Adolescent risk substance use behavior, posttraumatic stress, depression, and resilience: Innovative considerations for disaster recovery.
Natural and technological disasters cause long-term psychological trauma and increase substance use in adults. It is unclear whether these problems also occur in children and whether trauma influences long-term psychological outcomes due to developmental stages at the time of trauma. One community of interest is located in southeastern Louisiana, where, as children, many locals were exposed to Hurricane Katrina in 2005 and the Deepwater Horizon Oil Spill in 2010. We hypothesized individuals exposed to these disasters in early childhood would exhibit higher rates of anxiety, depression, and alcohol use as adolescents than the general population. To test this, we developed a questionnaire with a focus on severity of disaster exposure, indicators of psychological resilience, and current levels of anxiety, depression, and alcohol use. This survey was administered to over 1000 adolescents in local high schools throughout southeastern Louisiana. Structural equation modeling was performed to test correlations and moderation effects. We found disaster exposure was positively associated with trauma-like symptoms and substance use and psychological resilience was negatively related to these outcomes. These findings demonstrate childhood disaster exposure has the potential to cause chronic psychological distress and predispose individuals to substance use later in life. They also suggest resilience may be protective for disaster survivors. Future studies should expand these concepts to other age groups and types of disasters. Whether resilience-focused psychotherapy may be beneficial in these populations is also a relevant topic for exploration.


Average potassium concentration of the human body as a function of age.
Potassium-40 measurements on 1590 males and females ranging in age from less than 1 year to 79 years show sex differences and age trends in the ratio of muscle mass to the mass of other body constituents. A difference first at approximately 12 years of age. While females show a continuous decrease in potassium concentration, males show a rapid increase between the ages of 14 and 16. During adult life both sexes show a persistent and parallel decrease, which may be related to physiologic aging.


Clinical characteristics and prognosis of hospitalized patients with congestive heart failure--a study in Fukuoka, Japan.
The clinical characteristics and prognosis of patients with congestive heart failure (CHF) have been described by a number of previous studies, but very little information is available on this issue in Japan. This study aimed to delineate the clinical characteristics and prognosis of Japanese patients hospitalized with CHF. Medical records were reviewed for 230 consecutive patients at 5 teaching hospitals in Fukuoka, Japan from January to December 1997 and the survival and hospital readmission were followed through December 1999 (mean follow-up, 2.4 years). The study population had a high mean age, contained a larger population of women especially in the older ages, and had a higher incidence of overt HF (48%) despite a relatively normal ejection fraction on echocardiography. Major causes of CHF were ischemic, valvular, and hypertensive heart diseases. The 1-year mortality rate was as low as 8.3% whereas rates of hospital readmission because of an exacerbation of CHF were as high as 40% during the follow-up period. Patients hospitalized with CHF in routine clinical practice in Japan have characteristics that differ from those in the population included in community-based studies or large clinical trials.


Ancient schwannoma of the conus medullaris.
Cystic spinal or ancient schwannoma is a rare form of intradural tumour especially in the conus medullaris region. Due to its indolent behavior and benign course, the diagnosis of schwannoma is always a challenge and the imaging findings can be misleading. Our patient presented with chronic mild sciatica pain without any other neurological symptom. MRI of the spine showed intradural tumour located at the conus medullaris region with nerves compression and was reported as ependymoma. L3-L5 laminectomy and total excision of tumour was performed without any neurological complication. We concluded that ancient schwannoma of the conus medullaris is a rare benign tumour that can present with minimal non-specific neurological symptom that lead to misdiagnosis. Radical tumour excision is safe with an excellent outcome.


Changes in the expression of syndecan-1 in the colorectal adenoma-carcinoma sequence.
Syndecan-1, a transmembrane heparan sulphate proteoglycan (HSPG), functions as a matrix receptor on the basal surface of epithelial cells. It also co-localizes with E-cadherin at the lateral cell surface where its function is uncertain. Tumour development in the large bowel is associated with loss of normal epithelial adhesion and altered patterns of expression of cell adhesion molecules, possibly including syndecan-1. To evaluate changes in syndecan-1 expression during the development of colorectal neoplasia, 59 adenomas and 20 carcinomas arising from adenomas were investigated by immunohistochemistry. The staining intensity and distribution of syndecan-1 and E-cadherin in sequential sections was examined, semi-quantified and compared. Staining of syndecan-1 and E-cadherin was uniform in normal colorectal epithelial cells, and located at the basolateral surface. No significant change was seen in either molecule in mildly or moderately dysplastic adenomas. A significant reduction in expression of both syndecan-1 and E-cadherin was seen in severely dysplastic epithelium as compared to moderate dysplasia (P = 0.001 and P = 0.004 respectively). Similarly, there was a significant reduction of both molecules in carcinomas compared with associated adenomas (syndecan-1 P = 0.00003; E-cadherin P = 0.002). In both cases the loss of syndecan-1 expression was more striking than that of E-cadherin. Previous in vitro studies have shown that epithelial cells made deficient in syndecan-1 cease to express E-cadherin, suggesting a causal association. Our results support these findings and indicate that disruption of cell-matrix adhesion is critical in colorectal carcinogenesis, probably preceding changes in the purely homotypic cell-cell adhesion mediated by E-cadherin.


IFNγ and CTLA-4 Drive Hepatic CD4 T-Cell Tolerance and Protection From Autoimmunity in Mice.
The liver has a distinct capacity to induce immune tolerance to hepatic antigens. Although liver tolerance can be advantageous for preventing autoimmune and inflammatory diseases, it also can be detrimental by preventing immune surveillance of infected or malignant cells. Here, we investigated the immune mechanisms that establish hepatic tolerance. Tolerance was investigated in C-reactive protein (CRP)-myelin basic protein (MBP) mice expressing the neuroantigen MBP in hepatocytes, providing profound resistance to MBP-induced neuroinflammation. Tolerance induction was studied after transfer of MBP-specific CD4 T cells into CRP-MBP mice, and tolerance mechanisms were tested using depleting or blocking antibodies. Although tolerant CRP-MBP mice display increased numbers of forkhead box P3+ regulatory T cells, we here found them not essential for the maintenance of hepatic tolerance. Instead, upon MBP recognition in the liver, MBP-specific T cells became activated to produce interferon (IFN)γ, which, in turn, induced local up-regulation of recruitment molecules, including Chemokine (C-X-C motif) ligand9 and its receptor C-X-C motif chemokine receptor3, facilitating endothelial translocation and redirection of MBP-specific T cells into the hepatic parenchyma. There, the translocated MBP-specific CD4 T cells partly converted into interleukin 10-producing type 1 regulatory T cells, and significantly up-regulated the expression of immune checkpoint molecules, notably cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Intriguingly, although liver tolerance was not affected by impairment of interleukin 10 signaling, concomitant blockade of IFNγ and CTLA-4 abrogated hepatic tolerance induction to MBP, resulting in neuroinflammatory autoimmune disease in these mice. IFNγ-mediated redirection of autoreactive CD4 T cells into the liver and up-regulation of checkpoint molecules, including CTLA-4, were essential for tolerance induction in the liver, hence representing a potential treatment target for boosting or preventing liver tolerance.


Postprandial stimulation of insulin release by glucose-dependent insulinotropic polypeptide (GIP). Effect of a specific glucose-dependent insulinotropic polypeptide receptor antagonist in the rat.
Glucose-dependent insulinotropic polypeptide (GIP) is a 42-amino acid peptide produced by K cells of the mammalian proximal small intestine and is a potent stimulant of insulin release in the presence of hyperglycemia. However, its relative physiological importance as a postprandial insulinotropic agent is unknown. Using LGIPR2 cells stably transfected with rat GIP receptor cDNA, GIP (1-42) stimulation of cyclic adenosine monophosphate (cAMP) production was inhibited in a concentration-dependent manner by GIP (7-30)-NH2. Competition binding assays using stably transfected L293 cells demonstrated an IC50 for GIP receptor binding of 7 nmol/liter for GIP (1-42) and 200 nmol/liter for GIP (7-30)-NH2, whereas glucagonlike peptide-1 (GLP-1) binding to its receptor on ++betaTC3 cells was minimally displaced by GIP (7-30)-NH2. In fasted anesthetized rats, GIP (1-42) stimulated insulin release in a concentration-dependent manner, an effect abolished by the concomitant intraperitoneal administration of GIP (7-30)-NH2 (100 nmol/ kg). In contrast, glucose-, GLP-1-, and arginine-stimulated insulin release were not affected by GIP (7-30)-NH2. In separate experiments, GIP (7-30)-NH2 (100 nmol/kg) reduced postprandial insulin release in conscious rats by 72%. It is concluded that GIP (7-30)-NH2 is a GIP-specific receptor antagonist and that GIP plays a dominant role in mediating postprandial insulin release.


Molecular mechanism of NR4A1/MDM2/P53 signaling pathway regulation inducing ferroptosis in renal tubular epithelial cells involved in the progression of renal ischemia-reperfusion injury.
Revealing the possible molecular mechanism of the NR4A1 (nuclear receptor subfamily 4 group A member 1)-MDM2 (MDM2 proto-oncogene)-P53 (tumor protein p53) signaling pathway that induces ferroptosis in renal tubular epithelial cells. Renal ischemia-reperfusion injury (RIRI) -related datasets were obtained from the GEO database. Differentially expressed genes in RIRI were analyzed using R language, intersected with RIRI-related genes in the GeneCard database, and retrieved from the literature to finally obtain differential ferroptosis-related genes. An in vitro cell model of RIRI was constructed using mouse renal cortical proximal tubule epithelial cells (mRTEC cells) treated with hypoxia-reoxygenation (H/R). Bioinformatic analysis showed that NR4A1 may be involved in RIRI through the induction of ferroptosis; in addition, we predicted through online databases that the downstream target gene of NR4A1, MDM2, could be targeted and regulated by ChIP and dual luciferase assays, and that NR4A1 could prevent MDM2 by inhibiting its NR4A1 was able to promote ferroptosis by inhibiting the ubiquitinated degradation of P53. NR4A1 expression was significantly increased in mRTEC cells in the hypoxia/reoxygenation model, and the expression of ferroptosis-related genes was increased in vitro experiments. NR4A1 reduces the ubiquitinated degradation of P53 by targeting the inhibition of MDM2 expression, thereby inducing ferroptosis and ultimately exacerbating RIRI by affecting the oxidative respiration process in mitochondria and producing oxidized lipids. This study presents a novel therapeutic approach for the clinical treatment of renal ischemia-reperfusion injury by developing drugs that inhibit NR4A1 to alleviate kidney damage caused by renal ischemia-reperfusion.


Prolonged mechanical ventilation is associated with pulmonary complications, increased length of stay, and unfavorable discharge destination among patients with subdural hematoma.
Although subdural hematoma (SDH) is common in neurocritical practice, little is known about SDH patients requiring prolonged mechanical ventilation (PMV). We aimed to determine predictors of PMV and its relationship with outcome in patients with SDH. SDH patients admitted to Rush University neurointensive care unit from January 2009 to March 2012 were reviewed. Duration of intubation, pulmonary complications, demographics, treatment, discharge disposition, and length of stay (LOS) were reviewed. PMV was defined as duration of intubation >4 days. Univariate and multivariate analyses were performed to identify predictors of PMV and association with outcome among survivors with SDH. Of the 288 survivors with SDH, the mean age was 68, and of them 179 were male. A total of 137 required surgical SDH evacuation. Pneumonia occurred in 26 patients. Forty-eight patients (17%) required intubation, with duration of intubation being 1 to 20 days (median 3.0). Factors independently associated with PMV included alcohol abuse (OR, 4.31; 95% CI, 1.36-13.67), admission GCS<15 (OR, 11; 95% CI, 2.36-51.52), and surgical evacuation (OR, 9.27; 95% CI, 1.93-44.54). PMV predicted pneumonia (OR, 5.85; 95% CI, 1.52-22.57), tracheostomy (OR, 26.67; 95% CI, 2.93-242.67), increased LOS, and unfavorable discharge destination (OR, 73.1; 95% CI, 14.03-380.69). PMV is associated with pulmonary complications, increased LOS, and unfavorable discharge destination in patients with SDH. Alcohol abuse, admission GCS, and surgical evacuation are associated with PMV among patients with SDH. Future studies should investigate the role of early tracheostomy in high-risk patients and impact on outcomes.


[Simultaneous determination of tryptophan, tyrosine and phenylalanine in injection by derivative fluorescent PLS method].
A new first-derivative fluorescent method by partial least squares (PLS) for the simultaneous determination of tryptophan, tyrosine and Phenylalanine was developed. The determination was carried out in KH2PO4-K2HPO4 buffer solution (pH = 7.4) and at the EX (excite) wavelength of 216.6 nm. The method has been applied to the determination of tryptophan, tyrosine and phenylalanine in compound amino acid injection, and the relative errors are within +/- 7.2%.


Use of Consensus Methodology to Determine Candidate Items for Systemic Lupus Erythematosus Classification Criteria.
Given the complexity and heterogeneity of systemic lupus erythematosus (SLE), high-performing classification criteria are critical to advancing research and clinical care. A collaborative effort by the European League Against Rheumatism and the American College of Rheumatology was undertaken to generate candidate criteria, and then to reduce them to a smaller set. The objective of the current study was to select a set of criteria that maximizes the likelihood of accurate classification of SLE, particularly early disease. An independent panel of international SLE experts and the SLE classification criteria steering committee (conducting SLE research in Canada, Mexico, United States, Austria, Germany, Greece, France, Italy, and Spain) ranked 43 candidate criteria. A consensus meeting using nominal group technique (NGT) was conducted to reduce the list of criteria for consideration. The expert panel NGT exercise reduced the candidate criteria for SLE classification from 43 to 21. The panel distinguished potential "entry criteria," which would be required for classification, from potential "additive criteria." Potential entry criteria were antinuclear antibody (ANA) ≥ 1:80 (HEp-2 immunofluorescence), and low C3 and/or low C4. The use of low complement as an entry criterion was considered potentially useful in cases with negative ANA. Potential additive criteria included lupus nephritis by renal biopsy, autoantibodies, cytopenias, acute and chronic cutaneous lupus, alopecia, arthritis, serositis, oral mucosal lesions, central nervous system manifestations, and fever. The NGT exercise resulted in 21 candidate SLE classification criteria. The next phases of SLE classification criteria development will require refinement of criteria definitions, evaluation of the ability to cluster criteria into domains, and evaluation of weighting of criteria.


Exercise training improves endothelial function in young prehypertensives.
Prehypertensives exhibit marked endothelial dysfunction, a risk factor for future cardiovascular morbidity and mortality. However, the ability of exercise to ameliorate endothelial dysfunction in prehypertensives is grossly underinvestigated. This prospective randomized and controlled study examined the separate effects of resistance and endurance training on conduit artery endothelial function in young prehypertensives. Forty-three unmedicated prehypertensive (systolic blood pressure [SBP]=120-139 mmHg; diastolic blood pressure [DBP]=80-89 mmHg) but otherwise healthy men and women and 15 normotensive matched time-controls (NMTC); n = 15) between 18 and 35 y of age met screening requirements and participated in the study. Prehypertensive subjects were randomly assigned to either a resistance exercise training (PHRT; n = 15), endurance exercise training (PHET; n = 13) or time-control group (PHTC; n = 15). The treatment groups performed exercise training three days per week for eight weeks. The control groups did not initiate exercise programs throughout the study. Flow mediated dilation (FMD) of the brachial artery, biomarkers of enodothelial function and peripheral blood pressure were evaluated before and after exercise intervention or time-matched control. PHRT and PHET reduced resting SBP (9.6 ± 3.6 and 11.9 ± 3.4 mmHg, respectively; P < 0.05) and DBP (8.0 ± 5.1 and 7.2 ± 3.4 mmHg, respectively; P < 0.05). Exercise training improved brachial artery FMD absolute diameter, percent dilation and normalized percent dilation by 30%, 34% and 19% for PHRT, P < 0.05; and by 54%, 63% and 75% for PHET, P < 0.05; respectively. PHRT and PHET increased plasma concentrations of 6-keto prostaglandin F1α (19% and 22%, respectively; P < 0.05), NO x (19% and 23%, respectively; P < 0.05), and reduced endothelin-1 by (16% and 24%, respectively; P < 0.01). This study provides novel evidence that resistance and endurance exercise separately have beneficial effects on resting peripheral blood pressure, brachial artery FMD and endothelial-derived vasoactive agents in young prehypertensives.


Diabetes alters the myocardial cAMP-protein kinase cascade system.
An isolated perfused working rat heart preparation was used to assess the effect of alloxan-induced diabetes on the cAMP cascade system. Diabetes did not alter basal cAMP, cGMP content, or protein kinase or phosphorylase activities, but depressed (50%) isoproterenol-induced changes in cAMP content and protein kinase activity ratios. In contrast, phosphorylase activation and increased left ventricular pressure (LVP) were unaltered by diabetes. The relationship between cAMP and protein kinase activation is linear in hearts from both normal and diabetic rats. Diabetes did not alter this relationship. The relationship between protein kinase and phosphorylase activation or increases in LVP is also linear. An increase in the slopes obtained with diabetic hearts (P less than 0.05) was observed, suggesting an increased gain in the amplification cascade to protein kinase. The in vivo administration of insulin diminished this response. Thus, diabetes alters the ability of heart to accumulate cAMP and alters the gain of the amplification cascade system subsequent to protein kinase activation. This second effect may indicate an unmasking of a parallel regulatory pathway and in the beta-adrenergic regulation of phosphorylase activity and LVP.


2001 annual report of the Korea Central Cancer Registry: based on registered data from 134 hospitals.
To estimate the number of cancer cases during 2001, in Korea, through a nationwide hospital based cancer registration by the Korea Central Cancer Registry (KCCR). One hundred and thirty four hospitals participated in the KCCR program in 2001. Cancer cases were coded and classified according to the International Classification of Diseases for Oncology 2(nd) edition (ICD-O-2). The software program "IARC Check" was used to evaluate the quality of the registered cancer cases. Of the 111,816 malignancies registered, 10,106 (9.0%) duplicated malignancies were excluded. Among the remaining 95,542 malignancies, 3,598 (3.8%) cases with carcinoma in situ (Morphology code/2) were separated. Finally, 91,944 malignancies were analyzed. Of the total 91,944 malignancies, 51,753 (56.3%) cases were males and 40,191 (43.7%) were females. More than one third of cases were from the elderly (65 years old and more). The six leading primary cancer sites, in the order of their relative frequency, were stomach (24.1%), followed by the lung (16.0%), the liver (16.0%), the colorectum (10.5%), the bladder (3.4%), and the prostate (2.8%) among males. In females, the breast (16.1%) was the common cancer site, followed by the stomach (15.3%), the colorectum (10.5%), the cervix uteri (10.1%), the thyroid gland (8.3%) and the lung (6.6%). With the continued increase in cancer cases, the total number of registered cancer cases in Korea continues to rapidly increase.


Transketolase Activity but not Thiamine Membrane Transport Change in Response to Hyperglycaemia and Kidney Dysfunction.
Pentose phosphate pathway (PPP) with key enzyme transketolase (TKT), represents a potentially 'protective' mechanism in hyperglycaemia. Diabetic kidney disease (DKD), a common complication of both type 1 and type 2 diabetes associated with significant morbidity and mortality, represents the most common cause of chronic kidney disease (CKD). We hypothesized that protective PPP action in diabetes and eventually even more severely in concomitant DKD might be compromised by limited intracellular availability of an active TKT cofactor thiamine diphosphate (TDP). Effect of hyperglycaemia on gene expression and protein levels of key PPP loci was studied in vitro using human cell lines relevant to diabetes (HUVEC and HRGEC) and (together with measurement of TKT activity, plasma thiamine and erythrocyte TDP concentration) in vivo in diabetic vs. non-diabetic subjects with comparable renal function (n=83 in total). Hyperglycaemia significantly decreased protein levels of RFC-1, THTR1, THTR2 and TKT (P<0.05) in vitro. Analysis of blood samples from CKD patients with and without diabetes and from controls did not reveal any difference in gene expression and protein levels of thiamine transporters while TKT activity and TDP in erythrocytes gradually increased with decreasing kidney function being highest in patients with CKD3-4 of both diabetic and non-diabetic aetiology. Hyperglycaemia and uremic serum mimicking CKD in diabetes did not affect TKT activity in vitro (P<0.05). Both in vitro and human experiments showed decrease or unchanged expression, respectively, of thiamine transporters induced by hyperglycaemia while TKT activity in parallel with intracellular TDP was increased in CKD patients with or without diabetes. Therefore, lack of adaptive increase of thiamine transmembrane transport allowing further increase of TKT activity might contribute to compromised PPP function in diabetes and CKD and to the development of glycotoxic injury.


Southern analysis of genomic alterations in gamma-ray-induced aprt- hamster cell mutants.
The role of genomic alterations in mutagenesis induced by ionizing radiation has been the subject of considerable speculation. By Southern blotting analysis we show here that 9 of 55 (approximately 1/6) gamma-ray-induced mutants at the adenine phosphoribosyl transferase (aprt) locus of Chinese hamster ovary (CHO) cells have a detectable genomic rearrangement. These fall into two classes: intragenic deletions and chromosomal rearrangements. In contrast, no major genomic alterations were detected among 67 spontaneous mutants, although two restriction site loss events were observed. Three gamma-ray-induced mutants were found to be intragenic deletions; all may have identical break-points. The remaining six gamma-ray-induced mutants demonstrating a genomic alteration appear to be the result of chromosomal rearrangements, possibly translocation or inversion events. None of the remaining gamma-ray-induced mutants showed any observable alteration in blotting pattern indicating a substantial role for point mutation in gamma-ray-induced mutagenesis at the aprt locus.


Induction of plasminogen activator by alkylating agents in a repair defective human glioblastoma cell strain.
Alkylating agents, mechlorethamine and N-methyl-N'-nitro-N-nitrosoguanidine, induce the production of plasminogen activator in U-87MG cells, an alkylation DNA repair deficient (Mer-) human glioblastoma strain. Enzyme induction was not observed, however, in U-178MG and SH-101 cells, alkylation repair proficient (Mer+) glioblastoma strains, or in HeLa cells, which reactivated and supported well the growth of alkylation damaged adenovirus 3. In the alkylation repair defective U-87MG strain, enhanced production of plasminogen activator occurred in a narrow concentration range of treatment with either alkylating agent, causing a 20 to 50% inhibition of [3H]thymidine incorporation. Maximum plasminogen activator induction was observed between 32 and 48 h after alkylation treatment and the levels of enzyme produced were 5 to 10 times those of untreated control levels. This alkylation dependent enzyme induction required protein synthesis for it did not occur in the presence of cycloheximide. It was hence concluded that plasminogen activator induction in alkylation repair deficient human cells is caused by unrepaired DNA damage and that it may represent an eukaryotic SOS-like function. In addition, plasminogen activator induction may be useful as a sensitive assay for the identification of alkylation repair defective human tumors for which the susceptibility to alkylation chemotherapy should be expected to increase.


pyQms enables universal and accurate quantification of mass spectrometry data.
Quantitative mass spectrometry (MS) is a key technique in many research areas (1), including proteomics, metabolomics, glycomics, and lipidomics. Because all of the corresponding molecules can be described by chemical formulas, universal quantification tools are highly desirable. Here, we present pyQms, an open-source software for accurate quantification of all types of molecules measurable by MS. pyQms uses isotope pattern matching that offers an accurate quality assessment of all quantifications and the ability to directly incorporate mass spectrometer accuracy. pyQms is, due to its universal design, applicable to every research field, labeling strategy, and acquisition technique. This opens ultimate flexibility for researchers to design experiments employing innovative and hitherto unexplored labeling strategies. Importantly, pyQms performs very well to accurately quantify partially labeled proteomes in large scale and high throughput, the most challenging task for a quantification algorithm.


Ionotropic glutamate receptors are expressed in GABAergic terminals in the rat superficial dorsal horn.
Ionotropic glutamate receptors (IGR), including NMDA, AMPA, and kainate receptors, are expressed in terminals with varied morphology in the superficial laminae (I-III) of the dorsal horn of the spinal cord. Some of these terminals can be identified as endings of primary afferents, whereas others establish symmetric synapses, suggesting that they may be gamma-aminobutyric acid (GABA)-ergic. In the present study, we used confocal and electron microscopy of double immunostaining for GAD65, a marker for GABAergic terminals, and for subunits of IGRs to test directly whether IGRs are expressed in GABAergic terminals in laminae I-III of the dorsal horn. Although colocalization is hard to detect with confocal microscopy, electron microscopy reveals a substantial number of terminals immunoreactive for GAD65 also stained for IGRs. Among all GAD65-immunoreactive terminals counted, 37% express the NMDA receptor subunit NR1; 28% are immunopositive using an antibody for the GluR2/4 subunits of the AMPA receptor; and 20-35% are immunopositive using antibodies for the kainate receptor subunits GluR5, GluR6/7, KA1, or KA2. Terminals immunoreactive for IGR subunits and GAD65 establish symmetric synapses onto dendrites and perikarya and can be presynaptic to primary afferent terminals within both type 1 and type 2 synaptic glomeruli. Activation of presynaptic IGR may reduce neurotransmitter release. As autoreceptors in terminals of Adelta and C afferent fibers in laminae I-III, presynaptic IGRs may play a role in inhibiting nociception. As heteroreceptors in GABAergic terminals in the same laminae, on the other hand, presynaptic IGRs may have an opposite role and even contribute to central sensitization and hyperalgesia.


Mutual impact of clinically translatable near-infrared dyes on photoacoustic image contrast and in vitro photodynamic therapy efficacy.
Photodynamic therapy (PDT), a spatially localized phototoxic therapy that involves irradiation of a photosensitizer (PS) with specific wavelengths of light, has shown exceptional promise in impacting cancer treatment outcomes, particularly oral cancer. To reduce PDT outcome variability, attempts toward image-guided personalized PDT are being pursued by monitoring PS uptake either via fluorescence or photoacoustic imaging (PAI), a nonionizing modality dependent on optical absorption properties of the tissue. PAI-guided PDT requires a near-infrared contrast agent for deep tissue imaging with minimal photobleaching effect. We evaluate the impact of PDT agent, benzoporphyrin derivative (BPD), on PAI agent indocyanine green (ICG) and vice versa, given that they have different optical absorption properties and singlet oxygen quantum yields for PDT. Specifically, we demonstrate in two oral squamous cell carcinoma lines (FaDu and SCC4) that ICG has minimal effect on BPD PDT efficacy when irradiated with either a continuous or pulsed laser. Furthermore, the impact of BPD on ICG photodegradation was monitored with PAI in tissue-mimicking phantoms. These studies inform us that the combination of BPD and ICG can be utilized for PAI-guided PDT. However, researchers need to consider the photodegradation effects of ICG in the presence of BPD when designing their drug delivery strategies for PAI-guided PDT.


Evaluation of nano-ZnOs as a novel Zn source for marine fish: importance of digestive physiology.
Waterborne nanotoxicology of zinc oxide nanoparticles (nano-ZnOs) has been extensively studied over the past decade, whereas their potential dietary toxicity and applications were seldom investigated. In the present study, we systematically investigated both short-term bioavailability and chronic effects of nano-ZnOs to two marine fish (marine medaka Oryzias melastigma and red drum Sciaenops ocellatus). At normal supplementary level (80 mg Zn/kg), red drum (with a stomach) had similar assimilation efficiencies of nano-ZnOs and ZnCl2. Correspondingly, in vitro digestion experiments showed the continuous dissolution of nano-ZnOs in acid environment. In contrast, nano-ZnOs were more bioavailable than ZnCl2 to medaka (stomach-less) at 80 mg Zn/kg supplementary level. There results were further validated by using bulk-ZnOs. Chronic dietary exposure to nano-ZnOs (80 mg/kg) significantly enhanced the antioxidative defenses in medaka, with no negative effect on fish growth. Beneficial effects disappeared in the high dietary nano-ZnOs (300 mg/kg) treatment. For the first time, we provided direct evidence that nano-ZnOs was more bioavailable than ZnCl2 and bulk-ZnOs to stomach-less fish at normal dietary Zn inclusion level (<80 mg/kg), with potential benefits on antioxidative defenses. It is also necessary to pay attention to the dietary nano-ZnOs toxicity on stomach-less fish due to the presence of real 'nano-effects.'


Kinetic and mechanical analysis of live tube morphogenesis.
Ribbon is a nuclear Broad Tramtrack Bric-a-brac (BTB) -domain protein required for morphogenesis of the salivary gland and trachea. We recently showed that ribbon mutants exhibit decreased Crumbs and Rab11-coincident apical vesicles and increased apical Moesin activity and microvillar structure during tube elongation. To learn how these molecular and morphological changes affect the dynamics of tubulogenesis, we optimized an advanced two-photon microscope to enable high-resolution live imaging of the salivary gland and trachea. Live imaging revealed that ribbon mutant tissues exhibit slowed and incomplete lumenal morphogenesis, consistent with previously described apical defects. Because Moesin activity correlates with cortical stiffness, we hypothesize that ribbon mutants suffer from increased apical stiffness during morphogenesis. We develop this hypothesis through mechanical analysis, using the advantages of live imaging to construct computational elastic and analytical viscoelastic models of tube elongation, which suggest that ribbon mutant tubes exhibit three- to fivefold increased apical stiffness and twofold increased effective apical viscosity.


The LSM 510 META - ConfoCor 2 system: an integrated imaging and spectroscopic platform for single-molecule detection.
Fluorescence Correlation Spectroscopy (FCS) has developed into a routine method to quantitatively study diffusion of molecules and kinetic processes. FCS has recently become popular to complement live cell imaging with biophysical information. The enabling technology has been commercially realised by combining laser scanning microscopes and fluorescence correlation spectrometers in one integrated platform. This article provides an overview of the Zeiss solution of such a combined instrument, the LSM 510 META / ConfoCor 2 system. We focus on the instrumental set up as well as technical advances and improvements in the software that controls FCS data acquisition and evaluation. In addition, we outline the calibration of the instrument and the work flow for data analysis with emphasis on in vivo pharmacological applications.


Racial and Ethnic Inequities in the Return-to-Work of Workers Experiencing Injury or Illness: A Systematic Review.
Non-White workers face more frequent, severe, and disabling occupational and non-occupational injuries and illnesses when compared to White workers. It is unclear whether the return-to-work (RTW) process following injury or illness differs according to race or ethnicity. To determine racial and ethnic differences in the RTW process of workers with an occupational or non-occupational injury or illness. A systematic review was conducted. Eight academic databases - Medline, Embase, PsycINFO, CINAHL, Sociological Abstracts, ASSIA, ABI Inform, and Econ lit - were searched. Titles/abstracts and full texts of articles were reviewed for eligibility; relevant articles were appraised for methodological quality. A best evidence synthesis was applied to determine key findings and generate recommendations based on an assessment of the quality, quantity, and consistency of evidence. 15,289 articles were identified from which 19 studies met eligibility criteria and were appraised as medium-to-high methodological quality. Fifteen studies focused on workers with a non-occupational injury or illness and only four focused on workers with an occupational injury or illness. There was strong evidence indicating that non-White and racial/ethnic minority workers were less likely to RTW following a non-occupational injury or illness when compared to White or racial/ethnic majority workers. Policy and programmatic attention should be directed towards addressing racism and discrimination faced by non-White and racial/ethnic minority workers in the RTW process. Our research also underscores the importance of enhancing the measurement and examination of race and ethnicity in the field of work disability management.


Quantum optimally controlled transition landscapes.
A large number of experimental studies and simulations show that it is surprisingly easy to find excellent quality control over broad classes of quantum systems. We now prove that for controllable quantum systems with no constraints placed on the controls, the only allowed extrema of the transition probability landscape correspond to perfect control or no control. Under these conditions, no suboptimal local extrema exist as traps that would impede the search for an optimal control. The identified landscape structure is universal for all controllable quantum systems of the same dimension when seeking to maximize the same transition probability, regardless of the detailed nature of the system Hamiltonian. The presence of weak control field noise or environmental decoherence is shown to preserve the general structure of the control landscape, but at lower resolution.


Motorcycle helmet use and the risk of head, neck, and fatal injury: Revisiting the Hurt Study.
Most studies find strong evidence that motorcycle helmets protect against injury, but a small number of controversial studies have reported a positive association between helmet use and neck injury. The most commonly cited paper is that of Goldstein (1986). Goldstein obtained and reanalyzed data from the Hurt Study, a prospective, on-scene investigation of 900 motorcycle collisions in the city of Los Angeles. The Goldstein results have been adopted by the anti-helmet community to justify resistance to compulsory motorcycle helmet use on the grounds that helmets may cause neck injuries due to their mass. In the current study, we replicated Goldstein's models to understand how he obtained his unexpected results, and we then applied modern statistical methods to estimate the association of motorcycle helmet use with head injury, fatal injury, and neck injury among collision-involved motorcyclists. We found Goldstein's analysis to be critically flawed due to improper data imputation, modeling of extremely sparse data, and misinterpretation of model coefficients. Our new analysis showed that motorcycle helmets were associated with markedly lower risk of head injury (RR 0.40, 95% CI 0.31-0.52) and fatal injury (RR 0.44, 95% CI 0.26-0.74) and with moderately lower but statistically significant risk of neck injury (RR 0.63, 95% CI 0.40-0.99), after controlling for multiple potential confounders.


[Oncologic risk factors in papillomavirus infection].
Cytological screening is essential for adequate diagnosis of gynecological cancer. Moreover, every effort should be made to identify such risks of cancer as viruses (HPV, Herpes simplex, cytomegalovirus, Epstein-Barr virus, etc.). When high risk HPV-16 and HPV-18 are detected, diagnostic strategies should include assay of blood prolactin and prolactin/TTH ratio. Virus-related tumors and various risk groups may be studied using HPV genotyping detection of high-risk alleles of certain genes. Hence, some HPV gene variants and gene polymorphism can be investigated as potential risk factors in women.


A new Ru complex capable of catalytically oxidizing water to molecular dioxygen.
We have prepared three new dinuclear ruthenium complexes having the formulas [Ru2II(bpp)(trpy)2(mu-L)]2+ (L = Cl, 1; L = AcO, 2) and [Ru2II(bpp)(trpy)2(H2O)2]3+ (3). The three complexes have been characterized through the usual spectroscopic and electrochemical techniques and, in the cases of 1 and 2, the X-ray crystal structures have been solved. In aqueous acidic solution, the acetato bridge of 2 is replaced by aqua ligands, generating the bis(aqua) complex 3 which, upon oxidation to its RuIVRuIV state, has been shown to catalytically oxidize water to molecular oxygen. The measured pseudo-first-order rate constant for the O2-evolving process is 1.4 x 10-2 s-1, more than 3 times larger than the higher one previously reported for Ru-O-Ru type catalysts. This new water-splitting catalyst also has improved stability with regard to any previously described, achieving a total of 18.6 metal cycles.


Measuring connectivity in linear multivariate processes: definitions, interpretation, and practical analysis.
This tutorial paper introduces a common framework for the evaluation of widely used frequency-domain measures of coupling (coherence, partial coherence) and causality (directed coherence, partial directed coherence) from the parametric representation of linear multivariate (MV) processes. After providing a comprehensive time-domain definition of the various forms of connectivity observed in MV processes, we particularize them to MV autoregressive (MVAR) processes and derive the corresponding frequency-domain measures. Then, we discuss the theoretical interpretation of these MVAR-based connectivity measures, showing that each of them reflects a specific time-domain connectivity definition and how this results in the description of peculiar aspects of the information transfer in MV processes. Furthermore, issues related to the practical utilization of these measures on real-time series are pointed out, including MVAR model estimation and significance assessment. Finally, limitations and pitfalls arising from model mis-specification are discussed, indicating possible solutions and providing practical recommendations for a safe computation of the connectivity measures. An example of estimation of the presented measures from multiple EEG signals recorded during a combined visuomotor task is also reported, showing how evaluation of coupling and causality in the frequency domain may help describing specific neurophysiological mechanisms.


LysR Family Regulator LttR Controls Production of Conjugated Linoleic Acid in Lactobacillus plantarum by Directly Activating the cla Operon.
Conjugated linoleic acids (CLAs) have attracted more attention as functional lipids due to their potential physiological activities, including anticancer, anti-inflammatory, anti-cardiovascular disease, and antidiabetes activities. Microbiological synthesis of CLA has become a compelling method due to its high isomer selectivity and convenient separation and purification processes. In Lactobacillus plantarum, the generation of CLA from linoleic acids (LAs) requires the combination of CLA oleate hydratase (CLA-HY), CLA short-chain dehydrogenase (CLA-DH), and CLA acetoacetate decarboxylase (CLA-DC), which are separately encoded by cla-hy, cla-dh, and cla-dc. However, the regulatory mechanisms of CLA synthesis remain unknown. In this study, we found that a LysR family transcriptional regulator, LTTR, directly bound to the promoter region of the cla operon and activated the transcription of cla-dh and cla-dc. The binding motif was also predicted by bioinformatics analysis and verified by electrophoretic mobility shift assays (EMSAs) and DNase I footprinting assays. The lttR overexpression strain showed a 5-fold increase in CLA production. Moreover, we uncovered that the transcription of lttR is activated by LA. These results indicate that LttR senses LA and promotes CLA production by activating the transcription of cla-dh and cla-dc. This study reveals a new regulatory mechanism in CLA biotransformation and provides a new potential metabolic engineering strategy to increase the yield of CLA.IMPORTANCE Our work has identified a novel transcriptional regulator, LTTR, that regulates the production of CLA by activating the transcription of cla-dh and cla-dc, essential genes participating in CLA synthesis in Lactobacillus plantarum This study provides insight into the regulatory mechanism of CLA synthesis and broadens our understanding of the synthesis and regulatory mechanisms of the biosynthesis of CLA.


Earmarked Taxes as a Policy Strategy to Increase Funding for Behavioral Health Services.
Earmarking taxes for behavioral health services is a policy strategy that many jurisdictions have implemented to increase funding for behavioral health systems. However, little has been written about these taxes, and limited guidance exists for policy makers who are pursing or implementing such taxes. This column summarizes approaches to designing earmarked behavioral health taxes, evidence of their impact, strategies to enhance implementation, and future directions for research. The column focuses on two jurisdictions: California, which imposes an additional 1% tax on all household income exceeding $1 million, and Washington State, which provides counties with the option of increasing sales tax by 0.1%.


Elective cesarean delivery at term and the long-term risk for endocrine and metabolic morbidity of the offspring.
Other than obesity, no definitive insights have been gained regarding the apparent association between mode of delivery and long-term endocrine and metabolic outcomes in the offspring. We aimed to determine whether elective cesarean delivery (CD) impacts on long-term endocrine and metabolic morbidity of the offspring. A population-based cohort analysis was performed including all singleton-term deliveries occurring between 1991 and 2014 at a single tertiary medical center. A comparison was performed between children delivered via a non-emergent CD and those delivered vaginally (VD). Hospitalizations of the offspring up to the age of 18 years involving endocrine morbidity were evaluated. A Kaplan-Meier survival curve was used to compare cumulative morbidity incidence. Cox and a Weibull regression models were used to control for confounders. During the study period 131,880 term deliveries met the inclusion criteria; 8.9% were elective non-urgent CDs (n=11,768) and 91.1% (n=120,112) were VDs. The survival curve demonstrated a significantly higher cumulative incidence of endo-metabolic morbidity in offspring born via CD (P=0.010). In the regression models, adjusted for maternal obesity, CD was not noted as an independent risk factor for long-term pediatric endocrine and metabolic morbidity of the offspring while maternal obesity emerged as a strong predictor. We therefore conclude that CD per-se does not appear to increase the risk for long-term pediatric endo-metabolic morbidity of the offspring.


Substrate interactions, effects of symmetry breaking, and convection in a 2D horizontally shaken granular system
We describe experiments on a horizontally shaken [x = Asin(omegat)] single layer of hard spheres rolling on a nearly horizontal surface. We identify a novel substrate-mediated convective flow which occurs when the system is tilted slightly so that the weak gravitational force, g-->(eff), acting on the particles is not parallel to the driving direction. As the shaking amplitude is increased, the system progresses through four regimes: solid-flat, solid-inclined, convective, and disordered. The control parameter is the driving velocity, Aomega, rather than the usual Aomega(2) of vertically shaken 3D systems. At the onset of convection, the critical velocity is V(c) approximately sqrt[2g(eff)d].


Multicenter Phase II trial of high-dose imatinib mesylate in metastatic melanoma: significant toxicity with no clinical efficacy.
Systemic treatment of metastatic melanoma is largely ineffective and alternative approaches are needed. Imatinib mesylate is an oral tyrosine kinase inhibitor that targets bcr-Abl, c-kit, platelet-derived growth factor receptor (PDGFR)-alpha, and PDGFR-beta, leading to remarkable clinical responses in several cancers. Signal transduction via c-kit, PDGFR-alpha, and PDGFR-beta has been demonstrated in malignant melanoma. The primary objective of this Phase II study was to determine the response rate, response duration, and the frequency of 6-month progression-free survival in patients who could receive up to 2 prior therapeutic regimens. Initially, patients received imatinib at at dose of 400 mg twice orally each day. Based on Simon's optimal design, the study allowed entry of 21 patients; if there were > or = 2 objective responses, accrual would then continue to a total of 41 patients. Twenty-six patients were enrolled. Patients experienced 29 episodes of Grade 3 and 2 episodes of Grade 4 toxicity (according to National Cancer Institute common toxicity criteria). No objective clinical responses were noted among the 25 evaluable patients. The median time to progression was 54 days and the median overall survival was 200 days. No patient was free of disease progression at 6 months. Paraffin-embedded tumor specimens from 15 patients were tested for expression of imatinib responsive kinases by immunohistochemistry. Three tumors had moderate and 5 tumors had weak staining for c-kit. Five tumor samples had weak staining for PDGFR-alpha and -beta. Imatinib is an inactive single agent in metastatic melanoma in a population of predominantely pretreated patients. The levels of c-kit and/or PDGFR-alpha, -beta expression in the current study were lower than previously reported. Alternative treatment strategies remain a priority for patients with advanced melanoma.


Ischemic stroke and fibrinogen in the elderly.
Senescence is accompanied by an important increase in prevalence and incidence of ischemic stroke. The plasma level of fibrinogen tends to increase with age in the elderly similarly to the prevalence of stroke. The aim of our study was to evaluate the age-related increase in fibrinogen plasma level in the elderly and to assess the presence of eventual differences between normal subjects and patients with previous ischemic stroke associated with precerebral atherosclerosis. Eighty inpatients (41 males and 39 females), consecutively admitted to our Geriatric Unit, were included to this study. The patient group was formed 32 subjects (20 males and 12 females) aged 50-79 years, suffering from cerebrovascular disease with one or several previous ischemic stroke episodes, having occurred at least 1 year earlier. The control group consisted of 48 normal subjects (21 males and 27 females) aged 50-79 years. Both control and patient groups were subdivided into three subgroups, according to their age: Group 1 (50-59 years), Group 2 (60-69 years)and Group 3 (70-79 years). The statistical comparison was carried out by means of the Mann-Whithney nonparametric test. In normal controls, a mild age effect is evident because only Group 3 shows fibrinogen levels significantly higher than those of Group 1. On the contrary, in patients with ischemic stroke, an age effect is already evident between Group 2 and Group 1; of course, also the comparison between patient Group 3 and Group I shows a statistically significant difference. Moreover, the levels of fibrinogen were significantly increased in patient Group 2 and 3 when compared to those of their respective age-matched controls. Our data are in agreement with those already available in the literature and demonstrate that fibrinogen in normal aging changes with age and shows a 19 %increase between age Group 1 and Group 3. Patients with ischemic stroke show an earlier and more evident age-related increase in fibrinogen than normal controls. Even if it is not possible to know, if the increase in fibrinogen is a consequence or not of the ischemic stroke, we can affirm that certainly the increased levels of fibrinogen should be considered as an important risk factor in the elderly for cerebrovascular disease and deserve treatment.


The Impact of Rehabilitation Frequencies in the First Year after Stroke on the Risk of Recurrent Stroke and Mortality.
Rehabilitation is essential for all poststroke patients to improve self-care ability. However, whether an increased frequency of rehabilitation reduces poststroke adverse events remains undetermined. We recruited 4899 patients with newly diagnosed ischemic stroke between January 1, 2000, and December 31, 2008, from our database and divided them into 3 groups according to their Charlson Comorbidity Index, and they were further categorized into 3 groups of different rehabilitation frequencies during their first year after stroke. Clinical adverse events including recurrent stroke, hip fracture, pneumonia, and all-cause mortality were analyzed by Cox regression analysis to investigate the protective effects of aggressive rehabilitation. We discovered that aggressive rehabilitation in the first year after stroke was significantly associated with a lower incidence of recurrent stroke and all-cause mortality despite the severity of patients' comorbidities. Further Cox regression analysis revealed decreased hazard ratios to develop recurrent stroke and all-cause mortality in patients with more intensive rehabilitation (P for trend <.05). However, no significant associations between rehabilitation frequency and pneumonia and hip fracture were identified in our study. Intensive rehabilitation during the first year after stroke should be recommended to prevent detrimental adverse events for stroke survivors.


The reality of patients requiring prolonged mechanical ventilation: a multicenter study.
The number of patients who require prolonged mechanical ventilation increased during the last decade, which generated a large population of chronically ill patients. This study established the incidence of prolonged mechanical ventilation in four intensive care units and reported different characteristics, hospital outcomes, and the impact of costs and services of prolonged mechanical ventilation patients (mechanical ventilation dependency ≥ 21 days) compared with non-prolonged mechanical ventilation patients (mechanical ventilation dependency < 21 days). This study was a multicenter cohort study of all patients who were admitted to four intensive care units. The main outcome measures were length of stay in the intensive care unit, hospital, complications during intensive care unit stay, and intensive care unit and hospital mortality. There were 5,287 admissions to the intensive care units during study period. Some of these patients (41.5%) needed ventilatory support (n = 2,197), and 218 of the patients met criteria for prolonged mechanical ventilation (9.9%). Some complications developed during intensive care unit stay, such as muscle weakness, pressure ulcers, bacterial nosocomial sepsis, candidemia, pulmonary embolism, and hyperactive delirium, were associated with a significantly higher risk of prolonged mechanical ventilation. Prolonged mechanical ventilation patients had a significant increase in intensive care unit mortality (absolute difference = 14.2%, p < 0.001) and hospital mortality (absolute difference = 19.1%, p < 0.001). The prolonged mechanical ventilation group spent more days in the hospital after intensive care unit discharge (26.9 ± 29.3 versus 10.3 ± 20.4 days, p < 0.001) with higher costs. The classification of chronically critically ill patients according to the definition of prolonged mechanical ventilation adopted by our study (mechanical ventilation dependency ≥ 21 days) identified patients with a high risk for complications during intensive care unit stay, longer intensive care unit and hospital stays, high death rates, and higher costs.


Adaptive differentiation of traits related to resource use in a desert annual along a resource gradient.
• Plant resource-use traits are generally hypothesized to be adaptively differentiated for populations distributed along resource gradients. Although nutrient limitations are expected to select for resource-conservative strategies, water limitations may select for either resource-conservative or -acquisitive strategies. We test whether population differentiation reflects local adaptation for traits associated with resource-use strategies in a desert annual (Helianthus anomalus) distributed along a gradient of positively covarying water and nutrient availability. • We compared quantitative trait variation (Q(ST)) with neutral genetic differentiation (F(ST)), in a common garden glasshouse study, for leaf economics spectrum (LES) and related traits: photosynthesis (A(mass), A(area)), leaf nitrogen (N(mass), N(area)), leaf lifetime (LL), leaf mass per area (LMA), leaf water content (LWC), water-use efficiency (WUE, estimated as δ(13)C) and days to first flower (DFF). • Q(ST)-F(ST) differences support adaptive differentiation for Amass , N(mass), N(area), LWC and DFF. The trait combinations associated with drier and lower fertility sites represent correlated trait evolution consistent with the more resource-acquisitive end of the LES. There was no evidence for adaptive differentiation for A(area), LMA and WUE. • These results demonstrate that hot dry environments can selectively favor correlated evolution of traits contributing to a resource-acquisitive and earlier reproduction 'escape' strategy, despite lower fertility.


Mung bean (Vigna radiata (L.)) coat extract modulates macrophage functions to enhance antigen presentation: A proteomic study.
The immunomodulatory effect of mung bean is mainly attributed to antioxidant properties of flavonoids; however, the precise machinery for biological effect on animal cells remains uncertain. To understand the physiological change produced by mung bean consumption, proteomic and metabolomic techniques were used. In vitro assay confirmed the importance of synergistic interaction among multiple flavonoids by IL-6 expression. Proteomic analysis detected that the abundance of 190 proteins was changed in lipopolysaccharide-stimulated RAW264.7 cells by treatment with coat extract. Pathway mapping revealed that a range of proteins were regulated including an interferon-responsive antiviral enzyme (2'-5'-oligoadenylate synthetase), antigen processing factors (immunoglobulin heavy chain-binding protein and protein disulfide-isomerase), and proteins related to proteasomal degradation. Major histocompatibility complex pathway was activated. These results suggest that mung bean consumption enhances immune response toward a Th2-promoting polarization. This study highlighted the immunomodulation of RAW264.7 cells in response to treatment with mung bean seed coat extract, using gel-free proteomic technique. The mechanism of immunomodulation by mung bean has not been described until today except for a report which identified HMGB1 suppression as a pathway underlying the protective effect against sepsis. This study suggested that the mung bean is involved in the regulation of antigen processing and presentation, and thus shifts immune response from acute febrile illness to specific/systemic and long-lasting immunity to protect the host.


[Fatty liver in pregnancy. A report of two cases and medical literature review].
Acute fatty liver of pregnancy is an uncommon and potentially fatal disorder usually found in the third trimester of pregnancy and the early days postpartum. It is characterized by a micro vesicular stheatosis of the liver, which is reversible with complete regression of the disease. We present two clinical cases, in the first one the patient developed encephalopathy and hypoglycemia in her third day post cesarean section; the patient underwent surgical exploration because of a subaponeurotic hematoma and the diagnosis was confirmed by liver biopsy. The patient presented spontaneous resolution of the disease and was discharged home on her 21st day after delivery. The second case was a patient on her 37th week of pregnancy that arrived to the emergency room complaining of malaise, nausea and vomit, her laboratory analyses were remarkable hypoglycemia and hyperbilirubinemia. She underwent elective pregnancy termination with a favorable maternal and fetal outcome towards spontaneous resolution. It is critical to diagnose and treat this disease in a expedite manner in order to have a favorable maternal and fetal outcome. The mortality rate has decreased dramatically from 80% in 1965 to 100% survival in 1999 according to the latest reviews. This regression of the symptoms and signs along with normalization of the laboratory values has driven some authors to call this disease as the "reversible peripartum liver failure".


Deploying Indocyanine Green Fluorescence-Guided Navigation System in Precise Laparoscopic Resection of Pediatric Hepatoblastoma.
Background: Hepatoblastoma (HB) is the most common form of liver cancer in children. To date, complete tumor resection is still the gold standard for treating HB. Indocyanine green (ICG) has been identified as a sensitive adjunct that is highly effective in the identification and surgical management of local and metastatic HB. It has thus becomes an increasingly popular choice among surgeons in HB resection surgeries that are fluorescence-guided. However, laparotomy remains the preferred choice in most cases since the applications and limitations of fluorescence-guided laparoscopic surgery in treating HB remain unclear. In this study, the characteristics and outcomes of laparoscopic HB resections that were guided by intraoperative ICG fluorescent imaging were investigated. Methods: Seven HB patients underwent ICG-guided laparoscopic HB resection surgery from August 2019 to December 2021. ICG was intravenously administered to the patients at a dosage of 0.5 mg/kg 48 h prior to the scheduled operation. During operation, tumor localization and resection boundary were guided by fluorescence visualization. The data on surgical and clinical features were collected retrospectively. Results: The resection area and tumor boundary could be clearly viewed in real-time under the ICG fluorescence imaging navigation system during operation, except for one patient who had received interventional chemoembolization before surgery. The image produced by laparoscopic fluorescence navigation was clear since it was not affected by ambient light. All tumors were completely resected as confirmed by negative margins for HB during postoperative pathological examination. No residual or recurrence were also found through computed tomography during follow-up visits from 9 to 37 months. Conclusions: ICG fluorescence-guided laparoscopic surgery is safe and effective in treating HB due to its ability to provide clear information on tumor localization and delineate tumor margins in real-time.


Clinical update on the use of mesenchymal stem cells in equine orthopaedics.
Stem cells have received much attention in recent times because of their potential to improve healing of othropaedic problems. This manuscript presents the genesis, issues and current state of stem cell treatment in equine medicine. Current literature supports the use of mesenchymal stem cells (MSCs) for treatment of orthopaedic problems.


The Ordre des médecins and the Jews in Vichy France, 1940-1944.
This paper examines the way in which the Jewish question was handled by the Ordre des Médecins, a representative institution for the medical profession created by the Vichy government. It discusses the historiography of Vichy anti-Semitism generally and goes on to analyze the background of anti-Semitism in the French medical profession in the 1930s, comparing it with anti-Semitism in other professions such as Law. The paper then discusses the reactions of the Ordre des Médecins and its governing body, the Conseil Supérieur, to the Vichy anti-Semitic legislation which affected the profession and compares its brand of anti-Semitism with the official Vichy policy. It focuses on the unequal battle between the Conseil Supérieur, whose members were typically traditional nationalistic and protectionist anti-Semites, and the Vichy government, where quasi-racial anti-Semitism was official policy. It explains the inevitable defeat of the Conseil Supérieur.


A new intrasurgical technique to safely and reproducibly induce partial unilateral urinary obstruction and renal scarring in a Rat Model.
Irreversible electroporation (IRE) uses microsecond-long electric pulses to kill cells through membrane permeabilization, without affecting surrounding extracellular structures. We evaluated whether IRE can be used to induce urinary obstruction for a rat model of renal scarring. Intrasurgical IRE (2000 V/cm, 90 pulses, 100 μs) with caliper electrodes was performed in the right proximal ureter in male rats (n = 24) which were euthanized at 2, 5, or 10 days post-treatment, following contrast-enhanced magnetic resonance imaging. Complete urinary tract (bilateral kidneys, ureter and bladder) was extracted, and scored on a five-point scale for renal dilation, ureteral dilation and hydronephrosis. Whole kidney sections underwent immunohistochemistry to quantify levels of macrophages (CD68), activated fibroblasts [α-smooth muscle actin (α-SMA)], collagen (Masson's Trichrome) and Hematoxylin and Eosin. Change in renal pelvis diameter and the number of glomeruli in the treated and contralateral urinary tract was also computed. Intrasurgical IRE performed with non-invasive caliper electrodes resulted in immediate loss of peristalsis in the treated ureteral segment, and cell death in the ureteral muscularis along with urothelial sloughing. Dilation of the ureter was observed on gross anatomic evaluation and histopathology. Magnetic resonance imaging indicated partial stricture and urinary obstruction in IRE-treated urinary tract, without evidence of urinoma, leakage or fistula formation. Enlargement of the kidney with progressive renal dilation and hydronephrosis was evident between Day 2 and Day 10 post-treatment. Obstructed kidney demonstrated scarring with elevated levels of tissue collagen, macrophages and α-SMA-positive fibroblasts. There was a steady decrease in the number of glomeruli in the obstructed kidney, while glomeruli numbers in the contralateral kidney remained unchanged through the 10-day observation period. IRE provides a safe and reproducible technique to induce partial ureteral obstruction and renal fibrosis in rat model without the need for ligation or its associated complications.


Gene expression profiling for the purposes of biomarker discovery in oral potentially malignant lesions: a systematic review.
Early and accurate diagnosis of oral potentially malignant lesions (OPML) is of critical importance in preventing malignant transformation. Although histopathological interpretation of the degree of epithelial dysplasia is considered the gold standard for diagnosis, this method is subjective and lacks sensitivity. Therefore, many attempts have been made to identify objective molecular biomarkers to improve diagnosis. Microarray technology has the advantage of screening the expression of the whole genome making it one of the best tools for searching for novel biomarkers. However, microarray studies of OPMLs are limited, and no review has been published to highlight and compare their findings. In this paper, we systematically review all studies that have incorporated microarray analyses in the investigation of gene profile alterations in OPMLs and suggest a set of commonly dysregulated genes across multiple gene expression profile studies. This list of common genes may help focus selection of markers for further analysis regarding their importance in the diagnosis and prognosis of OPMLs.


Enhanced Raman sensitivity and magnetic separation for urolithiasis detection using phosphonic acid-terminated Fe3O4 nanoclusters.
Surface-functionalized Fe3O4 nanoparticles are emerging as promising agents for the selective and magnetic separation of various biological molecules. In principle, by engineering the surface of Fe3O4 nanoparticles, they can be applied as tracers to seek and recognize metabolites and secretions of specific diseases. In this report, we developed Fe3O4 nanoclusters with high magnetization and an amino-functionalized surface via the reaction between FeCl2, a hydrazine reductant, and a gelatin polymer to demonstrate magnetically separated prevalent urinary crystals. The surface of the gelatin-coated Fe3O4 nanoclusters was modified by using aminopropylphosphonic acid by amine coupling using EDC and NHS, which led to the exposure of their phosphonic acid groups and improved their affinity for fine Ca-based urinary crystals in the patient's urine. By subjecting the Fe3O4 nanoclusters that were bound to urinary crystals to Raman spectroscopy analysis, the crystalline types of the pre-concentrated urinary components were easily identified. The assignment of the vibration peaks of the crystals is promising for eliminating the false positives that occur when using a microscopic analysis method for urine crystal diagnosis. Sample preparation and identification required less than 10 min. Finally, we demonstrated that this non-invasive analytic platform exhibits a rapid and efficient detection rate of single- and multi-component urinary crystals from urine metabolites. A good correlation (86%) was observed between this non-invasive analytic platform and the diagnostic reports from 35 urolithiasis patients. We expect that this Fe3O4 nanocluster integrated Raman spectrum method will provide crystal information that could help early management for urolithiasis patients.


Typing is writing: Linguistic properties modulate typing execution.
Typing is becoming our preferred way of writing. Perhaps because of the relative recency of this change, very few studies have investigated typing from a psycholinguistic perspective. In addition, and despite obvious similarities between typing and handwriting, typing research has remained rather disconnected from handwriting research. The current study aimed at bridging this gap by evaluating how typing is affected by a number of psycholinguistic variables defined at the word, syllable, and letter levels. In a writing-to-dictation task, we assessed typing performance by measuring response accuracy, onset latencies - an index of response preparation and initiation - and interkeystroke intervals (IKIs) - an index of response execution processes. The lexical and sublexical factors revealed a composite pattern of effects. Lexical frequency improved response latencies and accuracy, while bigram frequency speeded up IKIs. Sound-spelling consistency improved latencies, but had an inhibitory effect on IKI. IKIs were also longer at syllable boundaries. Together, our findings can be fit within a framework for typed production that combines the previously developed theories of spelling and typing execution. At their interface, we highlight the need for an intermediate hierarchical stage, perhaps in the form of a graphemic buffer for typing.


Anti-inflammatory activity of β-patchoulene isolated from patchouli oil in mice.
β-Patchoulene (β-PAE) is a tricyclic sesquiterpene isolated from the oil of Pogostemon cablin (patchouli oil), which has been widely used in traditional Chinese medicine for the treatment of inflammatory diseases. However, as one of the major principle of patchouli oil, the biological activity of β-PAE has not been explored so far. In the present study, the anti-inflammatory activity in vivo, and the underlying mechanism, of β-PAE was investigated on experimental mice models of acute inflammation, i.e. xylene-induced ear edema, acetic acid-induced vascular permeability and carrageenan-induced paw edema. The results showed that β-PAE evoked a significant dose-dependent inhibition of ear edema induced by xylene, paw edema induced by carrageenan and suppressed the increase of vascular permeability elicited by acetic acid. Histopathological analysis indicated that β-PAE could markedly decrease the cellular infiltration in paw tissue. β-PAE was also shown to significantly decrease the malondialdehyde (MDA) level and myeloperoxidase (MPO) activity in edema paw. In addition, carrageenan-induced production of some pro-inflammatory cytokines: tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), prostaglandin E2 (PGE2) and nitric oxide (NO), were suppressed in a dose-dependent manner in mice subjected to β-PAE pretreatment, and it also significantly down-regulated the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Further analysis revealed that β-PAE also inhibited the translocation of nuclear factor-κB (NF-κB) from the cytoplasm to the nucleus and stabilize the conversion of nuclear factor-κBα (IκBα) level. These results provided additional chemical and pharmacological basis for the traditional application of P. cablin in inflammatory disorders.


A bacteriophage capsid protein provides a general amyloid interaction motif (GAIM) that binds and remodels misfolded protein assemblies.
Misfolded protein aggregates, characterized by a canonical amyloid fold, play a central role in the pathobiology of neurodegenerative diseases. Agents that bind and sequester neurotoxic intermediates of amyloid assembly, inhibit the assembly or promote the destabilization of such protein aggregates are in clinical testing. Here, we show that the gene 3 protein (g3p) of filamentous bacteriophage mediates potent generic binding to the amyloid fold. We have characterized the amyloid binding and conformational remodeling activities using an array of techniques, including X-ray fiber diffraction and NMR. The mechanism for g3p binding with amyloid appears to reflect its physiological role during infection of Escherichia coli, which is dependent on temperature-sensitive interdomain unfolding and cis-trans prolyl isomerization of g3p. In addition, a natural receptor for g3p, TolA-C, competitively interferes with Aβ binding to g3p. NMR studies show that g3p binding to Aβ fibers is predominantly through middle and C-terminal residues of the Aβ subunit, indicating β strand-g3p interactions. A recombinant bivalent g3p molecule, an immunoglobulin Fc (Ig) fusion of the two N-terminal g3p domains, (1) potently binds Aβ fibers (fAβ) (KD=9.4nM); (2); blocks fAβ assembly (IC50~50nM) and (3) dissociates fAβ (EC50=40-100nM). The binding of g3p to misfolded protein assemblies is generic, and amyloid-targeted activities can be demonstrated using other misfolded protein systems. Taken together, our studies show that g3p(N1N2) acts as a general amyloid interaction motif.


Comparative analysis of the transcriptome across distant species.
The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters.


Provider perspectives of implementation of an evidence-based insomnia treatment in Veterans Affairs (VA) primary care: barriers, existing strategies, and future directions.
Cognitive behavioral therapy for insomnia (CBT-I) is a highly effective nonpharmacological intervention that is widely considered the gold standard for insomnia treatment. Insomnia is a prevalent and debilitating public health concern. Up to one third of the general population struggles with chronic insomnia, greatly increasing the risk for chronic pain and inflammation, depression and suicide, and cognitive decline. Over the last 10 years, the Veterans Health Administration (VHA) evidence-based psychotherapy training program has trained nearly 1000 providers to deliver CBT-I in hospitals and clinics nationwide. Despite increased access, most patients with insomnia receive sleeping medications instead of CBT-I. This is particularly concerning for vulnerable populations, like older adults, who may be at increased risk of harms from medications. The goal of this study was to obtain a broad range of perspectives on CBT-I implementation from providers who commonly utilize and deliver CBT-I. This work identifies barriers and successful strategies used to overcome these barriers to guide future implementation efforts promoting evidence-based sleep care. Semi-structured interviews, using the Consolidated Framework for Implementation Research (CFIR) as a guide, were conducted with 17 providers from five Veterans Affairs (VA) facilities (8 primary care physicians, 4 primary care psychologists, and 5 CBT-I coordinators). We used a thematic analysis approach in which common ideas were identified across interviews and then grouped into larger conceptual themes. Data were concurrently collected and analyzed with rapid assessment process (RAP) techniques. Findings suggested implementation barriers and facilitators related to the CFIR constructs of intervention characteristic (e.g., providers unfamiliar with primary evidence of CBT-I effectiveness), inner setting (e.g., sleep as a low relative priority in primary care), and outer setting (e.g., lack of external incentives for increasing CBT-I use), as well as several successful strategies, including use of local champions and supportive opinion leaders. These findings suggest promising opportunities to improve implementation of CBT-I, especially at facilities with less well-established CBT-I programs. Formal implementation trials are needed to systematically determine the real-world impact of strategies such as enlisting CBT-I champions, informing opinion leaders about CBT-I services, and promoting network weaving among primary care, mental health, and sleep clinics.


Heterologous expression and characterization of the manganese-oxidizing protein from Erythrobacter sp. strain SD21.
The manganese (Mn)-oxidizing protein (MopA) from Erythrobacter sp. strain SD21 is part of a unique enzymatic family that is capable of oxidizing soluble Mn(II). This enzyme contains two domains, an animal heme peroxidase domain, which contains the catalytic site, followed by a C-terminal calcium binding domain. Different from the bacterial Mn-oxidizing multicopper oxidase enzymes, little is known about MopA. To gain a better understanding of MopA and its role in Mn(II) oxidation, the 238-kDa full-length protein and a 105-kDa truncated protein containing only the animal heme peroxidase domain were cloned and heterologously expressed in Escherichia coli. Despite having sequence similarity to a peroxidase, hydrogen peroxide did not stimulate activity, nor was activity significantly decreased in the presence of catalase. Both pyrroloquinoline quinone (PQQ) and hemin increased Mn-oxidizing activity, and calcium was required. The Km for Mn(II) of the full-length protein in cell extract was similar to that of the natively expressed protein, but the Km value for the truncated protein in cell extract was approximately 6-fold higher than that of the full-length protein, suggesting that the calcium binding domain may aid in binding Mn(II). Characterization of the heterologously expressed MopA has provided additional insight into the mechanism of bacterial Mn(II) oxidation, which will aid in understanding the role of MopA and Mn oxidation in bioremediation and biogeochemical cycling.


Bilateral oculodermal melanocytosis.
A case of bilateral oculodermal melanocytosis is presented in a Negro man. It is suggested that the term "nervus of Ota" be superseded by the more accurate and descriptive terms of "dermal melanocytosis," "ocular melanocytosis," and "oculodermal melanocytosis."


Oral Microbiome and Nitric Oxide: the Missing Link in the Management of Blood Pressure.
Having high blood pressure puts you at risk for heart disease and stroke, which are leading causes of death in the USA and worldwide. One out of every three Americans has hypertension, and it is estimated that despite aggressive treatment with medications, only about half of those medicated have managed blood pressure. Recent discoveries of the oral microbiome that reduces inorganic nitrate to nitrite and nitric oxide provide a new therapeutic target for the management of hypertension. The presence or absence of select and specific bacteria may determine steady-state blood pressure levels. Eradication of oral bacteria through antiseptic mouthwash or overuse of antibiotics causes blood pressure to increase. Allowing recolonization of nitrate- and nitrite-reducing bacteria can normalize blood pressure. This review will provide evidence of the link between oral microbiota and the production of nitric oxide and regulation of systemic blood pressure. Management of systemic hypertension through maintenance of the oral microbiome is a completely new paradigm in cardiovascular medicine.


Recent advances in upstream process development for production of recombinant adeno-associated virus.
Recombinant adeno-associated virus (rAAV) is rapidly emerging as the preferred delivery vehicle for gene therapies, with promising advantages in safety and efficacy. Key challenges in systemic in-vivo rAAV gene therapy applications are the gap in production capabilities versus potential market demand and complex production process. This review summarizes current available information on rAAV upstream manufacturing processes and proposed optimizations for production. The advancements in rAAV production media were reviewed with proposals to speed up the cell culture process development. Furthermore, major methods for genetic element delivery to host cells were summarized with their advantages, limitations, and future directions for optimization. In addition, culture vessel selection criteria were listed based on production cell system, scale, and development stage. Process control at the production step was also outlined with an in-depth understanding of production kinetics and quality control.


Salpingitis due to Entamoeba histolytica.
We describe the pathology of a unique case of Fallopian tube amebiasis, associated with hydrosalpinx, in a 21-year-old woman. She complained of lower abdominal pain, had a foul-smelling green vaginal discharge and fever during one week. There was a discrete increase in body temperature and a painful abdominal palpation at the lower right side, with signs of local peritoneal irritation. Pathological examination showed a marked dilatation of the fallopian tube and hydrosalpinx. Microscopic examination showed a poorly formed granuloma composed of large macrophages with many Entamoeba histolytica trophozoites inside the fallopian tube. Even though it is a rare disease the correct diagnosis of female genital tract amebiasis is of great importance for the indication of proper therapy.


Autotransfusion of pleural fluid.
The 2050 Blood Recovery System is indicated for use as a water-seal chest drainage system to collect blood from the mediastinal or pleural cavity; when collected, this blood may be reinfused during surgery or immediately thereafter for palliation. In this case, autotransfusion was used to ease the patient's breathing. The reinfusion of high volumes of pleural fluid must be further evaluated in symptom management.


An international comparison of serum 25-hydroxyvitamin D measurements.
Vitamin D status is usually assessed by measuring the serum 25-hydroxyvitamin D (25(OH)D) concentration. This mainly depends on sunshine exposure, nutrition and age. Interlaboratory variation may hamper comparison between results from different populations. This study reports cross-calibration of the 25(OH)D assays of five laboratories. In study 1, serum 25(OH)D was measured with three different assays in 104 serum samples from a large vitamin D supplementation study. The mean serum 25(OH)D level was 80% higher when measured by competitive protein binding (CPB) assay than by high-performance liquid chromatography (HPLC), while radioimmunoassay (RIA) gave intermediate values. The highest correlation was observed between RIA and HPLC (r = 0.84, p <0.01). Of the serum 25(OH)D values in the lowest quartile by HPLC, 25% were not recognized by CPB and 21% were not recognized by RIA as belonging to the lowest quartile. In study 2, the five laboratories analyzed serum 25(OH)D in eight serum samples covering the concentration range very low to high, with five different assays. The differences between the mean values for serum 25(OH)D between the laboratories with the highest and lowest values was 38%. The ranking order of individual samples according to the serum 25(OH)D value was very similar in all laboratories. The results show that 25(OH)D values from different laboratories can not be assumed to be comparable unless a careful cross-calibration has been performed.


Molecular cloning, characterization and expression analysis of complement components in red sea bream (Pagrus major) after Edwardsiella tarda and red sea bream Iridovirus (RSIV) challenge.
The complement system plays an important role in immune regulation and acts as the first line of defense against any pathogenic attack. To comprehend the red sea bream (Pagrus major) immune response, three complement genes, namely, pmC1r, pmMASP and pmC3, belonging to the classical, lectin and alternative complement cascade, respectively, were identified and characterized. pmC1r, pmMASP, and pmC3 were comprised of 2535, 3352, and 5735 base mRNA which encodes 732, 1029 and 1677 aa putative proteins, respectively. Phylogenetically, all the three studied genes clustered with their corresponding homologous clade. Tissue distribution and cellular localization data demonstrated a very high prevalence of all the three genes in the liver. Both bacterial and viral infection resulted in significant transcriptional alterations in all three genes in the liver with respect to their vehicle control counterparts. Specifically, bacterial challenge affected the pmMASP and pmC3 expression, while the viral infection resulted in pmC1r and pmC3 mRNA activation. Altogether, our data demonstrate the ability of pmC1r, pmMASP and pmC3 in bringing about an immune response against any pathogenic encroachment, and thus activating, not only one, but all the three complement pathways, in red sea bream.


Experience of gratitude, awe and beauty in life among patients with multiple sclerosis and psychiatric disorders.
Feelings of gratitude and awe facilitate perceptions and cognitions that go beyond the focus of illness and include positive aspects of one's personal and interpersonal reality, even in the face of disease. We intended to measure feelings of gratitude, awe, and experiences of beauty in life among patients with multiple sclerosis and psychiatric disorders, particularly with respect to their engagement in specific spiritual/religious practices and their life satisfaction. We conducted a cross-sectional survey with standardized questionnaires to measure engagement in various spiritual practices (SpREUK-P) and their relation to experiences of Gratitude, Awe and Beauty in Life and life satisfaction (BMLSS-10). In total, 461 individuals (41 ± 13 years; 68% women) with multiple sclerosis (46%) and depressive (22%) or other psychiatric disorders (32%) participated. Among participants, 23% never, 43% rarely, 24% often, and 10% frequently experienced Gratitude. In contrast, 41% never, 37% rarely, 17% often, and 6% frequently experienced Awe. Beauty in Life was never experienced by 8% of the sample, and 28% rarely, 46% often, and 18% frequently experienced it. Gratitude (F = 9.2; p = .003) and Beauty in Life (F = 6.0; p = .015) were experienced significantly more often by women than men. However, the experience of Awe did not differ between women and men (F = 2.2; n.s.). In contrast to our hypothesis, Gratitude/Awe cannot explain any relevant variance in patients' life satisfaction (R2 = .04). Regression analyses (R2 = .42) revealed that Gratitude/Awe can be predicted best by a person's engagement in religious practices, followed by other forms of spiritual practices and life satisfaction. Female gender was a weak predictor and underlying disease showed no effect. Gratitude/Awe could be regarded as a life orientation towards noticing and appreciating the positive in life--despite the symptoms of disease. Positive spirituality/religiosity seems to be a source of gratitude and appreciation in life, whereas patients with neither spiritual nor religious sentiments (R-S-) seem to have a lower awareness for these feelings.


Use of the Internet and Mobile Phones for Self-Management of Severe Mental Health Problems: Qualitative Study of Staff Views.
Researchers are currently investigating the feasibility, acceptability, and efficacy of digital health interventions for people who experience severe mental health problems such as psychosis and bipolar disorder. Although the acceptability of digital health interventions for severe mental health problems appears to be relatively high and some people report successfully using the Internet and mobile phones to manage their mental health, the attitudes of mental health care staff toward such approaches have yet to be considered. The aim of this study was to explore mental health care staff experiences of clients with severe mental health problems engaging with the Internet and mobile phones to self-manage their mental health and their views toward these behaviors. The study also sought to examine the opinions expressed by mental health care staff toward digital health interventions for severe mental health problems to identify potential facilitators and barriers to implementation. Four focus groups were conducted with 20 staff working in mental health care services in the North West of the England using a topic guide. Focus groups involved 12 staff working in secondary care psychological services (7 participants in focus group 1 and 5 participants in focus group 4), 4 staff working in a rehabilitation unit (focus group 2), and 4 staff working in a community mental health team (focus group 3). Focus groups were transcribed verbatim, and transcripts were analyzed thematically to identify key themes that emerged from the data. Four overarching themes, two with associated subthemes, were identified: (1) staff have conflicting views about the pros and cons of using Web-based resources and digital health interventions to manage mental health; (2) digital health interventions could increase access to mental health support options for severe mental health problems but may perpetuate the digital divide; (3) digital health interventions' impact on staff roles and responsibilities; and (4) digital health interventions should be used to enhance, not replace, face-to-face support. This study is the first, to our knowledge, to qualitatively explore the experiences and attitudes of mental health care staff toward individuals with severe mental health problems using the Internet, mobile phones, and digital health interventions to self-manage their mental health. Understanding the positive and negative experiences and views shared by staff toward both current and potential digital health intervention use has enabled the identification of several considerations for implementation. Additionally, the findings suggest mental health care staff need clear guidance and training in relation to their responsibilities in recommending reputable and secure websites, forums, and digital health interventions and in how to manage professional boundaries on the Internet. Overall, the study highlights that digital health interventions could be well received by staff working in mental health services but importantly, such management options must be presented to frontline staff as an avenue to enhance care and extend choice, rather than as a method to reduce costs.


Abciximab, eptifibatide, and tirofiban exhibit dose-dependent potencies to dissolve platelet aggregates.
Platelet GPIIb/IIIa antagonists are not only used to prevent platelet aggregation, but also in combination with thrombolytic agents for the treatment of coronary thrombi. Recent data indicate a potential of abciximab alone to dissolve thrombi in vivo. We investigated the potential of abciximab, eptifibatide, and tirofiban to dissolve platelet aggregates in vitro. Adenosine diphosphate (ADP)-induced platelet aggregation could be reversed in a concentration-dependent manner by all three GPIIb/IIIa antagonists when added after the aggregation curve reached half-maximal aggregation. The concentrations chosen are comparable with in vivo plasma concentrations in clinical applications. Disaggregation reached a maximum degree of 72.4% using 0.5 microg/ml tirofiban, 91.5% using 3.75 microg/ml eptifibatide, and 48.4% using 50 microg/ml abciximab (P < 0.05, respectively). A potential fibrinolytic activity of the GPIIb/IIIa antagonists was ruled out by preincubation with aprotinin or by a plasma clot assay. A stable model Chinese hamster ovary (CHO) cell line expressing the activated form of GPIIb/IIIa was used to confirm the disaggregation capacity of GPIIb/IIIa antagonists found in platelets. Not only abciximab, but also eptifibatide and tirofiban have the potential to disaggregate newly formed platelet clusters in vitro. Because enzyme-dependent fibrinolysis does not appear to be involved, competitive removal of fibrinogen by the receptor antagonists is the most likely mechanism.


Superconductivity-induced optical anomaly in an iron arsenide.
One of the central tenets of conventional theories of superconductivity, including most models proposed for the recently discovered iron-pnictide superconductors, is the notion that only electronic excitations with energies comparable to the superconducting energy gap are affected by the transition. Here, we report the results of a comprehensive spectroscopic ellipsometry study of a high-quality crystal of superconducting Ba₀.₆₈K₀.₃₂Fe₂As₂ that challenges this notion. We observe a superconductivity-induced suppression of an absorption band at an energy of 2.5 eV, two orders of magnitude above the superconducting gap energy 2Δ≈20 meV. On the basis of density functional calculations, this band can be assigned to transitions from As-p to Fe-d orbitals crossing the Fermi level. We identify a related effect at the spin-density wave transition in parent compounds of the 122 family. This suggests that As-p states deep below the Fermi level contribute to the formation of the superconducting and spin-density wave states in the iron arsenides.


Unexpected complexity in the haplotypes of commonly used inbred strains of laboratory mice.
Investigation of sequence variation in common inbred mouse strains has revealed a segmented pattern in which regions of high and low variant density are intermixed. Furthermore, it has been suggested that allelic strain distribution patterns also occur in well defined blocks and consequently could be used to map quantitative trait loci (QTL) in comparisons between inbred strains. We report a detailed analysis of polymorphism distribution in multiple inbred mouse strains over a 4.8-megabase region containing a QTL influencing anxiety. Our analysis indicates that it is only partly true that the genomes of inbred strains exist as a patchwork of segments of sequence identity and difference. We show that the definition of haplotype blocks is not robust and that methods for QTL mapping may fail if they assume a simple block-like structure.


Psychological predictors of pain during dental hygiene treatment.
This study examined the role of catastrophizing (i.e. a tendency to exaggerate the threat value of potentially painful situations) in predicting pain experience during dental hygiene treatment. Participants in the research were 100 patients undergoing scaling and/or root planing procedures at Dalhousie University's Dental Clinic. Following treatment, participants completed the Pain Catastrophizing Scale, a measure of emotional distress, a pain scale, and the Dental Anxiety Scale-Revised. Participants who scored above the median on the Pain Catastrophizing Scale were classified as catastrophizers, participants who scored below the median were classified as noncatastrophizers. Results showed that catastrophizers reported significantly more dental anxiety, emotional distress and pain than noncatastrophizers; and that distress reactions were more pronounced in men that in women. Discussion focuses on the importance of addressing psychological factors in dental hygiene practice, particularly as they relate to reactions to dental hygiene procedures, and avoidance of dental care.


Cognitive impairment in multiple sclerosis: An exploratory analysis of environmental and lifestyle risk factors.
Many potentially modifiable risk factors for MS are investigated. It is not known, however, if these factors also apply to MS-related cognitive impairment (CI), a frequent consequence of MS. The aim of our study was to assess risk factors for CI in MS patients, focusing on environmental exposures, lifestyle and comorbidities. We included MS patients referring to MS Centers in Florence and Barletta between 2014 and 2017. Neuropsychological performance was assessed through the Rao's battery and Stroop test, cognitive reserve (premorbid intelligence quotient-IQ) was evaluated using the National Adult Reading Test (NART). Potential risk factors were investigated through a semi-structured questionnaire. 150 patients were included. CI was detected in 45 (30%) subjects and was associated with older age (p<0.005), older age at MS onset (p = 0.016), higher EDSS score (p<0.005), progressive disease course (p = 0.048) and lower premorbid IQ score (p<0.005). As for risk factors, CI was related with lower physical activity in childhood-adolescence (p<0.005). In women, hormonal therapy resulted to be protective against CI (p = 0.041). However, in the multivariable analysis, the only significant predictors of CI were older age (p<0.05; OR 1.06, 95% CI 1.02-1.10) and lower premorbid IQ (p<0.05; OR 0.93, 95% CI: 0.88-0.98). Removing IQ from the model, CI was associated with higher EDSS (p = 0.030; OR 1.25, 95% CI 1.02-1.53) and, marginally, previous physical activity (p = 0.066; OR 0.49, 95% CI: 0.23-1.05). Our findings suggest that physical activity in childhood-adolescence could be a contributor to cognitive reserve building, thus representing a potential protective factors for MS-related CI susceptible to preventive strategies.