Clinical manifestations and antimicrobial susceptibility of Nocardia species at a tertiary hospital in Taiwan, 2011-2020.

BACKGROUND: The study aimed to assess the clinical characteristics of patients with nocardiosis, to evaluate the in vitro susceptibility of antimicrobial agents against Nocardia species, and to explore changes in antimicrobial susceptibilities in this era of multidrug resistance. METHODS: Nocardia isolates were identified to the species level using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA, hsp65, and secA1 gene sequencing, and minimum inhibitory concentrations (MICs) of 15 antimicrobial agents were assessed with the broth microdilution method. RESULTS: Eighty-nine isolates from 68 patients were identified to species level. The most common species were Nocardia brasiliensis (n = 28, 31.5%), followed by N. farcinica (n = 24, 27%) and N. cyriacigeorgica (n = 16, 18%). Skin and soft tissue were the most common sites of nocardiosis. In multivariate analysis, cutaneous infection (OR, 0.052; p = 0.009), immunosuppressant use (OR, 16.006; p = 0.013) and Charlson combidity index (OR, 1.522; p = 0.029) were significant predictors for death. In total, 98.9% isolates were susceptible to trimethoprim-sulfamethoxazole and linezolid. Further, the MIC range and resistance rate of all Nocardia species to ceftriaxone, imipenem, and amoxicillin-clavulanic acid were found to generally increase over time. CONCLUSION: Considering that trimethoprim-sulfamethoxazole is effective against most Nocardia species, it is the antibiotic of choice in Taiwan. Besides, amikacin, tigecycline, and linezolid showed high activity against Nocardia species and are thus good alternatives or additional therapies to treat nocardiosis, depending on patient's underlying conditions and site of infection.

Antifungal susceptibility testing with YeastONE™ is not predictive of clinical outcomes of Cryptococcus neoformans var. grubii fungemia.

Mortality rates due to Cryptococcus neoformans var. grubii fungemia remain significant despite treatment with antifungal drugs. The predictive function of antifungal susceptibility and its correlation with treatment outcome remains controversial. A retrospective study was conducted from January 1, 2009, to December 31, 2016, on 85 patients with C. neoformans var. grubii fungemia confirmed by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Antifungal drug susceptibility was determined using the YeastONE™ colorimetric broth microdilution method coupled with Vizion™ System following the Clinical and Laboratory Standards Institute guidelines. Six antifungal agents-amphotericin B, fluconazole, flucytosine, itraconazole, posaconazole, and voriconazole-were tested. The patients' demographic data and clinical information were abstracted for further analyses. Antifungal regimens consisting of amphotericin B with or without fluconazole or flucytosine were administered for induction treatment of these patients, followed with intravenous or oral fluconazole for maintenance therapy. Clinical outcomes were defined by 14- and 30-day mortality rates. Risk factors associated with outcomes were fitted in a logistic regression model by univariate or multivariate method. Eighty-five patients with C. neoformans var. grubii fungemia were enrolled in the study. The Sequential Organ Failure Assessment Score, Glasgow Coma Scale, Charlson comorbidity score, and adequate duration of therapy for amphotericin B were predictors for mortality in univariate analysis. Antifungal susceptibility testing with YeastONE™ does not predict clinical outcomes of C. neoformans var. grubii fungemia. Greater disease severity, high comorbidities, poor consciousness level, and inappropriate treatment were associated with increased mortality in cryptococcemia cases.

Cryptococcus neoformans is an encapsulated yeast living in both plants and animals that is composed of three main serotypes: C. neoformans var. grubii, C. neoformans var. gattii, and C. neoformans var. neoformans. C. neoformans var. grubii is the most common disease-causing Cryptococcus species worldwide. C. neoformans var. gattii is more prevalent than C. neoformans var. neoformans in both tropical and subtropical regions of Asia. C. neoformans causes severe, even fatal, diseases such as pulmonary infection, bloodstream infection, skin and soft tissue infection, bone and joint infection, central nervous system infection, and disseminated infection, regardless of host immunocompetence. We conducted a retrospective study on 85 patients who contracted cryptococcemia from January 1, 2009, to December 31, 2016. This work conducted both microbiological and clinical studies involving in vitro susceptibility testing, demographic data, comorbidities, treatment modalities, and treatment outcomes. We utilized a modern medical technique-based instrument, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS; Biotyper, Bruker Daltonics, Inc.), which determines the unique proteomic fingerprint of an organism, to identify the C. neoformans serotype. We utilized Thermo Fisher Scientific™ Sensititre™ YeastONE™ colorimetric broth microdilution plates coupled with a Vizion™ Digital MIC Viewing System (a computer-assisted optical reading machine) to determine the in vitro susceptibility of amphotericin B, flucytosine, fluconazole, itraconazole, posaconazole, and voriconazole against 85 C. neoformans var. grubii blood isolates. In conclusion, the susceptibility patterns of these antifungal agents did not correlate significantly with treatment outcomes. However, a lower disease severity score, a lower Glasgow Coma Scale score, fewer comorbidities, and adequate amphotericin B treatment duration were predictors for treatment success in univariate analysis.

Epidemiology and outcomes of Endophthalmitis in chronic dialysis patients: a 13-year experience in a tertiary referral center in Taiwan.

BACKGROUND: Endophthalmitis is a severe eye infection leading to disabling outcome. Because there were only a few case report illustrating endophthalmitis in chronic dialysis patient, we would like to investigate the epidemiology and clinical features of endophthalmitis in chronic dialysis patient in a tertiary referral center. METHODS: We searched the health information system in the study hospital with ICD9 encoding endophthalmitis during Jan. 2002 to Dec. 2015. A total of 32 episodes of endophthalmitis occurred in chronic dialysis patients. We performed an 1:2 case-control match on propensity score. The demographic features, clinical manifestation, infection focus and visual outcome were recorded. RESULTS: Of the total of 32 patients, 25 were classified as endogenous endophthalmitis and another seven were exogenous. Most patients presented with ophthalmalgia (n = 32, 100%) and periocular swelling (n = 31, 96.8%), whereas half of the patients suffered blurred vision (n = 16, 50%). Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequent causative pathogens. Dialysis vascular infection was also a possible unique focus for bacteremia. The visual acuity of the endogenous groups were less likely to improve in the chronic dialysis patients compared with control group. CONCLUSION: This is the first and the largest case series focusing on endophthalmitis in chronic dialysis patients. Our study showed different pathogen spectrum, an unique bacterial origin and worse visual outcome in these group of patients. Prompt referral to ophthalmologists when the patients present with suspicious symptoms (blurred vision, ophthalmalgia and periocular swelling) is crucial.

Infective spondylodiscitis in patients on maintenance hemodialysis: a case series.

Infective spondylodiscitis is a rare disease. This case review describes the clinical course, risk factors, and outcomes of adult patients on maintenance hemodialysis who presented with infective spondylodiscitis at a single medical center in Taiwan. There were 18 cases (mean age: 64.9 ± 10.8 years) over more than 10 years. Analysis of underlying diseases indicated that 50% of patients had diabetes, 55.6% had hypertension, 55.6% had coronary artery disease, 22.2% had congestive heart failure, 22.2% had a cerebral vascular accident, 16.7% had liver cirrhosis, and 11.1% had malignancies. Sixty-one percent of patients had a degenerative spinal disease and the most common symptom was back pain (83.3%). A total of 38.9% of patients had leukocytosis, 99.4% had elevated levels of C-reactive protein, 78.6% had elevated erythrocyte sedimentation rates, and 55.6% had elevated levels of alkaline phosphatase. The average hemodialysis duration was 72.8 ± 87.5 months, and 8 patients (44.4%) started hemodialysis within 1 year prior to infective spondylodiscitis. Four patients (22.2%) had vascular access infection-associated spondylodiscitis. The lumbar region was the most common location of infection (77.8%), 44.4% of patients developed abscesses, and Staphylococci were the most common pathogen (38.9%). The mortality rate was 16.7%, all due to sepsis. Thirty-three percent of the survivors had recurrent infective spondylodiscitis within 1 year. Infective spondylodiscitis should be considered in hemodialysis patients who present with prolonged back pain with or without fever. Non-contrast MRI is an appropriate diagnostic tool for this condition. Vascular access infection increases the risk for infective spondylodiscitis in hemodialysis patients.

Developing a measure of medication-related quality of life for people with polypharmacy.

PURPOSE: To develop a measure of medication-related quality of life (MRQoL) and to validate the measure in a hospital-based population of patients with polypharmacy. METHODS: The Medication-Related Quality of Life Scale version 1.0 (MRQoLS-v1.0) included 14 items developed on the basis of interviews with elderly patients with polypharmacy, defined as taking five or more medications simultaneously. This scale was tested in 219 outpatients (99 with polypharmacy and 120 without polypharmacy). Two measures were used to establish construct validity the Psychological Distress Checklist, for convergent validity, and the Medication Adherence Behavior Scale (MABS), for discriminant validity. RESULTS: The 14-item scale was found to be both reliable and valid. Internal consistency reliability evaluated using Cronbach's alpha for this scale was 0.91. Scores on the MRQoLS-v1.0 correlated statistically significantly and negatively with those on the Psychological Distress Checklist. Discriminant validity was demonstrated by low correlation with MABS, indicating that the MRQoLS-v1.0 measured concepts different from medication adherence. Significant differences in the MRQoLS-v1.0 between patients with polypharmacy and those without polypharmacy provided evidence for known-group validity. CONCLUSIONS: The study presents a psychometric evaluation of a measure used to assess MRQoL of patients with polypharmacy. The instrument is practical to administer in clinics and provides a valuable adjunct to the outcome measurement for patients with polypharmacy. Further research on the sensitivity of this instrument to medication change in multi-medicated patients is warranted.

Low-Temperature Solution Synthesis of Few-Layer 1T '-MoTe2 Nanostructures Exhibiting Lattice Compression.

Molybdenum ditelluride, MoTe2 , is emerging as an important transition-metal dichalcogenide (TMD) material because of its favorable properties relative to other TMDs. The 1T ' polymorph of MoTe2 is particularly interesting because it is semimetallic with bands that overlap near the Fermi level, but semiconducting 2H-MoTe2 is more stable and therefore more accessible synthetically. Metastable 1T '-MoTe2 forms directly in solution at 300 °C as uniform colloidal nanostructures that consist of few-layer nanosheets, which appear to exhibit an approx. 1 % lateral lattice compression relative to the bulk analogue. Density functional theory calculations suggest that small grain sizes and polycrystallinity stabilize the 1T ' phase in the MoTe2 nanostructures and suppress its transformation back to the more stable 2H polymorph through grain boundary pinning. Raman spectra of the 1T '-MoTe2 nanostructures exhibit a laser energy dependence, which could be caused by electronic transitions.

Topological control of nitric oxide secretion by tantalum oxide nanodot arrays.

BACKGROUND: Nitric oxide (NO) plays a very important role in the cardiovascular system as a major secondary messenger in signaling pathway. Its concentration regulates most of the important physiological indexes including the systemic blood pressure, blood flow, regional vascular tone and other cardiac functions. The effect of nanotopography on the NO secretion in cardiomyocytes has not been elucidated before. In this study, we report how the nanotopography can modulate the secretion profile of NO and attempt to elucidate the genetic pathways responsible for the same by using Tantalum Oxide nanodot arrays ranging from 10 to 200 nm. A series of nanodot arrays were fabricated with dot diameter ranging from 10 to 200 nm. Temporal NO release of cardiomyocytes was quantified when grown on different surfaces. Quantitative RT-PCR and Western blot were performed to verify the genetic pathways of NO release. RESULTS: After hours 24 of cell seeding, NO release was slowly enhanced by the increase of dot diameter from 10 nm up to 50 nm, mildly enhanced to a medium level at 100 nm, and increase rapidly to a high level at 200 nm. The temporal enhancement of NO release dropped dramatically on day 3. On day 5, a topology-dependent profile was established that maximized at 50 nm and dropped to control level at 200 nm. The NO releasing profile was closely associated with the expression patterns of genes associated with Endothelial nitric oxide synthase (eNOS) pathway [GPCR, PI3K, Akt, Bad, Bcl-2, NFκB(p65), eNOS], but less associated with Inducible nitric oxide synthase (iNOS) pathway (TNF-α, ILK, Akt, IκBα, NFκB, iNOS). Western blotting of Akt, eNOS, iNOS, and NFκB further validated that eNOS pathway was modulated by nanotopology. CONCLUSIONS: Based on the findings of the present study, 50, 100 nm can serve as the suitable nanotopography patterns for cardiac implant surface design. These two nanodot arrays promote NO secretion and can also promote the vascular smooth muscle relaxation. The results of this study can improve the heart stent design in the medical treatments.

Gold nanoparticles regulate the blimp1/pax5 pathway and enhance antibody secretion in B-cells.

Nanoparticles are potential threats to human health and the environment; however, their medical applications as drug carriers targeting cancer cells bring hope to contemporary cancer therapy. As a model drug carrier, gold nanoparticles (GNPs) have been investigated extensively for in vivo toxicity. The effect of GNPs on the immune system, however, has rarely been examined. Antibody-secreting cells were treated with GNPs with diameters ranging from 2 to 50 nm. The GNPs enhanced IgG secretion in a size-dependent manner, with a peak of efficacy at 10 nm. The immune-stimulatory effect reached a maximum at 12 h after treatment but returned to control levels 24 h after treatment. This enhancing effect was validated ex vivo using B-cells isolated from mouse spleen. Evidence from RT-PCR and western blot experiments indicates that GNP-treatment upregulated B-lymphocyte-induced maturation protein 1 (blimp1) and downregulated paired box 5 (pax5). Immunostaining for blimp1 and pax5 in B-cells confirmed that the GNPs stimulated IgG secretion through the blimp1/pax5 pathway. The immunization of mice using peptide-conjugated GNPs indicated that the GNPs were capable of enhancing humoral immunity in a size-dependent manner. This effect was consistent with the bio-distribution of the GNPs in mouse spleen. In conclusion, in vitro, ex vivo, and in vivo evidence supports our hypothesis that GNPs enhance humoral immunity in mouse. The effect on the immune system should be taken into account if nanoparticles are used as carriers for drug delivery. In addition to their toxicity, the immune-stimulatory activity of nanoparticles could play an important role in human health and could have an environmental impact.

Digitizing abdominal palpation with a pressure measurement and positioning device.

An abdominal physical examination is one of the most important tools in evaluating patients with acute abdominal pain. We focused on palpation, in which assessment is made according to the patient's response and force feedback. Since palpation is performed manually by the examiner, the uniformity of force and location is difficult to achieve during examinations. We propose an integrated system to quantify palpation pressure and location. A force sensor continuously collects pressure data, while a camera locates the precise position of contact. The system recorded, displayed average and maximum pressure by creating a pressure/time curve for computer-aided diagnosis. Compared with previous work on pressure sensors of quantifying abdominal palpation, our proposed system is the integrated approach to measure palpation force and track the corresponding position at the same time, for further diagnosis. In addition, we only make use of a sensing device and a general web camera, rather than commercial algometry and infrared cameras used in the previous work. Based on our clinical trials, the statistics of palpation pressure values and the corresponding findings are also reported. We performed abdominal palpation with our system for twenty-three healthy participants, including fourteen males and nine females. We applied two grades of force on the abdomen (light and deep) by four-quadrant and nine-region schemes, record the value of pressure and location. In the four-quadrant scheme, the average pressures of abdominal palpation with light and deep force levels were 0.506(N) and 0.552(N), respectively. In the nine-region scheme, the average pressures were 0.496(N) and 0.577(N), respectively. Two episodes of contact dermal reaction were identified. According to our experiment statistics, there is no significant difference in the force level between the four-quadrant and nine-region scheme. Our results have the potential to be used as a reference guide while designing digital abdominal palpation devices.

Anti-hypertensive effects of Radix Rehmanniae and its active ingredients.

Radix Rehmanniae (RR) is the root tuber of Rehmannia glutinosa Libosch. Herein, the methanol extracts of dried RR (DRR) and processed RR (PRR) were partitioned to obtain ethyl acetate, aqueous, and n-butanol layers. The angiotensin-I converting enzyme (ACE) inhibition test indicated that the ethyl acetate extracts of DRR (DRRE) and PRR (PRRE) show better inhibitory activity. Therefore, changes in blood pressure were tested over 24 h in spontaneously hypertensive rats, with DRR showing good anti-hypertensive activity. DRRE was further subjected to column chromatography; 28 fractions were separated and tested for ACE inhibition. Ultimately, six compounds were identified by spectral analysis, and literature comparison. Specifically, ursolic acid and oleanolic acid showed better ACE inhibition than the other compounds. This study confirmed that DRR has anti-hypertensive activity. In future, DRR's potential as a health food should be further assessed.

Optimizing mass casualty burns intensive care organization and treatment using evidence-based outcome predictors.

BACKGROUND: Majority of current research focuses on pre-hospital care in mass casualty incidents (MCI) whereas this study is the first to examine multifactorial aspects of intensive care unit (ICU) resource management during a surge in massive burn injury (MBI) patients whilst identifying key outcome predictors that resulted in successful disaster managements. METHODS: Both critical care, surgical parameters and cost-effectiveness are investigated in patients admitted with severe burns resulting from the explosion. A fully integrated trauma response and expansion of critical care resources in Linkou Chang Gung Memorial Hospital (CGMH) in this incident is analyzed. RESULTS: 52 burn patients were treated in CGMH and 27 patients (51.9%) had TBSA greater than 45% with the mean TBSA of 44.6±20.3%. ICU based management of MBI including early debridement and resource strategizing. The overall mortality rate was 2/52 (3.85%). Patients had an average of 14.8days on mechanical ventilation and 43days as an inpatient in total. Operative treatment wise, 44.2% of patients received escharotomies and each patient received an average of 2 skin grafting procedures. The initial TBSA was a significant predictor for burn wound infection (OR 1.107, 95% CI 1.023-1.298; p=0.011). Each patient cost an average of USD 1035 per TBSA% with an average total cost of USD 50415. CONCLUSION: With ever increasing chances of terrorist activity in urban areas, hospitals can hopefully increase their preparedness using outcome-predictors presented in this study.

Epidemiology and Outcomes of Infectious Spondylodiscitis in Hemodialysis Patients.

STUDY DESIGN: A retrospective study of patients who were hospitalized for infectious spondylodiscitis over a 13-year period. OBJECTIVE: To elucidate the epidemiology and prognostic factors of infectious spondylodiscitis in hemodialysis (HD) patients and to identify the impact of HD on infectious spondylodiscitis. SUMMARY OF BACKGROUND DATA: Only a few case studies of infectious spondylodiscitis in HD patients can be found in the literature. Reports of prognostic factors are limited and patients' outcomes have not been well described. METHODS: The cases of 1402 patients who were hospitalized for infectious spondylodiscitis over a 13-year period were retrospectively reviewed. Of these, 102 patients on maintenance HD were enrolled in this study. Cox proportional hazard model was used to evaluate the risk factors of mortality and recurrence. RESULTS: The 102 enrolled patients had an average age 63.3 ±â€Š11.2 years old and male-to-female ratio of 1:1.04. Back pain was present in 75.5% of patients and the most commonly infected site was the lumbosacral spine. Infection associated with vascular access was identified in 31.4% of patients. The prevalence of dialysis via central venous catheters was higher than prevalent HD patients. Methicillin-resistant Staphylococcus aureus was the most common pathogen, followed coagulase-negative staphylococci. The patients' in-hospital survival rate was 82.4%; their vascular access survival rate was 75.5%; their 1-year survival rate was 78.4%, and their 1-year recurrence rate was 20.2%. Congestive heart failure was associated with an increased 1-year mortality. Other variables exhibited no significant relationship with patients' in-hospital mortality, 1-year mortality or recurrence. CONCLUSION: The characteristics and outcomes of infectious spondylodiscitis in HD patients were elucidated. Most of the demographic and clinical variables, evaluated upon admission, did not predict mortality or recurrence. LEVEL OF EVIDENCE: 3.

Extra nuchal-type fibroma associated with repetitive blunt trauma during religious activities.

Nuchal-type fibroma (NTF) is a rare, benign subcutaneous tumor that usually arises from the posterior neck. NTF is histologically characterised by dense collagen bundles and sparse fibroblasts. Only four trauma-related cases have been previously published. Herein, we present a case of extra NTF with histopathology, and six palanquin porters by using snowball sampling technique in ethnographic field research. A palanquin is a type of human-powered transport carried upon the shoulders mostly seen in religious processions. All individuals (mean age, 26.8 years) displayed similar shoulder masses measuring up to 12 cm in the greatest dimensions. They averaged approximately 8.1 years of palanquin-carrying work each. We believe that long-term, heavy shoulder weight bearing of palanquins in religious dance performances may attribute to the incidence of extra NTF. This study reviews all literature of trauma-associated NTF through PubMed database, and highlights the association between repetitive blunt trauma and the development of NTF.

Spatial Control of Cell-Nanosurface Interactions by Tantalum Oxide Nanodots for Improved Implant Geometry.

Nanotopological cues can be exploited to understand the nature of interactions between cells and their microenvironment to generate superior implant geometries. Nanosurface parameters which modulate the cell behavior and characteristics such as focal adhesions, cell morphology are not clearly understood. Here, we studied the role of different nanotopographic dimensions in modulating the cell behavior, characteristics and ultimately the cell fate and accordingly, a methodology to improve implant surface geometry is proposed. Tantalum oxide nanodots of 50, 100nm dot diameter with an inter-dot spacing of 20, 70nm and heights 40, 100nm respectively, were engineered on Silicon substrates. MG63 cells were cultured for 72 hours and the modulation in morphology, focal adhesions, cell extensible area, cell viability, transcription factors and genes responsible for bone protein secretion as a function of the nanodot diameter, inter-dot distance and nanodot height were evaluated. Nanodots of 50nm diameter with a 20nm inter-dot spacing and 40nm height enhanced cell spreading area by 40%, promoted cell viability by 70% and upregulated transcription factors and genes twice as much, as compared to the 100nm nanodots with 70nm inter-dot spacing and 100nm height. Favorable interactions between cells and all dimensions of 50nm nanodot diameter were observed, determined with Scanning electron microscopy and Immunofluorescence staining. Nanodot height played a vital role in controlling the cell fate. Dimensions of nanodot features which triggered a transition in cell characteristics or behavior was also defined through statistical analysis. The findings of this study provide insights in the parameters of nanotopographic features which can vitally control the cell fate and should therefore be taken into account when designing implant geometries.

Tungsten Ditelluride: a layered semimetal.

Tungsten ditelluride (WTe2) is a transition metal dichalcogenide (TMD) with physical and electronic properties that make it attractive for a variety of electronic applications. Although WTe2 has been studied for decades, its structure and electronic properties have only recently been correctly described. We experimentally and theoretically investigate the structure, dynamics and electronic properties of WTe2, and verify that WTe2 has its minimum energy configuration in a distorted 1T structure (Td structure), which results in metallic-like transport. Our findings unambiguously confirm the metallic nature of WTe2, introduce new information about the Raman modes of Td-WTe2, and demonstrate that Td-WTe2 is readily oxidized via environmental exposure. Finally, these findings confirm that, in its thermodynamically favored Td form, the utilization of WTe2 in electronic device architectures such as field effect transistors may need to be reevaluated.

Topographical control of cell-cell interaction in C6 glioma by nanodot arrays.

Nanotopography modulates the physiological behavior of cells and cell-cell interactions, but the manner of communication remains unclear. Cell networking (syncytium) of astroglia provides the optimal microenvironment for communication of the nervous system. C6 glioma cells were seeded on nanodot arrays with dot diameters ranging from 10 to 200 nm. Cell viability, morphology, cytoskeleton, and adhesion showed optimal cell growth on 50-nm nanodots if sufficient incubation was allowed. In particular, the astrocytic syncytium level maximized at 50 nm. The gap junction protein Cx43 showed size-dependent and time-dependent transport from the nucleus to the cell membrane. The transport efficiency was greatly enhanced by incubation on 50-nm nanodots. In summary, nanotopography is capable of modulating cell behavior and influencing the cell-cell interactions of astrocytes. By fine-tuning the nanoenvironment, it may be possible to regulate cell-cell communications and optimize the biocompatibility of neural implants.

Direct synthesis of van der Waals solids.

The stacking of two-dimensional layered materials, such as semiconducting transition metal dichalcogenides (TMDs), insulating hexagonal boron nitride (hBN), and semimetallic graphene, has been theorized to produce tunable electronic and optoelectronic properties. Here we demonstrate the direct growth of MoS2, WSe2, and hBN on epitaxial graphene to form large-area van der Waals heterostructures. We reveal that the properties of the underlying graphene dictate properties of the heterostructures, where strain, wrinkling, and defects on the surface of graphene act as nucleation centers for lateral growth of the overlayer. Additionally, we show that the direct synthesis of TMDs on epitaxial graphene exhibits atomically sharp interfaces. Finally, we demonstrate that direct growth of MoS2 on epitaxial graphene can lead to a 10(3) improvement in photoresponse compared to MoS2 alone.

DNA sequencing using electrical conductance measurements of a DNA polymerase.

The development of personalized medicine-in which medical treatment is customized to an individual on the basis of genetic information-requires techniques that can sequence DNA quickly and cheaply. Single-molecule sequencing technologies, such as nanopores, can potentially be used to sequence long strands of DNA without labels or amplification, but a viable technique has yet to be established. Here, we show that single DNA molecules can be sequenced by monitoring the electrical conductance of a phi29 DNA polymerase as it incorporates unlabelled nucleotides into a template strand of DNA. The conductance of the polymerase is measured by attaching it to a protein transistor that consists of an antibody molecule (immunoglobulin G) bound to two gold nanoparticles, which are in turn connected to source and drain electrodes. The electrical conductance of the DNA polymerase exhibits well-separated plateaux that are ~3 pA in height. Each plateau corresponds to an individual base and is formed at a rate of ~22 nucleotides per second. Additional spikes appear on top of the plateaux and can be used to discriminate between the four different nucleotides. We also show that the sequencing platform works with a variety of DNA polymerases and can sequence difficult templates such as homopolymers.

The spatial and temporal control of cell migration by nanoporous surfaces through the regulation of ERK and integrins in fibroblasts.

Nanotopography controls cell behaviours, such as cell adhesion and migration. However, the mechanisms responsible for topology-mediated cellular functions are not fully understood. A variety of nanopores was fabricated on 316L stainless steel to investigate the effects of spatial control on the growth and function of fibroblasts, the temporal regulation of integrins, and their effects on migration. The NIH-3T3 fibroblast cell line was cultured on the nanopore surfaces, whose pore diameters ranged from 40 to 210 nm. The 40 and 75 nm nanopores enhanced cell proliferation, focal adhesion formation and protein expression of vinculin and ß-tubulin after 24 h of incubation. Integrin expression was analysed by qPCR, which showed the extent of spatial and temporal regulation achieved by the nanopores. The protein expression of pERK1/2 was greatly attenuated in cells grown on 185 and 210 nm nanopore surfaces at 12 and 24 h. In summary, the 40 and 75 nm nanopore surfaces promoted cell adhesion and migration in fibroblasts by controlling the temporal expression of integrins and ERK1/2. The current study provides insight into the improvement of the design of stainless steel implants and parameters that affect biocompatibility. The ability to regulate the expression of integrin and ERK1/2 using nanopore surfaces could lead to further applications of surface modification in the fields of biomaterials science and tissue engineering.

Dosage-dependent induction of behavioral decline in Caenorhabditis elegans by long-term treatment of static magnetic fields.

The aim of this work was to explore the molecular mechanisms associated with possible health hazards induced by static magnetic fields (SMFs). Nematodes were grown under SMFs at field strengths from 0 to 200 mT, and the speed of body movement was measured. The effects of exposure to static magnetic fields were observed to be significant in the higher field strength and longer treatment. To explore the possible molecular mechanisms responsible for these effects, semi-quantitative real-time RT-PCR was performed using primers specific to 120 randomly selected genes. Twenty-six differentially expressed genes among apoptosis-, oxidative stress-, and cancer-related genes were identified, indicating that a global molecular response to SMF treatment occurred. The induction of apoptosis was verified by the increase of fluorescence in a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, by the caspase-3 activity assay, and by immunostaining using an antibody against the ced-3 gene product. Mutations in genes involved in major apoptotic pathways, that is, ced-3, ced-4, and ced-9, abolished this SMF-induced behavioral decline; this is consistent with the hypothesis that the apoptosis pathways are involved in the SMF-induced mobility decline. Here we show that long-term and low-dosage exposure to SMF is capable of inducing an apoptosis-mediated behavioral decline in nematodes.