Reliable differentiation of necrosis and active metabolically contours of glioblastoma multiforme using susceptibility-based imaging.

Purpose: Gadolinium-enhancing necrosis in glioblastoma multiforme (GBM), as an occasionally occurring false positive in contrast enhancement (CE) imaging, leads to trouble for segmentation of GBM and treatment. Therefore, the investigation of complementary detection way to identify the metabolically active volume of the tumor with high reliability is very worth to be addressed. Here, we reported on a case of GBM with gadolinium-enhancing necrosis in an experimental CE imaging study in mice and evaluated the discrimination of the necrosis and metabolically active parts of the GBM using conventional and state-of-the-art susceptibility-based MRI. Methods: In this study, following 5-aminolevulinic acid (ALA) and iron supplements (FAC, 6 h after ALA, intra-tumoral injection) to animal, T2*-W imaging and quantitative susceptibility mapping (QSM) were performed, and compared with CE imaging. Results: The signal intensity (SI) of the active and necrosis areas of the case in the CE image demonstrated no significant difference while the SI on the T2*-W images and susceptibility value in QSM changed 24 and 150%, respectively. Conclusion: The preclinical case report provides valuable insights into the potential of susceptibility-based MRI using ALA + FAC to apply as a robust discriminator between necrotic and viable tumors.

Circulating micronutrient levels and their association with sepsis susceptibility and severity: a Mendelian randomization study.

Background: Sepsis, a global health challenge, necessitates a nuanced understanding of modifiable factors for effective prevention and intervention. The role of trace micronutrients in sepsis pathogenesis remains unclear, and their potential connection, especially with genetic influences, warrants exploration. Methods: We employed Mendelian randomization (MR) analyses to assess the causal relationship between genetically predicted blood levels of nine micronutrients (calcium, ß-carotene, iron, magnesium, phosphorus, vitamin C, vitamin B6, vitamin D, and zinc) and sepsis susceptibility, severity, and subtypes. The instrumental variables for circulating micronutrients were derived from nine published genome-wide association studies (GWAS). In the primary MR analysis, we utilized summary statistics for sepsis from two independent databases (UK Biobank and FinnGen consortium), for initial and replication analyses. Subsequently, a meta-analysis was conducted to merge the results. In secondary MR analyses, we assessed the causal effects of micronutrients on five sepsis-related outcomes (severe sepsis, sepsis-related death within 28 days, severe sepsis-related death within 28 days, streptococcal septicaemia, and puerperal sepsis), incorporating multiple sensitivity analyses and multivariable MR to address potential heterogeneity and pleiotropy. Results: The study revealed a significant causal link between genetically forecasted zinc levels and reduced risk of severe sepsis-related death within 28 days (odds ratio [OR] = 0.450; 95% confidence interval [CI]: 0.263, 0.770; p = 3.58 × 10-3). Additionally, suggestive associations were found for iron (increased risk of sepsis), ß-carotene (reduced risk of sepsis death) and vitamin C (decreased risk of puerperal sepsis). No significant connections were observed for other micronutrients. Conclusion: Our study highlighted that zinc may emerges as a potential protective factor against severe sepsis-related death within 28 days, providing theoretical support for supplementing zinc in high-risk critically ill sepsis patients. In the future, larger-scale data are needed to validate our findings.

Computational Fractal-Based Analysis of MR Susceptibility-Weighted Imaging (SWI) in Neuro-Oncology and Neurotraumatology.

Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) technique able to depict the magnetic susceptibility produced by different substances, such as deoxyhemoglobin, calcium, and iron. The main application of SWI in clinical neuroimaging is detecting microbleedings and venous vasculature. Quantitative analyses of SWI have been developed over the last few years, aimed to offer new parameters, which could be used as neuroimaging biomarkers. Each technique has shown pros and cons, but no gold standard exists yet. The fractal dimension (FD) has been investigated as a novel potential objective parameter for monitoring intratumoral space-filling properties of SWI patterns. We showed that SWI patterns found in different tumors or different glioma grades can be represented by a gradient in the fractal dimension, thereby enabling each tumor to be assigned a specific SWI fingerprint. Such results were especially relevant in the differentiation of low-grade versus high-grade gliomas, as well as from high-grade gliomas versus lymphomas.Therefore, FD has been suggested as a potential image biomarker to analyze intrinsic neoplastic architecture in order to improve the differential diagnosis within clinical neuroimaging, determine appropriate therapy, and improve outcome in patients.These promising preliminary findings could be extended into the field of neurotraumatology, by means of the application of computational fractal-based analysis for the qualitative and quantitative imaging of microbleedings in traumatic brain injury patients. In consideration of some evidences showing that SWI signals are correlated with trauma clinical severity, FD might offer some objective prognostic biomarkers.In conclusion, fractal-based morphometrics of SWI could be further investigated to be used in a complementary way with other techniques, in order to form a holistic understanding of the temporal evolution of brain tumors and follow-up response to treatment, with several further applications in other fields, such as neurotraumatology and cerebrovascular neurosurgery as well.

Long-term di-(2-ethylhexyl) phthalate exposure reduces sorafenib treatment efficacy by enhancing mesenchymal transition in hepatocellular carcinoma.

Di(2-ethylhexyl) phthalate (DEHP) is a worldwide common plasticizer. Nevertheless, DEHP is easily leached out to the environment due to the lack of covalent bonds with plastic. High dose of DEHP exposure is often observed in hemodialysis patients because of the continual usage of plastic medical devices. Although the liver is the major organ that catabolizes DEHP, the impact of long-term DEHP exposure on the sensitivity of liver cancer to chemotherapy remains unclear. In this study, we established long-term DEHP-exposed hepatocellular carcinoma (HCC) cells and two NOD/SCID mice models to investigate the effects and the underlying mechanisms of long-term DEHP exposure on chemosensitivity of HCC. The results showed long-term DEHP exposure potentially increased epithelial-mesenchymal transition (EMT) in HCC cells. Next generation sequencing showed that long-term DEHP exposure increased cell adhesion/migratory related genes expression and blunted sorafenib treatment induced genes alterations. Long-term exposure to DEHP reduced the sensitivity of HCC cells to sorafenib-induced anti-migratory effect by enhancing the EMT transcription factors (slug, twist, and ZEB1) and mesenchymal protein (vimentin) expression. In NOD/SCID mice model, we showed that long-term DEHP-exposed HCC cells exhibited higher growth rate. Regarding the anti-HCC effects of sorafenib, subcutaneous HuH7 tumor grew slowly in sorafenib-treated mice. Nonetheless, the anti-tumor growth effect of sorafenib was not observed in long-term DEHP-exposed mice. Higher mesenchymal markers and proliferating cell nuclear antigen (PCNA) expression were found in sorafenib-treated long-term DEHP-exposed mice. In conclusion, long-term DEHP exposure promoted migratory activity in HCC cells and decreased sorafenib sensitivity in tumor-bearing mice.

Comparison of dynamic susceptibility contrast (DSC) using gadolinium and iron-based contrast agents in high-grade glioma at high-field MRI.

PURPOSE: To compare DSC-MRI using Gadolinium (GBCA) and Ferumoxytol (FBCA) in high-grade glioma at 3T and 7T MRI field strengths. We hypothesized that using FBCA at 7T would enhance the performance of DSC, as measured by contrast-to-noise ratio (CNR). METHODS: Ten patients (13 lesions) were assigned to 3T (6 patients, 6 lesions) or 7T (4 patients, 7 lesions). All lesions received 0.1 mmol/kg of GBCA on day 1. Ten lesions (4 at 3T and 6 at 7T) received a lower dose (0.6 mg/kg) of FBCA, followed by a higher dose (1.0-1.2 mg/kg), while 3 lesions (2 at 3T and 1 at 7T) received only a higher dose on Day 2. CBV maps with leakage correction for GBCA but not for FBCA were generated. The CNR and normalized CBV (nCBV) were analyzed on enhancing and non-enhancing high T2W lesions. RESULTS: Regardless of FBCA dose, GBCA showed higher CNR than FBCA at 7T, which was significant for high-dose FBCA (p < .05). Comparable CNR between GBCA and high-dose FBCA was observed at 3T. There was a trend toward higher CNR for FBCA at 3T than 7T. GBCA also showed nCBV twice that of FBCA at both MRI field strengths with significance at 7T. CONCLUSION: GBCA demonstrated higher image conspicuity, as measured by CNR, than FBCA on 7T. The stronger T2* weighting realized with higher magnetic field strength, combined with FBCA, likely results in more signal loss rather than enhanced performance on DSC. However, at clinical 3T, both GBCA and FBCA, particularly a dosage of 1.0-1.2 mg/kg (optimal for perfusion imaging), yielded comparable CNR.

Deep vein diameters and perivascular space scores are associated with deep medullary vein hypo-visibility in patients with white matter hyperintensity.

Background: Deep medullary vein (DMV) hypo-visibility is correlated with white matter hyperintensity (WMH), but the underlying causes remain unclear. This study aimed to explore the relationship between deep vein diameters and perivascular space (PVS) scores, and DMV hypo-visibility in the presence of WMH. Methods: This cross-sectional study prospectively analyzed the clinical and imaging data of 190 cerebral small vessel disease patients with WMH and 40 healthy controls from the Lishui Hospital of Traditional Chinese Medicine affiliated with Zhejiang Chinese Medical University. PVS scores ranging from 0 to 4 were determined according to the PVS counts in the basal ganglia area on T2-weighted magnetic resonance images; high-grade PVS was defined as a PVS score >1. The diameters of the deep cerebral veins, including the bilateral septal veins (SVs), thalamostriate veins (TSVs), lateral ventricular veins (LVVs), and internal cerebral veins, were measured using susceptibility weighted imaging (SWI). Left and right DMV scores, ranging from 0 to 9, were calculated based on the visibility of the DMV on SWI in the ipsilateral frontal, parietal, and occipital lobes. Results: The deep cerebral vein diameters, left and right DMV scores, and high-grade PVS differed between the healthy controls and WMH patients (P<0.05). Left DMV scores were independently associated with age {ß [95% confidence interval (CI)]: 0.050 (0.018, 0.082)}, high-grade PVS [ß (95% CI): 0.998 (0.262, 1.737)], and the diameters of the ipsilateral SVs [ß (95% CI): -1.114 (-1.754, -0.475)], SVs [ß (95% CI): -0.734 (-1.191, -0.277)], and LVVs [ß (95% CI): -0.921 (-1.567, -0.275)] [all false discovery rate (FDR)-corrected P<0.05]. Right DMV scores were independently associated with age [ß (95% CI): 0.071 (0.037, 0.105)], high-grade PVS [ß (95% CI): 0.873 (0.111, 1.635)], and the diameters of the ipsilateral SVs [ß (95% CI): -0.837 (-1.386, -0.289)], TSVs [ß (95% CI): -0.875 (-1.331, -0.419)], and LVVs [ß (95% CI): -1.813 (-2.484, -1.142)] (all FDR-corrected P<0.05). Conclusions: Decreased hypo-visibility of DMVs on SWI was associated with a higher age, the presence of high-grade PVS, and smaller diameters of the ipsilateral deep cerebral veins in individuals with WMH. Our findings provide novel insights into the probable mechanisms leading to high DMV scores.

Antimicrobial activity of spiculisporic acid isolated from endophytic fungus Aspergillus cejpii of Hedera helix against MRSA.

The surge in multidrug-resistant pathogens worldwide has jeopardized the clinical efficiency of many current antibiotics. This problem steered many researchers in their quest to discover new effective antimicrobial agents from natural origins including plants or their residing endophytes. In this work, we aimed to identify the endophytic fungi derived from Hedera helix L. and investigate their potential antimicrobial activity. Bioguided fractionation approach was conducted to isolate the pure compounds from the most active fungal fraction. Out of a total of six different isolated endophytic fungal strains, only Aspergillus cejpii showed the highest activity against all tested microbial strains. The most active fraction was the dichloromethane/methanol fraction (DCM:MeOH), where it showed significant activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Serratia marcescens, Acinetobacter baumannii, Salmonella typhi, and three drug-resistant clinical isolate strains including Methicillin-resistant Staphylococcus aureus (MRSA, H1), Pseudomonas aeruginosa (PS 16), and Acinetobacter baumannii (ACT 322) using tetracyline and kanamycin as the control antibiotics. Bioguided fractionation of the active fraction led to the isolation of the γ-butenolide, spiculisporic acid. Structure elucidation was carried out using 1H and 13C-NMR spectroscopic analysis. The compound showed good antimicrobial activities with minimum inhibitory concentration (MIC) values ranging from 3.9 to 31.25 µg/mL against all tested strains. Gas chromatography coupled to mass spectrometry (GC-MS) profiling was also carried out to identify the metabolites in the microbial crude extract. In conclusion, endophytic fungi, Aspergillus cejpii, isolated from Hedera helix L. roots showed promising antimicrobial activity which merits further in-depth investigations for potential utilization as a source of new antibiotics in the future. It can also be considered as a novel source for spiculisporic acid.

[Does a rapid antibiotic susceptibility test optimize antibiotic therapy of patients with bacteremia ?] / Un antibiogramme rapide optimise-t-il la prise en charge thérapeutique des patients présentant une bactériémie ?

BACKGROUND: We evaluated the contribution of a rapid antibiotic susceptibility test performed directly from a positive blood culture (PBC), the dRAST™, in the management of patients with bacteremia. METHODS: We retrospectively compared the time from sampling to availability of antibiotic susceptibility test (AST) results («time-to-result¼, TTR) between dRAST™ and classic AST (Vitek®2), in 150 patients with bacteremia. The antibiotic treatment of these 150 patients was classified into three categories (optimal, suboptimal, ineffective) according to the time of availability of AST results. RESULTS: Adaptation of antibiotic treatment to optimal therapy following AST results occurred in 46/100 (46 %) of Gram-negative PBC and in 4/50 (2 %) of Gram-positive HP. TTR was significantly lower with dRAST™ compared with classic AST (29:35 (± 08:48) hours versus 50:55 (± 12:45) hours, p < 0.001). CONCLUSION: For patients with bacteremia requiring adjustment of empirical antibiotic therapy based on AST, dRAST™ could allow a faster administration of optimal therapy.

CONTEXTE: Nous avons évalué la contribution d'un antibiogramme rapide réalisé directement à partir d'une hémoculture positive (HP), le dRAST™, dans la prise en charge des patients présentant une bactériémie. Méthodes: Nous avons comparé, rétrospectivement, le délai entre le prélèvement et la disponibilité des résultats d'antibiogramme («temps-pour-résultats¼, TPR) entre le dRAST™ et l'antibiogramme classique (Vitek®2), auprès de 150 patients présentant une bactériémie. Les antibiothérapies de ces 150 patients ont été classés en trois catégories (optimale, suboptimale, inefficace) en fonction du moment d'obtention des résultats de l'antibiogramme. Résultats : L'adaptation du traitement antibiotique en thérapie optimale suite au résultat de l'antibiogramme est survenue chez 46/100 (46 %) des HP à Gram négatif et chez 4/50 (2 %) des HP à Gram positif. Le TPR était significativement plus faible avec le dRAST™ par rapport à l'antibiogramme classique (29:35 (± 08:48) heures versus 50:55 (± 12:45) heures, p < 0,001). CONCLUSION: Pour les patients avec bactériémie nécessitant une adaptation de l'antibiothérapie empirique basée sur l'antibiogramme, le dRAST™ permettrait une administration plus rapide du traitement optimal.

MHC-DRB alleles with amino acids Val11, Phe13, and the shared epitopes promote collagen-induced arthritis and a rapid IgG1 response in Filipino cynomolgus macaques.

Macaques are useful animal models for studying the pathogenesis of rheumatoid arthritis (RA) and the development of anti-rheumatic drugs. The purpose of this study was to identify the major histocompatibility complex (MHC) polymorphisms associated with the pathology of collagen-induced arthritis (CIA) and anti-collagen IgG induction in a cynomolgus macaque model, as MHC polymorphisms affect the onset of CIA in other animal models. Nine female Filipino cynomolgus macaques were immunized with bovine type II collagen (b-CII) to induce CIA, which was diagnosed clinically by scoring the symptoms of joint swelling over 9 weeks. MHC polymorphisms and anti-b-CII antibody titers were compared between symptomatic and asymptomatic macaques. Four of 9 (44%) macaques were defined as the CIA-affected group. Anti-b-CII IgG in the affected group increased in titer approximately 3 weeks earlier compared with the asymptomatic group. The mean plasma IgG1 titer in the CIA-affected group was significantly higher (p < 0.05) than that of the asymptomatic group. Furthermore, the cynomolgus macaque MHC (Mafa)-DRB1*10:05 or Mafa-DRB1*10:07 alleles, which contain the well-documented RA-susceptibility five amino acid sequence known as the shared epitope (SE) in positions 70 to 74, with valine at position 11 (Val11, V11) and phenylalanine at position 13 (Phe13, F13), were detected in the affected group. In contrast, no MHC polymorphisms specific to the asymptomatic group were identified. In conclusion, the presence of V11 and F13 along with SE in the MHC-DRB1 alleles seems essential for the production of IgG1 and the rapid induction of severe CIA in female Filipino cynomolgus macaques.

Iron supplementation in the diets of hybrid catfish (Ictalurus punctatus × I. furcatus) juveniles affected haematocrit levels and potentially decreased disease resistance to Edwardsiella ictaluri.

To prevent catfish idiopathic anaemia, diets fortified with iron have been adopted as a regular practice on commercial catfish farms to promote erythropoiesis. However, the effects of prolonged exposure of excess dietary iron on production performance and disease resistance for hybrid catfish (Ictalurus punctatus × I. furcatus) remains unknown. Four experimental diets were supplemented with ferrous monosulphate to provide 0, 500, 1000, and 1500 mg of iron per kg of diet. Groups of 16 hybrid catfish juveniles (~22.4 g) were stocked in each of 20, 110-L aquaria (n = 5), and experimental diets were offered to the fish to apparent satiation for 12 weeks. At the end of the study, production performance, survival, condition indices, as well as protein and iron retention were unaffected by the dietary treatments. Blood haematocrit and the iron concentration in the whole-body presented a linear increase with the increasing the dietary iron. The remaining fish from the feeding trial was challenged with Edwardsiella ictaluri. Mortality was mainly observed for the dietary groups treated with iron supplemented diets. The results for this study suggest that iron supplementation beyond the required levels does affect the blood production, and it may increase their susceptibility to E. ictaluri infection.

Long-term ambient ozone, omega-3 fatty acid, genetic susceptibility, and risk of mental disorders among middle-aged and older adults in UK biobank.

BACKGROUND: Evidence linking ozone to depression and anxiety disorders remains sparse and results are heterogeneous. It remains unknown whether omega-3 fatty acid, or genetic susceptibility of mental disorders modify the impacts of ozone. The aim is to assess the associations of ambient ozone with depression and anxiety, and further explore the potential modification effects of omega-3 fatty acid and genetic susceptibility. METHODS: In total of 257,534 participants were enrolled from 2006 to 2010 and followed up to 2016. Depression and anxiety were assessed using mental health questionnaires, primary care records and hospital admission records. The annual average concentrations of ozone were calculated and linked to individuals by home address. Dietary intake and plasma concentration were selected to reflect levels of omega-3 fatty acid. Polygenetic risk scores were selected to reflect genetic susceptibility. We examined the associations of ozone and incident mental disorders, and potential modification of omega-3 fatty acid and genetic susceptibility. RESULTS: Incidences of depression (N = 6957) and anxiety (N = 6944) was associated with increase of ozone. Higher levels of omega-3 fatty acid might attenuate the ozone related depression risk. However, the modification effects of genetic susceptibility were not found. CONCLUSIONS: Long-term exposure to ambient ozone increase the risk of mental disorders among the middle aged and older adults, and omega-3 fatty acid could reduce the adverse effects of ozone on mental health. Higher intake of omega-3 fatty acid is a potential strategy to prevent the risks caused by ozone on public mental health.

A tau class glutathione S-transferase in tea plant, CsGSTU45, facilitates tea plant susceptibility to Colletotrichum camelliae infection mediated by jasmonate signaling pathway.

Tea plant [Camellia sinensis (L.) O. Kuntze], as one of the most important commercial crops, frequently suffers from anthracnose caused by Colletotrichum camelliae. The plant-specific tau (U) class of glutathione S-transferases (GSTU) participates in ROS homeostasis. Here, we identified a plant-specific GST tau class gene from tea plant, CsGSTU45, which is induced by various stresses, including C. camelliae infection, by analyzing multiple transcriptomes. CsGSTU45 plays a negative role in disease resistance against C. camelliae by accumulating H2 O2 . JA negatively regulates the resistance of tea plants against C. camelliae, which depends on CsGSTU45. CsMYC2.2, which is the key regulator in the JA signaling pathway, directly binds to and activates the promoter of CsGSTU45. Furthermore, silencing CsMYC2.2 increased disease resistance associated with reduced transcript and protein levels of CsGSTU45, and decreased contents of H2 O2 . Therefore, CsMYC2.2 suppresses disease resistance against C. camelliae by binding to the promoter of the CsGSTU45 gene and activating CsGSTU45. CsJAZ1 interacts with CsMYC2.2. Silencing CsJAZ1 attenuates disease resistance, upregulates the expression of CsMYC2.2 elevates the level of the CsGSTU45 protein, and promotes the accumulation of H2 O2 . As a result, CsJAZ1 interacts with CsMYC2.2 and acts as its repressor to suppress the level of CsGSTU45 protein, eventually enhancing disease resistance in tea plants. Taken together, the results show that the JA signaling pathway mediated by CsJAZ1-CsMYC2.2 modulates tea plant susceptibility to C. camelliae by regulating CsGSTU45 to accumulate H2 O2 .

Effect of hyperbaric oxygen on the growth and susceptibility of facultatively anaerobic bacteria and bacteria with oxidative metabolism to selected antibiotics.

Wild strains of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were tested in an experimental hyperbaric chamber to determine the possible effect of hyperbaric oxygen on the susceptibility of these strains to the antibiotics ampicillin, ampicillin + sulbactam, cefazolin, cefuroxime, cefoxitin, gentamicin, sulfamethoxazole + trimethoprim, colistin, oxolinic acid, ofloxacin, tetracycline, and aztreonam during their cultivation at 23 °C and 36.5 °C. Ninety-six-well inoculated microplates with tested antibiotics in Mueller-Hinton broth were cultured under standard incubator conditions (normobaric normoxia) for 24 h or in an experimental hyperbaric chamber (HAUX, Germany) for 24 h at 2.8 ATA of 100% oxygen (hyperbaric hyperoxia). The hyperbaric chamber was pressurised with pure oxygen (100%). Both cultures (normoxic and hyperoxic) were carried out at 23 °C and 36.5 °C to study the possible effect of the cultivation temperature. No significant differences were observed between 23 and 36.5 °C cultivation with or without the 2-h lag phase in Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Cultivation in a hyperbaric chamber at 23 °C and 36.5 °C with or without a 2-h lag phase did not produce significant changes in the minimum inhibitory concentration (MIC) of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. For the tested strains of Pseudomonas aeruginosa, the possible effect of hyperbaric oxygen on their antibiotic sensitivity could not be detected because the growth of these bacteria was completely inhibited by 100% hyperbaric oxygen at 2.8 ATA under all hyperbaric conditions tested at 23 °C and 36.5 °C. Subsequent tests with wild strains of pseudomonads, burkholderias, and stenotrophomonads not only confirmed the fact that these bacteria stop growing under hyperbaric conditions at a pressure of 2.8 ATA of 100% oxygen but also indicated that inhibition of growth of these bacteria under hyperbaric conditions is reversible.

Multimodal diagnostics for keratoconus and ectatic corneal diseases: a paradigm shift.

Different diagnostic approaches for ectatic corneal diseases (ECD) include screening, diagnosis confirmation, classification of the ECD type, severity staging, prognostic evaluation, and clinical follow-up. The comprehensive assessment must start with a directed clinical history. However, multimodal imaging tools, including Placido-disk topography, Scheimpflug three-dimensional (3D) tomography, corneal biomechanical evaluations, and layered (or segmental) tomography with epithelial thickness by optical coherence tomography (OCT), or digital very high-frequency ultrasound (dVHF-US) serve as fundamental complementary exams for measuring different characteristics of the cornea. Also, ocular wavefront analysis, axial length measurements, corneal specular or confocal microscopy, and genetic or molecular biology tests are relevant for clinical decisions. Artificial intelligence enhances interpretation and enables combining such a plethora of data, boosting accuracy and facilitating clinical decisions. The applications of diagnostic information for individualized treatments became relevant concerning the therapeutic refractive procedures that emerged as alternatives to keratoplasty. The first paradigm shift concerns the surgical management of patients with ECD with different techniques, such as crosslinking and intrastromal corneal ring segments. A second paradigm shift involved the quest for identifying patients at higher risk of progressive iatrogenic ectasia after elective refractive corrections on the cornea. Beyond augmenting the sensitivity to detect very mild (subclinical or fruste) forms of ECD, ectasia risk assessment evolved to characterize the inherent susceptibility for ectasia development and progression. Furthermore, ectasia risk is also related to environmental factors, including eye rubbing and the relational impact of the surgical procedure on the cornea.

Granular architecture of lotus seed starch and its impact on physicochemical properties.

Lotus seed starch has high apparent amylose content (AAM). A representative definition of its granular architecture (e.g., lamellar structure) remained absent. This study defined the granular shape, crystalline and lamellar structures, and digestibility of twenty-two samples of lotus seed starch (LS) by comparing with those of potato and maize starches. LS granules had more elongated shape and longer repeat distance of lamellae than potato and maize starch granules. The enzymatic susceptibility of LS granules was more affected by AAM than granular architecture. Using these LSs as a model system, the relationships between lamellar structure of starch granules and properties of their gelatinized counterparts were investigated. In LSs, thinner amorphous lamella and thicker crystalline lamella were associated with higher swelling power and yield stress. The relationships were found to be connected via certain structural characteristics of amylopectin.

Artemisia brevifolia Wall. Ex DC Enhances Cefixime Susceptibility by Reforming Antimicrobial Resistance.

(1) Background: A possible solution to antimicrobial resistance (AMR) is synergism with plants like Artemisia brevifolia Wall. ex DC. (2) Methods: Phytochemical quantification of extracts (n-hexane (NH), ethyl acetate (EA), methanol (M), and aqueous (Aq)) was performed using RP-HPLC and chromogenic assays. Extracts were screened against resistant clinical isolates via disc diffusion, broth dilution, the checkerboard method, time-kill, and protein quantification assays. (3) Results: M extract had the maximum phenolic (15.98 ± 0.1 µg GAE/mgE) and flavonoid contents (9.93 ± 0.5 µg QE/mgE). RP-HPLC displayed the maximum polyphenols in the M extract. Secondary metabolite determination showed M extract to have the highest glycosides, alkaloids, and tannins. Preliminary resistance profiling indicated that selected isolates were resistant to cefixime (MIC 20-40 µg/mL). Extracts showed moderate antibacterial activity (MIC 60-100 µg/mL). The checkerboard method revealed a total synergy between EA extract and cefixime with 10-fold reductions in cefixime dose against resistant P. aeruginosa and MRSA. Moreover, A. brevifolia extracts potentiated the antibacterial effect of cefixime after 6 and 9 h. The synergistic combination was non- to slightly hemolytic and could inhibit bacterial protein in addition to cefixime disrupting the cell wall, thus making it difficult for bacteria to survive. (4) Conclusion: A. brevifolia in combination with cefixime has the potential to inhibit AMR.

Rapid Mycobacterium abscessus antimicrobial susceptibility testing based on antibiotic treatment response mapping via Raman Microspectroscopy.

OBJECTIVES: Antimicrobial susceptibility tests (ASTs) are pivotal tools for detecting and combating infections caused by multidrug-resistant rapidly growing mycobacteria (RGM) but are time-consuming and labor-intensive. DESIGN: We used a Mycobacterium abscessus-based RGM model to develop a rapid (24-h) AST from the beginning of the strain culture, the Clinical Antimicrobials Susceptibility Test Ramanometry for RGM (CAST-R-RGM). The ASTs obtained for 21 clarithromycin (CLA)-treated and 18 linezolid (LZD)-treated RGM isolates. RESULTS: CAST-R-RGM employs D2O-probed Raman microspectroscopy to monitor RGM metabolic activity, while also revealing bacterial antimicrobial drug resistance mechanisms. The results of clarithromycin (CLA)-treated and linezolid (LZD)-treated RGM isolates exhibited 90% and 83% categorical agreement, respectively, with conventional AST results of the same isolates. Furthermore, comparisons of time- and concentration-dependent Raman results between CLA- and LZD-treated RGM strains revealed distinct metabolic profiles after 48-h and 72-h drug treatments, despite similar profiles obtained for both drugs after 24-h treatments. CONCLUSIONS: Ultimately, the rapid, accurate, and low-cost CAST-R-RGM assay offers advantages over conventional culture-based ASTs that warrant its use as a tool for improving patient treatment outcomes and revealing bacterial drug resistance mechanisms.

Sensibilidad de Escherichia coli frente a fosfomicina, en infecciones urinarias provenientes de personas con discapacidad que acudieron a la Secretaría Nacional por los Derechos Humanos de las Personas con Discapacidad-SENADIS / Susceptibility of Escherichia coli against fosfomycin in urinary tract infections from people with disabilities who attended SENADIS

INTRODUCCIÓN: Fosfomicina es un antimicrobiano de amplio espectro utilizado para el tratamiento de las infecciones urinarias bajas; tiene actividad sobre bacilos gramnegativos y cocos grampositivos, así también sobre microorganismos multirresistentes, además de ofrecer una alternativa terapéutica de administración vía oral en dosis única, alcanzando una efectividad de 90%. OBJETIVO: Conocer la sensibilidad in vitro de Escherichia coli frente a fosfomicina, en infecciones urinarias provenientes de personas con discapacidad. MATERIAL Y MÉTODO: Estudio observacional, descriptivo, prospectivo, en el que se incluyó un total de 273 muestras de urocultivo, de pacientes de ambos sexos que acudieron a SENADIS, y que en el momento de la consulta presentaban síntomas de infección del tracto urinario, por lo que se les solicitó el análisis de orina simple y cultivo. De las muestras procesadas en el laboratorio de microbiología, que fueron positivas con crecimiento bacteriano significativo, se procedió a la identificación bacteriana y a la realización del antibiograma según las recomendaciones de CLSI. RESULTADOS: De estas 273 muestras, 91 fueron positivas para diferentes uropatógenos, 62/91 (68%) resultaron ser E. coli. De estas cepas de E. coli, 59/62 (95%) mostraron sensibilidad in vitro a fosfomicina. Comentario: Aunque el número de muestra obtenido es pequeño y no extrapolable ampliamente, pretendemos extender el trabajo por un tiempo más para compararlo más adelante. CONCLUSIONES: Se observa que fosfomicina presenta buena actividad in vitro frente a cepas de E. coli aisladas de urocultivo, pudiendo representar una buena alternativa terapéutica a ser utilizada en la población en estudio.

BACKGROUND: Fosfomycin is a broad-spectrum antibiotic used for the treatment of lower urinary tract infections, it is active against gramnegative bacilli and grampositive cocci, as well as against multi-resistant microorganism, in addition to offering a therapeutic alternative for oral administration in a single dose, reaching an effectiveness of 90%. AIM: To study the susceptibility of Escherichia coli to fosfomycin in urinary tract infections, of isolated strains obtained from patients with disabilities. METHODS: It is an observational, descriptive, prospective study in which a total of 273 urine culture samples of patients of both sexes who attended the SENADIS were included, and who at the time of the consultation presented symptoms of urinary tract infection. The urine positive cultures with significant bacterial growth were performed to determine its bacterial identification and the antibiogram according to CLSI recommendations. RESULTS: Of these 273 samples, 91 samples were positive for different uropathogens, with 62/91 (68%) being positive for E. coli. Of these E. coli strains, 59/62 (95%) showed in vitro susceptibility to fosfomycin. Comment: Although the number of samples obtained is small and it cannot be extrapolated, we pretend to extend the work for a while longer to be able to compare it later. CONCLUSION: Fosfomycin has good activity in vitro against E. coli isolated from urine culture in our institution, representing a good alternative to be used in our study population

The diamagnetic component map from quantitative susceptibility mapping (QSM) source separation reveals pathological alteration in Alzheimer's disease-driven neurodegeneration.

A sensitive and accurate imaging technique capable of tracking the disease progression of Alzheimer's Disease (AD) driven amnestic dementia would be beneficial. A currently available method for pathology detection in AD with high accuracy is Positron Emission Tomography (PET) imaging, despite certain limitations such as low spatial resolution, off-targeting error, and radiation exposure. Non-invasive MRI scanning with quantitative magnetic susceptibility measurements can be used as a complementary tool. To date, quantitative susceptibility mapping (QSM) has widely been used in tracking deep gray matter iron accumulation in AD. The present work proposes that by compartmentalizing quantitative susceptibility into paramagnetic and diamagnetic components, more holistic information about AD pathogenesis can be acquired. Particularly, diamagnetic component susceptibility (DCS) can be a powerful indicator for tracking protein accumulation in the gray matter (GM), demyelination in the white matter (WM), and relevant changes in the cerebrospinal fluid (CSF). In the current work, voxel-wise group analysis of the WM and the CSF regions show significantly lower |DCS| (the absolute value of DCS) value for amnestic dementia patients compared to healthy controls. Additionally, |DCS| and τ PET standardized uptake value ratio (SUVr) were found to be associated in several GM regions typically affected by τ deposition in AD. Therefore, we propose that the separated diamagnetic susceptibility can be used to track pathological neurodegeneration in different tissue types and regions of the brain. With the initial evidence, we believe the usage of compartmentalized susceptibility demonstrates substantive potential as an MRI-based technique for tracking AD-driven neurodegeneration.