ResearchPad - digestive-physiology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Longitudinal analysis of cost and dental utilization patterns for older adults in outpatient and long-term care settings in Minnesota]]> https://www.researchpad.co/article/elastic_article_14553 Dental utilization patterns and costs of providing comprehensive oral healthcare for older adults in different settings have not been examined.MethodsRetrospective longitudinal cohort data from Apple Tree Dental (ATD) were analyzed (N = 1,159 total; 503 outpatients, 656 long-term care residents) to describe oral health status at presentation, service utilization patterns, and care costs. Generalized estimating equation (GEE) repeated measures analysis identified significant contributors to service cost over the three-year study period.ResultsCohort mean age was 74 years (range = 55–104); the outpatient (OP) group was younger compared to the long-term care (LTC) group. Half (56%) had Medicaid, 22% had other insurance, and 22% self-paid. Most (72%) had functional dentitions (20+ teeth), 15% had impaired dentitions (9–19 teeth), 6% had severe tooth loss (1–8 teeth), and 7% were edentulous (OP = 2%, LTC = 11%). More in the OP group had functional dentition (83% vs. 63% LTC). The number of appointments declined from 5.0 in Year 1 (OP = 5.7, LTC = 4.4) to 3.3 in Year 3 (OP = 3.6, LTC = 3.0). The average cost to provide dental services was $1,375/year for three years (OP = $1,427, LTC = $1,336), and costs declined each year, from an average of $1,959 (OP = $2,068, LTC = $1,876) in Year 1 to $1,016 (OP = $989, LTC = $1,037) by Year 3. Those with functional dentition at presentation were significantly less costly than those with 1–19 teeth, while edentulous patients demonstrated the lowest cost and utilization. Year in treatment, insurance type, dentition type, and problem-focused first exam were significantly associated with year-over-year cost change in both OP and LTC patients.ConclusionCosts for providing comprehensive dental care in OP and LTC settings were similar, modest, and declined over time. Dentate patients with functional dentition and edentulous patients were less costly to treat. LTC patients had lower utilization than OP patients. Care patterns shifted over time to increased preventive care and decreased restorative care visits. ]]> <![CDATA[Anatomy of the dinosaur Pampadromaeus barberenai (Saurischia—Sauropodomorpha) from the Late Triassic Santa Maria Formation of southern Brazil]]> https://www.researchpad.co/article/5c76fe1bd5eed0c484e5b4e9

Sauropodomorphs are the most abundant and diverse clade of Triassic dinosaurs, but the taxonomy of their earliest (Carnian) representatives is still poorly understood. One such taxon is Pampadromaeus barberenai, represented by a nearly complete disarticulated skeleton recovered from the upper part of the Santa Maria Formation of Rio Grande do Sul, Brazil. Here, the osteology of Pam. barberenai is fully described for the first time. Detailed comparisons with other Carnian sauropodomorphs reveal a unique anatomy, corroborating its status as a valid species. Potential autapomorphies of Pam. barberenai can be seen in the articulation of the sacral zygapophyses, the length of the pectoral epipodium, the shape of the distal articulation of the femur and the proximal articulation of metatarsal 1. A novel phylogenetic study shows that relationships among the Carnian sauropodomorphs are poorly constrained, possibly because they belong to a “zone of variability”, where homoplasy abounds. Yet, there is some evidence that Pam. barberenai may nest within Saturnaliidae, along with Saturnalia tupiniquim and Chromogisaurus novasi, which represents the sister group to the larger sauropodomorphs, i.e. Bagualosauria.

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<![CDATA[Comparisons of Schansitherium tafeli with Samotherium boissieri (Giraffidae, Mammalia) from the Late Miocene of Gansu Province, China]]> https://www.researchpad.co/article/5c6c7573d5eed0c4843cfdbf

We are describing and figuring for the first time skulls of Schansitherium tafeli, which are abundant in the Gansu area of China from the Late Miocene. They were animals about the size of Samotherium with shorter necks that had two pairs of ossicones that merge at the base, which is unlike Samotherium. The anterior ossicones consist of anterior lineations, which may represent growth lines. They were likely mixed feeders similar to Samotherium. Schansitherium is tentatively placed in a very close position to Samotherium. Samotherium and Schansitherium represent a pair of morphologically very similar species that likely coexisted similarly to pairs of modern species, where the main difference is in the ossicones. Pairs of ruminants in Africa, for example, exist today that differ mostly in their horn shape but otherwise are similar in size, shape, and diet. The absence of Schansitherium from Europe is interesting, however, as Samotherium is found in both locations. While is it challenging to interpret neck length and ossicone shape in terms of function in combat, we offer our hypothesis as to how the two species differed in their fighting techniques.

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<![CDATA[Dissecting the pathways coordinating patterning and growth by plant boundary domains]]> https://www.researchpad.co/article/5c536af0d5eed0c484a47c21

Boundary domains play important roles during morphogenesis in plants and animals, but how they contribute to patterning and growth coordination in plants is not understood. The CUC genes determine the boundary domains in the aerial part of the plants and, in particular, they have a conserved role in regulating leaf complexity across Angiosperms. Here, we used tooth formation at the Arabidopsis leaf margin controlled by the CUC2 transcription factor to untangle intertwined events during boundary-controlled morphogenesis in plants. Combining conditional restoration of CUC2 function with morphometrics as well as quantification of gene expression and hormone signaling, we first established that tooth morphogenesis involves a patterning phase and a growth phase. These phases can be separated, as patterning requires CUC2 while growth can occur independently of CUC2. Next, we show that CUC2 acts as a trigger to promote growth through the activation of three functional relays. In particular, we show that KLUH acts downstream of CUC2 to modulate auxin response and that expressing KLUH can compensate for deficient CUC2 expression during tooth growth. Together, we reveal a genetic and molecular network that allows coordination of patterning and growth by CUC2-defined boundaries during morphogenesis at the leaf margin.

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<![CDATA[Incidence of deformities and variation in shape of mentum and wing of Chironomus columbiensis (Diptera, Chironomidae) as tools to assess aquatic contamination]]> https://www.researchpad.co/article/5c40f776d5eed0c4843861ef

Constantly, aquatic ecosystems are under pressure by complex mixtures of contaminants whose effects are not always easy to evaluate. Due to this, organisms are sought in which early warning signs may be detected upon the presence of potentially toxic xenobiotic substances. Thereby, the study evaluated the incidence of deformities and other morphometric variations in the mentum and wing of Chironomus columbiensis exposed to water from some of the Colombian Andes affected by mining, agriculture, and cattle raising. Populations of C. columbiensis were subjected throughout their life cycle (24 days) for two generations (F1 and F2). Five treatments were carried out in controlled laboratory conditions (water from the site without impact, site of mining mercury, mining mercury + cyanide, cattle raising, and agriculture) and the respective control (reconstituted water). Thereafter, the percentage of deformities in the mentum was calculated, and for the morphometric analysis 29 landmarks were digitized for the mentum and 12 for the wing. As a result, four types of deformities were registered in the C. columbiensis mentum, like absence of teeth, increased number of teeth, fusion and space between teeth, none of them detected in the individuals from the control. Additionally, the highest incidence of deformity in F1 occurred in the treatment of mining mercury, while for F2 this took place in the treatments of mining mercury + cyanide, cattle raising and agriculture. Differences were also found with respect to the morphometric variations of the mentum and wing of C. columbiensis among the control and the treatments with water from the creeks intervened. The treatments of mining mercury + cyanide and agriculture had the highest morphological variation in the mentum and wing of C. columbiensis. The results suggest that the anthropogenic impacts evaluated generate alterations in the oral apparatus of the larval state of C. columbiensis and in the adult state provoke alterations in the wing shape (increased width and reduced basal area). These deformities may be related to multiple stress factors, among them the xenobiotics metabolized by the organisms under conditions of environmental contamination.

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<![CDATA[Oral health status of the disabled compared with that of the non-disabled in Korea: A propensity score matching analysis]]> https://www.researchpad.co/article/5c46658fd5eed0c484519c96

Background

There are many types of disabilities, and each type has a variety related to socioeconomic factors. Such factors affect to many health problems of the disabled. However, surveys of the oral health status of the disabled in Korea are rare.

Objective

The purpose of this study was to estimate oral health disparity through comparing oral health status of the disabled to the non-disabled, adjusted for the net effect of the disability on oral health status.

Methods

A cross-sectional study was conducted among the disabled in urban and suburban areas in Korea from June to September 2016. People with physical, mental, and multiple disabilities took part in this survey. The clinical examinations were carried out by trained dentists. Statistical analysis was performed to quantify the association between oral health and socioeconomic status after restricting the analysis using a propensity score matching method.

Results

The disabled had more DMFT, DT, and MT, fewer FT, and fewer teeth than the non-disabled based on entire groups (P<0.01). No difference in the ratio of periodontitis was observed. The subjects with mental disabilities (MD) scored 3.09 (95% CI, 1.07–8.97), and those with multiple disabilities scored 4.37 (95% CI, 1.16–16.37) for edentulous status. The MD had an odds ratio of 1.34 (95% CI, 1.03–1.74), and those with multiple disabilities had an odds ratio of 1.75 (95% CI, 1.11–2.76) for the DMFT index.

Conclusions

These results represent poor oral health status of the disabled compared to the non-disabled. Consequentially, we can verify that not only the existence of disability but also the type of disability has a decisive effect on oral health condition. This comparison is necessary to widen our approach to evaluate the actual status condition of the disabled.

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<![CDATA[Stomach contents of the archaeocete Basilosaurus isis: Apex predator in oceans of the late Eocene]]> https://www.researchpad.co/article/5c3fa556d5eed0c484ca331a

Apex predators live at the top of an ecological pyramid, preying on animals in the pyramid below and normally immune from predation themselves. Apex predators are often, but not always, the largest animals of their kind. The living killer whale Orcinus orca is an apex predator in modern world oceans. Here we focus on an earlier apex predator, the late Eocene archaeocete Basilosaurus isis from Wadi Al Hitan in Egypt, and show from stomach contents that it fed on smaller whales (juvenile Dorudon atrox) and large fishes (Pycnodus mokattamensis). Our observations, the first direct evidence of diet in Basilosaurus isis, confirm a predator-prey relationship of the two most frequently found fossil whales in Wadi Al-Hitan, B. isis and D. atrox. This extends our understanding of their paleoecology. Late Eocene Basilosaurus isis, late Miocene Livyatan melvillei, and modern Orcinus orca are three marine apex predators known from relatively short intervals of time. Little is known about whales as apex predators through much of the Cenozoic era, and whales as apex predators deserve more attention than they have received.

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<![CDATA[Lost before found: A new species of whaler shark Carcharhinus obsolerus from the Western Central Pacific known only from historic records]]> https://www.researchpad.co/article/5c3667ccd5eed0c4841a6492

Carcharhinus obsolerus is described based on three specimens from Borneo, Thailand and Vietnam in the Western Central Pacific. It belongs to the porosus subgroup which is characterised by having the second dorsal-fin insertion opposite the anal-fin midbase. It most closely resembles C. borneensis but differs in tooth morphology and counts and a number of morphological characters, including lack of enlarged hyomandibular pores which are diagnostic of C. borneensis. The historic range of C. obsolerus sp. nov. is under intense fishing pressure and this species has not been recorded anywhere in over 80 years. There is an urgent need to assess its extinction risk status for the IUCN Red List of Threatened Species. With so few known records, there is a possibility that Carcharhinus obsolerus sp. nov. has been lost from the marine environment before any understanding could be gained of its full historic distribution, biology, ecosystem role, and importance in local fisheries.

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<![CDATA[Perinatal death and exposure to dental amalgam fillings during pregnancy in the population-based MoBa cohort]]> https://www.researchpad.co/article/5c141ed9d5eed0c484d2886a

Objectives

The aim was to gain knowledge regarding the risk of perinatal death related to exposure to dental amalgam fillings in the mother.

Design

Population-based observational cohort study.

Setting

The Norwegian Mother and Child Cohort Study, a Norwegian birth cohort of children born in 1999–2008 conducted by the Norwegian Institute of Public Health.

Participants

72,038 pregnant women with data on the number of teeth filled with dental amalgam.

Main outcome measures

Data on perinatal death (stillbirth ≥ 22 weeks plus early neonatal death 0–7 days after birth) were obtained from the Medical Birth Registry of Norway.

Results

The absolute risk of perinatal death ranged from 0.20% in women with no amalgam-filled teeth to 0.67% in women with 13 or more teeth filled with amalgam. Analyses including the number of teeth filled with amalgam as a continuous variable indicated an increased risk of perinatal death by increasing number of teeth filled with dental amalgam (crude OR 1.065, 95% CI 1.034 to 1.098, p<0.001). After adjustment for potential confounders (mothers' age, education, body mass index, parity, smoking during pregnancy, alcohol consumption during pregnancy) included as categorical variables, there was still an increased risk for perinatal death associated with increasing number of teeth filled with amalgam (ORadj 1.041, 95% CI 1.008 to 1.076, p = 0.015). By an increased exposure from 0 to 16 teeth filled with amalgam, the model predicted an almost doubled odds ratio (ORadj 1.915, 95% CI 1.12 to 3.28). In groups with 1 to 12 teeth filled with amalgam the adjusted odds ratios were slightly, but not significantly, increased. The group with the highest exposure (participants with 13 or more teeth filled with amalgam) had an adjusted OR of 2.34 (95% CI 1.27 to 4.32; p = 0.007).

Conclusion

The current findings suggest that the risk of perinatal death could increase in a dose-dependent way based on the mother’s number of teeth filled with dental amalgam. However, we cannot exclude that the relatively modest odds ratios could be a result of residual confounding. Additional studies on the relationship between exposure to dental amalgam fillings during pregnancy and perinatal death are warranted.

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<![CDATA[Microleakage of conventional light-cure resin-based fissure sealant and resin-modified glass ionomer sealant after application of a fluoride varnish on demineralized enamel]]> https://www.researchpad.co/article/5c1966d3d5eed0c484b53005

Background

International guidelines on the prevention of caries recommend sealing of the pits and fissures of the permanent molars. There is no evidence on which type of material is most effective on demineralized enamel.

Aim

To evaluate the microleakage of a conventional light-cured, resin-based fissure sealant (LCRBS), GrandiO Seal, and a resin-modified glass ionomer sealant (RMGIS), Vitremer, after application of a fluoride varnish, Bifluorid 12, on demineralized enamel.

Design

80 human third molars were divided into eight groups. The groups combined the three study factors (1) type of enamel (intact or demineralized); (2) enamel non-varnished or varnished with Biflourid12; and (3) type of sealant (GrandiO Seal or Vitremer). The percentage of microleakage after thermocycling was measured using imaging analysis software. The Kruskal-Wallis plus Dunn tests were used to compare differences in microleakage in the different groups.

Results

The lowest microleakage was in the unvarnished groups, and was the same for GrandiO Seal and Vitremer. When varnish was applied, microleakage was greater in demineralized enamel than in intact enamel for both LCRBS and RMGIS.

Conclusion

The application of fluoride varnish on demineralized enamel increases the microleakage of both GrandiO Seal and Vitremer.

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<![CDATA[Patient-reported outcomes associated with different restorative techniques in pediatric dentistry: A systematic review and MTC meta-analysis]]> https://www.researchpad.co/article/5c12cf17d5eed0c484913ecb

Background

Despite the increasing number of studies evaluating patient reported outcome measures (PROs), there is no clearness regarding which restorative treatment offers major benefits based on the pediatric patient perspective.

Aim

To compare different restorative techniques in pediatric dentistry regarding patient-reported outcomes.

Design

Literature searching was carried out on prospective studies indexed in PubMed, Scopus and OpenGrey. A Mixed Treatment Comparisons (MTC) meta-analysis was undertaken considering the results from reviewed studies. Anxiety, pain and quality of life were extracted as mean with standard deviation, percentage of pain, and mean difference of scores with standard deviation, respectively. For direct comparisons, data were combined using a random-effect model. Heterogeneity was assessed with the I2 statistic. For indirect comparisons, fixed and random effects were chosen through comparison of competing models based on the Deviance Information Criteria (DIC). The expected efficacy ranking based on the posterior probabilities of all treatment rankings was also calculated.

Results

An initial search resulted in 4,322 articles, of which 17 were finally selected. Due to unavailability of data, only pain, anxiety and oral health related quality of life (OHRQoL) were statistically analyzed. The difference in means (95% CI) of anxiety between treatments using only hand instruments with or without chemomechanical agents were -5.35 (-6.42 to -4.20) and -5.79 (-7.77 to -3.79) respectively when compared to conventional treatment using rotary instruments and/or local anesthesia. Regarding pain, there was a trend for treatments without rotary instruments and local anesthesia to be less frequently reported as painful. No statistical difference was found intragroup nor among treatments for OHRQoL.

Conclusions

Anxiety and pain are directly related with more invasive restorative treatments. On the other hand, quality of life is not improved regardless of the restorative technique used. Further well-designed prospective studies regarding PROs in children are still necessary.

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<![CDATA[Cranial anatomy of the gorgonopsian Cynariops robustus based on CT-reconstruction]]> https://www.researchpad.co/article/5c084219d5eed0c484fcbc21

Gorgonopsia is one of the major clades of non-mammalian synapsids, and includes an array of large-bodied carnivores that were the top terrestrial predators of the late Permian. Most research on the clade has focused on these largest members; small-bodied gorgonopsians are relatively little-studied. Here, we redescribe a small gorgonopsian skull (MB.R.999) from the late Permian (Tropidostoma Assemblage Zone) of South Africa on the basis of neutron and synchrotron CT reconstructions, which yield new data on internal cranial morphology in Gorgonopsia. Because of the largely undistorted nature of MB.R.999, we were also able to reconstruct unossified areas such as the brain endocast and the otic labyrinth. MB.R.999 can be referred to the taxon Cynariops robustus based on its general skull proportions, postcanine tooth count, preparietal morphology, and vomerine morphology. We refer additional small gorgonopsian specimens from the Victoria West area to Cynariops robustus, and consider Cynarioides grimbeeki and Cynarioides laticeps to be synonymous with C. robustus. Inclusion of Cynariops in a phylogenetic analysis of Gorgonopsia recovers it within a large clade of African taxa, more closely related to Lycaenops and rubidgeines than Eriphostoma or Gorgonops.

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<![CDATA[The osteology of Periptychus carinidens: A robust, ungulate-like placental mammal (Mammalia: Periptychidae) from the Paleocene of North America]]> https://www.researchpad.co/article/5b60175a463d7e3bf2e777d5

Periptychus is the archetypal genus of Periptychidae, a clade of prolific Paleocene ‘condylarth’ mammals from North America that were among the first placental mammals to radiate after the end-Cretaceous extinction, remarkable for their distinctive dental anatomy. A comprehensive understanding of the anatomy of Periptychus has been hindered by a lack of cranial and postcranial material and only cursory description of existing material. We comprehensively describe the cranial, dental and postcranial anatomy of Periptychus carinidens based on new fossil material from the early Paleocene (Torrejonian) of New Mexico, USA. The cranial anatomy of Periptychus is broadly concurrent with the inferred plesiomorphic eutherian condition, albeit more robust in overall construction. The rostrum is moderately elongate with no constriction, the facial region is broad, and the braincase is small with a well-exposed mastoid on the posterolateral corner and tall sagittal and nuchal crests. The dentition of Periptychus is characterized by strongly crenulated enamel, enlarged upper and lower premolars with a tall centralised paracone/protoconid. The postcranial skeleton of Periptychus is that of a robust, medium-sized (~20 Kg) stout-limbed animal that was incipiently mediportal and adopted a plantigrade stance. The structure of the fore- and hindlimb of Periptychus corresponds to that of a typically terrestrial mammal, while morphological features of the forelimb such as the low tubercles of the humerus, long and prominent deltopectoral crest, pronounced medial epicondyle, and hemispherical capitulum indicate some scansorial and/or fossorial ability. Most striking is the strongly dorsoplantarly compressed astragalus of Periptychus, which in combination with the distal crus and calcaneal morphology indicates a moderately mobile cruropedal joint. The anatomy of Periptychus is unique and lacks any extant analogue; it combines a basic early placental body plan with numerous unique specializations in its dental, cranial and postcranial anatomy that exemplify the ability of mammals to adapt and evolve following catastrophic environmental upheaval.

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<![CDATA[On the design of power gear trains: Insight regarding number of stages and their respective ratios]]> https://www.researchpad.co/article/5c032df9d5eed0c4844f8a6a

This paper presents a formulation for selecting the stage ratios and number of stages in a multistage transmission with a given desired total transmission ratio in a manner that maximizes efficiency, maximizes acceleration, or minimizes the mass of the transmission. The formulation is used to highlight several implications for gear train design, including the fact that minimizing rotational inertia and mass are competing objectives with respect to optimal selection of stage ratios, and that both rotational inertia and mass can often be minimized by increasing the total number of stages beyond a minimum realizable number. Additionally, a multistage transmission will generally provide maximum acceleration when the stage ratios increase monotonically from the motor to the load. The transmission will have minimum mass when the stage ratios decrease monotonically. The transmission will also provide maximum efficiency when the corresponding stages employ constant stage ratios. This paper aims to use this optimization formulation to elucidate tradeoffs between various common objectives in gear train design (efficiency, acceleration, and mass).

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<![CDATA[An Insight into the Transcriptome of the Digestive Tract of the Bloodsucking Bug, Rhodnius prolixus]]> https://www.researchpad.co/article/5989d9e8ab0ee8fa60b6c009

The bloodsucking hemipteran Rhodnius prolixus is a vector of Chagas' disease, which affects 7–8 million people today in Latin America. In contrast to other hematophagous insects, the triatomine gut is compartmentalized into three segments that perform different functions during blood digestion. Here we report analysis of transcriptomes for each of the segments using pyrosequencing technology. Comparison of transcript frequency in digestive libraries with a whole-body library was used to evaluate expression levels. All classes of digestive enzymes were highly expressed, with a predominance of cysteine and aspartic proteinases, the latter showing a significant expansion through gene duplication. Although no protein digestion is known to occur in the anterior midgut (AM), protease transcripts were found, suggesting secretion as pro-enzymes, being possibly activated in the posterior midgut (PM). As expected, genes related to cytoskeleton, protein synthesis apparatus, protein traffic, and secretion were abundantly transcribed. Despite the absence of a chitinous peritrophic membrane in hemipterans - which have instead a lipidic perimicrovillar membrane lining over midgut epithelia - several gut-specific peritrophin transcripts were found, suggesting that these proteins perform functions other than being a structural component of the peritrophic membrane. Among immunity-related transcripts, while lysozymes and lectins were the most highly expressed, several genes belonging to the Toll pathway - found at low levels in the gut of most insects - were identified, contrasting with a low abundance of transcripts from IMD and STAT pathways. Analysis of transcripts related to lipid metabolism indicates that lipids play multiple roles, being a major energy source, a substrate for perimicrovillar membrane formation, and a source for hydrocarbons possibly to produce the wax layer of the hindgut. Transcripts related to amino acid metabolism showed an unanticipated priority for degradation of tyrosine, phenylalanine, and tryptophan. Analysis of transcripts related to signaling pathways suggested a role for MAP kinases, GTPases, and LKBP1/AMP kinases related to control of cell shape and polarity, possibly in connection with regulation of cell survival, response of pathogens and nutrients. Together, our findings present a new view of the triatomine digestive apparatus and will help us understand trypanosome interaction and allow insights into hemipteran metabolic adaptations to a blood-based diet.

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<![CDATA[Cranial Anatomy and Palaeoneurology of the Archosaur Riojasuchus tenuisceps from the Los Colorados Formation, La Rioja, Argentina]]> https://www.researchpad.co/article/5989db3bab0ee8fa60bd4fa9

Riojasuchus tenuisceps Bonaparte 1967 is currently known from four specimens, including two complete skulls, collected in the late 1960s from the upper levels of the Los Colorados Formation (Late Triassic), La Rioja, Argentina. Computed tomography (CT) scans of the skulls of the holotype and a referred specimen of Riojasuchus tenuisceps and the repreparation of the latter allows recognition of new features for a detailed analysis of its cranial anatomy and its comparison with a wide variety of other archosauriform taxa. The diagnosis of Riojasuchus tenuisceps is emended and two autapomorphies are identified on the skull: (1) a deep antorbital fossa with its anterior and ventral edges almost coinciding with the same edges of the maxilla itself and (2) a suborbital fenestra equal in size to the palatine-pterygoid fenestra. Also, the first digital 3D reconstruction of the encephalon of Riojasuchus tenuisceps was carried out to study its neuroanatomy, showing a shape and cranial nerve disposition consistent to that of other pseudosuchians.

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<![CDATA[Increased Oral Detection, but Decreased Intestinal Signaling for Fats in Mice Lacking Gut Microbiota]]> https://www.researchpad.co/article/5989da6fab0ee8fa60b9426f

Germ-free (GF) mice lacking intestinal microbiota are significantly leaner than normal (NORM) control mice despite consuming more calories. The contribution of microbiota on the recognition and intake of fats is not known. Thus, we investigated the preference for, and acceptance of, fat emulsions in GF and NORM mice, and associated changes in lingual and intestinal fatty acid receptors, intestinal peptide content, and plasma levels of gut peptides. GF and NORM C57Bl/6J mice were given 48-h two-bottle access to water and increasing concentrations of intralipid emulsions. Gene expression of the lingual fatty acid translocase CD36 and protein expression of intestinal satiety peptides and fatty-acid receptors from isolated intestinal epithelial cells were determined. Differences in intestinal enteroendocrine cells along the length of the GI tract were quantified. Circulating plasma satiety peptides reflecting adiposity and biochemical parameters of fat metabolism were also examined. GF mice had an increased preference and intake of intralipid relative to NORM mice. This was associated with increased lingual CD36 (P<0.05) and decreased intestinal expression of fatty acid receptors GPR40 (P<0.0001), GPR41 (P<0.0001), GPR43 (P<0.05), and GPR120 (P<0.0001) and satiety peptides CCK (P<0.0001), PYY (P<0.001), and GLP-1 (P<0.001). GF mice had fewer enteroendocrine cells in the ileum (P<0.05), and more in the colon (P<0.05), relative to NORM controls. Finally, GF mice had lower levels of circulating leptin and ghrelin (P<0.001), and altered plasma lipid metabolic markers indicative of energy deficits. Increased preference and caloric intake from fats in GF mice are associated with increased oral receptors for fats coupled with broad and marked decreases in expression of intestinal satiety peptides and fatty-acid receptors.

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<![CDATA[Tuberous Sclerosis Complex-1 Deficiency Attenuates Diet-Induced Hepatic Lipid Accumulation]]> https://www.researchpad.co/article/5989daefab0ee8fa60bc0be3

Non-alcoholic fatty liver disease (NAFLD) is causally linked to type 2 diabetes, insulin resistance and dyslipidemia. In a normal liver, insulin suppresses gluconeogenesis and promotes lipogenesis. In type 2 diabetes, the liver exhibits selective insulin resistance by failing to inhibit hepatic glucose production while maintaining triglyceride synthesis. Evidence suggests that the insulin pathway bifurcates downstream of Akt to regulate these two processes. Specifically, mTORC1 has been implicated in lipogenesis, but its role on hepatic steatosis has not been examined. Here, we generated mice with hepatocyte-specific deletion of Tsc1 to study the effects of constitutive mTORC1 activation in the liver. These mice developed normally but displayed mild hepatomegaly and insulin resistance without obesity. Unexpectedly, the Tsc1-null livers showed minimal signs of steatosis even under high-fat diet condition. This ‘resistant’ phenotype was reversed by rapamycin and could be overcome by the expression of Myr-Akt. Moreover, rapamycin failed to reduce hepatic triglyceride levels in models of steatosis secondary to Pten ablation in hepatocytes or high-fat diet in wild-type mice. These observations suggest that mTORC1 is neither necessary nor sufficient for steatosis. Instead, Akt and mTORC1 have opposing effects on hepatic lipid accumulation such that mTORC1 protects against diet-induced steatosis. Specifically, mTORC1 activity induces a metabolic shift towards fat utilization and glucose production in the liver. These findings provide novel insights into the role of mTORC1 in hepatic lipid metabolism.

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<![CDATA[Modulation of Protein Fermentation Does Not Affect Fecal Water Toxicity: A Randomized Cross-Over Study in Healthy Subjects]]> https://www.researchpad.co/article/5989dab3ab0ee8fa60bac28a

Objective

Protein fermentation results in production of metabolites such as ammonia, amines and indolic, phenolic and sulfur-containing compounds. In vitro studies suggest that these metabolites might be toxic. However, human and animal studies do not consistently support these findings. We modified protein fermentation in healthy subjects to assess the effects on colonic metabolism and parameters of gut health, and to identify metabolites associated with toxicity.

Design

After a 2-week run-in period with normal protein intake (NP), 20 healthy subjects followed an isocaloric high protein (HP) and low protein (LP) diet for 2 weeks in a cross-over design. Protein fermentation was estimated from urinary p-cresol excretion. Fecal metabolite profiles were analyzed using GC-MS and compared using cluster analysis. DGGE was used to analyze microbiota composition. Fecal water genotoxicity and cytotoxicity were determined using the Comet assay and the WST-1-assay, respectively, and were related to the metabolite profiles.

Results

Dietary protein intake was significantly higher during the HP diet compared to the NP and LP diet. Urinary p-cresol excretion correlated positively with protein intake. Fecal water cytotoxicity correlated negatively with protein fermentation, while fecal water genotoxicity was not correlated with protein fermentation. Heptanal, 3-methyl-2-butanone, dimethyl disulfide and 2-propenyl ester of acetic acid are associated with genotoxicity and indole, 1-octanol, heptanal, 2,4-dithiapentane, allyl-isothiocyanate, 1-methyl-4-(1-methylethenyl)-benzene, propionic acid, octanoic acid, nonanoic acid and decanoic acid with cytotoxicity.

Conclusion

This study does not support a role of protein fermentation in gut toxicity. The identified metabolites can provide new insight into colonic health.

Trial Registration

ClinicalTrial.gov NCT01280513

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<![CDATA[Indocyanine Green Video Angiography Predicts Outcome of Extravasation Injuries]]> https://www.researchpad.co/article/5989db06ab0ee8fa60bc8480

Background

Extravasation of cytotoxic drugs is a serious complication of systemic cancer treatment. Still, a reliable method for early assessment of tissue damage and outcome prediction is missing. Here, we demonstrate that the evaluation of blood flow by indocyanine green (ICG) angiography in the extravasation area predicts for the need of surgical intervention.

Methods

Twenty-nine patients were evaluated by ICG angiography after extravasation of vesicant or highly irritant cytotoxic drugs administered by peripheral i.v. infusion. Tissue perfusion as assessed by this standardized method was correlated with clinical outcome.

Results

The perfusion index at the site of extravasation differed significantly between patients with reversible tissue damage and thus healing under conservative management (N = 22) versus those who needed surgical intervention due to the development of necrosis (N = 7; P = 0.0001). Furthermore, in patients benefiting from conservative management, the perfusion index was significantly higher in the central extravasation area denoting hyperemia, when compared with the peripheral area (P = 0.0001).

Conclusions

In this patient cohort, ICG angiography as indicator of local perfusion within the extravasation area was of prognostic value for tissue damage. ICG angiography could thus be used for the early identification of patients at risk for irreversible tissue damage after extravasation of cytotoxic drugs.

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