bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partial agonists for α4β2 nicotinic receptors stimulate dopaminergic neuron firing with relatively enhanced maximal effects
Authors: Chen Ying , Broad Lisa M , Phillips Keith G , Zwart Ruud 
Published: August 2011

BACKGROUND AND PURPOSE Partial agonists selective for α4β2 nicotinic ACh receptors have been developed for smoking cessation as they induce weak activation of native α4β2* receptors and inhibit effect of nicotine. However, it is unclear whether at brain functions there is an existence of receptor reserve that allows weak receptor activation to induce maximum physiological effects. We assessed the extent of α4β2 partial agonist‐induced increase of firing rate in dopaminergic neurons and evaluated the influence of receptor reserve.EXPERIMENTAL APPROACH The relative maximal effects and potencies of six nicotinic agonists were assessed on recombinant human α4β2 and α7 receptors expressed in mammalian cell lines by measuring calcium influx. Agonist‐induced increase of the spontaneous firing rate of dopaminergic neurons was recorded using microelectrodes in the ventral tegmental area of rat brain slices.KEY RESULTS All α4β2 partial and full agonists increased the firing rate concentration‐dependently. Their sensitivity to subtype‐selective antagonists showed predominant activation of native α4β2* receptors. However, partial agonists with relative maximal effects as low as 33% on α4β2 receptors maximally increased the firing rate and induced additional depolarization block of firing, demonstrating that partial activation of receptors caused the maximum increase in firing rate in the presence of a receptor reserve.CONCLUSIONS AND IMPLICATIONS Partial α4β2 agonists induced relatively enhanced effects on the firing rate of dopaminergic neurons, and the effect was mainly attributed to the existence of native α4β2* receptor reserve. The results have implications in the understanding of physiological effects and therapeutic efficacies of α4β2 partial agonists.
PLOD2 induced under hypoxia is a novel prognostic factor for hepatocellular carcinoma after curative resection
Authors: Noda Takehiro , Yamamoto Hirofumi , Takemasa Ichiro , Yamada Daisaku , Uemura Mamoru , Wada Hiroshi , Kobayashi Shogo , Marubashi Shigeru , Eguchi Hidetoshi , Tanemura Masahiro , Umeshita Koji , Doki Yuichro , Mori Masaki , Nagano Hiroaki 
Published: August 2011

AbstractBackgroundUnder hypoxia, tumour cells undergo genetic and adaptive changes that allow their survival. Previously, we reported that high expression of hypoxia‐inducible factor (HIF)‐1 was a significant predictive factor for recurrence in hepatocellular carcinoma (HCC). Hypoxia also stimulates expression of procollagen‐lysine, 2‐oxoglutarate 5‐dioxygenase (PLOD) genes via the HIF‐1 pathway.AimsThe aim was to evaluate the relationship between hypoxia stress and expression of PLOD genes in HCC in vitro and to identify a new prognostic marker in HCC patients.MethodsThe PLOD2 expression was assessed under hypoxia in hepatoma cell lines and characterized in 139 HCC samples following hepatic resection using microarray experiments, quantitative RT‐PCR and immunohistochemistry. Prognostic factors in HCC patients were assessed using univariate and multivariate analyses.ResultsThe PLOD2 expression was induced under the hypoxia in vitro. Disease‐free survival in the high PLOD2 expression group of HCC patients was significantly shorter when compared with the low‐expression group (P = 0.002). In a subset of HCCs, we found that the PLOD2 expression of microarray was correlated with data of quantitative RT‐PCR and immunohistochemistry. Of clinicopathological factors, PLOD2 expression was significantly correlated with tumour size (P = 0.022) and macroscopic intrahepatic metastasis (P = 0.049). In univariate analysis, six prognostic factors (tumour multiplicity, macroscopic intrahepatic metastasis, histological grade, microscopic portal invasion, microscopic intrahepatic metastasis and PLOD2 expression) were significant for disease‐free survival. PLOD2 expression was identified as a significant, independent factor of poor prognosis (P = 0.013).ConclusionsPLOD2 is a potential novel prognostic factor for HCC patients following surgery.
Does online hemodiafiltration lead to reduction in trace elements and vitamins?
Authors: CROSS Jennifer , DAVENPORT Andrew 
Published: August 2011

AbstractHemodiafiltration (HDF) has been reported to improve nutritional intake, but as it increases convective losses, it could also increase micronutrient loss. We prospectively audited the effect of HDF on vitamin B12, zinc and selenium. Thirty‐four patients dialyzing (T/Th/Sa) switched to HDF, and 44 dialyzing (M/W/F) remained on high‐flux hemodialysis (HD) and were followed for 12 months. Dialysis adequacy, weight, hemoglobin, and serum albumin did not differ between the groups and did not change over 12 months’ follow up. Similarly, vitamin B12 did not differ: HDF, 443 (325–682) ng/mL HD vs. 478 (327–690) ng/mL HDF; 6 months, 513 (351–664) ng/mL vs. 460 (379–647) ng/mL; or 12 months, 444 (317–617) ng/mL vs. 492 (323–644) ng/mL. And no patient had subnormal values. Folate levels, in those not taking supplements, were also stable (start, 6.2 ± 0.7 μg/L HD vs. 7.2 ± 1.0 μg/L HDF; 12 months, 6.5 ± 0.9 μg/L vs. 10.9 ± 2.4 μg/L). Serum zinc was subnormal in 50% prior to switching to HDF, 10.4 ± 0.4 μmol/L, but did not fall with HDF 10.2 ± 0.3 μmol/L; similarly, selenium was low in 49% prior to switching to HDF, 0.77 ± 0.06 μmol/L, but remained stable on HDF, 0.82 ± 0.06 μmol/L. Although HDF adds convective clearance to standard hemodialysis, it does not lead to a reduction in vitamin B12, folate, zinc, or selenium. However, half of this dialysis cohort had low levels of both zinc and selenium.
Massive, painful tumoral calcinosis in a long‐term hemodialysis patient
Authors: CARVALHO Mauricio , de MENEZES Igor Alexandre Côrtes , RIELLA Miguel Carlos 
Published: August 2011

AbstractIn chronic dialysis patients, ectopic, extraosseous calcifications can cause significant morbidity. Uremic tumoral calcinosis is an uncommon and severe complication of dialysis therapy. It is defined as deposition of dense nodular calcium‐containing masses surrounding the large joints of the body, generally associated with the presence of high serum calcium‐and‐phosphorus product. We describe a 69‐year‐old woman submitted to long‐term chronic hemodialysis that developed painful, bilateral hip tumors. Radiographic investigation showed extensive periarticular calcifications, and a bone biopsy was suggestive of adynamic bone disease and contained substantial amounts of aluminum. The lesions were surgically excised, and the histological analysis demonstrated amorphous, calcified material associated with densely collagenized connective tissue.
Hemodialysis catheter infection with unusual presentation and grave outcome
Authors: GABALDON Darlene , XU Zhi , SUN Yijuan , SERVILLA Karen S. , HARTSHORNE Michael F. , TZAMALOUKAS Antonios H. 
Published: August 2011

AbstractBacteremia from central venous catheter (CVC) infection causes morbidity and mortality in patients on hemodialysis (HD). Diagnosis of the infection can be difficult and may require special imaging. A 70‐year‐old man with diabetic nephropathy was on HD for 11 months through a permanent CVC. Because of symptomatic osteoporosis, he had kyphoplasty in three lumbar vertebrae (L2, L3, L4) 6 months after starting HD. Severe back pain persisted after kyphoplasty. Throughout the HD period, the exit site of the CVC had a clean appearance, there was no fever, and blood leukocyte counts were normal. During the 11th month of HD, he complained of subjective fever at home. Blood count revealed normal leukocyte count with neutrophilic predominance and blood cultures grew methicillin‐resistant Staphylococcus aureus (MRSA). Echocardiogram revealed no heart valve vegetations, but irregular thickening of the CVC wall. Fluorodeoxyglucose positron‐emission tomography‐computed tomography (FDG‐PET‐CT) revealed severe inflammation of the CVC wall and a picture consistent with osteomyelitis and severe destruction of the body of the 11th thoracic vertebra. He was treated with intravenous vancomycin and removal of the CVC, the wall of which was grossly inflamed and grew in culture MRSA. Three weeks later, he discontinued HD because of persistent severe back pain. CVC infection with bacteremia and remote infectious foci having grave sequelae can develop in HD patients with paucity of clinical manifestations. FDG‐PET‐CT is a useful imaging tool in establishing the presence and extent of both the CVC infection and remote metastatic infectious foci.
Psychiatric diagnosis in late adolescence and long‐term risk of suicide and suicide attempt
Authors: Lundin A. , Lundberg I. , Allebeck P. , Hemmingsson T. 
Published: August 2011

Lundin A, Lundberg I, Allebeck P, Hemmingsson T. Psychiatric diagnosis in late adolescence and long‐term risk of suicide and suicide attempt.Objective:  To investigate the associations between psychiatric diagnosis in late adolescence in an unselected population and subsequent suicide attempt and suicide during 36‐year follow‐up.Method:  A total of 49 321 Swedish men conscripted for compulsory military training in 1969/1970, born 1949–1951, were screened for psychiatric disorder and, if detected, diagnosed by a psychiatrist according to ICD‐8. Data on suicides and suicide attempts 1971–2006 were collected in national registers.Results:  At conscription examination, 11.7% of the cohort received a psychiatric diagnosis. Among those, increased risks of suicide 1971–2006 [HR = 2.7 (2.2–3.2), 624 cases] and suicide attempt 1973–2006 [HR = 3.5 (3.1–4.0), 1170 cases] were found. The increased relative risks persisted during the follow‐up period 19–36 years after examination [1989–2006 suicide HR = 2.1 (1.6–2.7), 308 cases, and 1989–2006 suicide attempt HR = 2.6 (2.1–3.1), 484 cases]. The dominant diagnostic groups, neurosis and personality disorder, were significantly associated with suicide and suicide attempt in the early as well as the late follow‐up period.Conclusion:  Psychiatric diagnoses made in late adolescence predicted subsequent suicide and suicide attempt over a 36‐year follow‐up period. The increased relative risks were not limited to young adulthood but were also evident 18–36 years after conscription examination.
The oral microbiome in health and disease and the potential impact on personalized dental medicine
Authors: Zarco MF , Vess TJ , Ginsburg GS 
Published: August 2011

Oral Diseases (2012) 18, 109–120Every human body contains a personalized microbiome that is essential to maintaining health but capable of eliciting disease. The oral microbiome is particularly imperative to health because it can cause both oral and systemic disease. The oral microbiome rests within biofilms throughout the oral cavity, forming an ecosystem that maintains health when in equilibrium. However, certain ecological shifts in the microbiome allow pathogens to manifest and cause disease. Severe forms of oral disease may result in systemic disease at different body sites. Microbiomics and metagenomics are two fields of research that have emerged to identify the presence of specific microbes in the body and understand the nature of the microbiome activity during both health and disease. The analysis of the microbiome and its genomes will pave the way for more effective therapeutic and diagnostic techniques and, ultimately, contribute to the development of personalized medicine and personalized dental medicine.
Is Peripheral Blood Cell Balanced Altered by the Use of Fresh Frozen Bone Block Allografts in Lateral Maxillary Ridge Augmentation?
Authors: Spin Neto Rubens , Felipe Leite Coletti , Pereira Luis Antonio Violin Dias , Marcantonio Elcio , Marcantonio Jr Elcio 
Published: August 2011

ABSTRACTBackground: The relationship between the immune response and red and white blood cell homeostasis is cited in literature, but no studies regarding the balance of these cell populations following maxillary bone‐graft surgeries can be found.Aim: The aim of this study was to evaluate the possible impairments in the blood cell balance following fresh–frozen allogeneic bone‐graft augmentation procedures in patients who needed maxillary reconstruction prior to implants.Material and Methods: From 33 patients elected to onlay bone grafting procedures, 20 were treated with fresh–frozen bone allografts and 13 with autologous bone grafts. Five blood samples were collected from each patient in a 6‐month period (baseline: 14, 30, 90, and 180 days postsurgery), and the hematological parameters (erythrogram, leukogram, and platelets count) were accessed.Results: All evaluated parameters were within the reference values accepted as normal, and significant differences were found for the eosinophils count when comparing the treatments (30 days, p = .035) and when comparing different periods of evaluation (allograft‐treated group, baseline × 180 days, p ≤ .05 and 90 × 180 days, p ≤ .01; autograft‐treated group, 30 × 90 days, p ≤ .05 and 30 × 180 days, p ≤ .05).Conclusions: Both autologous and fresh–frozen allogeneic bone grafts did not cause any impairment in the red and white blood cell balance, based on quantitative hemogram analysis, in patients subjected to maxillary reconstruction.
Improved Sexual Function with Testosterone Replacement Therapy in Hypogonadal Men: Real-World Data from the Testim Registry in the United States (TRiUS)
Authors: Khera Mohit , Bhattacharya Rajib K. , Blick Gary , Kushner Harvey , Nguyen D.t. , Miner Martin M. 
Published: August 2011

ABSTRACT

Introduction
Up to 30% of erectile dysfunction (ED) patients treated with phosphodiesterase type 5 (PDE5) inhibitors do not show improved sexual function, which may be due in part to low serum testosterone. Hypogonadal patients already receiving testosterone replacement therapy (TRT) likewise can still suffer from symptoms of sexual dysfunction. In these patient populations, augmenting with, or switching, TRT treatment may improve sexual function.

Aim
To determine if 12-month treatment with a testosterone gel improves sexual function in hypogonadal men, as measured by the Brief Male Sexual Function Inventory (BMSFI), and in subgroups defined by low testosterone, PDE5 inhibitor use, and prior TRT.

Methods
The Testim Registry in the United States (TRiUS) was a large (N = 849) multicenter registry of hypogonadal men treated with Testim (testosterone 1%) topical gel and followed for 12 months.

Main Outcome Measures
Data collected at suggested visits (baseline; 1, 3, 6, and 12 months) included total testosterone (TT), free testosterone (FT), BMSFI scores, physical exam, and body measurements.

Results
TRiUS had 271 patients with baseline testosterone and BMSFI measurements. At 12 months of TRT, TT and FT levels significantly increased from baseline (P &lt; 0.001), with mean ± standard deviation final TT = 17.37 ± 8.61 nmol/L (500.6 ± 248.2 ng/dL) and FT = 240.1 ± 296.0 pmol/L (69.2 ± 85.3 pg/mL). The mean total BMSFI score significantly increased from baseline at 12 months (27.4 ± 10.3 to 33.8 ± 9.8, P &lt; 0.001) and at each visit in all domains (sex drive/libido, erectile function, ejaculatory function, level of bother), overall and for all subgroups. Regression analysis indicated that increased total BMSFI score was significantly associated with increased TT levels at 6 months.

Conclusions
In hypogonadal patients, 12-month administration of topical testosterone gel resulted in increased TT and FT levels and significantly improved sexual function. All subgroups studied, including men taking PDE5 inhibitors for ED and those previously on TRT, demonstrated significant improvement in sexual function from baseline scores.
Women's Bike Seats: A Pressing Matter for Competitive Female Cyclists
Authors: Guess Marsha K. , Partin Sarah N. , Schrader Steven , Lowe Brian , LaCombe Julie , Reutman Susan , Wang Andrea , Toennis Christine , Melman Arnold , Mikhail Madgy , Connell Kathleen A. 
Published: August 2011

ABSTRACTIntroductionThere are numerous genital complaints in women cyclists, including pain, numbness, and edema of pelvic floor structures. Debate ensues about the best saddle design for protection of the pelvic floor.AimTo investigate the relationships between saddle design, seat pressures, and genital nerve function in female, competitive cyclists.MethodsWe previously compared genital sensation in healthy, premenopausal, competitive women bicyclists and runners. The 48 cyclists from our original study comprise the study group in this subanalysis.Main Outcome MeasuresMain outcome measures were: (i) genital vibratory thresholds (VTs) determined using the Medoc Vibratory Sensation Analyzer 3000 and (ii) saddle pressures as determined using a specially designed map sensor.ResultsMore than half of the participants (54.8%) used traditional saddles, and the remainder (45.2%) rode with cut-out saddles. On bivariate analysis, use of traditional saddles was associated with lower mean perineal saddle pressures (MPSP) than riding on cut-out saddles. Peak perineal saddle pressures (PPSP) were also lower; however, the difference did not reach statistical significance. Saddle design did not affect mean or peak total saddle pressures (MTSP, PTSP). Saddle width was significantly associated with PPSP, MTSP, and PTSP but not with MPSP. Women riding cut-out saddles had, on average, a 4 and 11 kPa increase in MPSP and PPSP, respectively, compared with women using traditional saddles (P = 0.008 and P = 0.010), after adjustment for other variables. Use of wider saddles was associated with lower PPSP and MTSP after adjustment. Although an inverse correlation was seen between saddle pressures and VTs on bivariate analysis, these differences were not significant after adjusting for age.ConclusionCut-out and narrower saddles negatively affect saddle pressures in female cyclists. Effects of saddle design on pudendal nerve sensory function were not apparent in this cross-sectional analysis. Longitudinal studies evaluating the long-term effects of saddle pressure on the integrity of the pudendal nerve, pelvic floor, and sexual function are warranted.
Relationship between reduced lower abdominal blood flows and heart rate in recovery following cycling exercise
Authors: Osada T. , Iwane H. , Katsumura T. , Murase N. , Higuchi H. , Sakamoto A. , Hamaoka T. , Shimomitsu T. 
Published: August 2011

Abstract
Aim:  To examine the blood flow (BF) response in the lower abdomen (LAB) in recovery following upright cycling exercise at three levels of relative maximum pulmonary oxygen consumption () and the relationship of BFLAB to heart rate (HR) and target intensity.
Methods:  For 11 healthy subjects, BF (Doppler ultrasound) in the upper abdominal aorta (Ao) above the coeliac trunk and in the right femoral artery (RFA) was measured repeatedly for 720 s after the end of cycling exercises at target intensities of 30%, 50% and 85%, respectively. Blood flow in the lower abdomen (BFLAB) can be measured by subtracting bilateral BFFAs (≈twofolds of BFRFA) from BFAo. Change in BFLAB (or BFLAB volume) at any point was evaluated by difference between change in BFAo and in BFFAs. Heart rate and blood pressure were also measured.
Results:  At 85%, significant reduction in BFLAB by approx. 89% was shown at 90 s and remained until 360 s. At 50%, reduction in BFLAB by approx. 33% was found at 90 s although it returned to pre‐exercise value at 120 s. On the contrary at 30%, BFLAB showed a light increase (<20%) below 70 bpm of HR. There was a close negative relationship (P < 0.05) between change in BFLAB and recovery HR, as well as between change in BFLAB volume and both recovery HR and %.
Conclusion:  This study suggests that the lower abdominal BF in recovery may be influenced by sympathetic‐vagus control, and dynamics of BFLAB may be closely related to the level of relative exercise intensities.
Wheat Germ Agglutinin Modified Liposomes for the Photodynamic Inactivation of Bacteria†
Authors: Yang Kewei , Gitter Burkhard , Rüger Ronny , Albrecht Volker , Wieland Gerhard D. , Fahr Alfred 
Published: August 2011

AbstractPhotodynamic inactivation (PDI) of bacteria is a promising approach for combating the increasing emergence of antibiotic resistance in pathogenic bacteria. To further improve the PDI efficiency on bacteria, a bacteria‐targeting liposomal formulation was investigated. A generation II photosensitizer (temoporfin) was incorporated into liposomes, followed by conjugation with a specific lectin (wheat germ agglutinin, WGA) on the liposomal surface. WGA was successfully coupled to temoporfin‐loaded liposomes using an activated phospholipid containing N‐hydroxylsuccinimide residue. Methicillin‐resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were selected to evaluate the WGA modified liposomes in terms of bacteria targeted delivery and in vitro PDI test. Fluorescence microscopy revealed that temoporfin was delivered to both kinds of bacteria, while flow cytometry demonstrated that WGA‐ modified liposomes delivered more temoporfin to bacteria compared to nonmodified liposomes. Consequently, the WGA‐ modified liposomes eradicated all MRSA and significantly enhanced the PDI of P. aeruginosa. In conclusion, the WGA‐ modified liposomes are a promising formulation for bacteria targeted delivery of temoporfin and for improving the PDI efficiency of temoporfin on both Gram‐positive and Gram‐negative bacterial cells.
An In Vitro Comparison of the Effects of the Iron‐Chelating Agents, CP94 and Dexrazoxane, on Protoporphyrin IX Accumulation for Photodynamic Therapy and/or Fluorescence Guided Resection
Authors: Blake Emma , Allen James , Curnow Alison 
Published: August 2011

AbstractPhotodynamic therapy (PDT) utilizes the combined interaction of a photosensitizer, light and molecular oxygen to ablate tumor tissue. Maximizing the accumulation of the photosensitizer protoporphyrin IX (PpIX) within different cell types would be clinically useful. Dermatological PpIX‐induced PDT regimes produce good clinical outcomes but this currently only applies when the lesion remains superficial. Also, as an adjuvant therapy for the treatment of primary brain tumors, fluorescence guided resection (FGR) and PDT can be used to highlight and destroy tumor cells unreachable by surgical resection. By employing iron chelators PpIX accumulation can be enhanced. Two iron‐chelating agents, 1,2‐diethyl‐3‐hydroxypyridin‐4‐one hydrochloride (CP94) and dexrazoxane, were individually combined with the porphyrin precursors aminolevulinic acid (ALA), methyl aminolevulinate (MAL) and hexyl aminolevulinate (HAL). Efficacies of the iron‐chelating agents were compared by recording the PpIX fluorescence in human squamous epithelial carcinoma cells (A431) and human glioma cells (U‐87 MG) every hour for up to 6 h. Coincubation of ALA/MAL/HAL with CP94 resulted in a greater accumulation of PpIX compared to that produced by coincubation of these congeners with dexrazoxane. Therefore the clinical employment of iron chelation, particularly with CP94 could potentially increase and/or accelerate the accumulation of ALA/MAL/HAL‐induced PpIX for PDT or FGR.