Acetylmelodorinol isolated from Sphaerocoryne affinis seeds inhibits cell proliferation and activates apoptosis on HeLa cells.

BACKGROUND: Cervical cancer is a major global health concern with a high prevalence in low- and middle-income countries. Natural products, particularly plant-derived compounds, have shown immense potential for developing anticancer drugs. In this study, we aimed to investigate the anticancer properties of the pericarp and seeds of Sphaerocoryne affinis fruit on human cervical carcinoma cells (HeLa) and isolate the bioactive compound from the active fraction. METHODS: We prepared solvent fractions from the ethanol extracts of the pericarp and the seed portion by partitioning and assessing their cytotoxicity on HeLa cells. Subsequently, we collected acetylmelodorinol (AM), an anticancer compound, from the ethyl acetate fraction of seeds and determined its structure using nuclear magnetic resonance. We employed cytotoxicity assay, western blotting, Annexin V apoptosis assay, measurement of intracellular reactive oxygen species (ROS) levels, 4',6-diamidino-2-phenylindole (DAPI) staining, and a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, to evaluate the anticancer properties of AM on HeLa. RESULTS: The solvent fractions from the seed displayed considerably higher cytotoxic activity against HeLa cells than those of the pericarp. We isolated and identified acetylmelodorinol as an anticancer compound from the ethyl acetate fraction from S. affinis seed extract. Treatment with acetylmelodorinol inhibited HeLa cell proliferation with an IC50 value of 2.62 ± 0.57 µg/mL. Furthermore, this study demonstrated that acetylmelodorinol treatment disrupted cell cycle progression by reducing the expression of cyclin E, CDK1/2, and AKT/mTOR pathways, increasing the intracellular ROS levels, reducing BCL-2/BCL-XL expression, causing DNA fragmentation and nuclear shrinkage, and triggering apoptosis through caspase 3 and 9 activation in a dose-and time-dependent manner. CONCLUSION: In contrast to previous reports, this study focuses on the inhibitory effects of AM on the AKT/mTOR pathway, leading to a reduction in cell proliferation in cervical cancer cells. Our findings highlight the promising potential of acetylmelodorinol as an effective treatment for cervical cancer. Additionally, this study establishes a foundation for investigating the molecular mechanisms underlying AM's properties, fostering further exploration into plant-based cancer therapies.

Anti-inflammatory, anti-tussive effects and toxicity evaluation of Qingfei Dayuan granules.

OBJECTIVE: To study the anti-inflammatory and anti-tussive effects of Qingfei Dayuan granules (, QFDY), and to evaluate the acute and sub-chronic toxicity of QFDY. METHODS: Anti-inflammatory effects were evaluated by murine model of xylene induced ear edema in mice. Ear swelling degree was calculated and tumor necrosis factor-α, interleukin-1ß and interleukin-6 were determined. Anti-tussive evaluations were carried out in the mouse cough model induced by ammonia liquor. Latent period cough and number of cough within 3 min were counted. In acute toxicity study, the rats were randomly divided into test group and solvent control group. Body weighs, food intakes and general clinical signs were monitored. In the sub-chronic toxicity study, QFDY was administered to rats at 0, 4, 8 and 16 g/kg per day for 28 and 30 d of post treatment was conducted. Mortalities, clinical signs, body weight changes, food intakes, ophthalmological examinations, hematological parameters, biochemical indicators, electrolyte indicators, urinalyses and histopathological examinations were monitored. RESULTS: QFDY significantly inhibited the development of ear edema in anti-inflammatory assay and decreased cough frequency caused by ammonia liquor. The results presented a dose-effect relationship. In acute toxicity study, no abnormality exhibited at dose of 24.0 g/kg per day during the 14-d observation period. In the sub-chronic toxicity study, higher reticulocyte count, lymphocyte and lower Cl-, blood urea nitrogen were analyzed compared with the solvent control group. But the differences were considered to be incidental and not clinically toxic. Obvious dose-effect relationship of urine color was observed, and the three test groups at the end of the experiments resulted in significant increase in urobilinogen, bilirubin, ketone body and urine leukocyte. However, all the positive indicators returned to normal in the recovery period. Therefore, no toxicological changes were found during the study period. CONCLUSION: QFDY showed significant anti-inflammatory and anti-tussive effects in mice. The lethal dose (LD50) of per oral QFDY in rats was estimated to be more than 24.0 g/kg per day and the no observed adverse effect level was over 16 g/kg per day, which suggested that QFDY is relatively safe for oral medication at the present dose on rats. Our experimental results provide a reference for the further development and research of QFDY.

Apoptosis-Mediated Anticancer Activity of Ganoderma colossus (Agaricomycetes) Extracts in Breast Cancer Cells.

Cancer is a leading cause of death worldwide. The current cancer treatments including chemo-, radio- and immuno-therapies pose various side effects, and chances of recurrence that demand for new therapeutics to overcome the issues with existing ones. Mushrooms are considered a potential source of novel therapeutic agents. Ganoderma colossus, a non-edible wood-inhabiting mushroom, is known for certain medical properties. The present study aimed to investigate the possible anticancer activity of methanolic, ethyl acetate, and chloroform extracts of G. colossus, against MCF-7 cells and the mechanism of action(s). MTT assay and gene expression studies were carried out by following the standard protocols. The results demonstrated that among the three solvents, the ethyl acetate crude extract of the mushroom exhibited potential cytotoxic activity on MCF-7 (IC50, 17.2 ± 2.7). The DNA damage induced by the solvent extracts of G. colossus was observed by H2AX foci formation. The TP53 over-expression and flow cytometry analysis indicated that checkpoint activation followed by cell cycle arrest occurred at G1/G0 phase in response to the extract treatment. The dual acridine orange/ethidium bromide (AO/EB) staining revealed apoptosis-associated changes in the cells. Analysis of caspase 3 activations by immunophenotyping confirmed the apoptotic process in the extract-treated cells. Bcl-2 and TP53 mRNA expression data by RT-PCR disclosed the apoptosis pathway. The GC- MS spectral data of the ethyl acetate crude extract of the mushroom indicated the presence of molecules capable of inducing apoptosis. The present study warrants further studies to isolate the molecule(s) from G. colossus which may be a potential drug candidate for breast cancers.

Nab-paclitaxel weekly versus dose-dense solvent-based paclitaxel followed by dose-dense epirubicin plus cyclophosphamide in high-risk HR+/HER2- early breast cancer: results from the neoadjuvant part of the WSG-ADAPT-HR+/HER2- trial.

BACKGROUND: In high-risk hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC), nanoparticle albumin-bound (nab)-paclitaxel showed promising efficacy versus solvent-based (sb)-paclitaxel in neoadjuvant trials; however, optimal patient and therapy selection remains a topic of ongoing research. Here, we investigate the potential of Oncotype DX® recurrence score (RS) and endocrine therapy (ET) response (low post-endocrine Ki67) for therapy selection. PATIENTS AND METHODS: Within the WSG-ADAPT trial (NCT01779206), high-risk HR+/HER2- EBC patients were randomized to (neo)adjuvant 4× sb-paclitaxel 175 mg/m2 q2w or 8× nab-paclitaxel 125 mg/m2 q1w, followed by 4× epirubicin + cyclophosphamide (90 mg + 600 mg) q2w; inclusion criteria: (i) cN0-1, RS 12-25, and post-ET Ki67 >10%; (ii) cN0-1 with RS >25. Patients with cN2-3 or (G3, baseline Ki67 ≥40%, and tumor size >1 cm) were allowed to be included without RS and/or ET response testing. Associations of key factors with pathological complete response (pCR) (primary) and survival (secondary) endpoints were analyzed using statistical mediation and moderation models. RESULTS: Eight hundred and sixty-four patients received neoadjuvant nab-paclitaxel (n= 437) or sb-paclitaxel (n = 427); nab-paclitaxel was superior for pCR (20.8% versus 12.9%, P = 0.002). pCR was higher for RS >25 versus RS ≤25 (16.0% versus 8.4%, P = 0.021) and for ET non-response versus ET response (15.1% versus 6.0%, P = 0.027); no factors were predictive for the relative efficacy of nab-paclitaxel versus sb-paclitaxel. Patients with pCR had longer distant disease-free survival [dDFS; hazard ratio 0.42, 95% confidence interval (CI) 0.20-0.91, P = 0.024]. Despite favorable prognostic association of RS >25 versus RS ≤25 with pCR (odds ratio 3.11, 95% CI 1.71-5.63, P ≤ 0.001), higher RS was unfavorably associated with dDFS (hazard ratio 1.03, 95% CI 1.01-1.05, P = 0.010). CONCLUSIONS: In high-risk HR+/HER2- EBC, neoadjuvant nab-paclitaxel q1w appears superior to sb-paclitaxel q2w regarding pCR. Combining RS and ET response assessment appears to select patients with highest pCR rates. The disadvantage of higher RS for dDFS is reduced in patients with pCR. These are the first results from a large neoadjuvant randomized trial supporting the use of RS to help select patients for neoadjuvant chemotherapy in high-risk HR+/HER2- EBC.

Cuscuta reflexa Possess Potent Inhibitory Activity Against Human Malaria Parasite: An In Vitro and In Vivo Study.

Drug resistance to practically all antimalarial drugs in use necessitate the development of new chemotherapeutics against malaria. In this aspect, traditionally used plants with folklore reputation are the pillar for drug discovery. Cuscuta reflexa being traditionally used in the treatment of malaria in Odisha, India we aimed to experimentally validate its antimalarial potential. Different solvent extracts of C. reflexa or column fractions from a promising solvent extract were evaluated for in vitro anti-plasmodial activity against Plasmodium falciparum strain Pf3D7. Potent fractions were further evaluated for inhibition of parasite growth against different drug resistant strains. Safety of these fractions was determined by in vitro cyto-toxicity, and therapeutic effectiveness was evaluated by suppression of parasitemia and improvement in survival of experimental mice. Besides, their immunomodulatory effect was investigated in Pf-antigen stimulated RAW cells. GCMS fingerprints of active fractions was determined. Column separation of methanol extract which showed the highest in vitro antiplasmodial activity (IC50 = 14.48 µg/ml) resulted in eleven fractions, three of which (F2, F3, and F4) had anti-plasmodial IC50 ranging from ≤ 10 to 2.2 µg/ml against various P. falciparum strains with no demonstration of in vitro cytotoxicity. F4 displayed the highest in vivo parasite suppression, and had a mean survival time similar to artesunate (19.3 vs. 20.6 days). These fractions significantly modulated expression of inflammatory cytokines in Pf-antigen stimulated RAW cells. The findings of the study confirm the antimalarial potential of C. reflexa. Exploration of phyto-molecules in GCMS fingerprints of active fractions is warranted for possible identification of lead anti-malarial phyto-drugs.

Symptomatic Diethylene Glycol Ingestion Successfully Treated with Fomepizole Monotherapy.

BACKGROUND: Diethylene glycol (DEG) is an industrial solvent with many uses, including brake fluids. It has also caused mass poisonings after use as an inappropriate substitute for propylene glycol or glycerin, though individual ingestions are rare. Like other toxic alcohols, DEG is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase, with toxicity likely mediated by the resulting metabolites. Fomepizole, an alcohol dehydrogenase inhibitor, is used to prevent metabolite formation with other toxic alcohol exposures. Fomepizole is recommended for DEG poisoning, though supporting clinical evidence is limited. CASE REPORT: A 31-year-old man presented after ingestion of DEG-containing brake fluid and hydrocarbon-containing "octane booster." He was noted to be clinically intoxicated, with a mildly elevated anion gap metabolic acidosis and no osmolar gap. DEG level was later found to be elevated, consistent with his ingestion. He was treated with fomepizole alone, with resolution of metabolic acidosis and clinical findings over the next 2 days. No delayed neurologic sequelae were present at 52-day follow-up. Our case provides additional evidence supporting the use of fomepizole for DEG poisoning. Consistent with other toxic alcohols, DEG poisoning, especially early presentations, may benefit from empiric fomepizole administration. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: DEG poisoning is potentially life threatening, but treatable if identified early. An ingestion can be toxic despite a normal osmolar gap, leading to false reassurance. Finally, it is rare, so emergency physicians must be made aware of its potential dangers.

Antimalarial activity of solvent fractions of a leaf of Eucalyptus globulus labill against Plasmodium berghei infected mice.

INTRODUCTION: The leaf of Eucalyptus globulus is commonly used in the traditional management of malaria. However, the efficacy of solvent fractions are didn't study yet scientifically. Thus, this study aimed to investigate the antimalarial efficacy of the solvent fractions of the leaf of Eucalyptus globulus in mice against P.berghei. METHODS: The antimalarial activity of the fractions was tested in a 4-day suppressive test, Rane's test, and prophylactic test models within P.berghei infected mice. The results were analyzed using a one-way analysis of variance (ANOVA) followed by a post hoc Tukey's test in version 20 SPSS. RESULTS: All fractions at all test doses in the three test models suppressed parasitemia (p < 0.001) compared to the negative controls. In addition, the CF and EA at all three test doses and the AF at 400 mg/kg in three antimalarial test models showed 50% and above parasitemia suppression. In compliance with this, all fractions at all test doses in all test models prolonged the mean survival time of the mice greater than 12 days, except the AF at a lower dose. All fractions at 400 mg/kg in the three test models prevented (p < 0.001) loss of body weight and rectal temperature compared to the negative controls. Furthermore, all fractions in all test models and doses prevented packed cell volume reduction (p < 0.05 to p < 0.001) compared to the negative controls.. CONCLUSION: The findings of this study showed that CF and EAF had greater antimalarial activity compared to AF. This could be attributed to the presence of few phytochemicals in the AF in contrast to the CF and EAF. Overall, the results of this study further support the in vitro antimalarial activity study and the traditional use of the leaf in the management of malaria.

Antiapoptotic and antioxidative efficacy of rhizomes of Curcuma amada on the management of diabetes-induced male infertility in albino rat: An effective fraction selection study.

Men with diabetes have negative effects on reproduction that causes sexual dysfunction. Medicinal plants are non-toxic and much safer than synthetic drugs because regular use of synthetic drugs shows long-term side effects. Curcuma amada (Roxb) is a medicinal plant used in Ayurveda and Unani medicinal systems in India. The goal of this study is to rummage the potential efficiency of the most potent solvent fraction of effective extract of hydro-methanol 60:40 of C. amada rhizome on male gonadal hypofunction in streptozotocin-induced diabetic rat. Diabetes-induced testicular hypofunction was evaluated by glycemic, spermiological, biochemical, genomic, flow cytometric, and histology of testicular tissue. The n-hexane, chloroform, ethyl-acetate, and n-butanol solvent fractions of the said extract were administrated for 4 weeks at 10 mg dose/100 g body weight/day. Among all the used fractions, the ethyl-acetate solvent fraction-treated group showed maximum recovery in serum insulin (177.42%), sperm count (92.84%), sperm motility (97.15%), and serum testosterone (164.33%). The diabetic rats treated with ethyl-acetate solvent fraction also exhibited the maximum resettlement in flow cytometric analysis of sperm viability (55.84%) and sperm mitochondrial integrity (149.79%), gene expression patterns of key markers for androgenesis (Δ5, 3ß-HSD 87.50%, and 17ß-HSD 74.66%) and apoptosis (Bax 44.63%, Bcl-2 54.03%, and Caspase-3 35.77%) along with testicular histology. The ethyl-acetate fraction contains alkaloids, flavonoids, and polyphenols where all of these components are not present in other fractions, may be the most effective cause for the recovery of diabetes-linked oxidative stress-mediated testicular hypofunctions. PRACTICAL APPLICATIONS: Nowadays worldwide, the use of synthetic drugs are reduced due to their toxic effect. At present, synthetic drugs are replaced by several herbal drugs, the natural source of medicine which has many therapeutic values. C. amada has strong antioxidant activity due to the presence of bio-active compound(s) that can able to manage streptozotocin-induced diabetes linked to oxidative damage of male gonadal organs. Therefore, these bio-active compound(s)-containing said medicinal plant may use as a good source of antioxidative food in the food industry as nutraceuticals and in pharmaceutical industries for the development of the herbal drug to manage diabetes-linked male gonadal hypofunctions. At present, WHO also gives emphasis for developing one drug-multi-disease therapy. From such a viewpoint, this active fraction-containing phytomolecules may have corrective efficacy against diabetes as well as oxidative stress-linked testicular complications.

Gemini Surfactant Mediated Catansomes for Enhanced Singlet Oxygen Generation of Rose Bengal and Their Phototoxicity against Cancer Cells.

Photodynamic therapy (PDT) is an innovative technique for cancer treatment with minimal side effects, based on the use of a photosensitizer, oxygen, and light. Photosensitizers (PSs) have several limitations, that may limit their clinical use, like poor solubilization, self-aggregation, and lack of specific targeting, which can be addressed with the use of nanomaterials. Herein, a unique type of catansomes (CaSs) was prepared using a gemini imidazolium-based surfactant (1,3-bis[(3-octadecyl-1-imidazolio)methyl]benzene dibromide (GBIB) and a double chain surfactant, diaoctyl sodium sulfosuccinate or Aerosol OT (AOT). The formation of CaS GBIB/AOT was optimized in various ethanol/water (E/W) solvent ratios by employing a facile, quick, and most reliable solution-solution mixing method. The CaS was characterized by dynamic light scattering (DLS) and field emission gun scanning electron microscopy (FEG-SEM) techniques. The experimental results reveal that stable CaSs with a spherical shape were obtained at lower concentration (100 µM). Rose Bengal (RB), a PS of the xanthene family, was incorporated into these prepared CaSs, as proven by fluorescence spectroscopy, UV-visible absorption spectroscopy, and confocal laser scanning microscopy. Singlet oxygen (1O2) generation studies revealed the relevant role of the E/W solvent ratio as there was a 4-fold boost in the 1O2 production for GBIB/AOT in E/W = 50:50 and around 3-fold in E/W = 30:70. Also, the GBIB-rich 80:20 fraction was more efficient in increasing the 1O2 generation as compared to the AOT rich fraction (20:80). Further, their phototoxicity was tested in a water-rich solvent ratio (E/W = 30:70) against MCF-7 cells. Upon irradiation with a 532 nm laser (50 mW) for 5 min, RB@GBIB/AOT(20:80) fraction caused 50% decrease in the metabolic activity of MCF-7 cells, and RB@GBIB/AOT(80:20) fraction produced a maximum 85% decrease in cell viability. Furthermore, the enhancement in intracellular 1O2 generation by RB@GBIB/AOT, as compared to pure RB, was confirmed with singlet oxygen sensor green (SOSG). This new type of CaS based on gemini surfactants exhibiting a large amount of 1O2 generation, holds great interest for several applications, such as use in photomedicine in future.

Evaluation of solvent/detergent-treated plasma safety and efficacy in orthotopic liver transplant and thrombotic thrombocytopenic purpura patients: A single center experience.

BACKGROUND: Solvent/detergent-treated, pooled plasma (SDP) is approved for use in orthotopic liver transplantation (OLT) and thrombotic thrombocytopenic purpura (TTP) patients; however, studies evaluating safety and effectiveness of SDP in these populations are limited. METHODS: This prospective study included two cohorts: OLT patients (n = 40) who received either SDP (n = 20) or FFP (control group) (n = 20), and TTP patients (n = 20) who received either SDP (n = 10) or FFP (control group) (n = 10) throughout hospitalization. Medical, laboratory, and blood bank records were retroactively assessed for both cohorts for differences in clinical outcomes, laboratory values, and transfusion data from admission to discharge. RESULTS: In the OLT cohort, significant changes in AST and ALP were observed in the control group as compared to SDP (p < .05 each), and creatinine levels improved significantly in the SDP group as compared to the control group (p < .05) from admission to discharge. In the TTP cohort, platelet counts were significantly improved within the control and SDP groups from admission to discharge, but there were no significant differences between groups (p = .31). LDH levels improved between admission and discharge for both groups (70% decrease in the control group, p < .001, and 80% decrease in the SDP group, p = .001). There were no significant differences detected in clinical outcomes in either cohort. CONCLUSIONS: As evidenced by the lack of adverse events in either cohort and similar clinical outcomes, we conclude that SDP is comparable in safety and effectiveness to FFP in OLT and TTP patients. Further studies are needed to evaluate the potential for improved safety with SDP.

Adverse Event Profile for Nanoparticle Albumin-Bound Paclitaxel Compared With Solvent-Based Taxanes in Solid-Organ Tumors: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is an innovative form of taxane that has superior antitumor effects; however, the safety profile between nab-paclitaxel and traditional taxanes remains controversial. OBJECTIVE: To determine the burden of adverse events (AEs) in patients with multiple malignancies receiving nab-paclitaxel compared with that in patients receiving traditional taxanes. METHODS: Randomized clinical trials comparing nab-paclitaxel with traditional taxanes (solvent-based paclitaxel [sb-paclitaxel] or docetaxel) in the treatment of primary solid-organ malignancies were included if AEs were reported as an outcome. Statistical analyses were conducted to calculate the summary odds ratio (OR) of the relevant adverse outcomes related to nab-paclitaxel and traditional taxanes. Prespecified subgroup analyses based on intervention and doses, primary tumor sites, and different ethnic groups were also performed. RESULTS: Twelve clinical trials were included in the meta-analysis. Grade 3/4 anemia, thrombocytopenia, and neurotoxicity were more frequent with nab-paclitaxel than with traditional taxanes. Nab-paclitaxel at 100 or 125 mg/m2/w dosage was associated with fewer or similar grade 3/4 specific AEs. Allergy was less common with nab-paclitaxel. The median recovery times of neurotoxicity were 25, 64, and 37 days in patients receiving nab-paclitaxel, sb-paclitaxel, and docetaxel, respectively. Elevated incidences of specific AEs were more common in breast cancer and non-Asian patients than in other malignancies and ethnic groups, respectively. CONCLUSION AND RELEVANCE: Nab-paclitaxel increased the risk of hematologic and non-hematologic AEs in general, but anaphylaxis was less common, and the recovery duration of neurotoxicity was shorter. Weekly administration of nab-paclitaxel at a lower dosage provided better tolerance.

Comparing nanoparticle polymeric micellar paclitaxel and solvent-based paclitaxel as first-line treatment of advanced non-small-cell lung cancer: an open-label, randomized, multicenter, phase III trial.

BACKGROUND: Polymeric micellar paclitaxel (pm-Pac) is a novel Cremophor EL-free, nanoparticle micellar formulation of paclitaxel. We aimed to compare the efficacy and safety between pm-Pac plus cisplatin and solvent-based paclitaxel (sb-Pac) plus cisplatin in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 448 stage IIIB to IV NSCLC patients were randomly assigned (2:1) to receive six 3-week cycles of either pm-Pac (230 mg/m2) plus cisplatin (70 mg/m2; n = 300), followed by dose escalation of pm-Pac to 300 mg/m2 from the second 3-week cycle if prespecified toxic effects were not observed after the first cycle, or sb-Pac (175 mg/m2) plus cisplatin (70 mg/m2; n = 148). The primary end point was objective response rate (ORR) assessed by independent review committees (IRCs). The secondary end points included IRC-assessed progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Patients in the pm-Pac-plus-cisplatin group showed significant improvements in IRC-assessed ORR compared with those in the sb-Pac-plus-cisplatin group (50% versus 26%; rate ratio 1.91; P < 0.0001). Additionally, subgroup analysis showed that a higher ORR was consistently observed in both squamous and nonsquamous histological types. IRC-assessed median PFS was significantly higher in the pm-Pac-plus-cisplatin group than in the sb-Pac-plus-cisplatin group (6.4-month versus 5.3-month; hazard ratio 0.63; P = 0.0001). Median OS was not significantly different between the two groups. The incidence of treatment-related serious adverse events (9% versus 18%; P = 0.0090) was significantly lower in the pm-Pac-plus-cisplatin group than in the sb-Pac-plus-cisplatin group. CONCLUSION: Pm-Pac plus cisplatin yielded superior ORR and PFS along with a favorable safety profile and should become an option for patients with advanced NSCLC. CLINICAL TRIAL IDENTIFIER: ClinicalTrials.gov NCT02667743; https://clinicaltrials.gov/ct2/show/NCT02667743.

Alcohol intake in an attempt to fight COVID-19: A medical myth in Iran.

The coronavirus disease 2019 (COVID-19) spread rapidly worldwide and led to the deaths of thousands of people. To date, there is not any vaccine or specific antiviral medicine that can prevent or treat this virus. This caused panic among people who try their best to prevent being infected. In Iran, methanol poisoning was reported and led to the death of hundreds of people in several provinces. The incident occurred after a rumor circulated in the country that drinking alcohol (ethanol) can cure or prevent being infected by COVID-19.

Effect of solvent use on postoperative pain in root canal retreatment: a randomized, controlled clinical trial.

OBJECTIVES: The aim of this randomized clinical trial was to assess the effect of solvent use during the removal of root canal filling on postoperative pain after retreatment. MATERIALS AND METHODS: Ninety patients scheduled for root canal retreatment were randomly assigned to one of the following two groups according to the root canal filling removal procedure used: ProTaper retreatment (Dentsply Maillefer, Ballaigues, Switzerland) instruments or ProTaper retreatment instruments in combination with gutta-percha solvent. A single operator performed the retreatments in a single visit. The incidence and intensity of the postoperative pain were rated on a numeric rating scale by patients at 24, 48, and 72 h after retreatment. The analgesic tablet intake number was also recorded. Data were analyzed using Mann­Whitney U, Wilcoxon, and chi-square tests. RESULTS: For the intensity of postoperative pain, the difference between the two groups was not statistically significant. Moreover, no statistically significant difference was found between the two groups in terms of analgesic medication intake (P > 0.05). CONCLUSIONS: The processes involving the use and non-use of a solvent in the removal of root canal fillings were found to be equivalent in terms of postoperative pain intensity and analgesic intake. CLINICAL RELEVANCE: Some in vitro studies claimed that the use of a gutta-percha solvent in the removal of root canal fillings tends to reduce postoperative pain since extrusion of debris was significantly less. This randomized clinical trial indicates that the removal of root canal fillings with or without the use of a solvent was associated with equivalent postoperative pain intensity and analgesic intake. This study is registered in the www.ClinicalTrials.gov database with the identifier number NCT03756363.

Effect of Training on Percutaneous Glycerol Rhizotomy for Trigeminal Neuralgia: A Long-Term, Retrospective Comparison of Staff Neurosurgeon and Trainee Complications and Efficacy.

OBJECTIVE: The role of trainee involvement in lesioning procedures for trigeminal neuralgia (TN) has not yet been investigated in reported studies. The objective of the present study was to compare the complications and efficacy of percutaneous glycerol rhizotomy (GR) when performed by staff neurosurgeons and trainees. METHODS: A retrospective medical record analysis of 165 patients with medically refractory TN who had undergone 293 GR procedures by either a staff attending (n = 156) or trainee (n = 137) from 2007 to 2018 was performed. The data were analyzed with respect to procedure time, fluoroscopy time and radiation exposure, complication rates and outcomes. RESULTS: No difference was found in procedure duration between the teaching and nonteaching cases and only a nonsignificant trend was found toward a longer fluoroscopy time for the latter. The initial response rates to GR were equal for staff attending (88.7%) and trainee (87.2%) cases (P = 0.708). Similarly, no statistically significant difference (P = 0.48) was found between the median time to recurrence for the staff attending cases (1.6 ± 0.3 years) compared with that of the trainee cases (1.7 ± 0.3 years). The overall incidence of complications was low (7.5%). The occurrence of facial hypoesthesia correlated with the amount of glycerol injected (P < 0.01). CONCLUSIONS: GR for the treatment of TN can safely be performed by senior residents and fellows under supervision.

Management of extracranial arteriovenous malformations of the head and neck.

The purpose of this study was to review the outcomes of the different therapies for extracranial head and neck arteriovenous malformations (AVMs). AVMs are high-flow congenital vascular anomalies. They are composed of a complex system of vessels directly connecting feeding arteries to draining veins forming a nidus. They may be potentially life-threatening due to progressive symptoms and infiltrative disease. Extracranial AVMs most commonly affect the head and neck area (47.4%) followed by the extremities (28.5%). AVMs are best characterized as being either focal or diffuse. Focal AVMs have good outcomes following adequate treatment. Diffuse lesions have multiple feeding vessel, which results in high rates of recurrence despite treatment. The management of AVMs includes conventional surgery and endovascular techniques. A combination of embolization and surgical resection has become the treatment of choice over the last years. The main goal of both forms of treatment being the complete blockage or resection of the nidus. Transcatheter embolization of vessels has evolved over the years and new embolic agents have emerged. The types of materials available for embolization are classified into mechanical devices, liquid agents and particulates. Efficacy, rate of recurrence and most common complications were evaluated. AVMs recurrence after embolization or resection is reported in up to 80% of cases. Incomplete resection and embolization can induce aggressive growth of the remaining nidus and the risk of progression is up to 50% within the first 5 years and recurrences can occur up to 10 years later. Although ethanol seems to be associated with the highest degree of cure and permanent occlusion, the overall complication rate reported was 48%. Other materials, such as cyanoacrylate, have obtained modest rates of complete remission, while the reported rates of complete regression of AVMs with Fibrin glue and Polyvinyl alcohol are above 50%. At present, there are no unified agreement on the ideal embolic agent. Therefore, a multidisciplinary approach is recommended to support decision making about the best therapeutic approach and to achieve optimal outcome. A long-term post-treatment follow-up is recommended to recognize early recurrence.

[Alcohol septal ablation for obstructive hypertrophic cardiomopathy]. / Alcoolisation septale dans la cardiomyopathie hypertrophique obstructive.

Alcohol septal ablation has become an attractive alternative to surgical myomectomy in symptomatic patients with obstructive hypertrophic cardiomyopathy. Its purpose is to achieve a therapeutic infarction in the sub-aortic territory responsible of the obstruction. It is indicated in symptomatic patients resistant to optimal medical treatment and having a left intraventricular gradient equal or higher than 50 mmHg, spontaneous or with exercise. The selection of candidates must be rigorous and the procedure must be performed in an experienced center, associating interventionalists and echocardiographists. Alcohol septal ablation is preferred in cases of favourable coronary anatomy, sub-aortic obstruction and absence of associated mitral valve defect. The septal alcohol technique is fast, effective and safe. The per-procedural contrast echocardiography helps identifying whether the myocardial segment is vascularized by the septal branch to be occluded. The benefits of alcohol septal ablation are comparable to those seen with surgical myectomy in terms of functional class, exercise capacity, and gradient regression. The morbidity and mortality observed in the short and mid terms are globally equivalent to that of the surgical intervention. The major complication is dominated by the occurrence of complete atrioventricular block requiring the implantation of a definitive pacemaker, a complication in sharp decline since the contrast ultrasound-guided technique has become widespread.

L'alcoolisation du septum par voie percutanée est devenue une alternative séduisante à l'intervention de myomectomie chirurgicale chez les patients symptomatiques porteurs d'une cardiomyopathie hypertrophique obstructive. Son but est de réaliser un infarctus thérapeutique dans le territoire septal basal responsable de l'obstruction. Elle est indiquée chez les patients symptomatiques, résistant au traitement médical optimal et présentant un gradient intraventriculaire gauche égal ou supérieur à 50 mmHg, spontané ou à l'effort. La sélection des candidats doit être rigoureuse et la procédure doit être confiée à un centre expérimenté, associant cardiologues interventionnels et échocardiographistes. L'alcoolisation septale est à privilégier en cas d'obstruction sous-aortique avec anatomie coronaire favorable et absence d'anomalie associée de l'appareil sous-valvulaire mitral. La technique d'alcoolisation septale est rapide, efficace et sûre. L'échocardiographie de contraste per-procédure permet aisément de repérer la branche septale à alcooliser. Les bénéfices de cette technique sont comparables à ceux observés avec la myectomie chirurgicale en termes de classe fonctionnelle, de capacité à l'effort et de régression du gradient. La morbi-mortalité observée, à court et moyen termes, est globalement équivalente à celle de l'intervention chirurgicale. La complication majeure est dominée par la survenue d'un bloc auriculo-ventriculaire complet nécessitant l'implantation d'un pacemaker définitif, complication en net recul depuis que la technique échoguidée s'est généralisée.

EUS-guided celiac ganglion radiofrequency ablation versus celiac plexus neurolysis for palliation of pain in pancreatic cancer: a randomized controlled trial (with videos).

BACKGROUND AND AIMS: Although EUS-guided celiac plexus neurolysis (EUS-CPN) is frequently performed, its efficacy for palliation of pain in pancreatic cancer is suboptimal. Recently, EUS-guided radiofrequency ablation (EUS-RFA) has been proposed as a palliative treatment option for pancreatic neoplasms. We performed a single-blind, randomized trial to compare the effectiveness of EUS-CPN and EUS-RFA for palliation of pain in pancreatic cancer. METHODS: Patients with abdominal pain because of locally advanced or metastatic pancreatic cancer underwent EUS-CPN (n = 14) or EUS-RFA (n = 12). EUS-RFA was performed using a 1F monopolar probe passed via a 19-gauge FNA needle, by targeting the area of celiac plexus or visualized ganglia. Primary outcome was pain severity as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire pancreatic cancer module (PAN26) administered pretreatment and at 2 and 4 weeks post-treatment. Secondary outcome measures were comparison of quality of life as determined by the PAN26 and EORTC Quality of Life Questionnaire core questionnaire (C30) and opioid analgesia use between the 2 groups. RESULTS: Both the PAN26 (49.0 vs 57.0, P < .001) and C30 (51.9 vs 64.4, P = .032) revealed less pain for EUS-RFA than for EUS-CPN. Also, the EUS-RFA cohort experienced significantly less-severe GI symptoms, were able to plan more for the future, and had better emotional functioning compared with the EUS-CPN group. CONCLUSIONS: Compared with EUS-CPN, EUS-RFA provided more pain relief and improved the quality of life for patients with pancreatic cancer. (Clinical trials registration number: NCT03152487.).

Choice of Septal Reduction Therapies and Alcohol Septal Ablation.

In patients with resting or provoked gradients and symptoms refractory to optimal medical therapy, alcohol septal ablation or surgical septal myectomy may be considered. Given the overall comparable outcomes after ablation and myectomy, there is, for many patients, equipoise between the two procedures. Septal ablation is performed with standard angioplasty guiding catheters, guidewires, and balloon catheters. In the Euro-ASA registry, NYHA functional class fell from 2.9 ± 0.5 to 1.6 ± 0.7 and gradient from 67 ± 36 to 16 ± 21 mm Hg at mean 3.9-year follow-up after septal ablation.

Aetiological spectrum, clinical differentiation and efficacy of polyethylene glycol over lactulose in children with constipation: Experience of 316 cases.

AIM: To find the aetiological spectrum, clinical features to differentiate organic from functional constipation (FC) and the efficacy of polyethylene glycol (PEG) over lactulose in the treatment of childhood constipation. METHODS: From January 2007 to December 2014, 316 consecutive children (up to 18 years) with constipation were included in this study. FC was defined as per Rome III criteria. Standard treatment protocol (disimpaction with PEG followed by laxatives) was followed in FC. Lactulose was used in the first 4 years of study and PEG in the last 4 years. Success of therapy was assessed at 3 months. RESULTS: The median age was 44 (25.00-78.00) months, and 227 (72%) were boys. The majority, 245 (77.5%), had FC, while Hirschsprung disease was the most common organic cause (39.4%). On multivariate analysis, delayed passage of meconium, growth failure, absence of retentive posturing and absent faecal impaction significantly (P < 0.05) determined an organic aetiology. In FC, successful outcome at 3 months was achieved equally with PEG and lactulose (81 vs. 76%, respectively). However, more children in lactulose group had to be switched over to PEG due to lack of efficacy (P = 0.0002). CONCLUSIONS: FC is the most common cause of constipation in children. Presence of delayed passage of meconium, growth failure and absence of retentive posturing and absent faecal impaction raise the suspicion of an organic cause. Both lactulose and PEG are equally effective. PEG has an edge over lactulose as the need for switch over was uncommon.