[Gallbladder torsion: a case report and review of the literature].
Gallbladder torsion is a rare but potentially life-threatening event due to its insidious course and to the gravity of the clinical picture when the diagnosis is established late. In 85% of cases this situation affects females, aged 70 to 90 years. The aetiopathogenesis is still unknown and the diagnosis is often made during surgery. A thorough review of the literature suggests a specific clinical pattern which, when combined with improvements in radiological techniques, should allow early diagnosis and treatment. Nevertheless, only 10% of cases are correctly diagnosed before surgery. The aim of this case report was to evaluate the specific pattern of this clinical picture and the accuracy of the radiological and laboratory findings for the purposes of achieving an early diagnosis and adequate treatment.


Chromatographic and electrophoretic methods for Lingzhi pharmacologically active components.
Lingzhi is the Chinese name given to the Ganoderma family of mushrooms, which was considered the most valuable medicine in ancient China and was believed to bring longevity, due to its mysterious power of healing the body and calming the mind. Today, Lingzhi is still widely revered as a valuable health supplement and herbal medicine worldwide, as studies (mostly conducted in China, Korea, Japan and the United States) into the medicinal and nutritional values of Lingzhi revealed that it does indeed contain certain bioactive ingredients (such as triterpenes and polysaccharides) that might be beneficial for the prevention and treatment of a variety of ailments, including important diseases such as hypertension, diabetes, hepatitis, cancers, and AIDS. As research into the biological activities of Lingzhi, as well as the quality assurance and quality control of Lingzhi products, require the isolation/purification of active ingredients from Lingzhi, followed by subsequent analytical and/or preparative separations, the present review summarizes the various chromatographic and electrophoretic methods (as well as sample pretreatment methods) typically employed to achieve such extraction/separation procedures.


Emotion, motivation, and text comprehension: the detection of contradictions in passages.
The authors investigated the effects of experimentally induced mood states on the identification of contradictions in text passages and ratings of comprehension in 3 experiments. Mood impaired comprehension in college students across a variety of passages, as evidenced by a depressive impairment in contradiction identification and an increased number of false identifications among depressed participants. Additionally, depressed individuals were less accurate in their judgments of passage difficulty. These findings are consistent with the resource allocation model of mood effects, which attributes impaired comprehension to the activation of intrusive, irrelevant thoughts during reading of the passage. It is further argued that these results cannot be explained simply by a deficit in motivation of the depressed participants.


CRISPR/Cas9-based functional characterization of the pigmentation gene ebony in Plutella xylostella.
Body pigmentation is an important character of insects in adapting to biotic and abiotic environmental challenges. Additionally, based on the relative ease of screening, several genes involved in insect melanization have been used in classic genetic studies or as visual markers in constructing transgenic insects. Here, a homologue of the Bombyx mori melanization-inhibiting gene ebony, associated with the conversion of dopamine to N-β-alanyl dopamine, was identified in a global pest, Plutella xylostella. The CRISPR/Cas9 system was applied to generate multiple Pxebony knockout alleles which were crossed to produce a Pxebony knockout strain, showing darker pigmentation in larvae, pupae and adults, compared with wildtype. Interestingly, we observed that Pxebony heterozygotes displayed an intermediate darkened phenotype, indicating partial dominance between the knockout and wildtype alleles. The fitness costs of Pxebony deficiency were also assessed in the mutant strain, indicating that embryo hatchability and larval survival were significantly reduced, while the eclosion rate was not obviously affected. Our work provides a potential target for exploring CRISPR-based genetics-control systems in this economically important pest lepidopteran.


Nitrogen metabolism and nitrogen control in corynebacteria: variations of a common theme.
The published genome sequences of Corynebacterium diphtheriae, Corynebacterium efficiens, Corynebacterium glutamicum and Corynebacterium jeikeium were screened for genes encoding central components of nitrogen source uptake, nitrogen assimilation and nitrogen control systems. Interestingly, the soil-living species C. efficiens and C. glutamicum exhibit a broader spectrum of genes for nitrogen transport and metabolism than the pathogenic species C. diphtheriae and C. jeikeium. The latter are characterized by gene decay and loss of functions like urea metabolism and nitrogen-dependent transcription control. The global regulator of nitrogen regulation AmtR and its DNA-binding motif are conserved in C. diphtheriae, C. efficiens and C. glutamicum, while in C. jeikeium, an AmtR-encoding gene as well as putative AmtR-binding motifs are missing.


Surgical treatment of hepatocellular carcinoma.
The incidence of hepatocellular carcinoma (HCC) in Europe and throughout the world is currently increasing. This is caused by an increase in the number of patients with alcoholic liver damage, metabolic syndrome, and by increasing incidence of hepatitis B and C.From January 1, 2004 to December 31, 2013, resection or radiofrequency ablation of the liver was done in 360 patients with benign lesions or malignant tumors of the liver. In 28 patients HCC was diagnosed and histologically confirmed (7.8 %). Seven patients had HCC associated with liver cirrhosis (25 %), and 21 patients were without histologically confirmed cirrhosis (75 %). R0 resection was done in 18 (64 %) patients.Surgical complications occurred in 6 (21 %) patients and reoperation due to tumor relapse or progression was done eight times in 6 (21 %) patients. One-year and five-year patients' survivals were 64 % and 10 %, repectively, and did not statistically differ from the survival of the whole set of patients with tumor diseases in the given time period. In the future it will be possible to improve the long-term survival of patients with HCC by using screening methods for presymptomatic diagnosis of HCC, precise preoperative diagnosis and efforts for R0 resection (Tab. 1, Fig. 4, Ref. 11).


siRNA targeting TCTP suppresses osteosarcoma cell growth and induces apoptosis in vitro and in vivo.
Osteosarcoma (OS) remains the most frequent primary malignant bone tumor in adolescents. However, the molecular cause of the disease is poorly elucidated. In the present study, we primarily found that translationally controlled tumor protein (TCTP) was overexpressed in human OS tissues and cell lines. To investigate the function of TCTP in OS cell growth, an RNA interference lentivirus system was employed to deplete TCTP expression in Saos-2 and U2OS cell lines. Specific knockdown of TCTP significantly impaired cell proliferation and colony-formation capacity in both OS cell lines. Moreover, depletion of TCTP caused a significant accumulation of OS cells in the S phase and eventually induced cell apoptosis. Expression levels of the G2/M phase regulators cyclin B1 and Cdc25A were decreased, and apoptotic markers Bad and caspase-3 were increased in both OS cell lines after depletion of TCTP. Furthermore, depletion of TCTP potently inhibited the growth of xenografts in nude mice. Our results indicate that inhibition of TCTP expression exerts potential antitumor activity and may be a novel therapeutic approach in human OS.


Molecular insights into the role of white adipose tissue in metabolically unhealthy normal weight and metabolically healthy obese individuals.
Obesity is a risk factor for the development of type 2 diabetes and cardiovascular disease. However, it is now recognized that a subset of individuals have reduced cardiometabolic risk despite being obese. Paradoxically, a subset of lean individuals is reported to have high risk for cardiometabolic complications. These distinct subgroups of individuals are referred to as metabolically unhealthy normal weight (MUNW) and metabolically healthy obese (MHO). Although the clinical relevance of these subgroups remains debated, evidence shows a critical role for white adipose tissue (WAT) function in the development of these phenotypes. The goal of this review is to provide an overview of our current state of knowledge regarding the molecular and metabolic characteristics of WAT associated with MUNW and MHO. In particular, we discuss the link between different WAT depots, immune cell infiltration, and adipokine production with MUNW and MHO. Furthermore, we also highlight recent molecular insights made with genomic technologies showing that processes such as oxidative phosphorylation, branched-chain amino acid catabolism, and fatty acid β-oxidation differ between these phenotypes. This review provides evidence that WAT function is closely linked with cardiometabolic risk independent of obesity and thus contributes to the development of MUNW and MHO.


Influence of teicoplanin on the chemiluminescence of phagocytosing human granulocytes.
Teicoplanin is a new glycopeptide antibiotic that is structurally related to vancomycin. It is especially active against virtually all gram positive bacteria including methicillin-resistant staphylococci. The aim of this study was to evaluate the influence of teicoplanin on the phagocytosis of human neutrophils, using the chemiluminescence reaction method. We incubated three different concentrations (2, 5, 10 microg/ml) of teicoplanin for one and three hours with polymorphonuclear leukocytes of healthy human volunteers and then measured the chemiluminescence reaction during zymosan phagocytosis. The neutrophil function was not influenced by teicoplanin.


HLA genotype of patients with severe haemophilia A due to intron 22 inversion with and without inhibitors of factor VIII.
Molecular genetic studies have shown that development of antibodies to factor VIII (inhibitors) occurs most frequently in patients with severe haemophilia due to major gene lesions including inversions, stop codons and large deletions. Previous studies of HLA type were performed on inhibitor and non-inhibitor patients with diverse uncharacterized mutations which may have confounded detection of significant associations. We therefore selected a group of patients with a single mutation type, the prevalent intron 22 inversion, with or without inhibitors, to determine HLA genotype. Seventy-one such patients, 42 without and 29 with inhibitors (13 high, 9 low and 7 transient responders) were genotyped for MHC Class I HLA-A, -B, -C and Class II HLA-DQA, -DQB and -DRB loci. No strong correlation of any HLA-allele to inhibitor or non-inhibitor status was found. However, alleles of the haplotype HLA-A3, HLA-B7, HLA-C7, HLA-DQA0102, HLA-DQB0602, HLA-DR15 occurred more often in inhibitor patients. Since the alleles of this extended haplotype are common in the North European population only a very strong association would achieve statistical significance. Further studies of groups of patients similar to those studied here will be needed to confirm or exclude this association.


ANKLE JOINT CONTROL DURING SINGLE-LEGGED BALANCE USING COMMON BALANCE TRAINING DEVICES - IMPLICATIONS FOR REHABILITATION STRATEGIES.
A lateral ankle sprain is the most prevalent musculoskeletal injury in sports. Exercises that aim to improve balance are a standard part of the ankle rehabilitation process. In an optimal progression model for ankle rehabilitation and prevention of future ankle sprains, it is important to characterize different balance exercises based on level of difficulty and sensori-motor training stimulus. The purpose of this study was to investigate frontal-plane ankle kinematics and associated peroneal muscle activity during single-legged balance on stable surface (floor) and three commonly used balance devices (Airex®, BOSU® Ball and wobble board). Descriptive exploratory laboratory study. Nineteen healthy subjects performed single-legged balance with eyes open on an Airex® mat, BOSU® Ball, wobble board, and floor (reference condition). Ankle kinematics were measured using reflective markers and 3-dimensional recordings and expressed as inversion-eversion range of motion variability, peak velocity of inversion and number of inversion-eversion direction changes. Peroneus longus EMG activity was averaged and normalized to maximal activity during maximum voluntary contraction (MVC), and in addition amplitude probability distribution function (APDF) between 90 and 10% was calculated as a measure of muscle activation variability. Balancing on BOSU® Ball and wobble board generally resulted in increased ankle kinematic and muscle activity variables, compared to the other surfaces. BOSU® Ball was the most challenging in terms of inversion-eversion variability while wobble board was associated with a higher number of inversion-eversion direction changes. No differences in average muscle activation level were found between these two surfaces, but the BOSU® Ball did show a more variable activation pattern in terms of APDF. The results showed large kinematic variability among different balance training devices and these differences are also reflected in muscle activation variability. The two most challenging devices were BOSU® Ball and Wobble board compared to Airex® and floor. This study can serve as guidance for clinicians who wish to implement a gradual progression of ankle rehabilitation and prevention exercises by taking the related ankle kinematics and muscle activity into account. Level 3.


Bradycardia and hypotension in a patient with severe aortic stenosis receiving electroconvulsive therapy dose titration for treatment of depression.
Aortic stenosis (AS) is a risk factor for increased morbidity and mortality in patients undergoing procedures requiring general anesthesia. The absolute risk to patients with AS receiving electroconvulsive therapy (ECT) is unknown, but given the physiologic changes occurring in AS, it is reasonable to postulate that such patients are at increased risk for untoward events. In this article, we present the case of a 75-year-old woman with severe AS who developed hypotension and bradycardia during ECT dose titration. We discuss practical considerations and risk reduction strategies when using ECT in patients with severe AS.


Personality Characteristics as Predictive Factors for the Occurrence of Depressive Disorder.
The depressive disorder is one of the most frequent mental disorders, which is often associated with severe dysfunctionality. Personality traits are considered as important factors for the occurrence of depressive disorder. To determine the specificity of personality dimensions as predictive factors of depressive disorder. This research was conducted at the University Psychiatric Clinic Skopje as a "case-control" study. TCI-R (temperament and character inventory - revised) was used as the main research instrument. There are specific personality traits expressed through high scores of Harm Avoidance and low scores of Self -Directedness traits as predictive factors related to an incidence of the depressive disorder. The results of this study show that certain personal traits, and more specific HA and SD, are with a specific predictability of the depressive disorder.


Prevalence of Yersinia enterocolitica in market weight hogs in the United States.
Pigs are the major animal reservoir for Yersinia enterocolitica strains, which are potentially pathogenic for humans. The goals of this study were (i) to estimate the individual animal and on-farm prevalences of Y. enterocolitica in hogs based on tonsil samples collected during National Animal Health Monitoring System Swine 2002 study and (ii) to use these data with data previously published for fecal samples to determine on-farm risk factors for Y. enterocolitica. Tonsil swabs (1,218) and fecal samples (2,847) were collected on 124 farms located in the top 17 pork-producing states. Ten percent of tonsils (122 of 1,218 samples) were positive in irgasan-tiracillin-chlorate (ITC) enrichment broth by real-time PCR, but only 5.6% of samples (68 of 1,218) were positive after subculture on the more selective cefsulodin-irgasan-novobiocin (CIN) agar. For tonsils, the on-farm prevalence based on real-time PCR detection of the ail gene in ITC enrichment broth cultures was 32% (32 of 100 premises sampled); the prevalence based on subculture in CIN agar was 19.6% (20 of 102 premises). Results of bacteriological isolation and real-time PCR analysis of tonsils and feces were combined to estimate prevalence (individual animal and farm), which was subsequently correlated with 40 farm management practices. Four factors and their accompanying odds ratios (ORs) were identified in the final regression model: location in a central state (OR = 0.3), vaccination for Escherichia coli (OR = 3.0), percentage of deaths due to scours (OR = 3.5), and presence of meat or bone meal in grower-finisher diet (OR = 4.1).


Review of fungus-feeding urothripine species from China, with descriptions of two new species (Thysanoptera:Phlaeothripidae).
Twelve species of urothripine Phlaeothripidae are recorded from China, including two new species that are described and illustrated here, Stephanothrips austrinus sp. n. and Urothrips calvus sp. n. A new key is provided to the urothripine species known from China together with new collection data.


Preliminary observations on the use of the latex agglutination test for detecting circulating trypanosomal antibodies in game animals in the Lambwe Valley.
The first use of the latex agglutination test (LAT) for determining the frequency of circulating trypanosomal antibodies in a sample of game animals collected in the Lambwe Valley, Kenya, is described. The immunological examination of animals belonging to 9 species revealed an incidence of circulating antibody of 25.5%, which was only slightly higher than, and therefore in close agreement with, the results of a concurrent parasitological survey. It is concluded that the LAT is very suitable for determining the overall incidence of trypanosomal infections in wildlife communities.


An unprecedented trinuclear structure involving two high-spin and one spin-crossover iron(II) centers.
Anaerobic reaction of ferrous thiocyanate with the deprotonated form of the pentadentate dinucleating Schiff base 1,3-bis[(2-pyridylmethyl)imino]propan-2-ol (LH) yields the novel trinuclear [Fe3L2(NCS)4(H2O)] species 1. LH results from the bis-condensation of 2-acetyl-pyridine with 1,3-diaminopropan-2-ol and includes an N4O donor set. The X-ray crystal structure of 1 [C38H40N12O3S4Fe3, triclinic, space group P-1; a = 10.7730(10) angstroms, b = 12.2048(14) angstroms, c = 19.0559(19) angstroms, alpha = 76.908(12) degrees, beta = 89.106(12) degrees, gamma = 79.637(12) degrees, V = 2399.8(4) angstroms3] can be described either as a bent linear arrangement of ferrous centers pairwise bridged through the alkoxo oxygen atom of L- or as a triangular FeII3 core with an Fe2-SCN-Fe3 bridge as the longer side of the Fe1-Fe2-Fe3 triangle. The metric parameters characterizing the ligand environments of the three ferrous centers in 1 and its Mössbauer spectra show that this unprecedented trinuclear structure involves two high-spin (Fe2 and Fe3) and one spin-crossover (Fe1) FeII centers. The donor set to the spin-crossover center (Fe1) is unprecedented: two Npyridine, two Nimine, and two Oalkoxo. Weak antiferromagnetic interactions transmitted through the end-to-end NCS bridge and/or through the O1-Fe1-O2 bridge operate between Fe2 and Fe3.


Growth rate, carcass characteristics and meat quality of growing lambs fed buckwheat or maize silage.
This study evaluated inclusion of buckwheat silage to the diet of growing lambs in terms of meat quality as compared to maize silage. Buckwheat, rich in total phenols (TP, 33 g/kg dry matter [DM]), was harvested at the end of the milk stage and ensiled in 40 kg plastic bags after wilting (294 g/kg silage DM). A total of 18 growing lambs (21.6±1.2) were individually fed isonitrogenous and isoenergetic total mixed rations (TMR) for 75 d that either contained buckwheat or maize silage at DM proportions of 0.50. At the end of feeding trail all lambs were slaughtered to assess carcass characteristics and meat quality. Buckwheat silage increased (p<0.01) the DM intake of lambs as compared to maize silage, but had no effects (p>0.05) on live weight gain and feed efficiency. Carcass weight, dressing percentage, meat pH, water holding capacity, cooking loss, shear force (kg/cm2), and total viable bacteria count of meat did not differ (p>0.05) between the treatments. However, TP content of meat increased (p<0.001) by feeding buckwheat TMR. Feeding buckwheat TMR also decreased (p<0.05) the b* values of meat. The results provide that buckwheat silage is palatable and could successfully include TMR of growing lambs with no adverse effects on performance, carcass and meat quality. Additionally, feeding buckwheat silage to lambs offers increased TP in meat.


Inhibition of gene expression by peptide nucleic acids in cultured cells.
We have tested in cultured cells the capacity of antisense and antigene PNAs to inhibit, in a sequence specific manner, the expression of oncogenes in leukaemia and pancreatic carcinoma cells. The results observed appeared promising and suggest that PNA may play in the future an important role in targeting disease-related genes.


The effect of unilateral nephrectomy on the activity of ribosomes in the remaining kidney.
1. Ribosomes isolated from hypertrophic kidneys were examined at different time intervals after unilateral nephrectomy. The activity of ribosomes measured by [14C] leucine incorporation and synthesis of polyphenylalanine from [14C]Phe-tRNA, was increased after 24 h, whereas changes in the composition of ribosomal protein fractions appeared as early as within 6 hours after the operation. 2. In hypertrophic kidney the content of ribosomes increased but the ratio of free and membrane-bound ribosomes remained practically unaltered. However, the specific activity of free ribosomes was twice as high as that of bound ribosomes. 3. It is concluded that the enhanced activity of free ribosomes is one of the factors responsible for the increased protein synthesis in hypertrophic kidney.


Peribysins A-D, potent cell-adhesion inhibitors from a sea hare-derived culture of Periconia species.
Peribysins A-D 1-4, including a new type of furanofuran, have been isolated from a strain of Periconia byssoides originally separated from the sea hare Aplysia kurodai, and their relative stereostructures have been elucidated on the basis of NMR spectral analyses. All these metabolites potently inhibited the adhesion of human-leukemia HL-60 cells to HUVEC. The activity of compound 4, exhibiting the most potent inhibitory activity, was 380 times as potent as herbimycin A (standard).


Therapeutic Intervention of Serine Protease Inhibitors against Hepatitis C Virus.
Hepatitis C virus (HCV) is a globally prevalent and hazardous disorder that is responsible for inducing several persistent and potentially fatal liver diseases. Current treatment strategies offer limited efficacy, often accompanied by severe and debilitating adverse effects. Consequently, there is an urgent and compelling need to develop novel therapeutic interventions that can provide maximum efficacy in combating HCV while minimizing the burden of adverse effects on patients. One promising target against HCV is the NS3-4A serine protease, a complex composed of two HCV-encoded proteins. This non-covalent heterodimer is crucial in the viral life cycle and has become a primary focus for therapeutic interventions. Although peginterferon, combined with ribavirin, is commonly employed for HCV treatment, its efficacy is hampered by significant adverse effects that can profoundly impact patients' quality of life. In recent years, the development of direct-acting antiviral agents (DAAs) has emerged as a breakthrough in HCV therapy. These agents exhibit remarkable potency against the virus and have demonstrated fewer adverse effects when combined with other DAAs. However, it is important to note that there is a potential for developing resistance to DAAs due to alterations in the amino acid position of the NS3-4A protease. This emphasizes the need for ongoing research to identify strategies that can minimize the emergence of resistance and ensure long-term effectiveness. While the combination of DAAs holds promise for HCV treatment, it is crucial to consider the possibility of drug-drug interactions. These interactions may occur when different DAAs are used concurrently, potentially compromising their therapeutic efficacy. Therefore, carefully evaluating and monitoring potential drug interactions are vital to optimize treatment outcomes. In the pursuit of novel therapeutic interventions for HCV, the field of computational biology and bioinformatics has emerged as a valuable tool. These advanced technologies and methodologies enable the development and design of new drugs and therapeutic agents that exhibit maximum efficacy, reduced risk of resistance, and minimal adverse effects. By leveraging computational approaches, researchers can efficiently screen and optimize potential candidates, accelerating the discovery and development of highly effective treatments for HCV, treatments.


Speed and Diffusion of Kinesin-2 Are Competing Limiting Factors in Flagellar Length-Control Model.
Flagellar length control in Chlamydomonas is a tractable model system for studying the general question of organelle size regulation. We have previously proposed that the diffusive return of the kinesin motor that powers intraflagellar transport can play a key role in length regulation. Here, we explore how the motor speed and diffusion coefficient for the return of kinesin-2 affect flagellar growth kinetics. We find that the system can exist in two distinct regimes, one dominated by motor speed and one by diffusion coefficient. Depending on length, a flagellum can switch between these regimes. Our results indicate that mutations can affect the length in distinct ways. We discuss our theory's implication for flagellar growth influenced by beating and provide possible explanations for the experimental observation that a beating flagellum is usually longer than its immotile mutant. These results demonstrate how our simple model can suggest explanations for mutant phenotypes.


In vivo Neuroprotective Effect of a Self-assembled Peptide Hydrogel.
Traumatic brain injury (TBI) is associated with poor intrinsic healing responses and long-term cognitive decline. A major pathological outcome of TBI is acute glutamate-mediated excitotoxicity (GME) experienced by neurons. Short peptides based on the neuroprotective extracellular glycoprotein ependymin have shown the ability to slow down the effect of GME - however, such short peptides tend to diffuse away from target sites after in vivo delivery. We have designed a self-assembling peptide containing an ependymin mimic that can form nanofibrous matrices. The peptide was evaluated in situ to assess neuroprotective utility after an acute fluidpercussion injury. This biomimetic matrix can conform to the intracranial damaged site after delivery, due its shear-responsive rheological properties. We demonstrated the potential efficacy of the peptide for supporting neuronal survival in vitro and in vivo. Our study demonstrates the potential of these implantable acellular hydrogels for managing the acute (up to 7 days) pathophysiological sequelae after traumatic brain injury. Further work is needed to evaluate less invasive administrative routes and long-term functional and behavioral improvements after injury.


Oxidative stress in cardiovascular disease.
Over the last two decades, it has become increasingly clear that reactive oxygen species (ROS), including free radicals are involved in cardiovascular disease. In recent years, there has been a growing interest in the clinical implications of these oxidants. The ROS are common by-products of many oxidative biochemical and physiological processes. They can be released by xanthine oxidase, NAD(P)H oxidase, lipoxygenases, mitochondria, or the uncoupling of nitric oxide synthase in vascular cells. ROS mediate various signaling pathways that underlie vascular inflammation in atherogenesis. Various animal models of oxidative stress support that ROS have causal role in atherosclerosis and other cardiovascular diseases. They are too reactive to be tolerated in living tissue, and aerobic organisms use sophisticated defense system, both enzymatic and non-enzymatic for prevention of overload of free radicals. In a number of pathophysiological conditions, the delicate equilibrium between free-radical production and antioxidant capability can be altered in favor of the former, thus leading to oxidative stress and increased tissue injury. This review focuses on the biochemical evidences concerning involvement of ROS in several cardiovascular diseases, namely atherosclerosis, heart failure, hypertension and ischemia/reperfusion injury.


Implicit and explicit measures of alcohol and smoking cognitions.
The present study tested convergent, discriminant, and incremental validity of implicit and explicit measures of alcohol and smoking cognitions. College-aged participants (n = 264) completed questionnaire measures of alcohol and smoking expectancies and behavior. Participants also completed the Implicit Association Test (IAT; Greenwald, McGhee, & Schwartz, 1998) for alcohol and smoking on two occasions, approximately 1 month apart. Psychometric qualities of these IATs were evaluated. Modest associations were found between implicit and explicit measures for the same substance. Both implicit and explicit measures had unique associations with use. Discriminant validity was stronger for alcohol measures than for smoking measures. These results support the utility of the IAT as a technique for assessing implicit associations about alcohol and smoking. They also provide some evidence that smoking motivations may make unique contributions to alcohol use.


Pharmacokinetics and metabolism of 14C-brivaracetam, a novel SV2A ligand, in healthy subjects.
This study was designed to investigate the human absorption, disposition, and mass balance of (14)C-brivaracetam, a novel high affinity SV2A ligand with potent anticonvulsant activity. Six healthy male subjects received a single p.o. dose of (14)C-brivaracetam (150 mg, 82 microCi, or 3.03 MBq). Serial blood and complete urine and feces were collected until 144 h postdose. Expired air samples were obtained until 24 h. Brivaracetam was rapidly absorbed, with C(max) of 4 mug/ml occurring within 1.5 h of dosing. Unchanged brivaracetam amounted to 90% of the total plasma radioactivity, suggesting a modest first-pass effect. Plasma protein binding of radioactivity was low (17.5%). Urinary excretion exceeded 90% after 2 days, and the final mass balance reached 96.8% of the radioactivity in urine and 0.7% in feces. Only 8.6% of the radioactive dose was recovered in urine as unchanged brivaracetam, the remainder being identified as non-cytochrome P450 (P450)- and P450-dependent biotransformation products resulting from hydrolysis of the amide moiety (M9, 34.2%), hydroxylation of the n-propyl side chain (M1b, 15.9%), and a combination of these two pathways leading to the hydroxy acid (M4b, 15.2%). Minor amounts of taurine and glucuronic acid conjugates and other oxidized derivatives were also identified. Brivaracetam is completely absorbed, is weakly bound to plasma proteins, extensively biotransformed through several metabolic pathways, and eliminated renally.


Stable and oxidative charged Ru enhance the acidic oxygen evolution reaction activity in two-dimensional ruthenium-iridium oxide.
The oxygen evolution reactions in acid play an important role in multiple energy storage devices. The practical promising Ru-Ir based catalysts need both the stable high oxidation state of the Ru centers and the high stability of these Ru species. Here, we report stable and oxidative charged Ru in two-dimensional ruthenium-iridium oxide enhances the activity. The Ru0.5Ir0.5O2 catalyst shows high activity in acid with a low overpotential of 151 mV at 10 mA cm-2, a high turnover frequency of 6.84 s-1 at 1.44 V versus reversible hydrogen electrode and good stability (618.3 h operation). Ru0.5Ir0.5O2 catalysts can form more Ru active sites with high oxidation states at lower applied voltages after Ir incorporation, which is confirmed by the pulse voltage induced current method. Also, The X-ray absorption spectroscopy data shows that the Ru-O-Ir local structure in two-dimensional Ru0.5Ir0.5O2 solid solution improved the stability of these Ru centers.


Alexander's disease with Rosenthal fibre formation in an adult.
The case of a woman who had a mild mental and physical handicap all her life is described. At the age of 39 years she began a progressive deterioration which terminated with her death after a year. CT scanning revealed basal ganglia calcification and at necropsy there was evidence of widespread generalised myelin loss with extensive Rosenthal fibre formation. The hypothesis that this may be an adult form of Alexander's disease is discussed.


CGA gene (coding for the alpha subunit of glycoprotein hormones) overexpression in ER alpha-positive prostate tumors.
The precise role of estrogen, estrogen receptor (ER) and ER-responsive genes in prostate carcinogenesis is unclear. Paradoxically, estrogens and antiestrogens are used in the treatment of advanced metastatic prostate cancers. Recently, we identified CGA gene coding for the alpha subunit of glycoprotein hormones as a new ER alpha-responsive gene in human breast cancer cells. The aim of this study was to explore the role of CGA in the second major hormone-related cancer, i.e. prostate cancer. We quantified CGA mRNA in nine cases of benign prostatic hyperplasia (BPH) and 23 sporadic prostate tumors (TP) by using a real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. CGA overexpression (> 10 S.D. above the mean in normal prostate tissues (NP)) was observed in 39% of the TP (ranging from 4.4 to 174.5 times the level in NP) and in none of the BPH samples. CGA overexpression was not accompanied by overexpression of the CGB, LHB, TSHB or FSHB genes to produce ectopic glycoprotein hormones. CGA gene overexpression correlated with ER alpha normal expression (P = 0.016), but not with ER beta or androgen receptor (AR) expression status. These results point to CGA gene as a member of a novel dysregulated pathway in prostate cancer. CGA should therefore be considered for investigation as possible novel molecular marker in clinical applications and as possible new potential therapeutic target.


Dual functioning microspheres embedded crosslinked gelatin cryogels for therapeutic intervention in osteomyelitis and associated bone loss.
In the present research,we simultaneously addressed the condition of osteomyelitis and osteoporosis by developing a gelatin based chemically cross linked cryogel system embedded with CaCO3 microspheres and ciprofloxacin hydrochloride was incorporated in both the microspheres and the 3D matrix of cryogel. The fabricated cryogel was characterized for the swelling ratio, swelling kinetics, porosity, pore volume, compression strength and in vitro rate of degradation which were found to be dependent on the concentration of gelatin, duration of freezing and number of freeze-thaw cycles. The sustained release of drug was obtained up to 21days after the initial burst, and the concentration was maintained above the MIC for the entire duration of the study. The in vitro antibacterial study in Staphylococcus aureus and Escherichia coli exhibited 33mm, 30mm, 28mm, 27mm and 43mm, 37mm, 37mm, and 36mm zone of inhibition respectively at day 1, 3, 5 and 7. The cell viability, number of cells in the growth phase and alkaline phosphatase levels were found to be significantly higher in rat osteoblasts cultured in cryogel as compared to 2D surface. All these results demonstrate the propitious potential of this microsphere incorporated, ciprofloxacin-loaded, industrially scalable cryogel system for therapeutic intervention in osteoporosis and associated osteomyelitis.


The impact of nutrition in cystic fibrosis: a review.
A high energy intake, compensating for malabsorption, and the energy cost of lung disease, lung infections, and the underlying metabolic abnormality, is required to ensure normal growth in patients with cystic fibrosis. This goal can be readily achieved by adherence to a high quantity, normally balanced diet (with 40% of the energy as triglycerides of long-chain fatty acids). In contrast, this goal cannot be reached in the majority of patients adhering to low-fat and thus low-energy-containing diets, which almost inevitably lead to malnutrition with wasting and stunting. The prevention of malnutrition may well have considerably enhanced the prognosis of patients at one clinic. Further work is needed to define the interrelationship of nutrition and lung disease, and to define the appropriate nutrient requirements induced by the lung disease per se, recurrent infections, and the underlying disease process.


NGR-peptide-drug conjugates with dual targeting properties.
Peptides containing the asparagine-glycine-arginine (NGR) motif are recognized by CD13/aminopeptidase N (APN) receptor isoforms that are selectively overexpressed in tumor neovasculature. Spontaneous decomposition of NGR peptides can result in isoAsp derivatives, which are recognized by RGD-binding integrins that are essential for tumor metastasis. Peptides binding to CD13 and RGD-binding integrins provide tumor-homing, which can be exploited for dual targeted delivery of anticancer drugs. We synthesized small cyclic NGR peptide-daunomycin conjugates using NGR peptides of varying stability (c[KNGRE]-NH2, Ac-c[CNGRC]-NH2 and the thioether bond containing c[CH2-CO-NGRC]-NH2, c[CH2-CO-KNGRC]-NH2). The cytotoxic effect of the novel cyclic NGR peptide-Dau conjugates were examined in vitro on CD13 positive HT-1080 (human fibrosarcoma) and CD13 negative HT-29 (human colon adenocarcinoma) cell lines. Our results confirm the influence of structure on the antitumor activity and dual acting properties of the conjugates. Attachment of the drug through an enzyme-labile spacer to the C-terminus of cyclic NGR peptide resulted in higher antitumor activity on both CD13 positive and negative cells as compared to the branching versions.


HIV stigma and viral load among African-American women receiving treatment for HIV.
African-American women are more likely than other women in the United States to experience poor HIV-related health; HIV stigma may contribute to these outcomes. This study assessed the relationship between HIV stigma and viral load, over time, among a sample of African-American women receiving treatment for HIV, and explored social support and depressive symptoms as mediators. Secondary analysis of longitudinal data. Data came from a randomized trial of an intervention to reduce HIV stigma among African-American women in HIV care in Chicago, Illinois and Birmingham, Alabama. Sociodemographic and psychosocial data were collected at up to six study visits over 14 months. Viral loads were extracted from medical records during the study period. Generalized linear mixed effects models were used to estimate associations among overall, internalized, and enacted HIV stigma and viral load over time. Mediation analyses were used to estimate indirect effects via social support and depressive symptoms. Data from 234 women were analyzed. Overall HIV stigma was significantly associated with subsequent viral load (adjusted β = 0.24, P = 0.005). Both between-subject (adjusted β = 0.74, P < 0.001) and within-subject (adjusted β = 0.34, P = 0.005) differences in enacted stigma were associated with viral load. Neither social support nor depressive symptoms were statistically significant mediators. Ongoing experiences of HIV stigmatization may contribute to increased viral load among African-American women in primary HIV care. Interventions should aim to alleviate the consequences of stigma experienced by patients and prevent future stigmatization.


Cosmology in the laboratory: defect dynamics in liquid crystals.
Liquid crystals are remarkably useful for laboratory exploration of the dynamics of cosmologically relevant defects. They are convenient to work with, they allow the direct study of the "scaling solution" for a network of strings, and they provide a model for the evolution of monopoles and texture. Experiments described here support the simple "one-scale" model for cosmic string evolution, as well as some qualitative predictions of string statistical mechanics. The structure of monopoles and their apparent cylindrical but not spherical symmetry is discussed. A particular kind of defect known as texture is described and is shown to have a dynamical instability-it can decay into a monopole-antimonopole pair. This decay process has been observed occurring in the liquid crystal, and studied with numerical simulations.


The occurrence of genital mycoplasmas in babies with and without respiratory distress.
Ureaplasma urealyticum organisms (ureaplasmas) were isolated from throat swabs and/or gastric aspirates taken from 22.5% of babies with respiratory distress in a special care unit. The organisms were isolated most frequently (33%) from a small number of babies with severe distress. However, they were recovered only a little less often (26%) from babies without respiratory distress in the unit, and from 19% of healthy babies, all of the aforementioned babies having been delivered vaginally. The numbers of organisms isolated from babies in the various groups were similar. There was, therefore, no clear evidence that ureaplasmas, nor M. hominis which was isolated from two babies only, were associated with respiratory distress. This finding was supported by the isolation of ureaplasmas from only one of 16 babies born by caesarian section, seven of whom developed respiratory distress but were ureaplasma-negative.


Influence of implant abutment angulations and two types of fibers on the fracture resistance of ceramage single crowns.
To assess the effect of three implant abutment angulations and two types of fibers on the fracture resistance of overlaying Ceramage single crowns. Three groups, coded A to C, with different implant abutment angulations (group A/0°, group B/15°, and group C/30° angulation) were restored with 45 overlay composite restorations; 15 Ceramage crowns for each angulation. Groups A, B, and C were further subdivided into three subgroups (n = 5) coded: 1, crowns without fiber reinforcement; 2, crowns with Connect polyethylene reinforcement; and 3, crowns with Interlig glass reinforcement. All crowns were constructed by one technician using the Ceramage System. The definitive restorations (before cementation) were stored in distilled water at mouth temperature (37°C) for 24 hours prior to testing. Before testing, the crowns were cemented using Temp Bond. The compressive load required to break each crown and the mode of failure were recorded. The speed of testing was 1 mm/min. The results were statistically analyzed by two-way ANOVA (p < 0.05). The tested crowns were examined using a stereomicroscope at 40×, and selected crowns (five randomly selected from each group) were further examined by scanning electron microscopy (SEM) to reveal the composite-fiber interface. Fracture resistance of single crowns was not affected (p > 0.05) by the different abutment angulations chosen (0°, 15°, 30°) or fiber reinforcement (Connect and Interlig fibers). Crowns in group A exhibited average loads to fracture (N) of A1 = 843.57 ± 168.20, A2 = 1389.20 ± 193.40, and A3 = 968.00 ± 387.53, which were not significantly different (p > 0.05) from those of groups B (B1 = 993.20 ± 327.19, B2 = 1471.00 ± 311.68, B3 = 1408.40 ± 295.07), or group C (C1 = 1326.80 ± 785.30, C2 = 1322.20 ± 285.33, C3 = 1348.40 ± 527.21). SEM images of the fractured crowns showed that the origin of the fracture appeared to be located at the occlusal surfaces of the crowns, and the crack propagation tended to extend from the occlusal surface towards the gingival margin. Implant abutment angulations of 0°, 15°, and 30° did not significantly (p > 0.05) influence the fracture resistance of overlaying Ceramage single crowns constructed with or without reinforcing fibers. The two types of fibers used for reinforcement (Connect and Interlig) had no effect (p > 0.05) on the fracture resistance of overlaying Ceramage single crowns.


Pharmacokinetics of single-dose administration of tinidazole in unweaned calves.
In a crossover trial, 7 healthy, 7- to 29-day-old, unweaned Finnish Ayrshire calves were given a single dose of 20 mg of tinidazole/kg of body weight, IV, and a single dose of 25 mg of tinidazole/kg orally. Blood samples were collected serially, and serum concentration of tinidazole was measured by use of high-performance liquid chromatography. Serum concentration vs time data were analyzed by use of the statistical moment theory. Terminal half-life was 394 minutes after IV administration and 524 minutes (harmonic mean) after oral administration. The corresponding system moment mean residence times were 542 +/- 61.8 minutes and 812 +/- 117 minutes (arithmetic mean +/- SD), respectively. Estimated volume of distribution at steady state and total body clearance were 0.74 +/- 0.05 L/kg and 1.37 +/- 0.13 ml/min/kg, respectively. Tinidazole was rapidly and totally absorbed from the gastrointestinal tract. Mean absorption time was 270 +/- 160 minutes, and the observed peak serum concentration was detected at 240 minutes. Bioavailability was 99.5 +/- 3.9%.


Borderline Pathology of Childhood: Implications of Early Axis II Diagnoses.
A personality pathology framework may be useful in the diagnosis and treatment of children with chronic psychopathology and impairment in many domains of functioning. This paper presents the utility of such an approach through a description of research investigating borderline pathology of childhood (BPC). Literature regarding the phenomenology, risk factors, and outcomes of BPC and similar disorders is reviewed. Research conducted at the SMBD-Jewish General Hospital in Montreal has shown that children with BPC can be reliably identified via chart review, and that they exhibit a pattern of risk factors similar to that of adults with borderline personality disorder, such as psychological trauma and deficits in executive function. Preliminary results of a follow-up study in adolescence suggests that these children remain more functionally impaired than a comparison group. Our current research investigates neuropsychological deficits and their relationship to trauma in children with BPC. We are also exploring whether a similar pattern can be observed in their parents. We conclude that BPC symptom patterns may diagnostically define a group of high risk children and may eventually guide our approach to early intervention.


Pathophysiology of and therapeutic strategies for hypertension in pregnancy.
Approximately 8% to 10% of pregnancies are complicated by hypertension. The disease, whether it first appears during gestation or was present prior to conception, puts both mother and baby at risk. The fetal risks include death in utero, poor growth, and prematurity. The risks to the mother are more difficult to assess, but intracranial bleeding is the most common cause of death. This review examines some of the physiological changes that occur in normal pregnancy and defines the hypertensive disorders of pregnancy. The recent data regarding pharmacologic and nonpharmacologic therapies for the treatment of hypertension in pregnancy are discussed, and comments as to the prophylaxis of preeclampsia are noted.


Obstructive sleep apnoea and oral breathing in patients free of nasal obstruction.
Although there is an association between nasal obstruction, oral breathing and obstructive sleep apnoea syndrome (OSAS), it remains unknown whether increased oral breathing occurs in patients with OSAS who are free of nasal obstruction. The present study evaluated the relationship between breathing route and OSAS in patients without nasal obstruction. The breathing route of 41 snorers (25 male; aged 26-77 yrs) with normal nasal resistance was examined during overnight polysomnography using a nasal cannula/pressure transducer and an oral thermistor. In total, 28 patients had OSAS (apnoeics) and 13 patients were simple snorers. Apnoeics had a higher percentage of oral and oro-nasal breathing epochs. Oral and oro-nasal breathing epochs were positively related with apnoea/hypopnoea index (AHI) and duration of apnoeas/hypopnoeas and inversely related to oxygen saturation. Additionally, oro-nasal breathing epochs correlated with body mass index (BMI). In multiple linear regression analysis, oral breathing epochs were independently related only to AHI (r2 = 0.443), and oro-nasal breathing epochs were independently related to AHI (r2 = 0.736) and BMI (r2 = 0.036). In conclusion, apnoeics spent more time breathing orally and oro-nasally than simple snorers, and the apnoea/hypopnoea index is a major determinant of the time spent breathing orally and oro-nasally.


A rare cause of cyanosis in neonatal age: Cor triatriatum dexter.
Cor triatriatum dexter is an extremely rare congenital anomaly that is caused by the partitioning of the right atrium by a broad sheet of tissue due to the persistence of the right sinus venosus valve. We describe a rare case of prominent right sinus venosus valve (cor triatriatum dexter) with consequent right-to-left shunt across the patent foramen ovale in a newborn with significant cyanosis.


tagFinder: A Novel Tag Analysis Methodology That Enables Detection of Molecules from DNA-Encoded Chemical Libraries.
Available tools to analyze sequencing data coming from DNA-encoded chemical libraries (DELs) are often limited to in-house methods, which usually rely on strictly looking for the particular DEL structure used. Current methods do not take into account technological errors, such as library codification and sequencing errors, when detecting the sequences. The vast amount of data produced by next-generation sequencing of DEL screens is usually enough to extract the minimum information needed for compound identification. Here, we report a methodology to deconvolute encoding oligonucleotides, thus optimizing the sequencing power regardless of the library size, design complexity, or sequencing technology chosen. tagFinder is a highly flexible tool for fast tag detection and thorough DEL results characterization, which requires minimal hardware resources, scales linearly, and does not introduce any analytical error. The methodology can even deal with sequencing errors and PCR duplicates on single- or double-stranded DNA, enhancing the analytical detection and quantification of molecules and the informativeness of the entire process. Source code is available at https://github.com/jamigo/tagFinder .


The acromiohumeral and coracohumeral intervals are abnormal in rotator cuff tears with muscular fatty degeneration.
We sought to determine how various types of full-thickness rotator cuff tears, fatty degeneration of the rotator cuff muscles, duration of symptoms, and mechanism of injury affect the sizes of the acromiohumeral and coracohumeral intervals. We studied 206 shoulders with rotator cuff tears that had surgical treatment. The acromiohumeral interval (anteroposterior radiograph) and the coracohumeral interval (computed tomogram) were measured on preoperative imaging studies. An abnormal acromiohumeral interval was associated with multiple-tendon rotator cuff tears involving the infraspinatus, fatty degeneration of the supraspinatus or infraspinatus, and duration of symptoms longer than 5 years. An abnormal coracohumeral interval was associated with a combined tear of the supraspinatus and subscapularis and fatty degeneration of the infraspinatus or subscapularis. Fatty degeneration of the infraspinatus therefore was associated with an abnormal acromiohumeral interval and an abnormal coracohumeral interval. Evaluation of a patient who has a diminished acromiohumeral or coracohumeral interval should involve examination with computed tomography or magnetic resonance imaging of the rotator cuff tendons to determine the type of tear and of the rotator cuff muscles to determine the degree of fatty degeneration. Diagnostic study, Level II-1 (development of diagnostic criteria on basis of consecutive patients--with universally applied reference "gold" standard). See the Guidelines for Authors for a complete description of levels of evidence.


Molecular genetics of inherited susceptibility to intracellular parasites.
In the mouse, innate susceptibility to infection with mycobacteria is controlled by the Bcg host resistance locus. Phenotypically, the locus displays two alleles, a dominant resistance and a recessive susceptibility allele. The cell type expressing the resistance locus is the mature tissue macrophage. We have immortalized macrophages from Bcgr and Bcgs mice and found that macrophage cell lines of Bcgr origin, in comparison to those derived from Bcgs mice have an increased microbicidal activity and show increased expression of a number of molecules known to be associated with macrophage activation. This is in agreement with our earlier finding that Bcgr macrophages are at an advanced stage of macrophage priming for activation. The Bcg gene is located on the proximal region of mouse Chromosome 1. We have obtained a detailed genetic map in the vicinity of Bcg and identified three markers within 1 cM of the resistance locus. These three markers have been used for the generation of a physical map of this area of mouse Chromosome 1 and can be used as anchor points for the cloning of the Bcg host resistance gene. The chromosomal segment in the proximity of the Bcg locus in the mouse is precisely conserved on the telomeric region of the long arm of human Chromosome 2. Investigations of linkage of genetic markers present on human Chromosome 2q with susceptibility to tuberculosis have so far generated a LOD score of + 2.4. Linkage of Chromosome 2q markers with susceptibility to mycobacterial disease supports the existence of susceptibility genes in humans and suggests a human homologue of the mouse Bcg gene as a prime candidate for a human innate susceptibility locus.


Seroprevalence of Hepatitis-B infection amongst Taiwanese university students 18 years following the commencement of a national Hepatitis-B vaccination program.
In Taiwan, the nation-wide Hepatitis-B virus (HB) vaccination program was first launched in July 1984 and was directed to those infants born to hepatitis B surface antigen (HBsAg) carrier mothers in Taiwan. From July 1986 onwards, all infants born in Taiwan were immunized against HB. This study examined the HB-infection status amongst students at a Taiwanese university 18 years subsequent to the implementation of universal HB vaccination. A total of 1,969 new university entrants in 2005 were grouped into 1 of 3 distinct birth cohorts according to their HB-vaccination schedule (cohort-1 students born prior to July 1, 1984; cohort-3 students born subsequent to June 30, 1986) and were examined for their serum HBsAg, antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc) status. Immunity arising from vaccination was defined as an anti-HBs level 10 mIU/ml. We observed a trend toward a decreasing anti-HBc-positive rate and a decreasing HBsAg carrier rate from, respectively, 26.5 and 8.7% for cohort-1 to 4.7 and 1.7% for cohort-3 students. The prevalence of students featuring seronegativity for all three HB markers increased from 12.3% for cohort-1 to 48.8% for cohort-3 individuals. Amongst the 1,695 subjects revealing seronegativity for HBsAg and anti-HBc, their anti-HBs level was analyzed according to their birth year. The prevalence of students featuring a non-protective anti-HBs level increased from 11.9% for birth-year 1984 individuals to 48.2% for birth-year 1987 students. The introduction of HB vaccine has effectively reduced the transmission of HBV infection in Taiwan, 18 years subsequent to the commencement of the universal HB-vaccination program. A "waning-off" effect of anti-HBs seropositivity acquired from the HB vaccination program has also been observed.


Differential expression of angiopoietins 1 and 2 and their receptor Tie-2 in human endometrium.
Angiogenesis, the growth of new capillaries from pre-existing blood vessels, is a physiological process involved in both normal menstrual cycling and implantation of the embryo. So far, very little is known about the expression of angiopoietins, growth factors involved in angiogenesis, in human endometrium. Both angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are ligands for the endothelial cell-specific receptor tyrosine kinase Tie-2. In this study we determined the mRNA expression of Ang-1, Ang-2 and Tie-2 by quantitative competitive RT/(QC)-PCR (including specifically designed competitor cDNA) in biopsied human endometrium throughout the menstrual cycle. We detected the mRNA for the angiopoietins in 30 out of 32 endometrial biopsies (94%), covering early proliferative (n = 4), mid proliferative (n = 12), late proliferative (n = 3), early secretory (n = 3), mid secretory (n = 5) and late secretory (n = 3) phases. Analysis of the target/competitor ratios (QC-PCR) revealed that Ang-1 mRNA expression was significantly up-regulated (P = 0.027) during the secretory phase of the menstrual cycle. In contrast, the expression levels of both Ang-2 mRNA and Tie-2 mRNA showed only minor variations at different cycle stages. These findings were confirmed by the relative expression ratio of Ang-1 versus Ang-2 in a multiplex PCR. The expression of Ang-1, Ang-2 and Tie-2 mRNA was detected in both isolated endometrial epithelial and stromal cell fractions. Immunohistochemical localization of the proteins revealed qualitative differences in both cell type and cycle stage expression. In conclusion, the enhanced Ang-1 expression during the secretory phase might serve to stabilize the newly developed blood vessels.


Morphological and Crystalline Transitions in Monohydrous and Anhydrous Aripiprazole for a Long-Acting Injectable Suspension.
Many formulation and manufacturing processes can lead to morphological and crystalline transitions in many polycrystalline drugs, changing the properties of active pharmaceutical ingredients (APIs) such as solubility and physical stability which influence their therapeutic effects and safety and so limit their usefulness. Here, we report significant changes in crystal forms and morphology, including the shape and size of particles during the manufacture of off-white aripiprazole (APZ) dry powders used for long-acting and injectable suspensions. With the optimal top-down approach, powders were prepared by recrystallizing uniform monohydrous APZ (MA) and polycrystalline anhydrous APZ (AA) form III, characterized by thermal analysis, PXRD, and FT-IR. However, powders involving MA (MAP) with a lower mean size (2.126 μm), narrower distribution (span = 1.90), and higher stability compared with AA dry powders (AAP) were found to exhibit dehydration behavior and morphological changes after completion of the preparation processes based on the results of thermal analysis. In the case of APZ powders, we wished to obtain more information to guide in the industrial production and experimental design of suspensions in the future.


A Ypt/Rab GTPase module makes a PAS.
Organization of membrane micro-domains by Ypt/Rab GTPases is key for all membrane trafficking events in eukaryotic cells. Since autophagy is a membrane trafficking process, it was expected that these GTPases would play a role in autophagy as well. While evidence about participation of Ypt/Rabs in autophagy is beginning to emerge, the mechanisms by which they act in this process are still not clear. Moreover, it is still questionable if and how Ypt/Rabs coordinate autophagy with other cellular trafficking processes. Yeast Ypt1 and its mammalian homolog Rab1 are required for both endoplasmic reticulum (ER)-to-Golgi transport and autophagy, suggesting that they coordinate these two processes. In our recent paper, we identify Atg11, a bona fide phagophore assembly site (PAS) component, as a downstream effector of Ypt1. Moreover, we show that three components of a GTPase module--the Ypt1 activator, Trs85-containing TRAPP complex, Ypt1, and the Atg11 effector--interact on the PAS and are required for PAS formation during selective autophagy. We propose that Ypt/Rabs coordinate the secretory and the autophagic pathways by recruiting process-specific effectors.


Succession of the gut microbiota in the cockroach Blattella germanica.
The cockroach gut harbors a wide variety of microorganisms that, among other functions, collaborate in digestion and act as a barrier against pathogen colonization. Blattabacterium, a primary endosymbiont, lives in the fat body inside bacteriocytes and plays an important role in nitrogen recycling. Little is known about the mode of acquisition of gut bacteria or their ecological succession throughout the insect life cycle. Here we report on the bacterial taxa isolated from different developmental instars of the cockroach Blattella germanica. The bacterial load in the gut increased two orders of magnitude from the first to the second nymphal stage, coinciding with the incorporation of the majority of bacterial taxa, but remained similar thereafter. Pyrosequencing of the hypervariable regions V1-V3 of the 16S rRNA genes showed that the microbial composition differed significantly between adults and nymphs. Specifically, a succession was observed in which Fusobacterium accumulated with aging, while Bacteroides decreased. Blattabacterium was the only symbiont found in the ootheca, which makes the vertical transmission of gut bacteria an unlikely mode of acquisition. Scanning electron microscopy disclosed a rich bacterial biofilm in third instar nymphs, while filamentous structures were found exclusively in adults.


Nav1.1-Overexpressing Interneuron Transplants Restore Brain Rhythms and Cognition in a Mouse Model of Alzheimer's Disease.
Inhibitory interneurons regulate the oscillatory rhythms and network synchrony that are required for cognitive functions and disrupted in Alzheimer's disease (AD). Network dysrhythmias in AD and multiple neuropsychiatric disorders are associated with hypofunction of Nav1.1, a voltage-gated sodium channel subunit predominantly expressed in interneurons. We show that Nav1.1-overexpressing, but not wild-type, interneuron transplants derived from the embryonic medial ganglionic eminence (MGE) enhance behavior-dependent gamma oscillatory activity, reduce network hypersynchrony, and improve cognitive functions in human amyloid precursor protein (hAPP)-transgenic mice, which simulate key aspects of AD. Increased Nav1.1 levels accelerated action potential kinetics of transplanted fast-spiking and non-fast-spiking interneurons. Nav1.1-deficient interneuron transplants were sufficient to cause behavioral abnormalities in wild-type mice. We conclude that the efficacy of interneuron transplantation and the function of transplanted cells in an AD-relevant context depend on their Nav1.1 levels. Disease-specific molecular optimization of cell transplants may be required to ensure therapeutic benefits in different conditions.


Distal blood pressure as a predictor for the level of amputation in diabetic patients with foot ulcer.
The predictive value of distal blood pressure measurements for the level of amputation was studied prospectively in 161 consecutive diabetic patients with foot ulcers. The patients were treated as outpatients except for periods of surgery and when complications requiring hospital care occurred. All patients were treated pre- and postoperatively by the same multidisciplinary foot care team. Either ankle or toe blood pressure measurement was available in 86% of the patients. Incompressible arteries, ulcer or gangrene at the measuring site, previous amputation, poor general condition, and an emergency situation were factors that excluded standardized ankle and toe blood pressure measurements in 24% and 27% of the patients, respectively. An absolute lower ankle pressure level of 50 mm Hg was found, below which a minor amputation was never sufficient to achieve healing. An ankle pressure below 75 mm Hg was seldom sufficient, and at or above that pressure level, the ankle pressure had no predictive value in this respect. At a toe pressure below 15 mm Hg, a minor amputation was seldom sufficient. Ankle and toe pressure indices gave no further information.


Further Insight into the Effectiveness of a Behavioral Teacher Program Targeting ADHD Symptoms Using Actigraphy, Classroom Observations and Peer Ratings.
Objective: The Positivity and Rules program (PR program), a low-level behavioral teacher program targeting symptoms of attention-deficit/hyperactivity disorder (ADHD), has shown positive effects on teacher-rated ADHD symptoms and social functioning. This study aimed to assess whether program effects could be confirmed by instruments assessing classroom behavior other than teacher-ratings, given teachers' involvement with the training. Methods: Participants were 114 primary school children (age = 6-13) displaying ADHD symptoms in the classroom, who were randomly assigned to the treatment (n = 58) or control group (n = 65). ADHD symptoms were measured using classroom observations and actigraphy, and peer acceptance was measured using peer ratings. Intention-to-treat multilevel analyses were conducted to assess program effects. Results: No beneficial program effects were found for any of the measures. Conclusion: The earlier beneficial program effects on both ADHD symptoms and social functioning reported by teachers, may be explained by a change in the perception of teachers rather than changes in the child's behavior. Other methodological explanations are also discussed, such as differences between instruments in the sensitivity to program-related changes. The current study underlines the importance of using different measures of classroom behavior to study program effects. ClinicalTrials.gov registration number: NCT02518711.


Time-efficient sparse analysis of histopathological whole slide images.
Histopathological examination is a powerful standard for the prognosis of critical diseases. But, despite significant advances in high-speed and high-resolution scanning devices or in virtual exploration capabilities, the clinical analysis of whole slide images (WSI) largely remains the work of human experts. We propose an innovative platform in which multi-scale computer vision algorithms perform fast analysis of a histopathological WSI. It relies on application-driven for high-resolution and generic for low-resolution image analysis algorithms embedded in a multi-scale framework to rapidly identify the high power fields of interest used by the pathologist to assess a global grading. GPU technologies as well speed up the global time-efficiency of the system. Sparse coding and dynamic sampling constitute the keystone of our approach. These methods are implemented within a computer-aided breast biopsy analysis application based on histopathology images and designed in collaboration with a pathology department. The current ground truth slides correspond to about 36,000 high magnification (40×) high power fields. The processing time to achieve automatic WSI analysis is on a par with the pathologist's performance (about ten minutes a WSI), which constitutes by itself a major contribution of the proposed methodology.


The genetics of hepatitis C virus underlie its ability to escape humoral immunity.
Hepatitis C virus (HCV) is a leading cause of chronic liver disease, and efforts to develop therapeutic vaccine strategies have been limited by immune escape due to HCV variants that are resistant to current vaccines or HCV variants that rapidly acquire new resistance-conferring mutations. Recently, the crystal structure of the viral envelope protein E2 region was resolved as well as how E2 docks to the host CD81 protein; therefore, antibodies that block this interaction should prevent viral entry into host cells. In this issue of the JCI, Bailey and colleagues show that immune escape of HCV can occur by naturally occurring polymorphisms in E2 that are distinct from those at mapped sites of antibody binding. These data reveal alternative mechanisms of resistance that need to be considered in both natural viral escape as well as in rationale vaccine design against HCV.


Physiological relationships of the early posthatch performance of broilers to their embryo and eggshell characteristics.
Relationships between physiological parameters of early posthatch chicks with their corresponding egg and embryo parameters were examined in progeny of young broiler breeders. Four hundred and 80 broiler hatching eggs that were obtained from a 29-wk-old Ross 308 breeder flock were incubated on 8 replicate tray levels of an incubator until hatch. Between 10.5 and 18.5 d of incubation, internal (T(emb)) and external (T(ext)) egg temperatures were recorded twice daily using temperature transponders. Beginning at 18.5 d, the eggs were individually monitored for hatch every 12 h. Average T(emb), T(ext), and average daily incubational egg weight loss (EWL) for the 10.5- to 18.5-d incubation period were used to calculate eggshell water vapor conductance (G(H2O)), specific G(H2O) (g(H2O); G(H2O) adjusted to 100 g of set egg weight basis), and a G(H2O) constant (K(H2O)) for each egg. Chicks were grown out for 10 d in pens of a single battery brooder. In each pen, on d 3 posthatch, carcasses, yolk sac, liver, and pipping muscle samples were collected from at least 2 chicks that hatched from eggs implanted with transponders for determination of their relative weights and moisture concentrations. Livers and pipping muscles were also analyzed for glucose, glycogen, fat, and protein concentrations. Yolk sac weight as a percentage of chick BW (YW) and its moisture concentration (YSM) were positively correlated with T(emb). Egg g(H2O) was positively correlated with chick carcass moisture concentration and its relative weight as a percentage of set egg weight, but it was negatively correlated with YW. The positive functional relationship between T(emb) and incubation length may be mediated via their common positive relationships to YSM. A negative correlation was observed between percentage EWL and relative BW on d 0 and 0.5 posthatch for chicks hatched from unimplanted eggs. The results suggest that a higher g(H2O) results in an increased metabolism of the broiler embryo, which subsequently increases growth and yolk sac absorption in broiler chicks through 3 d posthatch.


Total elbow arthroplasty for primary osteoarthritis.
Primary osteoarthritis of the elbow is a less common indication for total elbow arthroplasty (TEA). Higher complication rates in younger, active patients may offset short-term improvements in pain and function. The purpose of this study was to determine pain relief, functional outcomes, complications, and survival of TEA in this population. Between 1984 and 2011, 20 consecutive TEAs were performed for primary elbow osteoarthritis. Two patients died before the 2-year follow-up. Mean age at surgery was 68 years (range, 51-85 years). Outcome measures included pain, motion, Mayo Elbow Performance Score, satisfaction, complications, and reoperations. Mean follow-up was 8.9 years (range, 2-20 years). Three elbows sustained mechanical failures. Complications included intraoperative fracture (n = 2), wound irrigation and débridement (n = 1), bony ankylosis (n = 1), humeral loosening (n = 1), humeral component fracture (n = 1), and mechanical failure of a radial head component (n = 1). Fifteen elbows without mechanical failure were examined clinically. Pain improved from 3.6 to 1.5 (P < .001). Range of motion remained clinically unchanged (P > .05), with preoperative flexion contractures not improving. Mayo Elbow Performance Scores were available for 13 elbows without mechanical failure, averaging 81.5 points (range, 60-100 points); these were graded as excellent (n = 5), good (n = 2), and fair (n = 6). Subjectively, all patients without mechanical failure were satisfied. TEA represents a reliable surgical option for pain relief in patients with primary osteoarthritis. However, restoration of extension is not always obtained, indicating that more aggressive soft tissue releases or bony resection should be considered. Complications occurred in a large number of elbows, but mechanical failure was low considering the nature of this population and the length of follow-up.


Evaluation of a multiplex human immunodeficiency virus-1, hepatitis C virus, and hepatitis B virus nucleic acid testing assay to detect viremic blood donors in northern Thailand.
Screening of blood donors with nucleic acid testing (NAT) for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) has been implemented recently in the United States. There are limited data, however, on the additional NAT yield of donors in developing countries in Asia where the prevalence of infection is higher. In addition, data on hepatitis B virus (HBV) NAT in high prevalence areas are minimal. A total of 5083 whole-blood donors at the Chiang Mai University Hospital, Thailand, blood bank were evaluated with a commercially available NAT assay (Procleix Ultrio, Gen-Probe, Inc.) to screen individual donations. No NAT yield cases were found for HIV-1 or HCV. There were 17 samples with discrepant HBV DNA NAT and hepatitis B surface antigen (HBsAg) tests, however. Seven of these were HBV DNA NAT-positive, HBsAg-negative; of these 7, 1 was NAT-positive at baseline, but negative on follow-up, and considered a false-positive, 1 had an acute infection, and 5 had chronic prevalent HBV infections, for a NAT yield of 6 in 4798 HBsAg negative donors (1:800). In addition there were 10 NAT-negative, HBsAg-positive serum samples. All were anti-hepatitis B core antigen immunoglobulin G-positive; on testing with a more sensitive NAT target capture assay, 5 were positive (1.8-20.6 IU/mL) and 5 were negative. Multiplex NAT screening of individual-donor serum samples in Northern Thailand detected approximately 1 per 800 HBV NAT-positive, HBsAg-negative donors. The especially high prevalence of HBV infection in Thailand and other Asian countries suggests that HBV NAT screening of donors will be more cost-effective than in other areas.


A Descriptive Report of Early Mobilization for Critically Ill Ventilated Patients with Cancer.
Early mobilization protocols have been successfully implemented to improve function in critically ill patients; however, no study has focused on the oncology population. To investigate the feasibility of early mobilization and describe the rehabilitation interventions and discharge outcomes in a cohort of critically ill patients with cancer. Retrospective review. A retrospective analysis of patients with cancer who participated in occupational and physical therapy while on mechanical ventilation utilizing an institutional early mobilization protocol from June 2010 - July 2011, was completed. Demographic and clinical variables were abstracted, as well as occupational and physical therapy interventions. A cohort of 42 cancer patients on mechanical ventilation in the mixed medical/surgical intensive care unit of a comprehensive cancer center received early mobilization during the study period. The majority of participants demonstrated improved cognitive and functional status from the intensive care unit to hospital discharge. There were no reported adverse events during the occupational and physical therapy sessions. Among the 30 hospital survivors, 53% required continued rehabilitation services in their home environment and 40% were transferred to a rehabilitation facility. Due to the small sample size, these findings are not generalizable to all critically ill cancer patients. There was no post-acute care follow-up of cognitive and physical functional performance. Early mobilization appears feasible in addressing the cognitive and functional needs of oncology patients in the intensive care unit.


Diagnosis and Treatment of Tuberous Sclerosis Manifestations in Children: A Multicenter Study.
Tuberous sclerosis complex (TSC) is a genetic disease with a significant morbidity and mortality. We conducted a retrospective analysis of two cohorts (Vall d'Hebron University Hospital [HVH], Barcelona, Spain, 1982-2015, and at Saarland University Medical Center [UKS], Homburg, Germany, 1998-2015) to assess prevalence and treatment of TSC associated manifestations and to evaluate if the follow-up was in line with published recommendations. This was considered if more than 15% of patients did not receive adequate examination with regard to potential organ involvement. A definite diagnosis was made in 52 patients (96%), and a possible diagnosis was made in 2 patients (4%). Thirty-four (63%) patients were from HVH and 20 (37%) from UKS. Median age at first presentation was 6 months (interquartile range: 0-38 months), and median time of follow-up was 6 years (interquartile range: 2-13 years). Clinical symptoms that led to a diagnosis of TSC were cardiac rhabdomyoma (22/54), epilepsy (20/54), and cutaneous manifestations (4/54). Assessment of neuropsychiatric, renal, and ocular manifestations was inadequate in both hospitals, whereas cutaneous manifestation was inadequate at UKS only. Our data demonstrate insufficient examinations in a substantial number of TSC patients with regard to neuropsychiatric, renal, ocular, and cutaneous manifestations. The recently published guidelines may prove valuable in establishing a more comprehensive approach.


Nanoparticle-based hyperthermia, a local treatment modulating the tumor extracellular matrix.
The structural complexity and physical properties of the tumor microenvironment negatively affect the penetration and efficiency of conventional anticancer drugs. While previously underestimated, the tumor microenvironment now becomes a potential target for cancer treatment. This microenvironment can be modulated either systemically by pharmacological means, or locally, through physical effects mediated by certain nanoparticles. Some of them, such as magnetic, plasmonic or carbon-based nanoparticles, can generate heat on demand in a spatially and temporally controlled manner. In addition, the nanoparticles can be either activated by light or magnetic stimuli. The impact of the resulting local heating can be observed on the ultrastructural level, as it strongly affects the organization of collagen fibers, and on the macroscopic level, since the thermal damages alter the mechanical properties of the tumor. Nanoparticle-based hyperthermia thus improves the effect of conventional anticancer drugs, as it allows their better penetration through the altered extracellular matrix. Here we suggest the use of nanoparticle-generated hyperthermia, obtained after magnetic or light activation, as an adjuvant treatment to prime the tumor microenvironment and improve the efficacy of chemotherapy.


Alignment of Visible-Light Optical Coherence Tomography Fibergrams with Confocal Images of the Same Mouse Retina.
In recent years, in vivo retinal imaging, which provides non-invasive, real-time, and longitudinal information about biological systems and processes, has been increasingly applied to obtain an objective assessment of neural damage in eye diseases. Ex vivo confocal imaging of the same retina is often necessary to validate the in vivo findings especially in animal research. In this study, we demonstrated a method for aligning an ex vivo confocal image of the mouse retina with its in vivo images. A new clinical-ready imaging technology called visible light optical coherence tomography fibergraphy (vis-OCTF) was applied to acquire in vivo images of the mouse retina. We then performed the confocal imaging of the same retina as the "gold standard" to validate the in vivo vis-OCTF images. This study not only enables further investigation of the molecular and cellular mechanisms but also establishes a foundation for a sensitive and objective evaluation of neural damage in vivo.


Effects on ribosomes of the substitution of spermidine or divalent cations for magnesium ions.
The inactivation of rat liver ribosomes (polysomes) resulting from the replacement of bound magnesium by spermidine has been studied using a dialysis method. Inactivation of the ribosomes (polysomes) occurred when more than 40% of the Mg2+ originally bound to ribosomes in the presence of 2 mM Mg2+ was replaced by spermidine. The polypeptide-synthesizing activity of polysomes was retained partially when Mg2+ was replaced by Mn2+ by dialysis. E. coli 30S ribosomal subunits were more resistant to inactivation due to the replacement of Mg2+ by spermidine than the 50S subunits.


Co-Exposure of Phenanthrene and the cyp-Inducer 3-Methylchrysene Leads to Altered Biotransformation and Increased Toxicity in Fish Egg and Larvae.
Polycyclic aromatic hydrocarbons (PAHs) have frequently been suspected of governing crude oil toxicity because of similar morphological defects in fish. However, PAH concentrations are often not high enough to explain the observed crude oil toxicity. We hypothesize that one PAH can enhance the metabolism and toxicity of another PAH when administered as a mixture. Early life stage Atlantic haddock (Melanogrammus aeglefinus) were in this study exposed to phenanthrene in the presence and absence of 3-methylchrysene that is known to induce the metabolic enzyme cytochrome P450 1A via cyp1a gene expression. Uptake, metabolism, and multiple toxicity endpoints were then measured in a time-course study up to 3 days post-hatching. Passive dosing provided aqueous concentrations ≈180 μg/L for phenanthrene and ≈0.6 μg/L for 3-methylchrysene, which resulted in tissue concentrations ≈60 μg/g ww for phenanthrene and ≈0.15 μg/g ww for 3-methylchrysene. The low concentration of 3-methylchrysene led to the elevated expression of cyp1a but no toxicity. Levels of phenanthrene metabolites were 5-fold higher, and morphological defects and cardiotoxicity were consistently greater when co-exposed to both compounds relative to phenanthrene alone. This work highlights the metabolic activation of PAH toxicity by a co-occurring PAH, which can lead to excess toxicity, synergistic effects, and the overproportional contribution of PAHs to crude oil toxicity.


Involvement of gamma-secretase in postnatal angiogenesis.
gamma-Secretase cleaves the transmembrane domains of several integral membrane proteins involved in vasculogenesis. Here, we investigated the role of gamma-secretase in the regulation of postnatal angiogenesis using gamma-secretase inhibitors (GSI). In endothelial cell (EC), gamma-secretase activity was up-regulated under hypoxia or the treatment of vascular endothelial growth factor (VEGF). The treatment of GSI significantly attenuated growth factor-induced EC proliferation and migration as well as c-fos promoter activity in a dose-dependent manner. In vascular smooth muscle cell (VSMC), treatment of GSI significantly attenuated growth factor-induced VEGF and fibroblast growth factor-2 (FGF-2) expression. Indeed, GSI attenuated VEGF-induced tube formation and inhibited FGF-2-induced angiogenesis on matrigel in mice as quantified by FITC-lectin staining of EC. Overall, we demonstrated that gamma-secretase may be key molecule in postnatal angiogenesis which may be downstream molecule of growth factor-induced growth and migration in EC, and regulate the expression of angiogenic growth factors in VSMC.


Residence rule flexibility and descent groups dynamics shape uniparental genetic diversities in South East Asia.
Social organization plays a major role in shaping human population genetic diversity. In particular, matrilocal populations tend to exhibit less mitochondrial diversity than patrilocal populations, and the other way around for Y chromosome diversity. However, several studies have not replicated such findings. The objective of this study is to understand the reasons for such inconsistencies and further evaluate the influence of social organization on genetic diversity. We explored uniparental diversity patterns using mitochondrial HV1 sequences and 17 Y-linked short tandem repeats (STRs) in 12 populations (n = 619) from mainland South-East Asia exhibiting a wide range of social organizations, along with quantitative ethno-demographic information sampled at the individual level. MtDNA diversity was lower in matrilocal than in multilocal and patrilocal populations while Y chromosome diversity was similar among these social organizations. The reasons for such asymmetry at the genetic level were understood by quantifying sex-specific migration rates from our ethno-demographic data: while female migration rates varied between social organizations, male migration rates did not. This unexpected lack of difference in male migrations resulted from a higher flexibility in residence rule in patrilocal than in matrilocal populations. In addition, our data suggested an impact of clan fission process on uniparental genetic patterns. The observed lack of signature of patrilocality on Y chromosome patterns might be attributed to the higher residence flexibility in the studied patrilocal populations, thus providing a potential explanation for the apparent discrepancies between social and genetic structures. Altogether, this study highlights the need to quantify the actual residence and descent patterns to fit social to genetic structures.


Effects of clopidogrel on vascular proliferation and apoptosis in an atherosclerotic rabbit model.
Inflammation, vascular proliferation. and apoptosis contribute to the process of atherosclerosis. Clopidogrel has been used to treat atherosclerosis; however, the mechanism is not entirely known. Compared with those of atorvastatin, we determined effects of clopidogrel on inflammatory factors, vascular proliferation, and apoptosis in an atherosclerosis rabbit model. New Zealand white rabbits were fed a normal diet or a high cholesterol diet for 7 weeks. The right iliac artery of animals except those in the negative control group were balloon-injured 1 week after initiation of the diet, and groups of animals were treated with clopidogrel (4 mg/kg per day), atorvastatin (2.5 mg/kg per day), or placebo (positive control group) for 6 weeks. We found that the placebo group had significant progression of atherosclerosis compared with the negative control group. In contrast, clopidogrel- or atorvastatin-treated rabbits showed a significant reduction in progression of atherosclerosis, including a low expression of high sensitivity C-reactive protein and platelet-derived growth factor, a reduced intima thickness, and reduced ratio of bcl-2/bax in the vascular wall. These results suggest that clopidogrel can retard the progression of established lesions that is related to inhibiting inflammation, cell proliferation, and promotion of cell apoptosis.


Are there differences between older persons who screen positive on the CAGE questionnaire and the Short Michigan Alcoholism Screening Test-Geriatric Version?
To determine (1) the extent of agreement between the CAGE (acronym for cut down, annoyed by criticism, guilty about drinking, eye-opener drinks) and the Short Michigan Alcoholism Screening Test-Geriatric Version (SMAST-G) in identifying older persons who may have possible alcohol use disorders (AUDs) and (2) whether persons identified as having possible AUDs by each of these screening measures differ in their drinking, demographic, or health-related characteristics. Secondary analysis of a cross-sectional study using data from a self-administered mailed survey sample. Three organizations were surveyed: (1) members of the American Association of Retired Persons and, in southern California, (2) managed care enrollees in a large medical group and (3) attendees of a community-based senior health center. One thousand eight hundred eighty-nine persons aged 55 and older completing a health risk appraisal for older persons (Health Risk Appraisal for the Elderly (HRA-E)). The HRA-E included items on drinking behaviors (including amount of alcohol use, the CAGE, and the SMAST-G) and health and demographic characteristics. Twenty-six percent of all persons screened positive on the CAGE or the SMAST-G. Fewer than half of all persons screening positive on either the CAGE or the SMAST-G, screened positive on both measures. Among current drinkers, persons screening positive on the SMAST-G alone drank less than persons screening positive on the CAGE alone, and these persons drank less than those screening positive on both the SMAST-G and the CAGE. More men screened positive on the CAGE alone than on the SMAST-G alone. Fewer than half of persons screening positive on either the CAGE or the SMAST-G screened positive on both measures, suggesting that these instruments may be capturing different aspects of unsafe drinking. A screening strategy employing both brief measures may identify more AUDs among older persons having differing demographic and health characteristics.


Psoriatic architecture constructed by epidermal remodeling.
Epidermal remodeling is the concept that epidermal architecture is determined by a simple self-organizing mechanism; epidermal hyperproliferation constructs typical psoriatic architecture. This is based on the assumption that the enlargements in both the two-dimensional proliferative compartment (basal cell layer) and three-dimensional whole epidermal volume coexist. During this process, the dermal papillae become markedly, but passively, expanded by enlargement of the proliferative compartment. This creates a considerable shrinkage force against the crowded basal cell layer, which is forced to lose adherence to the dermal extracellular matrix (ECM). This results in anoikis, a type of apoptosis characterized by cell detachment, and, consequently, a markedly diminished epidermal turnover time in psoriasis. The papillary shrinkage force also explains the fact that dermal papillary height does not exceed a certain limit. At the cessation of hyperproliferation a normalisation remodeling takes place toward normal tissue architecture. Thus the concept of epidermal remodeling explains the self-organizing mechanism of the architectural change in psoriasis, which is essentially a reversible disorder depending on epidermal hyperproliferation.


Interactions of antibiotics with phagocytes in vitro.
The goal of antimicrobial therapy is to eliminate invading bacteria both in the extracellular and intracellular environment. Thus, recent work has focused on the ability of various antibiotics to enter phagocytic cells and kill intracellular pathogens, since bacteria which survive within phagocytes may often produce prolonged or recurrent infections. In the last ten years the antibiotic modulation of phagocytic cell functions has become the subject of our major investigational activity. Taking into account that entry of antibiotics into phagocytes is necessary for activity against intracellular organisms, we examined the uptake of 11 radiolabelled antibiotics by macrophages. Penicillins and cephalosporins were taken up poorly by phagocytes. Teicoplanin was efficiently concentrated by macrophages, achieving intracellular concentrations higher than those in the surrounding extracellular medium. Roxithromycin was more markedly accumulated within phagocytes than was erythromycin, depending upon an active transport mechanism. Antitubercular drugs were concentrated approximately twofold in the macrophages. Besides, since antibiotics that act on phagocytosed bacteria have clinical advantages, we evaluated the direct action of the above mentioned drugs on the macrophage, by determining their interference with its functions or their potentiation of both phagocytosis and killing of bacteria.


Coprinopsis cinerea intracellular lactonases hydrolyze quorum sensing molecules of Gram-negative bacteria.
Biofilm formation on fungal hyphae and production of antifungal molecules are strategies of bacteria in their competition with fungi for nutrients. Since these strategies are often coordinated and under control of quorum sensing by the bacteria, interference with this bacterial communication system can be used as a counter-strategy by the fungi in this competition. Hydrolysis of N-acyl-homoserine lactones (HSL), a quorum sensing molecule used by Gram-negative bacteria, by fungal cultures has been demonstrated. However, the enzymes that are responsible for this activity, have not been identified. In this study, we identified and characterized two paralogous HSL hydrolyzing enzymes from the coprophilous fungus Coprinopsis cinerea. The C. cinerea HSL lactonases belong to the metallo-β-lactamase family and show sequence homology to and a similar biochemical activity as the well characterized lactonase AiiA from Bacillus thuringiensis. We show that the fungal lactonases, similar to the bacterial enzymes, are kept intracellularly and act as a sink for the bacterial quorum sensing signals both in C. cinerea and in Saccharomyces cerevisiae expressing C. cinerea lactonases, due to the ability of these signal molecules to diffuse over the fungal cell wall and plasma membrane. The two isogenes coding for the C. cinerea HSL lactonases are arranged in the genome as a tandem repeat and expressed preferentially in vegetative mycelium. The occurrence of orthologous genes in genomes of other basidiomycetes appears to correlate with a saprotrophic lifestyle.


Cation-dependent assembly of hexagonal DNA origami lattices on SiO2 surfaces.
DNA origami nanostructures have emerged as functional materials for applications in various areas of science and technology. In particular, the transfer of the DNA origami shape into inorganic materials using established silicon lithography methods holds great promise for the fabrication of nanostructured surfaces for nanoelectronics and nanophotonics. Using ordered DNA origami lattices directly assembled on the oxidized silicon surface instead of single nanostructures would enable the fabrication of functional nanopatterned surfaces with macroscopic dimensions. Here, we thus investigate the assembly of hexagonal DNA lattices from DNA origami triangles on RCA-cleaned silicon wafers with hydroxylated surface oxide by time-lapse atomic force microscopy (AFM). Lattice assembly on the SiO2 surface is achieved by a competition of monovalent and divalent cations at elevated temperatures. Ca2+ is found to be superior to Mg2+ in promoting the assembly of ordered lattices, while the presence of Mg2+ rather results in DNA origami aggregation and multilayer formation at the comparably high Na+ concentrations of 200 to 600 mM. Furthermore, Na+ concentration and temperature have a similar effect on lattice order, so that a reduction of temperature can be compensated to some extent by an increase in Na+ concentration. However, even under optimized conditions, the DNA origami lattices assembled on the SiO2 surface exhibit a lower degree of order than equivalent lattices assembled on mica, which is attributed to a higher desorption rate of the DNA origami nanostructures. Even though this high desorption rate also complicates any post-assembly treatment, the formed DNA origami lattices could successfully be transferred into the dry state, which is an important prerequisite for further processing steps.


Self-assembly of high-nuclearity metal clusters: programmed expansion of a metallasiloxane cage to an octacopper(II) cluster.
The novel octanuclear copper(II) cluster [Cu6[(PhSiO2)6]2[NCCu(Me6tren)]2(MeOH)4]2+ (1) has been isolated as a perchlorate salt by reacting the hexacopper(II) metallasiloxane cage [Cu6[(PhSiO2)6]2(nBuOH)x] (x = 4, 6) with [Cu(Me6tren)CN]ClO4 in a methanol/chloroform mixture (Me6tren = tris(2-(dimethylamino)ethyl) amine). Crystal data for 1(ClO4)2 x MeOH: monoclinic, space group P2(1)/n (no. 14), a = 16.8490(3) angstroms, b = 22.2966(4) angstroms, c = 17.2508(3) angstroms, beta = 94.7658(5) degrees, V = 6458.3(2) angstroms3, Z = 2. The structure comprises a highly distorted hexagonal Cu6 array linked to two [Cu(Me6tren)] units via cyanide bridges. Magnetic measurements reveal that the addition of the copper cyanide complexes dramatically affects the magnetism of the Cu6 unit, whose ground spin state changes from S = 3 to S = 0.


Charge trapping in carbon nanotube loops demonstrated by electrostatic force microscopy.
Electronic devices made from carbon nanotubes (CNTs) can be greatly affected by substrate charges, which, for instance, induce strong hysteresis in CNT field effect transistors. In this work, electrostatic force microscopy (EFM) is employed to investigate single-walled nanotubes grown by chemical vapor deposition on SiO2 substrates. We demonstrate the use of this technique to gain quantitative information on the substrate charges. It is found that charge pools with densities around 10(-8) C/cm2 can be trapped inside nanotube loops for extended periods of time, showing that nanotubes can act as confining barriers for substrate charges. The trapped charges can be removed by scanning probe manipulation.