Specific marker of feigned memory impairment: The activation of left superior frontal gyrus.
Faking memory impairment means normal people complain lots of memory problems without organic damage in forensic assessments. Using alternative forced-choice paradigm, containing digital or autobiographical information, previous neuroimaging studies have indicated that faking memory impairment could cause the activation in the prefrontal and parietal regions, and might involve a fronto-parietal-subcortical circuit. However, it is still unclear whether different memory types have influence on faking or not. Since different memory types, such as long-term memory (LTM) and short-term memory (STM), were found supported by different brain areas, we hypothesized that feigned STM or LTM impairment had distinct neural activation mapping. Besides that, some common neural correlates may act as the general characteristic of feigned memory impairment. To verify this hypothesis, the functional magnetic resonance imaging (fMRI) combined with an alternative word forced-choice paradigm were used in this study. A total of 10 right-handed participants, in this study, had to perform both STW and LTM tasks respectively under answering correctly, answering randomly and feigned memory impairment conditions. Our results indicated that the activation of the left superior frontal gyrus and the left medial frontal gyrus was associated with feigned LTM impairment, whereas the left superior frontal gyrus, the left precuneus and the right anterior cingulate cortex (ACC) were highly activated while feigning STM impairment. Furthermore, an overlapping was found in the left superior frontal gyrus, and it suggested that the activity of the left superior frontal gyrus might be acting as a specific marker of feigned memory impairment.


Economic evaluation of mental health care interventions. A review.
Due to rising costs, the economic aspects of the mental health care sector are receiving increasing attention. This article scrutinizes 91 published studies in the field of mental health care, applying methodological criteria drawn from epidemiology and economics. The purpose of this study is to provide some insight into the quality of economic evaluation in the field of mental health care. The article shows that few good full economic evaluations studies have been undertaken in the domain of mental health care. One reason for this could be that the measurement of effectiveness in mental health care is complicated because of the known difficulties with the reliability of psychiatric diagnosis and the lack of consensus about the etiology and appropriate treatment for many psychiatric illnesses.


Regulation and control of AP-1 binding activity in embryotoxicity.
The electrophoretic mobility shift assay (EMSA) is a sensitive relatively straightforward methodology used to detect sequence-specific DNA-protein interactions. It is the fundamental procedure of several variants that allow qualitative and quantitative assessments of protein-nucleic acid complexes. Classically, nuclear proteins and DNA are combined and the resulting mixture is electrophoretically separated in polyacrylamide or agarose gel under native conditions. The distribution within the gel is generally detected with autoradiography of the ³²P-labeled DNA. The underlying principle is that nucleic acid with protein bound to it will migrate more slowly through a gel matrix than the free nucleic acid. In this chapter, a representative protocol is described that addresses specific challenges of using whole embryos as the nuclear protein source, and the most common and informative EMSA variant, the "supershift," is also presented. The important points are underscored and approaches for troubleshooting are explained. References are provided for alternative methods and extensions of the basic protocol.


Stimulation through intercellular adhesion molecule-1 provides a second signal for T cell activation.
Regulation of T cell activation requires two signals. First, appropriately presented Ag in the context of MHC interacts with the T cell Ag receptor-CD3 complex. The best-studied second signal is CD28, which resides on the T cell and responds to its counter receptor, B7. A second signal also can be delivered through LFA-1 residing on the T cell, responding to its counter receptor ICAM-1 residing on a different cell. Characterization of a second signal is tied to its ability to costimulate (along with stimulation through the TCR) proliferation, IL-2 secretion, and coactivation of phosphatidylinositol 3-kinase. We examined whether ICAM-1, residing on the T cell surface, could deliver a second signal into that T cell. Costimulation through CD3 plus ICAM-1 caused increased T cell proliferation, increased expression of the activation marker CD69, increased transcription through the IL-2 regulatory region, and increased secretion of selected Th1 but not Th2 cytokines. Costimulation through CD3 plus ICAM-1 caused synergistic activation of phosphatidylinositol 3-kinase. Finally, the combination of anti-CD3 plus anti-ICAM-1 (but not anti-CD3 alone) caused prolonged proliferation of naive T cells in a manner similar to costimulation through LFA-1 or CD28. Thus, we demonstrate for the first time that ICAM-1 resident on a T cell can deliver a costimulatory signal into that T cell.


Dealloying assisted high-yield growth of surfactant-free <110> highly active Cu-doped CeO2 nanowires for low-temperature CO oxidation.
CeO2 is widely used as a commercial CO oxidation catalyst, but it suffers from high-temperature (>200 °C) complete conversion. Despite enormous efforts made to promote its low-temperature activity by interfacing CuO and CeO2, it is still a long-standing challenge to balance the desired catalytic activity with high-yield preparation. Creating intimate synergistic interfaces between Cu and Ce species and exploring surfactant-free large-scale methods are both critical and challenging. To address these concerns, we synthesized highly active Cu doped CeO2 nanowires for low-temperature CO oxidation, relying on intentionally maneuvering precursor alloy compositions and a high-yield dealloying method. The favorable one-dimensional doping structure inherited from the nanowire bundles of the as-dealloyed precursors, clean surfaces and intimate synergistic effects between Cu and Ce contribute to excellent CO oxidation performances, with 5% room-temperature conversion triggered at 35 °C and 100% conversion at 100 °C. 96% of O2 selectivity at 88 °C in CO preferential oxidation was also obtained. The long-term durability for 24 hours at 100% CO conversion without any decay confirms the robust characteristics of the catalysts. Moreover, this work offers some insights into the reasonable design of alloy precursors to realize property-oriented alloys to nanowires batch transformation for the study of industrial catalysts.


Damage maps of veneered zirconia under simulated mastication.
Zirconia-based restorations often fracture from chipping and/or delamination of the porcelain veneers. We hypothesized that veneer chipping/delamination is a result of the propagation of near-contact-induced partial cone cracks on the occlusal surface under mastication. Masticatory loading involves the opposing tooth sliding along the cuspal inner incline surface with an applied biting force. To test this hypothesis, we cemented flat porcelain-veneered zirconia plates onto dental composites and cyclically loaded them (contact-slide-liftoff) at an inclination angle as a simplified model of zirconia-based restorations under occlusion. In light of in situ observation of damage evolution in a transparent glass/zirconia/polycarbonate trilayer, post mortem damage evaluation of porcelain/zirconia/composite trilayers by a sectioning technique revealed that deep-penetrating occlusal surface partial cone fracture is the predominant fracture mode of porcelain veneers. Clinical relevance is discussed.


Effect of polycythemia on vascular volume in the newborn dog.
The effect of polycythemia [hematocrit (Hct) 64-80] on blood volume (BV) was studied in 27 unanesthetized, splenectomized newborn dogs (age 6-14 days, postsplenectomy 5-13 days). Normovolemic polycythemia (N) was induced in nine pups by exchange transfusion with 75 ml/kg of adult, packed (to Hct 95) red blood cells (RBC). Hypervolemic polycythemia (H) was induced in 11 pups by transfusion of RBC (50 ml/kg). Seven pups received exchange transfusion with 75 ml/kg of whole blood and served as controls (C). Red cell volume (RCV, 51CrRBC) and plasma volume (PV, 125I-fibrinogen and Evans blue) were measured prior to and at 1, 2, and 4 h after transfusion, before the pups received fluid orally. The pups were fed 8 ml X kg-1 X h-1 after 4 h, and measurements were repeated at 8 and 24 h. BV fell in C prior to 4 h by 10 +/- 4% (SD) (P less than 0.01) and then rose to initial levels. BV rose in the N pups by 17 +/- 9 (P less than 0.01), 14 +/- 5 (P less than 0.01), 9 +/- 10 (P less than 0.1), 17 +/- 9 (P less than 0.01), and 31 +/- 17% (P less than 0.01) at 1, 2, 4, 8, and 24 h post transfusion. BV rose in the H pups by 41 +/- 8, 35 +/- 10, 23 +/- 11, 27 +/- 6, and 43 +/- 9% (all P less than 0.01). Thus newborn dogs with induced N or H equilibrate rapidly to a BV significantly higher than C levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Optic disc hemorrhage may be associated with retinal nerve fiber loss in otherwise normal eyes.
To evaluate quantitatively the structural damage of the peripapillary retinal nerve fiber layer (RNFL) in eyes with disc hemorrhage (DH). Prospective cross-sectional study. Seventy patients with DH (70 eyes; mean age +/- standard deviation, 60.0+/-11.8 years) and 100 healthy control subjects (100 eyes; mean age +/- standard deviation, 57.7+/-8.0 years) were enrolled from the Glaucoma Clinic of Seoul National University Hospital. Normal eyes without DH (group 1: normal control group) served as controls. Eyes with DH were divided into the following groups: (1) eyes with a DH, accompanied by no visible RNFL defect according to red-free fundus photography and normal visual fields (group 2: DH only group); (2) eyes with a DH and a localized RNFL defect in the same quadrant, accompanied by normal visual fields (group 3: DH-preperimetric group); and (3) eyes with a DH and a localized RNFL defect in the same quadrant, accompanied by glaucomatous visual field defect in the corresponding hemifield location (group 4: DH-perimetric group). Optical coherence tomography (OCT)-measured RNFL thicknesses were compared. Average and segmental (4 quadrants and 12 clock-hours) OCT-measured RNFL thicknesses. The number of eyes in groups 1, 2, 3, and 4 was 100, 25, 22, and 23 eyes, respectively. The OCT-measured RNFL thickness was significantly different among the 4 groups in average RNFL thickness and in inferior, superior, and nasal quadrants (P<0.01, 1-way analysis of variance). On post hoc analysis, the eyes of groups 2 and 3 showed thinner average RNFL thickness than those of group 1, and the average RNFL thickness of group 4 was significantly lower than that of groups 2 and 3 (P<0.001, 1-way analysis of variance and Tukey's test). The OCT-measured RNFL thickness revealed a topographic relationship with the DH location. Significant RNFL loss was already present in the DH only eyes with apparently normal RNFL configuration by red-free fundus photography, indicating that preperimetric changes of the RNFL are already present. These results suggest that OCT has the potential to detect subclinical or preperimetric RNFL loss in the eyes with DH. The authors have no proprietary or commercial interest in any of the materials discussed in this article.


Effects of temporal variation in community-level fruit abundance on seed dispersal by birds across woody species.
In animal-dispersed plants, seed dispersal patterns of the same species in the same habitat can greatly differ among individuals and temporally. Many studies have revealed the pervasive effects of spatial variation in fruit abundance on seed dispersal of individual plants. By contrast, very few studies have investigated the temporal variation in seed dispersal. We investigated the effects of conspecific and community-level fruit abundance on fruit removal rate and seed dispersal distance of six bird-dispersed woody species in a Japanese temperate forest for 3 yr. The six species share similar fruit characteristics but have different fruiting seasons. In addition, we also considered the effects of bird seasonality in diet and species composition on seed dispersal. Inter-annual and inter-seasonal variation in community-level fruit abundance determined both fruit removal and the seed dispersal distance across species, but the effect differed with seasonal changes in bird behavior. Abundant fruit satiated fruit removal by birds only during fruit-feeding periods, not during insect-feeding periods. A scarcity of fruit increased the dispersal distance, but only during the migratory period. This difference was probably due to the different foraging behaviors of passing migrants and territorial birds. Our results illustrated that temporal variation in community-level fruit abundance could be a determining factor for seed dispersal in temperate forests. The effects of temporal variations in fruit abundance on seed dispersal patterns should be investigated in other ecosystems in order to understand their importance and associations with frugivore phenology.


Use of a locking intramedullary nail for the treatment of initial varus proximal humeral fracture: a prospective pilot study.
To evaluate the feasibility of locked intramedullary nailing, rather than locking plate fixation combined with fibular allograft augmentation, for initial varus proximal humeral fractures. This prospective pilot study enrolled patients with initial varus proximal humeral fractures that were treated with a locking intramedullary nail. Radiography was performed to evaluate fracture healing. Data about the visual analogue scale (VAS) pain score, Constant Shoulder Score (CSS), Disabilities of the Arm, Shoulder and Hand (DASH) score, American Shoulder and Elbow Surgeons (ASES) score and shoulder range of motion (ROM) were recorded. Twenty patients, including eight with Neer two-part and 12 with three-part fractures, were followed-up, with a mean time of 12.3 months. All patients sustained fractures that healed without re-varus. During the last follow-up, the shoulder function of the patients had recovered well, with a mean VAS pain score of 1.4, a mean CSS of 83.1, a mean DASH score of 80.8, a mean ASES score of 84.0 and a satisfactory ROM. In one patient, the proximal locking screw came out and was removed via a second surgery. The use of a locking intramedullary nail alone for initial varus proximal humeral two-/three-part fractures was feasible. This treatment has advantages, such as preventing re-varus and causing milder surgical trauma, than that seen with a locking plate.


The diagnostic value of beta-human chorionic gonadotropin, progesterone, CA125 in the prediction of abortions.
This study was conducted to investigate the effectiveness of serum levels of free beta-hCG, progesterone, CA125 and their combined use in the prediction of first trimester abortions. A total of 140 singleton pregnant women between 5 and 13 weeks' gestational age were included as Group I (n = 21) who resulted in abortion including missed abortion, incomplete abortion, complete abortion and inevitable abortion; Group II (n = 129) included normal pregnancies. When using the free beta-hCG level of <20 ng/ml as a cut off point, the sensitivity, specificity, PPV and NPV were 91%, 82%, 46% and 98%, when using a progesterone of <15 ng/ml as a cut off point, they were 91%, 89%, 59%, 98%. The single measurement of free beta-hCG or progesterone levels can be useful in the prediction of first trimester spontaneous abortions, but using progesterone may be recommended since it has high availability and low cost.


Analysis of Thomson scattered light from an arc plasma jet.
In this paper we present an analysis of Thomson scattered light from an arc plasma jet. Our approach goes beyond the standard random-phase approximation (RPA) and provides more consistent data for the electron temperature and density in plasmas that are weakly nonideal and collisional. The theory is based on a memory function formalism for the spectral density function with the use of the three lowest-order frequency-moment sum rules. These moments are then corrected for temperature inhomogeneities in the scattering volume. The proposed interpretation of scattering data is compared with the RPA result and with the standard Bhatnagar-Gross-Krook collisional model for the dynamic structure factor. It is shown that the obtained electron temperature values are closer but not equal to local thermodynamic equilibrium temperature values extracted from spectroscopic measurements.


The Different Impact of ERK Inhibition on Neuroblastoma, Astrocytoma, and Rhabdomyosarcoma Cell Differentiation.
Aberrant ERK activity can lead to uncontrolled cell proliferation, immortalization, and impaired cell differentiation. Impairment of normal cell differentiation is one of the critical stages in malignant cell transformation. In this study, we investigated a relationship between ERK tyrosine kinase activity and the main differentiation features (changes in cell morphology and expression of genes encoding differentiation markers and growth factor receptors) in SH-SY5Y neuroblastoma, U-251 astrocytoma, and TE-671 rhabdomyosarcoma cells. ERK activity was assessed using a reporter system that enabled live measurements of ERK activity in single cells. We demonstrated that suppression of ERK activity by selective ERK inhibitors, in contrast to a commonly used differentiation inducer, retinoic acid, leads to significant changes in TE-671 cell morphology and expression of the myogenic differentiation marker genes PROM1, MYOG, and PAX7. There was a relationship between ERK activity and morphological changes at an individual cell level. In this case, SH-SY5Y cell differentiation induced by retinoic acid was ERK-independent. We showed that ERK inhibition increases the sensitivity of TE-671 cells to the EGF, IGF-1, and NGF growth factors, presumably by reducing basal ERK activity, and to the BDNF growth factor, by increasing expression of the TrkB receptor.


Staphylococcus aureus skin infection recurrences among household members: an examination of host, behavioral, and pathogen-level predictors.
Many patients suffer from recurrent Staphylococcus aureus infections, but there are few data examining recurrence predictors. We followed adults and children after treatment for S. aureus skin infections and their household contacts in Los Angeles and Chicago. We surveyed subjects for S. aureus body colonization, household fomite contamination, and behavioral and clinical factors at baseline and 3 and 6 months later. Using repeated measures modeling, we examined host, pathogen, behavioral, and clinical factors associated with recurrence. Among 330 index subjects, 182 (55%) were infected with an isolate of the USA300 methicillin-resistant S. aureus (MRSA) genetic background. Recurrences occurred in 39% by month 3 and 51% by month 6. Among 588 household contacts, 10% reported a skin infection by month 3 and 13% by month 6. Among index subjects, recurrence was associated with (P < .05) Los Angeles site, diabetes, recent hospitalization, recent skin infection, recent cephalexin use, and household S. aureus or MRSA fomite contamination; recurrence was inversely associated with recent contact sports participation. In the multivariate model, independent predictors of recurrence in index patients were recent hospitalization, household MRSA fomite contamination, and lack of recent contact sports participation. Among household contacts, independent predictors of subsequent skin infection were Chicago site, antibiotic use in the prior year, and skin infection in the prior 3 months. In our longitudinal study, patients with a S. aureus skin infection were more likely to suffer a recurrence if household fomites were MRSA contaminated. Interventions to prevent recurrence may be enhanced by decontamination of household fomites.


Physiological plasticity of single neurons in auditory cortex of the cat during acquisition of the pupillary conditioned response: I. Primary field (AI).
The effects of conditioning on the discharges of single neurons in primary auditory cortex (AI) were determined during acquisition of the pupillary conditioned response in chronically prepared cats. Acoustic stimuli (1-s white noise or tone) were presented with electrodermal stimulation unpaired during a sensitization control phase followed by pairing during a subsequent conditioning phase. Stimulus constancy at the periphery was ensured by the use of neuromuscular blockade. Discharge plasticity developed rapidly for both evoked and background activity, the former attaining criterion faster than the latter. The pupillary dilation conditioned response was acquired at the same rate as were changes in evoked activity (i.e., 10-15 trials) and faster than background activity (i.e., 20-25 trials). Increases in background activity were correlated with increasing level of tonic arousal, as indexed by pretrial size of the pupil.


Treating Acute Cervical Radiodermatitis with Photobiomodulation Therapy: A Report of Two Cases.
Objective: The objective of this study was to report the application of photobiomodulation therapy (PBMT) in the treatment of two patients diagnosed with acute cervical radiodermatitis (RD) induced by radiotherapy. Background data: An undesirable effect of radiotherapy, RD often poses a limitation to the continuity of treatment that can negatively affect the control and prognosis of the disease. RD is frequently associated with pain and aesthetic impairment and can significantly influence quality of life. Many agents used to prevent and treat RD do not have sufficient scientific evidence to support its use. Materials and methods: In both clinical cases, the patients presented RD degree 3 and were in drug treatment, with no satisfactory response, and PBMT was started. Two diode lasers were used, with a dose of 35.71 J/cm2, 10 sec/point, 100 mW of power, and a beam area of 0.028 cm2 and dose of 27.77 J/cm2, 25 sec/point, 40 mW, and 0.036 cm2 beam area. Both lasers were applied at the wavelength of red, daily, in contact and perpendicular to the skin, to deliver 1 J/point/1.5 cm, which covered the entire area affected with RD. Results: The PBMT made possible an expressive improvement in the healing process and reduction of painful symptoms associated with RD. Conclusions: Although PBMT facilitated healing and reduced pain experienced with RD, randomized controlled trials are needed to evaluate all of its possible benefits.


Away Rotations in Obstetrics and Gynecology: A Survey of Program Directors.
To evaluate residency program director views on the purpose and value of an away rotation for students applying to a residency application in Obstetrics and Gynecology (OBGYN). The Council on Resident Education in Obstetrics and Gynecology administered a 28-question survey to current U.S. program directors in OBGYN in 2022. Program directors were asked if they offered away rotations to visiting medical students and if so, what the purpose the rotation played in their application process and whether rotating students were automatically offered a residency interview. Program characteristics such as program size, geographic location, and program type (university, community, or military based) were ascertained. A test of proportions was utilized to understand the relationship between program description and survey responses. Seventy-nine percent (224/285) of OBGYN PDs responded to the survey and consented to participation. Programs were representative of the types of training program, size of programs, and geographic location. Of respondents, 77.2% (173/224) of PDs indicated that away rotations were offered at their institution, but only 26.6% (46/173) of residency PDs assessed prospective candidates for away electives. The opportunity to provide students an audition for a residency position was the most common reason to offer an elective. Only 34.7% (60/173) of OBGYN PDs guaranteed an interview to students who completed away electives at their institution. The majority (118/173, 68.2%) of PDs indicated less than 25% of their current residents had completed an away rotation with their program. Many residency programs offered away electives to prospective applicants, but the majority did not personally assess applicants for competitiveness or guarantee interviews to students completing electives. To increase transparency in the application process, programs should publicize the purpose of away rotations and provide information on the number of interviews granted to students who complete away rotations.


Trans-Lycopene and β-Cryptoxanthin Intake and Stomach Cancer in Vietnamese Men: A Pilot Case-Control Study.
To examine the association between dietary intake of Trans-Lycopene and β-Cryptoxanthin and stomach cancer in Vietnamese men. A case-control study including 80 male incident stomach cancer cases and 146 male controls was performed in a general hospital in Viet Nam. A validated semi-quantitative food frequency (SQFFQ) and demographic lifestyle questionnaire were designed, and venous blood samples were collected to determine H. pylori status by IgG ELISA. Nutrient intake was converted using the data of SQFFQ and the Nutritive Composition Table of Vietnamese Foods, updated in 2019. The respective associations between Trans-Lycopene and β-Cryptoxanthin intake and stomach cancer were examined using unconditional logistic regression analysis with adjustments for possible cofactors. Both Trans-Lycopene and β-Cryptoxanthin intake and stomach cancer showed a significantly inverse association, tertile-3 versus tertile-1, (OR = 0.15, 95%CI: 0.06-0.35, p trend = 0.00) and (OR = 0.34, 95%CI: 0.14-0.79, p trend = 0.02, respectively). For Trans-Lycopene intake stratifying by H. pylori status remained the benefit effect against stomach cancer among H. pylori-negative participants (OR = 0.15, 95%CI: 0.03-0.69, p trend = 0.02) and H. pylori-positive participants (OR = 0.13, 95%CI: 0.04-0.42, p trend = 0.00). Both Trans-Lycopene and β-Cryptoxanthin intake showed a strong protective effect against stomach cancer. The findings suggest that these two types of fat-soluble micronutrients would be considered as an anti-cancer therapy for both primary and secondary prevention.


Preventing opioid-related deaths in children undergoing surgery.
Tonsillectomy is one of the most commonly done surgical procedures in children. There are many unreported deaths following tonsillectomy in children due to opioids. Genetic variations in liver microenzyme, CYP2D6, had been associated with some of the deaths. Opioids metabolized by CYP2D6 include codeine, tramadol, hydrocodone, and oxycodone. Ultrarapid metabolizers and some extensive metabolizers of CYP2D6 relatively produce more active opioid metabolites resulting in life-threatening adverse effects, especially in young children. Young and obese children with history of sleep apnea are at higher risk of developing serious opioid-related respiratory depression. The adverse outcomes can be avoided and the safety of pain management can be improved by CYP2D6 genetic testing before prescribing these opioids or by using alternative analgesics.


Fine particle emissions from on-road vehicles in the Zhujiang Tunnel, China.
Little is known about the characteristics of particulate matter emissions from vehicles in China, although such information is critical in source apportionment modeling, emission inventories, and health effect studies. In this paper, we report a comprehensive characterization of PM2.5 emissions in the Zhujiang Tunnel in the Pearl River Delta region of China. The chemical speciation included elemental carbon, organic carbon, inorganic ions, trace elements, and organic compounds. The emission factors of individual species and their relative distributions were obtained for a mixed fleet of heavy-duty vehicles (19.8%) and light-duty vehicles (80.2%). In addition, separate emission factors of PM2.5 mass, elemental carbon, and organic matter for heavy-duty vehicles and light-duty vehicles also were derived. As compared to the results of other tunnel studies previously conducted, we found that the abundances and distributions of the trace elements in PM2.5 emissions were more varied. In contrast, the characteristics of the trace organic compounds in the PM2.5 emissions in our study were consistent with characteristics found in other tunnel studies and dynamometer tests. Our results suggested that vehicular PM2.5 emissions of organic compounds are less influenced by the geographic area and fleet composition and thereby are more suitable for use in aerosol source apportionment modeling implemented across extensive regions.


Scanning picosecond tunable laser system for simulating MeV heavy ion-induced charge collection events as a function of temperature.
A new methodology for using scanning picosecond laser microscopy to simulate cosmic ray induced radiation effects as a function of temperature is described in detail. The built system is centered on diffraction-limited focusing of the output from a broadband (690-960 nm) ultrafast Ti:sapphire Tsunami laser pumped by a 532 nm Millennia laser. An acousto-optic modulator is used to provide pulse picking down to event rates necessary for the technologies and effects under study. The temperature dependence of the charge generation process for ions and photons is briefly reviewed and the need for wavelength tunability is discussed. An appropriate wavelength selection is critical for proper emulation of ion events over a wide temperature range. The system developed is detailed and illustrated by way of example on a deep-submicron complementary metal-oxide semiconductor test structure.


The RNase protection assay.
The RNase protection assay is a sensitive method for transcription start-site localization. It begins with an RNA probe that is uniformly labeled by incorporation of one [α-(32)P]NTP, usually [α-(32)P]UTP. The RNA probe is synthesized by bacteriophage RNA polymerase (SP6, T7, or T3), which initiates transcription from specific phage promoters that have been engineered into a number of common plasmid vectors. The plasmid template contains a genomic DNA fragment spanning the region thought to contain the transcription start site for the gene of interest. This genomic fragment is subcloned into the plasmid downstream of the phage promoter in the antisense orientation, so that a portion of the 5' end of the resulting RNA probe will be complementary to the mRNA of interest. The radiolabeled probe is annealed to cytoplasmic or total cellular mRNA purified from the cells of interest, with the hybridization reaction proceeding for several hours or overnight. RNase A and/or RNase T1 is then added to the hybridization reactions. These nucleases digest the single-stranded overhang regions of RNA molecules, but RNA-RNA hybrids are resistant to cleavage. This resistance forms the conceptual basis for the procedure; the region of the probe that anneals to the specific mRNA will be resistant to digestion. The length of the resistant region of the probe will correspond to the distance from the 5' end of the probe to the transcription start site. The size of the resistant fragment can be determined by electrophoresis on a high-resolution, denaturing polyacrylamide gel.


Increasing the priority of mental health in Africa: findings from qualitative research in Ghana, South Africa, Uganda and Zambia.
Despite the high prevalence of mental illness, mental health remains a low priority in Africa. There has been no investigation of the views of stakeholders in Africa on why this is and what can be done. This paper reports a comparison of the views of stakeholders in Ghana, South Africa, Uganda and Zambia, focusing on the priority given to mental health by the government at the national and regional/province levels. We conducted semi-structured interviews with key stakeholders and used a two-stage approach to analysis: firstly framework analysis in each study country, followed by comparative analysis of the country data. Mental health was largely considered a low priority at national and regional/provincial levels in all four countries. We identified nine factors affecting the priority of mental health, which were grouped into three categories: legitimacy of the problem, feasibility of response and support for response. Respondents put forward a range of experiences and suggestions for increasing the priority given to mental health. We conclude with broad suggestions to raise the priority of mental health. These suggestions are particularly relevant as mental health increases in priority on the international agenda, in order to inform advocacy for increased priority for mental health in Africa.


Benign Fibro-Osseous Lesions of the Craniofacial Area in Children and Adolescents: A Review.
Benign fibro-osseous lesions (BFOL) of the craniofacial area are represented by a variety of morphologic processes that are characterized by pathologic ossifications and calcifications in association with a hypercellular fibroblastic marrow element. The current classification includes neoplasms, developmental dysplastic lesions and inflammatory/reactive processes [5]. The final diagnosis depends on-clinical, radiological and pathological features. The clinico-pathologic features of this heterogeneous group of diseases are presented in this article.


The Nogo/Nogo Receptor (NgR) Signal Is Involved in Neuroinflammation through the Regulation of Microglial Inflammatory Activation.
Microglia have been proposed to play a pivotal role in the inflammation response of the CNS by expressing a range of proinflammatory enzymes and cytokines under pathological stimulus. Our previous study has confirmed that Nogo receptor (NgR), an axon outgrowth inhibition receptor, is also expressed on microglia and regulates cell adhesion and migration behavior in vitro. In the present study, we further investigated the proinflammatory effects and possible mechanisms of Nogo on microglia in vitro. In this study, Nogo peptide, Nogo-P4, a 25-amino acid core inhibitory peptide sequence of Nogo-66, was used. We found that Nogo-P4 was able to induce the expression of inducible nitric-oxide synthase and cyclooxygenase-2 and the release of proinflammatory cytokines, including IL-1β, TNF-α, NO, and prostaglandin E2 in microglia, which could be reversed by NEP1-40 (Nogo-66(1-40) antagonist peptide), phosphatidylinositol-specificphospholipase C, or NgR siRNA treatment. After Nogo-P4 stimulated microglia, the phosphorylation levels of NF-κB and STAT3 were increased obviously, which further mediated microglia expressing proinflammatory factors induced by Nogo-P4. Taken together, we concluded that Nogo peptide could directly take part in CNS inflammatory process by influencing the expression of proinflammatory factors in microglia, which were related to the NF-κB and STAT3 signal pathways. Besides neurite outgrowth restriction, the Nogo/NgR signal might be involved in multiple processes in various inflammation-associated CNS diseases.


Differentiating and apoptotic dose-dependent effects in (-)-alpha-bisabolol-treated human endothelial cells.
The effect on angiogenesis of (-)-alpha-bisabolol [(-)-6-methyl-2-(4-methyl-3-cyclohexen-1-yl)-5-hepten-2-ol] (1), a widely distributed plant sesquiterpene alcohol, was investigated for the first time. Human endothelial cells treated with 1 were analyzed for their ability to differentiate and organize in microvessels and for their sensitivity to this compound in terms of cytotoxicity and cell growth inhibition. Within 24 h of the treatment with 5 microM 1, cells underwent massive death. Apoptosis induction was responsible for cytotoxicity triggered by 1 as revealed by the release of cytochrome c from the mitochondria, reduction of the Bcl-2/Bax ratio, and caspase 3 activation. At a lower, non-apoptotic concentration (0.25 microM), 1 showed a differentiating effect resulting in growth inhibition, invasiveness reduction, and tubule stabilization.


Induction of multiple myeloma-specific cytotoxic T lymphocyte stimulation by dendritic cell pulsing with purified and optimized myeloma cell lysates.
We investigated the possibility of immunotherapy for multiple myeloma (MM) using myeloma-specific cytotoxic T lymphocytes (CTLs) that were stimulated in vitro by dendritic cells (DCs) pulsing with purified and optimized myeloma lysates. CD14(+) cells were cultured in the presence of GM-CSF and IL-4. On day 6, the immature DCs were pulsed with the purified myeloma cell lysates, and then maturation of the DCs was induced by the addition of a cytokine cocktail. There were no differences in the phenotypic expressions of mature DCs that were generated by pulsing with CD138(+) cell lysates or total cell lysates. In optimization of the concentration of myeloma lysates, DCs pulsed with 10 microg/mL of myeloma lysate had greater allogeneic T-cell stimulatory capacities than those pulsed with higher concentrations of myeloma lysates. The CTL lines generated by DCs pulsed with myeloma lysates demonstrated potent cytotoxic activities against autologous target cells, but not against HLA-A2(-) cell lines or K562 cell lines. The DCs pulsed with myeloma lysates demonstrated a higher stimulatory capacity for autologous CTL compared with mature nonpulsed DCs. These results suggested that the DCs pulsed with purified and optimized myeloma cell lysates could generate potent myeloma-specific CTLs for approaches in MM.


Outcome of subacute stroke rehabilitation: a randomized controlled trial.
Organized acute stroke treatment reduces mortality, functional deficits, and the need of institutionalization after stroke. It is largely unknown whether the effects of treatment are due to early or subacute efforts. The aim of this randomized, controlled study was to test the hypothesis that rehabilitation of stroke patients in the subacute phase in a hospital rehabilitation unit is beneficial in reducing death and dependency and increasing health-related quality of life. 251 patients initially treated in the hospital were randomized to subacute rehabilitation in a hospital rehabilitation unit (n = 127) or to the health services in the municipality (n = 124) and were followed up for 7 months. The combined outcome of patients being dead or dependent (Barthel Index score of < 75) was 23% in the hospital group and 38% in the municipality group (P=.01). Seven-month survival rates were 90.6% and 83.9% (P=.11), respectively. Dependency in activities of daily living was 12.6% in the hospital group and 25.0% in the municipality group (P=.07). Patients with a BI score of < 50 before rehabilitation had significantly better outcome in the hospital rehabilitation unit, with fewer patients becoming dependent (P=.005) and patients having higher Scandinavian Stroke Scale (P=.026) and BI scores (P=.005). No significant differences in health-related quality of life were found. Many patients treated in the municipalities (30%) did not receive any organized rehabilitation in this study. Subacute rehabilitation of stroke patients in a hospital-based rehabilitation unit improves outcome. Patients with moderate or severe stroke appear to benefit most.


Differential effect of dopa and subthalamic stimulation on vestibular activity in Parkinson's disease.
Postural disturbances in advanced Parkinson's disease are less responsive to therapy than other cardinal motor signs. The vestibulocollic reflex represents one brain-stem neuronal circuit involved in postural adjustments. The objective of this study was to investigate the vestibulocollic reflex in parkinsonian patients and the effects of subthalamic stimulation and dopa by recording vestibular-evoked myogenic potentials. After overnight withdrawal of medication, 20 patients with Parkinson's disease with (6 men, 4 women; mean age, 64.4 ± 2.2 years) or without (8 men, 2 women; mean age, 62.7 ± 3.9 years) implanted subthalamic electrodes in different treatment conditions were compared with 10 age-matched controls (5 men, 5 women; mean age, 59.6 ± 2.4 years). Vestibular-evoked myogenic potentials were recorded by electromyographic surface electrodes applied to both sternocleidomastoid muscles (band-pass filter, 8-1600 Hz; sampling rate, 5 kHz) and averaged in response to bilateral auditory tone bursts (120 dB SPL; sine waves, 7 ms; 1000 Hz) applied through earphones. Adjusted vestibular-evoked myogenic potential amplitudes were significantly smaller in parkinsonian patients than in controls, in particular in patients without surgery. Administration of dopa, but not subthalamic stimulation, significantly increased amplitudes. Onset latencies were similar for all groups and treatment conditions. Decreased vestibular-evoked myogenic potential amplitudes in parkinsonian patients suggest reduced vestibular nuclei excitability within the brain stem, which is modulated by dopa but not by subthalamic stimulation. This suggests different pathways for the action of both treatment modalities in Parkinson's disease and may explain clinical differences in terms of postural disturbances. © 2012 Movement Disorder Society.


Metabolism of the tryptamine-derived new psychoactive substances 5-MeO-2-Me-DALT, 5-MeO-2-Me-ALCHT, and 5-MeO-2-Me-DIPT and their detectability in urine studied by GC-MS, LC-MSn , and LC-HR-MS/MS.
Many N,N-dialkylated tryptamines show psychoactive properties and were encountered as new psychoactive substances. The aims of the presented work were to study the phase I and II metabolism and the detectability in standard urine screening approaches (SUSA) of 5-methoxy-2-methyl-N,N-diallyltryptamine (5-MeO-2-Me-DALT), 5-methoxy-2-methyl-N-allyl-N-cyclohexyltryptamine (5-MeO-2-Me-ALCHT), and 5-methoxy-2-methyl-N,N-diisopropyltryptamine (5-MeO-2-Me-DIPT) using gas chromatography-mass spectrometry (GC-MS), liquid chromatography coupled with multistage accurate mass spectrometry (LC-MSn ), and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS). For metabolism studies, urine was collected over a 24 h period after administration of the compounds to male Wistar rats at 20 mg/kg body weight (BW). Phase I and II metabolites were identified after urine precipitation with acetonitrile by LC-HR-MS/MS. 5-MeO-2-Me-DALT (24 phase I and 12 phase II metabolites), 5-MeO-2-Me-ALCHT (24 phase I and 14 phase II metabolites), and 5-MeO-2-Me-DIPT (20 phase I and 11 phase II metabolites) were mainly metabolized by O-demethylation, hydroxylation, N-dealkylation, and combinations of them as well as by glucuronidation and sulfation of phase I metabolites. Incubations with mixtures of pooled human liver microsomes and cytosols (pHLM and pHLC) confirmed that the main metabolic reactions in humans and rats might be identical. Furthermore, initial CYP activity screenings revealed that CYP1A2, CYP2C19, CYP2D6, and CYP3A4 were involved in hydroxylation, CYP2C19 and CYP2D6 in O-demethylation, and CYP2C19, CYP2D6, and CYP3A4 in N-dealkylation. For SUSAs, GC-MS, LC-MSn , and LC-HR-MS/MS were applied to rat urine samples after 1 or 0.1 mg/kg BW doses, respectively. In contrast to the GC-MS SUSA, both LC-MS SUSAs were able to detect an intake of 5-MeO-2-Me-ALCHT and 5-MeO-2-Me-DIPT via their metabolites following 1 mg/kg BW administrations and 5-MeO-2-Me-DALT following 0.1 mg/kg BW dosage. Copyright © 2017 John Wiley & Sons, Ltd.


Nodal tumor volume as a prognostic factor for oral squamous cell carcinoma-a systematic review.
Oral squamous cell carcinoma (OSCC) is a complex disease with a high potential for lymph node metastasis and poor survival rates. Accurate nodal staging is crucial for prognostic assessment and treatment planning in OSCC. Recent research has suggested that nodal tumor volume (NTV) may be a more accurate indicator of nodal disease burden than traditional staging methods. However, the prognostic significance of NTV in OSCC remains unclear. This systematic review aims to evaluate the existing evidence on the relationship between NTV and prognosis in OSCC. A comprehensive search of electronic databases was conducted, and studies meeting inclusion criteria were critically appraised and synthesized. Our review identified 23 studies that investigated the prognostic significance of NTV in OSCC. The majority of studies reported that larger NTV was associated with poorer survival outcomes, although the strength of the association varied. The review also identified several areas for future research, including the standardization of NTV measurement and the integration of NTV into the broader landscape of OSCC management. In conclusion, our review suggests that NTV holds promise as a novel prognostic factor in OSCC, but more research is needed to fully elucidate its potential and inform clinical decision-making.


Hierarchical additive effects on heterosis in rice (Oryza sativa L.).
Exploitation of heterosis in crops has contributed greatly to improvement in global food and energy production. In spite of the pervasive importance of heterosis, a complete understanding of its mechanisms has remained elusive. In this study, a small test-crossed rice population was constructed to investigate the formation mechanism of heterosis for 13 traits. The results of the relative mid-parent heterosis and modes of inheritance of all investigated traits demonstrated that additive effects were the foundation of heterosis for complex traits in a hierarchical structure, and multiplicative interactions among the component traits were the framework of heterosis in complex traits. Furthermore, new balances between unit traits and related component traits provided hybrids with the opportunity to achieve an optimal degree of heterosis for complex traits. This study dissected heterosis of both reproductive and vegetative traits from the perspective of hierarchical structure for the first time. Additive multiplicative interactions of component traits were proven to be the origin of heterosis in complex traits. Meanwhile, more attention should be paid to component traits, rather than complex traits, in the process of revealing the mechanism of heterosis.


Pediatric hematology/oncology physician and nurse practitioner attitudes towards the COVID-19 vaccines: A qualitative study.
As of 05/28/2021, SARS-CoV-2 (COVID-19) had caused 3.9 million infections in the United States (US) pediatric population since its discovery in December of 2019. The development and expansion of vaccination has markedly changed the shape of the epidemic. In this qualitative study, we report on pediatric hematology/oncology provider views on the COVID-19 vaccine prior to approval in the adolescent population <16 years of age. Results from interviews with 20 providers across the state of Indiana showed that most were supportive of the COVID-19 vaccine for healthy adults. However, the majority also expressed a need to see more data on the safety and effectiveness of COVID-19 vaccinations in pediatric hematology/oncology populations. While they recognized the public health importance of vaccination, their duty to protect their patients led to a need for more specific safety and efficacy data.


Evaluation of deformable image registration for contour propagation between CT and cone-beam CT images in adaptive head and neck radiotherapy.
Deformable image registration (DIR) is a critical technic in adaptive radiotherapy (ART) to propagate contours between planning computerized tomography (CT) images and treatment CT/Cone-beam CT (CBCT) image to account for organ deformation for treatment re-planning. To validate the ability and accuracy of DIR algorithms in organ at risk (OAR) contours mapping, seven intensity-based DIR strategies are tested on the planning CT and weekly CBCT images from six Head & Neck cancer patients who underwent a 6 ∼ 7 weeks intensity-modulated radiation therapy (IMRT). Three similarity metrics, i.e. the Dice similarity coefficient (DSC), the percentage error (PE) and the Hausdorff distance (HD), are employed to measure the agreement between the propagated contours and the physician delineated ground truths. It is found that the performance of all the evaluated DIR algorithms declines as the treatment proceeds. No statistically significant performance difference is observed between different DIR algorithms (p> 0.05), except for the double force demons (DFD) which yields the worst result in terms of DSC and PE. For the metric HD, all the DIR algorithms behaved unsatisfactorily with no statistically significant performance difference (p= 0.273). These findings suggested that special care should be taken when utilizing the intensity-based DIR algorithms involved in this study to deform OAR contours between CT and CBCT, especially for those organs with low contrast.


Thermally cleavable surfactants based on furan-maleimide Diels-Alder adducts.
Two new surfactant molecules are reported that contain thermally labile Diels-Alder adducts connecting the hydrophilic and hydrophobic sections of each molecule. The two surfactants possess identical hydrophobic dodecyl tail segments but have phenol and carboxylic acid hydrophilic headgroups, respectively. Deprotonation with potassium hydroxide affords the formation of water-soluble surfactants. Room temperature aqueous solutions of both surfactants exhibit classical surface-active agent behavior similar to common analagous alkylaryl surfactant molecules. Critical micelle concentrations have been determined for each surfactant through dynamic surface tension and dye solubilization techniques. Small-angle neutron scattering measurements of the aqueous surfactant solutions indicate the presence of spherical micelles with radii of 16.5 angstroms for the carboxylate and 18.8 angstroms for the phenolate. When these surfactants are exposed to elevated temperatures (>50 degrees C), the retro Diels-Alder reaction occurs, yielding hydrophilic and hydrophobic fragments. Aqueous solutions of each surfactant subsequently exhibit a loss of all surface-active behavior and the micellar aggregates are no longer detectable.


Genome-Wide Analysis of the DNA Methylation Profile Identifies the Fragile Histidine Triad (FHIT) Gene as a New Promising Biomarker of Crohn's Disease.
Inflammatory bowel disease is known to be associated with a genetic predisposition involving multiple genes; however, there is growing evidence that abnormal interactions with environmental factors, particularly epigenetic factors, can also significantly contribute to the development of inflammatory bowel disease (IBD). Although many genome-wide association studies have been performed to identify the genetic changes underlying the pathogenesis of Crohn's disease, the role of epigenetic alterations based on molecular complications arising from Crohn's disease (CD) is poorly understood. We employed an unbiased approach to define DNA methylation alterations in colonoscopy samples from patients with CD using the HumanMethylation450K BeadChip platform. Technical and functional validation was performed by methylation-specific PCR (MSP) and bisulfite sequencing of a validation set of 207 patients with CD samples. Immunohistochemistry (IHC) analysis was performed in the representative sample sets. DNA methylation profile in CD revealed that 135 probes (24 hypermethylated and 111 hypomethylated probes) were differentially methylated. We validated the methylation levels of 19 genes that showed hypermethylation in patients with CD compared with normal controls. We uniquely identified that the fragile histidine triad (FHIT) gene was hypermethylated in a disease-specific manner and its protein level was downregulated in patients with CD. Pathway analysis of the hypermethylated candidates further suggested putative molecular interactions relevant to IBD pathology. Our data provide information on the biological and clinical implications of DNA hypermethylated genes in CD, identifying FHIT methylation as a promising new biomarker for CD. Further study of the role of FHIT in IBD pathogenesis may lead to the development of new therapeutic targets.


Comparison of histologic and immunologic heterogeneity of non-Hodgkin's lymphomas.
The lymphocyte surface marker phenotype in 11 selected cases of non-Hodgkin's lymphomas was determined with anti-immunoglobulin and mouse monoclonal antibodies against human lymphocyte antigens. A complement-mediated cell cytotoxicity assay on suspensions of the tumor cells was compared with an indirect immunoperoxidase technique on frozen tissue sections. Both methods gave good results in tumors with a uniform cell population, but the frozen section technique was superior in heterogeneous tumors. The six B-cell neoplasms were heterogeneous with respect to expression of surface immunoglobulin and Ia antigens. The five T-cell tumors were morphologically heterogeneous and also highly variable in their expression of different T-cell specific antigens.


[Quinolones].
New quinolones are notable for their high level of antibacterial activity, especially against gram-negative pathogens, and also for their specific pharmacokinetics involving good bioavailability after oral administration, high distribution volumes and a long elimination time. In view of these properties the more recent quinolones can be regarded as on a par with the modern beta-lactam antibiotics and aminoglycosides, which, especially through the possibility of oral administration in infections with problem organisms such as Pseudomonas aeruginosa or Serratia, represent a therapeutic advance. To maintain this advance the indications for therapy must be approached in a restrictive and critical spirit; the newer quinolones are only rarely the drugs of choice and should be held in reserve for complicated infections of the respiratory tract, the intestinal tract, the urinary tract and the bones. In regard to tolerance, particular consideration should be given to the specific CNS intolerance reaction.


Patterns of slow transport in sensory nerves.
An examination of the pattern of outflow of radioactivity in sciatic nerves was made at times from 1 to 82 days in the rat and up to 132 days in the cat after injecting the L5 and L7 dorsal root ganglia, respectively, with 3H-leucine. Slow waves moving at a rate of 1-2 mm/day were looked for on the basis of their reported presence in the motor fibers of the rat. A consistent pattern of slow waves was not seen in the cat or rat sensory fibers of the sciatic nerves nor was evidence of a slow wave found in the cat dorsal columns. Irregularities in the pattern of outflow which at times appeared as "waves" did so in an irregular fashion, a pattern inconsistent with a steady progression of slow waves in the fibers. The decrease of radioactivity appearing first near the ganglia helps create the impression of a wave along with irregular decreases in the overall levels of radio-activity with time. The results were explained on the basis of the unitary hypothesis. The labeled components are considered to be moved down the fiber by the fast transport mechanism, those components dropping off locally in the fibers early on, constituting the slow wave. As those components turn over locally in the various organelles of fiber and are further redistributed, they may at times give rise to what appears as waves.


Favorable Outcomes after Implantation of Biodegradable Polymer Coated Sirolimus-Eluting Stents in Diabetic Population: Results from INDOLIMUS-G Diabetic Registry.
Objective. The main aim is to evaluate safety, efficacy, and clinical performance of the Indolimus (Sahajanand Medical Technologies Pvt. Ltd., Surat, India) sirolimus-eluting stent in high-risk diabetic population with complex lesions. Methods. It was a multicentre, retrospective, non-randomized, single-arm study, which enrolled 372 diabetic patients treated with Indolimus. The primary endpoint of the study was major adverse cardiac events (MACE), which is a composite of cardiac death, target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), and stent thrombosis (ST). The clinical follow-ups were scheduled at 30 days, 6 months, and 9 months. Results. The mean age of the enrolled patients was 53.4 ± 10.2 years. A total of 437 lesions were intervened successfully with 483 stents (1.1 ± 0.3 per lesion). There were 256 (68.8%) male patients. Hypertension and totally occluded lesions were found in 202 (54.3%) and 45 (10.3%) patients, respectively. The incidence of MACE at 30 days, 6 months and 9 months was 0 (0%), 6 (1.6%), and 8 (2.2%), respectively. The event-free survival at 9-month follow-up by Kaplan Meier method was found to be 97.8%. Conclusion. The use of biodegradable polymer coated sirolimus-eluting stent is associated with favorable outcomes. The results demonstrated in our study depict its safety and efficacy in diabetic population.


OUTER RETINA CAPILLARY INVASION AND ELLIPSOID ZONE LOSS IN MACULAR TELANGIECTASIA TYPE 2 IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
Macular telangiectasia Type 2 (MacTel2) is a neurodegenerative and vascular disease limited to the macular area, resulting ultimately in Muller cell and photoreceptor loss and intra or subretinal proliferation. Optical coherence tomography angiography was used to correlate the proliferation of capillaries in the outer retina with the topography of the ellipsoid zone (EZ) loss. Thirty eyes of 15 patients with MacTel2 were examined using optical coherence tomography angiography. Images of the superficial and deep capillary plexus were analyzed and compared with en-face angio-flow images of the outer retina and en-face image of the EZ. Twenty-one eyes were available for the study, including 12 with invasion of the outer retina capillary on optical coherence tomography angiography but without subretinal neovascularization. The outer retina capillary proliferation had a radial pattern in eight cases, formed loops in four, and was circumscribed to an area of EZ loss on en-face images. In nine cases, there was no outer capillary proliferation including two cases with foci of EZ loss. Optical coherence tomography angiography shows capillary proliferation in the outer retina corresponding to areas of EZ loss, which could be a useful marker to monitor the efficacy of possible treatments in MacTel2 disease.


Comparison of effects of PKA catalytic subunit on I(h) and calcium channel currents in rat dorsal root ganglion cells.
We investigated whether PKA-induced phosphorylation was involved in regulation of hyperpolarization-activated current (I(h)) in rat dorsal root ganglion (DRG) cells. We examined the effect of the catalytic subunit of PKA (PKAc) on I(h) and confirmed an effect of PKAc on Ca(2+) channel currents carried by Ba(2+) (I(Ba)) in identical neurons as a positive control of PKA activity. After the start of recording, amplitudes of I(Ba) gradually decreased (rundown). An intracellular application of ATP reduced the rundown of I(Ba) and induced a depolarizing shift of I(h) activation. The former was partially reversed by PKI but the latter was not affected. An intracellular application of PKAc also prevented the rundown of I(Ba) and this effect was potentiated by okadaic acid (OA). The application of PKAc and OA in combination did not change the electrophysiological properties of I(h) although a potentiating effect on I(Ba) was observed in the same neurons. The application of 2-mM ATP in addition to PKAc and OA did not result in an additional potentiation of I(Ba), but shifted the activation curve of I(h) positively. These results suggested that PKA-induced phosphorylation was not involved in the modulatory mechanisms of I(h) in rat DRG neurons.


Energy based pharmacophore mapping of HDAC inhibitors against class I HDAC enzymes.
Histone deacetylases (HDACs) are important class of enzymes that deacetylate the ε-amino group of the lysine residues in the histone tails to form a closed chromatin configuration resulting in the regulation of gene expression. Inhibition of these HDACs enzymes have been identified as one of the promising approaches for cancer treatment. The type-specific inhibition of class I HDAC enzymes is known to elicit improved therapeutic effects and thus, the search for promising type-specific HDAC inhibitors compunds remains an ongoing research interest in cancer drug discovery. Several different strategies are eployed to identify the features that could identify the isoform specificity factors in these HDAC enzymes. This study combines the insilico docking and energy-optomized pharmacophore (e-pharmacophore) mapping of several known HDACi's to identify the structural variants that are significant for the interactions against each of the four class I HDAC enzymes. Our hybrid approach shows that all the inhibitors with at least one aromatic ring in their linker regions hold higher affinities against target enzymes, while those without any aromatic rings remain as poor binders. We hypothesize the e-pharmacophore models for the HDACi's against all the four Class I HDAC enzymes which are not reported elsewhere. The results from this work will be useful in the rational design and virtual screening of more isoform specific HDACi's against the class I HDAC family of proteins.


Telomere length and hTERT in mania and subsequent remission.
The findings of telomere length (TL) studies in bipolar disorder (BD) are controversial. The aim of the present study was to detect TL, human telomerase reverse transcriptase (hTERT), and brain derived neurotrophic factor (BDNF) in severe mania and subsequent remission. Twenty-one medication-free male patients and 20 age and gender matched controls were recruited. The patients were followed in the inpatient clinic, and comparisons were made between the same patients in their remission state and controls. Patients received lithium plus antipsychotics during the follow-up period. Quantitative real-time polymerase chain reaction was performed to verify leukocyte TL and whole blood hTERT gene expression levels. Serum BDNF levels were verified by enzyme-linked immunosorbent assay (ELISA). Compared to controls, manic patients presented shorter telomeres (p < 0.001) whose length increased with treatment (p = 0.001). Patients in the late stages showed shorter TL than those in the early stages and controls (p < 0.001). hTERT gene expression levels were up-regulated in mania and remission compared to controls (p = 0.03 and p = 0.01, respectively). BDNF changes did not reach statistically significant levels. TL and hTERT gene expression might reflect a novel aspect of BD pathophysiology and TL might represent a novel biomarker for BD staging.


Selective depletion of human natural killer cells on monolayers of target cells.
The specificity of human natural killer (NK) cells recently has been evaluated by examining direct cytotoxic reactions against a variety of target cells and by cold target inhibition assays. Although these studies have provided evidence for the multiplicity of NK antigens, they did not indicate whether NK cells were heterogeneous, with subpopulations recognizing different specificities. We have examined this issue by using a tumor cell-monolayer adsorption technique that allowed the removal of NK-reactive cells by adsorption to monolayers of various NK-sensitive target cells. After depletion of cells capable of binding to a particular monolayer, the remaining cells were tested for cytotoxicity against a panel of 5 target cells. With several donors, the monolayers were effective in depleting most or all reactivity against the same target cell but only removed a portion of reactivity against some other target cells. The patterns of reactivity after adsorption, although varying among the donors, were consistent upon repeat testing of the same donor. To account for the reactivities of the various donors that remained after adsorption, it was necessary to postulate at least 7 antigenic specificities. These results indicate that human NK cells may be heterogeneous, with each subpopulation recognizing different antigenic specificities on target cells.


In Situ and in Operando Characterization of Mixing Dynamics in Liquid-Phase Reactions by 129 Xe NMR Spectroscopy.
129 Xe NMR spectroscopy is applied under in situ and in operando conditions to study the mixing process in a multicomponent liquid mixture with partially miscible components. The process of mixing of an oil-methanol mixture was triggered by an industrially relevant catalytic transesterification reaction to form fatty acid methyl esters and glycerol. Up to date, kinetic limitations in liquid-phase reactions originating from the poor miscibility of the reacting species have been addressed solely under ex situ conditions, typically by chromatography. In the approach presented here, xenon gas, solvated in the reacting species, acts as a sensor, providing information on the progress of mixing and on the composition during the course of the catalytic reaction. We believe that this study offers a new tool to the set of established techniques for addressing mixing and/or separation processes in liquids, including but not limited to the ones resulting from catalytic reactions.


Asymmetric anti-aldol addition of achiral ketones via chiral N-amino cyclic carbamate hydrazones.
The asymmetric anti-aldol addition of ketone-derived donors and aldehyde acceptors is described. Asymmetric induction is achieved through the use of chiral N-amino cyclic carbamate (ACC) auxiliaries. The transformation exhibits essentially perfect anti-diastereoselectivity and enantioselectivity, and has the unusual feature of proceeding via thermodynamic, rather than kinetic control.


Proteomic analysis of skeletal muscle in insulin-resistant mice: response to 6-week aerobic exercise.
Aerobic exercise has beneficial effects on both weight control and skeletal muscle insulin sensitivity through a number of specific signaling proteins. To investigate the targets by which exercise exerts its effects on insulin resistance, an approach of proteomic screen was applied to detect the potential different protein expressions from skeletal muscle of insulin-resistant mice after prolonged aerobic exercise training and their sedentary controls. Eighteen C57BL/6 mice were divided into two groups: 6 mice were fed normal chow (NC) and 12 mice were fed high-fat diet (HFD) for 10 weeks to produce an IR model. The model group was then subdivided into HFD sedentary control (HC, n = 6) and HFD exercise groups (HE, n = 6). Mice in HE group underwent 6 weeks of treadmill running. After 6 weeks, mice were sacrificed and skeletal muscle was dissected. Total protein (n = 6, each group) was extracted and followed by citrate synthase, 2D proteome profile analysis and immunoblot. Fifteen protein spots were altered between the NC and HC groups and 23 protein spots were changed between the HC and HE groups significantly. The results provided an array of changes in protein abundance in exercise-trained skeletal muscle and also provided the basis for a new hypothesis regarding the mechanism of exercise ameliorating insulin resistance.


Herniation of the singular nerve into the round window niche.
We report two cases of herniation of the singular nerve into the round window niche and one case of bony dehiscence without herniation between the round window niche and the posterior canal ampulla. It is believed that the middle ear and the inner ear are completely separate. However, in the temporal bone of a 10- to 15-week-old human fetus, a communication between the round window niche and the posterior canal ampulla is observed. Later, the mesenchymal tissue in the communication is replaced by cartilage from near the posterior canal ampulla. If the communication does not fill with cartilage, ossification is not able to begin behind the posterior canal crista. When there is bony dehiscence behind the crista, the singular nerve fibers are easily pressed out by ossified endosteal bone and herniated into the round window niche.


Vortex wake patterns in superfluid4He.
Excitations in the form of quantized vortex rings are known to exist in superfluid4He at energies and momenta exceeding those of the Landau phonon-roton spectrum. They form a vortex branch of elementary excitations spectrum which is disconnected from the Landau spectrum. Interference of vortex ring excitations determines wake patterns due to uniformly traveling sources in bulk superfluid at low speeds and pressures. The dispersion law of these excitations resembles that of gravity waves on deep water with infrared wave number cutoff. As a result, vortex wake patterns featuring elements of the Kelvin ship wake are predicted. Specifically, at lowest speeds the pattern with fully developed transverse and diverging wavefronts is present. At intermediate speeds transverse wavefronts are absent within a cone whose opening angle increases with the source velocity. At largest speeds only diverging wavefronts confined within a cone whose opening angle decreases with the source velocity are found. When experimentally observed, these changes in appearance of wake patterns serve as indicators of the beginning part of the vortex branch of elementary excitations.


Robot-assisted hybrid laparoscopic Roux-en-Y gastric bypass: surgical technique and early outcomes.
Roux-en-Y gastric bypass performed laparoscopically remains the gold standard in bariatric surgery. The role of robot-assisted laparoscopic Roux-en-Y gastric bypass has not been clearly defined. We present 80 consecutive cases of robot-assisted laparoscopic Roux-en-Y gastric bypass performed at a single institution. Mechanics, early outcomes, and learning curve are evaluated. Eighty robot-assisted laparoscopic Roux-en-Y gastric bypasses were performed on 71 women and 9 men with a mean age of 39 years, mean preoperative weight of 134 kg, and mean BMI of 48. Total mean operative time was 209 minutes. There was no mortality, leak, stricture, or obstruction. Robot-assisted laparoscopic Roux-en-Y gastric bypass is a safe and feasible option for bariatric surgery. Its role in improving surgical outcomes needs to be defined further.


Influenza vaccination and warfarin anticoagulation.
Because influenza vaccine can markedly depress hepatic cytochrome P450 activity and may have caused an extreme prolongation of the prothrombin time in one patient receiving warfarin, we studied the effect of influenza vaccine on anticoagulation in 21 male outpatients receiving chronic warfarin therapy. Prothrombin times measured three to five times in the month after vaccination were in the therapeutic range as often as those measured before vaccination. Mean changes in prothrombin times measured after vaccination were not significantly different from those on the day of vaccination or in the 3 months before vaccination. The size of this study assured an 80% chance that any deviation from the observed mean prothrombin times would not exceed 2.1 s. No patient had any bleeding or thromboembolic problems. Thus, influenza vaccination of patients anticoagulated with warfarin appears to be safe.


Nonoperating room anaesthesia for elderly patients.
The number of elderly patients receiving non-operating room anaesthesia (NORA) has substantially increased because of clinical, epidemiological, social and economic reasons. Considering the high risk of anaesthesia-related adverse events in this population, along with the limitations of NORA, more specific knowledge and skills are required. Advanced age appears to be an independent risk factor for anaesthesia-related adverse events in a NORA setting, similar to the traditional operating room. As significant changes occur in the pharmacological effects of anaesthetic agents with aging, reducing dosage and carefully titrating drugs are essential. Because NORA-related injury is frequently related to airway obstruction/respiratory depression, non-invasive respiratory activity monitoring is more useful for sedation of elderly patients. Additionally, advanced age increases the risk of aspiration and cognitive complications, even during sedation. Elderly patients may greatly benefit from the lower invasiveness and faster recovery offered by interventional procedures. However, as they represent a highly heterogeneous population with large variations in physiological reserves and comorbidities, anaesthesiologists should strive to maintain the same practice standards throughout all anaesthetizing locations. Knowledge of the unique hazards associated with NORA in elderly patients may further enhance patient safety.Video abstract: NORA for elderly patients.mp4: http://links.lww.com/COAN/A66.


Binding studies and computer-aided modelling of macromolecule/odorant interactions.
Odorant-to-biopolymer (proteins and polysaccharides) binding properties influence the partition coefficients of odorant/matrix mixtures and depend on the molecular structure of the guest and the host. While air/solvent partition coefficients of odorants influence the flavor intensity of compounds in the headspace above the solvent, more complex mechanisms are proposed for the binding of a molecule to a food matrix. Odorant air/solvent partition coefficients are dependent on both the physico-chemical properties of odorant and solvent. Binding affinities for flavor compounds on various biopolymers can be estimated by calculation of physico-chemical descriptors for the odorants. Binding affinities of gamma- and delta-lactones (C7-C11) to bovine serum albumin (BSA) and beta-lactoglobulin (BLG) were investigated by ultracentrifugation and equilibrium-dialysis techniques. Quantitative structure-activity relationships (QSAR) of lactone binding on proteins (BLG and BSA) were performed by the measurement of lipophilicity and H-bond strength. Large differences in observed protein-binding properties for the various compounds clearly demonstrated that structure-activity relationship was significantly influenced by the lipophilicity of the odorant. If the structure of the receptor molecule is known, computational ligand-macromolecule docking experiments can be used to predict binding affinities for unknown compounds with the receptor molecule. A BLG-lactone binding position, not previously reported in the literature, has been identified and confirmed by competitive binding studies. A model has been developed to estimate the free energy of binding of odorants to biopolymers. Estimated free energies of binding of lactones with BLG from computational methods were in very good agreement with the experimentally obtained results.


Differential enhancement of antidepressant penetration into the brain in mice with abcb1ab (mdr1ab) P-glycoprotein gene disruption.
Mice with a genetic disruption (knockout) of the multiple drug resistance (abcb1ab) gene were used to examine the effect of the absence of the drug-transporting P-glycoprotein (P-gp) at the blood-brain barrier on the uptake of the antidepressants venlafaxine, paroxetine, mirtazapine, and doxepin and its metabolites into the brain. One hour after subcutaneous injection of venlafaxine, paroxetine, mirtazapine, or doxepin, knockout and wildtype mice were sacrificed, and the drug concentrations in brain, spleen, kidney, liver, and plasma were measured. The cerebrum concentrations of doxepin, venlafaxine, and paroxetine were higher in knockout mice, demonstrating that these substances are substrates of P-gp and that abcb1ab activity at the level of the blood-brain barrier reduces the penetration of these substances into the brain. In contrast, brain distribution of mirtazapine was indistinguishable between the groups. The differences reported here in brain penetration of antidepressant drugs that depend on the presence of the abcb1ab gene may offer an explanation for poor or nonresponse to antidepressant treatment. Furthermore, they may be able to explain in part the discrepancies between plasma levels of an antidepressant and its clinical effects and side effects.


Effects of chlorhexidine and iodine on in vitro plaques of Streptococcus mutans and Streptococcus sanguis.
Both chlorhexidine and iodine showed greater antimicrobial effect on in vitro grown S. mutans plaque than on plaque composed of S. sanguis. One treatment with iodine for 8 min inhibited the acid production of S. Mutans plaque whereas S. sanguis plaque required 20 min to be similarly affected. In contrast one treatment with chlorhexidine for up to 20 min did not completely inhibit the acid production of plaque of either microorganism. Repeated short term exposures increased the bactericidal effect of chlorhexidine but not that of iodine. The difference in antimicrobial effect between chlorhexidine and that of iodine on S. mutans and S. sanguis should be investigated in persons heavily infected by S. mutans.


Brachial artery aneurysm accompanying a homozygous methylenetetrahydrofolate reductase mutation.
Elevated plasma homocysteine (Hcy) is one of the suggested risk factors for endothelial dysfunction. There is evidence of association between raised plasma Hcy and an increased risk of developing peripheral arterial disease. A causal relationship, however, has not been established. In this report, a 37-year old male patient with the complaints of intermittent hand pain is presented. Brachial artery aneurysm accompanying a homozygous methylenetetrahydrofolate reductase mutation was detected.


Endodontic management of an impacted premolar.
This report demonstrates a simple endodontic solution to an interdisciplinary case of a patient with multiple gene deficiencies. An adolescent patient presented with an impacted premolar that could not be extracted due to high-risk conditions. A suspicious degree of radiolucency around the crown was clinically diagnosed as dentigerous cyst. The treatment dilemma and implementation are discussed. This case report offers a different treatment option for impacted teeth when significant differential diagnosis of a pericoronal lesion dictates treatment.


Initial transference of wild birds to captivity alters stress physiology.
Maintaining wild animals in captivity has long been used for conservation and research. While often suggested that captivity causes chronic stress, impacts on the underlying stress physiology are poorly understood. We used wild-caught chukar (Alectoris chukar) as a model avian species to assess how the initial 10 days of captivity alters the corticosterone (CORT) secretory pathway. In the first few days of captivity, birds lost weight, had lower hematocrit and demonstrated changes in CORT concentrations. Both baseline and restraint-stress-induced CORT concentrations decreased by days 3-5 of captivity and remained significantly lower throughout the 10 days although stress-induced concentrations began to recover by day 9. To delineate potential mechanisms underlying these CORT changes, we evaluated alterations to the hypothalamic-pituitary-adrenal (HPA) axis. Although chukar appear to be resistant to arginine vasotocin's (AVT) effects on CORT release, adrenocorticotropin hormone (ACTH) stimulated CORT release; however, ACTH stimulation did not differ during the 10 days of captivity. In contrast, negative feedback axis sensitivity, as determined by both dexamethasone suppression as well as endogenous negative feedback, decreased by day 5 but was regained by day 9. In addition, the combined stressors of capture and long distance transport eliminated the animals' ability to mount an acute CORT response on the day following the move. Therefore, introduction into captivity appeared to shift the chukar into a temporary state of chronic stress that began to recover within 9days. The duration of these alterations likely varies due to differences in capture techniques, transport distance, and species studied.


Assessing the Incidence of Symptomatic Respiratory Syncytial Virus Illness Within a Prospective Birth Cohort in Managua, Nicaragua.
Respiratory syncytial virus (RSV) causes substantial morbidity and mortality among children worldwide, commonly through acute lower respiratory tract infections (ALRI). To assess the incidence rate of symptomatic RSV illness among young children, we conducted a prospective birth cohort study following children from 0-2 years of age in Managua, Nicaragua. Children meeting the testing criteria (fever, history of fever, or severe respiratory symptoms [apnea, stridor, nasal flaring, wheezing, chest indrawing, and/or central cyanosis]) were tested for RSV infections using real-time reverse transcriptase-polymerase chain reaction. An acute lower respiratory infection was defined as a diagnosis of pneumonia, bronchiolitis, bronchitis, or bronchial hyperreactivity. The incidence rate was calculated, and 95% confidence intervals were estimated using a Poisson distribution. A total of 833 children participated in the cohort: 289 (34.7%) had at least 1 episode of laboratory-confirmed RSV, and 156 (18.7%) of had an episode of RSV-associated ALRI (RSV-ALRI). The incidence rate of symptomatic RSV was 248.1 cases per 1000 person-years (95% confidence interval [CI] 223.2-275.7). While infants aged 6-11 months had the highest incidence of symptomatic RSV (361.3/1000 person-years, 95% CI 304.4-428.8), infants <3 months had the highest incidence of severe RSV (RSV-associated hospitalizations and/or severe ALRI). RSV was also associated with 25.0-37.5% of deaths from medical causes (n = 8). A substantial burden of RSV exists among children aged <2 years in Nicaraguan communities. RSV was also a leading cause of infant mortality among study participants. The development and implementation of effective RSV prevention and treatment measures represent an opportunity to substantially reduce severe illness and death among children worldwide.


Simultaneous determination of plasma retinol, alpha-tocopherol, lycopene, alpha-carotene, and beta-carotene by high-performance liquid chromatography.
Reverse-phase high-performance liquid chromatography was used for the simultaneous determination of retinol, alpha-tocopherol, lycopene, alpha-carotene, and beta-carotene in human plasma. A multiple solvent system of methanol followed by a mixture of methanol:acetonitrile:chloroform (47:42:11) provided clear separation of these compounds. With retinyl acetate as an internal standard, standard curves were developed for each compound on the basis of peak area ratios. The coefficient of variation was less than 10% in all cases within a run. Between-run reproducibility was within +/- 2 standard deviations. The method required 100 to 200 microliter of plasma and 16 min of elution time per sample. Stability studies showed plasma samples could be stored at -10 degrees C with occasional freeze-thaw cycles for 3 to 5 weeks. This method should prove useful in clinical and epidemiological work.


Some aspects about time broadening in fluorescence up-conversion measurements.
Several aspects contributing to the temporal broadening in the measurement of ultrafast fluorescence by means of up-conversion wave mixing are presented: the characteristics of the sample, those of the collection optics, and the wave mixing with the gate pulse in a non-linear crystal. It is concluded that these contributions are emission wavelength dependent and can be as important as the pulse durations in determining the instrument response function in this technique.


The role of direct single monetary grants in residents' choice of field of residency.
In an attempt to address severe medical manpower shortages in several medical disciplines, the Israeli Ministry of Health offered grants to residents who chose one of these fields. A total of 220 residents from various disciplines were surveyed on demographic, academic, and professional data, and asked to rank considerations in the choice of their field of residency. Residents in targeted fields attributed significantly more importance to the grant in their decision-making process (U = 3704.5, p < 0.001). This effect remained significant in a multivariate model (OR 1.67, 95%CI 1.32-2.10, p < 0.001). Higher age (OR 1.15, 95%CI 1.01-1.31, p = 0.031) and attribution of significance to the working conditions compared to other residency fields (OR 1.69, 95%CI 1.23-2.32, p = 0.001) were significantly associated with receptivity toward the grant in a multivariate analysis. Receptivity toward the offered grants correlated with real-life data shows a rise in physician in these fields, and the weak association between such receptivity and most variables tested may suggest that the grants were perceived as a property of the specific choice rather than a special bonus. Grants may be useful in diverting medical manpower. Further analysis and modeling are required to determine causal relationship and budgetary feasibility.


[Genome wide screening and characterization of long non-coding RNAs in esophageal cancer].
To screen for esophageal squamous cell carcinoma (ESCC)-associated long non-coding RNAs (lncRNA) and identify oncogenic lncRNA contributing to ESCC pathogenesis. A lncRNA array containing 7419 lncRNA was used to detect the transcriptional profiles of lncRNA of four pairs of ESCC and matched normal esophageal tissue. Bioinformatic analysis was employed to identify differentially expressed ESCC associated lncRNA (ESCCAL). Quantitative real-time PCR was used to verify selected dysregulated lncRNA on independent ESCC samples. Genome-wide transcriptome profiling (coding and or noncoding RNA transcripts) was able to distinguish ESCC from normal tissue. Among these, bioinformatic analysis has identified 154 differentially expressed ESCC associated lncRNA (ESCCALs), which included 111 downregulated and 43 upregulated lncRNA in ESCC relative to the normal tissue (P< 0.01). The highest upregulated lncRNA (ESCCAL_1) and known onco-lncRNA HOTAIR was further verified in 26 paired ESCC samples. ESCCAL_1 and HOTAIR were found to be highly expressed in 17 ESCC and 18 ESCC compared with normal esophageal tissues. This investigation has revealed large scale aberrant expression of lncRNA in ESCC. About 70% of novel lncRNA-ESCCAL_1, together with a known lncRNA-HOTAIR, are highly expressed in ESSC, suggesting that ESCCAL_1 and HOTAIR may participate in the pathological process of ESCC. Furthermore, lncRNA could be potential diagnostic and prognostic biomarkers for ESCC.


Surface Modification of Boron-Doped Diamond with Microcrystalline Copper Phthalocyanine: Oxygen Reduction Catalysis.
Surface modification of boron-doped diamond (BDD) with copper phthalocyanine was achieved using a simple and convenient dropcast deposition, giving rise to a microcrystalline structure. Both unmodified and modified BDD electrodes of different surface terminations (namely hydrogen and oxygen) were compared via the electrochemical reduction of oxygen in aqueous solution. A significant lowering of the cathodic overpotential by about 500 mV was observed after modification of hydrogen-terminated (hydrophobic) diamond, while no voltammetric peak was seen on modified oxidised (hydrophilic) diamond, signifying greater interaction between copper phthalocyanine and the hydrogen-terminated BDD. Oxygen reduction was found to undergo a two-electron process on the modified hydrogen-terminated diamond, which was shown to be also active for the reduction of hydrogen peroxide. The lack of a further conversion of the peroxide was attributed to its rapid diffusion away from the triple phase boundary at which the reaction is expected to exclusively occur.


Corporate political activity of the dairy industry in France: an analysis of publicly available information.
In the present study, we used a structured approach based on publicly available information to identify the corporate political activity (CPA) strategies of three major actors in the dairy industry in France. We collected publicly available information from the industry, government and other sources over a 6-month period, from March to August 2015. Data collection and analysis were informed by an existing framework for classifying the CPA of the food industry. Setting/Subjects Our study included three major actors in the dairy industry in France: Danone, Lactalis and the Centre National Interprofessionnel de l'Economie Laitière (CNIEL), a trade association. During the period of data collection, the dairy industry employed CPA practices on numerous occasions by using three strategies: the 'information and messaging', the 'constituency building' and the 'policy substitution' strategies. The most common practice was the shaping of evidence in ways that suited the industry. The industry also sought involvement in the community, establishing relationships with public health professionals, academics and the government. Our study shows that the dairy industry used several CPA practices, even during periods when there was no specific policy debate on the role of dairy products in dietary guidelines. The information provided here could inform public health advocates and policy makers and help them ensure that commercial interests of industry do not impede public health policies and programmes.


Temporal discrepancies between low and high frequency vibrations of the second heart sound.
The morphologic analysis of the second heart sound may provide some useful informations, not enough debated in the literature, concerning the functional status of cardiac patients. We noticed significant temporal discrepancies on the phonocardiographic tracings between the onset of the second heart sound in the lowest and in the highest frequency ranges. The correlations between the highest and the lowest frequency vibrations of the second heart sound were analysed in 119 controls, without overt cardiovascular disease, aged from 20 to 40 years and 50 to 70 years and in 148 patients with old myocardial infarction aged 42 to 80 years. The lowest frequency vibrations of the second heart sound appeared earlier in healthy young subjects than in middle-aged people. These differences may be explained by the reduced aortic compliance with advanced age. The incidence of early beginning of the low frequency vibrations of the second heart sound is greater in patients with old myocardial infarction and a poor myocardial contractile condition than in controls of about the same age. This difference may be due to impaired ventricular relaxation.


Factors influencing functional outcome of proximal interphalangeal joint collateral ligament injury when treated with buddy strapping and exercise.
Prospective cohort. This study evaluates the factors influencing treatment outcomes of proximal interphalangeal (PIP) joint collateral ligament injuries when treated with buddy strapping. Sixty-seven patients treated with buddy strapping for a PIP joint injury were enrolled. The finger range of motion (ROM), grip strength, and a Quick Disability of the Arm, Shoulder, and Hand (QuickDASH) score were assessed at 3 and 6 months after the initial injury. The factors that were assessed for their influence on the functional outcomes included age, sex, hand dominance, affected finger, type of injury, injury severity, time to treatment, the duration of buddy strapping, and exercise training. Buddy strapping for PIP joint injuries led to satisfactory results with 77% recovery of grip strength, 84% recovery in ROM, and mean QuickDASH scores of 14 at 6 months. A decrease in grip strength was associated with an increase in age and injury severity at 6 months, and these 2 factors accounted for 22% of the variance in the grip strength. A decrease in ROM was associated with the delayed treatment, which accounted for 18% of the variance in ROM at 6 months. An increased disability was associated with delayed treatment, female gender, and radial digit injury at 3 months, and these 3 factors accounted for 37% of the variance in disability. At 6 months, only the delayed treatment remained an associated factor, which accounted for 20% variance in disability. PIP collateral ligament injuries had very good outcomes with buddy strapping. However, delayed treatment was significantly associated with poor functional outcomes in terms of the ROM and disability. An increase in age and injury severity were associated with lower grip strength up to 6 months, whereas a female gender and radial digit injury were associated with an increased disability up to 3 months. 2.


Improvement of physical performance by transcutaneous nerve stimulation in athletes.
The present pilot study tested the exercise response to transcutaneous nerve stimulation (TNS) of 21 volunteers, who were well-trained competitive athletes. In 62 experiments (n) they received low-frequency TNS (2 Hz) for 30-45 min prior to either a road or track race, swimming race, bicycle ergometer exercise, isometric muscular endurance test, or dynamometer hand grip test. Improvement in performance compared with a corresponding number of control tests, without TNS or with placebo stimulation in the same subjects, was almost regularly observed in running, swimming and ergometer cycling, although with great individual variations. The average improvement was 4.3 sec (2.2%) in 1.000 m road racing (n = 9); 2.3 sec (1.8%) in 800 m track racing (n = 5); 0.9 sec (1.4%) in 100 m swimming (n = 12); 1.3 sec (0.8%) in 200 m swimming (n = 6); and 2.5 sec (0.9%) in 400 m swimming (n = 3). In a bicycle ergometer test with stepwise, progressive exercise to muscular fatigue, the maximal capacity was increased by 9% (n = 4). Local isometric muscle endurance of the elbow flexors (n = 7) and hand grip strengths (n = 11) were not significantly altered. Possible mechanisms involved in the response to TNS are discussed.


The Danish national multicenter schizophrenia project: assessment of psychotic patients for dynamic psychotherapy (APPP).
Clinicians need guidance in selecting schizophrenic patients for individual psychodynamic psychotherapy. The purpose of the present study was to investigate whether a 17-item questionnaire (APPP) for quantification of suitability for psychotherapy could predict continuance, adherence and outcome from individual dynamic psychotherapy with patients with schizophrenic psychoses. Therapists rated 72 first-episode patients with schizophrenic psychoses in the initial interview. The scores were then correlated to the course of therapy and change in symptoms. APPP was tested to have good psychometric characteristics and had a satisfactory interrater reliability ((ICC,2)=0.70), when four raters scored eight videotaped interviews with eight different patients. The scale scores were highly correlated to "therapeutic alliance" measured by the Working Alliance Inventory (WAI) and the Active Engagement Scale (AES). APPP suitability gave a good early prediction of adherence to therapy (continued in therapy at least 12 months and a satisfactory number of sessions), but had no predictive value of symptomatic improvement or improved social function after 1 year.


Targeting Driver Oncogenes and Other Public Neoantigens Using T Cell Receptor-Based Cellular Therapy.
T cell reactivity to tumor-specific neoantigens can drive endogenous and therapeutically induced antitumor immunity. However, most tumor-specific neoantigens are unique to each patient (private) and targeting them requires personalized therapy. A smaller subset of neoantigens includes epitopes that span recurrent mutation hotspots, translocations, or gene fusions in oncogenic drivers and tumor suppressors, as well as epitopes that arise from viral oncogenic proteins. Such antigens are likely to be shared across patients (public), uniformly expressed within a tumor, and required for cancer cell survival and fitness. Although a limited number of these public neoantigens are naturally immunogenic, recent studies affirm their clinical utility. In this review, we highlight efforts to target mutant KRAS, mutant p53, and epitopes derived from oncogenic viruses using T cells engineered with off-the-shelf T cell receptors. We also discuss the challenges and strategies to achieving more effective T cell therapies, particularly in the context of solid tumors.


[Multimodality treatment for colorectal cancer].
Preoperative radiochemotherapy has clear advantages compared to postoperative therapy in rectal carcinoma of UICC stages II and III, and is indicated according to current guidelines. However, it does not reduce the rate of distant metastases. There is therefore a clear need to improve pre- and postoperative systemic treatment, in order to improve survival times. New combination chemotherapy regimens (5-FU/FS + oxaliplatin as well as XELOX) are being tested both pre and postoperatively, in some cases in combination with antibodies (bevacizumab or cetuximab). Instead of conventional neoadjuvant radiotherapy (50.4 Gy over 5-6 weeks), which is combined with neoadjuvant chemotherapy, preoperative short-term radiotherapy (5 x 5 Gy in 5 days) can be used. The advantages and disadvantages must be weighed up on an individual basis until results of the Berlin trial are available.


Regeneration of hair and other skin appendages: A microenvironment-centric view.
Advances in skin regeneration have resulted in techniques and products that have allowed regeneration of both the dermis and epidermis. Yet complete skin regeneration requires the adnexal skin structures. Thus it is crucial to understand the regenerative potential of hair follicles where genetic, nutritional, and hormonal influences have important effects and are critical for skin regeneration. The follicular stem cell niche serves as an anatomical compartment, a structural unit, a functional integrator, and a dynamic regulator necessary to sustain internal homeostasis and respond to outside stimuli. In particular, mechanics such as pressure, compression, friction, traction, stretch, shear, and mechanical wounding can influence hair loss or growth. Relevant niche signaling pathways such as Wnt, bone morphogenetic protein, fibroblast growth factor, Shh, and Notch may yield potential targets for therapeutic interventions.


Bioconversion of artemisinin to its nonperoxidic derivative deoxyartemisinin through suspension cultures of Withania somnifera Dunal.
Biotransformation of artemisinin was investigated with two different cell lines of suspension cultures of Withania somnifera. Both cell lines exhibited potential to transform artemisinin into its nonperoxidic analogue, deoxyartemisinin, by eliminating the peroxo bridge of artemisinin. The enzyme involved in the reaction is assumed to be artemisinin peroxidase, and its activity in extracts of W. somnifera leaves was detected. Thus, the non-native cell-free extract of W. somnifera and suspension culture-mediated bioconversion can be a promising tool for further manipulation of pharmaceutical compounds.