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luations of the 7 tasks. Three tasks (i.e., creation of the bladder flap, colpotomy, and closure of the vault) revealed sound validity evidence, including at the level of the attending surgeon, whereas other tasks were more consistent with low-stakes formative evaluation standards.

The aim of this study was to investigate the prevalence of ceftazidime/avibactam (CZA) resistance among carbapenemase-producing Enterobacterales (CPE) blood culture isolates as well as the performance of the main carbapenemase phenotypic detection methods to identify KPC variants associated with CZA resistance.

Non-duplicate CPE strains isolated from blood cultures during 2018-2020 were tested for antimicrobial susceptibility. Molecular testing was used to identify carbapenemase-producers. Strains harbouring bla

and with a CZA minimum inhibitory concentration (MIC) ≥8 mg/L were investigated by sequencing. Subsequentially, five phenotypic carbapenemase detection methods were evaluated on these strains, namely the modified carbapenem inactivation method (mCIM), Rapidec® Carba NP, the disk diffusion synergy test, NG-Test CARBA® 5 and RESIST-5 O.O.K.N.V.

Overall, the CZA resistance rate was high (13.7%) and remained relevant (5.9%) excluding metallo-β-lactamases-producers. All isolates harbouringbla

mut CZA resistance.

This study was conducted to evaluate the efficacy and safety of eravacycline, a recently approved fluorocycline for treatment of complicated intra-abdominal infections (cIAIs).

PubMed, EMBASE and three trial registries were searched for randomised controlled trials (RCTs) comparing the efficacy and safety of eravacycline versus comparators. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using random-effects models. The study outcomes included clinical response, all-cause mortality and adverse events (AEs).

Three RCTs (1128 patients) with cIAIs were included. There were no significant differences in clinical response in the modified intention-to-treat (ITT) (OR, 0.91, 95% CI 0.62-1.35; I

= 0%), microbiological ITT (OR, 0.93, 95% CI 0.61-1.41; I

= 0%) and clinically evaluable (OR, 0.98, 95% CI 0.55-1.75; I

= 0%) populations or in all-cause mortality (OR, 1.18, 95% CI 0.16-8.94; I

= 0%). Eravacycline was associated with significantly greater odds of total AEs (OR, 1.55, 95% CI 1.20-1.99; I

= 0%) and nausea (OR, 5.29, 95% CI 1.77-15.78; I

= 1.70%) but the increase in vomiting was non-significant (OR, 1.44, 95% CI 0.73-2.86; I

= 1.70%). There were no significant differences in serious AEs or discontinuation due to AEs.

This meta-analysis of RCTs found similar clinical efficacy and mortality for eravacycline compared with carbapenems for treatment of cIAIs. However, the odds of total AEs and specifically nausea was higher with eravacycline, while no significant differences were observed in vomiting (although numerically higher), serious AEs or discontinuation due to AEs.

This meta-analysis of RCTs found similar clinical efficacy and mortality for eravacycline compared with carbapenems for treatment of cIAIs. However, the odds of total AEs and specifically nausea was higher with eravacycline, while no significant differences were observed in vomiting (although numerically higher), serious AEs or discontinuation due to AEs.Arsenic is a metalloid that has been hypothesized to be an environmental risk factor for Alzheimer's disease (AD), a disease having hyperphosphorylated tau aggregate as a marker. The present study demonstrated that prolonged exposure to sodium arsenite at low micromolar range (1-10 μM) reduced Tau 1 (recognizing dephosphorylated tau at residues 189-207) and elevated pS202 tau in differentiated human neuroblastoma SH-SY5Y cells indicating that arsenic increases tau phosphorylation in neurons. Sodium arsenite elevated GSK3β kinase activity, while GSK3 inhibitors, BIO, SB216763, and lithium, reversed the Tau 1 reduction by sodium arsenite. Additionally, sodium arsenite increased levels of active phosphorylation of ERK1/2, and inhibition of ERK1/2 by U0126 partially improved the Tau1 reduction. These results suggest that arsenic may cause tau hyperphosphorylation in neurons through the activation of GSK3 and ERK1/2. Furthermore, sodium arsenite augmented tau phosphorylation in the membrane and cytosolic fractions. Inductions of GSK3 activity by sodium arsenite treatment were observed in the membrane fraction, as evidenced by a reduction of β-catenin, a protein signaled for degradation following phosphorylation by GSK3. An enhancement of ERK1/2 phosphorylation by sodium arsenite was also witnessed in the cytosol. Additionally, sodium arsenite increased insoluble tau aggregation. These results suggest that arsenic induces tau hyperphosphorylation in the membrane fraction which may lead to its redistribution from the membrane fraction to the cytosol, where it promotes neurofibrillary formation. Collectively, we demonstrate that prolonged arsenic exposure increases tau phosphorylation, partly through GSK3 and ERK1/2 activation, and insoluble tau aggregates, hence possibly contributing to the development of sporadic AD.The aberrant micro-RNA (miR) expression has been reported to play a vital role in proliferation and tumorigenesis and of several human cancers. MicroRNA-365 (miR-365) has been shown to exhibit tumor-suppressive or oncogenic role in several human cancers. Nonetheless, little is known about its growth regulatory role in human multiple myeloma. The present study characterized the regulatory control exercised by miR-365 in multiple myeloma. The results showed significant (P  less then  0.05) upregulation of miR-365 in myeloma tissues and cell lines. Overexpression of miR-365 significantly (P  less then  0.05) suppressed the proliferation and inhibition of miR-365 promoted the proliferation of the human myeloma cells. The tumor-suppressive effects of miR-365 were found to be the result of apoptosis in the IM-9 myeloma cells. The miR-365 overexpression also suppressed the invasion of the IM-9 myeloma cells. The homeobox gene, HOXA9 was identified as the molecular regulatory target of miR-365 in human myeloma. The overexpression of miR-365 was shown to cause suppression of HOXA9. The silencing of HOXA9 could also suppress the growth of the IM-9 myeloma cells while as the overexpression of HOXA9 could abolish the tumor-suppressive effects of miR-365. The in vivo study revealed that miR-365 inhibits the growth of the xenografted tumors. Nonetheless, the inhibition of miR-365 promotes the growth of the xenografted tumors. To sum up, the current study suggests the tumor-suppressive effects of miR-365 in human myeloma and highlights the applicability of miR-365 as vital therapeutic target against this fatal malignancy.

To compare the surgical outcomes of modified vertical rectus belly transposition (mVRBT) and medial rectus recession (MRc) versus augmented superior rectus transposition (aSRT) and MRc in Chinese patients with chronic abducens nerve palsy.

The medical records of patients with chronic abducens nerve palsy who underwent mVRBT/MRc or aSRT/MRc were retrospectively reviewed. Pre- and postoperative deviation in primary position, pre- and postoperative abduction limitation, and complications were recorded. Follow-up was at least 6months.

A total of 26 patients (mean age, 37.9±19.6years; 16 males [62%]) were included. Fourteen patients underwent mVRBT/MRc (mVRBT group) and 12 underwent aSRT/MRc (aSRT group). Both groups had similar amounts of recession (t=0.27; P=0.79). After surgery, statistically significant changes of abduction limitation and esotropia were observed (both P<0.05). However, the difference in abduction improvement between groups was not statistically significant (mVRBT vs aSRT, 2.3±0.91 vs 2.3±0.97; t=0.10, P=0.92). Of the 19 patients who underwent unilateral surgery, preoperative esotropia was similar in both groups (t=1.3; P=0.21), but more esotropia was corrected in the mVRBT group than in the aSRT group (mVRBT vs aSRT, 57.8

±14.3

vs 44.6

±9.8

 ; t=2.1; P=0.047). There was no symptomatic vertical or torsional deviation.

In our patient cohort, mVRBT/MRc showed a better effect in correcting esotropia and a similar effect in improving abduction limitation compared with aSRT/MRc.

In our patient cohort, mVRBT/MRc showed a better effect in correcting esotropia and a similar effect in improving abduction limitation compared with aSRT/MRc.

To quantitatively compare retinal vascular characteristics over time in eyes eventually treated versus not treated for retinopathy of prematurity (ROP), using ROPtool analysis of narrow-field retinal images.

This longitudinal study used prospectively collected narrow-field retinal images of infants screened for ROP, prior to treatment, if needed. Images were analyzed using a methodology that combines quadrant-level measures from several images of the same eye. For the longitudinal analysis, one examination per postmenstrual age (PMA) was included per eye. We compared the following ROPtool indices and their change per week between eyes eventually treated versus not treated for ROP tortuosity index (TI), dilation index (DI), sum of adjusted indices (SAI), and tortuosity-weighted plus (TWP). Analysis was performed on three levels eye (mean value/eye), quadrant (highest quadrant value/eye), and blood vessel (highest blood vessel value/eye).

Of 832 examinations (99 infants), 745 images (89.5%) had 3-4 quadrants analyzable by ROPtool. On the eye level, ROPtool indices differed between eyes eventually treated versus not treated at PMA of 33-35 and 37weeks for TI, SAI, and TWP, and at PMA of 33-34 and 37weeks for DI (P≤0.0014), and change per week differed between eyes eventually treated versus not treated only for SAI at PMA of 32weeks (P<0.001).

Quantitative analysis of retinal vascular characteristics using ROPtool can help predict eventual need for treatment for ROP as early as 32weeks PMA. see more ROPtool index values were more useful than change in these indices to predict eyes that would eventually need treatment for ROP.

Quantitative analysis of retinal vascular characteristics using ROPtool can help predict eventual need for treatment for ROP as early as 32 weeks PMA. ROPtool index values were more useful than change in these indices to predict eyes that would eventually need treatment for ROP.

To analyze outcomes in a large cohort of spectacle-aversive children with high myopia who were treated by implantation of the Ophtec-Artisan or Visian phakic intraocular lens (pIOL).

Outcome data were collated retrospectively in 78 children (115 eyes) implanted with the Ophtec-Artisan iris-enclaved anterior chamber pIOL and 91 children (154 eyes) implanted with the Visian ICL (intraocular collamer lens) sulcus pIOL. All children had difficulties with spectacle or contact lens wear. Mean age at surgery was 9.9years; mean follow-up was 3.9years (range, 0.6-14.1years).

A total of 248 of 269 eyes (92%) were corrected to within ± 0.5 D of their target value. Spherical correction averaged 12.3±1.0 D. Refractive spherical regression was -0.04 D/year at last follow-up. Uncorrected distance visual acuity improved from an average logMAR 1.8 to 0.4; corrected distance visual acuity improved an average 0.3 logMAR. Of the treated children, 68% had a gain in binocular fusion. Neurobehavioral and/or visuomotor comorbidities were present in 87% of children.

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