Airway Reactance Predicts Static Lung Hyperinflation in Severe Asthma.

BACKGROUND AND OBJECTIVES: Background: Static lung hyperinflation (SLH) measured using body plethysmography in patients with asthma is associated with poor outcomes. The severity of SLH may be associated with small airway dysfunction (SAD), which can be measured using impulse oscillometry (IOS). Objective: This study aims to determine the correlation between SLH and SAD in patients with severe asthma and assess the improvement in SLH and SAD with treatment. METHODS: We analyzed data from patients who were enrolled in the Taiwan Severe Asthma Registry, which comprises a prospective observational cohort. Plethysmography and IOS were performed regularly. The relationship between spirometry and IOS parameters was determined. Changes in the clinical outcomes in response to treatment were analyzed. RESULTS: Of 107 patients with severe asthma, 83 (77.6%) had SLH based on an increased residual volume to total lung capacity ratio (RV/ TLC). Most patients were older women with worse pulmonary function and SAD than those without SLH. SAD, defined as increased airway resistance/reactance, was significantly correlated with SLH. Airway reactance at 5 Hz (X5) ≤-0.21 kPa/(L/s) detected SLH with an area under the receiver operating characteristic curve of 0.84 (P<.0001; sensitivity, 85.2%; and specificity, 83.3%). After 12 months, patients who received add-on biologics (vs those who did not) had significantly reduced exacerbations, fractional exhaled nitric oxide level, and blood eosinophil counts, as well as improved forced expiratory volume in the first second, X5, and a trend toward reduced RV/TLC ratio. CONCLUSIONS: In severe asthma, airway reactance (X5) could be a novel parameter for assessing SLH.

Airway Reactance Predicts Static Lung Hyperinflation in Severe Asthma

Background: Static lung hyperinflation (SLH) measured using body plethysmography in patients with asthma is associated with poor outcomes. The severity of SLH may be associated with small airway dysfunction (SAD), which can be measured using impulse oscillometry (IOS). Objective: This study aims to determine the correlation between SLH and SAD in patients with severe asthma and assess the improvement in SLH and SAD with treatment. Methods: We analyzed data from patients who were enrolled in the Taiwan Severe Asthma Registry, which comprises a prospective observational cohort. Plethysmography and IOS were performed regularly. The relationship between spirometry and IOS parameters was determined. Changes in the clinical outcomes in response to treatment were analyzed. Results: Of 107 patients with severe asthma, 83 (77.6%) had SLH based on an increased residual volume to total lung capacity ratio (RV/TLC). Most patients were older women with worse pulmonary function and SAD than those without SLH. SAD, defined as increased airway resistance/reactance, was significantly correlated with SLH. Airway reactance at 5 Hz (X5) ≤−0.21 kPa/(L/s) detected SLH with an area under the receiver operating characteristic curve of 0.84 (P<.0001; sensitivity, 85.2%; and specificity, 83.3%). After 12 months, patients who received add-on biologics (vs those who did not) had significantly reduced exacerbations, fractional exhaled nitric oxide level, and blood eosinophil counts, as well as improved forced expiratory volume in the first second, X5, and a trend toward reduced RV/TLC ratio. Conclusion: In severe asthma, airway reactance (X5) could be a novel parameter for assessing SLH. (AU)

Antecedentes: En el asma bronquial, la hiperinsuflación pulmonar estática (SLH) medida mediante pletismografía corporal (Pleth) se asocia a un peor pronóstico. La gravedad de la SLH podría estar asociada con la disfunción de las vías respiratorias pequeñas (SAD), que puede medirse mediante la oscilometría de impulsos (IOS). Objetivo: Este estudio pretende determinar la correlación entre el SLH y la SAD en pacientes con asma grave, y la mejora de ambos parámetros en respuesta al tratamiento. Métodos: Se analizaron los datos de los pacientes que se inscribieron en el Registro de Asma Grave de Taiwán, una cohorte observacional prospectiva. Se realizaron periódicamente mediciones de Pleth e IOS. Se determinó la relación entre los parámetros espirométricos e IOS. Se analizaron los cambios en los parámetros clínicos y funcionales en respuesta al tratamiento. Resultados: De una muestra de 107 pacientes con asma grave, 83 (77,6%) presentaban SLH, definida mediante una relación volumen residual/capacidad pulmonar total (VR/CTP) aumentada. La mayoría de los pacientes eran mujeres de edad avanzada con peor función pulmonar y SAD, en comparación con los que no tenían SLH. El SAD por aumento de la resistencia/reactancia de las vías respiratorias se correlacionó significativamente con el SLH. La reactancia de las vías respiratorias a 5 Hz (X5) ≤-0,21 [kPa/(L/s)] detectó el SLH con un área bajo la curva ROC de 0,84 (p < 0,0001, sensibilidad = 85,2% y especificidad = 83,3%). Después de 12 meses, los pacientes que recibieron tratamiento biológico adicional presentaron una reducción significativa de las exacerbaciones, del nivel de óxido nítrico exhalado, del recuento de eosinófilos en sangre, una mejora del volumen espiratorio forzado en el primer segundo, de la X5, y una tendencia a la reducción del cociente RV/TLC en comparación con los que no recibieron tratamiento biológico... (AU)

Intermediate tidal volume is an acceptable option for ventilated patients with acute respiratory distress syndrome.

OBJECTIVE: Evidence only proves low surpasses high tidal volume (VT) for acute respiratory distress syndrome (ARDS). Intermediate VT is a common setting for ARDS patients and has been demonstrated as effective as low VT in non-ARDS patients. The effectiveness of intermediate VT in ARDS has not been studied and is the objective of this study. DESIGN: A retrospective cohort study. SETTING: Five ICUs with their totally 130 beds in Taiwan. PATIENTS OR PARTICIPANTS: ARDS patients under invasive ventilation. INTERVENTIONS: No. MAIN VARIABLES OF INTEREST: 28-D mortality. RESULT: Totally 382 patients, with 6958 ventilator settings eligible for lung protection, were classified into low (mean VT=6.7ml/kg), intermediate (mean VT=8.9ml/kg) and high (mean VT=11.2ml/kg) VT groups. With similar baseline ARDS and ICU severities, intermediate and low VT groups did not differ in 28-D mortality (47% vs. 63%, P=0.06) or other outcomes such as 90-D mortality, ventilator-free days, ventilator-dependence rate. Multivariate analysis revealed high VT was independently associated with 28-D and 90-D mortality, but intermediate VT was not significantly associated with 28-D mortality (HR 1.34, CI 0.92-1.97, P=0.13) or 90-D mortality. When the intermediate and low VT groups were matched in propensity scores (n=66 for each group), their outcomes were also not significantly different. CONCLUSION: Intermediate VT, with its outcomes similar to small VT, is an acceptable option for ventilated ARDS patients. This conclusion needs verification through clinical trials.

Association between transforming growth factors-ß and matrix metalloproteinases in the aqueous humor and plasma in myopic patients.

PURPOSE: To investigate the relationship between levels of transforming growth factor beta (TGF-beta), matrix metalloproteinase (MMP) and tissue inhibitors of MMP (TIMP) in the aqueous humor (AH) and plasma (PL) of myopic patients. METHODS: Aqueous humor and plasma were collected intraoperatively from 37 myopic patients with various axial lengths (AL) during ICL surgery. The concentrations of TGF-ß1, TGF-ß2, TGF-ß3, MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, TIMP-2, TIMP-3 and TIMP-4 were measured using Luminex xMAP Technology kits (Milliplex xMAP kits). The association between TGFß and MMP/TIMP levels were analyzed based on the Spearman's correlation test or Pearson's correlation test. RESULTS: There was a negative correlation between TGF-ß1 and MMP-1, TIMP-2, TIMP-3 and TIMP-4 in the AH, and a positive correlation between TGF-ß1 and MMP-1 in the PL. In the AH, levels of TGF-ß2 were positively correlated with levels of TIMP-3 (r=0.441; P < 0.001). In the PL, levels of TGF-ß2 also correlated positively with levels of TIMP-3 (r=0.427; P < 0.001)). CONCLUSION: The level of TGF-ß2 was the highest among TGF-ßs in the AH. A consistent positive correlation between TGF-ß2 and TIMP-3 was found both in the AH and PL, indicating that systemic levels of TGF-ß2 and MMPs/TIMPs may also play a role in myopic progression.

Intermediate tidal volume is an acceptable option for ventilated patients with acute respiratory distress syndrome / El volumen tidal intermedio es una opción aceptable para pacientes ventilados con síndrome de dificultad respiratoria aguda

Objective Evidence only proves low surpasses high tidal volume (VT) for acute respiratory distress syndrome (ARDS). Intermediate VT is a common setting for ARDS patients and has been demonstrated as effective as low VT in non-ARDS patients. The effectiveness of intermediate VT in ARDS has not been studied and is the objective of this study. Design A retrospective cohort study. Setting Five ICUs with their totally 130 beds in Taiwan. Patients or participants ARDS patients under invasive ventilation. Interventions No. Main variables of interest 28-D mortality. Result Totally 382 patients, with 6958 ventilator settings eligible for lung protection, were classified into low (mean VT=6.7ml/kg), intermediate (mean VT=8.9ml/kg) and high (mean VT=11.2ml/kg) VT groups. With similar baseline ARDS and ICU severities, intermediate and low VT groups did not differ in 28-D mortality (47% vs. 63%, P=0.06) or other outcomes such as 90-D mortality, ventilator-free days, ventilator-dependence rate. Multivariate analysis revealed high VT was independently associated with 28-D and 90-D mortality, but intermediate VT was not significantly associated with 28-D mortality (HR 1.34, CI 0.92–1.97, P=0.13) or 90-D mortality. When the intermediate and low VT groups were matched in propensity scores (n=66 for each group), their outcomes were also not significantly different. Conclusio Intermediate VT, with its outcomes similar to small VT, is an acceptable option for ventilated ARDS patients. This conclusion needs verification through clinical trials (AU)

Objetivo La evidencia solo demuestra que el volumen tidal (VT) bajo supera al alto para el síndrome de dificultad respiratoria aguda (ARDS). La VT intermedia es un escenario común para los pacientes con ARDS y se ha demostrado que es tan eficaz como la VT baja en pacientes sin ARDS. No se ha estudiado la eficacia de la VT intermedia en el ARDS y es el objetivo de este estudio. Diseño Un estudio de cohorte retrospectivo. Ámbito Cinco UCI con un total de 130 camas en Taiwán. Pacientes o participantes Pacientes con ARDS bajo ventilación invasiva. Intervenciones No. Variables de interés principales Mortalidad 28-D. Resultado Un total de 382 pacientes, con 6958 configuraciones de ventilador elegibles para protección pulmonar, se clasificaron en bajo (VT medio=6,7ml/kg), intermedio (VT medio=8,9ml/kg) y alto (VT medio=11,2ml/kg). Grupos de VT. Con un ARDS inicial similar y una gravedad en la UCI, los grupos de VT intermedia y baja no difirieron en la mortalidad 28-D (47% vs. 63%, p=0,06) u otros resultados como mortalidad 90-D, días sin ventilador, dependencia del ventilador índice. El análisis multivariado reveló que la VT alta se asoció de forma independiente con la mortalidad 28-D y 90-D, pero la VT intermedia no se asoció significativamente con la mortalidad 28-D (HR 1,34, IC 0,92-1,97, p=0,13) o la mortalidad 90-D. Cuando los grupos de VT intermedia y baja se emparejaron en puntajes de propensión (n=66 para cada grupo), sus resultados tampoco fueron significativamente diferentes. Conclusión La VT intermedia, con resultados similares a la VT pequeña, es una opción aceptable para pacientes con ARDS ventilados. Esta conclusión necesita verificación a través de ensayos clínicos (AU)

Intermediate tidal volume is an acceptable option for ventilated patients with acute respiratory distress syndrome.

Objective: Evidence only proves low surpasses high tidal volume (V T) for acute respiratory distress syndrome (ARDS). Intermediate V T is a common setting for ARDS patients and has been demonstrated as effective as low V T in non-ARDS patients. The effectiveness of intermediate V T in ARDS has not been studied and is the objective of this study. Design: A retrospective cohort study. Setting: Five ICUs with their totally 130 beds in Taiwan. Patients or participants: ARDS patients under invasive ventilation. Interventions: No. Main variables of interest: 28-D mortality. Result: Totally 382 patients, with 6958 ventilator settings eligible for lung protection, were classified into low (mean V T = 6.7 ml/kg), intermediate (mean V T = 8.9 ml/kg) and high (mean V T = 11.2 ml/kg) V T groups. With similar baseline ARDS and ICU severities, intermediate and low V T groups did not differ in 28-D mortality (47% vs. 63%, P = 0.06) or other outcomes such as 90-D mortality, ventilator-free days, ventilator-dependence rate. Multivariate analysis revealed high V T was independently associated with 28-D and 90-D mortality, but intermediate V T was not significantly associated with 28-D mortality (HR 1.34, CI 0.92-1.97, P = 0.13) or 90-D mortality. When the intermediate and low V T groups were matched in propensity scores (n = 66 for each group), their outcomes were also not significantly different. Conclusion: Intermediate V T, with its outcomes similar to small V T, is an acceptable option for ventilated ARDS patients. This conclusion needs verification through clinical trials.

Objetivo: La evidencia solo demuestra que el volumen tidal (VT) bajo supera al alto para el síndrome de dificultad respiratoria aguda (ARDS). La VT intermedia es un escenario común para los pacientes con ARDS y se ha demostrado que es tan eficaz como la VT baja en pacientes sin ARDS. No se ha estudiado la eficacia de la VT intermedia en el ARDS y es el objetivo de este estudio. Diseño: Un estudio de cohorte retrospectivo. Ámbito: Cinco UCI con un total de 130 camas en Taiwán. Pacientes o participantes: Pacientes con ARDS bajo ventilación invasiva. Intervenciones: No. Variables de interés principales: Mortalidad 28-D. Resultado: Un total de 382 pacientes, con 6958 configuraciones de ventilador elegibles para protección pulmonar, se clasificaron en bajo (VT medio = 6,7 ml/kg), intermedio (VT medio = 8,9 ml/kg) y alto (VT medio = 11,2 ml/kg). Grupos de VT. Con un ARDS inicial similar y una gravedad en la UCI, los grupos de VT intermedia y baja no difirieron en la mortalidad 28-D (47% vs. 63%, p = 0,06) u otros resultados como mortalidad 90-D, días sin ventilador, dependencia del ventilador índice. El análisis multivariado reveló que la VT alta se asoció de forma independiente con la mortalidad 28-D y 90-D, pero la VT intermedia no se asoció significativamente con la mortalidad 28-D (HR 1,34, IC 0,92-1,97, p = 0,13) o la mortalidad 90-D. Cuando los grupos de VT intermedia y baja se emparejaron en puntajes de propensión (n = 66 para cada grupo), sus resultados tampoco fueron significativamente diferentes. Conclusión: La VT intermedia, con resultados similares a la VT pequeña, es una opción aceptable para pacientes con ARDS ventilados. Esta conclusión necesita verificación a través de ensayos clínicos.

Effect of interfacial and edge roughness on magnetoelectric control of Co/Ni microdisks on PMN-PT(011).

Uniform magnetic behavior within arrays of magnetoelectric heterostructures is important for the development of reliable strain-mediated microdevices. Multiple mechanisms may contribute to observed nonuniform magnetization reversal including surface roughness, non-uniform strain, and fabrication induced imperfections. Here, Co/Ni microdisks of 7 µm diameter were produced on both [Pb(Mg1/3Nb2/3)O3]1-x-[PbTiO3]x with x = 0.3 nominal composition (PMN-30PT) (011) and Si substrates, and the out-of-plane magnetization reversal was characterized using magneto-optical Kerr effect (MOKE). Coercivity variation across the microdisks within the arrays was observed on both the PMN-30PT and Si specimens with zero electric field applied. Co/Ni microdisks on a PMN-30PT substrate displayed relatively larger coercivity than those on a Si substrate due to the surface roughness effect. Quasistatic electric fields of varying magnitude were applied to the PMN-30PT substrate to assess the dependence of the coercivity on electric field induced strain. Our results indicate that while coercivity decreases with the increase of electric field induced strain, interfacial and edge roughness combine to realize a prohibitively large coercivity to overcome within the Co/Ni microdisks as well as a broad distribution of coercive field across a patterned microdisk array.

Development of the Brief Geriatric Assessment for the General Practitioner.

OBJECTIVES: The study aimed to develop a brief geriatric assessment (BGA) tool for the general practitioner to evaluate geriatric syndromes in community-dwelling older adults. DESIGN: A cross-sectional study. SETTING: 58 communities from four aging cities in Taiwan. PARTICIPANTS: 1,258 community-dwelling older adults aged 65 years and above. MEASUREMENTS: The BGA targeted physical function impairment, cognitive impairment, and mood impairment. The cutoff values of physical function tests (handgrip strength and 6-meter walk test [6MWT]) were estimated by receiver operating characteristic analysis. Second, the diagnostic validity of the BGA was calculated in terms of sensitivity, specificity, and predictive values, which were compared to corresponding comprehensive geriatric assessment (CGA) items. Third, the associated risk factors of geriatric syndromes were selected using stepwise logistic regression. Finally, we combined items selected from literature and CGA and then proposed a practical BGA framework. RESULTS: The proposed BGA comprised dominant handgrip strength, 6MWT, self-report personal birthday, address, and telephone number, question 'Do you have depressive mood for the past two weeks?', Rinne tuning-fork tests, Snellen scale, and body mass index. It evaluated multidimensional aspects of geriatrics syndromes including physical, cognitive, mood, and sensory impairment, sarcopenia, and nutrition status. Sensitivities in the Taiwan BGA items ranged from 48% for dominant handgrip strength to 97.6% for 6MWT corresponding to physical impairment; 58.3% for cognitive impairment corresponding to Short Portable Mental Status Questionnaire; 62.7% for mood impairment corresponding to Geriatric Depression Scale. The Taiwan BGA for the general practitioner takes less than 10 minutes and is suitable in the community setting. CONCLUSION: Early management of geriatric syndromes in the community is important. The current study demonstrated a practical BGA tool for the general practitioner to comprehensively assess geriatric syndromes in community-dwelling older adults.

The risk of anti-osteoporotic agent-induced severe cutaneous adverse drug reactions and their association with HLA.

BACKGROUND: There is increasing use of anti-osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)-SCAR. OBJECTIVE: To characterize patients with AOA-SCAR and investigate the HLA association and utility of in vitro diagnostic methods. METHODS: We enrolled 16 cases with AOA-cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens-Johnson syndrome [SJS] and 2 with drug rash with eosinophilia and systemic symptoms [DRESS]) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA-SCAR, and tolerability to alternative drugs. We further performed literature review and meta-analysis on the HLA association of AOA-SCAR. RESULTS: Our data showed strontium ranelate is the most common causality of AOA-SCAR in Asian populations. There was no cross-hypersensitivity of SR-SCAR with other AOA. HLA genotyping showed that SR-SJS was most significantly associated with HLA-A*33:03 (Pc = 5.17 × 10-3 , OR: 25.97, 95% CI: 3.08-219.33). Meta-analysis showed that HLA-A*33:03 was associated with SR-SJS (P = 5.01 × 10-5 ; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR-SJS was 83.3%. CONCLUSIONS: Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA-A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR-SCAR in patients whose reaction developed while taking multiple drugs.

Quality validation of platelets obtained from the Haemonetics and Trima Accel automated blood-collection systems.

BACKGROUND: Platelet transfusion is required to treat haemo-oncology or trauma patients. Platelet apheresis (PA) performed with apheresis equipment has increased rapidly in recent years. Leucocyte-reduced platelet apheresis (LRPA) can reduce the risk of platelet refractoriness and febrile nonhemolytic transfusion reactions (FNHTRs) for transfusion. Accordingly, this study aimed to investigate and compare the platelet metabolic and functional responses between PA performed with Haemonetics and LRPA performed with Trima Accel cell separator. METHODS: The qualities of platelets collected through PA and LRPA were evaluated in terms of visual appearance, morphology, platelet-aggregation changes, metabolic activities, and bacterium-screening test during 5-day storage. Statistical analyses included two-sample t-test and generalised estimating equation(GEE) method. RESULTS: During 5-day storage in LRPA, residual leucocytes were all <1.0×106, and the parameters of platelet function were as follows: platelet aggregated to agonists such as adenosine 5'-diphosphate (ADP) and collagen, and the extent of shape change and pO2 showed no statistically significant difference between PA and LRPA. The hypotonic shock reaction (HSR) on days 0, 1, and 3 were significantly higher in LRPA than in PA (71.78±6.92 vs. 64.10±7.42; P=0.002; 71.53±8.98 vs. 62.96±9.84; P=0.007; 68.05±7.28 vs. 57.76±6.80; P<0.0001, respectively). Values of mean platelet volume (MPV) were statistically larger in PA than in LRPA on days 0, 1, and 3. On day 5, the swirling score was higher in LRPA than in PA. The mean lactate levels had no statistically significant difference between PA and LRPA. Moreover, no growth was observed through bacterium-screening test conducted on 40 samples. CONCLUSION: Comparison of LRPA and PA products collected from the Trima Accel and Haemonetics automated blood-collection systems, respectively, revealed that both products possessed good platelet qualities even though additional processes are needed to reduce leucocytes. Furthermore, investigating the outcomes of other apheresis instruments with focus on the safety of donors, products, and recipients is necessary.

Long-term comparison study of philtral ridge morphology with two different techniques of philtral reconstruction.

Cleft lip and/or cleft palate are the most common congenital craniofacial anomalies. Philtral ridge morphology is an important aesthetic component of unilateral cleft lip (UCL) repair. To this end, we have developed two techniques of philtral ridge reconstruction: (1) asymmetric mattress muscle sutures, and (2) overlapping mattress muscle sutures. The objective of this retrospective cohort study was to compare their outcomes in UCL repairs. Group I patients (n=30) underwent UCL repair before August 2003, including philtral ridge reconstruction by asymmetric mattress muscle sutures. Group II patients (n=30) underwent UCL repair after August 2003, including philtral ridge reconstruction by overlapping mattress muscle sutures. Philtral morphology was evaluated by ultrasonographic and three-dimensional photographic measurements, examining cleft side philtral projection and philtral ridge symmetry. These demonstrated that group II patients had better philtral column symmetry and projection on the cleft side when compared to group I. Overlapping mattress muscle sutures produced better philtral morphology in UCL repairs than asymmetric mattress muscle sutures.

Salispheres from Different Major Salivary Glands for Glandular Regeneration.

Dysfunctional salivary glands (SGs) are a clinical challenge due to the lack of effective treatments. Cell therapy with stem/progenitor cells may improve this situation by providing promising therapeutic solutions. Therefore, exploring abundant cellular sources is important. Three major pairs of SGs are located in different anatomic regions: the parotid glands, the submandibular glands, and the sublingual glands. Although SG stem/progenitor cells can be isolated and cultivated from all major SGs as salispheres, the differences among SG origins remain unclear. In this study, salispheres were successfully isolated from all major SGs. The salispheres demonstrated unique cellular features that originated from their native tissues. The characteristic expression profiles and cellular features of SG stem cells were demonstrated in all salispheres. When they were transplanted into irradiated animals, the salispheres were all capable of improving the saliva secretion that was disrupted by irradiation. Typical histologic structures could be observed in most parts of the treated glands, and the fibrotic environments of irradiated submandibular glands were remodeled by all salispheres regardless of origins. This study characterized the cellular features and in vivo effects of salispheres that were derived from different anatomic origins. The results suggest the possibility of functional redundancy among distinct pairs of major SGs, which is useful for the design of cell therapy to treat dysfunctional glandular organs.

Baryon decays to purely baryonic final states.

The LHCb collaboration has presented first experimental evidence that spin-carrying matter and antimatter differ. The study looked at four-body decays of the [Formula: see text] baryon. Differences in the behaviour of matter and antimatter are associated with the non-invariance of fundamental interactions under the combined charge-conjugation and parity transformations, known as CP violation. We discuss purely baryonic decay processes, i.e. decay processes involving only spin-carrying particles. They are yet unexplored elementary processes. Their study opens a new chapter of flavour physics in the route towards a better understanding of CP violation. It may help us understand the observed matter and antimatter asymmetry of the Universe.

Overexpression of AdeABC efflux pump associated with tigecycline resistance in clinical Acinetobacter nosocomialis isolates.

OBJECTIVES: Tigecycline non-susceptible Acinetobacter nosocomialis (TNAN) has been discovered in clinical isolates. The resistance-nodulation-cell division (RND)-type efflux system plays a major role in tigecycline non-susceptible Acinetobacter baumannii, but the mechanism in A. nosocomialis remains unknown. Our aim was to analyse the contribution of efflux-based tigecycline resistance in clinical A. nosocomialis isolates collected from multiple medical centres in Taiwan. METHODS: A total of 57 A. nosocomialis isolates, including 46 TNAN and 11 tigecycline-susceptible A. nosocomialis (TSAN) isolates, were analysed. Of these, 46 TNAN isolates were clustered to ST410 (43 isolates) and ST68 (three isolates) by multi-locus sequence typing. RESULTS: The relationship between the RND efflux pump and tigecycline resistance was indirectly verified by successfully reducing tigecycline resistance with NMP, an efflux pump inhibitor. The three RND efflux systems (AdeABC, AdeIJK and AdeFGH) were detected in all clinical isolates. The transcript level of adeB gene increased significantly and was correlated with tigecycline resistance. Moreover, the AdeRS two-component system was further classified into four different types of AdeRS patterns considering the amino acid sequence. Further analysis showed that tigecycline resistance was related to the transcript level of adeB gene and the AdeRS pattern. CONCLUSION: This study showed that the dissemination of TNAN isolates in Taiwan is attributable mainly to the spread of ST410. The AdeABC efflux pump appeared to play an important role in the tigecycline resistance of A. nosocomialis.

Effect of CoFe dusting layer and annealing on the magnetic properties of sputtered Ta/W/CoFeB/CoFe/MgO layer structures.

We explored the effect of a CoFe wedge inserted as a dusting layer (0.2 nm-0.4 nm thick) at the CoFeB/MgO interface of a sputtered Ta(2 nm)/W(3 nm)/CoFeB(0.9 nm)/MgO(3 nm)/Ta(2 nm) film-a typical structure for spin-orbit torque devices. Films were annealed at temperatures varying between 300 °C and 400 °C in an argon environment. Ferromagnetic resonance studies and vibrating sample magnetometry measurements were carried out to estimate the effective anisotropy field, the Gilbert damping, the saturation magnetization and the dead layer thickness as a function of the CoFe thickness and across several annealing temperatures. While the as-deposited films present only easy-plane anisotropy, a transition along the wedge from in-plane to out-of-plane was observed across several annealing temperatures, with evidence of a spin-reorientation transition separating the two regions.

Association of sperm source with miscarriage and take-home baby after ICSI in cryptozoospermia: a meta-analysis of testicular and ejaculated sperm.

BACKGROUND: Miscarriage and take-home baby are the most important issues to patients with cryptozoospermia in receiving intracytoplasmic sperm injection (ICSI). The ICSI usually use ejaculated or testicular sperm. Unfortunately, no synthesized evidence reported miscarriage and take-home baby rate between the two sperm sources. OBJECTIVES: This study aimed to compare the miscarriage and take-home baby rate of ICSI using testicular and ejaculated sperm in patient with cryptozoospermia. MATERIALS AND METHODS: We conducted meta-analyses that were based on data from Cochrane library, Ovid, PubMed, ScienceDirect, Scopus, and Web of Science. The pooled analyses used risk ratio (RR) in random-effects model. Sensitivity analyses by subgrouping were completed to explore the associations between mean age and outcome. RESULTS: This study identified 331 potential citations and included four cohort studies for qualitative and quantitative synthesis. The four studies involved 331 patients with 479 ICSI cycles. The results showed no significant difference in miscarriage between testicular sperm group and ejaculated sperm group (RR = 1.06, 95% CI 0.48-2.35, p = 0.88). Yet, take-home babies per embryo transfer in testicular sperm group (53/226, 23.45%) was more than ejaculated sperm group (59/429, 13.75%) (RR = 1.72, 95% CI 1.21-2.44, p = 0.002). Similar results can be found in take-home babies per ICSI cycle (RR = 1.77, 95% CI 1.28-2.44, p = 0.0005), especially in younger couple (RR = 1.93, 95% CI 1.11-3.34, p = 0.02). No small study bias was detected in the analyses. DISCUSSION: This study found that testicular sperm has more advantage for ICSI in patients with cryptozoospermia, especially in younger couple. These findings may help guide us when deciding the optimal method of sperm harvest for men with cryptozoospermia. CONCLUSION: Comparing to ejaculated sperm, testicular sperm showed benefits for take-home baby rate, but not for miscarriage in patients with cryptozoospermia.

Germline expression of the hunchback orthologues in the asexual viviparous aphids: a conserved feature within the Aphididae.

In animals, differentiation of germline from soma usually takes place during embryogenesis. Genes and their products that are preferentially expressed in the embryonic germ cells are regarded as candidates for maintaining germline fate or promoting germline identity. In Drosophila, for example, the protein encoded by the germline gene vasa is specifically restricted to the germ cells, while products of the gap gene hunchback (hb), a somatic gene, are preferentially expressed in the neuroblasts. In this study, we report the expression of both messenger RNA and protein encoded by Aphb, an hb orthologue in the asexual viviparous pea aphid Acyrthosiphon pisum, in germ cells as well as in neuroblasts. We infer that expression of Aphb messenger RNA in the germ cells during the formation of germaria is required for the anterior localization of Aphb in the protruding oocytes. Germarial expression and anterior localization of ApKrüppel was also identified but, unlike Aphb, its expression was not detected in the migrating germ cells. Very similar patterns of hb expression were also identified in the green peach aphid Myzus persicae, suggesting that germline expression of hb is conserved within the Aphididae. To date, this pattern of hb germline expression has not been reported in other insects.

HLJ1 is an endogenous Src inhibitor suppressing cancer progression through dual mechanisms.

HLJ1 (DNAJB4), a DNAJ/Hsp40 chaperone, has emerged as a novel prognostic marker in lung cancers; however, the molecular contribution and functionality in neoplastic diseases remain to be established. This study demonstrated that HLJ1 inhibits epithelial-mesenchymal transition in vitro and reduces lung cancer metastasis in vivo. Using shRNA silencing and ectopic expression of HLJ1, we found that HLJ1 not only suppresses catalytic activity of Src but also downregulates the formation of oncogenic complexes associated with the EGFR, FAK and STAT3 signaling pathways. A screen of specimens from HLJ1-knockout mice and lung cancer patients validated that HLJ1 expression is inversely correlated with Src activity. Mechanistically, HLJ1 protein directly bound to catalytic and protein-binding domains of Src through its amino acid Y172 and the P301/P304 motif. Following Src-induced HLJ1 phosphorylation at Y172, HLJ1-Src interaction was elevated, resulting in Src inhibition and malignancy suppression. Interestingly, both Src-binding regions also occurred in other DNAJB family members and contributed to anti-invasive activities of DNAJB proteins. We conclude that HLJ1 is an endogenous Src inhibitor that can suppress cancer metastasis through complex interacting mechanisms. This HLJ1-Src complex might provide a promising molecular model for developing new anticancer strategies.

Monte Carlo simulations of the relative biological effectiveness for DNA double strand breaks from 300 MeV u(-1) carbon-ion beams.

Monte Carlo simulations are used to calculate the relative biological effectiveness (RBE) of 300 MeV u(-1) carbon-ion beams at different depths in a cylindrical water phantom of 10 cm radius and 30 cm long. RBE values for the induction of DNA double strand breaks (DSB), a biological endpoint closely related to cell inactivation, are estimated for monoenergetic and energy-modulated carbon ion beams. Individual contributions to the RBE from primary ions and secondary nuclear fragments are simulated separately. These simulations are based on a multi-scale modelling approach by first applying the FLUKA (version 2011.2.17) transport code to estimate the absorbed doses and fluence energy spectra, then using the MCDS (version 3.10A) damage code for DSB yields. The approach is efficient since it separates the non-stochastic dosimetry problem from the stochastic DNA damage problem. The MCDS code predicts the major trends of the DSB yields from detailed track structure simulations. It is found that, as depth is increasing, RBE values increase slowly from the entrance depth to the plateau region and change substantially in the Bragg peak region. RBE values reach their maxima at the distal edge of the Bragg peak. Beyond this edge, contributions to RBE are entirely from nuclear fragments. Maximum RBE values at the distal edges of the Bragg peak and the spread-out Bragg peak are, respectively, 3.0 and 2.8. The present approach has the flexibility to weight RBE contributions from different DSB classes, i.e. DSB0, DSB+ and DSB++.

Mortality of breast cancer in Taiwan, 1971-2010: temporal changes and an age-period-cohort analysis.

The current paper describes the age, period and cohort effects on breast cancer mortality in Taiwan. Female breast cancer mortality data were collected from the Taiwan death registries for 1971-2010. The annual percentage changes, age- standardised mortality rates (ASMR) and age-period-cohort model were calculated. The mortality rates increased with advancing age groups when fixing the period. The percentage change in the breast cancer mortality rate increased from 54.79% at aged 20-44 years, to 149.78% in those aged 45-64 years (between 1971-75 and 2006-10). The mortality rates in the 45-64 age group increased steadily from 1971 to 1975 and 2006-10. The 1951 birth cohorts (actual birth cohort; 1947-55) showed peak mortalities in both the 50-54 and 45-49 age groups. We found that the 1951 birth cohorts had the greatest mortality risk from breast cancer. This might be attributed to the DDT that was used in large amounts to prevent deaths from malaria in Taiwan. However, future researches require DDT data to evaluate the association between breast cancer and DDT use.