Distribution of calmodulin and calmodulin-binding proteins in bovine pituitary: association of myosin light chain kinase with pituitary secretory granule membranes.
Calcium is necessary for secretion of pituitary hormones. Many of the biological effects of Ca2+ are mediated by the Ca2+-binding protein calmodulin (CaM), which interacts specifically with proteins regulated by the Ca2+-CaM complex. One of these proteins is myosin light chain kinase (MLCK), a Ca2+-calmodulin dependent enzyme that phosphorylates the regulatory light chains of myosin, and has been implicated in motile processes in both muscle and non-muscle tissues. We determined the content and distribution of CaM and CaM-binding proteins in bovine pituitary homogenates, and subcellular fractions including secretory granules and secretory granule membranes. CaM measured by radioimmunoassay was found in each fraction; although approximately one-half was in the cytosolic fraction, CaM was also associated with the plasma membrane and secretory granule fractions. CaM-binding proteins were identified by an 125I-CaM gel overlay technique and quantitated by densitometric analysis of the autoradiograms. Pituitary homogenates contained nine major CaM-binding proteins of 146, 131, 90, 64, 58, 56, 52, 31 and 22 kilodaltons (kDa). Binding to all the bands was specific, Ca2+-sensitive, and displaceable with excess unlabeled CaM. Severe heat treatment (100 degrees C, 15 min), which results in a 75% reduction in phosphodiesterase activation by CaM, markedly decreased 125I-CaM binding to all protein bands. Secretory granule membranes showed enhancement for CaM-binding proteins with molecular weights of 184, 146, 131, 90, and 52,000. A specific, affinity purified antibody to chicken gizzard MLCK bound to the 146 kDa band in homogenates, centrifugal subcellular fractions, and secretory granule membrane. No such binding was associated with the granule contents. The enrichment of MLCK and other CaM-binding proteins in pituitary secretory granule membranes suggest a possible role for CaM and/or CaM-binding proteins in granule membrane function and possibly exocytosis.


Long-term socioprofessional and psychological status in workers investigated for occupational asthma in quebec.
To compare the long-term status of workers with occupational asthma (OA) with those of subjects with work-exacerbated asthma (WEA) and nonasthmatic (NA) workers. We contacted 179 subjects investigated for suspected OA at Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada, from 1997 to 2007. Participants completed questionnaires on psychological and functional status, followed by a telephone interview about socioprofessional outcomes and health care utilization. The OA workers are more likely to have been removed from the workplace than the WEA workers. The health-related quality of life of all workers was still impaired. A high prevalence of psychiatric disorders was found among OA and WEA workers. Compared with WEA and OA workers, the NA group showed a higher rate of physician consultations for all causes. Regardless of the diagnosis they received, these workers need to benefit from psychosocial support in the period after investigation for suspicion of OA.


Effects of physical training on bone mineral density in fertile women with idiopathic osteoporosis.
The aim of this study was to investigate whether moderate physical training can improve the bone mineral density (BMD) in women with idiopathic osteoporosis. Ten pre-menopausal women aged 24-44 years diagnosed with idiopathic osteoporosis were included in the study. The physical training program consisted of three fast 30-min walks plus one or two sessions of 1-h training per week during 1 year at a training centre separate from the hospital. All patients were given supplements of vitamin D and calcium. Bone mineral density was measured in the femoral neck area and the lumbar spine by dual energy X-ray absorptiometry. The measurements were performed at baseline and after 12 months of training and compared with the measurements at the time of diagnosis, 1-3 years before the study. Eight women fulfilled the 12-month training period, and their mean (SD) BMD at start was 0.88 (0.08) g/cm(2) in the spine and 0.76 (0.13) g/cm(2) in the femoral neck. The mean spine BMD increase was 0.031 g/cm(2) (3.5%) after 1 year of training, which was significant (Wilcoxon's non-parametric test, p = 0.018). The mean increment in BMD in the femoral neck was insignificant, 0.007 g/cm(2) (0.9%) after the intervention (p = 0.74). However, the bone loss during the 1- to 3-year period from diagnosis to study start was, on average, 0.045 g/cm(2) or 5.0% in the femoral neck (p = 0.042), thus indicating a positive indirect effect of the intervention. There is no evidence-based therapy for women with idiopathic osteoporosis. It is therefore of importance to elucidate the impact of moderate physical activity in this group of patients. A 1-year training program was sufficient to induce a small but significant change in the spine BMD.


Comparing major joint injuries, interventions and late sequelae in elite male handball players with an age-matched control group.
Handball is a contact sport which involves throwing and jumping, exposing players to serious physical stress. There is a high risk of injuries leading to possible long-term sequelae. The aim of this study was to assess the incidence of musculoskeletal injuries in elite male handball players compared with an age-matched control group. Former elite handball players, who had played on the Swiss national team between 1980 and 1985, answered a questionnaire about injuries, surgical interventions and their current health status. A total of 34 athletes were compared with 58 age-matched volunteers, who only engaged in recreational sports or no sports at all. The mean age of the athletes was 58.4 years (range 52-68 years) and did not differ significantly from the mean age of the control group of 58.7 years (range 53-69 years). In the control group, 70 % engaged in recreational sports. There was no statistical difference regarding the life-long incidence of shoulder injuries and surgical interventions, sequelae or persistent shoulder pain. Athletes had more interventions after elbow injuries (0.09 vs. 0, p = 0.047), but the difference with respect to chronic pain or late sequelae was not statistically significant. For knee injuries, there were no significant differences regarding the incidence of injuries or interventions, the prevalence of secondary consequences or persistent pain. Concerning the foot and ankle, there was a significantly higher incidence of injuries (0.5 vs. 0.03, p < 0.001) and interventions (0.5 vs. 0.09, p < 0.001) in athletes, but no statistical difference regarding sequelae or persistent pain. Overall quality of life had identical ratings in both groups (athletes mean 85.9 %, controls mean 85.8 %). Top handball players did not sustain more shoulder or knee injuries than the age-matched control group. The elbow was more at risk in these top athletes, but long-term consequences appeared to be less severe. The most distinctive difference was seen in foot and ankle injuries. A career as an elite handball player had no adverse effect on the overall quality of life of elite handball players 25 to 30 years after retiring from professional sports.


[The antibacterial efficacy of KaVo KEY laser on Enterococcus faecalis within infected root canals and roots surface in vitro].
To evaluate the antibacterial efficacy of KaVo KEY laser on Enterococcus faecalis (E. faecalis) within infected root canals and roots surface in vitro. Fifty single-rooted teeth were selected, and infected root canals and roots surface vitro models were prepared. Then, these specimens were divided into three groups. First group were untreated as blank control. The other two groups were the laser groups: Irradiated 15 s and 30 s respectively with 80 mJ and 140 mJ in root canals and on roots surface. Microbiological samples were collected from root canals and roots surface at two time points (before irrigation and immediately after irrigation). The dentin chips from three different zone of part of root canals in each group were immediately collected and were cultured for 24 h in brain heart infusion (BHI). The number of E. faecalis in root canal and root surface in each of the groups were effectively reduced (P < 0.05), and there was no significant difference between each two groups (P > 0.05). Compared with the blank control, the bacterial number in 100 microm of dental tubules decreased after specimens treated with 80 mJ, and the experimental group irradiated 15 s was a significant decease (P < 0.05). The other groups were no changed in different zone of dental tubules. KaVo KEY laser is effective on sterilizing infected root canals and roots surface. It has also significant effect on bacterial in superficial dental tubules with low energy and short time.


Priming of influenza mRNA transcription is inhibited in CHO cells treated with the methylation inhibitor, neplanocin A.
Chinese hamster ovary cells were pretreated with Neplanocin A, a potent inhibitor of RNA methylation. Analysis of polyadenylated RNA from treated cells by high-pressure liquid chromatography revealed marked decreases of 2'-O-methylation within mRNA cap structures and of internal N6-methyladenosine residues. In these Neplanocin A-treated cells, influenza viral mRNA accumulation was virtually abolished. Cellular RNA from Neplanocin A-treated cells was substantially less efficient than RNA from control cells in priming cell-free influenza transcription reactions. These results suggest that the observed inhibition of influenza virus replication is due at least in part to impaired recognition of undermethylated cellular mRNA cap structures by the influenza polymerase complex.


The consequences of outgroup helping: Children's and adolescents' reasoning.
The goal of this study was to examine the consequences of helping an outgroup in an intergroup context where the threat to the ingroup and outgroup varied. Fourth and eighth graders (N = 126; fourth graders: Mage = 9.07 years, SD = 0.38; eighth graders: Mage = 12.84 years, SD = 0.34) were asked whether excluding an ingroup member who helped an outgroup by sharing equally or not was acceptable. Equal helping or outgroup helping occurred when the groups had equal need for a vital resource, the outgroup needed it more, or the ingroup needed it more. Overall, excluding the helpful ingroup member was viewed as unacceptable. It was least acceptable when the outgroup needed the help and was given more help than the ingroup. Exclusion was judged to be most acceptable when both groups needed the same amount of help, or the ingroup needed more help, but more help was given to the outgroup, and these findings were driven by fourth graders. Participants' social cognitions regarding perceptions of group interest, group identification, and approval of the helping act predicted their acceptability of excluding the helping member. Concerns for group loyalty were used to justify exclusion, but appeals to the emotional harm of exclusion, generosity, and the low salience of the act of helping were used to reject exclusion. The findings contribute to developmental research on intergroup relations and exclusion from peer groups.


Current saturation in free-air ionization chambers with chopped synchrotron radiation.
Saturation curves for free-air ionization chambers with electrode gap widths of 4.2, 8.4 and 18 mm were obtained for 10 and 15 keV undulator synchrotron radiation thinned with a 230 Hz rotating-disk chopper. Ion recombination in free-air ionization chambers was found to be inversely proportional to the applied electric field, and an expression that satisfactorily reproduced the ion-recombination rate is determined. A comparison of the expressions for continuous and pulsed X-rays revealed that chopped high-intensity X-rays require a higher voltage to attain saturation when the product of the pulse width and electric field exceeds a value that depends on the X-ray energy. This behaviour was observed explicitly for 10 keV X-rays in measurements with the ionization chamber placed before and after the chopper.


Increased in vitro replication of CC chemokine receptor 5-restricted human immunodeficiency virus type 1 primary isolates in Th2 lymphocytes may correlate with AIDS progression.
It has been found that infection of target cells with the CC chemokine receptor 5-restricted (R5) human immunodeficiency virus type 1 (HIV-1) isolate requires the presence of CD4 and CCR5 molecules on the surface of target cells. We observed that R5 HIV-1 primary isolates from long term survivors replicate less efficiently than the same variants from AIDS progressors in Th1 and Th2 lymphocytes. Real-time quantitative polymerase chain reaction (RQ-PCR) of reverse transcribed messenger RNA, revealed approximately 2 times higher level of CCR5 transcript in Th1 than Th2 cells. Nevertheless we found that R5 HIV-1 primary isolates from long-term survivors and AIDS progressors replicated more efficiently in Th2 than Th1 lymphocytes. These findings correlated with lower-level biosynthesis of regulated upon activation, normal T-cell expressed and secreted (RANTES), and macrophage inflammatory protein-1alpha and -1beta (MIP-1alpha, MIP-1beta), in Th2 than Th1 lymphocytes. Our data indicates that Th0/Th2 cell orientation in HIV-infected individuals and a higher replication of R5 HIV-1 primary isolates in AIDS progressors than long term-survivors can be associated with progression to AIDS.


[Anti-inflammatory and immunosuppressive properties of corticosteroids].
Glucocorticoids exhibit anti-inflammatory, anti-allergic and immunosuppressive properties, which contribute to their beneficial therapeutic effects. The biological effects of their interaction with their soluble receptor have been investigated as well as their inhibitory effects on several proteins implicated in the inflammatory process and on the tissular steps of inflammation. In addition, glucocorticoids exert multiple inhibitory effects both on immunocompetent cells (mainly T-lymphocytes) and on cytokines. Their role on Th17 lymphocytes and regulatory T cells has been recently studied and could represent new mechanisms of action of these drugs.


Synthesis and anticancer activity of new coumarin-3-carboxylic acid derivatives as potential lactatetransportinhibitors.
As an oncometabolite, lactate plays a very important role in tumor proliferation, metastasis, angiogenesis, immune escape and other tumor biological functions. Pharmacological inhibition oflactate transport has been viewed as a promising therapeutic strategy to target a range of human cancers. In this study, a series of new coumarin-3-carboxylic acid derivatives 5a-t and 9a-b were synthesized and evaluated as lactate transport inhibitors. Their cytotoxic activity has been tested against three cell lines high-expressing and low-expressing monocarboxylate transporter 1 (MCT1) which acts as the main carrier for lactate. Compound 5c-e, 5g-i and 5m-o showed significant cytotoxicity and good selectivity against Hela and HCT116 cell lines with high MCT1 expression. Notably, coumarin-3-hydrazide 5o, the lead molecule with the most potent cytotoxic activity, exhibitedsignificant anti-proliferationandapoptosisinductioneffects. Further studies revealed that compound 5o decreased the expression level of target MCT1, and suppressed the energetic metabolism of Hela and HCT116 cells byremarkably reducing glucoseconsumptionandlactate production. Additionally, compound 5o induced intracellular lactate accumulation and inhibited lactate uptake, which implied that it blocked lactate transport via MCT1. These results indicate a good start point for the development of lactate transport inhibitors as new anticancer agents.


Display organization and the detection of horizontal line segments.
Observers searched for a horizontal line segment through displays containing varying numbers of elements differing from the target and from each other in terms of orientation. These elements were always positioned on imaginary concentric circles centered in the middle of the display. They were allocated to these positions either randomly or in such a way that their orientation was equal to that of the tangent to the circle at that position. The search for the target line appeared to proceed spatially in parallel with the latter class of displays, and serially with the former. These findings are explained and discussed within the context of the attentive-preattentive dichotomy that characterizes spatial vision.


How useful are cervical Pap smears in detecting endometrial carcinomas? A tertiary cancer center experience.
To determine the role of routine cervical Pap smears in detecting endometrial carcinomas. A retrospective study was carried out from the histopathology archives for cases diagnosed as endometrial carcinomas with Pap smears within 6 months before histological diagnosis. The demographic details, reports of Pap smears and other tumor parameters on histopathology were noted. We identified 380 of 482 cases of endometrial carcinoma with a documented Pap smear within 6 months before histopathogical diagnosis. Out of 380 cases, 187 cases (49.2%) had shown abnormalities on Pap smear of which 80 cases (42%) were diagnosed as atypical glandular cells and 78 cases (41.7%) were diagnosed as adenocarcinoma. The presence of glandular abnormality on Pap smear significantly correlated with the tumor type, myometrial invasion and cervical involvement on histopathology (P < .05). Cases which had higher FIGO staging also had a higher detection rate on Pap smear (P < .05). The Pap smear may help in detection of endometrial carcinoma especially in cases with type 2 endometrial carinomas, tumor with cervical involvement and/or advanced FIGO stage.


Individualised training to improve teaching competence of general practitioner trainers: a randomised controlled trial.
In Flanders an important part of training to become a general practitioner (GP) is undertaken within a general practice. This requires a GP trainer to know how to facilitate learning processes. This paper reports a study focused on the research question: Does short but individualised training of GP trainers contribute to their teaching competence? A total of 47 GP trainers were randomly divided into 2 groups of a pretest/post-test control group design. After a multiple-station teaching assessment test (MSTAT), the experimental group received a short but individualised training to improve teaching competence while the control group were given no specific programme regarding teaching competence. One year later, all participants were invited to sit the post-test. In all, 61 GP trainers participated in the pretest and 51 in the post-test; 44 GP trainers participated in both tests. Despite the large attrition, the internal validity of the experiment was preserved. Beginners gained a median score of 2.04 (on a scale of 0-5) on the first MSTAT. In the post-test, the experimental group (median = 3.12) scored significantly better on the entire test (Mann-Whitney U = 166.5, P < 0.05) compared with the control group (median = 2.84). However, the GP trainers in the control group also appeared to have made progress. General practitioners who start as GP trainers have insufficient teaching competence to guarantee good coaching of students. A personal programme leads to progress in teaching competence; however, it would seem that more time and support are necessary to allow GP trainers to gain full teaching competence. The fact that the control group made progress as well suggests that the test had an important learning effect.


Impact of DAA/water composition on PFSA ionomer conformation.
Performance of a proton exchange membrane fuel cell (PEMFC) is significantly determined by the structure and composition of the electrode layer. Electrode layers are formed from inks consisting of platinum-doped carbon black particles, perfluorosulfonic acid (PFSA) ionomer and a dispersing solvent. Interaction between these materials mainly influences suspension stability, ionomer conformation and therewith layer morphology. We characterize the interplay between a short sidechain (SSC) PFSA ionomer (Aquivion® D79-25BS) and a solvent mixture (diacetone alcohol (DAA) and water with different weight ratios) by using Hansen solubility/dispersibility parameters (HSP) and by experimental tests. It was found that HSPs are well suitable to describe the ionomer/solvent interactions. In particular, the HSP difference in terms of the hydrogen bonds is responsible for the poor affinity between ionomer and solvent at low DAA concentrations. With increasing DAA content the affinity between ionomer and solvent increases as indicated by better matching HSPs. For an ionomer concentration of 4 wt%, Aquivion always forms molecular solutions for all DAA-in-water mixing ratios. Self-organization of the ionomer molecules changes from densely packed/collapsed molecules with highly deprotonated sulfonic acid side groups at low DAA concentrations to unfolded Aquivion molecules with a low dissociation degree of the sulfonic acid groups at high DAA concentrations.


Therapeutic cardiac-targeted delivery of miR-1 reverses pressure overload-induced cardiac hypertrophy and attenuates pathological remodeling.
MicroRNAs (miRNAs) play a key role in the development of heart failure, and recent studies have shown that the muscle-specific miR-1 is a key regulator of cardiac hypertrophy. We tested the hypothesis that chronic restoration of miR-1 gene expression in vivo will regress hypertrophy and protect against adverse cardiac remodeling induced by pressure overload. Cardiac hypertrophy was induced by left ventricular pressure overload in male Sprague-Dawley rats subjected to ascending aortic stenosis. When the hypertrophy was established at 2 weeks after surgery, the animals were randomized to receive either an adeno-associated virus expressing miR-1 (AAV9.miR-1) or green fluorescent protein (GFP) as control (AAV9.GFP) via a single-bolus tail-vein injection. Administration of miR-1 regressed cardiac hypertrophy (left ventricular posterior wall thickness,; 2.32±0.08 versus 2.75±0.07 mm, P<0.001) and (left ventricular septum wall thickness, 2.23±0.06 versus 2.54±0.10 mm, P<0.05) and halted the disease progression compared with control-treated animals, as assessed by echocardiography (fractional shortening, 37.60±5.01% versus 70.68±2.93%, P<0.05) and hemodynamic analyses (end-systolic pressure volume relationship/effective arterial elastance, 1.87±0.46 versus 0.96±0.38, P<0.05) after 7 weeks of treatment. Additionally, miR-1 replacement therapy lead to a marked reduction of myocardial fibrosis, an improvement in calcium handling, inhibition of apoptosis, and inactivation of the mitogen-activated protein kinase signaling pathways, suggesting a favorable effect on preventing the maladaptive ventricular remodeling. We also identified and validated a novel bona fide target of miR-1, Fibullin-2 (Fbln2), a secreted protein implicated in extracellular matrix remodeling. Taken together, our findings suggest that restoration of miR-1 gene expression is a potential novel therapeutic strategy to reverse pressure-induced cardiac hypertrophy and prevent maladaptive cardiac remodeling.


Hypophosphatemia: an update on its etiology and treatment.
Phosphate plays a key role in several biological processes. In recent years, new insights have been obtained into the regulation of the phosphate metabolism, including a growing amount of evidence suggesting that factors other than parathyroid hormone (PTH) and vitamin D are involved in maintaining the phosphate balance. A new class of phosphate-regulating factors, the so-called "phosphatonins," have been shown to be important in phosphate-wasting diseases. However, the role of the phosphatonins in the normal human homeostasis remains to be established. The incidence of hypophosphatemia in selected patient series can be more than 20%, with clinical sequelae ranging from mild to life threatening. Only when combined with phosphate depletion does hypophosphatemia become clinically significant. The factors that are involved in the phosphate homeostasis, the pathophysiology, the relevance in patient care, the clinical manifestations, and an appropriate management of phosphate depletion are discussed in this review.


Long-term prognostic significance of ventricular arrhythmias in idiopathic dilated cardiomyopathy.
The prognostic significance of ventricular arrhythmias in idiopathic dilated cardiomyopathy is controversial. Thus, 73 patients with idiopathic dilated cardiomyopathy who had both 24-hour Holter monitoring and angiography were followed for greater than or equal to 3 years. Twenty-eight patients (38%) died, 14 patients (19%) due to pump failure and 14 patients (19%) due to sudden death. Univariate analysis revealed ventricular tachycardias as a major risk indicator, among others. However, multivariate analysis determined the major independent risk factors in the following order: patients who died from pump failure, left ventricular filling pressure, left bundle branch block, the number of beats in the longest episode of ventricular tachycardia and left ventricular ejection fraction; patients who died from sudden death, left bundle branch block and left ventricular ejection fraction, but not any form of ventricular arrhythmias. Reclassification by means of the risk factors resulted in a meaningful identification of patients who died from pump failure; however, patients who died from sudden death could not be separated from survivors. Thus, in the present study Holter monitoring was unable to distinguish between patients who died from subsequent pump failure and patients who died from subsequent sudden death.


Clinical predictors of abnormal chest CT scan findings following blunt chest trauma: A cross-sectional study.
Some surgeons believe that chest computed tomography (CT) scan should be used more prudently in management of blunt chest trauma patients. This study aimed to evaluate the clinical predictors of abnormal chest CT scan findings in trauma patients. This cross-sectional study was conducted on blunt chest trauma patients aged ≥18 years who were referred to the emergency departments of two educational hospitals and underwent chest CT scan. These patients were enrolled in the study using a non-probability sampling method. The exclusion criteria included: class III or IV hemodynamic shock, need for immediate surgical or neurosurgical interventions, penetrating trauma, lack of required information, and pregnancy. Demographic factors, accident details, trauma mechanism, vital signs, and level of consciousness in predicting abnormal chest CT scan findings were evaluated. Analysis was performed using IBM SPSS statistics 21. A total of 977 patients (male 51.5%, female 48.5%) with the mean age of (41.71 ± 14.24) years, range 18-88 years were studied; 34.2% of them with high energy trauma mechanism. With 334 (34.2%) patients had abnormal findings on chest X-ray (CXR) and 332 (34.0%) cases had an abnormal findings on chest CT scan (agreement rate was 99.4%). There was a significant correlation between male gender (p < 0.0001), GCS<15 (p < 0.0001), high energy trauma mechanism (p < 0.0001), unstable hemodynamics (p < 0.01), and clinical signs and symptoms (p < 0.0001) with chest CT findings. Chest wall deformity (odds = 8; p < 0.0001), generalized tenderness (odds = 6.6, p < 0.0001), and decreased cardiac sound (odds = 3.8, p < 0.0001) were the important and independent clinical predictors of abnormal chest CT scan findings. Based on the findings, chest wall deformity, generalized tenderness, decreased cardiac sound, distracting pain, chest wall tenderness, high energy trauma mechanism, male gender, respiratory rate > 20 breathes/min, decreased pulmonary sound, and chest wall crepitation were independent clinical predictors of abnormal chest CT scan findings following blunt trauma.


Energy expenditure, energy balance, and composition of weight gain in low birth weight infants fed diets of different protein and energy content.
The effect of energy and protein intakes on energy expenditure, energy balance, and amount and relative rate of both protein and fat deposition in new tissue was investigated in 19 low birth weight infants whose mean protein and energy intakes, respectively, were 2.24 g/kg/d and 113 kcal/kg/d (formula A, n = 8), 3.6 g/kg/d and 115 kcal/kg/d (formula B, n = 5), and 3.5 g/kg/d and 149 kcal/kg/d (formula C, n = 6). The higher energy intake (formula C) but not the higher protein intake (formula B) resulted in greater energy expenditure. Both the higher protein (formula B vs formula A) and higher energy intakes (formula C vs formula B) resulted in greater weight gain secondary, in group B, to a greater absolute rate of protein deposition and, in group C, to a greater absolute rate of fat deposition. The relative composition of the new tissue deposited reflected the proportional intakes of protein and energy. The numerical value of the protein/fat ratio (g/g) of the new tissue deposited by infants fed formulas A and C, the protein contents of which were low relative to energy contents, were similar and significantly lower than the numerical value of the protein/fat ratio of the new tissue deposited by infants fed formula B, which had a higher protein content relative to energy content. These findings suggest that the composition of weight gain is related to both the absolute amounts and the proportions of dietary protein and energy; thus, both must be considered in formulation of nutritional regimens for LBW infants.


[The practical measurement of health literacy in Hungary and in international comparison].
The study presents results of an innovative measurement of practical health literacy in international context. To show the level of practical health literacy in the Hungarian society and in international comparison. We measured practical health literacy with Newest Vital Sign test on a Hungarian national representative sample, asked from 1008 persons, between May and June, 2015 from population 16 years or older, using methodological standards of Eurobarometer. The sample is representative to the above mentioned population by gender, age, region and settlement-size. Based on Newest Vital Sign test, members of the Hungarian society have good practical health literacy. The accomplishment is inconsistent with self-reported health literacy, since it shows weak results. As low level of self-reported health literacy implies that respondents don't have daily routine in practicing their skills, we could draw people's attention to food-information, that are important and show, how to utilize them. Orv. Hetil., 2016, 157(50), 2002-2006.


Radionuclide angiography--brain and bone imaging in craniofacial fibrous dysplasia (CFD): case report.
Craniofacial fibrous dysplasia (CFD) may show arterial displacement or increased uptake during arterial, capillary, venous, and blood-pool phases of radionuclide angiography. Extensive single or multiple areas of uptake are present on brain and bone images. These findings are probably due to the highly vascular bone often found in CFD. The distribution of the areas of abnormal uptake, along with pertinent clinical history and skull radiographs, usually alllows conditions to be excluded.


Chondroblastoma of the triquetrum.
Chondroblastoma is a relatively uncommon but benign bone tumor that is typically found in a long-bone epiphysis. Reports of this type of tumor in the carpals have been rare, and even fewer cases of such tumors in the triquetrum have been reported. Here, we present classical findings of a chondroblastoma at an unusual location, the triquetrum, in an adolescent. Fat-suppressed T2*-weighted imaging revealed a hyperintense tumor matrix replacing the bony trabecula of the triquetrum, which had not been addressed in previous literature. Radiography-based differential diagnosis of a bubbly lesion in the hand of an adolescent, even in the small carpal bones, should include chondroblastoma.


Torsional vibrational modes of tryptophan studied by terahertz time-domain spectroscopy.
The low-frequency torsional modes, index of refraction, and absorption of a tryptophan film and pressed powders from 0.2 to 2.0 THz (6.6-66 cm(-1)) were measured by terahertz time-domain spectroscopy at room temperature. It was found that there were two dominated torsional vibrational modes at around 1.435 and 1.842 THz. The associated relaxation lifetimes ( approximately 1 ps) for these modes of the tryptophan molecule were measured. Using a density-functional calculation, the origins of the observed torsional vibrations were assigned to the chain and ring of the tryptophan molecule.


Evaluating the plan quality of a general head-and-neck knowledge-based planning model versus separate unilateral/bilateral models.
The implementation of knowledge-based planning (KBP) continues to grow in radiotherapy clinics. KBP guides radiation treatment design by generating clinically acceptable plans in a timely and resource-efficient manner. The role of multiple KBP models tailored for variations within a disease site remains undefined in part because of the substantial effort and number of training cases required to create a high-quality KBP model. In this study, our aim was to explore whether site-specific KBP models lead to clinically meaningful differences in plan quality for head-and-neck (HN) patients when compared to a general model. One KBP model was created from prior volumetric-modulated arc therapy (VMAT) cases that treated unilateral HN lymph nodes while another model was created from VMAT cases that treated bilateral HN nodes. Thirty cases from each model (60 cases total) were randomly selected to create a third, general model. These models were applied to 60 HN test cases - 30 unilateral and 30 bilateral - to generate 180 VMAT plans in Eclipse. Clinically relevant dose metrics were compared between models. Paired-sample t-tests were used for statistical analysis, with the threshold for statistical significance set a priori at 0.007, taking into consideration multiple hypothesis testing to avoid type I error. For unilateral test cases, the unilateral model-generated plans had significantly lower spinal cord maximum doses (12.1 Gy vs 19.3 Gy, p < 0.001) and oral cavity mean doses (20.8 Gy vs 23.0 Gy, p < 0.001), compared with the bilateral model-generated plans. The unilateral and general models generated comparable plans for unilateral HN test cases. For bilateral test cases, the bilateral model created plans had significantly lower brainstem maximum doses (10.8 Gy vs 12.2 Gy, p < 0.001) and parotid mean doses (24.0 Gy vs 25.5 Gy, p < 0.001) when compared to the unilateral model. Right parotid mean doses were lower for bilateral model plans compared to general model plans (23.8 Gy vs 24.4 Gy). The general model created plans with significantly lower brainstem maximum doses (10.3 Gy vs 10.8 Gy) and oral cavity mean doses (35.3 Gy vs 36.7 Gy) when compared with bilateral model-generated plans. The general model outperformed the bilateral model in several dose metrics but they were not deemed clinically significant. For both case sets, the unilateral and general model created plans had higher monitor units when compared to the bilateral model, likely due to more stringent constraint settings. All other dose metrics were comparable. This study demonstrates that a balanced general HN model created using carefully curated treatment plans can produce high quality plans comparable to dedicated unilateral and bilateral models.


A comparison of risk factors for human immunodeficiency virus and hepatitis B virus infections in homosexual men.
We analyzed cross-sectional data from 1062 homosexual men recruited in Baltimore during 1984, to directly compare risk factors for human immunodeficiency virus (HIV) and hepatitis B virus (HBV). Using polychotomous logistic regression, risk factor odds ratios (ORs) and 95% confidence intervals were determined for men with HIV alone, men with HBV alone, and men with both HIV and HBV, compared to seronegative men, and paired comparisons among these subgroups. Factors associated with the serologic prevalence of HIV alone and HBV alone (with respective ORs) included and receptive intercourse (HIV OR = 1.23; HBV OR = 1.12), history of gonorrhea (HIV OR = 4.58; HBV OR = 2.52), and rectal douching (HIV OR = 1.41; HBV OR = 1.20). Additional factors associated with HBV alone were years of homosexual activity (OR = 1.65), sexual activity with a person who developed acquired immunodeficiency syndrome (AIDS) (OR = 1.98), and lifetime number of male sex partners (OR = 1.25). HIV and HBV coprevalence was associated with anal receptive intercourse (OR = 1.36), history of gonorrhea (OR = 2.94), rectal douching (OR = 1.45), sexual activity with a person who developed AIDS (OR = 3.87), lifetime number of male sex partners (OR = 1.21), and the lifetime sum of sexually transmitted diseases (OR = 1.47). These findings reinforce the need for following safer-sex guidelines to prevent both infections and in the case of HBV, the prevention strategies should include vaccination.


Insulin Resistance, Hyperglycemia, and Risk of Developing Obstructive Sleep Apnea in Men and Women in the United States.
Rationale: Recent prospective studies suggest diabetes as a risk factor for the development of obstructive sleep apnea (OSA). However, the extent to which diabetes-related traits, such as hyperglycemia and insulin resistance, are related to OSA risk remains uncertain. Objectives: To examine the risk of developing OSA according to baseline concentrations of fasting insulin and hemoglobin A1c (HbA1c). Methods: Participants from four prospective U.S. cohorts were included: NHS (Nurses' Health Study; 2002-2012), NHSII (Nurses' Health Study II; 1995-2013), HPFS (Health Professionals Follow-up Study; 1996-2012), and MESA (Multi-Ethnic Study of Atherosclerosis; 2000-2012). OSA was assessed by self-reported clinical diagnosis in NHS/NHSII/HPFS and at-home polysomnography in MESA (defined as Apnea-Hypopnea Index ⩾30). Results: Of 9,283 participants with fasting insulin data, 790 (8.5%) developed OSA over 10 to 18 years of follow-up. After adjusting for sociodemographic, lifestyle, and comorbidity factors, the odds ratio for incident OSA comparing the extreme quintiles of fasting insulin was 3.59 (95% confidence interval, 2.67-4.82; P-trend < 0.0001). Of 6,342 participants with HbA1c data, 715 (11.3%) developed OSA. The comparable odds ratio for HbA1c was 2.21 (95% confidence interval, 1.69-2.89; P-trend < 0.0001). Additional adjustment for body mass index and waist circumference attenuated the associations for fasting insulin (P-trend = 0.005) and HbA1c (P-trend = 0.03). In the fully adjusted model simultaneously including both biomarkers, only fasting insulin but not HbA1c was associated with OSA risk. Conclusions: Independent of obesity, insulin resistance may play a more important role than hyperglycemia in the pathogenesis of OSA. Given the limitation of using self-reported diagnosis to exclude baseline prevalent OSA cases, additional studies are needed to further establish the temporal relationship and assess whether improving insulin resistance may reduce OSA risk.


The repertoire of human tumor-associated epitopes--identification and selection of antigens and their application in clinical trials.
In cancer patients, active immunotherapy has gained significant importance in recent years by implementation of novel substances into standard clinical care. These new drugs represent strategies which either use defined cancer associated antigens as vaccines or induce tumor-directed immune responses through generation of a general inflammatory state which has extensive autoinflammatory side effects by induction of autoreactive immune cells. Hence, the definition of suitable target antigens for immunotherapy remains a major challenge. These antigens should ideally be specific markers for individual tumors or should be at least structures overexpressed on the tumor as compared to normal cells. Recent approaches have defined algorithms and refined analytical methods for antigen identification and immunological validation that have already been evaluated in clinical studies. This article summarizes recent developments in tissue analysis on genome, transcriptome and HLA-ligandome levels and of antigen application in recent clinical vaccination trials.


Sympathoexcitation by PVN-injected bicuculline requires activation of excitatory amino acid receptors.
Acute blockade of gamma-aminobutyric acid (GABA)-A receptors in the hypothalamic paraventricular nucleus (PVN) increases mean arterial pressure (MAP), heart rate (HR), and sympathetic nerve activity (SNA). However, the underlying neural mechanisms have not been fully determined. We tested the hypothesis that responses to GABA-A receptor blockade in the PVN require activation of local ionotropic excitatory amino acid (EAA) receptors. MAP, HR, and renal SNA responses to unilateral PVN microinjection of bicuculline methobromide (BIC, 0.1 nmol) were recorded before and after ipsilateral PVN injection of either vehicle (saline), the nonselective ionotropic EAA receptor antagonist kynurenate (KYN), the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (AP5), or the non-NMDA receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium (NBQX). Responses to PVN-injected BIC were unaltered by vehicle injection. In contrast, injection of KYN (7.2 nmol; n=4) nearly abolished ABP and renal SNA responses to BIC (P<0.01) and significantly attenuated (P<0.05) HR responses as well. Similarly, graded doses of AP5 (0.6, 3, and 6 nmol) and NBQX (0.26, 1.3, and 2.6 nmol) reduced responses to PVN-injected BIC in a dose-related manner, with the 3 nmol (n=7) and 1.3 nmol (n=6) doses producing maximal effects (P<0.05). KYN, AP5, and NBQX did not affect baseline parameters. Effects of a cocktail containing AP5 (3 nmol) and NBQX (1.3 nmol) were greater (P<0.01) than either antagonist alone and were not statistically different from KYN. These data indicate that cardiovascular and renal sympathetic responses to acute GABA-A receptor blockade in the PVN require local actions of EAAs at both NMDA and non-NMDA receptors.


Characterization of pyridoxal 5'-phosphate affinity labeling of band 3 protein. Evidence for allosterically interacting transport inhibitory subdomains.
Pyridoxal 5'-phosphate (PLP) is a substrate of band 3, the erythrocyte anion transport protein. It competitively inhibits anion transport and labels two exofacial chymotryptic domains (the 17-kDa (CH17) and the 35-kDa (CH35) integral fragments). Two mol of PLP are bound/mol of each fragment at saturation. PLP labeling of both domains is competitive with chloride at constant ionic strength. Addition of DNDS (4,4'-dinitrostilbene-2,2'-disulfonate), protects PLP labeling of CH35 but exposes new, nonoverlapping sites on CH17.4,4'-Diisothiocyanostilbene-2,2'-disulfonate reduces PLP labeling to both domains with time, while NAP-taurine (N(-4-azido-2-nitrophenyl)2-aminosulfonate) has no effect on either domain. At low chloride (balance citrate) and high DNDS, we can strongly suppress CH35 labeling and selectively titrate CH17 with PLP. Correlation of fractional transport inhibition with fractional PLP covalent coverage of CH17, quantitatively follows the 1:2 correlation line indicating that full coverage of CH17 sites (which constitute half of the total PLP-labeling sites on band 3) exactly inhibits one-half of transport. PLP labeling of CH35 sites accounts for the other half of inhibition. The inhibition-labeling correlation plots are nonlinear in the absence of DNDS, indicating the presence of allosteric interactions between the domains. We conclude that CH17 and CH35 compose nonoverlapping, functionally equivalent, allosterically linked transport inhibitory subdomains on band 3.


Short-term intermittent administration of parathyroid hormone facilitates osteogenesis by different mechanisms in cancellous and cortical bone.
Intermittent administration of human parathyroid hormone (1-34)[hPTH(1-34)] induces anabolic action on the bones. To understand the mechanism underlying the early phase of hPTH(1-34)-induced anabolic action, we investigated the expression profiles of osterix and sclerostin after short-term intermittent administration of hPTH(1-34) using immunohistochemistry in adult rats. In the cancellous bone, hPTH(1-34) administration greatly increased the number of osterix-positive cells in the bone marrow on day 1, but the cells gradually decreased on days 3 and 5. Injections of hPTH(1-34) induced no significant changes in the number of sclerostin-positive osteocytes in the cancellous bone. In the cortical bone, intermittent administration of hPTH(1-34) significantly reduced the number of sclerostin-positive osteocytes. The serum sclerostin level was downregulated and the osteocalcin level was upregulated on day 5 after intermittent administration of hPTH(1-34). Intermittent hPTH(1-34) injections increased osteoblast surface, osteoid thickness, and osteoid surface in cancellous bone, but not in cortical bone. This study suggested that the increase in osterix-positive osteoprogenitors in cancellous bone and the decrease in sclerostin-positive osteocytes in cortical bone play important roles in anabolic action on osteogenesis induced by short-term administration of hPTH(1-34).


A comparison of leukocyte alkaline phosphatase and plasma estradiol measurements in the monitoring of clomiphene and gonadotropin therapy.
Leukocyte alkaline phosphatase (LAP) and plasma estradiol (E2) were measured in 56 infertile women treated with clomiphene citrate and human chorionic gonadotropin (hCG) and in 21 infertile women treated with human menopausal gonadotropin (hMG) and hCG. Plasma LAP scores were found to correlate significantly with plasma E2 levels in both clomiphene- and hMG-stimulated patients, reflecting the depdence of LAP on the level of circulating plasma estrogens. However, the plasma LAP score failed to distinguish the difference between normal stimulated and hyperstimulated cycles following hMG administration. We conclude that plasma LAP measurements have little value in monitoring ovulation induction therapy.


The impact of a clinical prediction tool (BuRN-Tool) for child maltreatment on social care outcomes for children attending hospital with a burn or scald injury.
Burns are common childhood injuries and 10-20% are associated with maltreatment. This prospective before/after study investigated the impact of introducing the BuRN-Tool (a child maltreatment clinical prediction tool), on actions taken by children's social care department (CSC). Before introduction (pre-intervention): we collected standardised data on cause and characteristics of burns, in four regional hospitals. A BuRN-Tool-score was calculated retrospectively pre-intervention and by the attending clinician post-intervention. CSC involvement and actions taken relative to BuRN-Tool-score were compared pre- and post-BuRN-Tool. Data were collected for 1688 children from 17 local authorities. The percentage that received a CSC action decreased post-BuRN-Tool (pre: 58.0%, 51/88; post: 37.5%, 33/88, p = 0.007). A greater percentage of cases with a BuRN-Tool-score of ≥ 3 had a CSC action, than those with a BuRN-Tool-score 3, pre-intervention (≥3 70.0%, 35/50; = 0.04) and post-intervention (≥3 50.0%, 21/42; = 0.01). Children with a BuRN-Tool-score ≥ 3 but no contact/referral recorded by CSC for the burn, and those who had a contact/referral but no action taken, were significantly more likely than those scoring 3 to have new CSC involvement within six months following the burn. The BuRN-Tool-score ≥ 3 has the potential to alert clinicians to maltreatment concerns.


A Stiffness-Switchable, Biomimetic Smart Material Enabled by Supramolecular Reconfiguration.
In nature, stiffness-changing behavior is essential for living organisms, which, however, is challenging to achieve in synthetic materials. Here, a stiffness-changing smart material, through developing interchangeable supramolecular configurations inspired from the dermis of the sea cucumber, which shows extreme, switchable mechanical properties, is reported. In the hydrated state, the material, possessing a stretched, double-stranded supramolecular network, showcases a soft-gel behavior with a low stiffness and high pliability. Upon the stimulation of ethanol to transform into the coiled supramolecular configuration, it self-adjusts to a hard state with nearly 500-times enhanced stiffness from 0.51 to 243.6 MPa, outstanding load-bearing capability (over 35 000 times its own weight), and excellent puncture/impact resistance with a specific impact strength of ≈116 kJ m-2 (g cm-3 )-1 (higher than some metals and alloys such as aluminum, and even comparable to the commercially available protective materials such as D3O and Kevlar). Moreover, this material demonstrates reconfiguration-dependent self-healing behavior and designable formability, holding great promise in advanced engineering fields that require both high-strength durability and good formability. This work may open up a new perspective for the development of self-regulating materials from supramolecular-scale configuration regulation.


Contact pairs of RNA with magnesium ions-electrostatics beyond the Poisson-Boltzmann equation.
The electrostatic interaction of RNA with its aqueous environment is most relevant for defining macromolecular structure and biological function. The attractive interaction of phosphate groups in the RNA backbone with ions in the water environment leads to the accumulation of positively charged ions in the first few hydration layers around RNA. Electrostatics of this ion atmosphere and the resulting ion concentration profiles have been described by solutions of the nonlinear Poisson-Boltzmann equation and atomistic molecular dynamics (MD) simulations. Much less is known on contact pairs of RNA phosphate groups with ions at the RNA surface, regarding their abundance, molecular geometry, and role in defining RNA structure. Here, we present a combined theoretical and experimental study of interactions of a short RNA duplex with magnesium (Mg2+) ions. MD simulations covering a microsecond time range give detailed hydration geometries as well as electrostatics and spatial arrangements of phosphate-Mg2+ pairs, including both pairs in direct contact and separated by a single water layer. The theoretical predictions are benchmarked by linear infrared absorption and nonlinear two-dimensional infrared spectra of the asymmetric phosphate stretch vibration which probes both local interaction geometries and electric fields. Contact pairs of phosphate groups and Mg2+ ions are identified via their impact on the vibrational frequency position and line shape. A quantitative analysis of infrared spectra for a range of Mg2+-excess concentrations and comparison with fluorescence titration measurements shows that on average 20-30% of the Mg2+ ions interacting with the RNA duplex form contact pairs. The experimental and MD results are in good agreement. In contrast, calculations based on the nonlinear Poisson-Boltzmann equation fail in describing the ion arrangement, molecular electrostatic potential, and local electric field strengths correctly. Our results underline the importance of local electric field mapping and molecular-level simulations to correctly account for the electrostatics at the RNA-water interface.


Expression of soluble and fully functional ricin A chain in Escherichia coli is temperature-sensitive.
Linkage of ricin A chain (RA) to a cell surface binding antibody or other ligand can result in a potent cytotoxic agent. We expressed the primary sequence for RA in Escherichia coli to facilitate production and to obtain protein free of naturally occurring contaminants, i.e. ricin B chain. Differences in the level of expression and in the characteristics of the expressed protein were noted when several different host/vector systems were tested. Recombinant RA (rRA) was expressed directly under control of the phage lambda major leftward promoter (PL) and the E. coli trp promoter. It was also expressed fused to E. coli alkaline phosphatase sequences, both in the same reading frame for secretion and out-of-reading frame for expression in a cistron-like arrangement. Expression in the PL promoter system, which is temperature-regulated, was achieved at 37 degrees C as well as at 42 degrees C. The protein expressed at these different temperatures had grossly different properties. Whereas rRA expressed at 37 degrees C was soluble and fully active, that produced at 42 degrees C was aggregated, insoluble, and reduced in activity. Soluble rRA could be converted to the insoluble form by incubation at 42 degrees C in vivo, but not in vitro. Hence, this difference in properties does not simply reflect an inherent thermal instability of the protein. Conditions present in vivo, including the possible association with other proteins, are apparently required for this effect on rRA.


Characterization of supraspinal vasomotor pathways and autonomic dysreflexia after spinal cord injury in F344 rats.
Cardiovascular dysfunction usually occurs after high thoracic and cervical spinal cord injury (SCI). The disruption of supraspinal vasomotor pathways (SVPs) results in the loss of bulbospinal regulation of sympathetic preganglionic neurons, leading to hypotension and compensatory tachycardia at rest. Episodic autonomic dysreflexia can develop upon sensory stimulation below the level of injury. In rodents, the precise spatial distribution of SVPs in the spinal cord originating from the rostral ventrolateral medulla (RVLM) has not been fully defined. To facilitate future studies of axon regeneration to regain cardiovascular control, we injected biotinylated dextran amine (BDA) bilaterally into the RVLM to anterogradely trace SVPs in Fischer 344 (F344) rats. Three weeks later, BDA-labeled descending projections were predominantly localized within the dorsolateral funiculus throughout the cervical and thoracic spinal segments as expected. Additionally, BDA-labeled fibers were also observed in ventral white matter. After a T4 dorsal hemisection to interrupt the dorsolateral funiculus, BDA labeled terminals originating from the ventral white matter as well as serotonergic projections were still detected in regions of autonomic nuclei below the injury. Based on these results, we examined cardiovascular responses after different lesions at spinal level T4, including lateral or dorsal hemisection, dorsolateral or complete transection. Hemodynamic dysfunction and autonomic dysreflexia were only elicited in rats with complete T4 transections when all SVPs were disrupted. Hence, F344 rats with complete T4 transections provide a reliable model for investigating means to improve cardiovascular functional recovery after SCI.


Diagnostic tools assessing airway remodelling in asthma.
Asthma is an inflammatory disease of the lower airways characterised by the presence of airway inflammation, reversible airflow obstruction and airway hyperresponsiveness and alterations on the normal structure of the airways, known as remodelling. Remodelling is characterised by the presence of metaplasia of mucous glands, thickening of the lamina reticularis, increased angiogenesis, subepithelial fibrosis and smooth muscle hypertrophy/hyperplasia. Several techniques are being optimised at present to achieve a suitable diagnosis for remodelling. Diagnostic tools could be divided into two groups, namely invasive and non-invasive methods. Invasive techniques bring us information about bronchial structural alterations, obtaining this information directly from pathological tissue, and permit measure histological modification placed in bronchi layers as well as inflammatory and fibrotic cell infiltration. Non-invasive techniques were developed to reduce invasive methods disadvantages and measure airway remodelling-related markers such as cytokines, inflammatory mediators and others. An exhaustive review of diagnostic tools used to analyse airway remodelling in asthma, including the most useful and usually employed methods, as well as the principal advantages and disadvantages of each of them, bring us concrete and summarised information about all techniques used to evaluate alterations on the structure of the airways. A deep knowledge of these diagnostic tools will make an early diagnosis of airway remodelling possible and, probably, early diagnosis will play an important role in the near future of asthma.


Benign congenital muscular dystrophy with autosomal dominant heredity: problems of classification.
A family with autosomal dominant congenital muscular dystrophy affecting members of both sexes in three generations is described; a father and his two sons were studied. The onset of symptoms was in early childhood and progression, if any, was slow. The proximal limb muscles, the sternocleidomastoid and anterior tibial muscles were affected. One patient had torticollis and all had heel-cord shortening. An electrophysiological examination showed myopathy. There was no cardiomyopathy. Creatine kinase (CK) was elevated, and a histological study revealed a necrotizing myopathy with pronounced regeneration and formation of aberrant myofibrils (ringbinden) and fibrosis.


Loneliness trajectories.
This special section brings together five studies using group-based modeling to capture developmental trajectories of loneliness from age 7 through age 20. Together, the findings from these studies provide further evidence that developmental trajectories of loneliness are likely not best understood at a continuum but reflect distinct subpopulations that differ both where they start out and how they change over time in terms of mean levels of loneliness. Furthermore, adolescents who show chronically high loneliness or increasing loneliness over time exhibit poorer psychological and physical health, including greater incidence of depressive symptoms and more frequent suicide attempts. The findings from these studies also suggest that individuals experiencing increases in loneliness with age fare worse as well in terms of both physical and psychological health.


Using a hierarchical approach to investigate residual auditory cognition in persistent vegetative state.
Persistent vegetative state is arguably one of the least understood and most ethically troublesome neurological conditions in modern medicine. The term describes a rare disorder in which patients who emerge from coma appear to be awake, but show no signs of awareness. In recent years, a number of studies have demonstrated an important role for functional neuroimaging in the identification of residual cognitive function in patients meeting the clinical criteria for persistent vegetative state. Such studies, when successful, may be particularly useful where there is a concern about the accuracy of the diagnosis and the possibility that residual cognitive function has remained undetected. Unfortunately, functional neuroimaging in persistent vegetative state is extremely complex and subject to numerous methodological, clinical and theoretical difficulties. In this chapter, we argue that in order to most effectively define the degree and extent of preserved cognitive function in persistent vegetative state, a hierarchical approach to cognition is required. To illustrate this point, a series of functional neuroimaging paradigms in the auditory domain are described, which systematically increase in complexity in terms of the auditory and/or linguistic processes required and, therefore, the degree of preserved cognition that can be inferred from "normal" patterns of activation in persistent vegetative patients. Preliminary results in a small series of patients provide a strong basis for the systematic study of possible residual cognitive function in persistent vegetative state.


Emergency surgery for obstructed colorectal cancer in Vietnam.
The benefit of one-stage surgery in emergency surgery for obstructing colorectal cancer (oCRC) by colorectal surgeons has increased during the last century but little is known about the outcomes of this technique conducted by general surgeons in developing countries. This retrospective study was to evaluate the outcomes of emergency surgery for oCRC in a general surgery unit. A retrospective review of data from 1175 patients who underwent colorectal surgery between January 2013 and January 2018 was performed. Among these, a total of 186 patients with oCRC who underwent surgery within 24 h of hospital admission were analyzed. For patients with resectable right-sided oCRC, one-stage surgery was performed. For left-sided oCRC, primary anastomosis was mainly attempted; otherwise, a stoma was formed. The rates of primary resection, PRa, stoma, mortality, and morbidity were evaluated. Among 186 patients, oCRC involving the right colon, left colon, and rectum were found in 33.3%, 59.1% and 7.5% respectively. Primary resection and anastomosis were performed in 100%, 44.7%, and 0% of patients with oCRC in the right colon, left colon, and rectum respectively. The complication incidence based on Clavien-Dindo grade III or higher was 16.1% and the mortality rate was 7.5%. The median length of hospital stay was 8.5 days, ranging from 2 to 70 days. General surgeons with colorectal surgery experience can still manage oCRC effectively. Primary resection and anastomosis for left-sided oCRC is safe in selective patients. The emergency surgery for oCRC could be benefit with the participation of colorectal surgeons.


The afferent innervation of the thymus gland in the rat.
The afferent nervous supply to the thymus gland has been investigated by means of the retrograde transport of horseradish peroxidase. It has been shown that the thymus receives an afferent supply from the nodose ganglia of the vagus and from the dorsal root ganglia C1-C7. The afferent innervation of the right and left thymic lobes is bilaterally organized; the fibers of a small celled population of nodose ganglion neurons cross outside the thymus and those of a larger celled population cross within the thymus gland. The functional implications of these findings are discussed in the context of central nervous system-immune system interactions.


A caution regarding lymphatic mapping in patients with colon cancer.
The value of lymphatic mapping and sentinel lymph node biopsy in the treatment of colon cancer is controversial. The purpose of this study was to determine the accuracy of lymphatic mapping in patients with colon cancer. Forty-eight patients with colon cancer underwent lymphatic mapping and sentinel lymph node biopsy using isosulfan blue dye followed by standard surgical resection. The sentinel lymph nodes underwent thin sectioning as will as immunohistochemical staining for cytokeratin, in addition to standard hematoxylin and eosin staining. In 47 (98%) patients, a sentinel lymph node was identified. Sixteen patients had lymph nodes containing metastatic disease, and in 6 patients the sentinel lymph node was positive for disease. In no patient was the sentinel lymph node the only site of metastatic disease. In 10 patients the sentinel lymph node was negative for disease, whereas the nonsentinel lymph nodes contained metastatic disease (false negative rate = 38%). The role of lymphatic mapping and sentinel lymph node biopsy in colon cancer is not as clear as its role in other tumors. Further large prospective studies are needed to evaluate the accuracy and potential benefit of this procedure in patients with colon cancer.


Nested and multiplex polymerase chain reactions for the identification of bluetongue virus infection in the biting midge, Culicoides variipennis.
Two polymerase chain reaction tests for the detection of bluetongue viral (BLU) RNA in the principal North American insect vector, Culicoides variipennis, were developed. The BLU serogroup specific test used the highly expressed non-structural protein 1 gene as the target gene and two amplification steps. First a 1228 base pair product was amplified using an outer primer pair, then a second amplification using a nested or internal primer pair produced a 930 base pair product. This nested PCR test was found to be very sensitive detecting an equivalent to 1 plaque-forming unit of BLU viral RNA extracted from infected biting midges. The serotype specific test used a multiplex PCR approach in which five different primer pairs were used simultaneously. Each pair was based on the variable outer capsid protein VP2 gene of the five US serotypes generating specific product which were easily identified by size difference. The sensitivity of the multiplex PCR was less sensitive than the nested-PCR but sufficient for use with field collected samples. These tests provide valuable tools for epidemiologic studies of BLU disease.


Acetabular Liner Dissociation: A Comparative Study of Two Contemporary Uncemented Acetabular Components.
There are a number of reports of polyethylene liner dissociation of third-generation modular acetabular components. This study compares our experience with 2 contemporary systems to determine whether this is an implant- or class-specific problem. This is a single-center retrospective study of 961 primary total hip arthroplasties using 2 third-generation modular cementless acetabular shells: Pinnacle (535) and R3 (426) with a polyethylene liner. Details of all revisions were obtained from local databases and the New Zealand Joint Registry. Kaplan-Meier survival curves were calculated for all-cause revision, acetabular reoperation (including liner exchange), and liner dissociation. There were 17 revisions in group 1 (Pinnacle; DePuy Synthes): 17 for recurrent dislocation, 6 for liner dissociations (1.12%), 3 for femoral loosening, and one for deep infection. In group 2 (R3; Smith and Nephew), there were 4 revision procedures: one for infection, 2 for dislocation, and one femoral revision for periprosthetic fracture. There were significantly higher proportions revised in group 1 for all-cause revision, acetabular reoperation, and dissociation (P = .024 to 0.038). The 7-year survival for all-cause revision was 96.1% for Pinnacle and 99.0% for R3 (P = .022), and that in the acetabular reoperation group was 96.9% for Pinnacle and 99.3% for R3 (P = .035). There was a higher revision rate for the Pinnacle acetabular component than for the R3 at 7 years. This was mainly due to polyethylene liner dissociation that can occur early or late. It appears to be a problem specific to the Pinnacle cup design rather than a feature of similar third-generation acetabular components.


Focus on the 9th Annual Seminar organized by the Canceropôle Provence-Alpes-Côte-d'Azur: Highlights of the event.
The 9th Annual Seminar of the Canceropôle Provence-Alpes-Côte-d'Azur took place on July, 5th-6th 2022 in Saint-Raphaël, south of France. Annual meeting of the regional scientific community working in the field of cancer research, this seminar brings together a large and diverse audience, with 285 people attending in 2022: PhD students, postdocs, PIs (Principal Investigators) and senior researchers, clinicians, patient associations, funding partners of the Canceropôle. This document reviews the major scientific results presented and key moments of the event.


Detection of bovine herpesvirus 1 in cumulus-oocyte complexes of cows.
Bovine herpesvirus 1 (BoHV-1) is the causative agent of infectious bovine rhinotracheitis (IBR) and is also associated with reproductive failure. This study investigated the presence of BoHV-1 in cumulus-oocyte complexes (COCs) of naturally-infected cows without clinical signs of IBR. The presence of BoHV-1 in COCs was evaluated by immunofluorescence using confocal laser scanning microscopy. Blood samples and ovaries from 82 cows that had not been vaccinated against BoHV-1 were collected for serological analysis. COCs were divided into two pools: COCs derivate from seropositive cows and from seronegative cows. Then, the samples were processed for confocal microscopy analysis. The results indicated that 61% (50/82) of cows were seropositive for BoHV-1. A total of 719 COCs were obtained from the cows and processed. None of 276 COCs from the 32 seronegative cows presented BoHV-1. However, BoHV-1 was present in the cytoplasm of cumulus cells from 158 out of 443 COCs aspirated from the seropositive cows. The detection of BoHV-1 in the COCs of seropositive cows suggests that the COCs of naturally-infected, asymptomatic cows may be infected with BoHV-1.


The analysis of recombinant interleukin-2 by thermospray liquid chromatography-mass spectrometry.
The complete sequence of recombinant human interleukin-2 expressed in Escherichia coli has been confirmed by thermospray liquid chromatography-mass spectrometry (TS-LC-MS) of a tryptic digest derived from 100 micrograms (7 nmol) of reduced carboxymethylated interleukin-2. The preparation was shown by this method to contain predominantly unprocessed N-terminal initiator Met, with some authentic N-terminal Ala; the rest of the protein was as predicted from the DNA sequence, though some deamidated material was noted. TS-LC-MS proved to be a rapid and efficient method for surveying the protein tryptic peptide products allowing all the data to be collected in one chromatographic run; all tryptic fragments were identified by their molecular ions including those for the larger peptides (Mr 1500-3500) which, due to the presence of doubly and triply charged molecular ions, were brought within the mass range of the instrument (1800 Da). It is proposed that TS-LC-MS is a good general method for analyzing recombinant protein digests with respect to sequence confirmation, processing, and post-translational modification, and since each chromatographic peak is identified allows for subsequent monitoring of the protein by LC using uv detection. The method suffers from the disadvantages that all the sample is consumed during the experiment and that no fragment (sequence) ions are generally observed.


Evaluation the binding of chelerythrine, a potentially harmful toxin, with bovine serum albumin.
Chelerythrine (CHE), a benzophenanthridine alkaloid, is usually used as a nutritional and functional additive in variety of health foods. However, it should be paid enough attention because of its potential toxicity to human health. In this work, the binding mechanism of CHE with bovine serum albumin (BSA) was systematically investigated with spectroscopic approaches. The results showed that the mixture of BSA with CHE could spontaneously cause the formation of BSA-CHE complex through electrostatic interaction under simulative physiological conditions (0.01 mol L-1 Tris-HCl, 0.015 mol L-1 NaCl, pH = 7.4). Site marker competitive displacement experiments exhibited that CHE was primarily bound to the hydrophobic pocket of the site II (subdomain IIIA) of BSA. It has been reported that the binding of small functional molecules to serum albumins remarkably impacts their absorption, distribution, metabolism, conformation, and excretion features. Therefore, this study might be helpful for human to have an in-depth understanding of the biological effect of CHE in vivo and guide human to take it safely and reasonably.


Influence of H1- and H2-receptor antagonists on the circulatory system and on the endogenous plasma histamine concentrations in dogs.
The effects of the H1-receptor antagonist dimethpyrindene and the H2-receptor antagonist burimamide on circulatory and respiratory parameters and on plasma histamine levels were tested in 21 mongrel dogs. Both drugs released histamine. The incidence for this effect was 10/11 in the case of dimethpyrindene and 5/10 in the case of burimamide. Following dimethpyrindene all animals showed arterial hypotension, pulmonal hypertension, decrease in peripheral resistance and hyperventilation. The portal venous pressure was increased in dogs reacting by a histamine release. Following burimamide both an initial arterial hypertension and a subsequent hypotension were observed the latter being more pronounced in the group with histamine release. In this group the portal venous pressure raised considerably. In the non-reacting animals cardiac output was elevated, probably due to a release of catecholamines. It seemed remarkable that the effect of exogenous histamine on portal venous pressure was completely blocked by dimethpyrindene, but not the action of histamine released by the drug itself. It is concluded that the effects of anti-histaminic drugs on possibly histamine-induced physiological and pathophysiological processes should be interpreted very carefully as far as their specificity is concerned.


Biological activities of Wiedemannia multifida (Linnaeus) Bentham and Wiedemannnia orientalis Fisch. & Mey.
To evaluate total phenolic, antioxidant and antimicrobial activities of methanolic extracts of the Wiedemannia multifida (W. multifida) and Wiedemannnia orientalis (W. orientalis). Phosmomolybdenum assay, DPPH radical scavenging activity and β-carotene-linoleate bleaching were used to evaluate the antioxidant capacity. The total phenolics were found to be (22.45±0.60) and (9.53±0.00) mg gallic acid equivalents (GAE)/g in W. multifida and W. orientalis extracts, respectively. The predominant phenolic compounds identified by HPLC-DAD in the both extracts were rutin+ellagic acid and kaempferol. Total antioxidant capacity and DPPH radical scavenging activity of W. multifida were higher than W. orientalis. In β-carotene-linoleic acid system, both extracts exhibited strong inhibition against linoleic acid oxidation. Antimicrobial activity was assessed by the agar diffusion method against fifteen microorganisms. Both extracts exhibited remarkable antibacterial activity. The present study suggests that methanolic extracts of W. multifida and W. orientalis could be a good source of antioxidant and antimicrobial agents in foods, pharmaceuticals preparations.


Isolation and in silico characterization of novel esterase gene with β-lactamase fold isolated from metagenome of north western Himalayas.
An esterase-producing clone Aph2 was isolated from the Apharwat soil metagenomic library, a mountain peak in NW Himalayas. ORF 2 (Est Ac) of clone Aph2 corresponds to 271 aa protein and showed 26 % sequence similarity to carboxylesterase gene of Synechococcus sp. JA-2-3B. Est Ac contains nucleophilic Ser in S68-X-X-K71 motif of β-lactamases with Tyr Y103. The conserved sequences are common with family VIII carboxylesterase and class C β-lactamase sequences. Phylogenetic analysis revealed that Est Ac sequence is closely related to esterase than to β-lactamases. In silico 3D protein structure of Est Ac was generated using MODELLER software (9.10 version). Model was generated on the basis of carboxylesterase template (PDB:1CI8) of Est B (Burkholderia gladioli) and the stereochemical parameters of the model generated were satisfactory. Docking with diisopropyl-fluorophosphate confirmed catalytic activity of Ser68 present in S-X-X-K motif.


Clinical outcomes of multiple myeloma patients who undergo autologous hematopoietic stem cell transplant with G-CSF or G-CSF and plerixafor mobilized grafts.
Impact of Plerixafor (P) mobilized stem cells on immune reconstitution, such as absolute lymphocyte count at day 30 (ALC30), and on long-term outcomes of Multiple Myeloma (MM) patients undergoing autologous stem cell transplant (ASCT) has not been well established. We evaluated total of 469 patients mobilized with G-CSF (G) alone, and 141 patients mobilized with G-CSF plus plerixafor (G+ P). Patients only received plerixafor if they had peripheral blood CD34+ blood count <20/μL on first planned day of collection. Primary endpoint, ALC30, was 1.3 K/μL (range, 0.1-4.5) and 1.2 K/μL (range, 0.1-5.1) for G and G + P, respectively (P =. 61). The median PFS was 2.5 years (95% CI, 2.1-3.2) and 2.8 years (95% CI, 2.0-3.3) for G and G + P, respectively (HR: 1.13; 95% CI, 0.84-1.50; P = .42). The median OS was 6.1 years (95% CI, 4.6-NR) for G group compared to 3.7 years (95% CI, 3.2-NR) for the G + P group (HR: 1.64; 95% CI, 1.12-2.40; P = .01). The median follow-up time for OS was 2.53 years (95% CI, 2.13-2.99) and 1.59 years (95% CI, 1.17-2.02) for G and G+ P group, respectively. In this large retrospective analysis of MM patients mobilized with G-CSF vs G-CSF + P, there was no significant difference in lymphocyte recovery or PFS. There was an overall survival difference in patients who were poor mobilizers and could not be mobilized with G-CSF alone.


Aorta-coronary bypass grafting with the internal mammary artery: clinical experience in 70 patients.
Clincal and angiographic results in 70 patients who received free internal mammary artery (IMA) grafts are reviewed. One postoperative death occurred, but it was not related to the free IMA technique. Forty-seven patients underwent postoperative arteriography. The average interval between operation and catheterization was 10.7 months, and the patency rate for 49 free IMA grafts was 89.8 per cent. Of the 29 patients who recieved free IMA grafts as the only revascularization procedure, 21 patients (80 per cent) progressed to Functional Class I and only 5 patients did not have improvement in their functional status.


Epidemiology of infections due to nonpigmented rapidly growing mycobacteria diagnosed in an urban area.
The objective was to determine the incidence, clinical significance, and epidemiology of the isolates of nonpigmented, rapidly growing mycobacteria (NPRGM) in Madrid, Spain. Patients with new isolates of NPRGM during 2005 were selected prospectively for review of clinical charts. Clinical significance was analyzed according internationally accepted criteria. Randomly amplified polymorphic DNA (RAPD) was used for the genotyping of the isolates. NPRGM were identified in 70 patients (1.51 cases/100,000 inhabitants). The species were M. abscessus (in 5 patients), M. chelonae (in 9), M. fortuitum (in 40), M. peregrinum (in 9), M. mageritense (in 5), M. mucogenicum (in 2), and M. alvei (in 1 patient). The isolates were clinically significant in 17 cases (24.3%, 0.39 cases/100,000 inhabitants): in 4 cases of M. abscessus, in 5 of M. chelonae, and in 9 of M. fortuitum. Only 10.7% of the respiratory isolates were significant, whereas 75% of the nonrespiratory ones were significant (p < 0.001). RAPD analysis showed no relationship among the 74 strains available for the study. No characteristic resistance pattern could be found, although 4 strains appeared to be resistant to amikacin. Significant isolates were mainly nonrespiratory ones. The most significant species was M. abscessus. No relationship between the various isolates was detected, ruling out interhuman transmission between these cases.


Laryngeal Anaplastic Lymphoma Kinase-Positive B-cell Lymphoma: Case Report and Review.
Larynx is an uncommon extranodal site for non-Hodgkin lymphoma (NHL). Anaplastic lymphoma kinase (ALK)-positive B-cell lymphoma is a rare and aggressive form of NHL. A 19-year-old male presented to the ENT department with globus sensation, hoarseness, cervical lymphadenopathy and weight loss. A 70-degree rigid endoscopic examination of the larynx showed a vascular, irregular, submucosal mass arising from the right aryepiglottic fold causing near complete obstruction of the laryngeal airway. PET-CT showed hypermetabolic lesions in the supraglottis, cervical lymph nodes, cervical spine, ribs and abdominal lymph nodes. Biopsy was taken from the supraglottic mass as well as the enlarged cervical lymph nodes, which revealed ALK-positive large B-cell NHL. In this report, we present a rare case of ALK-positive large B-cell NHL of the larynx, discussing its clinical, radiological and pathological features. A limited review of literature is also presented. There is a need to develop a database for the description of lymphomas affecting the larynx and this case report adds to the existing knowledge of this rare entity.


The pharmacological and anatomical substrates of the amphetamine response in the rat.
Bilateral 6-hydroxydopamine microinjections into the substantia nigra abolished both the locomotor and stereotyped responses to d-amphetamine in adult rats. The lesions resulted in a depletion of over 99 per cent of striatal tyrosine hydroxylase activity (indicating a near total lesion of the nigro-striatal dopamine pathway) as well as severe noradrenaline depletions. However, lesion of the dorsal or ventral noradrenergic pathways resulted in similar noradrenaline depletions but with no effect on striatal tyrosine hydroxylase levels and without the concomitant blockage of the amphetamine response. The substantia nigra lesioned rats were behaviourally supersensitive to apomorphine and L-DOPA and did not show a locomotor response to cocaine. The substantia nigra lesioned rats were not aphagic or adipsic. It was concluded that both the locomotor and stereotyped responses induced by amphetamine are dependent on the functional integrity of the nigro-striatal dopamine pathway.


Metal hypersensitivity screening among frontline healthcare workers-A descriptive study.
The study aims were to (a) assess allergy screening practices, (b) determine the awareness of metal hypersensitivity among frontline healthcare workers and (c) examine perceived barriers to implementing metal hypersensitivity screening into clinical practice. Adverse device-related events, such as hypersensitivity to metals, are well documented in the literature. Hypersensitivity to metal is a type IV T-cell-mediated reaction that can occur after cardiac, orthopaedic, dental, gynaecological and neurosurgical procedures where a device with metal components is implanted into the body. Patients with hypersensitivity to metal are likely to experience delayed healing, implant failure and stent restenosis. Identifying patients with a history of metal hypersensitivity reaction could mitigate the risk of poor outcomes following device implant. Yet in clinical practice, healthcare workers do not routinely ask about the history of metal hypersensitivity when documenting allergies. The existing literature does not report why this is not included in allergy assessment. Following the STROBE checklist, a cross-sectional, descriptive study was conducted. Frontline healthcare workers were recruited using professional contacts and social online media to complete an online questionnaire. Quantitative data were summarised descriptively while thematic analysis was used to examine barriers to implementation. Three hundred forty-five participants from 14 countries completed the questionnaire, with the majority (187/54%) practicing in Canada, in general medicine and intensive care units. Ninety per cent of the participants did not routinely ask about metal hypersensitivity when evaluating allergy history. Of the respondents, 86% were unaware of the association between metal hypersensitivity and poor patient outcomes. After presented with the evidence, 81% indicated they were likely or very likely to incorporate the evidence into their clinical practice. Common themes about barriers to implementing were 'Standards of Practice', 'Knowledge' and 'Futility of Screening'. The findings suggest lack of awareness as the main reason for not including metal in routine allergy assessment.


Beneficial effect of rice bran extract against 3-nitropropionic acid induced experimental Huntington's disease in rats.
Huntington's disease (HD) is a neurodegenerative disorder, characterized by progressive motor and non-motor dysfunction due to degeneration of medium spiny neurons in striatum. 3-Nitropropionic acid is commonly used to induce the animal model of HD. Rice bran is supposed to have beneficial effects on mitochondrial function. The present study has been designed to explore the effect of rice bran extract against 3-Nitropropionic acid induced neurotoxicity in rats. 3-Nitropropionic acid (10 mg/kg, i.p) was administered systemically for 21 days. Hexane and ethanol extract of rice bran were prepared using Soxhlation. Hexane (250 mg/kg) and ethanol extract (250 mg/kg) were administered per os for 21 days in 3-NP treated groups. Behavioral parameters (body weight, grip strength, motor coordination, locomotion) were conducted on 7th, 14th and 21st day. Animals were sacrificed on 22nd day for biochemical, mitochondrial dysfunction (Complex II), neuroinflammatory and neurochemical estimation in striatum. This study demonstrates significant alteration in behavioral parameters, oxidative burden (increased lipid peroxidation, nitrite concentration and decreased glutathione), mitochondrial function (decreased Complex II enzyme activity), pro-inflammatory mediators and neurochemical levels in 3-nitropropionic acid treated animals. Administration of hexane and ethanol extract prevented the behavioral, biochemical, neuroinflammatory (increased TNF-α, IL-1β and IL-6) and neurochemical alterations (decreased dopamine, norepinephrine, serotonin, 5-hydroxy indole acetic acid, GABA and increased 3,4-dihydro phenyl acetaldehyde, homovanillic acid and glutamate levels) induced by 3-nitropropionic acid. The outcomes of present study suggest that rice bran extract is beneficial and might emerge as an adjuvant or prophylactic therapy for treatment of HD like symptoms.


Elastic properties of polyelectrolyte capsules studied by atomic-force microscopy and RICM.
Mechanical properties of polyelectrolyte multilayer capsules were studied using a new method combining atomic-force microscopy and reflection interference contrast microscopy. By measuring the force vs. deformation for poly(styrene sulfonate)/poly(allylamine) capsules the existence of different deformation regimes depending on the applied deformation was shown. The present paper focuses on the small-deformation regime. The elastic response of the deformed capsule was studied as a function of the wall thickness and the capsule size, and showed the theoretically expected variations. The Young modulus obtained from the experiments ranges between 1.3 and 1.9 GPa.


Correction: Eriodictyol: a review of its pharmacological activities and molecular mechanisms related to ischemic stroke.
Correction for 'Eriodictyol: a review of its pharmacological activities and molecular mechanisms related to ischemic stroke' by Sa Guo et al., Food Funct., 2023, 14, 1851-1868, https://doi.org/10.1039/D2FO03417D.


Effects of change in streamflow patterns on water quality.
Streamflow patterns are closely linked with the quality of stream water, but they are often dealt separately. Due to this, the effects of change in streamflow patterns resulting from river regulation and flow diversion on stream water quality remain under-investigated. This study models change in water quality indicators including pollutants (total suspended solids and turbidity), nutrients (total nitrogen and phosphorus), dissolved oxygen, nitrogen (kjeldahl), pH, and salinity caused by the change in streamflow patterns under different scenarios of river regulation, flow diversion, and rainfall. The generalized additive model was used and the Goulburn-Broken catchment, Australia was chosen as the case study. It was found that concentrations of pollutants and nutrients increased by 38% while dissolved oxygen and nitrogen (kjeldahl) decreased by 35% during the period 1990-2018. These changes were associated with an average increase of 20% in low and medium flows, an average decline of 22% in high and overbank flows and a 15% decline in rainfall. Under the scenario of climate change, river regulation and flow diversion, the overbank flow patterns would mimic the effects of low and medium flows on the water quality indicators that would raise the concentration of pollutants, nutrients, and salinity by 19%. Restoration of high flows would decrease these concentrations by 28% relative to current concentrations, however, it would also reduce dissolved oxygen, nitrogen (kjeldahl), and pH. Effects of streamflow patterns on water quality have implications for environmental flow management, thus, this study recommends critical adjustments in low, medium, and high flows for improving water quality.


The anatomy, movement, and functions of human sperm tail: an evolving mystery.
Sperms have attracted attention of many researchers since it was discovered by Antonie van Leeuwenhoek in 1677. Though a small cell, its every part has complex structure and different function to play in carrying life. Sperm tail is most complicated structure with more than 1000 proteins involved in its functioning. With the advent of three-dimensional microscopes, many studies are undergoing to understand exact mechanism of sperm tail movement. Most recent studies have shown that sperms move by spinning rather than swimming. Each subunit of tail, including axonemal, peri-axonemal structures, plays essential roles in sperm motility, capacitation, hyperactivation, fertilization. Furthermore, over 2300 genes are involved in spermatogenesis. A number of genetic mutations have been linked with abnormal sperm flagellar development leading to motility defects and male infertility. It was found that 6% of male infertility cases are related to genetic causes, and 4% of couples undergoing intracytoplasmic sperm injection for male subfertility have chromosomal abnormalities. Hence, an understanding of sperm tail development and genes associated with its normal functioning can help in better diagnosis of male infertility and its management. There is still a lot that needs to be discovered about genes, proteins contributing to normal human sperm tail development, movement, and role in male fertility. Sperm tail has complex anatomy, with surrounding axoneme having 9 + 2 microtubules arrangement along its entire length and peri-axonemal structures that contribute in sperm motility and fertilization. In future sperm tail-associated genes, proteins and subunits can be used as markers of male fertility.


Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI.
Standardization is an important milestone in the validation of DWI-based parameters as imaging biomarkers for renal disease. Here, we propose technical recommendations on three variants of renal DWI, monoexponential DWI, IVIM and DTI, as well as associated MRI biomarkers (ADC, D, D*, f, FA and MD) to aid ongoing international efforts on methodological harmonization. Reported DWI biomarkers from 194 prior renal DWI studies were extracted and Pearson correlations between diffusion biomarkers and protocol parameters were computed. Based on the literature review, surveys were designed for the consensus building. Survey data were collected via Delphi consensus process on renal DWI preparation, acquisition, analysis, and reporting. Consensus was defined as ≥ 75% agreement. Correlations were observed between reported diffusion biomarkers and protocol parameters. Out of 87 survey questions, 57 achieved consensus resolution, while many of the remaining questions were resolved by preference (65-74% agreement). Summary of the literature and survey data as well as recommendations for the preparation, acquisition, processing and reporting of renal DWI were provided. The consensus-based technical recommendations for renal DWI aim to facilitate inter-site harmonization and increase clinical impact of the technique on a larger scale by setting a framework for acquisition protocols for future renal DWI studies. We anticipate an iterative process with continuous updating of the recommendations according to progress in the field.


Hyaluronic acid-shelled, peptide drug conjugate-cored nanomedicine for the treatment of hepatocellular carcinoma.
Peptide-drug conjugate (PDC) is a promising prodrug in drug delivery systems. To fabricate nanostructures with proper molecular design which can self-assemble to spherical morphologies is very important for PDC chemotherapy. In this study, a novel PDC (PDC-DOX2), in which two doxorubicin (DOX) molecules are conjugated onto a short peptide (KIGLFRWR) with self-assembly function, was designed and synthesized. PDC-DOX2 with self-assembly properties forms a spherical structure under hydrophobic interaction in water. Hyaluronic acid (HA) was then coated on PDC-DOX2 micelles to form a HA-shelled, peptide-doxorubicin conjugate-cored nanomedicine (HA@PDC-DOX2). The amount of HA can regulate the particle size and stabilization of HA@PDC-DOX2. In addition, HA can actively enhance the targeting effects of PDC-DOX2 micelles since it can interact with overexpressed receptors in cancer cells. The core-shell structured HA@PDC-DOX2 nanomedicine showed significantly enhanced potency against hepatocellular carcinoma compared to PDC-DOX2 micelles as well as free DOX. In this work, a novel PDC which can self-assemble to spherical morphologies and a core-shell structure HA@PDC-DOX2 nanomedicine are designed and prepared. It provides a convenient strategy for the size control of PDC assemblies and constructs effective PDC-based drug delivery systems for cancer treatment.


Long-Term Effects of a Very Low Carbohydrate Compared With a High Carbohydrate Diet on Renal Function in Individuals With Type 2 Diabetes: A Randomized Trial.
To compare the long-term effects of a very low carbohydrate, high-protein, low saturated fat (LC) diet with a traditional high unrefined carbohydrate, low-fat (HC) diet on markers of renal function in obese adults with type 2 diabetes (T2DM), but without overt kidney disease.One hundred fifteen adults (BMI 34.6 ± 4.3 kg/m, age 58 ± 7 years, HbA1c 7.3 ± 1.1%, 56 ± 12 mmol/mol, serum creatinine (SCr) 69 ± 15 μmol/L, glomerular filtration rate estimated by the Chronic Kidney Disease Epidemiology Collaboration formula (eGFR 94 ± 12 mL/min/1.73 m)) were randomized to consume either an LC (14% energy as carbohydrate [CHO < 50 g/day], 28% protein [PRO], 58% fat [<10% saturated fat]) or an HC (53% CHO, 17% PRO, 30% fat [<10% saturated fat]) energy-matched, weight-loss diet combined with supervised exercise training (60 min, 3 day/wk) for 12 months. Body weight, blood pressure, and renal function assessed by eGFR, estimated creatinine clearance (Cockcroft-Gault, Salazar-Corcoran) and albumin excretion rate (AER), were measured pre- and post-intervention.Both groups achieved similar completion rates (LC 71%, HC 65%) and reductions in weight (mean [95% CI]; -9.3 [-10.6, -8.0] kg) and blood pressure (-6 [-9, -4]/-6[-8, -5] mmHg), P ≥ 0.18. Protein intake calculated from 24 hours urinary urea was higher in the LC than HC group (LC 120.1 ± 38.2 g/day, 1.3 g/kg/day; HC 95.8 ± 27.8 g/day, 1 g/kg/day), P < 0.001 diet effect. Changes in SCr (LC 3 [1, 5], HC 1 [-1, 3] μmol/L) and eGFR (LC -4 [-6, -2], HC -2 [-3, 0] mL/min/1.73 m) did not differ between diets (P = 0.25). AER decreased independent of diet composition (LC --2.4 [-6, 1.2], HC -1.8 [-5.4, 1.8] mg/24 h, P = 0.24); 6 participants (LC 3, HC 3) had moderately elevated AER at baseline (30-300 mg/24 h), which normalized in 4 participants (LC 2, HC 2) after 52 weeks.Compared with a traditional HC weight loss diet, consumption of an LC high protein diet does not adversely affect clinical markers of renal function in obese adults with T2DM and no preexisting kidney disease.


Multi-parameter Sub-Hertz Analysis of Viscoelasticity With a Quality Metric for Differentiation of Breast Masses.
We applied sub-Hertz analysis of viscoelasticity (SAVE) to differentiate breast masses in pre-biopsy patients. Tissue response during external ramp-and-hold stress was ultrasonically detected. Displacements were used to acquire tissue viscoelastic parameters. The fast instantaneous response and slow creep-like deformations were modeled as the response of a linear standard solid from which viscoelastic parameters were estimated. These parameters were used in a multi-variable classification framework to differentiate malignant from benign masses identified by pathology. When employing all viscoelasticity parameters, SAVE resulted in 71.43% accuracy in differentiating lesions. When combined with ultrasound features and lesion size, accuracy was 82.24%. Adding a quality metric based on uniaxial motion increased the accuracy to 81.25%. When all three were combined with SAVE, accuracy was 91.3%. These results confirm the utility of SAVE as a robust ultrasound-based diagnostic tool for non-invasive differentiation of breast masses when used as stand-alone biomarkers or in conjunction with ultrasonic features.