Diabetic Ketoacidosis Induces Tau Hyperphosphorylation in Rat Brain.

Background: Diabetes mellitus (DM) increases the risk for cognitive impairment and Alzheimer's disease (AD). Diabetic ketoacidosis (DKA), a serious complication of DM, may also cause brain damage and further AD, but the underlying molecular mechanisms remain unclear. Objective: Our objective was to understand how DKA can promote neurodegeneration in AD. Methods: We induced DKA in rats through intraperitoneal injection of streptozotocin, followed by starvation for 48 hours and investigated AD-related brain alterations focusing on tau phosphorylation. Results: We found that DKA induced hyperphosphorylation of tau protein at multiple sites associated with AD. Studies of tau kinases and phosphatases suggest that the DKA-induced hyperphosphorylation of tau was mainly mediated through activation of c-Jun N-terminal kinase and downregulation of protein phosphatase 2A. Disruption of the mTOR-AKT (the mechanistic target of rapamycin-protein kinase B) signaling pathway and increased levels of synaptic proteins were also observed in the brains of rats with DKA. Conclusions: These results shed some light on the mechanisms by which DKA may increase the risk for AD.

Resistance phenotype and genetic features of a heterogeneous vancomycin intermediate-resistant Staphylococcus aureus strain from an immunocompromised patient.

Strain C1 was successfully isolated from an immunosuppressed patient with persistent bacteremia, who had not previously been exposed to glycopeptide antibiotics. This strain was found to be a heterogeneous vancomycin intermediate-resistant Staphylococcus aureus (hVISA). It is noteworthy that, following a brief period of vancomycin treatment, strains C6, C8, and C9, which were obtained from blood and other body parts, exhibited a significant reduction in heterogeneity as determined by population analysis profile-area under the curve (PAP-AUC) detection. Genotyping analysis revealed that these bacterial strains belonged to the same SCCmecIVa-ST59-t437-agrI genotype and shared the same virulome and resistome. In this study, a comparative genomics analysis was conducted between strain C1 and strain N315 to identify potential hVISA-associated mutations. Ultimately, a total of 205 mutation sites in 19 candidate genes, likely associated with the hVISA phenotype, were identified.

An early juvenile of Kunpengopterus sinensis (Pterosauria) from the Late Jurassic in China.

The Wukongopteridae is a transitional clade between the long- and short-tailed pterosaur groups, and at least ten specimens have been studied without a determined juvenile specimen. Here, we described a small-sized Kunpengopterus sinensis, less than half the size of the holotype, which is the smallest specimen in wukongopterids. Based on unossified small elements, unfused cranial and postcranial elements, and grooves on the bone surface, this specimen is thought to be at least an early juvenile or even a late hatchling. By comparing the juvenile and subadult specimens of K. sinensis, we have found that the mid region of the upper and lower jaws had a higher growth rate than the anterior part, and that the growth rates were similar in most postcranial elements except for a higher rate in the caudal vertebrae. We revised the previous diagnosis of K. sinensis and specified that two characteristics, nasoantorbital fenestra approximately 40% of the skull length and a thin and relatively short maxillary process of the jugal, should be diagnostic in subadult or adult specimens. We have also found that pedal features are stable during ontogeny and can be diagnostic in juvenile, subadult or adult specimens in K. sinensis.

Clinical significance of sirtuin 1 level in sepsis: correlation with disease risk, severity, and mortality risk

This study aimed to investigate the value of sirtuin 1 (SIRT1) in differentiating sepsis patients from healthy controls (HCs), and its correlation with inflammation, disease severity, as well as prognosis in sepsis patients. Serum samples were collected from 180 sepsis patients and 180 age- and gender-matched HCs. The SIRT1 level in the serum samples was detected by enzyme-linked immunoassay. The clinical data of the sepsis patients were documented, and their disease severity scores and 28-day mortality rate were assessed. SIRT1 was decreased in sepsis patients compared with HCs, and the receiver operating characteristic curve (ROC) showed that SIRT1 distinguished sepsis patients from HCs (area under the curve (AUC): 0.901; 95% confidence interval (CI): 0.868-0.934). In sepsis patients, SIRT1 negatively correlated with serum creatinine (Scr), white blood cells (WBC), C-reactive protein (CRP), acute physiology, and chronic health evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score, while it positively correlated with albumin. No correlation of SIRT1 with primary infection site or primary organism was observed. Furthermore, SIRT1 was reduced in 28-day non-survivors compared with 28-day survivors, and subsequent ROC showed that SIRT1 predicted 28-day mortality of sepsis patients (AUC: 0.725; 95% CI: 0.651-0.800), and its prognostic value was not inferior to Scr, albumin, WBC, and CRP, but was less than SOFA score and APACHE II score. In conclusion, measurement of serum SIRT1 might assist with the optimization of disease assessment, management strategies, and survival surveillance in sepsis patients.

Clinical significance of sirtuin 1 level in sepsis: correlation with disease risk, severity, and mortality risk.

This study aimed to investigate the value of sirtuin 1 (SIRT1) in differentiating sepsis patients from healthy controls (HCs), and its correlation with inflammation, disease severity, as well as prognosis in sepsis patients. Serum samples were collected from 180 sepsis patients and 180 age- and gender-matched HCs. The SIRT1 level in the serum samples was detected by enzyme-linked immunoassay. The clinical data of the sepsis patients were documented, and their disease severity scores and 28-day mortality rate were assessed. SIRT1 was decreased in sepsis patients compared with HCs, and the receiver operating characteristic curve (ROC) showed that SIRT1 distinguished sepsis patients from HCs (area under the curve (AUC): 0.901; 95% confidence interval (CI): 0.868-0.934). In sepsis patients, SIRT1 negatively correlated with serum creatinine (Scr), white blood cells (WBC), C-reactive protein (CRP), acute physiology, and chronic health evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score, while it positively correlated with albumin. No correlation of SIRT1 with primary infection site or primary organism was observed. Furthermore, SIRT1 was reduced in 28-day non-survivors compared with 28-day survivors, and subsequent ROC showed that SIRT1 predicted 28-day mortality of sepsis patients (AUC: 0.725; 95% CI: 0.651-0.800), and its prognostic value was not inferior to Scr, albumin, WBC, and CRP, but was less than SOFA score and APACHE II score. In conclusion, measurement of serum SIRT1 might assist with the optimization of disease assessment, management strategies, and survival surveillance in sepsis patients.

Author Correction: The first theropod dinosaur (Coelurosauria, Theropoda) from the base of the Romualdo Formation (Albian), Araripe Basin, Northeast Brazil.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The first theropod dinosaur (Coelurosauria, Theropoda) from the base of the Romualdo Formation (Albian), Araripe Basin, Northeast Brazil.

The Romualdo Formation (Araripe Basin) is worldwide known for the large number of well-preserved fossils but the dinosaur record is rather scarce. Here we describe a new coelurosaur, which is the first tetrapod recovered from the basal layers of this stratigraphic unit that consist of dark shales. Aratasaurus museunacionali gen. et sp. nov. is known by an incomplete but articulated right hind limb with the distal portion of the femur, proximal half of tibia and incomplete pes. The new species differs from other coelurosaurs by a medial fossa in the tibia and digits II, III and IV being symmetric. The phylogenetic analysis recovered Aratasaurus museunacionali closely related to Zuolong salleei, forming a basal coelurosaur lineage. The paleohistology indicate that the specimen is a juvenile, with an estimated body length around 3.12 m. The new taxon represents the first occurrence of basal coelurosaurians in the Araripe Basin and suggests a widespread distribution of this group during the Lower Cretaceous.

New Material of Sinopterus (Pterosauria, Tapejaridae) from the Early Cretaceous Jehol Biota of China.

Tapejaridae is a clade of toothless pterosaurs typically characterized by a large nasoantorbital fenestra and a premaxillary crest that extends from the anterior to the posterior part of the skull. Sinopterus dongi was the first reported Chinese tapejarid. Another genus "Huaxiapterus" was described, but it was later on determined that "Huaxiapterus" is in fact an invalid name. Here, we report on a new juvenile specimen of Sinopterus atavismus from the Jiufotang Formation of western Liaoning, China, and revise the diagnosis of this species. Sinopterus atavismus does not present a square-like crest. Moreover the feature that groove in the ventral part of the second or third phalanx of manual digit IV is not diagnostic of the species. In the new material, the skull preserves a pointed process in the middle part of the dorsal margin of the premaxillary crest, which is different from other Chinese tapejarids. Considering the new specimen is known from a large skeleton that differed from the holotype, this difference may be related to ontogeny, as the premaxillary crest of the holotype is short and does not extend as long as that of the new specimen.

A new saurolophine hadrosaurid (Dinosauria: Ornithopoda) from the Upper Cretaceous of Shandong, China.

A new saurolophine hadrosaurid, Laiyangosaurus youngi gen. et sp. nov. is described and phylogenetically analyzed based on several cranial elements from the Jingangkou Formation, Wangshi Group, Upper Cretaceous of Laiyang, Shandong, China. Laiyangosaurus youngi differs from other members of the saurolophine clade on the basis of a number of autapomorphies, including a prominent and narrow ridge on the lateral side of the nasal which forms the posterodorsal and posterior margin of the circumnasal depression, a primary ridge that runs along most of the maxillary tooth row that is slightly deflected posteriorly, a retroarticular process of the surangular that is dorsolateroposteriorlly recurved, and orbital margins that are wider than the infratemporal margins of the jugal. This new taxon can be further distinguished by a number of unique combination of characters, including dorsal margin of nasal is flat, absence supracranial crest, a relatively shallow and rostrodorsally directed caudal margin of the lacrimal process of the jugal, and one or more foramina present on the rostral surface of the premaxilla. A phylogenetic analysis indicates that L. youngi comprises a monophyletic clade, which is known as Edmontosaurini.

Association of Severity of Coronary Lesions with Bone Mineral Density in Postmenopausal Women.

BACKGROUND: Coronary artery disease (CAD) and osteoporosis (OP) are common diseases in postmenopausal women. In both cross-sectional and longitudinal epidemiologic studies, low bone mass has been related to increased frequency of CAD. However, available data on the relationship between bone mineral density (BMD) and severity of coronary lesions is limited. OBJECTIVE: To investigate association between the BMD and severity of coronary lesions assessed by Gensini score in postmenopausal women. METHODS: This study included 122 postmenopausal women who were diagnosed with CAD. These patients were divided into two groups according to the severity of coronary lesions assessed by the Gensini score - patients with mild coronary lesions (Gensini score < 25) and patients with severe coronary lesions (Gensini score ≥ 25). Femoral neck mineral density was measured with dual energy X-ray absorptiometry (DXA). RESULTS: The study included postmenopausal women aged 64.31 ± 4.71 years, 85 of whom (69.7%) exhibited severe coronary lesions. Participants with severe coronary lesions had a significantly higher T score than did those with mild coronary lesions at the femoral neck (p < 0.05). The mean T-score was -0.84 ± 1.01 in mild coronary lesions group, -1.42 ± 1.39 in severe coronary lesions group (p < 0.05). Multivariable logistic regression analysis showed that osteopenia-osteoporosis at the Femoral neck (odds ratio 2.73; 95% confidence interval 1.06 to 6.13) was associated with an increased risk of developing severe coronary lesions. The multiple regression model showed that T-scores (b = -0.407, SE = 0.151, p=0.007) were the independent predictors of Gensini score. CONCLUSION: The relationship between severity of coronary lesions and BMD was significant in postmenopausal women. BMD, a low-cost technique involving minimal radiation exposure, widely used for osteoporosis screening, is a promising marker of severity of coronary lesions.

Association of Severity of Coronary Lesions with Bone Mineral Density in Postmenopausal Women / Associação entre Gravidade das Lesões Coronarianas e Densidade Mineral Óssea em Mulheres Pós-Menopausa

Abstract Background: Coronary artery disease (CAD) and osteoporosis (OP) are common diseases in postmenopausal women. In both cross-sectional and longitudinal epidemiologic studies, low bone mass has been related to increased frequency of CAD. However, available data on the relationship between bone mineral density (BMD) and severity of coronary lesions is limited. Objective: To investigate association between the BMD and severity of coronary lesions assessed by Gensini score in postmenopausal women. Methods: This study included 122 postmenopausal women who were diagnosed with CAD. These patients were divided into two groups according to the severity of coronary lesions assessed by the Gensini score - patients with mild coronary lesions (Gensini score < 25) and patients with severe coronary lesions (Gensini score ≥ 25). Femoral neck mineral density was measured with dual energy X-ray absorptiometry (DXA). Results: The study included postmenopausal women aged 64.31 ± 4.71 years, 85 of whom (69.7%) exhibited severe coronary lesions. Participants with severe coronary lesions had a significantly higher T score than did those with mild coronary lesions at the femoral neck (p < 0.05). The mean T-score was −0.84 ± 1.01 in mild coronary lesions group, −1.42 ± 1.39 in severe coronary lesions group (p < 0.05). Multivariable logistic regression analysis showed that osteopenia-osteoporosis at the Femoral neck (odds ratio 2.73; 95% confidence interval 1.06 to 6.13) was associated with an increased risk of developing severe coronary lesions. The multiple regression model showed that T-scores (b = −0.407, SE = 0.151, p=0.007) were the independent predictors of Gensini score. Conclusion: The relationship between severity of coronary lesions and BMD was significant in postmenopausal women. BMD, a low-cost technique involving minimal radiation exposure, widely used for osteoporosis screening, is a promising marker of severity of coronary lesions.

Resumo Fundamento: A doença arterial coronariana (DAC) e a osteoporose são doenças comuns em mulheres pós-menopausa. Tanto em estudos transversais como em estudos epidemiológicos longitudinais, a massa óssea diminuída foi relacionada à frequência aumentada de DAC. No entanto, dados disponíveis sobre a relação entre densidade mineral óssea (DMO) e gravidade das lesões coronarianas são limitados. Objetivo: Investigar a associação entre DMO e gravidade das lesões coronarianas avaliadas pelo escore de Gensini em mulheres pós-menopausa. Métodos: Este estudo incluiu 122 mulheres pós-menopausa diagnosticadas com DAC. As pacientes foram divididas em dois grupos de acordo com a gravidade das lesões coronarianas avaliada pelo escore de Gensini - pacientes com lesões coronarianas leves (escore de Gensini < 25) e pacientes com lesões coronarianas graves (escore de Gensini ≥ 25). A densidade mineral do colo femoral foi medida por absorção de raios-X de dupla energia (DXA). Resultados: O estudo incluiu mulheres pós-menopausa com idade de 64,31 ± 4,71 anos, 85 delas (69,7%) com lesões coronarianas graves. Pacientes com lesões coronarianas graves apresentaram um escore T mais elevado que aquelas com lesões coronarianas leves no colo femoral (p < 0,05). O escore T médio foi -0,84 ± 1,01 no grupo com lesões leves, e -1,42 ± 1,39 no grupo com lesões graves (p < 0,05). A análise de regressão logística multivariada mostrou que a osteopenia-osteoporose no colo femoral (odds ratio 2,73; intervalo de confiança de 95% 1,06 - 6,13) esteve associada com um risco aumentado de se desenvolver lesões coronarianas graves. O modelo de regressão múltipla mostrou que os escores T (b = -0,407; EP= 0,151; p = 0,007) foram preditores independentes do escore de Gensini. Conclusão: Encontrou-se uma relação significativa entre a gravidade das lesões coronarianas e a DMO em mulheres pós-menopausa. DMO, uma técnica de baixo custo que envolve mínima exposição à radiação, e amplamente utilizada no rastreamento de osteoporose, é um marcador promissor da gravidade de lesões coronarianas graves.

Premaxillary crest variation within the Wukongopteridae (Reptilia, Pterosauria) and comments on cranial structures in pterosaurs

ABSTRACT Cranial crests show considerable variation within the Pterosauria, a group of flying reptiles that developed powered flight. This includes the Wukongopteridae, a clade of non-pterodactyloids, where the presence or absence of such head structures, allied with variation in the pelvic canal, have been regarded as evidence for sexual dimorphism. Here we discuss the cranial crest variation within wukongopterids and briefly report on a new specimen (IVPP V 17957). We also show that there is no significant variation in the anatomy of the pelvis of crested and crestless specimens. We further revisit the discussion regarding the function of cranial structures in pterosaurs and argue that they cannot be dismissed a priori as a valuable tool for species recognition.

Premaxillary crest variation within the Wukongopteridae (Reptilia, Pterosauria) and comments on cranial structures in pterosaurs.

Cranial crests show considerable variation within the Pterosauria, a group of flying reptiles that developed powered flight. This includes the Wukongopteridae, a clade of non-pterodactyloids, where the presence or absence of such head structures, allied with variation in the pelvic canal, have been regarded as evidence for sexual dimorphism. Here we discuss the cranial crest variation within wukongopterids and briefly report on a new specimen (IVPP V 17957). We also show that there is no significant variation in the anatomy of the pelvis of crested and crestless specimens. We further revisit the discussion regarding the function of cranial structures in pterosaurs and argue that they cannot be dismissed a priori as a valuable tool for species recognition.

Eggshell and Histology Provide Insight on the Life History of a Pterosaur with Two Functional Ovaries.

The counterpart of a previously described non-pterodactyloid pterosaur with an egg revealed the presence of a second egg inside the body cavity of this gravid female. It clearly shows that pterosaurs had two functional oviducts and demonstrates that the reduction of one oviduct was not a prerequisite for developing powered flight, at least in this group. Compositional analysis of one egg suggests the lack of a hard external layer of calcium carbonate. Histological sections of one femur lack medullary bone and further demonstrate that this pterosaur reached reproductive maturity before skeletal maturity. This study shows that pterosaurs laid eggs even smaller than previously thought and had a reproductive strategy more similar to basal reptiles than to birds. Whether pterosaurs were highly precocial or needed parental care is still open to debate.

New toothed flying reptile from Asia: close similarities between early Cretaceous pterosaur faunas from China and Brazil.

Despite the great increase in pterosaur diversity in the last decades, particularly due to discoveries made in western Liaoning (China), very little is known regarding pterosaur biogeography. Here, we present the description of a new pterosaur from the Jiufotang Formation that adds significantly to our knowledge of pterosaur distribution and enhances the diversity of cranial anatomy found in those volant creatures. Guidraco venator gen. et sp. nov. has an unusual upward-directed frontal crest and large rostral teeth, some of which surpass the margins of the skull and lower jaw when occluded. The new species is closely related to a rare taxon from the Brazilian Crato Formation, posing an interesting paleobiogeographic problem and supporting the hypothesis that at least some early Cretaceous pterosaur clades, such as the Tapejaridae and the Anhangueridae, might have originated in Asia. The association of the new specimen with coprolites and the cranial morphology suggest that G. venator preyed on fish.

New long-tailed pterosaurs (Wukongopteridae) from western Liaoning, China.

Two almost complete long-tailed pterosaurs from the Linglongta, Jianchang County, western Liaoning, China, are described and represent new taxa referred to the non-pterodactyloid clade Wukongopteridae. Kunpengopterus sinensis gen. et sp. nov. differs from other members of this clade mainly by the rounded posterior region of the skull, thick lacrimal process of the jugal and lack of a bony premaxillary crest. This species further shows a soft tissue crest above the frontal, a comparatively larger wing finger, and the proximal segment of the second pedal phalanx of the fifth toe shorter than in other wukongopterids. The second new species is referred to the genus Darwinopterus, D. linglongtaensis sp. nov. based on the posterior region of the skull. It further differs from other wukongopterid pterosaurs by the thin lacrimal process of the jugal, foramen on nasal process rounded, and by having the second pedal phalanx of the fifth toe less curved (115°). Several differences among the Wukongopteridae can be found in the dentition and the feet, suggesting that they might have occupied slightly different ecological niches. The long-tailed Changchengopterus pani is tentatively referred to this clade and new diagnosis for the wukongopterids Wukongopterus lii and Darwinopterus modularis is provided.

New long-tailed pterosaurs (Wukongopteridae) from western Liaoning, China

Two almost complete long-tailed pterosaurs from the Linglongta, Jianchang County, western Liaoning, China, are described and represent new taxa referred to the non-pterodactyloid clade Wukongopteridae. Kunpengopterus sinensis gen. et sp. nov. differs from other members of this clade mainly by the rounded posterior region of the skull, thick lacrimal process of the jugal and lack of a bony premaxillary crest. This species further shows a soft tissue crest above the frontal, a comparatively larger wing finger, and the proximal segment of the second pedal phalanx of the fifth toe shorter than in other wukongopterids. The second new species is referred to the genus Darwinopterus, D. linglongtaensis sp. nov. based on the posterior region of the skull. It further differs from other wukongopterid pterosaurs by the thin lacrimal process of the jugal, foramen on nasal process rounded, and by having the second pedal phalanx of the fifth toe less curved (115°). Several differences among the Wukongopteridae can be found in the dentition and the feet, suggesting that they might have occupied slightly different ecological niches. The long-tailed Changchengopterus pani is tentatively referred to this clade and new diagnosis for the wukongopterids Wukongopterus lii and Darwinopterus modularis is provided.

Dois novos pterossauros de cauda longa procedentes de Linglongta, Jianchang County da região oeste de Liaoning, China, são descritos e referidos ao clado Wukongopteridae. Kunpengopterus sinensis gen. et sp. nov. difere dos demais integrantes desse clado basicamente pela região mais arredondada da parte posterior do crânio, pelo espesso processo lacrimal do jugal e pela ausência de uma crista óssea premaxilar. Esta espécie apresenta uma crista formada por tecido mole acima da região frontal e possui o dedo alar proporcionalmente maior do que nos demais wukongopterídeos. A segunda espécie é referida ao gênero Darwinopterus, D. linglongtaensis sp. nov., com base na região posterior do crânio. Difere dos deais pterossauros wukongopterídeos por possuir o processo lacrimal do jugal delgado, o forâmen no processo nasal arredondado e pela condição menos curvada da segunda falange do quinto dígito do pé. As principais diferenças entre os Wukongopteridae são encontradas na dentição e nos pés, o que sugere que estes ocupavam nichos ecológicos ligeiramente distintos. O pterossauro de cauda longa Changchen-gopterus pani também é tentativamente referido a esse clado. Novas diagnoses para os wukongopterídeos Wukongopterus lii e Darwinopterus modularis são apresentadas.