The Regulatory Review Process in South Africa: Challenges and Opportunities for a New Improved System.

BACKGROUND: The aims of this study were to assess the regulatory review process in South Africa from 2015 to 2017, identify the key milestones and timelines; evaluate the effectiveness of measures to ensure consistency, transparency, timeliness, and predictability in the review process; and to provide recommendations for enhanced regulatory practices. METHODS: A questionnaire was completed by the Medicines Control Council (MCC) to describe the organization of the authority, record key milestones and timelines in the review process and to identify good review practices (GRevPs). RESULTS: Currently, the MCC conducts a full assessment of quality, efficacy, and safety data in the review of all applications. The overall regulatory median approval time decreased by 14% in 2017 (1411 calendar days) compared with that of 2016, despite the 27% increase in the number of applications. However, the MCC has no target for overall approval time of new active substance applications and no targets for key review milestones. Guidelines, standard operating procedures, and review templates are in place, while the formal implementation of GRevPs and the application of an electronic document management system are planned for the near future. CONCLUSIONS: As the MCC transitions to the newly established South Africa Health Products Regulatory Authority, it would be crucial for the authority to recognize the opportunities for an enhanced regulatory review and should consider models such as abridged assessment, which encompass elements of risk stratification and reliance. It is hoped that resource constraints may then be alleviated and capacity developed to meet target timelines.Peer reviewedFinal Published versio

Predicting a Mathematical Models of Some Mechanical Properties of Concrete from Non-Destructive Testing

Nondestructive tests NDT are considered as a one of the methods of evaluation and quality control of concrete. The fundamental aim of the present study is constructing a mathematical models  to predict some mechanical properties  of concrete from Nondestructive testing, in addition the study of (NSC and HSC) properties (density, compressive strength ,modulus of elasticity and modulus of rupture ) of concrete grade (20-100) MPa) by using NDT methods namely; Schmidt Hammer test (RN )and Ultrasonic Pulse Velocity test ( UPV) with destructive test methods at different four ages (7, 28, 56 and 90) days. This study  used  ready mixes (1:2:4 and 1:1.5:3) and design mixes (C40, C50, C60, C70, C80, C90 and C100), in order to find  the relationship between these properties. of concrete with (RN and UPV), and compressive strength  of concrete-combined NDT(RN and UPV) relationship, for all mixes (as freelance and as group). The results of compressive strength for both types of concrete NSC and HSC exhibit an increase with the increase of bulk density and time of curing. Also, the results show a good correlation between compressive strength and (RN) and the relationship between the two is not affected by maximum aggregate size (MAS). Also, a good correlation between compressive strength and Ultrasonic Pulse Velocity (UPV) and The value of UPV in HSC increased 8% from 28 days to 90 days. Also, the results indicated that the percentages of increase in relationship between static modulus of elasticity and compressive strength for 28 days to 90 days are 15% at low strength, 5.6% at high strength and the relationship between static modulus of elasticity and rebound number for 28 days to 90 days is3.3%.The results indicate that the percentage of increase in direct method to surfacing method of UPV for (7, 28, 56 and 90) days is (7%, 5%, 4% and 3.5%) respectively, due to the higher the continuity of hydration of cement.  Also, the pulse velocity of concrete is decreased by increasing the cement paste, especially for concrete with high w/c. Keywords— Nondestructive tests, Schmidt hammer test(RN), Ultrasonic pulse velocity test  ( UPV) , Density , Compressive strength, modulus of elasticity , modulus of rupture

Sequence analysis of the VSX1 and SOD1 genes in families with Keratoconus and a review of the literature

AbstractObjectiveKeratoconus (KC) is a non-inflammatory disorder of the cornea in which the cornea becomes thin and conical, inducing myopia and irregular astigmatism and resulting in mild to marked impairment of vision. The present study was designed to screen two candidate KC genes to identify pathogenic sequence variants responsible for KC in Saudi families.MethodsPeripheral blood samples from members of five Saudi families with KC from the Northern region were collected. Genomic DNA was isolated, and bidirectional sequencing was performed of all coding exons of VSX1 and SOD1 genes using Sanger sequencing.ResultsAll five of the KC families showed a pattern of autosomal recessive inheritance. Phenotyping of these families was performed by a senior ophthalmologist. Sequence analysis of the VSX1 and SOD1 genes failed to reveal any pathogenic sequence variant that could account for KC in the affected individuals.ConclusionOur failure to detect sequence variants in two of the known KC associated genes triggers an interest in other known KC candidate genes, including miR-184, DOCK9, IL1RN and SLC4A11. Future genotyping with dense SNP arrays followed by exome sequencing in these families will be a useful approach to identify the gene(s) underlying KC in this Saudi cohort, which may be different from those reported elsewhere

The influence of community on Transient evoked otoacoustic emissions (TEOAEs) in Iraqi subjects with normal hearing.

Background: The purpose of this study was to compare the parametric measurements of transient otoacoustic (TEOAEs) in normal hearing subjects between two clinical centers in Iraq and to examine the community effect on TEOAEs characteristics. Patients and Methods: Transient otoacoustic emission (TEOAEs) were obtained from eighty subjects (160 ears)-males and females aged (10-20 years), with Forty (40) subjects in Baghdad audiology center and forty subjects in Sulaimania audiology center (North of Iraq)[ Kurdistan-Iraq], in standard, non-linear “Fast Screen” mode. Hearing thresholds, tympanometric, and TEOAE-parameters were recorded between two clinical center groups. Results: The cross correlation (wave reproducibility) was constant between two groups. The mean Signal to noise ratio (SNRs) for all (160 ears) were well above 3 dB at frequencies 1K, 2K, 3K, 4K and 5 KHz. The Sulaimania –subjects group showed the lowest SNR in low frequency (1 KHz) and middle frequency (3 KHz) than the Baghdad-subjects group. No statistical difference was observed in other frequency bands, and in overall mean SNRs between two groups. Conclusions: The observed differences of SNRs at low and middle frequency bands are most likely related to differences in ear canal volume and/or to differences in cochlear mechanisms. The values obtained in the present study can be used as normative data for screening and diagnostic purposes in Iraqi subjects aged (10-20 years)

Methylphenidate improves executive functions in patients with traumatic brain injuries : a feasibility trial via the idiographic approach

Background: Road traffic accidents are known to be the main cause of traumatic brain injury (TBI). TBI is also a leading cause of death and disability. This study, by means of the idiographic approach (single-case experimental designs using multiple-baseline designs), has examined whether methylphenidate (MPH - trade name Ritalin) had a differential effect on cognitive measures among patients with TBI with the sequel of acute and chronic post-concussion syndromes. The effect on gender was also explored. Methods: In comparison with healthy controls, patients with TBI (acute and chronic) and accompanying mild cognitive impairment (MCI) were screened for their integrity of executive functioning. Twenty-four patients exhibiting executive dysfunction (ED) were then instituted with the pharmacological intervention methylphenidate (MPH). The methylphenidate was administered using an uncontrolled, open label design. Results: The administration of methylphenidate impacted ED in the TBI group but had no effect on mood. Attenuation of ED was more apparent in the chronic phases of TBI. The effect on gender was not statistically significant with regard to the observed changes. Conclusions: To our knowledge, this is the first feasibility trial from the Arabian Gulf to report the performance of a TBI population with mild cognitive impairment according to the IQCODE Arabic version. This investigation confirms anecdotal observations of methylphenidate having the potential to attenuate cognitive impairment; particularly those functions that are critically involved in the integrity of executive functioning. The present feasibility trial should be followed by nomothetic studies such as those that adhere to the protocol of the randomized controlled trial. This evidence-based research is the foundation for intervention and future resource allocation by policy- or public health decision-makers

Copy number variations residing outside the SHOX enhancer region are involved in Short Stature and Léri-Weill dyschondrosteosis

Background: SHOX enhancer CNVs, affecting one or more of the seven recognized evolutionary conserved non-coding elements (CNEs) represent one of the most frequent cause of SHOX-haploinsufficiency. During the diagnostic workflow deletions/duplications have been identified downstream SHOX not including any of the these CNEs. Methods: Fine tiling aCGH and breakpoint PCR were used to characterize the critical interval and to search for novel alterations in a cohort of selected patients. Results: Screening of 252 controls provided evidence that duplications in this area represent likely benign variants whereas none of the deletions were detected. These findings suggested that other alterations relevant for SHOX-haploinsufficiency might be missed by the standard diagnostic methods. To identify such undisclosed elements, the aCGH was used to reanalyze 52 unresolved cases with clinical features strongly suggestive of SHOX-haploinsufficiency. This analysis followed by the screening of 210 patients detected two partially overlapping small deletions of ~12 and ~8 kb in four unrelated individuals, approximately 15 kb downstream SHOX, that were absent in 720 normal stature individuals. Conclusion: Our results strengthen the hypothesis that alterations of yet unidentified cis-regulatory elements residing outside those investigated through conventional methods, might explain the phenotype in ISS/LWD patients thus enlarging the spectrum of variants contributing to SHOX-haploinsufficiency

Post-COVID-19 fatigue and health-related quality of life in Saudi Arabia: a population-based study

BackgroundDespite substantial literature on symptoms and long-term health implications associated with COVID-19; prevalence and determinants of post-acute COVID-19 fatigue (PCF) remain largely elusive and understudied, with scant research documenting health-related quality of life (HRQoL). Hence, prevalence of PCF and its associated factors, and HRQoL among those who have survived Covid-19 within the general population of Saudi Arabia (KSA) is the subject under examination in this research.MethodsThis cross-sectional study was conducted on 2063 individuals, selected from the KSA’s general population, using a non-probability sampling approach. An online survey was used to employ a self-administered questionnaire to the participants, which included socio-demographic information, the patient’s COVID-19 infection history, 12-item Short Form Health Survey (SF-12) to assess quality of life, and Chalder Fatigue Scale (CFS) (CFQ 11) to evaluate the extent and severity of fatigue. Data were analyzed using SPSS version 26. A p < 0.05 was considered to be strong evidence against the null hypothesis.ResultsThe median age of participants was 34 (IQR = 22) years, with females comprising the majority (66.2%). According to the SF-12 questionnaire, 91.2% of patients experienced physical conditions, and 77% experienced depression. The prevalence of PCF was 52% on CFQ 11 scale. Female gender, higher levels of education, a pre-existing history of chronic disease, as well as the manifestations of shortness of breath and confusion during acute COVID-19 infection, were identified as independent predictors of fatigue.ConclusionTo facilitate timely and effective intervention for post-acute COVID-19 fatigue, it is essential to continuously monitor the individuals who have recovered from acute COVID-19 infection. Also, it is critical to raise health-education among these patients to improve their quality of life. Future research is required to determine whether COVID-19 survivors would experience fatigue for an extended duration and the impact of existing interventions on its prevalence and severity

A Systemic Review of Iron Deficiency Anemia in Adults and the Clinical Management of Diagnosis and Treatment

Iron deficiency is the most frequent cause of anaemia worldwide. It impairs quality of life, increases asthenia and can lead to clinical worsening of patients. In addition, iron deficiency has a complex mechanism whose pathologic pathway is recently becoming better understood. The discovery of hepcidin has allowed a better clarification of iron metabolism regulation. Furthermore, the ratio of concentration of soluble transferrin receptor to the log of the ferritin level, has been developed as a tool to detect iron deficiency in most situations. Therefore, the problem of this research lies in exploring the cause of iron deficiency that always be sought because the underlying condition can be serious. This review will summarize the current knowledge regarding diagnostic algorithms for iron deficiency anemia. The majority of aetiologies occur in the digestive tract, and justify morphological examination of the gut. First line investigations are upper gastrointestinal endoscopy and colonoscopy, and when negative, the small bowel should be explored; newer tools such as video capsule endoscopy have also been developed. The treatment of iron deficiency is aetiological if possible and iron supplementation whether in oral or in parenteral form

Biodegradation of Some Polycyclic Aromatic Hydrocarbons by a Bacterial Consortium Isolated from the Red Sea of Jeddah

Polycyclic aromatic hydrocarbons (PAHs) are considered organic pollutants, which are stable, highly toxic, and carcinogenic. Therefore, it was necessary to find an environmentally friendly way to degrade these compounds and remove them from polluted environments. Water samples polluted with petroleum hydrocarbons were collected from the coast of Jeddah on the Red Sea - Saudi Arabia. The results of the current study showed the ability of bacterial consortium that was enriched from the coast of Jeddah, Saudi Arabia to degrade petroleum hydrocarbons wastewater, which proved its ability to degrade PAHs in saline conditions. The bacterial union degraded BENZ compound by more than 95% at the concentration of 100 and 250 mg/L, while the degradation of this compound at the concentration of 1000 mg/L was recorded about 83% while the ANT degradation rate was recorded at more than 90% at different concentrations. In addition, this study revealed the ability of bacterial consortium to treat petroleum hydrocarbons wastewater in bioreactor (CSTR) with 92.7% of COD removed under saline conditions. Hence, this study recommends the investment of bacterial consortium in the treatment of petroleum hydrocarbons wastewater in marine environments and to remove pollutants from them

Cyanobacteria—From the Oceans to the Potential Biotechnological and Biomedical Applications

Cyanobacteria are photosynthetic prokaryotic organisms which represent a significantsource of novel, bioactive, secondary metabolites, and they are also considered an abundant source ofbioactive compounds/drugs, such as dolastatin, cryptophycin 1, curacin toyocamycin, phytoalexin,cyanovirin-N and phycocyanin. Some of these compounds have displayed promising results insuccessful Phase I, II, III and IV clinical trials. Additionally, the cyanobacterial compounds applied tomedical research have demonstrated an exciting future with great potential to be developed into newmedicines. Most of these compounds have exhibited strong pharmacological activities, includingneurotoxicity, cytotoxicity and antiviral activity against HCMV, HSV-1, HHV-6 and HIV-1, so thesemetabolites could be promising candidates for COVID-19 treatment. Therefore, the effective large-scale production of natural marine products through synthesis is important for resolving the existingissues associated with chemical isolation, including small yields, and may be necessary to betterinvestigate their biological activities. Herein, we highlight the total synthesized and stereochemicaldeterminations of the cyanobacterial bioactive compounds. Furthermore, this review primarilyfocuses on the biotechnological applications of cyanobacteria, including applications as cosmetics,food supplements, and the nanobiotechnological applications of cyanobacterial bioactive compoundsin potential medicinal applications for various human diseases are discussed.Stockholm UniversityPeer Reviewe