We then demonstrate how applying knowledge of community dynamics at local scales can aid management strategies to slow the degradation of coral reefs until carbon emissions and other human impacts are properly managed.

The purpose of this article is to discuss the considerations that need to be evaluated when considering the replacement of an existing maxillary anterior fixed dental prosthesis (FDP) with another FDP, or when to consider converting to implants and individual crowns on the previous abutment teeth.

The need to replace unesthetic or failing maxillary anterior FDPs is something all restorative dentists will be faced with multiple times in their careers. Given the emphasis over the past few decades on utilizing implants for tooth replacement as opposed to a tooth supported FDP, the question becomes when is converting the existing FDP to implants and single crowns an appropriate choice, as opposed to redoing a new FDP. This article will focus on the risks of choosing to convert to an implant solution, and the risks of redoing the tooth supported FDP. Multiple systematic reviews on each approach will be used to aid in the decision process. The most significant risks for both approaches will be identified, and alace an FDP, but when an existing FDP exists, the teeth have already been prepared for full coverage in most instances. In addition, for most long term existing FDPs, there is a significant change in the vertical and horizontal dimension of the bone and soft tissue that can make getting an acceptable esthetic result with an implant challenging. This article provides a systematic approach to identifying when redoing the FDP may be preferable, or when converting to an implant-based approach is a better choice.The detrimental ecological impacts of engineered shoreline protection methods (e.g., seawalls) and the need to protect the coastal zone have prompted calls for greater use of natural and nature-based infrastructure (NNBI). To balance competing needs of structural stability and ecological functioning, managers require assessments of NNBI designs and materials for differing environmental settings (e.g., among wave-energy regimes). To examine the effects of setting and oyster-based NNBI design on the provision of shoreline protection, we constructed reefs from two substrates a novel, biodegradable material (Oyster Catcher, OC) and traditional oyster shell bags (SB) on low- and high-energy eroding salt marsh shorelines, designated based on fetch and boat wake exposure. Both reef types buffered marsh elevation change on the high-energy shoreline relative to unaltered controls, but only SB reefs were able to do so on the low-energy shoreline. Additionally, both shorelines experienced high ambient rates of retreat aalternative restoration substrates to provide valuable oyster habitat along threatened marsh shorelines.As a result of climate change, abiotic stresses are the most common cause of crop losses worldwide. Abiotic stresses significantly impair plants’ physiological, biochemical, molecular and cellular mechanisms, limiting crop productivity under adverse climate conditions. However, plants can implement essential mechanisms against abiotic stressors to maintain their growth and persistence under such stressful environments. In nature, plants have developed several adaptations and defence mechanisms to mitigate abiotic stress. Moreover, recent research has revealed that signalling molecules like hydrogen sulfide (H2 S) play a crucial role in mitigating the adverse effects of environmental stresses in plants by implementing several physiological and biochemical mechanisms. Mainly, H2 S helps to implement antioxidant defence systems, and interacts with other molecules like nitric oxide (NO), reactive oxygen species (ROS), phytohormones, etc. These molecules are well-known as the key players that moderate the adverse effects of abiotic stresses. Currently, little progress has been made in understanding the molecular basis of the protective role of H2 S; however, it is imperative to understand the molecular basis using the state-of-the-art CRISPR-Cas gene-editing tool. Subsequently, genetic engineering could provide a promising approach to unravelling the molecular basis of stress tolerance mediated by exogenous/endogenous H2 S. Here, we review recent advances in understanding the beneficial roles of H2 S in conferring multiple abiotic stress tolerance in plants. Further, we also discuss the interaction and crosstalk between H2 S and other signal molecules; as well as highlighting some genetic engineering-based current and future directions.Plant-soil feedback (PSF) can be a major driver of plant performance in communities, and this concept can be used in selecting crop rotation sequences to maximize agricultural yields. Potential benefits of using PSF in this context include nutrient use optimization, pathogen reduction, and enhancement of mutualisms between crops and microbes. Yet the contributions of these combined mechanisms are poorly understood. Here we investigated the relative contributions of these mechanisms using five major crops commonly cultivated in rotation (alfalfa, canola, maize, soybean, and wheat) under controlled conditions. We trained soil by growing each of the five crops in a „training phase,” and then reciprocally planted the five crops in the trained soils in a „feedback phase.” To tease out soil biota from nutrient effects, we established three treatments „control” (trained unsterilized soil used in the feedback phases), „biota” (sterilized soil in the feedback phase inoculated with soil biota from the control treatmentgether, our data demonstrate how nutrients and soil biota can be integral to PSFs among crops, and that assessing PSFs under controlled conditions can serve as a basis to determine the most productive crop rotation sequences prior to field testing.Symbiotic nitrogen fixation in legumes is an important source of nitrogen supply in sustainable agriculture. Salinity is a key abiotic stress that negatively affects host plant growth, rhizobium-legume symbiosis and nitrogen fixation. This work investigates how the symbiotic relationship impacts plant response to salinity stress. We assayed the physiological changes and the proteome profile of alfalfa plants with active nodules (NA), inactive nodules (NI) or without nodules (NN) when plants were subjected to salinity stress. Our data suggest that NA plants respond to salinity stress through some unique signalling regulations. NA plants showed upregulation of proteins related to cell wall remodelling and reactive oxygen species scavenging, and downregulation of proteins involved in protein synthesis and degradation. The data also show that NA plants, together with NI plants, upregulated proteins involved in photosynthesis, carbon fixation and respiration, anion transport and plant defence against pathogens. The study suggests that the symbiotic relationship gave the host plant a better capacity to adjust key processes, probably to more efficiently use energy and resources, deal with oxidative stress, and maintain ion homeostasis and health during salinity stress.

Combining genetic variants with neuroimaging phenotypes may facilitate understanding of the biological mechanisms for the etiology and pharmacology of antidepressant treatment of major depressive disorder (MDD).

To explore the latent pathway of dopamine gene-hierarchical brain network-antidepressant treatment.

Retrospective.

One hundred and sixty-eight MDD inpatients divided into responders (N=98) or nonresponders (N=70) based on the treatment outcome of antidepressant.

Diffusion tensors imaging and resting-state functional magnetic resonance imaging at 3.0T using echo-planar sequence.

Four genetic variations of the dopamine receptor D1 (DRD1) were genotyped. Strengths of rich-club, feeder, and local connections were calculated based on the rich-club organizations of structural and functional brain networks at baseline and following 4 weeks of selective serotonin reuptake inhibitor (SSRI) therapy.

Logistic and linear regressions were used to analyze the impact of DRD1 multilocus genetic profile score on the treatment response of SSRI, and their associations with strengths of rich-club, feeder, and local connections. Mediation models were developed to explore the mediation role of rich-club organizations on the relationship between DRD1 and SSRI therapy response. A P value <0.05 was considered to be statistically significant.

Multiple genetic variations of DRD1 were significantly related to the strengths of feeder connections both in structural and functional networks, and to the treatment response of SSRI. Furthermore, the strength of the structural feeder connection significantly modulated the effect of DRD1 variants on SSRI treatment outcome.

DRD1 displayed close connections both with SSRI treatment outcome and rich-club organizations of structural and functional data. Moreover, structural feeder connection played a mediating role in the relationship between DRD1 and antidepressant therapy.

3 TECHNICAL EFFICACY STAGE 4.

3 TECHNICAL EFFICACY STAGE 4.Manufactured globally on industrial scale, cyclodextrins (CD) are cyclic oligosaccharides produced by enzymatic conversion of starch. Their typical structure of truncated cone can host a wide variety of guest molecules to create inclusion complexes; indeed, we daily use CD as unseen components of food, cosmetics, textiles and pharmaceutical excipients. The synthesis of active material composites from CD resources can enable or enlarge the effective utilization of these products in the battery industry with some economical as well as environmental benefits. New and simple strategies are here presented for the synthesis of nanostructured silicon and sulfur composite materials with carbonized hyper cross-linked CD (nanosponges) that show satisfactory performance as high-capacity electrodes. For the sulfur cathode, the mesoporous carbon host limits polysulfide dissolution and shuttle effects and guarantees stable cycling performance. The embedding of silicon nanoparticles into the carbonized nanosponge allows to achieve high capacity and excellent cycling performance. Moreover, due to the high surface area of the silicon composite, the characteristics at the electrode/electrolyte interface dominate the overall electrochemical reversibility, opening a detailed analysis on the behavior of the material in different electrolytes. We show that the use of commercial LP30 electrolyte causes a larger capacity fade, and this is associated with different solid electrolyte interface layer formation and it is also demonstrated that fluoroethylene carbonate addition can significantly increase the capacity retention and the overall performance of our nanostructured Si/C composite in both ether-based and LP30 electrolytes. As a result, an integration of the Si/C and S/C composites is proposed to achieve a complete lithiated Si-S cell.Globozoospermia is a type of teratozoospermia characterized by round morphology of the sperm head. Gopc-/- infertile globozoospermic murine model has failures during spermiogenesis, such as the incorrect biogenesis of the acrosome, disorganized acroplaxome and manchette, round nuclei and spiral flagella. In this study, Western blot, RT-PCR, immunohistochemistry and immunogold were done for the localization of the acrosome protein Zona Pellucida sperm-binding protein 3 receptor (ZP3R), also called sp56, in wild type and Gopc-/- mice testis. The ZP3R protein was located in the acrosome and pseudo-acrosome vesicles of wild type and Gopc-/- mice, respectively. Also, it is distributed through the cytoplasm of the haploid spermatids only. The incorrect spermiogenesis of Gopc-/- mice causes a deregulation in the expression of ZP3R in the globozoospermic spermatids. Our results suggest that although the lack of GOPC causes a failure during the transport of the pre-acrosomal vesicles, the acrosome protein ZP3R is localized in the acrosome and is distributed through the cytoplasm only during spermiogenesis. Furthermore, the failure in spermiogenesis does not impair the synthesis of ZP3R and its localization in the pre-acrosomal vesicles.Cortical bone develops and changes in response to mechanical load, which is sensed by bone-embedded osteocytes. The bone formation response to load depends on STAT3 intracellular signals, which are upregulated after loading and are subject to negative feedback from Suppressor of Cytokine Signaling 3 (Socs3). Mice with Dmp1Cre-targeted knockout of Socs3 have elevated STAT3 signaling in osteocytes and display delayed cortical bone maturation characterized by impaired accrual of high-density lamellar bone. This study aimed to determine whether these mice exhibit an altered response to mechanical load. The approach used was to test both treadmill running and tibial compression in female Dmp1Cre.Socs3f/f mice. Treadmill running for 5 days per week from 6 to 11 weeks of age did not change cortical bone mass in control mice, but further delayed cortical bone maturation in Dmp1Cre.Socs3f/f mice; accrual of high-density bone was suppressed, and cortical thickness was less than in genetically-matched sedentary controlssignaling within osteocytes. © 2021 American Society for Bone and Mineral Research (ASBMR).Because of their rarity, diseases characterized by chronic hypophosphatemia can be underrecognized and suboptimally managed, resulting in poor clinical outcomes. Moreover, serum phosphate may not be measured routinely in primary care practice. Authors participated in several working sessions to advance the understanding of phosphate homeostasis and the causes, consequences, and clinical implications of chronic hypophosphatemia. Phosphate levels are regulated from birth to adulthood. Dysregulation of phosphate homeostasis can result in hypophosphatemia, which becomes chronic if phosphate levels cannot be normalized. Chronic hypophosphatemia may be underrecognized as serum phosphate measurement is not always part of routine analysis in the primary care setting and results might be misinterpreted, for instance, due to age-specific differences not being accounted for and circadian variations. Clinical consequences of chronic hypophosphatemia involve disordered endocrine regulation, affect multiple organ systems, ).A phenanthrene unit has been functionalized by several methylthiophene units in order to bring it a photochromic behavior. These compounds were characterized by NMR, absorption and emission spectroscopies, theoretical calculations as well as cyclic voltammetry. The association of a phenanthrene group with a photochromic center could open the door to a new generation of organic field-effect transistors.

To evaluate how effective preparatory interventions for paediatric day surgery are at reducing parents’ anxiety and stress and children’s pain and fear.

A systematic review was conducted according to Joanna Briggs Institute (JBI) guidelines and reported using the PRISMA 2020 checklist. PubMed, CINAHL (EBSCO), Scopus, Medic and Web of Science were screened for original research published up until December 2020, while Mednar and EBSCO Open Dissertations were used to identify any relevant grey literature. The methodological quality and risks of bias were evaluated according to JBI guidelines by two authors. The eligibility criteria were parents of a preschool (2- to 6-year-old) child going through day surgery with preparatory interventions, outcomes measured anxiety, stress (parent), fear and pain (child), and randomised controlled trial (RCT).

Two thousand and three hundred and fourteen RCTs were screened. Fifteen studies (including 1514 participants) were chosen for narrative synthesis of parental anxiet interventions can reduce anxiety among parents and postoperative pain in children.

Applying machine-learning algorithms to large datasets such as those available in Huntington’s disease offers the opportunity to discover hidden patterns, often not discernible to clinical observation.

To develop and validate a model of Huntington’s disease progression using probabilistic machine learning methods.

Longitudinal data encompassing 2079 assessment measures from four observational studies (PREDICT-HD, REGISTRY, TRACK-HD, and Enroll-HD) were integrated and machine-learning methods (Bayesian latent-variable analysis and continuous-time hidden Markov models) were applied to develop a probabilistic model of disease progression. The model was validated using a separate Enroll-HD dataset and compared with existing clinical reference assessments (Unified Huntington’s Disease Rating Scale [UHDRS] diagnostic confidence level, total functional capacity, and total motor scores) and CAG-age product.

Nine disease states were discovered based on 44 motor, cognitive, and functional measures, which correlo derive characteristics of disease states and probabilities for progression through these states will improve trial design and participant selection. © 2021 International Parkinson and Movement Disorder Society.The crossbred dairy cattle (CDC) have been gaining popularity in the tropical countries for their increased milk yield within a short period of time because of heterogenic additive gene action. Hence, we aimed to investigate whether genotype, parity, season and their interactions had any effect on average daily milk yield (ADMY) of the CDC in a dairy farm at Chattogram district, Bangladesh, for a period of 3 years from January 2016 to December 2019. Total 16,425 retrospective lactation records of 150 multiparous Sahiwal × Friesian1 (Sahiwal = 50%, HF = 50%), Local × Friesian1 (Local = 50%, HF = 50%) and Local × Friesian2 (Local = 25%, HF = 75%) CDC from the first to the third parities (50 for each parity) were collected from the farm records. The generalized linear model and principal component analysis identified substantial impacts of genotype, parity, season and their interactions on ADMY of the CDC. The herd level least squared ADMY was 11.22 ± 0.04 kg/days on a 305-days typical lactation period. The Sahiwal × Friesian1 CDC produced 7.2% and 5.5% more milk than the Local × Friesian1 and Local × Friesian2 respectively. The CDC produced maximum milk in the second parity, which was 7.8% and 0.34% more than the first and third parities. Similarly, the highest ADMY was recorded in the spring, which was 10.8%, 7.3% and 6.6% more than the fall, summer and winter respectively. It was concluded that the Sahiwal × Friesian1 crossbred produced maximum milk in the spring season at the second parity while other determinants remained constant. The changing patterns of milk yield in different genotype, parity and seasons provided scientific evidence for improving feeding strategy to optimize herd level milk yield of CDC in the commercial dairy farms under tropical perspective.Carbon nitrides are among the most studied materials for photocatalysis; however, limitations arise from inefficient charge separation and transport within the material. Here, this aspect is addressed in the 2D carbon nitride poly(heptazine imide) (PHI) by investigating the influence of various counterions, such as M = Li+ , Na+ , K+ , Cs+ , Ba2+ , NH4 + , and tetramethyl ammonium, on the material’s conductivity and photocatalytic activity. These ions in the PHI pores affect the stacking of the 2D layers, which further influences the predominantly ionic conductivity in M-PHI. Na-containing PHI outperforms the other M-PHIs in various relative humidity (RH) environments (0-42%RH) in terms of conductivity, likely due to pore-channel geometry and size of the (hydrated) ion. With increasing RH, the ionic conductivity increases by 4-5 orders of magnitude (for Na-PHI up to 10-5 S cm-1 at 42%RH). At the same time, the highest photocatalytic hydrogen evolution rate is observed for Na-PHI, which is mirrored by increased photogenerated charge-carrier lifetimes, pointing to efficient charge-carrier stabilization by, e.g., mobile ions. These results indicate that also ionic conductivity is an important parameter that can influence the photocatalytic activity. Besides, RH-dependent ionic conductivity is of high interest for separators, membranes, or sensors.Skeletal stem/progenitor cells (SSPCs) can differentiate into osteogenic or adipogenic lineage. The mechanism governing lineage allocation of SSPCs is still not completely understood. Hedgehog (Hh) signaling plays an essential role in specifying osteogenic fate of mesenchymal progenitors during embryogenesis. However, it is still unclear whether Hh signaling is required for lineage allocation of SSPCs in postnatal skeleton, and whether its dysregulation is related to age-related osteoporosis. Here, we demonstrated that Hh signaling was activated in metaphyseal SSPCs during osteogenic differentiation in the adult skeleton, and its activity decreased with aging. Inactivation of Hh signaling by genetic ablation of Smo, a key molecule in Hh signaling, in Osx-Cre-targeted SSPCs and hypertrophic chondrocytes led to decreased bone formation and increased bone marrow adiposity, two key pathological features of age-related osteoporosis. Moreover, we found that the bone-fat imbalance phenotype caused by Smo deletion mainly resulted from aberrant allocation of SSPCs toward adipogenic lineage at the expense of osteogenic differentiation, but not due to accelerated transdifferentiation of chondrocytes into adipocytes. Mechanistically, we found that Hh signaling regulated osteoblast versus adipocyte fate of SSPCs partly through upregulating Wnt signaling. Thus, our results indicate that Hh signaling regulates bone homeostasis and age-related osteoporosis by acting as a critical switch of cell fate decisions of Osx-Cre-targeted SSPCs in mice and suggest that Hh signaling may serve as a potential therapeutic target for the treatment of osteoporosis and other metabolic bone diseases. © 2021 American Society for Bone and Mineral Research (ASBMR).One of the worrying concomitants of problematic use of Internet (PUI) is aggression. Although the mechanisms underlying such link have not been completely clarified, it has been suggested that problematic use of social media and online videogames (i.e., two common forms of PUI among young adults) lead to increased sleep disturbances which, in turn, represent a relevant trigger for aggression. We have tested this hypothesis in a sample (N = 480) of young individuals (351 females and 129 males; mean age 21.76 ± 1.92 years; range 18-24). Self-report measures investigating symptoms related to social media addiction (SMA), Internet gaming disorder (IGD), insomnia severity, and aggression were used. Mediational models analyzing the direct and indirect associations of SMA- and IGD-related symptoms on aggression severity through insomnia-related symptoms were performed controlling for confounding factors. The models showed that the total effects of SMA-related symptoms (B = 0.018; p = .010) and of IGD-related symptoms (B = 0.018; p = .041) on aggression severity were significant and that these associations were mediated by insomnia-related symptoms (respectively, p  less then  .001 and p = .003). Our findings support the potential mediating role of insomnia severity in the association of SMA- and IGD-related disturbances with levels of aggression.

Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours with malignant potential and a hereditary basis in almost 40% of patients. Germline genetic testing has transformed the management of PPGL enabling stratification of surveillance approaches, earlier diagnosis and predictive testing of at-risk family members. Recent studies have identified somatic mutations in a further subset of patients, indicating that molecular drivers at either a germline or tumour level can be identified in up to 80% of PPGL cases. The aim of this study was to investigate the clinical utility of somatic sequencing in a large cohort of patients with PPGL in the United Kingdom.

Prospectively collected matched germline and tumour samples (development cohort) and retrospectively collected tumour samples (validation cohort) of patients with PPGL were investigated.

Clinical characteristics of patients were assessed and tumour and germline DNA was analysed using a next-generation sequencing strategy. A screen foreted therapeutic strategies for patients with metastatic disease.

This study aimed to verify racial differences in the performance of Dental Specialities Centers in Brazil, according to the presence of active health ombudsman on four primary outcomes (1) access and dental appointment, (2) reception services, (3) bond and responsibility, and (4) social participation.

Data came from the PMAQ-CEO national evaluation of public healthcare services, 2018-2019. The two main explanatory variables were the self-classified race at the individual level and the presence of the health ombudsman at the second level (level of services provision). Individual covariates included age, sex and schooling. Multilevel logistic regression was used to calculate the OR (Odds Ratios) in racial gaps according to the primary outcomes with individuals at the first level and public health services at the second level.

The analytical sample comprised of 8993 respondents. Brown people were less likely to report better Access (27%), good reception services (31%), bond and responsibility (30%) and social participation (22%) than Whites. Black people showed similar patterns. Dental Specialities Centers that use health ombudsman for planning have attenuated racial inequities in all analysed dimensions.

Dental Specialities Centers that use active health ombudsman for planning showed lower racial inequities in access, reception, bond and responsibility and social participation than those who did not use. Therefore, the health ombudsman should be implemented and used for planning better specialized dental services in Brazil.

Dental Specialities Centers that use active health ombudsman for planning showed lower racial inequities in access, reception, bond and responsibility and social participation than those who did not use. Therefore, the health ombudsman should be implemented and used for planning better specialized dental services in Brazil.

Postoperative complications may depend on the systemic inflammatory response. We evaluated the predictive potential of the combination of platelet count and neutrophil-to-lymphocyte ratio (COP-NLR) for the incidence of pharyngocutaneous fistula (PCF) in patients who have undergone total laryngectomy.

Retrospective cohort study.

Patients who underwent total laryngectomy between 2000 and 2020 were recruited from four hospitals. The correlations between the incidence of PCF and several risk factors, including the COP-NLR, were examined. Patients with both elevated platelet count and elevated neutrophil-to-lymphocyte ratio (NLR) were categorized as COP-NLR 2, and patients with either one or no abnormal values of both parameters were assigned as COP-NLR 1 and COP-NLR 0, respectively.

A total of 235 patients were identified. The overall incidence of PCF was 12.3%. The cut-off value for NLR before surgery was set at 3.95 (sensitivity=58.6%, specificity=69.4%, area under the curve [AUC]=0.635), and the platelet count was set at 320 × 10

/L (sensitivity=27.6%, specificity=87.9%, AUC=0.571). Multivariate analysis revealed that COP-NLR was an independent risk factor for PCF (COP-NLR 1 vs. COP-NLR 0 odds ratio [OR], 4.17; 95% confidence interval [CI], 1.64 to 10.59; and COP-NLR 2 vs. COP-NLR 0 OR, 5.33; 95% CI, 1.38 to 20.56).

COP-NLR is a novel predictive factor for the development of PCF in patients undergoing total laryngectomy.

4 Laryngoscope, 2021.

4 Laryngoscope, 2021.Standard platelet concentrates (PCs) stored at 22°C have a limited shelf life of 5 days. Because of the storage temperature, bacterial contamination of PCs can result in life-threatening infections in transfused patients. The potential of blood components to cause infections through contaminating pathogens or transmitting blood-borne diseases has always been a concern. The current safety practice to prevent pathogen transmission through blood transfusion starts with a stringent screening of donors and regulated testing of blood samples to ensure that known infections cannot reach transfusion products. Pathogen reduction technologies (PRTs), initially implemented to ensure the safety of plasma products, have been adapted to treat platelet products. In addition to reducing bacterial contamination, PRT applied to PCs can extend their shelf life up to 7 days, alleviating the impact of their shortage, while providing an additional safety layer against emerging blood-borne infectious diseases. While a deleterious action of PRTs in quantitative and qualitative aspects of plasma is accepted, the impact of PRTs on the quality, function, and clinical efficacy of PCs has been under constant examination. The potential of PRTs to prevent the possibility of new emerging diseases to reach cellular blood components has been considered more hypothetical than real. In 2019, a coronavirus-related disease (COVID-19) became a pandemic. This episode should help when reconsidering the possibility of future blood transmissible threats. The following text intends to evaluate the impact of different PRTs on the quality, function, and clinical effectiveness of platelets within the perspective of a developing pandemic.

To characterize the clinical features, risk factors, symptom time-course, and quality of life implications for parosmia among coronavirus disease (COVID)-related olfactory dysfunction patients.

Individuals with olfactory dysfunction associated with laboratory-confirmed or clinically suspected COVID-19 infection were recruited from otolaryngology and primary care practices over a period from August 2020 to March 2021. Participants completed olfactory dysfunction and quality of life surveys.

A total of 148 (64.1%) of 231 respondents reported parosmia at some point. Parosmia developed within 1week of any COVID-19 symptom onset in 25.4% of respondents, but more than 1month after symptom onset in 43.4% of respondents. Parosmia was associated with significantly better quantitative olfactory scores on Brief Smell Identification Test (8.7 vs. 7.5, P=.006), but demonstrated worse quality of life scores, including modified brief Questionnaire of Olfactory Dysfunction-Negative Statements and Sino-Nasal Outcome Test-22 scores (12.1 vs. 8.5, P < .001; 26.2 vs. 23.2, P=.113). Participants who developed parosmia at any point were significantly younger and less likely to have history of chronic sinusitis than those who did not develop parosmia (40.2 vs. 44.9 years, P=.007; 7.2% vs. 0.7%, P=.006).

COVID-19-associated olfactory dysfunction is frequently linked with development of parosmia, which often presents either at onset of smell loss or in a delayed fashion. Despite better quantitative olfactory scores, respondents with parosmia report decreased quality of life. A majority of respondents with persistent parosmia have sought treatment.

3 Laryngoscope, 132633-639, 2022.

3 Laryngoscope, 132633-639, 2022.Aspergillus fumigatus, a ubiquitous pathogen, causes aspergillosis in humans, especially in immunodeficient patients. Azoles are frontline antifungal drugs for treating aspergillosis. The recent global emergence of azole resistance in A. fumigatus has become a serious problem worldwide. It has arisen through two routes long-term azole medical therapy, called the patient route, and the use of azole fungicides in its habitats especially for agricultural activities, called the environmental route. Resistant strains developed through the latter route show cross-resistance to medical azoles because of the identical molecular target Cyp51A between azole compounds used for medical treatment and agricultural disease control. In azole-resistant strains arising through the environmental route, A. fumigatus is observed frequently to possess mutations in the cyp51A gene linked to tandem repeats in the promoter region such as TR34 /L98H and TR46 /Y121F/T289A. The results of microsatellite genotyping analyses of resistant A. fumigatus strains have suggested a transboundary spread of this microorganism in many countries. Diverse actors are involved in the global highway of transmission. Therefore, the matter must be addressed as a „One Health” issue. This review presents a background of azole resistance in A. fumigatus and introduces newly discovered difficulties generated as this pathogen spreads worldwide.There has been tremendous advancement in machine learning (ML) applications in computational chemistry, particularly in neural network potentials (NNP). NNPs can approximate potential energy surface (PES) as a high dimensional function by learning from existing reference data, thereby circumventing the need to solve the electronic Schrödinger equation explicitly. As a result, ML accelerates chemical space exploration and property prediction compared to quantum mechanical methods. Novel ML methods have the potential to provide efficient means for predicting the properties of molecules. However, this potential has been limited by the lack of standard comparative evaluations. In this work, we compare four selected models, that is, ANI, PhysNet, SchNet, and BAND-NN, developed to represent the PES of small organic molecules. We evaluate these models for their accuracy and transferability on two different test sets (i) Small organic molecules of up to eight-heavy atoms on which ANI and SchNet achieve root mean square error (RMSE) of 0.55 and 0.60 kcal/mol, respectively. (ii) On random selection of molecules from the GDB-11 database with 10-heavy atoms, ANI achieves RMSE of 1.17 kcal/mol and SchNet achieves RMSE of 1.89 kcal/mol. We examine their ability to produce smooth meaningful surface by performing PES scans for bond stretch, angle bend, and dihedral rotations on relatively large molecules to assess their possible application in molecular dynamics simulations. We also evaluate their performance for yielding minimum energy structures via geometry optimization using various minimization algorithms. All these models were also able to accurately differentiate different isomers of the same empirical formula C 10 H 20 . ANI and PhysNet achieve an RMSE of 0.29 and 0.52 kcal/mol, respectively, on C 10 H 20 isomers.

The aim of this study was to evaluate whether clinical attachment level gain (ΔCAL) in deep untreated periodontal lesions may be improved by a two-stage, subgingival instrumentation scheme involving air polishing.

This 6-month, randomized, controlled, examiner-masked clinical trial was performed in 44 patients with periodontitis with untreated periodontal lesions ≥6mm. At baseline, day 28, 84, and 168 CAL, probing depth (PD), bleeding on probing (BOP), and plaque control record (PlaCR) were recorded. After baseline examination control group patients received full-mouth sub- and supragingival instrumentation using scalers and curets. In the test group initial subgingival cleaning was limited to the removal of soft bacterial deposits by air polishing. Subgingival scaling and root planing was performed only after the first re-evaluation at day 28.

In deep lesions ≥6 mm a significant reduction of mean CAL scores was observed at day 28 and at day 168 for both experimental groups. Differences between the groups however did not reach the level of significance. Mean PD was also significantly reduced at day 28 and at 168 in both experimental groups, with no significant differences between the groups. Mean BOP scores did not change significantly in both groups during the 168-day observation period. Only in the test group mean PlaCR scores were significantly reduced at day 168 compared with baseline.

Subgingival instrumentation of untreated PD ≥6 mm by air polishing alone results in a significant short-term gain of CAL comparable to conventional scaling and root planing. Its sequential two-step combination with scaling and root planing, however, does not additionally enhance long-term gain of CAL.

Subgingival instrumentation of untreated PD ≥6 mm by air polishing alone results in a significant short-term gain of CAL comparable to conventional scaling and root planing. Its sequential two-step combination with scaling and root planing, however, does not additionally enhance long-term gain of CAL.

Military personnel and frontline emergency workers may be exposed to events that have the potential to precipitate negative mental health outcomes such as depression, symptoms of post-traumatic stress and even post-traumatic stress disorder (PTSD). Programmes have been designed to build psychological resilience before staff are deployed into the field. This review presents a synthesis of the literature on these „pre-deployment resilience-building programmes”.

The objective of this review was to assess the effectiveness of programmes that seek to build resilience to potentially traumatic events among military and frontline emergency service personnel prior to their deployment. These resilience programmes were compared to other interventions, treatment as usual or no intervention.

Studies were identified through searches of electronic databases including Ovid MEDLINE, Embase, PsycINFO, Web of Science and Google Scholar. The initial search took place in January 2019, with an updated search completed at theexpectations in relation to the efficacy of resilience-building programmes as a prophylactic approach to employment-related critical incident traumas.To better understand the mechanisms at the basis of neutrophil functions during SARS-CoV-2, we studied patients with severe COVID-19 pneumonia. They had high blood proportion of degranulated neutrophils and elevated plasma levels of myeloperoxidase (MPO), elastase, and MPO-DNA complexes, which are typical markers of neutrophil extracellular traps (NET). Their neutrophils display dysfunctional mitochondria, defective oxidative burst, increased glycolysis, glycogen accumulation in the cytoplasm, and increase glycogenolysis. Hypoxia-inducible factor 1α (ΗΙF-1α) is stabilized in such cells, and it controls the level of glycogen phosphorylase L (PYGL), a key enzyme in glycogenolysis. Inhibiting PYGL abolishes the ability of neutrophils to produce NET. Patients displayed significant increases of plasma levels of molecules involved in the regulation of neutrophils’ function including CCL2, CXCL10, CCL20, IL-18, IL-3, IL-6, G-CSF, GM-CSF, IFN-γ. Our data suggest that metabolic remodelling is vital for the formation of NET and for boosting neutrophil inflammatory response, thus, suggesting that modulating ΗΙF-1α or PYGL could represent a novel approach for innovative therapies.The information of crystal structure and orientation can be provided by analysing the EBSD (electron backscatter diffraction) patterns which are obtained with the EBSD devices. The reliability and accuracy of the information relies on the location of bands and intersections of the EBSD patterns. In this study, a method is proposed to automatically obtain the locations and intersections of the EBSD patterns, that is, Kikuchi bands. The proposed method uses Radon transform and progressive probabilistic Hough transform to detect straight lines and line segments of the Kikuchi band edges, respectively. Then, Kikuchi bands can be presented by fitting the hyperbolas with the endpoints of line segments. The results can numerically describe the information of Kikuchi bands. Experimental results show that the method is robust and can detect more accurate Kikuchi bands and intersections.

Non-small cell lung cancer (NSCLC) is the most common lung cancer, accounting for approximately 80% to 85% of all cases. For people with localised NSCLC (stages I to III), it has been speculated that immunotherapy may be helpful for reducing postoperative recurrence rates, or improving the clinical outcomes of current treatment for unresectable tumours. This is an update of a Cochrane Review first published in 2017 and it includes two new randomised controlled trials (RCTs).

To assess the effectiveness and safety of immunotherapy (excluding checkpoint inhibitors) among people with localised NSCLC of stages I to III who received curative intent ofradiotherapy or surgery.

We searched the following databases (from inception to 19 May 2021) CENTRAL, MEDLINE, Embase, CINAHL, and five trial registers. We also searched conference proceedings and reference lists of included trials.

We included RCTs conducted in adults (≥ 18 years) diagnosed with NSCLC stage I to III after surgical resection, and those with unherapy for people with stages I to III NSCLC.

Air pollution has emerged as an important environmental risk factor for chronic rhinosinusitis (CRS) progression. This study assessed exposure to five types of air pollution (PM

, SO

, NO

, CO, O

) and explored their effects on CRS with nasal polyps (CRSwNP) severity and endotype.

Retrospective cohort study.

Air pollution data from monitoring sites in Beijing were obtained to assess individual air pollution exposure. Outcomes of CRSwNP (n=282) including Lund-Mackay (L-M) score, Lund-Kennedy (L-K) score, visual analogue scale (VAS) score and nasal patency/airflow resistance and so on were measured to analyze correlations with air pollution and compare groups with different exposure types. Multivariable-adjusted binary logistic regression was used to determine potential air pollution risk factors of the endotype of eosinophilic CRSwNP (ECRSwNP).

Short-term exposures to PM

, SO

, CO, NO

, and O

were weak but significantly associated with increased L-M scores. Short-term exposures to PM

, CO, and NO

were correlated with increased VAS headache/facial pain scores. The L-M scores of the group of the highest PM

(≥150 μg/m

) exposure were significantly higher than those of control group. For each increased unit of the average concentration of PM

, there was a 1.047-fold (95% confidence interval, 1.005-1.091) increased risk of the endotype of ECRSwNP.

Air pollution exposure exacerbated CRSwNP severity and PM

could be a risk factor for endotype of ECRSwNP, suggesting the role of air pollution in CRSwNP pathogenesis.

4 Laryngoscope, 2021.

4 Laryngoscope, 2021.

Although dermatologists treat many painful skin conditions and perform procedures that may require analgesic use, there is a lack of evidence synthesis on opioid use in dermatology.

To conduct a systematic review of the evidence on the use of opioid analgesics in dermatology.

We applied the PRISMA guidelines and systematically reviewed literature that examined opioid use in dermatology published between 1980 and 2020 in the PubMed, EMBASE, and Cochrane databases. This review was registered with PROSPERO (CRD42020204864).

We identified 24 studies that analyzed 52,705,201 patients and 13,099 dermatologists. Between 34% and 87.5% of patients received opioids following dermatologic procedures; however, many did not use the entirety of their prescriptions, and 35-69% did not use any of their prescription. Top opioid prescribers were more likely to be Mohs surgeons, male, and practice in the South. Variability exists in the current evidence for opioid prescribing for nonprocedural dermatologic disease.

While opioid prescribing in dermatology is low compared with other specialties, patients are not utilizing the entirety of their prescriptions. Opioid prescribing for nonprocedural dermatologic disease varies; treatments focused on targeting the pathogenesis of these diseases is important to minimize opioid use. Dermatologists should consider limiting opioid prescribing and utilizing nonnarcotic analgesics.

While opioid prescribing in dermatology is low compared with other specialties, patients are not utilizing the entirety of their prescriptions. Opioid prescribing for nonprocedural dermatologic disease varies; treatments focused on targeting the pathogenesis of these diseases is important to minimize opioid use. Dermatologists should consider limiting opioid prescribing and utilizing nonnarcotic analgesics.Although we earlier reported a very poor outcome for younger adult patients with isocitrate dehydrogenase 2 (IDH2)R172 -mutated acute myeloid leukaemia (AML) entered into UK trials compared to IDH2WT and IDH2R140 -mutated patients, this was not corroborated by a study from the German-Austrian AML Study Group. We have therefore investigated a later cohort of IDH2-mutated patients to identify any changes in outcome and whether this could inform the optimal treatment for IDH2R172 AML. We found an improved outcome for IDH2R172 -mutated AML in the later trials and the data suggests that this may be due to the increased use of allogeneic transplantation to consolidate first remission.Sera of vaccines were assessed by surrogate virus neutralization tests for their capacity to neutralize the SARS-CoV-2 Delta variant. Homologous prime-boost immunization with Moderna’s Spikevax as well as heterologous immunization with AstraZeneca’s Vaxzevria followed by Moderna’s Spikevax were identified as highly potent vaccination regimens for the induction of Delta-neutralizing antibodies.

Epilepsy is one of the most common neurological disorders. Many people with epilepsy are drug-resistant and require add-on therapy, meaning that they concomitantly take multiple antiepileptic drugs. Carisbamate is a drug which is taken orally and inhibits voltage-gated sodium channels. Carisbamate may be useful for drug-resistant focal epilepsy.

To evaluate the efficacy and tolerability of carisbamate when used as an add-on therapy for drug-resistant focal epilepsy.

We searched the following databases on 8 April 2021 Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) 1946 to April 07, 2021. CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, WHO ICTRP, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane review groups including Epilepsy. We also searched ongoing trials registers, checked reference lists, and contacted authors of the included trials.

Double-blind randomised controlled trialsal outcomes, more seizure types, and a broader range of participants.There is a paucity of adequate mouse models and cell lines available to study lung squamous cell carcinoma (LUSC). We have generated and characterized two models of phenotypically different transplantable LUSC cell lines, i.e. UN-SCC679 and UN-SCC680, derived from A/J mice that had been chemically induced with N-nitroso-tris-chloroethylurea (NTCU). Furthermore, we genetically characterized and compared both LUSC cell lines by performing whole-exome and RNA sequencing. These experiments revealed similar genetic and transcriptomic patterns that may correspond to the classic LUSC human subtype. In addition, we compared the immune landscape generated by both tumor cells lines in vivo and assessed their response to immune checkpoint inhibition. The differences between the two cell lines are a good model for the remarkable heterogeneity of human squamous cell carcinoma. Study of the metastatic potential of these models revealed that both cell lines represent the organotropism of LUSC in humans, i.e. affinity to the brain, bones, liver and adrenal glands. In summary, we have generated valuable cell line tools for LUSC research, which recapitulates the complexity of the human disease.Activation-induced cytidine deaminase (AID) is a member of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family of cytidine deaminases. AID mutates immunoglobulin loci to initiate secondary antibody diversification. The APOBEC3 (A3) sub-branch mutates viral pathogens in the cytosol and acidic endosomal compartments. Accordingly, AID functions optimally near-neutral pH, while most A3s are acid-adapted (optimal pH 5.5-6.5). To gain a structural understanding for this pH disparity, we constructed high-resolution maps of AID catalytic activity vs pH. We found AID’s optimal pH was 7.3 but it retained most (>70%) of the activity at pH 8. Probing of ssDNA-binding residues near the catalytic pocket, key for bending ssDNA into the pocket (e.g. R25) yielded mutants with altered pH preference, corroborating previous findings that the equivalent residue in APOBEC3G (H216) underlies its acidic pH preference. AID from bony fish exhibited more basic optimal pH (pH 7.5-8.1) and several R25-equivalent mutants altered pH preference. Comparison of pH optima across the AID/APOBEC3 family revealed an inverse correlation between positive surface charge and overall catalysis. The paralogue with the most robust catalytic activity (APOBEC3A) has the lowest surface charge and most acidic pH preference, while the paralogue with the most lethargic catalytic rate (AID) has the most positive surface charge and highest optimal pH. We suggest one possible mechanism is through surface charge dictating an overall optimal pH that is different from the optimal pH of the catalytic pocket microenvironment. These findings illuminate an additional structural mechanism that regulates AID/APOBEC3 mutagenesis.Liver cirrhosis and portal hypertension is the end of chronic liver injury with hepatic, splanchnic and portosystemic collateral systems dysregulation. Liver injury is accompanied by gut dysbiosis whereas dysbiosis induces liver fibrosis, splanchnic angiogenesis and dysregulated vascular tones vice versa, making portal hypertension aggravated. It has been proved that intestinal microbiota transplantation alleviates dysbiosis. Nevertheless, the influences of microbiota transplantation on cirrhosis-related portal hypertension are not so clear. Liver cirrhosis with portal hypertension was induced by bile duct ligation (BDL) in rats. Sham rats were surgical controls. Rats randomly received vehicle, fecal or gut (terminal ileum) material transplantation. The results showed that microbiota transplantation from feces or gut material significantly reduced portal pressure in cirrhotic rats (P=0.010, 0.044). Hepatic resistance, vascular contractility, fibrosis and relevant protein expressions were not significantly different among cirrhotic rats. However, microbiota transplantation ameliorated splanchnic hyperdynamic flow and vasodilatation. Mesenteric angiogenesis, defined by whole mesenteric window vascular density, decreased in both transplantation groups and phosphorylated endothelial nitric-oxide synthase (eNOS) was down-regulated. Portosystemic shunts determined by splenorenal shunt (SRS) flow decreased in both transplantation groups (P=0.037, 0.032). Shunting severity assessed by microsphere distribution method showed consistent results. Compared with sham rats, cirrhotic rats lacked Lachnospiraceae. Both microbiota transplants increased Bifidobacterium. In conclusion, microbiota transplantation in cirrhotic rats reduced portal pressure, alleviated splanchnic hyperdynamic circulation and portosystemic shunts. The main beneficial effects may be focused on portosystemic collaterals-related events, such as hepatic encephalopathy and gastroesophageal variceal hemorrhage. Further clinical investigations are mandatory.