• Rodriquez Madden opublikował 5 miesięcy, 1 tydzień temu

    After hospital mergers, unit work environments are at risk of being unhealthy due to poor intradisciplinary two-way communication in times of change. This quality improvement project explored the impact a 4-week, social-media-based, intradisciplinary communication strategy had on a postmerger intensive care unit work environment. The sample (N = 14) included 11 bedside nurses and three administrative nurses working in a 22-bed southwestern US ICU. The participants took part in a Facebook closed-group community of practice called Nurse to Nurse, with a total of 25.9% participation rate. Eleven participants completed the pre-Nurse to Nurse survey, a 20.4% completion rate, while eight participants completed the post-Nurse to Nurse survey, a 14.8% completion rate. After the conclusion of Nurse to Nurse, the overall mean skilled communication survey score increased to 3.79, a 1.6% improvement. Question 14, which measured zero-tolerance behavior perception, exhibited a mean of 2.3% improvement, boosting this metric to excellent status. Utilization data revealed 68 comments posted within Nurse to Nurse implementation, with 56 showing horizontal communication (73.5%) and 24 displaying vertical communication (26.5%). A total of 217 bedside nurse views (81.3%) and 50 administrative nurse views (18.7%) were noted. Nurse to Nurse, an online communication-focused community of practice, enhanced communication among bedside and administrative nurses working in a postmerger intensive care unit setting.The development of driveline infections following left ventricular assist device (LVAD) implantation remains a major problem. We investigated the impact of fluorescence in situ hybridization (FISH) combined with 16S rRNA gene sequencing on the diagnosis of driveline infections. LVAD drivelines (n = 61) from 60 consecutive patients were obtained during LVAD explantation and subjected to FISH analysis. 16S rRNA gene polymerase chain reaction (PCR) and sequencing to identify the microorganisms were performed. Results were compared with those of a standard microbiological culture. The reasons for pump removal were heart transplantation (n = 22), weaning (n = 14), pump exchange due to pump thrombosis (n = 12), technical problems (n = 7), or death (n = 5). Of the 60 patients, 26 exhibited clinical signs of a VAD-specific infection, while 34 (with 35 drivelines) showed no clinical signs of infection before explantation. The spectrum of identified pathogens differed between FISH/PCR and conventional microbiological diagnostics. In general, the bacterial spectrum was more diverse in FISH/PCR as compared with conventional microbiology, which more often showed only typical skin flora (coagulase-negative staphylococci and Corynebacteriaceae). In addition to identifying the species, FISH/PCR provided information about the spatial distribution and invasiveness of the microorganisms. Cultures usually represent the only source of microbiological information for clinicians and often prove to be unsatisfactory in complex LVAD cases. FISH/PCR not only identified a greater number and variety of microorganisms than standard culture did, but it also provided information about the number, localization, and biofilm state of the pathogens, making it a useful tool for diagnosing the specific cause of LVAD driveline infections.

    To investigate the cross-section shape of the femoral neck isthmus (FNI) in three-dimensional reconstruction model of the femoral neck.

    From December 2009 to December 2012, computed tomography (CT) data of bilateral hip joint from 200 consecutive patients (137 males and 63 females, 69.41 ± 9.21 years old, ranged from 50-85 years old) who underwent surgical treatments for proximal femoral fracture were retrospectively reviewed. The 3D model of the proximal femur was reconstructed, and the „inertia axis” method, which was applied to measure the long and short axes of the cross-section of the FNI, was established. The cross-sectional area and perimeter were calculated by a formula using the length of the long and short axes and then compared with the actual measured values by the software. Correlation between the descriptive parameters of the FNI cross-section (area, perimeter, and eccentricity) and patients’ demographics (age, height, and weight) was analyzed. Stepwise linear regression analysis was used toaccording to the inertia axis, and the findings proposed an anatomical basis for the further study of the spatial configuration of cannulated screws in the treatment of femoral neck fractures.

    The cross-section shape of the FNI appears to be oval-like in the 3D model, which is separated according to the inertia axis, and the findings proposed an anatomical basis for the further study of the spatial configuration of cannulated screws in the treatment of femoral neck fractures.

    To explore the clinical features, surgical interventions and prognosis of injured eyes following explosion and to develop the risk factors for poor prognosis.

    A nested case-control study. To the date of 31 December 2018, 99 explosion-related eye globes were selected from the Eye Injury Vitrectomy Study database, which is a multicenter prospective cohort study and began in 1990s. All cases selected underwent vitreoretinal surgery or enucleation and were followed up for at least 6months. Clinically meaningful preoperative variables and outcomes were used to develop logistic regression models.

    The unfavourable outcomes were defined as silicone oil-filled eyes, phthisis bulbi, enucleation and anatomically restored eyes whose final BCVA is worse than initial vision after 6months of follow-up. The proportion of unfavourable outcomes was 92.0%, 60.9% and 66.7% in large festive fireworks, detonator and beer bottle groups respective. The anatomic and visual outcome of injured eyes with combined injury of blast wauma. The mechanism of open globe mixture and close globe mixture in explosion-related eye trauma need more cases and participating units to explore together in the future.White matter hyperintensities (WMH) are common in elderly individuals and cause brain network deficits. However, it is still unclear how the global brain network is affected by the focal WMH. We aimed to investigate the diffusion of WMH-related deficits along the connecting white matters (WM). Brain magnetic resonance imaging data and neuropsychological evaluations of 174 participants (aged 74 ± 5 years) were collected and analyzed. For each participant, WMH lesions were segmented using a deep learning method, and 18 major WM tracts were reconstructed using automated quantitative tractography. The diffusion characteristics of distal WM tracts (with the WMH penumbra excluded) were calculated. Multivariable linear regression analysis was performed. We found that a high burden of tract-specific WMH was related to worse diffusion characteristics of distal WM tracts in a wide range of WM tracts, including the forceps major (FMA), forceps minor (FMI), anterior thalamic radiation (ATR), cingulum cingulate gyrus (CCG), corticospinal tract (CST), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus-parietal (SLFP), superior longitudinal fasciculus-temporal (SLFT), and uncinate fasciculus (UNC). Furthermore, a higher mean diffusivity (MD) of distal tracts was linked to worse attention and executive function in the FMI, right CCG, left ILF, SLFP, SLFT, and UNC. The effect of WMH on the microstructural integrity of WM tracts may propagate along tracts to distal regions beyond the penumbra and might eventually affect attention and executive function.Orderly and stage-specifically expressed proteins are essential for spermatogenesis, and proteases play a key role in protein activation and function. The present study aimed to investigate serine protease 55 (PRSS55), which was reported to play a role in sperm-uterotubal junction (UTJ) migration and sperm-zona pellucida (ZP) binding. We found that PRSS55 was specifically expressed in testicular spermatids and epididymal spermatozoa. By constructing knockout mice targeting all transcripts of Prss55, we demonstrated that deletion of Prss55 resulted in a serious decline of male fertility, with significantly increased sperm malformation and decreased sperm motility. In Prss55-/- mice, increased structural abnormality, including deficient „9 + 2” microtubules, damaged peripheral dense fibre, and defective mitochondrial cristae, were found in sperm. In addition, sperm showed decreased expression of electron transfer chain molecules and lower ATP contents. These could be the potential causes of the astheno/teratozoospermia phenotype of the Prss55-/- mice, and provided new evidence for the previously reported impaired sperm-UTJ migration. Moreover, preliminary studies allowed us to speculate that PRSS55 might function by activating type II muscle myosin in the testis, which is involved in many processes requiring motivation and cytoskeleton translocation. Thus, PRSS55 is essential for the structural differentiation and energy metabolism of sperm, and might be a potential pathogenic factor in astheno/teratozoospermia. Our results provide an additional explanation for the male sterility of Prss55-/- mice, and further reveal the role of PRSS55.To create high-quality eggs by using different breed and feed materials, we investigated free amino acid contents and taste sensor traits using two chicken breeds (Rhode Island Red; RIR and Australorp; AUS) fed two feeds (mixed and fermented feeds). Two-way ANOVA revealed significant breed and feed main and interaction effects on albumen bitterness and a significant interaction effect on yolk bitterness. Albumen from RIR fed mixed feed and AUS fed fermented feed was higher bitterness, whereas yolk from those groups was lower bitterness. Significant breed effects were detected in four albumen amino acid traits (His, Met, Ile, and Lys) and a yolk His, whereas significant feed effects were found in 15 albumen amino acid traits (Asp, Glu, Ser, His, Gly, Thr, Ala, Tyr, Val, Met, Trp, Ile, Leu, Lys, and Pro) and a yolk cystine trait. Compared to albumen amino acids, yolk amino acids had limited effects by breed and feed. The present results suggest that genetic and nutritional factors can alter not only amino acid contents but also sensor values of bitterness, indicating that selecting the combination of breed and feed enable us to make amino acids enriched and taste added designer eggs in future.Severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome/toxic epidermal necrolysis and drug-induced hypersensitivity syndrome, are rare and occasionally fatal. However, it is difficult to detect SCARs at the drug development stage, necessitating a new approach for prediction. Therefore, in this study, using the chemical structure information of SCAR-causative drugs from the Japanese Adverse Drug Event Report (JADER) database, we tried to develop a predictive classification model of SCAR through deep learning. In the JADER database from 2004 to 2017, we defined 185 SCAR-positive drugs and 195 SCAR-negative drugs using proportional reporting ratios as the signal detection method, and the total number of reports. These SCAR-positive and SCAR-negative drugs were randomly divided into the training dataset for model construction and the test dataset for evaluation. The model performance was evaluated in the independent test dataset inside the applicability domain (AD), which is the chemical space for reliable prediction results. Using the deep learning model with molecular descriptors as the drug structure information, the area under the curve was 0.76 for the 148 drugs of the test dataset inside the AD. The method developed in the present study allows for utilizing the JADER database for SCAR classification, with potential to improve screening efficiency in the development of new drugs. This method may also help to noninvasively identify the causative drug, and help assess the causality between drugs and SCARs in postmarketing surveillance.Fine needle aspiration (FNA) cytology is an important tool for diagnosing salivary gland neoplasms and for guiding clinical management. The classic adenoid cystic carcinoma (AdCC) is a basaloid neoplasm with abundant extracellular matrix. The presence globules of extracellular matrix are quite characteristic of AdCC but not diagnostic. We selected from our files six FNA cases that contained at least some globules of amorphous matrix that are similar to the ones seen in AdCC. The aim of this case-based review is to discuss the pitfalls and some of the common differential diagnoses of AdCC in FNA cytology. By the end of this review, we hope to have shared with the readers the lessons we learned from these cases and to highlight the key criteria needed to make a correct diagnosis of AdCC based on cytomorphology. The importance of considering other entities, in addition to AdCC, whenever a salivary gland FNA presents with globules is emphasized.

    To detect ultrasonographic inflammatory signs in the lacrimal, parotid, and submandibular glands in cosmetic fillers (CFs) users.

    A prospective and cross-sectional ultrasound study of the glands in cases with CFs was performed. The sample included users of hyaluronic acid, silicone oil, polymethylmethacrylate, polycaprolactone, calcium hydroxyapatite, and polyacrylamide. Abnormalities of the parenchyma and hypervascularity signs of the glands were compared with a control group (n = 10), evaluated by 2 observers, and correlated with the type, number, and location of the facial CFs. Cohen’s kappa test and logistic regression models with odds ratios (OR) adjusted by age with 95% CI were performed.

    Sixty-three patients with CFs met the criteria. Parotid and submandibular glands had the highest percentage of parenchymal involvement 87.3 and 88.9%, respectively (p <.01). Abnormalities of the echostructure of the parenchyma and hypervascularity of the glands were detected with all kinds of fillers without significant differences per type. A significant substantial interrater kappa (0.61) with an agreement of 90% for all glands among observers was found.

    Users of common types of CFs frequently present subclinical ultrasonographic signs of inflammation of the lacrimal, parotid, and submandibular glands. Further research on the topic seems necessary.

    Users of common types of CFs frequently present subclinical ultrasonographic signs of inflammation of the lacrimal, parotid, and submandibular glands. Further research on the topic seems necessary.

    Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes and is associated with adipokines. The C1q tumor necrosis factor-related protein 9 (CTRP9) is a newly discovered adipokine. This study aimed to evaluate the association of serum CTRP9 levels with the prevalence and severity of CAN in patients with type 2 diabetes mellitus.

    We enrolled 262 patients (aged ≥18years) with type 2 diabetes mellitus into this study. Standard cardiovascular autonomic reflex tests (CARTs) were used to assess CAN and patients were divided into three groups accordingly a non-CAN group, an early CAN group, and a definite CAN group. Serum CTRP9 levels were measured by enzyme-linked immunosorbent assay, and the tertiles were calculated.

    Serum CTRP9 levels decreased significantly in the early CAN and definite CAN groups (P<0.05). The percentage of definite CAN was the highest at the minimum tertile of serum CTRP9 level (T1; P<0.05). Additionally, serum CTRP9 levels were negatively correlated with age, DM duration, hemoglobin A1c (HbA1c), and fasting plasma glucose (FPG) while positively correlated with high-density lipoprotein cholesterol (HDL; P<0.05). The level of CTRP9 was also significantly associated with the four indexes of CARTs (P<0.05). Furthermore, CTRP9 was a protective factor for definite CAN (P<0.05). Compared with the maximum tertile (T3) of the serum CTRP9 levels, a decreased level of serum CTRP9 in T1 significantly increased the prevalence ratio of definite CAN in patients with type 2 diabetes mellitus (P<0.05).

    Serum CTRP9 levels were independently associated with definite CAN. CTRP9 represents a reliable biomarker for exploring CAN in patients with type 2 diabetes mellitus.

    Serum CTRP9 levels were independently associated with definite CAN. CTRP9 represents a reliable biomarker for exploring CAN in patients with type 2 diabetes mellitus.

    Executive functions play a fundamental role in walking by integrating information from cognitive-motor pathways. Subtle changes in brain and behavior may help identify older adults who are more susceptible to executive function deficits with advancing age due to prefrontal cortex deterioration. This study aims to examine how older adults mitigate executive demands while walking during cognitively demanding tasks.

    Twenty healthy older adults (M=71.8years, SD=6.4) performed simple reaction time (SRT), go/no-go (GNG), n-back (NBK), and double number sequence (DNS) cognitive tasks of increasing difficulty while walking (i.e., dual task). Functional near infra-red spectroscopy (fNIRS) was used to measure the hemodynamic response (i.e., oxy- [HbO2] and deoxyhemoglobin [HbR]) changes in the prefrontal cortex (PFC) during dual and single tasks (i.e., walking alone). In addition, performance was measured using gait speed (m/s), response time (s), and accuracy (% correct).

    Using repeated measures ANOVAs, neural fhy older adult sample might mitigate executive demands using an automatic locomotor control strategy such that shifting conscious attention away from walking during the dual tasks resulted in decreased ∆HbO2 and ∆HbR. However, decreased prefrontal activation was inefficient at maintaining response time and accuracy performance and may be differently affected by increasing cognitive demands.

    Most of acute pancreatitis (AP) are mild and self-limiting, however, 15%-20% of patients develop severe acute pancreatitis (SAP) or moderately acute pancreatitis (MSAP) with local or systemic complications. Infection complications (ICs) result in 40%-70% morbidity and high mortality rates among SAP and MSAP patients. It is more important to early recognize of ICs of MSAP or SAP. Several studies have indicated that serum soluble programmed cell death protein (sPD-1) or programmed cell death 1 ligand (sPD-L1) levels were higher in patients with severe sepsis than in healthy volunteers and have a predictive capacity for mortality. However, the role of serum sPD-1/sPD-L1 in AP remains unclear. This study aimed to investigate whether the ICs of AP patients is associated with their sPD-1 and sPD-L1 levels, which were determined via enzyme-linked immunosorbent assay of peripheral blood samples from 63 MSAP and SAP patients and 30 healthy volunteers.

    The serum sPD-1 levels in AP patients on Days 1, 3, and 10 afte be an independent risk factor for predicting ICs in AP patients.The molecular basis for adaptations to extreme environments can now be understood by interrogating the ever-increasing number of sequenced genomes. Mammals such as cetaceans, bats, and highland species can protect themselves from oxidative stress, a disruption in the balance of reactive oxygen species, which results in oxidative injury and cell damage. Here, we consider the evolution of the glutathione peroxidase (GPX) family of antioxidant enzymes by interrogating publicly available genome data from 70 mammalian species from all major clades. We identified 8 GPX subclasses ubiquitous to all mammalian groups. Mammalian GPX gene families resolved into the GPX4/7/8 and GPX1/2/3/5/6 groups and are characterized by several instances of gene duplication and loss, indicating a dynamic process of gene birth and death in mammals. Seven of the eight GPX subfamilies (all but GPX7) were under positive selection, with the residues under selection located at or close to active sites or at the dimer interface. We also reveal evidence of a correlation between ecological niches (e.g. high oxidative stress) and the divergent selection and gene copy number of GPX subclasses. Notably, a convergent expansion of GPX1 was observed in several independent lineages of mammals under oxidative stress and may be important for avoiding oxidative damage. Collectively, this study suggests that the GPX gene family has shaped the adaption of mammals to stressful environments.Wnt-Fzd signalling pathway plays a critical role in acute myeloid leukaemia (AML) progression and oncogenicity. There is no study to investigate the prognostic value of Wnt and Fzd gene families in AML. Our study screened 84 AML patients receiving chemotherapy only and 71 also undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) from the Cancer Genome Atlas (TCGA) database. We found that some Wnt and Fzd genes had significant positive correlations. The expression levels of Fzd gene family were independent of survival in AML patients. In the chemotherapy group, AML patients with high Wnt2B or Wnt11 expression had significantly shorter event-free survival (EFS) and overall survival (OS); high Wnt10A expressers had significantly longer OS than the low expressers (all P less then .05), whereas, in the allo-HSCT group, the expression levels of Wnt gene family were independent of survival. We further found that high expression of Wnt10A and Wnt11 had independent prognostic value, and the patients with high Wnt10A and low Wnt11 expression had the longest EFS and OS in the chemotherapy group. Pathway enrichment analysis showed that genes related to Wnt10A, Wnt11 and Wnt 2B were mainly enriched in 'cell morphogenesis involved in differentiation’, 'haematopoietic cell lineage’, 'platelet activation, signalling and aggregation’ and 'mitochondrial RNA metabolic process’ signalling pathways. Our results indicate that high Wnt2B and Wnt11 expression predict poor prognosis, and high Wnt10A expression predicts favourable prognosis in AML, but their prognostic effects could be neutralized by allo-HSCT. Combined Wnt10A and Wnt11 may be a novel prognostic marker in AML.

    Common sinonasal disorders include chronic rhinosinusitis (CRS), allergic rhinitis (AR), and a deviated nasal septum (DNS), which often coexist with shared common symptoms including nasal obstruction, olfactory dysfunction, and rhinorrhea. Various objective outcome measures and patient-reported outcome measures (PROMs) are used to assess disease severity; however, there is limited evidence in the literature on the correlation between them. This systematic review aims to examine the relationship between them and provide recommendations.

    A search of MEDLINE and EMBASE identified studies quantifying correlations between objective outcome measures and PROMs for the sinonasal conditions using a narrative synthesis.

    In total, 59 studies met inclusion criteria. For nasal obstruction, rhinomanometry shows a lack of correlation whereas peak nasal inspiratory flow (PNIF) shows the strongest correlation with PROMs (r > 0.5). The Sniffin’ Stick test shows a stronger correlation with PROMs (r > 0.5) than the UNIF should be used in routine clinical practice for nasal obstruction; rhinomanometry and acoustic rhinometry may be useful in research. The Sniffin’ Sticks test is recommended for olfactory dysfunction with UPSIT as an alternative. CT scores should be excluded as a routine CRS outcome measure, and endoscopic scores should be used in combination with PROMs until further research is conducted.Breast cancer continues to be a serious public health problem. The role of the hedgehog pathway in normal development of the mammary gland as well as in carcinogenesis and progression of breast cancer is the subject of intense investigation, revealing functional interactions with cell surface heparan sulfate. Nevertheless, its influence on breast cancer prognosis, and its relation to specific sulfation motifs in heparan sulfate have only been poorly studied in large patient cohorts. Using the public database KMplotter that includes gene expression and survival data of 3951 patients, we found that the higher expression of SHH, HHAT, PTCH1, GLI1, GLI2, and GLI3 positively influences breast cancer prognosis. Stratifying patients according to the expression of hormone receptors, histological grade, lymph node metastasis, and systemic therapy, we observed that GLI1, GLI2, and GLI3 expression, as well as co-expression of SHH and ELP1 were associated with worse relapse-free survival in patients with HER2-positive tugarding a therapeutical targeting of the hedgehog pathway in breast cancer.

    Heart transplantation (HTx) results in complete autonomic denervation of the donor heart, causing resting tachycardia and abnormal heart rate (HR) responses to exercise. We determined the time course of suggestive cardiac reinnervation post HTx and investigated its clinical significance.

    Heart rate kinetics during standard cardiopulmonary exercise testing at 2.5-5years after HTx was assessed in 58 patients. According to their HR increase 30s after exercise onset, HTx recipients were classified as denervated (slow responders <5beats per minute [b.p.m.]) or potentially reinnervated (fast responders ≥5b.p.m.). Additionally, in 30 patients, longitudinal changes of maximal oxygen consumption and HR kinetics were assessed during the first 15 post-operative years. At 2.5-5years post HTx, 38% of our study population was potentially reinnervated. Fast responders were significantly younger (41±15years) than slow responders (53±13years, P=0.003) but did not differ with regard to donor age, immunosuppressive regime, cardiovascular risk factors, endomyocardial biopsy, or vasculopathy parameters. While HR reserve (56±20 vs. 39±15b.p.m., P=0.002) and HR recovery after 60s (15±11 vs. 5±6b.p.m., P<0.001) were greater in fast responders, resting HR, peak HR of predicted, and peak oxygen consumption of predicted were comparable.

    Signs of reinnervation occurred mainly in younger patients. Maximal oxygen consumption was independent of HR kinetics.

    Signs of reinnervation occurred mainly in younger patients. Maximal oxygen consumption was independent of HR kinetics.

    Immunotherapy agents are used to treat advanced head and neck lesions. We aim to elucidate relationship between immunotherapy and surgical wound complications.

    Retrospective multi-institutional case series evaluating patients undergoing ablative and flap reconstructive surgery and immunotherapy treatment.

    wound complications.

    Eight-two (62%) patients received preoperative therapy, 89 (67%) postoperative, and 33 (25%) in both settings. Forty-one (31%) patients had recipient site complications, 12 (9%) had donor site. Nineteen (14%) had major recipient site complications, 22 (17%) had minor. There was no statistically significant difference in complications based on patient or tumor-specific variables. Preoperative therapy alone demonstrated increased major complications (odds ratio [OR] 3.7, p = 0.04), and trend to more donor site complications (OR 7.4, p = 0.06), however treatment in both preoperative and postoperative therapy was not.

    Preoperative immunotherapy may be associated with increased wound complications. Controlled studies are necessary to delineate this association and potential risks of therapy.

    Preoperative immunotherapy may be associated with increased wound complications. Controlled studies are necessary to delineate this association and potential risks of therapy.

    To evaluate henagliflozin, a novel sodium-glucose co-transporter-2 inhibitor, as monotherapy in patients with type 2 diabetes and inadequate glycaemic control with diet and exercise.

    This multicentre trial included a 24-week, randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. Four hundred and sixty-eight patients with an HbA1c of 7.0%-10.5% were randomly assigned (111) to receive once-daily placebo, or 5 or 10 mg henagliflozin. After 24 weeks, patients on placebo were switched to 5 or 10 mg henagliflozin, and patients on henagliflozin maintained the initial therapy. The primary endpoint was the change in HbA1c from baseline after 24 weeks.

    At Week 24, the placebo-adjusted least squares (LS) mean changes from baseline in HbA1c were -0.91% (95% CI -1.11% to -0.72%; P < .001) and -0.94% (-1.13% to -0.75%; P < .001) with henagliflozin 5 and 10 mg, respectively; the placebo-adjusted LS mean changes were -1.3 (-1.8 to -0.9) and -1.5 (-2.0 to -1.1) kg in body weight, and -5.1 (-7.2 to -3.0) and -4.4 (-6.5 to -2.3) mmHg in systolic blood pressure (all P < .05). The trends of these improvements were sustained for an additional 28 weeks. Adverse events occurred in 81.0%, 78.9% and 78.9% of patients in the placebo, henagliflozin 5 and 10 mg groups, respectively. No diabetic ketoacidosis or major episodes of hypoglycaemia occurred.

    Henagliflozin 5 mg and 10 mg as monotherapy provided effective glycaemic control, reduced body weight and blood pressure, and was generally well tolerated.

    Henagliflozin 5 mg and 10 mg as monotherapy provided effective glycaemic control, reduced body weight and blood pressure, and was generally well tolerated.

    To determine usefulness of the „speckle sign” in the diagnosis of deep invasive endometriosis.

    This HIPAA-compliant, institutional review board-approved retrospective study with informed consent waived included 25 women (mean age 20-69 years) with histopathologically confirmed posterior cul-de-sac endometriosis between 2013 and 2018. Transvaginal ultrasound exams of these patients were reviewed by 2 expert radiologists searching for the „speckle sign,” defined as irregular obliteration of the posterior cul-de-sac and bright (hyperechoic) internal echoes. The frequency of additional findings such as „kissing ovaries,” endometriomas in the adnexa, bowel tethering in the posterior pelvic compartment, retroflexed uterus, adenomyosis, and pelvic free fluid were also analyzed. Data regarding clinical features, histopathologic findings and management were collected through a review of the medical record.

    Reader one identified posterior compartment endometriosis in 20/25 patients, and reader two in 22/25 patients, with 96% agreement. Adnexal endometriomas were found in 21/25 patients for both readers (k = 0.70) and were bilateral in 23% of patients. The ovaries were adherent to each other in the midline („kissing ovaries”) in 50% of patients; the bowel was tethered anteriorly in 20%; the presence of adenomyosis was seen in about 27%, and a retroflexed uterus was seen in 24% of patients.

    The speckle sign could be helpful in making the diagnosis of posterior compartment endometriosis, and the sign is often found in conjunction with other imaging features of endometriosis.

    The speckle sign could be helpful in making the diagnosis of posterior compartment endometriosis, and the sign is often found in conjunction with other imaging features of endometriosis.Carbohydrate purification remains problematic due to the intrinsic diversity of structural isomers present in nature. Although liquid chromatography-based techniques are suitable for analyzing or preparing most glycan structures acquired either from natural sources or through chemical or enzymatic synthesis, the separation of regioisomers or linkage isomers with a clear resolution remains challenging. Herein, a carbon dioxide supercritical fluid chromatography (SFC) method was devised to resolve 18 human milk glycosides oligomers (disaccharides to hexasaccharides), fucosylated regioisomers (lacto-N-fucopentaose I, III, and V; lacto-N-neofucopentaose V; lacto-N-difucohexaose III; blood group H1 antigen; and TF-LNnT), and connectivity isomers (lacto-N-tetraose/lacto-N-neotetraose and para-lacto-N-hexaose/para-lacto-N-neohexaose/type-1 hexasaccharide). The analysis of these glycosides represents a major limitation associated with conventional carbohydrate analysis. The unprecedented resolution achieved by the SFC method indicates the suitability of this key technology for revealing complex human milk glycomes.Epilepsy is a common brain disorder, repeated seizures of epilepsy may lead to a series of brain pathological changes such as neuronal or glial damage. However, whether circular RNAs are involved in neuronal injury during epilepsy is not fully understood. Here, we screened circIgf1r in the status epilepticus model through circRNA sequencing, and found that it was upregulated after the status epilepticus model through QPCR analysis. Astrocytes polarizing toward neurotoxic A1 phenotype and neurons loss were observed after status epilepticus. Through injecting circIgf1r siRNA into the lateral ventricle, it was found that knocking down circIgf1r in vivo would induce the polarization of astrocytes to phenotype A2 and reduce neuronal loss. The results in vitro further confirmed that inhibiting the expression of circIgf1r in astrocytes could protect neurons by converting reactive astrocytes from A1 to the protective A2. In addition, knocking down circIgf1r in astrocytes could functionally promote astrocyte autophagy and relieve the destruction of 4-AP-induced autophagy flux. In terms of mechanism, circIgf1r promoted the polarization of astrocytes to phenotype A1 by inhibiting autophagy. Taken together, our results reveal circIgf1r may serve as a potential target for the prevention and treatment of neuron damage after epilepsy.Mechanochromic elastomers that exhibit force-induced cross-linking reactions in the bulk state are introduced. The synthesis of segmented polyurethanes (SPUs) that contain difluorenylsuccinonitrile (DFSN) moieties in the main chain and methacryloyl groups in the side chains was carried out. DFSN was selected as the mechanophore because it dissociates under mechanical stimuli to form pink cyanofluorene (CF) radicals, which can also initiate the radical polymerization of methacrylate monomers. The obtained elastomers generated CF radicals and changed color by compression or extension; they also became insoluble due to the mechanically induced cross-linking reactions. Additionally, an SPU containing diphenylmethane units also exhibited highly sensitive mechanofluorescence. To the best of our knowledge, this is the first report to demonstrate damage detection ability and changes in the mechanical properties of bulk elastomers induced by simple compression or extension.

    Headache is an important manifestation during SARS-CoV-2 infection. In this study, the aim was to identify factors associated with headache in COVID-19 and headache characteristics.

    This case-control study includes COVID-19 hospitalized patients with pneumonia during March 2020. Controls comprise COVID-19 patients without headache and the cases are COVID-19 patients with headache. Demographic, clinical and laboratory data were obtained from the medical records. Headache characteristics were evaluated by semi-structured telephonic interview after discharge.

    Of a total of 379 COVID-19 patients, 48 (13%) developed headache. Amongst these, 30 (62%) were men and the median age was 57.9 (47-73) years. Headache was associated with younger age, fewer comorbidities and reduced mortality, as well as with low levels of C-reactive protein, mild acute respiratory distress syndrome and oropharyngeal symptoms. A logistic multiple regression model revealed that headache was directly associated with D-dimer and creatini to systemic viral infection. Further research addressing the underlying mechanisms to confirm these findings is warranted.Periosteal expansion osteogenesis (PEO) results in the formation of new bone in the gap between periosteum and original bone. The purpose of this study is to evaluate the use of a polyethylene terephthalate (PET) membrane as an activation device. A dome-shaped PET membrane coated with hydroxyapatite/gelatin on the inner side was inserted between the elevated periosteum and bone at the rabbit calvaria. In the experimental group, the membrane was pushed, bent, and attached to the bone surface and fixed with a titanium screw. In control group, the membrane was only inserted and fixed with titanium screw at original shape under the periosteum. After 7 days, the screw was removed and the mesh was activated in the experimental group. Three animals per group with or without setting a latency period for activation were sacrificed at 3 and 5 weeks after surgery. Bone formation was evaluated via micro-computed tomography and determined by histomorphometric methods and histological evaluation. No PET membrane-associated complications were observed during this study. The quantitative data by the area and the occupation of newly formed bone indicated that the experimental group had a higher volume of new bone than the control group at 3 weeks after surgery. Histologically, bone formation progressed to areas adjacent to the cortical perforations; many sinusoidal vessels ran from the perforations to overlying fibrous tissue via the new bone. No bone or obvious inflammatory cells were observed over the membrane. The PET membrane has biocompatible device for PEO that induces a natural osteogenic response at the gap between the original bone and periosteum.

    Androgenetic alopecia (AGA) is the most common form of alopecia in men. Cetirizine, a second-generation H1 blocker, is known for its anti-inflammatory properties and its ability to decrease prostaglandin D2 (PGD2) production.

    To evaluate the efficacy and tolerability of topical cetirizine in male patients with AGA.

    Two groups of 30 patients each (healthy males aged between 22 and 55years) with different grades of AGA classified according to the Hamilton-Norwood classification were recruited for this study. Group A subjects applied 1mL of 1% topical cetirizine daily, while group B subjects served as controls and were instructed to apply 1mL of a placebo solution for 6months.

    Dermoscopic assessment revealed significantly higher hair regrowth among the cetirizine-treated group (P<.001). The patients’ satisfaction was significantly higher among the cetirizine-treated group (P<.001).

    The current study highlights a potential role cetirizine might have in treating AGA. It should be noted that studies are lacking in this regard and more randomized and controlled trials are warranted in order to confirm or refute such early findings.

    The current study highlights a potential role cetirizine might have in treating AGA. It should be noted that studies are lacking in this regard and more randomized and controlled trials are warranted in order to confirm or refute such early findings.Despite significant evidence that Rac1 is localized to the nucleus, little is known regarding the function and biological significance of nuclear Rac1. Here, we showed that in response to EGF Rac1 was translocated to nuclear speckles and co-localized with the nuclear speckle marker Serine/arginine-rich splicing factor 2 (SRSF2) in Cos-7 cells. We also showed that the nuclear speckle localization of Rac1 was dependent on its T108 phosphorylation and facilitated by Rac1 polybasic region (PBR) that contains a nuclear localization signal and Rac1 GTPase activity. To gain insight into the function of Rac1 in nuclear speckles, we searched for Rac1 binding proteins in the nucleus. We isolated nuclear fraction of HEK 293 cells and incubated with GST-Rac1 and the phosphomimetic GST-Rac1T108E. We identified 463 proteins that were associated with GST-Rac1T108E, but not with GST-Rac1 by LC-MS/MS. Three notable groups of these proteins are the heterogeneous nuclear ribonucleoproteins (hnRNPs), small nuclear ribonucleoproteins (snRNPs), and SRSFs, all of which are involved in pre-mRNA splicing and associated with nuclear speckles. We further showed by co-immunoprecipitation that Rac1 interacts with SRSF2, hnRNPA1, and U2A’ in response to EGF. The interaction is dependent on T108 phosphorylation and facilitated by Rac1 PBR and GTPase activity. We showed that hnRNPA1 translocated in and out of nucleus in response to EGF in a similar pattern to Rac1. Rac1 only partially colocalized with U2A’ that localizes to the actual splicing sites adjacent to nuclear speckle. Finally, we showed that Rac1 regulated EGF-induced pre-mRNA splicing and this is mediated by T108 phosphorylation. We conclude that in response to EGF, T108 phosphorylated Rac1 is targeted to nuclear speckles, interacts with multiple groups of proteins involved in pre-mRNA splicing, and regulates EGF-induced pre-mRNA splicing.

    In this analysis of the EWOLUTION registry, we evaluated the incidence, relevance and predictors of device-related thrombus in a large multi-center real-world cohort undergoing LAAc with the WATCHMAN device.

    We analyzed the 835 patients who underwent percutaneous LAA closure with the WATCHMAN device in the EWOLUTION registry in whom at least one TEE follow up was performed. Patients were 74 ± 9 y/o and were at high risk for stroke and bleeding (CHA2DS2-VASC-Score 4.3 ± 1.7; HAS-BLED-Score 2.3 ± 1.2). Device-related thrombus was detected in 4.1% (34/835) after a median of 54 days (IQR 42-111 days) with 91.2% (31/34) being detected within 3 months after the procedure or at the time of first TEE. Hereby DRT occurred irrespective of postprocedural anticoagulation. Patients with DRT more frequently had long-standing, non-paroxysmal atrial fibrillation (82.4 vs. 64.9%, p < .01), evidence of dense spontaneous echo contrast (26.5 vs. 11.9%, p = .03) and larger LAA diameters at the ostium (22.8 ± 3.5 vs. 21.1 ±n most cases.

    In real-world patients undergoing LAAc with the WATCHMAN device, DRT is rare. DRT was most frequently detected within the first 3 months after LAAc regardless of post-procedural regimen and was not associated with an increased risk of stroke or SE. While long-standing atrial fibrillation was the only independent factor associated with DRT, medical treatment of DRT resulted in a resolution of thrombi in most cases.Cervical cancer is the most common gynaecological malignancy, with a high incidence rate and mortality rate in middle-aged women. Human bone marrow mesenchymal stem cells (hBMSCs) have been implicated in the initiation and subsequent development of cancer, along with the involvement of extracellular vesicles (EVs) mediating intracellular communication by delivering microRNAs (miRNAs or miRs). This study is aimed at investigating the physiological mechanisms by which EVs-encapsulated miR-144-3p derived from hBMSCs might mediate the progression of cervical cancer. The expression profiles of centrosomal protein, 55 Kd (CEP55) and miR-144-3p in cervical cancer cell lines and tissues, were quantified by RT-qPCR and Western blot analysis. The binding affinity between miR-144-3p and CEP55 was identified using in silico analysis and luciferase activity determination. Cervical cancer cells were co-cultured with EVs derived from hBMSCs that were treated with either miR-144-3p mimic or miR-144-3p inhibitor. Cervical cancer cell proliferation, invasion, migration and apoptosis were detected in vitro. The effects of hBMSCs-miR-144-3p on tumour growth were also investigated in vivo. miR-144-3p was down-regulated, whereas CEP55 was up-regulated in cervical cancer cell lines and tissues. CEP55 was targeted by miR-144-3p, which suppressed cervical cancer cell proliferation, invasion and migration and promoted apoptosis via CEP55. Furthermore, similar results were obtained by hBMSCs-derived EVs carrying miR-144-3p. In vivo assays confirmed the tumour-suppressive effects of miR-144-3p in hBMSCs-derived EVs on cervical cancer. Collectively, hBMSCs-derived EVs-loaded miR-144-3p impedes the development and progression of cervical cancer through target inhibition of CEP55, therefore providing us with a potential therapeutic target for treating cervical cancer.

    The unprecedented COVID-19 pandemic has put a serious burden on the healthcare system worldwide. Due to varied manifestations of SARS-CoV-2 infection, many scoring systems, which were earlier used for community acquired pneumonia (CAP) are in use to determine the disease severity and the need of ICU admissions for proper management. COVID-19 is a relatively new disease and the validity of these scoring systems in SARS-CoV-2 infection is not completely known. This study aimed to validate these scoring systems in cases of COVID-19 pneumonia in an Indian setup. The study has also tried to find the most accurate indicator of disease severity and 14-day mortality among these scoring systems.

    This study included 122 SARS-CoV-2 infected patients at a tertiary hospital in Ranchi, Jharkhand. The severity of the disease according to ICMR protocol for COVID-19, the PSI/PORT score, the CURB-65 score and the SCAP score were calculated in all the patients and analysed with the disease outcome, that is, 14-day mortality.

    SCAP score, PSI/PORT score and CURB-65 criteria, all were good indicators of disease severity and 14-day mortality. However, when compared to other scoring systems, SCAP score was a more accurate marker of disease severity and 14-day mortality.

    The PSI/PORT scoring system, the CURB-65 criteria and the SCAP scoring system can be used to assess the COVID-19 severity and predict the 14-day mortality risk in cases of COVID-19 pneumonia.

    The PSI/PORT scoring system, the CURB-65 criteria and the SCAP scoring system can be used to assess the COVID-19 severity and predict the 14-day mortality risk in cases of COVID-19 pneumonia.

    This randomized clinical trial aimed to compare the outcomes of the mandibular overdenture retained by one (1-IOD) or two (2-IOD) implants.

    Participants received new complete dentures, were assessed at baseline and randomly assigned to groups. Early loaded single midline implant (1-IOD) or two implants in the canine regions bilaterally (2-IOD). Ball attachments were used for overdenture retention. Post-treatment outcomes (6- and 12-month follow-ups) included patient satisfaction, oral health-related quality of life measures, and chewing function. Data analysis included within- and between-group comparisons, and Generalized Estimating Equations. Both superiority and non-inferiority hypotheses were tested.

    Forty-seven participants were included (1-IOD=23; 2-IOD=24). Significant improvements in OHIP-Edent were observed after insertion of new dentures and at the 1-year follow-up compared with baseline. No differences were found between the 1- and 2-IOD groups for the OHIP-Edent and QoLFAST scores. Patient satisfaction with the mandibular denture improved significantly from baseline to the 6-month follow-up and remained unaltered until 1year, with no differences between groups. The magnitudes of treatment effect sizes were moderate to large for patient-reported outcomes. Progressive improvement in chewing function occurred in both groups. Non-inferiority testing based on a 15% non-inferiority margin showed inconclusive results for patient-reported outcomes, whilst chewing function in the 1-IOD group was concluded to be not inferior to the 2-IOD group.

    Results support the use of both 1- and 2-IOD. The 1-IOD was also an acceptable alternative to the 2-IOD as a secondary option for the treatment of the edentulous mandible.

    Results support the use of both 1- and 2-IOD. The 1-IOD was also an acceptable alternative to the 2-IOD as a secondary option for the treatment of the edentulous mandible.To elucidate the contributions of specific lipid species to metabolic traits, we integrated global hepatic lipid data with other omics measures and genetic data from a cohort of about 100 diverse inbred strains of mice fed a high-fat/high-sucrose diet for 8 weeks. Association mapping, correlation, structure analyses, and network modeling revealed pathways and genes underlying these interactions. In particular, our studies lead to the identification of Ifi203 and Map2k6 as regulators of hepatic phosphatidylcholine homeostasis and triacylglycerol accumulation, respectively. Our analyses highlight mechanisms for how genetic variation in hepatic lipidome can be linked to physiological and molecular phenotypes, such as microbiota composition.High ambient temperature is one of the major causes of economic losses in the livestock industry. The poultry industry is an integral part of the livestock industry. It faces severe losses due to heat stress (HS). The adverse effects of HS can be seen on production performance, body temperature, intestinal health, appetite hormone regulation, immune responses and oxidative characteristics. It is important to monitor these parameters to identify the HS possessions during rearing so that timely action can be taken to minimize the adverse effects of high ambient temperature. Furthermore, the application of productive methods on farms is equally important. Several strategies have been suggested by researchers. Providing a suitable environment with selective rearing systems along with proper ventilation and hygiene is the basic requirement for all types of livestock reared for animal protein. Supplementation of appropriate feed additive could be useful for improving intestinal absorption and minimizing adverse effects of HS. Selection for breeding heat resistant birds also provide merits for improving the germplasm of the strains. Early age thermal conditioning also helps in developing resistance for HS. The most recent advancement is the supplementation of active substances during incubation. It is expected that these methods may have a potential impact on the poultry industry for creating thermotolerance in the newly hatched chicks. This review highlights the major issues concerning chicken health and suggests the measures to be adopted following the increase in environmental temperature.

    LMR-101 is a bisphenol derivative of propofol, a short-acting general anesthetic, which is also used to manage status epilepticus (SE). We evaluated the sedative and anticonvulsant effects of LMR-101 to discover its potential to manage epilepsy and SE in the clinic.

    Comparative studies between LMR-101 and propofol were performed in mice to elucidate an appropriate dose range for LMR-101 that produced anticonvulsant effects without significant sedation. Then, the anticonvulsive efficacy for LMR-101 was evaluated using seizure models induced by pentylenetetrazol and (+)-bicuculline. The ability of LMR-101 to inhibit SE was assessed using a rat model of SE induced by pilocarpine. Radioligand binding assay profiles for LMR-101 were performed to evaluate the potential mechanisms of action underlying its anticonvulsant properties.

    In the mouse study, LMR-101 exhibited greater anticonvulsant and lesser sedative effect compared with propofol. LMR-101 completely inhibited pentylenetetrazol-induced seizures at a dy of the mechanisms of action of LMR-101 would be of considerable value in the search for new active drug sites on GABA

    receptors.

    It is anticipated that LMR-101 might play an essential role in the clinical management of epilepsy and SE. LMR-101 also might bind to a novel target site on the GABAA receptor that is different from existing antiepileptic drugs. Further study of the mechanisms of action of LMR-101 would be of considerable value in the search for new active drug sites on GABAA receptors.

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