Insulin-like growth factor I stimulates apical sodium/hydrogen exchange in human proximal tubule cells.
To determine whether insulin-like growth factor I (IGF-I) stimulated apical sodium/hydrogen exchange (NHE), confluent primary human proximal tubule cells (PTC) were incubated for 48 h in serum-free media in the presence or absence of 100 ng/ml IGF-I. Cells incubated in IGF-I demonstrated significant increases in thymidine incorporation (181.2 +/- 30.3% of control values; n = 12, P = 0.01) and in resting intracellular pH (pHi) (7.52 +/- 0.08 vs. 7.30 +/- 0.06; n = 20, P < 0.05), as determined by 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein quantitative microspectrofluorometry. Following intracellular acid loading, ethylisopropylamiloride (EIPA)-inhibitable H+ efflux and 22Na+ influx after 1 min were both significantly enhanced in IGF-I-treated cells compared with controls (8.78 +/- 1.69 vs. 3.03 +/- 0.72 mM/min and 3.47 +/- 0.49 vs. 1.55 +/- 0.35 nmol x mg protein(-1) x min(-1), respectively). 22Na+ uptake studies in PTC grown on permeable supports demonstrated preferential stimulation of apical vs. basolateral NHE. The 50% inhibitory concentrations (IC50) in IGF-I-treated and control cells for EIPA (0.5 and 1.1 microM, respectively) and for HOE-694 (4.0 and 10.0 microM, respectively) were also consistent with predominant activation of apical, rather than basolateral, NHE activity. Kinetic analysis revealed an increase in maximal transport velocity (Vmax, 15.50 +/- 1.50 vs. 7.26 +/- 3.07 mM/min; n = 10, P < 0.05), without a significant change in antiporter affinity for extracellular Na+. Incubation of PTC with 100 ng/ml IGF-I produced an acute, reversible, and EIPA-inhibitable pHi increase of 0.05 +/- 0.01 pH units (n = 5, P < 0.05). The results suggest that IGF-I may contribute to the metachronous stimulation of apical NHE and PTC growth observed in many physiological and pathological conditions involving the human kidney.


12-O-tetradecanoyl phorbol-13-acetate potentiates adenosine 3',5'-monophosphate-mediated chorionic gonadotropin secretion by cultured human choriocarcinoma cells.
The activation of protein kinase C and adenylate cyclase in the regulation of human CG (hCG) synthesis by cultured BeWo choriocarcinoma cells was studied. Both cholera toxin (CT), which activates adenylate cyclase, and 12-O-tetradecanoyl phorbol-13-acetate (TPA), a protein kinase C activator, stimulated the secretion of hCG in a dose-dependent manner. During a 72-h culture, stimulation with the maximal effective concentration of CT (1.0 ng/ml) exerted a more pronounced increase (16-fold) in hCG synthesis than TPA (10 ng/ml) (2.8-fold), whereas the inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate (100 ng/ml) was ineffective. When added together, TPA potentiated the effect of CT on hCG secretion (from 16- to 27-fold) and cAMP accumulation (from 36- to 54-fold) in the medium. TPA (1.0 ng/ml) also caused a 2.0-fold increase in basal cAMP production after 72 h. Time-course studies indicated that the effect of TPA on CT-induced cAMP and hCG productions became significant at 45 min and 6 h, respectively, from the beginning of stimulation. Proliferation of cells was not responsible for the responses, since the treatments only slightly increased the total protein content and did not alter the rate of incorporation of C3H3-methylated thymidine of the cells. Our results demonstrate that TPA potentiates CT-induced cAMP and hCG production in cultured human choriocarcinoma cells.


Chromium determinations in blood cells: clinical relevance demonstrated in patients with diabetes mellitus type 2.
As an essential nutrient involved in carbohydrate and lipid metabolism, chromium is of extraordinary importance for patients with diabetes. Plasma concentrations do not reflect the chromium supply; thus, we determined the element's content in blood cells in order to evaluate the body status. We investigated 86 blood donors (C) and 35 diabetics type 2 (Dm2). After the isolation of the blood cells by using a density centrifugation, the chromium concentrations were determined by electrothermal atomic absorption spectrometry. Compared to C, Dm2 had higher values in plasma, erythrocytes, and platelets (248%, 61%, and 91%, respectively) and lower contents in polymorphonuclear and mononuclear leukocytes (each -35%, age- and sex-matched groups with n=35, each p<0.01). The poorer the metabolic control assessed by HbA1c, the higher were the chromium concentrations in plasma (r=+0.46, n=33, p=0.007, increase 11.1% per %HbA1c) and the lower were the values in mononuclear leukocytes (r=-0.45, n=33, p=0.008, decrease 17.8% per %HbA1c). The changed amounts in plasma and in mononuclear cells in increasing hyperglycemia could be the result of an intracellular/extracellular redistribution of the element. High plasma levels might explain the renal chromium losses of diabetics, whereas the lymphocytes could reflect a decreasing chromium body state.


The effect of post stroke depression on functional outcome and quality of life.
In spite of being a common and important complication of stroke, post stroke depression is often overlooked, so its impact on stroke outcome remains under recognized. The aim of the study was to determine the effect of depression on functional outcome and quality of life in stroke patients. The study included 60 patients treated for their first clinical stroke, 30 of them diagnosed with depression and 30 patients without depression. Testing was done in all patients two and six weeks after stroke. Depression was diagnosed according to the Mini International Neuropsychiatry Interview, DSM-IV diagnostic criteria, and depression severity was quantified by the Hamilton Depression Rating Scale; functional impairment was determined by the Barthel Index; and post stroke quality of life was assessed by the Short Form 36 (SF-36) questionnaires. The patients with depression had significantly more severe functional disability both at baseline and after rehabilitation treatment, although the potential for functional recovery in depressed patients was less than in non-depressed ones. The quality of life in patients with post stroke depression was impaired more severely in all SF-36 domains compared with non-depressed stroke patients, with the domains of the role of emotional functioning and social relations being most severely affected.


[Oxidative stress in mechanism of psychosomatic disorders realization in duodenal ulcer in students].
To study the role of oxidative stress in mechanism of psychosomatic disorders involvement in pathogenesis of ulcerogenesis. Psychosomatic disorders (PSD) and oxidative stress (OS) were assessed in 120 students with duodenal ulcer (DU) who had no concomitant pathology. Examination for PSD included interviewing by questionnaires. OS was judged by the level of lipid peroxidation products (malonic dialdehyde and dienic conjugates) and antioxidant activity--by glutathion peroxidase and superoxidedismutase. Melatonin was measured by enzyme immunoassay. A close correlation was discovered between the severity and features of PSD, lowering of melatonin, severity of OS and clinical features of the disease. DU students develop PSD which become leading factors of ulcerogenesis. One of the mechanisms of their participation in ulcerogenesis may be related with lowering of melatonin which is a potent stress regulator and corrector of lipid peroxidation and antioxidant activity.


Inadequate levels of essential nutrients in developed nations as a risk factor for disease: a review.
Inadequate levels of essential nutrients is a most important factor in environmental health, leading to an almost monotonic increase in the incidence, morbidity, mortality, and associated costs of 'diseases of affluence' that has persisted for circa a century. Such an unprecedented human tragedy can be explained by the (1) flawed belief that essential nutrients can be replaced by xenobiotic molecules--a fundamental error, (2) failure to recognize that the levels of certain essential nutrients in diets available in the environment are not adequate to produce optimum health, longevity or resistance, and (3) failure to recognize that the refined diet has a lower essential nutrient content. Such beliefs contribute to early death in affluent nations.


i3b3: Infobuttons for i2b2 as a Mechanism for Investigating the Information Needs of Clinical Researchers.
The information needs of clinicians, as they interact with the EHR, are well-studied. Clinical researchers also interact with the EHR and, while they might be expected to have some similar needs, the unique needs that arise due to nature of their work remain largely unstudied. For clinicians, infobuttons (context-aware hyperlinks) provide a mechanism of studying these information needs. Here we describe the integration of infobuttons into i2b2, a popular data warehouse commonly used by clinical researchers, using a plugin. A preliminary survey of i2b2 developers suggests a general interest in infobuttons for i2b2 and indicates good likelihood for their deployment, where they may be used as a tool for further studying these needs in greater detail.


Adrenal incidentaloma: an overview of clinical and epidemiological data from the National Italian Study Group.
The incidental discovery of an adrenal mass raises the problem of distinguishing the frequent benign masses from the infrequent malignant ones that require surgery. At present, univocal guidelines to approach this problem are not available. The aim of the present study was to perform a multicentric retrospective analysis of adrenal masses incidentally discovered (adrenal incidentalomas). Hospital records of adrenal incidentalomas diagnosed over a 15-year period in 29 surgical and medical centers in Italy were scrutinized. Collected cases were 1,013, and 887 were analyzed. The majority of patients were in the 5th and 6th decade and females were predominantly affected. The frequency of adrenocortical cancer was 12% among operated patients (316 cases). The tumor diameter was highly correlated with the risk of malignancy, as well as the CT characteristics such as density, shape and margins. The frequency of pheochromocytoma was 10% among operated patients. The occurrence of incidentally discovered adrenocortical carcinomas and pheochromocytomas is not rare. Evaluation of the mass size and CT characteristics are simple and effective methods to differentiate malignant lesions. Biochemical screening for pheochromocytoma is mandatory before surgery.


Primary angioplasty for heart attack: mismatch between expectations and reality?
This paper is a report of a study to explore patients' experiences of primary angioplasty and assess their illness perceptions during early recovery. Primary angioplasty is recognized as the gold standard treatment for patients with ST elevation myocardial infarction, yet little is known about patients' experiences of this treatment. Recent policy change has emphasized the need for clinical practice to be more patient-centred. One way to achieve this is to understand patients' experiences of treatment better. A mixed methods exploratory study was carried out in 2006-2007 with a purposive sample of 29 patients. Data were collected 3-12 days after hospital discharge using (a) semi-structured interviews to explore participants' experiences and (b) The Illness Perception Questionnaire to evaluate illness perceptions. Interview data were analysed using the Framework approach. Questionnaire data were used to inform the qualitative findings. Participants were very positive about their treatment but experienced considerable emotional shock, which was exacerbated by the speed with which events occurred. Patients' experiences were characterized by a mismatch between their expectations and reality. Questionnaire data supported the notion that they experienced difficulty in 'making sense' of their condition in a coherent way. They tended to see their condition as 'acute' rather than 'chronic' and their treatment as curative. Patient education should include focused discussions addressing the 'mismatches' that may occur between their expectations and reality. In this way, a more coherent understanding can be promoted, with greater awareness of heart disease as a long-term condition requiring ongoing self-management.


Popular Criteria for the Welfare Deservingness of Disability Pensioners: The Influence of Structural and Cultural Factors.
Research has shown that several criteria underlie people's opinions about the welfare deservingness of benefit recipients. However, it remains unknown which factors are associated with the emphasis that people place on such criteria. Using a 2006 Dutch national survey on the welfare deservingness of disability pension recipients, we study the influence of structural and cultural factors on people's emphasis on three deservingness criteria: control, need, and reciprocity. OLS regression analyses show that people's emphasis on specific deservingness criteria is strengthened by structural factors that indicate the possibility of resource competition such as the following: age, lower levels of education, unemployment, and lower income. However, actual personal experience with receiving welfare benefits weakens criteria emphasis. Cultural factors such as the espousal of views from the political right and the possession of a strong work ethic are associated with a heightened emphasis on deservingness criteria.


Quantitative analysis of low molecular weight polar compounds by continuous flow liquid secondary ion tandem mass spectrometry.
Quantitative analyses of low molecular weight (100-200) polar compounds [1-methyl-4-phenylpyridine (MPP+), 2-amino-3-(methylamino)propanoic acid (synonyms, beta-(methyl-amino)-L-alanine or BMAA), and tryptophan] were conducted on a triple-stage quadrupole mass spectrometer configured for continuous flow liquid secondary ion mass spectrometry ionization (CF L-SIMS). It is shown that quantification by CF L-SIMS at subnanogram sensitivity can be precise (correlation coefficients greater than 0.99), accurate, specific, and routine for compounds not measurable by static L-SIMS. Successful analyses, however, are strongly dependent upon the stability of the film formed by the mobile phase on the probe tip. In our system, film stability is affected by mobile phase composition and flow rate, ion source and probe tip temperature, probe-tip and capillary alignment, film thickness, and sample composition.


Perspectives on mealtime management in residential aged care: insights from a cross-disciplinary investigation.
Meeting the medical, nutritional, and psychosocial mealtime needs of aged care residents requires a holistic, multidisciplinary approach. To date the perspectives of this multidisciplinary team have not been adequately explored. The aim of this study was to explore the perspectives of a range of service providers involved in mealtime management in residential aged care. In-depth semistructured interviews were conducted with 61 participants from five service disciplines. Four themes emerged: ( 1 ) mealtimes are highly valued; ( 2 ) service providers face common barriers to mealtime management; ( 3 ) communication among service providers is challenging; and ( 4 ) education in mealtime management is limited. Data indicated service providers acknowledge the importance of mealtimes but recognize numerous shortfalls in current care. The need for interdisciplinary training and increased communication and collaboration among providers was emphasized, including the need for clarification of provider roles. Limited consideration of mealtimes in policy and funding documents was identified as a primary barrier in further prioritizing mealtime management and advancing mealtime care.


Motives to study and socialization tactics among university students.
The authors focused on the period following students' admission to university and examined the effects of students' motives to study and socialization tactics on their academic achievement and academic satisfaction. The authors hypothesized that socialization tactics would mediate the relation of motives to study to academic achievement and satisfaction. The findings confirmed the hypotheses and highlighted the importance of students' socialization tactics in the university setting. In addition, the research provided a typology to distinguish different types of socialization tactics.


Multicenter comparison of dilevalol to placebo in patients with mild hypertension.
The antihypertensive effects of oral dilevalol, a beta-blocking agent with vasodialating properties were compared with placebo in 128 mildly hypertensive patients (supine diastolic blood pressure 95 to 105 mm Hg) in a multicenter, double-blind, parallel group study. Following a 4-week placebo phase, 63 patients were randomly assigned to receive dilevalol and 65 to receive placebo. A titration phase followed during which the dose of dilevalol was increased every other week from 100 mg to 800 mg to achieve a supine diastolic blood pressure (SDBP) less than 90 mm Hg and decreased by 10 mm Hg or more from baseline. A matching number of placebo capsules for each dose level of dilevalol was dispensed for blinding purposes. Patients who had at least a 5 mm Hg reduction in SDBP entered a 1-month maintenance phase. Blood pressure and heart rate were measured weekly 20 to 24 hours after a dose. This study demonstrated that the minimally effective dose of dilevalol was 100 mg, which was shown to result in a significantly (P less than or equal to 0.05) greater reduction in systolic BP. A once-daily dose of 200 mg was superior to placebo in both systolic and diastolic BP effects (P less than 0.001 and less than 0.001, respectively), and this superiority was seen again at both the end of titration and the end of the study. The BP reduction was accompanied by a small (5 bpm) decrease in heart rate. The side effect profile of dilevalol was not different from placebo. Dilevalol appears to have no adverse effect on plasma lipids.(ABSTRACT TRUNCATED AT 250 WORDS)


Doctor Foster 'went' to Gloucester: the origin and aims of The Royal College of Psychiatrists.
In 1841 Dr Samuel Hitch organised a meeting at Gloucester Lunatic Asylum during which a decision was taken to establish the Association of Medical Officers of Asylums and Hospitals for the Insane with a view to "improvement in the management of such institutions and the treatment of the insane, and the acquirement of a more extensive and more correct knowledge of insanity". From the six medical officers present at this historic meeting the membership of The Royal College of Psychiatrists has grown to more than 11,000, of whom over 1,500 practise overseas. Dr Mike Shooter (President) believes that the College's most important, and painful, transformation has been from a largely educational to a political organisation.


High rates of energy expenditure and water flux in free-ranging Point Reyes mountain beavers Aplodontia rufa phaea.
We measured water flux and energy expenditure in free-ranging Point Reyes mountain beavers Aplodontia rufa phaea by using the doubly labeled water method. Previous laboratory investigations have suggested weak urinary concentrating ability, high rates of water flux, and low basal metabolic rates in this species. However, free-ranging measurements from hygric mammals are rare, and it is not known how these features interact in the environment. Rates of water flux (210+/-32 mL d(-1)) and field metabolic rates (1,488+/-486 kJ d(-1)) were 159% and 265%, respectively, of values predicted by allometric equations for similar-sized herbivores. Mountain beavers can likely meet their water needs through metabolic water production and preformed water in food and thus remain in water balance without access to free water. Arginine-vasopressin levels were strongly correlated with rates of water flux and plasma urea : creatinine ratios, suggesting an important role for this hormone in regulating urinary water loss in mountain beavers. High field metabolic rates may result from cool burrow temperatures that are well below lower critical temperatures measured in previous laboratory studies and suggest that thermoregulation costs may strongly influence field energetics and water flux in semifossorial mammals.


SY-Net: A Rice Seed Instance Segmentation Method Based on a Six-Layer Feature Fusion Network and a Parallel Prediction Head Structure.
During the rice quality testing process, the precise segmentation and extraction of grain pixels is a key technique for accurately determining the quality of each seed. Due to the similar physical characteristics, small particles and dense distributions of rice seeds, properly analysing rice is a difficult problem in the field of target segmentation. In this paper, a network called SY-net, which consists of a feature extractor module, a feature pyramid fusion module, a prediction head module and a prototype mask generation module, is proposed for rice seed instance segmentation. In the feature extraction module, a transformer backbone is used to improve the ability of the network to learn rice seed features; in the pyramid fusion module and the prediction head module, a six-layer feature fusion network and a parallel prediction head structure are employed to enhance the utilization of feature information; and in the prototype mask generation module, a large feature map is used to generate high-quality masks. Training and testing were performed on two public datasets and one private rice seed dataset. The results showed that SY-net achieved a mean average precision (mAP) of 90.71% for the private rice seed dataset and an average precision (AP) of 16.5% with small targets in COCO2017. The network improved the efficiency of rice seed segmentation and showed excellent application prospects in performing rice seed quality testing.


Parasitoids as drivers of symbiont diversity in an insect host.
Immune systems have repeatedly diversified in response to parasite diversity. Many animals have outsourced part of their immune defence to defensive symbionts, which should be affected by similar evolutionary pressures as the host's own immune system. Protective symbionts provide efficient and specific protection and respond to changing selection pressure by parasites. Here we use the aphid Aphis fabae, its protective symbiont Hamiltonella defensa, and its parasitoid Lysiphlebus fabarum to test whether parasite diversity can maintain diversity in protective symbionts. We exposed aphid populations with the same initial symbiont composition to parasitoid populations that differed in their diversity. As expected, single parasitoid genotypes mostly favoured a single symbiont that was most protective against that particular parasitoid, while multiple symbionts persisted in aphids exposed to more diverse parasitoid populations, which in turn affected aphid population density and rates of parasitism. Parasite diversity may be crucial to maintaining symbiont diversity in nature.


Construction and hemocompatibility study of highly bioactive heparin-functionalized surface.
A simple method is developed to construct anticoagulant surfaces via passive adsorption of heparin onto the protonated plasma-polymerized allylamine (PPAam) films from phosphate-buffered saline (PBS). These protonated PPAam surfaces are found to have high affinity to heparin. Importantly, the heparin-functionalized PPAam (Hep-PPAam) surfaces show good retention of heparin after long-term immersion in PBS. The Hep-PPAam surface prolongs the activated partial thromboplastin time for about 20 s as compared to 316L stainless steel even though the adsorption amount of heparin is only about 300 ng/cm(2). This indicates that the heparin bound to the protonated PPAam surfaces in this way maintains a high bioactivity. Blood platelet adhesion and activation on this surface is remarkably reduced and adsorption and activation of fibrinogen is inhibited. Thus, Hep-PPAam surface modification leads to a significant improve of the hemocompatibility.


Invagination of a shunt valve: an unusual complication--case report.
The authors present an unusual case of ventriculoperitoneal shunt failure due to invagination of a valve in the proximal portion of the silicone casing of the shunt system. The shunt had been in place for 5 years and the 57-year-old male patient had incurred no head injury during that period. The valve failure was discovered during evaluation of his gradual deterioration, which culminated in his functional incapacitation. Nine such cases have been reported in the literature. This complication is specifically associated with the Holter and Hakim valves and seems to a primary mechanical failure attributable to the structure of these two valves.


A new phenylpropanoid glycoside from Jasminum subtriplinerve Blume.
From the ethyl acetate extract of the aerial parts of Jasminum subtriplinerve Blume (Oleaceae), 6'-O-menthiafoloylverbascoside (1), rutin (2), isoverbascoside (4), isooleoverbascoside (6), apiosylverbascoside (7), astragalin (9), isoquercitrin (10), and verbascoside (11) were isolated. Their structures were elucidated by extensive MS and NMR spectroscopy. Amongst 6'-O-menthiafoloylverbascoside (1) is a new phenylpropanoid glycoside.


Feasibility of a Responsibility-Based Leadership Training Program for Novice Physical Activity Instructors.
Most coaches and instructors would like to teach more than just sport skills to their athletes and children. However, to promote athletes' or children's holistic development and teach them to take responsibility and lead, requires the coaches and instructors to first master the skills themselves. Therefore, feasible, high quality leadership training programs where coaches and physical activity instructors are taught to teach and share leadership are needed. The aim of the current study was to evaluate the feasibility of a leadership training program to optimize it and to determine whether to proceed with its evaluation. In the leadership training program, eight Finnish novice physical activity instructors, aged 18 to 22, were taught to promote positive youth development, personal and social responsibility, and shared leadership in a physical activity context. The participants had minimal to no leadership training or experience. The training program consisted of seven meetings totaling 20 h. Helllison's teaching personal and social responsibility (TPSR) model was the theoretical and practical framework of the training program. Feasibility of the leadership training program was evaluated across four domains of an evidence-based framework: demand, practicality, acceptability, and implementation fidelity. Data of the current complex intervention were collected with application videos, questionnaires, researcher's log, lesson plans, video recordings, and a semi-structured focus group interview. The quantitative data were analyzed using descriptive statistics and the qualitative data using deductive and inductive content analysis. There was a demand for the leadership training program. The training program was perceived as practical and highly acceptable by the novice instructors and the trainers, and implemented with fidelity, indicating high overall feasibility. No implementation issues were found. Consequently, the current leadership training program has a high probability of efficacy and can be accepted for further evaluation.


Structure/activity and molecular modeling studies of the lophotoxin family of irreversible nicotinic receptor antagonists.
Lophotoxin is a small cyclic diterpene that irreversibly inhibits agonist binding to nicotinic acetylcholine receptors by reacting covalently with Tyr190 in the alpha-subunits of the receptor. Structure/activity and molecular modeling studies were undertaken to investigate the structural and conformational features responsible for this unique biological activity. A total of 18 naturally occurring and 7 chemically modified analogues were evaluated for their ability to inhibit the binding of [125I]-alpha-bungarotoxin to nicotinic acetylcholine receptors on membranes prepared from Torpedo electric organ. When the toxins were incubated with the receptor for short durations they did not slow the initial rate of binding of [125I]-alpha-bungarotoxin, suggesting that they have relatively low reversible affinity. However, their ability to inhibit the equilibrium binding of [125I]-alpha-bungarotoxin increased progressively with longer incubation times, consistent with an irreversible mechanism of action. Comparison of active and inactive analogues allowed identification of a conserved pharmacophore that appeared to be required for irreversible inhibition of the receptor. This pharmacophore contains lactone oxygens and an electron-deficient epoxide that may mimic the acetate oxygens and quaternary ammonium group of acetylcholine, respectively. Computer modeling of the toxins using molecular mechanics and dynamics revealed that the toxins have restricted conformational mobility, thus allowing identification of a minimum-energy conformation. The results allow speculation concerning the site of covalent reaction between Tyr190 and the toxins, the normal function of Tyr190 in binding acetylcholine, and the bound conformation of acetylcholine.


[Gynecological urologic disease: a summary of clinical experience during the last 4 years at Wakayama Red Cross Hospital].
From April 1979 to March 1983, sixty seven patients with gynecological urologic disease were experienced at our department. Forty one of them were inpatients, i.e., 15.3% of the total number of female in patients admitted during the same period. Thirty three urologic operations were performed on them which corresponded to 16.1% of the total operations on female patients. Ten of these patients had ureteral obstruction following gynecological operation, 8 had ureteral fistula, 7 had vesicovaginal fistula, 11 had tumor invasion to urinary tract, 14 had radiation cystitis, 16 had neurogenic bladder dysfunction, and 1 had other complication. The treatment of these patients and the results are summarized and discussed.


Management of the malignant polyp.
Colonoscopy and endoscopic polypectomy are being utilized more frequently these days with the increased emphasis on the prevention, early detection, and treatment of colon cancer. Consequently, the problem of managing the malignant polyp is likely to be more frequently encountered. Many attempts have been made to clarify the management principles involved. Although the studies conducted have been imperfect in their design, the variety of information obtained from these studies is making the picture clearer. A more conservative approach is evolving. Many malignant polyps may be managed by endoscopic polypectomy alone. The criteria for which patients are to be managed in this fashion seem to be relatively simple ones, though technical problems with polypectomy performance and histologic evaluation are still frequently encountered. More carefully designed long-term studies are needed to create firm guidelines for the management of malignant polyps. Should screening and surveillance result in the discovery of earlier and more readily treatable forms of invasive colon cancer, endoscopic polypectomy will most certainly be a cornerstone of their treatment.


Rheological investigation of specific interactions in Na Alginate and Na MMT suspension.
Here we report on a study of a rheological behavior of sodium alginate and montmorillonite suspension. We find that viscoelastic behavior of this suspension is dramatically affected with increasing volume fraction of montmorillonite platelets. Addition of montmorillonite generally leads to gel formation, which is attributed to interactions of montmorillonite and alginate via H-bonding and attraction between the positive edges of the platelets and the anionic backbone of the biopolymer. A critical concentration for the measured system was observed at 20wt.% montmorillonite, where a crossover to a gel-like structure was detected. The observed gel has a rubber plateau, which develops further with higher montmorillonite concentration. In this physical gel the relaxation maximum was detected, which is associated with the breaking and reformation of the bonds between the platelets and the biopolymer. For this transient behavior, we find that a Maxwell type viscoelasticity quite well describes the relaxation time and the observed G'-G" crossover. We believe that this gel-like behavior plays an important role in formation of highly ordered nanostructures that develop during the drying of these bio-nanocomposite suspensions.


Two promising measures of health education program outcomes and asthmatic children.
Two measures of health education program outcomes were administered to a group of 50 asthmatic children: the Child's Health Locus of Control Scale and the Piers-Harris Children's Self Concept Scale. Interest centered on the reliabilities and discriminant validity of these instruments. Results showed high alpha reliabilities for both scales and a low, positive intercorrelation. Mean health locus of control and self-concept scores for this group were comparable to those of healthy children. These findings may be useful in designing and evaluating health education programs for children with asthma.


Does progesterone have protective effects on ovarian ischemia-reperfusion injury?
The aim of the present study was to evaluate the effects of progesterone (PG) against ovarian ischemia-reperfusion (I/R) injury through the evaluation of biochemical and histopathologic parameters. Twenty-one female Wistar albino rats were divided into three groups. Group 1: Sham; group 2: I/R; group 3: I/R+PG (8 mg/kg). PG was administered intraperitoneally to the rats in group 3, 30 minutes before a detorsion operation. Ovarian I/R injury was evaluated in serum and tissue by using biochemical parameters including malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index, neutrophil gelatinase-associated lipocalin (NGAL) and immunofluorescence staining by using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Serum and tissue TOS levels were significantly lower in group 3 than in group 2. Tissue TAS levels were higher in group 3 than in group 2 (p<0.001). NGAL and MDA levels were similar between the groups. Histologic score, including vascular congestion, hemorrhage, polymorphonuclear neutrophils, and interstitial edema, was higher in group 2. Pre-treatment with PG decreased the score, but this difference was not statistically significant. The number of apoptotic cells was higher in group 2 than in groups 1 and 3. The TUNEL-positive cell number decreased with PG in group 3. Preoperative PG treatment might exert protective effects on ovarian I/R injury through its anti-apoptotic and antioxidative properties.


Intra-cameral level of ganciclovir gel, 0.15% following topical application for cytomegalovirus anterior segment infection: A pilot study.
To investigate the intra-cameral level of ganciclovir following topical application of ganciclovir gel, 0.15% for cytomegalovirus (CMV) anterior segment infection. Non-randomized, prospective, interventional clinical study. Patients with active CMV anterior segment infection seen at Singapore National Eye Centre, confirmed by positive CMV real time PCR (RT-PCR) of the aqueous humor, that had not been treated with any form of ganciclovir in the preceding 1 month were recruited. They were treated with ganciclovir gel, 0.15% 1cc 5 times a day. Following 6 weeks of treatment, CMV load in the aqueous humor was measured using CMV RT-PCR and the ganciclovir drug levels in tears and aqueous humor were measured using high-performance liquid chromatography-mass spectrometry. The clinical features of the disease activity and the central corneal thickness (CCT) were recorded at the baseline and post-treatment. There were 29 eyes of 29 patients, of which 23 eyes had CMV anterior uveitis and 6 eyes had CMV endotheliitis. At the end of week 6, 26 eyes had undetectable CMV titre in the aqueous humor and no anterior chamber (AC) activity. Two patients had an increased CMV titre and increased AC inflammation. Both of these patients were non-compliant with the treatment. One patient had a reduced CMV titre in the aqueous humor with minimal AC inflammation. The mean ganciclovir concentration in the aqueous humor and the tears were 17.4 ± 30.6 ng/ml and 20,420.9 ± 33,120.8 ng/ml respectively. Mean CCT was 552.2 ± 42.3 microns. There was a weak correlation between the ganciclovir concentration in the aqueous humor and CCT (Spearmen's r = + 0.42, p = 0.025). There was no significant correlation between the ganiclovir concentration in the tears and CCT (Spearmen's r = + 0.39, p = 0.11). Ganciclovir levels in the aqueous humor was below the 50% inhibitory dose (ID50) for CMV replication, following topical application of the ganciclovir gel, 0.15%. SingHealth Centralized Institutional Review Board, Singapore; R733/17/2010, ClinicalTrials.gov; NCT01647529.


Combined anteversion technique in total hip arthroplasty for Crowe IV developmental dysplasia of the hip.
A high rate of postoperative dislocation in total hip arthroplasty (THA) for Crowe IV developmental dysplasia of the hip (DDH) has been reported, 1 of the main reasons being higher true acetabular anteversion. If the cup is fixed with normal anteversion, the anterior rim will be excessively exposed, which reduces the contact areas of the cup and bone, affects prosthesis stability, and leads to iliopsoas tendinitis and persistent hip pain after THA. The aim of this study was to demonstrate that when cup anteversion is larger, adjusting femoral anteversion to bring the combined anteversion (CA) into the "safe zone" might prevent dislocation. After having fixed the cup in the acetabulum according to the patients' native acetabular anteversion, we shortened and rotated the proximal femur to reduce femoral anteversion, adjusting the CA into the "safe zone". The Harris Hip Score (HHS) was used to evaluate hip joint function. Computerised tomography scanning was used to measure the anteversion angles. All patients were followed up without any dislocation. Preoperative and 12 months after surgery, the mean HHS were 43.3 ± 2.6 (38-47) and 88.1 ± 3.3 (78-92) respectively. Pre- and post-operation, the mean CA angles were 88.6° ± 9.4° (80.3°-119.4°) and 49.2° ± 2.6° (43.4°-54.4°) respectively. The bone healing time of femoral osteotomy ranged from 4 to 14 months, with a mean time of 7.5 months. This CA technique in THA for Crowe IV DDH can effectively prevent postoperative dislocation and provide good hip function.


Histogenesis of the human adrenal medulla. An evaluation of the ontogeny of chromaffin and nonchromaffin lineages.
The authors previously evaluated the expression of a panel of chromaffin-related genes during histogenesis of the human adrenal medulla. In these studies, chromaffin and nonchromaffin adrenal neuroblasts were identified. To better characterize these nonchromaffin neuroblasts, the authors evaluated two additional markers: HNK-1, an antibody recognizing the migratory neural crest cell; and S-100, a protein expressed by sustentacular cells of the adrenal medulla. HNK-1 immunoreactivity was found in both chromaffin and nonchromaffin cell types at different times during development, marking the nonchromaffin lineage during the second trimester of gestation as well as the chromaffin lineage in the neonatal period. In addition, S-100 expression was noted in some nonchromaffin neuroblasts, and sustentacular cells were first identified at approximately 28 weeks of gestational age. These data suggest a model of human adrenal medullary histogenesis that incorporates the chromaffin, ganglionic, and sustentacular lineages known to constitute the adult adrenal medulla.


Clinical-instrumental and morphological evaluation of the effect of autologous dermal fibroblasts administration.
Basic molecular mechanisms, associated with the main cell population of the dermis - fibroblasts - are the basis of skin aging. The number of functionally active fibroblasts in the skin and their biosynthetic activity decreases with age, thus enhancement of their cell density with synthetically active cells is accepted as a one of the most effective methods. The objective of the present study was to evaluate the safety and effectiveness of intradermal administration of autologous dermal fibroblasts in a year after treatment of 17 patients, aged 45-65 years. Results obtained with modern instrumental skin diagnostic methods (vacuum cutometry, optical profilometry, VISIA photometric analysis, etc.) demonstrate the safety and clinical effectiveness of dermal autofibroblast therapy: after transplantation, cultured autofibroblasts keep their biosynthetic activity and produce extracellular matrix for at least 12 months. As a result, remodelling of the dermis microstructures is observed, accompanied by a progressive increase of collagen content and thickness of the dermis (up to 62.5 ±6.7% in 12 months). This is clinically expressed by increase of skin elasticity (24.0 ±4.3% in periorbital area) and thickness of the skin, and by decrease in the number and depth of wrinkles (46 ±7% by the end of observation period). Copyright © 2014 John Wiley & Sons, Ltd.


The GALAXIES inelastic hard X-ray scattering end-station at Synchrotron SOLEIL.
GALAXIES is an in-vacuum undulator hard X-ray micro-focused beamline dedicated to the study of the electronic structure of materials with high energy resolution using both photoelectron spectroscopy and inelastic X-ray scattering and under both non-resonant (NR-IXS) and resonant (RIXS) conditions. Due to the penetrating power of hard X-rays and the `photon-in/photon-out' technique, the sample environment is not a limitation. Materials under extreme conditions, for example in diamond anvil cells or catalysis chambers, thus constitute a major research direction. Here, the design and performance of the inelastic X-ray scattering end-station that operates in the energy range from ∼4 keV up to 12 keV is reported, and its capabilities are highlighted using a selection of data taken from recently performed experiments. The ability to scan `on the fly' the incident and scattered/emitted X-ray energies, and the sample position enables fast data collection and high experimental throughput. A diamond X-ray transmission phase retarder, which can be used to generate circularly polarized light, will also be discussed in the light of the recent RIXS-MCD approach.


Epidemiology of liver cancer: an overview.
The incidence of liver cancer varies widely throughout the world, with high rates in sub - Saharan Africa, eastern and southeastern Asia, and Melanesia and a low incidence in Northern and Western Europe and the Americas. Primary cancers of the liver in adults are of two main histological types: hepatocellular carcinoma, which is derived from hepatocytes, and cholangiocarcinoma, which is derived from the epithelial lining of the intrahepatic bile ducts. Hepatocellular cancer is a frequently occurring tumor in individuals in many developing countries, where several important risk factors have been demonstrated, including chronic infection with hepatitis B and C viruses and other environmental factors, such as exposure to aflatoxin, consumption of alcohol, and cigarette smoking. By contrast, cholangiocarcinoma is less common, accounting for only 7.7% of malignant tumors of the liver in the United States. However, in parts of Southeast Asia, cholangiocarcinoma occurs more frequently; it is responsible for more than 60% of liver tumors in northeastern Thailand. The geographic distribution worldwide coincides with endemic areas of the liver flukes, Opisthorchis viverrini and Clonorchis sinensis. The interaction between genes and the environment and the interplay of environmental factors, which include diet and other lifestyle parameters, illustrate the complexity underlying susceptibility.


A survey on teaching ultrasound-guided chronic pain procedures in pain medicine fellowship programs.
Over the last decade ultrasound guidance (USG) has been utilized very successfully in acute pain procedures to confirm nerves' anatomic location and obtain live images. Not only the utilization, but the teaching, of USG has become an essential part of anesthesiology residency training. Prior to the introduction of USG, chronic pain procedures were always done either under fluoroscopy or blindly. USG offers advantages over fluoroscopy for completion of chronic pain procedures. USG decreases radiation exposure and the expenses associated with operating a fluoroscopy machine and allows live visualization of soft tissues and blood flow, a feature that fluoroscopy does not directly offer. Even today, the utilization and teaching of the technique for chronic pain procedures has not been as widely accepted as in acute pain management. To understand the current practices and the factors affecting the teaching of ultrasound guided chronic pain procedures in chronic pain fellowship programs throughout the United States. Survey conducted by internet and mail. The survey was distributed to program directors of ACGME-accredited pain medicine fellowships. When the survey was distributed there were 92 accredited pain medicine fellowships. REDCap survey software was used for designing the questionnaire and sending email invitations. Also, paper questionnaires were sent to those who did not respond electronically. Additional copies of the survey were mailed or faxed upon request. We received 43 responses (a response rate of 46.7%). Statistical analyses included frequencies, crosstabs, and nonparametric Spearman rank-order correlations. The majority of stellate ganglion blocks, occipital nerve blocks, and peripheral nerve blocks are currently being done under ultrasound guidance. Although interest among trainees is very high, only 48.8% of the fellowship programs require fellows to learn the technique before graduation and 32.6% of the program directors agree that teaching of USG should be an ACGME requirement for pain medicine fellowship training. Faculty training is considered to be the most important factor for teaching the technique by 62.8% of directors. In the opinion of the majority of program directors, the greatest factor that stands against teaching the technique is the fact that it is time consuming. Nearly half (44.2%) of program directors believe that the technique will never replace fluoroscopy; but one quarter (25.6%) think that the new 3D ultrasound technology, when available, will replace fluoroscopy. A moderate response rate (46.7%) may limit the generalizability of the findings. However, our survey respondents seem to represent the study population quite well, although there was a bias towards the university-based programs. Training programs located at community-based hospitals and U.S. government installations were not as well represented. The teaching of ultrasound guided chronic pain procedures varies significantly between individual programs. Though many program directors do require that fellows demonstrate competency in the technique before graduation, as of today there is no ACGME guideline regarding this. The advancement in ultrasound technology and the increase in number of trained faculty may significantly impact the use of USG in training fellows to perform chronic pain procedures.


Full-field measurement of nonuniform stresses of thin films at high temperature.
Coherent gradient sensing (CGS), a shear interferometry method, is developed to measure the full-field curvatures of a film/substrate system at high temperature. We obtain the relationship between an interferogram phase and specimen topography, accounting for temperature effect. The self-interference of CGS combined with designed setup can reduce the air effect. The full-field phases can be extracted by fast Fourier transform. Both nonuniform thin-film stresses and interfacial stresses are obtained by the extended Stoney's formula. The evolution of thermo-stresses verifies the feasibility of the proposed interferometry method and implies the "nonlocal" effect featured by the experimental results.


Five-Year Safety and Efficacy of Femtosecond Laser-Assisted Descemet Membrane Endothelial Keratoplasty.
The purpose of this study was to evaluate 5-year safety and efficacy outcomes of femtosecond-enabled Descemet membrane endothelial keratoplasty (F-DMEK) in patients with Fuchs' endothelial dystrophy (FED). This was a retrospective study, including patients with FED and cataract who underwent either F-DMEK (16 eyes of 15 patients) or manual DMEK (M-DMEK) (42 eyes of 37 patients) combined with cataract extraction. Outcome measures included visual acuity, graft detachment, graft survival, and endothelial cell loss. The average follow-up in F-DMEK and M-DMEK was 57.1 ± 12.4 months and 58.5 ± 17.3 months, respectively ( P = 0.757). The rates of primary failure (0% vs. 9.5%, P = 0.567), secondary failure (0% for both), and graft rejection (0% vs. 7.1%, P = 0.533) did not differ significantly between the groups. Improvement in best spectacle-corrected visual acuity was similar in F-DMEK and M-DMEK (0.32 ± 0.27 logarithm of the minimum angle of resolution and 0.35 ± 0.44 logarithm of the minimum angle of resolution, respectively, P = 0.165) and persisted at 2, 3, 4, and 5 years and at the last follow-up. The rates of graft detachment and rebubbling were significantly lower with 6.25% in F-DMEK and 33.3% in M-DMEK ( P = 0.035). Cell-loss rates were lower in F-DMEK compared with M-DMEK throughout the follow-up, significantly so up to 2 years with a difference of 8.6% at 1 year ( P = 0.023), 11.8% at 2 years ( P = 0.021), 7.6% at 3 years ( P = 0.088), 5.8% at 4 years ( P = 0.256), 13.6% at 5 years ( P = 0.169), and 7.1% at the final follow-up ( P = 0.341). F-DMEK had an excellent safety and efficacy profile which was maintained over 5 years of follow-up. Lower endothelial cell-loss rates in F-DMEK compared with M-DMEK may help extend the duration of graft survival.


Repression of the prolactin promoter: a functional consequence of the heterodimerization between Pit-1 and Pit-1 beta.
The POU-homeodomain transcription factor Pit-1 is required for the differentiation of the anterior pituitary cells and the expression of their hormone products. Pit-1beta, an alternate splicing isoform, has diametrically different outcomes when it is expressed in different cell types. Pit-1beta acts as a transcriptional repressor of prolactin (PRL) and growth hormone genes in pituitary cells, and as a transcriptional activator in non-pituitary cells. In order to explore these differences, we: (1) identified the transcriptional cofactors necessary for reconstitution of repression in non-pituitary cells; (2) tested the effect of the beta-domain on heterodimerization with Pit-1 and physical interaction with the co-activator CREB binding protein (CBP); and (3) determined the beta-domain sidechain chemistry requirements for repression. Co-expression of both Pit-1 isoforms reconstituted the repression of the PRL promoter in non-pituitary cells. The beta-domain allowed heterodimerization with Pit-1 but blocked physical interaction with CBP, and specific chemical properties of the beta-domain beyond hydrophobicity were dispensable. These data strongly suggest that Pit-1beta represses hormone gene expression by heterodimerizing with Pit-1 and interfering with the assembly of the Pit-1-CBP complex required for PRL promoter activity in pituitary cells.


Intrinsic viscuit probability distribution functions for transport coefficients of liquids and solids.
A reformulation of the Green-Kubo expressions for the transport coefficients of liquids in terms of a probability distribution function (PDF) of short trajectory contributions, which were named "viscuits," has been explored in a number of recent publications. The viscuit PDF, P, is asymmetric on the two sides of the distribution. It is shown here using equilibrium 3D and 2D molecular dynamics simulations that the viscuit PDF of a range of simple molecular single component and mixture liquid and solid systems can be expressed in terms of the same intrinsic PDF (P0), which is derived from P with the viscuit normalized by the standard deviation separately on each side of the distribution. P0 is symmetric between the two sides and can be represented for not very small viscuit values by the same gamma distribution formulated in terms of a single disposable parameter. P0 tends to an exponential in the large viscuit wings. Scattergrams of the viscuits and their associated single trajectory correlation functions are shown to distinguish effectively between liquids, solids, and glassy systems. The so-called viscuit square root method for obtaining the transport coefficients is shown to be a useful probe of small and statistically zero self-diffusion coefficients of molecules in the liquid and solid states, respectively. The results of this work suggest that the transport coefficients have a common underlying physical origin, reflecting at a coarse-grained level the traversal statistics of the system through its high-dimensioned potential energy landscape.


Methionine metabolism in mammals. Adaptation to methionine excess.
We conducted a systematic evaluation of the effects of increasing levels of dietary methionine on the metabolites and enzymes of methionine metabolism in rat liver. Significant decreases in hepatic concentrations of betaine and serine occurred when the dietary methionine was raised from 0.3 to 1.0%. We observed increased concentrations of S-adenosylhomocysteine in livers of rats fed 1.5% methionine and of S-adenosylmethionine and methionine only when the diet contained 3.0% methionine. Methionine supplementation resulted in decreased hepatic levels of methyltetrahydrofolate-homocysteine methyltransferase and increased levels of methionine adenosyltransferase, betaine-homocysteine methyltransferase, and cystathionine synthase. We used these data to simulate the regulatory locus formed by the enzymes which metabolize homocysteine in livers of rats fed 0.3% methionine, 1.5% methionine, and 3.0% methionine. In comparison to the model for the 0.3% methionine diet group, the model for the 3.0% methionine animals demonstrates a 12-fold increase in the synthesis of cystathionine, a 150% increase in flow through the betaine reaction, and a 550% increase in total metabolism of homocysteine. The concentrations of substrates and other metabolites are significant determinants of this apparent adaptation.


Temporo-spatial cell-cycle kinetics in HeLa cells irradiated by Ir-192 high dose-rate remote afterloading system (HDR-RALS).
Intracavitary irradiation plays a pivotal role in definitive radiotherapy for cervical cancer, and the Ir-192 high dose-rate remote afterloading system (HDR-RALS) is often used for this purpose. Under this condition, tumor tissues receive remarkably different absorption doses, with a steep gradient, depending on distance from the radiation source. To obtain temporo-spatial information regarding cell-cycle kinetics in cervical cancer following irradiation by Ir-192 HDR-RALS, we examined HeLa cells expressing the fluorescence ubiquitination-based cell cycle indicator (Fucci), which allowed us to visualize cell-cycle progression. HeLa-Fucci cells, which emit red and green fluorescence in G1 and S/G2/M phases, respectively, were grown on 35-mm dishes and irradiated by Ir-192 HDR-RALS under normoxic and hypoxic conditions. A 6 French (Fr) catheter was used as an applicator. A radiation dose of 6 Gy was prescribed at hypothetical treatment point A, located 20 mm from the radiation source. Changes in Fucci fluorescence after irradiation were visualized for cells from 5 to 20 mm from the Ir-192 source. Several indices, including first green phase duration after irradiation (FGPD), were measured by analysis of time-lapse images. Cells located 5 to 20 mm from the Ir-192 source became green, reflecting arrest in G2, in a similar manner up to 12 h after irradiation; at more distant positions, however, cells were gradually released from the G2 arrest and became red. This could be explained by the observation that the FGPD was longer for cells closer to the radiation source. Detailed observation revealed that FGPD was significantly longer in cells irradiated in the green phase than in the red phase at positions closer to the Ir-192 source. Unexpectedly, the FGPD was significantly longer after irradiation under hypoxia than normoxia, due in large part to the elongation of FGPD in cells irradiated in the red phase. Using HeLa-Fucci cells, we obtained the first temporo-spatial information about cell-cycle kinetics following irradiation by Ir-192 HDR-RALS. Our findings suggest that the potentially surviving hypoxic cells, especially those arising from positions around point A, exhibit different cell-cycle kinetics from normoxic cells destined to be eradicated.


Isotype specificity of antigen-specific helper clone in vivo.
Inoculation of an immortalized clone of radiation leukemia virus (RadLV)-transformed antigen (ovalbumin, OVA)-specific T cells together with the relevant carrier (OVA) into unprimed syngeneic mice results in a preferential increase in the expression of anti-OVA antibodies of the immunoglobulin (Ig)G2b and IgG2a isotypes. Identical boosting of the clone-primed mice further augments the preferential production of anti-OVA antibodies of these two isotypes. The class-related helper activity is not due to nonspecific shift of class expression produced by the injected tumor cells, as a non-helper clone of RadLV-transformed T cells does not change the isotypic pattern of anti-OVA antibodies in the inoculated mice. A carrier-specific activation of the B cells is responsible for the class-restricted function of the helper clone. The isotypic profile of anti-hapten antibodies in mice injected with 2,4-dinitrophenyl (DNP)-bovine serum albumin and OVA-specific helper clone is not altered. On the other hand, mice inoculated with the OVA-specific helper clone and DNP-OVA respond with a preferential elevation of anti-DNP antibodies of the IgG2a and IgG2b isotypes. The preferential class augmentation may result from carrier-specific signals delivered by the helper clone which activate B cells in vivo toward certain CH expression. Alternatively, the observed class pattern may be induced by an isotype noncommited helper clone which triggers selected population of B lymphocytes of defined differentiation status toward secretion of a restricted array of isotypes. Regardless of the mechanism of the clone-dependent class expression, the isotypic profile in most of the experiments clearly demonstrates that an antigen-specific helper clone may be one of the elements which regulates the class of antibodies to be produced in vivo under normal physiologic conditions.


An Unusual Hydrops Fetalis Associated with Compound Heterozygosity for Krüppel-like Factor 1 mutations.
Hydrops fetalis is commonly due to Hb Bart's (γ4) disease in South East Asia. Here, we report an unusual case of hydrops fetalis due to congenital dyserythropoietic anemia (CDA) associated with compound heterozygosity for Krüppel-like factor 1 (KLF1) gene mutations. Fetal cardiomegaly was first detected on routine mid-trimester scan in a pregnant woman with normal mean corpuscular volume (MCV) and Rhesus positive status. The fetus subsequently developed hydrops fetalis, and cordocentesis showed severe fetal anemia with a hemoglobin (Hb) level of 3.4 g/dL. Common causes of fetal anemia including Hb Bart's disease, parvovirus infection, and red cell antibodies were excluded. In view of the marked increase in erythroblasts at various stages of erythropoiesis, the diagnosis of CDA was suspected. We screened the couple for previously reported KLF1 gene mutations, showing that the mother was heterozygous for the c.525_526insCGGCGCC, p.Gly176Argfs*179 mutation, and her husband heterozygous for c.1012C>A, p.Pro338Thr mutation. The fetus was a compound heterozygote for these two KLF1 mutations. After counseling, repeated intrauterine transfusions were given at 27, 29, and 34 weeks' gestation; the hydrops fetalis was resolved. The baby was delivered at 34 weeks' gestation and required monthly blood transfusions but was otherwise thriving. Bone marrow aspiration at 10 months of age showed the features of ineffective erythropoiesis, compatible with CDA. In conclusion, hydrops fetalis can rarely be due to CDA associated with a compound heterozygous mutation for KLF1 gene mutations, and be managed by repeated intrauterine transfusions. Our present report adds to the wide clinical spectrum of KLF1 mutations.


The relationship between serum levels of total bilirubin and coronary plaque vulnerability.
Previous studies have reported that serum total bilirubin provides some protection against coronary artery disease (CAD); however, the relationship between serum levels of total bilirubin and culprit/target plaque vulnerability in patients with CAD remains unclear. In this study, we investigated the association between total bilirubin and tissue characterization of coronary plaque in patients with CAD. We enrolled 85 consecutive patients with CAD who underwent coronary angiography and intravascular ultrasound analyses [45 with acute coronary syndrome (ACS); 40 with stable angina pectoris (SAP)], and 45 age-matched participants served as the control group. Serum levels of total bilirubin in all participants were measured. The stability of the coronary plaque was compared between the ACS group and the SAP group, and the relationship between serum levels of total bilirubin and the features of coronary plaque was analyzed. Serum levels of total bilirubin in the ACS group were significantly lower than those in the SAP and control groups (P<0.01). Serum levels of total bilirubin were positively associated with fibrous plaques (r=0.386, P<0.001), whereas they were negatively associated with plaque burden (r=-0.413, P<0.001), lipid plaque (r=-0.419, P<0.001), and remodeling index (r=-0.275, P<0.05). Furthermore, an independent association between serum levels of total bilirubin and lipid-rich plaques (odds ratio, 0.78; 95% confidence interval, 0.64-0.95) was observed. Serum total bilirubin levels were found to be inversely associated with coronary plaque vulnerability, and decreased serum levels of total bilirubin may be an important factor for coronary lipid plaque formation, which contributes to the pathogenesis of CAD.


Efficacy of Second-line Tyrosine Kinase Inhibitors in the Treatment of Metastatic Advanced Non-small-cell Lung Cancer Harboring Exon 19 and 21 EGFR Mutations.
Background: Although superior clinical benefits of first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the treatment of advanced non-small-cell lung cancer (NSCLC) had been reported with different sensitivity, the sensitivity of second-line TKIs in NSCLC patients with different EFGR mutations was unknown. The purpose of this study is to investigate the clinical outcome of second-line EGFR-TKIs in the treatment of NSCLC patients according to different EGFR genotypes. Methods: The treatment outcomes of 166 NSCLC patients with different EGFR mutations treated by second-line TKIs were retrospectively reviewed. The efficacy was evaluated with Pearson chi-square or Fisher's exact tests, Log-rank test and Cox proportional hazards model. Results: The disease control rate (DCR) and objective response rate (ORR) of enrolled NSCLC patients were 77.7% and 11.4%, respectively. The exon 19 deletion group had a significantly longer median progression-free survival (PFS) (6.7 vs. 4.5 months, P=0.002) and overall survival (OS) (13.7 vs. 11.7 months, P=0.02) compared with the exon 19 L858R mutation group for NSCLC patients, as well for patients with brain metastasis [PFS: (6.7 vs. 3.9 months, p<0.001), OS: (13.7 vs. 7.9 months, p=0.006)]. No significant difference on PFS and OS was observed between exon 19 deletion and L858R mutation group for patients with bone metastasis. EGFR genotype and ECOG PS were independent predictors of PFS. Never smoking, exon 19 deletion, EGOC PS (0-1) and no brain metastasis were correlated with longer OS. No significant difference on side effect between exon 19 and 21 mutation group was observed. Conclusions: NSCLC patients harboring exon 19 deletion achieved better PFS and OS than those with L858R mutation, indicating that EGFR mutation is a significant prognostic factor for advanced NSCLC patients with and without brain metastasis receiving second-line EGFR-TKIs treatment.


Ocular emergencies: a quick reference.
Sight is precious, considered by many to be the most essential of the five senses. Children's eyesight is especially important, because good vision is related to learning. Regular eye examinations are needed to maintain proper eye health, since some serious eye disorders produce no early warning symptoms. Although prevention is the best defense, eye problems or injuries still occur suddenly and unexpectedly. When they do, recognizing their signs and symptoms and knowing what to do is vital to preserving sight.


Utility of prophylactic closed suction drainage in open reduction and internal fixation for tibial plateau fracture.
The usefulness of closed suction drains (CSD) after open reduction and internal fixation (ORIF) of tibial plateau fractures is a contested topic. The purpose of this study was to examine the impact of CSD in postoperative outcomes after tibial plateau fracture. Data were retrospectively collected from patients who underwent primary repair of closed tibial plateau fractures via an anterolateral approach between June 2021 to May 2022 at a single academic center. Fifty-six patients were included and 28 received CSDs at time of surgery. P values less than 0.05 were considered significant. Fifty-six patients were included. There was no significant difference in demographics, pre- and post-op hemoglobin, estimated blood loss during surgery, length of stay, postoperative MMEs and pain at 3 month follow-up, deep vein thrombosis (DVT), compartment syndrome, flexion contracture, use of incisional vac, infection rate, wound drainage, hematoma, neurologic pain, dehiscence, additional surgery, or range of motion at 3 months follow-up. We noted a significant difference in Defense and Veterans Pain Rating Scale (DVPRS) on POD1, demonstrating greater pain in those in the CSD group. Our findings suggest that the use of CSD in ORIF of tibial plateau fractures may not be of significant prophylactic benefit. CSDs in ORIF patients were associated with increased early postoperative pain and had no identifiable benefits. III.


Mental and somatic symptoms related to suicidal ideation in patients visiting a psychosomatic clinic in Japan.
Patients with suicidal ideation (SI) have various mental or somatic symptoms. A questionnaire-based interview elicited details concerning mental and somatic symptoms in patients visiting a psychosomatic clinic in Japan. Univariate logistic regression analyses followed by multiple regression models using a stepwise method were selected for identifying the candidate symptoms. Overall, symptoms related to depression were associated with SI in both sexes. Although women showed more various somatic symptoms associated with SI than men, many of those associations were diminished once severity of the depression was controlled. The current results suggest that a variety of self-reported symptoms, mainly related to depression, might reveal suicidal risk in outpatients with an urban hospital clinical setting.


Epoxyeicosatrienoates are the dominant eicosanoids in human lungs upon microbial challenge.
Lipoxygenase, cyclo-oxygenase and cytochrome P450 (CYP) products of arachidonic acid (AA) are implicated in pulmonary vasoregulation. The CYP-mediated epoxyeicosatrienoates (EETs) have been described previously as the predominant eicosanoids in human lungs upon stimulation with the Ca(2+) ionophore A23187. In this study, we challenged perfused human lungs with two microbial agents: Escherichia coli haemolysin (ECH) and formyl-methionyl-leucyl-phenylalanine (fMLP). Both stimuli elicited pronounced generation of leukotrienes (LTs), hydroxyeicosatetraenoic acids (HETEs), prostanoids (PTs) and EETs/dihydroxyeicosatrienoic acids (DHETs), as assessed by liquid chromatography-mass spectrometry, paralleled by pulmonary artery pressor response and lung oedema formation. The maximum buffer concentrations of EETs/DHETs surpassed those of LTs plus HETEs and PTs by a factor of four (ECH) or three (AA/fMLP). Dual 5-lipoxygenase/cyclo-oxygenase inhibition caused pronounced reduction of AA/fMLP-induced LT/PT synthesis and oedema formation but only limited attenuation of pulmonary vasoconstriction, while inhibition of CYP epoxygenase clearly attenuated AA/fMLP-induced EET/DHET synthesis and vasoconstriction but not oedema formation, suggesting a major contribution of LTs/PTs to vascular leakage and of EETs/DHETs to pressor response. Consequently, generation of EETs/DHETs is greater than that of LTs plus HETEs and PTs in ex vivo perfused human lungs upon microbial challenge suggesting a substantial contribution of these mediators to inflammatory-infectious pulmonary injury.


Impact of Traditional Healers on the HIV Care Cascade in Senegal, West Africa: A Longitudinal Study.
Consultation with traditional healers (THs) is common among people living with HIV in sub-Saharan Africa. We conducted a prospective longitudinal study to determine the association between consultation with THs and HIV outcomes following 12 months of antiretroviral therapy (ART). HIV-infected individuals presenting for care and initiation of ART in Dakar and Ziguinchor, Senegal were eligible for enrollment. Data were collected using interviews, clinical evaluations, laboratory analyses, and chart reviews at enrollment, 6 months after ART initiation, and 12 months after ART initiation. Among the 186 participants, 35.5% consulted a TH. The most common reason for consulting a TH was "mystical" concerns (18%). Those who consulted a TH before ART initiation were more likely to present with a CD4 count < 200 cells/mm3 (44% versus 28%; P = 0.04) and WHO stage 3 or 4 disease (64% versus 46%; P = 0.03), and they were less likely to disclose their HIV status (44% versus 65%; P = 0.04). Those who consulted a TH more than 6 months after ART initiation were more likely to report poor adherence to ART (57% versus 4%; P < 0.01). The strongest predictor of virologic failure was consulting a TH more than 6 months after ART initiation (odd ratio [OR], 7.43; 95% CI, 1.22-45.24). The strongest predictors of mortality were consulting a TH before ART initiation (OR, 3.53; 95% CI, 1.25-9.94) and baseline CD4 count < 200 cells/mm3 (OR, 3.15; 95% CI, 1.12-8.89). Our findings reveal multiple opportunities to strengthen the HIV care cascade through partnerships between THs and biomedical providers. Future studies to evaluate the impact of these strategies on HIV outcomes are warranted.


A Comparison of Psychological Symptoms in Survivors of Sex and Labor Trafficking.
Human trafficking is a form of interpersonal trauma that has significant mental health impacts on survivors. This study examined psychological symptoms in 131 survivors of sex and labor trafficking, including people trafficked into or within the United States. High rates of depression (71%) and posttraumatic stress disorder (PTSD) (61%) were identified. Two thirds of survivors also met criteria for multiple categories of Complex PTSD (C-PTSD), including affect dysregulation and impulsivity; alterations in attention and consciousness; changes in interpersonal relationships; revictimization; somatic dysregulation; and alterations in self-perception. Although there were not significant differences in the prevalence rates of diagnoses of PTSD or depression between survivors of sex and labor trafficking, important group differences were identified. Compared to survivors of labor trafficking, sex trafficking survivors had higher prevalence rates of pre-trafficking childhood abuse and a higher incidence of physical and sexual violence during trafficking. They reported more severe post-trauma reactions than labor trafficking survivors, including more PTSD and C-PTSD symptoms. They were also more likely to meet criteria for comorbid PTSD and depression, while labor trafficking survivors were more likely than sex trafficking survivors to meet criteria for depression alone. An analysis of gender differences found that trafficking survivors who identified as transgender endorsed more PTSD and C-PTSD symptoms, than male or female survivors. Childhood abuse exposure was linked to PTSD and C-PTSD in trafficking survivors, and trafficking type was predictive of the number of trauma-related symptoms beyond the role of pre-trafficking child abuse. Implications for assessment and intervention with trafficking survivors are discussed.


A strategy for distinguishing modified peptides based on post-digestion 18O labeling and mass spectrometry.
The simultaneous identification of multiple different protein modifications, with or without known mass changes, is a challenging application of mass spectrometry. In this contribution, a strategy for distinguishing modified peptides within a large background of unmodified peptides was demonstrated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) analysis of cytochrome c (Cyt-c) modified with 4-hydroxy-2-nonenal (HNE), based on post-digestion 18O labeling. Labeling of control Cyt-c peptides obtained from in-solution or in-gel digestion with 18O, prior to mixing in the ratio of 1:1 with peptides derived from a modified sample, identified more HNE modifications than a method based on a known mass increment search (Isom AL, Barnes S, Wilson L, Kirk M, Coward L, Darley-Usmar V. J. Am. Soc. Mass Spectrom. 2004; 15: 1136), demonstrating the potential of this strategy to enhance the detection of modified peptides by mass spectrometry. A virtue of the strategy is that it obviates the need for isotopic labeling of the modifier, making the method applicable to the detection of modifications occurring in vivo. Additionally, this technique identified protease auto-cleavage peptides by their altered mass isotopomer distribution due to incomplete 18O exchange, and modified peptides containing 'protein carbonyls' by partial 18O exchange, allowing these peptides to be differentiated during data analysis.


Echocardiographic Evaluation of the Right Atrial Area Index in Dogs with Pulmonary Hypertension.
Right atrial area (RAA) is a prognostic factor in human patients with pulmonary arterial hypertension (PAH). Reference intervals for RAA have been described in healthy dogs. To evaluate RAA indexed to the body surface area in dogs with PAH as an indicator of right atrial size, PAH severity and right-sided congestive heart failure (R-CHF). A total of 119 client-owned dogs, 48 dogs with PAH and 71 control dogs. Prospective observational study. Pulmonary arterial hypertension was classified according to the tricuspid regurgitation pressure gradient (TRPG) as mild (36-50 mmHg), moderate (51-75 mmHg), or severe (>75 mmHg). The RAA index was calculated as the RAA divided by body surface area. The RAA index was higher in dogs with moderate PAH (13.3 cm2 /m2 ; range, 3.4-24.7 cm2 /m2 ) and severe PAH (12.1 cm2 /m2 ; range, 5.4-21.8 cm2 /m2 ) than in those with mild PAH (6.7 cm2 /m2 ; range, 4.8-10.7 cm2 /m2 ) or in controls (7.3 cm2 /m2 ; range, 4.2-10.2 cm2 /m2 ; P < 0.001). The RAA index was higher (P < 0.0001) in dogs with R-CHF (17.5 cm2 /m2 ; range, 12.7-24.7 cm2 /m2 ) compared to those without R-CHF (7.6 cm2 /m2 ; range, 4.4-19.4 cm2 /m2 ). The most accurate cutoff value of the RAA index to identify R-CHF was >12.3 cm2 /m2 (sensitivity, 100%; specificity, 89.5%). In dogs with PAH, severity of tricuspid regurgitation (TR) was the only independent predictor of RAA index based on multivariate analysis (P < 0.02). The RAA index can be used to evaluate right atrial size in dogs and may be more effective than TRPG in predicting R-CHF in dogs with PAH. The severity of TR is the main determinant of the RAA index in dogs with PAH.


The complete mitochondrial genome of Mesogobio lachneri (Cypriniformes: Gobionidae) from Northeast Asia.
Although Mesogobio lachneri is the type species of the genus Mesogobio, its systematic position and status have remained unresolved to date. In this study, for the first time, we report the complete mitochondrial genome of M. lachneri using Sanger sequencing. It is a circular genome with a length of 16,602 bp, comprising 22 tRNAs, 13 protein-coding genes (PCGs), two rRNAs, and one non-coding control region. Our phylogenetic analysis reveals that M. lachneri is the close relative of the genus Gobio, indicating that Mesogobio may be a valid genus.


Emotional factors and subjective quality of life in subjects with spinal cord injuries.
To compare depression, subjective perception of quality of life, and social support in patients with spinal cord injuries 4 yr or more after trauma vs. controls. The Rorschach inkblot method, the Diagnostic Interview Schedule Self-Administered, the Progressive Matrix 38, the Social Support Appraisals, and the Subjective Quality of Life Profile were used to assess 33 patients with spinal cord injuries and 33 matched controls. No significant difference was observed for levels of general intelligence and depressive disorders. Subjects with spinal cord injuries assessed the general subjective quality of life as satisfactory, with exceptions for sexuality, physical condition, leisure activities, and holidays. A high degree of satisfaction with medical staff and inward life was observed. Social support was perceived as positive. However, they presented emotional distress, deteriorating perceptions, extreme preoccupation with their bodies, and diffuse anxiety. Although quality of life as evaluated by the persons concerned was good, areas of their lives remained unsatisfactory and a source of mental suffering. The next stage would study the factors involved and the means needed to help these subjects improve these aspects of life.


ATPase strongly bound to higher eukaryotic ribosomes.
80 S ribosomes from a number of higher eukaryotic organisms are able to hydrolyse ATP and GTP without the addition of soluble protein factors. ATPase seems to be an intrinsic activity of the ribosome, as indicated by the findings that ATPase activity is not diminished upon dissociation of ribosomes and reassociation of subunits, by washing with 0.66 M (KCl + NH4Cl) or 0.6 M LiCl treatment and ethanol precipitation; 1.5 M LiCl treatment removes only 40% ATPase activity. 80 S ribosomes are able to bind a variety of NTPs, NDPs and NTP analogues, with a preference for ATP. Effective inhibitors of the ribosomal ATPase are ammonium metavanadate and alcaloid emetine. The ATPase activity is present on both ribosomal subunits, which may reflect the existence of two catalytical sites for ATP on the 80 S ribosome. Ribosomal ATPase is stimulated by the occupancy of the A site, in particular with charged tRNA. The ATPase inhibitor adenylylimidodiphosphate almost completely prevents elongation-factor(EF)-1-dependent binding of Phe-tRNA(Phe) to the A site. The hydrolysis of ATP, therefore, is likely to be involved in the mechanism of tRNA binding to the A site of the 80 S ribosome. As far as wide substrate specificity and possible participation in tRNA interaction with the ribosome are concerned, the ribosomal ATPase seems to be similar to EF-3 found in fungi. A synergism in ATPase activities of yeast EF-3 and rabbit liver ribosomes at high ATP concentration and certain ribosome/EF-3 ratios have been observed. Rabbit liver ribosomes seem to stimulate the ATPase activity of yeast EF-3 similar to the mechanism in yeast ribosomes, though less efficiently.


Genomic convergence toward diploidy in Saccharomyces cerevisiae.
Genome size, a fundamental aspect of any organism, is subject to a variety of mutational and selection pressures. We investigated genome size evolution in haploid, diploid, and tetraploid initially isogenic lines of the yeast Saccharomyces cerevisiae. Over the course of approximately 1,800 generations of mitotic division, we observed convergence toward diploid DNA content in all replicate lines. This convergence was observed in both unstressful and stressful environments, although the rate of convergence was dependent on initial ploidy and evolutionary environment. Comparative genomic hybridization with microarrays revealed nearly euploid DNA content by the end of the experiment. As the vegetative life cycle of S. cerevisiae is predominantly diploid, this experiment provides evidence that genome size evolution is constrained, with selection favouring the genomic content typical of the yeast's evolutionary past.


Current techniques for vesicovaginal fistula repair: surgical pearls to optimize cure rate.
Vesicovaginal fistulas (VVFs) are a devastating consequence of prolonged labor in developing countries and pelvic surgery in developed countries. Clinical history, physical examination, and pertinent radiographic studies are necessary for proper diagnosis. Endoscopic management can lead to successful closure of small fistulas; the advent of tissue bioglues has made this modality more promising. However, the majority of patients will require transvaginal or transabdominal repair of the fistula. This article reviews the basic principles of fistula closure and discusses adjuvant techniques with tissue interposition grafts; techniques for successful closure of fistulas; and newer modalities for repair using tissue bioglues, laparoscopy, and robotic surgery.


Mitochondrial oxidative enzyme activity in individual fibre types in hypo- and hyperthyroid rat skeletal muscles.
Quantitative cytochemical and biochemical techniques have been used in combination to study the response of mitochondrial oxidative enzymes in individual muscle fibre types to hypo- and hyperthyroidism. Hypothyroidism resulted in decreased activity of succinate dehydrogenase (SDH), L-glycerol-3-phosphate dehydrogenase (L-GPDH), and D-3-hydroxybutyrate dehydrogenase (D-HBDH) in all fibre types of both slow-twitch soleus and fast-twitch extensor digitorum longus (e.d.l.) muscles. In hyperthyroidism, only L-GPDH activity increased in e.d.l. but more marked increases were seen in soleus muscles, which also showed increased SDH activity. In addition to these alterations in the enzyme activity in individual fibre types the metabolic profile of the muscle is further modified by the hormone-induced interconversion of slow- to fast-twitch fibres and vice versa.


Counteranion-controlled water cluster recognition in a protonated octaamino cryptand.
Structural aspects of binding of water cluster and halides in the octaamino cryptand L (1,4,11,14,17,24,29,36-octaazapentacyclo[22.214.171.124.(6,9)2.(19,22)2(31,34)]tetratetraconta-6(43),7,9(44),19(41),20,22(42),31(39),32,34(40)-nonaene, N(CH2CH2NHCH2-p-xylyl-CH2NHCH2CH2)3N) in a protonated state were examined. Crystallographic results show binding of the acyclic quasiplanar water tetramer [H4L(H2O)4](I)4.2.57H2O (1) in a tetraprotonated cryptand L having an iodide counteranion, where two water molecules reside inside the two tren-based cavity, bridged by a third water molecule, and a fourth external water molecule is hydrogen bonded to the bridged water molecule. In the case of complexes [H6L(Br)][(Br)6H].4H2O.2HBr (2) and [H6L(Cl)][(Cl)6H].10.86H2O (3), a single bromide and chloride occupied, respectively, the inside of the cryptand cavity, where L is in a hexaprotonated state. Monotopic recognition of bromide/chloride was observed at the center of the cryptand cavity where halides show C-H...halide interactions instead of the N-H...halide interactions reported in the ditopic complexes of halides with the same cryptand, 5 and 6. Thermal analyses on 1-3 were carried out, and the data obtained distinctly differentiate water cluster complex 1 from the anion-encapsulated cryptates 2 and 3. This study represents the first example of anion-controlled cluster formation inside the cavity of a cryptand.


Stress Corrosion Cracking Behavior of Alloy 600 Coupled to Magnetite under High-Temperature Caustic Conditions.
This study aims to investigate and explain the magnetite-accelerated stress corrosion cracking phenomenon of Alloy 600 under caustic conditions, based on the electrochemical behavior. After the SCC test that lasted for 300 h, no cracks were observed in any of the magnetite-free specimens, whereas cracks with a depth of 150 to 280 μm were generated in all the magnetite-deposited specimens. Furthermore, the electrochemical behavior of magnetite and Alloy 600 demonstrated that Alloy 600 behaved as an anode in the coupling system with magnetite. In this coupling system, the electrochemical potential of Alloy 600 can be shifted into the range potentially susceptible to stress corrosion cracking.


Immediate mandibular rehabilitation with endosseous implants: simultaneous extraction, implant placement, and loading.
This report of a clinical patient series indicates the relative safety and illustrates the procedures involved in the extraction of remaining teeth followed by immediate implant placement and loading with a simple acrylic resin fixed denture. Ten consecutive patients who selected tooth extraction and implant-supported fixed denture rehabilitation of the mandible were treated using a 1-visit approach for extraction, implant placement, and restoration. Healthy individuals (10 women) were treated under local anesthesia. Fifty-four implants were placed in 10 patients. Five or 6 Astra Tech implants (11 or 13 mm long) were placed into the edentulous parasymphyseal region of the mandible. Four to 6 implants (48 of 54) were immediately loaded by the fabrication of a simple acrylic resin fixed denture. The criterion for loading was clinical judgment of primary stability, ie, the absence of axial or lateral mobility with physical resistance to rotation. Patients were recalled at 1, 3, and 12 weeks. At 12 weeks, impressions were made for the fabrication of a screw-retained fixed denture. The fixed dentures were completed using conventional fabrication and prosthetic techniques. After a period of 6 to 18 months, all 54 implants had survived and were considered 100% successful by independent testing of mobility and radiographic evidence of osseointegration. There were no surgical complications. Fracture and debonding of the acrylic resin provisional denture occurred for 1 patient during the first 12 weeks of treatment. Advantages to extraction with simultaneous replacement include the maintenance of vertical dimension, elimination of reline procedures and interim denture therapy, and potential improvement of soft tissue healing. This therapeutic approach simplifies patient care without apparent additional risk.


A meta-analysis of the effects of venlafaxine on anxiety associated with depression.
Venlafaxine is the first member of a novel class of antidepressants that inhibits the reuptake of both serotonin and norepinephrine. Clinical trials of venlafaxine have demonstrated its efficacy and safety in the treatment of patients diagnosed with major depression. Because patients who have depression also often have anxiety, recent investigations have focused on determining whether venlafaxine can relieve symptoms of anxiety in depressed patients. We performed a pooled analysis of six short-term trials of venlafaxine, retrospectively measuring anxiety in anxious depressed patients using the Hamilton Rating Scale for Depression (HAM-D), Anxiety/Somatization factor and Anxiety Psychic item scores. Three studies were placebo-controlled, and three were placebo- and active-drug-controlled; active controls were imipramine in two trials and trazodone in the third trial. Patients were categorized as having anxiety accompanying depression if baseline HAM-D Anxiety Psychic item scores were 2 or greater. Anxious depressed patients treated with venlafaxine showed greater improvement than those treated with placebo beginning at week 3, according to the HAM-D Anxiety/Somatization factor score, and beginning at week 1, according to the Anxiety Psychic item score. Both effects were maintained at week 6 of treatment (and at week 12 in the one study of longer duration). Finally, treatment with venlafaxine resulted in a highly significant (p < or = 0.001) improvement in depression scores in patients who were anxious at baseline, compared with placebo-treated patients. The results of this analysis demonstrate that venlafaxine is more effective than placebo in reducing symptoms of anxiety in depressed patients and suggest that venlafaxine may afford a monotherapy option for treating patients who have a comorbid diagnosis of depression with anxiety.


Overexpressed connective tissue growth factor in cardiomyocytes attenuates left ventricular remodeling induced by angiotensin II perfusion.
To evaluate the improving effects of specifically overexpressed connective tissue growth factor (CTGF) in cardiomyocytes on mice with hypertension induced by angiotensin II (AngII) perfusion, 24 transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) were divided into two equal groups that were perfused with acetic acid and AngII, respectively, for 7 days. Another 24 cage-control wild-type C57BL/6 mice (NLC) were divided and treated identically. Blood pressure was detected by caudal artery cannulation. Cardiac structural and functional changes were observed by echocardiography. Cardiac fibrosis was detected by Masson staining. After AngII perfusion, blood pressures of NLC and Tg-CTGF mice, especially those of the formers, significantly increased. Compared with NLC + AngII group, Tg-CTGF + AngII group had significantly lower left ventricular posterior wall thickness at end-diastole and left ventricular posterior wall thickness at end-systole as well as significantly higher left ventricular end-systolic diameter and left ventricular end-diastolic diameter (P < 0.05). Reverse transcription-polymerase chain reaction (RT-PCR) showed that Tg-CTGF + AngII group had significantly lower collagen I, α-SMA, and TGF-β mRNA expressions in cardiac tissues (P < 0.05). Tg-CTGF can protect AngII-induced cardiac remodeling of mice with hypertension by mitigating inflammatory response. CTGF may be a therapy target for hypertension-induced myocardial fibrosis, but the detailed mechanism still needs in-depth studies.


Genome-wide identification of the TCP gene family in Chrysanthemum lavandulifolium and its homologs expression patterns during flower development in different Chrysanthemum species.
TCP proteins, part of the transcription factors specific to plants, are recognized for their involvement in various aspects of plant growth and development. Nevertheless, a thorough investigation of TCPs in Chrysanthemum lavandulifolium, a prominent ancestral species of cultivated chrysanthemum and an excellent model material for investigating ray floret (RF) and disc floret (DF) development in Chrysanthemum, remains unexplored yet. Herein, a comprehensive study was performed to analyze the genome-wide distribution of TCPs in C. lavandulifolium. In total, 39 TCPs in C. lavandulifolium were identified, showing uneven distribution on 8 chromosomes. Phylogenetic and gene structural analyses revealed that ClTCPs were grouped into classes I and II. The class II genes were subdivided into two subclades, the CIN and CYC/TB1 subclades, with members of each clade having similar conserved motifs and gene structures. Four CIN subclade genes (ClTCP24, ClTCP25, ClTCP26, and ClTCP27) contained the potential miR319 target sites. Promoter analysis revealed that ClTCPs had numerous cis-regulatory elements associated with phytohormone responses, stress responses, and plant growth/development. The expression patterns of ClTCPs during capitulum development and in two different florets were determined using RNA-seq and qRT-PCR. The expression levels of TCPs varied in six development stages of capitula; 25 out of the 36 TCPs genes were specifically expressed in flowers. Additionally, we identified six key ClCYC2 genes, which belong to the class II TCP subclade, with markedly upregulated expression in RFs compared with DFs, and these genes exhibited similar expression patterns in the two florets of Chrysanthemum species. It is speculated that they may be responsible for RFs and DFs development. Subcellular localization and transactivation activity analyses of six candidate genes demonstrated that all of them were localized in the nucleus, while three exhibited self-activation activities. This research provided a better understanding of TCPs in C. lavandulifolium and laid a foundation for unraveling the mechanism by which important TCPs involved in the capitulum development.


Pressoreceptor modulation of renal but not splenic sympathetic reflexes.
Influences of sinoaortic and vagally innervated vascular pressoreceptors on excitatory splenic and renal sympathetic responses to splenic receptor stimulation were investigated in anesthetized cats. These experiments demonstrated that these pressoreceptors have little apparent effect on the magnitude of splenic nerve responses to splenic receptor stimulation by capsaicin, bradykinin, or congestion. In contrast, activation of these pressoreceptors attenuated renal nerve responses to splenic receptor stimulation. Influences of sinoaortic and vagally innervated receptors on tonic sympathetic nerve activity also were evaluated. Stimulation of these receptors by small increases in arterial pressure (15-21 mmHg) caused equivalent inhibition of splenic and renal nerve activity; large increases (50-66 mmHg) caused significantly greater inhibition of renal than splenic nerve activity. These results illustrate that excitatory renal and splenic sympathetic responses to splenic receptor stimulation are not suppressed equally by pressoreceptor activation, vascular pressoreceptors can have greater inhibitory influences on tonic renal than splenic nerve activity, and vascular pressoreceptor influences on sympathetic reflexes are similar to those on tonic nerve activity.


Hepatoprotective effect of ginsenoside Rb1 and compound K on tert-butyl hydroperoxide-induced liver injury.
The main component of Panax ginseng, which have been reported by many researchers, are ginsenoside Rb1, Rb2 and Rc. Orally administered ginsenosides are metabolized to 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (compound K) by intestinal bacteria and absorbed to blood. To understand its hepatoprotective effect and its mechanism, the effects of ginsenoside Rb1 and its metabolite compound K on chemically injured HepG2 cells and mice were investigated. Ginsenoside Rb1 and compound K were isolated from ginseng. Hepatotoxicity of HepG2 cells and mice was induced by tert-butyl hydroperoxide (t-BHP). Cytotoxicity for HepG2 cells and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for mice as markers of hepatoprotective activity were measured. Compound K protected HepG2 cell cytotoxicity induced by t-BHP. However, ginsenoside Rb1 did not inhibit cytotoxicity. Nevertheless, both ginsenoside Rb1 and compound K significantly inhibited the increment of ALT and AST induced by t-BHP in mice, when it was orally administered. However, intraperitoneally administered ginsenoside Rb1 did not inhibit the increment of plasma ALT and AST induced by t-BHP in mice. These compounds did not exhibit antioxidant activity. However, compound K showed the potent membrane stabilizing activity more than ginsenoside Rb1. Compound K, which was produced from ginsenosides of Panax ginseng in intestine, could protect liver injury.


Elevated levels of anti-heat shock protein antibodies in patients with cerebral ischemia.
One of the important mechanisms involved in the development of vascular lesions leading to ischemic stroke could be an immune response to heat shock proteins (hsp). For carotid atherosclerosis and myocardial infarction, an association with an increase in anti-hsp 65 antibodies has been demonstrated. The aim of our study was (1) to investigate whether ischemic stroke is associated with a humoral immune response to hsp; (2) to study the connection between anti-hsp antibodies and other stroke risk factors; (3) to estimate if the elevated levels of anti-hsp antibodies could be an independent risk factor for stroke. We examined 180 patients (in the first 48 h after stroke onset) and 64 age-matched healthy controls. The levels of IgG and IgM antibodies to hsp 65 and 70 were measured by ELISA. Ischemic stroke was connected with a significant elevation of anti-hsp 65 and anti-hsp 70 antibody levels (IgG and IgM) compared with controls (p < 0.0001). The multifactorial logistic regression analysis showed that increased levels of anti-hsp 65 and anti-hsp 70 IgG antibodies are independent risk factors for stroke. Our results suggest that humoral immunity to hsp is common in stroke patients and that elevated levels of anti-hsp antibodies could be triggering factors for stroke.


Kappa statistics in the screening of malignancy of prostate.
The optimal upper limit of the normal range for prostate specific antigen (PSA) is suggested, but review of literature reveals that, malignancy of prostate can occur below that range and some benign prostatic diseases are occasionally associated with higher levels. The aim of the study is for early detection of prostatic malignancy. We tried to evaluate digital rectal examination (DRE), estimation of PSA and transrectal ultrasound (TRUS) guided core needle biopsy and histopathological examination in the patients. Seventy-two consecutive patients with lower urinary tract symptoms were taken in this retrospective study from January 2005 to February 2006. PSA level was measured by automated chemilumininescence system. Prostatic biopsies were taken for histopathological examination and stained with haematoxylin and eosin. Gleason grading was applied in case of adenocarcinoma of prostate. For detection of malignancy, sensitivity, specificity, predictive value for positive test and of negative test, percentage of false negatives and false positives, p-values, confidence interval and kappa statistical calculations were done. It was found 19 cases with PSA level > 4 ng/ml had benign diseases of prostate and one person having PSA level < 4 ng/ml had adenocarcinoma of prostate. Seven DRE positive cases had benign disease of the prostate and 5 DRE negative patients had adenocarcinoma of prostate. When compared, serum total PSA value alone and combined PSA and DRE, the later combined approach was found to be more useful. We recommend the study of DRE, PSA and TRUS guided core needle biopsy for detection of prostatic cancer at localised and potentially curable stage.