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Cyclopropane fatty acid synthases (CFAS) catalyze the conversion of unsaturated fatty acids to cyclopropane fatty acids (CFAs) within bacterial membranes. This modification alters the biophysical properties of membranes and has been correlated with virulence in several human pathogens. Despite the central role played by CFAS enzymes in regulating bacterial stress responses, the mechanistic properties of the CFAS enzyme family and the consequences of CFA biosynthesis remain largely uncharacterized in most bacteria. We report the first characterization of the CFAS enzyme from Pseudomonas aeruginosa (PA), an opportunistic human pathogen with complex membrane biology that is frequently associated with antimicrobial resistance and high tolerance to various external stressors. We demonstrate that CFAs are produced by a single enzyme in PA and that cfas gene expression is upregulated during the transition to stationary phase and in response to oxidative stress. Analysis of PA lipid extracts reveal a massive increase in CFA production as PA cells enter stationary phase and help define the optimal membrane composition for in vitro assays. The purified PA-CFAS enzyme forms a stable homodimer and preferentially modifies phosphatidylglycerol lipid substrates and membranes with a higher content of unsaturated acyl chains. Bioinformatic analysis across bacterial phyla shows highly divergent amino acid sequences within the lipid-binding domain of CFAS enzymes, perhaps suggesting distinct membrane-binding properties among different orthologs. This work lays an important foundation for further characterization of CFAS in P. aeruginosa and for examining the functional differences between CFAS enzymes from different bacteria.
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Background: To assess the relationship between oocytes with smooth endoplasmic reticulum cluster (SERc) and embryological and birth outcomes in infertile couples. Methods: This was a descriptive study that included 231 infertile patients undergoing in vitro fertilization (IVF) with a total of 2447 mature oocytes (MII), of which 279 oocytes with SERc(+) from 100 patients, the remaining 2168 oocytes with SERc(-). Oocytes were evaluated for the presence or absence of the SERc simultaneously with intracytoplasmic sperm injection at 200x magnification using inverted microscopy - Observe D1. Results: The mean age of patients was 32.05 ± 5.56 years. One hundred patients had at least one SERc(+) oocyte (with 279 SERc(+) and 956 SERc(-) oocytes). One hundred and thirty-one patients had 1212 SERc(-) oocytes. Fertilization outcomes and the rates of good-quality embryos on day 2 and day 5 did not differ between the SERc(+) and the SERc(-) groups. In the first frozen embryo transfer cycles, the clinical pregnancy rate in the group of patients with SERc(+) was not different with the SERc(-) group (61.1% vs 48.78%, p = 0.074, respectively). The live birth rate in the SERc(+) group was statistically significantly higher than the SERc(-) group (57.7% vs 43.9%, p = 0.045, respectively). Conclusion: The fertilization rate, the quality of embryos on days 2 and 5 from oocytes with SERc(+) are similar to those with SERc(-). The live birth rate in the patients with SERc(+) group is statistically significantly higher than the SERc(-) group. There is no difference in clinical pregnancy rate between patients with and without SERc. Therefore, the exclusion of oocytes with SERc should not be recommended.
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BACKGROUND AND PURPOSE: The acute vertebrobasilar occlusion associated with the poor prognosis, particularly tandem occlusion. However, few data on the efficacy of the endovascular therapy was indicated in this occlusion. We investigated whether the additional rescue extracranial vertebral stenting improved clinical outcome by modified Rankin scale (mRS) score within 3 months after the procedure. METHODS: This was a retrospective analysis of patients with acute posterior tandem occlusion who were treated with rescue extracranial vertebral stenting between December 2020 and January 2024 at our hospital. Clinical, neuroimaging, procedural, and complication data were collected. Primary outcomes included the rate of good outcomes (mRS ≤ 2) at 3-month follow-up. RESULTS: Nine patients who underwent rescue extracranial vertebral stenting in posterior circulation tandem occlusions were enrolled in the study. All patients were achieved the successful recanalization (mTICI ≥ 2b). Of Dotter technique in the "distal-to-proximal" approach, Diagnostic-Dotter made up 66.7%. Five patients (55.6%) with good outcome (mRS ≤ 2) at 3 months, and 1 patient (11.1%) underwent suboccipital decompressive craniectomy due to the malignant cerebellar infarction. CONCLUSION: Our study suggests that despite the small series with posterior tandem occlusions, the rescue extracranial vertebral stenting could be an important alternative treatment followed by mechanical thrombectomy.
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Exploring the transformation of carbohydrates into valuable chemicals offers a promising and eco-friendly method for utilizing renewable biomass resources. Developing a bi-functional, sustainable heterogeneous catalyst is of utmost importance to attain a high level of selectivity for the desired product, 2,5-diformylfuran (DFF), in this direct conversion process. In this study, we developed a highly effective catalytic system to convert diverse carbohydrates into DFF. Our approach involved utilizing a MoS2 catalyst supported by amorphous carbon derived from sulfonated sugarcane biomass. The MoS2@SBG-SO3H composite was successfully synthesized using a facile and highly efficient method. The transformation of fructose into DFF achieved a significant yield of 70 % for 5â h at 160 °C using a one-step and one-pot reaction through dehydration and oxidation with oxygen. The oxidation of 5-hydroxymethylfurfural (HMF) into DFF using MoS2@SBG-SO3H was obtained at 94 % DFF within 5â h; the activation energy was 38.3â kJ . mol-1. The catalyst displayed convenient recovery and reusability. The direct synthesis of DFF from various carbohydrates, such as sucrose, glucose, maltose, and lactose, resulted in favorable yields. Our research provides a quick, green, and efficient process for preparing carbon-based solid acid catalysts and DFF.
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Introduction: To explore the feasibility and safety of retroperitoneal laparoscopic partial nephrectomy (RLPN) with selective artery clamp (SAC) in patients with renal cell carcinoma (RCC). Methods: The authors recruited three men and two women who underwent RLPN for T1 RCC between December 2022 and May 2023 at a tertiary hospital. The median age of the patients was 32 years (range, 25-70 years). The tumour size ranged from 3 to 4.5 cm. The R.E.N.A.L scores were 4x, 5p, 8a, 5a, and 8ah. The median preoperative eGFR was 96.9 (74.3-105.2). Renal computed tomography angiography was performed before the surgery to evaluate the artery branches. The operation time, number of clamped arteries, warm ischaemic time (WIT), intraoperative blood loss, RCC type, postoperative hospital stay, changes in renal function, and complications were evaluated. The follow-up duration was 6 months. Results: The median operation time was 120 (75-150) minutes. One artery was clamped in four patients, while three were clamped in one patient. The median WIT was 22 (15-30) min, and the median blood loss was 150 (100-300) ml. No complications were recorded, and the resection margin was negative in all patients. The median decrease in eGFR was 6 (4-30%). Conclusions: RLPN with SAC for T1 RCC is safe and feasible in clinical practice.
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BACKGROUND: Lumbosacral radicular syndrome (LRS) is probably the most frequent neuropathic pain syndrome, exaggerating medical and economy burden on developing countries, such as Vietnam. As a result, the urgence to find an approach which is both affordable and effective always puts great demand on medical researchers. OBJECTIVES: Evaluate the effectiveness of transforaminal pulsed radiofrequency (PRF) stimulation on the dorsal root ganglion (DRG) and epidural steroid injection (ESI) in management of chronic lumbosacral radiculopathy. METHODS: Seventy-six patients with chronic radicular pain were performed transforaminal PRF + ESI by neurosurgeons. Demographic characteristics and surgical outcomes were recorded on admission, pre-procedural and post-procedural for 1-month, 3-month, 6-month and 12-month follow-up. Primary outcome was measured by using Visual Analogue Scale (VAS), Oswestry disability index (ODI) and Straight Leg Raising Test (SLRT). Secondary outcome was subjectively collected based on short assessment of patients' satisfaction (SAPS). RESULTS: Patients who received transforaminal PRF and ESI showed significant improvements on all three evaluation tools (VAS, ODI, SLRT), compared to that before treatment (p<0.001). Pain relief was achievable and long-lasting, which met patients' expectation. No significant complications were observed for 12 months follow-up. CONCLUSION: Transforaminal PRF combined with ESI in management of lumbosacral radiculopathy should be a good method of choice for its effectiveness and safety in management of pain.
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Dolor Crónico , Tratamiento de Radiofrecuencia Pulsada , Radiculopatía , Humanos , Radiculopatía/tratamiento farmacológico , Tratamiento de Radiofrecuencia Pulsada/métodos , Vietnam , Centros de Atención Terciaria , Resultado del Tratamiento , Dolor Crónico/terapia , Dolor Crónico/complicaciones , Esteroides/uso terapéuticoRESUMEN
Rationale: Pseudomonas aeruginosa is the major bacterial pathogen colonizing the airways of adult patients with cystic fibrosis (CF) and causes chronic infections that persist despite antibiotic therapy. Intracellular bacteria may represent an unrecognized reservoir of bacteria that evade the immune system and antibiotic therapy. Although the ability of P. aeruginosa to invade and survive within epithelial cells has been described in vitro in different epithelial cell models, evidence of this intracellular lifestyle in human lung tissues is currently lacking. Objectives: To detect and characterize intracellular P. aeruginosa in CF airway epithelium from human lung explant tissues. Methods: We sampled lung explant tissues from patients with CF undergoing lung transplantation and non-CF lung donor control tissue. We analyzed lung tissue sections for the presence of intracellular P. aeruginosa using quantitative culture and microscopy, in parallel to histopathology and airway morphometry. Measurements and Main Results: P. aeruginosa was isolated from the lungs of seven patients with CF undergoing lung transplantation. Microscopic assessment revealed the presence of intracellular P. aeruginosa within airway epithelial cells in three of the seven patients analyzed at a varying but low frequency. We observed those events occurring in lung regions with high bacterial burden. Conclusions: This is the first study describing the presence of intracellular P. aeruginosa in CF lung tissues. Although intracellular P. aeruginosa in airway epithelial cells is likely relatively rare, our findings highlight the plausible occurrence of this intracellular bacterial reservoir in chronic CF infections.
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Fibrosis Quística , Trasplante de Pulmón , Pulmón , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Mucosa Respiratoria , Humanos , Fibrosis Quística/microbiología , Fibrosis Quística/complicaciones , Femenino , Masculino , Adulto , Mucosa Respiratoria/microbiología , Mucosa Respiratoria/patología , Infecciones por Pseudomonas/microbiología , Pulmón/microbiología , Pulmón/patología , Adulto Joven , Células Epiteliales/microbiologíaRESUMEN
Purpose: The aim of this study was to investigate the correlations between the glycation gap (GG) and renal complications such as urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) in type 2 diabetes mellitus patients. Materials and Methods: A cross-sectional study was conducted on 104 individuals (52 males and 52 females), aged 36-93 years old. Fasting blood glucose (FBG), HbA1c, and serum fructosamine were measured simultaneously. GG was calculated as the difference between the measured and fructosamine-based predicted HbA1c levels (FHbA1c). Results: There was a moderately positive correlation between HbA1c and fructosamine concentration (r = 0.488; p < 0.001). GG was positively correlated with UACR (r = 0.3275; p = 0.0007), negatively correlated with eGFR (r = -0.3400; p = 0.0004). HbA1c was positively correlated with UACR (r = 0.2437; p = 0.0127) but not correlated with eGFR (r = -0.444; p = 0.6542). Fructosamine has a positive correlation with eGFR (r = 0.2426; p = 0.0131) but not with UACR (r = -0.1021; p = 0.3025). Conclusion: GG was positively correlated with UACR and inversely correlated with eGFR in type 2 Diabetes mellitus patients. This suggests that GG is a valuable index for predicting kidney complications due to diabetes.
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Bioactive surface coatings have retained the attention of researchers and physicians due to their versatility and range of applications in orthopedics, particularly in infection prevention. Antibacterial metal nanoparticles (mNPs) are a promising therapeutic, with vast application opportunities on orthopedic implants. The current research aimed to construct a polyelectrolyte multilayer on a highly porous titanium implant using alternating thin film coatings of chitosan and alginate via the layer-by-layer (LbL) self-assembly technique, along with the incorporation of silver nanoparticles (AgNPs) or titanium dioxide nanoparticles (TiO2NPs), for antibacterial and osteoconductive activity. These mNPs were characterized for their physicochemical properties using quartz crystal microgravimetry with a dissipation system, nanoparticle tracking analysis, scanning electron microscopy, and atomic force microscopy. Their cytotoxicity and osteogenic differentiation capabilities were assessed using AlamarBlue and alkaline phosphatase (ALP) activity assays, respectively. The antibiofilm efficacy of the mNPs was tested against Staphylococcus aureus. The LbL polyelectrolyte coating was successfully applied to the porous titanium substrate. A dose-dependent relationship between nanoparticle concentration and ALP as well as antibacterial effects was observed. TiO2NP samples were also less cytotoxic than their AgNP counterparts, although similarly antimicrobial. Together, these data serve as a proof-of-concept for a novel coating approach for orthopedic implants with antimicrobial and osteoconductive properties.
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Objectives: Enhanced recovery after thoracic surgery (ERATS) protocols use a combination of analgesics for pain control and have been associated with decreased opioid requirements. We investigated the impact of continual ERATS refinement on the incidence of opioid-free discharge. Methods: We retrospectively analyzed our prospectively maintained institutional database for elective, opioid-naive robotic thoracoscopic procedures. Demographics, operative outcomes, postoperative opioid dispensed (morphine milligram equivalent), and opioid discharge status were collected. Our primary outcome of interest was factors associated with opioid-free discharge; our secondary objective was to determine the incidence of new persistent opioid users. Results: In total, 466 patients from our optimized ERATS protocol were included; 309 (66%) were discharged without opioids. However, 34 (11%) of patients discharged without opioids required a prescription postdischarge. Conversely, 7 of 157 patients (11%), never filled their opioid prescriptions given at discharge. Factors associated with opioid-free discharges were nonanatomic resections, mediastinal procedures, minimal pain, and lack of opioid usage on the day of discharge. More importantly, 3.2% of opioid-free discharge patients became new persistent opioid users versus 10.8% of patients filling opioid prescriptions after discharges (P = .0013). Finally, only 2.3% of opioid-naive patients of the entire cohort became chronic opioid users; there was no difference in the incidence of chronic use by opioid discharge status. Conclusions: Optimized opioid-sparing ERATS protocols are highly effective in reducing opioid prescription on the day of discharge. We observed a very low rate of new persistent or chronic opioid use in our cohort, further highlighting the role ERATS protocols in combating the opioid epidemic.
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Background: Enhanced recovery after thoracic surgery (ERATS) protocols use a combination of analgesics for pain control. We investigated the effect of non-steroidal analgesic drugs (NSAIDs) on pain control by comparing patient levels and opioid requirements after robotic pulmonary resections. Methods: We retrospectively analyzed our prospectively maintained institutional database for elective, opioid-naïve robotic thoracoscopic pulmonary resections. All patients received postoperative NSAIDs unless contraindicated or at the discretion of the attending surgeons. Our original protocol (ERATS-V1) was modified to optimize opioid-sparing effect without affecting pain control (ERATS-V2). Demographics, operative outcomes, and postoperative opioid dispensed [morphine milligram equivalent (MME)] were collected. Results: A total of 491 patients (147 ERATS-V1; 344 ERATS-V2) were included in this study. There was no difference in patient characteristics or operative outcomes between ERATS cohorts. Protocol optimization was associated with a 2- to 10-fold reduction of postoperative opioid use without compromising pain control. In ERATS-V1 cohort, there was no difference in pain levels and opioid requirements with NSAID usage. In ERATS-V2 cohort, while pain levels were similar, higher in-hospital opioid consumption was observed in no-NSAID subgroup {MME: 20.5 [interquartile range (IQR), 4.8-40.5] vs. 12.0 (IQR, 2.0-32.2), P=0.0096, schedule II: 14.2 (IQR, 3.0-36.4) vs. 6.8 (IQR, 1.4-24.0), P=0.012} as well as total postoperative schedule II opioid requirement [17.8 (IQR, 3.0-43.5) vs. 8.8 (IQR, 1.5-30), P=0.032]. Conclusions: The opioid-sparing effect of NSAIDs was observed only in optimized ERATS patients. Modifications of our pre-existing ERATS was associated with a significant reduction of opioid consumption without affecting pain levels. This revealed the role of NSAIDs in postoperative pain management otherwise masked by excessive opioids use.
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Background and Objective: The management of large mediastinal tumors requires a complex multidisciplinary approach, particularly in the perioperative setting due to increased risk of hemodynamic compromise. The utilization of extracorporeal membrane oxygenation (ECMO) provides a useful adjunct in the surgical management for biopsy and resection of these mediastinal masses. The objective of this article is to review indications and implementation of ECMO in the surgical management of mediastinal disease. Methods: A literature review of the PubMed database was completed evaluating articles discussing 'extracorporeal circulation', 'cardiopulmonary bypass', 'anesthesia', 'mediastinal disease', and 'mediastinal cancer'. These articles were evaluated for contribution to the discussion of indications and implementation of ECMO in the management of these patients. Key Content and Findings: Large mediastinal tumors place patients at risk of hemodynamic collapse on induction of anesthesia due to compression of vascular structures, tracheobronchial tree and creation of V/Q mismatch. Patients may be stratified regarding their risk of perioperative complications by evaluation of postural symptoms, cross sectional imaging findings and pulmonary function tests. Those patients at elevated perioperative risk may benefit from the utilization of ECMO, most commonly veno-arterial (V-A) ECMO. Guidewires or ECMO cannulas may be placed under local anesthesia prior to induction. Those patients with hemodynamic compromise may receive mechanical circulatory support to allow completion of the operation. Conclusions: The use of a multidisciplinary team consisting of surgeons, anesthesiologists, perfusionists and OR team is critical to the success in the use of ECMO in the resection of mediastinal masses. With diligent preparation, these high-risk patients may be optimally managed at the time of resection.
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Background: Computed tomography (CT) is increasingly used for assessing skeletal muscle characteristics. In cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), reduced limb muscle mass predicts poor clinical outcomes. However, the degree to which quantity or quality of respiratory and nonrespiratory muscles is affected by these diseases remains controversial. Methods: Thoracic CT images of 29 CF, 21 COPD and 20 normal spirometry control subjects were analysed to measure indices of muscle quantity (volume or cross-sectional area) and quality (radiodensity) in respiratory (diaphragm, abdominal) and nonrespiratory (pectoralis, lumbar paraspinal) muscles. Multivariable linear regression assessed relationships of CT measurements with body mass index (BMI), forced expiratory volume in 1â s (FEV1) % pred, inflammation and infection biomarkers, nutritional status and CF genotype. Results: Diaphragm volume in CF was significantly higher than in COPD (by 154%) or controls (by 140%). Abdominal muscle area in CF was also greater than in COPD (by 130%). Nonrespiratory muscles in COPD had more low radiodensity muscle (marker of lipid content) compared to CF and controls. In CF but not COPD, higher BMI and FEV1 % pred were independently associated with higher diaphragm and/or abdominal muscle quantity indices. Serum creatinine also predicted respiratory and nonrespiratory muscle quantity in CF, whereas other biomarkers including genotype correlated poorly with muscle CT parameters. Conclusions: Our data suggest that the CF diaphragm undergoes hypertrophic remodelling, whereas in COPD the nonrespiratory muscles show altered muscle quality consistent with greater lipid content. Thoracic CT can thus identify distinctive respiratory and nonrespiratory muscle remodelling signatures associated with different chronic lung diseases.
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Background and Objective: Bronchogenic cysts represent a rare form of cystic malformation of the respiratory tract. Primarily located in the mediastinum if occurring early in gestation as opposed to the thoracic cavity if arising later in development. However, they can arise from any site along the foregut. They exhibit a variety of clinical and radiologic presentations, representing a diagnostic challenge, especially in areas with endemic hydatid disease. Endoscopic drainage has emerged as a diagnostic and potentially therapeutic option but has been complicated by reports of infection. Surgical excision remains the standard of care allowing for symptomatic resolution and definitive diagnosis via pathologic examination; minimally invasive approaches such as robotic and thoracoscopic approaches aiding treatment. Following complete resection, prognosis is excellent with essentially no recurrence. Methods: A review of the available electronic literature was performed from 1975 through 2022, using PubMed and Google Scholar, with an emphasis on more recent series. We included all retrospective series and case reports. A single author identified the studies, and all authors reviewed the selection until there was a consensus on which studies to include. Key Content and Findings: The literature consisted of relatively small series, mixed between adult and pediatric patients, and the consensus remains that all symptomatic lesions should be excised via minimally invasive approach where feasible. Conclusions: Surgical excision of symptomatic bronchogenic cysts remains the gold standard, with endoscopic drainage being reserved for diagnosis or as a temporizing measure in clinically unstable patients.
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Coronavirus disease 2019 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); it has recently been associated with several hematologic disorders. A 4-year-old boy who had SARS-CoV-2 10 months prior was admitted to the emergency department of our hospital with seizures. His SARS-CoV-2 IgG II level was 885.7 AU/mL. Neuroimaging with cranial computed tomography after admission showed abnormal images of the venous sinus, but this was not sufficient to diagnose cerebral venous sinus thrombosis. Therefore, magnetic resonance imaging and digital subtraction angiography were conducted, which confirmed the diagnosis. He was treated with thrombectomy and anticoagulation drugs, and the clinical outcomes were satisfactory. Because our patient had a medical history of SARS-CoV-2 and exhibited no other risk factors, we present this case as evidence of a potential association between cerebral venous sinus thrombosis and SARS-CoV-2.
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To derive the maturation of neurophysiological processes from childhood to adulthood reflected by the change of motor-evoked potential (MEP) features. 38 participants were recruited from four groups (age mean in years [SD in months], number (males)): children (7.3 [4.2], 7(4)), preadolescents (10.3 [6.9], 10(5)), adolescents (15.3 [9.8], 11(5)), and adults (26.9 [46.2], 10(5)). The navigated transcranial magnetic stimulation was performed on both hemispheres at seven stimulation intensity (SI) levels from sub- to supra-threshold and targeted to the representative cortical area of abductor pollicis brevis muscle. MEPs were measured from three hand- and two forearm-muscles. The input-output (I/O) curves of MEP features across age groups were constructed using linear mixed-effect models. Age and SI significantly affected MEP features, whereas the stimulated side had a minor impact. MEP size and duration increased from childhood to adulthood. MEP onset- and peak-latency dropped in adolescence, particularly in hand muscles. Children had the smallest MEPs with the highest polyphasia, whereas I/O curves were similar among preadolescents, adolescents, and adults. This study illustrates some of the changing patterns of MEP features across the ages, suggesting developing patterns of neurophysiological processes activated by TMS, and to motivate studies with larger sample size.
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Encéfalo , Potenciales Evocados Motores , Estimulación Magnética Transcraneal , Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Modelos Lineales , Encéfalo/crecimiento & desarrolloRESUMEN
Deployment of nucleic acid amplification assays for diagnosing pathogens in point-of-care settings is a challenge due to lengthy preparatory steps. We present a molecular diagnostic platform that integrates a fabless plasmonic nano-surface into an autonomous microfluidic cartridge. The plasmonic 'hot' electron injection in confined space yields a ninefold kinetic acceleration of RNA/DNA amplification at single nucleotide resolution by one-step isothermal loop-mediated and rolling circle amplification reactions. Sequential flow actuation with nanoplasmonic accelerated microfluidic colorimetry and in conjugation with machine learning-assisted analysis (using our 'QolorEX' device) offers an automated diagnostic platform for multiplexed amplification. The versatility of QolorEX is demonstrated by detecting respiratory viruses: SARS-CoV-2 and its variants at the single nucleotide polymorphism level, H1N1 influenza A, and bacteria. For COVID-19 saliva samples, with an accuracy of 95% on par with quantitative polymerase chain reaction and a sample-to-answer time of 13 minutes, QolorEX is expected to advance the monitoring and rapid diagnosis of pathogens.
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COVID-19 , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Ácidos Nucleicos , Humanos , Microfluídica , Colorimetría , Subtipo H1N1 del Virus de la Influenza A/genética , COVID-19/diagnóstico , SARS-CoV-2/genética , Técnicas de Diagnóstico Molecular , ARN Viral/genética , Sensibilidad y EspecificidadRESUMEN
Top-of-the-basilar artery occlusion frequently causes infarction of the midbrain, thalamus, and portions of the temporal and occipital lobes as the vascular supply of these regions comes from the posterior communicating and posterior cerebral arterial tributaries of the basilar artery. Clinical signs include an array of visual, oculomotor, and behavioral abnormalities, usually without prominent motor dysfunction, which makes diagnosis challenging for those inexperienced with these sign. We describe a 59-year-old male presenting with acute ischemic stroke due to top-of-the-basilar artery occlusion. Despite attempting several paraclinical examinations relating the sudden coma with Glasgow Coma Scale of 6 points, the neuroimaging detected the large vessel occlusion that was difficult to recognize. After confirming top-of-the-basilar artery occlusion, the recanalization was realized immediately. The patient was discharged with good clinical recovery.
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The severity and progression of lung disease are highly variable across individuals with cystic fibrosis (CF) and are imperfectly predicted by mutations in the human gene CFTR, lung microbiome variation or other clinical factors. The opportunistic pathogen Pseudomonas aeruginosa (Pa) dominates airway infections in most CF adults. Here we hypothesized that within-host genetic variation of Pa populations would be associated with lung disease severity. To quantify Pa genetic variation within CF sputum samples, we used deep amplicon sequencing (AmpliSeq) of 209 Pa genes previously associated with pathogenesis or adaptation to the CF lung. We trained machine learning models using Pa single nucleotide variants (SNVs), microbiome diversity data and clinical factors to classify lung disease severity at the time of sputum sampling, and to predict lung function decline after 5 years in a cohort of 54 adult CF patients with chronic Pa infection. Models using Pa SNVs alone classified lung disease severity with good sensitivity and specificity (area under the receiver operating characteristic curve: AUROC=0.87). Models were less predictive of lung function decline after 5 years (AUROC=0.74) but still significantly better than random. The addition of clinical data, but not sputum microbiome diversity data, yielded only modest improvements in classifying baseline lung function (AUROC=0.92) and predicting lung function decline (AUROC=0.79), suggesting that Pa AmpliSeq data account for most of the predictive value. Our work provides a proof of principle that Pa genetic variation in sputum tracks lung disease severity, moderately predicts lung function decline and could serve as a disease biomarker among CF patients with chronic Pa infections.