Putative Causes Research Articles

Observational case-control study of small-fiber neuropathies, with regards on smoking and vitamin D deficiency and other possible causes.

Small fiber neuropathies (SFNs) are disorders of skin nerve endings inducing pruritus, burning pain, numbness, and paresthesia. The aims of this study were to search for putative etiologies of SFN and their occurrence in a cohort of patients and to compare patients with SFN to a group of patients without SFN to highlight potential factors associated with SFN. This study was observational, retrospective, and monocentric. All patients with symptoms of SFN who underwent skin biopsies with intraepidermal nerve density counts were included. Patients with a count lower than 5 percentiles were considered to be in the SFN group. Other patients were considered to be the control group. A total of 162 patients with SFN and 161 controls were included. No cause was identified for 108 patients (61.7%). The established causes were autoimmune diseases (9.1%), diabetes or glucose intolerance (8%), medication (4%), liver disease (3.4%), and monoclonal gammopathy of undetermined significance (2.9%). Current or former smokers were more numerous in the SFN group (26.5%) than in the control group (16.1%), while vitamin D amounts were significantly lower in the SFN group than in the control group. Hence, tobacco smoking and vitamin D deficiency might be new putative causes of SFN.

Dismantling the structural ageism of ‘ageing in place’ to ensure ‘ageing in the right place’

Dismantling the structural ageism of ‘ageing in place’ to ensure ‘ageing in the right place’

Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias.

Disturbances in the brain's capacity to meet its energy demand increase the risk of synaptic loss, neurodegeneration, and cognitive decline. Nutritional and metabolic interventions that target metabolic pathways combined with diagnostics to identify deficits in cerebral bioenergetics may therefore offer novel therapeutic potential for Alzheimer's disease (AD) prevention and management. Many diet-derived natural bioactive components can govern cellular energy metabolism but their effects on brain aging are not clear. This review examines how nutritional metabolism can regulate brain bioenergetics and mitigate AD risk. We focus on leading mechanisms of cerebral bioenergetic breakdown in the aging brain at the cellular level, as well as the putative causes and consequences of disturbed bioenergetics, particularly at the blood-brain barrier with implications for nutrient brain delivery and nutritional interventions. Novel therapeutic nutrition approaches including diet patterns are provided, integrating studies of the gut microbiome, neuroimaging, and other biomarkers to guide future personalized nutritional interventions.

HIV-1 genetic diversity and transmitted drug resistance to integrase strand transfer inhibitors among recently diagnosed adults in Porto Alegre, South Brazil.

The HIV-1 genetic diversity and the presence of transmitted drug resistance mutations (TDRMs) against integrase strand transfer inhibitors (INSTIs) were assessed sequencing samples of antiretroviral (ARV)-naive HIV-1-infected individuals from South Brazil. Viral RNA from 42 ART-naive individuals was submitted to complete HIV-1 integrase gene amplification by RT-PCR and sequencing. Viral strains carrying TDRMs against INSTIs were not detected in the present study. However, the polymorphisms L74M and L74I were each observed in 4.8% of the individuals. These accessory mutations have been reported as putative causes of TDRMs in ART with raltegravir, but only when associated with additional major mutations. When submitted to HIV-1 subtyping, 50% were classified as subtype C, 21% as recombinant BC, 19% as subtype B, 4.8% as subtype F1 and 4.8% as recombinant CF1. All 42 ARV-naive individuals were apparently susceptible to INSTIs, included in the Brazilian therapeutic guideline since 2009. To the best of our knowledge, this is the first study to evaluate TDRMs against INSTIs in Brazil. The most prevalent HIV-1 subtypes were subtype C, followed by the recombinant BC and subtype B, which is in agreement with previous studies. However, the presence of subtype F1 and recombinant CF1 reported herein was not observed in previous studies.

Smartphone-based behaviour analysis for challenging behaviour in intellectual and developmental disabilities and autism spectrum disorder - Study protocol for the ProVIA trial.

BackgroundChallenging behaviour (CB) comprises various forms of aggressive and problematic behaviours frequently occurring in children with intellectual and developmental disability (IDD) or autism spectrum disorder (ASD). CB often arises from impaired communication or problem solving skills. It is often met with coercive measure due to a lack of alternative strategies on the part of the caregiver, while it also impacts on the caregivers due to the exposure to physical harm and high levels of stress. Within the ProVIA project we developed a smartphone-based tool for caregivers of children with IDD and/or ASD to prevent and modify CB. The ProVIA app systematically helps caregivers to identify specific causes of CB and provides individualised practical guidance to prevent CB and consecutive coercive measures, thus aiming to improve the health and well-being of the children and caregivers.MethodsIn this uncontrolled open trial we will enrol N = 25 caregivers of children aged 3–11 years with a diagnosis of IDD and/or ASD. Participants will use the ProVIA-Kids app for 8 weeks. During the intervention phase, participants will conduct behaviour analyses after each instance of CB. The app will summarise the identified putative causes for the CB in each situation, and provide recommendations regarding the handling and prevention of CB. Furthermore, the app will aggregate data from all available behaviour analyses and identify the most relevant (i.e., most frequently reported) risk factors. Measurement points are at baseline (T0), after the intervention (T1) and 12 weeks after the end of the intervention (follow-up; T2). The primary outcome is the absolute change in parental stress (EBI total scale) between T0 and T1. Further aspects of interest are changes in CB severity and frequency, caregiver mood, satisfaction with the parenting role (EFB-K total scale) and experienced parenting competence (FKE total scale). Pre-post comparisons will be analysed with paired sample t-tests.DiscussionProVIA is pioneering structured behaviour analysis via smartphone, assessing predefined causes of CB and providing feedback and recommendations. If this approach proves successful, the ProVIA-Kids app will be a valuable tool for caregivers to prevent CB and improve their own as well as the children’s quality of life.Trial registrationThe study is registered at https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_IDDRKS00029039 (registered May 31, 2022).

Epidemic time series similarity is related to geographic distance and age structure.

ObjectiveMore similar locations may have similar infectious disease dynamics. There is clear overlap in putative causes for epidemic similarity, such as geographic distance, age structure, and population size. We compare the effects of these potential drivers on epidemic similarity compared to a baseline assumption that differences in the basic reproductive number (R0) will translate to differences in epidemic trajectories.MethodsUsing COVID-19 case counts from United States counties, we explore the importance of geographic distance, population size differences, and age structure dissimilarity on resulting epidemic similarity.ResultsWe find clear effects of geographic space, age structure, population size, and R0 on epidemic similarity, but notably the effect of age structure was stronger than the baseline assumption that differences in R0 would be most related to epidemic similarity.ConclusionsTogether, this highlights the role of spatial and demographic processes on SARS-CoV2 epidemics in the United States.

Cardiovascular complications of COVID-19.

Cardiac injury associated with coronavirus disease 2019 (COVID-19) is associated with high fatality rates. We reviewed the literature on COVID-19-related cardiovascular complications to elucidate the putative causes, diagnosis, and management of cardiovascular complications of COVID-19. Putative causes of these cardiovascular complications include cytokine storm, myocarditis, coronary plaque rupture, hypercoagulability, stress cardiomyopathy or combinations thereof. Cardiac troponin, D-dimer, and N-terminal pro B-type natriuretic peptide levels all provide prognostic information on COVID-19-related cardiovascular complications: elevated levels correlate with poorer prognosis. Coronary thrombosis due to COVID-19 may be associated with a higher thrombus burden than that from other causes. Hypercoagulability can be extremely challenging to treat, and in the absence of contra-indications, thromboprophylaxis is generally indicated in intensive care unit patients. With the exception of percutaneous coronary intervention for acute myocardial infarction, there are no specific treatments for COVID-19-related cardiovascular complications and management is primarily supportive. Whether antiviral therapies, coupled with monoclonal antibodies administered early in the course of COVID-19 illness will prevent severe cardiovascular complications remains to be seen.

Adverse childhood experiences: A scoping review of measures and methods

Adverse childhood experiences (ACEs) lead to excess morbidity and mortality. However, this evidence has not resulted in large-scale efforts to prevent ACEs. We conducted a scoping review of ACEs research to determine its direction and identify advancement toward solutions to prevent ACEs. The review was conducted using PRISMA guidelines. Articles were considered eligible for inclusion if they were empirical studies based on original quantitative data from humans published between 1999 and 2019 and used the term “adverse” or adversity” to refer to a construct under study or a specific measure in the methodology. After a comprehensive search across nine databases, screening of the abstracts of 3,944 articles and the full texts of 2,341 articles, 1,361 empirical articles met inclusion criteria. We coded year of publication; journal name; stated study purpose (e.g., descriptive, intervention); types of adversities used to define ACEs; funding sources and declared conflicts of interest; country of the sample; and affiliation with other studies. To characterize the extent to which ACEs research focuses on ACE prevention, we then coded “narratives” reflected in research goals, with a particular focus on whether this research focuses exclusively on ACEs as the primary predictor variables, or if it integrates “upstream” social determinants of health and health inequities that may lead to ACE exposure. Thus, we coded how the elements of the stated research goals related to ACEs (e.g., predictor, mediator, moderator, and outcome variables) using the World Health Organization’s framework on social determinants of health (Solar & Irwin, 2010). Finally, we coded whether protective factors were included in research designs and the level of these factors (e.g., individual vs. community), and researchers’ recommendations for translating their findings to action. All variables were coded by at least two coders; inter-rater reliabilities ranged from 79 to 100%. We found that 60.6% of articles were based on samples recruited from the U.S.; funding sources have shifted to U.S. institutions with biomedical or clinical concerns; that only 47.2% of articles included in their definition of ACEs all seven items from the original ACE study; and that the dominant narrative about ACEs started with ACEs as the “villains” who begin a story of decline and ended with “victims” who have behavioral and/or emotional problems. Studies overwhelmingly examined the downstream effects of ACEs rather than upstream causes or preventive interventions. That is, only 6.6% of articles proposed protective factors that went beyond the individual or family level; and researchers’ recommendations favored amelioration of ACEs after they occur, with only 20% of articles mentioning primordial or primary prevention. This disproportionate focus on downstream determinants after ACEs have already occurred limits the impact of this research in terms of potential cost-benefit, social justice, and mitigation of health inequities. We recommend that future ACEs research be incorporated into broader, strengths-based and action-oriented frameworks focused on social determinants of health and health inequities; link ACEs to their putative causes as a bridge to primordial/primary prevention; address obstacles to this shift toward upstream causes of ACEs; and communicate findings and recommendations more effectively.

Global assessment of shark strandings

AbstractMarine wildlife stranding is a global phenomenon, and for some taxonomic groups, these events are well monitored and documented. Although sharks are among the most threatened vertebrates, strandings have historically been neglected, with little information on this topic currently available. To address this knowledge gap, a systematic review on scientific publications from indexed databases, multimedia material and citizen science databases was performed. A total of 3150 reports were recovered, with strandings dating back to 1880 including 89 species of sharks from 22 families. Both single/small‐scale and mass stranding events were observed. Species ranged from coastal to oceanic, with reports for small‐, medium‐ and large‐sized sharks. Leopard (Triakis semifasciata, Triakidae), brown smooth‐hound (Mustelus henlei, Triakidae) and salmon sharks (Lamna ditropis, Laminidae) were the species with most records. Females stranded significantly more than males, but juveniles and adults were affected in the same proportion. Shark strandings were reported for 47 countries, and the United States was the most representative location, highlighting the states of California and Oregon. Survival rates were extremely low, indicating that stranded sharks are more vulnerable that other taxonomic groups. Potential and putative causes were identified, being similar to those suggested for marine mammal strandings. Our results indicate that although they occur to a lesser extent when compared to mammals, shark strandings are neglected, and urgent measurements are necessary to better understand, document and to properly respond to these events.

Mortality and causes of death among people with convulsive epilepsy in northwestern China

ObjectiveWe analyzed mortality and causes of death among people with convulsive epilepsy in rural areas of northwestern China. MethodsWe established a population-based prospective cohort of people with convulsive epilepsy in an epilepsy prevention and management program in rural northwestern China from January 2012 to December 2013. A uniform cause of death questionnaire was used to obtain detailed information on participants who died during the follow-up until December 2016. We calculated the standardized mortality ratios (SMRs) and proportional mortality rate for major causes of death. Cox proportional hazards regression analysis was used to investigate the risk factors associated with mortality. ResultsAmong 4296 people with convulsive epilepsy, 216 died during a median follow-up of 59 months. The overall mortality rate was 10.9 per 1000 person-years, and the overall SMR was 2.0. Accidents (25.5%) ranked first in the cause of death, followed by status epilepticus (SE) (22.9%), probable sudden unexpected death in epilepsy (SUDEP) (22.7%), cerebrovascular disease (13.0%), and cardiovascular disease (6.5%). Drowning (10.6%), motor vehicle accidents (13.6%), and falls (4.6%) were the major causes of death by accidents. Female participants had a reduced risk of death from accidents with the hazard ratio (HR) of 0.3 (95% confidence interval (CI): 0.1–0.6). A high risk of death from cerebrovascular disease (HR: 7.2; 95% CI: 2.1–23.6) was found in participants with an onset age of epilepsy older than 16 years. SignificanceThe risk of death from convulsive epilepsy in rural northwestern China is twice that of the general population. Accidents, SE, and SUDEP are the leading putative causes of death. Educating people with epilepsy in different regions may help reduce death-related events.

Taking care of a diarrhea epidemic in an urban hospital in Bangladesh: Appraisal of putative causes, presentation, management, and deaths averted.

BackgroundIn April 2018, a diarrhea epidemic broke out in Dhaka city and adjoining areas, which continued through May. The Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), a dedicated diarrheal disease hospital, had a large upsurge in patient visits during the epidemic. An enhanced understanding of the epidemiology of this epidemic may help health-related professionals better prepare for such events in the future. This study examined the microbial etiology and non-pathogen factors associated with diarrhea during the epidemic. The study also evaluated the patients’ presentation and clinical course and estimated the potential mortality averted by treating patients during the epidemic.Methodology/Principal findingsData from the patients who were treated at Dhaka Hospital during the diarrhea epidemic between April 2 and May 12, 2018 and were enrolled into the Diarrheal Disease Surveillance System (DDSS) at icddr,b were compared with the DDSS-enrolled patients treated during the seasonally-matched periods in the flanking years using logistic regression. icddr,b Dhaka Hospital treated 29,212 diarrheal patients during the 2018 epidemic period (and 25,950 patients per comparison period on average). Vibrio cholerae was the most common pathogen isolated (7,946 patients; 27%) and associated with diarrhea during the epidemic (adjusted odds ratio [AOR] 1.5, 95% CI: 1.1–2.0). The interaction of Vibrio cholerae with ETEC (AOR 2.7, 95% CI: 1.3–5.9) or Campylobacter (AOR 2.4, 95% CI: 1.1–5.1) was associated with further increased odds of diarrhea during the epidemic. In children under five years old, rotavirus was the most common pathogen (2,029 patients; 26%). Those who were adolescents (AOR 2.0, 95% CI: 1.3–3.1) and young adults (AOR 1.9, 95% CI: 1.4–2.5) compared to children younger than five years, resided within a 10 km radius of Dhaka Hospital (AOR 1.6, 95% CI: 1.1–2.2) compared to those living outside 20 km, borrowed money or relied on aid to pay for the transport to the hospital (AOR 1.6, 95% CI: 1.2–2.0), used tap water (AOR 1.8, 95% CI: 1.4–2.4) for drinking compared to tubewell water, and disposed of the solid waste directly outside the house (AOR 4.0, 95% CI: 2.7–5.9) were more likely to present with diarrhea during the epidemic. During the epidemic, patients were more likely to present with severe dehydration (odds ratio [OR] 1.6, 95% CI: 1.3–2.0) and require inpatient admission (OR 2.5, 95% CI: 1.9–3.3), intravenous rehydration (OR 1.7, 95% CI: 1.4–2.1), and antibiotics (OR 2.2, 95% CI: 1.8–2.7). The in-hospital case fatality rate was low (13 patients; 0.04%), and the hospital averted between 12,523 and 17,265 deaths during the epidemic.Conclusions/SignificanceVibrio cholerae played the primary role in the 2018 diarrhea epidemic in Dhaka. Campylobacter, enterotoxigenic Escherichia coli, and rotavirus had a secondary role. Adolescents and adults, residents of the metropolitan area, and those who were relatively poor and lacked safe water, sanitation, and hygiene (WASH) practices comprised the most vulnerable groups. Despite the increased disease severity during the epidemic, the case fatality rate was less than 0.1%. icddr,b Dhaka Hospital saved as many as 17,265 lives during the epidemic.

Early-life patterns of growth are linked to levels of phenotypic trait covariance and postfledging mortality across avian species.

Life history studies have established that trade‐offs between growth and survival are common both within and among species. Identifying the factor(s) that mediate this trade‐off has proven difficult, however, especially at the among‐species level. In this study, we examined a series of potentially interrelated traits in a community of temperate‐zone passerine birds to help understand the putative causes and consequences of variation in early‐life growth among species. First, we examined whether nest predation risk (a proven driver of interspecific variation in growth and development rates) was correlated with species‐level patterns of incubation duration and nestling period length. We then assessed whether proxies for growth rate covaried with mean trait covariance strength (i.e., phenotypic correlations ( rp), which can be a marker of early‐life stress) among body mass, tarsus length, and wing length at fledging. Finally, we examined whether trait covariance strength at fledging was related to postfledging survival. We found that higher nest predation risk was correlated with faster skeletal growth and that our proxies for growth corresponded with increased trait covariance strength ( rp), which subsequently, correlated with higher mortality in the next life stage (postfledging period). These results provide an indication that extrinsic pressures (nest predation) impact rates of growth, and that there are costs of rapid growth across species, expressed as higher mean rp and elevated postfledging mortality. The link between higher levels of trait covariance at fledging and increased mortality is unclear, but increased trait covariance strength may reflect reduced phenotypic flexibility (i.e., phenotypic canalization), which may limit an organism's capacity for coping with environmental or ecological variability.

Infectious spondylitis with pathology mimicking that of tuberculosis in a cervical vertebra of a plesiosaur from the Upper Cretaceous of Patagonia, Argentina

Paleopathological studies have been used to understand the history of injury and disease in extinct populations, their putative causes and, on this basis, to infer paleoecology and behavioral aspects. The most common pathologies reported in the zoological/paleontological record are traumatic injuries, post-traumatic malformations, inflammatory arthritis, infection and congenital defects. Although pathologies in plesiosaurs are recognized since the 1870s, reports of infectious disease are comparatively scarce. Here we report the pathological cervical vertebra of a plesiosaur recovered from the Upper Cretaceous of Argentina. The anterior external surface shows an elliptical, subchondral erosion with new bone formation and slight adjacent filigree reaction. The right anteroventral surface of the centrum bears erosive processes with bone reaction and alterations that have the appearance produced by space-occupied masses. On the left anteroventral surface of the centrum, there are abnormal vascular channels, associated with a groove just ventral to the articular surface. The combination of these features indicates that the pathological aspect of the vertebra is due to an infection. The pattern of bone abnormalities is compatible with those described in Pleistocene mammals affected by the granulomatous tuberculosis infection and with the abnormal ribs and cervical vertebrae of an eosauropterygian from the Triassic. The case reported herein represents the first record of tuberculosis-like infection in a plesiosaur. As the vertebra was not part of an associated skeleton, we cannot infer if the cause of death could have been related to the compromised hunting ability (due to limited neck mobility) or the result of infection-related organ failure.

Integrated genomic analyses of cutaneous T-cell lymphomas reveal the molecular bases for disease heterogeneity

AbstractCutaneous T-cell lymphomas (CTCLs) are a clinically heterogeneous collection of lymphomas of the skin-homing T cell. To identify molecular drivers of disease phenotypes, we assembled representative samples of CTCLs from patients with diverse disease subtypes and stages. Via DNA/RNA-sequencing, immunophenotyping, and ex vivo functional assays, we identified the landscape of putative driver genes, elucidated genetic relationships between CTCLs across disease stages, and inferred molecular subtypes in patients with stage-matched leukemic disease. Collectively, our analysis identified 86 putative driver genes, including 19 genes not previously implicated in this disease. Two mutations have never been described in any cancer. Functionally, multiple mutations augment T-cell receptor–dependent proliferation, highlighting the importance of this pathway in lymphomagenesis. To identify putative genetic causes of disease heterogeneity, we examined the distribution of driver genes across clinical cohorts. There are broad similarities across disease stages. Many driver genes are shared by mycosis fungoides (MF) and Sezary syndrome (SS). However, there are significantly more structural variants in leukemic disease, leading to highly recurrent deletions of putative tumor suppressors that are uncommon in early-stage skin-centered MF. For example, TP53 is deleted in 7% and 87% of MF and SS, respectively. In both human and mouse samples, PD1 mutations drive aggressive behavior. PD1 wild-type lymphomas show features of T-cell exhaustion. PD1 deletions are sufficient to reverse the exhaustion phenotype, promote a FOXM1-driven transcriptional signature, and predict significantly worse survival. Collectively, our findings clarify CTCL genetics and provide novel insights into pathways that drive diverse disease phenotypes.

P117 Patient perceptions about causes of flare in IBD: results from the baseline dataset of the PREdiCCt study

Abstract Background Patient reported outcomes are important endpoints in IBD management, but patient perceptions of the causes of disease flare are unknown and thus may reveal novel areas for future study. Methods The PREdiCCt study (https://www.predicct.co.uk) is the largest prospective study of the causes of IBD flare. 2629 patients in clinical remission were recruited from 48 UK sites and followed for 2 years with detailed assessment of environmental and dietary factors via monthly questionnaires. 1946 (74%) patients completed the baseline questionnaires. We present here the results of the baseline questionnaire analysis of patient perceptions of disease flare, derived from a list of 17 putative causes from the literature and their own experience via free text input. Results In total 1,946 IBD patients [male=852, CD=1000; UC/IBDU=946, age 45.8±15.5 (mean±SD in years)] gave their opinion about factors initiating a flare. The commonest causes reported were stress (n=1359, 69.8%), dietary changes (n=911, 46.8%), alcohol use (n=385, 19.8%), sleep disturbances (n=331, 17%) and that their medication stopped working (n=308, 15.8%) (Figure 1). CD participants were more likely to identify dietary changes (50% vs 43%, p<0.001) and menstruation (16% vs 10% of female patients, p<0.001) as flare triggers than UC/IBDU participants, while UC/IBDU participants more frequently reported loss of response to medication as a trigger for flare (9% vs 5% for CD participants, p<0.001). CD patients with small bowel involvement were more likely to name dietary changes (61% vs 42%, p<0.001), travel (14% vs 9%, p=0.016) and smoking (4% vs 1%, p=0.04) as flare triggers. When compared by gender, the ranking of causes was identical but female participants were more likely to identify stress (77% vs 65%, p<0.001) and antibiotic use (12% vs 6%, p<0.001) as reasons for disease relapse compared to male participants. Conclusion Stress, dietary changes and alcohol use were identified as the main causes of flare by patients with dietary changes more frequently reported in CD (especially those with small bowel involvement). The impact of environmental and dietary factors in the development of flare is being further investigated with ongoing longitudinal data collection in the PREdiCCt Study.

OP22 Factors independently associated with fatigue in IBD: Results from the baseline dataset of the PREdiCCt study

Abstract Background Fatigue is one of the most common symptoms in IBD resulting in decreased quality of life, impaired work productivity, and higher societal costs. However, little is known about its etiology and pathophysiology. We aimed to estimate the prevalence of fatigue and to identify predictive factors for fatigue. Methods The PREdiCCt study (https://www.predicct.co.uk) is the largest prospective study of the causes of IBD flare. 2629 patients in clinical remission were recruited from 48 UK sites. 1946 (74%) patients completed the baseline questionnaires. We assessed the prevalence of fatigue at baseline using a single item from the IBD Control questionnaire. To identify predictors for fatigue, we performed univariable and multivariable analyses including demographic, biochemical, environmental and psychosocial factors such as anxiety and depression [HADS], sleep quality [PSQI] and physical exercise [GPAQ]). Results 759/1919 IBD patients in clinical remission (39.6%) reported fatigue in the past 2 weeks, while 1034 patients (53.9%) did not report fatigue. Patients who reported fatigue were more frequently female, had more frequently CD, and were more frequently smokers (Table 1). Univariable comparisons showed higher inflammatory markers in the fatigued group, with fewer patients in clinical remission. Multivariable analyses identified female sex (OR 2.4), CRP>5 (OR 2.1), bad sleep quality (OR 2.5), anxiety (OR 1.8) and depression (OR 6.2) as independent factors associated with fatigue (Table 2). Conclusion We show the significant burden of fatigue in IBD patients and describe putative causes which demonstrate both the impact of residual gut inflammation and the relationship between fatigue and psychological well-being. The impact of environmental and dietary factors on fatigue is being further investigated with ongoing longitudinal data collection in the PREdiCCt study.

Observations on recent mass mortality events of marine mussels in the Oosterschelde, the Netherlands

Two mass mortality events (MMEs) of marine mussels that took place in the Oosterschelde, the Netherlands—the first in 2015/2016 and the second in 2019—both severely affected mussel production. The current study presents our observations on the onset and course of both MMEs and discusses probable putative causes. The two MMEs displayed a distinct course of events. The first event started in November 2015 with high mortality rates on culture plots, which remained elevated until the autumn of 2016. Approximately 40–50% of mussels from all age classes were lost on culture plots and 100% were lost from wild seed beds. The second event started in April–May 2019 and continued until the end of July, with mortality ranging from 20 to 100%, again from all age classes. Culture areas other than the Oosterschelde and other shellfish species were not affected. Histological and bacteriological screening produced no evidence for common pathogens or pollution as a primary mortality factor and there is no indication of abnormal environmental conditions preceding or during the events. We hypothesize that a cumulation of stressors results in weakening of the mussels and in elevated mortality rates. In 2019, this cumulation of stressors could be high spawning activities (an unusual high concentration of mussel larvae was found in April) that resulted in very low condition from April to June, a Phaeocystis bloom in April to May that prevented a quick recovery, and the development of granulocytomas that were found in up to 60 to 70% of live mussels as a consequence of cumulative stress. Although no (single) putative causes could be identified, this study contributes to the knowledge on MMEs in mussels and fits in a wider and disturbing trend on mortality events in shellfish.

AID in Chronic Lymphocytic Leukemia: Induction and Action During Disease Progression.

The enzyme activation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin (Ig) genes, critical actions for an effective adaptive immune response. However, in addition to the benefits generated by its physiological roles, AID is an etiological factor for the development of human and murine leukemias and lymphomas. This review highlights the pathological role of AID and the consequences of its actions on the development, progression, and therapeutic refractoriness of chronic lymphocytic leukemia (CLL) as a model disease for mature lymphoid malignancies. First, we summarize pertinent aspects of the expression and function of AID in normal B lymphocytes. Then, we assess putative causes for AID expression in leukemic cells emphasizing the role of an activated microenvironment. Thirdly, we discuss the role of AID in lymphomagenesis, in light of recent data obtained by NGS analyses on the genomic landscape of leukemia and lymphomas, concentrating on the frequency of AID signatures in these cancers and correlating previously described tumor-gene drivers with the presence of AID off-target mutations. Finally, we discuss how these changes could affect tumor suppressor and proto-oncogene targets and how they could be associated with disease progression. Collectively, we hope that these sections will help to better understand the complex paradox between the physiological role of AID in adaptive immunity and its potential causative activity in B-cell malignancies.

EFFECTS OF THE VERTICAL HETEROGENEITY OF WATER MASSES ON THE STABILITY OF INDUSTRIAL WATER SUPPLY IN INDUSTRY-INTENSIVE AREAS

The stability of water supply systems is one of the main factors for reliable operation of large industrial complexes. This problem is considered through the case of the Azot branch of JSC URALCHEM in the city of Berezniki, which derives raw process water from the Kama River (Kama storage reservoir). A characteristic feature of this water body is a highly variable hydrological regime. During the summer low water period, it is characterized by low current velocities. In winter, when the water level in the reservoir declines, a typical river flow regime is observed. In addition, the water body is exposed to heavy human impact. The bulk of the load comes from non-declared non-point (diffuse) sources. Their characteristic feature is high suspended solids content, and, accordingly, the density of the effluents. Their behavior is fundamentally different from the processes of dilution and migration of effluents with neutral buoyancy. Traditional methods of calculating dilution processes cannot be used to describe them. A two-layer flow is formed, where the content of basic ions in the surface horizon is more than an order of magnitude lower than near the bottom. Early in July 2020, a significant increase in the content of chlorine and sodium ions was observed at the water intake facility of the Azot branch, causing a shutdown of the plant. The causes of the phenomenon had to be identified. The putative causes were emergency discharges of concentrated waste from the sludge dump on the shore or contamination by the wastewater entering the Kama River below the intake facility due to backflow. These situations can be modeled taking into account the vertical heterogeneity of water masses based on the coupling of hydrodynamic models in one-, two-, and three-dimensional formulation. As a result, it was shown that the only cause of the emergency could be water intake from the Kama River bottom flow.

Comparison of 15 dinoflagellate genomes reveals extensive sequence and structural divergence in family Symbiodiniaceae and genus Symbiodinium

BackgroundDinoflagellates in the family Symbiodiniaceae are important photosynthetic symbionts in cnidarians (such as corals) and other coral reef organisms. Breakdown of the coral-dinoflagellate symbiosis due to environmental stress (i.e. coral bleaching) can lead to coral death and the potential collapse of reef ecosystems. However, evolution of Symbiodiniaceae genomes, and its implications for the coral, is little understood. Genome sequences of Symbiodiniaceae remain scarce due in part to their large genome sizes (1–5 Gbp) and idiosyncratic genome features.ResultsHere, we present de novo genome assemblies of seven members of the genus Symbiodinium, of which two are free-living, one is an opportunistic symbiont, and the remainder are mutualistic symbionts. Integrating other available data, we compare 15 dinoflagellate genomes revealing high sequence and structural divergence. Divergence among some Symbiodinium isolates is comparable to that among distinct genera of Symbiodiniaceae. We also recovered hundreds of gene families specific to each lineage, many of which encode unknown functions. An in-depth comparison between the genomes of the symbiotic Symbiodinium tridacnidorum (isolated from a coral) and the free-living Symbiodinium natans reveals a greater prevalence of transposable elements, genetic duplication, structural rearrangements, and pseudogenisation in the symbiotic species.ConclusionsOur results underscore the potential impact of lifestyle on lineage-specific gene-function innovation, genome divergence, and the diversification of Symbiodinium and Symbiodiniaceae. The divergent features we report, and their putative causes, may also apply to other microbial eukaryotes that have undergone symbiotic phases in their evolutionary history.