Antibacterial activity of flavonoids and their structure–activity relationship: An update review

Based on World Health Organization reports, resistance of bacteria to well‐known antibiotics is a major global health challenge now and in the future. Different strategies have been proposed to tackle this problem including inhibition of multidrug resistance pumps and biofilm formation in bacteria and development of new antibiotics with novel mechanism of action. Flavonoids are a large class of natural compounds, have been extensively studied for their antibacterial activity, and more than 150 articles have been published on this topic since 2005. Over the past decade, some promising results were obtained with the antibacterial activity of flavonoids. In some cases, flavonoids (especially chalcones) showed up to sixfold stronger antibacterial activities than standard drugs in the market. Some synthetic derivatives of flavonoids also exhibited remarkable antibacterial activities with 20‐ to 80‐fold more potent activity than the standard drug against multidrug‐resistant Gram‐negative and Gram‐positive bacteria (including Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus). This review summarizes the ever changing information on antibacterial activity of flavonoids since 2005, with a special focus on the structure–activity relationship and mechanisms of actions of this broad class of natural compounds.     

Surgeon Volume and Outcomes in Benign Hysterectomy

Annual surgeon case volume has been linked to patient outcome in a variety of surgical fields, although limited data focus on gynecologic surgery performed by general gynecologists. Herein we review the literature addressing the associations between intraoperative injury, postoperative morbidity, and resource use among surgeons performing a low vs high volume of hysterectomies. Although study design and populations differ, individual and composite morbidity outcomes consistently favored high-volume surgeons. Given the growing emphasis on competency-based evaluation in surgery, gynecology departments may soon consider volume requirements a component of privileging.     

Delayed extinction fails to reduce skin conductance reactivity to fear‐conditioned stimuli

A brief 10‐min time delay between an initial and subsequent exposure to extinction trials has been found to impair memory reconsolidation in fear‐conditioned rodents and humans, providing a potential means to reduce fearfulness in anxiety disorders and posttraumatic stress disorder (PTSD). The present study used videos of biologically prepared, conditioned stimuli (tarantulas) to test the efficacy of delayed extinction in blocking reconsolidation of conditioned fear in healthy young adults. Strong differential conditioning, measured by skin conductance, was observed among a screened subset of participants during acquisition. However, the delayed‐extinction intervention failed to reduce reactivity to the conditioned stimulus paired with the extinction delay. These results are partially consistent with other recent, mixed findings and point to a need for testing other candidate interventions designed to interfere with the reconsolidation process.     

The accuracy of the rectovaginal examination in detecting cul-de-sac disease in patients under general anaesthesia

BACKGROUND: The rectovaginal examination is frequently used as an adjunct to a bimanual examination. The accuracy of rectovaginal examination in detecting cul-de-sac disease under ideal circumstances of the operating room was studied. METHODS: Fifty-two attending physicians and 30 residents were selected on experience and immediate availability to evaluate the presence of uterosacral nodularity and external rectal compression on 140 women undergoing general anaesthesia, followed by laparoscopy or laparotomy, at an academic medical centre. Physicians were masked to the indications for surgery and procedure ranging from diagnostic laparoscopy to laparotomy for suspected malignancy. RESULTS: Mean patient body mass index (BMI) was 26.1 kg/m2 and nearly one-third had had previous surgery. Based on the surgical findings, cul-de-sac disease was common, including uterosacral nodularity (5.8%) and rectal compression (10.1%). Both sensitivity and positive predictive value of the rectovaginal examination for detecting uterosacral nodularity were zero, whereas specificity approached 95%. Accuracy in detecting rectal compression was somewhat better with a sensitivity of 34%, specificity 96.7% and positive predictive value 55.6%. Neither examiner-years of experience nor the laterality of the dominant or examining hand affected the accuracy of the rectovaginal examination. CONCLUSIONS: The rectovaginal examination has marked limitations despite the controlled circumstances of the operating room including general anaesthesia, an empty bladder and ideal patient positioning. As suspected, the specificity of the rectal examination is high due to the low prevalence of disease. However, the sensitivity of the rectovaginal examination is very low, limiting its capacity as a screening test.     

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

In respect to the enhanced incidence rate of cancer worldwide, studies have focused on cancer therapy using novel strategies. Chemotherapy is a common strategy in cancer therapy, but its adverse effects and chemoresistance have limited its efficacy. So, attempts have been directed towards minimally invasive cancer therapy using plant derived‐natural compounds. Cryptotanshinone (CT) is a component of salvia miltiorrihiza Bunge, well‐known as Danshen and has a variety of therapeutic and biological activities such as antioxidant, anti‐inflammatory, anti‐diabetic and neuroprotective. Recently, studies have focused on anti‐tumor activity of CT against different cancers. Notably, this herbal compound is efficient in cancer therapy by targeting various molecular signaling pathways. In the present review, we mechanistically describe the anti‐tumor activity of CT with an emphasis on molecular signaling pathways. Then, we evaluate the potential of CT in cancer immunotherapy and enhancing the efficacy of chemotherapy by sensitizing cancer cells into anti‐tumor activity of chemotherapeutic agents, and elevating accumulation of anti‐tumor drugs in cancer cells. Finally, we mention strategies to enhance the anti‐tumor activity of CT, for instance, using nanoparticles to provide targeted drug delivery.     

External and internal radiation therapy: past and future directions

Cancer is a leading cause of morbidity and mortality in the modern world. Treatment modalities comprise radiation therapy, surgery, chemotherapy and hormonal therapy. Radiation therapy can be performed by using external or internal radiation therapy. However, each method has its unique properties which undertakes special role in cancer treatment, this question is brought up that: For cancer treatment, whether external radiation therapy is more efficient or internal radiation therapy one? To answer this question, we need to consider principles and structure of individual methods. In this review, principles and application of each method are considered and finally these two methods are compared with each other.     

Design, synthesis, and incorporation of a beta-turn mimetic in angiotensin II forming novel pseudopeptides with affinity for AT1 and AT2 receptors

A benzodiazepine-based beta-turn mimetic has been designed, synthesized, and incorporated into angiotensin II. Comparison of the mimetic with beta-turns in crystallized proteins showed that it most closely resembles a type II beta-turn. The compounds exhibited high to moderate binding affinity for the AT2 receptor, and one also displayed high affinity for the AT1 receptor. Molecular modeling showed that the high-affinity compounds could be incorporated into a previously derived model of AT2 receptor ligands.     

TP53 Gene Pro72Arg (rs1042522) Single Nucleotide Polymorphism as Not a Risk Factor for Colorectal Cancer in the Iranian Azari Population

Background: The p53 protein participates critically in several cellular functions such as cell growth and DNA repair. Polymorphisms in the TP53 locus have repeatedly been implicated in the pathogenesis of cancers all over the world. Over 200 single nucleotide polymorphisms (SNPs) have been characterized, but one well-known example at at codon 72, Pro72Arg (rs1042522), has the displayed inconsistent results with regard to cancer risk. Herein, we aimed to evaluate whether Pro72Arg (rs1042522) single nucleotide polymorphism (SNP) in TP53 gene might be associated with risk of colorectal cancer in the Iranian Azari population. Methods: Blood samples were taken from 100 healthy controls and 100 colorectal cancer patients with Iranian-Azeri ethnicity. Genotyping was performed with Tetra-ARMS PCR. Results: The alleles of the TP53 gene Pro72Arg SNP did not significantly differ in prevalence between patients and controls (P>0.05). Additionally, genotypes of Pro72Arg SNP were not significantly associated with colorectal cancer risk in the studied population. Conclusions: Pro72Arg SNP of TP53 gene may not be involved in the disease pathogenesis in Iranian Azari patients with colorectal cancer.     

Randomized controlled experimental study of hydrocortisone and D-cycloserine effects on fear extinction in PTSD

Fear extinction underlies prolonged exposure, one of the most well-studied treatments for posttraumatic stress disorder (PTSD). There has been increased interest in exploring pharmacological agents to enhance fear extinction learning in humans and their potential as adjuncts to PE. The objective of such adjuncts is to augment the clinical impact of PE on the durability and magnitude of symptom reduction. In this study, we examined whether hydrocortisone (HC), a corticosteroid, and D-Cycloserine (DCS), an N-methyl-D-aspartate receptor partial agonist, enhance fear extinction learning and consolidation in individuals with PTSD. In a double-blind placebo-controlled 3-group experimental design, 90 individuals with full or subsyndromal PTSD underwent fear conditioning with stimuli that were paired (CS+) or unpaired (CS−) with shock. Extinction learning occurred 72 h later and extinction retention was tested one week after extinction. HC 25 mg, DCS 50 mg or placebo was administered one hour prior to extinction learning. During extinction learning, the DCS and HC groups showed a reduced differential CS+/CS− skin conductance response (SCR) compared to placebo (b = −0.19, CI = −0.01 to −37, p = 0.042 and b = −0.25, CI = −08 to −0.43, p = 0.005, respectively). A nonsignificant trend for a lower differential CS+/CS− SCR in the DCS group, compared to placebo, (b = −0.25, CI = 0.04 to −0.55, p = 0.089) was observed at retention testing, one week later. A single dose of HC and DCS facilitated fear extinction learning in participants with PTSD symptoms. While clinical implications have yet to be determined, our findings suggest that glucocorticoids and NMDA agonists hold promise for facilitating extinction learning in PTSD.Subject terms: Post-traumatic stress disorder, Fear conditioning     

The application of the linear quadratic model to compensate the effects of prolonged fraction delivery time on a Balb/C breast adenocarcinoma tumor: An in vivo study

Purpose To investigate the effect of increasing the overall treatment time as well as delivering the compensating doses on the Balb/c breast adenocarcinoma (4T1) tumor.

Materials and methods A total of 72 mice were divided into two aliquots (classes A and B) based on the initial size of their induced tumor. Each class was divided into a control and several treatment groups. Among the treatment groups, group 1 was continuously exposed to 2 Gy irradiation, and groups 2 and 3 received two subfractions of 1 Gy over the total treatment times of 30 and 60 min, respectively. To investigate the effect of compensating doses, calculated based on the developed linear quadratic model (LQ) model, the remaining two groups (groups 4 and 5) received two subfractions of 1.16 and 1.24 Gy over the total treatment times of 30 and 60 min, respectively. The growing curves, Tumor Growth Time (TGT), Tumor Growth Delay Time (TGDT) and the survival of the animals were studied.

Results For class A (tumor size?≤?30?mm³), the average tumor size in the irradiated groups 1–5 was considerably different compared to the control group as one unit (day) change in time, by amount of??160.8,??158.9,?+39.4 and?+44.0, respectively. While these amounts were?+22.0,?+17.9,??21.7 and??0.1 for class B (tumor size?≥?400?mm³). For the class A of animals, the TGT and TGDT parameters were significantly lower (0?≤?0.05) for the groups 2 and 3, compared to group 1. There was no significant difference (p?>?0.05) between groups 1, 4 and 5 in this class. There was no significant difference (p?>?0.05) between all the treated groups in class B.

Conclusions Increasing total treatment time affects the radiobiological efficiency of treatment especially in small-sized tumor. The compensating doses derived from the LQ model can be used to compensate the effects of prolonged treatment times at in vivo condition.