Donepezil treatment protected rats from renal dysfunction in a dose-dependent manner and through the cholinergic anti-inflammatory pathway. Additionally, donepezil significantly reduced tubular damages, prevented neutrophil infiltration and decreased productions of the IL-6, TNF-α, nitric oxide content and oxidative damage.

These data indicate that donepezil exerts a protective anti-inflammatory effect during ARF through the cholinergic pathway and Nitric oxide pathway. In addition, this study could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation and other injury.

These data indicate that donepezil exerts a protective anti-inflammatory effect during ARF through the cholinergic pathway and Nitric oxide pathway. In addition, this study could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation and other injury.Introduction Hand, foot, and mouth disease caused by enterovirus A71 (EV-A71) is more frequently associated with neurological complications and deaths compared to other enteroviruses. Areas covered The authors discuss current understanding of the neuropathogenesis of EV-A71 based on various clinical, human, and animal model studies. The authors discuss the important advancements in virus entry, virus dissemination, and neuroinvasion. The authors highlight the role of host immune system, host genetic factors, viral quasispecies, and heparan sulfate in EV-A71 neuropathogenesis. Expert opinion Comparison of EV-A71 with EV-D68 and PV shows similarity in primary target sites and dissemination to the central nervous system. More research is needed to understand cellular tropisms, persistence of EV-A71, and other possible invasion routes. EV-A71 infection has varied clinical manifestations which may be attributed to multiple receptors usage. Future development of antivirals and vaccines should target neurotropic enteroviruses. Repurposing drug and immunomodulators used in combination could reduce the severity of EV-A71 infection. Only a few drugs have been tested in clinical trials, and in the absence of antiviral and vaccines (except China), active virus surveillance, good hand hygiene, and physical distancing should be advocated. A better understanding of EV-A71 neuropathogenesis is critical for antiviral and multivalent vaccines development.

Although it is reported that patients with coronavirus disease 2019 (COVID-19) disease who have comorbidities are at higher risk to suffer adverse clinical outcomes, there are inadequate evidence to clarify the association between COVID-19 and asthma. On this ground, this study aims to systematically analyze the clinical characteristics of COVID-19 patients with asthma.

In this single-center, retrospective and observational cohort study, 21 COVID-19 patients with asthma and 100 non-asthma COVID-19 patients were statistically matched by propensity score based on age, sex and comorbidities. Meanwhile, a collection and comparison concerning demographic indicators, clinical and laboratory examinations, treatments and outcomes were conducted between two groups to specify their differences.

Statistically, the COVID-19 patients with asthma had a higher proportion of ICU admission (14.3% [3/21] vs. 2.1% [2/96]

 = 0.040) than those who do not have. On top this, a higher level of inflammatory responses, such as interleukin 6, interleukin 8, procalcitonin, leukocytes, neutrophils and CD4

T cells was presented in asthma patients. Moreover, the increase of organ damage indices like D-dimer, lactate dehydrogenase and high-sensitivity cardiac troponin I, were more pronounced in COVID-19 patients with asthma.

Exacerbated inflammatory responses and multiple organ damages were triggered in COVID-19 patients with asthma, which highlights more intensive surveillance and supportive treatment.

Exacerbated inflammatory responses and multiple organ damages were triggered in COVID-19 patients with asthma, which highlights more intensive surveillance and supportive treatment.Introduction This review aims to summarize current progress of the last ten years in the development of biomarkers used for classifying the immune response of the septic host and for monitoring the efficacy of the applied adjunctive immunotherapy.Areas covered An extensive search of the literature was performed. In this review the authors discuss available biomarkers of host immune response in sepsis toward two directions; immunosuppression and hyperinflammation. Ferritin, sCD163, sIL-2 ra, and IL-18 may help in the diagnosis of macrophage activation syndrome (MAS) complicating sepsis whereas lymphopenia, decreased HLA-DR expression on monocytes, overexpression of Programmed cell death protein-1 (PD-1)/Programmed death-ligand 1 (PD-L1) and IL-10 are indicators of sepsis-induced immunosuppression. Novel approaches in the classification of immune state in sepsis include Myeloid-Derived Suppressor Cells (MDSC) and specific endotypes, defined by gene expression and molecular techniques.Expert opinion HLA-DR and ferritin are the most commonly used biomarkers to monitor immunomodulation in clinical practice whereas developing specific sepsis endotypes is the future target. New immunotherapy trials in sepsis need to incorporate biomarkers for a personalized treatment.Proteins are oxidatively modified by a large number of reactive species including reactive oxygen species, lipid peroxidation-derived aldehydes, and reducing sugars. Among divergent oxidative modifications, introduction of carbonyl groups such as aldehyde, ketone, and lactam into the amino acid side chains of proteins is a major hallmark for oxidative damage to proteins, and is termed „protein carbonylation”. Detection and quantification of protein carbonyls is commonly performed to determine the level of oxidative stress in the context of cellular damage, aging and several age-related disorders. This review focuses on the molecular mechanisms and biological implications of protein carbonylation, and also presents current analytical approaches for determining and characterizing carbonylated proteins.

Microsatellite instability-high (MSI-H) colorectal cancer (CRC) represents a unique subset of CRC characterized by elevated neoantigen expression and a high degree of intraepithelial T-cell infiltrate. These characteristics make MSI-H tumors particularly susceptible to immune checkpoint inhibitors (ICIs) such as pembrolizumab which inhibit the negative regulation of cytotoxic T-cells and promote T-cell mediated anti-tumor activity.

We discuss the drug development of pembrolizumab including the seminal studies which enabled the drug to garner FDA approvals in the refractory and first-line settings for patients with MSI-H CRC, the pharmacokinetic & pharmacodynamic profile of the agent, and the adverse event profile of the ICI. We also discuss unmet needs in the arena of ICIs including strategies to overcome tumor resistance and to increase the applicability of the agents to a broader population of CRC patients.

Despite the anti-tumor activity of pembrolizumab in patients with MSI-H CRC, 30-35% of patients fail to derive any benefit. Ongoing research efforts are seeking to identify ICI combinations, which can overcome CRC resistance to pembrolizumab, move ICIs into the treatment paradigm for patients with localized MSI-H CRC and enable ICIs to become meaningful treatment options for patients with microsatellite stable CRC.

Despite the anti-tumor activity of pembrolizumab in patients with MSI-H CRC, 30-35% of patients fail to derive any benefit. Ongoing research efforts are seeking to identify ICI combinations, which can overcome CRC resistance to pembrolizumab, move ICIs into the treatment paradigm for patients with localized MSI-H CRC and enable ICIs to become meaningful treatment options for patients with microsatellite stable CRC.Background The comorbidities and clinical signs of coronavirus disease 2019 (COVID-19) patients have been reported mainly as descriptive statistics, rather than quantitative analysis even in very large investigations. The aim of this study was to identify specific patients’ characteristics that may modulate COVID-19 hospitalization risk.Research design and methods A pooled analysis was performed on high-quality epidemiological studies to quantify the prevalence (%) of comorbidities and clinical signs in hospitalized COVID-19 patients. Pooled data were used to calculate the relative risk (RR) of specific comorbidities by matching the frequency of comorbidities in hospitalized COVID-19 patients with those of general population.Results The most frequent comorbidities were hypertension, diabetes mellitus, and cardiovascular and/or cerebrovascular diseases. The RR of COVID-19 hospitalization was significantly (P less then 0.05) reduced in patients with asthma (0.86, 0.77-0.97) or chronic obstructive pulmonary disease (COPD) (0.46, 0.40-0.52). The most frequent clinical signs were fever and cough.Conclusion The clinical signs of hospitalized COVID-19 patients are similar to those of other infective diseases. Patients with asthma or COPD were at lower hospitalization risk. This paradoxical evidence could be related with the protective effect of inhaled corticosteroids that are administered worldwide to most asthmatic and COPD patients.Objectives Postmenopausal osteoporosis carries a high risk of fractures, which decrease quality of life and are associated with high morbidity, mortality, and economic burden. The best pharmacological treatment options to manage and prevent osteoporotic fractures remain still unclear. The present study investigated the efficacy and safety of the most commonly employed drugs in the management of postmenopausal osteoporosis. Methods Only RCTs comparing different drugs for the management of postmenopausal osteoporosis were included. Data from 76 RCTs (205,011 patients) were collected. The mean follow-up was 27.6 ± 14.9 months. Results Denosumab reported the lowest rate of non-vertebral fractures (LOR -1.57), Romosozumab the lowest rate of vertebral fractures (LOR 1.99), and Ibandronate the lowest rate of hip fractures (LOR0.18). Serious adverse events resulted in the lowest in the Raloxifene group (LOR 3.11), while those leading to study discontinuation were lowest in the Romosozumab cohort (LOR 2.65). Conclusions Denosumab resulted in most effective, particularly in reducing the occurrence of non-vertebral fractures. Romosozumab and Ibandronate resulted best to prevent, respectively, vertebral fractures and hip fractures. Adverse events leading to study discontinuation were less frequent in the Romosozumab and Denosumab groups, while Raloxifene and Alendronate showed a lower incidence of serious adverse events overall. Level of evidence I, Bayesian network meta-analysis of RCTs.

Women with a successful vaginal birth after cesarean delivery (VBAC) have less morbidity than women undergoing repeat cesarean delivery. Although several scores and models predict VBAC success, none focus on pregnant women with pre-labor rupture of membranes (PROM). We evaluated different clinical variables that might predict the likelihood of VBAC success in women with PROM.

A retrospective, 5-year study in a large referral center from December 2013 to December 2018. Inclusion criteria were women with singleton pregnancy, at or beyond 37 weeks’ gestation, admitted with spontaneous PROM, with one previous cesarean delivery that consented trial of labor. Exclusion criteria were history of two cesarean deliveries, multiple gestations or obstetrical contraindications for TOLAC, including maternal request for repeat cesarean delivery. Variables associated with successful VBA C were identified using multivariate logistic regression.

Of 302 women in the cohort, 74.8% (226/302) delivered vaginally (successful e of contraindications, a fair trial of labor after cesarean delivery is justified.

Women with spontaneous pre-labor PROM and previous cesarean delivery have high success rates of VBAC. The only significant variable associated with successful TOLAC in women with spontaneous PROM at term was the duration of PROM-to-delivery time. Our findings suggest that the success rate of VBAC is likely multifactorial, not-necessarily related to a specific underlying factor, and in the absence of contraindications, a fair trial of labor after cesarean delivery is justified.Introduction Cyclin-dependent kinase 7 (CDK7) is a part of the CDK-activating kinase family (CAK) which has a key role in the cell cycle and transcriptional regulation. Several lines of evidence suggest that CDK7 is a promising therapeutic target for cancer. CDK7 selective inhibitors such as SY-5609 and CT7001 are in clinical development. Areas covered We explore the biology of CDK7 and its role in cancer and follow this with an evaluation of the preclinical and clinical progress of CDK7 inhibitors, and their potential in the clinic. We searched PubMed and ClinicalTrials to identify relevant data from the database inception to 14 October 2020. Expert opinion CDK7 inhibitors are next generation therapeutics for cancer. However, there are still challenges which include selectively, side effects, and drug resistance. Nevertheless, with ongoing clinical development of these inhibitors and greater analysis of their target, CDK7 inhibitors will become a promising approach for treatment of cancer in the near future.The antioxidant properties of echinatin (Ech), isolated from liquorice, have recently been reported. It is well known that the free radical species can be deactivated by phenolic antioxidants via different mechanistic pathways. In this work, the scavenging of eighteen different reactive oxygen species (ROS) has been considered, focussing on three main working mechanisms, namely hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET). The investigations have been performed in different dielectric media, viz. gas phase, benzene, methanol and aqueous solution, using density functional theory (DFT) calculations at the M05-2X/6-311++G** level. Various molecular descriptors have been elucidated for Ech as well as the ROS and compared with the reference antioxidant molecule, trolox. In addition, the redox potentials and the equilibrium constants have been calculated to discuss the feasibility of the overall scavenging process. The results demonstrate that the 4-OH group is the first site for H-atom donation, followed by 4′-OH. Further, it has been found that HAT would be the most favourable mechanism in the gas phase. The SPLET mechanism is thermodynamically favoured in polar media like water and methanol, while in the case of non-polar solvents like benzene, the two mechanisms are observed to be competitive.Introduction Researchers have investigated the potential role of intestinal permeability in Crohn’s disease pathogenesis. Intestinal permeability is usually mediated by cytoskeleton and intercellular junctions. The myosin light chain kinase (MLCK) is an enzyme that activates the myosin light chain to exert its function related to cytoskeleton contraction and tight junction regulation. The correlation between MLCK and Crohn’s disease pathogenesis has been consistently proven. Areas covered This study aims to expand the understanding of the regulation and function of MLCK in Crohn’s disease. An extensive literature search in the MEDLINE database (via PubMed) has been performed up to Oct. 2020. The roles of MLCK in tight junction activation, intestinal permeability enhancement, and cell signal regulation are comprehensively discussed. Expert opinion Targeting the MLCK-related pathways such as TNF-α in CD treatment has been put into clinical use. More accurate targeting such as MLCK and TNFR2 has been proposed to reduce side effects. MLCK may also have the potential to become biomarkers in fields like CD activity. With the application of cutting age research methods and tools, the MLCK research could be accelerated.Background and purpose – It is unclear what degree of malalignment of a fracture of the distal radius benefits from reduction. This study addressed the following questions (1) What is the interobserver reliability of surgeons concerning the recommendation for a reduction for dorsally displaced distal radius fractures? (2) Do expert-based criteria for reduction improve reliability or not? Methods – We sent out 2 surveys to a group of international hand and fracture surgeons. On the first survey, 80 surgeons viewed radiographs of 95 dorsally displaced (0° to 25°) fractures of the distal radius. The second survey randomized 68 participants to either receive or not receive expert-based criteria for when to reduce a fracture and then viewed 20 radiographs of fractures with dorsal angulation between 5° and 15°. All participants needed to indicate whether they would advise a reduction or not. Results – In the 1st study, the interrater reliability of advising a reduction was fair (kappa 0.31). Multivariable linear regression analyses indicated that each additional degree of dorsal angulation increased the chance of recommending a reduction by 3%. In the 2nd study, reading criteria for reduction did not increase interobserver reliability for recommending a reduction. Interpretation – There is notable variation in recommendations for reduction that is not accounted for by surgeon or patient factors and is not diminished by exposure to expert criteria. Surgeons should be aware of their biases and develop strategies to inform patients and share the decision regarding whether to reduce a fracture of the distal radius.

Placenta praevia affects about 0.5% of pregnancies and due to constant increase in operative deliveries may become an important, clinical challenge throughout the next decades. Location of the placental plate within lower uterine segment is associated with increased risk of adverse perinatal outcomes. There were several reports pointing increased risk of small-for-gestational-age (SGA)/fetal growth restriction (FGR) in patients affected with abnormal location of the placenta. On the other hand, some studies ended up with opposite conclusions.

Due to ambiguous results we have undertaken a case-control study to investigate intrauterine growth among this group. We ran a pilot study to precisely define maternal, obstetrical and neonatal characteristics in order to avoid cofounders. Our study incorporated 56 patients in singleton pregnancies affected with placenta praevia and 124 patients in the control group (between 35 and 37 weeks of gestation).

Nonetheless, there were no statistical differences in the birthweight between the study and control group (2882.5 g vs. 2805 g, p = ns). Moreover, rates of the newborns with birthweight corresponding <10th percentile and >90th did not differ significantly. Even further analysis that included parity did not reveal any differences between both groups.

Placenta praevia does not affect the intrauterine growth and shall not be considered as a risk factor for SGA/FGR. In patients affected with abnormal location of the placenta additional scans for fetal well-being assessment are not indicated.

Placenta praevia does not affect the intrauterine growth and shall not be considered as a risk factor for SGA/FGR. In patients affected with abnormal location of the placenta additional scans for fetal well-being assessment are not indicated.Introduction Hallucinations in Parkinson’s disease are common, can complicate medication management and significantly impact upon the quality of life of patients and their carers. Areas covered This review aims to examine current evidence for the management of hallucinations in Parkinson’s disease. Expert opinion Treatment of hallucinations in Parkinson’s disease should be both individualized and multifaceted. Screening, education, medication review and the avoidance of common triggers are important. For well-formed visual hallucinations, acetylcholinesterase inhibitors are recommended first-line. Refractory or severe symptoms may require the cautious use of atypical antipsychotics. Antidepressants may be beneficial in the appropriate setting. Unfortunately, current therapies for hallucinations offer only limited benefits and future research efforts are desperately required to improve the management of these challenging symptoms.Conventional formulations cannot sufficiently control seizures and influence on cognitive corruption and oxidative stress with chronic usage in patients with epilepsy. To defeat this issue, it was planned to develop polymeric liposome formulations that are using for their bioavailability and enhancer impact in oral epilepsy treatment. In this study, chitosan-coated liposomal formulations that encapsulate carbamazepine (CBZ) and coenzyme Q10 (CoQ10) were prepared and optimized by utilizing response surface methodology (RSM). Encapsulation efficiencies of CBZ and CoQ10, which were chosen as dependent variables for optimized chitosan-coated liposomal formulations were determined as 76.13%±2.34% and 82.36%±3.15%, respectively. Narrow size distribution was provided with an average size of 187.1 ± 2.35 nm, while a spherical and uniform shape was approved with transmission electron microscopy analyses. Cumulative release of 78.23% for CBZ and 27.12% for CoQ10 was obtained after 24 hours of in-vitro release study in sink conditions. Physical stability analyses demonstrated that optimum liposomes were convenient for storage at 5 ± 3 °C for at least 90 days. As a result, optimum chitosan-coated liposome containing CBZ and CoQ10 formulations could be suggested as a hopeful approach concerning their release, particle size, high encapsulation efficiency and stability for the treatment of epilepsy.Oral delivery of peptide and proteins is challenging due to their poor physical and chemical stability which usually results in inadequate therapeutic efficacy. Nanoparticles encapsulating insulin was developed by the ionic gelation technique using sulfobutyl ether-β-cyclodextrin as an anionic linker. Phospholipid hybrid nanoparticles were formulated by utilizing ionic gelation and thin-film hydration methods using D-α-Tocopheryl polyethylene glycol 1000 succinate, sodium deoxycholate separately and in combination to take the advantage of liposomes and nanoparticles also various absorption enhancement mechanisms. All formulations were characterized and tested for in vitro gastrointestinal stability, in vitro drug release, and cytotoxicity. On the other hand, in vivo effects of developed formulations on reducing blood glucose levels were monitored for 8 hours. Phospholipid hybrid nanoparticles including D-α-Tocopheryl polyethylene glycol 1000 succinate and sodium deoxycholate in combination with 548.7 nm particle size, 0.332 polydispersity index, 22.0 mV zeta potential, and 61.9% encapsulation efficiency, exhibited desired gastrointestinal stability and insulin release in vitro. In addition, the formulation proved its safety with cytotoxicity studies on L929 cells. The subjected phospholipid hybrid nanoparticle formulation was found to be the most effective formulation by reducing and maintaining blood glucose levels with avoiding fluctuations.Introduction COVID-19 outbreak has infected 34.20 million people with 1019 thousand deaths in more than 125 countries till 30 September 2020. Due to the unavailability of vaccine or targeted novel drug therapy against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), screening of existential medical treatments facilitates identification of promising drugs for the treatment and management of COVID-19. Areas covered The review article highlights repurposing of antiviral, antimalarial, antineoplastic, antidiabetic, analgesic, and immunomodulatory drugs. Furthermore, clinical trials, in-vitro studies, benefits, adverse effects, toxicities, mechanisms of action, and regulatory status of drugs are covered in this article. Expert opinion Lack of conclusive results from randomized clinical trials indicates absence of specific drugs for treatment of COVID-19. Unavailability of complete data regarding safety, efficacy, and adverse reactions of drugs restricts the recommendation of clinical advice on dose and duration of the drug therapy. Remdesivir and favipiravir show promising outcomes but more clinical evidence is required for use in large populations. Experimental and repurposed drug therapies targeting spike and envelope proteins, Mpro, 3CLpro and PLpro enzymes, and RdRp and TMPRSS2 genes show capability to produce effective anti-SARS-CoV-2 action. Development of vaccine against SARS-CoV-2 will offer long-term solution to terminate spread of this global pandemic.

Colorectal surgery has markedly advanced due to the introduction of laparoscopic and robotic surgery. During the past 20years, these two modalities have been further enhanced by fluorescence imaging.

This article will review the common and novel uses for fluorophores in colorectal surgery, including tissue perfusion for anastomotic creation, ureter identification, lymphatic mapping, and tumor localization.

The versatility of this technology permeates through many aspects of colorectal procedures. The white light spectrum has historically been the only available modality to visualize tissue perfusion, tumor implants, and structures including the ureters and lymph nodes. The ability of the near-infrared spectrum to penetrate biologic tissues allows the identification of these structures with injection of fluorophores. The two most common intravenously utilized fluorophores are methylene blue and indocyanine green. Additionally, novel tumor marker-specific fluorophores are being investigated for purposes of cancer detection.

The versatility of this technology permeates through many aspects of colorectal procedures. The white light spectrum has historically been the only available modality to visualize tissue perfusion, tumor implants, and structures including the ureters and lymph nodes. The ability of the near-infrared spectrum to penetrate biologic tissues allows the identification of these structures with injection of fluorophores. The two most common intravenously utilized fluorophores are methylene blue and indocyanine green. Additionally, novel tumor marker-specific fluorophores are being investigated for purposes of cancer detection.

The objective of this study was to quantify the association between duration of labor induction in nulliparous women with hypertensive disorders of pregnancy and maternal and neonatal morbidity.

This was a secondary analysis of a multicenter cohort study of 228,438 deliveries in 19 U.S. hospitals. The analysis included nulliparous women ≥18 years old with singleton gestation diagnosed with hypertensive disorders of pregnancy and undergoing induction of labor for that indication. Duration of labor induction, defined as time from admission to delivery, was examined by 4 h intervals from <12 h to ≥24 h in relation to maternal and neonatal composite outcomes. Maternal composite outcome included operative vaginal delivery, chorioamnionitis, blood transfusion, intensive care unit admission, placental abruption, 3rd or 4th degree perineal laceration, endometritis, postpartum hemorrhage, or venous thromboembolism. Neonatal composite outcome included neonatal intensive care unit (NICU) admission, respiratory di.001). After multivariable adjustment, duration of labor induction was associated with increased risks of maternal composite outcome after 24 h (aRR 1.39, 95% CI 1.20-1.62) and neonatal composite outcome after 24 h (aRR 1.32, 95% CI 1.11-1.56).

In nulliparous women with hypertensive disorders of pregnancy, duration of labor induction was associated with increased risks for maternal and neonatal morbidity after 24 h.

In nulliparous women with hypertensive disorders of pregnancy, duration of labor induction was associated with increased risks for maternal and neonatal morbidity after 24 h.Polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) have been extensively studied for their use in film formation. Poloxamer 407 (P407) is a block copolymer that has thermo-responsive and surfactant properties when used in pharmaceutical systems. These polymers are already used in liquid or semi-solid systems for ocular and parenteral drug delivery. However, the effect of P407 presence in solid pharmaceutical films composed of different PVAPVP ratios have not been investigated yet. Therefore, this work investigated the influence of P407 added to the binary polymer mixture of PVA and PVP for the development of solid films aiming for pharmaceutical applications. The rheological properties of dispersions were investigated, and films were prepared by solvent casting method using different P407PVAPVP ratios according to a factorial design 23 (plus center point). The mechanical and in vitro mucoadhesive properties of films, as well as the disintegration time were investigated. Systems presented high mechanical resistance, mucoadhesion, and disintegration timeless than 180 s. It was found that higher concentrations of PVA increase mechanical properties and decrease disintegration time, and higher proportions of PVP and P407 increased mucoadhesion. The films could be classified as fast disintegrating films and represent a promising alternative for modifying drug delivery and pharmaceutical applications.

Cardiac troponins are important markers for diagnosis of acute myocardial infarction (AMI) in general population; however, chronically-elevated troponins levels are often seen in patients with renal insufficiency, which reduce their diagnostic accuracy. The aim of our study was to access the diagnostic values of initial high-sensitive cardiac troponin T (hs-cTnT) and relative change of hs-cTnT for AMI in patients with and without renal insufficiency.

Cardiac care unit patients with elevated hs-cTnT levels in 2017-2018 were enrolled. Receiver operating characteristic (ROC) curves were used to evaluate initial hs-cTnT levels and relative changes after 3 h of enrollment for diagnosis of AMI in patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m

(low), and eGFR ≥ 60 mL/min/1.73 m

(normal).

Of 359 patients, 240 patients had low eGFR, and 119 patients had normal eGFR. The area under the ROC curve (AUC) for the initial hs-cTnT levels was 0.58 (95% CI, 0.5-0.65,

 = 0.053) among patients with low eGFR and 0.54 (95% CI, 0.4-0.67,

 = 0.612) among patients with normal eGFR. AUCs for relative changes of hs-cTnT were 0.82 (95% CI, 0.76-0.88,

 < 0.001) in patients with low eGFR and 0.82 (95% CI, 0.71-0.91,

 < 0.001) in patients with normal eGFR. Optimal cutoff values for the relative changes in hs-cTnT were 16% and 12% in patients with low eGFR and normal eGFR, respectively.

Relative changes in hs-cTnT levels had better diagnostic accuracy than initial hs-cTnT levels.

Relative changes in hs-cTnT levels had better diagnostic accuracy than initial hs-cTnT levels.

Limited early results indicate that the COVID-19 outbreak has had a significant impact on the mental health of children and adolescents. Pediatric emergency departments (PED) play a pivotal role in the identification, treatment, and coordination of care for children with mental health disorders, however, there is a dearth of literature evaluating the effects of the COVID-19 pandemic on mental health care provision in the PED.

We sought to evaluate whether changes in frequency or patient demographics among children and adolescents presenting to the PED has occurred.

This is a cross-sectional study conducted at the Yale New Haven Children’s Hospital (YNHCH) PED. Data representing the early COVID-19 pandemic period was abstracted from the electronic medical record and compared using descriptive statistics to the same time period the year prior. Patient demographics including patient gender, ED disposition, mode of arrival, race-ethnicity, and insurance status were assessed.

During the pandemic period, 148 patients presented to the YNHCH PED with mental health-related diagnoses, compared to 378 in the pre-pandemic period, a reduction of 60.84%. Compared to white children, black children were 0.55 less likely to present with a mental health condition as compared to the pre-pandemic study period (

= 0.002; 95% CI 0.36-0.85).

Children with mental and behavioral health disorders who seek care in PEDs may be at risk for delayed presentations of mental health disorders. African American children may be a particularly vulnerable population to screen for mental health disorders as reopening procedures are initiated and warrants further study.

Children with mental and behavioral health disorders who seek care in PEDs may be at risk for delayed presentations of mental health disorders. African American children may be a particularly vulnerable population to screen for mental health disorders as reopening procedures are initiated and warrants further study.The extent to which students’ level of depressive and anxiety symptoms and student engagement were predicted by parental emotional support, monitoring and harsh parenting was investigated using a series of multiple regression analyses. Grade six students from public primary schools (n = 293; 49% females, 51% males; mean age = 10 years) in Barbados completed the Revised Children’s Anxiety and Depression Scale, a Parenting Questionnaire and an adapted Student Engagement scale. Students’ level of depressive symptoms were predicted by parental emotional support and harsh parenting, but not by parental monitoring. With the exception of harsh parenting, neither parental emotional support nor parental monitoring were significant predictors of the anxiety levels of students. Student engagement was predicted by all three types of parenting practices. Limitations, recommendations for future research and practical implications of the study are discussed.

Massive fetomaternal hemorrhage (FMH) is a rare but sometimes life-threatening event, and surviving neonates may suffer major neurological complications. Severe neonatal anemia (SNA) affected by massive FMH is less reported in the literature. This study aims to explore the clinical characteristics, laboratory diagnoses, treatments and outcomes of SNA affected by massive FMH.

Data were collected retrospectively from the hospital’s electronic medical record system. All neonates born in the hospital and admitted to the neonatal unit diagnosed as SNA affected by massive FMH from 1 January 2013 to 31 June 2017 were included.

A total of 8 cases of SNA affected by FMH were identified among 6825 neonates admitted to the neonatal unit. They all presented with pallor but without hydrops at birth. Median gestational age and birthweight were 37

(36

‒40

) weeks and 2,625 (2300‒3050) g, respectively. Median hemoglobin level was 39.5 (25‒53) g/L at birth and 109.5 (94-127) g/L at discharge. Median maternal serumge. Surviving neonates of massive FMH might have a good outcome despite severe anemia at birth.

This study strengthens the idea that maternal AFP testing is valuable to confirm massive fetomaternal hemorrhage. Surviving neonates of massive FMH might have a good outcome despite severe anemia at birth.CerSs (ceramide synthases), a group of enzymes that catalyze the formation of ceramides from sphingoid base and acyl-CoA substrates. As far, six types of CerSs (CerS1-CerS6) have been found in mammals. Each of these enzymes have unique characteristics, but maybe more noteworthy is the ability of individual CerS isoform to produce a ceramide with a characteristic acyl chain distribution. As key regulators of sphingolipid metabolism, CerSs highlight their unique characteristics and have emerging roles in regulating programmed cell death, cancer and many other aspects of biology. However, the role of CerSs in lung cancer has not been fully elucidated. In this study, there was no significant change in the sequence or copy number of CerSs gene, which could explain the stability of malignant tumor development through COSMIC database. In addition, gene expression in lung cancer was examined using the OncomineTM database, and the prognostic value of each gene in non-small cell lung cancer (NSCLC) was analyzed by Kaplan-Meier analysis. The results showed that high mRNA expression levels of CerS2, CerS3, CerS4 and CerS5 in all NSCLC patients were associated with improved prognosis. Among them, CerS2 and CerS5 are also highly expressed in adenocarcinoma (Ade), but not in squamous cell carcinoma (SCC). In contrast, high or low expression of CerS1 and CerS6 no difference was observed in patients with NSCLC, Ade and SCC. Integrated the data of this study suggested that these CerSs may be a potential tumor markers or drug target of new research direction.

Self-inflicted enucleation, also known as auto-enucleation (AE) or Oedipism, is an uncommon and severe form of ocular injury which presents as an ophthalmic and psychiatric emergency. Usually known to occur with untreated psychosis, this case is a rare report which demonstrates AE as a result of a subsequently diagnosed drug induced psychosis. We report the clinical presentation, management and for the first time a detailed speculative account about the mechanism of AE, based on our clinicopathologic findings.

A 53-year old Afro-Caribbean patient was arrested following an altercation and was incarcerated awaiting arraignment. The patient had no previous psychiatric history but tested positive for cannabis, opiates and cocaine as well as admitting to illicit drug use in the community. Whilst in custody, the patient self-enucleated his right eye. The patient declined consent to eye examination and was subsequently admitted under section 2 of the Mental Health Act. After full work-up including Goldmann visuaanagement strategies and complications of AE.A rich of 3,4-seco-lupane triterpenoids (3,4-SLT), including chiisanoside (CSS), divaroside (DVS), sessiloside-A1 (SSA), chiisanogenin (CSG), sessiligenin (SSG), were isolated from the ethanol extract of the leaves of Eleutherococcus sessiliflorus (LES). The present study was performed to explore the cytotoxic and anti-tumor effects of the isolated five ones, as well as potential molecular mechanisms. The results of a CCK-8 assay demonstrated that these 3,4-SLT can inhibit the growth of HepG2 cells, and SSG showed the most significant cytotoxicity. Hoechst 33258 fluorescence staining and Annexin V-FITC/PI staining indicated that 3,4-SLT in LES can induce HepG2 cell apoptosis effectively. The AutoDock Vina program was used to simulate molecular docking of drugs and targets to discuss possible pharmacological mechanisms. Besides, western blot and qRT-PCR results indicated that SSG can inhibit PI3K/AKT signaling pathway through controlling multi-targets. This study suggested that 3,4-SLT might become a new research hotspot for antineoplastic drugs.

To illustrate the effect of corticosteroids and heparin, respectively, on coronavirus disease 2019 (COVID-19) patients’ CD8+ T cells and D-dimer.

In this retrospective cohort study involving 866 participants diagnosed with COVID-19, patients were grouped by severity. Generalized additive models were established to explore the time-course association of representative parameters of coagulation, inflammation and immunity. Segmented regression was performed to examine the influence of corticosteroids and heparin upon CD8+ T cell and D-dimer, respectively.

There were 541 moderate, 169 severe and 156 critically ill patients involved in the study. Synchronous changes of levels of NLR, D-dimer and CD8+ T cell in critically ill patients were observed. Administration of methylprednisolone before 14 DFS compared with those after 14 DFS (

 = 0.154%, 95% CI=(0, 0.302),

=.048) or a dose lower than 40 mg per day compared with those equals to 40 mg per day (

 = 0.163%, 95% CI=(0.027, 0.295),

=.020) significantly increased the rising rate of CD8+ T cell in 14-56 DFS.

The parameters of coagulation, inflammation and immunity were longitudinally correlated, and an early low-dose corticosteroid treatment accelerated the regaining of CD8+ T cell to help battle against SARS-Cov-2 in critical cases of COVID-19.

The parameters of coagulation, inflammation and immunity were longitudinally correlated, and an early low-dose corticosteroid treatment accelerated the regaining of CD8+ T cell to help battle against SARS-Cov-2 in critical cases of COVID-19.This online survey took place on March 7, 2020 at the beginning of the COVID-19 outbreak in the United States. Participants (n = 698) completed an online survey in which they were asked to reflect on their mediated and interpersonal information consumption, in addition to reporting on risk perceptions, general efficacy perceptions, and preventative behaviors specific to COVID-19 in the past seven days. Participant age and chronic condition status were controlled for in all analyses. Time spent consuming news, social media, and health website information was not related to risk perceptions. Time spent on health websites predicted time spent having interpersonal conversations about COVID-19, as well as general efficacy levels. Following the Extended Parallel Process Model, perceived severity, perceived susceptibility, and general perceived efficacy predicted preventative behaviors. The vast majority of participants did report taking preventative action against COVID-19, most commonly in the form of hand washing, with many enacting stronger preventative behaviors that had yet to be recommended for the general population. Overall, mediated and interpersonal information exposure had minimal effects on perceived risk and perceived general efficacy, which in turn predicted 27.5% of the variance in preventative behavior. Efficacy was the most powerful among these predictors, and health websites, specifically governmental websites, appeared to be underutilized resources with the potential to promote efficacy during outbreaks. Further research is needed to understand causation in these relationships and to assist in successful message transmission.

The superiority of primary arthrodesis (PA) versus open reduction and internal fixation (ORIF) in Lisfranc injuries has been debated. Meta-analyses comparing these surgical options have reached contradicting conclusions. The goal of this article is to determine why different conclusions were reached and provide clarity on the comparable outcomes of PA and ORIF in Lisfranc injuries.

A systematic literature review was conducted by searching for „meta-analysis” AND „Lisfranc” with keywords such as „ORIF” OR „open reduction” OR „arthrodesis” OR „fusion.” Five meta-analysis articles discussing PA and ORIF in Lisfranc injuries were identified. Study outcomes were extracted from each article, and contradicting conclusions were identified for analysis.

PA had lower rates of hardware removal. There was no difference between PA and ORIF when considering revision surgery, anatomic reduction, postoperative infection, total complications, and patient satisfaction. However, contradicting conclusions were reached for return to duty, the American Orthopaedic Foot and Ankle Society (AOFAS) score, and visual analogue scale (VAS) score. Conclusions. There was no difference in PA and ORIF for return to work and VAS score. Repeat meta-analysis with truly equivocal outcomes would be necessary to reach a valid conclusion for return to full activity and AOFAS midfoot scores.

Level II Therapeutic studies.

Level II Therapeutic studies.Despite the considerable growth of interest in medical tourism in the last decade, there is no standard procedure to measure the pivotal factors in medical tourism destinations. Medical tourism is a rising global phenomenon that is strongly dependent on innovation and knowledge management. Being both innovative and systematic in medical tourism requires thought enrichment in knowledge management in hospitals. By applying a quantitative method, „knowledge management-oriented innovation” items have been used in this study to analyze new products or services related to active hospitals in medical tourism in Iran. This study presents the positive effects of the most essential knowledge management areas such as time, cost, and quality management orientation, on operational performance through the mediating role of innovation speed. In the current study, hospitals of Iran that are active in the medical tourism area have been considered as the final destination. Additionaly, because this study coincides with the coronavirus COVID-19 pandemic as the global health crisis which has a considerable effect on medical tourism, the managerial implications have been developed to help managers and decision-makers in order to apply the obtained findings during the pandemic and post-pandemic period.

The study aimed to compare eye outcomes between the standard and accelerated corneal cross-linking (CXL) protocols over a 1-year follow-up, and assess whether the accelerated protocols are non-inferior to the standard.

A retrospective cohort study including patients older than 18 years diagnosed with progressive keratoconus who underwent a CXL procedure. The primary outcome was defined as an increase of more than 1.5 diopter (D) in Kmax. The analysis included intra- and inter-group comparisons assessing differences in eye characteristics before and 12 months after the procedure. Furthermore, we assessed whether the accelerated procedures were non-inferior to the standard regarding Kmax change after 12 months.

Eighty-four patients included in the study of which 23, 37 and 23 underwent the standard CXL (group I), 10-min. (group II) and the 3-min. (group III) accelerated procedures, respectively. Intra-group comparison before and after 12 months of mean Ksteep and anterior corneal astigmatism showed significant improvement only for group I (-0.3D decrease for both). Inter-group comparison showed better results after 12 months for group I (-0.9 ± 1.2) compared to group III (0.1 ± 0.8) in Ksteep, Kmean (-0.5+1. vs 0.1+0.7, respectively) and anterior astigmatism (-0.5 + 0.9 vs 0.3+1.1, respectively). We could not declare that the accelerated CXLs are non-inferior to the standard (

-value = 0.11 and 0.15).

The standard CXL showed better results for keratometry and astigmatism in comparison with the accelerated. Therefore, the wide use of the accelerated CXL should be considered and reviewed for longer follow-up time and larger sample size in focus on the visual acuity parameters.

The standard CXL showed better results for keratometry and astigmatism in comparison with the accelerated. Therefore, the wide use of the accelerated CXL should be considered and reviewed for longer follow-up time and larger sample size in focus on the visual acuity parameters.The chemical profile and phytotoxic activity of the essential oil extracted from Artemisia sieversiana was investigated. In total 17 compounds were identified by GC/MS, representing 99.17% of the entire oil, among which α-thujone (64.46%) and eucalyptol (10.15%) were the most abundant constituents. The major components, their mixture as well as the essential oil exhibited significant phytotoxic activity against Amaranthus retroflexus, Medicago sativa, Poa annua and Pennisetum alopecuroides, with their IC50 values ranged from 1.55 ∼ 6.21 mg/mL (α-thujone), 1.42 ∼ 17.81 mg/mL (eucalyptol), 0.23 ∼ 1.05 mg/mL (the mixture), and 1.89 ∼ 4.69 mg/mL (the essential oil) on the four tested species. The mixture of the major constituents exerted more potent effect compared with each individual compound, indicating the possible involvement of synergistic effect of these two compounds.This paper presents an in-depth chemical and analytical study of a natural substance extracted from Ammodaucus leucotrichus Coss. & Dur and its derivatives after hemisynthesis. The analysis was performed using Diffusion-Ordered Spectroscopy (NMR DOSY) and Differential Scanning Calorimetry (DSC) as general methods. The results show an interesting chemical reactivity towards coumarin-derived bisnucleophiles (4-hydroxycoumarin and triacetic acid lactone), and products obtained by hemisynthesis of pyrano[4,3-b]pyrane derivatives following Knoevenagel condensation and Michael’s addition on this natural substance with the use of 4-pyrolidinopyridine organobase as catalyst.

Ocular adnexal lymphomas (OAL) constitute 55% of all orbital tumors. Waldenström Macroglobulinemia (WM) presenting as an orbital mass with diffuse extraocular muscle (EOM) involvement is rare. We report an elderly patient who presented to the ophthalmologist for an orbital mass which on evaluation, turned out to an ocular adnexal WM.

A 75 years old man presented with a palpable mass in the left anterior superior orbit and bilateral restricted ocular motility in all gazes. Computed tomography scan revealed a hyperdense mass with diffuse thickening of extraocular muscles and enlarged lacrimal gland on the left side. Incisional biopsy of the mass revealed a lymphoproliferative neoplasm with plasmacytic morphology. Immunohistochemistry (IHC) of the orbital mass as well as the bone marrow was sought, lymphoplasmacytic lymphoma (CD20+, CD38+, MUM1+, BCL 2+, CD3-, CD5-, CD10-, CD23-, cyclin D1). Bone marrow flow cytometry showed CD5-, CD10- kappa restricted B cell neoplasm. Serum analysis significantly elevated IgM levels. This indicated a diagnosis of ocular adnexal Waldenström Macroglobulinemia.

This case highlights the importance of clinical evaluation, histopathology, and immunohistochemistry for phenotyping of ocular adnexal lymphomas.

This case highlights the importance of clinical evaluation, histopathology, and immunohistochemistry for phenotyping of ocular adnexal lymphomas.With an increasing aging population worldwide, loneliness among elderly individuals has become a salient societal problem. Fortunately, the last decade has also witnessed an upsurge in information and communication technology (ICT), which is ubiquitously deployed and integrated into our daily lives, including the lives of elderly people. This research investigates the potential exploitation of well-developed ICT to mitigate loneliness among the elderly. Specifically, we examined the effects of two dimensions of ICT use communication use and information use. Moreover, we examined the moderating effects of two relevant features in the elderly population, namely, ICT self-efficacy and health consciousness. We applied structural equation modeling (SEM) to evaluate survey data from mainland China comprising 436 effective responses from the elderly population. We find that ICT use has a positive effect on loneliness among the elderly, and our results support and deepen this understanding, indicating that ICT self-efficacy and health consciousness can moderate the relationship between ICT use and loneliness.