Public health is connected to cannabis with regard to food, animal feed (feed), and pharmaceuticals. There¬fore, the use of phytocannabinoids should be examined from a One Health perspective. Current knowledge on medical cannabis treatment (MCT) does not address sufficiently diseases which are of epidemiological and of zoonotic concern. The use of cannabinoids in veterinary medicine is illegal in most countries, mostly due to lack of evidence-based medicine. To answer the growing need of scientific evidence-based applicable medicine in both human and veterinary medicine, a new approach for the investigation of the therapeutic potential of cannabinoids must be adopted. A model that offers direct study of a specific disease in human and veterinary patients may facilitate development of novel therapies. Therefore, we urge the regulatory authorities—the ministries of health and agriculture (in Israel and worldwide)—to publish guidelines for veterinary use due to its importance to public health, as well as to promote One Health-related preclinical translational medicine studies for the general public health.
Background: There is a consensus among the halachic authorities that life-saving actions override Sabbath prohibitions. They are painstaking in securing that the sanctity of the Sabbath is maintained but that not a single life be lost.
Objective: This manuscript examines if and when a relative’s presence at the bedside of a seriously ill individual is potentially life-saving against the backdrop of the scientific literature. It specifically addresses the permissibility of traveling in a motorized vehicle, generally prohibited on the Sabbath, to be with one’s relative in hospital for the provision of emotional support.
Methods: Discourse of the halachic issues in the context of the scientific literature.
Results: Stress, mental or physical, has been determined as a potentially life-threatening condition in many disease entities. The literature attests to both the patient’s and the professionals’ perception of the curative potential of the presence of loved ones by advocating for the patient and relieving stress in the hospital experience. Emotional support from a loved one is perceived by some patients as vital to survival. There is halachic consensus that a patient’s perception of the emotional need for a relative’s presence is sufficient to permit overriding rabbinic prohibitions. Torah prohibitions, which may be overridden for medical needs, may be overridden for emotional support, providing a health professional or family member attests to the fulfilment of this specific need as diminishing the danger to the patient’s life. In certain cases, the latter contingency is unnecessary.
Conclusions: Emotional support has an impact on the patient’s health status; the degree to which its impact is strong enough to save life is still being studied. As more data from scientific studies emerge, they may be relevant to sharpening the halachic rulings with respect to the issue at hand.
Anti-citrullinated protein antibodies (ACPAs) are highly specific serologic markers for rheumatoid arthritis (RA) and can pre-date clinical disease onset by up to 10 years, also predicting erosive disease. The process of citrullination, the post-translational conversion of arginine to citrulline residues, is mediated by peptidylarginine deiminase (PAD) enzymes present in polymorphonuclear cells (PMNs). Calcium ions (Ca2+) are required for PAD activation, but the intracellular Ca2+ concentration in normal cells is much lower than the optimal Ca2+ concentration needed for PAD activation. For this reason, it has been proposed that PAD activation, and thus citrullination, occurs only during PMN cell death when PAD enzymes leak out of the cells into the extracellular matrix, or extracellular Ca2+ enters the cells, with the high Ca2+ concentration activating PAD. Recently, using artificial in vitro systems to corroborate their hypothesis, Romero et al. demonstrated that “hypercitrullination,” citrullination of multiple intracellular proteins, occurs within synovial fluid (SF) cells of RA patients, and that only modes of death leading to membranolysis such as perforin-granzyme pathway or complement membrane attack complex activation cause hypercitrullination. In order for Romero’s hypothesis to hold, it is reasonable to surmise that PMN-directed lysis should occur in the rheumatoid joint or the circulation of RA patients. Research conducted thus far has shown that immunoglobulin G (IgG) targeting PMNs are present in RA SF and mediate PMN activation. However, the role of anti-PMN IgG in mediating complement activation and subsequent PMN lysis and hypercitrullination has not been fully evaluated.
Anti-citrullinated protein autoantibodies (ACPAs) are the major autoantibodies in rheumatoid arthritis (RA). Anti-citrullinated protein autoantibodies are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. Presence of ACPA is associated with joint damage and extra-articular manifestations, suggesting that ACPAs are most likely pathogenic autoantibodies in RA. In vitro, ACPAs induce macrophage tumor necrosis factor alpha (TNF-α) production, osteoclastogenesis, and complement activation. These autoantibodies also induce the formation of neutrophil extracellular traps (NETs). Additionally, ACPAs induce pathogenic cytokines expression and oxidative stress in immune cells derived from RA patients. The aim of this review is to show the pathogenic roles of these autoantibodies in RA.
Background: The PROSPECT (Procedure-Specific Postoperative Pain Management) Group recommended a single injection femoral nerve block in 2008 as a guideline for analgesia after total knee arthroplasty. Other authors have recommended the addition of sciatic and obturator nerve blocks. The lateral femoral cutaneous nerve is also involved in pain syndrome following total knee arthroplasty. We hypothesized that preoperative blocking of all four nerves would offer superior analgesia to femoral nerve block alone.
Methods: This is a prospective, randomized, controlled, and observer-blinded clinical study. A total of 107 patients were randomly assigned to one of three groups: a femoral nerve block group, a multiple nerve block group, and a control group. All patients were treated postoperatively using patient-controlled intravenous analgesia with morphine. Pain intensity at rest, during flexion and extension, and morphine consumption were compared between groups over three days.
Results: A total of 90 patients completed the study protocol. Patients who received multiple nerve blocks experienced superior analgesia and had reduced morphine consumption during the postoperative period compared to the other two groups. Pain intensity during flexion was significantly lower in the “blocks” groups versus the control group. Morphine consumption was significantly higher in the control group.
Conclusions: Pain relief after total knee arthroplasty immediately after surgery and on the first postoperative day was significantly superior in patients who received multiple blocks preoperatively, with morphine consumption significantly lower during this period. A preoperative femoral nerve block alone produced partial and insufficient analgesia immediately after surgery and on the first postoperative day. (Clinical trial registration number (NIH): NCT01303120)
Osteoporosis is a common condition with significant health care costs. First-line therapy is with bisphosphonates, which have proven anti-fracture efficacy. Around 10 years after the introduction of bisphosphonates reports began to be published of atypical femoral fractures (AFFs) that may be associated with this therapy. These fractures are associated with significant morbidity although lower mortality than the more common osteoporotic neck-of-femur fractures. A case definition has been described to allow identification of this class of fracture. Further work has established a high relative risk of AFFs in patients treated with bisphosphonates, but a low absolute risk in comparison to that of osteoporotic fractures. Proposed pathological mechanisms include low bone turnover states leading to stress/insufficiency fractures. Clinicians should be aware of the risk of AFFs and in particular the high rate of prodromal thigh/groin pain that warrants investigation in a patient receiving a bisphosphonate. If an incomplete fracture is diagnosed then bisphosphonate therapy needs to be stopped and prophylactic surgery may be considered. Due to these rare side effects patients on bisphosphonates require regular review, and this is particularly advised after 5 years of oral or 3 years of intravenous therapy.
The advent of sophisticated diagnostics has enabled the discovery of previously unknown arthropod-borne viruses like Chikungunya. This infection has become increasingly prevalent in the last 10 years across the Indian Ocean and has been brought to media attention by a recent outbreak in the Caribbean. The outbreak has been aided by a drastic rise in air travel, allowing infected individuals to transport the virus to pre¬viously unaffected regions. In addition, a recently documented viral mutation has allowed its transmission by the Aedes albopictus mosquito, therefore facilitating outbreaks in Southern Europe and the USA. The duration and extent of the arthritis seen peri- and post infection has become a topic of academic interest. Although published data are largely observational, there has been a definite increase in original research focusing on this. Symptoms can persist for years, particularly in older patients with pre-existing medical conditions. The etiology is still not fully understood, but viral persistence and immune activation within synovial fluid have been shown in mouse models. There have been no prospective clinical trials of treatment in humans; however, animal trials are in process. The mainstay of treatment remains anti-inflammatories and steroids where necessary. The clinical presentation seems to mimic common rheumatological conditions like rheumatoid arthritis; therefore recent recommendations suggest the use disease-modifying agents as a common practice for the specific syndrome. This review uses recent published data and draws on our own clinical experience to provide an overview of joint complications of Chikungunya infection.
Inflammation induced by toxins, micro-organisms, or autoimmunity may result in pathogenic fibrosis, leading to long-term tissue dysfunction, morbidity, and mortality. Immune cells play a role in both induction and resolution of fibrosis. γδ T cells are an important group of unconventional T cells characterized by their expression of non-major histocompatibility complex restricted clonotypic T cell receptors for non-peptide antigens. Accumulating evidence suggests that subsets of γδ T cells in experimentally induced fibrosis following bleomycin treatment, or infection with Bacillus subtilis, play pro-inflammatory roles that instigate fibrosis, whereas the same cells may also play a role in resolving fibrosis. These processes appear to be linked at least in part to the cytokines produced by the cells at various stages, with interleukin (IL)-17 playing a central role in the inflammatory phase driving fibrosis, but later secretion of IL-22, interferon γ, and CXCL10 preventing pathologic fibrosis. Moreover, γδ T cells appear to be involved, in an antigen-driven manner, in the prototypic human fibrotic disease, systemic sclerosis (SSc). In this paper we review in brief the scientific publications that have implicated γδ T cells in fibrotic diseases and their pro- and anti-fibrotic effects.
Neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) is a complex condition that remains poorly understood, and includes heterogeneous manifestations involving both the central and peripheral nervous system, with disabling effects. There are several models to improve NPSLE diagnosis when a neurological syndrome is present. In the last couple of years, the growing knowledge of the role of cytokines and antibodies in NPSLE, as well as the development of new functional imaging techniques, has brought some insights into the physiopathology of the disease, but their validation for clinical use remains undetermined. Furthermore, besides the classic clinical approach, a new tool for screening the 19 NPSLE syndromes has also been developed. Regarding NPSLE therapeutics, there is still no evidence-based treatment approach, but some data support the safety of biological medication when classic treatment fails. Despite the tendency to reclassify SLE patients in clinical and immunological subsets, we hope that these data will inspire medical professionals to approach NPSLE in a manner more tailored to the individual patient.
Background: Fever is a source of considerable parental anxiety. Numerous studies have also confirmed similar anxiety among health care workers. This study analyzed caregiver knowledge of fever, and beliefs concerning children with a febrile illness, with an emphasis on the referring physician.
Methods: This was a cross-sectional study of 100 caregivers of children 3 months to 12 years old, treated at an urban tertiary care pediatric emergency department for fever. Caregiver knowledge was assessed with a questionnaire.
Results: Most caregivers correctly defined the threshold for fever as >38.0–38.3°C. Caregivers commonly believed that fever can cause brain damage and epilepsy; the frequency of this belief was not affected by whether they were referred to the emergency department by their pediatrician/family physician or by another physician or arrived without a referral. For a comfortable-appearing child with a temperature not above 38.0°C, both groups reported that they would give antipyretics in similar proportions (mean 31%). The majority of parents in both groups believed that teething could cause fever (mean 74%).
Conclusion: Caregivers in this study had limited knowledge of fever and its management in children, even if referred by their primary care physician. We suggest that there is a need for aggressive educational interventions to reduce parents’ fever phobia, in clinics as well as in pediatric emergency departments, and that this need may extend to the education of medical personnel as well.
