Anticancer activities of selected Emirati Date (Phoenix dactylifera L.) varieties pits in human triple negative breast cancer MDA-MB-231 cells

The date palm (Phoenix dactylifera L.) is an important fruit crop with significant pharmaceutical potential. Little data are available on comparative pharmaceutical importance of the date pits. We designed this study to assess the antitumorigenic effects of date palm pits extracts from different Emiratis varieties. We used MDA-MB-231 cells derived from triple negative breasts cancer tissues as a model. We found that out of the 17 date pits extracts from 6 Emiratis varieties, three (Khalas extract in water + acetone (1:1), Abu-Maan extract in MeOH + Chloroform (1:1) and Mabroom extract in water + acetone (1:1)) were found effectively cytotoxic and changed morphology of cells in dose and time dependent manner. We found the maximum effect at 2.5 mg/mL concentration at 72 h. We calculated IC50 values for these varieties at 24 h. IC50 values for Khalas, Abu-Maan and Mabroom were 0.982 mg/mL, 1.149 mg/mL and 2.213 mg/mL respectively. We treated the cells with IC50 values of extracts and observed changes in protein profile using human kinase array kit. After analyzing the results, we suggest that EGFR/ERK/FAK pathway, eNOS and src family proteins are targets of these extracts. We conclude that date pits extracts can be a possible therapeutic agent against cancer and we suggest further studies

Simple and sensitive chromatographic method development for in-vitro and in-vivo analysis of doxorubicin-loaded poly lactic-co-glycolic acid nanoparticles

Purpose: To develop a bioanalytical high performance liquid chromatography (HPLC) method for the quantification of doxorubicin in biological fluids and polymeric nano-formulations. Methods: Analysis of doxorubicin in polymeric nanoparticles and biological samples was carried out at 252 nm using Purospher® RP-18 end-capped column (250mm×4.6mm,5µm) secured with a guard column cartridge RP18 (30mm×4.6mm,10µm). The mobile phase used was 0.025M phosphate buffer and acetonitrile (ACN) (65:35, v:v) in isocratic mode at a flow rate of 0.9 ml/min, run time of 10 min, column oven temperature of 30 °C, and injection volume of 40 μL. Results: The standard curve for doxorubicin was linear (0.999) in the concentration range of 0.022 - 1.00 μg/mL in human and albino mice plasma. Nominal retention times of doxorubicin and IS were 3.5 and 5.5 min, respectively. Mean recovery was within acceptable limits (100 ± 2 %). The limit of detection (LOD) and limit of quantification (LOQ) were 0.012 and 0.022 μg/mL, respectively. Conclusion: A reliable HPLC method has been successfully developed, validated and applied for the in vitro analysis of doxorubicin released from polymeric nanoparticles and in vivo pharmacokinetic studies in albino mice. The method may also be applicable to the analysis of doxorubicin in human fluids

Surgical Outcome of Open Carpal Tunnel Release Using Global Symptom Severity Score

Objective:  Purpose of conducting this study was to evaluate the surgical outcome of open carpal tunnel release using Global Symptom Severity score (GSS) in our local setting. Material and Methods:  This prospective analytical study was conducted in the Neurosurgery Department Hayatabad Medical Complex, Peshawar. We operated consecutive 105 Carpal tunnel syndrome cases over a period of 2 years via open carpal tunnel release (OCTR) method. All of these cases were surgically indicated. All patients were evaluated preoperatively with clinical assessment and NCS. Cases were operated under local anesthesia as a day case surgery. Patients were evaluated at 3 months follow-up visit using global symptom severity score (GSS) and compared with pre operative GSS. The paired sample test was applied to obtain p value. Results:  Total 105 patients were operated during study period. 72 (69%) patients were women and 33 (31%) were men. The mean age of patients was 41 years. 70 (66.66%) procedures were done for the right hand and 35 (33.33%) were performed for left hand. Pre-op Mean GSS score was 27 ± 2.5 which decreased to 2.1 ± 0.43 postoperatively (P < 0.005). Conclusion:  Carpal tunnel syndrome is more commonly affecting the dominant hand of middle aged females. Open carpal tunnel release procedure is the safe and effective treatment for this compressive neuropathy

An Efficient Classification of Emotions in Students\u27 Feedback using Deep Neural Network

Background and Objective: In both the corporate and academic worlds, the collection and analysis of feedback (product evaluation, social media debate, and student input) has long been a significant topic. The traditional approaches to collect student feedback focused on data collection and analysis via questionnaires. However, the student makes comments on social media sites that need to be looked at to improve educational standards at schools.Methods: The purpose of this work is to construct a deep neural network-based system to assess students\u27 feedback and emotions found in the reviews. Our approach applies a Deep Learning-based Bi-LSTM Model to a benchmark student input dataset. It would categorize students\u27 feedback about their instructors according to their emotional states, such as love, happiness, fury, and disdain.Results: The experimental findings demonstrate that the proposed approach outperforms both benchmark studies and state-of-the-art machine learning classifiers

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Dysregulation of wnt/beta-catenin pathway in pituitaryadenomas and its stimulation by CRH and inhibition bySRIF in ACTH-secreting pituitary adenomas

Hintergrund und Ziele: Der Wnt-Signalweg spielt eine Rolle bei der Kontrolle der Zellproliferation und Differenzierung in vielen Geweben, einschließlich des Hormonsystems. Dieser Signalweg wurde auch in verschiedenen Tumorarten nachgewiesen. Allerdings ist nur wenig über die Wnt-Signalkaskade in Hypophysenzellen und bei der Tumorgenese bekannt. Diese arbeit diente dazu die stellung und die regulation des Wnt/β-catenin Signalweg in hypophyseal adenomen aufzuklären. Methoden: Um die Rolle des Wnt/β-catenin Signalweg in Hypophysenadenomen zu untersuchen, wurde die Expression der folgenden Proteine analysiert: β-Catenin, TCF-4 und Cyclin D1 in GH absondernden-, Null-zell- und ACTH absondernden Hypophysenadenomen. Effekte von CRH und SRIF auf des Wnt/β-catenin Signalweg wurden in AtT-20 zellen und GH-3 zellen. Für mRNA- expression rtPCR, für Protein-expression Westernblotten, für zelluläre lokalisation immunocytochemie, für β-Catenin/TCF-4 complex bildung immunoprecipitation wurden verwendet. Darüberhinaus wurde die zell proliferation mittels eines MTT Assay gemessen. Ergebnisse und Beobachtungen: Die Expression aller drei Proteine variierte stark innerhalb der Gruppen, allerdings war die durchschnittliche Konzentration in Hypophysenadenomen höher als in normalem Gewebe. Die Transfektion von primären Kulturen von GH (growth hormone) absondernder Hypophysenadenome mit dnTCF-4, welcher den Wnt/β-catenin Signalweg auf Transkriptionsebene blockiert, führte zu einer verminderten Zellproliferation. Weiterhin wurde in ACTH absondernden Hypophysenadenomen gezeigt, dass der Wnt/β-Catenin Signalweg im Vergleich zu normalem Hypophysengewebe hoch reguliert wurde. All diese Ergebnisse sprechen für die Hypothese, dass dieser Signalweg bei der Tumorbildung von Hypophysenadenomen beteiligt ist. CRH fördert physiologisch verschiedene Zellfunktionen, während SRIF diese in gleichem Maße physiologisch hemmt. Beide üben ihre jeweiligen Effekte durch Aktivierung und Hemmung der cAMP Bildung aus. In dieser Arbeit wurden deshalb sowohl der fördernde Effekt von CRH als auch der hemmende Effekt von SRIF auf den Wnt/β-catenin Signalweg von lactosomatotrophen GH3 Zellen aus Ratten untersucht. Weder CRH noch SRIF hatten Einfluss auf den Signalweg in der untersuchten Zelllinie. In corticotrophen Mäuse Hypophsenzellen (AtT-20 Zellen) CRH und Forskolin, welche die cAMP Bildung stimulieren, aktivierten auch den Wnt/β-catenin Signalweg. Beide Signalwege, cAMP/PKA und Wnt/β-catenin, haben eine gemeinsame „Schnittstelle“ im Protein GSK-3β, welches durch Forskolin an Ser9 schnell phosphoriliert und dadurch inaktiviert. Dies wiederum führt zu einer verminderten Phosphorilierung von β-Catenin. Im Gegensatz dazu verursachte SRIF, das die cAMP-Bildung hemmt, eine geringere Signalübertragung durch den Wnt/β-catenin Signalweg sowohl im Grundzustand als auch nach Forskolin-Stimulation durch eine Verminderung der Phosphorylierung von GSK-3β an Ser9. Eine Behandlung mit Forskolin erhöhte die Akkumulation von β-Catenin im Cytosol und im Kern wohingegen SRIF den gegenteiligen Effekt bewirkt. Diese Ergebnisse unterstützen die erhaltenen Daten für Cyclin D1: CRH fördert, SRIF hemmt die Menge dieses Proteins. CRH und Forskolin erhöhen die Proliferation von AtT-20 Zellen wohingegen SRIF diese vermindert. Dies könnte von ihrem Einfluss auf die Wnt/β-Catenin/TCF-4 Kaskade herrühren, da CRH, Forskolin und SRIF ihr Zielgen Cyclin D1 modulieren. Cyclin D1 wiederum kontrolliert den Ablauf des Zellzyklus und der Zellproliferation. Die Transfektion mit dnTCF-4 reduzierte signifikant die Expression von Cyclin D1 auf mRNA- und Protein Ebene, ebenso wie die Proliferation von AtT-20 Zellen, was auf einen physiologischen Einfluss des β-Catenin/TCF-4 Komplexes auf die Kontrolle der corticotrophen Proliferation schließen läßt. Schlussfolgerung: Zusammenfassend zeigen diese Daten die wichtige Rolle des Wnt/β-Catenin Signalwegs für die Kontrolle der Proliferation von somatotrophen und corticotrophen Hypophysenzellen. Weiterhin wird in dieser Arbeit ein neuer molekularer Mechanismus für die Steuerung des Wnt/β-Catenin Signalwegs durch CRH und SRIF in AtT-20 Zellen beschrieben. In GH3 Zellen wurde keine Verbindung der beiden Signalwege festgestellt.Back ground and objectives: The Wnt signaling pathway is involved in the control of cellular proliferation and differentiation in various tissues including the endocrine system. Its role has been established in different tumors, too. Little, however, is known about this cascade in pituitary cells and their role in tumorigenesis. This study was aimed to investigate the status of Wnt/β-catenin pathway in pituitary adenomas and its regulation. Methods: In order to establish the status of Wnt/β-catenin pathway in pituitary adenomas, we investigated the expression of the key players in Wnt/β-catenin pathway, including β-catenin, TCF-4 and cyclin D1 in ACTH-secreting, GH-secreting and non-functioning pituitary adenomas. Effects of CRH and SRIF on the Wnt/β-catenin pathway were studied in AtT-20 cells and GH-3 cells. For analysis of mRNA expression, reverse transcriptase polymerized chain reaction (rtPCR) and for protein expression western blotting was performed. Moreover, for cellular localization of β-catenin immunocytochemistry and for β-catenin/TCF-4 complex formation analysis immunoprecipitation was performed. Cellular proliferation was measured by MTT proliferation assay. Results and observations: A heterogeneous expression of β-catenin, TCF-4 and cyclin D1 factors was present but overall the average concentration was higher in adenomas than in normal pituitary tissue. Transfection of primary cultures from GH-secreting pituitary adenomas with dnTCF-4, blocking the Wnt/β-catenin pathway at transcriptional level, reduced the cellular proliferation. Furthermore, upregulation of the Wnt/β-catenin pathway was demonstrated in ACTH-secreting pituitary adenomas as compared to normal pituitary tissue. All these findings are compatible with the hypothesis, that this pathway is involved in the tumorigenesis of GH-secreting, non-functioning and ACTH-secreting pituitary adenomas. Corticotrophin releasing hormone (CRH) is the physiological stimulator, and somatostatin (SRIF) is the physiological inhibitor of various cellular activities. Both exert their stimulatory and inhibitory effects, respectively, through activation and inhibition of cAMP formation. In this study I investigated the role of CRH on stimulation and SRIF on inhibition of the Wnt/β-catenin pathway in rat lactosomatotroph GH3 cells. No significant effects of CRH and SRIF on the pathway in this cell line were demonstrated. After this, the effect of CRH and SRIF on Wnt/β-catenin was investigated in mouse pituitary AtT-20 corticotroph cells. CRH and forskolin, which stimulate cAMP formation, stimulated the Wnt/β-catenin signaling pathway. Cross-signaling between the cAMP/PKA and the Wnt/β-catenin pathways occurred at GSK-3β, which was rapidly phosphorylated by forskolin at Ser9 thereby causing its inactivation and resulting in decreased phosphorylation of β-catenin. In contrast, SRIF which inhibits cAMP formation, caused attenuation of basal and forskolin stimulated Wnt/β-catenin signaling. This also involved GSK-3β since SRIF treatment reduced phosphorylation of GSK-3β at Ser9. Treatment with forskolin also increased whereas SRIF decreased the cytoplasmic and nuclear accumulation of β-catenin. These findings are compatible with the increase under CRH and decrease under SRIF treatment of cyclin D1. CRH and forskolin enhanced AtT-20 cell proliferation while it was reduced by SRIF. This might result from their action on the Wnt/β-catenin/TCF-4 cascade, since CRH, forskolin and SRIF modulated its target gene cyclin D1. Cyclin D1 controls cell cycle progression and proliferation. Transfection with dnTCF-4 significantly reduced both, cyclin D1 expression at mRNA and protein level as well as cellular proliferation of AtT-20 cells, suggesting a physiological role of β-catenin/TCF-4 complex for the control of corticotroph proliferation. Conclusion: These data demonstrate an important role of the Wnt/β-catenin signaling pathway in the proliferative control of pituitary somatotrophs and corticotrophs. Also in this study a novel molecular mechanism for the change of momentum of the Wnt/β-catenin pathway by CRH and SRIF in AtT-20 cells is described. In GH3 cells, no relation was found with regards to the two pathways

Phylogenetic association of Schizothorax plagiostomus with other schizothoracine fishes based on mitochondrial cytochrome B gene and control region

Cytochrome B (Cyt B) gene and control region of mitochondrial DNA are considered important for evaluating phylogenetic association of a species. In this study, we sequenced Cyt B and control region of Schizothorax plagiostomus and constructed phylogenetic association tree of S. plagiostomus with 23 schizothoracine fishes. We found S. plagiostomus to be closely associated with S. labiatus, S. richardsonii, S. progastus, and S. esocinus, with high-bootstraps values. Several conserved sequence blocks were identified within D-loop sequences. These are highly conserved within genus Schizothorax compared to other. This study reports the phylogenetic position of the S. plagiostomus among schizothoracines fishes and organization of D-loop region in S. plagiostomus from Pakistan

Prevalence of sputum smear positive pulmonary tuberculosis at Dargai, District Malakand, Pakistan: A four year retrospective study

Tuberculosis (TB) is an ancient disease however, poses serious challenge in the modern era in developing as well as developed countries. Every year millions of peoples are infected with TB and millions of peoples lose their lives. This study was undertaken to determine the prevalence of pulmonary tuberculosis sputum smear positive (PTB-SS+ve) among the suspected TB patients at Tehsil Head Quarter (THQ) Hospital Dargai, District Malakand Khyber Pakhtunkhwa, Pakistan. A retrospective study was designed from January 2011 to December 2014. Out of 736 registered and suspected patients of TB, (40.08%) were PTB-SS+ve, (15.63%) were PTB-SS−ve whereas the remaining cases were diagnosed with extra-pulmonary TB, hence excluded from the study. The ratio of PTB-SS+ve cases was higher in females (57.63%) compared to males (42.37%). Furthermore, in the age group 60 years age group PTB-SS+ve cases were (9.83%). No difference was found in the years 2013 and 2014 regarding PTB-SS+ve cases registration. PTB still presents a serious health issue in the region and rapid prophylactic measures are needed to eradicate the issue

U-Shaped Low-Complexity Type-2 Fuzzy LSTM Neural Network for Speech Enhancement

Speech enhancement (SE) aims to improve the intelligibility and perceptual quality of speech contaminated by noise signals through spectral or temporal changes. Deep learning models achieve speech enhancement and estimate the magnitude spectrum. This paper proposes a novel and computationally efficient deep learning model to enhance noisy speech. The model pre-processes the noisy speech magnitude by redistributing energy from high-energy voiced segments to low-energy unvoiced segments using an adaptive power law transformation while maintaining the total energy of the speech signals constant. A U-shaped fuzzy long short-term memory (UFLSTM) estimates the magnitude of a time-frequency (T-F) mask by using the pre-processed data. Residual connections to the similar-shaped layers are added to avoid gradient decay. Attention process is adopted by modifying the forget gate of UFLSTM. To make a causal speech enhancement system, the processing does not include any future audio frames. We compare the proposed speech enhancement to other deep learning models in different noisy environments with signal-to-noise ratios of 0 dB, 5 dB, and 10 dB. The experiments show that the proposed SE system outscores the competing deep learning models and considerably improves speech intelligibility and quality. In terms of STOI and PESQ, the LibriSpeech database improves results by (0.211) 21.1% and (0.95) 36.39%, respectively, over noisy speech in seen noisy conditions, and by (0.199) 19.9% and (0.94) 35.69% over noisy speech in unseen noisy conditions. Further, the cross-corpus analysis shows that proposed SE system performs better when trained with the DNS dataset as compared to the LibriSpeech, VoiceBank, and TIMIT datasets