An oncology pharmacy practice elective course for third-year pharmacy students.
Objective. To develop and implement a 1-credit-hour oncology pharmacy practice elective course for third-year pharmacy students and assess its impact on examination scores in a required pharmacotherapeutics course.Design. Major topics were identified to focus on therapeutic management and supportive care of the oncology patient. Psychosocial topics were incorporated to help pharmacy students better relate to oncology patients.Assessment. Learning was assessed by means of 2 computer-based examinations, weekly reflection posts, and a completed oncology service-learning project and reflection paper. Students enrolled in the course achieved higher pharmacotherapeutics oncology section examination scores than students who had not taken the course. Also, this course increased students' interest in oncology pharmacy.Conclusion. The oncology pharmacy elective course has received overwhelmingly positive feedback from students and student enrollment continues to grow. We will continue to offer this course to future practitioners.


Principles of cryopreservation.
Cryopreservation is the use of very low temperatures to preserve structurally intact living cells and tissues. Unprotected freezing is normally lethal and this chapter seeks to analyze some of the mechanisms involved and to show how cooling can be used to produce stable conditions that preserve life. The biological effects of cooling are dominated by the freezing of water, which results in the concentration of the solutes that are dissolved in the remaining liquid phase. Rival theories of freezing injury have envisaged either that ice crystals pierce or tease apart the cells, destroying them by direct mechanical action, or that damage is from secondary effects via changes in the composition of the liquid phase. Cryoprotectants, simply by increasing the total concentration of all solutes in the system, reduce the amount of ice formed at any given temperature; but to be biologically acceptable they must be able to penetrate into the cells and have low toxicity. Many compounds have such properties, including glycerol, dimethyl sulfoxide, ethanediol, and propanediol. In fact, both damaging mechanisms are important, their relative contributions depending on cell type, cooling rate, and warming rate. A consensus has developed that intracellular freezing is dangerous, whereas extracellular ice is harmless. If the water permeability of the cell membrane is known it is possible to predict the effect of cooling rate on cell survival and the optimum rate will be a trade-off between the risk of intracellular freezing and effects of the concentrated solutes. However, extracellular ice is not always innocuous: densely packed cells are more likely to be damaged by mechanical stresses within the channels where they are sequestered and with complex multicellular systems it is imperative not only to secure cell survival but also to avoid damage to the extracellular structure. Ice can be avoided by vitrification-the production of a glassy state that is defined by the viscosity reaching a sufficiently high value (~10(13) poises) to behave like a solid, but without any crystallization. Toxicity is the major problem in the use of vitrification methods. Whether freezing is permitted (conventional cryopreservation) or prevented (vitrification), the cryoprotectant has to gain access to all parts of the system. However, there are numerous barriers to the free diffusion of solutes (membranes), and these can result in transient, and sometimes equilibrium, changes in compartment volumes and these can be damaging. Hence, the processes of diffusion and osmosis have important effects during the introduction of cryoprotectants, the removal of cryoprotectants, the freezing process, and during thawing. These phenomena are amenable to experiment and analysis, and this has made it possible to develop effective methods for the preservation of a very wide range of cells and some tissues; these methods have found widespread applications in biology and medicine.


Marital status of caregiving daughters and co-residence with dependent parents.
The role of caregiving daughters' marital status is examined as it relates to their sharing households with disabled elderly parents. Married daughters fared best in well-being, income, and social support. Never-married women were the most likely to have never moved out of the parental home. Separated/divorced caregivers, more than the married and widowed, had moved into the parent's home rather than the reverse and widowed daughters had lived in re-formed joint households longest. The main reason for re-forming shared households was disability of the parent. Among other reasons were death or withdrawal of previous caregiver and financial problems, with separated/divorced daughters the most likely to mention finances.


Lung Cancer Screening with Low-Dose CT: What We Have Learned in Two Decades of ITALUNG and What Is Yet to Be Addressed.
The ITALUNG trial started in 2004 and compared lung cancer (LC) and other-causes mortality in 55-69 years-aged smokers and ex-smokers who were randomized to four annual chest low-dose CT (LDCT) or usual care. ITALUNG showed a lower LC and cardiovascular mortality in the screened subjects after 13 years of follow-up, especially in women, and produced many ancillary studies. They included recruitment results of a population-based mimicking approach, development of software for computer-aided diagnosis (CAD) and lung nodules volumetry, LDCT assessment of pulmonary emphysema and coronary artery calcifications (CAC) and their relevance to long-term mortality, results of a smoking-cessation intervention, assessment of the radiations dose associated with screening LDCT, and the results of biomarkers assays. Moreover, ITALUNG data indicated that screen-detected LCs are mostly already present at baseline LDCT, can present as lung cancer associated with cystic airspaces, and can be multiple. However, several issues of LC screening are still unaddressed. They include the annual vs. biennial pace of LDCT, choice between opportunistic or population-based recruitment. and between uni or multi-centre screening, implementation of CAD-assisted reading, containment of false positive and negative LDCT results, incorporation of emphysema. and CAC quantification in models of personalized LC and mortality risk, validation of ultra-LDCT acquisitions, optimization of the smoking-cessation intervention. and prospective validation of the biomarkers.


The polyfactorial model of autism and the question of causality.
After recalling the different pediatric, psychopathological and child psychiatric models of mental disorders in children and adolescents, the author presents in detail the so-called polyfactorial model, which includes primary, secondary, and mixed factors. This model is the epistemological heir of the Freudian concept of "complementary series." The example of autism is then explored as a paradigm of the usefulness of this polyfactorial model. Finally, we reflect on the notion of causality, from Aristotelian causality to epigenetic causality, which could 1 day re-legitimize psychoanalysis and the impact of the relationship on genome expression.


Is the 2015 eye care service delivery profile in Southeast Asia closer to universal eye health need!
The year 2015 status of eye care service profile in Southeast Asia countries was compared with year 2010 data to determine the state of preparedness to achieve the World Health Organization global action plan 2019. Information was collected from the International Agency for Prevention of Blindness country chairs and from the recent PubMed referenced articles. The data included the following: blindness and low vision prevalence, national eye health policy, eye health expenses, presence of international non-governmental organizations, density of eye health personnel, and the cataract surgical rate and coverage. The last two key parameters were compared with year 2010 data. Ten of 11 country chairs shared the information, and 28 PubMed referenced publications were assessed. The prevalence of blindness was lowest in Bhutan and highest in Timor-Leste. Cataract surgical rate was high in India and Sri Lanka. Cataract surgical coverage was high in Thailand and Sri Lanka. Despite increase in number of ophthalmologists in all countries (except Timor-Leste), the ratio of the population was adequate (1:100,000) only in 4 of 10 countries (Bhutan, India, Maldives and Thailand), but this did not benefit much due to unequal urban-rural divide. The midterm assessment suggests that all countries must design the current programs to effectively address both current and emerging causes of blindness. Capacity building and proportionate distribution of human resources for adequate rural reach along with poverty alleviation could be the keys to achieve the universal eye health by 2019.


Latino Community Health Workers: Meeting their Community's Emotional Needs in Intuitively Culturally Appropriate Ways.
Scarcity of trained mental health professionals who speak the language and understand Latino cultures is a significant challenge in Oregon. Latinos, particularly immigrants, present to health settings with a variety of psychosomatic symptoms associated with emotional distress. Generalized fear in an anti-immigrant environment is an exacerbating problem that alienates Latinos, regardless of citizenship or immigration status, preventing them from accessing mental health services. The value of community health workers (CHWs) in addressing the health disparities of marginalized groups is immeasurable, and has the potential to be expanded to also assist in meeting the mental health needs of Latino communities. The role of CHWs in providing help to Latinos who are not served by traditional mental health services is explored. This qualitative, participatory research study, codesigned and delivered by CHWs, reports on the experiences of CHWs working with Latinos in Oregon. Focus groups and a survey were used to gather data from CHWs about their experiences responding to the psychoemotional needs of Latinos. CHWs significantly contribute to meeting the gap in provision of culturally relevant crisis intervention, in the language of Latinos in need. Latinos in Oregon rarely make use of traditional mental health services and/or the services offered are linguistically and culturally inadequate. Health care providers are encouraged to attend to both the mental health and physical needs of Latinos in culturally informed and sensitive ways. Given the shortage of adequately trained mental health providers, CHWs are key in accomplishing these goals.


The Effect of Sedation Protocol on Sedation Level and Pharmacological and Non-Pharmacological Interventions on Mechanically Ventilated Patients.
The use of analgesics and sedatives to provide sedation for Patients in Intensive Care Unit (ICU) is inevitable. The present study aimed to determine the effect of sedation protocol using the Richmond Agitation- Sedation Scale on sedation level and amount of pharmacological and non-pharmacological interventions on patients under mechanical ventilation. This randomized clinical trial was conducted on 79 patients under mechanical ventilation in Zanjan. The patients were recruited using the blocking randomized sampling method. In the experiment group, the sedation was provided hourly, using the Richmond sedation Protocol, during the mechanical ventilation period. The level of sedation and pharmacological and nonpharmacological interventions were compared in the two groups using Fisher exact test. Totally, 40 patients in the experiment and 39 patients in the control groups were evaluated. No significant difference was found between the two groups in terms of confounding variables (age, sex, level of consciousness, Acute Physiologic and Chronic Health Evaluation (APACHE) II criterion, underlying disease, and cause of hospitalization). The level of sedation in the experiment group was significantly closer to the ideal score of the Richmond Scale compared to the control group (p < 0.001). The experimental group received significantly more non-pharmacological interventions and fewer pharmacological interventions compared to the control group (P < 0.001). Using a sedation protocol could provide better sedation levels in patients under mechanical ventilation, and reduce the use of sedative medications, and consequently, the cost of hospitalization. Further research is suggested.


The nervous control of gingival blood flow in cats.
The purpose of the present study was to investigate the nervous control of gingival blood flow in cats. Gingival blood flow was measured by laser Doppler flowmeter in 75 cats during electrical stimulation and cutting or ligation of the inferior alveolar nerve and cervical sympathetic nerve without sympathectomy or pretreatment with adrenoceptor blocking agents. Three different patterns of responses in gingival blood flow were observed following electrical stimulation of the inferior alveolar nerve in cats. In 45 cats there was an increase in blood flow, in 4 cats a decrease in blood flow, and in 7 cats a biphasic change consisting of an initial decrease and a successive increase in blood flow. The vasodilator effect was significantly reduced by pretreatment with (D-Pro2, D-Trp7.9)-substance P. tripelennamine, and methysergide. Pretreatment with cimetidine, atropine, hexamethonium, phentolamine, or propranolol had no effect on vasodilatation. The vasoconstrictor response was completely inhibited by pretreatment with phentolamine; in this case the vasodilator response appeared after stimulation of the inferior alveolar nerve. Ligation or cutting of the inferior alveolar nerve always elicited an increase in gingival blood flow. Cutting the cervical sympathetic nerve had no effect on gingival blood flow in 8 of 10 cats and caused an increase in gingival blood flow in 2 cats; however, electrical stimulation of the cervical sympathetic nerve always caused a decrease in gingival blood flow in the cats investigated. The present results suggest that cat gingival blood flow is controlled by sympathetic alpha-adrenergic fibers for vasoconstriction and by sensory fibers and mast cells for vasodilatation.


Behaviour modification group-treatment of children with recurrent lower urinary tract infections.
It has long been recognized that infrequent micturition and incomplete emptying of the bladder in children represent important factors in the causation of incontinence during the day, and of urinary tract infections (UTI). Behaviour modification is well documented, both as an individual- and a group intervention. The purpose of our study was to develop a programme for group intervention with children, with the aim of improving the children's micturition habits and thereby changing the frequency of wettings, the amount of residual urine, and the UTI frequency. The children responded quickly to the intervention. The amount of residual urine was unaffected, but there are methodological problems in measuring this. There were, however, significant reductions in incontinence and UTI, although there was a tendency to relapse of incontinence over time, probably because of lack of continued follow-up. It is tentatively concluded that the described behavioural intervention seemed effective in improving children's micturition habits, thereby changing the frequency of wettings, and the frequency of urinary tract infections. The treatment seems to be suitable for nursing intervention, either within a hospital setting, or on an outpatient, primary care basis.


Clonal nature of the immune response to phosphorylcholine. I. Specificity, class, and idiotype of phosphorylcholine-binding receptors on lymphoid cells.
The relationship between receptor molecules on antigen-binding lymphocytes (ABC) and antibody produced by antibody-secreting cells was studied in inbred strains of mice using the immune response to phosphorylcholine (PC) as a model system. Splenic and lymph node lymphocytes of nonimmune mice possess rare lymphocytes which bind (125)I-labeled PC-bovine serum albumin. The frequency of PC-ABC increases after immunization and is paralleled by a rise in the frequency of PC-specific antibody-producing cells. Both of these responses are thymus independent. The receptors on these ABC display specificity for PC and are exclusively of the IgM class. In one of the strains, BALB/c, the receptors possess the same idiotype and fine degree of specificity for PC and two of its analogues, glycerophosphorylcholine and choline, that are characteristic of a PC-binding myeloma, HOPC 8. Furthermore, the idiotype and class of the receptor in these mice do not change during the course of the immune response. These data provide more direct evidence for the immunelogic relevance of receptor-bearing lymphocytes.


Low-temperature carbonization and more effective degradation of carbohydrates induced by ferric trichloride.
The present work is devoted to an attempt to understand the effect of an inorganic salt such as ferric trichloride (FeCl(3)) on the carbonization and degradation of carbohydrates such as β-cyclodextrin (CD), amylose, and cellulose. Our data revealed two important observations. First, the presence of FeCl(3) led to the occurrence of a low carbonization temperature of 373 K. This is a rare phenomenon, in which carbonization improvement is present even if a small amount of FeCl(3) was added. Experimental results had provided evidence for the fact that a redox process was started during the low-temperature carbonization of β-CD, causing the reduction of FeCl(3) to ferrous chloride (FeCl(2)) by carbon materials formed in the carbonization process in air. However, the reduction process of FeCl(3) produced the in situ composite nanomaterial of Fe-FeCl(2) combination in nitrogen. Second, a molecule-ion interaction emerged between FeCl(3) and the carbohydrates in aqueous solution, resulting in a more effective degradation of the carbohydrates. Moreover, our results demonstrated that FeCl(3) played the role of a catalyst during the degradation of the carbohydrates in solution. We believe that the current work not only has a significant potential application in disposal of waste carbohydrates but also could be helpful in many fields such as environmental protection, biomass energy development, and inorganic composite nanomaterials.


[Unilateral amaurosis as the only focal symptom caused by dissection of the common carotid artery].
Central retinal artery occlusion with persistent amaurosis as the only focal symptom caused by dissection of the internal carotid artery has occasionally been reported. Central retinal artery occlusion due to a common carotid artery dissection has been diagnosed only very rarely. We describe a patient presenting with cervical pain, headache and unilateral amaurosis due to a thrombosis of the central retinal artery caused by a common carotid artery dissection, as demonstrated on MR imaging. No other neurological deficits could be detected. The patient underwent an anticoagulative treatment without improvement of his vision, but also without the appearance of further neurological symptoms. In monocular visual loss combined with cervical pain or headache, carotid artery dissection should be considered. Early treatment might be of crucial importance for the prevention of a devastating hemispheric stroke.


Emergent macrophytes modify the abundance and community composition of ammonia oxidizers in their rhizosphere sediments.
Ammonia oxidation is a crucial process in global nitrogen cycling, which is catalyzed by the ammonia oxidizers. Emergent plants play important roles in the freshwater ecosystem. Therefore, it is meaningful to investigate the effects of emergent macrophytes on the abundance and community composition of ammonia oxidizers. In the present study, two commonly found emergent macrophytes (Zizania caduciflora and Phragmitas communis) were obtained from freshwater lakes and the abundance and community composition of the ammonia-oxidizing prokaryotes in the rhizosphere sediments of these emergent macrophytes were investigated. The abundance of the bacterial amoA gene was higher in the rhizosphere sediments of the emergent macrophytes than those of bulk sediments. Significant positive correlation was found between the potential nitrification rates (PNRs) and the abundance of bacterial amoA gene, suggesting that ammonia-oxidizing bacteria (AOB) might play an important role in the nitrification process of the rhizosphere sediments of emergent macrophytes. The Nitrosotalea cluster is the dominant ammonia-oxidizing archaea (AOA) group in all the sediment samples. Analysis of AOB group showed that the N. europaeal cluster dominated the rhizosphere sediments of Z. caduciflora and the bulk sediments, whereas the Nitrosospira cluster was the dominant AOB group in the rhizosphere sediments of P. communis.


Computed tomographic study of children with classic autism.
Computed tomographic (CT) scans were obtained for nine autistic boys aged between 9 and 16 years. All were considered to have classic childhood autism of unequivocal diagnosis, with symptoms present from infancy, and were functioning in the borderline or normal level of intelligence. They had performed poorly on tests purported to measure left hemispheric functions. There was no sign of abnormality of any kind on the CT scans or any asymmetry that might be related to lateralized cognitive functions. It is suggested that earlier reported abnormalities are a function of the inclusion of patients with a heterogeneous collection of disorders in the tested sample.


Preparation of Linear Cryogel Arrays as a Microfluidic Platform for Immunochromatographic Assays.
We describe a new microfluidic platform to perform immunochromatographic assays. The platform consists of a linear assembly of small, porous cryogel monoliths functionalized with various biomolecules. The cryogels are anchored in an optically transparent capillary, which serves as the microfluidic carrier. This assembly enables fluid flow by capillary action and simple optical detection. Using an in situ preparation method, individual compartments are generated from small plugs of polymer solutions that are transformed into small individually functionalized cryogel monoliths through a photoinduced cross-linking reaction. In the same reaction step, the monoliths are firmly anchored to the surface of the capillary. As proof-of-concept, a prototype platform is successfully used for the detection of the inflammatory marker interleukin 6 via a sandwich immunoassay. We observe excellent assay performance metrics that include high sensitivity, good linearity, and low variation. We also demonstrate fluid transport solely by passive means, which is a critical attribute for point-of-care diagnostics.


Thermally enhanced Wigner oscillations in two-electron 1D quantum dots.
Motivated by a recent experiment (Pecker et al 2013 Nat. Phys. 9 576), we study the stability, with respect to thermal effects, of Friedel and Wigner density fluctuations for two electrons trapped in a one-dimensional quantum dot. Diagonalizing the system exactly, the finite-temperature average electron density is computed. While the weak and strong interaction regimes display a Friedel oscillation or a Wigner molecule state at zero temperature, which as expected smear and melt as the temperature increases, a peculiar thermal enhancement of Wigner correlations in the intermediate interaction regime is found. We demonstrate that this effect is due to the presence of two different characteristic temperature scales: T(F), dictating the smearing of Friedel oscillations, and T(W), smoothing Wigner oscillations. In the early Wigner molecule regime, for intermediate interactions, T(F) < T(W) leading to the enhancement of the visibility of Wigner oscillations. These results complement those obtained within the Luttinger liquid picture, valid for larger numbers of particles.


Classic Hodgkin lymphoma in young people.
Classic Hodgkin lymphoma (CHL) is a unique form of lymphoid cancer featuring a heterogeneous tumor microenvironment and a relative paucity of malignant Hodgkin and Reed-Sternberg (HRS) cells with characteristic phenotype. Younger individuals (children, adolescents and young adults) are affected as often as the elderly, producing a peculiar bimodal age-incidence profile that has generated immense interest in this disease and its origins. Decades of epidemiological investigations have documented the populations most susceptible and identified multiple risk factors that can be broadly categorized as either biological or environmental in nature. Most risk factors result in overt immunodeficiency or confer more subtle alterations to baseline health, physiology or immune function. Epstein Barr virus, however, is both a risk factor and well-established driver of lymphomagenesis in a significant subset of cases. Epigenetic changes, along with the accumulation of somatic driver mutations and cytogenetic abnormalities are required for the malignant transformation of germinal center-experienced HRS cell precursors. Chromosomal instability and the influence of endogenous mutational processes are critical in this regard, by impacting genes involved in key signaling pathways that promote the survival and proliferation of HRS cells and their escape from immune destruction. Here we review the principal features, known risk factors and lymphomagenic mechanisms relevant to newly diagnosed CHL, with an emphasis on those most applicable to young people.


Oxidation and esterification of cis- and trans-isomers of octadecenoic and octadecadienoic acids in isolated rat liver.
The metabolism of 9-octadecenoic and 9,12-octadecadienoic acids with different geometrical configurations was compared in isolated perfused rat liver. More ketone bodies were produced when the trans-isomers were infused. In contrast, only the cis-isomer augmented the triacylglycerol secretion almost entirely as very-low-density lipoprotein (VLDL). Although these responses were independent of the difference in the degree of unsaturation in both the cis- and trans-isomers, the trans-monoenic acid compared to the trans-dienic acid was incorporated more readily into perfusate and hepatic lipids. Quantitative information was obtained with radioactive tracer experiments. The hepatic uptakes of 9-[10-14C]octadecenoic acids were comparable in the cis- and trans-isomers. The trans-octadecenoic acid compared to the cis counterpart was oxidized more readily and incorporated more into liver phospholipid but less into perfusate and liver triacylglycerol. These reciprocal responses counterbalanced each other. The lower rates of triacylglycerol synthesis and secretion in the liver perfused with the trans-octadecenoic acid was confirmed using [2- 3H]glycerol as a tracer. The marked difference in the channelling of cis- and trans-fatty acids in the pathways of oxidation and esterification seems to modify the VLDL secretion in perfused rat liver. Present observations indicate a considerable difference in the fate of unsaturated fatty acids with different configurations. trans-Fatty acids are expected to be an efficient energy source in animal tissues and may not be hyperlipidemic.


Memory-efficient semantic segmentation of large microscopy images using graph-based neural networks.
We present a graph neural network (GNN)-based framework applied to large-scale microscopy image segmentation tasks. While deep learning models, like convolutional neural networks (CNNs), have become common for automating image segmentation tasks, they are limited by the image size that can fit in the memory of computational hardware. In a GNN framework, large-scale images are converted into graphs using superpixels (regions of pixels with similar color/intensity values), allowing us to input information from the entire image into the model. By converting images with hundreds of millions of pixels to graphs with thousands of nodes, we can segment large images using memory-limited computational resources. We compare the performance of GNN- and CNN-based segmentation in terms of accuracy, training time and required graphics processing unit memory. Based on our experiments with microscopy images of biological cells and cell colonies, GNN-based segmentation used one to three orders-of-magnitude fewer computational resources with only a change in accuracy of $-2\;%$ to $+0.3\;%$. Furthermore, errors due to superpixel generation can be reduced by either using better superpixel generation algorithms or increasing the number of superpixels, thereby allowing for improvement in the GNN framework's accuracy. This trade-off between accuracy and computational cost over CNN models makes the GNN framework attractive for many large-scale microscopy image segmentation tasks in biology.


Urinary tract infections in dogs with spontaneous hypercortisolism - frequency, symptoms and involved pathogens.
Dogs with hypercortisolism are predisposed to developing bacteriuria associated either with clinical signs of cystitis or without clinical signs (subclinical bacteriuria). Based on current guidelines, dogs with subclinical bacteriuria should not be treated with antibiotics because there is no evidence that treatment improves outcome and because unnecessary treatments should be avoided. Before these guidelines were published in 2019, dogs with hypercortisolism and bacteriuria were commonly treated with antibiotics irrespective of clinical signs. Comprehensive data on the frequency of bacterial cystitis, subclinical bacteriuria and the outcome of antimicrobial treatment in dogs with hypercortisolism is sparse. The aims of this study were to investigate dogs with hypercortisolism for the presence of bacterial cystitis and subclinical bacteriuria, to address the pathogens involved, and to assess the outcome of antibiotic treatment. Dogs newly diagnosed with hypercortisolism between 2005 and 2015 from which a urine bacterial culture was available were included. Statistical analysis was performed with non-parametric tests. Of the 161 client-owned dogs included, 29 (18%) showed bacteriuria, which was subclinical in 24 (83%) cases. Escherichia coli was the most commonly isolated pathogen (58%). Bacteriuria was not associated with sex or neutering status. In 14 dogs, follow-up data was available, of which 13 (93%) were treated with antimicrobials for 14 to 28 days. Follow-up bacterial culture (1 to 118 days after cessation of therapy) was negative in 10 (77%) treated dogs; a negative follow-up culture was not associated with gender, age or duration of treatment. Bacteriuria persisted in three treated dogs and the one untreated dog. The prevalence of positive bacterial urinary culture in dogs with hypercortisolism was lower than previously reported. In the majority of dogs, bacteriuria was subclinical. Most dogs had a negative bacterial culture result after antimicrobial treatment; however, more resistant bacteria were detected in persistently positive urine.


Predicting sea levels using ML algorithms in selected locations along coastal Malaysia.
In consideration of the distinct behavior of machine learning (ML) algorithms, six well-defined ML used were carried out in this study for predicting sea level on a day-to-day basis. Data compiled from 1985 to 2018 was utilized for training and testing the developed models. An assessment of the multiple statistics-driven regression algorithms resulted such that each tested location was associated with a particular preferred model. The following were the developed best models for their respective study areas: In Peninsular Malaysia, the interactions linear regression model was the best at Pulau Langkawi (RMSE = 19.066), the Matern 5/2 gaussian process regression model at Geting (RMSE = 49.891), and the trilayered artificial neural network at Pulau Pinang (RMSE = 20.026), while the linear regression model was the best at Sandakan in Sabah, East Malaysia (RMSE = 14.054). Other metrics, such as MAE and R-square, were also at their best values, each providing its best values, further substantiating the RMSE respectively, at each of the study areas. These empirical statistics (or metrics) also revealed that despite employing sea level as the sole parameter, results obtained were exceptional better when utilizing a 7-day lag, regardless of the model used. Notably, lag variables with less than a 7-day lag could degrade the model's accuracy in representing ground reality. The study emphasizes the importance of thorough training and testing of ML to aid decision-makers in developing mitigation actions for the climate change phenomena of sea level rise through reliable ML.


Energy expenditure assessment and validation after acute spinal cord injury.
This study was designed to determine the applicability of the Harris Benedict (HB) equation in predicting energy requirements after acute spinal cord injury (SCI) and to evaluate the accuracy of a 30-minute energy expenditure measurement to determine 24-hour requirements. Prealbumin (PAB) was monitored weekly to assess the patient's response to the nutrition support regimen. Patients with acute isolated SCI requiring mechanical ventilation were studied for 4 weeks postinjury. Predicted energy expenditure was estimated using a modified HB equation (HBEE). The protein goal was 2.0 g/kg or 0.23 g nitrogen/kg admission body weight/day. Nutrition support was initiated within 48 hours if medically feasible. Indirect calorimetry was performed weekly to obtain 24-hour measured total energy expenditure (MTEE) and measured resting energy expenditure (MREE) values. Respiratory quotient, PAB levels, urinary urea nitrogen (UUN), and calculated nitrogen balance were evaluated weekly. Eleven tetraplegic men with a mean age of 32 +/- 8 years were studied. Mean MTEE equaled 95% to 100% HBEE. Mean MREE was not significantly different from the mean MTEE. There was a significant correlation between mean predicted and measured 24-hour energy expenditure for each data point. Mean UUN excretion ranged from 22.3 to 28.5 g/d that resulted in a mean negative nitrogen balance for all 4 weeks. PAB improved significantly over the 4-week study period (p < .001). There was a strong correlation between HBEE and MTEE. A brief REE measurement is adequate to determine daily calorie requirements. Visceral protein synthesis can be achieved despite a negative nitrogen balance.


Changes in the activity of acetylcholinesterase and Na,K-ATPase in human erythrocytes irradiated with X-rays.
The response of human erythrocytes to X-rays in the dose range from 40 Gy to 600 Gy was determined on the basis of changes in the activities of AChE and ATPase. The Na,K-ATPase activity increased above the control value at doses below 200 Gy, while at the doses higher than 200 Gy, it decreased, reaching 96% of the control value at a dose of 600 Gy. In the range of doses up to 200 Gy, the AChE activity, expressed as Vmax, did not change. At higher doses, it fell drastically, reaching 33% of the control value at a dose of 600 Gy. Simultaneously, the enzyme substrate affinity decreased at 200 Gy, and then started to increase at lower values of Vmax. The obtained results suggest that under appropriate conditions, low doses of radiation may have the opposite effects to high doses.


Protein kinase C regulation of terminal deoxynucleotidyl transferase.
Terminal deoxynucleotidyl transferase (TdT) is a nuclear enzyme found in early lymphocytes which is thought to increase junctional diversity of TCR and Ig genes by the addition of N regions. TdT is normally found only in immature lymphoid cells and is turned off in both mature B and T cells. To investigate the regulation of TdT gene expression, pre-B and pre-T cells were treated with PMA or three of its analogs and its effects on steady-state TdT mRNA levels determined. Rapid and reversible decline in steady-state TdT mRNA levels was observed within 6 h with PMA. This rapid decline can be blocked by pretreatment of the cells with a relatively selective protein kinase C inhibitor implicating the role of protein kinase C activation in the decline of TdT mRNA. Nuclear run-off studies demonstrate that TdT transcription is rapidly down-regulated within 45 min after PMA treatment, indicating that this regulation occurs mainly at the level of transcription. Furthermore, the TdT mRNA decline is blocked in the presence of cycloheximide, showing that new protein synthesis is required for inactivation of the gene.


Oligomycin A enhances apoptotic effect of TRAIL through CHOP-mediated death receptor 5 expression.
Development of resistance to TNF-related apoptosis-inducing ligand (TRAIL) in tumor cells is one of the important problems in cancer treatment. Despite the previous report demonstrating that oligomycin suppressed TNF-induced apoptosis, in our screening of small molecules enhancing cancer cell death to TRAIL, oligomycin A (OMA) was found to enhance TRAIL-induced apoptosis in HeLa cells. CCAAT/enhancer-binding protein homologous protein (CHOP) was found to directly bind to death receptor 5 (DR5) promoter through endoplasmic reticulum stress (ER-stress) signaling and sensitize the cells to TRAIL. Among ER-stress associated proteins, OMA triggered the inositol-requiring enzyme 1 (IRE1) signaling pathway, leading to X-binding protein 1 (XBP1) splicing, CHOP expression and DR5 upregulation. In contrast, small-interfering RNA (siRNA) of CHOP reduced the number of apoptotic cells in response to the co-treatment of TRAIL and OMA. Collectively, our data suggest that OMA enhances apoptotic death of cervical cancer cells to TRAIL through upregulation of CHOP-mediated DR5 expression following ER-stress.


Common and Unique Factors and the Bidirectional Relationship Between Chronic Kidney Disease and Nonalcoholic Fatty Liver in Type 2 Diabetes Patients.
This study aimed to investigate the common and unique risk factors and bidirectional relationship between chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). This was a cross-sectional study of patients with T2DM enrolled in a disease management program at two specialized diabetes outpatient clinics. Common and unique risk factors for CKD and NAFLD were examined using structural equation models (SEMs). SEMs were also used to examine direct and indirect effects of NAFLD on CKD and those of CKD on NAFLD. A total of 1992 subjects with T2DM were enrolled in this study. In multivariate analysis, NAFLD was independently associated with the odds of CKD (adjusted odds ratio=1.59, 95% confidence interval=1.12-2.25, P=0.009). SEMs showed that age, triglyceride, uric acid (UA), albumin, and HbA1c levels had statistically significant direct effects on CKD, and the final model could explain 22% of the variability in CKD. Age, triglycerides, body mass index (BMI), UA, white blood cell (WBC) count, serum glutamic pyruvic transaminase (SGPT) level, and smoking status had statistically significant direct effects on NAFLD, and the final model could explain 43% of the variability in NAFLD. The common risk factors contributing to both CKD and NAFLD were age, triglycerides, and UA. The unique risk factors were albumin and HbA1c for CKD, and BMI, WBC, SGPT, and smoking for NAFLD. In addition, SEM analysis also confirmed the bidirectional causal relationship between NAFLD and CKD. Common and unique risk factors and a bidirectional relationship existed between CKD and NAFLD in our patients with T2DM.


Corticotropin regulates vascular endothelial growth factor expression in human fetal adrenal cortical cells.
The human adrenal cortex has a complex vasculature that is essential for growth, organ maintenance, and access of secreted hormones to the circulation. Growth and function of the adrenal cortex are regulated by corticotropin (ACTH), the actions of which are in part mediated by locally produced growth factors. As cortical growth and vascularization must increase in a coordinated manner, we hypothesized that ACTH also influences adrenal cortical angiogenesis by stimulating the local expression of specific angiogenic factors. Vascular endothelial growth factor (VEGF) is a potent endothelial cell-specific angiogenic peptide, the expression of which has been detected in adrenal cortical cells. Therefore, we examined the localization of VEGF expression in the midgestation (16-20 weeks) human fetal adrenal cortex and determined whether VEGF expression and secretion by isolated human fetal adrenal cortical cells are regulated by ACTH. By immunohistochemical analysis, strong cytoplasmic staining for VEGF was detected in scattered clusters of fetal zone (inner cortical compartment) cells. In contrast, cells in the outer, definitive zone of the cortex stained only weakly for VEGF. The predominant staining for VEGF in the fetal zone correlated with the extensive vasculature of this zone as detected by immunohistochemical staining for von Willebrand factor, which is specific for endothelial cells. In primary cultures of human fetal adrenal cortical cells, ACTH (1 nmol/L) and forskolin (10 micromol/L) increased the abundance of messenger ribonucleic acid transcripts encoding VEGF, as assessed by Northern and slot blot analyses. The stimulatory effect of ACTH and forskolin on VEGF gene expression occurred within 2 h of agonist exposure and persisted for at least 24 h. ACTH and forskolin also increased VEGF protein secretion by fetal adrenal cortical cells, as assessed by enzyme-linked immunosorbent assay for VEGF in fetal adrenal cortical cell-conditioned medium. A significant (P < 0.05) increase in VEGF secretion was detected as early as 8 h after ACTH or forskolin treatment. By 24 h after the addition of ACTH or forskolin, VEGF secreted from isolated human fetal adrenal cells was increased 5- to 6-fold. These data demonstrate that the human fetal adrenal cortex, particularly the cells of the inner fetal zone, express VEGF and that VEGF expression and secretion by these cells are directly regulated by ACTH and the activation of adenylate cyclase. Thus, VEGF may be a local regulator of adrenal cortical angiogenesis and an important mediator of the tropic action of ACTH, ensuring the coordination of ACTH-stimulated cortical growth and vascularization.


On the Stiles-Crawford effect with age.
To determine whether the Stiles-Crawford effect remains stable after subjects have aged 30 years. The relative luminous efficiency as a function of pupil position (Stiles-Crawford effect) was determined for the same seven subjects on the same apparatus in the 1960s and in 1995. The pupil opening was traversed nine times, at 20 degrees azimuth intervals. Data were fit with a revolution paraboloid yielding a peak position (x0, y0) and a peakedness (rho). Two of seven subjects showed a significant, but small, decrease in rho, and the other five showed, no change. No clear outcome in x0, y0 changes could be reported because of differences in pupil dilation then and now. Although exceptions are found on the stability of the Stiles-Crawford effect with age, the authors can still conclude that it is stable.


Localization of the CyanoP binding site on photosystem II by surface plasmon resonance spectroscopy.
Photosystem II (PSII), a large multi subunit membrane protein complex localized in the thylakoid membrane of cyanobacteria and chloroplasts, is the only known enzyme that catalyzes the light-driven oxidation of water. In addition to the membrane intrinsic part of PSII, efficient oxygen evolution requires soluble protein subunits at its luminal interface. In contrast to the detailed crystal structure of the active cyanobacterial complex the characterization of intermediate PSII species related to its assembly and repair is hampered by their instability or low abundance. As most structural variations of the corresponding PSII species are based on a different set of protein factors bound to the luminal interface of the complex we developed a system for interaction analysis between PSII and its soluble interaction partners based on surface plasmon resonance (SPR) spectroscopy. The assay was validated by the correct localization of the extrinsic PSII proteins PsbO, PsbV, and PsbU on the luminal PSII surface and used to determine the unknown binding position of CyanoP, the cyanobacterial homolog of higher plant PsbP. The CyanoP binding site was clearly localized in the center of PSII at a position, which is occupied by the PsbO subunit in mature PSII complexes. Consistently, we demonstrate selective binding of CyanoP to an inactive PSII assembly intermediate that lacks the extrinsic subunits PsbO, PsbV, and PsbU. These findings suggest, that CyanoP functions in the dynamic lifecycle of PSII, possibly in the association of CP47 and CP43 or in photoactivation of the oxygen-evolving complex.


Effect of the W mutation, for white belly spot, on testicular germ cell differentiation in mice.
The effect of the mutation for white belly spot controlled by the dominant gene W on spermatogenesis in mice was examined by experimental cryptorchidism and its surgical reversal. The course of spermatogenesis from spermatogonia to spermatid was normal in intact testes of W/+ mice. In cryptorchid testes, there was no difference in the number and activity of Type A spermatogonia between the testes of W/+ and +/+ mice, in mitotic and labelling indices. Although surgical reversal of the cryptorchid testis resulted in regenerative differentiation of germ cells in both genotypes, the recovery of cell differentiation in the W/+ testis was slower than in the +/+ testis. There were fewer germ cells, such as intermediate-Type B spermatogonia or more advanced ones, in W/+ testes. On Day 17 after surgical reversal, cell associations in W/+ testes were abnormal and the numbers of intermediate-Type B spermatogonia, spermatocytes and spermatids were approximately 70, 50 and 15%, respectively, of those in +/+ testes. These results indicate that the W gene affects spermatogenic cell differentiation in adult mice.


Anxiety provoking situations in Indian families.
Life situations pertaining to the relationship dimension are viewed in respect of families of anxiety patients and normals. Grand-parents' interference, parents-in-law relationships, parents' role functioning, siblings' interaction, marital relationships and other relatives' cooperation are studied for 20 anxiety patients and 40 normals based on group matching. It was found that frequent interference of grand-parents, dissatisfaction with parents-in-law, inadequate mutually contradictory parents' role functioning, disharmonious siblings interaction, threatening and conflicting marital life and lack of cooperation and support on the part of other relatives seem to be sources of anxiety in the Indian setting.


Design and Synthesis of Triazole-Containing HDAC Inhibitors That Induce Antitumor Effects and Immune Response.
Histone deacetylase (HDAC) is an epigenetic antitumor drug target, but most existing HDAC inhibitors show limited antitumor activity and their use is often accompanied by serious adverse effects. To overcome these problems, we designed and synthesized a series of triazole-containing compounds as novel HDAC inhibitors. Among them, compound 19h exhibited potent and selective inhibition of HDAC1, with good antiproliferative activity in vitro and an excellent pharmacokinetic profile. Compound 19h significantly inhibited the growth of human tumor xenografts in nude mice and murine tumor growth in immune-competent mice bearing MC38 colon cancer. In the MC38 model, 19h increased the ratio of splenic CD4+ T effector cells and promoted complete tumor regression in 5/6 animals when combined with the mPD-1 antibody. These results suggested that selective class I HDAC inhibitors exert direct tumor growth inhibition and indirect immune cell-mediated antitumor effects and are synergistic with immune checkpoint inhibitors.


Synthetic analogues of the proteinase inhibitor: chymostatin.
Putative proteinase inhibitors with the general structure Z. Arg. X.Phe.H (where X = Leu, Ile or Val) were prepared by solution synthesis using semicarbazone protection for the aldehyde function. These inhibitors showed strong activity towards chymotrypsin whereas the semicarbazones and dipeptides aldehydes showed considerably reduced activity. The structural requirements for inhibition would seem to mimic those of the natural chymotrypsin inhibitor chymostatin.


A New Technique for Conchal Cartilage Harvest.
The goal of auricular cartilage harvest is to obtain a sufficient amount for reconstruction and to minimize the change in ear shape. The cartilage can be harvested by a posterior or anterior approach, and each method has advantages and disadvantages. The posterior approach presents the advantage of scar concealment, but there are limits to the amount of cymba cartilage that may be harvested. In contrast, the anterior approach may cause a noticeable scar. However, as cartilage is collected, the anterior approach provides a view that facilitates the preservation ear structure. In addition, it is possible to obtain a greater amount of cartilage. From January 2014 to December 2015, we harvested auricular cartilage graft material in 17 patients. To prevent the development of trapdoor scars or linear scar contracture, short incisions were made on the superior border of the cymba and cavum. Two small and narrow incisions were made, resulting in suboptimal exposure of the surgical site, which heightens the potential for damaging the cartilage when using existing tools. To minimize this, the authors used a newly invented ball-type elevator. All patients recovered without complications after surgery and reported satisfaction with the shape of the ear.


Expression of cry3A gene and its toxicity against Asian Gray Weevil Myllocerus undecimpustulatus undatus Marshall (Coleoptera: Curculionidae).
Coleopterans are the most damaging pests of many agricultural and forestry crops; there is an urgent need to develop effective biopesticides against these insects. Enhancers of Bt toxicity typify an opportunity to improve currently available commercial products into more effective control agents against diverse pests. A 1.9 kb DNA fragment, PCR amplified from native isolates of Bt using cry3A gene specific primers was cloned in expression vector pQE-80L and then used for transformation of Escherichia coli M15 cells. The sequence of the cloned crystal protein gene showed almost complete homology with a Coleopteran active Cry3A toxin gene with 117 mutations scattered in different domain regions encoding a protein of 645 amino acid residues in length, with a predicted molecular mass of 77.4 kDa. Phylogenetic analysis could be compulsive for new/novel Bacillus thuringiensis strains, allowing them to be grouped with related Cry proteins. The toxicity of Bt protein was determined against Myllocerus undecimpustulatus undatus Marshall (Coleoptera: Curculionidae) LC50 152 ng cm(-2). Genes coding for Coleopteran active Cry3A proteins have been isolated and their efficient expression will provide the tools necessary to increase the efficacy of Cry-based biopesticide against economically important beetles.


Severely Affected by Parkinson Disease: The Patient's View and Implications for Palliative Care.
People severely affected by Parkinson disease (PD)/atypical parkinsonism (AP) comprise a heterogeneous group with distinct needs, which so far remain largely unexamined. The aim of our study was to analyze reasons for feeling severely affected and document unmet needs in a patient subgroup severely affected by PD/AP using solely a subjective inclusion criterion. Patients feeling severely affected by PD/AP were recruited via a magazine published by the German Parkinson Association. A questionnaire was sent out nationwide. Besides analyzing the closed-ended questions, a subsample of 40% was analyzed regarding the open-ended questions using content analysis. Correlations between subjectively felt severe affectedness and objective criteria were calculated. Eight hundred fourteen questionnaires were analyzed. Sample characteristics were: mean age 70 years; 60.3% male; time since diagnosis up to 37 years; and Hoehn and Yahr score (if known) 3 (44.6%), followed by 4 (23.9%). Significant associations were observed between subjectively felt severe affectedness and Hoehn and Yahr ( P ≤ .05), poorer health ( P ≤ .01), higher nursing care level ( P ≤ 0.01), and having no children ( P ≤ .05). Most common reasons for feeling severely affected were mobility impairment (34.9%), coordination problems (17.0%), speech problems (12.2%), and limited day-to-day activities (7.8%). Most often expressed unmet needs were support in everyday life (28.1%), medical treatment (15.2%), help with financial services (11.6%), and social integration (9.9%). To meet the complex needs, an integrated multidisciplinary and multiprofessional approach is indicated befitting palliative care principles. Herein, home-based services seem of special importance for patients in advanced disease stages.


Factors associated with stigma and manifestations experienced by Indian health care workers involved in COVID-19 management in India: A qualitative study.
Healthcare personnel who deal with COVID-19 experience stigma. There is a lack of national-level representative qualitative data to study COVID-19-related stigma among healthcare workers in India. The present study explores factors associated with stigma and manifestations experienced by Indian healthcare workers involved in COVID-19 management. We conducted in-depth interviews across 10 centres in India, which were analysed using NVivo software version 12. Thematic and sentiment analysis was performed to gain deep insights into the complex phenomenon by categorising the qualitative data into meaningful and related categories. Healthcare workers (HCW) usually addressed the stigma they encountered when doing their COVID duties under the superordinate theme of stigma. Among them, 77.42% said they had been stigmatised in some way. Analyses revealed seven interrelated themes surrounding stigma among healthcare workers. It can be seen that the majority of the stigma and coping sentiments fall into the mixed category, followed by the negative sentiment category. This study contributes to our understanding of stigma and discrimination in low- and middle-income settings. Our data show that the emergence of fear of the virus has quickly turned into a stigma against healthcare workers.


Experimental studies on complete global brain ischemia using the isohistogenic infantile head transplant model in Lewis rats.
A new experimental model is presented, using isohistogenic Lewis rats and microsurgical techniques. Transplantation of the head and forelimbs of the infantile rat was done to the groin of an adult rat. The goal was to study the effects of ischemia on brain tissue. This model also proved useful for other experiments in studies of facial and cranial bone growth. The model presented proved efficient for the study goals, and long-term experiments were possible. The maximum ischemia time tolerated by brain tissue was found to be somewhere between 60 min and 120 min.


Elevated Slit2 Activity Impairs VEGF-Induced Angiogenesis and Tumor Neovascularization in EphA2-Deficient Endothelium.
Angiogenic remodeling during embryonic development and in adult tissue homeostasis is orchestrated by cooperative signaling between several distinct molecular pathways, which are often exploited by tumors. Indeed, tumors upregulate proangiogenic molecules while simultaneously suppressing angiostatic pathways to recruit blood vessels for growth, survival, and metastatic spread. Understanding how cancers exploit proangiogenic and antiangiogenic signals is a key step in developing new, molecularly targeted antiangiogenic therapies. While EphA2, a receptor tyrosine kinase (RTK), is required for VEGF-induced angiogenesis, the mechanism through which these pathways intersect remains unclear. Slit2 expression is elevated in EphA2-deficient endothelium, and here it is reported that inhibiting Slit activity rescues VEGF-induced angiogenesis in cell culture and in vivo, as well as VEGF-dependent tumor angiogenesis, in EphA2-deficient endothelial cells and animals. Moreover, blocking Slit activity or Slit2 expression in EphA2-deficient endothelial cells restores VEGF-induced activation of Src and Rac, both of which are required for VEGF-mediated angiogenesis. These data suggest that EphA2 suppression of Slit2 expression and Slit angiostatic activity enables VEGF-induced angiogenesis in vitro and in vivo, providing a plausible mechanism for impaired endothelial responses to VEGF in the absence of EphA2 function. Modulation of angiostatic factor Slit2 by EphA2 receptor regulates endothelial responses to VEGF-mediated angiogenesis and tumor neovascularization.


Automated Reconstruction of Neural Trees Using Front Re-initialization.
This paper proposes a greedy algorithm for automated reconstruction of neural arbors from light microscopy stacks of images. The algorithm is based on the minimum cost path method. While the minimum cost path, obtained using the Fast Marching Method, results in a trace with the least cumulative cost between the start and the end points, it is not sufficient for the reconstruction of neural trees. This is because sections of the minimum cost path can erroneously travel through the image background with undetectable detriment to the cumulative cost. To circumvent this problem we propose an algorithm that grows a neural tree from a specified root by iteratively re-initializing the Fast Marching fronts. The speed image used in the Fast Marching Method is generated by computing the average outward flux of the gradient vector flow field. Each iteration of the algorithm produces a candidate extension by allowing the front to travel a specified distance and then tracking from the farthest point of the front back to the tree. Robust likelihood ratio test is used to evaluate the quality of the candidate extension by comparing voxel intensities along the extension to those in the foreground and the background. The qualified extensions are appended to the current tree, the front is re-initialized, and Fast Marching is continued until the stopping criterion is met. To evaluate the performance of the algorithm we reconstructed 6 stacks of two-photon microscopy images and compared the results to the ground truth reconstructions by using the DIADEM metric. The average comparison score was 0.82 out of 1.0, which is on par with the performance achieved by expert manual tracers.


Gravitational sliding of the Mt. Etna massif along a sloping basement.
Geological field evidence and laboratory modelling indicate that volcanoes constructed on slopes slide downhill. If this happens on an active volcano, then the movement will distort deformation data and thus potentially compromise interpretation. Our recent GPS measurements demonstrate that the entire edifice of Mt. Etna is sliding to the ESE, the overall direction of slope of its complex, rough sedimentary basement. We report methods of discriminating the sliding vector from other deformation processes and of measuring its velocity, which averaged 14 mm year-1 during four intervals between 2001 and 2012. Though sliding of one sector of a volcano due to flank instability is widespread and well-known, this is the first time basement sliding of an entire active volcano has been directly observed. This is important because the geological record shows that such sliding volcanoes are prone to devastating sector collapse on the downslope side, and whole volcano migration should be taken into account when assessing future collapse hazard. It is also important in eruption forecasting, as the sliding vector needs to be allowed for when interpreting deformation events that take place above the sliding basement within the superstructure of the active volcano, as might occur with dyke intrusion or inflation/deflation episodes.


Intraoperative somatosensory evoked potential recovery following opening of the fourth ventricle during posterior fossa decompression in Chiari malformation: case report.
The most appropriate surgical technique for posterior fossa decompression in Chiari malformation (CM) remains a matter of debate. Intraoperative electrophysiological studies during posterior fossa decompression of Type I CM (CM-I) aim to shed light on the entity's pathomechanism as well as on the ideal extent of decompression. The existing reports on this issue state that significant improvement in conduction occurs after craniotomy in all cases, but additional durotomy contributes a further improvement in only a minority of cases. This implies that craniotomy alone might suffice for clinical improvement without the need of duraplasty or even subarachnoid manipulation at the level of the craniocervical junction. In contrast to published data, the authors describe the case of a 32-year-old woman who underwent surgery for CM associated with extensive cervicothoracic syringomyelia and whose intraoperative somatosensory evoked potentials (SSEPs) did not notably improve after craniotomy or following durotomy; rather, they only improved after opening of the fourth ventricle and restoration of CSF flow through the foramen of Magendie. Postoperatively, the patient recovered completely from her preoperative neurological deficits. To the authors' knowledge, this is the first report of significant SSEP recovery after opening the fourth ventricle in the decompression of a CM-I. The electrophysiological and operative techniques are described in detail and the findings are discussed in the light of available literature. The authors conclude that there might be a subset of CM-I patients who require subarachnoid dissection at the level of the craniocervical junction to benefit clinically. Prospective studies with detailed electrophysiological analyses seem warranted to answer the question regarding the best surgical approach in CM-I decompression.


An Unusual False-Positive Uptake of Radioiodine Caused by Breast Implants.
A 40-year-old woman with a history of papillary thyroid cancer underwent ablative 131I therapy. Postablation whole-body 131I scintigraphy revealed not only increased activity in the thyroid bed but also in the anterior part of the chest. SPECT/CT images localized the activity in the bilateral breast implants.


Cytotoxic activity of diterpenoids isolated from the aerial parts of Elaeoselinum asclepium subsp. meoides.
The phytochemical investigation of the acetone extract of the aerial parts of Elaeoselinum asclepium (L.) Bertol. subsp. meoides (Desf.) Fiori afforded several known diterpenoids as well as meoidic acid ( 5), new in the literature. The cytotoxic activities of elasclepic acid ( 1), ENT-atis-16-en-19-oic acid ( 2), ent-beyer-15-en-19-oic acid ( 3), ent-kaur-16-en-19-oic acid ( 4) and meoidic acid ( 5) were investigated on rat glioma C6 cells by evaluation of cell growth inhibition.


A nurse-led service for termination of pregnancy.
The development of a procedure for a medical termination of pregnancy offers patients greater choice. Nurse-led units aim to provide a supportive, holistic service to patients. Patients value being given detailed written and verbal information and being supported in a dedicated unit.


Distal deep venous thrombosis in a hemophilia A patient with inhibitor and severe infectious disease, 18 days after recombinant activated factor VII transfusion.
We describe a 38 year old hemophilia A patient with a factor VIII inhibitor who was admitted to our Hematology Department in January 2001 with a seriously infected and bleeding perianal ulcer. To treat infection and bleeding the patient received broad spectrum antibiotics and recombinant activated factor VII (rFVIIa) (Novoseven(R)) for about 1 month (see detailed time of administration and dosing schedule of rFVIIa further in text). Eighteen days after his last rVIIa infusion the patient developed an ultrasound proven right calf vein thrombosis. In the whole period of admission, preceding the thrombotic event the patient biologically showed a picture of severe systemic inflammatory disease as indicated by persistent increased levels of D-dimer and fibrinogen (table). It is an interesting point of discussion whether the calf thrombosis was provoked as a consequence of rFVIIa infusion (with symptoms 18 days after the last infusion) or as a consequence of long-standing immobilization and severe inflammatory disease immobilization and severe infection are conditions well known for promoting venous thromboembolic disease.


Quantitative magnetic resonance morphometry of extraocular muscles: a new diagnostic tool in paralytic strabismus.
Paralytic strabismus is often diagnostically ambiguous due to the similarity of patterns of misalignment produced by different mechanisms. To address this problem, we have developed a new technique employing high-resolution, surface coil magnetic resonance imaging to quantify extraocular muscle size and contractility. Adjacent coronal images are obtained spanning the anteroposterior extent of each orbit, and repeated in multiple directions of gaze. Contractility is evaluated from analysis of muscle cross-sectional areas. The quantitative size and contractile characteristics of normal rectus and superior oblique muscles are reviewed, along with the effects of superior oblique palsy. The morphometric features of lateral rectus palsy are illustrated by three clinical cases exhibiting deficient contractility and atrophy of the lateral rectus muscle. A case of superior oblique palsy is presented illustrating atrophy and lack of contractility of the involved superior oblique muscle. This imaging technique can be employed in any clinical center and permits insight into extraocular muscle function in complex strabismus cases.


Comprehensive discovery of subsample gene expression components by information explanation: therapeutic implications in cancer.
De novo inference of clinically relevant gene function relationships from tumor RNA-seq remains a challenging task. Current methods typically either partition patient samples into a few subtypes or rely upon analysis of pairwise gene correlations that will miss some groups in noisy data. Leveraging higher dimensional information can be expected to increase the power to discern targetable pathways, but this is commonly thought to be an intractable computational problem. In this work we adapt a recently developed machine learning algorithm for sensitive detection of complex gene relationships. The algorithm, CorEx, efficiently optimizes over multivariate mutual information and can be iteratively applied to generate a hierarchy of relatively independent latent factors. The learned latent factors are used to stratify patients for survival analysis with respect to both single factors and combinations. These analyses are performed and interpreted in the context of biological function annotations and protein network interactions that might be utilized to match patients to multiple therapies. Analysis of ovarian tumor RNA-seq samples demonstrates the algorithm's power to infer well over one hundred biologically interpretable gene cohorts, several times more than standard methods such as hierarchical clustering and k-means. The CorEx factor hierarchy is also informative, with related but distinct gene clusters grouped by upper nodes. Some latent factors correlate with patient survival, including one for a pathway connected with the epithelial-mesenchymal transition in breast cancer that is regulated by a microRNA that modulates epigenetics. Further, combinations of factors lead to a synergistic survival advantage in some cases. In contrast to studies that attempt to partition patients into a small number of subtypes (typically 4 or fewer) for treatment purposes, our approach utilizes subgroup information for combinatoric transcriptional phenotyping. Considering only the 66 gene expression groups that are found to both have significant Gene Ontology enrichment and are small enough to indicate specific drug targets implies a computational phenotype for ovarian cancer that allows for 366 possible patient profiles, enabling truly personalized treatment. The findings here demonstrate a new technique that sheds light on the complexity of gene expression dependencies in tumors and could eventually enable the use of patient RNA-seq profiles for selection of personalized and effective cancer treatments.


Scrub Typhus Complicated With Fulminant Perimyocarditis.
A 62-year-old woman with no systemic disease presented to the emergency department (ED) with acute febrile illness for three days. During her ED course, she developed respiratory distress and refractory cardiogenic shock with ST-elevation on electrocardiography. No occluded coronary vessel was found in angiography, and perimyocarditis was impressed. The serum indirect immunofluorescence assay was positive for scrub typhus. Hemopericardium and subsequently intracranial hemorrhage occurred on the 4th hospital day even under intensive care, and the patient expired. Perimyocarditis is a rare but fatal complication of scrub typhus. Through this case report, we aim to convey the genuine possibility that a fulminant perimyocarditis may occur in a previously healthy adult as a potential complication of scrub typhus. By recognizing the risk factors of scrub typhus-related myocarditis, an ED physician can maintain a high index of suspicion for the cardiac complication and intervene in a timely manner.


[Autonomic nervous function in patients with vertigo--evaluation for static function, variation and dynamic change using power spectral analysis of RR intervals].
Power spectral analysis of RR intervals (PSA) of 94 vertiginous patients with associated autonomic nervous dysfunction (AND group), 31 patients with vertebro-basilar insufficiency (VBI group) and 25 controls were analyzed in supine and upright positions. In addition static function, variation from the supine to the upright position and dynamic change in autonomic nervous function (ANF) from the supine to the upright position were examined. Heart rate was recorded for 120 seconds in the supine and 40 seconds in the upright position. RR intervals for each 20-second period were computed using FFT (Fast Fourier Transformation), and the ratio of low frequency power (0.05-0.15 Hz) to high frequency power (0.15-0.4 Hz) (L/H) of PSA were analyzed as an index of sympathetic activity. The PSA was examined by the following three parameters; L/H at rest during the 80-second period from 20 to 100 seconds (static function), the L/H variation between each 20-second period from 0 to 160 seconds (variation) and the ratio of L/H to that in the upright position (dynamic change). The results of PSA were compared with those of pulse wave velocity (PWV) and the coefficient of variation of the RR interval (CVRR), and association between attacks of vertigo and ANF was determined. The results of static function of PSA and the results of PWV and CVRR were very similar, indicating that both methods are useful for evaluating ANF in vertiginous patients. In the AND group the variation in sympathetic activity tended to be larger in patients with sympathetic hyperfunction and parasympathetic hypofunction and in the patients with sympathetic hypofunction and parasympathetic hyperfunction resulting from PWV and CVRR, than in the controls. The dynamic change in patients with sympathetic hyperfunction and parasympathetic hypofunction resulting from PWV and CVRR was also significantly lower than that in the controls (p < 0.01). Some patients in the AND group already showed excessive sympathetic hyperfunction at rest, and changing the position from supine to upright might trigger sympathetic hypofunction, causing an attack of vertigo. The PSA results in the VBI group were similar to those in the controls, suggesting that sympathetic dysfunction did not affect VBI induced vertigo.


[Surgical diseases of the adrenal glands in childhood--pediatric aspects].
Detailed discussion of diseases of the adrenals in children where surgery may be indicated, seen from the paediatric point of view. Following differentiation between adrenal insufficiency and adrenal hyperfunction, as well as adrenal haemorrhage--where differential diagnosis is often rather difficult--the tumours of the zona glomerulosa, fasciculata and reticularis as well as of the adrenal medulla are presented and their signs and symptoms, their clinical hormonal diagnosis, localisation diagnosis and therapy are described.


Matching the Statistical Model to the Research Question for Dental Caries Indices with Many Zero Counts.
Marginalized zero-inflated count regression models have recently been introduced for the statistical analysis of dental caries indices and other zero-inflated count data as alternatives to traditional zero-inflated and hurdle models. Unlike the standard approaches, the marginalized models directly estimate overall exposure or treatment effects by relating covariates to the marginal mean count. This article discusses model interpretation and model class choice according to the research question being addressed in caries research. Two data sets, one consisting of fictional dmft counts in 2 groups and the other on DMFS among schoolchildren from a randomized clinical trial comparing 3 toothpaste formulations to prevent incident dental caries, are analyzed with negative binomial hurdle, zero-inflated negative binomial, and marginalized zero-inflated negative binomial models. In the first example, estimates of treatment effects vary according to the type of incidence rate ratio (IRR) estimated by the model. Estimates of IRRs in the analysis of the randomized clinical trial were similar despite their distinctive interpretations. The choice of statistical model class should match the study's purpose, while accounting for the broad decline in children's caries experience, such that dmft and DMFS indices more frequently generate zero counts. Marginalized (marginal mean) models for zero-inflated count data should be considered for direct assessment of exposure effects on the marginal mean dental caries count in the presence of high frequencies of zero counts.


Sensitivity of bacteria to diamond nanoparticles of various size differs in gram-positive and gram-negative cells.
In this study, the influence of the size and surface termination of diamond nanoparticles (DNPs) on their antibacterial activity against Escherichia coli and Bacillus subtilis was assessed. The average size and distribution of DNPs were determined by dynamic light scattering and X-ray diffraction techniques. The chemical composition of the DNPs studied by X-ray photoelectron spectroscopy showed that DNPs > 5 nm and oxidized particles have a higher oxygen content. The antibacterial potential of DNPs was assessed by the viable count method. In general, E. coli exhibited a higher sensitivity to DNPs than B. subtilis. However, in the presence of all the DNPs tested, the B. subtilis colonies exhibited altered size and morphology. Antibacterial activity was influenced not only by DNP concentration but also by DNP size and form. Whereas untreated 5-nm DNPs were the most effective against E. coli, the antibacterial activity of 18-50-nm DNPs was higher against B. subtilis. Transmission electron microscopy showed that DNPs interact with the bacterial surface, probably affecting vital cell functions. We propose that DNPs interfere with the permeability of the bacterial cell wall and/or membrane and hinder B. subtilis colony spreading.


A method for urine collection in infants.
A simple, inexpensive, non-invasive method for urine collection was used in 28 consecutive infants for periods of 48 hours (n = 10) and 72 hours (n = 18). The incidence of urine collector detachment was low on the first and second days (< 4%) and increased significantly on the third day (28%). Volume of urine leaked was < 4% of the total volume collected daily. This method is applicable to both sexes and is reliable for up to 48 hours.


Long-Term Comparative Outcomes of Patients With Peripheral Artery Disease With and Without Concomitant Coronary Artery Disease.
There are limited contemporary data on guideline-directed medical therapy (GDMT) utilization and long-term clinical outcomes in patients with peripheral artery disease (PAD) with and without concomitant coronary artery disease (CAD). From 2006 to 2013, 879 patients with claudication or critical limb ischemia (CLI) underwent diagnostic angiography or therapeutic endovascular intervention at our multidisciplinary vascular center. GDMT use was assessed at the time of angiography, and major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality were determined during 5 years of follow-up. Cox proportional hazard modeling was used to adjust for baseline differences between patients with and without concomitant CAD. Despite a higher adherence to GDMT (all p ≤0.002) for the use of aspirin, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and statins, patients with PAD and concomitant CAD had higher unadjusted 5-year rates of MACCE (hazard ratio [HR] 1.7, 95% CI 1.3 to 2.1, p = 0.0001) and all-cause mortality (HR 1.86, 95% CI 1.4 to 2.4, p = 0.0001). After adjustment for baseline co-morbidities, the presence of CAD remained an independent risk factor for mortality (adjusted HR 1.35, 95% CI 1.02 to 1.80, p = 0.04) but not for MACCE (adjusted HR 1.24, 95% CI 0.96 to 1.60, p = 0.10) in patients with PAD. A sensitivity analysis limited to patients with CLI demonstrated that concomitant CAD was associated with significantly higher adjusted rates of both MACCE (adjusted HR 1.52, 95% CI 1.14 to 2.03, p = 0.01) and mortality (adjusted HR 1.64, 95% CI 1.12 to 2.20, p = 0.006). In conclusion, despite higher rates of GDMT use, PAD patients with concomitant CAD had significantly increased risk of all-cause mortality during a 5-year postprocedural follow-up. The subgroup of CLI patients with concomitant CAD was at particularly high risk for both MACCE and all-cause mortality.


t(8;21) (q22;q22) acute myelogenous leukemia in Mexico: a single institution experience.
We analyze the prevalence and clinical features of a group of patients with t(8;21) (q22;q22) acute myeloblastic leukemia, identified in a single institution in México over a 10-year period. Fifteen patients presented at the Centro de Hematología y Medicina Interna de Puebla from February 1995 to August 2005; only nine were treated and followed in the institution. Median age was 24 years, (range 7-49); there was only one male. According to the French-American-British (FAB) morphological classification of leukemia, the morphology was M2 in four cases, M4 in three cases, M3 in one case and M0 in one. In addition to the myeloid markers, lymphoid markers were identified in 6 patients. Patients were induced to remission with combined chemotherapy and three subsequently underwent bone marrow transplantation (BMT). The median overall and disease-free survival has not been reached, being above 3390 days, the probability of survival at this time was 73%. In this single-center experience in México, we found that the t(8;21) (q22;q22) variant of leukemia was more frequent than in Caucasian populations, that the co-expression of lymphoid markers in the blast cells is very frequent and that this malignancy is associated with a relatively good prognosis.


Light-Induced Hydrogel Based on Tumor-Targeting Mesoporous Silica Nanoparticles as a Theranostic Platform for Sustained Cancer Treatment.
Herein, we report a facile fabrication of a polymer (azobenzene and α-cyclodextrin-functionalized hyaluronic acid) and gold nanobipyramids (AuNBs) conjugated mesoporous silica nanoparticles (MSNs) to be used as an injectable drug delivery system for sustained cancer treatment. Because of the specific affinity between the hyaluronic acid (HA) on MSNs and the CD44 antigen overexpressed on tumor cells, the MSNs can selectively attach to tumor cells. The nanocomposite material then exploits thermoresponsive interactions between α-cyclodextrin and azobenzene, and the photothermal properties of gold nanobipyramids, to in situ self-assemble into a hydrogel under near-infrared (NIR) radiation. Upon gelation, the drug (doxorubicin)-loaded MSNs carriers were enclosed in the HA network of the hydrogel, whereas further degradation of the HA in the hydrogel due to the upregulation of hyaluronidase (HAase) around the tumor tissue will result in the release of MSNs from the hydrogel, which can then be taken by tumor cells and deliver their drug to the cell nuclei. This design is able to provide a microenvironment with rich anticancer drugs in, and around, the tumor tissue for time periods long enough to prevent the recrudescence of the disease. The extra efficacy that this strategy affords builds upon the capabilities of conventional therapies.


Development of chronic tests for endocrine active chemicals. Part 2: an extended fish early-life stage test with an androgenic chemical in the fathead minnow (Pimephales promelas).
The Endocrine Modulators Study Group (EMSG) of the European Chemical Industry has proposed an extended fish early-life stage (ELS) test based on OECD test guideline 210 in combination with a fish pair-breeding reproduction study as a possible alternative for fish full life cycle testing. In this paper the androgen methyldihydrotestosterone (MDHT) was tested in an extended ELS test with fathead minnow supplementary to such a test with the weak estrogen 4-tert-pentylphenol (4TPP). Main endpoints were secondary sexual characteristics (SSC), plasma vitellogenin (VTG) induction and gonadal development. Early blastula embryos were exposed to 0, 0.10, 0.32 and 1.0 microgMDHTl(-1) for up to 114 days post-hatch (dph). A batch of fish exposed to 1.0 microg l(-1) was transferred to clean water after 30 or 63 dph for the remainder of the study. Ethinylestradiol (EE2) was included as estrogenic reference substance at 0.01 microg l(-1). Exposure to MDHT had no significant effect on hatching success or survival, but significantly increased the condition factor of fish exposed for 63 and 114 dph (up to 150% of the control). At 63 dph MDHT exposure induced appearance of tubercles on the snout (a male SSC) of more than 80% of fish. Compared to the controls, plasma VTG was not detectable or significantly lower in fish exposed to MDHT at 0.10 microg/l, but not significantly affected at higher MDHT concentrations. Both lower levels of MDHT significantly inhibited the development of female gonads as of 30 dph. Fish exposed to MDHT at 0.32 and 1.0 microg l(-1) showed higher incidences of mixed sex gonads (10-25%) and smaller testes or dysplasia of gonadal tissue. Dysplasia was present in 80% of the fish continuously exposed to 1.0 microg l(-1) up to 114 dph, but reversible when fish were transferred to dilution water. Results indicate that suppression of ovarian development was the most sensitive endpoint for MDHT exposure after 30 dph. Other endpoints (e.g., growth and SSC) required exposure during at least up to 63 dph to yield a significant effect. Androgenic effects on VTG production required even longer exposure, i.e., until sufficient number of females had matured.


Effect of eurycomanone on cytochrome P450 isoforms CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 in vitro.
Eurycomanone, an active constituent isolated from Eurycoma longifolia Jack, was examined for modulatory effects on cytochrome P450 (CYP) isoforms CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 using in vitro assays. The IC50 value was determined to assess the potencies of modulation for each CYP isoform. Our results indicated that eurycomanone did not potently inhibit any of the CYP isoforms investigated, with IC50 values greater than 250 μg/ml. Hence there appears to be little likelihood of drug-herb interaction between eurycomanone or herbal products with high content of this compound and CYP drug substrates via CYP inhibition.


Stature estimation in a contemporary Japanese population based on clavicular measurements using multidetector computed tomography.
The aims of this study was to assess the correlation between stature and clavicular measurements in a contemporary Japanese population using three-dimensional (3D) computed tomographic (CT) images, and to establish regression equations for predicting stature. A total of 249 cadavers (131 males, 118 females) underwent postmortem CT scanning and subsequent forensic autopsy between October 2011 and May 2016 in our department. Four clavicular variables (linear distances between the superior margins of the left and right sternal facets to the anterior points of the left and right acromial ends and between the superior margins of the left and right sternal facets to the left and right conoid tubercles) were measured using 3D CT reconstructed images that extracted only bone data. The correlations between stature and each of the clavicular measurements were assessed with Pearson product-moment correlation coefficients. These clavicular measurements correlated significantly with stature in both sexes. The lowest standard error of estimation value in all, male, and female subjects was 3.62cm (r2=0.836), 3.55cm (r2=0.566), and 3.43cm (r2=0.663), respectively. In conclusion, clavicular measurements obtained from 3D CT images may be useful for stature estimation of Japanese individuals, particularly in cases where better predictors, such as long bones, are not available.


Pleiotrophin and the Expression of Its Receptors during Development of the Human Cerebellar Cortex.
During embryonic and fetal development, the cerebellum undergoes several histological changes that require a specific microenvironment. Pleiotrophin (PTN) has been related to cerebral and cerebellar cortex ontogenesis in different species. PTN signaling includes PTPRZ1, ALK, and NRP-1 receptors, which are implicated in cell differentiation, migration, and proliferation. However, its involvement in human cerebellar development has not been described so far. Therefore, we investigated whether PTN and its receptors were expressed in the human cerebellar cortex during fetal and early neonatal development. The expression profile of PTN and its receptors was analyzed using an immunohistochemical method. PTN, PTPRZ1, and NRP-1 were expressed from week 17 to the postnatal stage, with variable expression among granule cell precursors, glial cells, and Purkinje cells. ALK was only expressed during week 31. These results suggest that, in the fetal and neonatal human cerebellum, PTN is involved in cell communication through granule cell precursors, Bergmann glia, and Purkinje cells via PTPRZ1, NRP-1, and ALK signaling. This communication could be involved in cell proliferation and cellular migration. Overall, the present study represents the first characterization of PTN, PTPRZ1, ALK, and NRP-1 expression in human tissues, suggesting their involvement in cerebellar cortex development.


The Impact of Methamphetamine Use on Trauma Patients at a Level I Trauma Center: A 10-Year Retrospective Review.
The effects of methamphetamines (MAs) on trauma patient outcomes have been evaluated, but with discordant results. The purpose of this study was to identify hospital outcomes associated with MA use after traumatic injury. Retrospective review of adult trauma patients admitted to an American College of Surgeons verified-Level I trauma center who received a urine drug screen (UDS) between January 1, 2004 and December 31, 2013. Logistic regression analysis was used to identify factors associated with mortality. Patients with a negative UDS were used as controls. Among the 2321 patients included, 75.1 per cent were male, 81.9 per cent were white, and the average age was 39. Patients were grouped by UDS results (negative, MA only, other drug plus MA, or other drug without MA). A positive drug screen result of other drug without MA demonstrated a significantly lower risk for mortality, but longer intensive care unit and hospital length of stay, as well as increased ventilator days than negative results. Results of MA only did not alter the risk of mortality. These findings suggest that patients who test positive for MAs are not at an increased risk of in-hospital mortality when compared with patients having a negative drug screen.


Gene therapy for cystic fibrosis.
Cystic Fibrosis (CF) is an autosomal recessive disorder due to mutations in the CF transmembrane conductance regulator (CFTR) gene that lead to defective ion transport in the conducting pulmonary airways and exocrine glands. Through a process that is not fully understood, CFTR defects predispose affected patients to chronic endobronchial infections with organisms such as Pseudomonas aeruginosa and Staphylococcus aureus. Following the discovery of the CFTR gene in 1989, CF became one of the primary targets for gene therapy research. Early enthusiasm surrounded the new field of gene therapy during most of the 1990s and it led academics and clinicians on a big effort to apply gene therapy for cystic fibrosis. Clinical studies have been pursued using recombinant adenovirus, recombinant adeno-associated virus, cationic liposomes, and cationic polymer vectors. Although to this date no dramatic therapeutic benefits have been observed, a lot of information has been gained from the pre-clinical and clinical studies that were performed. This learning curve has led to the optimization of vector technology and an appreciation of immune and mechanical barriers that have to be overcome for successful delivery.


Bryostatin-1 vs. TPPB: dose-dependent APP processing and PKC-α, -δ, and -ε isoform activation in SH-SY5Y neuronal cells.
Activation of the α-secretase processing pathway of amyloid precursor protein (APP) is recognized as an important mechanism which diverts APP processing from production of beta-amyloid (Aβ) to non toxic sAPPα, decreasing Alzheimer's disease (AD) plaque formation and AD-associated cognitive deficits. Two potent classes of PKC modulators can activate the α-secretase pathway, the benzo/indolactams and bryostatin/bryologues. While both modulate PKC-dependent APP processing, no direct comparisons of their relative pharmacological potencies have been accomplished which could assist in the development of AD therapies. In this study, we measured the activation of α-secretase APP processing and PKC-α, -δ, and -ε induced by the benzolactam-APP modulator TPPB and bryostatin-1 in the neuroblastoma cell line SH-SY5Y which expresses APP and α- and β-secretase processing mechanisms. Bryostatin-1 produced a more rapid, potent, and sustained activation of α-secretase APP processing than TPPB and selectively activated PKC-δ and PKC-ε. Although TPPB also activated α-secretase, its potency was approximately 10- to 100-fold lower, possibly reflecting lower PKC-δ and -ε activation. Because bryostatin-1 is a highly potent PKC-δ and -ε activator which activates α-secretase APP processing, further characterization of bryostatin-1/bryologues may help refine their use as important tools for the clinical management of AD.


The molecular basis of sulfonamide resistance in Toxoplasma gondii and implications for the clinical management of toxoplasmosis.
Polymerase chain reaction amplification and DNA sequencing of the Toxoplasma gondii dihydropteroate synthase gene (dhps) identified 4 alleles among parasite populations from 32 cases of human toxoplasmosis. Heterologous expression and enzyme assay reveal that 3 of these alleles encode sulfadiazine (Sdz)-sensitive enzymes. The fourth, generating a highly Sdz-resistant enzyme, differs from 1 of the other 3 at only a single residue (407) of DHPS. Of interest, a fifth allele, found in a laboratory-induced Sdz-resistant line, also differs from another of these 3 drug-sensitive forms by the same single mutation that affects residue 407 of DHPS. Significantly, residues corresponding to DHPS-407 are implicated in sulfonamide resistance in other microorganisms. The human-derived allelic form encoding the Sdz-resistant enzyme was found in T. gondii associated with a fatal infection, and its presence within clinical material may have implications for sulfonamide use, particularly in cases of toxoplasmosis in which the initial response to drug treatment is poor.


The surgical morbidity and mortality meeting as an educational tool.
This study aimed at evaluating the educational value of the morbidity mortality meeting and benefits obtained from it so as to implement changes that can improve it. Surgeons (n = 13) at a university hospital responded anonymously to a questionnaire which was structured to monitor the educational activity of the morbidity mortality meeting. They indicated their perceptions on a five-point scale (very poor, poor, fair, good and very good). Depending on the results of the first questionnaire, these changes were made: 1) Standardisation of the notice of the Meeting 2) Organization of the meeting 3) Review of the literature on the specific problems encountered. The participants were not aware of the results of the first questionnaire. Nine weeks later, the same questionnaire was repeated (n=12). Mann-Whitney test was used to compare the ratings of the two questionnaires. The attributes which showed significant improvement between the first and second questionnaires were a) organization (p = 0.004; (median (range) 3 (2-5) compared with 5 (3-5)) b) knowledge is up-to-date (p < 0.005; (median (range) 3 (2-4) compared with 4 (3-5)), c) discussion related to the problem (0.01; (median (range) 3 (1-4) compared with 4 (3-5)) and d) notice of the meeting (p < 0.026; (median (range) 3 (2-4) compared with 4 (2-5)). This study showed that specific actions can improve the educational quality of the morbidity mortality meeting.


Concentration, Spatial Distribution, Contamination Degree and Human Health Risk Assessment of Heavy Metals in Urban Soils across China between 2003 and 2019-A Systematic Review.
This study provides an overview of the studies of heavy metal pollution regarding As, Cd, Cr, Hg, Pb, Cu, Zn and Ni in the urban soils throughout 71 cities of China, based on data from online literature, during the period 2003-2019. The concentrations, spatial distributions, contamination degrees and health risks of heavy metals in the urban soils were evaluated. The results demonstrated that the mean values of eight heavy metals all exceeded the soil background values in China, and the kriging interpolation method showed that the hot-spot cities with heavy metal contamination in urban soils were mainly concentrated in the southwest, southcentral, southeast coast, northcentral and northwest regions of China. The geoaccumulation index (Igeo) indicated that Hg and Cd were at moderate contamination levels and that the levels of the other six metals did not appear contamination. The pollution index (PI) showed that Cd and Hg reached high contamination levels, and the other metals reached moderate contamination levels. The integrated pollution index (IPI) and potential ecological risk index (PRI) indicated that the integral urban soils in the study areas ranked high contamination levels and moderate ecological risk degree, respectively, and Cd and Hg should be labeled as priority metals for control in the urban soils around China. The human health risk assessments for the heavy metals indicated that ingestion was the dominant exposure pathway for having adverse effects on human health. The mean Hazard index (HI) values of eight heavy metals all showed that adverse effects on human health were unlikely, and the mean carcinogenic (CR) values of As, Cr and Ni for children and adults all suggested an acceptable carcinogenic risk to human beings. In addition, children exposed to these heavy metals faced more serious non-carcinogenic and carcinogenic health threats compared to adults. The results could provide valuable information for demanding the better control of heavy metal pollution and mitigation of the adverse effects on residents by environmental regulators in national urban regions.


[Extracorporeal shock wave therapy in chronic prostatitis].
Chronic prostatitis is a prevalent urologic disease, but treatment outcomes are not always satisfactory. As a rule, chronic prostatitis results in chronic pelvic pain syndrome, significantly reducing the patient's quality of life. Open pilot prospective non-comparative study was conducted to test the effectiveness of extracorporeal shock wave therapy (ESWT) using Aries (Dornier) machine in patients with chronic prostatitis (CP) of IIIb category. A total of 27 patients underwent ESWL as monotherapy, 2 times a week for a course of 6 sessions. Exposure settings: 5-6 energy level (by sensation), the frequency of 5 Hz, 2000 pulses per session; each patient received a total energy up to 12000 mJ. per procedure. Treatment results were evaluated using NIH-CPSI (National Institute of Health Chronic Prostatitis Symptom Index) upon completing the 3 week course of 6 treatments and at 1 month after ESWT. Immediately after the ESWT course positive trend was not significant: pain index decreased from 9.1 to 7.9, urinary symptom score remained almost unchanged (4.2 at baseline, 4.1 after treatment), quality of life index also showed a slight improvement, dropping from 7.2 points to 6.0. Total NIH-CPSI score decreased from 20.5 to 18.0. One month post-treatment pain significantly decreased to 3.2 points, the urinary symptom score fell to 2.7 points, the average quality of life score was 3.9 points. ESWT, performed on Aries (Dornier) machine, is highly effective as monotherapy in patients with category IIIb chronic prostatitis.