Proton pump inhibitors induced fungal dysbiosis in patients with gastroesophageal reflux disease

Gut mycobiota inhabits human gastrointestinal lumen and plays a role in human health and disease. We investigated the influence of proton pump inhibitors (PPIs) on gastric mucosal and fecal mycobiota in patients with gastroesophageal reflux diseases (GERD) by using Internal Transcribed Spacer 1 sequencing. A total of 65 participants were included, consisting of the healthy control (HC) group, GERD patients who did not use PPIs (nt-GERD), and GERD patients who used PPIs, which were further divided into short-term (s-PPI) and long-term PPI user (l-PPI) groups based on the duration of PPI use. The alpha diversity and beta diversity of gastric mucosal mycobiota in GERD patients with PPI use were significantly different from HCs, but there were no differences between s-PPI and l-PPI groups. LEfSe analysis identified Candida at the genus level as a biomarker for the s-PPI group when compared to the nt-GERD group. Meanwhile, Candida, Nothojafnea, Rhizodermea, Ambispora, and Saccharicola were more abundant in the l-PPI group than in the nt-GERD group. Furthermore, colonization of Candida in gastric mucosa was significantly increased after PPI treatment. However, there was no significant difference in Candida colonization between patients with endoscopic esophageal mucosal breaks and those without. There were significant differences in the fecal mycobiota composition between HCs and GERD patients regardless whether or not they used PPI. As compared to nt-GERD patient samples, there was a high abundance of Alternaria, Aspergillus, Mycenella, Exserohilum, and Clitopilus in the s-PPI group. In addition, there was a significantly higher abundance of Alternaria, Aspergillus, Podospora, Phallus, and Monographella in the l-PPI group than nt-GERD patients. In conclusion, our study indicates that dysbiosis of mycobiota was presented in GERD patients in both gastric mucosal and fecal mycobiota. PPI treatment may increase the colonization of Candida in the gastric mucosa in GERD patients

Study on stress performance and free brickwork height limit of traditional chinese cavity wall

Tradicionalni kineski zid sa šupljinom često je izložen in-plane i out-of-plane oštećenjima tijekom prirodnih nepogoda poput oluja i zemljotresa. Međutim, otpor potresu i vjetru zida sa šupljinom, zatvorene konstrukcije, rijetko se proučava. Umjesto toga, sprječavanje najgorega i napori za stvaranje sigurnosti koncentrirani su na konstrukcijsku analizu i štete od potresa glavne konstrukcije. Usmjerivši se na tehnike zidanja kod 2 uobičajena tipa zida sa šupljinom i 1 vrste punog zida, u ovom se radu konstruira specijalni uređaj za opterećenje i koristi za ispitivanje in-plane i out-of-plane naprezanja zida sa šupljinom i punog zida pod horizontalnim opterećenjem. Rezultati pokazuju da su sva out-of-plane oštećenja rezultat nedovoljne izdržljivosti na savijanje; zid sa šupljinom ima daleko nižu out-of-plane nosivost nego puni zid. Uz to, postoje znatna ograničenja visine kod zidanja zida sa šupljinom zbog potresa i snažnih vjetrova, s obzirom na shematski dijagram interne sile konzolnog nosača i na osnovu izmjerene savojno-vlačne i smične čvrstoće. Ustanovljeno je da out-of-plane ponašanje određuje granice zidanja opekom. Autori predlažu da se na svakom katu postave vezne konstrukcije ako zid sa šupljinom treba biti povezan s glavnom konstrukcijom.Traditional Chinese cavity wall often suffers in-plane and out-of-plane damages in natural disasters like gales and earthquakes. However, the seismic and wind resistance of the cavity wall, an enclosure structure, are seldom studied in the engineering field. Instead, the disaster prevention and relief efforts are concentrated on the structural analysis and seismic damage of the main structure. Focusing on the bricklaying methods for 2 common types of cavity walls and 1 kind of solid wall, this paper designs a special loading device and uses it to examine the in-plane and out-of-plane stress performance of cavity wall and solid wall under the horizontal load. The results show that all out-of-plane damages have resulted from the flexural-bending failure of the bend; the cavity wall has far lower out-of-plane bearing capacity than the solid wall. Moreover, the free brickwork height limits of the cavity wall under the action of earthquake and wind load are deducted respectively, in reference to the schematic diagram of the internal force of the cantilever beam and on the basis of the measured flexural-tensile strength and shear strength. It is found that the out-of-plane performance controls the brickwork limits. The authors suggest that connecting structures should be installed on each floor if the cavity wall is to be connected with the main structure

Adsorption equilibrium, isotherm, kinetics, and thermodynamic of modified bentonite for removing Rhodamine B

116-125Anionic and cationic surfactant modified sodium bentonite (Na-Bt) has been prepared by the cationic surfactant cetyltrimethyl ammonium bromide (CTAB) and the anionic surfactant sodium dodecyl benzene sulfonate (SDBS) to sodium bentonite, respectively. The properties of the modified samples are characterized by XRD, SEM, BET and FT-IR. The results of characterization shown that the cationic surfactant had changed the structure and properties of natural sodium bentonite, which proved that surfactants had been successfully implanted into sodium bentonite. But anionic surfactant had no change, this manifested SDBS didn’t insert the layers of bentonite. In addition, adsorption experiments of Rhodamine B (RhB) proved that the modified sodium bentonite adsorption performance is greatly improved. The adsorption experiments also indicated that CTAB-bentonite had the largest adsorption capacity compared with SDBS-bentonite due to the formation of a highly effective partition medium by cationic surfactant micelle. The adsorption data of RhB is analyzed with the isothermal model, thermodynamics and kinetics. Overall, this study provided high-efficiency method for the removal RhB by the surfactant modified bentonite

Allogeneic Mesenchymal Stem Cell Therapy for Bisphosphonate-Related Jaw Osteonecrosis in Swine

Bisphosphonates (BPs), which are used to treat a variety of clinical disorders, have the side effect of jawbone necrosis. Currently, there is no reliable treatment for BP-related osteonecrosis of the jaw (BRONJ) due to a lack of understanding of its pathogenesis. To investigate the pathogenesis of BRONJ and observe the treatment effect of bone marrow mesenchymal stem cell (BMMSC) transplantation, we established a preclinical animal model of BRONJ in miniature pigs (minipigs). After treatment with zoledronic acid, the clinical and radiographic manifestations of BRONJ could be observed in minipigs after first premolar extraction. The biological and immunological properties of BMMSCs were impaired in the BP-treated minipigs. Moreover, the ratio of Foxp3-positive regulatory T-cells (Tregs) in peripheral blood decreased, and interleukin (IL)-17 increased in the serum of BP-treated minipigs. After allogeneic BMMSC transplantation via intravenous infusion, mucosal healing and bone reconstruction were observed; IL-17 levels were reduced; and Tregs were elevated. In summary, we established a clinically relevant BRONJ model in minipigs and tested a promising allogeneic BMMSC-based therapy, which may have potential clinical applications for treating BRONJ. © Copyright 2013, Mary Ann Liebert, Inc. 2013

The Effect of Fecal Microbiota Transplantation on a Child with Tourette Syndrome

Tourette syndrome is a neuropsychiatric disorder with onset in childhood. New therapies are needed to effectively manage and treat this condition. Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis. Here, we report a case in which fecal microbiota transplantation (FMT) is used to treat a child with Tourette syndrome, whose symptoms ameliorated dramatically in the following eight weeks

Cell-based Immunotherapy with Mesenchymal Stem Cells Cures Bisphosphonate-related Osteonecrosis of the Jaw-like Disease in Mice

Patients on high-dose bisphosphonate and immunosuppressive therapy have an increased risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ); despite the disease severity, its pathophysiology remains unknown, and appropriate therapy is not established. Here we have developed a mouse model of BRONJ-like disease that recapitulates major clinical and radiographic manifestations of the human disease, including characteristic features of an open alveolar socket, exposed necrotic bone or sequestra, increased inflammatory infiltrates, osseous sclerosis, and radiopaque alveolar bone. We show that administration of zoledronate, a potent aminobisphosphonate, and dexamethasone, an immunosuppressant drug, causes BRONJ-like disease in mice in part by suppressing the adaptive regulatory T cells, Tregs, and activating the inflammatory T-helper-producing interleukin 17 cells, Th17. Most interestingly, we demonstrate that systemic infusion with mesenchymal stem cells (MSCs) prevents and cures BRONJ-like disease possibly via induction of peripheral tolerance, shown as an inhibition of Th17 and increase in Treg cells. The suppressed Tregs/Th17 ratio in zoledronate- and dexamethasone-treated mice is restored in mice undergoing salvage therapy with Tregs. These findings provide evidence of an immunity-based mechanism of BRONJ-like disease and support the rationale for in vivo immunomodulatory therapy using Tregs or MSCs to treat BRONJ. © 2010 American Society for Bone and Mineral Research

Pituitary tumor transforming gene-1 haplotypes and risk of pituitary adenoma: a case-control study

<p>Abstract</p> <p>Background</p> <p>It has been suggested that pituitary adenoma results from accumulation of multiple genetic and/or epigenetic aberrations, which may be identified through association studies. As pituitary tumor transforming gene-1 (<it>PTTG1</it>)/securin plays a critical role in promoting genomic instability in pituitary neoplasia, the present study explored the association of <it>PTTG1 </it>haplotypes with the risk of pituitary adenoma.</p> <p>Methods</p> <p>We genotyped five <it>PTTG1 </it>haplotype-tagging SNPs (htSNP) by PCR-RFLP assays in a case-control study, which included 280 Han Chinese patients diagnosed with pituitary adenoma and 280 age-, gender- and geographically matched Han Chinese controls. Haplotypes were reconstructed according to the genotyping data and linkage disequilibrium status of the htSNPs.</p> <p>Results</p> <p>No significant differences in allele and genotype frequencies of the htSNPs were observed between pituitary adenoma patients and controls, indicating that none of the individual <it>PTTG1 </it>SNPs examined in this study is associated with the risk of pituitary adenoma. In addition, no significant association was detected between the reconstructed <it>PTTG1 </it>haplotypes and pituitary adenoma cases or the controls.</p> <p>Conclusions</p> <p>Though no significant association was found between <it>PTTG1 </it>haplotypes and the risk of pituitary adenoma, this is the first report on the association of individual <it>PTTG1 </it>SNPs or <it>PTTG1 </it>haplotypes with the risk of pituitary adenoma based on a solid study; it will provide an important reference for future studies on the association between genetic alterations in <it>PTTG1 </it>and the risk of pituitary adenoma or other tumors.</p

Human Remains from the Pleistocene-Holocene Transition of Southwest China Suggest a Complex Evolutionary History for East Asians

BACKGROUND: Later Pleistocene human evolution in East Asia remains poorly understood owing to a scarcity of well described, reliably classified and accurately dated fossils. Southwest China has been identified from genetic research as a hotspot of human diversity, containing ancient mtDNA and Y-DNA lineages, and has yielded a number of human remains thought to derive from Pleistocene deposits. We have prepared, reconstructed, described and dated a new partial skull from a consolidated sediment block collected in 1979 from the site of Longlin Cave (Guangxi Province). We also undertook new excavations at Maludong (Yunnan Province) to clarify the stratigraphy and dating of a large sample of mostly undescribed human remains from the site. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a detailed comparison of cranial, including a virtual endocast for the Maludong calotte, mandibular and dental remains from these two localities. Both samples probably derive from the same population, exhibiting an unusual mixture of modern human traits, characters probably plesiomorphic for later Homo, and some unusual features. We dated charcoal with AMS radiocarbon dating and speleothem with the Uranium-series technique and the results show both samples to be from the Pleistocene-Holocene transition: ∼14.3-11.5 ka. CONCLUSIONS/SIGNIFICANCE: Our analysis suggests two plausible explanations for the morphology sampled at Longlin Cave and Maludong. First, it may represent a late-surviving archaic population, perhaps paralleling the situation seen in North Africa as indicated by remains from Dar-es-Soltane and Temara, and maybe also in southern China at Zhirendong. Alternatively, East Asia may have been colonised during multiple waves during the Pleistocene, with the Longlin-Maludong morphology possibly reflecting deep population substructure in Africa prior to modern humans dispersing into Eurasia