Identifying human enteric parasitic infections in Greece, with focus on Giardia and Cryptosporidium.

A study was conducted in two different areas in Greece to investigate the presence of intestinal human parasitic infections (targeting healthy and individuals with diarrhoea). In total, 876 stool samples were collected from 822 adults and 54 children. Both sedimentation (acid/ether) and concentration/flotation techniques were performed in all samples to detect intestinal parasites. Additionally, a quantitative direct immunofluorescence assay was used specifically for the detection of Giardia and Cryptosporidium. PCR followed by sequencing was applied to genotype Giardia and Cryptosporidium positive samples. Thirty-five (4%) of the individuals examined harboured at least one species of intestinal parasite, the majority of which were protozoa (3.8%). The species found were Blastocystis hominis (1.8%), Giardia duodenalis (1.3%), Cryptosporidium spp. (0.6%), Entamoeba coli (0.2%) and E. histolytica/E. dispar (0.1%). Two persons were positive for Enterobius vermicularis. Genotyping results revealed the presence of G. duodenalis sub-assemblage AII, whereas sequencing was not successful for Cryptosporidium positive samples. A novel multi-locus genotype of G. duodenalis was identified, which has not been described in humans or animals previously. Overall, in the studied population, infection rates with intestinal parasites were low and similar to previous published data. As infection levels were low, no associations could be made between infection status and clinical relevance, risk factors or indication of potential sources of infection, apart from the fact that infections with Giardia were positively correlated to diarrhoea. Based on the parasite species and genotypes detected, there was no indication that animals were an important source of infection. Thus, it is suggested that Giardia infections were more likely to be acquired via human-to-human transmission, either involving indirect pathways such as contaminated food or water, or via direct contact.

Nanoscale structural mapping as a measure of maturation in the murine frontal cortex.

Atomic force microscopy (AFM) is emerging as an innovative tool to phenotype the brain. This study demonstrates the utility of AFM to determine nanomechanical and nanostructural features of the murine dorsolateral frontal cortex from weaning to adulthood. We found an increase in tissue stiffness of the primary somatosensory cortex with age, along with an increased cortical mechanical heterogeneity. To characterize the features potentially responsible for this heterogeneity, we applied AFM scan mode to directly image the topography of thin sections of the primary somatosensory cortical layers II/III, IV and V/VI. Topographical mapping of the cortical layers at successive ages showed progressive smoothing of the surface. Topographical images were also compared with histochemically derived morphological information, which demonstrated the deposition of perineuronal nets, important extracellular components and markers of maturity. Our work demonstrates that high-resolution AFM images can be used to determine the nanostructural properties of cortical maturation, well beyond embryonic and postnatal development. Furthermore, it may offer a new method for brain phenotyping and screening to uncover topographical changes in early stages of neurodegenerative diseases.

Persistent neuropsychiatric impairment in HCV patients despite clearance of the virus?!

One of the most disabling symptoms of hepatitis C virus (HCV) infection is chronic fatigue. While this is accepted for HCV polymerase chain reaction (PCR)-positive patients, a relationship between HCV infection and chronic fatigue is questioned after successful virus eradication. As fatigue is a subjective criterion, we aimed to evaluate in addition mood alterations and cognitive function in HCV-exposed patients with only mild liver disease and to assess a) possible interrelationships between these factors and health-related quality of life and b) the impact of viremia and former interferon treatment. One hundred and fifty-nine anti-HCV-positive individuals without advanced liver disease answered health-related quality of life (HRQoL), fatigue and depression questionnaires and underwent a battery of attention and memory tests. Accompanying diseases which could distort the results of the study such as HIV co-infection or drug addiction were exclusion criteria. The patients were subdivided into four groups according to their viremia status and interferon treatment history. Patients' data were evaluated with respect to norms given in the respective test manuals and in addition compared to those of 33 age-matched healthy controls. Eighty-five per cent of the patients had chronic fatigue, 50-60% mild depression or anxiety, 45% memory deficits and 30% attention deficits, irrespective of their HCV viremia status or treatment history. HRQoL correlated negatively with chronic fatigue (P<.001), while cognitive deficits-especially memory function-were independent from fatigue and depression. HCV infection may cause long-standing cerebral dysfunction that significantly impairs HRQoL and may even persist after clearance of the virus.

Symptomatic cervical perineural (Tarlov) cyst: a case report.

BACKGROUND: Perineural (Tarlov) cysts are benign, usually asymptomatic, cerebrospinal fluid filled cysts of the spine, most often found in the sacral region. DESCRIPTION OF CASE: We report a Tarlov cyst, located in the cervical spine, in a 44-year-old woman who presented with a 3-week history of radicular symptoms of the right C6 root. The perineural cyst was identified at the C5-C6 level following magnetic resonance imaging of the cervical spine. A conservative approach was chosen, with the use of a soft cervical collar for two weeks, a 15-day-course of oral non-steroidal anti-inflammatory medication and instructions concerning limitation of her activities. The outcome of this approach was 90% improvement of her symptoms 24 months after her diagnosis. CONCLUSION: This is the first report of a cervical Tarlov cyst treated conservatively without the use of oral or injected steroids. The perineural cyst should be included in the differential diagnosis of patients presenting with radicular symptoms. Hippokratia 2015, 19 (1): 76-77.

Celiomesenteric trunk demonstrated by multi-detector computed tomography angiography: two cases of a rare vascular variation.

We present two cases of patients with celiomesenteric trunk in whom the celiac trunk and the superior mesenteric artery arise off a common vessel from the ventral part of the aorta, which was demonstrated by multi-detector (16 slices) computed tomography angiography (MDCTA) and confirmed by digital subtraction angiography (DSA). This is a very rare congenital vascular anomaly and its imaging demonstration is of great importance in several interventional procedures. These cases demonstrate the capability of MDCTA in the evaluation of abdominal aorta and its branches and shows that this method might replace diagnostic DSA.

Acute calcific tendinitis of the longus colli muscle: case report and review of the literature.

PURPOSE: Acute calcific tendinitis of the longus colli muscle (or retropharyngeal tendinitis) is an aseptic inflammatory process characterized by acute posterior neck pain, neck stiffness and dysphagia or odynophagia. Awareness of its existence is crucial in the differential diagnosis, because many other conditions, such as retropharyngeal abscess, meningitis or disc herniation, show similar clinical features. We present a case exhibiting an uncommon symptom (torticollis) and a brief literature review to emphasize the risk of misdiagnosis. METHODS: A 36-year-old woman presented with neck stiffness and torticollis accompanied by dysphagia and prevertebral space sensitivity on the second day. RESULTS: The diagnosis was established by computed tomography (CT), the gold standard for identifying the presence of prevertebral oedema and calcific deposition associated with retropharyngeal tendinitis. Treatment with NSAIDs and low doses of corticosteroids relieved the symptoms within 48 h. CONCLUSIONS: Retropharyngeal tendinitis is an underreported entity in the literature and orthopaedists should become aware of its existence. Misdiagnosis of this important mimicker may lead to unnecessary antibiotics administration and interventions in the retropharyngeal space.

Array-based pharmacogenomics of molecular-targeted therapies in oncology.

The advent of microarrays over the past decade has transformed the way genome-wide studies are designed and conducted, leading to an unprecedented speed of acquisition and amount of new knowledge. Microarray data have led to the identification of molecular subclasses of solid tumors characterized by distinct oncogenic pathways, as well as the development of multigene prognostic or predictive models equivalent or superior to those of established clinical parameters. In the field of molecular-targeted therapy for cancer, in particular, the application of array-based methodologies has enabled the identification of molecular targets with 'key' roles in neoplastic transformation or tumor progression and the subsequent development of targeted agents, which are most likely to be active in the specific molecular setting. Herein, we present a summary of the main applications of whole-genome expression microarrays in the field of molecular-targeted therapies for solid tumors and we discuss their potential in the clinical setting. An emphasis is given on deciphering the molecular mechanisms of drug action, identifying novel therapeutic targets and suitable agents to target them with, and discovering molecular markers/signatures that predict response to therapy or optimal drug dose for each patient.

Thrombospondin-1 expression in breast cancer: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components.

Thrombospondin (TSP-1) is a 450-kd adhesive glycoprotein that was initially discovered in platelets and subsequently in a variety of cell types. Several reports suggest that TSP-1 possesses tumour suppressor function, through its ability to inhibit tumour neovascularization. In this study we investigated tissue sections from 124 breast carcinomas for the immuno-histochemical expression of TSP-1 protein and its relationship to several clinicopathological parameters. The possible relationship to hormone receptors content, p53 protein, proliferation associated indices, angiogenesis, VEGF expression and extracellular matrix components (tenascin, fibronectin, laminin, collagen type IV and syndecan-1) was also estimated. TSP-1 was detected in the perivascular tissue, at the epithelial-stromal junction, in the stroma and in the tumour cells. High tumour cell TSP-1 expression was observed in 9.7%, moderate in 17.7%, mild in 10.5%, while 62.1% of the cases were negative for TSP-1 expression. The survival analysis showed an increased risk of recurrence associated with low TSP-1 tumour cell expression. High stromal TSP-1 expression was observed in 3.2% of the cases, moderate in 3.3%, mild in 27.4%, while 63.6% of the cases showed absence of TSP-1 expression. This expression was higher in invasive lobular type of breast cancer and inversely correlated with the lymph node involvement and the estrogen receptor content. Stromal TSP-1 expression was also positively correlated with extracellular matrix components expression, tenascin, fibronectin, collagen type IV, laminin, and syndecan-1. The relationship of TSP-1 expression with tumor angiogenesis, growth fraction and p53 protein expression was not significant. Our data suggest that TSP-1 expression seems to be associated with favorable biological behavior and may have clinical value in terms of predicting the risk of recurrence. In addition, TSP-1 might not be a direct anti-angiogenic factor, although it seems to be implicated in the remodeling of breast cancer tissue through interaction with other extracellular matrix components.

Evidence for neuroinflammation and neuroprotection in HCV infection-associated encephalopathy.

OBJECTIVE: Fatigue, mood disturbances and cognitive dysfunction are frequent in patients infected with hepatitis C virus (HCV) who have mild liver disease. The reason is still unclear. The present study aims to gain more insight into the pathomechanism by combining an extensive neuropsychological examination with magnetic resonance spectroscopy in four different brain regions in a patient group covering the whole spectrum of neuropsychiatric findings in patients afflicted with HCV who have only mild liver disease. METHODS: 53 HCV-positive patients with only mild liver disease and differing degrees of neuropsychiatric symptoms were studied with single-voxel MRS of the parietal white matter, occipital grey matter, basal ganglia and pons. Brain metabolite concentrations were quantitatively analysed by using LCmodel. MRS data were compared to those of 23 healthy controls adjusted for age, and analysed for relationships with the extent of neuropsychiatric symptoms. RESULTS: Choline (p=0.02), creatine (p=0.047) and N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (NN, p=0.02) concentrations in the basal ganglia and choline concentrations in the white matter (p=0.045) were significantly higher in the patients than in controls. Interestingly, the difference was most evident for the patients with low fatigue scores (eg, white matter: choline: p=0.001, creatine: p=0.003, NN: p=0.031). Myo-inositol differed significantly between groups in the white (p=0.001) and grey matter (p=0.003). Fatigue correlated negatively with white matter NN, choline and creatine and myo-inositol levels in white and grey matter and basal ganglia (p<0.01). CONCLUSION: As the increase of choline, creatine and myo-inositol are usually interpreted to indicate glial activation and macrophage infiltration in chronic inflammation and slow virus infections of the brain the present data endorse the hypothesis, that HCV infection may induce neuroinflammation and brain dysfunction. The concomitant increase of NN and the negative correlation to the extent of fatigue suggest a cerebral compensatory process after HCV infection.

Transgenic mice as a model of pre-clinical Alzheimer's disease.

At diagnosis, Alzheimer's disease (AD) brains are extensively burdened with plaques and tangles and display a degree of synaptic failure most likely beyond therapeutic treatment. It is therefore crucial to identify early pathological events in the progression of the disease. While it is not currently feasible to identify and study early, pre-clinical stages of AD, transgenic (Tg) models offer a valuable tool in this regard. Here we investigated cognitive, structural and biochemical CNS alterations occurring in our newly developed McGill-Thyl-APP Tg mice (over-expressing the human amyloid precursor protein with the Swedish and Indiana mutations) prior to extracellular plaque deposition. Pre-plaque, 3-month old Tg mice already displayed cognitive deficits concomitant with reorganization of cortical cholinergic pre-synaptic terminals. Conformational specific antibodies revealed the early appearance of intracellular amyloid ß (Aß)-oligomers and fibrillar oligomers in pyramidal neurons of cerebral cortex and hippocampus. At the same age, the cortical levels of insulin degrading enzyme -a well established Aß-peptidase, were found to be significantly down-regulated. Our results suggest that, in the McGill-Thy1-APP Tg model, functional, structural and biochemical alterations are already present in the CNS at early, pre-plaque stages of the pathology. Accumulation of intraneuronal neurotoxic Aß-oligomers (possibly caused by a failure in the clearance machinery) is likely to be the culprit of such early, pre-plaque pathology. Similar neuronal alterations might occur prior to clinical diagnosis in AD, during a yet undefined 'latent' stage. A better understanding of such pre-clinical AD might yield novel therapeutic targets and or diagnostic tools.

Arterial spasm mimicking superficial femoral artery trauma. Case report.

The existence of traumatic arterial spasm in large arteries is questionable in current literature. We report a case of a 19-year old man with comminuted unstable femur fracture who presented with an ischemic foot. Localized arterial spasm was revealed in the middle portion of the superficial femoral artery triggered by the external pressure of a spicular bone segment was revealed by arteriography. Complete resolution of ischemic symptoms followed fracture reduction. Traumatic arterial spasm although rare does exist.

Metazoan origins of DNA replication: regulation through dynamic chromatin structure.

DNA replication in eukaryotes is initiated at multiple replication origins distributed over the entire genome, which are normally activated once per cell cycle. Due to the complexity of the metazoan genome, the study of metazoan replication origins and their activity profiles has been less advanced than in simpler genome systems. DNA replication in eukaryotes involves many protein-protein and protein-DNA interactions, occurring in multiple stages. As in prokaryotes, control over the timing and frequency of initiation is exerted at the initiation site. A prerequisite for understanding the regulatory mechanisms of eukaryotic DNA replication is the identification and characterization of the cis-acting sequences that serve as replication origins and the trans-acting factors (proteins) that interact with them. Furthermore, in order to understand how DNA replication may become deregulated in malignant cells, the distinguishing features between normal and malignant origins of DNA replication as well as the proteins that interact with them must be determined. Based on advances that were made using simple genome model systems, several proteins involved in DNA replication have been identified. This review summarizes the current findings about metazoan origins of DNA replication and their interacting proteins as well as the role of chromatin structure in their regulation. Furthermore, progress in origin identification and isolation procedures as well as potential mechanisms to inhibit their activation in cancer development and progression are discussed.

On the interface magnetism of thin oxidized Co films: orbital and spin moments.

An x-ray magnetic circular dichroism study of a polycrystalline Co/CoO bilayer is presented. Using both the chemical specificity and surface sensitivity in the core level techniques, we find that uncompensated Co(2+) spin moments participate in the remanent ferromagnetic response of the bilayer that has oxygen nearest neighbors. These are likely located at the Co/CoO interface. As intermixing of magnetic species is not present in Co/CoO, it is concluded that the observed interface moments are due to interface roughness. Given their direction, these moments appear to not directly correlate to the exchange bias in these bilayers.

Infected ruptured popliteal artery aneurysm by Listeria monocytogenes. A case report and review of the literatures.

We describe a case of a voluminous infected aneurysm of the popliteal artery, with Listeria monocytogenes (LM) associated with rupture, in a 72-year old man. After radical resection of the aneurysm a reconstruction was not necessary, because of the sufficient blood supply, due to the pre-existent good development of collateral circulation. The patient was discharged on the 12th postoperative day with primary healing of the wound and viable leg. Adequate antibiotic treatment was continued for 4 weeks. In the following 18 months the serial clinical examinations, laboratory tests and ultrasound scans have shown no evidence of reinfection.

Influence of ligand states on the relationship between orbital moment and magnetocrystalline anisotropy.

The spin and orbital moments of Au/Co/Au trilayers grown on a W(110) single crystal substrate have been investigated by means of x-ray magnetic circular dichroism. Our findings suggest that the orbital moment of Co does not obtain a maximum value along the easy axis, in contrast with previous experience. This is attributed to the large spin-orbit interaction within the Au caps. Both second order perturbation theory and first principles calculations show how the magnetocrystalline anisotropy (MCA) is dramatically influenced by this effect, and how this leads to the fact that the orbital moment anisotropy is not proportional to the MCA.

High intracellular concentrations of amyloid-beta block nuclear translocation of phosphorylated CREB.

The beta-amyloid peptide (Abeta) is considered responsible for the pathogenesis of Alzheimer's disease. Despite the magnitude of reports describing a neurotoxic role of extracellular Abeta, the role for intracellular Abeta (iAbeta) has not been elucidated. We previously demonstrated that in rat pheochromocytoma cells expression of moderate levels of Abeta results in the up-regulation of phospho-extracellular signal-regulated kinases (ERK1)/2 along with an elevation of cyclic AMP-response element (CRE)-regulated gene expression; however, the effect of high intracellular levels of Abeta were not examined. Towards this goal we generated constructs that endogenously produce different expression levels of iAbeta in a human cell line. We show a bimodal response to Abeta in a neural human cell line. A moderate increase of endogenous Abeta up-regulates certain cyclic AMP-response element-binding protein (CREB) responsive genes such as presenilin 1, presenilin 2, brain-derived neurotrophic factor, and mRNA and protein levels by CREB activation and Synapsin 1 nuclear translocation. On the other hand, high-loads of iAbeta resulted in sustained hyper-phosphorylation of CREB that did not translocate to the nucleus and did not stimulate activation of CRE-regulated gene expression. Our study suggests that variations in levels of iAbeta could influence signaling mechanisms that lead to phosphorylation of CREB, its nuclear translocation and CRE-regulated genes involved in production of Abeta and synaptic plasticity in opposite directions.

Abdominal aortic aneurysm in association with horseshoe kidney.

We report the preoperative diagnosis and surgical treatment of an abdominal aortic aneurysm (AAA) in association with a horseshoe kidney (HSK) in a 70-year-old man. Through a median laparotomy a vascular tube graft was successfully used for repair the AAA. The extensive parenchymal isthmus overlying the aneurysm remained intact.

Penetrating craniocerebral injury caused by a pneumatic nail gun: an unsuccessful attempt of suicide.

Nail guns are powerful tools commonly used in the building industry. As a result of their improper use, many accidents of bodily injury, including death, have already been reported over the last 50 years; their use in suicide attempts, however, is rare. In this paper, an unusual case of unsuccessful suicidal craniocerebral penetrating injury committed with a pneumatic nail gun by a 23-year-old man is presented. The particular findings that suggest a suicidal attempt are also discussed.

Mutational analysis of the cell cycle inhibitor Kip1/p27 in childhood leukemia.

BACKGROUND: Cyclin-dependent kinases (CDKs) and cyclins, their regulatory subunits, govern cell-cycle progression in eukaryotic cells. Kip1/p27 is the main cyclin-dependent kinase inhibitor, which arrests cell division inhibiting G1-S transition. Kip1/p27 seems to play a critical role in the pathogenesis of several human malignancies and its lower expression has been shown to correlate with a poor prognosis in adult solid tumors. METHODS: Bone marrow blasts from 49 children with leukemia, 37 acute lymphoblastic leukemia (ALL), and 12 acute myeloid leukemia (AML) were studied. Exon 3 of Kip1/p27 was amplified using the polymerase chain reaction technique (PCR). Single strand conformational polymorphism and heterodouplex analysis were performed to detect DNA sequence with altered conformations and were subsequently sequenced to document mutations. RESULTS: Mutations in Kip1/p27 gene were detected in 2 out of 3 T-ALL, 6 out of 12 AML patients, and only 1 out of 34 B lineage ALL cases. Although the patient groups are small, a highly significant relation of the mutation status with the type of leukemia (P = 0.0037) and the risk group according to treatment protocols (P = 0.00021) was estimated. A statistically significant difference in the white blood count was observed (P = 0.019) between the mutated and non-mutated patient groups although no statistically significant association of the mutation status with the hemoglobin and platelets values, karyotype, age, sex, disease progression, and outcome was determined. CONCLUSIONS: Based upon these results, the Kip1/p27 mutations should be considered for further prospective testing as an additional parameter for risk stratification and treatment of childhood leukemia.