Small inhibitor of Bcl-2, HA14-1, selectively enhanced the apoptotic effect of cisplatin by modulating Bcl-2 family members in MDA-MB-231 breast cancer cells

Inhibition or downregulation of Bcl-2 represents a new therapeutic approach to by-pass chemoresistance in cancer cells. Therefore, we explored the potential of this approach in breast cancer cells. Cisplatin and paclitaxel induced apoptosis in a dose-dependent manner in MCF-7 (drug-sensitive) and MDA-MB-231 (drug-insensitive) cells. Furthermore, when we transiently silenced Bcl-2, both cisplatin and paclitaxel induced apoptosis more than parental cells. Dose dependent induction of apoptosis by drugs was enhanced by the pre-treatment of these cells with HA14-1, a Bcl-2 inhibitor. Although the effect of cisplatin was significant on both cell lines, the effect of paclitaxel was much less potent only in MDA-MB-231 cells. To further understand the distinct role of drugs in MDA-MB-231 cells pretreated with HA14-1, caspases and Bcl-2 family proteins were studied. The apoptotic effect of cisplatin with or without HA14-1 pre-treatment is shown to be caspase-dependent. Among pro-apoptotic Bcl-2 proteins, Bax and Puma were found to be up-regulated whereas Bcl-2 and Bcl-x(L) were down-regulated when cells were pretreated with HA14-1 followed by paclitaxel or cisplatin. Enforced Bcl-2 expression in MDA-MB-231 cells abrogated the sensitizing effect of HA14-1 in cisplatin induced apoptosis. These results suggest that the potentiating effect of HA14-1 is drug and cell type specific and may not only depend on the inhibition of Bcl-2. Importantly, alteration of other pro-apoptotic or anti-apoptotic Bcl-2 family members may dictate the apoptotic response when HA14-1 is combined with chemotherapeutic drugs

Hiccup Due to Aripiprazole Plus Methylphenidate Treatment in an Adolescent with Attention Deficit and Hyperactivity Disorder and Conduct Disorder: A Case Report

Our case had hiccups arising in an adolescent with the attention deficit and hyperactivity disorder (ADHD) and conduct disorder (CD) after adding aripiprazole treatment to extended-release methylphenidate. Actually, antipsychotics are also used in the treatment of hiccups, but studies suggest that they can cause hiccups as well. Within 12 hours of taking 2.5 mg aripiprazole added to extended-release methylphenidate at a dose of 54 mg/day, 16-year-old boy began having hiccups in the morning, which lasted after 3-4 hours. As a result, aripiprazole was discontinued and methylphenidate was continued alone because we could not convince the patient to use another additional drug due to this side effect. Subsequently, when his behavior got worsened day by day, his mother administered aripiprazole alone again at the dose of 2.5 mg/day at the weekend and continued treatment because hiccup did not occur again. But when it was administered with methylphenidate on Monday, hiccup started again next morning and lasted one hour at this time. In conclusion, we concluded that concurrent use of methylphenidate and aripiprazole in this adolescent led to hiccups

A wideband linear tunable CDTA and its application in field programmable analogue array

This document is the Accepted Manuscript version of the following article: Hu, Z., Wang, C., Sun, J. et al. ‘A wideband linear tunable CDTA and its application in field programmable analogue array’, Analog Integrated Circuits and Signal Processing, Vol. 88 (3): 465-483, September 2016. Under embargo. Embargo end date: 6 June 2017. The final publication is available at Springer via https://link.springer.com/article/10.1007%2Fs10470-016-0772-7 © Springer Science+Business Media New York 2016In this paper, a NMOS-based wideband low power and linear tunable transconductance current differencing transconductance amplifier (CDTA) is presented. Based on the NMOS CDTA, a novel simple and easily reconfigurable configurable analogue block (CAB) is designed. Moreover, using the novel CAB, a simple and versatile butterfly-shaped FPAA structure is introduced. The FPAA consists of six identical CABs, and it could realize six order current-mode low pass filter, second order current-mode universal filter, current-mode quadrature oscillator, current-mode multi-phase oscillator and current-mode multiplier for analog signal processing. The Cadence IC Design Tools 5.1.41 post-layout simulation and measurement results are included to confirm the theory.Peer reviewedFinal Accepted Versio

Gestational diabetes mellitus is as innocent as you think?

Background: We aimed to compare fetal outcomes, fetal hypoxia, acidemia and maternal chracteristics including hemoglobin A1c, doppler indices between gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (DM) among pregnant women treated with insulin.Methods: Data of pregnant patients with diagnosis of pregestational diabetes (type 1 and 2) and GDM who were treated with insulin (GDM A2 in White classification) was retrospectively collected and compared. Patients with active chronic systemic disease, multiple pregnancies, lost to follow up and detected fetal malformations were exluded. Maternal characteristics, umbilical doppler indices and amnion fluid index, gestational age at delivery, delivery characteristics (including vaginal delivery, or cesarean section) and newborn characteristics such as birth weight, Apgar score and umblical cord pH were all recorded.Results: A total of 130 patients (67 patients with GDM and 63 pregestational DM) were recruited to the study. There were no significant difference regarding type of delivery, fetal birth weight, umbilical cord Hb and gestational birth age. No other significant difference in frequency of low Apgar scores and fetal acidosis or metabolic acidosis were reported. HbA1c and blood glucose levels and insulin dosage were significantly statistically higher in pregestational group.Conclusions: The frequency of fetal distress parameters and poor fetal outcome were similar between groups although pregestaional diabetic patients had higher HbA1c rates. Therefore, patients with GDM (A2) should be followed up as closely as pregestational (overt) diabetic patients

Urban Insecurity and Security Expenditures in Turkiye

The majority of the world\u27s population now lives in urban areas, making cities targets of warfare and areas of insecurity in recent years. This has led to a growing interest in urban security and a shift towards the militarization of traditional police forces. However, the relationship between urban security and securitization is not well understood in the literature, and research on the implications of public resource allocation is limited. This study aims to investigate the effectiveness of public security spending in reducing insecurity in urban areas in Turkey, against the backdrop of increased securitization in the 2000s. The study uses data from 81 provinces between 2010 and 2018 and constructs two alternative indicators of insecurity. The results show that an increase in security spending reduces provincial insecurity, while public-private wage inequality and out-migration from insecure provinces increase insecurity. The paper discusses the implications of these findings for democracy and human rights

Emerging potential of tumor treating fields as a treatment modality for pancreatic cancer: a narrative review of therapeutic evolution

Background and Objective: Pancreatic ductal adenocarcinoma (PDAC) is poorly responsive to conventional treatment and therefore is among the deadliest cancers. Tumor treating fields (TTFields) delivers low-intensity electrical fields that alternate in direction and frequency to disrupt cell division in cancer cells and has emerged as a potentially effective therapy for PDAC. In this narrative review, we discuss the primary mechanisms of TTFields as well as emerging preclinical and clinical outcomes of this novel technology for PDAC. Methods: We performed a literature search on PubMed, Clinicaltrials.gov and Google Scholar using the terms “tumor treating fields” and “pancreatic ductal adenocarcinoma”. We included studies, review articles and editorials published in English between 1st January 2000 and 5th January 2023. All papers reviewed and their key references are cross-checked to maintain a balanced and high-quality literature review on the subjects. Key Content and Findings: Preclinical studies have demonstrated anti-mitotic effects of TTFields on PDAC cell lines, and the safety of TTFields has been demonstrated in a phase II study. An ongoing phase III trial of chemotherapy +/− TTFields will hopefully provide valuable insights into whether TTFields should become a standard of care (SOC) for locally advanced unresectable pancreatic cancer. Thus, TTFields could represent a major breakthrough in the treatment of this highly malignant disease. Conclusions: Preliminary clinical findings suggest that TTFields could be a promising treatment option for patients with PDAC, given its favorable safety profile and potential for significant clinical benefit. However, further research is needed to determine the optimal treatment parameters and patient subgroups that may benefit the most from this therapy

Warning Students of the Consequences of Examination Failure: An Effective Strategy for Promoting Student Engagement?

In the context of high-stakes qualifications, teachers may warn students of the negative consequences of failure as a tactic designed to increase engagement and ultimately achievement. Previous studies have shown that these types of messages, namely fear appeals, are indirectly related to engagement and achievement in different ways depending on how they are evaluated by the student. When fear appeals are evaluated as a challenge, they are positively related to engagement and achievement. When evaluated as a threat, fear appeals are negatively related to engagement and achievement. In the present study, we offer a robust test of these relations in a multi-level model that controls for autoregressive and concurrent relations in the domain of mathematics. Self-reported data were collected from 1,530 participants, aged 14-16 years, at two time points over the final two years of secondary education. These data were linked to prior and subsequent achievement. Results showed that students who attended to fear appeals and evaluated them as a challenge showed higher subsequent engagement, and students who showed higher engagement showed higher achievement. Accordingly, it may be beneficial to identify those students likely to evaluate fear appeals as a threat and intervene in order to enhance the likelihood of a challenge evaluation (e.g., building confidence through strategy focused feedback and strengthening beliefs in the value of effort). Given the difficulties associated with teachers judging students’ motivation and emotion as private experiences, methods to access student voice should be considered