Challenges and prospects in the public health research system in the occupied Palestinian territory: a qualitative study

Background

A public health research system is the bedrock of health systems to improve population health, system responsiveness, and equity. An international concern, referred to as the 10/90 gap, is that less than 10% of global funds are devoted to diseases or conditions that account for 90% of the global disease burden, particularly in developing countries. Palestinian health research is progressing, but it is not sufficiently investigated, with a remarkable knowledge gap on its conceptualisation, stewardship, stakeholders, and capacity and resources. The aim of this study was to understand the Palestinian public health research system by investigating challenges related to the system components that need to be strengthened.

Substrate for endothelial prostacyclin production in the presence of platelets exposed to collagen is derived from the platelets rather than the endothelium

Interactions between vascular endothelial cells and blood platelets have been investigated using a model microcirculation consisting of microcarrier beads colonized with human umbilical vein endothelial cells (HUVECs) and perfused with washed platelet suspensions. To simulate the effects of endothelial desquamation and exposure of subendothelium, fibrillar collagen in suspension was coinjected with the platelets. In this model, neither the passage of platelets alone nor collagen alone stimulated prostacyclin (PGI2) production by the HUVECs. Platelets activated by coinjection with collagen released thromboxane A2 (TXA2), and this was associated with the simultaneous production of PGI2 by the HUVECs. By means of double-isotope experiments with [3H]arachidonic acid (AA) incorporated into platelets and [14C]-AA into HUVECs, it was shown that all the PGI2 generated was derived from platelet AA and/or endoperoxides. This interpretation was strengthened by the finding that PGI2 production was not prevented by treatment of HUVECs with indomethacin followed by perfusion with collagen-stimulated platelets. AA metabolites in double-isotope label experiments were further characterized by reverse-phase chromatography, and it was shown that both cyclooxygenase and lipoxygenase products of the HUVECs were derived from platelet membrane lipid. Thrombin regularly produced transient PGI2 release, but showed rapid tachyphylaxis. Platelet-derived compounds including ADP, ATP, and platelet-activating factor (PAF) did not produce PGI2 release by HUVECs in this system. Thus, the transfer of AA and metabolites from collagen- stimulated platelets is likely to be the mechanism for PGI2 production in the context of minor degrees of endothelial desquamation.     

Parental origin of mutation and the risk of breast cancer in a prospective study of women with a BRCA1 or BRCA2 mutation

The objective is to estimate the risk of breast cancer in women who carry a deleterious BRCA1 or BRCA2 mutation, according to parental origin of mutation. We conducted a cohort study of women with a BRCA1 mutation (n = 1523) or BRCA2 mutation (n = 369) who had not been diagnosed with breast or ovarian cancer. For each woman, the pedigree was reviewed and the origin of the mutation was assigned as probable paternal or maternal. The hazard ratio (HR) for developing breast cancer in the follow‐up period was estimated for women with a paternal mutation compared to a maternal mutation. The risk of breast cancer was modestly higher in women with a paternal BRCA1 mutation compared to women with a maternal BRCA1 mutation (HR = 1.46; 95% CI = 0.99–2.16) but the difference was not significant (p = 0.06). The parental mutation origin did not affect the risk in women with a BRCA2 mutation. Our results are consistent with the hypothesis that there is an increased risk of breast cancer among women with a paternally inherited BRCA1 mutation compared to a maternally inherited mutation. However, the data are not sufficiently compelling to justify different screening recommendations for the two subgroups.     

To tell or not to tell – what to do about p.C282Y heterozygotes identified by HFE screening

Hereditary hemochromatosis (HH) is a common preventable disorder of iron overload that can result in liver cirrhosis and reduced lifespan. Most HH is due to homozygosity for the HFE p.C282Y substitution. We conducted a study of screening for p.C282Y in high schools where p.C282Y heterozygotes (CY) individuals were informed of their genotype by letter. We studied whether these individuals understood the implications of their genotype, whether this resulted in anxiety or reduced health perception and whether cascade testing was higher in families of CY than wild‐type homozygous (CC) individuals. We found 586 of 5757 (1 in 10) screened individuals were CY. One month after receiving their result, 83% correctly answered that they have one copy of p.C282Y. There was no adverse change in anxiety or health perception from prior to screening to 1 month after receiving results. Significantly more family members of CY individuals than CC individuals were informed about HH and had testing for HH. In conclusion, we found that informing CY individuals of their genotype does not increase anxiety and the implications are generally well understood. This leads to cascade testing in a minority of families. CY individuals should be informed of their genetic status when identified by population screening.     

Marine natural products from sponges (Porifera) of the order Dictyoceratida (2013 to 2019); a promising source for drug discovery

Marine organisms have been considered an interesting target for the discovery of different classes of secondary natural products with wide-ranging biological activities. Sponges which belong to the order Dictyoceratida are distinctly classified into 5 families: Dysideidae, Irciniidae, Spongiidae, Thorectidae, and Verticilliitidae. In this review, compounds isolated from Dictyoceratida sponges were discussed with their biological potential within the period 2013 to December 2019. Moreover, analysis of the physicochemical properties of these marine natural products was investigated and the results showed that 78% of the compounds have oral bioavailability potential. This review highlights sponges of the order Dictyoceratida as exciting source for discovery of new drug leads.

Marine organisms have been considered an interesting target for the discovery of different classes of secondary natural products with wide-ranging biological activities.     

基于UPLC-Q-TOF-MS对蒙药苏格木勒-3水提物化学成分的研究

目的：对蒙药苏格木勒-3水提物进行化学成分研究,构建较为全面的化学成分谱,为苏格木勒-3水提物有效物质基础研究奠定基础。方法：采用超高液相色谱串联四级杆飞行时间质谱（UPLC-Q-TOF-MS）技术,使用ESI离子源,通过mzCloud与mzVoult软件以及质谱裂解规律,并结合对照品及相关文献资料比对进行定性分析。结果：经过分析,从蒙药苏格木勒-3水提物中共鉴定出42个成分,主要包括氨基酸、酚酸类、黄酮类、内酯类、生物碱类及其他类等6类成分,并对各成分的药材来源进行归属。结论：本研究全面、快速、准确地分析了蒙药苏格木勒-3水提物的化学成分,为其药效物质基础和质量控制等研究奠定了基础。     

Molecular signalling of a novel curcumin derivative versus Tadalafil in erectile dysfunction

The efficacy of a novel curcumin derivative (NCD) versus tadalafil in erectile signalling was assessed. Ten control male rats and 50 diabetic male rats were used and divided into the following: diabetic (DM), curcumin (CURC), NCD, tadalafil and NCD combined with tadalafil rat groups. Cavernous tissue gene expression of heme oxygenase‐1 (HO‐1), Nrf2, NF‐B and p38, enzyme activities of heme oxygenase (HO) and nitric oxide synthase (NOS), cGMP and intracavernosal pressure (ICP)/mean arterial pressure (MAP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction (ED) was confirmed by the significant decrease in ICP/MAP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO‐1 gene and a significant increase in NF‐?β, p38 genes. Administration of all therapeutic interventions led to a significant increase in ICP/MAP, cGMP levels, a significant increase in HO‐1 and NOS enzymes, a significant increase in HO‐1, and Nrf2 gene expression, and a significant decrease in NF‐?β, p38 gene expression. NCD or its combination with tadalafil showed significant superiority and more prolonged duration of action. In conclusion, a tendency was observed that CURC and NCD have high efficacy and more prolonged duration of action in enhancing erectile function.