Effects of mianserin and fluoxetine on axonal regeneration of brain catecholamine neurons.
The antidepressants, mianserin (MIA) and fluoxetine (FLU), were examined to see if they could induce regeneration of catecholaminergic axons in the rat cerebral cortex. MIA, which has a small or no effect in noradrenaline (NA) reuptake but may enhance release by blocking presynaptic inhibition mediated by alpha 2-adrenoceptors, induced regeneration of catecholamine fibers. In contrast, FLU, a potent reuptake blocker of serotonin was ineffective. This finding suggests that the antidepressant-induced regeneration of cortical catecholamine fibers is associated, at least in part, with enhanced noradrenergic transmission.


Evaluating use of neutral electrolyzed water for cleaning near-patient surfaces.
This study aimed to monitor the microbiological effect of cleaning near-patient sites over a 48-hour period with a novel disinfectant, electrolyzed water. One ward dedicated to acute care of the elderly population in a district general hospital in Scotland. Lockers, left and right cotsides, and overbed tables in 30 bed spaces were screened for aerobic colony count (ACC), methicillin-susceptible Staphylococcus aureus (MSSA), and methicillin-resistant S. aureus (MRSA) before cleaning with electrolyzed water. Sites were rescreened at varying intervals from 1 to 48 hours after cleaning. Microbial growth was quantified as colony-forming units (CFUs) per square centimeter and presence or absence of MSSA and MRSA at each site. The study was repeated 3 times at monthly intervals. There was an early and significant reduction in average ACC (360 sampled sites) from a before-cleaning level of 4.3 to 1.65 CFU/cm(2) at 1 hour after disinfectant cleaning ( P < .0001). Average counts then increased to 3.53 CFU/cm(2) at 24 hours and 3.68 CFU/cm(2) at 48 hours. Total MSSA/MRSA (34 isolates) decreased by 71% at 4 hours after cleaning but then increased to 155% (53 isolates) of precleaning levels at 24 hours. Cleaning with electrolyzed water reduced ACC and staphylococci on surfaces beside patients. ACC remained below precleaning levels at 48 hours, but MSSA/MRSA counts exceeded original levels at 24 hours after cleaning. Although disinfectant cleaning quickly reduces bioburden, additional investigation is required to clarify the reasons for rebound contamination of pathogens at near-patient sites.


T helper cell subsets and related cytokines in infertile women undergoing in vitro fertilization before and after seminal plasma exposure.
In vitro fertilization (IVF) is a well-known method for the treatment of infertility. The present study aimed to compare the differences between infertile women with successful and unsuccessful IVF outcomes regarding the expression of T helper (Th) cell transcription factors and a group of related cytokines before and after exposure to their husbands' seminal plasma. This study was performed on 19 couples with unexplained infertility undergoing IVF treatment. Among the studied group, nine and 10 couples had successful and unsuccessful IVF outcomes, respectively. This study was carried out using real-time polymerase chain reaction. Before seminal plasma exposure, the expression levels of T-bet (p<0.007), interferon-γ (p=0.013), and tumor necrosis factor (TNF)-α (p=0.017) were higher in the infertile women with IVF failure than in those with successful IVF outcomes, while those of GATA3 (p<0.001), Foxp3 (p=0.001), and interleukin (IL)-35 (p<0.003) were lower. After seminal exposure, the expression of T-bet (p=0.02), Rorc (p<0.001), TNF-α (p=0.001), Foxp3 (p=0.02), and interferon-γ (p=0.001) increased in the unsuccessful IVF group, while the expression of Foxp3 (p=0.02), Rorc (p<0.001), IL-23 (p=0.04), IL-17 (p=0.02), IL-6 (p<0.001), transforming growth factor-β (p=0.01), and IL-35 (p<0.001) increased in the successful IVF group. In summary, IVF failure was associated with imbalanced Th1/Th2/Th17/Treg responses. Moreover, our results show that seminal plasma might have a positive effect on IVF outcomes via changes in peripheral blood T cell subsets.


[Therapy of atrial fibrillation].
Atrial fibrillation is the most common cardiac arrhythmia in adults. Paroxysmal atrial fibrillation terminates spontaneously, whereas the persistent form terminates only after medical or electrical cardioversion. Permanent atrial fibrillation cannot be cardioverted. Restoration of sinus rhythm can be achieved by antiarrhythmic drugs or electrical cardioversion, both performed under continuous electrocardiographic monitoring. If atrial fibrillation has lasted longer than 48 hours or the precise time of onset cannot be determined, there are two alternative approaches: systemic anticoagulation to achieve an international normalised ratio (INR) of 2.0 to 3.0 for at least three weeks, followed by cardioversion; or cardioversion guided by transesophageal echocadiography indicating the absence of thrombus. Several drugs have been shown to be effective for the maintenance of sinus rhythm. Anticoagulant therapy is mandatory for a minimum of three weeks after cardioversion. In case of drug refractory, highly symptomatic atrial fibrillation the indication for radiofrequency catheter ablation should be discussed, although the value of this new method is still under evaluation.


Opioid-induced epileptogenic phenomena: anatomical, behavioral, and electroencephalographic features.
Recent animal studies have indicated a possible role of opioids in epilepsy. Intraventricular opioid administration induces a prolonged nonconvulsive stuporous state characterized by epileptiform electroencephalographic patterns, and reversed by naloxone. In high doses, naloxone itself causes generalized clonic convulsions. We compared opioid-induced and naloxone-induced epileptogenic phenomena using quantitative 2-deoxyglucose autoradiography in order to define the anatomical structures involved in these two different seizure types. When opioid-induced seizures occurred, limbic structures were preferentially activated, but when naloxone-induced clonic convulsions occurred, pyramidal and extrapyramidal motor areas and some limbic structures were activated. Based on the present experiments and currently available evidence, we speculate that opioid-mediated epileptogenic phenomena are similar to those occurring during the postictal state of a fully kindled seizure, whereas naloxone-induced epileptogenic phenomena are similar to the ictal state. Therefore, simple pharmacological manipulation of endogenous opioid systems may allow selective study of ictal and postictal phenomena.


Nursing informatics: decades of contribution to health informatics.
In this paper we present a contemporary understanding of "nursing informatics" and relate it to applications in three specific contexts, hospitals, community health, and home dwelling, to illustrate achievements that contribute to the overall schema of health informatics. We identified literature through database searches in MEDLINE, EMBASE, CINAHL, and the Cochrane Library. Database searching was complemented by one author search and hand searches in six relevant journals. The literature review helped in conceptual clarification and elaborate on use that are supported by applications in different settings. Conceptual clarification of nursing data, information and knowledge has been expanded to include wisdom. Information systems and support for nursing practice benefits from conceptual clarification of nursing data, information, knowledge, and wisdom. We introduce three examples of information systems and point out core issues for information integration and practice development. Exploring interplays of data, information, knowledge, and wisdom, nursing informatics takes a practice turn, accommodating to processes of application design and deployment for purposeful use by nurses in different settings. Collaborative efforts will be key to further achievements that support task shifting, mobility, and ubiquitous health care.


MRI of complicated pouchitis.
The purpose of this study is to assess the ability of MRI to identify the presence of inflammation related to the pouch reservoir in symptomatic patients with an ileal pouch-anal anastomosis who present with clinically suspected complicated pouchitis. Initial results suggest that MRI should be considered in patients who have undergone ileal pouch-anal anastomosis and present a clinical impression of complicated pouchitis. MRI showed abnormalities consistent with complicated pouchitis in seven of nine examinations, with findings including pouch wall thickening, abnormal wall enhancement, peripouch fluid collection, sinus and fistula tract formation, lymphadenopathy, and peripouch stranding and fatty proliferation. MRI findings of complicated pouchitis should raise the suspicion of Crohn's disease and should prompt further investigation.


[Necrotizing enterocolitis among preterm newborns with early feeding].
The development of necrotizing enterocolitis is a common and serious risk to newborns. It is caused by splanchnic bed vasoconstriction that can produce intestinal necrosis. The role of onset time, type and, speed enhancements of The factors of enteral feeding related with necrotizing enterocolitis genesis such as feeding onset, type and frequency are not well understood. The incidence of necrotizing enterocolitis and mortality among infants will be compared in infants whose enteral feeding was initiated 48 hours after birth to those whose feeding began on day 5 postpartum. A controlled clinical trial was conducted among 239 newborns weighing between 750-1,500 g and a gestation age of 27-32 weeks of gestational age. The infants were randomly assigned to two groups--135 to an early feeding regime and 104 to delayed feeding. Breast milk or formula milk was used. Feeding was begun with one ml every six hours, progressing to three hour intervals and 20 ml/kg daily. This was increased to 150 ml/kg-d if the infant condition remained stable and it manifested no oral intolerance. In the early feeding group, 14 (10;4 %) necrotizing enterocolitis cases occurred, and in the late feeding group, 9 (8.7 %) occurred (RR= 1.22, 95 % CI 0.49-3.20, p= 0.65). Five children died in early feeding group (3.7 %, 95% CI 1.4-8.9) and eight in late feeding group (7.7 %, 95 % CI 3.6-15.0, RR=0.46, 95 % CI 0.12-1,60, p= 0.18). Early enteral feeding in preterm newborns does not increase the risk of necrotizing enterocolitis or mortality among them; however it represents nutritional advantages for these infants.


A Dynamic Immune Response Shapes COVID-19 Progression.
The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis. We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for 3 to 4 weeks in all three patients. Cytokine analyses of whole blood revealed increased cytokine expression in the single most severe case. However, most inflammatory gene expression peaked after respiratory function nadir, except expression in the IL1 pathway. Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T cell activation that could exacerbate disease or prolong the infection. Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19. This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies.


Bioactive molecules derived from smoke and seaweed Ecklonia maxima showing phytohormone-like activity in Spinacia oleracea L.
Bioactive compounds such as karrikinolide (KAR1 from smoke) and eckol (from the seaweed Ecklonia maxima) show promising effects on several important crop plants. These plant growth-stimulating organic biomolecules, along with crude extracts (smoke-water and Kelpak® product prepared from Ecklonia maxima), were tested on spinach plants. Eckol sprayed at 10-6 M significantly increased all the growth and biochemical parameters examined compared to control spinach plants. All tested plant growth biostimulants significantly increased total chlorophyll, carotenoids and protein content of spinach leaves. The cytokinin profile of spinach plants was also determined. Cis-zeatin, dihydrozeatin and isopentenyladenine types of cytokinins were promoted by both smoke- and seaweed-based biostimulants. In comparison to the control plants, the level of free sinapic acid was greater in all spinach plants treated with these biostimulants. The application of these biostimulants can help spinach crop by improving growth, yield and nutritional quality; moreover, they are organic and cost-effective.


Positron emission tomography instrumentation: an overview.
Positron emission tomography (PET) makes possible the quantitation of the regional distribution of positron-emitting radioisotopes in a selected organ (Ter Pogossian et al.: Radiology 114:89-98, 1975). Since a large variety of physiologic compounds can be labeled with positron emitters (Wolf: Seminars in Nuclear Medicine 11:2-12, 1981; Fowler and Wolf: Nuclear Science Series, 1982), the technique can be used to monitor various biochemical and physiological processes of living tissues (Phelps et al.: Annals of Internal Medicine 98:339-359, 1983; Brodie et al.: Handbook of Neurochemistry, 1983). Indeed, research in the clinical application of PET has expanded considerably over the past 5 years and PET has been used in a variety of clinical problems in psychiatric, neurologic, and oncologic disorders (Phelps and Mazziotta: Science 228:799-809, 1985; Patronas et al.: Journal of Neurosurgery 62:816-822, 1985; Volkow and Tancredi: International Journal of Technology Assessment in Health Care 2:577-594, 1986). Interpretation of the findings by the clinician has sometimes been confounded by the complexity of the technique and the many parameters which can influence the data. A simple knowledge of the methodological background of PET is needed in order to appreciate the potential applications and the limitations of this technique. There are three basic components in PET: instrumentation, radiopharmaceuticals, and mathematical modeling. A number of reviews address varied aspects of the last two components (Fowler and Wolf: Positron Emission Tomography and Autoradiography: Principals and Application of the Brain and Heart, 1986; Karlstrom and Christman: Brookhaven National Laboratory Associated Universities, Inc., 1983; Huang and Phelps: Positron Emission Tomography and Autoradiography: Principles and Applications for the Brain and Heart, 1986), and in this paper we will focus on PET instrumentation as it pertains to its clinical application. The aim of this article is to give an outline of the basic principles behind PET instrumentation, such as positron detection, resolution, quantitation, sensitivity, and image reconstruction as it affects the data presented to the clinician.


Label-free biosensors based on in situ formed and functionalized microwires in microfluidic devices.
Label-free biosensors based on in situ formed and functionalized TTF-Au wires were developed using an integrated microfluidic system. By applying different modification protocols, TTF-Au wires were successfully used for sensitive label-free detection of catecholamines and human IgG by Raman spectroscopy.


Children's consent to treatment: using a scale to assess degree of self-determination.
Discussion and debate regarding decision-making that is 'in the best interest of the child' and that also considers the child's voice in these decisions have increased in recent years. A study was undertaken to identify everyday situations in medical and nursing care in which children had been allowed to have a voice or been denied the right. Twenty-six hospitalized children, ages 6 to 17 years, and 21 parents were interviewed concerning their experiences with hospitalization. The interviews contained examples of 100 situations in which the children could have had a say in decisions concerning their care and treatment. An instrument describing five levels of self-determination was used to analyze the situations. The results showed that there are situations in the daily care of children who are hospitalized where it is possible to discuss the degree of self-determination of the child. To different degrees, staff members honored children's choices in questions concerning their own health.


Modulation of the tissue reninangiotensin-aldosterone system in dogs with chronic mild regurgitation through the mitral valve.
To investigate whether the tissue and plasma renin-angiotensin-aldosterone system (RAAS) is activated in dogs with mild regurgitation through the mitral valve and determine the contribution of chymase and angiotensin-converting enzyme (ACE) to the activation of the RAAS and potential production of angiotensin II during the chronic stage of mild mitral valve regurgitation. 5 Beagles with experimentally induced mild mitral valve regurgitation and 6 clinically normal (control) Beagles. Tissue ACE and chymase-like activities and plasma RAAS were measured and the RAAS evaluated approximately 1,000 days after experimental induction of mitral valve regurgitation in the 5 dogs. Dogs with experimentally induced mitral valve regurgitation did not have clinical signs of the condition, although echocardiography revealed substantial eccentric hyper- trophy. On the basis of these findings, dogs with mitral valve regurgitation were classified as International Small Animal Cardiac Health Council class Ib. Plasma activity of renin and plasma concentrations of angiotensin I, angiotensin II, and aldosterone were not significantly different between dogs with mitral valve regurgitation and clinically normal dogs. Tissue ACE activity was significantly increased and chymase-like activity significantly decreased in dogs with mitral valve regurgitation, compared with values in clinically normal dogs. The tissue RAAS was modulated without changes in the plasma RAAS in dogs with mild mitral valve regurgitation during the chronic stage of the condition. An ACE-dependent pathway may be a major route for production of angiotensin II during this stage of the condition.


Impact of different control policies for COVID-19 outbreak on the air transportation industry: A comparison between China, the U.S. and Singapore.
Many countries have been implementing various control measures with different strictness levels to prevent the coronavirus disease 2019 (COVID-19) from spreading. With the great reduction in human mobility and daily activities, considerable impacts have been imposed on the global air transportation industry. This study applies a hybrid SARIMA-based intervention model to measure the differences in the impacts of different control measures implemented in China, the U.S. and Singapore on air passenger and air freight traffic. To explore the effect of time span for the measures to be in force, two scenarios are invented, namely a long-term intervention and a short-term intervention, and predictions are made till the end of 2020 for all three countries under both scenarios. As a result, predictive patterns of the selected metrics for the three countries are rather different. China is predicted to have the mildest economic impact on the air transportation industry in this year in terms of air passenger revenue and air cargo traffic, provided that the control measures were prompt and effective. The U.S. would suffer from a far-reaching impact on the industry if the same control measures are maintained. More uncertainties are found for Singapore, as it is strongly associated with international travel demands. Suggestions are made for the three countries and the rest of the world on how to seek a balance between the strictness of control measures and the potential long-term industrial losses.


Academia or practice?
Amy Barstow's friends and family always knew she was destined for veterinary medicine. Her aim initially was clinical practice; however, an interest in equine lameness has led her into a PhD in equine biomechanics.


Awareness, trial, and current use of electronic cigarettes in 10 countries: Findings from the ITC project.
In recent years, electronic cigarettes (e-cigarettes) have generated considerable interest and debate on the implications for tobacco control and public health. Although the rapid growth of e-cigarettes is global, at present, little is known about awareness and use. This paper presents self-reported awareness, trial and current use of e-cigarettes in 10 countries surveyed between 2009 and 2013; for six of these countries, we present the first data on e-cigarettes from probability samples of adult smokers. A cross-sectional analysis of probability samples of adult (≥ 18 years) current and former smokers participating in the International Tobacco Control (ITC) surveys from 10 countries. Surveys were administered either via phone, face-to-face interviews, or the web. Survey questions included sociodemographic and smoking-related variables, and questions about e-cigarette awareness, trial and current use. There was considerable cross-country variation by year of data collection and for awareness of e-cigarettes (Netherlands (2013: 88%), Republic of Korea (2010: 79%), United States (2010: 73%), Australia (2013: 66%), Malaysia (2011: 62%), United Kingdom (2010: 54%), Canada (2010: 40%), Brazil (2013: 37%), Mexico (2012: 34%), and China (2009: 31%)), in self-reports of ever having tried e-cigarettes (Australia, (20%), Malaysia (19%), Netherlands (18%), United States (15%), Republic of Korea (11%), United Kingdom (10%), Brazil (8%), Mexico (4%), Canada (4%), and China (2%)), and in current use (Malaysia (14%), Republic of Korea (7%), Australia (7%), United States (6%), United Kingdom (4%), Netherlands (3%), Canada (1%), and China (0.05%)) [corrected]. The cross-country variability in awareness, trial, and current use of e-cigarettes is likely due to a confluence of country-specific market factors, tobacco control policies and regulations (e.g., the legal status of e-cigarettes and nicotine), and the survey timing along the trajectory of e-cigarette awareness and trial/use in each country. These ITC results constitute an important snapshot of an early stage of what appears to be a rapid progression of global e-cigarette use.


Peak-clipping in induction loop systems.
The decision to fit an induction loop system in many buildings is often dictated by cost, in particular that of the amplifier. In order to accommodate the peaks of speech the amplifier must be 4 times as powerful as that required for average speech. This often makes a profound difference to the cost and tips the balance against a loop being installed. Experience with two loops fitted for an audience of hard of hearing people where the peaks were clipped without any apparent loss of discrimination initiated this study. The findings showed that although high fidelity is to be preferred, peak clipping in loop systems can be tolerated without serious loss of intelligibility.


Humeral torsion in the throwing arm of handball players.
Sport-specific upper extremity strain, mostly unilateral, during growth may lead to adaptations in soft tissue and bone. We investigated 51 male professional handball players between 18 and 39 years of age (average, 27 years), 39 right-handed and 12 left-handed. Thirty-eight players had no shoulder problems, and 13 had chronic shoulder pain. Humeral retrotorsion was determined by radiograph. The differences between the throwing and contralateral arms were compared with those of 37 controls who had no history of unilateral strain either through sports or profession. Standard statistical analysis was performed using the t-test. The retrotorsional angle of the humerus in the handball professionals' throwing arm was an average of 9.4 degrees larger in the dominant side than in the nondominant, with a side-to-side difference up to 29 degrees. In the control group, no statistically significant difference was found. In the group without chronic shoulder pain, the side-to-side difference was an average of 14.4 degrees more in the throwing arm than the other side. Players with chronic shoulder pain did not exhibit this increase, even showing an average decrease of humeral retrotorsion of 5.2 degrees in the throwing arm. The humeral retrotorsion increase can be explained as an adaptation to extensive external rotation in throwing practice during growth. Athletes who do not adapt this way seem to have more strain on their anterior capsules at less external rotation and develop chronic shoulder pain because of anterior instability.


Comparison of the effects of bilateral orbital prefrontal cortex lesions and amygdala lesions on emotional responses in rhesus monkeys.
The present study examines the effects of bilateral orbital prefrontal cortex (PFo) lesions on monkeys' emotional responses in two different contexts: in the presence of a rubber snake and in the presence of a human intruder. For comparison, we also assessed the responses of rhesus monkeys with selective amygdala lesions on these same tasks. Monkeys with PFo lesions, like those with amygdala lesions, displayed blunted emotional responses to the fake snake. Unlike monkeys with amygdala lesions, however, monkeys with PFo lesions displayed more mild aggression than controls in the presence of a human intruder. The findings support the idea that the PFo helps integrate sensory signals in the service of choosing among competing responses. In addition, they point to a divergence of the roles of the PFo and amygdala in responding to a social stimulus, the human intruder.


Developmental changes of mast cell populations in the cerebral meninges of the rat.
It is known that both the dura and the pia mater attract and support the differentiation of mast cells. The present study shows that unevenly distributed mast cells in the cerebral meninges of the rat can be found in perivascular sites and vessel ramification points, but can also be unrelated to the meningeal vasculature. It also documents changes in the number, localization and staining preferences of the mast cells in the two meninges of the developing and mature rat brain. Quantitative examination of all types of histochemically differentiated meningeal mast cells reveals no major (although some exist) differences between right and left side subpopulations, but strongly suggests a different origin and fate of the dural and the pial mast cells. The number of dural mast cells, already high from postnatal day 0, although declining from postnatal day 21 onwards, remains conspicuous up to postnatal day 180. In contrast, pial mast cells are comparatively very few in the first day of the postnatal life, and despite a transient significant increase in the following two weeks, they reach almost zero levels from postnatal day 21.


Luminescence and energy transfer properties of Ca2Ba3(PO4)3Cl and Ca2Ba3(PO4)3Cl:A (A = Eu2+/Ce3+/Dy3+/Tb3+) under UV and low-voltage electron beam excitation.
Pure Ca2Ba3(PO4)3Cl and rare earth ion (Eu(2+)/Ce(3+)/Dy(3+)/Tb(3+)) doped Ca2Ba3(PO4)3Cl phosphors with the apatite structure have been prepared via a Pechini-type sol-gel process. X-ray diffraction (XRD) and structure refinement, photoluminescence (PL) spectra, cathodoluminescence (CL) spectra, absolute quantum yield, as well as lifetimes were utilized to characterize samples. Under UV light excitation, the undoped Ca2Ba3(PO4)3Cl sample shows broad band photoluminescence centered near 480 nm after being reduced due to the defect structure. Eu(2+) and Ce(3+) ion doped Ca2Ba3(PO4)3Cl samples also show broad 5d → 4f transitions with cyan and blue colors and higher quantum yields (72% for Ca2Ba3(PO4)3Cl:0.04Eu(2+); 67% for Ca2Ba3(PO4)3Cl:0.016Ce(3+)). For Dy(3+) and Tb(3+) doped Ca2Ba3(PO4)3Cl samples, they give strong line emissions coming from 4f → 4f transitions. Moreover, the Ce(3+) ion can transfer its energy to the Tb(3+) ion in the Ca2Ba3(PO4)3Cl host, and the energy transfer mechanism has been demonstrated to be a resonant type, via a dipole-quadrupole interaction. However, under the low voltage electron beam excitation, Tb(3+) ion doped Ca2Ba3(PO4)3Cl samples present different luminescence properties compared with their PL spectra, which is ascribed to the different excitation mechanism. On the basis of the good PL and CL properties of the Ca2Ba3(PO4)3Cl:A (A = Ce(3+)/Eu(2+)/Tb(3+)/Dy(3+)), Ca2Ba3(PO4)3Cl might be promising for application in solid state lighting and field-emission displays.


Evaluation of Automated Molecular Testing Rollout for Tuberculosis Diagnosis Using Routinely Collected Surveillance Data - Uganda, 2012-2015.
In 2012, Uganda introduced the use of GeneXpert MTB/RIF (Cepheid, Sunnyvale CA), a sensitive, automated, real-time polymerase chain reaction-based platform for tuberculosis (TB) diagnosis, for programmatic use among children, adults with presumptive human immunodeficiency virus (HIV)-associated TB, and symptomatic persons at risk for rifampicin (RIF)-resistant TB. The effect of using the platform's Xpert MTB/RIF assay on TB care and control was assessed using routinely collected programmatic data; in addition, a retrospective review of district quarterly summaries using abstracted TB register data from purposively selected facilities in the capital city of Kampala was conducted. Case notification rates were calculated and nonparametric statistical methods were used for analysis. No statistically significant differences were observed in case notification rates before and after the Xpert MTB/RIF assay became available, although four of 10 districts demonstrated a statistically significant difference in bacteriologically confirmed TB. Once the GeneXpert MTB/RIF platform is established and refined, a more comprehensive evaluation should be conducted.


Caveolin-1-Autophagy Pathway Mediated Cardiomyocyte Hypertrophy Induced by Apelin-13.
Apelin, an endogenous ligand for apelin receptor (APJ), is reported to be involved in cardiomyocyte hypertrophy. In this study, we explored the mechanism of cardiomyocyte hypertrophy induced by apelin-13/APJ system. Left ventricular hypertrophy (LVH) rat model was established by constricting the abdominal aorta. Western blots were used for protein expression in LVH rats and cultured H9c2 cardiomyocytes. Transmission electron microscopy (TEM) was used to monitor morphological features of cells. In addition, the diameter and volume of H9c2 cells were detected by Scepter™ Handheld Automated Cell Counter. We found that the APJ was increased, but caveolin-1 was decreased in heart of LVH rats. In addition, caveolin-1 was suppressed by apelin-13, and this effect was reversed by APJ antagonist F13A in cultured H9c2 cardiomyocytes. Apelin-13 not only stimulated the formation of autophagolysosomes, autophagosome, and lysosomes but also increased the expression of autophagic markers Beclin-1 and LC3II/I. Besides, the increase of Beclin-1 and LC3 II/I was reversed by F13A or caveolin-1 overexpression and further enhanced by caveolin inhibitor. Furthermore, the cardiomyocyte hypertrophy index brain natriuretic peptide (BNP) induced by apelin-13 was blunt by F13A or autophagy inhibitor 3-methyladenine and further promoted by caveolin inhibitor. And caveolin-1 overexpression reduced the diameter and volume of H9c2 cells induced by apelin-13. Our study indicates that caveolin-1-autophagy pathway mediated cardiomyocyte hypertrophy induced by apelin-13/APJ system, which might provide a novel therapeutic target for cardiac hypertrophy disease.


A case of oculo-auriculo-vertebral spectrum with long-term and comprehensive management.
To show that a patient with severe oculo-auriculo-vertebral spectrum can achieve satisfactory occlusion and facial appearance through long-term and comprehensive management. A patient, with oculo-auriculo-vertebral spectrum, had bilateral cleft lip and palate, macrostomia, malformed pinna, and unilateral hypoplasia of the zygomatic arch and mandible, which resulted in an asymmetric facial appearance characteristic of hemifacial microsomia. After bilateral lip repair and palatal closure, surgical repair of the pinna, nose, and cheiloplasty was performed. The patient was seen at the authors' dental hospital at 12 years 2 months of age. After lateral expansion of the maxillary arch, an edgewise multibracket appliance was placed and presurgical orthodontic treatment was begun. Combined maxillary and mandibular osteotomies were performed when the patient was 19 years of age, followed by genioplasty, multiple repair of the mandibular body and lip, and soft tissue transplantation to the left cheek, to improve facial symmetry. After prosthetic treatment at 23 years of age, a stable and functional occlusion with a satisfactory facial appearance was achieved.


Transcatheter edge-to-edge repair of the tricuspid valve: The US experience.
To examine the trends in utilization and outcomes of tricuspid valve (TV) transcatheter edge-to-edge repair (TEER). Surgery for isolated tricuspid regurgitation is associated with high morbidity and mortality and is rarely performed. TV TEER is an attractive alternative. The Nationwide Readmissions Database was queried using the International Classification of Diseases, 10th Revision, procedure code for TV TEER for years 2016-2019. The main outcomes were trends in utilization and in-hospital all-cause mortality. We identified 918 hospitalizations for TV TEER. There was an uptrend in its utilization from 13 cases in the first quarter of 2016 to 122 cases in the last quarter of 2019 (p trend < 0.001). Concomitant mitral valve (MV) TEER was performed in 42.1% of admissions. The overall in-hospital mortality was 2.1%. Surgical TV replacement was needed in 1.1% of admissions; none of them died during the index hospitalization. Unplanned rehospitalizations were common at 30 days (15.7%); 38.2% of those were due to heart failure. There was no difference in in-hospital mortality between isolated TV TEER and combined MV and TV TEER (1.7% vs. 2.6%, p = 0.359). However, admissions receiving combined procedure had lower length of stay and urgent readmission rate. The current study showed that there was an increase in the utilization of TV TEER over 2016-2019 in the United States. TV TEER was associated with low rates of in-hospital mortality; however, the rate of urgent readmission remains high, mainly due to heart failure.


Better synchronizability in generalized adaptive networks.
In this paper, to study the interaction between network structure and dynamical property in the context of synchronization, a previously proposed adaptive coupling method is generalized where the coupling strength of a node from its neighbors not only develops adaptively according to the local synchronization property between the node and its neighbors (dynamical part) but also is modulated by its local structure, degree of the node with the form 1/k(i)(alpha) (topological part). We can show both numerically and analytically that the input coupling strength of the network after adaptation displays a power-law dependence on the degree, k(-theta), where the exponent theta is controlled by alpha as theta=(1+alpha)/2. Compared to the original adaptive coupling method, after the addition of modulation, the distribution of the node's intensity is tunable and can be more homogenous with alpha approximately 1, which results in better synchronizability. It is also found that the synchronization time can shrink greatly. Our theoretical work in the context of synchronization provides not only a deeper understanding of the interplay between structure and dynamics in real world systems, such as opinion formation and concensus, but also potential approaches to manipulate the global collective dynamics through local adaptive control.


The costs of caring for erectile dysfunction in a managed care setting: evidence from a large national claims database.
We examined the direct costs of erectile dysfunction (ED) empirically. A naturalistic cohort study was done in 285,436 patients with ED and 51 health plans that covered 28 million lives nationwide from 1999 through 2001. Based on claims that had an ED related diagnosis code, procedure code or medication code we categorized the cost structure of ED care and calculated the annual costs of ED care per patient with ED, per user and per member monthly for individual and for all categories of ED care. A patient with ED in a health plan spent about an average of 83.91 dollars in 1999, 95.41 dollars in 2000 and 119.26 dollars in 2001 for ED care. In 2001, 37.08% of ED care costs per patient with ED were spent on phosphodiesterase type 5 (PDE-5) inhibitor therapy, 14.36% were spent on physician office visits, 10.19% were spent on diagnosis procedures, 8.45% were spent on testosterone hormone therapy, 3.85% were spent on penile prosthesis implantation, 4.41% were spent on intracavernous injection, 2.68% were spent on alprostadil pellet insertion and 0.81% was spent on vacuum erection devices. Of the 7 commonly used ED treatments PDE-5 inhibitor therapy has the lowest annual cost per user. In 2001 ED imposed a 122,669 dollars annual burden to a health plan with 100,000 members, that is or 0.108 dollars per member monthly. Each patient with ED spent 119.26 dollars annually for all ED related services or treatments. Of the 7 commonly used treatments PDE-5 inhibitor therapy had the lowest annual cost per user.


Expression of vascular endothelial growth factor and HER2/neu in stage II colon cancer and correlation with survival.
Monoclonal antibody-directed therapy has been used as an effective treatment for some cancers that overexpress HER2/neu and vascular endothelial growth factor (VEGF). Overexpression of the HER2/neu oncogene and VEGF has been reported to occur in adenocarcinomas of the colon. Assessing whether HER2/neu and VEGF overexpression could serve as prognostic indicators for stage II colon cancer may provide insight into optimal treatment following surgery. Demographic and tumor characteristics from 109 patients diagnosed with stage II colon cancer between 1991 and 1996 were assessed for HER2/neu and VEGF expression using immunohistochemical staining techniques. Of the 109 cases, 107 (98%) were histologically classified as adenocarcinomas, 105 (96%) were grades 2/3, and 105 (96%) were stage T3. Only 12 cases (11%) exhibited HER2/neu overexpression and 72 cases (66%) exhibited VEGF expression. There was no significant difference in overall survival or in time to recurrence between the groups with and without HER2/neu overexpression. There was a trend toward decreased overall survival with VEGF expression (P = 0.07), but no difference in time to recurrence (P = 0.63). There were 18 patients who received adjuvant chemotherapy, but removal of these patients from the analysis did not change the results. There was no association between HER2/neu and VEGF expression and patient demographics or tumor characteristics, with the exception of VEGF expression and mucinous histology (P < 0.01). Our results do not support an association between HER2/neu or VEGF expression and overall survival or time to recurrence in stage II colon cancer. With further investigation, a significant correlation may be found between VEGF expression and prognosis, and thus direct therapy with a monoclonal antibody.


Fabrication of Bioengineered Skin by Injection Molding: A Feasibility Study on Automation.
The use of bioengineered skin has facilitated fundamental and applied research because it enables the investigation of complex interactions between various cell types as well as the extracellular matrix. The predominantly manual fabrication of these living tissues means, however, that their quality, standardization, and production volume are extremely dependent on the technician's experience. Simple laboratory automation could facilitate the use of living tissues by a greater number of research groups. We developed and present here an injection molding technique for the fabrication of bilayered skin equivalents. The tissue was formed automatically by two separate injections into a customized mold to produce the dermal and epidermal skin layers. We demonstrated the biocompatibility of this fabrication process and confirmed the resulting bilayered morphology of the bioengineered skin using histology and immunohistochemistry. Our findings highlight the possibility of fabricating multilayered living tissue by injection molding, suggesting that further investigation into this automation method could result in the rapid and low-cost fabrication of standardized bioengineered skin.


Synchrony and rhythm interaction: from the brain to behavioural ecology.
This theme issue assembles current studies that ask how and why precise synchronization and related forms of rhythm interaction are expressed in a wide range of behaviour. The studies cover human activity, with an emphasis on music, and social behaviour, reproduction and communication in non-human animals. In most cases, the temporally aligned rhythms have short-from several seconds down to a fraction of a second-periods and are regulated by central nervous system pacemakers, but interactions involving rhythms that are 24 h or longer and originate in biological clocks also occur. Across this spectrum of activities, species and time scales, empirical work and modelling suggest that synchrony arises from a limited number of coupled-oscillator mechanisms with which individuals mutually entrain. Phylogenetic distribution of these common mechanisms points towards convergent evolution. Studies of animal communication indicate that many synchronous interactions between the signals of neighbouring individuals are specifically favoured by selection. However, synchronous displays are often emergent properties of entrainment between signalling individuals, and in some situations, the very signallers who produce a display might not gain any benefit from the collective timing of their production. This article is part of the theme issue 'Synchrony and rhythm interaction: from the brain to behavioural ecology'.


Biology of SLAC1-type anion channels - from nutrient uptake to stomatal closure.
Contents 46 I. 46 II. 47 III. 50 IV. 53 V. 56 VI. 57 58 58 References 58 SUMMARY: Stomatal guard cells control leaf CO2 intake and concomitant water loss to the atmosphere. When photosynthetic CO2 assimilation is limited and the ratio of CO2 intake to transpiration becomes suboptimal, guard cells, sensing the rise in CO2 concentration in the substomatal cavity, deflate and the stomata close. Screens for mutants that do not close in response to experimentally imposed high CO2 atmospheres identified the guard cell-expressed Slowly activating anion channel, SLAC1, as the key player in the regulation of stomatal closure. SLAC1 evolved, though, before the emergence of guard cells. In Arabidopsis, SLAC1 is the founder member of a family of anion channels, which comprises four homologues. SLAC1 and SLAH3 mediate chloride and nitrate transport in guard cells, while SLAH1, SLAH2 and SLAH3 are engaged in root nitrate and chloride acquisition, and anion translocation to the shoot. The signal transduction pathways involved in CO2 , water stress and nutrient-sensing activate SLAC/SLAH via distinct protein kinase/phosphatase pairs. In this review, we discuss the role that SLAC/SLAH channels play in guard cell closure, on the one hand, and in the root-shoot continuum on the other, along with the molecular basis of the channels' anion selectivity and gating.


COVID-19 and Stressful Adjustment to Work: A Long-Term Prospective Study About Homeworking for Bank Employees in Italy.
The COVID-19 evolution has forced the massive introduction of homeworking (HW) for most employees in the initial stages of the pandemic and then return to work, mainly due to the vaccination campaign. These multiple abrupt adjustment demands in work may be a source of intense stress for office workers with consequences on wellbeing and the quality of life. This long-term prospective study aimed at investigating the effect of adaptation demands on a broad population of employees of a large Italian banking group in the job-related stress framework. We administered a web-based survey to 1,264 participants in Reopening after the first lockdown, from June to October 2020, at 841 subjects in Second Wave, corresponding to the rise of contagions from November 2020 to January 2021, and to 491 individuals in Vaccination Round, which ranged from February to June 2021. We assessed workaholism by using the Dutch Work Addiction Scale (DUWAS-10), work-family conflicting overlap by using the Work and Family Conflict Scale (WAFCS), and concern for back to work (BW) and for HW by specific questions. Higher WAFCS scores characterized Reopening and Vaccination Round while Second Wave had the highest level of concern for HW. Women and younger individuals showed the highest concern for BW, WAFCS, and DUWAS-10 scores regardless of the pandemic stage. HW days per week were related to more heightened concern for BW and lower concern for HW, DUWAS, and WAFCS scores. The number of children was related to lower Concern for BW and higher WAFCS scores in Reopening and Second Wave. Our data showed that massive adjustment demands in work and family routine represented a significant source of stress for employees, regardless of the different pandemic stages. The highest level of fatigue emerged in women and younger subjects. These results shed light on the need for a road map to promote a gradual and structured adjustment for workers and encourage organizations to consider homeworking as a valid stable alternative.


Congenital melanotic macules of the tongue. A case report and brief review of the literature.
Congenital melanotic macules of the tongue (CMMT) are a rare and benign condition that is probably underestimated. We report the case of an African infant with multiple congenital hyperpigmented macules of the tongue. To avoid a difficult-to-perform procedure such as a tongue biopsy, focused clinical monitoring was performed every 3 months for 30 months to detect significant changes. A clinical diagnosis of CMMT was made in the absence of concomitant systemic diseases using the clinical findings, the location on the tongue, the negative family history for melanoma, and the absence of drugs and toxic exposure. Clinical follow-up may be sufficient to monitor CMMT rather than performing a tongue biopsy.


Rapid reduction of severe hypertension with minoxidil.
Five patients presenting with severe hypertension who failed to exhibit diastolic blood pressures less than 120 mm Hg following the oral administration of propranolol (60--80 mg) and furosemide (40 mg) received minoxidil (20 mg, p.o.). Systemic blood pressure, heart rate, and cardiac output were measured prior to and hourly following the addition of minoxidil to the regimen of propranolol and furosemide. One hour following the addition of minoxidil, systemic blood pressure decreased from 204/126 to 186/114 mm Hg (mean systolic/mean diastolic blood pressure). Four hours after minoxidil administration, systemic blood pressure was 175/105 mm Hg. Four of the 5 subjects exhibited diastolic blood pressures greater than 100 mm Hg at 4 hr and were given a booster dose of minoxidil (5--20 mg). Systemic blood pressure subsequently decreased to 153/92 mm Hg at 8 hr and to 142/86 mm Hg at 12 hr following the initial dose of minoxidil. The reduction of systemic blood pressure was achieved without significant change in heart rate or cardiac output. These data indicate that stepped-care therapy utilizing a diuretic, a beta-blocking agent, and minoxidil produces prompt, significant, and sustained reduction of systemic blood pressure in patients with severe, potentially life-threatening hypertension.


Grain boundary sliding in pure and segregated bicrystals: a molecular dynamics and first principles study.
Sliding behaviors of Σ9(221) grain boundary bicrystals have been investigated in pure metals (Al, Ag, Au, Cu, Pt and Co) and in segregated metals (Cu segregated by Al, Ag, Au, Pt and Co) by molecular dynamics simulations and first-principles calculations. The grain boundary energy, the atomic size and the electronegativity of the segregated elements were not critical for the occurrence of grain boundary sliding. On the other hand, the sliding rate increased as the minimum charge density decreased at the bond critical point. This was the case for both pure grain boundary models and segregated grain boundary models. Therefore, it seems that the sliding rate depends on atomic movement at sites with minimum charge density, irrespective of the elements involved and of the presence of segregated atoms.


The Effects of Curcumin Supplementation on Metabolic Biomarkers and Body Mass Index in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Curcumin is one of the most commonly used indigenous molecules endowed with various shielding functionalities that protect the liver. In the present research, we aimed to investigate the effects of curcumin on metabolic factors and body mass index (BMI) in patients with non-alcoholic fatty liver disease (NAFLD) using a meta-analysis of randomized, controlled trials. Online databases PubMed, Embase, Web of Science, and Science Direct were searched until April 2021 to identify eligible articles. Fourteen trials were included. The results showed that curcumin consumption can significantly reduce AST (-0.35, (-0.57 to -0.14)), total cholesterol (-0.81, (-1.34 to -0.27)), TG (-0.49, (-0.71 to -0.27)), and FBS (-0.28, (-0.46 to -0.09)) in patients with NAFLD. However, the improvements in ALT (-0.29, (-0.58 to 0.00)), LDL (-0.48, (-0.97 to 0.01)), HDL (0.03, (-0.38 to 0.44)), and BMI (-0.13, (-0.29 to 0.02)) were not statistically significant. Furthermore, the findings revealed that the optimal dose and duration of curcumin consumption for patients with NAFLD is <500 mg/d for less than 10 weeks. The present study suggests that consuming curcumin can improve liver enzymes, lipid profile, FBS, and BMI in patients with NAFLD. Moreover, curcumin supplementation may provide beneficial effects on metabolic biomarkers and body weight if used at the appropriate dose and duration. Further RCTs are required to confirm our findings.


A preliminary study on the role of the equine guttural pouches in selective brain cooling.
The equine guttural pouch is a large, air-filled diverticulum of the auditory tube whose function is not clear. Since the horse does not possess a known, well-developed brain-cooling mechanism that could satisfy cerebral thermoregulatory demands, an hypothesis is proposed that respiratory air enters the guttural pouches, when needed, to ventilate and cool the internal carotid arteries (ICA). Experiments were initially carried out on nine cadavers, where blood flow was mimicked with warmed saline propelled by peristaltic pumps. Subsequent experiments were conducted on an anaesthetized horse where the guttural pouch was ventilated and ICA temperatures were measured. Results showed that whenever the guttural pouch was ventilated with cooled or warmed environmental air, or warmed 100% humidified air, temperatures within the ICA dropped significantly in cadavers (0.4-5 degrees C) and in the anaesthetized horse (1-3 degrees C), depending on conditions. Simulated respiration trials also resulted in ICA temperature drops of 0.9-2.3 degrees C in two of five cadavers tested, indicating that the wide 3-5 cm pharyngeal orifices of the guttural pouches have the capacity to allow enough respiratory air to ventilate the pouch. Despite the fact that a single, unbranching 13 cm portion of the ICA is exposed on the wall of each guttural pouch, the results of this investigation suggest that during heavy exercise, horses could utilize their guttural pouches to cool ICA blood destined for the brain.


Ultramorphometric studies of the adrenal cortex of adult rats after neonatal administration of sex steroids.
The outer zona fasciculata of 28 Sprague-Dawley rats, 8 weeks old, was studied by means of ultramorphometry. Four males and 4 females each received 1250 mug of testosterone proprionate (TP) or 300 mug oestradiol benzoate (OeB) on the second day of life. Four males and 4 females in oestrus or dioestrus served as controls. The controls showed both sex and cyclic differences: in comparison to the males, females displayed a finely dispersed lipoid pattern; enlargement of the nucleus and an increase in the amount of smooth endoplasmic reticulum (SER) indicated an increased stimulation of the cortex during oestrus. Neonatal administration of TP in females causes a distinct enlargement of cells with an increase in the volumes of nucleus, mitochondria, liposomes, SER and liposomes. The mitochondria and liposomes show a small-dispersed pattern of distribution. All these function-specific morphometric parameters point to an increased activity of the individual cell. The changes are less pronounced after OeB than after TP. In the male, neonatal administration of sex steroids results in an alteration of the sizes of the mitochondria and liposomes. The liposomes are distributed finely dispersed. At the same time there is an increase in the lipoid content. According to these parameters, fasciculata cells fulfil the morphological conditions that are a prerequisite for an elevated functional reaction. This change is more marked following OeB than TP. Sex dimorphism is preserved following neonatal application of sex steroids since the alterations are much more pronounced in females than in males.


Effects of ospemifene on vaginal epithelium of post-menopausal women.
Ospemifene is a selective estrogen receptor modulator used for the treatment of vulvo-vaginal atrophy (VVA) in post-menopausal women. No direct evidence of its effects on histological features of the human vagina has been reported. To evaluate the effects of ospemifene on histological parameters, glycogen content, proliferation, and estrogen receptor α expression (ERα) of vaginal epithelium in post-menopausal women. Thirty-two post-menopausal women undergoing surgical procedures were enrolled. Sixteen subjects taking ospemifene at the time of inclusion (OSP) were compared to 16 subjects not taking any hormone (CTL). Vaginal biopsies were taken from the proximal and distal vaginal wall during surgery to evaluate histology, Ki-67 and ERα expression. OSP group showed thicker vaginal epithelium (349 ± 64 vs. 245 ± 53 μm, p < .001), higher proliferation index (212 ± 47 vs. 127 ± 28 Ki-67+ cells/mm, p < .001), higher epithelial (27.3 ± 3.1 vs. 20.6 ± 2.9 score, p < .001) and stromal (26.6 ± 4.9 vs. 20.6 ± 2.6 score, p < .001) ERα expression when compared to the CTL group. In postmenopausal women affected by VVA, 1 month intake of ospemifene is associated with an increased maturation, and ERα expression of the vaginal mucosa. These changes may partially explain the improvement of symptoms of vaginal atrophy reported with this drug.


Serum dioxin levels in former New Zealand sawmill workers twenty years after exposure to pentachlorophenol (PCP) ceased.
From the 1950s to the late 1980s pentachlorophenol (PCP) based anti-sapstain fungicides were widely used in the New Zealand timber industry. Workers involved in treatment, or those handling freshly treated timber, experienced significant PCP exposure. Commercial grade PCP contained contaminants including 2,3,7,8-substituted polychlorinated dibenzo-p-dioxin (PCDD) and dibenzofuran (PCDF) congeners. To determine whether PCP exposure had resulted in elevated serum dioxin levels twenty years after its use had ceased we tested 94 former sawmill workers randomly selected from surviving members of a cohort enumerated for a mortality and cancer incidence study. After interviewing these individuals to collect demographic data and a comprehensive work history, they were divided into 71 PCP-exposed and 23 non-exposed individuals on the basis of job title and work tasks performed. We compared age-adjusted dioxin levels in the exposed and non-exposed groups, examined the effect of PCP exposure duration and intensity, and compared congener profiles with those found in the commercial grade PCP used at the time. Mean levels in exposed workers were elevated when compared with the non-exposed, with levels of 1,2,3,6,7,8-HxCDD, 1,2,3,4,6,7,8-HpCDD and OCDD being two to three times higher. The congener profiles in serum were consistent with those in PCP solutions, and dioxin levels increased with both employment duration and estimated exposure intensity. Serum dioxin levels in former New Zealand sawmill workers remain elevated twenty years after exposure to PCP ceased, and reflect the pattern of past PCP exposure.


What Adult Electrocardiogram (ECG) Diagnoses or Findings are Most Important for Advanced Care Paramedics to Know?
The interpretation of electrocardiograms (ECGs) is an essential competency in modern paramedicine. Although educational guidelines for paramedic ECG interpretation exist, they are broad, not evidence-based, and lack prioritization in a prehospital clinical context. We conducted this study to gain consensus among stakeholders (EMS physicians, paramedic educators, and paramedic clinicians) regarding which ECG diagnoses or findings are most important for a practising advanced care paramedic to know. Methods: This study was an internet-based Delphi survey. We purposefully sampled participants in pairs (physician/paramedic) from all 10 Canadian provinces. Individuals rated a previously developed comprehensive list of emergency ECG diagnoses or findings on the importance of paramedic recognition and impact on prehospital care using a 4-point Likert scale. The consensus was achieved with a minimum of 75% agreement on Likert rating for a single diagnosis or finding during survey rounds one to three. When consensus was not reached, stability was defined as a shift of individual ratings between rounds of 20% or less. All 20 participants completed the first and second rounds of the survey, and 17 (85%) completed three rounds. Overall, 32 (26.4%) of 121 potentially important ECG diagnoses or findings reached consensus, 2 (1.7%) reached stability and 87 (71.9%) reached neither consensus nor stability. Twenty-one (17.4%) diagnoses or findings were considered "Very Important", six (4.9%) "Important", and five (4.1%) "Minimally Important". In the first round of the survey, the mean rating of the importance of a paramedic knowing a specific ECG diagnosis or finding was lower in the physician group than the paramedic group on 85 (72%) of 118 initial diagnoses or findings. We have created a list of ECG diagnoses or findings prioritized for the prehospital context that may assist paramedic educators in focusing on educational interventions. Many ECG diagnoses or findings failed to reach consensus or stability, demonstrating potential disagreement regarding clinical expectations for ECG knowledge among paramedics or physicians.


NS1 Antigen Capture ELISA an Effective Method for Diagnosis of Early Dengue Infection - Report of an Outbreak at Angul District, Odisha, India.
An outbreak of dengue infection occurred in Angul district of Odisha in the month of August & September, 2011. The study was undertaken to detect NS1 antigen positivity among the study population, to compare IgM capture ELISA with NS1 antigen detection for diagnosis of dengue and to identify the predominant genotype of Dengue virus responsible for the outbreak. Total 1020 serum samples were collected from clinically suspected cases of dengue from the outbreak. All were subjected for NS1 antigen detection, 92 were selected based on their clinical severity of illness (fever, rash, bleeding manifestation, arthralgia) for further study of IgM ELISA and platelet count and 148 NS1 positive samples were selected from different Blocks of Anugul district for RT-PCR at NIV, Pune, India. Five hundred and thirteen (50.2%) samples were positive for NS1 antigen (highly significant p-value <0.0001, C.I - 95%) with 88% positivity during 1-5 days. The NS1 Ag positivity was peaked to 86.9% on days 3 to 5 (Sensitivity & NPV - 100% each) & declined to 6.2% during 6-10 days with a low sensitivity of 7.14% but 100% specificity & PPV. However, the IgM antibody positivity was 81.2% on days 6 to 10 and 87.5% after 10 days (Sensitivity- 100%, Specificity-13.33%,PPV-7.14% & NPV - 100%). RT-PCR resulted 32.4% positivity (6- DEN1, 39 - DEN 2 & 3- DEN 3) among which 20% were in IgM +ve & 68% in IgM -ve cases. Therefore, early diagnosis of dengue could be mainly by NS1 antigen detection whereas Ig M ELISA is a better tool during the later stage of infection &RT-PCR is more effective in IgM -ve cases.The predominant genotype responsible for the outbreak was found to be DEN-2.


Role of intratubular pressure during the ischemic phase in acute kidney injury.
Acute kidney injury (AKI) induced by clamping of renal vein or pedicle is more severe than clamping of artery, but the mechanism has not been clarified. In the present study, we tested our hypothesis that increased proximal tubular pressure (Pt) during the ischemic phase exacerbates kidney injury and promotes the development of AKI. We induced AKI by bilateral clamping of renal arteries, pedicles, or veins for 18 min at 37°C, respectively. Pt during the ischemic phase was measured with micropuncture. We found that higher Pt was associated with more severe AKI. To determine the role of Pt during the ischemic phase on the development of AKI, we adjusted the Pt by altering renal artery pressure. We induced AKI by bilateral clamping of renal veins, and the Pt was changed by adjusting the renal artery pressure during the ischemic phase by constriction of aorta and mesenteric artery. When we decreased renal artery pressure from 85 ± 5 to 65 ± 8 mmHg, Pt decreased from 53.3 ± 2.7 to 44.7 ± 2.0 mmHg. Plasma creatinine decreased from 2.48 ± 0.23 to 1.91 ± 0.21 mg/dl at 24 h after renal ischemia. When we raised renal artery pressure to 103 ± 7 mmHg, Pt increased to 67.2 ± 5.1 mmHg. Plasma creatinine elevated to 3.17 ± 0.14 mg·dl·24 h after renal ischemia. Changes in KIM-1, NGAL, and histology were in the similar pattern as plasma creatinine. In summary, we found that higher Pt during the ischemic phase promoted the development of AKI, while lower Pt protected from kidney injury. Pt may be a potential target for treatment of AKI.


Formation of the biopulsatile vascular pump by cardiomyocyte transplants circumvallating the abdominal aorta.
In spite of the fact that patients with heart diseases requiring heart transplantation are increasing in the world, there are a lack of donors, which makes it hard to offer them these life-saving transplants. As a way to overcome this dilemma, we have researched the addition of the new biopump, which consists of the cultured embryonic cardiomyocytes grafted around the abdominal aorta and contracts spontaneously, which subsequently supports the function of the host heart. Ventricular tissues from ICR 14-day-old embryos were cultured and were injected to BALB/c nude mice (male, 8-week-old) subperitoneally around the abdominal aorta. At 3 and 7 days after implantation, action potential of the grafts was measured. Grafts were prepared for histological study. The grafts survived, showed vigorous angiogenesis, and contracted spontaneously. The cardiomyocytes in the grafts showed irregular arrangement, containing myofibrils with sarcomeres and intercalated disks. It was confirmed by immunohistochemistry that the cardiomyocytes in the grafts matured in accordance with normal development. The grafts were very quickly invaded by small vessels from the surrounding tissues showing the formation of new circulation. Embryonic cardiomyocytes have the ability to remodel the abdominal aorta into a spontaneous pulsating apparatus and to function as a vascular pump.


Effective Delivery of Nef-MPER-V3 Fusion Protein Using LDP12 Cell Penetrating Peptide for Development of Preventive/Therapeutic HIV-1 Vaccine.
There is no effective and safe preventive/therapeutics vaccine against HIV-1 worldwide. Different viral proteins such as Nef, and two regions of Env including; variable loop of gp120 (V3) and membrane proximal external region of gp41 (MPER) are particularly important for vaccine development in different strategies and they are also the primary targets of cellular and humoral immune responses. On the other side, LDP12 is a new cell-penetrating peptide (CPP) which is capable of therapeutic application and cargoes delivery across the cellular membrane. In current study, we designed and produced Nef-MPER-V3 fusion protein harboring LDP12 that has the capability of being used in future vaccine studies. The CPP-protein was expressed in E. coli Rosseta (DE3) strain and purified through Ni-NTA column. Characterization of cellular delivery and toxicity of the recombinant protein were evaluated by western blotting and MTT assay. Our results showed that the CPP-protein was successfully expressed and purified with high yield of 5 mg/L. Furthermore, non-cytotoxic effect was observed and specific band (~ 37 KDa) in western blotting indicated the capability of LDP12 to improve the rate of penetration into HEK-293T cells in comparison with a control sample. Altogether, the data indicated that LDP12 CPP could be utilized to internalize HIV-1 Nef-MPER-V3 protein into eukaryotic cell lines without any toxicity and represented a valuable potential vaccine candidate and this guarantees the further evaluation towards the assessment of its immunogenicity in mice, which is currently under process.


An Unusual Cause of GI Blood Loss.
Chronic gastrointestinal bleeding is the leading cause of iron deficiency anemia in developed countries, and most occult bleeds are attributed to upper gastrointestinal tract lesions, which are broadly categorized into mass lesions, vascular, infectious, and inflammatory abnormalities. Gastric polyps account for an exceedingly small portion of these lesions but are of clinical importance because of the risk for progression to malignancy. We describe a patient found to have a gastric foveolar-type adenoma as a rare cause of iron deficiency anemia, with an incidentally found gastric neuroendocrine tumor.


metaGOflow: a workflow for the analysis of marine Genomic Observatories shotgun metagenomics data.
Genomic Observatories (GOs) are sites of long-term scientific study that undertake regular assessments of the genomic biodiversity. The European Marine Omics Biodiversity Observation Network (EMO BON) is a network of GOs that conduct regular biological community samplings to generate environmental and metagenomic data of microbial communities from designated marine stations around Europe. The development of an effective workflow is essential for the analysis of the EMO BON metagenomic data in a timely and reproducible manner. Based on the established MGnify resource, we developed metaGOflow. metaGOflow supports the fast inference of taxonomic profiles from GO-derived data based on ribosomal RNA genes and their functional annotation using the raw reads. Thanks to the Research Object Crate packaging, relevant metadata about the sample under study, and the details of the bioinformatics analysis it has been subjected to, are inherited to the data product while its modular implementation allows running the workflow partially. The analysis of 2 EMO BON samples and 1 Tara Oceans sample was performed as a use case. metaGOflow is an efficient and robust workflow that scales to the needs of projects producing big metagenomic data such as EMO BON. It highlights how containerization technologies along with modern workflow languages and metadata package approaches can support the needs of researchers when dealing with ever-increasing volumes of biological data. Despite being initially oriented to address the needs of EMO BON, metaGOflow is a flexible and easy-to-use workflow that can be broadly used for one-sample-at-a-time analysis of shotgun metagenomics data.


[Ovarian pregnancy: about 3 cases and review of the literature].
Ovarian pregnancy is a rare event among women with ectopic pregnancy in whom the ovary is the site of implantation. Its diagnosis requires a well codified approach. The peculiarities of the determining factors, of the histopathological and evolutionary features typical of ovarian pregnancies led us to focus on this form of ectopic pregnancy. We report 3 cases of ovarian pregnancy diagnosed in our Department. The three women were between 30 and 42 years, at 13 to 37 weeks of amenorrhea. All women had abdominal pain of varying intensity associated with shock. Anatomopathological examination of the right annex, normal site of implantation of ovarian pregnancies, confirmed the diagnosis. All women had juxtaposition ovarian cortical pregnancy. Ovarian pregnancy is a rare event among women with ectopic pregnancy, having specific peculiarities. Its diagnosis is difficult and is based on preoperative findings. The identification of the ovarian implantation on histopathological examination is ideal for confirming the diagnosis. Currently, it is assumed that ovarian pregnancy is the form of ectopic pregnancy which can develop to term or even result in a live birth.


TNF-alpha-induced c-Fos generation in the nucleus of the solitary tract is blocked by NBQX and MK-801.
Previous studies have shown that identified neurons of the nucleus of the solitary tract (NST) are excited by the cytokine tumor necrosis factor-alpha (TNF-alpha). Vagal afferent connections with the NST are predominantly glutaminergic. Therefore, we hypothesized that TNF-alpha effects on NST neurons may be via modulation of glutamate neurotransmission. The present study used activation of the immediate early gene product c-Fos as a marker for neuronal activation in the NST. c-Fos expression was evaluated after microinjections of TNF-alpha in the presence or absence of either the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium (NBQX) or the N-methyl-D- aspartate (NMDA) antagonist MK-801. To assess the specificity of the interaction between TNF-alpha and glutamate, c-Fos expression was also evaluated after injection of oxytocin (OT) (which has a direct excitatory effect in this area of the brain stem) in the presence and absence of NBQX or MK-801. c-Fos labeling was significantly increased in the NST after TNF-alpha exposure. Coinjection of either NBQX or MK-801 with TNF-alpha prevented significant c-Fos induction in the NST. Microinjections of OT also induced significant NST c-Fos elevation, but this expression was unaffected by coinjection of either antagonist with OT. These data lead us to conclude that TNF-alpha activation of NST neurons depends on glutamate and such an interaction is not generalized to all agonists that act on the NST.


Introduction of a new imaging guideline for suspected renal colic in the ED reduces CT urography utilisation.
Patients presenting to the ED with suspected renal colic are frequently imaged with CT urography (CTU), which rarely alters diagnosis or management. To reduce use of CTU in this population, we instigated a new imaging and management guideline in our ED. This was a quasi-experimental prospective study, whereby a new guideline was commenced at the intervention site (Monash Medical Centre) and the existing guideline continued at the control site (Dandenong Hospital). The new guideline promotes focused ultrasound for diagnosing renal colic and restricts CT to those with poor response to analgesia or 'red flags'. A consecutive series of patients with suspected renal colic were prospectively enrolled and outcomes compared between the sites. The primary outcome was CTU utilisation and secondary outcomes were radiation exposure, stone rate on CTU, admission, ED length of stay and rates of urological intervention and returns to ED at 4-week follow-up. Preintervention CTU rates were 76.7% at Monash and 72.1% at Dandenong. 324 patients were enrolled; 148 at Monash and 176 at Dandenong. Median age 47 years vs 49 years, males 76.4% vs 66.5% and medianSex, Timing, Origin, Nausea, Erythrocytes (STONE) score 10 vs 10 for Monash and Dandenong, respectively. CTU was performed in 54.1% vs 75.0% (p<0.001), median radiation exposure 2.8 vs 4.0 mSv (p<0.001) and urological intervention occurred in 16.4% vs 15.7% for Monash and Dandenong, respectively. We found that use of CTU for renal colic was significantly reduced by introduction of a guideline promoting ultrasound and encouraging selective CTU. Although intervention rates were similar between the two sites, further prospective study is needed to ensure other patient-centred outcomes do not differ.


Profession of neuropsychology in Latin America.
The purpose of this study was to analyze characteristics of individuals working in the profession of neuropsychology in Latin America in order to understand their background, professional training, current work situation, assessment and diagnostic procedures used, rehabilitation techniques employed, population targeted, teaching responsibilities, and research activities. A total of 808 professionals working in neuropsychology from 17 countries in Latin America completed an online survey between July 2013 and January 2014. The majority of participants were female and the mean age was 36.76 years (range 21-74 years). The majority of professionals working in neuropsychology in Latin America have a background in psychology, with some additional specialized training and supervised clinical practice. Over half work in private practice, universities, or private clinics and are quite satisfied with their work. Those who identify themselves as clinicians primarily work with individuals with learning problems, ADHD, mental retardation, TBI, dementia, and stroke. The majority respondents cite the top barrier in the use of neuropsychological instruments to be the lack of normative data for their countries. The top perceived barriers to the field include: lack of academic training programs, lack of clinical training opportunities, lack of willingness to collaborate between professionals, and lack of access to neuropsychological instruments. There is a need in Latin America to increase regulation, improve graduate curriculums, enhance existing clinical training, develop professional certification programs, validate existing neuropsychological tests, and create new, culturally-relevant instruments.


Land use history and population dynamics of free-standing figs in a maturing forest.
Figs (Ficus sp.) are often considered as keystone resources which strongly influence tropical forest ecosystems. We used long-term tree-census data to track the population dynamics of two abundant free-standing fig species, Ficus insipida and F. yoponensis, on Barro Colorado Island (BCI), a 15.6-km2 island in Lake Gatún, Panama. Vegetation cover on BCI consists of a mosaic of old growth (>400 years) and maturing (about 90-150 year old) secondary rainforest. Locations and conditions of fig trees have been mapped and monitored on BCI for more than 35 years (1973-2011), with a focus on the Lutz Catchment area (25 ha). The original distribution of the fig trees shortly after the construction of the Panama Canal was derived from an aerial photograph from 1927 and was compared with previous land use and forest status. The distribution of both fig species (~850 trees) is restricted to secondary forest. Of the original 119 trees observed in Lutz Catchment in 1973, >70% of F. insipida and >90% of F. yoponensis had died by 2011. Observations in other areas on BCI support the trend of declining free-standing figs. We interpret the decline of these figs on BCI as a natural process within a maturing tropical lowland forest. Senescence of the fig trees appears to have been accelerated by severe droughts such as the strong El Niño event in the year 1982/83. Because figs form such an important food resource for frugivores, this shift in resource availability is likely to have cascading effects on frugivore populations.


Feather-pecking response of laying hens to feather and cellulose-based rations fed during rearing.
Recent studies in laying hens have shown that feather peckers eat more feathers than nonpeckers. We hypothesized that food pellets containing feathers would decrease the birds' appetite for feathers and thereby also decrease feather pecking. To separate the effect of feathers from that of insoluble fiber per se, additional control groups were fed pellets containing similar amounts of cellulose. Sixty (experiment 1) and 180 (experiment 2) 1-d-old Lohmann-Selected Leghorn birds were divided into 12 groups of 5 (experiment 1) and 15 (experiment 2) birds, respectively, and kept on slatted floors. During the rearing period, 4 groups each had ad libitum access to either a commercial pelleted diet, a pelleted diet containing 5% (experiment 1) or 10% (experiment 2) of chopped feathers, respectively, or a pelleted diet containing 5% (experiment 1) or 10% (experiment 2) of cellulose, respectively. In the consecutive laying period, all groups received a commercial pelleted diet. In experiment 1, feather pecking was recorded weekly from wk 5 to wk 16. In the laying period, observations were made in wk 18, 20, 22, 23, 24, 25, 26, 27, 28, and 30. In experiment 2, feather pecking was recorded weekly from wk 5 to 11, in wk 16 to wk 18, and in wk 20 and 21. At the end of the rearing period, plumage condition per individual hen was scored. Scores from 1 (denuded) to 4 (intact) were given for each of 6 body parts. The addition of 10% of feathers to the diet reduced the number of severe feather-pecking bouts (P < 0.0129) and improved plumage condition of the back area (P < 0.001) significantly compared with control diets. The relationship between feather pecking/eating and the gastrointestinal consequences thereof, which alter feather pecking-behavior, are unclear. Understanding this relationship might be crucial for understanding the causation of feather pecking in laying hens.


Jocquestus, a new genus of trachelid sac spiders from the Afrotropical Region (Arachnida: Araneae).
The new dark sac spider genus Jocquestus gen. nov. (Araneae: Trachelidae) is proposed for two species of Afrotropical trachelid spiders, J. schenkeli (Lessert, 1923) comb. nov. (type species) from D.R. Congo, South Africa, Mozambique and Zimbabwe, and J. roeweri (Lawrence, 1938) comb. nov. from South Africa, both of which are transferred from Trachelas L. Koch, 1872. Both species are redescribed and the male of J. roeweri comb. nov. is described for the first time. Five new species are described: J. capensis sp. nov. (♂ ♀), J. harrisi sp. nov. (♀) and J. incurvus sp. nov. (♂ ♀) from South Africa, and J. griswoldi sp. nov. (♂) and J. obliquus sp. nov. (♂ ♀) from Tanzania. Present data suggests that all of the species are arboreal spiders associated with the vegetation of woody plants in savanna, forest and fynbos habitats, and are only very rarely encountered near the soil surface.


Unusually Flexible Indium(III) Metal-Organic Polyhedra Materials for Detecting Trace Amounts of Water in Organic Solvents and High Proton Conductivity.
Humidity-induced single-crystal transformation was observed in the indium metal-organic polyhedra [In2(TCPB)2]·2H2O (In1), where H3TCPB is 1,3,5-tri(4-carboxyphenoxy)benzene. When the humidity is above 58% relative humidity (RH) at room temperature, the neutral compound In1 could be successfully converted into the positively charged compound In1-H along with the color change from yellow to deep red, which also undergoes a reversible transformation into In1 driven by thermal dehydration. Notably, the color of In1 takes only 5 min to change under 58% RH at room temperature, which is much quicker than common desiccant bluestone. As the water content is increased from 0.0% to 0.2% in acetonitrile solvent, compound In1 exhibits rapid detection of trace amounts of water through turn-off luminescence sensing mechanism with a low detection limit of 2.95 × 10-4%. Because of the formation of extensive hydrogen-bonding network between the metal-organic polyhedra (MOPs) and surrounding guest OH- ions, compound In1-H, along with isostructural Ga1-H, displays excellent proton conductivity up to 2.84 × 10-4 and 2.26 × 10-4 S cm-1 at 298 K and 98% RH, respectively. Furthermore, the activation energies are found to be 0.28 eV for In1-H and 0.34 eV for Ga1-H. This method of incorporation of OH- ions to obtain high proton conductivity MOPs with low activation energy demonstrates the advantage of OH- ion conduction in the solid-state materials.


[Hemangioperocytoma in the infant. A histogenetic study].
Two children with hemangiopericytomas are reported-one with a congenital tumor, the second hemangiopericytoma was noticed during the first trimenon. Histologically there was no obvious difference to the hemangiopericytomas in adults. Tumor immaturity should not be seen as a nondifferentiation but as an embryonal immaturity. In analogy to other reticulo-histiocytic proliferations, reticular fibers, shown by silver impregnation, can be demonstrated in both cases. The silver stain should not be over-rated in its diagnostic and prognostic significance.


Characterization of neuromedin U effects in canine smooth muscle.
Two endogenous receptors for the potent smooth muscle-stimulating peptide neuromedin U (NmU) have recently been identified and cloned. Pharmacological, binding, and expression studies were conducted in an attempt to determine the receptor(s) involved in the smooth muscle-stimulating effects of NmU. The NmU peptides caused a concentration-dependent contraction of canine isolated urinary bladder. NmU did not have this same effect in the urinary bladder from rat, guinea pig, rabbit, mouse, or ferret. Although NmU had no effect on canine uterus it did cause contraction of canine stomach, ileum, and colon. As well as causing contraction of canine bladder in vitro, NmU administered systemically resulted in a significant increase in urinary bladder pressure in vivo. High-affinity binding sites for NmU were identified in canine bladder. The four NmU peptides porcine NmU-8, rat NmU-23, human NmU-25, and porcine NmU-25 displaced (125)I-NmU-25 binding with similar K(i) values (0.08-0.24 nM). A different binding profile was revealed in human embryonic kidney-293 cells transiently expressed with the canine NmU-2 receptor where porcine NmU-8 (K(i) = 147.06 nM) was much less potent than the other NmU peptides. Using TaqMan, expression of NmU-1 was detected in human urinary bladder, small intestine, colon, and uterus. Expression of NmU-2 was much lower or absent in these human tissues and undetectable in canine bladder and stomach. The results of this study reveal significant species differences in the activity of NmU. The contractile activity in human and canine smooth muscle seems to be mediated by the recently cloned NmU-1 receptor.


Bright fluorescent silica-nanoparticle probes for high-resolution STED and confocal microscopy.
In recent years, fluorescent nanomaterials have gained high relevance in biological applications as probes for various fluorescence-based spectroscopy and imaging techniques. Among these materials, dye-doped silica nanoparticles have demonstrated a high potential to overcome the limitations presented by conventional organic dyes such as high photobleaching, low stability and limited fluorescence intensity. In the present work we describe an effective approach for the preparation of fluorescent silica nanoparticles in the size range between 15 and 80 nm based on L-arginine-controlled hydrolysis of tetraethoxysilane in a biphasic cyclohexane-water system. Commercially available far-red fluorescent dyes (Atto647N, Abberior STAR 635, Dy-647, Dy-648 and Dy-649) were embedded covalently into the particle matrix, which was achieved by aminosilane coupling. The physical particle attributes (particle size, dispersion, degree of agglomeration and stability) and the fluorescence properties of the obtained particles were compared to particles from commonly known synthesis methods. As a result, the spectroscopic characteristics of the presented monodisperse dye-doped silica nanoparticles were similar to those of the free uncoupled dyes, but indicate a much higher photostability and brightness. As revealed by dynamic light scattering and ζ-potential measurements, all particle suspensions were stable in water and cell culture medium. In addition, uptake studies on A549 cells were performed, using confocal and stimulated emission depletion (STED) microscopy. Our approach allows for a step-by-step formation of dye-doped silica nanoparticles in the form of dye-incorporated spheres, which can be used as versatile fluorescent probes in confocal and STED imaging.


Serum copper and zinc in rheumatoid arthritis and osteoarthritis.
Serum copper, zinc and caeruloplasmin levels were measured in 49 patients with active rheumatoid arthritis, in 33 patients with osteoarthritis and a group of blood donor controls. Serum copper and caeruloplasmin levels in the osteoarthritic patients were significantly higher and serum zinc levels significantly lower than in the blood donor controls. Although these differences could not be accounted for on the basis of age or drug administration neither did they correlate with a radiological grading of disease severity. Copper and caeruloplasmin levels were raised in the rheumatoid group as compared to both osteoarthritic and control groups. These were strong correlations between serum copper, caeruloplasmin, ESR and alpha 1 globulin levels in the rheumatoid patients. Although caeruloplasmin-bound copper accounted for most of the elevation in serum copper levels in the rheumatoid group, the calculated non-caeruloplasmin bound copper level was also elevated in rheumatoid, as compared to osteoarthritic patients. Serum zinc levels in the rheumatoid group were lower than in the control group but not significantly different to those in the osteoarthritic group.


Low heritability and high phenotypic plasticity of salivary cortisol in response to environmental heterogeneity in a wild pinniped.
Individuals are unique in how they interact with and respond to their environment. Correspondingly, unpredictable challenges or environmental stressors often produce an individualized response of the hypothalamic-pituitary-adrenal (HPA) axis and its downstream effector cortisol. We used a fully crossed, repeated measures design to investigate the factors shaping individual variation in baseline cortisol in Antarctic fur seal pups and their mothers. Saliva samples were collected from focal individuals at two breeding colonies, one with low and the other with high density, during two consecutive years of contrasting food availability. Mothers and pups were sampled concurrently at birth and shortly before weaning, while pups were additionally sampled every 20 days. We found that heritability was low for baseline cortisol, while within-individual repeatability and among-individual variability were high. A substantial proportion of the variation in baseline cortisol could be explained in pups and mothers by a combination of intrinsic and extrinsic factors including sex, weight, day, season, and colony of birth. Our findings provide detailed insights into the individualization of endocrine phenotypes and their genetic and environmental drivers in a wild pinniped. Furthermore, the strong associations between cortisol and life history traits that we report in fur seals could have important implications for understanding the population dynamics of species impacted by environmental change.


C.A.U.S.E.: Cardiac arrest ultra-sound exam--a better approach to managing patients in primary non-arrhythmogenic cardiac arrest.
Cardiac arrest is a condition frequently encountered by physicians in the hospital setting including the Emergency Department, Intensive Care Unit and medical/surgical wards. This paper reviews the current literature involving the use of ultrasound in resuscitation and proposes an algorithmic approach for the use of ultrasound during cardiac arrest. At present there is the need for a means of differentiating between various causes of cardiac arrest, which are not a direct result of a primary ventricular arrhythmia. Identifying the cause of pulseless electrical activity or asystole is important as the underlying cause is what guides management in such cases. This approach, incorporating ultrasound to manage cardiac arrest aids in the diagnosis of the most common and easily reversible causes of cardiac arrest not caused by primary ventricular arrhythmia, namely; severe hypovolemia, tension pneumothorax, cardiac tamponade, and massive pulmonary embolus. These four conditions are addressed in this paper using four accepted emergency ultrasound applications to be performed during resuscitation of a cardiac arrest patient with the aim of determining the underlying cause of a cardiac arrest. Identifying the underlying cause of cardiac arrest represents the one of the greatest challenges of managing patients with asystole or PEA and accurate determination has the potential to improve management by guiding therapeutic decisions. We include several clinical images demonstrating examples of cardiac tamponade, massive pulmonary embolus, and severe hypovolemia secondary to abdominal aortic aneurysm. In conclusion, this protocol has the potential to reduce the time required to determine the etiology of a cardiac arrest and thus decrease the time between arrest and appropriate therapy.


[Inter-observer agreement on histological diagnosis of colorectal polyps: the APACC study].
Adenomas are considered as precursors of colorectal adenocarcinomas. After polypectomy, surveillance depends on the histological analysis of the excised polyps. The aim of the study was to evaluate the reproducibility of the histological diagnosis performed by pathologists from participating centers in the APACC study. Their interpretations were compared to those of the study's consensual diagnosis performed by two reference pathologists. The agreement proportion and the concordance coefficient (kappa) were estimated for 326 polyps obtained from the first 148 patients included. A concordant diagnosis for the adenomatous nature was shown for 246 of the 255 adenomas (96%). The diagnosis of both the histological type and the degree of dysplasia was concordant for only 92 of the 255 adenomas (36%). Kappa values were 0.67 for the adenomatous nature, 0.46 for the histological types, and 0.26 for the degree of dysplasia. A high degree of agreement was obtained for the diagnosis of the adenomatous nature. By contrast, high variations were observed for the interpretations of the histological type and the degree of dysplasia.


Magnetic properties of isostructural BaCoP2O7, BaNiP2O7, and BaCuP2O7 studied with dc and ac magnetization and specific heat.
Magnetic properties of three isostructural compounds BaMP2O7 (M = Co, Ni, and Cu) were investigated by dc and ac magnetization and specific heat measurements. BaCuP2O7 was shown to be an excellent quasi-one-dimensional linear-chain Heisenberg antiferromagnet with an exchange constant (J/kB) of 103.8 K (Hamiltonian H = J Sigma SiS(i+1)) and a temperature for the long-range magnetic order (TN) of 0.81 K giving the ratio kBTN/J = 0.78%. BaCoP2O7 and BaNiP2O7 exhibited long-range antiferromagnetic order at TN = 10.4 and 10.1 K, respectively. BaCoP2O7 and BaNiP2O7 showed a large contribution of the short-range correlation above TN. BaNiP2O7 remained in the antiferromagnetic state up to 90 kOe at 2 K, whereas BaCoP2O7 demonstrated two metamagnetic phase transitions at about 52 and 71 kOe at 2 K if the magnetic field was parallel to the easy direction. BaMP2O7 melted incongruently at 1323 K (M = Co), 1344 K (M = Ni), and 1338 K (M = Cu).


A newly identified deletion of 970 bp at the alpha-globin locus that removes the promoter region of the alpha1 gene.
The most common causes of alpha-thalassemia (thal) are deletions that remove a part, or one or both of the functional alpha-globin genes. These deletions cause diminished expression of the alpha-globin protein, which may result in relatively low hemoglobin (Hb) and/or mean corpuscular volume (MCV) values. We here report the identification of a 970 bp deletion in the alpha1-globin gene that encompasses the entire promoter region of the alpha1-globin gene and 26 bp encoding the 5' end of the mRNA. Thus, the affected alpha1-globin gene is prone to be nonfunctional. We therefore nominated the newly identified deletion allele alpha-alphaDelta970. The MCV values of four related carriers of the alpha-alphaDelta970 allele were slightly lowered, consistent with the presence of three functional alpha-globin genes.


Surgical interventions for chronic pelvic pain.
The objective of this study is to review an evidence-based approach to surgical treatment of key chronic pelvic pain (CPP) contributors emphasizing the importance of preoperative evaluation and counseling. CPP is a poorly understood but highly prevalent condition and there are limited, well constructed studies to guide effective, durable treatment. CPP arises from factors originating in multiple organ systems, including reproductive, urologic, gastrointestinal, and myofascial, all informing the central nervous system. For those with severe disabling conditions, who have a suboptimal response to medical management, surgical interventions can be offered for diagnostic evaluation and/or treatment. Leiomyoma, adenomyosis, adnexal disorder, pelvic adhesions, and pelvic varicosities are common considerations in the differential diagnosis of CPP amenable to surgical approach. Surgical treatments of CPP range from conservative/fertility-sparing approaches to extirpative therapy. Consistently, successful outcomes often are predicated on correctly identifying the abnormal peripheral pain process (which often is only part of the complete picture for these patients). Further research is needed to better guide clinicians as to when to choose surgical therapy vs. targeting secondary contributors to pelvic pain.


Maturation of baseline breathing and of hypercapnic and hypoxic ventilatory responses in newborn mice.
Breathing during the first postnatal hours has not been examined in mice, the preferred mammalian species for genetic studies. We used whole body plethysmography to measure ventilation (VE), breath duration (T(TOT)), and tidal volume (VT) in mice delivered vaginally (VD) or by cesarean section (CS). In experiment 1, 101 VD and 100 CS pups aged 1, 6, 12, 24, or 48 h were exposed to 8% CO2 or 10% O2 for 90 s. In experiment 2, 31 VD pups aged 1, 12, or 24 h were exposed to 10% O2 for 5 min. Baseline breathing maturation was delayed in CS pups, but VE responses to hypercapnia and hypoxia were not significantly different between VD and CS pups [at postnatal age of 1 h (H1): 48 +/- 44 and 18 +/- 32%, respectively, in VD and CS pups combined]. The VE increase induced by hypoxia was greater at H12 (46 +/- 27%) because of T(TOT) response maturation. At all ages, hypoxic decline was ascribable mainly to a VT decrease, and posthypoxic decline was ascribable to a T(TOT) increase with apneas, suggesting different underlying neuronal mechanisms.


[Review of the development of pharmacy and apothecaries in Bosnia and Herzegovina and in the area of Sarajevo].
The development of pharmacy and dispensaries in Bosnia and Herzegovina started very early and it could be divided into several periods from which we select the period of Turkish and Austro-Hungarian rules as they had organized activities. In remote times, beginnings of treatment of diseases belong to herbalists who in our parts even then were a significant guild. That guild saw an intensive development in the times of Turkish rule. In Sarajevo, the sale of medicines in shops was established as early as that period. They resembled today's drugstores and had supervision of the condition and use of medicines which was done strictly. The Austro-Hungarian period in Bosnia and Herzegovina meant a great change in the development of pharmacy and health care generally and since then pharmacy and dispensaries in Bosnia and Herzegovina have been organized according to European standards, while the care of making dispensing and trading in medicines was taken over by trained pharmacists.


Quadruple therapy for asymptomatic COVID-19 infection patients.
The novel coronavirus (COVID-19) is currently in epidemic stage. After large-scale interpersonal infection, asymptomatic patients appear. Whether asymptomatic patients are contagious or not and whether they need medication are the arguments among clinical experts. This paper reports a special asymptomatic couple with COVID-19, of which the male patient is an intercity bus driver but has not induced confirmed infection of his 188 passengers. The patients were treated with four combinations of lopinavir/ritonavir tablets, arbidol tablets, Lianhuaqingwen granules, and recombinant human interferon-α2b (IFN-α2b) injection via aerosol. Their clinical characteristics and medication were summarized and analyzed. The two asymptomatic patients far away from Wuhan did not seem to be highly contagious. They improved obviously, after treatment with the quadruple therapy, but the effective drug is still unknown. It should be noted that lopinavir/ritonavir tablets have many drug interactions and are the most likely drugs to cause hyperlipidemia and hyperglycemia in these two patients. IFN-α2b is more effective in the early stage of virus infection. Arbidol instruction dose may not be sufficient to inhibit the novel coronavirus in vivo. The evidence-based medicine of Lianhuaqingwen granules for treating various viral infections is just based on Chinese patients.