Search Results (7)

This article explores a story taken from the Talmud Bavli (Yevamot 65b) which describes a dialogue between the arguments raised by an anonymous woman and a rabbinical judge, R. Ammi, with regard to her demand for a divorce and for receipt of the payment for her prenuptial agreement. The article examines aspects relating to the design of the Talmudic story, which belongs to the genre of halakhic stories containing an argument, the law, and its explanation, i.e., elements that are not always explicitly stated in the Talmudic text. The article also examines the point of encounter between the pleas of the anonymous woman who sought a divorce from her husband alleged that he was infertile and that she wished to have a child, versus the strict customary legal halakhic law that exempted her from the religious obligation to procreate and therefore did not protect her rights. In addition, the article provides the context of the woman’s pleas in court and the attitudes of the judge towards the woman, as evident in two contradictory rulings with regard to the anonymous woman. Finally, the character of the anonymous woman, as reflected in the story, is described. This article joins a gradually developing trend in recent years within the study of the Talmud Bavli that addresses issues related to women’s status and gender discourse. Nevertheless, it is notable that different orientations emerged in the research with regard to gender issues from the mid-1990s onwards. Full article

Antibiotic resistance is a global health threat. There are a few antibiotics under development, and even fewer with new modes of action and no cross-resistance to established antibiotics. Accordingly, reformulation of old antibiotics to overcome resistance is attractive. Nano-mupirocin is a PEGylated nano-liposomal formulation of mupirocin, potentially enabling parenteral use in deep infections, as previously demonstrated in several animal models. Here, we describe extensive in vitro profiling of mupirocin and Nano-mupirocin and correlate the resulting MIC data with the pharmacokinetic profiles seen for Nano-mupirocin in a rat model. Nano-mupirocin showed no cross-resistance with other antibiotics and retained full activity against vancomycin-, daptomycin-, linezolid- and methicillin- resistant Staphylococcus aureus, against vancomycin-resistant Enterococcus faecium, and cephalosporin-resistant Neisseria gonorrhoeae. Following Nano-mupirocin injection to rats, plasma levels greatly exceeded relevant MICs for >24 h, and a biodistribution study in mice showed that mupirocin concentrations in vaginal secretions greatly exceeded the MIC₉₀ for N. gonorrhoeae (0.03 µg/mL) for >24 h. In summary, Nano-mupirocin has excellent potential for treatment of several infection types involving multiresistant bacteria. It has the concomitant benefits from utilizing an established antibiotic and liposomes of the same size and lipid composition as Doxil^®, an anticancer drug product now used for the treatment of over 700,000 patients globally. Full article

The understanding that systemic context and tissue crosstalk are essential keys for bridging the gap between in vitro models and in vivo conditions led to a growing effort in the last decade to develop advanced multi-organ-on-a-chip devices. However, many of the proposed devices have failed to implement the means to allow for conditions tailored to each organ individually, a crucial aspect in cell functionality. Here, we present two 3D-print-based fabrication methods for a generic multi-organ-on-a-chip device: One with a PDMS microfluidic core unit and one based on 3D-printed units. The device was designed for culturing different tissues in separate compartments by integrating individual pairs of inlets and outlets, thus enabling tissue-specific perfusion rates that facilitate the generation of individual tissue-adapted perfusion profiles. The device allowed tissue crosstalk using microchannel configuration and permeable membranes used as barriers between individual cell culture compartments. Computational fluid dynamics (CFD) simulation confirmed the capability to generate significant differences in shear stress between the two individual culture compartments, each with a selective shear force. In addition, we provide preliminary findings that indicate the feasibility for biological compatibility for cell culture and long-term incubation in 3D-printed wells. Finally, we offer a cost-effective, accessible protocol enabling the design and fabrication of advanced multi-organ-on-a-chip devices. Full article

We previously reported the development of a novel formulation of an ultra-long-acting local anesthetic based on bupivacaine encapsulated in large multivesicular liposomes (Bupisomes) embedded in hydrogel. This formulation (Bupigel) prolonged bupivacaine release from the formulation in dissolution-like studies in vitro and analgesia in vivo in mouse, rat, and pig models. In this study we assessed Bupigel neurotoxicity on rabbit sciatic nerve using histopathology and electrophysiologic testing. Sciatic nerves of both hind limbs were injected dropwise with different formulations. Nerve conduction studies and needle electromyography two weeks after perineural administration showed signs of neural damage after injection of free lidocaine and bupivacaine, while there was no sign of neural damage after injection with saline, demonstrating the validity of the method. This test also did not show evidence of motor or sensory nerve damage after injection with liposomal bupivacaine at a dose 10-times higher than free bupivacaine. Histologically, signs of neural damage could be observed with lidocaine. Nerves injected with Bupigel showed mild signs of inflammation and small residues of hydrogel in granulomas, indicating a long residence time of the hydrogel at the site of injection, but no histopathological signs of nerve damage. This demonstrated that early signs of neural damage were detected electrophysiologically, showing the usefulness and sensitivity of electrodiagnostic testing in detection of neural damage from new formulations. Full article

This article refers to a Cairo Genizah fragment related to Bavli, Tractate Eruvin 102b-104a, identified as Cambridge, UL T-S F2 (2) 23. FGP No. C 98948. In the fragment, there are two words, “mor” and “yabolet”, which were written as vocalized by the scribe or copyist. Their pronunciation differs from that customary today, i.e., “mar” and “yabelet”. The purpose of this paper is to explain how this pronunciation was generated, the evolvement and development of this pronunciation as it appears in the fragment, and to examine whether there are additional words in other sources that were pronounced similarly. This paper begins with a description of the Genizah fragment and continues with a reproduction of the fragment itself. Full article

PEGylated nanomedicines are known to induce infusion reactions (IRs) that in some cases can be life-threatening. Herein, we report a case study in which a patient with rare mediastinal and intracardiac IgG4-related sclerosing disease received 8 treatments of intravenously administered PEGylated liposomal methylprednisolone-succinate (NSSL-MPS). Due to the ethical requirements to reduce IRs, the patient received a cocktail of premedication including low dose of steroids, acetaminophen and H2 blockers before each infusion. The treatment was well-tolerated in that IRs, complement activation, anti-PEG antibodies and accelerated blood clearance of the PEGylated drug were not detected. Prior to the clinical study, an in vitro panel of assays utilizing blood of healthy donors was used to determine the potential of a PEGylated drug to activate complement system, elicit pro-inflammatory cytokines, damage erythrocytes and affect various components of the blood coagulation system. The overall findings of the in vitro panel were negative and correlated with the results observed in the clinical phase. Full article

The paper introduces the tripartite structure used to shape principles of halachah. The unique design is expressed in a formal style consisting of three statements made by different sages, where each statement contains three halachic principles that have been grouped together in one place in the passage. The design of the halachic principles using a tripartite structure also clarifies the absence of additional halachic rules and the lack of material discussion of the halachah principles brought in the passage. The aim and the importance of this article is in presenting the design of halachic principles in the form of a tripartite structure, as well as how this pattern emerged and the special style of its appearance in the passage. Full article