Vascular Aging and Central Aortic Blood Pressure: From Pathophysiology to Treatment.
Large conductive arteries undergo to structural modifications by aging, eventually leading to increased vascular stiffness. As consequence, cardiovascular hemodynamic changes by increasing central blood pressure which may be also associated to the remodelling of peripheral resistance arteries that contribute to increase further the central vascular stiffness and blood pressure. These modifications resemble the ones that has been shown in essential hypertension, thus a condition of "early vascular aging" has been described in hypertensive patients. Since hypertension related target organs, particularly the heart, face aortic blood pressure rather than brachial blood pressure, it has been recently suggested that central blood pressure and other parameters of large arteries' stiffness, including pulse wave velocity (PWV), may better correlate with subclinical organ damage and might be useful to assess the cardiovascular risk of patients beyond the traditional risk factors. Different devices have been validated to measure central blood pressure and PWV, and are currently available for clinical use. The increasing application of these tools in clinical practice could improve the management of hypertensive patients by better defining the cardiovascular risk and address the antihypertensive therapy.


Cortical evoked potentials and somatosensory perception in chronic spinal cord injury patients.
The correlation between somatosensory evoked potentials (SEPs) and sensory perception was studied in 110 patients with traumatic chronic spinal cord lesions. Perception thresholds over the legs for light touch, vibratory sensibility, temperature and thermal pain were tested together with recordings of tibial and peroneal SEPs. Tibial nerve SEPs correlated better with sensory perception than peroneal nerve SEPs. Normal tibial nerve SEPs were not present with absent or trace vibratory sensibility and vice versa. However, we found many exceptions to the correlation between temperature and pain perception and SEPs. Light touch, vibratory sensibility, and SEPs were highly correlated between each other, while temperature and pain perception correlated poorly to these other modalities. This represents an evident segregation of touch perception, vibratory sensibility and SEPs, which are thought to share dorsal columns as a common ascending pathway, and temperature and pain perception known to be related to the spinothalamic system.


Caged oligonucleotides for bidirectional photomodulation of let-7 miRNA in zebrafish embryos.
Many biological functions of microRNA (miRNA) have been identified in the past decade. However, a single miRNA can regulate multiple gene targets, thus it has been a challenge to elucidate the specific functions of each miRNA in different locations and times. New chemical tools make it possible to modulate miRNA activity with higher spatiotemporal resolution. Here, we describe light-activated (caged) constructs for switching let-7 miRNA 'on' or 'off' with 365 nm light in developing zebrafish embryos.


Ion mobility spectrometry and mass spectrometry coupled to gas chromatography for analysis of microbial contaminated cosmetic creams.
The most commonly used technique for monitoring microbial contamination in cosmetic products is plate counting. In this contribution, headspace - gas chromatography (HS-GC) coupled to mass spectrometry (MS) or ion mobility spectrometry (IMS) is proposed as a technique to evaluate rapidly and accurately the state of microbial colonies in cosmetic creams using the volatile organic compounds produced by microorganisms (MVOC). The work focuses on monitoring two of the microorganisms that most frequently occur in such creams, Candida albicans and Staphylococcus aureus. In addition, two different types of ingredient with antimicrobial properties (a chemical preservative and a natural preservative) were added to study the behaviour of these microorganisms under different conditions. The facial creams were elaborated and inoculated with the two above microorganisms, and then sampled weekly for 4 weeks, analysing the evolution of the MVOCs by HS-GC-MS and HS-GC-IMS. In addition, microbial contamination was determined by the classical plate counting method. The pH, colour, viscosity and water activity parameters were also measured. The use of chemometric tools is essential because of the large amount of data generated, and different models based on discriminant analysis with an orthogonal projection on latent structures (OPLS-DA) were constructed. The optimal models obtained by both analytical techniques allowed differentiation between contaminated and non-contaminated creams, with a validation success rate of 94.4%. In addition, MVOC monitoring also allowed assessment of the microbial concentration.


The epidemiology of good nutritional status among children from a population with a high prevalence of malnutrition.
To identify socio-economic demographic and environmental factors that predict better height-for-age for children under 5 years of age in a Dhaka slum population. A panel survey, conducted between 1995 and 1997. A random sample of households was selected. Socio-economic, demographic and environmental variables were collected monthly by questionnaire and nutritional status was assessed. Dhaka slums in Bangladesh. Three hundred and ninety-two children, surveyed in September-November 1996. Height-for-age Z-score (HAZ) above -2. Thirty-one per cent of children had HAZ >-2. Logistic regression adjusted for cluster sampling showed that better nourished children were more likely to have taller mothers, to be from female-headed households and from families with higher income, electricity in the home, better latrines, more floor space and living in Central Mohammadpur. Better nourished children were less likely to have fathers who have taken days off from work due to illness. CONCLUSIONS Interest in 'positive deviance' is motivated by the recognition that a focus on the malnourished only--the bottom tail of the distribution--provides indications of how families fail, but not of how they succeed in maintaining child nutrition in the face of adversity. Our analysis provides an alternative perspective on nutrition and vulnerability in an urban slum setting.


Tissue-specific activation of a cloned alpha-fetoprotein gene during differentiation of a transfected embryonal carcinoma cell line.
To identify cis-acting DNA elements involved in the activation of the alpha-fetoprotein gene during differentiation, modified copies of the gene were introduced into murine F9 embryonal carcinoma cells. The differentiation of the transformants to either parietal or visceral endoderm was accompanied by induction of the exogenous template in a manner qualitatively, but not quantitatively, identical to that of the endogenous alpha-fetoprotein gene.


Studying the Translatome with Polysome Profiling.
Polysome fractionation by sucrose density gradient centrifugation followed by analysis of RNA and protein is a technique that allows to understand the changes in translation of individual mRNAs as well as genome-wide effects on the translatome. Here, we describe the polysome profiling technique and RNA as well as protein isolation procedures from sucrose fractions.


Application of microwave and ohmic heating for pasteurization of cantaloupe juice: microbial inactivation and chemical properties.
Cantaloupe melon (Cucumis melo L.) is one of the most important dessert fruits and is cultivated in many countries of the world. The effects of microwave (400 and 800 W for 110 s), ohmic (100 and 200 V for 110 s) and conventional heating (27-75 °C for 30 min) treatments on inactivation of Escherichia coli, Salmonella Typhimurium, S. Enteritidis and Staphylococcus aureus pathogens; pH and degradation of vitamin C, β-carotene and phenolic compounds of cantaloupe juice were investigated. As time passed, all of the treatments resulted in significant (P ≤ 0.05) decreases in the number of pathogens and vitamin C, β-carotene and phenolic compound content, whereas the pH of samples did not show significant changes. The mentioned parameters were more reduced by increasing the power, voltage and temperature of ohmic, microwave and conventional heating treatments, respectively. Comparison of the results for conventional heating with those of ohmic and microwave heating revealed that the complete inactivation time of pathogens by the two latter treatments was much shorter than that of the former. After 20 s, the effect of ohmic heating at 200 V on decreasing vitamin C content was significantly (P ≤ 0.05) higher than that of the other treatments. The amounts of β-carotene and phenolic compounds showed the most reduction under 800 W microwave treatment. The results obtained for conventional, ohmic and microwave heating treatments indicated a higher degradation of β-carotene and phenolic compounds and a lower loss of vitamin C in the former. © 2019 Society of Chemical Industry.


Physical Health Problems and Barriers to Optimal Health Care Among Children in Foster Care.
Children and adolescents in foster care placement represent a unique population with special health care needs, often resulting from pre-placement early adversity and neglected, unaddressed health care needs. High rates of all health problems, including acute and/or chronic physical, mental, and developmental issues prevail. Disparities in health status and access to health care are observed. This article summarizes the physical health problems of children in foster care, who are predisposed to poor health outcomes when complex care needs are unaddressed. Despite recognition of the significant burden of health care need among this unique population, barriers to effective and optimal health care delivery remain. Legislative solutions to overcome obstacles to health care delivery for children in foster care are discussed.


Palliative care in onco-hematology: a perspective.
Palliative care (PC) is focused on individualized symptomatic control, psychological help, and support in the context of severe disease. Oncologic patients are still the most referred to PC and hematologic patients are only 7%. This is a commentary about PC applied to hematologic patients. There is evidence supporting that these patients behave as a special group in PC when compared with other tumors: there is a smaller number of referrals, with more advanced disease status, more symptomatology expressed, and less time between the last treatment date and the referral date or death. This article also expresses the experience of an oncologic palliative care unit. More health education programs in PC are needed for specialized professionals in hematology, as well as a change of nowadays health politics, in order to increase the participation of this specialized care in hematology.


Evaluating peritoneal fluid transport in continuous peritoneal dialysis patients: a practical approach.
Evaluating the peritoneal fluid kinetics is of clinical importance in peritoneal dialysis treatment. We have previously developed a simple way to evaluate the peritoneal fluid transport characteristics in continuous ambulatory peritoneal dialysis patients which, however, cannot be applied to those patients on a fixed dialysis schedule. Therefore, in the present study, we tested the possibility to vary the peritoneal dwell time and tried to develop a more patient-friendly ultrafiltration (UF) collection protocol. The patients' UF volume was recorded for 10 days. All patients recruited were asked to perform their usual dialysis exchanges with, however, a special UF data collection protocol to improve the accuracy of computer simulation: at least one dwell of 2-4 h, one of 4-7 h, and one of more than 7 h. The fluid transport model was applied to the pooled UF volume for fluid kinetics simulation, and the data from the following day's UF records using the same glucose concentration and dwell time were used to evaluate reliability and accuracy of the simulated UF value. Fifty-two chronic peritoneal dialysis patients were included in the present study. All of the UF data could be used in the computer simulation, and there was a significant negative correlation between fluid absorption rate (K(e); see text) and actual UF volume on the following day using a glucose concentration of 1.5% and a dwell time of 4 h (r = -0.336, p < 0.05). The estimated UF values correlated significantly with the actually measured UF values. The variability of the results, expressed by the width between the 95% limits of agreement, fell within -139.2 to 131.9 ml, while the mean difference was -3.7 ml. Our present study showed that varying the peritoneal dwell time was a patient-friendly UF data collection protocol for continuous ambulatory peritoneal dialysis patients on a fixed dialysis schedule. Applying the fluid transport model and nonlinear least squares regression analysis to pooled UF values might be a good and simple way to predict the peritoneal UF capacity.


Mechanism of action of ATP on intestinal epithelial cells. Cyclic AMP-mediated stimulation of active ion transport.
ATP, ADP and AMP but not adenosine increased cyclic AMP in dispersed enterocytes prepared from guinea pig small intestine. This action of ATP was augmented by IBMX and was reproduced by App(NH)p or App(CH2)p. ATP also increased the formation of cyclic [14C]AMP in enterocytes that had been preincubated with [14C]adenine. Gpp(NH)p and NaF each caused persistent activation of adenylate cyclase in plasma membranes from enterocytes and ATP caused significant augmentation of this persistent activation. In addition to increasing cellular cyclic AMP and augmenting Gpp(NH)p and NaF-stimulated persistent activation of adenylate cyclase, ATP increased the Isc across mounted strips of small intestine and inhibited net absorption of fluid and electrolytes in segments of everted small intestine. These results indicate that intestinal epithelial cells possess a receptor that interacts with ATP and other adenine nucleotides and that receptor occupation by ATP causes activation of adenylate cyclase, increased cyclic AMP and changes in active ion transport across intestinal mucosa.


Ecophysiological roles of abaxial anthocyanins in a perennial understorey herb from temperate deciduous forests.
Accumulation of abaxial anthocyanins is an intriguing leaf trait particularly common among deeply shaded understorey plants of tropical and temperate forests whose ecological significance is still not properly understood. To shed light on it, possible ecophysiological roles of abaxial anthocyanins were tested in the perennial understorey herb of temperate deciduous forests Saxifraga hirsuta, chosen as a model species due to the coexistence of green and anthocyanic leaves and the presence of an easily removable lower anthocyanic epidermis. Anthocyanins accumulated during autumn, which temporally matched the overstorey leaf fall. Patterns of development of abaxial anthocyanins and direct measurements of photochemical efficiency under monochromatic light were not consistent with a photoprotective hypothesis. Enhancement of light capture also seemed unlikely since the back-scattering of red light towards the lower mesophyll was negligible. Seed germination was similar under acyanic and anthocyanic leaves. A relevant consequence of abaxial anthocyanins was the dramatic reduction of light transmission through the leaf. The dark environment generated underneath the Saxifraga canopy was enhanced by the horizontal repositioning of leaves, which occurs in parallel with reddening. This might play a role in biotic interactions by inhibiting vital processes of competitors, which may be of especial importance in spring before the overstorey leaves sprout.


Does Provider Type Affect Bone Health Surveillance in Chronic Pancreatitis?
Bone density screening (DEXA) and vitamin D serum assay (Vit-D) are recommended in chronic pancreatitis, but adherence by providers is unknown. Assess DEXA/Vit-D testing according to provider type. A retrospective cohort study of chronic pancreatitis patients followed in a tertiary hospital (August 2017-2018) was conducted. Provider type was primary care (PCP), gastroenterologist, and pancreas specialist. Chi-square test and multivariable analysis were conducted to assess the relation between provider type and DEXA/Vit-D testing. Subset analyses were performed among patients with fecal elastase < 200 mcg/g. A total of 478 charts were reviewed, and 256 (53.6%) met diagnosis of chronic pancreatitis; 184 (71.9%) definite, 45 (17.6%) probable, and 27 (10.6%) borderline chronic pancreatitis. DEXA was tested in 112/256 (43%) patients; 16/57(28%) patients followed by PCP, 11/38 (28.9%) by gastroenterologists, and 85/161(52.2%) by pancreas specialists (p = 0.001). Vit-D was tested in 210/256 (82.0%) patients; 42/57(73.7%) followed by PCP, 29/38 (76.3%) by gastroenterologists, and 139/161(86.3%) by pancreas specialists (p = 0.06). Multivariate analysis assessing DEXA/Vit-D testing showed pancreas specialists were more likely to test compared to PCP (DEXA: OR 3.70, CI 1.77-7.74, p = 0.001. Vit-D: OR 3.24, CI 1.43-7.38, p = 0.005), but gastroenterologists were not. In patients with low fecal elastase, pancreas specialists were more likely to test DEXA (pancreas specialists: 62.1%, PCP: 40.0%, Gastroenterologists: 11.1%, p = 0.01) and all patients received Vit-D testing. Chronic pancreatitis patients often do not receive optimal preventive care. Pancreas specialists were more likely to perform DEXA and Vit-D testing compared to PCP and gastroenterologists. More physician education is needed.


Prevention of glucocorticoid-induced osteopenia: effect of oral 25-hydroxyvitamin D and calcium.
Twenty-four patients (9 M and 15 F, age range 51-82) with polymyalgia rheumatica receiving 6-methylprednisolone for a period of 9 months (16 mg/daily/two weeks, 14 mg/daily/two weeks, 12 mg/daily/1 month, 10 mg/daily/1 month, 8 mg/daily/1 month, 6 mg/daily/1 month and 4 mg/daily for the last four months) were randomly assigned to receive either 250HD3 (35 mcg/day for 25 days/month) (Group A) or placebo (Group B) in a double-blind study. All patients also received 500 mg elemental calcium daily. Before and at 3, 6 and 9 months ESR, tenderness on palpation and subjective pain were evaluated. At the same times, mineral metabolism parameters (serum calcium, phosphorus, alkaline phosphatase, 24-h urinary calcium, phosphate and 24-h hydroxyproline excretion) and radial bone mineral content (BMC) were evaluated. Activity indexes (ESR and clinical parameters) improved in both groups. Furthermore, serum alkaline phosphatase and 24-h hydroxyproline excretion decreased significantly only in Group A, and BMC decreased significantly in Group B but rose slightly in Group A. No side effects were observed in any of the patients.


Complete DiGeorge anomaly in the absence of neonatal hypocalcemia and velofacial and cardiac defects.
We report an atypical case of complete DiGeorge (DG) anomaly that presented initially exclusively as severe combined immunodeficiency (SCID). The child had severe infections at diagnosis, in keeping with the SCID phenotype; however, normal lymphocyte counts and immunoglobulin levels were noted at admission, which delayed diagnosis. Importantly, the child presented without neonatal hypocalcemia or velofacial or cardiac abnormalities at the time of diagnosis, which masked underlying DG. This case outlines the difficulties in making the diagnosis of SCID in a timely manner and illustrates the variation in presentation of the 22q11.2 deletion syndrome. There should be a high index of suspicion for primary immunodeficiency among children with severe infections and, because management may vary, DG anomaly should be considered in the differential diagnosis of T- B+ natural killer+ SCID.


Both lung recruitment maneuver and PEEP are needed to increase oxygenation and lung volume after cardiac surgery.
Patients ventilated after cardiac surgery commonly have impaired oxygenation, mainly due to lung collapse. We have previously found that PaO2 and end-expiratory lung volume (EELV) were increased by a lung recruitment maneuver (LRM) followed by positive end-expiratory pressure (PEEP). The aim of this study was to evaluate whether only PEEP or only a LRM could give similar effects. Thirty circulatory stable patients (aged 55-79 years) mechanically ventilated after cardiac surgery were randomized to receive LRM (four 10-s insufflations to an airway pressure of 45 cmH2O) and zero end-expiratory pressure (LRM-group), PEEP 12 cmH2O (PEEP-group) or LRM in combination with PEEP 12 cmH2O (LRM + PEEP-group). The set end-expiratory pressure was kept for 75 min. Before, during and after the intervention, EELV (SF6 washout technique) and blood gases were measured. Initial EELV and PaO2 were similar in all groups. In the LRM-group, PaO2 and EELV increased transiently (P < 0.0001), but returned at 5 min to the initial values. In the PEEP-group, PaO2 did not change but EELV increased to 155 +/- 27% of the initial value (P < 0.0001). In the LRM+PEEP-group, PaO2 and EELV increased to 212 +/- 66% and 178 +/- 31% of the initial values (P < 0.0001), respectively, and were maintained during PEEP application. In patients ventilated after cardiac surgery: (1) PEEP increased lung volume but not PaO2, (2) a lung recruitment maneuver without subsequent PEEP had no sustained effect, and (3) both a lung recruitment maneuver and PEEP were needed to increase and maintain the increased lung volume and PaO2.


Design of nematic liquid crystals to control microscale dynamics.
The dynamics of small particles, both living such as swimming bacteria and inanimate, such as colloidal spheres, has fascinated scientists for centuries. If one could learn how to control and streamline their chaotic motion, that would open technological opportunities in the transformation of stored or environmental energy into systematic motion, with applications in micro-robotics, transport of matter, guided morphogenesis. This review presents an approach to command microscale dynamics by replacing an isotropic medium with a liquid crystal. Orientational order and associated properties, such as elasticity, surface anchoring, and bulk anisotropy, enable new dynamic effects, ranging from the appearance and propagation of particle-like solitary waves to self-locomotion of an active droplet. By using photoalignment, the liquid crystal can be patterned into predesigned structures. In the presence of the electric field, these patterns enable the transport of solid and fluid particles through nonlinear electrokinetics rooted in anisotropy of conductivity and permittivity. Director patterns command the dynamics of swimming bacteria, guiding their trajectories, polarity of swimming, and distribution in space. This guidance is of a higher level of complexity than a simple following of the director by rod-like microorganisms. Namely, the director gradients mediate hydrodynamic interactions of bacteria to produce an active force and collective polar modes of swimming. The patterned director could also be engraved in a liquid crystal elastomer. When an elastomer coating is activated by heat or light, these patterns produce a deterministic surface topography. The director gradients define an activation force that shapes the elastomer in a manner similar to the active stresses triggering flows in active nematics. The patterned elastomer substrates could be used to define the orientation of cells in living tissues. The liquid-crystal guidance holds a major promise in achieving the goal of commanding microscale active flows.


Intraspecific variation in essential oil composition of the medicinal plant Lippia integrifolia (Verbenaceae). Evidence for five chemotypes.
The aerial parts of Lippia integrifolia (incayuyo) are widely used in northwestern and central Argentina for their medicinal and aromatic properties. The essential oil composition of thirty-one wild populations of L. integrifolia covering most of its natural range was analyzed by GC and GC-MS. A total of one hundred and fifty two terpenoids were identified in the essential oils. Sesquiterpenoids were the dominant components in all but one of the collections analyzed, the only exception being a sample collected in San Juan province where monoterpenoids amounted to 51%. Five clearly defined chemotypes were observed. One possessed an exquisite and delicate sweet aroma with trans-davanone as dominant component (usually above 80%). Another with an exotic floral odour was rich in oxygenated sesquiterpenoids based on the rare lippifoliane and africanane skeletons. The trans-davanone chemotype is the first report of an essential oil containing that sesquiterpene ketone as the main constituent. The absolute configuration of trans-davanone from L. integrifolia was established as 6S, 7S, 10S, the enantiomer of trans-davanone from 'davana oil' (Artemisia pallens). Wild plants belonging to trans-davanone and lippifolienone chemotypes were propagated and cultivated in the same parcel of land in Santa Maria, Catamarca. The essential oil compositions of the cultivated plants were essentially identical to the original plants in the wild, indicating that the essential oil composition is largely under genetic control. Specimens collected near the Bolivian border that initially were identified as L. boliviana Rusby yielded an essential oil practically identical to the trans-davanone chemotype of L. integrifolia supporting the recent view that L. integrifolia (Gris.) Hieron. and L. boliviana Rusby are synonymous.


The NDR/LATS protein kinases in neurobiology: Key regulators of cell proliferation, differentiation and migration in the ocular and central nervous system.
Nuclear Dbf2-related (NDR) kinases are a subgroup of evolutionarily conserved AGC protein kinases that regulate various aspects of cell growth and morphogenesis. There are 4 NDR protein kinases in mammals, LATS1, LATS2 and STTK8/NDR1, STK38L/NDR2 protein kinases. LATS1 and 2 are core components of the well-studied Hippo pathway, which play a critical role in the regulation of cell proliferation, differentiation, and cell migration via YAP/TAZ transcription factor. The Hippo pathways play an important role in nervous tissue development and homeostasis, especially with regard to the central nervous system (CNS) and the ocular system. The ocular system is a very complex system generated by the interaction in a very tightly coordinated manner of numerous and diverse developing tissues, such as, but not limited to choroidal and retinal blood vessels, the retinal pigmented epithelium and the retina, a highly polarized neuronal tissue. The retina development and maintenance require precise and coordinated regulation of cell proliferation, cell death, migration, morphogenesis, synaptic connectivity, and balanced homeostasis. This review highlights the emerging roles of NDR1 and NDR2 kinases in the regulation of retinal/neuronal function and homeostasis via a noncanonical branch of the Hippo pathway. We highlight a potential role of NDR1 and NDR2 kinases in regulating neuronal inflammation and as potential therapeutic targets for the treatment of neuronal diseases.


Spectral bounds on plasmon resonances for Ag and Au prolate and oblate nanospheroids.
Analytical expressions for the plasmon resonance frequencies of prolate and oblate spheroids and their dependence on ellipticity have been derived, and approximate bounds on these frequencies established. These formulas may be useful in tuning the plasmon resonance within certain limits. With increasing aspect ratio, the prolate spheroid resonance is red shifted relative to a sphere with no lower limit under the assumptions of a Drude dispersion model. On the other hand, the oblate resonances are blue shifted as the spheroid becomes increasingly flat, but up to a limit.


1,3-Dialkyl-8-(hetero)aryl-9-OH-9-deazaxanthines as potent A2B adenosine receptor antagonists: design, synthesis, structure-affinity and structure-selectivity relationships.
A number of 1,3-dialkyl-8-(hetero)aryl-9-OH-9-deazaxanthines were prepared and evaluated as ligands of recombinant human adenosine receptors (hARs). Several 1,3-dipropyl derivatives endowed with nanomolar binding affinity at hA(2B) receptors, but poor selectivity over hA(2A), hA(1) and hA(3) AR subtypes were identified. A comparison with the corresponding 7-OH- and 7,9-unsubstituted-deazaxanthines revealed that 9-OH-9-deazaxanthines are more potent hA(2B) ligands with lower partition coefficients and higher water solubility compared to the other two congeneric classes of deazaxanthines. An optimization of the para-substituent of the 8-phenyl ring of 9-OH-9-deazaxanthines led to the discovery of compound 38, which exhibited outstanding hA(2B) affinity (Ki=1.0 nM), good selectivity over hA(2A), hA(1) and hA(3) (selectivity indices=100, 79 and 1290, respectively) and excellent antagonist potency in a functional assay on rat A(2B) (pA(2B)=9.33).


Temperature dependence of D-glucose transport in reconstituted liposomes.
Sodium-dependent D-glucose uptake into proteoliposomes reconstituted from dimyristoylphosphatidylcholine (DMPC) and hog kidney brush border membrane extract is strongly affected by temperature and the physical state of the membranes. This dependence is defined by a nonlinear Arrhenius plot with a break point at 23 degrees C, a temperature not significantly different from the phase transition temperature of the pure lipid (24 degrees C). The transport process is characterized by different activation energies: 35.1 kcal/mol below and 5.5 kcal/mol above the transition temperature. The shift in the break point for the D-glucose transport activity from 15 degrees C, in the brush border membranes, to 23 degrees C in the reconstituted system leads us to conclude that the lipids surrounding the sodium/D-glucose cotransport system can exchange readily with the bulk lipid used for reconstitution. The results thus provide no evidence for the presence of an annulus of specific lipids surrounding the transport system.


Soybean- and olive-oils-enriched diets increase insulin secretion to glucose stimulus in isolated pancreatic rat islets.
Islets isolated from rats fed a lipid-enriched diet have shown an impairment of insulin secretion, but there is no available data comparing the effect of diet containing different dietary fat. This may be important in preventing or facilitating the establishment of diabetes. In this study, the effect of diets enriched (10%) with different fatty acids on insulin secretion by isolated pancreatic islets was investigated. The sources of the fatty acids tested were: saturated long chain from animal fat (AF), polyunsaturated from soybean oil (SO), and monounsaturated from olive oil (OL). The results were compared with those from rats receiving a diet enriched (10%) with a balanced mixture of fatty acids (the same proportion of AF, SO, and OL). The effect of fat-rich diets on insulin release was tested in vivo by giving a glucose load (glucose tolerance test-GTT) and in vitro in perfused islets. The mechanism involved was also examined by measuring 45Ca2+ and 86Rb+ fluxes, GLUT-2 content, and glucose oxidation in isolated islets. A significant increase of insulin secretion and glucose oxidation without any alteration of the ionic movements were detected in islets from SO and OL rats. GLUT-2 content was increased in islets of the OL group but diminished in AF rats. The results led us to postulate that soybean and olive oils may increase the response of insulin secretion to glucose stimulus in pancreatic islets.


Effect of Enteral Protein Amount on Growth and Health Outcomes in Very-Low-Birth-Weight Preterm Infants: Phase II of the Pre-B Project and an Evidence Analysis Center Systematic Review.
Adequate protein intake by very-low-birth-weight preterm infants (≤1,500 g at birth) is essential to optimize growth and development. The estimated needs for this population are the highest of all humans, however, the recommended intake has varied greatly over the past several years. A literature search was conducted in PubMed, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane Central databases to identify randomized controlled trials evaluating the effect of prescribed protein intake and identified outcomes. Articles were screened by 2 reviewers, risk of bias was assessed, data were synthesized quantitatively and narratively, and each outcome was separately graded for certainty of evidence. The literature search retrieved 25,384 articles and 2 trials were included in final analysis. No trials were identified that evaluated effect of protein amount on morbidities or mortality. Moderate certainty evidence found a significant difference in weight gain when protein intake of greater than 3.5 g/kg/day from preterm infant formula was compared with lower intakes. Low-certainty evidence found no evidence of effect of protein intake of 2.6 vs 3.1 vs 3.8 g/kg/day on length, head circumference, skinfold measurements, or mid-arm circumference. Low-certainty evidence found some improvement in development measures when higher protein intake of 3.8 vs 3.1 vs 2.6 g/kg/day were compared. Low-certainty evidence found no significant difference in bone mineral content when these protein intakes were compared. No studies were identified that compared protein intake greater than 4.0 g/kg/day. This systematic review found that protein intake between 3.5 and 4.0 g/kg/day promotes weight gain and improved development.


Antiretroviral therapies in pregnancy: maternal, fetal and neonatal effects. Swiss HIV Cohort Study, the Swiss Collaborative HIV and Pregnancy Study, and the Swiss Neonatal HIV Study.
Therapies containing two reverse transcriptase inhibitors (RTI) with or without protease inhibitors are used with increasing frequency in pregnant HIV-infected women. To assess the safety of antiretroviral therapy in pregnant women and their newborns. All clinical events and laboratory abnormalities in pregnant women on RTI with or without protease inhibitors and in their newborns were collected through an observational study. A total of 37 HIV-infected pregnant women have given birth to 30 children (by 30 April 1998). All received RTI, which were combined with protease inhibitors in 16 cases. Twelve women became pregnant while on treatment. Drugs used were as follows: zidovudine (n = 33), lamivudine (n = 33), stavudine (n = 4), indinavir (n = 9), ritonavir (n = 4), nelfinavir (n = 2) and saquinavir (n = 2). Adverse events during pregnancy were anaemia (n = 15), elevation of transaminases (n = 4), nausea/vomiting (n = 4), glucose intolerance (n = 2), nephrolithiasis (n = 2), diarrhoea (n = 2), hypertension (n = 1), insulin-requiring diabetes (n = 1). Adverse events in neonates were prematurity (n = 10), anaemia (n = 8), cutaneous angioma (n = 2), cryptorchidism (n = 2), transient hepatitis (n = 1). Non-life-threatening intracerebral haemorrhage occurred in a premature baby (33 weeks gestation) exposed during fetal life to zidovudine-lamivudine-indinavir, and in a term baby exposed to stavudine-lamivudine-indinavir. Extrahepatic biliary atresia occurred in one newborn exposed to zidovudine-lamivudine-indinavir. Maternal viral load was below 400 copies/ml in 18 out of 30 patients who delivered. One case of mother-to-child HIV transmission was identified. In HIV-infected pregnant women treated with two RTI with or without protease inhibitors, one or more adverse events occurred in 29 out of 37 women and in 14 out of 30 babies. In newborns, frequent prematurity, one case of biliary malformation and one intracerebral haemorrhage in a term baby are of concern. These observations do not preclude combination therapies during pregnancy but emphasize the necessity to maintain updated registers on their safety.


The "floppy diaphragm" sign with laparoscopic-associated pneumothorax.
Pneumothoraces in association with laparoscopy are uncommon and potentially disastrous complications that may also occur without adverse sequelae. The "floppy diaphragm sign" is a readily discernible and useful sign of a laparoscopic-induced pneumothorax. Tube thoracostomy is generally not indicated in stable patients as the pneumothorax typically resolves quickly upon desufflation of the pneumoperitoneum.


Full-endoscopic versus microscopic unilateral laminotomy for bilateral decompression of lumbar spinal stenosis at L4-L5: comparative study.
Full-endoscopic spine surgery for degenerative lumbar diseases is growing in popularity and has shown favourable outcomes. Lumbar endoscopic unilateral laminotomy for bilateral decompression (LE-ULBD) has been used to treat lumbar spinal stenosis (LSS). However, studies comparing LE-ULBD to microscopic ULBD are lacking. This study compared the clinical efficacy and radiological outcomes between the LE-ULBD and microscopic ULBD. The study retrospectively enrolled patients undergoing either LE-ULBD or microscopic ULBD for spinal stenosis at the L4-L5 level. The demographic data, operative details, radiological images, clinical outcomes, and complications of patients from the two groups were compared through matched-pairs analysis. The minimum follow-up duration was 24 months. There were 93 patients undergoing either LE-ULBD (n = 42) or microscopic ULBD (n = 51). The patient demographics were similar between the two groups. The LE-ULBD group had significantly less estimated blood loss, less analgesic use, and shorter hospitalization duration (P < .05). The endoscopic group had a significantly lower visual analog scale for back pain at all follow-up intervals compared with the microscopic group (P < .05). There were no significant differences in leg pain or Oswestry Disability Index. The cross-section area of the spinal canal was significantly wider after microscopic ULBD. There were no significant differences in post-operative degenerative changes in disc height, translational motion, or facet preservation rate. LE-ULBD is comparable in clinical and radiological outcomes with enhanced recovery for single-level LSS. The endoscopic approach might further minimize tissue injury and enhance post-operative recovery.


Apoptosis in the adult striatum after transient forebrain ischemia and the effects of ischemic severity.
The mechanisms of neuronal injury after cerebral ischemia have been under active investigation. The medium-size neurons in the dorsal striatum die within 24 h after transient cerebral ischemia. Using electron microscopy, the present study examined the nature of neuronal death in the striatum of adult rats following transient forebrain ischemia and tested the hypothesis that the ischemic severity might influence the nature of cell death. After severe ischemia (approximately 21 min ischemic depolarization), most neurons in the dorsal striatum died with swollen organelles and small irregular chromatin clumps resembling necrosis. The tissue damage in the dorsomedial striatum was less severe than that in the dorsolateral striatum and approximately 5% of the neurons in this region died with large chromatin clumps and relatively intact organelles resembling apoptosis. Some neurons displayed a mixture of necrotic- and apoptotic-like appearance. In contrast, the neurons with large somata only exhibited mild ultrastructural changes. After moderate ischemia (approximately 15 min ischemic depolarization), the tissue damage was less severe and the process of necrosis was temporally prolonged compared with that after severe ischemia. The apoptotic-like neuronal death was observed not only in the dorsomedial (approximately 6%) but also in the dorsolateral striatum (approximately 7%). The neurons in the striatum showed transient reversible changes after mild ischemia (approximately 10 min ischemic depolarization). The present study demonstrates that both apoptosis and necrosis occur in the adult striatum following transient forebrain ischemia and apoptosis occurs in the regions with less severe ischemia. These results suggest that ischemic severity might be one of the contributing factors to necrosis or apoptosis following transient global ischemia.


Reuniting Long Lost Cousins: a Novel Curriculum in Imaging Informatics for Clinical Informatics Fellows.
We developed a curriculum of imaging informatics for clinical informatics fellows. While imaging informatics and clinical informatics are related fields, they have distinct bodies of knowledge. The aim of this curriculum is to prepare clinical informatics fellows for questions regarding imaging informatics on the clinical informatics board certification examination, prepare fellows to handle issues and requests involving imaging informatics in their future roles as clinical informaticists, and develop sufficient knowledge and skills in order to interface with imaging and radiology domain experts. We mapped ACGME core competencies for clinical informatics and the clinical informatics skills and attributes to topics covered in this curriculum. Topics covered included orders vs. encounter-based workflow, understanding imaging informatics operations and the differences between an IT department leading digital image management and the radiology department, clinical decision support for radiology, procuring and integrating new modalities into a PACS system, troubleshooting slow application performance in a PACS environment, imaging sharing, artificial intelligence (AI) in imaging including AI bias, validation of models within home institution and regulatory issues, and structured reporting vs. Natural Language Processing to mine radiology report data. These topics were covered in interactive didactic sessions as well as a journal club. Future work will expand to include hands-on learning and a formal evaluation of this curriculum with current fellows and recent graduates.


Laparoscopic right hemicolectomy with D3 lymph node dissection for a patient with situs inversus totalis: report of a case.
Situs inversus totalis (SIT) is a rare congenital anomaly characterized by an inversion of the thoracic and abdominal viscera that creates a mirror image. The transposition of the organs imposes special demands on the diagnostic and technical skills of the surgeon, especially when performing laparoscopic surgery. We herein report the case of a 63-year-old man with colon cancer of the hepatic flexure who received a laparoscopic right hemicolectomy. Careful recognition by the surgeon of the mirror image anatomy and skillful use of his left hand resulted in a successful outcome. The surgery was not otherwise different from ordinary cases. Therefore, laparoscopic colectomy is considered to be a safe and feasible option for patients with colorectal cancer and SIT.


Bilateral gait asymmetry associated with tibiotalocalcaneal arthrodesis versus ankle arthrodesis.
Gait asymmetries have been reported following ankle arthrodesis. However, similar reports do not exist for tibiotalocalaneal arthrodesis (TTCA), which involves further articular fusion. This study aimed to assess the extent of gait asymmetry following TTCA when compared to ankle arthrodesis. Gait assessment was performed on 36 participants, including 12 ankle arthrodesis, 12 TTCA and 12 controls - using 3-D inertial sensors and pressure insoles. 48 gait parameters were monitored on both operated and non-operated sides. Questionnaires including AOFAS, FAAM, EQ-5D were used to assess both operative groups, comparatively. Both operative groups reported significantly smaller stride, slower walking speed, altered stance phase with longer loading and shorter push-off compared to controls. Joint range of motion was significantly reduced on the operated side of both operative groups at hindfoot, forefoot and toe intersegments. However, the ankle arthrodesis group reported a significantly higher alteration compared to controls in maximum contact force and pressure distribution. Furthermore, bilateral comparison showed extended gait asymmetry in the ankle arthrodesis group with 29 out of 48 parameters being significantly different between the two sides, whereas only 16 out of 48 gait parameters showed bilateral difference in the TTCA group. Both ankle salvage operations led to significant gait alteration and bilateral asymmetry. However, extended joint restriction in TTCA does not seem to worsen the gait outcomes. Further investigation is needed to understand the long-term impact of altered gait, on neighboring joints, following TTCA.


Flock-level risk factors for outbreaks of infectious arthritis in lambs, Norway 2018.
Outbreaks of infectious arthritis in young lambs associated with Streptococcus dysgalactiae subspecies dysgalactiae (SDSD) lead to reduced animal welfare, increased use of antibiotics and economic losses for sheep farmers. Understanding risk factors is essential when developing strategies to prevent such outbreaks. This questionnaire-based cross-sectional study classified sheep flocks of respondents as cases or controls. Flock-level risk factors for outbreaks of infectious arthritis were assessed using a multivariable logistic regression model. Eighty-four of 1498 respondents (5.6%) experienced an outbreak of infectious arthritis in their flock in 2018, the year of study. Factors associated with a higher risk of outbreak were larger flock size (OR 1.3, 95% CI 1.1-1.4, per 100 lambs), plastic mesh flooring in the lambing pen (OR 3.0, 95% CI 1.7-5.3) and a lambing percentage greater than 200 (OR 2.0, 95% CI 1.1-3.5). Flocks where farmers observed infections around the ear tags of lambs also had an increased risk of outbreak (OR 2.6, 95% CI 1.6-4.3). The risk factors identified in this study are characteristic of modern and intensively managed sheep farms in Norway. A distinguishing feature of Norwegian sheep farming is winter housing and indoor lambing. One might expect that this in itself is a risk factor because of high stocking densities during lambing. However, outbreaks of infectious arthritis in young lambs are reported by the industry to be a more recent phenomenon. The current study indicates that intensification of indoor management systems with larger flocks and higher production per ewe may predispose to outbreaks. The results provide a basis for further studies on transmission dynamics of SDSD in sheep flocks with indoor lambing.


Interaction of CD38 Variant and Chronic Interpersonal Stress Prospectively Predicts Social Anxiety and Depression Symptoms Over Six Years.
Variation in the CD38 gene, which regulates secretion of the neuropeptide oxytocin, has been associated with several social phenotypes. Specifically, rs3796863 A allele carriers have demonstrated increased social sensitivity. In 400 older adolescents, we used trait-state-occasion modeling to investigate how rs3796863 genotype, baseline ratings of chronic interpersonal stress, and their gene-environment (GxE) interaction predicted trait social anxiety and depression symptoms over six years. We found significant GxE effects for CD38 A-carrier genotypes and chronic interpersonal stress at baseline predicting greater social anxiety and depression symptoms. A significant GxE effect of smaller magnitude was also found for C/C genotype and chronic interpersonal stress predicting greater depression; however, this effect was small compared to the main effect of chronic interpersonal stress. Thus, in the context of chronic interpersonal stress, heightened social sensitivity associated with the rs3796863 A allele may prospectively predict risk for social anxiety and (to a lesser extent) depression.


Possible association of aldosterone producing adenoma and non-functioning adrenal tumor.
A 37-year-old woman presented with hyperaldosteronism, suppressed renin levels, and a left adrenal mass on CT scanning. Selective adrenal venous sampling indicated a marked rise of the aldosterone level in the right adrenal vein, while the level in the left vein was low. On laparotomy, an aldosterone producing adenoma (APA) of 12x10x5 mm in size was found in the right adrenal gland and was resected, while the left mass was left in situ. The post-operative course showed normalization of both the clinical and biochemical features of primary aldosteronism, with no sign of recurrence or of enlargement of the remaining adrenal mass in 2.5 years of follow up, suggesting the possible coexistence of a "non-functioning" tumor. This case demonstrates the importance of adrenal venous sampling for the localization of APA particularly since the presence of the APA may be masked by a visualized but unrelated adrenal mass.


Prediction of the binding modes between BB-83698 and peptide deformylase from Bacillus stearothermophilus by docking and molecular dynamics simulation.
BB-83698 is a first potent inhibitor of peptide deformylase in this novel class to enter clinical trials. In this study, automated docking, molecular dynamics simulation and binding free energy calculations with the linear interaction energy (LIE) method are first applied to investigate the binding of BB-83698 to the peptide deformylase from Bacillus stearothermophilus. The lowest docking energy structure from each cluster is selected as different representative binding modes. Compared with the experimental data, the results show that the binding of BB-83698 in Mode 1 is the most stable, with a binding free energy of -41.35 kJ/mol. The average structure of the Mode 1 complex suggests that inhibitor interacts with Ile59 and Gly109 by hydrogen bond interaction and with Pro47, Pro57, Ile59 and Leu146 by hydrophobic interaction are essential for the activity of BB-83698. Mode 2 represents a new binding mode. Additionally, if the hydrophilic group is introduced to the benzo-[1,3]-dioxole ring, the binding affinity of BB-83698 to the peptide deformylase from B. stearothermophilus will be greatly improved.


Sterics and solvation winnow accessible conformational space for unfolded proteins.
The magnitude of protein conformational space is over-estimated by the traditional random-coil model, in which local steric restrictions arise exclusively from interactions between adjacent chain neighbors. Using a five-state model, we assessed the extent to which steric hindrance and hydrogen bond satisfaction, energetically significant factors, impose additional conformational restrictions on polypeptide chains, beyond adjacent residues. Steric hindrance is repulsive: the distance of closest approach between any two atoms cannot be less than the sum of their van der Waals radii. Hydrogen bond satisfaction is attractive: polar backbone atoms must form hydrogen bonds, either intramolecularly or to solvent water. To gauge the impact of these two factors on the magnitude of conformational space, we systematically enumerated and classified the disfavored conformations that restrict short polyalanyl backbone chains. Applying such restrictions to longer chains, we derived a scaling law to estimate conformational restriction as a function of chain length. Disfavored conformations predicted by the model were tested against experimentally determined structures in the coil library, a non-helix, non-strand subset of the PDB. These disfavored conformations are usually absent from the coil library, and exceptions can be uniformly rationalized.


[Multiparametric imaging with simultaneous MR/PET. Methodological aspects and possible clinical applications].
Combined magnetic resonance imaging-positron emission tomography (MR/PET) enables acquisition of a variety of imaging parameters during a single examination including anatomical as well as functional information, such as perfusion, diffusion and metabolism. Numerous studies have shown that the combination of these parameters can improve the diagnostic accuracy for many applications especially in oncological imaging. Due to the amount and the complexity of the acquired multiparametric data there is a need for advanced analytical tools, such as methods of parameter selection and data classification. The present article summarizes these methods and their applications in multiparametric imaging via MR/PET.


The unique HCV genotype distribution and the discovery of a novel subtype 6u among IDUs co-infected with HIV-1 in Yunnan, China.
The Yunnan province is the epicenter of HIV-1 epidemics in China and a center for drug trafficking to the other parts of the world. In six prefectures of this province, a total of 132 IDUs were recruited to determine the sero-prevalence of HCV and HIV-1 and the positive rates were 93.94% and 68.18%, respectively (P<0.001). Co-infection with HCV and HIV-1 was found among 89 IDUs, of whom several HCV fragments were amplified and sequenced. Sequences of the HCV 5'NCR-C and NS5B region were determined from 82 IDUs. Phylogenetic analyses showed consistent genotyping among 80 IDUs. Among them HCV genotypes 1a, 1b, 3a, 3b, 6a, 6n, and a tentatively assigned novel 6u subtype were found in 1 (1.25%), 16 (20%), 19 (23.75%), 24 (30%), 4 (5%), 9 (11.25%) and 7 (8.75%) individuals, respectively. In two IDUs, genotyping results were discordant, suggesting mixed HCV infections or recombination. The proportion of patients with HCV 1b tended to decrease from the north to south and from the east to west in this province. Genotype 3 and 6 strains were more frequent in the southern prefectures. The novel subtype 6u strains were only detected in Dehong which borders Myanmar. Our findings showed a unique pattern of HCV genotype distribution, which is similar to that in the southeastern Asian countries but distinct from that among the general population in China. Routes of drug trafficking and the resulting high prevalence of HIV-1 infection may have contributed to this pattern of HCV genotype distribution.


Toxicological effects and ultrastructural changes induced by lanthanum and cerium in ovary and uterus of Wistar rats.
Rare earths have been widely used in a huge number of areas in industry and medicine. Therefore, they exist in the environment and possibly accumulated within the human body. However their effects in the living organism particularly in the female reproductive system are still unclear. In this work, the subcellular behavior of lanthanum and cerium was investigated through the Transmission Electron Microscopy (TEM), in different territories of the reproductive system of Wistar rats exposed intraperitoneally to soluble solution of these elements during 2 weeks. Ultrastructural investigations of ultrathin sections from uterus and ovary of treated rats revealed the existence of inclusions with high electron density and heterogeneous aspects in the lysosomes of uterus and ovary cells. Many disruptions of architecture were observed, accompanied with several changes like vacuolations, significant expansion of the endoplasmic reticulum, mitochondrial alterations and necrotic cells, demonstrating the toxicity of these elements with doses used. Phagolysosomes as well as eosinophils were also seen. Our experimental investigations revealed no intralysosomal inclusions in ultrathin sections of the uterus and ovary of pregnant control females. The original mechanism implicated in this insolubilization-concentration phenomenon of these elements, as non-soluble phosphate form, in the lysosomes is a biochemical one involving intralysosomal hydrolytic enzymes, the acid phosphatase.


T-T cell interactions are mediated by adhesion molecules.
The mechanism by which T cells signal other T cells is not well defined. This was investigated by studying the ability of circulating T cells to induce the proliferation of autologous T cell clones. Peripheral blood T cells activated by cross-linking of the CD3/T cell receptor complex, which increased the expression of cell adhesion molecules LFA-1, LFA-3 and ICAM-1, induced the proliferation of autologous T cell clones. Irradiated antigen-activated peripheral blood T cells could also induce the proliferation of T cell clones which could not recognize that antigen. T-T cell activation required cell contact, was not major histocompatibility complex (MHC) restricted and was blocked by monoclonal antibodies directed against adhesion molecules CD2 and LFA-3 but was not blocked by antibody to class II MHC determinants. As CD2 is the natural ligand for LFA-3, increased expression of T cell surface adhesion molecules LFA-1, ICAM-1 and particularly LFA-3 during an inflammatory response may rapidly recruit T cells that are activated through the CD2 pathway. These results allow a simplified model to explain how relatively few antigen/MHC-specific T cells can recruit large numbers of non-antigen-specific T cells in the generation of an inflammatory response and postulates a novel role of the CD2 molecule in T cell immune function.


MAGI-1 is a component of the glomerular slit diaphragm that is tightly associated with nephrin.
MAGUK with inverted domain structure-1 (MAGI-1) is a membrane-associated protein with one guanylate kinase, six PSD-95/Dlg-A/ZO-1 (PDZ), and two WW domains and is localized at tight junctions in epithelial cells. MAGI-1 interacts with various proteins and is proposed to function as a scaffold protein. In the previous study, we discovered a MAGI-1-interacting cell adhesion molecule junctional adhesion molecule 4 (JAM4). Both proteins are highly expressed in glomerular podocytes in the kidney and partially colocalized. In this study, we have further searched for a binding partner of MAGI-1 in the kidney through yeast two-hybrid screening and obtained nephrin. Nephrin is a cell adhesion molecule specifically localized at the slit diaphragm between neighboring foot processes of podocytes. Biochemical studies reveal that nephrin directly binds to the middle PDZ domains of MAGI-1 through its carboxyl terminus but does not bind to ZO-1. MAGI-1 forms a tripartite complex with nephrin and JAM4 in vitro. Immunoelectron microscopy shows that the localization of MAGI-1 is restricted to the slit diaphragm, whereas JAM4 is also distributed on apical membranes of podocytes. In puromycin aminonucleoside-induced nephrotic podocytes, MAGI-1 is localized with nephrin at the displaced slit diaphragm. These data indicate that MAGI-1 is a component of the slit diaphragm and tightly interacts with nephrin and JAM4 in vivo. MAGI-1 may play a role in determining the boundary between the apical and the bosolateral domain at the level of slit diaphragm.


Patient-centered communication in type 2 diabetes: The facilitating and constraining factors in clinical encounters.
To explore the perceptions of the constraining and facilitating factors to patient-centered communication in clinical encounters of patients with type 2 diabetes and the providers involved in their care. Patients (n = 12) and providers (n = 33) involved in diabetes care in northern Portugal. Seven focus groups. Grounded theory, using open, axial, and selective coding. Patients focused on the patient-provider relationship, while providers emphasized the constraining factors when exchanging information and the facilitating factors regarding disease and treatment-related behavior. Patients and providers both agreed on some constraints (power imbalance, avoidance of criticism, disease minimization, use of jargon, and insufficient competencies and consistency among providers) and facilitators (seeing patients as persons, providing tailored information in plain language, and recognizing the "wake-up call"). Patients perceived an aggressive attitude as a barrier to communication, but providers perceived it as a facilitator. Patients included issues related to trust, respect, and psychosocial support as important factors to them. Only providers mentioned the influence of macro-level interventions and patients' socioeconomic position as essential factors. Improvements in patient-centered communication depend on fostering the patient-provider relationship, patients' participation and involvement, and training providers' communication skills.


Characterization of honeybee venom by MALDI-TOF and nanoESI-QqTOF mass spectrometry.
The aim of the study was to comprehensively characterize different honeybee venom samples applying two complementary mass spectrometry methods. 41 honeybee venom samples of different bee strains, country of origin (Poland, Georgia, and Estonia), year and season of the venom collection were analyzed using MALDI-TOF and nanoESI-QqTOF-MS. It was possible to obtain semi-quantitative data for 12 different components in selected honeybee venom samples using MALDI-TOF method without further sophisticated and time consuming sample pretreatment. Statistical analysis (ANOVA) has shown that there are qualitative and quantitative differences in the composition between honeybee venom samples collected over different years. It has also been demonstrated that MALDI-TOF spectra can be used as a "protein fingerprint" of honeybee venom in order to confirm the identity of the product. NanoESI-QqTOF-MS was applied especially for identification purposes. Using this technique 16 peptide sequences were identified, including melittin (12 different breakdown products and precursors), apamine, mast cell degranulating peptide and secapin. Moreover, the significant achievement of this study is the fact that the new peptide (HTGAVLAGV+Amidated (C-term), M(r)=822.53Da) has been discovered in bee venom for the first time.


[Effect of voltage errors of an x-ray diagnostic apparatus on the quality of the x-ray image].
The technical suitability of key assemblies in the roentgen unit and the quality of X-ray examinations depend upon a proper choice of permissible voltage setting errors in the X-ray tube. To determine the permissible voltage setting errors in the roentgen apparatus a criterion for the required accuracy of such settings has been suggested and the voltage error in Soviet-made units operating in medical establishments assessed experimentally.


Association of interleukin-4 and interleukin-1 receptor antagonist gene polymorphisms and risk of benign prostatic hyperplasia.
The genetic and cellular processes involved in the etiopathology of benign prostatic hyperplasia (BPH) are unknown. Although evidence of BPH as an immune-mediated disease distinct from prostate cancer is growing, the cytokine gene polymorphisms associated with the risk of BPH have been explored less. The purpose of this study was to investigate the genetic association of polymorphisms of important cytokine genes (IL-4 and IL-1Ra) with the risk of BPH in a case-control study of a North Indian population. The IL-4 and IL-1Ra gene polymorphisms were genotyped with variable number of tandem repeats-polymerase chain reaction in 150 patients with BPH and normal healthy controls. On the basis of their response to combined therapy of alpha-adrenergic inhibitor plus 5-alpha-reductase inhibitor, patients were grouped as responders and nonresponders. The genotype distribution and allelic frequencies between the patients and controls were compared, and odds ratios with 95% confidence intervals were calculated using Statistical Package for Social Sciences software, version 11.5. The difference in genotype frequency distribution for the IL-4 and IL-1Ra gene polymorphisms between the BPH and control groups were statistically significant (P <0.05). A significant difference (P <0.05) was also observed between the responder and nonresponder groups in the IL-4 gene variants. IL-4 and IL-1Ra gene polymorphisms are associated with the risk of BPH. This study for the first time has demonstrated an association between the IL-4 polymorphism and BPH and particularly influences the therapeutic response of patients.


Association of spermidine blood levels with microstructure of sleep-implications from a population-based study.
Deteriorations in slow wave sleep (SWS) have been linked to brain aging and Alzheimer's disease (AD), possibly due to its key role in clearance of amyloid-beta and tau (Aß/tau), two pathogenic hallmarks of AD. Spermidine administration has been shown to improve sleep quality in animal models. So far, the association between spermidine levels in humans and parameters of SWS physiology are unknown but may be valuable for therapeutic strategies. Data from 216 participants (age range 50-81 years) of the population-based Study of Health in Pomerania TREND were included in our analysis. We investigated associations between spermidine plasma levels, key parameters of sleep macroarchitecture and microarchitecture that were previously associated with AD pathology, and brain health measured via a marker of structural brain atrophy (AD score). Higher spermidine levels were significantly associated with lower coupling between slow oscillations and spindle activity. No association was evident for SWS, slow oscillatory, and spindle activity throughout non-rapid eye movement sleep. Furthermore, elevated spermidine blood levels were significantly associated with a higher AD score, while sleep markers revealed no association with AD score. The association between higher spermidine levels and brain health was not mediated by coupling between slow oscillations and spindle activity. We report that higher spermidine blood levels are associated not only with deteriorated brain health but also with less advantageous markers of sleep quality in older adults. Future studies need to evaluate whether sleep, spermidine, and Aß/tau deposition are interrelated and whether sleep may play a mediating role.


Improved sulfoalkylbetaine-based organic-silica hybrid monolith for high efficient hydrophilic interaction liquid chromatography of polar compounds.
A novel sulfoalkylbetaine-based zwitterionic organic-silica hybrid monolith was synthesized by using 3-dimethyl-(3-(N-methacrylamido) propyl) ammonium propane sulfonate (DMMPPS, neutral sulfoalkyl-betaine monomer). The added amount of zwitterionic monomer was significantly increased when DMMPPS was used instead of the conventionally used acidic sulfoalkyl-betaine monomer, that is, the N,N-dimethyl-N-methacryloxyethyl-N-(3-sulfopropyl) ammonium betaine, and this led to a significantly improved hydrophilicity of the monolith. The DMMPPS-based organic-silica hybridmonolith exhibited good mechanical stability and excellent separation performance. About ∼20 mμ plate height (corresponding to column efficiency of ∼50,000 plates/m) was obtained for nucleoside at the linear velocity of 1 mm/s. The proposed monolithic column was successfully applied to separate purines/pyrimidines, nucleotides, and tryptic digest of bovine hemoglobin in a nano-HILIC mode, and the results demonstrated that such monolith has the potential for separation of a variety of hydrophilic substances.


Prevalence of concurrent hearing and visual impairment in US adults: The National Health Interview Survey, 1997-2002.
Analysis of data from a nationally representative sample of US adults (n=195801) showed that concurrent hearing and visual impairment prevalence rates were highest for participants older than 79 years of age (16.6%); a 3-fold increase in age-adjusted rates of reported hearing and visual impairment was observed for Native Americans compared with Asian Americans. Research on preventing concurrent hearing and visual impairment and countering its consequences is warranted, especially in population subgroups, such as Native and older Americans.


Lab-scale transport and activation of peroxydisulfate for phenanthrene degradation in soil: A comprehensive assessment of the remediation process, soil environment and microbial diversity.
Electrokinetic transport followed by electrical resistance heating activation of peroxydisulfate is a novel in situ soil remediation method. However, the strategy of electrokinetic transport coupled with electrical resistance heating and the comprehensive evaluation of restored soil need to be further explored. In this study, a lab-scale simulation device for in situ electrokinetic transport coupled with electrical resistance heating activation of peroxydisulfate was constructed to monitor the transport and transfer of peroxydisulfate, target pollutants, and process parameters, and the physicochemical properties and bacterial community of treated soil were evaluated. The results showed that adding 10 wt% peroxydisulfate to both the anode and cathode resulted in the optimized transfer rate and cumulative concentration of peroxydisulfate under electrokinetics. After 8 h, the cumulative concentration of peroxydisulfate reached 66.15- 166.29 mmol L-1, which was attributed to the migration of a large amount of S2O82- from the cathode to the soil under electromigration. Additionally, the anodic interfacial electric potential was improved, which was more conducive to electroosmotic transport of peroxydisulfate from the anode chamber. By alternating electrokinetic transport and electrical resistance heating activation of peroxydisulfate for two cycles, the phenanthrene degradation efficiency in four evenly distributed wells between electrodes reached 75.4 %, 87.6 %, 92.3 %, and 94.4 %. With slight variations in soil morphology and structure, the electrokinetic transport coupled with electrical resistance heating activation of peroxydisulfate elevated the soil fertility index. The abundance and diversity of bacterial communities in treated soil recovered to above the original soil level after 15 days. Our findings may support the application of electrokinetic transport coupled with electrical resistance heating activation of peroxydisulfate as a promising green ecological technology for the in situ remediation of organic-contaminated soil.


High-performance liquid chromatographic determination of cilastatin and its major metabolite N-acetylcilastatin in rat plasma, urine and bile.
A new high-performance liquid chromatographic method coupled with solid-phase (C8) sample extraction has been developed for the simultaneous quantification of cilastatin and its major metabolite N-acetylcilastatin in rat plasma, urine and bile. The method is linear, reproducible and reliable with a detection limit of 1 microgram/ml in all three fluids. Plasma concentrations of cilastatin and N-acetylcilastatin at selected time intervals and biliary and urinary recoveries of cilastatin and N-acetylcilastatin following an intravenous dose of 10 mg/kg cilastatin are presented.


Effect of different resuscitation strategies on neutrophil activation in a swine model of hemorrhagic shock.
Activated neutrophils play a pivotal role in resuscitation injury. The strategies used for resuscitation (types of fluids and methods of administration) can affect the degree of neutrophil activation. The aim of this study was to test the commonly available resuscitation fluids in a large animal model of hemorrhagic shock to determine the strategy associated with the least degree of neutrophil activation. Female swine (n=63, weight 45-60 kg) were anesthetized using isoflurane and catheters were placed for hemodynamic monitoring. After 120 min, they were subjected to a volume controlled hemorrhage (28 ml/kg) over 15 min, kept in shock for 60 min, and then resuscitated. The resuscitation groups were as follows: (1) anesthesia only (n=5); (2) hemorrhage, sham resuscitation (n=5); (3) LR-fast rate 3x blood loss (n=6); (4) LR slow rate-3x blood loss (n=6); (5) LR low volume-1x blood loss (n=6); (6) Dextran 40-1x blood loss (n=6); (7) 6% hetastarch-1x blood loss (n=6); (8) 5% albumin-1x blood loss (n=6); (9) 25% albumin-1/5x blood loss (n=6); (10) whole blood resuscitation-1x blood loss (n=6); (11) 7.5% hypertonic saline (HTS)-0.3x blood loss (n=5). Resuscitation fluids were infused over 1 h in all groups except group 4 (LR slow rate, which was over 3 h). Animals were observed for 180 min following the resuscitation period. Neutrophil oxidative burst activity was determined in whole blood using flow cytometery. Animals resuscitated with dextran and hetastarch showed significantly (P<0.05) higher neutrophil burst activity. Resuscitation with LR also caused neutrophil activation (P<0.05), and the highest degree of activation was seen when a large volume of LR was given at a fast rate (group 8). However, all LR infusion protocols were associated with significant neutrophil activation compared with anesthesia (group 1) or sham resuscitation (group 2). No significant activation was seen in the animals resuscitated with albumin or fresh whole blood. Artificial colloids and LR (independent of rate or volume of infusion) caused significant neutrophil activation, which was not seen with albumin and whole blood resuscitation. These findings suggest that the type of resuscitation fluid and method of infusion can influence neutrophil function.


Antagonistic effects of caffeine and alcohol on mental performance parameters.
Scientific experiments done so far allow no clear conclusions about the popular belief that freshly brewed coffee can offset the debilitating effects of alcoholic intoxication. This question was addressed using a computer-controlled and subject-paced rapid information processing task (RIP) which was shown earlier to be sensitive to psychoactive substances. Nine male students were tested in a Latin square design before and after the intake of 3.3 mg/kg caffeine (or placebo) followed by 0.7 g/kg alcohol (or placebo). Whereas the mean RIP-task processing rate and the mean reaction time were impaired by alcohol and improved by caffeine, no changes were observed after the combination of alcohol and caffeine. Thus, it was concluded that under the tested conditions, caffeine was able to offset the debilitating effects of alcohol.


[Most frequent drug-related events detected by pharmacists during prescription analysis in a university hospital].
In France, the analysis of the prescriptions by a pharmacist in hospital is mandatory since 1991. However, for various reasons, this activity remained poorly developed and little research has been performed. Consequently, this activity suffers of a lack of visibility to hospital decision-makers and others health care professionals. The aim of this paper is to describe drugs related problems identified by pharmacist prescriptions analysis on a large number of orders in a large teaching hospital. This was done in order to highlight recurrent and preventable problems. During 1 year period, drug related problems detected by pharmacists when performing prescription analysis were registered prospectively. Among 70,849 orders, 7073 drug related problems were registered. Most frequently detected drug related problems were: over dosages, especially with three drugs (zopiclone, zolpidem and acetaminophen) representing more than 10% of the pharmacist's interventions; optimization of drug administration especially with tablets that should not be crushed and intravenous to oral step-down therapy (7.5%); lack of conformity with consensus recommendations and contra-indications (12.8%); drug-drug interactions (11.6%) with a high proportion of absorption inhibition of one drug by another along the digestive tract; problems related to computerized physicians order entry (5.1%) appeared as an emerging phenomenon. These results should be used to reexamine hospital drug prescription policy. They prompt health care professionals to be aware about new medications errors potentially related to computerized prescription order entry. Finally, they invite to modify initial and continuous education programs of health care professionals.


Identification of high and low (GTP-sensitive) affinity [3H]glibenclamide binding sites in cardiac ventricular membranes.
Glibenclamide is an antagonist of the ATP-modulated K+ channel in cardiac tissue. This study showed glibenclamide to bind to high (0.2 nM) and low (40 nM) affinity binding sites in canine ventricular membranes. Gpp [NH]p significantly altered the binding characteristics of the low affinity site, while those of the high affinity site were unchanged. This indicates independence of the two sites and suggests the low affinity site may be coupled to a G-binding protein. Although we have identified two [3H]glibenclamide binding sites, the importance of these sites to the cardiac effects of glibenclamide remains to be determined.


Mechanically facilitated micro-fluid mixing in the organ of Corti.
The cochlea is filled with two lymphatic fluids. Homeostasis of the cochlear fluids is essential for healthy hearing. The sensory epithelium called the organ of Corti separates the two fluids. Corti fluid space, extracellular fluid space within the organ of Corti, looks like a slender micro-tube. Substantial potassium ions are constantly released into the Corti fluid by sensory receptor cells. Excess potassium ions in the Corti fluid are resorbed by supporting cells to maintain fluid homeostasis. Through computational simulations, we investigated fluid mixing within the Corti fluid space. Two assumptions were made: first, there exists a longitudinal gradient of potassium ion concentration; second, outer hair cell motility causes organ of Corti deformations that alter the cross-sectional area of the Corti fluid space. We hypothesized that mechanical agitations can accelerate longitudinal mixing of Corti fluid. Corti fluid motion was determined by solving the Navier-Stokes equations incorporating nonlinear advection term. Advection-diffusion equation determined the mixing dynamics. Simulating traveling boundary waves, we found that advection and diffusion caused comparable mixing when the wave amplitude and speed were 25 nm and 7 m/s, respectively. Higher-amplitude and faster waves caused stronger advection. When physiological traveling waves corresponding to 70 dB sound pressure level at 9 kHz were simulated, advection speed was as large as 1 mm/s in the region basal to the peak responding location. Such physiological agitation accelerated longitudinal mixing by more than an order of magnitude, compared to pure diffusion. Our results suggest that fluid motion due to outer hair cell motility can help maintain longitudinal homeostasis of the Corti fluid.


Orolaelaps (Acari: Mesostigmata: Melicharidae): description of two new species, redescription of Orolaelaps quisqualis and new characterisation of the genus.
Until now, the genus Orolaelaps De Leon was known only from the USA. Two new species of this genus, namely Orolaelaps piracicabensis n. sp. and Orolaelaps tupiniquim n. sp., are described from specimens collected in the State of São Paulo, Brazil. Orolaelaps quisqualis De Leon, the type species of the genus, is redescribed and an updated diagnosis of Orolaelaps is provided.


Eye lens-derived Δ14C signatures validate extreme longevity in the deepwater scorpaenid blackbelly rosefish (Helicolenus dactylopterus).
Many members of the scorpaenid subfamily: Sebastinae (rockfishes and their relatives) exhibit slow growth and extreme longevity (> 100 y), thus are estimated to be vulnerable to overfishing. Blackbelly rosefish (Helicolenus dactylopterus) is a deepwater sebastine whose longevity estimates range widely, possibly owing to different regional levels of fisheries exploitation across its Atlantic Ocean range. However, age estimation has not been validated for this species and ageing for sebastines in general is uncertain. We performed age validation of northern Gulf of Mexico blackbelly rosefish via an application of the bomb radiocarbon chronometer which utilized eye lens cores instead of more traditional otolith cores as the source of birth year Δ14C signatures. The correspondence of eye lens core Δ14C with a regional reference series was tested with a novel Bayesian spline analysis, which revealed otolith opaque zone counts provide accurate age estimates. Maximum observed longevity was 90 y, with 17.5% of individuals aged to be > 50 y. Bayesian growth analysis, with estimated length-at-birth included as a prior, revealed blackbelly rosefish exhibit extremely slow growth (k = 0.08 y-1). Study results have important implications for the management of blackbelly rosefish stocks, as extreme longevity and slow growth imply low resilience to fishing pressure.


The gene cluster inlC2DE of Listeria monocytogenes contains additional new internalin genes and is important for virulence in mice.
In this work we identified and characterized a gene cluster containing three internalin genes of Listeria monocytogenes EGD. These genes, termed inlG, inlH and inlE, encode proteins of 490, 548 and 499 amino acids, respectively, which belong to the family of large, cell wall-bound internalins. The inlGHE gene cluster is flanked by two listerial house-keeping genes encoding proteins homologous to the 6-phospho-beta-glucosidase and the succinyl-diaminopimelate desuccinylase of E. coli. A similar internalin gene cluster, inlC2DE, localised to the same position on the L. monocytogenes EGD chromosome was recently described in a different isolate (Dramsi S, Dehoux P, Lebrun M, Goossens PL, Cossart P (1997) Infect Immun 65: 1615-1625). Sequence comparison of the two inl gene clusters indicates that inlG is a new internalin gene, while inlH was generated by a site-specific recombination, leading to an in-frame deletion which removed the 3'-terminal end of inlC2 and the 5'-terminal part of inlD. The third gene of the inlGHE cluster, inlE, is almost identical to the previously reported inlE gene. Our data show that the inlGHE gene cluster is probably transcribed from a major PrfA-independent promoter located upstream of inlG. PCR analysis revealed the presence of the newly identified inl genes inlG and inlH in most L. monocytogenes isolates tested. A mutant which has lost inlG, inlH and inlE by an in-frame deletion exhibited, after oral infection of mice, a significant loss in virulence and shows drastically reduced numbers of viable bacteria in both liver and spleen when compared to the wild-type strain.


Hepatitis B virus and other transfusion-transmissible infections in child blood recipients in Lao People's Democratic Republic: a hospital-based study.
Children requiring multiple blood transfusions are at high risk of transfusion-transmissible infections (TTIs). Lao People's Democratic Republic is a low-resource setting where donor blood screening faces challenges. This study aimed to determine the burden of TTIs in children in Vientiane Capital. 300 children with transfusion history and 300 controls were recruited. In addition, 49 newly diagnosed transfusion recipients were followed for up to 12 months. Serum was tested for hepatitis B surface antigen and IgG antibodies against parvovirus B19, hepatitis B, C and E viruses. The patients had a similar prevalence of anti-hepatitis B core antibodies (56; 18.7%) and hepatitis B surface antigen (8; 2.7%) as the controls (58; 19.3% and 9; 3.0%, respectively). However, there was a higher prevalence of an antibody profile suggestive of hepatitis B vaccination (anti-hepatitis B surface antibody positive/anti-hepatitis B core antibody negative) in the transfused group (140/299; 46.8%) than in controls (77/300; 25.7%, p<0.01). All other markers were similar in the patients and controls or higher in the controls: anti-hepatitis C virus (2.7% and 3.3%, p=0.6), anti-hepatitis E virus (7.5% and 12.7%, p=0.006) and anti-parvovirus B19 (2.4% and 8.5%, p=0.001). The longitudinal cohort did not show an increase in any marker over time. Our results suggest no significant role of TTIs in Lao children. The higher prevalence of the hepatitis B vaccination profile in transfusion recipients showed that recommendations to vaccinate before commencing transfusions is at least partially implemented, although there is room for improvement.


Toward a Realistic Model of Diffusion-Limited Aggregation: Rotation, Size-Dependent Diffusivities, and Settling.
In this Brownian dynamics simulation study on the formation of aggregates made of spherical particles, we build on the well-established diffusion-limited cluster aggregation (DLCA) model. We include rotational effects, allow diffusivities to be size-dependent as is physically relevant, and incorporate settling under gravity. We numerically characterize the growth dynamics of aggregates and find that their radius of gyration, R g, grows approximately as R g ∼ t 1.02 for classical DLCA but slows to an approximate growth rate of R g ∼ t 0.71 when diffusivity is size-dependent. We also analyze the fractal structure of the resulting aggregates and find that their fractal dimension, d, decreases from d ≈ 1.8 for classical DLCA to d ≈ 1.7 when size-dependent rotational diffusion is included. The addition of settling effects further reduces the fractal dimension observed to d ≈ 1.6 and appears to result in aggregates with a vertical extent marginally smaller than their horizontal extent.


Susceptibility of N-acetyltransferase 2 slow acetylators to antituberculosis drug-induced liver injury: a meta-analysis.
This study aimed to evaluate the association between N-acetyltransferase 2 (NAT2) gene polymorphisms and the risk of antituberculosis drug-induced liver injury (ATLI). A meta-analysis was performed including 27 studies with 1289 cases and 5462 controls. Odds ratio with 95% CI was used to evaluate the strength of association. Our meta-analysis found that NAT2 slow acetylators were associated with increased risk of ATLI compared with fast and intermediate acetylators when standard dose of isoniazid was administrated (odds ratio: 3.08; 95% CI: 2.29-4.15). Individuals with NAT2 slow acetylators may have increased risk of ATLI when standard dose of isoniazid was used. Detection of NAT2 genotype may benefit to the prevention of ATLI.


Optimal time point of response assessment for predicting survival is associated with tumor burden in hepatocellular carcinoma receiving repeated transarterial chemoembolization.
Objective response rate (ORR) under mRECIST criteria after transarterial chemoembolization (TACE) is a well-perceived surrogate endpoint of overall survival (OS). However, its optimal time point remains controversial and may be influenced by tumor burden. We aim to investigate the surrogacy of initial/best ORR in relation to tumor burden. A total of 1549 eligible treatment-naïve patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh score ≤ 7, and performance status score ≤ 1 undergoing TACE between January 2010 and May 2016 from 17 academic hospitals were retrospectively analyzed. Based on "six-and-twelve" criteria, tumor burden was graded as low, intermediate, and high if the sum of the maximum tumor diameter and tumor number was ≤ 6, > 6 but ≤ 12, and > 12, respectively. Both initial and best ORRs interacted with tumor burden. Initial and best ORRs could equivalently predict and correlate with OS in low (adjusted HR, 2.55 and 2.95, respectively, both p < 0.001; R = 0.84, p = 0.035, and R = 0.97, p = 0.002, respectively) and intermediate strata (adjusted HR, 1.81 and 2.22, respectively, both p < 0.001; R = 0.74, p = 0.023, and R = 0.9, p = 0.002, respectively). For high strata, only best ORR exhibited qualified surrogacy (adjusted HR, 2.61, p < 0.001; R = 0.70, p = 0.035), whereas initial ORR was not significant (adjusted HR, 1.08, p = 0.357; R = 0.22, p = 0.54). ORR as surrogacy of OS is associated with tumor burden. For patients with low/intermediate tumor burden, initial ORR should be preferred in its early availability upon similar sensitivity, whereas for patients with high tumor burden, best ORR has optimal sensitivity. Timing of OR assessment should be tailored according to tumor burden. • This is the first study utilizing individual patient data to comprehensively analyze the surrogacy of ORR with a long follow-up period. • Optimal timing of ORR assessment for predicting survival should be tailored according to tumor burden. • For patients with low and intermediate tumor burden, initial ORR is optimal for its timeliness upon similar sensitivity with best ORR. For patients with high tumor burden, best ORR has optimal sensitivity.


Phalloidin inhibits cortical granule exocytosis and ooplasmic segregation in loach eggs.
Injections of phalloidin under the surface of loach eggs, followed by activation of the eggs in tap water, result in local inhibition of cortical granule (CG) exocytosis. Light and electron microscopy revealed that in the region where exocytosis is inhibited the thickness of the microfilamentous cortex (MC) separating CGs from the plasma membrane (PM) is increased significantly, and many CGs are detached and have moved away from the MC. Injections of phalloidin also inhibit ooplasmic segregation in fertilized eggs. The experiments suggest that in intact eggs the MC represents a physical barrier to CG exocytosis, and that interactions of the MC with the PM and CGs are crucial for the retention of CGs near the sites of fusion.


Leech locomotion: swimming, crawling, and decisions.
Research on the neuronal control of locomotion in leeches spans almost four decades. Recent advances reviewed here include discoveries that: (1) interactions between multiple hormones modulate initiation of swimming; (2) stretch receptors associated with longitudinal muscles interact with the central oscillator circuit via electrical junctions; (3) intersegmental interactions, according to theoretical analyses, must be relatively weak compared to oscillator interactions within ganglia; and (4) multiple interacting neurons control the expression of alternative modes of locomotion. The innovative techniques that facilitated these advances include optical recording of membrane potential changes, simultaneous intracellular injection of high and low molecular weight fluorescent dyes, and detailed modeling via an input-output systems engineering approach.


Correlation between cocoa shell modifications by CTAB and its dye adsorption properties.
Cocoa shell was modified whit sodium hydroxide (NaOH) and cationic surfactant cetyltrimethylammonium bromide (CTAB) to increase surface functionality, surface area, and positive charge density. The prepared adsorbent CC-OH-CTAB was used to remove indigo carmine (IC) and bromocresol green (BCG) dyes from water. The optimal pH for IC and BCG adsorption were 2 and 4, respectively. The equilibrium was attained after a contact time of 30 min for IC and 120 min for BCG. The maximum adsorption capacity (Qmax) of IC and BCG obtained was 85.1 mg g-1 and 192.7 mg g-1, respectively. The Liu isotherm model best described the equilibrium results. The adsorption kinetics model showed that IC and BCG adsorption onto CC-OH-CTAB followed the pseudo-first-order and pseudo-second-order model, respectively. The regeneration and reusability experiments indicated that CC-OH-CTAB had much stability and excellent performance meanwhile repeatedly used. Finally, the insertion of CTAB on the CC-OH surface proved to be an excellent way to improve the adsorption performance of this material concerning dyes.


Comparative efficacy of chloroquine plus chlorpheniramine and halofantrine in acute uncomplicated falciparum malaria in Nigerian children.
In the face of growing chloroquine resistance of Plasmodium falciparum, efforts to prolong the clinical usefulness of the drug have partly concentrated on its combination with potential resistance-reversing compounds. However, clinical studies on such combinations have been limited. We have compared the efficacy of halofantrine, an arylaminoalcohol effective in chloroquine resistant malaria, and a combination of chloroquine plus chlorpheniramine, a histamine H1 receptor antagonist which reverses chloroquine resistance of P. falciparum in vitro and in vivo, in 100 children with acute symptomatic uncomplicated falciparum malaria in an area in Nigeria where the rate of chloroquine resistance is 35-45%. Both chloroquine plus chlorpheniramine and halofantrine produced similar parasite and fever clearance times and cure rates (96%). Both treatment regimens were relatively well tolerated. Pruritus was commoner in patients treated with chloroquine plus chlorpheniramine than in those treated with halofantrine. Intravascular haemolysis occurred in one patient, and abdominal pain with or without diarrhoea occurred in 4 patients, treated with halofantrine. In vitro, the chloroquine resistance of P. falciparum isolates obtained from the patients was reversed by verapamil. All patients with isolates which were chloroquine-resistant in vitro were cured by either therapy. These results indicate that chloroquine plus chlorpheniramine is as effective as halofantrine and is without overt deleterious effect in treating acute uncomplicated chloroquine-resistant falciparum malaria in children, and may be a clinically useful alternative for this purpose in Nigeria.


Improved Agrobacterium rhizogenes-mediated hairy root culture system of Withania somnifera (L.) Dunal using sonication and heat treatment.
An improved Agrobacterium rhizogenes-mediated genetic transformation of Withania somnifera (L.) Dunal was developed using the bacterial strain R1000 with leaf segment explants of in vitro raised plantlets. Out of the three strains used (R1000, MTCC 2364 and MTCC 532), the strain R1000 proved to be more efficient than others. Among the different conditions tested, the highest (93.3 %) transformation rate was observed after 3 weeks when the explants were subjected to sonication (15 s) and heat treatment (41 °C for 5 min). Transgenic status of the hairy roots was confirmed by PCR using rol B-specific primers. HPLC analysis showed the ability of hairy roots to synthesize withaferin A and withanolide A, both steroidal lactones of medicinal value. This protocol offers new avenue in A. rhizogenes-mediated hairy root induction and is useful for large-scale production of these bioactive compounds from W. somnifera.


Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule.
Carcinoembryonic antigen (CEA) is a member of a family of cell surface glycoproteins that are produced in excess in essentially all human colon carcinomas and in a high proportion of carcinomas at many other sites. The function of this widely used tumor marker and its relevance to malignant transformation is therefore of considerable interest. We demonstrate here that CEA mediates Ca2+-independent, homotypic aggregation of cultured human colon adenocarcinoma cells (LS-180) and rodent cells transfected with functional CEA cDNA. Furthermore, CEA can effect the homotypic sorting of cells in heterogeneous populations of aggregating cells. CEA can thus be considered a new addition to the family of intercellular adhesion molecules. We also show that, whereas CEA is localized mainly to epithelial cell membranes facing the lumen in normal adult intestine, it is found on adjacent cell membranes in both embryonic intestine and colonic tumors. A model for the role of CEA in the tissue architecture of adult, embryonic, and aberrant tumor intestinal epithelium is presented.


Pro-inflammatory chemokines CCL2, chemerin, IP-10 and RANTES in human serum during an oral lipid tolerance test.
There is a strong coincidence of obesity and a chronic state of modest inflammation. Secretion of pro-inflammatory cytokines from adipocytes and immune cells represents a key mechanism in this process and is affected by fatty acids. A study cohort of 100 overnight fasted healthy volunteers underwent an oral lipid tolerance test (OLTT) by ingestion of 160ml of a protein- and sugar-free lipid emulsion of defined composition. Venal blood was drawn at 0h (fasting) and at 2, 4, and 6h after lipid ingestion. Subjects were characterized by anthropometric and standard laboratory parameters. Serum concentrations of CCL2, IP-10, chemerin, and RANTES were measured by enzyme-linked immunosorbent assay (ELISA). Murine 3T3-L1 adipocytes were stimulated with free fatty acids (FA) and with sex steroids and concentrations of CCL2 and chemerin in cell culture supernatants were measured by ELISA. A significant reduction of circulating CCL2, IP-10, and chemerin concentrations was observed as a consequence of triglyceride ingestion whereas RANTES levels were increased. CCL2 serum concentrations were positively correlated with resistin and visfatin levels and with LDL/HDL ratio and negatively with adiponectin. There were significant differences in chemerin and RANTES serum concentrations in female and male subjects. CCL2 secretion from 3T3-L1 adipocytes was inhibited by treatment with linoleic (LA) and oleic acid (OA) whereas chemerin secretion was induced. Chemerin release from 3T3-L1 adipocytes was inhibited by testosterone. Oral lipid loading is linked to reduced circulating pro-inflammatory chemokines CCL2, IP-10, and chemerin and to increased RANTES levels, suggesting that dietary lipids affect immune function.


Informed consent and the use of placebo in Poland: ethical and legal aspects.
The concept of informed consent was one of the most fruitful ideas that deeply changed the relationships between physicians and their patients from paternalism to respect for the personal autonomy of subjects needing professional medical care. The great progress in medicine, also involving the pharmaceutical industry, has created an increasing need to perform different clinical and experimental trials. The evolution of clinical research in the last decades has influenced strongly the design of these studies. One of the most important changes in this field has been the use of placebo groups in double-blind controlled studies. The controversies have involved not only the use of placebo when standard or proven treatment was available, but also some specific problems concerning the procedure of obtaining informed consent in such trials. This paper briefly presents the evolution of informed consent in Poland as well as different ethical and legal problems concerning informed consent and the use of placebo controls in clinical trials.