Diagnosis of metaphyseal fractures in infants and young children with suspected inflicted injury: a systematic review of cross-sectional imaging techniques.

AIM: To compare the diagnostic accuracy, advantages, and disadvantages of different medical imaging techniques for detecting metaphyseal fractures (also known as classic metaphyseal lesions [CMLs]) in infants and young children with suspected inflicted trauma. MATERIALS AND METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool criteria. Predefined keywords were used to search online databases for English articles published between 1 January 1980 and 31 March 2023. RESULTS: The initial search revealed 83 studies, only five of which met the inclusion criteria. The sensitivity and specificity of positron-emission tomography (PET) were 67% and 99%, respectively. The sensitivity and specificity of ultrasound were 55-61% and 96-97%, respectively. The sensitivity of magnetic resonance imaging (MRI) whole-body screening was 31%. The sensitivity of bone scintigraphy was 17% in one and 35% in a second study. Computed tomography was not used to detect CMLs in any diagnostic accuracy study. CONCLUSION: This systematic review has identified only a small number of relevant studies. In addition to the skeletal survey, PET and ultrasound may be helpful for the diagnosis of CMLs in infants and young children with suspected abuse; however, ultrasound has greater potential than PET due to its higher specificity, lack of radiation exposure, low cost, and wider availability.

Determining the 3-substituted Coumarins inhibitory potential against the HslV protease of E. coli.

OBJECTIVE: The growing bacterial resistance towards classical antibiotics demands the development of novel approaches for the effective treatment of potentially fatal bacterial infections in humans. Proteostasis is crucial for the survival of every living cell, as several important physiological functions depend on well-regulated proteostasis. Within bacteria, the regulation of proteostasis relies on AAA+ (Adenosine 5'-triphosphatases associated with diverse cellular activities), ATPases, such as the HslVU complex (heat shock locus gene products U and V), along with other proteases. The HslVU protease/chaperon complex is thought to be the progenitor of the eukaryotic proteasome that regulates proteostasis mostly in prokaryotes. This study aimed to determine the inhibitory potential of 3-substituted coumarin derivatives against Escherichia coli heat shock locus V (HslV) protease. MATERIALS AND METHODS: In this study, twenty-three derivatives of 3-substituted coumarin were assessed for their inhibitory potential against E. coli HslV protease using both in-vitro and in-silico techniques. RESULTS: Among all the tested compounds, US-I-64, US-I-66, US-I-67, and US-I-68 displayed notable inhibitory potential against the HslV protease, showing IC50 (half maximal inhibitory concentration) values ranging from 0.2 to 0.73 µM. Additionally, the inhibitory potential of these compounds against the eukaryotic proteasome was also evaluated using a separate in-silico study. It was found that these compounds did not bind with the proteasomal active site, suggesting no apparent side effects of these lead molecules. CONCLUSIONS: These identified HslV protease inhibitors can be used for the development of novel and safer anti-bacterial drugs.

Exploring the Traditional Chinese Medicine (TCM) database chemical space to target I7L protease from monkeypox virus using molecular screening and simulation approaches.

In the current study, we used molecular screening and simulation approaches to target I7L protease from monkeypox virus (mpox) from the Traditional Chinese Medicines (TCM) database. Using molecular screening, only four hits TCM27763, TCM33057, TCM34450 and TCM31564 demonstrated better pharmacological potential than TTP6171 (control). Binding of these molecules targeted Trp168, Asn171, Arg196, Cys237, Ser240, Trp242, Glu325, Ser326, and Cys328 residues and may affect the function of I7L protease in in vitro assay. Moreover, molecular simulation revealed stable dynamics, tighter structural packing and less flexible behaviour for all the complexes. We further reported that the average hydrogen bonds in TCM27763, TCM33057, TCM34450 and TCM31564I7L complexes remained higher than the control drug. Finally, the BF energy results revealed -62.60 ± 0.65 for the controlI7L complex, for the TCM27763I7L complex -71.92 ± 0.70 kcal/mol, for the TCM33057I7L complex the BF energy was -70.94 ± 0.70 kcal/mol, for the TCM34450I7L the BF energy was -69.94 ± 0.85 kcal/mol while for the TCM31564I7L complex the BF energy was calculated to be -69.16 ± 0.80 kcal/mol. Although, we used stateoftheart computational methods, these are theoretical insights that need further experimental validation.

Halogens engineering-based design of agonists for boosting expression of frataxin protein in Friedreich's ataxia.

OBJECTIVE: Decreased expression of the mitochondrial protein frataxin is the cause of the neurodegenerative disorder Friedreich's ataxia. In patients with cardiac disorders, the death rate of this disease is very high, up to 66%. In order to combat Friedreich ataxia, which is a potentially toxic disorder, de novo drug discovery and design have been created utilizing the approach of compound engineering with halogens. This study aimed to investigate the potential for effective treatment of Friedreich ataxia. MATERIALS AND METHODS: The screening of twenty different agonist compounds was carried out in order to find the most promising agonist compound that may be used for molecular docking prediction against the Frataxin Protein. The compound with the lowest binding energies is then optimized by halogens. The final candidate's drug-like properties are identified through Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling. Lipinski's rule of five was checked. Molecular dynamic stimulations were evaluated. RESULTS: The most potent agonist compound was identified out of twenty different compounds utilizing a docking approach against the Frataxin Protein. The compound with the lowest binding energies was next subjected to optimization by halogens. The optimized agonist 9-[1-[(1S, 5R)-8, 8-dimethyl-8-azoniabicyclo[3.2.1]octan-3-yl]triazol-4-yl]fluoren-9-ol  has higher binding energy of -10.4Kcal/mol with molecular weight of 705.63 g/mol. Drug-like properties are identified through ADMET profiling, having water solubility of about -7.59, skin permeation -7.08 cm/s, bioavailability score 0.17, and high GI absorption. The candidate fulfills the Lipinski rule of five and portrays efficient molecular dynamic stimulations. CONCLUSIONS: The selected agonist is one of the most potent compounds in increasing Frataxin protein expression. Furthermore, optimization with halogens can be a productive approach to improve the candidate's drug efficacy. The development of effective medications for the treatment of Friedreich ataxia would be aided by the results of these computational investigations.

Antileishmanial effects, cellular mechanisms, and cytotoxicity of Elettaria cardamomum essential oil against Leishmania major infection.

Leishmaniasis is an infectious disease with various clinical manifestations. We studied the therapeutic effects of Elettaria cardamomum essential oil (ECEO) against Leishmania major infection. In vitro effects of ECEO against L. major were examined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and macrophage assays. Nitric oxide (NO) production, infection inhibition in macrophages, and the apoptotic activity of ECEO in treated parasites were also measured. By calculating the 50% cytotoxic concentrations (CC50), we studied the cytotoxicity effects of ECEO on human macrophage cells (THP-1). The efficacy of ECEO for improving cutaneous leishmaniasis (CL) lesions in mice (BALB/c) was determined by evaluating the size of lesions and the number of amastigotes before and after four weeks of treatment. The effects of ECEO on liver and kidney function in the tested mice were also evaluated. ECEO dose-dependently (p<0.001) inhibited the viability and the mean number of promastigotes and amastigote forms of L. tropica. Four weeks of treatment with ECEO at the doses of 2.5 and 5 mg/kg/ day significantly (p<0.001) improved the CL lesions and reduced the number of parasites in the infected mice. ECEO significantly increased NO production, apoptosis induction, and infection rate in parasites. The CC50 value for ECEO and MA was 303.4 µg/mL and 835.2 µg/mL, respectively. In the mice receiving ECEO at the doses of 2.5 and 5 mg/kg/day for 28 days, no significant change was reported between the serum level of liver enzymes and kidney factors when compared with the control group. ECEO displayed promising efficacy in parasite reduction in vitro and in the animal model. ECEO can thus be used as an alternative medicine to treat CL.

Study on development and tissue permeation of different formulations of Fasudil.

OBJECTIVE: The study is intended to formulate Fasudil loaded vesicular system for application in the management of angina. MATERIALS AND METHODS: Fasudil was made into a complex with phospholipid, and other different formulations were made, including Fasudil solution, liposomal form, and Fasudil loaded into the gel. A drug characterization study was conducted and noted. Drug release was quantified and analyzed and, finally, inoculated in Sprague-Dawley rats. These rats underwent anginal induction, and each formulation's effect on angina was evaluated. RESULTS: Drug solution (F-Phos) and F-Phos-Lipo (liposomal dispersion form of the drug) have shown that more than half percent of them have been released within 1.5 hours, and the rapid release occurred from liposomal dispersion in the first hour. The study determined the viscosity of the different formulations, which was significantly (p<0.05) higher than the theoretical sum of the viscosity of each formulation. The study found that the F-Phos-Lipo+P-407HMS formulation is the most effective as its application has the minimum infarct area percentage compared to the other formulations and can also reduce creatine kinase levels significantly as compared to the different formulations (p<0.05). CONCLUSIONS: The study concluded that the typical gel formulation (liposomal Fasudil dispersed in hydroxypropyl methylcellulose solution, which is added to blank poloxamer 407) had been shown to have significantly anti-anginal properties, including easy administration, its application on the infarct area percentage and subsequently its pharmacological effect on the cardiac tissue.

A one-health approach to design an mRNA-based vaccine candidate against the lumpy skin disease virus as an alternative to live-attenuated vaccines.

OBJECTIVE: Recently, lumpy skin disease (LSD) has been spread over the Asian, European, and Middle Eastern regions making it a significant hazard to the chain of cattle production, milk production, and human milk consumption, requiring prompt attention. Lumpy skin disease virus has high morbidity and low fatality rates, but its infections have led to terrible economic and agricultural consequences. Although live-attenuated vaccines have been commercialized, farmers in different regions have not taken them well because of the allergic responses against the vaccines. The study aims to develop an mRNA-based vaccine candidate for LSDV, using immunoinformatic approaches to minimize allergenicity and homology while maximizing immunogenic potential. MATERIALS AND METHODS: The study used extensive immunoinformatic approaches to shortlist five proteins from the LSDV genome that belong to the transmembrane region and are crucial in early viral interaction with host cells. The B-cell and T-cell-specific epitopes were chosen based on non-allergenicity, antigenicity, non-homology, surface accessibility, and lower IC50 inhibition values. The construct's stability, hydrophilicity, and antigenic potential were analyzed using the instability index, Grand Average of Hydropathicity (GRAVY) index, and antigenicity, respectively. RESULTS: We selected a total of 34 epitopes, consisting of 12 B-cell-specific epitopes and 22 T-cell-specific epitopes. These epitopes were chosen based on their characteristics such as non-allergenicity, antigenicity, non-homology, surface accessibility, and lower IC50 inhibition values. Specifically, 11 epitopes were selected for Major Histocompatibility Complex-I, and another 11 epitopes were chosen for Major Histocompatibility Complex-II. The inclusion of the RS09 adjuvant enhanced the immunogenic potential of the vaccine. The instability index was found to be 38.60. Additionally, the GRAVY index, indicating hydrophilicity, was calculated as -0.151. Furthermore, the antigenicity value of 0.6073 confirmed its potential to elicit an immune response. Further supporting its immunogenic potential, strong immune stimulation was observed, with IgM+IgG titers reaching 6,000 (arbitrary units) and IFNg titers measuring 400,000 ng/mL. These results provide additional evidence of the vaccine's ability to stimulate a robust immune response. CONCLUSIONS: The study results indicate that the developed mRNA-based vaccine candidate for LSDV has high immunogenic potential and could serve as an effective alternative to live-attenuated vaccines. Further experimental validations are required to test its efficacy. The study also highlights the potential of the One-Health approach to tackle non-zoonotic diseases that have significant consequences for the environment and humanity.

Side chain inset of neurogenerative amino acids to metalloproteins: a therapeutic signature for huntingtin protein in Huntington's disease.

OBJECTIVE: Huntington's disease is a dominant autosomal inherited neurodegenerative disease that results in progressive impairment, characterized by dementia, chorea, and behavioral and cognitive decline. The objective of this study was to investigate the potential activity of metalloproteins against the huntingtin protein using various insertion-based engineering computational methods. Metalloproteins, metal protein complexes involved in important biochemical and physiological processes, were explored as potential drug candidates for Huntington's disease. MATERIALS AND METHODS: A total of 18 metalloproteins were selected as drug candidates and studied to assess their potential inhibitory effects on the huntingtin protein. The screening process was based on the lowest binding energy. The metalloprotein with the lowest docking score was chosen for side chain insertion of neurogenerative amino acids. The engineered metalloprotein was then evaluated based on physiochemical properties, allergenicity, toxicity, and surface accessibility. Cloning and expression analysis was performed to further investigate its potential as a therapeutic agent. RESULTS: The metalloprotein chosen for side chain insertion, cytochrome C oxidase, showed promising results. It was computed as a probable non-allergen and exhibited no toxic domains, indicating its non-toxic nature. Additionally, it demonstrated a strong binding affinity with the huntingtin protein, with a binding energy of -1,253.3 Kcal/mol. CONCLUSIONS: Metal-based proteins, when engineered with additional neurogenerative amino acids, hold potential as drug candidates for treating neurodegenerative diseases such as Huntington's disease. The successful development of these engineered metalloproteins could offer therapeutic advantages. Further testing, both in vitro and in vivo, is necessary to evaluate their efficacy and validate their potential activity as novel drugs for the treatment of neurodegenerative diseases.

A pharmacophore screening approach of homeopathic phenols for a renovated design of fragment-optimized Bauhiniastatin-1 as a drug against acromegaly.

OBJECTIVE: Acromegaly is a fatal and chronic disease that is caused by the abnormal secretion of growth hormone (GH) by the pituitary adenoma or pituitary tumor, resulting in an increased circulated concentration of insulin-like growth factors 1 (IGF-1), where in most of the cases it is secreted by a pituitary tumor. Higher levels of GH cause an increase in IGF-1 in the liver leading to multiple conditions such as cardiovascular diseases, glucose imbalance, cancer, and sleep apnea. Medical treatments such as surgery and radiotherapy can be used as the first choice of patients; however, specified human growth hormone control should be an essential treatment strategy due to an incidence rate of 0.2-1.1 yearly. Therefore, the main focus of this study is to develop a novel drug for treating acromegaly by exploiting medicinal plants that have been screened using phenol as a pharmacophore model to identify target therapeutic medicinal plant phenols. MATERIALS AND METHODS: The screening identified thirty-four pharmacophore matches of medicinal plant phenols. These were selected as suitable ligands and were docked against the growth hormone receptor to calculate their binding affinity. The candidate with the highest screened score was fragment-optimized and subjected to absorption, distribution, metabolism, and excretion (ADME) analysis, in-depth toxicity predictions, interpretation of Lipinski's rule, and molecular dynamic simulations to check the behavior of the growth hormone with the fragment-optimized candidate. RESULTS: The highest docking energy was calculated as -6.5 K/mol for Bauhiniastatin-1. Enhancing the performance of Bauhiniastatin-1 against the growth hormone receptor with fragment optimization portrayed that human growth hormone inhibition can be executed in a more efficient and better way. Fragment-optimized Bauhiniastatin-1 (FOB) was predicted with high gastrointestinal absorption, a water solubility of -2.61 as soluble, and synthetic accessibility of 4.50, achieving Lipinski's rule of 5, with low organ toxicity prediction and interpreting a positive behavior against the targeted protein. The discovery of a de novo drug candidate was confirmed by the docking of fragment-optimized Bauhiniastatin-1 (FOB), which had an energy of -4,070 Kcal/mol. CONCLUSIONS: Although successful and completely harmless, present healthcare treatment does not always eradicate the disease in some individuals. Therefore, novel formulas or combinations of currently marketed medications and emergent phytochemicals will provide new possibilities for these instances.

Revolutionizing treatment for toxic shock syndrome with engineered super chromones to combat antibiotic-resistant Staphylococcus aureus.

OBJECTIVE: Staphylococcus aureus-induced toxic shock syndrome (TSS) is a rare, but potentially fatal disease with limited treatment options. The emergence of antibiotic-resistant strains has led to a pressing need for the development of effective therapies. This study aimed to identify and optimize potential drug candidates against toxic shock syndrome by targeting the pathogenic toxin protein using chromones as lead compounds. MATERIALS AND METHODS: In this study, 20 chromones were screened for their ability to bind to the target protein. The top compounds were further optimized through the addition of cycloheptane and amide groups, and the resulting compounds were evaluated for their drug-like properties using chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling. RESULTS: Among the compounds screened, 7-Glucosyloxy-5-hydroxy-2-[2-(4-hydroxyphenyl) ethyl] chromone exhibited the highest binding affinity with a molecular weight of 341.40 g/mol and a binding energy of -10.0 kcal/mol. The optimized compound exhibited favorable drug-like properties, including high water solubility, synthetic accessibility, skin permeation, bioavailability, and gastrointestinal absorption. CONCLUSIONS: This study suggests that chromones can be engineered to develop effective drugs against TSS caused by S. aureus. The optimized compound has the potential to be a promising therapeutic agent for the treatment of TSS, providing new hope for patients suffering from this life-threatening disease of toxic shock syndrome.

The association between hypertension and glucose tolerance among adults with prediabetes in Hail City, Saudi Arabia.

OBJECTIVE: As a worldwide epidemic, the frequency of prediabetes is rapidly increasing. As a result, the present study investigated pre-diabetes synergistic factors in the Saudi population. PATIENTS AND METHODS: This descriptive study used samples from 31 Hail-area primary health clinics (PHCs). Participants were chosen at random from December 2021 to June 2022. RESULTS: There were 164 participants in this study, of which 86 males (52.4%) and 78 females (47.6%). The GTT revealed that none of the study participants had diabetes, but an A1C test revealed that all of them had A1C levels above 6.5%. Approximately 16/86 (18.6%) of the 86 men were overweight, whereas 53/86 (61.6%) were obese. CONCLUSIONS: Saudi Arabia's prediabetes rate has increased due to obesity/overweight, family history of diabetes, heart rate variability, and poor sleep quality. HbA1c screening should replace GTT to prevent progression to T2DM.

Antileishmanial effects, cellular mechanisms, and cytotoxicity of Elettaria cardamomum essential oil against Leishmania major infection

@#Leishmaniasis is an infectious disease with various clinical manifestations. We studied the therapeutic effects of Elettaria cardamomum essential oil (ECEO) against Leishmania major infection. In vitro effects of ECEO against L. major were examined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and macrophage assays. Nitric oxide (NO) production, infection inhibition in macrophages, and the apoptotic activity of ECEO in treated parasites were also measured. By calculating the 50% cytotoxic concentrations (CC50), we studied the cytotoxicity effects of ECEO on human macrophage cells (THP-1). The efficacy of ECEO for improving cutaneous leishmaniasis (CL) lesions in mice (BALB/c) was determined by evaluating the size of lesions and the number of amastigotes before and after four weeks of treatment. The effects of ECEO on liver and kidney function in the tested mice were also evaluated. ECEO dose-dependently (p<0.001) inhibited the viability and the mean number of promastigotes and amastigote forms of L. tropica. Four weeks of treatment with ECEO at the doses of 2.5 and 5 mg/kg/ day significantly (p<0.001) improved the CL lesions and reduced the number of parasites in the infected mice. ECEO significantly increased NO production, apoptosis induction, and infection rate in parasites. The CC50 value for ECEO and MA was 303.4 µg/mL and 835.2 µg/mL, respectively. In the mice receiving ECEO at the doses of 2.5 and 5 mg/kg/day for 28 days, no significant change was reported between the serum level of liver enzymes and kidney factors when compared with the control group. ECEO displayed promising efficacy in parasite reduction in vitro and in the animal model. ECEO can thus be used as an alternative medicine to treat CL.

Hypertension and its risk factors among male adolescents in intermediate and secondary schools in Sakaka City, Aljouf Region of Saudi Arabia.

OBJECTIVE: Hypertension among adolescents is an emerging public health problem. The current study aims to estimate the burden of hypertension and identify its risk factors among male adolescents of intermediate and secondary schools. SUBJECTS AND METHODS: This is a school-based cross-sectional study that targeted 400 male adolescents in the age group of 15-17 years. Blood pressure was defined as per the "Fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents". An electronic device approved for use by the European Society of Hypertension International Protocol revision 2010, (Omron M3W; HEM-7202-E) was used for measuring blood pressure. CDC's body mass index tool was adopted for defining overweight and obesity. Descriptive analysis for hypertension and the risk factors were carried out. Chi-square test and odds ratios were calculated to assess any association between categorical variables. RESULTS: Overall 36 (9.0%) adolescents had prehypertension and 69 (17.2%) had hypertension. Systolic prehypertension, systolic hypertension, diastolic prehypertension, and diastolic hypertension were present in 6.5%, 17.2%, 5.8%, and 9.0% of the adolescents, respectively. Bivariate analysis revealed that overweight and obesity, no physical activity, or once-a-week physical activity, positive family history of hypertension, and smoking were predictors of systolic prehypertension and showed a significant relationship with systolic hypertension. CONCLUSION: There is a considerable prevalence of prehypertension and hypertension, among school-going male adolescents. We recommend school-based health education programs and routine screening directed toward the risk factors of noncommunicable diseases like hypertension with special attention to obesity, physical inactivity, and smoking.

Clean intermittent catheterization in Saudi children. Suggestion for a common protocol.

In the last thirty years, clean intermittent catheterization of urinary bladder has proven to be one of the most important advances in Urology. Clean intermittent catheterizationis already utilized in the Kingdom of Saudi Arabia, but the materials and the methods in use are not always the most appropriate. The acceptance of the long-term treatment with clean intermittent catheterization among Saudi families does not seem to be adequate. Moreover, the knowledge and the agreement about clean intermittent catheterization by Saudi Medical Community, and even among Urologists, does not seem to be satisfactory everywhere. We analyzed many different catheters and their cost. We prepared a list of suggestions about clean intermittent catheterization materials and methods. Following this protocol, the majority of the parents of our patients, properly informed and trained, do now understand very well the aims and the advantages of the method. Consequently we realized the problems are not necessarily coming from the patients and their families, but eventually from the inadequacy of our educational and supportive system. In this review, we present our common protocol for clean intermittent catheterization in children, hoping to avoid some mistakes and improve the quality of life of these patients. As cultural background, on the base of our own experience, we reanalyze the principles, indications, results, contraindications, and complications of clean intermittent catheterization in children.