Efficacy of addition immune checkpoint inhibitors to chemotherapy as first-line treatment for small cell lung cancer patients with liver or brain metastases: a systematic review and meta-analysis.

OBJECTIVE: Differential organ-specific tumor response to immune checkpoint inhibitors (ICIs) has been reported in multiple solid tumors. We aim at investigating the efficacy differences of ICIs combined with chemotherapy (CT) vs. CT alone as first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). MATERIALS AND METHODS: We searched PubMed, Embase, Medline, and China National Knowledge Infrastructure databases to identify relevant trials comparing ICIs combined with CT vs. CT alone in ES-SCLC patients with brain or liver metastases. The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS). The pooled hazard ratio (HR) was analyzed using the fixed or random effects model, according to heterogeneity among included trials. RESULTS: We identified 5 randomized controlled trials of 8 studies that involved a total of 1,401 patients, 310 with brain metastases and 1,091 with liver metastases. The quality of included trials was high. The pooled results showed that ICIs combined with CT significantly improved OS of ES-SCLC with liver metastases (HR 0.88, 95%CI: 0.78-1.00, p=0.049), and a tendency to improve PFS (HR 0.86, 95%CI: 0.68-1.07, p=0.17). For patients with brain metastases, no survival benefit could be obtained from combination therapy of ICIs with CT in terms of PFS (HR 0.91, 95%CI: 0.63-1.32, p=0.62) and OS (HR 1.12, 95%CI: 0.88-1.43, p=0.36). No publication bias was detected. CONCLUSIONS: The addition of ICIs to CT significantly improves OS in ES-SCLC patients with liver metastases compared with CT alone. No survival benefit could be obtained from ICIs and CT combination therapy for ES-SCLC with brain metastases.

[Analysis on identification and traceability of one non-toxigenic Corynebacterium diphtheriae from a patient with diabetic foot in Hainan province].

There is a rare case of an elderly diabetic with diabetic foot infection at Hainan General Hospital in September 2021, which was diagnosed as Corynebacterium diphtheriae infection incidentally on routine culture with conventional methods and molecular biological approaches, to aid in diagnosis in clinical practice. Owing to smear staining, Albert staining and VITEK 2 system, automated identification systems viz matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) confirmed combing with 16S ribosomal RNA (16S rRNA) gene has been used for the taxonomic classification of bacteria. Otherwise, toxin gene tox was done for diphtheria toxin synthesis. The isolate was Gram-stain-positive, rod-like arrangement with irregular thickness, with characteristic metachromatic granules, ferment most sugars and homology of 16S rRNA analyses with C. diphtheriae NCTC11397T (MW682323.1) was greater than a 100% possibility, toxin gene tox was negative. The findings lay the foundation to clinical identify and trace of non-toxigenic C. diphtheriae. Moreover, this work provides insights into the non-toxigenic C.diphtheriae that contribute to recognized risk of non-toxigenic C.diphtheriae infections.

Networked control strategy of dual linear switched reluctance motors based time delay tracking system.

To reduce the influence of time delay on the tracking performance of a direct-drive motion control system, this paper concentrates on stability analysis and cooperative position tracking control issues for the dual linear switched reluctance motors (LSRMs) system with network-induced time delays. The closed-loop network control system (NCS) is constructed by modeling random and bounded network-induced time delays existing in forward and feedback channels as a discrete-time Markov chain. Incremental time delay information is introduced in Lyapunov functional analysis to satisfy the high-precision movement of master and secondary motors and improve the system control performance. The time delay compensation method is proposed to compensate for the damage to the networked control system caused by random delay. With Lyapunov stability theory and LMI are applied, stability and stabilization conditions with less computational complexity and low conservatism are obtained based on incremental time delay information insertion. Finally, the numerical simulation and the experimental platform of the motor control system are built. Simulation and experiment results demonstrate that the networked control strategy can compensate the negative impact of delay on the tracking performance of LSRMs based motion control system.

[Effectiveness of the "14 plus 7 day quarantine" and "nucleic acid plus total antibody testing" strategy for screening imported patients with COVID-19 in Xiamen].

Objective: To analysis effectiveness of the "14 plus 7 day quarantine" and "nucleic acid plus total antibody testing" strategy (combined screening strategy) for screenin the imported patients with COVID-19 in Xiamen. Methods: The study populations were overseas travelers arriving in Xiamen from March 17 to December 31, 2020, and overseas travelers who had quarantine outside Xiamen for less than 21 days from July 18 to December 31, 2020. Data were collected and analyzed on the timing of detection, pathways, and test results of the imported patients with COVID-19 after implementing combined screening strategy. Results: A total of 304 imported patients with COVID-19 were found from 174 628 overseas travelers and 943 overseas travelers from other cities. A total of 163 cases (53.6%) were diagnosed by multitime, multisite intensive nucleic acid testing after positive finding in total antibody testing. Among them, 27 (8.9%) were first positive for nucleic acid in 14 plus 7 day quarantine and 136 were first positive for nucleic acid in 14-day quarantine. Only 8 of these individuals were tested positive for nucleic acid after positive total antibody testing. The other 128 individuals were tested positive for nucleic acid after being negative for average 2.3 times (maximum of 6 times). Aditional 155 cases might be detected by using the combined "14 plus 7 day quarantine" and " nucleic acid plus total antibody testing" strategy compared with "14-day quarantine and nucleic acid testing" strategy, accounting for 51.0% of the total inbound infections. So the combined screening strategy doubled the detection rate for imported patients with COVID-19. No second-generation case caused by overseas travelers had been reported in Xiamen as of February 26, 2021. Conclusions: Xiamen's combined screening strategy can effectively screen the imported patients with COVID-19 who were first positive for nucleic acid after 14 day quarantine. Compared with "14 day quarantine and nucleic acid testing", the combined screening strategy improved detection rate and further reduced the risk of the secondary transmission caused by the imported patients with COVID-19.

Clofazimine for Treatment of Cryptosporidiosis in Human Immunodeficiency Virus Infected Adults: An Experimental Medicine, Randomized, Double-blind, Placebo-controlled Phase 2a Trial.

BACKGROUND: We evaluated the efficacy, pharmacokinetics (PK), and safety of clofazimine (CFZ) in patients living with human immunodeficiency virus (HIV) with cryptosporidiosis. METHODS: We performed a randomized, double-blind, placebo-controlled study. Primary outcomes in part A were reduction in Cryptosporidium shedding, safety, and PK. Primary analysis was according to protocol (ATP). Part B of the study compared CFZ PK in matched individuals living with HIV without cryptosporidiosis. RESULTS: Twenty part A and 10 part B participants completed the study ATP. Almost all part A participants had high viral loads and low CD4 counts, consistent with failure of antiretroviral (ARV) therapy. At study entry, the part A CFZ group had higher Cryptosporidium shedding, total stool weight, and more diarrheal episodes compared with the placebo group. Over the inpatient period, compared with those who received placebo, the CFZ group Cryptosporidium shedding increased by 2.17 log2 Cryptosporidium per gram stool (95% upper confidence limit, 3.82), total stool weight decreased by 45.3 g (P = .37), and number of diarrheal episodes increased by 2.32 (P = .87). The most frequent solicited adverse effects were diarrhea, abdominal pain, and malaise. One placebo and 3 CFZ participants died during the study. Plasma levels of CFZ in participants with cryptosporidiosis were 2-fold lower than in part B controls. CONCLUSIONS: Our findings do not support the efficacy of CFZ for the treatment of cryptosporidiosis in a severely immunocompromised HIV population. However, this trial demonstrates a pathway to assess the therapeutic potential of drugs for cryptosporidiosis treatment. Screening persons living with HIV for diarrhea, and especially Cryptosporidium infection, may identify those failing ARV therapy. CLINICAL TRIALS REGISTRATION: NCT03341767.

Remifentanil protects neurological function of rats with cerebral ischemia-reperfusion injury via NR2B/CaMKIIα signaling pathway.

The effects of remifentanil were studied on cerebral ischemia-reperfusion injury (IRI) in rats, and its regulatory effect was explored on the N-methyl D-aspartate receptor subtype 2B (NR2B)/calcium/calmodulin-dependent protein kinase type II subunit alpha (CaMKII) signaling pathway in cerebral tissues. A total of 40 Sprague-Dawley rats were randomly assigned into sham group, model group, low-dose group (remifentanil injected into the caudal veins at 2 µg/kg) and high-dose group (remifentanil injected into the caudal veins at 10 µg/kg). Then, in the model, low-dose and high-dose groups, the rat model of cerebral IRI was established through middle cerebral artery occlusion (namely, ischemia for 1 h and reperfusion for 2 h), while no thread was inserted into the rats in the sham group. Neurological function of rats in each group was evaluated, and the cerebral infarct size was measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Moreover, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to determine the neuronal apoptosis level, and mitochondrial membrane potential was measured via JC-1 assay. Moreover, the reactive oxygen species (ROS) level in neurons and the malondialdehyde (MDA) content in cerebral tissues were determined using 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay and enzyme-linked immunosorbent assay (ELISA), respectively. Finally, the expression levels of apoptosis-associated proteins and the NR2B/CaMKIIα signaling pathway-associated proteins in cerebral tissues were measured by Western blotting. Remifentanil preconditioning substantially decreased the neurological score of rats (p<0.01), cerebral infarct size (p<0.01), neuronal apoptosis level (p<0.01), ROS level in neurons (p<0.01), MDA content (p<0.01) and expression levels of cysteinyl aspartate specific proteinase-3 (Caspase-3), NR2B, phosphorylated CaMKIIα (p-CaMKIIα) and p-cAMP responsive element binding protein (p-CREB) (p<0.01), but it increased the mitochondrial membrane potential (p<0.01) and B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio (p<0.01). Remifentanil can repress the NR2B/ CaMKIIα signaling pathway in the neurons of rats with cerebral IRI to decrease the p-CREB expression, ROS level and MDA content in neurons, neuronal apoptosis level and cerebral infarct size, and increase the mitochondrial membrane potential, thereby protecting the neurological function.

Aged biochar alters nitrogen pathways in bauxite-processing residue sand: Environmental impact and biogeochemical mechanisms.

Low nitrogen (N) content and retention in bauxite-processing residue sand (BRS) disposal areas pose a great challenge to the establishment of sustainable vegetation cover in this highly alkaline environment. The budget and fate of applied N in BRS and its potential environmental impacts are largely unknown. We investigated the effect of combined application of biochars [aged acidic (AC) vs alkaline pine (PC)] and di-ammonium phosphate (DAP) fertiliser on ammonia (NH3) volatilisation, nitrous oxide (N2O) emission and N retention in a 116-day glasshouse study. The application of AC to BRS decreased pH (≈0.5 units) in BRS, while PC biochar increased pH (≈0.3 units). The application of AC reduced NH3 volatilisation by ca. 80%, while PC by ca. 25%. On the other hand, the AC treatment increased N2O emission by 5 folds. However, the N loss via N2O emission in the AC treatment only accounted for ca. 0.4% of applied N. The reduction in BRS pH and increased retention of mineral N due to the presence of oxygen-containing (phenolic and carboxylic) functional groups in AC may be responsible for reduced NH3 volatilisation and increased N2O emission. This study has highlighted the potential of biochar (particularly aged biochar) in improving N retention and minimising environmental impacts in highly alkaline environments.

[Comparison of effects of two anesthesia methods on the first night sleep quality in middle-aged and elderly patients undergoing surgery for lower extremity varicose vein].

Objective: To investigate effects of two anesthesia methods on the first night sleep quality in middle-aged and elderly patients after surgery. Methods: This was a prospective study conducted from November 2017 to March 2018. Sixty patients, aged 50-70, undergoing elective surgery for unilateral lower extremity varicose vein at Ningbo No.2 Hospital, with American Society of Anesthesiologists (ASA) grade Ⅰ or Ⅱ, were enrolled and randomly allocated to two groups (n=30), general anesthesia group and spinal anesthesia group. On the first day before surgery, the patient's general data were collected and the Pittsburgh sleep quality index (PSQI) was used to assess the patient's sleep status in the past month. The postoperative mean arterial pressure (MAP), heart rate (HR) and pulse oxygen saturation (SpO(2)) in the ward were recorded with a multi-function monitor on first night after surgery. The total sleep time and arousal time were obtained by bispectral index (BIS) monitoring from 20: 00 (the first day) to 6: 00 (the second day). Athens Insomnia Scale (AIS) was recorded at 18: 00 at the second day after surgery. Results: There was no significant difference in general data and PSQI scale scores between the two groups of patients (all P>0.05). And there were no significant differences in MAP, HR, SpO(2) and BIS every 2 hours between the two groups from 20: 00 (the first day) to 6: 00 (the second day)(all P>0.05). Compared with the general anesthesia group, the first night of total sleep time in the spinal anesthesia group was significantly shorter[(357.2±83.4)min vs (275.1±64.8)min, t=-9.635, P<0.05], while the rate of wakefulness, total sleep time, overall sleep quality, daytime mood and daytime physical function were significantly higher[(25.9%, 22.2%, 25.9%, 18.5%18.5%) vs (51.7%, 51.7%, 55.2%, 48.3%44.8%), χ(2)=3.901, 5.192, 4.941, 5.523 and 4.437, all P<0.05], and the cases of postoperative urinary retention and lower limb discomfort were significantly higher[(8 and 6) vs (1 and 0), all P<0.05]. Conclusion: Both anesthesia methods can be safely and effectively applied to middle-aged and elderly patients with lower extremity varicose veins surgery, but patients with general anesthesia show fewer adverse reactions on the first night after surgery and have better sleep quality.

Assessment of N2O emissions from a fertilised vegetable cropping soil under different plant residue management strategies using 15N tracing techniques.

Combined application of plant residues and N fertilisers strongly affect soil mineral N dynamics and N2O emissions depending on the quality of the plant residues, their application methods and other management strategies. We investigated the effect of combined application of two vegetable plant residues (cauliflower and sweet corn) and 15N fertiliser on N dynamics and N2O emission in a glasshouse pot study. The experiment was conducted under two residue management practices (soil incorporation vs surface mulching) over 98days with growing basil (Ocimum basilicum) plants. We also assessed the efficacy of applying the nitrification inhibitor, 3,4-dimethylpyrazole phosphate (DMPP) to the plant residues, for reducing N loss and mitigating N2O emissions. Application of plant residues, both on the soil surface or into soil, resulted in net N mineralisation and increased cumulative N2O emission compared with the application of N fertiliser alone. Soil surface mulching of sweet corn decreased total and residue-induced cumulative N2O emission compared with the incorporation method, while it showed opposite effect on N2O emissions from cauliflower residue. The application of DMPP with sweet corn residue reduced total, residue- and fertiliser-induced N2O emissions; however its application with cauliflower residue did not show any mitigating effect on the N2O emissions. The residue application methods and the use of DMPP did not significantly affect 15N recovery by the basil plants. In contrast, soil incorporation of these residues doubled the microbial immobilisation of applied 15N into soil organic matter. Linear regression analysis of N2O emission during the experimental period indicated that in the treatments without DMPP application, soil NO3--N concentration was the most important factor in controlling the magnitude of N2O emissions, while the application of DMPP changed the dominant regulating factor from NO3--N to NH4+-N concentration.

Temporal Changes Rather than Long-Term Repeated Burning Predominately Control the Shift in the Abundance of Soil Denitrifying Community in an Australian Sclerophyll Forest.

To understand the temporal dynamics of soil bacterial denitrifying community in response to long-term prescribed burning and its resilience and recovery following a fire, a wet sclerophyll forest study site under two treatments (2 yearly burning (2YB) and no burning (NB)) and with 40-year-old burning history was used. Similar temporal patterns in the abundance of total (16S rRNA) and denitrifying (narG, nirK, nirS, nosZ) bacteria between two burning treatments revealed strong temporal influences. The magnitude of burning impacts on the abundance of 16S rRNA and denitrification genes was smaller compared with the impact of sampling time, but significant burning and temporal impacts were recorded for all (P < 0.001)-except for the nirS gene. Impacts of prescribed fire on the abundance of soil denitrifying community could be observed immediately after fire, and this impact diminished over a 24-month period prior to the next prescribed burning event. In conclusion, temporal changes govern the fluctuations of the abundance of soil denitrifying genes over the sampling period and the denitrifying community can recover after fire, suggesting that this community is resilient to the effects of prescribed burning. A combination of biotic and abiotic factors may account for the different temporal dynamics of denitrification gene abundance.

Stoichiometric ratio of dissolved organic carbon to nitrate regulates nitrous oxide emission from the biochar-amended soils.

Biochar has the potential to mitigate nitrous oxide (N2O) emissions from soils. However, the mechanisms responsible for N2O emission in biochar-amended soils are yet to be elucidated. In this study, an incubation experiment was carried out to investigate the effects of seven biochars (eucalyptus, softwood mixture, mallee, jarrah, peanut shell, green waste and radiata pine) on the stoichiometric shifts of dissolved organic carbon (DOC), nitrate (NO3--N) and N2O emission in two contrasting soils (Ferrosol with 5.3% total C, 0.46% total N; Tenosol with 0.4% total C, 0.01% total N). All biochar treatments were found to significantly reduce N2O emission in Tenosol by 61-72%. However, in Ferrosol, biochars' impacts on N2O emission were variable, with only peanut shell, green waste and radiata pine bicohars significantly reducing N2O emission by 17-23%. A decrease in NO3- availability in most biochar-amended treatments also was observed in both soils compared with the control. The N2O fluxes in Ferrosol were mainly regulated by the shifts in the availability and stoichiometry of DOC and NO3- induced by the biochar amendments. The DOC derived from biochars increased DOC:NO3- ratio in Ferrosol at the beginning of the experiment, but these effects disappeared 7days after incubation. Overall, the N2O fluxes were C-limited due to the presence of high concentrations of NO3- in Ferrosol. However, in Tenosol, the relationship between stoichiometry of DOC:NO3- and N2O fluxes was much weaker than Ferrosol and N2O fluxes mainly limited by the concentration of NO3-. This study demonstrated that the mechanisms responsible for biochar effects on soil N2O fluxes are considered to be soil and biochar specific.

Long term repeated fire disturbance alters soil bacterial diversity but not the abundance in an Australian wet sclerophyll forest.

Effects of fire on biogeochemical cycling in terrestrial ecosystem are widely acknowledged, while few studies have focused on the bacterial community under the disturbance of long-term frequent prescribed fire. In this study, three treatments (burning every two years (B2), burning every four years (B4) and no burning (B0)) were applied for 38 years in an Australian wet sclerophyll forest. Results showed that bacterial alpha diversity (i.e. bacterial OTU) in the top soil (0-10 cm) was significantly higher in the B2 treatment compared with the B0 and B4 treatments. Non-metric multidimensional analysis (NMDS) of bacterial community showed clear separation of the soil bacterial community structure among different fire frequency regimes and between the depths. Different frequency fire did not have a substantial effect on bacterial composition at phylum level or bacterial 16S rRNA gene abundance. Soil pH and C:N ratio were the major drivers for bacterial community structure in the most frequent fire treatment (B2), while other factors (EC, DOC, DON, MBC, NH4(+), TC and TN) were significant in the less frequent burning and no burning treatments (B4 and B0). This study suggested that burning had a dramatic impact on bacterial diversity but not abundance with more frequent fire.

Ten-year follow-up of hepatitis B relapse after cessation of lamivudine or telbivudine treatment in chronic hepatitis B patients.

The high rate of relapse after cessation of nucleos(t)ide analogues (NUCs) treatment in chronic hepatitis B (CHB) patients leads us to reassess the feasibility for off-therapy, but long-term follow-up data are scarce. We assessed the feasibility for off-therapy by a long-term observation of relapse in response to lamivudine (LAM) and telbivudine (LdT). Eighty-six NUC-naive CHB patients, treated with LAM (n = 46) or LdT (n = 40) who reached the guidelines recommended for off-therapy, were followed for up to 10 years. Hepatitis B virus (HBV), viral serology and biochemistries were periodically determined. COX model was used to predict the risk of relapse. A total of 52.3% of patients experienced relapse within a median of 115 months (range, 61-122 months). A total of 93.3% of relapses occurred within 48 months. Relapse rates in hepatitis B e antigen (HBeAg)-positive (n = 56) and HBeAg-negative (n = 30) patients were 39.3% and 76.7%, respectively (p < 0.01). HBeAg-positive patients who achieved an early viral response (EVR), defined as undetectable HBV DNA within 6 months, had a lower relapse rate compared to non-EVR patients (21.4% vs. 59.2%, p < 0.01). EVR patients who had both lower HBV DNA (<10(6) copies/mL) at baseline and lower hepatitis B surface antigen (HBsAg) at end of treatment had a relapse rate of 10.7%. The high relapse rates in CHB patients over this 10-year follow-up make LAM or LdT off therapy infeasible in most of the cases, except in the case of HBsAg loss and/or seroconversion. HBeAg-positive patients with EVR, lower HBV DNA and HBsAg had lower relapse rates and could be good candidates for off-therapy. Long-term monitoring, especially during the first 4 years, is critical for patients off-therapy.

Development of thermal energy storage materials for biomedical applications.

The phase change materials (PCMs) have been utilized widely for solar thermal energy storage (TES) devices. The quality of these materials to remain at a particular temperature during solid-liquid, liquid-solid phase transition can also be utilized for many biomedical applications as well and has been explored in recent past already. This study reports some novel PCMs developed by them, along with some existing PCMs, to be used for such biomedical applications. Interestingly, it was observed that the heating/cooling properties of these PCMs enhance the quality of a variety of biomedical applications with many advantages (non-electric, no risk of electric shock, easy to handle, easy to recharge thermally, long life, cheap and easily available, reusable) over existing applications. Results of the present study are quite interesting and exciting, opening a plethora of opportunities for more work on the subject, which require overlapping expertise of material scientists, biochemists and medical experts for broader social benefits.

Hindering factors and suggestions related to organ donation decisions: perspective of the Taiwan Ali-Shan Tsou aboriginal tribe.

BACKGROUNDS AND AIMS: Ali-San Tsou (AST) is one of leading aboriginal tribes in Taiwan with traditional godly beliefs related to life and death. Lacking related knowledge, health professionals (HPs) often failed to help them reach good dying or organ donation (OD). This study aimed to explore hindering factors and suggestions related to OD for good dying from Taiwan AST's own perspective. METHODS: An explorative qualitative design was employed using a purposive sample of the AST tribes from Taiwan. Data were collected with AST residents by face-to-face interviews and analyzed by content analysis. RESULTS: Thirty AST residents (16 females and 14 males) with ages ranging from 28 to 78 (mean, 54.5) years completed interviews. Of them, 85% reported various diseases. In this study 73% were Catholics and Christians, 17% held traditional godly believes, and 10% had no religious affiliation. Eight hindering factors were reported: (1) limited information about organs and OD; (2) no qualified organs for donation; (3) worry about lack of forgiveness by ancestors; (4) tribe elders who might not accept concept of OD; (5) intact bodies were required at home during spirit-companion rituals; (6) earth burial with intact bodies was preferred; (7) bodies due to accidental and bad death were impermissible for OD; and (8) worry about possession by the donor's spirit. Seven suggestions were also reported for HPs to enhance AST's OD decisions: (1) starting with friendship and a caring relationship; (2) providing spiritual support from reverent religions; (3) stressing good deeds and honoring tribe folks by OD; (4) avoiding accidental/bad death; (5) providing relevant modern medical knowledge of human organs and OD; (6) introducing OD as part of a good-dying care plan; and (7) demonstrating a respectful discussion mindset about OD. CONCLUSIONS: Eight hindering factors and 7 types of suggestions for enhancing AST aboriginal people's OD decisions were first explored in this project. In the future, HPs are encouraged to invite AST to share the concepts of OT and try to clarify the related concerns with respect for their cultural contexts. With mutual respect, the efforts of sharing and integrating OD into good-dying care would be more possible.

Molecular composition of recycled organic wastes, as determined by solid-state 13C NMR and elemental analyses.

Using solid state (13)C NMR data and elemental composition in a molecular mixing model, we estimated the molecular components of the organic matter in 16 recycled organic (RO) wastes representative of the major materials generated in the Sydney basin area. Close correspondence was found between the measured NMR signal intensities and those predicted by the model for all RO wastes except for poultry manure char. Molecular nature of the organic matter differed widely between the RO wastes. As a proportion of organic C, carbohydrate C ranged from 0.07 to 0.63, protein C from <0.01 to 0.66, lignin C from <0.01 to 0.31, aliphatic C from 0.09 to 0.73, carbonyl C from 0.02 to 0.23, and char C from 0 to 0.45. This method is considered preferable to techniques involving imprecise extraction methods for RO wastes. Molecular composition data has great potential as a predictor of RO waste soil carbon and nutrient outcomes.

c-Met is a prognostic marker and potential therapeutic target in clear cell renal cell carcinoma.

BACKGROUND: Activation of the c-Met pathway occurs in a range of malignancies, including papillary renal cell carcinoma (RCC). Its activity in clear cell RCC is less clear. We investigated c-Met expression and inhibition in a large cohort of RCC tumors and cell lines. METHODS: c-Met protein expression was determined by automated quantitative analysis (AQUA) on a tissue microarray (TMA) constructed from 330 RCC tumors paired with adjacent normal renal tissue. c-Met expression and selective inhibition with SU11274 and ARQ 197 were studied in clear cell RCC cell lines. RESULTS: Higher c-Met expression was detected in all RCC subtypes than in the adjacent normal renal tissue (P < 0.0001). Expression was highest in papillary and sarcomatoid subtypes, and high-grade and stage tumors. Higher c-Met expression correlated with worse disease-specific survival [risk ratio = 1.36; 95% confidence interval (CI) 1.08-1.74; P = 0.0091] and was an independent predictor of survival, maintained in clear cell subset analyses. c-Met protein was activated in all cell lines, and proliferation (and colony formation) was blocked by SU11274 and ARQ 197. CONCLUSIONS: c-Met is associated with poor pathologic features and prognosis in RCC. c-Met inhibition demonstrates in vitro activity against clear cell RCC. Further study of ARQ 197 with appropriate biomarker studies in RCC is warranted.

Difficulties in organ procurement and transplantation in the aboriginal minority people in Taiwan.

BACKGROUND: Aboriginal people (AP) are a minority group in Taiwan. Little information on their perspectives on organ transplantation (OT) is available. Their rights for organ donation (OD) and as OT recipients (OTR) are constrained as a vulnerable population in society. This research sought to explore various Highland Aborigine Tribes beliefs systems and concepts related to OT. METHODS: We employed a qualitative design on a purposive sample including seven categories of Taiwanese AP. Data collected by face-to-face interviews were evaluated by content analysis. RESULTS: Seventy-five informants (45 female and 30 males) of 18 to 82 years from seven tribes completed interviews: Bunun (n = 20), Shao (n = 18), Tsou (n = 15), Amis (n = 12), Truku (n = 4), Rukai (n = 3), and Puyuma (n = 3). Of there, 33% had no idea of OT. All informants reported lack of knowledge of OD, organ procurement, and OTR. Eighty percent (45-82 years) had no willingness for OD or OTR; others might consult family members and health professionals (HP) to learn about OT. Seven hindering factors were identified: (1) having no background of OT; (2) limited impressions obtained from television news reports; (3) negative concepts of donating one's organs to others; (4) OT concepts contrast with cultural meanings of death; (5) possibility of being stigmatized; (6) fear of being rejected by others; and (7) HP had never mentioned OT. CONCLUSIONS: Taiwan APs' perspectives of OT concepts showed the majority to be unfamiliar with the concept and benefits of OT. Future research is necessary to explore the possible avenues to facilitate communications between HP and AP leaders, as well as elders in each AP category in Taiwan.

Expression and significance of lipin1 and AMPKα in hepatic insulin resistance in diet-induced insulin resistance rats.

BACKGROUND: Lipin1, a lately indentified adipokine, may link obesity with insulin resistance and diabetes. The present study aimed to investigate the changes and significance of lipin1 expression and lipin1-AMPK signaling in diet-induced hepatic insulin resistance. METHODS: 24 4-week-old Male Wistar rats were randomly divided into 2 groups: (1) control group (CO), (2) high-fat diet group (HF). Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp technique. The mRNA levels of α1 and α2 subunit of AMPKα as well as Lipin1 were measured using Real-time RT-PCR. The activities of AMPKα and Akt were evaluated by detection of p-AMPKα (Thr-172) and p-Akt (ser473) by Western blot. RESULTS: After treatment of 4 months, HF group showed significantly increased levels of body weight, fasting plasma glucose and insulin levels; Plasma and liver total cholesterol (TC), triglycerides (TG) levels were also markedly elevated; Lipin1 expression at both mRNA and protein levels were significantly deceased. Compared with CO group, the mRNA and protein levels of AMPKα1 and AMPKα2 were not changed, whereas the p-AMPK (Thr-172) and p-AKT (ser473) levels in liver were significantly decreased in HF group. CONCLUSIONS: These findings indicated that the decrease in lipin1 expression and AMPKα activation may contribute to hepatic insulin resistance in diet-induced obese rats.

Deletion of thyrotropin receptor residue Asp403 in a hyperfunctioning thyroid nodule provides insight into the role of the ectodomain in ligand-induced receptor activation.

Somatic mutations of the TSH receptor (TSHR) gene are the main cause of autonomously functioning thyroid nodules. Except for mutations in ectodomain residue S281, all of the numerous reported activating mutations are in the TSHR membrane-spanning region. Here, we describe a patient with a toxic adenoma with a novel heterozygous somatic mutation caused by deletion of ectodomain residue Asp403 (Del-D403). Subsequent in vitro functional studies of the Del-D403 TSHR mutation demonstrated greatly increased ligand-independent constitutive activity, 8-fold above that of the wild-type TSHR. TSH stimulation had little further effect, indicating that the mutation produced near maximal activation of the receptor. In summary, we report only the second TSHR ectodomain activating mutation (and the first ectodomain deletion mutation) responsible for development of a thyroid toxic adenoma. Because Del-D403 causes near maximal activation, our finding provides novel insight into TSHR structure and function; residue D403 is more likely to be involved in the ligand-mediated activating pathway than in the ectodomain inverse agonist property.