RESUMEN
Background: Several genetic and metabolic variables, most notably the variation in the adipokine gene rs1501298, have been linked to metabolic-associated fatty liver disease etiopathogenesis (MAFLD). Liver biopsy, the gold standard for diagnosing MAFLD, is an invasive procedure; therefore, alternative diagnostic methods are required. Consequently, the integration of these metabolic variables with some of the patients' characteristics may facilitate the development of noninvasive diagnostic methods that aid in the early detection of MAFLD, identification of at-risk individuals and planning of management strategies. Methods: This study included 224 Egyptians (107 healthy individuals and 117 MAFLD patients). Age, sex, BMI, clinical and laboratory characteristics, and rs1501299 adipokine gene polymorphisms were examined. The rs1501299 variant, insulin resistance, hypertension, obesity, blood pressure, lipid profile, hemoglobin A1C level, and hepatic fibrosis predictors were evaluated for MAFLD risk. The feasibility and effectiveness of developing non-invasive MAFLD diagnostic models will be investigated. Results: The +276G/T (rs1501299) polymorphism (GG vs GT/TT) was linked with MAFLD (OR: 0.43, CI: 0.26-0.69, P = 0.002). The GG variants had lower MAFLD rates than those of the GT and TT variants. In addition to altered lipid profiles, patients with MAFLD showed increased gamma-glutamyl transferase levels (GGT: 56 IU/L vs. 36 IU/L). Genetic diversity also affects the accuracy of hepatic fibrosis and steatosis prediction. Hepatic fibrosis and steatosis predictors had receiver operating characteristic (ROC) AUCs of 0.529%, 0.846%, and 0.700-0.825%, respectively. We examined a diagnostic model based on these variables and demonstrated its effectiveness. Conclusion: The Adipokine variant rs1501299 increased the risk of MAFLD. Identifying and genotyping this variation and other metabolic variables allow for a noninvasive diagnostic model for early MAFLD diagnosis and identification of those at risk. This study illuminates the prevention and management of MAFLD. Further research with more participants is needed to verify these models and to prove their MAFLD diagnostic efficacy.
RESUMEN
BACKGROUND: The mechanism of pain control with pulsed radiofrequency (PRF) is unclear. OBJECTIVES: We aimed to compare the efficacy of combined PRF on dorsal root ganglion (DRG) with transforaminal epidural steroid injection (TFESI) vs TFESI-alone on pain improvement and serum tumor necrosis factor-alpha (TNF-a) level in lumbar disc-related radicular pain. STUDY DESIGN: Prospective, randomized, controlled trial. SETTING: Neurology and Pain Management clinics. METHODS: A total of 80 patients with lumbar disc prolapse were divided into 2 groups: combined PRF on DRG with TFESI group and TFESI-alone group. The Numeric Rating Scale (NRS-11), Oswestry Disability Index (ODI), and Functional Rating Index (FRI) before intervention and at 2 weeks, 1 month, and 3 months after the intervention were observed. Serum TNF-a level was assessed pre- and post-intervention at 3 months. RESULTS: The scores of NRS-11, ODI, and FRI showed a significant improvement at 2 weeks, 1 month, and 3 months following intervention in both combined PRF & TFESI group and TFESI-alone group (P < 0.001 in all comparisons), with no significant difference between the 2 groups. Serum TNF-a levels showed a statistically significant reduction, 3 months following intervention in the combined PRF & TFESI group (P < 0.001), but not in the TFESI-alone group (P = 0.297) (P between groups < 0.001). LIMITATIONS: The main limitation of this study is that TNF-a level was not assessed earlier to see how long the steroids might reduce TNF-a. On the other hand, further study with extended follow-up periods is needed to confirm the long-term lowering effect of TNF-a provided by PRF. CONCLUSIONS: Combined PRF on DRG with TFESI showed similar outcomes to TFESI-alone in relieving pain in patients with lumbar disc prolapse. However, PRF on DRG caused a significant decrease in TNF-a serum levels at 3 months.
Asunto(s)
Desplazamiento del Disco Intervertebral , Dolor de la Región Lumbar , Radiculopatía , Humanos , Factor de Necrosis Tumoral alfa/uso terapéutico , Estudios Prospectivos , Ganglios Espinales , Resultado del Tratamiento , Inyecciones Epidurales , Dolor de la Región Lumbar/tratamiento farmacológico , Dolor de la Región Lumbar/patología , Esteroides/uso terapéutico , Desplazamiento del Disco Intervertebral/terapia , Desplazamiento del Disco Intervertebral/tratamiento farmacológico , Prolapso , Radiculopatía/tratamiento farmacológico , Vértebras Lumbares/patologíaRESUMEN
Background and Aims: SARS-CoV-2 infection has been recorded in 230 countries to date. Obesity has a negative impact on one's quality of life and is one of the main causes of mortality globally. Obesity affects the immune system, making the host more susceptible to infectious infections. Also, obesity commonly provokes the severity of respiratory diseases so the correlation of LEP rs7799039 Polymorphism in corpulent patients with COVID-19 infection was clearly investigated in the current study. Methods: A total of 232 patients were recruited, 116 patients were obese with COVID-19 infection, and 116 patients were non obese COVID-19. Fasting blood glucose test (FBG), hemoglobin A1C (HbA1C), complete blood count (CBC), international normalized ratio (INR), urea, alanine transaminase (ALT), aspartate aminotransferase (AST), D dimer and C-reactive protein (CRP) were estimated. C.T. scan was performed for each patient, and C.T. severity score was calculated. Genotyping for the leptin rs7799039 SNPs was performed by TaqMan® (Applied Biosystems Step One TM Real-time PCR). Results: Regarding LEP polymorphism, all individuals of non-obese groups significantly had the homozygous allele GG (100%), whereas only 56% of obese groups had GG alleles (P = 0.001). The severity scores significantly (P = 0.001) varied regarding LEP polymorphism regarding Rs7799039, where the largest proportion of those with Grade IV had the homozygous allele AA (57.1%). Conclusion: There was a correlation between the leptin gene allelic discrimination and COVID-19 CT brutality in obese patients. The A allele was considered a risk factor for severity in COVID-19 patients while the G allele contributes to decreasing that risk.
RESUMEN
(1) Background: Type 2 diabetes mellitus (T2DM) is one of the rapidly growing healthcare problems, and several vitamin D receptor (VDR) polymorphisms seem to modulate the risk of T2DM. Our research was designed to investigate the allelic discrimination of VDR polymorphisms and T2DM occurrence risk. (2) Methods: This case-control research included 156 patients with T2DM and 145 healthy control subjects. Most of the study population were males 56.6% vs. 62.8% in the case and control groups, respectively. Genotyping for VDR single nucleotide polymorphisms (SNPs), rs228570 (Fok1), rs7975232 (Apa1), and rs1544410 (Bsm1) was compared between both groups. (3) Results: There was a negative link between vitamin D levels and insulin sensitivity. A significant difference was noted in the allelic discrimination of VDR polymorphism rs228570 and rs1544410 between the study groups (p < 0.001). No difference was observed in the allelic discrimination of VDR polymorphism rs7975232 between the groups (p = 0.063). Moreover, T2DM patients had significantly higher levels of fasting blood sugar (FBS), glycated hemoglobin HbA1c, 2-h post-prandial blood sugar (PP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), total cholesterol, and triglycerides (p < 0.001), while High-Density Lipoprotein (HDL) Cholesterol (HDL-C) was significantly decreased (p = 0.006). (4) Conclusions: VDR polymorphisms had a positive association with T2DM risk among the Egyptian population. Further large-scale research using deep sequencing of samples is strongly urged to investigate different vitamin D gene variants and interactions, as well as the influence of vitamin D on T2DM.
RESUMEN
INTRODUCTION: Nasal colonization with coagulase-negative staphylococci (CoNS) may be a preliminary risk factor for systemic infection. The aim of this study was to assess the frequency of ica A and D genes and biofilm formation among hospital-acquired nasal colonizing CoNS strains isolated from neonates in the neonatal intensive care units (NICUs). Antibiotic sensitivity patterns and some relevant risk factors were estimated. METHODS: This study assessed nasal colonization with CoNS among neonates at days one and three of admission to NICUs of Beni-Suef University Hospital and Beni-Suef General Hospital from November 2015 to May 2016. The isolates were screened and identified; susceptibility testing was performed. Biofilm formation was examined using the Congo red agar method. Isolates identified as CoNS were tested by polymerase chain reaction (PCR) for the presence of mecA and icaA and icaD genes. RESULTS: A total of 340 nasal swabs were collected from 170 neonates. The incidence of nasal colonization with CoNS was 50%. The species most frequently isolated were S. haemolyticus and S. epidermidis. Multidrug resistance (MDR) was detected in 86% of isolates. It was found that there was a strong association between the presence of mecA gene and phenotypic resistance to methicillin and also the presence of the icaA gene and biofilm formation. CONCLUSIONS: Neonates admitted to NICUs can become reservoirs for CoNS strains, leading to potential dissemination of MDR strains into the community.
RESUMEN
Although it is well established that bulbo-spinal serotonergic projections contribute to pain control mechanisms, whether they exert anti- or pro-nociceptive modulations is still a matter of debate. In order to reappraise the role of 5-HT in descending controls, we used RNA interference to selectively inhibit 5-HT synthesis in B3 neurons and assess resulting changes in nociception. Rats were injected into the bulbar B3 group with a recombinant lentiviral vector, LV-shTPH2, encoding RNA interfering with tryptophan hydroxylase 2 expression. Together with the long term disappearance of this enzyme in the whole rostro-caudal extent of B3 group, 5-HT was markedly depleted selectively in the dorsal horn at all levels of the spinal cord. In contrast, immunolabeling of the 5-HT transporter was unaffected by LV-shTPH2 injection, indicating the preservation of serotonergic fibers integrity. Whereas mechanical and thermal nociceptive thresholds were unchanged by 5-HT depletion, marked reductions in intraplantar formalin (but not carrageenin)-evoked nocifensive responses, and, in contrast, significant increases in mechanical and thermal hyperalgesia evoked by sciatic nerve ligation were noted in LV-shTPH2-injected rats versus controls. Parallel changes in c-Fos immunolabeling within the dorsal horn confirmed that bulbo-spinal serotonergic projections modulate pain signaling under these various conditions. These results suggest that serotonergic neurons of the B3 group are only moderately concerned, if any, by acute nociception but exert modulatory influences under pain sensitizing conditions. The opposite changes in formalin injected- versus sciatic nerve ligated rats might be related to the implication of different receptors in 5-HT-mediated modulation of inflammatory versus neuropathic pain.
Asunto(s)
Inflamación/patología , Vías Nerviosas/metabolismo , Neuralgia/patología , Nocicepción/fisiología , Serotonina/metabolismo , Médula Espinal/patología , Animales , Carragenina/toxicidad , Modelos Animales de Enfermedad , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Inflamación/inducido químicamente , Lentivirus/genética , Lentivirus/metabolismo , Masculino , Neuralgia/complicaciones , Dimensión del Dolor , Umbral del Dolor/efectos de los fármacos , Umbral del Dolor/fisiología , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Interferencia de ARN/fisiología , Ratas , Ratas Sprague-Dawley , Serotonina/genética , Médula Espinal/metabolismo , Transducción Genética , Triptófano Hidroxilasa/genética , Triptófano Hidroxilasa/metabolismoRESUMEN
Granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor, is a standard supportive therapy given during cancer treatment. It induces acceleration in neutrophil recovery through stimulation of mobilization of hematopoietic progenitors. Given that the latter is also induced by chemotherapy itself, the timing of administration of G-CSF postchemotherapy might impact the resultant overall effects. The present study aimed to determine the optimal timing of G-CSF postchemotherapy to exert its optimal effects on the immune cell recovery and its impact on antigen-specific CD8+ T-cell response. B6 mice were treated once with cyclophosphamide (4 mg/mouse; CTX) and then daily with G-CSF (5 g/mouse) from Days 1-5, 2-5 or 5-9 post-CTX treatment. The total numbers of various immune cell types were analyzed on Days 7, 9 and 12 post-CTX treatment. To evaluate effects on CD8+ T-cell response, a pmel-1 transgenic mouse model was used in combination with prime boost peptide vaccination therapy. The total number of white blood cells (WBC), neutrophils, monocytes, lymphocytes, granulocytes and dendritic cells (DC) were significantly increased after G-CSF treatment in particular when G-CSF was administered from Days 2-5 post-CTX treatment. Application of this timing of G-CSF and CTX treatment after adoptive transfer of T-cells followed by prime-boost vaccination with antigenic peptide did not block the expansion of the donor pmel-1 CD8+ T-cells. In conclusion, adjusting the timing of treatment with G-CSF postchemotherapy can optimize its promoting effects on recovery of myeloid cells without altering the associated antigen-specific immunity.