Pearsonalford1485

Although there were no significant differences in changes in UPDRS part I, III, or IV between the groups after ZNS treatment, the tremor group had significant improvements in PDSS-2 at 3months and BDI-II at 1, 2 and 3months compared with the nontremor group.

We showed the beneficial effects of ZNS on motor symptoms and sleep problems in levodopa-treated PD patients with motor fluctuation. ZNS may be more effective for several nonmotor symptoms in PD patients with tremor compared with those without tremor.

We showed the beneficial effects of ZNS on motor symptoms and sleep problems in levodopa-treated PD patients with motor fluctuation. ZNS may be more effective for several nonmotor symptoms in PD patients with tremor compared with those without tremor.Platelets mediate key biological processes, including hemostasis, immunity, and inflammation. Although platelets are often treated as a homogeneous cell population, they are known to be heterogeneous in size, age, surface receptor expression, and response to agonist stimulation, raising the possibility that distinct platelet subsets perform specialized functions and that such subsets may be altered in disease settings. Attempts to identify platelet subsets by flow cytometry have had limited success due in part to limits on the number of probes that can be used at the same time and due to the challenges of compensating for probes that have large spectral overlap. We recently reported a method to identify platelet subsets by mass cytometry using a panel of 14 metal-tagged antibodies directed at platelet surface markers. Here, we describe the technical considerations and best practices for platelet sample preparation, processing, and analysis by mass cytometry. Specifically, we show that anticoagulant choice alters platelet phenotype and function and that antibody cocktail storage and sample processing are critical for reproducibility. Additionally, we optimize sample density and instrument setup for maximal platelet transmission. Lastly, we demonstrate the importance of panel design and compensation and the use of clustering and dimension reduction to map platelet heterogeneity across resting and stimulated samples.SOX9, a transcription factor, is expressed in the undifferentiated XX and XY gonads. SRY induces significant upregulation of SOX9 expression in XY gonads. Loss-of-function SOX9 variants cause testicular dysgenesis in 46,XY patients, while duplication of the total gene or the upstream regulatory region results in testicular development in 46,XX patients. However, gain-of-function (GoF) SOX9 variants have not been reported previously. We report the case of a 16-year-old female patient with a 46,XX karyotype who had masculinized external genitalia and unilateral ovotestis. Next-generation sequencing-based genetic screening for disorders of sex development led to the identification of a novel SOX9 variant (p.Glu50Lys), transmitted from the phenotypically normal father. Expression analysis showed that E50K-SOX9 enhanced transactivation of the luciferase reporter containing the testis enhancer sequence core element compared with that containing the wildtype-SOX9. This GoF activity was not observed in the luciferase reporter containing Amh, the gene for anti-Müllerian hormone. We genetically engineered female mice (Sox9E50K/E50K ), and they showed no abnormalities in the external genitalia or ovaries. In conclusion, a novel SOX9 variant with a promoter-specific GoF activity was identified in vitro; however, the disease phenotype was not recapitulated by the mouse model. At present, the association between the GoF SOX9 variant and the ovotestis phenotype remains unclear. Future studies are needed to verify the possible association.For patients with angiitis-induced critical limb ischemia (AICLI), cell transplantation, such as purified CD34+ cells (PCCs) and peripheral blood mononuclear cells (PBMNCs), is gradually being used as a promising treatment. This was the first randomized single-blinded noninferiority trial (number NCT02089828) specifically designed to evaluate the therapeutic efficacies of the transplantation of PCCs vs those of PBMNCs for the treatment of AICLI. We aimed to compare the mid-term safety and efficacy between the two groups and determine their respective advantages. From April 2014 to September 2019, 50 patients with AICLI were equally allocated to the two groups, except for 1 lost patient, 1 amputee, and 1 patient who died of heart disease. The other 47 patients completed the 36-month follow-up. The endpoints were as follows major amputation-free survival and total amputation-free survival at 6 months, which were 96.0% and 84.0% in the PBMNCs group and 96.0% and 72.0% in the PCCs group, respectively. These rates remained stable at 12, 24, and 36 months. The PCCs group had a significant higher probability of rest pain relief than the PBMNCs group, whereas earlier significant improvements in the Rutherford classification were observed in the PBMNCs group. Accordingly, PCCs would be preferred for patients with significant pain, whereas PBMNCs may be a good option for patients with two or more critically ischemic limbs. Concerning cost-effectiveness, PCCs are not more cost-effective than PBMNCs. These outcomes require verification from long-term trials involving larger numbers of patients.Advanced paternal age can have deleterious effects on various traits in the next generation. Here, we establish a paternal-aging model in mice to understand the molecular mechanisms of transgenerational epigenetics. Whole-genome target DNA methylome analyses of sperm from aged mice reveal more hypo-methylated genomic regions enriched in REST/NRSF binding motifs. Gene set enrichment analyses also reveal the upregulation of REST/NRSF target genes in the forebrain of embryos from aged fathers. Offspring derived from young mice administrated with a DNA de-methylation drug phenocopy the abnormal vocal communication of pups derived from aged fathers. In conclusion, hypo-methylation of sperm DNA can be a key molecular feature modulating neurodevelopmental programs in offspring by causing fluctuations in the expression of REST/NRSF target genes.

The increasing evidence of SARS-CoV-2 impact on the central nervous system (CNS) raises key questions on its impact for risk of later life cognitive decline, Alzheimer's disease (AD), and other dementia.

The Alzheimer's Association and representatives from more than 30 countries-with technical guidance from the World Health Organization-have formed an international consortium to study the short-and long-term consequences of SARS-CoV-2 on the CNS-including the underlying biology that may contribute to AD and other dementias. This consortium will link teams from around the world covering more than 22 million COVID-19 cases to enroll two groups of individuals including people with disease, to be evaluated for follow-up evaluations at 6, 9, and 18 months, and people who are already enrolled in existing international research studies to add additional measures and markers of their underlying biology.

The increasing evidence and understanding of SARS-CoV-2's impact on the CNS raises key questions on the impact for risk of later life cognitive decline, AD, and other dementia. This program of studies aims to better understand the long-term consequences that may impact the brain, cognition, and functioning-including the underlying biology that may contribute to AD and other dementias.

The increasing evidence and understanding of SARS-CoV-2's impact on the CNS raises key questions on the impact for risk of later life cognitive decline, AD, and other dementia. This program of studies aims to better understand the long-term consequences that may impact the brain, cognition, and functioning-including the underlying biology that may contribute to AD and other dementias.Breastfeeding mothers often report perceived insufficient milk (PIM) believing their infant is crying too much, which leads to introducing formula and the early abandonment of breastfeeding. We sought to determine if infant crying was associated with reported PIM (yes/no) and number of problems associated with lactation (lactation problem score [LPS] 6-point Likert scale) before formula introduction. Primiparous breastfeeding mothers were recruited at birth and visited at 1, 2 and 4 weeks. Among those fully breastfeeding at 1 week (N = 230), infant crying variables based on maternal reports were not associated with PIM at 1 week, but LPS was. However, a mother's expectation that her infant would cry more than other infants was associated with increased odds of reporting PIM at 2 and 4 weeks, as were delayed onset of lactation and previous LPS. At 1 week, crying variables (frequency, difficulty in soothing) were associated with LPS along with percent weight change. Delayed onset of lactation, infant care style, number of breastfeeds and previous LPS were longitudinally associated with change in LPS from 1 to 2 weeks and 2 to 4 weeks. Our data suggest that reported infant crying is associated with PIM and LPS in the first 4 weeks of life. Guidance on what to expect in crying behaviour and the impact of infant care style may be beneficial in reducing PIM and LPS in the first month.The invasive pest whitefly (Bemisia tabaci) is a complex species, of which Middle East-Minor Asia 1 (MEAM1) and Mediterranean (MED) are the two most damaging members. Previous research showed that cabbage is frequently infested with MEAM1 but seldomly with MED, and this difference in performance is associated with glucosinolate (GS) content. Some insects can modify GS using glucosinolate sulfatase (SULF), the activity of which is regulated by sulfatase modifying factor 1 (SUMF1); therefore, to increase our understanding of different performances of MEAM1 and MED on cabbage plants, we identified and compared nine putative SULFs and one SUMF in MEAM1 and MED. We found that the lengths of two genes, BtSulf2 and BtSulf4, differed between MEAM1 and MED. The messenger RNA levels of BtSulf4 increased more than 20-fold after MEAM1 and MED adults were exposed to GS, but BtSulf2 expression was only induced by GS in MEAM1. Knockdown of BtSulf2 and BtSulf4 in MEAM1 resulted in a substantial increase in the mortality of GS-treated adults but not in MED. These results indicate that differences in BtSulf2 and BtSulf4 sequences and/or expression may explain why MEAM1 performs better than MED on cabbage. Our results provide a basis for future functional research on SULF and SUMF in B. tabaci.

The complexity of healthcare systems makes errors unavoidable. To strengthen the dialogue around how physicians experience and share medical errors, the objective of this study was to understand how generalist physicians make meaning of and grow from their medical errors.

This study used a narrative inquiry approach to conduct and analyse in-depth interviews from 26 physicians from the generalist specialties of emergency, internal, and family medicine. We gathered stories via individual interview, analysed them for key components, and rewrote a "meta-story" in a chronological sequence. We conceptualized the findings into a metaphor to draw similarities, learn from, and apply new principles from other fields of practice.

Through analysis we interpreted the story of a physician who is required to make numerous decisions in a short period of time in different clinical environments among the patient's family and whilst abiding by existing rules and regulations. Through sharing stories of success and failure, the clinical supervisor can help optimize the physician's emotional growth and professional development. Similarly, through sharing and learning from stories, colleagues and trainees can also contribute to the growth of the protagonist's character and the development of clinic, hospital, and healthcare system.

We draw parallels between the clinical setting and a generalist physician's experiences of a medical error with the environment and practices within professional sports. Using this comparison, we discuss the potential for meaningful coaching in medical education.

We draw parallels between the clinical setting and a generalist physician's experiences of a medical error with the environment and practices within professional sports. Using this comparison, we discuss the potential for meaningful coaching in medical education.Protein kinases are major players in various signal transduction pathways. Understanding the molecular mechanisms behind plant responses to biotic and abiotic stresses has become critical for developing and breeding climate-resilient crops. In this review, we summarize recent progress on understanding plant drought, salt, and cold stress responses, with a focus on signal perception and transduction by different protein kinases, especially sucrose nonfermenting1 (SNF1)-related protein kinases (SnRKs), mitogen-activated protein kinase (MAPK) cascades, calcium-dependent protein kinases (CDPKs/CPKs), and receptor-like kinases (RLKs). We also discuss future challenges in these research fields.

To review the techniques and available 2D and 3D computer-aided design (CAD) software programs to perform a diagnostic waxing for restorative procedures when cone beam computed tomography is not indicated.

An electronic review was performed in Medline, Embase, and Scopus search engines. A manual search was also conducted. The articles evaluating methods to obtain a 2D or 3D patient's representation for restorative dental procedures were included. A total of 33 articles were included for full text review. CAD programs provide the capability to integrate facial features from 2D photographs or 3D facial scans and facilitate facially driven digital diagnostic waxing procedures. Diagnostic and design tools varied among the programs, and multiple technique descriptions were found. However, the literature evaluating the accuracy of virtual patients and the perception variations between the 2D and 3D dimensional representations is limited.

The integration of digital technologies into treatment planning procedures introduce variation into the conventional interfaces; however, the concepts remain the same. Further studies are needed to evaluate the accuracy of the virtual representations and the influence of the type of dimensional representation on the esthetic perceptions among dental professionals.

The 2D and 3D CAD software programs facilitate the integration of facial features into digital diagnostic waxing procedures; however, the esthetic perception of the patient's virtual representation might vary among the different systems.

The 2D and 3D CAD software programs facilitate the integration of facial features into digital diagnostic waxing procedures; however, the esthetic perception of the patient's virtual representation might vary among the different systems.Immediate reutilization of discarded blood from surgery has not received much attention, leading to the waste of a large amount of autologous blood. We used a concentration gradient and high-voltage electrospinning technology to immediately prepare a scaffold material with high biological activity but without immunogenicity from autologous waste blood collected during surgery. Here, we fabricated and characterized a 90 mg/mL group, 110 mg/mL group, and 130 mg/mL group of fibrinogen (FBG) scaffolds. Analyses revealed that the FBG scaffolds had good film-forming properties and a clear fiber structure. in vitro cell viability experiments confirmed that the cells showed an increasing trend with increasing FBG concentrations. The cells grew well in the scaffold material and secreted more cell matrix. When human bone mesenchymal stem cells (hBMSCs) were cocultured with the scaffold material, the hBMSCs expressed osteogenic and chondrogenic biomarkers. The cellular scaffold complexes from the 3 groups were implanted in four full-thickness round wounds (Φ12 mm) on the dorsal back of each rat, the 130 mg/mL group showed a 90% reduction in wound size and the data compared to other groups were better at 14 day. These results suggest that electrospinning technology-based FBG scaffold materials derived from autologous waste blood may become an ideal tissue engineering scaffold and can be immediately used for autologous hemostasis, anti-adhesion films, and wound dressing in surgery.This work aimed at studying the unconfirmed hypothesis predicting the existence of a connection between coffee farm microbiome and the resulting spontaneous fermentation process. Using Illumina-based amplicon sequencing, 360 prokaryotes and 397 eukaryotes were identified from coffee fruits and leaves, over-ripe fruits, water used for coffee de-pulping, depulped coffee beans, soil, and temporal fermentation samples at an experimental farm in Honduras. Coffee fruits and leaves were mainly associated with high incidence of Enterobacteriaceae, Pseudomonas, Colletotrichum, and Cladosporium. The proportion of Enterobacteriaceae was increased when leaves and fruits were collected on the ground compared to those from the coffee tree. Coffee farm soil showed the richest microbial diversity with marked presence of Bacillus. Following the fermentation process, microorganisms present in depulped coffee beans (Leuconostoc, Gluconobater, Pichia, Hanseniaspora, and Candida) represented more than 90% of the total microbial community, which produced lactic acid, ethanol, and several volatile compounds. The community ecology connections described in this study showed that coffee fruit provides beneficial microorganisms for the fermentation process. Enterobacteria, Colletotrichum, and other microbial groups present in leaves, fruit surface, over-ripe fruits, and soil may transfer unwanted aromas to coffee beans, so they should be avoided from having access to the fermentation tank.Retinoblastoma protein (RB) encoded by Rb1 is a prominent inducer of cell cycle arrest (CCA). The hormone progesterone (P4 ) promotes CCA in the uterine epithelium and previous studies indicated that P4 activates RB by reducing the phosphorylated, inactive form of RB. Here, we show that embryo implantation is impaired in uterine-specific Rb1 knockout mice. We observe persistent cell proliferation of the Rb1-deficient uterine epithelium until embryo attachment, loss of epithelial necroptosis, and trophoblast phagocytosis, which correlates with subsequent embryo invasion failure, indicating that Rb1-induced CCA and necroptosis of uterine epithelium are involved in embryo invasion. Pre-implantation P4 supplementation is sufficient to restore these defects and embryo invasion. In Rb1-deficient uterine epithelial cells, TNFα-primed necroptosis is impaired, which is rescued by the treatment with a CCA inducer thymidine or P4 through the upregulation of TNF receptor type 2. TNFα is expressed in the luminal epithelium and the embryo at the embryo attachment site. These results provide evidence that uterine Rb1-induced CCA is involved in TNFα-primed epithelial necroptosis at the implantation site for successful embryo invasion.Highlights A clinical pharmacist using recommendations of Food and Drug Administration-cleared computerized insulin dose adjustment algorithms based on analyses of glucose readings from continuous glucose monitoring (Abbot Free Style Pro) in 13 poorly controlled insulin-requiring diabetic patients increased time in target range of 3.9 to 10.0 mmol/L from 29% to 51% and decreased time in range of >13.9 mmol/L from 43% to 23% (both P = 0.01) after 3 months. Glycated hemoglobin (HbA1c) levels (±SD) fell from 102 (±15) to 67 (±10) mmol/mol (P less then  10-6 ).

Sublingual immunotherapy (SLIT) has been deployed in humans and dogs; to the best of the authors' knowledge, there are no published studies about the use of SLIT in cats.

Evaluate the clinical efficacy of SLIT in atopic cats sensitized to dust and storage mites, assessing immunological changes associated with SLIT treatment.

Twenty-two client-owned cats with clinical signs compatible with feline atopic dermatitis (fAD) and serum allergen-specific immunoglobulin (Ig)E against house dust and storage mites.

Prospective, multicentre, open-label clinical trial. Individualized mite-specific SLIT was administered orally for 12months. All cats underwent clinical examination to record SCORing feline allergic dermatitis (SCORFAD), pruritus Visual Analog Scale (pVAS) and serum allergen-specific IgE and IgG, every three months for 12months.

Sixteen of 22 cats (73%) completed the study and three of six cats withdrawn from the study were included in an intention-to-treat analysis. SCORFAD and pVAS values decreased significantly from baseline (T0) to the third month of treatment (P=0.0004 and P=0.0013, respectively), with median total values ranging from 19 (6-44) (T0) to 2.5 (0-17) (T12) (P=0.0001), and from 8 (6-10) (T0) to 2.3 (0-8) (T12) (P=0.0001), respectively. Allergen-specific IgE values decreased significantly from the ninth month (T9) of treatment (P=0.0032), with median scores decreasing from 56 (12-729) (T0) to 34 (0-158) (T12) (P=0.0208). No significant differences in allergen-specific IgG values were observed throughout the study. No adverse effects related to the use of SLIT were reported.

Sublingual immunotherapy should be considered a rapid, effective, safe and well-tolerated treatment in cats with feline atopic dermatitis fAD.

Sublingual immunotherapy should be considered a rapid, effective, safe and well-tolerated treatment in cats with feline atopic dermatitis fAD.

Canine otitis externa (OE) is a common disease characterised by inflammation of the epithelial tissue of the external ear canal. Secondary infections are frequent, and Malassezia pachydermatis and Staphylococcus pseudintermedius are routinely isolated and treated with antifungal and antibiotic compounds.

To analyse the otitis ear microbiome before and after a treatment with prednisolone plus pomegranate or antimicrobial drugs ANIMALS 15 dogs with nonpurulent OE.

A 30 day, double-blinded, multicentre, randomized and controlled parallel-group (11) trial was conducted in 15 dogs with nonpurulent OE, following two different topical treatments (prednisolone plus pomegranate versus prednisolone plus antibiotic and antifungal drugs). On days (D)0, D15 and D30, serum and skin otic samples were collected, and clinical examination and microbiome analysis (bacteria and fungi) were performed. Results were compared with validated otitis clinical scores to assess the effectiveness of both treatments.

Nine bacterial and four fungal families were detected during the three time-points tested. An increase in fungal diversity (Shannon index) and composition was the most significant change observed after both treatments. At treatment D15 and D30, the reduction in clinical signs was statistically significant in both treatment groups (P≤0.05). Prednisolone plus pomegranate cleanser treatment was able to control the clinical signs of otitis as well as the bacterial and fungal overgrowth.

Mild otitis cases associated with microbial overgrowth may be managed with topical antiseptic and anti-inflammatory agents without the need for antibiotic and/or antifungal compounds.

Mild otitis cases associated with microbial overgrowth may be managed with topical antiseptic and anti-inflammatory agents without the need for antibiotic and/or antifungal compounds.Fifty-six piglets were weaned at 21 days and randomly assigned to 1 of 8 dietary treatments with 7 replicate pens for a 14-day experimental period. The eight experimental diets were prepared via a 2 × 4 factorial arrangement with citric acid (CA; 0 and 0.3%) and dietary electrolyte balance (dEB, Na +K - Cl mEq/kg of the diet; -50, 100, 250, and 400 mEq/kg). Varying dEB values were obtained by altering calcium chloride and sodium bicarbonate contents. Dietary CA significantly increased (p less then .05) villus height (VH) and villus heightcrypt depth (VHCD) in the jejunum. Piglets fed a 250 mEq/kg diet increased (p less then .05) VH and VHCD values in the duodenum. Jejunal VH and VHCD increased (quadratic; p less then .05), and ileal VHCD (liner and quadratic; p less then .05) decreased as dEB was increased in diets without CA, but no such effect was observed on the diets containing CA (dEB ×CA; p less then .05). The CD in jejunum (quadratic; p less then .05) increased as dEB was increased in diets containing CA, whereas it was decreased (linear; p less then .05) in the diets without CA (dEB ×CA; p less then .001). Dietary CA increased maltase activity and reduced the number of Ki67-positive cells (p less then .05). Increasing dEB values in diets without CA increased sucrose and lactase activities (quadratic; p less then .05), but no such effect was observed in the diets with CA (dEB ×CA; p less then .05). An interaction effect between dEB and CA on the number of Ki67-positive cells was observed (p less then .001). In conclusion, 250 mEq/kg dEB diet with CA improved piglet intestinal digestion and absorption function by improving intestinal morphology and increasing digestive enzyme activities. However, these improvements were also observed in piglets fed the 100 mEq/kg dEB diet without CA.Skin covers the entire body and is the largest organ. Skin cancer is one of the most dreadful cancers that is primarily triggered by sensitivity to ultraviolet rays from the sun. However, the riskiest is melanoma, although it starts in a few different ways. The patient is extremely unaware of recognizing skin malignant growth at the initial stage. Literature is evident that various handcrafted and automatic deep learning features are employed to diagnose skin cancer using the traditional machine and deep learning techniques. The current research presents a comparison of skin cancer diagnosis techniques using handcrafted and non-handcrafted features. Additionally, clinical features such as Menzies method, seven-point detection, asymmetry, border color and diameter, visual textures (GRC), local binary patterns, Gabor filters, random fields of Markov, fractal dimension, and an oriental histography are also explored in the process of skin cancer detection. Several parameters, such as jacquard index, accuracy, dice efficiency, preciseness, sensitivity, and specificity, are compared on benchmark data sets to assess reported techniques. Finally, publicly available skin cancer data sets are described and the remaining issues are highlighted.Availability of the essential macronutrient nitrogen in soil plays a critical role in plant growth, development, and impacts agricultural productivity. Plants have evolved different strategies for sensing and responding to heterogeneous nitrogen distribution. Modulation of root system architecture, including primary root growth and branching, is among the most essential plant adaptions to ensure adequate nitrogen acquisition. However, the immediate molecular pathways coordinating the adjustment of root growth in response to distinct nitrogen sources, such as nitrate or ammonium, are poorly understood. Here, we show that growth as manifested by cell division and elongation is synchronized by coordinated auxin flux between two adjacent outer tissue layers of the root. This coordination is achieved by nitrate-dependent dephosphorylation of the PIN2 auxin efflux carrier at a previously uncharacterized phosphorylation site, leading to subsequent PIN2 lateralization and thereby regulating auxin flow between adjacent tissues. A dynamic computer model based on our experimental data successfully recapitulates experimental observations. Our study provides mechanistic insights broadening our understanding of root growth mechanisms in dynamic environments.

To describe the presentation, diagnosis, treatment, and outcome for horses with fibro-osseous lesions of the craniofacial complex.

Retrospective multicenter case series.

Thirty horses evaluated for fibro-osseous lesions of the skull from January 1, 2001 through December 31, 2019 in four centers.

Medical records were reviewed for signalment, clinical presentation, histological and diagnostic imaging findings, treatment instituted, and outcome. Long-term outcome information was obtained by owner questionnaire or the medical record.

Diagnoses included ossifying fibroma in 20 of 30 horses, osteoma in eight of 30 horses, and fibrous dysplasia in two of 30 horses. Twelve of 30 lesions were diagnosed in horses <1 year old, and 20 of 30 lesions originated from the rostral mandible. The most common treatment was rostral mandibulectomy. Recurrence was not reported after complete excision. Incomplete excision was confirmed in eight horses (four ossifying fibromas, three osteomas, and one fibrous dysplasia), even when complete surgical margins are not obtained.The α-isozyme of diacylglycerol kinase (DGK) enhances cancer cell proliferation and, conversely, it promotes the nonresponsive immune state known as T-cell anergy. Moreover, a DGKα-selective inhibitor, CU-3, induced cell death in cancer-derived cells and simultaneously enhanced T-cell interleukin-2 production. In addition to DGKα, DGKζ is also known to induce T-cell anergy. In the present study, we examined whether combined inhibition/silencing of DGKα and DGKζ synergistically enhanced T-cell activity. Combined treatment with CU-3 or DGKα-small interfering RNA (siRNA) and DGKζ-siRNA more potently enhanced T-cell receptor-crosslink-dependent interleukin-2 production in Jurkat T cells than treatment with either alone. Intriguingly, in addition to activating T cells, dual inhibition/silencing of DGKα and DGKζ synergistically reduced viability and increased caspase 3/7 activity in AKI melanoma cells. Taken together, these results indicate that combined inhibition/silencing of DGKα and DGKζ simultaneously and synergistically enhances interleukin-2 production in T cells and induces cell death in melanoma. Therefore, dual inhibition/silencing of these DGK isozymes represents an ideal therapy that potently attenuates cancer cell proliferation and simultaneously enhances immune responses that impact anticancer immunity.The external morphology, internal oral morphology, the chondrocranium and the hyobranchial apparatus of Elachistocleis bumbameuboi, E. cf. piauiensis, E. cesarii and E. bicolor are described and compared with each other and with other species of microhylids using available descriptions from the literature. The general morphology of Elachistocleis species is conservative in many aspects. Differences between species are subtle and are found in the body shape, the edge of the snout, fin height, if the lateral line is evident, the presence of regular pustules in the buccal roof arena, the posterolateral edge of the cartilago suprarostralis, the shape of the fenestra in the occipital region, presence or absence of fenestra hypophysea, the margin of the processus antorbitalis, expansions in the ventrolateral process, the shape and inclination of the fenestra subocularis, whether the subotic process is single or slightly bifid, and the inclination of the processus anterolateralis hyalis.

To assess the ability of ultra-short echo time (UTE)-MRI to detect subglottic stenosis (SGS) and evaluate response to balloon dilation. To correlate measurements from UTE-MRI with endotracheal-tube (ETT)-sizing and to investigate whether SGS causes change in airway dynamics.

Animal research study.

Eight adult New-Zealand white rabbits were used as they approximate neonatal airway-size. The airways were measured using ETT-sizing and 3D UTE-MRI at baseline, 2 weeks post-cauterization induced SGS injury, and post-balloon dilation treatment. UTE-MR images were acquired to determine airway anatomy and motion. Airways were segmented from MR images. Cross-sectional area (CSA), major and minor diameters (D

and D

), and eccentricity were measured.

Post-injury CSA at SGS was significantly reduced (mean 38%) compared to baseline (P = .003) using UTE-MRI. ETT-sizing correlated significantly with MRI-measured CSA at the SGS location (r = 0.6; P < .01), particularly at the post-injury timepoint (r = 0.93; P < .01). Outer diameter from ETT-sizing (OD) correlated significantly with D

(r = 0.63; P < .01) from UTE-MRI at the SGS location, especially for the post-injury timepoint (r = 0.91; P < .01). Mean CSA of upper trachea did not change significantly between end-expiration and end-inspiration at any timepoint (all P > .05). Eccentricity of the upper trachea increased significantly post-balloon dilation (P < .05).

UTE-MRI successfully detected SGS and treatment response in the rabbit model, with good correlation to ETT-sizing. Balloon dilation increased CSA at SGS, but not to baseline values. SGS did not alter dynamic motion for the trachea in this rabbit model; however, tracheas were significantly eccentric post-balloon dilation. UTE-MRI can detect SGS without sedation or ionizing radiation and may be a non-invasive alternative to ETT-sizing.

NA Laryngoscope, 131E1971-E1979, 2021.

NA Laryngoscope, 131E1971-E1979, 2021.Research has shown that identity in adolescence takes the shape of a coherent life story that integrates the past with the present self and provides meaning and purpose in the person's life. One stable feature of narrative identity identified in adults is emotional tone. Here, the development of emotional tone in life stories was investigated across childhood and adolescence. A total of 142 adolescents aged 10 to 14 years wrote about their past weekend, their past and future life stories and generated a cultural life script. Across age groups, adolescents told past life stories that were overall mixed (both positive and negative) or moderately positive in emotional tone, and future life stories that were positive or highly positive. In relation to life story development, we replicated findings on age-related development of life story coherence in both past and future life stories in 10-14-year-olds. Lastly, the study highlights the link between life story coherence and cultural life script abilities. Cultural life script typicality was linked to life story coherence for both past and future life stories and across all age groups, and a majority of events mentioned in future life stories overlapped with cultural life script events.

To develop an age-dependent model to estimate the positions of the ocular and lenticular principal planes (pps) for use in ocular and axial power calculations.

Ocular power of the eye (P

) and axial power (P

) were calculated based on previously published average data of the ocular biometry and refraction in newborn infants, children and adults, as well as the associated pp positions. Next, regressions of the pp positions were made as a function of the logarithm of age, which were subsequently used to estimate P

and P

. These regression-based estimates were compared with the original data for validation. Finally, this procedure was repeated using the Atchison myopic eye model to determine the influence of myopia on the regression estimates.

In adults, the corneal pps almost coincide at 0.058mm in front of the cornea. The first lenticular pp position relative to the corneal apex is described by the equation 5.809 - 0.697·exp(-0.211·Age) (r

=0.96), and the second lenticular pp by 6.026 - 0.684·et to the corneal apex.

We investigated growth patterns and pathological features in intermediate-size laryngeal carcinoma amenable to supraglottic laryngectomy.

Retrospective cohort study.

We reviewed patients who underwent an open partial horizontal laryngectomy (OPHL) type I. We analyzed pathological data, tumor sizes, overall survival, disease-specific survival, local control, and laryngeal preservation. Results were stratified between three groups group I comprised patients with endolaryngeal carcinoma, group II comprised patients with anterior epilaryngeal carcinoma who underwent an OPHL type I + base of tongue (BOT), group III comprised patients with lateral epilaryngeal carcinoma who underwent an OPHL type I + pyriform sinus (PIR).

Sixty-eight patients were analyzed. The 5-year rates of overall survival, disease-specific survival, local control, and laryngeal preservation were 68.4%, 83.7%, 91.6%, and 98.3%, respectively. The tumor sizes at pathological examination were similar between the three groups (mean 27 mm, P = .80) and were associated with pathological features, notably pre-epiglottic space (PES) invasion (24.9 mm vs. 32.2 mm, P = .01), occult invaded lymph nodes (22.6 mm vs. 29.9 mm, P = .03), and trends for margins status (26.5 mm vs. 29.3 mm, P = .45). The risks of PES invasion, occult lymph nodes, and positive margins, respectively, predominated in group I (41.7%), group II (56.3%), and group III (23.3%).

In intermediate-size tumors amenable to supraglottic laryngectomy, pathological features are associated with tumor size according to group stratification based on tumor location.

4 Laryngoscope, 131E1980-E1986, 2021.

4 Laryngoscope, 131E1980-E1986, 2021.

Precise placement of stimulating and recording electrodes is vital when performing nerve conduction studies (NCSs). In this study, we aimed to determine whether ultrasonography (US) was more precise in localizing the superficial radial nerve (SRN), dorsal ulnar cutaneous nerve (DUCN), ulnar nerve (UN) crossing the cubital tunnel, and radial nerve (RN) crossing the spiral groove (SG) compared to conventional techniques.

Thirty healthy young subjects (15 male) were recruited. Each subject underwent both landmark-based and US-guided NCS. Onset latencies and amplitudes of compound motor action potentials (CMAPs) and sensory nerve action potentials (SNAPs), and stimulation levels (ie, intensity × duration) required to obtain maximal CMAP amplitudes were compared between the two techniques.

The mean CMAP amplitudes of the UN above the cubital tunnel (9.55 ± 1.96 vs 8.96 ± 1.94 mV, P = .030), UN below the cubital tunnel (10.11 ± 2.07 vs 9.37 ± 1.95 mV, P < .001), and RN below the SG (5.21 ± 1.56 vs 4.34 ± 1.03 mV, P < .001) were significantly greater using US-guided NCSs compared to landmark-based NCSs. The mean onset latency of the DUCN was significantly shorter using US-guided NCSs (1.49 ± 0.15 vs 1.57 ± 0.14 ms, P = .020). The required stimulation level in the UN and RN was significantly lower using US-guided NCSs.

When performing NCSs, US guidance provides a more precise localization of the stimulator and electrodes for the DUCN, UN, and RN, while providing comparable localization for the SRN, compared to landmark-based techniques.

When performing NCSs, US guidance provides a more precise localization of the stimulator and electrodes for the DUCN, UN, and RN, while providing comparable localization for the SRN, compared to landmark-based techniques.

Identify placental pathology-related complications, labor and neonatal outcomes in pregnancies complicated by pathological nuchal translucency (NT) with normal microarray analysis.

A retrospective study in which all women with singleton pregnancy who demonstrated NT above 3mm and a normal microarray analysis were matched to women with normal NT and a normal microarray analysis (2013-2019) in a single tertiary academic center. The following placental pathology-related parameters were measured preeclampsia, oligohydramnios, suspected intrauterine growth restriction, abnormal Doppler studies or small for gestational age (SGA) neonates. The primary outcome was defined as a composite of complications related to placental pathology including preeclampsia and SGA neonate. Secondary outcomes were labor complications and neonatal morbidity.

A total of 185 women were included in the study of them, 47 presented an abnormal NT (study group) and 138 presented normal NT (controls). Groups did not significantly differ in baseline characteristics. Regarding primary outcome, all placental-related complications frequencies were higher in the study group, with a composite rate of 17.02% versus 6.52% in controls (p=0.042%). Secondary outcomes did not differ between groups.

Abnormal NT measurement presented in pregnancies with normal fetal microarray analysis is associated with higher rates of placental-related complications.

Abnormal NT measurement presented in pregnancies with normal fetal microarray analysis is associated with higher rates of placental-related complications.RYamides constitute a novel family of neuropeptides newly identified in insects, and play important roles in regulating a variety of physiological processes. However, the signaling characteristics and physiological actions of RYamide signaling system remain largely unknown. In the present study, we cloned the full-length complementary DNA of the RYamide receptor BNGR-A19 from Bombyx mori larvae. After expression in mammalian HEK293T and insect Sf9 cells, functional assays revealed that BNGR-A19 was activated by synthetic RYamide peptides, triggering a significant increase in cAMP-response element controlled luciferase activity and Ca2+ mobilization in a Gq inhibitor-sensitive manner. Upon activation by RYamide peptides, BNGR-A19 elicited ERK1/2 phosphorylation via a Gq -PLC-PKC pathway, and also underwent a rapid internalization from the cell surface to the cytoplasm. Further cross-activity analysis indicated that BNGR-A19 exhibited very weak response upon stimulation by high concentration (1 μM) of Bombyx sulfakinin-1, neuropeptide F-1, and short neuropeptide F-1, and vice versa, Bombyx RYamides also showed slight potency for activating Bombyx NPF receptor (BNGR-A4) and sNPF receptor (BNGR-A11). In addition, the quantitative reverse-transcription polymerase chain reaction results showed that the high-level expression of BNGR-A19 was detected in the hindgut and testis, suggesting that the RYamide signaling is likely involved in the regulation of feeding, water homeostasis and testis development. This study provides the first in-depth information on the insect RYamide signaling system, facilitating the further clarification of its endocrinological roles in insect physiology.HnRNPA2/B1 is highly expressed in many tumors. However, the role of hnRNPA2/B1 in breast cancer is not clear. In this study, we found the proliferation rate was decreased after knockout of hnRNPA2/B1 by CRISPR-CAS9 in MCF-7 cells, as demonstrated by the reduced expression of CDK4 and p-AKT, and the increased expression of P27. Besides this, the western blot results showed that knockout of hnRNPA2/B1 increased the rate of apoptosis and declined autophagy. By in vivo assay, we found that knockout of hnRNPA2/B1 suppressed tumor growth in a xenograft mouse model. Immunohistochemical staining results confirmed knockout of hnRNPA2/B1 impaired tumor angiogenesis, as illustrated by downregulated expression of VEGF-A. Besides this, interacting proteins with hnRNPA2/B1 were identified by mass spectrometry and the PPI network was constructed. GO analysis suggests that the Interacting proteins are mainly enriched in the Wnt signaling pathway, tumor necrosis factor-mediated signaling pathway, translation, and so on. We then identified hnRNPA2/B1 interacted with signal transducer and activator of transcription 3 (STAT3), as supported by the colocalization of hnRNPA2/B1 and STAT3. Meanwhile, knockout of hnRNPA2/B1 inhibited the phosphorylation of STAT3. Collectively, our results demonstrate that hnRNPA2/B1 promotes tumor cell growth in vitro and in vivo by activating the STAT3 pathway, regulating apoptosis and autophagy.Attachment theory proposes that children's representations of interactions with caregivers guide information-processing about others, bridging interpersonal domains. In a longitudinal study (N = 165), preschoolers (Mage = 5.19 years) completed the MacArthur Story Stem Battery to assess parent representations. At school-age (Mage = 8.42 years), children played a virtual ballgame with peers who eventually excluded them to track event-related cardiac slowing, a physiological correlate of rejection, especially when unexpected. At both ages, parents and teachers reported on peer and emotional problems. During exclusion versus inclusion-related events, cardiac slowing was associated with greater positive parent representations and fewer emerging peer problems. Cardiac slowing served as a mediator between positive parent representations and peer problems, supporting a potential psychophysiological mechanism underlying the generalization of attachment-related representations to peer relationships.

To characterize patterns of weight-related self-monitoring (WRSM) among US undergraduate and graduate students and examine associations between identified patterns of WRSM and eating disorder symptomology.

Undergraduate and graduate students from 12 US colleges and universities (N = 10,010) reported the frequency with which they use WRSM, including self-weighing and dietary self-monitoring. Eating disorder symptomology was assessed using the Eating Disorder Examination Questionnaire. Gender-specific patterns of WRSM were identified using latent class analysis, and logistic regressions were used to identify differences in the odds of eating disorder symptomology across patterns of WRSM.

Among this sample, 32.7% weighed themselves regularly; 44.1% reported knowing the nutrition facts of the foods they ate; 33.6% reported knowing the caloric content of the foods they ate; and 12.8% counted the calories they ate. Among women, four patterns of WRSM were identified "no WRSM," "all forms of WRSM," "knowing nutr symptomology.The development of immune checkpoint inhibitor (ICI) therapy with anti-CTLA-4 and anti-PD-1/L1 monoclonal antibodies has led to a paradigm shift in cancer therapy. ICI neoadjuvant therapy followed by surgery has become the standard of care for several advanced-stage cancers. The pathology associated with ICI therapy is vast and includes neoadjuvant-associated tissue reactions and activation of tertiary lymphoid structures (TLSs) at the site of the tumor bed and off-target immune-related adverse events. TLSs are thought to recapitulate lymph node function and may act as localized immune machinery to mount an antitumor response. B-cell activation in TLSs during neoadjuvant ICI therapy has been correlated with antitumor response. We report a patient with a history of sarcomatoid squamous cell carcinoma treated with neoadjuvant ICI cemiplimab who developed clonal expansion of B-cells in the TLSs of the tumor bed. The TLSs morphologically mimicked a cutaneous marginal zone lymphoma with plasmacytic differentiation. Awareness of clonal expansion of B-cells in TLSs during neoadjuvant ICI therapy is critical to recognize a response to ICI therapy and to avoiding an incorrect diagnosis of low-grade B-cell lymphoma.As a posttranscriptional regulatory factor, microRNA (miRNA) plays an important role in the formation of myotubes. However, little is known about the mechanism of miRNA regulating myotube morphogenesis. Here, we aimed to characterize the function of miR-455-5p in myotube morphogenesis by inducing differentiation in C2C12 myoblasts containing murine Mylip fragments with the miR-455-5p target sequence. We found that miR-455-5p overexpression promoted the differentiation and hypertrophy of myotubes, while miR-455-5p inhibition led to the failure of myotube differentiation and formation of short myotubes. Furthermore, we demonstrated that miR-455-5p directly targeted the Mylip 3'-untranslated region, which plays a key role in monitoring myotube morphogenesis. Interestingly, the expression and function of Mylip were opposite to those of miR-455-5p during myogenesis. Our data uncovered novel miR-455-5p targets and established a functional link between Mylip and myotube morphogenesis. Understanding the involvement of Mylip in myotube morphogenesis provides insight into the function of the gene regulatory network.In this work, the kinetic model based on the previously developed metabolic and glycan reaction networks of the ovarian cells of the Chinese hamster ovary (CHO) cell line was improved by the inclusion of transcriptomic data that took into account the values of the RPKM gene (Reads per Kilobase of Exon per Million Reads Mapped). The transcriptomic (RNASeq) data were obtained together with metabolic and glycan data from the literature, and the concentrations with RPKM values were collected at several points in time from two fed-batch processes. First, the fluxes were determined by regression analysis of the metabolic data, then these fluxes were corrected by using the fold change in gene expression as a measure of enzyme concentrations. Next, the corrected fluxes in the kinetic model were used to calculate the concentration profiles of the metabolites, and literature data were used to evaluate the predicted results of the model. Compared to other studies where the concentration profiles of CHO cell metabolites were described using a kinetic model without consideration of RNA-Seq data to correct the fluxes, this model is unique. The additional integration of transcriptomic data led to better predictions of metabolic concentrations in the fed-batch process, which is a significant improvement of the modelling technique used.Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life-threatening hyperthermic reaction occurring during general anaesthesia. Malignant hyperthermia has an underlying genetic basis, and genetically susceptible individuals are at risk of developing malignant hyperthermia if they are exposed to any of the potent inhalational anaesthetics or suxamethonium. It can also be described as a malignant hypermetabolic syndrome. There are no specific clinical features of malignant hyperthermia and the condition may prove fatal unless it is recognised in its early stages and treatment is promptly and aggressively implemented. The Association of Anaesthetists has previously produced crisis management guidelines intended to be displayed in all anaesthetic rooms as an aide memoire should a malignant hyperthermia reaction occur. The last iteration was produced in 2011 and since then there have been some developments requiring an update. In these guidelines we will provide background information that has been used in updating the crisis management recommendations but will also provide more detailed guidance on the clinical diagnosis of malignant hyperthermia. The scope of these guidelines is extended to include practical guidance for anaesthetists dealing with a case of suspected malignant hyperthermia once the acute reaction has been reversed. This includes information on care and monitoring during and after the event; appropriate equipment and resuscitative measures within the operating theatre and ICU; the importance of communication and teamwork; guidance on counselling of the patient and their family; and how to make a referral of the patient for confirmation of the diagnosis. We also review which patients presenting for surgery may be at increased risk of developing malignant hyperthermia under anaesthesia and what precautions should be taken during the peri-operative management of the patients.