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BackgroundBased on findings from other contexts, informed by intergroup contact theory, that more contact is associated with less stigma, we hypothesized that community members with greater exposure to cases of Ebola virus disease (EVD) were less likely to report EVD-related stigma towards EVD survivors. We assessed personal stigmatizing attitudes towards Ebola survivors, which reflects personal fear and judgement, as well as perceived stigma towards EVD survivors, which reflects an individual's perception of the attitudes of the community towards a stigmatized group.MethodsFrom September 2016 to July 2017, we conducted a cross-sectional, community-based study of EVD-related stigma among individuals who did not contract Ebola in four EVD-affected rural communities of Kono District, Sierra Leone. We identified individuals from all quarantined households and obtained a random sample of those who were unexposed. Exposed individuals either lived in a quarantined household or were reported to have been in contact with an EVD case. Our explanatory variable was proximity to an EVD case during the outbreak. Our primary outcome was stigma towards EVD survivors, measured by a 6-item adapted HIV-related stigma index validated in Zambia and South Africa, with 1 item reflecting personal stigmatizing attitudes and 5 items reflecting perceived community stigma. The 6-item EVD stigma index had good internal consistency (Cronbach's alpha=0.82). We used modified Poisson and negative binomial regression models, adjusting for potential confounders, to estimate the association between exposure proximity and EVD stigma.ResultsWe interviewed 538 participants aged 12 to 85 years. Most (57%) had been quarantined. Over one-third (39%) reported personal stigmatizing attitudes or perceived community stigma; the most frequently endorsed item was fear and judgment towards EVD survivors. Having contact with someone with EVD was significantly associated with a lower likelihood of perceived community stigma (prevalence ratio [PR], 0.26; 95% CI, 0.13-0.54) and personal stigmatizing attitudes (PR, 0.44; 95% CI, 0.29-0.65). In contrast, being quarantined was significantly associated with a higher likelihood of perceived community stigma (PR, 3.9; 95% CI, 1.5-10.1).ConclusionsIn this cross-sectional study, we found evidence of an inverse relationship between EVD-related stigma and contact with an EVD case. This finding substantiates intergroup contact theory and may form the basis for anti-stigma interventions.

BackgroundTransmission by unreported cases has been proposed as a reason for the 2013-2016 Ebola virus (EBOV) epidemic decline in West Africa, but studies that test this hypothesis are lacking. We examined a transmission chain within social networks in Sukudu village to assess spread and transmission burnout.MethodsNetwork data were collected in 2 phases: (1) serological and contact information from Ebola cases (n = 48, including unreported); and (2) interviews (n = 148), including Ebola survivors (n = 13), to identify key social interactions. Social links to the transmission chain were used to calculate cumulative incidence proportion as the number of EBOV-infected people in the network divided by total network size.ResultsThe sample included 148 participants and 1522 contacts, comprising 10 social networks: 3 had strong links (>50% of cases) to the transmission chain: household sharing (largely kinship), leisure time, and talking about important things (both largely non-kin). Overall cumulative incidence for these networks was 37 of 311 (12%). Unreported cases did not have higher network centrality than reported cases.ConclusionsAlthough this study did not find evidence that explained epidemic decline in Sukudu, it excluded potential reasons (eg, unreported cases, herd immunity) and identified 3 social interactions in EBOV transmission.

BackgroundIt remains unclear if there is a dose-dependent relationship between exposure risk to Ebola virus (EBOV) and severity of illness.MethodsFrom September 2016 to July 2017, we conducted a cross-sectional, community-based study of Ebola virus disease (EVD) cases and household contacts of several transmission chains in Kono District, Sierra Leone. We analyzed 154 quarantined households, comprising both reported EVD cases and their close contacts. We used epidemiological surveys and blood samples to define severity of illness as no infection, pauci-/asymptomatic infection, unrecognized EVD, reported EVD cases who survived, or reported EVD decedents. We determine seropositivity with the Filovirus Animal Nonclinical Group EBOV glycoprotein immunoglobulin G antibody test. We defined levels of exposure risk from 8 questions and considered contact with body fluid as maximum exposure risk.ResultsOur analysis included 76 reported EVD cases (both decedents and survivors) and 421 close contacts. Among these contacts, 40 were seropositive (22 paucisymptomatic and 18 unrecognized EVD), accounting for 34% of the total 116 EBOV infections. Higher exposure risks were associated with having had EBOV infection (maximum risk: adjusted odds ratio [AOR], 12.1 [95% confidence interval {CI}, 5.8-25.4; trend test: P

Objectives: World Health Organization issued Joint Statement on Data Protection and Privacy in the COVID-19 Response stating that collection of vast amounts of personal data may potentially lead to the infringement of fundamental human rights and freedoms. The Organization for Economic Cooperation and Development called on national governments to adhere to the international principles for data security and confidentiality. This paper describes the methods used to assist the Ministry of Health in bringing awareness of the data ownership, confidentiality and security principles to COVID-19 responders. Methods: The Sierra Leone Epidemiological Data (SLED) Team data managers conducted training for groups of COVID-19 responders. Training included presentations on data confidentiality, information disclosure, physical and electronic data security, and cyber-security; and interactive discussion of real-life scenarios. A game of Jeopardy was created to test the participant's knowledge. Results: This paper describes the methods used by the SLED Team to bring awareness of the DOCS principles to more than 2,500 COVID-19 responders. Conclusion: Similar efforts may benefit other countries where the knowledge, resources, and governing rules for protection of personal data are limited. [ABSTRACT FROM AUTHOR]

Studies have shown that people suffering from food insecurity are at higher risk for infectious and noncommunicable diseases and have poorer health outcomes. No study, however, has examined the association between food insecurity and outcomes related to Ebola virus disease (EVD). We conducted a cross-sectional study in two Ebola-affected communities in Kono district, Sierra Leone, from November 2015 to September 2016. We enrolled persons who were determined to have been exposed to Ebola virus. We assessed the association of food insecurity, using an adapted version of the Household Food Insecurity Access Scale, a nine-item scale well validated across Africa, with having been diagnosed with EVD and having died of EVD, using logistic regression models with cluster-adjusted standard errors. We interviewed 326 persons who were exposed to Ebola virus; 61 (19%) were diagnosed with EVD and 45/61 (74%) died. We found high levels (87%) of food insecurity, but there was no association between food insecurity and having been diagnosed with EVD. Among EVD cases, those who were food insecure had 18.3 times the adjusted odds of death than those who were food secure (P = 0.03). This is the first study to demonstrate a potential relationship between food insecurity and having died of EVD, although larger prospective studies are needed to confirm these findings.

Wheat, a staple cereal crop, faces challenges due to climate change and increasing global population. Maintaining genetic diversity is vital for developing drought-tolerant cultivars. This study evaluated the genetic diversity and drought response of five wheat cultivars and their corresponding F1 hybrids under well-watered and drought stress conditions. Molecular profiling using ISSR and SCoT-PCR markers revealed 28 polymorphic loci out of 76 amplified. A statistically significant impact of parental genotypes and their crosses was observed on all investigated agro-morphological traits, including root length, root weight, shoot length, shoot weight, proline content, spikelet number/spike, spike length, grain number/spike, and grain weight/spike. The parental genotypes P1 and P3 had desirable positive and significant general combining ability (GCA) effects for shoot fresh weight, shoot dry weight, root fresh weight, root dry weight, shoot length, and root length under well-watered conditions, while P3 and P5 recorded the highest GCA estimates under drought stress. P3 and P4 showed the highest GCA effects for number of spikelets per spike, the number of grains per spike, and grain weight per spike under normal conditions. P5 presented the maximum GCA effects and proved to be the best combiner under drought stress conditions. The cross P1× P3 showed the highest positive specific combining ability (SCA) effects for shoot fresh weight under normal conditions, while P2×P3 excelled under water deficit conditions. P1× P2, P1 × P3, and P4× P5 were most effective for shoot dry weight under normal conditions, whereas P1×P3 and P3×P5 showed significant SCA effects under drought stress. Positive SCA effects for root fresh weight and shoot length were observed for P3×P5 under stressed conditions. Additionally, P4×P5 consistently recorded the highest SCA for root length in both environments, and P3×P5 excelled in the number of spikelets, grains per spike, and grain weight per spike under drought conditions. The evaluated genotypes were categorized based on their agronomic performance under drought stress into distinct groups ranging from drought-tolerant genotypes (group A) to drought-sensitive ones (group C). The genotypes P5, P2×P5, and P3×P5 were identified as promising genotypes to improve agronomic performance under water deficit conditions. The results demonstrated genetic variations for drought tolerance and highlighted the potential of ISSR and SCoT markers in wheat breeding programs for developing drought-tolerant cultivars. [ABSTRACT FROM AUTHOR]

Introduction: The development of a new type of Thymidylate synthase (TS) inhibitor that could inhibit cancer cells' proliferation and anti-angiogenesis is of great significance for cancer's clinical treatment. Objectives: Our research hopes to develop a TS inhibitor that is more effective than the current first-line clinical treatment of pemetrexed (PTX) and provide a new reference for the clinical treatment of non-small cell lung cancer (NSCLC). Methods: We obtained a series of novel TS inhibitors by chemical synthesis. Moreover, TS assay and molecular docking to verify the target compound's inhibitory mode. Use MTT assay, colony-forming assay, flow cytometry, and western blot to verify the compound's inhibitory effect on cancer cell proliferation and its mechanism; and explore the compound’s effect on angiogenesis in vitro and in vivo. Further, explore the hit compound's anti-cancer ability through the xenograft tumor model and the orthotopic cancer murine model. Results: A series of N-(3-(5-phenyl-1,3,4-oxadiazole-2-yl) phenyl)-2,4-dihydroxypyrimidine-5-sulfamide derivatives were synthesized as TS inhibitors for the first time. All target compounds significantly inhibited hTS enzyme activity and demonstrated significant antitumor activity against five cancer cell lines. Notably, 7f had a high selectivity index (SI) and unique inhibitory effects on eight NSCLC cells. In-depth research indicated that 7f could induce apoptosis by the mitochondrial pathway in A549 and PC-9 cells through the upregulation of wild-type P53 protein expression. Additionally, 7f was shown to inhibit angiogenesis in vitro and in vivo. In vivo studies, compared to PTX, 7f significantly inhibited tumor growth in A549 cell xenografts and had a higher therapeutic index (TGI). Moreover, 7f could prolong the survival of the orthotopic lung cancer murine model more effectively than PTX. Conclusion: The anti-angiogenic effect of 7f provides a new reference for the development of TS inhibitors and the clinical treatment of NSCLC.

Nitrogen is an essential element for maize growth, but excessive application can lead to various environmental and ecological issues, including water pollution, air pollution, greenhouse gas emissions, and biodiversity loss. Hence, developing maize hybrids resilient to low-N conditions is vital for sustainable agriculture, particularly in nitrogen-deficient soils. Combining ability and genetic relationships among parental lines is crucial for breeding superior hybrids under diverse nitrogen levels. This study aimed to assess the genetic diversity of maize inbred lines using simple sequence repeat (SSR) markers and evaluate their combining ability to identify superior hybrids under low-N and recommended conditions. Local and exotic inbred lines were genotyped using SSR markers, revealing substantial genetic variation with high gene diversity (He = 0.60), moderate polymorphism information content (PIC = 0.54), and an average of 3.64 alleles per locus. Twenty-one F1 hybrids were generated through a diallel mating design using these diverse lines. These hybrids and a high yielding commercial check (SC-131) were field-tested under low-N and recommended N conditions. Significant variations (p < 0.01) were observed among nitrogen levels, hybrids, and their interaction for all recorded traits. Additive genetic variances predominated over non-additive genetic variances for grain yield and most traits. Inbred IL3 emerged as an effective combiner for developing early maturing genotypes with lower ear placement. Additionally, inbreds IL1, IL2, and IL3 showed promise as superior combiners for enhancing grain yield and related traits under both low-N and recommended conditions. Notably, hybrids IL1×IL4, IL2×IL5, IL2×IL6, and IL5×IL7 exhibited specific combining abilities for increasing grain yield and associated traits under low-N stress conditions. Furthermore, strong positive associations were identified between grain yield and specific traits like plant height, ear length, number of rows per ear, and number of kernels per row. Due to their straightforward measurability, these relationships underscore the potential of using these traits as proxies for indirect selection in early breeding generations, particularly under low-N stress. This research contributes to breeding nitrogen-efficient maize hybrids and advances our understanding of the genetic foundations for tolerance to nitrogen limitations. [ABSTRACT FROM AUTHOR]

Water deficit poses significant environmental stress that adversely affects the growth and productivity of durum wheat. Moreover, projections of climate change suggest an increase in the frequency and severity of droughts, particularly in arid regions. Consequently, there is an urgent need to develop drought-tolerant and high-yielding genotypes to ensure sustained production and global food security in response to population growth. This study aimed to explore the genetic diversity among local and exotic durum wheat genotypes using simple sequence repeat (SSR) markers and, additionally, to explore the combining ability and agronomic performance of assessed durum wheat genotypes and their 28 F1 crosses under normal and drought stress conditions. The investigated SSRs highlighted and confirmed the high genetic variation among the evaluated parental durum wheat genotypes. These diverse eight parental genotypes were consequently used to develop 28 F1s through a diallel mating design. The parental durum genotypes and their developed 28 F1s were assessed under normal and drought stress conditions. The evaluated genotypes were analyzed for their general and specific combining abilities as well as heterosis for agronomic traits under both conditions. The local cultivar Bani-Suef-7 (P8) is maintained as an effective combiner for developing shortened genotypes and improving earliness. Moreover, the local cultivars Bani-Suef-5 (P7) and Bani-Suef-7 (P8) along with the exotic line W1520 (P6) demonstrated excellent general combining ability for improving grain yield and its components under drought stress conditions. Furthermore, valuable specific hybrid combinations, W988 × W994 (P1 × P2), W996 × W1518 (P3 × P5), W1011 × W1520 (P4 × P6), and Bani-Suef-5 × Bani-Suef-7 (P7 × P8), were identified for grain yield and its components under drought stress conditions. The assessed 36 genotypes were grouped according to tolerance indices into five clusters varying from highly drought-sensitive genotypes (group E) to highly drought-tolerant (group A). The genotypes in cluster A (two crosses) followed by thirteen crosses in cluster B displayed higher drought tolerance compared to the other crosses and their parental genotypes. Subsequently, these hybrids could be considered valuable candidates in future durum wheat breeding programs to develop desired segregants under water-deficit conditions. Strong positive relationships were observed between grain yield and number of grains per spike, plant height, and 1000-grain weight under water-deficit conditions. These results highlight the significance of these traits for indirect selection under drought stress conditions, particularly in the early stages of breeding, owing to their convenient measurability. [ABSTRACT FROM AUTHOR]

As a novel monoterpenoid indole alkaloid, gardneramine has been confirmed to possess excellent nervous depressive effects. However, there have been no reports about the measurement of gardneramine in vitro and in vivo. The motivation of this study was to establish and validate a specific, sensitive, and robust analytical method based on UHPLC-MS/MS for quantification of gardneramine in rat plasma and various tissues after intravenous administration. The analyte was extracted from plasma and tissue samples by protein precipitation with methanol using theophylline as an internal standard (I.S.). The analytes were separated on an Agilent ZORBAX Eclipse Plus C18 column using a gradient elution of acetonitrile and 0.1% formic acid in water at a flow rate of 0.3 mL/min. Gardneramine and I.S. were detected and quantified using positive electrospray ionization in multiple reaction monitoring (MRM) mode with transitions of m/z 413.1→217.9 for gardneramine and m/z 181.2→124.1 for I.S. Perfect linearity range was 1−2000 ng/mL with a correlation coefficient (r2) of ≥0.990. The lower limit of quantification (LLOQ) of 1.0 ng/mL was adequate for application to different preclinical studies. The method was successfully applied for determination of gardneramine in bio-samples.

A combined in silico method was developed to predict potential protein targets that are involved in cardiotoxicity induced by aconitine alkaloids and to study the quantitative structure–toxicity relationship (QSTR) of these compounds. For the prediction research, a Protein-Protein Interaction (PPI) network was built from the extraction of useful information about protein interactions connected with aconitine cardiotoxicity, based on nearly a decade of literature and the STRING database. The software Cytoscape and the PharmMapper server were utilized to screen for essential proteins in the constructed network. The Calcium-Calmodulin-Dependent Protein Kinase II alpha (CAMK2A) and gamma (CAMK2G) were identified as potential targets. To obtain a deeper insight on the relationship between the toxicity and the structure of aconitine alkaloids, the present study utilized QSAR models built in Sybyl software that possess internal robustness and external high predictions. The molecular dynamics simulation carried out here have demonstrated that aconitine alkaloids possess binding stability for the receptor CAMK2G. In conclusion, this comprehensive method will serve as a tool for following a structural modification of the aconitine alkaloids and lead to a better insight into the cardiotoxicity induced by the compounds that have similar structures to its derivatives.

A series of imidazolium salt derivatives have demonstrated potent antitumor activity in prior research. A comprehensive in silicon method was carried out to identify the putative protein target and detailed structure-activity relationship of the compounds. The Topomer CoMFA and CoMSIA techniques were implemented during the investigation to obtain the relationship between the properties of the substituent group and the contour map of around 77 compounds; the Topomer CoMFA and CoMSIA models were reliable with the statistical data. The protein-protein interaction network was constructed by combining the Pharmmapper platform and STRING database. After generating the sub-network, the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA with protein data bank ID: 3ZIM) was selected as the putative target of imidazolium salt derivatives. A docking study was carried out to correlate interactions of amino acids in protein active pockets surrounded by the ligand with contour maps generated by the structure-activity relationship method. Then the molecular dynamics simulations demonstrated that the imidazolium salt derivatives have potent binding capacity and stability to receptor 3ZIM, and the two ligand-receptor complex was stable in the last 2 ns. Finally, the ligand-based structure-activity relationship and receptor-based docking were combined together to identify the structural requirement of the imidazolium salt derivatives, which will be used to design and synthesize the novel PIK3CA inhibitors. [ABSTRACT FROM AUTHOR]