Functional genomics and metabolomics advance the ethnobotany of the Samoan traditional medicine "matalafi".

The leaf homogenate of Psychotria insularum is widely used in Samoan traditional medicine to treat inflammation associated with fever, body aches, swellings, wounds, elephantiasis, incontinence, skin infections, vomiting, respiratory infections, and abdominal distress. However, the bioactive components and underlying mechanisms of action are unknown. We used chemical genomic analyses in the model organism Saccharomyces cerevisiae (baker's yeast) to identify and characterize an iron homeostasis mechanism of action in the traditional medicine as an unfractionated entity to emulate its traditional use. Bioactivity-guided fractionation of the homogenate identified two flavonol glycosides, rutin and nicotiflorin, each binding iron in an ion-dependent molecular networking metabolomics analysis. Translating results to mammalian immune cells and traditional application, the iron chelator activity of the P. insularum homogenate or rutin decreased proinflammatory and enhanced anti-inflammatory cytokine responses in immune cells. Together, the synergistic power of combining traditional knowledge with chemical genomics, metabolomics, and bioassay-guided fractionation provided molecular insight into a relatively understudied Samoan traditional medicine and developed methodology to advance ethnobotany.

[THE VACCINATION CONTROVERSY IN THE JEWISH COMMUNITY IN LONDON IN THE LATE 19TH CENTURY: "NOTHING IS NEW UNDER THE SUN"].

INTRODUCTION: In the last decade of the 19th century, some hundred years after the introduction of the smallpox vaccine, a heated controversy broke out in London regarding the compulsory vaccination of children against the disease. Amongst those affected by the legislation, mandating the immunization of children against smallpox was a Jewish father who was eventually imprisoned for refusing to have his son vaccinated. His grounds for refusal were his religious beliefs and it is with his case and its aftermath that the present article is concerned. The two major protagonists in the controversy were Chief Rabbi of England, Dr. Herman Adler and Mr. J. H. Levi. According to the Chief Rabbi, members of the Anglo-Jewish community were required to comply with the law of the land and act in accordance with mainstream medical opinion regarding the vaccination of their children as a matter of their Jewish faith. Levi who was a prominent economist at London University and a champion of liberalism and individual freedom, strongly opposed the Chief Rabbi's ruling on Jewish as well as general grounds. The debate between the two protagonists as it emerges from newspaper clippings and articles of the period is similar in many ways to the contemporary vaccination controversy in both London and Israel. One salient feature of the 19th century debate is the failure of the health authorities to publish precise and ongoing reports on the importance and effectiveness of vaccination throughout the year and not only prior to anticipated outbreaks of the disease. One of the lessons to be learned from the present article is the need for the medical establishment to acquire expertise in the areas of communication and media in order to deal successfully with the phenomenon of vaccine refusal. Amongst the issues that would need to be confronted is that of the halakhic objections, if any, to compulsory vaccination, which is a central theme of this article.

[MEASLES VACCINATION IN CONTEMPORARY HALAKHAH].

INTRODUCTION: One of the features of the recent measles outbreak world-wide has been the resurgence of the opposition to vaccination in the religious Jewish community. The present article presents the positions of a broad spectrum of Orthodox rabbinical rulings ranging from Haredi to National Religious to Modern Orthodox on this issue. The overwhelming majority of the halakhic authorities cited are in favor of the vaccination of both adults and children. It is noteworthy that in their decisions the rabbis rely on mainstream medical expertise in relation to the threat to both individual and public health as a result of non-vaccination. They also demonstrate awareness of the arguments of those opposed to vaccination and find ways to refute them. Nevertheless, there are vaccinations such as the one against human papillomavirus infection that are not approved by many rabbis. In order to ensure adequate vaccination-induced immunity to highly infectious diseases in Israel it is vital that the medical community is aware of the normative halakhic position, and is able, if necessary, to explain it to the religious population. This need is even more pressing in the midst of the present COVID-19 pandemic, since the success of the vaccination program depends upon the voluntary cooperation of all sectors of the population, and statistically, the religious community would appear to have a comparatively higher infection rate than other groups.

[EPIDEMIOLOGICAL AND CLINICAL ASPECTS OF SMALLPOX IN THE LIGHT OF JEWISH SOURCES IN THE PERIOD PRIOR TO MODERN VACCINATION].

INTRODUCTION: Europe was affected by a particularly severe outbreak of smallpox during the 17th and 18th centuries. In the early 18th century, the use of vaccines began to spread. The vaccines in use at that time were not risk free, and both post-vaccine mortality and the risk of spreading the disease to the non-vaccinated population were a matter of public concern. The Jewish documents reviewed in this article present epidemiological and clinical information on smallpox among European Jewish communities in the last decades of the 18th century. These documents provide a useful tool for historical research in that they shed light on, and provide a source of information about the spread of the disease, and the various measures aimed at preventing its spread including vaccination, among Jewish communities at the time.

Novel role of the serine protease inhibitor elafin in gluten-related disorders.

OBJECTIVES: Elafin, an endogenous serine protease inhibitor, modulates colonic inflammation. We investigated the role of elafin in celiac disease (CD) using human small intestinal tissues and in vitro assays of gliadin deamidation. We also investigated the potential beneficial effects of elafin in a mouse model of gluten sensitivity. METHODS: Epithelial elafin expression in the small intestine of patients with active CD, treated CD, and controls without CD was determined by immunofluorescence. Interaction of elafin with human tissue transglutaminase-2 (TG-2) was investigated in vitro. The 33-mer peptide, a highly immunogenic gliadin peptide, was incubated with TG-2 and elafin at different concentrations. The degree of deamidation of the 33-mer peptide was analyzed by liquid chromatography-mass spectrometry. Elafin was delivered to the intestine of gluten-sensitive mice using a recombinant Lactococcus lactis vector. Small intestinal barrier function, inflammation, proteolytic activity, and zonula occludens-1 (ZO-1) expression were assessed. RESULTS: Elafin expression in the small intestinal epithelium was lower in patients with active CD compared with control patients. In vitro, elafin significantly slowed the kinetics of the deamidation of the 33-mer peptide to its more immunogenic form. Treatment of gluten-sensitive mice with elafin delivered by the L. lactis vector normalized inflammation, improved permeability, and maintained ZO-1 expression. CONCLUSIONS: The decreased elafin expression in the small intestine of patients with active CD, the reduction of 33-mer peptide deamidation by elafin, coupled to the barrier enhancing and anti-inflammatory effects observed in gluten-sensitive mice, suggest that this molecule may have pathophysiological and therapeutic importance in gluten-related disorders.

Exercise training increases the expression and nuclear localization of mRNA destabilizing proteins in skeletal muscle.

While a paucity of information exists regarding posttranscriptional mechanisms influencing mitochondrial biogenesis, in resting muscle the stability of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA has been linked to mitochondrial content. Therefore, in the current study we have examined whether exercise promotes mRNA accumulation through the induction of proteins affiliated with mRNA stabilization (human antigen R, HuR) or conversely by decreasing the expression of mRNA destabilizing proteins [AU-rich binding factor (AUF1) and CUG binding protein (CUG-BP1)]. A single bout of exercise increased (P < 0.05) the mRNA content of the transcriptional coactivator PGC-1α ∼3.5-fold without affecting mRNA content for HuR, CUG-BP1, or AUF1. One week of treadmill exercise training did not alter markers of mitochondrial content, the mRNA stabilizing protein HuR, or the mRNA destabilizing protein AUF1. In contrast, the mRNA destabilizing protein CUG-BP1 increased ∼40%. Four weeks of treadmill training increased the content of subunits of the electron transport chain ∼50%, suggesting induction of mitochondrial biogenesis. Expression levels for HuR and CUG-BP1 were not altered with chronic training; however, AUF1 expression was increased posttraining. Specifically, training increased (P < 0.05) total muscle expression of two of four AUF1 isoforms ∼50% (AUF1(p37), AUF1(p40)). Interestingly, these two isoforms were not detected in isolated nuclei; however, a large band representing the other two isoforms (AUF1(p42), AUF1(p45)) was present in nuclei and increased ∼35% following chronic training. Altogether the current data provides evidence that mitochondrial biogenesis occurs in the presence of increased CUG-BP1 and AUF1, suggesting that reductions in known mRNA destabilizing proteins likely does not contribute to exercise-induced mitochondrial biogenesis.

Natural cycles in South Pacific Gyre strength and the Southern Annular Mode.

The South Pacific Gyre (SPG) plays a vital role in regulating Southern Hemisphere climate and ecosystems. The SPG has been intensifying since the twentieth century due to changes in large scale wind forcing. These changes result from variability in the Southern Annular Mode (SAM), causing warming along the eastern SPG which affects local ecosystems. However, our understanding of SPG variability on timescales greater than several decades is poor due to limited observations. Marine sediment cores are traditionally used to determine if recent ocean trends are anomalous, but rarely capture centennial variability in the southwest Pacific and limit our understanding of SPG variability. Here we capture centennial SPG dynamics using a novel high-resolution paleocirculation archive: radiocarbon reservoir ages (R) and local reservoir corrections (∆R) in SPG deep-sea black corals. We find black coral R and ∆R correlates with SAM reconstructions over 0-1000 cal BP and 2000-3000 cal BP. We propose this correlation indicates varying transport of well-ventilated subtropical waters resulting from SPG and SAM interactions. We reconstruct several 'spin up' cycles reminiscent of the recent gyre intensification, which has been attributed to anthropogenic causes. This implies gyre strength and SAM show natural co-variability on anthropogenic timescales which should factor into future climate projections.

Mature teratoma within the posterior mediastinum.

Mature teratomas in the chest are typically located within the anterior mediastinum. The authors report a case of a mature teratoma in a young adult male with characteristic imaging features except for its location: the posterior mediastinum. On review of the literature, 3% to 8% are reported as confined to the posterior mediastinum and 13% have extension into other mediastinal compartments.

Traumatic aortic injury: an imaging review.

Traumatic aortic injury (TAI) is a major cause of fatality in high speed deceleration injuries. It accounts for 10-20% of fatalities in blunt chest trauma. These injuries are usually related to high-speed motor vehicle and motorcycle collisions, pedestrian-motor vehicle collisions, and falls. Only 10-20% of patients who suffer TAI survive the initial injury and reach the emergency department. If left untreated, 30% die within 6 h, 40-50% die within 24 h, and 90% die within 4 months. A chronic pseudoaneurysm will develop in 2-5% of patients whose injury is not diagnosed. It is imperative, therefore, that these injuries are detected promptly and accurately. Symptoms and physical examination findings are nonspecific. External evidence of chest wall injury is present in 7-90% of cases, so that in up to 30% of the cases no apparent chest injury is identified on physical examination. Chest radiographs are very sensitive in detecting mediastinal hemorrhage, but have a low positive predictive value for aortic injury. The positive predictive value for chest radiography ranges between 5% and 20% for TAI. Aortography has been considered the gold standard for many years in the evaluation of TAI, but is time-consuming, labor- and resource-intensive, and invasive. Because of the shortcomings of physical examination and these more traditional imaging examinations, computed tomography (CT) has become increasingly utilized as a screening and diagnostic tool. Recent investigations have documented its high sensitivity and specificity in the detection of TAI. This article reviews the recent investigations of imaging evaluation of TAI, with a focus on helical CT.