Metal trace elements such as cadmium (Cd) are commonly present in ecosystems and could lead to impairment of mitochondrial functions and energy imbalance in aquatic organisms including molluscs. Combined exposure to increasing temperatures and Cd could enhance such an impact on animals. Seasonal fluctuations, such as temperature, and the corresponding reproduction cycle can affect biomarker responses. However, the reproduction cycle stage is rarely taken into account in ecotoxicological studies. Thus, this work aimed at understanding energy metabolism responses in a sentinel species, Dreissena polymorpha. Mussels were collected during the rest and the reproduction periods and were exposed to 10 μg.L-1 of cadmium (Cd) at two temperatures (in situ temperature and in situ temperature + 5°C) during 7 days. Energy metabolism was monitored by measuring reserves and energy nucleotides charge and by assessing aerobic and anaerobic metabolism markers, and upstream regulation pathways. Markers related to OXPHOS activity revealed seasonal variations under laboratory conditions. Conversely, adenylate nucleotides, glycogen, lipid and transcript levels of AMP-activated protein kinase, citrate synthase, ATP synthase and cytochrome b encoding genes remained steady after the acclimation period. No evident effect of Cd on energy metabolism markers was noticed for both exposures although the transcript level of succinate dehydrogenase and citrate synthase encoding genes decreased with Cd during the rest period. Cellular stress, revealed by lipid peroxidation and catalase mRNA levels, only occurred in Cd and warming co-exposed mussels during the reproduction period. These results suggest that contaminant impact might differ according to the reproduction cycle stage. The effect of confounding factors on biomarker variations should be further investigated to have a deeper knowledge of metabolism responses under laboratory conditions.

Pharmacokinetic/pharmacodynamic (PK/PD) analysis using murine infection models is a well-established methodology for optimising antimicrobial therapy. Therefore, we investigated the PK/PD indices of teicoplanin againstStaphylococcus aureus using a murine thigh infection model.

Mice were rendered neutropenic by administration of a two-step dosing of cyclophosphamide. Then, isolates of methicillin-susceptibleS. aureus (MSSA) or methicillin-resistant S. aureus (MRSA) were inoculated into the thighs of neutropenic mice. PK/PD analyses were performed by non-linear least-squared regression using the MULTI program.

Target values offC

/MIC (r

= 0.94) of teicoplanin for static effect and 1 log

kill against MSSA were 4.44 and 15.44, respectively. Target values of fAUC

/MIC (r

= 0.92) of teicoplanin for static effect and 1 log

kill against MSSA were 30.4 and 70.56, respectively. Target values of fC

/MIC (r

= 0.91) of teicoplanin for static effect and 1 log

kill against MRSA were 8.92 and 14.16, respectively. Target values of fAUC

/MIC (r

= 0.92) of teicoplanin for static effect and 1 log

kill against MRSA were 54.8 and 76.4, respectively.

These results suggest thatfC

/MIC and fAUC

/MIC are useful PK/PD indices of teicoplanin against MSSA and MRSA.

These results suggest thatfCmax/MIC and fAUC24/MIC are useful PK/PD indices of teicoplanin against MSSA and MRSA.Carbon-metal composites are promising multifunctional electrocatalysts, but it is still challenging to prepare carbon-metal composites with tunable structure and strong metal-carbon interactions. Here, we present a unique gas-foaming assembly strategy to prepare cytosine-Co chelate derived Co and N codoped carbon nanotube (Co-NCNT). The structure for Co-NCNTs could be easily controlled by regulating cytosine-Co coordination or the carbonization temperature. The optimal Co-NCNT possesses homogeneous distributed NCNTs (10 nm), CoOx (5 nm) and CoNx moieties to synergistically boost electrochemical processes, and offer mesoporous nanosheet architecture to guarantee fast mass migrate and electron transfer. As a result, Co-NCNT shows remarkable ORR performance (onset potential of 0.93 V in 0.1 M KOH electrolyte) along with significant OER and HER activity. More important, it was found that CoNx moieties are responsible for the remarkable electrocatalytic activity in Co-NCNTs, because CoNx could alter active center, enhance metal-carbon synergy, decrease interfacial resistance and reinforce the strength of composites. Therefore, this paper not just demonstrates an advanced multi-functional electrocatalyst, but could also give deep understanding on the designing of multifunctional electrocatalysts.While CDD directly to the CSF can provide a constant delivery of the dopaminergic drug resulting in a more stable treatment effect without the limitations of traditional oral therapy without peripheral effects, it is still young and longitudinal data is lacking. These experimental therapies show promise and further investigation into their efficacy and safety could extend the frontiers for management of PD.

To compare the efficacy and safety between primary GKS and postoperative GKS for acromegaly, and to elucidate predictors associated with endocrine remission, we performed a monocenter, retrospective study.

Seventy-five patients with acromegaly who had received GKS in West China Hospital between March 2010 and December 2018 were included in this study. Endocrine remission was defined as age-sex matched IGF-I normalization and either nadir level of GH <1 ng/mL after OGTT or the random GH < 2.0 ng/mL.

We didn’t find significant differences in endocrine remission, biochemical recurrence, imaging regression, imaging progression, radiation-induced complications between the primary GKS group and the postoperative GKS group(P > 0.05). Actuarial rates of durable endocrine remission at 3, 5, 8 year were 10.60 %, 33.80 % and 70.60 % in the primary GKS group and 6.70 %, 43.40 % and 78.80 % in the postoperative GKS group(P = 0.800). Only base nadir GH after OGTT (HR = 0.637,95 % CI0.416-0.977; P = 0.039) was found to be a predictor of duration endocrine remission.

We find comparable efficacy and safety between primary GKS and postoperative GKS. Lower base nadir GH after OGTT was a positive predictor associated with endocrine remission. GKS should be considered for residual or recurrent tumor after surgery. selleck products For those who couldn’t sustain surgery, GKS is an alternative treatment. Further studies are required to elucidate the efficacy and safety of GKS in acromegaly.

We find comparable efficacy and safety between primary GKS and postoperative GKS. Lower base nadir GH after OGTT was a positive predictor associated with endocrine remission. GKS should be considered for residual or recurrent tumor after surgery. For those who couldn’t sustain surgery, GKS is an alternative treatment. Further studies are required to elucidate the efficacy and safety of GKS in acromegaly.