Inhibition of arginine ADP-ribosyltransferase 1 reduces the expression of poly(ADP-ribose) polymerase-1 in colon carcinoma.
Poly(ADP-ribose) polymerase-1 (PARP-1) which mediates poly-ADP-ribosylation, has been extensively investigated in carcinoma compared to arginine ADP-ribosyltransferase 1 (ART1), which mediates mono‑ADP‑ribosylation. Previous studies have demonstrated that these enzymes promote proliferation and tumor development in colon carcinoma. However, whether there is any association between PARP-1 and ATR1 in colon carcinoma, remains unelucidated. In this study, using immunohistochemical analysis, we detected a higher expression of PARP-1 and ART1 in 63 samples from patients with colon carcinoma compared to 10 samples of normal colonic mucosa; our results revealed a positive correlation between the expression of PARP-1 and ART1 in the 63 human colon carcinoma tissue samples. To determine the correlation between PARP-1 and ART1, inhibitors of PARP-1 and ART1 and lentivirus vector‑mediated ART1 short‑hairpin RNA (shRNA) were used to culture CT26 murine colon adenocarcinoma cells separately. Using double‑label immunofluorescence assay, we detected the expression of PARP-1 in the CT26 cells, which was decreased following treatment with 5‑aminoisoquinolinone (5-AIQ, a PARP-1 inhibitor) or meta‑iodobenzylguanidine (MIBG, an ART1 inhibitor). However, the expression of ART1 only decreased when the CT26 cells were treated with MIBG. Furthermore, our results demonstrated that silencing ART1 inhibited PARP‑1 expression by decreasing the expression of nuclear factor-κB (NF-κB), inhibiting ras homolog A (RhoA). Hence, our data demonstrate the positive correlation between ART1 and PARP-1; the inhibition of ART1 activity downregulates PARP-1 expression by decreasing the activity of NF-κB in CT26 colon carcinoma cells.


Treatment of stage III non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.
Stage III non-small cell lung cancer (NSCLC) describes a heterogeneous population with disease presentation ranging from apparently resectable tumors with occult microscopic nodal metastases to unresectable, bulky nodal disease. This review updates the published clinical trials since the last American College of Chest Physicians guidelines to make treatment recommendations for this controversial subset of patients. Systematic searches were conducted through MEDLINE, Embase, and the Cochrane Database for Systematic Review up to December 2011, focusing primarily on randomized trials, selected meta-analyses, practice guidelines, and reviews. For individuals with stage IIIA or IIIB disease, good performance scores, and minimal weight loss, treatment with combined chemoradiotherapy results in better survival than radiotherapy alone. Consolidation chemotherapy or targeted therapy following definitive chemoradiation for stage IIIA is not supported. Neoadjuvant therapy followed by surgery is neither clearly better nor clearly worse than definitive chemoradiation. Most of the arguments made regarding patient selection for neoadjuvant therapy and surgical resection provide evidence for better prognosis but not for a beneficial impact of this treatment strategy; however, weak comparative data suggest a possible role if only lobectomy is needed in a center with a low perioperative mortality rate. The evidence supports routine platinum-based adjuvant chemotherapy following complete resection of stage IIIA lung cancer encountered unexpectedly at surgery. Postoperative radiotherapy improves local control without improving survival. Multimodality therapy is preferable in most subsets of patients with stage III lung cancer. Variability in the patients included in randomized trials limits the ability to combine results across studies and thus limits the strength of recommendations in many scenarios. Future trials are needed to investigate the roles of individualized chemotherapy, surgery in particular cohorts or settings, prophylactic cranial radiation, and adaptive radiation.


HIV testing and awareness of care-related services among a group of HIV-positive Asian Americans and Pacific Islanders in the United States: findings from a supplemental HIV/AIDS surveillance project.
Compared with other racial/ethnic groups in the United States, Asian Americans and Pacific Islanders (AAPIs) are more likely to be at an advanced stage of AIDS disease and have opportunistic infections at the time of diagnosis. However, it is not clear how these two findings are related to issues such as HIV testing and access to HIV care-related services. We examined HIV testing and awareness of care-related services among a group of HIV-positive AAPIs in the United States. Data are from a multisite supplemental surveillance project, 1990-1999. Compared with Whites, a higher percentage of AAPIs cited "illness" as the main reason for HIV testing and had their tests done as a hospital inpatients--although these differences were not statistically significant. A significantly lower percentage of AAPIs than Whites were aware of their current CD4 count; AAPIs also had significantly lower awareness about a number of care-related services. Among AAPIs, educational level was positively associated with awareness of these services. Efforts are needed to promote service availability among HIV-positive AAPIs.


The Search for Potent, Small-Molecule HDACIs in Cancer Treatment: A Decade After Vorinostat.
Histone deacetylases (HDACs) play a crucial role in the remodeling of chromatin, and are involved in the epigenetic regulation of gene expression. In the last decade, inhibition of HDACs came out as a target for specific epigenetic changes associated with cancer and other diseases. Until now, more than 20 HDAC inhibitors (HDACIs) have entered clinical studies, and some of them (e.g., vorinostat, romidepsin) have been approved for the treatment of cutaneous T-cell lymphoma. This review provides an overview of current knowledge, progress, and molecular mechanisms of HDACIs, covering a period from 2011 until 2015.


Electrowetting of aligned carbon nanotube films.
Electrowetting is one approach to reducing the interfacial tension between a solid and a liquid. In this method, an electrical potential is applied across the solid/liquid interface which modifies the wetting properties of the liquid on the solid without changing the composition of the solid and liquid phases. Electrowetting of aligned carbon nanotube (CNT) films is investigated by the sessile drop method by dispensing deionized (DI) water or 0.03 M NaCl droplets (contacted by Au wire) onto aligned CNT films assembled on a copper substrate. The results demonstrate that electrowetting can greatly reduce the hydrophobicity of the aligned CNTs; the contact angle saturation for DI water and 0.03 M NaCl droplets occurs at 98 and 50 degrees , respectively. The combined effects of the geometrical roughness and the electrical potential on the contact angle are briefly discussed and modeled. Such a strategy may be invoked to controllably reduce the interfacial tension between carbon nanotubes (CNTs) and polymer precursors when infiltrating the monomers into the prealigned nanotube films.


Phosphodiesterase-4 inhibitor therapy for lung diseases.
Phosphodiesterases (PDEs) are a superfamily of enzymes that catalyze the breakdown of cAMP and/or cyclic guanosine monophosphate (GMP) to their inactive form. PDE4 is the main selective cAMP-metabolizing enzyme in inflammatory and immune cells. Because PDE4 is highly expressed in leukocytes and other inflammatory cells involved in the pathogenesis of inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), inhibition of PDE4 has been predicted to have an antiinflammatory effect and thus therapeutic efficacy. The limited and inconsistent efficacy and side effects of the early compounds made their further development less desirable in asthma, given the excellent efficacy/tolerability ratio of inhaled steroids. The lack of effective antiinflammatory drug treatment for COPD has thus shifted the interest in development toward COPD. Roflumilast, the only PDE4 inhibitor that has reached the market because of the good efficacy/tolerability ratio, is recommended for patients with COPD with severe airflow limitation, symptoms of chronic bronchitis, and a history of exacerbations, whose disease is not adequately controlled by long-acting bronchodilators. Albeit safe, it maintains significant side effects (diarrhea, nausea, weight loss) that make it intolerable in some patients. Future developments of PDE4 inhibitors include extended indications of roflumilast (1) in patients with COPD, and (2) in other respiratory (e.g., asthma) and nonrespiratory chronic inflammatory/metabolic conditions (e.g., diabetes), as well as (3) the development of new molecules with PDE4 inhibitory properties with an improved efficacy/tolerability profile.


Glucosyl Zeatin and Glucosyl Ribosylzeatin from Vinca rosea L. Crown Gall Tumor Tissue.
Recently detected but unidentified cytokinin activity in crown gall tumor tissue from Vinca rosea L. grown on media containing sources of reduced nitrogen has now been attributed to two adenine-type cytokinins. These compounds are glucopyranosyl derivatives of zeatin and ribosylzeatin. The substitution in each case is on the isopentenyl chain of the parent compound. Neither of these compounds had activity in the soybean callus bioassay at concentrations lower than 1 nm whereas zeatin had activity at 0.1 nm.


Endoscopic resection for non-polypoid dysplasia in inflammatory bowel disease: a systematic review protocol.
Non-polypoid low-grade dysplasia in inflammatory bowel disease is associated with a medium increased risk of colorectal cancer, while treatment recommendations remain controversial. We aim to evaluate the efficacy and safety of endoscopic treatment for non-polypoid dysplasia in patients with inflammatory bowel disease. Medline, Embase, Cochrane Library, Scopus, Web of Science and clinical trials registry from database inception to the search date will be used to retrieve eligible studies. Studies that report the curative resection rate or any of other secondary outcomes of endoscopic treatment in patients with non-polypoid dysplasia in inflammatory bowel disease will be included in the analysis. We will conduct quantitative synthesis if the eligible studies are homogeneous judging from clinical and methodological perspectives. Ethical approval for this study was waived by the Ethics Committee of Peking Union Medical College Hospital because there are no individual data involved in the analysis and all the combined results will be retrieved from study-level data. We plan to disseminate results through peer-reviewed journals or conference abstracts. CRD42019120413.


Milk proteins in the etiology of insulin-dependent diabetes mellitus (IDDM).
The etiology of insulin-dependent diabetes mellitus (IDDM) is multifactorial. The final cause of the disease, the specific destruction of the islet beta-cells, is the result of a cellular/humoral autoimmune process that operates in individuals with a particular genetic background in response to an external triggering factor(s). The most likely environmental triggers are virus infections and dietary factors. Among the latter group dietary proteins, mainly cow milk proteins, have been found to be important. Elimination of intact cow milk proteins from the diet significantly reduced the incidence of IDDM in the spontaneously diabetic BB rat, the elimination being most effective when it occurs during the pre-weaning period. Conversely, in newly discovered diabetics (both rats and children) increased levels of antibodies to cow milk proteins as compared with non-diabetic controls were found. These higher titres of antibodies were against beta-lactoglobulin and anti-bovine serum albumin. In further studies we found that antibodies to bovine serum albumin cross-react with a beta-cell membrane protein of Mr 69,000 and that this protein is likely induced by interferon. At the molecular level, a region of the bovine serum albumin has distinct homology to the beta-subunits of the MHC class II proteins Ia, DQ and DR, and antibodies raised against this bovine serum albumin region identified the same 69K beta cell membrane protein, in the same manner as antibodies to the third hypervariable region of DR-beta did. Our hypothesis is that bovine milk proteins (mainly bovine serum albumin) might be an important environmental factor providing specific peptides that share antigenic epitopes with host cell proteins.(ABSTRACT TRUNCATED AT 250 WORDS)


Antitumor agents 68: effects of a series of helenalin derivatives on P-388 lymphocytic leukemia nucleic acid and protein synthesis.
A series of analogues related to helenalin demonstrated moderate capability for inhibiting the growth of murine P-388 lymphocytic leukemia cells in vivo and in vitro. The growth inhibition correlated with suppression of both DNA and protein synthesis in P-388 cells. The inhibition of protein synthesis occurred at a relatively low concentration and appeared to occur at the level of initiation. The suppression of DNA synthesis in P-388 cells correlated positively with inhibition of inosine 5'-monophosphate dehydrogenase activity. Although nuclear and alpha DNA polymerase activities were suppressed by certain analogues, the inhibition of the polymerases did not correlate positively with DNA synthesis inhibition and, furthermore, the magnitude of suppression of DNA polymerase activity did not appear to be sufficient to account for the observed suppression of DNA synthesis in P-388 cells.


Features, State and Context of Narcissism in Drug Misuse.
Both clinical and street-based encounters with people who misuse drugs have led the authors to examine the relationship between misuse of drugs and narcissism. Widely accepted criteria for diagnosing Substance Use Disorder (SUD) suggest parallels between narcissistic traits (e.g. invulnerability to consequences and lack of empathy for others) and the characteristics of drug abusers. Because narcissism as a concept has a long and somewhat confusing history, we first reviewed its origins in the psychoanalytic tradition of psychiatry and its exegesis into current clinical concepts in order to arrive at a set of attributes that may be useful when applied to problems of drug abuse. This process required extensive review of the literature on narcissism and its interactions with the literature on drug abuse. This process led to an understanding that positive self-concept may exemplify a variety of socially beneficial narcissism, but that at the other end of narcissism's continuum of traits may be found exploitative and non-empathetic traits. Furthermore, the negative traits of narcissism, as they may arise in adolescence along with drug use, can support an individual's ongoing dependence on drugs, especially if narcissism and drug use persist into adulthood. Our investigation of narcissism and drug use revealed, through in-depth interviewing, that some drug users employ drugs and alcohol to feed their self-concepts of superiority over other people. Our findings suggest that treatment for drug abuse cannot proceed assuming that drug users have low self-concepts. Rather, their continued use of drugs may emanate from a narcissistic sense of superiority.


[Physiology and pathophysiology of visceral pain].
Visceral pain is diffusely localized, referred to deep somatic tissues, skin and viscera, frequently not correlated with an actual trauma, commonly correlated with strong negative affective reactions and accompanied by strong protective autonomic and motor reactions. It is correlated with the excitation of spinal (thoraco-lumbar, sacral) visceral afferents and (with a few exceptions) not with the excitation of vagal afferents. Spinal visceral afferents are polymodal and can be excited by physical and chemical stimuli. All groups of visceral afferents can be sensitized (e.g.by inflammation). Normally silent (mechanically insensitive) visceral afferents are recruited by inflammation. Individual visceral afferent neurons project in laminae I and V of the dorsal horn over several segments, medio-lateral over the entire width of the dorsal horn and to the contralateral side. Their activity is synaptically transmitted, in these and deeper laminae, to viscero-somatic convergent neurons which receive additional afferent synaptic input from skin and deep somatic tissues of the corresponding dermatomes,myotomes and sclerotomes. The mechanism of sensitization of viscerosomatic convergent neurons (central sensitization) during sensitization of spinal visceral afferents is unclear.Viscero-somatic tract neurons project to lower and upper brain stem,hypothalamus and via the thalamus to various cortex areas. Visceral nociception and pain is presumably (together with other visceral sensations and homeostatic regulations of autonomic body functions) primarily represented in the insula in the context of interoception. The insula obtains its main peripheral afferent input from lamina I neurons via the Nucleus ventromedialis posterior of the thalamus. The transmission of visceral impulses in the spinal cord is modulated by the endogenous control systems in the brain stem which are in turn under the control of cortex and limbic system.


Gas Exchange Characteristics of the Submerged Aquatic Crassulacean Acid Metabolism Plant, Isoetes howellii.
The submerged aquatic plant Isoetes howellii Engelmann possesses Crassulacean acid metabolism (CAM) comparable to that known from terrestrial CAM plants. Infrared gas analysis of submerged leaves showed Isoetes was capable of net CO(2) uptake in both light and dark. CO(2) uptake rates were a function of CO(2) levels in the medium. At 2,500 microliters CO(2) per liter (gas phase, equivalent to 1.79 milligrams per liter aqueous phase), Isoetes leaves showed continuous uptake in both the light and dark. At this CO(2) level, photosynthetic rates were light saturated at about 10% full sunlight and were about 3-fold greater than dark CO(2) uptake rates. In the dark, CO(2) uptake rates were also a function of length of time in the night period. Measurements of dark CO(2) uptake showed that, at both 2,500 and 500 microliters CO(2) per liter, rates declined during the night period. At the higher CO(2) level, dark CO(2) uptake rates at 0600 h were 75% less than at 1800 h. At 500 microliters CO(2) per liter, net CO(2) uptake in the dark at 1800 h was replaced by net CO(2) evolution in the dark at 0600 h. At both CO(2) levels, the overnight decline in net CO(2) uptake was marked by periodic bursts of accelerated CO(2) uptake. CO(2) uptake in the light was similar at 1% and 21% O(2), and this held for leaves intact as well as leaves split longitudinally. Estimating the contribution of light versus dark CO(2) uptake to the total carbon gain is complicated by the diurnal flux in CO(2) availability under field conditions.


Physical characterization of whole and skim dried milk powders.
The lack of updated knowledge about the physical properties of milk powders aimed us to evaluate selected physical properties (water activity, particle size, density, flowability, solubility and colour) of eleven skim and whole milk powders produced in Europe. These physical properties are crucial both for the management of milk powder during the final steps of the drying process, and for their use as food ingredients. In general, except for the values of water activity, the physical properties of skim and whole milk powders are very different. Particle sizes of the spray-dried skim milk powders, measured as volume and surface mean diameter were significantly lower than that of the whole milk powders, while the roller dried sample showed the largest particle size. For all the samples the size distribution was quite narrow, with a span value less than 2. The loose density of skim milk powders was significantly higher than whole milk powders (541.36 vs 449.75 kg/m3). Flowability, measured by Hausner ratio and Carr's index indicators, ranged from passable to poor when evaluated according to pharmaceutical criteria. The insolubility index of the spray-dried skim and whole milk powders, measured as weight of the sediment (from 0.5 to 34.8 mg), allowed a good discrimination of the samples. Colour analysis underlined the relevant contribution of fat content and particle size, resulted in higher lightness (L*) for skim milk powder than whole milk powder, which, on the other hand, showed higher yellowness (b*) and lower greenness (-a*). In conclusion a detailed knowledge of functional properties of milk powders may allow the dairy to tailor the products to the user and help the food processor to perform a targeted choice according to the intended use.


Dietary nutrient intakes and slight albuminuria in people at least 40 years old.
We studied the relation between diet and slight albuminuria in 5416 people, ages 40 years and over, who participated in a health screening survey of a local workforce. Degree of albuminuria showed log-linear univariate relations with dietary protein, cholesterol, and sodium intakes, and negative log-linear univariate relations with dietary fiber and polyunsaturated to saturated fat (P/S) ratio. After adjusting for age, gender, and ethnicity, the relative risk (95% confidence interval) for slight albuminuria was significantly increased in people reporting dietary cholesterol consumption > 226 mg/day compared with people reporting consumption < or = 226 mg/day [1.32 (1.02, 1.70)], and significantly reduced in people reporting dietary fiber consumption > 26 g/day compared with people reporting consumption < or = 26 g/day [0.74 (0.58, 0.95)]. There was no significant effect of dietary protein, P/S ratio, or salt intake. We conclude that risk of slight albuminuria is increased by consumption of dietary cholesterol and reduced by consumption of dietary fiber.


International labor migration in the Middle East: a review of literature and research, 1974-84.
"This article reviews the main trends in the literature and research on international labor migration in the Middle East over the period 1974-84. This literature, which is characterized as descriptive and judgemental, falls into three broad categories: first, international and national overviews of migration trends, remittance flows and their macro-economic impact; second, descriptions of government policies designed to organize and regulate labor migration; third, at the community and household scale, comparative studies of migrant and non-migrant behavior in labor-sending countries."


Physicians' reliance on specialists, therapists, and vendors when prescribing therapies and durable medical equipment for children with special health care needs.
Physicians who care for children with special (health care) needs (CWSN) often must prescribe therapies and/or specialized, durable medical equipment (DME). Given this responsibility and the increasing scrutiny of prescribing practices by various oversight agencies, understanding the extent to which pediatricians rely on their own expertise when prescribing therapies and DME is an important area of research. As part of an ongoing investigation of physician preparedness for and practice in prescribing therapies, DME, or procedures for CWSN, we mailed surveys to practicing pediatricians in each of 2 states-Ohio and Mississippi-and to a senior resident at all identified pediatric residency-training programs. The surveys polled recipients as to who they would rely on themselves-specialists, therapists or vendors-to make prescription decisions for a variety of therapies and DME of increasing complexity. We report results as proportions of returned and completed questionnaires. Comparisons among the 3 groups (pediatricians from Ohio and Mississippi and residents) were made with the use of chi(2) analysis. For some categories of therapy and DME, physicians and residents reported that they would take an active role in prescription decisions, and their reliance on specialty consultation increased appropriately with the increasing complexity of the device or therapy. However, respondents generally seemed to share responsibility rather than rely on themselves as sole decision makers for most categories; fewer than one fourth took sole responsibility. Reliance on nonphysician health care providers was evident for all categories; in some cases, up to half of the respondents would allow therapists to take over these decisions, and a small but significant percentage of physicians would entrust DME prescription decisions to vendors alone. Our findings indicate that many practicing pediatricians and those in training may be unwilling to assume sole responsibility in prescribing and managing therapies and DME for CWSN. Although the number who would rely on consultation with specialists is somewhat reassuring, we found that a significant percentage would turn to nonphysician health care providers and even vendors to make these decisions in some cases, raising liability implications, conflict-of-interest issues, and quality-of-care issues. To protect themselves and their patients from fraud and inappropriate prescriptions and medical management, pediatricians must become increasingly conscientious about complying with American Medical Association guidelines and federal and state laws regarding initiation and supervision of therapies and DME. We offer some recommendations that may help to address this problem.


Generation of marker-free plastid transformants using a transiently cointegrated selection gene.
Genetic engineering of higher plant plastids typically involves stable introduction of antibiotic resistance genes as selection markers. Even though chloroplast genes are maternally inherited in most crops, the possibility of marker transfer to wild relatives or microorganisms cannot be completely excluded. Furthermore, marker expression can be a substantial metabolic drain. Therefore, efficient methods for complete marker removal from plastid transformants are necessary. One method to remove the selection gene from higher plant plastids is based on loop-out recombination, a process difficult to control because selection of homoplastomic transformants is unpredictable. Another method uses the CRE/lox system, but requires additional retransformation and sexual crossing for introduction and subsequent removal of the CRE recombinase. Here we describe the generation of marker-free chloroplast transformants in tobacco using the reconstitution of wild-type pigmentation in combination with plastid transformation vectors, which prevent stable integration of the kanamycin selection marker. One benefit of a procedure using mutants is that marker-free plastid transformants can be produced directly in the first generation (T0) without retransformation or crossing.


Perceived control moderates the impact of academic stress on the attention process of working memory in male college students.
Academic stress is a common long-term stress among the student population and is known to impact working memory within the frontoparietal attention network. Perceived control is an individual variation that may play a buffering role between stress and overall adjustment. In this study, we addressed the moderating effects of perceived control between academic stress and working memory. Fifty-nine male college students participated in the study. Academic stress and perceived control were assessed before participants completed a working memory (n-back) task. Event-related potentials (ERPs) including P2 and P3 were analyzed to examine the attention and maintenance processes of working memory. A moderating effect of perceived control on the relationship between academic stress and working memory was found. For students with low levels of perceived control, academic stress was negatively associated with P2 amplitudes at the high workload (3-back) task, suggesting a negative impact on attention process of working memory. In contrast, academic stress did not affect students with high and moderate levels of perceived control. The results indicate that perceived control may serve as a buffer to protect the cognitive function from the disruption of academic stress.


Treatment of unprotected left main coronary artery stenosis in the drug-eluting stent era.
Coronary angiography is often inadequate for estimating the severity of ambiguous left main coronary artery (LMCA) stenoses. Our assessment of these lesions can be improved by the techniques of intravascular ultrasound and fractional flow reserve which provide indices of stenosis severity to enable the prediction of future events and planning of treatment. For patients requiring LMCA revascularization, coronary artery bypass graft (CABG) surgery has been gold standard for decades. However, this technique continues to be limited by factors such as periprocedural mortality, prolonged hospital stay and rehabilitation, and long-term graft patency. LMCA stenosis remains one of the few serious challenges for the interventional cardiologists and, in the bare metal stent era, the long-term results were not sufficient to replace CABG surgery, mainly because of the high restenosis rate. Drug-eluting stents (DES) have dramatically reduced the restenosis rate and early results in small series (approximately 300 patients in total) treated with DES in LMCA have been encouraging, especially for lesions at the ostium and in the left main shaft. Before changes are made in the guidelines for treatment, we must wait for a refinement in the technique and stent design used for bifurcational left main lesion and the results of randomized, specific multicenter studies (SYNTAX trial). It is likely that, for selected patients, LMCA stenosis will be regarded as an indication for PCI.


Oxidized Lipids: Common Immunogenic Drivers of Non-Alcoholic Fatty Liver Disease and Atherosclerosis.
The prevalence of non-alcoholic fatty liver disease (NAFLD), ranging from simple steatosis to inflammatory steatohepatitis (NASH) and cirrhosis, continues to rise, making it one of the major chronic liver diseases and indications for liver transplantation worldwide. The pathological processes underlying NAFLD not only affect the liver but are also likely to have systemic effects. In fact, growing evidence indicates that patients with NAFLD are at increased risk for developing atherosclerosis. Indeed, cardiovascular complications are the leading cause of mortality in NAFLD patients. Here, we aim to address common pathophysiological molecular pathways involved in chronic fatty liver disease and atherosclerosis. In particular, we focus on the role of oxidized lipids and the formation of oxidation-specific epitopes, which are important targets of host immunity. Acting as metabolic danger signals, they drive pro-inflammatory processes and thus contribute to disease progression. Finally, we summarize encouraging studies indicating that oxidized lipids are promising immunological targets to improve intervention strategies for NAFLD and potentially limit the risk of developing atherosclerosis.


Between less eligibility and the NHS: the changing place of poor law hospitals in England and Wales, 1929-39.
In 1929, the Local Government Act broke up the apparatus of the Poor Law Guardians and Unions, and transferred responsibility for the care of the poor to local councils. In theory, the period between the passing of the Act and the formation of the National Health Service witnessed a large-scale reclassification of the sick poor as patients rather than paupers. In reality, as this investigation of contemporary judgements of hospital quality and bed and staff numbers in English and Welsh county boroughs shows, the national picture was very varied at the local level. Local and sometimes regional traditions of care, finance and council priorities had a large influence on the ongoing development of a unified medical service which included the poor. In the best case scenario, hospitals were classified by patient type, and the principle of 'less eligibility' was discarded. Elsewhere, economic status continued to direct medical treatment, but in almost all cases, the chronic and elderly poor were more likely to remain in low-quality and unmodernized buildings than the acutely sick. The investigation highlights the disjuncture between the changed vision for the sick poor and its patchy enforcement on the ground.


Ribonucleotide reductase--structural studies of a radical enzyme.
Ribonucleotide reductase contains a stable organic free radical essential for its activity located on a tyrosine residue in the small subunit of the enzyme called R2. The substrate binding site is, however, found in the catalytic subunit called R1. A long-range protein-mediated radical transfer pathway appears to be responsible for the delivery of the radical from the tyrosine in R2 to the substrate on R1. The active site is located deep inside the protein in a very stable beta/alpha-barrel structure and a hydrogen bonded system leads from the surface to Cys439 at the active site which is in excellent position to remove a hydrogen from the 3' of the ribose of a bound substrate nucleotide.


Developments in aquatic insect biomonitoring: a comparative analysis of recent approaches.
Aquatic insects and other benthic invertebrates are the most widely used organisms in freshwater biomonitoring of human impact. Because of the high monetary investment in freshwater management, decisions are often based on biomonitoring results, and a critical and comparative review of different approaches is required. We used 12 criteria that should be fulfilled by an "ideal" biomonitoring tool, addressing the rationale, implementation, and performance of a method. After illustrating how the century-old but still widely used Saprobian system does not meet these criteria, we apply them to nine recent approaches that range from the suborganismal to the ecosystem level. Although significant progress has been made in the field, no recent approach meets all 12 criteria. Given that the use of biomonitoring information has important financial consequences, we suggest that societies and governments prioritize how these criteria should be ranked.


Neuroimaging in vascular cognitive impairment: a state-of-the-art review.
Imaging is critical in the diagnosis and treatment of dementia, particularly in vascular cognitive impairment, due to the visualization of ischemic and hemorrhagic injury of gray and white matter. Magnetic resonance imaging (MRI) and positron emission tomography (PET) provide structural and functional information. Clinical MRI is both generally available and versatile - T2-weighted images show infarcts, FLAIR shows white matter changes and lacunar infarcts, and susceptibility-weighted images reveal microbleeds. Diffusion MRI adds another dimension by showing graded damage to white matter, making it more sensitive to white matter injury than FLAIR. Regions of neuroinflammatory disruption of the blood-brain barrier with increased permeability can be quantified and visualized with dynamic contrast-enhanced MRI. PET shows metabolism of glucose and accumulation of amyloid and tau, which is useful in showing abnormal metabolism in Alzheimer's disease. Combining MRI and PET allows identification of patients with mixed dementia, with MRI showing white matter injury and PET demonstrating regional impairment of glucose metabolism and deposition of amyloid. Excellent anatomical detail can be observed with 7.0-Tesla MRI. Imaging is the optimal method to follow the effect of treatments since changes in MRI scans are seen prior to those in cognition. This review describes the role of various imaging modalities in the diagnosis and treatment of vascular cognitive impairment.


Pyrophosphorylases in Solanum tuberosum: I. Changes in ADP-Glucose and UDP-Glucose Pyrophosphorylase Activities Associated with Starch Biosynthesis during Tuberization, Maturation, and Storage of Potatoes.
Changes in ADP-glucose and UDP-glucose pyrophosphorylase activities were followed during tuber development of Solanum tuberosum and prolonged storage at 4 and 11 C. Potato tuberization was accompanied by a sharp increase in starch synthesis simultaneous with a marked rise in ADP-glucose pyrophosphorylase activity. When tubers reached an average diameter of 1 centimeter (0.5 gram average tuber weight) and had already established 58% starch on a dry weight basis, ADP-glucose pyrophosphorylase increased 16- to 24-fold over its activity seen in low starch containing stolon tissue. During this same period UDP-glucose pyrophosphorylase increased approximately 2- to 3-fold. Although participation of UDP-glucose in starch formation can not be neglected, it is suggested that the onset of rapid non-photosynthetic potato tuber starch biosynthesis may be closely related to the simultaneous increase in ADP-glucose pyrophosphorylase activity.Evidence that UDP-glucose and ADP-glucose pyrophosphorylases are separate protein entities was indicated by their (a) activity ratio variations during tuber development and storage, (b) extraction stabilities, (c) morphological localization, (d) separation with ammonium sulfate, (e) pH optima, and (f) differential activation with 3-P-glycerate.


Granular polymer solution.
We have measured the spectrum of fluctuations in the size of a granular polymer in a granular solvent. The system consists of a linear chain of plastic spheres immersed in a planar fluid of self-propelled balls. The time average of the end-to-end length r of the chain scales with the number of links N according to <r(2)> approximately N2nu, with nu=0.75+/-0.01. This provides an experimental test of the theoretical value nu=3 / 4 of the critical exponent for a self-avoiding random walk in two dimensions. The measured probability distribution P(r) is compared with the universal function of the scaling theory.


Developing a health promotion program for faith-based communities.
The article describes the partnership formed between community outreach programs, a school of nursing, and hospitals to implement Healthy People 2010 goals in urban, faith-based communities. To date this program has provided health promotion programs to 125 people from more than 18 congregations in the context of their faith setting. The program has allowed congregants to develop ministry strategies to meet health care needs within the congregation and community. The article provides overall program goals, specific lesson plans, and evaluation strategies. Outcome measures include an increase in health promotion knowledge, participant satisfaction, and improved health in congregations.


Burnout among German oncologists: a cross-sectional study in cooperation with the Arbeitsgemeinschaft Internistische Onkologie Quality of Life Working Group.
Oncologists are at an increased risk of developing burnout, leading to negative consequences in patient care and in professional satisfaction and quality of life. This study was designed to investigate exhaustion and disengagement among German oncologists and assess the prevalence of burnout among oncologists within different professional settings. Furthermore, we wanted to examine possible relations between sociodemographic factors, the oncological setting, professional experience and different aspects of burnout. In a cross-sectional study design, an Internet-based survey was conducted with 121 oncologists between April and July 2020 using the Oldenburg Burnout Inventory, which contains items on exhaustion, disengagement, and burnout. Furthermore, sociodemographic data of the participants were assessed. The participants were members of the Working Group Medical Oncology (Arbeitsgemeinschaft Internistische Onkologie) within the German Cancer Society. The survey showed a burnout prevalence of 43.8%, which correlated with age and professional experience; that is, the prevalence is particularly high among younger oncologists. Exhaustion is closely related to employment status; that is, it was significantly higher among employed oncologists. There were remarkably low levels of disengagement among oncologists, highlighting the own demand to fulfil job requirements despite imminent or actual overburdening in daily work. More support is necessary to mitigate the professional stressors in the healthcare system. To ensure quality medical care, employees should be offered preventive mental health services early in their careers.


Auditory-nerve responses predict pitch attributes related to musical consonance-dissonance for normal and impaired hearing.
Human listeners prefer consonant over dissonant musical intervals and the perceived contrast between these classes is reduced with cochlear hearing loss. Population-level activity of normal and impaired model auditory-nerve (AN) fibers was examined to determine (1) if peripheral auditory neurons exhibit correlates of consonance and dissonance and (2) if the reduced perceptual difference between these qualities observed for hearing-impaired listeners can be explained by impaired AN responses. In addition, acoustical correlates of consonance-dissonance were also explored including periodicity and roughness. Among the chromatic pitch combinations of music, consonant intervals/chords yielded more robust neural pitch-salience magnitudes (determined by harmonicity/periodicity) than dissonant intervals/chords. In addition, AN pitch-salience magnitudes correctly predicted the ordering of hierarchical pitch and chordal sonorities described by Western music theory. Cochlear hearing impairment compressed pitch salience estimates between consonant and dissonant pitch relationships. The reduction in contrast of neural responses following cochlear hearing loss may explain the inability of hearing-impaired listeners to distinguish musical qualia as clearly as normal-hearing individuals. Of the neural and acoustic correlates explored, AN pitch salience was the best predictor of behavioral data. Results ultimately show that basic pitch relationships governing music are already present in initial stages of neural processing at the AN level.


[he use ethylmethylhydroxypyridine succinate in the treatment of patients with heart failure].
We studied impact of ethylmethylhydroxypyridine succinate n the course of chronic heart failure during 3 years follow-up after myocardial infarction. Dynamics of objective and subjective parameters was assessed in 100 patients; 48 patients received conventional therapy (control group) and 52 patients received conventional therapy plus ethylmethylhydroxypyridine succinate (main group). Addition of ethylmethylhydroxypyridine succinate resulted in decreases of rates of complications, mortality, and re-hospitalizations. Increases of myocardial contractile function, myocardial adaptation, as well as improvement of range of biochemical parameters were also observed. The latter changes were indicative of antioxidant, anti-inflammatory, anti-stress activities of Ethylmethylhydroxypyridine succinate. Moreover, antidepressant and antineurotic effects of complex therapy including ethylmethylhydroxypyridine succinate was confirmed.


Predictive value of Medicare claims data for identifying revision of index hip replacement was modest.
To determine the positive predictive value of Medicare claims for identifying revision of total hip replacement (THR), a frequent marker of THR quality and outcome. We obtained Medicare Part A (Hospital) claims from seven states on patients that had primary THR from July 1995 through June 1996. We searched claims to determine whether these THR recipients had a subsequent revision THR through December 2006. We selected a sample of subjects with codes indicating both index primary and subsequent revision THR. We obtained medical records for both procedures to establish whether the revision occurred on the same side as index primary THR. Three hundred seventy-four subjects had codes indicating primary THR in 1995-96 and subsequent revision. Seventy-one percent (95% confidence interval: 66, 76) of the revisions were performed on the index joint and would be correctly attributed as revisions of the index THR, using Medicare claims data. Claims data on revision THR that do not contain information on the side that was operated on are ambiguous with respect to whether the revision was performed on the index or contralateral side. Claims-based analyses of revisions after an index THR should acknowledge and adjust for this source of potential misclassification.


Effect of Patient Positioning on Measurement of the Anterior Center-Edge Angle on False-Profile Radiographs and Its 3-Dimensional Mapping to the Acetabular Rim.
The anterior center-edge angle (ACEA) is used to quantify anterior coverage of the femoral head by the acetabulum. However, its measurement has not been evaluated in a manner consistent with routine use, and the precise 3-dimensional (3D) anatomic location where it measures coverage is not known. To determine the effect of patient positioning on ACEA measurement reliability, magnitude, and 3D location. Descriptive laboratory study. Included were 18 adults; 7 participants had cam morphology and femoroacetabular impingement syndrome, and 11 participants had no radiographic evidence of hip abnormalities and no history of hip pain or injuries. Ultimately, 3D femur and pelvis models were generated from computed tomography images. Radiographs were generated with the models in different degrees of pelvic rotation, tilt, and obliquity relative to the standard false-profile view. The ACEA was measured by 2 raters by selecting the location of the bone edge on each radiograph. Selections were projected onto the pelvis model and expressed as a clockface location on the acetabular rim. The clockface was mirrored on left hips to allow a direct comparison of locations between hips. Interrater and intrarater reliability were quantified via the intraclass correlation coefficient (ICC). The effect of position on ACEA measurements and clockface locations was determined via linear regression. Intrarater and interrater reliability were excellent (ICC ≥0.97 for all). For every degree increase in rotation, tilt, and obliquity, the ACEA changed by +0.53°, +0.93°, and -0.04°, respectively. The mean clockface location (hour:minute:second) in the false-profile view was 2:09:32 ± 0:12:00 and changed by +0:02:08, -0:00:35, and -0:00:05 for every degree increase in rotation, tilt, and obliquity, respectively. ACEA measurements were reliable even with differences in patient positioning. Rotation and tilt were associated with notable changes in ACEA measurements. ACEA bone edge measurements mapped to the anterosuperior acetabular rim, typically in proximity to the anterior inferior iliac spine. Mapped location was most sensitive to rotation. Pelvic rotation and tilt affected ACEA measurements, which could alter the clinical classification and treatment of borderline abnormalities. Rotation in particular must be well controlled during patient imaging to preserve measurement reliability and accuracy and to describe coverage from the intended 3D rim location.


PLGA+Fe₃O₄+PFP Nanoparticles Drug-Delivery Demonstrates Potential Anti-Tumor Effects on Tumor Cells.
BACKGROUND Nanoparticles are proven as a potential tool for treating various disorders. However, efficient nanoparticle delivery of anti-tumor drugs is urgently needed for tumor treatment. This study aimed to generate a drug-delivery nanoparticle with higher efficacy and safety. MATERIAL AND METHODS We developed a poly-(lactide-co-glycolide) (PLGA) nanoparticle (FLGA-Fe₃O₄+PFP) embedded with super-paramagnetic iron oxide (Fe₃O₄) and perfluoropentane (PFP). Characteristics of FLGA-Fe₃O₄+PFP nanoparticles were observed using optical microscopy, scanning electron microscopy, and transmission electron microscopy. HNE1 and HepG2 cells were cultured and used for experiments. MTT was used to evaluate cytotoxic effects of FLGA-Fe₃O₄+PFP nanoparticles on HNE1 and HepG2 cells. Cell engulfment capacity was examined and a cell targeting experiment was conducted to evaluate invasive capability and binding efficiency of PLGA+Fe₃O₄+PFP nanoparticles, respectively. Biological toxicity of PLGA+Fe₃O₄+PFP nanoparticles in rats was evaluated by determining CK, LDH, creatinine, and UA levels, and ALT and AST activities. RESULTS PLGA+Fe₃O₄+PFP nanoparticles demonstrated well-defined spherical and dispersed morphology with smooth surfaces. There were scattered black spots on shells of PLGA+Fe₃O₄+PFP nanoparticles. PLGA+Fe₃O₄+PFP nanoparticles did not trigger obvious effects on cell viability of HNE1 and HepG2 cells. HNE1 and HepG2 cells demonstrated higher engulfment capacity for PLGA+ Fe₃O₄+PFP nanoparticles. PLGA+Fe₃O₄+PFP nanoparticles demonstrated higher targeting CDDP delivery efficacy and promoted binding efficiency of targeting CDDP with cells. PLGA+Fe₃O₄+PFP nanoparticles demonstrated no obvious toxic effects on heart, kidney, liver (without effects on CK, LDH, creatinine, UA levels, and ALT and AST activities). CONCLUSIONS PLGA+Fe₃O₄+PFP nanoparticles were safe, with higher invasive ability and binding efficiency of targeting CDDP with tumor cells. Therefore, PLGA+Fe₃O₄+PFP nanoparticles demonstrated potential anti-tumor effects after transplantation.


[Adipose tissue stromal cells -- multipotent cells with therapeutic potential for stimulation of angiogenesis in tissue ischemia].
Results of studies of properties of adipose tissue stromal cells are summarized in this review. It contains data on separation and cultivation of these cells as well as description of their antigenic characteristics, ability to differentiate into cells of mesenchymal and nonmesenchymal origin, angiogenic potential, and potential for transfection and transfer of therapeutic genes. Analysis of perspectives of clinical use of adipose tissue stromal cells in therapy of cardiovascular and other diseases is also presented.


Genetic alterations shaping tumor response to anti-EGFR therapies.
The Epidermal Growth Factor Receptor (EGFR) has been targeted through the development of selective tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAb). These molecules have shown effectiveness in a subset of patients with specific genetic alterations (i.e. gain-of-function EGFR mutations or EGFR gene amplification) and have been approved for their use in non-small-cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic cancer and head and neck cancer. In addition, extensive research is being performed in many other tumour types hoping for a future approval. However, the majority of the patients show no benefit from these molecules due to primary mechanisms of resistance, already present before treatment or show disease progression upon the acquisition of drug resistance mechanisms during the treatment. At present, the majority of patients display resistance due to alterations in genes related to the EGFR signalling pathway that eventually circumvent EGFR inhibition and allow cancer progression. Thus, in this review article we focus on the molecular mechanisms underlying drug resistance via genetic alterations leading to resistance to all anti-EGFR drugs approved by the FDA and/or EMA. We also discuss novel approaches to surmount these chemoresistance modalities.


The origin of red algae and cryptomonad nucleomorphs: A comparative phylogeny based on small and large subunit rRNA sequences of Palmaria palmata, Gracilaria verrucosa, and the Guillardia theta nucleomorph.
The complete large subunit rRNA sequences from the red algae Palmaria palmata and Gracilaria verrucosa, and from the nucleomorph of the cryptomonad Guillardia theta, were determined in order to assess their phylogenetic relationships relative to each other and to other eukaryotes. Neighbor-joining, maximum-parsimony, and maximum-likelihood trees were constructed on the basis of small subunit rRNA, large subunit rRNA, and a combination of both molecules. Our results support the hypothesis that the cryptomonad plastid is derived from a primitive red alga, in that an ancient common ancestor of rhodophytes and cryptomonad nucleomorphs is indicated. This cluster shows some affinity with chlorobionts, which could point to a monophyletic origin of green and red plastids. However, the exact branching order of the crown eukaryotes remains uncertain and further research is required.


Corticosteroid-induced apoptosis of airway epithelium: a potential mechanism for chronic airway epithelial damage in asthma.
Damage to the airway epithelium is one prominent feature of chronic asthma. Mucosal damage includes gap openings, partial denudation, and loss of ciliated cells. Apoptosis of the airway epithelium is increasingly recognized as a potential mechanism by which damage may occur. Corticosteroids (CSs) induce apoptosis in inflammatory cells, which in part explains their ability to suppress airway inflammation. However, CS therapy does not necessarily reverse epithelial damage. We examined whether CS therapy actually could induce airway epithelial apoptosis using culture models of primary airway epithelial cells and cell lines. The administration of CSs in low-micromolar concentrations induces apoptosis that involves the disruption of mitochondrial polarity, the activation of caspases, and the involvement of Bcl-2. Clear differences exist between CS-induced apoptosis in the cultured epithelium vs cultured hematopoietic cells in regard to time course and resistance to apoptosis. Our data suggest that the use of CSs, in concentrations that could be attained in vivo with the inhalation of potent preparations or with systemic administration, may be one factor in the airways remodeling and epithelial damage that is seen in many patients with chronic, persistent asthma.


Combating meaninglessness: on the automatic defense of meaning.
Research has found that a substantial portion of human cognition occurs beyond conscious awareness to satisfy the superordinate goal of maintaining meaning. Three experiments used a newly developed method to examine the features of meaning and how individuals automatically defend against threats to meaning. In Experiment 1, individuals who subliminally processed meaninglessness-related words, relative to those in a control group, reported being more religious and having more meaningful lives. Experiment 2 extended these results, as individuals whose meaning was threatened bolstered alternative domains of meaning (termed fluid compensation) by reporting higher self-esteem, need for closure, symbolic immortality, and a reduced need to belong. Experiment 3 ruled out an alternative explanation and clarified the effects of threatened meaning on one's need to belong. These findings elucidate the processes of meaning maintenance in sustaining psychological equanimity. Implications for the automatic defense of meaning are discussed.


Importance of dressing removal before radiolabeled WBC imaging for musculoskeletal infection.
Leukocyte imaging performed with in-111 or Tc-99m is gaining widespread acceptance as a method for detection of osteomyelitis associated with soft tissue injury or infection. The authors present three cases in which initial imaging was suggestive of a focal infectious process in bone and soft tissue. However, repeat imaging after the removal of wound dressings, which revealed sero-sanguineous discharge in all cases, resulted in a scan appearance that was much less remarkable for focal radiotracer accumulation in the bone. The authors conclude that accumulation of labeled WBCs in wound discharge can result in scans that are false-positive for osteomyelitis. Therefore, the authors recommend that wounds should be cleaned and dressings changed before imaging in order to avoid scans that are false-positive for osteomyelitis.


On the origin of extracellular glutamate levels monitored in the basal ganglia of the rat by in vivo microdialysis.
Several putative neurotransmitters and metabolites were monitored simultaneously in the extracellular space of neostriatum, substantia nigra, and cortex and in subcutaneous tissue of the rat by in vivo microdialysis. Glutamate (Glu) and aspartate (Asp) were at submicromolar and gamma-aminobutyric acid (GABA) was at nanomolar concentrations in all brain regions. The highest concentration of dopamine (DA) was in the neostriatum. Dynorphin B (Dyn B) was in the picomolar range in all brain regions. Although no GABA, DA, or Dyn B could be detected in subcutaneous tissue, Glu and Asp levels were 5 and approximately 5 and approximately 0.4 microM, respectively. Lactate and pyruvate concentrations were approximately 200 and approximately 10 microM in all regions. The following criteria were applied to ascertain the neuronal origin of substances quantified by microdialysis: sensitivity to (a) K+ depolarization, (b) Na+ channel blockade, (c) removal of extracellular Ca2+, and (d) depletion of presynaptic vesicles by local administration of alpha-latrotoxin. DA, Dyn B, and GABA largely satisfied all these criteria. In contrast, Glu and Asp levels were not greatly affected by K+ depolarization and were increased by perfusing with tetrodotoxin or with Ca2+-free medium, arguing against a neuronal origin. However, Glu and Asp, as well as DA and GABA, levels were decreased under both basal and K+-depolarizing conditions by alpha-latrotoxin. Because the effect of K+ depolarization on Glu and Asp could be masked by reuptake into nerve terminals and glial cells, the reuptake blocker dihydrokainic acid (DHKA) or L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) was included in the microdialysis perfusion medium. The effect of K+ depolarization on Glu and Asp levels was increased by DHKA, but GABA levels were also affected. In contrast, PDC increased only Glu levels. It is concluded that there is pool of releasable Glu and Asp in the rat brain. However, extracellular levels of amino acids monitored by in vivo microdialysis reflect the balance between neuronal release and reuptake into surrounding nerve terminals and glial elements.


WIMP dark matter candidates and searches-current status and future prospects.
We review several current aspects of dark matter theory and experiment. We overview the present experimental status, which includes current bounds and recent claims and hints of a possible signal in a wide range of experiments: direct detection in underground laboratories, gamma-ray, cosmic ray, x-ray, neutrino telescopes, and the LHC. We briefly review several possible particle candidates for a weakly interactive massive particle (WIMP) and dark matter that have recently been considered in the literature. We pay particular attention to the lightest neutralino of supersymmetry as it remains the best motivated candidate for dark matter and also shows excellent detection prospects. Finally we briefly review some alternative scenarios that can considerably alter properties and prospects for the detection of dark matter obtained within the standard thermal WIMP paradigm.


[Autocrine stimulation of receptor-tyrosine kinases (RTK) in human tumor cell lines in vitro: therapeutic implications].
The VEGF/VEGFR system is known to play an important role in the development of new blood vessels during tumor formation. There is evidence that VEGFRs are not only present on endothelial cells but also on tumor cells. Since VEGF is able to induce proliferation and migration via VEGFR-2 we have studied the expression of VEGFRs and related receptor tyrosine kinases (RTKs) in different tumor cell lines and the effect of growth factor stimulation. RTK expression was investigated in 5 different human tumor cell lines on protein and mRNA levels. Tumor cell lines were exposed to growth factors such as VEGF and the phosphorylation of downstream molecules involved in proliferation, migration and apoptosis were assessed. Under comparable conditions proliferation and migration essays were performed. Endogenous production of VEGF and PDGF by the tumor cells was measured by ELISA of cell culture supernatants. Most tested cell lines expressed all known VEGFR's, PDGFR-beta on protein and mRNA levels to a varying extent. 3 out of 5 cell lines could be stimulated after addition of VEGF reflected by an increased phosphorylation of MAPK, AKT/PKB and to a lesser extent of p38. This was underlined by an increased cell number and reduced number of apoptotic cells. After stimulation with PDGF-BB a stronger induction of MAPK and AKT/PKB phosphorylation than for VEGF could be seen. In contrast, no effect on tumor cell migration was detectable in all examined cell lines. The investigation of cell culture supernatants revealed that most cell lines do not produce VEGF or PDGF. Tumor cell lines express RTKs and the receptor is stimulable after addition of growth factors such as VEGF. Thus, secretion of groth factors in the tumor microenvironment is not only able to stimulate proliferation and survival of endothelial cells but also tumor cells themselve. One cell line displayed high levels of endogenous VEGF which could explain the lack of an increased cell number after addition of VEGF. It remains obscure why another cell line could not be stimulated although receptors were present at the cellular surface. Further investigations should prove that RTK's could be influenced by therapeutic drugs in order to suppress cell proliferation and migration and induce apoptosis in tumor cell lines.


Pluronic-Coated Biogenic Gold Nanoparticles for Colon Delivery of 5-Fluorouracil: In vitro and Ex vivo Studies.
The aim of the study was to prepare 5-fluorouracil (5-FU)-loaded biogenic gold nanoparticles with pluronic-based coating (PFGNPs), their optimization (full factorial predicted OBPN-1) and in vitro-ex vivo evaluation. Several formulations were prepared, selected for optimization using Design Expert®, and compared for morphology, 5-FU release kinetics, compatibility, cell line toxicity, in vitro hemocompatibility, and ex vivo intestinal permeation across the rat duodenum, jejunum, and ileum. The pluronic-coated 5-FU-carrying GNPs were spherical, 29.11-178.21 nm in diameter, with a polydispersity index (PDI) range of 0.191-292, and a zeta potential (ZP) range of 11.19-29.21 (-mV). The optimized OBPN-1 (desirability = 0.95) demonstrated optimum size (175.1 nm), %DL as 73.8%, ZP as 21.7 mV, % drug release (DR) as 75.7%, and greater cytotoxicity (viability ~ 8.9%) against the colon cancer cell lines than 5-FU solution (~ 24.91%), and less hemocompatibility. Moreover, OBPN-1 exhibited 4.5-fold permeation across the rat jejunum compared with 5-FU solution. Thus, the PFGNPs exhibit high DL capacity, sustained delivery, hemocompatibility, improved efficacy, and enhanced permeation profiles compared with 5-FU solution and several other NPs preparations suggesting it is a promising formulation for effective colon cancer control with reduced side effects.


Clinical and molecular pathological features of severe childhood autosomal recessive muscular dystrophy in Saudi Arabia.
The clinical, biochemical and histochemical features of 14 patients (nine females and five males) with severe childhood autosomal recessive muscular dystrophy (SCARMD) seen at a tertiary hospital in Riyadh from 1982 to 1993 are described. Onset was at 3 to 9 (median 3) years and four of five children aged > 12 years lost ambulation. Five of the eight pairs of parents were closely consanguineous. The mean creatine kinase was 20 times the upper normal limit. Histochemistry of muscle showed dystrophic features in all cases, and dystrophin was positive in all cases examined (N = 6). Three patients (two girls and a boy) were deficient in adhalin, the 50-kDa dystorphin-associated glycoprotein. A boy aged 13 years had rapidly progressing disease. Another boy of the same age (from a family characterized by early onset and slower progression) had normal dystrophin and adhalin. The clinical features conformed with previous observations from Sudan, North Africa and Qatar in the Arabian Peninsula. The disease is common in Saudi Arabia and seems to be more prevalent than Duchenne muscular dystrophy.


Goitrous congenital hypothyroidism and hearing impairment associated with mutations in the TPO and SLC26A4/PDS genes.
Pendred syndrome (PS) and thyroid peroxidase (TPO) deficiency are autosomal-recessive disorders that result in thyroid dyshormonogenesis. They share congenital hypothyroidism, goiter, and an iodide organification defect as common features. Whereas the hallmark of PS is sensorineural deafness, other forms of congenital hypothyroidism may also lead to hearing impairment. Therefore, a definite diagnosis may be difficult and require molecular genetic analyses. The propositus presented at birth with primary hypothyroidism and goiter. He also had congenital bilateral moderate hearing loss, and PS was suspected. We sequenced the SLC26A4/PDS and TPO genes in the propositus and tested familial segregation of mutations in all available family members who were phenotypically normal. The functional consequences of the identified pendrin mutation (p.R776C) were studied in vitro. Sequencing of the SLC26A4/PDS gene revealed a single monoallelic missense mutation in the propositus (p.R776C). This mutation, which was inherited from his unaffected mother, has previously been identified in an individual with deafness and an enlarged vestibular aqueduct. Sequencing of the TPO gene revealed compound heterozygosity for a novel nonsense mutation (p.Q235X) and a known missense mutation (p.Y453D). The mutant pendrin (p.R776C) retained its ability to transport iodide in vitro. These results show that the propositus carries three sequence variants in two genes: a monoallelic SLC26A4/PDS sequence variant and compound heterozygous TPO mutations. Our study illustrates that if only a single heterozygous SLC26A4/PDS mutation is found in a patient with goiter and deafness, other genetic explanations should be considered.


Effectively Adapting and Implementing In-Person Teacher Professional Development to a Virtual Format.
A year of COVID-19 quarantine required educators to switch from in-person to virtual learning platforms, causing a dramatic reimagining of their daily praxis. Their experiences are likely to influence new norms for K-12 education. While virtual learning can be effective, student engagement, student retention, and student attention can be challenging. This paper discusses how we adapted a materials-heavy, hands-on, annual summer teacher professional development (PD) program from an in-person to a virtual platform in the initial months of the pandemic. We successfully maintained effective and hands-on components, giving authentic learning experiences to the participants. The 2020 virtual version of the program effectively engaged in-service teachers with high daily participation and retention rates. Nearly all participants rated the workshops as very good or excellent, and an assessment of participants' learning outcomes was comparable to that of the highly-rated in-person 2018 version of the program. Following the PD session, teachers reported feeling more prepared to facilitate their students' learning, increased inquiry-based science teaching knowledge and skills, and their enthusiasm for utilizing workshop strategies. While there are challenges to implementing virtual learning, virtual teacher PD can be widely adaptable and replicable for many institutions, especially in situations in which distance or finances deter in-person participation.


Blood DNA methylation markers in potentially identified Chinese patients with hepatocellular carcinoma.
To determine whether blood DNA methylation is associated with hepatocellular carcinoma (HCC) for Chinese patients, we used genome-wide DNA methylation detection to access the blood samples of Chinese patients by Illumina Human methylation 450K arrays. Sixty potentially gene locis which had different methylated levels significantly among tumor and adjacent normal tissues would be tested in this study. A previous study was conducted in China communities and followed with 7 years. The DNA from white blood cells (WBC) from 192 patients with HCC and 215 matched controls were assayed in this study. The χ2 test was used to measure data to categorize variables and t -test was used to evaluate the different characteristics among groups. Besides, odds ratios (OR) and 95%CI was calculated for matching factors by conditional logistic regression models. We found that high methylation in WNK2 was related to increased risk of HCC, and high methylation in TPO were related to decreased risk of HCC. In our multivariable conditional logistic regression models, these results all exist. Those findings support the methylated changes of WNK2 and TPO may become a new detection index for HCC patients in clinical laboratory. However, the results should be replicated in additional prospective studies with lager samples.


Molecular Mechanisms of Chronic Wasting Disease Prion Propagation.
Prion disease epidemics, which have been unpredictable recurrences, are of significant concern for animal and human health. Examples include kuru, once the leading cause of death among the Fore people in Papua New Guinea and caused by mortuary feasting; bovine spongiform encephalopathy (BSE) and its subsequent transmission to humans in the form of variant Creutzfeldt-Jakob disease (vCJD), and repeated examples of large-scale prion disease epidemics in animals caused by contaminated vaccines. The etiology of chronic wasting disease (CWD), a relatively new and burgeoning prion epidemic in deer, elk, and moose (members of the cervid family), is more enigmatic. The disease was first described in captive and later in wild mule deer and subsequently in free-ranging as well as captive Rocky Mountain elk, white-tailed deer, and most recently moose. It is therefore the only recognized prion disorder of both wild and captive animals. In addition to its expanding range of hosts, CWD continues to spread to new geographical areas, including recent cases in Norway. The unparalleled efficiency of the contagious transmission of the disease combined with high densities of deer in certain areas of North America complicates strategies for controlling CWD and raises concerns about its potential spread to new species. Because there is a high prevalence of CWD in deer and elk, which are commonly hunted and consumed by humans, the possibility of zoonotic transmission is particularly concerning. Here, we review the current status of naturally occurring CWD and describe advances in our understanding of its molecular pathogenesis, as shown by studies of CWD prions in novel in vivo and in vitro systems.


Psychological factors after traumatic amputation in landmine survivors: the bridge between physical healing and full recovery.
Limb loss due to a landmine injury is sudden and devastating. The resulting disability makes life challenging in a world where physical ability is the 'norm'. In order to better understand the psychological adjustments individuals make in their recovery from a landmine injury, the Landmine Survivors Network conducted an exploratory qualitative study to determine factors that contribute to an individual's recovery. The study examined psychosocial aspects, coping strategies, and resilience characteristics of limb loss survivors across differing cultural, societal and economic backgrounds. Eighty-five participants (68 persons of limb loss, 10 family members, seven service providers) were interviewed using a semi-structured protocol in the USA and an open-ended format in six landmine affected countries. Data analysis was completed using grounded theory analytic strategies. Data indicated that the survivors' acceptance of limb loss and their state of psychological recovery were greatly influenced by the individual's resilience characteristics, social support, medical care, economic situation and societal attitudes toward people with disabilities. Recovery from traumatic amputation in landmine survivors needs to be comprehensive and coordinated, and requires addressing the individual's physical, psychological, economic and social needs within the context of family, community, and the socio-cultural environment in which they live.


Sulfiredoxin involved in the protection of peroxiredoxins against hyperoxidation in the early hyperglycaemia.
As a direct consequence of hyperglycaemia, the excessive generation of ROS is central to the pathogenesis of diabetic cardiomyopathy. We hypothesize that stimulation of high glucose (HG) results in an increased sulfiredoxin (Srx) expression, which regulates ROS signaling through reducing the hyperoxidized peroxiredoxins (Prxs). We show that hyperoxidized Prxs were initially reduced in the preliminary stage but then dramatically increased in advanced stage and these changes corresponded to a significant increase of Srx expression in the heart of diabetic rats. These time-dependent changes were also confirmed in neonatal cardiomyocytes and H9c2 cells treated with HG. Moreover, the reduction rate of hyperoxidized Prxs was greatly improved in the HG 24h group, which had an elevated expression of Srx. Our data also show that HG-induced AP1 activation and Srx expression were almost abolished by JNK inhibitor and N-acetylcysteine (NAC). In addition, siRNA-Srx suppressed HG-induced ANP and β-MHC gene expression. These observations suggest that activation of AP1 induced by HG is important for the expression of Srx and the reduction of hyperoxidized Prxs in cardiomyocytes. This Srx induction maybe is the pivotal compensatory protection mechanism against oxidative stress in diabetes or hyperglycaemia. Most interestingly, hyperoxidized Prxs/Srx pathway may be involved in the cardiac hypertrophy signaling of diabetes.


Fluctuations of backbone torsion angles obtained from NMR-determined structures and their prediction.
Protein molecules exhibit varying degrees of flexibility throughout their three-dimensional structures. Protein structural flexibility is often characterized by fluctuations in the Cartesian coordinate space. On the other hand, the protein backbone can be mostly defined by two torsion angles ϕ and ψ only. We introduce a new flexibility descriptor, backbone torsion-angle fluctuation derived from the variation of backbone torsion angles from different NMR models. The torsion-angle fluctuations correlate with mean-squared spatial fluctuations derived from the same collection of NMR models. We developed a neural-network based real-value predictor based on sequence information only. The predictor achieved ten-fold cross-validated correlation coefficients of 0.59 and 0.60, and mean absolute errors of 22.7° and 24.3° for the angle fluctuation of ϕ and ψ, respectively. This predictor is expected to be useful for function prediction and protein structure prediction when predicted torsion angles are used as restraints. Both sequence- and structure-based prediction of torsion-angle fluctuation will be available at http://sparks.informatics.iupui.edu within the SPINE-X package.


Platelet activation, P-selectin, and eosinophil β1-integrin activation in asthma.
Eosinophil β1-integrin activation correlates inversely with FEV1 and directly with eosinophil-bound P-selectin in subjects with nonsevere allergic asthma. Determine the relationships between β1-integrin activation and pulmonary function or eosinophil-bound P-selectin in subjects with asthma of varying severity and discern the source of eosinophil-bound P-selectin. Blood was assayed by flow cytometry for P-selectin and activated β1-integrin on eosinophils and platelets. Plasma was analyzed with ELISA for soluble P-selectin, platelet factor 4, and thrombospondin-1. Activated β1-integrin correlated with eosinophil-bound P-selectin among all subjects with asthma even though activated β1-integrin was higher in subjects with nonsevere asthma than severe asthma. Activated β1-integrin correlated inversely with FEV1 corrected for FVC only in younger subjects with nonsevere asthma. Paradoxically, platelet surface P-selectin, a platelet activation marker, was low in subjects with severe asthma, whereas plasma platelet factor 4, a second platelet activation marker, was high. Correlations indicated that P-selectin-positive platelets complexed to eosinophils are the major source of the eosinophil-bound P-selectin associated with β1-integrin activation. After whole-lung antigen challenge of subjects with nonsevere asthma, a model of asthma exacerbation known to cause platelet activation, circulating eosinophils bearing P-selectin and activated β1-integrin disappeared. The relationship between eosinophil β1-integrin activation and pulmonary function was replicated only for younger subjects with nonsevere asthma. However, we infer that platelet activation and binding of activated platelets to eosinophils followed by P-selectin-mediated eosinophil β1-integrin activation occur in both nonsevere and severe asthma with rapid movement of platelet-eosinophil complexes into the lung in more severe disease.


Considerations for Treating Nonobstetric Diseases in Pregnant Patients in the Emergency Department Setting.
To provide nonobstetric practitioners with an overview of key concepts for the pregnant patient and review treatment of 3 common acute nonobstetric diseases encountered in the emergency department setting. A literature search of PubMed was performed (1997-February 2023) using key search terms related to pregnancy, pain, urinary tract infection (UTI), venous thromboembolism (VTE), and anticoagulants. Relevant articles in English and humans were considered. When caring for a pregnant patient, it is important to utilize appropriate assessments, understand terms used in this population, and recognize how the physiological and pharmacokinetic changes that occur in pregnancy can influence medication use. Pain, UTIs, and VTE are common in this population. Acetaminophen is the most widely used medication for the management of pain during pregnancy and the drug of choice for mild pain in pregnancy not responsive to nonpharmacologic treatment. Pyelonephritis is the most common nonobstetric cause of hospitalization for pregnant patients. Antimicrobial treatment should consider maternal-fetal safety and local resistance patterns. Pregnant and postpartum patients have a 4- to 5-fold increased risk of developing a VTE compared with nonpregnant patients. Low-molecular-weight heparin is the preferred treatment. Pregnant patients often seek acute care in the emergency department setting for nonobstetric needs. Pharmacists in this setting should understand appropriate assessment questions and terms used within this population, the basics of physiological and pharmacokinetic changes in pregnancy that can impact treatment, and which resources are best to utilize for drug information of the pregnant patient. Practitioners in the acute care setting commonly encounter pregnant patients seeking care for nonobstetric concerns. This article covers key pregnancy-related information for the nonobstetric practitioner and focuses on the management of acute pain, UTI, and VTE during pregnancy.


TIPsy tour guides: how microtubule plus-end tracking proteins (+TIPs) facilitate axon guidance.
The growth cone is a dynamic cytoskeletal vehicle, which drives the end of a developing axon. It serves to interpret and navigate through the complex landscape and guidance cues of the early nervous system. The growth cone's distinctive cytoskeletal organization offers a fascinating platform to study how extracellular cues can be translated into mechanical outgrowth and turning behaviors. While many studies of cell motility highlight the importance of actin networks in signaling, adhesion, and propulsion, both seminal and emerging works in the field have highlighted a unique and necessary role for microtubules (MTs) in growth cone navigation. Here, we focus on the role of singular pioneer MTs, which extend into the growth cone periphery and are regulated by a diverse family of microtubule plus-end tracking proteins (+TIPs). These +TIPs accumulate at the dynamic ends of MTs, where they are well-positioned to encounter and respond to key signaling events downstream of guidance receptors, catalyzing immediate changes in microtubule stability and actin cross-talk, that facilitate both axonal outgrowth and turning events.


Pathologic Evaluation and Reporting of Carcinoma of the Penis.
Carcinoma of the penis is a rare tumor in the United States and in western European countries. Clinical management has become more complex in recent years, because organ-preserving strategies are being favored. Furthermore, our understanding of the pathogenesis of this malignancy has grown considerably. As a result of these developments, the demands on the pathology reports of surgical specimens from the penis have increased. There are also some peculiarities with the current World Health Organization and TNM classification systems of penile cancer as compared with other tumor entities. This review outlines the most relevant aspects that have to be considered in the pathologic handling and typing of penile carcinoma.


Hepatitis C virus infection among paediatric patients attending University of Assiut Hospital, Egypt.
Few studies have evaluated the epidemiology and risk factors of hepatitis C virus (HCV) infection in children in Egypt. This study of 465 children attending Assiut University Hospital measured the rates of anti-HCV positivity by 3rd-generation ELISA test and of HCV-RNA positivity by PCR, with analysis of some relevant risk factors. The rate of HCV-RNA positivity among ELISA-positive cases (n = 121) was 72.2% overall: 100% in the subgroup with hepatitis, 70.8% in those with a history of multiple transfusions and 58.3% in those without hepatitis or multiple transfusions. History of blood transfusions, frequent injections, hospitalization or surgical procedures were significant risk factors for anti-HCV positivity by ELISA.


In vivo and in vitro metabolism of cannabidiol monomethyl ether and cannabidiol dimethyl ether in the guinea pig: on the formation mechanism of cannabielsoin-type metabolite from cannabidiol.
Oxidative metabolism of cannabidiol monomethyl ether (CBDM), one of the components of marihuana, was studied in the guinea pig. Cannabielsoin monomethyl ether (CBEM) was found to be formed with hepatic microsomes by gas chromatography-mass spectrometry (GC-MS). Experiments using various modifiers of enzymatic reaction suggested that, as in the case of cannabielsoin (CBE) formation from canabidiol (CBD), CBEM was formed from CBDM by the monooxygenase system including cytochrome P450. When cannabidiol dimethyl ether (CBDD), in which phenolic hydroxyl groups of CBD are masked with methyl groups, was incubated with liver microsomes and an reduced nicotinamide adenine dinucleotide phosphate-generating system, 1S,2R-epoxy-CBDD was identified by GC-MS. The epoxy metabolite was also found in the liver of a guinea pig pretreated with CBDD (100 mg/kg, intraperitoneally) 1 h before sacrifice. Rate of 1S,2R-epoxide metabolism was slower than that of 1R,2S-epoxy-CBDD under the conditions, as in the microsomal oxidation of CBDD described above. These results indicate that 1S,2R-epoxides are formed from CBD, CBDM and CBDD and that the epoxides are quickly converted to elsoin-type metabolites in the cases of CBD and CBDM.


Mutations of the GLA gene in young patients with stroke: the PORTYSTROKE study--screening genetic conditions in Portuguese young stroke patients.
Fabry disease is an X-linked monogenic disorder caused by mutations in the GLA gene. Recent data suggest that stroke in young adults may be associated with Fabry disease. We aimed to ascertain the prevalence of this disorder among young adult patients with stroke in Portugal by GLA genotyping. During 1 year, all patients aged 18 to 55 years with first-ever stroke, who were admitted into any of 12 neurology hospital departments in Portugal, were prospectively enrolled (n=625). Ischemic stroke was classified according to Trial of Org 10172 in Acute Stroke Treatment criteria. Alpha-galactosidase activity was further assayed in all patients with GLA mutations. Four hundred ninety-three patients (mean age, 45.4 years; 61% male) underwent genetic analyses: 364 with ischemic stroke, 89 with intracerebral hemorrhage, 26 with subarachnoid hemorrhage, and 14 with cerebral venous thrombosis. Twelve patients had missense GLA mutations: 9 with ischemic stroke (p.R118C: n=4; p.D313Y: n=5), including 5 patients with an identified cause of stroke (cardiac embolism: n=2; small vessel disease: n=2; other cause: n=1), 2 with intracerebral hemorrhage (p.R118C: n=1; p.D313Y: n=1), and one with cerebral venous thrombosis (p.R118C: n=1). Leukocyte alpha-galactosidase activity was subnormal in the hemizygous males and subnormal or low-normal in the heterozygous females. Estimated prevalence of missense GLA mutations was 2.4% (95% CI, 1.3% to 4.1%). Despite a low diagnostic yield, screening for GLA mutations should probably be considered in different types of stroke. Restricting investigation to patients with cryptogenic stroke may underestimate the true prevalence of Fabry disease in young patients with stroke.


Cytochrome P450 1A induction in gudgeon Gobio gobio : Laboratory and Field Studies.
The induction of cytochrome P450 1A was studied in gudgeon (Gobio gobio), a common European cyprinid, using both farm-raised and field-caught fish. The effects of sex, reproductive status and past exposure to xenobiotics were assessed. When exposed to beta-naphthoflavone (bNF), reared gudgeon showed a dose-dependent increase of EROD activity with a plateau observed at doses from 20 mg kg-1 (females) and 5 mg kg-1 (males). The sexual difference in EROD activity was related to the gonadosomatic index (GSI) of the female whatever the level of induction. Dose and sex effects were confirmed by the immunodetection of CYP1A protein. More than 1 month was necessary for EROD activity to decrease to baseline levels. A second bNF injection after 32 days gave similar levels of induction, suggesting that EROD induction by bNF was not impaired by a pretreatment. Wild fish were brought from two sites in the Rhone river basin: a low contaminated site (Ain) and a highly contaminated site (Rhone). Wild gudgeon were highly induced by bNF in laboratory conditions, except males from the Rhone site which exhibited EROD levels as high as the EROD plateau found in laboratory conditions. A 2- month depuration period in clean water was necessary for EROD activity in wild gudgeon to decrease to baseline levels. These results provide better knowledge of the main factors of modulation of the induction in gudgeon as well as on the influence of the history of exposure to inducers.


Hydrogen adsorption on the indium-rich indium phosphide (001) surface: a novel way to produce bridging In-H-In bonds.
The indium phosphide (001) surface provides a unique chemical environment for studying the reactivity of hydrogen toward the electron-deficient group IIIA element, indium. Hydrogen adsorption on the In-rich delta(2 x 4) reconstruction produced a neutral, covalently bound bridging indium hydride. Using vibrational spectroscopy and ab initio cluster calculations, two types of bridging hydrides were identified, a (mu-H)In(2) and a (mu-H)(2)In(3) "butterfly-like" structure. These structures were formed owing to the large thermodynamic driving force for adsorption of H atoms on solid-state indium dimers.


Age-related changes in neocortical high-voltage spindles and alpha EEG power during quiet waking in rats.
Age-related changes in neocortical high-voltage spindle (HVS) and in electroencephalographic (EEG) alpha power were examined in young (3.0 to 4.6 months), middle-aged (10.2 to 13.8 months), and old (21.5 to 24.0 months) male Wistar rats during quiet waking. Whereas the duration of quiet waking stage did not change as a function of age, a significant increase in HVS amount and EEG alpha peak power was observed in the middle-aged rats with only a tendency for a further enhancement in the old animals. An additional analysis showed that the elevation of alpha power is associated with age rather than with HVS activity.


Phagocytic astrocytes: Emerging from the shadows of microglia.
Elimination of dead or live cells take place in both a healthy and diseased central nervous system (CNS). Dying or dead cells are quickly cleared by phagocytosis for the maintenance of a healthy CNS or for recovery after injury. Live cells or parts thereof, such as the synapses and myelin, are appropriately eliminated by phagocytosis to maintain or refine neural networks during development and adulthood. Microglia, the specific population of resident macrophages in the CNS, are classically considered as primary phagocytes; however, astrocytes have also been highlighted as phagocytes in the last decade. Phagocytic targets and receptors are reported to be mostly common between astrocytes and microglia, which raises the question of how astrocytic phagocytosis differs from microglial phagocytosis, and how these two phagocytic systems cooperate. In this review, we address the consequences of astrocytic phagocytosis, particularly focusing on these elusive points.


Depression symptoms among Omani children: age and sex differences.
The present study explored the existence of depressive symptoms among Omani children according to sex and age. The Arabic translated version of the Multidimensional Child and Adolescent Depression Scale was administered to 1,749 children (828 boys, 921 girls) ranging in age from 10 to 18 years old (M= 13.9, SD = 2.3) from 10 schools representing different areas of Muscat, Oman. The results showed no differences in the total mean scores on depression between boys and girls, although differences were observed on 4 of the 8 subscales. Boys had significantly higher scores on Weak concentration and Loneliness, while girls scored higher for Sleep problems and Anhedonia. Significant differences across ages also were exhibited for the total score as well as four subscales (Pessimism, Weak concentration, Anhedonia, and Fatigue), suggesting higher rates of depression among 15- to 18-year-olds.


Cascaded Excited-State Intramolecular Proton Transfer Towards Near-Infrared Organic Lasers Beyond 850 nm.
Near-infrared (NIR) organic solid-state lasers play an essential role in applications ranging from laser communication to infrared night vision, but progress in this area is restricted by the lack of effective excited-state gain processes. Herein, we originally proposed and demonstrated the cascaded occurrence of excited-state intramolecular proton transfer for constructing the completely new energy-level systems. Cascading by the first ultrafast proton transfer of <430 fs and the subsequent irreversible second proton transfer of ca. 1.6 ps, the stepwise proton transfer process favors the true six-level photophysical cycle, which supports efficient population inversion and thus NIR single-mode lasing at 854 nm. This work realizes longest wavelength beyond 850 nm of organic single-crystal lasing to date and originally exploits the cascaded excited-state molecular proton transfer energy-level systems for organic solid-state lasers.


Prevalence of antibiotic-resistant bacteria in herbal products.
The objective of this study was to determine the prevalence of antibiotic-resistant bacteria in various herbal products. Twenty-nine herbal supplements (18 traditional and 11 organic products) were purchased from stores and analyzed microbiologically. Total bacterial counts were determined by pour plate and surface spreading on tryptic soy agar (TSA). Antibiotic-resistant bacteria were enumerated on TSA supplemented with ceftriaxone (64 microg/ml) or tetracycline (16 microg/ml). Total bacterial counts ranged from <5 to 2.9 x 10(5) CFU/g. Ceftriaxone- and tetracycline-resistant bacteria were detected in ground garlic samples at 1.1 x 10(2) CFU/g and 3.0 x 102 CFU/g, respectively. Traditional and organic onion powder samples contained tetracycline-resistant bacteria at 17 and 28 CFU/g and ceftriaxone-resistant bacteria at 35 and 2.0 x 10(3) CFU/g, respectively. Other products such as ginger, rosemary, mustard, and goldenseal contained low levels of resistant bacteria. Fifty-two isolates were further evaluated against nine antibiotics, and the prevalence of antibiotic resistance was in the following order: ampicillin, nalidixic acid, trimethoprim, ceftriaxone, and streptomycin. Resistant bacteria were identified as Bacillus spp., Erwinia spp., and Ewingella americana. Staphylococcus spp., Enterobacter cloacae, and Stenotrophomonas maltophilia also were isolated. The presence of antibiotic-resistant bacteria and pathogens in these herbal products suggests that production and use of these products may need further evaluation.


Search for the pathogenic fungi in amniotic fluid.
Intra-amniotic infection with Candida is rare but considers an etiological factor for preterm rupture of membranes (PROM). The aim of the study was the investigation of the mycotic invasion of the amniotic cavity in pregnant women with PROM and with intact fetal memranes. 170 women were included in two groups: I (n = 150)--women with intact membranes; II (n = 20)--women with PROM. Samples of amniotic fluid were cultured on Sabouraud's medium. Fungal strains were isolated also from vagina, oral cavity and rectum of women with PROM. Intraamniotic infections were absent both in women with PROM and with intact membranes. Candida strains were isolated from vagina, oral cavity, and rectum in the group of women with PROM. Coexisting of multifocal Candida infections in pregnant women with PROM indicates that in those cases mycologic diagnosics should be recomended.


Hormonal treatment and psychological function during the menopausal transition: an evaluation of the effects of conjugated estrogens/cyclic medroxyprogesterone acetate.
To investigate the effect of hormone treatment on psychosocial distress of women during the menopausal transition (aged 40-52 years, still menstruating and with minor symptoms), in a study carefully designed to reduce bias and placebo effect. The study was randomized, controlled by placebo, blinded to the subject, investigators and biostatistician, crossed-over after 6 months, and evaluated by a 77-item questionnaire every month for 12 months. The medication tested was continuous conjugated estrogens (Premarin) and cyclic medroxyprogesterone acetate (Provera). Of an eligible 105 apparently healthy women, recruited by advertisement, 83 completed the questionnaires for the study. Randomization was successful. While there was a substantial variation over time in the change of scores for all the psychosocial outcomes, there was no significant difference between active and placebo treatment when order of treatment allocation was ignored. However, a strong and consistent effect of the order of treatment allocation for many of the scores was found; in particular, the effect of active treatment was substantially stronger when it was administered second. Positive effects of active treatment were found for the score for the overall symptom rating test (p < 0.009) and its components of depression and feeling of inadequacy (p = 0.011; p = 0.001, respectively). The use of hormones, given as a continuous estrogen and cyclic progestogen formulation after a formal calibration/run-in period, may have a beneficial effect on psychosocial distress experienced by women towards the end of their reproductive function.


Posterior Bite Collapse and Diagnostic Grading for Periodontitis.
The syndrome known as posterior bite collapse (PBC) has taken on multiple definitions over the years since its first introduction in 1964 by Morton Amsterdam and Leonard Abrams. In 2017, the World Workshop in the Classification of Periodontal and Peri-implant Diseases and Conditions proposed a staging system for periodontitis, defined by severity and extent of periodontal breakdown. Within this staging system, Stage IV periodontitis can include PBC. However, without a clear delineation regarding the clinical presentation or pathogenesis of PBC, this further obfuscates its definition. It is therefore the goal of this article to reexamine the original definition of PBC as defined by Amsterdam and Abrams, present an updated definition, and propose a clinical grading system of PBC to coincide with the 2017 staging of periodontitis.


Survey of Cochlear Implant User Satisfaction with the Neptune™ Waterproof Sound Processor.
A multi-center self-assessment survey was conducted to evaluate patient satisfaction with the Advanced Bionics Neptune™ waterproof sound processor used with the AquaMic™ totally submersible microphone. Subjective satisfaction with the different Neptune™ wearing options, comfort, ease of use, sound quality and use of the processor in a range of active and water related situations were assessed for 23 adults and 73 children, using an online and paper based questionnaire. Upgraded subjects compared their previous processor to the Neptune™. The Neptune™ was most popular for use in general sports and in the pool. Subjects were satisfied with the sound quality of the sound processor outside and under water and following submersion. Seventy-eight percent of subjects rated waterproofness as being very useful and 83% of the newly implanted subjects selected waterproofness as one of the reasons why they chose the Neptune™ processor. Providing a waterproof sound processor is considered by cochlear implant recipients to be useful and important and is a factor in their processor choice. Subjects reported that they were satisfied with the Neptune™ sound quality, ease of use and different wearing options.


Development of regional chemotherapies: feasibility, safety and efficacy in clinical use and preclinical studies.
Conventional oral and intravenous chemotherapies permeate throughout the body, exposing healthy tissues to similar cytotoxic drug levels as tumors. This leads to significant dose-limiting toxicities that may prevent patients from receiving sufficient treatment to overcome cancers. Therefore, a number of locoregional drug-delivery strategies have been evaluated and implemented in preclinical studies, clinical trials and in practice, in the past decades to minimize systemic toxicities from chemotherapeutic agents and to improve treatment outcomes. Localized treatment is beneficial because many cancers, such as melanoma, peritoneal cancer and breast cancer, advance locally adjacent to the site of the primary tumors prior to their circulatory invasion. In this article, we will review the feasibility, safety and efficacy of multiple localized chemotherapies in clinical use and preclinical development.