Sensitive molecular diagnostic assays to mitigate the risks of asymptomatic bacterial diseases of plants.
Our highly concentrated monoculture makes crops vulnerable to pests and diseases. An increase in emerging non-indigenous bacterial diseases poses a real threat to US agriculture. The United States has 100,000 miles of shoreline and 6,000 miles of border, making possible easy introduction of crop pests and diseases. Most threatening to crops are the cross-domain enteric bacteria. In contrast to animals, crops have hundreds of major diseases and development of molecular-based detection protocols for each pathogen is impossible with current technology. Rathayibacter toxicus, a neurotoxin-producing bacterium transmitted by a seed gall nematode, is an example of a high-risk Select Agent. The bacterium infects seeds of grasses without showing any symptoms, often resulting in the death of grazing cattle. A prerequisite for the control of any disease is sensitive detection and proper identification of the causal organism. Detecting bacteria in samples of plants showing symptoms is relatively simple, whereas detection in asymptomatic tissues is difficult due to the extremely low numbers of the target pathogen present. Rapid serological assays work well with symptomatic tissues but not from asymptomatic tissue when bacteria levels are below sensitivity limits. Classical agar-plating assays are 1,000 fold more sensitive then serology or PCR. However, agar plating assays take from 3 to 5 days and require pathogenicity tests to confirm the identity. PCR-based assays allow for rapid, accurate identification but are insensitive due to use of 1 microL sample in comparison to 100 microL used for agar plating. To overcome this disadvantage, an enrichment technique termed BIO-PCR can be used in combination with agar plating for detection with asymptomatic tissues. The key to developing a successful BIO-PCR protocol is to determine the time required for development of pin point-size colonies to appear. For most plant pathogens 15 to 24 hours is sufficient time, whereas for the cross-domain bacteria only 1 to 2 hours is needed. For greater sensitivity, BIO-PCR can be combined with 96-well microliter plates with membranes to detect a single viable cell per 10 mL of an aqueous sample.


The Sins of the Parents Are to Be Laid Upon the Children: Biased Humans, Biased Data, Biased Models.
Technological innovations have become a key driver of societal advancements. Nowhere is this more evident than in the field of machine learning (ML), which has developed algorithmic models that shape our decisions, behaviors, and outcomes. These tools have widespread use, in part, because they can synthesize massive amounts of data to make seemingly objective recommendations. Yet, in the past few years, the ML community has been drawing attention to the need for caution when interpreting and using these models. This is because these models are created by humans, from data generated by humans, whose psychology allows for various biases that impact how the models are developed, trained, tested, and interpreted. As psychologists, we thus face a fork in the road: Down the first path, we can continue to use these models without examining and addressing these critical flaws and rely on computer scientists to try to mitigate them. Down the second path, we can turn our expertise in bias toward this growing field, collaborating with computer scientists to reduce the models' deleterious outcomes. This article serves to light the way down the second path by identifying how extant psychological research can help examine and curtail bias in ML models.


The future of computers in nursing.
Nursing and computers will enter the new millennium in synergy. As a science, nursing is using computers to organize and communicate information to expedite the nursing process and provide safe patient care. In 1992, the American Nursing Association recognized a new specialty in nursing: Nursing Informatics, a specialty that will provide the ability to adapt to the ever-changing future technology.


Prevalence of fatty liver in a general population of Okinawa, Japan.
A total of 2,574 residents in Yaeyama District of Okinawa, Japan, were investigated using real time ultrasonography to determine the real prevalence of fatty liver in the general population and to define its associated factors. Overall prevalence of fatty liver was 14.0%. Prevalence of fatty liver in persons under 19 years old was only 1.2%, and increased with age to a maximum in persons 40-49 years of age and then decreased. For persons over 20 years old, obesity index and serum levels of triglyceride and total cholesterol were measured, and alcohol consumption was asked. Prevalence of fatty liver was significantly higher in drinkers than non-drinkers (p less than 0.01), and increased with alcohol consumption. Furthermore, in persons not suffering from obesity prevalence of fatty liver was significantly higher in drinkers than in non-drinkers (p less than 0.001). The results of logistic regression analysis indicated that obesity and elevated serum triglyceride level in both sexes, and alcohol in males were significant predictors of fatty liver. In conclusion, prevalence of fatty liver increased with age to a maximum in persons 40-49 years of age and overall was 14.0%. Obesity was the strongest associated factor in both sexes and in males alcohol was also a strong factor.


Microwave spectrum and intramolecular hydrogen bonding of propargyl selenol (HC[triple bond]CCH2SeH).
The microwave spectrum of propargyl selenol, HC[triple bond]CCH(2)SeH, has been investigated in the 19-80 GHz spectral range at -30 degrees C. The spectra of five isotopologues of one conformer, which has a synclinal conformation for the C-C-Se-H link of atoms, were assigned. This conformational preference allows for the formation of a weak intramolecular hydrogen bond between the hydrogen atom of the selenol group and the pi electrons of the triple bond. This hydrogen-bonded conformer is at least 5 kJ/mol more stable than the rotamer having an antiperiplanar conformation for the C-C-Se-H chain. The microwave spectrum clearly shows that the hydrogen atom tunnels between the two mirror-image synclinal forms, but it was not possible to determine the tunneling frequency. The microwave study has been augmented by quantum chemical calculations at the MP2/aug-cc-pVTZ and B3LYP/aug-cc-pVTZ levels of theory. These calculations predict rotational and centrifugal distortion constants that are in good agreement with the experimental counterparts but predict a far too small energy difference of approximately 1.5 kJ/mol for the energy difference between the antiperiplanar and synclinal forms. The conformational properties and internal hydrogen bonding of HC[triple bond]CCH(2)SeH are compared with similar properties of other selenols, which are stabilized by intramolecular hydrogen bonds.


[Sexuality in acute myocardial infarction patients].
We as nurses in the Coronary Unit we do not see the sexuality of the patients sufficiently addressed neither by us nor by the patients themselves. In this article we are trying to analize the reasons and to emphasize the need to include this subject in our Nursing Problem List. In it we explaine the fears and the wrong ideas that we have identified in our patients. The sexual function is not affected by a myocardial infarction but psychological factors, age, drugs and other associated diseases might be a reason. A quiet enviroment, a fit training plan and looking for personalise proper alternatives may help the patient to start a satisfactory sexual life again.


Inhibition of tetrodotoxin (TTX)-resistant and TTX-sensitive neuronal Na(+) channels by the secretolytic ambroxol.
Ambroxol has a long history for the treatment of airway diseases because of its beneficial effects on surfactant synthesis and mucus-modifying properties. Some findings, however, point to an additional effect on neuronal signal transduction: ambroxol can suppress reflexes such as the cough or the corneal reflex. The airways and the cornea are innervated by C-fibers, which express voltage-gated Na(+) channels with and without sensitivity to tetrodotoxin (TTX). In this study, we performed voltage-clamp experiments to investigate whether ambroxol affects these channel types. In rat dorsal root ganglia, TTX-resistant Na(+) currents were suppressed in a concentration-dependent manner with IC(50) values of 35.2 and 22.5 microM for tonic and phasic block, respectively. Depolarizing prepulses increased the potency of ambroxol, and steady-state inhibition curves were shifted to more negative values. The inhibition was not frequency-dependent. TTX-sensitive currents were inhibited with lower potency (approximately 50% inhibition with 100 microM). Recombinant rat brain IIA channels in Chinese hamster ovary cells were blocked with IC(50) values of 111.5 and 57.6 microM for tonic and phasic block, respectively; in contrast to TTX-resistant channels the block was frequency-dependent. Thus, ambroxol indeed blocks neuronal voltage-gated Na(+) channels, and TTX-resistant channels in sensory neurons were more sensitive than TTX-sensitive. Compared with known local anesthetics (e.g., lidocaine or benzocaine), the potency for Na(+) channel block was relatively high. A recent clinical trial has further confirmed that ambroxol relieved pain and was beneficial in patients who suffered from sore throat.


Psychiatric morbidity in pediatric critical illness survivors: a comprehensive review of the literature.
To review the prevalence of psychiatric syndromes in pediatric critical illness survivors as well as to summarize data on vulnerabilities and pediatric intensive care unit exposures that may increase risk of developing these syndromes. MEDLINE (1966-2009), the Cochrane Library (2009, issue 3), and PsycINFO (1967-2009) as of August 9, 2009. Case-control, cross-sectional, prospective cohort and retrospective cohort studies as well as randomized controlled trials. Hospitalization for the treatment of a critical illness. Assessments of psychiatric symptoms/disorders at least once after discharge. Seventeen studies were eligible. The most commonly assessed psychiatric disorders were posttraumatic stress disorder and major depression. The point prevalence of clinically significant posttraumatic stress disorder symptoms ranged from 10% to 28% (5 studies). The point prevalence of clinically significant depressive symptoms ranged from 7% to 13% (2 studies). Preillness psychiatric and/or developmental problems and parental psychopathology were associated with vulnerability to psychiatric morbidity. Neither age nor sex of a child consistently increased vulnerability to postillness psychopathology. Exposure to increased severity of medical illness and pediatric intensive care unit service-delivery characteristics (eg, invasive procedures) were predictors of psychiatric illness in some but not all studies. Early postillness psychiatric symptoms were predictors of later psychiatric morbidity. Psychiatric morbidity appears to be a substantial problem for pediatric critical illness survivors. Future research should include more in-depth assessment of post-critical illness depressive, anxiety, and psychotic symptoms, validate existing psychiatric instruments, and clarify how vulnerability factors, pediatric intensive care unit service-delivery characteristics, and severity of critical illnesses are associated with subsequent psychopathology.


Micro-origin of no-trough trapping in self-excited nonlinear dust acoustic waves.
We experimentally investigate the micro-origin of the absence of trough trapping in nonlinear traveling dust acoustic waves self-excited by the downward ion flow in the dissipative dusty plasma. The wave forms of dust density, the drag force from the background neutrals, ions, and dusts, and the effective potential energy for dusts are constructed by tracking dust motion and measuring the velocity and the position-dependent forces. The tilted washboard type potential wave form with a slight phase lead to the dust density wave form is obtained. It provides sufficient kinetic energy to compensate drag dissipation and move dusts from the dust density trough to the crest front. The dusts with sufficient energy overcome the downward pushing by the crest front, climb over the crest, and sustain the oscillatory motion with upward drift. Those dusts with insufficient energy to climb over the potential barrier of the crest are trapped in and move downward with the crest front, until kicked upward by fluctuation. The upward neutral dominated drag force prevents them from sliding down the potential energy hill at the crest front and further oscillating in the trough. It leads to the absence of trough trapping.


Antiarrhythmic effects of optical isomers of cibenzoline on canine ventricular arrhythmias.
Antiarrhythmic effects of (+)-cibenzoline and (-)-cibenzoline were examined using two canine ventricular arrhythmia models. Digitalis arrhythmia, which is suppressed by Na channel blockers, was induced by intermittent intravenous (i.v.) injection of ouabain in pentobarbital-anesthetized dogs. Adrenaline arrhythmia, which is suppressed by Ca channel blockers, was induced by adrenaline infusion in halothane-anesthetized dogs. Ten and 5 mg/kg i.v. (+)-cibenzoline suppressed digitalis- and adrenaline-induced arrhythmias, respectively. The minimum effective plasma concentrations of (+)-cibenzoline for digitalis- and adrenaline-induced arrhythmias were 1.4 +/- 0.4 and 2.0 +/- 0.6 micrograms/ml, respectively (mean +/- SD, n = 6). A lower dose of 1 mg/kg i.v. of (-)-cibenzoline suppressed the digitalis-induced arrhythmia, whereas 5 mg/kg i.v. was needed to suppress adrenaline-induced arrhythmias. The minimum effective plasma concentrations of (-)-cibenzoline for digitalis- and adrenaline-induced arrhythmia were 0.06 +/- 0.04 and 0.7 +/- 0.1 micrograms/ml, respectively (mean +/- SD, n = 6). The stronger antiarrhythmic effect of (-)-cibenzoline indicates that (-)-isomer may have an effect nearly 5-20 times stronger in suppressing Na channels, but effects of both drugs on Ca channels may be almost equipotent.


Ultrafast population switching of quantum dots in a structured vacuum.
We demonstrate picosecond, high-contrast population flipping of two-level atoms interacting with femtojoule optical pulses in a 3D photonic band gap waveguide. This is the result of giant Mollow splitting caused by strong light localization and a remarkable field-dependent relaxation of the atomic Bloch vector as it evolves near an abrupt jump in the electromagnetic density of states. Unlike steady-state switching, population inversion can remain nearly complete after the pulse subsides. This may be used for multiwavelength channel, all-optical, on-chip information processing.


Empirical determination of the harmonic force constants in benzene. 4. The Fermi resonances.
In this article, we present a continuation of our work on the refinement of the harmonic force constants Fi,k in benzene (in symmetrized Whiffen's coordinates) and on a growing number of higher order (anharmonic) force constants, Fi,j,k and Fi,j,k,l, that are of importance for the benzene isotopomer invariant potential energy surface. The refined set of harmonic and anharmonic force constants improves the agreement between the experimental levels and those calculated theoretically. The emphasis of the present work is on the analysis of the two notable Fermi resonances in benzene (nu8 +nnu1 <=> (n +1)nu1 + nu6, where n = 0, 1, ... m, and nu20 <=> nu8 + nu19 <=> nu1 + nu6 + nu19). For this purpose, we have further extended our fully dimensional, fully symmetrized, and nonperturbative vibrational procedure to the vibrational structure of the benzene isotopic species with D6h symmetry.


Multiplex fatty acid imaging inside cells by Raman microscopy.
Visualizing intracellular fatty acids (including free and esterified form) is very useful for understanding how and where such molecules are incorporated, stored, and metabolized within cells. However, techniques of imaging multiple intracellular fatty acids have been limited by their small size, making it difficult to label and track without changing their biological and biophysical characteristics. Here, we present a new method for simultaneously visualizing up to five atomically labeled intracellular fatty acid species. For this, we utilized the distinctive Raman spectra depending on the labeling patterns and created a new, extensible opensource software to perform by-pixel analysis of extracting original spectra from mixed ones. Our multiplex imaging method revealed that fatty acids with more double bonds tend to concentrate more efficiently at lipid droplets. This novel approach contributes to reveal not only the spatial dynamics of fatty acids, but also of any other metabolites inside cells.


Effect of intraluminal pH on cholesterol and oleic acid absorption from micellar solutions in the rat.
We have studied the effects of intraluminal pH on micellar solubilization and on absorption rate of oleic acid (OA) and cholesterol in proximal small bowel segments and the total small bowel in rats. In addition, pH effect on fecal excretion of [3H]cholesterol was studied over a period of 4 days after duodenal administration of cholesterol in solutions at different pH using beta-sitosterol as a nonabsorbable marker. Rates of absorption of OA and cholesterol were, respectively, 1.8 and 1.9 times higher at pH 5.5 in both proximal bowel segments as compared with pH 6.5 (P less than 0.001). Similar observations were made when the whole small bowel was perfused. At pH 5.5, 1.8 times more OA was absorbed and 1.5 times more cholesterol than at pH 6.5 (P less than 0.001). Also, fecal output of radioisotope following administration of pH 5.5 solution was only 47% of the excretion using the pH 6.5 solution. Excretion of beta-sitosterol, which serves as a nonabsorbable marker, was not affected by pH differences. In vitro measurements of micellar solubility at the two pH levels by ultracentrifugation showed that an increase of one pH unit resulted in a decreased number of particles in the oil phase (oleic acid and cholesterol in the emulsified particles in pH 6.5 solution is 37 and 34%, respectively, of that in the pH 5.5 solution) due to increased solubilization into the micellar phase. Measurements of monomer activities of OA and cholesterol using a polyethylene disk technique showed a significantly higher activity at the lower pH.(ABSTRACT TRUNCATED AT 250 WORDS)


Prognostic usefulness of white blood cell count on admission and one-year outcome in patients with non-ST-segment elevation acute chest pain.
Little is known about the prognostic value of leukocyte count on admission for patients with chest pain. In total, 1,461 patients who presented to the emergency department with non-ST-segment elevation chest pain were studied by clinical history, electrocardiography, serial troponin I determination, and leukocyte count on admission. End points were 1-year mortality and major events (mortality or infarction). Overall patient distribution by quartiles of leukocyte count showed increased mortality (6%, 7%, 6%, and 17%, p = 0.0001) and major events (13%, 13%, 15%, and 24%, p = 0.0001) in the fourth quartile. After adjustment for other risk factors, the fourth quartile cut-off value (>10,000 cells/ml) predicted mortality (hazard ratio 2.0, 95% confidence interval 1.4 to 2.8, p = 0.0001) but not major events (p = 0.07). When analysis was performed to assess troponin status, in the subgroup with increased troponin (n = 634, 16% mortality), a leukocyte count >10,000 cells/ml was related to mortality (hazard ratio 2.2, 95% confidence interval 1.5 to 3.4, p = 0.0001). However, in the subgroup with normal troponin levels (n = 827, 4.2% mortality), there were no differences in mortality between patients with or without a leukocyte count >10,000 cells/ml (4.4% vs 4.2%, p = 0.8), with survival curves showing a tight overlap (p = 0.9). Further, in the subgroup with normal troponin levels, leukocyte count was not significantly different between patients with or without ST depression (7,969 +/- 2,171 vs 8,108 +/- 2,356 cells/ml, p = 0.6) and was not associated with mortality in patients with ST depression (p = 0.7). In conclusion, leukocyte count on admission is predictive of mortality in patients with chest pain and non-ST-segment elevation myocardial infarction. However, in the absence of myocardial necrosis, leukocyte count lacks prognostic value.


Efficacy and safety of bortezomib maintenance in patients with newly diagnosed multiple myeloma: a meta-analysis.
Multiple myeloma (MM) is a B-cell neoplasm with a high incidence of relapse. Bortezomib has been extensively studied for the maintenance treatment of MM. Here, we carried out a meta-analysis to determine the efficacy and safety of maintenance therapy with bortezomib. We searched for clinical trials in PubMed (Medline), Embase (OVID), and the Cochrane Library. Two randomized controlled trials (RCTs) enrolling a total of 1338 patients were included. Bortezomib maintenance statistically significantly improved both progression-free survival (PFS) (hazard ratio (HR) 0.67, 95% confidence interval (CI) = 0.51 to 0.87, P=0.003) and overall survival (OS) (HR = 0.75 therapy, 95% CI = 0.63 to 0.89, P=0.001) more than did non-bortezomib maintenance therapy. Our analysis revealed higher incidence of neutropenia (risks ratios (RR) = 1.39; 95% CI = 1.08 to 1.79), peripheral neuropathy (PN) (RR = 2.23; 95% CI = 1.38 to 3.61, P=0.001), and cardiologic events (RR = 1.91; 95% CI = 1.12 to 3.28, P=0.02) in patients with bortezomib maintenance therapy. Our meta-analysis demonstrates OS and PFS benefits of bortezomib maintenance therapy in patients with newly diagnosed MM. However, the therapy is associated with increased risk of adverse events. Additionally, more RCTs are needed for better understanding and determination of optimal bortezomib maintenance therapy in MM.


Crystal structure of human CD38 extracellular domain.
Human CD38 is a multifunctional protein involved in diverse functions. As an enzyme, it is responsible for the synthesis of two Ca2+ messengers, cADPR and NAADP; as an antigen, it is involved in regulating cell adhesion, differentiation, and proliferation. Besides, CD38 is a marker of progression of HIV-1 infection and a negative prognostic marker of B-CLL. We have determined the crystal structure of the soluble extracellular domain of human CD38 to 1.9 A resolution. The enzyme's overall topology is similar to the related proteins CD157 and the Aplysia ADP-ribosyl cyclase, except with large structural changes at the two termini. The extended positively charged N terminus has lateral associations with the other CD38 molecule in the crystallographic asymmetric unit. The analysis of the CD38 substrate binding models revealed two key residues that may be critical in controlling CD38's multifunctionality of NAD hydrolysis, ADP-ribosyl cyclase, and cADPR hydrolysis activities.


Physician ownership of specialty spine hospitals.
Patients expect and deserve quality medical care. Physicians, by nature, want what is best for their patients. With the advent of specialty hospitals, physicians can own, run, and control a superior center designed to deliver the highest quality health care. Neurosurgeons who manage their own hospital may set the standards for medical excellence, with patient satisfaction as their primary focus.


Diagnostic and Therapeutic Role of Extracellular Vesicles in Articular Cartilage Lesions and Degenerative Joint Diseases.
Two leading contributors to the global disability are cartilage lesions and degenerative joint diseases, which are characterized by the progressive cartilage destruction. Current clinical treatments often fail due to variable outcomes and an unsatisfactory long-term repair. Cell-based therapies were once considered as an effective solution because of their anti-inflammatory and immunosuppression characteristics as well as their differentiation capacity to regenerate the damaged tissue. However, stem cell-based therapies have inherent limitations, such as a high tumorigenicity risk, a low retention, and an engraftment rate, as well as strict regulatory requirements, which result in an underwhelming therapeutic effect. Therefore, the non-stem cell-based therapy has gained its popularity in recent years. Extracellular vesicles (EVs), in particular, like the paracrine factors secreted by stem cells, have been proven to play a role in mediating the biological functions of target cells, and can achieve the therapeutic effect similar to stem cells in cartilage tissue engineering. Therefore, a comprehensive review of the therapeutic role of EVs in cartilage lesions and degenerative joint diseases can be discussed both in terms of time and favorability. In this review, we summarized the physiological environment of a joint and its pathological alteration after trauma and consequent changes in EVs, which are lacking in the current literature studies. In addition, we covered the potential working mechanism of EVs in the repair of the cartilage and the joint and also discussed the potential therapeutic applications of EVs in future clinical use.


Barriers to and facilitators of health services utilisation by refugees in resettlement countries: an overview of systematic reviews.
Objective The aim of this study was to provide an overview of the previously reviewed research literature to identify barriers and facilitators to health service utilisation by refugees in resettlement countries. Methods An overview of systematic reviews was conducted. Seven electronic databases (Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, ProQuest Central, Scopus, EBSCO and Google Scholar) were searched for systematic reviews of barriers and facilitators to health-seeking behaviour and utilisation of health services by refugees following resettlement. The two authors independently undertook data selection, data extraction and quality assessment using a validated tool. Results Nine systematic reviews covered a range of study areas and refugee populations. Barriers to health service utilisation fell into three broad areas: (1) issues related to refugees, including refugee characteristics, sociocultural factors and the effects of previous experiences; (2) issues related to health services, including practice issues and the knowledge and skills of health professionals; and (3) issues related to the resettlement context, including policies and practical issues. Few facilitators were identified or evaluated, but these included approaches to care, health service responses and behaviours of health professionals. Conclusions Barriers to accessing health care include refugee characteristics, practice issues in health services, including the knowledge and skills of health professionals, and the resettlement context. Health services need to identify barriers to culturally sensitive care. Improvements in service delivery are needed that meet the needs of refugees. More research is needed to evaluate facilitators to improving health care accessibility for these vulnerable groups. What is known about the topic? Refugee health after resettlement is poor, yet health service use is low. What does this paper add? Barriers to accessing health services in resettlement countries are related not only to refugees, but also to issues regarding health service practices and health professionals' knowledge and skill, as well as the context of resettlement. Few facilitators to improving refugee access to health services have been identified. What are the implications for practitioners? The barriers associated with health professionals and health services have been linked to trust building, and these need to be addressed to improve accessibility of care for refugees.


Enhancer-core-promoter specificity separates developmental and housekeeping gene regulation.
Gene transcription in animals involves the assembly of RNA polymerase II at core promoters and its cell-type-specific activation by enhancers that can be located more distally. However, how ubiquitous expression of housekeeping genes is achieved has been less clear. In particular, it is unknown whether ubiquitously active enhancers exist and how developmental and housekeeping gene regulation is separated. An attractive hypothesis is that different core promoters might exhibit an intrinsic specificity to certain enhancers. This is conceivable, as various core promoter sequence elements are differentially distributed between genes of different functions, including elements that are predominantly found at either developmentally regulated or at housekeeping genes. Here we show that thousands of enhancers in Drosophila melanogaster S2 and ovarian somatic cells (OSCs) exhibit a marked specificity to one of two core promoters--one derived from a ubiquitously expressed ribosomal protein gene and another from a developmentally regulated transcription factor--and confirm the existence of these two classes for five additional core promoters from genes with diverse functions. Housekeeping enhancers are active across the two cell types, while developmental enhancers exhibit strong cell-type specificity. Both enhancer classes differ in their genomic distribution, the functions of neighbouring genes, and the core promoter elements of these neighbouring genes. In addition, we identify two transcription factors--Dref and Trl--that bind and activate housekeeping versus developmental enhancers, respectively. Our results provide evidence for a sequence-encoded enhancer-core-promoter specificity that separates developmental and housekeeping gene regulatory programs for thousands of enhancers and their target genes across the entire genome.


Phenolic-rich extract of Nopalea cochenillifera attenuates gastric lesions induced in experimental models through inhibiting oxidative stress, modulating inflammatory markers and a cytoprotective effect.
Nopalea cochenillifera (Cactaceae), popularly known as "palma" or "palma doce", is from Mexico, but it was widely introduced in Brazil through crops. It has been used as food and in traditional medicine and is a good source of phenolic compounds. In this study the phytochemical profile and gastroprotective activity of phenolic-rich extract of N. cochenillifera in acute gastric lesion models induced by ethanol and indomethacin were evaluated. High-performance liquid chromatography coupled with mass spectrometry (HPLC/ESI/MSn) allowed the characterization of 12 compounds such as sugars, phenolics and flavonoids. Among polyphenols, the main peak was assigned to isorhamnetin-3-O-(2'',3''-O-di-rhamnose)-glucoside. The TPC and TFC in the dry extract were 67.85 mg of gallic acid equivalent per g/extract and 46.16 mg quercetin equivalent per g/extract, respectively. In the in vitro MTT assay, the extract showed no cytotoxicity and suppressed ROS levels in LPS-treated RAW 264.7 cells. Preclinical models in rats showed that a dose of 100 mg kg-1 (p < 0.0001) in the ethanol model and doses of 100 mg kg-1 (p < 0.5) and 200 mg kg-1 (p < 0.01) in the indomethacin model reduced the gastric lesions. Also, the extract reduced the MPO, MDA, TNF-α and IL-1β levels and increased the GSH and IL-10 levels. The pre-treatment with the extract led to the upregulation of SOD and the downregulation of COX-2 by immunohistochemical analysis. It also showed a cytoprotective effect in the histopathological analysis and stimulated the restoration of the mucus content as observed in the periodic acid-Schiff analysis without modifying the pH, volume or total acidity of the gastric juice. Taken together, N. cochenillifera extract can be applied as a novel gastroprotective ingredient for food or pharmaceutical products.


Gradual changes of ECG waveform during and after exercise in normal subjects.
The directions and magnitudes of time-normalized P, QRS, and ST vectors, and other ECG parameters were analyzed during and after multistage exercise in 56 ostensibly healthy men aged 23 to 62. By selective averaging with a digital computer system a single representative beat was obtained from each stage. Measurements were taken from this beat. During exercise, the interval between the spatial maximum of the P wave and the onset of the QRS complex decreased while the magnitude of the P wave increased. The direction of the P vectors did not change. This pattern corresponds to the electrocardiographic manifestations of predominant right atrial overload. No significant changes in the QRS duration were observed. Also the magnitude and spatial orientation of the maximum QRS vectors remained constant. The interval between the QRS onset and the maximum spatial magnitude of the T wave shortened. The terminal QRS vectors and the ST vectors gradually shifted toward the right, and superiorly. The T magnitude lessened during exercise. In the first minute of the recovery period the P and T magnitudes markedly increased. Afterward all measurements gradually returned to the resting level. Mechanisms which may explain the observed ECG changes during and after exercise are discussed, including changes in the blood conductivity and intracardiac blood volume. Age did not contribute to the variance of the ECG measurements, but a significant reduction of this variance could be otained in some ST-segment measurements by relating them to heart rate with linear regression equations (P less than or equal to 0.05). Therefore it is expected that the sensitivity of the exercise ECG for detection of ischemic heart disease would be increased when heart rate dependent normal limits for ST-segment measurements are used. Different criteria should be employed for the interpretation of the ECG during and after exercise.


[Symptomatology and diagnosis of the diabetic foot].
In the diabetic foot, the vascular component was recently considered as the most important in its pathogenesis. The contribution of the neuropathy was under evaluated, most of the time. However, in the last few years, the neuropathic modifications rank first and the micro- and macro-angiopathies are considered more and more as complicating components. Along with sensory and motor neuropathies, the so-called neuropathic edema is an important symptom. This edema, hot most of the time, is caused by a paralysis of the sympathetic nerve fibres, causing an increased Arterio-venous "shunt", at the expense of the capillary nutritive blood circulation. Orthostasis components and he possible presence of venous insufficiency aggravate he edema. The influence of cardiac components must be excluded. Besides, the likelihood of a venous thrombosis is not increased in diabetic patients. A multi-disciplinary approach is advocated in the diabetic foot.


Hyperbaric Oxygen Preconditioning Provides Preliminary Protection Against Doxorubicin Cardiotoxicity.
Doxorubicin (DOX) is generally recognized to have important cardiotoxic side effects. Studies are contradictory about the interaction between hyperbaric oxygen (HBO2) therapy and doxorubicin-induced cardiomyotoxicity. Recent data suggests that HBO2 therapy can lead to preconditioning of myocardium while generating oxidative stress. Herein we have investigated the effect of HBO2 therapy in a DOX-induced cardiomyocyte injury animal model. Twenty-one rats were divided into three equal groups as follows: 1) Group 1 is a control group (without any intervention), used for evaluating the basal cardiac structures and determining the normal value of cardiacs and serum oxidative markers; 2) Group 2 is the doxorubicin group (single dose i.p. 20 mg/kg doxorubicin) for detecting the cardiotoxic and systemic effects of doxorubicin; 3) Group 3 is the doxorubicin and HBO2 group (100% oxygen at 2.5 atmospheric for 90 minutes, daily), for evaluating the effect of HBO2 in doxorubicin induced cardiotoxicity. At the end of the protocols, the hearts were harvested and blood samples (2 ml) were obtained. The doxorubicin treated animals (Group 2) had increased oxidative stress markers (both cardiac and serum) and severe cardiac injury as compared to the basal findings in the control group. Nevertheless, the highest cardiac oxidative stress index was detected in Group 3 (control vs. Group 3, p = 0.01). However, histological examination revealed that cardiac structures were well preserved in Group 3 when compared with Group 2. Our results suggest that HBO2 preconditioning appears to be protective in the doxorubicin-induced cardiotoxicity model. Future studies are required to better elucidate the basis of this preconditioning effect of HBO2.


Tripleurin XIIc: Peptide Folding Dynamics in Aqueous and Hydrophobic Environment Mimic Using Accelerated Molecular Dynamics.
Peptaibols are a special class of fungal peptides with an acetylated N-terminus and a C-terminal 1,2-amino alcohol along with non-standard amino acid residues. New peptaibols named tripleurins were recently identified from a strain of the filamentous fungal species Trichoderma pleuroti, which is known to cause green mould disease on cultivated oyster mushrooms. To understand the mode of action of these peptaibols, the three-dimensional structure of tripleurin (TPN) XIIc, an 18-mer peptide, was elucidated using an enhanced sampling method, accelerated MD, in water and chloroform solvents. Non-standard residues were parameterized by the Restrained Electrostatic Potential (RESP) charge fitting method. The dihedral distribution indicated towards a right-handed helical formation for TPN XIIc in both solvents. Dihedral angle based principal component analysis revealed a propensity for a slightly bent, helical folded conformation in water solvent, while two distinct conformations were revealed in chloroform: One that folds into highly bent helical structure that resembles a beta-hairpin and another with an almost straight peptide backbone appearing as a rare energy barrier crossing event. The hinge-like movement of the terminals was also observed and is speculated to be functionally relevant. The convergence and efficient sampling is addressed using Cartesian PCA and Kullback-Leibler divergence methods.


[Study on calcium absorption rate in premenarche Chinese girls aged 9 - 11.5 years].
To investigate the characteristics of calcium metabolism in relation to different levels of dietary calcium intakes in premenarche Chinese girls. Forty-nine healthy premenarche girls of Han ethic (9 - 11.5 years) were recruited, and divided into four groups respectively, receiving four different doses of calcium intakes for 6 days, 600 mg (usual diet), 900 mg (containing 250 ml of milk), 1200 mg (containing 250ml of milk and 750 mg of calcium carbonate) and 1500mg calcium (250 ml of milk and 1500 mg of calcium carbonate) per day. A 3-day urine and stool, and a 3-d duplicated food samples were collected to assess the calcium excretion in urine and feces and input of the dietary calcium during the treatment period. There were no significant differences in appearance calcium absorption among the four groups (55%, 53%, 52% and 52%). Urine calcium is correlated negatively with dietary protein and dietary phosphorus. And no correlation was found between dietary protein and calcium absorption. The appearance calcium absorption was (53 +/- 0.12) % in Chinese premenarche girls with dietary calcium intakes ranged between 800 to 1600 mg/d, high dietary protein intakes increase urine calcium secrete.


Shape optimization of acoustic horns using the multimodal method.
This paper presents a method for the shape optimization of an acoustic horn with respect to the impedance matching property based on the discrete multimodal method. The method models the horn as a series of short cylinders and takes mode coupling across the discontinuities into account. The optimization employs a gradient-based algorithm, and allows for analytical derivation of the objective function and its gradient in a numerically workable manner. A case study followed with an experimental validation is presented. With appropriate parameter settings, the method is capable of rapidly finding a smooth and convex horn design that behaves like a high-pass radiator with near-ideal wideband transmission in small dimensions.


Curcumin/Liposome Nanotechnology as Delivery Platform for Anti-inflammatory Activities via NFkB/ERK/pERK Pathway in Human Dental Pulp Treated With 2-HydroxyEthyl MethAcrylate (HEMA).
Curcumin, primary component of the spice turmeric extracted from the rhizomes of Curcuma longa, represents the major anti-oxidant and anti-inflammatory substance found in turmeric, acting thought various mechanisms not completely understood. Curcumin modulates cytokines, growth factors, transcription factors, inflammatory molecules and cell signaling pathways. During restorative dentistry practice, free resin monomers of 2-hydroxyethyl methacrylate (HEMA) propagate through dentin micro-channel and pulp into the bloodstream affecting cellular integrity. The study highlights the significance of application of curcumin bioactive component into liposomal formulations (CurLIP) to restore the homeostasis of dental pulp stem cells (hDPSCs) in response to 3 and 5 mmol L-1 HEMA treatment. Cell proliferation in combination with changes of the morphological features, proinflammatory cytokines secretion as Interleukin (IL) 6, IL8, Monocyte Chemoattractant Protein-1 (MCP1) and Interferon-gamma (IFNγ) were assayed along with the nuclear factor (NF)-kB, an inducible transcription factor involved in the activation of several cell processes associated to extracellular signal-regulated kinases (ERK) and posphorylated (p-) ERK pathway. Our results showed a decreased cell proliferation, morphological changes and upregulation of IL6, IL8, MCP1 and IFNγ in presence of 3 and 5 mmol L-1 HEMA treatment. CurLIP therapy in hDPSCs provokes an increase in cell proliferation and the block of inflammatory cytokines secretion through the inhibitory regulation of NFkB/ERK and pERK signaling cascade. The natural nanocarrier CurLIP influences numerous biochemical and molecular cascades causing anti-inflammatory properties in response to HEMA treatment in human dental pulp stem cells, representing an innovative endodontic formulation able to improve the quality of dental care with a major human community impact.


Experimental design of Fenton and photo-Fenton reactions for the treatment of cellulose bleaching effluents.
Multivariate experimental design was applied to the treatment of a cellulose conventional bleaching effluent in order to evaluate the use of the Fenton reagent under solar light irradiation. The effluent was characterised by the general parameters total organic carbon (TOC), chemical oxygen demand and color, and it was analysed for chlorinated low molecular weight compounds using GC-MS. The main parameters that govern the complex reactive system: Fe(II) and H(2)O(2) initial concentration, and temperature were simultaneously studied. Factorial experimental design allowed to assign the weight of each variable in the TOC removal after 15 min of reaction. Temperature had an important effect in the organic matter degradation, especially when the ratio of Fenton reagents was not properly chosen. Fenton reagent under solar irradiation proved to be highly effective for these types of wastewaters. A 90% TOC reduction was achieved in only 15 min of treatment. In addition, the GC-MS analysis showed the elimination of the chlorinated organic compounds initially detected in the studied bleaching effluents.


NO donor SIN-1 protects against reoxygenation-induced cardiomyocyte injury by a dual action.
It was investigated whether morpholinosydnonimine (SIN-1), which spontaneously decomposes into NO and 3-morpholinoiminoacetonitrile (SIN-1C), can be used for protection of cardiomyocytes against reoxygenation-induced hypercontracture. Isolated ventricular cardiomyocytes (from adult rats) were used as the experimental model. SIN-1 [concentration with half-maximal effect (EC50) 2.5 x 10(-4) M] and SIN-1C (EC50 8.3 x 10(-3) M) inhibited the contractile response of electrically paced cardiomyocytes. When the cells were submitted to substrate-free anoxia (135 min) and subsequent reoxygenation (30 min), the onset of reoxygenation provoked their hypercontracture. It was studied whether the temporary presence of the test agents during the last 15 min of anoxia and the first 15 min of reoxygenation prevented hypercontracture. At 10 nM, SIN-1 prevented hypercontracture in 96% of the cells and SIN-1C in 72% of the cells. The protective effect of SIN-1 was reduced to that of SIN-1C by simultaneous presence of methylene blue (50 microM). Methylene blue had no influence on the protective action of SIN-1C. SIN-1C (10 mM) plus sodium nitroprusside (another NO donor, 250 microM) provided the same degree of protection as SIN-1 (10 mM). The results show that reoxygenation-induced hypercontracture can be prevented or attenuated by the temporary presence of high concentrations of SIN-1 or SIN-1C. SIN-1 acts through a dual mechanism, protecting through the generation of NO and SIN-1C.


RNA-Seq investigations of human post-mortem trigeminal ganglia.
Background The trigeminal ganglion contains neurons that relay sensations of pain, touch, pressure, and many other somatosensory modalities to the central nervous system. The ganglion is also a reservoir for latent herpes virus 1 infection. To gain a better understanding of molecular factors contributing to migraine and headache, transcriptome analyses were performed on postmortem human trigeminal ganglia. Methods RNA-Seq measurements of gene expression were conducted on small sub-regions of 16 human trigeminal ganglia. The samples were also characterized for transcripts derived from viral and microbial genomes. Herpes simplex virus 1 (HSV-1) antibodies in blood were measured using the luciferase immunoprecipitation assay. Results Observed molecular heterogeneity could be explained by sampling of anatomically distinct sub-regions of the excised ganglia consistent with neurally-enriched and non-neural, i.e. Schwann cell, enriched subregions. The levels of HSV-1 transcripts detected in trigeminal ganglia correlated with blood levels of HSV-1 antibodies. Multiple migraine susceptibility genes were strongly expressed in neurally-enriched trigeminal samples, while others were expressed in blood vessels. Conclusions These data provide a comprehensive human trigeminal transcriptome and a framework for evaluation of inhomogeneous post-mortem tissues through extensive quality control and refined downstream analyses for RNA-Seq methodologies. Expression profiling of migraine susceptibility genes identified by genetic association appears to emphasize the blood vessel component of the trigeminovascular system. Other genes displayed enriched expression in the trigeminal compared to dorsal root ganglion, and in-depth transcriptomic analysis of the KCNK18 gene underlying familial migraine shows selective neural expression within two specific populations of ganglionic neurons. These data suggest that expression profiling of migraine-associated genes can extend and amplify the underlying neurobiological insights obtained from genetic association studies.


Acute pancreatitis complicated with splenic rupture: A case report.
Atraumatic splenic rupture is an uncommon complication of acute pancreatitis. This report describes the case of a 30-year-old man with acute pancreatitis and splenic vein thrombosis complicated by splenic rupture. The patient was admitted to the emergency department with pain in the upper abdomen that had been present for six hours and was associated with vomiting and sweating. He was diagnosed with acute pancreatitis of alcoholic etiology. Upon computed tomography (CT) of the abdomen, the pancreatitis was scored as Balthazar C grade, and a suspicious area of necrosis affecting 30% of the pancreas with splenic vein thrombosis was revealed. Seventy-two hours after admission, the patient had significant improvement in symptoms. However, he showed clinical worsening on the sixth day of hospitalization, with increasing abdominal distension and reduced hemoglobin levels. A CT angiography showed a large amount of free fluid in the abdominal cavity, along with a large splenic hematoma and contrast extravasation along the spleen artery. The patient subsequently underwent laparotomy, which showed hemoperitoneum due to rupture of the splenic parenchyma. A splenectomy was then performed, followed by ultrasound-guided percutaneous drainage.


Pregnancy and natural delivery following magnetic resonance imaging-guided focused ultrasound surgery of uterine myomas.
This report discusses a pregnancy case following a series of two consecutive magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) procedures for the treatment of two different myomas in an individual patient. Both procedures were completed without adverse events, and the patient conceived naturally four months after treatment. At 39 weeks, she gave birth to a healthy baby girl, via a vaginal delivery. There were no complications in the pregnancy or during labor.


Providing palliative care for newborns.
Palliative care principles may be applied in the NICU, may be necessary, and may benefit from the contributions of community pediatricians who have a relationship with families undergoing these tragic circumstances. Clinicians across varied disciplines can cooperate to provide an environment in the delivery room or NICU where palliative care can be integrated into patient and family care plans regardless of whether the treatment goal is obtaining a cure, prolonging life, or exclusively palliation and comfort until an expected death. Regardless of the site of care, the best interests of the patient remain the focus of such care. This care should be consistent with the goals and preferences of the family, and respectful of their culture and faith traditions. The physical comfort of the infant and the emotional, psychosocial, and spiritual well-being of his/her family (including siblings and grandparents) all require active management and support. Finally, bereavement support should be provided following an infant's death to help families integrate their loss into their lives.


Naming the Dead: What information do Physical Therapy and Physician Assistant Anatomy Faculty Share With Students?
In this novel study, the researchers quantify cadaver information provided to Physical Therapy (PT) and Physician Assistant (PA) anatomy faculty and ask what portion of that information is then shared with students. Descriptive statistics were used to the describe demographics of the study respondents and to report survey responses. The majority (60% or greater) of faculty who teach anatomy to PT and PA students have clinical degrees matching the student groups they teach. Chi-square analysis showed no appreciable difference (P < 0.001) between PT and PA anatomy faculty in the amount of cadaver information they receive or then share with students. There was a difference in the type of cadaver information (identifying vs. non-identifying) that is received and then shared by these faculty. Faculty are more likely to receive non-identifying cadaver information (93%) than identifying information (40%) (P < 0.0001) and share non-identifying information (83%) than identifying information (26%) with students (P < 0.0003). Interestingly, there is no consensus as to whether sharing cadaver information is respectful or disrespectful to those who donate their bodies for anatomy education and research. Further research is warranted into the reasons anatomy faculty withhold cadaver information from students and in the value, if any, for students knowing more about the cadavers they are learning from.


Brain magnetic resonance imaging in acute optic neuritis. Experience of the Optic Neuritis Study Group.
Changes in the brain on magnetic resonance images are common in patients with optic neuritis even when there is no other clinical evidence of multiple sclerosis. The current study was designed to determine systematically the prevalence of brain abnormalities on magnetic resonance images in the patients entered into the Optic Neuritis Treatment Trial. Prospective multicenter clinical trial. Referral centers. Brain magnetic resonance images from 418 patients with acute optic neuritis (77% women; mean age, 32.0 years) were evaluated at a central reading center with the use of a standardized classification system (ranging from 0 for normal to IV for most extensive changes). Of the scans, 40.9% were classified as grade 0, 10.8% as grade I, 9.1% as grade II, 6.7% as grade III, and 32.5% as grade IV. For patients with isolated (monosymptomatic) optic neuritis, 26.7% had two or more lesions. We found a lower prevalence of brain magnetic resonance imaging abnormalities in isolated optic neuritis than previous studies have reported. This likely is due to our study having a higher degree of standardization of patient inclusion criteria, which limited patient selection bias.


Insect microRNAs: Structure, function and evolution.
The small regulatory non-coding RNA molecules, known as microRNAs, have been recognized as potential regulator(s) of gene expression at the post-transcriptional level. In Drosophila melanogaster, microRNAs have been identified that control important developmental processes such as apoptosis, cell division, Notch signaling, neural development and oogenesis, among others. Once activated through a step-wise maturation process, a microRNA can potentially regulate more than 50 target genes temporally and spatially in Drosophila. Thus, it is of tremendous importance to understand how these small RNA molecules have evolved and how they are expressed and regulated to impact cellular function and the associated evolutionary fitness. Studies of microRNAs in diverse insect species using the genome sequences (at least 49 insect genome sequences are in progress) may provide important clues to better understand the natural selection of microRNA genes in particular and their impact on biological functions in insects in general.


[HLA-linked susceptibility to intractable vasculitis syndrome].
Sixty-four patients with Takayasu arteritis, 204 patients with rheumatoid arthritis (RA), 53 patients with systemic lupus erythematosus (SLE) and 64 patients with mixed connective tissue disease (MCTD) in the Japanese population were typed for HLA class II genes at DNA level. The results suggest that susceptibility to Takayasu arteritis is controlled by HLA-B52-DRB1*1502-DRB5*0102-DQA1*0103-DQB1 *0601-DPA1*02-DPB1*0401 haplotype, because the frequency of that HLA haplotype was increased with statistical significance in the patients as compared with that in the healthy controls. On the other hand, the HLA-DRB1*0405-DQA1*0301-DQB1*0401 haplotype was associated with the susceptibility to RA. Susceptibility to SLE and MCTD are controlled by the HLA-DRB1 *1501-DRB5*0101-DQA1*0102-DQB1*0602 haplotype and the HLA-DRB1*0401-DRB4*0101- DQA1*0301-DQB1*0301, haplotype respectively. These observations clearly indicate the presence of HLA-linked disease susceptibility genes to Takayasu arteritis, RA, SLE and MCTD, and the difference in HLA-linked genetic background between these four diseases.


Comparison of systemic stress responses between percutaneous nephrolithotomy (PCNL) and open nephrolithotomy.
Stimulation of patient's immune response and therefore increasing inflammatory indices in patients who underwent invasive treatment methods for kidney stone removing can be predictable. In the present study, we tried to evaluate the differences of inflammatory indices in percutaneous nephrolithotomy (PCNL) and compared them with open stone surgery in patients with kidney stones. In a clinical trial study, 15 adult patients that scheduled to undergo PCNL and 15 patients who were candidate for open stone surgery matched for sex and age were included. Body temperature and concentrations of white blood cell, hemoglobin, C-reactive protein, interleukin-6, 24-hour urine cortisol levels, fibrinogen, TNF-alpha, and total antioxidant status (TAS) were measured. Pain severity was also measured on the basis of verbal rating scale (VRS). All measurements were recorded immediately before and 24 hours after operation. Patients that underwent open surgery had more severe pain than PCNL group (P = 0.001). Postoperative fever in the first group was more prevalent than other group (P = 0.020). Also, surgery time (P < 0.001), and total length of stay in hospital (P < 0.001) were higher in open surgery group. Differences rate of white blood cell (P = 0.003), C-reactive protein (P = 0.005), 24-hour urine cortisol level at 24 and 48 hours after open surgery were significantly more than PCNL (P = 0.02, P = 0.048, respectively). According to the higher postoperative complications and patient's inflammatory response in open stone surgery in comparison with PCNL, stone removing by PCNL has lower impact in terms of stress response in comparison to open surgery to the treatment of kidney stones.


A novel triterpene from Ceriops tagal.
A novel lupane derivative 3beta-(E)-feruloyllupeol has been isolated from the embryo of Ceriops tagal. The structure of the new triterpene was determined on the basis of spectral and chemical studies.


Exogenous melatonin induces drought stress tolerance by promoting plant growth and antioxidant defence system of soybean plants.
Melatonin is an indolamine bioactive molecule that regulates a wide range of physiological processes during plant growth and enhances abiotic stress tolerance. Here we examined the putative role of exogenous melatonin application (foliar or root zone) in improving drought stress tolerance in soybean seedlings. Pre-treatment of soybean seedlings with melatonin (50 and 100 µM) was found to significantly mitigate the negative effects of drought stress on plant growth-related parameters and chlorophyll content. The beneficial impacts against drought were more pronounced by melatonin application in the rhizosphere than in foliar treatments. The melatonin-induced enhanced tolerance could be attributed to improved photosynthetic activity, reduction of abscisic acid and drought-induced oxidative damage by lowering the accumulation of reactive oxygen species and malondialdehyde. Interestingly, the contents of jasmonic acid and salicylic acid were significantly higher following melatonin treatment in the root zone than in foliar treatment compared with the control. The activity of major antioxidant enzymes such as superoxide dismutase, catalase, polyphenol oxidase, peroxidase and ascorbate peroxidase was stimulated by melatonin application. In addition, melatonin counteracted the drought-induced increase in proline and sugar content. These findings revealed that modifying the endogenous plant hormone content and antioxidant enzymes by melatonin application improved drought tolerance in soybean seedlings. Our findings provide evidence for the stronger physiological role of melatonin in the root zone than in leaves, which may be useful in the large-scale field level application during drought.


Symmetrical upper limb peromelia and lower limb phocomelia associated with a de novo apparently balanced reciprocal translocation: 46,XX,t(2; 12)(p25.1;q24.1).
We report a female fetus of 20 weeks gestation with severe symmetrical deformity affecting all four limbs. These deformities were unusual in that there was upper limb peromelia and lower limb phocomelia. No additional major malformations were identified on postmortem examination. In particular there was no evidence of splenogonadal fusion or micrognathia and hypoglossia. The limb malformations in this case are associated with a de novo apparently balanced reciprocal translocation 46,XX,t(2;12)(p25.1;q24.1). The cytogenetic features of Roberts-SC phocomelia syndrome were not detected. Unfortunately, the fibroblast line died and no FISH or DNA analysis could be carried out. In spite of this, the case is presented as it may be useful to other researchers in the selection of candidate genes for mendelian forms of peromelia and phocomelia.


Antacids revisited: review on contemporary facts and relevance for self-management.
Heartburn and acid regurgitation are the typical symptoms of gastroesophageal reflux. Despite the availability of several treatment options, antacids remain the mainstay treatment for gastroesophageal reflux-related symptoms based on their efficacy, safety, and over-the-counter availability. Antacids are generally recommended for adults and children at least 12 years old, and the FDA recommends antacids as the first-line treatment for heartburn in pregnancy. This narrative review summarizes the mechanism, features, and limitations related to different antacid ingredients and techniques available to study the acid neutralization and buffering capacity of antacid formulations. Using supporting clinical evidence for different antacid ingredients, it also discusses the importance of antacids as OTC medicines and first-line therapies for heartburn, particularly in the era of the COVID-19 pandemic, in which reliance on self-care has increased. The review will also assist pharmacists and other healthcare professionals in helping individuals with heartburn to make informed self-care decisions and educating them to ensure that antacids are used in an optimal, safe, and effective manner.


Determination of the chemical shielding tensor orientation from two or one of the three conventional rotations of a single crystal.
Chemical shift anisotropy (CSA) is an immensely useful interaction to study the structure, dynamics, and function of a wide variety of chemical and biological molecules. Traditionally the only unambiguous way to determine both the principal values and the orientation of the principal axes of the CSA tensor has been to follow the chemical shift frequency changes as a crystal of known structure is rotated relative to the direction of the external magnetic field. This classic method employs rotations about three mutually orthogonal axes of a single crystal. It is shown here that just two, or one, of the above rotations suffice to determine the CSA tensor orientation by borrowing, the easy to obtain, principal values of CSA from an independent source. Methods for using two rotation patterns or even a single rotation pattern are described and illustrated with known chemical shielding tensors.


SACRAL syndrome: spinal dysraphism, anogenital, cutaneous, renal and urologic anomalies, associated with an angioma of lumbosacral localization.
Publications concerning perineal infantile hemangiomas are scarce, and comprise no large series. Studying clinical features of hemangiomas of the perineal area, complications and associated malformations. Retrospective analysis of all hemangiomas localized in the perineal area, encountered at the Children's Hospital in Bordeaux from 1994. Of 49 perineal hemangiomas (34 girls, 15 boys), 5 patients had accompanying malformation, mainly lipomyelomeningocele with tethered cord. The superficial hemangiomas were more represented in males and presented sooner than the nodular counterpart. The average rate of ulceration was 73%, ulcerations developed earlier in the superficial forms than their nodular counterparts (2 vs. 4 months). Superficial perineal hemangiomas are more often complicated by ulceration, and are associated with developmental anomalies. As a counterpart for the PHACE syndrome in facial hemangioma, we propose the acronym SACRAL for perineal hemangiomas: Spinal dysraphism, Anogenital anomalies, Cutaneous anomalies, Renal and urologic anomalies, associated with Angioma of Lumbosacral localization.


Colchicine concentration in leukocytes of patients with familial Mediterranean fever.
Free and total plasma, granulocyte and mononuclear cell colchicine concentrations were measured by radioimmunoassay in 30 patients with familial Mediterranean fever treated with colchicine 0.5 to 2 mg day-1. Colchicine concentrations showed a large intersubject variability in plasma (0.13-1.75 ng ml-1), granulocytes (4 to 64 ng/10(9) cells), and mononuclear cells (11.4 to 57.6 ng/10(9) cells). Whereas unbound and total plasma colchicine concentrations were well correlated, no correlation was found between total or free plasma and granulocyte or mononuclear cell colchicine concentrations and dose of administered colchicine. In contrast, total or free plasma and granulocyte or mononuclear cell colchicine concentrations were correlated using a hyperbolic function indicating saturable colchicine distribution in both leukocyte populations.


[Psychoanalysis between archeology and history].
Using the Freudian metaphor of psychoanalysis as archeology, we can identify several "archeologies" in the past of psychoanalysis: in the activities of non-analysts who, as practitioners, dug into the past of Freud, and of analysts who, as laboratory scientists, limited themselves to assembling concepts. We then compared these heterogeneous archeologies, be they scholarly, commonplace, or even scandalous, to the practice of the history of psychoanalysis initiated by Freud and continued by his disciples. The hagiography and more generally, the secrecy that surrounded certain parts of Freud's life and certain of his theories were demolished by the arrival of non-analyst historians, little concerned with preserving the aims that psychoanalysis, for self-preserving reasons, kept alive despite its ideal of a lack of purpose. The analysts, mediocre archeologists in the field, were compensated by their science of assembling piecemeal ideas. On the other hand, in the role of historian, of those who recount, the analysts were not well served by their techniques, coming as they did from the field of psychoanalysis. Thanks to this four-way comparison, archaeologist analysts, non-analyst archaeologists, analyst historians, and non-analyst historians, we can attempt to sketch several conclusions for a methodology of the psychoanalytical history of psychoanalysis.


Fibre types, enzyme activities and substrate utilisation in skeletal muscles of horses competing in endurance rides.
Venous blood samples and middle gluteal muscle biopsies were obtained from 21 horses taking part in 100 km or 50 km endurance rides. Group A consisted of seven horses competing over 100 km (four horses completed the ride). Group B consisted of the six horses that were among the 10 best over 50 km while the other eight horses of Group C completed 50 km at a slower speed. Blood lactate, glycerol and creatine kinase increased in all groups while aspartate aminotransferase levels were higher only in Group A. No changes was found in blood glucose in Groups B and C while horses in Group A had lower levels after the ride. Neither fibre composition, fibre areas nor enzyme activities differed between the groups. Intramuscular glycogen content was similar before the ride in all groups. After the ride glycogen had decreased only half as much in Group C as compared to Groups A and B. Group C had a higher intramuscular triglyceride content at rest than Group B. The greatest decrease in triglyceride content after the ride was found in Group C. In Group A and B many Type I, IIA and IIB fibres were glycogen depleted after the ride while in Group C mainly Type I and some Type IIA fibres were depleted. The results of this study show that intramuscular carbohydrate and lipid stores are both important fuels during endurance rides.


3800 Years of quantitative precipitation reconstruction from the Northwest Yucatan Peninsula.
Precipitation over the last 3800 years has been reconstructed using modern pollen calibration and precipitation data. A transfer function was then performed via the linear method of partial least squares. By calculating precipitation anomalies, it is estimated that precipitation deficits were greater than surpluses, reaching 21% and <9%, respectively. The period from 50 BC to 800 AD was the driest of the record. The drought related to the abandonment of the Maya Preclassic period featured a 21% reduction in precipitation, while the drought of the Maya collapse (800 to 860 AD) featured a reduction of 18%. The Medieval Climatic Anomaly was a period of positive phases (3.8-7.6%). The Little Ice Age was a period of climatic variability, with reductions in precipitation but without deficits.


An investigation of the effect of folic acid and its delivery routes on broiler chickens' hatch and growth performance, blood biochemistry, anti-oxidant status, and intestinal morphology.
This study investigated the effect of folic acid (FA) and its delivery routes (in-feed or in ovo) on broiler chicken's hatch and growth performance, blood biochemistry, anti-oxidant status, and intestinal morphology. A total of 1,860 Cobb 500 hatching eggs were incubated for 21 d. On day 12 of incubation, viable eggs were randomly allotted to four groups: the noninjected group, in ovo saline (injected with 0.1 mL/egg of saline solution), in ovo FA 1 (injected with 0.1 ml FA containing 0.1 mg/egg; FA1), and in ovo FA 2 (injected with 0.1 ml FA containing 0.15 mg/egg). All in ovo treatments were delivered via the amnion. At hatch, chicks were re-allotted to five new treatment groups: FA1, FA2, in-feed FA (FA 3; 5mg/kg in feed), in-feed bacitracin methylene disalicylate (BMD; 55 mg/kg in feed), and negative control (NC; corn-wheat-soybean diet) in 6 replicate pens (22 birds/pen) and raised in starter (days 0 to14), grower (days 15 to 24), and finisher (days 25 to 35) phases. Hatch parameters were assessed on day 0, and body weight and feed intake (FI) were determined weekly. On day 25, 1 bird/cage was euthanized, immune organs weighed, and intestinal tissues harvested. Blood samples were collected for biochemistry and anti-oxidant (Superoxide dismutase-SOD and Malondialdehyde-MDA) analysis. Data were analyzed in a randomized complete block design. While FA1 and FA2 decreased (P < 0.001) hatchability in a dose-dependent manner, FA2 caused a 2% increase (P < 0.05) in average chick weight compared to the noninjected group. Compared to the BMD treatment, FA3 decreased (P < 0.05) average FI across all feeding phases. At the end of the trial on day 35, FA2 had similar feed conversion ratio as the BMD treatment while recording less (P < 0.001) FI. FA1 and FA2 recorded a tendency (P < 0.1) to increase MDA levels and SOD activity by 50% and 19%, respectively, compared to the NC treatment. Compared to NC treatment, FA2 increased (P < 0.01) villus height, width, and villus height to crypt depth ratio in the duodenum, and villus width in the jejunum. Besides its negative effect on hatchability, FA2 may help improve embryonic development and anti-oxidant status in broiler chickens.


Seizures associated with recreational drug abuse.
We retrospectively identified 49 cases of recreational drug-induced seizures in 47 patients seen at the San Francisco General Hospital between 1975 and 1987. Most patients experienced a single generalized tonic-clonic seizure associated with acute drug intoxication, but 7 patients had multiple seizures and 2 patients developed status epilepticus. The recreational drugs implicated were cocaine (32 cases), amphetamine (11), heroin (7), and phencyclidine (4). A combination of drugs was responsible in 11 cases. Seizures occurred independent of the route of administration, and occurred in both first-time and chronic abusers. Ten patients (21%) reported having had prior seizures, all with a close temporal association with drug abuse. Other than 1 patient who developed prolonged status epilepticus that caused a fixed neurologic deficit, most patients had no obvious short-term neurologic sequelae.


Uncertainty analysis of field placement error measurements using digital portal and simulation image correlations.
An uncertainty analysis of a field placement error measurement method using correlations between digital portal and simulation images has been performed. This analysis used the Monte Carlo method to simulate random uncertainties arising in image registration and portal field edge detection. The uncertainty analysis used data from a field placement error study to predict the dependences of the measurement method upon image matchpoint number and spatial distribution, image registration, and uncertainties arising in the detection and description of the field edge in a portal image. It was shown that the uncertainty in the field registration had the most significant effect upon the measurement uncertainty, whereas the number of matchpoints had an extremely limited effect (beyond the minimum required for the mathematical procedure used in registration). In contrast, it was shown that an accurate field placement error measurement required that the number of pixels describing a field edge used for comparisons should exceed 20, thus automatically setting a minimum field length necessary for field placement comparisons. It was also shown that the spatial uniformity of the matchpoints in an image pair had a limited effect upon the field placement error measurement, provided that the points are distributed over about 15% of the image area.


Magnetic resonance imaging of spin-polarization transfer of polarized Xe atoms dissolving into ethanol.
We detect the free-induction signals of xenon atoms polarized by spin-exchange optical pumping. The temperature dependence of dissolution and spin-polarization transfer of xenon atoms to ethanol is measured by simultaneous detection of both xenon and proton signals. The polarization of proton is efficiently enhanced in the xenon-saturated solution at low magnetic fields. The large polarization and chemical shift enable us to obtain clearly the distribution image of xenon atoms near the gas-liquid and liquid-liquid boundaries. Therefore the localization of polarized xenon atoms is observed near the surface. By time-resolved magnetic resonance imaging of polarized xenon and polarization-enhanced proton, the spin dynamics is qualitatively studied for the nuclear spins interacting with each other in a dense solution.


A case of mediastinal seminoma presenting as superior vena cava syndrome.
Primary mediastinal seminoma is a rare tumor usually with nonspecific symptoms such as chest pain, dyspnea and hoarseness, but superior vena cava syndrome (SVCS) is an extremely uncommon syndrome. We report a 25-year-old man who presented with superior vena cava syndrome for 1 month and a 1-week history of retrosternal chest pain. Thorax computerized tomography demonstrated a soft tissue mass in the anterior mediastinum with stippled calcifications compressing the superior vena cava and other major vessels. Transthoracic biopsy showed primary seminoma of the anterior mediastinum. Combined chemoradiotherapy was performed and the patient was considered to have a partial response to treatment.


Leptospirosis: a report on a series of five autochthonous cases in a Greek region.
Leptospirosis is a worldwide zoonotic disease difficult to diagnose both to the clinic and the laboratory. Many risk factors have been involved, such as planting, hunting, harvesting and butchering or sports, such as rafting. We reported our experience through a period of 20 months and we tried to investigate prognostic factors predicting clinical outcomes. Five male patients were admitted to our Department with a median age of 40 years. Overall, three out of five patients presented to other hospital and were transferred to ours with a wrong or delayed diagnosis. In terms of clinical signs and symptoms, all presented with fever, myalgia, headache and jaundice, whereas conjunctival suffusion was present in 80% of them. Acute renal injury and liver deficiency were diagnosed in all subjects. Acute renal failure management required dialysis in 3/5 patients, whereas renal recovery was achieved soon after clinical improvement. However, clinical awareness and serology are the most important tools for accurate and quick diagnosis in order to administer the appropriate therapy.


Genetic analysis of a human rotavirus that belongs to subgroup I but has an RNA pattern typical of subgroup II human rotaviruses.
We have previously found (O. Nakagomi, T. Nakagomi, H. Oyamada, and T. Suto, J. Med. Virol. 17:29-34, 1985), during an epidemiological study in Japan, a novel human rotavirus that belongs to subgroup I but has a long RNA pattern typical of subgroup II human rotaviruses. From the stool specimen containing this virus, we successfully isolated in MA104 cells a rotavirus, designated AU-1, which possesses these novel characteristics. The possibility that strain AU-1 was a laboratory contaminant of an animal rotavirus previously adapted to tissue culture cells was ruled out, and the identity of the AU-1 strain was established. Genetic analysis by RNA-RNA hybridization revealed that the AU-1 strain is not a simple reassortant between subgroup I and II human rotaviruses but that it shares a high level of sequence homology only with the gene encoding VP7 (the major neutralization protein) of serotype 3 human rotaviruses. Weak homology of the genomic RNA segments was also observed between the AU-1 strain and animal rotavirus strains, including rhesus rotavirus strain RRV and bovine rotavirus strain NCDV. These results suggest that the AU-1 strain may be an animal rotavirus that infected a human.


Learning and Developing Together for Improving the Quality of Care in a Nursing Home, Is Appreciative Inquiry the Key?
To investigate the impact of Appreciative Inquiry (AI) on learning and developing together for improving the quality of care in a nursing home, and to explore experiences following the four phases of the AI cycle, an AI was performed as part of participative action research. Interviews, group discussions, creative methods of storytelling, and reflections were used in the AI sessions. Staff members were interviewed to evaluate the AI process. All of the interviews were recorded and transcribed. Data were analyzed thematically using Maxqda and were discussed by the interviewers until consensus was reached. The sessions resulted in ten action proposals to improve healthcare. One proposal was worked out in agreements on cooperation. The evaluation revealed that the sessions have given a boost to the team spirit, and involvement at the location leading to more cooperation and communication during the shifts. The evaluation indicated that it is important to convert the action plans of the sessions into actions, which are then evaluated. AI was advised as a way of learning where everyone is involved, and mutual agreements are made. This study has shown that AI can be a valuable way to support learning and development to promote the quality of care in a nursing home.


Subtotal hepatectomy and whole graft auxiliary transplantation for acetaminophen-associated acute liver failure.
An acetominophen overdose (AOD) is the leading cause of acute liver failure (ALF) in the UK and USA. For patients who meet the King's College Hospital criteria, (mortality risk > 85%), an emergency orthotopic liver transplantation (OLT) is conventionally performed with subsequent life-long immunosuppression. A new technique was developed in 1998 for AOD-induced ALF where a subtotal hepatectomy (right hepatic trisectionectomy) and whole graft auxiliary liver transplant (WGALT) was performed with complete withdrawal of immunosupression during the first year post-operatively. During 1998-2010, 68 patients were listed for an emergency transplantation for AOD ALF at our institution: 28 died waiting, 16 underwent OLT and 24 a subtotal hepatectomy with WGALT. Eight OLT (50%) and 16 WGALT remain alive (67%); actuarial survival at 5 years OLT 50%, WGALT 63%, P = 0.37. All patients who had successful WGALT are off immunosuppression. Poor prognostic factors in the WGALT group included higher donor age (40.4 versus 53.9, P = 0.043), requirements for a blood transfusion (4.3 versus 7.6, P = 0.0043) and recipient weight (63.1 versus 54 kg, P = 0.036). Although OLT remains standard practice for AOD-induced ALF, life-long immunosuppression is required. A favourable survival rate using a subtotal hepatectomy and WGALT has been demonstrated, and importantly, all successful patients have undergone complete immunosuppression withdrawal. This technique is advocated for patients who have acetominophen hepatotoxicity requiring liver transplantation.


Infradian rhythms of alanine aminopeptidase excretion during gentamicin therapy.
Urinary excretion of alanine aminopeptidase (EC 22.214.171.124) was examined in 30 patients (22 women, 8 men, range 38-81 years; mean age 55.4) receiving gentamicin in a therapeutic dosage, which was based on the monitored blood creatinine concentration. In general, therapy lasted 10 days. The excretion of 24 individuals displayed significant infradian rhythms with periods between 2.2 and 8.1 days. In 10 of these 24 patients (42%) a circaseptan period was detected. The high portion of circaseptan rhythms might have been induced by the detrimental effects of gentamicin on the proximal tubule and the resulting processes of reconstitution.


HeH+ Collisions with H2: Rotationally Inelastic Cross Sections and Rate Coefficients from Quantum Dynamics at Interstellar Temperatures.
We report for the first time an accurate ab initio potential energy surface for the HeH+-H2 system in four dimensions (4D) treating both diatomic species as rigid rotors. The computed ab initio potential energy point values are fitted using an artificial neural network method and used in quantum close coupling calculations for different initial states of both rotors, in their ground electronic states, over a range of collision energies. The state-to-state cross section results are used to compute the rate coefficients over a range of temperatures relevant to interstellar conditions. By comparing the four dimensional quantum results with those obtained by a reduced-dimensions approach that treats the H2 molecule as an averaged, nonrotating target, it is shown that the reduced dimensionality results are in good accord with the four dimensional results as long as the HeH+ molecule is not initially rotationally excited. By further comparing the present rate coefficients with those for HeH+-H and for HeH+-He, we demonstrate that H2 molecules are the most effective collision partners in inducing rotational excitation in HeH+ cation at interstellar temperatures. The rotationally inelastic rates involving o-H2 and p-H2 excitations are also obtained and they turn out to be, as in previous systems, orders of magnitude smaller than those involving the cation. The results for the H2 molecular partner clearly indicate its large energy-transfer efficiency to the HeH+ system, thereby confirming its expected importance within the kinetics networks involving HeH+ in interstellar environments.


Environmental surveillance of antimicrobial resistance (AMR), perspectives from a national environmental regulator in 2023.
The development, and in some cases increasing prevalence, of resistance to antimicrobials used in clinical and veterinary settings has long been recognised. In recent years, the concept of 'One Health' has added recognition of the role that the environment plays in health protection along with the need for protection of the health of the environment itself. Organisations including the World Health Organization, United Nations Environment Programme, and national governments have identified a need for surveillance of antimicrobial resistance in the environment to sit alongside the surveillance carried out in clinical, veterinary and food sectors. However, having recognised the need for environmental surveillance there are multiple challenges in deciding what this should entail. For example, what pathogens or genes to monitor, who or what we wish to protect and what measures we wish to enable to decrease infection risks. That might include sampling near a source of resistant organisms entering the environment or conversely sampling where the exposure actually occurs. Choices need to be made at both policy and technical levels based on the detailed purposes of surveillance. This paper discusses these issues from the perspective of a national environmental regulator.


Interleukin-18 levels on admission are associated with mid-term adverse clinical events in patients with ST-segment elevation acute myocardial infarction undergoing percutaneous coronary intervention.
The long-term prognostic value of interleukin (IL)-18 in patients with ST-segment elevation acute myocardial infarction (STEMI) has been conflicting. Thus, the purpose of this study was to test whether the level of interleukin-18 measured on admission can predict long-term adverse clinical events in patients with STEMI who were undergoing percutaneous coronary intervention (PCI). We recruited 288 consecutive STEMI patients (210 men, average age [71.42 +/- 10.32] years) with onset < 6 hours who were undergoing primary PCI, and 148 age- and gender-matched control subjects. Plasma levels of IL-18 were measured by enzyme-linked immunosorbent assay (ELISA) in all subjects. The patients with STEMI were then followed prospectively over 434 days (range, 0 to 642 days) for the occurrence of composite major adverse clinical events (MACE) (cardiac mortality, recurrent myocardial infarction, or readmission due to advanced heart failure). Patients with STEMI exhibited higher levels of plasma IL-18 (P < 0.001) compared with the control subjects. Positive correlations between IL-18 and cardiac troponin-I (cTnI) (r = 0.353, P = 0.0004) and IL-18 and high-sensitivity C-reactive protein (hs-CRP) (r = 0.420, P < 0.001) were observed by Spearman's correlations analysis. Logistic regression analysis demonstrated that IL-18 >/= 450 pg/mL (OR 10.854, 95% CI 2.328 to 50.594, P < 0.0001) was a significant independent predictor of composite MACE at 60 days. Cox regression analysis demonstrated that high plasma IL-18 levels were not correlated with the occurrence of long-term composite MACE. The level of plasma IL-18 on admission may predict 60-day adverse clinical outcome, but not the long-term adverse clinical events in patients with STEMI undergoing PCI, and may be useful for mid-term risk stratification.


Cation-induced aggregation of cat Tamm-Horsfall glycoprotein and its possible role in feline urolithiasis.
The in vitro cation-induced aggregation properties of cat Tamm-Horsfall protein (cTHP), a urinary glycoprotein, were examined and related to the potential role of cTHP in feline urolithiasis. The aggregation assay involved adding either CaCl2, MgCl2, or NaCl to solutions containing purified cTHP, and then separating the aggregated cTHP by centrifugation. The concentration of cTHP remaining in the supernatant was quantified using a previously developed enzyme-linked immunosorbent assay (ELISA). The effect that buffer pH, cTHP concentration, and urea concentration had on cTHP aggregation also were examined. Of the three salts, CaCl2 consistently was most efficient at precipitating cTHP, while MgCl2 was slightly less efficient. At least ten times more NaCl than CaCl2 or MgCl2 was required for comparable cTHP aggregation. As the pH decreased, increasing concentrations of the salts were required to aggregate cTHP. Increased amounts of CaCl2 and MgCl2 also were required to aggregate cTHP when the urea concentration was increased. As cTHP concentration increased within the physiological range, lower concentrations of CaCl2 and MgCl2 were required to precipitate 50% of the cTHP. Several aspects of the in vitro aggregation properties of cTHP correlate closely with previously identified risk factors for feline urolithiasis, strengthening the theory that cTHP aggregation may be important in this disease.


Liver metabolism of porphyrins and haem.
The liver is an active site for the biosynthesis of haem and porphyrinogens/porphyrins, which are intermediates of the haem biosynthetic pathway, because haem is required for functional activity of the cytochrome P 450 system and other critical hepatic haemoproteins. The production of hepatic haem is regulated primarily through the activity of aminolaevulinic acid synthase which is the first and normally rate-limiting enzyme of the pathway. This is, in turn, controlled by a putative regulatory haem pool. Hepatic haem can be repleted by the intravenous administration of haem, which is the basis for haem therapy in patients with acute porphyric attacks. The liver catabolizes haem to bilirubin through microsomal haem oxygenase activity and excretes haem into bile along with porphyrins. Biliary excretion of porphyrins increases significantly in patients with some types of porphyria. In protoporphyria this may cause liver damage as a result of protoporphyrin toxicity. The delineation of the pathway for protoporphyrin excretion into bile should facilitate therapy in protoporphyria by identifying ways in which protoporphyrin excretion can be enhanced.


NFATc3 regulates BK channel function in murine urinary bladder smooth muscle.
The nuclear factor of activated T-cells (NFAT) is a Ca(2+)-dependent transcription factor that has been reported to regulate the expression of smooth muscle contractile proteins and ion channels. Here we report that large conductance Ca(2+)-sensitive potassium (BK) channels and voltage-gated K(+) (K(V)) channels may be regulatory targets of NFATc3 in urinary bladder smooth muscle (UBSM). UBSM myocytes from NFATc3-null mice displayed a reduction in iberiotoxin (IBTX)-sensitive BK currents, a decrease in mRNA for the pore-forming alpha-subunit of the BK channel, and a reduction in BK channel density compared with myocytes from wild-type mice. Tetraethylammonium chloride-sensitive K(V) currents were elevated in UBSM myocytes from NFATc3-null mice, as was mRNA for the Shab family member K(V)2.1. Despite K(V) current upregulation, bladder strips from NFATc3-null mice displayed an elevated contractile response to electrical field stimulation relative to strips from wild-type mice, but this difference was abrogated in the presence of the BK channel blocker IBTX. These results support a role for the transcription factor NFATc3 in regulating UBSM contractility, primarily through an NFATc3-dependent increase in BK channel activity.


Metadynamics as a tool for mapping the conformational and free-energy space of peptides--the alanine dipeptide case study.
There is a need for a fast, accurate, and reliable method of sampling the conformational space of peptides and proteins in order to obtain a balanced free-energy profile which can lead to our understanding of protein structure. We have utilized metadynamics for the conformational study of the solvated alanine dipeptide molecule, and our results show that the method has proven to be competent as a fast, robust, and reliable method for the conformation free-energy calculations of peptides in an explicit solvent, surpassing traditional methods such as umbrella sampling. We have also addressed the issue of the influence of different water models on the resulting free-energy profile in order to consistently decompose the setting of our simulation. All of the explicit water models for the simulation of biomolecules TIP3P, TIP4P, TIP4P/Ew, TIP5P, and SPCE have exhibited similar effects on the conformational preferences of alanine dipeptide with no significant differences. On the other hand, by comparing the potential energy surface in the gas phase and the free-energy surface in a water environment, we have shown that the interaction with water molecules is one of the most important structure-driving elements, with a great influence on the free-energy surface (FES) of the solvated peptide and the conformational preferences of the peptide backbone. All of the tested force fields (ff03, ff99SB, opls-aa, and charmm27) appreciably differ in the population of the individual conformers and the barriers between them. Significant divergence was found on both the potential energy surface (PES) as well as free-energy surface (FES) calculated by charmm27. We have therefore concluded that the differences originate dominantly from the parametrization of the peptide backbone in the given force field rather than from a noncovalent interaction with water molecules.


Salt Stress-Induced Loss of Iron Oxidoreduction Activities and Reacquisition of That Phenotype Depend on rus Operon Transcription in Acidithiobacillus ferridurans.
The type strain of the mineral-oxidizing acidophilic bacterium Acidithiobacillus ferridurans was grown in liquid medium containing elevated concentrations of sodium chloride with hydrogen as electron donor. While it became more tolerant to chloride, after about 1 year, the salt-stressed acidophile was found to have lost its ability to oxidize iron, though not sulfur or hydrogen. Detailed molecular examination revealed that this was due to an insertion sequence, ISAfd1, which belongs to the ISPepr1 subgroup of the IS4 family, having been inserted downstream of the two promoters PI and PII of the rus operon (which codes for the iron oxidation pathway in this acidophile), thereby preventing its transcription. The ability to oxidize iron was regained on protracted incubation of the culture inoculated onto salt-free solid medium containing ferrous iron and incubated under hydrogen. Two revertant strains were obtained. In one, the insertion sequence ISAfd1 had been excised, leaving an 11-bp signature, while in the other an ∼2,500-bp insertion sequence (belonging to the IS66 family) was detected in the downstream inverted repeat of ISAfd1 The transcriptional start site of the rus operon in the second revertant strain was downstream of the two ISs, due to the creation of a new "hybrid" promoter. The loss and subsequent regaining of the ability of A. ferriduransT to reduce ferric iron were concurrent with those observed for ferrous iron oxidation, suggesting that these two traits are closely linked in this acidophile.IMPORTANCE Iron-oxidizing acidophilic bacteria have primary roles in the oxidative dissolution of sulfide minerals, a process that underpins commercial mineral-processing biotechnologies ("biomining"). Most of these prokaryotes have relatively low tolerance to chloride, which limits their activities when only saline or brackish waters are available. The study showed that it was possible to adapt a typical iron-oxidizing acidophile to grow in the presence of salt concentrations similar to those in seawater, but in so doing they lost their ability to oxidize iron, though not sulfur or hydrogen. The bacterium regained its capacity for oxidizing iron when the salt stress was removed but simultaneously reverted to tolerating lower concentrations of salt. These results suggest that the bacteria that have the main roles in biomining operations could survive but become ineffective in cases where saline or brackish waters are used for irrigation.


Impact of Post-Translational Modifications of Crop Proteins under Abiotic Stress.
The efficiency of stress-induced adaptive responses of plants depends on intricate coordination of multiple signal transduction pathways that act coordinately or, in some cases, antagonistically. Protein post-translational modifications (PTMs) can regulate protein activity and localization as well as protein-protein interactions in numerous cellular processes, thus leading to elaborate regulation of plant responses to various external stimuli. Understanding responses of crop plants under field conditions is crucial to design novel stress-tolerant cultivars that maintain robust homeostasis even under extreme conditions. In this review, proteomic studies of PTMs in crops are summarized. Although the research on the roles of crop PTMs in regulating stress response mechanisms is still in its early stage, several novel insights have been retrieved so far. This review covers techniques for detection of PTMs in plants, representative PTMs in plants under abiotic stress, and how PTMs control functions of representative proteins. In addition, because PTMs under abiotic stresses are well described in soybeans under submergence, recent findings in PTMs of soybean proteins under flooding stress are introduced. This review provides information on advances in PTM study in relation to plant adaptations to abiotic stresses, underlining the importance of PTM study to ensure adequate agricultural production in the future.


The care of necrotizing soft-tissue infections: patterns of definitive intervention at a large referral center.
The objective of this study was 1) to assess the methods employed in treating necrotizing soft-tissue infections (NSTIs) by an experienced referral center; 2) to characterize the patient population who is at risk for the development of NSTI and determine predictors of mortality within this population; and 3) to compare outcomes between those who are transferred to a burn center after diagnosis and those who present directly to such a center. A retrospective chart review was performed on 81 patients during a 6-year period who were admitted to our institution with a diagnosis of NSTI. Once admitted, variables associated with surgical and medical management were collected, and patient outcomes were recorded. All variables were analyzed for their prognostic value. Multiple comorbidities were common, with obesity being the most common preexisting condition. Acute kidney injury and multiple organ failure on admission were found to be predictive for increased mortality (P < .01). Patients who presented directly to our institution were quicker to grafting (P = .04) and underwent fewer total operations (P = .05) than transferred patients. Overall mortality was 20% and was comparable across direct admits vs transfers, and over time. NSTI remains a significant source of morbidity and mortality, especially in obese patients and those with significant comorbidities. Treatment at a burn center may reduce morbidity; however, associated mortality remains constant. Similarly, while hospital course and morbidity at our institution may be improved from years past, mortality has remained consistent over time.