19% in those without anal condylomata) Having anal condylomata w

19% in those without anal condylomata). Having anal condylomata was associated with higher prevalences of cytological abnormalities (83% vs. 32% in those without anal condylomata; OR 6.9; 95% CI 3.8–12.7) and high-grade squamous intraepithelial lesions (HSILs) (9% vs. 3% in those without

anal condylomata; OR 9.0; 95% CI 2.9–28.4) in the anal canal. HIV-infected men with anal condylomata were at risk of presenting HSILs and harbouring multiple HR HPV infections in the anal canal. Although MSM presented the highest prevalence of anal condylomata, heterosexual men also had a clinically important prevalence. Our findings emphasize the importance of screening and follow-up for condylomata in the anal canal in HIV-infected men. Human papillomavirus (HPV) types that infect the ano-genital tract can be divided into low-risk (LR) HPV types, RAD001 solubility dmso which are associated with Selleck FK866 the development of ano-genital condylomata,

and high-risk (HR) HPV types, which are implicated in the evolution of anal squamous cell cancer and its putative precursor, high-grade anal intraepithelial neoplasia (AIN) [1-3]. The association between genital warts and the presence of HPV infection has been widely described [4, 5]. Genital condylomata are benign lesions usually resulting from infection by HPV-6 or HPV-11. In contrast, HPV-16, HPV-18 and HPV-31 are associated with the development of high-grade dysplasia or carcinoma [5-7]. Cervical cytology is the most appropriate means of screening for precancerous lesions

and cervical HPV-related cancer [8]. Currently, anal cytology is used as a screening tool for anal squamous lesions to detect AIN or anal cancer at an earlier stage [9, 10]. It is known 3-mercaptopyruvate sulfurtransferase that HIV-associated immunosuppression may increase the likelihood of development of both low-grade and high-grade HPV-related lesions. In addition, the longer life expectancies of the HIV-positive population as a result of highly active antiretroviral therapy may permit established high-risk HPV infections to progress to anal cancer [11]. The transmission of HPV depends on sexual behaviour, and HPV infection is strongly related to the lifetime number of sexual partners as well as to the practice of receptive anal intercourse (RAI) in men having sex with men (MSM) [12]. The HIV-positive population, and in particular MSM, have a high risk of developing anal condylomata and precancerous lesions or ano-genital neoplasia [13]. Most condylomata lesions will spontaneously resolve in the immunocompetent population, but immune-compromised patients with condylomata (especially HIV-infected patients) generally require therapy that is painful and expensive, and also have a high risk of recurrence [14-16].

Comparison of changes in the lipopolysaccharides profiles of the

Comparison of changes in the lipopolysaccharides profiles of the wild-type and mutant strains lends further credence to this possibility PD0325901 concentration because differences in the lipopolysaccharides

profiles were seen to occur for all strains, but at different times during the flocculation process. Therefore, the mutant strains lacking cheA1 or cheY1 may be affected in the timing of flocculation, which may result, for example, from an increased sensitivity of the cells to the cues that trigger flocculation or perhaps to other effects. Structural and other differences identified between the flocs formed by ΔcheA1 and ΔcheY1 strains thus collectively suggest that the function of Che1 in modulating flocculation is indirect. Taken together and with data from the literature (Burdman et al., 2000a; Bahat-Samet et al., 2004; Bible et al., 2008), the results obtained here underscore the significant changes of the cell surface and extracellular matrix that occur during flocculation and support a model in which flocculation in A. brasilense is an adaptive behavior CX-4945 solubility dmso that allows the cells to

differentiate into resistant forms via extensive remodeling of the cell surface and the extracellular matrix, including lipopolysaccharides and exopolysaccharide. The authors would like to thank Dave Allison for helpful discussions. This research was funded by the Genomic Science Program of the Office of Biological and Environmental Research, US DOE, and NSF MCB-0919819 to G.A. Oak Ridge National Laboratory is managed by UT-Battelle, LLC, for the US Department of Energy under Contract no. DE-AC05-00OR22725. A.N.E. and P.S. contributed equally to this work. Fig. S1. AFM 5×5 μm deflection scans of wild-type and mutant strains. Fig. S2. AFM topography images of (a) wild-type Sp7; (b) AB101 (ΔcheA1); (c) AB102 (ΔcheY1). Table S1. Quantification of lectin binding. Please

note: Wiley-Blackwell is not responsible for the content PRKACG or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. “
“Streptococcus suis serotype 2 (SS2) infection is a major cause of sudden death in pigs and is of concern for humans as it has strong zoonotic capabilities. Developing novel effective vaccines would be beneficial to control SS2 infection. HP0272 is a novel immunogenic surface protein; its protective efficacy remains to be evaluated. The present mouse model found that the purified recombinant HP0272 could elicit a significant humoral antibody response, and to confer complete protection against a lethal dose of SS2 infection. In addition, real-time PCR confirmed that in vivo-induced antigen existed in most SS2 field pathogenic strains, and in half of all reference strains of different serotypes of S. suis.

, 2010) All putative zinc-binding partners of both methyltransfe

, 2010). All putative zinc-binding partners of both methyltransferases are located in the catalytic domains of the enzymes (Fig. 3). Although the MT I mediate a similar reaction in A. dehalogenans, the putative zinc-binding amino acids as well as their position in the primary protein structure are different. Both MT I do not have the common binding motifs described for enzymes with similar functions such as the methionine synthases of E. coli (Peariso et al., 1998; Zhou et al., 1999). Usually, the distance between two of the three binding ligands is not larger than three amino acid residues and the third binding partner is separated

from these two amino acids by a longer distance (Vallee & Auld, 1990a). Both MT I of A. dehalogenans show unique zinc-binding motifs: E-X14-E-X20-H for MT Ivan

Decitabine research buy and D-X27-C-X39-C for MT Iver. Cysteine does not seem to be involved in zinc binding in MT Ivan. All other corrinoid-dependent methyltransferases investigated so far involve cysteine as a ligand for zinc (Peariso et al., 1998; Krüer et al., 2001; Hagemeier et al., 2006). MT Ivan only contains Selleckchem INK128 one cysteine residue (C286). When this residue was exchanged to alanine, zinc was still present and the enzyme was active. In principle, it cannot be excluded that the exchange of an amino acid might result in a conformation change of the protein and thus may be responsible for the loss of the zinc and activity. However, the controls performed by exchanging adjacent amino acids or shifting the position of the putative binding amino acid cysteine (MT Iver) by ±1 are in favor of the proposed zinc-binding sites. In the methanol methyltransferase MtaB of M. barkeri, zinc is bound to two cysteine residues and one glutamate residue (Hagemeier et al., 2006). The zinc-binding motif also differs from the common motifs and is described as E-X55-C-X48-C. It is therefore feasible that the corrinoid-dependent, zinc-containing methyltransferases have in common that they contain zinc-binding motifs different from those of other zinc enzymes. Besides the zinc-binding

amino acids, acidic amino acids were exchanged to alanine in both MT I to investigate their influence on the catalysis (Fig. 2). The restricted activities of the mutants obtained suggest an involvement of these negatively charged amino acids in the demethylation of the substrate and/or the transfer of the methyl group to the CP. For MtaB of M. barkeri, the analysis of the crystal structure also exhibits acidic amino acids close to the zinc-binding motif (Hagemeier et al., 2006). For these residues, a polarization of methanol and an enhancement of the charge density of zinc have been proposed, which supports cleavage of the substrate (Hagemeier et al., 2006). A similar function is suggested for the acidic amino acid residues of the MT I of A. dehalogenans. This work was supported by grants from the Deutsche Forschungsgemeinschaft.

Long-term potentiation and long-term depression, long held as the

Long-term potentiation and long-term depression, long held as the principal means of producing lasting change in cerebral circuits, are easily induced in the hippocampus (Bliss & Lomo, 1973; Dudek & Bear, 1992) but are more difficult to produce in the cortex (Trepel & Racine, 1998). Induction of synaptic plasticity in the cortex requires multiple sessions of tetanising trains to be CCI-779 nmr effective and reflects the relative stability of neocortical circuits. While the mechanisms underlying the ability of tDCS to produce lasting neural changes in these circuits have not yet been fully established (see Stagg & Nitsche, 2011; Márquez-Ruiz et al.,

2012), the number of sessions required for recovery is probably due to tDCS overcoming cortical resistance to synaptic plasticity, a delay period in the accumulation of critical Inhibitor Library chemical structure neuromodulators or growth factors (e.g., brain-derived neurotrophic factor; Fritsch et al., 2010),

or both. Recovery was only observed to more peripherally located visual targets, and this finding may reflect a limited capacity of the tDCS to penetrate into the depths of the cortex. The targeted cortex is retinotopically organised: the representation of the contralateral peripheral visual field is located near the skull on the crest of each gyrus, and the neurons in the fundus of the sulcus represent central and pericentral locations (Palmer et al., 1978). The behavioral results, therefore, may reflect a selective reduction in activity or in the firing probability of the neurons that represent peripheral targets Carteolol HCl and that are located closer to the skull. The results also may reflect selective activation of neurons in this cortex whose somatodendritic or axonal axes is optimally oriented to the electric field (e.g., Bikson et al., 2004; Radman et al., 2009; Kabakov et al., 2012). The behavioral results

also indicate that the resting membrane potential of neurons near the depth of the sulcus, which correspond to central visual field locations (Palmer et al., 1978), may not be sufficiently modulated by tDCS to produce a behavioral change. In as much as functional alterations in these neurons are the basis for the recovery, this result runs counter to predictions of modeling studies that show a preferential effect of tDCS on neurons at the bases of sulci (Miranda et al., 2013). Moreover, the present results suggest that the tDCS-mediated reduction in activity also does not feed down to neurons in the depth of the sulcus through substantial intra-areal circuits demonstrated to fill this region (Norita et al., 1996). Further modeling of tDCS currents and biological study is required to provide a definitive answer to the mechanisms and the precise neuronal elements underlying the present results. It is notable that one animal did not respond to tDCS treatment. Examination of the lesion showed no identifiable differences in terms of size or extent of lesion.

DNA fragments of similar size but varying sequence migrate throug

DNA fragments of similar size but varying sequence migrate through an increasing gradient of formamide and urea with constant mobility until the fragment with the lowest melting point dissociates. Fragments of similar

size but with base-pair substitutions affect the melting point sufficiently H 89 datasheet to effect separation. Larger DNA fragments would transition to partially melted form, while the higher-melting-point domains would remain helical. By attaching a GC clamp at one end, the melting point of the terminal domain is sufficiently higher than the rest, allowing for detection of single-base substitutions (Myers et al., 1985b). The slight differences in stacking interactions between adjacent bases cause melting at slightly different denaturant concentrations. Initial GC clamps were 300 bp in length, and later workers developed shorter clamps, down to 40 bp (Sheffield et al., 1989). Introduction of shorter GC clamps into a gene sequence was facilitated using 5′-GC-tailed

primers and PCR. Using proper conditions, the attachment of a GC clamp can increase the detection of single base-pair selleck changes to near 100% (Myers et al., 1985a; Sheffield et al., 1989). DGGE was first applied to the study of bacterial diversity in the early 1990s (Muyzer et al., 1993). These authors combined the amplification of 16S rRNA gene pools using primers directed at conserved regions with introduction of a 40-bp GC clamp and DGGE. This approach allowed the study of complex microbial populations without the requirement for laborious processes such as culturing or clonal sequencing, both of which have been shown to have a number of limitations (Hugenholtz et al., 1998; Dunbar et al., 1999; Leser et al., 2002).

DGGE is not devoid of limitations, but the relative ease and apparent effectiveness has lead to increased use in the study of microbial communities (Muyzer & Smalla, 1998; Fromin et al., 2002; Nakatsu, 2007). During the use of DGGE for several projects, we began to suspect variation between repeat sets of equivalent GC-clamp primers. We hypothesized Histone demethylase that repeat syntheses of identical 40-base GC-clamp primers lead to different DGGE profiles. This study was undertaken to interrogate the effect of repeat sets of GC-clamp primers on DGGE profiles. Bacterial DNA was extracted from two different corn fields (C and U) at Aurora (eastern South Dakota) using the PowerSoil DNA Isolation Kit (MoBio Laboratories Inc.). Genomic DNA of Escherichia coli K12, Bacillus subtilis 168, and Arthrobacter aurescens was extracted using the Microbial DNA Isolation kit (MoBio Laboratories Inc.). PCR of the V3–5 region of the bacterial 16S rRNA genes was performed using primer F357 (Muyzer et al., 1993), with one of two 5′ forty-base GC clamps (Muyzer et al.

All data are expressed as the means and standard deviations of th

All data are expressed as the means and standard deviations of three determinations per experimental condition. Statistical significance was determined using a one-way anova followed by Dunnett’s multiple comparison test. A P-value < 0.05 was considered statistically significant. The T3SS-associated chaperone and the effector complex

bind to each other with high affinity (Luo et al., 2001). Therefore, we used ZVADFMK a screening assay using T3SS2 effectors fused with GST to pull down chaperone candidates. The amino-terminal regions of T3SS2 effectors (VopC, VopL, VopP, and VopT) fused to the CyaA (Bordetella pertussis toxin) catalytic domain can be injected into host cells (Kodama et al., 2007) (T. Kodama, unpublished data). This is consistent with other T3SS effectors and suggests that the amino-terminal regions of V. parahaemolyticus T3SS2 effectors are sufficient for efficient secretion and translocation. In general, amino-terminal domains (1–200 amino acids) of T3SS effectors contain the amino-terminal secretion signal of the T3SS and the chaperone-binding domains, which are both essential for effector secretion

(Feldman & Cornelis, 2003; Parsot et al., 2003). Plasmids expressing the selleck chemicals llc amino-terminal domains (1–200 amino acids) of the T3SS2 effectors VopC, VopL, VopP, and VopT fused to GST were introduced into V. parahaemolyticus knockout strains for each gene. The GST fusions expressed in V. parahaemolyticus strains were purified using glutathione beads and separated using SDS-PAGE. The molecular weights of most T3SS-associated chaperones are less than 20 kDa (Feldman & Cornelis, 2003;

Parsot et al., 2003); therefore, the areas containing proteins of these molecular weights were carefully observed. Although the T3SS2 effectors fused to GST appeared to be unstable (a lower amount of T3SS2 effector fusions than breakdown products was observed), the amino-terminal 1–200 amino acids of the T3SS2 effectors fused to GST were copurified with a specific band that was not observed in the negative control (GST alone), as shown in Fig. 1a. Mass analysis revealed proteins interacting with GST–VopC1–200, GST–VopL1–200, and GST–VopT1–200 (Fig. 1b), while GST–VopP1–200 did not interact with any specific proteins that could be chaperone candidates. The results suggested that only one protein encoded Florfenicol in the Vp-PAI, VPA1334 (designated VocC; Vop chaperone C), appeared to be a T3SS chaperone candidate. The molecular weight and the isoelectric point of VocC were estimated as 14.3 kDa and 5.41, respectively. Based on the information from previously identified T3SS-associated chaperones (Feldman & Cornelis, 2003; Parsot et al., 2003), these values indicate that VocC is a possible T3SS2-associated chaperone for VopC, VopL, and VopT, and this result may categorize VocC as a type IB class chaperone, which chaperones multiple effectors (Parsot et al., 2003).

All data are expressed as the means and standard deviations of th

All data are expressed as the means and standard deviations of three determinations per experimental condition. Statistical significance was determined using a one-way anova followed by Dunnett’s multiple comparison test. A P-value < 0.05 was considered statistically significant. The T3SS-associated chaperone and the effector complex

bind to each other with high affinity (Luo et al., 2001). Therefore, we used selleck chemical a screening assay using T3SS2 effectors fused with GST to pull down chaperone candidates. The amino-terminal regions of T3SS2 effectors (VopC, VopL, VopP, and VopT) fused to the CyaA (Bordetella pertussis toxin) catalytic domain can be injected into host cells (Kodama et al., 2007) (T. Kodama, unpublished data). This is consistent with other T3SS effectors and suggests that the amino-terminal regions of V. parahaemolyticus T3SS2 effectors are sufficient for efficient secretion and translocation. In general, amino-terminal domains (1–200 amino acids) of T3SS effectors contain the amino-terminal secretion signal of the T3SS and the chaperone-binding domains, which are both essential for effector secretion

(Feldman & Cornelis, 2003; Parsot et al., 2003). Plasmids expressing the PD-332991 amino-terminal domains (1–200 amino acids) of the T3SS2 effectors VopC, VopL, VopP, and VopT fused to GST were introduced into V. parahaemolyticus knockout strains for each gene. The GST fusions expressed in V. parahaemolyticus strains were purified using glutathione beads and separated using SDS-PAGE. The molecular weights of most T3SS-associated chaperones are less than 20 kDa (Feldman & Cornelis, 2003;

Parsot et al., 2003); therefore, the areas containing proteins of these molecular weights were carefully observed. Although the T3SS2 effectors fused to GST appeared to be unstable (a lower amount of T3SS2 effector fusions than breakdown products was observed), the amino-terminal 1–200 amino acids of the T3SS2 effectors fused to GST were copurified with a specific band that was not observed in the negative control (GST alone), as shown in Fig. 1a. Mass analysis revealed proteins interacting with GST–VopC1–200, GST–VopL1–200, and GST–VopT1–200 (Fig. 1b), while GST–VopP1–200 did not interact with any specific proteins that could be chaperone candidates. The results suggested that only one protein encoded second in the Vp-PAI, VPA1334 (designated VocC; Vop chaperone C), appeared to be a T3SS chaperone candidate. The molecular weight and the isoelectric point of VocC were estimated as 14.3 kDa and 5.41, respectively. Based on the information from previously identified T3SS-associated chaperones (Feldman & Cornelis, 2003; Parsot et al., 2003), these values indicate that VocC is a possible T3SS2-associated chaperone for VopC, VopL, and VopT, and this result may categorize VocC as a type IB class chaperone, which chaperones multiple effectors (Parsot et al., 2003).

Streptococcus pneumoniae produced three bands at 55, 150 and 200 

Streptococcus pneumoniae produced three bands at 55, 150 and 200 bp (Fig. 5a, lane 3). Streptococcus agalactiae (lane 2) and S. suis (lane 4) gave similar pattern. Thus, the LAMP products of S. agalactiae and S. suis were further digested with HaeIII. The result showed that S. agalactiae was digested into four bands at 70, 216, 254 và 292 bp (Fig. 5b, lane 6), while S. suis was not digested by HaeIII (Fig. 5b, lane 5). To our knowledge, this is the first study that developed a broad range LAMP assay for simultaneous detection of more than four different bacterial species. The sensitivity of our LAMP assay was 100–1000 times higher compared with the conventional PCR assay. The

bacterial species could be distinguished among S. pneumoniae, S. suis, S. agalactiae and S. aureus based on

the digested pattern BMN 673 in vivo of the LAMP products with restriction enzymes of DdeI and HaeIII. In addition, our method has http://www.selleckchem.com/products/idasanutlin-rg-7388.html several advantages over the current diagnostic methods. Firstly, the method is rapid (c. 1 h) as compared with the real-time PCR method which requires 6 h to run (Nadkarni et al., 2002). Secondly, the LAMP method does not require expensive fluorimeter and fluorogenic primers and probes. Thirdly, the assay is simple and does not require highly experienced technician. More importantly, the assay can be performed in a water bath at bedside or in rural areas. These advantages suggested that our broad range LAMP assay would improve the early diagnosis and treatment of BM, helping to reduce morbidity and mortality.

Furthermore, the assay could detect bacterial species, helping to select an appropriate antibiotic therapy. One limitation of our LAMP assay was that only four species could be detected. A single-tube LAMP assay for the detection of more than four species is under development using a mixture current broad range LAMP primers and specific LAMP primers of other bacteria species. Additional Methocarbamol clinical studies are also required to validate this new assay. Four common pathogen of BM including S. pneumoniae, S. suis, S. agalactiae and S. aureus could be simultaneously detected using a broad range LAMP assay in single tube in < 1 h. The assay is highly sensitive, rapid and simple and can be performed at bedside in healthcare facilities. We thank Dr Toru Kubo, from Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan, for his technical advice. The authors declare no competing interests of the manuscript due to commercial or other affiliations. This study was supported in part by Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) for K.H. N.T.H and L.T.T.H. contributed equally to this work. "
“The extracellular haem-binding protein from Streptomyces reticuli (HbpS) has been shown to be involved in redox sensing and to bind haem. However, the residues involved in haem coordination are unknown.

Around a quarter

Around a quarter Vemurafenib of heterosexuals attended a non-local service [25% (2073/8404) and 23% (3320/14747) among men and women, respectively] compared with 22% (201/916) of injecting drug users (IDUs) (χ2 for all risk groups P<0.01). Black-African and Black-Caribbean patients were less likely to attend a non-local service compared with White patients [23% (3888/16 897), 26% (367/1431) and 29% (6711/23 416), respectively; χ2P<0.01]. Older patients were more likely to attend a non-local service than younger patients [28% (5517/19 612) of 40–54-year-olds vs. 21% (375/1755) of 15–24-year-olds;

χ2P<0.01]. Patients living more than 5 km from an HIV service were more likely to use a non-local service compared with patients living within 5 km of a service [36% (3252/9010) vs. 24% (9092/37 540), respectively; χ2P<0.01], as were patients living in urban areas compared with those living in rural areas [44% (930/2130) vs. 26% (11 414/44 420), respectively; χ2P<0.01]. Adults living in the least deprived areas were twice as likely to attend non-local services as those living in the most deprived areas [42% (1185/2798) vs. 21% (4162/19 461), respectively; χ2P<0.01]. Patients prescribed ART drugs were more likely to use a non-local service compared with those not prescribed ART

drugs [28% (9243/33 117) vs. 23% (2766/12 233), respectively]. Patients who first attended PD332991 services in 2007 were less likely to attend a non-local service compared with those who attended services before 2007 [20% (1192/5962) vs. 27% (11 152/40 588), respectively; χ2P<0.01]. In a multivariable analysis, the strongest predictor of travelling to non-local care was residential deprivation. Patients ZD1839 cell line living in the least deprived areas were more than twice as likely to access non-local services compared with those living in the most deprived areas (AOR 2.6; 95% CI 1.98–2.37). Those who first attended HIV care before 2007 were 50% more likely to attend non-local sites compared with those who first attended for care in 2007 (AOR 1.48; 95%

CI 1.38–1.59). Patients living in urban areas were 23% more likely to use non-local services compared with those living in rural areas (AOR 0.77; 95% CI 0.69–0.85) (Table 2). Other predictors that retained their significance in the multivariable model included risk group, receipt of ART, age and ethnicity. Patients infected through blood/blood products were almost twice as likely to attend non-local services as MSM (AOR 1.99; 95% CI 1.61–2.45). Patients aged 40–54 years were 29% more likely to use non-local services compared with those aged 15–24 years (AOR 1.26; 95% CI 1.10–1.43). Finally, patients who received ART were 24% more likely to use non-local services compared with those not receiving ART (AOR 1.24; 95% CI 1.17–1.30) (Table 2).

The cumulative results of these studies reported that

lym

The cumulative results of these studies reported that

lymphadenectomy did not improve disease-free survival (pooled hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.96–1.58) and overall survival (pooled HR, 1.07; 95% CI, 0.81–1.43).[6, 7] These findings should be interpreted with caution, however, because of several pitfalls in the study design of both trials. First, they included a large proportion of low-risk women, which diluted the possible therapeutic effects of lymphadenectomy. Given the low rate of lymphatic spread in the early stage of disease (9%–13%), it is not surprising that the two trials SB525334 mouse failed to find any therapeutic role for pelvic lymphadenectomy in the low-risk population. Second, no clear indication was given for postoperative adjuvant therapy. One of the

main goals of lymphadenectomy MAPK Inhibitor Library in vitro is to tailor adjuvant treatment to decrease radiation-related morbidity in patients with negative nodes. However, the adjuvant therapy administration rate was similar in both study arms; this result obviously influenced postoperative outcomes. Third, neither trial evaluated appropriately the role of para-aortic lymphadenectomy. In patients with lymphatic spread, para-aortic node involvement occurs in 60% of patients with endometrioid EC and 70% of those with non-endometrioid EC.[8] Therefore, the performance of pelvic lymphadenectomy alone represents an incomplete surgical effort because of the partial removal of metastatic nodes. Additionally, in the ASTEC trial,[7] the number of pelvic nodes yielded was low in many of the patients. The median

number of pelvic nodes harvested was 12 (range, 1–59); moreover, in the lymphadenectomy arm, 241 women (35%) had nine or fewer nodes and 72 women (12%) had four or fewer nodes. Recently, in response to the current evidence that pelvic lymphadenectomy alone did not provide any significant benefit on EC, Todo et al.[9] designed a retrospective cohort TCL analysis (the SEPAL study) aimed at assessing the role of para-aortic lymphadenectomy. The authors compared outcomes of patients undergoing systematic pelvic lymphadenectomy or combined pelvic and para-aortic lymphadenectomy in intermediate- and high-risk EC patients. The SEPAL study showed that high-risk patients who had pelvic and para-aortic lymph node dissection experienced a longer overall survival than patients who had pelvic lymphadenectomy alone (HR, 0.53; 95% CI, 0.38–0.76; P < 0.001).