Aromatic DNA adducts and breast cancer risk: a case-cohort study within the EPIC-Spain.
Epidemiologic evidence linking environmental exposure to polycyclic aromatic hydrocarbons (PAH) with breast cancer is limited. Measurement of DNA adducts formed by aromatic compounds, including PAH, has been carried in breast tissue samples and white blood cells from women with breast cancer and different kinds of controls. However, these studies provide inconsistent results and bias cannot be ruled out. During the 7-year follow-up period, 305 women were diagnosed with first primary breast cancer in the EPIC-Spain cohort, and were compared with a sample of 149 women without breast cancer at recruitment, using a case-cohort approach. Aromatic adducts to DNA from leukocytes collected at recruitment were measured by means of the 32P-post-labelling technique. The relative risk and 95% confidence interval (CI), adjusted by relevant confounders, were estimated by a modified version of Cox proportional hazards model. There was a significant increased risk for developing breast cancer when DNA adduct concentrations were doubled, with adjusted RR of 1.61 (95% CI 1.29-2.01). The increase in breast cancer risk was observed both for pre- and post-menopausal women. There was a significant interaction with tobacco smoking and body mass index, with higher effect of DNA adducts on breast cancer risk among smokers and women with normal weight. The results from our study support the hypothesis that factors leading to higher levels of aromatic DNA adducts in white blood cells may be involved in development of breast cancer.


Delays in Initiating Anti-Cancer Therapy for Early-Stage Breast Cancer-How Slow Can We Go?
Breast cancer is the most commonly diagnosed cancer among women worldwide, and is a leading cause of cancer-related deaths. When diagnosed at an early stage, appropriate and timely treatment results in a high cure rate and better quality of life. Delays in initiating anti-cancer therapy, including surgical resection, adjuvant/neoadjuvant chemotherapy and radiation therapy are commonly encountered, even in developed health care systems. Existing comorbidities that mandate referral to other services, genetic counseling and testing that may dictate the extent and type of anti-cancer therapy and insurance coverage, are among the most commonly cited factors. However, delays can be unavoidable; for over three years, health care systems across the globe were busy dealing with the unprecedented COVID-19 pandemic. War across hot zones around the globe resulted in millions of refugees; most of them have no access to cancer care, and when/where available, there may be significant delays. Thus, cancer patients across the globe will probably continue to suffer from significant delays in diagnosis and appropriate treatment. Many retrospective reports showed significant negative impacts on different aspects of treatment outcomes and on patients' psychosocial wellbeing and productivity. In this paper, we review the available data on the impact of delays in initiating appropriate treatment on the outcomes of patients with early-stage breast cancer.


Gene fitness landscapes of Vibrio cholerae at important stages of its life cycle.
Vibrio cholerae has evolved to adeptly transition between the human small intestine and aquatic environments, leading to water-borne spread and transmission of the lethal diarrheal disease cholera. Using a host model that mimics the pathology of human cholera, we applied high density transposon mutagenesis combined with massively parallel sequencing (Tn-seq) to determine the fitness contribution of >90% of all non-essential genes of V. cholerae both during host infection and dissemination. Targeted mutagenesis and validation of 35 genes confirmed our results for the selective conditions with a total false positive rate of 4%. We identified 165 genes never before implicated for roles in dissemination that reside within pathways controlling many metabolic, catabolic and protective processes, from which a central role for glycogen metabolism was revealed. We additionally identified 76 new pathogenicity factors and 414 putatively essential genes for V. cholerae growth. Our results provide a comprehensive framework for understanding the biology of V. cholerae as it colonizes the small intestine, elicits profuse secretory diarrhea, and disseminates into the aquatic environment.


Secondary Exposure of Family Members to Cyclophosphamide After Chemotherapy of Outpatients With Cancer: A Pilot Study.
To measure the total amount of cyclophosphamide (CPA) excreted in the urine of patients with cancer and their cohabitating family members seven days after CPA administration. Biological monitoring. . Home setting with outpatients receiving chemo-therapy. 8 patients administered CPA, 10 cohabitating family members, and 10 control participants. During the first seven days after CPA administration, urine samples were collected from the participants. The samples were analyzed for the unchanged form of CPA using gas chromatography in tandem with mass spectroscopy. CPA levels . CPA was detected in 112 of 276 patient urine samples. The last sample containing detectable CPA levels was collected after more than 48 hours in 63% of the patients, with a maximum length of five days post-treatment. In addition, 243 urine samples were collected from family members, and CPA was detected in the samples of five family members (17-252 ng per member). CPA was not detected in any control participants. These findings indicate that family members in close contact with patients receiving CPA are at high risk for drug exposure as many as seven days post-treatment . Nurses should educate patients and their family members about preventing exposure to antineoplastic drugs in the home setting.


An axoplasmic component of the Schmidt-Lanterman deformation.
In three instances, peripheral nerves containing numerous Schmidt-Lanterman discontinuities of myelin revealed transverse, wedge-shaped, or arrowhead-shaped axoplasmic excrescences visible with axon stains. These were arranged with a frequency and length like that of the myelin clefts, but the axonal materials were located within the myelin masses bordering the clefts, not in the clefts themselves. These axoplasmic changes are not consistent with most assumptions concerning the physiologic functions of the clefts, and supports the concept that the clefts are artifactual, due possibly to mechanical factors acting an abnormal nerve fibers.


Intensive care in developing countries in the Western Pacific.
The rapid economic, scientific, and technologic development in Asia probably is the most important in the world today. Eventually, the development of health care and critical care medicine in the Western Pacific will be affected. Even with the problems that have to be faced, the future of critical care medicine in the region looks promising.However, the leaders of critical care medicine in each country should identify the model of intensive care practice that is the most appropriate for their country. Each country needs to assign an appropriate rank of priority to intensive care. There is a great need for simple, inexpensive therapeutic interventions and methods for monitoring critically ill patients that can be shown to be effective. Efficient systems for transporting critically patients are also needed. Simple ventilators with inexpensive monitors and defibrillators are the technology that is most needed. Good referral systems and greater use of physician extenders, such as nurse practitioners, to provide enhanced access to specialist care for critical illness should be promoted. A few high-standard ICUs with good facilities for education and training should be organized on a regional basis in each country.


[A case of Goodpasture's syndrome with myeloperoxidase specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) during chronic interstitial pneumonia].
A 55-year-old man was admitted to our hospital with of hemoptysis, progression of anemia and renal failure in February, 1996. Idiopathic interstitial pneumonia had been diagnosed and he had been followed at a regional hospital since 1988. On the third day after admission, he suffered from sudden and massive hemoptysis. Goodpasture's syndrome was diagnosed because anti-GBM antibody was detected in serum. A high titer of MPO-ANCA was also recognized simultaneously. Steroid pulse therapy, immunosuppressive therapy, and plasmapheresis were begun, but he died on the 28th hospital day because of severe hypoxemia and multi-organ failure. Histological examination after autopsy revealed crescentic glomerulonephritis with linear deposition of IgG in the glomerular capillary wall, and interstitial pneumonia accompanied by massive alveolar hemorrhage. It was suggested that in this patient, not only anti-GBM antibody but also circulating MPO-ANCA might have participated in the progression of the crescentic glomerulonephritis and alveolar hemorrhage observed in Goodpasture's syndrome.


A new class of focusing crystal shapes for Bragg spectroscopy of small, point-like, x-ray sources in laser produced plasmas.
This paper describes a new class of focusing crystal forms for the x-ray Bragg crystal spectroscopy of small, point-like, x-ray sources. These new crystal forms are designed with the aid of sinusoidal spirals, a family of curves, whose shapes are defined by only one parameter, which can assume any real value. The potential of the sinusoidal spirals for the design x-ray crystal spectrometers is demonstrated with the design of a toroidally bent crystal of varying major and minor radii for measurements of the extended x-ray absorption fine structure near the Ta-L3 absorption edge at the National Ignition Facility.


RF gradient BIRD/TANGO sequence to eliminate uncoupled magnetization.
A modification of the BIRD and TANGO sequences is presented which employs radiofrequency field gradients to eliminate the net magnetization from uncoupled spins, while completely preserving coupled magnetization. The standard BIRD and TANGO sequences cause selective nutation of protons directly bound to a coupling partner, while returning uncoupled magnetization to +z. These sequences lend themselves naturally to modification using RF gradients, which require no increase in pulse-sequence complexity while providing substantial suppression of uncoupled resonances and elimination of typical antiphase and multiple-quantum error terms that arise from improperly set pulse lengths or delays. In the RF-gradient BIRD/TANGO sequence, the uncoupled magnetization is dephased in a plane orthogonal to the RF axis, while the desired signal components are refocused, effectively in a rotary echo. The sequence has applications to solvent suppression and selective isotopomer excitation. It is demonstrated for selective excitation of the satellites in a sample of chloroform, yielding suppression of the uncoupled magnetization by factor of approximately 800.


Lymph node assessment in cervical cancer: prognostic and therapeutic implications.
Lymph node status is not part of the staging system for cervical cancer, but provides important information for prognosis and treatment. This article reviews the incidence and patterns of lymph node metastasis, and the issues surrounding surgical assessment of lymph nodes. The preoperative assessment of lymph nodes by imaging, as well as the intraoperative assessment by sentinel nodes will be discussed. Finally, the prognostic and therapeutic implications of lymphadenectomy in cervical cancer will be reviewed.


Moving the four habits model into dentistry. Development of a dental consultation model: Do dentists need an additional habit?
A consultation model for dentistry is presented, with communication skills in a didactic and structural format, applicable for most types of visits, patients and problems. A characteristic of the dental visit is its division into dialogue phases and clinical phases, which makes verbal exchange especially challenging. The original Four Habits Model (4H) has been adapted from medicine to the specific structure and content of a dental visit, and a modified model is proposed. The dental model consists of a structural core framework relevant for all dental consultations, and additional extensions applicable to commonly occurring issues. Facilitate Perceived Control has been added to the model, due to its crucial importance in dental visits, and we suggest naming the model "The Four + One Habits Model for Dental Visits (4 + 1HD)." The proposed model should have clinical relevance for improving patient care and patient experience, as well as easing the busy everyday life for dentists in a variety of clinical settings. It is also likely to be a flexible framework for communication skills training at all levels of dental education. More research is needed to validate and test the model in various clinical and educational settings.


Mouse Bone Marrow Sca-1+ CD44+ Mesenchymal Stem Cells Kill Avirulent Mycobacteria but Not Mycobacterium tuberculosis through Modulation of Cathelicidin Expression via the p38 Mitogen-Activated Protein Kinase-Dependent Pathway.
Mycobacterium tuberculosis primarily infects lung macrophages. However, a recent study showed that M. tuberculosis also infects and persists in a dormant form inside bone marrow mesenchymal stem cells (BM-MSCs) even after successful antibiotic therapy. However, the mechanism(s) by which M. tuberculosis survives in BM-MSCs is still not known. Like macrophages, BM-MSCs do not contain a well-defined endocytic pathway, which is known to play a central role in the clearance of internalized mycobacteria. Here, we studied the fate of virulent and avirulent mycobacteria in Sca-1+ CD44+ BM-MSCs. We found that BM-MSCs were able to kill avirulent Mycobacterium smegmatis and Mycobacterium bovis BCG but not the pathogenic species M. tuberculosis Further mechanistic studies revealed that pathogenic M. tuberculosis dampens the antibacterial response of BM-MSCs by downregulating the expression of the cationic antimicrobial peptide cathelicidin. In contrast, avirulent mycobacteria were effectively killed by inducing the Toll-like receptor 2/4 (TLR2/4) pathway-dependent expression of cathelicidin, while small interfering RNA (siRNA)-mediated cathelicidin silencing increased the survival of M. bovis BCG in BM-MSCs. We also showed that M. bovis BCG infection caused increased expression levels of MyD88, phospho-interleukin-1 receptor-associated kinase 4 (pIRAK-4), and the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Further downstream investigations demonstrated that IRAK-4-p38 activation increased the nuclear translocation of NF-κB, which subsequently induced the expression of cathelicidin and the cytokine interleukin-1β (IL-1β), resulting in the decreased survival of M. bovis BCG. On the other hand, inhibition of TLR2/4, pIRAK-4, p38, and NF-κB nuclear translocation decreased cathelicidin and IL-1β expression levels and therefore increased the survival of avirulent mycobacteria. This is the first report that demonstrates that virulent mycobacteria manipulate the TLR2/4-MyD88-IRAK-4-p38-NF-κB-Camp-IL-1β pathway to survive inside bone marrow stem cells.


Chronic and acute inspiratory muscle loading augment the effect of a 6-week interval program on tolerance of high-intensity intermittent bouts of running.
This study examined the hypothesis that chronic (training) and acute (warm-up) loaded ventilatory activities applied to the inspiratory muscles (IM) in an integrated manner would augment the training volume of an interval running program. This in turn would result in additional improvement in the maximum performance of the Yo-Yo intermittent recovery test in comparison with interval training alone. Eighteen male nonprofessional athletes were allocated to either an inspiratory muscle loading (IML) group or control group. Both groups participated in a 6-week interval running program consisting of 3-4 workouts (1-3 sets of various repetitions of selected distance [100-2,400 m] per workout) per week. For the IML group, 4-week IM training (30 inspiratory efforts at 50% maximal static inspiratory pressure [P0] per set, 2 sets·d-1, 6 d·wk-1) was applied before the interval program. Specific IM warm-up (2 sets of 30 inspiratory efforts at 40% P0) was performed before each workout of the program. For the control group, neither IML was applied. In comparison with the control group, the interval training volume as indicated by the repeatability of running bouts at high intensity was approximately 27% greater in the IML group. Greater increase in the maximum performance of the Yo-Yo test (control: 16.9 ± 5.5%; IML: 30.7 ± 4.7% baseline value) was also observed after training. The enhanced exercise performance was partly attributable to the greater reductions in the sensation of breathlessness and whole-body metabolic stress during the Yo-Yo test. These findings show that the combination of chronic and acute IML into a high-intensity interval running program is a beneficial training strategy for enhancing the tolerance to high-intensity intermittent bouts of running.


[Prevalence of decubitus lesions in a hospital in Lombardia].
A one day prevalence survey was performed in a University Hospital, with the aim of assessing the risk of developing a pressure sore by patients systematically assessed with the Waterlow Scale. Out of the 141 at risk patients, 16 had a pressure sore (11.3%). For six of them the sore was already present at admission so that the in hospital incidence was 7% (10 patients). Most at risk patients (74.4) were still cared on a standard mattress. The advantages and limits of prevalence surveys are discussed at the end of the three articles that present a prevalence survey, an incidence survey and the study of sentinel events.


An Exploration of the Effectiveness of Different Intensity Protocols of Modified Constraint-Induced Therapy in Stroke: A Systematic Review.
To examine the effectiveness of different modified Constraint-Inuced Therapy (mCIMT) protocol intensities on upper extremity motor function in adults with hemiplegia. A search was conducted in PubMed, Scopus, EBSCO, and Cochrane Library for articles published between April 2010 and December 2021. Only randomized controlled trials (RCTs) were included. Studies were excluded if they used a sample of less than five, mCIMT in combination with other therapy, and/or if they were not written in English. Methodologic quality was assessed using the Cochrane collaboration risk of bias tool-2. Thirty-six RCTs with a total of 721 participants were included. Most researchers followed a moderate to low protocol intensity in terms of total treatment time and moderate to high intensity with regard to restriction time. Almost all of the upper limb motor function measures showed statistically significant improvements (p < .05) after mCIMT, irrespective of the protocol's intensity, but there was lack of high-quality studies. Statistically significant improvements did not always translate to clinical importance. Low-intensity CIMT protocols may result in comparable improvements to more intensive ones but caution has to be taken when drawing conclusions due to high risk of bias studies.


[pH-Testing - experience in clinical practice in a pulmonary division].
The association between lung disease and gastroesophageal reflux has been discussed for a long time. Aim of this retrospective study was to clarify evidence and acceptance of pH-testing in a pulmonary division. pH-testing data at the Krankenhaus Grosshansdorf from January 2000 till March 2004 was evaluated and clinical and pulmonary functional data assessed. A total of 186 patients (113 female, 73 male) received a pH-monitoring. The most important indication was chronic cough (94.6 %). Of 165 evaluable subjects, 63 patients had asthma, 54 patients chronic cough, 18 COPD and 30 patients various diseases (fibrosis, pneumonia, tuberculosis, bronchiectasis a. s. o.). 51 % of patients showed a pathological gastroesophageal reflux (median DeMeester score 22.3). Neither BMI nor patient subgroups correlated significantly with DeMeester score. In 62 % of asthmatics, 57 % of patients with chronic cough and 33 % of COPD patients a pathological reflux was found. In the subgroup with various diseases there was pathological reflux detected in 30 %. pH-testing is a reliable and safe method to determine gastroesophageal reflux in pulmonary diseases. Pathological reflux is frequently found even without typical symptoms. It remains unclear whether there is a causal relationship.


Nonsmall cell lung carcinoma with neuroendocrine differentiation--an entity of no clinical or prognostic significance.
The existence of non-small cell lung carcinoma with neuroendocrine differentiation as a distinct entity and its relevance for prognostic and treatment purposes is controversial. This study assesses the frequency and biologic and prognostic significance of neuroendocrine (NE) expression of synaptophysin (SNP), chromogranin (Ch), and neural cell adhesion molecule (N-CAM) using tissue microarray (TMA) and immunohistochemistry. Six hundred nine nonsmall cell lung carcinomas (NSCLCs) were reviewed for subclassification. TMA blocks were made using duplicate 0.6-mm-diameter tissue cores and slides stained with SNP, Ch, and N-CAM. Immunoreactivity was considered if 1% or more of tumor cells were positive. Hematoxylin and eosin-stained sections were subclassified as: 243 adenocarcinoma (ACA), 272 squamous cell carcinoma (SCC), 35 large cell carcinoma, 32 non-small cell carcinoma NOS, and 6 other (carcinosarcoma, giant cell carcinoma). Positivity for either marker was identified in 13.6% of NSCLC (76/558). NSCLC showed reactivity for Ch in 0.4% of cases (2/524), for SNP in 7.5% of cases (39/521) and for N-CAM in 8.6% of cases (44/511), whereas only 0.2% of cases (1/517) showed coexpression of SNP and Ch and none of all 3 markers. The assessment of NE differentiation in NSCLC is unnecessary and expensive and is of no clinical or prognostic significance. SNP or N-CAM stains a small minority of NSCLC, whereas Ch immunoreactivity is less common. Positivity for any 2 NE markers is rare. SNP is more likely to be expressed in adenocarcinoma (P=0.01) and N-CAM in squamous-cell carcinoma (P=0.008). Otherwise there was no correlation between immunoreactivity and tumor morphology. Disease specific and overall survival is not influenced by NE differentiation and therefore non-small cell lung carcinoma with neuroendocrine differentiation should not be a subclass distinct from the other NSCLC.


The midbrain periaqueductal gray in the rat, cat, and monkey: a Nissl, Weil, and Golgi analysis.
Anatomical staining methods including Nissl, Weil, Golgi, and horseradish peroxidase stain have been used to elucidate the cyto- and myeloarchitectural organization of the periaqueductal gray in monkey, cat, and rat. From these various staining methods it appears that the periaqueductal gray is composed of a tightly packed group of cells, which show a slight increase in soma size, dendritic diameter, and degree of myelinization from central to peripheral borders. This central gray region contains a wide variety of cell types including multipolar, fusiform, stellate, and pyramidal neurons. Clearly delineated subnuclei, distinguished on the basis of soma size, dendritic arborizations, pigmentation, or evidence of cytological individuality could not be discerned in this study. Together with the immunohistochemical and connectivity studies the present data suggest that the neuronal organization of the PAG could be described as a mosaic of clusters of functional related neurons rather than as three distinct subnuclei, each with its own unique cytoarchitecture and connectivity.


Pathophysiological roles of transglutaminase - catalyzed reactions in the pathogenesis of human diseases.
Transglutaminases (TGs, E.C. 220.127.116.11) are related and ubiquitous enzymes which catalyze the cross linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate. These enzymes are also capable of catalyzing other reactions which are important for cell life. To date, at least eight different human TGs have been identified. The distribution and the physiological roles of human TGs have been widely studied in numerous cell types and tissues and recently their roles in several diseases have begun to be identified. It has been hypothesized that transglutaminase activity is directly involved in the patho-genetic mechanisms responsible for several human diseases. In particular, TG2, a member of the TG enzyme family, has been shown to be involved in the molecular mechanisms responsible for a very widespread human pathology, Celiac Disease (CD), one of the most common food intolerances described in the western population. The main food agent that provokes the strong and diffuse clinical symptoms has been known for several years to be gliadin, a protein present in a very large number of human foods derived from vegetables. The aim of this review is to summarize the most recent findings concerning the relationships between the biochemical properties of the transglutaminase activity and the basic molecular mechanisms responsible for CD. In addition, we present some clinical associations of CD with other human diseases, with particular reference to neuropsychiatric disorders. Possible molecular links between biochemical activities of transglutaminase enzymes, CD and neuropsychiatric disorders are discussed.


Iodine(V)-Based Oxidants in Oxidation Reactions.
The chemistry of hypervalent iodine reagents has now become quite valuable due to the reactivity of these compounds under mild reaction conditions and their resemblance in chemical properties to transition metals. The environmentally friendly nature of these reagents makes them suitable for Green Chemistry. Reagents with a dual nature, such as iodine(III) reagents, are capable electrophiles, while iodine(V) reagents are known for their strong oxidant behavior. Various iodine(V) reagents including IBX and DMP have been used as oxidants in organic synthesis either in stoichiometric or in catalytic amounts. In this review article, we describe various oxidation reactions induced by iodine(V) reagents reported in the past decade.


Platelet-derived growth factor (PDGF) cross-signaling via non-corresponding receptors indicates bypassed signaling in colorectal cancer.
Platelet-derived growth factor (PDGF) signaling, besides other growth factor-mediated signaling pathways like vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), seems to play a crucial role in tumor development and progression. We have recently provided evidence for upregulation of PDGF expression in UICC stage I-IV primary colorectal cancer (CRC) and demonstrated PDGF-mediated induction of PI3K/Akt/mTOR signaling in CRC cell lines. The present study sought to follow up on our previous findings and explore the alternative receptor cross-binding potential of PDGF in CRC. Our analysis of primary human colon tumor samples demonstrated upregulation of the PDGFRβ, VEGFR1, and VEGFR2 genes in UICC stage I-III tumors. Immunohistological analysis revealed co-expression of PDGF and its putative cross-binding partners, VEGFR2 and EGFR. We then analyzed several CRC cell lines for PDGFRα, PDGFRβ, VEGFR1, and VEGFR2 protein expression and found these receptors to be variably expressed amongst the investigated cell lines. Interestingly, whereas Caco-2 and SW480 cells showed expression of all analyzed receptors, HT29 cells expressed only VEGFR1 and VEGFR2. However, stimulation of HT29 cells with PDGF resulted in upregulation of VEGFR1 and VEGFR2 expression despite the absence of PDGFR expression and mimicked the effect of VEGF stimulation. Moreover, PDGF recovered HT29 cell proliferation under simultaneous treatment with a VEGFR or EGFR inhibitor. Our results provide some of the first evidence for PDGF cross-signaling through alternative receptors in colorectal cancer and support anti-PDGF therapy as a combination strategy alongside VEGF and EGF targeting even in tumors lacking PDGFR expression.


High-frequency repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex of patients with Parkinson's disease and treatment-resistant depression: a pilot study.
An increasing amount of evidence is showing the therapeutic effects of rTMS on PD-related non-motor functions neuroanatomically linked to the DLPFC. This presents an ongoing need to apply an optimal combination of stimulation parameters to clinically heterogeneous patient populations, including those with neuropsychiatric problems and other comorbidities along with the neurodegenerative process. In this prospective pilot study, six patients with PD and treatment-resistant depression were thoroughly assessed and carefully monitored before, during, and after each stimulation procedure. The results can provide the basis for developing an extended rTMS protocol that is both effective and safe.


Significance of low body weight in ovulatory dysfunction after stopping oral contraceptives.
In a group of patients who developed ovulatory dysfunction on stopping oral contraception the mean body weight of those with previosly regular cycles was significantly lower than that of women who had had ovulatory dysfunction beforeoral contraception and also that of a control group. Women of low body weight may be at particular risk of developing post-pill amenorrhoea even when there is no history pointing to ovulatory dysfunction. This should be considered when selecting a form of contraception in such women.


Current concepts in the role of steroids in the treatment of sprains and strains.
With the development of nonsteroidal anti-inflammatory drugs, the use of corticosteroids in the treatment of sprains and strains has greatly diminished. They are used occasionally in the treatment of tendinitis in various areas of the body, but they are not used for ligamentous sprains and muscle strains. Injection of corticosteroids into ligaments, tendons and joints is often quite controversial and most clinicians have abandoned their use in the treatment of common athletic injuries.


Sunlight and cortical cataract.
We undertook a prospective clinical study to test our initial impression that cortical opacities are seldom present in the upper part of the lens. Data analysis revealed that of 174 eyes having cortical opacities, only 15 (8.62%) had opacities in the area of the lens between the 10- and 2-o'clock positions. Lid retraction, defined as upper lid position at or above the limbus, was seen in 13 (88.66%) of these eyes. Our study indicates that in the absence of lid retraction, cortical opacities are very rarely seen in the upper segment of the lens, a segment that is normally covered by the upper lid. This suggests a protective effect of the upper lid against cortical opacities, and indirectly it supports the theory that senile cortical opacities may be the result of thermal damage to the lens.


[Surgical treatment of metastatic lesions of the long tubular bones].
The results of surgical treatment of 12 patients with metastases in long tubular bones are presented. Palliative surgery-reaction of the heads of bones or removal of the entire long tubular bone with prosthetic replacement--was performed in all cases. All the patients went through the operation well and were discharged from hospital. Pain subsided in all cases and the patients make satisfactory use of the operated extremities. The average survival time by the data of this report was 10.6 months. No local recurrences after bone resections were registered. Due to palliative surgery for metastases into long tubular bones, the patients do not suffer from pain, are mobile and self dependent again. A long survival time may be expected in some cases (solitary metastases), when such palliative procedures are employed.


Clinical and radiological evaluation of implants placed with osteotome sinus lift technique: 19-month follow-up.
Implant placement in the posterior region of the maxilla might be problematic due to poor regional bone quality. The aim of this study was to clinically and radiologically evaluate implants which were placed in the posterior region of the maxilla (with insufficient bone height) with osteotome sinus lift technique after 19-month follow-up. Twenty-four patients with posterior maxillary alveolar height ranging from 5 to 8 mm were chosen for this prospective study. After breaking of the cortical bony sinus floor, sufficient bone substitute was placed, and sinus floor was elevated. In this way, a new sinus floor was created, which was designated for further implants placement. Fifty implants were placed immediately after osteotomy sinus lift technique. The mean clinical and radiological follow-up period was 19 months (with a range of 14-24 months). Success factors such as the absence of mobility, pain, infection, and the amount of crestal bone loss were determined in this study. For data analyzing, Kruskal-Wallis and Mann-Whitney tests were used. After 19 months, results showed 96% success rate. Two out of fifty implants failed due to mobility. The mean depth of implants in sinus, mean height of residual crestal bone before surgery, and the mean rate of crestal bone loss were 3.8, 7.9, and 0.71 mm, respectively. Osteotome sinus lift technique is a noninvasive surgical method for enhancing a desired length. Furthermore, implants insertion was successful after osteotome sinus lift technique in cases with insufficient bone height.


Mechanisms of renal blood flow autoregulation: dynamics and contributions.
Autoregulation of renal blood flow (RBF) is caused by the myogenic response (MR), tubuloglomerular feedback (TGF), and a third regulatory mechanism that is independent of TGF but slower than MR. The underlying cause of the third regulatory mechanism remains unclear; possibilities include ATP, ANG II, or a slow component of MR. Other mechanisms, which, however, exert their action through modulation of MR and TGF are pressure-dependent change of proximal tubular reabsorption, resetting of RBF and TGF, as well as modulating influences of ANG II and nitric oxide (NO). MR requires < 10 s for completion in the kidney and normally follows first-order kinetics without rate-sensitive components. TGF takes 30-60 s and shows spontaneous oscillations at 0.025-0.033 Hz. The third regulatory component requires 30-60 s; changes in proximal tubular reabsorption develop over 5 min and more slowly for up to 30 min, while RBF and TGF resetting stretch out over 20-60 min. Due to these kinetic differences, the relative contribution of the autoregulatory mechanisms determines the amount and spectrum of pressure fluctuations reaching glomerular and postglomerular capillaries and thereby potentially impinge on filtration, reabsorption, medullary perfusion, and hypertensive renal damage. Under resting conditions, MR contributes approximately 50% to overall RBF autoregulation, TGF 35-50%, and the third mechanism < 15%. NO attenuates the strength, speed, and contribution of MR, whereas ANG II does not modify the balance of the autoregulatory mechanisms.


Secretion of heterologous thermostable cellulases in Bacillus subtilis.
Bacillus subtilis is used industrially for the production of secreted enzymes. The most characteristic feature of the secreted enzymes is variation in the N-terminal signal peptides that is recognized by secretion machinery, which is one of the determinants of efficiency and must be customized in each case. Culturing cellulolytic B. subtilis to secrete heterologous cellulases combined with customized signal peptides would be beneficial for producing biocommodities from cellulosic biomass. Four Clostridium thermocellum genes, encoding endoglucanases (celA and celB) and exoglucanases (celK and celS) were cloned to construct random libraries of combinations with 173 different signal peptides originating from the B. subtilis genome. The libraries were successfully screened to identify the signal peptides most efficient in secretion of each of the four cellulases, which were theoretically unpredictable. The secreted cellulases were assayed on carboxymethyl cellulose, phosphoric acid swollen cellulose, and microcrystalline cellulose to determine the possible effects of the signal peptides on substrate specificity. The customized signal peptides for CelA, CelB, and CelS did not affect enzyme performance but those for CelK might influence its substrate specificity.


Smart Copolymer Surface Derived from Geminized Cationic Amphiphilic Polymers for Reversibly Switchable Bactericidal and Self-Cleaning Abilities.
Bacterial adhesion and colonization on material surfaces pose a serious problem for healthcare-associated devices. Cationic amphiphilic polymer brushes are usually used as surface coatings in antibacterial materials to endow an interface with excellent bactericidal efficiency, but they are easily contaminated, which puts a great limitation on their application. Herein, novel antibacterial copolymer brush surfaces containing geminized cationic amphiphilic polymers (pAGC8) and thermoresponsive poly(N-isopropylacrylamide) polymers (pNIPAm) have been synthesized. Surface functionalization of polymer brushes was investigated by X-ray photoelectron spectroscopy, spectroscopic ellipsometry, atomic force microscopy, and water contact angle measurements. A proportion of AGC8 and NIPAm units in copolymer brushes has been adjusted to obtain a high-efficiency bactericidal surface with minimal interference to its self-cleaning property. The killing and releasing efficiency of the optimized surface simultaneously reached up to above 80% for both Staphylococcus aureus and Escherichia coli bacteria, and the bactericidal and self-cleaning abilities are still excellent even after three kill-release cycles. Such a novel copolymer brush system provides innovative guidance for the development of high-efficiency antibacterial materials in biomedical application.


How the Ribosomal A-Site Finger Can Lead to tRNA Species-Dependent Dynamics.
Proteins are synthesized by the joint action of the ribosome and tRNA molecules, where the rate of synthesis can be affected by numerous factors, such as the concentration of tRNA, the binding affinity of tRNA for the ribosome, or post-transcriptional modifications. Here, we expand this range of contributors by demonstrating how differences in tRNA structure can give rise to tRNA species-specific dynamics in the ribosome. To show this, we perform simulations of A/P hybrid-state formation for two tRNA species (tRNAPhe and tRNALeu), which differ in the size of their variable loops (VLs). These calculations reveal that steric interactions between the VL and the ribosomal A-site finger (ASF, i.e., H38 of 23S rRNA) can directly modulate the free-energy landscape for each tRNA species. We also find that tRNA and ASF motions are highly correlated, where fluctuations of the ASF are predictive of tRNA transition events. Finally, by introducing perturbations to the model, we demonstrate that ASF flexibility is a determinant of the rate of A/P hybrid-state formation.


Study of Bayesian variable selection method on mixed linear regression models.
Variable selection has always been an important issue in statistics. When a linear regression model is used to fit data, selecting appropriate explanatory variables that strongly impact the response variables has a significant effect on the model prediction accuracy and interpretation effect. redThis study introduces the Bayesian adaptive group Lasso method to solve the variable selection problem under a mixed linear regression model with a hidden state and explanatory variables with a grouping structure. First, the definition of the implicit state mixed linear regression model is presented. Thereafter, the Bayesian adaptive group Lasso method is used to determine the penalty function and parameters, after which each parameter's specific form of the fully conditional posterior distribution is calculated. Moreover, the Gibbs algorithm design is outlined. Simulation experiments are conducted to compare the variable selection and parameter estimation effects in different states. Finally, a dataset of Alzheimer's Disease is used for application analysis. The results demonstrate that the proposed method can identify the observation from different hidden states, but the results of the variable selection in different states are obviously different.


[Discussion on the transcription and circulation of "Shouzhuo Sanctum" version of Qing nang mi jue (Secret Instructions of Sore and Abscess) based on the stone tablet inscriptions and contracts].
He Gaomin, the discoverer of the book Qing nang mi jue (Secret Instructions of Sore and Abscess) considered that this book was written by Fu Shan of the late Ming and early Qing Dynasties, which was first stored secretly by Zhang Shixue, and then transcribed by "Pan zi" , and further copied by Wang Dade in the First Year of Yongzheng Reign. According to the folk literature including inscriptions on stone tablet and contracts, combining with the dictations of Zhang's descendants, suggesting that Zhang's Family was a medical family for generations and Zhang Shixue was a doctor in Miaodao Town, Jiyuan County, Huaiqing Prefecture of Henan during the reigns of the Qianlong and Jiaqing Emperor of the Qing Dynasty. He might not be earlier than the secret collection of the book by Wang Dade, and nobody knows where Zhang got the book. Zhang's family fortunes declined in the late Qing Dynasty, and the version of Qing nang mi jue preserved secretly by Zhang Shixue spread to the market and obtained by Li Yinyuan, whose son Li Qu brought it into Shanxi, and was thus found by He Gaomin.


Untargeted metabolomic analysis of aqueous humor in diabetic macular edema.
The mechanism of diabetic macular edema (DME) was explored by comparing the intraocular metabolite profiles of the aqueous humor of patients with DME to those of diabetic patients without DME using untargeted metabolomic analysis. Aqueous samples from 18 type 2 diabetic patients with DME and 18 type 2 diabetic patients without DME used as controls were analyzed using liquid chromatography-mass spectrometry (LCMS). The two groups of patients were age and gender matched and had no systemic diseases other than diabetes mellitus (DM). The metabolites were analyzed using orthogonal partial least square discriminant analysis. The metabolite profiles in DME patients differed from those in DM controls. This indicates the following metabolic derangements in DME: (a) a higher amount of oxidized fatty acids but a lower amount of endogenous antioxidants (oxidative stress); (b) higher levels of β-glucose and homocysteine but a lower level of sorbitol (hyperglycemia); (c) a higher amount of prostaglandin metabolites (inflammation); (d) higher amounts of acylcarnitines, odd-numbered fatty acids, and 7,8-diaminononanoate (respiration deterioration); (e) a higher amount of neurotransmitter metabolites and homovanillic acid (neuronal damage); (f) a lower amount of extracellular matrix (ECM) constituents (ECM deterioration); and (g) a higher amount of di-amino peptides (microvascular damage). The change in the metabolic profiles in the aqueous humor of DME patients compared to DM controls without DME indicates that DME patients may have less capability to resist various stresses or damaging pathological conditions, such as oxidative stress, mitochondrial insufficiency, inflammation, and ECM deterioration.


Consensus topography in the ATP binding site of the simian virus 40 and polyomavirus large tumor antigens.
The location and sequence composition of a consensus element of the nucleotide binding site in both simian virus 40 (SV40) and polyomavirus (PyV) large tumor antigens (T antigens) can be predicted with the assistance of a computer-based pattern-matching system, ARIADNE. The latter was used to optimally align elements of T antigen primary sequence and predicted secondary structure with a "descriptor" for a mononucleotide binding fold. Additional consensus elements of the nucleotide binding site in these two proteins were derived from comparisons of T antigen primary and predicted secondary structures with x-ray structures of the nucleotide binding sites in four otherwise unrelated proteins. Each of these elements was predicted to be encompassed within a 110-residue segment that is highly conserved between the two T antigens residues 418-528 in SV40 T antigen and residues 565-675 in PyV). Results of biochemical and immunologic experiments on the nucleotide binding behavior of these proteins were found to be consistent with these predictions. Taken together, the latter have resulted in a topological model of the ATP binding site in these two oncogene products.


An examination of soil and water conservation practices in the paddy fields of Guilan province, Iran.
This study examined the use of soil and water conservation (SWC) practices among rice farmers in Iran. A random sample of 400 rice paddy farmers in the Foumanat plain of Guilan province, who use SWC measures, was drawn from a population of 52 thousand farmers. A two-part questionnaire was used to examine the level of utilization of SWC practices and to profile paddy farmers. Internal consistency was demonstrated with a coefficient alpha of 0.76, and the content and face validity of the instrument was confirmed by a panel of soil and water experts. Descriptive and analytical statistics were used to analyze the data. Results of ANOVA indicated that the mean levels of SWC practices vary considerably at the 0.01 level of significance by groups of age, education, non-agricultural income, production costs, yield, cultivated paddies and distance from home to the farm or to the main road. Similarly, significant differences were observed by groups of family size, rice production, ownership of livestock and profits from rice production at 0.05 level. The levels of experience in agriculture and ownership of poultry were found to have no significant effects on SWC practices.


Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes.
1,1-Difluoro-1-alkenes bearing a biaryl-2-yl group effectively underwent site-selective intramolecular iodoarylation by the appropriate cationic iodine species. Iodoarylation of 2-(2-aryl-3,3-difluoroallyl)biaryls proceeded via regioselective carbon-carbon bond formation at the carbon atoms in β-position to the fluorine substituents, thereby constructing dibenzo-fused six-membered carbocycles bearing a difluoroiodomethyl group. In contrast, 2-(3,3-difluoroallyl)biaryls underwent a similar cyclization at the α-carbon atoms to afford ring-difluorinated seven-membered carbocycles.


Synthesis of indolizidines and pyrrolizidines through the [2 + 2]cycloaddition of five-membered endocyclic enecarbamates to alkyl ketenes. Unusual regioselectivity of Baeyer-Villiger ring expansions of alkyl aza-bicyclic cyclobutanones.
The total syntheses of two indolizidine skeletons and of the necine base (+/-)-platynecine were accomplished in a concise manner with good overall yields starting from a common five-membered endocyclic enecarbamate. These syntheses feature a [2 + 2]cycloaddition of the five-membered endocyclic enecarbamate 5 to alkylketenes that proceeded in high yields and with high stereoselectivity to provide an endo alkyl cycloadduct as the major or only product. The minor exo alkyl cycloadducts, which can be observed in some [2 + 2]cycloadditions, seem to derive from the endo cycloadduct, the putative kinetic product, by epimerization. An unusual regioselectivity was observed for the Baeyer-Villiger oxidation of 7-alkyl-2-azabicyclic cyclobutanones. Endo-7-alkyl cycloadducts ring-expanded exclusively to a gamma-lactone in which oxygen is inserted into the C6-C7 bond in preference to the bridgehead C5-C6 bond. With the exo-7-alkyl cycloadduct the regioselectivity of the Baeyer-Villiger oxidation is drastically reduced, leading to mixtures of regioisomeric lactones in a ratio of approximately 1.5 to 1. It is hypothesized that the steric strain built into the Criegee cyclobutane intermediate is the regioselective controlling factor in these oxidations, overriding any stereoelectronic bias for ring expansion. A rationale for the mechanism of the [2 + 2]cycloaddition involving enecarbamates and ketenes is presented, which seems to involve the participation of an N-acyliminium-enolate intermediate.


Tetralogy of Fallot: the centenary of the name. A new translation of the first of Fallot's papers.
1988 marks the centenary of the cognomen "tetralogy of Fallot". Fallot's works are often quoted and translated without mentioning that it was he who applied the noun "tetralogy" to the malformation. This new translation shows that his contribution to the morbid anatomy was not great, but he was unknowningly responsible for providing a unifying concept and a name for the commonest of all cyanotic congenital heart defects.


Expression of PD-L1 in Early-Stage Invasive Breast Carcinoma and Its Relation to Tumor-Infiltrating Lymphocytes.
Immunotherapeutic targets became one of the promising approaches in breast cancer (BC), especially in advanced stage triple-negative subtype (TNBC). However, the role of programmed cell death ligand 1 (PD-L1) targeting in other BC subtypes, especially in early-stage carcinoma is less explored. We aimed in this study to investigate the prevalence of PD-L1 in early-stage invasive BC of different molecular subtypes and to elucidate its relation to tumor-infiltrating lymphocytes (TILS) density (cytotoxic and regulatory T-cells), established clinicopathological factors and patients' outcome. One hundred and nine cases of early-stage BC were enrolled in our study. Cases were classified into five molecular subtypes according to the Immunohistochemical data. PD-L1, FOXP3 and CD8 immunostaining were analyzed for all studied cases. PD-L1 expression was correlated with CD8+ cytotoxic T-cells, FOXP3+ regulatory T-cells, histopathologic parameters, BC molecular subtypes, 7-years disease-free survival (DFS) and overall survival (OS). PD-L1 was expressed in 11% of the studied early-stage BC cases. It showed a significant correlation with high tumor grade (p= <0.001), development of metastasis (p=0.037), high FOXP3+ T-cell density (p= <0.001) and low CD8+ T-cells density (p= <0.001). PD-L1 expression was higher in TNBC (16.1%), followed by HER2/neu-enriched group (14.3%). All luminal A cases showed negative PD-L1 expression. PD-L1 was found to be an independent prognostic factor for patients' survival (DFS; p=0.031 and OS: p=0.04). Although the impact of PD-L1 on early-stage BC outcomes had not been clearly established, our results indicated that PD-L1 is a negative prognostic marker in early settings. PD-L1 can serve as a new therapeutic target for patients with high-grade early-stage breast carcinoma.


Unstimulated salivary flow and oral streptococci in pediatric patients with hematological tumors: A longitudinal study.
To evaluate the unstimulated salivary flow (USF) and salivary colonization of total Streptococcus spp. (TS) and mutans-group (MS) in pediatric patients with hematological tumors. Correlations of salivary and microbiological changes with chemotherapy and patient-related factors were also verified. Eligible children (n = 31) were evaluated before (control) and after (2, 5, and 10-weeks) the chemotherapy protocol was applied. Saliva samples were collected by the traditional spitting method to determine the USF (ml/min). Salivary TS and MS were determined by colony-forming units (CFU ) counts in a selective medium. The caries experience was evaluated by DMFT/dmft indexes. Data were submitted to Student's t-test, one-way ANOVA, and correlation tests (α = 0.05). The USF rate at baseline was 0.89 (±0.73) ml/min with up to 20% reduction during the follow-up and did not differ statistically during chemotherapy (p > .05). Chemotherapy did not modify the salivary TS load (p > .05), but induced a dysbiotic shift with higher MS counts (∼ 5 fold-increase) at 10-weeks (p < .05). There is a correlation of USF with age (r = .390) and SM load with caries experience (rs = -.540) at 5-weeks. Chemotherapy may promote a specific increase of mutans-group streptococci without changing the Streptococcus spp. load and unstimulated saliva flow. Correlation reinforced the need for further enlightenment about the chemotherapy mechanisms in the salivary and microbiological parameters.


Association of diet alone, insulin, sulfonylureas, metformin, and thiazolidinediones with the severity of coronary artery disease in patients with diabetes mellitus.
Coronary angiography was performed in 152 men and 163 women with diabetes mellitus, mean age 55 +/- 8 years, because of chest pain. Of 67 patients with 3-vessel or 4-vessel coronary artery disease (CAD), 17 (25%) were treated with diet alone, 29 (43%) with insulin, 18 (27%) with sulfonylureas, 12 (18%) with metformin, and 6 (9%) with thiazolidinediones. Of 76 patients with 2-vessel CAD, 20 (26%) were treated with diet alone, 36 (47%) with insulin, 21 (28%) with sulfonylureas, 21 (28%) with metformin, and 11 (14%) with thiazolidinediones. Of 40 patients with 1-vessel CAD, 15 (38%) were treated with diet alone, 11 (28%) with insulin, 8 (20%) with sulfonylureas, 12 (30%) with metformin, and 4 (10%) with thiazolidinediones. Of 132 patients with 0-vessel CAD, 18 (14%) were treated with diet alone, 21 (16%) with insulin, 7 (5%) with sulfonylureas, 75 (56%) with metformin, and 35 (26%) with thiazolidinediones. Cochran-Armitage trend tests were used to examine whether the use of treatment significantly increases or decreases as the number of arteries with CAD increases (P = 0.036 for diet alone; P < 0.0001 for insulin, for sulfonylureas, and for metformin; P = 0.002 for thiazolidinediones).


The Impacts of Prescribed Fire on PM2.5 Air Quality and Human Health: Application to Asthma-Related Emergency Room Visits in Georgia, USA.
Short-term exposure to fire smoke, especially particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5), is associated with adverse health effects. In order to quantify the impact of prescribed burning on human health, a general health impact function was used with exposure fields of PM2.5 from prescribed burning in Georgia, USA, during the burn seasons of 2015 to 2018, generated using a data fusion method. A method was developed to identify the days and areas when and where the prescribed burning had a major impact on local air quality to explore the relationship between prescribed burning and acute health effects. The results showed strong spatial and temporal variations in prescribed burning impacts. April 2018 exhibited a larger estimated daily health impact with more burned areas compared to Aprils in previous years, likely due to an extended burn season resulting from the need to burn more areas in Georgia. There were an estimated 145 emergency room (ER) visits in Georgia for asthma due to prescribed burning impacts in 2015 during the burn season, and this number increased by about 18% in 2018. Although southwestern, central, and east-central Georgia had large fire impacts on air quality, the absolute number of estimated ER asthma visits resulting from burn impacts was small in these regions compared to metropolitan areas where the population density is higher. Metro-Atlanta had the largest estimated prescribed burn-related asthma ER visits in Georgia, with an average of about 66 during the reporting years.


Surgically induced necrotizing scleritis after pterygium surgery with conjunctival autograft.
To report a case of surgically induced necrotizing scleritis (SINS) as a complication of conjunctival autograft after pterygium excision. A 52-year-old man had undergone nasal pterygium excision with conjunctival autograft in the right eye at another facility. He was treated for suspected infective scleritis before presentation. The sclera, at the site of prior pterygium excision, showed significant thinning with uveal show. There was active inflammation adjacent to the site of thinning. Systemic studies and the examination were noncontributory. The patient was suspected of having SINS and received pulsed injections of methylprednisolone 1000 mg/d for 3 days. The patient also underwent an emergency scleral patch graft with amniotic membrane graft. Over the next 2 weeks, the scleral graft showed vascularization and was taken well. SINS may develop after pterygium surgery with conjunctival autograft. Evidence of connective tissue disease may or may not be found on clinical examination and on laboratory studies. Early diagnosis, prompt immunosuppression, and scleral patch grafting prevents progression and further devastating complications.


Modulation of the cellular distribution of human cytomegalovirus helicase by cellular factor Snapin.
Controlled regulation of genomic DNA synthesis is a universally conserved process for all herpesviruses, including human cytomegalovirus (HCMV), and plays a key role in viral pathogenesis, such as persistent infections. HCMV UL105 is believed to encode the helicase of the DNA replication machinery that needs to localize in the nuclei, the site of viral DNA synthesis. No host factors that interact with UL105 have been identified. In this study, we show that UL105 specifically interacts with Snapin, a human protein that is predominantly localized in the cytoplasm and associated with cellular vesicles. UL105 was found to interact with Snapin in both the yeast two-hybrid screen and coimmunoprecipitation experiments in HCMV-infected cells. The nuclear and cytoplasmic levels of UL105 were decreased and increased in cells overexpressing Snapin, respectively, while the levels of UL105 in the nuclei and cytoplasm were increased and decreased in cells in which the expression of Snapin was downregulated with anti-Snapin small interfering RNA (siRNA) molecules, respectively. Furthermore, viral DNA synthesis and progeny production were decreased in cells overexpressing Snapin and increased in the anti-Snapin siRNA-treated cells, respectively. Our results provide the first direct evidence to suggest that Snapin interacts with UL105 and alters its cellular distribution, leading to modulation of viral DNA synthesis and progeny production. Our study further suggests that modulation of the cellular distribution of viral helicase by Snapin may represent a possible mechanism for regulating HCMV genomic DNA synthesis, a key step during herpesvirus lytic and persistent infections.


National plan to improve health literacy in dentistry.
Limited health literacy is associated with poorer health knowledge, worse health behaviors, and adverse clinical outcomes. In 2009, the ADA proposed a 2010-2015 strategic action plan to improve health literacy for the dental profession and other stakeholders. This article provides an overview of the National Advisory Committee on Health Literacy in Dentistry and describes the basic elements of the ADA plan.


Tunable Wettability of Electrospun Polyurethane/Silica Composite Membranes for Effective Separation of Water-in-Oil and Oil-in-Water Emulsions.
Polymer-dominated membranes with switchable wettability are highly desired due to their on-demand applications for oil/water separation. Herein, a low-cost methodology to fabricate membranes consisting of hyperbranched polyurethane (HBPU) and fluorine-modified silica (F-SiO2 ) with tunable wettability by electrospinning is reported. The HBPU/F-SiO2 composite membranes can be transformed from superhydrophobicity to -philicity through plasma treatment; these membranes exhibit different wettability for effective separation of surfactant-stabilized water-in-oil and oil-in-water emulsions.


[Multiple firearm injury caused with a blank pistol].
The authors present a case of a complex suicide of a 60-year-old woman found dead on her bed. A blank pistol Umarex caliber 9-mm, several blank cartridges and a lot of drug packages were discovered near the body. The woman suffered from a psychiatric depression. There were three gunshot wounds on the body: in the right temporal region, on the palatum of the mouth and on the left chest wall. The gunshot wounds in the right temporal region and in the mouth had central circle defects with the margins of stellate or star-like appearance and blackening. In the right temporal region the temporal muscle was contused but skull and intracranial tissues were without any injury. On the palatum of the mouth there was neither facial skeleton nor skull injury. The numerous small tears of lips and contusions of buccal mucosa were observed. On the left chest wall there was an abrasion with a bruise on the skin and contusion of thoracic muscles. Neither ribs nor intrathoracic organs were inflicted. At autopsy blood in the amount of 600 ml and a few tablets were found in the stomach as well as an insignificant blood aspiration into lungs. In spite of the fact that all the gunshot wounds were caused by shots fired at contact range they were not lethal. The woman died of lethal intoxication with tramadol and dibenzepin. Although this report differs from the ones published in literature, the authors believe that can contribute to the issue of gunshot wounds caused by gas weapons.


Fermentation of sarshir (kaymak) by lactic acid bacteria: antibacterial activity, antioxidant properties, lipid and protein oxidation and fatty acid profile.
The antioxidant and antibacterial activities of fermented sarshir (traditional dairy food), with three probiotic Lactobacillus plantarum strains (LP3, AF1, and LU5), were investigated. The oxidative stability and the lipid profile of non-fermented and fermented sarshir were compared, in addition to radical scavenging activity, as well as peroxide, anisidine and carbonyl values (PV, AnV and CV, respectively). The strong antibacterial activity of fermented sarshir against common pathogenic bacteria, including Gram-negative Escherichia coli O157: H7 ATCC 35150 and Pseudomonas aeruginosa ATCC 27853, as well as Gram-positive Bacillus cereus ATCC 10876 and Staphylococcus aureus ATCC 25923, was established. Among the strains examined, L. plantarum LP3 exhibited the highest radical scavenging activity (53.1 ± 1.8%) and lowest PV (3.0 meq kg-1 ), AnV (1.31 ± 0.06) and CV (1.4 ± 0.08). The pH of sarshir decreased from 6.2 ± 0 to 3.5 ± 0.1 during 14 h of fermentation. Incorporated bacterial cells exhibited notable viability during 10 days of cold storage (4 °C). The fermentation of sarshir by L. plantarum strains, especially LP3, resulted in beneficial changes in radical scavenging activity, as well as PV, AnV and carbonyl values, in addition to a broad spectrum of inhibitory activity against strains of P. aeruginosa, E. coli O157:H7, B. cereus and S. aureus. © 2017 Society of Chemical Industry.


Pathogenic signal peptide variants in the human genome.
Secreted and membrane proteins represent a third of all cellular proteins and contain N-terminal signal peptides that are required for protein targeting to endoplasmic reticulum (ER). Mutations in signal peptides affect protein targeting, translocation, processing, and stability, and are associated with human diseases. However, only a few of them have been identified or characterized. In this report, we identified pathogenic signal peptide variants across the human genome using bioinformatic analyses and predicted the molecular mechanisms of their pathology. We recovered more than 65 thousand signal peptide mutations, over 11 thousand we classified as pathogenic, and proposed framework for distinction of their molecular mechanisms. The pathogenic mutations affect over 3.3 thousand genes coding for secreted and membrane proteins. Most pathogenic mutations alter the signal peptide hydrophobic core, a critical recognition region for the signal recognition particle, potentially activating the Regulation of Aberrant Protein Production (RAPP) quality control and specific mRNA degradation. The remaining pathogenic variants (about 25%) alter either the N-terminal region or signal peptidase processing site that can result in translocation deficiencies at the ER membrane or inhibit protein processing. This work provides a conceptual framework for the identification of mutations across the genome and their connection with human disease.


Coexistence of primary thyroid diffuse large B cell lymphoma and papillary thyroid carcinoma in a patient with Hashimoto's thyroiditis: a case report and literature review.
Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid malignancy and also has an excellent prognosis. Primary thyroid lymphoma (PTL) is rare and has a poor prognosis. The co-occurrence of both malignancies is extremely rare, and the preoperative diagnosis is rather difficult. We report the case of a patient with both PTC and PTL in the setting of Hashimoto's thyroiditis (HT). A 59-year-old female patient was referred to our department for progressive enlargement of the thyroid gland over a few months. The imaging results demonstrated an enlarged thyroid and a mass in the thyroid. Total thyroidectomy and bilateral central neck node dissection were conducted. The final diagnosis of the coexistence of thyroid diffuse large B cell lymphoma and PTC was confirmed by histopathology and immunohistochemistry. The patient received radiation therapy and six cycles of chemotherapy combined with targeted therapy, including rituximab, cyclophosphamide, doxorubicin, vindesine, and prednisone (R-CHOP). After 6 months of follow-up, neither tumor has recurred. It is important for physicians to keep PTL in mind for differential diagnosis in HT patients with sudden thyroid enlargement.


[The phenotypes of arterial smooth-muscle cells during ontogeny and in atherosclerotic plaques].
Smooth-muscle cell (SMC) myosin expression, SMC alpha-actin, h-caldesmon and calponin expression were studied in developing SMC of embryonic aorta as well as in adult human aorta and coronary arteries. It was found that ontogenesis is associated with SMC phenotypic modulations. In 8-23-week embryos SMC express SMC myosin and alpha-actin. In adult humans arterial SMC express all the markers studied. Normal subendothelium contains a heterogeneous SMC population. SMC heterogeneity is most marked in atherosclerotic plaques in the form of clusters of homogeneous cells different by expression of contractile system proteins. It is suggested that SMC heterogeneous population in atherosclerotic plaques may arise due to proliferation of phenotypically different precursors cells.


Glucose transport rate and glycogen synthase activity both limit skeletal muscle glycogen accumulation.
We varied rates of glucose transport and glycogen synthase I (GS-I) activity (%GS-I) in isolated rat epitrochlearis muscle to examine the role of each process in determining the rate of glycogen accumulation. %GS-I was maintained at or above the fasting basal range during 3 h of incubation with 36 mM glucose and 60 microU/ml insulin. Lithium (2 mM LiCl) added to insulin increased glucose transport rate and muscle glycogen content compared with insulin alone. The glycogen synthase kinase-3beta inhibitor GF-109203 x (GF; 10 microM) maintained %GS-I about twofold higher than insulin with or without lithium but did not increase glycogen accumulation. When %GS-I was lowered below the fasting range by prolonged incubation with 36 mM glucose and 2 mU/ml insulin, raising rates of glucose transport with bpV(phen) or of %GS-I with GF produced additive increases in glycogen concentration. Phosphorylase activity was unaffected by GF or bpV(phen). In muscles of fed animals, %GS-I was approximately 30% lower than in those of fasted rats, and insulin-stimulated glycogen accumulation did not occur unless %GS-I was raised with GF. We conclude that the rate of glucose transport is rate limiting for glycogen accumulation unless %GS-I is below the fasting range, in which case both glucose transport rate and GS activity can limit glycogen accumulation.


[The Interaction of Low-dose Droperidol, Propofol, and Sevoflurane on QTc Prolongation].
Droperidol is an effective antiemetic, but its use is limited because of the warning of drug-induced QT prolongation. Some reports showed that low-dose droperidol does not significantly probing QT interval. This study was aimed to determine the effect of low-dose droperidol (1.25 and 2.5 mg) on QTc interval, and the interaction among droperidol, propofol and sevoflurane. Patients received either 1.25 mg (group L : n = 25) or 2.5 mg (group H : n = 25) droperidol, and fentanyl (3 μg x kg(-1)) was administered 2.5 min later. One minute after fentanyl administration, anesthesia was induced using propofol (1.5 mg x kg(-1)) and vecuronium. One minute after propofol administration, sevoflurane (3%) was started. Tracheal intubation was performed 3 min after propofol administration, and then sevoflurane was reduced to 1%. Compared to baseline, the QTc interval in group L was unchanged by droperidol. In group H, the QTc interval was significantly prolonged after droperidol injection, but recovered after propofol injection. After tracheal intubation, QTc interval was significantly prolonged in both groups. Droperidol's effect on QTc prolongation was shown at the dose of 2.5 mg but not 1.25 mg. This prolongation effect was offset by propofol, and was unchanged by sevoflurane.


QUANTITATIVE GENETICS OF RESPONSE TO COMPETITORS IN NEMOPHILA MENZIESII: A GREENHOUSE STUDY.
To determine the potential for adaptation to a local biotic environment, we examined the magnitude and nature of genetic variation in response to neighboring plants within a natural population of the native California annual, Nemophila menziesii. A total of 22 plants from a natural population were crossed in three reciprocal factorials. The progeny were grown in a greenhouse in nine treatments that varied in conspecific density and in the density of a naturally co-occurring grass species, Bromus diandrus. Increasing the density of each species significantly reduced individual survival, fruit number, and dry weight. Among survivors, we found small to moderate heritability of dry weight within treatments. Additive genetic correlations (rA ) of dry weight between competitive regimes were generally large and positive. In no case were they significantly different from 1, as expected under the null hypothesis that the relative performance of the genotypes under consideration is the same in all environments. On the basis of these results, we cannot conclude that the structure of genetic covariation within this population would promote genetic differentiation in response to locally varying conditions of density of these two species. Aspects of the experiment that may have compromised our ability to detect rA differing from 1 are discussed.


A metabolic and electron microscopic study of human organ-cultured cornea.
We examined the glucose metabolism and ultrastructure of human corneas stored for 11 to 37 days in organ culture using a modified Eagle's minimum essential medium. Changing the media twice weekly provided a stable pH of 7.22 to 7.28 but the glucose concentration of the media decreased from 110 mg/100 ml to 30 mg/100 ml, and lactate concentration increased from 7 mg/100 ml to 84 mg/100 ml before media replacement. The initial rate of glucose uptake and lactate release averaged 149 mug/hr and 95 mug/hr, respectively, and the rates decreased approximately 50% by day 12. The glucose uptake rate stabilized between 40 and 60% of the original rate to day 37, but the lactate release rate decreased again at day 25 from 64 to 25%. The lactate/glucose ratio averaged 65 to 82% during the first 25 days of organ culture and 33 to 53% from days 28 to 37. Electron microscopy revealed that the endothelium formed a complete monolayer of normal appearing cells covering Descemet's membrane. Intracytoplasmic deposition of glycogen granules was present in endothelial, stromal, and epithelial cells.


Uptake and specific binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the olfactory mucosa of mice and rats.
Whole-body autoradiography of mice and rats after i.v. administration of 2,3,7,8-[14C]tetrachlorodibenzo-p-dioxin ([14C]TCDD) showed a selective localization of radioactivity in the liver and nasal olfactory mucosa. In microautoradiograms of solvent extracted sections of the skulls of mice given injections of [3H]TCDD, no radioactivity was observed in the olfactory mucosa, suggesting that TCDD is not covalently bound in this tissue. The amount of specific [3H]TCDD binding sites in cytosol from the ethmoturbinates of rats (33 fmol/mg cytosolic protein) was comparable to that of the liver cytosol as estimated by electrophoresis in polyacrylamide concentration gradient gel, and therefore probably too low to explain the retention of radioactivity in the olfactory mucosa. The specific TCDD binding species in the mucosa of the ethmoturbinates exhibited a similar binding affinity for [3H]TCDD, ligand specificity, and molecular weight as the TCDD receptor from rat liver. The 7-ethoxyresorufin O-deethylase activity of the mucosa of the ethmoturbinates was induced less than twice by administration of the TCDD receptor ligand beta-naphthoflavone (5,6-benzoflavone) 40 h before killing. By administration of beta-naphthoflavone (5,6-benzoflavone) 16 h before killing, mRNA coding for cytochrome P-450d but not for cytochrome P-450c was induced to detectable levels in the mucosa of the ethmoturbinal tissue of the rat. The basal activity of 7-ethoxyresorufin O-deethylation of the mucosa of the ethmoturbinates of the rat was comparable to the corresponding activity of the liver. This basal metabolic activity of the ethmoturbinal tissue was only marginally inhibited by antibodies raised against beta-naphthoflavone (5,6-benzoflavone) induced hepatic cytochrome P-450s. Thus, enzymes other than cytochrome P-450c may possibly account for a part of the basal 7-ethoxyresorufin O-deethylase activity in the rodent olfactory mucosa.


The geriatric amputee.
There are special aspects of aging with an amputation and with being elderly at the time of an amputation. Older adults who have undergone amputation have many issues to contend with, including comorbidities that affect postoperative care and rehabilitation, general deconditioning and loss of mobility (especially if the onset of rehabilitation is delayed), and lack of social support upon returning to the community. These problems are compounded by a lack of knowledge about caring for the residual limb and prosthesis, maintenance of general health, and management of comorbid conditions. People who have sustained an amputation at an early age and who are ambulatory may find increasing difficulties as they age. Acquired chronic disease occurs more frequently as people age. These conditions can adversely affect function after amputation. Prosthetic designs may need modification because certain components may become more difficult to use. The prevention of a (second) amputation results in saving a limb and preserving self-image and independent function. Considering the emotional and economic cost of amputation and lifelong management of a prosthesis, it is worth the time and effort to practice preventive measures. Should amputation become necessary, careful patient assessment, compassionate management, and communication among the team members results in a more favorable outcome. Including the physiatrist early in the clinical course makes this process easier.


Physical Activity Questionnaires for Pregnancy: A Systematic Review of Measurement Properties.
In order to assess physical activity (PA) during pregnancy, it is important to choose the instrument with the best measurement properties. To systematically summarize, appraise, and compare the measurement properties of all self-administered questionnaires assessing PA in pregnancy. We searched PubMed, Embase, and SPORTDiscus with the following inclusion criteria: (i) the study reported at least one measurement property (reliability, criterion validity, construct validity, responsiveness) of a self-administered questionnaire; (ii) the questionnaire intended to measure PA; (iii) the questionnaire was evaluated in healthy pregnant women; and (iv) the study was published in English. We evaluated results, quality of individual studies, and quality of evidence using a standardized checklist (Quality Assessment of Physical Activity Questionnaires [QAPAQ]) and the GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach. Seventeen articles, reporting 18 studies of 11 different PA questionnaires (17 versions), were included. Most questionnaire versions showed insufficient measurement properties. Only the French and Turkish versions of the Pregnancy Physical Activity Questionnaire (PPAQ) showed both sufficient reliability and construct validity. However, all versions of the PPAQ pooled together showed insufficient construct validity. The quality of individual studies was usually high for reliability but varied considerably for construct validity. Overall, the quality of evidence was very low to moderate. We recommend the PPAQ to assess PA in pregnancy, although the pooled results revealed insufficient construct validity. The lack of appropriate standards in data collection and processing criteria for objective devices in measuring PA during pregnancy attenuates the quality of evidence. Therefore, research on the validity of comparison instruments in pregnancy followed by consensus on validation reference criteria and standards of PA measurement is needed.


Rhythmicity, synchronization and binding in human and primate motor systems.
This review focuses on recent advances in our understanding of temporal pattern coding in the motor systems of animals and man. Examples of millisecond time scale rhythmic synchronization in the visual system are considered. Results of experiments that demonstrate similar phenomena in the motor system are discussed. Finally problems concerning the nature of the correlation between neurophysiological signals and the relationship of correlation to motor behaviour are explored.


Structure of glutaraldehyde cross-linked ryanodine receptor.
The ryanodine receptor (RyR) family of calcium release channels plays a vital role in excitation-contraction coupling (ECC). Along with the dihydropyridine receptor (DHPR), calsequestrin, and several other smaller regulatory and adaptor proteins, RyRs form a large dynamic complex referred to as ECC machinery. Here we describe a simple cross-linking procedure that can be used to stabilize fragile components of the ECC machinery, for the purpose of structural elucidation by single particle cryo-electron microscopy (cryo-EM). As a model system, the complex of the FK506-binding protein (FKBP12) and RyR1 was used to test the cross-linking protocol. Glutaraldehyde fixation led to complete cross-linking of receptor-bound FKBP12 to RyR1, and also to extensive cross-linking of the four subunits comprising RyR to one another without compromising the RyR1 ultrastructure. FKBP12 cross-linked with RyR1 was visualized in 2D averages by single particle cryo-EM. Comparison of control RyR1 and cross-linked RyR1 3D reconstructions revealed minor conformational changes at the transmembrane assembly and at the cytoplasmic region. Intersubunit cross-linking enhanced [(3)H]ryanodine binding to RyR1. Based on our findings we propose that intersubunit cross-linking of RyR1 by glutaraldehyde induced RyR1 to adopt an open like conformation.


Differentiation of promyelocytic leukemia cells HL-60 induced by daidzein in vitro and in vivo.
We have screened more than one thousand synthetic and natural chemicals to explore differentiation inducers and found that daidzein has potent differentiation-inducing activity for human leukemia HL-60 cells, both in vitro and in vivo. In vitro study showed that daidzein at concentrations exceeding 10 micrograms/ml caused inhibition of HL-60 cells; and it induced differentiation of the cells into granulocytic lineage as judged by NBT reduction activity, phagocytic ability and morphological characteristics. Flow cytometry study indicated that daidzein arrested HL-60 cells in the G1 phase. The growth of HL-60 cells in the subrenal capsules of mice and in diffusion chambers implanted into the peritoneal cavities of mice was inhibited by 50 mg/kg daidzein. HL-60 cells treated with daidzein in vivo also exhibited characteristic morphological changes of matured cells. Moreover, the colony forming efficiency of HL-60 cells in diffusion chambers in mice was markedly inhibited by the administration of daidzein.


Efficacy and safety of eslicarbazepine acetate versus controlled-release carbamazepine monotherapy in newly diagnosed epilepsy: A phase III double-blind, randomized, parallel-group, multicenter study.
We assessed the efficacy and safety of once-daily eslicarbazepine acetate in comparison with twice-daily (BID) controlled-release carbamazepine (carbamazepine-CR) monotherapy in newly diagnosed focal epilepsy patients. This randomized, double-blind, noninferiority trial (NCT01162460) utilized a stepwise design with 3 dose levels. Patients who remained seizure-free for the 26-week evaluation period (level A: eslicarbazepine acetate 800 mg/carbamazepine-CR 200 mg BID) entered a 6-month maintenance period. If a seizure occurred during the evaluation period, patients were titrated to the next target level (level B: eslicarbazepine acetate 1200 mg/carbamazepine-CR 400 mg BID, level C: eslicarbazepine acetate 1600 mg/carbamazepine-CR 600 mg BID) and the evaluation period began again. The primary endpoint was the proportion of seizure-free patients for 6 months after stabilization in the per protocol set. The predefined noninferiority criteria were -12% absolute and -20% relative difference between treatment groups. Eight hundred fifteen patients were randomly assigned; 785 (388 in the eslicarbazepine acetate group and 397 in the carbamazepine-CR group) were included in the per protocol set, and 813 (401 in the eslicarbazepine acetate group and 412 in the carbamazepine-CR group) were included in the full analysis set for the primary analysis. Overall, 71.1% of eslicarbazepine acetate-treated patients and 75.6% of carbamazepine-CR-treated patients were seizure-free for ≥6 months at the last evaluated dose (average risk difference = -4.28%, 95% confidence interval [CI] = -10.30 to 1.74; relative risk difference = -5.87%, 95% CI = -13.50 to 2.44) in the per protocol set. Rates of treatment-emergent adverse events were similar between groups for patients in the safety set. Noninferiority was also demonstrated in the full analysis set, as 70.8% of patients with eslicarbazepine acetate and 74.0% with carbamazepine-CR were seizure-free at the last evaluated dose (average risk difference = -3.07, 95% CI = -9.04 to 2.89). Treatment with eslicarbazepine acetate was noninferior to BID carbamazepine-CR. With its once-daily formulation, eslicarbazepine acetate provides a useful option for first-line monotherapy for adults with newly diagnosed epilepsy and focal onset seizures.


Granulocyte colony-stimulating factor attenuates neuronal death and promotes functional recovery after spinal cord injury in mice.
Granulocyte colony-stimulating factor (G-CSF) is a protein that stimulates differentiation, proliferation, and survival of granulocytic lineage cells. Recently, a neuroprotective effect of G-CSF was reported in a model of cerebral infarction. The aim of the present study was to elucidate the potential therapeutic effect of G-CSF for spinal cord injury (SCI) in mice. We found that G-CSF is neuroprotective against glutamate-induced cell death of cerebellar granule neurons in vitro. Moreover, we used a mouse model of compressive SCI to examine the neuroprotective potential of G-CSF in vivo. Histologic assessment with cresyl violet staining revealed that the number of surviving neurons in the injured spinal cord was significantly increased in G-CSF-treated mice. Immunohistochemistry for neuronal apoptosis revealed that G-CSF suppressed neuronal apoptosis after SCI. Moreover, administration of G-CSF promoted hindlimb functional recovery. Examination of signaling pathways downstream of the G-CSF receptor suggests that G-CSF might promote functional recovery by inhibiting neuronal apoptosis after SCI. G-CSF is currently used in the clinic for hematopoietic stimulation, and its ongoing clinical trial for brain infarction makes it an appealing molecule that could be rapidly placed into trials for patients with acute SCI.


Pathways linking ethnic discrimination and drug-using peer affiliation to underage drinking status among Mexican-origin adolescents.
Using a three-wave longitudinal data set of Mexican-origin adolescents (N = 602, Mage = 12.92, SD = 0.91 at Wave 1), this study examines parallel pathways from early exposure to ethnic discrimination and drug-using peers, separately, to underage drinking status by late adolescence. Negative affect was expected to mediate the link from ethnic discrimination to underage drinking status (the stress-induced pathway), whereas social alcohol expectancy was expected to mediate the link from drug-using peers to underage drinking status (the socialization pathway). Our findings lend support to the stress-induced pathway while controlling for the socialization pathway. For the stress-induced pathway, we found that early ethnic discrimination experiences were related to higher likelihood of having engaged in underage drinking by late adolescence through elevated negative affect sustained across adolescence. For the socialization pathway, we found no association between affiliation with drug-using peers in early adolescence and underage drinking status, either directly or indirectly. Present findings highlight the unique role of early ethnic discrimination experiences in underage drinking among Mexican-origin adolescents, over and above the effect of drug-using peers. Alcohol use interventions targeting ethnic minority adolescents should account for adolescents' ethnic discrimination experiences by helping adolescents develop adaptive coping strategies to handle negative affect induced by discrimination (e.g., reappraisal) rather than using alcohol to self-medicate. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Immune System Activation and Depression: Roles of Serotonin in the Central Nervous System and Periphery.
Serotonin (5-hydroxytryptamine, 5-HT) has long been recognized as a key contributor to the regulation of mood and anxiety and is strongly associated with the etiology of major depressive disorder (MDD). Although more known for its roles within the central nervous system (CNS), 5-HT is recognized to modulate several key aspects of immune system function that may contribute to the development of MDD. Copious amounts of research have outlined a connection between alterations in immune system function, inflammation status, and MDD. Supporting this connection, peripheral immune activation results in changes in the function and/or expression of many components of 5-HT signaling that are associated with depressive-like phenotypes. How 5-HT is utilized by the immune system to effect CNS function and ultimately behaviors related to depression is still not well understood. This Review summarizes the evidence that immune system alterations related to depression affect CNS 5-HT signaling that can alter MDD-relevant behaviors and that 5-HT regulates immune system signaling within the CNS and periphery. We suggest that targeting the interrelationships between immune and 5-HT signaling may provide more effective treatments for subsets of those suffering from inflammation-associated MDD.


Composition- and Structure-Tunable Gold-Cobalt Nanoparticles and Electrocatalytic Synergy for Oxygen Evolution Reaction.
The increasing energy crisis constitutes an inspiring drive seeking alternative energies such as hydrogen from water splitting which is clean and abundant, but a key challenge for water splitting is the need of highly efficient catalysts for oxygen evolution reaction (OER). This report describes findings of an investigation of the synthesis of gold-cobalt (AuCo) nanoparticles by a facile one-pot and injection method and their use as highly efficient catalysts for OER. While particle size depends on the synthesis method, the composition of the nanoparticles is controlled by feeding ratio of Au and Co precursors in the synthesis. Depending on Co content, the nanoparticles exhibit largely phase-segregated domains with a core (Au)-shell (Co) type of structure at a high level of Co. Upon the thermochemical treatment of carbon-supported AuCo nanoparticles, the redox activity of Co species in the nanoparticles with cycle number is shown to decrease which changes the surface oxidation state of Co species without changing the composition significantly. The electrocatalytic activity for OER in alkaline electrolytes is shown to depend on the bimetallic composition, displaying a maximum activity for an Au:Co ratio of ∼2:3. This dependence is also shown to correlate with the surface oxidation state and redox activities, providing an insight into the electrocatalytic activity. Mechanistic aspects of the electrocataltytic properties are discussed in terms of the bifunctional synergy of Co and Au in the nanoparticle catalysts.


European invasion of North American Pinus strobus at large and fine scales: high genetic diversity and fine-scale genetic clustering over time in the adventive range.
North American Pinus strobus is a highly invasive tree species in Central Europe. Using ten polymorphic microsatellite loci we compared various aspects of the large-scale genetic diversity of individuals from 30 sites in the native distribution range with those from 30 sites in the European adventive distribution range. To investigate the ascertained pattern of genetic diversity of this intercontinental comparison further, we surveyed fine-scale genetic diversity patterns and changes over time within four highly invasive populations in the adventive range. Our data show that at the large scale the genetic diversity found within the relatively small adventive range in Central Europe, surprisingly, equals the diversity found within the sampled area in the native range, which is about thirty times larger. Bayesian assignment grouped individuals into two genetic clusters separating North American native populations from the European, non-native populations, without any strong genetic structure shown over either range. In the case of the fine scale, our comparison of genetic diversity parameters among the localities and age classes yielded no evidence of genetic diversity increase over time. We found that SGS differed across age classes within the populations under study. Old trees in general completely lacked any SGS, which increased over time and reached its maximum in the sapling stage. Based on (1) the absence of difference in genetic diversity between the native and adventive ranges, together with the lack of structure in the native range, and (2) the lack of any evidence of any temporal increase in genetic diversity at four highly invasive populations in the adventive range, we conclude that population amalgamation probably first happened in the native range, prior to introduction. In such case, there would have been no need for multiple introductions from previously isolated populations, but only several introductions from genetically diverse populations.


Hydrogen bond ordering in ice V and the transition to ice XIII.
The proton ordered version of ice V, ice XIII, was recently identified using Raman spectroscopy and neutron diffraction techniques. The transformation, between 108 and 117 K, only occurred in the presence of a small amount of dopant, similar to the proton ordering transition of ice Ih/XI. In this work, we investigate the hydrogen bond fluctuations in ice V and XIII with statistical mechanical techniques that use results from periodic electronic density functional theory calculations as input. We find a number of low-lying hydrogen bond configurations, approximately 20 within 10 K/water above the ground state state configuration, the structure of which agrees with fully ordered ice XIII. Using an analytic theory, graph invariants, we developed effective spin-lattice Hamiltonians governing hydrogen bond fluctuations to perform statistical mechanical calculations for a large simulation cell containing 6048 water molecules. Two models were constructed, one more elaborate than the first, to gauge the robustness of our methods when the unit cell is very complex and a large number of configurations lie close in energy to the ground state. The predicted proton ordering transitions, 62 and 72 K for the two models, are in qualitative agreement with experiment. Occupation probabilities, obtained from our simulations, compare well with values from recent neutron diffraction experiments and help verify our effective Hamiltonians. In both models, we find that a second order phase transition intervenes about 10 K above the transition to ice XIII, but its effect is negligible on the behavior of thermodynamic functions near the transition to ice XIII.


A Novel Soybean Dirigent Gene GmDIR22 Contributes to Promotion of Lignan Biosynthesis and Enhances Resistance to Phytophthora sojae.
Phytophthora root and stem rot caused by the oomycete pathogen Phytophthora sojae is a destructive disease of soybean worldwide. Plant dirigent proteins (DIR) are proposed to have roles in biosynthesis of either lignan or lignin-like molecules, and are important for defense responses, secondary metabolism, and pathogen resistance. In the present work, a novel DIR gene expressed sequence tag is identified as up-regulated in the highly resistant soybean cultivar 'Suinong 10' inoculated with P. sojae. The full length cDNA is isolated using rapid amplification of cDNA ends, and designated GmDIR22 (GenBank accession no. HQ_993047). The full length GmDIR22 is 789 bp and contains a 567 bp open reading frame encoding a polypeptide of 188 amino acids. The sequence analysis indicated that GmDIR22 contains a conserved dirigent domain at amino acid residues 43-187. The quantitative real-time reverse transcription PCR demonstrated that soybean GmDIR22 mRNA is expressed most highly in stems, followed by roots and leaves. The treatments with stresses demonstrated that GmDIR22 is significantly induced by P. sojae and gibberellic acid (GA3), and also responds to salicylic acid, methyl jasmonic acid, and abscisic acid. The GmDIR22 is targeted to the cytomembrane when transiently expressed in Arabidopsis protoplasts. Moreover, The GmDIR22 recombinant protein purified from Escherichia coli could effectively direct E-coniferyl alcohol coupling into lignan (+)-pinoresinol. Accordingly, the overexpression of GmDIR22 in transgenic soybean increased total lignan accumulation. Moreover, the lignan extracts from GmDIR22 transgenic plants effectively inhibits P. sojae hyphal growth. Furthermore, the transgenic overexpression of GmDIR22 in the susceptible soybean cultivar 'Dongnong 50' enhances its resistance to P. sojae. Collectively, these data suggested that the primary role of GmDIR22 is probably involved in the regulation of lignan biosynthesis, and which contributes to resistance to P. sojae.


Experimental infection of emus (Dromaiius novaehollandiae) with avian influenza viruses of varying virulence: clinical signs, virus shedding and serology.
Two groups of emus were experimentally inoculated with a low and high pathogenic strain of avian influenza virus (AIV), type A to determine the virus susceptibility, pathogenicity, shedding and seroconversion. Emus were found susceptible to infection with AIV, with virus shedding detectable in tracheal and cloacal swabs between 3 and 10 days post-infection. Only the birds infected with the highly pathogenic viral isolate showed a brief period of mild clinical signs associated with infection. Virus recovered from the infected emus was found to be of similar pathogenicity to that of the virus inoculum. All the birds seroconverted by 10 days post-infection, as determined by haemagglutination inhibition, agar gel immunodiffusion and competitive ELISA assays. This study suggests that emus are similar to wild waterfowl in their response to AIV infection, in that they are susceptible and will replicate and shed the virus, but do not show any marked clinical signs of infection.


Becoming their mother: Knowledge, attitudes, and practices of orphanage personnel in Ukraine.
Institutional caregiving can have adverse effects on children, yet little is known about the caregivers of institutionalized young children. We surveyed staff in three Ukrainian Baby Homes about their attitudes toward the nature of their work and the needs of the young children in their care. Seventy-one caregivers completed anonymous, semistructured surveys. Popular reasons for working in Baby Homes included benefits and convenient work shifts, morality, and affection for children. Caregivers reported both favorable aspects of the work (enjoyment of children, professional satisfaction) and work difficulties (conflicts, lack of cooperation, little administrative support). In addition, they noted deficiencies in care: high caregiver-child ratio, frequent care disruptions, and lack of stimulation. Direct caregivers (in-room "nannies," educators, and nurses) and other providers (e.g., clinic nurses, physicians, therapists) differed in university-degree attainment, professional motivation, enjoyment of children, professional satisfaction, and perceptions of self as substitute mother. A number of potential "windows for change" were identified, including recognition of deficiencies in institutional care and possibilities for improvement. Implications for interventions are discussed, including the need to consider lack of staff support, high emotional stress, internal conflicts, beliefs and attitudes about institutionalized children and their biological parents, and differences in staff educational achievement.