Spatial Disparities in SME Productivity: Evidence from the Service Sector in England

This paper identifies the key determinants of spatial variability of productivity, focusing on small and medium-sized enterprises (SMEs) in the service sector across England. Due to the hierarchically structured data, multilevel analysis is applied to distinguish the effects of a firm's internal variables and (sub)regional factors on productivity. Using cross-sectional data for 10,400 SMEs from the UK government's Small Business Survey, 2015, the results show that firm-specific determinants significantly influence productivity. The findings also indicate that location, local enterprise partnerships (LEPs) and where firms operate play a pivotal role in determining SME productivity. In particular, at the LEP level, increasing labour supply, promoting local funding and improving broadband speed potentially enhance firm productivity

The pattern of bowel dysfunction in patients with rectal cancer following the multimodal treatment: anorectal manometric measurements at before and after chemoradiation therapy, and postoperative 1 year

Purpose Bowel dysfunction commonly occurs in patients with locally advanced rectal cancer treated with a multimodal approach of chemoradiation therapy (CRT) combined with sphincter-preserving rectal resection. This study investigated the decline in anorectal function using sequential anorectal manometric measurements obtained before and after the multimodal treatment as well as at a 1-year follow-up. Methods This was a retrospective cohort study conducted in a single center. The study population consisted of patients with locally advanced mid- to low rectal cancer who received the preoperative CRT followed by sphincter-preserving surgery from 2012 to 2016. The anorectal manometric value measured after each treatment modality was compared to demonstrate the degree of decline in anorectal function. A generalized linear model of repeated measures was performed using the manometric values measured pre- and post-CRT, and at 12 months postoperatively. Results Overall, 100 patients with 3 consecutive manometric data were included in the final analysis. In the overall cohort study, the mean resting and maximal squeezing pressures showed insignificant decrement post-neoadjuvant CRT. At a 1-year postoperative follow-up, the maximal squeezing pressure significantly decreased. The maximal rectal sensory threshold demonstrated significant reduction consecutively after each following treatment (P<0.001). Conclusion The short-term effect of neoadjuvant CRT on the anal sphincters was relatively trivial. The following sphincter-saving surgery resulted in a profound disruption of the anorectal function. Patients with rectal cancer should be consulted on the consequence of multimodal treatment

Curative Effects of Thiacremonone against Acetaminophen-Induced Acute Hepatic Failure via Inhibition of Proinflammatory Cytokines Production and Infiltration of Cytotoxic Immune Cells and Kupffer Cells

High doses of acetaminophen (APAP; N-acetyl-p-aminophenol) cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500 mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50 mg/kg). Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1α, MIP-1β, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity

Heat shock protein 70 increases cell proliferation, neuroblast differentiation, and the phosphorylation of CREB in the hippocampus

In the present study, we investigated the effects of heat shock protein 70 (HSP70) on novel object recognition, cell proliferation, and neuroblast differentiation in the hippocampus. To facilitate penetration into the blood–brain barrier and neuronal plasma membrane, we created a Tat-HSP70 fusion protein. Eight-week-old mice received intraperitoneal injections of vehicle (10% glycerol), control-HSP70, or Tat-HSP70 protein once a day for 21 days. To elucidate the delivery efficiency of HSP70 into the hippocampus, western blot analysis for polyhistidine was conducted. Polyhistidine protein levels were significantly increased in control-HSP70- and Tat-HSP70-treated groups compared to the control or vehicle-treated group. However, polyhistidine protein levels were significantly higher in the Tat-HSP70-treated group compared to that in the control-HSP70-treated group. In addition, immunohistochemical study for HSP70 showed direct evidences for induction of HSP70 immunoreactivity in the control-HSP70- and Tat-HSP70-treated groups. Administration of Tat-HSP70 increased the novel object recognition memory compared to untreated mice or mice treated with the vehicle. In addition, the administration of Tat-HSP70 significantly increased the populations of proliferating cells and differentiated neuroblasts in the dentate gyrus compared to those in the control or vehicle-treated group based on the Ki67 and doublecortin (DCX) immunostaining. Furthermore, the phosphorylation of cAMP response element-binding protein (pCREB) was significantly enhanced in the dentate gyrus of the Tat-HSP70-treated group compared to that in the control or vehicle-treated group. Western blot study also demonstrated the increases of DCX and pCREB protein levels in the Tat-HSP70-treated group compared to that in the control or vehicle-treated group. In contrast, administration of control-HSP70 moderately increased the novel object recognition memory, cell proliferation, and neuroblast differentiation in the dentate gyrus compared to that in the control or vehicle-treated group. These results suggest that Tat-HSP70 promoted hippocampal functions by increasing the pCREB in the hippocampus.This work was supported by the Promising-Pioneering Researcher Program through Seoul National University (SNU) in 2015 and by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. NRF-2016R1A2B4009156 and NRF-2018R1A2B6001941). In addition, this study was partially supported by the Research Institute for Veterinary Science of Seoul National University

Adult Hippocampal Neurogenesis Can Be Enhanced by Cold Challenge Independently From Beigeing Effects

In this study, we investigated the effects of cold challenge on adult hippocampal neurogenesis (AHN) and hippocampal gene expression and whether these are mediated by beigeing of peripheral fat tissues. Cold challenge (6 ± 2°C) for 1 and 4 weeks was found to induce beigeing effects in inguinal white adipose tissue based on hematoxylin and eosin staining as well as uncoupled protein-1 immunohistochemical staining. In the hippocampus, cold challenge for 1 or 4 weeks increased dentate gyrus neurogenesis and expression of genes related to AHN, including notch signaling, G protein-coupled receptor signaling, and adrenergic beta receptor-1. However, this enhancement of neurogenesis and gene expression by cold challenge was not shown by administration of CL 316,243, which induces peripheral beigeing similar to cold challenge but does not cross the blood–brain barrier. These results suggest that cold challenge promotes AHN and central expression of AHN-related, signaling, and β1-adrenergic receptors genes, and that peripheral beigeing by itself is not sufficient to mediate these effects. Considering the increase in AHN and gene expression changes, cold challenge may offer a novel approach to hippocampal modulation

Induction of transforming growth factor-beta 1 by androgen is mediated by reactive oxygen species in hair follicle dermal papilla cells

The progression of androgenetic alopecia is closely related toandrogen-inducible transforming growth factor (TGF)-β1 secretionby hair follicle dermal papilla cells (DPCs) in bald scalp.Physiological levels of androgen exposure were reported toincrease reactive oxygen species (ROS) generation. In thisstudy, rat vibrissae dermal papilla cells (DP-6) transfected withandrogen receptor showed increased ROS production followingandrogen treatment. We confirmed that TGF-β1 secretion isincreased by androgen treatment in DP-6, whereas androgeninducibleTGF-β1 was significantly suppressed by the ROSscavenger,N-acetyl cysteine. Therefore, we suggest that inductionof TGF-β1 by androgen is mediated by ROS in hair follicleDPCs.This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant No. A103017) and partially by a research agreement with AmorePacific Corporation, Republic of Korea.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000045457/8SEQ:8PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000045457ADJUST_YN:NEMP_ID:A079130DEPT_CD:801CITE_RATE:1.634FILENAME:(460-464)bmb 12-228.pdfDEPT_NM:의학과EMAIL:[email protected]_YN:YCONFIRM:

Impact of a multidomain lifestyle intervention on white matter integrity: the SUPERBRAIN exploratory sub-study

In the South Korean study to prevent cognitive impairment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), we evaluated the impact of a 24-week facility-based multidomain intervention (FMI) and home-based MI (HMI) on white matter integrity. Among 152 participants, aged 60–79 years without dementia but with ≥1 modifiable dementia risk factor, 19 FMI, 20 HMI, and 16 controls underwent brain MRI at baseline and 24 weeks. Between the intervention and control groups, we compared changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) at regions-of-interest (ROI) including the cingulum cingulate gyrus (CgC), cingulum hippocampus (CgH), superior longitudinal fasciculus (SLF), as well as the uncinate fasciculus (UF). In addition, correlations between total and standard scores cognitive domains of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) or serum brain-derived neurotrophic factor (BDNF) and changes in brain image measures were evaluated at a statistical significance level of p &lt; 0.05 (uncorrected for multiple corrections). The FA, MD, AD, and RD at each ROI at the baseline were not different among groups after Bonferroni correction. In the statistical analysis using two-way repeated measures ANOVA, any significant difference in longitudinal changes in the FA, MD, AD, and RD was not revealed. The statistical analysis, among the significant regions in paired t-test of the intervention group, compared with the control group, the FMI, HMI, and intervention group yielded significantly more beneficial effects on the AD of the CgC. In addition, longitudinal AD changes of the left CgC correlated with the BDNF changes (r = 0.280, p = 0.048). In this study, enhanced cognitive reserve after the multidomain lifestyle intervention could be revealed by changes in brain imaging for white matter integrity