L eishmaniasis is a prevalent disease that impacts 98 countries and territories, mainly in Africa, Asia, and South America. It can cause substantial illness and death, particularly in its visceral manifestation that can be specifically targeted in the development of medications to combat leishmaniasis. This study has found natural compounds with possible inhibitory activity against APX using a reliable and accurate QSAR model. Despite the severe side effects of current treatments and the absence of an effective vaccination, these compounds show promise as a potential treatment for the disease. Nine hit compounds were found, and subsequent molecular docking was performed. Estradiol cypionate showed the lowest binding energy (- 10.5 kcal/mol), thus showing the strongest binding, and also had the strongest binding affinity, with a ΔGTotal of - 26.31 ± 3.01 kcal/mol, second only to the control molecule. Additionally, three hits viz. cloxacillin-sodium (- 16.57 ± 2.89 kcal/mol), cinchonidine (- 16.04 ± 3.27 kcal/mol), and quinine hydrochloride dihydrate (13.38 ± 1.06 kcal/mol) also showed significant binding affinity. Multiple interactions between drugs and active site residues demonstrated a substantial binding affinity with the target protein. The identified compounds exhibited drug-like effects and were orally bioavailable based on their ADME-toxicology features. Overall, estradiol cypionate, cloxacillin sodium, cinchonidine, and quinine hydrochloride dihydrate all exhibited inhibitory effects on the APX enzyme of Leishmania donovani. These results suggest that further investigation is needed to explore the potential of developing novel anti-leishmaniasis drugs using these compounds.
- MeSH
- Antiprotozoal Agents * pharmacology chemistry MeSH
- Enzyme Inhibitors * pharmacology chemistry MeSH
- Quantitative Structure-Activity Relationship MeSH
- Leishmaniasis * drug therapy MeSH
- Humans MeSH
- Molecular Docking Simulation MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: The aim of our study was to study the association between end-of-surgery facial nerve stimulation threshold and extent of tumor resection in case of grade IV vestibular schwannomas. MATERIALS AND METHODS: Grade IV VSs represent a surgical challenge as a risk/benefit ratio must be considered in balancing a satisfactory extent of resection against a good postoperative functional outcome. We reviewed a cumulative series of 57 patients with large/giant VSs who were operated on by retrosigmoid approach in the period from 2008 to 2018 in two European centers, namely San Filippo Neri Hospital, Rome, Italy and Masaryk Hospital, Usti nad Labem, Czech Republic. Extent of resection, intraoperative direct electrical stimulation threshold of facial nerve and postoperative facial outcome were examined. RESULTS: Total or near-total resection was accomplished in 40 (75.5%) cases. Two groups were compared: total or near-total resection (T + NT) and subtotal resection (ST); the end-of-surgery facial nerve stimulation threshold significantly differed (T + NT: 0.24 mA, ST: 0.44 mA, p = 0.036). A critical cutoff was found at 0.2mA; values similar or inferior to this correctly predicted total or near-total resection in 86.7% of cases. Thirty (56.6%) patients had a normal postoperative facial outcome (HB1). Among the 40 patients in T + NT group, 32 (80%) retained an acceptable facial function (HB1-2). CONCLUSIONS: Lower facial nerve stimulation thresholds positively predict a broader extent of resection and total or -near total resection should be accomplished in such cases. Judicious (subtotal) resection is preferred if threshold values increase while dissecting firmly adherent tumors.
- MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Facial Nerve physiopathology MeSH
- Neurosurgical Procedures * methods MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Neoplasm Grading MeSH
- Neuroma, Acoustic * surgery MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- Czech Republic MeSH
BACKGROUND: Existing radiological markers of hematoma expansion (HE) show modest predictive accuracy. We aim to investigate a novel radiological marker that co-localizes findings from non-contrast CT (NCCT) and CT angiography (CTA) to predict HE. METHODS: Consecutive acute intracerebral hemorrhage patients admitted at Foothills Medical Centre in Calgary, Canada, were included. The Black-&-White sign was defined as any visually identified spot sign on CTA co-localized with a hypodensity sign on the corresponding NCCT. The primary outcome was hematoma expansion (⩾6 mL or ⩾33%). Secondary outcomes included absolute (<3, 3-6, 6-12, ⩾12 mL) and relative (0%, <25%, 25%-50%, 50%-75%, or >75%) hematoma growth scales. RESULTS: Two-hundred patients were included, with 50 (25%) experiencing HE. Forty-four (22%) showed the spot sign, 69 (34.5%) the hypodensity sign, and 14 (7%) co-localized both as the Black-&-White sign. Those with the Black-&-White sign had higher proportions of HE (100% vs 19.4%, p < 0.001), greater absolute hematoma growth (23.37 mL (IQR = 15.41-30.27) vs 0 mL (IQR = 0-2.39), p < 0.001) and relative hematoma growth (120% (IQR = 49-192) vs 0% (0-15%), p < 0.001). The Black-&-White sign had a specificity of 100% (95%CI = 97.6%-100%), a positive predictive value of 100% (95%CI = 76.8%-100%), and an overall accuracy of 82% (95%CI = 76%-87.1%). Among the 14 patients with the Black-&-White sign, 13 showed an absolute hematoma growth ⩾12 mL, and 10 experienced a HE exceeding 75% of the initial volume. The inter-rater agreement was excellent (kappa coefficient = 0.84). CONCLUSION: The Black-&-White sign is a robust predictor of hematoma expansion occurrence and severity, yet further validation is needed to confirm these compelling findings.
- MeSH
- Cerebral Hemorrhage * diagnostic imaging MeSH
- Computed Tomography Angiography * methods MeSH
- Hematoma * diagnostic imaging MeSH
- Middle Aged MeSH
- Humans MeSH
- Cerebral Angiography * methods MeSH
- Tomography, X-Ray Computed * methods MeSH
- Predictive Value of Tests MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Euglenids have long been studied due to their unique physiology and versatile metabolism, providing underpinnings for much of our understanding of photosynthesis and biochemistry, and a growing opportunity in biotechnology. Until recently there has been a lack of genetic studies due to their large and complex genomes, but recently new technologies have begun to unveil their genetic capabilities. Whilst much research has focused on the model organism Euglena gracilis, other members of the euglenids have now started to receive due attention. Currently only poor nuclear genome assemblies of E. gracilis and Rhabdomonas costata are available, but there are many more plastid genome sequences and an increasing number of transcriptomes. As more assemblies become available, there are great opportunities to understand the fundamental biology of these organisms and to exploit them for biotechnology.
BACKGROUND: Pulsed field ablation (PFA) of atrial fibrillation is a new method in clinical practice. Despite a favorable safety profile of PFA in atrial fibrillation ablation, rare cases of renal failure, probably due to hemolysis, have recently been reported. OBJECTIVE: The aim of this study was to determine the rate of hemolysis and cardiac cell death during in vitro PFA with different electric field intensities. METHODS: Blood samples from healthy volunteers and mouse HL-1 cardiomyocyte cell lines were subjected to in vitro irreversible electroporation using 216 bipolar pulses, each lasting 2 μs with intervals of 5 μs, repeated 20 times at a frequency of 1 Hz. These pulses varied from 500 V to 1500 V. Cell-free hemoglobin levels were assessed spectrophotometrically, and red blood cell microparticles were evaluated by flow cytometry. Cardiomyocyte death was quantified with propidium iodide. RESULTS: Pulsed field energy (1000 V/cm, 1250 V/cm, and 1500 V/cm) was associated with a significant increase in cell-free hemoglobin (0.32 ± 0.16 g/L, 2.2 ± 0.96 g/L, and 5.7 ± 0.39 g/L; P < .01) and similar increase in the concentration of red blood cell microparticles. Significant rates of cardiomyocyte death were observed at electric field strengths of 750 V/cm, 1000 V/cm, 1250 V/cm, and 1500 V/cm (26.5% ± 5.9%, 44.3% ± 6.2%, 55.5% ± 6.9%, and 74.5% ± 17.8% of cardiomyocytes; P < .01). CONCLUSION: The most effective induction of cell death in vitro was observed at 1500 V/cm. This intensity was also associated with a significant degree of hemolysis.
- MeSH
- Electroporation * methods MeSH
- Atrial Fibrillation physiopathology surgery MeSH
- Hemolysis * physiology MeSH
- Myocytes, Cardiac * metabolism MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Mice MeSH
- Flow Cytometry MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND AND OBJECTIVES: En bloc sacrectomy is associated with sacral root transection causing loss of urinary bladder, rectum, and sexual function. The aim of the study was to determine the position of the pudendal branches (sensorimotor) and pelvic splanchnic nerves (parasympathetic) on the sacral roots relative to the sacrum, and the minimal and maximal defects in the sacral roots that can be reconstructed by grafting after various types of sacrectomy. METHODS: Five cadaveric pelves were dissected bilaterally. The lengths and widths of the S1-S4 roots and their branches were measured. Then, the minimal and maximal defects between the proximal and distal stumps of the sacrificed roots were measured following 3 models of sacrectomy (below S2, below S1, and total sacrectomy). RESULTS: The mean distance of the splanchnic nerves from the S2 and S3 anterior sacral foramina was 17.7 ± 7.3 and 23.6 ± 11.1 mm, respectively, and the mean distance of the pudendal S2 and S3 branches was 36.8 ± 13.7 and 30.2 ± 10.8 mm, respectively. The mean widths of the S2 and S3 roots were 9.3 ± 1.9 and 5.4 ± 1.2 mm, respectively. The mean maximal defects in S2 and S3 roots after various types of sacrectomies were between 61.8 ± 16.3 and 100.7 ± 14.3 mm and between 62.7 ± 20.2 and 84.7 ± 25.1 mm, respectively. There were no statistically significant differences between sides or sexes for all obtained measurements. CONCLUSION: The reconstruction of the S2-S3 roots is anatomically feasible after partial or total sacrectomies in which the resection of the soft tissue does not extend further than approximately 1.5 to 2 cm ventrally from the sacrum.
- MeSH
- Sacrum * surgery anatomy & histology innervation MeSH
- Middle Aged MeSH
- Humans MeSH
- Spinal Nerve Roots * anatomy & histology surgery MeSH
- Cadaver * MeSH
- Aged MeSH
- Splanchnic Nerves anatomy & histology surgery MeSH
- Plastic Surgery Procedures methods MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: Differentiating true progression or recurrence (TP/TR) from therapy-related changes (TRC) is complex in brain tumours. Amide proton transfer-weighted (APT) imaging is a chemical exchange saturation transfer (CEST) MRI technique that may improve diagnostic accuracy during radiological follow-up. This systematic review and meta-analysis elucidated the level of evidence and details of state-of-the-art imaging for APT-CEST in glioma and brain metastasis surveillance. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for original articles about glioma and metastasis patients who received APT-CEST imaging for suspected TP/TR within 2 years after (chemo)radiotherapy completion. Modified Quality Assessment of Diagnostic Accuracy Studies-2 criteria were applied. A meta-analysis was performed to pool results and to compare subgroups. RESULTS: Fifteen studies were included for a narrative synthesis, twelve of which (500 patients) were deemed sufficiently homogeneous for a meta-analysis. Magnetisation transfer ratio asymmetry performed well in gliomas (sensitivity 0.88 [0.82-0.92], specificity 0.84 [0.72-0.91]) but not in metastases (sensitivity 0.64 [0.38-0.84], specificity 0.56 [0.33-0.77]). APT-CEST combined with conventional/advanced MRI rendered 0.92 [0.86-0.96] and 0.88 [0.72-0.95] in gliomas. Tumour type, TR prevalence, sex, and acquisition protocol were sources of significant inter-study heterogeneity in sensitivity (I2 = 62.25%; p < 0.01) and specificity (I2 = 66.31%; p < 0.001). CONCLUSION: A growing body of literature suggests that APT-CEST is a promising technique for improving the discrimination of TP/TR from TRC in gliomas, with limited data on metastases. CLINICAL RELEVANCE STATEMENT: This meta-analysis identified a utility for APT-CEST imaging regarding the non-invasive discrimination of brain tumour progression from therapy-related changes, providing a critical evaluation of sequence parameters and cut-off values, which can be used to improve response assessment and patient outcome. KEY POINTS: Therapy-related changes mimicking progression complicate brain tumour treatment. Amide proton imaging improves the non-invasive discrimination of glioma progression from therapy-related changes. Magnetisation transfer ratio asymmetry measurement seems not to have added value in brain metastases.
- MeSH
- Amides * MeSH
- Diagnosis, Differential MeSH
- Glioma * diagnostic imaging pathology MeSH
- Humans MeSH
- Neoplasm Recurrence, Local diagnostic imaging MeSH
- Magnetic Resonance Imaging * methods MeSH
- Brain Neoplasms * diagnostic imaging secondary MeSH
- Disease Progression * MeSH
- Protons MeSH
- Sensitivity and Specificity MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Systematic Review MeSH
