (p<0.05) but soluble GABA treatment suppressed HLA-DRα, GAT-2 and XBP-1/s expression in stimulated macrophage lineage cells (p<0.05). Similarly, the synthetic allopregnanolone analog, ganaxolone (GNX), repressed GAT-2, JAK-1 and STAT-1 expression in activated macrophage lineage cells (p<0.05). In vivo GNX treatment reduced Gat-2, Cd3ε, MhcII, and Xbp-1/s expression in spinal cords following EAE induction (p<0.05), which was correlated with improved neurobehavioral outcomes and reduced neuroinflammation, demyelination and axonal injury. These findings highlight altered GABAergic transport through GAT-2 induction during neuroinflammation. GABA transport and neuroinflammation are closely coupled but regulated by GNX, pointing to GABAergic pathways as therapeutic targets in neuroinflammatory diseases.

Analysis of the economic burden of diagnosis and treatment of tuberculosis patients in rural China.

SETTING: A county in Jiangsu Province, China. OBJECTIVES: To estimate the costs of the diagnosis and treatment of tuberculosis (TB) from the patient's perspective and to identify determinants of the patient's financial burden. DESIGN: In a cross-sectional survey, we interviewed 316 patients diagnosed from January 2010 to May 2011 who had already completed their anti-tuberculosis treatment. The financial burden on TB patients included out-of-pocket costs and productivity losses. RESULTS: The average per capita total out-of-pocket cost was 3024.0 Chinese yuan (CNY), with a median cost of 1086 CNY (interquartile range [IQR] 480-2456). Mean out-of-pocket medical and non-medical costs were respectively 2565.7 CNY and 458.3 CNY. Productivity lost by patients and family members was 2615.2 CNY (median 500, IQR 250-2025). Factors associated with out-of-pocket costs and productivity losses included hospitalisation, adverse drug reactions, cost of drugs to 'protect' the liver, cost of second-line anti-tuberculosis drugs and diagnostic delay. CONCLUSION: Although the government of China has implemented a 'free TB service policy', the economic burden on patients is still heavy. More patient-centred interventions are essential to reduce the financial burden on patients.

Establishment of a visualized nude mouse model of cervical carcinoma with high potential of lymph node metastasis via total orthotopic transplantation.

OBJECTIVE: To screen cervical carcinoma (CC) SiHa subgroups with high potential of lymphatic metastasis and establish a visualized nude mouse model of cervical carcinoma with a total orthotopic transplantation approach. METHODS: A cervical carcinoma SiHa subgroup with high potential of lymphatic metastasis was isolated by in vitro and in vivo primary culture and continuous passage screening of cervical carcinoma SiHa cells that stably expressed enhanced green fluorescent protein (EGFP). Forty male nude mice aged 6-8 weeks were equally randomized to group A receiving unscreened SiHa/EGFP cells, and group B received in vitro and in vivo screened SiHa/EGFP cells with high potential of lymph node metastasis. RESULTS: In the 20 animals of group A receiving orthotopic transplantation of unscreened SiHa/EGFP cells, the primary tumors were small; local lymph node metastasis was observed in five animals; local organ invasion and distal lymph node metastasis were observed in two animals; and no lung metastasis was observed. In the 20 animals of group B receiving screened SiHa/EGFP cells, local lymph node metastasis occurred in all animals; distal lymph node metastasis was observed in 18 animals; and lung metastasis was observed in seven animals. CONCLUSION: A cervical carcinoma SiHa subgroup with high potential of lymphatic metastasis was isolated and a visualized nude mouse model of cervical carcinoma with high potential of lymph node metastasis was established through total orthotopic transplantation successfully. This provided a good platform for the further study of cervical carcinoma-related mechanisms, especially mechanisms of lymphatic metastasis in cervical carcinoma.

Electrical performances and structural designs of copper bonding in wafer-level three-dimensional integration.

The integrity of bonded Cu interconnects in wafer-level three-dimensional integration has been investigated as the function of pattern size and density, as well as bonding process parameter. The desired pattern density coupled with the application of bonding process profile we developed gives optimal yield and alignment accuracy, and provides excellent electrical connectivity and contact resistance through the entire wafer. This result is a key milestone in establishing the manufacturability of Cu-based interconnections for 3D integration technology.

Fabrication of nano-scale Cu bond pads with seal design in 3D integration applications.

A method to fabricate nano-scale Cu bond pads for improving bonding quality in 3D integration applications is reported. The effect of Cu bonding quality on inter-level via structural reliability for 3D integration applications is investigated. We developed a Cu nano-scale-height bond pad structure and fabrication process for improved bonding quality by recessing oxides using a combination of SiO2 CMP process and dilute HF wet etching. In addition, in order to achieve improved wafer-level bonding, we introduced a seal design concept that prevents corrosion and provides extra mechanical support. Demonstrations of these concepts and processes provide the feasibility of reliable nano-scale 3D integration applications.

Observation of fluorescence emissions from single-bubble sonoluminescence in water doped with quinine.

Sonoluminescence is a phenomenon involving the transduction of sound into light. The detailed mechanism as well as the energy-focusing potentials are not yet fully explored and understood. So far only optical photons are observed, while emissions in the ultra-violet range are only inferred. By doping the fluorescent dye quinine into water with dilute sulphuric acid, the high energy photons can be converted into the optical photons with slower decay constants. These sonoluminescence and fluorescent emissions were observed in coincidence, and the emitted signals of the two modes can be differentiated by their respective timing profiles. Plans for using this technique as a diagnostic tool to quantitatively study ultra-violet and other high energy emissions in sonoluminescence are discussed.

Radiation dosimetry estimates for the PET serotonin transporter probe 11C-DASB determined from whole-body imaging in non-human primates.

The radiotracer 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile labelled in the N-methyl position (11C-DASB) is a selective radioligand for the in vivo quantification of serotonin transporters (SERTs) using positron emission tomography (PET). The current study quantified the distribution of activity in two rhesus monkeys after the injection of approximately 333 MBq (9 mCi) 11C-DASB. Whole-body images were acquired at 22 time points for a total of 120 min following injection of the radioligand. Source organs were identified at each time point from both tomographic images (using multiple regions of interest on each tomograph for each organ) and a single planar image (using a single region of interest for each organ). The peak activities in planar images in the five identified source organs (expressed as per cent injected dose (ID)) were lungs (24% ID at 1.5 min), kidneys (6.5% ID at 4 min), liver (8% ID at 3 min), brain (4% ID at 5 min) and spleen (0.42% ID at 3 min). Mono-exponential fitting of activity overlying the bladder suggested that approximately 14% of activity was excreted via the urine. The radiation burden to the body was calculated from residence times of these source organs and then scaled to corresponding human values. The calculated effective dose from tomographic and planar images was 6.0 and 6.4 microGy x MBq(-1) (22.3 and 23.7 mrad x mCi(-1)), respectively. The planar analysis was much easier to perform, and generally yielded slightly higher (i.e., more conservative) estimates of radiation burden than the tomographic analysis. The estimated radiation burden of 11C-DASB is relatively modest and would allow multiple scans per research subject per year.

Somatostatin modulates the behavioral effects of dopamine receptor activation in parkinsonian rats.

Somatostatin may play a role in several neuropsychiatric disorders, including Parkinson's disease. Although functional interactions between somatostatinergic and dopaminergic transmitter systems have been well documented, no study has been conducted in animals with experimental Parkinsonism to explore the effects of somatostatin on dopamine receptor-mediated behavior. In the present study, rats with unilateral 6-hydroxydopamine-induced destruction of the medial forebrain bundle were assessed following administration of the dopamine(1/2) receptor agonist apomorphine. Ipsilateral intrastriatal infusion of somatostatin produced a dose-related inhibition of apomorphine-induced rotations with maximal effect at a dose of 7.5 microg in 2 microl. This inhibitory effect of somatostatin was antagonized by the somatostatin antagonist cyclo-somatostatin (0.1 microg in 2 microl, intrastriatally). Neither somatostatin (up to 15 microg in 2 microl) nor cyclo-somatostatin on its own induced rotations; similarly, this dose of cyclo-somatostatin did not affect apomorphine-induced rotations. From these results we suggest that exogenous somatostatin, by directly acting on its specific receptors in the striatum, inhibits the effects of dopamine receptor activation in parkinsonian rats. We conclude that therapies based on modulation of somatostatin may be worth exploring in the management of Parkinson's disease and other disorders of the basal ganglia.

Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover.

Motor fluctuations are a major disabling complication in the treatment of Parkinson's disease. To investigate whether such oscillations in mobility can be attributed to changes in the synaptic levels of dopamine, we studied prospectively patients in the early stages of Parkinson's disease with a follow-up after at least 3 years of levodopa treatment. At baseline, 3 positron emission tomography (PET) scans using [11C]raclopride before and after (1 hour and 4 hours) orally administered levodopa were performed on the same day for each patient. Patients who developed "wearing-off" fluctuations during the follow-up period had a different pattern of levodopa-induced changes in [11C]raclopride binding potential (BP) from that observed in patients who were still stable by the end of the follow-up. Thus, 1 hour post-levodopa the estimated increase in the synaptic level of dopamine was 3 times higher in fluctuators than in stable responders. By contrast, only stable responders maintained increased levels of synaptic dopamine in the PET scan performed after 4 hours. These results indicate that fluctuations in the synaptic concentration of dopamine precede clinically apparent "wearing-off" phenomena. The rapid increase in synaptic levels of dopamine observed in fluctuators suggests that increased dopamine turnover might play a relevant role in levodopa-related motor complications.

Optical properties of porcine skin dermis between 900 nm and 1500 nm.

The weak absorption of shortwave infrared light by skin tissues between 700 and 1500 nm offers an important window for diagnosis by optical means. The strong scattering of shortwave infrared light by the skin, however, presents a challenge to the modelling of light propagation through the skin and the understanding of skin optics. We have measured the collimated and diffuse transmittance and diffuse reflectance of porcine skin dermis samples within 30 h post-mortem. Monte Carlo simulations have been performed to inversely determine the absorption coefficient, scattering coefficient and anisotropy factor of the dermis samples in the spectral range from 900 to 1500 nm. We further analyse the sensitivity of the values of the parameters to the experimental errors and inverse calculation procedures. The state of the cellular integrity of the skin samples following optical measurements was verified using transmission electron microscopy. These results were correlated to study post-mortem effects on the in vitro optical properties of porcine dermis. We concluded that for samples stored within crushed ice for up to 30 h post-mortem the wavelength dependence of optical properties of the dermis remains unchanged while the values of the parameters vary moderately due to modification of the water content of the tissue.

Modeling of the rough-interface effect on a converging light beam propagating in a skin tissue phantom.

Light distribution in a strong turbid medium such as skin tissue depends on both the bulk optical properties and the profiles of the interfaces where mismatch in the refractive index occurs. We present recent results of a numerical investigation on the light distribution inside a human skin tissue phantom for a converging laser beam with a wavelength near 1 mum and its dependence on the roughness of the interfaces and index mismatch. The skin tissue is modeled by a two-layer structure, and within each layer the tissue is considered macroscopically homogeneous. The two interfaces that separate the epidermis from the ambient medium and the dermis are considered randomly rough. With a recently developed method of Monte Carlo simulation capable of treating inhomogeneous boundary conditions, light distributions in various cases of interface roughness and index mismatch are obtained, and their relevance to the measurements of optical parameters of the skin tissue and laser surgery under the skin surface are discussed.

HPV6b virus like particles are potent immunogens without adjuvant in man.

Subjects with genital warts were immunized three times or more with HPV6b VLPs without adjuvant. All immunized subjects had DTH to HPV6b L1 protein. Of 32 subjects, nine had HPV6b specific antibody prior to immunization and 22 acquired antibody with immunization. VLP specific antibody increased following a single immunization in 6 of 8 subjects with low level antibody at recruitment. Complete regression of genital warts was observed in 25 of 33 evaluable subjects over the 20-week observation period. We conclude that immunization with HPV6b L1 VLPs without adjuvant induces immunity to the L1 protein epitopes recognised during natural infection, and may accelerate regression of warts.

Alterations of T-lymphocyte subsets, soluble IL-2 receptor, and IgE in peripheral blood of children with acute asthma attacks.

BACKGROUND: T-cell activation and alteration of cytokines are involved in the pathogenesis of atopic asthma. However, the profile of circulating T-lymphocyte subsets, related cytokines, and plasma IgE during acute asthma attacks is still unclear. OBJECTIVE: In an attempt to illustrate the dynamics of these parameters in asthma attacks, we investigated the changes of T-cell subsets, lymphocyte activation, soluble IL-2R, and IgE in peripheral blood in children during and after acute asthma attacks. METHODS: This study was carried out in a cohort of Chinese children (n = 59) with acute asthma attacks. Immunoassays were performed when the patients had acute attacks before treatment, and the patients were reexamined in the 4 weeks after the resolution of acute attacks with therapy. Paired t tests were used for the statistical analysis of these patients to compare the data obtained during and after the acute attacks. Twenty healthy, age-matched subjects were used as normal control subjects. Nine children with long-term stable asthma were used as control subjects with stable asthma. RESULTS: CD3+, CD4+, CD8+, and IL-2R+ (CD25+) cells; plasma soluble IL-2 receptor; and IgE were significantly higher in patients with acute attacks than in control subjects. (P <.05, P <.05, P <.001, P <.05, P <.0001, and P <.0001, respectively). Immunoelectron microscopy exhibited an increased expression of IL-2R on lymphocytes in acute attacks as compared to control subjects. The abnormalities returned to normal, with the exception of IgE, when clinical remission was achieved after treatment. Correlation analyses revealed a positive relationship between plasma IgE and soluble IL-2R in asthma attacks (r = 0.83, P =.0001). Plasma IgE and soluble IL-2R of those who were in remission positively correlated with their production in acute attacks (r = 0.58, P =.001 and r = 0.71, P =.0001, respectively). CONCLUSION: This study suggests that (1) the percentage of CD4+, CD8+, or IL-2R+ lymphocytes in peripheral blood was significantly elevated during acute attacks and returned to normal ranges after complete remission was achieved; (2) plasma soluble IL-2R is a sensitive marker for asthma activity; and (3) atopic asthmatic children seem to have a hereditary predisposition of having higher levels of soluble IL-2R in asthma attacks, coinherited with the trait of IgE.