Coordinated planning for science in communist europe.
The Council is not engaged in the supranational formulation of policy and planning on scientific research and technology, but has made considerable progress in coordinating research policies and plans on a limited number of scientific and technical problems of priority interest and of common concern to all members. The establishment of national science-planning institutions in CEMA countries and the adoption of a uniform approach to the formulation of national science policies and plans must be considered basic procedures for achieving international coordination of their efforts. The creation of organizational units within CEMA to deal specifically with the coordination of science policies and plans represents a strengthening of the institutional framework that is necessary for coordination of an internationally cooperative effort in research and technology. Moreover, CEMA's 1-year plan for science and technology has probably been of considerable value as a pilot project for the formulation of the research plan for 1966-70. The delineation of a limited number of important scientific and technical problems of common interest to the members, and the allocation of research projects to a country having the highest capability to conduct them, hold considerable promise for financial savings and for improved utilization of the limited scientific manpower and research facilities of the CEMA countries. While all these measures are significant in CEMA's attempt to improve coordination of science policy and planning, only time will enable true assessment of their effectiveness. The Council's scheme for the specialization of labor in research and technology has met and will undoubtedly continue to meet, considerable opposition by various segments of the scientific communities because of deep-rooted and long-standing national prejudices, and reluctance of vested interests to give up research activities in which they are interested and to which their professional futures are tied. Moreover, opposition to CEMA-sponsored programs for specialization in research will continue to stem from the desire of some member countries further to reduce Russian influence in their domestic affairs. While recognizing the financial savings that can accrue to them from division of labor in research within CEMA, the smaller countries cannot be unaware that there is probably a limit to which the Soviet Union, with its vast scientific and technological base, is willing to participate in the division of-labor scheme. As a world power, the Soviet Union can hardly become dependent upon other members of CEMA in any field. Nevertheless, by promoting the coordination of research plans and a division of labor among CEMA members, the Soviet Union stands to gain by having its scientific-research effort augmented in several fields by the efforts of other members.


Associations between clinical diagnostic criteria and pretreatment patient-reported outcomes measures in a prospective observational cohort of patients with neurogenic thoracic outlet syndrome.
Neurogenic thoracic outlet syndrome (NTOS) is caused by dynamic compression of the brachial plexus at the level of the supraclavicular scalene triangle or the subcoracoid (pectoralis minor) space, or both. The purpose of this study was to characterize relationships between 14 clinical diagnostic criteria (CDC) and seven pretreatment patient-reported outcomes measures (PROMs) in a prospective cohort of patients with NTOS. There were 183 new patient referrals between July 1 and December 31, 2015, with 150 (82%) meeting an established set of predefined CDC for NTOS. PROMs were evaluated across five domains: pain severity, functional disability, depression, quality of life, and pain catastrophizing. Linear regression and Pearson correlation statistics were used to analyze associations between CDC and PROMs. Mean ± standard error patient age was 37.1 ± 1.1 years (range, 12-66 years), and 107 (71%) were women. Five (3%) had a cervical rib, and 15 (10%) had recurrent NTOS. The most frequently positive CDC were neck or upper extremity pain (99%), upper extremity or hand paresthesia (94%), symptom exacerbation by arm elevation (97%), localized supraclavicular or subcoracoid tenderness to palpation (96%), and a positive 3-minute elevated arm stress test (94%; mean duration, 102.0 ± 5.1 seconds). The number of positive CDC (mean, 9.6 ± 0.1) correlated with the degree of tenderness to palpation and the duration of elevated arm stress test, as well as with PROMs for pain severity, functional disability, depression, physical quality of life, and pain catastrophizing (all P < .0001). PROMs across multiple domains were also strongly correlated with each other. Patients with clinically significant pain catastrophizing exhibited a greater level of functional disability than noncatastrophizing patients (P < .0001). This study illustrates the relative strengths of 14 CDC and seven PROMs to evaluate patients with NTOS, helping validate the selected CDC and highlighting the potential role of pain catastrophizing in functional disability. This cohort will provide valuable information on the utility of different CDC and PROMs to predict treatment outcomes.


Reconstruction of dynamic contrast enhanced magnetic resonance imaging of the breast with temporal constraints.
A number of methods using temporal and spatial constraints have been proposed for reconstruction of undersampled dynamic magnetic resonance imaging (MRI) data. The complex data can be constrained or regularized in a number of different ways, for example, the time derivative of the magnitude and phase image voxels can be constrained separately or jointly. Intuitively, the performance of different regularizations will depend on both the data and the chosen temporal constraints. Here, a complex temporal total variation (TV) constraint was compared to the use of separate real and imaginary constraints, and to a magnitude constraint alone. Projection onto Convex Sets (POCS) with a gradient descent method was used to implement the diverse temporal constraints in reconstructions of DCE MRI data. For breast DCE data, serial POCS with separate real and imaginary TV constraints was found to give relatively poor results while serial/parallel POCS with a complex temporal TV constraint and serial POCS with a magnitude-only temporal TV constraint performed well with an acceleration factor as large as R=6. In the tumor area, the best method was found to be parallel POCS with complex temporal TV constraint. This method resulted in estimates for the pharmacokinetic parameters that were linearly correlated to those estimated from the fully-sampled data, with K(trans,R=6)=0.97 K(trans,R=1)+0.00 with correlation coefficient r=0.98, k(ep,R=6)=0.95 k(ep,R=1)+0.00 (r=0.85). These results suggest that it is possible to acquire highly undersampled breast DCE-MRI data with improved spatial and/or temporal resolution with minimal loss of image quality.


The role of AGEs in cardiovascular disease.
Advanced glycation end-products (AGEs) are generated in the diabetic milieu, as a result of chronic hyperglycemia and enhanced oxidative stress. These AGEs, via direct and receptor dependent pathways promote the development and progression of cardiovascular disease. AGEs accumulate at many sites of the body including the heart and large blood vessels in diabetes. These modified proteins interact with receptors such as RAGE to induce oxidative stress, increase inflammation by promoting NFkappaB activation and enhance extracellular matrix accumulation. These biological effects translate to accelerated plaque formation in diabetes as well as increased cardiac fibrosis with consequent effects on cardiac function. Strategies to reduce the ligation of AGEs to their receptors such as agents which reduce AGE accumulation, soluble RAGE which acts as a competitive antagonist to the binding of AGEs to RAGE and genetic deletions of RAGE appear to attenuate diabetes associated atherosclerosis. Benefits on cardiac dysfunction with these inhibitors of the AGE/RAGE axis are not as well characterised. In conclusion, therapeutic strategies targeting AGEs appear to have significant clinical potential, often in combination with currently used agents such as inhibitors of the renin-angiotensin system, to reduce the major burden of diabetes, its associated cardiovascular complications.


The impact of new immigrants from the former Soviet Union on the severity of coronary angiographic findings in a public hospital in Israel.
The arrival of 610,000 new immigrants to Israel from the former Soviet republics accounted for 58% of the population growth in the early 1990's. To compare the coronary angiographic findings and risk factors between the new immigrants and local Jewish and Arab patients in this era of cost containment. A total of 550 consecutive patients--314 Jews, 95 new immigrants and 141 Arabs--were catheterized and analyzed during a 5 month period in 1995. Of this group 403 were males (73%). The mean age was 63.6 +/- 10.2 years among new immigrants, 62.4 +/- 9.4 among Jews, and 55.1 +/- 10.9 among Arabs (P < 0.05). Immigrants, including those under age 60, had the highest prevalence of multivessel disease (88.7%). Arabs had a high prevalence of single vessel disease (34.6%) and a low prevalence of multivessel (65.4%) and left main coronary disease (5.6%). Age, gender, risk factors and ethnic origin in descending order were determinants of the extent of coronary angiographic disease as revealed by multiple regression analysis. New immigrants had the most extensive angiographic coronary involvement, while Arab patients were younger and had less severe coronary artery disease. More intensive risk factor modification may have a major impact on disease progression particularly in the new immigrant subgroup.


ZFC3H1, a zinc finger protein, modulates IL-8 transcription by binding with celastramycin A, a potential immune suppressor.
Celastramycin A, a small molecule that inhibits the production of antibacterial peptides in an ex vivo culture system of Drosophila, suppresses the TNFα-mediated induction of IL-8 in mammalian cells. To understand its molecular mechanism, we examined Celastramycin A binding proteins and investigated their biological functions. Our screening and subsequent pull-down assay revealed ZFC3H1 (also known as CCDC131 or CSRC2), an uncharacterized zinc finger protein, as a Celastramycin A binding protein. The knockdown of ZFC3H1 reduced IL-8 expression levels in the TNFα-stimulated lung carcinoma cell line, LU99, and UV-irradiated HeLa cells. Based on reporter assay results, we concluded that ZFC3H1 participates in the transcriptional activation of IL-8. The findings of our UV-irradiation experiments implied that ZFC3H1 may indirectly interact with ERCC1 in an activated DNA repair complex. Thus, we designated ZFC3H1 as a mammalian target of Celastramycin A (mTOC).


Weissella confusa (basonym: Lactobacillus confusus) bacteremia: a case report.
Infection with Lactobacillus is rare, and only a handful of species have been identified as being clinically significant: Lactobacillus casei, Lactobacillus rhamnosus, and Lactobacillus leichmannii. The literature contains one case report of bacteremia caused by Weissella confusa (basonym: Lactobacillus confusus), but the clinical significance of the infection was unclear. We describe a case of W. confusa bacteremia in a 46-year-old man with a history of abdominal aortic dissection and repair. This procedure was complicated by gut ischemia, which necessitated massive small bowel resection. He subsequently developed short-bowel syndrome, which required him to have total parenteral nutrition. He later developed an Enterococcus faecalis aortic valve endocarditis that required a coronary artery bypass graft and aortic root replacement with homograft and 6 weeks of intravenous ampicillin and gentamicin. Three months prior to his most recent admission, he was diagnosed with Klebsiella pneumoniae bacteremia and candidemia. At the present admission, he had fever (T(max), 39.5 degrees C) and chills of 2 days' duration and was admitted to the intensive care unit because of hemodynamic instability. Blood cultures grew K. pneumoniae and W. confusa in four of four blood culture bottles (both aerobe and anaerobe bottles). Imaging studies failed to find any foci of infection. A transesophageal echocardiogram revealed no vegetations. A culture of the patient's Hickman catheter tip was negative. The patient was treated with piperacillin-tazobactam and gentamicin. His condition improved, and he was discharged home, where he completed 4 weeks of piperacillin-tazobactam therapy. Lactobacillemia seldom results in mortality; however, it may be a marker of a serious underlying disease. It is usually seen in patients who have a complex medical history or in patients who receive multiple antibiotics. Lactobacillus spp. are generally associated with polymicrobial infections, and when isolated from the blood, they need to be considered possible pathogens. The presence of a vancomycin-resistant, gram-positive coccobacilli on a blood culture should alert clinicians to the possibility of bacteremia caused by W. confusa or other small gram-positive rods.


Detection of measles virus-specific interferon-gamma-secreting T-cells by ELISPOT.
The enzyme-linked immunospot (ELISPOT) assay is a highly sensitive tool used to measure the frequency of antigen-specific T-cells in vitro. Among its many applications, this assay is useful for the characterization of cellular immune responses after immunization against measles and other viral pathogens. A description of the measles virus-specific interferon (IFN)-gamma ELISPOT assay optimized in our laboratory is described in detail in this chapter. Procedures for the preparation of measles virus, infection of peripheral blood mononuclear cells with measles virus, and the IFN-gamma ELISPOT assay are also outlined. These methods can also be broadly adapted to measure activated T-cells to other viral pathogens and/or pathogen-derived peptides. Therefore, the ELISPOT assay can be used for the design, development, and evaluation of new vaccines.


Bortezomib sensitizes human osteosarcoma cells to adriamycin-induced apoptosis through ROS-dependent activation of p-eIF2α/ATF4/CHOP axis.
Osteosarcoma is the most common bone cancer, and chemotherapy is currently indispensable for its treatment. Adriamycin has been claimed to be the most effective agent for osteosarcoma, however, the outcome of adriamycin chemotherapy remains unsatisfactory. Here, we reported a potent combination therapy that bortezomib, a proteasome inhibitor, enhances adriamycin-induced apoptosis to eliminate osteosarcoma cells and we revealed that the activation of p-eIF2α/ATF4/CHOP axis is the underlying associated mechanisms. First, we observed that bortezomib enhances adriamycin-mediated inhibition of cell proliferation and enhances the apoptosis in osteosarcoma cell lines. Moreover, this drug combination produced more potent tumor-growth inhibitory effects in human osteosarcoma cell line KHOS/NP xenografts. Our study showed that reactive oxygen species (ROS) plays an important role in apoptosis induced by adriamycin plus bortezomib, whereas ROS scavenger NAC could almost completely block the apoptosis induced by the combination treatment. Meanwhile, p-eIF2α is remarkably elevated in the combination group. As a result, ATF4 exhibits strong activation which consequently induces the activation of CHOP and leads to the cell death. Finally, 13 primary osteosarcoma cells demonstrated potent response to the combination treatment. In a human osteosarcoma patient-derived xenograft (PDX) model, our finding suggests that when combined with bortezomib, a relatively low dose of adriamycin produced more potent tumor-growth inhibitory effects without increased toxicity. Thus, our findings not only provide a promising combination strategy to overcome osteosarcoma but also shed new light on the strategy of combining increased ROS and inhibited proteasome to open up new opportunities for the clinical development of chemotherapy regimens.


[Irbesartan in clinical practice].
Irbesartan is a noncompetitive angiotensin II receptor type 1 antagonist which has been successfully used for more than 10 years for the treatment of hypertensive disease. In a dose of 150-300 mg/day irbesartan produces long term effect for 24 hours. Its antihypertensive efficacy is augmented by concomitant administration of hydrochlorothiazide. Irbesartan reduces left ventricular hypertrophy and increases probability of maintenance of sinus rhythm after cardioversion of atrial fibrillation. Renoprotective effects of irbesartan has been demonstrated both at early and late stages of kidney involvement in patients with type 2 diabetes. Therapeutic efficacy and safety of irbesartan ensure high level of patients compliance. Irbesartan as monotherapy or as combination with hydrochlorothiazide demonstrate contemporary therapeutic approach to arterial hypertension as well as to diabetic nephropathy both at its early and late stages.


Assessing the impact of widespread respirator use in curtailing COVID-19 transmission in the USA.
Dynamic models are used to assess the impact of three types of face masks (cloth masks, surgical/procedure masks and respirators) in controlling the COVID-19 pandemic in the USA. We showed that the pandemic would have failed to establish in the USA if a nationwide mask mandate, based on using respirators with moderately high compliance, had been implemented during the first two months of the pandemic. The other mask types would fail to prevent the pandemic from becoming established. When mask usage compliance is low to moderate, respirators are far more effective in reducing disease burden. Using data from the third wave, we showed that the epidemic could be eliminated in the USA if at least 40% of the population consistently wore respirators in public. Surgical masks can also lead to elimination, but requires compliance of at least 55%. Daily COVID-19 mortality could be eliminated in the USA by June or July 2021 if 95% of the population opted for either respirators or surgical masks from the beginning of the third wave. We showed that the prospect of effective control or elimination of the pandemic using mask-based strategy is greatly enhanced if combined with other non-pharmaceutical interventions (NPIs) that significantly reduce the baseline community transmission. By slightly modifying the model to include the effect of a vaccine against COVID-19 and waning vaccine-derived and natural immunity, this study shows that the waning of such immunity could trigger multiple new waves of the pandemic in the USA. The number, severity and duration of the projected waves depend on the quality of mask type used and the level of increase in the baseline levels of other NPIs used in the community during the onset of the third wave of the pandemic in the USA. Specifically, no severe fourth or subsequent wave of the pandemic will be recorded in the USA if surgical masks or respirators are used, particularly if the mask use strategy is combined with an increase in the baseline levels of other NPIs. This study further emphasizes the role of human behaviour towards masking on COVID-19 burden, and highlights the urgent need to maintain a healthy stockpile of highly effective respiratory protection, particularly respirators, to be made available to the general public in times of future outbreaks or pandemics of respiratory diseases that inflict severe public health and socio-economic burden on the population.


Complex regional pain syndrome I (CRPS I): prospective study and laboratory evaluation.
To relate clinical features to autonomic laboratory indices used in the diagnosis of Complex Regional Pain Syndrome type I (CRPS I) (reflex sympathetic dystrophy) to generate improved diagnostic criteria. CRPS I is a chronic pain syndrome, characterized by diffuse limb pain with allodynia and prominent vasomotor and sudomotor dysfunction. We conducted a prospective study on 102 patients referred for possible CRPS I. These patients completed a structured questionnaire and underwent neurologic examination, with special attention to the evaluation of clinical features of vasomotor, sudomotor, motor, and sensory, including pain, dysfunction. All patients were tested using a standard autonomic protocol that compared side-to-side skin temperature, resting sweat output, and quantitative sudomotor axon reflex test (QSART) measurements. Composite autonomic clinical (CRPS-Sx) and laboratory (CRPS-LAB) scores were defined. The clinical (subjective and objective) and the laboratory data were analyzed using Pearson's correlation analysis and Bonferroni's probability value to assess concordance and their value in correctly diagnosing CRPS I. All cases occurred after limb injury. One-third of cases did not fulfill our criteria of CRPS I. Highly significant correlations (p<.001) were found among certain clusters of symptoms and signs that shared unifying pathophysiologies. CRPS-Sx correlated with CRPS-LAB (p = .035). The indices that correlated most reliably with clinical data and with each other were RSO, QSART, and skin temperature reductions. Clinical and autonomic laboratory probability scores correlate in an internally consistent manner. Both CRPS-Sx and CRPS-LAB are sensitive and reliable tools to formulate a correct diagnosis of CRPS I and can be combined to provide an improved set of diagnostic criteria for CRPS I.


Resource-rational Models of Human Goal Pursuit.
Goal-directed behavior is a deeply important part of human psychology. People constantly set goals for themselves and pursue them in many domains of life. In this paper, we develop computational models that characterize how humans pursue goals in a complex dynamic environment and test how well they describe human behavior in an experiment. Our models are motivated by the principle of resource rationality and draw upon psychological insights about people's limited attention and planning capacities. We find that human goal pursuit is qualitatively different and substantially less efficient than optimal goal pursuit in our simulated environment. Models of goal pursuit based on the principle of resource rationality capture human behavior better than both a model of optimal goal pursuit and heuristics that are not resource-rational. We conclude that the way humans pursue goals is shaped by the need to achieve goals effectively as well as cognitive costs and constraints on planning and attention. Our findings are an important step toward understanding humans' goal pursuit as cognitive limitations play a crucial role in shaping people's goal-directed behavior.


Predicting Sepsis Mortality in a Population-Based National Database: Machine Learning Approach.
Although machine learning (ML) algorithms have been applied to point-of-care sepsis prognostication, ML has not been used to predict sepsis mortality in an administrative database. Therefore, we examined the performance of common ML algorithms in predicting sepsis mortality in adult patients with sepsis and compared it with that of the conventional context knowledge-based logistic regression approach. The aim of this study is to examine the performance of common ML algorithms in predicting sepsis mortality in adult patients with sepsis and compare it with that of the conventional context knowledge-based logistic regression approach. We examined inpatient admissions for sepsis in the US National Inpatient Sample using hospitalizations in 2010-2013 as the training data set. We developed four ML models to predict in-hospital mortality: logistic regression with least absolute shrinkage and selection operator regularization, random forest, gradient-boosted decision tree, and deep neural network. To estimate their performance, we compared our models with the Super Learner model. Using hospitalizations in 2014 as the testing data set, we examined the models' area under the receiver operating characteristic curve (AUC), confusion matrix results, and net reclassification improvement. Hospitalizations of 923,759 adults were included in the analysis. Compared with the reference logistic regression (AUC: 0.786, 95% CI 0.783-0.788), all ML models showed superior discriminative ability (P<.001), including logistic regression with least absolute shrinkage and selection operator regularization (AUC: 0.878, 95% CI 0.876-0.879), random forest (AUC: 0.878, 95% CI 0.877-0.880), xgboost (AUC: 0.888, 95% CI 0.886-0.889), and neural network (AUC: 0.893, 95% CI 0.891-0.895). All 4 ML models showed higher sensitivity, specificity, positive predictive value, and negative predictive value compared with the reference logistic regression model (P<.001). We obtained similar results from the Super Learner model (AUC: 0.883, 95% CI 0.881-0.885). ML approaches can improve sensitivity, specificity, positive predictive value, negative predictive value, discrimination, and calibration in predicting in-hospital mortality in patients hospitalized with sepsis in the United States. These models need further validation and could be applied to develop more accurate models to compare risk-standardized mortality rates across hospitals and geographic regions, paving the way for research and policy initiatives studying disparities in sepsis care.


[Possible means for increasing exotoxin synthesis by a Bacillus thuringiensis culture--the producer of bitoxibacillin].
Various procedures were studied for obtaining Bacillus thuringiensis strains of serotype I which synthesized exotoxins. Mutant clones with elevated exotoxin synthesis could be selected by treating the cells with N-methyl-N-nitro-N-nitrosoguanidine. The frequency of (+) variant selection was from 17 to 12 X 10(-2). The clones of S and R types differed in the insecticide activity of the exotoxin. Its yield could be increased by optimizing the composition of growth media. The strain specificity of B. thuringiensis producing the exotoxin was assayed in terms of carbon and nitrogen requirements.


Peripheral Ulcerative Keratitis Associated With Lichen Planus.
The aim of this study was to report a case of peripheral ulcerative keratitis (PUK) associated with lichen planus. A 42-year-old woman with histological confirmation of lichen planus from an oral buccal mucosa biopsy presented with bilateral peripheral stromal thinning and an epithelial defect, in keeping with PUK. All screening for known causes of PUK were negative, and lichen planus was presumed as the etiological factor. Oral prednisolone 1 mg/kg was initiated, alongside topical steroids and topical ciclosporin. The PUK resolved after 3 months, and a slow-tapering regimen of oral prednisolone was needed to prevent a relapse of ocular surface inflammation. Topical steroids were also tapered and discontinued after 5 months, and the ocular surface remained stable with topical ciclosporin with no relapse after 1 year. Ocular manifestations of lichen planus are rare and mostly involve the conjunctiva; however, PUK might also develop, presumably due to its similar mechanisms with other T-cell autoimmune diseases. Systemic immunosuppression is required initially but further control of the ocular surface can be achieved successfully with topical ciclosporin.


Combating head and neck cancer metastases by targeting Src using multifunctional nanoparticle-based saracatinib.
Inhibition of metastasis of head and neck squamous cell carcinoma (HNSCC) is one of the most important challenges in cancer treatment. Src, a non-receptor tyrosine kinase, has been implicated as a key promoter in tumor progression and metastasis of HNSCC. However, Src therapy for HNSCC is limited by lack of efficient in vivo delivery and underlying mechanisms remain elusive. Src knockdown cells were achieved by lentiviral-mediated interference. Cell migration and invasion were examined by wound healing and Transwell assays. Protein levels were determined by Western blot and/or immunohistochemistry. The Src inhibitor saracatinib was loaded into self-assembling nanoparticles by the solvent evaporation method. An experimental metastasis mouse model was generated to investigate the drug efficacy in metastasis. Blockade of Src kinase activity by saracatinib effectively suppressed invasion and metastasis of HNSCC. Mechanistic assessment of the drug effects in HNSCC cells showed that saracatinib induced suppression of Src-dependent invasion/metastasis through downregulating the expression levels of Vimentin and Snail proteins. In tests in mice, saracatinib loaded into the novel multifunctional nanoparticles exhibited superior effects on suppression of HNSCC metastasis compared with the free drug, which is mainly attributed to highly specific and efficient tumor-targeted drug delivery system. These findings and advances are of great importance to the development of Src-targeted nanomedicine as a more effective therapy for metastatic HNSCC.


Nuclear translocation controlled by alternatively spliced isoforms inactivates the QUAKING apoptotic inducer.
The quaking viable mice have myelination defects and develop a characteristic tremor 10 d after birth. The quaking gene encodes at least five alternatively spliced QUAKING (QKI) isoforms that differ in their C-terminal 8--30-amino-acid sequence. The reason for the existence of the different QKI isoforms and their function are unknown. Here we show that only one QKI isoform, QKI-7, can induce apoptosis in fibroblasts and primary rat oligodendrocytes. Heterodimerization of the QKI isoforms results in the nuclear translocation of QKI-7 and the suppression of apoptosis. The unique C-terminal 14 amino acids of QKI-7 confers the ability to induce apoptosis to heterologous proteins such as the green fluorescent protein and a QKI-related protein, Caenorhabditis elegans GLD-1. Thus, the unique C-terminal sequences of QKI-7 may function as a life-or-death 'sensor' that monitors the balance between the alternatively spliced QKI isoforms. Moreover, our findings suggest that nuclear translocation is a novel mechanism of inactivating apoptotic inducers.


[Endoscopic treatment of children with esophagus stenoses of different etiology].
Nowadays not only diagnostic but also therapeutic interventions are widely used in pediatric endoscopy. The authors analyze 25 cases of esophageal stenosis of different genesis (caustic, peptic, anastomotic and congenital esophageal obstructions) in children aged from 1.6 to 15 years. The endoscopic treatment was successfully performed by mechanical dilators with a guidewire and balloon dilator in all patients. The age less than 2 years, previous complications, subtotal stenosis can not be considered absolute contraindication for endoscopic treatment.


Stereotactic body radiotherapy for liver metastases.
The role for local ablative therapies in the management paradigm of oligometastatic liver disease is increasing. The evidence base supporting the use of stereotactic body radiotherapy for liver metastases has expanded rapidly over the past decade, showing high rates of local control with low associated toxicity. This review summarises the evidence base to date, discussing optimal patient selection, challenges involved with treatment delivery and optimal dose and fractionation. The reported toxicity associated with liver stereotactic body radiotherapy is presented, together with possible pitfalls in interpreting the response to treatment using standard imaging modalities. Finally, potential avenues for future research in this area are highlighted.


Rapidly progressive myositis as the sole manifestation of a concurrent gastric carcinoma.
Inflammatory myopathies including polymyositis and dermatomyositis are autoimmune disorders presenting with characteristic muscle weakness. These diseases, especially dermatomyositis, have a well-known association with a wide variety of neoplasms including lung, breast, ovary and colon cancers. Here we report the case of a 58-year-old man who presented with a 3-week history of myositis and was simultaneously diagnosed with gastric cancer.


Effects of acute L-carnitine supplementation on nitric oxide production and oxidative stress after exhaustive exercise in young soccer players.
The aim of this study was to investigate the effect of acute L-carnitine supplementation at two different doses on nitric oxide (NO) production and oxidative stress after exhaustive exercise. The subjects were 26 healthy males aged 17-19 years. Subjects were randomly divided into two groups of 13 each and received 3 or 4 g L-carnitine via a glass of fruit juice. After 1 h, the treadmill test was started at a speed of 8 km/h, afterwards increasing the speed 1 km/h every 3 min with a 1 min rest before every speed increase until exhaustion. Venous blood samples were collected again within 5 min following the exercise test. One week later, the test was repeated on the same athletes with placebo fluids. All subjects received a placebo via a glass of fruit juice. 1 h after the same exercise protocol mentioned above was performed and blood samples were drawn immediately. These plasma samples were used for measurement of nitrate-nitrite (NOx), which are known to be the stable end products of NO, TBARs as a lipid peroxidation indicator and an antioxidant glutathione (GSH) levels. The results of this study have shown that L-carnitine applied at a 3 g dose provides strong antioxidant action by increasing the GSH and NOx level and decreasing the TBARs level.


Pharmacogenomics: Current Actionable Variants.
Pharmacogenomics (PGx), one of the several tools of precision medicine, has been slowly implemented in the clinic during the past decades. This process generally starts with direct and indirect genotype-phenotype associations of gene variants and drug efficacy, or adverse drug reactions, followed by replication and validation studies. Institutional efforts led by the PGx Research Network, The PGx Knowledge Base, and The Clinical Pharmacogenetics Implementation Consortium, mine all available data for further validation or research in additional populations. This data mining gives rise to a detailed classification of over 200 druggene pairs which, with enough documentation, may become part of a publishable guideline to aid clinicians in drug selection and dosing using genetics. The US Food and Drug Administration utilizes these guidelines to issue warnings and recommendations for specific drugs and their cautioning serves clinicians and pharmacists worldwide. Here, we aim to discuss the steps of this process and list existing actionable drug-gene pairs. Moreover, we describe the current status of PGx knowledge in populations from Mexico for actionable variants on the 19 genes listed by present PGx guidelines affecting 47 drugs. Our review collects current allele frequency information for these actionable variants, lists gaps of PGx information for relevant markers, and highlights the importance of continuing PGx research in Native and Mestizo populations.


Revisiting blood transfusion preparedness: experience from the Bam earthquake response.
Blood transfusion plays a critical role in the provision of medical care for disasters due to man-made and natural hazards. Although the short-term increase in blood donations following national disasters is well-documented, some aspects of blood transfusion during disasters remain under study. The 2003 earthquake in Bam, Iran resulted in the death of >29,000 people and injured 23,000. In total, 108,985 blood units were donated, but only 21,347 units (23%) actually were distributed to hospitals around the country. Kerman Province, the site of the disaster, received 1,231 (1.3%) of the donated units in the first four days after the disaster. The Bam experience revealed crucial missteps in the development of a post-event strategy for blood product management, and led to the development of a detailed disaster preparedness and response plan that addresses issues of donation, distribution, communication, transportation, and coordination. The current plan requires the Iranian Blood Transfusion Organization to convene a disaster task force immediately as the main coordinator of all disaster preparedness and response activities.


Molecular Imaging of Retinal Endothelial Injury in Diabetic Animals.
Diabetic retinopathy is a leading cause of vision loss. There is a great need for early diagnosis prior to the occurrence of irreversible structural damages. Expression of endothelial adhesion molecules is observed before the onset of diabetic vascular damage; however, to date, these molecules cannot be visualized in vivo. To quantify the expression of endothelial surface molecules, we generated imaging probes that bind to ICAM-1. The α-ICAM-1 probes were characterized via flow cytometry under microfluidic conditions. Probes were systemically injected into normal and diabetic rats, and their adhesion in the retinal microvessels was visualized via confocal scanning laser ophthalmoscopy. Histology was performed to validate in vivo imaging results. Vascular pathologies were visualized using trypsin-digested retinal preparations. The α-ICAM-1 probes showed significantly higher adhesion to retinal microvessels in diabetic rats than in normal controls (P < 0.01), whereas binding of control probes did not differ between the two groups. Western blotting results showed higher ICAM-1 expression in retinas of T1D animals than in normal controls. Retinal endothelial ICAM-1 expression was observed via molecular imaging before markers of structural damage, such as pericyte ghosts and acellular capillaries. Results indicate that molecular imaging can be used to detect subtle changes in the diabetic retina prior to the occurrence of irreversible pathology. Thus, ICAM-1 could serve as a diagnostic target in patients with diabetes. This study provides a proof of principle for non-invasive subclinical diagnosis in experimental diabetic retinopathy. Further development of this technology could improve management of diabetic complications.


Predictors of poor health-related quality of life among people living with HIV aged ≥60 years in the PISCIS cohort: Findings from the Vive+ project.
Advancements in and accessibility to effective antiretroviral therapy has improved the life expectancy of people living with HIV, increasing the proportion of people living with HIV reaching older age (≥60 years), making this population's health-related quality of life (HRQoL) more relevant. Our aim was to identify the determinants of poor HRQoL in people living with HIV aged ≥60 years and compare them with those of their younger counterparts. We used data from the 'Vive+' study, a cross-sectional survey conducted between October 2019 and March 2020, nested within the PISCIS cohort of people living with HIV in Catalonia and the Balearic Islands, Spain. We used the 12-item short-form survey (SF-12), divided into a physical component summary (PCS) and a mental component summary (MCS), to evaluate HRQoL. We used the least absolute shrinkage and selection operator for variable selection and used multivariable regression models to identify predictors. Of the 1060 people living with HIV (78.6% males) who participated in the study, 209 (19.7%) were aged ≥60 years. When comparing older people living with HIV (≥60 years) and their younger counterparts, older people exhibited a worse PCS (median 51.3 [interquartile range {IQR} 46.0-58.1] vs. 46.43 [IQR 42.5-52.7], p < 0.001) but a similar MCS (median 56.0 [IQR 49.34-64.7] vs. 57.0 [IQR 48.9-66.3], p = 0.476). In the multivariable analysis, cognitive function correlated with a PCS (β correlation factor [β] -0.18, p = 0.014), and depressive symptoms and satisfaction with social role correlated with an MCS (β 0.61 and β -0.97, respectively, p < 0.001) in people living with HIV aged ≥60 years. Depressive symptoms, poor cognitive function, and lower satisfaction with social roles predict poorer HRQoL in older people living with HIV. These factors need to be considered when designing targeted interventions.


[Molecular biology of the germination of Bacillus spores].
The review deals with recent results and problems of gene expression during germination of Bacillus spores. Three problems were selected: 1. The activation of metabolism as a prerequisite for the synthesis of nucleic acids and proteins. 2. The activation of nucleic acid and protein synthesis during germination. 3. The gene expression programme of germinating spores. Using the highly sensitive two-dimensional polyacrylamide gel analysis three major classes of proteins were distinguished, depending on the time of onset and duration of their syntheses: a) proteins made throughout germination (main class), b) proteins whose synthesis started only after a lag phase and then continued throughout germination, and c) proteins which are synthesized only during the early phases of germination. The programme of protein synthesis is an indicator for the control of gene expression during germination. The regulation of expression of these major gene groups during spore outgrowth is discussed.


A comparison of several point estimators of the odds ratio in a single 2 x 2 contingency table.
The relative performance of the unconditioned maximum likelihood estimators (UMLEs), conditional MLEs (CMLEs), and Jewell-type estimators of the odds ratio (OR) and its logarithm were investigated in sets of single 2 x 2 contingency tables. The tables were generated by complete enumeration of all possible cell frequencies consistent with a single fixed margin. The bias, mean squared error (MSE), and average absolute error (AAE) were computed for all estimators using the individual table probabilities as weights. The results showed that, for the OR, Jewell's estimator usually had smaller bias, MSE, and AAE than either of the MLEs. While the differences were often slight for MSE and AAE, for bias it was sometimes substantial. For the log(OR), the UMLE usually had the lowest bias, and its MSE and AAE were only slightly greater than those for the other estimators. Overall, we recommend estimation on the log scale using the UMLE. If OR is to be estimated, Jewell's method had strong merit, although it is nonsymmetric with respect to the table orientation. In view of this, the UMLE may again be favoured in some situations.


Extracellular proteins of Cryptococcus neoformans and host antibody response.
Proteins secreted by the fungal pathogen Cryptococcus neoformans may be involved in invasion and could be useful in vaccine design. Despite the medical importance of this fungus, little is known about its extracellular proteins or the immune response to these antigens. To study C. neoformans extracellular proteins, 12 strains were metabolically radiolabeled and protein supernatants were analyzed. Both strain- and growth condition-dependent differences were observed. Enzymatic assays of filtered culture supernatants revealed butyrate esterase and caprylate esterase lipase activity for 11 of 12 strains, as well as acid phosphatase, naphthol-AS-BI-phosphohydrolase, and beta-glucosidase activities in some strains. Serum from infected rodents immunoprecipitated several secreted proteins, consistent with in vivo expression and development of an antibody response. For strain 24067, two immunodominant species, of approximately 75 and 30 kDa, were recognized. The relative intensity of the autoradiographic bands depended on the route of infection for both rats and mice. In summary, our results indicate that (i) there are multiple proteins in C. neoformans culture supernatants, (ii) there are strain differences in supernatant protein profiles, (iii) there are differences in supernatant protein profile depending on the growth conditions, (iv) there are several new extracellular and/or cell-associated enzymatic activities, and (v) antibodies to several supernatant proteins are made in the course of infection.


Neonatal outcome in women treated for the antiphospholipid syndrome during pregnancy.
The aim of this study was to determine the neonatal outcome in women with well-characterized antiphospholipid syndrome treated during pregnancy with low-dose aspirin. We compared 38 babies born after 36 pregnancies of 33 women diagnosed as having antiphospholipid syndrome with a group of 38 control infants matched for the same gestational age at birth. In all 76 newborns we studied the maternal events associated with the antiphospholipid syndrome, mothers' treatment and neonatal data. All mothers with antiphospholipid syndrome were treated with low-dense aspirin. Prednisone was only prescribed due to maternal complications and heparin in a case of thrombosis. No significant relation was found between maternal treatment and neonatal complications. The prematurity rate in these newborns was high 14% and the neonatal mortality (5.8%) was only associated with extreme prematurity (p < 0.001). In our population the overall rate of neonatal complications was higher than in the general population, but when compared with a similar group of newborns no significant differences were found. Our results suggest that primary antiphospholipid syndrome appears to be improved by low-dose aspirin treatment, with a high rate of neonatal survival (95%). Except for prematurity and its potential associated complications, fetal and neonatal outcome is very favourable and no significant relation between maternal treatment and neonatal pathology has been detected.


Hypothermic Oxygenated Perfusion Versus Normothermic Regional Perfusion in Liver Transplantation From Controlled Donation After Circulatory Death: First International Comparative Study.
To compare HOPE and NRP in liver transplantation from cDCD. Liver transplantation after cDCD is associated with higher rates of graft loss. Dynamic preservation strategies such as NRP and HOPE may offer safer use of cDCD grafts. Retrospective comparative cohort study assessing outcomes after cDCD liver transplantation in 1 Swiss (HOPE) and 6 French (NRP) centers. The primary endpoint was 1-year tumor-death censored graft and patient survival. A total of 132 and 93 liver grafts were transplanted after NRP and HOPE, respectively. NRP grafts were procured from younger donors (50 vs 61 years, P < 0.001), with shorter functional donor warm ischemia (22 vs 31 minutes, P < 0.001) and a lower overall predicted risk for graft loss (UK-DCD-risk score 6 vs 9 points, P < 0.001). One-year tumor-death censored graft and patient survival was 93% versus 86% (P = 0.125) and 95% versus 93% (P = 0.482) after NRP and HOPE, respectively. No differences in non-anastomotic biliary strictures, primary nonfunction and hepatic artery thrombosis were observed in the total cohort and in 32 vs. 32 propensity score-matched recipients CONCLUSION:: NRP and HOPE in cDCD achieved similar post-transplant recipient and graft survival rates exceeding 85% and comparable to the benchmark values observed in standard DBD liver transplantation. Grafts in the HOPE cohort were procured from older donors and had longer warm ischemia times, and consequently achieved higher utilization rates. Therefore, randomized controlled trials with intention-to-treat analysis are needed to further compare both preservation strategies, especially for high-risk donor-recipient combinations.


Causal inference in continuous time: an example on prostate cancer therapy.
In marginal structural models (MSMs), time is traditionally treated as a discrete parameter. In survival analysis on the other hand, we study processes that develop in continuous time. Therefore, Røysland (2011. A martingale approach to continuous-time marginal structural models. Bernoulli 17, 895-915) developed the continuous-time MSMs, along with continuous-time weights. The continuous-time weights are conceptually similar to the inverse probability weights that are used in discrete time MSMs. Here, we demonstrate that continuous-time MSMs may be used in practice. First, we briefly describe the causal model assumptions using counting process notation, and we suggest how causal effect estimates can be derived by calculating continuous-time weights. Then, we describe how additive hazard models can be used to find such effect estimates. Finally, we apply this strategy to compare medium to long-term differences between the two prostate cancer treatments radical prostatectomy and radiation therapy, using data from the Norwegian Cancer Registry. In contrast to the results of a naive analysis, we find that the marginal cumulative incidence of treatment failure is similar between the strategies, accounting for the competing risk of other death.


Measuring the effectiveness of nursing care.
Identification and measurement of the outcomes of nursing care have received great attention in the past decade. With advances in information technology, large clinical data bases are being developed for use in outcomes evaluation. It is important that nurses be thoughtful in designing the data elements that will be included in these data bases. Key data elements include nursing diagnoses, interventions, and nursing sensitive outcomes. Multiple variables influence the outcome of health care. It is important in evaluation that system, patient, and provider characteristics be considered, especially when developing benchmarks for comparison of outcome achievement. Data related to the process of care are needed beyond provider encounter, and nurses must be cautious that the care they give is not credited to other providers. Longitudinal clinical data bases that contain key variables related to the delivery of nursing care can yield valuable knowledge on the best methods to measure and interpret the contribution of nursing care to the health of the nation.


An alginate pick-up alternative to the altered cast technique.
The altered cast technique for distal extension removable partial dentures involves such cumbersome laboratory procedures that many dentists avoid using it. This article presents a simple and easy clinical technique that accomplishes the same objective, but involves no additional laboratory work. In addition, the technique provides superior accuracy when compared with the altered cast technique.


Exploring the barriers and facilitators to volunteering as an intervention for those with long-term neurological conditions: How make therapeutic volunteering possible?
Volunteering may have therapeutic benefits, but little is known about its requirements and potential for people with neurological conditions (pwNC). Two separate focus groups were conducted in Darmstadt, Germany: one group consisting of six pwNC and another group consisting of four health care professionals and three volunteering service providers. The focus groups were audio-recorded, transcribed and data were managed using NVivo12. The thematic analysis was applied. Four main themes were identified: (1) Impact of volunteering, (2) Individualisation, (3) Developmental space and (4) Funded supported volunteering. According to the findings, volunteering can be used as a strategy to enhance physical, mental and social well-being in disease management for people with long-term neurological conditions. Facilitators for accessibility of therapeutic volunteering; involvement of pwNC.


Acoustic cardiography S3 detection use in problematic subgroups and B-type natriuretic peptide "gray zone": secondary results from the Heart failure and Audicor technology for Rapid Diagnosis and Initial Treatment Multinational Investigation.
Dyspneic emergency department (ED) patients present a diagnostic dilemma. The S3, although highly specific for acute heart failure (AHF) and predicting death and readmission, is often difficult to auscultate. The HEart failure and Audicor technology for Rapid Diagnosis and Initial Treatment (HEARD-IT) multinational trial evaluated the S3 via acoustic cardiography (Audicor). Our goal in this secondary analysis was to determine if the strength of the S3 can provide diagnostic/prognostic information in problematic heart failure subgroups. Dyspneic ED patients older than 40 years and not on dialysis were prospectively enrolled. A gold standard AHF diagnosis was determined by 2 cardiologists blinded to acoustic cardiography results. The S3 strength parameter was delineated on a scale of 0 to 10. This secondary analysis of subgroups from the HEARD-IT database used univariate/multivariate regression to determine the diagnostic/prognostic ability of the S3 strength. In the 995 patients enrolled, S3 strength was a significant prognosticator in univariate analysis for adverse events but not in a multivariable model. In patients with "gray zone" B-type natriuretic peptide (BNP) levels (100-499 pg/mL), acoustic cardiography increased diagnostic accuracy of AHF from 47% to 69%. Acoustic cardiography improved S3 detection sensitivity in obese patients when compared to auscultation. The strength of the S3 gallop provides rapid results that assist with identification of AHF in selected populations. S3 detection complements the use of BNP in the gray zone, and its diagnostic/prognostic ability is largely unaffected by body mass index and renal function. S3 strength shows promise as a diagnostic and prognostic tool in problematic HF subgroups.


The global cardiovascular risk transition: associations of four metabolic risk factors with national income, urbanization, and Western diet in 1980 and 2008.
It is commonly assumed that cardiovascular disease risk factors are associated with affluence and Westernization. We investigated the associations of body mass index (BMI), fasting plasma glucose, systolic blood pressure, and serum total cholesterol with national income, Western diet, and, for BMI, urbanization in 1980 and 2008. Country-level risk factor estimates for 199 countries between 1980 and 2008 were from a previous systematic analysis of population-based data. We analyzed the associations between risk factors and per capita national income, a measure of Western diet, and, for BMI, the percentage of the population living in urban areas. In 1980, there was a positive association between national income and population mean BMI, systolic blood pressure, and total cholesterol. By 2008, the slope of the association between national income and systolic blood pressure became negative for women and zero for men. Total cholesterol was associated with national income and Western diet in both 1980 and 2008. In 1980, BMI rose with national income and then flattened at ≈Int$7000; by 2008, the relationship resembled an inverted U for women, peaking at middle-income levels. BMI had a positive relationship with the percentage of urban population in both 1980 and 2008. Fasting plasma glucose had weaker associations with these country macro characteristics, but it was positively associated with BMI. The changing associations of metabolic risk factors with macroeconomic variables indicate that there will be a global pandemic of hyperglycemia and diabetes mellitus, together with high blood pressure in low-income countries, unless effective lifestyle and pharmacological interventions are implemented.


[A cytofluorimetric study of the stability of the DNA secondary structure in the epithelial cells of adenocarcinomas of the large intestine].
Investigation was carried out on the epithelial cells obtained from 32 patients with benign and malignant tumors of large intestine aged from 42 to 80 years. Ratio of single-stranded and double-stranded DNAs in the epithelial cells of unchanged colorectal mucosa (12 patterns), adenomatous polyps (4) and adenocarcinomas (29) was studied using fluorimetric analysis. Increased instability of DNA secondary structure was revealed in the tumor cells comparing to the cells of unchanged colorectal epithelium. Relative accumulation of single-stranded DNA reflects structural and functional changes in gene apparatus of cells under malignization.


Increasing value and reducing waste in research design, conduct, and analysis.
Correctable weaknesses in the design, conduct, and analysis of biomedical and public health research studies can produce misleading results and waste valuable resources. Small effects can be difficult to distinguish from bias introduced by study design and analyses. An absence of detailed written protocols and poor documentation of research is common. Information obtained might not be useful or important, and statistical precision or power is often too low or used in a misleading way. Insufficient consideration might be given to both previous and continuing studies. Arbitrary choice of analyses and an overemphasis on random extremes might affect the reported findings. Several problems relate to the research workforce, including failure to involve experienced statisticians and methodologists, failure to train clinical researchers and laboratory scientists in research methods and design, and the involvement of stakeholders with conflicts of interest. Inadequate emphasis is placed on recording of research decisions and on reproducibility of research. Finally, reward systems incentivise quantity more than quality, and novelty more than reliability. We propose potential solutions for these problems, including improvements in protocols and documentation, consideration of evidence from studies in progress, standardisation of research efforts, optimisation and training of an experienced and non-conflicted scientific workforce, and reconsideration of scientific reward systems.


Telephone reminders to reduce non-attendance rate for endoscopy.
Non-attendance at clinics and endoscopy units wastes resources and lengthens waiting lists. In a previous study elsewhere, a substantial proportion of patients claimed to have forgotten their appointment. We therefore assessed the value of telephoning patients a week before their booked day-case endoscopy. An observation period of two months was followed by an intervention period of two months in which patients were contacted by phone and asked if they wished to come for their investigation. A maximum of three separate attempts were made to contact each patient. Patients cancelling the appointment were replaced by others on the reserve list. The non-attendance rate was expressed as the percentage of unused beds. During the observation period 56 patients were admitted and 18 beds were unused. During the intervention period it was possible to contact 73 of 88 patients and 8 of these cancelled. 87 beds were available and 83 patients were admitted. When clerical error, overbooking and failure to replace patients were taken into account, the non-attendance rate declined from 23.3% during the observation period to 5.7% during the intervention period (P<0.05). The intervention seemed more effective in reducing non-attendance in outpatients referrals (0/48) than in general practitioner referrals (5/40).


Structure of the Alk1 extracellular domain and characterization of its bone morphogenetic protein (BMP) binding properties.
Bone morphogenetic proteins (BMPs) are secreted signaling proteins - they transduce their signals by assembling complexes comprised of one of three known type II receptors and one of four known type I receptors. BMP-9 binds and signals through the type I receptor Alk1, but not other Alks, while BMP-2, -4, and -7 bind and signal through Alk3, and the close homologue Alk6, but not Alk1. The present results, which include the determination of the Alk1 structure using NMR and identification of residues important for binding using SPR, show that the β-strand framework of Alk1 is highly similar to Alk3, yet there are significant differences in loops shown previously to be important for binding. The most pronounced difference is in the N-terminal portion of the β4-β5 loop, which is structurally ordered and includes a similarly placed but shorter helix in Alk1 compared to Alk3. The altered conformation of the β4-β5 loop, and to lesser extent β1-β2 loop, cause clashes when Alk1 is positioned onto BMP-9 in the manner that Alk3 is positioned onto BMP-2. This necessitates an alternative manner of binding, which is supported by a model of the BMP-9/Alk1 complex constructed using the program RosettaDock. The model shows that Alk1 is positioned similar to Alk3 but is rotated by 40 deg. The alternate positioning allows Alk1 to bind BMP-9 through a large hydrophobic interface, consistent with mutational analysis that identified several residues in the central portion of the β4-β5 loop that contribute significantly to binding and are nonconservatively substituted relative to the corresponding residues in Alk3.


Pricing of Shanghai stock exchange 50 ETF options based on different volatility models.
On March 15, 2022, the volume of trade of the Shanghai Stock Exchange (SSE) 50 ETF option contracts and the CSI 300 ETF option contracts exceeded 10 million for the first time, of which 5,707,400 50 ETF options were traded, and SSE 50 ETF options, as the main force, has become one of the most active ETF option varieties in the world after seven years of vigorous development. The SSE 50 ETF options receive highlights in risk-free arbitrage, hedging, risk management and other aspects. In order to give full play to the function of the SSE 50 ETF options, it is necessary to conduct studies on their pricing. This paper adopts the traditional classical models for pricing European-style options, the BSM model and the volatility model, to price call options and put options of the SSE ETF, and meanwhile analyzes the volatility of the SSE 50 ETF. The empirical results suggest that (1) the volatility of SSE 50 ETF has a weak leverage effect or no leverage effect, which converges with the existence of the inverse leverage effect of the SSE index; (2) the BSM model will underestimate the price of SSE 50 ETF options and is only ideal for pricing in-the-money (ITM) options; while out-of-the-money (OTM) options are highly influenced by time value and therefore cannot be accurately priced.


Solar p-Mode Eigenfrequencies Are Decreased by Turbulent Convection.
Average solar p-mode eigenfrequencies are decreased by large fluctuating velocity fields in the upper convection zone. This effect is greatest for modes with large horizontal wave numbers and frequencies. It is large enough to affect estimates of the depth of the convection zone and may carry useful information about the structure of solar convective turbulence.


Intraprocedural direct left atrial and wedge pressure correlation during transcatheter mitral valve repair: Results from a single center registry.
This study investigates the correlation of occlusive wedge pressure (WP) with direct left atrial (LA) pressure in patients with severe mitral regurgitation (MR) undergoing transcatheter mitral valve repair (TMVr) with MitraClip. There is interest in acquiring objective hemodynamic parameters for intraprocedural guidance in patients undergoing MitraClip. The study included 94 patients with severe MR at prohibitive surgical risk who underwent MitraClip at the University of California Davis Medical Center between 2014 and 2016. An average of 1.8 ± 0.7 clips were used to achieve MR grade of 2+ or less in 99% of patients. Correlation analysis of all (n = 236) pre-clip, inter-clip, and final-clip WP and LA pressures yielded a Pearson's R (r) of 0.85 and 0.79 for mean WP vs mean LA and WP V vs LA V, respectively. Median LA V to mean LA ratio (LAV:mLA) was 1.75 (IQR 1.5-1.9). 79% (n = 74) of patients had LAV:mLA ratio ≥ 1.5 with associated WP V vs LA V correlation (r) of 0.83. In patients with LAV:mLA ratio < 1.5, the correlation (r) was 0.69. Baseline characteristics were not significantly different between patients with LAV:mLA ratio ≥ 1.5 and patients with LAV:mLA ratio < 1.5. Post-procedure, median LA V: mean LA ratio decreased from 1.75 to 1.4, P = 0.0001. Correlation between WP and direct LA pressure in patients with severe MR undergoing Mitraclip is modest. Caution is advised when using WP to approximate LA pressure intraprocedurally, especially in patients with baseline low LAV:mLA ratios.


Evolution of ophthalmic and electrophysiological findings in identical twin sisters with the carbohydrate deficient glycoprotein syndrome type 1 over a period of 14 years.
To evaluate the evolution of ocular and electroretinographic findings in identical twin sisters with the carbohydrate deficient glycoprotein (CDG) syndrome over a period of 14 years. Both girls underwent a clinical ophthalmic examination with funduscopy and an electrophysiological assessment with recording of flash electroretinogram (FERG) at the age of 4 years and 18 years On ophthalmic examination at the age of 4 years an alternating convergent squint and a saccadic pursuit was diagnosed. In both, vision was 6/9 bilaterally. Fundus examination showed normal optic discs, narrow blood vessels, and a mild irregular pigmentation in the periphery. In one girl the FERG showed a recognisable a, b1, and b2-wave with reduced amplitude to less than 40% of the normal. In the other girl the reduction in amplitude was still more obvious, but for the white flash a small b1-wave was still present. At the age of 18 vision had remained 6/9 in both eyes. Funduscopy showed pink optic discs, moderately narrowed blood vessels, and bony spicule pigmentary deposits in the mid periphery. The adapto ERG, performed in identical conditions at 18 years of age, showed a completely extinguished trace for both eyes. Despite progressive deterioration of ERG findings good central vision was preserved over 14 years.


Cerebral Perfusion and the Occurrence of Nonfocal Transient Neurological Attacks.
Nonfocal transient neurological attacks (TNAs) are associated with an increased risk of cardiac events, stroke and dementia. Their etiology is still unknown. Global cerebral hypoperfusion has been suggested to play a role in their etiology, but this has not been investigated. We assessed whether lower total brain perfusion is associated with a higher occurrence of TNAs. Between 2015 and 2018, patients with heart failure were included in the Heart Brain Connection study. Patients underwent brain magnetic resonance imaging, including quantitative magnetic resonance angiography (QMRA) to measure cerebral blood flow (CBF). We calculated total brain perfusion of each participant by dividing total CBF by brain volume. Patients were interviewed with a standardized questionnaire on the occurrence of TNAs by physicians who were blinded to QMRA flow status. We assessed the relation between total brain perfusion and the occurrence of TNAs with Poisson regression analysis. Of 136 patients (mean age 70 years, 68% men), 29 (21%) experienced ≥1 TNAs. Nonrotatory dizziness was the most common subtype of TNA. Patients with TNAs were more often female and more often had angina pectoris than patients without TNAs, but total CBF and total brain perfusion were not different between both groups. Total brain perfusion was not associated with the occurrence of TNAs (adjusted risk ratio 1.12, 95% CI 0.88-1.42). We found no association between total brain perfusion and the occurrence of TNAs in patients with heart failure.


Perioperative Care of a Child With Cri Du Chat Syndrome.
Cri du chat syndrome (CdCS) is a chromosomal disorder resulting from a deletion in the short arm of chromosome 5. Anatomical abnormalities of the larynx result in a distinctive high-pitched, cat-like cry for which the disorder is named. Typical findings of the syndrome involve the upper airway, cardiovascular, and central nervous system (CNS). Of particular concern during anesthetic care is the potential for airway abnormalities leading to difficulties with endotracheal intubation as well as the presence of congenital heart disease (CHD). We present a 15-month-old child with CdCS who required anesthetic care during direct laryngoscopy and supraglottoplasty. The perioperative concerns of such patients are discussed, and previous reports of anesthetic care reviewed.


[Role of tricyclic antidepressants in the central regulation of hyperalgesia and stress analgesia].
The effect of hypophysectomy (HE) on pain thresholds was studied in female noninbred rats. Hyperalgesia was observed after HE since the first till the sixth day of the observation period. Droperidol (1 mg/kg i.p.) and amitryptyline (5 mg/kg i.p.) produced hyperalgesia in sham-operated rats, which was potentiated in hypophysectomized animals. In rats taken into the experiment 3 days after operation, no increase in the pain threshold was recordable during the 30-minute painful stress, and poststress autoanalgesia did not develop subsequently. The opposing data were obtained in sham-operated animals. On intraperitoneal administration of phentanyl (25 micrograms/kg) after the 30-minute painful stress hypophysectomized rats did not manifest any potentiation of its analgesic effect in contradistinction to sham-operated animals. Simultaneous administration of phentanyl at the same dose and melipramine (5 mg/kg i.p.) produced considerable potentiation of analgesia if administered after stress. In hypophysectomized rats, that effect was somewhat reduced.


Interplay between group size, huddling behavior and basal metabolism: an experimental approach in the social degu.
Mammals exposed to low temperatures increase their metabolic rate to maintain constant body temperature and thus compensate for heat loss. This high and costly energetic demand can be mitigated through thermoregulatory behavior such as social grouping or huddling, which helps to decrease metabolic rate as function of the numbers of individuals grouped. Sustained low temperatures in endothermic animals produce changes over time in rates of energy expenditure, by means of phenotypic plasticity. However, the putative modulating effect that huddling exerts on the flexibility of the basal metabolic rate (BMR) due to thermal acclimation remains unknown. We determined BMR values in Octodon degus, an endemic Chilean rodent, after being acclimated to either 15 or 30°C during 60 days, both alone and in groups of three and five individuals. At 15°C, BMR of huddling individuals was 40% lower than that of animals housed alone. Moreover, infrared thermography revealed a significant increase in local surface temperatures in huddled animals. Furthermore, individual thermal conductance was lower in individuals acclimated to 15°C than to 30°C, but no differences were observed between single and grouped animals. Our results indicate that huddling prevents an increase in BMR when animals are acclimated to cold conditions and that this effect is proportional to the number of animals grouped.


Simulation of roller compaction with subsequent tableting and characterization of lactose and microcrystalline cellulose.
Tablets are by far the most common solid oral dosage forms, and many drugs need to be granulated before they can be tableted. Increasingly roller compaction is being used as a dry granulation technique; however it is a very time and material intensive method. Thus some mini roller compactors and simulations of the roller compaction process have been developed as a means of studying the technique at small scale. An important factor in the selection of materials for roller compaction is their ability to be recompressed into tablets after the initial roller compaction and milling steps. In this paper the roller compaction process was simulated on the basis of some models by Gereg and Cappola (2002) and Zinchuk et al. (2004). An eccentric tableting machine was used to make compacts from alpha-lactose monohydrate, anhydrous beta-lactose, spray-dried lactose and microcrystalline cellulose at different maximum relative densities (rho rel,max 0.6-0.9). These compacts were milled immediately to granules with a rotary granulator. The properties of the granules were analyzed and compared to the properties of the original powders. These granules and powders were then tableted at different maximum relative densities (rho rel,max 0.75-0.95) and their properties including elastic recovery, crushing force and 3D-model were analyzed. The properties of the tablets made from the granules were compared to the properties of the tablets made from the powders to determine which excipients are most suitable for the roller compaction process. The study showed that anhydrous beta-lactose is the preferred form of lactose for use in roller compaction since compaction did not affect tablet crushing force to a large extent. With the simulation of roller compaction process one is able to find qualified materials for use in roller compaction without the necessity of a great deal of material and time.


[Bladder paraganglioma. Report of a case and review of the Spanish literature].
Paragangliomas are rare tumours of the bladder accounting for 0.06% of all vesical tumours. This paper reports one case of vesical paraganglioma in a young female patient that has the singularity of being associated to melanin pigmentation. A review is made of cases treated in Spain, adding some comments on the signs and symptoms presented, as well as the diagnostic and therapeutical methods used in this unusual condition.


Hepatotoxicity in Obese Versus Nonobese Patients With Acetaminophen Poisoning Who Are Treated With Intravenous N-Acetylcysteine.
There is limited information regarding the outcomes associated with acetaminophen (APAP) poisoning in obese individuals. It is possible that patients who are obese are more susceptible to APAP-induced liver injury, thereby diminishing the efficacy of antidotes such as N-acetylcysteine (NAC). We evaluated the outcomes associated with APAP poisoning in obese versus nonobese adults who are treated with intravenous (IV) NAC. This was a retrospective cohort study conducted in a tertiary care, academic medical center. Adult patients with APAP toxicity, who were treated with IV NAC between June 2005 and August 2012, were included. The patients were categorized into 2 groups based on their body mass index (BMI): (1) obese (BMI ≥ 30.0 kg/m) versus (2) nonobese (BMI 18.5-24.9 kg/m). The primary outcome measure was the proportion of patients who developed hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >1000 IU/L). A total of 80 patients were included in the final cohort (40 in each group). The median BMI for the obese and nonobese groups was 34.5 kg/m [interquartile range (IQR) 31.4-40.2] and 22.4 kg/m (IQR 21.2-23.9), respectively (P < 0.001). Other than more white patients being present in the nonobese group, there were no other baseline differences between groups with regard to demographics, liver function tests, or coagulation studies. Obese patients received a median IV NAC dose of 291.5 mg/kg (IQR 270.8-300.7) compared with 300 mg/kg (IQR 287.8-301.9) in the nonobese group (P = 0.07). Hepatotoxicity occurred in 27.5% of the obese patients and 37.5% of the nonobese patients (P = 0.34). No adverse drug effects were noted in either group. Obese and nonobese patients being treated with IV NAC for APAP toxicity experienced similar rates of hepatotoxicity.


Na+-K+ pump in chronic renal failure.
This review summarizes the evidence for the defect in Na+-K+ pump in chronic renal failure, considers the role of various factors in causing this defect, and discusses the clinical implications thereof. Intracellular Na is elevated in erythrocytes, leukocytes, and muscle cells from some patients with chronic renal failure (CRF). Recent evidence suggests that this elevation of cell Na may be, in large part, a consequence of decreased number of Na+-K+ pump units per cell. Maintenance dialysis over a period of weeks ameliorates the defect in intracellular Na+, and this improvement is contemporaneous with an increase in the number of Na+-K+ pump sites per cell. In erythrocytes with normal cell Na+, acute hemodialysis increases the rate of Na+ and K+ transport. Many factors such as the presence of retained toxic metabolite or circulating inhibitor in the uremic plasma, or biochemical changes produced by acute hemodialysis, may explain this finding. In cells with high cell Na+, the pump-mediated K+ transport is normalized at the expense of a raised cell Na+. The decreased muscle membrane potential in uremic subjects has been attributed to a decreased activity of Na+-K+ pump. Enzymatic Na+-K+-ATPase activity of the uremic erythrocyte, leukocyte, sarcolemma, and intestines is also decreased. We discuss the role of hormonal abnormalities and circulating inhibitors, which may cause an acute inhibition of the pump and of other factors such as K+ depletion, which may cause more chronic alterations. The implications of alteration of Na+ and K+ pump transport and raised cell Na+ on other non-pump-mediated transport pathways are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation of Novel Metrics of Symptom Relief in Acute Heart Failure: The Worst Symptom Score.
To characterize a novel "worst"-symptom visual analogue scale (WS-VAS) versus the traditional dyspnea visual analogue scale (DVAS) in an acute heart failure (AHF) trial. AHF trials assess symptom relief as a pivotal endpoint with the use of dyspnea scores. However, many AHF patients' worst presenting symptom (WS) may not be dyspnea. We hypothesized that a WS-VAS may reflect clinical improvement better than DVAS in AHF. AHF patients (n = 232) enrolled in the Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE-AHF) Trial indicated their WS at enrollment and completed DVAS and WS-VAS at enrollment and 24, 48, and 72 hours. Dyspnea was the WS in 61%, body swelling in 29%, and fatigue in 10% of patients. Clinical characteristics differed by WS. In all patients, DVAS scores were higher (less severe symptoms) than WS-VAS and the change in WS-VAS over 72 hours was greater than the change in DVAS (P < .001). Changes in DVAS were smaller in patients with body swelling and fatigue than in patients with dyspnea as their WS (P = .002), whereas changes in the WS-VAS were similar regardless of patients' WS. Neither score, nor its change, was associated with available decongestion markers (change in N-terminal pro-B-type natriuretic peptide, weight or cumulative 72-hour urine volume). Many AHF patients have symptoms other than dyspnea as their most bothersome symptom. The WS-VAS better reflects symptom improvement across the spectrum of AHF phenotypes. Symptom relief and decongestion were not correlated in this AHF study.


[Postoperative autotransfusion in primary knee replacement surgery].
To assess the efficacy of postoperative autologous transfusion to reduce homologous blood transfusion needs in primary knee replacement surgery. A prospective study was carried out in 33 consecutive patients with diagnoses of arthrosis scheduled for primary knee replacement surgery with postoperative autotransfusion using a CBCII Constavac-Stryker (Stryker Instruments, Michigan, USA) recovery system from June through October 2002. We analyzed patient age, sex, preoperative and postoperative (24 hours) hemoglobin and hematocrit values, autologous blood reinfused and homologous blood transfusion incidence rate (if hematocrit was below 25%). Of the 33 patients receiving postoperative autotransfusion, one also needed homologous blood transfusion (3%). The mean volume of filtered whole blood reinfused was 538.63+/-261.23 mL, 1100 mL being the largest volume reinfused. We observed no complications related to use of autotransfusion devices during the perioperative period. Postoperative autotransfusion as the only blood salvage technique in primary knee prosthesis surgery nearly eliminates homologous transfusion needs. In addition, it is a safe, simple procedure and has replaced our hospital's preoperative autologous transfusion procedure.


Patient alliance with the program predicts treatment outcomes whereas alliance with the therapist predicts adherence in internet-based therapy for panic disorder.
This study examines relationships among different aspects of therapeutic alliance with treatment outcome, adherence and attrition in internet delivered cognitive behavioral therapy (ICBT) for panic disorder. We examined alliance-outcome relationships in ICBT (N = 74) using a newly developed self-report alliance measure that disentangles alliance with program content (Internet Patient's Experience of Attunement and Responsiveness with the program; I-PEARp) and with the therapist (I-PEARt). We compared ICBT outcomes of patient rated and therapist-rated alliance with conventional alliance scales (WAI-6 and WAI-T). Consistent with our hypothesis, I-PEARp and I-PEARt distinguished between different aspects of the alliance and predicted outcomes better than standard alliance scales. Furthermore, higher ratings of I-PEARp were associated with subsequent lower symptoms and lower symptoms were associated with higher subsequent alliance. In contrast, I-PEARt predicted adherence, but not symptoms. Although therapists' ratings of alliance (thI-PEAR) improved significantly during treatment, they did not predict subsequent symptoms, adherence, or dropout. Results indicate that the patient experience of the alliance in ICBT includes two aspects, each of which uniquely contributes to outcomes; patient connection to the program is related to symptom outcomes whereas the dyadic relationship with the therapist serves as the glue to allow the treatment to hold.


Gaussian model of explosive percolation in three and higher dimensions.
The Gaussian model of discontinuous percolation, recently introduced by Araújo and Herrmann [Phys. Rev. Lett. 105, 035701 (2010)], is numerically investigated in three dimensions, disclosing a discontinuous transition. For the simple cubic lattice, in the thermodynamic limit we report a finite jump of the order parameter J=0.415±0.005. The largest cluster at the threshold is compact, but its external perimeter is fractal with fractal dimension d(A)=2.5±0.2. The study is extended to hypercubic lattices up to six dimensions and to the mean-field limit (infinite dimension). We find that, in all considered dimensions, the percolation transition is discontinuous. The value of the jump in the order parameter, the maximum of the second moment, and the percolation threshold are analyzed, revealing interesting features of the transition and corroborating its discontinuous nature in all considered dimensions. We also show that the fractal dimension of the external perimeter, for any dimension, is consistent with the one from bridge percolation and establish a lower bound for the percolation threshold of discontinuous models with a finite number of clusters at the threshold.


Quality improvement in acute stroke: the New York State Stroke Center Designation Project.
Many hospitals lack the infrastructure required to treat patients with acute stroke. The Brain Attack Coalition (BAC) published guidelines for the establishment of primary stroke centers. To determine if stroke center designation and selective triage of acute stroke patients improve quality of care. Baseline chart abstraction was performed on all stroke patients admitted to 32 hospitals serving Brooklyn and Queens, NY, from March to May 2002. Hospitals were invited to meet BAC guideline-based criteria. Adherence was verified by on-site visits. After designation, acute stroke patients were selectively triaged. Remeasurement data were collected from August to October 2003. The authors abstracted 1,598 charts at baseline and 1,442 charts at remeasurement. From baseline to remeasurement, median times decreased for door to physician contact (25 vs 15 minutes, p = 0.001), CT performance for potential tissue plasminogen activator (t-PA) candidates (68 vs 32 minutes, p < 0.001), and t-PA administration (109 vs 98 minutes (p = NS). IV t-PA utilization increased from 2.4 to 5.2% (p < 0.005), select t-PA protocol violations decreased from 11.1 to 7.9% (p = NS), and the stroke unit admission rate increased from 16 to 39% (p < 0.001). In stroke centers (n = 14) vs nondesignated hospitals (n = 18), there were shorter median times from door to physician contact (10 vs 25 minutes, p < 0.001), CT performance for potential t-PA candidates (31 vs 40 minutes, p = NS), and t-PA administration (95 vs 115 minutes, p < 0.05). Stroke centers, compared with nondesignated centers, admitted acute stroke patients to stroke units more often (55.9 vs 10.9%, p < 0.001). Stroke center designation and selective triage of acute stroke patients improved the quality of care, including access to timely thrombolytic therapy and stroke units.


Basic ocular pharmacotherapy.
1. There are certain unique features of pharmacotherapy as it relates to the eye. One is that we have the ability to apply a drug directly to the surface of the eye in the form of eyedrops. This has important ramifications in terms of pharmacokinetics, the distribution of drug throughout the ocular tissues. 2. Ocular pharmacokinetics is the study of the distribution of a drug over time. One of the principles of pharmacotherapy is that we want to maximize the amount of drug that reaches the site of action in a sufficient concentration to cause a beneficial therapeutic effect. 3. Ophthalmic nurses play an important role in patient education, because they spend time talking to patients about the proper way to use drugs.


Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside.
The coupling between arterial elastance (E(A); net afterload) and left ventricular elastance (E(LV); pump performance), known as E(A)/E(LV), is a key determinant of cardiovascular performance and shifts during exercise due to a greater increase in E(LV) versus E(A). This normal exercise-induced reduction in E(A)/E(LV) decreases with advancing age. We hypothesized that sodium nitroprusside (SNP) can acutely ameliorate the age-associated deficits in E(A)/E(LV). At rest and during graded exercise to exhaustion, E(A) was characterized as end-systolic pressure/stroke volume and E(LV) as end-systolic pressure/end-systolic volume. Resting E(A)/E(LV) did not differ between old (70 ± 8 yr, n = 15) and young (30 ± 5 yr, n = 17) subjects because of a tandem increase in E(A) and E(LV) in older subjects. During peak exercise, a blunted increase in E(LV) in old (7.8 ± 3.1 mmHg/ml) versus young (11.4 ± 6.5 mmHg/ml) subjects blunted the normal exercise-induced decline in E(A)/E(LV) in old (0.25 ± 0.11) versus young (0.16 ± 0.05) subjects. SNP administration to older subjects lowered resting E(A)/E(LV) by 31% via a reduction in E(A) (10%) and an increase in E(LV) (47%) and lowered peak exercise E(A)/E(LV) (36%) via an increase in E(LV) (68%) without a change in E(A). Importantly, SNP attenuated the age-associated deficits in E(A)/E(LV) and E(LV) during exercise, and at peak exercise E(A)/E(LV) in older subjects on drug administration did not differ from young subjects without drug administration. In conclusion, some age-associated deficiencies in E(A)/E(LV), E(A), and E(LV), in older subjects can be acutely abolished by SNP infusion. This is relevant to common conditions in older subjects associated with a significant impairment of exercise performance such as frailty or heart failure with preserved ejection fraction.


Longer time interval between completion of neoadjuvant chemoradiation and surgical resection does not improve downstaging of rectal carcinoma.
An interval of six to eight weeks between completion of preoperative chemoradiation therapy and surgical resection of advanced rectal cancer has been described. Our purpose was to determine whether a longer time interval between completion of therapy and resection increases tumor downstaging and affects perioperative morbidity. Forty patients with advanced adenocarcinoma of the rectum underwent preoperative chemoradiation on a prospective trial with irinotecan (50 mg/m2), 5-fluorouracil (225 mg/m2), and concomitant external-beam radiation (45-54 Gy) followed by complete surgical resection of the tumor with total mesorectal excision. The time interval between completion of chemoradiation and surgical resection ranged from 28 to 97 days. The patients were divided into two groups with 33 eligible patients: Group A (4-week to 8-week time interval; 28-56 days) and Group B (10-week to 14-week interval; 67-97 days). Tumor downstaging was compared between these two groups. The number of patients downstaged by at least one T stage, those downstaged by at least one N stage, those with pathologic complete responses, and those with only residual microscopic tumor foci were compared. Postoperative length of stay, estimated blood loss, perioperative morbidity, and sphincter-sparing procedures were also compared. Chi-squared tests and Student's t-test were calculated. Group A had 19 patients, and Group B had 14 patients. Patient demographics were comparable. Mean age was 52 years, and 70 percent of patients were male. There were no deaths. There were no statistical differences in perioperative morbidity, with three anastomotic leaks in Group A. Tumors were downstaged in 58 percent of patients in Group A and 43 percent of those in Group B (P = 0.61). Nodal downstaging occurred in 78 percent of Group A and 67 percent of Group B (P = 0.9). The pathologic complete response rate was 21 percent in Group A and 14 percent in Group B (P = 0.97), and a residual microfocus of tumor was found in 33 percent of patients in Group A and 42 percent of those in Group B (P = 0.90). These differences were not statistically significant. Perioperative morbidity is not affected by longer intervals. A longer interval between completion of neoadjuvant chemoradiation and surgical resection may not increase the tumor response rate of advanced rectal cancer in this cohort.


Ecology and evolution of antibiotic resistance.
The evolution of bacterial pathogens towards antibiotic resistance is not just a relevant problem for human health, but a fascinating example of evolution that can be studied in real time as well. Although most antibiotics are natural compounds produced by environmental microbiota, exposure of bacterial populations to high concentrations of these compounds as the consequence of their introduction for human therapy (and later on for farming) a few decades ago is a very recent situation in evolutionary terms. Resistance genes are originated in environmental bacteria, where they have evolved for millions of years to play different functions that include detoxification, signal trafficking or metabolic functions among others. However, as the consequence of the strong selective pressure exerted by antimicrobials at clinical settings, farms and antibiotic-contaminated natural ecosystems, the selective forces driving the evolution of these potential resistance determinants have changed in the last few decades. Natural ecosystems contain a large number of potential resistance genes; nevertheless, just a few of them are currently present in gene-transfer units and disseminated among pathogens. Along the review, the processes implied in this situation and the consequences for the future evolution of resistance and the environmental microbiota are discussed.


An analysis of pain and analgesia after Mohs micrographic surgery.
Pain characteristics and analgesia in patients undergoing Mohs micrographic surgery have not been systematically studied. It is important to know about pain after Mohs micrographic surgery to better serve patient needs. We sought to measure pain in patients after Mohs micrographic surgery, and to investigate the relationship among postoperative pain, surgical characteristics, patient characteristics, and analgesics used. The Wong-Baker 0-to-10 pain scale was prospectively administered postoperatively to all patients presenting for Mohs micrographic surgery in a private practice setting between October 1, 2007, and December 31, 2008. Patients recorded their pain level from the day of surgery through postoperative day 4. The age, sex, location of surgery, number of lesions operated on, postoperative size, type of repair, severity of pain, and oral analgesics consumed and dosages used were recorded. A total of 433 patients were included in the final analysis. The highest pain scores were found on the day of surgery and steadily declined until postoperative day 4 (P < .000). In all, 52% of patients took pain medication on the day of surgery, which declined successively with each postoperative day. The highest mean pain scores were statistically significantly associated with repair type (flaps), age (<66 years), number of lesions, and consumption of narcotics for pain relief. No statistically significant differences existed for sex or postoperative defect size. The instrument used to measure pain relied on patient self-report in a private practice surgery center. Only the validated Wong-Baker pain scale was used to assess pain in this study. Approximately half of the patients after Mohs micrographic surgery take medication for pain control. Type of closure, location of surgery, age, and type of pain medication taken were significantly associated with postoperative pain.


[The economic expenses related to bronchial asthma morbidity].
Estimations of the cost of bronchial asthma treatment per 1 patient in Samara Province made up an annual average of 520 dollars and 531 dollars in 1993 and 1994, respectively. 70% of the expenditures were medical, 30% social. It is demonstrated that updated approaches to diagnosis and treatment of asthma unless the patients are noncompliant provided good results at reduced expenses. The economic-mathematical model is proposed basing on which one can predict prevalence of bronchial asthma, cost-effect treatment relations for 5 years to come. The model reflects both current and forthcoming trends in care for bronchial asthma.


Entrance of cholera enterotoxin subunits into cells.
Quantitative analysis of the staining of cholera enterotoxin on the surface of cells with specific antibodies against each subunit of cholera toxin, using a Fluorescence-Activated Cell Sorter, showed that not only subunit A but also subunit B penetrates the cell membrane. The detection of each subunit inside the cell was facilitated by the use of saponin, an agent which increases membrane permeability.


The epidemiology of alcohol burns at a major burn centre in North China.
This study was designed to explore the epidemiological characteristics and potential preventive strategies of alcohol burns. In this five-year, retrospective study, 163 patients with alcohol burns (admitted from 1 January 2015 to 31 May 2020 were included. There was a male-to-female ratio of 1.1:1, a mean age of 34.1±16.8 years, and a mean burn size of 13.3±13.7% total body surface area (TBSA). The number of patients with alcohol burns was similar year by year during the five-year period. Just over half of patients (n=84, 51.5%) sustained a third-degree burn injury, which was significantly associated with a longer hospital stay and the need for surgery. The most prevalent aetiology was cupping (n=49, 29.5%), followed by cooking hotpot (n=37, 22.7%). Of the patients, seven (4.29%) sustained injuries during experiments at school and one patient sustained injury when using alcohol spray for disinfection against COVID-19. The incidence of facial burn injury (n=105, 64.4%) was significantly higher than previously reported data (33.2%). The result of the study showed that cupping and hotpot were the main causes of alcohol burns in Beijing, which should be taken into consideration for prevention. It is necessary to strengthen safety management of classes at school where experiments are undertaken and to educate the general public on the proper means of disinfecting against COVID-19.


Telestroke in resource-poor developing country model.
Telemedicine is a major effort to tackle the uneven availability of facilities for thrombolysis in acute ischemic stroke. We present a telestroke model introduced in a small hilly state of Himachal Pradesh in India. To provide acute ischemic stroke treatment with tissue plasminogen activator in all district hospitals of Himachal Pradesh with computerized axial tomographic scan facility through Telemedicine. Smartphone-based hub and spoke telestroke model was used with two tertiary care hospitals (with neurologists) as hub and 17 district hospitals (without onsite neurologists) as spokes. The telestroke project was launched in the state of Himachal Pradesh in April 2014. Medical officers in district hospitals (Medicine graduates and Internal Medicine postgraduates) were trained in the treatment of stroke through workshops. Tissue plasminogen activator was made available at all these centers, free of cost through hospital pharmacies. Four neurologists at two tertiary care centers were made available for consultation on phone. Between June 2014 and May 2015, a total of 26 patients received thrombolysis under the telestroke project at nine district hospitals without onsite presence of a neurologist. Eight patients were females and 18 males. The age of patients ranged from 26 to 80 years. Only 2 patients developed an intracranial bleed following thrombolysis, and both were nonfatal. Smartphone-based telestroke services may be a much cheaper alternative to video-conferencing-based telestroke services and are more portable with less technical glitches. To the best of our knowledge, this is the first telestroke model being reported from India. It seems to be the way forward in providing timely treatment in acute ischemic stroke in underserved and resource poor settings.