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The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Using exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with myristic acid alkyne (YnMyr) chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), aged 1-50â years, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%) and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%) and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%) and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each) as well as hypertrophy of the clava (24%) were common neuroimaging findings. Acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localization and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-myristoylation was similarly affected in acbd6-deficient zebrafish and X. tropicalis models, including Fus, Marcks and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders.
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Deficiência Intelectual , Microcefalia , Transtornos dos Movimentos , Malformações do Sistema Nervoso , Transtornos do Neurodesenvolvimento , Animais , Feminino , Humanos , Masculino , Transportadores de Cassetes de Ligação de ATP , Deficiência Intelectual/genética , Transtornos dos Movimentos/genética , Malformações do Sistema Nervoso/genética , Transtornos do Neurodesenvolvimento/genética , Tremor , Peixe-Zebra , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Metabolic Syndrome (MetS) is a risk for developing cardiovascular diseases and its prevalence is especially high in psychiatric patients. To date, there is limited data from the United Arab Emirates (UAE) on the prevalence of MetS. Therefore, we aimed to investigate its prevalence and possible risk factors in a large sample of psychiatric patients in the UAE. METHODS: A cross-sectional study was conducted at Al-Ain Hospital, in Al-Ain City, UAE. We collected demographic and clinical data on patients diagnosed with schizophrenia, schizoaffective, and bipolar affective disorder in the period between January 2017 and December 2020. This included their secondary diagnosis (psychiatric or medical), vital signs (heart rate, systolic and diastolic blood pressure, Body Mass Index [BMI]), metabolic parameters (fasting blood glucose, cholesterol, triglycerides, low-density lipoprotein, high-density lipoproteins), and prescribed medications. We used the American Association of Clinical Endocrinology (AACE) criteria to diagnose MetS. RESULTS: We included 889 subjects and of these, 79.8% (N = 709) had a BMI ≥25 kg/m2 and 9.8% (N = 87) had no abnormal metabolic parameters. Overall, 28.1% (N = 250) had MetS with no statistical difference between the three groups. Fasting blood glucose levels and abnormally elevated triglycerides were significant predictors for MetS. CONCLUSION: Our study found that around one in three patients had MetS irrespective of the three diagnoses. Some variables were significant predictors for MetS. Our findings were consistent with other studies and warrant the need for regular screening and management of abnormal metabolic parameters.
There is no statistical difference between schizophrenia, schizoaffective disorder, and bipolar disorder with regards to the prevalence of metabolic syndrome.Fasting blood glucose levels and abnormally elevated triglycerides were significant predictors of metabolic syndrome.Screening of metabolic parameters is important as well as the careful tailoring of the choice of antipsychotics.
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Transtorno Bipolar , Síndrome Metabólica , Transtornos Psicóticos , Esquizofrenia , Humanos , Síndrome Metabólica/epidemiologia , Esquizofrenia/epidemiologia , Transtorno Bipolar/epidemiologia , Masculino , Feminino , Adulto , Estudos Transversais , Prevalência , Pessoa de Meia-Idade , Transtornos Psicóticos/epidemiologia , Fatores de Risco , Emirados Árabes Unidos/epidemiologia , ComorbidadeRESUMO
PURPOSE: The endoplasmic reticulum membrane complex (EMC) is a highly conserved, multifunctional 10-protein complex related to membrane protein biology. In seven families, we identified 13 individuals with highly overlapping phenotypes who harbor a single identical homozygous frameshift variant in EMC10. METHODS: Using exome, genome, and Sanger sequencing, a recurrent frameshift EMC10 variant was identified in affected individuals in an international cohort of consanguineous families. Multiple families were independently identified and connected via Matchmaker Exchange and internal databases. We assessed the effect of the frameshift variant on EMC10 RNA and protein expression and evaluated EMC10 expression in normal human brain tissue using immunohistochemistry. RESULTS: A homozygous variant EMC10 c.287delG (Refseq NM_206538.3, p.Gly96Alafs*9) segregated with affected individuals in each family, who exhibited a phenotypic spectrum of intellectual disability (ID) and global developmental delay (GDD), variable seizures and variable dysmorphic features (elongated face, curly hair, cubitus valgus, and arachnodactyly). The variant arose on two founder haplotypes and results in significantly reduced EMC10 RNA expression and an unstable truncated EMC10 protein. CONCLUSION: We propose that a homozygous loss-of-function variant in EMC10 causes a novel syndromic neurodevelopmental phenotype. Remarkably, the recurrent variant is likely the result of a hypermutable site and arose on distinct founder haplotypes.
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Deficiências do Desenvolvimento , Deficiência Intelectual , Criança , Deficiências do Desenvolvimento/genética , Mutação da Fase de Leitura , Homozigoto , Humanos , Deficiência Intelectual/genética , Proteínas de Membrana/genética , Linhagem , Fenótipo , Convulsões/genéticaRESUMO
Hybrid 3D Finite difference time domain-Monte Carlo ray tracing (FDTD-MCRT) algorithm has been developed to model and optimise small and large scale plasmonically-enhanced luminescent solar concentrator (pLSC) devices for photovoltaic (PV) applications. The configuration parameters (for example, dimensions, shape, and optical properties of metal nanoparticles, luminescent species, and host material) were used to characterise the probability of optical energy transfer and loss processes, as well as reflection, refraction, absorption, emission enhancement, and total internal reflection (TIR) in the pLSC. The algorithm was validated through modelling of various doping concentrations of CdSe/ZnS quantum dots (QD) and gold nano spheres (Au NS) where â¼50% enhancement in optical conversion efficiency (OCE) was observed for a plasmonic composite of 2â ppm Au NS and 0.008 wt. % QD.
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Polarization-sensitive anisotropic plasmonic interaction between gold nanorods (AuNRs) and quantum dots (QDs) encapsulated in an epoxy resin polymer has been experimentally investigated. The anisotropic plasmonic interaction utilized the polarization-dependent plasmonic properties of aligned AuNR in AuNR-QD composite. AuNRs were aligned by an external AC electric field of 3.5 ×105 Vm-1. The plasmonic interaction modified QD absorption and emission dependent on excitation light polarization and maximum enchantment of 10% and 59%, respectively. Moreover, anisotropic plasmonic interaction induced directional emission of QDs has improved emission decay rate by 20% and modulated emission polarization ratio of out-of-plane (vertical) and in-plane (horizontal) from 1 to 0.84.
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A multitude of applications is related to the unique properties of absorption, scattering, and plasmon-enhanced phenomena of metal nanoparticles (MNPs). The aqueous colloidal-based synthesis of MNPs is used more widely as it allows precise shape and size control. However, for various applications, it is required to have the MNPs in an organic solvent or polymer that is compatible with the MNPs. This work establishes a protocol from the synthesis to the phase transfer process of gold nanorods and gold core silver shell nanocuboids (Au@Ag NCs) in dichloromethane. Subsequent dispersion in a polymer (silicone encapsulant polymer) is achieved while retaining the MNPs' plasmonic properties. Au@Ag NCs have not been transferred to an organic solvent to date due to their unique shape and instability in the organic phase. The established protocol is reproducible, and MNPs were found to be stable for up to a year in the polymer. Qualitative and quantitative validation of the experimental results is achieved on MNP concentration by a model based on the finite difference time domain method. Using the model, the concentration of MNPs in nanocomposite can be determined.
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INTRODUCTION: Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare autosomal recessive inborn errors of metabolism characterized by hyperammonemia due to N-acetylglutamate synthase (NAGS) dysfunction. Carglumic acid (Carbaglu®; Orphan Europe Ltd.) is approved by the US Food and Drug Administration (USFDA) for the treatment of hyperammonemia due hepatic NAGS deficiency. Here we report the rationale and design of a phase IIIb trial that is aimed at determining the long-term efficacy and safety of carglumic acid in the management of PA and MMA. METHODS: This prospective, multicenter, open-label, randomized, parallel group phase IIIb study will be conducted in Saudi Arabia. Patients with PA or MMA (≤15 years of age) will be randomized 1:1 to receive twice daily carglumic acid (50 mg/kg/day) plus standard therapy (protein-restricted diet, L-carnitine, and metronidazole) or standard therapy alone for a 2-year treatment period. The primary efficacy outcome is the number of emergency room visits due to hyperammonemia. Safety will be assessed throughout the study and during the 1 month follow-up period after the study. DISCUSSION: Current guidelines recommend conservative medical treatment as the main strategy for the management of PA and MMA. Although retrospective studies have suggested that long-term carglumic acid may be beneficial in the management of PA and MMA, current literature lacks evidence for this indication. This clinical trial will determine the long-term safety and efficacy of carglumic acid in the management of PA and MMA. TRIAL REGISTRATION: King Abdullah International Medical Research Center ( KAIMRC ): (RC13/116) 09/1/2014. Saudi Food and Drug Authority (SFDA) (33066) 08/14/2014. ClinicalTrials.gov (identifier: NCT02426775) 04/22/2015.
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Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Glutamatos/uso terapêutico , Acidemia Propiônica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adolescente , Carnitina/uso terapêutico , Criança , Dieta com Restrição de Proteínas , Esquema de Medicação , Término Precoce de Ensaios Clínicos , Glutamatos/efeitos adversos , Humanos , Metronidazol/uso terapêutico , Estudos Multicêntricos como Assunto , Acidemia Propiônica/terapia , Estudos Prospectivos , Tamanho da Amostra , Arábia SauditaRESUMO
BACKGROUND: Free radicals are small extremely reactive species that have unpaired electrons. Free radicals include subgroups of reactive species, which are all a product of regular cellular metabolism. Oxidative stress happens when the free radicals production exceeds the capacity of the antioxidant system in the body's cells. OBJECTIVE: The current review clarifies the prospective role of antioxidants in the inhibition and healing of diseases. METHODS: Information on oxidative stress, free radicals, reactive oxidant species, and natural and synthetic antioxidants was obtained by searching electronic databases like PubMed, Web of Science, and Science Direct, with articles published between 1987 and 2023 being included in this review. RESULTS: Free radicals exhibit a dual role in living systems. They are toxic byproducts of aerobic metabolism that lead to oxidative injury and tissue disorders and act as signals to activate appropriate stress responses. Endogenous and exogenous sources of reactive oxygen species are discussed in this review. Oxidative stress is a component of numerous diseases, including diabetes mellitus, atherosclerosis, cardiovascular disease, Alzheimer's disease, Parkinson's disease, and cancer. Although various small molecules assessed as antioxidants have shown therapeutic prospects in preclinical studies, clinical trial outcomes have been inadequate. Understanding the mechanisms through which antioxidants act, where, and when they are active may reveal a rational approach that leads to more tremendous pharmacological success. This review studies the associations between oxidative stress, redox signaling, and disease, the mechanisms through which oxidative stress can donate to pathology, the antioxidant defenses, the limits of their effectiveness, and antioxidant defenses that can be increased through physiological signaling, dietary constituents, and probable pharmaceutical interference. Prospective clinical applications of enzyme mimics and current progress in metal- and non-metal-based materials with enzyme-like activities and protection against chronic diseases have been discussed. CONCLUSION: This review discussed oxidative stress as one of the main causes of illnesses, as well as antioxidant systems and their defense mechanisms that can be useful in inhibiting these diseases. Thus, the positive and deleterious effects of antioxidant molecules used to lessen oxidative stress in numerous human diseases are discussed. The optimal level of vitamins and minerals is the amount that achieves the best feed benefit, best growth rate, and health, including immune efficiency, and provides sufficient amounts to the body.
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BACKGROUND: The number of coronavirus disease-19 (COVID-19) positive patients and fatalities keeps rising. It is important to recognize risk factors for severe outcomes. Evidence linking vitamin D deficiency and the severity of COVID-19 is tangential but substantial - relating to race, obesity, and institutionalization. OBJECTIVE: This study aims to examine the function of vitamin D and nutritional defense against infections such as COVID-19, which is the goal of this research. METHODS: This study includes observational cohort, cross-sectional, and case-control studies that estimated variances in serum levels of vitamin D among patients with mild or severe forms of COVID-19, and in patients who died or were discharged from hospitals. Studies that assessed the risk of developing severe disorder or death in patients with vitamin D deficiency, defined as levels of vitamin D< 20 ng/mL, were also encompassed. RESULTS: In a retrospective study on 464,383 individuals, results showed that individuals who had the highest risks for severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection, and for COVID-19 severity when infected, had vitamin D levels < 30 nmol/L; Odds Ratio (OR) were 1.246 [95% Confidence Interval (CI): 1.210-1.304] and 1.513 [95%CI: 1.230-1.861], respectively. Additionally, in a retrospective observational study of 191,779 individuals in the USA. The SARS-CoV-2 positivity rate was greater in the 39,190 subjects with vitamin D < 20 ng/mL [12.5%, 95% C.I. 12.2-12.8%] than in the 27,870 subjects with sufficient serum vitamin D levels [8.1%, 95% C.I. 7.8-8.4%] and in the 12,321 subjects with serum vitamin D ⩾ 55 ng/mL [5.9%, 95% C.I. 5.5-6.4%]. CONCLUSION: People hospitalized for COVID-19 should be checked for vitamin D status and supplemented, and high-dose-in testing should be considered in the recovery trial. More importantly, screening for malnutrition and the administration of the best nutritional supplements are essential for the immune system of the human body to function as it should be. Thus, nutritional supplementation is crucial for people with risk factors as well as older adults with compromised immune systems.
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COVID-19 , SARS-CoV-2 , Índice de Gravidade de Doença , Deficiência de Vitamina D , Vitamina D , Humanos , Estudos de Casos e Controles , COVID-19/sangue , Estudos Transversais , Progressão da Doença , Estudos Retrospectivos , Fatores de Risco , Vitamina D/sangue , Deficiência de Vitamina D/sangueRESUMO
The risk of metabolic syndrome (MetS) has been attributed to antipsychotic use in psychiatric patients. To date, there is limited data on the relationship between antipsychotic polypharmacy and MetS in patients with schizophrenia, schizoaffective disorder and bipolar disorder. Therefore, we aimed to investigate the rate of MetS in patients with these disorders receiving antipsychotic monotherapy and polypharmacy. We conducted a cross-sectional study on patients seen between January 2017 and December 2020, collecting data on the class, type, route of administration and number of antipsychotics received. We used the American Association of Clinical Endocrinology criteria to diagnose MetS. We included 833 subjects of whom 573 (68.8%) received antipsychotic monotherapy and 260 (31.2%) received polypharmacy. Overall, 28.6% ( N â =â 238) had MetS with no statistical difference between the two groups. Diastolic blood pressure and receiving olanzapine were significant predictors for developing MetS. In conclusion, our study found no significant difference in the rate of MetS between antipsychotic monotherapy and polypharmacy. A number of variables were significant predictors for MetS. Our findings were consistent with other studies and warrant the need for careful choice of antipsychotics and regular screening and management of abnormal metabolic parameters.
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Antipsicóticos , Transtorno Bipolar , Síndrome Metabólica , Polimedicação , Transtornos Psicóticos , Esquizofrenia , Humanos , Antipsicóticos/uso terapêutico , Antipsicóticos/efeitos adversos , Esquizofrenia/tratamento farmacológico , Feminino , Masculino , Transtorno Bipolar/tratamento farmacológico , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/induzido quimicamente , Estudos Transversais , Adulto , Transtornos Psicóticos/tratamento farmacológico , Pessoa de Meia-IdadeRESUMO
Introduction: Cardiovascular diseases are the main cause of death among type 2 diabetic patients. Higher levels of plasminogen activator urokinase receptor have been found to predict morbidity and mortality across acute and chronic diseases in the common populace. This study aims to explore the role of serum plasminogen activator urokinase receptor levels as a cardiometabolic risk factor among type 2 diabetic Iraqi patients. Methods: Seventy type 2 diabetic patients (40 male and 30 female) (mean age: 46.20±7.56 years) participated in this study; 35 patients were with cardiovascular disease and 35 were without cardiovascular disease; their ages range was 40-55 years. In addition, 30 individuals who apparently healthy were selected as the control group. Results: There were significant increases (P<0.05) in glycemic and lipid profiles in diabetic patients with cardiovascular disease as compared to those without cardiovascular disease and control group. The present results reveal high levels of plasminogen activator urokinase receptor (2500.72±12.36 ρg/mL versus 2255.32±10.15 ρg/mL) with OR=1.80, 95%CI 1.2, and P=0.0001 in type 2 diabetic patients with and without cardiovascular disease respectively as compared to healthy control (229.00±14.48 ρg/mL). Conclusion: It has been concluded that serum plasminogen activator urokinase receptor showed higher levels among type 2 diabetic patients with cardiovascular disease, this revealed it's critical role in cardiac disease. Therefore, it could be considered a more sensitive biomarker for the detection of cardiovascular events among type 2 diabetic patients who were at high-risk.
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Physical examination is a core component of any assessment done by a physician. Despite that, a physical examination is not always a top priority in many patients with psychiatric illnesses. We present the case of a woman with a prior diagnosis of a delusional disorder with overinvested religious beliefs. The patient had been stable on treatment for many years and only recently presented with a physical complaint, and manifestation assumed to be due to the nature of her psychiatric illness and, hence, overlooked by many physicians before being examined by her last psychiatrist. This resulted in a significant mobility problem for the patient. The patient showed partial insight, linking her pain to a "message from God." Despite the delusional context, the psychiatrist was allowed to examine her feet and discovered significant neglect and poor foot hygiene. This case emphasizes the importance of conducting thorough physical examinations in psychiatric settings. Moreover, it presents an example of situations preventing psychiatric patients from being examined despite displaying obvious physical signs.
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The indiscriminate use of antibacterial agents has resulted in one of the largest recent global health problems, which is the emergence of bacterial resistance. This study aimed to examine the antimicrobial and antioxidant activities of ethanolic extracts of the two medicinal plants; Rosmarinus officinalis pods and Thymus vulgaris leaves on Escherichia coli urinary isolates. Both plants were extracted by absolute ethanol, and various concentrations (100, 50, 25, and 12.5 mg/ml) of the ethanolic extracts were prepared and tested against 53 urinary isolates of E. coli. An antibiotic susceptibility test was performed using chloramphenicol, gentamycin, amoxicillin, ceftriaxone, and ciprofloxacin against isolated bacteria. The antioxidant activity was measured using the DPPH method. The chemical analysis of both extracts was determined using gas chromatography-mass spectrometry (GC/MS) technique. The results showed that 88.7% of the isolated bacteria were sensitive to chloramphenicol and 87% were sensitive to gentamycin, while all isolates were resistant to amoxicillin, 13% of E. coli isolates were found to be multidrug-resistant (MDR). The inhibitory zone of R. officinalis extract against E. coli ranged between 8 and 23 mm and for T. vulgaris extract ranged between 8 and 20 mm at concentrations between 25, 50, and 100 mg/ml. The MIC of both extracts against isolates is between 12.5 and 50 mg/ml, while the MBC is between 50 and 100 mg/ml. The DPPH radical scavenging potential of T. vulgaris was 83.09%, followed by R. officinalis (81.26%). The chemical analysis by GC-MS of R. officinalis showed that the most active compounds were: eucalyptol (18.57%), bicycloheptan (10.01%), and octahydrodibenz anthracene (7.44%) and for T. vulgaris the most active compounds were: thymol (5.7%), phytol (7.92%), and hexadecanoic acid (18.51%). R. officinalis and T. vulgaris ethanolic extracts possessed antimicrobial and antioxidant activities and were found to be rich natural sources of active constituents used as traditional medicine.
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Human Cytomegalovirus (HCMV) is a leading healthcare problem associated with stillbirth and congenital abnormalities. Determining the seroprevalence and the possible risk factors related to HCMV infections may be a cornerstone in preventing its complications. This cross-sectional study was conducted in Kassala and River Nile States to determine the seroprevalence and risk factors associated with HCMV infection in pregnant women. One hundred eighty-four (n = 184) blood specimens were collected from pregnant women from February 2018 to January 2020. Enzyme-linked immunosorbent assay (ELISA) was used to detect HCMV-specific IgG and IgM antibodies. Socio-demographical characteristics of the women were collected using structured questionnaires. The results showed that HCMV IgG was detected in 170 (92.4%) of the blood specimens, and IgM was detected in 29/93 (31.2%). There was a significant relationship between the history of miscarriage and the presence of IgG and IgM with a p-value = 0.001 and between HCMV IgM and gestational stage (p-value = 0.028). The study found a strikingly high seroprevalence of HCMV infections among pregnant women in the investigated States. This high percentage of illiterate housewives living in rural areas makes it possible to reduce the incidence of HCMV infection in pregnant women by improving their knowledge, attitude, and practice regarding the route of viral transmission, which may reflect in lowering the rate of congenital diseases in their infants.
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Infecções por Citomegalovirus , Gestantes , Gravidez , Lactente , Humanos , Feminino , Sudão , Estudos Transversais , Estudos Soroepidemiológicos , Infecções por Citomegalovirus/epidemiologia , Anticorpos Antivirais , Imunoglobulina G , Imunoglobulina MRESUMO
BACKGROUND: Pulmonary aspergillosis is a lung infection caused by Aspergillus spp., which can cause severe illnesses in immunocompromised patients with underlying lung disease or who have asthma and inhale their spores. This study aimed to screen the antifungal susceptibility of Aspergillus spp. isolated from patients with underlying pulmonary infections and characterize the isolates using PCR and sequencing. METHOD: Three hundred and eighty-four sputum or bronchoalveolar lavage samples were collected and processed for the isolation and identification, and characterization of Aspergillus species and molecular amplification of the ITS1-5.8S-ITS2 region by the PCR and Sanger sequencing method. Antifungal susceptibility tests for itraconazole and voriconazole were performed using the E-test. RESULT: The overall results revealed that out of 384 patients, 32 (8.3%) were positive for fungal growth, including 28 (87.5%) Aspergillus spp. The highest resistance rate (100 and 44.4%) was obtained from itraconazole against A. niger and A. fumigatus. In contrast, voriconazole revealed the best activities against all tested fungi compared to itraconazole. All A. flavus were sensitive to voriconazole, while only 54.5% were sensitive to itraconazole. The MICs of E-test for Aspergillus spp were 1.6 ± 1.8 and 0.6 ± 0.93 for itraconazole and voriconazole, respectively. CONCLUSIONS: The prevalence of aspergillosis was high, with a significant association with underlying lung diseases. Voriconazole was the drug of choice for isolated fungi.
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Background: Cytomegalovirus (CMV) is the most common opportunistic pathogen among renal transplants with significant morbidity and mortality. This study was designed to detect CMV DNA and to determine the frequency of different glycoprotein B (UL55) genotypes among Sudanese renal transplant recipients. Methods: One hundred and four renal transplant recipients were included in this study. A blood specimen was collected from each recipient. DNA was extracted from plasma using the QIAamp DNA mini kit. CMV amplification and quantification were performed using CMV Real-RT Quant kits. Genotyping of human CMV gB was carried out by nested PCR and sequencing of the highly diverse region of gB. Results: CMV DNA was detected in 40/104 (38.5%) of renal transplant recipients. The average of the CMV DNA viral load was 358 × 104 copies/ml (6.5 log10) ranging from 62 copies/ml (1.8 log10) to 1.43 × 108 copies/ml (9 log10). CMV viremia was detected in 60% of recipients of less than 1-12 months, 17% of 13-24, 10% of 25-36, 5% of 37-48, and 8% in more than 48 months posttransplantation with no association (p = 0.296) between CMV viremia and postrenal transplantation time. The association between the type of immunosuppressive drugs and high viral loads (>1000 copies/ml) showed a significant difference (p = 0.05). The association between CMV loads of >1000 copies/ml and symptoms of CMV disease was highly significant (p ≤ 0.001). Fever 7 (41%), fever and leucopenia 6 (35%), and gastrointestinal disease 4 (24%) were the most common symptoms of CMV disease. CMV genotyping revealed 8 cases (80%) for gB3 and 2 cases (20%) for gB4 genotypes. The most frequent genotype among Sudanese renal transplant recipients was gB3. Conclusions: The frequency of CMV DNA is high among Sudanese renal transplant recipients. CMV gB3 is the most predominant glycoprotein B genotype in Sudanese renal transplant recipients.
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Infecções por Citomegalovirus , Transplante de Rim , Citomegalovirus/genética , Infecções por Citomegalovirus/complicações , DNA Viral/genética , Genótipo , Humanos , Transplante de Rim/efeitos adversos , Transplantados , Proteínas do Envelope Viral/genética , Carga Viral , ViremiaRESUMO
Normal thyroid hormone level is essential to maintain the normal physiologic function of the human body. Disturbances of these hormone levels have variable clinical manifestations ranging from asymptomatic to severe illness. Resistance to thyroid hormone (RTH) is a syndrome characterized by reduced intracellular action of T3, the active thyroid hormone. It is a rare autosomal dominant condition and occurs mostly due to heterogeneous mutations in the thyroid hormone receptor. Other causes of RTH include thyroid hormone cell membrane transport defect and thyroid hormone metabolism defect. Affected individuals present with symptoms of both increased and decreased thyroid hormone action, depending on the tissue's predominant receptor isoform expression, the magnitude of hormonal resistance, and the effectiveness of compensatory mechanisms. Here, we share our experience in diagnosing a case of RTH confirmed with a genetic test and found to have sequence variant mutation that is not well described in the literature previously due to the absence of genetic conclusive evidence.
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BACKGROUND: Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare, autosomal recessive inborn errors of metabolism that require life-long medical treatment. The trial aimed to evaluate the effectiveness of the administration of carglumic acid with the standard treatment compared to the standard treatment alone in the management of these organic acidemias. METHODS: The study was a prospective, multicenter, randomized, parallel-group, open-label, controlled clinical trial. Patients aged ≤ 15 years with confirmed PA and MMA were included in the study. Patients were followed up for two years. The primary outcome was the number of emergency room (ER) admissions because of hyperammonemia. Secondary outcomes included plasma ammonia levels over time, time to the first episode of hyperammonemia, biomarkers, and differences in the duration of hospital stay. RESULTS: Thirty-eight patients were included in the study. On the primary efficacy endpoint, a mean of 6.31 ER admissions was observed for the carglumic acid arm, compared with 12.76 for standard treatment, with a significant difference between the groups (p = 0.0095). Of the secondary outcomes, the only significant differences were in glycine and free carnitine levels. CONCLUSION: Using carglumic acid in addition to standard treatment over the long term significantly reduces the number of ER admissions because of hyperammonemia in patients with PA and MMA.
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Erros Inatos do Metabolismo dos Aminoácidos , Acidemia Propiônica , Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Glutamatos , Humanos , Ácido Metilmalônico , Acidemia Propiônica/tratamento farmacológico , Estudos ProspectivosRESUMO
The aim of the present work entitled electronic structure of PVA-PEG-Y2O3 (54 atom) is to present a theoretical study based on the hybrid function of three parameters Lee-Yang-Parr B3LYP of the density functional theory "DFT" quantum mechanical approach together with LanL2DZ basis sets for optoelectronics applications. The geometric properties included improving geometric optimization (bonds and angles), as electronics properties include ionization potential, electron affinity, chemical hardness, chemical softness, electronegativity, total energy, cohesive energy, energy gap, electrophilicity, and density states, in addition to the spectral properties that involved IR, Raman, and UV-Visible. The results showed that the LanL2DZ basis sets are efficient strongly suggested for heavy metals and give good relax for the structure. The results state that the yttrium oxide has low LUMO-HOMO energy gap, and they have more biological activity ratios. The obtained results indicated that the PVA-PEG-Y2O3 can be used in different fields for electronics and photonics applications such as sensors, transistors, diodes, solar cell, electronic gates, and lasers.
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Novel poly(vinyl alcohol) (PVA) based soft gels with luminescent properties are detailed in this contribution. Lanthanide complex of terbium ions with anthranilic acid, Tb(ant)3·2H2O, was synthesized and incorporated into a DMSO/water solution, followed by addition of PVA, to attain soft gels at room temperature. Morphological and thermal analyses revealed homogeneous distribution of Tb(ant)3·2H2O into the PVOH/DMSO/water gel, and that incorporation of the terbium complex does not alter the thermal properties of the gels. The gels are transparent and luminescent, as they exhibit Large Stokes shift down shifting (LSS DS) up to 400nm, with very high emission quantum yield, that was found to be function of Tb complex concentration.