bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection against tuberculosis by a single intranasal administration of DNA-hsp65 vaccine complexed with cationic liposomes
Authors: Rosada Rogério S , Torre Lucimara Gaziola de la , Frantz Fabiani G , Trombone Ana PF , Zárate-Bladés Carlos R , Fonseca Denise M , Souza Patrícia RM , Brandão Izaíra T , Masson Ana P , Soares Édson G , Ramos Simone G , Faccioli Lúcia H , Silva Célio L , Santana Maria HA , Coelho-Castelo Arlete AM 
Published: July 2008

AbstractBackgroundThe greatest challenges in vaccine development include optimization of DNA vaccines for use in humans, creation of effective single-dose vaccines, development of delivery systems that do not involve live viruses, and the identification of effective new adjuvants. Herein, we describe a novel, simple technique for efficiently vaccinating mice against tuberculosis (TB). Our technique consists of a single-dose, genetic vaccine formulation of DNA-hsp65 complexed with cationic liposomes and administered intranasally.ResultsWe developed a novel and non-toxic formulation of cationic liposomes, in which the DNA-hsp65 vaccine was entrapped (ENTR-hsp65) or complexed (COMP-hsp65), and used to immunize mice by intramuscular or intranasal routes. Although both liposome formulations induced a typical Th1 pattern of immune response, the intramuscular route of delivery did not reduce the number of bacilli. However, a single intranasal immunization with COMP-hsp65, carrying as few as 25 μg of plasmid DNA, leads to a remarkable reduction of the amount of bacilli in lungs. These effects were accompanied by increasing levels of IFN-γ and lung parenchyma preservation, results similar to those found in mice vaccinated intramuscularly four times with naked DNA-hsp65 (total of 400 μg).ConclusionOur objective was to overcome the significant obstacles currently facing DNA vaccine development. Our results in the mouse TB model showed that a single intranasal dose of COMP-hsp65 elicited a cellular immune response that was as strong as that induced by four intramuscular doses of naked-DNA. This formulation allowed a 16-fold reduction in the amount of DNA administered. Moreover, we demonstrated that this vaccine is safe, biocompatible, stable, and easily manufactured at a low cost. We believe that this strategy can be applied to human vaccines to TB in a single dose or in prime-boost protocols, leading to a tremendous impact on the control of this infectious disease.
The function of Shp2 tyrosine phosphatase in the dispersal of acetylcholine receptor clusters
Authors: Qian Yueping K , Chan Ariel WS , Madhavan Raghavan , Peng H Benjamin 
Published: July 2008

Abstract

Background
A crucial event in the development of the vertebrate neuromuscular junction (NMJ) is the postsynaptic enrichment of muscle acetylcholine (ACh) receptors (AChRs). This process involves two distinct steps: the local clustering of AChRs at synapses, which depends on the activation of the muscle-specific receptor tyrosine kinase MuSK by neural agrin, and the global dispersal of aneural or "pre-patterned" AChR aggregates, which is triggered by ACh or by synaptogenic stimuli. We and others have previously shown that tyrosine phosphatases, such as the SH2 domain-containing phosphatase Shp2, regulate AChR cluster formation in muscle cells, and that tyrosine phosphatases also mediate the dispersal of pre-patterned AChR clusters by synaptogenic stimuli, although the specific phosphatases involved in this latter step remain unknown.

Results
Using an assay system that allows AChR cluster assembly and disassembly to be studied separately and quantitatively, we describe a previously unrecognized role of the tyrosine phosphatase Shp2 in AChR cluster disassembly. Shp2 was robustly expressed in embryonic Xenopus muscle in vivo and in cultured myotomal muscle cells, and treatment of the muscle cultures with an inhibitor of Shp2 (NSC-87877) blocked the dispersal of pre-patterned AChR clusters by synaptogenic stimuli. In contrast, over-expression in muscle cells of either wild-type or constitutively active Shp2 accelerated cluster dispersal. Significantly, forced expression in muscle of the Shp2-activator SIRPα1 (signal regulatory protein α1) also enhanced the disassembly of AChR clusters, whereas the expression of a truncated SIRPα1 mutant that suppresses Shp2 signaling inhibited cluster disassembly.

Conclusion
Our results suggest that Shp2 activation by synaptogenic stimuli, through signaling intermediates such as SIRPα1, promotes the dispersal of pre-patterned AChR clusters to facilitate the selective accumulation of AChRs at developing NMJs.
ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC) cells, and inhibits growth and vascularization in vivo
Authors: Moser Christian , Lang Sven A , Mori Akira , Hellerbrand Claus , Schlitt Hans J , Geissler Edward K , Fogler William E , Stoeltzing Oliver 
Published: July 2008

Abstract

Background
Hepatocellular carcinoma (HCC) represents a highly vascularized tumor entity and the process of angiogenesis is essential for the growth of HCC. Importantly, the pro-angiogenic transcription factors HIF-1α and STAT3 have been implicated in HCC progression, thus representing interesting targets for molecular targeted therapy. We hypothesized that therapeutic inhibition of HIF-1α could be achieved by using a novel tubulin-binding agent (ENMD-1198). ENMD-1198 is an analog of 2-methoxyestradiol (2ME2) with antiproliferative and antiangiogenic activity.

Methods
The human HCC cell lines HUH-7 and HepG2 were used for experiments. Effects of ENMD-1198 on constitutive and inducible (hypoxia, growth factors) activation of signaling cascades, including HIF-1α and STAT3, were investigated by Western blotting. Changes in VEGF expression were determined by real-time PCR. Effects of ENMD-1198 on cancer cell migration and invasion were evaluated in in vitro-assays. The growth-inhibitory effects of ENMD-1198 (200 mg/kg/day) were determined in a subcutaneous tumor model (HUH-7).

Results
ENMD-1198 inhibited the phosphorylation of MAPK/Erk, PI-3K/Akt and FAK. Moreover, activation of HIF-1α and STAT3 was dramatically reduced by ENMD-1198, which resulted in lower VEGF mRNA expression (P < 0.05). In addition, tumor cell migratory and invasive properties were significantly inhibited (P < 0.05, for both). In vivo, treatment with ENMD-1198 led to a significant reduction in tumor growth, tumor vascularization, and numbers of proliferating tumor cells (P < 0.05 for all).

Conclusion
The novel microtubule destabilizing agent ENMD-1198 is suitable for inhibiting HIF-1α and STAT3 in human HCC cells and leads to reduced tumor growth and vascularization in vivo. Hence, inhibition of HIF-1α and STAT3 could prove valuable for therapy of hepatocellular carcinoma.
Stress load during childhood affects psychopathology in psychiatric patients
Authors: Weber Katja , Rockstroh Brigitte , Borgelt Jens , Awiszus Barbara , Popov Tzvetan , Hoffmann Klaus , Schonauer Klaus , Watzl Hans , Pröpster Karl 
Published: July 2008

Abstract

Background
Childhood stress and trauma have been related to adult psychopathology in different psychiatric disorders. The present study aimed at verifying this relationship for stressful experiences during developmental periods by screening stress load across life in adult psychiatric inpatients with different diagnoses compared to healthy subjects. In addition, a relationship between the amount of adverse experiences and the severity of pathology, which has been described as a 'building block' effect in posttraumatic stress disorder (PTSD), was explored for non-traumatic events in psychiatric disorders other than PTSD.

Methods
96 patients with diagnoses of Major Depressive Disorder (MDD), schizophrenia, drug addiction, or personality disorders (PD) and 31 subjects without psychiatric diagnosis were screened for adverse experiences in childhood (before the age of six years), before onset of puberty, and in adulthood using the Early Trauma Inventory and the Posttraumatic Stress Diagnostic Scale. Effects of stress load on psychopathology were examined for affective symptoms, PTSD, and severity of illness by regression analyses and comparison of subgroups with high and low stress load.

Results
High stress load in childhood and before puberty, but not in adulthood, was related to negative affect in all participants. In patients, high stress load was related to depressive and posttraumatic symptoms, severity of disorder, and the diagnoses of MDD and PD.

Conclusion
Results support the hypothesis of stress-sensitive periods during development, which may interact with genetic and other vulnerability factors in their influence on the progress of psychiatric disorders. A 'dose' effect of stress load on the severity of psychopathology is not restricted to the relationship between traumata and PTSD.
Risk factors for bone mineral density at the calcaneus in 40–59 year-old male workers: A cross-sectional study in Korea
Authors: Seo Hyun-Ju , Kim Soo-Geun , Kim Chong-Soon 
Published: July 2008

Abstract

Background
Few epidemiologic studies have attempted to investigate the prevalence and risk factors for osteopenia and osteoporosis in middle-aged Asian men. We performed this study to determine the prevalence and risk factors of osteopenia and osteoporosis in this population.

Methods
This cross-sectional study was conducted from March to July, 2004. The subjects were 2,073 males aged from 40 to 59 years in the KHNP (Korea Hydro & Nuclear Power) workplace-based cohort. Bone mineral density (BMD) was measured by peripheral, dual-energy, X-ray absorptiometry (DXA) at the calcaneus. Anthropometric and lifestyle factors were investigated using a standard, self-reported questionnaire.

Results
BMD was 0.60 ± 0.09 g/cm2 (mean ± standard deviation) and was negatively correlated with age (r = -0.18, P < 0.001), but positively correlated with waist-to-hip ratio (WHR; r = 0.15, P < 0.001), body fat (r = 0.10, P < 0.001), BMI (r = 0.35, P < 0.001), height (r = 0.26, P < 0.001), and weight (r = 0.43, P < 0.001).
In multiple linear regression analysis, the independent determinants associated with BMD were increasing age (coefficient = -0.002, P < 0.001), physical activity (≤ 2/week vs. ≥ 3/week; coefficient = 0.017, P < 0.001), WHR (coefficient = -0.796, P < 0.001), body mass index (BMI; coefficient = 0.023, P < 0.001) and smoking status (never vs. ever; coefficient = -0.018, P < 0.001).

Conclusion
We suggest that BMD of the calcaneus is correlated negatively with exposure to smoke and increased WHR, but positively with regular exercise and increased BMI.
Role of Corticotropin-Releasing Hormone Testing in Assessment of Hypothalamic-Pituitary-Adrenal Axis Function in Infants with Congenital Central Hypothyroidism
Authors: van Tijn David A. , de Vijlder Jan J. M. , Vulsma Thomas 
Published: July 2008

Context: The Dutch neonatal congenital hypothyroidism (CH) screening program detects infants with CH of central origin (CH-C). These infants have a high likelihood of multiple pituitary hormone deficiencies. ACTH deficiency especially poses an additional risk for brain damage and may be fatal.
Objective: Our objective was to evaluate different tools for assessment of the integrity of the hypothalamus-pituitary-adrenocortex (HPA) axis in young infants, aiming for a strategy for reliable and timely diagnosis.
Design, Setting: This is a Dutch nationwide prospective study (enrollment 1994–1996). Patients were included if neonatal CH screening results were indicative of CH-C and HPA axis function could be tested within 6 months of birth.
Patients: Nine male and three female infants with CH-C and four infants with false-positive screening results or transient hypothyroidism were included in the study.
Main Outcome Measures: CRH test results, multiple cortisol plasma concentrations, and cortisol excretion in 24-h urine were measured.
Results: Six (50%) of the CH-C patients had abnormal CRH test results. Three of them had discordant test results: impaired increase of plasma cortisol in response to CRH, despite substantial increase of plasma ACTH. The other three infants, with concordant impaired responses of both ACTH and cortisol to CRH, had a very low urinary cortisol excretion in comparison with the subjects with normal CRH test results.
Conclusions: The CRH test proves to be a fast and reliable tool in the assessment of HPA axis (dys)function. It enables timely diagnosis in (asymptomatic) neonates at risk for serious morbidity and mortality. The discordant response type, which has not been described before, may be an early phase of HPA axis dysfunction. Alternatively, patients with this response type may constitute a separate pathogenetic subset of HPA axis-deficient patients.
Ramelteon: A Novel Approach in the Treatment of Insomnia
Authors: Reynoldson Jill N , Elliott Ellie SR , Nelson Leigh Anne 
Published: July 2008

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of ramelteon in the treatment of primary insomnia in adults, including elderly adults. Data Sources: MEDLINE (1966–July 2008) and PsyclNFO (1985–July 2008) literature searches were conducted to idontify clinical data involving ramelteon. The manufacturer provided a summary of clinical data and abstracts of unpublished studies. Study Selection And Data Extraction: All primary literature, including abstracts, focusing on the pharmacology and pharmacokinetics of ramelteon and clinical trials evaluating its use was reviewed. Information deemed most relevant was incorporated. Our search revealed 5 controlled trials evaluating the short-term efficacy and safety of ramelteon in the treatment of primary insomnia: 3 in adults and 2 in geriatric patients. Additionally, 2 studies in abstract form that evaluated the long-term effects of ramelteon were included. Data Synthesis: Ramelteon is the first selective melatonin receptor agonist approved by the Food and Drug Administration. It has no affinity for the γ-aminobutyric acid receptor complex or for receptors that bind acetylcholine, cytokines, dopamine, norepinephrine, neuropeptides, opiates, and serotonin. In the only published Phase 3 trial in adults, investigators found that latency to persistent sleep decreased with ramelteon to 31.5 ± 2.91 minutes with 8 mg and 29.5 ± 2.96 minutes with 16 mg compared with 42.5 ± 2.97 minutes with placebo (p = 0.007 and p = 0.002, respectively). Total sleep time was not significantly different from that with placebo. Safety data from short-term studies showed advantages of ramelteon over other sleep agents including no potential for abuse, no rebound insomnia, and lack of effect on motor and cognitive function. The adverse effects seen most frequently in ramelteon clinical trials were headache, somnolence, fatigue, nausea, dizziness, and insomnia. The overall incidence was similar to that of placebo. Conclusions: Ramelteon offers a novel mechanism of action for the treatment of insomnia. Studies support its short- and long-term use in adults and elderly adults for the treatment of primary insomnia characterized by difficulty with sleep initiation. Efficacy studies comparing ramelteon with other sleep agents are needed to further solidify the role of ramelteon in the treatment of insomnia.
Odour monitoring of small wastewater treatment plant located in sensitive environment
Authors: Zarra T. , Naddeo V. , Belgiorno V. , Reiser M. , Kranert M. 
Published: July 2008

Small wastewater treatment plants are often localized nearby tourist areas. Odour emissions are a major environmental issue in these plants and are considered to be the main cause of disturbance noticed by the exposed population. Odour measurement is carried out using analytical or sensorial methods. Sensorial analysis, being assigned to the “human sensor”, is the cause of a considerable uncertainty.
In this study, a novel procedure based on highly innovative analytical tool was used to identify and characterise the odour sources and the volatile substances that cause annoyance in a SWWTP located in a sensitive area, with the aim to remove the subjective component in the measure of the odours and define the induced impact. At the same time key odour compounds are detected, and the relationship between their concentration and the performances of the plant are investigated.
The sources and the main chemical substances responsible for the olfactory annoyances were identified. Results highlight the applicability of the highly innovative tool in odour emission monitoring. Around 39 different substances were detected, with almost half being smell relevant components as well as responsible. Dimethyl disulphide was identified as key compound connected to the efficiency of the process.
“We Only Own the Hours”: Discontinuity of Care in the British Columbia Home Support System
Authors: Sharman Zena , McLaren Arlene Tigar , Cohen Marcy , Ostry Aleck 
Published: July 2008

RÉSUMÉLe présent article utilise le concept de continuité des soins pour examiner les effets de la structuration du système de santé sur les travailleurs et le personnel du programme de soutien à domicile de la Colombie-Britannique (C.-B.). Ce programme dessert principalement les personnes âgée fragiles vivant dans la pauvreté, et il permet d'obtenir de l'aide pour des tâches comme le bain, l'habillement, et la toilette, et offre aussi un soutien social et relationnel spécial aux clients isolés. En présentant des données qualitatives tirées de groupes de discussion et d'entrevues avec des personnes assignées au soutien à domicile et des clients de la région métropolitaine de Vancouver, nous indiquons comment la précarisation et l'intensification du travail, dans un contexte d'un niveau accru d'acuité et de complexité des besoins des clients, ont réduit la continuité et la qualité des soins. Le présent article parle de la façon dont la restructuration du secteur du soutien à domicile en Colombie-Britannique a réduit le nombre total de personnes bénéficiant de soins dans le cadre du système, perturbé la continuité des soins, et compromis la qualité.
Oral Minoxidil vs Topical Minoxidil for Male Androgenetic Alopecia
Authors: Penha Mariana Alvares , Miot Hélio Amante , Kasprzak Michal , Müller Ramos Paulo 
Published: April 2024

ImportanceThere has been increased interest in low-dose oral minoxidil for androgenetic alopecia (AGA) treatment. However, the efficacy of oral minoxidil for male AGA is yet to be evaluated in comparative therapeutic trials.ObjectiveTo compare the efficacy, safety, and tolerability of daily oral minoxidil, 5 mg, vs twice-daily topical minoxidil, 5%, for 24 weeks in the treatment of male AGA.Design, Setting, and ParticipantsThis double-blind, placebo-controlled randomized clinical trial was conducted at a single specialized clinic in Brazil. Eligible men with AGA aged 18 to 55 years classified using the Norwood-Hamilton scale as 3V, 4V, or 5V were included and randomized. Data were collected from January to December 2021, and data were analyzed from September 2022 to February 2023.InterventionsParticipants were randomized 1:1 into 2 groups: oral minoxidil, 5 mg, daily and topical placebo solution; or 1 mL of topical minoxidil, 5%, twice daily and oral placebo for 24 weeks.Main Outcomes and MeasuresThe primary outcome was change in terminal hair density on the frontal and vertex regions of the scalp. The secondary outcomes were change in total hair density and photographic evaluation.ResultsAmong 90 enrolled participants, 68 completed the study; of these, the mean (SD) age was 36.6 (7.8) years. A total of 33 participants were enrolled in the oral minoxidil group and 35 in the topical treatment group. Both groups were homogenous in terms of demographic data and AGA severity. For the frontal area, the mean change from baseline to week 24 between groups was 3.1 hairs per cm2 (95% CI, −18.2 to 21.5; P = .27) for terminal hair density and 2.6 hairs per cm2 (95% CI, −10.3 to 15.8; P = .32) for total hair density. For the vertex area, the mean change from baseline to week 24 was 23.4 hairs per cm2 (95% CI, −0.3 to 43.0; P = .09) for terminal density and 5.5 hairs per cm2 (95% CI, −12.5 to 23.5; P = .32) for total hair density. According to the photographic analysis, oral minoxidil was superior to topical minoxidil on the vertex (24%; 95% CI, 0 to 48; P = .04) but not on the frontal scalp (12%; 95% CI, −12 to 36; P = .24). The most common adverse effects in the oral minoxidil group were hypertrichosis (22 of 45 [49%]) and headache (6 of 45 [14%]).Conclusions and RelevanceIn this study, oral minoxidil, 5 mg, once per day for 24 weeks did not demonstrate superiority over topical minoxidil, 5%, twice per day in men with AGA.Trial RegistrationBrazilian Registry of Clinical Trials Identifier: RBR-252w9r
Acute Adverse Effects of Therapeutic Doses of Psilocybin
Authors: Yerubandi Akhila , Thomas Jennifer E. , Bhuiya N. M. Mahmudul Alam , Harrington Catherine , Villa Zapata Lorenzo , Caballero Joshua 
Published: April 2024

ImportancePsilocybin has been studied in the treatment of depression and anxiety disorders. Clinical studies have mainly focused on efficacy, with systematic reviews showing favorable efficacy; however, none have primarily focused on psilocybin safety.ObjectiveTo evaluate the acute adverse effects of psilocybin at therapeutic doses in the treatment of depression and anxiety.Data SourcesMEDLINE via PubMed, Web of Science, and ClinicalTrials.gov were searched for publications available between 1966 and November 30, 2023.Study SelectionRandomized, double-blind clinical trials that reported adverse effects of psilocybin in patients treated for depression and anxiety were screened.Data Extraction and SynthesisData were independently extracted by 2 authors and verified by 2 additional authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. The inverse variance method with the Hartung-Knapp adjustment for the random-effects model was used, with a continuity correction of 0.5 for studies with 0 cell frequencies. Sensitivity analysis was conducted by sequentially removing 1 study at a time to assess the robustness of the results.Main Outcomes and MeasuresThe primary outcome was considered as the adverse effects of psilocybin at high and moderate (ie, therapeutic) dose regimens and compared with placebo, low-dose psilocybin, or other comparator in the treatment of depression and/or anxiety.ResultsSix studies met the inclusion criteria with a total sample of 528 participants (approximately 51% female; median age 39.8 years; IQR, 39.8-41.2). Seven adverse effects were reported in multiple studies and included in the analysis. Among these, headache (relative risk [RR], 1.99; 95% CI 1.06-3.74), nausea (RR, 8.85; 95% CI, 5.68-13.79), anxiety (RR, 2.27; 95% CI, 1.11-4.64), dizziness (RR, 5.81; 95% CI, 1.02-33.03), and elevated blood pressure (RR, 2.29; 95% CI, 1.15- 4.53) were statistically significant. Psilocybin use was not associated with risk of paranoia and transient thought disorder.Conclusions and RelevanceIn this meta-analysis, the acute adverse effect profile of therapeutic single-dose psilocybin appeared to be tolerable and resolved within 48 hours. However, future studies need to more actively evaluate the appropriate management of adverse effects.