Generation of arbitrary vector vortex beams on a higher-order Poincaré sphere using a double-exposure polarization-multiplexed hologram.

The existing methods for the generation of arbitrary vector vortex beams often involve complex optical setups or intricate fabrication methods. In this Letter, we propose a novel, to the best of our knowledge, and simplified approach for the efficient generation of vector vortex beams using a polarization-multiplexed hologram fabricated on an azo-carbazole polymer using a simple double-exposure technique. The hologram generates a vector vortex beam when simply illuminated by a collimated beam and also allows for a seamless traversal across the entire higher-order Poincaré sphere (arbitrary vortex beam generation) just by modulating the polarization of an illuminating beam.

INJEX50 could improve the success rate of local anesthesia for arterial cannulation in the pediatric intensive care unit: A randomized, double-blind, single-center study.

BACKGROUND: Quick arterial cannulation is required in pediatric emergency situation, which require effective local anesthesia to avoid withdrawal movement. However, pediatric local anesthesia could be difficult because of withdrawal movement. Jet injectors, which are needleless and provide local anesthesia quickly, could be helpful for pediatric local anesthesia during arterial cannulation. AIMS: This study aimed to examine whether new jet injector "INJEX50" could improve the success rate of local anesthesia for arterial cannulation in pediatric intensive care unit compared with the current standard of care, infiltration using a 26-gauge needle. METHODS: This study was a randomized, double-blind, single-center study. Participants were infants and young children in the pediatric intensive care unit, who required an arterial line. Local anesthesia was performed with either a 26-gauge needle (group C) or INJEX50 (group I) before arterial cannulation. The primary outcome (success of local anesthesia) was the presence of withdrawal movement at the time of skin puncture for arterial cannulation. The secondary outcomes included rescue sedation during arterial cannulation. Data were analyzed using Fisher's exact test and the Mann-Whitney U-test, with values of p < .05 considered statistically significant. RESULTS: Seventy patients were randomly assigned to groups C and I. The local anesthesia success rate in group I (30/35 [86%]) was significantly higher than that in group C (15/35 [43%], odds ratio, 8.00; 95% confidence interval, 2.51-25.5; p = .0005). In conclusion, INJEX50 could improve success rate of local anesthesia for arterial cannulation in pediatric intensive care unit compared with 26-gauge needle.

Head cooling wrap could suppress the elevation of core temperature after cardiac surgery during forced-air warming in a pediatric intensive care unit: a randomized clinical trial.

PURPOSE: The main aim of the current trial was to explore our hypothesis that cooling head wraps lower the core temperature more effectively than ice packs on the head during forced-air warming after pediatric cardiac surgeries. METHODS: This study was a single-center Randomized Controlled Trial. Participants were children with a weight ≤ 10 kg and hyperthermia during forced-air warming after cardiac surgeries. When the core temperature reached 37.5 °C, ice packs on the head (group C) or a cooling head wrap (group H) were used as cooling devices to decrease the core temperature. The primary outcome was the core temperature. The secondary outcomes were the foot surface temperature and heart rate. We measured all outcomes every 30 min for 240 min after the patient developed hyperthermia. We conducted two-way ANOVA as a pre-planned analysis and also the Bonferroni test as a post hoc analysis. RESULTS: Twenty patients were randomly assigned to groups C and H. The series of core temperatures in group H were significantly lower than those in group C (p < 0.0001), and post hoc analysis showed that there was no significant difference in core temperatures at T0 between the two groups and statistically significant differences in all core temperatures at T30-240 between the two groups. There was no difference between the two groups' surface temperatures and heart rates. CONCLUSIONS: Compared to ice packs on the head, head cooling wraps more effectively suppress core temperature elevation during forced-air warming after pediatric cardiac surgery.

Cosmetic and shoulder functional outcomes in posterolateral minithoracotomy atrial septal defect closure: A retrospective study.

BACKGROUND AND AIM: Transcatheter device closure has become the first treatment option for atrial septal defects (ASD). Surgical ASD closure, although still implemented, is cosmetically inferior to transcatheter closure. This study aimed to evaluate the feasibility as well as short- and long-term clinical outcomes of the right posterolateral minithoracotomy approach for surgical ASD closure. METHODS: In total, 102 consecutive patients underwent posterolateral minithoracotomy for ASD between January 2014 and December 2021 at our center. Early surgical outcomes, cosmetic findings, and skin perception were evaluated over 1 year of postoperative follow-up using a self-satisfaction survey (1: very good, 2: good, 3: normal, 4: not good, 5: bad), Cavendish score, and shoulder joint function (angles of flexion, extension, and abduction). RESULTS: No patient required conversion to median sternotomy. Only one patient required reoperation due to bleeding. Postoperative echocardiography revealed no residual shunt at discharge in all patients. The mean follow-up period was 3.7 years (range: 0.3-7.1 years), during which the questionnaire was answered by 69 of 98 patients who were evaluated after more than 1 year. The mean self-satisfaction survey scores for cosmetic findings and skin perception were 1.3 ± 0.6 and 1.2 ± 0.5, respectively. The Cavendish score was under Grade 1 in all patients. Shoulder flexion and abduction were normal at 180° in all patients, except one, while extension was normal at 50° in all patients, except three. CONCLUSIONS: Our procedure achieved not only good early surgical outcomes but also excellent long-term cosmetic and shoulder function results.

Absent pulmonary valve with double-outlet left ventricle: a case report.

Absent pulmonary valve syndrome and double-outlet left ventricle are rare congenital anomalies, with, to the best of our knowledge, no cases reported to date. We present the treatment course in a patient with an absent pulmonary valve, double-outlet left ventricle, dextrocardia, hypoplastic right ventricle, valvular aortic stenosis, and bronchomalacia.

Aerosol boxes decrease aerosol exposure only in depressurized rooms during aerosol-generating procedures in a simulation study.

PURPOSE: The aim of this study was to compare aerosol exposure with or without an aerosol box in a pressurized/depressurized room during aerosol-generating procedures using an experimental model. METHODS: Cake flour (aerosol model) was expelled from an advanced life support training mannequin. The primary outcome measure was the number of 0.3-10 µm-sized particles at three locations corresponding to the physician, medical staff, and environmental aerosol exposure levels. The aerosol dispersion was visualized using a high-resolution video. The number of expelled particles was measured after artificial coughing during simulated tracheal intubation and extubation in four situations, with or without an aerosol box in a pressurized or depressurized room (≤ 2.5 Pa). RESULTS: The particles arising from tracheal intubation at the three positions in the four groups differed significantly in size (p < 0.05). The sizes of particles arising from extubation at the physicians' and medical staff's faces in the four groups differed significantly in size (p < 0.05). Post hoc analysis showed that the counts of all particles at the three positions were significantly lower in the depressurized room with an aerosol box than in the pressurized room without an aerosol box during tracheal intubation (p < 0.05 at three positions) and extubation (p < 0.05) at the physician's and medical staff's positions). Visual assessments supported these results. CONCLUSION: The aerosol box decreased the exposure of the aerosol to the physician, medical staff, and environment during aerosol-generating procedures in the depressurized room only.

Safety of an improved pediatric epidural tunneling technique for catheter shear.

BACKGROUND: Epidural tunneling could help with prolonged catheterization and be effective in preventing infection and dislodgement. However, epidural tunneling techniques carry a risk of catheter shear or needlestick injuries. AIMS: This study aimed to examine the safety of our epidural tunneling technique in terms of catheter shear. METHODS: This study was designed as a double-blinded, single-crossover, in vitro study. Each of the operators performed two techniques to create a subcutaneous tunnel. We compared outcomes between the control tunneling technique (group C) and our improved technique (group I). Microscopic findings of catheter shear were assessed as the primary outcome. Secondary outcomes included the tension and displacement required to break the epidural catheter and the frequency of catheter breakage due to catheter shear. Data were analyzed using the Fisher's exact test and Mann-Whitney U test. A p-value of <.05 was considered statistically significant. RESULTS: Ten catheters were assessed in each group. The frequency of catheter shear was 10% in group I and 90% in group C (odds ratio, 0.019; 95% confidence interval [CI], 0.01-0.31; p < .001). The frequency of catheter breakage due to catheter shear was significantly lower in group I (0%) than in group C (80%; p < .001). The mean tension and displacement required to break the catheter were significantly higher in group I than in group C (4.13 ± 0.37 N vs. 3.14 ± 1.00 N; mean difference, 0.99 N; 95% CI, 0.25-1.73 N; p = .013 and 222 ± 59.9 mm vs. 122 ± 77.7 mm; mean difference, 100 mm; 95% CI, 34.1-165 mm; p = .005). CONCLUSIONS: Our improved epidural tunneling technique, which was designed for pediatric cases, could reduce the risk of catheter shear.

Thymine DNA glycosylase modulates DNA damage response and gene expression by base excision repair-dependent and independent mechanisms.

Thymine DNA glycosylase (TDG) is a base excision repair (BER) enzyme, which is implicated in correction of deamination-induced DNA mismatches, the DNA demethylation process and regulation of gene expression. Because of these pivotal roles associated, it is crucial to elucidate how the TDG functions are appropriately regulated in vivo. Here, we present evidence that the TDG protein undergoes degradation upon various types of DNA damage, including ultraviolet light (UV). The UV-induced degradation of TDG was dependent on proficiency in nucleotide excision repair and on CRL4CDT2 -mediated ubiquitination that requires a physical interaction between TDG and DNA polymerase clamp PCNA. Using the Tdg-deficient mouse embryonic fibroblasts, we found that ectopic expression of TDG compromised cellular survival after UV irradiation and repair of UV-induced DNA lesions. These negative effects on cellular UV responses were alleviated by introducing mutations in TDG that impaired its BER function. The expression of TDG induced a large-scale alteration in the gene expression profile independently of its DNA glycosylase activity, whereas a subset of genes was affected by the catalytic activity of TDG. Our results indicate the presence of BER-dependent and BER-independent functions of TDG, which are involved in regulation of cellular DNA damage responses and gene expression patterns.

Xeroderma pigmentosum group C protein interacts with histones: regulation by acetylated states of histone H3.

In the mammalian global genome nucleotide excision repair pathway, two damage recognition factors, XPC and UV-DDB, play pivotal roles in the initiation of the repair reaction. However, the molecular mechanisms underlying regulation of the lesion recognition process in the context of chromatin structures remain to be understood. Here, we show evidence that damage recognition factors tend to associate with chromatin regions devoid of certain types of acetylated histones. Treatment of cells with histone deacetylase inhibitors retarded recruitment of XPC to sites of UV-induced DNA damage and the subsequent repair process. Biochemical studies showed novel multifaceted interactions of XPC with histone H3, which were profoundly impaired by deletion of the N-terminal tail of histone H3. In addition, histone H1 also interacted with XPC. Importantly, acetylation of histone H3 markedly attenuated the interaction with XPC in vitro, and local UV irradiation of cells decreased the level of H3K27ac in the damaged areas. Our results suggest that histone deacetylation plays a significant role in the process of DNA damage recognition for nucleotide excision repair and that the localization and functions of XPC can be regulated by acetylated states of histones.

Influence of an Interfacial Effect on the Laser Performance of a Rhodamine 6G/Cellulose Acetate Waveguide on a Vinylidene Fluoride Copolymer Layer.

The fluorescent properties of dyes and fluorophores in condensed matter significantly affect the laser performance of organic dye lasers and fluorescent polymer lasers. Concentration quenching of fluorescence is commonly observed in condensed matter. Several approaches have been presented to suppress such quenching, such as the use of a dendrimer and the use of effective energy transfer in a guest-host system. The enhanced fluorescence of rhodamine 6G (R6G) dye on a vinylidene fluoride polymer is an alternative method for enhancing laser performance because of the roughness of the P(VDF-TrFE) surface and the interaction between polar ß-crystals of P(VDF-TrFE) and R6G dye. In this paper, a significant improvement in slope efficiency (SE) is demonstrated without a significant depression in the lasing threshold for distributed feedback (DFB) and distributed Bragg reflector (DBR) lasers fabricated using an R6G-dispersed cellulose acetate (CA) matrix spin-coated onto a copolymer of vinylidene fluoride and trifluoroethylene P(VDF-TrFE) thin film. SEs of 3.4 and 1.3% were measured for DBR and DFB laser devices with CA/R6G on a P(VDF-TrFE) thin film, respectively, whereas an SE of less than 1.0% was measured for both corresponding laser devices without a P(VDF-TrFE) thin film. From the aspect of simple fabrication procedures, repeatability in device fabrication and performance, stability of the device, time for device fabrication, the present approach is the most preferable way for industrial applications, requiring only the additional step of spin-coating of a P(VDF-TrFE) thin film.

Direct laser writing for micro-optical devices using a negative photoresist.

Direct laser writing (DLW) via two-photon absorption (TPA) has attracted much attention as a new microfabrication technique because it can be applied to fabricate complex, three-dimensional (3D) microstructures. In this study, 3D microstructures and micro-optical devices of micro-lens array on the micrometer scale are fabricated using the negative photoresist SU-8 through TPA with a femtosecond laser pulse under a microscope. The effects of the irradiation conditions on linewidths, such as laser power, writing speed, and writing cycles (a number of times a line is overwritten), are investigated before the fabrication of the 3D microstructures. Various microstructures such as woodpiles, hemisphere and microstructures, 3D micro-lens and micro-lens array for micro-optical devices are fabricated. The shape of the micro-lens is evaluated using the shape analysis mode of a laser microscope to calculate the working distance of the fabricated micro-lenses. The calculated working distance corresponds well to the experimentally measured value. The focusing performance of the fabricated micro-lens is confirmed by the TPA fluorescence of an isopropyl thioxanthone (ITX) ethanol solution excited by a Ti:sapphire femtosecond laser at 800 nm. Micro-lens array (assembled 9 micro-lenses) are fabricated. Nine independent woodpile structures are simultaneously manufactured by DLW via TPA to confirm the multi-focusing ability using the fabricated micro-lens array.

Functional regulation of the DNA damage-recognition factor DDB2 by ubiquitination and interaction with xeroderma pigmentosum group C protein.

In mammalian nucleotide excision repair, the DDB1-DDB2 complex recognizes UV-induced DNA photolesions and facilitates recruitment of the XPC complex. Upon binding to damaged DNA, the Cullin 4 ubiquitin ligase associated with DDB1-DDB2 is activated and ubiquitinates DDB2 and XPC. The structurally disordered N-terminal tail of DDB2 contains seven lysines identified as major sites for ubiquitination that target the protein for proteasomal degradation; however, the precise biological functions of these modifications remained unknown. By exogenous expression of mutant DDB2 proteins in normal human fibroblasts, here we show that the N-terminal tail of DDB2 is involved in regulation of cellular responses to UV. By striking contrast with behaviors of exogenous DDB2, the endogenous DDB2 protein was stabilized even after UV irradiation as a function of the XPC expression level. Furthermore, XPC competitively suppressed ubiquitination of DDB2 in vitro, and this effect was significantly promoted by centrin-2, which augments the DNA damage-recognition activity of XPC. Based on these findings, we propose that in cells exposed to UV, DDB2 is protected by XPC from ubiquitination and degradation in a stochastic manner; thus XPC allows DDB2 to initiate multiple rounds of repair events, thereby contributing to the persistence of cellular DNA repair capacity.

Effect of remifentanil during cardiopulmonary bypass on incidence of acute kidney injury after cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) after cardiopulmonary bypass (CPB) is a well-known postoperative complication. Remifentanil, which is a commonly used ultra-short-acting opioid, has antiinflammatory and sympatholytic effects with improvement of microcirculation. METHODS: A retrospective study was conducted to clarify the effect of the use of remifentanil during CPB on the incidence of postoperative AKI. Patients who underwent valve surgery while under cardiopulmonary bypass between January 2012 and December 2014 in our hospital were enrolled in this study. The incidences of postoperative AKI were compared in patients who received remifentanil during CPB (group R) and those who did not (group N). Univariate and multivariate regression analyses were performed to determine risk factors for AKI. RESULTS: Eighty patients received remifentanil (group R) and 50 patients did not (group N). The incidences of AKI were not significantly different in group R and group N (51% vs. 36%, P = 0.10). In multivariate regression analysis, age [adjusted odds ratio (OR) 1.048, 95% CI 1.008-1.089, P = 0.017], male gender (adjusted OR 3.101, 95% CI 1.303-7.378, P = 0.011), and use of preoperative calcium channel blockers (adjusted OR 3.240, 95% CI 1.302-8.063, P = 0.011) and diuretics (adjusted OR 2.673, 95% CI 1.178-6.066, P = 0.019) were associated with the incidence of AKI. The use of remifentanil was not associated with AKI (adjusted OR 2.321, 95% CI 0.997-5.402, P = 0.051). CONCLUSION: The use of remifentanil during CPB did not decrease the incidence of postoperative AKI after cardiac surgery.

Fabrication of gold microstructures using negative photoresists doped with gold ions through two-photon excitation.

The fabrication of gold microstructures was investigated using a mixture of SU-8 and gold ions using two-photon excitation induced by a femtosecond laser. Energy dispersive X-ray spectrometry, micro-X-ray diffraction and X-ray photoelectron spectroscopy were performed to analyse the resulting microstructures. Electrical conductivity was also measured. Elemental analysis showed that the fabricated structures consisted of triangular, reduced gold crystals and small amounts of cross-linked SU-8. The conductivity of the fabricated structures was four orders of magnitude lower than that of pure gold because of the cross-linked SU-8 present in the material.

A 10-year follow-up of a child with mild case of xeroderma pigmentosum complementation group D diagnosed by whole-genome sequencing.

BACKGROUND: Most patients with xeroderma pigmentosum complementation group D (XP-D) from Western countries suffer from neurological symptoms, whereas Japanese patients display only skin manifestations without neurological symptoms. We have previously suggested that these differences in clinical manifestations in XP-D patients are attributed partly to a predominant mutation in ERCC2, and the allele frequency of S541R is highest in Japan. METHODS: We diagnosed a child with mild case of XP-D by the evaluation of DNA repair activity and whole-genome sequencing, and followed her ten years. RESULTS: Skin cancer, mental retardation, and neurological symptoms were not observed. Her minimal erythema dose was 41 mJ/cm(2) , which was slightly lower than that of healthy Japanese volunteers. The patient's cells showed sixfold hypersensitivity to UV in comparison with normal cells. Post-UV unscheduled DNA synthesis was 20.4%, and post-UV recovery of RNA synthesis was 58% of non-irradiated samples, which was lower than that of normal fibroblasts. Genome sequence analysis indicated that the patient harbored a compound heterozygous mutation of c.1621A>C and c.591_594del, resulting in p.S541R and p.Y197* in ERCC2: then, patient was diagnosed with XP-D. Y197* has not been described before. CONCLUSION: Her mild skin manifestations might be attributed to the mutational site on her genome and daily strict sun protection. c.1621A>C might be a founder mutation of ERCC2 among Japanese XP-D patients, as it was identified most frequently in Japanese XP-D patients and it has not been found elsewhere outside Japan.

Structure-function analysis of the EF-hand protein centrin-2 for its intracellular localization and nucleotide excision repair.

Centrin-2 is an evolutionarily conserved, calmodulin-related protein, which is involved in multiple cellular functions including centrosome regulation and nucleotide excision repair (NER) of DNA. Particularly to exert the latter function, complex formation with the XPC protein, the pivotal NER damage recognition factor, is crucial. Here, we show that the C-terminal half of centrin-2, containing two calcium-binding EF-hand motifs, is necessary and sufficient for both its localization to the centrosome and interaction with XPC. In XPC-deficient cells, nuclear localization of overexpressed centrin-2 largely depends on co-overexpression of XPC, and mutational analyses of the C-terminal domain suggest that XPC and the major binding partner in the centrosome share a common binding surface on the centrin-2 molecule. On the other hand, the N-terminal domain of centrin-2 also contains two EF-hand motifs but shows only low-binding affinity for calcium ions. Although the N-terminal domain is dispensable for enhancement of the DNA damage recognition activity of XPC, it contributes to augmenting rather weak physical interaction between XPC and XPA, another key factor involved in NER. These results suggest that centrin-2 may have evolved to bridge two protein factors, one with high affinity and the other with low affinity, thereby allowing delicate regulation of various biological processes.

Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers.

Ovarian carcinomas with mutations in the tumour suppressor BRCA2 are particularly sensitive to platinum compounds. However, such carcinomas ultimately develop cisplatin resistance. The mechanism of that resistance is largely unknown. Here we show that acquired resistance to cisplatin can be mediated by secondary intragenic mutations in BRCA2 that restore the wild-type BRCA2 reading frame. First, in a cisplatin-resistant BRCA2-mutated breast-cancer cell line, HCC1428, a secondary genetic change in BRCA2 rescued BRCA2 function. Second, cisplatin selection of a BRCA2-mutated pancreatic cancer cell line, Capan-1 (refs 3, 4), led to five different secondary mutations that restored the wild-type BRCA2 reading frame. All clones with secondary mutations were resistant both to cisplatin and to a poly(ADP-ribose) polymerase (PARP) inhibitor (AG14361). Finally, we evaluated recurrent cancers from patients whose primary BRCA2-mutated ovarian carcinomas were treated with cisplatin. The recurrent tumour that acquired cisplatin resistance had undergone reversion of its BRCA2 mutation. Our results suggest that secondary mutations that restore the wild-type BRCA2 reading frame may be a major clinical mediator of acquired resistance to platinum-based chemotherapy.

The epistatic relationship between BRCA2 and the other RAD51 mediators in homologous recombination.

RAD51 recombinase polymerizes at the site of double-strand breaks (DSBs) where it performs DSB repair. The loss of RAD51 causes extensive chromosomal breaks, leading to apoptosis. The polymerization of RAD51 is regulated by a number of RAD51 mediators, such as BRCA1, BRCA2, RAD52, SFR1, SWS1, and the five RAD51 paralogs, including XRCC3. We here show that brca2-null mutant cells were able to proliferate, indicating that RAD51 can perform DSB repair in the absence of BRCA2. We disrupted the BRCA1, RAD52, SFR1, SWS1, and XRCC3 genes in the brca2-null cells. All the resulting double-mutant cells displayed a phenotype that was very similar to that of the brca2-null cells. We suggest that BRCA2 might thus serve as a platform to recruit various RAD51 mediators at the appropriate position at the DNA-damage site.