Using three-dimensional digital models to establish alveolar morphotype

Background: The aim of the study was to propose a classification of alveolar morphotype and assess a relationship between extraction/non-extraction orthodontic treatment and changes to the alveolar process.Materials and methods: Seventy-five subjects (mean age = 23.2, SD = 5.1) were selected. Areas of the sections of the alveolar process (ASAP) at three different levels (0, 2, and 4 mm) were measured on pre- and post-treatment three-dimensional digital models. Method reliability was analysed using Dahlberg’s formula, intraclass correlation coefficient, and paired t-tests.Results: The mean ASAP was smallest at level 0 and largest at level 4. Pre-treatment ASAP < 773 mm2, < 863.9 mm2, and < 881.1 mm2 at levels 0, 2, and 4 mm, respectively, should be described as a “thin” alveolar morphotype. Regression models showed that pre-treatment ASAP was a predictor of the change of the alveolus during treatment only at level 2.Conclusions: Patients for whom pre-treatment ASAP is < 773 mm2, < 863.9 mm2, and < 881.1 mm2 at levels 0, 2, and 4 mm, respectively, should be described as having a “thin” alveolar morphotype. In these patients, extraction treatment, associated with a decrease in the alveolus area, should be exercised with caution

Intra and interspecific variability of the cephalic labial glands' secretions in male bumblebees: the case of Bombus (Thoracobombus) ruderarius (Müller) and B. (Thoracobombus) sylvarum (L.) [Hymenoptera, Apidae]

peer reviewedAccording to the species recognition concept of Paterson, the analyses of the secretions of the cephalic parts of the male labial glands confirm the conspecificity of Bombus (Thoracobombus) ruderarius ruderarius and B. (T.) r. montanus populations from the Pyrenees. These secretions were compared in B. ruderarius and B. sylvarum. We identified the same 7 major compounds as previously known for these species. We also identified 69 minor compounds. These minor compounds emphasise the close relationship between both species. Principal Component Analyses (PCA) were carried out on standardised peak areas of GC-MS chromatograms. The first PCA component is discriminant and shows no overlap between both species. Their secretions differ mostly by the relative concentration of their compounds rather than by their qualitative composition. On the contrary, PCA is unable to separate montanus from ruderarius. The larger variance in the secretions of B. ruderarius results from the very low concentration of the main compound (9-hexadecenol) in some specimens

The effects of six-day SSRI administration on diurnal cortisol secretion in healthy volunteers

RATIONALE: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been widely reported in depression, and evidence suggests that selective serotonin reuptake inhibitors (SSRIs) might exert their therapeutic effects through altering cortisol secretion. OBJECTIVE: This study assessed the effects of SSRI administration on diurnal cortisol secretion in healthy volunteers. METHODS: Sixty-four healthy men and women were randomised to receive either 10 mg escitalopram or placebo for six days in a double-blind fashion. On day six of medication, saliva samples were obtained at home for measurement of diurnal cortisol parameters (cortisol slope, cortisol awakening response, total daily cortisol output). RESULTS: Women receiving escitalopram had significantly steeper cortisol slopes across the day compared with those receiving placebo (F(1, 36) = 7.54, p = 0.009). This alteration in cortisol slope was driven by increases in waking cortisol levels (F(1, 35) = 9.21, p = 0.005). Escitalopram did not have any significant effect on the cortisol awakening response or the total daily cortisol output. CONCLUSIONS: Flattened cortisol slopes have been seen in depression. The results of this study suggest that escitalopram might exert its therapeutic effect in women in part through correction of a flattened diurnal cortisol rhythm

The biological effects of bilirubin photoisomers

Although phototherapy was introduced as early as 1950's, the potential biological effects of bilirubin photoisomers (PI) generated during phototherapy remain unclear. The aim of our study was to isolate bilirubin PI in their pure forms and to assess their biological effects in vitro. The three major bilirubin PI (ZE- and EZ-bilirubin and Z-lumirubin) were prepared by photo-irradiation of unconjugated bilirubin. The individual photoproducts were chromatographically separated (TLC, HPLC), and their identities verified by mass spectrometry. The role of Z-lumirubin (the principle bilirubin PI) on the dissociation of bilirubin from albumin was tested by several methods: peroxidase, fluorescence quenching, and circular dichroism. The biological effects of major bilirubin PI (cell viability, expression of selected genes, cell cycle progression) were tested on the SH-SY5Y human neuroblastoma cell line. Lumirubin was found to have a binding site on human serum albumin, in the subdomain IB (or at a close distance to it); and thus, different from that of bilirubin. Its binding constant to albumin was much lower when compared with bilirubin, and lumirubin did not affect the level of unbound bilirubin (Bf). Compared to unconjugated bilirubin, bilirubin PI did not have any effect on either SH-SY5Y cell viability, the expression of genes involved in bilirubin metabolism or cell cycle progression, nor in modulation of the cell cycle phase. The principle bilirubin PI do not interfere with bilirubin albumin binding, and do not exert any toxic effect on human neuroblastoma cells

Pheromone analysis of the bumble bee subgenus Sibiricobombus Vogt suggests Bombus niveatus Kriechbaumer and Bombus vorticosus Gerstaecker are conspecific (Hymenoptera, Apidae, Bombus)

peer reviewedThree taxa of the subgenus Sibiricobombus live in the Near-East mountain steppes: Bombus niveatus, B. sulfureus and B. vorticosus. The latter is also present in the Balkan. B. niveatus and B. vorticosus can only be distinguished based on color pattern. B. sulfureus differs in coat color and in genitalia. We identified 40 compounds in the secretions of the labial glands of these taxa, among which 7 were detected for the first time in labial cephalic gland secretions of bumblebee males. Whereas the secretions of the male cephalic labial glands of B. sulfureus are very different from those of B. niveatus and B. vorticosus, we found no significant difference between the latter. We conclude that B. sulfureus is a valid species, whereas B. vorticosus is a mere subspecies of B. niveatus: Bombus niveatus ssp. vorticosus Gerstaecker nov. status

Chiral Metafilms and Surface Enhanced Raman Scattering For Enantiomeric Discrimination of Helicoid Nanoparticles

Chiral nanophotonic platforms provide a means of creating near fields with both enhanced asymmetric properties and intensities. They can be exploited for optical measurements that allow enantiomeric discrimination at detection levels greater than 6 orders of magnitude than is achieved with conventional chirally sensitive spectroscopic methods based on circularly polarized light. The optimal approach for exploiting nanophotonic platforms for chiral detection would be to use spectroscopic methods that provide a local probe of changes in the near field environment induced by the presence of chiral species. Here we show that surface enhanced Raman spectroscopy (SERS) is such a local probe of the near field environment. We have used it to achieve enantiomeric discrimination of chiral helicoid nanoparticles deposited on left and right-handed enantiomorphs of a chiral metafilm. Hotter electromagnetic hotspots are created for matched combinations of helicoid and metafilms (left-left and right-right), while mismatched combinations leads to significantly cooler electromagnetic hotspots. This large enantiomeric dependency on hotspot intensity is readily detected using SERS with the aid of an achiral Raman reporter molecule. In effect we have used SERS to distinguish between the different EM environments of the plasmonic diastereomers produced by mixing chiral nanoparticles and metafilms. The work demonstrates that by combining chiral nanophotonic platforms with established SERS strategies new avenues in ultrasensitive chiral detection can be opened

Towards an improvement of optically stimulated luminescence (OSL) age uncertainties: modelling OSL ages with systematic errors, stratigraphic constraints and radiocarbon ages using the R package BayLum

Statistical analysis has become increasingly important in optically stimulated luminescence (OSL) dating since it has become possible to measure signals at the single-grain scale. The accuracy of large chronological datasets can benefit from the inclusion, in chronological modelling, of stratigraphic constraints and shared systematic errors. Recently, a number of Bayesian models have been developed for OSL age calculation; the R package “BayLum” presented herein allows different models of this type to be implemented, particularly for samples in stratigraphic order which share systematic errors. We first show how to introduce stratigraphic constraints in BayLum; then, we focus on the construction, based on measurement uncertainties, of dose covariance matrices to account for systematic errors specific to OSL dating. The nature (systematic versus random) of errors affecting OSL ages is discussed, based – as an example – on the dose rate determination procedure at the IRAMAT-CRP2A laboratory (Bordeaux). The effects of the stratigraphic constraints and dose covariance matrices are illustrated on example datasets. In particular, the benefit of combining the modelling of systematic errors with independent ages, unaffected by these errors, is demonstrated. Finally, we discuss other common ways of estimating dose rates and how they may be taken into account in the covariance matrix by other potential users and laboratories. Test datasets are provided as a Supplement to the reader, together with an R markdown tutorial allowing the reproduction of all calculations and figures presented in this study.</p

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Genomic reconstruction of the SARS-CoV-2 epidemic in England.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021