Determination of aflatoxins, ochratoxin a, and zearalenone in mixed feeds, with detection by thin layer chromatography or high performance liquid chromatography.
A sensitive, reliable, and economical method for the determination of 6 mycotoxins in mixed feeds is described. The feed is extracted with chloroform-water and the extract is cleaned up by using a disposable Sep-Pak silica cartridge. The procedure requires less time (15 min from sample extraction to extract preparation) and less solvent (approximately one-tenth) compared with conventional methods and is suitable for a fast, economical screen. Additional cleanup procedures, involving dialysis or extraction into base, are described for samples containing high levels of interfering compounds. Thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) with fluorescence detection are described for identification and estimation of mycotoxins. The method has been applied to a wide range of mixed feeds, including laboratory animal diets, and raw materials. The limit of detection is 1 microgram/kg for all mycotoxins measured by HPLC.


Composite Biopolymer-Based Wafer Dressings Loaded with Microbial Biosurfactants for Potential Application in Chronic Wounds.
In this study two bioactive polysaccharide polymers kappa-carrageenan (CARR) and sodium alginate (SA) incorporated with microbial biosurfactants (BSs) were formulated as medicated wafer dressings for potential application in chronic wounds. Wafers were loaded with BSs at concentrations of 0.1% and 0.2% rhamnolipids (RL) and 0.1% and 5% sophorolipids (SL) and were functionally characterized using scanning electron microscopy (SEM), texture analysis (mechanical strength and in vitro wound adhesion), attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray diffraction (XRD) and exudate handling properties (pore analysis, swelling index, water absorption (Aw), equilibrium water content (EWC), evaporative water loss (EWL) and water vapor transmission rate (WVTR). The wafers were tactile and ductile in appearance with a hardness range of 2.7⁻4.1 N and can withstand normal stresses but are also flexible to prevent damage to newly formed skin tissues. Wafers were porous (SEM) with pore sizes ranging from 78.8 to 141 µm, and BSs were not visible on the wafer surface or pore walls. The BSs enhanced the porosity of the wafers with values above 98%, while the Aw and EWC ranged from 2699⁻3569% and 96.58⁻98.00%, respectively. The EWL ranged from 85 to 86% after 24 h while the WVTR ranged from 2702⁻3080 g/m² day-1. The compatibility of BSs within the CARR-SA matrix was confirmed by seven characteristic functional groups which were consistently transmitted in the ATR-FTIR spectra. These novel medicated dressing prototypes can potentially help to achieve more rapid wound healing.


Do rational numbers play a role in selection for stochasticity?
When a given tissue must, to be able to perform its various functions, consist of different cell types, each fairly evenly distributed and with specific probabilities, then there are at least two quite different developmental mechanisms which might achieve the desired result. Let us begin with the case of two cell types, and first imagine that the proportion of numbers of cells of these types should be 1:3. Clearly, a regular structure composed of repeating units of four cells, three of which are of the dominant type, will easily satisfy the requirements, and a deterministic mechanism may lend itself to the task. What if, however, the proportion should be 10:33? The same simple, deterministic approach would now require a structure of repeating units of 43 cells, and this certainly seems to require a far more complex and potentially prohibitive deterministic developmental program. Stochastic development, replacing regular units with random distributions of given densities, might not be evolutionarily competitive in comparison with the deterministic program when the proportions should be 1:3, but it has the property that, whatever developmental mechanism underlies it, its complexity does not need to depend very much upon target cell densities at all. We are immediately led to speculate that proportions which correspond to fractions with large denominators (such as the 33 of 10/33) may be more easily achieved by stochastic developmental programs than by deterministic ones, and this is the core of our thesis: that stochastic development may tend to occur more often in cases involving rational numbers with large denominators. To be imprecise: that simple rationality and determinism belong together, as do irrationality and randomness.


Survival after oxaliplatin therapy of irinotecan-pretreated advanced colorectal cancer patients.
The activity of oxaliplatin (OHP) and irinotecan (CPT) alone or in combination with 5-fluorouracil (5-FU) in advanced colorectal cancer is comparable, but there are limited data on the effectiveness of oxaliplatin in patients pretreated by irinotecan. We have analyzed retrospectively the survival of 77 consecutive advanced colorectal cancer patients treated with OHP after previous CPT therapy. Multivariate analysis was performed by Cox regression method, with the results expressed as hazard ratio (HR). The median survival from the start of OHP therapy was 10.7 months (1-year survival 43%). The median survival was not reached in 10 patients treated by hepatic arterial infusion of OHP (>10.6 months). The median survival from the diagnosis of advanced/metastatic disease was 34.3 months. On multivariate analysis, hemoglobin <125g/L (HR=2.42), neutrophils <5200 per microL (HR=0.36), duration of advanced/metastatic disease <21 months (HR=2.40) and interval from last CPT administration <3 months (HR=0.27) were statistically significant (p<0.05) independent predictors of survival from the start of OHP treatment, but only hemoglobin (HR=2.07), neutrophils (HR=0.32) and CEA <100microg/L (HR=0.44) were independent predictors of survival from the last CPT. There were 4 treatment-induced deaths after combination of OHP and raltitrexed (TOMOX). More than 40% of patients pretreated by irinotecan survived 1 year after start of OHP therapy. The therapy was similarly effective as a second or higher line of treatment. Hemoglobin levels and neutrophil count were independent factors associated with survival. The number of toxic deaths observed after TOMOX is alarming.


A Biotechnological Review on Patents Applied to Rubella Diagnosis.
Rubella, caused by the Rubella virus (RV), is considered a mild self-limited illness. However, RV has teratogenic potential. Laboratory investigation plays an important role in both diagnosis and surveillance of the disease. The main methods for diagnosing Rubella are serological assays for the detection of specific IgM and molecular assays for detecting viral RNA. However, some laboratories perform IgG avidity testing, virus isolation and analysis of genetic sequence as tools to help Rubella eradication. The importance of the diagnosis of Rubella involves the appropriate treatment of the disease, because the Rubella clinical symptoms may be similar to those of other diseases, and the population monitoring to avoid new emergent cases. This study addresses different methods of diagnosing Rubella and contributes as a source of knowledge to assist health systems in controlling the disease. The main objective of this study was to review the available patents regarding Rubella diagnosis published in intellectual property databases, and provides an overview of the technologies available for the diagnosis of Rubella. The search strategy was based on the keywords searched separately or together using a Boolean operator either in the patent title or abstract the time interval was restricted to patents filed or granted from January 2009 until February 2022. The database used was Google Patents. This study analyzed 24 patent documents regarding strategies for the diagnosis of Rubella. Of these, 15 patents disclose strategies for detecting Rubella antibodies, 7 patents the detection of Rubella virus nucleic acid, and 2 patents the production of antibodies applied in Rubella diagnosis. Rubella is still a public health problem in some countries, mainly those in development, especially due to congenital Rubella syndrome, which can cause malformation or fetal death. However, its diagnosis is challenging, due to similarity of symptoms with other diseases, and for this reason, laboratory diagnosis is essential. Studies like this encourage researchers and governments to invest in research to continue the development of new products, using different areas of biotechnology, to solve society's problems, especially diseases that have an impact on global health, such as Rubella.


Possessive objects and paralyzing moods.
This article focuses on unique being states of mental and physical paralysis among schizophrenic patients. These paralyzing moods derive from continuous extractive introjections, in which anything alive in the patient is sucked out, as it were, by an internalized possessive object. Continuous extractive introjections early in life constitute attacks on authentic expression of the child's subjectivity, and prevent the development of his idiom and the unthought known. A clinical vignette is presented to illustrate certain movements both in a progressive direction (i.e., in psychoanalytic treatment) and in a retrogressive direction (in the formation of the original psychotic pathology).


An unusual cause of recurrent abdominal pain.
Abdominal pain is a common complaint with diverse etiologies. We describe an unusual case of recurrent abdominal pain in an adult due to lead poisoning, a condition usually associated with childhood. A previously healthy 42-yr-old man presented with 2 days of severe crampy abdominal pain and a 1-month history of constipation. Physical examination was remarkable for diffuse abdominal pain but peritoneal signs were not present. Blood tests were remarkable for hematocrit of 33 and mean cell volume of 78, with ovalocytes and basophilic stippling on blood smear. Abdominal x-ray showed stool throughout the colon and a nonspecific bowel gas pattern. The patient was treated with intravenous fluids and enemas, and his symptoms resolved within 2 days. Repeat history taking revealed he had been stripping paint from an old Victorian house in the preceding few months. He was discharged after a blood lead level was obtained. Before his clinic appointment he was readmitted 2 days later with recurrent abdominal pain. His blood lead level was elevated at 110 microg/dl (toxic range). After consultation with the Occupational Health and Safety Administration and local poison control service, he was treated with intravenous calcium edetate disodium and intramuscular dimercaprol. He was asymptomatic at discharge, with a level of 56 microg/dl. Two weeks later, a repeat level was elevated at 72 microg/dl, for which he received a 3-wk course of oral dimercaptosuccimer. Subsequent levels were unremarkable, and the patient remains asymptomatic. Abdominal pain secondary to lead poisoning in adults is uncommon. This case highlights the importance of taking a detailed occupational history and appropriately using "routine" blood tests to diagnose a rare condition that presented with a common complaint.


[Primary dural lymphoma. A case report].
Primary central nervous system lymphoma is an invasive disease in both HIV-positive and HIV-negative patients. Atypical presentations, including leptomeningeal involvement often described in cases with aggressive histology, have been reported but primary meningeal B-cell lymphoma appears to be very rare. A 40-year-old immunocompetent man developed a voluminous frontoparietal cranial vault tumor. The neurology examination demonstrated a large extra-axial mass involving the anterior part of the superior longitudinal sinus. The tumor extended through the cranial vault, without osteolysis, and grew in the subcutaneous tissue. Craniotomy was performed and the entire mass was resected without neurological deterioration. Pathology reported B-cell lymphoma. No other localization was found. Primary B-cell meningeal lymphoma, as illustrated in this case, can be another atypical presentation of CNS lymphoma.


Learning effects of a workshop in palliative cancer care for general practitioners.
Cancer patients may unnecessarily suffer from pain and other symptoms due to insufficient knowledge on the part of their doctors. In The Netherlands, the general practitioner is considered to be the key provider of palliative care for the cancer patient. Therefore, the authors developed and conducted workshops to teach symptom control to general practitioners. These workshops contained learning objectives from which they selected 18 items to form a questionnaire with five-point response scales. The goal of this study was to investigate changes in the knowledge and attitude scores of the participating general practitioners. The participants were asked to complete the questionnaire at the start of the workshop and also four months later. Responses were obtained from 120 general practitioners for the pre-workshop and 96 for the post-workshop questionnaires. The majority of the scores increased toward the desired effect, and some items' scores improved by almost two points. The results suggest improvements in general practitioners' knowledge and attitude scores with regard to cancer pain and symptom management. Future studies should try to link these improvements with quality-of-life parameters of terminal cancer patients and their families.


Adult Medulloblastoma Depicted With 99mTc-HYNIC-[D-Phe1, Tyr3-Octreotide] SPECT/CT.
Although medulloblastoma constitutes the second most common malignant brain tumor in children, it encountered very rarely in adults. The incidence of adult medulloblastoma is approximately 0.6 to 1 case per million. It accounts for less than 1% of adult brain tumors and is located most commonly at the posterior cranial fossa. We present an extremely rare case of a 67-year-old man with cerebellar medulloblastoma with residual disease after surgery, chemotherapy, and radiation therapy, depicted with Tc-HYNIC-[D-Phe, Tyr-Octreotide] SPECT/CT. Somatostatin receptor scintigraphy was performed for staging and for the possibility of treatment with somatostatin analogs or peptide radionuclide therapy.


Osteoporosis in men and women: a story about bone mineral density thresholds and hip fracture risk.
In postmenopausal women, the T score for bone mineral density (BMD) is a well-accepted diagnostic criterion for osteoporosis. It is also used to assess fracture risk. However, it is unclear whether in elderly men similar BMD thresholds should be used. Different hypotheses have been proposed for the relation of BMD with hip fracture risk in men. In this study, we tested those hypotheses using a mathematical model and we compared the calculated results with observed prospective data from the Rotterdam study. In the model, we combined the observed femoral neck BMD distribution for men and women with previously derived hip fracture risk functions based on age and BMD. For men, we tested different hypotheses for the relation of BMD with hip fracture risk. The relation of BMD with hip fracture risk is similar in men and women (scenario 1) or the relative risk (RR) per standard deviation (SD) decrease of BMD is either larger or smaller in men than in women (scenario 2a and 2b), or, at a similar absolute fracture risk, men have a higher BMD (scenario 3). In the prospective data, men with a hip fracture had an average BMD that was 0.070 g/cm2 higher than women with a hip fracture. The calculated results from the first scenario were consistent with those data and were also consistent with the observed hip fracture incidence and the observed female-to-male (F/M) risk ratio (1.7). When the RR for each SD decrease of BMD was assumed to be either larger or smaller in men than in women (second scenario), the calculated average BMD difference in men and women became respectively smaller or larger than observed. When men would have a higher fracture risk at similar BMD levels (third scenario), the calculated total number of hip fractures increased and even exceeded that in women, with an F/M risk ratio of 0.94 in our example. In women, a larger proportion of hip fractures occurs at a T score below -2.5 than in men using the same absolute BMD threshold, but using a male-specific T score largely solves this diagnostic problem. Taken together, the average hip fracture risk in men is much lower than in women but appeared to be similar at the same BMD. Therefore, we propose the use of the same absolute BMD thresholds for decisions about interventions.


Efficacy of laser acupuncture for patients with chronic Bell's palsy: A study protocol for a randomized, double-blind, sham-controlled pilot trial.
Bell's palsy is the most frequent cause of unilateral peripheral facial palsy, a common condition that third of patients can have inadequate recovery and subsequent physical and social impairments. The largely ineffective and even controversial nature of the various medical and surgical treatment options means that novel, alternative approaches are needed. In preclinical and clinical evidence, low-level laser therapy (LLLT) has demonstrated the ability to regenerate peripheral nerves. Laser acupuncture treatment (LAT), the stimulation of traditional acupoints with low-intensity, non-thermal laser irradiation, is a common treatment modality, but its efficacy in chronic Bell's palsy is undetermined. This study aims to evaluate the efficacy of LAT in patients experiencing inadequate recovery from Bell's palsy. This 2-armed, parallel, randomized, subject-assessor-blinded, single-center, sham-controlled pilot trial will randomly assign 32 eligible patients into either a real LAT group (n = 16) or a sham LAT group (n = 16). The real LAT group will receive 3 LAT sessions each week for 6 weeks (a total of 18 sessions), delivered to acupoints corresponding with the affected side of the face. The sham LAT group will receive the same treatment as the real LAT group, but with a sham laser device. The primary outcome measure will be the change from baseline at week 6 in the Facial Disability Index score. Secondary outcomes will monitor changes during treatment in the House-Brackmann and Sunnybrook facial nerve grading systems and stiffness scale, at weeks 1, 3, and 6. To the best of our knowledge, this double-blind, randomized, sham-controlled trial is the first such investigation into the efficacy of LAT in chronic Bell's palsy. Clinical trials using LLLT have shown positive therapeutic effects in acute Bell's palsy, although as yet, the feasibility and efficacy of LAT remain unclear in patients experiencing inadequate recovery from Bell's palsy. This trial protocol has been approved by the Research Ethics Committee of the China Medical University Hospital, Taichung, Taiwan (Protocol ID: CMUH107-REC1-030) also registered at ClinicalTrials.gov (identifier no. NCT03592797).


Acceptance and commitment therapy for breast cancer survivors with fear of cancer recurrence: A 3-arm pilot randomized controlled trial.
Fear of cancer recurrence (FCR) has a profound negative impact on quality of life (QOL) for many cancer survivors. Breast cancer survivors (BCS) are particularly vulnerable, with up to 70% reporting clinically significant FCR. To the authors' knowledge, evidence-based interventions for managing FCR are limited. Acceptance and commitment therapy (ACT) promotes psychological flexibility in managing life's stressors. The current study examined the feasibility and preliminary efficacy of group-based ACT for FCR in BCS. Post-treatment BCS (91 patients with stage I-III disease) with clinical FCR randomly were assigned to ACT (6 weekly 2-hour group sessions), survivorship education (SE; 6 weekly 2-hour group sessions), or enhanced usual care (EUC; one 30-minute group coaching session with survivorship readings). FCR severity (primary outcome) and avoidant coping, anxiety, post-traumatic stress, depression, QOL, and other FCR-related variables (secondary outcomes) were assessed at baseline (T1), after the intervention (T2), 1 month after the intervention (T3), and 6 months after the intervention (T4) using intent-to-treat analysis. Satisfactory recruitment (43.8%) and retention (94.5%) rates demonstrated feasibility. Although each arm demonstrated within-group reductions in FCR severity over time, only ACT produced significant reductions at each time point compared with baseline, with between-group differences at T4 substantially favoring ACT over SE (Cohen d for effect sizes, 0.80; P < .001) and EUC (Cohen d, 0.61; P < .01). For 10 of 12 secondary outcomes, only ACT produced significant within-group reductions across all time points. By T4, significant moderate to large between-group comparisons favored ACT over SE and EUC with regard to avoidant coping, anxiety, depression, QOL, and FCR-related psychological distress. Group-based ACT is a feasible and promising treatment for FCR and associated outcomes in BCS that warrants testing in larger, fully powered trials.


Nafadotride administration increases D1 and D1/D2 dopamine receptor mediated behaviors.
The administration of nafadotride, given at doses known to block the D3 dopamine receptors (0.75, 1.5, 3 mg/kg i.p.) increased locomotor activity both in naive and habituated rats and counteracted the hypothermia but not the hypomotility induced by a low dose of the putative D3 dopamine agonist (+/-)-7-hydroxy-2-(di-N-propylamino)-tetralin (7-OH-DPAT; 0.04 mg/kg). Nafadotride did not antagonize either the motor effects induced by different doses of the D2 agonist quinpirole (0.05 and 0.3 mg/kg) or the hypermotility induced by 7-OH-DPAT given at a dose (0.32 mg/kg) stimulating D2 dopamine receptors. The same nafadotride doses potentiated the grooming behavior induced by the D1 dopamine agonist SKF 38393 (10 mg/kg i.p.) as well as the stereotyped response to the D1/D2 agonist apomorphine (0.5 mg/kg s.c.). Stereotyped behavior was also observed in rats concomitantly treated with nafadotride and the D2 agonist quinpirole. As the activation of D1 dopamine receptors plays an important role in the occurrence of stereotypies, the results suggest that the blockade of D3 receptors by nafadotride could have favored D1/D2 dopamine receptor-mediated behaviors by potentiating D1 receptor function.


Fluorescence polarization immunoassay of a high-molecular-weight antigen using a long wavelength-absorbing and laser diode-excitable metal-ligand complex.
We describe a fluorescence polarization immunoassay (FPI) based on an osmium metal-ligand complex, Os(bpy)2(dcbpy). The Os complex was selected for its long wavelength absorption, which allows excitation with wavelengths up to 720 nm. At these wavelengths tissue absorbance and autofluorescence are minimal, and excitation can be accomplished with LEDs or laser diodes. The Os complex displays a lifetime of 19 ns and a high initial anisotropy at two excitation wavelengths, 505 and 690 nm. A reactive NHS-ester of Os- (bpy)2(dcbpy) was synthesized containing a NHS ester, and used to label the human serum albumin (HSA) or anti-HSA. The FPIs of HSA were performed with monoclonal and polyclonal antibodies using excitation at 505 or 685 nm. The results showed the potential of the Os-ligand complex to be used as a long excitation wavelength FPI probe for potential use in homogeneous immunoassays with simple excitation sources.


Effect of Cross Theoretical Model of Behaviour Change and Motivation Interview on Self-Management Behaviour.
To evaluate the effects of a trans-theoretical model (TTM) of behavioural change plus motivational interviewing on self-management behavior and quality of life (QoL) in patients with intracranial aneurysm. A total of 94 patients with intracranial aneurysm treated in the First Affiliated Hospital of Wenzhou Medical University from 2019 to 04/2021-04 were retrospectively analyzed. Among them, 49 patients used TTM + motivational interview as the observation group (Obs group), and 45 patients used the traditional method as the control group (Con group). The Self-Management Behavior Scale for Patients with Intracranial Aneurysm was used for analyzing the changes in the self-management behavior of the two groups of patients, and the MOS 36-item Short Form Health Survey (SF-36) was used to analyze the changes in the QoL of the patients. The incidence of adverse events after 6 months of intervention was counted. In addition, the Barthel Index (BI) and Montreal Cognitive Assessment Scale (MOCA) were used to evaluate the recovery effects of patients. Logistic regression was conducted for analyzing the risk factors of adverse cerebrovascular events. After treatment, the Con group got lower self-management behavior score than the Obs group (P < 0.05), and also got lower SF-36 scores, BI, and MOCA scores than the Obs group (P < 0.05). Age and a history of hypertension were independent risk factors for adverse events. The Hosmer-Lemeshow test was adopted for testing the goodness of fit of the regression equation (P=0.903). With the established model, the area under the receiver operating characteristic curve for predicting adverse events in patients with intracranial aneurysm was determined to be 0.851, indicating that the model performed well as a risk prediction model. TTM + motivational interviewing can help improve the self-management behavior and QoL of patients with intracranial aneurysm without increasing the occurrence of adverse events.


Verbal learning in amnesic anterior communicating artery aneurysm patients and in patients with multiple sclerosis.
The California Verbal Learning Test (CVLT) was used to examine the qualitative, and quantitative aspects of memory in patients with amnesic anterior communicating artery aneurysm (ACoA) and in patients with multiple sclerosis (MS). The results show that both groups were impaired relative to control participants with respect to acquisition of verbal material. The participants with A CoA exhibited a profound loss of information and emitted a significantly greater number of intrusions and false positives than either control participants or participants with MS. The advantages of using both quantitative and qualitative measures of memory in differentiating various clinical populations are discussed.


Professional ethics and managed care in dermatology.
The way health care is financed in the United States is changing quickly. Fee-for-service arrangements in which health care providers exercised great autonomy over health care services financed by third-party payers is quickly giving way to a variety of managed care approaches. The driving force behind this change is the desire to control the growth of health care cost. In the simplest term, costs are controlled in a managed care system by controlling the provision of services. Broadly speaking, 1 of 2 methods is used to control costs. Either physician behavior or subscriber behavior is modified or limited.


Sounds to Astound: An acoustics outreach show.
Sounds to Astound is an acoustics demonstration show, produced for the community twice yearly by the Brigham Young University Student Chapter of the Acoustical Society of America. The free, interactive demonstration show explores the science of sound for a target audience of fifth- to eighth-grade students. Introductory acoustics concepts, such as longitudinal wave motion, wave properties, propagation effects, and standing waves, are taught with live demonstrations, animations, and videos. The goal of this paper is to inspire and encourage readers in their outreach efforts by describing the purposes of Sounds to Astound and technical details of several entertaining and educational demonstrations. Lessons learned from a decade of these student-produced shows serve as an aid for future efforts and highlight the benefits of outreach efforts, particularly for the students involved.


Phosphatidylinositol 4-kinase III beta is essential for replication of human rhinovirus and its inhibition causes a lethal phenotype in vivo.
Human rhinovirus (HRV) is the predominant cause of the common cold, but more importantly, infection may have serious repercussions in asthmatics and chronic obstructive pulmonary disorder (COPD) patients. A cell-based antiviral screen against HRV was performed with a subset of our proprietary compound collection, and an aminothiazole series with pan-HRV species and enteroviral activity was identified. The series was found to act at the level of replication in the HRV infectious cycle. In vitro selection and sequencing of aminothiazole series-resistant HRV variants revealed a single-nucleotide mutation leading to the amino acid change I42V in the essential HRV 3A protein. This same mutation has been previously implicated in resistance to enviroxime, a former clinical-stage antipicornavirus agent. Enviroxime-like compounds have recently been shown to target the lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIIIβ). A good correlation between PI4KIIIβ activity and HRV antiviral potency was found when analyzing the data over 80 compounds of the aminothiazole series, covering a 750-fold potency range. The mechanism of action through PI4KIIIβ inhibition was further demonstrated by small interfering RNA (siRNA) knockdown of PI4KB, which reduced HRV replication and also increased the potency of the PI4KIIIβ inhibitors. Inhibitors from two different structural classes with promising pharmacokinetic profiles and with very good selectivity for PI4KIIIβ were used to dissociate compound-related toxicity from target-related toxicity. Mortality was seen in all dosing groups of mice treated with either compound, therefore suggesting that short-term inhibition of PI4KIIIβ is deleterious.


Pest control and resistance management through release of insects carrying a male-selecting transgene.
Development and evaluation of new insect pest management tools is critical for overcoming over-reliance upon, and growing resistance to, synthetic, biological and plant-expressed insecticides. For transgenic crops expressing insecticidal proteins from the bacterium Bacillus thuringiensis ('Bt crops') emergence of resistance is slowed by maintaining a proportion of the crop as non-Bt varieties, which produce pest insects unselected for resistance. While this strategy has been largely successful, multiple cases of Bt resistance have now been reported. One new approach to pest management is the use of genetically engineered insects to suppress populations of their own species. Models suggest that released insects carrying male-selecting (MS) transgenes would be effective agents of direct, species-specific pest management by preventing survival of female progeny, and simultaneously provide an alternative insecticide resistance management strategy by introgression of susceptibility alleles into target populations. We developed a MS strain of the diamondback moth, Plutella xylostella, a serious global pest of crucifers. MS-strain larvae are reared as normal with dietary tetracycline, but, when reared without tetracycline or on host plants, only males will survive to adulthood. We used this strain in glasshouse-cages to study the effect of MS male P. xylostella releases on target pest population size and spread of Bt resistance in these populations. Introductions of MS-engineered P. xylostella males into wild-type populations led to rapid pest population decline, and then elimination. In separate experiments on broccoli plants, relatively low-level releases of MS males in combination with broccoli expressing Cry1Ac (Bt broccoli) suppressed population growth and delayed the spread of Bt resistance. Higher rates of MS male releases in the absence of Bt broccoli were also able to suppress P. xylostella populations, whereas either low-level MS male releases or Bt broccoli alone did not. These results support theoretical modeling, indicating that MS-engineered insects can provide a powerful pest population suppressing effect, and could effectively augment current Bt resistance management strategies. We conclude that, subject to field confirmation, MS insects offer an effective and versatile control option against P. xylostella and potentially other pests, and may reduce reliance on and protect insecticide-based approaches, including Bt crops.


Preoperative cardiac variables of diastolic dysfunction and clinical outcomes in lung transplant recipients.
Background. Orthotopic lung transplantation is now widely performed in patients with advanced lung disease. Patients with moderate or severe ventricular systolic dysfunction are typically excluded from lung transplantation; however, there is a paucity of data regarding the prognostic significance of abnormal left ventricular diastolic function and elevated pretransplant pulmonary pressures. Methods. We reviewed the characteristics of 111 patients who underwent bilateral and unilateral lung transplants from 200 to 2009 in order to evaluate the prognostic significance of preoperative markers of diastolic function, including invasively measured pulmonary capillary wedge pressure (PCWP) and echocardiographic variables of diastolic dysfunction including mitral A > E and A' > E'. Results. Out of 111 patients, 62 were male (56%) and average age was 54.0 ± 10.5 years. Traditional echocardiographic Doppler variables of abnormal diastolic function, including A' > E' and A > E, did not predict adverse events (P = 0.49). Mildly elevated pretransplant PCWP (16-20 mmHg) and moderately/severely elevated PCWP (>20 mmHg) were not associated with adverse clinical events after transplant (P = 0.30). Additionally, all clinical endpoints did not show any statistical significance between the two groups. Conclusions. Pre-lung transplant invasive and echocardiographic findings of elevated pulmonary pressures and abnormal left ventricular diastolic function are not predictive of adverse posttransplant clinical events.


Outcome of Early Juvenile Onset Metachromatic Leukodystrophy After Unrelated Cord Blood Transplantation: A Case Series and Review of the Literature.
The purpose of this study was to determine whether transplantation of umbilical cord blood from unrelated donors before the development of symptoms could halt the progression of early juvenile onset cases of MLD in whom the disease was diagnosed based on the family history. Three asymptomatic children (aged 2 years 4 months, 2 years 8 months and 5 years 5 months, two of whom were sisters) underwent unrelated umbilical cord blood transplantation (UCBT) and two untreated symptomatic siblings were included in the study. In 14-year and 6-year follow-ups after transplantation, clinical examination, ARSA enzyme levels, neurophysiological, neuroimaging, and psychological status were assessed. All three transplanted patients remain well, and the parameters evaluated remain stable. Of the treated patients, the two sisters had ongoing evidence of demyelinating sensorimotor neuropathy on nerve conduction tests, and with a early sensorimotor neuropathy in the older sister , and the other patient has mild intellectual impairment. One of the two un-transplanted controls, 15 years after MLD diagnosis, has relentlessly progressed to full dependency with epilepsy, severe mental retardation, dystonic movements, dysphagia and recurrent respiratory problems. Six years after diagnosis, the other control has a slowly progressive course with spastic dystonic quadriplegia, epilepsy, dysphagia, continual drooling and incontinence. Our data show that, in comparison with their untreated siblings, UCBT significantly slowed the progression of the disease in the treated patients. We conclude that UCBT benefits children with pre-symptomatic early juvenile onset MLD by favourably altering the natural history of the disease.


Antioxidant and toxicological evaluation of Cassia sopherain streptozotocin-induced diabetic Wistar rats.
Multiple-organ failure is the main cause of death in diabetes mellitus (DM). Hyperglycemia-induced oxidative stress is responsible for major diabetic complications, including multiple-organ failure. Medicinal plants possessing antioxidant activity may reduce oxidative stress and improve the functions of various organs affected by hyperglycemia. This study was designed to evaluate the antioxidant effect of Aqueous Extract of Cassia sophera (AECS) in streptozotocin (STZ)-induced diabetic Wistar rats. AECS (200 mg/kg body weight (bw)) and the standard antidiabetic drug glibenclamide (10 mg/kgbw) were administered orally by gavaging for 28 days. Oral administration of AECS inhibited STZ-induced increase in lipid peroxidation (LPO), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), bilirubin, creatinine and urea in liver of diabetic rats. Significant increase in activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and a reduced level of glutathione (GSH), were observed in the liver, kidney, pancreas and testis on AECS treatment. The results demonstrate that AECS is not only useful in controlling blood glucose, but also has antioxidant potential to protect the liver, kidney, pancreas and testis against damage caused by hyperglycemia-induced oxidative stress.


[Retinal vascular occlusion and primary antiphospholipid syndrome. Report of 2 cases].
The antiphospholipid syndrome is characterized by the association of antiphospholipid antibodies and occlusive vascular events. The ocular vascular damage is described in the literature and may reveal the syndrome. It's diagnosis is important because this disease, which generally affects young people, may endanger ocular and vital prognosis. Two cases are reported. Two young people aged 22 and 32 presented with a sudden unilateral loss of vision. In both cases, fundus examination and fluorescein angiography revealed a severe retinal vascular occlusion. For one patient, an antiphospholipid syndrome was discovered during etiological check-up. for the second one, it was associated with a heterozygote state mutation of Leiden V factor. In both cases the visual function of the affected eye was lost. In most cases central artery or vein occlusion means atherosclerosis. However, other etiologies must be studied in young patients. According to several studies: antiphospholipid syndrome has been detected in 5% to 33% of the patients showing a major vascular retinal obstruction. The association of thrombophilia must be considered because it increases the risk of thrombotic recurrence. The antiphospholipid syndrome must be studied in cases of numerous and severe retinal vascular obstruction occurring in young patients, even if vascular risks exist. This diagnosis is important because it may imply a long-lasting anticoagulative or an antiaggregative treatment to significantly reduce the risk of recurrent thrombotic events.


[Strongyloidosis. Part VI animal models].
Animal models (rat, mouse, dog and monkey) being used in comparative investigations on immunobiology, pathology, clinical manifestations and treatment ot human atrongyloidosis were presented.


Estimation of the frequency of malformed sperm by slit scan flow cytometry.
We have investigated the utility of Slit Scan Flow Cytometry (SSFCM) for measuring the frequencies of malformed sperm heads in control and mutagen treated B6C3F1/CRL mice. In SSFCM, fluorescence profiles of sperm heads stained with the DNA-specific fluorescent dye acriflavine were recorded for sperm flowing lengthwise through a 2.5-microns-thick laser beam. Malformed sperm were detected as having fluorescence profiles that differed substantially from an average fluorescence profile for sperm from untreated mice. Specifically, a sum of squared difference (SSD) value was calculated for the fluorescence profile of each sperm according to the equation (Formula: see text) where c(i) and t(i) are the ith values for the fluorescence profiles from control and test sperm, respectively. Profiles whose SSD exceeded a threshold value of 20 were considered to be from malformed sperm. We measured fluorescence profiles for 500 sperm per mouse from five control mice, five mice injected intraperitoneally daily for 5 days with a total of 375 mg/kg of body weight methyl methane sulfonate (MMS), and for 30 mice injected intraperitoneally daily for 5 days with total doses of procarbazine ranging from 125 mg/kg to 1,250 mg/kg. Sperm were collected from the caudae epididymides 35 days after the last injection. Frequencies of malformed sperm in these samples were also estimated by visual analysis. All samples were analyzed in double blind fashion. The visual and SSFCM malformed sperm frequencies for the samples from control, MMS-treated, and procarbazine-treated mice were correlated (r = 0.83). A dose effect was seen with both the visual and SSFCM estimates for the sperm from the procarbazine-treated mice.


New concepts and applications in the macromolecular chemistry of fullerenes.
A new classification on the different types of fullerene-containing polymers is presented according to their different properties and applications they exhibit in a variety of fields. Because of their interest and novelty, water-soluble and biodegradable C(60)-polymers are discussed first, followed by polyfullerene-based membranes where unprecedented supramolecular structures are presented. Next are compounds that involve hybrid materials formed from fullerenes and other components such as silica, DNA, and carbon nanotubes (CNTs) where the most recent advances have been achieved. A most relevant topic is still that of C(60)-based donor-acceptor (D-A) polymers. Since their application in photovoltaics D-A polymers are among the most realistic applications of fullerenes in the so-called molecular electronics. The most relevant aspects in these covalently connected fullerene/polymer hybrids as well as new concepts to improve energy conversion efficiencies are presented.The last topics disccused relate to supramolecular aspects that are in involved in C(60)-polymer systems and in the self-assembly of C(60)-macromolecular structures, which open a new scenario for organizing, by means of non-covalent interactions, new supramolecular structures at the nano- and micrometric scale, in which the combination of the hydrofobicity of fullerenes with the versatility of the noncovalent chemistry afford new and spectacular superstructures.


The critical evaluation of laser Doppler imaging in determining burn depth.
This review article discusses the use of laser Doppler imaging as a clinimetric tool to determine burn depth in patients presenting to hospital. Laser Doppler imaging is a very sensitive and specific tool to measure burn depth, easy to use, reliable and acceptable to the patient due to its quick and non-invasive nature. Improvements in validity, cost and reproducibility would improve its use in clinical practice however it is difficult to satisfy the entire evaluation criterion all the time. It remains a widely accepted tool to assess burn depth, with an ever-increasing body of evidence to support its use, as discussed in this review. Close collaboration between clinicians, statisticians, epidemiologists and psychologists is necessary in order to develop the evidence base for the use of laser Doppler imaging as standard in burn depth assessment and therefore act as an influencing factor in management decisions.


Fetal and infant growth and asthma symptoms in preschool children: the Generation R Study.
Low birth weight is associated with an increased risk of wheezing in childhood. We examined the associations of longitudinally measured fetal and infant growth patterns with the risks of asthma symptoms in preschool children. This study was embedded in a population-based prospective cohort study among 5,125 children. Second- and third-trimester fetal growth characteristics (head circumference, femur length, abdominal circumference, and weight) were estimated by repeated ultrasounds. Infant growth (head circumference, length, and weight) was measured at birth and at the ages of 3, 6, and 12 months. Parental report of asthma symptoms until the age of 4 years was yearly obtained by questionnaires. Both fetal restricted and accelerated growth, defined as a negative or positive change of more than 0.67 standard deviation score, were not associated with asthma symptoms until the age of 4 years. Accelerated weight gain from birth to 3 months following normal fetal growth was associated with increased risks of asthma symptoms (overall odds ratio for wheezing: 1.44 [95% confidence interval: 1.22, 1.70]; shortness of breath: 1.32 [1.12, 1.56]; dry cough: 1.16 [1.01, 1.34]; persistent phlegm: 1.30 [1.07, 1.58]), but not with eczema (0.95 [0.80, 1.14]). These associations were independent of other fetal growth patterns and tended to be stronger for children of atopic mothers than for children of nonatopic mothers. Weight-gain acceleration in early infancy was associated with increased risks of asthma symptoms in preschool children, independent of fetal growth. Early infancy might be a critical period for the development of asthma.


Recovery of Chromium(VI) Ions Using a Nickel-Aluminum-Zirconium Complex Hydroxide Based on Adsorption and Desorption Treatment.
In this study, we evaluate the desorption or recovery capacity of chromium(VI) ions using desorption solutions containing sodium hydroxide (NaOH) or sodium sulfate (Na2SO4). A complex hydroxide of nickel-aluminum-zirconium (NAZ) was prepared as the adsorbent for the removal of chromium(VI) ions. The results from repeated adsorption/desorption experiments on chromium(VI) ions using NAZ complex hydroxide were evaluated. The desorption percentage of chromium(VI) ions increased with the increase in the concentration of NaOH or Na2SO4 in the desorption solution. The determined optimal concentration of NaOH or Na2SO4 in the desorption solution was 10 mmol/L under the used experimental conditions. After three adsorption-desorption cycles, the recovery percentages of chromium(VI) ions using NaOH and Na2SO4 were 60% (total amounts adsorbed and desorbed were 102 and 61 mg/g, respectively) and 75% (total amounts adsorbed and desorbed were 96 and 72 mg/g, respectively), respectively. Additionally, we confirmed the existence of chromium on the surface of the NAZ complex hydroxide. After three adsorption/desorption cycles, the crystal structure of the NAZ complex hydroxide was maintained. These results indicated the potential of the NAZ complex hydroxide using a desorption solution containing NaOH or Na2SO4 for the recovery of chromium(VI) ions.


Pharmacovigilance-related topics at the level of the International Conference on Harmonisation (ICH).
Marketing authorisations for medicines need to be based on the universal criteria quality, safety and efficacy, whilst taking into account local public health needs. With view to using resources efficiently and avoiding delay in access to medicines, scientific standards for investigating quality, safety and efficacy should be universal too. A major step to achieve this was taken in 1990 when the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) was established between authorities and industry in the European Union (EU), Japan and the United States. Since then more than 50 ICH Guidelines have been published, out of which six are specific to pharmacovigilance. They refer to management and expedited reporting of individual adverse drug reaction (ADR) cases, including electronic formats, periodic reporting of worldwide data and planning of pharmacovigilance. Their development has to be seen in the context of initiatives taken in the three ICH Regions to strengthen pharmacovigilance. Most recently this involves making use of risk management concepts, reflecting new thinking of proactivity in pharmacovigilance. Moreover, consideration is given to regional and international cooperation beyond the ICH Regions.


Leapfrog Group patient safety initiatives draw kudos, criticism.
Just over a year ago, the Leapfrog Group proposed a three-pronged patient safety initiative. One year later, the group is finding that many hospitals and health systems across the country are looking closely at the recommendations and making changes. But, it also is finding that it has become a lightning rod within the health care community in debates on whether these proposals are the best way now to proceed in improving patient safety.


Is Earth a perfect square? Repetition increases the perceived truth of highly implausible statements.
A single exposure to statements is typically enough to increase their perceived truth. This Truth-by-Repetition (TBR) effect has long been assumed to occur only with statements whose truth value is unknown to participants. Contrary to this hypothesis, recent research has found that statements contradicting participants' prior knowledge (as established from a first sample of participants) show a TBR effect following their repetition (in a second, independent sample of participants). As for now, however, attempts at finding a TBR effect for blatantly false (i.e., highly implausible) statements have failed. Here, we reasoned that highly implausible statements such as Elephants run faster than cheetahs may show repetition effects, provided a sensitive truth measure is used and statements are repeated more than just once. In a preregistered experiment, participants judged on a 100-point scale the truth of highly implausible statements that were either new to them or had been presented five times before judgment. We observed an effect of repetition: repeated statements were judged more true than new ones, although all judgments were judged below the scale midpoint. Exploratory analyses additionally show that about half the participants showed no or even a reversed effect of repetition. The results provide the first empirical evidence that repetition can increase perceived truth even for highly implausible statements, although not equally so for all participants and not to the point of making the statements look true.


Effect of somatostatin on renal function.
Somatostatin has profound effects on both splanchnic and portal vascular beds. The effects of intravenous somatostatin (100 micrograms/h) on urinary volume, effective renal plasma flow, and glomerular filtration rate were compared with the effects of a control infusion of physiological saline in six normal subjects. Renal plasma flow and glomerular filtration rate were measured by primed constant isotope infusions of iodine-125 iodohippurate and chromium-51 edetic acid. Urinary volume, renal plasma flow, and glomerular filtration rate were measured during 20 minute clearance periods. During the control infusion urinary volume, renal plasma flow, and glomerular filtration rate remained essentially unchanged at 254 (SEM 3) ml/20 min, 568 (5) ml/min/1.73 m2, and 110 (2) ml/min/1.73 m2 respectively. From similar basal values the infusion of somatostatin led to a rapid decrease in all three variables. After 120 minutes of infusion of somatostatin urinary volume, renal plasma flow, and glomerular filtration rate were reduced to 148 (17) ml/20 min (p less than 0.01), 422 (7) ml/min/1.73 m2 (p less than 0.001), and 93 (3) ml/min/1.73 m2 (p less than 0.05) respectively. This effect on renal function should be borne in mind whenever somatostatin is used.


Prediction of Drug-Drug Interactions with Crizotinib as the CYP3A Substrate Using a Physiologically Based Pharmacokinetic Model.
An orally available multiple tyrosine kinase inhibitor, crizotinib (Xalkori), is a CYP3A substrate, moderate time-dependent inhibitor, and weak inducer. The main objectives of the present study were to: 1) develop and refine a physiologically based pharmacokinetic (PBPK) model of crizotinib on the basis of clinical single- and multiple-dose results, 2) verify the crizotinib PBPK model from crizotinib single-dose drug-drug interaction (DDI) results with multiple-dose coadministration of ketoconazole or rifampin, and 3) apply the crizotinib PBPK model to predict crizotinib multiple-dose DDI outcomes. We also focused on gaining insights into the underlying mechanisms mediating crizotinib DDIs using a dynamic PBPK model, the Simcyp population-based simulator. First, PBPK model-predicted crizotinib exposures adequately matched clinically observed results in the single- and multiple-dose studies. Second, the model-predicted crizotinib exposures sufficiently matched clinically observed results in the crizotinib single-dose DDI studies with ketoconazole or rifampin, resulting in the reasonably predicted fold-increases in crizotinib exposures. Finally, the predicted fold-increases in crizotinib exposures in the multiple-dose DDI studies were roughly comparable to those in the single-dose DDI studies, suggesting that the effects of crizotinib CYP3A time-dependent inhibition (net inhibition) on the multiple-dose DDI outcomes would be negligible. Therefore, crizotinib dose-adjustment in the multiple-dose DDI studies could be made on the basis of currently available single-dose results. Overall, we believe that the crizotinib PBPK model developed, refined, and verified in the present study would adequately predict crizotinib oral exposures in other clinical studies, such as DDIs with weak/moderate CYP3A inhibitors/inducers and drug-disease interactions in patients with hepatic or renal impairment.


Effect of human carbonic anhydrase II on the activity of the human electrogenic Na/HCO3 cotransporter NBCe1-A in Xenopus oocytes.
Others report that carbonic anhydrase II (CA II) binds to the C termini of the anion exchanger AE1 and the electrogenic Na/HCO3 cotransporter NBCe1-A, enhancing transport. After injecting oocytes with NBCe1-A cRNA (Day 0), we measured NBC current (I(NBC)) by two-electrode voltage clamp (Day 3), injected CA II protein + Tris or just Tris (Day 3), measured I(NBC) or the initial rate at which the intracellular pH fell (dpH(i)/dt) upon applying 5% CO2 (Day 4), exposed oocytes to the permeant CA inhibitor ethoxzolamide (EZA), and measured I(NBC) or dpH(i)/dt (Day 4). Because dpH(i)/dt was greater in CA II than Tris oocytes, and EZA eliminated the difference, injected CA II was functional. I(NBC) slope conductance was unaffected by injecting CA II. Moreover, EZA had identical effects in CA II versus Tris oocytes. Thus, injected CA II does not enhance NBC activity. In a second protocol, we made a fusion protein with enhanced green fluorescent protein (EGFP) at the 5' end of NBCe1-A and CA II at the 3' end (EGFP-e1-CAII). We measured I(NBC) or dpH(i)/dt (days 3-4), exposed oocytes to EZA, and measured I(NBC) or dpH(i)/dt (Day 3-4). dpH(i)/dt was greater in oocytes expressing EGFP-e1-CA II versus EGFP-e1, and EZA eliminated the difference. Thus, fused CA II was functional. Slope conductances of EGFP-e1-CAII versus EGFP-e1 oocytes were indistinguishable, and EZA had no effect. Thus, even when fused to NBCe1-A, CA II does not enhance NBCe1-A activity.


Effect of artemisinin on neuropathic pain mediated by P2X4 receptor in dorsal root ganglia.
Neuropathic pain is a type of chronic pain caused by nervous system damage and dysfunction. The pathogenesis of chronic pain is complicated, and there are no effective therapies for neuropathic pain. Studies show that the P2X4 receptor expressed in the satellite glial cells (SGCs) of dorsal root ganglia (DRG) is related to neuropathic pain. Artemisinin is a monomeric component extracted from traditional Chinese medicine and has a variety of important pharmacological effects and potential applications. This study observed the effect of artemisinin on neuropathic pain and delineated its possible mechanism. The chronic constriction injury (CCI) rat model was used in this study. The results demonstrated that artemisinin relieved pain behaviors in the CCI rats, inhibited the expression of P2X4 receptor in the DRG, and decreased the ATP-activated currents in HEK293 cells transfected with P2X4 plasmid. Dual-labeling immunofluorescence showed that the coexpression of P2X4 receptor and glial fibrillary acidic protein (GFAP) in the DRG of CCI rats was increased compared to control rats. After CCI rats were treated with artemisinin, the coexpression of P2X4 receptor and GFAP in the DRG was significantly decreased compared to the CCI group. This finding suggested that artemisinin could inhibit the nociceptive transmission mediated by P2X4 receptor in the DRG SGCs and thus relieve pain behaviors in the CCI rats.


The influence of a short-term gluten-free diet on the human gut microbiome.
A gluten-free diet (GFD) is the most commonly adopted special diet worldwide. It is an effective treatment for coeliac disease and is also often followed by individuals to alleviate gastrointestinal complaints. It is known there is an important link between diet and the gut microbiome, but it is largely unknown how a switch to a GFD affects the human gut microbiome. We studied changes in the gut microbiomes of 21 healthy volunteers who followed a GFD for four weeks. We collected nine stool samples from each participant: one at baseline, four during the GFD period, and four when they returned to their habitual diet (HD), making a total of 189 samples. We determined microbiome profiles using 16S rRNA sequencing and then processed the samples for taxonomic and imputed functional composition. Additionally, in all 189 samples, six gut health-related biomarkers were measured. Inter-individual variation in the gut microbiota remained stable during this short-term GFD intervention. A number of taxon-specific differences were seen during the GFD: the most striking shift was seen for the family Veillonellaceae (class Clostridia), which was significantly reduced during the intervention (p = 2.81 × 10(-05)). Seven other taxa also showed significant changes; the majority of them are known to play a role in starch metabolism. We saw stronger differences in pathway activities: 21 predicted pathway activity scores showed significant association to the change in diet. We observed strong relations between the predicted activity of pathways and biomarker measurements. A GFD changes the gut microbiome composition and alters the activity of microbial pathways.


Three-component coupling based on the "cation pool" method.
Sequential one-pot three-component coupling reactions have been developed based on the "cation pool" method. An N-acyliminium ion generated by the "cation pool" method adds to an electron-rich carbon-carbon double bond, such as enamine derivatives and vinyl sulfides, to form the second "cation pool". The addition of nucleophiles such as allylsilanes, enol silyl ethers, Grignard reagents, and organoaluminum compounds led to the formation of the corresponding three-component coupling products.


Too Much Too Late? Chemotherapy Administration at the End of Life: A Retrospective Observational Study.
Cancer treatment for those nearing death has become increasingly aggressive over time despite evidence that less aggressive approaches are associated with better quality of life and sometimes longer survival. Chemotherapy administration in the last 14 days of life is one of the proposed benchmarks for quality of cancer care. The purpose of our study is to evaluate factors associated with aggressive cancer treatment in patients who died within 2 weeks of receiving chemotherapy. This retrospective cohort study evaluated adult patients who died between 1 February 2018 and 1 March 2019 after receiving cancer treatment in the preceding 14 days at the Prisma Health Cancer Institute. This project was approved by our institutional review board. Data was obtained by review of electronic medical records and analyzed using commercial software. We identified 92 patients who met inclusion criteria for the study. Of those who were staged, 57% had metastatic disease. A majority received treatments with only palliative intent (54%). These patients overwhelmingly died in the hospital (62%). Few had documented advanced directives (28%) or dedicated palliative care for longer than 1 week (28%). Overall, this cohort reflects a rate of 11.7% of patients who received cancer treatment during the study time period. Patients receiving aggressive cancer treatment at the end of life elucidate significant gaps in quality cancer care, particularly the early involvement of dedicated palliative care. Systematic review helped identify multiple gaps and assisted in implementing interventions to improve this outcome.


Serum alkaline phosphatase reflects post-Fontan hemodynamics in children.
Although survivors of Fontan palliation for a single ventricle are known to have lower cardiac index than patients with two-ventricle surgical reconstructions, it is unclear whether two frequently observed sequelae, short stature and protein-losing enteropathy (PLE), have hemodynamic origins. A serum marker that reflects hemodynamic status would be a tremendous asset in the long-term management of children with these sequelae. The authors recently noted severely reduced total alkaline phosphatase (TALP) levels in two children with early-onset PLE after Fontan operations, both of whom had low cardiac output at cardiac catheterization. Catheter-based or surgical interventions that rapidly increased cardiac output in these two patients resulted not only in relief of PLE but also in a prompt TALP rise. To examine whether the apparent correlation of low TALP with impaired cardiac output also is seen in Fontan patients without PLE, this study retrospectively examined the TALP data from two other Fontan patients who underwent cardiac catheterization specifically to assess the potential benefit of vasodilator therapy. The TALP levels were abnormally low in both cases but increased after up-titration of angiotensin-converting enzyme inhibition. Serum TALP activity, an indicator of osteoblastic function particularly in pre-adolescence, may be a marker of low cardiac output after a Fontan operation.


Complete Genome Sequence of Two Rift Valley Fever Virus Strains Isolated from Outbreaks in Saudi Arabia (2000) and Kenya (2006 to 2007).
The complete genome sequence, including the untranslated regions, of two Rift Valley fever virus (RVFV) strains isolated from mosquitoes that were collected from disease outbreaks in Saudi Arabia (2001) and Kenya (2006 to 2007) were sequenced using next-generation sequencing technology.


An algorithm for 353 odor detection thresholds in humans.
One hundred and ninety three odor detection thresholds, ODTs, obtained by Nagata using the Japanese triangular bag method can be correlated as log (1/ODT) by a linear equation with R(2) = 0.748 and a standard deviation, SD, of 0.830 log units; the latter may be compared with our estimate of 0.66 log units for the self-consistency of Nagata's data. Aldehydes, acids, unsaturated esters, and mercaptans were included in the equation through indicator variables that took into account the higher potency of these compounds. The ODTs obtained by Cometto-Muñiz and Cain, by Cometto-Muñiz and Abraham, and by Hellman and Small could be put on the same scale as those of Nagata to yield a linear equation for 353 ODTs with R(2) = 0.759 and SD = 0.819 log units. The compound descriptors are available for several thousand compounds, and can be calculated from structure, so that further ODT values on the Nagata scale can be predicted for a host of volatile or semivolatile compounds.


Pre-concentration and separation of bacteria by volume coupling electrophoresis on supercritical water-etched fused silica capillary with two segments of different internal diameters and inner surface roughnesses.
The transient isotachophoretic stacking and sweeping was used for the on-line large-volume sample pre-concentration of bacteria, Escherichia coli and Staphylococcus aureus cells (methicillin-susceptible or methicillin-resistant), in the initial stage of micellar electrokinetic chromatography using a non-ionogenic surfactant or of capillary electrophoresis, respectively. These procedures were employed in single-piece fused silica capillary etched with supercritical water with two different internal diameter segments featuring different inner surface roughness. Large volumes (maximum 2.8 μL) of the high conductivity sample matrices, physiological saline solution, urine or blood (with purification step), spiked with examined cells were injected into the wider end of a capillary with an inlet inner diameter 195 μm. This novel on-line combination of preconcentration strategies for cells produced an up to 680-fold increase in sensitivity for E. coli or S. aureus cells. The average calculated resolutions, R, for five selected methicillin-susceptible or methicillin-resistant strains were found to be 6.3 for the agar-cultivated and 14.9 for the blood-incubated cells. A low number of bacteria similar to those in clinical samples were also tested. The modified surface roughness step helped to significantly narrow the cell zones and to increase resolution. The migration velocities of E. coli agar-cultivated and blood-incubated cells were approximately the same as those of S. aureus, probably due to the minimal differences in their surface properties. This procedure, on-line pre-concentration and separation of bacteria, is rapid and provides good reproducibility and repeatability.


Conjugated 4-methoxybipyrrole thiophene azomethines: synthesis, opto-electronic properties, and crystallographic characterization.
In the search of functional materials with improved electrochromic properties, thiophenes and asymmetric bipyrroles have been conjugated with azomethine units. 4-Methoxy-2,2'-bipyrroles 3-6 were first synthesized by a general route from 4-hydroxyproline and converted subsequently to dialdehydes 8-15, which underwent condensations with different aminothiophenes to provide azomethine conjugates 14-18 and 20-22. The crystallization and X-ray analysis of 20 showed the heterocycles and azomethine bonds were all co-planar with the heterocycles adopting an anti-parallel arrangement. These configurations result in extended conjugation and enhanced opto-electronic properties of the azomethines. Oxidation potential (E(pa)) was tailored by modification of the substitution pattern of the terminal thiophenes and central pyrroles of the azomethines. The combined low E(pa) and extended azomethine degree of conjugation resulted in stark color transitions occurring between their neutral and oxidized states. Reversible color formation was induced both electrochemically and by doping/de-doping with trifluoroacetic acid/triethylamine.


Aberrant expression of cell-free nucleosomes in dermatomyositis/polymyositis.
Nucleosomes are typically located intracellularly, and extracellular levels of nucleosomes indicated the degree of cell death. We postulated aberrant nucleosomes expression in dermatomyositis (DM) and polymyositis (PM). To assess the aberrant expression of circulating nucleosomes in DM and polymyositis. 76 consecutive DM and PM patients from 1 September 2017 to 31 October 2018 were enrolled in this study, in addition to 20 healthy controls. The levels of circulating nucleosomes, with 16 kinds of detectable myositis-specific antibodies (MSAs) were detected in IIMs patients using enzyme-linked immunosorbent assay kit (ELISA). Receiver operating characteristic (ROC) curve analysis was performed for evaluating the ability of this candidate marker for detecting DM/PM. The results showed that the levels of circulating nucleosomes in DM/PM patients were significantly higher than that in normal individuals. Specifically, elevated levels of nucleosomes were associated with MDA5 Ab, ARS, and TIF1γAb. In addition, elevated levels of circulating nucleosomes correlated with skin eruption. This study has evidenced nucleosomes as a potential new biomarker of DM/PM. Aberrant nucleosomes expression occurs in myositis patients and the difference in nucleosomes expression between patients with and without skin eruption is statistically significant. A unique expression profile of elevated serum nucleosomes was detected in DM/PM-MDA5 Ab(+), ASS, and TIF1γAb(+).


Nasal inhalation of l-menthol reduces respiratory discomfort associated with loaded breathing.
To test the hypothesis that stimulation of cold receptors in the upper airway may alleviate the sensation of respiratory discomfort, we investigated the effects of nasal inhalation of l-menthol (a specific stimulant of cold receptors) on the respiratory sensation and ventilation during the loaded breathing in 11 normal subjects. Subjects were asked to rate their sensation of respiratory discomfort using a visual analog scale (VAS) while breathing on a device with a flow-resistive load (180 cm H2O/L/s) or with an elastic load (75.5 cm H2O/L). The effects of inhalation of l-menthol on ventilation and respiratory sensation were evaluated by comparing the steady-state values of ventilatory variables and VAS scores obtained before, during, and after l-menthol inhalation. In 8 of 11 subjects inhalation of strawberry-flavored air instead of l-menthol was performed during loaded breathing. Both during the flow-resistive loading and the elastic loading, inhalation of l-menthol caused a significant reduction in sensation of respiratory discomfort (flow-resistive loading: 62 +/- 14 [mean +/- SD] VAS units before inhalation versus 36 +/- 16 during inhalation, p < 0.01; elastic loading: 68 +/- 13 before inhalation versus 55 +/- 17 during inhalation, p < 0.01) without a significant change in breathing pattern and ventilation. Comparison of the effects between the flow-resistive loading and the elastic loading also revealed that the reduction in VAS score was more during the flow-resistive loading than during the elastic loading (p < 0.01). Inhalation of strawberry-flavored air caused neither changes in VAS score nor changes in breathing pattern and ventilation, indicating that olfaction is not a contributing factor in the relief of respiratory discomfort. We concluded that stimulation of cold receptors in the upper airway with nasal inhalation of l-menthol reduces the sensation of respiratory discomfort associated with loaded breathing. This effect is more effective during the flow-resistive loading than during the elastic loading.


Quality of life of myasthenia gravis patients.
To investigate the impact of myasthenia gravis (MG) on the quality of life (QOL) of MG patients. QOL was assessed with SF-36 questionnaire. Thirty-one patients participating in the present study, 74.2% female, with an average age of 44.9 years old. From the SF-36 questionnaire, emotional well being had the lowest score while other components were in average or high range. Ocular and mild generalized MG had better physical functioning than moderate generalized MG With treatment, those who had no or minimal symptoms had better QOL in both physical and mental aspects. Immunosuppressant was not associated with poor QOL. QOL of Thai MG patients is better than Westerners. However, MG still has significant impact to both physical and mental aspects. More emphasis is needed for mental aspects. The degree of disease control is very important in QOL and the use of immunosuppressant does not impair QOL.


Personalized Medicine for Chronic Respiratory Infectious Diseases: Tuberculosis, Nontuberculous Mycobacterial Pulmonary Diseases, and Chronic Pulmonary Aspergillosis.
Chronic respiratory infectious diseases are causing high rates of morbidity and mortality worldwide. Tuberculosis, a major cause of chronic pulmonary infection, is currently responsible for approximately 1.5 million deaths per year. Although important advances in the fight against tuberculosis have been made, the progress towards eradication of this disease is being challenged by the dramatic increase in multidrug-resistant bacilli. Nontuberculous mycobacteria causing pulmonary disease and chronic pulmonary aspergillosis are emerging infectious diseases. In contrast to other infectious diseases, chronic respiratory infections share the trait of having highly variable treatment outcomes despite longstanding antimicrobial therapy. Recent scientific progress indicates that medicine is presently at a transition stage from programmatic to personalized management. We explain current state-of-the-art management concepts of chronic pulmonary infectious diseases as well as the underlying methods for therapeutic decisions and their implications for personalized medicine. Furthermore, we describe promising biomarkers and techniques with the potential to serve future individual treatment concepts in this field of difficult-to-treat patients. These include candidate markers to improve individual risk assessment for disease development, the design of tailor-made drug therapy regimens, and individualized biomarker-guided therapy duration to achieve relapse-free cure. In addition, the use of therapeutic drug monitoring to reach optimal drug dosing with the smallest rate of adverse events as well as candidate agents for future host-directed therapies are described. Taken together, personalized medicine will provide opportunities to substantially improve the management and treatment outcome of difficult-to-treat patients with chronic respiratory infections.


Cascade Detrifluoroacetylation, C-S Bond Cleavage, and SN2' Reaction of α,α-Difluorinated Gem-Diols with MBH Esters.
A new SN2' reaction type of Morita-Baylis-Hillman (MBH) ester with sulfonyl anion, generated in situ via detrifluoroacetylation as a nucleophile is developed. Experimental results and DFT calculations disclose that the reaction proceeds via C-C bond cleavage to generate a PhSO2CF2 anion, C-S bond cleavage to generate a sulfonyl anion with the release of CF2 carbene, and an SN2' reaction with the MBH ester. The reaction features operational simplicity, wide substrate scope, high yields, and excellent stereoselectivity, which represents a new reaction mode of fluorinated gem-diols and also provides an efficient way to obtain β,γ-unsaturated sulfones.


Hypertrabecular aspect of left ventricular myocardium: a possible complication of congenital hypothyroidism in a preterm infant.
We report a case of hypertrabeculated left ventricular myocardium associated with congenital hypothyroidism in a preterm infant. The myocardical anomalies and long QT interval, absent at birth, appeared simultaneously to abnormal thyroid hormones and progressively improved until complete recovery during Levo-Thyroxine treatment. We speculate that thyroid dysfunction could be the potential cause of transient hypertrabecular aspect of the left ventricle.


Involvement of histidines 11, 15 and 19 in the binding of zinc to the fusogenic H5WYG peptide.
The histidine-rich GLFHAIAHFIHGGWHGLIHGWYG peptide (H5WYG) coordinates a Zn2+ ion and forms a stable peptide-metal complex promoting membrane fusion at physiologic pH. In our previous article titled 'Histidine-rich peptide: evidence for a single zinc-binding site on H5WYG peptide that promotes membrane fusion at neutral pH' in Journal of Mass Spectrometry (2009, 44, 81-89), tandem mass spectrometry experiments have provided evidence for the binding of a single Zn2+ ion to H5WYG and suggested that this binding is shared between H11, H19 and probably H15 residues. To clarify the involvement of these histidine residues in the binding to the Zn2+ ion and especially to remove the doubt about the implication of the H15 residue, here we have used three H5WYG mutants termed H5WYGH11A, H5WYGH15A and H5WYGH19A, whose H11, H15 and H19 residues were replaced with an alanine residue. The novelty introduced by these new tandem mass spectrometry experiments performed with the mutants is the demonstration that H15 is involved in the binding of the single Zn2+ ion and that it may even favour the setting of another Zn2+ ion. Thus, the three histidines H11, H15 and H19 could lead to a specific structuring of H5WYG that can promote membrane fusion upon the binding of zinc.


The uptake of oestrone from the lumen of the isolated perfused rat gut.
1. In the isolated perfused rat gut oestrone was not taken up from the perfusate but was rapidly taken up from the gut lumen when administered in dimethyl sulphoxide or in 10% acetone in water. 2. Uptake from corn oil was much slower and the rate was concentration-dependent. 3. When given in dimethyl sulphoxide or in aqueous acetone, the residual oestrone in the gut lumen was largely unchanged, with only about 10% being present as the glucuronide. Of the oestrone in the gut perfusate, some 40% was glucuronidated. 4. No evidence was obtained for any reduction or hydroxylation, or for any sulphation, during uptake of oestrone by the gut. 5. No secretion of oestrone or its metabolites into lymph could be detected.


[DNA ploidy of testicular germ cell tumors in childhood; difference from adult testicular tumors].
It is well known that there are various differences in the biological characteristics and clinical behavior between prepubertal testicular germ cell tumors and adult ones. We analyzed the nuclear DNA ploidy of testicular tumors in childhood using DNA flow cytometry for clarifying those biological features and shedding some insights in the pathogenesis of testicular germ cell tumors. Formalin-fixed, paraffin-embedded specimens of primary tumors taken from 9 boys with histological evidence of yolk sac tumors and 8 with prepubertal teratoma treated in our clinic were used for flow cytometry analysis with some modification of the Hedley's technique. The results were compared with those of adult testicular tumors which we previously reported. All specimens in children showed "DNA euploid"; DNA diploid in all teratomas and 6 yolk sac tumors, DNA tetraploid in other 3 yolk sac tumors. Neither distinct DNA aneuploidy nor DNA heterogeneity were detected in children. Our previous study proved that the vast majority of adult testicular tumors contain DNA aneuploid stemlines. Although prepubertal yolk sac tumor and teratoma are histologically identical with those in adults, this study apparently reveal the different DNA stemline ploidy in prepubertal testicular tumors compared with that in adult ones. It has been known that carcinoma in situ (CIS) of the testis is a precursor of adult testicular germ cell tumors and the CIS cells in precancerous state already shows aneuploid DNA histogram patterns. Moreover, CIS has never been observed in children. The current results are in agreement with the hypothesis that the pathogenesis of prepubertal testicular tumor is different from that of adult ones.(ABSTRACT TRUNCATED AT 250 WORDS)


Analysis of the functional domains of herpes simplex virus type 1 immediate-early polypeptide Vmw110.
At the onset of infection by herpes simplex virus type 1 (HSV-1) in tissue culture, five immediate-early (IE) genes are expressed. At least four of the IE gene products have some role in the transcriptional regulation of later classes of viral genes. This study concerns the product of IE gene 1, Vmw110. Several laboratories have shown that a cloned copy of IE gene 1 can stimulate gene expression in trans in transfection experiments; this transactivation can occur either with Vmw110 by itself or in a strongly synergistic fashion with the product of IE gene 3, Vmw175. As an approach to study the mechanism of this effect, a large number of in-frame insertion mutations in the Vmw110 coding region have been constructed. The effect of the insertions on the ability of Vmw110 to activate transcription in the presence of Vmw175 has been described. This report concerns the effect of the insertions on the ability of Vmw110 to activate gene expression in the absence of Vmw175. In addition, a family of in-frame deletion mutations has been constructed and tested in transfection and immunofluorescence assays. The results show (1) that mutations in different domains of the Vmw110 polypeptide can have different effects on function in the presence or absence of Vmw175; (2) that mutations can affect the pattern of immunofluorescent intranuclear staining of Vmw110; and (3) that deletions in the region of a particular highly basic region of the polypeptide result in failure of Vmw110 to be transported into the nucleus.


Transmission dynamics and control of Ebola virus disease outbreak in Nigeria, July to September 2014.
We analyse up-to-date epidemiological data of the Ebola virus disease outbreak in Nigeria as of 1 October 2014 in order to estimate the case fatality rate, the proportion of healthcare workers infected and the transmission tree. We also model the impact of control interventions on the size of the epidemic. Results indicate that Nigeria's quick and forceful implementation of control interventions was determinant in controlling the outbreak rapidly and avoiding a far worse scenario in this country.


Regions in the carboxy terminus of alpha-bENaC involved in gating and functional effects of actin.
Gating differences occur between the alpha-subunits of the bovine and rat clones of an amiloride-sensitive epithelial Na+ channel (ENaC). Deletion of the carboxy terminus of bovine alpha-ENaC (alpha-bENaC) at R567 converted the gating properties to that of rat alpha-ENaC (alpha-rENaC). The equivalent truncation in alpha-rENaC was without effect on the gating of the rat homologue. The addition of actin to ENaC channels composed of either alpha-rENaC or alpha-bENaC alone produced a twofold reduction in conductance and an increase in open probability. Neither alpha-rENaC (R613X) nor alpha-bENaC (R567X) was responsive to actin. Using a chimera consisting of alpha-rENaC1-615 and alpha-bENaC570-650, we examined several different carboxy-terminal truncation mutants plus and minus actin. When incorporated into planar bilayers, the gating pattern of this construct was identical to wild-type (wt) alpha-bENaC. Premature stop mutations proximal to E685X produced channels with gating patterns like alpha-rENaC. Actin had no effect on the E631X truncation, whereas more distal truncations all interacted with actin, as did wt alpha-bENaC. Key findings were confirmed using channels expressed in Xenopus oocytes and studied by cell-attached patch-clamp recording. Our results suggest that the site of actin regulation at the carboxy terminus of the chimera is located between residues 631 and 644.


[Development of conjunctival hyperemia with the use of a fixed combination of latanoprost/timolol: systematic review and meta-analysis of clinical trials].
To asses the association of conjunctival hyperemia with the use of a fixed combination of latanoprost/timolol, through a systematic review and meta-analysis of clinical trials in patients with glaucoma. A systematic review of published clinical trials of latanoprost/timolol and other competitors was conducted in Medline, Embasse and Cochrane Controlled Clinical Trials Register, between 2000 and 2007. Statistical analysis included calculation of the odds ratio (OR) with its 95% confidence interval (CI) using the fixed effects model of Mantel-Haenszel and the random effects model of Der Simonian and Laird. To assess the heterogeneity between trials the Cochrane Q test and the I(2) rate were calculated. The conjunctival hyperemia rates obtained were compared with the Chi-square test. A total of 8 clinical trials comparing latanoprost/timolol fixed combination with different therapeutic options were found. As trial heterogeneity was moderate (Q: 14.64; df=7; p=0.041; I(2)= 52.2%) a random effects model was used. The final OR was 0.47 (CI 95%: 0.24-0.90); p = 0.024. The total conjunctival hyperemia incidence was 2.9% in the latanoprost/timolol group and 7.0% for the competitors (p<0.0001). The use of a fixed combination of latanoprost/timolol is associated with a significant reduction (53%; CI 95%: 10%-76%) in the development of conjunctival hyperemia against the other compared options for the treatment of glaucoma.


Cost-effectiveness analysis of hernioplasties before and after the implementation of the ACERTO project.
to compare hospital costs and clinical outcomes in inguinal and incisional hernioplasty before and after implementation of the ACERTO project in a university hospital. retrospective study of 492 patients undergoing either inguinal hernioplasty (n=315) or incisional hernioplasty (n=177). The investigation involved two phases: between January 2002 and December 2005, encompassing cases admitted before the implementation of the ACERTO protocol (PRE-ACERTO period), and the other phase, with cases operated between January 2006 and December 2011, after the implementation of the protocol (ACERTO period). The main outcome variable was the comparison of the mean hospital costs between the two periods. As secondary endpoints, we analyzed the length of stay, the surgical site infection rate and mortality. We used the cost method suggested by Public Sector Cost Information System. surgical site infection was higher (p = 0.039) in the first phase of the study for both inguinal hernia operations (2 (1.6%) versus 0 (0%) cases) and incisional hernioplasty (5 (7.6%) versus 3 (2.7%) cases). The length of stay decreased one day after the implementation of the ACERTO protocol (p=0.005). There was a reduction in costs per patient from R$ 4,328.58 per patient in the first phase to R$ 2,885.72 in the second phase (66.7% reduction). there was a reduction in infectious morbidity, length of stay and hospital costs in hernioplasty after the implementation of the ACERTO protocol.


Mobile Technology Improves Adherence to Cardiac Rehabilitation: A Propensity Score-Matched Study.
Background Despite its established effectiveness, adherence to cardiac rehabilitation remains suboptimal. The purpose of our study is to examine whether mobile technology improves adherence to cardiac rehabilitation and other outcomes. Methods and Results We identified all enrollees of the cardiac rehabilitation program at Boston Medical Center from 2016 to 2019 (n=830). Some enrollees used a mobile technology application that provided a customized list of educational content in a progressive manner, used the patient's smartphone accelerometer to provide daily step counts, and served as a 2-way messaging system between the patient and program staff. Adherence to cardiac rehabilitation was defined as the number of attended sessions and completion of the program. Enrollees had a mean age of 59 years; 32% were women, and 42% were Black. Using 3:1 propensity matching for age, sex, race/ethnicity, education, smoking status, transportation time, diagnosis, and baseline depression survey score, we evaluated change in exercise capacity, weight, functional capacity, and nutrition scores. Those in the mobile technology group (n=114) attended a higher number of prescribed sessions (mean 28 versus 22; relative risk, 1.17; 95% CI, 1.04-1.32; P=0.009), were 1.8 times more likely to complete the cardiac rehabilitation program (P=0.01), and had a slightly greater weight loss (pounds) following rehabilitation (-1.71; 95% CI, -0.30 to -3.11; P=0.02) as compared with those in the standard group (n=213); other outcomes were similar between the groups. Conclusions In a propensity-matched, racially diverse population, we found that adjunctive use of mobile technology is significantly associated with improved adherence to cardiac rehabilitation and number of attended sessions.


Immediate vs. delayed treatment of group A beta-hemolytic streptococcal pharyngitis with penicillin V.
Three hundred six children with probable Group A beta-hemolytic streptococcal pharyngitis were enrolled in a randomized double blind trial to compare the effects of immediate vs. delayed treatment with oral penicillin V. Among the 229 culture-positive patients, 111 were randomly assigned to receive penicillin V immediately and 118 to receive a placebo for 48 to 52 hours followed by penicillin V. Patients were evaluated clinically for 48 to 52 hours following initiation of treatment. The Streptozyme test was used to measure acute to convalescent antibody titer. Both regimens resulted in a greater than 92% cure rate. Early treatment was associated with significantly fewer and milder signs and symptoms on Day 3 and a significantly lower rise in the antibody titer. On the other hand we found 8 (7%) relapses and 18 (16%) early and 14 (13%) late recurrences in this group; all were significantly higher than the corresponding numbers of 2 (2%), 6 (5%) and 4 (3%), respectively, in the late treatment group. This study shows the beneficial effect of early treatment with penicillin V on the clinical course of Group A beta-hemolytic streptococcal pharyngitis. This study also shows that delayed penicillin treatment may be associated with a lower incidence of subsequent Group A beta-hemolytic streptococcal pharyngitis.


Mucosal regulatory T cells in airway hyperresponsiveness.
Interest in regulatory T cells (Treg) and their role in immune regulation has grown almost exponentially over the last 10 years, though the notion of a suppressive population of T cells has been in existence since the early 1970s. Recent reports have highlighted the potential role of populations of Treg in control of T-cell-mediated inflammation in tissues, including the lung. In particular, there is now evidence to suggest that Treg form a fundamental part of the regulatory axis operating within the respiratory mucosa and that the number of Treg recruited to the airways may be crucial for the inhibition of airways hyperresponsiveness associated with exacerbations of asthma. A discussion of these concepts is the focus of this chapter.


Wash-off potential of urban use insecticides on concrete surfaces.
Contamination of surface aquatic systems by insecticides is an emerging concern in urban watersheds, but sources of contamination are poorly understood, hindering development of regulatory or mitigation strategies. Hardscapes such as concrete surfaces are considered an important facilitator for pesticide runoff following applications around homes. However, pesticide behavior on concrete has seldom been studied, and standardized evaluation methods are nonexistent. In the present study, a simple batch method for measuring pesticide wash-off potential from concrete surfaces was developed, and the dependence of washable pesticide residues was evaluated on pesticide types, formulations, time exposed to outdoor conditions, and number of washing cycles. After application to concrete, the washable fraction of four pyrethroids (bifenthrin, permethrin, cyfluthrin, and cyhalothrin) and fipronil rapidly decreased, with half-lives < or =3 d, likely due to irreversible retention in micropores below the concrete surface. The initial fast decrease was followed by a much slower declining phase with half-lives ranging from one week to two months, and detectable residues were still found in the wash-off solution for most treatments after 112 d. The slow decrease may be attributed to a fraction of pesticides being isolated from degradation or volatilization after retention below the concrete surface. Wash-off potential was consistently higher for solid formulations than for liquid formulations, implying an increased runoff contamination risk for granular and powder formulations. Trace levels of pyrethroids were detected in the wash-off solution even after 14 washing-drying cycles over 42 d under outdoor conditions. Results from the present study suggest that pesticide residues remain on concrete and are available for contaminating runoff for a prolonged time. Mechanisms for the long persistence were not clearly known from the present study and merit further investigation.


3D-QSAR CoMFA study of benzoxazepine derivatives as mGluR5 positive allosteric modulators.
Positive allosteric modulation of the metabotropic glutamate receptor subtype 5 was studied by conducting a comparative molecular field analysis on 118 benzoxazepine derivatives. The model with the best predictive ability retained significant cross-validated correlation coefficients of q(2) = 0.58 (r(2) = 0.81) yielding a standard error of 0.20 in pEC(50) for this class of compounds. The subsequent contour maps highlight the structural features pertinent to the bioactivity values of benzoxazepines.


Distribution of iron-containing superoxide dismutase in vascular plants.
Superoxide dismutases (EC 220.127.116.11) in vascular plants representing different evolutionary levels were characterized using polyacrylamide gel electrophoresis. The three forms of the enzyme were distinguished from each other based on the following criteria: a) the Cu-Zn enzyme is sensitive to cyanide wherease the Fe and Mn enzymes are not; and b) the Cu-Zn and Fe enzymes are inhibited by H(2)O(2) whereas the Mn enzyme is H(2)O(2)-resistant. Of the 43 plant families investigated, the Fe-containing superoxide dismutase was found in three families: Gingkoaceae, Nymphaceae, and Cruciferae.


Brunfelsia australis (Yesterday, Today, and Tomorrow tree) and Solanum poisoning in a dog.
A 2.5 yr old female beagle presented for acute abdominal pain and vomiting after consuming limited offerings of green potato skins. Progressive complications associated with suspected ingestion of a higher potency toxin followed within 5 hr. Subsequent investigations revealed a significant ingestion of an Australian shrub commonly called a "Yesterday, Today, and Tomorrow" tree (Brunfelsia australis). The toxic principle for this emerging toxicity is referred to as "strychnine-like" and is potentially lethal with gastrointestinal, central nervous system, and cardiac pathology. This plant is currently being aggressively promoted by United States nurserymen for its dramatic tri-colored blooms and drought resistance.


Sex Differences in Serum C-Reactive Protein Course after Total Hip Arthroplasty.
Gender-specific medicine has become an important part in investigating the course of various diseases. C-reactive protein (CRP) is used as an inflammatory marker for detecting inflammations and even infections after total hip arthroplasty (THA). The general course of CRP after THA is well known, but there is controversy about its association with sex. Therefore, we aimed to investigate if there is an influence of sex on the CRP after THA in the first 10 days after operation in a complication-free course in male and female patients and to re-evaluate the specific postoperative CRP course with its maximum on the second to third postoperative days. We retrospectively reviewed patients who had been treated with THA due to primary osteoarthritis through the same approach using an equal model of a cementless stem and a cup and complication-free between 2013 and 2016. Patients with active inflammation, rheumatoid arthritis, secondary arthrosis, active cancer disease, and documented postoperative complications were not included. The CRP values before THA and up to 10 days after THA were recorded and tested for sex discrepancy. Factor analyses were performed, and CRP values were adjusted for confounders (age, operation time, diabetes mellitus, and body mass index [BMI]). A total of 1,255 patients (728 women and 527 men) were finally analyzed. Men were younger and had a longer operation time and a higher BMI compared to women. The prevalence of overweight was higher in men, while obesity (BMI > 40 kg/m2), diabetes mellitus, renal failure, and American Society of Anaesthesiologists status showed no significant difference between men and women. Men had significantly higher CRP values than women between the 2nd and the 7th postoperative days, with the largest difference on the 4th postoperative day (men, 130.48 mg/L; women, 87.26 mg/L; p = 0.018). Based on the results of more precise sex-specific evaluation of the postoperative CRP course after THA, the present study showed for the first time that there was a gender discrepancy in the CRP course after complication-free THA in the first 7 postoperative days. Furthermore, this study confirmed the postoperative CRP course with its maximum on the third postoperative day.


A Single-Carbon Stable Isotope Ratio Model Prediction Equation Can Estimate Self-Reported Added Sugars Intake in an Adult Population Living in Southwest Virginia.
The δ13C value of blood is a novel proposed biomarker of added sugars (AS) intake. AS prediction equations using either a single- (δ13C) or dual-isotope model (δ13C and δ15N) were previously developed in an adult population with high AS intake living in southwest Virginia (reference group). The purpose of this investigation was to test the δ13C single- and δ13C and δ15N dual-isotope prediction equations for AS intake in adults with a lower mean AS intake and different demographic characteristics (test group). The blood samples for the reference (n = 257 for single-isotope, n = 115 for dual-isotope) and test groups (n = 56) were analyzed for δ13C and δ15N values using natural abundance stable isotope mass spectrometry and were compared to reported dietary AS intake. When the δ13C single-isotope equation was applied to the test group, predicted AS intake was not significantly different from reported AS intake (mean difference ± standard error = -3.6 ± 5.5 g, Z = -0.55, p = 0.51). When testing the dual-isotope equation, predicted AS was different from reported AS intake (mean difference ± SEM = 13.0 ± 5.4 g, Z = -2.95, p = 0.003). δ13C value was able to predict AS intake using a blood sample within this population subset. The single-isotope prediction equation may be an alternative method to assess AS intake and is more objective, cost-feasible, and efficient than traditional dietary assessment methods. However, more research is needed to assess this biomarker with rigorous study designs such as controlled feeding.


Multiple stafne bone defects: a rare entity.
Stafne bone defects (SBDs) are generally located in the lingual cortex, close to the mandibular angle. We report the occurrence of multiple SBDs in an asymptomatic patient, a 60-year-old man, referred to a radiology clinic to undergo examination for the purpose of implant planning. The case of multiple SBD presented here, probably the first reported in the literature, reinforces the hypothesis that some cases of SBD may be the result of a focal failure during the ossification of the mandible.