Evolution of immune genes is associated with the Black Death.

Infectious diseases are among the strongest selective pressures driving human evolution1,2. This includes the single greatest mortality event in recorded history, the first outbreak of the second pandemic of plague, commonly called the Black Death, which was caused by the bacterium Yersinia pestis3. This pandemic devastated Afro-Eurasia, killing up to 30-50% of the population4. To identify loci that may have been under selection during the Black Death, we characterized genetic variation around immune-related genes from 206 ancient DNA extracts, stemming from two different European populations before, during and after the Black Death. Immune loci are strongly enriched for highly differentiated sites relative to a set of non-immune loci, suggesting positive selection. We identify 245 variants that are highly differentiated within the London dataset, four of which were replicated in an independent cohort from Denmark, and represent the strongest candidates for positive selection. The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages. Finally, we show that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases, providing empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease.

OPA1 mutation affects autophagy and triggers senescence in autosomal dominant optic atrophy plus fibroblasts.

In several cases of mitochondrial diseases, the underlying genetic and bioenergetic causes of reduced oxidative phosphorylation (OxPhos) in mitochondrial dysfunction are well understood. However, there is still limited knowledge about the specific cellular outcomes and factors involved for each gene and mutation, which contributes to the lack of effective treatments for these disorders. This study focused on fibroblasts from a patient with Autosomal Dominant Optic Atrophy (ADOA) plus syndrome harboring a mutation in the Optic Atrophy 1 (OPA1) gene. By combining functional and transcriptomic approaches, we investigated the mitochondrial function and identified cellular phenotypes associated with the disease. Our findings revealed that fibroblasts with the OPA1 mutation exhibited a disrupted mitochondrial network and function, leading to altered mitochondrial dynamics and reduced autophagic response. Additionally, we observed a premature senescence phenotype in these cells, suggesting a previously unexplored role of the OPA1 gene in inducing senescence in ADOA plus patients. This study provides novel insights into the mechanisms underlying mitochondrial dysfunction in ADOA plus and highlights the potential importance of senescence in disease progression.

Frailty and survival in the 1918 influenza pandemic.

One of the most well-known yet least understood aspects of the 1918 influenza pandemic is the disproportionately high mortality among young adults. Contemporary accounts further describe the victims as healthy young adults, which is contrary to the understanding of selective mortality, which posits that individuals with the highest frailty within a group are at the greatest risk of death. We use a bioarchaeological approach, combining individual-level information on health and stress gleaned from the skeletal remains of individuals who died in 1918 to determine whether healthy individuals were dying during the 1918 pandemic or whether underlying frailty contributed to an increased risk of mortality. Skeletal data on tibial periosteal new bone formation were obtained from 369 individuals from the Hamann-Todd documented osteological collection in Cleveland, Ohio. Skeletal data were analyzed alongside known age at death using Kaplan-Meier survival and Cox proportional hazards analysis. The results suggest that frail or unhealthy individuals were more likely to die during the pandemic than those who were not frail. During the flu, the estimated hazards for individuals with periosteal lesions that were active at the time of death were over two times higher compared to the control group. The results contradict prior assumptions about selective mortality during the 1918 influenza pandemic. Even among young adults, not everyone was equally likely to die-those with evidence of systemic stress suffered greater mortality. These findings provide time depth to our understanding of how variation in life experiences can impact morbidity and mortality even during a pandemic caused by a novel pathogen.

Ancient pathogens provide a window into health and well-being.

This perspective draws on the record of ancient pathogen genomes and microbiomes illuminating patterns of infectious disease over the course of the Holocene in order to address the following question. How did major changes in living circumstances involving the transition to and intensification of farming alter pathogens and their distributions? Answers to this question via ancient DNA research provide a rapidly expanding picture of pathogen evolution and in concert with archaeological and historical data, give a temporal and behavioral context for heath in the past that is relevant for challenges facing the world today, including the rise of novel pathogens.

Climate change, human health, and resilience in the Holocene.

Climate change is an indisputable threat to human health, especially for societies already confronted with rising social inequality, political and economic uncertainty, and a cascade of concurrent environmental challenges. Archaeological data about past climate and environment provide an important source of evidence about the potential challenges humans face and the long-term outcomes of alternative short-term adaptive strategies. Evidence from well-dated archaeological human skeletons and mummified remains speaks directly to patterns of human health over time through changing circumstances. Here, we describe variation in human epidemiological patterns in the context of past rapid climate change (RCC) events and other periods of past environmental change. Case studies confirm that human communities responded to environmental changes in diverse ways depending on historical, sociocultural, and biological contingencies. Certain factors, such as social inequality and disproportionate access to resources in large, complex societies may influence the probability of major sociopolitical disruptions and reorganizations-commonly known as "collapse." This survey of Holocene human-environmental relations demonstrates how flexibility, variation, and maintenance of Indigenous knowledge can be mitigating factors in the face of environmental challenges. Although contemporary climate change is more rapid and of greater magnitude than the RCC events and other environmental changes we discuss here, these lessons from the past provide clarity about potential priorities for equitable, sustainable development and the constraints of modernity we must address.

Mitofusin 2 mutation drives cell proliferation in Charcot-Marie-Tooth 2A fibroblasts.

Dominant mutations in ubiquitously expressed mitofusin 2 gene (MFN2) cause Charcot-Marie-Tooth type 2A (CMT2A; OMIM 609260), an inherited sensory-motor neuropathy that affects peripheral nerve axons. Mitofusin 2 protein has been found to take part in mitochondrial fusion, mitochondria-endoplasmic reticulum tethering, mitochondrial trafficking along axons, mitochondrial quality control and various types of cancer, in which MFN2 has been indicated as a tumor suppressor gene. Discordant data on the mitochondrial altered phenotypes in patient-derived fibroblasts harboring MFN2 mutations and in animal models have been reported. We addressed some of these issues by focusing on mitochondria behavior during autophagy and mitophagy in fibroblasts derived from a CMT2AMFN2 patient with an MFN2650G > T/C217F mutation in the GTPase domain. This study investigated mitochondrial dynamics, respiratory capacity and autophagy/mitophagy, to tackle the multifaceted MFN2 contribution to CMT2A pathogenesis. We found that MFN2 mutated fibroblasts showed impairment of mitochondrial morphology, bioenergetics capacity, and impairment of the early stages of autophagy, but not mitophagy. Unexpectedly, transcriptomic analysis of mutated fibroblasts highlighted marked differentially expressed pathways related to cell population proliferation and extracellular matrix organization. We consistently found the activation of mTORC2/AKT signaling and accelerated proliferation in the CMT2AMFN2 fibroblasts. In conclusion, our evidence indicates that MFN2 mutation can positively drive cell proliferation in CMT2AMFN2 fibroblasts.

Medieval monastic health: Variation in skeletal signs of inflammation and developmental stress between religious orders in London.

OBJECTIVES: Previous bioarchaeological analyses of medieval monastic and nonmonastic cemeteries in London revealed evidence of lower risks of mortality, and thus better health, in the monastic settings. However, comparison of the two monastic communities, Bermondsey Abbey and Merton Priory, which adhered to different religious ideals, suggested lower risks of mortality in the former. This study examines patterns of skeletal biomarkers, which reflect developmental stress or inflammation, in an attempt to clarify the possible underlying mechanisms producing apparent health differences in these monastic communities. MATERIALS AND METHODS: This study uses skeletal data on age-at-death, periosteal new bone formation (PNBF), and cribra orbitalia from 558 adults (18 years of age and older) estimated to be male from Bermondsey Abbey and Merton Priory. Biomarker age patterns are assessed via Kaplan-Meier survival analysis and binary logistic regression. Differences in frequencies of biomarkers between the monastic sites are evaluated using Chi-square and hierarchical log-linear analyses. RESULTS: In general, PNBF is positively associated with age, and cribra orbitalia is negatively associated with age. The frequency of PNBF formation is significantly higher and that of cribra orbitalia is significantly lower in Bermondsey Abbey compared with Merton Priory. CONCLUSIONS: The differences in frequencies of these skeletal biomarkers support previous findings suggesting that health conditions were better in Bermondsey Abbey than in Merton Priory. The age patterns of cribra orbitalia suggest that these differences reflect conditions and the greater health-promoting effects of religiosity or isolation from the lay community in Bermondsey Abbey rather than differences in selective admissions processes.

Lumbopelvic fixation in the treatment of spinopelvic dissociation: union, complications, and neurologic outcomes of a multicenter case series.

PURPOSE: To review outcomes of spinopelvic dissociation treated with open lumbopelvic fixation. METHODS: We reviewed all cases of spinopelvic dissociation treated at three Level-I trauma centers with open lumbopelvic fixation, including those with adjunctive percutaneous fixation. We collected demographic data, associated injuries, pre- and postoperative neurologic status, pre- and postoperative kyphosis, and Roy-Camille classification. Outcomes included presence of union, reoperation rates, and complications involving hardware or wound. RESULTS: From an initial cohort of 260 patients with spinopelvic dissociation, forty patients fulfilled inclusion criteria with a median follow-up of 351 days. Ten patients (25%) had a combination of percutaneous iliosacral and open lumbopelvic repair. Average pre- and postoperative kyphosis was 30 degrees and 26 degrees, respectively. Twenty patients (50%) had neurologic deficit preoperatively, and eight (20%) were unknown or unable to be assessed. All patients presenting with bowel or bladder dysfunction (n = 12) underwent laminectomy at time of surgery, with 3 patients (25%) having continued dysfunction at final follow-up. Surgical site infection occurred in four cases (10%) and wound complications in two (5%). All cases (100%) went on to union and five patients (13%) required hardware removal. CONCLUSION: Open lumbopelvic fixation resulted in a high union rate in the treatment of spinopelvic dissociation. Approximately 1 in 6 patients had a wound complication, the majority of which were surgical site infections. Bowel and bladder dysfunction at presentation were common with the majority of cases resolving by final follow-up when spinopelvic dissociation had been treated with decompression and stable fixation.

Replication Protein A Enhances Kinetics of Uracil DNA Glycosylase on ssDNA and Across DNA Junctions: Explored with a DNA Repair Complex Produced with SpyCatcher/SpyTag Ligation.

DNA repair proteins participate in extensive protein-protein interactions that promote the formation of DNA repair complexes. To understand how complex formation affects protein function during base excision repair, we used SpyCatcher/SpyTag ligation to produce a covalent complex between human uracil DNA glycosylase (UNG2) and replication protein A (RPA). Our covalent "RPA-Spy-UNG2" complex could identify and excise uracil bases in duplex areas next to ssDNA-dsDNA junctions slightly faster than the wild-type proteins, but this was highly dependent on DNA structure, as the turnover of the RPA-Spy-UNG2 complex slowed at DNA junctions where RPA tightly engaged long ssDNA sections. Conversely, the enzymes preferred uracil sites in ssDNA where RPA strongly enhanced uracil excision by UNG2 regardless of ssDNA length. Finally, RPA was found to promote UNG2 excision of two uracil sites positioned across a ssDNA-dsDNA junction, and dissociation of UNG2 from RPA enhanced this process. Our approach of ligating together RPA and UNG2 to reveal how complex formation affects enzyme function could be applied to examine other assemblies of DNA repair proteins.

Association of Incomplete Neurovascular Imaging After Emergency Department Encounters for Transient Ischemic Attack and Odds of Subsequent Stroke: A National Medicare Analysis.

BACKGROUND. Multisociety guidelines recommend urgent brain and neurovascular imaging for patients with transient ischemic attack (TIA), to identify and treat modifiable stroke risk factors. Prior research suggests that most patients with TIA who present to the emergency department (ED) do not receive prompt neurovascular imaging. OBJECTIVE. The purpose of this study was to evaluate the association between incomplete neurovascular imaging workup during ED encounters for TIA and the odds of subsequent stroke. METHODS. This retrospective study obtained data from the Medicare Standard Analytical Files for calendar years 2016 and 2017; these files contain 100% samples of claims for Medicare beneficiaries. Information was extracted using ICD 10th revision (ICD-10) and CPT codes. Those patients who were discharged from an ED encounter with a TIA diagnosis and who underwent brain CT or brain MRI during or within 2 days of the encounter were identified. Patients were considered to have complete neurovascular imaging if they underwent cross-sectional vascular imaging of both the brain (brain CTA or brain MRA) and neck (neck CTA, neck MRA, or carotid ultrasound) during or within 2 days of the encounter. The association between incomplete neurovascular imaging and a new stroke diagnosis within the subsequent 90 days was tested by multivariable logistic regression analysis. RESULTS. The sample included 111,417 patients (47,370 men, 64,047 women; 26.0% older than 84 years) who had TIA ED encounters. A total of 37.3% of patients (41,592) had an incomplete neurovascular imaging workup. A new stroke diagnosis within 90 days of the TIA ED encounter occurred in 4.4% (3040/69,825) of patients with complete neurovascular imaging versus 7.0% (2898/41,592) of patients with incomplete neurovascular imaging. Incomplete neurovascular imaging was associated with increased likelihood of stroke within 90 days (OR, 1.30 [95% CI, 1.23-1.38]) after adjustment for patient characteristics (age, sex, race and ethnicity, high-risk comorbidities, median county household income) and hospital characteristics (region, rurality, number of beds, major teaching hospital designation). CONCLUSION. TIA ED encounters with incomplete neurovascular imaging were associated with higher odds of subsequent stroke occurring within 90 days. CLINICAL IMPACT. Increased access to urgent neurovascular imaging for patients with TIA may represent a target that could facilitate detection and treatment of modifiable stroke risk factors.

Sex differences in acute ischemic stroke presentation are a matter of infarct location.

INTRODUCTION: Recognition of stroke by Emergency Medical Services (EMS) is critical to initiate rapid emergency department treatment. Most prehospital stroke screening tools rely heavily on presentation with the classic symptoms of facial droop, speech changes, unilateral weakness. However, women may be less likely to present with classic symptoms and may also have different distributions of stroke by anatomical location. This study seeks to determine the association between biological sex, presentation with classic symptoms, and the location of the infarcted tissue. METHODS: This is a retrospective cohort study. Data from electronic health records were extracted for patients with acute ischemic stroke who presented via EMS to a single Comprehensive Stroke Center between January 1, 2018 and December 31, 2020. We used descriptive statistics characterize the cohort. Multivariable logistic regression identified factors associated with classic symptom presentation (facial droop, speech changes, and/or unilateral weakness). Biological sex, location of the infarct, stroke etiology, age and the interaction between sex and infarct location were assessed as covariates. RESULTS: There were 364 (58.6%) males and 257 (41.1%) females with an acute ischemic stroke included in this study. EMS documented one or more classic symptoms in 125 (72.3%) males and 161 (67.9%) females. There were no baseline differences in infarct location or presentation with classic symptoms as documented by EMS comparing males and females. Multivariate logistic regression found no association between biological sex and presentation with classic symptoms (Odds Ratio 1.08; 95% CI 0.58 to 1.55) after controlling for age, stroke location, etiology of stroke or the interaction between sex and infarct location. Presence of an anterior circulation infarct compared to posterior circulation infarct was positively associated with a classic presentation to EMS (Odds Ratio 3.41; 95% CI 2.15 to 5.41). CONCLUSIONS: This study found no difference in the frequency of patient presentation with classic stroke symptoms based on biological sex alone, nor a significant different in distribution of infarcts between males and females. Infarct location (i.e., involving the anterior circulation) was associated with a classic presentation. This suggests that the likelihood of presenting with classic stroke symptoms is not influenced by sex, but rather the location of the infarct.

Impact of Engaging Students in Health Survey Data Analysis and as Full Partners in School Change: Results From a Mixed Methods Study.

Young people demand and deserve participation in shaping the health and well-being of their community. Getting to Y: Youth Bring Meaning to the Youth Risk Behavior Survey (GTY) is a positive youth development initiative, whereby students analyze local youth health data and create change. This article adds definitive evidence to support the theoretical foundations of GTY expounded by Garnett et al. (2019). A mixed methods convergent study design, collecting quantitative data from pre- and postintervention surveys and qualitative data from focus groups, was enacted during the 2018-2019 school year. Survey participants were 256 students attending 20 Vermont middle/high schools. Surveys measured self-efficacy, health literacy, civic engagement, resiliency, and knowledge. Focus groups with 50 students solicited open-ended feedback. Wilcoxon signed-rank tests determined student-level change over time. Focus group transcripts were coded using grounded theory and a priori codes from the survey. Statistically significant improvements were seen in average scores from pre- to postintervention surveys in all five domains and differences in effect by gender. Results from the focus group complement the quantitative findings. Participation in GTY positively affected youth participant's understanding of their own health and well-being and increased agency to take action on behalf of themselves and their community. As the Youth Risk Behavior Survey is available nationwide, GTY is poised for replication to critically engage youth with relevant data to inform social change.

Systematic Review of Sex Differences in Ischemic Strokes Among Young Adults: Are Young Women Disproportionately at Risk?

BACKGROUND AND PURPOSE: Recent evidence suggests that young women (18-45 years) may be at higher risk of ischemic strokes than men of the same age. The goal of this systematic review is to reconcile and synthesize existing evidence of sex differences among young adults with ischemic strokes. METHODS: We searched PubMed from January 2008 to July 2021 for relevant articles and reviews and consulted their references. We included original studies that (1) were population based and (2) reported stroke incidence by sex or sex-specific incidence rate ratios of young adults ≤45 years. We excluded studies that (1) omitted measurements of error for incidence rates or incidence rate ratios, (2) omitted age adjustment, and (3) were not in English. Statistical synthesis was performed to estimate sex difference by age group (≤35, 35-45, and ≤45) and stroke type. RESULTS: We found 19 studies that reported on sex-specific stroke incidence among young adults, including 3 that reported on overlapping data. Nine studies did not find a statistically significant sex difference among young adults ≤45 years. Three studies found higher rates of ischemic stroke among men among young adults ≥30 to 35 years. Four studies found more women with ischemic strokes among young adults ≤35 years. Overall, in young adults ≤35 years, the estimated effect size favored more ischemic strokes in women (incidence rate ratio, 1.44 [1.18-1.76], I2=82%) and a nonsignificant sex difference in young adults 35 to 45 years (incidence rate ratio, 1.08 [0.85-1.38], I2=95%). CONCLUSIONS: Overall, there were 44% more women ≤35 years with ischemic strokes than men. This gap narrows in young adults, 35 to 45 years, and there is conflicting evidence whether more men or women have ischemic strokes in the 35 to 45 age group.

Sexual stature difference fluctuations in pre- and post-Black Death London as an indicator of living standards.

OBJECTIVES: The degree of sexual stature difference (SSD), the ratio of male to female height, is argued to be an indicator of living standards based on evidence that physical growth for males is more sensitive to environmental fluctuations. In a resource-poor environment, the degree of SSD is expected to be relatively low. The aim of this study is to comparatively assess SSD in medieval London in the context of repeated famine events and other environmental stressors before the Black Death (BD) and the improved living conditions that characterized the post-Black Death period. METHODS: To test the hypothesis that a poor nutritional environment resulted in decreased SSD in medieval London, this study compares adult individuals from early pre-Black Death (c. 1000-1200), late pre-Black Death (c. 1200-1250) and post-Black Death (c. 1350-1540) cemetery contexts from London. Maximum tibial,femoral, and lower limb lengths were used as a proxy for stature, and SSD was calculated using the Chakraborty and Majumber index. RESULTS: Compared to the late pre-BD period, we find a slighter higher degree of SSD in the post-BD period for all three stature proxies used. This increase is attributed to more exaggerated increases in stature for estimated males post-BD. CONCLUSIONS: This study demonstrates the importance of examining variables that are considered indicators of living standards in light of factors like selective mortality, catch-up growth, and urban migration patterns. Future research needs to further investigate how cultural and biological processes influence the mechanisms that produce adult stature.

Analysis of Stroke Care Among 2019-2020 National Emergency Medical Services Information System Encounters.

OBJECTIVES: Emergency Medicine Service (EMS) providers play a pivotal role in early identification and initiation of treatment for stroke. The objective of this study is to characterize nationwide EMS practices for suspected stroke and assess for gender-based differences in compliance with American Stroke Association (ASA) guidelines. MATERIALS AND METHODS: Using the 2019-2020 National Emergency Medical Services Information System (NEMSIS) Datasets, we identified encounters with an EMS designated primary impression of stroke. We characterized patient characteristics and EMS practices and assessed compliance with eight metrics for "guideline-concordant" care. Multivariable logistic regression modeled the association between gender and the primary outcome (guideline-concordant care), adjusted for age, EMS level of service, EMS geographical region, region type (i.e. urban or rural), and year. RESULTS: Of 693,177 encounters with a primary impression of stroke, overall compliance with each performance metric ranged from 18% (providing supplemental oxygen when the pulse oximetry is less than 94%) to 76% (less than 90sec from incoming call to EMS dispatch). 2,382 (0.39%) encounters were fully guideline-concordant. Women were significantly less likely than men to receive guideline-concordant care (adjusted OR 0.82, 95% CI 0.75-0.89; 0.36% women, 0.43% men with guideline-concordant care). CONCLUSIONS: A minority of patients received prehospital stroke care that was documented to be compliant with ASA guidelines. Women were less likely to receive fully guideline-compliant care compared to men, after controlling for confounders, although the difference was small and of uncertain climical importance. Further studies are needed to evaluate the underlying reasons for this disparity, its impact on patient outcomes, and to identify potential targeted interventions to improve prehospital stroke care.

Genes affecting ionizing radiation survival identified through combined exome sequencing and functional screening.

The study of genetic syndromes characterized by sensitivity to DNA damaging agents has provided important insights into the mechanisms that maintain genome stability and identified novel targets for cancer therapies. Here, we used exome sequencing to study 51 unrelated individuals with previously reported hypersensitivity to ionizing radiation as well as a range of neurologic, immunologic, and developmental features, but who did not clearly fit any previously defined genetic syndrome. Based on the combination of variant identification, computational evidence of deleteriousness, and functional screening, we identified three groups of subjects. Two subjects carried the bi-allelic loss of function variants in causative genes for known DNA damage response syndromes. Eight subjects carried the single loss of function variants in causative genes for DNA damage response syndromes, six of whom also carried predicted deleterious variants in other genes with DNA damage-related functions. Three subjects carried deleterious mutations in genes without obvious roles in DNA damage responses. However, treatment of U2OS cells with small interfering RNA targeting these genes resulted in significantly increased radiation sensitivity. Our results suggest that gene-gene interaction may contribute to ionizing radiation sensitivity as well as highlighting possible roles for several genes not obviously involved in the response to DNA damage.

Toward a bioarchaeology of urbanization: Demography, health, and behavior in cities in the past.

Urbanization is one of the most important settlement shifts in human history and has been the focus of research within bioarchaeology for decades. However, there have been limited attempts to synthesize the results of these studies in order to gain a broader perspective on whether or how urbanization affects the biology, demography, and behavior of humans, and how these potential effects are embodied in the human skeleton. This paper outlines how bioarchaeology is well-suited to examine urbanization in the past, and we provide an overview and examples of three main ways in which urbanization is studied in bioarchaeological research: comparison of (often contemporaneous) urban and rural sites, synchronic studies of the variation that exists within and between urban sites, and investigations of changes that occur within urban sites over time. Studies of urbanization, both within bioarchaeology and in other fields of study, face a number of limitations, including a lack of a consensus regarding what urban and urbanization mean, the assumed dichotomous nature of urban versus rural settlements, the supposition that urbanization is universally bad for people, and the assumption (at least in practice) of homogeneity within urban and rural populations. Bioarchaeologists can address these limitations by utilizing a wide array of data and methods, and the studies described here collectively demonstrate the complex, nuanced, and highly variable effects of urbanization.

Medieval menarche: Changes in pubertal timing before and after the Black Death.

OBJECTIVES: Bioarcheological evidence suggests stature increased in males but decreased in females after the Black Death (1348-1350 CE). Because tradeoffs between growth and reproduction can result in earlier ages at menarche and lower limb length, we assess menarcheal age between 1120 and 1540 CE to better understand the health of medieval adolescent females before and after the plague. MATERIALS AND METHODS: Our sample comprises 74 adolescent females from St. Mary Spital, London (1120-1540 CE) within the age range during which menarche occurs (10-25 years). They were assessed as being pre- or post-menarcheal and divided into three groups: Early Pre-Black Death (n = 13), Late Pre-Black Death (n = 38), and Post-Black Death (n = 23). Changes in the ages of pre- and post-menarcheal females were assessed using Mann-Whitney tests. RESULTS: The average age of post-menarcheal females increased from the Early- to Late Pre-Black Death periods and declined after the Black Death. CONCLUSIONS: Short stature can reflect unfavorable growth environments, while younger menarcheal age indicates improved living conditions. The paradoxical pattern of female, but not male, stature reduction after the Black Death might reflect the association of early menarche with lower limb length and signal that adolescent females experienced improved health conditions after the epidemic. Our focus on pre- and post-menarche within a limited age span provides a novel approach for inferring average ages of menarche over time. Pathways to skeletal development and reproductive investment are part of an integrated system, providing a bridge between life history research in bioarchaeology and human biology.

Association Between Chronic Inflammatory Diseases and Stroke-Associated Pneumonia - An Epidemiological Study.

BACKGROUND: Pneumonia, the most common post-acute ischemic stroke (AIS) infection, accounts for up to 30% of deaths after a stroke. Multiple chronic inflammatory diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease, are associated with increased risk of stroke and stroke morbidity. This study assessed the relationship between chronic inflammatory diseases and stroke-associated pneumonia (SAP). METHODS: Using data from the 2015-2017 National Inpatient Sample, we classified hospital discharges with a diagnosis of AIS as having ulcerative colitis, Crohn's disease, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, other chronic inflammatory diseases, multiple chronic inflammatory diseases, or none. With multivariable logistic regression, we assessed for associations between chronic inflammatory disease and in-hospital SAP or death. RESULTS: Among AIS discharges, there was a decreased risk of SAP among those with psoriasis or other chronic inflammatory diseases (adjusted odds ratio (aOR) 0.70, 95%CI 0.63-0.99; aOR 0.64, 95%CI, 0.46-0.89, respectively), compared to those without psoriasis and without other chronic inflammatory disease, respectively. Rheumatoid arthritis, psoriasis, and other chronic inflammatory diseases were associated with reduced in-hospital mortality (aOR 0.89, 95%CI 0.78-1.00; aOR 0.77, 95%CI 0.59-1.00; aOR 0.69, 95%CI 0.50-0.94, respectively). CONCLUSIONS: The risk of SAP and in-hospital mortality varies by chronic inflammatory disease - psoriasis and other chronic inflammatory diseases are associate with reduced rates of SAP, whereas rheumatoid arthritis, psoriasis and other chronic inflammatory disease were associated with reduced in-hospital mortality. Further investigations are needed to determine a relationship between the potential role of immunomodulation and the reduction in SAP and mortality in chronic inflammatory diseases.

Large Vessel Occlusion Prediction in the Emergency Department with National Institutes of Health Stroke Scale Components: A Machine Learning Approach.

OBJECTIVE: To determine the feasibility of using a machine learning algorithm to screen for large vessel occlusions (LVO) in the Emergency Department (ED). MATERIALS AND METHODS: A retrospective cohort of consecutive ED stroke alerts at a large comprehensive stroke center was analyzed. The primary outcome was diagnosis of LVO at discharge. Components of the National Institutes of Health Stroke Scale (NIHSS) were used in various clinical methods and machine learning algorithms to predict LVO, and the results were compared with the baseline method (aggregate NIHSS score with threshold of 6). The Area-Under-Curve (AUC) was used to measure the overall performance of the models. Bootstrapping (n = 1000) was applied for the statistical analysis. RESULTS: Of 1133 total patients, 67 were diagnosed with LVO. A Gaussian Process (GP) algorithm significantly outperformed other methods including the baseline methods. AUC score for the GP algorithm was 0.874 ± 0.025, compared with the simple aggregate NIHSS score, which had an AUC score of 0.819 ± 0.024. A dual-stage GP algorithm is proposed, which offers flexible threshold settings for different patient populations, and achieved an overall sensitivity of 0.903 and specificity of 0.626, in which sensitivity of 0.99 was achieved for high-risk patients (defined as initial NIHSS score > 6). CONCLUSION: Machine learning using a Gaussian Process algorithm outperformed a clinical cutoff using the aggregate NIHSS score for LVO diagnosis. Future studies would be beneficial in exploring prospective interventions developed using machine learning in screening for LVOs in the emergent setting.