The effect of sulfoxo-bilactam-21-crown -7 on spermatogenesis in immature Balb/c mice

زمینه و هدف: کراون اترها ملکول های میزبان برای یون های فلزی و غیر فلزی هستند. توانایی کراون اترها در کنترل سیکل و تغییر فعالیت برخی از آنزیم ها گزارش شده است. در این مطالعه اثر یک کراون اتر جدید (سولفوکسو- بی لاکتام- 21- کراون-7) بر روی بافت بیضه و اسپرماتوژنز مورد بررسی قرار گرفته است. روش بررسی: در این مطالعه 24 سر موش نابالغ کوچک آزمایشگاهی (Balb/C) به سه گروه گروه کنترل (هیچ ماده ای دریافت نکردند)، شم )فقط توئین 80 دریافت کردند) و تجربی )سولفوکسو- بی لاکتام- 21- کراون-7 دریافت کردند) تقسیم شدند. Lethal dose 50 (LD50) دارو، به میزان 40 میلی گرم بر کیلوگرم تعیین شد. بر این اساس، دوز 20 میلی گرم بر کیلوگرم از این کراون اتر به روش درون صفاقی هر روز به مدت یک هفته به گروه تجربی تزریق شد. دو هفته پس از آخرین تزریق، حیوانات بیهوش شده و کشته شدند. خون جهت اندازه گیری هورمون از قلب گرفته شد. بافت بیضه، استخراج شد و جهت مطالعات بافت شناسی فیکس گردید. داده ها توسط آنالیز واریانس یکطرفه (ANOVA) و به دنبال آن تست توکی آنالیز شدند. یافته ها: تزریق درون صفاقی سولفوکسو- بی لاکتام- 21- کراون-7 (20 میلی گرم بر کیلوگرم) تغییر معنی داری در تعداد اسپرماتوگنی نوع A و B، اسپرماتوسیت اولیه و سلول های لیدیک در گروه تجربی در مقایسه با گروه کنترل و شم نشان نداد. افزایش هورمون جنسی مردانه، تستوسترون (001/0

A Straightforward Method to Produce Multi-Nanodrug Delivery Systems for Transdermal/Tympanic Patches Using Electrospinning and Electrospray

The delivery of drugs through the skin barrier at a predetermined rate is the aim of transdermal drug delivery systems (TDDSs). However, so far, TDDS has not fully attained its potential as an alternative to hypodermic injections and oral delivery. In this study, we presented a proof of concept of a dual drug-loaded patch made of nanoparticles (NPs) and ultrafine fibers fabricated by using one equipment, i.e., the electrospinning apparatus. Such NP/fiber systems can be useful to release drugs locally through the skin and the tympanic membrane. Briefly, dexamethasone (DEX)-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) fiber meshes were decorated with rhodamine (RHO)-loaded poly(lactic-co-glycolic acid) (PLGA) NPs, with RHO representing as a second drug model. By properly tuning the working parameters of electrospinning, DEX-loaded PHBHV fibers (i.e., by electrospinning mode) and RHO-loaded PLGA NPs (i.e., by electrospray mode) were successfully prepared and straightforwardly assembled to form a TDDS patch, which was characterized via Fourier transform infrared spectroscopy and dynamometry. The patch was then tested in vitro using human dermal fibroblasts (HDFs). The incorporation of DEX significantly reduced the fiber mesh stiffness. In vitro tests with showed that HDFs were viable for 8 days in contact with drug-loaded samples, and significant signs of cytotoxicity were not highlighted. Finally, thanks to a beaded structure of the fibers, a controlled release of DEX from the electrospun patch was obtained over 4 weeks, which may accomplish the therapeutic objective of a local, sustained and prolonged anti-inflammatory action of a TDDS, as is requested in chronic inflammatory conditions, and other pathological conditions, such as in sudden sensorineural hearing loss treatment

Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality among Patients with COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 � 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 �103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7) were included in the primary analysis (median interquartile range age, 62 50-71 years; 237 42.2% women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% 95% CI,-6.6% to 9.8%; odds ratio, 1.06 95% CI, 0.76-1.48; P =.70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% 1-sided 97.5% CI,-� to 3.4%; odds ratio, 1.83 1-sided 97.5% CI, 0.00-5.93), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% 95% CI, 0.4%-3.8%; P =.01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508. © 2021 American Medical Association. All rights reserved

Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study

Background: Many causes of vision impairment can be prevented or treated. With an ageing global population, the demands for eye health services are increasing. We estimated the prevalence and relative contribution of avoidable causes of blindness and vision impairment globally from 1990 to 2020. We aimed to compare the results with the World Health Assembly Global Action Plan (WHA GAP) target of a 25% global reduction from 2010 to 2019 in avoidable vision impairment, defined as cataract and undercorrected refractive error. Methods: We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. We fitted hierarchical models to estimate prevalence (with 95% uncertainty intervals [UIs]) of moderate and severe vision impairment (MSVI; presenting visual acuity from <6/18 to 3/60) and blindness (<3/60 or less than 10° visual field around central fixation) by cause, age, region, and year. Because of data sparsity at younger ages, our analysis focused on adults aged 50 years and older. Findings: Global crude prevalence of avoidable vision impairment and blindness in adults aged 50 years and older did not change between 2010 and 2019 (percentage change −0·2% [95% UI −1·5 to 1·0]; 2019 prevalence 9·58 cases per 1000 people [95% IU 8·51 to 10·8], 2010 prevalence 96·0 cases per 1000 people [86·0 to 107·0]). Age-standardised prevalence of avoidable blindness decreased by −15·4% [–16·8 to −14·3], while avoidable MSVI showed no change (0·5% [–0·8 to 1·6]). However, the number of cases increased for both avoidable blindness (10·8% [8·9 to 12·4]) and MSVI (31·5% [30·0 to 33·1]). The leading global causes of blindness in those aged 50 years and older in 2020 were cataract (15·2 million cases [9% IU 12·7–18·0]), followed by glaucoma (3·6 million cases [2·8–4·4]), undercorrected refractive error (2·3 million cases [1·8–2·8]), age-related macular degeneration (1·8 million cases [1·3–2·4]), and diabetic retinopathy (0·86 million cases [0·59–1·23]). Leading causes of MSVI were undercorrected refractive error (86·1 million cases [74·2–101·0]) and cataract (78·8 million cases [67·2–91·4]). Interpretation: Results suggest eye care services contributed to the observed reduction of age-standardised rates of avoidable blindness but not of MSVI, and that the target in an ageing global population was not reached. Funding: Brien Holden Vision Institute, Fondation Théa, The Fred Hollows Foundation, Bill & Melinda Gates Foundation, Lions Clubs International Foundation, Sightsavers International, and University of Heidelberg

Antibacterial Ag containing core-shell polyvinyl alcohol-poly (lactic acid) nanofibers for biomedical applications

Core-shell-structured polyvinyl alcohol (PVA)-poly (lactic acid) (PLA) nanofibers combining the hydrophilic trait of PVA and the biocompatibility of PLA were produced using coaxial electrospinning. This allowed the incorporation of AgNO3 in the PVA core of the distinct fibers as shown through transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) showed relatively uniform and bead-free fibers with smooth surfaces. Ag-containing fibers show significantly decreased diameters compared with Ag-free samples as a result of the increased conductivity of the spinning solutions with increasing amounts of AgNO3. In a postsynthetic treatment, the AgNO3 was reduced forming silver nanoparticles (Ag NPs). Ag NPs of 45 to 90 nm size were located in the PVA core but also on the surface of the core-shell fibers and as individual, agglomerated, and polymer-coated particles of 100-200 nm. Powder X-ray diffraction (PXRD), energy dispersive X-ray spectroscopy (EDX), and UV-vis absorption spectroscopy confirmed the increasing amounts of Ag in the core-shell fibers when using increasing amounts of AgNO3 in the spinning solutions. The antibacterial activity of the nanofiber mats against two prokaryotes Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) increased with increasing amounts of Ag, as expected and produces inhibition zones of 1 to 2 mm

Influence of dyeing conditions of natural dye extracted from Berberis integerrima fruit on color shade of woolen yarn

A new source of natural dye was introduced to obtain different colors on woolen yarn by varying the dyeing condition and formulation recipe. The fruit extract of Berberis integerrima was used as a natural dye for coloration of wool fibers. Response surface methodology (RSM) has been applied to design experimental runs to evaluate the interactive effects of the operating variables. The concentration of natural dye, concentration of mordant, pH of dye bath, and dyeing time at boiling temperature was selected as independent parameters. The effect of these parameters was examined on color shade (Hue angle) of dyed yarn samples as a dependent factor. The results were indicated that the different hue angles and color shades were achieved at proposed dyeing condition of wool fibers with B. integerrima which was in the range of 25° up to 282°. Extracted natural dye from B. integerrima was presented an inhibition zone at all applied concentrations and it was dependent on its concentration

Poly(lactic acid)-Based Electrospun Fibrous Structures for Biomedical Applications

Poly(lactic acid)(PLA) is an aliphatic polyester that can be derived from natural and renewable resources. Owing to favorable features, such as biocompatibility, biodegradability, good thermal and mechanical performance, and processability, PLA has been considered as one of the most promising biopolymers for biomedical applications. Particularly, electrospun PLA nanofibers with distinguishing characteristics, such as similarity to the extracellular matrix, large specific surface area and high porosity with small pore size and tunable mechanical properties for diverse applications, have recently given rise to advanced spillovers in the medical area. A variety of PLA-based nanofibrous structures have been explored for biomedical purposes, such as wound dressing, drug delivery systems, and tissue engineering scaffolds. This review highlights the recent advances in electrospinning of PLA-based structures for biomedical applications. It also gives a comprehensive discussion about the promising approaches suggested for optimizing the electrospun PLA nanofibrous structures towards the design of specific medical devices with appropriate physical, mechanical and biological functions

The influence of process parameters on the properties of electrospun PLLA yarns studied by the response surface methodology

Poly (L-lactide) (PLLA) fibrous yarns were prepared by electrospinning of polymer solutions in 2,2,2-trifluoroethanol. Applying spinning from two oppositely charged needles the spontaneous formed triangle of fibers at a grounded substrate could be assembled into fibrous yarns using a device consisting of a take-up roller and twister. The effect of processing parameters on the morphology, diameter and mechanical properties of PLLA yarns was investigated by the response surface methodology (RSM). This method allowed evaluating a quantitative relationship between polymer concentration, voltage, take-up rate and distance between the needles' center and the take-up unit on the properties of the electrospun fibers and yarns. It was found that at increasing concentrations up to 9 wt % uniform fibers were obtained with increasing mean diameters. Conversely, the fiber diameter decreased slightly when the applied voltage was increased. The take-up rate had a significant influence on the yarn diameter, which increased as the take-up rate decreased. The tensile strength and modulus of the yarns were correlated with these variables and it was found that the polymer concentration had the largest influence on the mechanical properties of the yarns. By applying the RSM, it was possible to obtain a relationship between processing parameters which are important in the fabrication of electrospun yarns

Self-Assembly-Driven Bi2S3 Nanobelts Integrated a Silk-Fibroin-Based 3D-Printed Aerogel-Based Scaffold with a Dual-Network Structure for Photothermal Bone Cancer Therapy

: Multifunctional all-in-one biomaterial combining the therapeutic and regeneration functionalities for successive tumor therapy and tissue regeneration is in high demand in interdisciplinary research. In this study, a three-dimensional (3D) aerogel-based composite scaffold with a dual-network structure generated through self-assembly and photo-cross-linking with combined properties of photothermally triggered controlled anticancer drug release and photothermal cancer cell ablation was successfully fabricated. The fabrication of composites consists of self-assembly of a silk fibroin methacrylate (SF-MA) biopolymer incorporated with hydrothermally driven bismuth sulfide (Bi2S3) methacrylate nanobelts, followed by a photo-cross-linking-assisted 3D-printing process. The developed scaffolds presented hierarchically organized porosity and excellent photothermal conversion thanks to the strong near-infrared (NIR) photon absorption of incorporated Bi2S3 nanobelts inside the scaffold matrix. The heat generated in the scaffold mediated by laser irradiation has not only triggered controlled and prolonged release of the anticancer drug but also significantly ablated the bone cancer cells adhered on the scaffold. In addition, the developed 3D composite scaffolds have demonstrated excellent biodegradability for organic and inorganic network constituents at different media, enabling them as potential implants to be replaced by de novo tissue. In combination of chemotherapy and photothermal therapy, the multifunctional 3D-printed composite aerogel scaffold is expected to be an excellent implantable material in bone tissue engineering (BTE) for successive cancer therapy and tissue regeneration