Critical reflections on the concept and impact of "scaling up" in Global Mental Health.

The field of Global Mental Health (GMH) aims to address the global burden of mental illness by focusing on closing the "treatment gap" faced by many low- and middle-income countries (LMICs). To increase access to services, GMH prioritizes "scaling up" mental health services, primarily advocating for the export of Western centred and developed biomedical and psychosocial "evidence-based" approaches to the Global South. While this emphasis on scalability has resulted in the increased availability of mental health services in some LMICs, there have been few critical discussions of this strategy. This commentary critically appraises the scalability of GMH by questioning the validity and sustainability of its approach. We argue that the current approach emphasizes the development of mental health services and interventions in "silos," focusing on the treatment of mental illnesses at the exclusion of a holistic and contextualized approach to people's needs. We also question the opportunities that the current approach to GMH offers for the growth of mental health programmes of local NGOs and investigate the potential pitfalls that scalability may have on NGOs' impact and ability to innovate. This commentary argues that any "scaling up" of mental health services must place sustainability at the core of its mission by favouring the growth and development of local solutions and wider forms of support that prioritize social inclusion and long-lasting mental health recovery.

Sound emission and annihilations in a programmable quantum vortex collider.

In quantum fluids, the quantization of circulation forbids the diffusion of a vortex swirling flow seen in classical viscous fluids. Yet, accelerating quantum vortices may lose their energy into acoustic radiations1,2, similar to the way electric charges decelerate on emitting photons. The dissipation of vortex energy underlies central problems in quantum hydrodynamics3, such as the decay of quantum turbulence, highly relevant to systems as varied as neutron stars, superfluid helium and atomic condensates4,5. A deep understanding of the elementary mechanisms behind irreversible vortex dynamics has been a goal for decades3,6, but it is complicated by the shortage of conclusive experimental signatures7. Here we address this challenge by realizing a programmable vortex collider in a planar, homogeneous atomic Fermi superfluid with tunable inter-particle interactions. We create on-demand vortex configurations and monitor their evolution, taking advantage of the accessible time and length scales of ultracold Fermi gases8,9. Engineering collisions within and between vortex-antivortex pairs allows us to decouple relaxation of the vortex energy due to sound emission and that due to interactions with normal fluid (that is, mutual friction). We directly visualize how the annihilation of vortex dipoles radiates a sound pulse. Further, our few-vortex experiments extending across different superfluid regimes reveal non-universal dissipative dynamics, suggesting that fermionic quasiparticles localized inside the vortex core contribute significantly to dissipation, thereby opening the route to exploring new pathways for quantum turbulence decay, vortex by vortex.

Tunneling Transport of Unitary Fermions across the Superfluid Transition.

We investigate the transport of a Fermi gas with unitarity-limited interactions across the superfluid phase transition, probing its response to a direct current (dc) drive through a tunnel junction. As the superfluid critical temperature is crossed from below, we observe the evolution from a highly nonlinear to an Ohmic conduction characteristic, associated with the critical breakdown of the Josephson dc current induced by pair condensate depletion. Moreover, we reveal a large and dominant anomalous contribution to resistive currents, which reaches its maximum at the lowest attained temperature, fostered by the tunnel coupling between the condensate and phononic Bogoliubov-Anderson excitations. Increasing the temperature, while the zeroing of supercurrents marks the transition to the normal phase, the conductance drops considerably but remains much larger than that of a normal, uncorrelated Fermi gas tunneling through the same junction. We attribute such enhanced transport to incoherent tunneling of sound modes, which remain weakly damped in the collisional hydrodynamic fluid of unpaired fermions at unitarity.

Strongly correlated superfluid order parameters from dc Josephson supercurrents.

The direct-current (dc) Josephson effect provides a phase-sensitive tool for investigating superfluid order parameters. We report on the observation of dc Josephson supercurrents in strongly interacting fermionic superfluids across a tunneling barrier in the absence of any applied potential difference. For sufficiently strong barriers, we observed a sinusoidal current-phase relation, in agreement with Josephson's seminal prediction. We mapped out the zero-resistance state and its breakdown as a function of junction parameters, extracting the Josephson critical current behavior. By comparing our results with an analytic model, we determined the pair condensate fraction throughout the Bardeen-Cooper-Schrieffer-Bose-Einstein condensation crossover. Our work suggests that coherent Josephson transport may be used to pin down superfluid order parameters in diverse atomic systems, even in the presence of strong correlations.

Role of tumour location and surgical extent on prognosis in T2 gallbladder cancer: an international multicentre study.

BACKGROUND: In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection. METHODS: Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted. RESULTS: Data from 937 patients were available for evaluation. The overall 5-year disease-free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5-year disease-free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5-year disease-free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five-year disease-free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic. CONCLUSION: Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.

ANTECEDENTES: En el cáncer de vesícula biliar, la ubicación del tumor subdivide el estadio T2 en tumores con invasión del lado peritoneal y del lado del hígado (T2a y T2b). Para los tumores que invaden el lado peritoneal (T2a) se sugiere que se puede obviar la resección hepática sin que ello comprometa el pronóstico. Sin embargo, este argumento no ha sido validado. El estudio tuvo como objetivo investigar el valor pronóstico de la localización del tumor en el cáncer de vesícula biliar T2 y establecer la extensión adecuada de la resección quirúrgica. MÉTODOS: Se recogieron los datos clínicos de pacientes que se sometieron a cirugía por cáncer de vesícula biliar en 14 hospitales de Corea, Japón, Chile y Estados Unidos. Se realizaron análisis de la supervivencia y de los factores de riesgo. RESULTADOS: Se dispuso de datos de 937 pacientes para ser evaluados. La tasa de supervivencia global libre de enfermedad a los 5 años fue del 70,6%, y las de T2a y T2b del 74,5% y 65,5% (P = 0,028). Con respecto a la resección hepática, la colecistectomía extendida presentó una tasa mejor de supervivencia libre de enfermedad a los 5 años que la colecistectomía simple (73,0% versus 61,5%, P = 0,012). La tasa de supervivencia libre de enfermedad a los 5 años fue marginalmente mejor para la colecistectomía extendida que para la colecistectomía simple tanto en T2a (76,5% versus 66,1%, P = 0,094) como en T2b (68,2% versus 56,2%, P = 0,084). Las tasas de supervivencia libre de enfermedad a los 5 años no fueron diferentes entre la resección hepática en cuña y la segmentectomía S4b+S5 (74,1% versus 71,5%, P = 0,720). En el análisis multivariable, los factores de riesgo independientes para la recidiva fueron la presencia de síntomas (cociente de riesgos instantáneos, hazard ratio, HR 1,52, P = 0,002), la resección R1 (HR 1,96, P = 0,004) y el estadio N1/N2 (N1 HR 3,40, P < 0,001; N2 HR 9,56, P < 0,001). El 70,8% de las recidivas eran metastásicas. CONCLUSIÓN: La localización del tumor no fue un factor pronóstico independiente en el cáncer de vesícula biliar T2. La colecistectomía extendida fue marginalmente superior que la colecistectomía simple. La cirugía radical debe incluir una resección hepática y una linfadenectomía adecuada.

Validation of a nomogram to predict the risk of cancer in patients with intraductal papillary mucinous neoplasm and main duct dilatation of 10 mm or less.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is premalignant pancreatic lesion. International guidelines offer limited predictors of individual risk. A nomogram to predict individual IPMN malignancy risk was released, with good diagnostic performance based on a large cohort of Asian patients with IPMN. The present study validated a nomogram to predict malignancy risk and invasiveness of IPMN using both Eastern and Western cohorts. METHODS: Clinicopathological and radiological data from patients who underwent pancreatic resection for IPMN at four centres each in Eastern and Western countries were collected. After excluding patients with missing data for at least one malignancy predictor in the nomogram (main pancreatic duct diameter, cyst size, presence of mural nodule, serum carcinoembryonic antigen and carbohydrate antigen (CA) 19-9 levels, and age). RESULTS: In total, data from 393 patients who fit the criteria were analysed, of whom 265 were from Eastern and 128 from Western institutions. Although mean age, sex, log value of serum CA19-9 level, tumour location, main duct diameter, cyst size and presence of mural nodule differed between the Korean/Japanese, Eastern and Western cohorts, rates of malignancy and invasive cancer did not differ significantly. Areas under the receiver operating characteristic (ROC) curve values for the nomogram predicting malignancy were 0·745 for Eastern, 0·856 for Western and 0·776 for combined cohorts; respective values for the nomogram predicting invasiveness were 0·736, 0·891 and 0·788. CONCLUSIONS: External validation of the nomogram showed good performance in predicting cancer in both Eastern and Western patients with IPMN lesions.

ANTECEDENTES: La neoplasia mucinosa papilar intraductal (intraductal papillary mucinous neoplasm, IPMN) es una lesión pancreática premaligna. Las guías internacionales incluyen un número limitado de factores predictivos de riesgo individual. Para predecir el riesgo individual de malignidad del IPMN se ha propuesto un nomograma con un buen rendimiento diagnóstico, basado en una gran cohorte de pacientes asiáticos con IPMN. Este estudio validó el nomograma para predecir el riesgo de cáncer y de invasión de la IPMN utilizando cohortes tanto orientales como occidentales. MÉTODOS: Se recogieron datos clínico-patológicos y radiológicos de pacientes en los que se realizó una resección de páncreas por IPMN en 4 centros en países orientales y en 4 centros de países occidentales. Se excluyeron los pacientes en los que en el nomograma faltaba ≥ 1 factor(es) predictivo(s) de malignidad (diámetro del conducto pancreático principal, tamaño del quiste, presencia de nódulo mural, niveles séricos de CEA y CA19-9, y edad). RESULTADOS: En total, se analizaron datos de 393 pacientes que cumplían con los criterios de inclusión, de los cuales 265 eran de centros orientales y 128 de centros occidentales. Aunque la edad media, el sexo, el valor logarítmico del nivel sérico de CA19-9, la localización del tumor, el diámetro del conducto principal, el tamaño del quiste y la presencia de un nódulo mural difirieron entre las cohortes de Corea/Japón y las cohortes oriental y occidental, las tasas de malignidad y de cáncer invasivo no fueron significativamente diferentes. Las áreas bajo la curva operativa del receptor (area under the receiver operating curve, AUC) que mostró el nomograma para predecir la malignidad fueron: cohorte oriental: 0,745; cohorte occidental: 0,856 y cohortes combinadas: 0,776; y para predecir la invasión tumoral fueron: cohorte oriental: 0,736; cohorte occidental: 0,891, y cohortes combinadas: 0,788. CONCLUSIÓN: La validación externa del nomograma mostró un buen rendimiento en la predicción de cáncer, tanto en pacientes orientales como occidentales con lesiones IPMN.

Isolation and initial characterization of new betanodaviruses in shellfish.

Betanodaviruses cause the disease viral nervous necrosis (VNN) in finfish. Using a novel approach with two consecutive PCRs, detection semi-nested two-step RT-PCR (DSN-2 RT-PCR) and discriminative multiplex two-step RT-PCR (DMT-2 RT-PCR), we have identified the presence of a new type of betanodavirus in shellfish and called it Korean shellfish nervous necrosis virus (KSNNV). Partial nucleotide sequences of the T4 region in RNA2 fragment of KSNNVs were 73%-75% homologous to those of other reported genotypes and formed a new cluster of betanodavirus in phylogenetic tree analysis. Successful isolation of KSNNV was achieved in two of six shellfish samples containing high concentrations of virus using the blind passage method, and the typical shapes of betanodavirus were confirmed in KSNNV-KOR1 by electron microscopy. In the experimental infection test, seven of 14 fish species showed susceptibility to KSNNV-KOR1 isolate but without clinical signs or death. Although the range of susceptible host species was not significantly different from the RGNNV type, the concentration of KSNNV in the brain of infected fish (102 -105 copies/mg brain) was much lower compared to that found in sevenband grouper (Epinephelus septemfasciatus Thunberg) sampled in the moribund stage with RGNNV infection (106 -107 copies/mg brain). However, histopathological analyses showed the presence of multiple vacuoles in brains of all KSNNV-infected fish at 14 days postinjection. In detection test, as a single or multiple type with the other genotype(s) (RGNNV or BFNNV), the prevalence of KSNNV was 8.4% and 8.7% in domestic (62 of 741 samples) and Chinese samples (12 of 138 samples), respectively, but not in finfish. We propose that KSNNVs obtained from shellfish be classified into a separate and new genotype of betanodavirus.

Blood pressure management and progression of chronic kidney disease in a canine remnant kidney model.

The canine remnant kidney model is fundamental to understanding the relationship between hypertension and chronic kidney disease (CKD). This study aimed to create a 1/16 remnant kidney model and to determine whether blood pressure (BP) control affects the progression of CKD. A group of dogs received BP treatment (group A) and another received BP treatment except for the first 2 weeks (group B). The remnant kidney model was induced using a two-step subtotal nephrectomy method; dogs received antihypertensive therapy. Systolic BP, blood urea nitrogen, serum creatinine, urinary protein, and creatinine levels were measured weekly. Kidney tissues were obtained at the conclusion of the study. Systolic BP was controlled to <160 mmHg in both groups for 18 weeks, except for the first 2 weeks in group B. Proteinuria was elevated after renal ligation in both groups, but gradually increased in group B and decreased in group A (p = 0.009). Blood urea nitrogen (p = 0.014) and creatinine (p = 0.020) levels were higher in group B than in group A. More histological damage was observed in group B than in group A. Induction of 1/16 nephrectomy successfully established CKD. Control of BP may be important to prevent or control the progression of CKD in dogs.

High prevalence of betanodavirus barfin flounder nervous necrosis virus as well as red-spotted grouper nervous necrosis virus genotype in shellfish.

Using two serially executed PCRs, the discriminative multiplex two-step RT-PCR (DMT-2 RT-PCR) following the detection seminested two-step RT-PCR (DSN-2 RT-PCR), we found a high frequency presence of BFNNV genotype as well as RGNNV in various domestic and imported shellfish. This was definitely different from the previous reports of outbreaks and asymptomatic infection only by the RGNNV genotype in cultured finfish in Korea. Cultivation of NNV entrapped in shellfish was performed successfully by a blind passage. Thus, in an attempt to elucidate the epidemiology of betanodavirus, experiments conducted on 969 shellfish samples concluded that (i) distribution of NNV genotype, especially BFNNV, in shellfish is clearly different from that found in finfish of the world; (ii) unlike RGNNV, which showed a high rate in summer, BFNNV showed no seasonal variation and this result suggests BFNNVs in the marine environment remain fairly constant throughout the year; and (iii) the entrapped virus in shellfish was alive and culturable in vitro. These results are the first report of high level prevalence of in vitro culturable NNV in shellfish, for both BFNNV and RGNNV, which may present a potential risk in transmitting nodaviruses to host species in a marine environment.

Photoassociation of Trilobite Rydberg Molecules via Resonant Spin-Orbit Coupling.

We report on a novel method for the photoassociation of strongly polar trilobite Rydberg molecules. This exotic ultralong-range dimer, consisting of a ground-state atom bound to the Rydberg electron via electron-neutral scattering, inherits its polar character from the admixture of high-angular-momentum electronic orbitals. The absence of low-L character hinders standard photoassociation techniques. Here, we show that for suitable principal quantum numbers the resonant coupling of the orbital motion with the nuclear spin of the perturber, mediated by electron-neutral scattering, hybridizes the trilobite molecular potential with the more conventional S-type molecular state. This provides a general path to associate trilobite molecules with large electric dipole moments, as demonstrated via high-resolution spectroscopy. We find a dipole moment of 135(45) D for the trilobite state. Our results are compared to theoretical predictions based on a Fermi model.

Influence of rabbit notochordal cells on symptomatic intervertebral disc degeneration: anti-angiogenic capacity on human endothelial cell proliferation under hypoxia.

OBJECTIVES: Symptomatic degenerative disc disease (DDD) is associated with neovascularization and nerve ingrowth into intervertebral discs (IVDs). Notochordal cells (NCs) are key cells that may lead to regeneration of IVDs. However, their activities under conditions of hypoxia, the real environment of IVD, are not well known. We hypothesized that NCs may inhibit neovascularization by interacting with endothelial cells (ECs) under hypoxia. DESIGN: Human IVDs were isolated and cultured to produce nucleus pulposus (NP) cell conditioned medium (NPCM). Immortalized human microvascular ECs were cultured in NPCM with notochordal cell-rich rabbit nucleus pulposus cells (rNC) under hypoxia. Vascular endothelial growth factor (VEGF), vascular cell adhesion molecule (VCAM), and interleukin-8 (IL-8) were analyzed by ELISA. Focal adhesion kinase (FAK), filamentous actin (F-actin), and platelet-derived growth factor (PDGF) were evaluated to investigate EC activity. Wound-healing migration assays were performed to examine EC migration. RESULTS: The VEGF level of EC cells cultured in NPCM was significantly higher under hypoxia compared to normoxia. VEGF expression was significantly decreased, and FAK, F-actin, PDGF expression were inhibited when ECs were cocultured with rNCs under hypoxia. ECs cocultured with rNC in NPCM showed significantly decreased migratory activity compared to those without rNC under hypoxia. CONCLUSIONS: The angiogenic capacity of ECs was significantly inhibited by NCs under hypoxia via a VEGF-related pathway. Our results suggest that NCs may play a key role in the development of IVDs by inhibiting vascular growth within the disc, and this may be a promising novel therapeutic strategy for targeting vascular ingrowth in symptomatic DDD.

Comparison of markers predicting litter size in different pig breeds.

To overcome the limitations of conventional analysis of male fertility in animals and humans, proteomic studies have been performed to develop fertility-related biomarkers for prognosis and diagnosis of male fertility. However, the studies were focused on specific species or breeds. Therefore, a study is required to validate whether fertility-related markers would apply to other breeds in pigs. In this study, previously developed fertility-related biomarkers from Landrace were validated to use for prognosis of male fertility in commercially available breeds. Expression level of eight biomarkers in non-capacitated and capacitated (C) spermatozoa from Yorkshire and Duroc boars was analyzed. And then, to explore the validity of these markers for prognosis of male fertility, i.e. litter size, artificial insemination was performed. Among them, RAB2A (NC) and UQCRC1 (NC) turned out to be highest efficient markers for Yorkshire. RAB2A (C) was most efficient marker for Duroc. Average litter size has increased as much as 1.41 live born after prediction using eight fertility-related biomarkers in Yorkshire. In addition, average 2.52 litter size was increased after prediction using eight fertility-related biomarkers in Duroc. Average litter sizes were especially highly increased after prediction of fertility using RAB2A (NC) in Yorkshire (1.57 piglets) and TPI (NC) in Duroc (3.14 piglets), respectively. As a result, all biomarkers were significantly correlated with litter size. However, overall accuracy to predict litter size in three breeds was different in response with each marker. Average litter size after artificial insemination was also significantly affected by marker selection. Therefore, this study suggests that developed fertility-related markers may be used for prognosis and diagnosis of male fertility irrespective of breed. However, selection of efficient markers for breeds should be considered to obtain more accurate and efficient outcomes.

Actin-related protein 2/3 complex-based actin polymerization is critical for male fertility.

The actin-related protein 2/3 (Arp2/3) complex is critical for regulation of actin polymerization, which is associated with sperm motility and capacitation status. However, the function of the Arp2/3 complex in male fertility has not yet been fully elucidated. Therefore, this study was designed to investigate the role of the Arp2/3 complex in different processes in spermatozoa and its consequences on fertilization and early embryonic development. In this in vitro study, mouse spermatozoa were incubated with different concentrations (10, 100, and 500 µm) of CK-636, an Arp2/3 complex antagonist. Our results demonstrated that inhibition of the Arp2/3 complex by high concentrations (100 and 500 µm) of CK-636 induced hyper-activated motility and acrosomal reaction, whereas intracellular calcium and tyrosine phosphorylation levels in spermatozoa were inhibited. Moreover, exposure of spermatozoa to the highest concentration of CK-636 reduced fertilization and embryo development. Interestingly, fertilization was significantly increased after treatment with 100 µm CK-636, whereas embryonic development was significantly decreased. Therefore, we conclude that the Arp2/3 complex plays a decisive role in regulation of sperm function and male fertility via actin polymerization. We anticipate that the Arp2/3 complex may have clinical application as marker for male fertility and male contraceptive targeting.

Effects of Supplemental Beta-mannanase on Digestible Energy and Metabolizable Energy Contents of Copra Expellers and Palm Kernel Expellers Fed to Pigs.

The purpose of this study was to determine the effect of ß-mannanase supplementation on digestible energy (DE) and metabolizable energy (ME) contents of copra expellers (CE) and palm kernel expellers (PKE) fed to pigs. Six barrows with an initial body weight of 38.0 kg (standard deviation = 1.5) were randomly allotted to a 6×6 Latin square design with 6 dietary treatments and 6 periods. Six experimental diets were prepared in a 3×2 factorial treatment arrangement with 3 diets of a corn-soybean meal-based diet, a CE 30% diet, and a PKE 30% diet and with 2 concentrations of supplemental ß-mannanase at 0 or 2,400 U/kg. All diets had the same proportion of corn:soybean meal ratio at 2.88:1. The marker-to-marker procedure was used for fecal and urine collection with 4-d adaptation and 5-d collection periods. No interactive effects were observed between diet and ß-mannanase on energy digestibility and DE and ME contents of experimental diets. However, diets containing CE or PKE had less (p<0.05) DE and ME contents compared with the corn-soybean meal-based diet. The DE and ME contents in CE and PKE were not affected by supplemental ß-mannanase. Taken together, we failed to find the effect of ß-mannanase supplementation on energy utilization in CE and PKE fed to pigs.

Improving litter size by boar spermatozoa: application of combined H33258/CTC staining in field trial with artificial insemination.

Conventional semen analysis offers basic information on infertility; however, its clinical value in predicting fertility status is unclear. To establish an accurate diagnosis of male fertility, semen analysis under capacitation condition is necessary because only capacitated spermatozoa are capable of fertilizing oocytes. The objective of this study was to verify male fertility based on conventional semen analysis before and after capacitation, including the assessment of motility (%), motion kinematics, and capacitation status of spermatozoa. A computer-assisted sperm analysis system and chlortetracycline staining were applied to evaluate the motility parameters and capacitation status, respectively. To enable efficacy of the two methods for predicting fertility, correlation analysis was performed with the historic litter size. Our results showed that sperm motility (%), motion kinematics, and their variations before and after capacitation represented a statistical non-significant correlation with litter size. Litter size showed significant correlation with acrosome reaction (AR) after capacitation (r = 0.375), as well as differences (Δ) in AR (r = 0.333) and capacitated (B) pattern (r = -0.447) before and after capacitation. The overall accuracy of the assay for predicting litter sizes using the AR and differences (Δ) in the AR and B pattern was 70%. On the basis of these results, we propose that capacitation status of spermatozoa is a more reliable indicator for evaluating male fertility status compared to motility parameters. Therefore, we suggest that analysis of capacitation status in company with conventional semen analysis may accept to evaluate more accurate diagnosis or prognosis of male fertility.

Sodium nitroprusside suppresses male fertility in vitro.

Sodium nitroprusside is a nitric oxide donor involved in the regulation of the motility, hyperactivation, capacitation, and acrosome reaction (AR) of spermatozoa. However, the molecular mechanism underlying this regulation has not yet been elucidated. Therefore, this study was designed to evaluate the molecular basis for the effects of sodium nitroprusside on different processes in spermatozoa and its consequences on subsequent oocyte fertilization and embryo development. In this in vitro study, mouse spermatozoa were incubated with various concentrations of sodium nitroprusside (1, 10, and 100 µM) for 90 min. Our results showed that sodium nitroprusside inhibited sperm motility and motion kinematics in a dose-dependent manner by significantly enhancing intracellular iron and reactive oxygen species (ROS), and decreasing Ca(2+), and adenosine triphosphate levels in spermatozoa. Moreover, short-term exposure of spermatozoa to sodium nitroprusside increased the tyrosine phosphorylation of sperm proteins involved in PKA-dependent regulation of intracellular calcium levels, which induced a robust AR. Finally, sodium nitroprusside significantly decreased the rates of fertilization and blastocyst formation during embryo development. Based on these results, we propose that sodium nitroprusside increases ROS production and precocious AR may alter overall sperm physiology, leading to poor fertilization and compromised embryonic development.

Color stability of white organic light emitting devices with a color conversion layer utilizing CdSe/ZnS quantum dots and phosphors dispersed in polymethylmethacrylate.

White organic light-emitting devices (WOLEDs) were fabricated by combining a blue emitting organic light-emitting devices (OLEDs) and a color conversion layer made of yttrium aluminum garnet phosphors and CdSe/ZnS quantum dots (QDs) embedded into polymethylmethacrylate. When the ratio of phosphors and QDs changed, a good color balance was achieved at a ratio of 1:5, and the maximum luminance of 18.21 cd/m2 was obtained. As the applied voltage varied from 12 to 16 V, Commission Internationale de l'Eclairage coordinates shifted only slightly from (0.32, 0.34) to (0.30, 0.33), indicating a good color stability.

Effects of pancreatectomy on nutritional state, pancreatic function and quality of life.

BACKGROUND: There are concerns about the extent of impaired endocrine and exocrine pancreatic function and poor quality of life (QoL) after pancreatectomy, but there is little information from large prospective follow-up studies. METHODS: Consecutive patients undergoing pancreaticoduodenectomy or distal pancreatectomy between 2007 and 2011 were included. Relative bodyweight (RBW), triceps skinfold thickness (TSFT), serum protein, albumin, transferrin, fasting blood glucose, postprandial 2-h glucose (PP2), glycosylated haemoglobin A1c and stool elastase measurements, and European Organization for Research and Treatment of Cancer QLQ-C30 questionnaires were collected serially for 1 year. RESULTS: Some 136 patients undergoing pancreatic resection completed the study. RBW and TSFT recovered to over 90 per cent of the preoperative value by 12 months, whereas transferrin, albumin and protein had returned to preoperative levels by 3 months. Diabetes mellitus, impaired fasting glucose or raised PP2 was present in 42 of 76 patients at 6 months and 36 of 76 at 12 months. Although steatorrhoea and diarrhoea had mainly resolved by 3 months, stool elastase level decreased after operation and showed no recovery. Nutritional status, pancreatic endocrine function and QoL returned to preoperative levels in 63 (46·3 per cent), 72 (52·9 per cent) and 77 (56·6 per cent) of 136 patients within 6 months of pancreatectomy. Multivariable analysis revealed that age 60 years or more, operation type, chronic pancreatitis and malignant disease had a significant impact on nutritional index, pancreatic function and QoL. CONCLUSION: About half of all patients can expect recovery from pancreatectomy after 6 months, but those with risk factors need more careful follow-up and supportive management.

Changing trend in bile microbiology and antibiotic susceptibilities: over 12 years of experience.

PURPOSE: Rapidly changing medical environments may have changed the microbiology of infected bile. The aim of our study was to identify the changing trends in microorganisms in biliary infections and examine their susceptibilities against currently recommended antibiotics. METHODS: Bile cultures taken between 1998 and 2010 at Seoul National University Hospital, a tertiary medical center, were retrospectively reviewed. From 1,403 patients, 3,425 microorganisms were isolated from 2,217 cultures. The cultures were then tested to determine the types of microorganisms and their antibiotic susceptibility. RESULTS: The five most frequently isolated microorganisms were Enterococcus (22.7 %) followed by Escherichia (13.2 %), Pseudomonas (10.9 %), Klebsiella (10.3 %), and Enterobacter (7.2 %). The trend in annual incidence indicated a growing emergence of Enterococcus (P < 0.001). Among Enterococcus, E. faecium acquired a dominant position (50.6 %), showing an increasing trend over the study period (P = 0.026). The incidence of vancomycin-resistant Enterococcus also showed an increasing trend (P < 0.001). Many of the commonly used antibiotics provided inadequate coverage for the more frequently encountered microorganisms. Multiple regression revealed that benign causes of obstruction and non-operative treatment harbor an increased risk for enterococcal growth (P = 0.001 and P = 0.027, respectively). CONCLUSIONS: In contrast to earlier reports, we found that Enterococcus has emerged as the most frequently isolated microorganism from bile. The importance of enterococcal infection should be recognized, and currently recommended antibiotics need to be re-evaluated since in our bile cultures most provided inadequate coverage for the more frequently encountered microorganisms. The changes in the trends of microorganisms isolated from bile should be considered in cases where patients present with biliary obstruction.