Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis

Yu, K&#x2010,H.,Hong, K&#x2010,S.,Lee, B&#x2010,C.,Oh, M&#x2010,S.,Cho, Y&#x2010,J.,Koo, J&#x2010,S.,Park, J&#x2010,M.,Bae, H&#x2010,J.,Han, M&#x2010,K.,Ju, Y&#x2010,S.,Kang, D&#x2010,W.,Appelros, P. Blackwell Publishing Ltd 2011 Acta neurologica Scandinavica Vol.123 No.5

<P>Yu K‐H, Hong K‐S, Lee B‐C, Oh M‐S, Cho Y‐J, Koo J‐S, Park J‐M, Bae H‐J, Han M‐K, Ju Y‐S, Kang D‐W, Appelros P, Norrving B, Terent A. Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis. 
Acta Neurol Scand: 2011: 123: 325–331. 
© 2010 John Wiley & Sons A/S.</P><P><B>Background – </B> It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case‐fatality between two PSM cohorts of Sweden and Korea.</P><P><B>Methods – </B> Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one‐to‐one matching based on propensity scores of each patient.</P><P><B>Results – </B> After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90‐day case‐fatality was identical 6.2% (HR 0.997, 95%CI 0.905–1.099) in Sweden and Korea.</P><P><B>Conclusions – </B> No difference is found in the 90‐day case‐fatality in propensity score‐matched Swedish and Korean patients with ischemic stroke.</P>

OGLE‐2009‐BLG‐023/MOA‐2009‐BLG‐028: characterization of a binary microlensing event based on survey data

Hwang, K.&#x2010,H.,Han, C.,Udalski, A.,Sumi, T.,Gould, A.,Jaroszy&#x144,ski, M.,Kubiak, M.,Szyma&#x144,ski, M. K.,Pietrzy&#x144,ski, G.,Soszy&#x144,ski, I.,Szewczyk, O.,Ulaczyk, K.,Wyrzykowski, &#x13 Blackwell Publishing Ltd 2011 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.413 No.2

<P><B>ABSTRACT</B></P><P>We report the result of the analysis of the light curve of a caustic‐crossing binary‐lens microlensing event OGLE‐2009‐BLG‐023/MOA‐2009‐BLG‐028. Even though the event was observed solely by survey experiments, we could uniquely determine the mass of the lens and distance to it by simultaneously measuring the Einstein radius and lens parallax. From this, we find that the lens system is composed of M‐type dwarfs with masses (0.50 ± 0.07) and (0.15 ± 0.02) M<SUB>⊙</SUB> located in the Galactic disc with a distance of ∼1.8 kpc toward the Galactic bulge direction. The event demonstrates that physical lens parameters of binary‐lens events can be routinely determined from future high‐cadence lensing surveys and thus microlensing can provide a new way to study Galactic binaries.</P>

Long‐term efficacy and safety of bosutinib in patients with advanced leukemia following resistance/intolerance to imatinib and other tyrosine kinase inhibitors

Gambacorti&#x2010,Passerini, Carlo,Kantarjian, Hagop M.,Kim, Dong&#x2010,Wook,Khoury, Hanna J.,Turkina, Anna G.,Brü,mmendorf, Tim H.,Matczak, Ewa,Bardy&#x2010,Bouxin, Nathalie,Shapiro, Mark,Turnbu John Wiley and Sons Inc. 2015 American journal of hematology Vol.90 No.9

<P>Long‐term efficacy and safety of bosutinib (≥4 years follow‐up from last enrolled patient) were evaluated in an ongoing phase 1/2 study in the advanced leukemia cohort with prior treatment failure (accelerated‐phase [AP, <I>n =</I> 79] chronic myeloid leukemia [CML], blast‐phase [BP, <I>n =</I> 64] CML, acute lymphoblastic leukemia [ALL, <I>n =</I> 24]). Fourteen AP, 2 BP, and 1 ALL patient remained on bosutinib at 4 years (vs. 38, 8, 1 at 1 year); median (range) treatment durations: 10.2 (0.1–88.6), 2.8 (0.03–55.9), 0.97 (0.3–89.2) months. Among AP and BP patients, 57% and 28% newly attained or maintained baseline overall hematologic response (OHR); 40% and 37% attained/maintained major cytogenetic response (MCyR) by 4 years (most by 12 months). In responders at 1 versus 4 years, Kaplan‐Meier (KM) probabilities of maintaining OHR were 78% versus 49% (AP) and 28% versus 19% (BP); KM probabilities of maintaining MCyR were 65% versus 49% (AP) and 21% versus 21% (BP). Most common AEs (AP, BP) were gastrointestinal (96%; 83%), primarily diarrhea (85%; 64%), which was typically low grade (maximum grade 1/2: 81%; 59%) and transient; no patient discontinued due to diarrhea. Serious AEs occurred in 44 (56%) AP and 37 (58%) BP patients, most commonly pneumonia (<I>n =</I> 9) for AP and pyrexia (<I>n =</I> 6) for BP; 11 and 13 died within 30 days of last dose (2 considered bosutinib‐related [AP] per investigator). Responses were durable in ∼50% AP responders at 4 years (∼25% BP patients responded at year 1, suggesting possible bridge‐to‐transplant role in BP patients); toxicity was manageable.Am. J. Hematol. 90:755–768, 2015. © 2015 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.</P>

Permanent Chemotherapy‐Induced Alopecia in Patients with Breast Cancer: A 3‐Year Prospective Cohort Study

Kang, Danbee,Kim, Im&#x2010,Ryung,Choi, Eun&#x2010,Kyung,Im, Young Hyuck,Park, Yeon Hee,Ahn, Jin Seok,Lee, Jeong Eon,Nam, Seok Jin,Lee, Hae Kwang,Park, Ji&#x2010,Hye,Lee, Dong&#x2010,Youn,Lacouture, M AlphaMed Press 2019 The oncologist Vol.24 No.3

<P>Chemotherapy‐induced alopecia is (CIA) considered temporary; however, some patients report persistent alopecia several years after chemotherapy. Long‐term prospective data on the incidence and impact of permanent CIA is scarce. This article reports the results of a study conducted to estimate the long‐term incidence of persistent CIA in a cohort of breast cancer patients with measurements of hair volume and density before and after chemotherapy.</P><P><B>Background.</B></P><P>Although chemotherapy‐induced alopecia (CIA) is considered temporary, some patients report persistent alopecia several years after chemotherapy. There is, however, a paucity of long‐term prospective data on the incidence and impact of permanent CIA (PCIA). The objective of our study was to estimate the long‐term incidence of PCIA in a cohort of patients with breast cancer whose hair volume and density were measured prior to chemotherapy and who were followed for 3 years after chemotherapy.</P><P><B>Materials and Methods.</B></P><P>Prospective cohort study of consecutive patients ≥18 years of age with postoperative diagnosis of stage I–III breast cancer expected to receive adjuvant chemotherapy at the outpatient breast cancer clinic at the Samsung Medical Center in Seoul, Korea, from February 2012 to July 2013 (<I>n</I> = 61). Objective hair density and thickness were measured using a noninvasive bioengineering device.</P><P><B>Results.</B></P><P>The proportion of participants who had PCIA at 6 months and 3 years was 39.5% and 42.3%, respectively. PCIA was characterized in most patients by incomplete hair regrowth. Patients who received a taxane‐based regimen were more likely to experience PCIA compared with patients with other types of chemotherapy. At a 3‐year follow‐up, hair thinning was the most common problem reported by study participants (75.0%), followed by reduced hair volume (53.9%), hair loss (34.6%), and gray hair (34.6%).</P><P><B>Conclusion.</B></P><P>PCIA is a common adverse event of breast cancer adjuvant cytotoxic chemotherapy. Clinicians should be aware of this distressing adverse event and develop supportive care strategies to counsel patients and minimize its impact on quality of life.</P><P><B>Implications for Practice.</B></P><P>Knowledge of permanent chemotherapy‐induced alopecia, an under‐reported adverse event, should lead to optimized pretherapy counseling, anticipatory coping techniques, and potential therapeutic strategies for this sequela of treatment.</P>

Upstream kinases of plant Sn RK s are involved in salt stress tolerance

Barajas&#x2010,Lopez, Juan de Dios,Moreno, Jose Ramon,Gamez&#x2010,Arjona, Francisco M.,Pardo, Jose M.,Punkkinen, Matleena,Zhu, Jian&#x2010,Kang,Quintero, Francisco J.,Fujii, Hiroaki John Wiley and Sons Inc. 2018 The Plant journal Vol.93 No.1

<▼1><P><B>Summary</B></P><P>Sucrose non‐fermenting 1‐related protein kinases (SnRKs) are important for plant growth and stress responses. This family has three clades: SnRK1, SnRK2 and SnRK3. Although plant SnRKs are thought to be activated by upstream kinases, the overall mechanism remains obscure. Geminivirus Rep‐Interacting Kinase (GRIK)1 and GRIK2 phosphorylate SnRK1s, which are involved in sugar/energy sensing, and the <I>grik1‐1 grik2‐1</I> double mutant shows growth retardation under regular growth conditions. In this study, we established another Arabidopsis mutant line harbouring a different allele of gene <I>GRIK1</I> (<I>grik1‐2 grik2‐1</I>) that grows similarly to the wild‐type, enabling us to evaluate the function of GRIKs under stress conditions. In the <I>grik1‐2 grik2‐1</I> double mutant, phosphorylation of SnRK1.1 was reduced, but not eliminated, suggesting that the <I>grik1‐2</I> mutation is a weak allele. In addition to high sensitivity to glucose, the <I>grik1‐2 grik2‐1</I> mutant was sensitive to high salt, indicating that GRIKs are also involved in salinity signalling pathways. Salt Overly Sensitive (SOS)2, a member of the SnRK3 subfamily, is a critical mediator of the response to salinity. GRIK1 phosphorylated SOS2 <I>in vitro</I>, resulting in elevated kinase activity of SOS2. The salt tolerance of <I>sos2</I> was restored to normal levels by wild‐type SOS2, but not by a mutated form of SOS2 lacking the T168 residue phosphorylated by GRIK1. Activation of SOS2 by GRIK1 was also demonstrated in a reconstituted system in yeast. Our results indicate that GRIKs phosphorylate and activate SnRK1 and other members of the SnRK3 family, and that they play important roles in multiple signalling pathways <I>in vivo</I>.</P></▼1><▼2><P><B>Significance Statement</B></P><P>Since plants face diverse, often coincidental stresses throughout their lifetime, they have to integrate multiple signals to organize growth, development and stress responses. This work shows that GRIKs, which are essential players in sugar signalling pathway as upstream kinases of SnRK1s, also work in salt tolerance of Arabidopsis and identified SOS2, a SnRK3, as a potential substrate of GRIKs in the salinity signalling pathway.</P></▼2>

Serine palmitoyltransferase inhibitor myriocin induces growth inhibition of B16F10 melanoma cells through G₂/M phase arrest

Lee, Y.&#x2010,S.,Choi, K.&#x2010,M.,Choi, M.&#x2010,H.,Ji, S.&#x2010,Y.,Lee, S.,Sin, D.&#x2010,M.,Oh, K.&#x2010,W.,Lee, Y.&#x2010,M.,Hong, J.&#x2010,T.,Yun, Y.&#x2010,P.,Yoo, H.&#x2010,S. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.4

<P><B>Abstract</B></P><P><B>Objectives: </B> Melanoma is the most aggressive form of skin cancer, and it resists chemotherapy. Candidate drugs for effective anti‐cancer treatment have been sought from natural resources. Here, we have investigated anti‐proliferative activity of myriocin, serine palmitoyltransferase inhibitor, in the <I>de novo</I> sphingolipid pathway, and its mechanism in B16F10 melanoma cells.</P><P><B>Material and methods: </B> We assessed cell population growth by measuring cell numbers, DNA synthesis, cell cycle progression, and expression of cell cycle regulatory proteins. Ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate levels were analysed by HPLC.</P><P><B>Results: </B> Myriocin inhibited proliferation of melanoma cells and induced cell cycle arrest in the G<SUB>2</SUB>/M phase. Expressions of cdc25C, cyclin B1 and cdc2 were decreased in the cells after exposure to myriocin, while expression of p53 and p21<SUP>waf1/cip1</SUP> was increased. Levels of ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate in myriocin‐treated cells after 24 h were reduced by approximately 86%, 57%, 75% and 38%, respectively, compared to levels in control cells.</P><P><B>Conclusions: </B> Our results suggest that inhibition of sphingolipid synthesis by myriocin in melanoma cells may inhibit expression of cdc25C or activate expression of p53 and p21<SUP>waf1/cip1</SUP>, followed by inhibition of cyclin B1 and cdc2, resulting in G<SUB>2</SUB>/M arrest of the cell cycle and cell population growth inhibition. Thus, modulation of sphingolipid metabolism by myriocin may be a potential target of mechanism‐based therapy for this type of skin cancer.</P>

Epidermal regeneration by <i>ent</i>‐16α, 17‐dihydroxy‐kauran‐19‐oic acid isolated from <i>Siegesbeckia pubescens</i>

Sung, S.&#x2010,H.,Park, S.&#x2010,H.,Song, S.&#x2010,Y.,Lee, S.&#x2010,J.,Lee, H.&#x2010,W.,Kim, S.&#x2010,H.,A Lee, M.,Yoon, I.&#x2010,S.,Kim, D.&#x2010,D.,Kang, S.,Sung, J.&#x2010,H. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.6

<P><B>Abstract</B></P><P><B>Objectives: </B> Keratinocyte stem/progenitor cells (KSCs) are known to regenerate epidermal tissue which they perform through to their great regenerative capacity.</P><P><B>Materials and methods: </B> Because stimulation of resident KSCs may regenerate epidermal tissue, we devised a strategy to find an appropriate KSC activator from natural products and to develop it as a skin‐rejuvenating agent.</P><P><B>Results: </B> <I>Ent</I>‐16α, 17‐dihydroxy‐kauran‐19‐oic acid (DHK) isolated from <I>Siegesbeckia pubescens</I> exhibited a KSC‐stimulating effect during screening of natural products. DHK increased proliferation and migration of KSCs using the Akt/ERK pathway. We further examined the mechanism of KSC stimulation and found that phosphorylation of Y1068 epithelial growth factor receptor (EGFR) was significantly increased. Functional inhibition of EGFR using neutralizing antibody and a chemical inhibitor, AG1478, attenuated DHK‐induced KSC stimulation. In a 3D culture model of KSCs, DHK treatment significantly induced establishment of fully stratified epidermis and increased numbers of p63‐positive cells. Likewise, DHK treatment significantly accelerated healing of epidermal wounds created by laser and dermatome, and increased p63‐positive cells, in animal models.</P><P><B>Conclusion: </B> Collectively, these results indicate that DHK regenerates epidermal tissue mainly through EGFR phosphorylation. As DHK has diverse advantages over recombinant growth factors for commercialization (that is long‐term stability and skin permeability), DHK might be applied to wound‐healing agents and to a basic materials used in cosmetics.</P>

Serum Adipokine Concentrations in Dogs with Naturally Occurring Pituitary‐Dependent Hyperadrenocorticism

Cho, K.&#x2010,D.,Paek, J.,Kang, J.&#x2010,H.,Chang, D.,Na, K.&#x2010,J.,Yang, M.&#x2010,P. John Wiley and Sons Inc. 2014 Journal of veterinary internal medicine Vol.28 No.2

<P><B>Background</B></P><P>An excess of intra‐abdominal fat is observed frequently in dogs with hyperadrenocorticism (HAC). Adipokine dysregulation is a possible cause of complications related to visceral obesity, but little information is available on adipokine in dogs with naturally occurring HAC.</P><P><B>Objectives</B></P><P>To examine the differences in the circulating adipokines concentrations in overweight dogs with and without pituitary‐dependent HAC (PDH).</P><P><B>Animals</B></P><P>Thirty healthy dogs and 15 client‐owned dogs with PDH.</P><P><B>Methods</B></P><P>Case–controlled observational study, which enrolled 15 overweight dogs diagnosed with PDH and 30 otherwise healthy dogs of similar body condition score. Nine of 15 dogs with PDH were treated with low‐dose trilostane twice daily and reassessed after treatment.</P><P><B>Results</B></P><P>The serum leptin (<I>P</I> < .0001) and insulin (<I>P</I> < .0001) concentrations were significantly higher in the PDH group (leptin, 22.8 ± 8.8 [mean ± SD]; insulin, 9.1 ± 6.1) than the healthy group (leptin, 4.9 ± 3.7; insulin, 1.9 ± 0.9). However, there were no significant differences in the adiponectin, resistin, tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐10, and IL‐18 levels between the 2 groups. In the PDH group, the serum cortisol concentrations had a linear association with the leptin concentrations, and there were significant decreases in the leptin (<I>P</I> = .0039) and insulin (<I>P</I> = .0039) levels after trilostane treatment. However, the leptin and insulin levels remained higher after trilostane treatment than in healthy control dogs with similar body condition score.</P><P><B>Conclusions and Clinical Importance</B></P><P>Hypercortisolemia in dogs with PDH might upregulate the circulating leptin levels. However, a large population‐based study will be necessary to determine whether the upregulation of leptin is involved directly with the complications caused by HAC.</P>

Wound healing/regeneration using recombinant human growth/differentiation factor‐5 in an injectable poly‐lactide‐co‐glycolide‐acid composite carrier and a one‐wall intra‐bony defect model in dogs

Min, Cheon&#x2010,Ki,Wikesjö,, Ulf M. E.,Park, Jung&#x2010,Chul,Chae, Gyung&#x2010,Joon,Pippig, Susanne D.,Bastone, Patrizia,Kim, Chang&#x2010,Sung,Kim, Chong&#x2010,Kwan Blackwell Publishing Ltd 2011 Journal of Clinical Periodontology Vol.38 No.3

<P>Min C‐K, Wikesjö UME, Park J‐C, Chae G‐J, Pippig SD, Bastone P, Kim C‐S, Kim C‐K. Wound healing/regeneration using recombinant human growth/differentiation factor‐5 in an injectable poly‐lactide‐co‐glycolide‐acid composite carrier and a one‐wall intra‐bony defect model in dogs. J Clin Peridontol 2011; 38: 261–268. 38: 261–268. doi: 10.1111/j.1600‐051X.2010.01691.x.</P><P><B>Abstract</B></P><P><B>Objective: </B> The purpose of this study was to evaluate the effect of recombinant human growth/differentiation factor‐5 (rhGDF‐5) on periodontal wound healing/regeneration using an injectable poly‐lactide‐co‐glycolide‐acid (PLGA) composite carrier and an established defect model.</P><P><B>Methods: </B> Bilateral 4 × 5 mm (width × depth) one‐wall, critical‐size, intra‐bony periodontal defects were surgically created at the second and the fourth mandibular pre‐molar teeth in 15 Beagle dogs. The animals were randomized to receive (using a split‐mouth design; defect sites in the same jaw quadrant getting the same treatment) rhGDF‐5 high dose (188 <I>μ</I>g/defect) <I>versus</I> sham‐surgery control (five animals), rhGDF‐5 mid dose (37 <I>μ</I>g/defect) <I>versus</I> carrier control (five animals), and rhGDF‐5 low dose (1.8 <I>μ</I>g/defect) <I>versus</I> treatment reported elsewhere (five animals). The animals were euthanized for histometric analysis following an 8‐week healing interval.</P><P><B>Results: </B> Clinical healing was uneventful. The rhGDF‐5/PLGA construct was easy to assemble and apply. The rhGDF‐5 high dose supported significantly increased bone formation compared with the low‐dose, sham‐surgery, and carrier controls (<I>p</I><0.05) and induced significantly increased cementum formation compared with the controls (<I>p</I><0.05). Root resorption/ankylosis or other aberrant healing events were not observed.</P><P><B>Conclusion: </B> rhGDF‐5 appears to effectively support periodontal wound healing/regeneration in a dose‐dependent order; the PLGA composite appears to be an effective ease‐of‐use candidate for carrier technology.</P>

Serum Adipokine Concentrations in Dogs with Acute Pancreatitis

Paek, J.,Kang, J.&#x2010,H.,Kim, H.&#x2010,S.,Lee, I.,Seo, K.W.,Yang, M.&#x2010,P. John Wiley and Sons Inc. 2014 Journal of veterinary internal medicine Vol.28 No.6

<P><B>Background</B></P><P>Limited information is available about the role of adipokines in the development and progression of acute pancreatitis (AP) in dogs.</P><P><B>Objectives</B></P><P>To determine whether the circulating concentrations of adipokines differed between healthy dogs and dogs with AP, and whether the circulating concentrations differed between AP survivors and AP nonsurvivors.</P><P><B>Animals</B></P><P>Twenty‐eight healthy dogs and 25 client‐owned dogs with AP.</P><P><B>Methods</B></P><P>Prospective observational cohort study of 25 client‐owned dogs with newly diagnosed AP and 28 otherwise healthy dogs with similar body condition scores. The serum concentrations of leptin, adiponectin, resistin, visfatin, interleukin (IL)‐1β, IL‐6, IL‐10, IL‐18, and tumor necrosis factor (TNF)‐α were measured.</P><P><B>Results</B></P><P>The serum concentrations of leptin (<I>P </I>=<I> </I>.0021), resistin (<I>P </I>=<I> </I>.0010), visfatin (<I>P </I><<I> </I>.0001), IL‐1β (<I>P </I><<I> </I>.0001), IL‐6 (<I>P </I>=<I> </I>.0002), IL‐10 (<I>P </I><<I> </I>.0001), and IL‐18 (<I>P </I><<I> </I>.0001) were significantly higher in dogs with AP than healthy dogs, whereas the adiponectin concentration (<I>P </I>=<I> </I>.0011) was significantly lower. There were significant differences in the serum concentrations of leptin (<I>P </I>=<I> </I>.028) and adiponectin (<I>P </I>=<I> </I>.046) in survivors and nonsurvivors. After the disappearance of clinical signs, the concentrations of resistin (<I>P </I>=<I> </I>.037) and IL‐1β (<I>P </I>=<I> </I>.027) decreased significantly, whereas the serum concentrations of leptin (<I>P </I>><I> </I>.999), adiponectin (<I>P </I>=<I> </I>.11), visfatin (<I>P </I>=<I> </I>.83), IL‐6 (<I>P </I>=<I> </I>.82), IL‐10 (<I>P </I>=<I> </I>.82), IL‐18 (<I>P </I>=<I> </I>.56), and TNF‐α (<I>P </I>=<I> </I>.94) did not differ significantly.</P><P><B>Conclusion and Clinical Importance</B></P><P>This study showed that dysregulation of adipokines might be involved in the pathogenesis of AP. In addition, leptin and adiponectin are likely to be associated with mortality rate in AP.</P>