A proportion of subjects with internal derangements of the temporomandibular joint (TMJ) may have a central sensitization disorder that may affect pain perception after surgery. This study aims to ...estimate the association between fibromyalgianess (FMness) score, a summed score of the Widespread Pain Index (WPI) and Symptom Severity Sore (SSS), and outcomes following TMJ arthroscopy.
A retrospective cohort study including individuals who received arthroscopy for TMJ internal derangement at Michigan Medicine between 2011 and 2020 was performed. A predictor variable, FMness score, was assigned via the sum of WPI and SSS. Univariate and bivariate analyses were performed. Linear-mixed effects models were used to analyze 6 different outcomes, each in their own model: pain, jaw functional limitation scale (JFLS), JFLS-mobility domain, pain-related disability, comfortable maximum interincisal opening, and active maximum interincisal opening. Covariance structure was selected based on null model fit separately for each outcome.
Thirty-one subjects were included in the study sample. Twenty-eight subjects were female. Average age was 45.9 years. Bivariate analysis demonstrated that subject's FMness score was not correlated with pain (b = 0.03 −0.10, 0.17 P = .59) or JFLS score (b = 1.00 −.80, 2.81 P = .27). However, subject's FMness score was significant for predicting JFLS-mobility domain score (b = .61, 0.05, 1.18 P = .04).
A greater extent of central sensitization was associated with lower comfortable mouth opening after surgery, greater limitations in opening wide enough to eat various foods (higher JFLS-mobility scores), and higher pain-related disability. Future studies with larger sample sizes and reconstructive TMJ operations such as total TMJ arthroplasty may help clarify the impact of SSS and WPI scores on outcomes of TMJ surgery.
AbstractObjectiveTo assess the association between learning disability and risk of hospital admission and death from covid-19 in England among adults and children.DesignPopulation based cohort study ...on behalf of NHS England using the OpenSAFELY platform.SettingPatient level data were obtained for more than 17 million people registered with a general practice in England that uses TPP software. Electronic health records were linked with death data from the Office for National Statistics and hospital admission data from NHS Secondary Uses Service.ParticipantsAdults (aged 16-105 years) and children (<16 years) from two cohorts: wave 1 (registered with a TPP practice as of 1 March 2020 and followed until 31 August 2020); and wave 2 (registered 1 September 2020 and followed until 8 February 2021). The main exposure group consisted of people on a general practice learning disability register; a subgroup was defined as those having profound or severe learning disability. People with Down’s syndrome and cerebral palsy were identified (whether or not they were on the learning disability register).Main outcome measureCovid-19 related hospital admission and covid-19 related death. Non-covid-19 deaths were also explored.ResultsFor wave 1, 14 312 023 adults aged ≥16 years were included, and 90 307 (0.63%) were on the learning disability register. Among adults on the register, 538 (0.6%) had a covid-19 related hospital admission; there were 222 (0.25%) covid-19 related deaths and 602 (0.7%) non-covid deaths. Among adults not on the register, 29 781 (0.2%) had a covid-19 related hospital admission; there were 13 737 (0.1%) covid-19 related deaths and 69 837 (0.5%) non-covid deaths. Wave 1 hazard ratios for adults on the learning disability register (adjusted for age, sex, ethnicity, and geographical location) were 5.3 (95% confidence interval 4.9 to 5.8) for covid-19 related hospital admission and 8.2 (7.2 to 9.4) for covid-19 related death. Wave 2 produced similar estimates. Associations were stronger among those classified as having severe to profound learning disability, and among those in residential care. For both waves, Down’s syndrome and cerebral palsy were associated with increased hazards for both events; Down’s syndrome to a greater extent. Hazard ratios for non-covid deaths followed similar patterns with weaker associations. Similar patterns of increased relative risk were seen for children, but covid-19 related deaths and hospital admissions were rare, reflecting low event rates among children.ConclusionsPeople with learning disability have markedly increased risks of hospital admission and death from covid-19, over and above the risks observed for non-covid causes of death. Prompt access to covid-19 testing and healthcare is warranted for this vulnerable group, and prioritisation for covid-19 vaccination and other targeted preventive measures should be considered.
How food production first entered eastern Africa ~5000 years ago and the extent to which people moved with livestock is unclear. We present genome-wide data from 41 individuals associated with Later ...Stone Age, Pastoral Neolithic (PN), and Iron Age contexts in what are now Kenya and Tanzania to examine the genetic impacts of the spreads of herding and farming. Our results support a multiphase model in which admixture between northeastern African-related peoples and eastern African foragers formed multiple pastoralist groups, including a genetically homogeneous PN cluster. Additional admixture with northeastern and western African-related groups occurred by the Iron Age. These findings support several movements of food producers while rejecting models of minimal admixture with foragers and of genetic differentiation between makers of distinct PN artifacts.
Situated at over 5,000 meters above sea level in the Himalayan Mountains, Roopkund Lake is home to the scattered skeletal remains of several hundred individuals of unknown origin. We report ...genome-wide ancient DNA for 38 skeletons from Roopkund Lake, and find that they cluster into three distinct groups. A group of 23 individuals have ancestry that falls within the range of variation of present-day South Asians. A further 14 have ancestry typical of the eastern Mediterranean. We also identify one individual with Southeast Asian-related ancestry. Radiocarbon dating indicates that these remains were not deposited simultaneously. Instead, all of the individuals with South Asian-related ancestry date to ~800 CE (but with evidence of being deposited in more than one event), while all other individuals date to ~1800 CE. These differences are also reflected in stable isotope measurements, which reveal a distinct dietary profile for the two main groups.
The nuclear factor κB (NF-κB) transcription factor regulates cellular stress responses and the immune response to infection. NF-κB activation results in oscillations in nuclear NF-κB abundance. To ...define the function of these oscillations, we treated cells with repeated short pulses of tumor necrosis factor-α at various intervals to mimic pulsatile inflammatory signals. At all pulse intervals that were analyzed, we observed synchronous cycles of NF-κB nuclear translocation. Lower frequency stimulations gave repeated full-amplitude translocations, whereas higher frequency pulses gave reduced translocation, indicating a failure to reset. Deterministic and stochastic mathematical models predicted how negative feedback loops regulate both the resetting of the system and cellular heterogeneity. Altering the stimulation intervals gave different patterns of NF-κB-dependent gene expression, which supports the idea that oscillation frequency has a functional role.
There are many unanswered questions about the population history of the Central and South Central Andes, particularly regarding the impact of large-scale societies, such as the Moche, Wari, Tiwanaku, ...and Inca. We assembled genome-wide data on 89 individuals dating from ∼9,000-500 years ago (BP), with a particular focus on the period of the rise and fall of state societies. Today’s genetic structure began to develop by 5,800 BP, followed by bi-directional gene flow between the North and South Highlands, and between the Highlands and Coast. We detect minimal admixture among neighboring groups between ∼2,000–500 BP, although we do detect cosmopolitanism (people of diverse ancestries living side-by-side) in the heartlands of the Tiwanaku and Inca polities. We also highlight cases of long-range mobility connecting the Andes to Argentina and the Northwest Andes to the Amazon Basin.
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•Ancient DNA transect reveals north-south substructure of Andean highlands by 5,800 BP•After 5,800 BP, gene flow mixed highland people with their neighbors•After 2,000 BP, striking genetic continuity through rise and fall of major cultures
Genome-wide data from 89 ancient humans illuminates the changes to the genetic landscape in the Central Andes over 9,000 years, revealing large-scale gene flow and cosmopolitan societies in the Tiwanaku and Inca polities.
The transition to agriculture occurred relatively late in Eastern Europe, leading researchers to debate whether it was a gradual, interactive process or a colonisation event. In the forest and ...forest-steppe regions of Ukraine, farming appeared during the fifth millennium BCE, associated with the Cucuteni-Trypillia cultural complex (CTCC, ~ 5000-3000 BCE). Across Europe, the Neolithisation process was highly variable across space and over time. Here, we investigate the population dynamics of early agriculturalists from the eastern forest-steppe region based on the analyses of 20 ancient genomes from the site of Verteba Cave (3935-825 cal BCE). Results reveal that the CTCC individuals' ancestry is related to both western hunter-gatherers and Near Eastern farmers, has no local ancestry associated with Ukrainian Neolithic hunter-gatherers and has steppe ancestry. An Early Bronze Age individual has an ancestry profile related to the Yamnaya expansions but with 20% of ancestry related to the other Trypillian individuals, which suggests admixture between the Trypillians and the incoming populations carrying steppe-related ancestry. A Late Bronze Age individual dated to 980-825 cal BCE has a genetic profile indicating affinity to Beaker-related populations, detected close to 1000 years after the end of the Bell Beaker phenomenon during the third millennium BCE.
Two teosintes made modern maize Yang, Ning; Wang, Yuebin; Liu, Xiangguo ...
Science (American Association for the Advancement of Science),
12/2023, Volume:
382, Issue:
6674
Journal Article
Peer reviewed
Open access
The origins of maize were the topic of vigorous debate for nearly a century, but neither the current genetic model nor earlier archaeological models account for the totality of available data, and ...recent work has highlighted the potential contribution of a wild relative,
ssp.
. Our population genetic analysis reveals that the origin of modern maize can be traced to an admixture between ancient maize and
ssp.
in the highlands of Mexico some 4000 years after domestication began. We show that variation in admixture is a key component of maize diversity, both at individual loci and for additive genetic variation underlying agronomic traits. Our results clarify the origin of modern maize and raise new questions about the anthropogenic mechanisms underlying dispersal throughout the Americas.
ObjectivesTo assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform.MethodsWe ...conducted two cohort studies from 1 March to 14 June 2020. Working on behalf of National Health Service England, we used routine clinical data in England linked to death data. In study 1, we identified people with an NSAID prescription in the last 3 years from the general population. In study 2, we identified people with rheumatoid arthritis/osteoarthritis. We defined exposure as current NSAID prescription within the 4 months before 1 March 2020. We used Cox regression to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region.ResultsIn study 1, we included 536 423 current NSAID users and 1 927 284 non-users in the general population. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, we included 1 708 781 people with rheumatoid arthritis/osteoarthritis, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, we observed a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with current use of NSAID versus non-use.ConclusionsWe found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.
AbstractObjectiveTo compare the effectiveness of sotrovimab (a neutralising monoclonal antibody) with molnupiravir (an antiviral) in preventing severe outcomes of covid-19 in adult patients infected ...with SARS-CoV-2 in the community and at high risk of severe outcomes from covid-19.DesignObservational cohort study with the OpenSAFELY platform.SettingWith the approval of NHS England, a real world cohort study was conducted with the OpenSAFELY-TPP platform (a secure, transparent, open source software platform for analysis of NHS electronic health records), and patient level electronic health record data were obtained from 24 million people registered with a general practice in England that uses TPP software. The primary care data were securely linked with data on SARS-CoV-2 infection and treatments, hospital admission, and death, over a period when both drug treatments were frequently prescribed in community settings.ParticipantsAdult patients with covid-19 in the community at high risk of severe outcomes from covid-19, treated with sotrovimab or molnupiravir from 16 December 2021.InterventionsSotrovimab or molnupiravir given in the community by covid-19 medicine delivery units.Main outcome measuresAdmission to hospital with covid-19 (ie, with covid-19 as the primary diagnosis) or death from covid-19 (ie, with covid-19 as the underlying or contributing cause of death) within 28 days of the start of treatment.ResultsBetween 16 December 2021 and 10 February 2022, 3331 and 2689 patients were treated with sotrovimab and molnupiravir, respectively, with no substantial differences in baseline characteristics. Mean age of all 6020 patients was 52 (standard deviation 16) years; 59% were women, 89% were white, and 88% had received three or more covid-19 vaccinations. Within 28 days of the start of treatment, 87 (1.4%) patients were admitted to hospital or died of infection from SARS-CoV-2 (32 treated with sotrovimab and 55 with molnupiravir). Cox proportional hazards models stratified by area showed that after adjusting for demographic information, high risk cohort categories, vaccination status, calendar time, body mass index, and other comorbidities, treatment with sotrovimab was associated with a substantially lower risk than treatment with molnupiravir (hazard ratio 0.54, 95% confidence interval 0.33 to 0.88, P=0.01). Consistent results were found from propensity score weighted Cox models (0.50, 0.31 to 0.81, P=0.005) and when restricted to people who were fully vaccinated (0.53, 0.31 to 0.90, P=0.02). No substantial effect modifications by other characteristics were detected (all P values for interaction >0.10). The findings were similar in an exploratory analysis of patients treated between 16 February and 1 May 2022 when omicron BA.2 was the predominant variant in England.ConclusionsIn routine care of adult patients in England with covid-19 in the community, at high risk of severe outcomes from covid-19, those who received sotrovimab were at lower risk of severe outcomes of covid-19 than those treated with molnupiravir.
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