Efficient Synthesis of Fe3O4/PPy Double-Carbonized Core-Shell-like Composites for Broadband Electromagnetic Wave Absorption.

Ever-increasing electromagnetic pollution largely affects human health, sensitive electronic equipment, and even military security, but current strategies used for developing functional attenuation materials cannot be achieved in a facile and cost-effective way. Here, a unique core-shell-like composite was successfully synthesized by a simple chemical approach and a rapid microwave-assisted carbonization process. The obtained composites show exceptional electromagnetic wave absorption (EMWA) properties, including a wide effective absorption band (EAB) of 4.64 GHz and a minimum reflection loss (RLmin) of -26 dB at 1.6 mm. The excellent performance can be attributed to the synergistic effects of conductive loss, dielectric loss, magnetic loss, and multiple reflection loss within the graphene-based core-shell-like composite. This work demonstrates a convenient, rapid, eco-friendly, and cost-effective method for synthesizing high-performance microwave absorption materials (MAMs).

Physical Activity Among Medical Students at the University of Khartoum, Sudan, 2022: Knowledge, Practice, and Barriers.

Introduction Physical inactivity is a highly prevalent modifiable risk factor for many diseases, including cardiovascular and cerebrovascular diseases, the leading causes of death. Many health institutes have issued and adopted guidelines and recommendations on physical activity. This study aims to study the knowledge, practice, and barriers of medical students enrolled at the University of Khartoum, Sudan, regarding physical activity. It aimed to assess the students' knowledge about physical activity, to determine the levels of physical activity and compare it with the WHO recommended levels and data from other countries, to compare the activity and sedentary levels between males and females, and to take a look on the barriers to physical activity. Methods An observational, descriptive, cross-sectional study was conducted at the Faculty of Medicine, University of Khartoum in December 2022. A total of 336 students were included using systematic random sampling. Data were collected using an online questionnaire that included the Global Physical Activity Questionnaire (GPAQ). Levels of physical activity were described and compared between males and females. Results Around 40.5% of the students achieved the recommended level of physical activity. The mean level of vigorous-intensity physical activity was 50.9 minutes/week (SD= 125.7), the mean level of moderate-intensity physical activity was 156.5 minutes/week (SD= 316.1), the mean level of total physical activity was 207 minutes/week (SD= 356). Between males and females, there was a significant mean difference in the level of vigorous-intensity physical activity and total physical activity. The mean level of sedentary behavior was 7.61 hours/day (SD= 4.62) with no significant difference between males and females (p=0.127). Students showed good knowledge about the cardiovascular and mental benefits of physical activity but not about its protective benefits against cancer. Only 19.4% knew the WHO-recommended levels of physical activity. The most common major barriers toward physical activity reported by the students were lack of time (43.8%), and lack of suitable facilities (31.3%) among others. Conclusion More than half (59.5%) of the students were insufficiently active. Levels of physical activity were significantly associated with the participants' sex but not their knowledge of the recommended levels of physical activity. Males showed higher levels of physical activity. Lack of time was the most common barrier to exercise. More knowledge and education about physical activity should be provided as well as suitable facilities.

Role of Resistin in Various Diseases with Special Emphasis on Periodontal and Periapical Inflammation - A Review.

Resistin is a small adipocyte-specific secretory hormone molecule. It has been associated with a number of cellular and metabolic processes. It has also been essentially implicated to have a vital role in the interplay between insulin resistance, obesity, and type II diabetes. Numerous clinical studies have demonstrated an association between many pathological illnesses with elevated serum resistin levels. It has also been shown to affect and modulate various molecular processes such as atherosclerosis, cancer cell metabolism, and inflammation. Periodontitis is a widespread inflammatory disease affecting human beings. Periapical periodontitis is an inflammatory disease that manifests as a sequela of untreated dental caries. Therefore, in this article, we summarize the divergent physiological roles played by resistin and its association with the mechanism of various pathologies. Moreover, current scientific studies discussing its association and role in common dental pathologies, periodontitis, and apical periodontitis are reviewed.

The Quality of Discharge Summaries at Al-Shaab Hospital, Sudan, in 2022: The First Cycle of a Clinical Audit.

Background The discharge summary is a vital component of the modern health system. It is defined as a synopsis of information regarding events occurring during the inpatient care of a patient, to allow for a safe, quick, and effective patient-centered discharge process. It contains important information about the patient's hospital stay, including the reason for admission, treatment received, and follow-up needed. Low-quality discharge summaries pose a great risk to patient healthcare since the most frequent reason for error in clinical settings is poor communication. In the United Kingdom, the Professional Record Standards Body (PRSB) has adopted the Academy of Medical Royal Colleges (AoMRC) "Standards for the Clinical Structure and Content of Patient Records" and produced a standard discharge summary form. This study aimed to assess the quality of discharge summaries at Al-Shaab Hospital in Sudan in terms of information, filling adequacy, and adherence to international guidelines and evaluate the discharge interviews. Methods A cross-sectional institution-based study was conducted in the period of September to December 2022 at Al-Shaab Teaching Hospital in Khartoum, Sudan. Systematic random sampling was used to select the study participants from the discharged patients. A total of 70 patients were met in their wards over a period of two months, and the contents of their discharge cards were compared to items on an online checklist based on the Professional Record Standards Body (PRSB) and the Academy of Medical Royal Colleges (AoMRC) standard discharge summary. The patients were also interviewed to assess their knowledge regarding their discharge information. Results The hospital's discharge summary form contained only four headings: date, patient name, age, and ID number. The assessed cards were found to be missing valuable information, including date of admission (missing in 83%), filling doctor's name (missing in 71%), and medication changes (missing in 70%). Only half of the summaries were clearly readable. The majority of patients had poor knowledge regarding their medication side effects (89%) and how to act in an emergency (86%), while knowledge of medication doses and follow-up details was good in 80% and 66%, respectively. Conclusion The patients are discharged with inadequately filled discharge forms. This may be due to the poor design of the form, so a newly designed form will be proposed, based on international standards. The discharge interview is also in need of improvement, to make sure patients are fully aware of their condition.

Endoscopic resection of superficial bowel neoplasia: The unmet needs in the Egyptian practice.

BACKGROUND: Management of superficial bowel neoplasia (SBN) in early stages is associated with better outcomes. The last few decades experienced a paradigm shift in the management of SBN with the introduction of advanced endoscopic resection techniques (ERTs). However, there are no clear data about the aspects of ERTs in Egypt despite the growing gastroenterology practice. AIM: To investigate the knowledge, attitude, and practice of ERTs toward management of SBN among Egyptian practitioners and the suitability of the endoscopy units' infrastructures toward these techniques. METHODS: An online 2-pages questionnaire was used. The first page comprised demographic data, and questions for all physicians, about the knowledge (11 questions) of and attitude (5 questions) toward ERTs as a therapeutic option for SBN. The second page investigated the practice of ERTs by endoscopists (6 questions) and the infrastructures of their endoscopy units (14 questions). The survey was disseminated through July 2021 and the data were collected in an excel sheet and later analyzed anonymously. RESULTS: The complete responses were 833/2300 (36.2%). The majority of the participants were males (n = 560, 67.2%), middle-aged (n = 366, 43.9%), consultants (n = 464, 55.7%), gastroenterologists (n = 678, 81.4%), spending ≥ 15 years in practice (n = 368, 44.2%), and were working in university hospitals (n = 569, 68.3%). The majority correctly identified the definition of SBN (88.4%) and the terms polypectomy, endoscopic mucosal resection (EMR), and endoscopic submucosal dissection (ESD) (92.1%, 90.2%, and 89.1% respectively). However, 26.9%, 43.2% and 49.5% did not recognize the clear indication of polypectomy, EMR, and ESD respectively. Although 68.1% of physicians are convinced about the ERTs for management of SBN; only 8.9% referred all candidate cases for ERTs. About 76.5% of endoscopists had formal training in the basic polypectomy techniques while formal training for EMR and ESD was encountered only in 31.9% and 7.2% respectively. About 71.6% and 88.4% of endoscopists did not perform EMR or ESD in the last one year. Consequently, the complication rate reported by endoscopists was limited to 18.1% (n = 103) of endoscopists. Only 25.8% of endoscopists feel confident in the management of ERTs-related complications and a half (49.9%) were not sure about their competency. Regarding the endoscopy units' infrastructures, only 4.2% of the centers had their endoscopes 100% armed with optical enhancements and 54.4% considered their institutions ready for managing ERTs-related complications. Only 18.3% (n = 104) of endoscopists treated their complicated cases surgically because the most frequent ERTs-related complications were procedural bleeding (26.7%), and perforations (17%). CONCLUSION: A significant deficiency was reported in the knowledge and attitude of Egyptian practitioners caring for patients with SBN toward ERTs. The lack of trained endoscopists in both EMR and ESD in part is due to unsuitable infrastructures of many endoscopy units.

Ultrasound-guided versus uterine sound-sparing approach during copper intrauterine device insertion: a randomised clinical trial.

OBJECTIVE: To compare the outcomes of trans-abdominal ultrasound (TAS) guided approach and uterine sound-sparing approach (USSA) during copper intrauterine device (IUD) insertion. STUDY DESIGN: A randomised open-label clinical trial (Clinical Trials.Gov: NCT03383432) included multiparous women requesting Copper IUD insertion for birth control were invited to participate. The eligible women were randomised into two groups (44 women in each group); group I (TAS-guided IUD insertion) and group II: USSA. The primary outcome was to measure the satisfaction score of IUD insertion in both methods. Secondary outcomes included the easiness score (ES), the difference in pain scores during IUD insertion, the duration of insertion, and the successful device placement after one week and one month evaluated by transvaginal ultrasound (TVS). RESULTS: Eighty-eight women were analysed in both groups. The VAS for satisfaction was significantly higher in the USSA group than the TAS-guided group (7.80 ± 1.27 vs. 5.45 ± 1.42, p = .0001). There was significantly lower VAS of pain scores during IUD insertion in the USSA group as compared with the TAS-guided IUD (p = .001). A lower ES and a significantly shorter duration of IUD insertion were also determined among the USSA group (p = .0001). CONCLUSIONS: USSA is associated with higher satisfaction and less pain during insertion than the TAS-guided IUD insertion approach. However, both techniques have optimal intra-uterine device positioning.

From Muscles to Wires: Report of Two Cases and Literature Review on COVID-19 Vaccination and Cardiac Conduction Disturbance.

Since the end of 2020, several vaccines have become available as part of the global efforts to contain the adverse health outcomes of the coronavirus disease 2019 (COVID-19) pandemic. Although research has confirmed their safety on large scales, several post-marketing reports have revealed some rare cardiovascular side effects. Towards the end of the first half of 2021, multiple reports indicate possible links between COVID-19 vaccines (both mRNA-based vaccine and vector-based vaccines) and myopericarditis. Nevertheless, cardiac conduction disease in this context has only rarely been reported. In this report, we present two cases of probable vaccination-induced cardiac conduction disturbances along with a thorough literature review. In addition, we discuss probable pathophysiological mechanisms and insights into the suggested areas for future research. To our knowledge, these are the first published cases to result in permanent pacemaker implantation.

A comparative study of polydioxanone (PDS) and polyglactin (Vicryl) in hypospadias repair.

BACKGROUND: Hypospadias is a fairly common problem, and it is the most common genital congenital anomaly. OBJECTIVE: This study was carried out to compare polyglactin and polydioxanone in hypospadias repair by assessing the rate of complications, especially urethrocutaneous fistula (UCF) formation. PATIENTS AND METHODS: This is a prospective observational cross-sectional hospital-based study carried out at the Department of Paediatric Surgery, Ribat University Hospital, from June 2015 to November 2016. In Group A, there were 55 patients who underwent repair using polyglactin, and in Group B, there were 50 patients who underwent repair using polydioxanone. All patients were operated by the same surgeon. RESULTS: The mean age of Group A was 5.7 ± 4.3 years and 5.1 ± 3.9 years in Group B. Meatal advancement and glanuloplasty incorporated operation was done in 47.6%, Tubularized incised plate urethroplasty in (31.4%), Theirsch-Duplay in 20% and Mathieu's repair in 1%. The complication rate was 34% in Group A and 10.9% in Group B. The most frequent complication was UCF, as 19 patients (18.1%) of the study candidates developed UCF; most of them were in Group A (14 patients) and 5 patients in Group B. Another significant complication was meatal stenosis, which occurred in 11 patients (10.5%): 9 in Group A and 2 in Group B. CONCLUSION: Polydioxanone (PDS) is satisfactory in hypospadias repair as it is associated with better outcome, especially UCF, which is most common and most difficult to treat complication.

Ancient foe, serious weapon: Subarachnoid hemorrhage secondary to TB meningitis.

Tuberculosis is an ancient infectious disease with global distribution and a multitude of multisystem presentations. Infection of the central nervous system (CNS) is the most serious presentation manifested as tuberculous meningitis (TBM), intracranial tuberculoma, and tuberculous arachnoiditis all associated with significant morbidity and mortality. TBM is the commonest form of CNS manifestations capable of causing secondary arteritis leading to vascular complications. We report a case of a 22-year-old Indian patient diagnosed with TBM who subsequently presented with sudden onset severe headache, which was eventually diagnosed as subarachnoid hemorrhage. Radiological assessment confirmed secondary complications with cerebral aneurysmal dilatation attributed to TBM. The patient was safely managed with combined radiological and surgical interventions with uneventful outcomes. Review of the literature revealed that such complication of TBM is rare usually with serious implications. We aim to highlight to infection specialists to be aware of such association.

Hyperthyroidism as a Precipitant Factor for Cerebral Venous Thrombosis: A Case Report.

Cerebral venous sinus thrombosis (CVT) is an uncommon yet serious condition. While CVT has many known precipitants and etiologies, hyperthyroidism as a precipitant of CVT is not well understood. This study reported a case of a 41-year-old male with a 4-year history of hyperthyroidism presented with seizure. Consequently, a diagnosis of superior sagittal sinus thrombosis was confirmed by computed tomography and magnetic resonance (MR) venograms. Extensive investigations yielded no apparent underlying cause, but laboratory findings were consistent with uncontrolled hyperthyroidism. The patient improved rapidly following anticoagulation. Follow-up MR and MRV scans 2 months after treatment revealed full recanalization of the superior sagittal sinus. This case report highlighted hyperthyroidism, as a procoagulant condition, resulting specifically in superior sagittal sinus thrombosis.

Highly Flexible, Efficient, and Sandwich-Structured Infrared Radiation Heating Fabric.

Controlling thermal energy is one of the biggest concerns along with the progress of human civilization for thousands of years. Current thermal comfort devices are mainly based on materials that are bulky, rigid, and heavy, largely limiting their widespread practical applications. It still remains a challenge to develop highly lightweight, flexible, and efficient electrical heaters for personal thermal management and local climate control. In this work, we present a high-performance composite infrared radiation heating fabric (IRHF), which mainly consists of two layers of poly(ethylene terephthalate) (PET) fabrics and one sandwiched layer of carbon nanofibers embedded with different inorganic nanoparticles. A copper electrode sheet was connected with the carbon nanofibers to form a conductive heating circuit. The permanent spontaneous polarization of both carbon nanofibers and infrared radiation nanoparticles can facilitate an enhanced current in the heater by creating an additional electrical field, which results in a fast electrothermal response and favorable heat preservation. The constructed IRHF could achieve an increase in the temperature to 43 °C from room temperature in 1 min under a voltage of 30 V, with an electrothermal conversion efficiency up to 78.99%. With a collection of compelling features such as good thermal stability, excellent flexibility and breathability, and high electrical conductivity and energy conversion efficiency, the fabricated sandwich-structured IRHF can open up new opportunities to develop smart heating textiles and wearable heating clothes in many fields.

A randomized trial comparing the efficacy and safety of treating patients with type 2 diabetes and highly elevated HbA1c levels with basal-bolus insulin or a glucagon-like peptide-1 receptor agonist plus basal insulin: The SIMPLE study.

AIM: To compare the efficacy and safety of a glucagon-like peptide-1 receptor agonist (GLP1RA) plus basal insulin versus basal-bolus insulin treatment in patients with very uncontrolled type 2 diabetes. MATERIALS AND METHODS: The SIMPLE study was a 6-month pragmatic, randomized, open-label trial testing the effectiveness of two approaches to treat patients with type 2 diabetes and HbA1c ≥10%. We randomized patients to detemir plus liraglutide or detemir plus aspart (before each meal). The primary endpoint was change in HbA1c; changes in body weight, insulin dose, hypoglycaemia and diabetes-related quality-of-life were secondary outcomes. RESULTS: We randomized 120 participants aged 47.4 ± 9.5 years, Hispanic 40%, African American 42%, diabetes duration 10 [25th-75th percentile (6 to 15)] years, body mass index 37.2 ± 10.3 kg/m2 . HbA1c decreased more with GLP1RA plus basal insulin [12.2% (95% CI 11.8% to 12.6%) to 8.1% (95% CI 7.4% to 8.7%)] compared with basal-bolus insulin [11.8% (95% CI 11.5% to 12.2%) to 8.8% (95% CI 88.1% to 9.55%)]; estimated treatment difference (ETD) of -1.1% (95% CI -2.0% to -0.1%) (non-inferiority margin 0.4% and P = .0001, superiority P = .026). Compared with basal-bolus insulin, treatment with GLP1RA plus basal insulin led to a body weight ETD of -3.7 kg (95% CI -5.8 to -1.5; P = .001), fewer patients experiencing hypoglycaemia [66.1% vs 35.2% (P = .002)], and greater improvements in general/current health perception, treatment satisfaction, and fear of hypoglycaemia, while taking a lower total daily dose of insulin [estimated treatment ratio 0.68 (95% CI 0.55 to 0.84)]. CONCLUSIONS: In patients with HbA1c ≥10% treatment with GLP1RA plus basal insulin, compared with basal-bolus insulin, resulted in better glycaemic control and body weight, lower insulin dosage and hypoglycaemia, and improved quality of life. This treatment strategy is an effective and safe alternative to a basal-bolus insulin regimen.

Breaking bad news from the doctors' perspective in a paternalistic society: the case of Sudan.

Breaking bad news is a global challenge for all types of health providers. Our study assessed the attitude and practice from the doctors' perspective in a patriarchal society. A descriptive cross-sectional hospital-based study was conducted, involving doctors from both medical and surgical departments. Almost half of the respondents believed that Sudanese patients do not like to know their diagnosis, and a slightly higher proportion had no previous training on how to break bad news. Some 20% indicated that they would conceal the diagnosis from a patient if his or her relatives so requested. Less than one-quarter of respondents followed a standard protocol. Although most of the doctors subscribed to the notion that patients have the right to know everything about their illnesses, not all of them held this attitude towards their local patient population.

EBV Associated Breast Cancer Whole Methylome Analysis Reveals Viral and Developmental Enriched Pathways.

Background: Breast cancer (BC) ranks among the most common cancers in Sudan and worldwide with hefty toll on female health and human resources. Recent studies have uncovered a common BC signature characterized by low frequency of oncogenic mutations and high frequency of epigenetic silencing of major BC tumor suppressor genes. Therefore, we conducted a pilot genome-wide methylome study to characterize aberrant DNA methylation in breast cancer. Results: Differential methylation analysis between primary tumor samples and normal samples from healthy adjacent tissues yielded 20,188 differentially methylated positions (DMPs), which is further divided into 13,633 hypermethylated sites corresponding to 5339 genes and 6,555 hypomethylated sites corresponding to 2811 genes. Moreover, bioinformatics analysis revealed epigenetic dysregulation of major developmental pathways including hippo signaling pathway. We also uncovered many clues to a possible role for EBV infection in BC. Conclusion: Our results clearly show the utility of epigenetic assays in interrogating breast cancer tumorigenesis, and pinpointing specific developmental and viral pathways dysregulation that might serve as potential biomarkers or targets for therapeutic interventions.

Association of Epstein - Barr virus and breast cancer in Eritrea.

BACKGROUND: The oncogenic potential of Epstein-Barr virus (EBV) in breast cancer is being increasingly recognized. Despite some controversies regarding such role, new evidence is suggesting a culpability of EBV in breast cancer, particularly in Africa where the virus has been originally associated with causation of several solid and hematological malignancies. One example is a report from Sudan implicating EBV as a prime etiologic agent for an aggressive type of breast cancer, where nearly 100% of tumor tissues were shown to carry viral signatures. To get a broader view on such association, other nearby countries should be investigated. The present study aims to determine the prevalence and possible associations of the virus in Eritrean breast cancer patients. METHODS: Detection of EBV genome using primers that target Epstein Barr Encoded RNA (EBER) gene and Latent Membrane Protein-1 (LMP-1) gene sequences was performed by polymerase chain reaction (PCR) on DNA samples extracted from 144 formalin fixed paraffin embedded breast cancer tissues and 63 non-cancerous breast tissue as control group. A subset of PCR positive samples was evaluated for EBER gene expression by in situ hybridization (ISH). Expression of Latent Membrane Protein-2a (LMP2a) was also assessed by immunohistochemistry in a subset of 45 samples. RESULTS: Based on PCR results, EBV genome signals were detected in a total of 40 samples (27.77%) as compared to controls (p-value = 0. 0031) with a higher sensitivity when using the EBER primers. Five out of the 14 samples stained by EBER-ISH 35.71% were positive for the virus indicating the presence of the viral genome within the tumor cells. Of those stained for IHC 7 (15.55%) were positive for LMP2a showing low viral protein frequency. CONCLUSIONS: Based on these findings it can be concluded that EBV in Eritrea is associated with a smaller subset of tumors, unlike neighboring Sudan, thus pointing to possible differences in population predisposition and diseases epidemiology.

Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways.

The molecular basis of cancer and cancer multiple phenotypes are not yet fully understood. Next Generation Sequencing promises new insight into the role of genetic interactions in shaping the complexity of cancer. Aiming to outline the differences in mutation patterns between familial colorectal cancer cases and controls we analyzed whole exomes of cancer tissues and control samples from an extended colorectal cancer pedigree, providing one of the first data sets of exome sequencing of cancer in an African population against a background of large effective size typically with excess of variants. Tumors showed hMSH2 loss of function SNV consistent with Lynch syndrome. Sets of genes harboring insertions-deletions in tumor tissues revealed, however, significant GO enrichment, a feature that was not seen in control samples, suggesting that ordered insertions-deletions are central to tumorigenesis in this type of cancer. Network analysis identified multiple hub genes of centrality. ELAVL1/HuR showed remarkable centrality, interacting specially with genes harboring non-synonymous SNVs thus reinforcing the proposition of targeted mutagenesis in cancer pathways. A likely explanation to such mutation pattern is DNA/RNA editing, suggested here by nucleotide transition-to-transversion ratio that significantly departed from expected values (p-value 5e-6). NFKB1 also showed significant centrality along with ELAVL1, raising the suspicion of viral etiology given the known interaction between oncogenic viruses and these proteins.

Microscopic polyangiitis causing diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis.

Diffuse alveolar hemorrhage complicating small vessel vasculitis is a life-threatening emergency and should be considered in the differential diagnosis of patients who develop rapidly progressive dyspnea with alveolar opacities on chest imaging. In these patients, the coexistence of pulmonary and renal involvement suggests a multisystem disease. We present a case of a man who presented to our hospital with diffuse alveolar hemorrhage, severe anemia, and rapidly progressive glomerulonephritis.

Genetic determinants of anti-malarial acquired immunity in a large multi-centre study.

BACKGROUND: Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. METHODS: Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. RESULTS: Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. CONCLUSION: Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity.

Insights into the possible role of IFNG and IFNGR1 in Kala-azar and Post Kala-azar Dermal Leishmaniasis in Sudanese patients.

BACKGROUND: Little is known about the parasite/host factors that lead to Post Kala-azar Dermal Leishmaniasis (PKDL) in some visceral leishmaniasis (VL) patients after drug-cure. Studies in Sudan provide evidence for association between polymorphisms in the gene (IFNGR1) encoding the alpha chain of interferon-γ receptor type I and risk of PKDL. This study aimed to identify putative functional polymorphisms in the IFNGR1 gene, and to determine whether differences in expression of interferon-γ (IFNG) and IFNGR1 at the RNA level are associated with pathogenesis of VL and/or PKDL in Sudan. METHODS: Sanger sequencing was used to re-sequence 841 bp of upstream, exon1 and intron1 of the IFNGR1 gene in DNA from 30 PKDL patients. LAGAN and SYNPLOT bioinformatics tools were used to compare human, chimpanzee and dog sequences to identify conserved noncoding sequences carrying putative regulatory elements. The relative expression of IFNG and IFNGR1 in paired pre- and post-treatment RNA samples from the lymph nodes of 24 VL patients, and in RNA samples from skin biopsies of 19 PKDL patients, was measured using real time PCR. Pre- versus post-treatment expression was evaluated statistically using the nonparametric Wilcoxon matched pairs signed-rank test. RESULTS: Ten variants were identified in the 841 bp of sequence, four of which are novel polymorphisms at -77A/G, +10 C/T, +18C/T and +91G/T relative to the IFNGR1 initiation site. A cluster of conserved non-coding sequences with putative regulatory variants was identified in the distal promoter of IFNGR1. Variable expression of IFNG was detected in lymph node aspirates of VL patients before treatment, with a marked reduction (P = 0.006) in expression following treatment. IFNGR1 expression was also variable in lymph node aspirates from VL patients, with no significant reduction in expression with treatment. IFNG expression was undetectable in the skin biopsies of PKDL cases, while IFNGR1 expression was also uniformly low. CONCLUSIONS: Uniformly low expression of IFN and IFNGR1 in PKDL skin biopsies could explain parasite persistence and is consistent with prior demonstration of genetic association with IFNGR1 polymorphisms. Identification of novel potentially functional rare variants at IFNGR1 makes an important general contribution to knowledge of rare variants of potential relevance in this Sudanese population.