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If life satisfaction has functional significance for goal achievement, it should be calibrated to cues of potential success on active and fundamentally important goals. Within the context of mating motivation, we tested this hypothesis with self-perceived mate value—an assessment of one’s potential mating success. As hypothesized, because most individuals (eventually) seek long-term relationships, self-perceived long-term mate value predicted life satisfaction for men and women regardless of relationship status. In contrast, and also as hypothesized, self-perceived short-term mate value predicted life satisfaction only for individuals with short-term mating goals—single uncommitted men (Studies 1, 2A, and 2B), individuals dispositionally motivated toward short-term relationships (Studies 2A and 2B), and single uncommitted women for whom short-term mating motivation was experimentally engaged, enabling causal inference (Study 3). Results support a functional conceptualization of life satisfaction, showing that currently active mating goals can shape the extent to which goal-specific self-perceived mate value predicts life satisfaction.

Recurrent implantation failure (RIF) refers to two or more unsuccessful in vitro fertilization embryo transfers in the same individual. Embryonic characteristics, immunological factors, and coagulation factors are known to be the causes of RIF. Genetic factors have also been reported to be involved in the occurrence of RIF, and some single nucleotide polymorphisms (SNPs) may contribute to RIF. We examined SNPs in FSHR, INHA, ESR1, and BMP15, which have been associated with primary ovarian failure. A cohort of 133 RIF patients and 317 healthy controls consisting of all Korean women was included. Genotyping was performed by Taq-Man genotyping assays to determine the frequency of the following polymorphisms: FSHR rs6165, INHA rs11893842 and rs35118453, ESR1 rs9340799 and rs2234693, and BMP15 rs17003221 and rs3810682. The differences in these SNPs were compared between the patient and control groups. Our results demonstrate a decreased prevalence of RIF in subjects with the FSHR rs6165 A>G polymorphism [AA vs. AG adjusted odds ratio (AOR) = 0.432; confidence interval (CI) = 0.206–0.908; p = 0.027, AA+AG vs. GG AOR = 0.434; CI = 0.213–0.885; p = 0.022]. Based on a genotype combination analysis, the GG/AA (FSHR rs6165/ESR1 rs9340799: OR = 0.250; CI = 0.072–0.874; p = 0.030) and GG-CC (FSHR rs6165/BMP15 rs3810682: OR = 0.466; CI = 0.220–0.987; p = 0.046) alleles were also associated with a decreased RIF risk. Additionally, the FSHR rs6165GG and BMP15 rs17003221TT+TC genotype combination was associated with a decreased RIF risk (OR = 0.430; CI = 0.210–0.877; p = 0.020) and increased FSH levels, as assessed by an analysis of variance. The FSHR rs6165 polymorphism and genotype combinations are significantly associated with RIF development in Korean women.

Background Sarcopenia, defined as loss of muscle mass and strength with age, becomes a public health concern as the elderly population increases. This study aimed to determine whether the mixture of soluble whey protein hydrolysate (WPH) and Panax ginseng berry extract (GBE) has a synergetic effect on sarcopenia and, if so, to identify the relevant mechanisms and optimal mixing ratio. Methods In the first experiment, C57BL/6 mice were hindlimb immobilized for one-week and then administered WPH 800 mg/kg, GBE 100 mg/kg, WPH 800 mg/kg+ GBE 100 mg/kg mixture, and Fructus Schisandrae extract (SFE) 200 mg/kg for two weeks. In the second experiment, experimental design was same, but mice were administered three different doses of WPH and GBE mixture (WPH 800 mg/kg+ GBE 100 mg/kg, WPH 800 mg/kg+ GBE 90 mg/kg, WPH 1000 mg/kg+ GBE 75 mg/kg). Results In the first experiment, we confirmed the synergetic effect of WPH and GBE on muscle mass and identified that GBE was more effective on the protein synthesis side, and WPH tended to be slightly more effective for protein degradation. In the second experiment, among three different ratios, the WPH 800 mg/kg+ GBE 100 mg/kg was most effective for muscle mass and strength. The mixtures activated muscle protein synthesis via PI3K/Akt/mTORc1 pathway and inhibited muscle protein degradation via suppressing ubiquitin-proteasome system (UPS) and autophagy-lysosome system (ALS), and these effects were more GBE dose-dependent than WPH. Conclusion The WPH and GBE mixture having a synergetic effect is a potential agent to prevent sarcopenia.

Background Although metastasis is the foremost cause of cancer-related death, a specialized mechanism that reprograms anchorage dependency of solid tumor cells into circulating tumor cells (CTCs) during metastatic dissemination remains a critical area of challenge. Methods We analyzed blood cell-specific transcripts and selected key Adherent-to-Suspension Transition (AST) factors that are competent to reprogram anchorage dependency of adherent cells into suspension cells in an inducible and reversible manner. The mechanisms of AST were evaluated by a series of in vitro and in vivo assays. Paired samples of primary tumors, CTCs, and metastatic tumors were collected from breast cancer and melanoma mouse xenograft models and patients with de novo metastasis. Analyses of single-cell RNA sequencing (scRNA-seq) and tissue staining were performed to validate the role of AST factors in CTCs. Loss-of-function experiments were performed by shRNA knockdown, gene editing, and pharmacological inhibition to block metastasis and prolong survival. Results We discovered a biological phenomenon referred to as AST that reprograms adherent cells into suspension cells via defined hematopoietic transcriptional regulators, which are hijacked by solid tumor cells to disseminate into CTCs. Induction of AST in adherent cells 1) suppress global integrin/ECM gene expression via Hippo-YAP/TEAD inhibition to evoke spontaneous cell–matrix dissociation and 2) upregulate globin genes that prevent oxidative stress to acquire anoikis resistance, in the absence of lineage differentiation. During dissemination, we uncover the critical roles of AST factors in CTCs derived from patients with de novo metastasis and mouse models. Pharmacological blockade of AST factors via thalidomide derivatives in breast cancer and melanoma cells abrogated CTC formation and suppressed lung metastases without affecting the primary tumor growth. Conclusion We demonstrate that suspension cells can directly arise from adherent cells by the addition of defined hematopoietic factors that confer metastatic traits. Furthermore, our findings expand the prevailing cancer treatment paradigm toward direct intervention within the metastatic spread of cancer.

Acetylated microtubules play key roles in the regulation of mitochondria dynamics. It has however remained unknown if the machinery controlling mitochondria dynamics functionally interacts with the alpha-tubulin acetylation cycle. Mitofusin-2 (MFN2), a large GTPase residing in the mitochondrial outer membrane and mutated in Charcot-Marie-Tooth type 2 disease (CMT2A), is a regulator of mitochondrial fusion, transport and tethering with the endoplasmic reticulum. The role of MFN2 in regulating mitochondrial transport has however remained elusive. Here we show that mitochondrial contacts with microtubules are sites of alpha-tubulin acetylation, which occurs through the MFN2-mediated recruitment of alpha-tubulin acetyltransferase 1 (ATAT1). We discover that this activity is critical for MFN2-dependent regulation of mitochondria transport, and that axonal degeneration caused by CMT2A MFN2 associated mutations, R94W and T105M, may depend on the inability to release ATAT1 at sites of mitochondrial contacts with microtubules. Our findings reveal a function for mitochondria in regulating acetylated alpha-tubulin and suggest that disruption of the tubulin acetylation cycle play a pathogenic role in the onset of MFN2-dependent CMT2A.

Axon and dendrite placement and connectivity is guided by a wide range of secreted and surface molecules in the developing nervous system. Nevertheless, the extraordinary complexity of connections in the brain requires that this repertoire be further diversified to precisely and uniquely regulate cell-cell interactions. One important mechanism for molecular diversification is alternative splicing.Drosophila Down syndrome cell adhesion molecule (Dscam2) undergoes cell type-specific alternative splicing to produce two isoform-specific homophilic binding proteins. Regulated alternative splicing ofDscam2is important for dendrite and axon patterning, but how this translates to circuit wiring and animal behavior is not well understood. Here, we examined the role of cell-type specific expression ofDscam2isoforms in regulating synaptic partner selection in the larval somatosensory system. We found that synaptic partners in the nociceptive circuit express different Dscam2 isoforms. Forcing synaptic partners to express a common isoform resulted in nociceptive axon patterning defects and attenuated nocifensive behaviors, indicating that a role for Dscam2 alternative splicing is to ensure that synaptic partners do not express matching isoforms. These results point to a model in which regulated alternative splicing ofDscam2across populations of neurons restricts connectivity to specific partners and prevents inappropriate synaptic connections.

Disruptions in membrane trafficking are associated with neurodevelopmental disorders, but underlying pathological mechanisms remain largely unknown. In this issue, O’Brien et al. (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202112108) show how GARP regulates sterol transfer critical for remodeling of dendrites in flies.

Studies have been actively conducted to identify actionable mutations and incorporate them into clinical practice in pancreatic ductal adenocarcinoma (PDAC), which is known to have a poor prognosis with traditional cytotoxic chemotherapy. A BRAF point mutation in V600E is commonly reported in KRAS wild-type PDAC, and targeting BRAF_V600E is already being applied to various carcinomas, including PDAC. Accumulated evidence also shows that not only BRAF_V600E but also short in-frame deletions of BRAF have an oncogenic function. Here, we report that a patient with BRAF N486_P490 deletion initiated on dabrafenib or trametinib, a BRAF inhibitor, and a MEK inhibitor, respectively, after cytotoxic chemotherapy failure. The patient then presented with a partial response.

What kind of life do people want? In psychology, a good life has typically been conceptualized in terms of either hedonic or eudaimonic well-being. We propose that psychological richness is another neglected aspect of what people consider a good life. In study 1 (9-nation cross-cultural study), we asked participants whether they ideally wanted a happy, a meaningful, or a psychologically rich life. Roughly 7 to 17% of participants chose the psychologically rich life. In study 2, we asked 1611 Americans and 680 Koreans what they regret most in their lives; then, if they could undo or reverse the regretful event, whether their lives would have been happier, more meaningful, or psychologically richer as a result. Roughly 28% of Americans and 35% of Koreans reported their lives would have been psychologically richer. Together, this work provides a foundation for the study of psychological richness as another dimension of a good life. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s42761-020-00011-z) contains supplementary material, which is available to authorized users.

Purpose: Although the taller-than-wide (TTW) sign has been regarded as one of the most specific ultrasound (US) features of thyroid malignancy, uncertainty still exists regarding the US probe’s orientation when evaluating it. This study investigated which US plane would be optimal to identify the TTW sign based on malignancy risk stratification using a registry-based imaging dataset.Methods: A previous study by 17 academic radiologists retrospectively analyzed the US images of 5,601 thyroid nodules (≥1 cm, 1,089 malignant and 4,512 benign) collected in the webbased registry of Thyroid Imaging Network of Korea through the collaboration of 26 centers. The present study assessed the diagnostic performance of the TTW sign itself and fine needle aspiration (FNA) indications via a comparison of four international guidelines, depending on the orientation of the US probe (criterion 1, transverse plane; criterion 2, either transverse or longitudinal plane).Results: Overall, the TTW sign was more frequent in malignant than in benign thyroid nodules (25.3% vs. 4.6%). However, the statistical differences between criteria 1 and 2 were negligible for sensitivity, specificity, and area under the curve (AUC) based on the size effect (all P0.05, respectively).Conclusion: A longitudinal US probe orientation provided little additional diagnostic value over the transverse orientation in detecting the TTW sign of thyroid nodules.

Recurrent pregnancy loss (RPL) is typically defined as two or more consecutive pregnancy losses prior to 20 weeks of gestation. Although the causes of idiopathic RPL are not completely understood, vascular development and glucose concentration were reported to correlate with the pregnancy loss. The TGF-β signaling pathway which plays a significant role in pregnancy is activated by the interaction between high glucose and SMAD signaling and affects the vascular cells.

Background In foot and ankle infections, cases with apparent soft-tissue necrosis or purulent fluid collections definitely require surgical treatments. However, clinicians often have difficulty in determining whether to perform surgery in ambiguous cases without these findings. This study aimed to investigate the impact of the delta neutrophil index as a predictor of surgical treatment in patients with foot and ankle infections. Methods In total, 66 patients diagnosed with foot and ankle infections who underwent the delta neutrophil index test were retrospectively investigated. Medical records, including data on diabetes mellitus status, delta neutrophil index values, white blood cell count, polymorphonuclear leukocyte count, erythrocyte sedimentation rate, and C-reactive protein level, were retrospectively investigated. Logistic regression models were analyzed for the correlation between biomarkers, such as the delta neutrophil index and surgical treatment. The area under the curve was investigated to evaluate the cut-off value of the logistic model in predicting surgery. Results The relationship between the delta neutrophil index and surgical treatment was analyzed. The delta neutrophil index, adjusted for diabetes mellitus, was the best predictor of future surgical intervention. Based on the Youden index, the cutoff point (the equation’s adjusted by diabetes mellitus) for the prediction of surgical treatment was defined as a probability of 0.3, with sensitivity and specificity of 82.4% and 77.6%, respectively. Conclusions Based on the present study, the delta neutrophil index can help clinicians decide the appropriate surgical treatment for foot and ankle infections at the right time.

Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and complex condition arising from chemotherapy cancer treatments. Currently, there are no treatment or prevention options in the clinic. CIPN accompanies pain-related sensory functions starting from the hands and feet. Studies focusing on neurons

We conducted this single-center, retrospective study to identify predictors of upgrading to malignancy and to discuss the necessity of additional excision biopsy in patients who were diagnosed with atypical ductal hyperplasia (ADH) at ultrasound (US)-guided vacuum-assisted breast biopsy (VABB) based on our 18-year, single-center experience.The current study was conducted in a total of 12,160 patients who were evaluated at our medical institution during an 18-year period between January of 2003 and December of 2020. We included the patients who were diagnosed with ADH at US-guided VABB using the MammotomeOf 114 eligible patients, 36 underwent additional excision biopsy and the remaining 78 did not. Of these 36 patients, 15 were found to have an upgrading to malignancy at a rate of upgrading of 41.7%. These include 7 cases (46.6%) of low-grade ductal carcinoma in situ (DCIS), 3 cases (20.0%) of intermediate grade DCIS, 1 case (6.7%) of microinvasive DCIS, 3 cases (20.0%) of multifocal lobular carcinoma in situ, and 1 case (6.7%) of mucinous carcinoma. Finally, only suspicious microcalcification on mammography was a significant predictor of upgrading to malignancy (p=0.023).An additional excision biopsy is recommended to reduce the rate of upgrading to malignancy in patients who were diagnosed with ADH through a US-guided VABB.

47 Background: The standard treatment for synchronous stage IV colorectal cancer (CRC) is systemic chemotherapy. There have been attempts to conduct elective primary tumor resection (PTR) as an upfront treatment to prevent complications in primary tumor sites, or improve prognosis. However, there are controversies about the role of PTR in stage IV CRC. We investigated the prognostic role of PTR and tried to find subgroups who might get benefit from upfront PTR in this population. Methods: Between 2010 and 2020, 330 patients diagnosed with synchronous stage IV CRC at St. Vincent Hospital in Korea were retrospectively reviewed. We excluded patients underwent PTR and metastasectomy at the same time, PTR for emergencies (perforation, acute bleeding with hemodynamic instability, fistula, and/or obstruction), or received chemoradiotherapy as an initial treatment. Overall survival (OS) was measured from the date of diagnosis until death resulting from any cause or the last censored date during follow-up. OS were calculated using the Kaplan-Meier method, and differences in survival between groups were compared by the log-rank test. Variables with p value

Paclitaxel is a common chemotherapeutic agent widely used to treat solid cancer. However, it frequently causes peripheral sensory neuropathy, resulting in sensory abnormalities and pain in patients receiving treatment for cancer. As one of the most widely used chemotherapeutics, many preclinical studies on paclitaxel-induced peripheral neuropathy (PIPN) have been performed. Yet, there remain no effective options for treatment or prevention. Due to paclitaxel's ability to bind to and stabilize microtubules, a change in microtubule dynamics and subsequent disruptions in axonal transport has been predicted as a major underlying cause of paclitaxel-induced toxicity. However, the systemic understanding of PIPN mechanisms is largely incomplete, and various phenotypes have not been directly attributed to microtubule-related effects. This review aims to provide an overview of the literature involving paclitaxel-induced alteration in microtubule dynamics, axonal transport, and endocytic changes. It also aims to provide insights into how the microtubule-mediated hypothesis may relate to various phenotypes reported in PIPN studies.

Background The genetic interactions in the circadian rhythm biological system are promising as a source of pathophysiology in mood disorder. We examined the role of the gene–gene interactions of clock genes in mood disorder. Methods We included 413 patients with mood disorder and 1294 controls. The clock genes investigated were BHLHB2, CLOCK, CSNK1E, NR1D1, PER2, PER3, and TIMELESS. Allele, genotype, and haplotype associations were tested. Gene–-gene interactions were analyzed using the non-parametric model-free multifactor-dimensionality reduction (MDR) method. Results TIMELESS rs4630333 and CSNK1E rs135745 were significantly associated with both major depressive disorder and bipolar disorder. The CLOCK haplotype was also strongly associated. The genetic roles of these SNPs were consistent from the allele and genotypic associations to the MDR interaction results. In MDR analysis, the combination of TIMELESS rs4630333 and CSNK1E rs135745 exhibited the most significant association with mood disorders in the two-locus model. BHLHB2 rs2137947 for major depressive disorder and CLOCK rs12649507 for bipolar disorder were the most significant third loci in the three-locus combination model. The four-locus SNP combination model showed the best balanced accuracy (BA), but its cross-validation consistency (CVC) was unsatisfactory. Limitations We included only 17 SNPs for seven circadian genes due to our limited resources; all subjects were ethnically Korean. Conclusions Our results suggest significant single-gene associations and gene–gene interactions of circadian genes with mood disorder. Gene–gene interactions play a crucial role in mood disorder, even when individual clock genes do not have significant roles.

This paper presented an efficient multiband FSK signals with direct sequence spread spectrum for maintaining covertness and performance. In aspect to covertness, direct sequence spread spectrum method, which multiplying by PN codes whose rate is much higher than that of data sequence, is employed. In aspect to performance, we applied multiband, turbo equalization, and weighting algorithm. Underwater acoustic communication experiments were conducted in the lake. In the lake experimental results, we confirmed that the performance was improved as the number of bands and chips are increased. Furthermore, the performance of multiband was improved when the proposed weighting algorithm was applied.

The multi-band UWAS communication techniques are effective in terms of performance and throughput efficiency. However, the multi-band configuration in a particular band affects the output from the entire bands. This problem can be solved through a receiving end that analyzes error rates of each band. In this paper, we proposed an estimation BER algorithm which get the reliability of received data to set the weighting value to each band. Therefore, we analyzed the efficiency of multi-band transmission scheme with estimation BER and 3 [dB] performance gain is obtained.

Ginsenoside Re (G-Re) is a panaxatriol saponin and one of the pharmacologically active natural constituents of ginseng (Panax ginseng C.A. Meyer). G-Re has antioxidant, anti-inflammatory and antidiabetic effects. The present study aimed to investigate the effects of G-Re on neuroinflammatory responses in lipopolysaccharide (LPS)-stimulated microglia and its protective effects on hippocampal neurons. Cytokine levels were measured using ELISA and reactive oxygen species (ROS) levels were assessed using flow cytometry and fluorescence microscopy. Protein levels of inflammatory molecules and kinase activity were assessed by western blotting. Cell viability was assessed by MTT assay; apoptosis was estimated by Annexin V apoptosis assay. The results revealed that G-Re significantly inhibited the production of IL-6, TNF-α, nitric oxide (NO) and ROS in BV2 microglial cells, and that of NO in mouse primary microglia, without affecting cell viability. G-Re also inhibited the nuclear translocation of NF-κB, and phosphorylation and degradation of IκB-α. In addition, G-Re dose-dependently suppressed LPS-mediated phosphorylation of Ca2+/calmodulin-dependent protein kinase (CAMK)2, CAMK4, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinases (JNK). Moreover, the conditioned medium from LPS-stimulated microglial cells induced HT22 hippocampal neuronal cell death, whereas that from microglial cells incubated with both LPS and G-Re ameliorated HT22 cell death in a dose-dependent manner. These results suggested that G-Re suppressed the production of pro-inflammatory mediators by blocking CAMK/ERK/JNK/NF-κB signaling in microglial cells and protected hippocampal cells by reducing these inflammatory and neurotoxic factors released from microglial cells. The present findings indicated that G-Re may be a potential treatment option for neuroinflammatory disorders and could have therapeutic potential for various neurodegenerative diseases.

Sarcopenia, defined as loss of muscle mass and strength with age, becomes a public health concern as the elderly population increases. This study aimed to determine whether the mixture of soluble whey protein hydrolysate (WPH) andIn the first experiment, C57BL/6 mice were hindlimb immobilized for one-week and then administered WPH 800 mg/kg, GBE 100 mg/kg, WPH 800 mg/kg+ GBE 100 mg/kg mixture, andIn the first experiment, we confirmed the synergetic effect of WPH and GBE on muscle mass and identified that GBE was more effective on the protein synthesis side, and WPH tended to be slightly more effective for protein degradation. In the second experiment, among three different ratios, the WPH 800 mg/kg+ GBE 100 mg/kg was most effective for muscle mass and strength. The mixtures activated muscle protein synthesis via PI3K/Akt/mTORc1 pathway and inhibited muscle protein degradation via suppressing ubiquitin-proteasome system (UPS) and autophagy-lysosome system (ALS), and these effects were more GBE dose-dependent than WPH.The WPH and GBE mixture having a synergetic effect is a potential agent to prevent sarcopenia.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect from cancer treatment with no known method for prevention or cure in clinics. CIPN often affects unmyelinated nociceptive sensory terminals. Despite the high prevalence, molecular and cellular mechanisms that lead to CIPN are still poorly understood. Here, we used a genetically tractable Drosophila model and primary sensory neurons isolated from adult mouse to examine the mechanisms underlying CIPN and identify protective pathways. We found that chronic treatment of Drosophila larvae with paclitaxel caused degeneration and altered the branching pattern of nociceptive neurons, and reduced thermal nociceptive responses. We further found that nociceptive neuron-specific overexpression of integrins, which are known to support neuronal maintenance in several systems, conferred protection from paclitaxel-induced cellular and behavioral phenotypes. Live imaging and superresolution approaches provide evidence that paclitaxel treatment causes cellular changes that are consistent with alterations in endosome-mediated trafficking of integrins. Paclitaxel-induced changes in recycling endosomes precede morphological degeneration of nociceptive neuron arbors, which could be prevented by integrin overexpression. We used primary dorsal root ganglia (DRG) neuron cultures to test conservation of integrin-mediated protection. We show that transduction of a human integrin β-subunit 1 also prevented degeneration following paclitaxel treatment. Furthermore, endogenous levels of surface integrins were decreased in paclitaxel-treated mouse DRG neurons, suggesting that paclitaxel disrupts recycling in vertebrate sensory neurons. Altogether, our study supports conserved mechanisms of paclitaxel-induced perturbation of integrin trafficking and a therapeutic potential of restoring neuronal interactions with the extracellular environment to antagonize paclitaxel-induced toxicity in sensory neurons.

Mutations in Fms-like tyrosine kinase 3 (FLT3) have been implicated in the pathogenesis of acute myeloid leukemia (AML) by affecting the proliferation and differentiation of hematopoietic stem and progenitor cells. Although several FLT3 inhibitors have been developed, the occurrence of secondary TKD mutations of FLT3 such FLT3/D835Y and FLT3/F691L lead to drug resistance and has become a key area of unmet medical needs. To overcome the obstacle of secondary TKD mutations, a new series of indirubin-3'-aminooxy-acetamide derivatives was discovered as potent and selective FLT3 and FLT3/D835Y inhibitors that were predicted to bind at the DFG-in active conformation of FLT3 in molecular docking studies. Through structure-activity relationship studies, the most optimized compound 13a was developed as a potent inhibitor at FLT3 and FLT3/D835Y with IC

The pathogenesis of chemotherapy-induced peripheral neuropathy (CIPN) is poorly understood. Here, we report that the CIPN-causing drug bortezomib (Bort) promotes delta 2 tubulin (D2) accumulation while affecting microtubule stability and dynamics in sensory neurons in vitro and in vivo and that the accumulation of D2 is predominant in unmyelinated fibers and a hallmark of bortezomib-induced peripheral neuropathy (BIPN) in humans. Furthermore, while D2 overexpression was sufficient to cause axonopathy and inhibit mitochondria motility, reduction of D2 levels alleviated both axonal degeneration and the loss of mitochondria motility induced by Bort. Together, our data demonstrate that Bort, a compound structurally unrelated to tubulin poisons, affects the tubulin cytoskeleton in sensory neurons in vitro, in vivo, and in human tissue, indicating that the pathogenic mechanisms of seemingly unrelated CIPN drugs may converge on tubulin damage. The results reveal a previously unrecognized pathogenic role for D2 in BIPN that may occur through altered regulation of mitochondria motility.

Recurrent pregnancy loss (RPL) is typically defined as two or more consecutive pregnancy losses prior to 20 weeks of gestation. Although the causes of idiopathic RPL are not completely understood, vascular development and glucose concentration were reported to correlate with the pregnancy loss. The TGF-β signaling pathway which plays a significant role in pregnancy is activated by the interaction between high glucose and SMAD signaling and affects the vascular cells. SMAD5 and RUNX-1 are involved in the TGF-β signaling pathway and contribute to advanced glycation end products (AGEs) production and vascular development. FN3KRP, a newly described gene, is also associated with vascular diseases and suggested to relate to AGEs. Therefore, in the present study, we investigated associations between RPL risk and genetic polymorphisms of SMAD5, FN3KRP, and RUNX-1 in 388 women with RPL and 280 healthy control women of Korean ethnicity. Participants were genotyped using real-time polymerase chain reaction and restriction fragment length polymorphism assay to determine the frequency of SMAD5 rs10515478 C>G, FN3KRP rs1046875 G>A, and RUNX-1 rs15285 G>A polymorphisms. We found that women with RPL had lower likelihoods of the FN3KRP rs1046875 AA genotype (adjusted odds ratio (AOR), 0.553; p = 0.010) and recessive model (AOR, 0.631; p = 0.017). Furthermore, combination analysis showed that SMAD5 rs10515478 C>G and FN3KRP rs1046875 G>A mutant alleles were together associated with reduced RPL risk. These findings suggest that the FN3KRP rs1046875 G>A polymorphism has a significant role on the prevalence of RPL in Korean women. Considering that it is the first study indicating a significant association between FN3KRP and pregnancy disease, RPL, our results suggest the need for further investigation of the role of FN3KRP in pregnancy loss.

Sarcopenia and obesity are serious health problems that are highly related to several metabolic diseases. Sarcopenic obesity, a combined state of sarcopenia and obesity, results in higher risks of metabolic diseases and even mortality than sarcopenia or obesity alone. Therefore, the development of therapeutic agents for sarcopenic obesity is crucial. C57BL/6 mice were fed with a high-fat diet (HFD) for 9 weeks. Then, mice were administered with Panax ginseng berry extract (GBE) for an additional 4 weeks, with continuous HFD intake. GBE significantly decreased the food efficiency ratio, serum lipid and insulin levels, adipose tissue weights, and adipocyte size. It significantly increased the grip strength, muscle masses, and myofiber cross-sectional area. It deactivated the protein kinase C (PKC) theta and zeta, resulting in activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, which is known to regulate muscle synthesis and degradation. Furthermore, it inhibited the production of inflammatory cytokines in the muscle tissue. GBE attenuated both obesity and sarcopenia. Thus, GBE is a potential agent to prevent or treat sarcopenic obesity.

This study was conducted to assess the changes in the annual incidence of adult asthma in Korea where the prevalence of asthma had increased steadily in recent decades. A population-based cohort study was conducted using the National Health Insurance Service–National Sample Cohort (NHIS-NSC), which consisted of 746,816 adults aged >20 years between 2004 and 2012. Asthma was defined by two or more physician claims on the basis of a primary diagnostic code for asthma and administration of asthma medications within 1 year. The incidence rates and annual percent change were calculated, and the influence of age and sex on the incidence rates was studied. The annual asthma incidence increased from 3.63 in 2004 to 6.07 per 1,000 person-years in 2008. Since 2008, the asthma incidence did not change significantly. The asthma incidence was higher in women than in men throughout the study periods (p

BACKGROUND/AIM Recently, the development of ultrasonography (US)-guided vacuum-assisted breast biopsy (VABB) has enabled the excision of benign breast tumors with normal surrounding breast tissues; thus, complete excision is possible without residual tumor tissue. We sought to identify the clinicopathological characteristics and recurrence rates of benign phyllodes tumors diagnosed by US-guided VABB. PATIENTS AND METHODS Data from 11,221 US-guided VABBs performed at the Gangnam Cha Medical Center over 12 years were analyzed. Eighty-three lesions were diagnosed as benign phyllodes tumors; 67 with >24 months of follow-up data were investigated. All lesions were excised using an 8-gauge probe without residual tissue; patients underwent follow-up US every 3-6 months. RESULTS Five patients (7.46%) experienced local recurrence during a mean follow-up period of 27.8 months; no distant metastases occurred. The mean tumor size was 3.0 cm in the recurrence group and 1.87 cm in the non-recurrence group (p=0.05). CONCLUSION Benign phyllodes tumors excised and diagnosed using VABB showed a low recurrence rate during the follow-up period; thus, these tumors, particularly those

Physical attractiveness (PAT), despite its allure in everyday life, has been an inconsistent predictor of happiness in past studies. In this research, we find that a lay belief about the locus of a person's “essence” moderates the PAT and happiness link. Specifically, we measured how strongly one believes in the diagnostic value of the visible (e.g., status, appearance) over the invisible (e.g., mood, thoughts) aspects of a person in understanding who s/he is. As expected, the more one believed in the value of the visible features, the more central PAT was in the person's overall life, and appearance was compared more often with others (Study 1). More importantly, PAT and well-being correlated significantly only among those who strongly endorsed the visible selfhood belief (Study 2). Compared to past studies on PAT that relied heavily on self-reports, a highly objective measure of attractiveness (waist-to-hip ratio) was employed in this research. Our research uncovers a novel individual difference factor that helps to clarify why PAT predicts the happiness of some, but not of others. Whether one thinks a person's essence can be judged by one's “cover” seems to matter in the PAT and happiness link.

The present study examined cultural differences in the act of sharing positive events with others, called capitalization attempts. The first three studies tested whether capitalization attempts differ between two cultures using multiple methods: self-reports (Study 1), children’s storybooks (Study 2), and Facebook (Study 3). We found that Koreans are less likely to share their positive events with others than European Americans. Study 4 further examined the antecedents and consequences of capitalization attempts. We replicated the earlier findings that Koreans are hesitant to share their positive events and demonstrated that this is because Koreans are more concerned about the potential negative consequences for social relationships. Moreover, we found that the cultural differences in capitalization attempts partly account for mean-level differences in well-being between cultures. Implications for capitalization, culture, and well-being are discussed.

L’objectif de cet article est de comprendre les caracteristiques du don d’organes post mortem en termes d’unilateralite, de dette et de rapport a autrui. En partant de l’analyse du don d’organes dans la perspective de l’echange asymetrique de la vie et de la mort, cet article commence par examiner la specificite des sentiments de dette et de culpabilite que certains receveurs ont vecus apres la transplantation d’organes. Dans un deuxieme temps, il propose une analyse critique des discours mecaniste et utilitariste qui visent a reduire les organes humains a une substance sans âme. Ensuite, nous montrerons comment un receveur tente de se lier avec son donneur mort par le biais d’une parente fictive. En examinant ce temoignage, nous pourrons voir dans quelle mesure le receveur arrive enfin a accepter l’organe du donneur et a etablir un rapport imaginaire avec lui.