Notes

[Radial mind breaks : Epidemiology, prognosis, treatment method along with outcome].
Predicted adult heights increased significantly from 168.4 ± 3.7 to 173.0 ± 4.2 cm, while oestrogen levels dropped from 33.2 ± 7.4 to 21.6 ± 7.3 pg/mL. Increments in predicted adult height were significantly correlated with trough letrozole concentrations (r = 0.39, P = .01).

Letrozole treatment in Chinese pubertal populations should be further optimized, and more personalized therapies should be developed.
Letrozole treatment in Chinese pubertal populations should be further optimized, and more personalized therapies should be developed.Septoria nodorum blotch (SNB), a disease caused by the necrotrophic fungal pathogen Parastagonospora nodorum, is a threat to wheat (Triticum aestivum) production worldwide. Multiple inverse gene-for-gene interactions involving the recognition of necrotrophic effectors (NEs) by wheat sensitivity genes play major roles in causing SNB. One interaction involves the wheat gene Snn3 and the P. nodorum NE SnTox3. Here, we used a map-based strategy to clone the Snn3-D1 gene from Aegilops tauschii, the D-genome progenitor of common wheat. Snn3-D1 contained protein kinase and major sperm protein domains, both of which were essential for function as confirmed by mutagenesis. As opposed to other characterized interactions in this pathosystem, a compatible Snn3-D1-SnTox3 interaction was light-independent, and Snn3-D1 transcriptional expression was downregulated by light and upregulated by darkness. Snn3-D1 likely emerged in Ae. tauschii due to an approximately 218-kb insertion that occurred along the west bank of the Caspian Sea. The identification of this new class of NE sensitivity genes combined with the previously cloned sensitivity genes demonstrates that P. nodorum can take advantage of diverse host targets to trigger SNB susceptibility in wheat.Defining the pulmonary cell types infected by SARS-CoV-2 and finding ways to prevent subsequent tissue damage are key goals for controlling COVID-19. Recent work establishing a human lung organoid-derived air-liquid interface model permissive to SARS-CoV-2 infection identifies alveolar type II cells as the primary cell type infected, reports an infection-induced interferon response and demonstrates the effectiveness of interferon lambda 1 treatment in dampening lung infection.
Dysferlinopathy is a muscular dystrophy with a highly variable clinical presentation and currently unpredictable progression. This variability and unpredictability presents difficulties for prognostication and clinical trial design. The Jain Clinical Outcomes Study of Dysferlinopathy aims to establish the validity of the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) scale and identify factors that influence the rate of disease progression using NSAD.

We collected a longitudinal series of functional assessments from 187 patients with dysferlinopathy over 3 years. Rasch analysis was used to develop the NSAD, a motor performance scale suitable for ambulant and nonambulant patients. Generalized estimating equations were used to evaluate the impact of patient factors on outcome trajectories.

The NSAD detected significant change in clinical progression over 1 year. The steepest functional decline occurred during the first 10 years after symptom onset, with more rapid decline noted in course and in the short-term for clinical trial preparation. Through further work and validation in this cohort, we anticipate that a disease model incorporating functional performance will allow for more accurate prognosis for patients with dysferlinopathy. ANN NEUROL 2021;89967-978.
Validated scoring tools, such as the Nutritional Risk Index (NRI), can aid clinicians in quantifying the degree of malnourishment in patients prior to an operation. We evaluated the association between NRI and outcomes after heart transplantation.

The United Network for Organ Sharing (UNOS) database was used to identify adult patients (age>18) undergoing heart transplantation between 1987 and 2016. NRI was calculated and categorized into previously established groupings representing severity of malnutrition. Multivariate Cox proportional hazards modeling were used to assess the primary outcome of all-cause mortality.

A total of 25,236 patients were included in the analysis. Most patients (75.4%) were male. Malnourishment was absent (NRI≥100) in 11,022 (44%) patients, while 2,898 (12%) were mildly malnourished (97.5≤NRI<100), 8,685 (34%) were moderately malnourished (83.5≤NRI<97.5), and 2,631 (10%) were severely malnourished (NRI<83.5). Moderate-to-severe malnutrition was associated with increased mortality (HR=1.18, p<.001, 95%CI 1.13-1.24), and post-transplant renal failure requiring dialysis (OR 1.13, p<.001, 95%CI 1.03-1.23).

Malnourishment determined by NRI is independently associated with mortality and post-transplant dialysis after heart transplant. This is the largest study of NRI in heart transplant recipients.
Malnourishment determined by NRI is independently associated with mortality and post-transplant dialysis after heart transplant. This is the largest study of NRI in heart transplant recipients.The Commission on Dental Accreditations states that "graduates must be competent in the use of critical thinking and problem-solving." With this in mind, dental education programs continually strive to enhance and deepen these skills by incorporating effective instructional strategies into the curriculum. To do this, predoctoral dental education has used a variety of techniques including problem-based learning, OSCEs, and standardized patient activities. Another technique, while less popular but potentially more effective if done well, is reflective writing. This study aimed to assess the effect of reflective writing on students' critical thinking skills and learning in dental education programs. Two database searches conducted between 2000 and 2019 resulted in 317 articles after the initial screening. Ultimately, 13 articles met inclusion criteria. The following recurring factors were identified for inclusion in dental education reflective writing initiative reflective writing interventions, reflective writing instructions, writing prompts, evaluation frameworks, and negative perceptions of reflective writing. In answering the key aim of this review, 12 of the 13 studies determined that reflective writing had a positive impact on students' critical thinking, judgment, and/or learning. Key findings included positive effects on student growth in reflection, learning through reflective writing, reflection skills, self-assessment, critical thinking, clinical reasoning, problem solving, and motivation to change after evaluated experiences. The review indicated that dental education programs, which implemented reflective writing as an assessment tool within the curriculum as a means of developing and deepening critical thinking skills and learning were by and large successful in this effort.
This systematic review summarizes results of studies that evaluated the expression of microRNAs (miRs) in prediabetes or type 2 diabetes (T2D).

The information was obtained from PubMed, EMBL-EBI, Wanfang, Trip Database, Lilacs, CINAHL, Human microRNA Disease Database (HMDD) v3.0, and Google. A qualitative synthesis of the results was performed and miRs frequency was graphically represented. From 1893 identified studies, only 55 fulfilled the inclusion criteria. These 55 studies analyzed miRs in T2D, and of them, 13 also described data of prediabetes.

In diabetics, 122 miRs were reported and 35 miRs for prediabetics. However, we identified that five miRs (-122-5p, 144-3p, 210, 375, and -126b) were reported more often in diabetics and four (144-3p, -192, 29a, and -30d) in prediabetics.

Circulating miRs could be used as biomarkers of T2D. However, it is necessary to validate these microRNAs in prospective and multicenter studies with different population subgroups, considering age, gender, and risk factors.
Circulating miRs could be used as biomarkers of T2D. However, it is necessary to validate these microRNAs in prospective and multicenter studies with different population subgroups, considering age, gender, and risk factors.
Two-dimensional speckle-tracking echocardiography (2D-STE) is a novel method that allows the assessment of regional myocardial function. The aim of our study was to use 2D-STE to assess left ventricular deformation in patients with coarctation of the aorta (CoA).

In this prospective study, patients with CoA (n=42) and healthy controls (n=39) were recruited. Children with CoA who visited the outpatient clinic between 2013 and 2014 were included. The data were compared with those obtained from the sex- and age-matched controls.

The mean age of the patients was 5.8±4.5years. Global longitudinal strain based on all three apical views and total global strain values did not appear to be different between the patient and the control groups (P=.59, P=.51, P=.15, P=.38). Hypertension was detected in 14 (33.3%) patients with CoA. There were significant differences between the global longitudinal strain values of the normotensive CoA subgroup and the hypertensive CoA subgroup (P < .05).

In our study, we found that 2D-STE total strain analysis of patients with CoA was not different from comparative healthy controls. However, we determined that 2D-STE parameters were lower in the hypertensive CoA subgroup compared to the normotensive CoA subgroup.
In our study, we found that 2D-STE total strain analysis of patients with CoA was not different from comparative healthy controls. However, we determined that 2D-STE parameters were lower in the hypertensive CoA subgroup compared to the normotensive CoA subgroup.A combination of wildfires and defoliating insect outbreaks play an important role in the natural successional dynamics of North American boreal mixedwood forests, which, in the long term, change the post-disturbance composition and structure of forest stands. After stand-replacing disturbances (mainly wildfires), early successional hardwoods typically dominate the affected areas. Provided enough time following disturbances, the increasing recruitment of mid- to late-successional softwoods as well as the mortality of hardwoods gradually change forest composition from hardwoods to admixtures of hardwood-conifer species and conifer-dominated stands in mid and late successional stages, respectively. Such mixedwoods are abundant across the southern Canadian boreal forest. In boreal Canada, mixedwoods are the most structurally heterogeneous forest ecosystems, are highly productive, and form an important source of timber supply. Here we present the EASTERN BOREAL MIXEDWOODS CANADA data set, which documents the changes in composition and structure of stands originating from eight different wildfires representing a chronosequence of 249 yr since fire in eastern Canada. This data set has been used in several different projects to study and model the influence of natural (e.g., insect outbreaks) and anthropogenic disturbances (e.g., harvesting) on the dynamics of post-fire stands. The data set covers a high range of variability in stand composition and structure, explained by species establishment, dominance, and mixture. It thus constitutes a useful source of information to trace the dynamics of the main boreal tree species of eastern North America, from their establishment to their replacement at different spatial scales (e.g., from stand to landscape level). Please cite this data paper when the data are used in publications. We also request that researchers and teachers inform us of how they are using the data. We are open to collaborate in developing or co-authoring relevant research projects based on this data set.The structure of heterotetrameric sarcosine oxidase (HSO) contains a highly complex system composed of a large cavity and tunnels, which are essential for the reaction and migration of the reactants, products, and intermediates. Previous geometrical analysis using the CAVER program has predicted that there are three possible tunnels, T1, T2, and T3, for the exit pathway of the iminium intermediate, 5-oxazolidinone (5-OXA), of the enzyme reaction. Previous molecular dynamics (MD) simulation of HSO has identified the regions containing the water channels from the density distribution of water. The simulation indicated that tunnel T3 is the most probable exit pathway of 5-OXA. In the present study, the potential of mean force (PMF) for the transport of 5-OXA through tunnels T1, T2, and T3 was calculated using umbrella sampling (US) MD simulations and the weighted histogram analysis method. The PMF profiles for the three tunnels support the notion that tunnel T3 is the exit pathway of 5-OXA, and that 5-OXA tends to stay at the middle of the tunnel. The maximum errors of the calculated PMF for the predicted exit pathway, tunnel T3, were estimated by repeating the US simulations using different sets of initial positions. The PMF profile was also calculated for the transport of glycine within T3. The PMF profiles from the US simulations were in good agreement with the previous predictions that 5-OXA escape through tunnel T3 and how glycine is released to the outside of HSO was discussed.
Epidermal T cells play a central role in immune surveillance and in inflammatory skin diseases. Major differences in the epidermal T cell composition are found between adult humans and antigen-inexperienced laboratory mice. Whether this is due to inborn species differences, to different environmental exposures, or a combination of the two is a matter of debate.

To investigate the role of age and exposure to antigens on epidermal T cell subsets in human and mouse skin.

We isolated T cells from the epidermis from 19 infants and 26 adults, and determined the frequency of CD4
and CD8
αβ T cells and γδ T cells by flow cytometry. In addition, we determined the epidermal T cell composition in antigen-inexperienced and antigen-experienced mice.

We found that humans are born with very few epidermal T cells. The number increases and the composition changes with age. In antigen-inexperienced mice, the epidermal T cell composition is unaffected by age, but it is dramatically affected by antigen exposure.

Taken together, we show that antigen exposure, as opposed to age, is the major factor determining the composition of epidermal T cells, suggesting that the skin of antigen-experienced mice better reflects the immunological conditions in human skin.
Taken together, we show that antigen exposure, as opposed to age, is the major factor determining the composition of epidermal T cells, suggesting that the skin of antigen-experienced mice better reflects the immunological conditions in human skin.
Elucidation of the antiproliferative efficacy and mechanism of action of a design-optimized noscapine analog, N-4-CN.

Cell viability was studied using an MTT assay. The drug-tubulin interactions were investigated using spectrofluorometry. The architectural defects, hyper stabilization, and recovery competence of cellular microtubules were studied using immunofluorescence microscopy. DCF-DH and rhodamine 123 were used as probes to to examine the levels of reactive oxygen species and the loss of mitochondrial membrane potential, respectively. Flow cytometry revealed the cell cycle progression pattern of the drug-treated cells.

Among the cell lines tested, N-4-CN showed the strongest inhibition of the viability of the triple-negative breast cancer (TNBC) cell line MDA-MB-231(IC
, 2.7±0.1µmol/L) and weakest inhibition of the noncancerous epithelial cell line, VERO (IC
, 60.2±3µmol/L). It perturbed tertiary structure of tubulin and stabilized colchicine binding to the protein. In cells, N-4-CN hyperstabilized the microtubules, and prevented the recovery of cold-depolymerized microtubules. Its multitude of effects on tubulin and microtubules facilitated cell cycle arrest and subsequent cell death that were complemented by elevated levels of reactive oxygen species (ROS).

Owing to its ability to perturb a well-defined cancer drug target, tubulin, and to promote ROS-facilitated apoptosis, N-4-CN could be investigated further as a potential therapeutic against many neoplasms, including TNBC.
Owing to its ability to perturb a well-defined cancer drug target, tubulin, and to promote ROS-facilitated apoptosis, N-4-CN could be investigated further as a potential therapeutic against many neoplasms, including TNBC.
Patch testing is the gold standard for identifying culprit allergens in allergic contact dermatitis; however, it is laborious and positive reactions are difficult to quantitate. Development of complementary in vitro tests is, therefore, of great importance.

This study aimed to improve the in vitro lymphocyte proliferation test (LPT) to detect allergic responses to nickel (Ni), cobalt (Co), and chromium (Cr).

Twenty-one metal allergic patients with a positive patch test to Ni (n=16), Co (n=8), and Cr (n=3) and 13 controls were included. All were tested by a flow cytometric LPT.

Metal-reactive cells were identified as T helper (Th) cells with high expression of the memory marker CD45RO. Skin-homing (cutaneous lymphocyte-associated antigen positive [CLA+]) Ni-reactive memory Th (Th

) cells identified individuals with a positive patch test for Ni with 100% sensitivity (95% confidence interval [CI] 81%-100%) and 92% specificity (95% CI 67%-100%). Moreover, Co-specific Th

cells expressing CCR6 identified patients with a positive patch test for Co with 63% sensitivity (95% CI 31%-86%) and 100% specificity (95% CI 77%-100%). In Cr allergic individuals, Cr-reactive Th

cells tended to increased CLA and CCR6 expression.

Metal-reactive Th cells with high expression of CD45RO and coexpression of CLA and CCR6 improved the LPT, making it an attractive supplement to the patch test.
Metal-reactive Th cells with high expression of CD45RO and coexpression of CLA and CCR6 improved the LPT, making it an attractive supplement to the patch test.The forebrain includes the cerebral cortex, the thalamus, and the striatum and globus pallidus (GP) in the subpallium. The formation of these structures and their interconnections by specific axonal tracts take place in a precise and orchestrated time and spatial-dependent manner during development. However, the knowledge of the molecular and cellular mechanisms that are involved is rather limited. Moreover, while many extracellular cues and specific receptors have been shown to play a role in different aspects of nervous system development, including neuron migration and axon guidance, examples of intracellular signaling effectors involved in these processes are sparse. In the present work, we have shown that the atypical RhoGTPase, Rnd3, is expressed very early during brain development and keeps a dynamic expression in several brain regions including the cortex, the thalamus, and the subpallium. By using a gene-trap allele (Rnd3gt ) and immunological techniques, we have shown that Rnd3gt/gt embryos display severe defects in striatal and thalamocortical axonal projections (SAs and TCAs, respectively) and defects in GP formation already at early stages. Surprisingly, the corridor, an important intermediate target for TCAs is still present in these mutants. Mechanistically, a conditional genetic deletion approach revealed that Rnd3 is primarily required for the normal development of Medial Ganglionic Eminence-derived structures, such as the GP, and therefore acts non-cell autonomously in SAs and TCAs. In conclusion, we have demonstrated the important role of Rnd3 as an early regulator of subpallium development in vivo and revealed new insights about SAs and TCAs development.
To evaluate the diagnostic value of still images of needle arthroscopy (SNAR), still images of traditional arthroscopy (STAR), and computed tomography (CT) to diagnose medial coronoid process (MCP) pathology.

Prospective clinical trial.

Dogs (n = 17) presented for evaluation of elbow dysplasia.

For each case, two SNAR and STAR images of the MCP were reviewed independently and in random order by three board-certified surgeons. Computed tomographic images were reviewed by one board-certified radiologist. Reviewers were blinded to surgical and clinical findings. Surgical findings from real-time TAR with palpation were used as the gold standard. Receiver operating characteristic (ROC) curves and concordance statistics tests for the diagnostic accuracy of MCP fissure, MCP fragment, medial compartment condition, and cartilage score were calculated.

Images of 27 elbows joints were reviewed. For MCP fissure detection, areas under the ROC curves for CT (0.84), STAR (0.73), and SNAR (0.57) did not differ. For the detection of MCP fragment, STAR had a larger area under the ROC curve (0.93) compared with SNAR (0.74, P = .015) and CT (0.54, P < .001). Still images of TAR and SNAR had comparable concordance for cartilage score (0.80 and 0.77, respectively) and medial compartment pathology (0.80 and 0.73, respectively).

Still images of NAR, STAR, and CT had similar diagnostic value to identify MCP fissures. Still images of TAR was superior to SNAR and CT to identify MCP fragments.

The diagnostic accuracy of SNAR varied on the basis of the coronoid lesion being evaluated.
The diagnostic accuracy of SNAR varied on the basis of the coronoid lesion being evaluated.Targeted anticancer therapy is being used with greater frequency and dermatologic toxicities are among the most frequent adverse events of these drugs. However, histopathological features of these adverse events are not yet well characterized. We present two cases of clinically different cutaneous toxicities on two patients with hematologic neoplasia. They were treated with different drugs and in both cases medications shared inhibition of PI3K as mechanism of action. The skin biopsy specimen showed endothelial cell atypia with large nuclei and mitotic figures. To the best of our knowledge, no other cases with these striking histopathologic findings have been reported with PI3K inhibitors or other anticancer targeted therapy.Polymer composite films containing fillers comprising quasi-1D van der Waals materials, specifically transition metal trichalcogenides with 1D structural motifs that enable their exfoliation into bundles of atomic threads, are reported. These nanostructures are characterized by extremely large aspect ratios of up to ≈106 . The polymer composites with low loadings of quasi-1D TaSe3 fillers ( less then 3 vol%) reveal excellent electromagnetic interference shielding in the X-band GHz and extremely high frequency sub-THz frequency ranges, while remaining DC electrically insulating. The unique electromagnetic shielding characteristics of these films are attributed to effective coupling of the electromagnetic waves to the high-aspect-ratio electrically conductive TaSe3 atomic-thread bundles even when the filler concentration is below the electrical percolation threshold. These novel films are promising for high-frequency communication technologies, which require electromagnetic shielding films that are flexible, lightweight, corrosion resistant, inexpensive, and electrically insulating.Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes a crucial step in the biosynthesis of DNA and RNA, and it has been exploited as a promising target for antimicrobial therapy. The present study discusses the development and synthesis of a series of sulfonyl-α-l-amino acids coupled with the anisamide scaffold and evaluates their activities as anti-Helicobacter pylori and IMPDH inhibitors. Twenty derivatives were synthesized and their structures were established by high-resolution mass spectrometry and 1 H and 13 C nuclear magnetic resonance measurements. Four compounds (6, 10, 11, and 21) were found to be the most potent and selective molecules in the series with minimum inhibitory concentration (MIC) values  17.17 µM, which makes sure that their selectivity is toward HpIMPDH and reverse to that of amoxicillin and clarithromycin. Also, the synergistic antibacterial activity of compounds 6, 10, amoxicillin, and clarithromycin was investigated in vitro. The combination of amoxicillin/compound 6 (21 by weight) exhibited a significant antibacterial activity against H. pylori, with MIC = 0.12 µg/ml. The molecular docking study and ADMET analysis of the most active compounds were used to elucidate the mode-of-action mechanism.
Poor communication is a barrier to care for people with hearing loss. We assessed the feasibility and potential benefit of providing a simple hearing assistance device during an emergency department (ED) visit, for people who reported difficulty hearing.

Randomized controlled pilot study.

The ED of New York Harbor Manhattan Veterans Administration Medical Center.

One hundred and thirty-three Veterans aged 60 and older, presenting to the ED, likely to be discharged to home, who either (1) said that they had difficulty hearing, or (2) scored 10 or greater (range 0-40) on the Hearing Handicap Inventory-Survey (HHI-S).

Subjects were randomized (11), and intervention subjects received a personal amplifier (PA; Williams Sound Pocketalker 2.0) for use during their ED visit.

Three survey instruments (1) six-item Hearing and Understanding Questionnaire (HUQ); (2) three-item Care Transitions Measure; and (3) three-item Patient Understanding of Discharge Information. Post-ED visit phone calls to assess ED rekely to return to the ED within 3 days. PAs may be an important adjunct to older patient ED care but require validation in a larger more definitive randomized controlled trial.
Nonalcoholic fatty liver disease (NAFLD), especially the nonalcoholic steatohepatitis (NASH), have become a major cause of liver transplantation and liver-associated death. NASH is the hepatic manifestation of metabolic syndrome and is characterized by hepatic steatosis, inflammation, hepatocellular injury and different degrees of fibrosis. However, there is no FDA-approved medication to treat this devastating disease. Therapeutic activators of the AMP-Activated Protein Kinase (AMPK) have been proposed as a potential treatment for metabolic diseases such as NASH. Cordycepin, a natural product isolated from the traditional Chinese medicine Cordyceps militaris, has recently emerged as a promising drug candidate for metabolic diseases.

We evaluated the effects of cordycepin on lipid storage in hepatocytes, inflammation, and fibrosis development in mice with NASH. Cordycepin attenuated lipid accumulation, inflammation and lipotoxicity in hepatocytes subjected to metabolic stress. In addition, cordycepin treatess through activation of the AMPK signaling pathway. Cordycepin might be a novel AMPK activator that can be used for the treatment of NASH.Melanins are a diverse group of dark pigments with similar properties. In fungi, the most studied is the dihydroxynaphtalene (DHN)-melanin, present in several species including all the chromoblastomycosis agents, a chronic, disabling, and recalcitrant subcutaneous mycosis. It is synthesized in a pathway known as the pentaketide pathway, which has the agrochemical tricyclazole as an inhibitor, widely used in in vitro studies because it does not prevent the growth of fungi. There are different methodologies for qualitative and quantitative analyses of DHN-melanin, which made it possible to discover its important structural and antioxidant functions, with melanin acting as a protective factor against the host's immune system. Also, it can interact with some of the main antifungals of medical interest, reducing its activity and the susceptibility of fungi to these agents. This review aims to discuss the aspects of DHN-melanin, focusing on chromoblastomycosis, bringing the main findings of the published scientific studies, and highlighting the need for further research to understand this important fungal pathogenicity and a virulence factor.Rapid increases in minimum night temperature than in maximum day temperature is predicted to continue, posing significant challenges to crop productivity. Rice and wheat are two major staples that are sensitive to high night-temperature (HNT) stress. This review aims to (i) systematically compare the grain yield responses of rice and wheat exposed to HNT stress across scales, and (ii) understand the physiological and biochemical responses that affect grain yield and quality. To achieve this, we combined a synthesis of current literature on HNT effects on rice and wheat with information from a series of independent experiments we conducted across scales, using a common set of genetic materials to avoid confounding our findings with differences in genetic background. In addition, we explored HNT-induced alterations in physiological mechanisms including carbon balance, source-sink metabolite changes and reactive oxygen species. Impacts of HNT on grain developmental dynamics focused on grain-filling duration, post-flowering senescence, changes in grain starch and protein composition, starch metabolism enzymes and chalk formation in rice grains are summarized. Finally, we highlight the need for high-throughput field-based phenotyping facilities for improved assessment of large-diversity panels and mapping populations to aid breeding for increased resilience to HNT in crops.Because long-term leachate penetration through a hydraulic barrier is unavoidable, active-passive liners are widely used to mitigate the migration of potential contaminants. Geopolymerization represents a viable method for metals removal, which simultaneously improves the properties of local clay to compensate for the lack of suitable soil in the design of active-passive liners. This study investigated how clay-fly ash geopolymers enhance the sorption of divalent lead [Pb(II)] and divalent zinc [Zn(II)] from leachate compared with an untreated clay. Two clay-fly ash geopolymers were synthesized from the mixtures containing 50 and 60% fly ash to the total solid mass and then activated by 10 M NaOH solutions. The influence of Na/fly ash ratios and activator content was also examined. The results indicate that a fly ash-based geopolymer could be a simple solution to increase the sorption capacity of local clay. A lower ratio of Na/fly ash and activator content, resulting in a higher porosity, led to a better performance for metal removal. According to the results of sorption isotherms and batch experiments, Pb(II) and Zn(II) exhibit different sorption behaviors affected by the compositions of synthesized clay-fly ash geopolymers, which could be adjusted to reach a proper sorption capacity. The results of the kinetic study also show that the heterogeneous matrix of the clay-fly ash geopolymers with different porosities led to mutual cooperation between reaction and diffusion-controlled steps for metal removal.Tolerating or condoning practices that one finds objectionable is typically considered a positive way to negotiate intergroup differences. However, being the target of tolerance might harm well-being, which we examined in three studies (a survey and two experiments) among a total of 1,054 members of various racial/ethnic minority groups in the United States. In Study 1, we found that perceiving oneself to be tolerated on the basis of one's ethnic group membership was associated with more negative well-being. In Study 2, we found that bringing to mind experiences of being tolerated results in less positive and more negative affect than thinking about experiences of acceptance, but more positive and less negative outcomes than thinking about overt discrimination experiences. In Study 3, we replicated the results of Study 2 while demonstrating that threat to social identity needs mediates the tolerance-well-being link. These results suggest that being tolerated is related to minority targets' well-being in ways that are intermediate between being treated with outright discrimination and full acceptance, but that being tolerated follows a pattern closer to discrimination.
The durability of improved xerostomia with intensity-modulated radiotherapy (IMRT) in patients with early stage nasopharyngeal carcinoma (NPC) is uncertain. We conducted a long-term prospective assessment of participants treated with IMRT or two-dimensional radiotherapy (2DRT) in a prior randomized study.

Parent study participants (IMRT, n = 28; 2DRT, n = 28) who were free of second malignancy or recurrence were eligible. Long-term radiotherapy-related toxicities were graded according to the Radiation Therapy Oncology Group (RTOG) criteria. Long-term patient-reported outcomes were assessed by the six-item xerostomia (XQ) and two European Organisation for Research and Treatment of Cancer (EORTC) questionnaires (QLQ-C30, QLQ-H&N35). Overall survival (OS), locoregional relapse-free survival (LRFS), distant relapse-free survival (DRFS), and the rate of symptomatic late complications (SLCs) were estimated for the entire cohort (n = 56).

Totally, 21 (IMRT, n = 10; 2DRT, n = 11) patients gave consent and were assessed for an overall median follow-up of 15.5 years. There was significantly less RTOG ≥grade 2 xerostomia with IMRT versus 2DRT (20% vs. 90%; p = 0.001), but no significant difference in XQ scores. Patients in the IMRT arm reported lower mean scores for the "dry mouth" domain of EORTC QLQ-H&N35 (p = 0.02) and showed trends toward better 15-year OS (81.5% vs. 53.8%, p = 0.06), LRFS (70.6% vs. 53.8%, p = 0.38), and DRFS (81.5% vs. 53.8%, p = 0.07). SLCs were more frequent in the 2DRT arm.

The parotid-sparing effect of IMRT in NPC treatment is durable, with significantly less physician- and patient-scored xerostomia at 15 years. IMRT results in better long-term survival and fewer SLCs.
The parotid-sparing effect of IMRT in NPC treatment is durable, with significantly less physician- and patient-scored xerostomia at 15 years. IMRT results in better long-term survival and fewer SLCs.
Many parents bereaved of a stillborn baby spend time with the child. In this time frame, different acts with the child in focus may occur. Some parents invite others to see the child too. Parents who suffer the loss of a newborn are vulnerable, and understanding acts and practices surrounding the dead newborn is important knowledge for caretakers.

This article aims to enlighten the amount of time Danish parents spend with their stillborn in hospital settings that encourage this practice. Furthermore, it aims to transcend the mere quantitative numbers through a theoretical approach that frames the analysis and discussion of possible layers of meaning imbedded in time spent with a dead newborn.

Data from a Danish cohort of bereaved parents were collected using web-based questionnaires. These numbers were successively interpreted through an anthropological lens within the perspective of transition and ritualisation. Knowledge from existing empirical literature was also fused.

Danish parents spend hours o death. In liminal space during the transition, healthcare professionals act as ritual experts, supporting parents and their relatives to ascribe social status to the dead body of the child through ritualised acts. Instead of only thinking of this period as 'memory-making', we suggest regarding it as a time of ontological clarification as well.
The oxygen cost of high-intensity exercise at power outputs above an individual's lactate threshold (LT) is greater than would be predicted by the linear oxygen consumption-power relationship observed below the LT. However, whether these augmentations are caused by an increased ATP cost of force generation (ATP
) or an increased oxygen cost of ATP synthesis is unclear. We used
P-MRS to measure changes in cytosolic [ADP] (intramyocellular marker of oxidative metabolism), oxidative ATP synthesis (ATP
) and ATP
during a 6-stage, stepwise knee extension protocol. ATP
was unchanged across stages. The relationship between [ADP] and muscle power output was augmented at workloads above the pH threshold (pH
; proxy for LT), whereas increases in ATP
were attenuated. These results suggest the greater oxygen cost of contractions at workloads beyond the pH
is not caused by mechanisms that increase ATP
, but rather mechanisms that alter intrinsic mitochondrial function or capacity.

Increases in skele suggest that greater oxidative metabolism at workloads beyond the pHT is caused by mechanisms that affect intrinsic mitochondrial function or capacity, such as alterations in substrate selection or electron entry into the electron transport chain, temperature-mediated changes in mitochondrial permeability to protons, or stimulation of mitochondrial uncoupling by reactive oxygen species generation.Treatment planning in high dose-rate brachytherapy has traditionally been conducted with manual forward planning, but inverse planning is today increasingly used in clinical practice. There is a large variety of proposed optimization models and algorithms to model and solve the treatment planning problem. Two major parts of inverse treatment planning for which mathematical optimization can be used are the decisions about catheter placement and dwell time distributions. Both these problems as well as integrated approaches are included in this review. The proposed models include linear penalty models, dose-volume models, mean-tail dose models, quadratic penalty models, radiobiological models, and multiobjective models. The aim of this survey is twofold (i) to give a broad overview over mathematical optimization models used for treatment planning of brachytherapy and (ii) to provide mathematical analyses and comparisons between models. New technologies for brachytherapy treatments and methods for treatment planning are also discussed. Of particular interest for future research is a thorough comparison between optimization models and algorithms on the same dataset, and clinical validation of proposed optimization approaches with respect to patient outcome.
In this study, we aimed to evaluate diaphragmatic dysfunction (DD) by using a practical approach in patients with amyotrophic lateral sclerosis (ALS) at the first visit to a chest diseases outpatient clinic.

Patients with ALS seen in our outpatient clinic for the past 5 y and followed up for at least 1 y, were retrospectively evaluated. Having at least one of the following three criteria was accepted as DD (a) paradoxical abdominal movement (PAM), (b) sitting-supine forced vital capacity (FVC) difference ≥ 20%, (c) sitting-supine arterial oxygen saturation measured by pulse oximetry (SpO
) difference ≥ 4%. Respiratory symptoms, arterial blood gas analysis, sleep studies, noninvasive mechanical ventilation use, and mortality were recorded.

Five-hundred patients with ALS were included (female/male 220/280, age 58.9 ± 11.3 y). Of the patients, 22.8% had daytime hypercapnia. DD was observed in 55% of the patients (PAM in 112, sitting-supine FVC difference ≥ 20% in 50, and sitting-supine SpO
difference ≥ 4% in 113 patients). Of the patients with DD, 31.6% (n = 87) had no respiratory symptoms, 46.4% had FVC > 70% and 33.5% had FVC <50%. Nocturnal hypoxemia (sleep time spent with SpO
 < 90% ≥30%) was present in 59.7%, and all patients with nocturnal hypoxemia had DD. Obstructive sleep apnea (8 severe, 14 moderate, 39 mild) was detected in 55% of the patients with polysomnography (n = 61) or polygraphy (n = 50). During follow-up, 52.2% of the patients died. Mean survival time was shorter in patients with DD (P < .001).

Paradoxical abdomimal movement (PAM), sitting-supine SpO
difference ≥ 4% and sitting-supine FVC difference ≥ 20% are indicators of DD, which should be routinely evaluated at every outpatient visit.
Paradoxical abdomimal movement (PAM), sitting-supine SpO2 difference ≥ 4% and sitting-supine FVC difference ≥ 20% are indicators of DD, which should be routinely evaluated at every outpatient visit.Multidrug-resistant bacteria are causing a serious global health crisis. A dramatic decline in antibiotic discovery and development investment by pharmaceutical industry over the last decades has slowed the adoption of new technologies. It is imperative that we create new mechanistic insights based on latest technologies, and use translational strategies to optimize patient therapy. Although drug development has relied on minimal inhibitory concentration testing and established in vitro and mouse infection models, the limited understanding of outer membrane permeability in Gram-negative bacteria presents major challenges. Our team has developed a platform using the latest technologies to characterize target site penetration and receptor binding in intact bacteria that inform translational modeling and guide new discovery. Enhanced assays can quantify the outer membrane permeability of β-lactam antibiotics and β-lactamase inhibitors using multiplex liquid chromatography tandem mass spectrometry. While β-lactam antibiotics are known to bind to multiple different penicillin-binding proteins (PBPs), their binding profiles are almost always studied in lysed bacteria. Novel assays for PBP binding in the periplasm of intact bacteria were developed and proteins identified via proteomics. To characterize bacterial morphology changes in response to PBP binding, high-throughput flow cytometry and time-lapse confocal microscopy with fluorescent probes provide unprecedented mechanistic insights. Moreover, novel assays to quantify cytosolic receptor binding and intracellular drug concentrations inform target site occupancy. These mechanistic data are integrated by quantitative and systems pharmacology modeling to maximize bacterial killing and minimize resistance in in vitro and mouse infection models. This translational approach holds promise to identify antibiotic combination dosing strategies for patients with serious infections.
Establishing the diagnosis of Huntington's disease (HD) involves molecular genetic testing and estimation of the number of CAG repeats.

We report a 42-year-old patient with clinical phenotype suggestive of HD, who was repeatedly negative on genetic testing for HD at a reference laboratory. He had positive history of similar symptoms in his father, but not in other family members. During a 2-year follow-up his symptoms slowly deteriorated (videos attached). The family history was misleading, as we discovered that patient's father was adopted as infant. Having excluded HD-like disorders and other causes of the symptoms we hypothesized that the primer could not bind to the mutated allele.

The PCR reaction with primers HD1 and Hu3 revealed homozygosity of the other adjacent microsatellite tract consisting of the CCG repeats. The newly designed set of primers, located outside of the CAG tract (HD6extF, HD7extR) was used and enabled amplification of the mutant allele and detection of the abnormal range of CAG repeats.

As application of the novel primers led to the diagnosis of HD in other 5 patients previously tested negative, we propose their incorporation into routine genetic testing in patients suspected of HD displaying homoallelism in the standard protocol.
As application of the novel primers led to the diagnosis of HD in other 5 patients previously tested negative, we propose their incorporation into routine genetic testing in patients suspected of HD displaying homoallelism in the standard protocol.Estimation and inference are two key components toward the solution of any statistical problem; however, the inferential issues of statistical assessment of agreement among two or more raters have not been well developed as compared to the development of estimation procedures in this area. The fundamental reason for this gap is the complex expression of the concordance correlation coefficient (CCC) that is frequently used in assessing agreement among raters. Large sample-based statistical tests for CCC often fail to produce desired results for small samples. Hence, inferential procedures for small samples are urgently needed to evaluate agreement between raters. We argue that hypothesis testing of CCC has little value in practice due to the absence of a gold standard of agreement. In this article, we construct the generalized confidence interval (GCI) for CCC utilizing a bivariate normal distribution of measurements, and also develop a large sample-based confidence interval (LSCI). We establish satisfactory performance of GCI by providing the desired coverage probability (CP) via simulation. Results of GCI and LSCI are illustrated and compared with a data set of a recent study performed at U.S. Department of Veterans Affairs, Hines.
Novel solutions are needed for expediting margin assessment to guide basal cell carcinoma (BCC) surgeries. Ex vivo fluorescence confocal microscopy (FCM) is starting to be used in freshly excised surgical specimens to examine BCC margins in real time. Training and educational process are needed for this novel technology to be implemented into clinic.

To test a training and reading process, and measure diagnostic accuracy of clinicians with varying expertise level in reading ex vivo FCM images.

An international three-center study was designed for training and reading to assess BCC surgical margins and residual subtypes. Each center included a lead dermatologic/Mohs surgeon (clinical developer of FCM) and three additional readers (dermatologist, dermatopathologist, dermatologic/Mohs surgeon), who use confocal in clinical practice. Testing was conducted on 30 samples.

Overall, the readers achieved 90% average sensitivity, 78% average specificity in detecting residual BCC margins, showing high and consistent diagnostic reading accuracy. Those with expertise in dermatologic surgery and dermatopathology showed the strongest potential for learning to assess FCM images.

Small dataset, variability in mosaic quality between centers.

Suggested process is feasible and effective. This process is proposed for wider implementation to facilitate wider adoption of FCM to potentially expedite BCC margin assessment to guide surgery in real time.
Suggested process is feasible and effective. This process is proposed for wider implementation to facilitate wider adoption of FCM to potentially expedite BCC margin assessment to guide surgery in real time.Protein stability is subject to environmental perturbations such as pressure and crowding, as well as sticking to other macromolecules and quinary structure. Thus, the environment inside and outside the cell plays a key role in how proteins fold, interact, and function on the scale from a few molecules to macroscopic ensembles. This review discusses three aspects of protein phase diagrams first, the relevance of phase diagrams to protein folding and function in vitro and in cells; next, how the evolution of protein surfaces impacts on interaction phase diagrams; and finally, how phase separation plays a role on much larger length-scales than individual proteins or oligomers, when liquid phase-separated regions form to assist protein function and cell homeostasis.
Antifibrotic therapy remains an unmet medical need in human chronic liver disease. We report the antifibrotic properties of cytoglobin (CYGB), a respiratory protein expressed in hepatic stellate cells (HSCs), the main cell type involved in liver fibrosis.

Cygb-deficient mice that had bile duct ligation-induced liver cholestasis or choline-deficient amino acid-defined diet-induced steatohepatitis significantly exacerbated liver damage, fibrosis, and reactive oxygen species (ROS) formation. All of these manifestations were attenuated in Cygb-overexpressing mice. We produced hexa histidine-tagged recombinant human CYGB (His-CYGB), traced its biodistribution, and assessed its function in HSCs or in mice with advanced liver cirrhosis using thioacetamide (TAA) or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). In cultured HSCs, extracellular His-CYGB was endocytosed and accumulated in endosomes through a clathrin-mediated pathway. His-CYGB significantly impeded ROS formation spontaneously or in the presence of
His-CYGB could have antifibrotic clinical applications for human chronic liver diseases.Transposable elements exist widely throughout plant genomes and play important roles in plant evolution. Auxin is an important regulator that is traditionally associated with root development and drought stress adaptation. The DEEPER ROOTING 1 (DRO1) gene is a key component of rice drought avoidance. Here, we identified a transposon that acts as an autonomous auxin-responsive promoter and its presence at specific genome positions conveys physiological adaptations related to drought avoidance. Rice varieties with a high and auxin-mediated transcription of DRO1 in the root tip show deeper and longer root phenotypes and are thus better adapted to drought. The INDITTO2 transposon contains an auxin response element and displays auxin-responsive promoter activity; it is thus able to convey auxin regulation of transcription to genes in its proximity. In the rice Acuce, which displays DRO1-mediated drought adaptation, the INDITTO2 transposon was found to be inserted at the promoter region of the DRO1 locus. Transgenesis-based insertion of the INDITTO2 transposon into the DRO1 promoter of the non-adapted rice variety Nipponbare was sufficient to promote its drought avoidance. Our data identify an example of how transposons can act as promoters and convey hormonal regulation to nearby loci, improving plant fitness in response to different abiotic stresses.
Meta-analytic studies show that the benefits of the growth mindset on academic achievement are heterogenous. Past studies have explored how individual characteristics and proximal environmental factors could explain these variations, but the role of the broader sociocultural environment has seldom been explored.

We investigated society-level social axioms to explain variations in growth mindset effects on achievement across cultures. We hypothesized that three society-level social axioms (social complexity, fate control, and reward for application) imply social norms that would either support or obstruct the growth mindset effect.

We conducted multilevel SEM with random slopes using data from 273,074 students nested within 39 countries/territories.

We found weaker growth mindset effects in societies with stronger social complexity beliefs; societies believing that there are multiple solutions to problems have social norms that obstruct the growth mindset effects on achievement. No moderating effects were found with other social axioms.

Relevant cultural-level normative beliefs should be considered to better assess the relevance of the growth mindset construct.
Relevant cultural-level normative beliefs should be considered to better assess the relevance of the growth mindset construct.
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