Assessment of the APCC Coupled MME Suite in Predicting the Distinctive Climate Impacts of Two Flavors of ENSO during Boreal Winter

Forecast skill of the APEC Climate Center (APCC) Multi-Model Ensemble (MME) seasonal forecast system in predicting two main types of El Nino-Southern Oscillation (ENSO), namely canonical (or cold tongue) and Modoki ENSO, and their regional climate impacts is assessed for boreal winter. The APCC MME is constructed by simple composite of ensemble forecasts from five independent coupled ocean-atmosphere climate models. Based on a hindcast set targeting boreal winter prediction for the period 19822004, we show that the MME can predict and discern the important differences in the patterns of tropical Pacific sea surface temperature anomaly between the canonical and Modoki ENSO one and four month ahead. Importantly, the four month lead MME beats the persistent forecast. The MME reasonably predicts the distinct impacts of the canonical ENSO, including the strong winter monsoon rainfall over East Asia, the below normal rainfall and above normal temperature over Australia, the anomalously wet conditions across the south and cold conditions over the whole area of USA, and the anomalously dry conditions over South America. However, there are some limitations in capturing its regional impacts, especially, over Australasia and tropical South America at a lead time of one and four months. Nonetheless, forecast skills for rainfall and temperature over East Asia and North America during ENSO Modoki are comparable to or slightly higher than those during canonical ENSO events

Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation

Background/AimsThe dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT).MethodsTwo sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT.ResultsIn the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively.ConclusionsA reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT

JAZF1 heterozygous knockout mice show altered adipose development and metabolism

Background: Juxtaposed with another zinc finger protein 1 (JAZF1) is associated with metabolic disorders, including type 2 diabetes mellitus (T2DM). Several studies showed that JAZF1 and body fat mass are closely related. We attempted to elucidate the JAZF1 functions on adipose development and related metabolism using in vitro and in vivo models. Results: The JAZF1 expression was precisely regulated during adipocyte differentiation of 3T3-L1 preadipocyte and mouse embryonic fibroblasts (MEFs). Homozygous JAZF1 deletion (JAZF1-KO) resulted in impaired adipocyte differentiation in MEF. The JAZF1 role in adipocyte differentiation was demonstrated by the regulation of PPARγ—a key regulator of adipocyte differentiation. Heterozygous JAZF1 deletion (JAZF1-Het) mice fed a normal diet (ND) or a high-fat diet (HFD) had less adipose tissue mass and impaired glucose homeostasis than the control (JAZF1-Cont) mice. However, other metabolic organs, such as brown adipose tissue and liver, were negligible effect on JAZF1 deficiency. Conclusion: Our findings emphasized the JAZF1 role in adipocyte differentiation and related metabolism through the heterozygous knockout mice. This study provides new insights into the JAZF1 function in adipose development and metabolism, informing strategies for treating obesity and related metabolic disorders. © 2021, The Author(s).1

Bone Morphogenetic Protein Signaling: Implications in Urology

The bone morphogenetic proteins (BMPs), as members of the transforming growth factor-β (TGF-β) superfamily, not only control bone formation, but also regulate multiple key steps during embryonic development and differentiation. Furthermore, BMPs play critical roles in maintaining the homeostasis of the cardiovascular, pulmonary, reproductive, urogenital, and nervous systems in adult life. Like all members of the TGF-β superfamily, BMP signaling is mediated through a heteromeric complex of type I and type II transmembrane serine/threonine kinase receptors. The subsequent signal transduction cascade includes either the canonical Smad-dependent or non-canonical Smad-independent pathways. Reflecting the critical function of BMPs, BMP signaling is tightly regulated at multiple steps by various mechanisms including extracellular endogenous antagonists, neutralizing antibodies/extracellular soluble receptor domains, small molecule inhibitors, cytoplasmic inhibitory Smads, and transcriptional co-repressors. Recently, dorsomorphin, the first small molecule inhibitor of BMP signaling, was identified and suggested as a useful tool for dissecting the mechanisms of signaling pathways and for developing novel therapeutics for diverse human diseases that are related to the BMP signaling pathways. In this article, we discuss various mechanisms involved in regulating BMP signaling pathways and their implications for urology

Indirect CT Venography at 80 kVp with Sinogram-Affirmed Iterative Reconstruction Compared to 120 kVp with Filtered Back Projection: Assessment of Image Quality and Radiation Dose.

OBJECTIVE:To evaluate the image quality and radiation dose of indirect computed tomographic venography (CTV) using 80 kVp with sinogram-affirmed iterative reconstruction (SAFIRE) and 120 kVp with filtered back projection (FBP). MATERIALS AND METHODS:This retrospective study was approved by our institution and informed consent was waived. Sixty-one consecutive patients (M: F = 27: 34, mean age 60 ± 16, mean BMI 23.6 ± 3.6 kg/m2) underwent pelvic and lower extremity CTVs [group A (n = 31, 120 kVp, reconstructed with FBP) vs. group B (n = 30, 80 kVp, reconstructed with SAFIRE)]. The vascular enhancement, image noise, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were compared. Subjective image analysis for image quality and noise was performed by two radiologists. Radiation dose was compared between the two groups. RESULTS:Compared with group A, higher mean vascular enhancement was observed in the group B (group A vs. B, 118.8 ± 15.7 HU vs. 178.6 ± 39.6 HU, p 0.05). The subjective image noise was higher in the group B (p = 0.036 in reader 1, p = 0.005 in reader 2). The inter-observer reliability for assessing subjective image quality was good (ICC 0.746~0.784, p < 0.001). The mean CT dose index volume (CTDIvol) and mean dose length product (DLP) were significantly lower in group B than group A [CTDIvol, 6.4 ± 1.3 vs. 2.2 ± 2.2 mGy (p < 0.001); DLP, 499.1 ± 116.0 vs. 133.1 ± 45.7 mGy × cm (p < 0.001)]. CONCLUSIONS:CTV using 80 kVp combined with SAFIRE provides lower radiation dose and improved CNR compared to CTV using 120 kVp with FBP

Diagnostic Accuracy and Complication of Computed Tomography (CT)-Guided Percutaneous Transthoracic Lung Biopsy in Patients 80 Years and Older

This research evaluated the diagnostic accuracy and complication rate of computed tomography (CT)-guided percutaneous transthoracic lung biopsy (PTNB) in patients 80 years and older. The study sought to identify risk factors for diagnostic failures or complications of PTNBs. We examined 247 CT-guided PTNBs performed from January 2017 through December 2020, noting patient demographics, lesion or procedure types, pathology reports, and other procedure-related complications. Study groups were divided into two: one with patients aged 80 years and older (Group 1) and the other with patients aged 60 to 80 years (Group 2). The research first determined each groups’ diagnostic accuracy, sensitivity, specificity, diagnostic failure rate, and complication rate and then evaluated the risk factors for diagnostic failures and complications. The diagnostic accuracy, sensitivity, specificity, and diagnostic failure rates were 95.6%, 94.9%, 100%, and 18.9%, respectively, in Group 1. The overall and major complication rates in Group 1 were 29.6% and 3.7%, respectively. Lesion size was the only risk factor for diagnostic failure (adjusted odds ratio [OR], 0.46; 95% confidence interval [CI], 0.24–0.90). There was no significant risk factor for complications in Group 1. CT-guided PTNBs in patients 80 years and older indicate comparable diagnostic accuracy and complication rates

Axial CTV images obtained using 120 kVp and FBP in a 49-year-old woman with BMI 23.9.

<p>Attenuation value, vein-to-muscle contrast-to-noise ratio and signal-to-noise ratio in this patient were 134.7 HU, 7.2, and 8.2 in the IVC (a), 147.3 HU, 8.6, and 16.6 in the CFV (b), and 121.8 HU, 5.9 and 10.4 in the PV (c). Attenuation values of subcutaneous fat and muscle at the mid-thigh level were also measured using circular ROIs (d). The image quality was subjectively classified as score 4 (good) for the overall image quality and score 1 (optimal) for the image noise by the two readers. *CTV computed tomographic venography, FBP filtered back projection, BMI body mass index, HU Hounsfield unit, IVC inferior vena cava, CFV common femoral vein, PV popliteal vein, ROI region of interest.</p

Axial CTV images obtained using 80 kVp and SAFIRE in a 75-year-old woman with BMI 23.2.

<p>Attenuation value, vein-to-muscle contrast-to-noise ratio and signal-to-noise ratio in this patient were 237.5 HU, 12.6, and 9.3 in the IVC (a), 211.4 HU, 10.6, and 16.0 in the CFV (b), and 192.4 HU, 9.2 and 11.7 in the PV (c). Attenuation values of subcutaneous fat and muscle at the mid-thigh level were also measured using circular ROIs (d). Intraluminal filling defect (arrow) was detected in the right popliteal vein, which was diagnosed as DVT. The overall image quality scores and image noise scores were 5 (excellent) and 1 (optimal) for reader 1 and 4 (good) and 1 (optimal) for reader 2. *CTV computed tomographic venography, SAFIRE sinogram-affirmed iterative reconstruction, BMI body mass index, HU Hounsfield unit, IVC inferior vena cava, CFV common femoral vein, PV popliteal vein, ROI region of interest.</p