Spontaneous resolution of corneal blood staining.
Herein, a case of a 66-year-old man who developed corneal blood staining secondary to hyphaema after trabeculectomy is reported. No significant increase in intraocular pressure was recorded. The corneal staining spontaneously cleared from the periphery and resolved fully over the following 2 years.


Poly- and mononeuronal innervation in a model for the development of neuromuscular connections.
In the normal development of connections between motor neurons and muscle fibres, an initial stage of polyneuronal innervation is followed by withdrawal of connections until each muscle fibre is innervated by a single axon. However, polyneuronal innervation has been found to persist after prolonged nerve conduction block, in spite of the resumption of normal neuromuscular activity. Here we analyse in detail a model proposed for the withdrawal of nerve connections in developing muscle, based on competition between nerve terminals. The model combines competition for a pre-synaptic resource with competition for a post-synaptic resource. Using bifurcation and phase space analysis, we show that polyneuronal innervation, as well as mononeuronal innervation, can be stable. The model accounts for the development of mononeuronal innervation and for persistent polyneuronal innervation after prolonged nerve conduction block, which appears as a consequence of the general competitive interactions operating during normal development.


Transient activation of the UPRER is an essential step in the acquisition of pluripotency during reprogramming.
Somatic cells can be reprogrammed into pluripotent stem cells using the Yamanaka transcription factors. Reprogramming requires both epigenetic landscape reshaping and global remodeling of cell identity, structure, basic metabolic processes, and organelle form and function. We hypothesize that variable regulation of the proteostasis network and its influence upon the protein-folding environment within cells and their organelles is responsible for the low efficiency and stochasticity of reprogramming. We find that the unfolded protein response of the endoplasmic reticulum (UPRER), the mitochondrial UPR, and the heat shock response, which ensure proteome quality during stress, are activated during reprogramming. The UPRER is particularly crucial, and its ectopic, transient activation, genetically or pharmacologically, enhances reprogramming. Last, stochastic activation of the UPRER predicts reprogramming efficiency in naïve cells. Thus, the low efficiency and stochasticity of cellular reprogramming are due partly to the inability to properly initiate the UPRER to remodel the ER and its proteome.


Preoperative detection of cervical lymph node metastases in papillary thyroid cancer: a surgical perspective.
Despite its relatively benign biological behavior, papillary thyroid cancer is frequently associated with cervical lymph node metastases at the time of diagnosis. These metastases have a limited impact on overall survival, but are recognized as a significant risk factor for locoregional recurrence of the disease. This may significantly alter quality of life, and may require further therapeutic interventions which may be associated with increased morbidity. Therefore, preoperative identification of cervical lymph node metastases is of particular importance and allows optimal and effective treatment at the time of initial surgery. Clinical examination remains important but lacks sensitivity. Neck ultrasonography is currently the most useful method to detect cervical lymphadenopathy. Fine-needle aspiration (for cytology and thyroglobulin measurement), usually under ultrasonographic guidance, may confirm the diagnosis of lymph node metastases. Other imaging methods (including computed tomography, magnetic resonance imaging, positron emission tomography) should be used selectively. A compartment-oriented cervical lymph node dissection should be performed at the time of thyroidectomy if preoperative evaluation reveals cervical lymphadenopathy.


Preoperative Prediction of Axillary Lymph Node Metastasis in Breast Cancer Based on Intratumoral and Peritumoral DCE-MRI Radiomics Nomogram.
To investigate the value of preoperative prediction of breast cancer axillary lymph node metastasis based on intratumoral and peritumoral dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) radiomics nomogram. Material and Methods. In this study, a radiomics model was developed based on a training cohort involving 250 patients with breast cancer (BC) who had undergone axillary lymph node (ALN) dissection between June 2019 and January 2021. The intratumoral and peritumoral radiomics features were extracted from the second postcontrast images of DCE-MRI. Based on filtered radiomics features, the radiomics signature was built by using the least absolute shrinkage and selection operator method. The Support Vector Machines (SVM) learning algorithm was used to construct intratumoral, periatumoral, and intratumoral combined periatumoral models for predicting axillary lymph node metastasis (ALNM) in BC. Nomogram performance was determined by its discrimination, calibration, and clinical value. Multivariable logistic regression was adopted to establish a radiomics nomogram. The intratumoral combined peritumoral radiomics signature, which was composed of fifteen ALN status-related features, showed the best predictive performance and was associated with ALNM in both the training and validation cohorts (P < 0.001). The prediction efficiency of the intratumoral combined peritumoral radiomics model was higher than that of the intratumoral radiomics model and the peritumoral radiomics model. The AUCs of the training and verification cohorts were 0.867 and 0.785, respectively. The radiomics nomogram, which incorporated the radiomics signature, MR-reported ALN status, and MR-reported maximum diameter of the lesion, showed good calibration and discrimination in the training (AUC = 0.872) and validation cohorts (AUC = 0.863). The intratumoral combined peritumoral radiomics model derived from DCE-MRI showed great predictive value for ALNM and may help to improve clinical decision-making for BC.


Phenotypic, Antibiotyping, and Molecular Detection of Klebsiella Pneumoniae Isolates from Clinical Specimens in Kirkuk, Iraq.
Klebsiella Pneumoniae is globally responsible for hospital- and community-acquired infections. This study aimed to determine the prevalence of K. pneumoniae and investigate the antibiotic resistance profile among clinical specimens at Azadi Teaching Hospital in Kirkuk, Iraq, and detect the rpoB gene for molecular identification of K. pneumoniae in comparison with phenotypic and biochemical methods. In total, 250 clinical specimens were collected from patients in Azadi Teaching Hospital in Kirkuk, Iraq, between January 2018 and May 2018. The isolates were identified by morphologic and biochemical testing. Kirby-Bauer disk diffusion method was used in the antibiotics susceptibility test. Following that, 19 (7.6%) K. pneumoniae isolates were isolated from 250 clinical specimens (5 [5.61%] and 14 [8.69%] from males and females, respectively), and most of them (n=12; 11.76%) were isolated from the age group of 10-35 years old. The isolates were reported high resistance towards various types of antibiotics, especially penicillins and cephalosporins. In contrast, K. pneumoniae showed very low resistance to imipenem and amikacin (5.26% and 10.52%, respectively). The range of multidrug-resistant K. pneumoniae isolates in this study was estimated at 100%. In gene detection, all isolates in this study showed PCR product with 108 bp by K. pneumonia specific primer (rpoB). Developed antibiotic policies and regular surveillance of antibiotic susceptibility patterns may help to overcome the indiscriminate use of antibiotics that is a major cause of the emergence of drug resistance among pathogens.


Cervical human papillomavirus prevalence and genotype distribution among hybrid capture 2 positive women 15 to 64 years of age in the Gurage zone, rural Ethiopia.
Human papillomavirus (HPV) infection is a prerequisite of cervical cancer, the leading cause of cancer mortality in Ethiopian women today. Data on Ethiopian cervical HPV prevalence and genotype distribution are rare, but essential as pre-vaccine baseline data to monitor changes after initiating HPV vaccination. The objectives of this study were to assess the cervical HPV prevalence, genotype distribution and associated correlates among female hospital outpatients in rural Ethiopia. We examined a consecutive sample of 537 women 15-64 years of age in rural Ethiopia between November and December 2006. Screening for low risk (LR) and high-risk (HR) cervical HPV infection was performed and HR positive samples were genotyped with a GP5+/6 + - and SPF10-primer based system. The age-standardized prevalence of HPV, HPV HR and HPV LR infection was 17.3% (95% CI 14.1-20.5), 15.8% (95% CI 12.7-18.9) and 3.9% (95% CI 2.3-5.6), respectively. Among HC2 HPV HR positive infections (n = 86), the most common genotype was HPV 16 (24.4%), followed by 52 (11.6%), 56 (10.5%) and 31 (10.5%). Non-married relationship and widowhood, increasing number of lifetime sexual partners, human immunodeficiency virus infection and non-traditional housing type, but not age, were significantly associated with HR HPV infection. These results on cervical HPV prevalence and genotype distribution may serve as baseline data in evaluating the impact of future HPV vaccination programmes in rural Ethiopia.


A 1232 bp upstream sequence of glutamine synthetase 1b from Eichhornia crassipes is a root-preferential promoter sequence.
Glutamine synthetase (GS) acts as a key enzyme in plant nitrogen (N) metabolism. It is important to understand the regulation of GS expression in plant. Promoters can initiate the transcription of its downstream gene. Eichhornia crassipes is a most prominent aquatic invasive plant, which has negative effects on environment and economic development. It also can be used in the bioremediation of pollutants present in water and the production of feeding and energy fuel. So identification and characterization of GS promoter in E. crassipes can help to elucidate its regulation mechanism of GS expression and further to control its N metabolism. A 1232 bp genomic fragment upstream of EcGS1b sequence from E. crassipes (EcGS1b-P) has been cloned, analyzed and functionally characterized. TSSP-TCM software and PlantCARE analysis showed a TATA-box core element, a CAAT-box, root specific expression element, light regulation elements including chs-CMA1a, Box I, and Sp1 and other cis-acting elements in the sequence. Three 5'-deletion fragments of EcGS1b upstream sequence with 400 bp, 600 bp and 900 bp length and the 1232 bp fragment were used to drive the expression of β-glucuronidase (GUS) in tobacco. The quantitative test revealed that GUS activity decreased with the decreasing of the promoter length, which indicated that there were no negative regulated elements in the EcGS1-P. The GUS expressions of EcGS1b-P in roots were significantly higher than those in leaves and stems, indicating EcGS1b-P to be a root-preferential promoter. Real-time Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analysis of EcGS1b gene also showed higher expression in the roots of E.crassipes than in stems and leaves. EcGS1b-P is a root-preferential promoter sequence. It can specifically drive the transcription of its downstream gene in root. This study will help to elucidate the regulatory mechanisms of EcGS1b tissue-specific expression and further study its other regulatory mechanisms in order to utilize E.crassipes in remediation of eutrophic water and control its overgrowth from the point of nutrient metabolism.


Allelotype of neuroblastoma.
Although relatively high incidence of loss of heterozygosity (LOH) on chromosomes 1p, 11q, and 14q have been reported in neuroblastoma, it is still unclear whether or not LOH occurs specifically on these chromosome arms in neuroblastoma since only a few chromosomal arms have been examined for LOH in previous studies. Therefore, we screened 81 cases of tumors for LOH on all 22 autosomes and chromosome X using 35 restriction fragment length polymorphism markers and eight microsatellite markers. High incidence of LOH (> 20%) was observed on six chromosome arms; 1p (26%), 2q (30%), 9p (36%), 11q (24%), 14q (22%), and 18q (31%). Frequencies of LOH on other chromosome arms were less than 13%. Patients with 9p LOH in the tumors showed statistically significant association with advanced stage of the disease and poor prognosis (P = 0.037 and P = 0.003, respectively) independently from N-myc amplification, while LOH on other chromosomes did not show association with stage, prognosis, and N-myc amplification. Thus, besides LOH on chromosomes 1p, 11q, and 14q, LOH on chromosomes 2q, 9p, and 18q also occurs relatively frequently in neuroblastoma, indicating the involvement of multiple tumor suppressor genes in the development of neuroblastoma. It is possible that there is a novel tumor suppressor gene on chromosome 9p which is involved in the progression of neuroblastoma.


Low frequency of H-ras activation in naturally occurring hepatocellular tumors of C3H/HeNCr mice.
Previous reports from several laboratories have consistently shown that approximately 30% of spontaneous hepatocellular adenomas and 70-80% of spontaneous hepatocellular carcinomas found in aged B6C3F1 [C57BL/6 (liver tumor resistant) x C3H (liver tumor susceptible)] male mice contain one of three missense point mutations in codon 61 of the H-ras oncogene, CAA-->AAA, CGA or CTA. Irrespective of subline, the C3H mouse, the paternal parent strain of the B6C3F1 hybrid, is more susceptible to spontaneous liver tumorigenesis than the B6C3F1 mouse. However, the role of H-ras in the pathogenesis of hepatocellular tumors in C3H mice is less clear, as widely different frequencies of activation of this gene, but by the same point mutations in codon 61, have been reported by various laboratories. The present study was undertaken to characterize H-ras involvement in hepatocellular tumors of aged C3H/He mice from the NCI-Frederick Cancer Research and Development Center Colony (C3H/HeNCr). Oncogene activation was evaluated in 45 C3H/HeNCr hepatocellular tumors by the NIH 3T3 transfection assays, and point mutations in the H-ras oncogene were detected and characterized in DNA fragments amplified by PCR, using dot blot hybridization analysis with mutation-specific oligonucleotide probes and direct dideoxy sequencing of PCR products. The only transforming gene detected in these tumors by NIH 3T3 transfection was H-ras. Only 17% (1/6) of spontaneous carcinomas and 8% (3/39) of spontaneous adenomas contained transforming H-ras sequences, each with a point mutation in codon 61. In all four cases with H-ras mutations, mutated sequences comprised a minor fraction of total H-ras gene copies in DNA extracted from primary tumors. H-ras mutations thus appear to have arisen relatively late in the pathogenesis of the neoplasms. For comparison, sections of formalin-fixed, paraffin-embedded hepatocellular tumors that occurred in untreated B6C3F1 hybrid mice sired by C3H/HeNCr males were assayed for the same H-ras mutations by PCR and dot blot hybridization. Nine of 13 such tumors (4/6 carcinomas, 5/7 adenomas) were positive. The overall difference in frequency of H-ras codon 61 mutations in hepatocellular tumors in C3H/HeNCr (4/45) versus B6C3F1 (9/13) was highly significant (P = 0.000035, Fisher's exact test). These data indicate that point mutations in H-ras do not generally play a major or an initiating role in spontaneous hepatocarcinogenesis of inbred C3H/HeNCr mice and contrast with the high rate of ras mutations in liver tumors of the B6C3F1 hybrid.


Delivery systems for natural antioxidant compounds: Archaeosomes and archaeosomal hydrogels characterization and release study.
The aim of this study was to use archaeosomes, a novel kind of liposomes made up by archaeal polar lipids, both multilamellars (MLVs) and unilamellars (SUVs), as a topical delivery system for natural antioxidant compounds recovered from olive mill waste. For comparative purpose an analogue formulation of phosphatidylcholine liposomes was prepared. SUVs were smaller than MLVs ones, showing size values smaller than 200nm, which was maintained during the stability study. Transmission electron microscopy showed spherical morphology for conventional liposomes while archaeosomes had more irregular membranes. Vesicle encapsulation efficiency was quite similar in both formulations and was enough to ensure a good antioxidant activity. Stability studies were performed one month after the preparation of formulations, which showed a high stability with no change in the initial characteristics of the suspensions. Furthermore, the possibility of incorporating the liposomal suspensions in different excipients (Carbopol-940(®) and Pluronic-127(®)) for topical administration was studied. In order to evaluate the release behaviour of the different systems prepared, in vitro diffusion studies were carried out using vertical diffusion Franz cells. In both cases the incorporation of the vesicles into the gels lead in a sustained release for 24h. Archaeosome gels released a similar amount of phenolic compounds regardless the excipient used, while in liposomal gels great release differences were found between carbopol and pluronic gel.


Molecular diseases and diseased molecules: ontological and epistemological dimensions.
In 1949, Linus Pauling and collaborators published in Science a paper provocatively titled: 'Sickle cell anemia, a molecular disease'. What was actually meant by 'molecular disease'? We interpret the concept of molecular disease in the frame of the traditional positions about the nature of diseases, the ontological and the physiological positions. We conclude that the physiological does not give an adequate account of what molecular diseases are. The ontological position, when correctly reinterpreted, leads to an understanding of molecular diseases where the macromolecule is seen as a symptom or as a part of a mechanism leading to the symptoms of the disease. We then show that the concept of molecular disease leads to a particular view of therapy, emphasizing eugenics as a way of eliminating disease. On the individual level, this concept leads to an increased power of diagnosis, and especially predictive diagnosis, but has little therapeutic consequence. Lastly, we examine how this concept of disease unifies two contemporary classifications of diseases, one based on the location of the diseases, the other on the cause of the diseases.


Evaluation of a new battery of toxicity tests for boreal forest soils: assessment of the impact of hydrocarbons and salts.
The ability to assess the toxic potential of soil contamination within boreal regions is currently limited to test species representative of arable lands. This study evaluated the use of six boreal plant species (Pinus banksiana, Picea glauca, Picea mariana, Populus tremuloides, Calamagrostis Canadensis, and Solidago canadensis) and four invertebrate species (Dendrodrilus rubidus, Folsomia nivalis, Proisotoma minuta, and Oppia nitens) and compared their performance to a suite of standard agronomic soil test species using site soils impacted by petroleum hydrocarbon (PHC) and salt contamination. To maintain horizon-specific differences, individual soil horizons were collected from impacted sites and relayered within the test vessels. Use of the boreal species was directly applicable to the assessment of the contaminated forest soils and, in the case of the hydrocarbon-impacted soil, demonstrated greater overall sensitivity (25th percentile of estimated species sensitivity distribution [ESSD25] = 5.6% contamination: 10,600 mg/kg fraction 3 [F3; equivalent hydrocarbon range of >C16 to C34] Of/Oh horizon, and 270 mg/kg F3 Ahg horizon) relative to the standard test species (ESSD25 = 23% contamination: 44,000 mg/kg F3 Of/Oh horizon, and 1,100 mg/kg F3 Ahg horizon). For salinity, there was no difference between boreal and standard species with a combined ESSD25 = 2.3%, equating to 0.24 and 0.25 dS/m for the Ah and Ck horizons. The unequal distribution of soil invertebrates within the layered test vessels can confound test results and the interpretation of the toxic potential of a site. The use of test species relevant to boreal eco-zones strengthens the applicability of the data in support of realistic ecological risk assessments applicable to the boreal regions.


Submicron streptavidin patterns for protein assembly.
Micron and submicron-scale features of aldehyde functionality were fabricated in polymer films by photolithography to develop a platform for protein immobilization and assembly at a biologically relevant scale. Films containing the pH-reactive polymer poly(3,3'-diethoxypropyl methacrylate) and a photoacid generator (PAG) were patterned from 500 nm to 40 mum by exposure to 365 nm (i-line) light. Upon PAG activation and hydrolysis of acetals, aldehyde groups formed. After the films were incubated with a biotinylated aldehyde reactive probe, the X-ray photoelectron spectroscopy results were consistent with biotin being attached to the surface. The background was subsequently passivated by flood exposure and incubation with an aminooxy-terminated poly(ethylene glycol), resulting in a 98% reduction in nonspecific protein adsorption. Protein patterning and assembly was demonstrated using streptavidin, biotinylated anthrax toxin receptor-1, and the protective antigen moiety of anthrax toxin and confirmed by fluorescence microscopy and atomic force microscopy (AFM). AFM demonstrated that 500 nm protein features were achieved. Because of the abundance of biotinylated proteins, this methodology provides a platform for protein immobilization and assembly for various applications in biotechnology.


Chemotherapy after portal vein embolization to protect against tumor growth during liver hypertrophy before hepatectomy.
Portal vein embolization improves the safety of liver resection by increasing the size of residual liver, but the embolization may increase tumor growth during the waiting period before definitive hepatectomy. To determine whether the administration of chemotherapy mitigates tumor growth after portal vein embolization (PVE) performed before major hepatectomy for metastatic colorectal cancer. Review of prospectively collected data at Memorial-Sloan Kettering Cancer Center was conducted. The database included patients subjected to PVE before major hepatectomy for metastatic colorectal cancer. Lesions in both the embolized and nonembolized lobes of the liver before and 1 month after PVE were measured and Response Evaluation Criteria in Solid Tumors were applied to assess disease status. Assessment of survival was based on receipt of post-PVE chemotherapy and then stratified by subsequent resectability. Two hundred eight tumors were measured in 64 patients; 53 tumors were in patients undergoing post-PVE chemotherapy. Approximately one-third of the lesions progressed after PVE when no chemotherapy was administered. This did not differ significantly according to whether tumors were ipsilateral or contralateral to the PVE. When chemotherapy was administered, there was a significantly lower rate of progression (18.9%, P = .03). In long-term follow-up, treatment with post-PVE chemotherapy was also independently associated with improved survival (P < .006). Chemotherapy does not retard growth of the liver after PVE and may prevent cancer progression. Thus, the combination of PVE and chemotherapy may enhance both oncologic and operative safety.


Adjusting the neuron to astrocyte ratio with cytostatics in hippocampal cell cultures from postnatal rats: A comparison of cytarabino furanoside (AraC) and 5-fluoro-2'-deoxyuridine (FUdR).
Cell culture studies offer the unique possibility to investigate the influence of pharmacological treatments with quantified dosages applied for defined time durations on survival, morphological maturation, protein expression and function as well as the mutual interaction of various cell types. Cultures obtained from postnatal rat brain contain a substantial number of glial cells that further proliferate with time in culture leading to an overgrowth of neurons with glia, especially astrocytes and microglia. A well-established method to decrease glial proliferation in vitro is to apply low concentrations of cytosine arabinoside (AraC). While AraC primarily effects dividing cells, it has been reported repeatedly that it is also neurotoxic, which is the reason why most protocols limit its application to concentrations of up to 5 μM for a duration of 24 h. Here, we investigated 5-fluoro-2'-deoxyuridine (FUdR) as a possible substitute for AraC. We applied concentrations of both cytostatics ranging from 4 μM to 75 μM and compared cell composition and cell viability in cultures prepared from 0-2- and 3-4-day old rat pups. Using FUdR as proliferation inhibitor, higher ratios of neurons to glia cells were obtained with a maximal neuron to astrocyte ratio of up to 10:1, which could not be obtained using AraC in postnatal cultures. Patch-clamp recordings revealed no difference in the amplitudes of voltage-gated Na+ currents in neurons treated with FUdR compared with untreated control cells suggesting replacement of AraC by FUdR as glia proliferation inhibitor if highly neuron-enriched postnatal cultures are desired.


Discrimination between random and non-random processes in early bacterial colonization on biomaterial surfaces: application of point pattern analysis.
The dynamics of adhesion and growth of bacterial cells on biomaterial surfaces play an important role in the formation of biofilms. The surface properties of biomaterials have a major impact on cell adhesion processes, eg the random/non-cooperative adhesion of bacteria. In the present study, the spatial arrangement of Escherichia coli on different biomaterials is investigated in a time series during the first hours after exposure. The micrographs are analyzed via an image processing routine and the resulting point patterns are evaluated using second order statistics. Two main adhesion mechanisms can be identified: random adhesion and non-random processes. Comparison with an appropriate null-model quantifies the transition between the two processes with statistical significance. The fastest transition to non-random processes was found to occur after adhesion on PTFE for 2-3 h. Additionally, determination of cell and cluster parameters via image processing gives insight into surface influenced differences in bacterial micro-colony formation.


Phosphoramidon blocks the pressor activity of big endothelin[1-39] and lowers blood pressure in spontaneously hypertensive rats.
In porcine aortic endothelial cells, the 21-amino acid peptide endothelin-1 (ET-1) is formed from a 39-amino acid intermediate big endothelin (big ET) by a putative endothelin-converting enzyme (ECE) that cleaves the 39-mer at the Trp21-Val22 bond. Because big ET has less than 1% of the contractile activity of ET-1, inhibition of ECE should effectively block the biological effects of big ET. Big ET injected intravenously into anesthetized rats produces a sustained pressor response that presumably is due to conversion of big ET to ET-1 by ECE. We determined the type of protease activity responsible for this conversion by evaluating the effectiveness of protease inhibitors in blocking the pressor response to big ET in ganglion-blocked anesthetized rats. The serine protease inhibitor leupeptin, the cysteinyl protease inhibitor E-64, and the metalloprotease inhibitors captopril and kelatorphan were ineffective at blocking the pressor response to big ET. However, the metalloprotease inhibitors phosphoramidon and thiorphan both dose-dependently inhibited the pressor response to big ET, although phosphoramidon was substantially more potent than thiorphan. None of the inhibitors blocked the pressor response to ET-1 and none had any effect on blood pressure when administered alone as an i.v. bolus to the ganglion-blocked anesthetized rat. However, phosphoramidon infused intravenously at 20 mg/kg/h for 4 h lowered the mean arterial pressure (MAP) in conscious spontaneously hypertensive rats (SHRs) whereas kelatorphan at the same dose did not. Our results suggest that ECE is a novel metalloprotease and that ECE inhibitors could have therapeutic potential for the treatment of hypertension.


[Sensitivity and significance of nuclear magnetic tomography findings of finger joints in rheumatoid arthritis].
Evaluation of the sensitivity and value of magnetic resonance imaging (MRI) findings and miniarthroscopic investigations (mini-/needle-arthroscopy = MA) of metacarpophalangeal (MCP) joints in patients with rheumatoid arthritis (RA). 30 patients with RA (21 female, 9 male), disease duration 2 months to 22 years and mean disease activity score (DAS) of 3.90 (range: 2.00-7.67) were examined by MRI of the hand (MCP region) and following MA of the MCP-II joints. MRI parameters for arthritis (synovial enhancement, synovial extension, cortical alterations, joint gap width) and corresponding macroscopic items (synovial extension, synovial hyperemia and vascularity, cortical alterations) by MA, scored semiquantitatively for synovitis (graduated from 0-III degree), were correlated. Additionally, normal radiographs of the hands were performed and compared with MRI findings concerning the detection of bony lesions. Evaluation of the 30 MRI and MA examination revealed highly significant correlations (p < 0.0001) for the parameters of synovial extension (MRI/MA), cortical alterations (MRI/MA) and synovial enhancement (MRI) compared to synovial hyperemia and vascularity (MA). We found significant correlations for parameters of activity and chronicity of RA pathology as assessed by MRI and MA. The detection rate of cortical lesions by MRI was two and a half times higher than by X-ray. MRI findings of MCP-II joints compared to those of MCP III-V showed that the MCP-II joint was more strongly involved.


Hydrogen-bridged chelate ring-assisted π-stacking interactions.
A salicylideneaniline (SA) derivative, (6Z)-6-({[2-(hydroxymethyl)phenyl]amino}methylidene)-3,5-dimethoxycyclohexa-2,4-dien-1-one monohydrate, has an increased aromaticity within its hydrogen-bridged chelate ring owing to its NH character. In the reported crystal structure, nonconventional π-stacking interactions, which are referred to as hybrid π-stacking interactions, are observed between a quasiaromatic chelate ring, formed as a result of the resonance-assisted intramolecular hydrogen bond and ordinary aromatic rings. Besides, π-stacking interactions are also seen between two hydrogen-bridged quasiaromatic chelate rings, which are referred to as pure π-stacking interactions. A CSD search has revealed that both kinds of interactions are frequently observed in molecular crystals of SA derivatives in fully or partially NH tautomeric form, and aromaticity levels of certain fragments of SA derivatives have dramatic effects on their stacking arrangements. These interactions are distinguished from the usual π···π interactions by their formation character, i.e. both σ- and π-deficient and σ-deficient character of pure interactions is more pronounced than that of the hybrid ones.


Isometric endurance of the back extensors in school-aged adolescents with and without low back pain.
Studies on back extensor endurance in adolescents are scarce. This study sought to establish reference data and pattern of back extensor endurance in school-aged adolescents with and without low-back pain (LBP) from Nigeria. This study recruited 625 adolescents aged 11 to 19 years from eight randomly selected secondary schools. The modified Biering-Sørensen test of Static Muscular Endurance (BSME) was used to assess isometric endurance of the back extensors. Demographic and anthropometric data were collected. A modified LBP questionnaire was used to assess the presence of LBP. Descriptive and inferential analyses were used to analyze data. Significance was set at 0.05 alpha-level. The mean isometric holding time (IHT) of all the participants was 132.9 $\pm$ 65.6. Males had significantly higher significant (p=0.026) IHT than females. Adolescents without LBP had a higher significant IHT (p=0.042) than those with reported history of previous LBP and those with present LBP (p=0.000) respectively. Using percentile values, poor endurance was defined as IHT that is < 90.0 s and < 67 s for males and females respectively; medium endurance was defined as IHT that ranged between 90 and 193 s and 67 and 170 s for males and females respectively while good endurance was defined as IHT that is > 193 s and > 170 s for males and females respectively. IHT was significantly related to each of body mass index, hip circumference and waist-to-hip ratio (p < 0.05). Isometric back extensors endurance in Nigerian adolescents was comparable to the original Biering-Sørensen mean value. Majority of the participants had medium endurance performance with the back endurance pattern in the ratio 1:2:1. Male had higher isometric back extensors endurance than females. Decreased isometric back extensors endurance was associated with the presence of LBP in adolescents.


Treating medication-resistant panic disorder: predictors and outcome of cognitive-behavior therapy in a Brazilian public hospital.
In Brazil, treatment of panic disorder is most frequently initiated with pharmacotherapy, but only half of the patients can be expected to be panic free after medication. Studies have suggested that individual or group cognitive-behavior therapy (CBT) is an effective treatment strategy for panic patients who have failed to respond to pharmacotherapy. Thirty-two patients diagnosed with panic disorder with agoraphobia having residual symptoms despite being on an adequate dose of medication were treated with 12 weeks of group CBT. The outcome was evaluated for panic frequency and severity, generalized anxiety, and global severity. Comorbid conditions, a childhood history of anxiety, and defense mechanism styles were assessed as potential predictors of treatment response. Twenty-nine patients completed the 12-week protocol. Treatment was associated with significant reductions in symptom severity on all outcome measures (p < 0.001). Patients with depression had a poorer outcome of the treatment (p = 0.01) as did patients using more neurotic (p = 0.002) and immature defenses (p = 0.05). Consistent with previous reports, we found that CBT was effective for our sample of treatment-resistant patients. Among these patients, depression as well as neurotic defense style was associated with a poorer outcome. The use of CBT in Brazil for treatment-resistant and other panic patients is encouraged.


Hepatorenal syndrome: do the vasoconstrictors work?
The development of hepatorenal syndrome (HRS) is related to many changes associated with advanced cirrhosis. Because vasoconstrictors correct systemic and splanchnic hemodynamic abnormalities, they are effective treatments for HRS, although only in approximately 40% of HRS patients. Emerging data show that combination treatment with vasoconstrictors and TIPS may yield better outcomes than either alone. All HRS patients should be assessed for liver transplantation. Reversing HRS before transplantation is associated with better long-term survival. Combined liver– kidney transplantation is indicated for those with irreversible kidney injury. Otherwise, there is some merit in performing a liver transplant first and only considering a kidney transplant later.


The utility of 68Ga-DOTATATE positron-emission tomography/computed tomography in the diagnosis, management, follow-up and prognosis of neuroendocrine tumors.
Neuroendocrine tumors (NETs) are rare neoplasms that emerge mainly from the GI tract, pancreas and respiratory tract. The incidence of NETs has increased more than sixfold in the last decades. NETs typically express somatostatin receptors on their cell surface, which can be targeted by 'cold' somatostatin analogs for therapy or by 'hot' radiolabeled somatostatin analogs for tumor localization and treatment. 68-Gallium-DOTA peptides (DOTATATE, DOTATOC, DOTANOC) positron emission tomography/computed tomography is a highly accurate imaging modality for NETs that has been found to be more sensitive for NET detection than other imaging modalities. In the current review, we will discuss the clinical utility of 68-Gallium-DOTATATE positron emission tomography/computed tomography for the diagnosis and management of patients with NETs.


Interferon-beta specific T cells are associated with the development of neutralizing antibodies in interferon-beta treated multiple sclerosis patients.
Beta-interferons are still among the most commonly used drugs to treat Multiple Sclerosis (MS). The use of beta-interferons is limited by the development of anti-drug antibodies (ADA), which may abrogate the treatment effect of the drug. Although the antibody response has been well studied, little is known about the T cell response to interferon-beta (IFN-β). We investigated T cell responses in four treatment naïve MS patients and twenty-three patients treated with IFN-β who had or had not developed ADA to IFN-β. T cell responses were determined by split-well and primary proliferation assays against different IFN-β protein preparations and a set of overlapping peptides covering the full sequence of IFN-β. T cell responses to IFN-β were observed in all donors. ADA positive patients showed higher T cell responses to IFN-β protein than ADA negative patients and untreated controls. We identified two immunodominant regions; T cell responses to IFN-β1-40 were observed in all patients independent of ADA status, while T cell responses to IFN-β125-159 were stronger in ADA positive than ADA negative patients. IFN-β specific T cell responses were HLA class II restricted and in ADA positive patients skewed towards a Th2 phenotype. In IFN-β treated patients we observed a correlation between IFN-β specific T cell responses, serum ADA titer and loss of biological activity of IFN-β treatment. Our studies demonstrate the occurrence of an antigen specific HLA class II restricted Th2 T cell response associated with the development of ADA in IFN-β treated patients.


Occult popliteal artery stenosis masquerading as atheroemboli in a patient with previous knee replacement.
The purpose of this article is to report the unusual presentation of a 63-year-old patient with Rutherford grade 2, category 5 tissue ischemic changes involving the right foot secondary to an occult popliteal stenosis that was obscured behind a prosthetic knee on diagnostic angiograms. Conventional abdominal angiography with bilateral lower extremity runoff showed no evidence of significant disease and the patient was misdiagnosed with atheroemboli syndrome secondary to ipsilateral common femoral access following recent catheterization. Ultimately, a meticulous physical examination disclosed a bruit in the right popliteal fossa and selective right leg angiography with oblique views confirmed eccentric complex luminal encroachment in the right popliteal artery that was eclipsed by a prosthetic knee on antecedent nonselective angiography. The lesion responded favorably to endovascular treatment with durable clinical improvement. This case illustrates the importance of a meticulous physical examination and noninvasive studies prior to angiography in patients with ischemic tissue changes and emphasizes the importance of oblique views to image any vessel that may be obscured by a metal prosthesis.


Patient -controlled epidural ropivacaine as a post-Cesarean analgesia: a comparison with epidural morphine.
Conventional, intermittent, epidural morphine is widely applied as a post-Cesarean delivery analgesia. We compared the analgesic efficacy, motor weakness, and side effects of administering a patient-controlled epidural analgesia (PCEA) of pure ropivacaine versus the intermittent administration of epidural morphine after Cesarean delivery. This randomized, double-blind study included 120 full-term parturients who underwent elective Cesarean delivery and received either PCEA with pure ropivacaine or an intermittent bolus epidural of 2 mg/10 mL morphine in normal saline twice per day. The efficacy of pain relief, post-Cesarean side effects, motor blockades, time to first ambulation, and global satisfaction scores were evaluated. Pain scores were recorded at the four evaluation times (2, 12, 24, and 48 hours post-Cesarean delivery), and the time to first ambulation did not statistically differ between the two groups. Patients in the ropivacaine group experienced more motor weakness at 2 and 12 hours, fewer side effects, and higher global satisfaction scores than those in the morphine group (p < 0.05). The analgesic efficacy after cesarean delivery was almost equivalent between two groups. PCEA with pure ropivacaine induced significant motor blockade during the first 12 hours, but without delaying the time to first ambulation. Patients in the ropivacaine group reported higher patient satisfaction scores due to the significant reduction of annoying side effects, such as pruritus, nausea, vomiting, and urinary retention.


Speckle fields generated with binary diffusers and synthetic pupils implemented on a spatial light modulator.
Digitally controllable Gaussian speckle fields were experimentally generated by implementing binary diffusers and synthetic pupils on a liquid crystal spatial light modulator. The synthetic pupil comprises a Ronchi phase mask and a proper filtering of its diffraction orders. The binary diffuser is displayed inside an aperture defined onto the Ronchi phase mask. We demonstrated that this implementation replaces the need of using a ground glass and a physical pupil. In this way, the average speckle size, the statistical independence among the generated speckle patterns, and the average intensity distribution can be dynamically controlled.


Complete Genome Sequence of Rathayibacter toxicus Phage NCPPB3778.
The phage NCPPB3778 was isolated from Rathayibacter toxicus strain CS14, and the genomic DNA was sequenced. The genome is similar to siphoviruses, consisting of 44,520 bases including 77 predicted open reading frames. Portions of the genome are annotated as typical phage proteins, but much of the genome sequence is unique from other bacteriophages.


[Progressive multifocal leukoencephalopathy: virological and neuropathological aspects].
Progressive multifocal leukoencephalopathy is a subacute demyelinating disease of the central nervous system due to an opportunistic infection by a polyomavirus, most often JC virus, which predominantly infects oligodendrocytes. Progressive multifocal leukoencephalopathy used to be a rare condition, usually complicating lymphoproliferative diseases. Since the onset of the AIDS epidemic, its incidence has considerably increased and HIV infection has become, by far, the main risk factor for the disease. In AIDS patients, progressive leukoencephalopathy frequently shows atypical clinical and pathological features. The development of malignant glial tumors, within demyelinating regions, in patients with progressive multifocal leukoencephalopathy, has been reported in exceptional cases. The course of progressive multifocal leukoencephalopathy is invariably fatal. The diagnosis can only be made with certainty by histopathological examination of the brain, on cerebral biopsy or at postmortem. However, neuroradiological features may be extremely suggestive in many cases and PCR seems to be a reliable technique for demonstrating viral genome in the CSF. A few antiviral treatments have been proposed, however their efficacy is difficult to assess due to the low prevalence of the disease and the occurrence of rare cases with spontaneously prolonged survival.


The effect of biomass fuel exposure on the prevalence of asthma in adults in India - review of current evidence.
The combustion of biomass fuels is a major source of respiratory disease among individuals in the developing world. Over two million people world-wide rely on biomass fuels to supply their household energy needs with an estimated 1.6 million deaths annually being attributable to biomass smoke exposure. As a developing country, India relies heavily on the use of solid fuels as a source of energy. These materials supply 75% of the country's domestic energy need and are attributed as the cause of over 600 000 deaths annually. Diseases such as chronic bronchitis and acute lower respiratory tract infections are strongly correlated to biomass smoke exposure. While not as strongly correlated, accumulating evidence suggests that asthma prevalence may be related to solid fuel smoke. This review examines the current literature linking biomass smoke exposure to the reporting of asthma symptoms. A PubMed search was performed using key terms biomass, asthma, India and respiratory disease. Preference was given to recent articles that surveyed the adult population within India. The reviewed articles showed an increased odds ratio for reporting a diagnosis of asthma or symptoms consistent with asthma following biomass smoke exposure. While the literature supports a strong association between household air pollution and the development of chronic bronchitis and acute lower respiratory tract infections in India, this review establishes a more firm relationship between reported asthma symptoms and biomass smoke exposure. The exposure to biomass fuel smoke results in respiratory diseases in developing countries. Among these diseases, asthma appears to be a preventable pulmonary pathology that is associated with household air pollution. Measures to reduce exposure may decrease the burden of disease which could help advance social and economic progress in these nations. Further research and out-reach efforts are needed to reduce the total burden of lung diseases, including asthma, across the developing world. This reduction could save millions of dollars annually and lower morbidity and mortality in the affected populations.


Expression of polymorphic HLA-A,B epitopes in human urothelial cell lines.
Malignant human urothelial cell lines propagated in vitro have previously been demonstrated to express low amounts of monomorphic HLA-A,B,C as compared to premalignant urothelial cells. In this study the expression of polymorphic HLA-A,B epitopes in human urothelial cell lines have been investigated in greater detail. The expression of HLA-B locus coded epitopes in malignant TGrIII cells was demonstrated to be low or absent as compared to pre-malignant TGrII or slightly transformed TGrI cells, suggesting a mechanism by which malignant cells could escape from the host immune response. The extreme polymorphism of HLA-A,B,C antigens suggests that HLA typing could be used as a method to identify the origin of cell lines which is essential in the study of the process of malignant transformation in vitro, or when correlating in vitro data with clinical observations of the patient. Two urothelial cell lines classified as slightly transformed (TGrI) and two as pre-malignant (TGrII) could, according to their expression of polymorphic HLA-A,B epitopes, be identified as genuine independent cell lines. One TGrII cell line previously designated Hu1734 shared the same HLA-A,B phenotype as the genuine HCV29 (TGrII) cell line and is therefore suspected to be a subline of the latter. Out of 18 cell lines and sublines classified as TGrIII the fidelity of four (Hu1922 and three sublines of T24) was proved by their HLA-A,B phenotype. Mistaken identity either by contamination or false labelling of the cultures was suspected in samples of six TGrIII cell lines and sublines. In four of these the HLA-A,B type characteristic for the T24 cell line could be demonstrated, but in general HLA typing of TGrIII cell lines as a method to identify the origin of the individual cell lines failed, primarily due to the decreased expression of HLA-A,B,C antigens and the apparent selective loss of HLA-B locus coded antigens.


Kinetic and thermodynamic characterization of telomeric G-quadruplex by nonequilibrium capillary electrophoresis: application to G-quadruplex/duplex competition.
In this paper, nonequilibrium capillary electrophoresis (NECE) was attempted for the first time to investigate a dual equilibrium system, where the intramolecular G-quadruplex folding was in competition with the intermolecular duplex formation. Samples of an equilibrium mixture of human telomeric DNA and its complementary strands were separated in capillaries under nonequilibrium conditions without K (+). Polyethylene oxide was added to the running buffer facilitating the separation of single-stranded DNA, duplex, and G-quadruplex. Thus, the folding/unfolding rate constants of the G-quadruplex and the association/dissociation constants of the duplex could be simultaneously derived from the same experiment. Results indicated that the duplex formation induced minimal influence on the G-quadruplex folding. On the basis of the kinetic characterization of the G-quadruplex at varying temperatures, the thermodynamic parameters of the G-quadruplex could also be determined. Thus, the NECE method provided a new avenue for studying the kinetics and thermodynamics of nucleic acids within dual equilibrium systems with significant advantages of extreme-low sample cost (approximately 10 (-18) mol) and high repeatability.


Food availability affects circadian clock-controlled activity and Zugunruhe in the night migratory male blackheaded bunting (Emberiza melanocephala).
This study investigated the functional linkage between food availability and activity behavior in the Palaearctic Indian night migratory blackheaded bunting (Emberiza melanocephala) subjected to artificial light-dark (LD) cycles. Two experiments were performed on photosensitive birds. In the first one, birds were exposed to short days (LD 10/14; Experiment 1A), long days (LD 13/11; Experiment 1B), or increasing daylengths (8 to 13 h light/d; Experiment 1C) and presented with food either for the whole or a restricted duration of the light period. In Experiments 1A and 1B, illumination of the light and dark periods or of the dark period, alone, was changed to assess the influence of the light environment on direct and circadian responses to food cycles. In the second experiment, birds were exposed to LD 12/12 or LD 8/16 with food availability overlapping with the light (light and food presence in phase) or dark period (light and food presence in antiphase). Also, birds were subjected to constant dim light (LL(dim)) to examine the phase of the activity rhythms under synchronizing influence of the food cycles. Similarly, the presentation of food ad libitum (free food; FF) during an experiment examined the effects of the food-restriction regimes on activity rhythms. A continuous measurement of the activity-rest pattern was done to examine both the circadian and direct effects of the food and LD cycles. Measurement of activity at night enabled assessment of the migratory phenotype, premigratory restlessness, or Zugunruhe. The results show that (i) light masked the food effects if they were present together; (ii) birds had a higher anticipatory activity and food intake during restricted feeding conditions; and (iii) food at night alone reduced both the duration and amount of Zugunruhe as compared to food during the day alone. This suggests that food affects both the daily activity and seasonal Zugunruhe, and food cycles act as a synchronizer of circadian rhythms in the absence of dominant natural environmental synchronizers, such as the light-dark cycle.


The intravenous and oral pharmacokinetics of afoxolaner and milbemycin oxime when used as a combination chewable parasiticide for dogs.
The pharmacokinetics of afoxolaner and milbemycin oxime (A3 and A4 forms) in dogs were evaluated following the oral administration of NexGard Spectra® (Merial), a fixed combination chewable formulation of these two active pharmaceutical ingredients. Absorption of actives was rapid at levels that provide the minimum effective doses of 2.5 mg/kg and 0.5 mg/kg of afoxolaner and milbemycin oxime, respectively. The time to maximum afoxolaner plasma concentrations (tmax ) was 2-4 h. The milbemycin tmax was 1-2 h. The terminal plasma half-life (t1/2 ) and the oral bioavailability were 14 ± 3 days and 88.3% for afoxolaner, 1.6 ± 0.4 days and 80.5% for milbemycin oxime A3 and 3.3 ± 1.4 days and 65.1% for milbemycin oxime A4. The volume of distribution (Vd ) and systemic clearance (Cls) were determined following an IV dose of afoxolaner or milbemycin oxime. The Vd was 2.6 ± 0.6, 2.7 ± 0.4 and 2.6 ± 0.6 L/kg for afoxolaner, milbemycin oxime A3 and milbemycin oxime A4, respectively. The Cls was 5.0 ± 1.2, 75 ± 22 and 41 ± 12 mL/h/kg for afoxolaner, milbemycin oxime A3 and milbemycin oxime A4, respectively. The pharmacokinetic profile for the combination of afoxolaner and milbemycin oxime supports the rapid onset and a sustained efficacy for afoxolaner against ectoparasites and the known endoparasitic activity of milbemycin oxime.


Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53.
Mdm2 has been shown to regulate p53 stability by targeting the p53 protein for proteasomal degradation. We now report that Mdm2 is a ubiquitin protein ligase (E3) for p53 and that its activity is dependent on its RING finger. Furthermore, we show that Mdm2 mediates its own ubiquitination in a RING finger-dependent manner, which requires no eukaryotic proteins other than ubiquitin-activating enzyme (E1) and an ubiquitin-conjugating enzyme (E2). It is apparent, therefore, that Mdm2 manifests an intrinsic capacity to mediate ubiquitination. Mutation of putative zinc coordination residues abrogated this activity, as did chelation of divalent cations. After cation chelation, the full activity could be restored by addition of zinc. We further demonstrate that the degradation of p53 and Mdm2 in cells requires additional potential zinc-coordinating residues beyond those required for the intrinsic activity of Mdm2 in vitro. Replacement of the Mdm2 RING with that of another protein (Praja1) reconstituted ubiquitination and proteasomal degradation of Mdm2. However, this RING was ineffective in ubiquitination and proteasomal targeting of p53, suggesting that there may be specificity at the level of the RING in the recognition of heterologous substrates.


Effect of head impacts and chemical irritation on elite athletes' olfaction.
Limited research exists on athletes' olfaction. As diet is an elementary part of an athlete's lifestyle and training, it is important to know whether the sport discipline itself carries a risk for olfactory impairment. The aim of this study was to evaluate whether elite swimmers (chemical irritation), boxers (head impact) or soccer players (head impact) are at risk for impaired olfaction. Elite-level male swimmers (n = 30), boxers (n = 35) and soccer players (n = 30) aged 18-40 years were recruited from Finnish sport clubs. Floorball players (n = 30) were recruited as a control group. All participants filled in a questionnaire about their training history, nasal and sinonasal diseases, asthma, nasal operations and traumas, smoking and self-evaluation of olfaction and taste function. Sniffin' Sticks odour identification test with 12 different odorants and anterior rhinoscopy were performed on all participants. The mean score from the smelling test did not differ between the sport groups. Sinonasal diseases and bronchial asthma were more common among swimmers than among the other athletes. Rhinitis symptoms were common among all athletes. Boxing, soccer or swimming does not seem to affect sense of smell. The majority of our participating elite athletes had normal olfaction, even if they had had a long history of active sports.Highlights Boxing, soccer or swimming does not seem to affect sense of smell.Rhinitis symptoms were prevalent among all elite athlete groups in our study.Athletes with hyposmia can perceive their own decreased olfaction.Swimmers have more bronchial asthma and sinus diseases than other athlete groups.


Teaching limited compression ultrasound to general practitioners reduces referrals of suspected DVT to a hospital: a retrospective cross-sectional study.
The aim of this study was to retrospectively determine whether teaching limited compression ultrasound (LCUS) to general practitioners (GP) would reduce the number of patients with a suspected lower extremity DVT referred to a hospital for ultrasound (US) examination. According to the current literature, an LCUS protocol is a safe way to diagnose or exclude lower extremity deep venous thrombosis (DVT) and a good option to radiologist-performed whole-leg ultrasound (US), especially in remote health care units where there may be a limited availability of radiological services. Between 2015 and 2016, altogether 13 GPs working in the same primary care unit were trained in LCUS for DVT diagnostics. The number of annual referrals due to a suspected DVT from Saarikka primary care unit to the closest hospital was evaluated before and after training. The incidence of DVT was considered to be constant. Thus, the reduction of referrals was attributed to the fact that these patients were diagnosed and treated in primary health care. Incidence rate ratio of hospital referrals was calculated. As a measure of safety, all patients diagnosed with a pulmonary embolism in the nearest hospital were evaluated to determine if they had undergone LCUS by a GP in primary care. Before training in 2014, there were 60 annual referrals due to a suspected DVT; in 2017, after training, the number was reduced to 16, i.e., a 73.3% decrease. The incidence of referrals decreased from 3.21 to 0.89 per 1000 person-years. (IRR 3.58, 95% CI 2.04-6.66, p < 0.001). No patient with a pulmonary embolism diagnosis had LCUS performed previously, indicating that there were no false negatives, resulting in pulmonary embolism. Teaching LCUS to GPs can safely reduce the number of patients with a suspected DVT referred to a hospital substantially.


Exploration of organic acid chain length on water-soluble silicon quantum dot surfaces.
Surface functionalization of silicon quantum dots influences oxidation of the silicon core while affording control of physical properties and maintaining optical stability. An effective method for surface modification is photochemical hydrosilylation in which the hydride-terminated Si surface is reacted with an unsaturated C-C bond resulting in a covalent Si-C bond at the surface. The physical properties (e.g., reactivity and solvent compatibility) of the nanocrystals are thus dictated by those of the pendant functional group. Water-soluble nanoparticles can be produced by extending polar functional groups, such as carboxylic acids, from the surface. Previous literature reports have shown acrylic acid to be an attractive starting material for creating water-soluble Si nanocrystals. To date, a detailed study of the effects of differing surface groups (i.e., carboxylic acids of varying carbon chain lengths) has not been offered. Here, we investigate the effects of carboxylic acid surface moieties with increasing carbon chain length on various silicon nanocrystal properties. Oxidative and optical stability was improved by increasing the length of the carbon spacer between the silicon surface and the polar carboxylic acid group. As well, increased chain length was found to enhance nanocrystal dispersibility in polar solvents. Of important note, however, the use of acrylic acid as a precursor led to poly(acrylic acid) formation under the reaction conditions studied, leading to anomalous behavior compared to precursors with longer carbon chains.


Thoracic blastomycosis and empyema.
Blastomycosis is endemic in river valley areas of the southeastern and Midwestern United States. Pulmonary manifestations include chronic cough and pleuritic pain. Radiographic appearance of the infection can mimic bronchogenic lung carcinoma. Pleural effusion is rarely associated with this pulmonary infection, and empyema has not been previously reported. We report a case of pulmonary and pleural Blastomyces dermatitidis infection presenting as empyema thoracis. Diagnosis and treatment were attained with video-assisted thoracoscopic (VATS) pleural and lung biopsy and debridement.


Fungicide dissipation and impact on metolachlor aerobic soil degradation and soil microbial dynamics.
Pesticides are typically applied as mixtures and or sequentially to soil and plants during crop production. A common scenario is herbicide application at planting followed by sequential fungicide applications post-emergence. Fungicides depending on their spectrum of activity may alter and impact soil microbial communities. Thus there is a potential to impact soil processes responsible for herbicide degradation. This may change herbicide efficacy and environmental fate characteristics. Our study objective was to determine the effects of 4 peanut fungicides, chlorothalonil (2,4,5,6-tetrachloro-1,3-benzenedicarbonitrile), tebuconazole (alpha-[2-(4-chlorophenyl)ethyl]-alpha-(1,1-dimethylethyl)-1H-1,2,4-triazole-1-ethanol), flutriafol (alpha-(2-fluorophenyl)-alpha-(4-fluorophenyl)-1H-1,2,4-triazole-1-ethanol), and cyproconazole (alpha-(4-chlorophenyl)-alpha-(1-cyclopropylethyl)-1H-1,2,4-triazole-1-ethanol) on the dissipation kinetics of the herbicide, metolachlor (2-chloro-N-(6-ethyl-o-tolyl)-N-[(1RS)-2-methoxy-1-methylethyl]acetamide), and on the soil microbial community. This was done through laboratory incubation of field treated soil. Chlorothalonil significantly reduced metolachlor soil dissipation as compared to the non-treated control or soil treated with the other fungicides. Metolachlor DT(50) was 99 days for chlorothalonil-treated soil and 56, 45, 53, and 46 days for control, tebuconazole, flutriafol, and cyproconazole-treated soils, respectively. Significant reductions in predominant metolachlor metabolites, metolachlor ethane sulfonic acid (MESA) and metolachlor oxanilic acid (MOA), produced by oxidation of glutathione-metolachlor conjugates were also observed in chlorothalonil-treated soil. This suggested that the fungicide impacted soil glutathione-S-transferase (GST) activity. Fungicide DT(50) was 27-80 days but impacts on the soil microbial community as indicated by lipid biomarker analysis were minimal. Overall study results indicated that chlorothalonil has the potential to substantially increase soil persistence (2-fold) of metolachlor and alter fate and transport processes. GST mediated metabolism is common pesticide detoxification process in soil; thus there are implications for the fate of many active ingredients.


Dynamical characterization of the heme NO oxygen binding (HNOX) domain. Insight into soluble guanylate cyclase allosteric transition.
Since the discovery of soluble guanylate cyclase (sGC) as the mammalian receptor for nitric oxide (NO), numerous studies have been performed in order to understand how sGC transduces the NO signal. However, the structural basis of sGC activation is still not completely elucidated. Spectroscopic and kinetic studies showed that the key step in the activation mechanism was the NO-induced breaking of the iron proximal histidine bond in the so-called 6c-NO to 5c-NO transition. The main breakthrough in the understanding of sGC activation mechanism came, however, from the elucidation of crystal structures for two different prokaryotic heme NO oxygen (HNOX) domains, which are homologues to the sGC heme domain. In this work we present computer simulation results of Thermoanaerobacter tencogensis HNOX that complement these structural studies, yielding molecular explanations to several poorly understood properties of these proteins. Specifically, our results explain the differential ligand binding patterns of the HNOX domains according to the nature of proximal and distal residues. We also show that the natural dynamics of these proteins is intimately related with the proposed conformational dependent activation process, which involves mainly the alphaFbeta1 loop and the alphaA-alphaC distal subdomain. The results from the sGC models also support this view and suggest a key role for the alphaFbeta1 loop in the iron proximal histidine bond breaking process and, therefore, in the sGC activation mechanism.


Simultaneous measurement of temperature and strain based on SCF-based MZI cascaded with FBG.
A novel seven-core fiber (SCF)-based sensor capable of simultaneous measurement of temperature and strain was proposed and experimentally demonstrated. The sensor consists of a fiber Bragg grating (FBG) and a SCF-based Mach-Zehnder interferometer (MZI). The MZI is formed by splicing a short section of SCF between two single-mode fibers (SMFs), and in the meantime, two fiber tapers that act as light splitter and coupler are formed at both ends of the SCF by the fusion splicing method. In addition, the FBG with a central wavelength of 1547.98 nm is cascaded at the end of one fiber taper, and thus simultaneous measurement of temperature and strain can be realized. The experiment result shows that the SCF-based MZI is only sensitive to temperature and has the higher temperature sensitivity of 93.11 pm/°C, while the FBG is sensitive to temperature and strain with sensitivities of 11.46 pm/°C and 0.627pm/µε, respectively. The corresponding temperature and strain resolutions of the sensor are 0.21°C and 27.95µε, respectively. The proposed sensor has the advantages of simple fabrication and high repeatability and has potential applications in many fields such as engineering machinery and building structure health monitoring.


Two distinct retinal projections to the hamster suprachiasmatic nucleus.
Electrical stimulation of the intergeniculate leaflet (IGL) region in hamsters can induce expression of Fos-like immunoreactivity (lir) in a restricted portion of the dorsolateral suprachiasmatic nucleus (SCN). The authors investigated whether the mechanisms by which stimulation affects SCN cells involves orthodromic activation of IGL cells projecting to the SCN or antidromic activation of retinal ganglion cells that send bifurcating axonal projections to both the IGL and the SCN. Bilateral optic enucleation strongly reduced induction of Fos-lir in SCN cells in response to electrical stimulation of the IGL region, implicating antidromic activation of retinal ganglion cells as the mechanism. This result implies that a class of retinal ganglion cells that project to the IGL also project selectively to the dorsolateral SCN. Earlier pharmacological studies suggest that this anatomically distinct retinal projection to the SCN is also neurochemically different from that innervating the rest of the nucleus.


Which repetitive transcranial magnetic stimulation modality affects vasomotor reactivity in healthy subjects and how long does it last?
The aim of our study was to evaluate the effects of low and high-frequency repetitive transcranial magnetic stimulation (rTMS) on hypoxia-induced changes in bilateral cerebrovascular reserve up to 24 h in the same individuals. Right-handed ten healthy male individuals participated in the study. All participants had neither drug therapy nor a concomitant disease and none of them had a variation in the circle of Willis, intracranial stenosis, arteriovenous malformation, or aneurysm which may have an impact on transcranial doppler ultrasound (TCD) examination and transcranial magnetic stimulation (TMS) recording. There was a statistically significant difference in the breath-holding index (BHI) between before and after 0, 15, 30 min after 1 Hz repetitive stimulation (p < 0.05). When applying 5 Hz repetitive stimulation there was no difference before and after BHI values (p > 0.05). There were no differences in bilateral, ipsilateral, or contralateral middle cerebral artery (MCA) mean cerebral blood flow velocity (CBFV) after low or high-frequency rTMS application (p > 0.05). The main result of the study was that low-frequency rTMS reduced vasomotor reactivity (VMR) for the very first 30 min and then this effect disappears. And the high-frequency rTMS did not affect VMR at all. The effect of rTMS on VMR may continue up to 30 min but then return to the baseline and can be used safely.


Clinical and laboratory evaluation of penicillin resistant Streptococcus pneumoniae in relation to the mutations of pbp 1a, pbp2b and pbp2x.
A total of 210 isolates of Streptococcus pneumoniae (S. pneumoniae) were selected randomly to examine drug susceptibility which were obtained from out- and in-patients who visited Kurume University Hospital and other affiliated hospitals through May 1998 to September 1999. The prevalence of penicillin resistant S. pneumoniae in this study was 39.5% and was compatible with those of previous reports in Japan. From the clinical aspects, the resistant strains of S. pneumoniae have been shown not to be so highly virulent comparing with sensitive strains that only few severe or mortal cases had been reported. Carbapenems, glycopeptides, and fluoroquinolones were shown to be highly active against penicillin-resistant S. pneumoniae strains as evidenced by the low minimum inhibitory concentrations (MICs) though LVFX showed 4 micrograms/ml or higher MICs against some strains. Regarding to the mechanisms of penicillin resistance, penicillin binding proteins coding gene (pbp1a, pbp2x and pbp2b) mutations that cause modifications in these proteins were also examined for all isolates. The multivariate analysis showed statistically significant correlation between higher MIC of penicillin and cephem and pbp1a mutation while no significant contribution of pbp2x and pbp2b to the resistance was demonstrated. Additionally, no significant correlation between pbp mutation and MIC of carbapenem was observed. Furthermore, there were two highly penicillin resistant S. pneumoniae strains with no pbp mutations. Thus the pbp mutations alone were not responsible for the elevation of MIC all beta-lactams. Nevertheless the pbp mutations were detected in advance of actual MIC elevations by inducement experiment in vitro. It indicated that penicillin resistance might be detected earlier than conventional methods. In previous reports some other responsible genes for penicillin resistance were demonstrated. Therefore, it might be possible to presume exact values of MICs of beta-lactams against resistant strains of S. pneumoniae by detecting still unknown genes other than pbps.


[Personalized Treatment for Colorectal Carcinomas].
Colorectal carcinoma (CRC) is a major cause for cancer related death in Western countries. Particularly in the metastatic stage (mCRC) 5-year survival rate remains low at around 15 %. Treatment decisions are influenced by tumor stage, location of the primary, and extend of metastases. The multidisciplinary tumor board with an experienced hepato-biliary surgeon, an interventional radiologist, the medical oncologist, the molecular pathologist and the radiation oncologist will gain further importance in the quest for the optimal treatment for each patient. In the adjuvant setting, next to the established clinical risk factors, individualization especially for UICC-stage II patients can be done according to the CDX2-expression, the MSI-status, and perhaps the PIK3-status. In the metastatic stage, RAS and BRAF mutational analyses are pivotal to choose the best treatment for our patients. Primary tumor location in RAS-wild-type patients is further helping the clinician to tailor first-line treatment. Ongoing phase-III-trials will further help the clinician to come to a personalized decision.


The MG1363 and IL1403 laboratory strains of Lactococcus lactis and several dairy strains are diploid.
Bacteria are normally haploid, maintaining one copy of their genome in one circular chromosome. We have examined the cell cycle of laboratory strains of Lactococcus lactis, and, to our surprise, we found that some of these strains were born with two complete nonreplicating chromosomes. We determined the cellular content of DNA by flow cytometry and by radioactive labeling of the DNA. These strains thus fulfill the criterion of being diploid. Several dairy strains were also found to be diploid while a nondairy strain and several other dairy strains were haploid in slow-growing culture. The diploid and haploid strains differed in their sensitivity toward UV light, in their cell size, and in their D period, the period between termination of DNA replication and cell division.


Functional Conservation of LncRNA JPX Despite Sequence and Structural Divergence.
Long noncoding RNAs (lncRNAs) have been identified in all eukaryotes and are most abundant in the human genome. However, the functional importance and mechanisms of action for human lncRNAs are largely unknown. Using comparative sequence, structural, and functional analyses, we characterize the evolution and molecular function of human lncRNA JPX. We find that human JPX and its mouse homolog, lncRNA Jpx, have deep divergence in their nucleotide sequences and RNA secondary structures. Despite such differences, both lncRNAs demonstrate robust binding to CTCF, a protein that is central to Jpx's role in X chromosome inactivation. In addition, our functional rescue experiment using Jpx-deletion mutant cells shows that human JPX can functionally complement the loss of Jpx in mouse embryonic stem cells. Our findings support a model for functional conservation of lncRNAs independent from sequence and structural divergence. This study provides mechanistic insight into the evolution of lncRNA function.


The boundary value problem in spatial statistical analysis.
"The primary objective of this paper is to investigate procedures for detecting and handling existing border biasing in spatial statistical analysis." Six conventional solutions to the boundary value problem are criticized, and three alternate statistical solutions are proposed.


Babesia microti Immunoreactive Rhoptry-Associated Protein-1 Paralogs Are Ancestral Members of the Piroplasmid-Confined RAP-1 Family.
Babesia, Cytauxzoon and Theileria are tick-borne apicomplexan parasites of the order Piroplasmida, responsible for diseases in humans and animals. Members of the piroplasmid rhoptry-associated protein-1 (pRAP-1) family have a signature cysteine-rich domain and are important for parasite development. We propose that the closely linked B. microti genes annotated as BMR1_03g00947 and BMR1_03g00960 encode two paralogue pRAP-1-like proteins named BmIPA48 and Bm960. The two genes are tandemly arranged head to tail, highly expressed in blood stage parasites, syntenic to rap-1 genes of other piroplasmids, and share large portions of an almost identical ~225 bp sequence located in their 5' putative regulatory regions. BmIPA48 and Bm960 proteins contain a N-terminal signal peptide, share very low sequence identity (<13%) with pRAP-1 from other species, and harbor one or more transmembrane domains. Diversification of the piroplasmid-confined prap-1 family is characterized by amplification of genes, protein domains, and a high sequence polymorphism. This suggests a functional involvement of pRAP-1 at the parasite-host interface, possibly in parasite adhesion, attachment, and/or evasion of the host immune defenses. Both BmIPA48 and Bm960 are recognized by antibodies in sera from humans infected with B. microti and might be promising candidates for developing novel serodiagnosis and vaccines.


Antioxidant and Anti-Inflammatory Activity of Cynanchum acutum L. Isolated Flavonoids Using Experimentally Induced Type 2 Diabetes Mellitus: Biological and In Silico Investigation for NF-κB Pathway/miR-146a Expression Modulation.
Cynanchum acutum L. is a climbing vine that belongs to the family Apocynaceae. Using different chromatographic techniques, seven compounds were isolated from the methanolic extract of the plant. The isolated compounds include six flavonoid compounds identified as rutin (1), quercetin-3-O-neohesperidoside (2), quercetin-3-O-β-galactoside (3), isoquercitrin (4), quercetin (5), and kaempferol 3-O-β-glucoside (6), in addition to a coumarin, scopoletin (7). The structures of the compounds were elucidated based on 1D NMR spectroscopy and high-resolution mass spectrometry (HR-MS), and by comparison with data reported in the literature. The first five compounds were selected for in vivo investigation of their anti-inflammatory and antioxidant properties in a rat model of type 2 diabetes. All tested compounds significantly reduced oxidative stress and increased erythrocyte lysate levels of antioxidant enzymes, along with the amelioration of the serum levels of inflammatory markers. Upregulation of miR-146a expression and downregulation of nuclear factor kappa B (NF-κB) expression were detected in the liver and adipose tissue of rats treated with the isolated flavonoids. Results from the biological investigation and those from the validated molecular modeling approach on two biological targets of the NF-κB pathway managed to highlight the superior anti-inflammatory activity of quercetin-3-O-galactoside (3) and quercetin (5), as compared to other bioactive metabolites.


Thimet oligopeptidase and the stability of MHC class I epitopes in macrophage cytosol.
In this study we investigated the fate of a class of proteasome-generated oligopeptides, exposing them to the crude cytosol of macrophages or to the purified recombinant thimet oligopeptidase. Among the proteasome products of known sequences are MHC class I epitopes, 13 of which were randomly chosen to be used as putative substrates. Surprisingly, our results clearly showed that the majority of the peptides were poorly or not degraded, either by the purified enzyme or by the crude macrophage cytosol. The peptides, which were resistant to hydrolysis, displayed high affinity for the thimet oligopeptidase as competitive inhibitors. Regardless of the fact that our data do not allow prediction of whether or not a specific peptide would be degraded, it seems very likely that the structural features, which rule out the stability of the MHC class I peptides in the cytosol, may have implications in an optimized repertoire selection for antigen presentation.


How resource quality differentially affects motivation and ability to fight in hermit crabs.
Contesting animals typically gather information about the resource value and that information affects fight motivation. However, it is possible that particular resource characteristics alter the ability to fight independently of the motivation. Using hermit crabs, we investigate how the resource in terms of shell quality affects both motivation and ability to fight. These crabs fight for shells, but those shells have to be carried and may impose physiological costs that impede fight vigour. We find that the shell has different effects on motivation and ability. Potential attackers in very small shells were highly motivated to attack but, rather than having enhanced ability, unexpectedly quickly fatigued and subsequently were not more successful in the fights than were crabs in larger shells. We also examined whether defending crabs could gather information about the attacker's shell from the vigour of the attack. Defending crabs gave up quickly when a potential gain had been assessed, indicating that such information had been gathered. However, there was no indication that this could be owing to the activity of the attacker and the information is probably gathered via visual assessment of the shell.


Cayman Islands: cervical cancer increases.
A recent study of the incidence of cervical cancer in the Cayman Islands found that there had been a dramatic increase in the rate from 19.2/100,000 women during the first year of the 6 years studied to 62.6/100,000 women during the last year of the study. Well over 50% of the cases (58.6%) were women under the age of 40 years. 75% of the cases (75.9%) did not have a Pap smear within 5 years of the diagnosis. The mean annual age-adjusted incidence of cervical cancer during the study period was 42.7/100,000 women over 20 years of age, which is the highest reported incidence in the Caribbean. Further details of the study can be obtained from Dr. P. Maoris, George Twon Hospital, PO Box 915, Grand Cayman, Cayman Islands; phone: 0135 949 0190; e-mail: firstname.lastname@example.com


Associated risk factors of urinary tract infection among pregnant women at Felege Hiwot Referral Hospital, Bahir Dar, North West Ethiopia.
Urinary tract infections (UTIs) are among the most common bacterial infections in humans, both in the community and hospital settings. It is a serious health problem affecting millions of people each year and is the leading cause of Gram-negative bacteremia. We previously conducted a study on "Urinary Bacterial Profile and Antibiotic Susceptibility Pattern of UTI among Pregnant Women in North West Ethiopia" but the study did not address risk factors associated with urinary tract infection so the aim of the study was to assess associated risk factors of UTI among pregnant women in Felege Hiwot Referral Hospital, Bahir Dar, North West Ethiopia. A total of 367 pregnant women with and without symptoms of urinary tract infection(UTI) were included as a study subject from January 2011 to April 2011. Midstream urine samples were collected and processed following standard bacteriological tests. Data concerning associated risk factors were collected using structured questionnaires and were processed and analyzed using Statistical Package for Social Science (SPSS version 16). Bivarait analysis of socio-demographic characteristics and associated risk factors of UTI showed that family income level (family monthly income level ≤ 500 birr($37.85); P = 0.006, OR = 5.581, CI = 1.658, 18.793 and 501-1000 birr ($37.93-$75.70), P = 0.039, OR = 3.429, CI = 1.065, 11.034), anaemia (P = 0.003, OR = 4.388, CI = 1.776, 10.839), sexual activity (P = 0.032, OR = 3.520, CI = 1.197,10.363) and past history of UTI (P = 0.000, OR = 3.397, CI = 1.672, 6.902) were found to be factors significantly associated with increase prevalence of UTI. In contrast multiparity, history of catheterization, genitourinary abnormality, maternal age, gestational age and educational status were not significantly associated with UTI among pregnant women. In this study UTI was high among pregnant women in the presence of associated risk factor such as anaemia, low income level, past history of UTI and sexual activity.


Stepping over obstacles: dividing attention impairs performance of old more than young adults.
Tripping over an obstacle is a common cause of falls in the elderly. An earlier study of abilities to avoid stepping on suddenly appearing obstacles found that, although healthy old adults had a lower rate-of-success than young adults, the magnitude of that difference was not large. The present study inquired whether dividing attention during such a task would differentially affect young and old healthy adults. Rates-of-success were observed in 16 young and 16 old healthy adults (mean ages 24 and 72 years) in avoiding stepping on a band of light that was suddenly projected across their gait path while they walked at their comfortable gait speed. This virtual obstacle was placed at predicted next-footfall locations to give 350 or 450 msec available response times before footfall. During most of the trials the subjects were asked, in addition to trying not to step on the obstacle, simultaneously to respond vocally as quickly as possible when red lights near the end of the walkway turned on. These attention-dividing reaction time tests were of two types: synchronized, when only red lights lit at intervals synchronized with the appearance of the obstacle, and unsynchronized, when green or yellow lights lit in addition to the red lights, with lighting intervals not synchronized with the appearance of the obstacle. When synchronized and unsynchronized reaction time tests were conducted concurrently with the obstacle avoidance tasks, mean rates-of-success in avoidance decreased significantly in both young and old adults. With available response times of 350 msec, mean success rates decreased from their no-division values in the young adults by 14.7% for synchronized reaction and by 19.9% for unsynchronized reaction, attention-dividing tests. Corresponding mean decreases for the old adults were 32.0 and 35.7%. This age difference in the effects of dividing attention was significant. Both young and old adults had a significantly increased risk of obstacle contact while negotiating obstacles when their attention was divided, but dividing attention degraded obstacle avoidance abilities of the old significantly more than it did in the young. Diminished abilities to respond to physical hazards present in the environment when attention is directed elsewhere may partially account for high rates of falls among the elderly.


The effect of educational brochures on knowledge and emotional distress in women with abnormal Papanicolaou smears.
To determine whether an educational brochure about abnormal Papanicolaou smears could reduce psychological distress and concerns about cancer and future health, and increase knowledge about dysplasia and the investigation, treatment, and recommended follow-up. One hundred twenty-five consecutive women with dysplasia on a Papanicolaou smear referred to a colposcopy clinic for their first examination were alternately assigned to receive a mailed educational brochure the same day or to receive no brochure. At the colposcopy clinic, consenting women were given the Brief Symptom Inventory, specific questions about feelings regarding an abnormal smear, and a knowledge quiz about dysplasia, colposcopy, and the recommended follow-up. Women who received the brochure were significantly less distressed on the Brief Symptom Inventory and were less anxious about the abnormal Papanicolaou smear, the fear of cancer, and their future health than were women not receiving the brochure. Study women also performed significantly better on knowledge questions about dysplasia, colposcopy, and the recommended follow-up. Given the low cost, ease of delivery, and usefulness of educational brochures in reducing psychological distress and increasing knowledge specific to the condition, an educational brochure should routinely accompany or immediately follow notification about an abnormal Papanicolaou smear.


Incorporation of N-Methyl-d-glucamine Functionalized Oligomer into MIL-101(Cr) for Highly Efficient Removal of Boric Acid from Water.
Polymeric resins are practically important adsorbents in a wide variety of applications, but they generally suffer from low surface areas and limited functionalized adsorption sites owing to their closely compacted and tangled polymeric chains. A metal-organic framework (MOF)-polymer composite with enhanced adsorption capacity against the compacted polymeric resins was reported. The strategy to incorporate functionalized oligomer within the cavities of the MOF was demonstrated by the preparation of MIL-101(Cr) incorporated with N-methyl-d-glucamine-based organosiloxane polymer. The resulting MOF composite shows high efficiency for the removal of boric acid from water because of exceptionally high loading of functional groups responsible for the boron adsorption. This material offers promising perspectives for boron removal applications in seawater desalination.


Social, Cultural, and Environmental Challenges Faced by Children on Antiretroviral Therapy in Zimbabwe: a Mixed-Method Study.
Despite the advent of antiretroviral therapy (ART), many children, particularly in the rural communities of Zimbabwe, remain vulnerable. The purpose of this study was to determine the factors and challenges facing children on antiretroviral therapy (ART) in Brunapeg area of Mangwe District, Zimbabwe. A mixed-method approach involving interviewer-guided focus group discussions and piloted semi-structured questionnaires was utilized to collect data from different key population groups. The data obtained were analyzed through content coding procedures based on a set of predetermined themes of interest. A number of challenges emerged as barriers to the success of antiretroviral therapy for children. Primary care givers were less informed about HIV and AIDS issues for people having direct impact on the success of antiretroviral therapy in children whilst some were found to be taking the antiretroviral drugs meant for the children. It also emerged that some primary care givers were either too young or too old to care for the children while others had failed to disclose to the children why they frequently visited the Opportunistic Infections (OI) clinic. Most primary care givers were not the biological parents of the affected children. Other challenges included inadequate access to health services, inadequate food and nutrition and lack of access to clean water, good hygiene and sanitation. The lack of community support and stigma and discrimination affected their school attendance and hospital visits. All these factors contributed to non-adherence to antiretroviral drugs. Children on ART in rural communities in Zimbabwe remain severely compromised and have unique problems that need multi-intervention strategies both at policy and programmatic levels. Effective mitigating measures must be fully established and implemented in rural communities of developing countries in the fight for universal elimination of HIV/AIDS.


Adult attachment security and symptoms of depression: the mediating roles of dysfunctional attitudes and low self-esteem.
Three studies investigated the relation between adult attachment security and symptoms of depression. Study l examined the overall magnitude of the association between adult attachment and depression, and Studies 2 and 3 tested whether this relation was mediated by dysfunctional attitudes and low self-esteem. Results from the three studies were consistent with a mediation model. This model suggests that insecure adult attachment styles are associated with dysfunctional attitudes, which in turn predispose to lower levels of self-esteem. Such depletions in self-esteem are directly associated with increases in depressive symptoms over time. Insecure attachment appears to lead to depressive symptoms in adulthood through its impact on self-worth contingencies and self-esteem.


Usefulness of self-reported leisure-time physical activity to predict long-term survival in patients with coronary heart disease.
Self-reported leisure-time physical activity level correlates well with both cardiovascular (CV) and non-CV mortality in subjects without coronary heart disease (CHD). The impact of leisure-time physical activity on long-term outcomes has not been well studied in patients with preexisting CHD, who are often physically limited because of symptoms, medications, and co-morbid conditions. The aim was to determine the long-term prognostic value of self-reported leisure-time physical activity in a large CHD cohort. Leisure-time physical activity was evaluated using a self-administered questionnaire and categorized using a 4-level scale (sedentary, mild, moderate, and strenuous) in 14,021 of 24,958 subjects from the Coronary Artery Surgery Study Registry with suspected or proven CHD who underwent cardiac catheterization from 1974 to 1979. Median long-term follow-up was 14.7 years (interquartile range 9.8 to 16.2). Clinical outcomes were evaluated according to physical activity level and adjusted for potential confounders. Long-term all-cause and CV mortality progressively increased from most to least active subjects, with sedentary patients showing a 1.6-fold increase in mortality for both these outcomes (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.34 to 1.97, p <0.0001 for all-cause mortality). Similar trends were noted for men and women and in adjusted models, although HRs were attenuated after adjusting for age, gender, smoking, hypertension, diabetes mellitus, total cholesterol, body mass index, and ejection fraction (adjusted HR 1.23, 95% CI 1.01 to 1.49, p = 0.03 for all-cause mortality; adjusted HR 1.25, 95% CI 0.99 to 1.57, p = 0.05 for CV mortality). In conclusion, leisure-time physical activity independently predicted long-term survival in men and women with chronic stable CHD.


[Validation of the alcohol use disorders identification test (AUDIT) in Mexican patients with schizophrenia].
To validate the Alcohol Use Disorders Identification Test (AUDIT) in schizophrenic patients. The Composite International Diagnostic Interview (CIDI v. 1) and the AUDIT were administered to 80 subjects with schizophrenia, of both sexes, more than 16 years of age, from the outpatient services at the National Institute of Psychiatry in Mexico City. Of the 80 schizophrenic patients, 57 were men and 23 women, with a mean age of 30.5 years and 34.3 years, respectively; the age at schizophrenia onset was 22 years for men, and 26 years for women; 35 subjects (43.7%) were consumers of alcohol at the time of the study. The AUDIT scale showed high internal consistency with a Cronbach's alpha of 0.812; for this population, the cutoff point for the full AUDIT scale was 4 points or more; cutoff points for the AUDIT 'rapid test' and the 'psychosocial issues and probable alcohol dependence' were based on benchmarking against the CIDI (DSM-IIIR and ICD-10). The AUDIT validation showed it to be a useful and sensitive screening tool for identifying schizophrenic patients at risk for alcohol abuse and dependence; therefore, it is recommended for use in clinical and epidemiological studies in Latin America.


Investigating CFTR and KCa3.1 Protein/Protein Interactions.
In epithelia, Cl- channels play a prominent role in fluid and electrolyte transport. Of particular importance is the cAMP-dependent cystic fibrosis transmembrane conductance regulator Cl- channel (CFTR) with mutations of the CFTR encoding gene causing cystic fibrosis. The bulk transepithelial transport of Cl- ions and electrolytes needs however to be coupled to an increase in K+ conductance in order to recycle K+ and maintain an electrical driving force for anion exit across the apical membrane. In several epithelia, this K+ efflux is ensured by K+ channels, including KCa3.1, which is expressed at both the apical and basolateral membranes. We show here for the first time that CFTR and KCa3.1 can physically interact. We first performed a two-hybrid screen to identify which KCa3.1 cytosolic domains might mediate an interaction with CFTR. Our results showed that both the N-terminal fragment M1-M40 of KCa3.1 and part of the KCa3.1 calmodulin binding domain (residues L345-A400) interact with the NBD2 segment (G1237-Y1420) and C- region of CFTR (residues T1387-L1480), respectively. An association of CFTR and F508del-CFTR with KCa3.1 was further confirmed in co-immunoprecipitation experiments demonstrating the formation of immunoprecipitable CFTR/KCa3.1 complexes in CFBE cells. Co-expression of KCa3.1 and CFTR in HEK cells did not impact CFTR expression at the cell surface, and KCa3.1 trafficking appeared independent of CFTR stimulation. Finally, evidence is presented through cross-correlation spectroscopy measurements that KCa3.1 and CFTR colocalize at the plasma membrane and that KCa3.1 channels tend to aggregate consequent to an enhanced interaction with CFTR channels at the plasma membrane following an increase in intracellular Ca2+ concentration. Altogether, these results suggest 1) that the physical interaction KCa3.1/CFTR can occur early during the biogenesis of both proteins and 2) that KCa3.1 and CFTR form a dynamic complex, the formation of which depends on internal Ca2+.


Retrospection on the Role of Soluble Guanylate Cyclase in Parkinson's Disease.
Soluble guanylate cyclase (sGC) is an important transducing enzyme of cyclic guanosine monophosphate (cGMP) signaling pathway in striatum which has been considered as a potential target for the treatment of Parkinson's disease. Etiology of Parkinson's disease is multifactorial, finally resulting in abnormal proteinopathies causing degeneration of nigrostriatal pathways. Understanding the pathological basis of Parkinson's disease at molecular level is still an achievable target for the researchers and clinical practitioners. sGCs may be one of the causative factors resulting in Parkinson's disease due to glutamate toxicity or other event. This review presents the literature from articles of past five decades nearly as still this enzyme protein and its role in Parkinson's disease is not that clearly understood or presented till date. Recent interventions of this protein inhibition in the treatment of Parkinson's disease preclinically gave a chance to review the literature about this enzyme and its correlation with factors causing Parkinson's disease. We explored literature using PubMed and EMBASE for the role of sGC in Parkinson's disease. Databases were searched using the following terms: Parkinson's disease, neurotoxins, guanylate cyclase, sGC-cGMP pathway, and neurodegeneration. This review listed out the factors that have probability for stimulating sGC which already have been listed as a neurotoxins causing Parkinson's disease.


CNS prophylaxis for diffuse large B-cell lymphoma.
CNS relapse in the brain parenchyma, eyes, or leptomeninges is an uncommon but devastating complication of diffuse large B-cell lymphoma. CNS prophylaxis strategies, typically involving intrathecal or high-dose antimetabolites, have been developed in the front-line treatment setting with the aim to reduce this subsequent risk. Clinical and biological features associated with elevated risk are increasingly well defined and are discussed in this Review. This Review summarises both the historical and current developments in this challenging field, provides a nuanced discussion regarding current reasons for and against standard prophylactic measures, outlines evidence for the timing of prophylactic measures when delivered, and reflects on possible future developments.