DnaB and DciA: Mechanisms of Helicase Loading and Translocation on ssDNA.

Replicative helicases are assembled on chromosomes by helicase loaders before initiation of DNA replication. Here, we investigate mechanisms used by the bacterial DnaB replicative helicase and the DciA helicase loader. In the present structure of the DnaB-ssDNA•ATPγS complex, the amino-terminal (NTD) tier, previously found as an open spiral in a GDP•AlF4 complex, was observed to adopt a closed planar arrangement.

Therapeutic potential of natural products in inflammation: underlying molecular mechanisms, clinical outcomes, technological advances, and future perspectives.

Chronic inflammation is a common underlying factor in many major diseases, including heart disease, diabetes, cancer, and autoimmune disorders, and is responsible for up to 60% of all deaths worldwide. Metformin, statins, and corticosteroids, and NSAIDs (non-steroidal anti-inflammatory drugs) are often given as anti-inflammatory pharmaceuticals, however, often have even more debilitating side effects than the illness itself. The natural product-based therapy of inflammation-related diseases has no adverse effects and good beneficial results compared to substitute conventional anti-inflammatory medications.

Novel Hybrid Indole-Based Caffeic Acid Amide Derivatives as Potent Free Radical Scavenging Agents: Rational Design, Synthesis, Spectroscopic Characterization, In Silico and In Vitro Investigations.

Antioxidant small molecules can prevent or delay the oxidative damage caused by free radicals. Herein, a structure-based hybridization of two natural antioxidants (caffeic acid and melatonin) afforded a novel hybrid series of indole-based amide analogues which was synthesized with potential antioxidant properties. A multiple-step scheme of in vitro radical scavenging assays was carried out to evaluate the antioxidant activity of the synthesized compounds.

Omarigliptin Mitigates 6-Hydroxydopamine- or Rotenone-Induced Oxidative Toxicity in PC12 Cells by Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Actions.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are reported to exhibit promising effects on several pathological processes associated with Parkinson's disease (PD). To explore its repositioning potential as an antiparkinsonian agent, we evaluated the effects of omarigliptin (OMG), a DPP-4 inhibitor recently approved as a hypoglycemic drug, on neurotoxin-induced toxicity, using PC12 cells as a cellular model of PD. The molecular mechanism(s) underlying its protective activity was also investigated.

Ultrasound-guided lumbar erector spinae plane block versus caudal block for postoperative analgesia in pediatric hip and proximal femur surgery: a randomized controlled study.

Background: According to previous research, 20% of infants experience prolonged postsurgical pain 6-12 months after major surgery, which is linked to functional impairment and a lower quality of life. The aim of our study is to evaluate whether the analgesic effect of the erector spinae plane block (ESPB) is superior to that of caudal epidural anesthesia (CEA) in pediatric patients undergoing hip or proximal femoral surgeries.

Methods: Seventy-six children ranging in age from 1 to 7 years scheduled for hip or proximal femur surgery were randomly assigned to receive either a unilateral ultrasound-guided ESPB or CEA with bupivacaine 0.

The impact of COVID-19 vaccination on glycaemic control in children and adolescents with type 1 diabetes mellitus on continuous glucose monitoring.

Aims: To investigate the impact of SARS-COV-2 vaccination on the glycaemic control in children and adolescents with T1DM wearing continuous glucose monitoring (CGM).

Methods: Caregivers of children and adolescents with T1DM were questioned regarding SARS-CoV-2 vaccination during their regular visits at the Pediatric Diabetes Outpatient Clinic. Data regarding Time in Range (TIR) (glucose levels: 70-180 mg/dl) 7 days prior and 7 days after a vaccination dose were collected in patients wearing CGM and data regarding insulin daily doses were also obtained for the insulin pump users.

Novel cudraisoflavone J derivatives as potent neuroprotective agents for the treatment of Parkinson's disease via the activation of Nrf2/HO-1 signaling.

Parkinson's disease (PD) is a neurodegenerative disorder that causes uncontrollable movements. Although many breakthroughs in PD therapy have been accomplished, there is currently no cure for PD, and only trials to relieve symptoms have been evaluated. Recently, we reported the total synthesis of cudraisoflavone J and its chiral isomers [Lu et al.

Impact of and Gene Expressions on Prognosis and Treatment Response in Acute Myeloid Leukemia Patients.

Introduction: Acute myeloid leukemia (AML) is the most common type of leukemia among adults and is characterized by various genetic abnormalities. and are promising markers of AML. Our objective is to assess the potential roles of and as prognostic and predictive markers in newly diagnosed AML patients and determine the correlation between their expressions and other prognostic markers as mutations, response to treatment, and patient's survival.

Hair Follicle-Related MicroRNA-34a Serum Expression and rs2666433A/G Variant in Patients with Alopecia: A Cross-Sectional Analysis.

Alopecia areata (AA) is a type of immune-mediated alopecia. Recent studies have suggested microRNAs’ (miRNAs) implication in several cellular processes, including epidermal and hair follicle biology. Single nucleotide polymorphisms (SNPs) can modify gene expression levels, which may induce an autoimmune response.

[Effects of Monitoring "Out-of-Area" Vaccinated Children on Data Quality, San Pedro Health District, Côte D'ivoire in 2019].

In order to improve the quality of vaccination data from the health centers, we carried out the follow-up of "out-of-area" children, vaccinated in the district of San Pedro. The objective of this work was to measure the effects of taking into account the "out-of-area" vaccinated children on the quality of the data and the immunization performance of the health centers. This monitoring, which was carried out between March and August 2019, consisted of four steps: the vaccination of "out-of-area" children by the health center, the monthly update in the register of the status of vaccinated "out-of-area" children, the accounting of these children, and the re-evaluation of the health center's vaccine performance.

Emerging Therapeutic Strategies for Parkinson's Disease and Future Prospects: A 2021 Update.

Parkinson's disease (PD) is a neurodegenerative disorder pathologically distinguished by degeneration of dopaminergic neurons in the substantia nigra pars compacta. Muscle rigidity, tremor, and bradykinesia are all clinical motor hallmarks of PD. Several pathways have been implicated in PD etiology, including mitochondrial dysfunction, impaired protein clearance, and neuroinflammation, but how these factors interact remains incompletely understood.

The Use of Transesophageal Doppler and Central Venous Oxygen Saturation as Predictors of Weaning Success.

Objectives: Weaning individuals from mechanical ventilation (MV) is a challenge to physicians. Respiratory failure is the main reason for weaning failure (WF), but heart failure plays a pivotal role as well. Transesophageal Doppler (TED) is a minimally invasive method of hemodynamic tracking with fewer problems.

Highly Potent, Selective, and Competitive Indole-Based MAO-B Inhibitors Protect PC12 Cells against 6-Hydroxydopamine- and Rotenone-Induced Oxidative Stress.

Monoamine oxidase B (MAO-B) is responsible for dopamine metabolism and plays a key role in oxidative stress by changing the redox state of neuronal and glial cells. To date, no disease-modifying therapy for Parkinson's disease (PD) has been identified. However, MAO-B inhibitors have emerged as a viable therapeutic strategy for PD patients.

Melatonin Analogues Potently Inhibit MAO-B and Protect PC12 Cells against Oxidative Stress.

Monoamine oxidase B (MAO-B) metabolizes dopamine and plays an important role in oxidative stress by altering the redox state of neuronal and glial cells. MAO-B inhibitors are a promising therapeutical approach for Parkinson's disease (PD). Herein, 24 melatonin analogues (-) were synthesized as novel MAO-B inhibitors with the potential to counteract oxidative stress in neuronal PC12 cells.

Discovery of 3,4-dichloro-N-(1H-indol-5-yl)benzamide: A highly potent, selective, and competitive hMAO-B inhibitor with high BBB permeability profile and neuroprotective action.

Since there is no disease-modifying treatment discovered yet for Parkinson's disease (PD), there is still a vital need to develop novel selective monoamine oxidase B (MAO-B) inhibitors as promising therapeutically active candidates for PD patients. Herein, we report the design, synthesis, and full characterization of new twenty-six indole derivatives as potential human MAO-B (hMAO-B) selective inhibitors. Six compounds (2i, 3b-e, and 5) exhibited low micromolar to nanomolar inhibitory activities over hMAO-B; compared to our recently reported N-substituted indole-based lead compound VIII (hMAO-B IC = 777 nM), compound 5 (3,4-dichloro-N-(1H-indol-5-yl)benzamide) exhibited 18-fold increase in potency (IC = 42 nM).

Implementation of a pooled surveillance testing program for asymptomatic SARS-CoV-2 infections in K-12 schools and universities.

Background: The negative impact of continued school closures during the height of the COVID-19 pandemic warrants the establishment of cost-effective strategies for surveillance and screening to safely reopen and monitor for potential in-school transmission. Here, we present a novel approach to increase the availability of repetitive and routine COVID-19 testing that may ultimately reduce the overall viral burden in the community.

Methods: We implemented a testing program using the SalivaClear࣪ pooled surveillance method that included students, faculty and staff from K-12 schools (student age range 5-18 years) and universities (student age range >18 years) across the country (Mirimus Clinical Labs, Brooklyn, NY).

MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis.

Toll-like receptor (TLR) family signature has been implicated in sepsis etiopathology. We aimed to evaluate the genetic profile of TLR pathway-related key genes; the myeloid differentiation protein 88 (MYD88), IL1 receptor-associated kinase 1 (IRAK1), the nuclear factor kappa-B1 (NFKB1), and interleukin 6 (IL6) in the blood of neonates with sepsis at the time of admission and post-treatment for the available paired-samples. This case-control study included 124 infants with sepsis admitted to the neonatal intensive care unit and 17 controls.

Impact of cytotoxic T-lymphocyte-associated protein 4 codon 17 variant and expression on vitiligo risk.

Background: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is one of the essential brakes expressed on T cells that prevent T-cell hyperactivation-associated autoimmune disorders. Several CTLA4 polymorphisms were implicated in the regulation of gene expression. We aimed to explore the association of CTLA4 expression and rs231775 (c.

Safety and Duration of Low-Dose Adjuvant Dexamethasone in Regional Anesthesia for Upper Extremity Surgery: A Prospective, Randomized, Controlled Blinded Study.

Background: Orthopedic procedures concerning the upper extremity commonly use a brachial plexus nerve block to achieve postoperative analgesia. The addition of dexamethasone to peripheral nerve blocks has been shown to significantly prolong its effect. We hypothesize that 1 mg doses of dexamethasone will prolong brachial plexus nerve block with similar efficacy to 4 mg and better than ropivacaine alone.

A Multimodal Pain Management Regimen for Open Treatment of Distal Radius Fractures: A Randomized Blinded Study.

Background: Adequate pain control is critical after outpatient surgery where patients are not as closely monitored. A multimodal pain management regimen was compared to a conventional pain management method in patients undergoing operative fixation for distal radius fractures. We hypothesized that there would be a decrease in the amount of narcotics used by the multimodal group compared to the conventional pain management group, and that there would be no difference in bone healing postoperatively.

Association of microRNA 17 host gene variant (rs4284505) with susceptibility and severity of systemic lupus erythematosus.

Objective: MicroRNAs are large family clusters of small noncoding RNAs that implicated in genetic and epigenetic regulation of several immunological processes and pathways. As an epigenetic modifier, the microRNA 17-92 cluster host gene (MIR17HG) has been shown to regulate the expression of genes involved in systemic lupus erythematosus (SLE) pathway. This study aimed to explore the association of MIR17HG (rs4284505; A>G) variant with SLE development and phenotype in a sample of the Eastern Mediterranean population.

Generation and Profiling of 2,135 Human ESC Lines for the Systematic Analyses of Cell States Perturbed by Inducing Single Transcription Factors.

Transcription factors (TFs) play a pivotal role in determining cell states, yet our understanding of the causative relationship between TFs and cell states is limited. Here, we systematically examine the state changes of human pluripotent embryonic stem cells (hESCs) by the large-scale manipulation of single TFs. We establish 2,135 hESC lines, representing three clones each of 714 doxycycline (Dox)-inducible genes including 481 TFs, and obtain 26,998 microscopic cell images and 2,174 transcriptome datasets-RNA sequencing (RNA-seq) or microarrays-48 h after the presence or absence of Dox.

Author Correction: Genotypic characterization of multiple drug resistant Escherichia coli isolates from a pediatric cancer hospital in Egypt.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genotypic characterization of multiple drug resistant Escherichia coli isolates from a pediatric cancer hospital in Egypt.

Infection with multiple drug resistant (MDR) Escherichia coli poses a life threat to immunocompromised pediatric cancer patients. Our aim is to genotypically characterize the plasmids harbored in MDR E. coli isolates recovered from bacteremic patients of Children's Cancer Hospital in Egypt 57357 (CCHE 57357).

[Performance of the Strategy to Catch Up with Drop Out and Unvaccinated Children in Côte d'Ivoire in 2018].

To improve the performance of Côte-d'Ivoire's immunization program, we have implemented a strategy to catch up with drop out children (DOC) and unvaccinated children (UVC) in 14 Health Districts (HDs) with the lowest measles vaccination coverage. This article presents the effectiveness and cost of this strategy. We selected the areas with the highest numbers of DOC: 5 health areas (HAs) per HD and 5 villages/neighborhoods per HA.