As shown in our previous study, inspiration after swallowing (SW-I) increases during the bi-level positive airway pressure ventilation (BiPAP) in healthy subjects because swallowing-associated ...non-inspiratory flow (SNIF) triggers inspiratory support, while SW-I during continuous positive pressure ventilation (CPAP) is rare. In the present study, we evaluated the coordination between breathing and swallowing during spontaneous breathing, BiPAP, and CPAP in patients with chronic obstructive pulmonary disease (COPD).
This study is a prospective intervention study at the Hoshigaoka Medical Center (November 01, 2015-April 30, 2018). We simultaneously recorded the respiratory flow, laryngeal motion, and swallowing sounds during saliva swallowing in patients with COPD. We estimated the respiratory phase after swallowing, frequency of SNIF, the duration of the respiratory pause during swallowing, and timing of swallowing in the respiratory cycle and compared these parameters among control, CPAP, and BiPAP conditions.
The expiration after swallowing (SW-E) frequency was associated with the occurrence of SNIF (
<0.01), pause duration ≤0.8 s (
<0.01), and timing of swallowing at the intermediate respiratory phase (50-80% of the respiratory cycle from the onset of inspiration) (
<0.01). In particular, the occurrence of SNIF most substantially affected the SW-E frequency. The SW-I frequencies under the control, CPAP, and BiPAP conditions were 35.0%, 3.0%, and 37.7%, respectively. The pause durations were shorter during CPAP and BiPAP than under the control condition (
<0.01). During CPAP, the occurrence rates of SW-E. Residual denotes the percentage difference between observed and expected values (residual =10.8:
<0.01) and SNIF (residual =9.1:
<0.01) were significantly increased, and timing of swallowing shifted toward the intermediate respiratory phase (residual=3.5:
<0.01).
CPAP decreases the SW-I frequency, increases the SNIF occurrence, and normalizes the timing of swallowing, all of which suggest that CPAP alleviates the risk of aspiration in patients with COPD.
Extremity reconstruction surgery is increasingly performed rather than amputation for patients with large-segment pathologic bone loss. Debate persists as to the optimal void filler for this "limb ...salvage" surgery, whether metal or allograft bone. Clinicians focus on optimizing important functional gains for patients, and the risk of devastating implant infection has been thought to be similar regardless of implant material. Recent insights into infection pathophysiology are challenging this equipoise, however, with both basic science data suggesting a novel mechanism of infection of Staphylococcus aureus (the most common infecting agent) into the host lacunar-canaliculi network, and also clinical data revealing a higher rate of infection of allograft over metal. The current translational study was therefore developed to bridge the gap between these insights in a longitudinal murine model of infection of allograft bone and metal. Real-time Staphylococci infection characteristics were quantified in cortical bone vs metal, and both microarchitecture of host implant and presence of host immune response were assessed. An orders-of-magnitude higher bacterial burden was established in cortical allograft bone over both metal and cancellous bone. The establishment of immune-evading microabscesses was confirmed in both cortical allograft haversian canal and the submicron canaliculi network in an additional model of mouse femur bone infection. These study results reveal a mechanism by which Staphylococci evasion of host immunity is possible, contributing to elevated risks of infection in cortical bone. The presence of this local infection reservoir imparts massive clinical implications that may alter the current paradigm of osteomyelitis and bulk allograft infection treatment.
Oceanic anoxic events were time intervals in the Mesozoic characterized by widespread distribution of marine organic matter-rich sediments (black shales) and significant perturbations in the global ...carbon cycle. These perturbations are globally recorded in sediments as carbon isotope excursions irrespective of lithology and depositional environment. During the early Toarcian, black shales were deposited on the epi- and pericontinental shelves of Pangaea, and these sedimentary rocks are associated with a pronounced (ca. 7 ‰) negative (organic) carbon isotope excursion (CIE) which is thought to be the result of a major perturbation in the global carbon cycle. For this reason, the lower Toarcian is thought to represent an oceanic anoxic event (the T-OAE). If the T-OAE was indeed a global event, an isotopic expression of this event should be found beyond the epi- and pericontinental Pangaean localities. To address this issue, the carbon isotope composition of organic matter (δ13Corg of lower Toarcian organic matter-rich cherts from Japan, deposited in the open Panthalassa Ocean, was analysed. The results show the presence of a major (>6 ‰) negative excursion in δ13Corg that, based on radiolarian biostratigraphy, is a correlative of the lower Toarcian negative CIE known from Pangaean epi- and pericontinental strata. A smaller negative excursion in δ13Corg (ca. 2 ‰) is recognized lower in the studied succession. This excursion may, within the current biostratigraphic resolution, represent the excursion recorded in European epicontinental successions close to the Pliensbachian/Toarcian boundary. These results from the open ocean realm suggest, in conjunction with other previously published datasets, that these Early Jurassic carbon cycle perturbations affected the active global reservoirs of the exchangeable carbon cycle (deep marine, shallow marine, atmospheric).
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
BACKGROUND:There is a new method of transportation that started in our community in late 2017— rideshare electric scooters (e-scooters). These scooters have proven immensely popular and can now be ...found in many cities around the world. Despite the pervasiveness of e-scooters, their associated injury patterns are poorly understood. The purpose of this study was to describe our department’s experience at the epicenter of the e-scooter phenomenon that is sweeping the globe and to characterize operative orthopaedic injuries that are related to e-scooter accidents.
METHODS:We performed a retrospective chart review of all of the operative orthopaedic cases and trauma consults at 2 trauma centers (a level-I center and a level-II center) between September 2017 and August 2019. We identified all operative injuries in which the cause of injury was an e-scooter accident. Data that included demographics, mechanism of injury, diagnosis, and treatment were collected.
RESULTS:Seventy-five operative injuries were identified in 73 patients during the study period. The mean patient age was 35.4 years (range, 14 to 74 years), and the median age was 32 years. There were 4 pediatric patients (14, 15, 15, and 17 years old). Thirty-two patients (43.8%) sustained upper-extremity injuries, and 42 patients (57.5%) sustained lower-extremity injuries; 1 of these patients had both upper and lower-extremity injuries. Nine patients (12.3%) had open fractures. There were 7 hip fractures in patients with an average age of 42.4 years (range, 28 to 68 years). Seventy-one (97.3%) of 73 patients were e-scooter riders, and 2 (2.7%) were pedestrians who were struck by e-scooter riders.
CONCLUSIONS:E-scooters can cause serious injury. Seventy-three patients required operative treatment in just the first 2 years of e-scooter use in our community. Operative injuries occurred throughout the skeletal system, and several were injuries that are typically associated with high-energy trauma. Although, as a rule, e-scooter use is limited to adults and banned in high pedestrian-traffic areas in our city, the inclusion of 4 underage riders and 2 pedestrians in our cohort suggests that these rules are not always followed. As e-scooters continue to increase in popularity, additional steps should be taken to regulate their use and protect riders and the public.
Summary
The low affinity neurotrophin receptor p75NTR is known to be expressed in the mitotically quiescent basal layer (BL) of the normal esophageal epithelium. The aim of the present study was to ...detect oncogenic changes in the p75NTR‐positive BL during esophageal squamous carcinogenesis. The normal epithelium (NE), low‐grade intraepithelial neoplasia (LGN), high‐grade intraepithelial neoplasia (HGN), and esophageal squamous carcinoma (SCC), in which invasion was limited to the muscularis mucosa, were obtained from surgically removed esophagi. The expression of p75NTR, the proliferation marker ki67, hTERT, p53, and p63 was examined immunohistochemically. The expression of p75NTR was detected in these tissues with average staining indexes (number of stained cells/100 nucleated cells; SI) of 1.00, 0.99, 0.81, and 0.73, respectively. The expression of ki67 in the BL significantly increased with the progression from LGN to HGN. The expression of hTERT and p53 significantly increased with the progression from NE to LGN, and then increased in a stepwise manner in HGN and SCC, with SI (hTERT/p53) of 0.10/0.11, 0.32/0.45, 0.50/0.72, and 0.65/0.61, respectively. The expression of p63 showed no significant difference among NE, LGN, HGN, and SCC, with SI of 0.82, 0.77, 0.85, and 0.87, respectively. A correlation was observed between the expression of ki67 and p53 (P = 0.005), while a negative correlation was found between p75NTR and hTERT (P = 0.01). Our results demonstrated that phenotypic changes from quiescent to active proliferation in the p75NTR‐positive BL occurred during the progression from LGN to HGN. The altered expression of hTERT and p53 in the BL was detected in LGN, which suggested that additional oncogenic events that disrupt mitotic regulation in the p75NTR‐positive quiescent BL may play a crucial role in malignant transformation. Further investigations using the isolation and tracing of p75NTR‐positive cells in precancerous epithelia may provide us with a better understanding of squamous carcinogenesis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Radiation-tolerant n+-in-p silicon sensors were developed for use in very high radiation environments. Novel n+-in-p silicon strip and pixel sensors and test structures were fabricated, tested and ...evaluated, in order to understand the designs implemented. The resistance between the n+ implants (interstrip resistance), the electric potential of the p-stop, and the punch-through-protection (PTP) onset voltage were measured before and as a function of fluence after irradiation. The technology computer-aided design (TCAD) simulations were used to understand the radiation damage and fluence dependence of the structures. The decrease in the interstrip resistance is a consequence of increased leakage current. The decrease in the electric potential of the p-stop results from a build-up of positive charge in the silicon–silicon oxide interface. The decrease and subsequent increase in the PTP onset voltages results from the interface charge build-up and an increase in acceptor states.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cyclosporin A, a cyclic undecapeptide, and FK506 are efficient immunosuppressive agents. They also attract attention as effective
P-glycoprotein modulators that inhibit P-glycoprotein from binding to ...anticancer drugs and overcome multidrug resistance.
Cyclosporin A itself interacts with a common binding site of P-glycoprotein to which Vinca alkaloids and verapamil bind. We
were interested to determine whether cyclosporin A and FK506 are substrates for P-glycoprotein to transport, and we studied
their transcellular transport. In LLC-PK1 cells, derived from porcine kidney proximal tubule and forming a highly polarized
epithelium, cyclosporin A was transported in a saturable manner. LLC-GA5-COL300, a transformant cell line derived by transfecting
LLC-PK1 with human MDR1 cDNA isolated from normal adrenal gland, expresses P-glycoprotein specifically on the apical surface
and shows a typical multidrug-resistant phenotype. LLC-GA5-COL300 cells showed increased transport of cyclosporin A from the
basal to the apical side. Kinetic analysis showed that this transport was a typical saturable transport with the calculated
apparent Michaelis constant (Kappm) and the maximum flux (Vmax) as 8.4 microM and 2.4 nmol/mg protein/h, respectively. LLC-GA5-COL300
also showed increased transport of FK506 from the basal to the apical side. These results indicate that P-glycoprotein transports
the immunosuppressive agents cyclosporin A and FK506.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The period homolog genes Per1, Per2 and Per3 are important components of the circadian clock system. In addition to their role in maintaining circadian rhythm, these genes have been linked to mood ...disorders, stress response and vulnerability to addiction and alcoholism. In this study, we combined high-resolution sequence analysis and quantitative trait locus (QTL) mapping of gene expression and behavioral traits to identify Per3 as a compelling candidate for the interaction between circadian rhythm, alcohol and stress response. In the BXD family of mouse strains, sequence variants in Per3 have marked effects on steady-state mRNA and protein levels. As a result, the transcript maps as a cis-acting expression QTL (eQTL). We found that an insertion/deletion (indel) variant in a putative stress response element in the promoter region of Per3 causes local control of transcript abundance. This indel results in differences in protein binding affinities between the two alleles through the Nrf2 transcriptional activator. Variation in Per3 is also associated with downstream differences in the expression of genes involved in circadian rhythm, alcohol, stress response and schizophrenia. We found that the Per3 locus is linked to stress/anxiety traits, and that the basal expression of Per3 is also correlated with several anxiety and addiction-related phenotypes. Treatment with alcohol results in increased expression of Per3 in the hippocampus, and this effect interacts with acute restraint stress. Our data provide strong evidence that variation in the Per3 transcript is causally associated with and also responsive to stress and alcohol.
An effective oxygen diffusion-coefficient in gas diffusion layer (GDL) is critical for improving the performance of polymer electrolyte fuel cell (PEFC). Effective oxygen diffusion-coefficient of GDL ...decreases with increasing water saturation, and it leads to a drop in performance. Therefore, we developed a measuring technique for effective oxygen diffusion-coefficient of water-containing GDL. Saturation was measured through a sample weight change in the drying process. Using this technique we elucidated the relationship between effective oxygen diffusion-coefficient and water saturation in GDL. As a result, it was verified that the amount of decrease in effective oxygen diffusion-coefficient with water saturation is based on GDL hydrophobicity.
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