A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi （n = 10） and primary malignant melanomas （n = 10）, using quantitative real-...A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi （n = 10） and primary malignant melanomas （n = 10）, using quantitative real-time PCR. Differential expression was found for 72 microRNAs. Members of the let-7 family of microRNAs were significantly downregulated in primary melanomas as compared with benign nevi, suggestive for a possible role of these molecules as tumor suppressors in malignant melanoma. Interestingly, similar findings had been described for lung and colon cancer. Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1, D3, and A, and cyclin-dependent kinase （Cdk） 4, all of which had been described to play a role in melanoma development. The effect oflet-7b on protein expression was due to targeting of 3＇-untranslated regions （3＇UTRs） of individual mRNAs, as exemplified by reporter gene analyses for cyclin D1. In line with its downmodulating effects on cell cycle regulators, let-7b inhibited cell cycle progression and anchorage-independent growth of melanoma cells. Taken together, these findings not only point to new regulatory mechanisms of early melanoma development, but also may open avenues for future targeted therapies of this tumor.展开更多
This study compared the efficacy of 70- and 120-w 2-μm thulium：YAG VapoEnucleation of the prostate （ThuVEP） for patients with benign prostatic obstruction （BPO）. A prospective analysis of 84 patients with sympto...This study compared the efficacy of 70- and 120-w 2-μm thulium：YAG VapoEnucleation of the prostate （ThuVEP） for patients with benign prostatic obstruction （BPO）. A prospective analysis of 84 patients with symptomatic BPO and prostatic enlargement （t〉 60 ml） who underwent either 70-w （n=44） or 120-w ThuVEP （n=40） non-randomly was carried out. Patient demographics and perioperative and 12-month follow-up data were analysed. The mean prostate volume was 79.90---27.49 ml in patients who had received 70-w ThuVEP, which was less than in those who had received 120-w ThuVEP （88.53＋-25.10; P=0.033）. The mean enucleation （resected weight/laser time, 2.16±1.21 g min-1 vs. 1.23±0.60 g min-1; P=-0.013）, operation efficiency （resected weight/total operation time, 0.76±0.35 g min-1 vs. 0.42＋-0.27 g min-1; P=-0.000） and percentage of resected tissue （66.93%±22.79% vs. 45.41%±23.33%; P=-0.000） were higher with 120-w treatment compared to 70-w ThuVEP. One patient （1.2% of total patients） （in the 120-w group） required a blood transfusion postoperatively. Sixty-one patients （73%） were available for review at the 12-month follow-up time point. The quality of life （QoL）, International Prostate Symptom Score （IPSS）, maximum urinary flow rate （Qmax）, postvoiding residual urine （PVR） and prostate volume improved significantly after treatment （P≤ 0.035） and were not significantly different between those treated with the different devices （70- and 120-w）. The median prostate volume reduction was 81.70% and 82.19% with 70- and 120-w ThuVEP, respectively. The incidence of complications was low and did not differ between groups treated with the different devices. Two patients （2.4%） （one per group） had a bladder neck contracture at the follow-up. ThuVEP is a safe and efficacious procedure for the treatment of symptomatic BPO. The incidence of complications was low with both devices. The 120-w thulium：YAG device enhances the effectiveness of Th,VE展开更多
AIM:To describe disease characteristics and treatment modalities in a group of rare patients with metastatic gastric carcinoid type 1(GCA1).METHODS:Information on clinical,biochemical,radiological,histopathological fi...AIM:To describe disease characteristics and treatment modalities in a group of rare patients with metastatic gastric carcinoid type 1(GCA1).METHODS:Information on clinical,biochemical,radiological,histopathological findings,the extent of the disease,as well as the use of different therapeutic modalities and the long-term outcome were recorded.Patients’data were assessed at presentation,and thereafter at 6 to 12 monthly intervals both clinically and biochemically,but also endoscopically and histopathologically.Patients were evaluated for the presence of specific symptoms;the presence of autoimmune disorders and the presence of other gastrointestinal malignancies in other family members were also recorded.The evaluation of response to treatment was defined using established WHO criteria.RESULTS:We studied twenty consecutive patients with a mean age of 55.1 years.The mean follow-up period was 83 mo.Twelve patients had regional lymph node metastases and 8 patients had liver metastases.The primary tumor mean diameter was 20.13±10.83mm(mean±SD).The mean Ki-67 index was 6.8%±11.2%.All but one patient underwent endoscopic or surgical excision of the tumor.The disease was stable in all but 3 patients who had progressive liver disease.All patients remained alive during the follow-up period.CONCLUSION:Metastatic GCA1 carries a good overall prognosis,being related to a tumor size of≥1 cm,an elevated Ki-67 index and high serum gastrin levels.展开更多
Over the past two decades considerable progress has been made in understanding the ototoxic effects and mechanisms underlying loop diuretics. As typical representative of loop diuretics ethacrynic acid or furosemide o...Over the past two decades considerable progress has been made in understanding the ototoxic effects and mechanisms underlying loop diuretics. As typical representative of loop diuretics ethacrynic acid or furosemide only induces temporary hearing loss, but rarely permanent deafness unless applied in severe acute or chronic renal failure or with other ototoxic drugs. Loop diuretic induce unique pathological changes in the cochlea such as formation of edematous spaces in the epithelium of the stria vascularis, which leads to rapid decrease of the endolymphatic potential and eventual loss of the cochlear microphonic potential, summating potential, and compound action potential. Loop diuretics interfere with strial adenylate cyclase and Nat/Kt-ATPase and inhibit the Na-K-2Cl cotransporter in the stria vascularis, however recent reports indicate that one of the earliest effects in vivo is to abolish blood flow in the vessels supplying the lateral wall. Since ethacrynic acid does not damage the stria vascularis in vitro, the changes in Nat/Kt-ATPase and Na-K-2Cl seen in vivo may be secondary effects results from strial ischemia and anoxia. Recent observations showing that renin is present in pericytes surrounding stria arterioles suggest that diuretics may induce local vasoconstriction by renin secretion and angiotensin formation. The tight junctions in the blood-cochlea barrier prevent toxic molecules and pathogens from entering cochlea, but when diuretics induce a transient ischemia, the barrier is temporarily disrupted allowing the entry of toxic chemicals or pathogens.展开更多
Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to estradiol ratio.In this subset of patients,and particula...Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to estradiol ratio.In this subset of patients,and particularly in those with hypogonadism,elevated levels of circulating estradiol may establish a negative feedback on the hypothalamic–pituitary–testicular axis by suppressing follicle-stimulating hormone(FSH)and luteinizing hormone(LH)production and impaired spermatogenesis.Hormonal manipulation via different agents such as selective estrogen modulators or aromatase inhibitors to increase endogenous testosterone production and improve spermatogenesis in the setting of infertility is an off-label option for treatment.We carried out a systematic review and meta-analysis of the literature of the past 30 years in order to evaluate the benefits of the use of aromatase inhibitors in the medical management of infertile/hypoandrogenic males.Overall,eight original articles were included and critically evaluated.Either steroidal(Testolactone)or nonsteroidal(Anastrozole and Letrozole)aromatase inhibitors were found to statistically improve all the evaluated hormonal and seminal outcomes with a safe tolerability profile.While the evidence is promising,future prospective randomized placebo-controlled multicenter trials are necessary to better define the efficacy of these medications.展开更多
BACKGROUND Prophylactic antibiotics have significantly led to a reduction in the risk of postoperative surgical site infections(SSI)in orthopaedic surgery.The aim of using antibiotics for this purpose is to achieve se...BACKGROUND Prophylactic antibiotics have significantly led to a reduction in the risk of postoperative surgical site infections(SSI)in orthopaedic surgery.The aim of using antibiotics for this purpose is to achieve serum and tissue drug levels that exceed,for the duration of the operation,the minimum inhibitory concentration of the likely organisms that are encountered.Prophylactic antibiotics reduce the rate of SSIs in lower limb arthroplasty from between 4%and 8%to between 1%and 3%.Controversy,however,still surrounds the optimal frequency and dosing of antibiotic administration.AIM To evaluate the impact of introduction of a weight-adjusted antibiotic prophylaxis regime,combined with a reduction in the duration of administration of post-operative antibiotics on SSI incidence during the 2 years following primary elective total hip and knee arthroplasty METHODS Following ethical approval,patients undergoing primary total hip arthroplasty(THA)/total knee arthroplasty(TKA)with the old regime(OR)of a preoperative dose[cefazolin 2 g intravenously(IV)],and two subsequent doses(2 h and 8 h),were compared to those after a change to a new regime(NR)of a weight-adjusted preoperative dose(cefazolin 2 g IV for patients<120 kg;cefazolin 3g IV for patients>120 kg)and a post-operative dose at 2 h.The primary outcome in both groups was SSI rates during the 2 years post-operatively.RESULTS A total of n=1273 operations(THA n=534,TKA n=739)were performed in n=1264 patients.There was no statistically significant difference in the rate of deep(OR 0.74%(5/675)vs NR 0.50%(3/598);fishers exact test P=0.72),nor superficial SSIs(OR 2.07%(14/675)vs NR 1.50%(9/598);chi-squared test P=0.44)at 2 years postoperatively.With propensity score weighting and an interrupted time series analysis,there was also no difference in SSI rates between both groups[RR 0.88(95%CI 0.61 to 1.30)P=0.46].CONCLUSION A weight-adjusted regime,with a reduction in number of post-operative doses had no adverse impact on SSI incidence in this population.展开更多
The homeoprotein encoded by the intestinal-specific Cdx2 gene is a major regulator of gut development and homeostasis,also involved in colon cancer as well as in intestinal-type metaplasias when it is abnormally expre...The homeoprotein encoded by the intestinal-specific Cdx2 gene is a major regulator of gut development and homeostasis,also involved in colon cancer as well as in intestinal-type metaplasias when it is abnormally expressed outside the gut.At the molecular level,structure/function studies have demonstrated that the Cdx2 protein is a transcription factor containing a conserved homeotic DNA-binding domain made ofthree alpha helixes arranged in a helix-turn-helix motif,preceded by a transcriptional domain and followed by a regulatory domain.The protein interacts with several thousand sites on the chromatin and widely regulates intestinal functions in stem/progenitor cells as well as in mature differentiated cells.Yet,this transcription factor also acts trough original nontranscriptional mechanisms.Indeed,the identification of novel protein partners of Cdx2 and also of a splicing variant revealed unexpected functions in the control of signaling pathways like the Wnt and NF-k B pathways,in double-strand break DNA repair and in premessenger RNA splicing.These novel functions of Cdx2 must be considered to fully understand the complexity of the role of Cdx2 in the healthy intestine and in diseases.展开更多
Pet owner compliance is essential for the success of veterinary healthcare strategies. As some parasites are zoonotic, consistent parasite control is an integral part of the One-Health strategy. Highly palatable formu...Pet owner compliance is essential for the success of veterinary healthcare strategies. As some parasites are zoonotic, consistent parasite control is an integral part of the One-Health strategy. Highly palatable formulations help ensure compliance, as they offer a positive experience for the dog and the owner. This study was conducted to ascertain if dogs exhibited a preference between two commercially available oral formulations of broad-spectrum endectoparasiticides, NexGard Spectra (afoxolaner and milbemycin oxime) and Simparica Trio (sarolaner, moxidectin and pyrantel). For four consecutive days, 100 healthy dogs were offered both products and consumption was recorded. If one product was more consumed than the other, it was defined as the preferred product. No adverse event was recorded throughout the study. A total of 358 chewable tablets were consumed over four study days;78.5% of dogs voluntarily consumed NexGard Spectra (281 chews), while 21.5% of dogs voluntarily consumed Simparica Trio (77 chews, <i>p</i> < 0.01). Among 75 dogs which demonstrated a preference for a product, significantly more dogs preferred NexGard Spectra (94.7%) compared to Simparica Trio (5.3%) (<i>p</i> < 2.2 × 10<sup>-16</sup>), resulting in a preference ratio of 17.75 to 1 for NexGard Spectra.展开更多
Objective To study the sensitivity and specificity of different staining methods to monitor apoptosis induced by oxidative stress in adherent cells.Methods Sensitivity and specificity of several common methods for apo...Objective To study the sensitivity and specificity of different staining methods to monitor apoptosis induced by oxidative stress in adherent cells.Methods Sensitivity and specificity of several common methods for apoptosis determination were evaluated (Apo2.7-expression, Annexin V-binding, TUNEL-reaction, poly-(ADP-ribose)-polymerase-(PARP) cleavage and single-stranded-DNA (ssDNA) staining). Apoptosis was induced by oxidative stress generated by hydrogen peroxide in 3 cultured cells types growing as adherent monolayer (MiaPaCa-2, Hep-G2 and human skin fibroblasts), necrosis was induced by depletion of cellular ATP using sodium azide. Cells positively stained by the respective apoptosis assay were quantified and alterations of cell morphology were monitored by fluorescence microscopy. The date was analyzed by one-way analysis of variance and significance test of correlation coefficient.Results One hour after apoptosis induction significant cell fractions were positively stained for ssDNA (33% with MiaPaCa-2 cells, 35% with Hep-G2 cells, 56% with human skin fibroblasts). PARP-cleavage was less sensitive compared to the ssDNA-staining. Apo2.7-expression, Annexin V-binding and TUNEL-reaction were not applicable to detect early apoptosis induced by oxidative stress (below 2 hours), but were efficiently monitoring late apoptosis. Specificity of ssDNA-staining was complete with each cell type even 4 hs after induction of necrosis by the highest sodium azide concentration. In contrast, the same experimental conditions resulted in 50%-90% positively stained necrotic cells by using Apo2.7-expression, TUNEL-reaction or AnnexinV-binding. Surprisingly, specificity of PARP-cleavage was highly depending on the respective cell type.Conclusions Our study prove that among the five methods investigated only ssDNA-staining allowed to completely differentiate apoptosis from necrosis, and is thus suitable to reliably detect early as well as late apoptosis. Therefore, the ssDNA-staining may be used as reference method to clearly ide展开更多
Fresh straw burning （SB） particles were generated in the laboratory by the combustion of rice straw and corn straw. The chemical composition and mixing state of the fresh SB particles were investigated by an Aerosol...Fresh straw burning （SB） particles were generated in the laboratory by the combustion of rice straw and corn straw. The chemical composition and mixing state of the fresh SB particles were investigated by an Aerosol Time-of-Flight Mass Spectrometer （ATOFMS）. Based on the mass spectral patterns, the SB particles were clustered into four major types： Salt, Organic Carbon （OC）, Elemental Carbon （EC）, and internally mixed particles of EC and OC （EC-OC）. In addition, particles containing ash, polycyclic aromatic hydrocarbons, heavy metals or nicotine were also observed. Physical and chemical changes of the SB particles immediately after the emission were analyzed with highly time-resolved data. During the aging processes, the average particle size increased steadily. Freshly emitted organic compounds were gradu- ally oxidized to more oxygenated compounds in the OC- containing particles. Meanwhile, an important displace- ment reaction （2KCI＋ SO24- KzSO4 ＋ 2C1-） was observed. The marker ions for SB particles were optimized and applied to identify the SB particles in the ambient atmosphere. The fluctuation of the number fraction of ambient SB particles sorted by ATOFMS agrees well with that of water soluble K＋ measured by an online ion chromatography, demonstrating that the optimized marker ions could be good tracers for SB particles in field measurements.展开更多
Microscopy with extreme ultraviolet(EUV)radiation holds promise for high-resolution imaging with excellent material contrast,due to the short wavelength and numerous element-specific absorption edges available in this...Microscopy with extreme ultraviolet(EUV)radiation holds promise for high-resolution imaging with excellent material contrast,due to the short wavelength and numerous element-specific absorption edges available in this spectral range.At the same time,EUV radiation has significantly larger penetration depths than electrons.It thus enables a nano-scale view into complex three-dimensional structures that are important for material science,semiconductor metrology,and next-generation nano-devices.Here,we present high-resolution and material-specific microscopy at 13.5 nm wavelength.We combine a highly stable,high photon-flux,table-top EUV source with an interferometrically stabilized ptychography setup.By utilizing structured EUV illumination,we overcome the limitations of conventional EUV focusing optics and demonstrate high-resolution microscopy at a half-pitch lateral resolution of 16 nm.Moreover,we propose mixed-state orthogonal probe relaxation ptychography,enabling robust phase-contrast imaging over wide fields of view and long acquisition times.In this way,the complex transmission of an integrated circuit is precisely reconstructed,allowing for the classification of the material composition of mesoscopic semiconductor systems.展开更多
Interfacial solar desalination is an emerging technology for freshwater production,but the finding of novel solar evaporators is still challenging.In the present research,graphitic carbon foam(CF)was synthesized from ...Interfacial solar desalination is an emerging technology for freshwater production,but the finding of novel solar evaporators is still challenging.In the present research,graphitic carbon foam(CF)was synthesized from the upcycling of waste plastic polyethylene terephthalate(PET)waste bottles functionalized with carrollite CuCo_(2)S_(4) as a photothermal layer.Analytical characterization[X-ray diffraction(XRD),Fourier transform infrared spectroscopy(FTIR),and scanning electron microscopy-energy dispersive spectroscopy(SEM-EDS)]confirms the functionalization of carrollite CuCo_(2)S_(4) on graphitic carbon foam.The UV-Vis spectroscopy analysis showed an enhanced optical absorption in the UV-Vis-near IR region(>96%)for functionalized CuCo_(2)S_(4)-CF foam compared to carbon foam(67%).The interfacial solar desalination experiment presented a significantly enhanced evaporation rate of 2.4 kg·m^(−2)·h^(−1) for CuCo_(2)S_(4)-CF compared to that of CF(1.60 kg·m^(−2)·h^(−1))and that of CuCo_(2)S_(4)(1.60 kg·m^(−2)·h^(−1)).The obtained results proved that the newly synthesized CuCo_(2)S_(4)-CF from the upcycled plastic into new material for the photothermal desalination process can enhance the practice of a circular economy to produce fresh water.展开更多
文摘A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi （n = 10） and primary malignant melanomas （n = 10）, using quantitative real-time PCR. Differential expression was found for 72 microRNAs. Members of the let-7 family of microRNAs were significantly downregulated in primary melanomas as compared with benign nevi, suggestive for a possible role of these molecules as tumor suppressors in malignant melanoma. Interestingly, similar findings had been described for lung and colon cancer. Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1, D3, and A, and cyclin-dependent kinase （Cdk） 4, all of which had been described to play a role in melanoma development. The effect oflet-7b on protein expression was due to targeting of 3＇-untranslated regions （3＇UTRs） of individual mRNAs, as exemplified by reporter gene analyses for cyclin D1. In line with its downmodulating effects on cell cycle regulators, let-7b inhibited cell cycle progression and anchorage-independent growth of melanoma cells. Taken together, these findings not only point to new regulatory mechanisms of early melanoma development, but also may open avenues for future targeted therapies of this tumor.
文摘This study compared the efficacy of 70- and 120-w 2-μm thulium：YAG VapoEnucleation of the prostate （ThuVEP） for patients with benign prostatic obstruction （BPO）. A prospective analysis of 84 patients with symptomatic BPO and prostatic enlargement （t〉 60 ml） who underwent either 70-w （n=44） or 120-w ThuVEP （n=40） non-randomly was carried out. Patient demographics and perioperative and 12-month follow-up data were analysed. The mean prostate volume was 79.90---27.49 ml in patients who had received 70-w ThuVEP, which was less than in those who had received 120-w ThuVEP （88.53＋-25.10; P=0.033）. The mean enucleation （resected weight/laser time, 2.16±1.21 g min-1 vs. 1.23±0.60 g min-1; P=-0.013）, operation efficiency （resected weight/total operation time, 0.76±0.35 g min-1 vs. 0.42＋-0.27 g min-1; P=-0.000） and percentage of resected tissue （66.93%±22.79% vs. 45.41%±23.33%; P=-0.000） were higher with 120-w treatment compared to 70-w ThuVEP. One patient （1.2% of total patients） （in the 120-w group） required a blood transfusion postoperatively. Sixty-one patients （73%） were available for review at the 12-month follow-up time point. The quality of life （QoL）, International Prostate Symptom Score （IPSS）, maximum urinary flow rate （Qmax）, postvoiding residual urine （PVR） and prostate volume improved significantly after treatment （P≤ 0.035） and were not significantly different between those treated with the different devices （70- and 120-w）. The median prostate volume reduction was 81.70% and 82.19% with 70- and 120-w ThuVEP, respectively. The incidence of complications was low and did not differ between groups treated with the different devices. Two patients （2.4%） （one per group） had a bladder neck contracture at the follow-up. ThuVEP is a safe and efficacious procedure for the treatment of symptomatic BPO. The incidence of complications was low with both devices. The 120-w thulium：YAG device enhances the effectiveness of Th,VE
文摘AIM:To describe disease characteristics and treatment modalities in a group of rare patients with metastatic gastric carcinoid type 1(GCA1).METHODS:Information on clinical,biochemical,radiological,histopathological findings,the extent of the disease,as well as the use of different therapeutic modalities and the long-term outcome were recorded.Patients’data were assessed at presentation,and thereafter at 6 to 12 monthly intervals both clinically and biochemically,but also endoscopically and histopathologically.Patients were evaluated for the presence of specific symptoms;the presence of autoimmune disorders and the presence of other gastrointestinal malignancies in other family members were also recorded.The evaluation of response to treatment was defined using established WHO criteria.RESULTS:We studied twenty consecutive patients with a mean age of 55.1 years.The mean follow-up period was 83 mo.Twelve patients had regional lymph node metastases and 8 patients had liver metastases.The primary tumor mean diameter was 20.13±10.83mm(mean±SD).The mean Ki-67 index was 6.8%±11.2%.All but one patient underwent endoscopic or surgical excision of the tumor.The disease was stable in all but 3 patients who had progressive liver disease.All patients remained alive during the follow-up period.CONCLUSION:Metastatic GCA1 carries a good overall prognosis,being related to a tumor size of≥1 cm,an elevated Ki-67 index and high serum gastrin levels.
基金supported in part by a grant from National Natural Science Foundation of China 81470706a grant from Guangdong Natural Science Foundation No 2015A030313180
文摘Over the past two decades considerable progress has been made in understanding the ototoxic effects and mechanisms underlying loop diuretics. As typical representative of loop diuretics ethacrynic acid or furosemide only induces temporary hearing loss, but rarely permanent deafness unless applied in severe acute or chronic renal failure or with other ototoxic drugs. Loop diuretic induce unique pathological changes in the cochlea such as formation of edematous spaces in the epithelium of the stria vascularis, which leads to rapid decrease of the endolymphatic potential and eventual loss of the cochlear microphonic potential, summating potential, and compound action potential. Loop diuretics interfere with strial adenylate cyclase and Nat/Kt-ATPase and inhibit the Na-K-2Cl cotransporter in the stria vascularis, however recent reports indicate that one of the earliest effects in vivo is to abolish blood flow in the vessels supplying the lateral wall. Since ethacrynic acid does not damage the stria vascularis in vitro, the changes in Nat/Kt-ATPase and Na-K-2Cl seen in vivo may be secondary effects results from strial ischemia and anoxia. Recent observations showing that renin is present in pericytes surrounding stria arterioles suggest that diuretics may induce local vasoconstriction by renin secretion and angiotensin formation. The tight junctions in the blood-cochlea barrier prevent toxic molecules and pathogens from entering cochlea, but when diuretics induce a transient ischemia, the barrier is temporarily disrupted allowing the entry of toxic chemicals or pathogens.
文摘Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to estradiol ratio.In this subset of patients,and particularly in those with hypogonadism,elevated levels of circulating estradiol may establish a negative feedback on the hypothalamic–pituitary–testicular axis by suppressing follicle-stimulating hormone(FSH)and luteinizing hormone(LH)production and impaired spermatogenesis.Hormonal manipulation via different agents such as selective estrogen modulators or aromatase inhibitors to increase endogenous testosterone production and improve spermatogenesis in the setting of infertility is an off-label option for treatment.We carried out a systematic review and meta-analysis of the literature of the past 30 years in order to evaluate the benefits of the use of aromatase inhibitors in the medical management of infertile/hypoandrogenic males.Overall,eight original articles were included and critically evaluated.Either steroidal(Testolactone)or nonsteroidal(Anastrozole and Letrozole)aromatase inhibitors were found to statistically improve all the evaluated hormonal and seminal outcomes with a safe tolerability profile.While the evidence is promising,future prospective randomized placebo-controlled multicenter trials are necessary to better define the efficacy of these medications.
文摘BACKGROUND Prophylactic antibiotics have significantly led to a reduction in the risk of postoperative surgical site infections(SSI)in orthopaedic surgery.The aim of using antibiotics for this purpose is to achieve serum and tissue drug levels that exceed,for the duration of the operation,the minimum inhibitory concentration of the likely organisms that are encountered.Prophylactic antibiotics reduce the rate of SSIs in lower limb arthroplasty from between 4%and 8%to between 1%and 3%.Controversy,however,still surrounds the optimal frequency and dosing of antibiotic administration.AIM To evaluate the impact of introduction of a weight-adjusted antibiotic prophylaxis regime,combined with a reduction in the duration of administration of post-operative antibiotics on SSI incidence during the 2 years following primary elective total hip and knee arthroplasty METHODS Following ethical approval,patients undergoing primary total hip arthroplasty(THA)/total knee arthroplasty(TKA)with the old regime(OR)of a preoperative dose[cefazolin 2 g intravenously(IV)],and two subsequent doses(2 h and 8 h),were compared to those after a change to a new regime(NR)of a weight-adjusted preoperative dose(cefazolin 2 g IV for patients<120 kg;cefazolin 3g IV for patients>120 kg)and a post-operative dose at 2 h.The primary outcome in both groups was SSI rates during the 2 years post-operatively.RESULTS A total of n=1273 operations(THA n=534,TKA n=739)were performed in n=1264 patients.There was no statistically significant difference in the rate of deep(OR 0.74%(5/675)vs NR 0.50%(3/598);fishers exact test P=0.72),nor superficial SSIs(OR 2.07%(14/675)vs NR 1.50%(9/598);chi-squared test P=0.44)at 2 years postoperatively.With propensity score weighting and an interrupted time series analysis,there was also no difference in SSI rates between both groups[RR 0.88(95%CI 0.61 to 1.30)P=0.46].CONCLUSION A weight-adjusted regime,with a reduction in number of post-operative doses had no adverse impact on SSI incidence in this population.
文摘The homeoprotein encoded by the intestinal-specific Cdx2 gene is a major regulator of gut development and homeostasis,also involved in colon cancer as well as in intestinal-type metaplasias when it is abnormally expressed outside the gut.At the molecular level,structure/function studies have demonstrated that the Cdx2 protein is a transcription factor containing a conserved homeotic DNA-binding domain made ofthree alpha helixes arranged in a helix-turn-helix motif,preceded by a transcriptional domain and followed by a regulatory domain.The protein interacts with several thousand sites on the chromatin and widely regulates intestinal functions in stem/progenitor cells as well as in mature differentiated cells.Yet,this transcription factor also acts trough original nontranscriptional mechanisms.Indeed,the identification of novel protein partners of Cdx2 and also of a splicing variant revealed unexpected functions in the control of signaling pathways like the Wnt and NF-k B pathways,in double-strand break DNA repair and in premessenger RNA splicing.These novel functions of Cdx2 must be considered to fully understand the complexity of the role of Cdx2 in the healthy intestine and in diseases.
文摘Pet owner compliance is essential for the success of veterinary healthcare strategies. As some parasites are zoonotic, consistent parasite control is an integral part of the One-Health strategy. Highly palatable formulations help ensure compliance, as they offer a positive experience for the dog and the owner. This study was conducted to ascertain if dogs exhibited a preference between two commercially available oral formulations of broad-spectrum endectoparasiticides, NexGard Spectra (afoxolaner and milbemycin oxime) and Simparica Trio (sarolaner, moxidectin and pyrantel). For four consecutive days, 100 healthy dogs were offered both products and consumption was recorded. If one product was more consumed than the other, it was defined as the preferred product. No adverse event was recorded throughout the study. A total of 358 chewable tablets were consumed over four study days;78.5% of dogs voluntarily consumed NexGard Spectra (281 chews), while 21.5% of dogs voluntarily consumed Simparica Trio (77 chews, <i>p</i> < 0.01). Among 75 dogs which demonstrated a preference for a product, significantly more dogs preferred NexGard Spectra (94.7%) compared to Simparica Trio (5.3%) (<i>p</i> < 2.2 × 10<sup>-16</sup>), resulting in a preference ratio of 17.75 to 1 for NexGard Spectra.
文摘Objective To study the sensitivity and specificity of different staining methods to monitor apoptosis induced by oxidative stress in adherent cells.Methods Sensitivity and specificity of several common methods for apoptosis determination were evaluated (Apo2.7-expression, Annexin V-binding, TUNEL-reaction, poly-(ADP-ribose)-polymerase-(PARP) cleavage and single-stranded-DNA (ssDNA) staining). Apoptosis was induced by oxidative stress generated by hydrogen peroxide in 3 cultured cells types growing as adherent monolayer (MiaPaCa-2, Hep-G2 and human skin fibroblasts), necrosis was induced by depletion of cellular ATP using sodium azide. Cells positively stained by the respective apoptosis assay were quantified and alterations of cell morphology were monitored by fluorescence microscopy. The date was analyzed by one-way analysis of variance and significance test of correlation coefficient.Results One hour after apoptosis induction significant cell fractions were positively stained for ssDNA (33% with MiaPaCa-2 cells, 35% with Hep-G2 cells, 56% with human skin fibroblasts). PARP-cleavage was less sensitive compared to the ssDNA-staining. Apo2.7-expression, Annexin V-binding and TUNEL-reaction were not applicable to detect early apoptosis induced by oxidative stress (below 2 hours), but were efficiently monitoring late apoptosis. Specificity of ssDNA-staining was complete with each cell type even 4 hs after induction of necrosis by the highest sodium azide concentration. In contrast, the same experimental conditions resulted in 50%-90% positively stained necrotic cells by using Apo2.7-expression, TUNEL-reaction or AnnexinV-binding. Surprisingly, specificity of PARP-cleavage was highly depending on the respective cell type.Conclusions Our study prove that among the five methods investigated only ssDNA-staining allowed to completely differentiate apoptosis from necrosis, and is thus suitable to reliably detect early as well as late apoptosis. Therefore, the ssDNA-staining may be used as reference method to clearly ide
基金This work was supported by The National Natural Science Foundation of China （Grant Nos. 21177027 and 41275126）, Ministry of Science and Technology of China （2012YQ220113-4）, the Science ＆ Technology Commission of Shanghai Municipality （12DJ1400100, 14XD 1400600）, and the Jiangsu Provincial Collaborative Innovation Center of Climate Change.
文摘Fresh straw burning （SB） particles were generated in the laboratory by the combustion of rice straw and corn straw. The chemical composition and mixing state of the fresh SB particles were investigated by an Aerosol Time-of-Flight Mass Spectrometer （ATOFMS）. Based on the mass spectral patterns, the SB particles were clustered into four major types： Salt, Organic Carbon （OC）, Elemental Carbon （EC）, and internally mixed particles of EC and OC （EC-OC）. In addition, particles containing ash, polycyclic aromatic hydrocarbons, heavy metals or nicotine were also observed. Physical and chemical changes of the SB particles immediately after the emission were analyzed with highly time-resolved data. During the aging processes, the average particle size increased steadily. Freshly emitted organic compounds were gradu- ally oxidized to more oxygenated compounds in the OC- containing particles. Meanwhile, an important displace- ment reaction （2KCI＋ SO24- KzSO4 ＋ 2C1-） was observed. The marker ions for SB particles were optimized and applied to identify the SB particles in the ambient atmosphere. The fluctuation of the number fraction of ambient SB particles sorted by ATOFMS agrees well with that of water soluble K＋ measured by an online ion chromatography, demonstrating that the optimized marker ions could be good tracers for SB particles in field measurements.
基金supported by the Federal State of Thuringia(2017 FGR 0076)the European Social Fund(ESF)+1 种基金the Thüringer Aufbaubank(TAB)for funding the junior research group HOROS(FKZ:2017 FGR 0076)the European Research Council(ERC)under the European Union’s Horizon 2020 research and innovation programm(grant agreement No.[835306],SALT)。
文摘Microscopy with extreme ultraviolet(EUV)radiation holds promise for high-resolution imaging with excellent material contrast,due to the short wavelength and numerous element-specific absorption edges available in this spectral range.At the same time,EUV radiation has significantly larger penetration depths than electrons.It thus enables a nano-scale view into complex three-dimensional structures that are important for material science,semiconductor metrology,and next-generation nano-devices.Here,we present high-resolution and material-specific microscopy at 13.5 nm wavelength.We combine a highly stable,high photon-flux,table-top EUV source with an interferometrically stabilized ptychography setup.By utilizing structured EUV illumination,we overcome the limitations of conventional EUV focusing optics and demonstrate high-resolution microscopy at a half-pitch lateral resolution of 16 nm.Moreover,we propose mixed-state orthogonal probe relaxation ptychography,enabling robust phase-contrast imaging over wide fields of view and long acquisition times.In this way,the complex transmission of an integrated circuit is precisely reconstructed,allowing for the classification of the material composition of mesoscopic semiconductor systems.
基金This work was supported by the Marie Skłodowska-Curie Individual Fellowship(No.GA 101027930)the Italian Ministry of University(MUR)for funding through Progetti di Ricerca Scientifica di Rilevante Interesse Nazionale(No.2022FNL89Y)+2 种基金the Kempe Foundation,the Knut&Alice Wallenberg Foundationthe Project of Ca’Foscari University of Venice(SPIN Project)the National Recovery and Resilience Plan(NRRP),Mission 4 Component 2 Investment 1.3,Project NEST.
文摘Interfacial solar desalination is an emerging technology for freshwater production,but the finding of novel solar evaporators is still challenging.In the present research,graphitic carbon foam(CF)was synthesized from the upcycling of waste plastic polyethylene terephthalate(PET)waste bottles functionalized with carrollite CuCo_(2)S_(4) as a photothermal layer.Analytical characterization[X-ray diffraction(XRD),Fourier transform infrared spectroscopy(FTIR),and scanning electron microscopy-energy dispersive spectroscopy(SEM-EDS)]confirms the functionalization of carrollite CuCo_(2)S_(4) on graphitic carbon foam.The UV-Vis spectroscopy analysis showed an enhanced optical absorption in the UV-Vis-near IR region(>96%)for functionalized CuCo_(2)S_(4)-CF foam compared to carbon foam(67%).The interfacial solar desalination experiment presented a significantly enhanced evaporation rate of 2.4 kg·m^(−2)·h^(−1) for CuCo_(2)S_(4)-CF compared to that of CF(1.60 kg·m^(−2)·h^(−1))and that of CuCo_(2)S_(4)(1.60 kg·m^(−2)·h^(−1)).The obtained results proved that the newly synthesized CuCo_(2)S_(4)-CF from the upcycled plastic into new material for the photothermal desalination process can enhance the practice of a circular economy to produce fresh water.
