Mesenchymal Stem Cells Modulate SIRT1/MiR-134/ GSK3ß Signaling Pathway in a Rat Model of Alzheimer's Disease.

Prolonged exposure to environmental aluminum-containing substances is associated with the development of Alzheimer's disease (AD). AD is a brain disorder associated with a gradual weakening in neurocognitive functions. Mesenchymal stem cells (MSCs) transplant as a promising and safe approach is used to treat AD through countless mechanisms. Therefore, this study aims to elucidate how MSCs improve biochemical and histopathological approaches associated with the AD model in rats. MSCs treatment restores the redox status impairment through a notable decline in the malondialdehyde (MDA) levels along with antioxidant enrichment. The anti-inflammatory effect of MSCs through conversion of microglial cells from M1 to M2 and inhibition of pro-inflammatory mediator's release work in with de-activated GSK-3ß. Additionally, the alleviation of autophagy and lysosomal clearance of Aß and tau aggregates was accompanied by a down-regulation of the mTOR. Moreover, MSCs upregulate the expression of SIRT1 together with a limited expression of miR-134 thereby, improve neurite outgrowth and synaptic loss. Overall, the obtained data confirm the novelty of MSCs in the treatment of AD not only by their antioxidant, anti-inflammatory effect but also by restoring the neural integrity, neurogenesis, improving the neurocognitive function, and modulation of the signal pathways linked to the Aß hypothesis.

Genetic variants of APEX1 p.Asp148Glu and XRCC1 p.Gln399Arg with the susceptibility of hepatocellular carcinoma.

The DNA repair genes have a crucial function in the base excision repair (BER) mechanism among different cancerous disorders, particularly hepatocellular carcinoma (HCC). The foremost objective of this study is to explore the association of genetic variants of the APEX1 p.Asp148Glu and the XRCC1 p.Gln399Arg with the susceptibility of HCC and to identify the computational bioinformatics frameworks of these missense variants. A total of 250 participants were enrolled in this study, including 150 HCC patients and 100 cancer-free controls. The genomic DNA was characterized and genotyped by applying the PCR-CTPP method. The frequency of the APEX1 (rs1130409*Glu) allele was statistically significant with increased risk of HCC (OR = 1.66, 95% CI = 1.12-2.45), while the XRCC1 (rs25487*Gln) allele conferred a protection against the progression of HCC (OR = 0.64, 95% CI = 0.42-0.96). Furthermore, HCC patients carrying the APEX1 p.Asp148Glu and the XRCC1 p.Gln399Arg variants indicated no significant difference with the clinical, and laboratory parameters (p > .05). Our findings confirmed that the APEX1 p.Asp148Glu variant was associated with increased risk of HCC, while the XRCC1 p.Gln399Arg variant revealed protection against the development of HCC.

New insights inside the interdigitating dendritic cell sarcoma-pooled analysis and review of literature.

Interdigitating dendritic cell sarcoma is a rare haematological neoplasm with high debatable management protocols. The data extracted from 127 case reports published between 1981 and 2018 were analysed. The median age at diagnosis was 58 years with a male to female ratio of 1.65:1. The median OS and PFS of IDCS were 12 and 6 months, respectively, with a disease-specific mortality rate of 36.4%. Two-thirds of patients had a localised disease, while 30% had a disseminated form with 1-year mortality rates of 21.1% and 78.9%, respectively. Twenty per cent of cases were associated with other malignancies. Histologically, the proliferation of large spindle-shaped cells with fascicular growth was described in 84.3% of cases. Based on Cox-regression model, surgical resection was the only treatment modality linked to survival improvement with no recorded survival benefits of radiotherapy and chemotherapy. The 1-year mortality rates in resected and non-resected disease were 17.8% and 63.2%, respectively (P < 0.0001).

Decision Support System for Lymphoma Classification.

The diffuse lymphoma is a malignant tumor of lymphoid tissues. It is associated with abnormal, unlimited and uncontrolled proliferation of lymphoid cells. Until now, expert pathologists have identified diffuse lymphoma cells disease manually. This paper introduces automatic system with a friendly user interface to differentiate between the categories of the diffuse lymphoma cells. This research is based on the morphological features such as size, perimeter and circularity. The cell size is a critical element in the classification of diffuse lymphoma according to international formulation standards. Therefore, the applied procedures identify lymphoid cell population in digital microscopic images. The cells are classified using their morphological data according to the characteristics of each cell such as: circularity, perimeter, area, and color density. The number of cells is taken into consideration in the developed approach. Image processing techniques are applied to digital microscopic images to measure morphological parameters and to overcome image problems such as overlapping and cell distortion that affect the sensitivity of the measured data. The developed procedures help the pathologists to come to a decision regarding the classification of diffuse lymphoma. Moreover, it can be used to train medical students and young pathologists.

Frequency of intestinal parasites among food-handlers in Khartoum, Sudan.

Food-handlers (n = 1500) attending the public health laboratory in Khartoum, Sudan, for annual check-ups were screened for intestinal parasites by 3 different techniques (direct faecal examination, formol-ether concentration and floatation) to evaluate the adequacy of annual screening. Results showed that 29.4% of food-handlers were harbouring intestinal protozoa in stool samples: Entamoeba coli in 15.3%, Giardia lamblia in 9.7%, and Enta. histolytica in 4.3%. Moreover, 2.7% of food-handlers harboured intestinal helminths: Hymenolepis nana (1.6%), Schistosoma mansoni (0.7%), Taenia saginata (0.3%) and Strongyloides stercoralis (0.1%). We recommend more frequent screening of food-handlers and that the direct faecal smear technique is efficient for the detection of such parasites.

Frequency of intestinal parasites among food-handlers in Khartoum, Sudan

Food-handlers [n = 1500] attending the public health laboratory in Khartoum, Sudan, for annual check-ups were screened for intestinal parasites by 3 different techniques [direct faecal examination, formol-ether concentration and floatation] to evaluate the adequacy of annual screening. Results showed that 29.4% of food-handlers were harbouring intestinal protozoa in stool samples: Entamoeba coli in 15.3%, Giardia lamblia in 9.7%, and Enta. histolytica in 4.3%. Moreover, 2.7% of food-handlers harboured intestinal helminths: Hymenolepis nana [1.6%], Schistosoma mansoni [0.7%], Taenia saginata [0.3%] and Strongyloides stercoralis [0.1%]. We recommend more frequent screening of food-handlers and that the direct faecal smear technique is efficient for the detection of such parasites

Synthesis and antiviral evaluation of novel 2,3-dihydroxypropyl nucleosides from 2- and 4-thiouracils.

Regioselective alkylation of 2-thiouracils 1a-c and 4-thiouracils 7a,b with 2,3-O-isopropylidene-2,3-dihydroxypropyl chloride (2) afforded 2-[[(2,2-Dimethyl-1,3-dioxolan-4-yl) methyl]thio]pyrimidin-4(1H)-ones 3a-c and 4-[[(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl]thio] pyrimidin-2(1H)-ones 8a,b, respectively. Further alkylation with 2 and/or 2,3-O-isopropylidine-1-O-(4-toluenesulfonyl)-glycerol (4) gave the acyclo N-nucleosides 5a-c and 9a,b whose deprotection afforded 6a-c and 10a,b. 2-(Methylthio)pyrimidin-4(1H)-ones 11a-c and 4-(methylthio)pyrimidin-2(1H)-ones 14a,b were treated with 2 and/or 4 to give 12a-c and 15a,b which were deprotected to give 13a-c and 16a,b. Pyrimidine-2,4(1H,3H)-dithiones 17a-c were treated with two equivalents of 2 to give 2,4-bis[[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]thio] pyrimidines 18a-c. Deprotection of compounds 18a-c gave 2,4-bis[(2,3-dihydroxypropyl)thio]pyrimidines 19a-c. The activity of the deprotected nucleosides against Hepatitis B virus was evaluated and showed moderate inhibition activity against HBV with mild cytotoxicity.

From chloroquine to artemisinin-based combination therapy: the Sudanese experience.

BACKGROUND: In Sudan, chloroquine (CQ) remains the most frequently used drug for falciparum malaria for more than 40 years. The change to artemisinin-based combination therapy (ACT) was initiated in 2004 using the co-blister of artesunate + sulfadoxine/pyrimethamine (AS+SP) and artemether + lumefantrine (ART+LUM), as first- and second-line, respectively. This article describes the evidence-base, the process for policy change and it reflects the experience of one year implementation. Relevant published and unpublished documents were reviewed. Data and information obtained were compiled into a structured format. CASE DESCRIPTION: Sudan has used evidence to update its malaria treatment to ACTs. The country moved without interim period and proceeded with country-wide implementation instead of a phased introduction of the new policy. The involvement of care providers and key stakeholders in a form of a technical advisory committee is considered the key issue in the process. Development and distribution of guidelines, training of care providers, communication to the public and provision of drugs were given great consideration. To ensure presence of high quality drugs, a system for post-marketing drugs surveillance was established. Currently, ACTs are chargeable and chiefly available in urban areas. With the input from the Global Fund to fight AIDs, Tuberculosis and Malaria, AS+SP is now available free of charge in 10 states. CONCLUSION: Implementation of the new policy is affected by the limited availability of the drugs, their high cost and limited pre-qualified manufacturers. Substantial funding needs to be mobilized by all partners to increase patients' access for this life-saving intervention.

The Efficacy of Artemether/Lumefantrine for the Treatment of Uncomplicated Falciparum Malaria in Children in an Area of High Transmission in Southern Sudan

"Objectives: Sudanese health authority adopted a new antimalarial drug policy in response to the reported high level of chloroquine resistance. ""Artesunate+ sulfadoxine/pyrimethamine"" (ASP) and ""artemether/lumefantrine"" (A/L) are recommended as first and second lines for the treatment of uncomplicated falciparum malaria respectively. This study aims to evaluate the clinical and parasitological response to A/L and to report any side effects related to the drug in children living in high transmission areas. Methods: This evaluation of the clinical and parasitological response to directly observed treatment with 6 doses A/L following WHO protocol for monitoring antimalarial drugs efficacy. Giemsa-stained thick and thin blood smears were examined microscopically. Results: A total of 75 (40.8) patients met the inclusion criteria; of them 70 (97.2) patients showed adequate clinical and parasitological response (radical cure); 2 (2.8) patients were classified as early treatment failure and 3 (4) patients were lost to be followed-up by day 3. No progression to severe illness or danger signs occurred for any patient during the study. Conclusion: The main outcome of study was that A/L was found to be highly effective against Plasmodium falciparum uncomplicated malaria; well tolerated by children with no reported serious side effects. Dramatic decrease in parasites density and fever were observed in most of the cases by day 3 of treatment."

Clinical and laboratory aspects of malaria among children with fever in a low transmission area of Sudan.

A cross-sectional study explored the clinical and laboratory aspects of malaria among children presenting with fever to 2 paediatric hospitals in Khartoum state during the low transmission season. Out of 655 febrile patients, 35.9% were recorded as having malaria based on hospital laboratory results. However, re-examination of slides at the National Malaria Control Programme referral laboratory confirmed malaria in only 32.8% of those diagnosed with malaria at hospital level. Analysis of symptoms and signs revealed great variability in clinical presentation. Although some findings were associated with malaria, developing a sensitive clinical algorithm was difficult. Further investment is needed to improve microscopic diagnosis facilities in local hospitals to overcome the problem of over-diagnosis of malaria.

Clinical and laboratory aspects of malaria among children with fever in a low transmission area of Sudan

A cross-sectional study explored the clinical and laboratory aspects of malaria among children presenting with fever to 2 paediatric hospitals in Khartoum state during the low transmission season. Out of 655 febrile patients, 35.9% were recorded as having malaria based on hospital laboratory results. However, re-examination of slides at the National Malaria Control Programme referral laboratory confirmed malaria in only 32.8% of those diagnosed with malaria at hospital level. Analysis of symptoms and signs revealed great variability in clinical presentation. Although some findings were associated with malaria, developing a sensitive clinical algorithm was difficult. Further investment is needed to improve microscopic diagnosis facilities in local hospitals to overcome the problem of over-diagnosis of malaria

A retrospective hospital study of human cystic echinococcosis in Egypt.

We performed a retrospective study to determine annual clinical incidence of human cystic echinococcosis (CE) in 14 Egyptian hospitals between January 1997 and December 1999. From 492 353 records examined, 133 (0.027%) new human CE cases were recorded. Of these, 50 (37.6%) were from Alexandria and Matrouh hospitals, 33 (24.8%) from Giza Chest Hospital and 50 from other regions. Matrouh governorate had the highest annual clinical incidence (1.34-2.60 per 100 000) followed by Giza governorate (0.80-1.16 per 100 000). About a third of those affected were aged < or = 20 years. Liver and lungs were the organs most affected. Although human CE is of low endemicity in Egypt, it may-represent a public health concern in Matrouh and Giza governorates.

A retrospective hospital study of human cystic echinococcosis in Egypt

We performed a retrospective study to determine annual clinical incidence of human cystic echinococcosis [CE] in 14 Egyptian hospitals between January 1997 and December 1999. From 492 353 records examined, 133 [0.027%] new human CE cases were recorded. Of these, 50 [37.6%] were from Alexandria and Matrouh hospitals, 33 [24.8%] from Giza Chest Hospital and 50 from other regions. Matrouh governorate had the highest annual clinical incidence [1.34-2.60 per 100 000] followed by Giza governorate [0.80-1.16 per 100 000]. About a third of those affected were aged </= 20 years. Liver and lungs were the organs most affected. Although human CE is of low endemicity in Egypt, it may-represent a public health concern in Matrouh and Giza governorates

Synthesis and anti-HBV activity of thiouracils linked via S and N-1 to the 5-position of methyl beta-D-ribofuranoside.

Reverse nucleoside derivatives of 2-(methylsulfanyl)uracils 6a-d were prepared by treating of the sodium salt of 2-(methylsulfanyl)uracils (5a-d) with methyl 2,3-O-isopropylidene-5-O-p-toluenesulfonyl-beta-D-ribofuranoside (2). The alkylation of 2-thiouracils 4a-d with methyl 5-deoxy-5-iodo-2,3-O-isopropylidene-D-ribofuranoside (3) afforded the corresponding S-ribofuranoside derivatives 8a-d. Deisopropylidenation of 6a-d and 8a-d afforded the corresponding deprotected derivatives 7a-d and 9a-d, respectively. The Anti-HBV activity of selected compounds was studied.

Nucleic acid component analogues: synthesis of 2'-deoxynucleosides from 5-substituted-4-hydroxy-6(1H)-pyrimidinones.

Condensation of the silylated pyrimidines 5a-c with methyl 2-deoxy-3,5-di-O-toluoyl-D-pentofuranoside 6, using trimethylsilyltriflate as catalyst gave anomeric mixtures of 2'-deoxynucleosides 7a-c, the pure alpha- and beta-anomers were separated and deprotected with sodium methoxide in methanol to give 1-(2'-deoxy-alpha-D-pentafuranosyl)-4-hydroxy-5-substituted-6(1H)-pyrimidinones 10a,b and 13a and their corresponding beta-anomers 11a,b and 13b.

Stratification of Khartoum urban area by the risk of malaria transmission.

A cross-sectional community-based study was carried out in Khartoum urban area aimed at stratifying the area by risk of malaria transmission. Two thousand households (8092 individuals) were surveyed during the cold, dry and rainy seasons of 2002. Households with screened windows, using bednets or both were 5.0% (95% CI: 4.1-6.0), 10.9% (95% CI: 9.5-12.3) and 1.8% (95% CI: 1.2-2.5) respectively. Access to health services was high. Only 3.8% (95% CI: 2.9-4.7) of households kept antimalarial drugs at home. The parasite rate, spleen rate and fever rate were very low (0.21%, 0.17% and 0.97% respectively). Overall, people in Greater Bahry suffer a greater burden of malaria than those in Greater Khartoum or Greater Omdurman, with a seasonal pattern of transmission.

Determinants of acquiring malaria among displaced people in Khartoum state, Sudan.

A cross-sectional descriptive study was carried out among displaced people in Khartoum state to determine risk factors associated with malaria. Data were collected from 856 households about sociodemographic characteristics, history of malaria, and knowledge, attitudes and treatment-seeking behaviour. Overall, 68.2% reported a malaria attack among household members in the previous year. Risk of malaria attack was significantly associated with tribe, language, education, water supply and food expenditure. The highest rates of attack were among local language speakers (85.5%) and illiterate residents (70.4%). Half the respondents (50.2%) delayed seeking treatment for malaria. Knowledge, attitudes and practices had no association with malaria attacks, except for a 4.7-fold increased risk of malaria when obtaining water from carts rather than wells.

Determinants of malaria mortality among displaced people in Khartoum state, Sudan.

To find the determinants of malaria mortality among displaced people, across-sectional descriptive study using verbal autopsy was carried out in 2 camps in Khartoum state, Sudan. The heads of 856 households were interviewed about household characteristics, and malaria knowledge, attitudes and behaviour. They reported 81 malaria deaths during the previous year, 3.5% of all household members; 70 (86.4%) were children. Fever, diarrhoea, vomiting and headache were the most prevalent symptoms before death. Having a malaria death in the household was significantly associated with poor knowledge about malaria and, surprisingly, with better education. Poor treatment-seeking behaviour and poor attitudes towards malaria were not associated with higher mortality. However, mortality was significantly higher among households obtaining water by cart than from a well.

Determinants of malaria mortality among displaced people in Khartoum state, Sudan

To find the determinants of malaria mortality among displaced people, across-sectional descriptive study using verbal autopsy was carried out in 2 camps in Khartoum state, Sudan. The heads of 856 households were interviewed about household characteristics, and malaria knowledge, attitudes and behaviour. They reported 81 malaria deaths during the previous year, 3.5% of all household members; 70 [86.4%] were children. Fever, diarrhoea, vomiting and headache were the most prevalent symptoms before death. Having a malaria death in the household was significantly associated with poor knowledge about malaria and, surprisingly, with better education. Poor treatment-seeking behaviour and poor attitudes towards malaria were not associated with higher mortality. However, mortality was significantly higher among households obtaining water by cart than from a well

Determinants of acquiring malaria among displaced people in Khartoum state, Sudan

A cross-sectional descriptive study was carried out among displaced people in Khartoum state to determine risk factors associated with malaria. Data were collected from 856 households about sociodemographic characteristics, history of malaria, and knowledge, attitudes and treatment-seeking behaviour. Overall, 68.2% reported a malaria attack among household members in the previous year. Risk of malaria attack was significantly associated with tribe, language, education, water supply and food expenditure. The highest rates of attack were among local language speakers [85.5%] and illiterate residents [70.4%]. Half the respondents [50.2%] delayed seeking treatment for malaria. Knowledge, attitudes and practices had no association with malaria attacks, except for a 4.7-fold increased risk of malaria when obtaining water from carts rather than wells