Search

Determination of prognosis in the triage process after traumatic brain injury (TBI) is difficult to achieve. Current severity measures like the Trauma and injury severity score (TRISS) and revised trauma score (RTS) rely on additional information from the Glasgow Coma Scale (GCS) and the Injury Severity Score (ISS) which may be inaccurate or delayed, limiting their usefulness in the rapid triage setting. We hypothesized that machine learning based estimations of GCS and ISS obtained through modeling of continuous vital sign features could be used to rapidly derive an automated RTS and TRISS. We derived variables from electrocardiograms (ECG), photoplethysmography (PPG), and blood pressure using continuous data obtained in the first 15 min of admission to build machine learning models of GCS and ISS (ML-GCS and ML-ISS). We compared the TRISS and RTS using ML-ISS and ML-GCS and its value using the actual ISS and GCS in predicting in-hospital mortality. Models were tested in TBI with systemic injury (head abbreviated injury scale (AIS) ≥ 1), and isolated TBI (head AIS ≥ 1 and other AIS ≤ 1). The area under the receiver operating characteristic curve (AUROC) was used to evaluate model performance. A total of 21,077 cases (2009–2015) were in the training set. 6057 cases from 2016 to 2017 were used for testing, with 472 (7.8%) severe TBI (GCS 3–8), 223 (3.7%) moderate TBI (GCS 9–12), and 5913 (88.5%) mild TBI (GCS 13–15). In the TBI with systemic injury group, ML-TRISS had similar AUROC (0.963) to TRISS (0.965) in predicting mortality. ML-RTS had AUROC (0.823) and RTS had AUROC 0.928. In the isolated TBI group, ML-TRISS had AUROC 0.977, and TRISS had AUROC 0.983. ML-RTS had AUROC 0.790 and RTS had AUROC 0.957. Estimation of ISS and GCS from machine learning based modeling of vital sign features can be utilized to provide accurate assessments of the RTS and TRISS in a population of TBI patients. Automation of these scores could be utilized to enhance triage and resource allocation during the ultra-early phase of resuscitation. [ABSTRACT FROM AUTHOR]

A novel and efficient mesoporous nano-absorbent for U(VI) removal was developed through an environment-friendly route by inducing the biomimetic mineralization of hydroxyapatite (HAP) on the bioinspired surface of polydopamine-graphene oxide (PDA-GO). PDA-GO/HAP exhibited the greatly rapid and efficient U(VI) removal within 2 min, and much higher U(VI) adsorption capacity of 433.07 mg·g−1 than that of GO and PDA-GO. The enhanced adsorption capacity was mainly attributed to the synergistic effect of O–H, –C=N–, and PO43− functional groups and the incorporation of uranyl ions by the formation of a new phase (chernikovite, H2(UO2)2(PO4)2·8H2O). The adsorption process of U(VI) fitted well with pseudo-second-order kinetic and Langmuir isotherm model. Moreover, PDA-GO/HAP showed a high U(VI) adsorption capacity in a broad range of pH values and owned good thermal stability. PDA-GO/HAP with various excellent properties made it a greatly promising adsorbent for extracting uranium. Our work developed a good strategy for constructing fast and efficient uranium-adsorptive biomimetic materials. [ABSTRACT FROM AUTHOR]

Intrahepatic cholestasis of pregnancy (ICP) is a female pregnancy-specific disorder that is characterized by increased serum bile acid and adverse fetal outcomes. The aetiology and mechanism of ICP are poorly understood; thus, existing therapies have been largely empiric. Here we show that the gut microbiome differed significantly between individuals with ICP and healthy pregnant women, and that colonization with gut microbiome from ICP patients was sufficient to induce cholestasis in mice. The gut microbiomes of ICP patients were primarily characterized by Bacteroides fragilis (B. fragilis), and B. fragilis was able to promote ICP by inhibiting FXR signaling via its BSH activity to modulate bile acid metabolism. B. fragilis-mediated FXR signaling inhibition was responsible for excessive bile acid synthesis and interrupted hepatic bile excretion to ultimately promote the initiation of ICP. We propose that modulation of the gut microbiota-bile acid-FXR axis may be of value for ICP treatment. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease that sometimes develops during pregnancy and is characterized by increased serum bile acid levels. Here the authors report that the gut microbiome species B. fragilis is enriched in patients with ICP and promotes ICP development in mice via inhibition of signalling though the bile acid receptor FXR. [ABSTRACT FROM AUTHOR]

Secondary neurologic decline (ND) after traumatic brain injury (TBI) is independently associated with outcome, but robust predictors of ND are lacking. In this retrospective analysis of consecutive isolated TBI admissions to the R. Adams Cowley Shock Trauma Center between November 2015 and June 2018, we aimed to develop a triage decision support tool to quantify risk for early ND. Three machine learning models based on clinical, physiologic, or combined characteristics from the first hour of hospital resuscitation were created. Among 905 TBI cases, 165 (18%) experienced one or more ND events (130 clinical, 51 neurosurgical, and 54 radiographic) within 48 h of presentation. In the prediction of ND, the clinical plus physiologic data model performed similarly to the physiologic only model, with concordance indices of 0.85 (0.824–0.877) and 0.84 (0.812–0.868), respectively. Both outperformed the clinical only model, which had a concordance index of 0.72 (0.688–0.759). This preliminary work suggests that a data-driven approach utilizing physiologic and basic clinical data from the first hour of resuscitation after TBI has the potential to serve as a decision support tool for clinicians seeking to identify patients at high or low risk for ND. [ABSTRACT FROM AUTHOR]

Purpose: To review the resections of endolymphatic sac tumor (ELST) and describe our experience in the surgical management of ELST. Methods: Retrospective investigation of consecutive patients who underwent resection of ELSTs at our hospital between 1999 and 2019. The symptoms, diagnosis, surgical findings, and outcomes were analyzed to develop a tumor staging system and corresponding surgical strategy. Results: Retrospective review revealed the surgical treatment of 22 ELSTs. Based on intraoperative findings of tumor extent and size, ELSTs were classified into two types. Type-I (n = 6) referred to the small tumors that were locally confined with limited invasion of semicircular canals and dura; type-II (n = 16) referred to the large tumors that presented extensive erosion of at least one anatomic structure apart from the semicircular canals and the dura around endolymphatic sac. In this case series, Type-I ELST is amenable to resection through a transmastoidal approach, and subtotal petrosectomy is appropriate for the resection of type-II ELST. Sensorineural hearing loss (SNHL) is the most commonly preoperative symptom in both two types of cases. Five type-II ELSTs experienced recurrence and underwent reoperation, whereas all type-I ELSTs did not. Conclusion: ELST usually results in SNHL (95%) at the time of diagnosis. The surgical strategy and prognosis of ELST resections are different between type-I and type-II: type-I ELST is amenable to transmastoidal approach with the preservation of facial nerve, whereas type-II ELST increase the surgical difficulty and the risk of recurrence, and subtotal petrosectomy is the basic requirement for the resection of type-II ELST. [ABSTRACT FROM AUTHOR]

Purpose: Locally advanced nasopharyngeal carcinoma (LANC) often invades the parapharyngeal space and internal carotid artery. Are patients with LANC invading carotid artery are at risk of massive neck hemorrhage after radiotherapy? Methods: This retrospective study included 130 LANC patients with carotid artery invasion admitted to our hospital between January 2012 and September 2019. All patients were treated with induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) ± epidermal growth factor receptor (EGFR) inhibitor. Univariate and multivariate analysis of risk factors were conducted for the prognosis and the occurrence of massive neck hemorrhage of LANC patients with carotid artery invasion. Outcomes: The 5-year progression-free survival (PFS), distant metastasis-free survival (DMFS), local nodal recurrence-free survival (LNRFS), local recurrence-free survival (LRFS), nodal recurrence-free survival (NRFS) and overall survival (OS) of the 130 patients were 75.2%, 76.8%, 90.0%, 93.9%, 95.8% and 87.2%, respectively. The incidence of fatal bleeding after radiotherapy was 2.3% (3/130). The primary site of the three cases were all the pharyngeal recess, with more than 270° carotid artery invasion, suffering nasopharyngeal necrosis after radiotherapy (2 of which were diabetics and 1 received re-radiation after recurrence). Univariate analysis showed that clinical stage was negatively correlated with DMFS and PFS (P < 0.05). The induction chemotherapy TP regimen, platinum-based concurrent chemotherapy and EGFR inhibitors (Nituzumab/Cetuximab) significantly improved PFS and DMFS (P < 0.05). Patients with hemoglobin levels > 110 g/L had significantly inferior PFS, DMFS and OS than those with hemoglobin levels ≤ 110 g/L (P < 0.05). Multivariate analysis showed that the EGFR inhibitor was an independent risk factor for PFS and DMFS, while the lowest hemoglobin level was an independent risk factor for OS. Conclusions: In LANC patients whose carotid artery invasion was < 270°, induction chemotherapy (IC) followed by helical tomotherapy (HT) and concurrent chemoradiotherapy (CCRT) with EGFR (epidermal growth factor receptor) inhibitor had mild and tolerable side effects, better PFS and DMFS, with no massive hemorrhage. In patients whose primary tumor was pharyngeal recess with carotid artery invasion ≥ 270°, poorly controlled diabetes or re-radiotherapy led to a higher risk of massive hemorrhage after radiotherapy. [ABSTRACT FROM AUTHOR]

Nonalcoholic steatohepatitis (NASH) has been linked with the gut-liver axis. Here, we investigate the potential for repurposing disulfiram (DSF), a drug commonly used to treat chronic alcoholism, for NASH. Using a mouse model, we show that DSF ameliorates NASH in a gut microbiota-dependent manner. DSF modulates the gut microbiota and directly inhibits the growth of Clostridium. Administration of Clostridium abolishes the ameliorating effects of DSF on NASH. Mechanistically, DSF reduces Clostridium-mediated 7α-dehydroxylation activity to suppress secondary bile acid biosynthesis, which in turn activates hepatic farnesoid X receptor signaling to ameliorate NASH. To assess the effect of DSF on human gut microbiota, we performed a self-controlled clinical trial (ChiCTR2100048035), including 23 healthy volunteers who received 250 mg-qd DSF for 7 days. The primary objective outcomes were to assess the effects of the intervention on the diversity, composition and functional profile of gut microbiota. The pilot study shows that DSF also reduces Clostridium-mediated 7α-dehydroxylation activity. All volunteers tolerated DSF well and there were no serious adverse events in the 7-day follow-up period. Transferring fecal microbiota obtained from DSF-treated humans into germ-free mice ameliorates NASH. Collectively, the observations of similar ameliorating effects of DSF on mice and humans suggest that DSF ameliorates NASH by modulating the gut microbiota and bile acid metabolism. Nonalcoholic steatohepatitis (NASH) has been linked with the gut-liver axis. Here, the authors show that disulfiram (DSF) reduces Clostridium-mediated 7α-dehydroxylation activity to suppress secondary bile acid biosynthesis and ameliorate NASH in mice, and validate DSF regulation of the gut-liver axis in healthy men in a self-controlled clinical trial. [ABSTRACT FROM AUTHOR]

Multi-view clustering is an important and challenging task in machine learning and data mining. In the past decade, this topic attracted much attention and there have been many progress achieved in this field. However, in reality, due to different factors such as machine error, sensor failure, multi-view data are mostly incomplete, thus how to deal with this problem becomes a challenge. Some existing works mainly deal with view missing case, which means in certain view of datasets, the whole features of some samples would be lost. In fact, missing value can occur in any position, that is, any value missing case. In that case, there would be some values missed in any view with sheerly random way. We proposed a two-stage algorithm involved multiple imputation and ensemble clustering to deal with multi-view clustering in any value missing case. Multiple imputation is adopted to deal with missing values problem and weighted ensemble clustering is applied to implement multi-view clustering. The experimental comparison on several data sets verified the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate our experience in the treatment of petrous bone cholesteatoma (PBC). Methods: Data of PBC patients in our hospital from January 2000 to December 2019 were collected. Surgical approaches and facial function were mainly discussed and compared with the literature. The management of 2 giant PBC cases affecting rhinopharynx has been demonstrated. Results: The supralabyrinthine type was the most frequent type followed by the massive type. There were 5 cases with cholesteatoma extending into the clivus (2 cases), sphenoid (1 case) and rhinopharynx (2 cases). The translabyrinthine approach (40%) was our most frequently used approach followed by the middle fossa approach (36%) and the transmastoid approach (11%). There were 10 cases managed with the assistance of endoscope, including 3 cases with cholesteatoma extending into clivus, sphenoid and rhinopharynx separately. Obliteration of the cavity was performed in 70.3% (135/192) cases; 3 of them recurred. For the 2 giant PBC cases affecting rhinopharynx, traditional microscopic surgery assisted with transnasal endoscope was performed. The reduced exposure was beneficial for postoperative recovery, and the approach in the nasal cavity provided a permanent drainage for postoperative examination. Conclusion: Otologic endoscope combined with traditional microscopic surgery could reduce the exposure in surgery. For extremely extended cases of PBC, supplementary transnasal endoscopic approach deserves to be considered for the traditional temporal bone approach. [ABSTRACT FROM AUTHOR]

The weld forming characteristics of GMAW-based additive manufacturing on curved surface are dramatically influenced by gravity. Large inclined angle of the forming surface would lead to severe defects such as hump bead. In this paper, a computational model of welding molten pool flow dynamics was established to research the forming characteristic and control method of weld bead forming on cured surface, and deposition experiments were conducted to verify the proposed model. Results indicated that the velocity of backward flows increased with the increase of weld bead tilt angle (α) and irregular hump defects appeared when α > 60° for upward welding. The interaction between the downward squeezing force of the excess liquid at the top and the recoil force of the upward flow at the bottom and the surface tension were primary factors for welding hump formation. For downward welding, a good morphology shape could be obtained, and the weld height decreased and the weld width increased with the increase of weld bead tilt angle. Based on the molten behaviors and forming characteristics on curved surface for downward and upward welding, the method of deposition with weave welding was proposed to control hump defects. Gravity component in the welding direction was significantly reduced due to the change of forming trajectory, which improved the stability of the molten pool flow and was beneficial to obtain stable and consistent weld bead on complex surface. The dimensional deviations of the single bead between downward and upward welding were within 7% and the fluctuation deviation of the bead in multi-bead overlapping deposition with mixing downward and upward welding was 0.45, which could be acceptable in GMAW-based additive manufacturing process. These findings contributed to the weld bead forming control of curve layered additive manufacturing based on GMAW. [ABSTRACT FROM AUTHOR]

Background: Hand motion analysis by video recording during surgery has potential for evaluation of surgical performance. The aim was to identify how technical skill during open surgery can be measured unobtrusively by video recording during a surgical procedure. We hypothesized that procedural-step timing, hand movements, instrument use and Shannon entropy differ with expertise and training and are concordant with a performance-based validated individual procedure score. Methods: Surgeon and non-surgeon participants with varying training and levels of expertise were video recorded performing axillary artery exposure and control (AA) on un-preserved cadavers. Color-coded gloves permitted motion-tracking and automated extraction of entropy data from recordings. Timing and instrument-use metrics were obtained through observational video reviews. Shannon entropy measured speed, acceleration and direction by computer-vision algorithms. Findings were compared with individual procedure score for AA performance Results: Experts had lowest entropy values, idle time, active time and shorter time to divide pectoralis minor, using fewer instruments. Residents improved with training, without reaching expert levels, and showed deterioration 12–18 months later. Individual procedure scores mirrored these results. Non-surgeons differed substantially. Conclusions: Hand motion entropy and timing metrics discriminate levels of surgical skill and training, and these findings are congruent with individual procedure score evaluations. These measures can be collected using consumer-level cameras and analyzed automatically with free software. Hand motion with video timing data may have widespread application to evaluate resident performance and can contribute to the range of evaluation and testing modalities available to educators, training course designers and surgical quality assurance programs. [ABSTRACT FROM AUTHOR]

Purpose: The arterial pressure waveform is a composite of multiple interactions, and there may be more sensitive and specific features associated with hemorrhagic shock and intravascular volume depletion than systolic and/or diastolic blood pressure (BP) alone. The aim of this study was to characterize the arterial pressure waveform in differing grades of hemorrhage. Methods: Ten anesthetized swine (70–90 kg) underwent a 40% controlled exponential hemorrhage. High-fidelity arterial waveform data were collected (500 Hz) and signal-processing techniques were used to extract key features. Regression modeling was used to assess the trend over time. Short-time Fourier transform (STFT) was utilized to assess waveform frequency and power spectrum density variance. Results: All animals tolerated instrumentation and hemorrhage. The primary antegrade wave (P1) was relatively preserved while the renal (P2) and iliac (P3) reflection waves became noticeably attenuated during progressive hemorrhage. Several features mirrored changes in systolic and diastolic BP and plateaued at approximately 20% hemorrhage, and were best fit with non-linear sigmoidal regression modeling. The P1:P3 ratio continued to change during progressive hemorrhage (R2 = 0.51). Analysis of the first three harmonics during progressive hemorrhage via STFT demonstrated increasing variance with high coefficients of determination using linear regression in frequency (R2 = 0.70, 0.93, and 0.76, respectively) and power spectrum density (R2 = 0.90, 0.90, and 0.59, respectively). Conclusions: In this swine model of volume-controlled hemorrhage, hypotension was a predominating early feature. While most waveform features mirrored those of BP, specific features such as the variance may be able to distinguish differing magnitudes of hemorrhage despite little change in conventional measures. [ABSTRACT FROM AUTHOR]

Purpose: Aortic occlusion (AO) increases proximal perfusion and may improve rates of return of spontaneous circulation (ROSC). The objective of this study was to investigate the hemodynamic effects of cardiopulmonary resuscitation (CPR) and AO by REBOA on patients in traumatic cardiac arrest. Methods: Patients admitted between February 2013 and May 2017 at a tertiary center who suffered traumatic arrest, had an arterial line placed during resuscitation, and received CPR and REBOA which were included. In-hospital CPR data were obtained from videography. Arterial waveforms were recorded at 240 Hz. Results: 11 consecutive patients were included, 82% male; mean (± SD) age 37 ± 19 years. 55% suffered blunt trauma and the remaining penetrating injuries. 64% arrested out of hospital. During compressions with AO, the mean systolic blood pressure (SBP) was 70 ± 22 mmHg, mean arterial pressure (MAP) 43 ± 19 mmHg, and diastolic blood pressure (DBP) 26 ± 17 mmHg. Nine (82%) had ROSC, with eight having multiple periods of ROSC and arrest in the initial period. In-hospital mortality was 82%. Cardiac ultrasonography was used during arrest in 73%. In two patients with arterial line data before and after AO, SBP (mmHg) improved from 51 to 73 and 55 to 96 during arrest after AO. Conclusions: High-quality chest compressions coupled with aortic occlusion may generate adequate perfusion pressures to increase the rate of ROSC. New technology capable of transducing central arterial pressure may help us to understand the effectiveness of CPR with and without aortic occlusion. REBOA may be a useful adjunct to high-quality chest compressions during arrest. [ABSTRACT FROM AUTHOR]

Objective: To describe the operative findings and surgical results of unilateral congenital middle ear malformations with intact external ear.Methods: A retrospective review was performed on 64 patients with unilateral congenital middle ear malformations and intact external ear who underwent exploratory tympanotomy from 2011 to 2016. Demographic data, clinical data, high-resolution computed tomography findings, audiometric data and intraoperative findings were collected. Audiological evaluations before and 6 months after surgery were analyzed in 47 patients.Results: The most common malformation were mobile stapes with missing incus long process and stapes suprastructure. The air conduction pure tone average was 58.9 ± 10.5 dB HL (range 34.4-78.1 dB HL) preoperatively and 28.8 ± 10.6 dB HL (range 9.4-55.6 dB HL) postoperatively (P = 0.000). Twenty-five cases (53.2%) acquired an air conduction hearing gain exceeding 30 dB. Mean air-bone gap (ABG) was 44.5 ± 9.4 dB (range 22.5-66.4 dB HL) before surgery and 15.6 ± 9.3 dB (range 0-35.6 dB) after surgery (P = 0.000) for an average gain of 28.8 ± 11.5 dB. Thirty-four cases (72.3%) showed a postoperative ABG of less than 20 dB, 15 had an ABG within 10 dB, and 4 had 0 dB ABG after operation. No significant difference was observed for air conduction hearing gain regarding age (P = 0.261) or types of malformations (mobile stapes footplate with or without a suprastructure anomaly, P = 0.058).Conclusion: Unilateral congenital middle ear malformations with intact external ear can be complex and diverse. Functional ossiculoplasty for patients with unilateral congenital middle ear malformations can achieve good hearing outcomes. [ABSTRACT FROM AUTHOR]

Objective: Although the endoscopic treatment of gastric stromal tumors is a recently accepted therapy, the long-term outcomes of this approach remain unknown. The aims of this study were to assess the long-term effectiveness and safety of endoscopic resection for gastric GISTs.Methods: A total of 60 consecutive patients undergoing endoscopic resection of gastric GISTs were enrolled in a retrospective single-center study. Clinical data, perioperative complications, histopathologic characteristics of the tumors, and long-term outcomes were recorded.Results: Sixty patients successfully underwent complete resection of lesions, including 25 cases of endoscopic submucosal dissection (ESD) and 35 cases of endoscopic full-thickness resection (EFTR), with an average tumor size of 1.76 ± 1.55 cm (range 0.5-7.6 cm). The average operation time was 43.97 ± 26.95 min (range 11.7-138.9 min). Two cases were observed with an intraoperative hemorrhage of 200 mL, which were successfully managed by hemostatic forceps. Perforations of 2-11 mm of ESD occurred in four cases (4/25) and were well closed with endoclips, with no conversions to surgical operation. Mucosal laceration of esophagus occurred in 1 case, when a large tumor was removed. The average length of hospitalization was 6.50 ± 3.06 days (range 3-21 days). Out of a total of 60 patients, 44 (73.3%) were at very low risk, 10 (16.7%) were at low risk, 5 (8.3%) were at intermediate risk, and 1 (1.7%) was at high risk. All patients were followed-up for 36.15 ± 12.92 months (range 14-73 months). Primary tumor recurrence occurred in 1 patient who underwent a second operation after 32 months, and no other cases were observed to have either tumor recurrence or metastasis.Conclusions: For long-term outcomes, endoscopic resection of ESD or EFTR is a safe and effective approach for removing gastric stromal tumors (<5 cm), and it can be a resection technique for them with no metastasis. [ABSTRACT FROM AUTHOR]

Respiratory rate (RR) is important in many patient care settings; however, direct observation of RR is cumbersome and often inaccurate, and electrocardiogram-derived RR (RRECG) is unreliable. We asked how data derived from the first 15 min of RR recording after trauma center admission using a novel acoustic sensor (RRa) would compare to RRECG and to end-tidal carbon dioxide-based RR ([Formula: see text]) from intubated patients, the "gold standard" in predicting life-saving interventions in unstable trauma patients. In a convenience sample subset of trauma patients admitted to our Level 1 trauma center, enrolled in the ONPOINT study, and monitored with RRECG, some of whom also had [Formula: see text] data, we collected RRa using an adhesive sensor with an integrated acoustic transducer (Masimo RRa™). Using Bland-Altman analysis of area under the receiver operating characteristic (AUROC) curves, we compared the first 15 min of continuous RRa and RRECG to [Formula: see text] and assessed the performance of these three parameters compared to the Revised Trauma Score (RTS) in predicting blood transfusion 3, 6, and 12 h after admission. Of the 1200 patients enrolled in ONPOINT from December 2011 to May 2013, 1191 had RRECG data recorded in the first 15 min, 358 had acoustic monitoring, and 14 of the latter also had [Formula: see text]. The three groups did not differ demographically or in mechanism of injury. RRa showed less bias (0.8 vs. 6.9) and better agreement than RRECG when compared to [Formula: see text]. At [Formula: see text] 10-29 breaths per minute, RRa was more likely to be the same as [Formula: see text] and assign the same RTS. In predicting transfusion, features derived from RRa and RRECG gave AUROCs 0.59-0.66 but with true positive rate 0.70-0.89. RRa monitoring is a non-invasive option to glean valid RR data to assist clinical decision making and could contribute to prediction models in non-intubated unstable trauma patients. [ABSTRACT FROM AUTHOR]

The spiral ganglion neurons (SGNs) located in the Rosenthal's canal of cochlea are essential target for cochlear implant. Previous studies found that the canaliculi perforantes, small pores on the surface of the osseous spiral lamina (OSL) of the scala tympanic (ST) of cochlea, may provide communication between the cochlear perilymph and SGNs. In this study, we found that chronic treatment of aminoglycosides antibiotics, which is well known to cause sensory cell damage in the cochlea, induced significant damage of bone lining cells on the OSLs and increased the permeability of the Rosenthal's canal. The pores among the bone lining cells became significantly wider after chronic treatment of amikacin (100 mg/kg/day for 3-7 days). Injection of Evans Blue in the ST resulted in significant increase in its migration in the modulus in the amikacin-treated cochlea compared to the control ears, suggesting increased permeability of these passages. Treatment of amikacin with oxytetracycline, an inhibitor of matrix metalloproteases (MMPs), significantly reduced the amount of dye migrated from the ST to the modiolus. These results suggest that amikacin enhanced the permeability between the ST and SGNs by increasing MMPs. Aggregating the permeability of the bone lining cells on the OSLs may benefit gene and stem cell delivery to the SGNs in the cochlea. [ABSTRACT FROM AUTHOR]

Research and practice based on automated electronic patient monitoring and data collection systems is significantly limited by system down time. We asked whether a triple-redundant Monitor of Monitors System (MoMs) to collect and summarize key information from system-wide data sources could achieve high fault tolerance, early diagnosis of system failure, and improve data collection rates. In our Level I trauma center, patient vital signs(VS) monitors were networked to collect real time patient physiologic data streams from 94 bed units in our various resuscitation, operating, and critical care units. To minimize the impact of server collection failure, three BedMaster® VS servers were used in parallel to collect data from all bed units. To locate and diagnose system failures, we summarized critical information from high throughput datastreams in real-time in a dashboard viewer and compared the before and post MoMs phases to evaluate data collection performance as availability time, active collection rates, and gap duration, occurrence, and categories. Single-server collection rates in the 3-month period before MoMs deployment ranged from 27.8 % to 40.5 % with combined 79.1 % collection rate. Reasons for gaps included collection server failure, software instability, individual bed setting inconsistency, and monitor servicing. In the 6-month post MoMs deployment period, average collection rates were 99.9 %. A triple redundant patient data collection system with real-time diagnostic information summarization and representation improved the reliability of massive clinical data collection to nearly 100 % in a Level I trauma center. Such data collection framework may also increase the automation level of hospital-wise information aggregation for optimal allocation of health care resources. [ABSTRACT FROM AUTHOR]

Fibrosis, closely related to chronic various diseases, is a pathological process characterised by the accumulation of collagen (largely collagen type I). Non-invasive methods are necessary for the diagnosis and follow-up of fibrosis. This study aimed to develop a collagen-targeted probe for the molecular imaging of fibrosis. We identified CPKESCNLFVLKD (CBP1495) as an original collagen-binding peptide using isothermal titration calorimetry and enzyme-linked immunosorbent assay. CBP1495 effectively bound to collagen type I ( K = 861 nM) and (GPO) ( K = 633 nM), a collagen mimetic peptide. Western blot and histochemistry validated CBP1495 targeting collagen in vitro and ex vivo. (Gly-( D)-Ala-Gly-Gly) was introduced to CBP1495 for coupling Tc. Labelling efficiency of Tc-CBP1495 was 95.06 ± 1.08 %. The physico-chemical properties, tracer kinetics and biodistribution of Tc-CBP1495 were carried out, and showed that the peptide stably chelated Tc in vitro and in vivo. SPECT/CT imaging with Tc-CBP1495 was performed in rat fibrosis models, and revealed that Tc-CBP1495 significantly accumulated in fibrotic lungs or livers of rats. Finally, Tc-CBP1495 uptake and hydroxyproline (Hyp), a specific amino acid of collagen, were quantitatively analysed. The results demonstrated that Tc-CBP1495 uptake was positvely correlated with Hyp content in lungs ( P < 0.0001, r = 0.8266) or livers ( P < 0.0001, r = 0.7581). Therefore, CBP1495 is a novel collagen-binding peptide, and Tc-labelled CBP1495 may be a promising radiotracer for the molecular imaging of fibrosis. [ABSTRACT FROM AUTHOR]

More than 100 genes have been associated with deafness. However, SMAD4 is rarely considered a contributor to deafness in humans, except for its well-defined role in cell differentiation and regeneration. Here, we report that a SMAD4 defect in mice can cause auditory neuropathy, which was defined as a mysterious hearing and speech perception disorder in human for which the genetic background remains unclear. Our study showed that a SMAD4 defect induces failed formation of cochlear ribbon synapse during the earlier stage of auditory development in mice. Further investigation found that there are nearly normal morphology of outer hair cells (OHCs) and post-synapse spiral ganglion nerves (SGNs) in SMAD4 conditional knockout mice (cKO); however, a preserved distortion product of otoacoustic emission (DPOAE) and cochlear microphonic (CM) still can be evoked in cKO mice. Moreover, a partial restoration of hearing detected by electric auditory brainstem response (eABR) has been obtained in the cKO mice using electrode stimuli toward auditory nerves. Additionally, the ribbon synapses in retina are not affected by this SMAD4 defect. Thus, our findings suggest that this SMAD4 defect causes auditory neuropathy via specialized disruption of cochlear ribbon synapses. [ABSTRACT FROM AUTHOR]

Ototoxicity is one of the major causes of sensorineural deafness. However, it remains unclear whether sensorineural deafness is reversible after ototoxic withdrawal. Here, we report that the ribbon synapses between the inner hair cells (IHCs) and spiral ganglion nerve (SGN) fibers can be restored after ototoxic trauma. This corresponds with hearing restoration after ototoxic withdrawal. In this study, adult mice were injected daily with a low dose of gentamicin for 14 consecutive days. Immunostaining for RIBEYE/CtBP2 was used to estimate the number and size of synaptic ribbons in the cochlea. Hearing thresholds were assessed using auditory brainstem responses. Auditory temporal processing between IHCs and SGNs was evaluated by compound action potentials. We found automatic hearing restoration after ototoxicity withdrawal, which corresponded to the number and size recovery of synaptic ribbons, although both hearing and synaptic recovery were not complete. Thus, our study indicates that sensorineural deafness in mice can be reversible after ototoxic withdrawal due to an intrinsic repair of ribbon synapse in the cochlea. [ABSTRACT FROM AUTHOR]

Early detection of hemorrhagic shock is required to facilitate prompt coordination of blood component therapy delivery to the bedside and to expedite performance of lifesaving interventions. Standard physical findings and vital signs are difficult to measure during the acute resuscitation stage, and these measures are often inaccurate until patients deteriorate to a state of decompensated shock. The aim of this study is to examine a severely injured trauma patient population to determine whether a noninvasive SpHb monitor can predict the need for urgent blood transfusion (universal donor or additional urgent blood transfusion) during the first 12 h of trauma patient resuscitation. We hypothesize that trends in continuous SpHb, combined with easily derived patient-specific factors, can identify the immediate need for transfusion in trauma patients. Subjects were enrolled if directly admitted to the trauma center, >17 years of age, and with a shock index (heart rate/systolic blood pressure) >0.62. Upon admission, a Masimo Radical-7 co-oximeter sensor (Masimo Corporation, Irvine, CA) was applied, providing measurement of continuous non-invasive hemoglobin (SpHb) levels. Blood was drawn and hemoglobin concentration analyzed and conventional pulse oximetry photopletysmograph signals were continuously recorded. Demographic information and both prehospital and admission vital signs were collected. The primary outcome was transfusion of at least one unit of packed red blood cells within 24 h of admission. Eight regression models (C1-C8) were evaluated for the prediction of blood use by comparing area under receiver operating curve (AUROC) at different time intervals after admission. 711 subjects had continuous vital signs waveforms available, to include heart rate (HR), SpHb and SpO2 trends. When SpHb was monitored for 15 min, SpHb did not increase AUROC for prediction of transfusion. The highest ROC was recorded for model C8 (age, sex, prehospital shock index, admission HR, SpHb and SpO2) for the prediction of blood products within the first 3 h of admission. When data from 15 min of continuous monitoring were analyzed, significant improvement in AUROC occurred as more variables were added to the model; however, the addition of SpHb to any of the models did not improve AUROC significantly for prediction of blood use within the first 3 h of admission in comparison to analysis of conventional oximetry features. The results demonstrate that SpHb monitoring, accompanied by continuous vital signs data and adjusted for age and sex, has good accuracy for the prediction of need for transfusion; however, as an independent variable, SpHb did not enhance predictive models in comparison to use of features extracted from conventional pulse oximetry. Nor was shock index better than conventional oximetry at discriminating hemorrhaging and prediction of casualties receiving blood. In this population of trauma patients, noninvasive SpHb monitoring, including both trends and absolute values, did not enhance the ability to predict the need for blood transfusion. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "De novo mutation in ATP6V1B2 impairs lysosome acidification and causes dominant deafness-onychodystrophy syndrome" in the June 10, 2014 issue.

To identify genetic markers for laryngeal squamous cell carcinoma (LSCC), we conducted a genome-wide association study (GWAS) on 993 individuals with LSCC (cases) and 1,995 cancer-free controls from Chinese populations. The most promising variants (association P < 1 × 10−5) were then replicated in 3 independent sets including 2,398 cases and 2,804 controls, among which we identified 3 new susceptibility loci at 11q12 (rs174549), 6p21 (rs2857595) and 12q24 (rs10492336). The minor alleles of each of these loci showed protective effects, with odds ratios (95% confidence intervals) of 0.73 (0.68-0.78; P = 1.00 × 10−20), 0.78 (0.72-0.84; P = 2.43 × 10−15) and 0.71 (0.65-0.77; P = 4.48 × 10−14), respectively. None of these variants showed an interaction with smoking or drinking. This is the first GWAS to our knowledge solely on LSCC, and the findings might advance understanding of the etiology of LSCC. [ABSTRACT FROM AUTHOR]

The ribbon synapses of inner hair cells (IHCs) play an important role in sound encoding and neurotransmitter release. However, it remains unclear whether IHC ribbon synapse plasticity can be interrupted by ototoxic aminoglycoside stimuli. Here, we report that quantitative changes in the number of IHC ribbon synapses and hearing loss occur in response to gentamicin treatment in mice. Using 3D reconstruction, we were able to calculate the number of IHC ribbon synapses after ototoxic gentamicin exposure. Mice were injected intraperitoneally with a low dose of gentamicin (100 mg/kg) once a day for 14 days. Double immunostaining was used to identify IHC ribbon synapses; histopathology and scanning electron microscopy were used to observe the morphology of cochlear hair cells and spiral ganglion neurons (SGNs), the hearing threshold shifts were recorded by auditory brainstem response examinations. Our study shows that the maximal number of IHC ribbon synapses appeared at the 7th day after treatment, followed by a significant reduction after the 7th day regardless of ongoing treatment. Correspondingly, the maximal elevation of hearing threshold was observed at the 7th day after treatment. Meanwhile, additional cochlear components included OHCs, IHCs, and SGNs were unaffected, suggesting that IHC ribbon synapses are more susceptible to ototoxic aminoglycoside stimulation. Our study indicated that quantitative changes in the number of IHC ribbon synapses is critical response to lower dose of ototoxic stimulation, and may contribute to moderate hearing loss. Additionally, our data indcated that ribbon synaptic plasticity may require the quantitative changes to play self-protective role adapted to ototoxic aminoglycoside stimuli. [ABSTRACT FROM AUTHOR]

The objective is to study the therapeutic effects of Gushen Pian on sensorineural deafness according to the Phase II clinical trial protocol, as approved for novel traditional Chinese medicines by Ministry of Health of PRC. This is a double blind study in which 120 patients were allocated randomly into treatment and control groups and an open treatment group (40 cases in each group). Patients in the treatment groups were administrated with Gushen Pian and controls received placebo. Routine examination of blood and urine, hepatic and renal function tests and pure tone audiometry were performed before and after treatment. Clinical symptoms and therapeutic outcomes were compared and evaluated. For double-blind treatment group, the total effective rate of deafness was 42.2 % and total relieved rate of deafness was 4.6 %; for double-blind control group, the total effective rate of deafness was 18.7 % and total relieved rate of deafness was 0 %; for simple treatment group, the total effective rate of deafness was 58.7 % and total relieved rate of deafness was 6.3 %. For double-blind treatment group, the total effective rate of tinnitus was 89.2 % and total relieved rate of tinnitus was 59.5 %; for double-blind control group, the total effective rate of tinnitus was 30.8 % and total relieved rate of tinnitus was 5.1 %; for simple treatment group, the total effective rate of tinnitus was 74.3 % and total relieved rate of tinnitus was 57.1 %. The double-blind treatment showed statistically significant differences from control group. The medication could effectively alleviate aural fullness, dizziness, lassitude of loins and knees, dysphoria with feverish sensation in chest, insomnia, and fatigue, etc. No adverse effect was reported during treatment; no abnormal results were reported in blood, urine, faces, heart function, liver function and kidney function examination. Gushen Pian had beneficial effect on deafness and tinnitus and could effectively alleviate aural fullness, insomnia, etc., without any adverse effects. [ABSTRACT FROM AUTHOR]

The different cell types within the cochlea may have a specific contribution to the pathological changes during metabolism failure, which may provide clues for developing novel strategies for inner ear therapy. In order to evaluate activity-correlated cell death during metabolism failure in the cochlea, 3-nitropropionic acid was used to irreversibly inhibit the respiratory chain. Dose-response of the cochlear cells to 3-nitropropionic acid was analyzed in vitro. 3-Nitropropionic acid was administered onto the round window of guinea pigs. Cell death was identified by terminal transferase labeling the free 3′OH breaks in the DNA strands in vivo and propidium iodide nuclear permeation in vitro. As a result, 23.6 and 96.3 % cell death were induced by 10 and 100 mM 3-nitropropionic acid, respectively, in vitro. In the guinea pigs, 500 mM 3-nitropropionic acid induced vestibular dysfunction and severe to profound hearing losses. The cells that are the most sensitive to 3-nitropropionic acid treatment include the stria marginal and intermediate cells, epithelial cells of the Reissner's membrane, and spiral ligament fibrocytes (types II and V). Moderate sensitive cells were satellite fibrocytes of the spiral limbic central zone, osteocytes of the cochlear shell, hair cells, and spiral ganglion cells. Reduction of neurofilament in the soma and periphery processes of spiral ganglion cells occurred after the exposure. These results may be relevant to the mechanisms of injury in sudden onset sensorineural hearing loss and hazardous substance exposure-induced hearing loss. [ABSTRACT FROM AUTHOR]

Background: We asked whether continuous intracranial pressure (ICP) monitoring data could provide objective measures of the degree and timing of intracranial hypertension (ICH) in the first week of neurotrauma critical care and whether such data could be linked to outcome. Methods: We enrolled adult (>17 years old) patients admitted to our Level I trauma center within 6 h of severe TBI. ICP data were automatically captured and ICP 5-minute means were grouped into 12-hour time periods from admission (hour 0) to >7 days (hour 180). Means, maximum, percent time (% time), and pressure-times-time dose (PTD, mmHg h) of ICP >20 mmHg and >30 mmHg were calculated for each time period. Results: From 2008 to 2010, we enrolled 191 patients. Only 2.1 % had no episodes of ICH. The timing of maximum PTD was relatively equally distributed across the 15 time periods. Median ICP, PTD, %time, and %time were all significantly higher in the 84-180 h time period than the 0-84 h time period. Stratified by functional outcome, those with poor functional outcome had significantly more ICH in hours 84-180. Multivariate analysis revealed that, after 84 h of monitoring, every 5 % increase in PTD was independently associated with 21 % higher odds of having a poor functional outcome (adjusted odds ratio = 1.21, 95 % CI 1.02-1.42, p = 0.03). Conclusions: Although early elevations in ICP occur, ICPs are the highest later in the hospital course than previously understood, and temporal patterns of ICP elevation are associated with functional outcome. Understanding this temporal nature of secondary insults has significant implications for management. [ABSTRACT FROM AUTHOR]

Bone marrow-derived stem cells (BMDCs) have the ability to differentiate into lung epithelial cells in response to damage; however, their role in squamous cell carcinoma (SCC) formation is unknown. This study aimed to determine whether BMDC-derived lung epithelial cells could contribute to SCC formation. A model of lung SCC induced with N-nitrosodiethylamine (NDEA) in recipient female mice transplanted with green fluorescent protein (GFP)-positive BMDCs from male donors was established. Incorporation of BMDCs in lung tissue was determined using immunohistochemistry and immunofluorescence to detect GFP expression and fluorescence in situ hybridization to Y chromosomes. BMDC appeared at three stages of lung SCC progression: metaplasia, dysplasia, and carcinoma. There was a significantly higher proportion of GFP-positive (GFP) cells within SCC than was found in metaplasia and dysplasia 16 weeks post-transplantation (both P < 0.017); GFP BMDCs were also observed in clusters within several SCC nests. Furthermore, most GFP cells in SCC were pancytokeratin-positive (PCK) epithelial cells, and some exhibited proliferative activity as determined by Ki67 staining (9.7 ± 3.92 %). The presence of GFPKi67PCK cells within SCC nests suggested that some donor BMDCs differentiated into proliferating epithelial cells. Finally, analysis of p63 expression, a marker of SCC cells, indicated that the presence of GFPp63 cells (green) in inner parts of the SCC. These findings strongly suggest that BMDC-derived lung epithelial cells could participate in lung SCC formation and partially contribute to tumor growth, which might have significant potential implications for both clinical cancer therapy using BMDCs. [ABSTRACT FROM AUTHOR]

Subtle and profound changes in autonomic nervous system (ANS) function affecting sympathetic and parasympathetic homeostasis occur as a result of critical illness. Changes in ANS function are particularly salient in neurocritical illness, when direct structural and functional perturbations to autonomic network pathways occur and may herald impending clinical deterioration or intervenable evolving mechanisms of secondary injury. Sympathetic and parasympathetic balance can be measured quantitatively at the bedside using multiple methods, most readily by extracting data from electrocardiographic or photoplethysmography waveforms. Work from our group and others has demonstrated that data-analytic techniques can identify quantitative physiologic changes that precede clinical detection of meaningful events, and therefore may provide an important window for time-sensitive therapies. Here, we review data-analytic approaches to measuring ANS dysfunction from routine bedside physiologic data streams and integrating this data into multimodal machine learning-based model development to better understand phenotypical expression of pathophysiologic mechanisms and perhaps even serve as early detection signals. Attention will be given to examples from our work in acute traumatic brain injury on detection and monitoring of paroxysmal sympathetic hyperactivity and prediction of neurologic deterioration, and in large hemispheric infarction on prediction of malignant cerebral edema. We also discuss future clinical applications and data-analytic challenges and future directions. [ABSTRACT FROM AUTHOR]

Aims: Livestock grazing greatly affects the soil environments and soil microbial community, potentially driving significant biodiversity losses. Yet, how soil microbial communities respond to grazing remains relatively unknown in southern grasslands. This study hypothesized that long-term grazing alters soil microbial community composition and reduces microbial diversity by changing underlying soil properties.To assess the impact of long-term grazing on soil properties, bacterial and fungal diversity and microbial community composition were investigated in replicate grazed (38 years of moderate intensity grazing) and ungrazed plots in a subtropical grassland, China.Fungal β-diversity was more sensitive to long-term grazing than bacterial β-diversity, with fungal β-diversity decreasing by 28.8%. No significant differences in soil bacterial or fungal α-diversity were detected between grazed and ungrazed plots. Additionally, long-term grazing altered microbial community composition, altering the relative abundance of specific microbial taxa. For bacteria, the relative abundance of Actinobacteriota (41.9%) increased and Acidobacteriota decreased (−22.3%). For fungi, grazing increased the relative abundance of Mortierellomycota (108.1%) and decreased Basidiomycota (−79.5%). Changes in both bacterial and fungal community composition were well explained by available phosphorus, dissolved organic nitrogen, dissolved organic carbon, soil organic carbon, total soil nitrogen, and NH4+-N.Our study showed that fungal β-diversity decreased after long-term grazing, necessitating changes to grazing management practices to foster soil biodiversity conservation and functions in southern grasslands.Methods: Livestock grazing greatly affects the soil environments and soil microbial community, potentially driving significant biodiversity losses. Yet, how soil microbial communities respond to grazing remains relatively unknown in southern grasslands. This study hypothesized that long-term grazing alters soil microbial community composition and reduces microbial diversity by changing underlying soil properties.To assess the impact of long-term grazing on soil properties, bacterial and fungal diversity and microbial community composition were investigated in replicate grazed (38 years of moderate intensity grazing) and ungrazed plots in a subtropical grassland, China.Fungal β-diversity was more sensitive to long-term grazing than bacterial β-diversity, with fungal β-diversity decreasing by 28.8%. No significant differences in soil bacterial or fungal α-diversity were detected between grazed and ungrazed plots. Additionally, long-term grazing altered microbial community composition, altering the relative abundance of specific microbial taxa. For bacteria, the relative abundance of Actinobacteriota (41.9%) increased and Acidobacteriota decreased (−22.3%). For fungi, grazing increased the relative abundance of Mortierellomycota (108.1%) and decreased Basidiomycota (−79.5%). Changes in both bacterial and fungal community composition were well explained by available phosphorus, dissolved organic nitrogen, dissolved organic carbon, soil organic carbon, total soil nitrogen, and NH4+-N.Our study showed that fungal β-diversity decreased after long-term grazing, necessitating changes to grazing management practices to foster soil biodiversity conservation and functions in southern grasslands.Results: Livestock grazing greatly affects the soil environments and soil microbial community, potentially driving significant biodiversity losses. Yet, how soil microbial communities respond to grazing remains relatively unknown in southern grasslands. This study hypothesized that long-term grazing alters soil microbial community composition and reduces microbial diversity by changing underlying soil properties.To assess the impact of long-term grazing on soil properties, bacterial and fungal diversity and microbial community composition were investigated in replicate grazed (38 years of moderate intensity grazing) and ungrazed plots in a subtropical grassland, China.Fungal β-diversity was more sensitive to long-term grazing than bacterial β-diversity, with fungal β-diversity decreasing by 28.8%. No significant differences in soil bacterial or fungal α-diversity were detected between grazed and ungrazed plots. Additionally, long-term grazing altered microbial community composition, altering the relative abundance of specific microbial taxa. For bacteria, the relative abundance of Actinobacteriota (41.9%) increased and Acidobacteriota decreased (−22.3%). For fungi, grazing increased the relative abundance of Mortierellomycota (108.1%) and decreased Basidiomycota (−79.5%). Changes in both bacterial and fungal community composition were well explained by available phosphorus, dissolved organic nitrogen, dissolved organic carbon, soil organic carbon, total soil nitrogen, and NH4+-N.Our study showed that fungal β-diversity decreased after long-term grazing, necessitating changes to grazing management practices to foster soil biodiversity conservation and functions in southern grasslands.Conclusions: Livestock grazing greatly affects the soil environments and soil microbial community, potentially driving significant biodiversity losses. Yet, how soil microbial communities respond to grazing remains relatively unknown in southern grasslands. This study hypothesized that long-term grazing alters soil microbial community composition and reduces microbial diversity by changing underlying soil properties.To assess the impact of long-term grazing on soil properties, bacterial and fungal diversity and microbial community composition were investigated in replicate grazed (38 years of moderate intensity grazing) and ungrazed plots in a subtropical grassland, China.Fungal β-diversity was more sensitive to long-term grazing than bacterial β-diversity, with fungal β-diversity decreasing by 28.8%. No significant differences in soil bacterial or fungal α-diversity were detected between grazed and ungrazed plots. Additionally, long-term grazing altered microbial community composition, altering the relative abundance of specific microbial taxa. For bacteria, the relative abundance of Actinobacteriota (41.9%) increased and Acidobacteriota decreased (−22.3%). For fungi, grazing increased the relative abundance of Mortierellomycota (108.1%) and decreased Basidiomycota (−79.5%). Changes in both bacterial and fungal community composition were well explained by available phosphorus, dissolved organic nitrogen, dissolved organic carbon, soil organic carbon, total soil nitrogen, and NH4+-N.Our study showed that fungal β-diversity decreased after long-term grazing, necessitating changes to grazing management practices to foster soil biodiversity conservation and functions in southern grasslands. [ABSTRACT FROM AUTHOR]