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New pyrazole derivatives 2–5 were synthesized and evaluated for their COX-1 and COX-2 inhibitory activity in vitro. All compounds showed good inhibitory activity at a nanomolar level and most compounds exhibited selectivity towards COX-2 inhibition. Compounds 2a, 3b, 4a, 5b and 5e exhibited IC 50 towards COX-2 enzyme of 19.87, 39.43, 61.24, 38.73 and 39.14 nM, respectively. Furthermore, compounds 3b, 4a, 5b and 5e exhibited a selectivity index of 22.21, 14.35, 17.47 and 13.10, respectively. The most active compounds were further subjected to in vivo anti-inflammatory assay. The tested compounds showed better or comparable activity to celecoxib as positive control. In order to explore their binding mode and selectivity behaviour, molecular docking in the active site of COX-2 was carried out for these derivatives. Analysis of the docked poses of the compounds showed that they adopt similar conformations to the highly selective COX-2 inhibitor, SC-558. The docking pose of compound 3b was confirmed by molecular dynamics. All the tested compounds exhibited potent inhibitory effect on the production of PGE 2 , in addition to their inhibition of COX-2 enzyme. Image 1 • Novel pyrazole derivatives bearing benzenesulfonamide. • In vitro COX-1 and COX-2 inhibition assay. • In vitro PGE 2 determination and mPGES1 expression. • In vivo anti-inflammatory assay. • Molecular docking study on the active site of COX-1 and COX-2. [ABSTRACT FROM AUTHOR]

Isoquinoline and its derivatives, which constitute an important category of heterocyclic compounds and are found in a variety of naturally occurring alkaloids, serve a variety of biological purposes such as a potent agonist for human melatonin receptors 1. This research was conducted in an attempt to develop new dihydroisoquinoline molecules (III and IV). Single-crystal X-ray crystallography study validated their structures. The Hirshfeld surface analysis identifies intermolecular interactions by using a 2-D fingerprint map to recognize each type's relative contribution H⋅⋅⋅H connections are discovered to be dominating. The interaction energies between chemical pairs in crystal structures were found using an energy framework analysis. The DFT investigation demonstrates the electronic stability and reactivity of the compounds using the HOMO-LUMO and global reactivity descriptors, indicating that IV has higher chemical reactivity than III. The derived polarizability (αo) and hyperpolarizability (βo) values were used to calculate the optical and nonlinear optical characteristics of III and IV. The IV 's significant βo value (488.94 au) indicates that it has good optical and NLO qualities. Molecular docking simulation using human melatonin receptors 1 was used to better understand the binding interaction mechanism of the title compounds. In addition, ADMET evaluations were performed to establish the therapeutic potential of III and IV. [ABSTRACT FROM AUTHOR]

A series of novel pyrazolo[3,4- d ]pyrimidines bearing benzenesulfonamide moiety 5a-f, 6 and 7 were synthesized. Cytotoxic screening was conducted against MCF-7 and HepG2. 6-(4-Methoxyphenyl)-4-oxopyrazolopyrimidine derivative 5e and 4-imino-6-oxopyrazolopyrimidine derivative 6 revealed potent cytotoxic activity with IC 50 1.4 μM (MCF-7) and 0.4 μM (HepG2), respectively compared to that of doxorubicin, (IC 50 = 1.02 μM and 0.9 μM, respectively). Compounds 5e and 6 were subjected to cell cycle analysis and apoptosis assay after 24 h and 48 h treatment. Compound 5e arrested cell at G1 phase, while 6 arrested cell at S and G2/M phases, respectively. The apoptotic effect of both compounds were evidenced by pre G1 apoptosis as its percentage increased by time (7.38%, 11.61%) and (13.92%, 16.71%), respectively. Apoptosis induction capability was confirmed by the effect on early and late apoptosis and augmentation of caspase-3 level. Furthermore, compound 6 inhibited CDK2 enzyme with IC 50 = 0.19 μM and increased levels of its regulators, P21 and P27 by 10.06% and 8.5%, respectively. Moreover, a molecular docking study of compound 6 on CDK2 enzyme was adopted to explore binding interaction with amino acid residues of its active site. [ABSTRACT FROM AUTHOR]

Summary: Surveillance of wound infections has been shown to be a powerful preventive tool, and feedback to the clinical staff reduces wound infection rates. The main objectives of this study were to identify the applicability of telephone calls as a method of post-discharge wound infection surveillance, and to identify patients and procedures characteristics associated with loss for follow-up after hospital discharge. Materials and methods: This was a prospective cohort study conducted in Khartoum Teaching Hospital, Sudan. Patients, aged >18 years admitted for elective clean and clean-contaminated surgery during March 1st to 31st October 2010 were recruited. 1-month surveillance of wound infections was conducted with telephone interviews. Results: Overall 3656 patients were operated on. Of them 1769 (48.4%) were eligible {mean age 37.8+14 years; females, n =1472 (83.3%)}. The performed surgical interventions were 1814. Of these 1277 (70.4%) were clean-contaminated and 537 (29.6%) were clean. Patients who successfully completed the follow-up were 1387 (78.4%), while 368 (20.8%) were lost, and 14 (0.8%) died. The percentage of male patients (85.3%) who successfully completed the follow-up was significantly higher than females (77.8%); (P =0.002). Wound infection was detected in 15 (0.8%) cases during hospital stay and 110 (6.2%) others after hospital discharge. Conclusions: The majority of wound infections in the current study appeared in post-discharge period; this emphasis the need for establishment of surveillance program in the hospital. Surveillance of wound infections using telephone calls is applicable in this setting and can be used as an alternative method to clinic-based diagnosis of wound infections. [Copyright &y& Elsevier]

Abstract: Some new substituted coumarinylthiazolines, coumarinylthiazolidin-4-ones, and substituted chromenothiazoles were synthesized and evaluated for anticonvulsant activity. Some selected compounds were assayed against seizures induced by pentylenetetrazole (PTZ) and strychnine in mice. Compounds 3b, 6b, and 7b were the most active of the series against PTZ induced seizures. Compound 7b provided anticonvulsant activity (PD50 =95mg/kg, ip) at a dose 200mg/kg compared to phenobarbital (PD50 =16mg/kg, ip) at a dose 30mg/kg (90% protection). No clear correlation was observed between the antiepileptic activity and molecular lipophilicity descriptors of the tested compounds. [Copyright &y& Elsevier]

: ObjectivesThis study analyzed the utility of electrocardiographic (ECG) and echocardiographic findings in the diagnosis of amyloidosis proven by endomyocardial biopsy.: BackgroundCardiac amyloidosis is associated with characteristic ECG and echocardiographic changes, yet each finding alone is relatively nonspecific. A combination of noninvasive prognostic parameters would be desirable for this tissue-based diagnosis.: MethodsWe performed an analysis of 196 consecutive patients referred for endomyocardial biopsy because of clinical suspicion of cardiac amyloidosis. The diagnosis was confirmed in 58 patients (29%). The ECGs, echocardiograms, and right heart hemodynamic data were reviewed to determine which findings strongly correlate with the diagnosis. These findings were then used to build multivariate logistic regression models that predict the log-odds of having cardiac amyloidosis.: ResultsThe univariate analysis showed that low-voltage and pseudo-infarction patterns on the ECG and increased myocardial thickness and speckled-appearing myocardium on the echocardiogram were associated with biopsy-proven cardiac amyloidosis (each p < 0.01). In multivariate logistic regression models, a combination of a low voltage and measures of myocardial thickness produced the most statistically useful models. For instance, one model showed that if a low voltage was present and interventricular septal thickness is >1.98 cm, the diagnosis of cardiac amyloidosis could be made with a sensitivity of 72% and a specificity of 91%. In this model, the positive predictive and negative predictive values were 79% and 88%, respectively.: ConclusionsIn patients with suspected cardiac amyloidosis, a combination of noninvasive parameters—namely, a low voltage and increased intraventricular septal thickness—is a useful diagnostic tool. [Copyright &y& Elsevier]

Discusses the case of a male patient with necrobacillosis, an infection caused by Fusobacterium necrophorum. Lemierre syndrome variant; Inferior vena cava thrombosis and pulmonary abscesses after trauma-associated abscess in the leg; Pathogenic potential of the bacteria.

Background: To evaluate the trends in complication rates following transcatheter aortic valve replacement (TAVR) procedures according to the type of vascular approach (endovascular vs. transapical) in a large US population sample.Methods: The National Inpatient Sample (NIS) was queried for all patients diagnosed with aortic stenosis who underwent a TAVR procedure in the United States during the years 2012-2016. Outcomes assessed were peri-procedural mortality, cardiac, and non-cardiac complications. Hospitalization outcomes were modeled using logistic regression for binary outcomes and generalized linear models for continuous outcomes.Results: There were 97,320 endovascular-TAVR patients and 11,140 transapical-TAVR patients. The mean age was 80.8 years (standard error of the mean: ± 0.1). Most patients were males (53.7%) and Caucasian (87.1%). On multivariate analysis, after adjusting for age, gender, comorbidities, as well as hospital factors, patients with the transapical approach had a higher risk for mortality and adverse outcomes. Among the endovascular-TAVR group, national trends showed a diminishing incidence of procedural mortality (incidence rate ratio [IRR] 0.77; 95% CI: 0.72-0.84, p < 0.001), stroke (IRR 0.80; 95% CI: 0.73-0.87, p < 0.001), and all secondary outcomes, but no significant change in myocardial infarction. In contrast, most transapical-TAVR related procedural complications remained unchanged over time, except for a significant decrease in stroke, acute respiratory failure and need for pacemaker insertion.Conclusion: National trends show a steady increase in the number of endovascular-TAVR procedures with a concurrent decrease in procedural complications. [ABSTRACT FROM AUTHOR]

Abstract: Several analogues of the 3-substituted-2-oxoindole chemotype were synthesized by condensing isatin or the appropriate haloisatin with some amino acids or histamine under neutral conditions. All the imino derivatives produced were tested for kinase inhibitory properties against three serine/threonine kinases, namely CDK1/cyclin B, CDK5/p25 and GSK3α/β. Most of the histidine derivatives showed inhibitory properties to the three kinases in the low micromolar range. The histamine derivatives were less potent against CDK1/cyclin B and CDK5/p25 and totally inactive against GSK3α/β. So, the management of the carboxyl function may be a tool to impart selectivity in such family of kinases. Docking of 2-{[-5-bromo-2-oxoindolin-3-ylidene]amino}-3-(1H-imidazol2-yl)propanoic acid 14 to CDK5/p25 indicates that this compound can interact with the enzyme through four hydrogen bonds; for GSK/3β, the ligand poses itself in another orientation, also four hydrogen bonds can be formed between the ligand and the receptor, otherwise hydrophobic interactions seem to predominate. Also, all the final compounds were tested for their in vitro antitumor properties against MCF7 (breast), NCI-H460 (lung) and SF268 (CNS) cancer cell lines. None of the synthesized compounds was cytotoxic at 10–4 molar concentration. Moreover, compounds 13 and 14 were tested for potential antiangiogenic properties by testing their ability to inhibit the proliferation of human umbilical vein endothelial cells (HUVECs), cord formation and migration in response to chemoattractant. Only compound 14 showed moderate inhibitory properties to HUVECs proliferation and cord formation while its non-brominated derivative 13 did not. Thus, the antiangiogenesis properties are not apparently caused by inhibition of any of the tested kinases. [Copyright &y& Elsevier]

Objective: We aimed to study the impact of frailty on the outcome of transcatheter aortic valve replacement (TAVR) procedures.Methods: The National Inpatient Sample (NIS) database was queried for all patients aged ≥65 years who underwent a TAVR procedure during the years 2016-2017. Frailty was measured using a previously validated Hospital Frailty Risk Score (HFRS) scoring system. The score is ICD-10 code based; thus, it can be calculated from an administrative database. Study outcomes were in-hospital all-cause mortality, peri-procedural complications, length of stay, and total cost. Outcomes were modeled using logistic regression for binary outcomes and generalized linear regression for continuous outcomes.Results: There were 84,750 patients included in the study. These patients were divided into low-risk (61,050), intermediate-risk (22,955), and high-risk (744), based on average frailty index scores of 2, 7, and 16.8, respectively. On multivariable analysis, the HFRS correlated with increased odds for mortality with an adjusted odd ratio (a-OR) of 1.25 (95% CI: 1.22-1.29, p < 0.001), myocardial infarction [a-OR 1.10 (95% CI: 1.07-1.13, p < 0.001)], pericardiocentesis [a-OR 1.16 (95% CI: 1.12-1.20, p < 0.001)], pacemaker insertion [a-OR 1.06 (95% CI: 1.04-1.08, p < 0.001)], blood transfusion [a-OR 1.14 (95% CI: 1.11-1.16, p < 0.001)], vascular complications [a-OR 1.05 (95% CI: 1.00-1.09, p = 0.03)], longer length of stay [a-MR 1.10 (95% CI: 1.10-1.11, p < 0.001)] and higher cost [a-MR: 1.04 (95% CI: 1.03-1.04, p < 0.001)].Conclusion: The HFRS can be utilized in the risk stratification of older patients undergoing TAVR. [ABSTRACT FROM AUTHOR]

Background: Outbreaks of scabies in institutions and the socioeconomic consequences have not been reported from overpopulated countries such as Bangladesh. Study design: A community-based study among children from six residential Islamic education institutes (madrashas) in Dhaka. Multistage random sampling was used. Objectives: To study the socio-economic profile, water-sanitation facilities, personal hygiene and living conditions of these children. Methodology: Direct interviews were used to collect the data and clinical check up was performed in all children. Results: In total, 492 children received clinical check-ups; 92.5% were boys (mean age: 11.2_+ 2.4 years). 63.4% of fathers and 98.5% of mothers were either illiterate or had only received primary education, 55.1% of fathers were in tow-paid labouring jobs, and 99% of mothers were housewives. Of the 98% of children who had scabies, 71% had been re-infected (96% during the winter). Randomly assigned anti-scabies drugs revealed an average cure rate of 85.5%. Seventy-four percent of children were living in poorly ventilated buildings with overcrowded steeping arrangements. They had poor personal hygiene: 21% shared towels; 8% shared undergarments; 30% shared bed linen; and 81% kept their used clothes on a communal line or shelf. Sanitation was also poor: 39% bathed infrequently, although 97% carried out mandatory ablution. Most children (61%) washed their clothes (including undergarments) two or three times a fortnight, 35% did so every 2-3 days, and 3.7% washed their clothes on alternative days. Disease severity and re-infection were associated with infrequent washing of clothes (P<0.001) and bed linen (P<0.001), overcrowded sleeping arrangements (P<0.001) and infrequent bathing (P<0.001) with soap (P<0.001). This was further related to household income (P<0.001 for both). Conclusion: The study findings have potentially dangerous implications for public health. Immediate attention should be given to developing a sustainable tong-term intervention programme to combat scabies hyperendemicity, and to save thousands of children from impending complications. [ABSTRACT FROM AUTHOR]