[Early recognition and prevention of systemic sclerosis].

Systemic sclerosis is a disease characterized by skin and internal organ fibrosis, lacking specific therapeutic drugs and having a poor prognosis. Early diagnosis and intervention of the disease is of significant value in improving patient prognosis. This article provides a systematic review of the early diagnosis and treatment of systemic sclerosis, including early symptom recognition, laboratory testing, and drug intervention. It will provide a reference for the prevention of this disease.

[Epidural photobiomodulation accelerates the drainage of brain interstitial fluid and its mechanism].

OBJECTIVE: To evaluate the effect of photobiomodulation (PBM) on the drainage of brain interstitial fluid (ISF) and to investigate the possible mechanism of the positive effect of PBM on Alzheimer's disease (AD). METHODS: Twenty-four SD male rats were randomly divided into PBM group (n=12), sham PBM group (n=6), and negative control group (n=6). According to the injection site of tracer, the PBM group was further divided into PBM-ipsilateral traced group (n=6) and PBM-contralateral traced group (n=6). Rats in the PBM group and the sham PBM group were exposed to the dura minimally invasively on the skull corresponding to the frontal cortical area reached by ISF drainage from caudate nucleus region. The PBM group was irradiated by using 630 nm red light (5-6 mW/cm2), following an irradiation of 5 min with a 2 min pause, and a total of 5 times; the sham PBM group was kept in the same position for the same time using the light without power. The negative control group was kept without any measure. After PBM, tracer was injected into caudate nucleus of each group. The changes of ISF drainage in caudate nucleus were observed according to the diffusion and distribution of tracer molecule by tracer-based magnetic resonance imaging, and the structural changes of brain extracellular space (ECS) were analyzed by diffusion rate in ECS-mapping (DECS-mapping) technique. Finally, parameters reflecting the structure of brain ECS and the drainage of ISF were obtained: volume fraction (α), tortuo-sity (λ), half-life (T1/2), and DECS. The differences of parameters among different groups were compared to analyze the effect of PBM on brain ECS and ISF. One-Way ANOVA post hoc tests and independent sample t test were used for statistical analysis. RESULTS: The parameters including T1/2, DECS, and λ were significantly different among the PBM-ipsilateral traced group, the PBM-contralateral traced group, and the sham PBM group (F=79.286, P < 0.001; F=13.458, P < 0.001; F=10.948, P=0.001), while there was no difference in the parameter α of brain ECS among the three groups (F=1.217, P=0.324). Compared with the sham PBM group and the PBM-contralateral traced group, the PBM-ipsilateral traced group had a significant decrease in the parameter T1/2 [(45.45±6.76) min vs. (76.01±3.44) min, P < 0.001; (45.45±6.76) min vs. (78.07±4.27) min, P < 0.001], representing a significant acceleration of ISF drainage; the PBM-ipsilateral traced group had a significant increase in the parameter DECS [(4.51±0.77)×10-4 mm2/s vs. (3.15±0.44)×10-4 mm2/s, P < 0.001; (4.51±0.77)×10-4 mm2/s vs. (3.01±0.38)×10-4 mm2/s, P < 0.001], representing a significantly increased molecular diffusion rate of in the brain ECS; the PBM-ipsilateral traced group had a significant decrease in the parameter λ (1.51±0.21 vs. 1.85±0.12, P=0.001; 1.51±0.21 vs. 1.89±0.11, P=0.001), representing a significant decrease in the degree of tortuosity in the brain ECS. CONCLUSION: PBM can regulate the brain ISF drainage actively, which may be one of the potential mechanisms of the effect of PBM therapy on AD. This study provides a new method for enhancing the brain function via ECS pathway.

Multidrug-resistant Gram-negative bacteria in solid organ transplant recipients with bacteremias.

Bloodstream infections (BSIs) remain as life-threatening complications and are associated with significant morbidity and mortality among solid organ transplant (SOT) recipients. Multidrug-resistant (MDR) Gram-negative bacteria can cause serious bacteremias in these recipients. Reviews have aimed to investigate MDR Gram-negative bacteremias; however, they were lacking in SOT recipients in the past. To better understand the characteristics of bacteremias due to MDR Gram-negative bacteria, optimize preventive and therapeutic strategies, and improve the outcomes of SOT recipients, this review summarize the epidemiology, clinical and laboratory characteristics, and explores the mechanisms, prevention, and treatment of MDR Gram-negative bacteria.

Frequency and clinical outcomes of ESKAPE bacteremia in solid organ transplantation and the risk factors for mortality.

BACKGROUND: Although bacteremias caused by the 6 ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) have recently been highlighted as a serious complication in solid organ transplant (SOT), more information is urgently needed. We sought to investigate the frequency and clinical outcomes of ESKAPE bacteremia in SOT and determine the risk factors for mortality. METHODS: A retrospective analysis of bacteremia after SOT was reviewed. Risk factors for mortality caused by ESKAPE bacteremia were identified. RESULTS: Eighty-four episodes of bacteremia were caused by ESKAPE strains. Of these strains, 41 were caused by resistant ESKAPE (rESKAPE) organisms. The only factor for bacteremia-related mortality independently associated with ESKAPE was septic shock (odds ratio [OR] = 21.017, 95% confidence interval [CI] = 5.038-87.682, P < 0.001). The factors for bacteremia-related mortality independently associated with rESKAPE bacteremia were septic shock (OR = 16.558, 95% CI = 6.620-104.668, P = 0.003) and age ≥40 years (OR = 7.521, 95% CI = 1.196-47.292, P = 0.031). CONCLUSIONS: To improve the outcomes of transplantation, more effective therapeutic treatments are of paramount importance when older SOT recipients with bacteremia due to ESKAPE/rESKAPE organisms present with septic shock.

Applications of Cryogenic Electron Microscopy in Biomineralization Research.

Biological mineralization is a natural process manifested by living organisms in which inorganic minerals crystallize under the scrupulous control of biomolecules, producing hierarchical organic-inorganic composite structures with physical properties and design that galvanize even the most ardent structural engineer and architect. Understanding the mechanisms that control the formation of biominerals is challenging in the biomimetic engineering of hard tissues. In this regard, the contribution of cryogenic electron microscopy (cryo-EM) has been nothing short of phenomenal. By preserving materials in their native hydrated status and reducing damage caused by ion beam radiation, cryo-EM outperforms conventional transmission electron microscopy in its ability to directly observe the morphologic evolution of mineral precursor phases at different stages of biomineralization with nanoscale spatial resolution and subsecond temporal resolution in 2 or 3 dimensions. In the present review, the development and applications of cryo-EM are discussed to support the use of this powerful technique in dental research. Because of the rapid development of cryogenic sample preparation techniques, direct electron detection, and image-processing algorithms, the last decade has witnessed an exponential increase in the use of cryo-EM in structural biology and materials research. By amalgamating with other analytic techniques, cryo-EM may be used for qualitative and quantitative analyses of the kinetics and thermodynamic mechanisms in which organic macromolecules participate in the transformation of mineral precursors from their original liquid state to amorphous and ultimately crystalline phases. The present review concentrates on the biomineralization of calcium phosphate mineral phases, while that of calcium carbonate, silica, and magnetite is only briefly mentioned. Bioinspired organic matrix-mediated inorganic crystallization strategies are discussed from the perspective of tissue regeneration engineering.

Attitude and Impact Factors Toward Organ Transplantation and Donation Among Transplantation Nurses in China.

BACKGROUND: Health workers' awareness and knowledge of transplantation medicine can improve people's sensitivity and reduce their degree of opposition to donations. The medical literature contains numerous examples of attitudes toward organ transplantation and donation aimed at university students or medical staff members, but rarely for transplantation nurses. OBJECTIVE: The purposes of the study were to investigate the attitudes toward organ transplantation and donation among transplantation nurses and to explore the impact factors. METHODS: The study was conducted in 37 transplantation surgery wards in 22 hospitals using cross-sectional approach. SPSS (International Business Machines Corporation, Armonk, New York, USA) 7.0 software was used to analysis descriptive and inferential statistics for data. RESULTS: Five hundred thirty-six effective questionnaires were received and the effective rate was 89.33%. Nurses' mean age was 28.40 years with a mean service length of 6.54 years. Among these nurses, 66.6% and 78.0% were willing to accept organ transplantation surgery for themselves and their relatives, respectively. Of these nurses, 33.4% would donate their organs after death; whereas 39.9% were uncertain. Only 38.2% were willing to register in the national organ donation system. Of these nurses, 28.2% were willing to sign the organ donation consent forms when their relatives became potential organ donors, and 45.7% were uncertain. Eight independent variables that affected nurses' attitudes toward donating their organs from most to least significant were: ratio of nurse to bed, title, employment form, age, length of service, position, monthly income, and the highest educational degree earned. Pearson correlation analysis showed a significant correlation among nurses' attitudes toward organ transplantation, organ donation, and online registration. CONCLUSION: The attitude toward donation and transplantation in the hospitals was not too optimistic, and an improvement in the training regarding transplantation and donation among nurses in China is necessary. Nurses are an important group who generate opinion in the patient population, and their negative attitudes can have a significant negative impact on society's attitudes toward organ donation.

Pseudomonas Aeruginosa Infection Among Liver Transplant Recipients: A Clinical Analysis of 15 Cases.

BACKGROUND: The aim of this study was to describe the incidence, time of onset, clinical characteristics, and outcomes of Pseudomonas aeruginosa infection after liver transplantation (LT) and to investigate the drug resistance of P aeruginosa to frequently used antibiotics to provide evidence for clinical prevention and therapy. METHODS: Patients undergoing LT from January 1, 2003, through June 30, 2015, were considered. We determined the site of infection and the drug susceptibility of P aeruginosa isolates and collected these patients' data to confirm post-LT clinical and laboratory characteristics. RESULTS: Of the 303 patients who underwent cadaveric LT, 15 (5.0%) developed 20 episodes of P aeruginosa infection. All episodes of P aeruginosa infection were early-onset, with the bloodstream being the most common source of infection. The majority (86.7%) of these recipients were in intensive care unit stay, and 7 (46.7%) patients had a body temperature of ≥38°C at the onset of infection and an inappropriate antibiotic therapy. In 14 (93.3%) patients, P aeruginosa infection was nosocomial infection. Platelet numbers of <50 × 10(9)/L and lymphocyte count of <300/mm(3) developed in 33.3% and 46.7% of patients, respectively. Seven (46.7%) deaths were attributable to P aeruginosa infection. Of these 20 P aeruginosa isolates, 10 (50%) each were carbapenem-resistant and multidrug-resistant. P aeruginosa was relatively susceptible to amikacin, levofloxacin, or cefoperazone-sulbactam (resistance rate, 30%). CONCLUSIONS: The bloodstream was the most common site of infection; a high body temperature, nosocomial origin, decreased platelet and lymphocyte count occurring in the early period after LT, high antibiotic resistance rate, and high morbidity and mortality rates were the main characteristics of P aeruginosa infection.

Bacteria Isolated From Respiratory Tract Specimens of Renal Recipients With Acute Respiratory Distress Syndrome Due to Pneumonia: Epidemiology and Susceptibility of the Strains.

OBJECTIVE: We estimated species distribution and frequency of antimicrobial resistance among bacterial pathogens isolated from respiratory tract specimens of renal recipients with acute respiratory distress syndrome (ARDS) due to pneumonia. METHODS: We retrospectively collected patient demographics and clinical characteristics and microbiologic culture data with the use of standard microbiologic procedures and commercially available tests. RESULTS: From January 2001 to August 2014, 320 respiratory tract specimens were obtained from 94 renal recipients with ARDS. Bacterial cultures were positive in 134 specimens from 68 recipients (72.3%), yielding 139 bacterial strains. The most commonly isolated species were gram-negative bacteria (111 isolates) with dominance of Acinetobacter baumanii (29.7%) and Pseudomonas aeruginosa (18.0%). The gram-negative bacteria were relatively resistant to 1st- and 2nd-generation cephalosporin and monocyclic beta-lactam and relatively sensitive to levofloxacin and meropenem, with rates of resistance of 80.2%, 76.6%, 73.9%, 36.0%, and 44.1%, respectively. The gram-positive bacteria, excluding Streptococcus uberis, were sensitive to glycopeptides and oxazolidone. CONCLUSIONS: Gram-negative bacteria predominated as 79.9% of isolates from respiratory tract specimens of renal recipients with ARDS. The gram-negative bacteria were relatively sensitive to levofloxacin and meropenem and the gram-positive bacteria were sensitive to glycopeptides and oxazolidone.

Mortality Predictors in Acute Respiratory Distress Syndrome Renal Transplant Recipients With ESKAPE/rESKAPE Pneumonia.

BACKGROUND: A sustained immunosuppressive state in renal transplant recipients is a factor that can contribute to increased incidence of acute respiratory distress syndrome (ARDS) due to pneumonia. ARDS renal recipients with ESKAPE (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter spp.) pneumonia are probably related to high morbidity and mortality. We therefore sought to investigate the frequency of ESKAPE and resistant ESKAPE (rESKAPE) pathogens isolated from respiratory tract specimens of renal recipients with ARDS and determine the risk factors for mortality. METHODS: A retrospective analysis of ARDS renal recipients with ESKAPE/rESKAPE pneumonia was reviewed. Multiple logistic regression analysis was conducted to identify the independent risk factors associated with infection-related mortality. RESULTS: During the study period, 88 ESKAPE pathogens obtained from respiratory tract specimens of 54 ARDS renal recipients were documented including 33 A. baumannii, 24 P. aeruginosa, 17 S. aureus, 6 K. pneumoniae, 8 Enterobacter species, and 0 E. Faecium. Among these ESKAPE organisms, 61.4% (54/88) were antimicrobial resistant. The risk factors for mortality independently associated with ARDS renal recipients with ESKAPE pneumonia were severe ARDS (odds ratio [OR] 4.3 (95% confidence interval [CI] 1.1-16.4), P = .032), serum creatinine level >1.5 mg/dL (OR 4.2 95% CI (1.0-17.9), P = .05) and body temperature less than 38°C (OR 5.0 (95% CI 1.3-19.6), P = .02) at ARDS onset. The independent determinants of mortality were associated with ARDS renal recipients with rESKAPE pneumonia were serum creatinine level >1.5 mg/dL (OR 13.7, 95% CI 1.3-142.1, P = .028) and body temperature less than 38°C (OR 5.5 (95% CI 1.1-26.6) at ARDS onset, P = .035). CONCLUSIONS: The majority of EPKAPE isolates were antimicrobial resistant. Mortality in ARDS renal recipients with ESKAPE/rESKAPE pneumonia was associated with the severity of ARDS, elevated serum creatinine level, or depressed febrile response at ARDS onset.

The Distribution, Drug Resistance, and Clinical Characteristics of Acinetobacter baumannii Infections in Solid Organ Transplant Recipients.

OBJECTIVE: Acinetobacter baumannii has become a major problem among solid organ transplant (SOT) recipients. The aim of this study was to investigate the distribution, drug resistance, and clinical characteristics of A baumannii infections in SOT recipients. METHODS: We retrospectively identified 78/1,850 (4.2%) SOT recipients who developed A baumannii infections from January 1, 2003, to April 1, 2015, and evaluated the distribution, drug resistance, and clinical characteristics of these infections. RESULTS: Over the study period, 101 episodes of A baumannii infection occurred in 78 SOT recipients, with respiratory tract (37.6%) and blood (35.6%) as the most common sites of infection. Fifty-six episodes of A baumannii infection were accompanied with a serum creatinine level of >1.5 mg/dL. Multidrug resistance (MDR) or extensive drug resistance (XDR) occurred in 83.2%. Antibiotic resistance rate of all A baumannii to 8 of 9 antibiotics investigated was >50%. Seventy-eight percent of A baumannii were carbapenem-resistant. All but one A baumannii isolates tested against polymyxin B were susceptible. There were 40 (51.3%) overall in-hospital deaths and 31 (39.7%) infection-related deaths. CONCLUSIONS: A baumannii infections are associated with high morbidity and mortality in SOT recipients, and MDR or XDR is common. Prevention measures are essential, and combination therapy of antibiotics are needed to improve the outcomes of SOT recipients with A baumannii infections.

Risk factors for mortality in liver transplant recipients with ESKAPE infection.

BACKGROUND: Although infections caused by the pathogens Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp (ESKAPE) have recently been identified as serious emerging problems in solid organ transplant, no information in liver transplant (LT) recipients is available. We sought to investigate the risk factors for associated mortality in LT recipients with ESKAPE infections. METHODS: A retrospective analysis of infection after LT was reviewed. Risk factors for mortality caused by ESKAPE infection were identified. RESULTS: Fifty-three episodes of infections caused by ESKAPE were documented in 51 LT recipients. The main sites of infection were the bloodstream (49.0%), the lungs (33.3%), and the intra-abdominal/biliary tract (17.6%). The risk factors for mortality independently associated with ESKAPE infection were female sex (odds ratio [OR] = 6.6, 95% confidence interval [CI] = 1.1-40.8, P = .042), septic shock (OR = 30.1, 95% CI = 3.7-244.8, P = .001), and lymphocyte counts <300/mm(3) (OR = 20.2, 95% CI = 2.9-142.2, P = .003). CONCLUSIONS: To improve the results of LT, more effective therapeutic treatments are of paramount importance when female LT recipients with ESKAPE infection present with septic shock and decreased lymphocyte counts.

Mannose-binding lectin 2 and ficolin-2 gene polymorphisms influence the susceptibility to bloodstream infections in kidney transplant recipients.

INTRODUCTION: Both mannose-binding lectin (MBL) and ficolin (FCN) interact with carbohydrate structures on microbial surfaces. Polymorphisms at the promoter and exon 1 of the MBL2 gene, which are responsible for low serum levels of MBL, have been shown to play important roles to increase the risk of post-transplant infections. Three gene polymorphisms in the promoter region of FCN2 and 2 in exon 8 (+6424 G > T) are associated with serum levels of FCN2 or binding capacity toward N-acetylglucosamine on microbial surfaces. METHODS: We prospectively analyzed 81 kidney transplant recipients for 6 well-known functional single-nucleotide polymorphisms in the MBL2 and 5 in the FCN2 gene of the recipients determined by gene sequencing. The bloodstream infections collected prospectively were associated with MBL2 and FCN2 genotypic variants over the first year after kidney transplantation. RESULTS: Multivariate analyses only found an association of recipient QQ + PQ genotypes of MBL2 5'-UTR +4 (odds ratio [OR] = 3.677, 95% confidence intervals [CI] = 1.127-11.998, P = .031) and FCN2 exon 8 Thr 236 Met(+6359 C > T) (OR = 4.917, 95% CI = 1.229-19.667, P = .024) with the incidence of bacteremia. CONCLUSION: Recipient QQ + PQ genotypes of MBL2 5'-UTR +4 and recipient FCN2 exon 8 Thr 236 Met(+6359 C > T) variants showed significant impacts on the risk of developing bloodstream infections after kidney transplantation.

Genetic association of tumor necrosis factor-ß, interleukin-10, and interleukin-1 gene cluster polymorphism with susceptibility to pneumonia in kidney transplant recipients.

INTRODUCTION: Pneumonia remains a significant cause of morbidity and mortality after kidney transplantation. The present study was therefore conducted to investigate whether or not the polymorphisms of tumor necrosis factor (TNF)ß, interleukin (IL)-10, IL-1ß, and IL-1 receptor antagonist (IL-1ra) gene predicted the susceptibility to pneumonia within the first year after kidney transplantation. METHODS: Subjects comprised 33 kidney transplant recipients with pneumonia and 63 noninfected kidney transplant recipients. Genomic DNA from these 96 kidney transplant recipients was extracted from peripheral blood leukocytes. The regions containing the NcoI polymorphic site at position +252 of TNFß gene, the RsaI polymorphic site at position -592 of IL-10 gene, and the AvaI polymorphic site at position -511 of IL-1ß gene were amplified by polymerase chain reaction (PCR) and subsequently digested with NcoI, RsaI, and AvaI restriction enzyme, respectively. The polymorphic regions with intron 2 of the IL-1 ra gene (IL-1 RN) containing variable numbers of a tandem repeat of 86 base pairs, were amplified by PCR. RESULTS: Univariate analysis showed that recipient IL-10, IL-1ß, and IL-1 RN polymorphisms were not associated with the presence of pneumonia (P = .589, .940, and .286, respectively). However, compared with GG genotype, recipient TNFß +252AA + AG genotype was significantly associated with susceptibility to pneumonia (P = .006). Age of 45 years or older was not significantly associated with susceptibility to develop pneumonia but had a tendency to develop it (P = .119). After adjusting for age of 45 years or older, recipient TNFß+252 AA + AG genotype (odds ratio = 5.366, 95% confidence intervals = 1.470 - 19.589, P = .011) independently predicted the risk for pneumonia within the first year after kidney transplantation in the multivariate analysis. CONCLUSION: These results suggested that recipient TNFß gene polymorphism may be useful in predicting pneumonia, hence identifying individuals who could benefit from preventive treatment and a less potent immunosuppression regimen.

The risk factors for mortality in deceased donor liver transplant recipients with bloodstream infections.

BACKGROUND: Information on risk factors for mortality among deceased donor liver transplant recipients with bloodstream infections (BSIs) was sought using a retrospective analysis from January 2002 to January 2012. METHODS: We performed deceased donor liver transplantations in 135 subjects who experienced 77 episodes of BSIs. We assessed risk factors for mortality among 43 of them using univariate and multivariate logistic regression analysis. RESULTS: The 43 recipients (31.9%) who developed BSI showed a mean age of 45.1 (45.1 ± 14.1 years). The majority of infections were nosocomial in origin (97.7%), with more than half being polymicrobial (53.5%). There were 24 deaths among these recipients (55.8%). The univariate analysis identified the following variables as risk factors for BSI-related mortality: polymicrobial (P = .029), platelet count <50,000/mm(3) (P = .02), creatinine > 1.5 mg/dL (P = .008), and septic shock (P < .001). Multivariate logistic regression showed the independent risk factors for mortality to be a serum creatinine > 1.5 mg/dL and septic shock. CONCLUSION: The risk factors significantly associated with increased mortality in deceased donor liver transplant recipients with BSIs are higher serum creatinine levels and septic shock. Despite appropriate antimicrobial treatment, BSIs accompanied by septic shock or higher serum creatinine levels were associated with high mortality rates. It is therefore essential to protect renal function to reduce the incidence of BSIs.

Genetic association of interleukin-1ß (-511C/T) and its receptor antagonist (86-bpVNTR) gene polymorphism with susceptibility to bacteremia in kidney transplant recipients.

BACKGROUND: Bacteremia remains a significant cause of morbidity and mortality after kidney transplantation. The present study was conducted to determine the influence of the polymorphisms of interleukin-1 ß (IL-1 ß) and IL-1 receptor antagonist gene (IL-1RN) on the susceptibility to bacteremia within the first year after kidney transplantation. METHODS: Twenty-one bacteremic and 60 noninfected kidney transplant recipients, underwent extraction genomic DNA, from peripheral blood leukocytes. The region containing the AvaI polymorphic site at position -511 of 1L-I ß gene was amplified by a polymerase chain reaction (PCR) and subsequently digested with AvaI restriction enzyme. The polymorphic regions within intron 2 of IL-1RN, containing variable numbers of a tandem repeat of 86 base pairs, were amplified by PCR. RESULTS: We observed greater frequency of the IL-1 ß -511CC genotype and IL-1 ß -511C allele among bacteremic versus noninfected recipients (P = .023 and P = .015, respectively). In contrast, the current study failed to show significant difference, either in genotypic or allelic frequency, for the IL-1RN polymorphisms regarding the incidence of bacteremia (P = .508 and P = .507, respectively). After adjustment we observed recipient IL-1 ß -511CC genotype (odds ratio [OR] = 4.400, 95% confidence interval [CI] = 1.517-12.759, P = .006) and recipient IL-1 ß-511C allele (OR = 2.444, 95% Cl = 1.172-5.100, P = .015) to predict independently the risk for bacteremia within the first year after kidney transplantation. CONCLUSION: The present work provided evidence that recipient IL-1 ß -511CC genotype or IL-1 ß -511C allele was associated with susceptibility to bacteremia within the first year after kidney transplantation. These results suggested that genotyping data may afford a more accurate prediction of bacteremia and the design of strategies to protect the most vulnerable patients.