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1.
Res Sq ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38352490

RESUMO

Impairments in somatosensory function are a common and often debilitating consequence of neurological injury, with few effective interventions. Building on success in rehabilitation for motor dysfunction, the delivery of vagus nerve stimulation (VNS) combined with tactile rehabilitation has emerged as a potential approach to enhance recovery of somatosensation. In order to maximize the effectiveness of VNS therapy and promote translation to clinical implementation, we sought to optimize the stimulation paradigm and identify neural mechanisms that underlie VNS-dependent recovery. To do so, we characterized the effect of tactile rehabilitation combined with VNS across a range of stimulation intensities on recovery of somatosensory function in a rat model of chronic sensory loss in the forelimb. Consistent with previous studies in other applications, we find that moderate intensity VNS yields the most effective restoration of somatosensation, and both lower and higher VNS intensities fail to enhance recovery compared to rehabilitation without VNS. We next used the optimized intensity to evaluate the mechanisms that underlie recovery. We find that moderate intensity VNS enhances transcription of Arc, a canonical mediator of synaptic plasticity, in the cortex, and that transcript levels were correlated with the degree of somatosensory recovery. Moreover, we observe that blocking plasticity by depleting acetylcholine in the cortex prevents the VNS-dependent enhancement of somatosensory recovery. Collectively, these findings identify neural mechanisms that subserve VNS-dependent somatosensation recovery and provide a basis for selecting optimal stimulation parameters in order to facilitate translation of this potential intervention.

2.
Immunol Cell Biol ; 102(4): 240-255, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38265162

RESUMO

Therapy-induced senescence (TIS) is a primary response to chemotherapy, contributing to untoward treatment outcomes such as evasion of immunosurveillance. Despite the established role of the complement system in the immune response to cancer, the role of complement in mediating the immune response against senescent tumor cells remains poorly understood. To explore this relationship, we exposed lung adenocarcinoma (A549), breast adenocarcinoma (MCF7) and pancreatic carcinoma (Panc-1) cell lines to sublethal doses of either etoposide or doxorubicin to trigger TIS. Identification of TIS was based on morphological changes, upregulation of the senescence-associated ß-galactosidase, p21Cip1 induction and lamin B1 downregulation. Using immunofluorescence microscopy, quantitative PCR, ELISA of conditioned media and in silico analysis, we investigated complement activation, complement protein expression, C3 levels in the conditioned media of senescent cells and secreted complement proteins as part of the senescence-associated secretory phenotype (SASP), respectively. In cell lines undergoing TIS, complement-related changes included (i) activation of the terminal pathway, evidenced by the deposition of C5b-9 on senescent cells; (ii) an increase in the expression of CD59 and complement factor H and (iii) in A549 cells, an elevation in the expression of C3 with its secretion into the medium. In addition, increased C3 expression was observed in breast cancer samples expressing TIS hallmarks following exposure to neoadjuvant chemotherapy. In conclusion, TIS led to the activation of complement, upregulation of complement regulatory proteins and increased C3 expression. Complement appears to play a role in shaping the cancer microenvironment upon senescence induction.


Assuntos
Doxorrubicina , Neoplasias , Humanos , Meios de Cultivo Condicionados , Doxorrubicina/farmacologia , Linhagem Celular , Fatores de Transcrição , Ativação do Complemento , Proteínas do Sistema Complemento
3.
Cell Biochem Funct ; 42(1): e3897, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38063410

RESUMO

Polycystic ovarian syndrome (PCOS) is an endocrinological disorder aroused due to hormonal disturbances. It is characterized by anovulation due to an excess of androgen and estrogen hormones, thus leading to the formation of multiple cysts, imposing life-threatening conditions. This manuscript aimed to introduce a natural estrogen receptor (ESR) inhibitors that can provide protection against PCOS. The computational analysis of Linum usitatissimum seeds  compounds against ESR alpha receptor was performed, and the binding affinities of the ligand compounds and receptor proteins were scrutinized. Nine lignin compounds were docked, and the results were compared with that of reference estrogen receptor inhibitors, clomiphene, and tamoxifen. The binding affinity scores for pinoresinol, lariciresinol, secoisolariciresinol, and matairesinol were -10.67, -10.66, -10.91, and -10.60 kcal mol-1 , respectively. These were comparable to the binding affinity score of reference compounds -11.406 kcal mol-1 for clomiphene and -10.666 kcal mol-1 for tamoxifen. Prime MM-GBSA studies showcased that Linum usitatissimum seeds compounds exhibit significant efficacy and efficiency towards receptor protein. Moreover, MD-simulation studies were performed and the results depict that the lignin compounds form stable complexes at 300 K throughout the simulation time. For further clarity, in-vitro experiments were carried out. The results exhibit the decline in cell proliferation in a concentration-dependent manner by extract 1 (ethyl acetate) EX1 and extract 2 (petroleum ether) EX2. Hence, providing evidence regarding the anti-estrogenic activity of the sample extracts. Collectively, these results showed that flax seed can reduce the levels of estrogen, which can induce ovulation and prevent cyst formation, and ultimately can provide protection against PCOS.


Assuntos
Linho , Síndrome do Ovário Policístico , Humanos , Feminino , Linho/química , Linho/metabolismo , Receptores de Estrogênio/metabolismo , Síndrome do Ovário Policístico/tratamento farmacológico , Lignina/análise , Lignina/metabolismo , Sementes/química , Clomifeno/análise , Clomifeno/metabolismo , Estrogênios , Tamoxifeno , Extratos Vegetais/farmacologia
4.
Neuroscience ; 532: 79-86, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37778688

RESUMO

Chronic sensory loss is a common and undertreated consequence of many forms of neurological injury. Emerging evidence indicates that vagus nerve stimulation (VNS) delivered during tactile rehabilitation promotes recovery of somatosensation. Here, we systematically varied the timing of VNS relative to tactile rehabilitation to determine the paradigm that yields the greatest degree of somatosensory recovery after peripheral nerve injury (PNI). The medial and ulnar nerves in rats were transected, causing chronic sensory loss. Eight weeks after injury, rats were given a VNS implant followed by four weeks of tactile rehabilitation sessions consisting of repeated mechanical stimuli to the previously denervated forepaw. Rats received VNS before, during, or after tactile rehabilitation. Delivery of VNS during rehabilitative training generates robust, significant recovery compared to rehabilitative training without stimulation (56 ± 14% improvement over sham stimulation). A matched amount of VNS before training, immediately after training, or two hours after training is significantly less effective than VNS during rehabilitative training and fails to improve recovery compared to rehabilitative training alone (5 ± 10%, 4 ± 11%, and -7 ± 22% improvement over sham stimulation, respectively). These findings indicate that concurrent delivery of VNS during rehabilitative training is most effective and illustrate the importance of considering stimulation timing for clinical implementation of VNS therapy.


Assuntos
Traumatismos dos Nervos Periféricos , Estimulação do Nervo Vago , Ratos , Animais , Membro Anterior/fisiologia , Tato , Mãos , Traumatismos dos Nervos Periféricos/terapia , Nervo Vago
5.
Neurorehabil Neural Repair ; 37(9): 652-661, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37694568

RESUMO

BACKGROUND: Chronic sensory loss is a common and undertreated consequence of many forms of neurological injury. Emerging evidence indicates that vagus nerve stimulation (VNS) delivered during tactile rehabilitation promotes recovery of somatosensation. OBJECTIVE: Here, we characterize the amount, intensity, frequency, and duration of VNS therapy paradigms to determine the optimal dosage for VNS-dependent enhancement of recovery in a model of peripheral nerve injury (PNI). METHODS: Rats underwent transection of the medial and ulnar nerves in the forelimb, resulting in chronic sensory loss in the paw. Eight weeks after injury, rats were implanted with a VNS cuff and received tactile rehabilitation sessions consisting of repeated mechanical stimulation of the previously denervated forepaw paired with short bursts of VNS. Rats received VNS therapy in 1 of 6 systematically varied dosing schedules to identify a paradigm that balanced therapy effectiveness with a shorter regimen. RESULTS: Delivering 200 VNS pairings a day 4 days a week for 4 weeks produced the greatest percent improvement in somatosensory function compared to any of the 6 other groups (One Way analysis of variance at the end of therapy, F[4 70] P = .005). CONCLUSIONS: Our findings demonstrate that an effective VNS therapy dosage delivers many stimulations per session, with many sessions per week, over many weeks. These results provide a framework to inform the development of VNS-based therapies for sensory restoration.


Assuntos
Traumatismos dos Nervos Periféricos , Estimulação do Nervo Vago , Animais , Ratos , Membro Anterior , Mãos , Extremidade Superior
6.
Crit Care Res Pract ; 2023: 3775670, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37583653

RESUMO

Background: The utility of the Sequential Organ Failure Assessment (SOFA) score in predicting mortality in the intensive care unit (ICU) has been demonstrated before, but serial testing in various settings is required to validate and improve the score. This study examined the utility of the SOFA score in predicting mortality in Jordanian ICU patients and aimed to find a modified score that required fewer laboratory tests. Methods: A prospective observational study was conducted at Jordan University Hospital (JUH). All adult patients admitted to JUH ICUs between June and December 2020 were included in the study. SOFA scores were measured daily during the whole ICU stay. A modified SOFA score (mSOFA) was constructed from the available laboratory, clinical, and demographic data. The performance of the SOFA, mSOFA, qSOFA, and SIRS in predicting ICU mortality was assessed using the area under the receiver operating characteristic curve (AUROC). Results: 194 patients were followed up. SOFA score (mean ± SD) at admission was significantly higher in non-survivors (7.5 ± 3.9) compared to survivors (2.4 ± 2.2) and performed the best in predicting ICU mortality (AUROC = 0.8756, 95% CI: 0.8117-0.9395) compared to qSOFA (AUROC = 0.746, 95% CI: 0.655-0.836) and SIRS (AUROC = 0.533, 95% CI: 0.425-0.641). The constructed mSOFA included points for the hepatic and CNS SOFA scores, in addition to one point each for the presence of chronic kidney disease or the use of breathing support; it performed as well as the SOFA score in this cohort or better than the SOFA score in a subgroup of patients with heart disease. Conclusion: SOFA score was a good predictor of mortality in a Jordanian ICU population and better than qSOFA, while SIRS could not predict mortality. Furthermore, the proposed mSOFA score which employed fewer laboratory tests could be used after validation from larger studies.

7.
Nutrients ; 15(14)2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37513546

RESUMO

When it comes to reproductive health, various lifestyle habits can act as major contributors to either an optimized or worsened scenario of female and male fertility [...].


Assuntos
Fertilidade , Saúde Reprodutiva , Gravidez , Masculino , Humanos , Feminino , Estado Nutricional , Estilo de Vida
8.
Cureus ; 15(4): e37055, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37143620

RESUMO

The current meta-analysis was conducted to determine the predictors of acute respiratory distress syndrome (ARDS) in patients with sepsis. The present meta-analysis was conducted in accordance with the MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. We conducted a systematic search using the PubMed, Cochrane Library, and EMBASE databases for studies published between 1 January 2000 and 28 February 2023 that assessed the predictors of ARDS in patients with sepsis. We used key terms such as "predictors," "acute respiratory distress syndrome," and "sepsis" to search for relevant articles. Our search was limited to human studies published in English. A total of six studies were included in this meta-analysis. Of the six studies, four were retrospective and two were prospective. The pooled incidence of ARDS was 11.27%. We identified six factors with a consistent and statistically significant association with ARDS, including sequential organ failure assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) II score, pulmonary sepsis, smoking, pancreatitis, and C-reactive protein. Age, diabetes, and chronic obstructive pulmonary disease (COPD) were not found to be significantly associated with ARDS in this patient population. It is important for healthcare providers to consider these predictors when assessing patients with sepsis and septic shock to identify those at high risk for developing ARDS and implement appropriate preventive measures.

9.
Curr Protoc ; 3(3): e721, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36946745

RESUMO

Flow cytometry (FCM) is a state-of-the-art technique for the qualitative and quantitative assessment of cells and other particles' physical and biological properties. These cells are suspended within a high-velocity fluid stream and pass through a laser beam in single file. The main principle of the FCM instrument is the light scattering and fluorescence emission upon the interaction of the fluorescent particle with the laser beam. It also allows for the physical sorting of particles depending on different parameters. A flow cytometer comprises different components, including fluidic, optics, and electronics systems. This article briefly explains the mechanism of all components of a flow cytometer to clarify the FCM technique's general principles, provides some useful guidelines for the proper design of FCM panels, and highlights some general applications and important applications in cancer research. © 2023 Wiley Periodicals LLC.


Assuntos
Neoplasias , Projetos de Pesquisa , Humanos , Citometria de Fluxo/métodos , Corantes
10.
Life Sci ; 314: 121316, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36565814

RESUMO

AIMS: Traumatic brain injury (TBI) constitutes a serious public health concern. Although TBI targets the brain, it can exert several systemic effects which can worsen the complications observed in TBI subjects. Currently, there is no FDA-approved therapy available for its treatment. Thus, there has been an increasing need to understand other factors that could modulate TBI outcomes. Among the factors involved are diet and lifestyle. High-fat diets (HFD), rich in saturated fat, have been associated with adverse effects on brain health. MAIN METHODS: To study this phenomenon, an experimental mouse model of open head injury, induced by the controlled cortical impact was used along with high-fat feeding to evaluate the impact of HFD on brain injury outcomes. Mice were fed HFD for a period of two months where several neurological, behavioral, and molecular outcomes were assessed to investigate the impact on chronic consequences of the injury 30 days post-TBI. KEY FINDINGS: Two months of HFD feeding, together with TBI, led to a notable metabolic, neurological, and behavioral impairment. HFD was associated with increased blood glucose and fat-to-lean ratio. Spatial learning and memory, as well as motor coordination, were all significantly impaired. Notably, HFD aggravated neuroinflammation, oxidative stress, and neurodegeneration. Also, cell proliferation post-TBI was repressed by HFD, which was accompanied by an increased lesion volume. SIGNIFICANCE: Our research indicated that chronic HFD feeding can worsen functional outcomes, predispose to neurodegeneration, and decrease brain recovery post-TBI. This sheds light on the clinical impact of HFD on TBI pathophysiology and rehabilitation as well.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Lesões Encefálicas Traumáticas/complicações , Encéfalo/metabolismo , Lesões Encefálicas/complicações , Camundongos Endogâmicos C57BL
11.
J Adv Res ; 50: 83-105, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36332796

RESUMO

BACKGROUND: Parkinson's disease (PD) is a disease of ⍺-synuclein aggregation-mediated dopaminergic neuronal loss in the substantia nigra pars compacta, which leads to motor and non-motor symptoms. Through the last two decades of research, there has been growing consensus that inflammation-mediated oxidative stress, mitochondrial dysfunction, and cytokine-induced toxicity are mainly involved in neuronal damage and loss associated with PD. However, it remains unclear how these mechanisms relate to sporadic PD, a more common form of PD. Both enteric and central nervous systems have been implicated in the pathogenesis of sporadic PD, thus highlighting the crosstalk between the gut and brain. AIM: of Review: In this review, we summarize how alterations in the gut microbiome can affect PD pathogenesis. We highlight various mechanisms increasing/decreasing the risk of PD development. Based on the previous supporting evidence, we suggest how early interventions could protect against PD development and how controlling specific factors, including our diet, could modify our perspective on disease mechanisms and therapeutics. We explain the strong relationship between the gut microbiota and the brain in PD subjects, by delineating the multiple mechanisms involved inneuroinflammation and oxidative stress. We conclude that the neurodetrimental effects of western diet (WD) and the neuroprotective effects of Mediterranean diets should be further exploredin humans through clinical trials. Key Scientific Concepts of Review: Alterations in the gut microbiome and associated metabolites may contribute to pathogenesis in PD. In some studies, probiotics have been shown to exert anti-oxidative effects in PD via improved mitochondrial dynamics and homeostasis, thus reducing PD-related consequences. However, there is a significant unmet need for randomized clinical trials to investigate the effectiveness of microbial products, probiotic-based supplementation, and dietary intervention in reversing gut microbial dysbiosis in PD.


Assuntos
Microbioma Gastrointestinal , Doença de Parkinson , Probióticos , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Microbioma Gastrointestinal/fisiologia , Inflamação/metabolismo , Probióticos/uso terapêutico , Dieta
12.
J Immunol Res ; 2022: 7263740, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36573216

RESUMO

Background: The ability of vaccine-induced antibodies to bind C1q could affect pathogen neutralization. In this study, we investigated C1q binding and subsequent complement activation by anti-spike (S) protein receptor-binding domain (RBD) specific antibodies produced following vaccination with either the mRNA vaccine BNT162b2 or the inactivated vaccine BBIBP-CorV. Methods: Serum samples were collected in the period of July 2021-March 2022. Participants' demographic data, type of vaccine, date of vaccination, as well as adverse effects of the vaccine were recorded. The serum samples were incubated with S protein RBD-coated plates. Levels of human IgG, IgA, IgM, C1q, and mannose-binding lectin (MBL) that were bound to the plate, as well as formed C3d, and C5b-9 were compared between different groups of participants. Results: A total of 151 samples were collected from vaccinated (n = 116) and nonvaccinated (n = 35) participants. Participants who received either one or two doses of BNT162b2 formed higher levels of anti-RBD IgG and IgA than participants who received BBIBP-CorV. The anti-RBD IgG formed following either vaccine bound C1q, but significantly more C1q binding was observed in participants who received BNT162b2. Subsequently, C5b-9 formation was significantly higher in participants who received BNT162b2, while no significant difference in C5b-9 formation was found between the nonvaccinated and BBIBP-CorV groups. The formation of C5b-9 was strongly correlated to C1q binding and not to MBL binding, additionally, the ratio of formed C5b-9/bound C1q was significantly higher in the BNT162b2 group. Conclusion: Anti-RBD IgG formed following vaccination can bind C1q with subsequent complement activation, and the degree of terminal complement pathway activation differed between vaccines, which could play a role in the protection offered by COVID-19 vaccines. Further investigation into the correlation between vaccine protection and vaccine-induced antibodies' ability to activate complement is required.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Complexo de Ataque à Membrana do Sistema Complemento , Vacina BNT162 , Complemento C1q , COVID-19/prevenção & controle , Proteínas do Sistema Complemento , Vacinação , Anticorpos Antivirais , Imunoglobulina A
13.
Front Public Health ; 10: 1055037, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36478722

RESUMO

Background: Tuberculosis (TB) is one of the leading causes of death from infectious diseases worldwide with numerous undiagnosed and untreated cases, emphasizing the need for TB awareness to minimize transmission and initiate early treatment. Data regarding the knowledge, attitudes, and practices (KAP) toward TB among Jordanians is lacking but requires attention given the massive migration spells to Jordan from neighboring countries in the past decade. Methods: A descriptive cross-sectional study was conducted from May to June 2022. An online questionnaire was developed following World Health Organization (WHO) recommendations for TB KAP surveys and was distributed to Jordanian university students. The questionnaire documented sociodemographic data and measured participants' KAP toward TB. Descriptive and analytic statistics were used to report KAP levels and highlight relevant sociodemographic factors associated with better KAP. Results: 602 participants completed the survey; most were females (60.8%), in their first 3 years of school (84.4%), and from a healthcare field of study (57.0%). The knowledge section median score was 27 out of 51. Knowledge gaps in TB treatment, and to a lesser extent, TB transmission routes were identified. The attitudes section median score was 6 out of 9, attitudes were generally positive toward TB patients with no indication of a social stigma. The practice section median score was 6 out of 8, most participants would take the correct measures if they suspected being infected, yet around 41.0% were not confident that masks are important in preventing airborne diseases. Students in healthcare specialties had significantly better KAP scores and identifying as a smoker was associated with a lower practice score. Conclusion: Although university students displayed satisfactory KAP scores, the focus should be aimed at informing students from non-healthcare fields on TB transmission routes, treatment options, and the role of masks in preventing disease transmission.


Assuntos
Instituições Acadêmicas , Tuberculose , Humanos , Estudos Transversais , Jordânia/epidemiologia , Tuberculose/epidemiologia , Tuberculose/prevenção & controle
14.
Pak J Med Sci ; 38(6): 1639-1643, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35991277

RESUMO

Objective: To evaluate the radiographic patterns on Chest X-Ray (CXR) in accordance with Modified Brixia Scoring as supporting imaging tool in triaging of Corona Virus Disease (COVID-19) pneumonia. Methods: In this cross-sectional study, chest radiographs of suspected COVID patients at emergency triage, Lady Reading Hospital (LRH) from April 18th to July 22nd 2020 were evaluated for patterns of COVID pneumonia and scored in accordance with modified Brixia score. Each zone was categorized as score of "one" for interstitial pattern, "two" for mixed interstitial /alveolar pattern and "three" for alveolar pattern. Radiographic patterns consistent with COVID pneumonia or patients having strong clinical suspicion were advised Polymerase Chain Reaction (PCR) tests. Results: Total of 2,225 individuals were screened for patterns of COVID-19 pneumonia on chest radiograph. Out of these 1465(65.8%) had normal chest radiograph and 760(34.2%) had abnormal findings. Out of the total, 648 suspected COVID patients were selected for PCR. The radiographic patterns ranged from mixed interstitial/alveolar pattern in 261(40.3%) patients, alveolar pattern in 231(35.6%), interstitial pattern in 87(13.4%), pleural effusion in 12(1.9%), other findings in 5(0.8%) while 52(8%) suspected Covid patients had normal radiographs. The PCR was positive in 326(50.3%), negative in 100(15.4%) and inconclusive in 60(9.3%) while 162(25%) were lost to follow up. Amongst the 52 suspected Covid patients having normal chest radiographs, 10 were positive on PCR, 21 negative, seven suspected and two inconclusive, while 12 were lost to follow up. Conclusion: Chest radiograph is used for triaging of suspected COVID pneumonia patients in emergency settings. It assesses the severity of disease according to modified Brixia scoring for treatment plan.

15.
J Immunother Precis Oncol ; 5(1): 13-25, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35663831

RESUMO

The discovery of immune checkpoint inhibitors (ICIs) has revolutionized the care of cancer patients. However, the response to ICI therapy exhibits substantial interindividual variability. Efforts have been directed to identify biomarkers that predict the clinical response to ICIs. In recent years, the gut microbiome has emerged as a critical player that influences the efficacy of immunotherapy. An increasing number of studies have suggested that the baseline composition of a patient's gut microbiota and its dysbiosis are correlated with the outcome of cancer immunotherapy. This review tackles the rapidly growing body of evidence evaluating the relationship between the gut microbiome and the response to ICI therapy. Additionally, this review highlights the impact of antibiotic-induced dysbiosis on ICI efficacy and discusses the possible therapeutic interventions to optimize the gut microbiota composition to augment immunotherapy efficacy.

16.
Nutr Rev ; 80(8): 1927-1941, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35172003

RESUMO

The prevalence of obesity tripled worldwide between 1975 and 2016, and it is projected that half of the US population will be overweight by 2030. The obesity pandemic is attributed, in part, to the increasing consumption of the high-fat, high-carbohydrate Western diet, which predisposes to the development of the metabolic syndrome and correlates with decreased cognitive performance. In contrast, the high-fat, low-carbohydrate ketogenic diet has potential therapeutic roles and has been used to manage intractable seizures since the early 1920s. The brain accounts for 25% of total body glucose metabolism and, as a result, is especially susceptible to changes in the types of nutrients consumed. Here, we discuss the principles of brain metabolism with a focus on the distinct effects of the Western and ketogenic diets on the progression of neurological diseases such as epilepsy, Parkinson's disease, Alzheimer's disease, and traumatic brain injury, highlighting the need to further explore the potential therapeutic effects of the ketogenic diet and the importance of standardizing dietary formulations to assure the reproducibility of clinical trials.


Assuntos
Dieta Cetogênica , Epilepsia , Carboidratos , Humanos , Obesidade , Reprodutibilidade dos Testes
17.
J Inflamm Res ; 15: 153-162, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35046691

RESUMO

BACKGROUND: Complement plays a pivotal role in the immune response to infection. Several studies demonstrated complement activation in sepsis, yet little is known of the relationship of complement terminal pathway activation and the clinical characteristics of sepsis patients. Therefore, we investigated serum C5, soluble C5b-9 (sC5b-9), and soluble CD59 (sCD59) and their relation to organ failure in sepsis patients in the intensive care unit (ICU). METHODS: In this prospective cohort study, all available patients admitted to the adult ICUs between June 2020 and January 2021 were included. Patients were divided into sepsis and non-sepsis groups according to the Sepsis-3 criteria, serum samples from both groups were investigated for the levels of C5, sC5b-9, and sCD59 using commercial sandwich ELISA kits. RESULTS: We analyzed 79 serum samples, 36 were from sepsis patients. We found that sepsis patients had significantly lower C5 (83.6± 28.4 vs 104.4± 32.0 µg/mL, p = 0.004) and higher sCD59 (380.7± 170.5 vs 288.9± 92.5 ng/mL, p = 0.016). sC5b-9, although higher in sepsis patients, did not reach statistical significance (1.5± 0.8 µg/mL vs 1.3± 0.7 µg/mL, p = 0.293). Sepsis patients who died during their ICU stay had significantly higher sCD59 compared to those who survived (437.0 ± 176.7 vs 267.8 ± 79.7 ng/mL, p = 0.003, respectively). Additionally, C5 and sCD59 both correlated to SOFA score in the sepsis group (rs = -0.44, P = 0.007 and = 0.43, P = 0.009, respectively), and a similar correlation was not found in the non-sepsis group. DISCUSSION: In sepsis patients, levels of C5 and sCD59, but not sC5b-9, correlated to the severity of organ damage measured by SOFA. A similar correlation was not found in non-sepsis patients. This indicated that organ damage associated with sepsis led to a more pronounced terminal pathway activation than in non-sepsis patients, it also indicated the potential of using C5 and sCD59 to reflect sepsis severity.

18.
Pak J Med Sci ; 38(1): 62-68, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35035402

RESUMO

BACKGROUND & OBJECTIVES: Pakistan ranked fifth amongst 22 high-burden Tuberculosis countries, and it is an epidemic in Pakistan, hence screening is performed nationally, as part of the ambitious ZERO TB drive. Our objective was to assess the diagnostic accuracy of Computer Aided Detection (CAD4TB) software on chest Xray in screening for pulmonary tuberculosis in comparison with gene-Xpert. METHODS: The study was conducted by Radiology Department Lady Reading Hospital Peshawar in affiliation with Indus Hospital network over a period of one year. Screening was done by using mobile Xray unit equipped with CAD4TB software with scoring system. All of those having score of more than 70 and few selected cases with strong clinical suspicion but score of less than 70 were referred to dedicated TB clinic for Gene-Xpert analysis. RESULTS: Among 26,997 individuals screened, 2617 (9.7%) individuals were found presumptive for pulmonary TB. Sputum samples for Gene-Xpert were obtained in 2100 (80.24%) individuals, out of which 1825 (86.9%) were presumptive for pulmonary TB on CAD4TB only. Gene-Xpert was positive in 159 (8.7%) patients and negative in 1,666(91.3%). Sensitivity and specificity of CAD4TB and symptomatology with threshold score of ≥70 was 83.2% and 12.7% respectively keeping Gene-Xpert as gold standard. CONCLUSION: Combination of chest X-ray analysis by CAD4TB and symptomatology is of immense value to screen a large population at risk in a developing high burden country. It is significantly a more effective tool for screening and early diagnosis of TB in individuals, who would otherwise go undiagnosed.

19.
Catheter Cardiovasc Interv ; 99(2): 234-244, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34797596

RESUMO

BACKGROUND: Long lesions are known to have worse outcomes following percutaneous coronary intervention (PCI), but there are limited data assessing the association between lesion length and clinical outcomes in PCI procedures undertaken in chronic total occlusions (CTO). METHODS AND RESULTS: We formed a longitudinal cohort (2006-2018, n = 27,205) of stable angina patients who underwent PCI to CTO in the British Cardiovascular Intervention Society (BCIS) database. Clinical, demographical, procedural, and outcome data were analyzed in three groups by treated segment length, < 30 mm (n = 11,782), 30-59 mm (n = 10,415), ≥ 60 mm (n = 5008). Prevalence of previous myocardial infarction and PCI were higher in patients in 30-59 mm group or ≥ 60 mm group compared with < 30 mm group. Following multivariable analysis, no significant difference was observed in in-patient death (OR = 30-59 mm group = 1.10, CI:0.55-2.19, p = 0.78) (OR ≥ 60 mm group = 0.82, CI: 0.33-2.05, p = 0.67), and 1-year death (OR = 30-59 mm group = 1.06, CI: 0.81-1.37, p = 0.69) (OR ≥ 60 mm group =1.01, CI: 0.70-1.43, p = 0.99) (< 30 mm group = reference) but in-patient MACE was higher in > = 60 mm group (OR: 1.52, CI: 1.15-2.01, p = 0.06) but similar in 30-59 mm group (OR: 1.16, CI: 0.91-1.48, p = 0.22) compared with < 30 mm group. The adjusted rates of procedural complications were higher in ≥ 60 mm group (OR: 1.61, CI: 1.40-1.85, p < 0.001) but were similar in 30-59 mm group (OR: 1.06, CI: 0.94-1.20, p < 0.31) compared with < 30 mm group. For every 10 mm increase, there was an increased adjusted risk of in-patient procedural complications and coronary perforation but not in-patient MACE or death. CONCLUSION: Patients with very long CTO lesions have higher risk of procedural complications and in-patient MACE but similar risk of short or long-term mortality compared with short CTO lesions.


Assuntos
Oclusão Coronária , Intervenção Coronária Percutânea , Doença Crônica , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/epidemiologia , Oclusão Coronária/terapia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Resultado do Tratamento
20.
Cureus ; 13(7): e16350, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34395130

RESUMO

Purpose This study aimed to assess how healthcare professionals (HCPs) use social media to determine how it influences the quality of patient care. Materials and methods This is a cross-sectional study conducted over eight months, between August 2020 and March 2021 using a questionnaire and checked amongst investigators. Results One hundred fifty-eight participants had electronic devices and 145 (91.9%) used social media at work. 26.6% of these HCPs said they spent less than an hour on social media forums, 31% said they spent one to two hours, 28.5% said two to three hours, and 13.9% said they spent more than four hours. As compared to nurses (46%), consultants and pharmacists use social media at a much lower rate (1% for each group). Compared to junior doctors, a higher percentage of nurses (40%) said they were aware of a social media policy at their hospital (8%). A quarter of healthcare employees (20%) were unaware of their workplace policy, potentially exposing sensitive medical details to the public. More research is needed to assess the particular effects of these results on patient care quality and can help in providing literature informing applications encrypted and secure patient data. Conclusion According to our results, a large percentage of healthcare quality professionals used social media networks. A significant proportion of doctors and nurses use it to visit online medical forums for improving education. A large portion of surveyed sample was unaware of hospital policy on social media usage. Further education is required to improve the right use of social media in the hospital setting.

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