Reliability and Validity of the Chinese Version of the Mild Behavioral Impairment Checklist for Screening for Alzheimer's Disease.
The Mild Behavioral Impairment Checklist (MBI-C), a screening scale for neuropsychiatric symptom evaluation, facilitates Alzheimer's disease (AD) screening. However, its validity and reliability for use as an AD screening tool have not been determined. To develop an AD screening scale suitable for the Chinese population. The MBI-C was translated into Chinese and back-translated with the original author's consent. Forty-six AD patients, attending the Xuanwu hospital memory clinic, and 50 sex- and education-matched controls from the community underwent a full neuropsychological evaluation, including MBI-C assessment. Among them, 15 AD patients were evaluated repeatedly, and eight were evaluated simultaneously by two different clinicians, to assess MBI-C reliability. The MBI-C demonstrated good internal consistency reliability, test-retest reliability, and inter-rater reliability. Its optimal cutoff point was 6/7 for identifying AD dementia, with a sensitivity of 86.96% and specificity of 86.00%, and its detection rate for moderate-severe AD dementia was higher than that of the Neuropsychiatric Inventory Questionnaire (NPI-Q). Pearson's correlation coefficients ranged from 0.702 to 0.831, indicating content validity. Seven factors were extracted during principal component analysis, with a cumulative contribution of 70.55%. Moreover, the Pearson's correlation coefficient was 0.758, indicating its criterion validity. The MBI-C could also distinguish AD dementia severity. MBI-C scores were significantly negatively correlated with MMSE and MoCA scores, and positively correlated with ADL scores. This study showed that the Chinese version of MBI-C has high reliability and validity, and could replace the NPI-Q for AD dementia screening in the Chinese population.


Broad Protection Against Clade 1 Sarbecoviruses After a Single Immunization with Cocktail Spike-Protein-Nanoparticle Vaccine.
The 2002 SARS outbreak, the 2019 emergence of COVID-19, and the continuing evolution of immune-evading SARS-CoV-2 variants together highlight the need for a broadly protective vaccine against ACE2-utilizing sarbecoviruses. While updated variant-matched formulations such as Pfizer-BioNTech's bivalent vaccine are a step in the right direction, protection needs to extend beyond SARS-CoV-2 and its variants to include SARS-like viruses. Here, we introduce bivalent and trivalent vaccine formulations using our spike protein nanoparticle platform that completely protected hamsters against BA.5 and XBB.1 challenges with no detectable virus in the lungs. The trivalent cocktails elicited highly neutralizing responses against all tested Omicron variants and the bat sarbecoviruses SHC014 and WIV1. Finally, our 614D/SHC014/XBB trivalent spike formulation completely protected human ACE2-transgenic hamsters against challenges with WIV1 and SHC014 with no detectable virus in the lungs. Collectively, these results illustrate that our trivalent protein-nanoparticle cocktail can provide broad protection against SARS-CoV-2-like and SARS-CoV-1-like sarbecoviruses.


Value of the different prognostic systems and biological markers for predicting severity and progression of acute pancreatitis.
Several tools have been developed for severity stratification in acute pancreatitis (AP). They include single biochemical markers and complex scoring systems, all of which aim at an early detection of severe AP to optimize monitoring and treatment of these patients. The aim of this study was to reassess and compare the value of some known and newly-introduced prognostic markers in the clinical context. We have conducted a prospective observational study. One hundred and eight patients with a diagnosis of AP and onset of the disease within last 72 h were included in this study. Clinical data and expression results of some serum biochemical markers were used for statistical analysis. The diagnostic performance of scores predicting severity and progression of AP, cut-off values, specificity, and sensitivity were established using receiver operating characteristic curve analysis. Among single biochemical markers, C-reactive protein remains the most useful. Despite its delayed increase, it is accurate, cheap, and widely available. Interleukin-6 and macrophage migration inhibitory factor seem to be new promising parameters for use in clinical routine. Pancreas specific scores (Imrie-Glasgow, pancreatitis outcome prediction) and scores assessing organ dysfunction (acute physiology and chronic health evaluation II, multiple organ dysfunction score, and Marshall score) remain of value in determining the severity, complications, and possible outcome of AP. Indication, timing, and consequences of the methods applied need to be carefully considered and incorporated into clinical assessments. Currently, there is no single prognostic marker that would cover the whole range of problems associated with the treatment of AP. The prediction of severity and progression of AP can be achieved using a series of accurate methods. The decision to undertake interventional or surgical treatment is the most complex task requiring both clinical judgment and meticulous monitoring of the patient.


Electron Microscope Autoradiography of Bacteria Labeled with Iodine-125.
The low-energy extranuclear electrons emitted by iodine-125 can be used for electron microscope autoradiography with results comparable to those obtained with tritium. Autoradiographs of tritium-labeled bacteria showed that 71 percent of all reacted grains localized on the cell. This figure was 86 percent when I(125)-labeled bacteria were used.


Ataxia rating scales are age-dependent in healthy children.
To investigate ataxia rating scales in children for reliability and the effect of age and sex. Three independent neuropaediatric observers cross-sectionally scored a set of paediatric ataxia rating scales in a group of 52 healthy children (26 males, 26 females) aged 4 to 16 years (mean age 10y 5mo SD 3y 11mo). The investigated scales involved the commonly applied International Cooperative Ataxia Rating Scale (ICARS), the Scale for Assessment and Rating of Ataxia (SARA), the Brief Ataxia Rating Scale (BARS), and PEG-board tests. We investigated the interrelatedness between individual ataxia scales, the influence of age and sex, inter- and intra-observer agreement, and test-retest reliability. Spearman's rank correlations revealed strong correlations between ICARS, SARA BARS, and PEG-board test (all p<0.001). ICARS, SARA, BARS and PEG-board test outcomes were age-dependent until 12.5, 10, 11, and 11.5 years of age respectively. Intraclass correlation coefficients (ICCs) varied between moderate and almost perfect (interobserver agreement: 0.85, 0.72, and 0.69; intraobserver agreement: 0.92, 0.94, and 0.70; and test-retest reliability: 0.95, 0.50, and 0.71; for ICARS, SARA, and BARS respectively). Interobserver variability decreased after the sixth year of life. In healthy children, ataxia rating scales are reliable, but should include age-dependent interpretation in children up to 12 years of age. To enable longitudinal interpretation of quantitative ataxia rating scales in children, European paediatric normative values are necessary.


Micro-RNA regulation of the mammalian lin-28 gene during neuronal differentiation of embryonal carcinoma cells.
Vertebrate genomes each encode hundreds of micro-RNAs (miRNAs), yet for few of these miRNAs is there empirical evidence as to which mRNA(s) they regulate. Here we report the identification of human lin-28 mRNA as a regulatory target of human miR-125b and its homolog miR-125a. Studies of miR-125b function in mouse P19 embryonal carcinoma cells induced to develop into neurons suggest a role for this regulatory miRNA in mammalian neuronal differentiation, since its increased concentration in these cells contributes to lin-28 downregulation. Within the lin-28 3' untranslated region (UTR) are two conserved miRNA responsive elements (miREs) that mediate repression by miR-125b and miR-125a. Simultaneous deletion of both miREs renders the lin-28 3' UTR almost completely insensitive to these miRNAs, indicating that these two miREs are the principal elements in the lin-28 3' UTR that respond to miR-125. At the 3' end of each element is an adenosine residue that makes a significant contribution to function irrespective of its complementarity to the 5'-terminal nucleotide of miR-125. By contrast to most earlier reports of gene repression by other miRNAs that are imperfectly complementary to their targets, lin-28 downregulation by miR-125 involves reductions in both translational efficiency and mRNA abundance. The decrease in the mRNA concentration is achieved by a posttranscriptional mechanism that is independent of the inhibitory effect on translation.


Free Radical and Nicotine Yields in Mainstream Smoke of Chinese Marketed Cigarettes: Variation with Smoking Regimens and Cigarette Brands.
Free radicals and nicotine are components of cigarette smoke that are thought to contribute to the development of smoking-induced diseases. China has the largest number of smokers in the world, yet little is known about the yields of tobacco smoke constituents in different Chinese brands of cigarettes. In this study, gas-phase and particulate-phase free radicals as well as nicotine yields were quantified in mainstream cigarette smoke from five popular Chinese brands and two research cigarettes (3R4F and 1R6F). Mainstream smoke was generated under International Organization of Standardization (ISO) and Canadian Intense (CI) smoking regimens using a linear smoking machine. Levels of free radicals and nicotine were measured by electron paramagnetic resonance spectroscopy (EPR) and gas chromatography with flame-ionization detection, respectively. Under the ISO puffing regimen, Chinese brand cigarettes produced an average of 3.0 ± 1.2 nmol/cig gas-phase radicals, 118 ± 44.7 pmol/cig particulate-phase radicals, and 0.6 ± 0.2 mg/cig nicotine. Under the CI puffing regimen, Chinese brand cigarettes produced an average of 5.6 ± 1.2 nmol/cig gas-phase radicals, 282 ± 92.1 pmol/cig particulate-phase radicals, and 2.1 ± 0.4 mg/cig nicotine. Overall, both gas- and particulate-phase free radicals were substantially lower compared to the research cigarettes under both regimens, whereas no significant differences were observed for nicotine levels. When Chinese brands were compared, the highest free radical and nicotine yields were found in "LL" and "BS" brands, while lowest levels were found in "YY". These results suggested that the lower radical delivery by Chinese cigarettes compared to United States reference cigarettes may be associated with reductions in oxidant-related harm.


The potential distribution of cassava mealybug (Phenacoccus manihoti), a threat to food security for the poor.
The cassava mealybug is a clear and present threat to the food security and livelihoods of some of the world's most impoverished citizens. Niche models, such as CLIMEX, are useful tools to indicate where and when such threats may extend, and can assist with planning for biosecurity and the management of pest invasions. They can also contribute to bioeconomic analyses that underpin the allocation of resources to alleviate poverty. Because species can invade and establish in areas with climates that are different from those that are found in their native range, it is essential to define robust range-limiting mechanisms in niche models. To avoid spurious results when applied to novel climates, it is necessary to employ cross-validation techniques spanning different knowledge domains (e.g., distribution data, experimental results, phenological observations). We build upon and update a CLIMEX niche model by Parsa et al. (PloS ONE 7: e47675), correcting inconsistent parameters and re-fitting it based on a careful examination of geographical distribution data and relevant literature. Further, we consider the role of irrigation, the known distribution of cassava production and a targeted review of satellite imagery to refine, validate and interpret our model and results. In so doing, we bring new insights into the potential spread of this invasive insect, enabling us to identify potential bio-security threats and biological control opportunities. The fit of the revised model is improved, particularly in relation to the wet and dry limits to establishment, and the parameter values are biologically plausible and accord with published scientific literature.


Combined use of in situ hybridization and unlabeled antibody peroxidase anti-peroxidase methods: simultaneous detection of type I procollagen mRNAs and factor VIII-related antigen epitopes in keloid tissue.
In this study, we developed methodology that allows the combined use of in situ hybridization and peroxidase anti-peroxidase techniques on the same tissue section. A human pro alpha 1(I) collagen cDNA and antibodies to factor VIII-related antigen were used on keloid tissue sections as a model for a fibrotic reaction. The basic protocols of the techniques were modified to obtain optimal results. The feasibility of this new method was demonstrated by elucidation of type I procollagen gene expression in the cells of blood vessel wall and the adjacent fibroblasts. In the case of capillaries, pro alpha 1(I) collagen mRNAs were detected within endothelial cells identified by the presence of factor VIII-related antigen. Pro alpha 1(I) collagen mRNAs were also found in close proximity of medium-size blood vessels, but in this context clearly outside the vessel wall. These results may contribute to the understanding of pathogenetic aspects of keloids and other fibrotic conditions. Thus, the combination of in situ hybridization and peroxidase anti-peroxidase techniques provides a useful tool to examine gene expression simultaneously both at mRNA and protein levels in fibrotic tissues. This methodology is also applicable to a variety of other biologic and pathologic situations.


Soluble blue as a counterstain in the Ziehl-Neelsen procedure--A brief communication.
A technique is described using soluble blue instead of the conventional methylene blue as a counterstain for the Ziehl-Neelsen procedure. This increases the intensity of blue staining of non-bacterial contaminants and is useful in monitoring the progress of purification of M. leprae from host tissue.


Scabies and genital herpes: a problem in management.
A patient who was infested with scabies subsequently developed recurrent herpes genitalis. Scratching the scabetic lesions resulted in self-inoculation with herpes on the lower abdomen and chin. Inoculation herpes is one of the most common complications of HSV-2 infection. The infection can be divided into primary, latent, shedding and recurrent stages. Pruritic lesions such as scabies complicate the management in herpes.


CT-guided percutaneous steroid injection for management of inflammatory arthropathy of the temporomandibular joint in children.
The purposes of this study were to retrospectively review an injection technique, to develop a grading system for evaluation of imaging findings, and to report preliminary outcome related to percutaneous CT-guided steroid injection into the temporomandibular joints of children with inflammatory arthropathy. CT-guided steroid injection into the temporomandibular joint of children with inflammatory arthropathy results in clinical and imaging improvement in a substantial proportion of children treated.


Novel role of microRNA-126 in digestive system cancers: From bench to bedside.
MicroRNAs (miRNAs) are ubiquitously expressed, small, non-coding RNAs that regulate the expression of approximately 30% of the human genes at the post-transcriptional level. miRNAs have emerged as crucial modulators in the initiation and progression of various diseases, including numerous cancer types. The high incidence rate of cancer and the large number of cancer-associated cases of mortality are mostly due to a lack of effective treatments and biomarkers for early diagnosis. Therefore there is an urgent requirement to further understand the underlying mechanisms of tumorigenesis. MicroRNA-126 (miR-126) is significantly downregulated in a number of tumor types and is commonly identified as a tumor suppressor in digestive system cancers (DSCs). miR-126 downregulates various oncogenes, including disintegrin and metalloproteinase domain-containing protein 9, v-crk sarcoma virus CT10 oncogene homolog and phosphoinositide-3-kinase regulatory subunit 2. These genes are involved in a number of tumor-associated signaling pathways, including angiogenesis, epithelial-mensenchymal transition and metastasis pathways. The aim of the current review was to summarize the role of miR-126 in DSCs, in terms of its dysregulation, target genes and associated signaling pathways. In addition, the current review has discussed the potential clinical application of miR-126 as a biomarker and therapeutic target for DSCs.


Structured Approach Therapy for Combat-Related PTSD in Returning U.S. Veterans: Complementary Mediation by Changes in Emotion Functioning.
To address the impact of combat-related posttraumatic stress disorder (PTSD) on U.S. Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans, the investigators developed a 12-session manualized PTSD treatment for couples called structured approach therapy (SAT). A randomized controlled trial had shown that 29 OEF/OIF veterans with combat-related PTSD who had participated in SAT showed significantly greater reductions in PTSD compared to 28 veterans receiving a 12-session PTSD family education intervention (Sautter, Glynn, Cretu, Senturk, & Vaught, 2015). We conducted supplemental follow-up and mediation analyses, which tested the hypothesis that changes in emotion functioning play a significant role in the decreases in PTSD symptoms primarily observed in veterans who had received SAT. Veterans assigned to the SAT condition showed significantly greater decreases than those assigned to PTSD family education in emotion regulation problems (p < .001, Cohen's f(2) = .18) and fear of intense emotions (p < .001, Cohen's f(2) = .152). Decreases in both emotion regulation problems (mediated effect:ab̂= .36), and fear of intense emotions (mediated effect:ab̂ = .24) were found to be complementary mediators of reductions in PTSD symptoms greater with SAT. These findings suggest that SAT may aid veterans in improving their ability to regulate trauma-related emotions.


Parasite communities of eels Anguilla anguilla in freshwater and marine habitats in Iceland in comparison with other parasite communities of eels in Europe.
Ninety-five eels from one marine and three freshwater localities in Iceland were examined for parasites. Twenty species were found, 12 from marine habitat, 12 from freshwater and 4 species were found in both habitats. These are: Eimeria anguillae, Chilodonella hexasticha, Trichodina fultoni, T. jadranica, Myxidium giardi, Myxobolus kotlani, two Zschokkella spp., Derogenes varicus, Deropristis inflata, Diplostonmum sp., Plagioporus angulatus, Podocotyle atomon, Anisakis simplex (larva), Eustrongylides sp. (larva), Hysterothylacium aduncum (larva), Raphidascaris acus (larval and adult stages), Bothriocephalus claviceps, Proteocephalus macrocephalus, and a pseudophyllidean larva. Thirteen of these species are new parasite records from Icelandic waters. The component community of marine eels was characterized by low diversity and a high dominance of a single species. Overall, seven species of helminths were observed, up to five different species occurring in an individual fish. The component community of the freshwater eels was species-poor with low diversity and relatively high dominance of single species. A between-sites difference in the freshwater eels was considerable; only Diplositonun sp. was found at more then one sampling site. Similar to previous studies, there is a total replacement of freshwater macroparasite species by marine ones in saline waters. But unlike research abroad in which species richness decreases with higher salinity, the marine eels in Iceland have considerably higher richness than the freshwater ones. The parasite communities of freshwater eels in Iceland are, in general species-poorer, less diverse and having higher Berger Parker (BP) dominance than other eel communities in Europe. Marine eels have on the other hand comparable species richness, are less diverse and with a high BP dominance.


Sex parties: female teen sexual experimentation.
Adolescent participants in a study aimed at exploring the nature and characteristics of girls' dating relationships revealed the phenomenon of sex parties. These teens defined a sex party as an opportunity to engage in sexual contact outside of typical dating relationships. Sexual activity could involve actual intercourse, but usually involved sex acts without vaginal intercourse. Data were collected through 22 semistructured interviews with female adolescents, ages 15-18. All the participants knew of sex parties, however, only a subgroup of these adolescents actually participated in activities loosely defined by teens as sex parties. Alcohol was common at these parties, but female teens asserted that they consumed alcohol willingly to relax, as opposed to being coerced to do so. Some teens expressed regret following participation in a sex party, although none reported sexual coercion or abuse.


Effects of phenylephrine on membrane currents in single smooth muscle cells of taenia caeci.
Procedures used for dissociation of taenia caeci smooth muscle cells usually damage alpha 1-adrenoceptors. This paper describes modes of isolation under which alpha 1-adrenoceptors of taenia caeci do not lose their function. It has been found that antioxidants (dithiothreitol or taurine) are able to protect receptors from injury caused by digestive enzymes. A high concentration of bovine serum albumin also protects receptors from enzyme injury if a relatively specific enzyme (collagenase Type XI, Sigma) is used. Phenylephrine (10 mcmol/l) studied both in muscle strips using the double sucrose gap method and in isolated smooth muscle cells using whole cell current clamp conditions substantially hyperpolarized the smooth muscle membrane. This hyperpolarization was blocked by pretreatment of the tissues or cells by prazosin (1 mcmol/l). Phenylephrine (1-50 mcmol/l), under whole cell patch clamp conditions, enhanced the frequency and amplitude of spontaneous transient outward currents (STOCs), which were voltage- and temperature-dependent, and elicited a low amplitude sustained outward current. Phenylephrine (10 mcmol/l) reduced the inward and enhanced the outward component of the total whole cell current evoked by voltage steps from the holding potential of -50 mV to -10 mV. Under experimental conditions when only calcium current was recorded, phenylephrine significantly enhanced its amplitude. These results are in favor of the assumption that phenylephrine induced hyperpolarization is at least partially the consequence of calcium influx, which activates potassium conductance.


Drug hypersensitivities: definition, epidemiology and risk factors.
Drug hypersensitivity reactions are the adverse effects of drugs taken at a dose which is tolerated by normal subjects, and which clinically resemble allergy. There is few true epidemiological data on drug hypersensitivity reactions. The available information requires a cautious interpretation as they are rarely proven. Both under diagnosis and over diagnosis must be taken into account. Drug hypersensitivity reactions represent one third of adverse drug reactions, can be life threatening and motivate changes on drug prescription. They concern more than 7% of the general population, therefore being an important public health problem. A few risk factors are already pinpointed. Future progress in genetics can help the identification of populations at risk for specific reactions. This review describes currently known data on incidence,prevalence, mor tality and risk factors of these reactions.


The effect of zirconia surface treatment on flexural strength and shear bond strength to a resin cement.
Despite the expanded applications for zirconia in restorative dentistry, there is no clear recommendation in the literature regarding surface treatment before bonding. The purpose of this study was to evaluate the effect of mechanical surface treatment of yttria-partially stabilized zirconia on its flexural strength and the effect of mechanical and chemical surface treatments on its bond strength to a resin cement. For flexural strength evaluation, zirconia bars (4 x 5 x 40 mm) were prepared from zirconia blocks, finished using a diamond rotary cutting instrument, sintered, then assigned into 4 groups: (1) control (no treatment), (2) airborne-particle abrasion, (3) silicoating, and (4) wet hand grinding. After storage for 24 hours at 37 degrees C, flexural strength was determined using a 3-point bending test, and the results were analyzed using 1-way ANOVA (alpha=.05). For shear bond strength evaluation, zirconia rods (2.5 x 3 mm) were prepared from zirconia blocks, sintered, and assigned into 16 groups. Each group underwent a combination of the following mechanical and chemical treatments. Mechanical treatment included: (1) control (no treatment), (2) airborne-particle abrasion, (3) silicoating, or (4) wet hand grinding. Chemical treatment included: (1) control (no treatment), (2) acid etching followed by silanation, (3) silanation only, or (4) application of zirconia primer. Dentin specimens were prepared from extracted molars stored in 0.5% chloramine-T. Zirconia rods were bonded to dentin using a resin cement (Multilink Automix), then light polymerized. After storage, the specimens were loaded to failure with the notched shear bond test method in a universal loading apparatus. For artificial aging analysis, the groups that achieved the highest bond strength values were duplicated, stored at 37 degrees C and 100% humidity for 90 days, and thermal cycled before being loaded to failure. Results were analyzed using 2-way ANOVA (alpha=.05). Airborne-particle abrasion and hand grinding significantly increased flexural strength. The highest shear bond strength values were achieved for the following groups: silicoated + silanated > hand ground + zirconia primer > airborne-particle abraded + silanated > zirconia primer > airborne-particle abraded + zirconia primer. Artificial aging resulted in significantly lower shear bond strength for the silicoated/silanated and the zirconia primer groups. Mechanical modification of the surface increased the flexural strength of Y-TZP. The resin bond to Y-TZP was improved by surface treatment. A combination of mechanical and chemical conditioning of the zirconia surface was essential to develop a durable resin bond to zirconia.


C9-mediated killing of bacterial cells by transferred C5b-8 complexes: transferred C5b-9 complexes are nonbactericidal.
The formation of the C5b-9 complex on the outer membrane of complement-sensitive cells of Escherichia coli results in inhibition of inner membrane function and the death of the cell. Cells bearing a precursor of the C5b-9 site, the C5b-8 complex, suffer no loss in viability. Antibiotic-sensitive, complement-sensitive donor cells bearing precursor C5b-8 complexes were incubated with equal numbers of antibiotic-resistant, complement-sensitive acceptor cells that had not been exposed to a complement source. This cell mixture was incubated with 5 mM EDTA for 5 min and then with calcium chloride (20 mM) for various times. The excess calcium ion concentration was effectively reduced with additional EDTA, and the cell mixture was washed and resuspended in buffer. The viability of the acceptor cells was assayed by plating on antibiotic-containing media. C9 was added to the mixture, and the mixture was incubated for 10 min at 37 degrees C and then plated as described above. It was found that the acceptor cells were killed by the addition of purified C9 only after incubation with donor cells bearing C5b-8 sites during the transfer procedure. This indicates that precursor C5b-8 sites that support C9-mediated killing could be transferred between cells. No loss in viability was detected for acceptor cells subjected to the procedure described above in the presence of donor cells bearing complete C5b-9 complexes, formed prior to mixing with acceptor cells for the transfer procedure.


A Comprehensive Risk Analysis of Transportation Networks Affected by Rainfall-Induced Multihazards.
Climate change and its projected natural hazards have an adverse impact on the functionality and operation of transportation infrastructure systems. This study presents a comprehensive framework to analyze the risk to transportation infrastructure networks that are affected by natural hazards. The proposed risk analysis method considers both the failure probability of infrastructure components and the expected infrastructure network efficiency and capacity loss due to component failure. This comprehensive approach facilitates the identification of high-risk network links in terms of not only their susceptibility to natural hazards but also their overall impact on the network. The Chinese national rail system and its exposure to rainfall-related multihazards are used as a case study. The importance of various links is comprehensively assessed from the perspectives of topological, efficiency, and capacity criticality. Risk maps of the national railway system are generated, which can guide decisive action regarding investments in preventative and adaptive measures to reduce risk.


Neuronal release of D-serine: a physiological pathway controlling extracellular D-serine concentration.
D-serine is thought to be a glia-derived transmitter that activates N-methyl D-aspartate receptors (NMDARs) in the brain. Here, we investigate the pathways for D-serine release using primary cultures, brain slices, and in vivo microdialysis. In contrast with the notion that D-serine is exclusively released from astrocytes, we found that D-serine is released by neuronal depolarization both in vitro and in vivo. Veratridine (50 microM) or depolarization by 40 mM KCl elicits a significant release of endogenous D-serine from primary neuronal cultures. Controls with astrocyte cultures indicate that glial cells are insensitive to veratridine, but release D-serine mainly by the opening of volume-regulated anion channels. In cortical slices perfused with veratridine, endogenous D-serine release is 10-fold higher than glutamate receptor-evoked release. Release of D-serine from slices does not require internal or external Ca(2+), suggesting a nonvesicular release mechanism. To confirm the neuronal origin of D-serine, we selectively loaded neurons in cortical slices with D-[(3)H]serine or applied D-alanine, which specifically releases D-serine from neurons. Depolarization with veratridine promotes D-serine release in vivo monitored by high temporal resolution microdialysis of the striatum. Our data indicate that the neuronal pool of D-serine plays a major role in D-serine dynamics, with implications for the regulation of NMDAR transmission.


Membrane-bound neomycin phosphotransferase confers drug-resistance in mammalian cells: a marker for high-efficiency targeting of genes encoding secreted and cell-surface proteins.
An efficient method for inactivating genes is the use of silent selectable markers that are expressed only after homologous recombination into the active target gene. However, use of this approach for genes encoding secreted or membrane-anchored proteins may produce hybrid proteins comprising the N-terminal signal sequence from the target gene linked to the protein conferring drug resistance. Such chimeric enzymes will be secreted, precluding selection for drug resistance. To overcome this problem, we tested the possibility of anchoring in the membrane the cytoplasmic neomycin phosphotransferase (NPT). We constructed a fusion gene with a transmembrane domain connecting the N-terminal signal sequence of a membrane-targeted protein and the neo gene. Expression of this gene yielded G418-resistant colonies of C2C12 cells which contained assayable NPT activity. Comparison of enzyme activity in cell extract fractions verified that the active fusion protein was insoluble, presumably through localization to a membrane compartment. Transmembrane neo cassettes should serve as integration-activated markers capable of targeting genes encoding secreted or cell surface proteins.


The first report on mushroom green mould disease in Croatia.
Green mould disease, caused by Trichoderma species, is a severe problem for mushroom growers worldwide, including Croatia. Trichoderma strains were isolated from green mould-affected Agaricus bisporus (button or common mushroom) compost and Pleurotus ostreatus (oyster mushroom) substrate samples collected from Croatian mushroom farms. The causal agents of green mould disease in the oyster mushroom were T. pleurotum and T. pleuroticola, similar to other countries. At the same time, the pathogen of A. bisporus was exclusively the species T. harzianum, which is different from earlier findings and indicates that the range of mushroom pathogens is widening. The temperature profiles of the isolates and their hosts overlapped, thus no range was found that would allow optimal growth of the mushrooms without mould contamination. Ferulic acid and certain phenolic compounds, such as thymol showed remarkable fungistatic effect on the Trichoderma isolates, but inhibited the host mushrooms as well. However, commercial fungicides prochloraz and carbendazim were effective agents for pest management. This is the first report on green mould disease of cultivated mushrooms in Croatia.


Amino-Termination of Silicon Carbide Nanoparticles.
Silicon carbide nanoparticles (SiC NPs) are promising inorganic molecular-sized fluorescent biomarkers. It is imperative to develop methods to functionalize SiC NPs for certain biological applications. One possible route is to form amino groups on the surface, which can be readily used to attach target biomolecules. Here, we report direct amino-termination of aqueous SiC NPs. We demonstrate the applicability of the amino-terminated SiC NPs by attaching bovine serum albumin as a model for functionalization. We monitor the optical properties of the SiC NPs in this process and find that the fluorescence intensity is very sensitive to surface termination. Our finding may have implications for a few nanometers sized SiC NPs containing paramagnetic color centers with optically read electron spins.


Gender difference in cardiovagal baroreflex gain in humans.
We tested the hypothesis that women would demonstrate lower cardiovagal baroreflex gain compared with men. If so, we further hypothesized that the lower cardiovagal baroreflex gain in women would be associated with their lower aerobic fitness and higher body fat percentage compared with men. To accomplish this, we measured cardiovagal baroreflex gain (modified Oxford technique) in sedentary, nonobese (body mass index < 25 kg/m2) men (age = 26.0 +/- 2.1 yr, n = 11) and women (age = 26.9 +/- 1.6 yr, n = 14). Resting R-R interval and diastolic blood pressure were similar in the two groups, but systolic blood pressure was lower (P < 0.05) in the women. Cardiovagal baroreflex gain was significantly lower in the women compared with the men (13.3 +/- 1.5 vs. 20.0 +/- 2.8 ms/mmHg, P < 0.05). The lower cardiovagal baroreflex gain in the women was not related (P > 0.05) to their lower aerobic fitness and was only marginally related to their higher body fat percentage (r = -0.34, P < 0.05). There were no gender differences in the threshold and saturation, operating range, or operating point (all P > 0.05), although the operating point fell significantly to left (i.e., at a lower systolic blood pressure) compared with men. Therefore, the findings of this study suggest that the gain of the cardiovagal baroreflex is reduced whereas other parameters were similar in women compared with men. The mechanisms responsible for the reduced cardiovagal baroreflex gain remain unclear.


Response of CH4 emission of paddy fields to land management practices at a microcosmic cultivation scale in China.
The terrestrial ecosystem may be either a source or a sink of CH4 in rice paddies, depending, to a great extent, on the change of ecosystem types and land use patterns. CH4 emission fluxes from paddy fields under 4 cultivation patterns (conventional plain culture of rice (T1), no-tillage and ridge culture of rice (T2), no-tillage and ridge culture of rice and wheat (T3), and rice-wheat rotation (T4)) were measured with the closed chamber technique in 1996 and 1998 in Chongqing, China. The results showed that differences existed in CH4 emission from paddy fields under these land management practices. In 1996 and 1998, CH4 emission was 71.48% and 78.82% (T2), 65.93% and 57.18% (T3), and 61.53% and 34.22% (T4) of that in T1 during the rice growing season. During the non-rice growing season, CH4 emission from rice fields was 76.23% in T2 and 38.69% in TI. The accumulated annual CH4 emission in T2, T3 and T4 in 1996 decreased by 33.53%, 63.30% and 65.73%, respectively, as compared with that in T1. In 1998, the accumulated annual CH4 emission in T1, T2, T3 and T4 was 116.96 g/m2, 68.44 g/m2, 19.70 g/m2 and 11.80 g/m2, respectively. Changes in soil physical and chemical properties, in thermal and moisture conditions in the soil and in rice plant growth induced by different land use patterns were the dominant causes for the difference in CH4 emission observed. The relative contribution of various influencing factors to CH4 emission from paddy fields differed significantly under different land use patterns. However, the general trend was that chlorophyll content in rice leaves, air temperature and temperature at the 5 cm soil layer play a major role in CH4 emission from paddy fields and the effects of illumination, relative humidity and water layer depth in the paddy field and CH4 concentration in the crop canopy were relatively non-significant. Such conservative land use patterns as no-tillage and ridge culture of rice with or without rotation with wheat are thought to be beneficial to reducing CH4 emission from paddy fields and are, therefore, recommended as a significant solution to the problems of global (climatic) change.


Entanglement generation using silicon photonic wire waveguide.
This paper reviews recent progress on telecom-band entangled photon-pair sources based on spontaneous four-wave mixing (SFWM) in a silicon photonic wire waveguide. Thanks to the large third order nonlinearity of nano-scale silicon waveguides, we can generate photon pairs efficiently. Moreover, the use of silicon waveguides enable us to avoid the noise photons caused by spontaneous Raman scattering, which has been a serious problem with entanglement sources based on SFWM in dispersion shifted fiber. We successfully demonstrated high-purity time-bin and polarization entanglement generation using 1-cm long silicon waveguides.


Nanoscale Fluid Vortices and Nonlinear Electroosmotic Flow Drive Ion Current Rectification in the Presence of Concentration Gradients.
Ion current rectification (ICR) is a transport phenomenon in which an electrolyte conducts unequal currents at equal and opposite voltages. Here, we show that nanoscale fluid vortices and nonlinear electroosmotic flow (EOF) drive ICR in the presence of concentration gradients. The same EOF can yield negative differential resistance (NDR), in which current decreases with increasing voltage. A finite element model quantitatively reproduces experimental ICR and NDR recorded across glass nanopipettes under concentration gradients. The model demonstrates that spatial variations of electrical double layer properties induce the nanoscale vortices and nonlinear EOF. Experiments are performed in conditions directly related to scanning probe imaging and show that quantitative understanding of nanoscale transport under concentration gradients requires accounting for EOF. This characterization of nanopipette transport physics will benefit diverse experimentation, pushing the resolution limits of chemical and biophysical recordings.


Magnetoencephalography: evidence of magnetic fields produced by alpha-rhythm currents.
Weak alternating magnetic fields outside the human scalp, produced by alpha-rhythm currents, are demonstrated. Subject ard magnetic detector were housed in a multilayer magnetically shielded chamber. Background magnetic noise was reduced by signal-averaging. The fields near the scalp are about 1 x 10(-9) gauss (peak to peak). A course distribution shows left-right symmetry for the particular averaging technique used here.


Chromosomal origin of acetyltransferase AAC(6') specifying amikacin resistance in Serratia marcescens.
Two clinical isolates of Serratia marcescens resistant to aminoglycoside-aminocyclitols and other antibiotics have been examined for aminoglycoside-modifying enzymes. Both strains were amikacin-resistant, and this resistance was mediated by an acetyltransferase AAC(6'). S. marcescens 737 contains a single conjugative plasmid, pUZ 737, of 135 kilobases, which confers resistance to gentamicin and tobramycin by a nucleotidyltransferase, ANT(2"), and to kanamycin, neomycin, butirosin and lividomycin by a phosphotransferase, APH(3'). S. marcescens 1830 does not contain extrachromosomal DNA, and it produced only the above mentioned AAC(6'). The presence of AAC(6') and associated aminoglycoside resistance are not dependent on the presence of a detectable plasmid, not transferred by conjugation, and not cured. Therefore, this enzyme is probably encoded by a chromosomal gene.


Emerging cephalosporin and multidrug-resistant gonorrhoea in Europe.
Neisseria gonorrhoeae has consistently developed resistance to antimicrobials used therapeutically for gonorrhoea and few antimicrobials remain for effective empiric first-line therapy. Since 2009 the European gonococcal antimicrobial surveillance programme (Euro-GASP) has been running as a sentinel surveillance system across Member States of the European Union (EU) and European Economic Area (EEA) to monitor antimicrobial susceptibility in N. gonorrhoeae. During 2011, N. gonorrhoeae isolates were collected from 21 participating countries, and 7.6% and 0.5% of the examined gonococcal isolates had in vitro resistance to cefixime and ceftriaxone, respectively. The rate of ciprofloxacin and azithromycin resistance was 48.7% and 5.3%, respectively. Two (0.1%) isolates displayed high-level resistance to azithromycin, i.e. a minimum inhibitory concentration (MIC) ≥256 mg/L. The current report further highlights the public health need to implement the European response plan, including further strengthening of Euro-GASP, to control and manage the threat of multidrug resistant N. gonorrhoeae.


Update/Review: changing of use of local anesthesia in the hand.
Among the many advances in local anesthesia of the hand, some of the most significant changes in the last 5 years have been the following: (1) the acceptance of safety of locally infiltrated epinephrine with lidocaine for hemostasis, which has removed the need for sedation, brachial plexus blocks, and general anesthesia for most common hand surgery operations and minor hand trauma. (2) The elimination of the 2 injection finger block technique in favor of the single injection palmar block. (3) Local anesthesia can now be consistently injected in the hand with minimal pain. (4) Liposomal release of local anesthetic after injection into the surgical site can provide pain control up to 3 days. This article reviews the impact and best evidence related to these changes.


Urinary albumin excretion and insulin metabolism in clinically healthy 58-year-old men.
The aim of the present cross-sectional study was to investigate the relationship between urinary albumin excretion and insulin sensitivity, intact insulin and insulin propeptides in 104 clinically healthy 58-year-old men recruited from the general population. Insulin sensitivity (hyperinsulinemic euglycemic clamp) adjusted for lean body mass, fasting plasma insulin, proinsulin, split-proinsulin, C-peptide, and urinary albumin excretion and were determined. Urinary albumin excretion was significantly associated with body mass index (BMI), systolic and diastolic blood pressure, plasma insulin, and C-peptide (P <.05). Insulin sensitivity tended to be associated with urinary albumin excretion (P=.07). In a multiple regression analysis, urinary albumin excretion was independently and significantly associated with systolic blood pressure (P <.05). In conclusion, urinary albumin excretion was associated with insulin and C-peptide in clinically healthy 58-year-old men; however, this relationship became insignificant when blood pressure was taken into account in the regression analysis.


MicroRNAs, long noncoding RNAs, and circular RNAs: potential tumor biomarkers and targets for colorectal cancer.
Noncoding RNAs (ncRNAs) can be divided into microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), pRNAs, and tRNAs. Traditionally, miRNAs exert their biological function mainly through the inhibition of translation via the induction of target RNA transcript degradation. lncRNAs and circRNAs were once considered to have no potential to code proteins. Here, we will review the current knowledge on ncRNAs in relation to their origins, characteristics, and functions. We will also review how ncRNAs work as competitive endogenous RNA, gene transcription and expression regulators, and RNA-binding protein sponges in colorectal cancer (CRC). Notably, except for the abovementioned mechanisms, recent advances revealed that lncRNAs can also act as the precursor of miRNAs, and a small portion of lncRNAs and circRNAs was verified to have the potential to code proteins, providing new evidence for the significance of ncRNAs in CRC tumorigenesis and development.


Localized infection and leg ulcer after platelet-rich plasma injection.
Although many studies report effective use of platelet-rich plasma (PRP) injection in the clinics, almost no study reports any side effects. The patient who was treated with PRP injection in gastrocnemius muscle developed complications. The authors of this study present a case which may show the possible side effects of PRP.


Prognostic indicators in patients with primary intraventricular haemorrhage.
Primary intraventricular haemorrhage (PIVH) is a rare clinical entity. We sought to evaluate risk factors, clinical and radiological features, and outcome of patients with PIVH. Cases of PIVH were identified from cohort of patients with non traumatic intracerebral haemorrhage (ICH) by reviewing the radiological data. Their charts were reviewed and demographic, clinical, radiological and laboratory data was recorded and analyzed. Chi square and t test were used to determine predictors of poor outcome. Fifteen of 677 (2%) patients with ICH had PIVH. Nine (60%) were men. Median age was 56 years. Predisposing factors included hypertension in twelve (80%), coagulopathy in five (33%) and vascular malformations in two (13%) patients. Eleven (73%) patients developed hydrocephalus. Two patients died. Univariate analysis identified diabetes mellitus, blood in all ventricles and coagulopathy as predictors of death during initial hospital stay and hydrocephalus as predictor of poor outcome (death and disability combined) (p < 0.05). Hypertension is most common associated risk factor for primary intraventricular haemorrhage followed by coagulopathy. Hydrocephalus is a common complication, associated with poor outcome. Diabetes mellitus, coagulopathy and panventricular blood predict early mortality.


Increase in adhesion molecules on CD4+ cells and CD4+ cell subsets in synovial fluid from patients with rheumatoid arthritis.
To elucidate the role of adhesion molecules in the pathogenesis of rheumatoid arthritis (RA). We evaluated their expression and that of an activation marker on CD4+ cell populations and CD4+ cell subsets in specimens of peripheral blood (PB) and synovial fluid (SF) obtained from 10 patients with RA and 7 with osteoarthritis (OA). A 2 or 3-color immunofluorescent method was used for analysis. The SF from both groups of patients showed a greater density of adhesion molecules including LFA-1 alpha, LFA-1 beta, CD2, VLA-4 alpha and VLA-5 alpha on CD4+ cells, and a higher percentage of CD4+HLA-DR+ cells compared with their PB. IN PB-CD4+ cell subsets from the arthritic and healthy subjects, the CD4+CD45RO+ cell population showed an increased expression of adhesion molecules compared with CD4+CD45RA+ cell population. The expression of adhesion molecules on circulating CD4+ cell population and CD4+ cell subsets from the patients with RA and OA was comparable to that from healthy subjects. SF from both groups of patients showed a higher percentage of CD4+CD45RO+ cells and a lower percentage of CD4+CD45RA+ cells. In SF-CD4+ cell subsets from patients with RA, the CD4+CD45RO+ cell population had an increased expression of VLA-4 alpha compared to the CD4+CD45RA+ cell population; however, there was no significant difference in other adhesion molecule expression and the percentage of HLA-DR+ cells between the 2 cell subsets. Furthermore, the expression of VLA-4 alpha on the CD4+CD45RO+ cell population in SF from patients with RA was significantly higher than that in matched PB. In CD4+CD45RA+ cell population from both groups of patients, SF showed an enhanced expression of adhesion molecules and an increased percentage of HLA-DR+ cells compared with matched PB. Our results suggest that increased expression of adhesion molecules and increased percentage of HLA-DR+ cells on CD4+ cells in SF may be responsible for cellular interactions between these cells and synovial cells or extracellular matrix.


Avulsion injuries: an update on radiologic findings.
Avulsion injuries result from the application of a tensile force to a musculoskeletal unit or ligament. Although injuries tend to occur more commonly in skeletally immature populations due to the weakness of their apophysis, adults may also be subject to avulsion fractures, particularly those with osteoporotic bones. The most common sites of avulsion injuries in adolescents and children are apophyses of the pelvis and knee. In adults, avulsion injuries commonly occur within the tendon due to underlying degeneration or tendinosis. However, any location can be involved in avulsion injuries. Radiography is the first imaging modality to diagnose avulsion injury, although advanced imaging modalities are occasionally required to identify subtle lesions or to fully delineate the extent of the injury. Ultrasonography has a high spatial resolution with a dynamic assessment potential and allows the comparison of a bone avulsion with the opposite side. Computed tomography is more sensitive for depicting a tiny osseous fragment located adjacent to the expected attachment site of a ligament, tendon, or capsule. Moreover, magnetic resonance imaging is the best imaging modality for the evaluation of soft tissue abnormalities, especially the affected muscles, tendons, and ligaments. Acute avulsion injuries usually manifest as avulsed bone fragments. In contrast, chronic injuries can easily mimic other disease processes, such as infections or neoplasms. Therefore, recognizing the vulnerable sites and characteristic imaging features of avulsion fractures would be helpful in ensuring accurate diagnosis and appropriate patient management. To this end, familiarity with musculoskeletal anatomy and mechanism of injury is necessary.


Canonical and non-canonical adenosinergic pathways.
Adenosine (ADO) is an immunosuppressive molecule with multiple functions in different human organs. ADO is released through the concerted action of surface molecules endowed with enzymatic functions, that belong to two different adenosinergic pathways. The canonical pathway is started by CD39, that converts ATP to AMP. On the other hand, the non-canonical pathway metabolizes NAD+ to ADPR, through the action of CD38. The latter byproduct is then converted to AMP by CD203a/PC-1. Both pathways converge to CD73, that fully degrades AMP to the final product ADO. In this Review we take into account the most relevant finding regarding the expression of ectoenzymes belonging to both adenosinergic pathways in different cell types, including regulatory cell subsets and neoplastic cells. Moreover, we summarize the role of these molecules in different physiological and pathological settings. Finally, we discuss potential therapeutic application of specific inhibitors of ectoenzymes and/or ADO receptors.


The type I IFN signature as a biomarker of preclinical rheumatoid arthritis.
To validate the presence and demonstrate the clinical value of the type I interferon (IFN)-signature during arthritis development. In 115 seropositive arthralgia patients who were followed for the development of arthritis (Amsterdam Reade cohort), and 25 presymptomatic individuals who developed rheumatoid arthritis (RA) later, and 45 population-based controls (Northern Sweden cohort), the expression levels of 7 type I IFN response genes were determined with multiplex qPCR and an IFN-score was calculated. The diagnostic performance of the IFN-score was evaluated using Cox regression and Receiver Operating Characteristics (ROC)-curve analysis. In 44 of the 115 at-risk individuals (38%) from the Amsterdam Reade cohort, arthritis developed after a median period of 8 months (IQR 5-13). Stratification of these individuals based on the IFN-score revealed that 15 out of 25 IFN(high) individuals converted to arthritis, compared with 29 out of 90 IFN(low) individuals (p=0.011). In the Northern Sweden cohort, the level of the IFN-score was also significantly increased in presymptomatic individuals who developed RA compared with population-based controls (p=0.002). Cox regression analysis of the Amsterdam Reade cohort showed that the hazard ratio (HR) for development of arthritis was 2.38 (p=0.008) for IFN(high) at-risk individuals after correction for anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF). The ROC-curve area under the curve (AUC) for the IFN-score combined with ACPA and RF in the prediction of arthritis was 78.5% (p=0.0001, 95% CI 0.70 to 0.87). The results demonstrated clinical utility for the IFN-signature as a biomarker in the prediction of arthritis development.


Consecutive Case Series of Uniportal Full-endoscopic Unilateral Laminotomy for Bilateral Decompression in Lumbar Spinal Stenosis: Relationship between Decompression Range and Functional Outcomes.
Uniportal full-endoscopic unilateral laminotomy for bilateral decompression (UFE-ULBD) has been used to treat lumbar spinal stenosis (LSS) with satisfactory outcomes. However, a limited number of studies have investigated the relationship between decompression range and clinical outcomes. This study aimed to investigate the efficacy of UFE-ULBD for single-segment LSS and to explore the relationship between the decompression range and functional outcomes. Single-segment LSS patients who had undergone UFE-ULBD using an interlaminar approach between November 2021 and February 2023 were retrospectively analyzed. Patient demographics, visual analogue scale (VAS) scores for leg and back pain, Oswestry disability index (ODI) scores, modified MacNab grades, and radiological outcomes, including the decompression ratio of the disc-flava ligament space and osseous lateral recess, the enlargement ratio of superior articular process interval, lamina interval dural sac cross-sectional area (DSCA), were collected. The independent sample t-tests, paired sample t-tests, chi-square tests, Fisher's exact tests, and Pearson's and Spearman's correlation analyses were used. Forty patients (23 males, and 17 females) were retrospectively enrolled in this study. The mean follow-up period was 12 months. At the last follow-up, VAS scores for leg pain and back pain decreased from 6.0 ± 0.8 to 1.0 ± 1.9 (p < 0.001), and from 6.0 ± 0.8 to 1.2 ± 1.8 (p < 0.001) respectively; ODI score decreased from 71.7 ± 6.2 to 24.3 ± 21.3 (p < 0.001). According to the modified MacNab criteria, the results were excellent in 28 (70%), good in 5 (12.5%), fair in 6 (15%), and poor in 1 (2.5%), with an excellent-good rate of 82.5%. The postoperative DSCA enlarged from 57.69 ± 21.86 to 150.75 ± 39.33 mm2 (p < 0.001), with an enlargement ratio of 189.43 ± 107.83%. No difference in clinical or radiological parameters was detected between patients with excellent, good, fair, or poor outcomes based on the modified MacNab criteria. UFE-ULBD can provide satisfactory clinical and radiological outcomes in single-segment LSS patients. With sufficient exposure to the dural sac boundary, the functional outcome was not related to the radiological decompression range in LSS patients who had undergone UFE-ULBD.


Frequency of epstein-barr virus in classical hodgkin Lymphoma.
Epstein-Barr virus plays an important role in pathogenesis of Hodgkin lymphoma. The first patient with Epstein-Barr positive Reed Sternberg cells was described in 1985. Since then association between Epstein-Barr virus and Hodgkin lymphoma has been shown in many parts of the world and its occurrence shows significant variation from continent to continent and from country to country. The study was carried out at department of histopathology, Armed Forces Institute of Pathology from 27th April 2013 to 10th March 2014. A total of 55 cases of classical Hodgkin lymphoma were included in the study. Out of 55 patients, 38 (69%) were male and 17 (31%) were female. The age of the patients ranged between 4-67 years with an average age of 29.4±21.72 years. Out of these, 44 cases (80%) were positive for latent membrane protein-1. Among positive cases 32 (72.72%) were male and 12 (27.28%) were female. Based upon histological subtypes MCHL was the commonest as a whole accounting for 87.3% as well as among both genders. Out of total 55 cases, 79.16% (38/48) of mixed cellularity Hodgkin lymphoma cases showed positivity for latent membrane protein-1 while 83.33% (5/6) cases of nodular sclerosis Hodgkin lymphoma and 100% (1/1) cases of lymphocyte depleted Hodgkin lymphoma showed positivity. No case of lymphocyte predominant classical Hodgkin lymphoma was diagnosed during the study. 80% of our classical Hodgkin lymphoma cases showed association with EBV expression. A total of 79.16% cases of mixed cellularity Hodgkin lymphoma showed LMP1 expression while 100% of lymphocyte depleted Hodgkin lymphoma showed LMP1 expression. The highest expression seen in lymphocyte depleted Hodgkin lymphoma subtype in contrast to mixed cellularity requires to be confirmed by a larger scale study comprising of substantial number of patients of lymphocyte depleted Hodgkin lymphoma and lymphocyte rich classical Hodgkin lymphoma.


Low- and high-level controlled processing in executive motor control tasks in 5-6-year-old children at risk of ADHD.
The scant research on the characteristics of Attention-Deficit/Hyperactivity Disorder (ADHD) in kindergarten years curtails progress on early assessment of ADHD. By screening a general population sample of 1317 five- to six-year-old children, four groups of children were selected. The performance of 30 children later diagnosed with ADHD was compared with 74 children later diagnosed with 'borderline ADHD' (children exhibiting all ADHD symptoms but without disruptions on two situations), 113 children later diagnosed with other psychopathology, and 126 healthy controls on computerised motor control tasks involving low- and high-level controlled processing. In addition, motor control was compared with movement speed. The children at risk of ADHD were in general less accurate and more variable in their movements than the children with other psychopathology and healthy controls. Under conditions of high-level controlled processing, the children at risk of ADHD were disproportionately more inaccurate and had a more unstable performance with their preferred hand than the other children. In addition, linear effects were found, with the children at risk of ADHD having the worst performance, followed by the children with 'borderline ADHD', and then both groups of control children. No significant group differences were found in movement speed. The main findings are interpreted as evidence for a specific deficit in high-level controlled processing in young children at risk of ADHD, now found in a motor task, rather than a response task. Furthermore, the results support the notion that ADHD represents a dimensional trait. In addition, problems in movement control (the need to allocate attentional capacity) rather than problems in movement speed distinguish children at risk of ADHD from other children. The findings are interpreted as evidence that higher-order executive processes, such as self-control and self-regulation, are already affected early in the development of ADHD.


Measuring 5-year-old Mexican-heritage Children's Ethnic-Racial Identity Attitudes, Centrality, and Knowledge.
Young children are aware of ethnicity-race, yet the field lacks measures to assess ethnic-racial identity (ERI) in early childhood. Thus, the goals of the current study were: (a) to describe three adapted measures that can be used to assess aspects of Mexican-heritage children's ERI (i.e., attitudes, centrality, and knowledge), and (b) to test the psychometric properties of each measure among 182 five-year-old Mexican-heritage children. Results from confirmatory factor analyses supported a 2-factor solution characterizing positive and negative ERI attitudes; the subscales demonstrated adequate reliability and findings provided preliminary support for construct validity. Findings for ERI centrality revealed significant variability among children and initial support for convergent and divergent validity. Support for ERI knowledge was more limited and suggests further development of this measure is needed. Overall, the current study calls attention to the importance of assessing ERI in early childhood, and provides developmentally appropriate assessments to stimulate growth in this area.


Variability in estimated glomerular filtration rate by area under the curve predicts renal outcomes in chronic kidney disease.
Greater variability in renal function is associated with mortality in patients with chronic kidney disease (CKD). However, few studies have demonstrated the predictive value of renal function variability in relation to renal outcomes. This study investigates the predictive ability of different methods of determining estimated glomerular filtration rate (eGFR) variability for progression to renal replacement therapy (RRT) in CKD patients. This was a prospective observational study, which enrolled 1,862 CKD patients. The renal end point was defined as commencement of RRT. The variability in eGFR was measured by the area under the eGFR curve (AUC)%. A significant improvement in model prediction was based on the -2 log likelihood ratio statistic. During a median 28.7-month follow-up, there were 564 (30.3%) patients receiving RRT. In an adjusted Cox model, a smaller initial eGFR AUC%_12M (P < 0.001), a smaller peak eGFR AUC%_12M (P < 0.001), and a larger negative eGFR slope_12M (P < 0.001) were associated with a higher risk of renal end point. Two calculated formulas: initial eGFR AUC%_12M and eGFR slope_12M were the best predictors. Our results demonstrate that the greater eGFR variability by AUC% is associated with the higher risk of progression to RRT.


Pathophysiology of heart failure and frailty: a common inflammatory origin?
Frailty, a clinical syndrome that typically occurs in older adults, implies a reduced ability to tolerate biological stressors. Frailty accompanies many age-related diseases but can also occur without overt evidence of end-organ disease. The condition is associated with circulating inflammatory cytokines and sarcopenia, features that are shared with heart failure (HF). However, the biological underpinnings of frailty remain unclear and the interaction with HF is complex. Here, we describe the inflammatory pathophysiology that is associated with frailty and speculate that the inflammation that occurs with frailty shares common origins with HF. We discuss the limitations in investigating the pathophysiology of frailty due to few relevant experimental models. Leveraging current therapies for advanced HF and current known therapies to address frailty in humans may enable translational studies to better understand the inflammatory interactions between frailty and HF.


K+ (Rb+) transport by a mammary secretory cell apical membrane fraction isolated from goats' milk.
The transport of K+ (Rb+) by cell fragments isolated from goats' milk, which are believed to be pieces of mammary epithelial cell cytoplasm encapsulated by apical membrane, has been studied. K+ (Rb+) accumulation was time dependent and was virtually abolished by 0.1% Triton X-100 which indicates that K+ (Rb+) uptake is into a membrane-limited space rather than by binding. Replacing medium Cl- with SCN- increased whereas gluconate replacement of Cl- decreased K+ (Rb+) influx suggesting that uptake is sensitive to changes in membrane potential. Na+, K+, Li+ and Rb+ ions added to the incubation medium reduced the rate of K+ (Rb+) accumulation. K+ (Rb+) uptake was markedly reduced by both barium ions and quinine; the inhibitory effects were not additive suggesting they are acting at a single locus. Increasing the pH of the medium stimulated the Ba2(+)-sensitive component of K+ (Rb+) influx. The results show that the transport properties of the goats' milk membrane fraction used here are similar to the apical aspect of the intact mammary epithelium. Therefore this membrane preparation may be a good source and model to study mammary secretory cell apical membrane ion transport.


Metabolic response of intestinal microbiota to guar gum consumption.
Guar gum is used extensively as a thickening agent in food, but it remains uncertain whether and to what extent it is fermented by colonic microbiota and whether it has microbiota modulatory properties. To determine the metabolic response of intestinal microbiota to guar gum consumption, specifically, the extent of initial fermentation and subsequent adaptation. Single-center, single arm, open label, proof-of-concept study testing the effect of guar gum on microbiota metabolism and adaptation. Healthy male subjects (n = 12) were administered gum guar (8 g/day) for 18 days. Outcomes were measured before, at initial and late administration: (a) anal gas evacuations (number/day); (b) digestive sensations (daily scales); and (c) fecal gut microbiota taxonomy and metabolic functions by shotgun sequencing. At initial consumption, guar gum induced a transient increase in anal gas evacuations and digestive sensations; gas evacuation completely reverted upon continuous administration, whereas sensations reverted only in part. Guar gum induced moderate changes in human microbiota composition at both taxonomic and functional levels. Positive associations between effects on microbiota (proliferation of Agathobaculum butyriciproducens and Lachnospira pectinoschiza) and hedonic sensations were detected. Guar gum is metabolized by intestinal microbiota, and, upon continuous consumption, induces a selective adaptation of microbial taxonomy and function. These data highlight the potential interest of guar gum for novel prebiotic ingredient formulation.


Effect of the Bone Morphogenetic Protein-2 Doses on the Osteogenic Potential of Human Multipotent Stromal Cells- Containing Tissue Engineered Constructs.
A strategy for improving the efficacy of stem cell-based bone tissue engineering (TE) constructs is to combine bone morphogenetic protein-2 (BMP-2) with multipotent stromal cells (MSC). Previous studies on the potential cooperative effect of BMP-2 with human multipotent stromal cells (hMSCs) on bone formation in vivo have, however, shown contradictory results likely due to the various and/or inappropriate BMP-2 doses. Our results provided evidence that the addition of BMP-2 at low dose only was beneficial to improve the osteogenic potential of hMSCs-containing TE constructs, whereas BMP-2 delivered at high dose overcame the advantage of combining this growth factor with hMSCs. This new knowledge will help in designing improved combination strategies for tissue regeneration with better clinical outcomes.


Evaluation of the POSSUM scoring system for comparative audit in pancreatic surgery.
Wide variations exist in the reported morbidity and mortality rates for major pancreatic resections. The Physiological and Operative Scoring System for enUmeration of Morbidity and mortality (POSSUM) was developed for comparative audit in general surgical patients. It has also been found to be reliable for audit in colorectal, thoracic and vascular surgery with minor modifications. To evaluate POSSUM and its modification for mortality, P-POSSUM, in pancreatic surgery. Retrospective analysis of 50 patients undergoing partial pancreaticoduodenectomy (PD) (46 tumours, 4 chronic pancreatitis) using the POSSUM and P-POSSUM as predictors of morbidity and mortality. These were then compared with the observed values. The POSSUM-predicted mortality was 26%. The P-POSSUM predicted a mortality risk of 6%. The observed mortality was 4%. Using POSSUM for morbidity, the predicted value was 76%. The observed morbidity was 46%. The risk scores for patients with and without morbidity were similar (66.4 +/- 11.0 vs. 68.8 +/- 12.9, p = 0.49). While P-POSSUM appeared satisfactory for predicting mortality risk, POSSUM overestimated morbidity and mortality for PD in a specialist centre. Modifications are needed prior to its application for comparative audit in pancreatic surgery.


Glial cells in familial amyloidotic polyneuropathy.
Transthyretin V30M mutation is the most common variant leading to Familial Amyloidotic Polyneuropathy. In this genetic disorder, Transthyretin accumulates preferentially in the extracellular matrix of peripheral and autonomic nervous systems leading to cell death and dysfunction. Thus, knowledge regarding important biological systems for Transthyretin clearance might unravel novel insights into Familial Amyloidotic Polyneuropathy pathophysiology. Herein, our aim was to evaluate the ability of glial cells from peripheral and autonomic nervous systems in Transthyretin uptake and degradation. We assessed the role of glial cells in Familial Amyloidotic Polyneuropathy pathogenesis with real-time polymerase chain reaction, immunohistochemistry, interference RNA and confocal microscopy. Histological examination revealed that Schwann cells and satellite cells, from an Familial Amyloidotic Polyneuropathy mouse model, internalize and degrade non-fibrillar Transthyretin. Immunohistochemical studies of human nerve biopsies from V30M patients and disease controls showed intracellular Transthyretin immunoreactivity in Schwann cells, corroborating animal data. Additionally, we found Transthyretin expression in colon of this Familial Amyloidotic Polyneuropathy mouse model, probably being synthesized by satellite cells of the myenteric plexus. Glial cells from the peripheral and autonomic nervous systems are able to internalize Transthyretin. Overall, these findings bring to light the closest relationship between Transthyretin burden and clearance from the nervous system extracellular milieu.


Genomic analysis of primordial dwarfism reveals novel disease genes.
Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis.


Micronutrient Gaps in Three Commercial Weight-Loss Diet Plans.
Weight-loss diets restrict intakes of energy and macronutrients but overlook micronutrient profiles. Commercial diet plans may provide insufficient micronutrients. We analyzed nutrient profiles of three plans and compared their micronutrient sufficiency to Dietary Reference Intakes (DRIs) for male U.S. adults. Hypocaloric vegan (Eat to Live-Vegan, Aggressive Weight Loss; ETL-VAWL), high-animal-protein low-carbohydrate (Fast Metabolism Diet; FMD) and weight maintenance (Eat, Drink and Be Healthy; EDH) diets were evaluated. Seven single-day menus were sampled per diet (n = 21 menus, 7 menus/diet) and analyzed for 20 micronutrients with the online nutrient tracker CRON-O-Meter. Without adjustment for energy intake, the ETL-VAWL diet failed to provide 90% of recommended amounts for B12, B₃, D, E, calcium, selenium and zinc. The FMD diet was low (<90% DRI) in B₁, D, E, calcium, magnesium and potassium. The EDH diet met >90% DRIs for all but vitamin D, calcium and potassium. Several micronutrients remained inadequate after adjustment to 2000 kcal/day: vitamin B12 in ETL-VAWL, calcium in FMD and EDH and vitamin D in all diets. Consistent with previous work, micronutrient deficits are prevalent in weight-loss diet plans. Special attention to micronutrient rich foods is required to reduce risk of micronutrient deficiency in design of commercial diets.


RIC8 is a guanine-nucleotide exchange factor for Galpha subunits that regulates growth and development in Neurospora crassa.
Heterotrimeric (αβγ) G proteins are crucial components of eukaryotic signal transduction pathways. G-protein-coupled receptors (GPCRs) act as guanine nucleotide exchange factors (GEFs) for Gα subunits. Recently, facilitated GDP/GTP exchange by non-GPCR GEFs, such as RIC8, has emerged as an important mechanism for Gα regulation in animals. RIC8 is present in animals and filamentous fungi, such as the model eukaryote Neurospora crassa, but is absent from the genomes of baker's yeast and plants. In Neurospora, deletion of ric8 leads to profound defects in growth and asexual and sexual development, similar to those observed for a mutant lacking the Gα genes gna-1 and gna-3. In addition, constitutively activated alleles of gna-1 and gna-3 rescue many defects of Δric8 mutants. Similar to reports in Drosophila, Neurospora Δric8 strains have greatly reduced levels of G-protein subunits. Effects on cAMP signaling are suggested by low levels of adenylyl cyclase protein in Δric8 mutants and suppression of Δric8 by a mutation in the protein kinase A regulatory subunit. RIC8 acts as a GEF for GNA-1 and GNA-3 in vitro, with the strongest effect on GNA-3. Our results support a role for RIC8 in regulating GNA-1 and GNA-3 in Neurospora.


Computerized management of chronic anticoagulation: three years of experience.
Chronically anticoagulated patients taking the drug Warfarin require time intensive management and followup processes to avoid complications. The "Chronic Anticoagulation Clinic" (CAC) protocol is a set of production rules that help manage, treat, and follow-up such patients. The CAC protocol has been in regular use at Intermountain Healthcare (Salt Lake City, UT, USA) for over three years. The results demonstrate an improvement on the number of patients with anticoagulation levels within the desired target range. The protocol alerts have a high acceptance rate (83.4%) and were able to help patients remember to collect their next coagulation test. The CAC protocol results show that production rules can improve the management of chronically anticoagulated patients. Additional studies are required to verify if this experience can be transferred to other institutions.


[Is amalgam stained dentin a proper substrate for bonding resin composite?].
After the removal of amalgam restorations, black staining of dentin is often observed, which is attributed to the penetration of corrosion products from amalgam. A study was carried out to determine whether this amalgam stained dentin is a proper substrate for bonding resin composites. A literature study and an in vitro study showed that Sn and Zn in particular are found in amalgam stained dentin, and this was the case only in demineralised dentin. In vitro, demineralised dentin acted as porte d'entrÈe for amalgam corrosion products. Bond strength tests with 5 adhesive strategies showed no differences between bond strengths to amalgam stained and to sound dentin, but did show different failure types. A clinical study showed good survival of extensive cusp replacing resin composite restorations. No failures were attributed to inadequate adhesion. It is concluded that staining of dentin by amalgam corrosion products has no negative effect upon bond strength of resin composite. It is suggested that Sn and Zn may have a beneficial effect upon dentin, thus compensating the effects of previous carious attacks, preparation trauma and physico-chemical challenges during clinical lifetime.


Segmented band mechanism for itinerant ferromagnetism.
We introduce a novel mechanism for itinerant ferromagnetism, which is based on a simple two-band model, and, by using numerical and analytical methods, we show that the periodic Anderson model contains this mechanism. We propose that the mechanism, which does not assume an intra-atomic Hund's coupling, is present in both the iron group and some f electron compounds.


Suppressor of cytokine signaling 3 suppresses hepatitis C virus replication in an mTOR-dependent manner.
We and others have observed that hepatic levels of suppressor of cytokine signaling 3 (SOCS3) are significantly higher in persons with chronic hepatitis C, particularly those who are nonresponders to interferon (IFN) treatment, than in healthy individuals. However, the relationship between SOCS3 and hepatitis C virus (HCV) replication remains unclear. Given its putative role, we hypothesized that SOCS3 is permissive for viral replication. We therefore used the OR6 cell line, which harbors a genotype 1b full-length HCV replicon, and the genotype 2a full-length HCV strain JFH1 infection system to analyze the effects of SOCS3 overexpression and short hairpin RNA (shRNA)-mediated knockdown on HCV replication. We further analyzed the role of mTOR in the effects of SOCS3 by treating selected cells with rapamycin. OR6 cells and JFH1-infected Huh7.5.1 cells expressed significantly less SOCS3 than control cells. Furthermore, inhibition of HCV replication with the HCV protease inhibitor BILN 2061 restored SOCS3 protein levels. SOCS3 overexpression in OR6 cells and JFH1-infected Huh7.5.1 cells resulted in significantly lower HCV replication than that in the control cells, despite SOCS3-related inhibition of STAT1 phosphorylation and type I IFN signaling. In contrast, JFH1-infected cells with stable SOCS3 knockdown expressed higher levels of HCV proteins and RNA than did control cells. SOCS3-targeting shRNA also knocked down mTOR and phospho-mTOR. The mTOR inhibitor rapamycin reversed the inhibitory effects of SOCS3. In independent investigations, SOCS3 unexpectedly suppressed HCV replication in an mTOR-dependent manner. These findings suggest that increased SOCS3 levels consistently observed in chronic IFN nonresponders may reflect a compensatory host antiviral response to persistent infection and that manipulation of SOCS3/mTOR may offer benefit against HCV infection.


A comparative study on nosocomial and community-acquired spontaneous bacterial peritonitis in patients with liver cirrhosis at a university hospital.
The serious nature of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and the need for timely effective empirical antibiotic therapy in the context of the global surge of antimicrobial resistance and changing epidemiology necessitate a periodic review of the local epidemiologic features of the disease. The aim of the study is to investigate the differences in bacterial profile and antibiotic resistance between nosocomial and community-acquired SBP in patients with liver cirrhosis to guide empirical antibiotic choices for better outcomes. This cross-sectional study included 95 ascitic cirrhotic patients diagnosed with SBP. According to the setting in which the infection was acquired, the patients were divided into two groups: nosocomial and community-acquired SBP. The bacterial profile and rates of multidrug resistance (MDR) phenotype and the extended-spectrum β-lactamase (ESBL) production among Gram-negative isolates in both groups were compared. Escherichia coli was the most frequently isolated bacteria (60% of all isolates) followed by Klebsiella pneumoniae (11.4%). Gram-positive bacteria were only isolated from nosocomial SBP cases; the most common was Staphylococcus aureus (11.4%) followed by coagulase-negative staphylococci (5.7%). High rates of resistance to third-generation cephalosporins, the first-line empirical treatment of SBP, were detected (76.6-100% in nosocomial isolates and 25-87% in community isolates). Carbapenems, amikacin and gentamycin showed good activity against Gram-negative bacilli in both nosocomial and community-acquired isolates. MDR bacteria, including ESBL-producing Enterobacteriaceae, were significantly associated with nosocomial SBP. The significant increase in MDR phenotype and ESBL production among nosocomial isolates necessitates a change in the initial empirical therapy for nosocomial SBP and carbapenems seem good alternatives.


Tenecteplase Thrombolysis in Posterior Circulation Stroke.
One in five ischaemic strokes affects the posterior circulation. Basilar artery occlusion is a type of posterior circulation stroke associated with a high risk of disability and mortality. Despite its proven efficacy in ischaemic stroke more generally, alteplase only achieves rapid reperfusion in ~4% of basilar artery occlusion patients. Tenecteplase is a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase, which can be administered by intravenous bolus. The single-bolus administration of tenecteplase vs. an hour-long alteplase infusion is a major practical advantage, particularly in "drip and ship" patients with basilar artery occlusion who are being transported between hospitals. Other practical advantages include its reduced cost compared to alteplase. The EXTEND-IA TNK trial demonstrated that tenecteplase led to higher reperfusion rates prior to endovascular therapy (22 vs. 10%, non-inferiority p = 0.002, superiority p = 0.03) and improved functional outcomes (ordinal analysis of the modified Rankin Scale, common odds ratio 1.7, 95% CI 1.0-2.8, p = 0.04) compared with alteplase in large-vessel occlusion ischaemic strokes. We recently demonstrated in observational data that tenecteplase was associated with increased reperfusion rates compared to alteplase prior to endovascular therapy in basilar artery occlusion [26% (n = 5/19) of patients thrombolysed with TNK vs. 7% (n = 6/91) thrombolysed with alteplase (RR 4.0 95% CI 1.3-12; p = 0.02)]. Although randomized controlled trials are needed to confirm these results, tenecteplase can be considered as an alternative to alteplase in patients with basilar artery occlusion, particularly in "drip and ship" patients.


[Significance of the factors of hypoxia and endothelial dysfunction in kidney injury in the presence of obesity].
To define the clinical significance of asymmetric dimethylarginine (ADMA) and that of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism as factors of endothelial dysfunction (ED) in the development of early kidney injury in obese patients. The investigation included 86 patients (64 men and 22 women aged 44 +/- 11 years) with abdominal obesity. Along with physical examination, the authors determined albuminuria, calculated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) formula, estimated insulin resistance markers (fasting plasma insulin and C-peptide concentrations and homeostatic model assessment (HOMA) index), as well as serum ADMA levels by enzyme immunoassay in all the patients. C677T polymorphism in the MTHFR gene was studied by allele-specific polymerase chain reaction and restriction fragment length polymorphism analysis. Kidney injury (chronic kidney disease (CKD)) was diagnosed using the Kidney Disease Outcomes Quality Initiative (KDOQI) criteria. Early vascular remodeling was determined from the increased intima-media thickness (IMT) of the common carotid artery (CCA). CKD was diagnosed in 27(31%) patients. The latter, unlike the patients with CKD, were observed to have more pronounced obesity (body mass index (BMI) 36.8 +/- 8.0 and 32.0 +/- 4.7 kg/m2, respectively (p < 0.001)), waist circumference (119 +/- 18 and 109 +/- 11 cm (p = 0.002)), higher levels of C-peptide (1348 +/- 363 and 1028 +/- 363 pmol/I; p < 0.001), insulin (16.9 +/- 7.3 and 11.7 +/- 5.5 microU/ ml; p < 0.001), and HOMA index (4.3 +/- 1.7 and 2.9 +/- 1.5; p < 0.001). In the patients with Stage IIIa CKD, ADMA concentrations (0.77 +/- 0.19 micromol/l) was higher than in those with Stages I (0.58 +/- 0.11 micromol/l; p = 0.048) and II (0.61 +/- 0.13 micromol/l; p = 0.071). An association between ADMA concentrations, CCA IMT, and estimated GFR was revealed in the patients with CKD. The predictors of an estimated GFR reduction in obesity were elevated serum concentrations of ADMA, uric acid, insulin, and HOMA index. The combination of obstructive sleep apnea syndrome and metabolic syndrome increased the risk of CKD by 2.1-fold (95% confidence interval, 1.06-3.14). Evaluation of the impact of MTHFR gene polymorphism on kidney injury in obesity disclosed that the patients with homozygous carriage of the abnormal T allele of the MTHFR gene had a higher risk for Stages I-IIIa CKD (2.60 with 95% confidence interval, 1.32-3.88), more marked obesity and hyperinsulinemia, and increased serum ADMA concentrations. Insulin resistance and ED hold a central position in the pathogenesis of CKD in obese patients. The mechanisms of the atherosclerotic vascular remodeling associated with elevated serum ADMA concentrations are of paramount importance in the progression of early-stage CKD. The homozygous carriage of the abnormal T allele of the MTHFR gene increases the risk of Stages I-IIIa by more than twice.


Paraneoplastic Pyoderma Gangrenosum Associated with Rectal Adenocarcinoma.
Pyoderma gangrenosum (PG) is a rare chronic neutrophilic dermatosis characterized by painful necrotic ulceration. The most common diseases associated with PG are inflammatory bowel disease, certain rheumatologic and hematologic diseases, and malignancy. Here, we describe the case of a 60-year-old man who presented with pruritic and painful erythematous ulcerative macules and patches on both lower extremities, and was diagnosed with PG based on his clinical and histologic features. His PG became exacerbated despite standard therapy with a high-dose systemic steroid in combination with dapsone and cyclosporine. Systemic evaluation of underlying conditions revealed rectal adenocarcinoma at the rectosigmoid junction (T3N0M0), which was completely removed via Hartmann's procedure followed by adjuvant chemotherapy. Two months after anticancer therapy, his PG was completely healed with hypertrophic scarring. Herein, we present the first case of paraneoplastic PG caused by rectal adenocarcinoma in Korea.


>1 MW peak power single-mode high-brightness passively Q-switched Nd 3+:YAG microchip laser.
A high-brightness diode end-pumped Nd:YAG microchip laser, passively Q-switched by a Cr(4+):YAG saturable absorber (SA), has been developed. The dependences of pulse energy and width were investigated based on theoretical verification to enhance the peak power. As a result, the peak power exceeded 1.2 MW with M(2) = 1.04 and spectrum width Delta lambda < 5.1 pm at a repetition rate of 100 Hz. Brightness of 98 TW/sr x cm(2) was obtained with a supplied average electrical power of 2.3 W. The peak power increased up to 2.1 MW with M(2) = 1.36. Peak power of 1.7 MW was obtained from a 2-cm-diameter x 5-cm-long monolithic laser head.


Attention to local and global levels of hierarchical Navon figures affects rapid scene categorization.
In four experiments, we investigated how attention to local and global levels of hierarchical Navon figures affected the selection of diagnostic spatial scale information used in scene categorization. We explored this issue by asking observers to classify hybrid images (i.e., images that contain low spatial frequency (LSF) content of one image, and high spatial frequency (HSF) content from a second image) immediately following global and local Navon tasks. Hybrid images can be classified according to either their LSF, or HSF content; thus, making them ideal for investigating diagnostic spatial scale preference. Although observers were sensitive to both spatial scales (Experiment 1), they overwhelmingly preferred to classify hybrids based on LSF content (Experiment 2). In Experiment 3, we demonstrated that LSF based hybrid categorization was faster following global Navon tasks, suggesting that LSF processing associated with global Navon tasks primed the selection of LSFs in hybrid images. In Experiment 4, replicating Experiment 3 but suppressing the LSF information in Navon letters by contrast balancing the stimuli examined this hypothesis. Similar to Experiment 3, observers preferred to classify hybrids based on LSF content; however and in contrast, LSF based hybrid categorization was slower following global than local Navon tasks.


Factors affecting magnetic retention of particles in the upper airways: an in vitro and ex vivo study.
This paper presents the results of experiments using an in vitro model and an ex vivo animal model (Rana catesbeiana) to study magnetic particle retention in the conducting airways, specifically the trachea and bronchi. The purpose of these experiments was to determine the significant factors for retention of magnetic particles deposited from an aerosol at the airway surface using a magnetic field. The results indicate that the apparent viscosity of the mucus layer at low shear rates is the most significant obstacle to particle retention. The results also show that particle size and aggregation play major roles in particle retention. The mucus transport rate, unlike the effect of fluid velocity in intravenous applications, did not appear to be a determining factor for particle retention. It was also found that a suitably designed magnetic system, aside from having a high intensity, needs to exert a strong radial field to promote particle aggregation. The findings suggest that one possible approach to magnetic particle retention could be delivery of a mucolytic agent along with the drug particles. This study provides the fundamentals needed for development of a targeted magnetic drug delivery system for inhaled therapeutic aerosol particles.


[Detection of herpes simplex virus antigen with an enzyme immunoassay and direct immunofluorescence].
A total of 464 clinical specimens from patients with extragenital and genital lesions and from the cervix of asymptomatic women were examined for the presence of Herpes-simplex-virus antigen by using a commercially available enzyme immunoassay Kit (ELISA, Dakopatts) and a direct immunofluorescence technique with monoclonal antibodies (Syva-Merck). The detection rate was compared to the isolation rate of the tissue-culture technique. In extragenital lesions the sensitivity of the ELISA technique and immunofluorescence was determined to be 78.9% and 80% and in genital lesions 46.2%. In cervical clinical specimens, the sensitivity of both techniques was determined to be 5.7% and 15.4%. An HSV infection, negative in tissue culture, was diagnosed in 22 and 27 cases, respectively, using ELISA and immunofluorescence. This diagnosis was confirmed in 21 and 22 cases by the other immunological technique. For this reason, it can be assumed that in some cases direct immunological techniques can be more sensitive than the tissue culture technique. With regard to asymptomatic and manifest infections, reliable results are only obtainable in cases of manifest disease with blisters or scabs.


Effect of coexposure to DDT and manganese on freshwater invertebrates: pore water from contaminated rivers and laboratory studies.
An environmental survey of several rivers of the southern Huasteca area of Mexico revealed high concentrations of manganese (Mn) and the presence of DDT in the sediments and pore water. Therefore, acute (48-h) toxicities of Mn and DDT were assessed both independently and as a combination on 24-h-old neonates of Daphnia magna Strauss and Lecane quadridentata Ehrenberg. Daphnia magna showed high sensitivity to both toxicants, whereas L. quadridentata was highly resistant to DDT and less susceptible to Mn. For D. magna, the Mn and DDT coexposure was significantly more toxic than any of the singly tested compounds. When D. magna was exposed to sediment pore water, no association was found between the Mn content in the samples and the observed toxicity. Preliminary particle analysis of pore water showed different compounds of Mn, which apparently were not in bioavailable form.


Role of Post-translational Modification of Silent Mating Type Information Regulator 2 Homolog 1 in Cancer and Other Disorders.
Silent mating type information regulator 2 homolog 1 (SIRT1), an NAD+-dependent histone/protein deacetylase, has multifarious physiological roles in development, metabolic regulation, and stress response. Thus, its abnormal expression or malfunction is implicated in pathogenesis of various diseases. SIRT1 undergoes post-translational modifications, including phosphorylation, oxidation/reduction, carbonylation, nitrosylation, glycosylation, ubiquitination/deubiquitination, SUMOylation etc. which can modulate its catalytic activity, stability, subcellular localization, and also binding affinity for substrate proteins. This short review highlights the regulation of SIRT1 post-translational modifications and their pathophysiologic implications.


TFR2-related haemochromatosis in the Netherlands: a cause of arthralgia in young adulthood.
Type 3 hereditary haemochromatosis (HH) is a rare iron overload disorder caused by variants in the transferrin 2 receptor (TFR2) gene. We aim to present characteristics of patients diagnosed with TFR2-HH in the Netherlands, in order to increase knowledge and awareness of this disease. We collected clinical, biochemical and genetic data from four patients from three families diagnosed with HH type 3 in the Netherlands between 2009 and 2016. Three women and one man diagnosed with HH type 3 presented with arthralgia and elevated ferritin levels and transferrin saturation (TSAT) at ages 25-41 years. The hepcidin/ferritin ratio as measured in three patients was low. Liver iron content in two patients as assessed by MRI or liver biopsy was highly increased (250 and 362.7 μmol iron/g dry weight, respectively, reference < 35 μmol/g). DNA analysis revealed four different TFR2 pathogenic variants: one nonsense, one splicing and two missense variants, of which three are novel. Phlebotomy decreased the serum iron parameters but did not relieve the arthralgia. In patients with a combination of elevated TSAT and ferritin in the absence of anaemia, and after exclusion of HFE-related HH, rare forms of HH should be considered. In these cases, presentation with arthralgia in young adulthood, low hepcidin/ferritin ratio and/or liver iron content > 100 μmol/g form an indication for analysis of the TFR2 gene. Although type 3 HH is extremely rare, awareness of the disease among physicians is important in order to achieve an early diagnosis and prevent complications, such as liver damage.


Nurse practitioners and GPs--addressing the needs of older persons living in residential aged care.
The Australian population is becoming progressively older, placing significant pressure on both the supply of supported accommodation and health services. Collaboration between general practitioners and nurse practitioners over the care of people living in residential aged care facilities has the potential to promote continuity of care, decrease hospitalisations and readmissions, enhance patient satisfaction, reduce costs, enhance working relations between medicine and nursing, and improve residents' access to care. It will require improved communication and the overcoming of several attitudinal and organisational barriers.


Calcium antagonists and hormone release. VI. Effects of a calcium antagonist (verapamil) on the biphasic insulin release in vivo.
The present study was designed to investigate the influence of a calcium antagonist (verapamil) on the two phases of insulin release. The present results confirmed our previous studies and in vitro data, showing that the first phase insulin release is not inhibited by a calcium antagonist and strongly indicated that glucose stimulated insulin secretion has two phases of release: (1) the first phase of release, which is independent from extracellular calcium; (2) the second phase of release, which was inhibited by calcium antagonists, is dependent from calcium uptake from an extracellular source.