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1.
Phys Rev Lett ; 132(3): 034001, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38307050

RESUMEN

Rotation, which stabilizes flow, can enhance the heat transfer in Rayleigh-Bénard convection (RBC) through Ekman pumping. In this Letter, we present the results of our direct numerical simulations of rotating RBC, providing a comprehensive analysis of this heat transfer enhancement relative to nonrotating RBC in the parameter space of Rayleigh number (Ra), Prandtl number (Pr), and Taylor number (Ta). We show that for a given Ra, there exists a critical Prandtl number (Pr_{cr}) below which no significant heat transfer enhancement occurs at any rotation rate, and an optimal Prandtl number (Pr_{opt}) at which maximum heat transfer enhancement occurs at an optimal rotation rate (Ta_{opt}). Notably, Pr_{cr}, Pr_{opt}, Ta_{opt}, and the maximum heat transfer enhancement all increase with increasing Ra. We also demonstrate a significant heat transfer enhancement up to Ra=2×10^{10} and predict that the enhancement would become even more pronounced at higher Ra, provided Pr is also increased commensurately.

2.
Eur Spine J ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38884807

RESUMEN

STUDY DESIGN: Prospective observational qualitative study. OBJECTIVE: Cannabis is used by patients for the treatment of chronic pain, spasticity, sleep issues or mood disorders such as anxiety and depression. Since 2018, it has been authorised in the United Kingdom for medical use as an unlicensed medicine. This study aims to determine if patients are using cannabis for the management of symptoms related to spinal cord injury, and if so, whether they are using medical or illicit cannabis. METHODS: Spinal cord injury patients from the Yorkshire Regional Spinal Injuries Centre and SPINE Community in the United Kingdom were surveyed. Participants were sent a 7-point electronic survey. All results were anonymous, and confidentiality was maintained throughout the process. RESULTS: In total, 223 patients completed the survey. Not all patients answered every question. Of those who responded 65.35% (n = 132) were paraplegic and 34.65% (n = 70) were tetraplegic. Patients were suffering from chronic pain (longer than 3 months), spasticity, loss of/difficulty in sleeping or anxiety/depression. Almost 15% (14.93%, n = 33 out of 221) used cannabis to manage their symptoms, out of those the majority used street cannabis (79.41%, n = 27 out of 34) were using street cannabis. CONCLUSION: This study demonstrates that there are spinal cord injury patients in the UK using cannabis to treat their symptoms. A majority appear to be using illicit cannabis. Given that cannabis can interact with other medications, and that the quality and content of illicit cannabis can be highly variable and at times dangerous, it is important for physicians to discuss cannabis use with their patients. This can inform prescribing and allow them to educate patients on the dangers of medical cannabis and potential alternatives.

3.
Semin Cancer Biol ; 86(Pt 3): 1158-1174, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36244530

RESUMEN

Metabolic reprogramming is an important cancer hallmark that plays a key role in cancer malignancies and therapy resistance. Cancer cells reprogram the metabolic pathways to generate not only energy and building blocks but also produce numerous key signaling metabolites to impact signaling and epigenetic/transcriptional regulation for cancer cell proliferation and survival. A deeper understanding of the mechanisms by which metabolic reprogramming is regulated in cancer may provide potential new strategies for cancer targeting. Recent studies suggest that deregulated transcription factors have been observed in various human cancers and significantly impact metabolism and signaling in cancer. In this review, we highlight the key transcription factors that are involved in metabolic control, dissect the crosstalk between signaling and transcription factors in metabolic reprogramming, and offer therapeutic strategies targeting deregulated transcription factors for cancer treatment.


Asunto(s)
Neoplasias , Factores de Transcripción , Humanos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Neoplasias/patología , Redes y Vías Metabólicas
4.
Eur Spine J ; 32(5): 1591-1597, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36966256

RESUMEN

STUDY DESIGN: Prospective observational cohort study. OBJECTIVE: To understand if serum procalcitonin (PCT) is a reliable indicator of sepsis in spinal cord injury (SCI) patients for better prognosis and earlier diagnosis when compared with other common biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells (WBC), blood culture and body temperature. METHODS: From March 2021 to August 2022, data were collected for SCI patients who developed septicaemia. In addition to neurology and admission, the following blood samples were collected on day one of infection: PCT, CRP and WBC. Linear regression analysis was performed to determine the relationship between PCT, CRP and WBC. RESULTS: A total of 27 SCI patients had an infection during their stay in the regional centre; however, only 10 developed septicaemias. 100% of SCI individuals with sepsis had elevated PCT levels, whilst 60% had elevated CRP and 30% had elevated WBC levels. There was a strong positive correlation between PCT and CRP (R2 = 0.673, CI = 95%, 5.5-22.8, p < 0.05) and a weaker positive correlation between PCT and WBC (R2 = 0.110, CI = 95%, 4.2-10.9, p < 0.05). CONCLUSION: In SCI individuals, there was a correlation between serum PCT levels and septicaemia. Alongside this, PCT appeared to be more consistent throughout the study population when compared with CRP and WBC. However, this was a preliminary study and further research is required on a larger scale.


Asunto(s)
Sepsis , Traumatismos de la Médula Espinal , Humanos , Polipéptido alfa Relacionado con Calcitonina , Calcitonina , Péptido Relacionado con Gen de Calcitonina , Estudios Prospectivos , Precursores de Proteínas , Sepsis/complicaciones , Sepsis/diagnóstico , Biomarcadores , Proteína C-Reactiva/análisis , Estudios de Cohortes , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/diagnóstico
5.
Bioorg Chem ; 121: 105671, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35168120

RESUMEN

In our efforts to identify novel chemical scaffolds for the development of antimalarial agents, a series of quinoline - imidazole hybrid compounds were synthesized and their blood-stage antimalarial activity was evaluated in both drug-sensitive and -multi drug-resistant (MDR) P. falciparum strains. The new analogs possess sub-micromolar activities against Plasmodium falciparum. Among all synthesized derivatives, 11(xxxii) exhibited significant antimalarial efficacy in-vitro against both CQ-sensitive (IC50-0.14 µM) and MDR strain (IC50- 0.41 µM) with minimal cytotoxicity and high selectivity. Structure-activity relationships revealed that Br and OMe substitutions on quinoline ring improved the antimalarial activity and selectivity index. The role of stereochemistry in the inhibitory activity was assessed by enantiomeric separation of a racemic mixture of 11(xxxii). The enantiomer (-)-11(xxxii) had potent antimalarial activity over the other isomer, with IC50 of 0.10 µM.


Asunto(s)
Antimaláricos , Antiprotozoarios , Hidroxiquinolinas , Nitroimidazoles , Quinolinas , Inhibidores de 14 alfa Desmetilasa/farmacología , Antimaláricos/química , Antiprotozoarios/farmacología , Inhibidores del Citocromo P-450 CYP3A , Imidazoles , Plasmodium falciparum , Quinolinas/química , Relación Estructura-Actividad
6.
Sensors (Basel) ; 22(1)2022 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-35009911

RESUMEN

With the advancement in technology, machine learning can be applied to diagnose the mass/tumor in the brain using magnetic resonance imaging (MRI). This work proposes a novel developed transfer deep-learning model for the early diagnosis of brain tumors into their subclasses, such as pituitary, meningioma, and glioma. First, various layers of isolated convolutional-neural-network (CNN) models are built from scratch to check their performances for brain MRI images. Then, the 22-layer, binary-classification (tumor or no tumor) isolated-CNN model is re-utilized to re-adjust the neurons' weights for classifying brain MRI images into tumor subclasses using the transfer-learning concept. As a result, the developed transfer-learned model has a high accuracy of 95.75% for the MRI images of the same MRI machine. Furthermore, the developed transfer-learned model has also been tested using the brain MRI images of another machine to validate its adaptability, general capability, and reliability for real-time application in the future. The results showed that the proposed model has a high accuracy of 96.89% for an unseen brain MRI dataset. Thus, the proposed deep-learning framework can help doctors and radiologists diagnose brain tumors early.


Asunto(s)
Neoplasias Encefálicas , Aprendizaje Profundo , Neoplasias Meníngeas , Humanos , Imagen por Resonancia Magnética , Reproducibilidad de los Resultados
7.
J Tissue Viability ; 31(4): 768-775, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35941057

RESUMEN

Pressure ulcer (PU) is a localized injury to the skin or underlying tissues usually over a bony prominence, which results due to pressure or pressure in combination with shear. It is an expensive health care problem that have deterring impact on the length of hospitalization and cause extra nursing care time. Moreover, PUs negatively impacts patients' health related quality of life. High PUs prevalence figures were found in specialized hospital units such as intensive care unit (ICU), orthopedics, surgery, and also in stroke patients in medical units. The major purpose of this study is to assess the frequency of pressure ulcers in stroke patients at Ayub teaching hospital. The methodology used for carrying out the research was cross-sectional study conducted during months of September, October, and November 2020. Questionnaire was used to collect the data and well-informed written consent was taken from the patients. A total of 120 stroke patients were initially included with the intention to study the frequency of PUs among them. Different age groups were taken but majority (48.3%) belonged to the age group 31-60 years. Maximum patients were hypertensive (65%), while few of them were diabetic (35%). From the results of proposed work, it is found that out of 120 stroke patients, 75.8% presented with ischemic stroke while 24.2% presented with hemorrhagic stroke. 8.3% that is 10 out of 120 stroke patients developed pressure ulcers of grade 1 (1.7%), grade 2 (1.7%), grade 3 (2.5%), and grade 4 (2.5%) mostly in the sacral region (6.7%) and also on ankle (0.8%), and shoulder (0.8%) respectively. Patients in the study group had unsatisfactory hygiene (6.7%) were malnourished (11.7%) and were not using preventive mattresses (79.2%). Those at the risk of developing pressure ulcers were not being repositioned (6.7%) and did not had awareness (10%). Prevention and treatment used in ward is 100%. Conclusively, the frequency of pressure ulcers in stroke patients was determined to be 8.3% and the most frequent localization was sacrum. The PU care in this hospital is appropriate but still could be improved further by improving risk assessment, prevention specially use of air mattress and patient education regarding PUs. The main objective of the study is to identify the frequency of PUs in stroke patients and to highlight various factors that would avoid PUs development.


Asunto(s)
Úlcera por Presión , Accidente Cerebrovascular , Humanos , Adulto , Persona de Mediana Edad , Úlcera por Presión/epidemiología , Úlcera por Presión/etiología , Prevalencia , Estudios Transversales , Calidad de Vida , Centros de Atención Terciaria , Hospitalización , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/epidemiología , Supuración
8.
Biochem J ; 477(18): 3625-3643, 2020 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-32893851

RESUMEN

Plasmodium falciparum, the human malaria parasite harbors a metastable proteome which is vulnerable to proteotoxic stress conditions encountered during its lifecycle. How parasite's chaperone machinery is able to maintain its aggregation-prone proteome in functional state, is poorly understood. As HSP70-40 system forms the central hub in cellular proteostasis, we investigated the protein folding capacity of PfHSP70-1 and PfHSP40 chaperone pair and compared it with human orthologs (HSPA1A and DNAJA1). Despite the structural similarity, we observed that parasite chaperones and their human orthologs exhibit striking differences in conformational dynamics. Comprehensive biochemical investigations revealed that PfHSP70-1 and PfHSP40 chaperone pair has better protein folding, aggregation inhibition, oligomer remodeling and disaggregase activities than their human orthologs. Chaperone-swapping experiments suggest that PfHSP40 can also efficiently cooperate with human HSP70 to facilitate the folding of client-substrate. SPR-derived kinetic parameters reveal that PfHSP40 has higher binding affinity towards unfolded substrate than DNAJA1. Interestingly, the observed slow dissociation rate of PfHSP40-substrate interaction allows PfHSP40 to maintain the substrate in folding-competent state to minimize its misfolding. Structural investigation through small angle x-ray scattering gave insights into the conformational architecture of PfHSP70-1 (monomer), PfHSP40 (dimer) and their complex. Overall, our data suggest that the parasite has evolved functionally diverged and efficient chaperone machinery which allows the human malaria parasite to survive in hostile conditions. The distinct allosteric landscapes and interaction kinetics of plasmodial chaperones open avenues for the exploration of small-molecule based antimalarial interventions.


Asunto(s)
Proteínas del Choque Térmico HSP40/química , Proteínas del Choque Térmico HSP72/química , Plasmodium falciparum/química , Pliegue de Proteína , Proteínas Protozoarias/química , Proteínas del Choque Térmico HSP40/genética , Proteínas del Choque Térmico HSP40/metabolismo , Proteínas del Choque Térmico HSP72/genética , Proteínas del Choque Térmico HSP72/metabolismo , Humanos , Plasmodium falciparum/genética , Plasmodium falciparum/metabolismo , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo
9.
Indian J Microbiol ; 61(2): 137-150, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33927455

RESUMEN

A total of 50 Escherichia coli were isolated from buffalo meat and their antibiotic profiling was carried out. 90% E. coli isolates showed resistant to two or more classes of 21 commonly used antibiotics. Moreover, there was also variation in resistance/sensitivity behavior towards antibiotics. Highest resistance was found to be against methicillin (84%) in the isolates followed by vancomicin (70%), sulphadiazine (68%) and cefaclor (66%), whereas, resistance was less common for kanamycin (8%) and chloramphenicol (4%). ECMB1, ECMA2, ECMA8, ECMS9 and ECMA31 strains showed highest MDR pattern with presence of bla CTX-M, qnr S and qnr B resistant genes. ECMB1 strain was resistant to 14 antibiotics belonging to 7 different classes. Therefore, ECMB1 was selected for further studies. Sodium Alginate Film incorporated with 10, 20, and 30% ethanolic extract of Syzygium cumini (EESC) were formulated and characterized using state-of-art techniques. A dose-dependent antibacterial activity against E. coli ECMB1 was recorded by the films made from EESC (EESCF). The growth kinetics of E. coli strain ECMB1 showed 9% decrease in log CFU when it was cultured in 30% EESCF as compared to control cells after 12 h of growth. Present finding highlight the efficacy and possible use of EESCF as meat packaging film to prevent food spoilage caused by MDR bacteria.

10.
Plant Dis ; 2020 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-33044144

RESUMEN

Tomato is a popular vegetable crop that is cultivated worldwide. It is also one of the most important crops in Saudi Arabia. In 2017, the area in which tomato was grown in Saudi Arabia was estimated to be 13317 ha and produced 306389 tons. Al Kharj Governorate in Riyadh region contributes the highest production of greenhouse tomatoes in Saudi Arabia (Ministry of Env. WTR & AGRI., 2017). In fall 2015, striking virus-like symptoms (mottling, leaf rolling, yellowing, and deformation, black strip on the stem, cracking on fruits, deformation, mottling, and mummification with severe yield losses) were observed on greenhouse tomato plants in several farms in Al Kharj Governorate. Samples were collected within the period of fall 2015 and the summer of 2017. The collected samples were tested serologically using enzyme linked immunosorbent assay (ELISA) for identification of the causal agent(s) using kits and protocols from AC Diagnostics Inc (Fayetteville, Arkansas, UAS). Out of 18 common tomato viruses tested, 14 viruses were detected in tomato plants in the region. The greatest concern was the presence of Tomato black ring virus (TBRV) as this was the first detection in Saudi Arabia and displayed the highest frequency of detection among all other detected viruses. Seventy-one out of the 135 tested samples were positive for TBRV. To confirm the presence of TBRV in the infected tomato samples, total RNA was extracted from positive samples and tested by RT-PCR with the newly designed primer pair F-TBRV (5'-GCAAACCAACGCTCTATGTTGT-3')/R-TBRV (5'-AGAGCCAAACTGGAATGGTAGG-3') that is specific to the CP gene of TBRV. RT-PCR products of 978 bp in length were successfully obtained from the naturally infected tomato plants. One of the detected isolates was used to inoculate Chenopodium amaranticolor with the aim of obtaining a pure isolate from single local lesions that could be later used for propagation and maintenance in Nicotiana tabacum. A host range experiment was conducted using mechanical inoculation with the single-lesion isolate of TBRV on four replicates of 14 different plant species in parallel with healthy controls (Brunt et. al. 1996). Three weeks post-inoculation, varying reactions and symptoms ranging from local lesion to plant death, depending on host species, were observed on the tested plants (Supplementary Table 1). Host range results were largely similar to those reported in previous studies (Sneideris et al. 2012, and Rymelska et al. 2013). The presence of TBRV was confirmed both by ELISA and RT-PCR. Nucleotide sequences obtained from PCR products of selected samples were submitted to the GenBank and assigned the following accession numbers: MT274656, MT274657, and MT274658. Saudi isolates of TBRV were found to share 99-100% of their nucleotide sequences. They had the highest similarity of 98% with the Polish isolates (MG458221 and KX977561) and the lowest similarity of 85% with isolates from Lithuania (KF678369, and KF678370). To the best of our knowledge, this is the first report of occurrence of TBRV in Saudi Arabia. Since this virus is transmitted by seeds, it may have entered through imported seeds and spread in greenhouses through mechanical means. A survey of the different agricultural regions is encouraged to determine the incidence, distribution, and damage induced by this virus in Saudi Arabia.

11.
J Oral Maxillofac Surg ; 77(9): 1752-1759, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31026419

RESUMEN

PURPOSE: This study aimed to evaluate the effectiveness of submucosal injection of tramadol in treating postoperative pain after surgical extraction of impacted mandibular third molars. MATERIALS AND METHODS: We implemented a randomized controlled trial. The sample was divided into 30 cases (receiving tramadol injection) and 30 controls (receiving saline solution injection). Patients were asked to complete a visual analog pain scale (VAPS) at 0.5, 1, 2, 4, 6, 12, 24, and 48 hours. Patients also were asked to note the time at which rescue analgesics were taken, as well as the total number of analgesics taken. The VAPS data were analyzed using the unpaired Student t test. Other variables were analyzed using analysis of variance with the Bonferroni t test and Pearson χ2 test. P < .05 was considered significant. RESULTS: A total of 60 patients, 32 men and 28 women (mean age, 27.78 years; age range, 19 to 45 years), took part in this study. Postoperative pain scores, as recorded on the VAPS, were significantly lower in the tramadol group, with the differences being statistically significant at 0.5, 1, 2, 4, and 6 hours (P < 0.001, P = .006, P < 0.001, P < 0.001, and P < 0.001, respectively). The mean time at which the first tablet was taken and the total number of tablets taken by the tramadol group also were statistically significant (P = .001 for both). CONCLUSIONS: The results suggest that submucosal injection of tramadol has a significant effect on postoperative pain control after surgical extraction of impacted third molars.


Asunto(s)
Analgésicos Opioides , Dolor Postoperatorio , Extracción Dental , Diente Impactado , Tramadol , Adulto , Analgésicos Opioides/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tercer Molar/cirugía , Dimensión del Dolor , Dolor Postoperatorio/tratamiento farmacológico , Tramadol/administración & dosificación , Adulto Joven
12.
BMC Ophthalmol ; 18(1): 317, 2018 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-30541489

RESUMEN

BACKGROUND: This report highlights a rare case of simultaneous bilateral blindness due to posterior ischemic optic neuropathy. Typically, ophthalmic involvement in giant cell arteritis is monocular or sequential ischemia of the anterior portion of the optic nerve, and less frequently simultaneous. CASE PRESENTATION: An 80-year-old Saudi male came with a history of simultaneous bilateral vision loss 5 days prior to presentation. The exam showed dilated non-reactive pupils, no light perception in both eyes, and normal fundus exam. C-reactive protein and erythrocyte sedimentation rate levels were high Magnetic resonance imaging and magnetic resonance angiography of the brain showed a right posterior optic nerve lesion and absence of flow in both ophthalmic arteries respectively. A left temporal artery biopsy confirmed giant cell arteritis. CONCLUSION: The presentation of GCA can be atypical and patients may present with simultaneous blindness. Bilateral simultaneous PION does not exclusively occur in a post surgical setting, emphasizing the importance of decreasing the threshold of suspicion of similar cases to avoid further neurological complications.


Asunto(s)
Ceguera/etiología , Arteritis de Células Gigantes/complicaciones , Neuropatía Óptica Isquémica/complicaciones , Anciano de 80 o más Años , Humanos , Masculino
14.
Biochemistry ; 56(51): 6691-6699, 2017 12 26.
Artículo en Inglés | MEDLINE | ID: mdl-29182860

RESUMEN

The unique occurrence of G-quadruplexes in the AT-rich genome of human malaria parasite Plasmodium falciparum provides hints about their critical roles in parasite survival, pathogenesis, and host immune evasion. An intriguing question is whether these noncanonical structures can serve as molecular targets for small molecule-based interventions against malaria. In this study, we have investigated the pharmacological targeting of G-quadruplexes for parasite inhibition. We observed that bisquinolinium derivatives of 1,8-naphthyridine and pyridine affected the stability and molecular recognition properties of G-quadruplexes in telomeric and subtelomeric regions in P. falciparum. Parasite inhibition and cytotoxicity assays revealed that these ligands effectively inhibit parasite growth with minimal toxic effects in human cells. G-quadruplex interacting ligands caused degeneration and shortening of parasite telomeres. Ligand-induced perturbations in telomere homeostasis also affected transcriptional state of the subtelomeric region harboring antigenic variation genes. Taken together, our results suggest that quadruplex-ligand interaction disturbs telomeric/subtelomeric chromatin organization and induces DNA damage that consequently leads to parasite death. Our findings also draw attention to the striking differences in telomere dynamics in the protozoan parasite and human host that can be exploited for selective targeting of the telomeric quadruplex of the parasite as a potential antimalarial strategy.


Asunto(s)
Antimaláricos/farmacología , G-Cuádruplex/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Animales , Línea Celular , Daño del ADN , Humanos , Concentración 50 Inhibidora , Ligandos , Plasmodium falciparum/genética , Telómero/efectos de los fármacos
15.
Front Digit Health ; 6: 1195697, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38419806

RESUMEN

Objectives: Telehealth has become increasingly important in achieving universal health coverage. It offers doctors and their patients' convenience, including providing quality care at reduced costs. During the coronavirus disease (COVID)-19 pandemic, telehealth has been a vital tool for remote healthcare services. This study aimed to assess the satisfaction of adult and pediatric neurologists and neurosurgeons using telehealth, during the COVID-19 pandemic in Saudi Arabia. Methods: This study had 348 participants. It was conducted among adult and pediatric neurologists and neurosurgeons using telehealth technology at their clinics between February and June 2021. The self-administered questionnaire included sociodemographic data, behavior in using telehealth, and an assessment of satisfaction with telehealth; the SPSS Windows software version 26 was used to analyze the data. Results: The most common age group was 25-34 years (42.8%), with men dominating (68.4%). The mean satisfaction score was 25.9 (SD 3.91) out of 33 points, with 90.2% of respondents satisfied with telehealth and 9.8% dissatisfied. Working in an academic center or private hospital, being a first-time telehealth user, using messages as a telehealth method, and using telehealth daily were associated with increased satisfaction with telehealth use. Conclusion: The satisfaction of adult and pediatric neurologists and neurosurgeons with telehealth was high. Although physicians still preferred face-to-face interviews, they recognized the benefits of telehealth in strengthening the patient-provider relationship, improving productivity, and integrating into daily workflows. The satisfaction levels align with past studies, but physical examination needs should be considered. Telehealth is suitable for follow-up visits and varies across subspecialties.

16.
Medicine (Baltimore) ; 103(25): e38646, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38905380

RESUMEN

The aim of this study is to estimate the normal cross-sectional area and diameter of the stellate ganglion (SG) by ultrasound (US) in healthy adults. The study sample included 80 stellate ganglia in 40 participants (15 males, 25 females), mean age 38 years, mean height 162.5 cm, mean weight 67.8 kg, mean body mass index 25.4 kg/m2. Two radiologists separately obtained US images of the bilateral SG. Each participant was scanned 3 times bilaterally to assess for intra-observer reliability. The mean diameter of the SG was 1 mm (range: 0.1-2). The mean CSA of the bilateral SG was 1.3 mm2 (range: 0.6-3.9). The SG diameter positively correlated with age. Our study demonstrates the ability of US to image the SG and estimate its normal diameter and CSA. Knowledge of how to identify and measure the SG during ultrasound-guided procedures would be expected to decrease the risk of associated complications and help establish normal reference values.


Asunto(s)
Ganglio Estrellado , Ultrasonografía , Humanos , Masculino , Femenino , Adulto , Ganglio Estrellado/diagnóstico por imagen , Ultrasonografía/métodos , Persona de Mediana Edad , Valores de Referencia , Voluntarios Sanos , Adulto Joven , Reproducibilidad de los Resultados , Variaciones Dependientes del Observador
17.
Elife ; 122023 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-37158595

RESUMEN

Potassium efflux via the two-pore K+ channel TWIK2 is a requisite step for the activation of NLRP3 inflammasome, however, it remains unclear how K+ efflux is activated in response to select cues. Here, we report that during homeostasis, TWIK2 resides in endosomal compartments. TWIK2 is transported by endosomal fusion to the plasmalemma in response to increased extracellular ATP resulting in the extrusion of K+. We showed that ATP-induced endosomal TWIK2 plasmalemma translocation is regulated by Rab11a. Deleting Rab11a or ATP-ligated purinergic receptor P2X7 each prevented endosomal fusion with the plasmalemma and K+ efflux as well as NLRP3 inflammasome activation in macrophages. Adoptive transfer of Rab11a-depleted macrophages into mouse lungs prevented NLRP3 inflammasome activation and inflammatory lung injury. We conclude that Rab11a-mediated endosomal trafficking in macrophages thus regulates TWIK2 localization and activity at the cell surface and the downstream activation of the NLRP3 inflammasome. Results show that endosomal trafficking of TWIK2 to the plasmalemma is a potential therapeutic target in acute or chronic inflammatory states.


Asunto(s)
Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Ratones , Adenosina Trifosfato/metabolismo , Transporte Biológico , Caspasa 1/metabolismo , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo
18.
Healthcare (Basel) ; 11(7)2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-37046885

RESUMEN

BACKGROUND: Vitamin B12 is one of the most important B-Vitamins that the human body needs on a daily basis, the lack of which can precipitate several neurological issues. OBJECTIVES: This systematic aimed to investigate the neurological implications of Vitamin B12 deficiency and the effects when B12 levels were corrected in susceptible individuals. METHODS: The databases PubMed-MEDLINE, Web of Science, Cochrane, and Scopus were all searched using pertinent keywords, reference searches, and citation searches. The terms used to access the database were "Cognition", "Dietary patterns", "Neurology", "Nutritional profile", and "Vitamin B12". RESULTS: Vitamin B12 was shown to noticeably improve cognition and other neurological parameters in the short term in older adults and the short-to-medium term in children; however, there was no perceived increase/improvement when the Vitamin was administered in the longer term, either alone or in conjunction with other similar nutritional interventions. CONCLUSION: Vitamin B12's role in the improvement of neurological functions over a long-term period remains somewhat inconclusive to date, as the majority of our selected control trials did not display much correlation between the two factors. However, Vitamin B12 did improve cognition levels in both children and older adults over a short course of administration.

19.
ChemMedChem ; 17(2): e202100472, 2022 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-34717044

RESUMEN

Although many quinolones have shown promise as potent antimalarials, their clinical development has been slow due to poor performance in vivo. Insights into structural modifications that can improve their therapeutic potential will be very valuable in this vibrant area of research. Our studies involving a library of quinolones which vary in substitution pattern at N1, C3, C6 and C7 positions have shown that the presence of adenine moiety at C7 can bring a noticeable improvement in activity compared to other heterocyclic groups at this location. The most potent compound emerged from this study showed IC50 values of 0.38 µM and 0.75 µM against chloroquine-sensitive and -resistant (W2) strains, respectively. Docking analysis in the Qo site of cytochrome bc1 complex revealed the contribution of a key H-bonding interaction from the adenine unit in target binding. This corroborates with compound-induced loss of mitochondrial functions. These findings not only open avenues for further exploration of antimalarial potential of adenine-modified quinolones, but also suggests broader opportunities during lead-optimization against other antimalarial targets.


Asunto(s)
Adenina/farmacología , Antimaláricos/farmacología , Malaria Falciparum/tratamiento farmacológico , Plasmodium falciparum/efectos de los fármacos , Quinolonas/farmacología , Adenina/química , Animales , Antimaláricos/síntesis química , Antimaláricos/química , Chlorocebus aethiops , Relación Dosis-Respuesta a Droga , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Quinolonas/síntesis química , Quinolonas/química , Relación Estructura-Actividad , Células Vero
20.
J Infect Dev Ctries ; 16(12): 1933-1938, 2022 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-36753653

RESUMEN

INTRODUCTION: Acute transverse myelitis is an uncommon inflammatory, intramedullary, disorder of the spinal cord. Spastic paraplegia, impaired sphincter functions, and sensory loss, with sensory level, are the clinical manifestations of this devastating disorder. The utilization of magnetic resonant imaging (MRI) contributes to the surge in the diagnosis of more ATM cases. Although the causes of ATM are numerous, both Mycoplasma pneumoniae and Schistosoma mansoni are uncommon causes and their co-existence in the same patient has not been reported before in Saudi Arabia. CASE: We report a 25-year-old ATM male patient presented with a history of sudden onset severe low back pain. Within four hours from the onset of the back pain, he became completely paraplegic with impaired functions of the bowel and urinary bladder sphincter. Furthermore, he lost all modalities of sensory functions in the lower limbs. His examination revealed spastic complete paraplegia with sensory level at T6. Clinical neurological examination revealed normal upper limbs and brain functions. The MRI of the cervico-dorsal spine showed extensive longitudinal hyperintense lesion extending from the upper cervical segments to the lower dorsal segments (extensive longitudinal transverse myelitis). A post-infectious immune-mediated predisposition was highly suspected due to the very high titers of anti-Mycoplasma pneumoniae IgM and IgG that were detected. The immunosuppressant therapy did not improve his paraplegia. A spinal cord biopsy revealed the presence of several Schistosoma mansoni ova surrounded by chronic inflammatory reactions and reactive gliosis. CONCLUSIONS: Both Mycoplasma pneumoniae and Schistosoma mansoni should be investigated in cases with extensive longitudinal ATM.


Asunto(s)
Coinfección , Mielitis Transversa , Esquistosomiasis mansoni , Animales , Humanos , Masculino , Adulto , Mielitis Transversa/diagnóstico por imagen , Mielitis Transversa/tratamiento farmacológico , Mycoplasma pneumoniae , Schistosoma mansoni , Coinfección/diagnóstico , Coinfección/complicaciones , Imagen por Resonancia Magnética/efectos adversos , Esquistosomiasis mansoni/complicaciones , Paraplejía/complicaciones , Paraplejía/terapia , Inflamación
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