bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renal sodium glucose cotransporter 2 inhibitors as a novel therapeutic approach to treatment of type 2 diabetes: Clinical data and mechanism of action
Authors: Fujita Yoshihito , Inagaki Nobuya 
Published: April 2014

AbstractType 2 diabetes is characterized by impaired insulin secretion from pancreatic β‐cells and/or reduced response of target tissues to insulin. Good glycemic control delays the development and slows the progression of micro‐ and macrovascular complications. Although there are numerous glucose‐lowering agents in clinical use, only approximately half of type 2 diabetic patients achieve glycemic control, and undesirable side‐effects often hamper treatment in those treated with the medications. There is a need for novel treatment options that can help overcome these difficulties. Sodium glucose cotransporter 2 (SGLT2) inhibitors have recently been developed as a novel potential therapeutic option for the treatment of type 2 diabetes. These drugs lower the plasma glucose concentration through inhibition of glucose reuptake in the kidney, independent of insulin secretion and insulin action, with a consequent lower risk of hypoglycemia. The data of clinical trials with monotherapy as well as combination therapy show that SGLT2 inhibitors have a blood glucose‐lowering effect and also reduce bodyweight. A follow‐up study shows long‐term efficacy and the durability of these effects. SGLT2 inhibitors have the potential to reverse glucose toxicity, and to improve insulin resistance, blood pressure and lipid profile. The available data suggest a good tolerability profile. However, clinicians should carefully prescribe these drugs in light of already reported and/or unexpected side‐effects. Further studies in larger numbers and longer‐term clinical use data are required to place these agents in standard treatment of type 2 diabetes.
Change in Inflammatory Markers and Cognitive Status in the Oldest‐Old Women from the Study of Osteoporotic Fractures
Authors: Metti Andrea L. , Yaffe Kristine , Boudreau Robert M. , Ganguli Mary , Lopez Oscar L. , Stone Katie L. , Cauley Jane A. 
Published: April 2014

ObjectivesTo determine the association between interleukin‐6 (IL‐6), IL‐6 soluble receptor (sR), and soluble tumor necrosis factor receptor‐1 (sTNF‐R1) and cognitive status in the oldest‐old women.DesignTwenty‐year longitudinal cohort study.SettingFour clinical sites in the United States.ParticipantsWomen from the Study of Osteoporotic Fractures (N = 905; mean age 88.3 ± 2.8 at cognitive status adjudication).MeasurementsAt Year 20, cognitive status was adjudicated as normal, mild cognitive impairment (MCI), or dementia. Inflammatory markers were measured from blood serum at Years 10 and 16 in a random sample of women.ResultsOver 10 years, 199 (22.0%) women developed MCI and 145 (16.0%) dementia. There were no significant associations between IL‐6 or sTNF‐R1 and cognitive status. High IL‐6‐sR (≥37,401.36 pg/mL, highest tertile) at Year 16 was significantly associated with lower risk of dementia (odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.30–0.97) than in women with lower levels (<37,401.36 pg/mL, lower two tertiles). Women with high IL‐6‐sR at both time points (OR = 0.39, 95% CI = 0.17–0.89) or who transitioned to a high level (OR = 0.35, 95% CI = 0.14–0.88) had a lower risk of dementia.ConclusionIn this cohort of white, high‐functioning oldest‐old women, a consistently high or an increasing level of IL‐6‐sR was associated with lower risk of dementia. Compared with other studies of younger‐old adults, this suggests that the effect of inflammation on dementia may differ in younger‐old and the oldest‐old individuals. Understanding these differences will be crucial in interpreting results from ongoing clinical trials and in targeting therapeutic strategies to the oldest‐old individuals.
Identifying Common Characteristics of Frailty Across Seven Scales
Authors: Theou Olga , Brothers Thomas D. , Peña Fernando G. , Mitnitski Arnold , Rockwood Kenneth 
Published: April 2014

ObjectivesTo determine whether commonly used frailty scales exhibit shared characteristics when applied to a representative sample of middle‐aged and older Europeans.DesignSecondary analysis of the Survey of Health, Ageing, and Retirement in Europe (SHARE).SettingEleven European countries.ParticipantsCommunity‐dwelling adults (N = 27,527; mean age 65.3 ± 10.5, 55% female).MeasurementsFrailty was assessed using SHARE‐operationalized versions of seven frailty scales: Edmonton Frail Scale, FRAIL scale, Groningen Frailty Indicator, frailty phenotype, Tilburg Frailty Indicator, a 70‐item frailty index (FI), and a 44‐item frailty index based on Comprehensive Geriatric Assessment.ResultsAll frailty scales demonstrated right‐skewed density distributions. On all scales, frailty scores increased nonlinearly with age, between 1% (FRAIL) and 3.6% (FI) per year on a log scale. Frailty scores on all scales exhibited dose‐response relationships with 5‐year mortality. On all scales, women had higher frailty scores than men of the same age but demonstrated better survival than did men with the same frailty score. On all scales except the frailty phenotype, 99% of participants had scores below the scale's theoretical maximum.ConclusionOn each frailty scale, frailty score increased nonlinearly with age, mortality risk increased with frailty score, and women had higher scores than men but demonstrated better survival. Each scale except the frailty phenotype demonstrated an upper limit to frailty below the scale's theoretical maximum. Across commonly used frailty scales, these characteristics are common in nature but differ in magnitude.
Successfully Reducing Antibiotic Prescribing in Nursing Homes
Authors: Zimmerman Sheryl , Sloane Philip D. , Bertrand Rosanna , Olsho Lauren E. W. , Beeber Anna , Kistler Christine , Hadden Louise , Edwards Alrick , Weber David J. , Mitchell C. Madeline 
Published: April 2014

ObjectivesTo determine whether antibiotic prescribing can be reduced in nursing homes using a quality improvement (QI) program that involves providers, staff, residents, and families.DesignA 9‐month quasi‐experimental trial of a QI program in 12 nursing homes (6 comparison, 6 intervention) conducted from March to November 2011.SettingNursing homes in two regions of North Carolina, roughly half of whose residents received care from a single practice of long‐term care providers.ParticipantsAll residents, including 1,497 who were prescribed antibiotics.InterventionIn the intervention sites, providers in the single practice and nursing home nurses received training related to prescribing guidelines, including situations for which antibiotics are generally not indicated, and nursing home residents and their families were sensitized to matters related to antibiotic prescribing. Feedback on prescribing was shared with providers and nursing home staff monthly.MeasurementsRates of antibiotic prescribing for presumed urinary tract, skin and soft tissue, and respiratory infections.ResultsThe QI program reduced the number of prescriptions ordered between baseline and follow‐up more in intervention than in comparison nursing homes (adjusted incidence rate ratio = 0.86, 95% confidence interval = 0.79–0.95). Based on baseline prescribing rates of 12.95 prescriptions per 1,000 resident‐days, this estimated adjusted incidence rate ratio implies 1.8 prescriptions avoided per 1,000 resident‐days.ConclusionThis magnitude of effect is unusual in efforts to reduce antibiotic use in nursing homes. Outcomes could be attributed to the commitment of the providers; outreach to providers and staff; and a focus on common clinical situations in which antibiotics are generally not indicated; and suggest that similar results can be achieved on a wider scale if similar commitment is obtained and education provided.
Up‐regulation of the chemo‐attractive receptor ChemR23 and occurrence of apoptosis in human chondrocytes isolated from fractured calcaneal osteochondral fragments
Authors: Sena Paola , Manfredini Giuseppe , Benincasa Marta , Mariani Francesco , Smargiassi Alberto , Catani Fabio , Palumbo Carla 
Published: April 2014

AbstractTo study the expression level of a panel of pro/anti‐apoptotic factors and inflammation‐related receptors in chondral fragments from patients undergoing surgical treatment for intra‐articular calcaneal fractures, cartilage fragments were retrieved from calcaneal fractures of 20 patients subjected to surgical treatment. Primary cultures were performed using chondral fragments from fractured and control patients. Chondrocyte cultures from each patient of the fractured and control groups were subjected to immunofluorescence staining and quantitatively analyzed under confocal microscopy. Proteins extracted from the cultured chondrocytes taken from the fractured and control groups were processed for Western blot experiments and densitometric analysis. The percentage of apoptotic cells was determined using the cleaved PARP‐1 antibody. The proportion of labelled cells was 35% for fractured specimens, compared with 7% for control samples. Quantification of caspase‐3 active and Bcl‐2 proteins in chondrocyte cultures showed a significant increase of the apoptotic process in fractured specimens compared with control ones. Fractured chondrocytes were positively stained for ChemR23 with statistically significant differences with respect to control samples. Densitometric evaluation of the immunoreactive bands confirmed these observations. Human articular chondrocytes obtained from patients with intra‐articular calcaneal fractures express higher levels of pivotal pro‐apoptotic factors, and of the chemo‐attractive receptor ChemR23, compared with control cultures. On the basis of these observations, the authors hypothesize that consistent prolonged chondrocyte death, associated with the persistence of high levels of pro‐inflammatory factors, could enhance the deterioration of cartilage tissue with consequent development of post‐traumatic arthritis following intra‐articular bone fracture.
Mutational analysis of FOXL2 p.C134W and expression of bone morphogenetic protein 2 in Japanese patients with granulosa cell tumor of ovary
Authors: Oseto Kumiko , Suzumori Nobuhiro , Nishikawa Ryutaro , Nishikawa Hiroshi , Arakawa Atsushi , Ozaki Yasuhiko , Asai Hidekazu , Kawai Michiyasu , Mizuno Kimio , Takahashi Satoru , Shirai Tomoyuki , Yamada‐Namikawa Chisato , Nakanishi Makoto , Kajiyama Hiroaki , Kikkawa Fumitaka , Sugiura‐Ogasawara Mayumi 
Published: April 2014

AbstractAimTo assess whether FOXL2 p.C134W mutation may play a role in the development of human ovarian tumors in the Japanese, we investigated the FOXL2 codon 134 mutation and protein expression of inhibin‐α, bone morphogenetic protein 2 (BMP2) and follistatin (FST) in Japanese patients with granulosa cell tumor (GCT) of the ovary and other ovarian tumors.MethodsWe analyzed 114 tumor tissues from ovarian tumors, including 44 adult‐type and two juvenile‐type GCT of the ovary and 68 ovarian tumors by DNA sequencing. Immunohistochemistry was also performed in the adult and juvenile GCT tissues by immunostaining inhibin‐α, BMP2 and FST.ResultsWe found the FOXL2 p.C134W mutation in 27 out of 44 (61.4%) adult‐type GCT of the ovary, but none in other ovarian tumors. Histologically, all of the adult‐type GCT sections were positive for inhibin‐α, and the expression of BMP2 and FST was detected in 14 of 44 (31.8%) and zero of 47 (0%), respectively. No significant differences regarding the diagnosed age, preoperative serum carbohydrate antigen 125 levels, or BMP2 immunopositivity between the FOXL2 p.C134W mutation‐positive and mutation‐negative were found in the adult‐type GCT patients.ConclusionOur findings suggest that FOXL2 p.C134W mutation‐positive adult‐type GCT of the ovary may not be common in the Japanese as compared to the previous data.
Heat shock protein 70 is involved in malignant behaviors and chemosensitivities to cisplatin in cervical squamous cell carcinoma cells
Authors: Yoshidomi Keiko , Murakami Akihiro , Yakabe Kazuyuki , Sueoka Kotaro , Nawata Shugo , Sugino Norihiro 
Published: April 2014

AbstractAimHeat shock protein 70 (HSP70) was previously found to be highly expressed in cervical squamous cell carcinoma (SCC) tissues compared with normal tissues by proteomic analyses. The present study investigated the roles of HSP70 in malignant behaviors and chemosensitivity to cisplatin in cervical SCC cells in vitro.MethodsEffects of HSP70 knockdown on activities of cell migration, cell invasion and cell proliferation, cell cycle status, and apoptosis were examined using siRNA in two human cervical cancer cells (SiHa and SKG II). Furthermore, the effect of HSP70 knockdown on the apoptotic effect by cisplatin was examined.ResultsHSP70 knockdown significantly suppressed activities of cell migration, cell invasion and cell proliferation. The cell cycle was arrested at the S‐ and G2/M‐phases with the increase in apoptosis by HSP70 knockdown. Although cisplatin had no apoptotic effect in the control cell, it showed a dose‐dependent apoptotic effect in the HSP70 knockdown cells in SiHa. In SKG II, 5 μg/mL of cisplatin induced apoptosis, and the apoptotic effect by cisplatin was enhanced by HSP70 knockdown.ConclusionIt was suggested that HSP70 played functional roles in the progression of uterine cervical SCC, and HSP70 knockdown enhanced chemosensitivities to cisplatin in cervical SCC cells.
Association of functional polymorphisms in FAS and FASLigand genes promoter with pre‐eclampsia
Authors: Salimi Saeedeh , Moudi Bita , Farajian Mashhadi Farzaneh , Tavilani Heidar , Hashemi Mohammad , Zand Hamid , Yaghmaei Minoo 
Published: April 2014

AbstractAimPre‐eclampsia (PE) is a complex disorder of pregnancy with unknown etiology. FAS‐mediated apoptosis is assumed to prevent the development of PE; therefore FAS and FAS Ligand may be represented as candidate genes involved in PE pathogenesis. In the present study, we evaluated the relation between FAS Ligand A‐670G (rs1800682) and FAS Ligand C‐844T (rs763110) gene polymorphisms with PE in southeast Iran.MethodsOne hundred and twenty‐seven unrelated women with PE and 139 healthy control subjects were genotyped for the FAS A‐670G and FAS Ligand C‐844T polymorphisms by polymerase chain reaction restriction fragment length polymorphism method.ResultsThe AA, AG and GG genotype frequency of the FAS A‐670G polymorphism were 21.3%, 53.5% and 25.2% in pre‐eclamptic women and 46.0%, 41.5% and 11.5% in controls and were statistically different (P = 0.0001). The risk of PE was 2.7‐ and 4.7‐fold higher in pregnant women with AG and GG genotypes respectively. Although the frequency TT genotype and T allele of FAS Ligand C‐844T gene polymorphism was higher in the PE group, the differences were not significant.ConclusionFAS A‐670G polymorphism is associated with a higher risk for PE. There was no association between FAS Ligand C‐844T polymorphism and PE.
Safety of less aggressive surgery for stage IA1 squamous cell carcinoma of the cervix
Authors: Lee Jung‐Yun , Kim Hee Seung , Kim Kidong , Chung Hyun Hoon , Kim Jae Weon , Park Noh Hyun , Song Yong‐Sang 
Published: April 2014

AbstractAimTo determine the risk of extracervical disease in patients with stage IA1 squamous cell carcinoma of the cervix.MethodsA retrospective analysis was performed of 169 patients who had stage IA1 cervical cancer after conization at Seoul National University Hospital between 1997 and 2007.ResultsDuring the study period, 18 patients had conization as a definite treatment and 151 underwent subsequent surgery ranging from simple hysterectomy to radical hysterectomy with lymphadenectomy. Of the 151 patients who underwent subsequent surgery following conization, 35 (23.3%) patients underwent a simple hysterectomy, 20 (13.1%) a simple hysterectomy with pelvic lymphadenectomy and 96 (63.6%) radical surgery with lymphadenectomy. No parametrial involvement or lymph node metastasis was noted in any of the patients who underwent parametrial resection and/or lymphadenectomy. Of the 62 patients who had negative resection margins in conization specimens, only one presented with residual tumor in subsequent surgery. One recurrence of the disease was identified in the total sample (169 patients) with a median follow‐up time of 99 months.ConclusionThe risk of extracervical disease following conization is negligible, even for patients with positive resection margins in conization specimens. A more conservative and less aggressive approach may be possible for this patient subset.
Factors contributing to mortality and morbidity in pregnancy‐associated intracerebral hemorrhage in Japan
Authors: Yoshimatsu Jun , Ikeda Tomoaki , Katsuragi Shinji , Minematsu Kazuo , Toyoda Kazunori , Nagatsuka Kazuyuki , Naritomi Hiroaki , Miyamoto Susumu , Iihara Koji , Yamamoto Haruko , Ohno Yasumasa 
Published: April 2014

AbstractAimThe aim of this study was to analyze the causes and outcomes for intracerebral hemorrhage (ICH) occurring during pregnancy and postnatally.Material and MethodsA nationwide study of pregnancy‐related ICH in Japan was performed. We contacted 1582 facilities to identify women with ICH in pregnancy or postnatally between 1 January 2006 and 31 December 2006. A total of 1012 facilities (70%) responded with completed questionnaires. Risk factors for ICH, neurological features, onset to diagnosis time (O–D time), and obstetric data were recorded.ResultsThirty‐eight cases of pregnancy‐associated ICH were identified, corresponding to 3.5 per 100 000 deliveries. There were seven maternal deaths, giving a case mortality rate of 18.4%. Pre‐eclampsia was identified in 10 cases (26.3%) and hemolysis elevated liver enzymes and low platelet count (HELLP) syndrome was present in five. There were four cases (10.5%) with Moyamoya disease and seven (18.4%) with arteriovenous malformation. HELLP syndrome and moderately or severely disturbed consciousness at disease onset were significantly associated with a poor outcome (modified Rankin Scale ≥3). Pre‐eclampsia, HELLP syndrome and O–D time >3 h were significantly associated with maternal mortality.ConclusionEarly diagnosis may prevent maternal death, even in severe cases of pregnancy‐related ICH. However, maternal–fetal care centers do not always have full‐time neurosurgeons or diagnostic imaging tools suitable for diagnosis of ICH. Thus, a network should be established between maternity centers and neurosurgery departments with computed tomography or magnetic resonance imaging available at all times. We recommend transferal of pregnant women with neurological symptoms to a regional facility that is equipped to treat such patients.
Age‐specific cost and public funding of a live birth following assisted reproductive treatment in Japan
Authors: Maeda Eri , Ishihara Osamu , Saito Hidekazu , Kuwahara Akira , Toyokawa Satoshi , Kobayashi Yasuki 
Published: April 2014

AbstractAimThe aim of this study was to calculate and assess the cost of assisted reproductive technology (ART) treatment cycles and live‐birth events in Japan in 2010.Material and MethodsWe performed a retrospective analysis of 238 185 ART cycles, registered with the national registry of assisted reproductive treatment during 2010. Costs were calculated, using a decision analysis model.ResultsThe average cost per live birth was ¥1 974 000. This varied from ¥1 155 000 in women aged < 30 years to ¥50 189 000 in women aged ≥ 45, which was 29.6 times higher than that of women aged 35–39 years. This rose sharply in the early 40s and upwards. Public funding per live birth was ¥442 000. This was ¥6 118 000 in women aged ≥ 45, 15.4 times higher than that of the 35–39‐year‐old age group.ConclusionsThe costs and public funding of a live birth after ART treatment rises with age due to the lower success rates in older women. It may provide economic background to improve the current subsidy system for ART and to provide practical knowledge about fertility for the general population.
Absence of nonprimate hepacivirus‐related genomes in blood donors seroreactive for hepatitis C virus displaying indeterminate blot patterns
Authors: Levi J. E. , Cabral S. P. N. , Nishiya A. , Ferreira S. , Romano C. M. , Polite M. B. C. , Pereira R. A. A. , Mota M. A. , Kutner J. M. 
Published: April 2014

SummaryDespite intensive search, no primate homologue to the Hepatitis C Virus (HCV) has ever been found. The search for a zoonotic origin for HCV has been renewed recently when a virus, now known as non‐primate hepacivirus (NPHV), with a high homology to HCV was found in dogs. A variable proportion of anti‐HCV reactive blood donors submitted to the immunoblot (IB) to confirm their HCV status, present indeterminate results. The degree of homology between HCV and NPHV suggests that humans may be infected by NPHV or NPHV‐like viruses. Maximum similarity between NHPV and HCV is observed in the nonstructural regions 3 and 5. Peptides representing both domains are present in IB assays, so it is reasonable to suppose that blood donors harboring such viruses may display cross‐reactivity to the HCV antigenic fractions. Fifty‐nine plasma samples from blood donors found reactive for anti‐HCV and presenting IB indeterminate results were submitted to five distinct PCR reactions under low‐stringency conditions, employing primers targeting GBV‐C 5'UTR and NS3, Flavivirus‐genus NS5 and NPHV 5'UTR and NS3. No amplification was obtained with all primer pairs tested except for five samples that amplified both 5'UTR and NS3 fragments from GBV‐C. Unbiased next‐generation sequencing may prove or rule out the existence of HCV‐related viruses in IB indeterminate samples.
Immediate Effect of Passive Smoking on Microcirculatory Flow
Authors: Henriksson Peter , Lu Qing , Diczfalusy Ulf , Freyschuss Anna 
Published: April 2014

AbstractObjectiveExposure to SHS, as by passive smoking, seems to increase the incidence of cardiovascular events. It has been shown that active smoking of a single cigarette causes an immediate and significant decrease in microcirculatory blood flow velocity, whereas the acute effects of exposure to SHS on microcirculatory flow have as yet not been demonstrated.MethodsHealthy nonsmoking volunteers of both genders were studied during acute exposure to SHS of two cigarettes burning up to 10 minutes. Microvessels were examined by in vivo vital capillaroscopy (Capiflow®), allowing continuous assessment of CBV.ResultsCBV decreased from 514 mm/sec (CI 383–646) at baseline to 306 mm/sec (CI 191–420) at end of SHS exposure with a further decrease to a nadir of 240 mm/sec (CI 155–325) four minutes after the end of this exposure (p < 0.0001; ANOVA).ConclusionsThe result of this study shows that passive inhalation of secondhand cigarette smoke induces an immediate and prolonged marked reduction in CBV in nonsmoking healthy volunteers.