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Purpose – This article aims to understand where industry is in terms of digitalizing their operations, what features of this transformation are essential for practitioners, and what barriers they are facing during their journey. In addition, the authors aim to provide recommendations for organization to start their digital transformation. Design/methodology/approach – Through literature review, the authors summarize the emerging tools and technologies in operations and supply chains to inform the practitioners. Then, the authors use surveys conducted on 183 operations and supply chain professionals, and use statistical tools to examine the association between variables of the data set. The authors present real-life case studies to explain important steps of a digital transformation project. Findings – The survey results indicate that real-time monitoring and data analytics are viewed as the most important and needed tools for organizations. High cost, lack of stakeholder buy-in and lack of successful business use cases are major barriers for companies when starting a digital transformation. Practical implications – The authors provide recommendations for practitioners based on the survey responses, and outline that starting small, focusing on stakeholder buy-in and implementation of software are the three key steps for a successful transformation journey. Originality/value – Main contributions of this article are to understand practitioner perspectives in digitalization and provide guidelines for organizations to follow when transforming their operations. This research closes the gap between academic research and practice by collaborating with operations and supply chain professionals.

The fabrication and magnetization reversal mechanism of a self-aligned Ni/Ni80Fe20/Fe lateral heterostructure (LH) are presented. Using a combination of angled deposition and multiple selective etching processes, high quality LHs are successfully fabricated consisting of an array of bi-component dots made of a lens and a crescent of two different materials surrounded by antidot of a third material. Three materials, Ni, NiFe, and Fe, are combined in different orders to make the lens, crescent, and antidot. In isolated bi-component dots without the antidot matrix, the region with lower MS first undergoes a single-domain reversal followed by the vortex nucleation-annihilation reversals of the region with higher MS. In the LH, the antidot matrix interacts magnetostatically with the bi-component dots and modifies the switching fields, with the reversal process depending on which material forms the antidot. The fabrication technique and the tunable reversal process presented in this work are useful for designing functional magnetoelectronic devices. [ABSTRACT FROM AUTHOR]

Large-area arrays of magnetic Ni80Fe20 cylindrical nanoshells, nanocups, and perforated nanocups were synthesized using oblique deposition into topographical templates patterned using laser interference lithography. The geometry of the template and the tilt angle of the sample during deposition provide versatile control over the final geometry and dimension of nanostructures with thickness below 10 nm. Decreasing shell thickness led to a magnetization switching path between onion (bidomain) and reverse onion states, bypassing the vortex (flux-closed) state. The variation of magnetization reversal processes with geometry was characterized using vibrating sample magnetometry, and the results were in good agreement with micromagnetic simulations. [ABSTRACT FROM AUTHOR]

The magnetization reversal processes of rectangular and circular permalloy ring arrays are compared. Rectangular rings reverse via two different processes, one of which includes the formation of a vortex state. The corners of the rectangular rings affect domain wall pinning and reverse domain nucleation processes and alter the field values for the two major transitions between magnetic states as compared to a circular ring. The effects of film thickness are also investigated. Micromagnetic simulations are compared with the experiment results. [ABSTRACT FROM AUTHOR]

Abstract A few modes of perioperative local analgesia have been studied in order to reduce postoperative pain after laparoscopy, including preemptive local anesthetics in the trocar sites and intraperitoneal anesthetics administration at the end of the surgery. However, the evidence regarding their efficacy are conflicting. In addition, the combination of both aforementioned methods has been rarely studied. Our aim was to evaluate whether subcutaneous trocar site and/or intraperitoneal analgesia reduce pain after gynecologic operative laparoscopy. This was a single-centered, randomized, controlled, double-blinded trial. The patients were randomly assigned to one of four equally sized groups: group 1—subcutaneous and intraperitoneal analgesia; group 2—subcutaneous analgesia and intraperitoneal placebo; group 3—subcutaneous placebo and intraperitoneal analgesia; Group 4—subcutaneous and intraperitoneal placebo. The patients, the surgeons, and the pain evaluators were all blinded to the patient’s allocation. Included were patients who underwent elective operative laparoscopy. Exclusion criteria were: active infection, pregnancy, known sensitivity to Bupivacaine-Hydrochloride, chronic pelvic pain, surgeries with additional vaginal procedures, conversion to laparotomy, and malignancy. A total of 9 ml of Bupivacaine-Hydrochloride (Marcaine) 0.5%, or Sodium-Chloride 0.9%, as a placebo, were injected subcutaneously to the trocar sites (3 ml to each trocar site), prior to skin incision. In addition, 10 ml of Bupivacaine-Hydrochloride 0.5%, diluted with 40 ml of Sodium-Chloride 0.9% (a total of 50 ml solution), or 50 ml of Sodium-Chloride 0.9%, as a placebo, were injected intraperitoneally at the end of the surgery. By utilizing the 10 cm Visual-analogue-scale (VAS) we assessed post-operative pain at rest at 3, 8, and 24 h, and during ambulation at 8 and 24 h. The study was approved by the local Institutional Review Board and has been registered at clinicaltrials.gov. We conformed to the CONSORT recommendations. Between December 2016 and July 2019, a total of 119 patients were included in the study. Demographic and interventional characteristics were similar among the groups. The level of postoperative pain, either at rest or with change of position, was not significantly different between the groups, at all-time points. Application of subcutaneous and/or intraperitoneal analgesia is not effective in reducing pain after gynecologic operative laparoscopy. Clinical trial identification number: NCT02976571. Date of trial registration 11/29/2016. URL of the registration site: https://clinicaltrials.gov .

Photo by Hannah Busing on Unsplash INTRODUCTION Religion has long provided guidance that has led to standards reflected in some aspects of medical practices and traditions. The recent bioethical literature addresses numerous new problems posed by advancing medical technology and demonstrates an erosion of standards rooted in religion and long widely accepted as almost axiomatic. In the deep soul-searching that pervades the publications on bioethics, several disturbing and dangerous trends neglect some basic lessons of philosophy, logic, and history. The bioethics discourse on medical aid in dying emphasizes similarity over previously recognized important distinguishing features. For example, it overplays a likeness between assistance in dying and the withdrawal of life-saving technology. In many bioethics’ topics, arguments based on a logical continuum are used to question the lines demarcating important moral differences. l. The Line Between Ethical and Not: Logic Based on Continuum Careful case selection, often either end of a continuum, allows the tearing down or ridiculing of many rules and codes across most professions and fields of interest. This situation holds true for traffic laws as well as medical ethics guidelines. It is relatively simple for those who desire to attack a particular viewpoint by selecting a case that makes that position seem untenable. In the ethics realm, good and bad medicine exist at opposite ends of an ethical continuum, with many practices lying in between. For example, much of medical ethics exists between the Nazi criminal physicians and the most sainted nurse or physician. A gradual progression occurred over less than two decades from a utilitarian position that supported limited euthanasia for those with certain mental illnesses to genocide. German society embraced a utilitarian ethic in which the value of human life no longer was intrinsic but instrumental.[1] Many morally significant points on a continuum were then ignored as the misguided utilitarian policy rampantly continued. A point in the continuum to distinguish between ethically justifiable and that which is not can be difficult to identify compared to the two extremes. This continuum is not unique to ethics but can be applied to almost any other aspect of human life and endeavor. Between a severely ill schizophrenic person and a superbly well-adjusted individual, there is a continuum of mental and psychological function. The existence of a continuum should not paralyze thinking and prevent us from drawing lines and identifying moral differences based on objective criteria as well as moral philosophy. Yet, by focusing on a continuum, many bioethicists use logic to disregard dividing lines between an "ethical" and an "unethical" act. Unfortunately, sometimes bioethicists draw revolutionary conclusions that would change the scope of medical practices which is accepted as ethical. There are many examples of similar shifts on the continuum. Many authors argue for the ethical permissibility of abortion by pointing out that the human fetus is no different in various characteristics, one arguing it is as like an ape or chick as it is like a person,[2] and does not achieve unique human and individual characteristics until well into the first year of life.[3] While human fetuses arguably do not have certain distinctive qualities of personhood, most people shy away from the logical next conclusion: permitting infanticide. For example, Joshua Lederberg condemns infanticide, in the face of biological illogic, because of our emotional commitment to infants, to me, a relatively weak explanation. Sir Francis Crick suggests we might consider birth at two days of life in order to decide whether an infant is a "suitable" member of society.[4] Giublini and Minerva suggest that infanticide should be permissible since late pregnancy abortions are permissible, arguing there is no significant difference between a fetus just before birth and an infant just after birth.[5] Clearly the continuum approach would allow for subjective arguments in favor of later infanticide at other points many days post-birth. Years ago, with a cynical tone, I mentioned infanticide as a further step on the continuum beyond abortion, and I was rightly shouted down as being deliberately provocative to assert the logic would ever stretch so far. While it is not an accepted mainstream position, the movement in academic settings from widespread condemnation to limited possible acceptance of infanticide has taken place in an incredibly short time. Public opinion and medical opinion in these areas have shifted dramatically in a short time. In another area, from a biological and chemical point of view, there is a continuum from man down to a single carbon atom. Yet, it would not seem logical to ignore the emotional differences, the meaning of personhood, or the moral distinction between killing an insect and killing a person. ll. A False Continuum: Medical Aid in Dying I assert that there has been an erosion of ethical guidelines in recent years attributable to using continuums to camouflage important distinctions. James Rachels’ work on active and passive euthanasia, which contends that the two are ethically identical, exemplifies that logic.[6] He illustrates this thesis, using a continuum to compare different scenarios with like consequences as morally equivalent, by comparing the deliberate drowning of a child with a deliberate failure to rescue a drowning child when easily able to do so. The author's comparison proposes that since much of the medical profession has already made peace with withholding treatment in order to hasten death, consistency inexorably demands that we permit active euthanasia as well.[7] When permission for active euthanasia was first introduced, it was limited exclusively to patients suffering severely from an intractable, incurable, and irreversible disease. These guidelines have been continuously eroded. There is now a substantial serious consideration for permitting active euthanasia of healthy elderly individuals who feel that they have completed their lives and are "tired of living."[8] There are many moral and factual differences along the ethical continuum. In human life, there is a difference between a live baby and a fetus, between a viable fetus and one that is not, between a fetus and a zygote, and between a zygote and a sperm cell. Similarly, there is a difference between pulling a trigger to kill someone and not interfering in preventing his death, which is reprehensible though both may be. There is a difference between not resuscitating an 80-year-old man with cancer when his heart stops and injecting him with a fatal dose of potassium chloride. I argue that an overt act of taking life repels civilized human beings is to be commended and encouraged as the reverence for human life or even for just a moment of human life is one of the great contributions of our civilization. CONCLUSION As an orthodox Jew, I feel that divinely inspired guidelines that have stood the test of centuries shape my beliefs, and such guidelines contradict medical aid in dying. I cannot speak to the viewpoint of those who do not access religion in defining their moral stance, nor do I implicate them in the current bioethics' trends, as I am not aware of the personal role of religion in the lives of most such authors. While many nonreligious people have a firm philosophical grounding and oppose medical aid in dying, I suggest that in the absence of any religious or other absolute standards, developing logically defensible ethical guidelines may be challenging. At the least, religion may play a role in defining the points on the continuums that are ethically meaningful and refuting the trending beliefs that if the endpoint is the same, allowing different methods of arriving at that end are somehow ethically equal. The continuum of ways death may result does not negate analysis of whether death is brought about in ways that recognize the importance of life. The German philosopher Hans Jonas said, "It is a question whether without restoring the category of the sacred, the category most thoroughly destroyed by the scientific enlightenment, we can have an ethics able to cope with the extreme powers that we possess today and constantly increase and are compelled to use."[9] While countries vary on the role of religion in policy, with many emphasizing freedoms of religion, a recent position paper released by a group of Jewish, Christian, and Moslem leaders (the three Abrahamic religions) suggested the need for agreement on the unique sanctity of human life.[10] I would recommend that such a document serve as an example of consensus on critical foundational bioethical guidelines for democratic secular societies. - [1] Alexander L (1949) Medical science under dictatorship. New England Journal of Medicine, 241, p39-47 DOI10.1056/NEJM194907142410201 [2] Lederberg J. (1967) A geneticist looks at contraception and abortion, Annals of Internal Medicine 67, sup 2, 25-27. https:/doi.org/10.7326/0003-4819-67-3-25 [3] Ibid. [4] Editorial, Sociology: Logic of biology. Nature 220, 429 (1968) https://www.nature.com/articles/220429b0 [5] Giublini A Minerva F (2013) After-birth abortion: why should the baby live. J Med Ethics 39, 261- [6] Rachels J (1975) Active and passive euthanasia. New England Journal of Medicine 292, 78-80 [7] Ibid. [8] Cohen-Almagor R Euthanizing people who are "tired of life". in Euthanasia and Assisted Suicide-Lessons from Belgium. Ch 11 of Euthanasia and Assisted Suicide, Cambridge University Press pp173-187. 2017 and DOI; https://doi.org/10.1017/9781108182799.012 [9] Hans Jonas, Technology and Responsibility: Reflections on the New Tasks of Ethics, 1972, found as Chapter IX, Philosophical Essays, 1980. https://inters.org/jonas-technology-responsability [10] A position paper of the Abrahamic Monotheistic religions on matters concerning the end-of-life. Vatican Press 28 October 2019 https://press.vatican.va/content/salastampa/en/bollettino/pubblico/2019/10/28/191028f.html

A direct and systematic investigation of the magnetization dynamics in individual circular Ni80Fe20 disk of diameter (D) in the range from 300 nm to 1 µm measured using micro-focused Brillouin Light Scattering (μ-BLS) spectroscopy is presented. At high field, when the disks are in a single domain state, the resonance frequency of the uniform center mode is observed to reduce with reducing disk's diameter. For D = 300 nm, additional edge and end-domains resonant modes are observed due to size effects. At low field, when the disks are in a vortex state, a systematic increase of resonant frequency of magnetostatic modes in a vortex state with the square root of the disks' aspect ratio (thickness divided by radius) is observed. Such dependence diminishes for disks with larger aspect ratio due to an increasing exchange energy contribution. Micromagnetic simulations are in excellent agreement with the experiments. [ABSTRACT FROM AUTHOR]

Simultaneous vortex chirality and polarity control are observed in thickness-modulated [Co/Pd]n/Ti/Ni80Fe20 disks using magnetic force microscopy by applying a proper sequence of in-plane and out-of-plane reset fields. The thickness modulation in the NiFe layer introduces an additional shape anisotropy, which defines the vortex chirality during the in-plane reset field, while the [Co/Pd]n underlayer produces a large out-of-plane stray field, which stabilizes the vortex polarity in the NiFe layer. Micromagnetic simulations are compared with experiment results. [ABSTRACT FROM AUTHOR]

The effects of dipolar coupling on the static and dynamic behavior of coupled Ni80Fe20 dots in two lattice geometries have been systematically investigated as a function of film thickness t. For coupled two dots, a significant decrease in vortex nucleation and annihilation fields and a marked increase in ferromagnetic resonance (FMR) frequency were observed when compared with isolated dots of identical geometrical parameters. Interestingly, for t ≥ 50nm, when three dots are coupled along two orthogonal directions, two distinct FMR absorption peaks and a two-step switching of vortex annihilation were observed due to configurational anisotropy. Our experimental results are in good agreement with both the analytical and micromagnetic simulations. [ABSTRACT FROM AUTHOR]

A systematic investigation of the dynamic behavior of Ni80Fe20 ring arrays using broadband ferromagnetic resonance spectroscopy as a function of inter-ring spacing and ring thickness is presented. Four distinct resonance modes were found for rectangular rings compared to the two modes seen in circular rings of identical width due to the presence of sharp corners and nonuniform demagnetization field distribution. The resonance peaks were sensitive to the inter-ring spacing and the ring thickness due to magnetostatic coupling. Micromagnetic simulations and analytical calculations are compared with the experiment results. [ABSTRACT FROM AUTHOR]

Growth retardation and stress-induced premature plant senescence are accompanied by a severe yield reduction and raise a major agro-economic concern. To improve biomass and yield in agricultural crops under mild stress conditions, the survival must be changed to productivity mode. Our previous successful attempts to delay premature senescence and growth inhibition under abiotic stress conditions by autoregulation of cytokinins (CKs) levels constitute a generic technology toward the development of highly productive plants. Since this technology is based on the induction of CKs synthesis during the age-dependent senescence phase by a senescence-specific promoter (SARK), which is not necessarily regulated by abiotic stress conditions, we developed autoregulating transgenic plants expressing the IPT gene specifically under abiotic stress conditions. The Arabidopsis promoter of the stress-induced metallothionein gene (AtMT) was isolated, fused to the IPT gene and transformed into tobacco plants. The MT:IPT transgenic tobacco plants displayed comparable elevated biomass productivity and maintained growth under drought conditions. To decipher the role and the molecular mechanisms of CKs in reverting the survival transcriptional program to a sustainable plant growth program, we performed gene expression analysis of candidate stress-related genes and found unexpectedly clear downregulation in the CK-overproducing plants. We also investigated kinase activity after applying exogenous CKs to tobacco cell suspensions that were grown in salinity stress. In-gel kinase activity analysis demonstrated CK-dependent deactivation of several stress-related kinases including two of the MAPK components, SIPK and WIPK and the NtOSAK, a member of SnRK2 kinase family, a key component of the ABA signaling cascade. A comprehensive phosphoproteomics analysis of tobacco cells, treated with exogenous CKs under salinity-stress conditions indicated that >50% of the identified phosphoproteins involved in stress responses were dephosphorylated by CKs. We hypothesize that upregulation of CK levels under stress conditions desensitize stress signaling cues through deactivation of kinases that are normally activated under stress conditions. CK-dependent desensitization of environmental stimuli is suggested to attenuate various pathways of the avoidance syndrome including the characteristic growth arrest and the premature senescence while allowing normal growth and metabolic maintenance.

The magnetic vortex dynamics in thickness-modulated Ni80Fe20 disks in the form of a Ni80Fe20 lens on top of a Ni80Fe20 disk are investigated. The vortex core location can be systematically controlled via the geometry, and the propagation and annihilation can be detected using ferromagnetic resonance measurements. The thickness modulation provides an additional shape anisotropy, which defines the vortex chirality in the disk depending on the magnetization reversal history and the magnetic interactions between the disk and the lens. The vortex propagation and annihilation in each layer were identified by their resonance modes. [ABSTRACT FROM AUTHOR]

Obstetric anal sphincter injuries (OASIs) following vaginal deliveries are the main reason for subsequent development of anal incontinence in women. The diagnosis of such tears is crucial for treating and preventing such a grave sequela. The reported rate of OASIs in Israel was between 0.1% and 0.6%, out of all vaginal births, which is 10-fold lower than that reported in Europe and the United States. Structured hands-on training in repair of OASIs in seven medical centers in Israel significantly increased the detection rate of third-degree perineal tears. The implementation of such programs is crucial for increasing awareness and detection rates of OASIs following vaginal deliveries.

In nature, annual plants respond to abiotic stresses by activating a specific genetic program leading to early flowering and accelerated senescence. Although, in nature, this phenomenon supports survival under unfavorable environmental conditions, it may have negative agro-economic impacts on crop productivity. Overcoming this genetic programing by cytokinins (CK) has recently been shown in transgenic plants that overproduce CK. These transgenic plants displayed a significant increase in plant productivity under drought stress conditions. We investigated the role of CK in reverting the transcriptional program that is activated under abiotic stress conditions and allowing sustainable plant growth. We employed 2 complementary approaches: Ectopic overexpression of CK, and applying exogenous CK to detached Arabidopsis leaves. Transgenic Arabidopsis plants transformed with the isopentyltransferase (IPT) gene under the regulation of the senescence associated receptor kinase (SARK) promoter displayed a significant drought resistance. A transcriptomic analysis using RNA sequencing was performed to explore the response mechanisms under elevated CK levels during salinity stress. This analysis showed that under such stress, CK triggered transcriptional reprograming that resulted in attenuated stress-dependent inhibition of vegetative growth and delayed premature plant senescence. Our data suggest that elevated CK levels led to stress tolerance by retaining the expression of genes associated with plant growth and metabolism whose expression typically decreases under stress conditions. In conclusion, we hypothesize that CK allows sustainable plant growth under unfavorable environmental conditions by activating gene expression related to growth processes and by preventing the expression of genes related to the activation of premature senescence.

This paper presents the full debate held on October 1, 2014, which focused on the following resolution: “Publications which promote political agendas have no place in scientific and medical journals, and academics should refrain from publishing in such journals.” The debate moderator was Professor Shimon Glick. Taking the pro stance was Professor A. Mark Clarfield; the con stance was held by Professor Rael D. Strous. Following the first part of the debate, Dr Richard Horton, Editor-in-Chief of The Lancet, gave his thoughts on the topic. This was followed by the opportunity for rebuttal by Professors Clarfield and Strous. The debate was summarized and closed by Professor Glick. This paper provides a slightly edited text of the debate, for ease of reading.

We report the synthesis and characterization of a novel thiourea derivative of sphingomyelin (AD2765). In vitro assays using pure enzyme and/or cell extracts revealed that this compound inhibited the hydrolysis of BODIPY-conjugated or 14C-labeled sphingomyelin by acid sphingomyelinase and Mg2+-dependent neutral sphingomyelinase. Studies in normal human skin fibroblasts further revealed that AD2765 was taken up by cells and inhibited the hydrolysis of BODIPY-conjugated sphingomyelin in situ. In situ and in vitro studies also showed that this compound inhibited the synthesis of sphingomyelin from BODIPY-conjugated ceramide. The specificity of AD2765 for enzymes involved in sphingomyelin metabolism was demonstrated by the fact that it had no effect on the hydrolysis of BODIPY-conjugated ceramide by acid ceramidase or on the synthesis of BODIPY-conjugated glucosylceramide from BODIPY-conjugated ceramide. The overall effect of AD2765 on sphingomyelin metabolism was concentration-dependent, and treatment of normal human skin fibroblasts or cancer cells with this compound at concentrations > 10 μM led to an increase in cellular ceramide and cell death.Thus, AD2765 might be used to manipulate sphingomyelin metabolism in various ways, potentially to reduce substrate accumulation in cells from types A and B Niemann-Pick disease patients, and/or to affect the growth of human cancer cells.

BACKGROUND: Defensive medicine is the practice of diagnostic or therapeutic measures conducted primarily as a safeguard against possible malpractice liability. We studied the extent, reasons, and characteristics of defensive medicine in the Israeli health care system. METHODS AND FINDINGS: Cross-sectional study performed in the Israeli health care system between April and July 2008 in a sample (7%) of board certified physicians from eight medical disciplines (internal medicine, pediatrics, general surgery, family medicine, obstetrics and gynecology, orthopedic surgery, cardiology, and neurosurgery). A total of 889 physicians (7% of all Israeli board certified specialists) completed the survey. The majority [60%, (95%CI 0.57-0.63)] reported practicing defensive medicine; 40% (95%CI 0.37-0.43) consider every patient as a potential threat for a medical lawsuit; 25% (95%CI 0.22-0.28) have previously been sued at least once during their career. Independent predictors for practicing defensive medicine were surgical specialty [OR=1.6 (95%CI 1.2-2.2), p=0.0004], not performing a fellowship abroad [OR=1.5 (95%CI 1.1-2), p=0.027], and previous exposure to lawsuits [OR=2.4 (95%CI 1.7-3.4), p

The use of vaginal mesh in pelvic organ prolapse (POP) repair surgery has become more common in recent years. The purpose of the current study was to evaluate the common practice of Israeli urogynecologists, and to determine whether surgical practice has changed over the last two years. Methods. In 2009 and again in 2011, a survey was mailed to all urogynecologists affiliated with an academic institute in Israel. The survey consisted of 7 Likert-scale items and 3 open questions; the latter inquired about preferred type of surgery in three clinical scenarios. Results. Of 22 practitioners, 15 responded to the survey. The number of urogynecologists who reported using vaginal mesh for the repair of primary POP increased from 47 to 67% from 2009 to 2011. The number who would not use vaginal mesh in POP repair of elderly patients dropped from 60 to 3%. Finally, for the treatment of a 35-year-old patient with stage III uterine prolapse who desired to preserve fertility, 13% recommended the used vaginal mesh in 2009 compared with 47% in 2011. Conclusion. A survey of practitioners shows that the use of vaginal mesh for the repair of primary and recurrent pelvic organ prolapse has become more common among Israeli urogynecologists.

In spite of the enormous progress of Western medicine during the past century there has not be a concomitant rise in the public’s satisfaction with the medical profession. Much of the discontent relates to problems in physician–patient communication. The multiple advantages of good communication have been clearly demonstrated by numerous careful studies. While the past few decades have witnessed much more attention given to teaching communication skills in medical schools, there are a number of factors that create new problems in physician–patient communication and counteract the positive teaching efforts. The “hidden curriculum”, the increased emphasis on technology, the greater time pressures, and the introduction of the computer in the interface between physician and patient present new challenges for the teaching of physician-patient communication.

The Tomb of the Shroud is a first-century C.E. tomb discovered in Akeldama, Jerusalem, Israel that had been illegally entered and looted. The investigation of this tomb by an interdisciplinary team of researchers began in 2000. More than twenty stone ossuaries for collecting human bones were found, along with textiles from a burial shroud, hair and skeletal remains. The research presented here focuses on genetic analysis of the bioarchaeological remains from the tomb using mitochondrial DNA to examine familial relationships of the individuals within the tomb and molecular screening for the presence of disease. There are three mitochondrial haplotypes shared between a number of the remains analyzed suggesting a possible family tomb. There were two pathogens genetically detected within the collection of osteological samples, these were Mycobacterium tuberculosis and Mycobacterium leprae. The Tomb of the Shroud is one of very few examples of a preserved shrouded human burial and the only example of a plaster sealed loculus with remains genetically confirmed to have belonged to a shrouded male individual that suffered from tuberculosis and leprosy dating to the first-century C.E. This is the earliest case of leprosy with a confirmed date in which M. leprae DNA was detected.

Bioluminescence imaging (BLI) of luciferase reporters in small animal models offers an attractive approach to monitor regulation of gene expression, signal transduction, and protein-protein interactions, as well as following tumor progression, cell engraftment, infectious pathogens, and target-specific drug action. Conventional BLI can be repeated within the same animal after bolus reinjections of a bioluminescent substrate. However, intervals between image acquisitions are governed by substrate pharmacokinetics and excretion, therefore restricting temporal resolution of reinjection protocols to the order of hours, limiting analyses of processes in vivo with short time constants. To eliminate these constraints, we examined use of implanted micro-osmotic pumps for continuous, long-term delivery of bioluminescent substrates. Pump-assisted d -luciferin delivery enabled BLI for ⩾ 7 days from a variety of luciferase reporters. Pumps allowed direct repetitive imaging at < 5-minute intervals of the pharmacodynamics of proteasome- and IKK-inhibiting drugs in mice bearing tumors stably expressing ubiquitin-firefly luciferase or IκBα-firefly luciferase fusion reporters. Circadian oscillations in the olfactory bulbs of transgenic rats expressing firefly luciferase under the control of the period1 promoter also were temporally resolved over the course of several days. We conclude that implanted pumps provide reliable, prolonged substrate delivery for high temporal resolution BLI, traversing complications of repetitive substrate injections.

Protein Kinase A (PKA) neuronal function is controlled by the interaction of a regulatory (R) subunit dimer to two catalytic (C) subunits. Recently, the L50R variant in the gene encoding the RIβ subunit was identified in individuals with a novel neurodegenerative disease. However, the mechanisms driving the disease phenotype remained unknown. In this study, we generated a mouse model carrying the RIβ-L50R mutation to replicate the human disease phenotype and study its progression with age. We examined postmortem brains of affected individuals as well as live cell cultures. Employing biochemical assays, immunohistochemistry, and behavioral assessments, we investigated the impact of the mutation on PKA complex assembly, protein aggregation and neuronal degeneration. We reveal that RIβ is an aggregation-prone protein that progressively accumulates in wildtype and Alzheimer's mouse models with age, while aggregation is accelerated in the RIβ-L50R mouse model. We define RIβ-L50R as a causal mutation driving an age-dependent behavioral and disease phenotype in human and mouse models. Mechanistically, this mutation disrupts RIβ dimerization, leading to aggregation of its monomers. Intriguingly, interaction with the C-subunit protects the RIβ-L50R from self-aggregating, in a dose-dependent manner. Furthermore, cAMP signaling induces RIβ-L50R aggregation. The pathophysiological mechanism elucidated here for a newly recognized neurodegenerative disease, in which protein aggregation is the result of disrupted homodimerization, sheds light on a remarkably under-appreciated but potentially common mechanism across several neurodegenerative diseases., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

There have been reports of myocarditis following COVID-19 vaccination. We surveyed all hospitalized military personnel in the Isareli Defense Forces during the period of the COVID-19 vaccination operation (12/28/2021-3/7/2021) for diagnosed myocarditis. We identified 7 cases of myocarditis with symptoms starting in the first week after the second dose of COVID-19 Pfizer-BioNTech vaccine. One case of myocarditis diagnosed 10 days after the second dose of the vaccine was not included. These 8 cases comprise of all events of myocarditis diagnosed in military personnel during this time period. All patients were young and generally healthy. All had mild disease with no sequalae. The incidence of myocarditis in the week following a second dose of the vaccine was 5.07/100,000 people vaccinated. Due to the nature of this report no causality could be established. Clinicians should be aware of the possibility of myocarditis following Pfizer-BioNTech vaccination. True incidence rates should be further investigated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Remote ischemic preconditioning (RIPC) involves deliberate, brief interruptions of blood flow to increase the tolerance of distant critical organs to ischemia. This study tests the effects of limb RIPC in a porcine model of controlled hemorrhage without replacement therapy simulating an extreme field situation of delayed evacuation to definitive care. Twenty-eight pigs (47 ± 6 kg) were assigned to: (1) control, no procedure (n = 7); (2) HS = hemorrhagic shock (n = 13); and (3) RIPC + HS = remote ischemic preconditioning followed by hemorrhage (n = 8). The animals were observed for 7 h after bleeding without fluid replacement. Survival rate between animals of the RIPC + HS group and those of the HS group were similar (HS, 6 of 13[46%]-vs-RIPC + HS, 4 of 8[50%], p = 0.86 by Chi-square). Animals of the RIPC + HS group had faster recovery of mean arterial pressure and developed higher heart rates without complications. They also had less decrease in pH and bicarbonate, and the increase in lactate began later. Global oxygen delivery was higher, and tissue oxygen extraction ratio lower, in RIPC + HS animals. These improvements after RIPC in hemodynamic and metabolic status provide essential substrates for improved cellular response after hemorrhage and reduction of the likelihood of potentially catastrophic consequences of the accompanying ischemia.

Background: Hemorrhage is a leading cause of death on the battlefield. Current methods for predicting hemodynamic deterioration during hemorrhage are of limited accuracy and practicality. During a study of the effects of remote ischemic preconditioning in pigs that underwent hemorrhage, we noticed arrhythmias among all pigs that died before the end of the experiment but not among surviving pigs. The present study was designed to identify and characterize the early maladaptive hemodynamic responses (tachycardia in the presence of hypotension without a corresponding increase in cardiac index or mean arterial blood pressure) and their predictive power for early mortality in this experimental model., Methods: Controlled hemorrhagic shock was induced in 16 pigs. Hemodynamic parameters were monitored continuously for 7 h following bleeding. Changes in cardiovascular and laboratory parameters were analyzed and compared between those that had arrhythmia and those that did not., Results: All animals had similar changes in parameters until the end of the bleeding phase. Six animals developed arrhythmias and died early, while 10 had no arrhythmias and survived longer than 6 h or until euthanasia. Unlike survivors, those that died did not compensate for cardiac output (CO), diastolic blood pressure (DBP), and stroke volume (SV). Oxygen delivery (DO2) and mixed venous saturation (SvO2) remained low in animals that had arrhythmia, while achieving certain measures of recuperation in animals that did not. Serum lactate increased earlier and continued to rise in all animals that developed arrhythmias. No significant differences in hemoglobin concentrations were observed between groups., Conclusions: Despite similar initial changes in variables, we found that low CO, DBP, SV, DO2, SvO2, and high lactate are predictive of death in this animal model. The results of this experimental study suggest that maladaptive responses across a range of cardiovascular parameters that begin early after hemorrhage may be predictive of impending death, particularly in situations where early resuscitative treatment may be delayed.

Background: Tree-in-bud (TIB) is a radiologic pattern seen on high-resolution chest CT reflecting bronchiolar mucoid impaction occasionally with additional involvement of adjacent alveoli. Its microbiologic significance has not been systematically evaluated., Objectives: We aimed to establish the incidence of the TIB pattern as a proportion of all patients undergoing chest CT and to identify its etiology wherever possible., Methods: We included all patients with TIB pattern detected on chest CT in our institution from January 2007 to June 2012 and correlated this radiologic finding to the microbiologic etiology, which were available, for each patient., Results: During the study period, TIB pattern was described in 326 patients, which is 1.8% of all chest CTs. Of these, 220 (67.5%) patients had an infectious etiology and 34 (10.4%) had aspiration pneumonia. Other presumptive etiologies were in 13 (4%) lung malignancy, 31 (9.5%) other malignancies, 20 cases (6%) inconclusive etiology or incidental findings, and 8 (2.5%) had other inflammatory disorders. The relative incidence of the various organisms isolated reflected the overall incidence of these bacteria in community- or hospital-acquired populations independent of the TIB pattern. No correlation was found between distribution of TIB, the immune status, and the organism isolated., Conclusions: TIB pattern reflects endobronchiolar inflammation due mainly but not exclusively to an infectious cause. The microbiologic etiology in patients with this finding is similar to that of the general population (community acquired versus hospital acquired).

Glycosphingolipids, labeled with the fluorescent probe lissamine rhodamine were administered to skin fibroblasts in culture and were hydrolyzed in the intact cells to the corresponding lissamine rhodamine ceramide (N-acylsphingosine). This fluorescent ceramide was converted in the intact cells to the corresponding sphingomyelin which was secreted into the culture medium. In comparison, ceramide is not formed in cells derived from patients with lipid storage diseases, because of deficiencies in lysosomal glycolipid hydrolases. Consequently, fluorescent sphingomyelin was absent from the culture medium or present in considerably reduced quantities. This provided a procedure for diagnosing lipidoses, by analyzing the lissamine rhodamine sphingomyelin content in the culture medium, while maintaining the cells intact.