In vivo microdialysis with concomitant behavioral analyses were used to examine the effects of amphetamine and cocaine on cholinergic, glutamatergic, dopaminergic and noradrenergic neurotransmission ...and to evaluate the role of these neurotransmitters in stimulant-induced behaviors. Acute and repeated amphetamine administration promoted a dose-dependent increase in striatal extracellular acetylcholine which paralleled the appearance of oral stereotypies. However, these behaviors do not appear to be mediated by a direct effect of amphetamine on cholinergic neurotransmission but via activation of the corticostriatal glutamatergic pathway. Pretreatment with the N-methyl-D-aspartate receptor antagonist, dizocilpine, enhanced the amphetamine-induced caudate dopamine response without affecting the nucleus accumbens dopamine response. The behavioral response to amphetamine was significantly altered by dizocilpine but these changes do not appear to reflect N-methyl-D-aspartate receptor-mediated regulation of dopamine function. Amphetamine and cocaine promoted regionally similar dose- and time-dependent increases in extracellular norepinephrine which generally paralleled the drug-induced behavioral activation. The mechanisms of action of these stimulants at norepinephrine terminals were examined by pretreatment with clonidine, to study the role of impulse flow, or with reserpine, to study the role of vesicular stores of neurotransmitter. The results indicate that the effects of cocaine on norepinephrine are dependent on vesicular stores of norepinephrine and on impulse flow, consistent with cocaine's actions as an uptake blocker. Although the norepinephrine response to amphetamine is also dependent on vesicular stores of the transmitter, the response is only partially dependent on impulse flow. We hypothesize that amphetamine enhances norepinephrine through two consequences of its interaction with the neuronal transport carrier: (1) uptake blockade, which predominates at lower doses, due to the absence of a releasable cytoplasmic pool of norepinephrine, and (2) release, which becomes more prevalent at higher doses, when norepinephrine is displaced by amphetamine from its vesicular storage site. The striatal dopamine response to amphetamine exhibited a somewhat different dependence on vesicular transmitter. Behavioral analyses further confirm a dissociation between the quantitative features of the dopamine and behavioral profiles and suggest that norepinephrine may be involved in modulating some components of the behavioral response.
Background and Objectives
No intraoperative imaging techniques exist for detecting tumor nodules or tumor scar tissues in patients treated with upfront or interval cytoreductive surgery (CS) after ...neoadjuvant chemotherapy (NAC). The aims of this study were to evaluate the role of indocyanine green (ICG) fluorescence imaging (FI) for the detection of peritoneal metastases (PM) and evaluate whether it can be used to detect remnant tumor cells in scar tissue.
Methods
Patients with PM from ovarian cancer admitted for CS were included. ICG, at 0.25 mg per kg of patient weight, was injected intraoperatively after explorative laparotomy before CS.
Results
A total of 108 peritoneal lesions, including 25 scars, were imaged in 20 patients. Seventy‐three were malignant (67.6%) and 35 benign (32.4%). The mean Tumor to Background Ratio (ex vivo) was 1.8 (SD 1.3) in malignant and 1.0 (SD 0.79) in benign nodules (P = 0.007). Of 25 post‐NAC scars, the mean Tumor to Background Ratio (TBR) (in vivo) was 2.06 (SD 1.15) in malignant and 1.21 (SD 0.50) in benign nodules (P = 0.26). The positive predictive value of ICG‐FI to detect tumor cells in scars was 57.1%.
Conclusions
ICG‐FI is accurate to demonstrate PM in ovarian cancer but unable to discriminate between benign and malignant post‐NAC.
Background
The size and focality of the primary tumor in breast cancer (BC) influence therapeutic decision making. The purpose of this study was to evaluate whether preoperative breast magnetic ...resonance imaging (MRI) is helpful for the assessment of tumor size and surgical planning in early BC.
Methods
We performed a retrospective review of a prospectively collected database of 174 patients treated at a single institution for invasive BC who had complete documentation of the tumor size from mammography (MMG), ultrasonography (US), and MRI.
Results
A total of 186 breast tumors were analyzed. Mean tumor size varied by imaging method: 14.7 mm by MMG, 13.8 mm by US, and 17.9 mm by MRI. The concordance between breast imaging techniques (BIT) and final pathology with a cutoff ≤ 2 mm was 34.8% for MRI, 32.1% for US, and 27.2% for MMG. US and MMG underestimated while MRI and MMG overestimated the real tumor size. Concordance was the same in premenopausal women for MRI and US at 35%, while concordance was higher in postmenopausal women for MRI. Correlations between size determined by BIT and histopathological size were best with MRI (0.59), compared to US (0.56) or MMG (0.42). Intrinsic subtypes of BC had different concordances according to imaging method, but no significant associations were found. MRI examination revealed additional lesions in 13.8% of patients, 69% of these lesions were malignant. MRI changed the surgical plan in 15 patients (8.6%), and the rate of mastectomy increased by 6.9%.
Conclusions
MRI estimates BC tumor size more accurately than US or MMG, but a significant overestimation exists. Complementary MRI examination improved the concordance for tumor size between BIT and final pathology in 16.7%. MRI did not alter surgical planning for most patients and allowed more appropriate treatment for 8% of them.
Aim
This systematic review and meta-analysis aimed to assess the diagnostic accuracy and reliability of commonly used caries detection methods for proximal caries diagnostics. Visual examination ...(VE), bitewing radiography (BWR), laser fluorescence (LF), and fibre-optic transillumination (FOTI) were considered in detail.
Material and methods
PRISMA guidelines for the reporting of systematic reviews and meta-analyses were applied. The mnemonic PIRDS (problem, index test, reference test, diagnostic and study type) concept was used to guide the literature search. Next, studies that met the inclusion criteria were stepwise selected and evaluated for their quality with a risk of bias (RoB) assessment tool. Studies with low/moderate bias and sufficient reporting were considered for meta-analysis. The pooled sensitivity (SE), specificity (SP), diagnostic odds ratio (DOR), and area under the ROC curve (AUC) were calculated.
Results
From 129 studies meeting the selection criteria, 31 in vitro studies and five clinical studies were finally included in the meta-analysis. The AUC values for in vitro VE amounted to 0.84 (caries detection) and 0.85 (dentin caries detection). BWR ranged in vitro from 0.55 to 0.82 (caries detection) and 0.81–0.92 (dentin caries detection). LF showed higher AUC values for overall caries detection (0.91) and dentin caries detection (0.83) than did other methods. Clinical data are limited.
Conclusion
The number of diagnostic studies with low/moderate RoB was found to be low and indicates a need for high-quality, well-designed caries diagnostic studies.
Clinical relevance
BWR and LF showed good diagnostic performance on proximal surfaces. However, because of the low number of includable clinical studies, these data should be interpreted with caution.
Many older patients experience constipation as a bothersome symptom with a negative impact on quality of life. During hospitalization, the focus is often on the reason for admission with the risk ...that other health problems are not prioritized. The aim of the study was to describe the prevalence of constipation and use of laxatives among older hospitalized patients and to investigate the associations with demographic factors, risk assessments and prescribed medications.
A descriptive retrospective cross-sectional study design was used. This study enrolled patients aged 65 years or older admitted to a geriatric department. Data from electronic health records regarding constipation, demographics, risk assessments, medical diagnoses, prescribed medications and length of stay were extracted. Constipation was assessed using ICD- 10 diagnosis, documented signs and symptoms of constipation, and prescribed laxatives. Data was analyzed using descriptive and comparative analyses, including logistic regression.
In total, 6% of the patients had an ICD-10 diagnosis of constipation, 65% had signs and symptoms of constipation, and 60% had been prescribed laxatives. Only 5% of the patients had constipation documented according to ICD-10, signs and symptoms, and prescribed laxatives. Signs and symptoms of constipation were associated with prescribed opioids (OR = 2.254) and longer length of stay (OR = 1.063). Being prescribed laxatives was associated with longer length of stay (OR = 1.109), prescribed opioids (OR = 2.154), and older age (OR = 1.030).
The prevalence of constipation varies depending on the methods used to identify the condition. There was a discrepancy between the documentation of constipation in relation to sign and symptoms, ICD-10 diagnosis and prescribed laxatives. The documentation of constipation was not consistent for the three methods of assessment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Most quantitative research methods are based on measuring either the total or the free concentration of an analyte in a sample. However, this is often insufficient for the study of complex biological ...systems. The main objective of this research was to develop new methods for providing more information from samples: the free concentration (C
), the total concentration (C
), and the plasma binding capacity (PBC). Samples were processed using microextraction and ultrafiltration. For each of these techniques, two quantification procedures were used: addition of isotopically labeled standard and repeated analysis of the same sample. The new methods were validated by analyzing clinical samples and samples with known concentrations. Methods based on addition of labeled compound were found to be the fastest, and most reproducible. For analysis of clinical samples, methods based on microextraction were more sensitive and more accurate than those based on ultrafiltration. For analysis of pooled plasma samples, the overall accuracy of all approaches to determine PBC, testosterone C
, and testosterone C
was between 94 and 109%, 87-113%, and 94-122% respectively. The new approach goes beyond a simple concentration measurement, giving more information from clinical samples, with great potential for personalizing drug dosage and therapy to the needs of individual patients.
Cholangiocarcinoma (CCA) presents significant diagnostic challenges, resulting in late patient diagnosis and poor survival rates. Primary sclerosing cholangitis (PSC) patients pose a particularly ...difficult clinical dilemma because they harbor chronic biliary strictures that are difficult to distinguish from CCA. MicroRNAs (miRs) have recently emerged as a valuable class of diagnostic markers; however, thus far, neither extracellular vesicles (EVs) nor miRs within EVs have been investigated in human bile. We aimed to comprehensively characterize human biliary EVs, including their miR content. We have established the presence of extracellular vesicles in human bile. In addition, we have demonstrated that human biliary EVs contain abundant miR species, which are stable and therefore amenable to the development of disease marker panels. Furthermore, we have characterized the protein content, size, numbers, and size distribution of human biliary EVs. Utilizing multivariate organization of combinatorial alterations (MOCA), we defined a novel biliary vesicle miR‐based panel for CCA diagnosis that demonstrated a sensitivity of 67% and specificity of 96%. Importantly, our control group contained 13 PSC patients, 16 with biliary obstruction of varying etiologies (including benign biliary stricture, papillary stenosis, choledocholithiasis, extrinsic compression from pancreatic cysts, and cholangitis), and 3 with bile leak syndromes. Clinically, these types of patients present with a biliary obstructive clinical picture that could be confused with CCA. Conclusion: These findings establish the importance of using extracellular vesicles, rather than whole bile, for developing miR‐based disease markers in bile. Finally, we report on the development of a novel bile‐based CCA diagnostic panel that is stable, reproducible, and has potential clinical utility. (Hepatology 2014;60:896–907)
An increasing number of genes required for mitochondrial biogenesis, dynamics, or function have been found to be mutated in metabolic disorders and neurological diseases such as Leigh Syndrome. In a ...forward genetic screen to identify genes required for neuronal function and survival in Drosophila photoreceptor neurons, we have identified mutations in the mitochondrial methionyl-tRNA synthetase, Aats-met, the homologue of human MARS2. The fly mutants exhibit age-dependent degeneration of photoreceptors, shortened lifespan, and reduced cell proliferation in epithelial tissues. We further observed that these mutants display defects in oxidative phosphorylation, increased Reactive Oxygen Species (ROS), and an upregulated mitochondrial Unfolded Protein Response. With the aid of this knowledge, we identified MARS2 to be mutated in Autosomal Recessive Spastic Ataxia with Leukoencephalopathy (ARSAL) patients. We uncovered complex rearrangements in the MARS2 gene in all ARSAL patients. Analysis of patient cells revealed decreased levels of MARS2 protein and a reduced rate of mitochondrial protein synthesis. Patient cells also exhibited reduced Complex I activity, increased ROS, and a slower cell proliferation rate, similar to Drosophila Aats-met mutants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Native to the Ponto-Caspian region, the benthic round goby (
Neogobius melanostomus
) has invaded several European inland waterbodies as well as the North American Great Lakes and the Baltic Sea. The ...species is capable of reaching very high densities in the invaded ecosystems, with not only evidence for significant food-web effects on the native biota and habitats, but also negative implications to coastal fishers. Although generally considered a coastal species, it has been shown that round goby migrate to deeper areas of the Great Lakes and other inland lakes during the cold season. Such seasonal movements may create new spatio-temporal ecosystem consequences in invaded systems. To seek evidence for seasonal depth distribution in coastal marine habitats, we compiled all available catch data for round goby in the Baltic Sea since its invasion and until 2017. We furthermore related the depths at capture for each season with the ambient thermal environment. The round goby spend autumn and winter at significantly deeper and offshore areas compared to spring and summer months; few fish were captured at depths < 25 m in these colder months. Similarly, in spring and summer, round goby were not captured at depths > 25 m. The thermal conditions at which round goby were caught varied significantly between seasons, being on average 18.3 °C during summer, and dropping to a low 3.8 °C during winter months. Overall, the fish sought the depths within each season with the highest possible temperatures. The spatial distribution of the round goby substantially overlaps with that of its main and preferred prey (mussels) and with that of its competitor for food (flatfish), but only moderately with the coastal predatory fish (perch), indicating thereby very complex trophic interactions associated with this invasion. Further investigations should aim at quantifying the food web consequences and coupling effects between different habitats related to seasonal migrations of the round goby, both in terms of the species as a competitor, predator and prey.
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