The risk factors for postoperative temporary vocal cord paralysis after thyroid cancer surgery: an observational retrospective cohort study.

OBJECTIVE: To analyze the potential factors influencing new-onset postoperative transient vocal cord paralysis (VCP) in thyroid cancer patients. METHODS: Case information of 8,340 thyroid cancer patients hospitalized at XX from January 2018 to December 2020 was collected retrospectively and analyzed. The possible influencing factors were analyzed using a chi-square test, rank-sum test, and multiple logistic regression analysis. A nomogram was used to construct the clinical prediction model that was validated in the validation set by ROC, calibration curves, and DCA. RESULTS: The STROCSS guideline was followed to conduct a retrospective cohort study. A total of 8,340 patients, including 1,817 (21.8%) men and 6,523 (78.2%) women, were enrolled in this study. The rate of temporary VCP was 3.6% (308/8,340). Based on the results of postoperative laryngoscopy, the patients were divided into VCP group and non-VCP group. Comparative analysis between the groups revealed that potential factors associated with postoperative transient VCP were tumor location on the dorsal side of the gland (P = 0.042), ultrasound showing a maximum nodal diameter > 1 cm (P = 0.002), multifocal carcinoma (P < 0.001), invasion of surrounding tissue (P = 0.005), lymph node metastases in the central compartment (P = 0.034), lateral cervical lymph node metastasis (P < 0.001), and prolonged operation (P < 0.001). A multiple logistic regression analysis showed that the independent risk factors in postoperative transient VCP were T stage (OR = 1.411, P = 0.013, 95% CI: 1.075-1.853), multifocal carcinoma (OR = 1.532, P = 0.013, 95% CI: 1.095-2.144), and duration of surgery (OR = 1.009, P < 0.001, 95% CI: 1.006-1.012). Finally, a clinical prediction model was established via a nomogram and was validated in the validation set, although its diagnostic efficacy needs to be improved further. CONCLUSION: High T stage, multifocal carcinoma, and prolonged operation time may be independent risk factors for the occurrence of postoperative transient VCP in patients undergoing initial surgery for thyroid cancer.

Chitosan synergizes with bismuth-based metal-organic frameworks to construct double S-type heterojunctions for enhancing photocatalytic antimicrobial activity.

In recent years, photocatalytic technology has been introduced to develop a new kind antimicrobial agents fighting antibiotic abusing and related drug resistance. The efforts have focused on non-precious metal photocatalysts along with green additives. In the present work, a novel bis-S heterojunctions based on the coupling of polysaccharide (CS) and bismuth-based MOF (CAU-17) s synthesized through a two-step method involving amidation reaction under mild conditions. The as prepared photocatalyst literally extended the light response to the near-infrared region. Owing to its double S-type heterostructure, the lifetime of the photocarriers is significantly prolonged and the redox capacity are enhanced. As a result, the as prepared photocatalyst indicated inhibition up to 99.9 % under 20 min of light exposure against Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria as well as drug-resistant bacteria (MRSA). The outstanding photocatalytic performance is attributed to the effective charge separation and migration due to the unique double S heterostructure. Such a double S heterostructure was confirmed through transient photocurrent response, electrochemical impedance spectroscopy tests and electron spin resonance measurements. The present work provides a basis for the simple synthesis of high-performance heterojunction photocatalytic inhibitors, which extends the application of CAU-17 in environmental disinfection and wastewater purification.

Noticeable effect of lower baseline amplitude on the predictive accuracy of intraoperative amplitude changes for postoperative vocal cord palsy: a prospective cohort study.

BACKGROUND: To explore the effect of lower baseline amplitude on its predictive accuracy of postoperative vocal cord paralysis (VCP) in monitored thyroid surgery. MATERIALS AND METHODS: Clinical and electrophysiological data were collected during thyroid surgeries performed between November and December 2021 at China-Japan Union Hospital. Univariate/multivariate regression analysis were applied to these data to examine a possible correlation. A receiver operating characteristic curve was used to evaluate predictive efficacy. RESULTS: A total of 631 nerves-at-risk (NAR) were identified in 460 patients who were divided into two groups according to postoperative development of VCP. The VCP group included a higher percentage of NAR with V1<1000 (68.2 vs. 40.7%, respectively; P =0.014) and NAR with R1<1400 (77.3 vs. 47.0%, respectively; P =0.005) compared with the non-VCP group. Multivariate regression analysis further identified V1<1000 [odds ratio (OR)=2.688, P =0.038], R1<1400 (OR=3.484, P =0.018) as independent risk factors for postoperative temporary VCP. The receiver operating characteristic curve showed the AUC value of V signal decline for predicting VCP was 0.87. The diagnostic efficiency of R signal decline reached as high as 0.973. A multivariate logistic regression analysis identified independent risk factors for V1<1000 and these included: higher BMI (OR=1.072, P =0.013), hypertension (OR=1.816, P =0.015), smoking (OR=1.814, P =0.031), and male sex (OR=2.016, P =0.027). CONCLUSION: In our cohort, lower baseline amplitude was an independent risk factor for developing transient postoperative VCP. It also affected the predictive efficacy of intraoperative amplitude changes on VCP. Higher BMI, hypertension, smoking, and male sex may also be closely associated with lower initial amplitude. Thus, maintaining a higher initial amplitude is critical for patient safety during thyroid surgery.

Sleep-phasic heart rate variability predicts stress severity: Building a machine learning-based stress prediction model.

We propose a novel approach for predicting stress severity by measuring sleep phasic heart rate variability (HRV) using a smart device. This device can potentially be applied for stress self-screening in large populations. Using a Holter electrocardiogram (ECG) and a Huawei smart device, we conducted 24-h dual recordings of 159 medical workers working regular shifts. Based on photoplethysmography (PPG) and accelerometer signals acquired by the Huawei smart device, we sorted episodes of cyclic alternating pattern (CAP; unstable sleep), non-cyclic alternating pattern (NCAP; stable sleep), wakefulness, and rapid eye movement (REM) sleep based on cardiopulmonary coupling (CPC) algorithms. We further calculated the HRV indices during NCAP, CAP and REM sleep episodes using both the Holter ECG and smart-device PPG signals. We later developed a machine learning model to predict stress severity based only on the smart device data obtained from the participants along with a clinical evaluation of emotion and stress conditions. Sleep phasic HRV indices predict individual stress severity with better performance in CAP or REM sleep than in NCAP. Using the smart device data only, the optimal machine learning-based stress prediction model exhibited accuracy of 80.3 %, sensitivity 87.2 %, and 63.9 % for specificity. Sleep phasic heart rate variability can be accurately evaluated using a smart device and subsequently can be used for stress predication.

Antimicrobial Hydrogels: Potential Materials for Medical Application.

Microbial infections based on drug-resistant pathogenic organisms following surgery or trauma and uncontrolled bleeding are the main causes of increased mortality from trauma worldwide. The prevalence of drug-resistant pathogens has led to a significant increase in medical costs and poses a great threat to the normal life of people. This is an important issue in the field of biomedicine, and the emergence of new antimicrobial materials hydrogels holds great promise for solving this problem. Hydrogel is an important material with good biocompatibility, water absorption, oxygen permeability, adhesion, degradation, self-healing, corrosion resistance, and controlled release of drugs as well as structural diversity. Bacteria-disturbing hydrogels have important applications in the direction of surgical treatment, wound dressing, medical device coating, and tissue engineering. This paper reviews the classification of antimicrobial hydrogels, the current status of research, and the potential of antimicrobial hydrogels for one application in biomedicine, and analyzes the current research of hydrogels in biomedical applications from five aspects: metal-loaded hydrogels, drug-loaded hydrogels, carbon-material-loaded hydrogels, hydrogels with fixed antimicrobial activity and biological antimicrobial hydrogels, and provides an outlook on the high antimicrobial activity, biodegradability, biocompatibility, injectability, clinical applicability and future development prospects of hydrogels in this field.

Review of NiS-Based Electrode Nanomaterials for Supercapacitors.

As a new type of energy storage device, supercapacitors have the advantages of high-power densities, high safety factors, and low maintenance costs, so they have attracted widespread attention among researchers. However, a major problem with supercapacitors is that their energy densities are not high enough, which limits their application. Therefore, it is crucial to expand the application scenarios of supercapacitors to increase their energy density as much as possible without diminishing their advantages. The classification and working principles of supercapacitors are introduced in this paper. The electrochemical properties of pure NiS materials, NiS composites with carbon materials, NiS composites with sulfide materials, and NiS composites with transition metal oxides for supercapacitors are summarized. This paper may assist in the design of new electrode materials for NiS-based supercapacitors.

Ruthenium-Alloyed Iron Phosphide Single Crystal with Increased Fermi Level for Efficient Hydrogen Evolution.

Transition metal phosphide alloying is an effective approach for optimizing the electronic structure and improving the intrinsic performance of the hydrogen evolution reaction (HER). However, obtaining 3d transition metal phosphides alloyed with noble metals is still a challenge owing to their difference in electronegativity, and the influence of their electronic structure modulated by noble metals on the HER reaction also remains unclear. In this study, we successfully incorporated Ru into an Fe2P single crystal via the Bridgeman method and used it as a model catalyst, which effectively promoted HER. Hall transport measurements combined with first-principles calculations revealed that Ru acted as an electron dopant in the structure and increased the Fermi level, leading to a decreased water dissociation barrier and an improved electron-transfer Volmer step at low overpotentials. Additionally, the (21̅1) facet of Ru-Fe2P was found to be more active than its (001) facet, mainly due to the lower H desorption barrier at high overpotentials. The synergistic effect of Ru and Fe sites was also revealed to facilitate H* and OH* desorption compared with Fe2P. Therefore, this study elucidates the boosting effect of Ru-alloyed iron phosphides and offers new understanding about the relationship between their electronic structure and HER performance.

Correlation of Circadian Rhythms of Heart Rate Variability Indices with Stress, Mood, and Sleep Status in Female Medical Workers with Night Shifts.

Purpose: Heart rate variability (HRV) indices have been used as stress indicators. Rare studies investigated the associations of circadian rhythms of the HRV indices with the stress, mood, and sleep conditions in populations under stress. Methods: In total 257 female participants (203 shift workers and 54 non-shift workers) were included. All the participants completed a structured questionnaire to assess the stress, mood, and sleep conditions and performed 24-hour Holter electrocardiogram monitoring on the day away from shifts. Using epochs of 1-min or 5-min beat-to-beat intervals, the HRV indices (SDNN, RMSSD, LF, HF, LF/HF, and LFnu, SD1, SD2, SD1/SD2) were plotted as a function of time and fitted into cosine periodic curves, respectively. Three mathematical parameters based on the cosine periodic curves were extracted, MESOR (M, overall averages of the cosine curve), amplitude (A, amplitude of the peak of the cosine curve), and acrophase (θ, latency to the peak) to quantify the circadian rhythms of the HRV indices. Multivariable linear regression models were used to reveal the associations of these parameters with the clinical assessments of stress, mood, or sleep conditions, as well as with the 24-h averages of the HRV indices. Results: The parameters M and A of SDNN, RMSSD, LF, and HF, and θ of LF/HF and LFnu significantly differ between shift and non-shift workers. The parameter θ of LF/HF positively correlates with the severity of stress and anxiety. The parameter A of LF/HF and LFnu also positively correlates with daytime sleepiness and sleep fragmentation. In addition, the parameters M and A instead of θ of SDNN, RMSSD, LF, LF/HF, and LFnu significantly correlate with the 24-h averages of HRV indices. Conclusion: The circadian rhythms of the HRV indices over 24 hours can, to some extent, predict the severity of stress, emotion and sleep conditions in female populations under stress.

Main-Group Catalysts with Atomically Dispersed In Sites for Highly Efficient Oxidative Dehydrogenation.

Transition metal oxides are well-known catalysts for oxidative dehydrogenation thanks to their excellent ability to activate alkanes. However, they suffer from an inferior alkene yield due to the trade-off between the conversion and selectivity induced by more reactive alkenes than alkanes, which obscures the optimization of catalysts. Herein, we attempt to overcome this challenge by activating a selective main-group indium oxide considered to be inactive for oxidative dehydrogenation in conventional wisdom. Atomically dispersed In sites with the local structure of [InOH]2+ anchored by substituting the protons of supercages in HY are enclosed to be active centers that enable the activation of ethane with a metal-normalized turnover number of almost one magnitude higher than those of their supported In2O3 counterparts. Furthermore, the structure of isolated [InOH]2+ sites could be stabilized by in situ formed H2O from the selective oxidation of hydrogen by In2O3 nanoparticles. As a result, the as-designed main-group In catalysts exhibit 80% ethene selectivity at 80% ethane conversion, thus achieving 60% ethene yield due to active isolated [InOH]2+ sites and selective In2O3 nanoparticles, outperforming state-of-the-art transition metal oxide catalysts. This study unlocks new opportunities for the utilization of main-group elements and could pave the way toward a more rational design of catalysts for highly efficient selective oxidation catalysis.

3,4,5-Trimethoxycinnamate thymol ester inhibits melanogenesis in normal human melanocytes and 3D human epidermal equivalents via the PGC-1α-independent PPARγ partial agonism.

BACKGROUND: 3,4,5-Trimethoxycinnamate thymol ester (TCTE), an anti-melanogenic cosmetic agent prescribed currently, promotes adiponectin synthesis during adipogenesis in human bone marrow mesenchymal stem cells (hBM-MSCs). Adiponectin inhibits melanin biosynthesis and its biosynthesis is directly regulated by peroxisome proliferator-activated receptor (PPAR) γ. In this regard, TCTE may potentially affect PPARγ activity. However, contradicting effects of PPARγ agonists with different chemical structures on human melanogenesis have been reported. OBJECTIVE: A molecular target of TCTE was investigated to elucidate the association of both adiponectin and PPARγ with anti-melanogenic activity. METHODS: The adiponectin secretion-promoting activity of TCTE was tested in an adipogenesis model of hBM-MSCs. A molecular target of TCTE for adiponectin secretion was evaluated via time-resolved fluorescence resonance energy transfer-based receptor binding and transactivation of PPARs. RESULTS: TCTE significantly promoted adiponectin secretion (EC50, 27.9 µM) during adipogenesis in hBM-MSCs and directly bound to PPARγ (Ki, 13.2 µM). The TCTE-bound PPARγ increased the recruitment of SRC-1, SRC-3, and TRAP220/DRIP-1 coactivator peptides without affecting PGC-1α coactivation. In the docking analysis, the optimal ligand binding mode of TCTE exhibited typical ligand-receptor interactions of PPARγ partial agonists. The PPARγ partial agonism of TCTE was established experimentally and the anti-melanogenic activity of TCTE was decreased by treatment with a PPARγ antagonist in cultured normal human melanocytes and a 3D model of human epidermis. CONCLUSION: The anti-melanogenic activity of TCTE was associated with a PGC-1α-independent PPARγ partial agonism.

Improving classification of the external branch of the superior laryngeal nerve with neural monitoring: a research appraisal and narrative review.

OBJECTIVE: To review the published literature on external branch of superior laryngeal nerve (EBSLN) neural monitoring and propose a new EBSLN classification system using intraoperative neural monitoring (IONM). BACKGROUND: The injury rate of the external branch of the superior laryngeal nerve (EBSLN) in thyroid surgery is 0-58%. Symptoms of EBSLN injury are not consistent, and patients often complain of modification of the voice timbre with the preservation of vocal cord function. Standards for the diagnosis of EBSLN injury are lacking. METHODS: The PubMed database was searched using the terms 'External branch of the superior laryngeal nerve' and 'Intraoperative neuromonitoring' from 2010 through March 2020. CONCLUSIONS: This paper reviewed the anatomy of the EBSLN, the diagnosis and treatment of injury, and the application of IONM in the EBSLN. The traditional EBSLN classification method was analyzed and compared with our new classification method. The diagnosis of EBSLN injury is a problem that still needs to be resolved. For anatomic classifications of the EBSLN, we found that the conventional classification systems may not accurately reflect the real status of the EBSLN and the surgical risks that may occur intraoperatively. Using IONM, we developed an EBSLN classification method that was consistent with conventional diagnosis and treatments and can be widely and easily utilized during surgery.

Near 100% ethene selectivity achieved by tailoring dual active sites to isolate dehydrogenation and oxidation.

Prohibiting deep oxidation remains a challenging task in oxidative dehydrogenation of light alkane since the targeted alkene is more reactive than parent substrate. Here we tailor dual active sites to isolate dehydrogenation and oxidation instead of homogeneously active sites responsible for these two steps leading to consecutive oxidation of alkene. The introduction of HY zeolite with acid sites, three-dimensional pore structure and supercages gives rise to Ni2+ Lewis acid sites (LAS) and NiO nanoclusters confined in framework wherein catalytic dehydrogenation of ethane occurs on Ni2+ LAS resulting in the formation of ethene and hydrogen while NiO nanoclusters with decreased oxygen reactivity are responsible for selective oxidation of hydrogen rather than over-oxidizing ethene. Such tailored strategy achieves near 100% ethene selectivity and constitutes a promising basis for highly selective oxidation catalysis beyond oxidative dehydrogenation of light alkane.

Proprieties of adhesive surface arrays to thyroid cartilage for recurrent laryngeal nerve monitoring.

BACKGROUND: To investigate the optimal placement and size of adhesive thyroid cartilage electrodes (ATCEs) placed on the thyroid cartilage in porcine models for evaluating recurrent laryngeal nerve function compared with the other 3 recording electrode types. METHODS: Four Meishan piglets were used for this study. The electromyogram (EMG) signal stability was detected by intraoperative nerve monitoring (IONM). Best location and size of ATCEs were detected, and the EMG signals from each were compared. Latency data were tested by stimulating the different nerve points, and 6 manipulations of the trachea and endotracheal tube (ET) were applied to test the stability of EMG signals. ET electrodes, needle electrodes, and transcutaneous recording electrodes were simultaneously tested with comparison to ATCEs. RESULTS: The optimal placement locations and sizes of ATCEs were determined. The amplitudes and latencies recorded from the ATCEs were consistent with those of the ET electrodes. More anti-interference was observed with the ATCEs than with the ET electrodes in surgical manipulations. ATCEs could be used during intermittent and continuous monitoring in similar fashion to ET electrodes and needle electrodes. CONCLUSIONS: ATCEs had consistent monitoring function with ET electrodes and needle electrodes. Feasibility, EMG stability, and optimal location and size of ATCEs for IONM were resolved. The EMG profiles from the ATCEs were more stable during surgical manipulations.

Diallyl Biphenyl-Type Neolignans Have a Pharmacophore of PPARα/γ Dual Modulators.

Adiponectin secretion-promoting compounds have therapeutic potentials in human metabolic diseases. Diallyl biphenyl-type neolignan compounds, magnolol, honokiol, and 4-O-methylhonokiol, from a Magnolia officinalis extract were screened as adiponectin- secretion promoting compounds in the adipogenic differentiation model of human bone marrow mesenchymal stem cells (hBM-MSCs). In a target identification study, magnolol, honokiol, and 4-O-methylhonokiol were elucidated as PPARα and PPARγ dual modulators. Diallyl biphenyl-type neolignans affected the transcription of lipid metabolism-associated genes in a different way compared to those of specific PPAR ligands. The diallyl biphenyl-type neolignan structure provides a novel pharmacophore of PPARα/γ dual modulators, which may have unique therapeutic potentials in diverse metabolic diseases.

Preparation of Porous Activated Carbons for High Performance Supercapacitors from Taixi Anthracite by Multi-Stage Activation.

Coal-based porous materials for supercapacitors were successfully prepared using Taixi anthracite (TXA) by multi-stage activation. The characterization and electrochemical tests of activated carbons (ACs) prepared in different stages demonstrated that the AC from the third-stage activation (ACIII) shows good porous structures and excellent electrochemical performances. ACIII exhibited a fine specific capacitance of 199 F g-1 at a current density of 1 A g-1 in the three-electrode system, with 6 mol L-1 KOH as the electrolyte. The specific capacitance of ACIII remained 190 F g-1 even despite increasing the current density to 5 A g-1, indicating a good rate of electrochemical performance. Moreover, its specific capacitance remained at 98.1% of the initial value after 5000 galvanostatic charge-discharge (GCD) cycle tests at a current density of 1 A g-1, suggesting that the ACIII has excellent cycle performance as electrode materials for supercapacitors. This study provides a promising approach for fabricating high performance electrode materials from high-rank coals, which could facilitate efficient and clean utilization of high-rank coals.

Kojyl cinnamate esters are peroxisome proliferator-activated receptor α/γ dual agonists.

Adiponectin is an adipocytokine with insulin-sensitizing, anti-inflammatory, anti-atherosclerotic, and anti-aging properties. Compounds with the ability to promote adiponectin secretion are of interest for the development of anti-aging drugs to improve skin-aging phenotypes. In the phenotypic assay to measure adiponectin secretion during adipogenesis in human adipose tissue-derived mesenchymal stem cells (hAT-MSCs), kojyl cinnamate ester derivatives increased adiponectin secretion. A target identification study showed that the kojyl cinnamate ester derivatives competitively bound to peroxisome proliferator-activated receptor α/γ (PPARα/γ). The upregulation of adiponectin production induced by kojyl cinnamate ester derivatives was significantly correlated with PPARα and PPARγ binding activities. Kojyl cinnamate ester derivatives significantly increased the transcription of genes encoding cholesterol and fatty acid synthesizing enzymes in hAT-MSCs. Notably, the kojyl cinnamate esters upregulated the gene transcription of lipid metabolic enzymes in human epidermal keratinocytes, which are important in the integrity of skin permeability barrier. In addition, the kojyl cinnamate esters that function as PPARα/γ dual modulators inhibited ultraviolet B irradiation-induced inflammation in human epidermal keratinocytes. Therefore, kojyl cinnamate ester derivatives are a novel class of PPARα/γ dual agonists with the potential to improve skin-aging phenotypes.

Tigecycline Susceptibility and Molecular Resistance Mechanisms Among Clinical Klebsiella pneumoniae Strains Isolated During Non-Tigecycline Treatment.

Tigecycline is one of the few therapeutic options that are available for treating serious clinical infections. However, tigecycline nonsusceptible Enterobacteriaceae has emerged recently in China. In this study, a total of 28 clinical Klebsiella pneumoniae isolates that were not previously exposed to tigecycline were collected and confirmed for tigecycline minimum inhibitory concentrations (MICs) using standard broth microdilution tests. To elucidate the mechanisms underlying molecular resistance to tigecycline, the expression levels of efflux pumps AcrAB and OqxAB and their regulators RamA, MarA, RarA, and SoxS were determined by quantitative polymerase chain reaction. The expression levels of the genes acrB, ramA, marA, and soxS were statistically different in different MIC groups (p < 0.05). Sequence analysis of the acrR and ramR genes revealed several nonsynonymous mutations in the nine resistance isolates. The values of MIC in these isolated strains with ramR mutations were significantly higher than those without ramR mutation (p = 0.029). Moreover, mutations in the ramR gene led to the overexpression of RamA. These results indicated that the mutation of the ramR gene through the upregulated expression of RamA contributed to tigecycline resistance and that several of the newly identified types of mutations in ramR and acrR were not previously reported in K. pneumoniae clinical isolates.

Emergence and characterization of tigecycline resistance in multidrug-resistant Klebsiella pneumoniae isolates from blood samples of patients in intensive care units in northern China.

Serious infections in intensive care unit patients caused by multidrug-resistant (MDR) Klebsiella pneumoniae represent a major threat worldwide owing to increased mortality and limited treatment options. With the application of tigecycline for MDR pathogens, tigecycline-non-susceptible K. pneumoniae isolates have recently emerged in China. To identify the susceptibility profile of MDR K. pneumoniae to tigecycline and evaluate the molecular characterization of tigecycline resistance, 214 MDR K. pneumoniae isolates were collected from blood samples of patients in intensive care units. MICs and clonal relatedness were determined by standard broth microdilution and multilocus sequence typing, respectively. Expression levels of efflux pumps and their global regulators were examined using real-time PCR. Mutations of local repressor were identified by PCR and sequencing. Our results show that the tigecycline resistance rate of 214 MDR K. pneumoniae isolates was 6.07 %. ST11 was the predominant clone type of tigecycline-non-susceptible K. pneumoniae isolates. Expression of efflux pump AcrB and global regulator RamA correlated with tigecycline MICs (AcrB: x2=8.91, P=0.03; RamA: x2=13.91, P<0.01), and mean expression levels of AcrB for the MICs ≥4 mg l-1 were significantly higher than MICs ≤2 mg l-1 (t=2.48, P=0.029). In addition, one tigecycline-resistant isolate harboured a deletion mutation in the ramR gene. These data indicated a linear correlative trend for overexpression of the AcrB and the tigecycline MICs resulting from the upregulation of RamA. The emergence of molecular type ST11 of MDR K. pneumoniae isolates should be monitored to identify factors that contribute to tigecycline resistance in intensive care units.