TRANSITIONAL CARE INITIATIVE WITHIN MENTAL HEALTH SERVICES IN QATAR: DESCRIPTION AND EVALUATION OF AN INNOVATIVE CARE MODEL

The importance of effective health care transitioning of young people from adolescent to adult health services is well established in general and within mental health services in particular. There is no previous literature focusing on the implementation of the transitional care model within mental health services in the Arabian Gulf region. We outline details of how the international best practice of effective transitioning of young people from Child and Adolescent to Adult mental health services was adopted and implemented in the State of Qatar. The impact of this crucial initiative on patient care and service delivery is also explained

A New Solution to the Plasma Starved Event Horizon Magnetosphere: Application to the Forked Jet in M87

Very Long Baseline Interferometry observations at 86 GHz reveal an almost hollow jet in M87 with a forked morphology. The detailed analysis presented here indicates that the spectral luminosity of the central spine of the jet in M87 is a few percent of that of the surrounding hollow jet $200 -400 \mu\rm{as}$ from the central black hole. Furthermore, recent jet models in indicate that a hollow "tubular" jet can explain a wide range of plausible broadband spectra originating from jetted plasma located within $\sim 30\mu\rm{as}$ of the central black hole, including the 230 GHz correlated flux detected by the Event Horizon Telescope. Most importantly, these hollow jets from the inner accretion flow have an intrinsic power capable of energizing the global jet out to kiloparsec scales. Thus motivated, this paper considers new models of the event horizon magnetosphere (EHM) in low luminosity accretion systems. Contrary to some models, the spine is not an invisible powerful jet. It is an intrinsically weak jet. In the new EHM solution, the accreted poloidal magnetic flux is weak and the background photon field is weak. It is shown how this accretion scenario naturally results in the dissipation of the accreted poloidal magnetic flux in the EHM not the accumulation of poloidal flux required for a powerful jet. The new solution indicates less large scale poloidal magnetic flux (and jet power) in the EHM than in the surrounding accretion flow and cannot support significant EHM driven jets.Comment: To appear in Astronomy and Astrophysics. Revision fixes typos found during proof

Excellency of Hydroxyapatite Composite Scaffolds for Bone Tissue Engineering

The hydroxyapatite [HAp, Ca10(PO4)6(OH)2] has a variety of applications in bone fillers and replacements due to its excellent bioactivity and osteoconductivity. It comprises the main inorganic component of hard tissues. Among the various approaches, a composite approach using several components like biopolymer, gelatin, collagen, and chitosan in the functionalization of scaffolds with HAp has the prospective to be an engineered biomaterial for bone tissue engineering. HAp composite scaffolds have been developed to obtain a material with different functionalities such as surface reactivity, bioactivity, mechanical strength, and capability of drug or growth factor delivery. Several techniques and processes for the synthesis and fabrication of biocompatible HAp composite scaffolds suitable for bone regeneration are addressed here. Further, this chapter described the excellences of various HAp composite scaffolds used in in vitro and in vivo experiments in bone tissue engineering

Association between Diabetes Consequences and Quality of Life among Patients with Diabetes Mellitus in the Aseer Province of Saudi Arabia

BACKGROUND: Diabetes mellitus (DM) is a major health-care burden worldwide. AIM: The aim of the study was to explore how the quality of life (QoL) of DM patients could be affected in the Aseer Province of the Kingdom of Saudi Arabia (KSA). METHODS: A cross-sectional, multicenter study in DM patients of both sexes and all age groups in Aseer Province were done using a validated self-administered questionnaire. The study was conducted between April 1, 2018 and November 25, 2018. RESULTS: A total of 418 patients completed our questionnaire, of which 240 (58%) were male and 178 (42%) were female. Furthermore, 50.23% were married and 104 (24.16%) were illiterate. We found that 403 (96.42%) respondents had type-2 DM and 315 (75.35%) had a family history of DM. In addition, 132 (31.57%) respondents were on monotherapy whereas only 61 (14.59%) were using combination therapy. Hypertension was the most prevalent comorbidity (166, 39.71%) and peripheral neuropathy the most prevalent complication of DM (157, 37.56%). CONCLUSION: DM had a significant impact on QoL among patients from Aseer Province in KSA. Our study underscores the importance of generating data on QoL among DM patients

Assessing Molecular Signature for Some Potential Date (Phoenix dactylifera L.) Cultivars from Saudi Arabia, Based on Chloroplast DNA Sequences rpoB and psbA-trnH

Phoenix dactylifera L. (date palm), being economically very important, is widely cultivated in the Middle East and North Africa, having about 400 different cultivars. Assessment of date cultivars under trading and farming is a widely accepted problem owing to lack of a unique molecular signature for specific date cultivars. In the present study, eight different cultivars of dates viz., Khodry, Khalas, Ruthana, Sukkari, Sefri, Segae, Ajwa and Hilali were sequenced for rpoB and psbA-trnH genes and analyzed using bioinformatics tools to establish a cultivar-specific molecular signature. The combined aligned data matrix was of 1147 characters, of which invariable and variable sites were found to be 958 and 173, respectively. The analysis clearly reveals three major groups of these cultivars: (i) Khodary, Sefri, Ajwa, Ruthana and Hilali (58% BS); (ii) Sukkari and Khalas (64% BS); and (iii) Segae. The economically most important cultivar Ajwa showed similarity with Khodary and Sefri (67% BS).The sequences of the date cultivars generated in the present study showed bootstrap values between 38% and 70% so these sequences could be carefully used as molecular signature for potential date cultivars under trading and selection of genuine cultivars at the seedling stage for farming

IFPA meeting 2018 workshop report II: Abnormally invasive placenta; inflammation and infection; preeclampsia; gestational trophoblastic disease and drug delivery

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2018 there were nine themed workshops, five of which are summarised in this report. These workshops discussed new perspectives and knowledge in the following areas of research: 1) preeclampsia; 2) abnormally invasive placenta; 3) placental infection; 4) gestational trophoblastic disease; 4) drug delivery to treat placental dysfunction

Circulating exosomal immuno-oncological checkpoints and cytokines are potential biomarkers to monitor tumor response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients

Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes of NSCLC patients with better overall survival. However, 15-40% of the patients still fail to respond to ICIs therapy. Identification of biomarkers associated with responses are mandated in order to increase the efficacy of such therapy. In this study we evaluated 27 serum-derived exosomal immuno-oncological proteins and 44 cytokines/chemokines before and after ICIs therapy in 17 NSCLC patients to identify surrogate biomarkers for treatment/monitoring patient stratification for maximum therapeutic benefit. We first confirmed the identity of the isolated exosomes to have their specific markers (CD63, CD81, HSP70 and CD91). We have demonstrated that baseline concentration of exosomal-PD-L1 (p<0.0001), exosomal-PD-L2 (p=0.0413) and exosomal-PD-1 (p=0.0131) from NSCLC patients were significantly higher than their soluble-free forms. Furthermore, the exosomal-PD-L1 was present in all the patients (100%), while only 71% of patients expressed tissue PD-L1. This indicates that exosomal-PD-L1 is a more reliable diagnostic biomarker. Interestingly, exosomal-PD-L2 expression was significantly higher (p=0.0193) in tissue PD-L1-negative patients compared to tissue PD-L1-positive patients. We have also shown that immuno-oncological proteins isolated from pre-ICIs treated patients were significantly higher in exosomes compared to their soluble-free counterparts (CD152, p=0.0008; CD80, p=0.0182; IDO, p=0.0443; Arginase, p<0.0001; Nectin-2, p<0.0001; NT5E, p<0.0001; Siglec-7, p<0.0001; Siglec-9, p=0.0335; CD28, p=0.0092; GITR, p<0.0001; MICA, p<0.0001). Finally, the changes in the expression levels of exosomal immuno-oncological proteins/cytokines and their correlation with tumor response to ICIs treatment were assessed. There was a significant downregulation of exosomal PD-L1 (p=0.0156), E-Cadherin (p=0.0312), ULBP1 (p=0.0156), ULBP3 (p=0.0391), MICA (p=0.0391), MICB (p=0.0469), Siglec7 (p=0.0078) and significant upregulation of exosomal PD-1 (p=0.0156) and IFN- γ (p=0.0156) in responding patients. Non-responding patients showed a significant increase in exosomal-PD-L1 (p=0.0078). Furthermore, responding-patients without liver-metastasis showed significant-upregulation of PD-1 (p=0.0070), and downregulation of ULBP1 (p=0.0137) and Siglec-7 (p=0.0037). Non-responding patients had significant-downregulation of ULBP3 (p=0.0317) in patient without brain-metastasis and significant-upregulation/downregulation of PD-L1 and ULBP3 (p=0.0262/0.0286) in patients with pulmonary-metastasis. We demonstrated for the first time that exosomal immuno-oncological proteins/cytokines are potential biomarkers to monitor response to ICIs therapy and can predict the clinical outcomes in NSCLC patients.This research was funded by Academic Health System, Medical Research Center, Hamad Medical Corporation, Doha, Qatar, grant number MRC-01-20-507 and the Article Processing Charges was funded by Academic Health System, Medical Research Center, Hamad Medical Corporation, Doha, Qatar

Circulating exosomal immuno-oncological checkpoints and cytokines are potential biomarkers to monitor tumor response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients

Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes of NSCLC patients with better overall survival. However, 15-40% of the patients still fail to respond to ICIs therapy. Identification of biomarkers associated with responses are mandated in order to increase the efficacy of such therapy. In this study we evaluated 27 serum-derived exosomal immuno-oncological proteins and 44 cytokines/chemokines before and after ICIs therapy in 17 NSCLC patients to identify surrogate biomarkers for treatment/monitoring patient stratification for maximum therapeutic benefit. We first confirmed the identity of the isolated exosomes to have their specific markers (CD63, CD81, HSP70 and CD91). We have demonstrated that baseline concentration of exosomal-PD-L1 (p&lt;0.0001), exosomal-PD-L2 (p=0.0413) and exosomal-PD-1 (p=0.0131) from NSCLC patients were significantly higher than their soluble-free forms. Furthermore, the exosomal-PD-L1 was present in all the patients (100%), while only 71% of patients expressed tissue PD-L1. This indicates that exosomal-PD-L1 is a more reliable diagnostic biomarker. Interestingly, exosomal-PD-L2 expression was significantly higher (p=0.0193) in tissue PD-L1-negative patients compared to tissue PD-L1-positive patients. We have also shown that immuno-oncological proteins isolated from pre-ICIs treated patients were significantly higher in exosomes compared to their soluble-free counterparts (CD152, p=0.0008; CD80, p=0.0182; IDO, p=0.0443; Arginase, p&lt;0.0001; Nectin-2, p&lt;0.0001; NT5E, p&lt;0.0001; Siglec-7, p&lt;0.0001; Siglec-9, p=0.0335; CD28, p=0.0092; GITR, p&lt;0.0001; MICA, p&lt;0.0001). Finally, the changes in the expression levels of exosomal immuno-oncological proteins/cytokines and their correlation with tumor response to ICIs treatment were assessed. There was a significant downregulation of exosomal PD-L1 (p=0.0156), E-Cadherin (p=0.0312), ULBP1 (p=0.0156), ULBP3 (p=0.0391), MICA (p=0.0391), MICB (p=0.0469), Siglec7 (p=0.0078) and significant upregulation of exosomal PD-1 (p=0.0156) and IFN- γ (p=0.0156) in responding patients. Non-responding patients showed a significant increase in exosomal-PD-L1 (p=0.0078). Furthermore, responding-patients without liver-metastasis showed significant-upregulation of PD-1 (p=0.0070), and downregulation of ULBP1 (p=0.0137) and Siglec-7 (p=0.0037). Non-responding patients had significant-downregulation of ULBP3 (p=0.0317) in patient without brain-metastasis and significant-upregulation/downregulation of PD-L1 and ULBP3 (p=0.0262/0.0286) in patients with pulmonary-metastasis. We demonstrated for the first time that exosomal immuno-oncological proteins/cytokines are potential biomarkers to monitor response to ICIs therapy and can predict the clinical outcomes in NSCLC patients

Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration

Background: Colorectal cancer (CRC) is the 3rd most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown. Methods: 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29. Results: Many anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and −6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c release and PARP cleavage. The results further demonstrate that 3c inhibits cell migration by modulating EMT markers and inhibiting TGFβ-induced phosphorylation of Smad2 and Samd3. Conclusions: Our findings thus demonstrate that 3c disrupts redox balance in colorectal cancer cells and support the notion that this agent may be effective for the treatment of colorectal cancer