Extensive variations and basic features in the alcohol dehydrogenase-sorbitol dehydrogenase family.
Structural comparisons of sorbitol dehydrogenase with zinc-containing 'long' alcohol dehydrogenases reveal distant but clear relationships. An alignment suggests 93 positional identities with horse liver alcohol dehydrogenase (25% of 374 positions) and 73 identities with yeast alcohol dehydrogenase (20%). Sorbitol dehydrogenase forms a link between these distantly related alcohol dehydrogenases and is in some regions more similar to one of them that they are to each other. 43 residues (11%) are common to all three enzymes and include a heavy over-representation of glycine (half of all glycine residues in sorbitol dehydrogenase), showing the importance of space restrictions in protein structures. Four regions are well conserved, two in each domain of horse liver alcohol dehydrogenase. They are two segments close to the active-site zinc atom of the catalytic domain, and two in the central beta-pleated sheet strands of the coenzyme-binding domain. These similarities demonstrate the general importance of internal and central building units in proteins. Large variations affect a region adjacent to the third protein ligand to the active-site zinc atom in horse liver alcohol dehydrogenase. Such changes at active sites of related enzymes are unusual. Other large differences concern the segment around the non-catalytic zinc atom of horse liver alcohol dehydrogenase; three of its four cysteine ligands are absent from sorbitol dehydrogenase. Three segments with several exchanges correspond to a continuous region with superficial areas, inter-domain contacts and inter-subunit interactions in the catalytic domain of alcohol dehydrogenase. They may correlate with the altered quaternary structure of sorbitol dehydrogenase. Regions corresponding to top and bottom beta-strands in the coenzyme-binding domain of the alcohol dehydrogenase are also little conserved. Within sorbitol dehydrogenase, a large segment shows an internal similarity. The two distantly related alcohol dehydrogenases and sorbitol dehydrogenase form a triplet of enzymes illustrating basic protein relationships. They are ancestrally close enough to establish similarities, yet sufficiently divergent to illustrate changes in all but fundamental properties.


Reverse passive hemagglutination tests for rapid diagnosis of snake envenomation.
Reverse passive hemagglutination (RPHA) tests for the detection of six major poisonous snake venoms of Thailand were studied. Three different species of red blood cells i.e., sheep (SRBC), human (HRBC) and chicken (CRBC) were sensitized with protein A-affinity purified rabbit antivenom IgG using chromic chloride as a coupling reagent. The properties of these sensitized erythrocytes with regard to sensitivity, specificity, stability to venom enzymes and storage etc., were studied and compared. The sensitivities of the RPHA tests in venom detection were 2 to 635 ng/ml. Cross-reactions were observed with heterologous venoms at concentrations at least 62 times higher than those observed with homologous venoms. After treatment with glutaraldehyde, the coupled red blood cells showed reduced sensitivity but were stable at 4 degrees C from 1 to 12 months depending upon the antibody and the species of erythrocytes. The entire test required 60 to 120 min. The RPHA using fresh SRBC correctly identified various venoms in 48 of 59 (81.3%) serum samples and 16 of 26 (61.5%) wound swabs. Venom mis-identifications were made in 2 sera (3.4%). In a comparison of 24 paired serum and wound swab samples, more positive identifications were made with serum than with swab samples but the difference was not statistically significant (p > 0.05).


Resin-assisted solvothermal synthesis of transition metal-organic frameworks.
Cation-exchanged polymer resin beads have been used as a heterogeneous controlled-release source of metal cations in phase pure and/or high yielding solvothermal syntheses of novel transition metal-organic frameworks. The introduction of the resin beads has a dramatic effect on the outcome of solvothermal reactions. We report the syntheses of a series of transition metal-containing MOFs via the resin-assisted solvothermal methods, four novel MOFs are reported that could not be synthesised by traditional methods. These MOFs have been characterized using elemental analysis, powder XRD, single crystal XRD, FESEM, EPR, B.E.T. surface analysis, and solid state magnetic measurements.


General practitioners' clinical expertise in managing suicidal young people: implications for continued education.
Aim To examine general practitioners' (GPs) clinical expertise in assessing, communicating with, and managing suicidal young people aged 14-25 to inform the development of an educational intervention for GPs on youth suicide prevention. Suicide is the second leading cause of death for young people worldwide. GPs are ideally suited to facilitate early identification and assessment of suicide risk. However, GPs' levels of competence, knowledge, and attitudes towards suicidal young people have not yet been explored. A cross-sectional survey on GPs' levels of confidence in assessing and managing young people at risk of suicide; knowledge of risk factors and warning signs of suicide in young people; attitudes towards young suicidal people; and training preferences on managing suicide risk. Findings Seventy GPs completed the survey (30 males). The majority of GPs reported high levels of confidence in assessing and managing suicidality in young people. Experienced GPs demonstrated high levels of knowledge of suicide risk factors in young people but low levels of knowledge of warning signs that might indicate heightened risk. Although 48% of GPs disagreed that maintaining compassionate care is difficult with those who deliberately self-harm, GPs perceived communication with young people to be difficult, with one-third reporting frustration in managing those at risk of suicide. A total of 75% of GPs said they would be interested in receiving further training on assessing and managing young people at risk of suicide. The study has important implications for providing specialist training to support GPs in assessing and managing youth suicide risk and facilitating attitudinal change. GP education on youth suicide risk assessment and management should promote a holistic understanding and assessment of risk and its individual, social and contextual influences in line with clinical recommendations to facilitate therapeutic engagement and communication with young people.


Autologous stem cell transplantation in acute myocardial infarction: The ASTAMI randomized controlled trial. Intracoronary transplantation of autologous mononuclear bone marrow cells, study design and safety aspects.
Intracoronary transplantation of different cell populations has been used in acute myocardial infarction (AMI) with promising results. The primary objective of the Autologous Stem cell Transplantation in Acute Myocardial Infarction (ASTAMI) study is to test whether intracoronary transplantation of autologous mononuclear bone marrow cells (mBMC) improves left ventricular ejection fraction (LVEF) after anterior wall AMI. The ASTAMI study is a randomized, controlled, prospective study. One hundred patients with acute anterior wall ST-elevation myocardial infarction (STEMI) treated with acute percutaneous coronary intervention (PCI) are randomized in a 1:1 way to either intracoronary transplantation of autologous mBMC 5-8 d after PCI or to control. Left ventricular function, exercise capacity, biochemical status, functional class, quality of life and complications are validated at baseline and during a 12-month follow-up. By August 2004, out of 1004 patients with STEMI, 49 patients have been included in the study. Twenty-four patients have been randomized to intracoronary mBMC transplantation. Twenty patients had chest pain and 16 patients had ischemic ECG changes during the mBMC transplantation procedure. One patient had ventricular fibrillation 24 h after transplantation. Intracoronary transplantation of autologous mBMC in the acute phase after AMI is feasible and seems safe in the short term.


A case of hepatic angiosarcoma supplied by both hepatic artery and portal vein.
Liver neoplasms, whether they are benign or malignant, are usually fed by the hepatic artery. We experienced a case of hepatic angiosarcoma supplied by both hepatic artery and portal vein. Since there are currently no specific laboratory tests to diagnose hepatic angiosarcoma, it is important to detect suspect cases from imaging features. This unique hemodynamic property was detected on computed tomography (CT) during hepatic arteriography and CT during hepatic arterioportography. If any imaging examinations indicate the liver tumor to be fed by the portal vein, hepatic angiosarcoma should be suspected.


The human anionic antimicrobial peptide dermcidin induces proteolytic defence mechanisms in staphylococci.
Antimicrobial peptides (AMPs) represent a key component of innate host defence against bacterial pathogens. Bacterial resistance mechanisms usually depend on the characteristic positive charge of AMPs. However, several human cell types also produce anionic AMPs, mechanisms of resistance to which are poorly understood. Here we demonstrate that the skin commensal and leading nosocomial pathogen Staphylococcus epidermidis senses and efficiently inactivates the anionic AMP dermcidin. Dermcidin induced differential expression of global regulatory systems, leading to increased expression of proteases with the capacity to degrade dermcidin, particularly S. epidermidis SepA. A similar induction of extracellular proteolytic activity was found in Staphylococcus aureus, suggesting a common regulatory mechanism in staphylococci. Notably, human cationic AMPs also led to the activation of global regulators, but inactivation of dermcidin by SepA was much more effective than of the tested cationic peptides. The ability to react to the unusual, anionic dermcidin with effective countermeasures likely contributes to the extraordinary success of staphylococci as colonizers and infective agents on human epithelia. Our study indicates that staphylococci can react to human AMPs by specific mechanisms of resistance and establishes a crucial role for staphylococcal proteases in the interaction with human innate host defence.


An antiarrhythmic agent as a promising lead compound for targeting the hEAG1 ion channel in cancer therapy: insights from molecular dynamics simulations.
Experimental evidence suggests that hERG and hEAG potassium channels may serve as important cancer therapy targets because either of the channel blockade or inactivation by different methods leads to inhibition of cancer cells growth and proliferation. However, there is no known hEAG specific blocker, and hERG blockade leads to adverse cardiac side effects, although it is currently used in treating certain types of arrhythmias. There have been some attempts to explain the channels blockade by clofilium, an antiarrhythmic agent, and the results lead to different possible binding modes. This study investigates for the first time the potential of using clofilium as a lead compound for finding a novel cancer therapy agent which may target ion channels. The implied findings from a comparative assessment of literature studies were verified using molecular dynamics simulations. The results indicate a particular structural difference between the two channels that could provide a novel and realistic way of using clofilium analogs which may target the hEAG1 ion channel in cancer therapy.


Clinical trial of tolerance of HPA-23 in patients with acquired immune deficiency syndrome.
An open-label, multicenter clinical trial assessed the tolerance of HPA-23 (ammonium-21-tungsto-9-antimoniate) in patients with acquired immune deficiency syndrome. Sixty-nine patients were sequentially assigned to receive 0.25, 0.5, 1.0, or 2.0 mg of HPA-23 per kg intravenously 5 days per week for 8 weeks. HPA-23 was fairly well tolerated at doses of 1.0 mg/kg or less; nearly 60% of patients given 2.0 mg/kg discontinued treatment. Twenty-six patients discontinued treatment because of adverse events or concurrent illness. HPA-23 produced dose-related decreases in platelet count and increases in serum glutamine oxalacetic transaminase. There were no changes in immune system function, as determined by total lymphocyte count, T4-cell count, T8-cell count, and T4/T8 ratio. The effects of HPA-23 seemed to be more closely related to the total dose than to the daily dose. No improvement in the clinical status of the patients was observed during the 8 weeks of treatment.


The acceptability, feasibility, and preliminary effectiveness of a courier HIV-treatment delivery and SMS support intervention for young people living with HIV in South Africa.
Young people living with HIV (YPLWH) experience poorer rates of virological suppression compared to adults. Differentiated service delivery models directed to YPLWH are urgently needed. Participants were recruited from an HIV treatment clinic near Cape Town, South Africa. We conducted a longitudinal pilot study to examine the acceptability, feasibility, and preliminary effectiveness of a courier ART delivery and SMS support intervention to retain YPLWH (13-24 years) in care during COVID-19. YPLWH had the option to enroll in the courier service and were randomized 1:1 to receive adherence support via a weekly SMS. Modified Poisson regression was used to estimate the preliminary effectiveness of the courier intervention on viral suppression (HIV-1 RNA <200 copies/mL) at months 3 and 6. Among 215 participants, 82% elected to enroll in the courier ART service at baseline, 41% reported receiving a delivery in the past three months at month 3, and 49% reported receiving a delivery at month 6. Among those who received a delivery, most (91-100%) rated the intervention as acceptable. Participants who reported receiving a delivery in the past three months at month 3 were 1.26 (95% CI 1.05-1.54) times as likely to have a suppressed viral load at month 3 and 1.21 (0.99-1.48) times as likely at month 6, controlling for potential confounders. Findings reveal high uptake and acceptability of a courier ART intervention among YPLWH, as well as promising evidence for its effectiveness in increasing the probability of viral suppression. A fully powered trial is warranted.


What factors promote vaccine hesitancy or acceptance during pandemics? A systematic review and thematic analysis.
Examine the factors that promote vaccine hesitancy or acceptance during pandemics, major epidemics and global outbreaks. A systematic review and thematic analysis of 28 studies on the Influenza A/H1N1 pandemic and the global spread of Ebola Virus Disease. We found seven major factors that promote vaccine hesitancy or acceptance: demographic factors influencing vaccination (ethnicity, age, sex, pregnancy, education, and employment), accessibility and cost, personal responsibility and risk perceptions, precautionary measures taken based on the decision to vaccinate, trust in health authorities and vaccines, the safety and efficacy of a new vaccine, and lack of information or vaccine misinformation. An understanding of participant experiences and perspectives toward vaccines from previous pandemics will greatly inform the development of strategies to address the present situation with the COVID-19 pandemic. We discuss the impact vaccine hesitancy might have for the introduction and effectiveness of a potential COVID-19 vaccine. In particular, we believe that skepticism toward vaccines can still exist when there are no vaccines available, which is contrary to contemporary conceptualizations of vaccine hesitancy. We recommend conducting further research assessing the relationship between the accessibility and cost of vaccines, and vaccine hesitancy.


Adrenal insufficiency attributable to adrenal hemorrhage: long-term follow-up with reference to glucocorticoid and mineralocorticoid function and replacement.
To describe the long-term follow-up of acute adrenal insufficiency attributable to bilateral adrenal hemorrhage. We performed a retrospective review of medical records of four patients who underwent follow-up for 6(1/2) to 19 years. Despite published reports of more than 500 patients with bilateral massive adrenal hemorrhage through 2001, no long-term data assessing the continuing requirements for glucocorticoid and mineralocorticoid replacement are available. After follow-up of four patients with acute bilateral adrenal hemorrhage and glucocorticoid insufficiency for 6(1/2) to 19 years, we document the absence of need for long-term mineralocorticoid replacement on the basis of no occurrence of postural hypotension, normal electrolytes, normal baseline or cosyntropin-stimulated serum aldosterone levels, and generally, though not invariably, normal plasma renin activity levels. We further document the improvement in either or both baseline and cosyntropin-stimulated serum cortisol levels in three of the four patients and the ability of one patient to function normally without cortisol replacement for 4 years. Adrenal histologic findings in this last-mentioned patient revealed previously undescribed changes consistent with regeneration and myelolipoma. Finally, we confirm bilateral atrophic adrenal glands by computed tomography 5(1/2) to 11(1/2) years after bilateral adrenal hemorrhage in three of the four patients. Long-term follow-up of patients with acute adrenal insufficiency attributable to adrenal hemorrhage demonstrates, for the first time, absence of need for prolonged mineralocorticoid replacement and some improvement in endogenous glucocorticoid function in at least some of these patients.


Effects of highly purified structured lipids containing medium-chain fatty acids and linoleic acid on lipid profiles in rats.
The purpose of this study is to examine the effects of highly purified structured lipids on serum and liver lipid profiles in rats. We also investigated in vitro hydrolysis of lipid emulsions by porcine pancreas. Hydrolysis rates of medium chain (M)-linoleic (L)-medium chain (M) types were 2 to 3 times higher than those of L-M-L types. The diet containing structured lipids or corn oil was administered to rats for 4 weeks. There were no significant differences in growth and food efficiency. Serum cholesterol levels were significantly lower (P<0.05) in the 2-octanoyl-1,3-dilinoleoyl-glycerol, 2-linoleoyl-1,3-didecanoyl-glycerol, and 2-decanoyl-1,3-dilinoleoyl-glycerol groups than in the corn-oil group. Serum triglyceride levels were significantly lower (P<0.05) in rats fed L-M-L types than those in the other groups. Serum non-esterified fatty acid (NEFA) and beta-hydroxybutylate levels were significantly higher (P<0.01) in rats fed M-L-M types than those of the other groups. These results indicate that the feeding of highly purified L-M-L types could effectively improve serum and liver lipid profiles and that M-L-M types may be a preferable substrate for the pancreas and contribute to energy supply in rats.


Echinocytes in families with Duchenne muscular dystrophy.
The results of the present investigation have failed to confirm the suggestion that there is a significant increase in the proportion of echinocytes in preparation of fresh erythrocytes in patients with Duchenne muscular dystrophy and heterozygous carriers of this disorder.


Comparative analysis of two isocyanate-free urethane-based gels for antifouling applications.
Amphiphilic gels consisting of acrylamide (AAM)/2-hydroxyethyl methacrylate (HEMA), hexafluorobutyl methacrylate (HFBMA) and non-isocyanate urethane dimethacrylate (NIUDMA) of varying molecular weights were compared. A three-level Taguchi analysis was performed using the amount of AAM/HEMA, HFBMA, NIUDMA and reaction time as dependent variables to determine the optimal formulation of the gels with maximized toughness and elastic modulus. The results were compared with commercial AF/FR Intersleek® coatings (IS 700, IS 900 and IS 1100SR) for their antifouling performance against a marine microalga (Navicula incerta), a marine bacterium (Cellulophaga lytica) and adult barnacles (Amphibalanus amphitrite). The toughness, elastic modulus and strain at break of the optimized AAM gels ranged from 3 to7 MPa, 25 to 72 MPa and 80% to 170%, respectively, whereas those of the optimized HEMA gels ranged from 1 to 3 MPa, 13 to 23 MPa and 76% to 160%, respectively. The gels, particularly AHN(E9) and HHN(E12), showed reductions of attachment compared with IS700 of up to 93% and 58%, respectively.


Inflammatory cytokines induce production of CHI3L1 by articular chondrocytes.
Elevated levels of CHI3L1 (chitinase-3-like protein 1) are associated with disorders exhibiting increased connective tissue turnover, such as rheumatoid arthritis, osteoarthritis, scleroderma, and cirrhosis of the liver. This secreted protein is not synthesized in young healthy cartilage, but is produced in cartilage from old donors or patients with osteoarthritis. The molecular processes governing the induction of CHI3L1 are currently unknown. To elucidate the molecular events involved in CHI3L1 synthesis, we investigated two models of articular chondrocytes: neonatal rat chondrocytes, which do not express CHI3L1, and human chondrocytes, which express CHI3L1 constitutively. In neonatal rat chondrocytes, the inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 potently induced steady-state levels of CHI3L1 mRNA and protein secretion. Treatment of chondrocytes with TNF-alpha for as little as 1 h was sufficient for sustained induction up to 72 h afterward. Using inhibitors selective for the major signaling pathways implicated in mediating the effects of TNF-alpha and interleukin-1, only inhibition of NF-kappaB activation was effective in curtailing cytokine-induced expression, including after removal of the cytokine, indicating that induction and continued production of CHI3L1 are controlled mainly by this transcription factor. Inhibition of NF-kappaB signaling also abolished constitutive expression by human chondrocytes. Thus, induction and continued secretion of CHI3L1 in chondrocytes require sustained activation of NF-kappaB. Selective induction of CHI3L1 by cytokines acting through NF-kappaB coupled with the known restriction of the catabolic responses by CHI3L1 in response to these inflammatory cytokines represents a key regulatory feedback process in controlling connective tissue turnover.


Release of a prostaglandin E-like substance into mixed venous blood during endotoxin hypotension in cats.
An iv injection of E. coli endotoxin (10--15 mg/kg) produced biphasic hypotensive reaction in cats. The second phase of hypotension developed 5--10 min after the administration of endotoxin and was paralleled by an appearance of a substance contracting the chick rectum and rat colon which were bathed in mixed venous blood. On the basis of differential sensitivity of the assay organs to prostaglandins it was concluded that a prostaglandin E-like substance (PGEs) was released. Its peak concentration in blood was 1--3-5 ng/ml in terms of PGE2-like activity. Indomethacin (10 mg/kg) interrupted the liberation of PGEs into blood and at the same time a slow but steady increase in arterial blood pressure occured. The amelioration of endotoxin hypotension by indomethacin was abolished by an infusion of PGE2 at a rate of 20--100 ng/kg/min. It is suggested that the second phase of endotoxin hypotension in cats is mediated by a release of PGEs.


New Aggregation-Induced Emitters: Tetraphenyldistyrylbenzenes.
The synthesis of five novel distyrylbenzene (DSB) derivatives, featuring a central tetraphenylbenzene core, is reported. The targets show aggregation-induced emission (AIE), which, however, is substituent-dependent. For the pure hydrocarbon and derivatives that do not carry (+M) or (-M) substituents, classic AIE behavior is observed, that is, the DSBs are non-fluorescent in solution, but are highly fluorescent in cold matrices, upon aggregate formation in poor solvents and in the solid, crystalline state. If aldehyde or dibutylamino groups are attached in the para-position of the DSB unit, non-classic AIE-phores result. These are fluorescent both in dilute solution as well as in the solid state. Prolonged irradiation of the targets leads to benzotetraphene derivatives by a double cyclization.


An international survey on noninvasive ventilation use for acute respiratory failure in general non-monitored wards.
Use of noninvasive ventilation (NIV) for the treatment of patients with acute respiratory failure (ARF) has greatly increased in the last decades. In contrast, the increasing knowledge of its effectiveness and physician confidence in managing this technique have been accompanied by a declining number of available ICU beds. As a consequence, the application of NIV outside the ICU has been reported as a growing phenomenon. Previously published surveys highlighted a great heterogeneity in NIV use, clinical indications, settings, and efficacy. Moreover, they revealed a marked heterogeneity with regard to staff training and technical and organizational aspects. We performed the first worldwide web-based survey focused on NIV use in general wards for ARF. A questionnaire to obtain data regarding hospital and ICU characteristics, settings and modalities of NIV application and monitoring, estimated outcomes, technical and organizational aspects, and observed complications was developed. The multiple-choice anonymous questionnaire to be filled out online was distributed worldwide by mail, LinkedIn, and Facebook professional groups. One-hundred fifty-seven questionnaires were filled out and analyzed. Respondents were from 51 countries from all 5 continents. NIV application in general wards was reported by 66% of respondents. Treatments were reported as increasing in 57% of cases. Limited training and human resources were the most common reasons for not using NIV in general wards. Overall, most respondents perceived that NIV avoids tracheal intubation in most cases; worsening of ARF, intolerance, and inability to manage secretions were the most commonly reported causes of NIV failure. Use of NIV in general wards was reported as effective, common, and gradually increasing. Improvement in staff training and introduction of protocols could help to make this technique safer and more common when applied in general wards setting.


Natural autoantibodies in the serum of healthy women--a five-year follow-up.
Autoantibodies are often found among healthy individuals. The significance of these findings, regarding the potential development of overt autoimmune disease and the severity of such an eventuality, is as yet unclear. In order to elucidate these issues 506 healthy women were screened and 60 women of child-bearing age were found to posses high titres of various anti-nuclear antibodies. After a 5-year follow-up, 57 of these 60 women were found to have autoantibodies to a variety of autoantigens. Seven of the women had some symptoms that could be associated with the presence of the antibodies (i.e. arthritis, multiple abortions, Raynaud's phenomenon), however, none exhibited overt clinical signs of an autoimmune disease. Our study may point to the fact that in normal subjects (women aged 22-44 years) high titres of natural autoantibodies are not necessarily indicative of a high risk of developing an overt autoimmune condition, at least for a follow-up period of 5 years.


Right liver lobe/albumin ratio: contribution to non-invasive assessment of portal hypertension.
To study the value of biochemical and ultraso-nographic parameters in prediction of presence and size of esophageal varices. The study includes selected cirrhotic patients who underwent a complete biochemical workup, upper digestive endoscopic and ultrasonographic examinations. Albumin/right liver lobe diameter and platelet count/spleen diameter ratios were calculated. The correlation between calculated ratio and the presence and degree of esophageal varices was evaluated. Ninety-four subjects (62 males, 32 females), with a mean age of 52.32 +/- 13.60 years, were studied. Child-Pugh class A accounted for 42.6%, class B 37.2%, whereas class C 20.2%. Esophageal varices (OE) were not demonstrated by upper digestive endoscopy in 24.5%, while OE grade I was found in 22.3% patients, grade II in 33.0%, grade III in 16.0%, and grade IV in 4.3%. The mean value of right liver lobe diameter/albumin ratio was 5.51 +/- 1.82 (range from 2.76 to 11.44), while the mean platelet count/spleen diameter ratio was 1017.75 +/- 729.36 (range from 117.39 to 3362.50), respectively. Statistically significant correlation was proved by Spearman's test between OE grade and calculated ratios. The P values were 0.481 and -0.686, respectively. The right liver lobe diameter/albumin and platelet count/spleen diameter ratios are non-invasive parameters providing accurate information pertinent to determination of presence of esophageal varices, and their grading in patients with liver cirrhosis.


Symbolic attitude and reverie: problems of symbolization in children and adolescents.
In comparison to the 1970s and 1980s, we now treat more children and adolescents who, because they have had traumatic experiences of violence, child abuse, deprivation or chronic physical illness, are not able to adequately use their symbolizing function. The question is which qualities and which analytical attitude we should and can offer in analysis to help a child regain his or her capacity to symbolize, irrespective of how poorly developed or blocked this capacity may be. In contrast to Jung and some Jungians, the author argues that although the transcendent function is a 'natural process' and hence archetypally grounded as Jung maintained, the transcendent function does not work spontaneously. Rather it requires a matrix based on the child's earliest relationship, which can later be re-enacted in treatment. Jung's general concept of a 'symbolic attitude' can be complemented and focused in a specific way through the use of Bion's concept of 'reverie', which contributes in a fundamental way to symbol formation within the transference/countertransference. This idea is illustrated by clinical material from a nine-year-old boy who suffered from a severe congenital intestinal disease and was blocked in his capacity to symbolize. From the perspective of treatment technique, the author shows how the drawing of 'comic book' narratives in a reciprocal exchange was brought into the treatment. The drawings evolved in a way that he understood as a modified form of active imagination with children. The drawing process helped the boy gradually to develop a symbolic space in the therapy and to contain a psychic space in his mind.


An Exploratory Study of Intensive Neurofeedback Training for Schizophrenia.
Schizophrenia is a chronic and devastating brain disorder with ongoing cognitive, behavioral, and emotional deteriorated functions. Neurofeedback training, which enables the individuals to regulate their brain activity using a real-time feedback loop, is increasingly investigated as a potential alternative intervention for schizophrenia. This study aimed to explore the effect of short but intensive neurofeedback training for schizophrenic patients with difficulty for long-time training. A middle-aged woman with chronic schizophrenia completed the intensive training of alpha/beta2 (20-30 Hz) in four consecutive days with a total training duration of 13.5 hours. The results showed that her alpha/beta2 increased over sessions, and her behavior performance including short-term memory, mood, and speech pattern was improved at the end of neurofeedback training. Importantly, a 22-month follow-up found a dramatic improvement in both positive and negative symptoms. These positive outcomes suggest that such intensive neurofeedback training may provide new insight into the treatment of schizophrenia and thus deserves further study to fully examine its scope.


Broadly cross-reactive HIV-1-neutralizing human monoclonal Fab selected for binding to gp120-CD4-CCR5 complexes.
HIV-1 entry into cells involves formation of a complex between gp120 of the viral envelope glycoprotein (Env), a receptor (CD4), and a coreceptor, typically CCR5. Here we provide evidence that purified gp120(JR-FL)-CD4-CCR5 complexes exhibit an epitope recognized by a Fab (X5) obtained by selection of a phage display library from a seropositive donor with a relatively high broadly neutralizing serum antibody titer against an immobilized form of the trimolecular complex. X5 bound with high (nM) affinity to a variety of Envs, including primary isolates from different clades and Envs with deleted variable loops (V1, -2, -3). Its binding was significantly increased by CD4 and slightly enhanced by CCR5. X5 inhibited infection of peripheral blood mononuclear cells by a selection of representative HIV-1 primary isolates from clades A, B, C, D, E, F, and G with an efficiency comparable to that of the broadly neutralizing antibody IgG1 b12. Furthermore, X5 inhibited cell fusion mediated by Envs from R5, X4, and R5X4 viruses. Of the five broadly cross-reactive HIV-1-neutralizing human monoclonal antibodies known to date, X5 is the only one that exhibits increased binding to gp120 complexed with receptors. These findings suggest that X5 could possibly be used as entry inhibitor alone or in combination with other antiretroviral drugs for the treatment of HIV-1-infected individuals, provide evidence for the existence of conserved receptor-inducible gp120 epitopes that can serve as targets for potent broadly cross-reactive neutralizing antibodies in HIV-1-infected patients, and have important conceptual and practical implications for the development of vaccines and inhibitors.


Pilot study on a new endoscopic platform for colorectal endoscopic submucosal dissection.
The endoscopic submucosal dissection (ESD) is a technically demanding and time-consuming procedure, with an increased risk of adverse events compared to standard endoscopic resection techniques. The main difficulties are related to the instability of the operating field and to the loss of traction. We aimed to evaluate in a pilot trial a new endoscopic platform [tissue retractor system (TRS); ORISE, Boston scientific Co., Marlborough, MA, USA], designed to stabilize the intraluminal space, and to provide tissue retraction and counter traction. We prospectively enrolled all consecutive patients who underwent an ESD for sigmoid/rectal lesions. The primary outcome was the rate of technical feasibility. Further technical aspects such as en-bloc and R0 resection rate, number of graspers used, circumferential incision time, TRS assemblage time, submucosal dissection time, and submucosal dissection speed were provided. Clinical outcomes (recurrence rate and adverse events) were recorded as well. In all, 10 patients (M/F 4/6, age: 70.4 ± 11.0 years old) were enrolled. Eight out of 10 lesions were located in the rectum. Average lesion size was 31.2 ± 2.7 mm, and mean lesion area was 1628.88 ± 205.3 mm2. The two sigmoid lesions were removed through standard ESD, because the platform assemblage failed after several attempts. All rectal lesions were removed in an en-bloc fashion. R0 resection was achieved in 7/8 (87.5%) patients in an average procedure time of 60.5 ± 23.3 min. None of the patients developed neither intraprocedural nor postprocedural adverse events. TRS-assisted ESD is a feasible option when used in the rectum, with promising result in terms of efficacy and safety outcomes. Nevertheless, our pilot study underlines few technical limitations of the present platform that need to be overcome before the system could be widely and routinely used.


Beyond organoids: In vitro vasculogenesis and angiogenesis using cells from mammals and zebrafish.
The ability to culture complex organs is currently an important goal in biomedical research. It is possible to grow organoids (3D organ-like structures) in vitro; however, a major limitation of organoids, and other 3D culture systems, is the lack of a vascular network. Protocols developed for establishing in vitro vascular networks typically use human or rodent cells. A major technical challenge is the culture of functional (perfused) networks. In this rapidly advancing field, some microfluidic devices are now getting close to the goal of an artificially perfused vascular network. Another development is the emergence of the zebrafish as a complementary model to mammals. In this review, we discuss the culture of endothelial cells and vascular networks from mammalian cells, and examine the prospects for using zebrafish cells for this objective. We also look into the future and consider how vascular networks in vitro might be successfully perfused using microfluidic technology.


Escobar Syndrome-An Multidisciplinary Approach for an Excellent Outcome With 3 Years of Follow-Up.
This case report intends to provide the facial characteristics of Escobar syndrome and to describe the orthodontic treatment of a 12-year-old female patient diagnosed with it. Escobar syndrome, a variant of the multiple pterygium syndrome, is a rare disorder with many systemic, facial, and oral manifestations.The patient presented with mixed dentition, severe dolichofacial pattern, increased lower facial height, convex profile, severe anterior open bite, maxillary hypoplasia, and mandibular retrognatism. The multidisciplinary approach included soft cleft palate repair, orthodontic treatment, orthognathic surgery, restorative cosmetic dentistry, speech therapy, and physiotherapy. Despite the limitations imposed by the syndrome, this report illustrates how the multidisciplinary treatment approach aided in the correction of occlusal function and facial esthetics and improvement in the quality of life of the patient with Escobar syndrome.


Zero-voltage conductance of short gold nanowires.
Using the Landauer formula, the conductance of short gold wires is studied. The required electronic structure calculations are performed with a self-consistent tight-binding method. We consider gold wires of single-atom diameter with a variable number (N=1, em leader,5) of atoms. Depending on N, we find considerable conductance variations with one conductance quantum being the upper limit. The results are confirmed by means of Friedel's sum rule. Tip-shaped clusters are used to provide the contact-wire interfaces and the relation between various tip structures and the conductance is discussed. Our predictions about the conductance variations agree qualitatively with new experimental results.


An efficient ECG baseline removal filter based on frequency response masking technique for wearable applications.
This paper presents a computationally efficient FIR (finite impulse response) filter for ECG (electrocardiogram) baseline wander removal. The proposed filter is based on frequency-response masking (FRM) technique, which reduces the number of multiplications by 90% compared to the conventional FIR filter. The filter specifications are optimized to obtain the highest SNR (signal-to-noise ratio) while minimizing the number of filter coefficients. The SNR performance of the proposed filter is evaluated using ECG signals from MIT-BIH Arrhythmia Database with added baseline noises from MIT-BIH Noise Stress Test Database. Simulations show that the FRM filter is capable of removing most of baseline wander while preserves ECG signal.


Nikkomycin biosynthesis: formation of a 4-electron oxidation product during turnover of NikD with its physiological substrate.
Nikkomycins are peptidyl nucleoside antibiotics that act as therapeutic antifungal agents in humans and easily degraded insecticides in agriculture. The nikkomycin peptidyl moiety contains a pyridyl residue derived from L-lysine. The first step in peptidyl biosynthesis is an aminotransferase-catalyzed reaction that converts L-lysine to Delta(1)- or Delta(2)-piperideine-2-carboxylate (P2C). Spectral, chromatographic, and kinetic analyses show that the aerobic reaction of nikD with P2C results in the stoichiometric formation of picolinate, accompanied by the reduction of 2 mol of oxygen to hydrogen peroxide. A high resolution HPLC method, capable of separating picolinate, nicotinate and isonicotinate, was developed and used in product identification. NikD contains 1 mol of covalently bound FAD and exists as a monomer in solution. Reductive and oxidative titrations with dithionite and potassium ferricyanide, respectively, show that FAD is the only redox-active group in nikD. Anaerobic reaction of nikD with 1 mol of P2C results in immediate reduction of enzyme-bound FAD. Because nikD is an obligate 2-electron acceptor, it is proposed that the observed 4-electron oxidation of P2C to picolinate occurs via a mechanism involving two successive nikD-catalyzed 2-electron oxidation steps. In addition to nikkomycins, a nikD-like reaction is implicated in the biosynthesis of an L-lysine-derived pyridyl moiety found in streptogramin group B antibiotics that are used as part of a last resort treatment for severe infections due to gram positive bacteria.


[Icodextrin improve angiogenesis of peritoneal membrane in continuous ambulatory peritoneal dialysis patients].
To observe the effect of icodextrin on peritoneal membrane angiogenesis in continuous ambulatory peritoneal dialysis (CAPD) patients. This was a randomized double-blind perspective study of CAPD patients at our center between January 2006 to December 2006. The patients were randomized to receive either 7.5% icodextrin (ICO, n = 27) or glucose (GLU, n = 27) solution at night for 4 weeks. Peritoneal membrane function was defined as dialysate dwell for 4 hours to plasma ratio of creatinine (4 h D/Pcr) at baseline. Ultrafiltration volume, creatinine clearance (Ccr), VEGF and IL-6 in peritoneal effluent during the long night dwell (UF) dialysate were measured at baseline and after 4 weeks. The VEGF appearance was used to adjust the influences of dwell time and ultrafiltration volume. A total of 54 patients were enrolled. The baseline conditions showed no difference between the groups. After 2 and 4 weeks of therapy, both net UF and peritoneal creatinine clearance of long dwell were significantly higher in the ICO group than the GLU group. VEGF in night dwell PD solution was positively correlated with D/PCr (r = 0.68, P < 0.01)and negatively correlated to 4 hour ultrafiltration volume (r = -0.51, P < 0.01). The VEGF appearance was comparable between two groups at baseline. After a follow-up of 4 weeks, the VEGF appearance had an increasing tendency in the GLU group and a decreasing tendency in the ICO group but there was no significant difference. The ΔVEGF appearance (VEGF appearance in 4 week-VEGF appearance at baseline) was different between the GLU and ICO groups (9.5 ± 20.2 vs -13.4 ± 26.1, P < 0.01). IL-6 in night dwell dialysate had no difference between two groups. As compared with glucose-based solution, 7.5% icodextrin significantly decreases the local VEGF level in dialysate.


A Novel Pediatric Emergency Department Intervention to Improve Adolescent Sexual Health Care.
The aim of this study was to evaluate a novel educational intervention for physician trainees to improve sexual health care provision, including condom distribution, in the pediatric emergency department. Resident physicians and medical students in an urban pediatric emergency department viewed an evidence-based educational video on sexual health care provision. It featured role-plays and a description of the condom distribution process, and targeted trainees who provide health care to patients aged 14 years or more with potential genitourinary complaints. Trainees completed pre- and postintervention surveys to assess attitudes, motivation, and confidence for 4 recommended practices (Likert scale, 1 = not at all to 4 = extremely). We used Wilcoxon signed rank tests to assess differences in paired responses to motivation and confidence statements. A subset of 33 trainees completed a brief survey to assess condom distribution during emergency department clinical encounters. Of 56 trainees, 51 (91%) participated: 53% female, 58% from pediatrics. At baseline, participants reported high levels of confidence and motivation to provide sexual health care. Postintervention, there were significant increases in the proportion of participants who reported greater motivation and confidence to (1) ask a parent to step out of the room, (2) obtain sexual history, (3) discuss condom use, and (4) offer condoms (all P < 0.05). Postintervention, fewer participants "agreed/strongly agreed" that there is inadequate time to obtain sexual histories (22% vs 45%; P < 0.05). Most (60%) sexually active patients accepted condoms during clinical care. In this pediatric emergency department, a low-cost intervention showed promise to improve trainee attitudes, motivation, and confidence toward adolescent sexual health care provision. These data may inform strategies to improve access to care for this population.


Integrative comparative analyses of transcript and metabolite profiles from pepper and tomato ripening and development stages uncovers species-specific patterns of network regulatory behavior.
Integrative comparative analyses of transcript and metabolite levels from climacteric and nonclimacteric fruits can be employed to unravel the similarities and differences of the underlying regulatory processes. To this end, we conducted combined gas chromatography-mass spectrometry and heterologous microarray hybridization assays in tomato (Solanum lycopersicum; climacteric) and pepper (Capsicum chilense; nonclimacteric) fruits across development and ripening. Computational methods from multivariate and network-based analyses successfully revealed the difference between the covariance structures of the integrated data sets. Moreover, our results suggest that both fruits have similar ethylene-mediated signaling components; however, their regulation is different and may reflect altered ethylene sensitivity or regulators other than ethylene in pepper. Genes involved in ethylene biosynthesis were not induced in pepper fruits. Nevertheless, genes downstream of ethylene perception such as cell wall metabolism genes, carotenoid biosynthesis genes, and the never-ripe receptor were clearly induced in pepper as in tomato fruit. While signaling sensitivity or actual signals may differ between climacteric and nonclimacteric fruit, the evidence described here suggests that activation of a common set of ripening genes influences metabolic traits. Also, a coordinate regulation of transcripts and the accumulation of key organic acids, including malate, citrate, dehydroascorbate, and threonate, in pepper fruit were observed. Therefore, the integrated analysis allows us to uncover additional information for the comprehensive understanding of biological events relevant to metabolic regulation during climacteric and nonclimacteric fruit development.


Access to preventive care services and stage at diagnosis in head and neck cancer.
Decreased access to preventive care services has been proposed as a mechanism for the association between low socioeconomic status (SES) and advanced stage at diagnosis in patients with head and neck squamous cell carcinoma (HNSCC). Retrospective analysis of patients diagnosed with HNSCC in North Carolina between 2002 and 2006. A total of 1108 patients with HNSCC were included in the study. In the multivariable analysis, use of annual routine dental services (OR 0.7, 95% CI 0.5-0.9) and colonoscopy in the past 10 years (OR 0.7, 95% CI 0.5-0.9) were associated with lower odds of advanced T stage at diagnosis. Having no insurance (OR 1.8, 95% CI 1.1-2.9), an income <$20 000 (OR 1.6 95% CI 1.03-2.6), and >10 pack-years tobacco use (OR 1.5, 95% CI 1.04-2.2) were associated with advanced T stage at diagnosis. Use of preventive care services and SES independently predict stage at diagnosis in HNSCC.


A Patient with COVID-19 Disease in a Referral Hospital in Iran: A Typical Case.
After the initial outbreak of the new Coronavirus in Wuhan at the end of December 2019, many new cases were reported in other provinces of China and also many other countries over the world, including South Korea, Italy, Iran, Japan, and 68 other countries. We present a case report of a 61-year-old woman with a history of diabetes mellitus who was referred to the emergency department of a referral hospital in Tehran, Iran. The patient presented with fever, chills, and myalgia within three days. Laboratory analysis showed increased levels of erythrocyte sedimentation rate (ESR), and mild leukopenia. SARS-CoV-2 PCR test -under the Iran Ministry of Health and Medical Education (MoH&ME) guidelines- was conducted and the result was positive. The chest X-ray showed bilateral ground-glass opacity. O2 saturation was 87% (without O2 therapy). The patient was hospitalized and treated with Oseltamivir 75 mg every 12 hours, Lopinavir/Ritonavir (Kaletra) 400/100 mg every 12 hours and hydroxychloroquine 400 mg stat. The patient's last O2 saturation measured was 93% and she had no fever on the 10th day of hospitalization. Therefore, she was discharged from hospital and quarantined at home according to the Iran Ministry of Health protocol.


Dynamic scaling of fronts in the quantum XX chain.
The dynamics of the transverse magnetization in the zero-temperature XX chain is studied with emphasis on fronts emerging from steplike initial magnetization profiles. The fronts move with fixed velocity and display a staircase like internal structure whose dynamic scaling is explored both analytically and numerically. The front region is found to spread with time subdiffusively with the height and the width of the staircase steps scaling as t(-1/3) and t(1/3), respectively. The areas under the steps are independent of time; thus the magnetization relaxes in quantized "steps" of spin flips.


Bleaching and mortality of reef organisms during a warming event in 1995 on the Caribbean coast of Costa Rica.
Coral reefs at the Caribbean coast of Costa Rica were affected during a bleaching event associated with the 1995 warming of the Western Caribbean. During doldrum weather in late August 1995, reef organisms at Parque Nacional Cahuita were 62% and 7.4% bleached and dead respectively, whilst 67.6% bleached and 8.2% died in the Refugio Nacional de Vida Silvestre Gandoca-Manzanillo. However, Cahuita had the highest mean number of bleached (257 +/- 51.1) and dead (30.5 +/- 5.6) colonies in the surveyed transects, and bleaching was observed down to a depth of 20 m. The most affected species (>10% of dead colonies) were the hydrocoral Millepora complanata and the scleractinian corals Montastraea spp. at Cahuita, and Porites furcata, Porites porites and M. complanata at Gandoca-Manzanillo. Mean seawater temperature was between 30.5 and 31.1 degrees C (0-18 m depth) during four days of observation at the end of August 1995. Coral reefs of the Costa Rican Caribbean coast have shown a rapid decline during the last 20 years due to natural and anthropogenic disturbances. The effect of the 1995 warming added more pressure to the already deteriorated reefs.


Characterization of activin A-, activin AB- and activin B-responding cells by their responses to hypothalamic releasing hormones.
Activin A-, AB- and B-responding cells were characterized by their responsiveness in cytosolic free calcium ([Ca2+])i) to four hypothalamic releasing hormones, CRH, GHRH, TRH and GnRH. First, rat pituitary cells responding to activin A, AB and B in [Ca2+]i were determined in a mixed population of pituitary cells. The populations of the activin A-, AB-, and B-responding cells were 13.9%, 9.3% and 13.2%, respectively. Overlapping of response among each population of activin- responding cells was present in some of the cells. The cells responding to activin A, AB, and B were then characterized by their responses to CRH, GHRH, TRH and GnRH. Most of the cells responding to activin A, AB, and B also responded to GHRH or TRH. These results reveal that there are distinct differences among each population of activin A-, AB- and B-responding cells and that there is still functional overlapping of responsiveness among these populations. The characterization of activin-responding cells suggests involvement of somatotropes and lactotropes in activin-induced biological events in the pituitary.


Chromatin-remodeling SWI/SNF complex regulates coenzyme Q6 synthesis and a metabolic shift to respiration in yeast.
Despite its relatively streamlined genome, there are many important examples of regulated RNA splicing in Saccharomyces cerevisiae Here, we report a role for the chromatin remodeler SWI/SNF in respiration, partially via the regulation of splicing. We find that a nutrient-dependent decrease in Snf2 leads to an increase in splicing of the PTC7 transcript. The spliced PTC7 transcript encodes a mitochondrial phosphatase regulator of biosynthesis of coenzyme Q6 (ubiquinone or CoQ6) and a mitochondrial redox-active lipid essential for electron and proton transport in respiration. Increased splicing of PTC7 increases CoQ6 levels. The increase in PTC7 splicing occurs at least in part due to down-regulation of ribosomal protein gene expression, leading to the redistribution of spliceosomes from this abundant class of intron-containing RNAs to otherwise poorly spliced transcripts. In contrast, a protein encoded by the nonspliced isoform of PTC7 represses CoQ6 biosynthesis. Taken together, these findings uncover a link between Snf2 expression and the splicing of PTC7 and establish a previously unknown role for the SWI/SNF complex in the transition of yeast cells from fermentative to respiratory modes of metabolism.


Physical activity in patients who are severely mentally ill: feasibility of assessment for clinical and research applications.
Few studies have examined physical activity in patients who are severely mentally ill. We assessed feasibility and validity of using standardized self-report and objective measures of physical activity in 20 community-dwelling veteran patients, most with psychotic disorders and substance abuse in remission. Test-retest reliability of a past week physical activity survey and the Community Healthy Activities Model Program for Seniors interview were evaluated with repeated interviews. RT3 accelerometer data provided objective physical activity data. Test-retest reliability and validity correlations for the self-report instruments were similar in magnitude to those reported for nonclinical adult samples. Some activity measures were correlated with cognitive status and quality of life. Results indicate that self-reported physical activity can provide valid information for clinical and research applications in mental health settings. Correlations between physical activity measures and psychiatric symptoms suggested interesting patterns for future study.


Formation of supramolecular permethrin/beta-cyclodextrin nanorods.
Molecular dynamics simulations along with scanning tunneling microscopy (STM) imaging demonstrate the formation of a novel type of nanorods, with a stable [permethrin(beta-CD)(2)](n) structure in which the host:guest ratio is 2:1 and n=21-27 giving a length of approximately 30.0-38.5 nm and an average diameter of approximately 1.5 nm, self-assembled from an inclusion complex composed of permethrin and biocompatible beta-cyclodextrin.


Effect of indomethacin on cerebral blood flow velocities in very low birth weight neonates with a patent ductus arteriosus.
The effect of repeated doses of indomethacin on mean peak velocity (MPV) and time-averaged mean velocity in the middle cerebral artery was assessed in 10 ventilated neonates with a patent ductus arteriosus using colour/duplex Doppler technique prior to, and 10, 30, and 120 min after the first and the third dose. Velocities were significantly reduced up to 120 min after the first dose. The third dose resulted in a significant reduction in MPV at 10 and 30 min following treatment. This reduction was half of that observed after the first dose. Systemic blood pressure (BP) and heart rate did not change significantly after each separate dose. However, by the third dose, mean and diastolic BP were significantly increased from pretreatment levels. The attenuated response of cerebral blood flow (CBF) velocities to the third dose of indomethacin compared with the first dose is probably related to altered haemodynamics. Indomethacin should be used cautiously in infants with other conditions which are known to decrease CBF such as hypotension, hypocarbia and polycythaemia.


Regulating the Coordination Environment of Single-Atom Catalysts Anchored on Thiophene Linked Porphyrin for an Efficient Nitrogen Reduction Reaction.
The electrochemical nitrogen reduction reaction (NRR) offers a promising strategy to resolve high energy consumption in the nitrogen industry. Recently, the regulation of the electronic structure of single-atom catalysts (SACs) by adjusting their coordination environment has emerged as a rather promising strategy to further enhance their electrocatalytic activity. Herein, we design novel SACs supported by thiophene-linked porphyrin (TM-N4/TP and TM-N4-xBx/TP, where TM = Sc to Au) as potential NRR catalysts using density functional theory calculations. Among these catalysts, TM-N4/TP (TM = Ti, Nb, Mo, Ta, W, and Re) and TM-N4/TP with a water bilayer (TM = Nb, Mo, W, and Re) show excellent activity (low limiting potential) but low selectivity. Encouragingly, we find that Mo-N3B/TP, Mo-N2B2-2/TP, W-N3B/TP, W-N2B2-2/TP, Re-N3B/TP, Re-N2B2-2/TP, and Re-N2B2-1/TP serve as the most efficient NRR electrocatalysts, as they present stability, superior activity, better selectivity with low limiting potentials (-0.18 ∼ -0.90 V), and high Faradaic efficiencies (>99.80%). Based on microkinetic modeling, kinetic analysis of the NRR is performed and shows that the Re-N2B2-1/TP catalyst is more efficient for NH3 formation. Additionally, multiple-level descriptors provide insight into the origin of NRR activity and enable fast prescreening among numerous candidates. This work provides a new perspective to design highly efficient catalysts for the NRR under ambient conditions.


Factors affecting attitudes toward juvenile sex offenders.
This study investigated attitudes toward juvenile sex offenders and factors influencing those attitudes. Additionally, the influences of perpetrator characteristics such as age, gender, and ethnicity on societal attitudes towards intervention requirements were also investigated. Overall, attitudes toward juvenile sex offenders and their treatment amenability were negative. No differences in attitudes toward juvenile sex offenders were found between those who had been victims of sexual abuse and those that had not. Sex offenses committed by juvenile female sex offenders were viewed to be more serious and require more intervention than those committed by juvenile male sex offenders.


Rumen Microbiota Distribution Analyzed by High-Throughput Sequencing After Oral Doxycycline Administration in Beef Cattle.
The beef cattle rumen is a heterogenous microbial ecosystem that is necessary for the host to digest food and support growth. The importance of the rumen microbiota (RM) is also widely recognized for its critical roles in metabolism and immunity. The level of health is indicated by a dynamic RM distribution. We performed high-throughput sequencing of the bacterial 16S rRNA gene to compare microbial populations between rumens in beef cattle with or without doxycycline treatment to assess dynamic microbiotic shifts following antibiotic administration. The results of the operational taxonomic unit analysis and alpha and beta diversity calculations showed that doxycycline-treated beef cattle had lower species richness and bacterial diversity than those without doxycycline. Bacteroidetes was the predominant phylum in rumen samples without doxycycline, while Proteobacteria was the governing phylum in the presence of doxycycline. On the family level, the top three predominant populations in group qlqlwy (not treated with doxycycline) were Prevotellaceae, Lachnospiraceae, and Ruminococcaceae, compared to Xanthomonadaceae, Prevotellaceae, and Rikenellaceae in group qlhlwy (treated with doxycycline). At the genus level, the top predominant population in group qlqlwy was unidentified_Prevotellaceae. However, in group qlhlwy, the top predominant population was Stenotrophomonas. The results revealed significant RM differences in beef cattle with or without doxycycline. Oral doxycycline may induce RM composition differences, and bacterial richness may also influence corresponding changes that could guide antibiotic use in adult ruminants. This study is the first to assess microbiota distribution in beef cattle rumen after doxycycline administration.


Nifedipine versus carvedilol in the treatment of de novo arterial hypertension after liver transplantation: results of a controlled clinical trial.
The aim of this study was to compare nifedipine and carvedilol in the treatment of de novo arterial hypertension after orthotopic liver transplantation (OLT). The study included 50 patients who developed arterial hypertension after OLT. Twenty-five patients received nifedipine (group A), and 25 received carvedilol (group B). Patients were defined as intolerant to nifedipine or carvedilol if severe adverse effects developed. These patients stopped the first drug and were switched to the other one. Patients were defined as full responders to monotherapy if there was normalization of blood pressure, and they were defined as partial responders by the need to add a second antihypertensive drug, ramipril. The 2 groups of patients were similar for baseline conditions. At the end of the study, patients intolerant to monotherapy were 48% of group A and 12.5% of group B (P < 0.01). Full responders were 20% of group A and 33.33% of group B (P < 0.01). Partial responders were 22% of group A and 54.1% of group B (P < 0.01). The addition of ramipril normalized blood pressure in 19% of partial responders to monotherapy (75% in partial responders to nifedipine and 30% in partial responders to carvedilol, P < 0.01). In responders to either monotherapy or combined therapy, there was a significant improvement of renal function. In responders to carvedilol, but not in responders to nifedipine, the daily dose of tacrolimus at 1 year should be reduced to 50% compared to the baseline dose to maintain the blood trough level in the therapeutic range.


Validation of the National Institutes of Health Stroke Scale, modified Rankin Scale and Barthel Index in Brazil: the role of cultural adaptation and structured interviewing.
We aimed to validate three widely used scales in stroke research in a multiethnic Brazilian population. The National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI) were translated, culturally adapted and applied by two independent investigators. The mRS was applied with or without a previously validated structured interview. Interobserver agreement (kappa statistics) and intraclass correlation coefficients were calculated. 84 patients underwent mRS (56 with and 28 without a structured interview), 57 BI and 62 NIHSS scoring. Intraclass correlation coefficient was 0.902 for NIHSS and 0.967 for BI. For BI, interobserver agreement was good (kappa = 0.70). For mRS, the structured interview improved interobserver agreement (kappa = 0.34 without a structured interview; 0.75 with a structured interview). The NIHSS, BI and mRS show good validity when translated and culturally adapted. Using a structured interview for the mRS improves interobserver concordance rates.


Simple computational technique to quantify nuclear shape asymmetry.
The nucleus of an eukaryotic cell is a membrane-bound organelle containing a major part of the cellular genome. Nuclear shape is controlled by forces generated in the cytoskeleton, nuclear envelope and matrix of the nucleus and may change when the balance of these forces is disturbed. In certain cases, such changes may be indicative of cell pathology. Nuclear shape feature is being commonly addressed in both experimental research and diagnostics; nevertheless its symmetry-related aspects receive little attention. This article introduces a technique allowing to estimate nuclear shape asymmetry in digital images captured from cyto- or histological preparations. Implemented in a software package, this technique quantifies the asymmetry using two scenarios. The first one presumes the identification of nuclear pixels laying outside the largest inscribed circle. According to the second scenario, the algorithm searches for nuclear pixels lacking pixel-partners symmetric with respect to the nuclear area's centroid. In both cases, the proportion of "asymmetric" pixels is used to estimate the feature of interest. The technique was validated on images of cell nuclei having distinctive shape phenotypes. A conclusion was made that shape asymmetry feature may be useful accessory to the toolbox of nuclear morphometry.


Anticancer effects of Ac‑Phe‑Lys‑PABC‑doxorubicin via mitochondria‑centered apoptosis involving reactive oxidative stress and the ERK1/2 signaling pathway in MGC‑803 cells.
Ac‑Phe‑Lys‑PABC‑DOX (PDOX) is a smart doxorubicin (DOX) prodrug designed to decrease toxicities while maintaining the potent anticancer effects of DOX. The present study aimed to elucidate the molecular mechanisms of action of PDOX using MGC‑803 gastric cancer cells as a model. The cells were treated with both PDOX and DOX, and cytotoxicities, cell cycle analysis, reactive oxygen species (ROS) generation, mitochondrial damage and ERK1/2 signaling pathway alterations were studied. Abundant cathepsin B expression was observed in the MGC‑803 cells, and treatment with PDOX and DOX triggered dose‑dependent cytotoxicity and resulted in a significant reduction in cell viability. IC50 of PDOX and DOX was 14.9 and 4.9 µM, respectively. Both PDOX and DOX significantly decreased p‑ERK1/2, increased ROS generation, reduced mitochondrial membrane potential, caused mitochondrial swelling and arrested the cell cycle at the G2/S phase, and these effects were more pronounced for PDOX than for DOX. PDOX and DOX have different mechanisms of action, particularly the mitochondria‑centered intrinsic apoptosis involving reactive oxidative stress and the ERK1/2 signaling pathway.


Clinical potential of blood substitutes or oxygen therapeutics during cardiac surgery.
Several complications and unforeseen adverse side effects have colluded to keep commercially available blood substitutes or oxygen therapeutic agents tantalizingly "just out of reach." Because the three classes of agents under development have different oxygen-delivery mechanisms and side-effect profiles, each can be expected to have its own unique clinical applications, particularly in the cardiac surgery population. The fact that South Africa recently approved one HBOC for use as a transfusion alternative in patients with chronic anemia indicates that initial clinical use is near for a number of these agents. It is to be hoped that they will be used for several applications rather than just for a "transfusion alternative." Despite some frustrating limitations, all of these agents are antigen and pathogen free, have an acceptable side-effect profile, and have a long shelf life. Increasing volunteer-blood-donor shortages, coupled with increasing blood-transfusion needs, and expanding human immunodeficiency virus and hepatitis B and C epidemics, continue to fuel the demand for further development of these products. Transfusion alternatives will eventually become commercially available--the question is "when," not "if." Equally important, these agents' potential for serving as effective oxygen-delivery agents to ischemic tissues heralds an entirely new field of clinical investigation.


Does circumcision alter the periurethral bacterial flora?
A prospective study of 25 boys who underwent circumcision for medical reason was performed. Specimens of periurethral bacterial flora were taken before operation as well as 3 weeks after surgery, so that each boy acted as his own control. Before circumcision, 13 (52%) harboured uropathogenic organisms (Escherichia coli and other coliforms, Enterococcus spp, Proteus spp, Pseudomonas spp, and Klebsiella spp); after circumcision, none of the boys had uropathogens, the only organisms cultured from the periurethral region being skin commensals. We postulate that circumcision converts a 'cul-de-sac' that is a reservoir of organisms capable of causing ascending urinary tract infection into a surface colonised by natural skin organisms. This study provides circumstantial evidence supporting the idea that circumcision in well-selected patients may confer protection from urine infection.


The state of American health coverage: the 2022 elections and the Affordable Care Act.
The Affordable Care Act of 2010 (ACA) was the most significant policy breakthrough to expand health insurance coverage in the USA in 45 years. Culminating a decade-long effort by Republicans to repeal and undermine the ACA, the Trump administration launched a panoply of executive initiatives to sabotage the law. Benefitting from Democratic control of both the House and Senate during its first 2 years, the Biden administration through legislative and executive initiatives made substantial headway in reversing Trump's sabotage and further reinvigorating the ACA. The 2022 elections witnessed a shift in the partisan milieu. Republicans gained control of the House of Representatives; Democrats scored modest gains in state elections. Emphasising two pivotal features of American governance - federalism and the outsized role of the courts - this essay examines the implications of this new partisan context for Biden's efforts to bolster ACA durability prior to the 2024 presidential election.


The Language of Scholarship: How to Rapidly Locate and Avoid Common APA Errors.
This article is relevant for nurses and nursing students who are writing scholarly documents for work, school, or publication and who have a basic understanding of American Psychological Association (APA) style. Common APA errors on the reference list and in citations within the text are reviewed. Methods to quickly find and reduce those errors are shared.


[Study of photocatalytic performance of TiO2 membrane for oleic acid by FTIR-ATR technique].
The TiO2 membranes were prepared on glass, ceramic tile and aluminum pieces by Sol-Gel and PVD methods. A fast and exact evaluation on the photocatalytic self-cleaning performance of the membrane materials was achieved by FTIR-ATR technique using oleic acid which was laid on the surface of the membrane. The hydrophilic property of the samples was also determined by the contact angle with water. The results showed that both the TiO2 membrane prepared on glass by the Sol-Gel and PVD methods displayed good photo-induced hydrophilic property and degradation activity of oleic acid, and no difference in hydrophilic property, but the former was a little superior to the latter in photocatalytic activity. The photocatalytic conversion of oleic acid on the TiO2/glass, TiO2/ceramic tile and TiO2 aluminum piece were 92%, 85% and 46%, respectively after illumination 3.5 h, showing a distinct effect of support material property on TiO2 photocatalytic performance. The results suggested that the photocatalytic activity of TiO2 membrane coated on insulator support was higher than that coated on conductor support.


Laser-induced microjet injection into preablated skin for more effective transdermal drug delivery.
A breakthrough in the efficient transdermal delivery of drug via the laser-driven microjet is reported. A single source of laser beam is split into two: one beam ablates a targeted spot on a skin and another beam drives the injector for fast microjet ejection into a preablated spot. This combined ablation and microjet injection scheme using a beam splitter utilizes laser energy sharing between generation of the microhole via ablation and the microjet which is generated using the Er:YAG laser beam at a 2940-nm wavelength and pulse duration. A careful analysis of the injection mechanism is carried out by studying the response of the elastic membrane that separates a driving water unit for bubble expansion from a drug unit for a microjet ejection. The efficiency of the present delivery scheme is evaluated by the abdominal porcine skin test using the fluorescein isothiocyanate staining and the confocal microscopy for quantitative delivery confirmation. The depth of penetration and the injected volume of the drug are also confirmed by polyacrylamide gel tests.


Differences in Power Acquisition Between Only and Non-only Children: The Effects of Cooperative Orientation, Competitive Orientation, and Dependency on Parents.
Drawing upon a developmental perspective, we investigated the differences in power acquisition (i.e., rank at work and leader role occupancy in university) between only and non-only children as well as the mediating role of cooperative and competitive orientations and the moderating role of dependency on parents. To test our hypotheses, we conducted two field studies in 155 part-time Master of Business Administration (MBA) students (Study 1) and 375 senior students (Study 2). Results showed that: (1) non-only children were more likely to achieve higher rank at work than only children; (2) only children were less likely than non-only children to acquire power in organizations because they scored lower in cooperative orientation; however, the mediating effect of competitive orientation was not significant; (3) the difference in cooperative orientation between only and non-only children was smaller when dependency on parents was high, whereas it became larger when dependency on parents was low. Our research contributes to the understanding of how family structure influences individual power acquisition.


Donor lymphocyte infusions (DLI) in patients with chronic myeloid leukemia following allogeneic bone marrow transplantation.
Donor lymphocyte infusions (DLI) were given between June 1990 and March 1996 to 18 patients with chronic myeloid leukemia (CML) for the treatment of cytogenetic (n = 6) or hematologic relapse (n = 12) following an allogeneic bone marrow transplant (BMT). Patients were divided in two groups: patients in group A (n = 8) received a large dose of donor lymphocytes (> or = 1 x 10(8)/kg), whereas patients in group B (n = 10) received escalating numbers of cells (2 x 10(5) up to 2 x 10(8)/kg). The median number of DLI in group A was 2 (range 1-3); the median number of infusions in group B was 7 (range 3-9). Acute GVHD occurred in 12 patients (grades I-III) and was a major cause of death in two. The risk of developing GVHD correlated with the number of cells infused: 37%, 14%, 5% and 0% for DLI with cells > or = 1 x 10(8), 2 x 10(7)/kg, 2 x 10(6)/kg, and 2 x 10(5)/kg, respectively (P = 0.01). Median transaminase levels were found to be significantly increased in patients with, as compared to patients without, acute GVHD (GPT 412 vs 28 IU/l; P = 0.03). Severe aplasia occurred in four and was a contributing cause of death in two patients. Overall, four patients died as a consequence of DLI and all received > 1 x 10(8)/kg cells: the actuarial risk was 38% in group A and 14% in group B (P = 0.1). There were 10 complete and three partial cytogenetic responses: the actuarial probability at 5 years of being Ph negative was 69%: it was 46% for group A and 85% for group B (P = 0.1). The longest patient is now 6 years post-DLI, Ph negative, BCR-ABL negative. The actuarial 3 year survival is 38% in group A and 86% in group B (P = 0.06). The study confirms that DLI post-BMT is not innocuous and that there is a definite long-lasting antileukemic effect in patients with CML. It also suggests that: (1) the risk of developing GVHD correlates with the number of infused cells; (2) that significant elevations of serum GPT levels are associated with GVHD; and (3) that the use of escalating doses of cells may allow the identification of side-effects and discontinuation of infusions before life-threatening GVHD has developed.


Akt-dependent proapoptotic effects of dietary restriction on late-stage management of a phosphatase and tensin homologue/tuberous sclerosis complex 2-deficient mouse astrocytoma.
Malignant astrocytomas exhibit constitutive Akt phosphorylation due to reduced phosphatase and tensin homologue (PTEN) tumor suppressor expression or to increased growth factor receptor tyrosine kinase activation. Many astrocytomas are also tuberous sclerosis complex 2 (TSC2) protein deficient and exhibit constitutive mammalian target of rapamycin (mTOR) activity. Astrocytomas harboring PTEN/Akt/TSC2 pathway mutations are dependent on glycolysis to satisfy their bioenergetic requirements. Therapies that disrupt energy homeostasis can potentially manage astrocytoma growth and progression. Although dietary restriction (DR) reduces glycolysis and manages early-stage astrocytoma growth, no prior studies have identified the mechanisms involved or determined if DR can also manage late-stage tumor growth. The effects of a late-onset intermittent DR feeding paradigm were examined in adult C57BL/6J mice bearing the syngeneic CT-2A malignant astrocytoma grown orthotopically or subcutaneously. In contrast to contralateral normal brain, CT-2A was PTEN/TSC2 protein deficient; exhibited constitutive Akt, mTOR, and BAD phosphorylation; and overexpressed insulin-like growth factor-I (IGF-I), IGF-I receptor, hypoxia-inducible transcription factor-1alpha (HIF-1alpha), type 1 glucose transporter protein (GLUT1), and pyruvate kinase. DR initiated 10 to 14 days after tumor implantation (late onset) reduced CT-2A growth, delayed malignant progression, and significantly extended survival. DR suppressed phosphorylation of Akt and BAD while reducing expression of IGF-I, HIF-1alpha, and GLUT1. DR also enhanced procaspase-9/procaspase-3 cleavage but had no effect mTOR phosphorylation. Our findings indicate that IGF-I/Akt signaling is associated with the antiapoptotic and glycolytic phenotype of the CT-2A astrocytoma and that DR targets this pathway. Moreover, PTEN/TSC2 deficiency may impair adaptation to the DR-induced disruption of energy homeostasis, thus enhancing apoptosis. Our findings highlight the efficacy of late-onset DR in managing astrocytoma growth and suggest that DR may be an effective broad-spectrum inhibitor of Akt signaling in PTEN/TSC2-deficient astrocytomas.


[Ethology of the pigeon (Columba livia)].
An ethometrical analysis of street pigeons showed that most social interactions under conditions of overpopulation are of an aggressive nature. Through various mechanisms this frequent aggressive behaviour leads to "slumlike" living conditions characterized by intraspecific stress. It is possible to characterize street pigeons in their urban environment by calculating the frequencies of the most important aggressive and sexually-motivated social interactions. Behavioral patterns adapted to their living conditions result in misbehaviour in an anthropogenous environment. A high population density in commercial pigeon units should therefore be avoided. It is also necessary to consider the typical disposition of a race for aggressive behaviour. The frequent aggressive interactions among street pigeons at their breeding lofts seem to play an important role as a density dependent regulator of population size.


An evaluation of circulating bovine viral diarrhea virus type 2 maternal antibody level and response to vaccination in Angus calves.
Vaccination against viruses has been shown to help prevent bovine respiratory disease in cattle. However, both passively acquired maternal antibody concentration and calf age have been shown to impact the ability of the immune system of a calf to respond to vaccination. The objectives of this study were to identify and evaluate environmental and management factors that affect 1) passively acquired bovine viral diarrhea virus (BVDV) type 2 antibody level, 2) decay rate of passively acquired BVDV type 2 antibody level, and 3) responses to BVDV type 2 vaccinations. A 2-shot modified live vaccine was administered to 1,004 Angus calves that were weaned at either the initial vaccination (n = 508) or the booster vaccination (n = 496). Calves weaned at the initial vaccination averaged 139 d whereas calves weaned at booster vaccination averaged 128 d of age. Bovine viral diarrhea virus type 2 antibodies were measured in 3 approximately 21-d intervals, serially collected serum samples to quantify antibody levels at initiation and end of vaccination protocol in addition to responses to initial, booster, and overall vaccination protocol. Amount of passively transferred antibody in the calf increased as dam age increased from 2 to 6 yr (P < 0.05) with no differences after dams reached 6 yr (P > 0.05). Calf age nested within birth year-season and dam age affected both initial and final antibody level, initial response, booster response, and overall antibody response to vaccination. The level of circulating, passively acquired maternal antibodies present at the time of vaccination had a significant (P < 0.05) negative effect on antibody responses to vaccination (initial response, booster response, and overall response). Calves that were weaned at the time of initial vaccination had significantly (P < 0.05) greater final antibody level, initial response, and overall response to vaccination than animals weaned at booster vaccination. In order for a calf to mount an overall antibody response to vaccination, maternal antibodies in circulation need to be less than 3.12 titers. However, the age at which a calf reached this antibody threshold was dependent on dam age. This information will help cattle managers and consultants design vaccination protocols to successfully mount an antibody response to vaccination.


Regional- and temporal-dependent changes in the differentiation of Olig2 progenitors in the forebrain, and the impact on astrocyte development in the dorsal pallium.
Olig2 is a basic helix-loop-helix transcription factor essential for oligodendrocyte and motoneuron development in the spinal cord. Olig2-positive (Olig2+) cells in the ventricular zone of the ventral telencephalon have been shown to differentiate into GABAergic and cholinergic neurons. However, the fate of Olig2 lineage cells in the postnatal forebrain has not been fully described and Olig2 may regulate the development of both astrocytes and oligodendrocytes. Here, we examined the fate of embryonic Olig2+ progenitors using a tamoxifen-inducible Cre/loxP system. Using long-term lineage tracing, Olig2+ cells in the early fetal stage primarily differentiated into GABAergic neurons in the adult telencephalon, while those in later stages gave rise to macroglial cells, both astrocytes and oligodendrocytes. Olig2+ progenitors in the diencephalon developed into oligodendrocytes, as observed in the spinal cord, and a fraction developed into glutamatergic neurons. Olig2 lineage oligodendrocytes tended to form clusters, probably due to local proliferation at the site of terminal differentiation. In spite of the abundance of Olig2 lineage GABAergic neurons in the normal neocortex, GABAergic neurons seemed to develop at normal density in the Olig2 deficient mouse. Thus, Olig2 is dispensable for GABAergic neuron specification. In contrast, at the late fetal stage in the Olig2 deficient mouse, astrocyte development was retarded in the dorsal neocortex, but not in the basal forebrain. Olig2 functions, therefore, in gliogenesis in the dorsal pallium. Short-term lineage tracing experiments revealed that the majority of late Olig2+ cells were not direct descendants of early Olig2+ progenitors in the fetal forebrain. These observations indicate that embryonic Olig2+ progenitor cells change their differentiative properties during development, and also that Olig2 plays a role in astrocyte development in a region-specific manner.


Interaction between oral contraceptive use and coagulation factor levels in deep venous thrombosis.
Deep venous thrombosis is a multicausal disease, i.e. more than one risk factor needs to be present to cause the disease. Oral contraceptive use increases the risk of venous thrombosis but since not all women using oral contraceptives develop thrombosis, the presence of additional risk factors in patients is likely. The aim of this study was to assess the joint effect of oral contraceptive use and the levels of procoagulant factors (F)(FII, FV, FVII, FVIII, FIX, FX, FXI, FXII, FXIII and fibrinogen). Data of premenopausal women were re-analyzed in the Leiden Thrombophilia Study. The highest relative risks were observed for the combination of oral contraceptive use and high levels (>90th percentile) of FII (Odds Ratio [OR]OC+FII 10.1; 95% confidence interval [CI] 3.5-29.0), FV (OROC+FV 12.6; 95% CI 3.8-41.5), and FXI (OROC+FXI 11.9; 95% CI 3.6-39.2) and low levels (< 10th percentile) of FXII (OROC+FXII 12.3; 95% CI 2.4-63.0). No interaction was observed between oral contraceptive use and high levels of the other coagulation factors, i.e. the joint effect of these risk factors did not exceed the sum of the separate effects. The results of this study indicate that the risk for the joint effects of oral contraceptive use and coagulation factor levels are minor compared with the joint effect of oral contraceptive use and the FV Leiden mutation (RR > 30).


Attenuation of nociceptin/orphanin FQ-induced signaling by N-methyl-D-aspartate in neuronal cells.
Acute incubation of NMDA with neuroblastoma x glioma hybrid (NG108-15) cells or neuroblastoma SK-N-SH cells produced significant attenuation of nociceptin/orphanin FQ (N/OFQ)-induced activation of G protein and inhibition of adenylyl cyclase. The attenuation of N/OFQ signaling by NMDA was dose-dependent, blockable by NMDA antagonists, and not observed in cells lacking NMDA receptors, indicating that the effect of NMDA is mediated by the NMDA receptor. Furthermore, NMDA antagonist pretreatment greatly attenuated N/OFQ-induced acute homologous desensitization of ORL1. Interestingly, the signaling induced by etorphine, an opioid agonist of wide spectrum, was sensitive to NMDA treatment in NG108-15 but insensitive in SK-N-SH cells, suggesting differential modulation of opioid signaling by NMDA. The attenuation effects of NMDA on mu opioid receptor-mediated signaling were also observed.


Dynamics of cell adhesion and motility in living cells is altered by a single amino acid change in E-cadherin fused to enhanced green fluorescent protein.
E-Cadherin regulates epithelial cell adhesion and is critical for the maintenance of tissue integrity. In sporadic diffuse-type gastric carcinoma, mutations of the E-cadherin gene are frequently observed that predominantly affect putative calcium binding motifs located in the linker region between the second and third extracellular domains. A single amino acid change (D370A) as found in a gastric carcinoma patient reduces cell adhesion and up-regulates cell motility. To study the effect of this mutation on the dynamics of cell adhesion and motility in living cells, enhanced green fluorescent protein (EGFP) was C-terminally fused to E-cadherin. The resulting mutant E-cadherin-EGFP fusion protein with a point mutation in exon 8 (p8-EcadEGFP) and a wild-type E-cadherin-EGFP fusion construct (wt-EcadEGFP) were expressed in human MDA-MB-435S cells. Fluorescent images were acquired by time-lapse laser scanning microscopy and E-cadherin was visualized during contact formation and in moving cells. Spatial and temporal localization of p8- and wt-EcadEGFP differed significantly. While wt-EcadEGFP was mainly localized at lateral membranes of contacting cells and formed E-cadherin puncta and plaques, p8-EcadEGFP-expressing cells frequently formed transient cell-cell contacts. During random cell migration, p8-EcadEGFP was found in lamellipodia. In contrast, wt-EcadEGFP localized at lateral cell-cell contact sites in low or non-motile cells. Inhibition of the epidermal growth factor (EGF) receptor, which plays a major role in lamellipodia formation and cell migration, reduced the motility of p8-EcadEGFP-expressing cells and caused lateral membrane staining of p8-EcadEGFP. Conversely, EGF induced cell motility and caused formation of lamellipodia that were E-cadherin positive. In conclusion, our data show that mutant E-cadherin significantly alters the dynamics of cell adhesion and motility in living cells and interferes with the formation of stable cell-cell contacts.


Changes in photo-aged human skin following topical application of all-trans retinoic acid.
Although topical applications of retinoids on rodents and humans have been shown to cause epidermal hyperplasia, a detailed study of the influence of retinoids on epidermal differentiation in vivo has not been performed. In order to assess the pharmacologic effects of chronic topical tretinoin application used to improve the appearance of patients with photoaged skin, cutaneous biopsies from 25 patients in a controlled clinical study were examined histologically and immunocytochemically. Chronic application of tretinoin causes epidermal thickening (25 of 25 samples), stratum granulosum thickening (15 of 25), parakeratosis (13 of 25), a marked increase in the number of cell layers expressing epidermal transglutaminase (13 of 25), and focal expression of two keratins, K6 (12 of 25) and K13 (8 of 25), not normally expressed in the epidermis. The morphologic changes correlated with immunohistochemical abnormalities; neither of these correlated with the subjective cosmetic response. Three major epidermal differentiation products, keratins K1, K10, and K14 were not altered, within the limits of the methods used. Thus, chronic topical tretinoin reprograms some, but not all, aspects of human epidermal differentiation in vivo.


Mycobacterium avium complex infection in kidney transplant patients.
Mycobacterium avium complex (MAC) infections have been reported rarely in renal transplant patients. Consequently the clinical course and optimal treatment of these patients are not well understood. We present 3 patients with MAC infections after receiving a renal transplant (2 with generalized and 1 with localized infection). All patients were treated with combination antibiotic therapy and reduction of immunosuppression. One patient experienced clinical control of disease but a mild cellular rejection that was successfully treated with high-dose corticosteroids. One patient died of disseminated MAC infection. The patient with localized infection died of unrelated causes. In summary, MAC infection, although rare in renal transplant patients, may respond to combination antimicrobial therapy and reduction of immunosuppression.


Diagnostic difficulties associated with phaeochromocytoma--4 case illustrations.
The diagnosis of phaeochromocytoma can be extremely difficult with 40%-76% of cases escaping diagnosis during life. Until recently, the only available biochemical test for the detection of phaeochromocytoma in Singapore has been the 24-hour urinary vanillyl mandelic acid (VMA). Urinary VMA has been reported to have a high specificity (85%-100%) but variable sensitivity (28%-90%) in the diagnosis of this disease. In 1993, high performance liquid chromatography (HPLC) assays for the measurement of urinary catecholamines and metanephrines were introduced at the Singapore General Hospital. Since 1993, 4 cases of phaeochromocytoma have been detected at our institution. We report here, the diverse clinical presentations of these patients. The urinary-free catecholamine and catecholamine metabolite levels of these patients were compared with corresponding levels from 12 non-phaeochromocytoma patients. Using the reference value of 65.6 mumol/day, we found the urinary VMA to be a highly sensitive (100%) test with a specificity of only 31%. In contrast, a urinary total metanephrine level > or = 9,000 nmol/day was both sensitive (100%) as well as specific (100%).


Nineteen years study of beta-thalassaemia in Slovakia.
Beta-thalassaemia is a congenital disorder caused by point mutations in a haemoglobin beta-globin chain. The heterozygous form produces microcytosis and normal iron levels, however, haemoglobin electrophoresis shows elevated amounts of haemoglobin A2 and eventually foetal haemoglobin F as well. Between 2005-2011, in three centres in Slovakia, carriers of beta-thalassaemic genes or other haemoglobinopathies were searched for. Diagnosis was performed by haematologists whereby the family history was evaluated, together with the overall clinical condition, blood count and blood smear, iron parameters, haemolysis and haemoglobin electrophoresis testing. A proportion of patients was examined by molecular genetic methods. A clinical suspicion of the heterozygous form of beta-thalassaemia was documented in 402 patients (21.9%) out of a total of 1,834 examinations. From these patients, 87 underwent molecular genetic testing and mutations of beta globin genes were identified in 70 of them, where the most frequent mutations were IVS 2.1 (28.5%), IVS 1.110 (25.6%) and IVS 1.1 (11.3%). Evidence of haemoglobin S (sickle cell anaemia) was also notable in one case (patient of African origin). Unusually high levels of haemoglobin F (6-21%) were found in 23 adult subjects. The study showed that there is a higher number of heterozygotes for beta-thalassaemia and rarely haemoglobinopathies. It is necessary to continue in search of pathological gene carriers in Slovakia.


Expression of baculovirus P35 prevents cell death in Drosophila.
The baculovirus P35 protein functions to prevent apoptotic death of infected cells. We have expressed P35 in the developing embryo and eye of the fly Drosophila melanogaster. P35 eliminates most, if not all, normally occurring cell death in these tissues, as well as X-irradiation-induced death. Excess pupal eye cells that are normally eliminated by apoptosis develop into pigment cells when their death is prevented by P35 expression. Our results suggest that one mechanism by which viruses prevent the death of the host cell is to block a cell death pathway that mediates normally occurring cell death. Identification of molecules that interact biochemically or genetically with P35 in Drosophila should provide important insights into how cell death is regulated.


Factors associated with planned and unplanned nuptial births.
The incidence of unplanned pregnancy in a cohort of 1038 mothers of nuptial children was examined. The major findings were: (1) about one third of the pregnancies were unplanned but there was little evidence that unplanned children were unwanted; (2) there was no evidence to suggest that unplanned birth was related to poor education, low socio-economic status or lack of knowledge of contraception; (3) 40 percent of unplanned births were the result of contraceptive failure; (4) a common denominator in 38 percent of unplanned births was failure or breakdown in the woman's usage of the contraceptive pill.


[Atypical presentation of an intestinal duplication in a three month old child].
Intestinal duplication is an uncommon congenital anomaly that often is diagnosed during childhood. Ultrasound diagnosis is based on the presence of a characteristic double-walled cystic mass. We report a case of duplication in a three Month old child presenting with small bowel obstruction. This case is unusual due to the presence of calcifications that are uncommon in intestinal duplication.


Outcome of surgical treatment for proximal long segment post intubation tracheal stenosis.
Post intubation long segment tracheal stenosis is a serious problem which usually requires multiple methods of treatment. The aim of this study was to evaluate the results of surgical treatment in long segment post intubation tracheal stenosis. Between 2004 to 2008, 20 patients with proximal long segment tracheal stenosis and resection of over 40% of tracheal length, were analyzed in terms of age, sex, clinical symptoms, etiology of stenosis, length of stenosis and resection, role of suprahyoeid release with bilateral hyoeid bone cutting maneuver, post operative complications and life quality 3 year after surgery. M/F was 2/5, with the average age of 23.5 ± 0.5 years. Average length of stenosis was 4.2 ± 0.4 cm and the average length of resected segment was 5.2 ± 0.4 cm. Early postoperative complications occurred in 4 patients (20%), 5 patients (25%) had late stenosis and 4 of them were treated with multiple dilation and one patient needed tracheostomy and prolonged T. tube. We didn't have any mortality. 80% of patients had excellent surgical results in follow up period. Surgery is the best method of treatment in long and multi segment tracheal stenosis.


High resolution MR imaging of peripheral joints using a quadrature coil at 0.35 T.
The utility of a specially dedicated quadrature detection (QD) mode limb coil for the MR evaluation of peripheral joints has been evaluated. High resolution images of the knee, elbow, wrist and ankle provided excellent anatomical delineation of the cortical and medullary bone, cartilage, ligaments and menisci over a homogeneous field of view. Pathological conditions including meniscal injury, fracture and osteonecrosis were accurately detected. The QD limb coil can be advantageously used for the MR evaluation of peripheral joints at an intermediate field strength.