Scoring of MYC protein expression in diffuse large B-cell lymphomas: concordance rate among hematopathologists.
Recent studies have shown that immunohistochemical evaluation of MYC protein expression in diffuse large B-cell lymphoma is a useful prognostic tool with high concordance rate among pathologists. Concordance in these studies was assessed among few pathologists from one institution by scoring tissue microarrays. In daily practice, MYC evaluation is performed on entire tumor sections by a diverse group of pathologists. In our study, nine hematopathologists from two institutions scored whole-tissue sections of two sets of cases. The training set included 13 cases of diffuse large B-cell lymphoma and 4 cases of Burkitt lymphoma. The validation set included 18 cases of diffuse large B-cell lymphoma and 1 case of Burkitt lymphoma. MYC positivity was defined as ≥40% of tumor cells demonstrating nuclear staining similar to prior studies. The mean score for each case was used to determine MYC status with discrepant cases defined as having any score causing a different MYC status designation. Discrepant cases from the training set were characterized by staining heterogeneity, extensive necrosis or crush artifact and had mean scores within 15 percentage points of 40%. Cases from the validation set that demonstrated any of these features were scored twice on two different days. Overall concordance was moderate (Kappa score: 0.68, P-value<0.001) with no significant change between the two sets (Kappa scores: 0.69 vs 0.67). Thirty-nine percent of cases were discrepant. The findings indicate that a significant number of diffuse large B-cell lymphomas are inherently difficult to score due to staining heterogeneity. The effect of heterogeneity can be under-represented when concordance is measured among few pathologists scoring tissue microarrays. Careful scoring strategy in our study failed to improve concordance. In the absence of specific instructions on how to deal with heterogeneity, caution is advised when evaluating MYC expression in diffuse large B-cell lymphoma.


Anosognosia and procedural learning in Alzheimer's disease.
Awareness of cognitive deficits may rely on the implicit learning of intellectual limitations, and anosognosia in Alzheimer's disease (AD) may result from deficits in implicit learning. To examine this hypothesis, a consecutive series of 55 patients with probable AD were divided into groups with mild (n = 13), severe (n = 12), or no anosognosia (n = 30) and were assessed with a neuropsychological battery that included tests of declarative and procedural learning. Whereas there were no significant between-group differences in tests of declarative learning (the Buschke Selective Reminding Test and the Benton Visual Retention Test), patients with severe anosognosia showed a significantly worse performance on procedural learning (as measured with the Maze Learning Test) and a test assessing set shifting abilities (the Wisconsin Card Sorting Test) than AD patients without anosognosia. The authors' results suggest that deficits in procedural learning and anosognosia in AD may result from dysfunction in habit-learning systems.


Headache as a symptom of ominous disease. What are the warning signals?
Headache can be an invaluable premonitory signal of imminent subarachnoid hemorrhage and cerebral infarction and can herald the onset of ominous and sometimes elusive disorders (arterial dissection, encephalitis, systemic and central vasculitides, and cerebral venous thrombosis) which have the potential for neurologic catastrophe and are often not obvious on routine CT brain imaging. Only rarely does serious underlying disease give rise to a headache that exactly mimics a migraine or tension headache. Inevitably, there are atypical features or warning signals. A limited number of serious causes for headache which may be "CT-negative" should be considered in patients with "red flag" manifestations, such as seizures and cognitive changes. These should prompt further investigation with MRI and/or lumbar puncture.


SHARP ENTRYWISE PERTURBATION BOUNDS FOR MARKOV CHAINS.
For many Markov chains of practical interest, the invariant distribution is extremely sensitive to perturbations of some entries of the transition matrix, but insensitive to others; we give an example of such a chain, motivated by a problem in computational statistical physics. We have derived perturbation bounds on the relative error of the invariant distribution that reveal these variations in sensitivity. Our bounds are sharp, we do not impose any structural assumptions on the transition matrix or on the perturbation, and computing the bounds has the same complexity as computing the invariant distribution or computing other bounds in the literature. Moreover, our bounds have a simple interpretation in terms of hitting times, which can be used to draw intuitive but rigorous conclusions about the sensitivity of a chain to various types of perturbations.


Cytochrome P450 2B isoenzymes are responsible for the pulmonary bioactivation and toxicity of butylated hydroxytoluene, O,O,S-trimethylphosphorothioate and methylcyclopentadienyl manganese tricarbonyl.
O,O,S-Trimethylphosphorothioate and methylcyclopentadienyl manganese tricarbonyl damage the type I pneumocytes of the alveolar epithelium in rats. Butylated hydroxytoluene causes similar damage in mice. The toxicity of these compounds is dependent on their bioactivation by the cytochrome P-450 (CYP) system. A range of compounds, that modifies the activity of specific CYP isoenzymes, has been used to establish those particular isoenzymes involved in bioactivation. Pulmonary toxicity was assessed by measurement of lung weight and changes in the activity of gamma-glutamyltranspeptidase and alkaline phosphatase in bronchoalveolar lavage fluid. O,O,S-Trimethylphosphorodithioate, bromophos, p-xylene and 2,4-dichloro-(6-phenyl-phenoxy)ethylamine all inhibited the dealkylation of pentoxyresorufin, an indicator of CYP2B1 activity, and also prevented pulmonary toxicity. There was a significant negative correlation between the level of pulmonary pentoxyresorufin dealkylation after pretreatment with O,O,S-trimethylphosphorodithioate and the severity of lung injury. This pretreatment also reduced the toxicity of butylated hydroxytoluene by a factor of 20 and methylcyclopentadienyl manganese tricarbonyl by a factor of 10. Modification of the activity of CYP1A1, CYP2E1 and CYP4B1 did not alter the toxicity of these compounds. These results indicate that pulmonary CYP2B1 is responsible for the bioactivation and toxicity of O,O,S-trimethylphosphorothioate and methylcyclopentadienyl manganese tricarbonyl in rats and the orthologous 2B isoenzyme in mice activates butylated hydroxytoluene.


Adaptive Fuzzy Output-Feedback Decentralized Control for Fractional-Order Nonlinear Large-Scale Systems.
This article studies the adaptive fuzzy output-feedback decentralized control problem for the fractional-order nonlinear large-scale systems. Since the considered strict-feedback systems contain unknown nonlinear functions and unmeasurable states, the fuzzy-logic systems (FLSs) are used to model unknown fractional-order subsystems, and a fuzzy decentralized state observer is established to obtain the unavailable states. By introducing the dynamic surface control (DSC) design technique into the adaptive backstepping control algorithm and constructing the fractional-order Lyapunov functions, an adaptive fuzzy output-feedback decentralized control scheme is developed. It is proved that the decentralized controlled system is stable and that the tracking and observer errors are able to converge to a neighborhood of zero. A simulation example is given to confirm the validity of the proposed control scheme.


Mother's age and daughter's fecundity. An epidemiological analysis of late 19th to early 20th century family reconstitutions.
At both ends of the female reproductive span, the risk of reproductive problems is increased. We hypothesize that this is partly explained by inadequate maturation of oocytes ('pre-ovulatory overripeness'). As this phenomenon has been shown to lead to gonadal anomalies in the offspring of animals, we tested the prediction that daughters of older and very young mothers more often suffer reproductive problems due to ovarian maldevelopment. We analysed family reconstitutions of 1907 women born in Rotterdam, the Netherlands, between 1873 and 1902. We defined several measures of fecundity based on numbers, birth rates and fates of offspring. We made use of general estimating equations (GEE), a statistical technique that allowed simultaneous analysis of different births per woman while controlling for various time-dependent or time-independent co-variables. The results indicated an increased risk of childlessness (adjusted odds ratio (aOR = 2.6, 95% CI : 1.1-7.4), stillbirth (aOR = 2.5, 95% CI : 1.1-5.6) and multiple birth (aOR = 2.1, 95% CI : 0.8-5.4) for daughters of mothers of >or=40 years as compared to daughters born to mothers of intermediate age (24-30 years). Daughters of mothers of <or=20 years, on the other hand, did not appear to have reduced fecundity. The results point to a decreased fecundity of daughters of older mothers, but not of daughters of younger mothers. The inconsistency of the results with respect to the oocytal-maturation hypothesis points to the action of other causal or non-causal mechanisms.


Point-of-Care Lung Ultrasound in Adults: Image Acquisition.
Consultative ultrasound performed by radiologists has traditionally not been used for imaging the lungs, as the lungs' air-filled nature normally prevents direct visualization of the lung parenchyma. When showing the lung parenchyma, ultrasound typically generates a number of non-anatomic artifacts. However, over the past several decades, these artifacts have been studied by diagnostic point-of-care ultrasound (POCUS) practitioners, who have identified findings that have value in narrowing the differential diagnoses of cardiopulmonary dysfunction. For instance, in patients presenting with dyspnea, lung POCUS is superior to chest radiography (CXR) for the diagnosis of pneumothorax, pulmonary edema, lung consolidations, and pleural effusions. Despite its known diagnostic value, the utilization of lung POCUS in clinical medicine remains variable, in part because training in this modality across hospitals remains inconsistent. To address this educational gap, this narrative review describes lung POCUS image acquisition in adults, including patient positioning, transducer selection, probe placement, acquisition sequence, and image optimization.


Organocatalytic C(sp3)-H Functionalization of 5-Methyl-2,3-dihydrofuran Derivatives with Trifluoropyruvates via a Sequential exo-Tautomerization/Carbonyl-Ene Process.
An organocatalytic C(sp3)-H functionalization of 5-methyl-2,3-dihydrofuran derivatives with trifluoropyruvates was achieved via a sequential exo-tautomerization/carbonyl-ene process, providing the biologically important CF3-substituted 2,3-dihydrofurans in high yields. This method featured mild metal-free conditions, good chemoselectivity, and easy scalability.


Costoclavicular Joint: An Osteological Study on Clavicles with Clinical Relevance.
Introduction The current study aims to detect the incidence of occurrence of a morphological variant of the impression for the costoclavicular ligament, that is a faceted apophysis of the clavicle which participates in the formation of an aberrant joint, the so-called costoclavicular joint. Methods A material of 208 dry clavicles, 107 of right and 101 of left side derived from an osteological collection, was examined in order to detect the likely presence of facet apophysis at the clavicular area of impression for the costoclavicular ligament. Results We observed three cases of oval-shaped faceted apophysis, thus an incidence of 1.44%, two in right clavicles and one in left clavicle. Conclusion The awareness of such a rare joint, thus the costoclavicular joint, is important for the physician, since such a joint may be mistaken for occupying space lesion, induce pain when it is osteoarthritic and decrease the costoclavicular space leading to difficulties in subclavian vein catheterization.


A brief history of FASEB and its programs and activities.
The Federation of American Societies for Experimental Biology (FASEB) was formed in 1912 to serve the needs of its four charter societies. Its growth, from these organizations with a little more than 300 members to nearly 30 societies with over 100 000 members, is a tribute to its ability to respond to the changing structure and needs of the experimental biology community. The Federation began as a loosely constructed, single-purpose organization established to facilitate the coordination of the annual meeting of its four member societies. Following World War II, the limitations of this informal structure became readily apparent, and the development of a professional staff under the leadership of Milton O. Lee ushered in the second phase of FASEB's history. Lee oversaw a period of substantial institutional growth, but when he retired in the mid-1960s the unresolved issues of governance and member autonomy loomed large. These became increasingly divisive sources of organizational friction and were not meaningfully resolved until the Williamsburg Retreat of 1989 restructured the Federation and initiated the third phase of its existence. The changes made as a result of this pivotal event gave FASEB a new raison d'etre (public affairs) and made the organization attractive to many other biomedical research societies. Membership grew rapidly in the 1990s and early years of the 21st century. This larger membership, along with changing financial relationships, present new challenges for the Federation and are precipitating another restructuring.


Pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia.
The pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia (BPH) are incompletely understood; however, the development of reliable instruments to measure symptom severity, prostatic enlargement, and bladder outlet obstruction has allowed major advances in their elucidation. The development of lower urinary tract symptoms (LUTS) in the aging male is influenced to some degree by the severity of bladder outlet obstruction and prostatic enlargement. Although the development of LUTS, bladder outlet obstruction, and BPH are age-dependent, they are not necessarily causally related; there are many other factors involved in the pathophysiology of LUTS. The clinically important parameters of disease progression in men with moderate to severe LUTS and low peak flow rates are symptom progression and the development of acute urinary retention (AUR). The risk of AUR is related to both baseline serum prostate-specific antigen level and prostate volume. In men with moderate prostate enlargement, the risk of AUR appears to be high enough to justify intervention with a 5alpha-reductase inhibitor in order to reduce this risk.


Integrity of gut mucosa during anaesthesia in major abdominal surgery.
The aim of the study was to examine a perfusion and integrity of small bowel in 60 subsequent patients during the major open abdominal surgery which lasted from 2 to 7 hours. Two samples of the intestinal mucosa were removed: at the beginning, and at the end of the surgical procedure in general anaesthesia. A mucosal injury was classified into 4 grades. pH, PCO2 and lactate level were measured in the blood samples from the arterial and mesenteric vein in one hour time intervals. The changes of intestinal mucosa were found in 31 patients (51.7%): in 19 patients (31.7%) grade 1 changes were recorded, in 10 patients (16.7%) grade 2, and in 2 patients (3.3%) grade 3. Grade 4 lesions were not recorded. There was a statistically significant correlation between grades of the mucosal damage and the surgery duration (p = 0.001). Analysis during the one hour intervals showed that there was no exact time point when the significant aggravation of the pathohistological changes in intestinal mucosa occurred. However, when patients were allocated into two subgroups with surgical procedures lasting less than 4 hours and more than 4 hours, there was a statistically significant difference in the grades of mucosal damage between subgroups (p < 0.05). More biopsies without pathohistological changes were observed in the patients whose procedure duration was < 4 hours. A significantly higher lactate concentrations in arterial and mesenteric venous blood were observed in the patients with pathohistological changes at 6 hours time point as compared to 2 hour time point in the patients without pathohistological changes (p < 0.05). During the open abdominal surgery in general anaesthesia, the length of the procedure influences the grade of the intestinal mucosa injury. Deterioration of the pathohistological findings in the intestinal mucosa correlates with high lactate blood level, suggesting that the cause of these changes may result from tissue hypoxia.


Xanthosine and xanthine. Substrate properties with purine nucleoside phosphorylases, and relevance to other enzyme systems.
Substrate properties of xanthine (Xan) and xanthosine (Xao) for purine nucleoside phosphorylases (PNP) of mammalian origin have been reported previously, but only at a single arbitrarily selected pH and with no kinetic constants. Additionally, studies have not taken into account the fact that, at physiological pH, Xao (pKa = 5.7) is a monoanion, while Xan (pKa = 7.7) is an equilibrium mixture of the neutral and monoanionic forms. Furthermore the monoanionic forms, unlike those of guanosine (Guo) and inosine (Ino), and guanine (Gua) and hypoxanthine (Hx), are still 6-oxopurines. The optimum pH for PNP from human erythrocytes and calf spleen with both Xao and Xan is in the range 5-6, whereas those with Guo and Gua, and Ino and Hx, are in the range 7-8. The pH-dependence of substrate properties of Xao and Xan points to both neutral and anionic forms as substrates, with a marked preference for the neutral species. Both neutral and anionic forms of 6-thioxanthine (pKa = 6.5 +/- 0.1), but not of 2-thioxanthine (pKa = 5.9 +/- 0.1), are weaker substrates. Phosphorolysis of Xao to Xan by calf spleen PNP at pH 5.7 levels off at 83% conversion, due to equilibrium with the reverse synthetic pathway (equilibrium constant 0.05), and not by product inhibition. Replacement of Pi by arsenate led to complete arsenolysis of Xao. Kinetic parameters are reported for the phosphorolytic and reverse synthetic pathways at several selected pH values. Phosphorolysis of 200 micro m Xao by the human enzyme at pH 5.7 is inhibited by Guo (IC50 = 10 +/- 2 micro m), Hx (IC50 = 7 +/- 1 micro m) and Gua (IC50 = 4.0 +/- 0.2 micro m). With Gua, inhibition was shown to be competitive, with Ki = 2.0 +/- 0.3 micro m. By contrast, Xao and its products of phosphorolysis (Xan and R1P), were poor inhibitors of phosphorolysis of Guo, and Xan did not inhibit the reverse reaction with Gua. Possible modes of binding of the neutral and anionic forms of Xan and Xao by mammalian PNPs are proposed. Attention is directed to the fact that the structural properties of the neutral and ionic forms of XMP, Xao and Xan are also of key importance in many other enzyme systems, such as IMP dehydrogenase, some nucleic acid polymerases, biosynthesis of caffeine and phosphoribosyltransferases.


Participation of bone marrow cells in biliary fibrosis after bile duct ligation.
Bone marrow derived cells are involved in the process of hepatic fibrosis secondary to chronic injury. However, it is not yet known how quickly this event occurs in acute fibrosis models. The purpose of this study was to determine the role of bone marrow cells in rapid fibrosis following bile duct ligation in mice using green fluorescent protein (GFP) expressing bone marrow cells. After whole body irradiation, 1 x 10(6) donor whole bone marrow cells from green fluorescent protein(+/-) mice were transplanted into C57BL/6 recipients via the tail vein. Four weeks after bone marrow transplantation, chimeric mice were subjected to common bile duct ligation, and livers of these animals were histologically examined after bile duct ligation using anti-fibroblast specific protein (FSP)-1 antibody and anti-alpha-smooth muscle actin (alpha-SMA) antibody. Periductal fibrosis consisting of fibroblast specific protein-positive cells was demonstrated histologically as early as day 7. Most of the fibrotic cells were green fluorescent protein-negative, however, a significant number of cells were green fluorescent protein-positive and some were also anti-FSP or alpha-SMA-positive. Differentiation of bone marrow derived cells into activated fibroblast and myofibroblast-like phenotypes occurs in the very early course of periductal fibrosis following bile duct ligation, suggesting a new strategy for prevention of biliary fibrosis by inhibiting migration of bone marrow cells to liver.


The Schwartz-Jampel syndrome: Case report and review of literature.
Schwartz-Jampel syndrome (SJS), first described in the United States in 1962, is a hereditary disorder characterized by facial dysmorphism and muscle stiffness. We describe the first case of a Persian 9-year-old boy with SJS and review the literature. The child had a short neck, blepharophimosis, flattened face, hypertrichosis of the eyelids, prominent eyebrows, high arched palate, low set ears, micrognathia, short stature, and skeletal deformities. He had proximal muscle hypertrophy, distal muscle wasting and generalized hyporeflexia. Bone X-ray revealed pseudofracture of humerus. Needle electromyography revealed continuous myotonic discharges at rest with no waxing and waning in all tested muscles. Based on clinical and electrodiagnostic findings, the diagnosis of SJS type 1B was made and procainamide was started which resulted in clinical improvement. The diagnosis of SJS should be suspected when a child presents with the triad of myotonia, facial dysmorphism and skeletal deformities.


Lung Tissue Delivery of Virus-Like Particles Mediated by Macrolide Antibiotics.
Macrophage cells are present in high abundance in the lung to intercept invading microorganisms that gain access through airway mucosal surfaces. Several bacterial pathogens have evolved the capacity to evade the innate immune response by establishing infections within pulmonary macrophages upon phagocytosis, leading to prolonged disease. Macrolide antibiotics such as azithromycin and clarithromycin accumulate in phagocytic cells and have been shown to preferentially distribute in tissues where populations of these cells reside. We employed this class of molecules as targeting ligands to direct virus-like particles (VLPs) to lung-resident macrophages. VLP-macrolide conjugates showed enhanced uptake into RAW 264.7 macrophage cells in culture, with azithromycin displaying the greatest effect; distinct differences were also observed for different macrocycle structures and orientations on the particle surface. Activation of macrophage cells was stimulated by particle uptake toward an intermediate activation state, in contrast to previous reports using macrolide-functionalized gold nanorods that stimulated a cytotoxic macrophage response. Attached azithromycin was also able to direct VLPs to the lungs in mice, with significant accumulation within 2 h of systemic injection. These results suggest that this new class of bioconjugate could serve as an effective platform for intracellular drug delivery in the context of pulmonary infections.


Pregnancy with Facial Cleft: 20 Years of Experience at a Single Center.
Fetal facial clefts are among the most common congenital anomalies detected prenatally. This finding may lead to termination of pregnancy in some cases. To compare a cohort of fetuses with facial clefts in which the pregnancy was terminated to the cohort of cases that were born with facial clefts. To investigate risk factors for facial clefts. We conducted a retrospective chart review of all women with prenatal and postnatal diagnosis of facial cleft that were managed in our institute. A telephone questionnaire was conducted regarding a positive family history and/or genetic predisposition for facial clefts abnormalities. The final cohort consisted of two group. One group included 54 cases of termination of pregnancy (TOP) that were performed due to cleft lip (CL) or cleft palate (CLP); 27 women answered the telephone questionnaire. The second group comprised 99 women who delivered children with facial cleft during the same period; 60 answered the questionnaire. Only seven cases were diagnosed prenatal. Among the two groups, no correlation to family history was discovered. Of note, there was one case of three consecutive fetuses with CL in one woman, without any significant genetic findings. To the best of our knowledge, this is the first study to describe an anatomical malformation posing an ethical dilemma before TOP. Primary prevention with folic acid and early sonographic detection of CL/CLP with multidisciplinary consultation should be considered.


Treatment of intrabony defects using guided tissue regeneration or enamel matrix derivative: a 3-year prospective randomized clinical study.
The aim of this randomized, controlled, prospective clinical study was to compare guided tissue regeneration (GTR) to enamel matrix derivative (EMD) for the treatment of intrabony defects in patients with chronic advanced periodontitis. Forty (39 evaluable) 3-wall intrabony defects, each with a depth > or = 4 mm measured from the crest of the bony defect, were treated in 40 subjects with advanced chronic periodontitis. Regeneration of angular bone defects was induced using non-resorbable membranes (GTR group; n = 20) or EMD (EMD group; evaluable n = 19). Clinical parameters, including probing depth (PD), clinical attachment level (CAL), gingival recession, radiographic measurement of the defect depth, plaque index, and bleeding on probing, were measured at baseline and at 12 and 36 months following surgery. Twelve months after surgery, sites treated with GTR demonstrated a mean CAL gain of 2.5 +/- 1.2 mm and a mean reduction in PD of 3.5 +/- 1.2 mm compared to baseline. The corresponding outcomes at 36 months were 2.0 +/- 1.1 mm (CAL) and 3.2 +/- 1.1 mm (PD). Sites treated with EMD demonstrated a mean CAL gain of 2.9 +/- 1.4 mm and a mean reduction in PD of 3.5 +/- 1.4 mm at 12 months, with a mean CAL gain of 2.4 +/- 1.2 mm and a mean PD reduction of 3.1 +/- 1.4 mm at 36 months. The differences in PD reduction and CAL gain were statistically significant between the groups and for each time point compared to baseline. Attachment loss was seen in both groups between the 12- and 36-month observations. Measured radiographic bone fill was 57.0% +/- 21% at 12 months and 53.7% +/- 14.3% at 36 months in the GTR group compared to 50.5% +/- 19% at 12 months and 58.8% +/- 14.9% at 36 months in the EMD group. The treatment of intrabony defects in patients with chronic advanced periodontitis using GTR or EMD led to significantly improved clinical parameters. Tests of statistical significance demonstrated better results with EMD, although the absolute differences between treatment modalities was small. Further studies with a larger number of treated defects are necessary to verify these findings.


Coupling of growth arrest and differentiation at a distinct state in the G1 phase of the cell cycle: GD.
The differentiation of most mammalian cells is preceded by growth arrest in the G1 phase of the cell cycle, but the characteristics of this state have not been established. We now report that the growth arrest that precedes the differentiation of BALB/c 3T3 T mouse proadipocytes must occur at a distinct state in G1 designated GD. GD-arrested cells are characterized by their ability to differentiate in the absence of DNA synthesis and by their unique sensitivity to the mitogenic effect of isobutylmethylxanthine. Proadipocytes induced to become G1 growth arrested at other states by culture in medium deficient in growth factor or nutrients, by contrast, are unable to differentiate in the absence of DNA synthesis and are not stimulated to proliferate by isobutylmethylxanthine even when they are exposed to differentiation-promoting medium prior to arrest. These data support the conclusion that, prior to the expression of a differentiated phenotype, proadipocytes must arrest their growth at a distinct state in the G1 phase of the cell cycle, GD. These data also provide the basis for the hypothesis that carcinogenesis is associated with defects in the coupling of growth arrest and differentiation at the GD state.


A Leadership and Managerial Competency Framework for Public Hospital Managers in Vietnam.
The aim of this paper was to develop a leadership and managerial competency framework for public hospital managers in Vietnam. This mixed-method study used a four-step approach. The first step was a position description content analysis to identify the tasks hospital managers are required to carry out. The resulting data were used to identify the leadership and managerial competency factors and items in the second step. In the third step, a workshop was organized to reach consensus about the validity of these competency factors and items. Finally, a quantitative survey was conducted across a sample of 891 hospital managers who are working in the selected hospitals in seven geographical regions in Vietnam to validate the competency scales using exploratory factor analysis (EFA) and Cronbach's alpha. The study identified a number of tasks required for public hospital managers and confirmed the competencies for implementing these tasks effectively. Four dimensions with 14 components and 81 items of leadership and managerial competencies were identified. These components exhibited 83.8% of variance and Cronbach's alpha were at good level of 0.9. These competencies are required for public hospital managers which provide guidance to the further development of the competency-based training for the current management taskforce and preparing future hospital managers.


Effect of Pathogen Virulence on Pathogenicity, Host Range, and Reproduction of Plasmodiophora brassicae, the Causal Agent of Clubroot Disease.
A series of greenhouse experiments was conducted to evaluate the effect of Plasmodiophora brassicae virulence on clubroot development and propagation of resting spores in 86 plant species from 19 botanical families. Plants were artificially inoculated with two isolates of P. brassicae, which were virulent on clubroot-resistant oilseed rape cultivar Mendel [pathotype 1; P1 (+)] or avirulent on this cultivar (P1). Clubroot severity and the number of resting spores inside the roots were assessed 35 days post inoculation. Typical clubroot symptoms were observed only in the Brassicaceae family. P1 (+)-inoculated species exhibited more severe symptoms (two- to 10-fold more severe), bigger galls (1.1- to 5.8-fold heavier), and greater numbers of resting spores than the P1-inoculated plants. Among all Brassica species, Bunias orientalis, Coronopus squamatus, and Raphanus sativus were fully resistant against both isolates, whereas Camelina sativa, Capsella bursa-pastoris, Coincya monensis, Descurainia sophia, Diplotaxis muralis, Erucastrum gallicum, Neslia paniculata, Sinapis alba, Sinapis arvensis, Sisymbrium altissimum, Sisymbrium loeselii, and Thlaspi arvense were highly susceptible. Conringia orientalis, Diplotaxis tenuifolia, Hirschfeldia incana, Iberis amara, Lepidium campestre, and N. paniculata were completely or partially resistant to P1 isolate but highly susceptible to P1 (+). These results suggest that the basis for resistance in these species may be similar to that found in some commercial cultivars, and that these species could contribute to the buildup of inoculum of virulent pathotypes. Furthermore, the pathogen DNA was detected in Alopecurus myosuroides, Phacelia tanacetifolia, Papaver rhoeas, and Pisum sativum. It can be concluded that the number and diversity of hosts for P. brassicae are greater than previously reported.


Computational fluid dynamic analysis to prevent aortic root and valve clots during left ventricular assist device support.
Aortic root and valve clots are rare but well described in patients on maximal left ventricular assist device (LVAD) support. We performed a theoretical analysis using computational fluid dynamic analyses in two dimensions to try and ascertain if inflow cannula design/orientation/placement affect aortic root flow dynamics. Two-dimensional computational fluid dynamics using easy CFD-G was performed. The effect of a curved inflow cannula, a straight cannula, and one with a hole in the outer curve was analyzed. In addition, the effect of inflow conduit angulation on the ascending aorta was studied. Computational fluid dynamic (CFD) analysis predicts that stagnant blood exists in the aortic root when little or no cardiac ejection is taking place. Coronary flow is too small to affect the root flow streamlines. A hole on the root side of a curved inflow aortic cannula increases the flow in the aortic root and may decrease the incidence of root and valve thrombosis. The angle of the inflow conduit attachment to the ascending aorta was also found to be crucial with regard to aortic root blood stasis. In addition, a baffle at the tip of the inflow cannula may prove to be beneficial. Theoretical analysis using the technique of CFD predicts that inflow cannula position and design may affect the incidence of aortic root thrombosis during LVAD support when minimal cardiac ejection is occurring.


Soft-computing base analyses of the relationship between annoyance and coping with noise and odor.
The majority of research on annoyance as an important impact of noise, odor, and other stressors on man, has regarded the person as a passive receptor. It was however recognized that this person is an active participant trying to alter a troubled person-environment relationship or to sustain a desirable one. Coping has to be incorporated. This is of particular importance in changing exposure situations. For large populations a lot of insight can be gained by looking at average effects only. To investigate changes in annoyance and effects of coping, the individual or small group has to be studied. Then it becomes imperative to recognize the inherent vagueness in perception and human behavior. Fortunately, tools have been developed over the past decades that allow doing this in a mathematically precise way. These tools are sometimes referred to by the common label: soft-computing, hence the title of this paper. This work revealed different styles of coping both by blind clustering and by (fuzzy) logical aggregation of different actions reported in a survey. The relationship between annoyance and the intensity of coping it generates was quantified after it was recognized that the possibility for coping is created by the presence of the stressor rather than the actual fact of coping. It was further proven that refinement of this relationship is possible if a person can be identified as a coper. This personal factor can be extracted from a known reaction to one stressor and be used for predicting coping intensity and style in another situation. The effect of coping on a perceived change in annoyance is quantified by a set of fuzzy linguistic rules. This closes the loop that is responsible for at least some of the dynamics of the response to a stressor. This work thus provides all essential building blocks for designing models for annoyance in changing environments.


In vitro and in vivo assays on egg white/polyvinyl alcohol/clay nanocomposite hydrogel wound dressings.
Novel nanocomposite hydrogel wound dressings on the basis of egg white and polyvinyl alcohol, as matrix, and natural Na-montmorillonite clay, as reinforcing agent, were prepared and their performances on wound healing investigated in vitro and in vivo. In vitro cytotoxicity assay revealed non-cytotoxic activity and excellent biocompatibility level of prepared nanocomposite hydrogel wound dressings. The bacterial penetration assay showed the prepared nanocomposite hydrogel wound dressings are excellent barriers against microorganisms and could protect the wound from infection during the wound healing. In vivo animal study showed that the wound healing process was considerably faster in wounds covered with nanocomposite hydrogel wound dressings compared to the conventional wound dressing, i.e. sterile gauze, due to creation of a moist environment on the wound surface and faster migration rate of the epidermal cells. The mechanical properties of healed wounds with nanocomposite hydrogel wound dressings were better than those control wounds covered with sterile gauze due to their better collagen formation ability as a result of created moist healing condition as well as the presence of egg white, as a source of proteins, in their structures.


Cytomorphological Spectrum of Head and Neck Lesions by Fine Needle Aspiration Cytology in a Tertiary Care Center.
Fine needle aspiration cytology (FNAC) is considered the first line investigation of choice for evaluating head and neck swellings as it is a quick, safe, and rapid diagnostic procedure. This is a retrospective study that included 242 cases of head and neck lesions in the Department of Pathology, Maharaja Agrasen Medical College, Agroha. FNAC was performed by aspiration and non aspiration techniques, and cytological diagnosis was given and correlated with clinical findings and investigations. The most common age group affected was 21-30 years. Male to female ratio was 1:1.49. Out of 242 cases, maximum lesions were found in lymph nodes (128 cases), followed by thyroid gland in 81 cases, salivary gland in 23 cases, and miscellaneous group in 10 cases. Maximum number of cases reported were inflammatory (55.37%), followed by benign (29.33%) and malignant (11.15%) cases. Most swellings occurring in the head and neck region are inflammatory in nature. Our study concluded that FNAC is a simple, safe, and minimal invasive technique that differentiates between neoplastic and non neoplastic lesions and avoids unnecessary surgeries.


An intake of americium oxide powder: implications for biokinetic models for americium.
A worker inhaled 241AmO2 powder. Air sampling showed low activities but a nose blow revealed 92 Bq. Results from faecal sampling and lung and whole-body monitoring indicated an intake of about 200 Bq, but urine sampling, though commencing only 1 d after intake, showed below-threshold activities (< 0.2 mBq). This conflicts with predictions based on the ICRP Publication 67 biokinetic model for americium and the ICRP Publication 66 model for the human respiratory tract, if default lung parameters are used.


Cellular changes associated with persistent hepatitis A infection in vitro.
The rate of division, morphology and ultrastructure of BSC-1 cells, persistently infected with hepatitis A virus (HAV), were compared with uninfected cells for 60 days after splitting of the cells. Both control and infected cells showed a biphasic growth pattern marked firstly by increasing cell density and high mitotic rate (exponential phase) and then high constant cell density and little mitosis (stationary phase). Immunoperoxidase studies showed that hepatitis A antigen (HAAg) appeared as cytoplasmic granules approximately one third of the way through the exponential phase in infected cells. The percentage of cells with HAAg rose until the early stationary phase when virtually all cells contained antigen. Radioimmunoassay demonstrated an increase in HAAg per cell in the stationary phase. Radioimmunofocus assay and immune electron microscopy confirmed the presence of HAV in infected cells in the stationary phase. Thin sectioning electron microscopy showed cytoplasmic annulate lamellae in infected cells of both phases but not in control cells.


A Nonsense Variant in COL6A1 in Landseer Dogs with Muscular Dystrophy.
A novel canine muscular dystrophy in Landseer dogs was observed. We had access to five affected dogs from two litters. The clinical signs started at a few weeks of age, and the severe progressive muscle weakness led to euthanasia between 5 and 15 months of age. The pedigrees of the affected dogs suggested a monogenic autosomal-recessive inheritance of the trait. Linkage and homozygosity mapping indicated two potential genome segments for the causative variant on chromosomes 10 and 31 harboring a total of 4.8 Mb of DNA or 0.2% of the canine genome. Using the Illumina sequencing technology, we obtained a whole-genome sequence from one affected Landseer. Variants were called with respect to the dog reference genome and compared with the genetic variants of 170 control dogs from other breeds. The affected Landseer dog was homozygous for a single, private nonsynonymous variant in the critical intervals, a nonsense variant in the COL6A1 gene (Chr31:39,303,964G>T; COL6A1:c.289G>T; p.E97*). Genotypes at this variant showed perfect concordance with the muscular dystrophy phenotype in all five cases and more than 1000 control dogs. Variants in the human COL6A1 gene cause Bethlem myopathy or Ullrich congenital muscular dystrophy. We therefore conclude that the identified canine COL6A1 variant is most likely causative for the observed muscular dystrophy in Landseer dogs. On the basis of the nature of the genetic variant in Landseer dogs and their severe clinical phenotype these dogs represent a model for human Ullrich congenital muscular dystrophy.


Computer-assisted reconstruction and motion analysis of the three-dimensional cell.
Even though several microscopic techniques provide three-dimensional (3D) information on fixed and living cells, the perception persists that cells are two-dimensional (2D). Cells are, in fact, 3D and their behavior, including the extension of pseudopods, includes an important 3D component. Although treating the cell as a 2D entity has proven effective in understanding how cells locomote, and in identifying defects in a variety of mutant and abnormal cells, there are cases in which 3D reconstruction and analysis are essential. Here, we describe advanced computer-assisted 3D reconstruction and motion analysis programs for both individual live, crawling cells and developing embryos. These systems (3D-DIAS, 3D-DIASemb) can be used to reconstruct and motion analyze at short time intervals the nucleus and pseudopodia as well as the entire surface of a single migrating cell, or every cell and nucleus in a developing embryo. Because all images are converted to mathematical representations, a variety of motility and dynamic morphology parameters can be computed that have proven quite valuable in the identification of mutant behaviors. We also describe examples of mutant behaviors in Dictyostelium that were revealed through 3D analysis.


Artificial feeding for severely disoriented, elderly patients.
The issue of artificial feeding for patients with dementia who refuse feeding by hand is a wrenching emotional problem that can cloud clinical judgement. It is helpful to apply an analytic approach to decision making. There are five steps: gathering a comprehensive clinical database; defining the goal of treatment; knowing the treatment options available, their burdens and potential benefits; understanding the law; and defining the moral framework in which care is being given. Such an approach can be used to formulate a plan of treatment in the best interests of incompetent elderly patients who cannot speak for themselves.


[Effects of various modes of therapy on the fatty acid spectrum in hyperlipoproteinemia].
Gas-chromatographic investigations of the fatty acid pattern of the fractions of serum triglyceride and serum cholesterol ester revealed characteristic changes under different therapeutic measures in altogether 120 patients with primary hyperlipoproteinaemia of the types IIa, IIb and IV. Already under the treatment with basal metabolic diet, more clearly by medication with clofibrin acid, in the hyperlipoproteinaemia type IV the decrease of the palmitic acid, the palmitoleic acid, the stearic acid and oleic acid and the increase of linoleic acid, linoleneic acid, arachidonic acid and eikopentaenic acid in the triglyceride fraction developed. These fatty acids showed the same behaviour under the therapy with derivatives of nicotinic acids in the cholesterol ester fraction in the hyperlipoproteinaemia of type IIa. The combined treatment of the type IIb resulted in the same tendencies, however not so pronounced, of the spectrum in the cholesterol esters as well as of the fatty acids esterified in the triglycerides.


Effects of brushing timing after erosive challenge on enamel loss in situ: White light interferometer and nanoindentation study.
This in situ study aimed to evaluate effects of waiting periods after erosive challenge before toothbrushing on enamel abrasion and nanoindentation hardness. Ten subjects wore intraoral appliances each with a set of 4 bovine enamel blocks. The enamel blocks were subjected to 2 cycles a day for 3 days as follows; intraoral exposure to form acquired pellicle and extraoral erosion followed by either 0, 3, 30 or 60 min intraoral exposure and then brushing, which was performed using an automatic brushing machine. Abrasive loss was assessed by white light interferometry. Nanoindentation was performed to calculate relative hardness. Abrasion and relative hardness were statistically analyzed by ANOVA. Abrasive loss was significantly less in groups exposed to saliva compared with 0 min (p<0.05); there was no significant difference between 30 and 60 min (p>0.05). Relative hardness was statistically higher after intraoral exposure, but no differences existed among any intraoral exposure periods (p>0.05).


Declining Colectomy Rates for Nonmalignant Colorectal Polyps in a Large, Ethnically Diverse, Community-Based Population.
Despite studies showing improved safety, efficacy, and cost-effectiveness of endoscopic resection for nonmalignant colorectal polyps, colectomy rates for nonmalignant colorectal polyps have been increasing in the United States and Europe. Given this alarming trend, we aimed to investigate whether colectomy rates for nonmalignant colorectal polyps are increasing or declining in a large, integrated, community-based healthcare system with access to advanced endoscopic resection procedures. We identified all individuals aged 50-85 years who underwent a colonoscopy between 2008 and 2018 and were diagnosed with a nonmalignant colorectal polyp(s) at the Kaiser Permanente Northern California integrated healthcare system. Among these individuals, we identified those who underwent a colectomy for nonmalignant colorectal polyps within 12 months after the colonoscopy. We calculated annual colectomy rates for nonmalignant colorectal polyps and stratified rates by age, sex, and race and ethnicity. Changes in rates over time were tested by the Cochran-Armitage test for a linear trend. Among 229,730 patients who were diagnosed with nonmalignant colorectal polyps between 2008 and 2018, 1,611 patients underwent a colectomy. Colectomy rates for nonmalignant colorectal polyps decreased significantly from 125 per 10,000 patients with nonmalignant polyps in 2008 to 12 per 10,000 patients with nonmalignant polyps in 2018 (P < 0.001 for trend). When stratified by age, sex, and race and ethnicity, colectomy rates for nonmalignant colorectal polyps also significantly declined from 2008 to 2018. In a large, ethnically diverse, community-based population in the United States, we found that colectomy rates for nonmalignant colorectal polyps declined significantly over the past decade likely because of the establishment of advanced endoscopy centers, improved care coordination, and an organized colorectal cancer screening program.


Micellization of dissymmetric cationic gemini surfactants and their interaction with dimyristoylphosphatidylcholine vesicles.
The micellization process of a series of dissymmetric cationic gemini surfactants [CmH2m+1(CH3)2N(CH2)6N(CH3)2C6H13]Br2 (designated as m-6-6 with m = 12, 14, and 16) and their interaction with dimyristoylphosphatidylcholine (DMPC) vesicles have been investigated. In the micellization process of these gemini surfactants themselves, critical micelle concentration (cmc), micelle ionization degree, and enthalpies of micellization (DeltaHmic) were determined, from which Gibbs free energies of micellization (DeltaGmic) and entropy of micellization (DeltaSmic) were derived. These properties were found to be influenced significantly by the dissymmetry in the surfactant structures. The phase diagrams for the solubilization of DMPC vesicles by the gemini surfactants were constructed from calorimetric results combining with the results of turbidity and dynamic light scattering. The effective surfactant to lipid ratios in the mixed aggregates at saturation (Resat) and solubilization (Resol) were derived. For the solubilization of DMPC vesicles, symmetric 12-6-12 is more effective than corresponding single-chain surfactant DTAB, whereas the dissymmetric m-6-6 series are more effective than symmetric 12-6-12, and 16-6-6 is the most effective. The chain length mismatch between DMPC and the gemini surfactants may be responsible for the different Re values. The transfer enthalpy per mole of surfactant within the coexistence range may be associated with the total hydrophobicity of the alkyl chains of gemini surfactants. The transfer enthalpies of surfactant from micelles to bilayers are always endothermic due to the dehydration of headgroups and the disordering of lipid acyl chain packing during the vesicle solubilization.


Context-dependent insect predation pressure on an avian ectoparasite.
Context dependence arises when ecological relationships vary with the conditions under which they are observed. Context dependence of interactions involving parasites is poorly known, even if it is key to understanding host-parasite relationships and food web dynamics. This paper investigates to which extent predation pressure on an avian ectoparasite (Carnus hemapterus) is context-dependent. Based on a predator-exclusion experiment, predation pressure on C. hemapterus pupae in the host's nest for 3 years, and its variation between habitat types are quantified. Variation in precipitation and normalized difference vegetation index (NDVI) is also explored as a likely cause of context dependency. We hypothesize that predation pressure should fluctuate with such surrogates of food availability, so that inter-annual and intra-annual differences may emerge. The number of nests with significant reduction of pupae varied widely among years ranging from 24% to 75%. However, average pupae reduction in nests where a significant reduction occurred did not vary between years. No differences in predation rates between habitat types were detected. Precipitation and NDVI varied widely between years and NDVI was consistently lower around nests on cliffs than around nests on trees and farmhouses. Parallels were found between variation in predation pressure and precipitation/NDVI at a wide scale (highest predation the driest year, and much lower the 2 rainier ones), but not at the nest scale. This paper shows clear context-dependent insect predation pressure on an ectoparasite under natural conditions, and that such interaction changes in signs rather than magnitude between years. The causes for these variations require longer-term studies and/or well-designed, large-scale experiments.


[Super selective transcatheter arterial embolization for treatment of focal nodular hyperplasia of the liver: report of 21 cases].
To evaluate the efficiency and safety of transcatheter arterial embolization (TAE) for treatment of focal nodular hyperplasia (FNH). From January 2005 to December 2010, super selective TAE was performed for 21 patients with FNH. The patients consisted of 16 men and 5 women with age range of 16 to 44 years (mean age, 28 ± 12). Liver contrast enhancement CT and ultrasonography (US) were performed in all patients, dynamic contrast enhancement MRI was performed in 17 patients. All patients underwent percutaneous needle biopsies and the diagnosis of FNH was proven histologically. The indications for TAE were patients with progressive increase in size of FNH, who were not candidates for surgical treatment, or who refused for surgery. Embolic materials used in this series included emulsion of iodized oil and bleomycin and polyvinyl alcohol particle (PVA). Follow-up examinations included the routine blood tests, liver and renal function tests, US, CT or MRI. Eighteen patients (85.7%) had a single solitary focus and 3 (14.3%) had multiple foci. The diameter of the mass varied from 3.5 cm to 9.5 cm with a mean of 5.5 cm (5.5 ± 3.0 cm). All patients presented angiographically with characteristic findings, such as feeding artery that was distributed with a spinning wheel appearance, an extensive hypervascular mass, without arterio-venous shunt or portal vein invasion. A single session of TAE was performed in all patients. Technical success of TAE was achieved in all cases. No major complications were encountered in any of our patients. All patients were regularly followed up ranging from 1 to 6 years (3.5 ± 2.0) and they were healthy without recurrence. Marked reduction in the size of the FNH without arterial blood supply was found in 16 patients, and almost complete resolution of the FNH was observed in 6 patients. TAE is a safe and effective therapy for the management of patients with FNH. TAE could control FNH very well and even could be considered as a radical treatment.


Electrically-evoked release of [3H]-histamine from the guinea-pig hypothalamus.
1 [3H]-histamine was taken up by slices of guinea-pig hypothalamus against a concentration gradient. 2 Electrical field stimulation of the superfused slices resulted in an increased efflux of radioactivity, the major part of which was shown to be associated with histamine by paper chromatography. 3 The evoked release of histamine was dependent on calcium ions in the superfusate and was increased by 56% when the frequency of stimulation was doubled from 5 to 10 Hz.


[Expression of Sema4D in patients with cerebral infarction and its clinical significance].
To explore the expression and clinical significance of Semaphorin4D (Sema4D) mRNA in peripheral blood lymphocyte, Sema4D on platelet surface, soluble Sema4D (sSema4D) in plasma in patients with cerebral infarction. Taking 299 patients with cerebral infarction as the case group while 195 healthy adults as the control group. The mRNA expression of Sema4D was detected by Real-time PCR, and Sema4D expression on platelet by flow cytometry, sSema4D by ELISA. Then, the expression of Sema4D on platelet surface and the concentration of sSema4D in plasma of the 195 selected patients following 2 weeks' treatment were tested. The expression of Sema4D mRNA significantly increased in the case group \[(2.23, 2.66)×10(4) IU/ml\] than in the control group \[(0.49, 0.53)×10(4)IU/ml\] (P < 0.01). The level of Sema4D on platelet surface in the case group (191.62 ± 46.56) significantly decreased than in the control group (303.33 ± 112.66) (P < 0.01). But the concentration of sSema4D in plasma in the case group \[(1.34 ± 0.56) µg/L\] was obviously higher than in the control group \[(0.61 ± 0.31) µg/L\] (P < 0.01). The expression of Sema4D on platelet was obviously relevant with the concentration of sSema4D in plasma in the case group with the correlation coefficient as 0.328 (P < 0.01). The expression of Sema4D on platelet obviously peaked up following 2 weeks' routine therapy in the case group, which was close to that in the control group. Meanwhile the concentration of sSema4D in plasma was downward corrected to the normal in the case group. The increased expressions and plasma levels, and reduced expressions on platelet of Sema4D in acute period, which returned to normal 2 weeks after treatment in the case group may be related to the occurrence of acute cerebral infarction, reflecting the development process of cerebral infarction.


Molecular basis for linkage of a continuous and discontinuous neutralization epitope on the structural polypeptide VP2 of poliovirus type 1.
We obtained neutralizing monoclonal antibodies against a continuous neutralization epitope on VP2 of poliovirus type 1 strain Mahoney by using a combined in vivo-in vitro immunization procedure. The antibody-binding site was mapped to amino acid residues within the peptide segment (residues 164 through 170) of VP2 by competition with synthetic peptide and sequencing of resistant mutants. Cross-neutralization of these mutants with another neutralizing monoclonal antibody revealed a linkage of the continuous epitope and a discontinuous neutralization epitope involving both loops of the double-loop structure of VP2 at the twofold axis on the surface of the virion.


Ketamine for anaesthetic induction at Caesarean section.
Fifty healthy mothers, with normal placental function, were anaesthetised with ketamine (2 mg/kg body mass) for Caesarean section. Surgery was conducted with the patient in the lateral tilt position and anaesthesia was maintained with nitrous oxide, oxygen, muscle relaxants and controlled ventilation. Eight of the 50 infants delivered were clinically depressed, judged on the basis of the modified Apgar score at 2 minutes after delivery. The average time to sustained respiration was 58, 1 minutes. Studies of maternal blood gases before induction and at delivery revealed mild respiratory alkalosis, associated with an appropriate degree of compensatory metabolic acidosis. Umbilical cord blood gas analysis showed the presence of a fetal respiratory acidosis. The average derived fetal base excess levels were similar to those obtained in a previous study with thiopentone anaesthesia, but calculated mean maternal-to-fetal pH and base excess gradients were slightly greater in the present study. Prolonged induction-to-delivery intervals were associated with an increase in maternal metabolic and fetal respiratory acidosis. Slow delivery of the infant after invasion of the uterus magnified the degree of fetal metabolic acidosis, and widened the maternal-to-fetal acid-base gradients. Convincing evidence of maternal awareness during surgery was not obtained in this study. Five patients had hallucinations in the immediate postanaesthetic period. Unpleasant dreams were reported by 10% of patients. Delirium on emergence from anesthesia was not encountered. In this study, ketamine appeared to maintain fetoplacental exchange adequately, but may have been responsible for some degree of drug-induced neonatal depression. It is suggested that ketamine should be re-evaluated, using a lower dosage schedule, for Caesarean section.


310 nm irradiation of atmospherically relevant concentrated aqueous nitrate solutions: nitrite production and quantum yields.
The heterogeneous processing of atmospheric aerosols by reaction with nitrogen oxides results in the formation of particulate and adsorbed nitrates. The water content of these hygroscopic nitrate aerosols and consequently the nitrate ion concentration depend on relative humidity, which can impact the physicochemical properties of these aerosols. This report focuses on the 310 nm photolysis of aqueous sodium and calcium nitrate solutions at pH 4 over a wide concentration range of nitrate ion concentrations representative of atmospheric aerosols. In particular, the quantum yield (phi) of nitrite formation was measured and found to significantly decrease at high concentrations of nitrate for Ca(NO(3))(2). In particular, phi for Ca(NO(3))(2) was found to have a maximum value of (7.8 +/- 0.1) x 10(-3) for nitrate ion solution concentrations near one molal, with the smallest quantum yield for the highest concentration solution above 14 m nitrate ion, phi = (2.3 +/- 2.0) x 10(-4). The effect of the addition of the radical scavenger, formate, on the 310 nm photolysis of these solutions was also investigated and found to increase phi by a factor of 2 or more for both sodium and calcium nitrate solutions. In the presence of formate, Ca(NO(3))(2) solutions again showed a significant decrease in phi with increasing NO(3)(-) concentration: phi = (1.4 +/- 0.1) x 10(-2) at (1.0 +/- 0.1) x 10(-2) m NO(3)(-) compared to phi = (4.2 +/- 0.3) x 10(-3) at 14.9 +/- 0.1 m NO(3)(-). This decrease in phi was not observed in NaNO(3) solutions. The change in electronic structure, as evident by the more pronounced shift of the n-pi* absorption band away from actinic wavelengths with increasing concentration for Ca(NO(3))(2) compared to NaNO(3), is most likely the origin of the greater decrease in phi for Ca(NO(3))(2) compared to NaNO(3) at elevated NO(3)(-) concentrations. The role of nitrate photochemistry in atmospheric aerosols and the atmospheric implications of these concentration dependent quantum yields are discussed.


Ectopic Pelvic Kidney Mimicking Sacral Metastasis on Post-Therapy Iodine-131 Scan of a Thyroid Cancer Patient.
A 25-year-old woman had total thyroidectomy and iodine-131 ablation therapy for papillary thyroid carcinoma. Whole body imaging on the 7th day of therapeutic activity demonstrated radioiodine uptake in the remnant tissue and intense heterogeneous uptake at the sacral region prominently in the posterior image. Initial interpretation was suspicious for sacral metastasis. Technetium-99m-methylene diphosphonate bone scan demonstrated normal bone uptake and the absence of left kidney. On blood-pool phase of bone scan, the absence of left renal activity and an extra area of uptake in the sacral region suggestive of pelvic kidney were noticed. Magnetic resonance imaging scan confirmed the ectopic pelvic kidney overlying the sacrum.


Ascending aortic aneurysms. Review of 100 consecutive cases.
Aneurysms of the ascending aorta, if undiagnosed or untreated, may result in left ventricular failure from aortic valvular insufficiency. Aortic rupture, dissection, or compression of adjacent vital structures may also occur. The application of refined cardiopulmonary bypass devices, prosthetic heart valves, and synthetic grafts now allows successful surgical management of this disorder. This report presents our current diagnostic methods, surgical techniques, and the early and late results of 100 consecutive patients undergoing surgical treatment of aneurysms of the ascending aorta. There were 72 males and 28 females, ranging in age from 25 to 72 (ave 51.2) years. All patients had angiographic studies to demonstrate precisely the location of the aneurysm and the presence or absence of aortic valvular insufficiency. Sixty-three patients required concomitant aortic valve replacement, and the remaining 37 patients had only aneurysm resection and replacement. Pathological studies revealed 69 aneurysms were atherosclerotic, 22 were secondary to cystic medial necrosis, with the remaining 9 considered to be possibly leutic in origin. Despite the magnitude of the surgery and the advanced ages of some of these patients, the overall operative and hospital mortality rates were 4% and 9%. Survival rates by actuarial representation in 82 patients at 2, 4, 6, and 8 years were 82.9%, 78%, 70%, and 69.5%, respectively.


Renal Function Recovery with Total Artificial Heart Support.
Heart failure patients requiring total artificial heart (TAH) support often have concomitant renal insufficiency (RI). We sought to quantify renal function recovery in patients supported with TAH at our institution. Renal function data at 30, 90, and 180 days after TAH implantation were analyzed for patients with RI, defined as hemodialysis supported or an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m. Between January 2008 and December 2013, 20 of the 46 (43.5%) TAH recipients (age 51 ± 9 years, 85% men) had RI, mean preoperative eGFR of 48 ± 7 ml/min/1.73 m. Renal function recovery was noted at each follow-up interval: increment in eGFR (ml/min/1.73 m) at 30, 90, and 180 days was 21 ± 35 (p = 0.1), 16.5 ± 18 (p = 0.05), and 10 ± 9 (p = 0.1), respectively. Six patients (30%) required preoperative dialysis. Of these, four recovered renal function, one remained on dialysis, and one died. Six patients (30%) required new-onset dialysis. Of these, three recovered renal function and three died. Overall, 75% (15 of 20) of patients' renal function improved with TAH support. Total artificial heart support improved renal function in 75% of patients with pre-existing significant RI, including those who required preoperative dialysis.


Robust Mutual Synchronization in Long Spin Hall Nano-oscillator Chains.
Mutual synchronization of N serially connected spintronic nano-oscillators boosts their coherence by N and peak power by N2. Increasing the number of synchronized nano-oscillators in chains holds significance for improved signal quality and emerging applications such as oscillator based unconventional computing. We successfully fabricate spin Hall nano-oscillator chains with up to 50 serially connected nanoconstrictions using W/NiFe, W/CoFeB/MgO, and NiFe/Pt stacks. Our experiments demonstrate robust and complete mutual synchronization of 21 nanoconstrictions at an operating frequency of 10 GHz, achieving line widths <134 kHz and quality factors >79,000. As the number of mutually synchronized oscillators increases, we observe a quadratic increase in peak power, resulting in 400-fold higher peak power in long chains compared to individual nanoconstrictions. While chains longer than 21 nanoconstrictions also achieve complete mutual synchronization, it is less robust, and their signal quality does not improve significantly, as they tend to break into partially synchronized states.


Office management of benign paroxysmal positional vertigo with Epley's maneuver.
The underlying cause of benign paroxysmal positional vertigo is free floating endolymph particles (otoconia displaced from the otolithic membrane of the utricle) in the posterior semicircular canal. Particle repositioning techniques are one of the effective method of treatment. The purpose of the study was to determine the effectiveness of Epley's maneuver against expectant treatment and to find out if this treatment should be used more frequently than watchful waiting for the treatment of BPPV. This study was carried out at outpatient clinic, departments of ENT, Combined Military hospital Rawalpindi and PNS Shifa hospital Karachi over a three years period from Jan, 2002 to Jan, 2005. Based upon history and Dix-hallpike testing 44 patients diagnosed as benign paroxysmal positional vertigo were collected by convenient sampling from these hospital's outpatient departments and divided by non probability convenience into two groups of 22 each. The control group (group A) was given placebo and the test group (group B) received single treatment by Epley's maneuver in the OPD. The results were analyzed at the end of one and two weeks by history taking and Dix-hallpike testing. Computer software SPSS version 10 was used. At the end of week one 14 (63.63%) patients of group B were symptom free and 2 (9.1%) patients was much better as compared to the control group where only 1 (4.5%) patient reported as symptom free and another 5 (22.7%) reported as much better. At the end of second week out of those treated by Epley's maneuver 16 (72.7%) reported as symptom free and another 2 (9.1%) as much better whereas 4 (18.2%) patients reported no improvement at all. In the control group only 4 (18.2%) patients reported as symptom free, 3 (13.6%) as much better, 6 (27.3%) as better and 9 (40.9%) reported no change in the symptoms. Chi square test was applied and the value of p came out to be 0.001 and 0.002 at week one and week two respectively. It was concluded that Epley's maneuver is a much better form of management for benign paroxysmal positional vertigo.


Interleukin-6 and some acute phase proteins plasma activity in drug-induced maculopapular eruptions.
The evaluation of inflammatory response in drug-induced maculopapular eruption was the aim of the study. Plasma concentrations of interleukin-6 (IL-6), C-reactive protein (CRP) and alpha-2 macroglobulin (alpha-2 MG) were measured in 40 patients with maculopapular eruptions using the immunoenzymatic ELISA method in acute stage of disease and after clearing of skin lesions due to effective therapy. In the acute stage of the disease mean plasma levels of the examined proteins were highly significantly elevated (p < 0.001) in comparison with healthy control. Regression of the clinical symptoms was connected with the deep decrease of protein concentrations in the peripheral blood. After treatment the plasma levels of IL-6 and alpha-2 MG were lowered towards the control values (p > 0.05), but CRP despite its deep decrease was still highly significantly elevated (p < 0.001) in comparison with control. The results of this study indicate that in drug-induced maculopapular eruptions the acute phase response can be initiated and that the observed increased activity of the examined proteins lasts longer than the clinical symptoms of the disease.


New benzothiophene derivatives as dual COX-1/2 and 5-LOX inhibitors: synthesis, biological evaluation and docking study.
Simultaneous inhibition of 5-LOX/COX may enhance anti-inflammatory effects and reduce side effects. Hence, synthesis of novel dual inhibitors of 5-LOX/COX is an important strategy for treatment of inflammation. Results/methodology: The target compounds were designed to hybridize benzothiophene scaffold or its bioisostere benzofuran with various anti-inflammatory pharmacophore hetercycles through different atoms spacers. Compounds 4a, 4c, 4d, 5b, 7a, showed significant in vitro LOX inhibitory activity higher than that of meclofenamate sodium. Compounds 4b, 4e, 4f, 5a exhibited significant in vitro COX-2 inhibition higher than celecoxib and in vitro LOX inhibitory activity twice that of reference. These compounds elicited significant in vivo anti-inflammatory activities higher than celecoxib in formalin-induced paw edema test. Compound 4e exhibited gastrointestinal safety profile as celecoxib. The results were also consistent with the docking studies. Compound 4e could be considered as structural lead for the development of a new class of anti-inflammatory agents with better safety profile.


Inhibitory effect of electroacupuncture (EA) on the pressor response induced by exercise stress.
We examined the effect of EA on the exercise stress-induced pressor response in healthy adult subjects of both sexes. Each subject was subjected to a bicycle exercise test using a ramp protocol once/week for three or four weeks. Subjects were asked to perform the following tests in random order: 1) a baseline exercise test without EA and 2) exercise after acupuncture at P 5-6, LI 4-L 7 and/or G 37-39 acupoints. Brachial systolic (SBP), diastolic (DBP), and mean blood pressures (MBP), heart rate (HR) and the rate-pressure product (RPP, systolic BP x HR/100) were measured every three min, while a 12 lead ECG was monitored continuously. We observed increases in MBP, SBP, HR and RPP in all 17 subjects during exercise. In 12 of the 17 subjects (71 %), EA for 30 min before exercise, either at Jianshi-Neiguan acupoints (P 5-6) or Hegu-Lique acupoints (LI 4-L 7), led to an increase in maximal workload, and reduced peak SBP, MBP and RPP responses to exercise; EA did not alter DBP or HR responses in these subjects. EA at control acupoints (Guangming-Xuanzhong acupoints, G 37-39) in five subjects did not alter the hemodynamic responses. Seven additional subjects were enrolled to study the effect of EA during a bicycle exercise test using a constant workload. The results were similar, in five of the seven subjects SBP, MBP and RPP after exercise were attenuated significantly by EA at P 5-6. We conclude that EA at specific acupoints improves exercise capacity and reduces the hemodynamic responses in approximately 70% of normal subjects.


Malformation of immature starfish oocytes by theonellapeptolide Ie, a Tridecapeptide lactone from a marine sponge Petrosia species, through disturbance of cortical F-actin distribution.
Theonellapeptolide Ie (Tp), an oligopeptide lactone isolated from a marine sponge, Petrosia sp., was shown to induce an unprecedented morphological change in the immature oocytes of the starfish Asterina pectinifera. The cortical F-actin was disturbed and assembled to form dots and rings, as evidenced by staining with rhodamine-conjugated phalloidin. The oocyte eventually became malformed. When Tp was added to an immature oocyte which had been pretreated with cytochalasin B or D, inhibitors of actin polymerization, no malformation was observed. When Tp was added to an oocyte which had been induced to mature by 1-methyladenine (1-MeAde), a maturation-inducing substance in starfishes, no morphological changes were observed in the maturing oocytes which reached the first meiotic prometaphase 40 min after the start of 1-MeAde treatment. This is the first description of a chemical that induces aberrant redistribution of F-actin-based cytoskeleton in an animal oocyte which is arrested at the first meiotic prophase.


Calcifications in the abdominal aorta predict fractures in men: MINOS study.
In a cohort of 781 men >or=50 yr of age followed up for 10 yr, extended calcifications in the abdominal aorta were associated with a 2- to 3-fold increase in the risk of osteoporotic fractures regardless of BMD and falls. Cardiovascular disease and osteoporotic fractures are public health problems that frequently coexist. We assessed the relation of the severity of aortic calcifications with BMD and the risk of fracture in 781 men >or=50 yr of age. During a 10-year follow-up, 66 men sustained incident clinical fractures. Calcifications in the abdominal aorta expressed as an aortic calcification score (ACS) were assessed by a semiquantitative method. BMD was measured at the lumbar spine, hip, whole body, and distal forearm. ACS > 2 was associated with a 2-fold increase in the mortality risk after adjustment for age, weight, smoking, comorbidity, and medications. After adjustment for age, body mass index (BMI), smoking, and comorbidity, men in the highest quartile of ACS (>6) had lower BMD of distal forearm, ultradistal radius, and whole body than men in the lower quartiles. Log-transformed ACS predicted fractures when adjusted for age, BMI, age by BMI interaction, prevalent fractures, BMD, and history of two or more falls (e.g., hip BMD; OR = 1.44; p < 0.02). ACS, BMD at all the skeletal sites, and history of two or more falls were independent predictors of fracture. Men with ACS > 6 had a 2- to 3-fold increased risk of fracture after adjustment for confounding variables (OR = 2.54-3.04; p < 0.005-0.001 according to the site). This long-term prospective study showed that elevated ACS (>6) is a robust and independent risk factor for incident fracture in older men regardless of age, BMI, BMD, prevalent fractures, history of two or more falls, comorbidities, and medications.


Risk Scoring Systems for Preterm Birth and Their Performance: A Systematic Review.
Introduction: Nowadays, the risk stratification of preterm birth (PTB) and its prediction remain a challenge. Many risk factors associated with PTB have been identified, and risk scoring systems (RSSs) have been developed to face this challenge. The objectives of this systematic review were to identify RSSs for PTB, the variables they consist of, and their performance. Materials and methods: Two databases were searched, and two authors independently performed the screening and eligibility phases. Records studying an RSS, based on specified variables, with an evaluation of the predictive value for PTB, were considered eligible. Reference lists of eligible studies and review articles were also searched. Data from the included studies were extracted. Results: A total of 56 studies were included in this review. The most frequently incorporated variables in the RSS included in this review were maternal age, weight, history of smoking, history of previous PTB, and cervical length. The performance measures varied widely among the studies, with sensitivity ranging between 4.2% and 92.0% and area under the curve (AUC) between 0.59 and 0.95. Conclusions: Despite the recent technological and scientifical evolution with a better understanding of variables related to PTB and the definition of new ultrasonographic parameters and biomarkers associated with PTB, the RSS's ability to predict PTB remains poor in most situations, thus compromising the integration of a single RSS in clinical practice. The development of new RSSs, the identification of new variables associated with PTB, and the elaboration of a large reference dataset might be a step forward to tackle the problem of PTB.


Oxidation behavior of P3HT layers on bare and TiO2-covered ZnO ripple structures evaluated by photoelectron spectroscopy.
P3HT layers with a thickness of ∼5 nm were deposited on bare and TiO2-covered ZnO ripple structures. The ZnO ripples were prepared wet-chemically and a TiO2 layer with a thickness less than 5 nm was prepared by atomic layer deposition. Under humid air and visible light illumination, the oxidation behaviors of P3HT on these surfaces were studied using photoelectron spectroscopy. It was found that P3HT on TiO2/ZnO oxidizes more easily than that on bare ZnO ripples. Using a model substrate of a flat ZnO surface in combination with angle-resolved photoelectron spectroscopy, we found that oxidation of P3HT occurs at the surface of the topmost layer of P3HT, not at the P3HT/oxide interfaces, even though P3HT oxidation is strongly influenced by the interface structure. It is suggested that the lifetime of electron-hole pairs can be strongly influenced by the interface structure, which can also affect the oxidation behavior of P3HT.


A guide to recognizing maxillary sinus pathology and for deciding on further preoperative assessment prior to maxillary sinus augmentation.
Dentists contemplating sinus augmentation frequently take a cone beam computed tomography (CBCT) scan as part of the work-up. Maxillary sinus pathology is common, and such dentists will be faced with pathologic sinus findings. Not all sinus pathology needs to be treated. The purpose of this article is twofold: to describe the most common sinus findings as seen on a CBCT scan and a way to recognize them, as well as to provide an algorithm for decision making on when further evaluation of the sinus is necessary.


Impact of the COVID-19 pandemic on exercise habits and overweight status in Japan: A nation-wide panel survey.
A catastrophic disaster may cause distant health impacts like immobility and obesity. The aim of this research was to analyse the association of the COVID-19 pandemic and lifestyle factors -exercise habit and overweight status in the Japanese population. Nation-wide online questionnaires were conducted five times from October 2020 to October 2021. The changes in exercise habit, body mass index (BMI) and overweight status (BMI >25kg/m2) were compared between the first questionnaire and a questionnaire conducted a year later. Risk factors for losing exercise habit or becoming overweight were analysed using multiple regression. Data were obtained from 16,642 participants. In the early phase of the pandemic, people with high income and elderly females showed a higher risk for decreased exercise days. The proportion of overweight status increased from 22.2% to 26.6% in males and from 9.3% to 10.8% in females. Middle-aged males, elderly females, and males who experienced SARS-CoV-2 infection were at higher risk of becoming overweight. Our findings suggest that risks for immobility and overweight are homogeneous. Continuous intervention for elderly females and long-term intervention for males infected with SARS-CoV-2 might be especially needed. As most disasters can cause similar social transformation, research and evaluation of immobility and obesity should address future disaster preparation/mitigation plans.


Pregnancy rates following timed embryo transfer with fresh or vitrified in vitro produced embryos in lactating dairy cows under heat stress conditions.
Timed embryo transfer (TET) using in vitro produced (IVP) embryos without estrus detection can be used to reduce adverse effects of heat stress on fertility. One limitation is the poor survival of IVP embryos after cryopreservation. Objectives of this study were to confirm beneficial effects of TET on pregnancy rate during heat stress as compared to timed artificial insemination (TAI), and to determine if cryopreservation by vitrification could improve survival of IVP embryos transferred to dairy cattle under heat stress conditions. For vitrified embryos (TET-V), a three-step pre-equilibration procedure was used to vitrify excellent and good quality Day 7 IVP Holstein blastocysts. For fresh IVP embryos (TET-F), Holstein oocytes were matured and fertilized; resultant embryos were cultured in modified KSOM for 7 days using the same method as for production of vitrified embryos. Excellent and good quality blastocysts on Day 7 were transported to the cooperating dairy in a portable incubator. Nonpregnant, lactating Holsteins (n = 155) were treated with GnRH (100 microg, i.m., Day 0), followed 7 days later by prostaglandin F2alpha (PGF2alpha, 25 mg, i.m.) and GnRH (100 microg) on Day 9. Cows in the TAI treatment (n = 68) were inseminated the next day (Day 10) with semen from a single bull that also was used to produce embryos. Cows in the other treatments (n = 33 for TET-F; n = 54 for TET-V) received an embryo on Day 17 (i.e. Day 7 after anticipated ovulation and Day 8 after second GnRH treatment). The proportion of cows that responded to synchronization based on plasma progesterone concentrations on Day 10 and Day 17 was 67.7%. Pregnancy rate for all cows on Day 45 was higher (P < 0.05) in the TET-F treatment than for the TAI and TET-V treatments (19.0 +/- 5.0,6.2 +/- 3.6, and 6.5 +/- 4.1%). For cows responding to synchronization, pregnancy rate was also higher (P < 0.05) for TET-F than for other treatments (26.7 +/- 6.4, 5.0 +/- 4.3, and 7.4 +/- 4.7%). In the TET-F treatment group, cows producing more milk had lower (P < 0.05) pregnancy rates than cows producing less milk. In conclusion, ET of fresh IVP embryos can improve pregnancy rate under heat stress conditions, but pregnancy rate following transfer of vitrified embryos was no better than that following TAI.


Central retinal artery occlusion in a 30-year-old woman taking tranexamic acid.
We present a case of a 30-year-old woman who suffered a central retinal artery occlusion while taking tranexamic acid. She had no vascular risk factors and was placed on the drug for treatment of menorrhagia. After 1 month of taking the drug, she suffered a central retinal artery occlusion in her left eye. Tranexamic acid was discontinued to prevent vision loss in the following eye. She remains with no perception of light vision in the affected eye.


[Androgen regulates penile erection at the peripheral level].
Androgen has been claimed for so long as a pivotal hormone in regulating male sexual function, acting both at the central and peripheral level. We believe that androgen is indeed the main synchronizer of sexual activity regulating libido and enzymes as nitric oxide synthase (NOS) and phosphodiesterase type 5 ( PDE5) , which are crucial for the erectile process. The main action of androgen is to timely adjust the erectile process as a function manifestation of sexual desire, therefore finalizing erection to sex.


ARID1A gene knockdown promotes neuroblastoma migration and invasion.
Neuroblastoma is the most common extracranial solid tumor in childhood which often acquires drug resistance and becomes aggressive phenotypes. The high-risk patients suffer from high mortality due to the limitation of the treatment strategies. ARID1A (AT-rich interactive domain-containing protein 1A), a subunit of SWI/SNF complexes, is considered as a tumor suppressor in many cancers. The aim of the present study was to investigate the effect of ARID1A on migration and invasion in neuroblastoma cells. The shRNA targeting ARID1A was designed and delivered into SK-N-SH cells to knock down ARID1A expression. Knockdown of ARID1A by shRNA significantly increased the viability and invasion ability, and caused G1 arrest inhibition and DNA synthesis increase in SK-N-SH cells. Moreover, Knockdown of ARID1A increased the activity and expression of matrix metalloproteinase (MMP)-2 and -9 in SK-N-SH cells. Furthermore, ARID1A knockdown caused diminished expression of E-cadherin, enhanced expression of N-cadherin and β-catenin nuclear translocation in SK-N-SH cells. These results suggest that loss of ARID1A may associate with the promotion of invasion and metastasis of neuroblastoma. Our findings indicate ARID1A is a tumor suppressor in neuroblastoma.


The Impact of Bariatric Surgery on Type 2 Diabetes Mellitus and the Management of Hypoglycemic Events.
Recent studies discussed the benefit of bariatric surgery on obese patients diagnosed with type 2 diabetes mellitus (T2DM). Several factors play an essential role in predicting the impact of bariatric surgery on T2DM, such as ABCD score (age, BMI, C-peptide, and duration of the disease), HbA1c, and fasting blood glucose, incretins [glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP)]. DiaRem score known to include factors such as age, HbA1c, medication, and insulin usage used to predict the remission of T2DM, but it has some limitations. An extensive literature search was conducted on PubMed and Google Scholar using keywords such as gastric bypass, T2DM, bariatric surgery, GLP-1, GIP, and post bariatric hypoglycemia. Restrictive-malabsorptive procedures are most effective in treating T2DM patients based on changes induced in appetite through regulation of gastrointestinal hormones, with decreased hunger and increased satiation. We provide a review of bariatric surgery influence on T2DM and management of post-intervention hypoglycemic events. Post-bariatric surgery hypoglycemia is a serious complication especially when patients develop life-threatening neuroglycopenia with loss of consciousness and seizure. The avoidance of this adverse event may be achieved by strict dietary modification including a restriction on carbohydrates as well as foods with high glycemic index. Further research will provide more information on post-bariatric surgery hyperinsulinemic hypoglycemia pathophysiology and management.


Ki67 antigen expression correlates with tumor progression and HLA-DR antigen expression in melanocytic lesions.
Advanced steps of tumor progression are generally characterized by an increased growth fraction within the neoplastic cell population. The presence of a relevant growth fraction is also related to widely accepted prognostic parameters in some human malignancies. Our aims were to evaluate the presence of a growth fraction with Ki67 monoclonal antibody (MoAb), and to correlate it with tumor progression and HLA-DR antigen expression in 88 melanocytic lesions. The lesions were 19 acquired melanocytic nevi, 58 primary melanomas [divided into 26 superficial spreading melanomas (SSM), 24 superficial spreading melanomas with nodular areas (SS + NM), and five nodular melanomas (NM)], and 11 metastases from malignant melanomas. Ki67 MoAb stained 16%, 19%, 71%, 100%, and 82% of nevi, SSM, SS + NM, NM, and metastases, respectively. Among primary melanomas, Ki67 MoAb stained 12%, 28%, 50%, and 70% of tumors less than 0.75, 0.75-1.49, 1.5-2.9, and greater than or equal to 3 mm thick, respectively. A concordant reactivity pattern for Ki67 and HLA-DR antigens was found in 72% of lesions (p less than 0.0001). We have shown that a representative growth fraction (ie, Ki67 reactivity) is present in melanocytic lesions only in advanced steps of tumor progression and correlates with HLA-DR antigen expression. Despite the different biologic values of Ki67 and HLA-DR antigens, we suggest the joint evaluation of both antigens as a useful marker of aggressive behavior in melanoma.


[The role of melatonin in the development of post-stroke cognitive impairment in elderly patients in comparison with middle-aged patients].
In the acute phase of ischemic stroke 73 patients aged from 61 to 86 years and 47 patients aged 36 to 60 years underwent a comprehensive neuropsychological testing, evaluation of the concentration of 6-sulfatoximelatonin 6-sulfatoximelatonin in the night urine and brain MRI morphometry in some patients. The control group consisted of 14 persons without cerebrovascular disease. Younger and middle-aged patients had higher levels of 6-sulfatoximelatonin compared to both controls and elderly patients. The level of the metabolite in patients older than 60 years and the control group did not differ. In the group of patients older than 60 years we revealed a direct correlation with the severity of the stroke and concentration of 6-sulfatoximelatonin. Metabolite concentration was inversely correlated with the results of the Mini Mental State Examination, Frontal Assessment Battery, verbal fluency, clock drawing test and directly - with the Shulte tables result. High concentrations of 6-sulfatoximelatonin was also associated with a large size of acute ischemic lesion and hippocampal volume. The highest concentration of the metabolite was observed in patients with dysexecutive cognitive impairment and the lowest in patients with normal cognitive status and amnestic deficit. Thus, in elderly patients a high concentration of 6-6-sulfatoximelatonin is a marker "pure" post-stroke cognitive impairment, whereas a low concentration of metabolite in the presence of cognitive deficits may be indicative of its mixed, that is, in part, of hippocampal type.


Variation in the reproductive strategy of a lichenized fungus along a climatic gradient.
Onset of reproduction and reproductive allocation patterns are key components of plant reproductive strategies. Life history theory predicts that plants in adverse environments for juvenile performance start reproduction at smaller sizes and exhibit higher reproductive allocation compared to their counterparts in favourable environments. Life history theory will gain in generality if its predictions are shown to apply to a broad range of organisms and modes of reproduction. This study tested whether the asexual reproductive strategy of a lichenized fungus changed along a climatic gradient. The variation in threshold size for asexual reproduction and asexual reproductive allocation of the lichen Lobarina scrobiculata was assessed in 18 populations (9665 individuals) along a climatic gradient spanning 800 km in latitude in Southern Europe. Using generalized linear models and standardized major axis regressions, the allometric relationships and the associated variation in climatic factors according to the changes in the threshold size for reproduction and reproductive allocation patterns were assessed. The onset of reproduction was size-dependent and the reproductive allocation increased with individual size. Both the threshold size for reproduction and the reproductive allocation varied along the rainfall gradient. A lower threshold size for reproduction and higher reproductive allocation in drier, adverse locations were found. Therefore, populations in drier locations fitted the predictions of life history theory for sexually reproducing organisms in adverse environments for juvenile performance. This study highlights the applicability of the life history theory to fungi and to modes of reproduction other than sexual reproduction. Based on the intraspecific variation in the asexual reproductive strategy of a fungal organism with climatic factors, these findings expand the scope of life history theory predictions and increase our understanding of life history diversity and reproductive strategies across environments.


Investigation of brain tissue infiltration by medulloblastoma cells in an ex vivo model.
Medulloblastoma (MB) is a paediatric cancer of the cerebellum that can develop cerebellar and leptomeningeal metastases. Local brain tissue infiltration, the underlying cause of metastasis and relapse, remains unexplored. We developed a novel approach to investigate tissue infiltration of MB using organotypic cerebellum slice culture (OCSC). We show that cellular and structural components of cerebellar tissue in OCSCs are maintained for up to 30 days ex vivo, and that OCSCs foster tumour growth and cell proliferation. Using cell-based models of sonic hedgehog (SHH) and group 3 (G3) MB, we quantified tumour growth and infiltration and determined the morphological characteristics of the infiltrating cells. We observed basal levels of dissemination occurring in both subgroups with cells migrating either individually or collectively as clusters. Collective cerebellar tissue infiltration of SHH MB cells was further enhanced by EGF but not HGF, demonstrating differential tumour cell responses to microenvironmental cues. We found G3 cells to be hyper proliferative and observed aggressive tumour expansion even in the absence of exogenous growth factors. Our study thus provides unprecedented insights into brain tissue infiltration of SHH and G3 MB cells and reveals the cellular basis of the tumour progressing functions of EGF in SHH MB.


Patient non-adherence: an interpretative phenomenological analysis.
Purpose While interpretative phenomenological analysis (IPA) has been used in health psychology research, it has so far not been applied to seek deeper insights into the patients' experiences about treatment. The purpose of this paper is to address this gap by using IPA to understand patient non-adherence. Design/methodology/approach In total, 18 patients with chronic conditions seeking healthcare services in Goa and Karnataka, India, were selected by using the snowball sampling method. In-depth interviews were conducted face to face. A semi-structured questionnaire developed by the researchers was used to collect the data. IPA was used to explore the themes to predict patient non-adherence. Findings The study results indicate that economic factors, health system related factors, social factors and psychological factors impact patient non-adherence. Patient non-adherence includes medication non-adherence and lifestyle modification non-adherence. Research limitations/implications Being cross sectional in design, the results may not be as appropriate as the results derived from a longitudinal study given that non-adherence occurs over time. Practical implications Patient non-adherence is a global health issue. Multidisciplinary approach to enhance patient adherence to treatment should form part of public healthcare policy. Social implications Exploring the factors influencing patient non-adherence will help the health-care industry stakeholders to reduce healthcare cost and improve patient's quality of life. Originality/value Although there is extensive quantitative research on the prevalence of non-adherence, qualitative research is limited. This paper addresses this gap by using IPA to understand patient non-adherence and its factors and dimensions.


Combined seed and foliar pre-treatments with exogenous methyl jasmonate and salicylic acid mitigate drought-induced stress in maize.
Susceptibility of plants to abiotic stresses, including extreme temperatures, salinity and drought, poses an increasing threat to crop productivity worldwide. Here the drought-induced response of maize was modulated by applications of methyl jasmonate (MeJA) and salicylic acid (SA) to seeds prior to sowing and to leaves prior to stress treatment. Pot experiments were conducted to ascertain the effects of exogenous applications of these hormones on maize growth, physiology and biochemistry under drought stress and well-watered (control) conditions. Maize plants were subjected to single as well as combined pre-treatments of MeJA and SA. Drought stress severely affected maize morphology and reduced relative water content, above and below-ground biomass, rates of photosynthesis, and protein content. The prolonged water deficit also led to increased relative membrane permeability and oxidative stress induced by the production of malondialdehyde (from lipid peroxidation), lipoxygenase activity (LOX) and the production of H2O2. The single applications of MeJA and SA were not found to be effective in maize for drought tolerance while the combined pre-treatments with exogenous MeJA+SA mitigated the adverse effects of drought-induced oxidative stress, as reflected in lower levels of lipid peroxidation, LOX activity and H2O2. The same pre-treatment also maintained adequate water status of the plants under drought stress by increasing osmolytes including proline, total carbohydrate content and total soluble sugars. Furthermore, exogenous applications of MeJA+SA approximately doubled the activities of the antioxidant enzymes catalase, peroxidase and superoxide dismutase. Pre-treatment with MeJA alone gave the highest increase in drought-induced production of endogenous abscisic acid (ABA). Pre-treatment with MeJA+SA partially prevented drought-induced oxidative stress by modulating levels of osmolytes and endogenous ABA, as well as the activities of antioxidant enzymes. Taken together, the results show that seed and foliar pre-treatments with exogenous MeJA and/or SA can have positive effects on the responses of maize seedlings to drought.


Ceftriaxone vs. ampicillin + metronidazole as prophylaxis against infections after clean-contaminated abdominal surgery.
In a prospective, controlled, double-blind study, 496 patients undergoing abdominal surgery were given antibiotic prophylaxis with a single dose of either ceftriaxone or ampicillin + metronidazole. No significant intergroup difference was found between the respective overall rates of infectious complications (3.2% and 4.9%). Analysis of the microbiologic findings showed incisional wound infections, mainly caused by gram-negative rods, to be more common in the ampicillin-metronidazole group, whereas deep wound infections were more frequent in the ceftriaxone group. It is concluded that ceftriaxone seems to be more efficient than ampicillin-metronidazole as prophylaxis against incisional wound infection, but should preferably be supplemented with an antianaerobic agent to prevent deep wound infections.