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Background and purpose: The objective was to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on European clinical autonomic practice. Methods: Eighty-four neurology-driven or interdisciplinary autonomic centers in 22 European countries were invited to fill in a web-based survey between September and November 2021. Results: Forty-six centers completed the survey (55%). During the first pandemic year, the number of performed tilt-table tests, autonomic outpatient and inpatient visits decreased respectively by 50%, 45% and 53%, and every third center reported major adverse events due to postponed examinations or visits. The most frequent newly diagnosed or worsened cardiovascular autonomic disorders after COVID-19 infection included postural orthostatic tachycardia syndrome, orthostatic hypotension and recurrent vasovagal syncope, deemed to be likely related to the infection by ≥50% of the responders. Forty-seven percent of the responders also reported about people with new onset of orthostatic intolerance but negative tilt-table findings, and 16% about people with psychogenic pseudosyncope after COVID-19. Most patients were treated non-pharmacologically and symptomatic recovery at follow-up was observed in ≥45% of cases. By contrast, low frequencies of newly diagnosed cardiovascular autonomic disorders following COVID-19 vaccination were reported, most frequently postural orthostatic tachycardia syndrome and recurrent vasovagal syncope, and most of the responders judged a causal association unlikely. Non-pharmacological measures were the preferred treatment choice, with 50%–100% recovery rates at follow-up. Conclusions: Cardiovascular autonomic disorders may develop or worsen following a COVID-19 infection, whilst the association with COVID-19 vaccines remains controversial. Despite the severe pandemic impact on European clinical autonomic practice, a specialized diagnostic work-up was pivotal to identify non-autonomic disorders in people with post-COVID-19 orthostatic complaints.

Objective: To assess the performance of a multimodal seizure detection device, first tested in adults (sensitivity 86%, PPV 49%), in a pediatric cohort living at home or residential care. Methods: In this multicenter, prospective, video-controlled cohort-study, nocturnal seizures were detected by heartrate and movement changes in children with epilepsy and intellectual disability. Participants with a history of >1 monthly major motor seizure wore Nightwatch bracelet at night for 3 months. Major seizures were defined as tonic–clonic, generalized tonic >30 s, hyperkinetic, or clusters (>30 min) of short myoclonic or tonic seizures. The video of all events (alarms and nurse diaries) and about 10% of whole nights were reviewed to classify major seizures, and minor or no seizures. Results: Twenty-three participants with focal or generalized epilepsy and nightly motor seizures were evaluated during 1511 nights, with 1710 major seizures. First 1014 nights, 4189 alarms occurred with average of 1.44/h, showing average sensitivity of 79.9% (median 75.4%) with mean PPV of 26.7% (median 11.1%) and false alarm rate of 0.2/hour. Over 90% of false alarms in children was due to heart rate (HR) part of the detection algorithm. To improve this rate, an adaptation was made such that the alarm was only triggered when the wearer was in horizontal position. For the remaining 497 nights, this was tested prospectively, 384 major seizures occurred. This resulted in mean PPV of 55.5% (median 58.1%) and a false alarm rate 0.08/h while maintaining a comparable mean sensitivity of 79.4% (median 93.2%). Significance: Seizure detection devices that are used in bed which depend on heartrate and movement show similar sensitivity in children and adults. However, children do show general higher false alarm rate, mostly triggered while awake. By correcting for body position, the false alarms can be limited to a level that comes close to that in adults.

Jujube is a nutritious fruit, and is high in vitamin C, fiber, phenolics, flavonoids, nucleotides, and organic acids. It is both an important food and a source of traditional medicine. Metabolomics can reveal metabolic differences between Ziziphus jujuba fruits from different jujube cultivars and growth sites. In the fall of 2022, mature fresh fruit of eleven cultivars from replicated trials at three sites in New Mexico—Leyendecker, Los Lunas, and Alcalde—were sampled from September to October for an untargeted metabolomics study. The 11 cultivars were Alcalde 1, Dongzao, Jinsi (JS), Jinkuiwang (JKW), Jixin, Kongfucui (KFC), Lang, Li, Maya, Shanxi Li, and Zaocuiwang (ZCW). Based on the LC–MS/MS analysis, there were 1315 compounds detected with amino acids and derivatives (20.15%) and flavonoids (15.44%) as dominant categories. The results reveal that the cultivar was the dominant factor in metabolite profiles, while the location was secondary. A pairwise comparison of cultivar metabolomes revealed that two pairs had fewer differential metabolites (i.e., Li/Shanxi Li and JS/JKW) than all the other pairs, highlighting that pairwise metabolic comparison can be applied for cultivar fingerprinting. Differential metabolite analysis also showed that half of drying cultivars have up-regulated lipid metabolites compared to fresh or multi-purpose fruit cultivars and that specialized metabolites vary significantly between cultivars from 35.3% (Dongzao/ZCW) to 56.7% (Jixin/KFC). An exemplary analyte matching sedative cyclopeptide alkaloid sanjoinine A was only detected in the Jinsi and Jinkuiwang cultivars. Overall, our metabolic analysis of the jujube cultivar’s mature fruits provides the largest resource of jujube fruit metabolomes to date and will inform cultivar selection for nutritional and medicinal research and for fruit metabolic breeding.

Over the last decades public discussion of opioids has changed radically. Opioid was once a word largely restricted to professional medical and pharmacological use for the treatment and management of pain. But propelled by the rapidly growing international wave of opioid use and overuse, it is now part of a much wider public discussion that covers more than pain medicine: dependency, addiction, over-prescription and oversupply, recreational drug use, and criminal drug trafficking. The word opioid is now controversial and value-laden. A key component of the developing views and values about opioids is carried by language, both written and spoken: on radio and television, in the social media, but also between healthcare professionals and patients, where communicating about pain in a context of emotionally and value-charged images of opioids can be challenging. This paper analyses aspects of the language of opioids. We document the shift from medical to addiction meanings and uses in the key term opioid, together with narcotic, drug, heroin, and to a lesser degree opiate and morphine. These changes follow four chronological phases in attitudes to pain and its treatment: traditional medical approaches to pain; pain being recognised as an under-treated ‘fifth vital sign’; the pharmacological and medical promotion of opioid use for treating pain, especially chronic pain; and the current reaction where opioid has become a pejorative and emotive term, closely connected to words like epidemic and addiction. We investigate whether and how a less charged and more balanced discourse might be possible.

Real-time carbon monitoring of wastewater using bio-electrochemical sensors coupled with advanced data analysis methods provides WRRFs with an opportunity for efficient wastewater quality monitoring and an early warning tool for plant upsets.

Sustainable sanitation and resource recovery technologies are needed to address rapid environmental and socioeconomic changes. Research prioritization is critical to expedite the development and deployment of such technologies across their vast system space (e.g., technology choices, design and operating decisions). In this study, we introduce QSDsan - an open-source tool written in Python (under the object-oriented programming paradigm) and developed for the quantitative sustainable design (QSD) of sanitation and resource recovery systems. As an integrated platform for system design, process modeling and simulation, techno-economic analysis (TEA), and life cycle assessment (LCA), QSDsan can be used to enumerate and investigate the opportunity space for emerging technologies under uncertainty, while considering contextual parameters that are critical to technology deployment. We illustrate the core capabilities of QSDsan through two distinct examples: (i) evaluation of a complete sanitation value chain that compares three alternative systems; and (ii) dynamic simulation of the wastewater treatment plant described in the benchmark simulation model no. 1 (BSM1). Through these examples, we show the utility of QSDsan to automate design, enable flexible process modeling, achieve rapid and reproducible simulations, and to perform advanced statistical analyses with integrated visualization. We strive to make QSDsan a community-led platform with online documentation, tutorials (explanatory notes, executable scripts, and video demonstrations), and a growing ecosystem of supporting packages (e.g., DMsan for decision-making). This platform can be freely accessed, used, and expanded by researchers, practitioners, and the public alike, ultimately contributing to the advancement of safe and affordable sanitation technologies around the globe.

Objective: A substantial number of patients with a transient loss of consciousness (T-LOC) are referred to a tertiary syncope unit without a diagnosis. This study investigates the final diagnoses reached in patients who, on referral, were undiagnosed or inaccurately diagnosed in secondary care. Methods: This study is an in-depth analysis of the recently published Fainting Assessment Study II, a prospective cohort study in a tertiary syncope unit. The diagnosis at the tertiary syncope unit was established after history taking (phase 1), following autonomic function tests (phase 2), and confirming after critical follow-up of 1.5–2 years, with the adjudicated diagnosis (phase 3) by a multidisciplinary committee. Diagnoses suggested by the referring physician were considered the phase 0 diagnosis. We determined the accuracy of the phase 0 diagnosis by comparing this with the phase 3 diagnosis. Results: 51% (134/264) of patients had no diagnosis upon referral (phase 0), the remaining 49% (130/264) carried a diagnosis, but 80% (104/130) considered their condition unexplained. Of the patients undiagnosed at referral, three major causes of T-LOC were revealed: reflex syncope (69%), initial orthostatic hypotension (20%) and psychogenic pseudosyncope (13%) (sum > 100% due to cases with multiple causes). Referral diagnoses were either inaccurate or incomplete in 65% of the patients and were mainly altered at tertiary care assessment to reflex syncope, initial orthostatic hypotension or psychogenic pseudosyncope. A diagnosis of cardiac syncope at referral proved wrong in 17/18 patients. Conclusions: Syncope patients diagnosed or undiagnosed in primary and secondary care and referred to a syncope unit mostly suffer from reflex syncope, initial orthostatic hypotension or psychogenic pseudosyncope. These causes of T-LOC do not necessarily require ancillary tests, but can be diagnosed by careful history-taking. Besides access to a network of specialized syncope units, simple interventions, such as guideline-based structured evaluation, proper risk-stratification and critical follow-up may reduce diagnostic delay and improve diagnostic accuracy for syncope.

SummaryObjectiveGuidelines suggest considering antiseizure medication (ASM) discontinuation in patients with epilepsy who become seizure-free. Little is known about how discontinuation decisions are being made in practice. We measured the frequency of, and factors associated with, discussions and decisions surrounding ASM discontinuation.MethodsWe performed a multicenter retrospective cohort study at the University of Michigan (UM) and two Dutch centers: Wilhelmina Children’s Hospital (WCH) and Stichting Epilepsie Instellingen Nederland (SEIN). We screened all children and adults with outpatient epilepsy visits in January 2015 and included those with at least one visit during the subsequent two years where they were seizure-free for at least one year. We recorded whether charts documented 1) a discussion with the patient about possible ASM discontinuation and 2) any planned attempt to discontinue at least one ASM. We conducted multilevel logistic regressions to determine factors associated with each outcome.ResultsWe included 1,058 visits from 463 patients. Of all patients who were seizure-free at least one year, 248/463 (53%) had documentation of any discussion and 98/463 (21%) planned to discontinue at least one ASM. Corresponding frequencies for patients who were seizure-free at least two years were 184/285 (65%) and 74/285 (26%). The probability of discussing or discontinuing increased with longer duration of seizure-freedom. Still, even for patients who were ten years seizure-free, our models predicated that in only 49% of visits was a discontinuation discussion documented, and in only 16% of visits was it decided to discontinue all ASMs. Provider-to-provider variation explained 18% of variation in whether patients discontinued any ASM.SignificanceOnly approximately half of patients with prolonged seizure-freedom had a documented discussion about ASM discontinuation. Discontinuation was fairly rare even among low-risk patients. Future work should further explore barriers to and facilitators of counseling and discontinuation attempts.Key points boxWe performed a multicenter cohort study evaluating factors associated with discussions and decisions to discontinue antiseizure medications (ASMs).Of all patients seizure-free at least one year, 53% had documentation of any discussion and 21% planned to discontinue at least one ASM. Corresponding frequencies for patients seizure-free at least two years were 65% and 26%.While discussions and discontinuations increased with increasing seizure-free interval, even for patients who were ten years seizure-free, in only 49% of visits did providers discuss the possibility of discontinuation, and in only 16% of visits did patients decide to discontinue all ASMs.Provider-to-provider variation explained 18% of variation in whether patients discontinued any ASM.ASM discontinuation was fairly rare even among low-risk patients. Future work should further explore barriers to and facilitators of counseling and discontinuation attempts, including the role that differences in physician counseling play in determining whether patients discontinue.

Orthostatic hypotension (OH) is an established and common cardiovascular risk factor for falls. An in-depth understanding of the various interacting pathophysiological pathways contributing to OH-related falls is essential to guide improvements in diagnostic and treatment opportunities. We applied systems thinking to multidisciplinary map out causal mechanisms and risk factors. For this, we used group model building (GMB) to develop a causal loop diagram (CLD). The GMB was based on the input of experts from multiple domains related to OH and falls and all proposed mechanisms were supported by scientific literature. Our CLD is a conceptual representation of factors involved in OH-related falls, and their interrelatedness. Network analysis and feedback loops were applied to analyze and interpret the CLD, and quantitatively summarize the function and relative importance of the variables. Our CLD contains 50 variables distributed over three intrinsic domains (cerebral, cardiovascular, and musculoskeletal), and an extrinsic domain (e.g., medications). Between the variables, 181 connections and 65 feedback loops were identified. Decreased cerebral blood flow, low blood pressure, impaired baroreflex activity, and physical inactivity were identified as key factors involved in OH-related falls, based on their high centralities. Our CLD reflects the multifactorial pathophysiology of OH-related falls. It enables us to identify key elements, suggesting their potential for new diagnostic and treatment approaches in fall prevention. The interactive online CLD renders it suitable for both research and educational purposes and this CLD is the first step in the development of a computational model for simulating the effects of risk factors on falls.

Epileptic networks are intimately connected with the autonomic nervous system, as exemplified by a plethora of ictal (during a seizure) autonomic manifestations, including epigastric sensations, palpitations, goosebumps and syncope (fainting). Ictal autonomic changes might serve as diagnostic clues, provide targets for seizure detection and help us to understand the mechanisms that underlie sudden unexpected death in epilepsy (SUDEP). Autonomic alterations are generally more prominent in focal seizures originating from the temporal lobe, demonstrating the importance of limbic structures to the autonomic nervous system, and are particularly pronounced in focal-to-bilateral and generalized tonic–clonic seizures. The presence, type and severity of autonomic features are determined by the seizure onset zone, propagation pathways, lateralization and timing of the seizures, and the presence of interictal autonomic dysfunction. Evidence is mounting that not all autonomic manifestations are linked to SUDEP. In addition, experimental and clinical data emphasize the heterogeneity of SUDEP and its infrequent overlap with sudden cardiac death. Here, we review the spectrum and diagnostic value of the mostly benign and self-limiting autonomic manifestations of epilepsy. In particular, we focus on presentations that are likely to contribute to SUDEP and discuss how wearable devices might help to prevent SUDEP. The close connection between epileptic networks and the autonomic nervous system is illustrated by a range of autonomic manifestations during a seizure. This article reviews the spectrum and diagnostic value of these manifestations, focusing on presentations that could contribute to sudden unexpected death in epilepsy.

PURPOSE: We performed an economic evaluation, from a societal perspective, to examine the cost-utility and cost-effectiveness of a wearable multimodal seizure detection device: NightWatch.METHODS: We collected data between November 2018 and June 2020 from the PROMISE trial (NCT03909984), including children aged 4-16 years with refractory epilepsy living at home. Caregivers completed questionnaires on stress, quality of life, health care consumption and productivity costs after two-month baseline and two-month intervention with NightWatch. We used costs, stress levels and quality-adjusted life years (QALYs) to calculate incremental cost-effectiveness ratios (ICERs). Missing items were handled by mean imputation. Sensitivity analyses were performed to examine the robustness of the results including bootstrap sampling.RESULTS: We included 41 children (44% female; mean age 9.8 years, standard deviation (SD) 3.7 years). Total societal costs of the baseline period (T1) were on average €3,238 per patient, whereas after intervention (T2) this reduced to 2,463 (saving €775). The QALYs were similar between both periods (mean QALY 0.90 per participant, SD at T1 0.10, SD at T2 0.13). At a ceiling ratio of €50.000, NightWatch showed a 72% cost-effective probability. Univariate sensitivity analyses, on the perspective and imputation method, demonstrated result robustness.CONCLUSION: Our study suggests that NightWatch might be a cost-effective addition to current standard care for children with refractory epilepsy living at home. Further research with an additional target group for a large timeframe may support the findings of this research.

Shea butter is an important lipid material for food, cosmetic, and pharmaceutical industries. Most of the shea butter consumed in the world comes from Africa. The extraction protocol is not standardized among all regions of production. It can be done using either traditional or improved (semi-mechanical) processes. The quality of shea butter and its composition depend on multiple factors such as the edaphic parameters, morphology and harvesting method of the fruits, and treatment applied to fruits, nuts, and kernels, respectively. In this paper, all traditional and improved extraction processes reported, including the enormous possible variants, were reviewed and summarized. Several optimal conditions have been defined for both the traditional and the modern processes. Nevertheless, we are far from process harmonization, and therefore from the best conditions of shea butter processing. The screw press extraction was the most widely used among the modern processes due to its yield of butter extraction of about 82%. Microwave-assisted extraction gave the highest butter yield, 88%, and traditional shea butter extraction was about 20–35%.

Background and purpose: Disorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries. The aim of this study was to identify neurology-driven or interdisciplinary clinical ANS laboratories in Europe, describe their characteristics and explore regional differences. ------ Methods: We contacted the European national ANS and neurological societies, as well as members of our professional network, to identify clinical ANS laboratories in each country and invite them to answer a web-based survey. ----- Results: We identified 84 laboratories in 22 countries and 46 (55%) answered the survey. All laboratories perform cardiovascular autonomic function tests, and 83% also perform sweat tests. Testing for catecholamines and autoantibodies are performed in 63% and 56% of laboratories, and epidermal nerve fiber density analysis in 63%. Each laboratory is staffed by a median of two consultants, one resident, one technician and one nurse. The median (interquartile range [IQR]) number of head-up tilt tests/laboratory/year is 105 (49-251). Reflex syncope and neurogenic orthostatic hypotension are the most frequently diagnosed cardiovascular ANS disorders. Thirty-five centers (76%) have an ANS outpatient clinic, with a median (IQR) of 200 (100-360) outpatient visits/year; 42 centers (91%) also offer inpatient care (median 20 [IQR 4-110] inpatient stays/year). Forty-one laboratories (89%) are involved in research activities. We observed a significant difference in the geographical distribution of ANS services among European regions: 11 out of 12 countries from North/West Europe have at least one ANS laboratory versus 11 out of 21 from South/East/Greater Europe (p = 0.021). ----- Conclusions: This survey highlights disparities in the availability of healthcare services for people with ANS disorders across European countries, stressing the need for improved access to specialized care in South, East and Greater Europe.

The investigators examined predictors of treatment response to anger self-management training (ASMT) among patients with chronic moderate-severe traumatic brain injury (TBI).A multicenter randomized clinical trial comprising 90 participants with moderate-severe TBI was conducted. Fifty-four participants who were randomly assigned to receive active treatment and provided complete data were included in the current secondary analysis. Model averaging was used to examine the relative importance and significance of pretreatment variables for predicting change during treatment. Dependent variables were pre- to posttreatment changes in trait anger (TA) and anger expression-out (AX-O) subscale scores of the State-Trait Anger Expression Inventory-Revised. Predictors included demographic, injury-related, and neuropsychological variables, including both objective and self-reported measures of executive function, as well as readiness to change and participation of a significant other in treatment.Change in both dependent variables was predicted by higher baseline anger. Greater change in TA was additionally predicted by White race, higher education, shorter posttraumatic amnesia, and worse self-reported (but not objectively measured) executive dysfunction; the latter predictor may have indicated better self-awareness. Greater change in AX-O was additionally predicted by better episodic memory and, paradoxically, lower readiness to change.Further research should focus on adapting psychoeducational anger treatments to better serve the diverse populations affected by moderate-severe TBI. These findings suggest that providing memory aids to support the use of learned strategies after treatment cessation would be beneficial. Further research should also examine the construct of readiness to change and specific aspects of executive function that may affect treatment response in psychoeducational treatments. These findings were derived from only one model of anger intervention, and the relevance to other treatment approaches cannot be assumed.

Smartphones offer unique opportunities to trace the convoluted behavioral patterns accompanying healthy aging. Here we captured smartphone touchscreen interactions from a healthy population (N = 684, ∼309 million interactions) spanning 16 to 86 years of age and trained a decision tree regression model to estimate chronological age based on the interactions. The interactions were clustered according to their next interval dynamics to quantify diverse smartphone behaviors. The regression model well-estimated the chronological age in health (mean absolute error = 6 years, R2 = 0.8). We next deployed this model on a population of stroke survivors (N = 41) to find larger prediction errors such that the estimated age was advanced by 6 years. A similar pattern was observed in people with epilepsy (N = 51), with prediction errors advanced by 10 years. The smartphone behavioral model trained in health can be used to study altered aging in neurological diseases.

Disorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries. The aim of this study was to identify neurology-driven or interdisciplinary clinical ANS laboratories in Europe, describe their characteristics and explore regional differences.We contacted the European national ANS and neurological societies, as well as members of our professional network, to identify clinical ANS laboratories in each country and invite them to answer a web-based survey.We identified 84 laboratories in 22 countries and 46 (55%) answered the survey. All laboratories perform cardiovascular autonomic function tests, and 83% also perform sweat tests. Testing for catecholamines and autoantibodies are performed in 63% and 56% of laboratories, and epidermal nerve fiber density analysis in 63%. Each laboratory is staffed by a median of two consultants, one resident, one technician and one nurse. The median (interquartile range [IQR]) number of head-up tilt tests/laboratory/year is 105 (49-251). Reflex syncope and neurogenic orthostatic hypotension are the most frequently diagnosed cardiovascular ANS disorders. Thirty-five centers (76%) have an ANS outpatient clinic, with a median (IQR) of 200 (100-360) outpatient visits/year; 42 centers (91%) also offer inpatient care (median 20 [IQR 4-110] inpatient stays/year). Forty-one laboratories (89%) are involved in research activities. We observed a significant difference in the geographical distribution of ANS services among European regions: 11 out of 12 countries from North/West Europe have at least one ANS laboratory versus 11 out of 21 from South/East/Greater Europe (p = 0.021).This survey highlights disparities in the availability of healthcare services for people with ANS disorders across European countries, stressing the need for improved access to specialized care in South, East and Greater Europe.

Even though raw mass spectrometry data is information rich, the vast majority of the data is underutilized. The ability to interrogate these rich datasets is handicapped by the limited capability and flexibility of existing software. We introduce the Mass Spec Query Language (MassQL) that addresses these issues by enabling an expressive set of mass spectrometry patterns to be queried directly from raw data. MassQL is an open-source mass spectrometry query language for flexible and mass spectrometer manufacturer-independent mining of MS data. We envision the flexibility, scalability, and ease of use of MassQL will empower the mass spectrometry community to take fuller advantage of their mass spectrometry data and accelerate discoveries.

BACKGROUND: Cardioinhibition may diminish with age, but the changing balance of cardioinhibition and vasodepression with age has not been quantified, leaving the mechanism of vasovagal syncope (VVS) in old age unclear .OBJECTIVES: This study sought to quantify age-related changes of vasodepression and cardioinhibition in tilt-induced VVS. METHODS: We studied 163 cases of tilt-induced WS, evoked using the Italian protocol with blood pressure, heart rate, and video-etectroencephalographic monitoring. Presyncope was excluded. Cardioinhibition was defined as the heart rate decrease before syncope; asystotic pauses (>= 3 seconds) were divided into early and late asystole, ie, beginning early enough to or too late to be the major cause of toss of consciousness. The log-ratio method was used to quantify contributions of cardioinhibition and vasodepression, assessed in 2 10-second periods before the onset of cardioinhibition and before syncope. RESULTS: With increasing age, cardioinhibition decreased, ie, heart rate decreased less and more slowly near syncope (P < 0.0001), white vasodepression increased. Asystotic pauses were less frequent in the older one-half of the group than the younger one-half (26% vs 57%; P < 0.00001), but when it did, late asystole occurred more often (58% vs 15%; P < 0.001). CONCLUSIONS: The shift toward less cardioinhibition and more vasodepression with increased age probably reflects a physiological shift in circulatory control. The weakening of cardioinhibition with age may detract from the efficacy of pacing in older patients with VVS. Cardioinhibition-vasodepression balance should be considered in pacing decisions in older subjects with VVS. (C) 2022 by the American College of Cardiology Foundation.

Interactions between bacteria and phytoplankton can influence primary production, community composition, and algal bloom development. However, these interactions are poorly described for many consortia, particularly for freshwater bloom-forming cyanobacteria. Here, we assessed the gene content and expression of two uncultivated Acidobacteria from Lake Erie Microcystis blooms. These organisms were targeted because they were previously identified as important catalase producers in Microcystis blooms, suggesting that they protect Microcystis from H(2)O(2). Metatranscriptomics revealed that both Acidobacteria transcribed genes for uptake of organic compounds that are known cyanobacterial products and exudates, including lactate, glycolate, amino acids, peptides, and cobalamins. Expressed genes for amino acid metabolism and peptide transport and degradation suggest that use of amino acids and peptides by Acidobacteria may regenerate nitrogen for cyanobacteria and other organisms. The Acidobacteria genomes lacked genes for biosynthesis of cobalamins but expressed genes for its transport and remodeling. This indicates that the Acidobacteria obtained cobalamins externally, potentially from Microcystis, which has a complete gene repertoire for pseudocobalamin biosynthesis; expressed them in field samples; and produced pseudocobalamin in axenic culture. Both Acidobacteria were detected in Microcystis blooms worldwide. Together, the data support the hypotheses that uncultured and previously unidentified Acidobacteria taxa exchange metabolites with phytoplankton during harmful cyanobacterial blooms and influence nitrogen available to phytoplankton. Thus, novel Acidobacteria may play a role in cyanobacterial physiology and bloom development. IMPORTANCE Interactions between heterotrophic bacteria and phytoplankton influence competition and successions between phytoplankton taxa, thereby influencing ecosystem-wide processes such as carbon cycling and algal bloom development. The cyanobacterium Microcystis forms harmful blooms in freshwaters worldwide and grows in buoyant colonies that harbor other bacteria in their phycospheres. Bacteria in the phycosphere and in the surrounding community likely influence Microcystis physiology and ecology and thus the development of freshwater harmful cyanobacterial blooms. However, the impacts and mechanisms of interaction between bacteria and Microcystis are not fully understood. This study explores the mechanisms of interaction between Microcystis and uncultured members of its phycosphere in situ with population genome resolution to investigate the cooccurrence of Microcystis and freshwater Acidobacteria in blooms worldwide.

Orthostatic hypotension is an unusually large decrease in blood pressure on standing that increases the risk of adverse outcomes even when asymptomatic. Improvements in haemodynamic profiling with continuous blood pressure measurements have uncovered four major subtypes: initial orthostatic hypotension, delayed blood pressure recovery, classic orthostatic hypotension, and delayed orthostatic hypotension. Clinical presentations are varied and range from cognitive slowing with hypotensive unawareness or unexplained falls to classic presyncope and syncope. Establishing whether symptoms are due to orthostatic hypotension requires careful history taking, a thorough physical examination, and supine and upright blood pressure measurements. Management and prognosis vary according to the underlying cause, with the main distinction being whether orthostatic hypotension is neurogenic or non-neurogenic. Neurogenic orthostatic hypotension might be the earliest clinical manifestation of Parkinson's disease or related synucleinopathies, and often coincides with supine hypertension. The emerging variety of clinical presentations advocates a stepwise, individualised, and primarily non-pharmacological approach to the management of orthostatic hypotension. Such an approach could include the cessation of blood pressure lowering drugs, adoption of lifestyle measures (eg, counterpressure manoeuvres), and treatment with pharmacological agents in selected cases.

Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. The genetic causes of CFM remain largely unknown.We performed genome sequencing and linkage analysis in patients and families with microtia and CFM of unknown genetic etiology. The functional consequences of damaging missense variants were evaluated through expression of wild-type and mutant proteins in vitro.We studied a 5-generation kindred with microtia, identifying a missense variant in FOXI3 (p.Arg236Trp) as the cause of disease (logarithm of the odds = 3.33). We subsequently identified 6 individuals from 3 additional kindreds with microtia-CFM spectrum phenotypes harboring damaging variants in FOXI3, a regulator of ectodermal and neural crest development. Missense variants in the nuclear localization sequence were identified in cases with isolated microtia with aural atresia and found to affect subcellular localization of FOXI3. Loss of function variants were found in patients with microtia and mandibular hypoplasia (CFM), suggesting dosage sensitivity of FOXI3.Damaging variants in FOXI3 are the second most frequent genetic cause of CFM, causing 1% of all cases, including 13% of familial cases in our cohort.

Background Osteoporosis and low bone density (LBD) may be associated with higher risk of hearing loss, but findings are inconsistent and longitudinal data are scarce. Bisphosphonates may influence risk, but the relation has not been studied in humans. We longitudinally investigated associations of osteoporosis and LBD, bisphosphonate use, vertebral fracture (VF), hip fracture (HF), and risk of self-reported moderate or worse hearing loss. Design Longitudinal cohort study. Setting The Nurses' Health Study (NHS) (1982-2016) and Nurses' Health Study II (NHS II) (1995-2017). Participants Participants included 60,821 NHS women, aged 36-61 years at baseline, and 83,078 NHS II women, aged 31-48 years at baseline (total n = 143,899). Measurements Information on osteoporosis, LBD, bisphosphonate use, VF, HF, and hearing status was obtained from validated biennial questionnaires. In a subcohort (n = 3749), objective hearing thresholds were obtained by audiometry. Multivariable-adjusted Cox proportional hazards models were used to examine independent associations between osteoporosis (NHS), osteoporosis/LBD (NHS II), and risk of hearing loss. Results The multivariable-adjusted relative risk (MVRR, 95% confidence interval) of moderate or worse hearing loss was higher among women with osteoporosis or LBD in both cohorts. In NHS, compared with women without osteoporosis, the MVRR was 1.14 (1.09, 1.19) among women with osteoporosis; in NHS II, the MVRR was 1.30 (1.21, 1.40) among women with osteoporosis/LBD. The magnitude of the elevated risk was similar among women who did and did not use bisphosphonates. VF was associated with higher risk (NHS: 1.31 [1.16, 1.49]; NHS II: 1.39 [1.13, 1.71]), but HF was not (NHS: 1.00 [0.86, 1.16];NHS II: 1.15 [0.75,1.74]). Among participants with audiometric measurements, compared with women without osteoporosis/LBD, the mean multivariable-adjusted hearing thresholds were higher (i.e., worse) among those with osteoporosis/LBD who used bisphosphonates. Conclusion Osteoporosis and LBD may be important contributors to aging-related hearing loss. Among women with osteoporosis, the risk of hearing loss was not influenced by bisphosphonate use.

An expert committee was formed to reach consensus on the use of tilt table testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when other provocative cardiovascular autonomic tests are needed. While TTT adds to history taking, it cannot be a substitute for it. An abnormal TTT result is most meaningful if the provoked event is recognised by patients or eyewitnesses as similar to spontaneous events. The minimum requirements to perform TTT are a tilt table, a continuous beat-to-beat blood pressure monitor, at least one ECG lead, protocols for the indications stated below and trained staff. This basic equipment lends itself to the performance of (1) additional provocation tests, such as the active standing test, carotid sinus massage and autonomic function tests; (2) additional measurements, such as video, EEG, transcranial Doppler, NIRS, end-tidal CO2 or neuro-endocrine tests; and (3) tailor-made provocation procedures in those with a specific and consistent trigger of TLOC. TTT and other provocative cardiovascular autonomic tests are indicated if the initial evaluation does not yield a definite or highly likely diagnosis, but raises a suspicion of (1) reflex syncope, (2) the three forms of orthostatic hypotension (OH), i.e. initial, classic and delayed OH, as well as delayed orthostatic blood pressure recovery, (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT is to teach patients with reflex syncope and OH to recognise hypotensive symptoms and to perform physical counter manoeuvres.

Electrochemical disinfection—a method in which chemical oxidants are generated in situ via redox reactions on the surface of an electrode—has attracted increased attention in recent years as an alternative to traditional chemical dosing disinfection methods. Because electrochemical disinfection does not entail the transport and storage of hazardous materials and can be scaled across centralized and distributed treatment contexts, it shows promise for use both in resource limited settings and as a supplement for aging centralized systems. In this Critical Review, we explore the significance of treatment context, oxidant selection, and operating practice on electrochemical disinfection system performance. We analyze the impacts of water composition on oxidant demand and required disinfectant dose across drinking water, centralized wastewater, and distributed wastewater treatment contexts for both free chlorine- and hydroxyl-radical-based systems. Drivers of energy consumption during oxidant generation are identified, and the energetic performance of experimentally reported electrochemical disinfection systems are evaluated against optimal modeled performance. We also highlight promising applications and operational strategies for electrochemical disinfection and propose reporting standards for future work.

Struvite (MgNH4PO4·6H2O), a low water solubility (

Anthropogenic discharge of excess phosphorus (P) to water bodies and increasingly stringent discharge limits have fostered interest in quantifying opportunities for P recovery and reuse. To date, geospatial estimates of P recovery potential in the United States (US) have used human and livestock population data, which do not capture the engineering constraints of P removal from centralized water resource recovery facilities (WRRFs) and corn ethanol biorefineries where P is concentrated in coproduct animal feeds. Here, renewable P (rP) estimates from plant-wide process models were used to create a geospatial inventory of recovery potential for centralized WRRFs and biorefineries, revealing that individual corn ethanol biorefineries can generate on average 3 orders of magnitude more rP than WRRFs per site, and all corn ethanol biorefineries can generate nearly double the total rP of WRRFs across the US. The Midwestern states that make up the Corn Belt have the largest potential for P recovery and reuse from both corn biorefineries and WRRFs with a high degree of co-location with agricultural P consumption, indicating the untapped potential for a circular P economy in this globally significant grain-producing region.

Microtia is a congenital malformation that encompasses mild hypoplasia to complete loss of the external ear, or pinna. Although the contribution of genetic variation and environmental factors to microtia remains elusive, Amerindigenous populations have the highest reported incidence. Here, using both transmission disequilibrium tests and association studies in microtia trios (parents and affected child) and microtia cohorts enrolled in Latin America, we map an ∼10-kb microtia locus (odds ratio = 4.7; P = 6.78e-18) to the intergenic region between Roundabout 1 (ROBO1) and Roundabout 2 (ROBO2) (chr3: 78546526 to 78555137). While alleles at the microtia locus significantly increase the risk of microtia, their penetrance is low (1%). We demonstrate that the microtia locus contains a polymorphic complex repeat element that is expanded in affected individuals. The locus is located near a chromatin loop region that regulates ROBO1 and ROBO2 expression in induced pluripotent stem cell–derived neural crest cells. Furthermore, we use single nuclear RNA sequencing to demonstrate ROBO1 and ROBO2 expression in both fibroblasts and chondrocytes of the mature human pinna. Because the microtia allele is enriched in Amerindigenous populations and is shared by some East Asian subjects with craniofacial malformations, we propose that both populations share a mutation that arose in a common ancestor prior to the ancient migration of Eurasian populations into the Americas and that the high incidence of microtia among Amerindigenous populations reflects the population bottleneck that occurred during the migration out of Eurasia.

Although transient loss of consciousness (TLOC) is a common problem, hospital care for patients with TLOC is characterised by high rates of no diagnosis and misdiagnosis, accompanied by unnecessary hospital admissions and tests. We attribute these problems to increasing specialisation as well as to a blind spot for vasovagal syncope, a condition not claimed by any specialty. We suggest that all doctors seeing patients with TLOC, both in primary and secondary care, should be familiar with the presentations of the relatively harmless vasovagal syncope and the alarm symptoms of potentially life-threatening cardiac syncope. In this article we present some practical pointers to recognise these conditions and answer some frequently-asked questions regarding the diagnosis and treatment of TLOC.

Background and ObjectivesA recent Food and Drug Administration warning concerning an arrhythmogenic potential of lamotrigine created concern in the neurologic community. This warning was based on in vitro studies, but no clinically relevant risk was considered. This rapid systematic review aims to elucidate the risk of lamotrigine on sudden death or ECG abnormalities.MethodsWe conducted a systematic search of Ovid Medline and Ovid Embase, including randomized controlled trials and observational studies and studies of people with or without epilepsy, with the outcome measures sudden unexpected death in epilepsy (SUDEP) or sudden cardiac death as well as the development or worsening of ECG abnormalities. We evaluated the sudden death definitions used in all included studies, as some could have used unclear or overlapping definitions. We used the American Academy of Neurology risk of bias tool to evaluate the class of evidence and the GRADE approach to evaluate our confidence in the evidence.ResultsWe included 26 studies with 24,962 participants, of whom 2,326 used lamotrigine. Twelve studies showed no significant risk of SUDEP for lamotrigine users. One study reporting on sudden cardiac death and 3 studies with unclear sudden death definitions did not report an elevated risk of death in lamotrigine users compared to controls. In 10 studies reporting on ECG measures, there was no statistically significant increased risk among lamotrigine users except in 2 studies. These 2 studies reported either “slight increases” in PR interval or an increased PQ interval that the primary study authors believed to be related to structural cardiac differences rather than an effect of lamotrigine. One study was rated Class II; all others were Class III or IV. We had very low confidence in the evidence following the GRADE assessment. None of the studies examined the risk of lamotrigine in people with preexisting cardiac conditions.DiscussionThere is insufficient evidence to support or refute that lamotrigine is associated with sudden death or ECG changes in people with or without epilepsy as compared to antiseizure medication or placebo, due to the high risk of bias in most studies and low precision and inconsistency in the reported results.

Moroidin is a bicyclic plant octapeptide with tryptophan side-chain cross-links, originally isolated as a pain-causing agent from the Australian stinging tree

Omni Processors (OPs) are community-scale systems for non-sewered fecal sludge treatment. These systems have demonstrated their capacity to treat excreta from tens of thousands of people using thermal treatment processes (e.g., pyrolysis), but their relative sustainability is unclear. In this study, QSDsan (an open-source Python package) was used to characterize the financial viability and environmental implications of fecal sludge treatment via pyrolysis-based OP technology treating mixed and source-separated human excreta and to elucidate the key drivers of system sustainability. Overall, the daily per capita cost for the treatment of mixed excreta (pit latrines) via the OP was estimated to be 0.05 [0.03-0.08] USD·cap

Een recente waarschuwing van de US Food and Drug Administration (FDA) aangaande het gebruik van lamotrigine (Lamictal®) heeft veel stof doen opwaaien. De FDA waarschuwt voor het optreden van ritmestoornissen bij gebruik van lamotrigine door mensen met een geleidingsstoornis of andere cardiale comorbiditeiten. In deze bijdrage worden de achtergronden van de waarschuwing besproken en adviezen gegeven voor de praktijk.

Purpose: To determine the burden of non-epilepsy drugs on people with epilepsy, using administrative health care data. Methods: The Achmea Health Insurance Database (AHID) contains health claims data from 25 % of the Dutch population. From the AHID, we selected all policyholders with coverage for at least one full calendar year between 2006−2009. We included adults with diagnostic codes for epilepsy and randomly selected two frequency-matched controls per case. We labeled drugs dispensed at least twice per calendar year as chronic and excluded antiseizure medications. We estimated and compared the prevalence of chronic medication use, number of chronic medications used, number of prescriptions dispensed, Rx Risk comorbidity index, and drug burden index (DBI) between people with epilepsy and controls. Results: Non-epilepsy chronic medication use was more frequent in people with epilepsy than controls (67 % versus 59 %, p < 0.001). People with epilepsy had an increased DBI (average 0.19 versus 0.10, p < 0.001), used more chronic medications (median 2 versus 1, p < 0.001) and had more prescriptions dispensed (median 7 versus 3, p < 0.001). The DBI and number of unique chronic medications were higher among older (>60 years) than younger (

Sanitation remains a global challenge, both in terms of access to toilet facilities and resource intensity (e.g., energy consumption) of waste treatment. Overcoming barriers to universal sanitation coverage and sustainable resource management requires approaches that manage bodily excreta within coupled human and natural systems. In recent years, numerous analytical methods have been developed to understand cross-disciplinary constraints, opportunities, and trade-offs around sanitation and resource recovery. However, without a shared language or conceptual framework, efforts from individual disciplines or geographic contexts may remain isolated, preventing the accumulation of generalized knowledge. Here, we develop a version of the social-ecological systems framework modified for the specific characteristics of bodily excreta. This framework offers a shared vision for sanitation as a human-derived resource system, where people are part of the resource cycle. Through sanitation technologies and management strategies, resources including water, organics, and nutrients accumulate, transform, and impact human experiences and natural environments. Within the framework, we establish a multitiered lexicon of variables, characterized by breadth and depth, to support harmonized understanding and development of models and analytical approaches. This framework's refinement and use will guide interdisciplinary study around sanitation to identify guiding principles for sanitation that advance sustainable development at the nature-society interface.

Oral antiretroviral agents provide life-saving treatments for millions of people living with HIV, and can prevent new infections via pre-exposure prophylaxis1–5. However, some people living with HIV who are heavily treatment-experienced have limited or no treatment options, owing to multidrug resistance6. In addition, suboptimal adherence to oral daily regimens can negatively affect the outcome of treatment—which contributes to virologic failure, resistance generation and viral transmission—as well as of pre-exposure prophylaxis, leading to new infections1,2,4,7–9. Long-acting agents from new antiretroviral classes can provide much-needed treatment options for people living with HIV who are heavily treatment-experienced, and additionally can improve adherence10. Here we describe GS-6207, a small molecule that disrupts the functions of HIV capsid protein and is amenable to long-acting therapy owing to its high potency, low in vivo systemic clearance and slow release kinetics from the subcutaneous injection site. Drawing on X-ray crystallographic information, we designed GS-6207 to bind tightly at a conserved interface between capsid protein monomers, where it interferes with capsid-protein-mediated interactions between proteins that are essential for multiple phases of the viral replication cycle. GS-6207 exhibits antiviral activity at picomolar concentrations against all subtypes of HIV-1 that we tested, and shows high synergy and no cross-resistance with approved antiretroviral drugs. In phase-1 clinical studies, monotherapy with a single subcutaneous dose of GS-6207 (450 mg) resulted in a mean log10-transformed reduction of plasma viral load of 2.2 after 9 days, and showed sustained plasma exposure at antivirally active concentrations for more than 6 months. These results provide clinical validation for therapies that target the functions of HIV capsid protein, and demonstrate the potential of GS-6207 as a long-acting agent to treat or prevent infection with HIV. The small molecule GS-6207, which disrupts the function of the HIV capsid protein, shows potential as a long-acting therapeutic agent for the treatment and prevention of HIV infection.

The sixth Sustainable Development Goal seeks to achieve universal sanitation, but a lack of progress due to inhibiting factors (e.g., limitations in financial resources, sociocultural conditions, household decision-making) demands innovative approaches to meet this ambitious goal. Resource recovery may generate income to offset sanitation costs while also enhancing agriculture through increased access to agricultural nutrients. The objective of this work was to determine if resource recovery sanitation can be a profitable business model in a specific context (Kampala, Uganda) and to explore the potential for this approach to translate to other Sub-Saharan African contexts. A techno-economic analysis was performed to evaluate the financial viability of two nutrient recovery systems and business models in urban communities in Kampala under two financing scenarios: (1) Startup relying on partial sanitation aid, and (2) Self-sustaining without philanthropic financing. Results show profitability can be achieved at a nutrient selling price at or below fertilizer market value in Uganda. Recoverable nutrients from the total population without at least basic sanitation services, in 10 Sub-Saharan African countries, are the same magnitude as nutrients distributed in subsidy programs (30-450% of distributed nutrients), indicating a potential to offset inorganic fertilizer consumption or increase nutrient availability. This research makes a case to support innovative sanitation strategies and the development and financial support of human-derived fertilizer markets in areas with poor fertilizer and sanitation access.

It is a controversial issue that the difference of the occurrence of heterotopic ossification (HO) concerning cervical prosthesis is still huge. In this study, in the two cervical disc prostheses the development of HO is independent on their architecture., Study Design. Retrospective analysis using data from randomized clinical trials. Objective. To compare the occurrence of heterotopic ossification (HO) between two cervical disc prostheses. Clinical outcome and range of motion (ROM) were also evaluated. Summary of Background Data. Cervical arthroplasty was reported to be able to maintain the segmental ROM. However, controversy exists since the difference of the occurrence of HO concerning cervical prosthesis is still huge. Methods. Patients who underwent anterior cervical discectomy with arthroplasty for a cervical radiculopathy due to a herniated disc from the The Netherlands Cervical Kinematics (NECK) trial (activC; metal endplates with a polyethylene inlay and a keel for primary stability) and the PROCON trial (Bryan; metal-on-polymer with titanium coated endplates without a keel) were analyzed for HO at 12 and 24 months postoperatively. HO was scored according to the McAfee–Mehren classification. Segmental ROM was defined by a custom developed image analysis tool, and global cervical ROM was measured by Cobb's angle. Clinical outcome was evaluated by means of the neck disability index (NDI) as well as physical-component summary (PCS) and mental-component summary (MCS). Results. At 2-year follow-up, the occurrence of HO was 68% in patients treated with the activC prosthesis (severe HO 55%), which was comparable with 85% (P = 0.12) in patients with the Bryan disc (severe HO 44%; P = 0.43). The HO progression was similar between groups. Clinically, the patients had comparable NDI, PCS, and MCS at 2-year follow-up, and comparable improvement of clinical outcomes. The global ROM in the Bryan group (56.4 ± 10.8°) was significantly higher than in the activC group (49.5 ± 14.0, P = 0.044) at 2-year follow-up. Conclusion. In comparison of two cervical disc prostheses the development of HO is independent on their architecture. Although global ROM was higher in the Bryan prosthesis group, this difference was not deemed clinically important, particularly because the clinical condition of patients with and without severe HO was comparable. Level of Evidence: 2

Objectives We ascertained the prevalence of ictal arrhythmias to explain the high rate of sudden unexpected death in epilepsy (SUDEP) in Dravet syndrome (DS). Methods We selected cases with clinical DS, ≥6 years, SCN1A mutation, and ≥1 seizure/week. Home‐based ECG recordings were performed for 20 days continuously. Cases were matched for age and sex to two epilepsy controls with no DS and ≥1 major motor seizure during video‐EEG. We determined the prevalence of peri‐ictal asystole, bradycardia, QTc changes, and effects of convulsive seizures (CS) on heart rate, heart rate variability (HRV), and PR/QRS. Generalized estimating equations were used to account for multiple seizures within subjects, seizure type, and sleep/wakefulness. Results We included 59 cases. Ictal recordings were obtained in 45 cases and compared to 90 controls. We analyzed 547 seizures in DS (300 CS) and 169 in controls (120 CS). No asystole occurred. Postictal bradycardia was more common in controls (n = 11, 6.5%) than cases (n = 4, 0.7%; P = 0.002). Peri‐ictal QTc‐lengthening (≥60ms) occurred more frequently in DS (n = 64, 12%) than controls (n = 8, 4.7%, P = 0.048); pathologically prolonged QTc was rare (once in each group). In DS, interictal HRV was lower compared to controls (RMSSD P = 0.029); peri‐ictal values did not differ between the groups. Prolonged QRS/PR was rare and more common in controls (QRS: one vs. none; PR: three vs. one). Interpretation We did not identify major arrhythmias in DS which can directly explain high SUDEP rates. Peri‐ictal QTc‐lengthening was, however, more common in DS. This may reflect unstable repolarization and an increased propensity for arrhythmias.

The economic viability of corn biorefineries depends heavily on the sale of coproducts as animal feeds, but elevated phosphorus (P) contents can exacerbate manure management issues. Phosphorus removal from light steep water and thin stillage, two concentrated in-process aqueous streams at wet milling and dry-grind corn biorefineries, could simultaneously generate concentrated fertilizer and low-P animal feeds, but little is known regarding how differences in stream composition affect removal. To address this data gap, we show that the solubility of P in light steep filtrate (LSF) and thin stillage filtrate (TSF) exhibits distinct sensitivity to calcium (Ca) and base addition due to differences in P fractionation and protein abundance. In LSF, P was primarily organic, and near-complete removal of P (96%) was observed at pH 8 and a Ca/total P (TP) ratio of 2. In TSF, TP removal was lower (81%), and there was more equal distribution of organic and orthophosphate, indicating that the Ca requirements of inorganic P precipitation were a limiting factor. The C/H/N ratio, elemental characterization, and crude protein analysis of the precipitated solids indicated that coprecipitation of amorphous solids containing Ca, Mg, and K with soluble proteins facilitated removal of P, particularly in LSF. Although the removal mechanisms and solubility limits differed, these results highlighted the magnitude (40-70 mM) and efficacy (80-96%) of P recovery from two biorefinery streams.

Purpose Cervical spine surgery may affect sagittal alignment parameters and induce accelerated degeneration of the cervical spine. Cervical sagittal alignment parameters of surgical patients will be correlated with radiological adjacent segment degeneration (ASD) and with clinical outcome parameters. Methods Patients were analysed from two randomized, double-blinded trials comparing anterior cervical discectomy with arthroplasty (ACDA), with intervertebral cage (ACDF) and without intervertebral cage (ACD). C2–C7 lordosis, T1 slope, C2–C7 sagittal vertical axis (SVA) and the occipito-cervical angle (OCI) were determined as cervical sagittal alignment parameters. Radiological ASD was scored by the combination of decrease in disc height and anterior osteophyte formation. Neck disability index (NDI), SF-36 PCS and MCS were evaluated as clinical outcomes. Results The cervical sagittal alignment parameters were comparable between the three treatment groups, both at baseline and at 2-year follow-up. Irrespective of surgical method, C2–C7 lordosis was found to increase from 11° to 13°, but the other parameters remained stable during follow-up. Only the OCI was demonstrated to be associated with the presence and positive progression of radiological ASD, both at baseline and at 2-year follow-up. NDI, SF-36 PCS and MCS were demonstrated not to be correlated with cervical sagittal alignment. Likewise, a correlation with the value or change of the OCI was absent. Conclusion OCI, an important factor to maintain horizontal gaze, was demonstrated to be associated with radiological ASD, suggesting that the occipito-cervical angle influences accelerated cervical degeneration. Since OCI did not change after surgery, degeneration of the cervical spine may be predicted by the value of OCI. NECK trial Dutch Trial Register Number NTR1289. PROCON trial Trial Register Number ISRCTN41681847. Graphic abstract These slides can be retrieved under Electronic Supplementary Material.