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1.
Pediatr Rheumatol Online J ; 22(1): 48, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678299

RESUMO

BACKGROUND: Measurement of the circulating levels of long-non-coding RNAs (lncRNAs) in lupus nephritis (LN) patients could dramatically explore more insights about the disease pathogenesis. Hence, we aimed to quantify the level of expression of CTC-471J1.2 and NeST in LN patients and to correlate it with the disease activity. METHOD: This case-control study was conducted on a group of children with juvenile LN attending to Mansoura University Children's Hospital (MUCH). Demographics, clinical, and laboratory findings were collected besides the measurement of lncRNAs by quantitative real-time PCR. RESULTS: The expression level of lncRNAs-CTC-471J1.2 was significantly down-regulated in children with active LN versus inactive cases or controls. In contrast, the NeST was significantly up-regulated in active LN cases. A significant correlation was found between CTC-471J1.2 expression and LN activity parameters. Additionally, both lncRNAs showed a reasonable sensitivity and specificity in differentiation of active LN. A regression analysis model revealed that CTC-471J1.2 and NeST were independent predictors of active nephritis. CONCLUSION: The expression level of circulatory lncRNAs-CTC-471J1.2 and NeST can be used as sensitive and specific biomarkers for active LN. Furthermore, both could serve as predictors for nephritis activity.


Assuntos
Nefrite Lúpica , RNA Longo não Codificante , Nefrite Lúpica/genética , Nefrite Lúpica/sangue , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/sangue , Estudos de Casos e Controles , Feminino , Criança , Masculino , Fatores de Risco , Adolescente , Epigênese Genética , Biomarcadores/sangue , Biomarcadores/metabolismo
2.
Asian Pac J Cancer Prev ; 25(4): 1433-1440, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38680005

RESUMO

OBJECTIVE: aim of this study was to examine the synergistic effect between the antibacterial drug ciprofloxacin and the natural compound laetrile on esophageal cancer cells, specifically focusing on their combined cytotoxic effect. METHODS: The combined cytotoxic effects of two alternative incubation durations (24 and 72 hours) were studied using an esophageal cancer cell line.  Ciprofloxacin, laetrile, and their combinations were tested at concentrations ranging from 1 to 1000 micrograms/milliliter, to enhance the safety of the combination, the concentrations of the combination constituents were reduced by half compared to when they are used individually, the combination index was then calculated to estimate the components' possible synergistic effects. RESULT: The results indicate that the combined cytotoxicity of ciprofloxacin and laetrile was greater than the cytotoxicity of either ciprofloxacin or laetrile alone, the combination cytotoxicity increased with higher concentrations and longer incubation periods, in other words, the cytotoxicity pattern of the combination was time-dependent (cell-cycle specific), and concentration dependent, (cell-cycle non-specific). CONCLUSION: The study found that the combination of ciprofloxacin and laetrile had a greater inhibitory effect on the growth of esophageal cancer cells compared to ciprofloxacin or laetrile alone. This suggests a synergistic effect between the components of the mixture, which can be attributed to a complementary mechanism between the ingredients in the combination.


Assuntos
Proliferação de Células , Ciprofloxacina , Sinergismo Farmacológico , Neoplasias Esofágicas , Humanos , Ciprofloxacina/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Proliferação de Células/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Células Tumorais Cultivadas , Apoptose/efeitos dos fármacos , Antibacterianos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
3.
Obes Facts ; 17(3): 274-285, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38484714

RESUMO

INTRODUCTION: Management of obesity is challenging for both patients and healthcare workers. Considering the low success rate of current interventions, this study aimed to explore the prevalence and associated factors of night eating syndrome (NES), insomnia, and psychological distress among individuals with obesity in order to plan comprehensive obesity management interventions. METHODS: A cross-sectional study on a convenient sample from five primary healthcare centers in Port Said, Egypt, was conducted from November 2020 to March 2021. Sociodemographic and clinical characteristics were collected in addition to the assessment of NES, insomnia, and psychological distress using the Arabic versions of the Night Eating Diagnostic Questionnaire (NEQ), the Insomnia Severity Index (ISI), and the Patient Health Questionnaire-4 (PHQ-4) scales, respectively. Associations of NES, insomnia, and psychological distress were assessed by multiple regression analysis. We performed Bonferroni adjustments for multiple comparisons. RESULTS: We included 425 participants with obesity with a mean age of 45.52 ± 6.96 years. In all, 54.4% were females and the mean body mass index (BMI) was 35.20 ± 4.41 kg/m2. The prevalence rates of NES, insomnia, and psychological distress were 21.6% (95% CI: 17.7-25.6%), 15.3% (95% CI: 11.9-18.7%), and 18.8% (95% CI: 15.1-22.6%), respectively. NES was significantly associated with younger age (OR 0.974, p = 0.016), physical inactivity (OR 0.485, p = 0.010), insomnia (OR 2.227, p = 0.014), and psychological distress (OR 2.503, p = 0.002). Insomnia showed strong associations with NES (OR 2.255, p = 0.015) and psychological distress (OR 5.990, p < 0.001). Associated factors of psychological distress symptoms included insomnia (OR 6.098, p < 0.001) and NES (OR 2.463, p = 0.003). CONCLUSION: The prevalence rates of NES, insomnia, and psychological distress were high among primary care patients with obesity, and these conditions were interrelated. Optimal obesity management necessitates individualized and targeted multidisciplinary care plans that take into consideration individual patients' mental, behavioral, and dietary habits needs.


Assuntos
Síndrome do Comer Noturno , Obesidade , Atenção Primária à Saúde , Angústia Psicológica , Distúrbios do Início e da Manutenção do Sono , Humanos , Estudos Transversais , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Distúrbios do Início e da Manutenção do Sono/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Obesidade/psicologia , Obesidade/epidemiologia , Prevalência , Adulto , Síndrome do Comer Noturno/epidemiologia , Síndrome do Comer Noturno/psicologia , Egito/epidemiologia , Inquéritos e Questionários , Índice de Massa Corporal , Estresse Psicológico/epidemiologia
4.
Cancer Lett ; 588: 216783, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38462034

RESUMO

Inhibition of K-RAS effectors like B-RAF or MEK1/2 is accompanied by treatment resistance in cancer patients via re-activation of PI3K and Wnt signaling. We hypothesized that myotubularin-related-protein-7 (MTMR7), which inhibits PI3K and ERK1/2 signaling downstream of RAS, directly targets RAS and thereby prevents resistance. Using cell and structural biology combined with animal studies, we show that MTMR7 binds and inhibits RAS at cellular membranes. Overexpression of MTMR7 reduced RAS GTPase activities and protein levels, ERK1/2 phosphorylation, c-FOS transcription and cancer cell proliferation in vitro. We located the RAS-inhibitory activity of MTMR7 to its charged coiled coil (CC) region and demonstrate direct interaction with the gastrointestinal cancer-relevant K-RASG12V mutant, favouring its GDP-bound state. In mouse models of gastric and intestinal cancer, a cell-permeable MTMR7-CC mimicry peptide decreased tumour growth, Ki67 proliferation index and ERK1/2 nuclear positivity. Thus, MTMR7 mimicry peptide(s) could provide a novel strategy for targeting mutant K-RAS in cancers.


Assuntos
Neoplasias , Proteínas Tirosina Fosfatases não Receptoras , Animais , Humanos , Camundongos , Peptídeos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/genética , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Transdução de Sinais
5.
Brain ; 147(5): 1622-1635, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38301270

RESUMO

Cholesterol homeostasis is impaired in Alzheimer's disease; however, attempts to modulate brain cholesterol biology have not translated into tangible clinical benefits for patients to date. Several recent milestone developments have substantially improved our understanding of how excess neuronal cholesterol contributes to the pathophysiology of Alzheimer's disease. Indeed, neuronal cholesterol was linked to the formation of amyloid-ß and neurofibrillary tangles through molecular pathways that were recently delineated in mechanistic studies. Furthermore, remarkable advances in translational molecular imaging have now made it possible to probe cholesterol metabolism in the living human brain with PET, which is an important prerequisite for future clinical trials that target the brain cholesterol machinery in Alzheimer's disease patients-with the ultimate aim being to develop disease-modifying treatments. This work summarizes current concepts of how the biosynthesis, transport and clearance of brain cholesterol are affected in Alzheimer's disease. Further, current strategies to reverse these alterations by pharmacotherapy are critically discussed in the wake of emerging translational research tools that support the assessment of brain cholesterol biology not only in animal models but also in patients with Alzheimer's disease.


Assuntos
Doença de Alzheimer , Encéfalo , Colesterol , Desenvolvimento de Medicamentos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Humanos , Colesterol/metabolismo , Encéfalo/metabolismo , Animais , Desenvolvimento de Medicamentos/métodos
6.
J Family Community Med ; 31(1): 16-24, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38406223

RESUMO

BACKGROUND: Health coaching effectively improves hypertension self-care activities and the control of blood pressure (BP) in hypertensive patients. Studies on the effects of health coaching on patients in primary care with uncontrolled hypertension in developing countries are limited. In this study, the effectiveness of health coaching on hypertension self-care and BP control was assessed in patients who have uncontrolled hypertension compared to standard care in Egypt. MATERIALS AND METHODS: Our quasi-experimental study included control and intervention groups. The intervention group included 70 participants who received health coaching sessions (face-to-face and by telephone) besides the standard care, whereas the control group included 71 participants who only received the standard care. The study was conducted between July 2020 and November 2021. The participants were recruited from three primary healthcare settings in the Port Said Governorate. Personal and medical history, BP measurements, and hypertension self-care activity level effects (H-SCALE) were obtained. Paired-t-test was used to assess the changes in BP measurement, and H-SCALE score before and after receiving the health coaching. McNemar's test was used to assess changes in controlled BP and optimal hypertension self-care activities between control and health coached groups. Multiple logistic regression analysis assessed the predictors of better BP control. RESULTS: Health coaching resulted in more controlled BP (51.4%, P < 0.001) compared to the delivery of only usual care (11.3%, P = 0.008). The intervention showed a significant promotion in hypertension self-care activities, including medication usage (P < 0.001), low-salt diet (P < 0.001), and weight management (P < 0.001). The H-SCALE score mean change was the only predictor for BP control (odds ratio 1.057, P = 0.048) in the intervention group after 6 months. CONCLUSION: Intervention including traditional health coaching and phone calls is a beneficial modality for the promotion of hypertension self-care and improvement of BP control in primary care patients with uncontrolled hypertension.

7.
Virol J ; 21(1): 27, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263160

RESUMO

BACKGROUND: Since the emergence of the COVID-19 infection in China, it has caused considerable morbidity, mortality, and economic burden. It causes the vast majority of clinical manifestations, ranging from mild or even no symptoms to severe respiratory failure. There are many risk factors for severe COVID-19, such as old age, male gender, and associated comorbidities. A major role for genetic factors may exist. The SARS-CoV-2 virus enters the cell primarily through ACE2 receptors. rs2285666 is one of many polymorphisms found in the ACE2 receptor gene. To enable endosome-independent entry into target cells, the transmembrane protease serine-type 2 (TMPRSS2) is necessary to cleave the virus' spike (S) glycoprotein. TMPRSS2 is characterized by an androgen receptor element. The rs12329760 polymorphism in TMPRSS2 may explain different genetic susceptibilities to COVID-19. METHOD: This cross-sectional study was held in Mansoura University Hospitals during the period from June 2020 to April 2022 on patients who had mild and severe COVID-19. Demographic, clinical, and laboratory data were collected, and the TaqMan real-time polymerase chain was used for allelic discrimination in the genotyping of rs2285666 and rs12329760. RESULTS: This study included 317 Egyptian patients, aged from 0.2 to 87 years. Males were 146, while females were 171. They were divided into mild and severe groups (91 and 226 patients, respectively) based on their clinical symptoms. There was a significant association between COVID-19 severity and male gender, hypertension, diabetes mellitus, and high CRP. The genotype and allele frequency distributions of the ACE2 rs2285666 polymorphism showed no significant association with the severity of COVID-19 in both. In contrast, in TMPRSS2 rs12329760 minor T allele and CT, TT genotypes were significantly associated with a reduced likelihood of developing severe COVID-19. CONCLUSION: Our study indicates that the ACE2 rs2285666 polymorphism is not related to the severity of COVID-19, whether genotypes or alleles. In TMPRSS2 rs12329760, the dominant model and T allele showed significantly lower frequencies in severe cases, with a protective effect against severity. The discrepancies with previous results may be due to variations in other ACE2 receptor-related genes, inflammatory mediators, and coagulation indicators. Haplotype blocks and differences in racial makeup must be taken into consideration. Future research should be done to clarify how ethnicity affects these polymorphisms and how other comorbidities combine to have an additive effect.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Feminino , Humanos , Masculino , Estudos Transversais , Egito , SARS-CoV-2 , Serina Endopeptidases
8.
Diabetol Int ; 15(1): 67-75, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38264221

RESUMO

Objectives: To evaluate the association of diabetes treatment satisfaction and trust in family physicians with glycemic control among primary care patients with type 2 diabetes mellitus. Methods: A cross-sectional study on 319 patients with type 2 diabetes mellitus from five primary healthcare centers in Egypt. Data were collected from February to August 2021 using a structured questionnaire that contained six parts: sociodemographic data, disease profile, the Diabetes Treatment Satisfaction Questionnaire (DTSQ), 8-item Morisky Medication Adherence Scale (MMAS-8), self-reported medication knowledge questionnaire (MKQ), and revised healthcare relationship trust scale (HCR). Multiple linear regression analysis was used to assess predictors of treatment satisfaction, physician trust, and HbA1c level. P values less than 0.05 were considered significant. Results: The mean age was 59.66 years (± 7.87 years) and 55.17% were females. Multiple linear regression analysis for predicting HbA1c showed that HbA1c level was lower in patients with higher treatment satisfaction scores (ß = - 0.289, p < 0.001) and higher medication adherence scores (ß = - 0.198, p = 0.001). Treatment satisfaction scores were positively predicted by higher physician trust scores (ß = 0.301, p < 0.001), increased medication adherence scores (ß = 0.160, p = 0.002), and longer duration of diabetes (ß = 0.226, p < 0.001). Positive predictors for physician trust included HbA1c level (ß = 0.141, p = 0.012), medication knowledge (ß = 0.280, p < 0.001), diabetes treatment satisfaction (ß = 0.366, p < 0.001) and medication adherence (ß = 0.146, p = 0.011). Conclusion: Optimizing diabetes treatment satisfaction and physician trust could have favorable associations with medication adherence and medication knowledge with a possible improvement in glycemic control. Family physicians should incorporate patients reported outcomes alongside traditional clinical measures in evaluating diabetes management in primary care.

9.
Eur J Neurosci ; 59(2): 283-297, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38043936

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, leading to various motor and non-motor symptoms. Several cellular and molecular mechanisms such as alpha-synuclein (α-syn) accumulation, mitochondrial dysfunction, oxidative stress and neuroinflammation are involved in the pathogenesis of this disease. MicroRNAs (miRNAs) play important roles in post-transcriptional gene regulation. They are typically about 21-25 nucleotides in length and are involved in the regulation of gene expression by binding to the messenger RNA (mRNA) molecules. miRNAs like miR-221 play important roles in various biological processes, including development, cell proliferation, differentiation and apoptosis. miR-221 promotes neuronal survival against oxidative stress and neurite outgrowth and neuronal differentiation. Additionally, the role of miR-221 in PD has been investigated in several studies. According to the results of these studies, (1) miR-221 protects PC12 cells against oxidative stress induced by 6-hydroxydopamine; (2) miR-221 prevents Bax/caspase-3 signalling activation by stopping Bim; (3) miR-221 has moderate predictive power for PD; (4) miR-221 directly targets PTEN, and PTEN over-expression eliminates the protective action of miR-221 on p-AKT expression in PC12 cells; and (5) miRNA-221 controls cell viability and apoptosis by manipulating the Akt signalling pathway in PD. This review study suggested that miR-221 has the potential to be used as a clinical biomarker for PD diagnosis and stage assignment.


Assuntos
MicroRNAs , Doença de Parkinson , Ratos , Animais , Humanos , Doença de Parkinson/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose , Neurônios Dopaminérgicos/metabolismo , Biomarcadores/metabolismo
10.
ACS Chem Neurosci ; 14(24): 4323-4334, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38060344

RESUMO

The N-methyl-d-aspartate receptor (NMDAR) subtype 2B (GluN1/2B) is implicated in various neuropathologies. Given the lack of a validated radiofluorinated positron emission tomography (PET) probe for the imaging of GluN1/2B receptors, we comprehensively investigated the enantiomers of [18F]OF-NB1 in rodents. Particularly, the (R)- and (S)- enantiomers were evaluated using in silico docking, in vitro autoradiography, in vivo PET imaging, and ex vivo biodistribution studies. A select panel of GluN1/2B antagonists (CP-101,606, CERC-301, and eliprodil) and the off-target sigma-1 receptor ligands (fluspidine and SA4503) were used to determine the specificity and selectivity of the tested enantiomers. Additionally, a nonmetal-mediated radiofluorination strategy was devised that harnesses the potential of diaryliodoniums in the nucleophilic radiofluorination of nonactivated aromatic compounds. Both enantiomers exhibited known GluN1/2B binding patterns; however, the R-enantiomer showed higher GluN1/2B-specific accumulation in rodent autoradiography and higher brain uptake in PET imaging experiments compared to the S-enantiomer. Molecular simulation studies provided further insights with respect to the difference in binding, whereby a reduced ligand-receptor interaction was observed for the S-enantiomer. Nonetheless, both enantiomers showed dose dependency when two different doses (1 and 5 mg/kg) of the GluN1/2B antagonist, CP-101,606, were used in the PET imaging study. Taken together, (R)-[18F]OF-NB1 appears to exhibit the characteristics of a suitable PET probe for imaging of GluN2B-containing NMDARs in clinical studies.


Assuntos
Receptores de N-Metil-D-Aspartato , Roedores , Animais , Roedores/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Distribuição Tecidual , Tomografia por Emissão de Pósitrons/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo
11.
Asian Pac J Cancer Prev ; 24(12): 4329-4337, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38156870

RESUMO

AIM: This study aimed to evaluate the inhibitory effect of laetrile, vinblastine, and their mixture on cervical cancer cells and probe potential synergistic consequences. METHOD: The study scrutinized the inhibitory impact of laetrile vinblastine and their mixture on the growth of human cervical cancer cells (Hela cancer cell line). The cells were incubated for 24, 48, and 72 hours with concentrations varying from 1 microgram to 10,000 micrograms of each substance. RESULT: study results showed, the combination of vinblastine and laetrile effectively reduced the viability of human cervical cancer cells. This effect was stronger than the individual cytotoxic effects of each compound. The results suggest that the cytotoxicity of the vinblastine and laetrile combination increases with higher concentrations of the compounds. Additionally, the study revealed a synergistic effect between the mixture ingredients, particularly at the lowest and highest concentrations during the 24 and 72-hour incubation periods. CONCLUSION: The antiproliferative effect of (the combination of laetrile and vinblastine) was greater than the antiproliferative effect of either compound used alone, suggesting a synergistic relationship between the two.


Assuntos
Amigdalina , Neoplasias do Colo do Útero , Feminino , Humanos , Vimblastina/farmacologia , Amigdalina/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Apoptose , Células HeLa , Proliferação de Células
12.
J Med Chem ; 66(23): 16018-16031, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-37979148

RESUMO

GluN2B subunit-containing N-methyl-d-aspartate (NMDA) receptors have been implicated in various neurological disorders. Nonetheless, a validated fluorine-18 labeled positron emission tomography (PET) ligand for GluN2B imaging in the living human brain is currently lacking. The aim of this study was to develop a novel synthetic approach that allows an enantiomerically pure radiosynthesis of the previously reported PET radioligands (R)-[18F]OF-NB1 and (S)-[18F]OF-NB1 as well as to assess their in vitro and in vivo performance characteristics for imaging the GluN2B subunit-containing NMDA receptor in rodents. A novel synthetic approach was successfully developed, which allows for the enantiomerically pure radiosynthesis of (R)-[18F]OF-NB1 and (S)-[18F]OF-NB1 and the translation of the probe to the clinic. While both enantiomers were selective over sigma2 receptors in vitro and in vivo, (R)-[18F]OF-NB1 showed superior GluN2B subunit specificity by in vitro autoradiography and higher volumes of distribution in the rodent brain by small animal PET studies.


Assuntos
Tomografia por Emissão de Pósitrons , Receptores de N-Metil-D-Aspartato , Animais , Humanos , Receptores de N-Metil-D-Aspartato/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Radioisótopos de Flúor
13.
ACS Chem Neurosci ; 14(20): 3752-3760, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37788055

RESUMO

The cannabinoid type 2 receptor (CB2) has been implicated in a variety of central and peripheral inflammatory diseases, prompting significant interest in the development of CB2-targeted diagnostic and therapeutic agents. A validated positron emission tomography (PET) radioligand for imaging CB2 in the living human brain as well as in peripheral tissues is currently lacking. As part of our research program, we have recently identified the trisubstituted pyridine, [18F]RoSMA-18-d6, which proved to be highly suitable for in vitro and in vivo mapping of CB2 in rodents. The aim of this study was to assess the performance characteristics of [18F]RoSMA-18-d6 in nonhuman primates (NHPs) to pave the way for clinical translation. [18F]RoSMA-18-d6 was synthesized from the respective tosylate precursor according to previously reported procedures. In vitro autoradiograms with NHP spleen tissue sections revealed a high binding of [18F]RoSMA-18-d6 to the CB2-rich NHP spleen, which was significantly blocked by coincubation with the commercially available CB2 ligand, GW405833 (10 µM). In contrast, no specific binding was observed by in vitro autoradiography with NHP brain sections, which was in agreement with the notion of a CB2-deficient healthy mammalian brain. In vitro findings were corroborated by PET imaging experiments in NHPs, where [18F]RoSMA-18-d6 uptake in the spleen was dose-dependently attenuated with 1 and 5 mg/kg GW405833, while no specific brain signal was observed. Remarkably, we observed tracer uptake and retention in the NHP spinal cord, which was reduced by GW405833 blockade, pointing toward a potential utility of [18F]RoSMA-18-d6 in probing CB2-expressing cells in the bone marrow. If these observations are substantiated in NHP models of enhanced leukocyte proliferation in the bone marrow, [18F]RoSMA-18-d6 may serve as a valuable marker for hematopoietic activity in various pathologies. In conclusion, [18F]RoSMA-18-d6 proved to be a suitable PET radioligand for imaging CB2 in NHPs, supporting its translation to humans.


Assuntos
Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Animais , Humanos , Compostos Radiofarmacêuticos/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Ligantes , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Primatas/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Radioisótopos de Flúor/metabolismo , Mamíferos/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-37407719

RESUMO

PURPOSE: To assess the reliability of sequential examination under anaesthesia (EUA) to determine pelvic instability and to evaluate radiological and functional outcomes in unstable lateral compression (LC) injuries. METHODS: A prospective case series study was conducted from 2020 to 2022 at a university hospital on 43 cases with LC injuries that met the inclusion criteria. Sequential EUA was carried out in three steps. Posterior-only fixation or anterior-posterior fixation was done according to the algorithm. Each patient was followed up for at least 12 months, both radiologically and functionally. RESULTS: Forty cases proved unstable and were fixed. None showed secondary displacement in the anterior-posterior fixation group. However, five cases (19.2%) of the posterior-only fixation group showed secondary displacement with a mean of 5.9 mm. Four cases of them had tetra-ramic injuries. There is a high tendency for secondary displacement at 14.5 mm or more preoperative displacement of the rami. Patients with secondary displacement showed comparable functional outcome scores to patients without secondary displacement. Posterior-only fixation showed shorter operative time, lesser radiological exposure, blood loss and iatrogenic nerve injury than anterior-posterior fixation. CONCLUSION: EUA is a reliable method to determine pelvic instability and management plan for LC fractures with unilateral anterior ring injury. Anterior-posterior fixation is needed if there is a tetra-ramic fracture or initial anterior ring displacement of 14.5 mm or more, irrespective of EUA.

15.
Res Sq ; 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36747738

RESUMO

GluN2B subunit-containing N-methyl-d-aspartate (NMDA) receptors have been implicated in various neurological disorders. Nonetheless, a validated fluorine-18 labeled positron emission tomography (PET) ligand for GluN2B imaging in the living human brain is currently lacking. As part of our PET ligand development program, we have recently reported on the preclinical evaluation of [18F]OF-NB1 - a GluN2B PET ligand with promising attributes for potential clinical translation. However, the further development of [18F]OF-NB1 is currently precluded by major limitations in the radiolabeling procedure. These limitations include the use of highly corrosive reactants and racemization during the radiosynthesis. As such, the aim of this study was to develop a synthetic approach that allows an enantiomerically pure radiosynthesis of (R)-[18F]OF-NB1 and (S)-[18F]OF-NB1, as well as to assess their in vitro and in vivo performance characteristics for imaging the GluN2B subunit-containing NMDA receptor in rodents. A two-step radiosynthesis involving radiofluorination of the boronic acid pinacol ester, followed by coupling to the 3-benzazepine core structure via reductive amination was employed. The new synthetic approach yielded enantiomerically pure (R)-[18F]OF-NB1 and (S)-[18F]OF-NB1, while concurrently circumventing the use of corrosive reactants. In vitro autoradiograms with mouse and rat brain sections revealed a higher selectivity of (R)-[18F]OF-NB1 over (S)-[18F]OFNB1 for GluN2B-rich brain regions. In concert with these observations, blockade studies with commercially available GluN2B antagonist, CP101606, showed a significant signal reduction, which was more pronounced for (R)-[18F]OF-NB1 than for (S)-[18F]OF-NB1. Conversely, blockade experiments with sigma2 ligand, FA10, did not result in a significant reduction of tracer binding for both enantiomers. PET imaging experiments with CD1 mice revealed a higher brain uptake and retention for (R)-[18F]OF-NB1, as assessed by visual inspection and volumes of distribution from Logan graphical analyses. In vivo blocking experiments with sigma2 ligand, FA10, did not result in a significant reduction of the brain signal for both enantiomers, thus corroborating the selectivity over sigma2 receptors. In conclusion, we have developed a novel synthetic approach that is suitable for upscale to human use and allows the enantiomerically pure radiosynthesis of (R)-[18F]OF-NB1 and (S)-[18F]OF-NB1. While both enantiomers were selective over sigma2 receptors in vitro and in vivo, (R)-[18F]OF-NB1 showed superior GluN2B subunit specificity by in vitro autoradiography and higher volumes of distribution in small animal PET studies.

16.
J Family Community Med ; 30(1): 42-50, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36843865

RESUMO

BACKGROUND: Diabetes-related distress and glycemic control are of a particular concern to primary care physicians because of the impact of the coronavirus disease 2019 pandemic on diabetic patients' lifestyle, psychological well-being and healthcare access. Our aim was to evaluate the relationship between diabetes-related distress and glycemic control in diabetic patients with Type 2 diabetes mellitus (T2DM) in primary care settings during the pandemic. MATERIALS AND METHODS: This cross-sectional study was conducted at primary healthcare clinics in a rural area in Egypt among 430 patients with T2DM during the period from September 2020 to June 2021. All patients were interviewed for their sociodemographic, lifestyle, and clinical characteristics. Diabetes-related distress was measured by the problem areas in the diabetes scale (PAID), where a total score of ≥40 indicated a severe diabetes-related distress. The most recent glycosylated hemoglobin (HbA1c) measurements were used to indicate the glycemic control. Quantile regression model (0.50 quantile) was used to perform the multivariate analysis to identify significant factors associated with HbA1c level. RESULTS: Most of the participants had a suboptimal glycemic control (92.3%), while 13.3% had severe diabetes-related distress. HbA1c level was significantly and positively correlated with the total PAID score and all its sub-domains. Multivariate quantile regression revealed that obesity, multi-morbidity, and severe diabetes-related distress were the only significant determinants of the HbA1c median level. Obese patients had significantly higher median HbA1c compared to patients who were not obese (coefficient = 0.25, P < 0.001). Patients with two or more comorbidities (i.e., multimorbidity) had a significantly higher median HbA1c than patients with single or no chronic comorbidities (coefficient = 0.41, P < 0.001). Severe diabetes-related distress was significantly associated with higher median HbA1c compared to nonsevere diabetes-related distress (coefficient = 0.20, P = 0.018). CONCLUSION: Diabetes-related distress had a significant association with HbA1c level. Family physicians should implement multifaceted programs to optimize diabetes control and reduce any associated distress.

17.
J Nucl Cardiol ; 30(1): 62-73, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35484467

RESUMO

BACKGROUND: Myocardial perfusion imaging by positron emission tomography (PET-MPI) is the current gold standard for quantification of myocardial blood flow. 18F-flurpiridaz was recently introduced as a valid alternative to currently used PET-MPI probes. Nonetheless, optimum scan duration and time interval for image analysis are currently unknown. Further, it is unclear whether rest/stress PET-MPI with 18F-flurpiridaz is feasible in mice. METHODS: Rest/stress PET-MPI was performed with 18F-flurpiridaz (0.6-3.0 MBq) in 27 mice aged 7-8 months. Regadenoson (0.1 µg/g) was used for induction of vasodilator stress. Kinetic modeling was performed using a metabolite-corrected arterial input function. Image-derived myocardial 18F-flurpiridaz uptake was assessed for different time intervals by placing a volume of interest in the left ventricular myocardium. RESULTS: Tracer kinetics were best described by a two-tissue compartment model. K1 ranged from 6.7 to 20.0 mL·cm-3·min-1, while myocardial volumes of distribution (VT) were between 34.6 and 83.6 mL·cm-3. Of note, myocardial 18F-flurpiridaz uptake (%ID/g) was significantly correlated with K1 at rest and following pharmacological vasodilation for all time intervals assessed. However, while Spearman's coefficients (rs) ranged between 0.478 and 0.681, R2 values were generally low. In contrast, an excellent correlation of myocardial 18F-flurpiridaz uptake with VT was obtained, particularly when employing the averaged myocardial uptake from 20 to 40 min post tracer injection (R2 ≥ 0.98). Notably, K1 and VT were similarly sensitive to pharmacological vasodilation induction. Further, mean stress-to-rest ratios of K1, VT, and %ID/g 18F-flurpiridaz were virtually identical, suggesting that %ID/g 18F-flurpiridaz can be used to estimate coronary flow reserve (CFR) in mice. CONCLUSION: Our findings suggest that a simplified assessment of relative myocardial perfusion and CFR, based on image-derived tracer uptake, is feasible with 18F-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents.


Assuntos
Imagem de Perfusão do Miocárdio , Camundongos , Animais , Imagem de Perfusão do Miocárdio/métodos , Estudos de Viabilidade , Tomografia por Emissão de Pósitrons/métodos , Miocárdio , Processamento de Imagem Assistida por Computador
18.
Diabetol Int ; 14(1): 65-75, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35966954

RESUMO

Objective: Egyptian studies in assessing the relationship between diabetes self-care, social support, and glycemic control in primary healthcare (PHC) are limited. Therefore, this study aimed to assess this relationship, and to evaluate the associated factors of diabetes self-care, social support, and glycemic control in Egyptian PHC patients with type 2 diabetes (T2DM). Methods: A cross-sectional study was conducted on 320 T2DM patients at four PHC settings in Port Said city, affiliated with the General Authority of Healthcare. A semi-structured questionnaire was used to collect data, including demographic characteristics, socioeconomic status scale, disease profile, the Arabic versions of the Summary of Diabetes Self-Care Activities, and the received social support scales. Data were collected from January 2020 to June 2020. Results: Diabetes self-care activities, and self-monitoring of blood glucose had a very weak negative correlations with glycated hemoglobin (HbA1c) levels (rho = - 0.125, p = 0.025, rho = - 0.112, p = 0.044, respectively). Receiving social support on following a meal correlated positively and very weakly with HbA1c levels (rho = 0.145, p = 0.010). Hardly positive correlation was found between receiving emotional support on feelings about diabetes, and following a specific diet (rho = 0.169, p = 0.002). Diabetes self-care activities were positively associated with higher education levels, and elevated BMI. Received social support was negatively associated with having coronary artery disease, and marital status e.g. divorced and widow. Increased age, and female gender were the predictors of good glycemic control. Conclusion: Diabetes self-care activities were linked with reduced HBA1c levels. Further studies are needed to evaluate the buffering effect of social support on glycemic outcomes in PHC patients with T2DM.

19.
World J Gastrointest Surg ; 15(12): 2747-2756, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38222004

RESUMO

BACKGROUND: Hajibandeh index (HI), derived from combined levels of C-reactive protein, lactate, neutrophils, lymphocytes and albumin, is a modern predictor of peritoneal contamination and mortality in patients with acute abdominal pathology. AIM: To validate the performance of HI in predicting the presence and nature of peritoneal contamination in patients with acute abdominal pathology in a larger cohort study and to synthesis evidence in a systematic review and meta-analysis. METHODS: The STROBE guidelines and the PRISMA statement standards were followed to conduct a cohort study (ChiCTR2200056183) and a meta-analysis (CRD42022306018), respectively. All adult patients undergoing emergency laparotomy for acute abdominal pathology were eligible. The accuracy of the HI was evaluated using receiver operating characteristic (ROC) curve analysis in the cohort study and using weighted summary area under the curve (AUC) under the fixed and random effects modelling in the meta-analysis. The Quality Assessment of Diagnostic Accuracy Studies 2 criteria were used for methodological quality assessment of the included studies. RESULTS: A total of 1437 patients were included (700 from the cohort study and 737 from the literature search). ROC curve analysis of the cohort study showed that the AUC of HI for presence of contamination, purulent contamination and feculent contamination were 0.79 [95% confidence interval (CI): 0.76-0.82, P < 0.0001], 0.76 (95%CI: 0.72-0.80, P < 0.0001), and 0.83 (95%CI: 0.79-0.86, P < 0.0001), respectively. The meta-analysis showed that the pooled AUC of HI for presence of contamination, purulent contamination and feculent contamination were 0.79 (95%CI: 0.75-0.83), 0.78 (95%CI: 0.74-0.81), and 0.80 (95%CI: 0.77-0.83), respectively. CONCLUSION: The HI is a strong and accurate predictor of intraperitoneal contamination. Although the available evidence is robust, it is limited to the studies conducted by our evidence synthesis group. We encourage other researchers to validate performance of HI in predicting the presence of intraperitoneal contamination and more importantly in predicting mortality following emergency laparotomy.

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