Povidone-iodine vs chlorhexidine alcohol for skin preparation in malignant and premalignant gynaecologic diseases: A randomized controlled study.
To compare povidone-iodine with chlorhexidine alcohol solutions for the prevention of surgical site infection (SSI) in malignant and premalignant gynaecologic diseases, and to evaluate the effects of temperature on SSI at 25 °C and 37 °C. This was a randomized controlled trial of a cohort of 220 patients undergoing surgery for malignant or premalignant conditions. Preoperative skin preparations were performed with 10% povidone-iodine at 25 °C (PI), 10% povidone-iodine at 37 °C (warm PI), 4% chlorhexidine gluconate with alcohol at 25 °C (CH) and 4% chlorhexidine gluconate with alcohol at 37 °C (warm CH) for each group. All women included in the study received 1 g intravenous cefazolin antibioprophylaxis 30 min before skin incision. The primary outcome was SSI within 30 days of surgery, and secondary outcomes were identification of the causative organism and clinical factors that may be associated with SSI. SSIs were detected in 24 (10.9%) patients. Except for two organ/space-specific SSIs, all were superficial SSIs. The frequency of SSI was significantly lower in the warm PI group than in the PI group (p = 0.032). There were no significant differences in the frequency of SSI between the groups in other binary comparisons. In addition, there was no significant difference between both povidone-iodine groups compared with both chlorhexidine alcohol groups in terms of the development of SSI (10.9% vs 11%, p = 1.00). SSI caused by micro-organisms was found in 18 patients, and Enterococcus faecalis was the most common reproducing organism in wound culture. Patients with SSI were significantly older (58.9 ± 11.4 vs 52.8 ± 12.3 years) and more likely to be readmitted to hospital [15 (62.5%) vs 9 (37.5%)] than patients without SSI. SSI rates can be reduced by warming povidone-iodine, but this effect could not be demonstrated with chlorhexidine solutions. When both groups of povidone-iodine were compared with both groups of chlorhexidine alcohol, no significant difference was found in the prevention of SSI in malignant and premalignant gynaecologic operations.


Addressing the burden of group A streptococcal disease in India.
Group A streptococcus-associated disease and sequelae continue to have devastating effects on public health and national economy as they mainly affect children and young adults. There is an urgent need for wider application of methods of primary prevention, in the form of optimal diagnosis and management of the simple group A streptococcal sore throat. This review article briefly summarizes the burden of streptococcal disease in India, and discusses treatment options standardized by the World Health Organization. Penicillin continues to remain the drug of choice for treating group A streptococcal pharyngitis and for prevention of acute rheumatic fever in non-allergic patients. Also discussed in this review are contemporary thoughts on streptococcal "carriers", recurrent infections, antibiotic treatment "failures" and emergence of drug resistance among group A streptococci.


Germline TP53 c.566C>T mutation incidentally diagnosed during treatment for acute myeloid leukemia: A case report.
TP53 mutations in acute myeloid leukemia (AML) are associated with poor outcomes. The number of somatic and/or germline genetic tests for therapy is increasing. Patients with such incidental findings should undergo adequate genetic counseling.


Identification of novel exons and transcripts by comprehensive RNA-Seq of horn cancer transcriptome in Bos indicus.
Horn cancer (HC) is a widely prevalent cancer amongst Bos indicus cattle and frequently associated with economic losses due to reduction in draught and milk production capacity. To identify novel transcripts and characterize HC transcriptome, we employed high throughput RNA-Seq analysis of HC and horn normal (HN) tissue. Total of 584,450 and 920,450 high quality reads were analyzed for HN and HC tissue, respectively, resulting in the identification of 16,803 unique genes comprising of 14,754 annotated genes and 2049 novel transcripts. We found 251 significant differentially expressed genes in HC transcriptome, which includes 52 putative novel transcripts. We validated presence of 23 out of 28 novel transcripts by RT-PCR and confirmed differential expression of 12 novel transcripts through RT-qPCR on 4 samples each of HC and HN. Functional analysis revealed that HC is characterized by deregulation of genes involved in epithelial cell differentiation and complement cascade. Our study will serve as a step further in detailed characterization of HC transcriptome and provide firm base to explore and mitigate HC at finer resolution.


Spinal fusion for single-level SPECT/CT positive lumbar degenerative disc disease: the SPINUS I study.
With current imaging modalities and diagnostic tests, identifying pain generators in patients with non-specific chronic low back pain (CLBP) is difficult. There is growing evidence of the effectiveness of SPECT/CT examination in diagnosing the source of pain in the spine. The study aims to investigate the effect of posterior interbody fusion on a single-level SPECT/CT positive lumbar degenerative disc disease (DDD). This is a prospective study of patients with chronic low back pain (CLBP) operated on for a single-level SPECT/CT positive DDD. Primary outcomes were changes in visual analogue scale (VAS) scores and the Oswestry Disability Index (ODI). Secondary outcomes were complications, return to work, satisfaction and willingness to re-undergo surgery. During a 3-year period, 38 patients underwent single-level fusion surgery. The mean preoperative VAS score of 8.4 (± 1.1) decreased to 3.2 (± 2.5, p < 0.001) and the mean preoperative ODI of 51.5 (± 7.3) improved to 20.7 (± 14.68, p < 0.001) at a 2-year follow-up. A minimum clinically important difference (30% reduction in VAS and ODI) was achieved in 84.2% of patients. Some 71% of patients were satisfied with the surgery results and 89.4% would undergo surgery again. There were four complications, and two patients underwent revision surgery. Some 82.9% of patients returned to work. Fusion for one-level SPECT/CT positive lumbar DDD resulted in substantial clinical improvement and satisfaction with surgical treatment. Therefore, SPECT/CT imaging could be useful in assessing patients with CLBP, especially those with unclear MRI findings. ClinicalTrials.gov Identifier: NCT04876586.


[Alloalbuminemia associated with myeloma].
Alloalbuminemia occurring together with paraproteinemia in a case of proven myelomatosis is described. The clinical and laboratory findings of this case are listed. The importance of the reported case is emphasized.


Tracheal surgery in children.
The aim of this study is to show that five distinct types of tracheal anomalies should be differentiated with respect to therapy and prognosis. The records of 12 infants and children seen over a period of 20 years for different tracheal anomalies such as laryngotracheal stenosis (n = 3), long or short-segment stenosis of the upper (n = 2), middle (n = 6), and lower (n = 1) trachea were reviewed. In addition to these 12 patients with congenital stenosis, 3 other patients needed tracheal resections because of oncologic or traumatic disease: in 2, the trachea was infiltrated by a papillary carcinoma of the thyroid gland and in one, the upper part of the trachea was injured by an oral explosion accident. 25 patients presenting during the same period for other tracheal pathologies including esophagotracheal cleft syndrome (n = 7), tracheomalacia (n = 4), total tracheal agenesis (n = 3), or for placement of a tracheostomy (n = 11) due to other diseases were excluded from this study. There was 1 early death after repair of a laryngotracheal stenosis by cricoid-split and cricoid-splint due to both cerebral hemorrhage and cardiac insufficiency secondary to Fallot's tetralogy. Another child died four weeks after slide tracheoplasty as a result of hypoxic cerebral lesions induced by severe central catheter-related septicemia. One child with therapy-resistant obstructing granulation tissue which developed after a slide tracheoplasty required a tracheostomy. The patient with the tracheal injury died after another accident one year after discharge. All other patients (n = 11) are doing well. With respect to therapy of congenital and post-intubation tracheal stenosis, four types should be distinguished. Each of these types requires an adequate surgical procedure. The most important postoperative problem in tracheal surgery is the development of granulation tissue. However, the pathogenesis of granulation is still unknown.


Regulation of platelet protein kinase C by oleic acid. Kinetic analysis of allosteric regulation and effects on autophosphorylation, phorbol ester binding, and susceptibility to inhibition.
The regulation of protein kinase C by oleic acid was studied, and parameters that characterize the activation of protein kinase C by oleic acid and distinguish its effects from those of diacylglycerol (DAG) and phosphatidylserine (PS) were delineated. Activation of protein kinase C by sodium oleate required the presence of calcium and showed mild cooperative behavior (Hill number of 1.25) suggesting that Ca(oleate)2 is the active species. Kinetic analysis of the interaction of sodium oleate with substrates indicated that sodium oleate acted to increase the activity of the enzyme without modulating the KM for either MgATP or histone substrates. In this respect, sodium oleate action resembled that of DAG but not PS. However, multiple parameters distinguished the effects of sodium oleate from those of DAG. Unlike DAG, sodium oleate was unable to inhibit phorbol dibutyrate binding to protein kinase C. Sodium oleate also failed to interact with micelle-bound protein kinase C and preferentially activated "soluble" protein kinase C. The addition of histone caused protein/lipid aggregation in the presence of DAG but not in the presence of oleate. Activation of protein kinase C by sodium oleate or by PS/DAG demonstrated differential susceptibility to the action of inhibitors. Sphingosine and NaCl were more potent in inhibiting activation of protein kinase C by PS/DAG than by sodium oleate. Sodium oleate also expressed PS-like activity in that calcium and oleate acted as cofactors in activation of protein kinase C by DAG. Similar to PS, the ability of oleate to act in synergy with DAG resulted from "competitive" activation with a decrease in KM(app) of protein kinase C for DAG. Finally, sodium oleate was unable to induce autophosphorylation of protein kinase C. These studies demonstrate that oleate activates protein kinase C by a mechanism that is distinct from PS/DAG but partially overlaps the kinetic effects of both PS and DAG. The significance of these studies is discussed in relation to mechanisms of protein kinase C activation and to the possible physiological relevance of activation of protein kinase C by fatty acids.


Inhibition of platelet aggregation and antagonism of vasopressin-induced ECG changes in primates by a carboprostacyclin analogue, ZK 36374.
A chemically stable carboprostacyclin analogue, ZK 36374 has been compared with two other prostacyclin derivatives with respect to ADP-induced in vitro aggregation of baboon and human platelets and ex vivo platelet aggregation in the baboon. ZK 36374 was also tested on the systemic arterial blood pressure of the baboon and against vasopressin-induced ECG changes in primates. Compared to the other two compounds, ZK 36374 displayed enhanced anti-platelet aggregating activity; there was dissociation between this property and its hypotensive potency. ZK 36374 antagonized the vasopressin-induced ECG changes. These results indicate that ZK 36374 possesses therapeutic potential in vascular disease including that affecting the coronary vessels.


Searching for certainty: findings predictive of appendicitis in equivocal ultrasound exams.
Ultrasound (US) is the preferred imaging modality for evaluating suspected pediatric appendicitis. However, borderline appendiceal enlargement or questionable inflammatory changes can confound interpretation and lead to equivocal exams. The purpose of this study was to determine which findings on equivocal US exams are most predictive of appendicitis. All US exams performed for suspected pediatric appendicitis from July 1, 2013, through July 9, 2014, were initially interpreted using a risk-stratified scoring system. Two blinded pediatric radiologists independently reviewed US exams designated as equivocal and recorded the following findings: increased wall thickness, loss of mural stratification, peri-appendiceal fat inflammation, peri-appendiceal fluid, appendicolith and maximum appendiceal diameter. A third pediatric radiologist resolved discrepancies. US features were correlated with the final diagnosis via multivariate analysis. During the study period, 162/3,750 (4.3%) children had US exams initially interpreted as equivocal (mean age 9.8 +/- 3.8 years). Five outpatients were lost to follow-up. Forty-eight of the remaining 157 (30.6%) children had an operative diagnosis of appendicitis. Findings significantly associated with appendicitis were loss of mural stratification (odds ratio [OR] = 6.7, P=0.035), peri-appendiceal fat inflammation (OR = 10.0, P<0.0001) and appendicolith (OR = 15.8, P=0.025). While appendiceal diameter tended to be larger in patients with appendicitis, the difference was not statistically significant. Loss of mural stratification, peri-appendiceal fat inflammation and an appendicolith are significant predictors of appendicitis in children with otherwise equivocal US exams. While maximum appendiceal diameter is not statistically associated with appendicitis in our study, mean appendiceal diameter of 6.7 mm in those without appendicitis suggests that the customary upper normal limit of 6 mm is too sensitive.


Management of stable COPD.
Chronic obstructive pulmonary disease (COPD) is a systemic disease with major impact worldwide. In the treatment of COPD a holistic approach should be taken. In order to reach this, an individual treatment plan should be made which includes at least elements of smoking cessation, optimisation of pulmonary status by pharmacotherapy and exercise embedded in a new lifestyle. Furthermore, more research on nutritional and metabolic intervention strategies for COPD patients is needed. With the availability of all these treatment options, a nihilistic attitude toward the patient with COPD is no longer justified.


The correlation between total deceleration and acceleration surface areas on electronic fetal monitoring and neonatal cord blood pH in postdate pregnancies.
To assess the correlation between the total decelerations area in the final 120 min before delivery and neonatal cord blood pH in postdate pregnancies. This cross-sectional study included women with gestational age greater than 41 weeks, singleton pregnancy, and a category II electronic fetal monitoring (EFM) of at least 30 min during the final 120 min before delivery. We included postdate deliveries of an otherwise low-risk parturient population. Each area was calculated as duration × depth × 1/2. Correlations were tested using the Spearman correlation coefficient. A total of 100 EFMs were included in the analysis. Median pH was significantly lower in neonates above the median total deceleration area under the curve (AUC; 7.26 vs. 7.32, P = 0.002). Gestational age at delivery was independently associated with total deceleration AUC above median (adjusted odds ratio 1.21, 95% confidence interval 1.09-1.37) controlling for history of previous cesarean delivery and duration of second stage of labor. A significant correlation was found between cord blood pH and total deceleration area (P < 0.001, Spearman correlation coefficient -0.37). Among women with postdate pregnancies, the total deceleration area and the mean maximum duration of decelerations were negatively correlated with cord blood pH. Further studies are needed to incorporate deceleration area as a method in predicting fetal acidemia.


Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19.
Diabetes is associated with increased mortality from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2), the key entry factor for SARS-CoV-2 infection. Specifically, we analyzed five public scRNA-seq pancreas datasets and performed fluorescence in situ hybridization, western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) cases. These in silico and ex vivo analyses demonstrated prominent expression of ACE2 in pancreatic ductal epithelium and microvasculature, but we found rare endocrine cell expression at the mRNA level. Pancreata from individuals with COVID-19 demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression that was primarily limited to ducts. These results suggest SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, is an unlikely central pathogenic feature of COVID-19-related diabetes.


Aerosol Inhalation-mediated Delivery of an Adeno-associated Virus 5-expressed Antagonistic Interleukin-4 Mutant Ameliorates Experimental Murine Asthma.
T helper 2 (Th2) lymphocytes and associated interleukin (IL) 4 and IL-13 play crucial roles in asthma pathogenesis. In this study, we explored an adeno-associated virus 5 (AAV5) based gene therapy by delivering truncated IL-4 protein to antagonize IL-4 receptor α chain and interrupt asthmatic signal pathway. A recombinant adeno-associated virus 5 (AAV5) vector harboring a truncated mouse IL-4 gene (AAV5-mIL-4ΔC22) was prepared. Western blotting showed that the IL-4 mutant protein lacking the C-terminal 22 amino acids was expressed well in AAV5-mIL-4ΔC22 infected 16HBE and BEAS-2B cells. AAV5-drivn green fluorescent protein (AAV5-GFP) served as a control. The biodistribution of vector DNA after AAV5 vector aerosol inhalation was examined by PCR and the result showed that foreign DNA was detectable in the lungs but not in other organs including gonads. The aerosol inhalation-mediated delivery of AAV5-expressed antagonistic IL-4 mutant protein improved the lung function of ovalbumin-induced asthma mice. The inhalation of aerosolized AAV5-mIL-4ΔC22 significantly improved the lung function and modulated the immune cell infiltration and associated cytokine expression in the bronchoalveolar lavage fluid (BALF) of ovalbumin-induced asthma mice.


Growing skull fracture in a child with Ehlers-Danlos syndrome: case report and literature review.
Growing skull fracture (GSF) is a rare complication of head trauma in the pediatric population, commonly observed in children younger than 3 years. In this report, the authors describe a case of a 3-year-old male child, with clinical features of Ehlers-Danlos syndrome (EDS), who developed a GSF in frontal bone after a crib fall, treated with duraplasty and cranioplasty with autologous craft. Here, pertinent literature was reviewed with an emphasis on surgical techniques, and correlation with the mentioned syndrome. This is the first case of GSF in association with EDS in the literature. The relevance of the case described concerns the rarity of the condition itself, the atypical presentation, and the intraoperative findings, which showed the important fragility of the dura mater, probably due to EDS. Therefore, this syndrome, besides having influenced the pathogenesis, was also a challenging factor in the surgical treatment.


Assessment by autonomic blockade of age-related changes of the sinus node function and autonomic regulation in sick sinus syndrome.
Age-related changes of the sinus node (SN) function and the autonomic influence on the SN function were evaluated in 65 patients with sick sinus syndrome (range 14 to 84 years). Heart rate (HR), corrected SN recovery time and sinoatrial conduction time were measured before (basic) and after (intrinsic) autonomic blockade (propranolol 0.2 mg/kg plus atropine 0.04 mg/kg intravenously). Percent of autonomic chronotropies of the SN function were calculated by the following formulas: (1)--(intrinsic HR--basic HR/intrinsic HR) X 100; (2) (intrinsic corrected SN recovery time--basic corrected SN recovery time/intrinsic corrected SN recovery time) X 100; (3) (intrinsic sinoatrial conduction time--basic sinoatrial conduction time/intrinsic sinoatrial conduction time) X 100. Basic HR, basic corrected SN recovery time and basic sinoatrial conduction time did not vary with age. Intrinsic HR decreased with age, but this correlation was weak (r = -0.54, p less than 0.001). Intrinsic corrected SN recovery time and intrinsic sinoatrial conduction time tended to increase with age (r = 0.26, p less than 0.05; r = 0.29, p less than 0.05, respectively). Percent chronotropies of HR, corrected SN recovery time and sinoatrial conduction time were negative values in younger patients and positive values in elderly patients; they correlated positively with age (r = 0.59, p less than 0.001; r = 0.60, p less than 0.001; r = 0.43, p less than 0.001, respectively). Thus, the basic SN function did not change with age, while the intrinsic SN function deteriorated with age.(ABSTRACT TRUNCATED AT 250 WORDS)


NMR and spin relaxation in systems with magnetic nanoparticles.
The ¹H NMR spectra and spin dynamics of the host systems have been studied in liquid and solid suspensions of γ-Fe₂O₃ nanoparticles. Significant broadening of ¹H NMR spectra and growing relaxation rates were observed with increased concentration of nanoparticles in the liquid systems, with the relation T₁/T₂ depending on the particular host. Solid systems demonstrate inhomogeneous broadening of the spectra and practically no dependence of T₁ upon the nanoparticle concentration. We explain the experimental results taking into account the predomination of self-diffusion as a source of the relaxation in liquid suspensions, and estimate effective parameters of relaxation in the systems under study.


Elucidating absolute configuration of unsaturated alcohols via enantioselective acylation reactions.
Enantioselective nucleophilic acylation catalysis provides a simple method of determining absolute configuration for unsaturated alcohols. Extension of this technique to natural products and synthetic compounds, as well as current limitations of this approach, are also described.


Sideroxylonal in Eucalyptus foliage influences foraging behaviour of an arboreal folivore.
Plant secondary metabolites (PSMs) offer plants chemical defences against herbivores, and are known to influence intake and diet choice in both insect and mammalian herbivores. However, there is limited knowledge regarding how PSMs influence herbivore foraging decisions. Herbivore foraging decisions, in turn, directly impact on which individual plants, and plant species, are selected for consumption. We took advantage of the natural variation in sideroxylonal concentrations in the foliage of Eucalyptus melliodora (Cunn. ex Schauer) to investigate feeding patterns of a marsupial folivore, the common ringtail possum, Pseudocheirus peregrinus (Boddaert 1785). Foliage, collected from six trees, contained between 0.32 and 12.97 mg g-DM(-1) sideroxylonal. With increasing sideroxylonal concentrations, possums decreased their total intake, rate of intake and intake per feeding bout, and increased their cumulative time spent feeding. Possums did not alter their total feeding time, number of feeding bouts or time per feeding bout in response to increasing sideroxylonal concentrations. Results demonstrate important behavioural changes in foraging patterns in response to sideroxylonal. These behavioural changes have important implications, in relation to altered foraging efficiency and potential predation risk, for herbivores foraging in the field. As a result, the spatial distribution of dietary PSMs across a landscape may directly influence herbivore fitness, and ultimately habitat selection of mammalian herbivores.


Selection and evaluation of Azospirillum brasilense strains growing at a sub-optimum temperature in rhizocoenosis with wheat.
Fourteen Azospirillum brasilense strains growing at a sub-optimum temperature were selected based on their ability to grow and carry out plant growth promoting activities at 22 degrees C. The strains were tested for their response to inoculation in wheat (two popular cultivars, HD2285 and WH547, under sterile conditions) crop using sterile and nonsterile rooting medium. Significant increase in plant growth parameters was observed; the overall response to inoculation was better in cultivar HD2285. Based on their performance under sterile conditions, 4 strains were selected and compared under nonsterile conditions with strain sensitive to a sub-optimum temperature in pots using wheat variety HD2285. The strains capable of growing at the sub-optimum temperature can colonize the wheat endorhizosphere efficiently and improve the plant growth and yield as compared to sensitive strain; a 25-27% increase in grain yield was found on inoculating two selected strains compared to NO3- control.


Bothrops jararaca snakes produce several bothrojaracin isoforms following an individual pattern.
More than one isoform of bothrojaracin (BJC), a potent and specific thrombin inhibitor isolated from Bothrops jararaca venom, has been found in individual venoms collected from adult snakes. Variations in snake venom composition have previously been associated with factors such as age, sex, geographic origin, season of the year and diet. In order to obtain further information concerning individual patterns of expression of BJC isoforms, we have analyzed five individual Bothrops jararaca snake venoms collected at the same time from adult female snakes from the same geographic region. As expected, crude venoms showed a similar migration pattern on SDS-PAGE. BJC was purified using a procedure which includes an affinity chromatography step (PPACK-thrombin Sepharose). A slight variation in the amount of BJC obtained from individual venom samples was noticed. Inhibition of thrombin-induced platelet aggregation as well as migration pattern on SDS-PAGE (under reducing and non-reducing conditions) and isoelectric focusing varied considerably among BJC samples from the five snakes. The amino-terminal sequences (residues 1-34) of individual BJC samples were compared with the sequence deduced from isolated cDNAs encoding alpha and beta chains of BJC. A high degree of homology was detected, although some residues differed from one sample to other. Altogether, data confirmed the heterogeneity found for BJC purified from individual snakes. Thus, the results indicate that: (1) individual specimens of Bothrops jararaca have different patterns of BJC isoform expression; and (2) it seems that genetic factors, at least in part, determine the variability found in BJC production.


Knowledge of blood pressure levels and targets in patients with coronary artery disease in the USA.
Little is known about patient awareness of nationally recommended blood pressure targets, especially among patients with cardiac disease. To examine this issue, we interviewed 738 patients hospitalized with coronary artery disease to assess their knowledge of their systolic and diastolic blood pressure levels as well as corresponding national targets. We used bivariate and multivariate analyses to determine if any patient demographic or clinical characteristics were associated with blood pressure knowledge. Only 66.1% of patients could recall their own systolic and diastolic blood pressure levels. Only 48.9% of all patients could correctly name targets for these values. Knowledge of target blood pressure levels was particularly poor among patients who were female (odds ratio (OR) 0.69; 95% confidence interval (CI) 0.49-0.98), aged > or =60 years (OR 0.70, CI 0.51-0.97), without any college education (OR 0.48, CI 0.35-0.65), without a documented history of hypertension (OR 0.57, CI 0.39-0.84), and with known diabetes (OR 0.46, CI 0.33-0.66). Patients in the highest risk group, according to Joint National Committee guidelines stratification, were no more knowledgeable about their blood pressure levels and targets than lower risk patients. A significant proportion of patients hospitalized with coronary artery disease do not know their own blood pressure levels or targets. Current blood pressure education efforts appear inadequate, particularly for certain patient subgroups in which hypertension is an important modifiable risk factor.


Assessment of soil erosion hazard and its relation to land use land cover changes: Case study from alage watershed, central Rift Valley of Ethiopia.
Soil erosion by water and wind is among the most crucial land degradation processes in Ethiopia. This is also the case for Alage watershed located in the cental Rift Valley system. This study aimed at assessment of soil erosion hazard and its relation to land use land cover change in the watershed during the period from 1984 to 2016 for a better land management. The study is based on application of Remote Sensing (RS) and Geographical Information System (GIS) to extract inputs factor values for the Revised Universal Soil Loss Equation (RUSLE). Time-series satellite imageries of Landsat TM 1984, ETM+ 2000 and OLI 2016 were used for land use land cover change detection and determination of cover management (C) factor of the RUSLE. Biophysical data such as rainfall, soil properties, land management practices including soil and water conservation measures within the watershed were collected using field survey and secondary data sources. Slope steepness and slope length factors were derived using Digital Elevaition Model (DEM). Long-term average annual soil loss rates were estimated by the RUSLE integrated with GIS for 1984, 2000 and 2016. Using satellite imageries, the land use land cover and changes within the watershed during the three periods were obtained through a supervised classification with maximum likelihood algorithim. The results of land use land cover change indicated that the proportion of rain-fed cropland, bare land and built up areas increased by 17.4%, 5.9% and 2.9% respectively over the three study period. In contrast the proportion of bush/shrub land, irrigated cropland, grass land, forested areas and waterbodies decresaed by 15.5%, 4.7%, 3.4%, 2.3% and 0.3% respectively during the same period. Estimated average annual soil loss rates showed an increasing trend from 24.3 ton ha-1 yr-1 in 1984 to 38 ton ha-1 yr-1 in 2016. Increasing trends of average annual soil loss rate is attributed to increased proportion of cropland, bare land and built up areas during those periods leading to decreased protective vegetation cover. Hotspot areas within the watershed require implementation of land management practices to prevent further degradation and expansion of gullies. This study is relevant to demonstrate environmental implication of land use land cover change for future land management practices and land use policy in the Rift Valley of central Ethiopia.


Effects of the fatty acid composition of phosphatidylserine and diacylglycerol on the in vitro activity of protein kinase C from rat spleen: influences of (n-3) and (n-6) polyunsaturated fatty acids.
Protein kinase C from rat spleen was assayed with different phosphatidylserines (PtdSer) and diacylglycerols (DAG): PtdSer from bovine brain containing 0.8% 20:4 (n-6), 1.0% 20:5 (n-3) and 5.7% 22:6 (n-3); PtdSer from trout liver lacking 20:4 (n-6) and containing 0.6% 20:5 (n-3) and 43% 22:6 (n-3); 1-stearoyl-2-arachidonylglycerol prepared from synthetic 1-stearoyl-2-arachidonyl-sn-glycero-3-phosphocholine; DAG, prepared from cod roe phospholipids, containing 2.1% 20:4 (n-6), 11.7% 20:5 (n-3) and 29.0% 22:6 (n-3); 1,2-dioleoylglycerol. When assayed with Ca2+ in the absence of DAG there was no difference in the activity of protein kinase C between the two PtdSer. When assayed with Ca2+ in the absence of PtdSer the (n-6)-rich DAG was 2 fold more active, and the (n-3)-rich DAG 1.3 fold more active than 1,2-dioleoylglycerol. When assayed in the presence of both PtdSer and DAG, the enzyme was equally active with all of the DAG, but was 1.3 fold more active with the PtdSer from bovine brain than with the PtdSer from trout liver.


Impact of an inpatient order verification simulation on student perceived preparedness and confidence.
The ability to effectively and efficiently navigate an electronic health record (EHR) to complete an inpatient prospective drug review is a vital skill that entry level practitioners must possess. The purpose of this study was to evaluate the impact of an EHR-based inpatient order verification simulation on students' perceived preparedness and confidence when reviewing the accuracy of an inpatient medication order and providing a verbal recommendation to a health care prescriber. This was evaluated by comparing survey scores pre- and post-simulation. An educational series utilizing EHR technology was designed to simulate the sequence of tasks an inpatient pharmacist completes when processing an inpatient mediation order. This includes performing a prospective drug utilization review to identify medication-related problems, forming alternative recommendations, and verbalizing recommendations to prescriber. A total of 89 students across two cohorts (99%) completed the pre-survey; 31 students (34%) completed the post-survey. Comparison of pre- and post-survey scores resulted in significant findings for all categories: increased perceived preparedness, efficiency, and accuracy when processing or reviewing a medication order (P < .001); increased confidence when efficiently and effectively utilizing EHR technology (P < .001); increased confidence when efficiently (P < .001) and effectively (P < .001) providing a verbal recommendation to a health care prescriber. Incorporating a series of EHR-based activities simulating medication order verification and prescriber communication into the doctor of pharmacy curriculum positively impacts student perceived preparedness and confidence.


Underutilization of Systemic Therapy in Patients With NSCLC Undergoing Pneumonectomy: A Missed Opportunity for Survival.
Recent trials have reported promising results with the addition of immunotherapy to chemotherapy for patients with locally advanced NSCLC, but in practice, the proportion of patients who receive systemic therapy (ST) has historically been low. Underutilization of ST may be particularly apparent in patients undergoing pneumonectomy, in whom the physiologic insult and surgical complications may preclude adjuvant therapy (ADJ). We, therefore, evaluated the use of ST for patients with NSCLC undergoing pneumonectomy. We queried the National Cancer Database, including all patients with NSCLC who underwent pneumonectomy between 2006 and 2018. Logistic regression was used to identify associations with ST and neo-ADJ (NEO). Overall survival was compared after propensity score matching (1:1) patients undergoing ST to those undergoing surgery alone using Kaplan-Meier and Cox regression methods. A total of 2619 patients were identified. Among these, 12% received NEO, 43% received ADJ, and 45% surgery alone. Age younger than 65 years (adjusted odds ratio [aOR] = 1.53, 95% confidence interval; [CI]: 1.10-2.11), Asian ethnicity (aOR = 2.68, 95% CI: 1.37-5.23), treatment at a high-volume center (aOR = 1.39, 95% CI: 1.06-1.81), and private insurance (aOR = 1.42, 95% CI: 1.05-1.94) were associated with NEO, whereas age younger than 65 years (aOR = 1.95, 95% CI: 1.61-2.38), comorbidity index less than or equal to 1 (aOR = 1.66, 95% CI: 1.29-2.16), and private insurance (aOR = 1.47, 95% CI: 1.20-1.80) were associated with any ST. In the matched cohort, ST was associated with better survival than surgery (adjusted hazard ratio = 0.67, 95% CI: 0.58-0.78). A high proportion of patients who undergo pneumonectomy do not receive ST. Patient and socioeconomic factors are associated with the receipt of ST. Given its survival benefit, emphasis should be placed on multimodal treatment strategies, perhaps with greater consideration given to neoadjuvant approaches.


Directly ventricular septal defect closure without using arteriovenous wire loop: Our adult case series using transarterial retrograde approach.
The standard transcatheter ventricular septal defects (VSD) closure procedure is established with arteriovenous (AV) loop and is called as antegrade approach. The directly retrograde transarterial VSD closure without using AV loop might be better option as shortens the procedure time and decreases radiation exposure. Our series consist of twelve sequential adult cases with congenital VSDs (seven with perimembranous, four with muscular, one with postoperative residuel VSD). The mean age was 26.9 (Range 18-58), the mean height was 168.75 cm (Range 155-185cm), and the mean body mass index was 23.4 (Range 17.3-28.4). Maximum and minimum defect sizes were 10 and 5 mm and the mean defect size was 6.24 mm. The procedure was performed with left heart catheterization and advancing the delivery sheath over the stiff exchange wire then VSD occlusion from left side. The defects were successfully closed with this technique in eleven patients. In sixth patient, the defect could not be cannulated by the delivery sheath, as the tip of the sheath did not reach the defect and VSD was closed with same sheath by standard transvenous approach using AV loop. We didn't encounter any complication releated to semilunar or atrioventricular valves. Atrioventricular conduction system was not affected by the procedure in any patients. The median procedure and fluoroscopy times were 66 and 16.5 minutes respectively. Transarterial retrograde VSD closure without using AV loop simplifies the procedure, decreases the radiation exposure, and shortens the procedure time. The only limitation in adult patients is delivery sheath length.


A systematic review and psychometric evaluation of resilience measurement scales for people living with dementia and their carers.
Psychometrically sound resilience outcome measures are essential to establish how health and care services or interventions can enhance the resilience of people living with dementia (PLWD) and their carers. This paper systematically reviews the literature to identify studies that administered a resilience measurement scale with PLWD and/or their carers and examines the psychometric properties of these measures. Electronic abstract databases and the internet were searched, and an international network contacted to identify peer-reviewed journal articles. Two authors independently extracted data. They critically reviewed the measurement properties from the available psychometric data in the studies, using a standardised checklist adapted for purpose. Fifty-one studies were included in the final review, which applied nine different resilience measures, eight developed in other populations and one developed for dementia carers in Thailand. None of the measures were developed for use with people living with dementia. The majority of studies (N = 47) focussed on dementia carers, three studies focussed on people living with dementia and one study measured both carers and the person with dementia. All the studies had missing information regarding the psychometric properties of the measures as applied in these two populations. Nineteen studies presented internal consistency data, suggesting seven of the nine measures demonstrate acceptable reliability in these new populations. There was some evidence of construct validity, and twenty-eight studies hypothesised effects a priori (associations with other outcome measure/demographic data/differences in scores between relevant groups) which were partially supported. The other studies were either exploratory or did not specify hypotheses. This limited evidence does not necessarily mean the resilience measure is not suitable, and we encourage future users of resilience measures in these populations to report information to advance knowledge and inform further reviews. All the measures require further psychometric evaluation in both these populations. The conceptual adequacy of the measures as applied in these new populations was questionable. Further research to understand the experience of resilience for people living with dementia and carers could establish the extent current measures -which tend to measure personal strengths -are relevant and comprehensive, or whether further work is required to establish a new resilience outcome measure.


WITHDRAWN: Reproductive biomechanics: Innovations and challenges.
The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.jbiomech.2015.03.019. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


Magnetic properties of the double perovskites Sm2Mn1+x Co1-x O6 (x = 0, 0.05, 0.12 and 0.26).
The magnetic properties of the double perovskites Sm2Mn1+x Co1-x O6 (x = 0, 0.05, 0.12 and 0.26) were investigated. It was found that the Curie temperature, the lattice parameters and the net magnetic moments increased for increasing amounts of Co. An irreversible behavior was observed by measuring the magnetization after cooling the sample with and without applied magnetic fields (H). The temperature below which the irreversibility was observed is H dependent and the data were nicely fit to de Almeida-Thouless lines. The ac magnetic susceptibility was measured for frequencies f in the range 0.03-10 kHz yielding [Formula: see text] for the shifting in the freezing temperature per decade of f . The spin-dynamics were found to follow a power-law with a product of the critical exponents [Formula: see text] of about 4.99. The overall results are understood within a framework where the variation in the bonding angle associated to the super-exchange interactions are taken into consideration.


Implementing Alfred60AST in a clinical lab: Clinical impact on the management of septic patients and financial analysis.
Sepsis is an important cause of morbidity and mortality. An accelerated microbiology diagnosis is crucial in order to reduce the time to initiate targeted antibiotic therapy. The Alfred60AST system is able to provide phenotypic Antimicrobial Susceptibility Testing (AST) results within hours. This study has two objectives: assess the clinical impact of this technology and determine its cost-effectiveness. During a ten-week period, all new enterobacterial or enterococcal bloodstream infection was analyzed with the Alfred60AST system, in parallel with routine methods. Its impact on the clinician's therapeutic strategy was studied. In order to assess the financial and practical aspects of the method, an analysis of the extracosts and a survey of the technical staff were conducted. Fifty-three cases of bacteriemia were included. For the Enterobacteriaceae bacteriemias, a clinical impact was shown in 18.9% of the cases (e.g, treatment modification). The financial analysis highlighted an increase in costs (+38% for Enterobacteriaceae, +50% for Enterococci), compared to the theoretical costs reported by the firm, due to the workflow and the volumes of samples used. Finally, results of the technical staff survey were favorable in terms of ease of use of the system. In addition to its ease of use, the Alfred60AST system is able to provide an AST in a record time. This study shows a real interest of the technique in the therapeutic management of patients with enterobacterial sepsis. However, its routine implementation requires an increase of the analyzed volumes as well as a 24/7 organization of the laboratory in order to be profitable.


[Immune-mediated inflammatory diseases and psoriasis].
The association of some immune-mediated inflammatory disease in a same patient is known. Nevertheless, this is difficult to appreciate practically for the psoriasis due to the absence of prospective study. The strongest link is with Crohn's disease and the spondyloartropathies. It is sustained by, i) genetic data obtained by genome-wide association study showing some common loci and/or genes involved in innate immunity, ii) immunologic data, these conditions sharing effector cells among which Th17 lymphocytes and inflammatory mediators (TNF-alpha, IL-1,17,23...), that explain the related efficacy of some biologics like anti-TNF-alpha, IL-12/23 antibody and others in progress and iii) environmental triggers among which bacterial infections are probably determining in the genesis of these diseases even if this is still only an hypothesis.


Predictive and prognostic value of preoperative symptoms in the surgical treatment of pulmonary aspergilloma.
Surgical resection is widely accepted as the treatment of choice for pulmonary aspergilloma (PA). However, the technique involved ranks among the most challenging in thoracic surgery and remains associated with considerable morbidity and mortality. To improve the outcomes, it is essential to establish clear recommendations for optimal timing of surgery and selection of patients. To facilitate this, we analyzed the impact of preoperative clinical factors on the results of treatment. Medical records of patients treated surgically for PA between 1979 and 2007 were retrospectively reviewed for clinical variables of potential impact on the surgical outcome with emphasis on preoperative symptoms. Sixty-four patients, including 22 cases of simple aspergilloma and 42 cases of complex aspergilloma were enrolled in the study. Univariable analysis followed by multivariable logistic regression identified weight loss and massive hemoptysis as risk factors for postoperative morbidity [odds ratio (OR) = 8.856, P = 0.006 and OR = 6.9, P = 0.021, respectively]. Ten-year cumulative survival in simple aspergilloma and complex aspergilloma was 88.3% and 70.6%, respectively (P = 0.042). Multivariable analysis by Cox proportional hazard model showed that younger age and lack of massive hemoptysis were independent favorable prognostic factors [hazard ratio (HR) = 1.13, P = 0.0004 and HR = 4.71, P = 0.0319, respectively). Massive hemoptysis is an independent unfavorable predictive and prognostic factor in the surgical treatment of PA. We believe that in operable cases, early surgical resection may be recommended even in asymptomatic patients. This strategy may prevent development of life-threatening symptoms and offers a realistic chance of permanent cure with acceptable mortality and morbidity.


Nuclear survivin expression predicts poorer prognosis in glioblastoma.
Survivin is a member of the inhibitor of apoptosis family, and is expressed in various malignant tumors. Survivin overexpression has been reported to be a poorer prognostic factor in various malignancies. However, the prognostic value of survivin expression in patients with glioblastoma is still controversial. Therefore, in this study the role of survivin as a predictor for survival was investigated in patients with glioblastoma. Tissue specimens were obtained from 66 patients with glioblastoma treated with radiotherapy. Survivin expression was detected by an immunohistochemical method. Nuclear and cytoplasm survivin scores were defined by using the cell positivity and staining intensity. The scores were defined as follows, 0 (no staining), 1 (less than 50% of cell positivity and any staining), 2 (more than 50% of cell positivity and weak to moderate intensity) and 3 (more than 50% of cell positivity and strong intensity). The correlation between survivin scores and the overall survival rate was evaluated. Nuclear and cytoplasm survivin staining were noted in 47 and 58 patients, respectively. The number of patients with nuclear survivin score of 0, 1, 2 and 3, were 19 (28.8%), 26 (39.4%), 9 (13.6%) and 12 (18.2%), respectively. The 3-year overall survival rate of the nuclear survivin score 3 was 0%, significantly lower than the 11.6% of the nuclear survivin score </=2 (P = 0.0003). Cytoplasm survivin score did not correlate with the prognosis. Nuclear survivin expression may be a useful biomarker for predicting prognosis in patients with glioblastoma.


[Post-hepatitic aplasia treated by grafts of allogenic bone marrow. Remission for more than 2 years. Persistance of a total hematopoietic chimera. Graft versus host reaction].
A successfull bone marrow transplant was achieved in a case of post hepatitic aplastic anemia after cyclophosphamide immunosuppression. Caryotype analysis, erythrocytic phenotype and IgG Gm allotype demonstrated evidence of complete chimerism. Anti-thymocyte serum undoubtly was able to suppress a life threatening episode of graft versus host reaction. Severe long lasting skin lesions are now persisting 2 years after the graft.


Spectroscopic studies on [(DD18C6H2)(HPA)2](PA)2 and [(DD18C6H2)(DDQ)2](DDQH)2 formed in the reaction of N,N'-dibenzyl-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane with HPA and DDQ.
The interaction of the mixed oxygen-nitrogen cyclic base, N,N'-dibenzyl-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane (DD18C6) with pi-acceptors such as picric acid (HPA) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) has been studied spectrophotometrically in chloroform at 25 degrees C. The results obtained indicate the formation of 1:4 charge-transfer complexes with the general formula (DD18C6)(acceptor)4. The electronic and infrared spectra of charge-transfer complexes along with the (1)H NMR spectra were recorded and discussed. Based on the data obtained, the complexes were formulated as [(DD18C6H2)(HPA)2](PA)2 and [(DD18C6H2)(DDQ)2](DDQH)2. A general mechanism explaining the formation of the DDQ complex has been suggested.


Impact of levosimendan on platelet function.
Levosimendan has been developed for treatment of severe heart failure. The favorable hemodynamic effect of levosimendan is related to its unique dual mechanism of action - increase of the contractile force of the myocardium caused by enhanced sensitivity of myofilaments to calcium combined with vasodilatation caused by the opening of adenosine triphosphate - dependent potassium channels. Due to the structural similarities to phosphodiesterase inhibitors it may partly exert its action via inhibition of phosphodiesterase inhibitors III. Inhibition of the phosphodiesterase inhibitors III leads to an increase of intracellular concentration of cyclic adenosine monophosphate causing an anti-aggregatory effect. There are some contradictory or indirect and inconclusive reports related to the impact of levosimendan on platelet function. The aim of this systematic review was to critically discuss the impact of levosimendan on platelet function according to currently available knowledge based on the findings of experimental as well as observational and randomized clinical studies.


Perioperative Outcomes of Minimally Invasive Aortic Arch Reconstruction with Branched Grafts Through a Partial Upper Sternotomy.
Ministernotomy has been advocated over recent years as an alternative technique for different cardiovascular surgical procedures to reduce the surgical trauma associated with conventional full sternotomy. In recent years, several reports have addressed minimally invasive approaches to the proximal aorta and aortic arch through a partial upper sternotomy (PUS). We reviewed our experience of minimally invasive open aortic arch reconstruction with a branched graft through a PUS. Between February 2016 and December 2018, 22 patients underwent open arch repair through a PUS. Moderate hypothermic circulatory arrest and antegrade selective cerebral perfusion were used for organ protection. The median patient age was 76 years (range, 65-86). Renal insufficiency was observed in 14 patients (64%) and chronic lung disease, in 11 (50%). Total arch replacement was performed in 20 patients (91%), while the remaining 2 (9%) received partial arch replacement with reconstruction of two supraaortic vessels. Aortic valve replacement with a tissue valve or aortic valve repair was each performed concomitantly in one patient (5%) as a concomitant procedure. The median durations of cardiopulmonary bypass, aortic cross-clamping, and circulatory arrest were 214, 109, and 50 min, respectively. No early deaths, permanent neurological deficits, or spinal cord injuries occurred. One patient (5%) required intraoperative conversion to full sternotomy because of bleeding caused by a venting cannula injury. Three patients (14%) required re-exploration because of bleeding. Prolonged ventilation occurred in 2 patients (9%) with severe chronic obstructive pulmonary disease. Minimally invasive aortic arch reconstruction with branched grafts through a PUS can be safely performed with satisfactory perioperative outcomes.


Taste aversion learning induced by forced swimming in rats.
Two experiments demonstrated that forced swimming endowed rats with aversion to the taste solution consumed before the swimming. In Experiment 1, the rats given a trial of taste-swimming sequence drank less of the taste solution in a later test than did the rats given a taste-alone trial. The rats given a trial of taste-poisoning-swimming sequence, however, drank more of the taste solution in the testing than did the rats given a trial of taste-poisoning sequence. These results suggest that some effects of swimming (e.g., energy expenditure caused by physical exercise) induce conditioned taste aversion although they attenuate taste aversion conditioned by poisoning. The attenuation of poison-induced taste aversion by swimming has been reported in the literature, but the swimming-induced taste aversion is novel. Experiment 2, accordingly, was planned to confirm this phenomenon with a differential conditioning procedure, where one of two taste solutions was paired with swimming while the other was not. After a few repetitions of these two types of trials, the rats' intakes of these two solutions were differentiated to show that swimming has the ability to cause taste aversion.


Diversity among clinical isolates of Proteus penneri detected by random amplified polymorphic DNA analysis.
DNA of thirteen haemolytic Proteus penneri strains of clinical origin, all producing calcium dependent haemolysin and having been derived from four European countries was examined for plasmid profile, and outer membrane protein profile, by random amplified polymorphic DNA-PCR (RAPD-PCR) method, and digestions with restriction endonucleases were performed. All strains contained two large plasmids of approximately 60 and 70 kilobase pairs (kb). In addition, four strains contained a small plasmid of about 6 kb. These four strains produced cell-bound haemolysin only. Outer membrane protein analysis revealed subtle differences between strains. RAPD-PCR with primer I (CCGCAGCCAA) revealed 13 types, whereas primer II (AACGCGCAAC) yielded only two main types of different patterns. Results with primer I suggests a DNA sequence diversity within this species. The RAPD-PCR method provides a fast, economical and reproducible means for the typing of P. penneri. Digestion with restriction endonucleases indicated a high level of DNA methylation in this species.


Cell environment shapes TDP-43 function with implications in neuronal and muscle disease.
TDP-43 (TAR DNA-binding protein 43) aggregation and redistribution are recognised as a hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. As TDP-43 inclusions have recently been described in the muscle of inclusion body myositis patients, this highlights the need to understand the role of TDP-43 beyond the central nervous system. Using RNA-seq, we directly compare TDP-43-mediated RNA processing in muscle (C2C12) and neuronal (NSC34) mouse cells. TDP-43 displays a cell-type-characteristic behaviour targeting unique transcripts in each cell-type, which is due to characteristic expression of RNA-binding proteins, that influence TDP-43's performance and define cell-type specific splicing. Among splicing events commonly dysregulated in both cell lines, we identify some that are TDP-43-dependent also in human cells. Inclusion levels of these alternative exons are altered in tissues of patients suffering from FTLD and IBM. We therefore propose that TDP-43 dysfunction contributes to disease development either in a common or a tissue-specific manner.


Health-related quality of life outcomes in disease-free survivors of mid-low rectal cancer after curative surgery.
The main objective of this study was to investigate health-related quality of life (HRQOL) in terms of symptoms and functional outcomes in disease-free survivors of rectal cancer. Consecutive patients (n = 117) who underwent curative surgery for rectal cancer with a minimum of 2 years' follow-up and whose disease had not recurred were asked to complete the European Organization for Research and Treatment of Cancer QLQ-C30 and its colorectal cancer module (QLQ-CR38). Long-term HRQOL outcomes were compared with reference data from the general population. Relevant clinical data including type of surgery, stage of disease, type of treatment, and early and late complications were collected. Univariate and multivariate regression analyses were performed to investigate associations among covariates. HRQOL functional aspects were similar with that of an age- and sex-matched general population. Although clinically meaningful better outcomes favoring our patients were found for the global health status/HRQOL and the pain scales, constipation was worse in rectal cancer survivors than the general population. Multivariate analysis found that worse physical functioning was associated with increasing age (P < .001), female sex (P < .01), presence of stoma (P < .05), and occurrence of late major complications (P < .05). Worse body image was associated with the presence of stoma (P < .001) and chemoradiotherapy (P < .05). Overall, patients with rectal cancer recover well in the long run, with HRQOL levels comparable to that of the general population. HRQOL outcomes provide valuable data that may be used to improve information disclosure to patients.


Grifolamine A, a novel bis-γ-butyrolactone from Grifola frondosa exerted inhibitory effect on α-glucosidase and their binding interaction: Affinity and molecular dynamics simulation.
A novel bis-γ-butyrolactone grifolamine A (1), the first γ-butyrolactone dimer from nature, together with three known γ-butyrolactones (2-4), was isolated from the byproduct from Grifola frondosa polysaccharides preparation process. The structure and stereochemistry of grifolamine A (1) were elucidated by extensive spectroscopic analysis combined with quantum chemical calculation. The biosynthetic origin of compound 1, as well as 2-4 was proposed. Grifolamine A (1) showed an intense inhibition against α-glucosidase in vitro. The underlying inhibitory mechanism was revealed by surface plasmon resonance (SPR), molecular docking, molecular dynamics (MD) simulation and binding free energy calculation. SPR revealed that grifolamine A exhibited a strong affinity to α-glucosidase with an equilibrium dissociation constant (KD) value of 1.178 × 10-4 M. Molecular docking manifested that grifolamine A sat at the active pocket of α-glucosidase by van der Waals force, alkyl interaction and carbon hydrogen bonds, and consequently changed the micro-environmental structure of α-glucosidase. MD simulation revealed that grifolamine A had high binding affinity to α-glucosidase with average free energy of -25.2 ± 3.2 kcal/mol. Free energy decomposition indicated amino acid residues including PHE298, PHE308, PHE309, PHE155 and ARG310 at the binding pocket played a strongly positive effect on the interaction between grifolamine A and α-glucosidase. Our findings provide valuable information for the design and development of novel α-glucosidase inhibitors based on γ-butyrolactone skeleton.


Wisteria floribunda lectin is associated with specific cell types in the ventral cochlear nucleus of the gerbil, Meriones unguiculatus.
The cochlear nucleus is made up of a number of diverse cell types with different anatomical and physiological properties. A plant lectin, Wisteria floribunda agglutinin, that recognizes specific carbohydrate residues in the extracellular matrix binds to some cell types in the ventral cochlear nucleus but not to cells in the dorsal cochlear nucleus. In the ventral cochlear nucleus, the most intensely labeled cells are octopus cells, a subset of multipolar cells and cochlear root neurons. The multipolar cells that are labeled may correspond to the population that projects to the inferior colliculus.


Difference in characteristics and outcomes of basaloid squamous cell carcinoma and squamous cell carcinoma, usual type in cervix: A population-based study from SEER 18 database.
Cervical basaloid squamous cell carcinoma (BSCC) is a rare variant of squamous cell carcinoma with little recognition. Our objective was to identify difference in characteristics and outcomes between BSCC and squamous cell carcinoma, usual type (SSC, UT). A total of 32 BSCC patients and 6387 SCC, UT patients, diagnosed from 2004 to 2014, were identified using the Surveillance, Epidemiology, and End Results database. More BSCC patients presented with older age as compared to SCC, UT (patients over 40 years old: 87.5% vs 60.5%, P < .01). Univariate survival analysis shows that overall survival (OS) and disease-specified survival (DSS) in the BSCC group were slightly better than SCC, UT group, but without statistical significance. Furthermore, BSCC presented similar prognosis in both DSS and OS compared to SCC, UT when matching other parameters with the propensity score matching methods. BSCC tends to appear in older people. However, BSCC appears to carry a similar prognosis compared to SCC, UT.


Removal of cadmium using MnO2 loaded D301 resin.
MnO2 loaded weak basic anion exchange resin D301 (Anion exchange resin, macroreticular weak basic styrene) as adsorbent has been prepared and applied to the removal of cadmium. The adsorption characteristics have been investigated with respect to effect of pH, equilibrium isotherms, removal kinetic data, and interference of the coexisting ions. The results indicated that the Cd2+ could be efficiently removed using MnO2 loaded D301 resin in the pH range of 3-8 from aqueous solutions with the co-existence of high concentration of alkali and alkaline-earth metals ions. T he saturate adsorption capacity of the Cd2+ was 77.88 mg/g. Theadsorption process followed the pseudo first-order kinetics. The equilibrium data obtained in this study accorded excellently with the Langmuir adsorption isotherm.


Plant Morphogenesis 123: a renaissance in modern botany?
Plants are a group of multicellular organisms crucial for the biosphere on the Earth. In the 17th century, the founding fathers of modern botany viewed the bud as the basic unit undergoing the plant life cycle. However, for many understandable reasons, the dominant conceptual framework evolved away from the "bud-centered" viewpoint to a "plant-centered" viewpoint that treated the whole plant, consisting of numerous buds, as a unit and considered the entire plant to be the functional equivalent of an animal individual. While this "plant-centered" viewpoint is convenient and great progress has been made using this conceptual framework, some fundamental problems remain logically unsolvable. Previously, I have proposed a new conceptual framework for interpretation of plant morphogenesis, called Plant Morphogenesis 123, which revives a "bud-centered" viewpoint. The perspective of Plant Morphogenesis 123 allows us to address new questions regarding to the mechanisms of plant morphogenesis that are important, and technically accessible, but previously neglected under the "plant-centered" conceptual framework. In addition to describing these questions, I address a more fundamental question for further discussion: why do people study plants?


Fabric phase sorptive extraction combined with high performance liquid chromatography for the determination of favipiravir in human plasma and breast milk.
A fast procedure obtained by the combination of fabric phase extraction (FPSE) with high performance liquid chromatography (HPLC) has been developed and validated for the quantification of favipiravir (FVP) in human plasma and breast milk. A sol-gel polycaprolactone-block-polydimethylsiloxane-block-polycaprolactone (sol-gel PCAP-PDMS-PCAP) coated on 100% cellose cotton fabric was selected as the most efficient membrane for FPSE in human plasma and breast milk samples. HPLC-UV analysis were performed using a RP C18 column under isocratic conditions. Under these optimezed settings, the overall chromatographic analysis time was limited to only 5 min without encountering any observable matrix interferences. Following the method validation procedure, the herein assay shows a linear calibration curve over the range of 0.2-50 µg/mL and 0.5-25 µg/mL for plasma and breast milk, respectively. The method sensitivities in terms of limit of detection (LOD) and limit of quantification (LOQ), validated in both the matrices, have been found to be 0.06 and 0.2 µg/mL for plasma and 0.15 and 0.5 µg/mL for milk, respectively. Intraday and interday precision and trueness, accordingly to the International Guidelines, were validated and were below 3.61% for both the matrices. The herein method was further tested on real samples in order to highlight the applicability and the advantage for therapeutic drug monitoring (TDM) applications. To the best of our knowledge, this is the first validated FPSE-HPLC-UV method in human plasma and breast milk for TDM purposes applied on real samples. The validated method provides fast, simple, cost reduced, and sensitive assay for the direct quantification of favipiravir in real biological matrices, also appliyng a well-known rugged and cheap instrument configuration.


The γH2AX DNA damage assay from a drop of blood.
DNA double-strand breaks (DSB) and blocked replication forks activate the DNA damage response (DDR), a signaling pathway marked by phosphorylation of histone 2AX (H2AX). The phosphorylated form, γH2AX, accumulates at the site of damage and can be detected as foci by immunocytochemistry. Therefore, γH2AX is a sensitive and robust biomarker of DNA damage, notably DSB. Cells from peripheral blood are often used for studies on genotoxic exposure of humans. They are limited, however, by the amount of blood required and the costly blood purification method. Here, we present a method that enables the detection of DNA damage by the analysis of γH2AX foci in a drop of blood. The blood drop method (BDM) is simple, fast, inexpensive and allows large series of blood sampling and storage over time. It can be combined with genotoxic treatment of cells in the collected blood sample for experimental purposes on DNA damage induction and repair. The BDM is suitable for rapid and large-scale screenings of genetic damage in human and animal populations.


Predictors for incidence and remission of NAFLD in the general population during a seven-year prospective follow-up.
Data on the incidence and remission rates of non-alcoholic fatty liver disease (NAFLD) as well as predictive factors are scant. This study aims at evaluating NAFLD's epidemiology in prospective follow-up of individuals sampled from the general population. Evaluation of metabolic parameters and ultrasonographic evidence of NAFLD was performed in 213 subjects, with no known liver disease or history of alcohol abuse. The evaluation was performed at baseline and after a 7-year period by identical protocols. Of the 147 patients who did not have NAFLD at baseline, 28 (19%) were found to have NAFLD at a 7-year follow-up. Baseline BMI, HOMA score, blood cholesterol, triglycerides, leptin levels, and weight gain (5.8±6.1 vs. 1.4±5.5kg, p<0.001) were significantly higher and adiponectin was lower among those who developed NAFLD at 7-year follow-up, compared with those who remained NAFLD-free. However, only weight gain and baseline HOMA were independent predictors for the development of NAFLD. Of the 66 patients who were found to have NAFLD at baseline, as many as 24 patients (36.4%) had no evidence of NAFLD at 7years. Weight loss of 2.7±5.0kg was significantly associated with NAFLD remission. Moreover, there was a 75% remission rate among NAFLD patients who lost 5% or more from their baseline weight. Among the general population, weight gain, and baseline insulin resistance are predictors for NAFLD incidence. One third of NAFLD patients may have remission of disease within a 7-year follow-up, mostly depending on modest weight reduction.


Location of central venous catheters in children by endocavitary ECG: A new technique.
A new technique to establish the position of a central venous catheter (CVC) by endocavitary ECGraphy is described. The principle is based on the fact that the catheter itself may be considered as an electrical conductor by means of its liquid content (saline solution), therefore acting as an exploring electrode. The intrinsic deflection of the P wave shows the proper position of the CVC tip at the sinus node level. The technique has been successfully utilised in 52 children needing antineoplastic chemotherapy and/or total parenteral nutrition, thus avoiding chest X-ray control, which is troublesome and potentially harmful in neonates and infants.


Comparison of phosphatidylinositol-3-kinase signalling within a panel of human colorectal cancer cell lines with mutant or wild-type PIK3CA.
Recent studies have identified conserved missense mutations in PIK3CA, the gene encoding the catalytic phosphatidylinositol-3-kinase subunit p110alpha, in a variety of human cancers. Further investigation demonstrated that PIK3CA mutations lead to increased basal phosphatidylinositol-3-kinase activity, promoting cell growth and invasion [Samuels, Y., Diaz, L.A., Jr., Schmidt-Kittler, O., Cummins, J.M., Delong, L., Cheong, I., Rago, C., Huso, D.L., Lengauer, C., Kinzler, K.W., Vogelstein, B. and Velculescu, V.E. (2005) Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 7, 561-573]. A panel of commonly used colorectal cancer cell lines was screened for these PIK3CA mutations. Constitutive and IGF-1-stimulated phosphatidylinositol-3-kinase activity, signal response and duration were assessed. In the assays used no differences distinguished cells carrying PIK3CA mutations indicating that these mutations did not significantly alter growth factor stimulated or steady state phosphatidylinositol-3-kinase activity in normal cell culture conditions.


Screening for occult malignancy with FDG-PET/CT in patients with unprovoked venous thromboembolism.
Extensive screening strategies to detect occult cancer in patients with unprovoked venous thromboembolism (VTE) are complex and no benefit in terms of survival has been reported. FDG-PET/CT (2-[F-18] fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography), a noninvasive technique for the diagnosis and staging of malignancies, could be useful in this setting. Consecutive patients ≥ 50 years with a first unprovoked VTE episode were prospectively included. Screening with FDG-PET/CT was performed 3-4 weeks after the index event. If positive, appropriate diagnostic work-up was programmed. Clinical follow-up continued for 2 years. Blood samples were collected to assess coagulation biomarkers. FDG-PET/CT was negative in 68/99 patients (68.7%), while suspicious FDG uptake was detected in 31/99 patients (31.3%). Additional diagnostic work-up confirmed a malignancy in 7/31 patients (22.6%), with six of them at early stage. During follow-up, two patients with negative FDG-PET/CT were diagnosed with cancer. Sensitivity (S), positive (PPV) and negative predictive values (NPV) of FDG-PET/CT as single tool for the detection of occult malignancy were 77.8% (95% CI: 0.51-1), 22.6% (95% CI: 0.08-0.37) and 97.1% (95% CI: 0.93-1), respectively. Median tissue factor (TF) activity in patients with occult cancer was 5.38 pM vs. 2.40 pM in those without cancer (p = 0.03). Limitation of FDG-PET/CT screening to patients with TF activity > 2.8 pM would improve the PPV to 37.5% and reduce the costs of a single cancer diagnosis from 20,711€ to 11,670€. FDG-PET/CT is feasible for the screening of occult cancer in patients with unprovoked VTE, showing high S and NPV. The addition of TF activity determination may be useful for patient selection.


Transbilayer diffusion of phospholipids: dependence on headgroup structure and acyl chain length.
The kinetics and thermodynamics of the transmembrane movement (flip-flop) of fluorescent analogs of phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) were investigated to determine the contributions of headgroup composition and acyl chain length to phospholipid flip-flop. The phospholipid derivatives containing n-octanoic, n-decanoic or n-dodecanoic acid in the sn-1 position and 9-(1-pyrenyl)nonanoic acid in the sn-2 position were incorporated at 3 mol% into sonicated single-bilayer vesicles of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC). The kinetics of diffusion of the pyrene-labeled phospholipids from the outer and inner monolayers of the host vesicles to a large pool of POPC acceptor vesicles were monitored by the time-dependent decrease of pyrene excimer fluorescence. The observed kinetics of transfer were biexponential, with a fast component due to the spontaneous transfer of pyrenyl phospholipids in the outer monolayer of labeled vesicles and a slower component due to diffusion of pyrenyl phospholipid from the inner monolayer of the same vesicles. Intervesicular transfer rates decreased approx. 8-fold for every two carbons added to the first acyl chain. Correspondingly, the free energy of activation for transfer increased approx. 1.3 kcal/mol. With the exception of PE, the intervesicular transfer rates for the different headgroups within a homologous series were nearly the same, with the PC derivative being the fastest. Transfer rates for the PE derivatives were 5-to 7-fold slower than the rates observed for PC. Phospholipid flip-flop, in contrast, was strongly dependent on headgroup composition with a smaller dependence on acyl chain length. At pH 7.4, flip-flop rates increased in the order PC less than PG less than PA less than PE, where the rates for PE were at least 10-times greater than those of the homologous PC derivative. Activation energies for flip-flop were large, and ranged from 38 kcal/mol for the longest acyl chain derivative of PC to 25 kcal/mol for the PE derivatives. Titration of the PA headgroup at pH 4.0 produced an approx. 500-fold increase in the flip-flop rate of PA, while the activation energy decreased 10 kcal/mol. Increasing acyl chain length reduced phospholipid flip-flop rates, with the greatest change observed for the PC analogs, which exhibited an approx. 2-fold decrease in flip-flop rate for every two methylene carbons added to the acyl chain at the sn-1 position.(ABSTRACT TRUNCATED AT 400 WORDS)


Genomic organization and the 5' flanking region of the gamma subunit of the human amiloride-sensitive epithelial sodium channel.
The amiloride-sensitive epithelial sodium channel (ENaC) complex is made up of at least three different subunits alpha, beta, and gamma, which are developmentally regulated, selectively expressed, and variously up-regulated by steroid hormones. To understand mechanisms involved in regulation of the gamma subunit, we have determined the structure of the human gammaENaC gene. By 5' rapid amplification of cDNA ends, primer extension analysis, and nuclease protection assay, we identified transcription start sites in human brain, kidney, and lung. A human genomic library was screened and overlapping cosmid clones that span approximately 50 kilobases and contain the hgammaENaC gene were identified. The 5'-untranslated region is 141 bases long, and the translation start codon is contained within the second exon. The human gene spans at least 35 kilobases. The 5' end of the gene including portions of 5' flanking genomic DNA and the first intron are G + C rich and contain several CpG dinucleotides, consistent with a CpG island. The 5' flanking region contains no CCAAT or TATA-like elements but does contain two GC boxes as well as several putative transcription factor binding sites including AP-2, Sp1, CRE, PEA-3, and NF-IL6. This is the first description of the structural organization and the 5' flanking region of a member of the epithelial sodium channel complex.


Optimization of piperidine constructed peptidyl derivatives as proteasome inhibitors.
A series of non-covalent piperidine-containing peptidyl derivatives with various substituents at side chains of different residues were designed, synthesized and evaluated as proteasome inhibitors. After proteasome inhibitory evaluations of all the synthesized target compounds, selected ones were tested for their anti-proliferation activities against three multiple myeloma (MM) cell lines. 8 analogues displayed more potent activities than carfilzomib, and the most promising compound 24 showed IC50 values of 0.8 ± 0.2 nM against 20S proteasome and 8.42 ± 0.74 nM, 7.14 ± 0.52 nM, 14.20 ± 1.08 nM for RPMI 8226, NCI-H929 and MM.1S cell lines, respectively. Additionally, mechanisms of anti-cancer activity of representative compound 24 were further investigated. Apoptosis of RPMI-8226 cells were achieved through accumulating polyubiquitin and inducing the cleavage of caspase and PARP. Besides, half-life in rat plasma of compound 24 was prolonged after optimization, which would be helpful for increasing in vivo activities of this series of derivatives. All the studies confirmed that piperidine-containing non-covalent proteasome inhibitors can be potential leads for anti-MM drug development.


Drug-induced Sweet's syndrome: A case/non-case study in the French pharmacovigilance database.
Sweet's syndrome is an acute febrile neutrophilic dermatosis first described in 1964 by Robert Douglas Sweet. The pathophysiological mechanism is not fully established; however, several cases of Sweet's syndrome have been reported following drug administration. To investigate the existence of pharmacovigilance signals between drugs and the occurrence of Sweet's syndrome, we performed a case/non-case study on reports of 'acute febrile neutrophilic dermatosis' registered in the French pharmacovigilance database. Reporting odds ratio (ROR) with its 95% confidence interval were calculated. Amongthe 994 789 reports recorded in the database, 136 were Sweet's syndrome, of which 50.7% were men and the median age was 59 years (range 15-91). A total of 224 drugs were mentioned as suspects: 21.0% were antibacterials, 19.2% were antineoplastics and 12.1% were immunosuppressants. Median time to onset from drug initiation to the development of Sweet's syndrome was 15 days (range 1-1095). The highest RORs were observed with bortezomib (74.04 [40.8-134.2]), azacitidine (72.14 [29.4-176.9]), perfilgrastim (67.05 [21.2-211.6]), azathioprine (55.46 [34.8-88.4]) and bendamustine (35.84 [11.4-112.8]). Pharmacovigilance signals have been observed between the occurrence of Sweet's syndrome and colony-stimulating factors, immunosuppressants, antineoplastics and antibiotics. Clinicians should be aware of the potential associations with these drugs and should be encouraged to report any case of drug-induced Sweet's syndrome.


Serum apolipoproteins B and A-I and naturally occurring fatty liver in dairy cows.
Serum lipids and apolipoprotein (apo) B and A-I concentrations were determined in 164 dairy cows which had undergone liver biopsy in early lactation. The animals were divided into groups according to fatty liver severity on the basis of hepatic triglyceride content. The serum free fatty acid (FFA) concentration was higher in cows that developed fatty livers than in normal cows, and it correlated highly with liver triglycerides. Serum total cholesterol and triglyceride levels did not correlate with hepatic triglycerides. Both apo B and apo A-I levels were significantly decreased in fatty liver cows. In particular, apo B levels showed a strongly negative correlation with liver triglycerides. The present results suggest that hepatic apolipoprotein synthesis is impeded in fatty liver cows.


Formation, physicochemical and interfacial study of carbamate surfactants.
Carbon dioxide is commonly used as pH regulator in switchable surfactant systems and in the formation of alkyl ammonium-alkyl carbamate ion-pair. Its use to form a meta-stable anionic surfactant has been less explored and can impart a cleavable character to the amphiphile. The reaction between CO2 and an alkylamine, N,N-di(propylamino)dodecylamine (Y12-amine), under alkaline pH conditions, produced a stable anionic carbamate-based surfactant (Y12-carbamate). By heating and exposure to N2, anionic Y12-carbamate could slowly be reverted into Y12-amine. The surface activity of Y12-amine and Y12-carbamate was investigated by surface tension measurements. To study the behavior of Y12-amine at the gas-water interface during CO2 exposure, we used the pendant drop technique with a sealed chamber where the gas composition could be controlled. The Y12-carbamate had a higher CMC than Y12-amine at pH 12, and was also less surface active. The ion pair Y12-ammonium - Y12-carbamate, obtained at neutral pH, exhibited the lowest CMC and the highest surface activity. The interfacial formation of anionic Y12-carbamate induced an increase in surface tension. When CO2 was exchanged to N2, the migration from the bulk to the interface of Y12-amine induced a decrease in surface tension. The rate was dependent on the concentration of Y12-amine.


Contemporary therapy of prolactin-secreting adenomas.
Prolactin-secreting pituitary tumors are common benign pituitary neoplasm that cause amenorrhea, galactorrhea, and infertility. Inhibition of prolactin secretion by a dopamine agonist restores menses and reduces tumor size. This article outlines an approach to therapy and discusses the use of estrogen in women with prolactinomas.


The importance of face-shape masculinity for perceptions of male dominance depends on study design.
Dominance perceptions play an important role in social interactions. Although many researchers have proposed that shape masculinity is an important facial cue for dominance perceptions, evidence for this claim has come almost exclusively from studies that assessed perceptions of experimentally manipulated faces using forced-choice paradigms. Consequently, we investigated the role of masculine shape characteristics in perceptions of men's facial dominance (1) when shape-manipulated stimuli were presented in a forced-choice paradigm and (2) when unmanipulated face images were rated for dominance and shape masculinity was measured from face images. Although we observed large effects of masculinity on dominance perceptions when we used the forced-choice method (Cohen's ds = 2.51 and 3.28), the effect of masculinity on dominance perceptions was considerably smaller when unmanipulated face images were rated and shape masculinity measured from face images (Cohen's ds = 0.44 and 0.62). This pattern was observed when faces were rated separately for physical dominance, social dominance, and masculinity, and was seen for two different sets of stimuli. Collectively, these results suggest that shape masculinity may not be a particularly important cue for dominance perceptions when faces vary simultaneously on multiple dimensions, as is the case during everyday social interactions.


"Madness and Despair are a Force": Global Mental Health, and How People and Cultures Challenge the Hegemony of Western Psychiatry.
The author suggests to consider some important hidden connections in Global Mental Health (GMH) discourse and interventions, above all the political meaning of suffering and symptoms, the power of psychiatric diagnostic categories (both Western and traditional) to name and to occult at once other conflicts, and the implicit criticism expressed by so-called local healing knowledge and its epistemologies. These issues, by emphasizing the importance to explore other ontologies, help to understand the perplexity and resistance that GMH and its agenda meet among many scholars and professionals, who denounce the risks of reproducing and globalizing Western hegemonic values concerning health, illness, and healing.


Metabolism of 2-(2-thienyl)allylamine hydrochloride in the rat: identification of a novel metabolite.
A novel metabolite, 2-(2-thienyl)propionic acid, is formed in vivo from 2-(2-thienyl)allylamine hydrochloride. Mass spectral analysis suggested 2-(2-thienyl)propionic acid formation involves loss of the amine moiety followed by reduction of the olefinic group.


Dietary tryptophan manipulation reveals a central role for serotonin in the anabolic response of appendicular skeleton to physical activity in rats.
Several studies support a serotonin role in the physiological control of bone mass. However, whether serotonin (5-HT) is involved in bone loss due to reduced mechanical stress or unloading is unknown. We investigated the effects of reduced 5-HT tone, induced by tryptophan-free diet, in movement-restraint osteopenia induced by housing mature rats, acclimatised in single cages with a floor area of 1,500 cm(2), in smaller size single cages where their motor activity was reduced. Tryptophan-deficiency significantly worsened movement-restraint-induced bone loss in both femoral metaphysis and diaphysis (DXA analysis) but not at lumbar vertebrae and impaired the mechanical properties of the femur by significantly reducing both cortical thickness and strength strain index (pQCT analysis). Such effects resulted from an impairment of bone turnover with bone resorption exceeding bone formation. Tryptophan-supplemented diet reversed the worsening effects of tryptophan-deficiency on movement-restraint osteopenia. The improvements of both bone mass and strength were associated with an increase of serum osteocalcin and IGF-I, markers of osteoblast activity. In vitro studies in primary cultures of rat osteoblasts suggest that the anabolic action of 5-HT involves the activation of the Wnt/β-catenin pathway. Serotonin significantly increased the cytoplasmatic β-catenin protein levels by the inhibition of the enzyme glycogen synthase kinase-3β, that by phosphorylating β-catenin promotes its degradation. Our data support a role for 5-HT in the anabolic response of the appendicular skeleton to mechanical loading. We suggest that serotonin might stimulate canonical Wnt/β-catenin-dependent bone formation to occur.


Dual-age-class population model to assess radiation dose effects on non-human biota populations.
In the present paper, a two-age-class group, logistic growth model for generic populations of non-human biota is described in order to assess non-stochastic effects of low linear energy-transfer radiation using three endpoints: repairable radiation damage, impairment of reproductive ability and, at higher radiation dose rates, mortality. This model represents mathematically the exchange between two life stages considering fecundity, growth and mortality. Radiation effects are modeled with a built-in self-recovery pool whereupon individuals can repair themselves. In acute effects mode, the repairing pool becomes depleted due to radiation and the model tends to lethality mode. A base calibration of the model's two free parameters is possible assuming that in acute mode 50% of the individuals die on 30 days when a radiation dose equal to the LD(50/30) is applied during that period. The model, which requires 10 species-dependent life-history parameters, was applied to fish and mammals. Its use in the derivation of dose-rate screening values for the protection of non-human biota from the effects of ionizing radiation is demonstrated through several applications. First, results of model testing with radiation effects data for fish populations from the EPIC project show the predictive capability of the model in a practical case. Secondly, the model was further verified with FREDERICA radiation effects data for mice and voles. Then, consolidated predictions for mouse, rabbit, dog and deer were generated for use in a population model comparison made within the IAEA EMRAS II project. Taken together, model predictions suggest that radiation effects are more harmful for larger organisms that generate lower numbers of offspring. For small mammal and fish populations, dose rates that are below 0.02 Gy day(-1) are not fatal; in contrast, for large mammals, chronic exposure at this level is predicted to be harmful. At low exposure rates similar to the ERICA screening dose rate of 2.4 × 10(-4) Gy day(-1), long-term effects on the survivability of populations are negligible, supporting the appropriateness of this value for radiological assessments to wildlife.


Arthroscopic labral repair versus labral debridement in patients with femoroacetabular impingement: a minimum 2.5 year follow-up study.
To compare the clinical results of labral repair with labral debridement in patients undergoing arthroscopy for femoroacetabular impingement. Between July 2008 and December 2011, 67 patients (73 hips) underwent arthroscopic treatment for femoroacetabular impingement. The repair group consisted of 33 patients; 18 hips with pincer only, 1 with CAM only and 15 with combined impingement. The debridement group contained 34 patients; 6 with pincer only, 5 with CAM only and 28 with combined type. The mean age in the repair group was 33.5 years (range, 30-61) and in the debridement group was 39.5 years (range, 18-59 y). At the time of last follow-up, patient's hip function was evaluated with ROM of the hip; daily Hip Outcome scores (dHOS) and Visual Analogue Score (VAS). The mean follow-up was 45.2 month in the repair group and 47.2 month in debridement group. Daily hip outcome scores were significantly improved from preoperatively to last follow-up in both groups (p<0.05). However, there were no statistical significant difference in dHOS between repair and debridement groups (p>0.05) at last follow-up. 2 patients in the repair group and 1 patient in the debridement group had undergone total hip replacement at an average of 16 months (range, 4-32 m) after arthroscopic treatment. Hip joint instability occurred in 1 patient in the repair group due to aggressive capsular resection. This was treated by a periacetabular osteotomy. No difference in hip functional outcomes was observed between labral debridement and labral repair in arthroscopic treatment of femoroacetabular impingement.


A Novel Operative Coaching Program for General Surgery Chief Residents Improves Operative Efficiency.
We evaluated the effect of an operative coaching (OC) model on general surgery chief residents' operative efficiency (OE) measured by operative times. We hypothesized that higher levels of entrustment surgeons intend to offer resident in future similar cases are associated with improved OE. From July 2018 to June 2019, we used a validated instrument to score prospective resident entrustment in 228 evaluations of 6 chief residents during 12 OC sessions each (3 lap colectomy, 3 lap cholecystectomy, 3 ventral hernia, 3 inguinal hernia). Operative times of matched case CPT codes performed by coached chiefs (N = 500) were matched via CPT code to the cases of uncoached chiefs in the academic year 2016-2017 (N = 478). Statistical analysis was performed using Pearson correlation and one-way ANOVA. Prospective entrustment scores from coached chief residents were associated with significantly shorter operative times in matched complex cases (CC) (r = -0.58, p = 0.0047). A similar trend was observed in noncomplex cases (NCC) (r = -0.29, p = 0.18). Compared to the historical cohort, coached chief residents showed a decrease in mean operative time during complex cases (p = 0.0008, d = 0.44), but an increase in mean operative times for noncomplex cases (p < 0.0001, d = 0.33). An OC model improves chief residents' prospective entrustment leading to increased OE in cases with greater levels of operative complexity, showing a decrease in mean operative time compared to uncoached residents in certain procedures. This is the first report showing formal coaching may be a method to enhance chief resident OE.


Clinical and radiological study of sternal fractures in pediatrics.
Sternal fractures are considered uncommon in pediatric patients. Classically, they have been described as fractures secondary to high-energy trauma that have a risk of associated lesions. To describe the clinical and imaging features of sternal fractures in patients less than 18 years of age. We retrospectively reviewed 79 pediatric patients diagnosed with sternal fractures after trauma. We found that 92.4% of the fractures were caused by low-energy trauma and that associated lesions were present in only 3 (4%) patients. Our results suggest that sternal fractures in children are often due to lesser trauma and that associated lesions are rare.


Interaction of Nucleotide Excision Repair Protein XPC-RAD23B with DNA Containing Benzo[a]pyrene-Derived Adduct and Apurinic/Apyrimidinic Site within a Cluster.
The combined action of reactive metabolites of benzo[a]pyrene (B[a]P) and oxidative stress can lead to cluster-type DNA damage that includes both a bulky lesion and an apurinic/apyrimidinic (AP) site, which are repaired by the nucleotide and base excision repair mechanisms - NER and BER, respectively. Interaction of NER protein XPC-RAD23B providing primary damage recognition with DNA duplexes containing a B[a]P-derived residue linked to the exocyclic amino group of a guanine (BPDE-N(2)-dG) in the central position of one strand and AP site in different positions of the other strand was analyzed. It was found that XPC-RAD23B crosslinks to DNA containing (+)-trans-BPDE-N(2)-dG more effectively than to DNA containing cis-isomer, independently of the AP site position in the opposite strand; protein affinity to DNA containing one of the BPDE-N(2)-dG isomers depends on the AP site position in the opposite strand. The influence of XPC-RAD23B on hydrolysis of an AP site clustered with BPDE-N(2)-dG catalyzed by the apurinic/apyrimidinic endonuclease 1 (APE1) was examined. XPC-RAD23B was shown to stimulate the endonuclease and inhibit the 3'-5' exonuclease activity of APE1. These data demonstrate the possibility of cooperation of two proteins belonging to different DNA repair systems in the repair of cluster-type DNA damage.


Predictors of emergency department and outpatient visits for hypoglycemia in type 2 diabetes: an analysis of a large US administrative claims database.
Although hypoglycemia is a well-recognized complication of type 1 diabetes and insulin treatment in type 2 diabetes, less research exists on hypoglycemia in the large number of patients with type 2 diabetes who are treated with oral antidiabetic agents. To identify predictors of hypoglycemia-related emergency department (ED) and outpatient visits in patients with type 2 diabetes. We used the 2004-2008 MarketScan database to conduct a nested case-control analysis. Cohort members were 18 years of age or older with type 2 diabetes and taking an oral antidiabetic agent at cohort entry. We required 12 months or more of continuous enrollment in a noncapitated plan and excluded persons with type 1 or gestational diabetes. Within the cohort, we selected 11,375 cases (first outpatient hypoglycemic event) and 68,247 controls using 6:1 incidence density sampling. A conditional logistic regression model estimated the adjusted odds ratios (AORs) and corresponding 95% confidence intervals of predictors. Cases were more likely than controls to have diabetic complications and other comorbidity, and to be using the most antidiabetic or other medications. The presence of individual micro- and macrovascular complications of diabetes increased the relative rate of hypoglycemia. With no antidiabetic drug therapy as the referent (within 30 days preceding the index date), insulin monotherapy (AOR 1.76; 95% CI 1.50 to 2.05) and insulin in combination with other oral antidiabetic agents (AOR 1.80; 95% CI 1.65 to 1.97) had the highest relative rates of hypoglycemia. Metformin monotherapy (AOR 0.65; 95% CI 0.61 to 0.70), thiazolidinedione monotherapy (AOR 0.71; 95% CI 0.63 to 0.79), and dipeptidyl peptidase-4 inhibitor monotherapy (AOR 0.63; 95% CI 0.45 to 0.89) had decreased relative rates of hypoglycemia. Monotherapy with sulfonylureas, other injectable agents, meglitinides or α-glucosidase inhibitors was not predictive. Medications should be prescribed carefully for patients at high risk of hypoglycemia, particularly those with diabetes complications or those taking insulin alone or in combination. Additional studies are needed to carefully examine the nature of the association between diabetes-related complications and hypoglycemic episodes.


Electric-field-assisted formation of an interfacial double-donor molecule in silicon nano-transistors.
Control of coupling of dopant atoms in silicon nanostructures is a fundamental challenge for dopant-based applications. However, it is difficult to find systems of only a few dopants that can be directly addressed and, therefore, experimental demonstration has not yet been obtained. In this work, we identify pairs of donor atoms in the nano-channel of a silicon field-effect transistor and demonstrate merging of the donor-induced potential wells at the interface by applying vertical electric field. This system can be described as an interfacial double-donor molecule. Single-electron tunneling current is used to probe the modification of the potential well. When merging occurs at the interface, the gate capacitance of the potential well suddenly increases, leading to an abrupt shift of the tunneling current peak to lower gate voltages. This is due to the decrease of the system's charging energy, as confirmed by Coulomb blockade simulations. These results represent the first experimental observation of electric-field-assisted formation of an interfacial double-donor molecule, opening a pathway for designing functional devices using multiple coupled dopant atoms.