Syntheses,Cholinesterases Inhibition,and Molecular Docking Studies of Pyrido[2,3‐b]pyrazine Derivatives

Cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), have a role in cholinergic deficit which evidently leads to Alzheimer's disease (AD). Inhibition of cholinesterases with small molecules is an attractive strategy in AD therapy. This study demonstrates synthesis of pyrido[2,3‐b]pyrazines ( 6a ‐ 6q ) series, their inhibitory activities against both cholinesterases, AChE and BChE, and molecular docking studies. The bioactivities data of pyrido[2,3‐b]pyrazines showed 3‐(3′‐nitrophenyl)pyrido[2,3‐b]pyrazine 6n a potent dual inhibitor among the series against both AChE and BChE with IC₅₀ values of 0.466 ± 0.121 and 1.89 ± 0.05 μm , respectively. The analogues 3‐(3′‐methylphenyl)pyrido[2,3‐b]pyrazine 6c and 3‐(3′‐fluorophenyl)pyrido[2,3‐b]pyrazine 6f were found to be selective inhibition for BChE with IC₅₀ values of 0.583 ± 0.052 μm and AChE with IC₅₀ value of 0.899 ± 0.10 μm , respectively. Molecular docking studies of the active compounds suggested the putative binding modes with cholinesterases. The potent compounds among the series could potentially serves as good leads for the development of new cholinesterase inhibitors.     

The effects simultaneous inhibition of dipeptidyl peptidase-4 and P2X7 purinoceptors in an in vivo Parkinson’s disease model

Metabolic Brain Disease - Loss of dopaminergic neurons following Parkinson’s disease (PD) diminishes quality of life in patients. The present study was carried out to investigate the...     

Transesophageal Echocardiography of Intracardiac Thrombus in Congenital Heart Disease and Atrial Flutter: The Importance of Thorough Examination of the Fontan

Transesophageal echocardiography (TEE) is used in atrial flutter or fibrillation (AFF) before electric cardioversion to detect intracardiac thrombi. Previous studies have described the use of TEE to diagnose intracardiac thrombi in the left atrium and left atrial appendage, which has an incidence of 8 % among patients without congenital heart disease (CHD). In their practice the authors have noted a significant incidence of intracardiac thrombi in other structures of patients with CHD and AFF. This study aimed to determine the incidence and location of intracardiac thrombi using TEE in patients with CHD requiring electric cardioversion of AFF and to compare the use of TEE and transthoracic echo (TTE) to detect intracardiac thrombus in this population. A retrospective chart review of TEE and TTE findings for all patients with CHD who had electric cardioversion of AFF at our institution from 2005 to 2013 was conducted. The diagnosis, presence, and location of intracardiac thrombus were determined. The TEE and TTE results were compared. The study identified 27 patients with CHD who met the study entry criteria at our institution between 2005 and 2013. Seven of these patients had a single ventricle with Fontan palliation. All the patients presented with AFF and had TEE before electric cardioversion. No patients were excluded from the study. The patients ranged in age from 2 to 72 years (median, 21 years) and weighed 17–100 kg (median, 65 kg). The duration of AFF before TEE and attempted cardioversion ranged from 1 day to 3 weeks (median, 3.5 days). Intracardiac thrombus was present in 18 % (5/27) of the patients and in 57 % (4/7) of the Fontan patients with AFF. No embolic events were reported acutely or during a 6-month follow-up period. Among patients with CHD who present with AFF, a particularly high incidence of intracardiac thrombi is present in the Fontan patients that may be difficult to detect by TTE. Thorough TEE examination of the Fontan and related structures is indicated before electric cardioversion of AFF. The incidence of intracardiac thrombus in CHD patients is more than double that reported in non-CHD patients.     

Relationship between Pancreas Exocrine Insufficiency and Cardiac Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus

BackgroundThe exocrine function of the pancreas is controlled by the autonomic nervous system (ANS), and autonomic neuropathy is a common and serious complication of diabetes. There are many factors contributing to the development of autonomic neuropathy in diabetic patients. Cardiovascular tests have been developed to evaluate the function of the ANS. This study investigated the relationship between cardiovascular autonomic neuropathy (CAN) and pancreas exocrine insufficiency (PEI) in diabetic patients.Methods This study evaluated 110 individuals with type 2 diabetes mellitus (T2DM) and 40 healthy volunteers. Autonomous neuropathy tests were utilized to diagnose patients, and Ewing and Clarke’s criteria were employed to assess the severity of autonomous dysfunction. Stool samples were also collected from patients to measure fecal elastase-1 (FE-1). Results A 65.5% incidence of PEI was observed in DM patients. There was no significant correlation among the duration of disease, C-peptide, HbA1c, and PEI, respectively (P = .782, P = .521, P = .580). However, a significant difference between DM patients and controls in terms of cardiac dysautonomia (P = .001) was seen. Moreover, a statistically significant correlation between the degree of cardiac dysautonomia and FE-1 level was observed within the patient group (P =.001).Conclusion It is possible that the disruption of exocrine hormone secretion in the pancreas due to the impairment of enteropancreatic reflexes is secondary to diabetic autonomic neuropathy and resulting in PEI. This study also showed that autonomic neuropathy might develop and cause PEI in diabetic patients without known added confounding factors.     

Testing the effects on information use by older versus younger women of modality and narration style in a hospital report card

BackgroundHospital report cards (HRCs) are usually presented in a textual and factual format, likely hampering information processing.ObjectiveThis study aimed to investigate the effects of audiovisual and narrative information in HRCs on user responses, and to test differences between older and younger women.DesignA 2 (modality [textual vs. audiovisual]) × 3 (narration style [factual vs. process narrative vs. experience narrative]) online experiment was conducted. Information about breast cancer care was used as a case example. Age (younger [<65] vs. older [≥65]) was included as a potential effect modifier.Setting and ParticipantsA total of 631 disease‐naïve women (M _age = 56.06) completed an online survey. The outcomes were perceived cognitive load, satisfaction, comprehension, information recall and decisional conflict. Data were analysed using AN(C)OVAs.ResultsAudiovisual (vs. textual) information resulted in higher information satisfaction across age groups, but was associated with lower comprehension in older women. An experience narrative (vs. factual information) increased satisfaction with attractiveness and emotional support of the information only in older women. A three‐way interaction effect was found, suggesting that older women were most satisfied with the comprehensibility of audiovisual factual or textual process narrative information. Younger women were most satisfied with the comprehensibility of audiovisual process narrative or textual factual information.Discussion and ConclusionAudiovisual and narrative information in an HRC showed beneficial effects on satisfaction measures. In particular, audiovisual information could be incorporated into HRCs to increase satisfaction with information.Public ContributionLay persons helped in optimizing the visuals used in the stimulus materials by checking for clarity.     

Development of Therapeutic and Prophylactic Zinc Compositions for Use against COVID-19: A Glimpse of the Trends,Inventions, and Patents

Zinc is an essential nutrient for human health; it is involved in the catalytic, structural, and regulatory functions of the human cellular system. Different compositions of zinc, as well as its pharmaceutically acceptable salts, are available on the market. Recent studies have demonstrated the role of zinc in combating COVID-19. It has been determined that zinc prevents the entry of SARS-CoV-2 into cells by lowering the expression of ACE-2 receptors and inhibiting the RNA-dependent RNA polymerase of SARS-CoV-2. Zinc also prevents the cytokine storm that takes place after the entry of SARS-CoV-2 into the cell, via its anti-inflammatory activity. The authors believe that no study has yet been published that has reviewed the trends, inventions, and patent literature of zinc compositions to treat/prevent COVID-19. Accordingly, this review has been written in order to fill this gap in the literature. The information about the clinical studies and the published patents/patent applications was retrieved from different databases. This review covers patent literature on zinc compositions up to 31 January 2022. Many important patents/patent applications for zinc-based compositions filed by innovative universities and industries were identified. The patent literature revealed zinc compositions in combination with zinc ionophores, antioxidants, antivirals, antibiotics, hydroxychloroquine, heparin, ivermectin, and copper. Most of these studies were supported by clinical trials. The patent literature supports the potential of zinc and its pharmaceutical compositions as possible treatments for COVID-19. The authors believe that countless zinc-based compositions are still unexplored, and there is an immense opportunity to evaluate a considerable number of the zinc-based compositions for use against COVID-19.     

RCT of a Manualized Social Treatment for High-Functioning Autism Spectrum Disorders

This RCT examined the efficacy of a manualized social intervention for children with HFASDs. Participants were randomly assigned to treatment or wait-list conditions. Treatment included instruction and therapeutic activities targeting social skills, face-emotion recognition, interest expansion, and interpretation of non-literal language. A response-cost program was applied to reduce problem behaviors and foster skills acquisition. Significant treatment effects were found for five of seven primary outcome measures (parent ratings and direct child measures). Secondary measures based on staff ratings (treatment group only) corroborated gains reported by parents. High levels of parent, child and staff satisfaction were reported, along with high levels of treatment fidelity. Standardized effect size estimates were primarily in the medium and large ranges and favored the treatment group.     

Discussions on Implantable Cardioverter-Defibrillator Deactivation in Patients Receiving Radiation Therapy: A Missed Opportunity

Established guidelines discuss end-of-life care in patients with implantable cardioverter-defibrillators (ICDs). It is not known how frequently these discussions take place in patients who have ICDs and are receiving active treatment for cancer. Chart review from a large regional cardiac and cancer center from 2005 to 2019 highlighted that discussions on ICD deactivation were infrequent (28% of patients). Receipt of a palliative care consultation increased the likelihood of patients having discussions on ICD deactivation during this time. Collaboration with palliative care teams may facilitate discussions on ICD deactivation during this opportune time.