uiring C3F8 gas. At the 6-week IOP check, the patient was noted to have early central opacification of the IOL (). IOL opacification continued to progress and the vision declined to CDVA of 20/200 by 3 months postoperatively ().(Figure is included in full-text article.)(Figure is included in full-text article.)What is the next step in management for this patient given the comorbidities of an opacified IOL, advanced glaucoma, anticoagulation status, and diffuse 360 degrees transillumination iris defects?

To assess whether the combined implantation of a monofocal IOL and an artificial iris had an effect on the IOL’s optical performance.

David J. Apple International Laboratory for Ocular Pathology, Heidelberg, Germany.

In vitro laboratory study.

IOL optical quality was assessed using an OptiSpheric IOL Pro II to measure the IOL’s modulation transfer function (MTF) at 3.0 mm pupil size and spatial frequency of 100 lp/mm. Three ASPIRA-aAY IOLs with different base powers, 10.0 diopter (D) (IOL A), 20.0 D (IOL B), and 30.0 D (IOL C) were measured before and after suturing the IOL to an ArtificialIris (AI). The degree of IOL decentration about the center of the AI was also evaluated.

The mean MTF values prior to suturing were 0.57, 0.65, and 0.63 for IOLs A, B, and C, respectively. After suturing to the AI, the mean MTF values were 0.52, 0.54, and 0.55 for IOLs A, B, and C, respectively. The decentration values in vertical direction were 0.20 mm, 0.00 mm, and 0.02 mm for IOLs A, B, and C, respectively. In horizontal direction, the decentration values were 0.42 mm, 0.10 mm, and 0.03 mm for IOLs A, B, and C, respectively.

The MTF decreased slightly in all 3 IOLs after they were sutured to the AI. The small differences, however, should be clinically irrelevant. This laboratory assessment showed that suturing of the IOL to the AI can be performed in a reliable and reproducible manner without deteriorating optical quality.

The MTF decreased slightly in all 3 IOLs after they were sutured to the AI. The small differences, however, should be clinically irrelevant. This laboratory assessment showed that suturing of the IOL to the AI can be performed in a reliable and reproducible manner without deteriorating optical quality.

To compare vergence, artificial intelligence, and combined intraocular lens (IOL) calculation formulas using a new swept-source optical coherence tomographer (SS-OCT) and to analyze their performance based on manifest and estimated refractive outcomes of cataract surgery.

Department of Ophthalmology, University of Pécs Medical School, Pécs, Hungary.

Retrospective data analysis.

Optical biometry readings of patients who underwent uneventful cataract removal and implantation of a monofocal acrylic IOL were used to predict IOL power with Barrett Universal II (BUII), Haigis, Hoffer Q, Holladay 1, Radial Basis Function (RBF) 2.0, Kane, Ladas Super Formula, and SRK/T. All the implanted IOLs were calculated by using the Haigis formula. The arithmetic prediction error and median and mean absolute refractive errors for all formulas were computed. The percentage of eyes within ±0.25 diopters (D), ±0.50 D, and ±1.0 D of prediction error was calculated.

A total of 95 eyes of 95 patients with a mean age of 68.80 ± 7.57 years were included. There was a statistically significant difference in absolute prediction error across the 8 IOL calculation formulas (P < .0001). Haigis showed the lowest mean absolute error, and it differed significantly from the BUII, Hoffer Q, Holladay 1, Ladas, RBF 2.0, and SRK/T formulas (P < .05). In terms of eyes within ±0.25 D, ±0.50 D, and ±1.0 D of prediction error, the Haigis formula showed the overall best performance.

The results indicated that a recently developed SS-OCT provided accurate ocular biometry measurements before cataract surgery, and the Haigis formula incorporated in its software enabled precise calculation of IOL refractive power.

The results indicated that a recently developed SS-OCT provided accurate ocular biometry measurements before cataract surgery, and the Haigis formula incorporated in its software enabled precise calculation of IOL refractive power.

To investigate interleukin (IL)-1β, IL-6, and total prostaglandin (PG) levels in the anterior chamber in patients undergoing low pulse energy femtosecond laser-assisted cataract surgery.

Forty patients undergoing immediate sequential cataract surgery received randomized low-energy femtosecond laser pretreatment in 1 eye and conventional phacoemulsification in the other. Aqueous humor was collected precisely 5 minutes after femtosecond laser pretreatment and before conventional phacoemulsification from all 80 eyes. IL-1β, IL-6, and total PG (including PGE1, PGE2; PGF1a, PGF2a) levels were analyzed using enzyme-linked immunoassay kits. One drop of ketorolac 0.5% was administered 30 minutes preoperatively.

Mean concentrations of IL-1β, IL-6, and total PG were 0.87, 0.67, and 32.19 pg/mL in the femto group compared with 0.10 (P = .36), 0.78 (P = .79), and 19.66 pg/mL (P < .05) in the nonfemto group. Levels of IL-1β and IL-6 were not statistically significantly different when compared between groups. Thereaction was due to the lower pulse energy concept applied by the femtosecond laser.Gaps in the translation of research findings to clinical management have been recognized for decades. They exist for the diagnosis as well as the management of cancer. The international standards for cancer diagnosis are contained within the World Health Organization (WHO) Classification of Tumours, published by the International Agency for Research on Cancer (IARC) and known worldwide as the WHO Blue Books. In addition to their relevance to individual patients, these volumes provide a valuable contribution to cancer research and surveillance, fulfilling an important role in scientific evidence synthesis and international standard setting. However, the multidimensional nature of cancer classification, the way in which the WHO Classification of Tumours is constructed, and the scientific information overload in the field pose important challenges for the translation of research findings to tumour classification and hence cancer diagnosis. To help address these challenges, we have established the International Collaboration for Cancer Classification and Research (IC3 R) to provide a forum for the coordination of efforts in evidence generation, standard setting and best practice recommendations in the field of tumour classification. The first IC3 R meeting, held in Lyon, France, in February 2019, gathered representatives of major institutions involved in tumour classification and related fields to identify and discuss translational challenges in data comparability, standard setting, quality management, evidence evaluation and copyright, as well as to develop a collaborative plan for addressing these challenges.Recent studies have evaluated the possible efficacy of mindfulness-based interventions (MBIs) for social anxiety disorder (SAD). However, few trials have compared MBIs with a first-line treatment. This study evaluated the relative efficacy of an MBI adapted for SAD (MBI-SAD) to cognitive behaviour group therapy (CBGT) for SAD. Participants were randomized to 12 weekly group sessions of the MBI-SAD (n = 52) or CBGT (n = 45). Results revealed that CBGT fared better than the MBI-SAD in reducing clinician- and self-rated social anxiety severity. The difference between the MBI-SAD and CBGT exceeded the prespecified noninferiority margin for our primary outcome the Liebowitz Social Anxiety Scale, but findings are inconclusive as the width of the confidence interval extended in both directions surrounding the noninferiority margin. The MBI-SAD compared favourably with CBGT in improving other indices of well-being (depression, self-esteem, satisfaction with life, social adjustment). Contrary to expectation, the MBI-SAD did not produce greater changes in mindfulness and self-compassion than CBGT. Overall, results confirm that CBGT is robust treatment for SAD and should be considered as first-line treatment.Ni-rich LiNi0.8 Co0.15 Al0.05 O2 (NCA) material attracts extensive attention due to its high discharge specific capacity, but its distinct drawbacks of rapid capacity decline and poor cycle performance at elevated temperatures and high voltage during charge/discharge cycling restricts its widespread application. To solve these problems, a multifunctional coating layer composed of a lithium-ion-conductive lithium polyacrylate (LiPAA) inner layer and a cross-linked polymer outer layer from certain organic substances of silane-coupling agent (KH550) and polyacrylic acid (PAA) is successfully designed on the surface of NCA materials, which is favorable for eliminating residual lithium and improving lithium-ion conductivity, surface stability, and hydrophobicity of NCA materials. In addition, the amount of the coating material is also investigated. A series of characterization methods such as XRD, FTIR, SEM, TEM, and X-ray photoelectron spectroscopy are used to analyze the morphologies and structures for materials of pristine and modified NCA. It is revealed that the co-coating layer plays a vital part in reducing the surface residual alkalis and improving the stability of NCA particles; as a result, the modified NCA exhibits a greatly improved rate capability, cycle performance, and low polarization impedance.

What is the central question of this study? MiR-92b-3p was found to be reduced in a rat model of middle cerebral artery occlusion what are the functions of miR-92b-3p in oxygen and glucose deprivation-reperfusion (OGD/R)? What is the main finding and its importance? MiR-92b-3p abated apoptosis, mitochondrial dysfunction and inflammation caused by OGD/R via targeting TRAF3, suggesting that miR-92b-3p may serve as a potential therapeutic target in ischaemic stroke treatment.

Stroke is the most common cause of human neurological disability. MiR-92b-3p has been shown to be decreased in a rat model of middle cerebral artery occlusion, but its effects in cerebral ischaemic insult are unknown. In this study, PC12 cells were exposed to oxygen and glucose deprivation-reperfusion (OGD/R) to establish cerebral ischaemic injury in vitro. Quantitative real time-PCR analysis demonstrated that OGD/R exposure led to down-regulation of miR-92b-3p and increased mRNA and protein levels of tumour necrosis factor receptor-assand inflammatory responses induced by OGD/R by targeting TRAF3.

There has been a concern that blood donations can increase the risk of hematological malignancies. We investigated if blood donations increase the risk of developing hematological malignancies, specifically acute lymphoblastic leukemia, acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia, Hodgkin lymphoma, and myeloma, as well other non-Hodgkin lymphoma.

In total, the study included 1,021,433 Swedish blood donors, with 19.5 million person-years of follow-up. Two sets of analysis were performed. In the first cohort analysis, standardized incidence ratios (SIRs) were calculated, comparing the incidence of the different types of hematological cancers in blood donors to that of the general population. In the second analysis, a nested case-control study was conducted, investigating the association between number of donations and the risk of each type of malignancy.

Apart from a modestly elevated risk of CLL (SIR, 1.07; 95% confidence interval [CI], 1.01-1.15) and a modestly decreased risk of AML (SIR, 0.85; 95% CI, 0.77-0.83), the risk of hematological malignancies did not differ between blood donors and the general population. In the nested case-control study there were no convincing associations between number of prior whole blood donations and site-specific malignancy risk.

There was no convincing evidence of an increased risk in any hematological malignancy when interpreting the results from both series of analyses.

There was no convincing evidence of an increased risk in any hematological malignancy when interpreting the results from both series of analyses.The cystine/glutamate antiporter, system xc- , is essential for the efficient uptake of cystine into cells. Interest in the mechanisms of system xc- function soared with the recognition that system xc- presents the most upstream node of ferroptosis, a recently described form of regulated necrosis relevant for degenerative diseases and cancer. Since targeting system xc- hold the great potential to efficiently combat tumor growth and metastasis of certain tumors, we disrupted the substrate-specific subunit of system xc- , xCT (SLC7A11) in the highly metastatic mouse B16F10 melanoma cell line and assessed the impact on tumor growth and metastasis. Subcutaneous injection of tumor cells into the syngeneic B16F10 mouse melanoma model uncovered a marked decrease in the tumor-forming ability and growth of KO cells compared to control cell lines. Strikingly, the metastatic potential of KO cells was markedly reduced as shown in several in vivo models of experimental and spontaneous metastasis. Accordingly, survival rates of KO tumor-bearing mice were significantly prolonged in contrast to those transplanted with control cells. Analyzing the in vitro ability of KO and control B16F10 cells in terms of endothelial cell adhesion and spheroid formation revealed that xCT expression indeed plays an important role during metastasis. Hence, system xc- emerges to be essential for tumor metastasis in mice, thus qualifying as a highly attractive anticancer drug target, particularly in light of its dispensable role for normal life in mice.Analysis of routine population-based data has previously shown that patterns of surgical treatment for colorectal cancer can vary widely, but there is limited evidence available to determine if such variation is also seen in the use of chemotherapy. This study quantified variation in adjuvant chemotherapy across both England using cancer registry data and in more detail across the representative Yorkshire and Humber regions. Individuals with Stages II and III colorectal cancer who underwent major resection from 2014 to 2015 were identified. Rates of chemotherapy were calculated from the Systemic Anticancer Treatment database using multilevel logistic regression. Additionally, questionnaires addressing different clinical scenarios were sent to regional oncologists to investigate the treatment preferences of clinicians. The national adjusted chemotherapy treatment rate ranged from 2% to 46% (Stage II cancers), 19% to 81% (Stage III cancers), 24% to 75% (patients aged less then 70 years) and 5% to 46% (patients aged ≥70 years). Regionally, the rates of treatment and the proportions of treated patients receiving combination chemotherapy varied by stage (Stage II 4%-26% and 0%-55%, Stage III 48%-71% and 40%-84%) and by age ( less then 70 years 35%-68% and 49%-91%; ≥70 years 15%-39% and 6%-75%). Questionnaire responses showed significant variations in opinions for high-risk Stage II patients with both deficient and proficient mismatch repair tumours and Stage IIIB patients aged ≥70 years. Following a review of the evidence, open discussion in our region has enabled a consensus agreement on an algorithm for colorectal cancer that is intended to reduce variation in practice.Emerging evidence suggests that long non-coding RNA (lncRNA) plays an important role in disease development, particularly in cancers. Recent studies with genome-wide sequencing on cervical squamous cell carcinoma and matched adjacent non-tumour tissues showed that a newly identified lncRNA-lnc_000231 was highly expressed in cervical cancers. However, the underlying mechanism through which it is activated and its role in cervical cancer progression is still unclear. In this study, first, we confirmed that lnc_000231 is up-regulated in cervical cancer cells and tumour tissues. Mechanically, we demonstrated that E6 up-regulates lnc_000231 expression through promoting its promoter region H3K4me3 modification by destabilizing KDM5C. In vitro and in vivo results showed that lnc_000231 promotes cervical cancer cell proliferation and tumour formation by acting as miR-497-5p sponge and maintaining cyclin E1 (CCNE1) expression. Thus, our studies identified a new signalling pathway through which E6 promotes cervical cancer progression. E6 hijacked KDM5C/lnc_000231/miR-497-5p/CCNE1 signalling pathway is a promising target for cervical cancer treatment in the future.Separation selectivity and detection sensitivity of reversed-phase high-performance liquid chromatography with tandem mass spectrometry analyses were compared for formic (0.1%) and formic/heptafluorobutyric (0.1%/0.005%) acid based eluents using a proteomic data set of ∼12 000 paired peptides. The addition of a small amount of hydrophobic heptafluorobutyric acid ion-pairing modifier increased peptide retention by up to 10% acetonitrile depending on peptide charge, size, and hydrophobicity. Retention increase was greatest for peptides that were short, highly charged, and hydrophilic. There was an ∼3.75-fold reduction in MS signal observed across the whole population of peptides following the addition of heptafluorobutyric acid. This resulted in ∼36% and ∼21% reduction of detected proteins and unique peptides for the whole cell lysate digests, respectively. We also confirmed that the separation selectivity of the formic/heptafluorobutyric acid system was very similar to the commonly used conditions of 0.1% trifluoroacetic acid, and developed a new version of the Sequence-Specific Retention calculator model for the formic/heptafluorobutyric acid system showing the same ∼0.98 R2 -value accuracy as the Sequence-Specific Retention calculator formic acid model. In silico simulation of peptide distribution in separation space showed that the addition of 0.005% heptafluorobutyric acid to the 0.1% formic acid system increased potential proteome coverage by ∼11% of detectable species (tryptic peptides ≥ four amino acids).

Obstructive sleep apnea (OSA) and sickle cell disease (SCD) represent two complex disease processes. Current guidelines recommend that children with SCD receive polysomnography (PSG) after presenting with signs or symptoms of sleep-disordered breathing (SDB). Recent studies suggest a disproportionately elevated prevalence of SDB in the population of children with SCD, and traditional risk factors may not be evident within these patients. Further objective testing might be needed to screen all pediatric patients with SCD, even in the absence of overt signs or symptoms of OSA to prevent complications of both conditions.

Prospective cohort study METHODS Institutional review board approval was obtained. An eight-question OSA risk assessment screening questionnaire was presented prospectively to 100 consecutive patients with SCD in the pediatric hematology clinic regardless of complaints of SDB.

Out of 100 patients, 51 were female. The average age, body mass index (BMI), BMI percentile, and I’M SLEEPY score of the entire cohort were 3.97 years, 15.97%, 55.4%, and 1.63%, respectively. Nineteen patients had a positive sleep apnea screening score and were referred for PSG. The average age BMI, BMI percentile, and I’M SLEEPY score for those 19 patients were 3.77%, 16.67%, 65%, and 3.95%, respectively. Ten patients completed PSG, with seven diagnosed with OSA.

This pilot study demonstrates a higher incidence of SDB and OSA in children with SCD relative to the general pediatric population. Although more PSG reports and further testing is needed to determine whether the results hold, preliminary data indicate that children with SCD should at least undergo OSA screening in the office regardless of overt symptoms.

3 Laryngoscope, 2020.

3 Laryngoscope, 2020.Astrocytes provide metabolic support for neurons and modulate their functions by releasing a plethora of neuroactive molecules diffusing to neighboring cells. Here we report that astrocytes also play a role in cortical neurons’ vulnerability to Herpes simplex virus type-1 (HSV-1) infection through the release of extracellular ATP. We found that the interaction of HSV-1 with heparan sulfate proteoglycans expressed on the plasma membrane of astrocytes triggered phospholipase C-mediated IP3 -dependent intracellular Ca2+ transients causing extracellular release of ATP. ATP binds membrane purinergic P2 receptors (P2Rs) of both neurons and astrocytes causing an increase in intracellular Ca2+ concentration that activates the Glycogen Synthase Kinase (GSK)-3β, whose action is necessary for HSV-1 entry/replication in these cells. Indeed, in co-cultures of neurons and astrocytes HSV-1-infected neurons were only found in proximity of infected astrocytes releasing ATP, whereas in the presence of fluorocitrate, an inhibitor of astrocyte metabolism, switching-off the HSV-1-induced ATP release, very few neurons were infected. The addition of exogenous ATP, mimicking that released by astrocytes after HSV-1 challenge, restored the ability of HSV-1 to infect neurons co-cultured with metabolically-inhibited astrocytes. The ATP-activated, P2R-mediated, and GSK-3-dependent molecular pathway underlying HSV-1 infection is likely shared by neurons and astrocytes, given that the blockade of either P2Rs or GSK-3 activation inhibited infection of both cell types. These results add a new layer of information to our understanding of the critical role played by astrocytes in regulating neuronal functions and their response to noxious stimuli including microbial agents via Ca2+ -dependent release of neuroactive molecules.The timing between synaptic inputs has been proposed to play a role in the induction of plastic changes that enable neural circuits to store information. In the case of spike timing-dependent plasticity (STDP), this relates to the interval between a synaptic input and a postsynaptic spike, thus providing a conceptual link to the Hebb learning rule. Experiments have documented STDP in many synapses and brain regions, and computational models have tested its utility in many neural network functions. However, questions remain about whether timing plays a role in plasticity during natural activity, and whether it can function in information storage. The present study used imaging with voltage sensitive dye to investigate the effectiveness of input timing in the plasticity of responses in the CA3 region of hippocampal slices. Plasticity was induced by sequential dual-site stimulation at 10 ms intervals of either synaptic inputs and cell bodies (synaptic-somatic induction) or of two sets of synaptic inputs (synaptif LTP and in the storage of information.High-temperature treatment of γ-Al2 O3 can lead to a series of polymorphic transformations, including the formation of δ-Al2 O3 and θ-Al2 O3 . Quantification of the microstructure in the range where δ- and θ-Al2 O3 are formed represents a formidable challenge, as both phases accommodate a high degree of structural disorder. In this work, we explore the use of an XRD recursive-stacking formalism for the quantification of high-temperature transition aluminas. We formulate the recursive-stacking methodology for modelling of disorder in δ-Al2 O3 and twinning in θ-Al2 O3 and show that explicitly accounting for the disorder is necessary to reliably model the XRD patterns of high-temperature transition alumina. We also use the recursive stacking approach to study phase transformation during high-temperature (1050 °C) treatment. We show that the two different intergrowth modes of δ-Al2 O3 have different transformation characteristics and that a significant portion of δ-Al2 O3 is stabilized with θ-Al2 O3 even after prolonged high-temperature exposures.

What is the central question of this study? β-Adrenergic receptor activation modulates cutaneous vasodilatation and sweating in young adults. In this study, we assessed whether age-related differences in β-adrenergic regulation of these responses exist and whether they differ between men and women. What is the main finding and its importance? We showed that ageing augmented β-adrenergic cutaneous vasodilatation, although the pattern of response differed between men and women. Ageing had no effect on β-adrenergic sweating in men or women. Our findings advance our understanding of age-related changes in the regulation of cutaneous vasodilatation and sweating and provide new directions for research on the significance of enhanced β-adrenergic cutaneous vasodilatation in older adults.

β-Adrenergic receptor agonists, such as isoprenaline, can induce cutaneous vasodilatation and sweating in young adults. Given that cutaneous vasodilatation and sweating responses to whole-body heating and to pharmacological agonat ageing augments β-adrenergic cutaneous vasodilatation differently in men and women, without influencing β-adrenergic sweating.

Maximum fascicle shortening/rotation was significantly decreased in paretic medial gastrocnemius (MG) muscles compared to non-paretic MG muscles. The fascicle gear ratio on both sides decreased as the ankle became dorsiflexed, but the slope of the fascicle gear ratio over ankle joint angle was significantly lower on the paretic side. The side-to-side slope difference was strongly correlated with the relative maximum joint torque and with the relative shear wave speed, suggesting that variable gearing may explain muscle weakness after stroke.

The present study aimed to understand variable fascicle gearing during voluntary isometric contractions of the medial gastrocnemius (MG) muscle in chronic stroke survivors. Using ultrasonography, we characterized fascicle behaviour on both paretic and non-paretic sides during plantarflexion contractions at different intensities and at different ankle joint angles. Shear wave speed was also recorded from the MG muscle belly under passive conditions. Fascicle gear ratioound a significant reduction in both maximum fascicle shortening and maximum fascicle rotation on the paretic side compared to the non-paretic side on our stroke survivor cohort. The fascicle rotation per fascicle shortening on the paretic side was also significantly smaller than on the non-paretic side, especially at plantarflexed positions. Furthermore, the fascicle gear ratio on both sides decreased as the ankle became dorsiflexed, but the change in the fascicle gear ratio was significantly lower on the paretic side. The side-to-side difference in the gear ratio slope was also strongly correlated with the relative maximum joint torque and with the relative shear wave speed, suggesting that variable gearing may explain muscle weakness after stroke. Further studies are needed to investigate how muscular changes after stroke may impede variable gearing and adversely impact muscle performance.

Lung adenocarcinomas present as tight clusters and three-dimensional balls in effusion specimens. Unlike carcinomas of breast and stomach where singly lying malignant cells are seen in effusion samples, lung adenocarcinomas usually show cohesive morphology. This single-cell pattern may also be confused with reactive mesothelial cells. We studied the frequency of pulmonary adenocarcinoma with single-cell pattern cytomorphology in pleural effusion specimens.

All cases reported as either suspicious or positive for malignancy on pleural effusion cytology (PFC) over the past 1 year were retrieved. The clinical details were obtained from requisition forms. Cases with predominant single-cell pattern, clinically suspicious of carcinoma lung were segregated. These were de-stained and immunocytochemistry (ICC) for TTF-1 was performed.

Of 103 cases reported as either suspicious or positive for malignancy on PFC, 29 had a predominant single-cell pattern. Of these, 13 (44.8%) were primary lung carcinoma. The rest were metastasis from ovary (5; 17.2%), breast (2; 6.9%), stomach (2; 6.9%), lymphoma (1; 3.5%), and Ewing’s sarcoma (1; 3.5%). Five (17.2%) were those with unknown primary. All cases of lung carcinoma were positive for TTF-1 ICC.

Single-cell pattern of pulmonary adenocarcinoma is commoner than popularly believed. This pattern may be difficult to differentiate from carcinoma cells of other sites as well as from reactive mesothelial cells. A high degree of suspicion is therefore needed to perform relevant ICC to clinch the correct diagnosis.

Single-cell pattern of pulmonary adenocarcinoma is commoner than popularly believed. This pattern may be difficult to differentiate from carcinoma cells of other sites as well as from reactive mesothelial cells. A high degree of suspicion is therefore needed to perform relevant ICC to clinch the correct diagnosis.Lithium phosphorus oxynitride (LiPON) is an amorphous solid-state lithium ion conductor displaying exemplary cyclability against lithium metal anodes. There is no definitive explanation for this stability due to the limited understanding of the structure of LiPON. Herein, we provide a structural model of RF-sputtered LiPON. Information about the short-range structure results from 1D and 2D solid-state NMR experiments. These results are compared with first principles chemical shielding calculations of Li-P-O/N crystals and ab initio molecular dynamics-generated amorphous LiPON models to unequivocally identify the glassy structure as primarily isolated phosphate monomers with N incorporated in both apical and as bridging sites in phosphate dimers. Structural results suggest LiPON’s stability is a result of its glassy character. Free-standing LiPON films are produced that exhibit a high degree of flexibility, highlighting the unique mechanical properties of glassy materials.

To define methods to measure dysarthria due to stroke and guide physicians in delineating a diagnostic protocol using the best current strategies.

Systematic review.

A search was conducted on PubMed, EMBASE, the Cochrane Library, and Web of Science to identify measurement methods for dysarthria severity in adults after stroke.

Two reviewers independently reviewed articles and came to a consensus about which ones to include. The authors excluded all duplicates, articles involving individuals with aphasia or other speech problems other than dysarthria, and articles unrelated to stroke. Articles were included if diagnostic measures were used to examine the effectiveness of speech rehabilitation in stroke patients.

The search identified 1154 articles with the keywords „stroke” OR „ictus” OR „cerebral vascular accident” AND „dysarthria” OR „Speech and Language Disorders” AND „diagnosis” OR „assessment.” The reviewers analyzed 86 full texts. There were 37 publications that met the criteria and were included in the systematic review. These articles were used to describe the main methods used for measuring the severity of stroke-related dysarthria before and after speech rehabilitation.

Despite the range of diagnostic tools available, robust trials are lacking, and the diagnostic approaches are always different. More research is needed to find the best diagnostic methodologies and delineate a definitive diagnostic protocol.

Despite the range of diagnostic tools available, robust trials are lacking, and the diagnostic approaches are always different. More research is needed to find the best diagnostic methodologies and delineate a definitive diagnostic protocol.Complete surgical resection of pulmonary metastatic disease in patients with osteosarcoma is crucial to long-term survival. Open thoracotomy allows palpation of nodules not identified on imaging but the impact on survival is unknown. The objective of this study was to compare overall survival (OS) and pulmonary disease-free survival (DFS) in children who underwent thoracotomy vs thoracoscopic surgery for pulmonary metastasectomy. A multi-institutional collaborative group retrospectively reviewed 202 pediatric patients with osteosarcoma who underwent pulmonary metastasectomy by thoracotomy (n = 154) or thoracoscopy (n = 48). Results were analyzed by Kaplan-Meier survival estimates and multivariate Cox proportional hazard regression models. With median follow-up of 45 months, 135 (67.5%) patients had a pulmonary relapse and 95 (47%) patients were deceased. Kaplan-Meier analysis showed no significant difference in 5-year pulmonary DFS (25% vs 38%; P = .18) or OS (49% vs 42%, P = .37) between the surgical approaches of thoracotomy and thoracoscopy. In Cox regression analysis controlling for other factors impacting outcome, there was a significantly increased risk of mortality (HR 2.11; P = .027; 95% CI 1.09-4.09) but not pulmonary recurrence (HR 0.96; P = .90; 95% CI 0.52-1.79) with a thoracoscopic approach. However, in the subset analysis limited to patients with oligometastatic disease, thoracoscopy had no increased risk of mortality (HR 1.16; P = .62; 0.64-2.11). In conclusion, patients with metastatic osteosarcoma and limited pulmonary disease burden demonstrate comparable outcomes after thoracotomy and thoracoscopy for metastasectomy. While significant selection bias in these surgical cohorts limits the generalizability of the conclusions, clinical equipoise for a randomized clinical trial in patients with oligometastatic disease is supported.We propose a new highly flexible and tractable Bayesian approach to undertake variable selection in non-Gaussian regression models. It uses a copula decomposition for the joint distribution of observations on the dependent variable. This allows the marginal distribution of the dependent variable to be calibrated accurately using a nonparametric or other estimator. The family of copulas employed are „implicit copulas” that are constructed from existing hierarchical Bayesian models widely used for variable selection, and we establish some of their properties. Even though the copulas are high dimensional, they can be estimated efficiently and quickly using Markov chain Monte Carlo. A simulation study shows that when the responses are non-Gaussian, the approach selects variables more accurately than contemporary benchmarks. A real data example in the Web Appendix illustrates that accounting for even mild deviations from normality can lead to a substantial increase in accuracy. To illustrate the full potential of our approach, we extend it to spatial variable selection for fMRI. Using real data, we show our method allows for voxel-specific marginal calibration of the magnetic resonance signal at over 6000 voxels, leading to an increase in the quality of the activation maps.The complex interplay between ultraviolet radiation (UVR) and cutaneous viral infections in the context of cancer etiology is challenging to unravel, given the limited information on the independent association between UVR and cutaneous viral infections. Using multiple biomarkers of infection with 24 types of cutaneous human papillomavirus (HPV) and 4 types of polyomaviruses (HPyV), we investigated cross-sectional associations with recent UVR exposure, using skin pigmentation measured by spectrophotometer. Age- and sex-adjusted associations between UVR and viral seropositivity, viral DNA present in eyebrow hairs (EBH) and skin swabs (SSW) were estimated using logistic regression. Beta-HPV seropositivity was associated with viral DNA positivity in EBH (OR = 1.40, 95% CI = 1.05-1.88) and SSW (OR = 1.86, 95% CI = 1.25-2.74). Similar associations were observed for Merkel cell polyomavirus. Participants in the highest tertile of UVR exposure were more likely to be seropositive for beta-HPV (OR = 1.81, 95% CI = 1.16-2.38), and have beta-HPV DNA in EBH (OR = 1.57, 95% CI = 1.06-2.33) and SSW (OR = 2.22, 95% CI = 1.25-3.96), compared to participants with the lowest tertile of UVR exposure. UVR exposure was positively associated with three different markers of beta-HPV infection. Therefore, future studies of HPV associated KC development should address more directly the role of HPV and UVR exposure as potential co-carcinogens.The current study presents two different approaches with a view to elucidating the interaction between thyroid hormones (TH) and apo-transferrin (aTf) and their role in myelination and remyelination. First, in vitro assays were conducted to determine the single and combined effects of aTf and triiodothyronine (T3) on oligodendroglial cell lineage proliferation and oligodendrocyte (OLG) maturation in primary cultures. Results revealed higher proliferation rates upon single aTf treatment but Control values upon T3 and aTf + T3 treatments. In addition, both aTf and T3 accelerated OLG maturation, with the greatest effects being exerted by combined aTf + T3 administration in terms of both myelin basic protein (MBP) expression and morphological complexity. Second, in vivo assays were carried out to establish single and combined effects of aTf and T3, as well as TH receptor (THR) inhibitor I-850, on remyelination following a CPZ-induced demyelination protocol. Results showed an increase in myelin deposition and the number of mature remyelinating OLG upon single treatments, but a synergic effect upon combined aTf + T3 treatment which was prevented by THR inhibition. It may be thus concluded that combined treatment yielded the most beneficial effects on OLG maturation parameters in vitro and remyelinating capacity in vivo when compared to single treatments. These findings may help explore the development of new target molecules in the treatment of demyelinating diseases.Withdrawal Primary prevention of sickle cell disease using preimplantation genetic testing and in vitro fertilization is cost-effective. The above article, published online on 20 August 2020 in Wiley Online Library (wileyonlinelibrary.com) as an Accepted Article, has been withdrawn by agreement between the authors, the journal Editor in Chief, and John Wiley & Sons Ltd. The article has been withdrawn after the accepted article was posted online, the authors received independent feedback that has prompted them to review their analysis in the article to ensure that the original conclusions are accurate.Desirable system performance in the face of threats has been characterized by various management concepts. Through semistructured interviews with editors of journals in the fields of emergency response and systems management, a literature review, and professional judgment, we identified nine related and often interchangeably used system performance concepts adaptability, agility, reliability, resilience, resistance, robustness, safety, security, and sustainability. A better understanding of these concepts will allow system planners to pursue management strategies best suited to their unique system dynamics and specific objectives of good performance. We analyze expert responses and review the linguistic definitions and mathematical framing of these concepts to understand their applications. We find a lack of consensus on their usage between interview subjects, but by using the mathematical framing to enrich the linguistic definitions, we formulate comparative visualizations and propose distinct definitions for the nine concepts. We present a conceptual framing to relate the concepts for management purposes.

Skeletal muscle relaxation has been primarily studied by assessing the kinetics of force decay. Little is known about the resultant dynamics of structural changes in myosin heads during relaxation. The naturally occurring nucleotide 2-deoxy-ATP (dATP) is a myosin activator that enhances cross-bridge binding and kinetics. X-ray diffraction data indicate that with elevated dATP, myosin heads were extended closer to actin in relaxed muscle and myosin heads return to an ordered, resting state after contraction more quickly. Molecular dynamics simulations of post-powerstroke myosin suggest that dATP induces structural changes in myosin heads that increase the surface area of the actin-binding regions promoting myosin interaction with actin, which could explain the observed delays in the onset of relaxation. This study of the dATP-induced changes in myosin may be instructive for determining the structural changes desired for other potential myosin-targeted molecular compounds to treat muscle diseases.

Here we umay affect soleus muscle relaxation. X-ray diffraction evidence indicates that with elevated dATP, myosin heads were extended closer to actin in resting muscle. Following contraction, there is a slight but significant delay in the decay of force relative to WT muscle while the return of myosin heads to an ordered resting state was initially slower, then became more rapid than in WT muscle. Molecular dynamics simulations of post-powerstroke myosin suggest that dATP induces structural changes in myosin that increase the surface area of the actin-binding regions, promoting myosin interaction with actin. With dATP, myosin heads may remain in an activated state near the thin filaments following relaxation, accounting for the delay in force decay and the initial delay in recovery of resting head configuration, and this could facilitate subsequent contractions.Gastric cancer (GC) is the sixth most common malignancy and the third leading cause of cancer-related death worldwide. Emerging evidence suggests that tumour microenvironment cells play a vital role in the development and prognosis of GC. To investigate the possible effect of stromal scores and immune scores on the overall survival (OS) on the GC patients, we divided GC patients into 'high’ and 'low’ groups based on their stromal and immune scores, and found differentially expressed genes related to prognosis of GC patients. Functional enrichment analysis and GSVA further revealed that focal adhesion and ECM-receptor interaction are associated with GC patients’ survival. Finally, we analysed the effects of genes commonly involved in focal adhesion and ECM-receptor interaction on GC patients’ survival and validated our results in another GC cohort from GEO data sets. In conclusion, we obtained a list of tumour microenvironment-related genes that predict poor prognosis in GC patients.Familial Mediterranean fever (FMF) is a recessive autoinflammatory disease, mainly occurring in the eastern Mediterranean. In these populations, the five FMF founder mutations are differently distributed. In Algeria, the FMF-causing variants remain poorly explored. This retrospective study aims to report the mutational profile of Algerian FMF patients and to compare it with North African FMF patients. One hundred eighty-three unrelated patients clinically suspected of FMF were recruited from various Algerian hospitals (2007-2015) and tested for mutations in exon 10 of MEFV gene. Molecular analysis identified 144 mutant alleles among 87 of 183 patients (47.5%). p.M694I was the most prevalent pathogenic allele, accounting for 63.2% of mutant alleles, followed by p.M694V and p.M680I occurring with a same frequency (14.5%). Others, p.A744S (6.2%) and p.I692del (1.3%), are less frequent. Interestingly, p.M694I was the most recurrent in patients with renal AA-amyloidosis. Our results provide the first genetic data on FMF in Algeria, demonstrating the predominance of p.M694I and the absence of p.V726A, compared to other North African countries (Morocco, Tunisia, and Egypt). In conclusion, North African FMF patients display differential mutational profiles that may result from the difference in ethnic origin and the genetic heterogeneity among these populations.Verbal aggression victimization, such as homophobic name-calling, has been linked to heavier substance use among young people, but little longitudinal research has examined how different types of victimization may affect substance use or whether certain psychosocial factors moderate these risks. In a diverse cohort (N  = 2,663), latent transition analysis was used to model heterogeneity in victimization (age 19) and substance use (age 20). Four victimization (high victimization, homophobic name-calling only, verbal sexual harassment only, and low victimization) and three substance use (poly-substance use, alcohol, and cannabis only, low all) classes were identified. The high victimization and homophobic name-calling only classes had the highest probabilities of transitioning into the poly-substance use class, and the high victimization class had the highest probability of transitioning into the alcohol and cannabis only class. The probability of transitioning into the low all substance use class was highest in the low victimization class and lowest in the high victimization class. For the high victimization class, greater depressive symptoms increased the odds, and better peer relationship quality decreased the odds, of transitioning into the poly-substance use and alcohol and cannabis only classes. For the homophobic name-calling only class, greater depressive symptoms increased the odds of transitioning into the poly-substance use class. Homophobic name-calling, alone or in combination with verbal sexual harassment, is a risk factor for escalating substance use in young adulthood, especially among victims with depressive symptoms.Cell cycle of mouse embryo could be delayed by nicotinamide (NAM). Histone H3 lysine 56 (H3K56ac) acetylation plays an important role in mammalian genomic stability and the function of this modification in mouse embryos is not known. Hence, we designed to study the effects of NAM-induced oxidative stress on the developmental ability of mouse embryos, on the acetylation of H3K56ac and the possible functions of this modification related to mouse embryo development. Treatment with NAM (10, 20, or 40 mmol/L for 24 or 48 hr) during in vitro culture significantly decreased developmental rate of blastocyst (24 hr 90.2 vs. 81.2, 43.2, and 18.2, with p > .05, p  less then  .01, respectively; 48 hr 89.3 vs. 53.2%, 12.1%, and 0% with p  less then  .05, respectively). NAM treatment (20 mmol/L) for 6 and 31 hr resulted in increased intracellular reactive oxygen species levels in two-cell embryos, and apoptotic cell numbers in blastocysts. Resveratrol (RSV) and I-CBP112 rescued the 20 mmol/L NAM-induced embryo developmental defects. RSV and I-CBP112 increased the level of Sirt1 and decreased the level of H3K56ac induced by NAM in two-cell embryos (p  less then  .05). These data suggest that NAM treatment decreases the expression of Sirt1, which induces high levels of H3K56 acetylation that may be involved in oxidative stress-induced mouse embryo defects, which can be rescued by RSV and I-CBP112.Current pulpotomy is limited in its ability to induce regeneration of the dental-pulp (DP) complex. Hydrogels are reported to be well-suited for tissue engineering and are unlikely to induce an inflammatory response that might damage the remaining tissue. The present study investigated the molecular and cellular actors in the early inflammatory/immune response and deciphered M1/M2 macrophage polarisation to a chitosan-enriched fibrin hydrogel in pulpotomised rat incisors. Both fibrin and fibrin-chitosan hydrogels induced a strong increase in interleukin-6 (IL-6) transcript in the DP when compared to the DP of untreated teeth. Gene expression of other inflammatory mediators was not significantly modified after 3 h. In the viable DP cell population, the percentage of leukocytes assessed by flow cytometry was similar to fibrin and fibrin-chitosan hydrogels after 1 d. In this leukocyte population, the proportion of granulocytes increased beneath both hydrogels whereas the antigen-presenting cell, myeloid dendritic cells, T cells and B cells decreased. The natural killer (NK) cell population was significantly decreased only in DPs from teeth treated with fibrin-chitosan hydrogel. Immunolabeling analysis of the DP/hydrogel interface showed accumulation of neutrophil granulocytes in contact with both hydrogels 1 d after treatment. The DP close to this granulocyte area contained M2 but no M1 macrophages. These data collectively demonstrated that fibrin-chitosan hydrogels induced an inflammatory/immune response similar to that of the fibrin hydrogel. The results confirmed the potential clinical use of fibrin-chitosan hydrogel as a new scaffold for vital-pulp therapies.The evidence base is growing regarding proximal fibular osteotomy. Most studies show that the pain relief and improvement in terms of radiology is statistically significant. More understandable biomechanical theories explaining this improvement are appearing. Because it has a low complication rate and is relatively easy to execute, proximal fibular osteotomy should definitely be considered in any algorithm for the treatment of medial compartment osteoarthritis of the knee. [Orthopedics. 2020;43(6)e627-e631.].The „July effect” refers to the assumed increased risk of complications during the months when medical school graduates transition to residency programs. The actual existence of a July effect is controversial. With this study, the authors sought to determine whether evidence exists for the presence of a July effect among total joint arthroplasty (TJA) procedures. The 2013 and 2014 Nationwide Readmission Databases were combined and all index primary and revision arthroplasty procedures were identified, and then patients from December were excluded. Thirty-day readmission rates, time to readmission, and readmission costs were analyzed by index procedure month and index procedure type. A total of 1,193,034 procedures (index primary n=1,107,657; revision arthroplasty n=85,377) were identified. Among all procedure types, 46,674 (3.9%) 30-day readmissions were observed. Among all procedures, an index procedure with a discharge in July resulted in the highest monthly readmission rate of the year (4.2%), which was significantly higher than the mean annual readmission rate (P less then .0001). This effect was most pronounced for primary total knee arthroplasty (3.9% vs 3.6%, P less then .0001). When stratifying results into teaching vs nonteaching hospitals, the highest readmission rate occurred if the index procedure occurred at a nonteaching hospital in July (4.5%, P less then .0001). These data provide evidence that a July effect appears to exist for TJA procedures and is most pronounced at nonteaching institutions. Based on published mean readmission costs, the total annualized cost variation attributable to the higher readmission rate for primary TJA procedures in July is approximately $18.6 million. [Orthopedics. 2020;43(6)e543-e548.].Patellar crepitus and clunk (PCC) is a known complication in total knee arthroplasty (TKA) and the cause of dissatisfaction. Patellofemoral articulations have reportedly been optimized in newer TKAs. This study compared the incidence of PCC between a historical and modern TKA design. A single-surgeon retrospective review of primary PFC Sigma (DePuy Synthes, Warsaw, Indiana) or Attune TKA (DePuy Synthes) was performed. A total of 114 PFC Sigma and 103 Attune implants were analyzed at a mean 3.2 years follow-up for overall PCC, painful PCC, anterior knee pain (regardless of crepitus), and PCC necessitating revision. Similar rates of overall PCC (14.6% vs 20.2%, P=.803), painful PCC (8.7% vs 6.1%, P=.605), and anterior knee pain (15.5% vs 9.7%, P=.219) were observed in the Attune and PFC Sigma groups, respectively. No clinically significant differences in range of motion, pain, or Knee Society Scores were found between groups. Subgroup analyses of mobile vs fixed bearing PFC Sigma implants demonstrated higher rates of overall PCC (32.