Compounding vulnerabilities: Syndemics and the social determinants of disease in the past

Objective: This article explores the theory and utility of a syndemic approach for the study of disease in the past. Syndemic principles are examined alongside other theoretical developments within bioarchaeology. Two case studies are provided to illustrate the efficacy of this approach: Tuberculosis and vitamin D deficiency in 18th and 19th century England, and malaria and helminth infections in Early Medieval England. Materials: Public health studies of present syndemics, in addition to published bioarchaeological, clinical and social information relating to the chosen case studies. Methods: The data from these two historical examples are revisited within a syndemic framework to draw deeper conclusions about disease clustering and heterogeneity in the past. Results: A syndemic framework can be applied to past contexts using clinical studies of diseases in a modern context and relevant paleopathological, archaeological, and historical data. Conclusions: This approach provides a means for providing a deeper, contextualised understanding ancient diseases, and integrates well with extant theoretical tools in bioarchaeology Significance: Syndemics provides scholars a deep-time perspective on diseases that still impact modern populations. Limitations: Many of the variables essential for a truly syndemic approach cannot be obtained from current archaeological, bioarchaeological, or historical methods. Suggestions for further research: More detailed and in-depth analysis of specific disease clusters within the past and the present, which draws on a comprehensive analysis of the social determinants of health

Sensing the Dead: Mortuary Ritual and Tomb Visitation at Nabataean Petra

The visual prominence of mortuary structures within the Nabataean capital city of Petra clearly indicates that the deceased maintained a constant presence amongst the living. However, current systematic archaeological exploration of these mortuary features documents a more intimate view of the interaction between the living and the dead. Since 1998, the Petra North Ridge Project has sought to record the mortuary practices and gather data on health and diet of non-elite residents of 1st cent. ad Petra. Artifactual, taphonomic, and osteological data indicate that engagement of the city’s inhabitants with the dead occurred through the senses of smell, touch, taste, and sight. Nabataean visits to their familial tombs included ritual feasting and reorganization of the mortuary space, accompanied by the scents of incense, perfumed oils, and quicklime. In addition, mourners left behind material goods that served to illuminate, bedazzle, and entertain the dead. Through this repeated exchange of sensory stimulation, the Nabataeans established and preserved a dynamic relationship with their deceased ancestors.La prééminence visuelle des bâtiments funéraires dans la capitale nabatéenne de Pétra indique clairement que les défunts demeuraient constamment présents parmi les vivants. L'exploration archéologique actuellement menée de façon systématique sur les structures funéraires permet cependant d’apporter une vision plus intime de l'interaction entre les vivants et les morts. Depuis 1998, le Petra North Ridge Project cherche à documenter les pratiques funéraires et à recueillir des données sur la santé et l'alimentation des résidents du ier s. apr. J.-C. à Pétra n’ayant pas appartenu à l’élite. Les données artefactuelles, taphonomiques et ostéologiques indiquent que la relation des habitants de la ville avec leurs défunts passait par l'odorat, le toucher, le goût et la vue. Les visites des Nabatéens à leurs tombes familiales incluaient un festin rituel ainsi que la réorganisation de l'espace funéraire, accompagnés par des odeurs d'encens, d'huiles parfumées et de chaux vive. En outre, les proches du défunt ont laissé derrière eux des biens matériels qui servaient à éclairer, à impressionner et à divertir les morts. À travers cet échange répété de stimulation sensorielle, les Nabatéens établissaient et conservaient une relation dynamique avec leurs ancêtres décédés.ملخص – يشير البروز البصري للمباني الجنائزية في عاصمة المملكة النبطية البتراء بوضوح إلى أن المتوفين كانوا يظلون حاضرين باستمرار بين الأحياء; غير أن الاستكشاف الأثري الذي يجري حالياً بصورة منتظمة على المباني الجنائزية يتيح رؤية أكثر حميمية للتفاعل بين الأحياء والأموات. منذ عام ١٩٩٨, يسعى مشروع حافة البتراء الشمالية (Petra North Ridge Project) إلى توثيق الممارسات الجنائزية, وإلى جمع معطيات عن صحة وتغذية سكان القرن الأول الميلادي في البتراء، والذين لم يكونوا ينتمون إلى النخبة. وتشير البيانات المتعلقة باللقى الأثرية, وبحالة الجثث بعد الدفن (تافونوميك), والعظامية إلى أن علاقة سكان المدينة مع المتوفين كانت تمر بالشم, باللمس, بالذوق وبالبصر. اشتملت زيارات الأنباط إلى قبورهم العائلية على وليمة شعائرية بالإضافة إلى إعادة تنظيم الحيز الجنائزي، مصحوبين بروائح البخور والزيوت المعطرة والكلس الحي. وبالإضافة إلى ذلك, ترك أقارب المتوفى وراءهم ممتلكات مادية تفيد بتنوير وإثارة إعجاب وتسلية الموتى. من خلال هذا التبادل المتكرر للإثارة الحسية, أنشأ الأنباط وحافظوا على علاقة ديناميكية مع أسلافهم المتوفين

Bacterial defenses against a natural antibiotic promote collateral resilience to clinical antibiotics

As antibiotic-resistant infections become increasingly prevalent worldwide, understanding the factors that lead to antimicrobial treatment failure is essential to optimizing the use of existing drugs. Opportunistic human pathogens in particular typically exhibit high levels of intrinsic antibiotic resistance and tolerance1, leading to chronic infections that can be nearly impossible to eradicate2. We asked whether the recalcitrance of these organisms to antibiotic treatment could be driven in part by their evolutionary history as environmental microbes, which frequently produce or encounter natural antibiotics3,4. Using the opportunistic pathogen Pseudomonas aeruginosa as a model, we demonstrate that the self-produced natural antibiotic pyocyanin (PYO) activates bacterial defenses that confer collateral tolerance to certain synthetic antibiotics, including in a clinically-relevant growth medium. Non-PYO-producing opportunistic pathogens isolated from lung infections similarly display increased antibiotic tolerance when they are co-cultured with PYO-producing P. aeruginosa. Furthermore, we show that beyond promoting bacterial survival in the presence of antibiotics, PYO can increase the apparent rate of mutation to antibiotic resistance by up to two orders of magnitude. Our work thus suggests that bacterial production of natural antibiotics in infections could play an important role in modulating not only the immediate efficacy of clinical antibiotics, but also the rate at which antibiotic resistance arises in multispecies bacterial communities

Environmental exposure to polychlorinated biphenyls and p,p\u27-DDE and sperm sex-chromosome disomy

Background: Chromosomal abnormalities contribute substantially to reproductive problems, but the role of environmental risk factors has received little attention. Objectives: We evaluated the association of polychlorinated biphenyl (PCB) and dichlorodiphenyldichloroethylene (p,p´-DDE) exposures with sperm sex-chromosome disomy. Methods: We conducted a cross-sectional study of 192 men from subfertile couples. We used multiprobe fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 to determine XX, YY, XY, and total sex-chromosome disomy in sperm nuclei. Serum was analyzed for concentrations of 57 PCB congeners and p,p´-DDE. Poisson regression models were used to calculate incidence rate ratios (IRRs) for disomy by exposure quartiles, controlling for demographic characteristics and semen parameters. Results: The median percent disomy was 0.3 for XX and YY, 0.9 for XY, and 1.6 for total sex-chromosome disomy. We observed a significant trend of increasing IRRs for increasing quartiles of p,p´-DDE in XX, XY, and total sex-chromosome disomy, and a significant trend of increasing IRRs for increasing quartiles of PCBs for XY and total sex-chromosome disomy; however, there was a significant inverse association for XX disomy. Conclusions: Our findings suggest that exposure to p,p´-DDE may be associated with increased rates of XX, XY, and total sex-chromosome disomy, whereas exposure to PCBs may be associated with increased rates of YY, XY, and total sex-chromosome disomy. In addition, we observed an inverse association between increased exposure to PCBs and XX disomy. Further work is needed to confirm these findings

How Will the SCOTUS Affirmative Action Ruling Affect the Integrity of University Leaders?

On June 29, 2023, the Supreme Court of the United States (“SCOTUS”) ruled on addressing the legality of race-conscious affirmative action in college admissions programs in Students for Fair Admission, Inc. Based on the ruling, our study examined the literature to answer one research question: How will the SCOTUS affirmative action ruling affect the integrity of university leaders? We now understand how post-affirmative action could affect the integrity of university leaders. We now know more about (1) leaders’ perspectives post-SCOTUS ruling, (2) leaders’ influences on the educational culture, and (3) the effects that leaders’ integrity could have after the SCOTUS Title VI 2023 ruling. We make five conjectures about what we believe will guide university leaders’ integrity post-SCOTUS ruling

Two Small Planets Transiting HD 3167

We report the discovery of two super-Earth-sized planets transiting the bright (V = 8.94, K = 7.07) nearby late G-dwarf HD 3167, using data collected by the K2 mission. The inner planet, HD 3167 b, has a radius of 1.6 R_e and an ultra-short orbital period of only 0.96 days. The outer planet, HD 3167 c, has a radius of 2.9 R_e and orbits its host star every 29.85 days. At a distance of just 45.8 +/- 2.2 pc, HD 3167 is one of the closest and brightest stars hosting multiple transiting planets, making HD 3167 b and c well suited for follow-up observations. The star is chromospherically inactive with low rotational line-broadening, ideal for radial velocity observations to measure the planets' masses. The outer planet is large enough that it likely has a thick gaseous envelope which could be studied via transmission spectroscopy. Planets transiting bright, nearby stars like HD 3167 are valuable objects to study leading up to the launch of the James Webb Space Telescope.Comment: Accepted by ApJL. 6 pages, 1 figure, 2 table

Fractional Synthetic Rate and Markers of Protein Turnover are Altered in the Diaphragms of Cachectic Mice

Cancer cachexia, a wasting syndrome characterized by rapid skeletal muscle wasting and fat loss, directly accounts for up to 20-40% of cancer-related deaths. All muscles, including respiratory muscles, are susceptible to atrophy because cancer cachexia is a systemic disease. Atrophy of the primary breathing muscle, the diaphragm, can lead to respiratory distress, which is commonly associated with a cachectic phenotype. Indeed, the diaphragm is more susceptible to atrophy in certain conditions, but little is known about the effects of cancer-cachexia on protein turnover in the diaphragm. Therefore, investigations into the alterations in protein turnover could provide insight to the molecular events and provide valuable information in the search for therapeutic targets. PURPOSE: The purpose of this study was to describe changes in diaphragmatic protein synthesis and molecular markers of synthesis and degradation during the progression of cancer cachexia. METHODS: C57BL6/J mice (8 wks old) were implanted with 1X106 Lewis Lung Carcinoma cells (LLC) or Phosphate-Buffered Saline (PBS, control). Tumors developed over a 1-4 wk time course and diaphragms were harvested at each time point (1, 2, 3, or 4 wks). Fractional synthetic rates (FSR) were determined using deuterium incorporation into muscle. Selected markers of protein synthesis and degradation pathways were analyzed by immunoblot analysis. One-Way ANOVA was used for statistical analyses, with significance set at pRESULTS: FSR trended downward over time, but did not reach significance. Similar to FSR, anabolic signaling markers (4EBP-1, ERK1/2, Deptor) did not demonstrate significant differences. p62, an autophagic degradation marker, was significantly less than PBS in 3 wk diaphragms (

Disuse Atrophy Occurs Without a Change in Mitochondrial Respiratory Control Ratio During Hindlimb Unloading in Mice

Skeletal muscle atrophy commonly occurs during prolonged periods of inactivity, however, the precise mechanisms that cause muscle atrophy have yet to be determined. Specifically, a controversy exists on whether mitochondrial dysfunction is a cause or consequence of disuse muscle atrophy. PURPOSE: The purpose of this study was to determine if a change in the respiratory control ratio, which is a ratio of maximal O2 respiration to leak respiration, could be detected prior to muscle atrophy in a time-course study in mice. METHODS: Disuse atrophy was induced using hindlimb unloading (HU) in adult, C57BL/6J male mice for 0 (control), 1, 2, 3, or 7 days (n=~6-8/group). Following completion, gastrocnemius and soleus muscles were weighed and assessed for mitochondrial function in permeabilized muscle fibers. Here, we define mitochondrial function as the respiratory control ratio (RCR) determined by maximal ADP stimulated respiration (State 3) divided by leak or ATP synthase inhibited (state 4) respiration. A one-way ANOVA was used to determine differences between means. When significant F ratios were found, a Tukey post-hoc was used to compare differences between means. Values presented are mean ± standard error RESULTS: In both the gastrocnemius and soleus, muscle mass was not significantly different from control at day 1, but was significantly lower at 2, 3, and 7-day timepoints. In contrast, there was no significant difference in RCR in gastrocnemius (control 3.11±0.20, 1 day 2.96±0.60, 2 day 3.07±0.31, 3 day 3.08±0.25, 7 day 3.41± .29) or soleus (control 2.33±0.33, 1 day 2.77±0.33, 2 day 3.03±0.51, 3 day 2.93±0.30, 7 day 2.78±0.48). CONCLUSION: It is well established that HU causes rapid muscle atrophy. These data support mitochondrial RCR does decrease before muscle atrophy in either gastrocnemius or soleus muscle, and therefore may not be a primary cause of HU-induced muscle atrophy in mice

Tau-mediated axonal degeneration is prevented by activation of the WldS pathway

Tauopathy is characterized by neuronal dysfunction and degeneration occurring as a result of changes to the microtubule-associated protein tau. The neuronal changes evident in tauopathy bear striking morphological resemblance to those reported in models of Wallerian degeneration. The mechanisms underpinning Wallerian degeneration are not fully understood although it can be delayed by the expression of the slow Wallerian degeneration (WldS) protein, which has also been demonstrated to delay axonal degeneration in some models of neurodegenerative disease. Given the morphological similarities between tauopathy and Wallerian degeneration, this study investigated whether tau-mediated phenotypes can be modulated by co-expression of WldS. In a Drosophila model of tauopathy in which expression of human 0N3R tau protein leads to progressive age-dependent phenotypes, WldS was expressed with and without activation of the downstream pathway. The olfactory receptor neuron circuit OR47b was used for these studies in adults, and the larval motor neuron system was employed in larvae. Tau phenotypes studied included neurodegeneration, axonal transport, synaptic deficits and locomotor behaviour. Impact on total tau was ascertained by assessing total, phosphorylated and misfolded tau levels by immunohistochemistry. Activation of the pathway downstream of WldS completely suppressed tau-mediated degeneration. This protective effect was evident even if the pathway downstream of WldS was activated several weeks after tau-mediated degeneration had become established. Though total tau levels were not altered, the protected neurons displayed significantly reduced MC1 immunoreactivity suggestive of clearance of misfolded tau, as well as a trend for a decline in tau species phosphorylated at the AT8 and PHF1 epitopes. In contrast, WldS expression without activation of the downstream protective pathway did not rescue tau-mediated degeneration in adults or improve tau-mediated neuronal dysfunction including deficits in axonal transport, synaptic alterations and locomotor behaviour in tau-expressing larvae. This collectively implies that the pathway mediating the protective effect of WldS intersects with the mechanism(s) of degeneration initiated by tau and can effectively halt tau-mediated degeneration at both early and late stages. Understanding the mechanisms underpinning this protection could identify much-needed disease-modifying targets for tauopathies.</p

Environmental Exposure to Polychlorinated Biphenyls and p,p´-DDE and Sperm Sex-Chromosome Disomy

Background: Chromosomal abnormalities contribute substantially to reproductive problems, but the role of environmental risk factors has received little attention