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BACKGROUND: Recurrent miscarriage (RM) is defined as the occurrence of at least two or three subsequent miscarriages within the 20th -24th weeks of pregnancy. The primary objective of this study was to investigate whether histidine-rich glycoprotein C633T single nucleotide polymorphism (HRG C633T SNP) statistically correlates with the occurrence of RM among Iranian women. METHODS AND RESULTS: Blood samples from 200 women were taken at the outset of the study. Then, the blood samples of 100 women who had a record of RM (case group) were compared with the other 100 women's blood samples who had no record of RM (control group). Following DNA extraction, the polymorphism of histidine-rich glycoprotein C633T (HRG C633T) for every case was specified and all women were genotyped by the amplification-refractory mutation system (ARMS) method. The results of the study revealed that there was a statistically significant difference between T/T genotype (OR = 3.5, CI (1.39-8.77), p = 0.007), and C/T genotype (OR = 1.83, CI (0.99-3.37), p = 0.05) in the case and control groups. Also, a statistically significant association was observed in T allelic frequency in the RM participants compared to the control group (OR = 2.01, CI (1.31-3.09), p = 0.01). CONCLUSIONS: The present study determined that there was a statistically significant relationship between HRG C633T SNP and increased RM regarding allelic and genotypical aspects. Moreover, it became apparent that women with homozygous T/T genotype were more susceptible to the risk of RM.
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Aborto Habitual , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Proteínas , Adulto , Femenino , Humanos , Embarazo , Aborto Habitual/genética , Alelos , Estudios de Casos y Controles , Frecuencia de los Genes/genética , Estudios de Asociación Genética , Genotipo , Irán , Polimorfismo de Nucleótido Simple/genética , Proteínas/genéticaRESUMEN
Leukodystrophies (LDs) are a heterogeneous group of progressive neurological disorders and characterized by primary involvement of white matter of the central nervous system (CNS). This is the first report of the Iranian LD Registry database to describe the clinical, radiological, and genomic data of Persian patients with leukodystrophies. From 2016 to 2019, patients suspicious of LDs were examined followed by a brain magnetic resonance imaging (MRI). A single gene testing or whole-exome sequencing (WES) was used depending on the neuroradiologic phenotypes. In a few cases, the diagnosis was made by metabolic studies. Based on the MRI pattern, diagnosed patients were divided into cohorts A (hypomyelinating LDs) versus cohort B (Other LDs). The most recent LD classification was utilized for classification of diagnosed patients. For novel variants, in silico analyses were performed to verify their pathogenicity. Out of 680 registered patients, 342 completed the diagnostic evaluations. In total, 245 patients met a diagnosis which in turn 24.5% were categorized in cohort A and the remaining in cohort B. Genetic tests revealed causal variants in 228 patients consisting of 213 variants in 110 genes with 78 novel variants. WES and single gene testing identified a causal variant in 65.5% and 34.5% cases, respectively. The total diagnostic rate of WES was 60.7%. Lysosomal disorders (27.3%; GM2-gangliosidosis-9.8%, MLD-6.1%, KD-4.5%), amino and organic acid disorders (17.15%; Canavan disease-4.5%, L-2-HGA-3.6%), mitochondrial leukodystrophies (12.6%), ion and water homeostasis disorders (7.3%; MLC-4.5%), peroxisomal disorders (6.5%; X-ALD-3.6%), and myelin protein disorders (3.6%; PMLD-3.6%) were the most commonly diagnosed disorders. Thirty-seven percent of cases had a pathogenic variant in nine genes (ARSA, HEXA, ASPA, MLC1, GALC, GJC2, ABCD1, L2HGDH, GCDH). This study highlights the most common types as well as the genetic heterogeneity of LDs in Iranian children.
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Enfermedades Desmielinizantes , Enfermedades Neurodegenerativas , Humanos , Niño , Irán , Heterogeneidad Genética , Imagen por Resonancia Magnética , Encéfalo , Oxidorreductasas de AlcoholRESUMEN
OBJECTIVE: The aim of the study was to investigate the safety and efficacy of pregabalin versus placebo in post-traumatic peripheral neuropathic pain (PTNP). METHODS: PubMed, Cochrane Library, Web of Science, and Google Scholar were searched for relevant evidence up to January 2022. The Cochran tool was used to assess the quality of randomized clinical trials (RCTs). Data analysis was performed using Comprehensive Meta-Analysis software. RESULTS: Three RCTs involving 821 patients were included in the meta-analysis. A significant difference was observed between pregabalin and placebo in terms of the pain score (the standardized mean difference [SMD] = -0.14, 95% CI: 0.28 to -0.006, p = 0.04) and sleep interference (MD = -0.25, 95% CI: -0.39 to -0.11, p = 0.00). There was also a significant difference between pregabalin and placebo regarding somnolence (risk ratio [RR] = 2.78; 95% CI: 1.64-4.71, p = 0.00), dizziness (RR = 4.13; 95% CI: 2.71-6.28, p = 0.00), and disturbance in attention (RR: 2.97; 95% CI: 1.02-8.65, p = 0.04). However, no significant difference was observed between pregabalin and placebo in terms of headache (RR = 1.20; 95% CI: 0.70-2.06, p = 0.50), fatigue (RR = 1.42; 95% CI: 0.82-2.47, p = 0.20), nausea (RR = 1.52; 95% CI: 0.88-2.62, p = 0.13), constipation (RR = 1.84; 95% CI: 0.78-4.29, p = 0.15), and discontinuation (RR = 1.52; 95% CI: 0.45-5.06, p = 0.49). CONCLUSION: Compared with placebo, pregabalin showed better efficacy in reducing PTNP and improving sleep interference. However, it was associated with higher adverse events. Further RCTs are needed to confirm these findings.
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Analgésicos , Neuralgia , Humanos , Pregabalina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Neuralgia/tratamiento farmacológico , Neuralgia/etiología , SueñoRESUMEN
Introduction: In late February 2020, after we had informed about the presence of some cases of COVID-19 in Iran and its rapid spread throughout the country, we decided to make the necessary arrangements for patients with critical conditions in Pediatric Intensive Care Unit (PICU) at Children's Medical Center. There are a little data on critically ill children with COVID-19 infection with ICU requirements. The aim of this study was to describe clinical characteristics, laboratory parameters, treatment, and outcomes of the pediatrics population infected by SARS-CoV-2 admitted to PICU. Materials and Methods: This study was performed between February 2020 and May 2020 in the COVID PICU of the Children's Medical Center Hospital in Tehran, Iran. Patients were evaluated in terms of demographic categories, primary symptoms and signs at presentation, underlying disease, SARS-CoV-2 RT-PCR test result, laboratory findings at PICU admission, chest X-ray (CXR) and lung CT findings, and treatment. Moreover, the need to noninvasive ventilation (NIV) or mechanical ventilation, the length of hospital stay in the PICU, and outcomes were assessed. Results: In total, 99 patients were admitted to COVID PICU, 42.4% (42 patients) were males, and 66 patients had positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction (RT-PCR). There was no statistically significant difference in the frequency of clinical signs and symptoms (except for fever) among patients with positive SARS-CoV-2 RT-PCR and negative ones. Among all admitted patients, the presence of underlying diseases was noticed in 81 (82%) patients. Of 99 patients, 34 patients were treated with NIV during their admission. Furthermore, 35 patients were intubated and treated with mechanical ventilation. Unfortunately, 11 out of 35 mechanically ventilated patients (31%) passed away. Conclusion: No laboratory and radiological findings in children infected with COVID-19 were diagnostic in cases with COVID-19 admitted to PICU. There are higher risks of severe COVID-19, PICU admission, and mortality in children with comorbidities.
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COVID-19 , Niño , Masculino , Humanos , Femenino , COVID-19/epidemiología , Pandemias , SARS-CoV-2 , Irán/epidemiología , Unidades de Cuidado Intensivo Pediátrico , Hospitales , Derivación y Consulta , Estudios Retrospectivos , Unidades de Cuidados IntensivosRESUMEN
Malaria is a deadly disease in humans caused by the Plasmodium parasite. High prevalence of malaria and resistance of malaria parasite to currently proposed drugs have increased the need to introduce and use new and effective antimalarial agents. In this study, eosin B was used as an effective antimalarial agent, the efficacy of which has already been confirmed by in vitro models. Also, for efficacy and safety improvement of eosin B, liposomal nanocarrier was used because of diversity and adaptability in controlled drug delivery and targeting. Eosin B was trapped inside liposomal nanocarriers by thin layer hydration method and its optimization was performed based on size, polydispersity index, and drug entrapment efficiency. Finally, the eosin B-loaded liposomes were tested on Plasmodium falciparum in culture to evaluate its anti-plasmodial effect. According to the results, the formulation with DSPC:cholesterol 8:1 (molar ratio) and drug concentration of 3 mg/ml was selected as the optimal form. The optimal nano-liposomes showed a size of 163.3 nm, a polydispersity index of 0.250, and an encapsulation efficiency of 69.94%. The process of drug release from nanocarriers was also obtained about 63% at the end of 72 h. Stability studies over 2 months at 25 °C and 4 °C on the optimum sample showed that the samples stored in the refrigerator were more stable in terms of size characteristics, polydispersity index, and drug entrapment efficiency. The results indicate a greater effect of liposomal-formulated eosin B on inhibiting parasite growth compared to the free eosin B.
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Antimaláricos , Malaria , Antimaláricos/uso terapéutico , Eosina I Azulada , Humanos , Liposomas , Malaria/tratamiento farmacológico , Plasmodium falciparumRESUMEN
There has been a lack of studies on bullying in non-western low-income and middle-income countries. This study reported the prevalence of traditional victimization, cybervictimization, and the combination of these, in 13 European and Asian countries, and explored how psychiatric symptoms were associated with victimization. The data for this cross-sectional, school-based study of 21,688 adolescents aged 13-15 were collected from 2011 to 2017. The main outcomes were traditional and cybervictimization obtained from student self-reports. The Strengths and Difficulties Questionnaire was used to assess psychiatric symptoms. Generalized estimating equation and logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). The mean prevalence of any victimization was 28.9%, of traditional victimization only, this was 17.7%, and for cybervictimization only this was 5.1%. Cybervictimization occurred both independently, and in combination with, traditional victimization. The mean prevalence of combined victimization was 6.1%. The mean proportion of those who were cyberbullied only among those who were either cyberbullied only or bullied both traditionally and in cyber was 45.1%. The rates of prevalence varied widely between countries. In the total sample, those who experienced combined victimization, reported the highest internalizing symptoms (girls, OR 1.25, 95% CI 1.22-1.29; boys, OR 1.29, 95% CI 1.25-1.33). The study findings suggest that anti-bullying interventions should include mental health components and target both traditional and cyberbullying. Due to the overlap between these, targeting bullying should primarily focus on how to reduce bullying behavior rather than just focusing on where bullying takes place.
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Acoso Escolar , Víctimas de Crimen , Ciberacoso , Adolescente , Acoso Escolar/psicología , Víctimas de Crimen/psicología , Estudios Transversales , Ciberacoso/psicología , Femenino , Humanos , Masculino , Instituciones AcadémicasRESUMEN
BACKGROUND: The new coronavirus outbreak quickly filled hospital beds and stunned the world. Intensive care is required for 5% of patients, and the mortality rate for critically ill patients is 49%. The "cytokine storm" is considered as the main cause of pathogenesis for coronavirus disease-19 (COVID-19)-related respiratory failure, hemoperfusion may be a modality for treatment of disease. MATERIALS AND METHODS: Thirty-seven an patients with positive real-time polymerase chain reaction for SARStions2 in an upper respiratory tract sample or typical chest computed tomography lesion were eligible for this case-control study. Patients meeting the criteria for hemoperfusion including clinical and laboratory indices, were evaluated for outcomes such as hospitalization length and mortality. Patients were divided into three groups, i.e., patients who received hemoperfusion without a need for mechanical ventilation (MV), patients who received hemoperfusion before MV, and patients who received hemoperfusion after MV. RESULTS: Among 37 patients with COVID-19 respiratory failure, 32% were female with a mean age of 55.54 (standard deviation 14.1) years. There was no statistically significant difference between the three groups in terms of length of hospital stay and intensive care unit (ICU) stay (P-tayns: 0.593 and 0.243, respectively, confidence interval [CI]: 95%). Heart rate, respiratory rate, PaO2/FIO2, high-sensitivity C-reactive protein, and ferritin significantly improved after the application of hemoperfusion in all groups (P < 0.05, CI: 95%). CONCLUSION: It seems that applying hemoperfusion in the inflammatory phase of the disease, especially before the intubation, reduce the need for MV. However, hemoperfusion does not have any impacts on the duration of hospital and ICU stay.
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Due to side-effects and inefficiency of the drugs used in malaria treatment, finding alternative medicine with less side-effects has attracted much attention. In this regard, in the present study, nanocomposite synthesized and its effects on the metabolites of P. falciparum were investigated. Subsequent to synthesis of nanocomposites, characterization was carried out using nuclear magnetic resonance (NMR), liquid chromatography-mass spectrometry (LC-MS), scanning electron microscopy, dynamic light scattering and Fourier-transform infrared tests. Solubility and drug release were measured and its toxicity on Vero cell was assessed using the MTT assay. The antiparasitic effect of the nanocomposite on the metabolites of P. falciparum was investigated by 1H NMR spectroscopy. Among synthesized nanocomposites, the average size of 239 nm showed suitable solubility in water as well as slow drug release. The MTT assay showed no toxicity for Vero cell lines. Concentrations of 2.5 µg mL-1 of nanocomposite eliminated 82.6% of the total parasites. The most effected metabolic cycles were glyoxylate and dicarboxylate metabolism. In this study, 1H NMR spectroscopy was used with untargeted metabolomics to study the effect of the nanocomposite on P. falciparum. Playing an essential role in understanding drug-target interactions and characterization of mechanism of action or resistance exhibited by novel antiprotozoal drugs, can be achieved by targeting metabolic using LC-MS.
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Antimaláricos/farmacología , Cloroquina/farmacología , Curcumina/farmacología , Dendrímeros/farmacología , Metaboloma , Nanocompuestos/análisis , Plasmodium falciparum/efectos de los fármacos , Animales , Chlorocebus aethiops , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Metabolómica , Células VeroRESUMEN
OBJECTIVE: This exploratory study examines a rural critical access hospital (CAH) staff's perception of current obstacles and needs concerning the physical environment. BACKGROUND: CAH intends to improve access to healthcare, coordinate with experts and providers, and serve as the rural population's healthcare hub. It is imperative to understand environmental qualities that impact the quality of care to develop effective policies and design guidelines for rural healthcare. Nevertheless, a limited number of studies have focused on user or organizational outcomes related to the physical environment of rural healthcare settings. METHODS: This cross-sectional exploratory qualitative case study was conducted as part of the facility planning process for a CAH in rural North Carolina. Hospital staff participated in a survey exploring their satisfaction with the overall physical environment privacy, space allocation, and department adjacency. An open-ended question asked staff to elaborate on needed improvements and changes in their department. RESULTS: Findings show low satisfaction levels for space allocations for emergency department, lab, surgery, and wound care. Safety and quality were the two emerging outcomes of the physical environment's shortcomings. Two clusters emerged from the content analysis, representing facility needs (rightly sized spaces, functional needs, COVID-19 needs, and improved access) and ambient conditions (clutter, visibility, flooring quality, noise, privacy, cleanliness, aesthetics, and temperature). CONCLUSION: The findings from this study suggest that the interior and exterior facility and ambient conditions of the CAH play a key role in quality and safety outcomes.
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Atención a la Salud , Personal de Hospital , Humanos , Estudios Transversales , Servicio de Urgencia en Hospital , HospitalesRESUMEN
OBJECTIVE: This study aimed to investigate the effect of spatial adjacencies on nurses' walking patterns and the subsequent impact on staff satisfaction with perceived accessibility and adjacency-related issues. BACKGROUND: Recognizing the crucial importance of spatial adjacencies in healthcare facilities is essential, as they significantly affect staff morale, fatigue management, operational efficiency, error reduction, and overall patient care excellence, highlighting the need for objective assessments to evaluate the impact of facility layout and space configuration on workflow patterns and staff satisfaction in patient care units. METHODS: Integrating on-site observations with survey data, we explored how spatial adjacencies affect staff walking behavior and satisfaction in two med-surgical unit floors. RESULTS: The findings highlighted a significant frequency of movements between nurse stations, patient rooms, and medication areas. Regression analysis identified several contributing factors to staff satisfaction, including the proximity of supplies, team visibility, ease of access across departments, and the location of equipment rooms. Specifically, satisfaction with the proximity of supplies was positively associated with increased provider satisfaction with workflow, quality of care, and workplace. Additionally, valuable feedback from staff revealed concerns regarding break room placement, medication area functionality, and disparities in the availability of supplies. CONCLUSION: This study highlighted the critical need for carefully planned spatial adjacency strategies to enhance workflow efficiency and raise clinical staff satisfaction within healthcare facilities. The actionable insights gleaned from this research offer valuable direction to architects, healthcare administrators, and design professionals, enabling the creation of environments that positively resonate with healthcare providers and improve healthcare operations.
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Purpose: Recurrent miscarriage (RM) is a significant reproductive concern affecting numerous women globally. Genetic factors are believed to play a crucial role in RM, making the histidine-rich glycoprotein (HRG) gene, a topic of interest due to its potential involvement in angiogenesis. This study is aimed at investigating the association between the HRG rs10770 genotype and RM. Method: Blood samples were collected from a total of 200 women at the beginning of the study. Subsequently, a comparative analysis was conducted between the blood samples of 100 women with a history of RM (case group) and the blood samples of another 100 healthy women (control group). HRG rs10770 genotyping was performed through polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP), followed by statistical analysis to evaluate the relationship between HRG rs10770 genotype and RM. Results: The results indicated a significant statistical difference between the C/C genotype (OR = 3.32, CI: 1.22-9.04, p = 0.01) and the C/T genotype (OR = 1.24, CI: 0.67-2.30, p = 0.47) in both the case and control groups. Additionally, a significant correlation was observed in the C allelic frequency among RM participants compared to the control group (OR = 1.65, CI: 1.06-2.58, p = 0.02). Conclusion: The study highlights the importance of HRG rs10770 in understanding RM, shedding light on its implications for reproductive health. Furthermore, it became evident that women carrying the homozygous C/C genotype exhibited increased susceptibility to the risk of RM.
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Aborto Habitual , Predisposición Genética a la Enfermedad , Adulto , Femenino , Humanos , Embarazo , Aborto Habitual/genética , Alelos , Estudios de Casos y Controles , Estudios de Asociación Genética , Genotipo , Irán , Polimorfismo de Nucleótido Simple/genética , Proteínas/genéticaRESUMEN
BACKGROUND: Hospitals should have effective and efficient organizational charts to face the changing healthcare environment. Thus, for this purpose, the present study seeks to compile an organizational chart for Iranian hospitals. MATERIALS AND METHODS: The present study was conducted in two phase overview and qualitative (using focus group discussion). In the overview phase, the organizational charts of hospitals were analyzed in terms of complexity (i.e., degree of horizontal and vertical separations), and the initial hospital organizational chart was developed based on the results. Subsequently, experts were interviewed in a focus group discussion to finalize and validate the initial organizational chart. RESULTS: The final organizational chart was designed to contain features such as internal divisions, specialization, reduction of organizational hierarchies, expansion of supervision scope, and moderate-sized organizational pyramid. CONCLUSION: Using designed organizational chart would eliminate the redundant managerial levels since it reduces organizational hierarchies to two levels of management, expands the supervision scopes, fosters a moderate-sized organizational pyramid, and catalyzes communications.
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Administración Hospitalaria , Hospitales , Irán , Atención a la Salud , Grupos FocalesRESUMEN
BACKGROUND: Malaria is still the deadliest parasitic disease caused by Plasmodium spp. Due to drug resistance and their unpleasant side effects, of conventional researchers are enormously seeking to achieve antimalarial drugs with more curative effective, less toxic and cost-affordable drugs using more advanced technology such as nanodrugs. PURPOSE: The present study aimed to examine the antimalarial effects of a novel synthesized nonochloroquine-loaded curcumin relying on dendrimer G2 in susceptible mice. METHODS: Antimalarial activity and toxicity of the nanocomposite were examined on BALB/C mice with microscopy, checking RBCs morphology and related enzymatic activity rate. RESULTS: The maximum inhibitory effect of the nanocomposite was seen at 10 mg/kg, killing 98% of P. berghei compared to sole chloroquine, whereas ED50 was reported at 5.5 mg/kg. The safety of the synthesized nanocomposite was confirmed with biochemical tests with no detrimental effects on mice. The sustainability and longevity of the nanodrug increased significantly with the NDC-CQ assay compared to the control groups. CONCLUSION: The study showed that nonochloroquine-loaded curcumin had a promising inhibitory effect on P. berghei growth in infected mice compared to standard drugs. However, further studies and clinical trials with large samples are recommended to study different aspects of using nanodrug.
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Antimaláricos , Cloroquina , Curcumina , Malaria , Ratones Endogámicos BALB C , Plasmodium berghei , Animales , Curcumina/administración & dosificación , Curcumina/farmacología , Antimaláricos/administración & dosificación , Antimaláricos/farmacología , Malaria/tratamiento farmacológico , Cloroquina/farmacología , Cloroquina/administración & dosificación , Ratones , Plasmodium berghei/efectos de los fármacos , Nanocompuestos/química , Eritrocitos/efectos de los fármacos , Eritrocitos/parasitología , Dendrímeros/químicaRESUMEN
Metabolomics plays a crucial role in identifying molecular biomarkers that can differentiate pathological conditions. In the case of thyroid cancer, it is essential to accurately diagnose malignancy from benignity to avoid unnecessary surgeries. The objective of this research was to apply untargeted NMR-based metabolomics in order to identify metabolic biomarkers that can distinguish between plasma samples of patients with papillary thyroid cancer (PTC) and multinodular goiter (MNG), as well as PTC and healthy individuals. The study included a cohort of 55 patients who were divided into three groups: PTC (n=20), MNG (n=16), and healthy (n=19). Plasma samples were collected from all participants and subjected to 1H NMR spectroscopy. Differential metabolites were identified using chemometric pattern recognition algorithms. The obtained metabolic profile had the potential to differentiate PTC from healthy plasma, but not from MNG. In patients diagnosed with PTC, a total of 18 compounds were discovered, revealing elevated levels of leucine, lysine, and 4-acetamidobutyric acid, while acetate, proline, acetoacetate, 3-hydroxybutyrate, glutamate, pyruvate, cystine, glutathione, asparagine, ethanolamine, histidine, tyrosine, myo-inositol, and glycerol along with a lipid compound were found to be lower in comparison to those of healthy individuals. According to the area under the curve (AUC) of the receiver operating characteristic curve, this particular profile exhibited an impressive capability of 85% to discern PTC from healthy subjects (AUC=0.853, sensitivity=78.95, specificity=84.21). The utilization of the 1H NMR-based metabolomics approach revealed considerable promise in the identification of PTC from healthy plasma specimens. The modifications noticed in the plasma metabolites have the potential to act as practical biomarkers that are non-invasive and could suggest transformations in the metabolic profile of thyroid tumors.
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Biomarcadores de Tumor , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/diagnóstico , Espectroscopía de Protones por Resonancia Magnética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Metabolómica/métodos , Espectroscopía de Resonancia Magnética/métodosRESUMEN
OBJECTIVE: Mitochondrial leukodystrophies (MLs) are mainly caused by impairments of the mitochondrial respiratory chains. This study reports the mutation and phenotypic spectrum of a cohort of 41 pediatric patients from 39 distinct families with MLs among 320 patients with a molecular diagnosis of leukodystrophies. METHODS: This study summarizes the clinical, imaging, and molecular data of these patients for five years. RESULTS: The three most common symptoms were neurologic regression (58.5%), pyramidal signs (58.5%), and extrapyramidal signs (43.9%). Because nuclear DNA mutations are responsible for a high percentage of pediatric MLs, whole exome sequencing was performed on all patients. In total, 39 homozygous variants were detected. Additionally, two previously reported mtDNA variants were identified with different levels of heteroplasmy in two patients. Among 41 mutant alleles, 33 (80.4%) were missense, 4 (9.8%) were frameshift (including 3 deletions and one duplication), and 4 (9.8%) were splicing mutations. Oxidative phosphorylation in 27 cases (65.8%) and mtDNA maintenance pathways in 8 patients (19.5%) were the most commonly affected mitochondrial pathways. In total, 5 novel variants in PDSS1, NDUFB9, FXBL4, SURF1, and NDUSF1 were also detected. In silico analyses showed how each novel variant may contribute to ML pathogenesis. CONCLUSIONS: The findings of this study suggest whole-exome sequencing as a strong diagnostic genetic tool to identify the causative variants in pediatric MLs. In comparison between oxidative phosphorylation (OXPHOS) and mtDNA maintenance groups, brain stem and periaqueductal gray matter (PAGM) involvement were more commonly seen in OXPHOS group (P value of 0.002 and 0.009, respectively), and thinning of corpus callosum was observed more frequently in mtDNA maintenance group (P value of 0.042).
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ADN Mitocondrial , Mitocondrias , Niño , Humanos , ADN Mitocondrial/genética , Mutación/genética , Cuerpo CallosoRESUMEN
The effectiveness of antimalarial drugs is declining at an ever accelerating rate, with consequent increase in malaria-related morbidity and mortality. The newest antiplasmodial drug from plants is needed to overcome this problem. The aim of this study was to assess antimalarial activity of the ethanolic extracts of 10 different medicinal plants from eight families against Plasmodium falciparum chloroquine-sensitive 3D7 strain. The selection of the hereby studied plants was based on the existing information on their local ethnobotanic history. Plants were dried, powdered, and macerated in a hydroalcoholic solution. Resulting extracts have been assessed for in vitro and in vivo antimalarial and brine shrimp toxicity activities. Of 10 plant species tested, four plants: Althea officinalis L. (Malvaceae), Myrtus communis Linn (Myrtaceae), Plantago major (Plantaginaceae), and Glycyrrhiza glabra L. (Papilionaceae) displayed promising antimalarial activity in vitro (50% inhibitory concentration values of 62.77, 42.18, 40.00, and 13.56 µg/mL, respectively) with no toxicity against brine shrimp larvae. The crude extracts of three active plants, G. glabra, M. communis, and A. officinalis, also significantly reduced parasitemia in vivo in female Swiss albino mice at a dose of 400 mg/kg compared to no treatment. Antiplasmodial activities of extracts of A. officinalis and M. communis are reported for the first time.
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Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Parasitemia/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Plantas Medicinales/química , Plasmodium falciparum/efectos de los fármacos , Animales , Antimaláricos/aislamiento & purificación , Modelos Animales de Enfermedad , Concentración 50 Inhibidora , Irán , Malaria/tratamiento farmacológico , Ratones , Carga de Parásitos , Extractos Vegetales/aislamiento & purificaciónRESUMEN
With the inexorable prevalence and spread of drug-resistant malaria strains, many efforts have been made to find alternative chemotherapeutic agents. In this regard, scientists have developed the concept of hybridization of two or more active pharmacophores into a single chemical compound, resulting in "antimalarial hybrids." The aim of this study was planned based on the highly synergistic effect of the physical hybrid of dihydroartemisinin (DHA) with eosin B (EB). Therefore, a chemical hybrid of the two compounds (DHA-EB) was synthesized, and its antimalarial activity was investigated in vitro and in vivo. The drug hybrid was fabricated through a propionyl ester linker between DHA and EB. The antiplasmodial activity of the new hybrid was tested in vitro on the blood stages of Plasmodium falciparum (chloroquine-sensitive, 3D7 strain) and also evaluated in vivo by Peters' standard test in mice infected with Plasmodium berghei. The hybrid compound was also assessed for in vivo toxicity. Among all the compounds studied, a DHA-EB hybrid showed an appropriate inhibition percentage (53%) was at a very low dose (0.65 nM). The highest in vivo antimalarial activity until the 9th day was related to DHA-EB in a low dose (0.5 mg/kg). Also, the most survival rate was observed in the test group of hybrid compound at a dose of 1.5 mg/kg for 22 days. No external changes were identified in the toxicity assay. The weight of internal organs of treated animals and that of controls indicated nontoxicity of DHA-EB even after 60 days of consumption. In vitro and in vivo studies substantiated that DHA-EB hybrid has the potential for developing as a safe antimalarial drug.