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Modeling the human brain in order to study its physiology, development and diseases has been very challenging due to its structural and functional complexity and fragility. Brain organoids, derived from human pluripotent stem cells, opened a new approach to create in vitro 3D models, that more closely resemble the complexity of the brain, as compared to 2D cell cultures. So far, multiple developmental and neurodegenerative diseases have been generated with organoid technology and used as drug screening platforms not only to accelerate the development of more efficient treatments but also to get one step closer to personalized medicine. This review aims to showcase the current applications of brain organoids and review future perspectives and limitations.

Abstract Background A wide range of studies has investigated the diagnostic proficiency of extracellular microRNAs (miRNAs) in hepatocellular cancer (HCC). HCC is expected to increase in Sub-Saharan Africa (SSA), due to endemic levels of viral infection (HBV/HIV), ageing and changing lifestyles. This unique aetiological background provides an opportunity for investigating potentially novel circulating miRNAs as biomarkers for HCC in a prospective study in South Africa. Methods This study will recruit HCC patients from two South African cancer hospitals, situated in Durban and Pietermaritzburg in the province of KwaZulu-Natal. These cases will include both HBV mono-infected and HBV/HIV co-infected HCC cases. The control group will consist of two (2) age and sex-matched healthy population controls per HCC case randomly selected from a Durban based laboratory. The controls will exclude patients if they have any evidence of chronic liver disease. A standardised reporting approach will be adopted to detect, quantify and normalize the level of circulating miRNAs in the blood sera of HCC cases and their controls. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) will be employed to quantity extracellular miRNAs. Differences in concentration of relevant miRNA by case/control status will be assessed using the Wilcoxon rank-sum (Mann-Whitney U) test. Adjustment for multiple testing (Bonferroni correction), receiver operating curves (ROC) and optimal breakpoint analyses will be employed to identify potential thresholds for the differentiation of miRNA levels of HCC cases and their controls. Discussion Although there is a growing base of literature regarding the role of circulating miRNAs as biomarkers, this promising field remains a ‘work in progress’. The aetiology of HBV infection in HCC is well understood, as well as it’s role in miRNA deregulation, however, the mediating role of HIV infection is unknown. HCC incidence in SSA, including South Africa, is expected to increase significantly in the next decade. A combination of factors, therefore, offers a unique opportunity to identify candidate circulating miRNAs as potential biomarkers for HBV/HIV infected HCC.

Objectives: To combat antimicrobial resistance, the World Health Organization (WHO) urged healthcare organizations in Low- and Middle-Income Countries (LMICs) to implement the core elements of the antimicrobial stewardship (AMS) programs. In response, Jordan took action and developed a national antimicrobial resistance action plan (NAP) in 2017 and commenced the AMS program in all healthcare facilities. It is paramount to evaluate the efforts to implement the AMS programs and understand the challenges of implementing a sustainable and effective program, in Low-Middle Income Country (LMIC) contexts. Therefore, the aim of this study was to appraise the compliance of public hospitals in Jordan to the WHO core elements of effective AMS programs after 4 years of commencement., Methods: A cross-sectional study in public hospitals in Jordan, using the WHO AMS program core elements for LMICs was carried out. The questionnaire comprised 30 questions that covered the program's six core elements: leadership commitment, accountability and responsibility, AMS actions, education and training, monitoring, and evaluation, and reporting and feedback. A five-point Likert scale was employed for each question., Results: A total of 27 public hospitals participated, with a response rate of 84.4%. Adherence to core elements ranged from (53%) in the leadership commitment domain to (72%) for AMS procedure application (actions). Based on the mean score, there was no significant difference between hospitals according to location, size, and specialty. The most neglected core elements that emerged as top priority areas were the provision of financial support, collaboration, access, as well as monitoring and evaluation., Conclusion: The current results revealed significant shortcomings in the AMS program in public hospitals despite 4 years of implementation and policy support. Most of the core elements of the AMS program were below average, which requires hospital leadership commitment, and multifaceted collaborative actions from the concerned stakeholders in Jordan., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hassan, Dahmash, Madi, Tarawneh, Jomhawi, Alkhob, Ghanem and Halasa.)

Background: The advent of the COVID-19 pandemic caused a rapid increase in demand for healthcare services over a prolonged period, and the hospital emergency preparedness system has been essential. Therefore, this study aimed to explore Jordanian hospitals' response to emergency situations and examine the underlying role and effect of accreditation programs as a "Quality and Patient Safety" tool to deal with emergency situations during the pandemic., Methods: An online survey for a cross-sectional study was conducted in Jordan between 1 March and 30 May 2022, to examine the opinions of hospitals' top, senior, and middle managers using a validated questionnaire., Results: A total of 200 healthcare providers from 30 hospitals participated in the study. From the areas within accreditation standards that were investigated, capacity building on emergency preparedness and communication abilities received the least scores (2.46 and 2.48, respectively). Additionally, hospitals with mature quality and patient safety culture (>3 accreditation cycles) demonstrated a statistically significant difference in score in two domains-emergency preparedness ( p = 0.027) and infection prevention and control ( p = 0.024)., Conclusions: During outbreaks, hospitals that are required to comply with accreditation standards that address all emergency preparedness aspects will fare better in quality performance.

During the global COVID-19 pandemic, hospitals faced tremendous pressure to cope with the emergency preparedness situations needed to cater for the influx of patients while maintaining their essential services. This study aimed to assess the level of readiness of hospitals in Jordan to respond to the COVID-19 pandemic using the WHO hospital readiness checklist. A cross-sectional survey using the modified and validated checklist was conducted in Jordan between 15 May and 15 June 2021. The checklist entailed ten key response functions with a total of 60 activities. Data from 22 hospitals were collected through a structured survey process by two surveyors for each hospital. The overall readiness score of hospitals was 1.77 ± 0.20, with a lower overall score in the northern region (1.65 ± 0.24) than the middle (1.86 ± 0.07) or southern (1.84 ± 0.14) regions. The diagnosis response function scored highest (1.95); but despite efforts, contingency plan development was not met by most hospitals, with a total score ≤ 1.45. Provision of psychological support and occupational health support to ensure the wellbeing of staff scored below average. Outcomes from this survey exposed gaps while offering a framework for upcoming endeavors to improve hospital readiness for any potential pandemic.

Objective: This study aimed at investigating HCWs' perceptions of PPE compliance and barriers, as well as influencing factors, in order to develop methods to combat the rise in their infection rates., Methods: During the 'second wave' surge, a cross-sectional correlational analysis was conducted over a 1-month period. It consists of HCWs from various hospital sectors that admit COVID-19 patients using an online self-administered predesigned tool., Results: Out of the 285 recruited participants, 36.1% had previously been diagnosed with COVID-19. Around 71% received training on PPE use. The perceived compliance was good for (PPE) usage (mean 2.60 ± 1.10). A significant higher compliance level was correlated with previous diagnosis with COVID-19, working with patients diagnosed with COVID-19, and having a direct contact with a family member older than 45 years old (P < 0.01). The main perceived barriers to the use of PPEs were unavailability of full PPEs (35%), interference with their ability to provide patient care (29%), not enough time to comply with the rigors of PPEs (23.2%) and working in emergency situations (22.5%). With regards to perceived barriers, those working with patients diagnosed with COVID-19 and those who reported having a direct contact with a family member older than 45 years old showed significantly higher level of barriers., Conclusion: A series of measures, including prioritization of PPE acquisition, training, and monitoring to guarantee appropriate resources for IPC, are necessary to reduce transmission.

With cancer being the third leading cause of mortality in the United Arab Emirates (UAE), there has been significant investment from the government and private health care providers to enhance the quality of cancer care in the UAE. The UAE is a developing country with solid economic resources that can be utilized to improve cancer care across the country. There is limited data regarding the incidence, survival, and potential risk factors for cancer in the UAE. The UAE Oncology Task Force was established in 2019 by cancer care providers from across the UAE under the auspices of Emirates Oncology Society. In this paper we summarize the history of cancer care in the UAE, report the national cancer incidence, and outline current challenges and opportunities to enhance and standardize cancer care. We provide recommendations for policymakers and the UAE Oncology community for the delivery of high-quality cancer care. These recommendations are aligned with the UAE government's vision to reduce cancer mortality and provide high quality healthcare for its citizens.

There is growing interest in the application of human-associated fecal source identification quantitative real-time PCR (qPCR) technologies for water quality management. The transition from a research tool to a standardized protocol requires a high degree of confidence in data quality across laboratories. Data quality is typically determined through a series of specifications that ensure good experimental practice and the absence of bias in the results due to DNA isolation and amplification interferences. However, there is currently a lack of consensus on how best to evaluate and interpret human fecal source identification qPCR experiments. This is, in part, due to the lack of standardized protocols and information on interlaboratory variability under conditions for data acceptance. The aim of this study is to provide users and reviewers with a complete series of conditions for data acceptance derived from a multiple laboratory data set using standardized procedures. To establish these benchmarks, data from HF183/BacR287 and HumM2 human-associated qPCR methods were generated across 14 laboratories. Each laboratory followed a standardized protocol utilizing the same lot of reference DNA materials, DNA isolation kits, amplification reagents, and test samples to generate comparable data. After removal of outliers, a nested analysis of variance (ANOVA) was used to establish proficiency metrics that include lab-to-lab, replicate testing within a lab, and random error for amplification inhibition and sample processing controls. Other data acceptance measurements included extraneous DNA contamination assessments (no-template and extraction blank controls) and calibration model performance (correlation coefficient, amplification efficiency, and lower limit of quantification). To demonstrate the implementation of the proposed standardized protocols and data acceptance criteria, comparable data from two additional laboratories were reviewed. The data acceptance criteria proposed in this study should help scientists, managers, reviewers, and the public evaluate the technical quality of future findings against an established benchmark., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Some molecular methods for tracking fecal pollution in environmental waters have both PCR and quantitative PCR (qPCR) assays available for use. To assist managers in deciding whether to implement newer qPCR techniques in routine monitoring programs, we compared detection limits (LODs) and costs of PCR and qPCR assays with identical targets that are relevant to beach water quality assessment. For human-associated assays targeting Bacteroidales HF183 genetic marker, qPCR LODs were 70 times lower and there was no effect of target matrix (artificial freshwater, environmental creek water, and environmental marine water) on PCR or qPCR LODs. The PCR startup and annual costs were the lowest, while the per reaction cost was 62% lower than the Taqman based qPCR and 180% higher than the SYBR based qPCR. For gull-associated assays, there was no significant difference between PCR and qPCR LODs, target matrix did not effect PCR or qPCR LODs, and PCR startup, annual, and per reaction costs were lower. Upgrading to qPCR involves greater startup and annual costs, but this increase may be justified in the case of the human-associated assays with lower detection limits and reduced cost per sample., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A number of PCR-based methods for detecting human fecal material in environmental waters have been developed over the past decade, but these methods have rarely received independent comparative testing in large multi-laboratory studies. Here, we evaluated ten of these methods (BacH, BacHum-UCD, Bacteroides thetaiotaomicron (BtH), BsteriF1, gyrB, HF183 endpoint, HF183 SYBR, HF183 Taqman(®), HumM2, and Methanobrevibacter smithii nifH (Mnif)) using 64 blind samples prepared in one laboratory. The blind samples contained either one or two fecal sources from human, wastewater or non-human sources. The assay results were assessed for presence/absence of the human markers and also quantitatively while varying the following: 1) classification of samples that were detected but not quantifiable (DNQ) as positive or negative; 2) reference fecal sample concentration unit of measure (such as culturable indicator bacteria, wet mass, total DNA, etc); and 3) human fecal source type (stool, sewage or septage). Assay performance using presence/absence metrics was found to depend on the classification of DNQ samples. The assays that performed best quantitatively varied based on the fecal concentration unit of measure and laboratory protocol. All methods were consistently more sensitive to human stools compared to sewage or septage in both the presence/absence and quantitative analysis. Overall, HF183 Taqman(®) was found to be the most effective marker of human fecal contamination in this California-based study., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The goal of this study is to explore the application of epigenetic markers in the identification of biofluids that are commonly found at the crime scene. A series of genetic loci were examined in order to define epigenetic markers that display differential methylation patterns between blood, saliva, semen, and epithelial tissue. Among the different loci tested, we have identified a panel of markers, C20orf117, ZC3H12D, BCAS4, and FGF7, that can be used in the determination of these four tissue types. Since methylation modifications occur at cytosine bases that are immediately followed by guanine bases (CpG sites), methylation levels were measured at CpG sites spanning each marker. Up to 11 samples of each tissue type were collected and subjected to bisulfite modification to convert unmethylated CpG-associated cytosine bases to thymine bases. The bisulfite modified DNA was then amplified via nested PCR using a primer set of which one primer was biotin labeled. Biotinylated PCR products were in turn analyzed and the methylation level at each CpG site was quantitated by pyrosequencing. The percent methylation values at each CpG site were determined and averaged for each tissue type. The results indicated significant methylation differences between the tissue types. The methylation patterns at the ZC3H12D and FGF7 loci differentiated sperm from blood, saliva, and epithelial cells. The C20orf117 locus differentiated blood from sperm, saliva, and epithelial cells and saliva was differentiated from blood, sperm, and epithelial cells at a fourth locus, BCAS4. The results of this study demonstrate the applicability of epigenetic markers as a novel tool for the determination of biofluids using bisulfite modification and pyrosequencing., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The high energy density of electronic excitations due to the impact of swift heavy ions can induce structural modifications in materials. We present an x-ray diffractometer called ALIX ("Analyse en Ligne sur IRRSUD par diffraction de rayons X"), which has been set up at the low-energy beamline (IRRadiation SUD - IRRSUD) of the Grand Accélérateur National d'Ions Lourds facility, to allow the study of structural modification kinetics as a function of the ion fluence. The x-ray setup has been modified and optimized to enable irradiation by swift heavy ions simultaneously to x-ray pattern recording. We present the capability of ALIX to perform simultaneous irradiation-diffraction by using energy discrimination between x-rays from diffraction and from ion-target interaction. To illustrate its potential, results of sequential or simultaneous irradiation-diffraction are presented in this article to show radiation effects on the structural properties of ceramics. Phase transition kinetics have been studied during xenon ion irradiation of polycrystalline MgO and SrTiO(3). We have observed that MgO oxide is radiation-resistant to high electronic excitations, contrary to the high sensitivity of SrTiO(3), which exhibits transition from the crystalline to the amorphous state during irradiation. By interpreting the amorphization kinetics of SrTiO(3), defect overlapping models are discussed as well as latent track characteristics. Together with a transmission electron microscopy study, we conclude that a single impact model describes the phase transition mechanism.

Background: The RTS,S/AS01(E) candidate malaria vaccine is being developed for immunisation of infants in Africa through the expanded programme on immunisation (EPI). 8 month follow-up data have been reported for safety and immunogenicity of RTS,S/AS01(E) when integrated into the EPI. We report extended follow-up to 19 months, including efficacy results., Methods: We did a randomised, open-label, phase 2 trial of safety and efficacy of the RTS,S/AS01(E) candidate malaria vaccine given with EPI vaccines between April 30, 2007, and Oct 7, 2009, in Ghana, Tanzania, and Gabon. Eligible children were 6-10 weeks of age at first vaccination, without serious acute or chronic illness. All children received the EPI diphtheria, tetanus, pertussis (inactivated whole-cell), and hepatitis-B vaccines, Haemophilus influenzae type b vaccine, and oral polio vaccine at study months 0, 1, and 2, and measles vaccine and yellow fever vaccines at study month 7. Participants were randomly assigned (1:1:1) to receive three doses of RTS,S/AS01(E) at 6, 10, and 14 weeks (0, 1, 2 month schedule) or at 6 weeks, 10 weeks, and 9 months (0, 2, 7 month schedule) or placebo. Randomisation was according to a predefined block list with a computer-generated randomisation code. Detection of serious adverse events and malaria was by passive case detection. Antibodies against Plasmodium falciparum circumsporozoite protein and HBsAg were monitored for 19 months. This study is registered with ClinicalTrials.gov, number NCT00436007., Findings: 511 children were enrolled. Serious adverse events occurred in 57 participants in the RTS,S/AS01(E) 0, 1, 2 month group (34%, 95% CI 27-41), 47 in the 0, 1, 7 month group (28%, 21-35), and 49 (29%, 22-36) in the control group; none were judged to be related to study vaccination. At month 19, anticircumsporozoite immune responses were significantly higher in the RTS,S/AS01(E) groups than in the control group. Vaccine efficacy for the 0, 1, 2 month schedule (2 weeks after dose three to month 19, site-adjusted according-to-protocol analysis) was 53% (95% CI 26-70; p=0·0012) against first malaria episodes and 59% (36-74; p=0·0001) against all malaria episodes. For the entire study period, (total vaccinated cohort) vaccine efficacy against all malaria episodes was higher with the 0, 1, 2 month schedule (57%, 95% CI 33-73; p=0·0002) than with the 0, 1, 7 month schedule (32% CI 16-45; p=0·0003). 1 year after dose three, vaccine efficacy against first malaria episodes was similar for both schedules (0, 1, 2 month group, 61·6% [95% CI 35·6-77·1], p<0·001; 0, 1, 7 month group, 63·8% [40·4-78·0], p<0·001, according-to-protocol cohort)., Interpretation: Vaccine efficacy was consistent with the target put forward by the WHO-sponsored malaria vaccine technology roadmap for a first-generation malaria vaccine. The 0, 1, 2 month vaccine schedule has been selected for phase 3 candidate vaccine assessment., Funding: Program for Appropriate Technology in Health Malaria Vaccine Initiative; GlaxoSmithKline Biologicals., (Copyright © 2011 Elsevier Ltd. All rights reserved.)