Towards a digitized and integrated health information system in Sudan: assessment of readiness at state level

Background: A strong health information system able to generate timely and accurate information is essential to ensure effective and efficient performance. Sudan’s health information system is still paper-based and characterized by fragmentation and verticality. Efforts to overcome this have led to development of an integrated system to digitize the health information. For this to succeed the 18 states in Sudan need to be evaluated and assessed to identify the gaps in capacity and readiness for such important change. The aim of this paper is to assess the capacity and readiness of the health information system in Sudan at state level for the digitization of the health information system.Materials and Methods: This is a cross sectional institutional based study conducted in 2014 targeting the health information units in the 18 states ministries of health in Sudan. Quantitative data was collected using a pre-tested checklist and analyzed using SPSS version 20. Qualitative data was collected through semi-structured interviews with state managers and analyzed using the evaluation matrix.Results: All states ministries of health had health information units but this was believed inadequate in 27.8% and 72.2% had units at locality level. Data analysis units were not present in one third of the states. Basic statistical training was done in 15 states. Internet services was available in 14 states but was scarce at locality level (16.7%). Annual reports though produced by 17 states, one third admit not reporting to higher levels in a regular manner.Conclusion: There is a need to strengthen the health information system at state level. Challenges of ICT infrastructure, capacity building and coordination need to be addressed. This needs collaborative work and political commitment.Keywords: Health Information System, states, digitizatio

Exploiting an Elitist Barnacles Mating Optimizer implementation for substitution box optimization

Barnacles Mating Optimizer (BMO) is a new metaheuristic algorithm that suffers from slow convergence and poor efficiency due to its limited capability in exploiting the search space and exploring new promising regions. Addressing these shortcomings, this paper introduces Elitist Barnacles Mating Optimizer (eBMO). Unlike BMO, eBMO exploits the elite exponential probability (Pelite) to decide whether to intensify search process via swap operator or to diversify search by randomly exploring new regions. Furthermore, eBMO uses Chebyshev map instead of random numbers to generate quality S-boxes. Experimental results of eBMO on the generation of 8 × 8 substitution-box are competitive against other existing works

Intelligent ultra-light deep learning model for multi-class brain tumor detection

The diagnosis and surgical resection using Magnetic Resonance (MR) images in brain tumors is a challenging task to minimize the neurological defects after surgery owing to the non-linear nature of the size, shape, and textural variation. Radiologists, clinical experts, and brain surgeons examine brain MRI scans using the available methods, which are tedious, error-prone, time-consuming, and still exhibit positional accuracy up to 2−3 mm, which is very high in the case of brain cells. In this context, we propose an automated Ultra-Light Brain Tumor Detection (UL-BTD) system based on a novel Ultra-Light Deep Learning Architecture (UL-DLA) for deep features, integrated with highly distinctive textural features, extracted by Gray Level Co-occurrence Matrix (GLCM). It forms a Hybrid Feature Space (HFS), which is used for tumor detection using Support Vector Machine (SVM), culminating in high prediction accuracy and optimum false negatives with limited network size to fit within the average GPU resources of a modern PC system. The objective of this study is to categorize multi-class publicly available MRI brain tumor datasets with a minimum time thus real-time tumor detection can be carried out without compromising accuracy. Our proposed framework includes a sensitivity analysis of image size, One-versus-All and One-versus-One coding schemes with stringent efforts to assess the complexity and reliability performance of the proposed system with K-fold cross-validation as a part of the evaluation protocol. The best generalization achieved using SVM has an average detection rate of 99.23% (99.18%, 98.86%, and 99.67%), and F-measure of 0.99 (0.99, 0.98, and 0.99) for (glioma, meningioma, and pituitary tumors), respectively. Our results have been found to improve the state-of-the-art (97.30%) by 2%, indicating that the system exhibits capability for translation in modern hospitals during real-time surgical brain applications. The method needs 11.69 ms with an accuracy of 99.23% compared to 15 ms achieved by the state-of-the-art to earlier to detect tumors on a test image without any dedicated hardware providing a route for a desktop application in brain surgery

Novel engineered nanobodies specific for N-terminal region of alpha-synuclein recognize Lewy-body pathology and inhibit in-vitro seeded aggregation and toxicity.

Nanobodies (Nbs), the single-domain antigen-binding fragments of dromedary heavy-chain antibodies (HCAb), are excellent candidates as therapeutic and diagnostic tools in synucleinopathies because of their small size, solubility and stability. Here, we constructed an immune nanobody library specific to the monomeric form of alpha-synuclein (α-syn). Phage display screening of the library allowed the identification of a nanobody, Nbα-syn01, specific for α-syn. Unlike previously developed nanobodies, Nbα-syn01 recognized the N-terminal region which is critical for in vitro and in vivo aggregation and contains many point mutations involved in early PD cases. The affinity of the monovalent Nbα-syn01 and the engineered bivalent format BivNbα-syn01 measured by isothermal titration calorimetry revealed unexpected results where Nbα-syn01 and its bivalent format recognized preferentially α-syn fibrils compared to the monomeric form. Nbα-syn01 and BivNbα-syn01 were also able to inhibit α-syn-seeded aggregation in vitro and reduced α-syn-seeded aggregation and toxicity in cells showing their potential to reduce α-syn pathology. Moreover, both nanobody formats were able to recognize Lewy-body pathology in human post-mortem brain tissue from PD and DLB cases. Additionally, we present evidence through structural docking that Nbα-syn01 binds the N-terminal region of the α-syn aggregated form. Overall, these results highlight the potential of Nbα-syn01 and BivNbα-syn01 in developing into a diagnostic or a therapeutic tool for PD and related disorders

Signal transducer and activator of transcription 3 (Stat3) suppresses stat1/interferon signaling pathway and inflammation in senescent preadipocytes

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. Obesity promotes premature aging and dysfunction of white adipose tissue (WAT) through the accumulation of cellular senescence. The senescent cells burden in WAT has been linked to inflammation, insulin‐resistance (IR), and type 2 diabetes (T2D). There is limited knowledge about molecular mechanisms that sustain inflammation in obese states. Here, we describe a robust and physiologically relevant in vitro system to trigger senescence in mouse 3T3‐L1 preadipocytes. By employing transcriptomics analyses, we discovered up‐regulation of key pro‐inflammatory molecules and activation of interferon/signal transducer and activator of transcription (STAT)1/3 signaling in senescent preadipocytes, and expression of downstream targets was induced in epididymal WAT of obese mice, and obese human adipose tissue. To test the relevance of STAT1/3 signaling to preadipocyte senescence, we used Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9 (CRISPR/Cas9) technology to delete STAT1/3 and discovered that STAT1 promoted growth arrest and cooperated with cyclic Guanosine Monophosphate‐Adenosine Monophosphate (GMP‐AMP) synthase‐stimulator of interferon genes (cGAS‐STING) to drive the expression of interferon β (IFNβ), C‐X‐C motif chemokine ligand 10 (CXCL10), and interferon signaling‐related genes. In contrast, we discovered that STAT3 was a negative regulator of STAT1/cGAS‐STING signaling—it suppressed senescence and inflammation. These data provide insights into how STAT1/STAT3 signaling coordinates senescence and inflammation through functional interactions with the cGAS/STING pathway

Fibrillar form of α-synuclein-specific scFv antibody inhibits α-synuclein seeds induced aggregation and toxicity

Synucleinopathies including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are characterized by pathological accumulation of α-synuclein (α-syn). Amongst the various approaches attempting to tackle the pathological features of synucleinopathies, antibody-based immunotherapy holds much promise. However, the large size of antibodies and corresponding difficulty in crossing the blood-brain barrier has limited development in this area. To overcome this issue, we engineered single-chain variable fragments (scFvs) against fibrillar α-syn, a putative disease-relevant form of α-syn. The purified scFvs showed specific activity towards α-syn fibrils and oligomers in comparison to monomers and recognized intracellular inclusions in human post-mortem brain tissue of Lewy body disease cases, but not aged controls. In vitro studies indicated scFvs inhibit the seeding of α-syn aggregation in a time-dependent manner, decreased α-syn seed-induced toxicity in a cell model of PD, and reduced the production of insoluble α-syn phosphorylated at Ser-129 (pS129-α-syn). These results suggest that our α-syn fibril-specific scFvs recognize α-syn pathology and can inhibit the aggregation of α-syn in vitro and prevent seeding-dependent toxicity. Therefore, the scFvs described here have considerable potential to be utilized towards immunotherapy in synucleinopathies and may also have applications in ante-mortem imaging modalities.Dr. El-Agnaf’s laboratory was funded by Qatar Biomedical Research Institute under the Start-up Fund SF 2017– 007. The Newcastle Brain Tissue Resource is funded in part by a grant from the UK Medical Research Council, by NIHR Newcastle Biomedical Research Centre awarded to the Newcastle upon Tyne NHS Foundation Trust and Newcastle University, and by a grant from the Alzheimer’s Society and Alzheimer’s Research UK as part of the Brains for Dementia Research Project

Characterizing the morbid genome of ciliopathies

Background Ciliopathies are clinically diverse disorders of the primary cilium. Remarkable progress has been made in understanding the molecular basis of these genetically heterogeneous conditions; however, our knowledge of their morbid genome, pleiotropy, and variable expressivity remains incomplete. Results We applied genomic approaches on a large patient cohort of 371 affected individuals from 265 families, with phenotypes that span the entire ciliopathy spectrum. Likely causal mutations in previously described ciliopathy genes were identified in 85% (225/265) of the families, adding 32 novel alleles. Consistent with a fully penetrant model for these genes, we found no significant difference in their “mutation load” beyond the causal variants between our ciliopathy cohort and a control non-ciliopathy cohort. Genomic analysis of our cohort further identified mutations in a novel morbid gene TXNDC15, encoding a thiol isomerase, based on independent loss of function mutations in individuals with a consistent ciliopathy phenotype (Meckel-Gruber syndrome) and a functional effect of its deficiency on ciliary signaling. Our study also highlighted seven novel candidate genes (TRAPPC3, EXOC3L2, FAM98C, C17orf61, LRRCC1, NEK4, and CELSR2) some of which have established links to ciliogenesis. Finally, we show that the morbid genome of ciliopathies encompasses many founder mutations, the combined carrier frequency of which accounts for a high disease burden in the study population. Conclusions Our study increases our understanding of the morbid genome of ciliopathies. We also provide the strongest evidence, to date, in support of the classical Mendelian inheritance of Bardet-Biedl syndrome and other ciliopathies

Synthesis and pharmacological activities of some condensed 4-chloro-2,2-dialkyl chromene-3-carbaldehyde derivatives

Novi hidrazono- 5a,b, tiosemikarbazono- 6a-c i oksimo kromeni 7a-c sintetizirani su iz odgovarajućeg β-klorkarbaldehida 3 i hidrazina, aromatskog hidrazina, tiosemikarbazida ili hidroksilamin hidroklorida, dok su eterski derivati 8a-h pripremljeni iz pripadajućih aldoksima 7a-c. Novi spojevi ispitani su na protuupalno i ulcerogeno djelovanje, a njihovo djelovanje uspoređeno je s djelovanjem indometacina.Some new hydrazono- 5a,b, thiosemicarbazono- 6a-c, and oximo chromenes 7a-c were prepared via the reaction of the corresponding β-chlorocarbaldehyde 3 with hydrazine, aromatic hydrazine, thiosemicarbazide and hydroxylamine hydrochloride, respectively. In addition, ether derivatives 8a-h were prepared from the corresponding aldoximes 7a-c. The new products were tested for anti-inflammatory and ulcerogenic score activities compared to indomethacin

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely