Mechanism of anti-inflammatory action of glycyrrhizin: effect on neutrophil functions including reactive oxygen species generation.
The effect of glycyrrhizin on inflammatory mediators such as neutrophil functions including reactive oxygen species (ROS) generation was examined. Glycyrrhizin significantly decreased neutrophil-generated O2-, H2O2 and OH in a dose-dependent manner. However, the drug did not reduce any of the ROS generated in a cell-free, xanthine-xanthine oxidase system. The drug did not affect neutrophil chemotaxis or phagocytosis, either. The present study indicates that glycyrrhizin is not an ROS scavenger but exerts an anti-inflammatory action by inhibiting the generation of ROS by neutrophils, the most potent inflammatory mediator at the site of inflammation.


Heading in soccer: is it safe?
Soccer is the world's game, played by 120 million people around the world and 16 million in the United States. It is unique in that it forbids the use of the upper extremity, other than by the goalkeeper or when throwing the ball into play from the sideline. It is also unique in that it is the only sport in which the head is purposefully used to strike the ball. As sports medicine has evolved, so has our curiosity about how certain sport-specific skills or protective equipment might change the injury profile of a sport. For soccer, there has been some concern that heading may be associated with the development of cumulative traumatic brain encephalopathy, or the "punch drunk" syndrome described in boxers. This article discusses this question in detail, with a critical look at the literature and an emphasis on the prospective data.


Neuroimaging in Closed Head Injury.
Closed head injury can be associated with significant neurologic dysfunction. Neuroimaging in this condition consists of conventional techniques such as computed tomography (CT) and magnetic resonance imaging (MR), and functional imaging studies such as single photon emission computerized tomography (SPECT) and positron emission tomography (PET). Whereas CT and MR are sufficient to show the acute concomitants of head trauma such as extra-axial hematomas, contusions, and shear injury, functional brain imaging has been shown to play an important role in management of victims of closed head injury, particularly in the chronic stages. Detection of changes in regional cerebral blood flow associated with brain injury have been found to correlate better with neurological status and prognosis than abnormalities seen by CT or MRI.


Molecular recognition templates of peptides: driving force for molecular evolution of peptide transporters.
Small peptides derived from protein hydrolysis occur ubiquitously. To utilize these structurally diverse compounds, organisms possess generic peptide transporters for di- (Dpp), tri- (Tpp), and oligopeptides (Opp). Using conformational analysis, we describe the predominant conformers of di-, tri-, and oligopeptides in water; dipeptides occur as nine main groups, defined by specific combinations of torsional angles. The molecular recognition templates (MRTs) of substrates for Dpp and Tpp comprise distinct groups of dipeptide conformers plus folded tripeptide conformers with matching spatial distribution of recognition features; for Opp, the MRT involves specific oligopeptide conformers with extended backbones. For any peptide, the proportion of its conformers in a particular MRT correlates with its relative binding and transport by each transporter. Thus, peptide transporters have evolved complementary specificities to optimize utilization of the universal peptide pool. The general applicability of MRTs should facilitate rational design and targeting of peptide-based prodrugs.


Quantitative proteomics discloses MET expression in mitochondria as a direct target of MET kinase inhibitor in cancer cells.
Cancer cells with MET overexpression are paradoxically more sensitive to MET inhibition than cells with baseline MET expression. The underlying molecular mechanisms are incompletely understood. Here, we have traced early responses of SNU5, a MET-overexpressing gastric cancer cell line, exposed to sublethal concentration of PHA-665752, a selective MET inhibitor, using iTRAQ-based quantitative proteomics. More than 1900 proteins were quantified, of which >800 proteins were quantified with at least five peptides. Proteins whose expression was perturbed by PHA-665752 included oxidoreductases, transfer/carrier proteins, and signaling proteins. Strikingly, 38% of proteins whose expression was confidently assessed to be perturbed by MET inhibition were mitochondrial proteins. Upon MET inhibition by a sublethal concentration of PHA-665752, mitochondrial membrane potential increased and mitochondrial permeability transition pore was inhibited concomitant with widespread changes in mitochondrial protein expression. We also showed the presence of highly activated MET in mitochondria, and striking suppression of MET activation by 50 nm PHA-665752. Taken together, our data indicate that mitochondria are a direct target of MET kinase inhibition, in addition to plasma membrane MET. Effects on activated MET in the mitochondria of cancer cells that are sensitive to MET inhibition might constitute a novel and critical noncanonical mechanism for the efficacy of MET-targeted therapeutics.


HALYS and QALYS and DALYS, Oh My: similarities and differences in summary measures of population Health.
Health-adjusted life years (HALYs) are population health measures permitting morbidity and mortality to be simultaneously described within a single number. They are useful for overall estimates of burden of disease, comparisons of the relative impact of specific illnesses and conditions on communities, and in economic analyses. Quality-adjusted life years (QALYs) and disability-adjusted life years (DALYs) are types of HALYs whose original purposes were at variance. Their growing importance and the varied uptake of the methodology by different U.S. and international entities makes it useful to understand their differences as well as their similarities. A brief history of both measures is presented and methods for calculating them are reviewed. Methodological and ethical issues that have been raised in association with HALYs more generally are presented. Finally, we raise concerns about the practice of using different types of HALYs within different decision-making contexts and urge action that builds and clarifies this useful measurement field.


Induction of circles of heterogeneous sizes in carcinogen-treated cells: two-dimensional gel analysis of circular DNA molecules.
Extrachromosomal circular DNA molecules are associated with genomic instability, and circles containing inverted repeats were suggested to be the early amplification products. Here we present for the first time the use of neutral-neutral two-dimensional (2D) gel electrophoresis as a technique for the identification, isolation, and characterization of heterogeneous populations of circular molecules. Using this technique, we demonstrated that in N-methyl-N'-nitro-N-nitrosoguanidine-treated simian virus 40-transformed Chinese hamster cells (CO60 cells), the viral sequences are amplified as circular molecules of various sizes. The supercoiled circular fraction was isolated and was shown to contain molecules with inverted repeats. 2D gel analysis of extrachromosomal DNA from CHO cells revealed circular molecules containing highly repetitive DNA which are similar in size to the simian virus 40-amplified molecules. Moreover, enhancement of the amount of circular DNA was observed upon N-methyl-N'-nitro-N-nitrosoguanidine treatment of CHO cells. The implications of these findings regarding the processes of gene amplification and genomic instability and the possible use of the 2D gel technique to study these phenomena are discussed.


Chimeric Epitope Vaccine from Multistage Antigens for Lymphatic Filariasis.
Lymphatic filariasis, a mosquito-borne parasitic disease, affects more than 120 million people worldwide. Vaccination for filariasis by targeting different stages of the parasite will be a boon to the existing MDA efforts of WHO which required repeated administration of the drug to reduce the infection level and sustained transmission. Onset of a filaria-specific immune response achieved through antigen vaccines can act synergistically with these drugs to enhance the parasite killing. Multi-epitope vaccine approach has been proved to be successful against several parasitic diseases as it overcomes the limitations associated with the whole antigen vaccines. Earlier results from our group suggested the protective efficacy of multi-epitope vaccine comprising two immunodominant epitopes from Brugia malayi antioxidant thioredoxin (TRX), several epitopes from transglutaminase (TGA) and abundant larval transcript-2 (ALT-2). In this study, the prophylactic efficacy of the filarial epitope protein (FEP), a chimera of selective epitopes identified from our earlier study, was tested in a murine model (jird) of filariasis with L3 larvae. FEP conferred a significantly (P < 0.0001) high protection (69.5%) over the control in jirds. We also observed that the multi-epitope recombinant construct (FEP) induces multiple types of protective immune responses, thus ensuring the successful elimination of the parasite; this poses FEP as a potential vaccine candidate.


An empowerment intervention for women living with HIV and its adaptation for women with a diagnosis of breast cancer.
Because of improved therapeutic strategies, both human immunodeficiency virus (HIV) infection and breast cancer can be considered life-threatening illnesses that eventually become a chronic condition. Both diagnoses carry a psychological impact, stigma, body alterations, intense medical evaluations, and therapies. Both conditions are prevalent among minorities, especially women of Hispanic heritage. This article describes an empowerment intervention originally designed for women living with HIV and adapted for women with a diagnosis of breast cancer. We will describe the conceptual framework for the intervention and the rationale for the chosen groups. The Women's Empowerment Intervention Model consists of a series of six full-day workshops in which multiple biopsychosocial dimensions are explored within the group, and diverse experiential activities are carried out related to the day's topics. The workshops were modified to deal with the specific issues that women confront when diagnosed with breast cancer. This model was chosen precisely because it deals with specific aspects of healing and living with a chronic illness. We propose that HIV should be viewed as a chronic condition and compared to other conditions that affect women's lives in similar ways.


Current and prospective applications of exosomal microRNAs in pulmonary fibrosis (Review).
Pulmonary fibrosis (PF) is a chronic, progressive, irreversible and life‑threatening lung disease. However, the pathogenesis and molecular mechanisms of this condition remain unclear. Extracellular vesicles (EVs) are structures derived from the plasma membrane, with a diameter ranging from 30 nm to 5 µm, that play an important role in cell‑to‑cell communications in lung disease, particularly between epithelial cells and the pulmonary microenvironment. In particular, exosomes are a type of EV that can deliver cargo molecules, including endogenous proteins, lipids and nucleic acids, such as microRNAs (miRNAs/miRs). These cargo molecules are encapsulated in lipid bilayers through target cell internalization, receptor‑ligand interactions or lipid membrane fusion. miRNAs are single‑stranded RNA molecules that regulate cell differentiation, proliferation and apoptosis by degrading target mRNAs or inhibiting translation to modulate gene expression. The aim of the present review was to discuss the current knowledge available on exosome biogenesis, composition and isolation methods. The role of miRNAs in the pathogenesis of PF was also reviewed. In addition, emerging diagnostic and therapeutic properties of exosomes and exosomal miRNAs in PF were described, in order to highlight the potential applications of exosomal miRNAs in PF.


Nursing research and participant recruitment: organizational challenges and strategies.
Hospitals as research environments are crucial in advancing evidence-based practice and translational research. The authors discuss issues related to hospital-based nursing research such as institutional review board approval, the HIPAA, structure, unit characteristics, and nurse staffing as well as research-related issues such as study purpose and design, participant recruitment, and research personnel. Strategies and suggestions for nurse executives to assist researchers in overcoming recruitment challenges are presented.


Emergency preparedness for home healthcare providers.
Unfortunately, disasters occur. We cannot always know the effects ahead of time, but we do know that lives can be lost, property damaged, and public health and home care agencies may not be able to provide the normal standard of care. Studies have shown that disaster preparedness content is limited in U.S. nursing programs (). Given the magnitude of recent natural disasters, such as the Japanese earthquake and tsunami in 2011, these findings are alarming. The increasing demands on healthcare providers in response to emergencies force home healthcare clinicians to identify their roles and responsibilities in emergency preparedness. This article discusses 1 model of disaster response and the role of the home healthcare provider at each stage. It further guides home healthcare nurses in creating a personal and professional plan, enabling them to understand how to minimize the impact of disasters and address the needs of their patients and those close to them.


Preparation of solid dispersion for ethenzamide-carbopol and theophylline-carbopol systems using a twin screw extruder.
In the present study, we prepared solid dispersions of water-insoluble and soluble drugs (ethenzamide (ETZ) and theophylline (THEO)) by the twin screw extruder method, which made it possible to control both kneading and heating at the same time under the fusion point of each drug, using three types of the controlled-release high-molecular-weight substance Carbopol (CAR) as the carrier. The solid dispersions obtained were evaluated and compared with those prepared by the organic solvent method. These products showed significantly increased solubility of ETZ, but the solubility of THEO was reduced indicating that CAR slows the release of THEO. It is important not only to simply knead under high pressure but to select the optimal operation temperature to bring these drugs into a semi-fusion state. Solid dispersions obtained by this method showed X-ray diffraction and differential scanning calorimetry (DSC) patterns similar to those obtained by the organic solvent method indicating that the former can be used as a simple and effective method for preparation of solid dispersions.


Body-composition changes in patients who gain weight while receiving megestrol acetate.
Randomized placebo-controlled clinical trials have now established that megestrol acetate causes appetite stimulation and weight gain in patients with anorexia and/or cachexia. There is a paucity of available data to delineate the substance of this increased weight. Using dual-energy x-ray absorptiometry and tritiated body water methodologies, we performed body-composition measurements in 12 patients with advanced cancer before the institution of oral megestrol acetate (800 mg/d) and at subsequent 2-month intervals. Seven of the 12 patients gained weight (2.1 to 16.5 kg) and had repeat body-composition measurements performed at the time of maximum weight gain. The vast majority of the gained weight was clearly from an increase in adipose tissue, while there was a suggestion that an increase in body fluid was responsible for a minority of the weight gain. Megestrol acetate-induced weight gain is primarily the result of an increase in body mass.


International allied health student placements: A meta-synthesis.
Increasingly universities are offering international student placements as part of the global internationalisation movement. This review sought to synthesize the findings of studies to further understand the learning outcomes described by allied health students. To contribute to the understanding of the learning outcomes described by allied health students who have undertaken an international placement. A qualitative meta-synthesis was conducted. From six databases, twenty-one studies were identified and critically appraised. Data were meta-aggregated, integrated and interpreted to develop new themes, with the experiences of over 259 allied health students synthesized. Themes include: the intertwined personal and professional development experienced by the students; confidence and independence, relationship building, insight into culture, service provision and differences in socio-economic and political contexts. Universities offering students international placements provide their students with opportunities to achieve unique learning outcomes with significant personal and professional transformational development that cannot be replicated by local placements.


Health Behaviour Changes of Cutaneous Melanoma Survivors in Slovenia - A Qualitative Study.
Most data related to cutaneous melanoma survivors' health behaviour comes from epidemiological studies and is predominantly concerned with safe-sun behaviour and self-examination. Data regarding other changes of health behaviour are scarce and so are qualitative studies in this realm. The aim of our research is to acquire insight into the experiences of patients with cutaneous melanoma in Slovenia. How did they react to the diagnosis, which changes did they introduce in their health behaviour and how do they assess the role of family doctors? Using the qualitative approach of collective case reports, a demographically diverse group of patients with different forms and stages of cutaneous melanoma was selected. Semi-structured interviews conducted by a psychologist were recorded and transcribed verbatim. For data processing, the approach of Qualitative Content Analysis was applied. We integrated interviewees' experiences after the diagnosis of cutaneous melanoma in several subcategories: either they did not introduce any changes or they mentioned changing their habits when exposed to the sun and performing skin self-examination; they also emphasized their ways of dealing with stress and raising awareness about melanoma among family members and friends. The role of family doctors in the prevention and care appears unclear; even contradictory. We obtained insight into the experiences of Slovenian patients with cutaneous melanoma. The interviewees prioritised safe behaviour in the sun, strengthening of psychological stability and raising awareness about melanoma. Findings will be used in the creation of a structured questionnaire for national epidemiological survey.


Rifaximin protects SH-SY5Y neuronal cells from iron overload-induced cytotoxicity via inhibiting STAT3/NF-κB signaling.
Acute or chronic liver disease-caused liver failure is the cause of hepatic encephalopathy (HE), characterized by neuropsychiatric manifestations. Liver diseases potentially lead to peripheral iron metabolism dysfunction and surges of iron concentration in the brain, contributing to the pathophysiological process of degenerative disorders of the central nervous system. In this study, the mechanism of rifaximin treating HE was investigated. Ferric ammonium citrate (FAC)-induced iron overload significantly reduced the proliferation and boosted the apoptosis in SH-SY5Y cells through increasing reactive oxygen species (ROS) levels and inducing iron metabolism disorder. Rifaximin treatment could rectify the FAC-induced iron overload and lipopolysaccharide (LPS)-induced iron deposition, therefore, effectively protecting SH-SY5Y cells from ROS-induced cell injury and apoptosis. Signal transducer and activator of transcription 3 (STAT3)/nuclear factor-kappa B (NF-κB) signaling is involved in the protective function of rifaximin against LPS-induced iron deposition. The therapeutic effect of rifaximin on HE associated with acute hepatic failure in mouse model was ascertained. In conclusion, Rifaximin could effectively protect SH-SY5Y cells against injury caused by iron overload through the rectification of the iron metabolism disorder via the STAT3/NF-κB signaling pathway.


Computer content analysis of the Schreber case.
The text of Schreber's Memoirs of My Nervous Illness was analyzed by computer at the level of the individual word. These words then were grouped into 17 rational categories, and the categories were checked for reliability. The contents of Schreber's work then were compared with three other documents. In general, the Memoirs showed much greater delusional content than the other documents. Interestingly, sexual matters did not appear to be Schreber's principal problem at this atomistic level.


A host-specific function is required for ligation of a wide variety of ribozyme-processed RNAs.
Hepatitis delta virus (HDV) replicates its circular RNA genome via a rolling circle mechanism. During this process, cis-acting ribozymes cleave adjacent upstream sequences and thereby resolve replication intermediates to unit-length RNA. The subsequent ligation of these 5'OH and 2',3'-cyclic phosphate termini to form circular RNA is an essential step in the life cycle of the virus. Here we present evidence for the involvement of a host activity in the ligation of HDV RNA. We used both HDV and hammerhead ribozymes to generate a panel of HDV and non-HDV RNA substrates that bear 5' hydroxyl and 2', 3'- cyclic phosphate termini. We found that ligation of these substrates occurred in host cells, but not in vitro or in Escherichia coli. The host-specific ligation activity was capable of joining RNA in both bimolecular and intramolecular reactions and functioned in a sequence-independent manner. We conclude that mammalian cells contain a default pathway that efficiently circularizes ribozyme processed RNAs. This pathway could be exploited in the delivery of stable antisense and decoy RNA to the nucleus.


Bronchiectasis in a child after acrolein inhalation.
Acrolein is an unsaturated aldehyde produced by combustion of many organic compounds. Massive exposure may lead to severe pulmonary disease and possibly death. We report a case of intoxication in a 2-year-old boy; an 18-month follow-up showed development of obstructive bronchiolar disease with diffuse bronchiectasis.


The axonal repellent Slit2 inhibits pericyte migration: potential implications in angiogenesis.
The Slit family of secreted proteins acts through the Roundabout (Robo) receptors to repel axonal migration during central nervous system development. Emerging evidence shows that Slit/Robo interactions also play a role in angiogenesis. The effect of Robo signaling on endothelial cells has been shown to be context-dependent. However, the role of Slit/Robo in pericytes has been largely unexplored. The aim of this study was to determine the effect of Slit2 on primary human pericytes and to address the underlying mechanisms, including the receptors potentially implicated. We demonstrate that both Robo1 and Robo4 are expressed by human pericytes. In the presence of their ligand Slit2, spontaneous and PDGF-induced migration of pericytes was impaired. This antimigratory activity of Slit-2 correlated with the inhibition of actin-based protrusive structures. Interestingly, human pericyte interaction with immobilized Slit2 was inhibited in the presence of anti-Robo1 and anti-Robo4 blocking antibodies, suggesting the implication of both receptors. These results add new insights into the role of Slit proteins during the angiogenic process that relies on the directional migration not only of endothelial cells but also of pericytes.


Herceptin-conjugated liposomes co-loaded with doxorubicin and simvastatin in targeted prostate cancer therapy.
Prostate cancer (PCa) is a leading cause of cancer-related deaths among men. The anthracycline doxorubicin (DOX) is used for the treatment of this disease, but its considerable side effects and non-selectivity are major drawbacks. Simvastatin (Sim), a lipid-lowering agent, holds great promise as a cancer therapeutic, and thus could be used in combination with DOX. Targeted drug-loaded nano-carriers with antibodies for receptors that are overexpressed on tumor cells are promising strategies for decreasing toxicity to normal tissues and enhancing the efficacy of chemotherapies in cancer treatment. Specifically, human epidermal growth factor 2 is overexpressed and constitutively activated in the PC-3 cell line. Within this context, we designed a co-delivery system coated with Herceptin for PCa, performed physicochemical characterizations, and tested the formulations for cytotoxicity and uptake. The targeted liposomes had a mean particle size of 134 nm, and the drug encapsulation efficiency of both Sim and DOX were greater than 80%. We discovered that the drug combination led to the strong inhibition of PCa both in vitro and in vivo, with inhibitory rates of tumor volumes corresponding to 80.36% and 68.77% of Herceptin-coated liposomes and non-targeted liposomes, respectively. We also found that the anti-tumor mechanisms of the DOX and Sim combination were possibly attributed to synergistic anti-angiogenesis. These results reveal that Herceptin-conjugated liposomes co-loaded with DOX and Sim are a potential novel therapeutic strategy for overcoming PCa.


Repurposing Disulfiram for Targeting of Glioblastoma Stem Cells: An In Vitro Study.
Mesenchymal glioblastoma stem cells (GSCs), a subpopulation in glioblastoma that are responsible for therapy resistance and tumor spreading in the brain, reportedly upregulate aldehyde dehydrogenase isoform-1A3 (ALDH1A3) which can be inhibited by disulfiram (DSF), an FDA-approved drug formerly prescribed in alcohol use disorder. Reportedly, DSF in combination with Cu2+ ions exerts multiple tumoricidal, chemo- and radio-therapy-sensitizing effects in several tumor entities. The present study aimed to quantify these DSF effects in glioblastoma stem cells in vitro, regarding dependence on ALDH1A3 expression. To this end, two patient-derived GSC cultures with differing ALDH1A3 expression were pretreated (in the presence of CuSO4, 100 nM) with DSF (0 or 100 nM) and the DNA-alkylating agent temozolomide (0 or 30 µM) and then cells were irradiated with a single dose of 0-8 Gy. As read-outs, cell cycle distribution and clonogenic survival were determined by flow cytometry and limited dilution assay, respectively. As a result, DSF modulated cell cycle distribution in both GSC cultures and dramatically decreased clonogenic survival independently of ALDH1A3 expression. This effect was additive to the impairment of clonogenic survival by radiation, but not associated with radiosensitization. Of note, cotreatment with temozolomide blunted the DSF inhibition of clonogenic survival. In conclusion, DSF targets GSCs independent of ALDH1A3 expression, suggesting a therapeutic efficacy also in glioblastomas with low mesenchymal GSC populations. As temozolomide somehow antagonized the DSF effects, strategies for future combination of DSF with the adjuvant standard therapy (fractionated radiotherapy and concomitant temozolomide chemotherapy followed by temozolomide maintenance therapy) are not supported by the present study.


Willingness to pay for community delivery of antiretroviral treatment in urban Tanzania: a cross-sectional survey.
Community health worker (CHW)-led community delivery of HIV antiretroviral therapy (ART) could increase ART coverage and decongest healthcare facilities. It is unknown how much patients would be willing to pay to receive ART at home and, thus, whether ART community delivery could be self-financing. Set in Dar es Salaam, this study aimed to determine patients' willingness to pay (WTP) for CHW-led ART community delivery. We sampled ART patients living in the neighbourhoods surrounding each of 48 public-sector healthcare facilities in Dar es Salaam. We asked participants (N = 1799) whether they (1) preferred ART community delivery over standard facility-based care, (2) would be willing to pay for ART community delivery and (3) would be willing to pay each of an incrementally increasing range of prices for the service. 45.0% (810/1799; 95% CI: 42.7-47.3) of participants preferred ART community delivery over standard facility-based care and 51.5% (417/810; 95% CI: 48.1-55.0) of these respondents were willing to pay for ART community delivery. Among those willing to pay, the mean and median amount that participants were willing to pay for one ART community delivery that provides a 2-months' supply of antiretroviral drugs was 3.61 purchasing-power-parity-adjusted dollars (PPP$) (95% CI: 2.96-4.26) and 1.27 PPP$ (IQR: 1.27-2.12), respectively. An important limitation of this study is that participants all resided in neighbourhoods within the catchment area of the healthcare facility at which they were interviewed and, thus, may incur less costs to attend standard facility-based ART care than other ART patients in Dar es Salaam. While there appears to be a substantial WTP, patient payments would only constitute a minority of the costs of implementing ART community delivery. Thus, major co-financing from governments or donors would likely be required.


Selective inhibition of enzyme synthesis by lincomycin in Staphylococcus aureus.
The effect of subinhibitory concentrations of lincomycin on the production of lipase, coagulase and alpha-haemolysin by one lincomycin-resistant strain of Staphylococcus aureus was investigated. The highest concentration of lincomycin, which had little effect on growth, completely inhibited enzyme and haemolysin formation. The antibiotic at the concentrations used did not inactivate enzymes. Lincomycin caused no intracellular accumulation of these products, indicating a possible effect on enzyme and haemolysin synthesis. Subinhibitory concentrations of erythromycin and chloramphenicol showed no effect on enzyme and haemolysin formation.


The Use of the Social Cognition and Object Relations Scale in a Primary Care Setting.
Research has indicated that as many as 10% to 15% of primary care patients have symptoms that are not well explained medically. These patients could be labeled as "somatizers." This study assessed the extent to which underlying psychological characteristics contribute to a person's level of somatization and service utilization. The Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G; Stein, Hilsenroth, Slavin-Mulford, & Pinsker, 2011; Westen, 1995) was used to rate early memory narratives of 100 patients in a suburban primary care setting. Using principal axis factoring, the SCORS-G was divided into 2 components and these components (cognitive and affective) were used in subsequent analyses. The affective component was significantly negatively correlated with 2 measures of somatization and positively related to physician ratings of global health. The affective component also showed a trend toward significance on overnight hospital stays and patient-rated health. The cognitive component showed a trend toward significance with both measures of somatization, but it was not correlated with other measures of health. This study demonstrates the value of assessing underlying processes (via SCORS-G ratings of early memory narratives) that contribute to increased rates of somatization and health care utilization. Clinical implications for the relationship between affect and physical health are explored.


Long Non-Coding RNA HCG11 Inhibits Glioma Cells Proliferation and Migration through Decoying miR-590-3p and Up-Regulating CADM2.
Long non-coding RNAs are reportedly endowed with the function of promoting or inhibiting cancer occurrence and development. The emphasis of this study was placed on the effect of lncRNA HLA complex group 11 (HCG11) on glioma progression, as well as its mechanism. Quantitative real-time polymerase chain reaction was utilized for detecting HCG11, miR-590-3p, and CAMD2 mRNA expression levels in glioma tissues. Western blot was adopted to examine cell adhesion molecule (CADM2) protein expression. Cell counting kit-8, BrdU, Transwell and wound healing assays were employed for investigating the malignant biological behaviors of glioma cells. RNA immunoprecipitation assay and dual-luciferase reporter assay were performed to prove the relationship between miR-590-3p and HCG11, as well as CADM2 and miR-590-3p. HCG11 expression was lower in glioma tissues compared with that in paracancerous tissues, and its expression level was negatively correlated with WHO tumor stage. In addition, compared with in astrocyte cell line, the expression of HCG11 was lower in glioma cells. Functional experiments showed that HCG11 inhibited glioma cells migration and proliferation, while miR-590-3p facilitated these processes. Acting as a competitive endogenous RNA, HCG11 adsorbed miR-590-3p and upregulated the expression of CADM2, the target gene of miR-590-3p. HCG11 suppresses glioma cells proliferation and migration through regulating the miR-590-3p/CADM2 molecular axis.


Analysis of muscle activation in lower extremity for static balance.
Balance plays an important role for human bipedal locomotion. Degeneration of balance control is prominent in stroke patients, elderly adults and even for majority of obese people. Design of personalized balance training program, in order to strengthen muscles, requires the analysis of muscle activation during an activity. In this paper we have proposed an affordable and portable approach to analyze the relationship between the static balance strategy and activation of various lower extremity muscles. To do that we have considered Microsoft Kinect XBox 360 as a motion sensing device and Wii balance board for measuring external force information. For analyzing the muscle activation pattern related to static balance, participants are asked to do the single limb stance (SLS) exercise on the balance board and in front of the Kinect. Static optimization to minimize the overall muscle activation pattern is carried out using OpenSim, which is an open-source musculoskeletal simulation software. The study is done on ten normal and ten obese people, grouped according to body mass index (BMI). Results suggest that the lower extremity muscles like biceps femoris, psoas major, sartorius, iliacus play the major role for both maintaining the balance using one limb as well as maintaining the flexion of the other limb during SLS. Further investigations reveal that the higher muscle activations of the flexed leg for normal group demonstrate higher strength. Moreover, the lower muscle activation of the standing leg for normal group demonstrate more headroom for the biceps femoris-short-head and psoas major to withstand the load and hence have better static balance control.


Aldosterone causes DNA strand breaks and chromosomal damage in renal cells, which are prevented by mineralocorticoid receptor antagonists.
Epidemiological studies exploring the connection between hypertension and cancer incidence find a higher cancer mortality in hypertensive patients, particularly elevated in hypertension associated with a stimulation of the renin-angiotensin-aldosterone system. Primary aldosteronism, with plasma aldosterone levels between 0.5 and 1 nM (18-36 ng/dL) and local aldosterone levels up to 500 nM (18,000 ng/dL), is now recognised as a more common cause for hypertension. We recently found angiotensin II to be genotoxic due to its induction of oxidative stress. Since aldosterone in higher concentrations also has oxidative effects, its potential genotoxic action in pig LLC-PK1 cells with properties of proximal tubules was analysed. DNA damage was evaluated by two test systems: the comet assay, and the micronucleus frequency test. The results showed that aldosterone concentrations starting from 10 nM (360 ng/dL) caused a significant increase of DNA damage monitored with the comet assay in LLC-PK1, while there was no change in cell vitality and proliferation. The micronucleus frequency test revealed that 10 nM aldosterone also leads to the formation of micronuclei. Furthermore, the formation of superoxide radicals in the cells by this aldosterone concentration could be detected with the superoxide-specific stain dihydroethidium. Further evidence for oxidative stress-induced DNA damage was its reversibility by the antioxidants tempol and catalase. Addition of the steroidal mineralocorticoid receptor antagonist spironolactone or the novel selective nonsteroidal antagonist (R)-BR-4628 reduced the DNA damage and the amount of superoxide radicals indicating a receptor-dependent process.


Primary magnetic resonance imaging/ultrasonography fusion-guided biopsy of the prostate.
To examine the performance of a primary magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided targeted biopsy (TB), and in combination with an added systematic biopsy (SB). Analysis of 318 consecutive biopsy-naïve men with suspicious multiparametric MRI (mpMRI; Prostate Imaging Reporting and Data System [PI-RADS] score ≥3) undergoing transrectal TB and 10-core SB between January 2012 and December 2016. The indication for performing mpMRI was based on clinical parameters and decided by the treating urologist before admission. TB was performed with a sensor-based MRI/US fusion-guided platform. Clinically significant prostate cancer was defined as Gleason score ≥4 + 3 = 7 (International Society of Urological Pathology Grade [ISUP] grade 3) or maximum cancer core length of ≥6 mm. A median (interquartile range) of 14 (13-14) biopsies per case were taken. The overall cancer detection rate (CDR) was 77% (245/318). The TB alone detected 67% of prostate cancers and the SB alone detected 70%. The PI-RADS dependent CDR for the combination of TB/SB were 38% (21/55), 78% (120/154) and 95% (104/109) for PI-RADS scores of 3/4/5, respectively. Clinically significant prostate cancer was diagnosed by the combination of TB and SB in 195 men (61%) and by TB alone in 163 cases (51%). The number of missed or underestimated prostate cancers with a Gleason score ≥8 for TB alone was 31 (10%, P < 0.001) and 21 (7%, P < 0.001) for SB alone in comparison with the results of the combination of TB and SB. The rate of insignificant prostate cancer was comparable for the combination of TB and SB and TB alone (50/318, 16% vs 50/318, 16%). Pre-biopsy mpMRI is of incremental value in increasing the detection of clinically significant prostate cancer in biopsy-naïve patients with suspicion of prostate cancer. Combining TB with SB further improved the diagnostic accuracy without increasing the rate of insignificant prostate cancer.


Comparative physiology on "the lung controls the skin and hair".
"The lung is connected with skin and hair" is a theory of traditional Chinese medicine. From the view of comparative physiology we researched the inter-relation of lung and skin and hair and found it in water. From living protein to fish respiration is by the structure corresponding to the skin and the organ which originated skin. Though amphibia have lung respiratory effect of skin still locate 2/3. Aves. Mammals and human beings use lungs to respire. In fact air exchanges from nature through the thin water molecular layer of the surface of the pulmonary alveoli. So the lung is derived from "skin and hair" to adapt to inter-respiration.


[Unprotected sexual behaviors and related factors of HIV-positive MSM with multiple sexual partners].
This study aimed to investigate the status of multiple sexual partners and unprotected sexual behaviors and related influencing factors among HIV-positive men who have sex with men (MSM). HIV-positive men having sex with men aged 18 years or older, living in Chengdu, Chongqing or Guangzhou were recruited by using the " snowballing" sampling method. Participants completed the questionnaire on computers, after filling in the Informed Consent Form. Content of the study would include social demographic characteristics, number of sexual partners, sexual behaviors, and the symptoms assessment on depression and anxiety.χ(2)-test,t-test and non-conditional Multiple logistic Regression methods were used to examine the risky sexual behaviors with multiple sexual partners among the participants engaged in this project. Mean age of the 501 participants was (30.24±7.70) years old. In the past 6 months, 17.4% (87/501) of them had engaged in unprotected sexual behavior with two or more sexual partners. Factors at risk would include: being married (OR=1.93, 95%CI: 0.77-4.84), divorced or widowed (OR=3.94, 95%CI: 1.66-9.36), having primary male sexual partners (OR=5.04, 95%CI: 1.08-23.54) and casual or commercial male sexual partners (OR=2.54, 95%CI: 1.34-4.80) in the past 6 months, drinking alcohol (OR=3.00, 95%CI: 1.37-6.62) or Rush (alkyl nitrite) (OR=3.53, 95%CI: 1.72-7.23) during sexual acts, sharing their HIV-infection status to their partly primary male sexual partners (OR=1.84, 95%CI:0.78-4.33) or not (OR=2.68, 95% CI: 1.25-5.73), and having high sexual sensation seeking scores (OR=1.09, 95%CI: 1.03-1.15). Unprotected sexual behaviors with multiple sexual partners among HIV-positive MSM played an important role in expediting the HIV transmission. Development of intervention programs to minimize the risk sexual behaviors and setting up efficient medical and biological measures in controlling the HIV transmission were in urgent need.


Combination of Chemically-Characterized Essential Oils from Eucalyptus polybractea, Ormenis mixta, and Lavandula burnatii: Optimization of a New Complete Antibacterial Formulation Using Simplex-Centroid Mixture Design.
This study aims to identify the volatile profile of three essential oils obtained from Eucalyptus polybractea cryptonifera (EPEO), Ormenis mixta (OMEO), and Lavandula burnatii briquet (LBEO) and to examine their combined antibacterial activity that affords the optimal inhibitory ability against S. aureus and E. coli using simplex-centroid mixture design and checkerboard assay. Essential oils (EOs) were isolated by hydrodistillation and characterized using gas chromatography-mass spectrometry (GC-MS) and gas chromatography coupled with flame-ionization detector (GC-FID). The antibacterial activity was performed using disc diffusion and microdilution assays. The chemical analysis revealed that 1,8-cineole (23.75%), p-cymene (22.47%), and α-pinene (11.20%) and p-menthane-1,8-diol (18.19%), α-pinene (10.81%), and D-germacrene (9.17%) were the main components detected in E. polybractea and O. mixta EOs, respectively. However, L. burnatii EO was mainly represented by linalool (24.40%) and linalyl acetate (18.68%). The EPEO, LBEO, and OMEO had a strong antibacterial effect on S. aureus with minimal inhibitory concentrations (MICs) values ranging from 0.25 to 0.5% (v/v). Furthermore, the combination of 1/2048 MICEPEO + 1/4 MICLBEO showed a synergistic antibacterial effect on S. aureus with a FIC index of 0.25, while the formulation of 1/4 MICEPEO + 1/4 MICOMEO demonstrated an antibacterial synergistic activity on E. coli with a FIC index of 0.5. Moreover, the simplex-centroid mixture design reported that the most effective combinations on E. coli and S. aureus correspond to 32%/28%/40% and 35%/30%/35% of E. polybractea, O. mixta, and L. burnatii, respectively. Presented information highlights the action of antibacterial formulations of these EOs and suggests their potential applications as alternatives to commercialized drugs to contract the development of bacteria causing serious infections and food deterioration.


Synergistic effect of mechanical stretch and angiotensin II on superoxide production via NADPH oxidase in vascular smooth muscle cells.
Mechanical forces and angiotensin II influence the structure and function of vascular cells, and play an important role in reactive oxygen species production. In this study, we examined the effects of mechanical stretch and angiotensin II on the expression of p22-phox and Nox-1, essential membrane components of NADPH oxidase, and superoxide production in rat vascular smooth muscle cells (VSMCs). Neither a stretch force nor angiotensin II alone altered p22-phox and Nox-1 expression in VSMCs. Combined stimulation markedly increased p22-phox and Nox-1 mRNA, however, which was associated with increased NADPH oxidase activity, superoxide production and total 8-iso-prostaglandin F2alpha concentration. The increases in p22-phox mRNA levels induced by a stretch force in combination with angiotensin II were prevented by treatment with an angiotensin type I (AT1) receptor antagonist, RNH-6270 (100 nmol/l). Protein expression of the AT1 receptor was upregulated by a stretch force. These data indicate that mechanical stretch and angiotensin II synergistically increase NADPH oxidase expression in VSMCs, and suggest that part of this mechanism is mediated through an upregulation of the AT1 receptor induced by mechanical stretch. The combined effects of mechanical strain and angiotensin II might promote vascular damage through the production of superoxide in a hypertensive state.


Neuroscience and psychoanalysis: approaches to consciousness and thinking.
There exists an enormous amount of biological and scientific data in the field of neuroscience, which are daunting and laborious to those who are not directly engaged in these specialized areas. The intricacies and complexities of the role of the central nervous system (CNS) in psychiatric disorders and human behavior are, of course, acknowledged. In this article, observations and speculations of some prominent workers in the field of neuroscience are described with focus on their conclusions, rather than specific findings as they pertain to the mind-body relationship. The mind-brain/body issue has not been resolved insofar as clarifying the connections between CNS activity and thinking is concerned. Currently, it is useful to accept the concept of parallelism between CNS activity and thought. An argument will be made for the inclusion of the psychoanalytic method as an essential component of the scientific effort to elucidate consciousness and thinking.


[Clinical observation on adoptive immunotherapy with autologous cytokine-induced killer cells for advanced malignant tumor].
Cytokine-induced killer (CIK) cells have the characteristics of rapid proliferation, high efficiency, and broad spectrum in killing of tumor cells. However, there was few report about its clinical application on treatment for cancer patients. The current study was designed to evaluate the effect of adoptive transfer of autologous CIK cells on the patients with advanced malignant tumor. Peripheral blood mononuclear cells of the patients with advanced malignant tumor were separated by fractionation on Ficoll-Hypaque gradient, then cultured in the medium containing IFN-gamma, IL-2, and CD3McAb for 7 days in vitro, and than the cultured auto-CIK cells were transfused back to the patients. The numbers of transferred CIK cells per patient were 5-15 x 10(9) in one course of treatment. Among these patients, 47 cases received chemotherapy, 3 cases received radiotherapy before CIK cells transfusion. The interval between chemoradiotherapy and immunotherapy was over 2 to 4 weeks. Among 63 patients receiving CIK cells immunotherapy, the total effective rate (PR + MR) was 44.46% (28). In the patients with increasing of CEA level in serum, 14 cases showed reduction of serum CEA and 1 cases remained increasing after the treatment with CIK cell. In the patients with increasing of AFP level in serum, similarly, 9 cases showed reduction of serum AFD and 1 case remained increasing. The absolute members of CD3, CD4, and CD8T cells increased to over 45% after being treated with CIK cells. Among treated patients, the appetite of 51 cases and performance and sleep of 32 cases got improved. Among 18 cases, 13 cases showed the pain relief. Adoptive immunotherapy of auto-CIK cells can significantly enhance cellular immune functions and improve subjective symptoms, but without side effects, so this is a safe and effective treatment for the patients with malignant tumor.


Structural characterization of epitaxial Cr(x)Mo(1-x) alloy thin films.
To develop a model system containing regularly spaced misfit dislocations for studies of the radiation resistance of nanoscale defects, epitaxial thin films of Cr, Mo, and Cr(x)Mo(1-x) alloys were deposited on MgO(001) by molecular beam epitaxy. Film compositions were chosen to vary the lattice mismatch with MgO. The film structure was investigated by x-ray diffraction (XRD), Rutherford backscattering spectrometry (RBS) and scanning transmission electron microscopy (STEM). Epitaxial films with reasonably high crystalline quality and abrupt interfaces were achieved at a relatively low deposition temperature, as confirmed by STEM. However, it was found by XRD and RBS in the channeling geometry that increasing the Mo content of the CrMo alloy films degraded the crystalline quality, despite the improved lattice match with MgO. XRD rocking curve data indicated that regions of different crystalline order may be present within the films with higher Mo content. This is tentatively ascribed to spinodal decomposition into Cr-rich and Mo-rich regions, as predicted by the Cr(x)Mo(1-x) phase diagram.


TLR agonists prevent the establishment of allogeneic hematopoietic chimerism in mice treated with costimulation blockade.
Activation of TLR4 by administration of LPS shortens the survival of skin allografts in mice treated with costimulation blockade through a CD8 T cell-dependent, MyD88-dependent, and type I IFN receptor-dependent pathway. The effect of TLR activation on the establishment of allogeneic hematopoietic chimerism in mice treated with costimulation blockade is not known. Using a costimulation blockade protocol based on a donor-specific transfusion (DST) and a short course of anti-CD154 mAb, we show that LPS administration at the time of DST matures host alloantigen-presenting dendritic cells, prevents the establishment of mixed allogeneic hematopoietic chimerism, and shortens survival of donor-specific skin allografts. LPS mediates its effects via a mechanism that involves both CD4(+) and CD8(+) T cells and results from signaling through either the MyD88 or the type I IFN receptor pathways. We also document that timing of LPS administration is critical, as injection of LPS 24 h before treatment with DST and anti-CD154 mAb does not prevent hematopoietic engraftment but administration the day after bone marrow transplantation does. We conclude that TLR4 activation prevents the induction of mixed allogeneic hematopoietic chimerism through type I IFN receptor and MyD88-dependent signaling, which leads to the up-regulation of costimulatory molecules on host APCs and the generation of alloreactive T cells. These data suggest that distinct but overlapping cellular and molecular mechanisms control the ability of TLR agonists to block tolerance induction to hematopoietic and skin allografts in mice treated with costimulation blockade.


Occidiofungin inhibition of Candida biofilm formation on silicone elastomer surface.
Candida are opportunistic fungal pathogens with medical relevance given their association with superficial to life-threatening infections. An important component of Candida virulence is the ability to form a biofilm. These structures are highly resistant to antifungal therapies and are often the cause of treatment failure. In this work, we evaluated the efficacy of the antifungal compound, occidiofungin, against Candida biofilms developed on a silicone surface. We demonstrate that occidiofungin eliminated cells at all stages of biofilm formation in a dose-dependent manner. Consistent with our understanding of occidiofungin bioactivity, we noted alterations to actin organization and cell morphology following antifungal exposure. Given the challenges associated with the treatment of biofilm-associated infections, occidiofungin exhibits potential as a therapeutic antifungal agent in the future.


Xrn1 influence on gene transcription results from the combination of general effects on elongating RNA pol II and gene-specific chromatin configuration.
mRNA homoeostasis is favoured by crosstalk between transcription and degradation machineries. Both the Ccr4-Not and the Xrn1-decaysome complexes have been described to influence transcription. While Ccr4-Not has been shown to directly stimulate transcription elongation, the information available on how Xrn1 influences transcription is scarce and contradictory. In this study we have addressed this issue by mapping RNA polymerase II (RNA pol II) at high resolution, using CRAC and BioGRO-seq techniques in Saccharomyces cerevisiae. We found significant effects of Xrn1 perturbation on RNA pol II profiles across the genome. RNA pol II profiles at 5' exhibited significant alterations that were compatible with decreased elongation rates in the absence of Xrn1. Nucleosome mapping detected altered chromatin configuration in the gene bodies. We also detected accumulation of RNA pol II shortly upstream of polyadenylation sites by CRAC, although not by BioGRO-seq, suggesting higher frequency of backtracking before pre-mRNA cleavage. This phenomenon was particularly linked to genes with poorly positioned nucleosomes at this position. Accumulation of RNA pol II at 3' was also detected in other mRNA decay mutants. According to these and other pieces of evidence, Xrn1 seems to influence transcription elongation at least in two ways: by directly favouring elongation rates and by a more general mechanism that connects mRNA decay to late elongation.


The crucial role of DNA-dependent protein kinase and myelin transcription factor 1-like protein in the miR-141 tumor suppressor network.
Glioblastoma is the most aggressive brain tumor. Although miR-141 has been demonstrated to primarily function as a tumor suppressor in numerous malignancies, including glioblastoma, the mechanisms involved remain poorly understood. Here, it is shown that miR-141 is downregulated in glioblastoma cell lines and tissues and may exert its biological function via directly targeting myelin transcription factor 1-like (MYT1L). Using two glioblastoma cell lines that differ from each other by the functionality of DNA-dependent protein kinase (DNAPK), a functional involvement of DNAPK in the miR-141 tumor suppression network was observed. In M059K cells with a normal function of DNAPK, the enforced expression of miR-141 attenuated MYT1L expression and suppressed cell proliferation. Conversely, the inhibition of miR-141 expression promoted cell proliferation; however, in M059J cells with a loss-of-function DNAPK, miR-141 constitutively inhibited cell proliferation upon ectopic overexpression or inhibition. An overexpression of miR-141 suppressed M059J cell migration, while it had no effect on M059K. Furthermore, the ectopic expression of miR-141 induced an S-phase arrest in both cell lines, whereas the inhibition of miR-141 caused a G1 arrest in M059J and accelerated the S phase in M059K. An overexpression and suppression of miR-141 resulted in an aberrant expression of cell-cycle proteins, including p21. Moreover, MYT1L may be a transcription factor of p21 in p53-mutant cells, whereas DNAPK may function as a repressor of MYT1L. The findings revealed the crucial role of DNAPK in miR-141-mediated suppression of gliomagenesis and demonstrated that it may be a target molecule in miR-141-associated therapeutic interventions for glioblastoma.


Consolidation therapy for childhood acute lymphoblastic leukaemia: clinical and cellular pharmacology of cytosine arabinoside, epipodophyllotoxins and cyclophosphamide.
The intensification of post-remission induction therapy has been shown to improve the relapse-free survival for childhood acute lymphoblastic leukaemia (ALL), and is now a standard component of the treatment of childhood acute lymphoblastic leukaemia. For cytosine arabinoside (ara-C), methotrexate, vincristine and corticosteroids, in-vitro studies indicate that the extracellular drug concentration and exposure time are important determinants of cytotoxicity for human leukaemia cell lines. For L-asparaginase, epipodopyllotoxins and cyclophosphamide, there have been few studies of the relationship between cellular pharmacology and cytotoxicity in relation to ALL. The clinical and cellular pharmacology of methotrexate and cytosine arabinoside have been studied in relation to childhood ALL in vivo. For these drugs, there is evidence to suggest that maintenance of plasma concentrations that are biochemically optimal is necessary to maximize anti-leukaemic effects. For cytosine arabinoside in particular, optimal extracellular fluid concentrations are not likely to be achieved or maintained by bolus or short-duration i.v. infusions. A potentially important example of this may be served by the success of antimetabolite-based intrathecal chemotherapy for CNS-directed treatment of childhood ALL. Intrathecal administration of both methotrexate and cytosine arabinoside results in prolonged leukaemic cell exposure to cytotoxic concentrations of the drug. For vincristine, anthracyclines and asparaginase, the actual dose intensity received by children during consolidation therapy may be important, and there is considerable interpatient variation in the pharmacokinetics of cyclophosphamide and teniposide in the therapy of childhood cancers. The importance of this relationship to childhood ALL is not known. The pharmacological and cellular pharmacological studies performed at St Jude Children's Research Hospital (Memphis, TN, USA) have allowed investigation of the relationships between the clinical and cellular pharmacology of methotrexate and prognosis, and have supported the individualization of consolidation therapy with this drug. Cytosine arabinoside has been less well studied in relation to childhood ALL, although evidence exists to suggest that the administration of conventional-dose bolus or infusion schedules may not be optimal in terms of the antileukaemic efficacy of this antimetabolite. For L-asparaginase, ongoing studies may allow the relationship between dose and schedule of administration to be related to pharmacodynamic measures such as asparagine depletion and prognosis. Therefore, through knowledge of clinical and cellular pharmacological properties, it may be possible to optimize the consolidation phase of therapy for childhood ALL, without disrupting the fundamental principles by which the overall treatment is administered. This may be particularly important for children with disease that has inherent or acquired resistance to therapy.


Mouse hematopoietic stem cells and the interaction of c-kit receptor and steel factor.
Hematopoietic stem cells (HSCs) are distinguished from other hematopoietic progenitors in bone marrow by their unique ability to undergo multilineage differentiation and self-renewal. Two mouse mutations, dominant spotting (W) and steel (Sl), have pleiotropic effects on hematopoiesis, gametogenesis, and melanoblast development. These two mutations have been shown to be intrinsic (W) and microenvironmental (Sl) defects. Recently, molecular studies revealed that the W and Sl loci encode the c-kit receptor and steel factor (SLF), respectively. The c-kit receptor is expressed on HSCs and hematopoietic progenitors, while SLF is produced by stromal cells. SLF acts on hematopoietic progenitors synergistically with other growth factors. Here we review the effect of these mutations on mouse hematopoiesis, and show that SLF acts on HSCs and other myeloerythroid progenitors, but that it, in our hands, does not play a critical role in HSC generation or self-renewal. Rather, SLF is the most potent co-mitogen (with IL-1, IL-3, IL-6, G-CSF, GM-CSF, or M-CSF) found that acts on these cells, but the effect of such treatments is the rather specific and massive expansion of myeloerythropoiesis, not lymphopoiesis, and perhaps at the expense of HSC self-renewal.


A rapid method for the isolation of L-cell surface membranes using an aqueous two-phase polymer system.
A dextran-polythylene glycol aqueous two-phase system has been used to separate cell surface membranes from other cellular organelles. The surface membranes have been identified on the basis of morphology, content of Na(+), K(+)-ATPase, and presence of surface antigen as detected by a(51)Cr release method. Contamination of the surface membrane preparations by smooth endoplasmic reticulum, mitochondria, and nuclei has been found to be minimal. An average of 6.5% of the total protein was found in the membrane fraction. Less than two hours is required to isolate the membrane fraction after preparation of a Dounce homogenate. Fractionation by aqueous two-phase polymer systems appears to be a rapid and effective method for the isolation of surface membranes.


Inhaled corticosteroids might not increase the risk of pneumonia in patients with chronic obstructive pulmonary disease in Japan.
The use of inhaled corticosteroid (ICS) in patients with chronic obstructive pulmonary disease (COPD) decreases the frequency of COPD exacerbations. Recently, pneumonia was reported as a complication of ICS in patients with COPD. However, there have been few reports concerning the relationship between ICS and pneumonia in Japan. Moreover, there is little information on the types of ICS. To clarify these issues, we investigated the occurrence of pneumonia in Japanese patients with COPD. We retrospectively investigated the occurrence of pneumonia in patients with COPD in our hospital from January 2009 to August 2013. Morbidity and mortality, ICS use, age, sex, and COPD classification were investigated. A group of patients with COPD who received ICS and a group of patients with COPD who did not receive ICS were compared each other. Fifty-one patients developed pneumonia among 639 (7.98%) patients with COPD. Among 252 ICS-treated patients with COPD, 13 (5.16%) developed pneumonia, and among 387 ICS-untreated patients with COPD, 38 (9.82%) developed pneumonia. The mortality rate in ICS-treated patients with COPD was 7.7%, while that in ICS-untreated patients was 10.5% (P=0.767). Fluticasone/salmeterol use tended to show a higher risk of pneumonia than budesonide/formoterol use. The use of ICS did not increase the risk of pneumonia or mortality due to pneumonia in Japanese patients with COPD. ICS might not increase the risk of pneumonia in Japanese patients with COPD. In regard to pneumonia, ICS can be safely used in Japanese patients with COPD. Because there are apparent differences in lung diseases among races, appropriate treatment should be investigated in each country.


Two of a Kind? Mapping the Psychopathological Space between Obesity with and without Binge Eating Disorder.
(1) Background: Obesity (OB) is a frequent co-morbidity in Binge Eating Disorder (BED), suggesting that both conditions share phenotypical features along a spectrum of eating-related behaviors. However, the evidence is inconsistent. This study aimed to comprehensively compare OB-BED patients against OB individuals without BED and healthy, normal-weight controls in general psychopathological features, eating-related phenotypes, and early life experiences. (2) Methods: OB-BED patients (n = 37), OB individuals (n = 50), and controls (n = 44) completed a battery of standardized questionnaires. Responses were analyzed using univariate comparisons and dimensionality reduction techniques (linear discriminant analysis, LDA). (3) Results: OB-BED patients showed the highest scores across assessments (e.g., depression, emotional and stress eating, food cravings, food addiction). OB-BED patients did not differ from OB individuals in terms of childhood traumatization or attachment styles. The LDA revealed a two-dimensional solution that distinguished controls from OB and OB-BED in terms of increasing problematic eating behaviors and attitudes, depression, and childhood adversities, as well as OB-BED from OB groups in terms of emotional eating tendencies and self-regulation impairments. (4) Conclusions: Findings support the idea of a shared spectrum of eating-related disorders but also highlight important distinctions relevant to identifying and treating BED in obese patients.


[Blood coagulation disorders observed in arteriosclerosis obliterans].
Activated platelet function indicated by beta-TG and PF4 is observed in the patients from arteriosclerosis obliterans (ASO) with severe disturbance of peripheral circulation. Increase in FpA, TAT, FDP and PIC suggest that blood coagulation and fibrinolysis are accelerated. Fibrinolysis might be activated in response to thrombus formation in screlotic peripheral artery. It is suggested that antiplatelet and/or anticoagulation therapy is acceptable for ASO with disorders of blood coagulation and fibrinolysis. Adequate antithrombotic therapy is necessary not only to treat ASO but also to prevent progression of arterioscrelosis. It is important to recognize harmful influence of antithrombotic therapy (antiplatelet, anticoagulation or thrombolysis) on blood coagulation and fibrinolysis, on the patient being canditate for vascular surgery.


Left bundle-branch block: the relationship between electrocardiogram electrical activation and echocardiography mechanical contraction.
The relationship between myocardial electrical activation by electrocardiogram (ECG) and mechanical contraction by echocardiography in left bundle-branch block (LBBB) has never been clearly demonstrated. New strict criteria for LBBB based on a fundamental understanding of physiology have recently been independently published for both ECG and echocardiography. The relationship between the 2 modalities and the relation to cardiac resynchronization therapy (CRT) response was investigated. Sixty-six patients with LBBB by conventional criteria had a standard 12-lead ECG and 2-dimensional strain echocardiography performed before CRT implantation. Criteria for LBBB by echocardiography included early termination of contraction in one wall and prestretch and late contraction in opposing wall(s). New strict criteria by ECG included QRS duration ≥140 ms (men) or 130 ms (women), QS or rS in leads V1 and V2, and mid-QRS notching or slurring in ≥2 of leads V1, V2, V5, V6, I, and aVL. Response was defined as >15% decrease in left ventricular end-systolic volume after 6 months. In 64 of 66 patients, ECG analysis was possible. Echo and ECG readings for LBBB presence were concordant in 54 (84%) of 64. Thirty-seven (82%) of 45 patients with LBBB by strict ECG criteria responded to CRT, whereas only 4 (21%) of the 19 patients without LBBB responded (sensitivity 90% and specificity 65%). Thirty-six (95%) of 38 patients with concordance for the presence of LBBB responded to CRT. In patients with concordance for the absence of LBBB, 15 (94%) of 16 did not respond. For the first time, a close relation has been demonstrated between electrical activation by ECG and mechanical contraction by echocardiography. These findings may help identify CRT candidates.


The associations of Leishmania major and Leishmania tropica aspects by focusing their morphological and molecular features on clinical appearances in Khuzestan Province, Iran.
Cutaneous leishmaniasis has various phenotypic aspects consisting of polymorphic amastigotes with different genetic ranges. Samples were collected from suspected patients of Khuzestan province. Prepared smears were stained, scaled, and measured using ocular micrometer. The Cyt b, ITS-rDNA, and microsatellite genes of Leishmania were amplified and Leishmania species were identified by molecular analyses. Of 150 examined suspected patients, 102 were identified to Leishmania species (90 L. major, nine L. tropica, and three unidentified). The amastigotes of 90 L. major had regular and different irregular shapes within three clinical lesions with no and/or low genetic diversity. Three haplotypes of Cyt b of L. major were found but no variation was observed using ITS-rDNA gene. Interesting findings were that all nine L. tropica had regular amastigote shapes with more genetic variations, also a patient which had coinfection of L. major, L. tropica, and Crithidia. At least two L. major and L. tropica were identified in suspected patients of the regions. Different irregular amastigotes' shapes of L. major can be explained by various reservoir hosts and vectors. In contrast, more molecular variations in L. tropica could be justified by genetic characters. Unidentified Leishmania could be mixed pathogens or nonpathogens with mammals' Leishmania or Crithidia.


Subphenotyping and Classification of Orofacial Clefts: Need for Orofacial Cleft Subphenotyping Calls for Revised Classification.
Nonsyndromic orofacial clefting (OFC) describes a range of phenotypes that represent the most common craniofacial birth defects in humans, with an overall birth prevalence of 1:700 live births. Because of the lifelong negative implications on health and well-being associated with OFC and the numbers of people affected, quality research into its etiology, diagnosis, treatment outcomes, and preventative strategies is essential. A range of different methods is used for recording and classifying OFC subphenotypes, one of which is the International Classification of Diseases (ICD) system. However, there is a general perception that research is being hampered by a lack of sensitivity and specificity in grouping those with OFC into subphenotypes, with potential heterogeneity and confounding in epidemiologic, genetic, and genotype-phenotype correlation studies. This article provides a background to the necessity of OFC research, discusses current controversies within cleft subphenotyping, and provides a brief overview of current OFC classifications as well as their limitations. The LAHSHAL classification is described in the context of a potentially useful tool for OFC that could complement the ICD-10/ICD-11 Beta coding systems to become a simply understood, universally accepted, clinically friendly, and research-sensitive instrument. Empowering registries, clinicians, and researchers to use a common classification system would have significant implications for OFC research across the world at a time when accurate subphenotyping is crucial and health care research is becoming increasingly tailored toward the individual.


[Aging and hypertension as factors of progressive renal failure].
This study evaluated the effects of aging on renal hemodynamic, biochemical and histological parameters in spontaneously hypertensive rats. Systolic blood pressure was measured in male SHR (adult--adSHR and aged--agSHR) during four weeks, indirectly, once a week At the end of the experiment 24 h urine samples were collected and hemodynamic measurements were performed. Animals were sacrificed and blood samples were collected for biochemical analysis. The left kidney was histopathologically examined. Our results show that there is no difference in systolic blood pressure between adult and aged SH rats. Renal blood flow was significantly decreased (0.68+/-0.08 vs. 0.99+/-0.007 ml/min/100 g b.w.), while renal vascular resistance increased by 28.90% in aged gSH rats. Plasma creatinine (Pcr) level was decreased in agSHR compared to adSHR (p<0.001). There was no difference in creatinine clearance, because urine volume was significantly increased in the aged rats (p<0.001). Protein excretion (Pex) and filtration fraction were significantly increased in aged rats compared to adult rats (Pex: p<0.001, and FF: p<0.05). The degree of focal-segmental glomerulosclerosis measured by a semiquantitative histological technique was significantly increased in the aged rats compared to adult. Sporadic focal tubular atrophy and dilatation with periodic acid-schiff positive material were present in the aged group. Also there were changes in structure of afferent arterioles and small vessels with myointimal proliferation and reduced lumen diameter. There were no changes in lumen diameter of large renal vessels. Histopathological score of adult rats showed only minimal changes in vessel structure. These results show that aging, and long-term high arterial blood pressure are risk factors associated with hemodynamic changes in renal arteries and kidney vessels, advancement of glomerulosclerosis and tubular injury, and therefore may contribute to progression of renal failure and eventually cause end stage renal disease.


Characterization and source identification of hydrocarbons in water samples using multiple analytical techniques.
This paper describes a case study in which multiple analytical techniques were used to identify and characterize trace petroleum-related hydrocarbons and other volatile organic compounds in groundwater samples collected in a bedrock aquifer exploited for drinking water purposes. The objective of the study was to confirm the presence of gasoline and other petroleum products or other volatile organic pollutants in those samples in order to assess the respective implication of each of the potentially responsible parties to the contamination of the aquifer. In addition, the degree of contamination at different depths in the aquifer was also of interest. The analytical techniques used for analyses of water samples included gas chromatography-mass spectrometry (GC-MS) and capillary GC with flame-ionization detection, solid-phase microextraction and headspace GC-MS techniques. Chemical characterization results revealed the following: (1) The hydrocarbons in sample A (near-surface groundwater, 0-5 m) were clearly of two types, one being gasoline and the other a heavy petroleum product. The significant distribution of five target petroleum-characteristic alkylkated polycyclic aromatic hydrocarbon homologues and biomarkers confirmed the presence of another heavy petroleum product. The concentrations of the TPHs (total petroleum hydrocarbons) and BTEX (collective name of benzene, toluene, ethylbenzene, and p-, m-, and o-xylenes) were determined to be 1070 and 155 microg/kg of water for sample A, respectively. (2) The deepest groundwater (sample B, collected at a depth ranging between 15 and 60 m) was also contaminated, but to a much lesser degree. The concentrations of the TPH and BTEX were determined to be only 130 and 2.6 microg/kg of water for sample B, respectively. (3) The presence of a variety of volatile chlorinated compounds to the groundwater was also clearly identified.


Identification of chlamydial T3SS inhibitors through virtual screening against T3SS ATPase.
Chlamydia trachomatis is a widespread sexually transmitted pathogen that resides within a special vacuole inside host cells. Although acute infection can be treated with antibiotics, chlamydia can enter persistent state, leading to chronic infection that is difficult to cure. Thus, novel anti-chlamydial compounds active against persistent chlamydia are required. Chlamydiae rely upon type III secretion system (T3SS) to inject effector proteins into host cell cytoplasm, and T3SS inhibitors are viewed as promising compounds for treatment of chlamydial infections. C. trachomatis ATPase SctN is an important T3SS component and has not been targeted before. We thus used virtual screening against homology modeled SctN structure to search for SctN inhibitors. Selected compounds were tested for their ability to inhibit chlamydial survival and development within eukaryotic cells, and for the ability to suppress normal T3SS functioning. We identified two compounds that were able to block normal protein translocation through T3SS and inhibit chlamydial survival within eukaryotic cells in 50-100 μm concentrations. These two novel T3SS inhibitors also possessed relatively low toxicity toward eukaryotic cells. A small series of derivatives was further synthesized for the most active of two inhibitors to probe SAR properties.


Effect of Perfluorinated Side-Chain Length on the Morphology, Hydrophobicity, and Stability of Xerogel Coatings.
Superhydrophobic surfaces can be quickly formed with supramolecular materials. Incorporating low-molecular-weight gelators (LMWGs) with perfluorinated chains generates xerogel coatings with low surface energies and high roughness. Here, we examine and compare the properties of the xerogel coatings formed with eight different LMWGs. These LMWGs all have a trans-1,2-diamidocyclohexane core and two perfluorinated ponytails, whose lengths vary from three to ten carbon atoms (CF3 to CF10). Investigation of the xerogels aims to provide in-depth information on the chain length effect. LMWGs with a higher degree of fluorination (CF7 to CF10) form superhydrophobic xerogel coatings with very low surface energies. Scanning electron microscopy images of the coatings show that the aggregates of CF5 and CF7 are fibrous, while the others are crystal-like. Aggregates of CF10 are particularly small and further assemble into a porous structure on the micrometer scale. To test their stabilities, the xerogel coatings were flushed multiple times with a standardized water flush test. The removal of material from the surface in these flushes was monitored by a combination of the water contact angle, contact angle hysteresis, and coating thickness measurements. A new method based on image processing techniques was developed to reliably determine the change of the coating thickness. The CF7, CF9, and CF10 surfaces show consistent hydrophobicity and coating durability after repetitive flushing tests. The length of the perfluorinated side chains thus has a significant effect on the morphology of the deposited xerogel coatings, their roughness, and, in consequence, their hydrophobicity and mechanical durability.


Potential of curcumin and resveratrol as biochemical and biophysical modulators during lung cancer in rats.
The present study explored chemopreventive aspects of curcumin and resveratrol in the experimental model of lung carcinogenesis in rats. The main aim was to establish efficacy of combined phytochemicals treatment over individual treatments in rat cancer model. The study was performed in terms of both biophysical and biochemical parameters. The rats were segregated into five groups, which included normal control, benzo[a]pyrene (BP) treated, BP + curcumin treated, BP + resveratrol treated, and BP + curcumin + resveratrol treated groups. The results confirmed significant changes in the biochemical indices of the BP treated rats. Further, radiorespirometric studies showed significant rise in the 14C-glucose turnover and uptakes in BP treated rats. Also, a significant increase in the cell proliferation was noticed indirectly by recording uptakes of 3H-thymidine in the lung slices of BP treated rats. On the other hand, supplementation with curcumin and resveratrol in combination to BP treated rats significantly modulated both biophysical and biochemical indices. The histopathological studies also supported the efficacy of combined treatment of phytochemicals during lung carcinogenesis. The present study concluded that the combination of curcumin and resveratrol efficiently modulated lung carcinogenesis in rats.


Seroprevalence of Anti-Toxoplasma gondii Antibodies Among Lebanese Pregnant Women.
Toxoplasma gondii, the causative agent of toxoplasmosis, is a zoonotic obligate intracellular protozoan parasite responsible for the infection of almost one-third of the world's population. T. gondii is particularly threatening for primo-infected pregnant women and may lead, following vertical transplacental transmission, to spontaneous abortion, miscarriage, or severe manifestations in the newborn. The aim of this study was to provide an updated estimate of the seroprevalence of anti-T. gondii antibodies among a group of Lebanese pregnant women and its seroconversion rate. This is a retrospective cohort study, in which medical records of 11,000 pregnant women were screened. These women visited a private Obstetrics and Gynecology clinic located in Beirut, the capital of Lebanon, during the period of January 1994 till September 2015. Serological results of anti-T. gondii immunoglobulin G (IgG) and immunoglobulin M (IgM) results of 2456 Lebanese pregnant women who fulfilled the inclusion criteria were included in the analysis. Seropositivity and seroconversion rates for women with repeated tests were reported according to age and area of residence. The overall anti-T. gondii IgG and IgM seropositivity among 2456 Lebanese pregnant women was 82.6% and 1.8% respectively. The highest IgG seropositivity is among the age group of 35-44 years (87.81%) and at the governorate of "Mount Lebanon" (82.95%). Sixty-four seroconversions were detected and two abortions due to T. gondii infection during pregnancy were recorded. The seroprevalence of anti-T. gondii IgG among the screened pregnant women in Lebanon is the highest in the Arab region. These results highlight the importance of running a national sample survey to estimate the real potential burden of this infection and its impact on maternal and fetal health.


Hot Hydrogen Atom Irradiation of Protonated/Deprotonated Peptide in an Ion Trap Facilitates Fragmentation through Heated Radical Formation.
Tandem mass spectrometry with fragmentation involving the reaction with hydrogen atoms is expected to be useful for the analysis of peptides and proteins. In general, hydrogen atoms preferentially react with odd-electron radicals. The attachment of hydrogen atoms to even-electron peptide ions is barely observed because of their low reaction rate. To date, only the methodology developed by our group has successfully induced the fragmentation of even-electron peptide ions by reacting with hydrogen atoms. In the present study, we focused on the temperature of the peptide ions and hydrogen atoms in an ion trap mass spectrometer to understand the mechanism of the corresponding reaction. Because the reaction between even-electron peptide ions and hydrogen atoms has a significant transition state barrier, the use of hot hydrogen atoms is required to initiate the reaction. The reaction contributes to increase the internal energy of the resultant peptide radicals because the heat of reaction and kinetic energy of the hydrogen atom are converted to the internal energy of the product. The resultant oxygen- and carbon-centered peptide radicals undergo radical-induced fragmentation with sub-picosecond and sub-millisecond time scales, respectively.


Reasons for Hospitalization of Psoriasis Patients: A Report From the National Inpatient Sample.
Background We used a large United States population-based database to analyze the reasons for hospitalization of psoriasis patients. Methods International Classification of Diseases, 10th revision (ICD-10) code was used to identify hospitalizations in National Inpatient Sample (NIS) 2017 with a principal or secondary diagnosis of psoriasis. The reasons for hospitalization were divided into 19 categories based on their principal discharge ICD-10 diagnosis code. We also ranked the five most common specific reasons for hospitalization of psoriasis patients. Results There were over 35 million discharges included in the 2017 NIS database. A total of 165215 hospitalizations had either a principal or secondary ICD 10 code for psoriasis. Based on ICD-10 code categories, the top five reasons for hospitalization in patients with history of psoriasis were: Cardiovascular (CV) (26605, 16.10%), rheumatologic (19555, 11.84%), digestive (18465, 11.18%), infection (16395, 9.92%), and respiratory (14865, 9.00%). Sepsis was the most common principal diagnosis of psoriasis hospitalizations. Conclusion CV diseases were the most common ICD category, and sepsis was the most common principal diagnosis for psoriasis hospitalization. Management of medical co-morbidities is important in reducing rates of hospitalization of psoriasis patients.


Efficient visible-light-driven photocatalytic degradation of nitrophenol by using graphene-encapsulated TiO₂ nanowires.
In this work, a new hybrid nanocatalyst, namely titanium dioxide (TiO2) composite nanowires, encapsulated with graphene (G) and palladium nanoparticles (Pd NPs) (designated as G-Pd@TiO2-CNWs), was prepared. In preparing the nanowires, a combination of electrospinning and hydrothermal approaches was employed. The visible-light-driven photocatalytic performance of G-Pd@TiO2-CNWs was investigated using the reduction of 4-nitrophenol (4-NP) as a model reaction. The results showed that G-Pd@TiO2-CNWs converted nearly 100% of 4-NP under visible light irradiation. The reaction kinetics of the photocatalytic reduction of 4-NP was studied by UV-vis spectrophotometry and the apparent rate constant was determined and compared with those for other supported TiO2 catalysts. Furthermore, the spent G-Pd@TiO2-CNWs could be recovered by simple centrifugation and reused. The work is expected to shed new light on the development of G-incorporated hybrid nanostructures for harvesting light energy and on the development of new photocatalysts for the removal of environmental pollutants.


Intraoperative imaging techniques in the treatment of brain tumors.
Despite significant advances in medical imaging techniques and their routine preoperative use, real-time intraoperative information regarding anatomy remains of indisputable importance to neurosurgeons. Intraoperative displacement of the brain tissue caused by surgical retraction or the resection cavity itself, as well as shift caused by cerebrospinal fluid leakage, may result in alteration of the surgical anatomy of the lesion and surrounding structures. Neurosurgical navigation methods are beneficial in providing accurate intraoperative information regarding the anatomy of the surgical field. Furthermore, interactive image guidance may decrease incision lengths, operating times, and postoperative morbidity. This review focuses on recent developments in neurosurgical navigational techniques that enable real-time anatomic visualization during brain tumor surgery.


Elevated levels of serum fatty acid synthase in patients with gastric carcinoma.
Gastric cancer is the second leading cause of cancer mortality in the world. It is important to develop biomarkers for detecting new cancers at an early stage and for treating them early during recurrence in order to guide optimal treatment. Fatty acid synthase (FAS) is highly expressed in numerous human cancers and thus could potentially serve as such a biomarker, but the potential utility of measuring FAS for detecting gastric cancer has not been previously investigated. The aim of the present study was to provide a preliminary assessment of serum FAS as a marker of gastric carcinoma. The study included 47 patients with gastric cancer and 150 healthy subjects. Blood samples were collected from each cancer patient prior to treatment. Serum FAS levels were measured by ELISA and compared across the two groups of patients. Significantly higher levels of serum FAS were found in the gastric cancer patients [95% confidence interval (CI), 30.37-52.46] compared with the healthy controls (95% CI, 1.331-2.131), with elevated levels even in patients with early-stage tumors. These results indicate that measuring serum FAS levels has strong potential to provide a biomarker for the detection of gastric cancer, with high sensitivity and specificity.


Diastereo- and enantioselective synthesis of organometallic bis(helicene)s by a combination of C-H activation and dynamic isomerization.
Homochiral and heterochiral cis-bis-cycloplatinated-[6]helicene derivatives 1b(1,2), as representative examples of platina[6]helicenes that share a common platinum center, have been prepared. A diastereo- and enantioselective synthesis, which combines CH activation and dynamic isomerization from heterochiral structure 1b(2) into homochiral structure 1b(1), is also described. Overall, this isomerization process results in the transfer of chiral information from one helicene moiety to the other one. The chiroptical properties of homochiral (P)- and (M)-1b(1) were greatly modified upon oxidation into their corresponding (P)- and (M)-diiodo-Pt(IV) complexes (5). The changes were also analyzed by performing theoretical calculations. C-H activation in the synthesis of organometallic helicenes is further demonstrated by the preparation of cis-bis-cycloplatinated-[8]helicene 1c.


Epidemiology of neurological manifestations in Sjögren's syndrome: data from the French ASSESS Cohort.
Neurological manifestations seem common in primary Sjögren's syndrome (pSS) but their reported prevalences vary. We investigated the prevalence and epidemiology of neurological manifestations in a French nationwide multicentre prospective cohort of patients with pSS, the Assessment of Systemic Signs and Evolution in Sjögren's syndrome (ASSESS) cohort. The ASSESS cohort, established in 2006, includes 395 patients fulfilling American-European Consensus Group criteria for pSS. Demographic and clinical data were compared between patient groups with and without neurological manifestations, and across patient groups with peripheral nervous system (PNS) manifestations, central nervous system (CNS) manifestations and no neurological manifestations. Data at inclusion were available for 392 patients, whose mean age was 58±12 years. Mean follow-up was 33.9 months. Neurological manifestations were present in 74/392 (18.9%) patients, including 63 (16%) with PNS manifestations and 14 (3.6%) with CNS manifestations. Prevalences were 9.2% for pure sensory neuropathy, 5.3% for sensorimotor neuropathy, 1.3% for cerebral vasculitis and 1.0% for myelitis. Neurological manifestations were associated with greater pSS activity as assessed using the ESSDAI (9.4±6.8 vs 4.3±4.8; p<0.001) and proportion of patients taking immunomodulatory/immunosuppressive drugs (32.4% (24/74) versus 13.8% (44/318), p=0003). New neurological symptoms were more common in patients with than without prior neurological manifestations (RR=3.918 (95% CI 1.91 to 8.05); p<0.001). Prevalences of peripheral and central neurological manifestations in pSS are about 15% and 5%, respectively. Neurological manifestations are associated with greater pSS activity. New neurological manifestations are more common in patients with prior neurological involvement.


Unsymmetrical Relaxation Paths of the Excited States in Cyanine Dyes Detected by Time-Resolved Fluorescence: Polymethinic and Polyenic Forms.
Novel applications of organic dyes and vast opportunities for their molecular tailoring keep the focus of the scientific community on the issues of symmetry breaking in the systems having different location of uncompensated charge, which has tremendous impact on photoluminescent properties of the dyes. In this article, we provide distinctive experimental evidence of three relaxation paths (one symmetrical and two unsymmetrical) of excited states by analysis of lifetime and spectra of time-resolved fluorescence at low temperature with strong support of quantum-chemical modeling. Importantly, the studied cyanine dye (astraphloxin) in aqueous solution has two different unsymmetrical relaxation paths of excited states in the polymethinic and donor-acceptor polyenic forms, where the last form strongly diminishes in less polar media. The experimental and computational results provide essential fundamental knowledge of molecular electronic relaxations substantially affected by matrix rigidity and polarity for design and photonic applications of elongated π-electronic systems.


A Review of Excisional Goniotomy Performed with the Kahook Dual Blade for Glaucoma Management.
To review the published literature describing clinical outcomes of excisional goniotomy using the Kahook Dual Blade (KDB) for the management of glaucoma. A family of less invasive glaucoma procedures-including excisional goniotomy with the KDB-has been developed to provide moderate reductions in intraocular pressure and/or medication burden in eyes with therapeutic needs that may not warrant the risks associated with more traditional procedures such as trabeculectomy and tube-shunt implantation. This review's goal is to synthesize the existing literature into a compendium of excisional goniotomy's indications, technique, efficacy and safety outcomes, and optimal place in glaucoma management. Excisional goniotomy with the KDB effectively lowers IOP and reduces the medication burden in eyes with POAG and other forms of glaucoma across the spectrum of both baseline IOP and disease severity. The procedure exhibits a safety profile that is on par with other angle-based surgical interventions and enhanced safety compared to filtration procedures. It can be performed by comprehensive ophthalmologists as well as glaucoma specialists. This procedure as a standalone operation delivers IOP reductions consistent with filtration surgery, and in combination with cataract surgery delivers both IOP and medication reductions at least as great as other minimally invasive procedures. Given the broad base of evidence supporting its use in a wide variety of clinical scenarios, excisional goniotomy with the KDB can play a meaningful role in the achievement of patient-specific glaucoma therapy goals. These aggregate findings support the efficacy and safety of excisional goniotomy with the KDB and clarify the patient profiles best suited for this procedure. Dorairaj S, Radcliffe NM, Grover DS, et al. A Review of Excisional Goniotomy Performed with the Kahook Dual Blade for Glaucoma Management. J Curr Glaucoma Pract 2022;16(1):59-64.


The human mycobiome in health and disease.
The mycobiome, referring primarily to the fungal biota in an environment, is an important component of the human microbiome. Despite its importance, it has remained understudied. New culture-independent approaches to determine microbial diversity, such as next-generation sequencing methods, are greatly broadening our view of fungal importance. An integrative analysis of current studies shows that different body sites harbor specific fungal populations, and that diverse mycobiome patterns are associated with various diseases. By interfacing with other biomes, as well as with the host, the mycobiome probably contributes to the progression of fungus-associated diseases and plays an important role in health and disease.


T-cell autoimmunity in the central nervous system.
Studies of myelin basic protein (MBP)-specific T lymphocytes have been extraordinarily informative for several distinct aspects of (neuro) immunology. They indicated for the first time that myelin directed central nervous system (CNS) inflammation is mediated by specific autoaggressive T cells. This provided a conceptual basis for understanding the pathogenesis of anti-myelin autoimmunity in general. We assume at present that human multiple sclerosis (MS) is also caused by myelin-specific autoaggressive T cells, and that these T cells create the inflammatory changes typical for the generation of a mature demyelinating plaque. Large scale demyelination seems, however, not to be caused by purely cellular mechanisms. Second, studies using MBP-specific T-cell lines have critically contributed to elucidating the immune status of the CNS. They showed that the CNS is not completely secluded from the circulating immune cells. Activated, though not resting lymphocytes can pass through the endothelial blood-brain barrier and migrate through the brain tissues. There, in the CNS, some glia components, microglia and astrocytes can be induced by T-cell cytokines to act as efficient antigen-presenting cells. Thus, the CNS is subject to immune surveillance, though to a specialized, adapted variant thereof. Finally, studies using MBP-specific T cells established for the first time the presence of potentially autoaggressive T cells within the normal immune repertoire. This implies counterregulatory regulation required to keep the autoreactive T cells in a safe state of rest. Most recently, the analysis of the intrathymic anti-MBP T-cell repertoire may change our views on the generation of myelin-specific self tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)


Recommendations to Address the Unique Clinical and Psychological Needs of Transgender Persons Living With Multiple Sclerosis.
People living with multiple sclerosis (MS) face challenges coping with chronic illnesses, and transgender (TGD) persons living with MS may experience additional unique challenges and barriers to care. Medical biases toward TGD people are widely reported, and best practices in TGD MS care have not been identified. A case report of a TGD person living with MS is reviewed that helped to identify and inform us regarding the unique aspects of their clinical and psychological care needs. We conducted a systematic review of the literature according to the standard methods in PubMed. The literature was reviewed and summarized for relevant topics related to the unique care needs of TGD persons living with MS, and proposed care recommendations were created. We used the aforementioned case to identify and inform the special care needs and subsequently describe proposed recommendations to achieve inclusive comprehensive care of TGD persons with MS. The importance of providing an inclusive environment, comprehensive care, mental health screening, domestic violence screening, and case coordination are highlighted with the goal of providing best practice recommendations for the comprehensive inclusive care of TGD persons living with MS. The lack of published guidance on the care of TGD persons living with MS and our informative case have led to the proposed recommendations for the care of TGD persons living with MS.