Search

A straightforward approach to macrocyclic structures containing deoxysugar subunits was developed through the functionalization of a bishemiketal. The choice of the length and the �nature of the linkers can provide macrocycles with diverse rigidities and polarities. [ABSTRACT FROM AUTHOR]

Generalization allows previous experience to adaptively guide behavior when conditions change. The infralimbic (IL) subregion of the ventral medial prefrontal cortex plays a known role in generalization processes, although mechanisms remain unclear. A basic physical unit of memory storage and expression in the brain are sparse, distributed groups of neurons known as ensembles (i.e., the engram). Here, we set out to determine whether neuronal ensembles established in the IL during learning contribute to generalized responses. Generalization was tested in male and female mice by presenting a novel, ambiguous, tone generalization stimulus following Pavlovian defensive (fear) conditioning. The first experiment was designed to test a role for IL in generalization using chemogenetic manipulations. Results show IL regulates defensive behavior in response to ambiguous stimuli. IL silencing led to a switch in defensive state, from vigilant scanning to generalized freezing, while IL stimulation reduced freezing in favor of scanning. Leveraging activity-dependent "tagging" technology (ArcCreER T2 × eYFP system), a neuronal ensemble, preferentially located in IL Layer 2/3, was associated with the generalization stimulus. Remarkably, in the identical discrete location, fewer reactivated neurons were associated with the generalization stimulus at the remote timepoint (30 days) following learning. When an IL neuronal ensemble established during learning was selectively chemogenetically silenced, generalization increased. Conversely, IL neuronal ensemble stimulation reduced generalization. Overall, these data identify a crucial role for IL in suppressing generalized responses. Further, an IL neuronal ensemble, formed during learning, functions to later attenuate the expression of generalization in the presence of ambiguous threat stimuli., Competing Interests: The authors declare no competing financial interests

Aims: Aortic valve calcification (AVC) of surgical valve bioprostheses (BPs) has been poorly explored. We aimed to evaluate in vivo and ex vivo BP AVCs and its prognosis value., Methods and Results: Between 2011 and 2019, AVC was assessed using in vivo computed tomography (CT) in 361 patients who had undergone surgical valve replacement 6.4 ± 4.3 years earlier. Ex vivo CT scans were performed for 37 explanted BPs. The in vivo CT scans were interpretable for 342 patients (19 patients [5.2%] were excluded). These patients were 77.2 ± 9.1 years old, and 64.3% were male. Mean in vivo AVC was 307 ± 500 Agatston units (AU). The AVC was 562 ± 570 AU for the 183 (53.5%) patients with structural valve degeneration (SVD) and 13 ± 43 AU for those without SVD (P < 0.0001). In vivo and ex vivo AVCs were strongly correlated (r = 0.88, P < 0.0001). An in vivo AVC > 100 AU (n = 147, 43%) had a specificity of 96% for diagnosing Stage 2-3 SVD (area under the curve = 0.92). Patients with AVC > 100 AU had a worse outcome compared with those with AVC ≤ 100 AU (n = 195). In multivariable analysis, AVC was a predictor of overall mortality (hazard ratio [HR] and 95% confidence interval = 1.16 [1.04-1.29]; P = 0.006), cardiovascular mortality (HR = 1.22 [1.04-1.43]; P = 0.013), cardiovascular events (HR = 1.28 [1.16-1.41]; P < 0.0001), and re-intervention (HR = 1.15 [1.06-1.25]; P < 0.0001). After adjustment for Stage 2-3 SVD diagnosis, AVC remained a predictor of overall mortality (HR = 1.20 [1.04-1.39]; P = 0.015) and cardiovascular events (HR = 1.25 [1.09-1.43]; P = 0.001)., Conclusion: CT scan is a reliable tool to assess BP leaflet calcification. An AVC > 100 AU is tightly associated with SVD and it is a strong predictor of overall mortality and cardiovascular events., Competing Interests: Conflict of interest: T.L.T. and J.-Christ R. received a basic research grant from Abbott-St Jude company dedicated to a mitral valve prolapse project. The other authors have no disclosure., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Due to the high prevalence and persistence of long COVID, it is important to evaluate the safety and efficacy of pulmonary rehabilitation (PR) for patients who experience long-lasting symptoms more than six months after initial COVID-19 onset. Enrolled patients were admitted for a four-week in-patient-PR due to long COVID symptoms (n = 47). The safety of PR was confirmed by the absence of adverse events. Symptom-related outcomes were evaluated pre- and post-PR with significant score changes for: 6 min walking distance (61 [28 to 103] m), quality of life (mental Short Form-12: 10 [6 to 13], and physical: 9 [6 to 12]), Montreal Cognitive Assessment (1 [0 to 3]), fatigue (MFI-20: -19 [-28 to -8]), dyspnea (DYSPNEA-12: -7 [-9 to -2] and mMRC; -1 [-1 to 0]), Nijmegen questionnaire (-8 [-11 to -5]), anxiety and depression (HADS:-4 [-5 to -2] and -2 [-4 to -1], respectively) and posttraumatic stress disorder checklist scale (-8 [-12 to -4]). At the individual level, the percentage of symptomatic patients for each outcome decreased, with a high response rate, and the number of persistent symptoms per patient was reduced from six at PR initiation to three at the end of the program. Our results show that in-PR is safe and efficient at decreasing long-lasting symptoms experienced by long COVID patients at more than six months after initial disease onset.

Purpose: Evaluate the clinical outcomes of the secondary piggyback add-on IOL implantation in the ciliary sulcus for pseudophakic patients previously implanted with a monofocal IOL, who pursue a spectacle-free option after IOL surgery., Methods: A prospective case series including seven pseudophakic patients who underwent an in-the-bag monofocal IOL implantation. All eyes underwent a piggyback IOL implantation of the new sulcus designed A4 AddOn IOL in the ciliary sulcus as a secondary procedure for pseudophakic patients pursuing a spectacle-free option for near and intermediate distance after IOL surgery., Results: Seven eyes from six patients were included in this study, from which 4 (71.43%) were female, with a mean age of 58.33 ± 3.5 years (range 54-63; 95% CI 54.66, 62.01). The postoperative spherical equivalent at the 3-month visit was -0.10 m ± 0.82. Also, the UDVA was 0.11 ± 0.08 logMAR, the UIVA 0.01 ± 0.03, and the UNVA 0.01 ± 0.03 3 months after their surgical procedure., Conclusions: The A4 AddOn multifocal IOL's secondary piggyback implant is an efficient alternative for monofocal pseudophakic patients seeking presbyopia solutions. This sulcus-designed IOL provides an optimal visual outcome for near and distance vision.

Background: After heart transplantation, calcineurin inhibitors (CNI) (cyclosporin A and tacrolimus) are key immunosuppressive drugs to prevent graft rejection. Whole-blood concentration (C blood )-guided therapeutic drug monitoring (TDM) is systematically performed to improve graft outcomes. However, some patients will still experience graft rejection and/or adverse events despite CNI C blood within the therapeutic range. Other pharmacokinetic parameters, such as the intragraft, or intracellular concentration at the CNI site of action could refine their TDM. Nonetheless, these remain to be explored. The objective of the INTRACAR study was to describe the relationship between whole blood, intragraft, and intracellular CNI concentrations as well as their efficacy in heart transplant recipients (HTR)., Methods: In a cohort of HTR, protocol endomyocardial biopsies (EMB) were collected to assess rejection by anatomopathological analysis. Part of the EMB was used to measure the intragraft concentrations of CNI (C EMB ). C blood and the concentration inside peripheral blood mononuclear cells, (C PBMC ), a cellular fraction enriched with lymphocytes, were also monitored. Concentrations in the 3 matrices were compared between patients with and without biopsy-proven acute rejection (BPAR)., Results: Thirty-four HTR were included, representing nearly 100 pharmacokinetic (PK) samples for each CNI. C blood , C EMB , and C PBMC correlated for both CNI. BPAR was observed in 74 biopsies (39.6%) from 26 patients (76.5%), all except one was of low grade. None of the PK parameters (C blood , C EMB , C PBMC , C EMB/blood , and C PBMC/blood ) was associated with BPAR., Conclusions: In this cohort of well-immunosuppressed patients, no association was observed for any of the PK parameters, including C blood , with the occurrence of BPAR. However, a trend was noticed for the C EMB and C EMB/blood of cyclosporin A. Further studies in higher-risk patients may help optimize the use of C EMB and C PBMC for CNI TDM in HTR., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

This article focuses on the synthesis of polyhydroxyurethane (PHU) materials containing novel phosphorus flame retardants (FR). Four different phosphorus compounds were grafted onto cyclic carbonate: 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO), diethyl phosphite (DEP), diphenyl phosphite (DPP) and dibenzo[d,f][1,3,2]dioxaphosphepine 6-oxide (BPPO). Thus, three novel phosphorus reactive cyclic carbonates which have never been reported so far were synthetized. Phosphorus FR containing PHU materials were characterized by FTIR to evidence the total conversion of the cyclic carbonate. Moreover, the gel contents up to 80% confirmed the formation of the polymer network. Then, the thermal stability and the flame-retardant properties were investigated by thermogravimetric analyses, cone calorimeter and pyrolysis combustion flow calorimeter. The mode of action of phosphorus compounds, depending on the oxidation state, was especially highlighted. Phosphonate (+III) provided better action in a condensed phase than phosphinate thanks to a more efficient char formation. Among phosphonates, differences were observed in terms of char-formation rate and expansion. DEP provided the best flame-retardant properties, with a reduction of 76% of pHRR with 2 wt% of phosphorus in cone calorimeter analysis. Therefore, this article highlighted the different modes of action of phosphorus flame retardants, depending on the oxidation state of phosphorus, in PHU materials.

Because of a narrow therapeutic index and a wide inter- and intra-patient variability, therapeutic drug monitoring of the immunosuppressant drug tacrolimus (TAC) based on whole-blood concentrations (C blood ) is mandatory in solid organ transplant recipients. Using peripheral blood mononuclear cells concentrations (C PBMC ) could improve patient outcomes. The poor correlation between C blood and C PBMC makes hypothesize that drug transporters are implicated in the intracellular accumulation of TAC. The aim of this work was therefore to clinically study: i) the role of genetic variants and ii) the effect of mRNA and protein expression of 4 drug transporters on the TAC C PBMC/blood ratio. In addition, functional in vitro experiments were performed to mechanistically validate the clinical observations. Genetic variants of ABCB1/P-gp and SLC28A3/CNT3 did not influence TAC C PBMC in liver transplant recipients (LTR). ABCC2/MRP2 at the mRNA level; ABCB1/P-gp, SLC28A3/CNT3 and SLC29A1/ENT1 at the protein level; correlated with the C PBMC/blood in kidney and LTR. In vitro results suing transporter-expressing cells confirmed that TAC is substrate of P-gp but not MRP2, whereas experiments remained inconclusive for CNT3 and ENT1. In conclusion, the genetic-transcription-protein-functional approach presented in this work provides new insights in the understanding of TAC transport at the T lymphocyte plasma membrane., Competing Interests: Declaration of competing interest Gwendal Coste's Ph.D. has been partly funded by Astellas Pharma. Florian Lemaitre has been invited to participation in congresses by Chiesi and Sandoz., (Copyright © 2022 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

Polyurethane (PU) foams are very common materials that have found many applications over the years. Their use is constantly improving due to their unique physical properties and easy blowing which does not require the addition of a blowing agent. Greener routes have been explored in the recent years to replace isocyanates. One of the most promising routes is leading to polyhydroxyurethanes (PHU). However, with PHUs, external blowing agent are usually required to obtain a foam. Thus, the work focuses on PHU foam synthesis using in situ reaction to produce NIPU foam. Hence, the aminolysis of thiocyclic carbonate triggers Pearson reaction between released thiols and cyclic carbonates which serves as a chemical blowing agent., (© 2022 Wiley-VCH GmbH.)

Tacrolimus, the keystone immunosuppressive drug administered after solid organ transplantation, presents a narrow therapeutic index and wide inter- and intra-patient pharmacokinetic variability (IPV). The latter has been fairly studied in kidney transplantation, where it could impact outcomes. However, literature about other transplanted organ recipients remains inconclusive. This review aimed at summarizing the evidence about the IPV of tacrolimus concentrations outside of the scope of kidney transplantation. First, factors influencing IPV will be presented. Then, the potential of IPV as a biomarker predictive of graft outcomes will be discussed in liver, heart, lung and pancreas transplantation. Lastly, strategies to reduce IPV will be reviewed, with the ultimate objective being ready-to-implement solutions in clinical practice by transplantation professionals.

The aim of our investigation was to examine the possible correlations between optical aberrations, angle kappa, angle alpha, and visual outcomes following cataract surgery. In total, 56 eyes of 28 patients were implanted with the Liberty 677MY trifocal intraocular lens (IOL). Pre- and postoperative higher-order aberrations, coma, astigmatism, angle alpha, and angle kappa were registered, along with uncorrected and corrected visual acuities at multiple distances. Visual acuity and contrast sensitivity defocus curves were plotted, and the areas under the curve were calculated 1 and 3 months postoperatively. Excellent visual outcomes were found at all distances. Patients reported low levels of dysphotopsia, and 96.4% of patients achieved complete spectacle independence. While angle kappa significantly decreased during cataract surgery ( p = 0.0007), angle alpha remained unchanged ( p = 0.5158). Angle alpha correlated with postoperative HOAs and had a negative impact on near vision ( p = 0.0543). Preoperative corneal HOA and coma had a strong adverse effect on future intermediate and near vision. Residual astigmatism significantly affected postoperative intermediate vision ( p = 0.0091). Our results suggest that angle kappa is not an optimal predictive factor for future visual outcomes, while angle alpha and the preoperative screening of optical aberrations might help patient selection prior to multifocal IOL implantation.

Purpose: To analyze the association between angle α and ocular biometry in the general population at a third-level ophthalmology hospital., Setting: Anterior Segment Surgery Department, Asociación para Evitar la Ceguera en México I.A.P., Mexico City, Mexico., Design: Prospective, cross-sectional study., Methods: Healthy subjects who attended the hospital for a comprehensive ophthalmological evaluation were examined, and general data were collected. A complete ophthalmological assessment and biomicroscopy evaluation were performed and biometry and clinical data were obtained, including visual acuity, axial length (AL), keratometry (K), white-to-white (WTW) measurement. An OPD-Scan III analyzer was used to assess both the angle α distance and biometry parameters., Results: 74 eyes from the same number of patients were included; 43 (58.10%) were women. A statistically significant inverse correlation was found between the angle α and the AL (r = -0.585; P < .0001) and between the WTW distance and the mean K (r = 0.557; P < .0001). A significant correlation was found between the mean K and the angle α (r = 0.271; P = .019). A significant inverse correlation was observed regarding the WTW distance and angle α (r = -0.359; P = .001). By contrast, a direct correlation was evidenced between the WTW and the AL (r = 0.385; P = .0007)., Conclusions: There was a significant inverse correlation between the AL and the angle α magnitude. Hyperopic patients demonstrated significantly higher angle α values when compared with those of myopic patients. In addition, hyperopic eyes with steeper mean K and lesser WTW distance were associated with an increased angle α., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of ASCRS and ESCRS.)

Numerous genes are overexpressed in the radioresistant bacterium Deinococcus radiodurans after exposure to radiation or prolonged desiccation. It was shown that the DdrO and IrrE proteins play a major role in regulating the expression of approximately twenty genes. The transcriptional repressor DdrO blocks the expression of these genes under normal growth conditions. After exposure to genotoxic agents, the IrrE metalloprotease cleaves DdrO and relieves gene repression. At present, many questions remain, such as the number of genes regulated by DdrO. Here, we present the first ChIP-seq analysis performed at the genome level in Deinococcus species coupled with RNA-seq, which was achieved in the presence or not of DdrO. We also resequenced our laboratory stock strain of D. radiodurans R1 ATCC 13939 to obtain an accurate reference for read alignments and gene expression quantifications. We highlighted genes that are directly under the control of this transcriptional repressor and showed that the DdrO regulon in D. radiodurans includes numerous other genes than those previously described, including DNA and RNA metabolism proteins. These results thus pave the way to better understand the radioresistance pathways encoded by this bacterium and to compare the stress-induced responses mediated by this pair of proteins in diverse bacteria.

Here, we report the in vitro and in vivo characterization of the DdrD protein from the extraordinary stress-resistant bacterium, D. radiodurans. DdrD is one of the most highly induced proteins following cellular irradiation or desiccation. We confirm that DdrD belongs to the Radiation Desiccation Response (RDR) regulon protein family whose expression is regulated by the IrrE/DdrO proteins after DNA damage. We show that DdrD is a DNA binding protein that binds to single-stranded DNA In vitro, but not to duplex DNA unless it has a 5' single-stranded extension. In vivo, we observed no significant effect of the absence of DdrD on the survival of D. radiodurans cells after exposure to γ-rays or UV irradiation in different genetic contexts. However, genome reassembly is affected in a ∆ddrD mutant when cells recover from irradiation in the absence of nutrients. Thus, DdrD likely contributes to genome reconstitution after irradiation, but only under starvation conditions. Lastly, we show that the absence of the DdrD protein partially restores the frequency of plasmid transformation of a ∆ddrB mutant, suggesting that DdrD could also be involved in biological processes other than the response to DNA damage.

Measuring cyclosporine A (CsA), an immunosuppressive drug used to prevent heart transplant rejection, concentrations in myocardial biopsies might be more informative than its measurement in whole blood. Therefore, a fast, accurate and reproductive method to determine CsA concentration in this complex matrix is needed. We report the validation of a liquid chromatography tandem mass spectrometry method to measure CsA concentration in heart parenchyma, applicable to everyday practice. The method was found to be precise, accurate, reproducible, specific of CsA, and without any matrix effect or carry-over. The lower limit of quantification was 50 pg of CsA in myocardium. The method was linear up to 2000 pg of CsA in myocardium. Samples were found stable for one year at - 80 °C. At last, 40 drugs which could be prescribed to heart transplant recipients were tested with the method and showed no interference with CsA signal. The method was suitable to quantify CsA in endomyocardial biopsies from heart transplanted patients. This method allows designing clinical studies aiming at exploring the relationship between CsA intra-graft concentrations and outcome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Horizontal gene transfer is a major driver of bacterial evolution and adaptation to environmental stresses, occurring notably via transformation of naturally competent organisms. The Deinococcus radiodurans bacterium, characterized by its extreme radioresistance, is also naturally competent. Here, we investigated the role of D. radiodurans players involved in different steps of natural transformation. First, we identified the factors (PilQ, PilD, type IV pilins, PilB, PilT, ComEC-ComEA, and ComF) involved in DNA uptake and DNA translocation across the external and cytoplasmic membranes and showed that the DNA-uptake machinery is similar to that described in the Gram negative bacterium Vibrio cholerae . Then, we studied the involvement of recombination and DNA repair proteins, RecA, RecF, RecO, DprA, and DdrB into the DNA processing steps of D. radiodurans transformation by plasmid and genomic DNA. The transformation frequency of the cells devoid of DprA, a highly conserved protein among competent species, strongly decreased but was not completely abolished whereas it was completely abolished in Δ dprA Δ recF , Δ dprA Δ recO , and Δ dprA Δ ddrB double mutants. We propose that RecF and RecO, belonging to the recombination mediator complex, and DdrB, a specific deinococcal DNA binding protein, can replace a function played by DprA, or alternatively, act at a different step of recombination with DprA. We also demonstrated that a Δ dprA mutant is as resistant as wild type to various doses of γ-irradiation, suggesting that DprA, and potentially transformation, do not play a major role in D. radiodurans radioresistance., (Copyright © 2020 Ithurbide, Coste, Lisboa, Eugénie, Bentchikou, Bouthier de la Tour, Liger, Confalonieri, Sommer, Quevillon-Cheruel and Servant.)

Background: Group-based models of Office-Based Opioid Treatment with buprenorphine-naloxone (B/N) are increasingly being implemented in clinical practice to increase access to care and provide additional therapeutic benefits. While previous studies reported these Group-Based Opioid Treatment (GBOT) models are feasible for providers and acceptable to patients, there has been no literature to help providers with the more practical aspects of how to create and maintain GBOT in different outpatient settings. Case series: We present 4 cases of GBOT implementation across a large academic health care system, highlighting various potential approaches for providers who seek to implement GBOT and demonstrate "success" based on feasibility and sustainability of these models. For each case, we describe the pros and cons and detail the personnel and resources involved, patient mix and group format, workflow logistics, monitoring and management, and sustainability components. Discussion: The implementation details illustrate that there is no one-size-fits-all approach, although feasibility is commonly supported by a team-based, patient-centered medical home. This approach includes the capacity for referral to higher levels of mental health and addiction support services and is bolstered by ongoing provider communication and shared resources across the health system. Future research identifying the core and malleable components to implementation, their evidence base, and how they might be influenced by site-specific resources, culture, and other contextual factors can help providers better understand how to implement a GBOT model in their unique clinical environment.

Prospective, randomized, comparative, and controlled study to estimate the association between angle κ distance and higher-order aberrations (HOAs) with postoperative visual acuity after presbyopia-correcting IOL implantation. Forty-three eyes from 43 patients were included and randomly assigned in two groups for either AT LISA tri 839MP or Acrysof IQ PanOptix IOL implantation. The OPD-Scan III analyzer was utilized to assess the angle κ distance and higher-order aberration (HOAs). Twenty-three eyes were in the Acrysof IQ PanOptix group and 20 patients in the AT LISA tri 839MP group. The uncorrected distance visual acuity (UDVA) for the PanOptix group was 0.092 ± 0.10, whereas for AT LISA tri was 0.050 ± 0.06 ( P =0.229). The uncorrected intermediate visual acuity (UIVA) for the PanOptix group was 0.173 ± 0.18, whereas for AT LISA tri, it was 0.182 ± 0.11 ( P =0.669). Uncorrected near visual acuity (UNVA) was 0.068 ± 0.04 and 0.085 ± 0.07, respectively ( P =0.221). Also, correlation coefficient between HOAs and the Strehl ratio for each group were -0.768 ( P < 0.0001) and -0.863 ( P =0.0001). Patients implanted with both trifocal IOLs showed excellent postoperative visual performance at all distances at the six-month follow-up visit. No association was found between angle κ distance and postoperative visual acuity regardless of the angle κ magnitude or the two trifocal IOLs inner optical diameter. Also, internal aberrations demonstrated a significant inverse correlation with the Strehl ratio for both trifocal IOLs., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2019 Cecilio Velasco-Barona et al.)

Understanding the environmental profile of a product computed from the Life Cycle Assessment (LCA) framework is sometimes challenging due to the high number of environmental indicators involved. The objective here, in guiding interpretation of LCA results, is to highlight the importance of each impact category for each product alternative studied. For a given product, the proposed methodology identifies the impact categories that are worth focusing on, relatively to a whole set of products from the same cumulated database. The approach extends the analysis of Representativeness Indices (RI) developed by Esnouf et al. (2018). It proposes a new operational tool for calculating RIs at the level of impact categories for a Life Cycle Inventory (LCI) result. Impact categories and LCI results are defined as vectors within a standardized vector space and a procedure is proposed to treat issues coming from the correlation of impact category vectors belonging to the same Life Cycle Impact Assessment (LCIA) method. From the cumulated ecoinvent database, LCI results of the Chinese and the German electricity mixes illustrate the method. Relevant impact categories of the EU-standardized ILCD method are then identified. RI results from all products of a cumulated LCI database were therefore analysed to assess the main tendencies of the impact categories of the ILCD method. This operational approach can then significantly contribute to the interpretation of the LCA results by pointing to the specificities of the inventories analysed and for identifying the main representative impact categories., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The D NA d amage r esponse ddrI gene encodes a transcription regulator belonging to the cAMP receptor protein (CRP) family. Cells devoid of the DdrI protein exhibit a pleiotropic phenotype, including growth defects and sensitivity to DNA-damaging agents and to oxidative stress. Here, we show that the absence of the DdrI protein also confers sensitivity to heat shock treatment, and several genes involved in heat shock response were shown to be upregulated in a DdrI-dependent manner. Interestingly, expression of the Escherichia coli CRP partially compensates for the absence of the DdrI protein. Microscopic observations of Δ ddrI mutant cells revealed an increased proportion of two-tetrad and anucleated cells in the population compared to the wild-type strain, indicating that DdrI is crucial for the completion of cell division and/or chromosome segregation. We show that DdrI is also involved in the megaplasmid MP1 stability and in efficient plasmid transformation by facilitating the maintenance of the incoming plasmid in the cell. The in silico prediction of putative DdrI binding sites in the D. radiodurans genome suggests that hundreds of genes, belonging to several functional groups, may be regulated by DdrI. In addition, the DdrI protein absolutely requires cAMP for in vitro binding to specific target sequences, and it acts as a dimer. All these data underline the major role of DdrI in D. radiodurans physiology under normal and stress conditions by regulating, both directly and indirectly, a cohort of genes involved in various cellular processes, including central metabolism and specific responses to diverse harmful environments. IMPORTANCE Deinococcus radiodurans has been extensively studied to elucidate the molecular mechanisms responsible for its exceptional ability to withstand lethal effects of various DNA-damaging agents. A complex network, including efficient DNA repair, protein protection against oxidation, and diverse metabolic pathways, plays a crucial role for its radioresistance. The regulatory networks orchestrating these various pathways are still missing. Our data provide new insights into the crucial contribution of the transcription factor DdrI for the D. radiodurans ability to withstand harmful conditions, including UV radiation, mitomycin C treatment, heat shock, and oxidative stress. Finally, we highlight that DdrI is also required for accurate cell division, for maintenance of plasmid replicons, and for central metabolism processes responsible for the overall cell physiology., (Copyright © 2018 American Society for Microbiology.)

Purpose: To compare the biometric measurements obtained from the Verion Image-Guided System to those obtained by auto-refracto-keratometer in normal eyes., Methods: This is a prospective, observational, comparative study conducted at the Asociación para Evitar la Ceguera en México I.A.P., Mexico. Three sets of keratometry measurements were obtained using the image-guided system to assess the coefficient of variation, the within-subject standard deviation and intraclass correlation coefficient (ICC). A paired Student t test was used to assess statistical significance between the Verion and the auto-refracto-keratometer. A Pearson's correlation coefficient (r) was obtained for all measurements, and the level of agreement was verified using Bland-Altman plots., Results: The right eyes of 73 patients were evaluated by each platform. The Verion coefficient of variation was 0.3% for the flat and steep keratometry, with the ICC being greater than 0.9 for all parameters measured. Paired t test showed statistically significant differences between groups (P = 0.0001). A good correlation was evidenced for keratometry values between platforms (r = 0.903, P = 0.0001 for K1, and r = 0.890, P = 0.0001). Bland-Altman plots showed a wide data spread for all variables., Conclusion: The image-guided system provided highly repeatable corneal power and keratometry measurements. However, significant differences were evidenced between the two platforms, and although values were highly correlated, they showed a wide data spread for all analysed variables; therefore, their interchangeable use for biometry assessment is not advisable.

Pediatric cataract surgery poses a significant challenge for the cataract surgeon, in part because an elastic anterior capsule can make capsulorhexis difficult. With the use of femtosecond laser-assisted cataract surgery (FLACS), however, the continuous curvilinear capsulorhexis can be made with predictable size, circular shape, centration, and accuracy. In addition, topical anesthesia can be used for the FLACS docking procedure in cooperative children above 6 years of age, using transparent adhesive polyurethane film segments., (Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

The bacterium Deinococcus radiodurans is one of the most radioresistant organisms known. It is able to reconstruct a functional genome from hundreds of radiation-induced chromosomal fragments. Our work aims to highlight the genes involved in recombination between 438 bp direct repeats separated by intervening sequences of various lengths ranging from 1,479 bp to 10,500 bp to restore a functional tetA gene in the presence or absence of radiation-induced DNA double strand breaks. The frequency of spontaneous deletion events between the chromosomal direct repeats were the same in recA+ and in ΔrecA, ΔrecF, and ΔrecO bacteria, whereas recombination between chromosomal and plasmid DNA was shown to be strictly dependent on the RecA and RecF proteins. The presence of mutations in one of the repeated sequence reduced, in a MutS-dependent manner, the frequency of the deletion events. The distance between the repeats did not influence the frequencies of deletion events in recA+ as well in ΔrecA bacteria. The absence of the UvrD protein stimulated the recombination between the direct repeats whereas the absence of the DdrB protein, previously shown to be involved in DNA double strand break repair through a single strand annealing (SSA) pathway, strongly reduces the frequency of RecA- (and RecO-) independent deletions events. The absence of the DdrB protein also increased the lethal sectoring of cells devoid of RecA or RecO protein. γ-irradiation of recA+ cells increased about 10-fold the frequencies of the deletion events, but at a lesser extend in cells devoid of the DdrB protein. Altogether, our results suggest a major role of single strand annealing in DNA repeat deletion events in bacteria devoid of the RecA protein, and also in recA+ bacteria exposed to ionizing radiation.

The purpose of this study is to determine baseline vitreous humor temperature during a combined phacoemulsification and pars plana vitrectomy (PPV) procedure; to determine what is the temperature variation during phacoemulsification; and to compare vitreous temperature to sublingual temperature. The methods used are prospective, interventional and comparative study. Patients with a diagnosis of cataract and vitreous hemorrhage, programed for a combined procedure of phacoemulsification and PPV, were included. Patients were excluded if posterior capsular rupture existed during the anterior segment procedure. A thermoprobe was inserted through a PPV trocar. Measurement of the vitreous temperature was obtained at baseline and throughout phacoemulsification, at the end of every surgical step, and every 5 min. Sublingual temperature was measured with the same probe at the end of the surgery. Room temperature was registered. Seventeen eyes of 17 patients were included. Mean sublingual temperature was 36.5 °C (standard deviation [σ] 0.26 °C). Mean total vitreous temperature was 31.47 °C (σ 2.1 °C). Mean baseline vitreous temperature was 33.04 °C (σ 0.99 °C). Comparison of sublingual temperature with baseline vitreous temperature resulted in a significant difference (t test P < 0.000. 95 % confidence interval 2.93-3.98). Temperature measured by surgical step and surgical time presented a significant decrease in temperature from baseline (Kruskal-Wallis P < 0.000, P = 0.003, respectively). Vitreous humor is significantly hypothermic when compared to sublingual temperature. Vitreous temperature decreases significantly during phacoemulsification.

Here, we have developed an extremely efficient in vivo Tn5-based mutagenesis procedure to construct a Deinococcus radiodurans insertion mutant library subsequently screened for sensitivity to genotoxic agents such as γ and UV radiations or mitomycin C. The genes inactivated in radiosensitive mutants belong to various functional categories, including DNA repair functions, stress responses, signal transduction, membrane transport, several metabolic pathways, and genes of unknown function. Interestingly, preliminary characterization of previously undescribed radiosensitive mutants suggests the contribution of cyclic di-AMP signaling in the recovery of D. radiodurans cells from genotoxic stresses, probably by modulating several pathways involved in the overall cell response. Our analyses also point out a new transcriptional regulator belonging to the GntR family, encoded by DR0265, and a predicted RNase belonging to the newly described Y family, both contributing to the extreme radioresistance of D. radiodurans. Altogether, this work has revealed new cell responses involved either directly or indirectly in repair of various cell damage and confirmed that D. radiodurans extreme radiation resistance is determined by a multiplicity of pathways acting as a complex network.

Purpose: To examine the stability and efficacy of high-cylinder power AcrySof toric intraocular lenses (IOLs), models SN60T6, SN60T7, SN60T8, and SN60T9 (Alcon Laboratories Inc)., Methods: Eligible eyes had cataract and symmetric corneal astigmatism > 2.25 diopters (D). Outcomes included monocular uncorrected distance visual acuity (UDVA), manifest refraction, and assessment of IOL axis., Results: Nineteen eyes from 14 patients had preoperative corneal astigmatism of 4.00 ± 1.10 D. Postoperatively, residual refractive cylinder was 0.55 ± 0.60 D at 3 months. Uncorrected distance visual acuity was 1.3 ± 0.5 logMAR preoperatively and improved to 0.11 ± 0.09 logMAR 3 months postoperatively (P<.0001). All IOLs were stable within 5°., Conclusions: The IOLs were stable and effective in correcting high amounts of preexisting astigmatism at the time of cataract surgery., (Copyright 2012, SLACK Incorporated.)