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1.
Cureus ; 16(4): e58244, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38745788

RESUMEN

Objective The objective of this study was to assess the prevalence of hypomagnesemia and its association with the severity of acute ischemic stroke (AIS) in patients presenting at a tertiary care hospital. Methodology A total of 100 patients with AIS were included in the study. Demographic data, including age, gender, and severity of stroke, were collected. Serum magnesium levels were measured at admission, and the severity of stroke was classified as mild, moderate, or severe based on clinical criteria. The presence of hypomagnesemia was defined as a serum magnesium level below 1.8 mg/dL determined within 72 hours of onset of stroke. Statistical analysis was performed to assess the association between hypomagnesemia, stroke severity, age, and gender. Results The mean age of the patients with standard deviation was 65.45 ± 11.8 years, with the majority (38, 38%) aged 60-74 years. There were 53 (53%) male and 47 (47%) female patients. Hypomagnesemia was found in 35 (35%) patients, with an average magnesium level of 1.93 mg/dL and a standard deviation of 0.37 at admission. There was no statistically significant difference in the distribution of stroke severity (P = 0.779; P = 0.406) or hypomagnesemia (P = 0.287; P = 0.591) based on gender or age group, respectively. Stratification based on stroke severity showed that 16 (39%) patients with mild stroke, 10 (31.3%) with moderate stroke, and 9 (33.3%) with severe stroke had hypomagnesemia. The correlation between stroke severity and hypomagnesemia was weak (r = 0.099). Further, among hypomagnesemia patients, the majority were females aged 60-74 years. Conclusions This study found a weak positive relationship between the severity of AIS and the presence of hypomagnesemia. However, no statistically significant association was observed between gender or age group and stroke severity or hypomagnesemia. These findings suggest that further research is needed to understand the role of hypomagnesemia in AIS and its potential implications for patient management.

2.
Ann Med Surg (Lond) ; 86(5): 2562-2571, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38694302

RESUMEN

Background: Increased COVID-19 transmission among the populace may be caused by healthcare workers (HCWs) who lack knowledge, awareness, and good preventive practices. Additionally, it may cause elevated stress levels, anxiety, poor medical judgement, and situational overestimation. Objectives: The present survey aimed to assess knowledge and risk perception regarding COVID-19 among HCWs in Khyber Pakhtunkhwa (KP), Pakistan. Methodology: A web-based online, pre-tested questionnaire comprising 26 items was circulated via social media in April 2020 amongst HCWs in major tertiary care facilities in KP. Results: The study's results, revealing both the commendable knowledge levels among HCWs about COVID-19 and their heightened risk perception, highlight the critical need for targeted interventions to address the potential impact on self-protective behaviour and mental health within this vital workforce. This insight is important for designing strategies that not only enhance HCWs' well-being but also ensure the continued effectiveness of healthcare delivery during pandemics. The percentage mean score (PMS) of COVID-19 knowledge was 85.14±10.82. Male HCWs and those with an age older than or equal to 32 years demonstrated a higher knowledge score (85.62±11.08; P=0.032 and 87.59±7.33, P=0.021, respectively). About 76% of HCWs feared contracting COVID-19. Nearly 82% of respondents were mentally preoccupied with the pandemic and also terrified of it. 'Of these, 81% were nurses, 87% had a job experience of 6-8 years and 54.45% were frontline workers. Feelings of panic and concern about the pandemic were found to be more in HCWs who were physicians above the age of 32, and who had 3-5 years of work experience. HCWs' overall risk perception was found to be significantly different between males (7.04±2.26) and females (8.01±1.97), job experience of 6-10 years (8.04±177) with 3-5 years and younger than or equal to 2 years job experience (7.18±2.43,6.93±2.22), respectively, and between frontline HCWs (7.50±2.10) and non-frontline HCWs (6.84±2.40). Conclusion: HCWs demonstrated good knowledge about COVID-19. As the risk perception of COVID-19 among HCWs is high, it can raise concerns about their self-protective behaviour, and mental health. These issues need to be addressed.

4.
Front Bioeng Biotechnol ; 12: 1364700, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38694624

RESUMEN

Dopamine is one of the most important neurotransmitters and plays a crucial role in various neurological, renal, and cardiovascular systems. However, the abnormal levels of dopamine mainly point to Parkinson's, Alzheimer's, cardiovascular diseases, etc. Hydroxyapatite (HAp), owing to its catalytic nature, nanoporous structure, easy synthesis, and biocompatibility, is a promising matrix material. These characteristics make HAp a material of choice for doping metals such as cobalt. The synthesized cobalt-doped hydroxyapatite (Co-HAp) was used as a colorimetric sensing platform for dopamine. The successful synthesis of the platform was confirmed by characterization with FTIR, SEM, EDX, XRD, TGA, etc. The platform demonstrated intrinsic peroxidase-like activity in the presence of H2O2, resulting in the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). The proposed sensor detected dopamine in a linear range of 0.9-35 µM, a limit of detection of 0.51 µM, limit of quantification of 1.7 µM, and an R2 of 0.993. The optimization of the proposed sensor was done with different parameters, such as the amount of mimic enzyme, H2O2, pH, TMB concentration, and time. The proposed sensor showed the best response at 5 mg of the mimic enzyme, pH 5, 12 mM TMB, and 8 mM H2O2, with a short response time of only 2 min. The fabricated platform was successfully applied to detect dopamine in physiological solutions.

5.
Clin Case Rep ; 12(5): e8875, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38736569

RESUMEN

The presented primary thyroid leiomyosarcoma (TL) case report underscores the importance of recognizing and addressing the diagnostic challenges and management complexities associated with this exceedingly rare malignancy. Given the limited effective therapeutic strategies available, timely intervention, thorough diagnostics, and vigilant follow-up are paramount in managing such intricate tumors. Further research focusing on molecular-based treatment modalities is imperative to improve patient outcomes in cases of primary TL.

6.
Proc Natl Acad Sci U S A ; 121(17): e2320713121, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38621119

RESUMEN

As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-CoV-2 main protease (Mpro) DAA, has been significant for treatment of patients. A limitation of this DAA, however, is that the antiviral component, nirmatrelvir, is rapidly metabolized and requires inclusion of a CYP450 3A4 metabolic inhibitor, ritonavir, to boost levels of the active drug. Serious drug-drug interactions can occur with Paxlovid for patients who are also taking other medications metabolized by CYP4503A4, particularly transplant or otherwise immunocompromised patients who are most at risk for SARS-CoV-2 infection and the development of severe symptoms. Developing an alternative antiviral with improved pharmacological properties is critical for treatment of these patients. By using a computational and structure-guided approach, we were able to optimize a 100 to 250 µM screening hit to a potent nanomolar inhibitor and lead compound, Mpro61. In this study, we further evaluate Mpro61 as a lead compound, starting with examination of its mode of binding to SARS-CoV-2 Mpro. In vitro pharmacological profiling established a lack of off-target effects, particularly CYP450 3A4 inhibition, as well as potential for synergy with the currently approved alternate antiviral, molnupiravir. Development and subsequent testing of a capsule formulation for oral dosing of Mpro61 in B6-K18-hACE2 mice demonstrated favorable pharmacological properties, efficacy, and synergy with molnupiravir, and complete recovery from subsequent challenge by SARS-CoV-2, establishing Mpro61 as a promising potential preclinical candidate.


Asunto(s)
Antivirales , Citidina/análogos & derivados , Hepatitis C Crónica , Hidroxilaminas , Lactamas , Leucina , Nitrilos , Prolina , Ritonavir , Humanos , Animales , Ratones , Antivirales/farmacología , Protocolos Clínicos , Combinación de Medicamentos
7.
Plant Signal Behav ; 19(1): 2336724, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38600704

RESUMEN

Biostimulants are obtained from various sources like plants, animals, microorganisms, and industrial by-products as well as waste material. Their utilization in agriculture practices is being increased that is giving positive results. The purpose of the current study was to use plant-derived smoke (SMK) solution and biogas digestate (BGD) slurry as biostimulant to elucidate their impact on potato (Solanum tuberosum) performance. The experiment was conducted in lab as well as field conditions, and SMK and BGD solutions were prepared in varying concentrations such as SMK 1:500, SMK 1:250, BGD 50:50, and BGD 75:25. Foliar applications were performed thrice during experiments and data were collected related to photosynthesis, growth, pigments, and genome-wide methylation profiling. Net photosynthesis rate (A) and water use efficiency (WUE) were found higher in SMK- and BGD-treated lab and field grown plants. Among pigments, BGD-treated plants depicted higher levels of Chl a and Chl b while SMK-treated plants showed higher carotenoid levels. Alongside, enhancement in growth-related parameters like leaf number and dry weight was also observed in both lab- and field-treated plants. Furthermore, DNA methylation profile of SMK- and BGD-treated plants depicted variation compared to control. DNA methylation events increased in all the treatments compared to control except for SMK 1:500. These results indicate that smoke and slurry both act as efficient biostimulants which result in better performance of plants. Biostimulants also affected the genome-wide DNA methylation profile that resultantly might have changed the plant gene expression profiling and played its role in plant responsiveness to these biostimulants. However, there is need to elucidate a possible synergistic effect of SMK and BGD on plant growth along with gene expression profiling.


Asunto(s)
Humo , Solanum tuberosum , Animales , Solanum tuberosum/metabolismo , Biocombustibles , Fotosíntesis , Metilación
8.
Ann Med Surg (Lond) ; 86(4): 1933-1941, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38576948

RESUMEN

Background and aims: Increased use of digital devices in the modern era has led to the development of digital eye strain (DES) or computer vision syndrome in their users. This can result in the development of various ocular and visual symptoms among them. In this study, the authors aimed to view the prevalence of digital eye strain among radiology physicians in Pakistan and their associated risk factors. Materials and methods: A cross-sectional study was conducted to evaluate occupational DES among radiology physicians in Pakistan. The data collection was done using the convenience sampling technique, and the data were analyzed using IBM SPSS for Windows, Version 25.0. Results: Out of the 247 respondents, 33.6% were males and 66.4% were females. 41.7% of them were between 30 and 40 years of age and 51.8% of them were radiology residents. 52.2% of the participants had a refractive error and were using a corrective lens. The majority of the radiologists in our study (84.2%) preferred picture archiving and communication system (PACS) over films and 82.2% of them reported having breaks of less than 15 min. Major symptoms reported by the participants were tired or heavy eyes (69.6%) and headache (69.3%). The proportion of developing DES was higher in females [P=0.001, adjusted odds ratio (aOR)=2.94], radiology residents (P=0.031, aOR=3.29), and working hours of more than 4 h per day (P<0.001, aOR=0.04). Conclusion: With recent advances in the field of radiology in Pakistan, the frequency of developing DES among radiologists is increasing. Being a female, having long working hours, and having noticeable flickers on the digital screens were among the significant factors in developing DES among radiologists.

9.
ACS Omega ; 9(13): 15271-15281, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38585130

RESUMEN

Germin and Germin-like proteins (GLPs) are a class of plant proteins that are part of the Cupins superfamily, found in several plant organs including roots, seeds, leaves, and nectar glands. They play a crucial role in plant defense against pathogens and environmental stresses. Herein, this study focused on the promoter analysis of OsGLP12-3 in rice cultivar Swat-1 to elucidate its regulation and functions. The region (1863bp) of the OsGLP12-3 promoter from Swat-1 genomic DNA was amplified, purified, quantified, and cloned using Topo cloning technology, followed by sequencing. Further in silico comparative analysis was conducted between the OsGLP12-3 promoters from Nipponbare and Swat-1 using the Plant CARE database, identifying 24 cis-acting regulatory elements with diverse functions. These elements exhibited distinct distribution patterns in the 2 rice varieties. The OsGLP12-3 promoter revealed an abundance of regulatory elements associated with biotic and abiotic stress responses. Computational tools were employed to analyze the regulatory features of this region. In silico expression analysis of OsGLP12-3, considering various developmental stages, stress conditions, hormones, and expression timing, was performed using the TENOR tool. Pairwise alignment indicated 86% sequence similarity between Nipponbare and Swat-1. Phylogenetic analysis was conducted to explore the evolutionary relationship between the OsGLP12-3 and other plant GLPs. Additionally, 2 unique regulatory elements were modeled and docked, GARE and MBS to understand their hydrogen bonding interactions in gene regulation. The study highlights the importance of OsGLP12-3 in plant defense against biotic and abiotic stresses, supported by its expression patterns in response to various stressors and the presence of specific regulatory elements within its promoter region.

11.
Int J Biol Macromol ; 269(Pt 1): 131869, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38670195

RESUMEN

Protein glycation in human body is closely linked to the onset/progression of diabetes associated complications. These glycated proteins are commonly known as advanced glycation end products (AGEs). Recent literature has also highlighted the involvement of AGEs in other non-communicable diseases (NCDs) such as cardiovascular, cancer, and Alzheimer's diseases and explored the impact of plant metabolites on AGEs formation. However, the significance of endophytic metabolites against AGEs has recently garnered attention but has not been thoroughly summarized thus far. Therefore, the objective of this review is to provide a comprehensive overview of the importance of endophytic metabolites in combating AGEs under NCDs conditions. Additionally, this review aims to elucidate the processes of AGEs formation, absorption, metabolism, and their harmful effects. Collectively, endophytic metabolites play a crucial role in modulating signaling pathways and enhancing the digestibility properties of gut microbiota (GM) by targeting on AGEs/RAGE (receptor for AGEs) axis. Furthermore, these metabolites exhibit anti-AGEs activities similar to those derived from host plants, but at a lower cost and higher production rate. The use of endophytes as a source of such metabolites offers a risk-free and sustainable approach that holds substantial potential for the treatment and management of NCDs.

12.
Asian J Psychiatr ; 95: 104005, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38513509

RESUMEN

INTRODUCTION: Cariprazine is an orally active dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, being considered as a treatment for refractory MDD. Therefore, we aim to perform the first meta-analysis of current literature, to collate changes in depression from baseline and assess tolerability of adjunctive cariprazine in MDD populace. METHODS: PubMed, Embase, Google Scholar, ClinicalTrials.Gov, and Cochrane Library were searched from inception till 1st September 2023. RCTs of adult patients with refractory MDD under adjunctive cariprazine vs. placebo were included. Primary outcomes included improvement in MADRS, CGI-S, and HAM-D 17 scores. Secondary outcomes included treatment-emergent adverse events. The statistical analysis was performed using generic inverse variance with random-effects model. The overall risk ratios (RR) were calculated for dichotomous outcomes. RESULTS: A total of five RCTs were analysed, enrolling 2013 participants (cariprazine: 959 participants, Placebo: 1054). Supplementation of ADT with cariprazine demonstrated a significant improvement in MADRAS, CGI-S and HAMD-17 scores from baseline (LSMD: -1.88, 95% CI [-2.94, -0.83], p=0.0005), (LSMD: -0.18, 95% CI [-0.29, -0.07], p=0.002), and (LSMD: -0.96, 95% CI [-1.70, -0.21], p=0.01) respectively. Treatment with adjunctive cariprazine therapy demonstrated significantly increased incidence of akathisia, nausea, dizziness, fatigue, restlessness, somnolence, and tremors when compared with placebo. CONCLUSION: Our meta-analysis provides evidence supporting the efficacy of adjunctive cariprazine in patients with refractory MDD. However, it is essential to consider the safety profile of cariprazine, particularly the increased risk of adverse events. The vigilant monitoring and management of these side effects should be integrated into clinical practice to minimize discontinuation rates and optimize patient outcomes.


Asunto(s)
Trastorno Depresivo Mayor , Trastorno Depresivo Resistente al Tratamiento , Piperazinas , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Piperazinas/farmacología , Quimioterapia Combinada , Antidepresivos/administración & dosificación , Antidepresivos/efectos adversos , Evaluación de Resultado en la Atención de Salud
13.
Cells ; 13(6)2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38534392

RESUMEN

Age-related macular degeneration (AMD), characterized by macular retinal degeneration, poses a significant health concern due to the lack of effective treatments for prevalent dry AMD. The progression of AMD is closely linked to reactive oxygen species and Fas signaling, emphasizing the need for targeted interventions. In this study, we utilized a NaIO3-induced retinal degeneration mouse model to assess the efficacy of Fas-blocking peptide (FBP). Intravitreal administration of FBP successfully suppressed Fas-mediated inflammation and apoptosis, effectively arresting AMD progression in mice. We developed a 6R-conjugated FBP (6R-FBP) for eye drop administration. 6R-FBP, administered as an eye drop, reached the retinal region, attenuating degeneration by modulating the expression of inflammatory cytokines and blocking Fas-mediated apoptosis in rodent and rabbit NaIO3-induced retinal degeneration models to address practical concerns. Intravitreal FBP and 6R-FBP eye drops effectively reduced retinal degeneration and improved retinal thickness in rodent and rabbit models. This study highlights the therapeutic potential of FBP, particularly 6R-FBP as an eye drop, in inhibiting Fas-mediated cell signaling and protecting against retinal cell death and inflammation in dry AMD. Future investigations should explore the translational prospects of this approach in primates with eye structures comparable to those of humans.


Asunto(s)
Degeneración Macular , Degeneración Retiniana , Humanos , Ratones , Animales , Conejos , Soluciones Oftálmicas/uso terapéutico , Degeneración Macular/metabolismo , Péptidos/uso terapéutico , Inflamación
14.
Angew Chem Int Ed Engl ; 63(19): e202400110, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38484279

RESUMEN

The electrolyte concentration not only impacts the battery performance but also affects the battery cost and manufacturing. Currently, most studies focus on high-concentration (>3 M) or localized high-concentration electrolytes (~1 M); however, the expensive lithium salt imposes a major concern. Most recently, ultralow concentration electrolytes (<0.3 M) have emerged as intriguing alternatives for battery applications, which feature low cost, low viscosity, and extreme-temperature operation. However, at such an early development stage, many works are urgently needed to further understand the electrolyte properties. Herein, we introduce an ultralow concentration electrolyte of 2 wt % (0.16 M) lithium difluoro(oxalato)borate (LiDFOB) in standard carbonate solvents. This electrolyte exhibits a record-low salt/solvent mass ratio reported to date, thus pointing to a superior low cost. Furthermore, this electrolyte is highly compatible with commercial Li-ion materials, forming stable and inorganic-rich interphases on the lithium cobalt oxide (LiCoO2) cathode and graphite anode. Consequently, the LiCoO2-graphite full cell demonstrates excellent cycling performance. Besides, this electrolyte is moisture-resistant and effectively suppresses the generation of hydrogen fluoride, which will markedly facilitate the battery assembly and recycling process under ambient conditions.

15.
Open Med (Wars) ; 19(1): 20240897, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38463529

RESUMEN

Cardiovascular diseases are the leading cause of mortality and morbidity globally. Clinicians must know cutaneous signs of cardiovascular disease, including petechiae, macules, purpura, lentigines, and rashes. Although cutaneous manifestations of diseases like infectious endocarditis and acute rheumatic fever are well established, there is an indispensable need to evaluate other important cardiovascular diseases accompanied by cutaneous signs. Moreover, discussing the latest management strategies in this regard is equally imperative. This review discusses distinctive skin findings that help narrow the diagnosis of cardiovascular diseases and recommendations on appropriate treatment.

16.
Int J Dev Disabil ; 70(2): 173-183, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38481463

RESUMEN

Objective: This review summarizes evidence pertaining to the impact of the COVID-19 pandemic on the psychological health of children and adolescents with autism spectrum disorder (ASD). Materials and Methods: An electronic search was conducted using four major databases: PubMed, ScienceDirect, Web of Science, and Google Scholar. Using an umbrella methodology, the reference lists of relevant papers were reviewed, and citation searches were conducted. The study included articles written in English between January 2020 and March 2021 that focused on the psychological health of autistic children and adolescents. Results: All eight studies included in the final review were cross-sectional. Three of the eight studies were conducted in Italy, two in Turkey, and one study each in Portugal, Spain, and the United Kingdom, with a total of 1,407 participants. All studies used a mixture of standardized and non-standardized questionnaires to collect data. The total number of patients were 1407 at a mean age of 9.53 (SD = 2.96) years. Seven studies report gender; male 74.7% (657/880) and female 25.3% (223/880). The finding showed that behavioral issues in children and adolescents with ASD have significantly increased; 521 (51.9 percent) of the 1004 individuals with ASD presented with behavioral changes, including conduct problems, emotional problems, aggression, and hyperactivity. Some studies also found increased anxiety and difficulties managing emotions. Only one study reported clinical stabilization in children with ASD during COVID-19. Finally, 82.7% of families and caregivers of children with ASD (544 out of 658) faced challenges during COVID-19. Conclusion: Although the studies in this review suggest a general worsening of ASD children's clinical status, it remains difficult to draw definitive conclusions at this moment, with newer COVID-19 variants on the rise worldwide. During this difficult pandemic period, caregivers, families, and healthcare professionals are recommended to pay more attention to the ASD patients' health and care needs.

17.
iScience ; 27(3): 109049, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38361624

RESUMEN

Direct acting antivirals (DAAs) represent critical tools for combating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that have escaped vaccine-elicited spike-based immunity and future coronaviruses with pandemic potential. Here, we used bioluminescence imaging to evaluate therapeutic efficacy of DAAs that target SARS-CoV-2 RNA-dependent RNA polymerase (favipiravir, molnupiravir) or main protease (nirmatrelvir) against Delta or Omicron VOCs in K18-hACE2 mice. Nirmatrelvir displayed the best efficacy followed by molnupiravir and favipiravir in suppressing viral loads in the lung. Unlike neutralizing antibody treatment, DAA monotherapy regimens did not eradicate SARS-CoV-2 in mice, but combining molnupiravir with nirmatrelvir exhibited superior additive efficacy and led to virus clearance. Furthermore, combining molnupiravir with caspase-1/4 inhibitor mitigated inflammation and lung pathology whereas combining molnupiravir with COVID-19 convalescent plasma demonstrated synergy, rapid virus clearance, and 100% survival. Thus, our study provides insights into in vivo treatment efficacies of DAAs and other effective combinations to bolster COVID-19 therapeutic arsenal.

18.
Pharmaceutics ; 16(2)2024 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-38399343

RESUMEN

Ischemic stroke-induced neuronal cell death leads to the permanent impairment of brain function. The Fas-mediating extrinsic apoptosis pathway and the cytochrome c-mediating intrinsic apoptosis pathway are two major molecular mechanisms contributing to neuronal injury in ischemic stroke. In this study, we employed a Fas-blocking peptide (FBP) coupled with a positively charged nona-arginine peptide (9R) to form a complex with negatively charged siRNA targeting Bax (FBP9R/siBax). This complex is specifically designed to deliver siRNA to Fas-expressing ischemic brain cells. This complex enables the targeted inhibition of Fas-mediating extrinsic apoptosis pathways and cytochrome c-mediating intrinsic apoptosis pathways. Specifically, the FBP targets the Fas/Fas ligand signaling, while siBax targets Bax involved in mitochondria disruption in the intrinsic pathway. The FBP9R carrier system enables the delivery of functional siRNA to hypoxic cells expressing the Fas receptor on their surface-a finding validated through qPCR and confocal microscopy analyses. Through intranasal (IN) administration of FBP9R/siCy5 to middle cerebral artery occlusion (MCAO) ischemic rat models, brain imaging revealed the complex specifically localized to the Fas-expressing infarcted region but did not localize in the non-infarcted region of the brain. A single IN administration of FBP9R/siBax demonstrated a significant reduction in neuronal cell death by effectively inhibiting Fas signaling and preventing the release of cytochrome c. The targeted delivery of FBP9R/siBax represents a promising alternative strategy for the treatment of brain ischemia.

19.
Environ Monit Assess ; 196(3): 278, 2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38367088

RESUMEN

The current study investigated wild plant resources and health risk assessment along with northern Pakistan's mafic and ultramafic regions. Ethnobotanical data was collected through field visits and semi-structured questionnaire surveys conducted from local inhabitants and healers. Six potentially toxic elements (PTEs) such as lead (Pb), cadmium (Cd), nickel (Ni), chromium (Cr), manganese (Mn), and zinc (Zn) were extracted with acids and analyzed using atomic absorption spectrophotometer (AAS, Perkin Elmer-7000) in nine selected wild medicinal plants. Contamination factor (CF), pollution load index (PLI), estimated daily intake (EDI), target hazard quotient (THQ), and hazard index (HI) were used to determine the health risk assessment of the studied medicinal plants. The results showed that the selected medicinal plants were used for the treatments of cough, joint swelling, cardiovascular disorders, toothaches, diabetes, and skin pimples by the local inhabitants due to their low-cost and easy accessibility. The concentrations of Pb (3.4-53 mg kg-1), Cd (0.03-0.39 mg kg-1), Ni (17.5-82 mg kg-1), Cr (29-315 mg kg-1), Mn (20-142 mg kg-1), and Zn (7.4-64 mg kg-1) in the studied medicinal plants were found above the safe limits (except Zn) set by WHO/FAO/USEPA (1984/2010). The Pb contamination factor was significantly (p < 0.05) higher in A. modesta (7.84) and D. viscosa (6.81), and Cd contamination factor was significantly higher in C. officinalis (26.67), followed by A. modesta (8.0) mg kg-1. Based on PTE concentrations, the studied plants are considered not suitable for human consumption purposes. Pollution load index values for A. modesta, A. barbadensis, A. caudatus, A. indica, C. procera (2.93), D. viscosa (2.79), and C. officinalis (2.83), R. hastatus (3.12), and Z. armatum were observed as 1.00, 2.80, 2.29, 2.29, 2.93, 2.79, 2.83, 3.12 and 2.19, respectively. Hazard index values were in order of R. hastatus (1.32 × 10-1) ˃ C. procera (1.21 × 10-1) ˃ D. viscosa (1.10 × 10-1) ˃ A. caudatus (9.11 × 10-2) ˃ A. barbadensis (8.66 × 10-2) ˃ Z. armatum (7.99 × 10-2) ˃ A. indica (6.87 × 10-2) ˃ A. modesta (5.6 × 10-2) ˃ C. officinalis (5.42 × 10-2). The health risk index values suggested that consumption of these plants individually or in combination would cause severe health problems in the consumers. Pearson's correlation results showed a significant correlation (p ≤ 0.001) between Zn and Mn in the studied medicinal plants. The current study suggests that wild medicinal plants should be adequately addressed for PTEs and other carcinogenic pollutants before their uses in the study area. Open dumping of mining waste should be banned and eco-friendly technology like organic amendments application should be used to mitigate PTEs in the study area.


Asunto(s)
Porcelana Dental , Aleaciones de Cerámica y Metal , Metales Pesados , Plantas Medicinales , Contaminantes del Suelo , Titanio , Humanos , Cadmio , Metales Pesados/análisis , Monitoreo del Ambiente/métodos , Pakistán , Plomo , Medición de Riesgo , Contaminantes del Suelo/análisis
20.
Traffic Inj Prev ; 25(3): 472-481, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38261528

RESUMEN

OBJECTIVE: Motorcycle crashes often result in severe injuries on roads that affect people's lives physically, financially, and psychologically. These injuries could be notably harmful to drivers of all age groups. The main objective of this study is to investigate the risk factors contributing to the severity of crash injuries in different age groups. METHODS: This Objective is achieved by developing accurate machine learning (ML) based prediction models. This research examines the relationship between potential risk factors of motorcycle-associated crashes using (ML) and Shapley Additive explanations (SHAP) technique. The SHAP technique further helped interpreting ML methods for traffic injury severity prediction. It indicates the significant non-linear interactions between dependent and independent variables. The data for this study was collected from the Provincial Emergency Response Service RESCUE 1122 for the Rawalpindi region (Pakistan) over three years (from 2017 to 2020). The Synthetic Minority Oversampling Technique (SMOTE) is employed to balance injury severity classes in the pre-processing phase. RESULTS: The results demonstrate that age, gender, posted speed limit, the number of lanes, and month of the year are positively associated with severe and fatal injuries. This research also assesses how the modeling framework varies between the ML and classical statistical methods. The predictive performance of proposed ML models was assessed using several evaluation metrics, and it is found that Catboost outperformed the XGBoost, Random Forest (RF) and Multinomial Logit (MNL) model. CONCLUSION: The findings of this study will assist road users, road safety authorities, stakeholders, policymakers, and decision-makers in obtaining substantial and essential guidance for reducing the severity of crash injuries in Pakistan and other countries with prevailing conditions.


Asunto(s)
Servicios Médicos de Urgencia , Heridas y Lesiones , Humanos , Motocicletas , Accidentes de Tránsito , Factores de Riesgo , Modelos Logísticos , Heridas y Lesiones/epidemiología
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