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1.
Nano Lett ; 24(28): 8465-8471, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38976772

RESUMO

The mechanical and thermal properties of transition metal dichalcogenides (TMDs) are directly relevant to their applications in electronics, thermoelectric devices, and heat management systems. In this study, we use a machine learning (ML) approach to parametrize molecular dynamics (MD) force fields to predict the mechanical and thermal transport properties of a library of monolayered TMDs (MoS2, MoTe2, WSe2, WS2, and ReS2). The ML-trained force fields were then employed in equilibrium MD simulations to calculate the lattice thermal conductivities of the foregoing TMDs and to investigate how they are affected by small and large mechanical strains. Furthermore, using nonequilibrium MD, we studied thermal transport across grain boundaries. The presented approach provides a fast albeit accurate methodology to compute both mechanical and thermal properties of TMDs, especially for relatively large systems and spatially complex structures, where density functional theory computational cost is prohibitive.

2.
Malar J ; 20(1): 436, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758827

RESUMO

BACKGROUND: The currently used malaria vaccine, RTS,S, is designed based on the Plasmodium falciparum circumsporozoite protein (PfCSP). The pfcsp gene, besides having different polymorphic patterns, can vary between P. falciparum isolates due to geographical origin and host immune response. Such aspects are essential when considering the deployment of the RTS,S vaccine in a certain region. Therefore, this study assessed the genetic diversity of P. falciparum in Sudan based on the pfcsp gene by investigating the diversity at the N-terminal, central repeat, and the C-terminal regions. METHODS: A cross-sectional molecular study was conducted; P. falciparum isolates were collected from different health centres in Khartoum State between January and December 2019. During the study period, a total of 261 febrile patients were recruited. Malaria diagnosis was made by expert microscopists using Giemsa-stained thick and thin blood films. DNA samples were examined by the semi-nested polymerase chain reaction (PCR). Single clonal infection of the confirmed P. falciparum cases, were used to amplify the pfcsp gene. The amplified amplicons of pfcsp have been sequenced using the Sanger dideoxy method. The obtained sequences of pfcsp nucleotide diversity parameters including the numbers of haplotypes (Hap), haplotypes diversity (Hapd), the average number of nucleotide differences between two sequences (p), and the numbers of segregating sites (S) were obtained. The haplotype networks were constructed using the online tcsBU software. Natural selection theory was also tested on pfcsp using Fuand Li's D, Fuand Li's F statistics, and Tajima's D test using DnaSP. RESULTS: In comparison with the different pfcsp reference strains, the Sudanese isolates showed high similarity with other African isolates. The results of the N-terminal region showed the presence of 2 different haplotypes with a Hapd of 0.425 ± 0.00727. The presence of the unique insertion of NNNGDNGREGKDEDKRDGNN was reported. The KLKQP motif was conserved in all the studied isolates. At the central repeat region, 11 haplotypes were seen with a Hapd of 0.779 ± 0.00097. The analysis of the genetic diversity in the C-terminal region showed the presence of 10 haplotypes with a Hapd of 0.457 ± 0.073. Several non-synonymous amino acids changes were also seen at the Th2R and the Th3R T-cell epitope regions including T317K, E317K, Q318E, K321N, I322K, T322K, R322K, K324Q, I327L, G352N, S354P, R355K, N356D, Q357E, and E361A. CONCLUSIONS: In this study, the results indicated a high conservation at the pfcsp gene. This may further contribute in understanding the genetic polymorphisms of P. falciparum prior to the deployment of the RTS,S vaccine in Sudan.


Assuntos
Variação Genética , Vacinas Antimaláricas/genética , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Estudos Transversais , Feminino , Amplificação de Genes , Haplótipos , Humanos , Masculino , Plasmodium falciparum/química , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Sudão
3.
BMC Microbiol ; 19(1): 126, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185900

RESUMO

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is known as a leading cause of morbidity and mortality. Investigation of the MRSA's virulence and resistance mechanisms is a continuing concern toward controlling such burdens through using high throughput whole Genome Sequencing (WGS) and molecular diagnostic assays. The objective of the present study is to perform whole-genome sequencing of MRSA isolated from Sudan using Illumina Next Generation Sequencing (NGS) platform. RESULTS: The genome of MRSA strain SO-1977 consists of 2,827,644 bp with 32.8% G + C, 59 RNAs and 2629 predicted coding sequences (CDSs). The genome has 26 systems, one of which is the major class in the disease virulence and defence. A total of 83 genes were annotated to virulence disease and defence category some of these genes coding as functional proteins. Based on genome analysis, it is speculated that the SO-1977 strain has resistant genes to Teicoplanin, Fluoroquinolones, Quinolone, Cephamycins, Tetracycline, Acriflavin and Carbapenems. The results revealed that the SO-1977, strain isolated from Sudan has a wide range of antibiotic resistance compared to related strains. CONCLUSION: The study reports for the first time the whole genome sequence of Sudan MRSA isolates. The release of the genome sequence of the strain SO-1977 will avail MRSA in public databases for further investigations on the evolution of resistant mechanism and dissemination of the -resistant genes of MRSA.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/microbiologia , Sequenciamento Completo do Genoma/métodos , Antibacterianos , Composição de Bases , Farmacorresistência Bacteriana , Tamanho do Genoma , Genoma Bacteriano , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Anotação de Sequência Molecular , Sudão , Fatores de Virulência/genética
4.
Malar J ; 18(1): 333, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31570093

RESUMO

BACKGROUND: Malaria caused by Plasmodium falciparum parasite is still known to be one of the most significant public health problems in sub-Saharan Africa. Genetic diversity of the Sudanese P. falciparum based on the diversity in the circumsporozoite surface protein (PfCSP) has not been previously studied. Therefore, this study aimed to investigate the genetic diversity of the N-terminal region of the pfcsp gene. METHODS: A cross-sectional molecular study was conducted; 50 blood samples have been analysed from different regions in Sudan. Patients were recruited from the health facilities of Khartoum, New Halfa, Red Sea, White Nile, Al Qadarif, Gezira, River Nile, and Ad Damazin during malaria transmission seasons between June to October and December to February 2017-2018. Microscopic and nested PCR was performed for detection of P. falciparum. Merozoite surface protein-1 was performed to differentiate single and multiple clonal infections. The N-terminal of the pfcsp gene has been sequenced using PCR-Sanger dideoxy method and analysed to sequences polymorphism including the numbers of haplotypes (H), segregating sites (S), haplotypes diversity (Hd) and the average number of nucleotide differences between two sequences (Pi) were obtained using the software DnaSP v5.10. As well as neutrality testing, Tajima's D test, Fu and Li's D and F statistics. RESULTS: PCR amplification resulted in 1200 bp of the pfcsp gene. Only 21 PCR products were successfully sequenced while 29 were presenting multiple clonal P. falciparum parasite were not sequenced. The analysis of the N-terminal region of the PfCSP amino acids sequence compared to the reference strains showed five different haplotypes. H1 consisted of 3D7, NF54, HB3 and 13 isolates of the Sudanese pfcsp. H2 comprised of 7G8, Dd2, MAD20, RO33, Wellcome strain, and 5 isolates of the Sudanese pfcsp. H3, H4, and H5 were found in 3 distinct isolates. Hd was 0.594 ± 0.065, and S was 12. The most common polymorphic site was A98G; other sites were D82Y, N83H, N83M, K85L, L86F, R87L, R87F, and A98S. Fu and Li's D* test value was - 2.70818, Fu and Li's F* test value was - 2.83907, indicating a role of negative balancing selection in the pfcsp N-terminal region. Analysis with the global pfcsp N-terminal regions showed the presence of 13 haplotypes. Haplotypes frequencies were 79.4%, 17.0%, 1.6% and 1.0% for H1, H2, H3 and H4, respectively. Remaining haplotypes frequency was 0.1% for each. Hd was 0.340 ± 0.017 with a Pi of 0.00485, S was 18 sites, and Pi was 0.00030. Amino acid polymorphisms identified in the N-terminal region of global pfcsp were present at eight positions (D82Y, N83H/M, K85L/T/N, L86F, R87L/F, A98G/V/S, D99G, and G100D). CONCLUSIONS: Sudanese pfcsp N-terminal region was well-conserved with only a few polymorphic sites. Geographical distribution of genetic diversity showed high similarity to the African isolates, and this will help and contribute in the deployment of RTS,S, a PfCSP-based vaccine, in Sudan.


Assuntos
Genética Populacional , Plasmodium falciparum/genética , Polimorfismo Genético , Proteínas de Protozoários/genética , Estudos Transversais , Haplótipos , Humanos , Malária Falciparum/sangue , Malária Falciparum/parasitologia , Análise de Sequência de DNA , Sudão
5.
J Contemp Dent Pract ; 19(5): 527-534, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29807962

RESUMO

OBJECTIVE: The aim of this study is to evaluate the effect of the subgingival application of 0.8% hyaluronic acid (HA) gel (GENGIGEL®) as an adjunct to scaling and root planing (SRP) on clinical parameters and expression of human beta defensin-2 (hBD-2) in patients with moderate to severe chronic periodontitis. MATERIALS AND METHODS: In this randomized, split mouth design study, 24 participants with moderate to severe chronic periodontitis were evaluated after full mouth SRP. In the test sites 1 mL of 0.8% hyaluronan gel was applied subgingivally after SRP at baseline and 1 week post therapy. Plaque index (PI), gingival index (GI), papillary bleeding index (PBI), periodontal probing depth (PPD), and clinical attachment loss (CAL) were recorded and gingival crevicular fluid (GCF) samples were collected at baseline, after 6 and 12 weeks. Expression of human beta defensin-2 (hBD-2) was analyzed by enzyme-linked immunosorbent assay. RESULTS: At baseline, there were no statistical differences between test and control sites in all clinical parameters and hBD-2 expression. An improvement of PI, GI, PBI, PPD, and CAL was observed at 6 and 12 weeks (p < 0.05) in both groups. Clinically, it was noticed that all indices except CAL had more statistically significant reduction in test sites than control sites at 6 and 12 weeks. The hBD-2 levels were significantly higher in the test sites than in the control sites at 6 and 12 weeks. CONCLUSION: The local application of 0.8% hyaluronan gel with SRP have a positive effect on periodontal health of moderate to severe chronic periodontitis patients after 6 and 12 weeks. CLINICAL SIGNIFICANCE: Subgingival application of 0.8% HA gel following SRP has shown anti-inflammatory effect and has a beneficial effect on clinical parameters in moderate to severe chronic periodontitis patients.


Assuntos
Periodontite Crônica/terapia , Ácido Hialurônico/administração & dosagem , Administração Tópica , Adulto , Biomarcadores/metabolismo , Periodontite Crônica/diagnóstico , Periodontite Crônica/genética , Terapia Combinada , Raspagem Dentária , Relação Dose-Resposta a Droga , Feminino , Géis , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Aplainamento Radicular , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem , beta-Defensinas/genética , beta-Defensinas/metabolismo
6.
BMC Womens Health ; 17(1): 90, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-28950833

RESUMO

BACKGROUND: Implantation defect is one of these contributing factors for unexplained infertility. In the mid-luteal phase, when implantation is expected to happen, Integrins expression is remarkably increased. So, Integrins could potentially serve as markers for the frame of the window of implantation. αVß3 integrin could have a role as a potential receptor for embryonic attachment. The aim of the current study is to investigate whether the women with unexplained infertility have a pattern of expression of endometrial αvß3 integrin that could differ from those who have normal fertility or not. METHOD: Two groups of women have been included in this study. The first group was the Unexplained Infertility Group. This group included women diagnosed with unexplained primary infertility. The second group was the fertile Group, which included fertile parous women presented to the family planning clinic seeking contraception. 2D transvaginal ultrasound scan (TVS) was performed six days after detecting urinary LH surge. (TVS) was used to measure endometrial thickness, and subendometrial blood flow color Doppler Resistance Index (RI). On the same day of transvaginal ultrasound, endometrial samples were taken using the Endocell® office suction sampler for Immunohistochemistry (IHC) study using monoclonal mouse IgG antibodies to detect endometrial αvß3 integrin. RESULTS: Thirty-five fertile women with a diagnosis of unexplained infertility were included as a group I [Unexplained infertility Group] along with an equal number of fertile women as group II [Fertile Group]. The group of women with a diagnosis of unexplained infertility had a significantly lower αvß3 integrin score when compared to the fertile group (median score 0, range:0-2 and median score 1, range: 1-3 and for infertile and fertile groups respectively, P < 0.0001). In addition, the unexplained infertility group had significantly higher subendometrial flow RI and Significantly thinner endometrial thickness. CONCLUSION: This study showed that Alpha v Beta 3 integrin is a significantly lower in endometrium in cases of unexplained infertility, which may suggest that underexpression of Alpha v Beta 3 integrin in human endometrium could be linked to defective uterine receptivity, and play a role as an unrecognized cause of infertility in this population of women. We need larger studies of adequate statistical power, ideally investigating more than one menstrual cycle in the same woman, to investigate the usefulness of using these molecular molecules in clinical practice.


Assuntos
Endométrio/metabolismo , Fertilidade/genética , Infertilidade Feminina/genética , Infertilidade Feminina/metabolismo , Integrina alfaVbeta3/genética , Integrina alfaVbeta3/metabolismo , Útero/metabolismo , Adulto , Endométrio/diagnóstico por imagem , Feminino , Fertilidade/fisiologia , Humanos , Imuno-Histoquímica , Estudos Prospectivos , Ultrassonografia , Ultrassonografia Doppler em Cores , Útero/diagnóstico por imagem , Adulto Jovem
7.
Ir J Med Sci ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602618

RESUMO

INTRODUCTION: Opioids are commonly added to local anaesthetic for subarachnoid block for caesarean section due to their synergistic effects. The physiochemical characteristics of opioids suggest premixing with hyperbaric bupivacaine may limit their distribution within the CSF. We studied the effect of a separate injection with a combination of bupivacaine, morphine and fentanyl on block characteristics, haemodynamic changes, postoperative pain and patient satisfaction. METHOD: Following ethical approval and informed consent, a prospective double-blinded randomised controlled trial was performed in a university hospital. A total of 126 patients undergoing caesarean section were randomised to two groups. In group M, the premixed group, patients received 12 mg of hyperbaric bupivacaine, 20 mcg of fentanyl and 100 mcg of morphine injected as a single mixture. In group S, the separate injection group, patients received the same drugs in separate injections. Measurements included haemodynamics, block distribution, intra- and postoperative pain, as well as patient satisfaction. RESULTS: Patients in both groups had similar block height, time to maximum sensory block, time to block regression and motor block. However, haemodynamics were different between the groups. The proportion of systolic hypotension episodes was greater in group S [159/1320 (12.05%)] than group M [113/1452 (7.78%)], with P = 0.0002. Moreover, a greater amount of ephedrine was administered in group S than group M, with values 12.09 (8.1) and 9.09 (8.5) mg respectively (P = 0.001). Additionally, postoperative pain, as measured by the Visual Analogue Scale (VAS), was greater in group M, with a VAS of 4.6 (1.7), vs. group S, which recorded a VAS of 3.8 (2.0) (P = 0.017). CONCLUSION: Sequential injection of intrathecal opioids and hyperbaric bupivacaine resulted in greater early haemodynamic instability and slightly better postoperative analgesia without any difference in block height or patient satisfaction. CLINICAL TRIAL REGISTRATION: NCT04403724.

8.
Pediatr Hematol Oncol ; 30(4): 328-35, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23574301

RESUMO

BACKGROUND: Chemotherapy-induced infertility is a common side effect observed in women of fertile age after treatment for malignant disease. OBJECTIVES: to study gonadal function and fertility in female survivors of childhood malignancies. PATIENTS AND METHODS: Study included 30 female cancer survivors and 30 age-matched healthy females as a control group. Data collected regarding; type of malignancy, age at diagnosis, duration on and off treatment, treatment received (radiation or chemotherapeutic regimens), sexual, menstrual, pregnancy, and fertility histories were also recorded. Laboratory investigations included; T4, thyroid stimulating hormone (TSH), leutinizing hormone (LH), follicular stimulating hormone (FSH), and anti-Mullerian hormone (AMH). Pelviabdominal ultrasound was done to estimate the mean ovarian volume. RESULTS: Among patients; 80% had normal menarche and 6 (20%) had delayed menarche (P > .05). There was higher LH and FSH levels and lower AMH levels in patients (P < .05) with no significant difference in thyroid function tests (P > .05). Lower mean ovarian volume was observed among female survivors (6.32 ± 2.31 cm(3)) (P = .041). There was a higher FSH and LH levels among female survivors of solid tumors compared to those with hematological tumors (P = .05 and .04 respectively). There was a significant positive correlation between FSH level and patients' age at start of malignancy (r = 0.65, P = .014), age of menarche (r = 0.74, P = .036), and duration of treatment (r = 0.54, P = .025).There was a significant negative correlation between age of menarche and AMH level (r = -0.61, P = .03). CONCLUSION: Female survivors of childhood malignancies had reduced ovarian reserve and reduced mean ovarian volume, especially those with older age, older age of menarche, and longer treatment duration.


Assuntos
Neoplasias/fisiopatologia , Ovário/fisiopatologia , Adolescente , Adulto , Hormônio Antimülleriano/sangue , Criança , Pré-Escolar , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Neoplasias/sangue , Neoplasias/mortalidade , Neuroblastoma/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Sobreviventes , Tumor de Wilms/fisiopatologia
9.
Nanomaterials (Basel) ; 13(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38063757

RESUMO

Three-dimensionally (3D)-printed fabricated denture bases have shown inferior strength to conventional and subtractively fabricated ones. Several factors could significantly improve the strength of 3D-printed denture base resin, including the addition of nanoparticles and post-curing factors. This study evaluated the effect of TiO2 nanoparticle (TNP) addition and the post-curing time (PCT) on the flexural properties and hardness of three-dimensionally (3D)-printed denture base resins. A total of 360 specimens were fabricated, with 180 specimens from each type of resin. For evaluating the flexural properties, bar-shaped specimens measuring 64 × 10 × 3.3 mm were used, while, for the hardness testing, disc-shaped specimens measuring 15 × 2 mm were employed. The two 3D-printed resins utilized in this study were Asiga (DentaBASE) and NextDent (Vertex Dental B.V). Each resin was modified by adding TNPs at 1% and 2% concentrations, forming two groups and an additional unmodified group. Each group was divided into three subgroups according to the PCT (15, 60, and 90 min). All the specimens were subjected to artificial aging (5000 cycles), followed by testing of the flexural strength and elastic modulus using a universal testing machine, and the hardness using the Vickers hardness test. A three-way ANOVA was used for the data analysis, and a post hoc Tukey's test was used for the pairwise comparisons (α = 0.05). Scanning electron microscopy (SEM) was used for the fracture surface analysis. The addition of the TNPs increased the flexural strength in comparison to the unmodified groups (p < 0.001), while there was no significant difference in the elastic modulus and hardness with the 1% TNP concentration. Among the TNP groups, the 2% TNP concentration significantly decreased the elastic modulus and hardness (p < 0.001). The SEM showed a homogenous distribution of the TNPs, and the more irregular fracture surface displayed ductile fractures. The PCT significantly increased the flexural strength, elastic modulus, and hardness (p < 0.001), and this increase was time-dependent. The three-way ANOVA results revealed a significant difference between the material types, TNP concentrations, and PCT interactions (p < 0.001). Both concentrations of the TNPs increased the flexural strength, while the 2% TNP concentration decreased the elastic modulus and hardness of the 3D-printed nanocomposites. The flexural strength and hardness increased as the PCT increased. The material type, TNP concentration, and PCT are important factors that affect the strength of 3D-printed nanocomposites and could improve their mechanical performance.

10.
Int J Biomater ; 2022: 6583084, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35855810

RESUMO

Purpose: Investigate the effect of low nanodiamond (ND) addition and autoclave polymerization on the flexural strength, impact strength, and hardness of polymethylmethacrylate (PMMA) denture base. Methods: A total of 240 heat polymerized PMMA were fabricated with low ND concentrations of 0.1%, 0.25%, and 0.5%, and unmodified as control. The specimens were divided equally into group I: conventionally polymerized PMMA by water bath and group II: polymerized by the autoclave. The impact strength, flexural strength, and elastic modulus were tested using the Charpy-type impact-testing machine and three-point bending test, respectively. A scanning electron microscope (SEM) was used to analyze the fractured surfaces. Surface hardness was measured by a hardness tester with a Vickers diamond. The bonding and interaction between the PMMA and ND particles were analyzed by the Fourier-transform infrared (FTIR) spectroscope. ANOVA and post hoc Tukey test were used for data analysis (α = 0.05). Results: ND addition significantly increased the flexural strength of groups I and II (p < 0.001, p=0.003); it was highest (128.8 MPa) at 0.25% ND concentration for group I and at 0.1% for group II. Elastic modulus increased at 0.1% ND for both groups (p=0.004, p=0.373), but the increase was statistically significant for group I only. Impact strength showed no significant change with the addition of ND in groups I and II (p=0.227, p=0.273), as well as surface hardness in group I (p=0.143). Hardness decreased significantly with 0.25%ND in group II. Conclusion: The addition of ND at low concentration increased the elastic modulus and flexural strength of conventionally and autoclave polymerized denture base resin. Autoclave polymerization significantly increased the flexural strength, impact strength, and hardness of unmodified PMMA and hardness of 0.5% ND group.

11.
Int J Biomater ; 2021: 6668577, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33927766

RESUMO

OBJECTIVES: This study aimed to evaluate denture cleanser effects on color stability, surface roughness, and hardness of PMMA denture base resin reinforced with nano-ZrO2. MATERIALS AND METHODS: A total of 420 specimens were fabricated of unreinforced and nano-ZrO2 reinforced acrylic resin at 2.5% and 5%, resulting in 3 main groups. These groups were further subdivided (n = 10) according to immersion solution (distilled water, Corega, sodium hypochlorite, and Renew) and immersion duration. Surface roughness, hardness, and color were measured at baseline (2 days-T 0) in distilled water and then after 180 and 365 days of immersion (T 1 & T 2) in water or denture cleansing solutions. Data was collected and analyzed using two-way ANOVA followed by Bonferroni post hoc test (α = 0.05). RESULTS: Surface roughness increased significantly after denture cleanser immersion of unmodified and nano-ZrO2-modified PMMA materials while hardness decreased (P < 0.001). The denture cleansers significantly affected the color of both PMMA denture bases (P < 0.001). The immersion time in denture cleansers significantly affected all tested properties (P < 0.001). Within denture cleansers, NaOCl showed the highest adverse effects (P < 0.05) while Renew showed the least adverse effects. CONCLUSION: Denture cleansers can significantly result in color change and alter the surface roughness and hardness of denture base resin even with ZrO2 nanoparticles addition. Therefore, they should be carefully used.

12.
J Immunother Cancer ; 8(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32737143

RESUMO

BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC. METHODS: A retrospective case series describing the use of LEN/PEM as salvage therapy in patients with progressive/metastatic ACC. RESULTS: Eight patients were treated with the LEN/PEM combination therapy. Half were female, and the median age at time of diagnosis was 38 years (range 21-49). Three (37.5%) patients had hormonally active ACC. The median number of prior lines of systemic therapy was 4 (range 2-9). Six (75%) patients had had disease progression on prior CPIs and five (62.5%) patients had progressed on prior MKI therapy. The median progression-free survival was 5.5 months (95% CI 1.8-not reached) and median duration of therapy was 8.5 months (range 2-22). Two (25%) patients had a partial response, one (12.5%) patient had stable disease, and five (62.5%) patients had progressive disease. None of the eight patients stopped therapy because of adverse events. CONCLUSIONS: In our small cohort of heavily pretreated patients with ACC, the combination of LEN/PEM was associated with objective responses in a subset of patients without significant toxicity. This combination should be formally investigated in phase II clinical trial with robust correlative studies to identify predictors for response.


Assuntos
Carcinoma Adrenocortical/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Terapia de Salvação/métodos , Adulto , Anticorpos Monoclonais Humanizados/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/farmacologia , Quinolinas/farmacologia , Estudos Retrospectivos , Adulto Jovem
13.
BMC Res Notes ; 13(1): 512, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33160417

RESUMO

OBJECTIVES: Malaria infection is still known to be a worldwide public health problem, especially in tropical and sub-tropical African countries like Sudan. A pilot study conducted to describe the trend of P. falciparum drug resistance markers in 2017-2018 in comparison to CQ and AS/SP eras in Sudan. The Pfcrt, Pfmdr-1, Pfdhfr, and Pfdhps genes were investigated. Data deposited by the worldwide antimalarial resistance network was consulted, and the molecular markers previously reported from Sudan were analyzed. RESULTS: Drug molecular markers analysis was successfully done on 20 P. falciparum isolates. The Pfcrt K76 showed high frequency; 16 (80%). For the Pfmdr-1, 9 (45%) isolates were carrying the N86 allele, and 11 (55%) were 86Y allele. While the Y184F of the Pfmdr-1 showed a higher frequency of 184F compared to Y184; 16 (80%) and 4 (20%), respectively. In the Pfdhfr, 51I allele showed higher frequency compared to N51; 18 (90%) and 2 (10%), respectively. For S108N, 18 (90%) were 108 N and 2 (10%) were S108. In the Pfdhps, all isolates were carrying the mutant alleles; 437G and 540E. The frequency distribution of the Pfcrt, Pfmdr-1, Pfdhfr, Pfdhps was significantly different across the whole years in Sudan.


Assuntos
Antimaláricos , Malária Falciparum , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Combinação de Medicamentos , Resistência a Medicamentos/genética , Humanos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Projetos Piloto , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Pirimetamina/uso terapêutico , Sudão , Sulfadoxina/uso terapêutico
14.
BMC Res Notes ; 13(1): 317, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32616024

RESUMO

OBJECTIVES: IL-17A G197A and IL-17F A7488G polymorphisms has been identified to be associated with the susceptibility to many diseases. This study aimed to investigate the frequency distribution of IL-17A G197A and IL-17F A7488G polymorphisms among healthy Sudanese population. A descriptive cross-sectional hospital-based molecular study conducted in different sites throughout Sudan. Two ml blood samples were collected from 717 healthy participants. Demographic data and the medical history of the participants were collected. RESULTS: Of the 717 participants, 355 (49.5%) were males and 362 (50.5%) were females, their mean age was 30.2 ± 17.2 and 32.2 ± 16.5, respectively. For IL-17A, the most frequent genotype detected among males and females was IL-17A heterozygote allele (AG); 215 (60.6%) and 194 (53.6%), respectively. Whereas, for IL-17F, the most frequent allele among males and females was the homozygote allele (AA); 298 (83.9%) for males and 322 (89.0%) for females. HWE for genotype distributions of IL-17A was showing statistical insignificance for IL-17A among males and females, P value 0.614. While HWE for IL-17F reached the equilibrium level, P value 0.048. The most frequent age group was those aged between 21 to 40 years; 281 (39.2%). Arab constituted the major ethnicity of the study participants; 418 (58.3%), P value 0.034.


Assuntos
Interleucina-17/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Frequência do Gene , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA , Sudão , Adulto Jovem
15.
Saudi Med J ; 29(9): 1289-93, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18813414

RESUMO

OBJECTIVE: To evaluate disturbances in the coagulation system in female patients with thyroid disorders in order to assess the effects of thyroid diseases on coagulation parameters. METHODS: This study was conducted in Khartoum state, the national capital of Sudan from February 2007 and February 2008 The study included 30 patients with clinical hypothyroidism, and 30 patients with sub- clinical hypothyroidism (21 of them were recruited before starting the treatment). Also, the study included 30 patients with clinical hyperthyroidism, 30 with sub-clinical hyperthyroidism, (37 of them were recruited before starting the treatment) and 30 normal individuals as the control group. Prothrombin time (PT), activated partial thromboplastin time, fibrinogen level, and platelets count were performed in patients and control samples. RESULTS: A significantly decrease in PT was observed in hypothyroid patients, and hyperthyroid patients compared to the control group. Activated thromboplastin time was significantly decreased only in hyperthyroid patients, compared to the control group. Moreover, fibrinogen level was significantly increased in hyperthyroid patients compared to hypothyroid patients. CONCLUSION: The study concluded that minor coagulation abnormalities were observed in both subclinical hypo- and hyperthyroidism compared to clinical hypo- and hyperthyroidism. Platelets count was also slightly decreased in both types of the disease. There was no significant effect of the treatment and age of such patients on the measured parameters. The study recommended to screen female patients with hypo- and hyperthyroidism for coagulation defect, to avoid the risk of such complications.


Assuntos
Coagulação Sanguínea , Hipertireoidismo/sangue , Hipotireoidismo/sangue , Feminino , Humanos , Sudão
16.
Genome Announc ; 5(42)2017 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-29051236

RESUMO

Methicillin-resistant Staphylococcus aureus is increasingly becoming resistant to most antibiotics and consequently has become a challenging public health problem in Sudan. The present study documented the first complete genome sequence of strain SO-1977, isolated from a contaminated wound in Sudan.

17.
Saudi Med J ; 27(7): 986-91, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16830016

RESUMO

OBJECTIVE: To eliminate malaria parasites in donors' blood in vitro for eradication of transfusion-induced malaria. METHODS: We conducted the study at Ahmed Gasim Hospital in Khartoum, Sudan, between January 2005 and January 2006. Out of 4484 blood samples screened for malaria parasite microscopically, only 30 (200 ml each) satisfied the inclusion criteria of this study. The samples were subdivided equally into 4 portions. Three concentrations of quinine were separately added to 3 specimens while the fourth left without quinine (control). Blood specimens were tested on the day of collection by hematological and biochemical techniques simultaneously, and after 24 and 48 hours at 4-6 degrees celcius by the same techniques. RESULTS: The number of malaria parasites killed were found to be proportional to the concentrations of quinine and to the storage period, while donors' blood samples without quinine revealed a stable number of the viable parasites during the storage. Quinine was highly effective within 24 hours storage. The detected lethal dose of the applied drug to malaria parasites was generally safe to all constituents of the stored blood. CONCLUSION: Our study shows that quinine could be used for the eradication of transfusion-induced malaria by in vitro processing of donors blood. The optimal doses could be added to bags' blood post phlebotomy.


Assuntos
Antimaláricos/farmacologia , Armazenamento de Sangue/métodos , Sangue/efeitos dos fármacos , Malária Falciparum/prevenção & controle , Plasmodium falciparum/efeitos dos fármacos , Quinina/farmacologia , Animais , Sangue/parasitologia , Contagem de Colônia Microbiana , Humanos , Técnicas In Vitro , Malária Falciparum/transmissão , Testes de Sensibilidade Parasitária , Plasmodium falciparum/crescimento & desenvolvimento , Sudão , Fatores de Tempo
18.
Saudi J Biol Sci ; 23(6): 713-717, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27872566

RESUMO

The current study was carried out to evaluate the phenotypic and genotypic characterization of avian pathogenic Escherichia coli recovered from Riyadh, Saudi Arabia. During the period of 10th February-30th May 2015, 70 E. coli strains were isolated from chicken farms located in Riyadh, Saudi Arabia. All strains were tested phenotypically by standard microbiological techniques, serotyped and the virulence genes of such strains were detected by polymerase chain reaction (PCR). Most of the recovered strains from chickens belonged to serotype O111:K58 25 strains (35.7%), followed by serotype O157:H7 13 strains (18.57%), followed by serotype O114:K90 10 strains (14.29%), then serotype O126:K71 9 strains (12.9%), serotype O78:K80 8 strains (11.43%) and in lower percentage serotype O114:K90 and O119:K69 5 strains (7.14%). The virulence genotyping of E. coli isolates recovered from broilers revealed the presence of the uidA gene in all the field isolates (6 serovars) examined in an incidence of 100%, as well as the cvaC gene was also present in all field isolates (6 serovars), while the iutA gene and the iss gene were detected in 5 out of 6 field serovars in an incidence of 81.43% and 64.29%, respectively. Phenotypical examination of the other virulence factors revealed that 65 isolates were hemolytic (92.9%), as well as 15 isolates (21.42%) were positive for enterotoxin production. Meanwhile, 21 isolates (30%) were positive for verotoxin production, 58 isolates (82.86%) for the invasiveness and 31 isolates (44.29%) for Congo red binding activities of the examined serotypes.

19.
Saudi J Biol Sci ; 23(6): 718-723, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27872567

RESUMO

Corynebacterium pseudotuberculosis (C. pseudotuberculosis) is a causative organism of caseous lymphadenitis (CLA) in sheep and acute disease in buffaloes known as oedematous skin disease (OSD). Human affected with the disease show liver abscess and abscess in the internal lymph nodes. The vaccination against CLA up till now occurs by using formalin inactivated whole cells of biovar 1 (sheep strain). Combined vaccine composed of formalin inactivated whole cells of sheep strain and recombinant phospholipase D (rPLD) and another vaccine composed of formalin inactivated whole cells (buffalo origin) and rPLD were prepared in Biotechnology center for services and Researches laboratory at Cairo university and applied for protection against CLA. Both vaccines induced complete protection (100%) against challenge with virulent biovar 1 or biovar 2. Also vaccination against OSD was performed by two types of vaccines. Vaccine-1 was composed of formalin inactivated whole cell biovar 1 combined with rPLD and the second vaccine was composed of formalin inactivated whole cells of biovar 2 combined with rPLD. No lesions developed in vaccinated and non vaccinated buffaloes challenged with C. pseudotuberculosis biovar revealing that biovar 1 C. pseudotuberculosis is not infective for buffaloes. Buffaloes vaccinated with the second vaccine and control non vaccinated animals challenged with biovar 2 (buffalo origin) resulted in development of OSD in all animals. This indicates that OSD results due to production of toxin (s) other than PLD. Discovering this toxin (s) is of value in formulation of a future vaccine against OSD.

20.
Am J Trop Med Hyg ; 73(6): 1119-23, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16354823

RESUMO

Transfusion-induced malaria is a problem because of the large number of parasites infused and the weakness of transfused patients. Screening of blood donors or treatment of transfused patients or prospective donors does not eliminate this hazard. It is essential to kill the parasite in vitro in the blood of donors before transfusion. A total of 4,484 blood donors were screened for malaria parasite microscopically using the Giemsa staining technique. Only 30 matched the inclusion criteria of this study. Blood samples were divided into four equal samples. Three concentrations of sulfadoxine-pyremthamine (SP) were added to 90 specimens, and none was added to 30 specimens (controls). Blood specimens were then tested by parasitic, biochemical, and hematologic techniques on the day of collection and after 24 and 48 hours of storage in a blood bank refrigerator. The reduction of malaria parasites was proportional to the concentrations of SP and to the storage period. Blood samples without SP had steady number of the parasites. The lethal dose of SP (the dose that killed 99% of the malaria parasites within 24 hours) was 179.65 mug/L and was highly effective within the 24-hour storage period. This dose did not affect constituents of the stored blood. Thus, for eradication of transfusion-induced malaria by in vitro processing of donors blood, SP is a safe and effective drug. It is recommended that optimal doses of SP be added to donated blood prior to phlebotomy.


Assuntos
Antimaláricos/administração & dosagem , Antimaláricos/farmacologia , Doadores de Sangue , Malária Falciparum/prevenção & controle , Plasmodium falciparum/efeitos dos fármacos , Pirimetamina/farmacologia , Sulfadoxina/farmacologia , Adulto , Animais , Testes de Coagulação Sanguínea , Transfusão de Sangue/métodos , Patógenos Transmitidos pelo Sangue , Combinação de Medicamentos , Hematócrito , Humanos , Técnicas In Vitro , Malária Falciparum/sangue , Malária Falciparum/epidemiologia , Malária Falciparum/transmissão , Masculino , Testes de Sensibilidade Parasitária , Pirimetamina/administração & dosagem , Sudão/epidemiologia , Sulfadoxina/administração & dosagem
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