Sub-diffraction optical beam lithography based on a center-non-zero depletion laser.

Photoinhibition (PI) mechanisms have been introduced in nanofabrication which allows breaking the diffraction limit by large factors. Donut-shaped laser is usually selected as a depletion beam to reduce linewidth, but the parasitic process has made the results of the experiment less than expected. As a result, the linewidth is difficult to achieve below 50 nm with 780 nm femtosecond and 532 nm continuous-wave lasers. Here, we propose a new, to the best of our knowledge, method based on a center-non-zero (CNZ) depletion laser to further reduce linewidth. By constructing a smaller zone of action under the condition of keeping the maximum depletion intensity constant, a minimum linewidth of 30 nm (λ / 26) was achieved. Two ways to construct CNZ spots were discussed and experimented, and the results show the advantages of our method to reduce the parasitic process to further improve the writing resolution.

Polysaccharide-based gold nanomaterials: Synthesis mechanism, polysaccharide structure-effect, and anticancer activity.

Polysaccharide-based gold nanomaterials have attracted great interest in biomedical fields such as cancer therapy and immunomodulation due to their prolonged residence time in vivo and enhanced immune response. This review aims to provide an up-to-date and comprehensive summary of polysaccharide-based Au NMs synthesis, including mechanisms, polysaccharide structure-effects, and anticancer activity. Firstly, research progress on the synthesis mechanism of polysaccharide-based Au NMs was addressed, which included three types based on the variety of polysaccharides and reaction environment: breaking of glycosidic bonds via Au (III) or base-mediated production of highly reduced intermediates, reduction of free hydroxyl groups in polysaccharide molecules, and reduction of free amino groups in polysaccharide molecules. Then, the potential effects of polysaccharide structure characteristics (molecular weight, composition of monosaccharides, functional groups, glycosidic bonds, and chain conformation) and reaction conditions (the reaction temperature, reaction time, pH, concentration of gold precursor and polysaccharides) on the size and shape of Au NMs were explored. Finally, the current status of polysaccharide-based Au NMs cancer therapy was summarized before reaching our conclusions and perspectives.

Parallel two-photon lithography achieving uniform sub-200†nm features with thousands of individually controlled foci.

The limited throughput of nano-scale laser lithography has been the bottleneck for its industrial applications. Although using multiple laser foci to parallelize the lithography process is an effective and straightforward strategy to improve rate, most conventional multi-focus methods are plagued by non-uniform laser intensity distribution due to the lack of individual control for each focus, which greatly hinders the nano-scale precision. In this paper, we present a highly uniform parallel two-photon lithography method based on a digital mirror device (DMD) and microlens array (MLA), which allows the generation of thousands of femtosecond (fs) laser foci with individual on-off switching and intensity-tuning capability. In the experiments, we generated a 1,600-laser focus array for parallel fabrication. Notably, the intensity uniformity of the focus array reached 97.7%, where the intensity-tuning precision for each focus reached 0.83%. A uniform dot array structure was fabricated to demonstrate parallel fabrication of sub-diffraction limit features, i.e., below 1/4 λ or 200 nm. The multi-focus lithography method has the potential of realizing rapid fabrication of sub-diffraction, arbitrarily complex, and large-scale 3D structures with three orders of magnitude higher fabrication rate.

Histopathological Study on Collagen in Full-Thickness Wound Healing in Fraser's Dolphins (Lagenodelphis hosei).

Fraser's dolphins (Lagenodelphis hosei) possess great healing abilities. Their skin composition can be restored after wounding, including collagen spacing, orientation, and bundle thickness. However, it remains unclear how collagens are involved in the wound-healing process and eventually regain normality in Fraser's dolphins. Learned from the other two scarless healing animals, changes in type III/I collagen composition are believed to modulate the wound healing process and influence the scarring or scarless fate determination in human fetal skin and spiny mouse skin. In the current study, Herovici's, trichrome, and immunofluorescence staining were used on normal and wounded skin samples in Fraser's dolphins. The results suggested that type I collagens were the main type of collagens in the normal skin of Fraser's dolphins, while type III collagens were barely seen. During the wound healing process, type III collagens showed at early wound healing stages, and type I collagen increased in the mature healed wound. In an early healed wound, collagens were organized in a parallel manner, showing a transient hypertrophic-like scar, and eventually restored to normal collagen configuration and adipocyte distribution in the mature healed wound. The remarkable ability to remove excessive collagens merits further investigation to provide new insights into clinical wound management.

Fabrication of Chiral 3D Microstructure Using Tightly Focused Multiramp Helico-Conical Optical Beams.

Beams with optical vortices are widely used in various fields, including optical communication, optical manipulation and trapping, and, especially in recent years, in the processing of nanoscale structures. However, circular vortex beams are difficult to use for the processing of chiral micro and nanostructures. This paper introduces a multiramp helical-conical beam that can produce a three-dimensional spiral light field in a tightly focused system. Using this spiral light beam and the two-photon direct writing technique, micro-nano structures with chiral characteristics in space can be directly written under a single exposure. The fabrication efficiency is more than 20 times higher than the conventional point-by-point writing strategy. The tightly focused properties of the light field were utilized to analyze the field-dependent properties of the micro-nano structure, such as the number of multiramp mixed screw-edge dislocations. Our results enrich the means of two-photon polymerization technology and provide a simple and stable way for the micromachining of chiral microstructures, which may have a wide range of applications in optical tweezers, optical communications, and metasurfaces.

Successful Repigmentation of Full-Thickness Wound Healing in Fraser's Dolphins (Lagenodelphis hosei).

Fraser's dolphins (Lagenodelphis hosei) exhibit the capability to restore nearly normal pigmentation after full-thickness wounding. However, the association among melanocytes, melanin and skin pigmentation during wound healing in cetaceans has yet to be addressed. Here, the number of melanocytes and the distribution of melanocytes and melanin in different-colored skin and different wound-healing stages in Fraser's dolphins were analyzed by using Fontana-Masson staining, immunofluorescence staining and immunohistochemical staining. It was noticed that there was the highest number of melanocytes in dark skin and the lowest number of melanocytes in white skin. The appearance of functional melanocytes and full-melanized neoepidermis was observed in the early stage of wound healing in Fraser's dolphins. Furthermore, the melanocyte number and skin pigmentation and pattern in healed wounds recovered to a similar condition of unwounded skin. This study provides fundamental knowledge of skin repigmentation in cetaceans for further research, and it will be warranted to elucidate the mechanisms of the replenishment of melanocytes and the regulation of melanocyte activity that contribute to the successful repigmentation in cetacean skin wounds.

Defining Wound Healing Progression in Cetacean Skin: Characteristics of Full-Thickness Wound Healing in Fraser's Dolphins (Lagenodelphis hosei).

Cetaceans are tight-skinned mammals that exhibit an extraordinary capacity to heal deep soft tissue injuries. However, essential information of large full-thickness wound healing in cetaceans is still lacking. Here, the stages of full-thickness wound healing were characterized in Fraser's dolphins (Lagenodelphis hosei). The skin samples were collected from normal skin and full-thickness cookiecutter shark (Isistius brasiliensis)-bite wounds of stranded carcasses. We defined five stages of wound healing according to macroscopic and histopathological examinations. Wounds in Stage 1 and 2 were characterized by intercellular and intracellular edema in the epidermal cells near the wound edge, mixed inflammatory cell infiltration, and degradation of collagen fibers. In Stage 3 wounds, melanocytes, melanin granules, rete and dermal ridges were noticed in the neo-epidermis, and the adipose tissue in adjacent blubber was replaced by cells and fibers. Wounds in Stage 4 and 5 were characterized by gradual restoration of the normal skin architecture including rete and dermal ridges, collagen bundles, and adipose tissue. These phenomena were quite different from previous studies in terrestrial tight-skinned mammals, and therefore, further in-depth research into the mechanisms of dolphin wound healing would be needed to gain new insights into veterinary and human regenerative medicine.

Theoretical analysis of thermal-lensing effect in a high power exciplex pumped Cs vapor laser.

Considering the kinetic and fluid dynamic processes in the gain medium, a theoretical model is established to describe the mechanism of thermal-lensing effect in an exciplex pumped Cs vapor laser. The three-dimensional distribution of temperature and index of refraction in the gain medium are depicted. The effective focal length and radius of thermal lens are predicted. Our simulation results show the thermal lens plays a non-negligible role in high-power XPCsLs and can be significantly aggravated in higher wall temperature, buffer pressure and pump intensity. The divergence of laser beam influenced by thermal lens is also made in detail. This model is helpful for in-depth understanding of the thermal-lensing effect in XPALs.

Fusarium solani species complex infection in elasmobranchs: A case report for rough-tail stingray with valid antifungal therapy.

Fusarium species are common plant and animal pathogens. For humans, there are two dominant species complexes, F. solani species complex (FSSC) and F. oxysporum species complex (FOSC), which both infect immunocompromised individuals. However, there are few reports related to elasmobranchs infected by Fusarium species. In this study, we report a case of a rough-tail stingray from an ocean park infected by FSSC diagnosed using histopathology and microscopic observation, with morphological characteristics and molecular techniques used to identify the pathogen. Histopathology showed fungal hyphae invading stingray tissues, while micro/macroconidia were found under the microscope. We identified this pathogen as FSSC 12 through phylogenetic analysis using internal transcribed spacer (ITS) and elongation factor 1-alpha (EF1-α) sequences. Furthermore, we report that application of voriconazole (orally) and terbinafine (topically) constituted an effective therapy, curing the stingray.

Numerical simulations on a nanosecond-pulse exciplex pumped cesium vapor laser.

A theoretical model is established to describe the kinetic processes and laser mechanism for a nanosecond-pulse exciplex pumped Cs vapor laser (XPCsL). A new simulation method is proposed to solve a set of non-stationary rate equations considering high energy levels and the results of simulation are consistent with the experimental data. The effects of cell temperature, pump energy and buffer gas on the output laser pulses are presented and analyzed in detail, which reveal the unique properties of nanosecond-pulse XPCsL.

Theoretical simulation on exciplex pumped Rb vapor laser.

Considering spectrally resolved absorption and temperature distribution, a physical model is established to describe the laser kinetic and thermodynamic processes of an exciplex pumped Rb vapor laser. A comparison with Carroll's model is made. Influences of pump intensity, temperature, reflectivity of output coupler, and number density of Kr on the performance of CW Rb-Kr XPAL with uniform temperature distribution are calculated and analyzed. Besides, with the heat accumulation considered, the temperature distribution was calculated, and the maximal optical-to-optical efficiency about 5.7% can be achieved at the condition of pump intensity I0 = 5.2 × 1010 W/m2 and flow velocity u = 250 m/s.

Locally extensive meningoencephalitis caused by Miamiensis avidus (syn. Philasterides dicentrarchi) in a zebra shark.

Scuticociliatosis, caused by ciliated protozoa in the subclass Scuticociliatia of the phylum Ciliophora, can cause fatal disease in teleost fish species. However, information on scuticociliatosis in elasmobranchs is still scarce. In this report, we describe a case of locally extensive meningoencephalitis caused by Miamiensis avidus (syn. Philasterides dicentrarchi) in a 2 yr old captive zebra shark Stegostoma fasciatum. Granulocytic meningoencephalitis was observed through histological assessment. Inflammation was confined to the ventral aspect of the brain with a large number of ciliated protozoa, transforming into non-suppurative meningitis in the lateral aspect, and gradually vanished in the dorsal aspect. No histopathological and polymerase chain reaction (PCR) evidence of systemic dissemination of M. avidus was found. PCR targeting the gene coding the small-subunit ribosomal RNA (SSUrRNA) of M. avidus was performed on the brain, liver, and gill tissues, and only brain tissue yielded a positive result. The DNA sequences from amplicons of the protozoal SSUrRNA gene were completely matched to that of M. avidus. The distribution of protozoa in the current case was mainly located in the brain and suggests the possibility of a direct neural invasive pathway of M. avidus through the nasal cavity/ampullary system and/or a unique tissue tropism of M. avidus specific to the brain in zebra sharks. Further investigations on the pathogenesis of M. avidus in elasmobranchs, especially zebra sharks, are needed.

Changes in the six most common sequence types of Neisseria gonorrhoeae, including ST4378, identified by surveillance of antimicrobial resistance in northern Taiwan from 2006 to 2013.

BACKGROUND: There has been no longitudinal study of drug susceptibility in Neisseria gonorrhoeae in Taiwan since 2006. METHODS: We collected 1090 gonococcal isolates from Taipei City Hospital, Taiwan from April 2006 to August 2013. We used a disk diffusion assay to determine the susceptibility to five antibiotics and an E-test to determine the minimum inhibitory concentrations for cefixime and ceftriaxone in isolates with resistance. Neisseria gonorrhoeae-multi Antigen Sequence Typing and DNA sequencing of the por and tbpB genes were used to identify sequence types. RESULTS: Among the 1090 isolates, the resistances to penicillin, ciprofloxacin, cefpodoxime, cefixime, and ceftriaxone were 61.01%, 83.39%, 9.63%, 6.70%, and 2.39%, respectively. The highest minimum inhibitory concentrations of cefixime and ceftriaxone were 0.19 mg/L and 0.50 mg/L, respectively. There were 327 sequence types. The four most common sequence types in homosexuals were ST4378, ST359, ST4654, and ST547; the two most common sequence types in heterosexuals were ST421 and ST419. Each of these sequence types had more than 25 isolates. There were significant differences in the sequence types in patients with different sexual orientations (p < 0.001). CONCLUSION: Oral cefixime or ceftriaxone injections were used as first-line drugs for the treatment of gonorrhea from 2006 to 2013 because gonorrhea isolates had low minimum inhibitory concentrations for these two drugs. The abrupt emergence of ST4378 (closely related to the notorious ST1407) since 2009 is a cause for alarm. Changes in sexual behavior, including an increase in sexual activity without the use of condoms, may have contributed to the peak in gonorrhea in 2010. Further molecular epidemiological investigations are required.

Pregnancy outcomes of anti-hypertensives for women with chronic hypertension: a population-based study.

BACKGROUND: The impact of anti-hypertensive treatment on fetus was unclear, and hence, remains controversial. We set out in this study to estimate the prevalence of adverse pregnancy outcomes, including low birth weight, preterm delivery and small for gestational age amongst women with chronic hypertension, and to determine whether the use of anti-hypertensive drugs increases the risk of such adverse pregnancy outcomes. METHODOLOGY/PRINCIPAL FINDINGS: A total of 2,727 hypertension mothers and 8,181 matched controls were identified from the population-based cohort. These hypertension women were divided into seven sub-groups according to different types of prescribed anti-hypertensive drugs. Multivariable logistic regressions were conducted to estimate the risk of low birth weight, preterm birth and small for gestational age. Increased risk of low birth weight (OR = 2.29, 95% CI = 1.95-2.68), preterm birth (OR = 2.18, 95% CI = 1.89-2.52) and small for gestational age (OR = 1.62, 95% CI = 1.45-1.81) were all discernible within the hypertension group after adjusting for potential confounding factors. The increased ORs were found to differ with different types of anti-hypertensive drugs. Women who received vasodilators were associated with the highest risk of low birth weight (OR = 2.96, 95% CI = 2.06-4.26), preterm birth (OR = 2.92 95% CI = 2.06-4.15) and small for gestational age (OR = 2.12, 95% CI = 1.60-2.82). CONCLUSIONS/SIGNIFICANCE: This finding is important for practitioners, because it indicates the need for caution while considering the administration of anti-hypertensive drugs to pregnant women. These observations require confirmation in further studies that can better adjust for the severity of the underlying HTN.

Changes in compliance with recommended infection control practices and affecting factors among dentists in Taiwan.

Compliance with recommended infection control practices in East Asia has not been clearly documented. To investigate changes in compliance with recommended infection control practices over a eleven-year period and to identify affecting factors, two nationwide cross-sectional surveys of dentists in Taiwan were conducted in 1999 and 2010. An anonymous questionnaire that assessed characteristics of dentists and practices of recommended infection control guidelines was mailed. Results showed that all infection control practices surveyed had improved in 2010. Factors affecting compliance with wearing basic protective barriers in 2010 were being female (odds ratio [OR]=3.631, p<0.001), aged forty-one to fifty years (OR=3.991, p<0.05), treating twenty-one to thirty patients per day (OR=2.690, p<0.05), and having information sources from seminars and conferences (OR=2.659, p<0.05). Although infection control practices have improved over time, there is still much room to increase rates of wearing a head cap, protective eyewear, and a face mask and disinfecting impression materials. Providing correct information about disinfection and sterilization processes through the Internet might be effective in improving compliance.

Factors affecting occupational exposure to needlestick and sharps injuries among dentists in Taiwan: a nationwide survey.

BACKGROUND: Although the risks of needlestick and sharps injuries (NSIs) for dentists are well recognized, most papers published only described the frequency of occupational exposure to NSIs. Less has been reported assessing factors contributing to exposure to NSIs. The purpose of this study was to update the epidemiology of NSIs among dentists in Taiwan and identify factors affecting NSIs in order to find preventive strategies. METHODOLOGY/PRINCIPAL FINDINGS: A nationwide survey was conducted in dentists at 60 hospitals and 340 clinics in Taiwan. The survey included questions about factors supposedly affecting exposure to NSIs, such as dentist and facility characteristics, knowledge and attitudes about infectious diseases, and practices related to infection control. Univariate and multivariate logistic regression analyses were conducted to determine the association between risk factors and exposure to NSIs. In total, 434 (74.8%) of 580 dentists returned the survey questionnaires, and 100 (23.0%) reported that they had experienced more than one NSI per week. Our data showed that the risk of occupational NSIs is similarly heightened by an older age (odds ratio [OR], 3.18; 95% confidence interval [CI], 1.62-6.25), more years in practice (OR, 2.57; 95% CI, 1.41-4.69), working in clinics (OR, 1.73; 95% CI, 1.08-2.77), exhibiting less compliance with infection-control procedures (OR, 1.82; 95% CI, 1.04-3.18), having insufficient knowledge of blood-borne pathogens (OR, 1.67; 95% CI, 1.04-2.67), and being more worried about being infected by blood-borne pathogens (OR, 1.82; 95% CI, 1.05-3.13). CONCLUSIONS/SIGNIFICANCE: High rates of NSIs and low compliance with infection-control procedures highly contribute to the chance of acquiring a blood-borne pathogen infection and threaten occupational safety. This study reveals the possible affecting factors and helps in designing prevention strategies for occupational exposure to NSIs.

Risk of digoxin intoxication in heart failure patients exposed to digoxin-diuretic interactions: a population-based study.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Increased frequency of electrolyte abnormalities and cardiac arrhythmias among patients exposed to digoxin-diuretic interactions has been well-documented in numerous descriptive studies. * Nonetheless, a clear causal relationship has not been established in these studies. WHAT THIS STUDY ADDS * The risks of digoxin intoxication associated with use of digoxin in combination with any diuretic use, types of diuretics, combinations of diuretics, and individual diuretics were quantified using a population-based nested case-control study design. * The combined therapy of digoxin with any diuretic is associated with a 3.08-fold increase in the risk of digoxin intoxication. * Regarding diuretic class, the risk carried by loop diuretics is greater than that of thiazides or potassium-sparing diuretics, and the risk varies with different combinations of diuretic classes and individual diuretics. AIMS To quantify the digoxin intoxication risk associated with exposure to digoxin-diuretic interactions, and evaluate whether the risk varies by diuretic type, individually or in combination. METHODS This was a population-based nested case-control study in which data from the National Health Insurance Research Database (NHIRD) in Taiwan were analysed. RESULTS The study cohort comprised 154 058 heart failure (HF) patients taking digoxin between 2001 and 2004, in whom digoxin intoxication requiring a hospitalization (ICD-9 code 972.1) occurred in 595 cases. A total of 28 243 matched controls were also selected for analysis. Cases were 3.08 times (adjusted OR 3.08, 95% CI 2.50, 3.79) more likely to have been prescribed diuretic medication in the previous month than controls. Regarding the class of diuretics, loop diuretics carried the greatest risk (adjusted OR 2.97, 95% CI 2.35, 3.75), followed by thiazides (OR 2.36, 95% CI 1.70, 3.29) and potassium-sparing diuretics (OR 1.72, 95% CI 0.83, 3.56). The risk was also observed to vary with different combinations of diuretics, and the loops/thiazides/potassium-sparing diuretics combination carried the greatest risk (adjusted OR 6.85, 95% CI 4.93, 9.53). Among the individual diuretics examined, hydrochlorothiazide carried the greatest risk (adjusted OR 4.63, 95% CI 2.50, 8.57). CONCLUSIONS This study provided empirical evidence that digoxin-diuretic interactions increased the risk of hospitalization for digoxin intoxication in HF patients. The risk was particularly high for concomitant use of digoxin with a combination of loop diuretics, thiazide and potassium-sparing diuretics. The combined use of digoxin and diuretics should be avoided if possible.

Risk of digoxin intoxication caused by clarithromycin-digoxin interactions in heart failure patients: a population-based study.

OBJECTIVE: To quantify the effect of exposures to digoxin­clarithromycin interactions on the risk of digoxin toxicity requiring hospitalizations in a population-based manner in a Taiwanese population. METHODS: This is a retrospective population-based nested case­control study. Data were retrieved from the National Health Insurance Research Database. Heart failure (HF) patients newly treated with digoxin between 1 January 2001 and 31 December 2004 were retrieved from the database as the study cohort. Case patients, admitted to the hospitals with the diagnosis of digoxin intoxication (ICD-9 code 972.1) were identified from the study cohort and compared with the matched controls for the receipt of clarithromycin. RESULTS: A total of 154,058 patients were identified as the study cohort; from these, 595 cases and 27,020 matched controls were selected for study. The prescription of clarithromycin at 7, 14, and 30 days prior to the index date was associated with a 4.36- (95% CI 1.28­14.79), 5.07- (95% CI 2.36­10.89), and 2.98-fold (95% CI 1.59­5.63) increase in hospitalization for digoxin intoxication, respectively. The results of the dose­response relationship also indicated that clarithromycin prescribed with a prescribed daily dose (PDD)/defined daily dose (DDD) ratio >2 led to a 55.41-fold (95% CI 9.31­329.9) increase of the risk, which is significantly greater than that prescribed with a 1­2 PDD/DDD ratio (adjusted OR 4.81; 95% CI 1.88­12.30) or with a <1 PDD/DDD ratio (adjusted OR 0.78; 95% CI 0.19­3.20). CONCLUSION: This study provides empirical evidence that digoxin­clarithromycin interactions do increase the risk of hospitalization for digoxin intoxication in HF patients and that this risk could reach as high as 55.4-fold. We strongly recommend that the combined use of digoxin with clarithromycin should be avoided and that digoxin concentrations should be monitored closely in situations where the combination can not be avoided.