Parathyroidectomy and the Development of New Depression Among Adults With Primary Hyperparathyroidism.

Importance: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with neuropsychiatric symptoms. Although parathyroidectomy has been associated with improvement of preexisting depression among adults with PHPT, the effect of parathyroidectomy on the development of new depression is unknown. Objective: To determine the effect of early parathyroidectomy on the incidence of new depression among adults with PHPT compared with nonoperative management. Design, Setting, and Participants: Analyzed data included observational national Veterans Affairs data from adults with a new diagnosis of PHPT from 2000 through 2019 using target trial emulation with cloning, a biostatistical method that uses observational data to emulate a randomized clinical trial. New depression rates were compared between those treated with early parathyroidectomy vs nonoperative management using an extended Cox model with time-varying inverse probability censoring weighting, adjusted for patient demographics, comorbidities, and depression risk factors. Eligible adults with a new biochemical diagnosis of PHPT, excluding those with past depression diagnoses, residing in an assisted living/nursing facility, or with Charlson Comorbidity Index score higher than 4 were included. These data were analyzed January 4, 2023, through June 15, 2023. Exposure: Early parathyroidectomy (within 1 year of PHPT diagnosis) vs nonoperative management. Main Outcome: New depression, including among subgroups according to patient age (65 years or older; younger than 65 years) and baseline serum calcium (11.3 mg/dL or higher; less than 11.3 mg/dL). Results: The study team identified 40 231 adults with PHPT and no history of depression of whom 35896 were male (89%) and the mean (SD) age was 67 (11.3) years. A total of 3294 patients underwent early parathyroidectomy (8.2%). The weighted cumulative incidence of depression was 11% at 5 years and 18% at 10 years among patients who underwent parathyroidectomy, compared with 9% and 18%, respectively, among nonoperative patients. Those treated with early parathyroidectomy experienced no difference in the adjusted rate of new depression compared with nonoperative management (hazard ratio, 1.05; 95% CI, 0.94-1.17). There was also no estimated effect of early parathyroidectomy on new depression in subgroup analyses based on patient age or serum calcium. Conclusions: In this study, there was no difference in the incidence of new depression among adults with PHPT treated with early parathyroidectomy vs nonoperative management, which is relevant to preoperative discussions about the benefits and risks of operative treatment.

Death rituals and quality of life of bereaved relatives during the COVID-19 pandemic: Results of the observational CO-LIVE study.

Grief is a normal reaction after the death of a loved one. Death rituals are an integral part of the mourning processes. Not being able to carry out death rituals can affect relatives' quality of life. The aim was to evaluate death rituals during COVID-19 and their association with relatives' quality of life. In a Swedish nation-wide study relatives to persons who died during the COVID-19-pandemic received questionnaires about their quality of life and how they could perform death rituals. Association between quality of life and death rituals was analyzed with linear regression. Of the 324 relatives, a minority indicated that their loved one's funeral (17%) met their wishes. Not being able to carry out the funeral as desired was significantly associated with a lower quality of life (p = 0.006). The experiences during the pandemic revealed that it is important for people to perform death rituals according to their wishes.

Dietary patterns during pregnancy and maternal and birth outcomes in women with type 1 diabetes: the Environmental Determinants of Islet Autoimmunity (ENDIA) study.

AIMS/HYPOTHESIS: Dietary patterns characterised by high intakes of vegetables may lower the risk of pre-eclampsia and premature birth in the general population. The effect of dietary patterns in women with type 1 diabetes, who have an increased risk of complications in pregnancy, is not known. The aim of this study was to investigate the relationship between dietary patterns and physical activity during pregnancy and maternal complications and birth outcomes in women with type 1 diabetes. We also compared dietary patterns in women with and without type 1 diabetes. METHODS: Diet was assessed in the third trimester using a validated food frequency questionnaire in participants followed prospectively in the multi-centre Environmental Determinants of Islet Autoimmunity (ENDIA) study. Dietary patterns were characterised by principal component analysis. The Pregnancy Physical Activity Questionnaire was completed in each trimester. Data for maternal and birth outcomes were collected prospectively. RESULTS: Questionnaires were completed by 973 participants during 1124 pregnancies. Women with type 1 diabetes (n=615 pregnancies with dietary data) were more likely to have a 'fresh food' dietary pattern than women without type 1 diabetes (OR 1.19, 95% CI 1.07, 1.31; p=0.001). In women with type 1 diabetes, an increase equivalent to a change from quartile 1 to 3 in 'fresh food' dietary pattern score was associated with a lower risk of pre-eclampsia (OR 0.37, 95% CI 0.17, 0.78; p=0.01) and premature birth (OR 0.35, 95% CI 0.20, 0.62, p<0.001). These associations were mediated in part by BMI and HbA1c. The 'processed food' dietary pattern was associated with an increased birthweight (ß coefficient 56.8 g, 95% CI 2.8, 110.8; p=0.04). Physical activity did not relate to outcomes. CONCLUSIONS/INTERPRETATION: A dietary pattern higher in fresh foods during pregnancy was associated with sizeable reductions in risk of pre-eclampsia and premature birth in women with type 1 diabetes.

Patient-derived colon epithelial organoids reveal lipid-related metabolic dysfunction in pediatric ulcerative colitis.

Ulcerative colitis (UC) is associated with epithelial metabolic derangements which exacerbate gut inflammation. Patient-derived organoids recapitulate complexities of the parent tissue in health and disease; however, whether colon organoids (colonoids) model the metabolic impairments in the pediatric UC epithelium is unclear. Here, we developed colonoid lines from pediatric patients with endoscopically active UC, inactive UC, and those without endoscopic or histologic evidence of colon inflammation (non-IBD controls) to interrogate functional metabolic differences in the colon epithelia. We demonstrate that colonoids from active UC patients exhibit hypermetabolic features and cellular stress, specifically during differentiation. Hypermetabolism in differentiating active UC colonoids was driven, in part, by increased proton leak, and supported by enhanced glycolytic capacity and dysregulated neutral lipid accumulation. Transcriptomic and pathway analyses indicated a role for PPAR-α in lipid-induced hypermetabolism in aUC colonoids, which was validated by PPAR-α activation in non-IBD colonoids. Accordingly, limiting neutral lipid accumulation in active UC colonoids through pharmacological inhibition of PPAR-α induced a metabolic shift towards glucose utilization, suppressed hypermetabolism and chemokine secretion, and improved markers of cellular stress and epithelial differentiation. Taken together, we reveal a role for lipid-related metabolic dysfunction in the pediatric UC epithelium and support the advancement of colonoids as a preclinical human model for testing epithelial-directed therapies against such metabolic dysfunction.

Trends in the use of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and recently diagnosed colorectal, lung, or prostate cancer.

INTRODUCTION: Biologic disease-modifying antirheumatic drugs (bDMARD) are often discontinued when a patient with rheumatoid arthritis (RA) is diagnosed with cancer. Our aim was to determine trends in bDMARD utilization in patients with RA and recently diagnosed cancer. METHOD: We examined two national claims databases to identify adults with RA and recently diagnosed colorectal, lung, or prostate cancer (Optum's de-identified Clinformatics® Data Mart Database 2008-2022, and Surveillance, Epidemiology, and End Results Program (SEER) Medicare-linked 2008-2017). We determined time trends in bDMARD and tumor necrosis factor inhibitor (TNFi) prescriptions during the first 3 years after cancer with Cochram-Armitage tests and multivariable logistic regression. Cancer cohorts were analyzed separately. RESULTS: We included 3595 patients in all six cohorts (in Clinformatics® 503 with colorectal, 468 with lung, and 440 with prostate cancer; in SEER-Medicare 580 with colorectal, 1010 with lung, and 594 with prostate cancer). No significant increase was observed in bDMARD or TNFi utilization over time. Overall, use of bDMARD within the first 3 years of follow-up ranged from 16.7% (Clinformatics® lung cohort) to 29.7% (SEER-Medicare colorectal cohort). The major predictor of bDMARD utilization was prior use in the 3 months before cancer diagnosis (p < 0.001 for all cancers) and earlier cancer stage (p < 0.001 in colorectal and lung cancer and p = 0.05 in prostate cancer). CONCLUSIONS: Use of bDMARD in patients with RA and recently diagnosed common cancers has not increased since 2008. Additional evidence on the safety of bDMARD in patients with early cancer is needed to ensure appropriate management of their RA. Key Points • Use of bDMARD and TNFi in patients with RA and early colorectal, lung, or prostate cancer has been stable since 2008, with no significant increases over time. • The major determinant of receiving bDMARD after cancer diagnosis was prior treatment with bDMARD in the prior 3 months before cancer. • Patients with advanced cancer stage and distant metastases were less likely to receive bDMARD and TNFi than those at early stages of disease.

High oleic soybean oil maintains milk fat and increases apparent total-tract fat digestibility and fat deposition in lactating dairy cows.

Due to the bioactive properties of oleic acid, the objective of this study was to feed high oleic soybean oil (HOSO) to lactating cows and evaluate milk production, body composition, and apparent total-tract digestibility variables. Thirty Holstein cows (n = 16 primiparous, n = 14 multiparous at 87 ± 26 DIM at the start of the trial) were used in a crossover design with periods lasting 21 d. The treatments were a control (CON) diet with no added soybean oil and a HOSO diet with 1.5% diet DM of high oleic soybean oil. Dry matter and milk production data were collected the last 7 d of each period, and milk composition was collected the last 3 d of each period. Fecal samples were collected 6 times during the last 3 d of each period. Body weights were collected on the last 3 d of each period after the morning milking and ultrasound scans of the longissimus dorsi on the last day of each period. Compared with CON, HOSO did not affect DMI, milk production, and milk component yields. However, a parity effect was observed with multiparous cows having increased DMI (5.9 kg/d), milk production (11.2 kg/d), and component yields, with no treatment by parity interactions. Milk fat concentration tended to be greater for HOSO cows. Body weight data tended to have an interaction between treatment and parity, with multiparous HOSO cows having increased BW compared with CON and no effect on primiparous cows. Similar treatment by parity effects were observed for BCS. Compared with CON, HOSO increased fat depth by 0.44 mm and apparent total-tract fat digestibility by 12 percentage units. The results of this study indicated no detrimental effects of HOSO on milk production parameters with an increase in milk fat concentration, fat digestibility, and deposition compared with a control diet.

Implementation of a Novel Seizure Assessment Tool for Unified Seizure Evaluation Improves Nurse Response.

ABSTRACT: BACKGROUND: Ictal and postictal testing is an essential aspect of clinical care when diagnosing and treating seizures. The epilepsy monitoring unit (EMU) has standard operating procedures for nursing care during and after seizure events, but there is limited interrater reliability. Streamlining ictal and postictal testing processes may enhance care consistency for patients in the EMU unit. The purpose of this study was to create an ictal and postictal seizure assessment tool that would increase the consistency of nursing assessment for EMU patients. METHODS: This prospective study had 4 phases: baseline assessment, instrument development, staff education, and field testing. During baseline assessment, an advanced practice provider and an epilepsy fellow graded nurse ictal and postictal assessment via survey questions. After instrument development, education, and implementation, the same survey was administered to determine if nursing consistency in assessing seizure events improved. The tool used in this study was created by a team of clinical experts to ensure consistency in the assessment of seizure patients. RESULTS: A total of 58 first seizure events were collected over a 6-month intervention period; 27 in the pretest and 31 in the posttest. Paired t test analyses revealed significant improvement in the clinical testing domains of verbal language function (P < .005), motor function (P < .0005), and item assessment order (P < .005) postintervention. There was nonsignificant improvement in the domains of responsiveness (feeling [P = .597], using a code word [P = .093]) and visual language function (P = .602). CONCLUSION: The data captured in this study support the need for this instrument. There is strong need to increase consistency in assessing seizure events and to promote continued collaboration among clinical teams to enhance care to EMU patients. Validation of this instrument will further improve team collaboration by allowing nurses to contribute to their fullest extent.

Epithelial Interleukin-1 Receptor-Like-1 Activation Is Contingent on Interleukin-33 Isoforms and Asthma-Related Receptor Variation.

INTRODUCTION: The interleukin-33/interleukin-1 receptor-like-1 (IL-33/IL1RL1) signalling pathway is implicated in asthma pathogenesis, with IL1RL1 nonsynonymous genetic polymorphisms associated with disease risk. We aimed to determine these variants' effect on IL1RL1 signalling induced by different IL33 isoforms thought to be elevated in the asthmatic airway. METHOD: In a project funded by GSK plc, which has developed an IL-33 receptor inhibitor for asthma treatment, human embryonic kidney 293 (HEK293) cells expressing secreted embryonic alkaline phosphatase (SEAP) driven by a nuclear factor kappa-beta (NF-κB) promoter, were transiently transfected with IL1RL1, containing one of four extracellular and Toll/interleukin 1 receptor (TIR) domain haplotypes. Cells were stimulated with seven different splice and proteolytic-generated IL-33 isoforms (0.001-50 ng/mL) for 24 h. Supernatant SEAP activity and interleukin-8 (IL-8) levels were determined. Primary human bronchial epithelial cells (HBECs) representing different genotype carriers were stimulated with IL-33112-270 (50 ng/mL) and induced IL-8 mRNA expression measured. RESULTS: HEK293 cells carrying both asthma extracellular and TIR domain IL1RL1 risk haplotypes presented maximal IL33-driven signalling, with minimal signalling after IL-33 activation in other protective haplotypes. All IL-33 isoforms activated IL1RL1 but with differing magnitudes. Proteolytically cleaved IL3395-270 and IL33106-270 had the greatest effect and the IL33113-270, and Exon 3,4 deletion isoform exhibited the lowest. The effect of extracellular and TIR domain genetic variants on receptor signalling was replicated in primary HBECs. Maximal IL1RL1 signalling was observed in cells carrying both extracellular and TIR signalling domain risk haplotypes. CONCLUSIONS: Overall, our study suggests asthma patients carrying the extracellular and TIR domain risk haplotype and have a lung microenvironment that promotes elevated levels of cleaved IL33, particularly where IL3395-270 and IL33106-270 may be more amenable to IL33/IL1RL1 targeting.

Akkermansia in the gastrointestinal tract as a modifier of human health.

Akkermansia sp are common members of the human gut microbiota. Multiple reports have emerged linking the abundance of A. muciniphila to health benefits and disease risk in humans and animals. This review highlights findings linking Akkermansia species in the gastrointestinal (GI) tract to health outcomes across a spectrum of disorders, encompassing those that affect the digestive, respiratory, urinary, and central nervous systems. The mechanism through which Akkermansia exerts a beneficial versus a detrimental effect on health is likely dependent on the genetic makeup of the host metabolic capacity and immunomodulatory properties of the strain, the competition or cooperation with other members of the host microbiota, as well as synergy with co-administered therapies.

Culture and other direct detection methods to diagnose human granulocytic anaplasmosis.

OBJECTIVES: We sought to assess the performance of 3 laboratory tests on blood specimens for direct detection of Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA), in patients tested at a single medical institution in New York State. METHODS: Direct tests included microscopic blood smear examination for intragranulocytic inclusions, polymerase chain reaction (PCR), and culture using the HL-60 cell line. The HGA cases testing positive by only 1 direct test were not included, unless HGA was confirmed by acute or convalescent serology using an indirect immunofluorescent assay. RESULTS: From 1997 to 2009, 71 patients with HGA were diagnosed by at least 1 of the 3 direct test methods. For the subgroup of 55 patients who were tested using all 3 methods, culture was positive for 90.9% (50/55) vs 81.8% (45/55) for PCR vs 63.6% (35/55) for blood smear (P =.002). Most cultures (79.3%) were detected as positive within 1 week of incubation. CONCLUSIONS: Although using culture to detect A phagocytophilum is likely not amenable for implementation in most hospital laboratories, in our experience, culture had the highest yield among the direct tests evaluated.

implementation of healthy heart ambassador to improve blood pressure control at community health centers in Texas.

BACKGROUND: Hypertension is one of the most prevalent chronic diseases in the United States and can increase a person's risk of stroke and other cardiovascular complications. Yet only 1 in 4 people with high blood pressure in the United States have their blood pressure managed. To improve hypertension control, we supported 9 health centers in Texas with the implementation of the Healthy Heart Ambassador Blood Pressure Self-Monitoring (HHA) Program. METHODS: We provided health center training using the HHA Program Facilitation Training Guide, recorded barriers to implementing the HHA program, and employed strategies to overcome those barriers. RESULTS: There were 68 staff members from the health centers trained to deliver the HHA program. Three health centers successfully implemented all three major components of HHA, three were able to implement two components, two adopted two components, and one withdrew due to insufficient capacity. Capability, technology infrastructure, and motivation were among the barriers most referenced. CONCLUSION: Clinic non-physician team members delivering the HHA program will need training and ongoing technical assistance to overcome implementation barriers.

In vivo antischistosomal efficacy of Porcelia ponderosa γ-lactones.

BACKGROUND: Schistosomiasis, caused by the parasitic blood fluke Schistosoma mansoni, is a significant global health concern, particularly in tropical and subtropical regions. The available chemotherapeutic drug is restricted to praziquantel with present problems related to efficacy, toxicity and resistance, justifying the search for new drugs. Different natural products, including γ-lactones, have demonstrated anthelmintic activity. Thus, in this study, new γ-lactones from Porcelia ponderosa were investigated for their anti-S. mansoni effects in vitro and in vivo. PURPOSE: To evaluate the therapeutical potential against S. mansoni of the mixture of γ-lactones 1 + 2 obtained from Porcelia ponderosa seeds. STUDY DESIGN AND METHODS: The precipitate formed during the concentration of CH2Cl2 extract from seeds of P. ponderosa showed to be composed by a mixture of the new γ-lactones 1 + 2 (in a ratio 77:23) which were chemically characterized using NMR and ESI-HRMS. This mixture was evaluated in vitro and in vivo against S. mansoni, using a murine model of schistosomiasis. Additionally, toxicity of the mixture of 1 + 2 (77:23) was determined using mammalian cell lines (in vitro) or the model organism Caenorhabditis elegans (in vivo). RESULTS: Seeds of P. ponderosa afforded a mixture of two unreported γ-lactones, 3­hydroxy-4-methylene-2-(tetracosa-17'Z,23'-diene-13',15'-diynyl)­but-2-enolide (1) and 3­hydroxy-4-methylene-2-(tetracos-17'Z-ene-13',15'-diynyl)­but-2-enolide (2). Initially, the antischistosomal activity of the mixture of 1 + 2 (77:23) was investigated in vitro, and obtained results demonstrate reduced activity against Schistosoma mansoni worms (EC50 of 83.3 µg/ml) in comparison to positive control praziquantel (EC50 of 1.5 µg/ml). However, when tested in vivo using oral administration at 400 mg kg-1, the standard dose used in the murine model of schistosomiasis, the mixture of 1 + 2 (77:23) revealed expressive reductions in both worm burden (65.7 %) and egg production (97.2 %), similar of those observed to praziquantel (89.7 % and 91.5 %, respectively). On the other hand, when treated using 200 and 100 mg kg-1, reductions in worm burden (25.7 and 12.4 %) and egg production (33.6 and 13.3 %) were also observed. Importantly, the mixture of 1 + 2 (77:23) exhibited no toxicity using mammalian cell lines (in vitro) or C. elegans (in vivo). CONCLUSION: Considering the promising in vivo activity of γ-lactones from P. ponderosa, the mixture of 1 + 2 (77:23) can be considered as promising candidate for the development of novel antischistosomal therapeutics, underscoring the importance of biodiversity exploration in the search for effective treatments against neglected tropical diseases.

Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors.

The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with central nervous system (CNS) cancer. We performed comprehensive profiling of CSF circulating tumor DNA (ctDNA) in 711 patients using an FDA-authorized platform (MSK-IMPACT™) in a hospital laboratory. We identified genetic alterations in 489/922 (53.0%) CSF samples with clinically documented CNS tumors. None of 85 CSF samples from patients without CNS tumors had detectable ctDNA. The distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Repeated CSF ctDNA examinations from the same patients identified clonal evolution and emergence of resistance mechanisms. ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors.

An exploration of available methods and tools to improve the efficiency of systematic review production: a scoping review.

BACKGROUND: Systematic reviews (SRs) are time-consuming and labor-intensive to perform. With the growing number of scientific publications, the SR development process becomes even more laborious. This is problematic because timely SR evidence is essential for decision-making in evidence-based healthcare and policymaking. Numerous methods and tools that accelerate SR development have recently emerged. To date, no scoping review has been conducted to provide a comprehensive summary of methods and ready-to-use tools to improve efficiency in SR production. OBJECTIVE: To present an overview of primary studies that evaluated the use of ready-to-use applications of tools or review methods to improve efficiency in the review process. METHODS: We conducted a scoping review. An information specialist performed a systematic literature search in four databases, supplemented with citation-based and grey literature searching. We included studies reporting the performance of methods and ready-to-use tools for improving efficiency when producing or updating a SR in the health field. We performed dual, independent title and abstract screening, full-text selection, and data extraction. The results were analyzed descriptively and presented narratively. RESULTS: We included 103 studies: 51 studies reported on methods, 54 studies on tools, and 2 studies reported on both methods and tools to make SR production more efficient. A total of 72 studies evaluated the validity (n = 69) or usability (n = 3) of one method (n = 33) or tool (n = 39), and 31 studies performed comparative analyses of different methods (n = 15) or tools (n = 16). 20 studies conducted prospective evaluations in real-time workflows. Most studies evaluated methods or tools that aimed at screening titles and abstracts (n = 42) and literature searching (n = 24), while for other steps of the SR process, only a few studies were found. Regarding the outcomes included, most studies reported on validity outcomes (n = 84), while outcomes such as impact on results (n = 23), time-saving (n = 24), usability (n = 13), and cost-saving (n = 3) were less often evaluated. CONCLUSION: For title and abstract screening and literature searching, various evaluated methods and tools are available that aim at improving the efficiency of SR production. However, only few studies have addressed the influence of these methods and tools in real-world workflows. Few studies exist that evaluate methods or tools supporting the remaining tasks. Additionally, while validity outcomes are frequently reported, there is a lack of evaluation regarding other outcomes.

A review of multiparametric ultrasound imaging in the clinical setting: scrotal contents.

The innovative techniques in ultrasound have added a new dimension to investigating superficially located areas such as the contents of the scrotal sac. High frequency transducers, improved technology with the addition of elastography, contrast enhanced ultrasound and microvascular imaging has resulted in a further improvement in diagnostic capabilities. The ability to clearly demonstrate the presence or absence of vascularity within the area under investigation adds an additional dimension to operator confidence in establishing the presence of infarction, global or segmental, or the walls and cavity of an abscess in the testis or epididymis. Increased vascularity of a tumor aids the differential diagnosis based on the flow dynamics of the microbubble contrast, benign lesions likely to retain contrast. Elastography has the ability to ascertain the stiffness of tissue, and when used in conjunction with other ultrasound methods adds to the understanding of the likelihood of a malignant abnormality being present. All the different techniques come under the umbrella term 'multiparametric ultrasound', with the application in the scrotal sac detailed in this article.

Applying trace element geochemistry of archaeological bone to study the coevolution of environmental change and human health in the Roman Empire.

Technological change has affected human health dating back to at least the Neolithic agricultural revolution. Growing evidence indicates widespread environmental pollution began with metallurgical practices and continues today. Environmental exposures to trace elements released from these practices have the potential to alter human body composition, such as bone mineral chemistry, especially for elements that are not homeostatically regulated. These signals can be used for inferences about human health, particularly when metallotoxins are detected in abundance. Therefore, trace element geochemistry of archaeological bone may provide a means to evaluate human health through time. However, diagenetic factors can hinder attempts to extract this information. Thus, we employed advanced analytical and interpretive methods to carefully distinct groups of European burials over about 1000 years to address questions of potentially toxic trace element exposures. Here, to address our hypothesis that Roman urbanization created one of the earliest urban toxic environment caused by multiple exposures, we present a comprehensive suite of bone trace element compositions of femora from burials spanning three distinct archaeological time periods (Bronze Age, Iron Age, and Roman period). All bone specimens were obtained from the anterior-mid shaft of carefully selected femora and processed using the same analytical techniques designed to mitigate soil contamination. Our data indicate that widespread environmental pollution accelerated in Londinium during the Roman Empire period, leading to conditions where population health would be vulnerable to environmental changes. Specifically, bone lead, silver, vanadium, arsenic, and cadmium concentrations were typically elevated and would likely be associated with multiple toxicities. In addition, bone iron levels were extremely high in some Londinium burials. Our interpretation is that the Romans inhabiting Londinium were not just poisoned by lead exposure as several previous studies show but by several metallotoxins.

Shigella and ETEC have replaced rotavirus as main causes of childhood diarrhea in Rwanda after ten years of rotavirus vaccination.

The causes of diarrhea after ten years of rotavirus vaccination in Rwanda were investigated in 496 children with and 298 without diarrhea using a real-time PCR. Rotavirus was detected in 11% of children with diarrhea (OR 2.48, P=0.002). Comparison of population attributable fractions (PAF) show that Shigella (PAF=11%) and ETEC-eltB (PAF=12%) have replaced rotavirus as the main causative agents. The PAF for rotavirus had declined from 41% pre-vaccination to 6.5%, indicating that rotavirus has become one among several similarly important causes of childhood diarrhea in Rwanda. A rotavirus genotype shift to G3P[8] points at the importance of continued genotype surveillance.

Microsporidia-cypovirus interactions during simultaneous infection of the tree defoliator Dendrolimus sibiricus (Lepidoptera: Lasiocampidae).

The Siberian moth, Dendrolimus sibiricus is a dangerous forest defoliator, the number one pest of boreal forests in Asia. Search for effective and ecologically friendly control measures drives attention to microbial pathogens. Viruses and microsporidia are obligate intracellular parasites widespread in insect populations causing either chronic or acute infections. Interactions of these pathogens vary from antagonistic to synergistic. The goal of the work was to test a recently discovered cytoplasmatic polyhedrosis virus (cypovirus) strain DsCPV-1 isolated from D.sibiricus, combined with a microsporidium, against D. sibiricus, by feeding the inoculum (viral polyhedral and microsporidian spores). Three different microsporidian parasites of lepidopterans were tested against D. sibiricus as monoinfection: Nosema bombycis from silkworm, N. pyrausta from corn borer, and Tubulinosema loxostegi from beet webworm. Nosema bombycis was the most virulent, with a median lethal time of 7 days in the first and second instars treated with 100,000 and 1 million spores/larva, respectively. Nosema bombycis (dose 100,000 spores/larva) was chosen to test it as mixed infection in combination with an extremely low dose of DsCPV-1 (1 polyhedron/larva) against two races of D. sibiricus second instar larvae (the fir-feeding race and the larch-feeding race). The mixed infection demonstrated the most prominent negative effect on larval lethal time and weight for the both tested races. Mixed infections showed a synergistic effect for the fir-feeding larvae but additive effect only for the larch feeding larvae. Both pathogens co-developed successfully in the larvae with equal ratio of producing inoculum. The combination of these entomopathogens is therefore promising for forest protection against the Siberian moth and could be the way to significantly decrease the amount of pathogens applied in field.

Subcutaneous adipose tissue radiodensity: An emerging risk factor for severe COVID-19.

BACKGROUND: Adipose tissue radiodensity and metabolic activity may influence COVID-19 outcomes. This study evaluated the association between adipose tissue characteristics and clinical outcomes in COVID-19 patients. METHODS: Two retrospective cohorts of hospitalized COVID-19 patients were analyzed. Subcutaneous adipose tissue radiodensity (SATR) and visceral adipose tissue radiodensity were assessed by computed tomography. Fluorine-18-labelled fluorodeoxyglucose PET/computed tomography measured adipose tissue metabolic activity. Associations with mortality, length of stay, ventilation requirement, and complications were examined using regression analyses. RESULTS: High SATR was independently associated with increased mortality risk (OR: 2.70; P = 0.033), longer hospitalization (P < 0.001), higher rates of mechanical ventilation (P = 0.007), and complications: acute kidney injury (P = 0.001), secondary infection (P = 0.007), shock (P = 0.010), and pulmonary embolism (P = 0.011). SATR positively correlated with SAT glucose uptake (ρ = 0.52) and negatively with leptin levels (ρ = -0.48). CONCLUSIONS: Elevated SATR at COVID-19 diagnosis predicts disease severity and worse outcomes. SATR is a potential prognostic biomarker for acute and chronic inflammatory conditions.