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1.
PeerJ Comput Sci ; 10: e2086, 2024.
Article in English | MEDLINE | ID: mdl-38983219

ABSTRACT

User authentication is a fundamental aspect of information security, requiring robust measures against identity fraud and data breaches. In the domain of keystroke dynamics research, a significant challenge lies in the reliance on imposter datasets, particularly evident in real-world scenarios where obtaining authentic imposter data is exceedingly difficult. This article presents a novel approach to keystroke dynamics-based authentication, utilizing unsupervised outlier detection techniques, notably exemplified by the histogram-based outlier score (HBOS), eliminating the necessity for imposter samples. A comprehensive evaluation, comparing HBOS with 15 alternative outlier detection methods, highlights its superior performance. This departure from traditional dependence on imposter datasets signifies a substantial advancement in keystroke dynamics research. Key innovations include the introduction of an alternative outlier detection paradigm with HBOS, increased practical applicability by reducing reliance on extensive imposter data, resolution of real-world challenges in simulating fraudulent keystrokes, and addressing critical gaps in existing authentication methodologies. Rigorous testing on Carnegie Mellon University's (CMU) keystroke biometrics dataset validates the effectiveness of the proposed approach, yielding an impressive equal error rate (EER) of 5.97%, a notable area under the ROC curve of 97.79%, and a robust accuracy (ACC) of 89.23%. This article represents a significant advancement in keystroke dynamics-based authentication, offering a reliable and efficient solution characterized by substantial improvements in accuracy and practical applicability.

2.
Poult Sci ; 103(8): 103732, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38925079

ABSTRACT

The incidence of chronic respiratory disease (CRD) due to Mycoplasma gallisepticum (MG) contamination in hatching eggs poses a serious threat to poultry health and hatchability. Implementing effective sanitization methods while safeguarding the hatching potential of embryos is crucial. This study aimed to explore novel techniques for sanitizing hatching-fertile eggs to prevent and manage MG-associated CRD. The primary objective was to assess the efficacy of acidic electrochemically stimulated water (ECS), focusing on MG disinfection. Additionally, the study investigated 2 application methods, 1) electrostatic disinfection (ED) and 2) cold fog (CF) disinfection, to evaluate their bactericidal effects against MG-contaminated eggs. Deliberately infected MG strains were used for the experimental design, which compared the disinfection efficacy of ECS with its acidic properties. The comparison involved ED, which applies an electrostatic charge to water particles, and CF disinfection, a cold mist technique. Both methods aimed to target MG without compromising egg-hatching potential. The results indicated a significant (p < 0.05) reduction in colony-forming units per milliliter (CFU/mL). However, both application methods demonstrated distinct bactericidal effects. Eggs treated with electrostatic disinfection showed a significant (p < 0.001) reduction in embryonic mortality during incubation (10%) compared to control untreated eggs (18%). Similarly, the CF method exhibited a significant (p < 0.001) decrease in embryonic mortality (13%). The ECS potential in reducing embryonic mortality within the pH range of 2.5 to 6.5 was noted. Both the ED and CF methods show promise for preventing MG-induced hatchery infection while maintaining egg-hatching potential. This study presents innovative techniques to control MG in hatching eggs, contributing to improved poultry health and reduced CRD incidence.

3.
Sci Rep ; 14(1): 13004, 2024 06 06.
Article in English | MEDLINE | ID: mdl-38844514

ABSTRACT

Blast and gunshot-induced penetrating traumatic vascular injuries represent a significant portion of patients with vascular trauma in countries where there are higher rates of war-related violence. These injuries are especially challenging in resource-limited countries due to early diagnosis and transfer delays. This report aimed to present our experience regarding the surgical management and outcome of such injuries at a major referral vascular surgery centre in the country. A retrospective descriptive review of 326 patients with blast and gunshot-induced penetrating traumatic vascular injuries managed during a five-year period between April 2018 and April 2023. The demographics, mechanism of injury, type of vascular injury, Anatomical location, time to the operation, length of hospital stay, amount of blood products given, concomitant neuroskeletal injuries, development of Vascular injury associated acute kidney injury, surgical procedures performed and patient outcome were reviewed. In this study, 326 patients with 445 vascular injuries fulfilled the inclusion criteria. Most of the patients were male 92.3%, and the mean age was 28.3 ± 9.9 years. The gunshot mechanism of vascular injury was implicated in 76.1% of the injuries, and explosive-induced injury was 78 (23.9%). 193 (59.2%) of the patients had isolated arterial injuries, 117 (35.9%) patients had combined arterial and venous injuries while 18 (4.9%) patients had isolated venous injuries. The most commonly injured arteries were the femoral artery, followed by Brachial and popliteal artery injuries (26.1%, 23.5% and 19.4%, respectively). The median time to revascularization was 8.8 ± 8.7 h. 46.8% of the patients had Concomitant fractures, while 26.5% had Concomitant nerve injuries. Only three patients had temporary non-heparin-bound shunts during their arrival. The most common surgical intervention in arterial injuries was reversed saphenous vein graft 46.1%. The mortality was 5.8% and 7.7% of the patients needed secondary amputation. The majority of wartime arterial injuries are a result of Blast and gunshot vascular injuries. Frequent need for autologous vein grafts should be considered to manage such injuries. Results are encouraging despite delays in intervention; therefore, all viable limbs should be revascularized, keeping in mind the long-term functionality of the limb.


Subject(s)
Blast Injuries , Vascular System Injuries , Wounds, Gunshot , Humans , Male , Wounds, Gunshot/complications , Vascular System Injuries/surgery , Vascular System Injuries/etiology , Vascular System Injuries/diagnosis , Vascular System Injuries/epidemiology , Adult , Female , Retrospective Studies , Blast Injuries/surgery , Blast Injuries/epidemiology , Young Adult , Middle Aged , Adolescent , Vascular Surgical Procedures
4.
Arch Pharm (Weinheim) ; : e2400044, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38754070

ABSTRACT

New thiazole-clubbed piperazine derivatives were designed, synthesized, evaluated for their inhibitory capabilities against human acetylcholinesterase and butyrylcholinesterase (hAChE and/or hBuChE) and ß-amyloid (Aß) aggregation, and investigated for their metal chelating potential as multitarget agents for the treatment of Alzheimer's disease. Compounds 10, 19-21, and 24 showed the highest hAChE inhibitory activity at submicromolar concentrations, of which compound 10 was the most potent with a half-maximal inhibitory concentration (IC50) value of 0.151 µM. Compounds 10 and 20 showed the best hBuChE inhibitory activities (IC50 values of 0.135 and 0.103 µM, respectively), in addition to remarkable Aß1-42 aggregation inhibitory activities and metal chelating capabilities. Both compounds were further evaluated against human neuroblastoma SH-SY5Y and PC12 neuronal cells, where they proved noncytotoxic at their active concentrations against hAChE or hBuChE. They also offered a significant neuroprotective effect against Aß25-35-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Compound 10 displayed acceptable physicochemical properties and could pass the blood-brain barrier. The molecular docking study revealed the good binding interactions of compound 10 with the key amino acids of both the catalytic active site and the peripheral anionic site of hAChE, explaining its significant potency.

5.
Medicine (Baltimore) ; 103(10): e37356, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38457556

ABSTRACT

Plasma gelsolin (pGSN) correlates with clinical improvement in septic patients. We aimed to investigate pGSN levels as a diagnostic and prognostic marker of neonatal late-onset-sepsis (LOS). A case-control study was done on 184 neonates (92 with LOS and 92 controls). All participants were subjected to detailed history taking, full clinical evaluation, sepsis workup, and pGSN enzyme-linked immunosorbent-assay measurement. We detected significantly lower pGSN level among cases compared to controls (90.63 ±â€…20.64 vs 451.83 ±â€…209.59). It was significantly related to the severity of sepsis and mortality, with significantly lower values among cases with septic shock and multiorgan failure and non-survivors. Follow-up pGSN significantly increased after sepsis improvement in survivors compared to admission values. pGSN might be a reliable diagnostic and prognostic marker for LOS.


Subject(s)
Neonatal Sepsis , Sepsis , Infant, Newborn , Humans , Neonatal Sepsis/diagnosis , Gelsolin , Case-Control Studies , Sepsis/diagnosis , Hospitalization
6.
Int Breastfeed J ; 19(1): 9, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38303077

ABSTRACT

BACKGROUND: The World Health Organization recommends the use of donated human milk (HM) as the second-best option for mothers who are temporarily unable to provide sufficient breast milk to meet the needs of their infants. However, HM donation is yet to become an accepted practice in Uganda. We assessed the level of, and factors associated with acceptability to donate HM among postnatal mothers at St. Francis Hospital Nsambya (SFHN). METHODS: A cross-sectional sequential explanatory mixed method study was conducted between October 2018 and March 2019. A questionnaire on sociodemography, awareness and likely acceptability to donate HM was administered to 410 postnatal mothers at SFHN. Multivariate logistic regression analysis was undertaken to determine factors associated with acceptance of HM donation. Focus Group Discussions (4) and Key Informants Interviews (4) were used to explore factors influencing behaviours to donate human milk. Qualitative data were analysed using a content thematic approach. RESULTS: Overall acceptance of donating the HM was 77.6%, and the significant factors were: willingness to express the HM (AOR 7.5; 95% CI 3.01, 18.68); wet-nursing knowledge (AOR 2.3; 95% CI 1.1, 5.0) and visit to under-5 years' clinic (AOR 21.3; 95% CI 2.3, 196.9). The major themes in relation to accepting to donate HM were wet nursing experience, and confidence in donating the HM, and its perceived effectiveness. There were concerns about the safety and adequacy of HM and fear of transmitting criminal behaviours and mental illness through human milk. CONCLUSIONS: Acceptance to donate HM among postnatal mothers at St. Francis Hospital Nsambya was very high. Willingness to express and store human milk, prior knowledge about wet nursing and a visit to an under-five outpatient clinic were associated with acceptance. Thus, establishing a human milk bank is feasible in the study setting.


Subject(s)
Breast Feeding , Milk, Human , Female , Infant , Humans , Uganda , Cross-Sectional Studies , Health Knowledge, Attitudes, Practice , Hospitals
7.
Mol Genet Genomic Med ; 12(1): e2314, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37937857

ABSTRACT

BACKGROUND: Alström syndrome (AS) represents an exceptionally rare genetic disorder characterized by a constellation of features including cardiomyopathy, progressive hearing and vision impairment, as well as obesity. This study seeks to elucidate the genetic underpinnings of this syndrome within the Saudi Arabian population. METHODS: Employing an extended family cohort, we conducted an exhaustive molecular genetic assessment to delineate the presence of Alström syndrome. Additionally, we conducted an extensive review of existing literature from Saudi population to contextualize our findings within the broader understanding of the disorder in our country. RESULTS: Within our studied extended family, we identified two individuals harboring the homozygous pathogenic mutation (c.2729C>G) in the ALMS1 gene [NM_015120.4:c.2729C>G (p.Ser910*)]. Notably, carrier status was observed in the parents, whereas some siblings exhibited typical alleles while others were carriers of the mutation. Intriguingly, a review of the literature unveiled six distinct reports documenting a total of 20 Alström syndrome patients within the Saudi Arabian population, each presenting with distinct novel mutations. CONCLUSIONS: In cases featuring cardiomyopathy, obesity, and progressive hearing and vision loss, Alström syndrome merits inclusion within the differential diagnosis. To confirm the diagnosis, molecular genetic assessment of the ALMS1 gene is imperative, offering definitive clarity amidst the complex clinical presentation. This investigation reinforces the importance of genetic scrutiny for precise diagnosis and highlights the unique genetic landscape of Alström syndrome within the Saudi Arabian population.


Subject(s)
Alstrom Syndrome , Cardiomyopathies , Humans , Alstrom Syndrome/genetics , Alstrom Syndrome/diagnosis , Cell Cycle Proteins/genetics , Extended Family , Saudi Arabia , Obesity , Mutation
8.
Medicine (Baltimore) ; 102(51): e36713, 2023 Dec 22.
Article in English | MEDLINE | ID: mdl-38134055

ABSTRACT

Acute kidney damage (AKI) is a common cause of pediatric intensive care unit (PICU) admissions. Implementing a reno-protective strategy for AKI prediction can significantly enhance outcomes. The renal angina index (RAI) is a risk stratification tool used to predict severe AKI. We aim to assess the reliability and accuracy of the RAI scoring system in predicting AKI as compared to other conventional AKI markers. A prospective, observational study was conducted in the PICU of 2 tertiary medical centers in the Middle East. A total of 446 patients, aged 1-month to 14-years, without chronic kidney disease were enrolled. The RAI was calculated using the renal risk and renal injury score within the first 8 to 12 hours of admission. The accuracy of RAI was compared to changes in serum creatinine from baseline. The outcome was assessed on Day 3 for presence of AKI according to the kidney disease improving global outcome (KDIGO) criteria and associated sequelae. A positive RAI (RA+) was defined as RAI readings ≥ 8. Among the patients, 89 (19.9%) had a positive RAI within the first 8 to 12 hours of admission. The RA + group had a significantly higher occurrence of Day 3 severe AKI (KDIGO stages 2&3) compared to the RA- group (60.6% vs 4.2%, P < .001). The RA + group also had a significantly higher utilization of renal replacement therapy (RRT) (21.3% vs 1.1%, P < .001), longer mean PICU length of stay in days (11.1 ±â€…3.5 vs 5.5 ±â€…2.1, P < .001), and increased mortality (31.4% vs 2.8%, P < .001) compared to the RA- group. The RAI score demonstrated superior predictive ability for Day 3 AKI, with a sensitivity of 72%, specificity of 95%, and area under the curve (AUC) of 0.837, compared to changes in serum creatinine from baseline (sensitivity: 65%, specificity: 89%, AUC: 0.773), fluid overload (sensitivity: 43.7%, specificity: 79%, AUC: 0.613), and illness severity scores (sensitivity: 52.4%, specificity: 80.5%, AUC: 0.657). RAI proved to be a reliable and rapid bedside test for identifying critically ill children at risk of developing severe AKI. This enables physicians to implement reno-protective measures and intervene early, thereby improving prognosis.


Subject(s)
Acute Kidney Injury , Critical Illness , Child , Humans , Creatinine , Prospective Studies , Critical Illness/therapy , Reproducibility of Results , Acute Kidney Injury/diagnosis , Acute Kidney Injury/therapy , Acute Kidney Injury/epidemiology , Angina Pectoris/complications
9.
Medicine (Baltimore) ; 102(47): e36322, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-38013283

ABSTRACT

Vitamin D deficiency increases the risk of developing diabetes, dyslipidemia, and other chronic diseases. We aimed to investigate the relationship between vitamin D deficiency, glycemic levels, and lipid profiles in individuals with prediabetes and nondiabetes. This observational cross-sectional study was conducted on 249 adults who were divided into 2 groups based on the American Diabetes Association classification: nondiabetics and prediabetics. The serum vitamin D levels, lipid profiles, fasting blood glucose levels, hemoglobin A1c levels, fasting insulin levels, and insulin resistance (IR) were evaluated. The prevalence of vitamin D deficiency in all participants was 30.9%, and mean vitamin D levels were significantly [P = .0004] lower in prediabetics, who were more common in females. Furthermore, prediabetics had significantly higher serum triglycerides [P = .0006], and significantly lower serum high-density lipoprotein levels [P = .0148] than those nondiabetics. Serum cholesterol and low-density lipoprotein levels did not differ significantly between the 2 groups. 31.4% of all participants were overweight and 40.2% were obese. Furthermore, there was a strong correlation between vitamin D levels and IR and body mass indices ≥ 25 in prediabetics [r = -0.92] [P < .001]. Finally, vitamin D levels had a significant inverse relationship with glycemic parameters and IR, particularly in obese participants, but there was no significant relationship with lipid profile. In conclusion, vitamin D deficiency is common in females, regardless of whether they are prediabetics, but is more prevalent in prediabetics. Vitamin D deficiency is associated with high triglycerides and low high-density lipoprotein levels, but there were no significant changes in total cholesterol or low-density lipoprotein levels. Furthermore, vitamin D levels were negatively correlated with both fasting blood glucose and hemoglobin A1c levels, and its deficiency was strongly associated with IR especially in obese patients despite there being no significant correlation with blood lipids.


Subject(s)
Diabetes Mellitus , Insulin Resistance , Prediabetic State , Vitamin D Deficiency , Adult , Female , Humans , Glycated Hemoglobin , Blood Glucose , Saudi Arabia/epidemiology , Vitamin D Deficiency/complications , Vitamin D Deficiency/epidemiology , Vitamin D , Vitamins , Diabetes Mellitus/epidemiology , Obesity/complications , Obesity/epidemiology , Lipids , Triglycerides , Cholesterol , Lipoproteins, HDL , Lipoproteins, LDL
10.
Medicine (Baltimore) ; 102(47): e35906, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-38013323

ABSTRACT

Vertebral artery aneurysm is a rare condition with diverse clinical manifestations in pediatric patients. We present the case of a 12-year-old male who presented with diplopia, vomiting, ataxia, and severe headache. Diagnostic evaluation revealed an extracranial vertebral artery dissection with an associated aneurysm at the C3-C4 level. Despite the absence of recurrent ischemic strokes, the aneurysm posed challenges in differentiating the symptoms from other inflammatory demyelinating disorders, particularly internuclear ophthalmoplegia. Diagnosis relied on a thorough history, physical examination, and imaging studies. Magnetic resonance imaging with magnetic resonance angiography confirmed the diagnosis and played a crucial role in assessing the size, location, and extent of the aneurysm. Additionally, the imaging findings helped guide treatment decisions and determine the need for anticoagulation therapy. Regular follow-up imaging was initiated to monitor for late complications and evaluate the effectiveness of the management approach. This case highlights the atypical presentation of vertebral artery aneurysm in a pediatric patient, underscoring the importance of clinical suspicion and the role of advanced imaging techniques in facilitating accurate diagnosis and guiding appropriate management. Prompt diagnosis and optimal utilization of imaging modalities are essential in preventing severe morbidity and mortality. Further research is warranted to enhance our understanding of this condition and refine imaging and management protocols in pediatric population.


Subject(s)
Vertebral Artery Dissection , Male , Humans , Child , Vertebral Artery Dissection/diagnosis , Vertebral Artery Dissection/diagnostic imaging , Vertebral Artery/diagnostic imaging , Vertebral Artery/pathology , Magnetic Resonance Imaging , Magnetic Resonance Angiography
11.
Diagnostics (Basel) ; 13(15)2023 Jul 25.
Article in English | MEDLINE | ID: mdl-37568831

ABSTRACT

The most dangerous disease in recent decades is lung cancer. The most accurate method of cancer diagnosis, according to research, is through the use of histopathological images that are acquired by a biopsy. Deep learning techniques have achieved success in bioinformatics, particularly medical imaging. In this paper, we present an innovative method for rapidly identifying and classifying histopathology images of lung tissues by combining a newly proposed Convolutional Neural Networks (CNN) model with a few total parameters and the enhanced Light Gradient Boosting Model (LightGBM) classifier. After the images have been pre-processed in this study, the proposed CNN technique is provided for feature extraction. Then, the LightGBM model with multiple threads has been used for lung tissue classification. The simulation result, applied to the LC25000 dataset, demonstrated that the novel technique successfully classifies lung tissue with 99.6% accuracy and sensitivity. Furthermore, the proposed CNN model has achieved the lowest training parameters of only one million parameters, and it has also achieved the shortest processing time of just one second throughout the feature extraction process. When this result is compared with the most recent state-of-the-art approaches, the suggested approach has increased effectiveness in the areas of both disease classification accuracy and processing time.

12.
J Microsc Ultrastruct ; 11(2): 92-96, 2023.
Article in English | MEDLINE | ID: mdl-37448823

ABSTRACT

Background and Objectives: Salivary gland tumors (SGTs) are serious challenges to pathologists. Herein, we aimed to assess epidemiological and histopathological characteristics of SGTs among Sudanese patients. Materials and Methods: This retrospective descriptive study was undertaken at The pathology department in Khartoum State between 2008 and 2018. Patient records, histopathological reports, and slides were retrieved; and re-examined by two histopathologists. Diagnoses were reclassified according to the 2017 WHO classification of SGTs. Results: Overall, 150 cases of Sudanese patients with SGT were included (90 [60%] males and 60 [40%] females). Among these, 105 were benign (70%) and 45 were malignant (30%). The parotid glands were the most common site for both benign and malignant tumors (77/150; 51%: 59 benign (76.6%) and 18 malignant [23.4%]). The next common site was the submandibular gland (54 [36%]: 38 benign [70.3%] and 16 malignant [29.7%]), followed by minor salivary glands (19 [12.7%]: 8 benign and 11 malignant [57.9%]). Benign gland entities included pleomorphic adenoma (88/105; 83.7%), oncocytoma (5/105; 4.8%), myoepithelioma (4/105; 3.8%), Whartin tumors (3/105; 2.9%), basal cell adenoma (3/105; 2.9%), and sialolipoma (2/105; 1.9%). Malignant gland entities included adenoid cystic carcinoma (12; 26.7%), mucoepidermoid carcinoma (10; 22,2%), acinic cell carcinoma (6; 13.3%), poorly differentiated carcinoma (4; 8.9%), adenocarcinoma NOS (not otherwise specified) (4; 8.9%), basal cell adenocarcinoma (3; 6.7%), carcinoma ex pleomorphic adenoma (3; 6.7%), polymorphous adenocarcinoma (2; 4.4%), salivary duct carcinoma (1; 2.2%), and epithelial-myoepithelial carcinoma (2.2%). Conclusions: SGTs shared several epidemiological and histopathological features, exhibiting high incidence in the parotid and submandibular glands, lower prevalence in minor glands, and greater male predominance.

13.
IJID Reg ; 8: 31-35, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37415953

ABSTRACT

Objectives: Measles is a contagious disease associated with significant morbidity and mortality. This paper describes the clinical characteristics and outcomes of patients hospitalized with measles during an outbreak in Somalia from January 2018 to December 2021. Methods: This retrospective study was conducted at Mogadishu Somalia Turkey Recep Tayyip Erdogan Training and Research Hospital. Children aged 6 months to 17 years who were hospitalized with clinical signs and symptoms of measles and its complications were recruited. Results: In total, 110 participants were enrolled. The median age was 16 [interquartile range (IQR) 12-36] years, and 87 (79.1%) were male. All participants presented with fever, typical measles rash, cough and conjunctivitis, and 43 (39.1%) had received the measles vaccine. Overall, 104 (94.6%) participants were admitted with severe respiratory symptoms, and six (5.4%) were admitted due to poor feeding and/or significant dehydration. Overall, all-cause mortality was 1.8% (n=2). The median duration of hospitalization was longer among participants who died compared with those who survived [11 (IQR 8-14) vs 4 (IQR 2-6) days; P=0.046]. Unvaccinated participants were significantly younger than vaccinated participants [36 (IQR 24-72) vs 12 (IQR 9-16) months; P<0.001]. There was a trend towards higher mortality [0/43 (0%) vs 2/67 (3%); P=0.519] and longer length of hospitalization [3 (IQR 2-6) vs 4 (IQR 3-7) days; P=0.056] among unvaccinated participants compared with vaccinated participants. Both the median total leukocyte count [5.7 (IQR 3.9-8.5) vs 11.6 (IQR 5.9-46.3) x 109/L; P<0.001] and platelet count [239 (IQR 202-358) vs 308 (IQR 239-404) x 109/L; P=0.032] were significantly higher among unvaccinated participants compared with vaccinated participants. However, the median haemoglobin concentration was significantly higher among vaccinated participants compared with unvaccinated participants [11.1 (IQR 9.9-12.3) vs 10.1 (IQR 9.1-11.2) g/dL; P=0.006]. Conclusions: Patients with measles in Somalia have a short hospital stay, low mortality rate and low vaccination rate. Timely vaccination and the need for improved care of patients with measles, particularly vulnerable groups including children and those with undernutrition, are encouraged.

14.
ACS Omega ; 8(29): 26012-26034, 2023 Jul 25.
Article in English | MEDLINE | ID: mdl-37521639

ABSTRACT

To develop multitarget-directed ligands (MTDLs) as potential treatments for Alzheimer's disease (AD) and to shed light on the effect of the chromene group in designing these ligands, 35 new tacrine-chromene derivatives were designed, synthesized, and biologically evaluated. Compounds 5c and 5d exhibited the most desirable multiple functions for AD; they were strong hAChE inhibitors with IC50 values of 0.44 and 0.25 µM, respectively. Besides, their potent BuChE inhibitory activity was 10- and 5-fold more active than rivastigmine with IC50 = 0.08 and 0.14 µM, respectively. Moreover, they could bind to the peripheral anionic site (PAS), influencing Aß aggregation and decreasing Aß-related neurodegeneration, especially compound 5d, which was 8 times more effective than curcumin with IC50 = 0.74 µM and 76% inhibition at 10 µM. Compounds 5c and 5d showed strong BACE-1 inhibition at the submicromolar level with IC50 = 0.38 and 0.44 µM, respectively, which almost doubled the activity of curcumin. They also showed single-digit micromolar inhibitory activity against MAO-B with IC50 = 5.15 and 2.42 µM, respectively. They also had antioxidant activities and showed satisfactory metal-chelating properties toward Fe+2, Zn+2, and Cu+2, inhibiting oxidative stress in AD brains. Furthermore, compounds 5c and 5d showed acceptable relative safety upon normal cells SH-SY5Y and HepG2. It was shown that 5c and 5d were blood-brain barrier (BBB) penetrants by online prediction. Taken together, these multifunctional properties highlight that compounds 5c and 5d can serve as promising candidates for the further development of multifunctional drugs against AD.

15.
Glob Heart ; 18(1): 37, 2023.
Article in English | MEDLINE | ID: mdl-37361321

ABSTRACT

Background: Valve replacement surgery (VRS) improves clinical outcomes in patients with severe rheumatic heart disease (RHD). However, lifelong anticoagulation and frequent monitoring are required, which potentially impacts health-related quality of life (HRQoL). In this study, we assessed the HRQoL of people with RHD in Uganda following VRS. Methods: This was a hospital-based, cross-sectional study conducted between March and August 2021. Eligible participants were individuals who had VRS before the age of 18 years. The Pediatric Quality of Life Inventory-Cardiac Module (PedsQL-Cardiac module) was used to evaluate HRQoL. A total mean score of ≥ 80% was considered as optimal HRQoL. Results: Of the 83 eligible participants, 52 (60.5%) were female, with a median age of 18 (interquartile range: 14-22) years. Most participants had NYHA I functional status (n = 79, 92%). Most (n = 73, 92.4%) surgeries were performed outside of Uganda, and 61 (72.6%) were single mechanical valve replacement. Almost half (n = 45, 54%) expressed no concern about being on life-long warfarin therapy. However, 24 (29.3%) feared bleeding. The optimal mean score of cardiac-specific HRQoL was achieved in 50 (60.2%) of participants. Factors associated with optimal HRQoL were body mass index (BMI) (adjusted odds ratio (aOR), 1.2, 95% Confidence Interval: 1.1-1.3, p = 0.006), being afraid of bleeding or bruising (aOR: 1.5, 95% CI: 1.21-2.47, p = 0.004), acceptance of having an artificial valve (aOR: 2.7, 95% CI; 1.64-3.81, p < 0.001). Conclusion: HRQoL was optimal in about three in five participants following VRS. Increasing BMI and acceptance of artificial valve were significantly associated with optimal HRQoL.


Subject(s)
Quality of Life , Rheumatic Heart Disease , Humans , Child , Female , Adolescent , Young Adult , Adult , Male , Rheumatic Heart Disease/epidemiology , Rheumatic Heart Disease/surgery , Uganda/epidemiology , Cross-Sectional Studies , Anticoagulants/therapeutic use
16.
Biomedicines ; 11(4)2023 Mar 29.
Article in English | MEDLINE | ID: mdl-37189672

ABSTRACT

A safe and effective treatment for liver cancer is still elusive despite all attempts. Biomolecules produced from natural products and their derivatives are potential sources of new anticancer medications. This study aimed to investigate the anticancer potential of a Streptomyces sp. bacterial extract against diethylnitrosamine (DEN)-induced liver cancer in Swiss albino mice and explore the underlying cellular and molecular mechanisms. The ethyl acetate extract of a Streptomyces sp. was screened for its potential anticancer activities against HepG-2 using the MTT assay, and the IC50 was also determined. Gas chromatography-mass spectrometric analysis was used to identify the chemical constituents of the Streptomyces extract. Mice were administered DEN at the age of 2 weeks, and from week 32 until week 36 (4 weeks), they received two doses of Streptomyces extract (25 and 50 mg/kg body weight) orally daily. The Streptomyces extract contains 29 different compounds, according to the GC-MS analysis. The rate of HepG-2 growth was dramatically reduced by the Streptomyces extract. In the mice model. Streptomyces extract considerably lessened the negative effects of DEN on liver functions at both doses. Alpha-fetoprotein (AFP) levels were significantly (p < 0.001) decreased, and P53 mRNA expression was increased, both of which were signs that Streptomyces extract was suppressing carcinogenesis. This anticancer effect was also supported by histological analysis. Streptomyces extract therapy additionally stopped DEN-induced alterations in hepatic oxidative stress and enhanced antioxidant activity. Additionally, Streptomyces extract reduced DEN-induced inflammation, as shown by the decline in interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) levels. Additionally, the Streptomyces extract administration dramatically boosted Bax and caspase-3 levels while decreasing Bcl-2 expressions in the liver according to the Immunohistochemistry examination. In summary, Streptomyces extract is reported here as a potent chemopreventive agent against hepatocellular carcinoma through multiple mechanisms, including inhibiting oxidative stress, cell apoptosis, and inflammation.

17.
Eur Rev Med Pharmacol Sci ; 27(6): 2646-2658, 2023 03.
Article in English | MEDLINE | ID: mdl-37013783

ABSTRACT

OBJECTIVE: Gefitinib (GFB) was loaded into different designs of thermos- and pH-responsive polymer-based hydrogels, namely chitosan (CH) and Pluronic F127 (Pl F127) with the aid of a crosslinking ß-glycerophosphate (ß-GP). MATERIALS AND METHODS: GFB was loaded in CH and P1 F127 hydrogel. The preparation was characterized and tested for their stability and efficacy as antitumor injectable therapy devices. The antiproliferative effect of the selected CH/ß-GP hydrogel formula was investigated against the hepatic cancerous cell, HepG2 using the MTT tetrazolium salt colorimetric assay. Furthermore, the pharmacokinetic was performed for GEF using a developed, reported and validated LC method. RESULTS: All hydrogel samples showed no changes in color, separation(s), and crystallization in both liquid and gel forms. The CH/ß-GP system showed a lower viscosity (110.3 ± 5.2 Cp) compared to CH/ß-GP/Pl F127 system (148.4 ± 4.4 Cp) in the sol phase. Also, the results confirmed a continued increase in rats' plasma during the first four days (Tmax) with a plasma peak level (Cmax) of 3.663 µg/mL followed by a decrease below the detection limit after 15 days. Moreover, the results indicated no significant difference (p < 0.05) between the predicted and observed GEF-concentration data and that the proposed CH-based hydrogel facilitated its sustained release as distinguished from the longer value of MRT of 9 days and an AUC0-t of 41.917 µg/L/day. CONCLUSIONS: The medicated CH/ß-GP hydrogel formula had a higher targeting-controlled efficiency against a solid tumor than the free poor water soluble GFB.


Subject(s)
Antineoplastic Agents , Chitosan , Neoplasms , Rats , Animals , Hydrogels , Gefitinib , Polymers , Antineoplastic Agents/pharmacology , Poloxamer , Temperature
18.
Materials (Basel) ; 16(4)2023 Feb 13.
Article in English | MEDLINE | ID: mdl-36837180

ABSTRACT

Recycled construction cementitious materials (RCCM) and red mud (RM) could be considered a type of discarded material with potential cementitious properties. Generally, landfilling and stacking are utilized to dispose of this type of solid waste, which can be detrimental to the environment and sustainability of the construction sector. Accordingly, a productive process for making eco-efficient alkali-activated slag-based samples with the inclusion of RCCM and red mud is studied in this paper. Dehydrated cement powder (DCP) is attained through the high-temperature treatment of RCCM, and red mud can be obtained from the alumina industry. Subsequently, DCP and RM are utilized as a partial substitute for granulated blast furnace slag (GBFS) in alkali-activated mixtures. Two different batches were designed; the first batch had only DCP at a dosage of 15%, 30%, 45%, and 60% as a partial substitute for GBFS, and the second batch had both DCP and RM at 15%, 30%, 45%, and 60% as a partial substitute for GBFS. Different strength and durability characteristics were assessed. The findings show that when both dehydrated cement powder and red mud are utilized in high quantities, the strength and durability of the specimens were enhanced, with compressive strength improving by 42.2% at 28 days. Such improvement was obtained when 7.5% each of DCP and RM were added. The results revealed that DCP and RM have a negative effect on workability, whilst they had a positive impact on the drying shrinkage as well as the mechanical strength. X-ray diffraction and micro-structural analysis showed that when the amount of DCP and RM is increased, a smaller number of reactive products forms, and the microstructure was denser than in the case of the samples made with DCP alone. It was also confirmed that when DCP and RM are used at optimized dosages, they can be a potential sustainable binder substitute; thus, valorizing wastes and inhibiting their negative environmental footprint.

19.
Animal ; 17(1): 100696, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36587589

ABSTRACT

Some studies have suggested that dietary medicinal plants or herbs may have a variety of biological functions such as anti-inflammatory, antiallergic, antifungal, antioxidative stress, and anticarcinogenic activities. The present study was undertaken to assess the incorporation of the extract of licorice supplementation on the growth performance, carcass yield, blood indices, and antioxidative capacity in broilers. Three hundred twenty unsexed one-day-old Ross 308 broiler chicks were allocated randomly into four groups. Chicks in each group were randomly subdivided into eight replicates of ten chicks. The first group received a basal diet and was considered a control. The respective groups received a basal diet supplemented with 1, 2, and 3 g licorice extract/kg diet. The obtained results indicated that supplementation of licorice extract to broiler chicks resulted in heavier BW and weight gain and a better feed conversion ratio during the experimental periods compared with the control group. However, feed consumption increased during the entire growing period. Supplementing the broiler's diet with licorice extract led to a higher value of erythrocytes, leukocytes, haemoglobin, plasma total protein, albumin, and antioxidant concentration and a low value in plasma cholesterol, triglycerides, uric acid, urea, and total cholesterol. It could be concluded that the dietary addition of licorice extracts 2 and 3 g licorice extract/kg diet improved broiler chicks' growth performance and physiological status.


Subject(s)
Antioxidants , Glycyrrhiza , Animals , Antioxidants/pharmacology , Antioxidants/metabolism , Chickens , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Dietary Supplements , Diet/veterinary , Glycyrrhiza/metabolism , Cholesterol/metabolism
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