Temporally modulating laser pulses to stabilize LIBS measurement locations under large gas temperature gradients.

In combustion research, laser-induced breakdown spectroscopy (LIBS) has been widely employed in local equivalence ratio measurement. However, the potential temperature gradients in the probe volume can significantly affect the shape of induced plasmas, resulting in unstable measurement locations. In this work, we improved the stability of measurement locations by modulating the laser pulse duration. In a hot-cold gas flow interface with large temperature gradients, when using the original laser pulse with a full width at half maximum (FWHM) of 4 ns, the locations of initial plasma core were insensitive to gradient variations; however, the plasma expansion behaviors differed significantly after 3 ns. The hot spots of plasmas diverged bi-directionally under high temperature, resulting in two-lobe structures and unstable measurement locations. After the laser pulse was modulated to a shorter duration using a pressure chamber, the plasma expansion was suppressed which constrained the plasma volume. Specifically, using a modulated pulse with a FWHM of 1.9 ns, the two-lobe structure was eliminated across the interface, and the standard deviation of measurement locations was reduced to 0.27 mm. The measured equivalence ratios across the interface showed favorable agreement with the simulation.

The long-term efficacy of eltrombopag in children with immune thrombocytopenia.

Immune thrombocytopenia (ITP) is the most common autoimmune disorder characterized by decreased platelet counts and impaired platelet production. Eltrombopag has been demonstrated to be safe and effective for children with ITP. It is reported eltrombopag can achieve a sustained response off treatment. However, data on its overall efficacy and safety profile are scarce in children. This study aimed to investigate the long-term efficacy of eltrombopag in children with ITP. Treatment overall response (OR), complete response (CR), response (R), durable response (DR), no response (NR), treatment free remission (TFR), and relapse rate, were assessed in 103 children with ITP during eltrombopag therapy. The OR rate, CR rate, R rate, DR rate, NR rate, TFR rate, and relapse rate were 67.0%, 55.3%, 11.7%, 56.3%, 33.0%, 60%, 36.2%, respectively. Importantly, we discovered that newly diagnosed ITP patients showed a higher DR rate, TFR rate and lower relapse rate compared to persistent and chronic ITP patients. Furthermore, the CR rate, DR rate, and TFR rate of 5 patients under six months were 100%. None of them suffered relapse. The most common adverse event (AEs) was hepatotoxicity (7.77%). Our study highlighted the critical role of eltrombopag as the second-line treatment in children with ITP who were intolerant to first-line therapy.

Acoustic characteristics of laser-induced plasmas from the forming dynamics perspective.

The acoustic signal has demonstrated its capabilities in assisting laser-induced breakdown spectroscopy (LIBS) measurements. In this study, the acoustic characteristics of laser-induced plasmas (LIPs) under different levels of energy deposition were analyzed, and their correlation with LIP forming dynamics was investigated. In the deposited energy space, two zones in the acoustic pressure and duration were observed, featuring a clear transition point in 100 mJ. The analysis based on self-emission spectra and images suggested that this transition is a result of the change in plasma forming dynamics. Above 100mJ, the plasma temperature and electron density were saturated; thus, any further increase in deposited energy only contributes to the plasma size. In this regime, the acoustic wave from the significantly elongated plasma no longer satisfied the ideal spherical assumption. The observation was also strengthened by the analysis in the frequency domain. Moreover, the correlation between acoustic and radiation signals was also changed significantly with plasma forming dynamics. This study offers a systematic analysis of LIP acoustic signals on the deposited energy space. The potential of using acoustic measurement to interpret the plasma forming dynamics was demonstrated, which could be beneficial for the successful implementations of acoustic-aided LIBS.

Emerging Hypervirulent Marek's Disease Virus Variants Significantly Overcome Protection Conferred by Commercial Vaccines.

As one of the most important avian immunosuppressive and neoplastic diseases, Marek's disease (MD), caused by oncogenic Marek's disease virus (MDV), has caused huge economic losses worldwide over the past five decades. In recent years, MD outbreaks have occurred frequently in MD-vaccinated chicken flocks, but the key pathogenic determinants and influencing factors remain unclear. Herein, we analyzed the pathogenicity of seven newly isolated MDV strains from tumor-bearing chickens in China and found that all of them were pathogenic to chicken hosts, among which four MDV isolates, SDCW01, HNXZ05, HNSQ05 and HNSQ01, were considered to be hypervirulent MDV (HV-MDV) strains. At 73 days of the virus infection experiment, the cumulative incidences of MD were 100%, 93.3%, 90% and 100%, with mortalities of 83.3%, 73.3%, 60% and 86.7%, respectively, for the four viruses. The gross occurrences of tumors were 50%, 33.3%, 30% and 63.3%, respectively, accompanied by significant hepatosplenomegaly and serious atrophy of the immune organs. Furthermore, the immune protection effects of four commercial MD vaccines against SDCW01, CVI988, HVT, CVI988+HVT, and 814 were explored. Unexpectedly, during the 67 days of post-virus challenge, the protection indices (PIs) of these four MD vaccines were only 46.2%, 38.5%, 50%, and 28%, respectively, and the birds that received the monovalent CVI988 or HVT still developed tumors with cumulative incidences of 7.7% and 11.5%, respectively. To our knowledge, this is the first demonstration of the simultaneous comparison of the immune protection efficacy of multiple commercial MD vaccines with different vaccine strains. Our study revealed that the HV-MDV variants circulating in China could significantly break through the immune protection of the classical MD vaccines currently widely used. For future work, there is an urgent need to develop novel, more effective MD vaccines for tackling the new challenge of emerging HV-MDV strains or variants for the sustainable control of MD.

A stem group Codium alga from the latest Ediacaran of South China provides taxonomic insight into the early diversification of the plant kingdom.

BACKGROUND: In recent years, Precambrian lifeforms have generated an ever-increasing interest because they revealed a rich eukaryotic diversity prior to the Cambrian explosion of modern animals. Among them, macroalgae are known to be a conspicuous component of Neoproterozoic ecosystems, and chlorophytes in particular are already documented in the Tonian, when they were so far expected to originate. However, like for other major eukaryotic lineages, and despite predictions of molecular clock analyses placing roots of these lineages well into the Neoproterozoic, a taxonomic constraint on Precambrian green algae has remained difficult. RESULTS: Here, we present an exceptionally preserved spherical, coenocytic unicellular alga from the latest Ediacaran Dengying Formation of South China (> ca. 541 Ma), known from both external and internal morphology, fully tridimensional and in great detail. Tomographic X-ray and electronic microscopy revealed a characteristic medulla made of intertwined siphons and tightly packed peripheral utricles, suggesting these fossils belong to the Bryopsidales genus Codium. However, its distinctly smaller size compared to extant species leads us to create Protocodium sinense gen. et sp. nov. and a phylomorphospace investigation points to a possible stem group affinity. CONCLUSIONS: Our finding has several important implications. First, Protocodium allows for a more precise calibration of Archaeplastida and directly confirms that a group as derived as Ulvophyceae was already well diversified in various ecosystems prior to the Cambrian explosion. Details of tridimensional morphology also invite a reassessment of the identification of other Ediacaran algae, such as Chuaria, to better discriminate mono-versus multicellularity, and suggest unicellular Codium-like morphotypes could be much older and widespread. More broadly, Protocodium provides insights into the early diversification of the plant kingdom, the composition of Precambrian ecosystems, and the extreme longevity of certain eukaryotic plans of organization.

Pathogenicity and Pathotype Analysis of Henan Isolates of Marek's Disease Virus Reveal Long-Term Circulation of Highly Virulent MDV Variant in China.

In recent years, outbreaks of Marek's disease (MD) have been frequently reported in vaccinated chicken flocks in China. Herein, we have demonstrated that four Marek's disease virus (MDV) isolates, HN502, HN302, HN304, and HN101, are all pathogenic and oncogenic to hosts. Outstandingly, the HN302 strain induced 100% MD incidence, 54.84% mortality, and 87.10% tumor incidence, together with extensive atrophy of immune organs. Pathotyping of HN302 was performed in comparison to a standard very virulent (vv) MDV strain Md5. We found that both CVI988 and HVT vaccines significantly reduced morbidity and mortality induced by HN302 or Md5 strains, but the protection indices (PIs) provided by these two vaccines against HN302 were significantly lower (27.03%) or lower (33.33%) than that against Md5, which showed PIs of 59.89% and 54.29%, respectively. These data suggested that HN302 possesses a significant higher virulence than Md5 and at least could be designated as a vvMDV strain. Together with our previous phylogenetic analysis on MDV-1 meq genes, we have presently suggested HN302 to be a typical highly virulent MDV variant belonging to an independent Chinese branch. To our knowledge, this is the first report to provide convincible evidence to identify a pathogenic MDV variant strain with a higher virulence than Md5 in China, which may have emerged and circulating in poultry farms in China for a long time and involved in the recent MD outbreaks.

Monitoring the deposited energy in laser-induced plasmas with an acoustic approach.

The monitoring of energy deposition behavior during the plasma formation process is the basis of recently developed laser-induced breakdown thermometry techniques. Utilizing the acoustic waveforms from laser-induced plasmas, a method to monitor the deposited energy was proposed. The linear relationships between the acoustic energy and the deposited energy were established under four different focal lengths. After the distortions in the sound propagation were corrected, the applicable range of this method was extended to a deposited energy from 10 to 240 mJ. The further spectra analysis in the deposited energy space suggested that the total number density of excited species increased with the deposition energy, without significant fluctuations in plasma temperature in the high-energy region.

Marek's Disease Virus (Gallid alphaherpesvirus 2)-Encoded miR-M2-5p Simultaneously Promotes Cell Proliferation and Suppresses Apoptosis Through RBM24 and MYOD1-Mediated Signaling Pathways.

MicroRNAs (miRNAs) have been demonstrated for their involvement in virus biology and pathogenesis, including functioning as key determinants of virally-induced cancers. As an important oncogenic α-herpesvirus affecting poultry health, Marek's disease virus serotype 1 [Gallid alphaherpesvirus 2 (GaHV-2)] induces rapid-onset T-cell lymphomatous disease commonly referred to as Marek's disease (MD), an excellent biological model for the study of virally-induced cancer in the natural hosts. Previously, we have demonstrated that GaHV-2-encoded miRNAs (especially those within the Meq-cluster) have the potential to act as critical regulators of multiple processes such as virus replication, latency, pathogenesis, and/or oncogenesis. In addition to miR-M4-5p (miR-155 homolog) and miR-M3-5p, we have recently found that miR-M2-5p possibly participate in inducing MD lymphomagenesis. Here, we report the identification of two tumor suppressors, the RNA-binding protein 24 (RBM24) and myogenic differentiation 1 (MYOD1), being two biological targets for miR-M2-5p. Our experiments revealed that as a critical miRNA, miR-M2-5p promotes cell proliferation via regulating the RBM24-mediated p63 overexpression and MYOD1-mediated IGF2 signaling and suppresses apoptosis by targeting the MYOD1-mediated Caspase-3 signaling pathway. Our data present a new strategy of a single viral miRNA exerting dual role to potentially participate in the virally-induced T-cell lymphomagenesis by simultaneously promoting the cell proliferation and suppressing apoptosis.

Bilateral Genu Valgum in an Adolescent with Primary Hyperparathyroidism: A Case Report and Review of Literature.

Primary hyperparathyroidism in children and adolescents is rare and often symptomatic at presentation. A 15-year-old bo presented with bilateral genu valgum for two years. Biochemical results were consistent with primary hyperparathyroidism Calcium levels normalized two months after removal of a left inferior parathyroid adenoma.

MECHANISMS OF ENDOCRINOLOGY: Endocrinology of opioids

The use of opioids has grown substantially over the past two decades reaching the dimensions of a global epidemic. These drugs have effects on multiple levels of the endocrine system through mechanisms which are still not fully elucidated, and awareness of their endocrine sequelae is vital for all specialists prescribing or managing patients on them. Hypogonadism is the most well-recognised consequence of opioid use (prevalence 21­86%) which, however, may remain undiagnosed with potential adverse outcomes for the patients. Although less frequent, cortisol deficiency can also be found. Furthermore, there is a negative impact on bone health (with reduced bone mineral density and increased fracture risk) and occasionally hyperprolactinaemia, whereas the clinical significance of alterations in other hormones remains to be clarified. Discontinuation or reduction of the opioid and, in cases of chronic pain, consideration of alternative therapies for pain relief are potential management options. Hormonal replacement, especially when the above measures are not practically feasible, needs to be considered. Further studies are needed to clearly establish the prevalence of hormonal abnormalities with various regimes, doses and routes of opioids and to address reliably the long-term benefits and risks of hormonal treatment in patients on opioids. Until evidence-based, safe and cost-effective clinical guidelines become available, periodical assessment of the gonadal and adrenal function (particularly when relevant clinical manifestations are present) and evaluation of the bone health status are advised.

Fluconazole as a Safe and Effective Alternative to Ketoconazole in Controlling Hypercortisolism of Recurrent Cushing's Disease: A Case Report.

INTRODUCTION: Ketoconazole has long been the first-line medical therapy for controlling hypercortisolism secondary to either pituitary or adrenal pathology. However, it is largely unavailable in most countries. As a result, we have turned to fluconazole as a viable alternative in view of its favourable safety profile. CASE PRESENTATION: A 50-year-old lady developed recurrent Cushing's disease after being in remission following transsphenoidal surgery (TSS) for a left pituitary microadenoma 16 years ago. The repeat MRI showed a right pituitary microadenoma (1.7 mm × 1.3 mm) for which she underwent a second TSS. However, she continued to have persistent hypercortisolism despite repeated MRIs showing absence of tumour recurrence. She refused bilateral adrenalectomy and external radiotherapy. Ketoconazole was commenced at 200 mg twice daily for disease control but this was hindered by intolerable side effects including pruritus and skin exfoliation. In the meantime, she suffered a right hypertensive basal ganglia hemorrhage. Treatment was subsequently switched to cabergoline and the dose titrated to 0.5 mg daily. Fluconazole 400 mg daily was later added to control the persistent disease. Her clinical and biochemical parameters improved markedly three months after the addition of fluconazole. No adverse event was reported. Her disease has remained stable for the last 15 months up until the time of the recent clinic review. CONCLUSIONS: This case demonstrates the long-term efficacy of fluconazole in tandem with cabergoline for the control of recurrent Cushing's disease.

A rare challenging case of co-existent craniopharyngioma, acromegaly and squamous cell lung cancer.

Co-existence of craniopharyngioma and acromegaly has been very rarely reported. A 65-year-old man presented with visual deterioration, fatigue and frontal headaches. Magnetic resonance imaging revealed a suprasellar heterogeneous, mainly cystic, 1.9 × 2 × 1.9 cm mass compressing the optic chiasm and expanding to the third ventricle; the findings were consistent with a craniopharyngioma. Pituitary hormone profile showed hypogonadotropic hypogonadism, mildly elevated prolactin, increased insulin-like growth factor 1 (IGF-1) and normal thyroid function and cortisol reserve. The patient had transsphenoidal surgery and pathology of the specimen was diagnostic of adamantinomatous craniopharyngioma. Post-operatively, he had diabetes insipidus, hypogonadotropic hypogonadism and adrenocorticotropic hormone and thyroid-stimulating hormone deficiency. Despite the hypopituitarism, his IGF-1 levels remained elevated and subsequent oral glucose tolerance test did not show complete growth hormone (GH) suppression. Further review of the pre-operative imaging revealed a 12 × 4 mm pituitary adenoma close to the right carotid artery and no signs of pituitary hyperplasia. At that time, he was also diagnosed with squamous cell carcinoma of the left upper lung lobe finally managed with radical radiotherapy. Treatment with long-acting somatostatin analogue was initiated leading to biochemical control of the acromegaly. Latest imaging has shown no evidence of craniopharyngioma regrowth and stable adenoma. This is a unique case report of co-existence of craniopharyngioma, acromegaly and squamous lung cell carcinoma that highlights diagnostic and management challenges. Potential effects of the GH hypersecretion on the co-existent tumours of this patient are also briefly discussed. LEARNING POINTS: Although an extremely rare clinical scenario, craniopharyngioma and acromegaly can co-exist; aetiopathogenic link between these two conditions is unlikely.Meticulous review of unexpected biochemical findings is vital for correct diagnosis of dual pituitary pathology.The potential adverse impact of GH excess due to acromegaly in a patient with craniopharyngioma (and other neoplasm) mandates adequate biochemical control of the GH hypersecretion.

Highly efficient generation of 0.2 mJ terahertz pulses in lithium niobate at room temperature with sub-50 fs chirped Ti:sapphire laser pulses.

We demonstrate generation of 0.2 mJ terahertz (THz) pulses in lithium niobate driven by Ti:sapphire laser pulses at room temperature. Employing tilted pulse front technique, the 800 nm-to-THz energy conversion efficiency has been optimized to 0.3% through chirping the sub-50 fs pump laser pulses to overcome multi-photon absorption and to extend effective interaction length for phase matching. Our approach paves the way for mJ-level THz generation via optical rectification using existing Ti:sapphire laser systems which can deliver Joule-level pulse energy with sub-50 fs pulse duration.

Biochemical properties and aggregation propensity of transforming growth factor-induced protein (TGFBIp) and the amyloid forming mutants.

TGFBI-associated corneal dystrophies are characterized by accumulation of insoluble deposits of the mutant protein transforming growth factor ß-induced protein (TGFBIp) in the cornea. Depending on the nature of mutation, the lesions appear as granular (non-amyloid) or lattice lines (amyloid) in the Bowman's layer or in the stroma. This review article emphasizes the structural biology aspects of TGFBIp. We discuss the tinctorial properties and ultrastructure of deposits observed in granular and lattice corneal dystrophic mutants with amyloid and non-amyloid forms of other human protein deposition diseases and review the biochemical and putative functional role of the protein. Using bioinformatics tools, we identify intrinsic aggregation propensity and discuss the possible protective role of gatekeepers close to the "aggregation-prone" regions of native TGFBIp. We describe the relative aggregation rates of lattice corneal dystrophy (LCD) and granular corneal dystrophy (GCD2) mutants using the three-parameter model, which is based on intrinsic properties of polypeptide chains. The predictive power of this model is compared with two other algorithms. We conclude that the model is able to predict the aggregation rate of mutants which do not alter overall net charge of the protein. The need to understand the mechanism of corneal dystrophies from the structural biology viewpoint is emphasized.

Clinical and genetic aspects of the TGFBI-associated corneal dystrophies.

Corneal dystrophies are a group of inherited disorders localized to various layers of the cornea that affect corneal transparency and visual acuity. The deposition of insoluble protein materials in the form of extracellular deposits or intracellular cysts is pathognomic. Mutations in TGFBI are responsible for superficial and stromal corneal dystrophies. The gene product, transforming growth factor ß induced protein (TGFBIp) accumulates as insoluble deposits in various forms. The severity, clinicopathogenic variations, age of the onset, and location of the deposits depend on the type of amino acid alterations in the protein. Until 2006, 38 different pathogenic mutants were reported for the TGFBI-associated corneal dystrophies. This number has increased to 63 mutants, reported in more than 30 countries. There is no effective treatment to prevent, halt, or reverse the deposition of TGFBIp. This review presents a complete mutation update, classification of phenotypes, comprehensive reported incidents of various mutations, and current treatment options and their shortcomings. Future research directions and possible approaches to inhibiting disease progression are discussed.

Distance effect of matrix attachment regions on transgene expression in stably transfected Chinese hamster ovary cells.

The ß-globin matrix attachment regions (MARs) were inserted into the 5'-site of the eukaryotic expression vector cassette and DNA fragments 350 and 750 bp in length were inserted into the site to generate expression vectors with varying distances between the expression cassette and MAR. The vectors containing MARs increased chloramphenicol acetyltransferase (CAT) expression levels compared to the negative control vector lacking the MAR; the highest expression increase was 3.8-fold. A greater MAR-transgene distance (750 bp) correlated with a greater increase in transgene expression when compared to the control vector that lacked separation between the MAR and transgene. CAT gene copy numbers were higher in cells transformed with the vector possessing a smaller MAR-transgene distance (350 bp) than in cells belonging to the other three groups. However, MAR-induced transgene expression levels did not exhibit a direct relationship with gene copy number.

Descemet stripping automated endothelial keratoplasty after failed penetrating keratoplasty: survival, rejection risk, and visual outcome.

IMPORTANCE: Descemet stripping automated endothelial keratoplasty (DSAEK) for isolated endothelial dysfunction has become the preferred surgical option for many corneal surgeons. However, there are limited large-scale reports on DSAEK survival and clinical variables affecting the risk of rejection and failure after failed penetrating keratoplasty (PK). OBJECTIVE: To report the survival, risk factors for graft rejection and failure, and visual outcome of DSAEK after failed PK. DESIGN, SETTING, AND PARTICIPANTS: A multicenter retrospective interventional case series included patients recruited from 6 tertiary referral surgical centers: 3 in the United States, 2 in Europe, and 1 in Asia. A total of 246 consecutive eyes (246 patients) that underwent DSAEK after failed PK, with a minimum follow-up period of 1 month, was included. Data comprising demographic details, preoperative and postoperative risk factors, time to rejection, time to failure, and corrected distance visual acuity were collected. MAIN OUTCOMES AND MEASURES: Cumulative probability of graft survival, hazard ratio estimates for survival, and corrected distance visual acuity were determined. RESULTS: The mean (SD) recipient age was 63.2 (16.6) years and the median follow-up period was 17 months (interquartile range, 6-30 months). One-third of the grafts (n = 82) had follow-up data for more than 2 years; 18.3% had more than 1 failed PK before DSAEK. In total, 19.1% (47 of 246) of DSAEK grafts failed. The cumulative probability of DSAEK survival after a failed PK was 0.89 (95% CI, 0.84-0.92), 0.74 (95% CI, 0.64-0.81), and 0.47 (95% CI, 0.29-0.61) at 1 year, 3 years, and 5 years, respectively. Based on multivariate analysis, significant preoperative risk factors for failure were young recipient age (hazard ratio [HR], 5.18 [95% CI, 1.57-17.18]), previous tube filtration surgery (HR, 5.23 [95% CI, 1.47-7.33]), and rejection episodes before PK failure (HR, 3.28 [95% CI, 1.47-7.33]); single-surgeon centers had a protective effect. Any rejection episode prior to PK failure was a significant predictor of post-DSAEK rejection, which in turn was a significant predictor of DSAEK failure. After a median follow-up of 17 months, 33.3% of the grafts achieved 0.3 or greater logMAR (20/40) corrected distance visual acuity. CONCLUSIONS AND RELEVANCE: Descemet stripping automated endothelial keratoplasty after failed PK combines greater wound stability and reduced suture-related complications, with visual outcomes and graft survival rates comparable to those of a second PK.

[The short term therapeutic effects of radioactive (125)I seeds implantation for treatment of non-small-cell lung cancer].

OBJECTIVE: To explore influential factors of local therapeutic effect in CT guided brachytherapy of (125)I seeds for non-small-cell lung carcinoma (NSCLC). METHODS: Totally 141 primary NSCLC patients diagnosed by bronchoscope or puncture biopsy were treated with CT guided (125)I seeds implantation treatment from 2003 January to 2005 January. Among them, 26 patients were treated with seeds implantation only and remaining 115 combined with chemical therapy. Preplans were performed by using treatment planning system before the implantation. We took the implantation with the prescription dose of 80 - 110 Gy, 1 seed per 1 cm(3), under the guide of computed tomography. Six months after implantation treatment, CT graphs were taken to evaluate the therapeutic effect. RESULTS: All the patients were survival until 6 months after implantation, and 37 were complete remission, 93 were partial remissions. The effective rate was 92.2%. Among all the observed factors, pathologic type(F = 5.162, P = 0.023), dose of cover 100% tumor (D(100)) (F = 100.713, P = 0.000) and treatment methods (F = 16.205, P = 0.000) were the independent influent factors (P < 0.05). Among these, D(100) was the most important factor (P = 0.000). Single factor analysis indicated that pathologic type (χ(2) = 7.313, P = 0.007), D(100) (χ(2) = 71.6, P = 0.000) and treatment methods (χ(2) = 20.5, P = 0.000) were significant influent factors. Of all 141 cases, 24 had complications during or after implantation treatment, while no severe complications were reported. There was no significant correlation between complication and local therapeutic effect (P > 0.05). CONCLUSION: CT guided implantation of (125)I seeds for lung cancer has good clinical effects and few complications. D(100) is the most important factor to influence the local therapeutic effect. Implantation treatment combined with chemotherapy is an ideal measure for NSCLC treatment.