FCRL3 gene polymorphisms contribute to the radiographic severity rather than susceptibility of rheumatoid arthritis.
The ethnic heterogeneity and genetic complexity of rheumatoid arthritis (RA) have produced inconsistent results in previous genetic association studies concerning FCRL3. This study sought to delineate the association between the FCRL3 gene polymorphisms and susceptibility to RA and to investigate the effects of the polymorphisms on the progression of joint destruction in RA. RA patients (n = 377) and healthy unrelated controls (n = 298) were recruited. Genotyping of -169 T>C and -110 G>A in the promoter and 1,381 G>A in the intron was accomplished using FRET assays. The distribution of genotypes and haplotypes did not differ between RA patients and controls. When we investigated the role of FCRL3 polymorphisms for the severity of RA, patients with the CC genotype in the -169 T>C polymorphism had a higher modified Sharp score than other genotype groups (p = 0.034) among patients with disease duration ≥10 years. The slope of the regression line for modified Sharp score over disease duration (10.12/year) was significantly steeper in patients with the CC genotype than in the T carriers (5.69/year) at the -169 T>C polymorphism (p = 0.003), indicating the faster progression of radiologic destruction in the CC genotype. In conclusion, polymorphisms of the FCRL3 gene may contribute to the progression of joint destruction rather than susceptibility of RA.


Patterns of Recurrence in Appendix Cancer After Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy.
It is thought that low-grade (LG) appendiceal cancer (AC) demonstrates predominantly intraperitoneal recurrence (IPR) after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), whereas high-grade (HG) tumors progress both intra- and extraperitoneally (EPR). However, evidence supporting this conception is lacking; therefore, we assessed recurrence in various AC histologies. A retrospective, cohort study was conducted by using a single-center database (1998-2022). Recurrence patterns (IPR, EPR, combined) were identified for LG, HG, high-grade with signet ring cells (SRC), and goblet cell carcinoma (GCC). We included 432 complete (CC-0/1) CRS/HIPECs: 200 LG, 114 HG, 72 SRC, and 46 GCC. Median follow-up was 78 (95% confidence interval [CI] 70-86) months. Overall, 34% (n = 148) of patients recurred. IPR was the most common (LG 16%, HG 27%, SRC 36%, GCC 26%) with median time to recurrence (MTR) of 21 (IQR: 12-40) months. EPR (liver, lung, pleura, lymph nodes, or bones) occurred in LG 3%, HG 9%, SRC 22%, and GCC 7%. MTR was 11 (IQR: 4-16) months. Combined pattern occurred in LG 0%, HG 8%, SRC 7%, and GCC 0%. MTR was 13 (IQR: 7-18) months. Iterative surgery was performed in 53% IPR, 18% EPR, and 51% combined. Median post-recurrence survival was longer after IPR compared with EPR and combined recurrence: 36 (95% CI 25-47) versus 13 (95% CI 7-19) and 18 (95% CI 6-30) months (p < 0.01). After complete CRS/HIPEC, IPR was the predominant pattern in all AC histologies and occurred later. Post-recurrence survival after IPR was longer. Knowing AC recurrence patterns can help to understand its biology and plan follow-up and post-relapse management.


Bias from depletion of susceptibles: the example of hormone replacement therapy and the risk of venous thromboembolism.
The data on the association between hormone replacement therapy and the increased risk of venous thromboembolism (VTE) in postmenopausal women are conflicting. The observed differences between oral estrogen and oral estrogen-progestogen combination formulations may be the result of bias from depletion of susceptibles. We used United Kingdom's Clinical Practice Research Datalink to identify the cohort of all women aged 50 to 79 during 1987-2008, with all incident cases of VTE occurring during the study period identified. Using a nested case-control approach, the rate ratios (RRs) of VTE with current use of oral estrogen and oral estrogen-progestogen combinations were estimated as a function of duration of use using conditional logistic regression with cubic splines. The cohort of 955 582 postmenopausal women included 23 505 cases of VTE matched to 231 562 controls. The risk of VTE was increased with current use of oral estrogen (RR 1.49; 95% confidence interval: 1.37 to 1.63) and oral estrogen-progestogen (RR 1.54; 95% confidence interval: 1.44 to 1.65), relative to non-use. When assessed by duration of use, the risks with oral formulations were particularly elevated during the first year of use and were reduced subsequently. The phenomenon of depletion of susceptibles should be considered in cohort studies evaluating acute side effects of medications. This can be achieved by estimating the risk as a function not only of current use but also of duration of use. Copyright © 2017 John Wiley & Sons, Ltd.


Morphological and behavioral antipredatory adaptations of decapod zoeae.
Zoeae of some species of estuarine decapods are retained in the estuary throughout development while others are exported into nearshore coastal waters. The horizontal migrations of decapod zoeae to coastal waters may have evolved to reduce the probability of encountering planktivorous fishes which are most abundant in the estuary. If so, then the morphological vulnerability of zoeae to fish predation should be inversely related to the number of predators occurring where they develop. Six species of estuarine decapod zoeae were offered to Menidia menidia and Fundulus heteroclitus. The behavioral interactions were observed to determine the prey's vulnerability to predation, and the mode of operation and relative effectiveness of their defenses. Feeding trials and behavioral observations both demonstrated that M. menidia 6-16 mm long preferred Uca minax and Callinectes sapidus zoeae, which are exported from the estuary, to Rhithropanopeus harrisii, Sesarma reticulatum and Palaemonetes pugio, which are retained within estuaries. Pinnotheres ostreum zoeae develop in the lower estuary and fish demonstrated an intermediate preference for the zoeae. Menidia menidia 20-40 mm long showed similar preferences for R. harrisii S. reticulatum, P. ostreum and U. minax as did small silversides. Large-mouthed demersal fish, Fundulus heteroclitus 6-10 mm long, also preferred U. minax to R. harrisii, but more readily preyed on zoeae than did M. menidia. The exported species of zoeae have shorter spines and smaller bodies than do retained zoeae, except P. ostreum which is small, spineless and passively sinks when attacked by fish. Other retained species of zoeae also have postcontact behavioral defenses which enhance the effectiveness of their morphological defenses. Zoeae do not evade attacks by fishes, but fishes quickly learned to avoid zoeae, which increases the effectiveness of the zoeae's antipredatory adaptations.


Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation.
Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.


CXCR7 agonists inhibit the function of CXCL12 by down-regulation of CXCR4.
The CXCL12/CXCR4 axis is involved in many cellular responses for host homeostasis, and malfunction of this signaling pathway is associated with a variety of diseases. It is now known that CXCL12 also binds to another newly identified chemokine receptor, CXCR7, which does not couple with a G-protein. CXCR7 can form homodimers, or heterodimers with CXCR4, and is believed to sequester the chemokine CXCL12, although the CXCL12/CXCR7 axis activates MAP kinases through β-arrestin. Therefore, it has not been well defined how CXCR7 activation affects CXCL12-induced cellular events. To elucidate the function of CXCR7, we prepared CXCR7 agonist Compound 1. Compound 1 is a selective and potent CXCR7 agonist that clearly has the activity to recruit β-arrestin toward CXCR7. It also activates MAP kinases Akt and ERK. Using this compound, we confirmed that the CXCR7 agonist, but not an antagonistic antibody, did inhibit CXCL12 induced HUVEC tube formation, suggesting that activation of CXCR7 ameliorates CXCL12 induced cellular events, probably by affecting on CXCR4 function. We show that β-arrestin recruitment to CXCR4 is reduced by over-expression of CXCR7 and activation of CXCR7 by agonist treatment reduces the protein level of CXCR4. Based on our results, together with reported information, we propose that CXCR7, when up-regulated upon inflammation, can act as a negative regulator of CXCR4 by heterodimerizing with CXCR4, inducing its internalization and degradation. This mechanism suggests that CXCR7 agonists can have a therapeutic effect on CXCL12 causing diseases by countering the effects of CXCL12.


Dermal echogenicity: a biological indicator of individual cumulative UVR exposure?
Dermal alterations due to chronic UVR exposure may influence dermal ultrasound echogenicity, and a subepidermal low-echogenic band has been proposed as a marker of photoaging. The aim of this study was to determine whether dermal echogenicity could be used as a biological UVR dosimeter. We included 201 subjects (138 healthy volunteers, 31 patients with basal cell carcinoma, and 32 patients with cutaneous malignant melanoma). The number of low-echogenic pixels in the upper dermis relative to the lower dermis (LEP(u/l)) was determined in sun-exposed and sun-protected skin. Individual UVR exposure data were collected retrospectively and prospectively using a questionnaire and electronic personal UVR dosimeters. Age, but not sex, skin type, constitutive pigmentation or smoking, correlated significantly with LEP(u/l) at all body sites. Different measures of individual UVR exposure were significantly positively correlated with LEP(u/l) (together r(2)=0.39, dorsal forearm), but separately the correlations were poor ( r(2)=0.04-0.19). LEP(u/l) was higher in the dorsal forearm in a group with high UVR exposure compared to a low-exposure group ( P=0.007). Skin cancer patients in general had a lower LEP(u/l) than healthy subjects. The results indicate that the age-related increase in LEP(u/l) might be attributed mainly to UVR exposure, and that the methods used to obtain the UVR exposure data might not be sufficiently sensitive or specific. Genetic factors might also influence LEP(u/l). We consider LEP(u/l) to be a sensitive and specific marker for UVR exposure at the dorsal aspect of the forearm in healthy subjects.


Adaptation and optimization of the emulsification-diffusion technique to prepare lipidic nanospheres.
In this study, the emulsification-diffusion method traditionally used to prepare polymeric nanoparticles was adapted to obtain lipidic nanospheres (LN) using four model lipids. The method consists of dissolving the lipid in a partially water-miscible solvent (previously saturated with water) at room temperature or at controlled temperature depending on lipid solubility. This organic phase is emulsified in an aqueous solution of a stabilizing agent (saturated with solvent) by conventional stirring at the same temperature used to dissolve the lipid. This oil-in-water emulsion is then diluted with an excess of water at controlled temperature in order to provoke the diffusion from the internal phase into the external phase thereby causing lipid aggregation in the form of LN. This new approach for the preparation of LN has clear advantages over the existing methods, namely: (i) it is efficient and versatile; (ii) easy implementation and scaling up (with no need of high energy sources); (iii) high reproducibility and narrow size distribution; (iv) less physical stress (i.e., long exposure to high temperatures and to mechanical dispersion); (v) it is not necessary to dissolve the drug in the melted lipid. The selection of the water-miscible solvent and the stabilizers are critical parameters to obtain lipidic particles in the nanometric range. In general, solvents with high water miscibility and stabilizers able to form stable emulsions are preferred. The results demonstrated that it was possible to reduce the particle size by increasing the process temperature, the stirring rate, the amount of stabilizer, and by lowering the amount of lipid. Control of the preparative variables allowed to obtain LN with diameters under 100 nm. It was found that the influence of preparative parameters was associated with a mechanism based on a physicochemical instability. In this sense, it is suggested that the rapid solvent diffusion produces regions of local supersaturation near the interface, and LN are formed due to the ensuing interfacial phase transformations and lipid aggregation that occur in these interfacial domains. In terms of stability, only poly(vinyl alcohol) (PVAL) was able to preserve the physical stability of the dispersion for long periods after preparation. This effect was attributed to the ability of PVAL chains to form a strongly attached layer on the nanoparticle surface with an excellent repulsion effect.


The "Wall of Fear": the bridge between the traumatic event and trauma resolution therapy for childhood sexual abuse survivors.
A multitude of published books and papers on child sexual abuse (CSA) describe symptoms, long-term effects, and therapy for survivors of abuse. However, the parallels between the nature of the sexual trauma event(s) as originally experienced by the victim and the therapeutic process into which the survivor later becomes engaged have not been reported. This paper attempts to fill that gap and proposes that the concept of a Wall of Fear is the bridge connecting the two. In the first part of the paper, a model of the CSA experience based upon Furniss (1991) will be explained in order to point out the basis for the dissociation and other symptomatology demonstrated by the CSA victim. Following that, the stages of therapy will be mapped out, with special attention to the concept of the Wall of Fear (Oz, 1999) and traumatic memory resolution (abreactions) and with reference to the experience of the original traumatic events. Therapist fear of decompensation will be addressed.


Dogfish hair cells sense hydrostatic pressure.
Many marine invertebrates and fish respond to hydrostatic pressure in order to regulate their depth and synchronize their behaviour to tidal cycles. Here we investigate the effect of hydrostatic pressure on the vestibular hair cells located in the labyrinth of the dogfish Scyliorhinus canicula, and find that it modulates their spontaneous activity and response to angular acceleration. This may explain not only the low resting activity of vertebrate hair cells but also how fish that do not have swim bladders can sense hydrostatic cues.


Phototransformation of polychlorinated dibenzo-p-dioxins from photolysis of pentachlorophenol on soils surface.
The phototransformation of polychlorinated dibenzo-p-dioxins (PCDDs) by photolysis of pentachlorophenol (PCP) on soil surface under irradiation of UV light in the laboratory has been investigated. Octachlorodibenzo-p-dioxin (OCDD) and heptachlorodibenzo-p-dioxin (H7CDD) were detected from the products of the photoreactions. The effects of soil types with different basic soil physicochemical properties were varied from silt loam, silt clay and clay soil on the formation of PCDDs by irradiation of PCP on soils surface. Fulvic acids can prevent phototransformation of PCDDs by photolysis of PCP on soil surface.


Understanding technology adoption in clinical care: clinician adoption behavior of a point-of-care reminder system.
Evaluation studies of clinical decision support systems (CDSS) have tended to focus on assessments of system quality and clinical performance in a laboratory setting. Relatively few studies have used field trials to determine if CDSS are likely to be used in routine clinical settings and whether reminders generated are likely to be acted upon by end-users. Moreover, such studies when performed tend not to identify distinct user groups, nor to classify user feedback. To assess medical residents' acceptance and adoption of a clinical reminder system for chronic disease and preventive care management and to use expressed preferences for system attributes and functionality as a basis for system re-engineering. Longitudinal, correlational study using a novel developmental trajectory analysis (DTA) statistical method, followed by a qualitative analysis based on user satisfaction surveys and field interviews. An ambulatory primary care clinic of an urban teaching hospital offering comprehensive healthcare services. 41 medical residents used a CDSS over 10 months in their daily practice. Use of this system was strongly recommended but not mandatory. A group-based, semi-parametric statistical modeling method to identify distinct groups, with distinct usage trajectories, followed by qualitative instruments of usability and satisfaction surveys and structured interviews to validate insights derived from usage trajectories. Quantitative analysis delineates three types of user adoption behavior: "light", "moderate" and "heavy" usage. Qualitative analysis reveals that clinicians of distinct types tend to exhibit views of the system consistent with their demonstrated adoption behavior. Drawbacks in the design of the CDSS identified by users of all types (in different ways) motivate a redesign based on current physician workflows. We conclude that this mixed methodology has considerable promise to provide new insights into system usability and adoption issues that may benefit clinical decision support systems as well as information systems more generally.


Wiretap laws and the perioperative physician - The current state of affairs.
Wiretapping laws generally govern the legality of surreptitious or unconsented audio recording or other interception of face-to-face conversations, telephone calls, and other oral or wire communications. Many of these laws were originally passed in the late 1960s or 70s, and many have since been modified or amended. Wiretap laws vary from state to state within the United States, and many clinicians as well as patients are often unaware of the scope and implications of these laws. We provide three hypothetical case examples to illustrate scenarios in which wiretapping laws come into play. Through a review of current legislation, we compiled relevant wiretapping statutes for each state, as well as the potential civil remedies and criminal punishments that could be imposed for violations. We include the results of targeted research related to cases in which rights or claims under applicable wiretap statues have been asserted in the context of medical encounters and healthcare practice. We classified thirty-seven out of 50 states (74%) as one-party consent state laws, nine out of 50 states (18%) as all-party consent state laws, and the remaining four states (8%) as "Mixed". Remedies and punishments for violations of state wiretapping laws generally can involve civil or criminal fines and/or potential incarceration. Cases in which healthcare practitioners have asserted rights under wiretap laws remain rare. Our findings demonstrate heterogeneity with regard to the wiretapping laws state-to-state. The majority of punishments for violations involve fines and/or potential incarceration. Given the wide variability in state legislature, we suggest that anesthesiologists know their state's wiretapping law.


Trait-related neural basis of attentional bias to emotions: a tDCS study.
Negative emotional stimuli can strongly bias attention, particularly in individuals with high levels of dispositional negative affect (NA). The current study investigated whether the prefrontal cortex (PFC), a brain region involved in the top-down regulation of emotional processing, plays a different role in controlling attention to emotions, depending on the individual NA. Sham and anodal transcranial direct current stimulation (tDCS) was delivered over the right or left PFC while assessing attentional bias (AB) to emotions (happy, angry, sad faces) in individuals with higher and lower trait NA. When tDCS was inactive (sham), individuals with higher trait NA showed AB toward angry and away from sad faces, while individuals with lower trait NA presented with no AB. Right anodal-tDCS abolished the AB toward angry faces and induced an AB toward sad faces in individuals with higher trait NA, while no effect was found in individuals with lower trait NA. Left anodal-tDCS abolished any AB in individuals with higher trait NA and induced an AB away from happy faces in individuals with lower trait NA. These findings confirm a critical role of trait NA in AB to emotions and demonstrate a different involvement of PFC in emotional processing based on dispositional affect.


Pyrogenic immunomodulators increase the level of prostaglandin E2 in the blood simultaneously with the onset of fever.
Blood prostaglandin E2 (PGE2) levels, estimated by radioimmunoassay, and body temperatures of conscious rabbits were measured simultaneously during fever in response to polyinosinic: polycytidylic acid, lipopolysaccharide and interleukin 1/endogenous pyrogen. The effects of the antipyretic agent ketoprofen on both parameters was also studied. Significant rises (in the order of 6- to 8-fold) in the PGE2 level were observed after injection of either of the three pyrogens and occurred simultaneously with the rise in temperature. Ketoprofen given after the onset of fever in response to the pyrogens produced an immediate defervescence and a simultaneous decrease in plasma PGE2. Ketoprofen given before the pyrogens prevented any rise in either body temperature or plasma PGE2 level. When animals were subjected to an environmental temperature of 34 degrees C a hyperthermia was observed without any change in the blood PGE2 level. These results suggest that an increase in the blood PGE2 level may contribute to the pathogenesis of fever.


Synthesis of radioiodine labeled dibenzyl disulfide for evaluation of tumor cell uptake.
Benzyl 4-halobenzyl and ally benzyl disulfide were synthesized as diallyl disulfide analogues and their tumor growth inhibitory effects on the cancer cells (SNU C5 and MCF-7) were comparable to that of diallyl disulfide, indicating that the disulfide functional group was responsible for the tumor growth inhibitory effects. Cu(I)-assisted radioiodination of benzyl 4-bromobenzyl disulfide gave benzyl 4-[123I/125I]iodobenzyl disulfide in 30-40% radiochemical yield. The radiolabeled disulfide was taken up by the cancer cells in a time-dependent manner, and the uptake was inhibited by the pretreatment of S-methyl methanethiosulfonate (MMTS), phorone and diallyl disulfide. This study suggested that the radiolabeled dibenzyl disulfide was taken up by the cancer cells via thiol-disulfide exchange and retained inside the cells.


12 S small nuclear ribonucleoprotein-associated acidic-and pyrimidine-specific endoribonuclease from calf thymus and L5178y cells.
12 S ribonucleoprotein (RNP) particles were separated from a 45 S RNP complex (Bachmann, M., Zahn, R. K. and Müller, W. E. G. (1983) J. Biol. Chem. 258, 7033-7040) isolated from calf thymus and L5178y cells. The particles were determined to be associated with an acidic endoribonuclease (pI 4.1; pH optimum 6.2). the enzyme requires Mg2+ and is sensitively inhibited by higher NaCl concentrations. The nuclease specifically degrades poly(U) and poly(C) in an endonucleolytic manner; the end-products are 3'-UMP (85%) and 2',3'-cyclic UMP (12%). Poly(A) strongly inhibits the pI 4.1 endoribonuclease activity. The Michaelis constant (for poly(U)) was determined as 82 microM and the maximal reaction velocity was 0.54 mumol/microgram per h. The endoribonuclease is distinguished from the known pyrimidine-specific ribonucleases (pancreatic ribonuclease and endoribonuclease VII) by further criteria, e.g., resistance to thiol reagents, inhibition by EDTA, Mg2+ requirement, pI and pH optimum. Using the techniques of counterimmunoelectrophoresis and immunoaffinity column chromatography it was shown that the pI 4.1 endoribonuclease-associated 12 S RNP particles display antigenicity to anti-Sm and anti-(U1)-RNP antibodies. An RNA component, isolated from the 12 S-45 S hypercomplex, was identified as U1-snRNA.


Phase I first-in-human study of TAK-285, a novel investigational dual HER2/EGFR inhibitor, in cancer patients.
This phase I first-in-human study was conducted in Japanese patients to investigate the safety, pharmacokinetics (PKs), and determine the maximum tolerated dose (MTD) of oral TAK-285, a novel dual erbB protein kinase inhibitor that specifically targets human epidermal growth factor receptor (EGFR) and HER2. The TAK-285 dose was escalated until MTD was determined. A second patient cohort received TAK-285 at the MTD for at least 4 weeks. In all, 26 patients received TAK-285 at doses ranging from 50 to 400 mg once daily (q.d.) or twice daily (b.i.d.); 20 patients made up the dose escalation cohort and the remaining 6 patients were the repeated administration cohort. TAK-285 was well tolerated. Dose-limiting toxicities noted in two patients who received 400 mg b.i.d. were grade 3 increases in aminotransferases and grade 3 decreased appetite. Consequently, the MTD was determined to be 300 mg b.i.d. Absorption of TAK-285 was rapid after oral dosing, and plasma exposure at steady-state increased in a dose-proportional fashion for doses ranging from 50 to 300 mg b.i.d. A partial response was observed for one patient with parotid cancer who received 300 mg b.i.d. The toxicity profile and PK properties of oral TAK-285 warrant further evaluation.


Structure and sensory equipment of the ovipositor of Habrobracon hebetor (Say) (Hymenoptera: Braconidae).
The microsculpture of various structures of the ovipositor of Habrobracon hebetor (Say) (Hymenoptera: Braconidae) is described from scanning and transmission electron microscopy. These include: the ovipositor egg canal, valvillus, seal of the first valvulae, interlocking mechanism (olistheter) connecting the first and second valvulae, an olistheter-like interlocking mechanism connecting the two pieces of the first valvulae, annulation, microtrichia of the third valvulae, and the ovipositor sensory equipment. Better understanding of the microsculpture of these components may make their roles in stinging, oviposition, and the host selection process more clear.


The 30 S lobster skeletal muscle Ca2+ release channel (ryanodine receptor) has functional properties distinct from the mammalian channel proteins.
The 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (Chaps)-solubilized ryanodine receptor (RyR) of lobster skeletal muscle has been isolated by rate density centrifugation as a 30 S protein complex. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of the purified 30 S receptor revealed a single high molecular weight protein band with a mobility intermediate between those of the mammalian skeletal and cardiac M(r) 565,000 RyR polypeptides. Immunoblot analysis showed no or only minimal cross-reactivity with the rabbit skeletal and canine cardiac RyR polypeptides. By immunofluorescence the lobster RyR was localized to the junctions of the A-I bands. Following planar lipid bilayer reconstitution of the purified 30 S lobster RyR, single channel K+ and Ca2+ currents were observed which were modified by ryanodine and optimally activated by millimolar concentrations of cis (cytoplasmic) Ca2+. Vesicle-45Ca2+ flux measurements also indicated an optimal activation of the lobster Ca2+ channel by millimolar Ca2+, whereas 45Ca2+ efflux from mammalian skeletal and cardiac muscle sarcoplasmic reticulum (SR) vesicles is optimally activated by micromolar Ca2+. Further, mammalian muscle SR Ca2+ release activity is modulated by Mg2+ and ATP, whereas neither ligand appreciably affected 45Ca2+ efflux from lobster SR vesicles. These results suggested that lobster and mammalian muscle express immunologically and functionally distinct SR Ca2+ release channel protein complexes.


Oxidation of methyl linoleate in micellar solutions induced by the combination of iron(II)/ascorbic acid and iron(II)/H2O2.
The oxidation of methyl linoleate (ML) was studied in the presence of Fe(II) alone and its combination with either ascorbic acid (AsAH(2)) or hydrogen peroxide (H(2)O(2)) at different molar ratios. Reactions were carried out in micellar solutions of TTAB (tetradecyltrimethylammonium bromide) and SDS (sodium dodecyl sulfate), respectively, and were monitored by UV spectroscopy and electrospray ionization mass spectrometry (ESI-MS). Fe(II) alone was able to catalyze the oxidation of ML in micellar solutions of TTAB, but not in those of SDS. The combination of H(2)O(2) with Fe(II) showed catalytic effect only in the TTAB medium, leading to different ML and Fe(II) oxidation kinetics compared to the Fe(II)-only catalyzed reactions. The AsAH(2)/Fe(II) combination demonstrated to be a good catalyst for the oxidation of ML in SDS micellar solutions, but not in TTAB micellar solutions; the activity of the catalyst was dependent on the AsAH(2)/Fe(II) molar ratio. The obtained results confirm that, for the ML oxidation to be initiated, the presence of a Fe(II)/Fe(III) couple is essential, which is related to the pH of micellar solutions. The catalytic properties of the AsAH(2)/Fe(II) combination were explained by taking into account the anti-oxidant and pro-oxidant properties of AsAH(2), as well as the possible formation of an iron/ascorbate complex as the initiator of the ML oxidation.


Tracking patients with chronic occipital headache after occipital nerve decompression surgery: A case series.
The therapeutic benefit of nerve decompression surgeries for chronic headache/migraine are controversial. To provide clinical characteristics of headache type and treatment outcome of occipital nerve decompression surgery. A retrospective review of clinical records. Inclusion criteria were evidence of chronic occipital headache with and without migrainous features and tenderness of neck muscles, occipital allodynia, and inadequate response to prophylactic drugs. Surgical decompression of the greater and lesser occipital nerves provided complete and extended (3-6 years) relief of new daily persistent headache in case 3 (46 year old female), and of chronic post-traumatic headache in cases 4 and 6 (35 and 30 year old females, respectively), partial relief of chronic headache/migraine in cases 1 and 2 (41 year old female and 36 year old male), and no relief of episodic (cases 3 and 4) or chronic migraine (case 5, 52 year old male), or chronic tension-type headache (case 7, 31 year old male). As a case series, this study cannot test a hypothesis or determine cause and effect. However, the complete elimination of new daily persistent headache and post-traumatic headache, and the partial elimination of chronic headache/migraine in two patients - all refractory to other treatment approaches - supports and justifies the effort to continue to generate data that can help determine whether decompression nerve surgeries are beneficial in the treatment of certain types of chronic headache.


Prevalence and demographic correlates of childhood maltreatment in an adult community sample.
This study had two aims: (1) to determine the prevalence of five categories of retrospectively reported childhood maltreatment in an adult community sample and (2) to examine relationships between three theoretically and practically chosen demographic variables and childhood maltreatment. Participants were a representative sample of 967 adult men and women in the metropolitan Memphis, Tennessee area. They completed a telephone survey that included a reliable, valid questionnaire assessing five types of childhood maltreatment (i.e., emotional abuse, emotional neglect, physical abuse, physical neglect, and sexual abuse) and demographic questions. Simultaneous logistic regression analyses were used to identify demographic correlates of specific trauma types. Prevalence of childhood maltreatment ranged from approximately 30% for women to over 40% for men. Approximately 13% of participants reported multiple forms of maltreatment. The most common forms of trauma for both men and women were physical abuse, physical neglect, and emotional abuse, all of which were highly likely to co-occur. Race, sex, and current educational level were each associated with an increased likelihood of childhood maltreatment; differential relationships with particular maltreatment types were also observed. These findings highlight the importance of research on the prevalence of and risks for multiple types of childhood maltreatment, particularly in the somewhat neglected area of emotional abuse and neglect. These findings can be used to highlight the need for preventive interventions aimed at the negative sequelae of childhood maltreatment and to tailor preventive interventions to the needs and expectations of those at high risk.


Suppressor of cytokine signaling expression with increasing severity of murine hepatic ischemia-reperfusion injury.
Preservation of function requires tight regulation of the cellular events initiated when hepatic ischemia is followed by reperfusion (IR). One important mechanism modulating the cytokine-directed response to injury is Suppressors of Cytokine Signaling. SOCS1 and SOCS3 ensure appropriate intensity and duration of cytokine signaling through negative feedback on JAK-STAT signaling. The contribution of SOCS1 and SOCS3-mediated regulation to the evolution of hepatic IR injury is unknown. C57Blk6 mice were subjected to mild (20 min) or severe (90 min) hepatic ischemia. Liver was analyzed for cytokine and SOCS1/3 induction as well as JAK-STAT activation at intervals after reperfusion. Tnf, Il-1beta, and Il-6 expression paralleled increasing injury severity. Despite early phosphorylation of both STAT1 and STAT3 after severe injury, only nuclear translocation of activated STAT3, suggesting that the induction of target genes through JAK-STAT after IR is predominantly via STAT3. Socs3 was expressed across the injury spectrum while Socs1 was induced only in the face of severe IR injury. Severe IR in Il-6 deficient mice confirmed that Il-6, acting via STAT3, serves as a primary inducer of both regulatory mechanisms. Under the influence of IL-6-mediated STAT3 signaling, Socs1 serves as a complimentary regulatory mechanism when Socs3 is insufficient to limit cytokine-mediated inflammation after hepatic IR.


Protein catabolism in cultures of hepatocytes derived from mice of various ages.
The degradation of pulse-labeled protein was measured in cultures of hepatocytes derived from mice of 3--4, 15--16, and 28 months of age. The rates of protein degradation were determined in culture media with varying amino acid, insulin, and glucagon concentrations. No differences with age were seen. Also no difference with age was detected in the lysosomal degradation of 125I-labeled asialofetuin.


Turbidimetric analysis of human sperm motility.
A turbidimetric method has been developed for determining rapidly the fraction of sperm in human ejaculates which show the most vigorous motility. The method is based on the fact that sperm cells so endowed will be the first to swim upward into clear medium from a concentrated cell suspension at the bottom of an optical cuvette. This results in a time-dependent increase in turbidity in the medium which is recorded spectrophotometrically as an increase in absorbance. The determination requires 10 minutes and yields both the fraction of rapidly moving sperm, FRM, and their average velocity, VRM. Examination of 25 samples yielded FRM values of 10% or lower, whereas values for VRM averaged about 100 microns/second. These vigorously motile cells may be the best candidates for fertilization, and samples with a high fraction of such cells should have high fertilizing capacity. It is suggested that this simple turbidimetric test be used in evaluation of human semen as a possible indicator of fertilizing capacity.


Arachidonate metabolism in bovine gallbladder muscle.
Incubation of (1-14C]arachidonic acid (AA) with homogenates of bovine gallbladder muscle generated a large amount of radioactive material having the chromatographic mobility of 6-keto-PGF1 alpha (stable product of PGI2) and smaller amounts of products that comigrated with PGF2 alpha PGE2. Formation of these products was inhibited by the cyclooxygenase inhibitor indomethacin. The major radioactive product identified by thin-layer chromatographic mobility and by gas chromatography - mass spectrometric analysis was found to be 6-keto-PGF1 alpha. The quantitative metabolic pattern of [1-14C]PGH2 was virtually identical to that of [1-14C]AA. Incubation of arachidonic acid with slices of bovine gallbladder muscle released labile anti-aggregatory material in the medium, which was inhibited by aspirin or 15-hydroperoxy-AA. These results indicate that bovine gallbladder muscle has a considerable enzymatic capacity to produce PGI2 from arachidonic acid.


Patterns in the Pandemic: Disproportionate Patient Burdens Among Regional Hospitals.
To examine the distribution of hospitalized COVID-19 patients among adult acute care facilities in the Greater Philadelphia area and identify factors associated with hospitals carrying higher burdens of COVID-19 patients. In this observational descriptive study, we obtained self-reported daily COVID-19 inpatient censuses from 28 large (>100 beds) adult acute care hospitals in the Greater Philadelphia region during the initial wave of the COVID-19 pandemic (March 23, 2020, to July 28, 2020). We examined hospitals based on their size, location, trauma certification, median household income, and reliance on public insurance. COVID-19 inpatient burdens (ie, beds occupied by COVID-19 patients), relative to overall facility capacity (ie, total beds), were reported and assessed using thresholds established by the Institute of Health Metrics and Evaluation to approximate the stress induced by different COVID-19 levels. Maximum (ie, peak) daily COVID-19 occupancy averaged 27.5% (SD 11.2%) across the 28 hospitals. However, there was dramatic variation between hospitals, with maximum daily COVID-19 occupancy ranging from 5.7% to 50.0%. Smaller hospitals remained above 20% COVID-19 capacity for longer (small hospital median 27.5 days [interquartile range {IQR}: 4 to 32]; medium hospital median 18.5 days [IQR: 0.5 to 37]; large hospital median 13 days [IQR: 6 to 32]). Trauma centers reached 20% capacity sooner (median 19 days [IQR: 16-25] versus nontrauma median 30 days [IQR: 20 to 128]), remained above 20% capacity for longer (median 31 days [IQR: 11 to 38]; nontrauma median 8 days [IQR: 0 to 30]), and had higher observed burdens relative to their total capacity (median 5.8% [IQR: 2.4% to 8.3%]; nontrauma median 2.5% [IQR: 1.6% to 2.8%]). Urban location was also predictive of higher COVID-19 patient burden (urban median 3.8% [IQR: 2.6% to 6.7%]; suburban median 2.2% [IQR: 1.5% to 2.8%]). Heat map analyses demonstrated that hospitals in lower-income areas and hospitals in areas of higher reliance on public insurance also exhibited substantially higher COVID-19 occupancy and longer periods of higher COVID-19 occupancy. Substantial discrepancies in COVID-19 inpatient burdens existed among Philadelphia-region adult acute care facilities during the initial COVID-19 surge. Trauma center status, urban location, low household income, and high reliance on public insurance were associated with both higher COVID-19 burdens and longer periods of high occupancy. Improved data collection and centralized sharing of pandemic-specific data between health care facilities may improve resource balancing and patient care during current and future response efforts.


Synthesis of D-lyxitol and D-ribitol analogues of the naturally occurring glycosidase inhibitor salacinol.
The synthesis of analogues of the naturally occurring glycosidase inhibitor, salacinol, in which the D-arabinitol ring has been replaced by D-lyxitol or D-ribitol, is described. Salacinol is one of the active principles in the aqueous extracts of Salacia reticulata, which are traditionally used in India and Sri Lanka for the treatment of Type II diabetes. The synthetic strategy relies on the nucleophilic attack of 1,4-anhydro-2,3,5-tri-O-p-methoxybenzyl-4-thio-D-lyxitol or 1,4-anhydro-2,3,5-tri-O-p-methoxybenzyl-4-thio-D-ribitol at the least hindered carbon of the benzylidene-protected L-cyclic sulfate derived from L-erythritol. Screening of these compounds against recombinant human maltase glucoamylase (MGA), a critical intestinal glucosidase involved in the processing of oligosaccharides of glucose into glucose itself, shows that they are not effective inhibitors of MGA and demonstrates the importance of the d-arabinitol configuration in the heterocyclic ring for effective inhibition.


The Emotional Facet of Subjective and Neural Indices of Similarity.
Emotional similarity refers to the tendency to group stimuli together because they evoke the same feelings in us. The majority of research on similarity perception that has been conducted to date has focused on non-emotional stimuli. Different models have been proposed to explain how we represent semantic concepts, and judge the similarity among them. They are supported from behavioural and neural evidence, often combined by using Multivariate Pattern Analyses. By contrast, less is known about the cognitive and neural mechanisms underlying the judgement of similarity between real-life emotional experiences. This review summarizes the major findings, debates and limitations in the semantic similarity literature. They will serve as background to the emotional facet of similarity that will be the focus of this review. A multi-modal and overarching approach, which relates different levels of neuroscientific explanation (i.e., computational, algorithmic and implementation), would be the key to further unveil what makes emotional experiences similar to each other.


Growth differentiation factor 15 is an early predictor for persistent organ failure and mortality in acute pancreatitis.
Early prediction of persistent organ failure (POF) is crucial for patients with acute pancreatitis (AP). Growth differentiation factor 15 (GDF15), also known as macrophage inhibitory cytokine 1 (MIC-1), is associated with inflammatory responses. We investigated changes in plasma GDF15 and assessed its predictive value in AP. The study included 290 consecutive patients with AP admitted within 36 h after symptoms onset. Clinical data obtained during hospitalization were collected. Plasma GDF15 levels were determined using enzyme-linked immunosorbent assays. The predictive value of GDF15 for POF was analyzed. There were 105 mild, 111 moderately severe, and 74 severe AP patients. Plasma GDF15 peak level were measured on admission, and significantly declined on the 3rd and 7th day. Admission GDF15 predicted POF and mortality with areas under the curve (AUC) of 0.847 (95% confidence interval [CI] 0.798-0.895) and 0.934 (95% CI 0.887-0.980), respectively. Admission GDF15, Bedside Index of Severity in Acute Pancreatitis, and hematocrit were independent factors for POF by univariate and multivariate logistic regression, and the nomogram built on these variables showed good performance (optimism-corrected c-statistic = 0.921). The combined predictive model increased the POF accuracy with an AUC 0.925 (95% CI 0.894-0.956), a net reclassification improvement of 0.3024 (95% CI: 0.1482-0.4565, P < 0.001), and an integrated discrimination index of 0.11 (95% CI 0.0497-0.1703; P < 0.001). Plasma GDF15 measured within 48 h of symptom onset could help predict POF and mortality in AP patients.


Thoracic trauma. Newer concepts.
Thoracic trauma induces pulmonary injury by functional as well as by structural damage. Injury at the cellular level causes changes seen 24 to 48 hours after initial trauma. Treatment should be aimed at stabilizing the patient upon initial presentation, and one should be aware of potential problems that may arise as the injury progresses. An animal with tracheobronchial tree injury is usually presented a few days after the initial injury with a client complaint of dyspnea. The only treatment is surgical repair.


Antimycotic Studies of Miconazole Nanovesicles Formulation vs Candida Strain.
Present research work was aimed at formulation and evaluation of antifungal activity of miconazole nitrate (MN) vesicles vs C. albicans spp.
 Miconazole loaded vesicles were prepared by coacervation phase separation technique using nonionic surfactants and stabilizers. The antimycological activity of vesicles was performed using agar disc diffusion technique.
 The miconazole nitrate lipid vesicles F5A and F5B showed maximum activity with higher zones of inhibition ie, 13.95+1.54 mm and 13.64+0.65 mm, respectively, after 3 days (For all comparisons, P<.05 was considered significant).
 The findings of this study suggest antifungal potential of a novel preparation of miconazole nitrate vesicles vs Candida albicans in the treatment of mycoses in dermatological practice.

 J Drugs Dermatol. 2016;15(6):734-737.


The basic helix-loop-helix transcription factor, Mist1, induces maturation of mouse fetal hepatoblasts.
Hepatic stem/progenitor cells, hepatoblasts, have a high proliferative ability and can differentiate into mature hepatocytes and cholangiocytes. Therefore, these cells are considered to be useful for regenerative medicine and drug screening for liver diseases. However, it is problem that in vitro maturation of hepatoblasts is insufficient in the present culture system. In this study, a novel regulator to induce hepatic differentiation was identified and the molecular function of this factor was examined in embryonic day 13 hepatoblast culture with maturation factor, oncostatin M and extracellular matrices. Overexpression of the basic helix-loop-helix type transcription factor, Mist1, induced expression of mature hepatocytic markers such as carbamoyl-phosphate synthetase1 and several cytochrome P450 (CYP) genes in this culture system. In contrast, Mist1 suppressed expression of cholangiocytic markers such as Sox9, Sox17, Ck19, and Grhl2. CYP3A metabolic activity was significantly induced by Mist1 in this hepatoblast culture. In addition, Mist1 induced liver-enriched transcription factors, CCAAT/enhancer-binding protein α and Hepatocyte nuclear factor 1α, which are known to be involved in liver functions. These results suggest that Mist1 partially induces mature hepatocytic expression and function accompanied by the down-regulation of cholangiocytic markers.


Laser-induced pain for evaluation of local analgesia: a comparison of topical application (EMLA) and local injection (lidocaine).
High-energy lasers are suitable for experimental pain stimulation because they selectively activate the polymodal nociceptors. Argon laser light penetrates deep into the skin and makes this laser type preferable for simulating pain arising from surgical skin incisions. Short argon laser pulses were applied to the skin and three parameters were quantified before and during analgesia; sensory threshold, pain threshold, and the pain-related cortical response (latency and amplitude). Determination of sensory and pain thresholds made it possible to distinguish between two levels of analgesia; the pain block, where no pain was felt but other sensations were still perceived; and total sensory block, where the laser stimulus elicited no sensations of any type. The analgetic effects of cutaneous injections of lidocaine and topical application of EMLA (eutectic mixture of local anesthetics) cream were evaluated and compared by means of the introduced parameters. Lidocaine produced total sensory block almost immediately after injection, which was associated with the absence of cortical response to cutaneous laser stimulation. When the EMLA cream was applied for 15 minutes, both sensory and pain thresholds increased. During the next 30 minutes after removal of the cream, the thresholds increased further. The increase in analgetic effect after removal of the cream was studied using different times (15, 30, 60, 80, 100, and 120 minutes) for topical EMLA cream application. Total sensory block was reached 20 minutes after removal of application for 80 minutes or immediately after removal of the cream after it was applied for 100 or 120 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)


Characterization of Reca Mediated homologous pairing on nitrocellulose membrane.
Reactions between a single-stranded DNA (ssDNA) and a double-stranded DNA (dsDNA) provide an efficient model to study RecA promoted homologous recombination. We have devised an assay in which the ssDNA is first bound to a nitrocellulose membrane. RecA protein is loaded on this membrane (loading step) which is then incubated with a labelled homologous dsDNA (incubation step). Since this assay can be used for study of mutant RecA proteins or RecA-like activities in crude extracts from other organisms, we have characterized the reaction promoted on the membrane. Under these new conditions, the reaction keeps the main characteristics observed with classical assays performed in solution: increasing NaCl concentration destabilized the RecA-DNA complex, ATP gamma S was required for formation of stable RecA-DNA complex, initiation of the reaction exhibits the same polarity as in classical assays, a complete strand exchange with a 44 bp long duplex oligonucleotide has been recorded under our conditions. Moreover, our results indicate that the binding of RecA protein itself to the nitrocellulose membrane did not impair its ability to promote homologous pairing. Pairing reactions involving long dsDNA (6407 bp) were more efficient with hydrolysable ATP than with ATP gamma S only when the ssDNA was bound to the membrane. Furthermore, ATP hydrolysis was not required when using short dsDNA (44 bp). These results constitute experimental support for a new role for the ATPase activity of RecA protein: the energy produced could favor the initiation of RecA mediated recombination involving long stretches of DNA which have restricted freedom to rotation.


Identifying distinct trajectories of change in young breast cancer survivors' sexual functioning.
To identify and characterize distinct trajectories of change in young women's sexual functioning over the first 5 years following breast cancer diagnosis. Group-based trajectory modeling was applied to the sexual functioning of 896 women diagnosed with stage I-IV breast cancer at age 40 or younger. The Cancer Rehabilitation Evaluation System was used to evaluate women's symptoms of sexual dysfunction annually for 5 years. Five distinct trajectories of sexual functioning were identified: one asymptomatic, one minimally symptomatic, two moderately symptomatic, and one severely symptomatic trajectory. Twelve percent of women were asymptomatic throughout follow-up. The plurality of women experienced stable mild symptoms (42%). Among those with moderate symptoms, some experienced improvement over time (22%) while others experienced deterioration (13%); 11% experienced stable severe symptoms that did not remit over time. Independent predictors of experiencing a symptomatic rather than asymptomatic trajectory (P < 0.05, two-sided) included diagnosis with stage 2 versus 1 disease, ER positive disease treated with oophorectomy or ovarian suppression, being partnered, having anxiety, poorer body image, and greater musculoskeletal pain. We identified distinct trajectories that describe the reported sexual symptoms in this cohort of young breast cancer survivors. The majority of women reported various degrees of sexual dysfunction that remained stable over the study period. There is, however, potential for improvement of moderate and severe symptoms of sexual dysfunction in early survivorship.


Synchronization of fractional-order complex-valued neural networks with time delay.
This paper deals with the problem of synchronization of fractional-order complex-valued neural networks with time delays. By means of linear delay feedback control and a fractional-order inequality, sufficient conditions are obtained to guarantee the synchronization of the drive-response systems. Numerical simulations are provided to show the effectiveness of the obtained results.


CD4+ T cells migrate from airway to bone marrow after antigen inhalation in rats.
IL-5-producing T lymphocytes increase in rat bone marrow after inhalational challenge with allergen. To test the hypothesis that T cells migrate from the airways to the marrow, we examined the trafficking of T cells in Brown Norway rats after sensitization and challenge with ovalbumin. Purified CD4+ T cells, harvested from cervical lymph nodes of naive and ovalbumin-sensitized donors, were labeled with carboxy fluorescein diacetate succinimidyl ester; 20 x 10(6) cells were placed in the trachea of naive or sensitized recipients under anesthesia, and 18 hours later, animals were challenged with inhaled ovalbumin. Cells were harvested 24 hours later from the bone marrow, bronchoalveolar lavage fluid, lungs, the lung blood pool of cells, lung draining lymph nodes, peripheral blood, and spleen. The number of carboxy fluorescein diacetate succinimidyl ester-positive cells, measured by fluorescence-activated cell sorter, in the bone marrow of ovalbumin sensitized, primed T-cell recipients was higher than either the sham-sensitized, primed T-cell recipients or sham-sensitized, naive T-cell recipients (P < .05). The number of eosinophils in both bone marrow and bronchoalveolar lavage fluid was increased in ovalbumin-sensitized, primed T-cell recipients. The expression of the T-cell chemoattractants eotaxin and IL-16, evaluated by immunohistochemistry, was higher in the bone marrow of ovalbumin-sensitized, primed T-cell recipients. CD4+ T cells travel from airway to bone marrow after antigen inhalation. The homing of the CD4+ T cells might be facilitated by eotaxin and IL-16 expression in the bone marrow and might contribute to the stimulation of eosinophilopoiesis after airway allergen exposure.


Malignant pericardial effusion in endometrial adenocarcinoma.
A case of endometrial adenocarcinoma in a 62-year-old woman with malignant pericardial effusion is presented. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic node dissection, and paraaortic node biopsy. Postoperatively, she was placed on a combination chemotherapy regimen of cisplatin, doxorubicin, and cyclophosphamide. The patient developed cardiac tamponade during the course of chemotherapy. Although we first suspected cardiotoxic effect of doxorubicin, cytologic examination revealed adenocarcinoma cells in the pericardial fluid. A review of the literature revealed no other cases of cardiac metastasis from endometrial carcinoma diagnosed during life.


Acute aortic dissection after off-pump coronary artery surgery.
Iatrogenic aortic dissection has been described, albeit infrequently, after coronary artery surgery performed under cardiopulmonary bypass. Since the advent of beating heart coronary surgery, several authors have described an apparent increase of this complication related to the application of a lateral clamp on the ascending aorta to perform the proximal anastomosis. We describe the case of a 70 years old patient who presented aortic dissection, with immediate paraplegia, 7 days after off-pump coronary surgery.


An integrative review of the evidence for Shinrin-Yoku (Forest Bathing) in the management of depression and its potential clinical application in evidence-based osteopathy.
There is growing interest in the idea of integrating Nature Therapies into the multidisciplinary management of complex conditions such as depression. Shinrin-Yoku (Forest Bathing), a practice involving spending time in a forested environment while paying attention to multi-sensory stimuli has been proposed as one such modality. The objectives of this review were to critically analyse the current evidence base on the efficacy of Shinrin-Yoku for the treatment of depression, and to examine how the findings may reflect and/or inform osteopathic principles and clinical practice. An integrative review of the evidence for Shinrin-Yoku in the management of depression published between 2009 and 2019 was conducted resulting in n = 13 peer-reviewed studies meeting inclusion criteria. Two themes emerged from the literature, the positive effect of Shinrin-Yoku on self-reported mood scores, and physiological changes arising from forest exposure. However, the methodological quality of the evidence is poor and experiments may not be generalisable. Suggestions were made for improving the research base via mixed-method studies in a biopsychosocial framework, and aspects of the research which may be applicable to evidence-based osteopathy were noted.


Parallel clinical and behavioural studies of adjuvant-induced arthritis in the rat: possible relationship with 'chronic pain'.
The course of adjuvant-induced arthritis was followed, over an 11-week postinoculation period, in Sprague-Dawley rats, using both clinical and behavioural methods of study. Clinical observations included body weight, diameters of radiocarpal and tibiotarsal joints and radiological analysis of forepaws, hindpaws and vertebrae. Behavioural observations included those of spontaneous behaviour-mobility, exploring, rearing, penis licking and scratching-and of pain-related tests-the foot-bend procedure and Randall-Selitto test. In general, the time course of the disease could be divided into 4 stages, viz. a preclinical, an acute, a postacute and a recovery stage. The preclinical stage (first week) was characterized by discrete radiological lesions of the forepaws and a slight increase in the threshold for struggle triggered by foot pressure, but, above all, by no change in the other parameters. The acute stage (weeks 2-4) was clearly defined by a pause in body weight gain and by dramatic behavioural changes: a lack of mobility and exploring behaviour, a profound increase in scratching behaviour and signs of hyperalgesia. During this period, hindpaw and forepaw joint diameters increased dramatically. The behavioural modifications peaked at the same time (week 4) as there was an acceleration in the radiological abnormalities (soft tissue swelling, demineralization and erosion of bone extremities and joint space narrowing) which had begun during week 3. During the postacute stage (weeks 5-8), body weight and behavioural reactions began to return towards control values, but joint diameters and radiological scores either continued to increase or remained constant. During the recovery stage (weeks 9-11), behavioural scores and body weight returned to control values while the mean joint diameters remained constant and there was a slight decrease in the radiological scores. In spite of the complexity of the model used in these studies, it appeared quite clear that the acute phase of the disease was characterized by the onset of clinical symptoms and dramatic changes in behaviour, all of which could be related to the occurrence of pain; signs of pain were still present, albeit weaker, in the postacute phase. Such observations, taken together, help to validate adjuvant arthritis as an experimental model of chronic pain in Sprague-Dawley rats.


Which nutritional measurements assess protein-energy nutritional status in patients receiving home parenteral nutrition?
Weight, midarm circumference, triceps skinfold thickness, arm muscle circumference, albumin, prealbumin, transferrin and total lymphocyte count were measured at each outpatient visit in patients reveiving home parenteral nutrition from September 1987 to November 1991. Each nutritional variable was analysed for individuals and for the whole group. Group data were expressed using the actual values obtained and successive differences (the change between clinic attendances). Nutritional variables were evaluated using a correlation matrix. Identical analysis of individual and group data demonstrates that laboratory investigations are of little value in the assessment of nutritional status in patients receiving home parenteral nutrition. Anthropometry detected changes in body weight secondary to changes in muscle and/or fat in 80% of patients. Pooling anthropometric data distors the relationship between variables owing to inter-individual variability when actual values are used. The method of successive differences is the preferred method of analysis for group anthropometric data.


Quinine potently blocks single K+ channels activated by dopamine D-2 receptors in rat corpus striatum neurons.
In single channel recordings from acutely dissociated neurons of the rat corpus striatum, a membrane K+ channel which is activated by dopamine D-2 receptors was blocked by nanomolar concentrations of quinine. An intermittent partial blockade was observed at 4-10 nM quinine, with a voltage dependence consistent with quinine binding to the channel near the extracellular surface of the membrane. A nearly complete blockade of channel current was observed at 100 nM quinine and above. Such concentrations are known to be too low to block various other ion channels, and may be attained in human brain at antimalarial dosages of quinine. Blockade of this channel by quinine may provide a useful experimental probe of dopaminergic function, as an alternative to D-2 receptor binding site blockade by neuroleptics.


Targeted gene transfer to hepatocellular carcinoma cells in vitro using a novel monoclonal antibody-based gene delivery system.
Gene therapy approaches for the treatment of malignant tumors will require high-level expression of therapeutic genes in tumors compared with normal tissues. This may be achieved either by targeted gene delivery to tumor cells or by the use of tumor-specific promoters. Here, we describe the use of a novel conjugate consisting of a tumor-reactive monoclonal antibody (mAb), designated AF-20, coupled to a DNA-binding cationic amphiphile, cholesteryl-spermine, for gene delivery to hepatocellular carcinoma (HCC) cells. The high-affinity mAb, AF-20, recognizes a rapidly internalized 180-kd cell-surface glycoprotein that is abundantly expressed on HCC and other human tumors. The AF-20 mAb and an isotype-matched control antibody (C7-57) were covalently coupled to cholesteryl-spermine. Binding and internalization of AF-20-cholesteryl-spermine was confirmed by fluorescence microscopy using fluorescein isothiocyanate (FITC)-labeled anti-mouse IgG antibody. Following transfection of FITC-labeled oligonucleotides and ethidium monoazide-labeled plasmid DNA, cellular uptake and intracellular localization of nucleic acids were examined by laser scanning confocal microscopy. Transfection of luciferase or beta-galactosidase reporter genes complexed to AF-20-cholesteryl-spermine resulted in high levels of gene expression in AF-20 antigen-positive tumor cells. Very low levels of gene expression were observed using the control compound (C7-57-cholesteryl-spermine), which does not recognize the AF-20 tumor antigen or when AF-20 antigen-negative NIH 3T3 cells were transfected with AF-20-cholesteryl-spermine. Thus, covalent coupling of the AF-20 mAb to cholesteryl-spermine generated a highly specific and efficient nonviral vector system for targeted gene delivery to AF-20 antigen-positive HCC cells.


Immunodiagnosis of fasciolosis in ruminants using a 28-kDa cysteine protease of Fasciola gigantica adult worms.
A homogeneous extract of a 28-kDa cysteine protease of Fasciola gigantica adult worms was used as the antigen for immunodiagnosis of fasciolosis in cattle, sheep and goats using the Falcon assay screening test enzyme-linked immunosorbent assay technique. This antiprotease assay technique was found to be very rapid and sensitive and may be useful as a supplementary method for the diagnosis of fasciolosis in ruminants.


Red fluorescent materials based on julolidine/chromene with the bulky tert-butyl and trimethylsilyl substituents for organic light-emitting diodes.
In this work, we designed and synthesized two red emitters 2-(6,8-di-tert-butyl-2-(2-(1,1-dimethyl-7-(trimethylsilyl)-7-((trimethylsilyl)methyl)-1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinolin-9-yl)vinyl)-4H-chromen-4-ylidene)malononitrile (Red 1) and 2-(6,8-di-tert-butyl-2-(2-(1,1,7-trimethyl-7-t-butyl)-1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinolin-9-yl)vinyl)-4H-chromen-4-ylidene)malononitrile (Red 2). To explore the electro-luminescence properties of these materials, multilayered OLEDs using these materials as dopants in a Alq3 host were fabricated. Particularly, by using Red 1 as a dopant in emitting layer, device 1 showed the luminous and power efficiencies of 0.81 cd/A and 0.43 lm/W at 20 mA/cm2, respectively. The CIE coordinates of this device was (0.65, 0.34) at 7.0 V, which is close to the NTSC standard CIE coordinates of (0.67,0.32) for red emission.


Oral malodorous compound causes apoptosis and genomic DNA damage in human gingival fibroblasts.
Volatile sulfur compounds are the main cause of halitosis. Hydrogen sulfide is one of these volatile sulfur compounds and the principal malodorous compound in physiological halitosis. Periodontally pathogenic activities of hydrogen sulfide have been previously reported. Hydrogen sulfide induces apoptotic cell death in aorta smooth muscle cells and in other tissues. Apoptosis plays an important role in the onset and progress of periodontitis. The objective of this study was to determine whether hydrogen sulfide causes apoptosis in human gingival fibroblasts. Necrotic cells were detected using a lactate dehydrogenase assay. Apoptosis was ascertained using a histone-complexed DNA fragment assay and flow cytometry. The level of caspase 3, a key enzyme in apoptotic signaling, was also measured, and the effects of hydrogen sulfide on reactive oxygen species and superoxide dismutase were assessed. DNA damage caused by hydrogen sulfide was examined by means of single-cell gel electrophoresis. After 72 h of incubation with 100 ng/mL of hydrogen sulfide, necrosis was found in less than 10% of human gingival fibroblasts, whereas apoptosis was significantly increased (p < 0.05). Superoxide dismutase activity was strongly inhibited, and reactive oxygen species production was enhanced, after 48 and 72 h of incubation. Caspase 3 activity was also increased after 72 h of incubation (p < 0.01). Tail length, percentage of DNA in tail, and tail moment, measured by single-cell gel electrophoresis, were also intensified after 72 h of incubation (p < 0.001). Hydrogen sulfide caused apoptosis and DNA damage in human gingival fibroblasts. An increased level of reactive oxygen species stimulated by hydrogen sulfide may induce apoptosis and DNA strand breaks.


Cyclized proteins with tags as permeable and stable cargos for delivery into cells and liposomes.
Despite the therapeutic potential of recombinant proteins, their cell permeabilities and stabilities remain significant challenges. Here we demonstrate that cyclized recombinant proteins can be used as universal cargos for permeable and stable delivery into cells and polydiacetylene liposomes. Utilizing a split intein-mediated process, cyclized model fluorescent proteins containing short tetraarginine (R4) and hexahistidine (H6) tags were generated without compromising their native protein functions. Strikingly, as compared to linear R4/H6-tagged proteins, the cyclized counterparts have substantially increased permeabilities in both cancer cells and synthetic liposomes, as well as higher resistances to enzymatic degradation in cancer cells. These properties are likely a consequence of structural constraints imposed on the proteins in the presence of short functional peptides. Additionally, photodynamic therapy by cyclized photoprotein-loaded liposomes in cancer cells was significantly improved in comparison to that by their non-cyclized counterparts. These findings suggest that our strategy will be universally applicable to intercellular delivery of proteins and therapeutics.


Cardiac toxicity and efficacy of trastuzumab combined with pertuzumab in patients with [corrected] human epidermal growth factor receptor 2-positive metastatic breast cancer.
To evaluate safety and efficacy of trastuzumab with pertuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who had progressive disease on trastuzumab-based therapy. Patients with measurable HER2(+) metastatic breast cancer, < or = 3 trastuzumab-based regimens, and left ventricular ejection fraction (LVEF) > or = 55% received 8 or 6 mg/kg trastuzumab and 840 mg pertuzumab i.v. followed by 6 mg/kg trastuzumab and 420 mg pertuzumab every 3 weeks. Cardiac evaluation and tumor response were assessed every 3 and 6 weeks, respectively. Eleven patients received 64 cycles of trastuzumab plus pertuzumab. A total of 92 echocardiograms and 8 cardiac magnetic resonance imaging studies were done. With the lower limit of normal LVEF 55%, left ventricular systolic dysfunction was observed in six patients, three grade 1, two grade 2, and one grade 3 according to the National Cancer Institute Common Terminology Criteria for Adverse Events. The objective response rate was 18%. Two patients had partial responses, three had stable disease, and six had progressive disease. The median time to progression was 6 weeks. In baseline tumors from formalin-fixed paraffin-embedded primary and/or metastatic tumor biopsies, pHER2-Y1248 trended toward an increase in patients with partial response compared with those with stable disease/progressive disease (P = 0.095). Trastuzumab plus pertuzumab may have clinical benefit in selected patients who have previously been treated with trastuzumab. Cardiac toxicity, although asymptomatic in most cases, was associated with this treatment. Further evaluation of efficacy of this combination is required to define the overall risks and benefits.


Microcomputer-based interactive tracking of blood cells at biomaterial surfaces.
A microcomputer-based system for analyzing the motion of human platelets and leukocytes at synthetic surfaces from a sequence of video frames on tape is described. The software is designed to provide convenient interaction with an operator to reduce the burden of manual analysis. In addition, the system computes and stores the cell movement data on disk for subsequent statistical analysis. Measurement include the number and nature of cell-to-surface collisions, residence times, and distances traveled.


Antitumor and antimetastatic actions of eicosapentaenoic acid ethylester and its by-products formed during accelerated stability testing.
The aim of the present work was to compare the effects of eicosapentaenoic acid (EPA) ethylester and EPA derivatives (EPAD) on tumor growth and metastasis to the lung in tumor-bearing mice. Because EPA is very unstable during long-term storage, the EPAD were subjected to accelerated testing under storage conditions of 60 +/- 5% relative humidity at 37 degrees C for 30 days. EPAD are composed of a mixture of a newly identified EPA ethylester dimer and EPA hydroxyethylester, and known EPA and EPA ethylesters. The inhibitory effects of EPAD, the EPA ethylester dimer and EPA hydroxyethylester on Matrigel-induced capillary-like network formation were stronger than the effect of EPA ethylester. The oral administration of EPAD (300 or 1000 mg/kg) inhibited angiogenesis in gels containing Matrigel supplemented with vascular endothelial growth factor (VEGF) and heparin in an in vivo model, but EPA ethylester had no effect. EPA ethylester (300 or 1000 mg/kg) or EPAD (1000 mg/kg) inhibited tumor growth in mice with subcutaneously implanted LLC. Furthermore, EPAD inhibited metastasis to the lung in mice implanted with LLC subcutaneously, but EPA had no effect. EPAD increased the CD8(+) T-cell population in the spleen compared with mice with subcutaneously implanted LLC. EPA ethylester increased the natural killer cell population in the spleen. Thus, it is suggested that the mechanisms of the antitumor and/or antimetastatic actions of EPAD and EPA ethylester involve different immune functions, and that the EPA ethylester dimer and the EPA hydroxyethylester of EPAD may contribute to these actions.


Potential related to no-go reaction of go/no-go hand movement task with color discrimination in human.
Twenty-three human subjects were asked to perform a go/no-go reaction-time hand movement task with discrimination between different color light signals, and potentials related to the discrimination task were recorded with plate electrodes placed on the scalp and analyzed by averaging procedures. A negative potential was found to be recorded specifically to no-go trials in the frontal-parietal part of 21 subjects out of 23 tested. In referring to our recent experiments with monkeys, it is suggested that the potential is related to the judgement not to move and/or the suppression of motor execution.


Integrating health services for HIV infection, diabetes and hypertension in sub-Saharan Africa: a cohort study.
HIV, diabetes and hypertension have a high disease burden in sub-Saharan Africa. Healthcare is organised in separate clinics, which may be inefficient. In a cohort study, we evaluated integrated management of these conditions from a single chronic care clinic. To determined the feasibility and acceptability of integrated management of chronic conditions in terms of retention in care and clinical indicators. Prospective cohort study comprising patients attending 10 health facilities offering primary care in Dar es Salaam and Kampala. Clinics within health facilities were set up to provide integrated care. Patients with either HIV, diabetes or hypertension had the same waiting areas, the same pharmacy, were seen by the same clinical staff, had similar provision of adherence counselling and tracking if they failed to attend appointments. Retention in care, plasma viral load. Between 5 August 2018 and 21 May 2019, 2640 patients were screened of whom 2273 (86%) were enrolled into integrated care (832 with HIV infection, 313 with diabetes, 546 with hypertension and 582 with multiple conditions). They were followed up to 30 January 2020. Overall, 1615 (71.1%)/2273 were female and 1689 (74.5%)/2266 had been in care for 6 months or more. The proportions of people retained in care were 686/832 (82.5%, 95% CI: 79.9% to 85.1%) among those with HIV infection, 266/313 (85.0%, 95% CI: 81.1% to 89.0%) among those with diabetes, 430/546 (78.8%, 95% CI: 75.4% to 82.3%) among those with hypertension and 529/582 (90.9%, 95% CI: 88.6 to 93.3) among those with multimorbidity. Among those with HIV infection, the proportion with plasma viral load <100 copies/mL was 423(88.5%)/478. Integrated management of chronic diseases is a feasible strategy for the control of HIV, diabetes and hypertension in Africa and needs evaluation in a comparative study.


Proteomic analysis of embryonic kidney development: Heterochromatin proteins as epigenetic regulators of nephrogenesis.
Elucidation of the mechanisms underlying the nephrogenesis will boost enormously the regenerative medicine. Here we performed 2-D gel-based comparative proteome analyses of rat embryonic kidney from different developmental stages. Out of 288 non-redundant identified proteins, 102 were common in all developmental stages. 86% of the proteins found in E14 and E16 were identical, in contrast only 37% of the identified proteins overlap between E14 and P1. Bioinformatics analysis suggests developmental stage-specific pathway activation and highlighted heterochromatin protein 1 (Cbx1, Cbx3, Cbx5) and Trim28 as potential key players in nephrogenesis. These are involved in the epigenetic regulation of gene silencing and were down-regulated in the course of kidney development. Trim28 is a potential epigenetic regulator of the branching inhibitor Bmp4. Silencing of Trim28 in cultured kidneys resulted in branching arrest. In contrast knockdown of Cbx5 was associated with abnormal ureteric bud growth and slight impairment of branching. ChIP analysis showed that the H3K9me3 distribution on Bmp4 promoters at E14 and E19 inversely correlate with mRNA expression levels. The concentrated expression-pattern of heterochromatin proteins and the negative impact of their silencing on kidney development, suggest an important role in reciprocal and inductive signaling between the ureteric bud and the metanephric mesenchyme.


Re-irradiation of recurrent head and neck carcinomas: comparison of robust intensity modulated proton therapy treatment plans with helical tomotherapy.
To test the hypothesis that the therapeutic ratio of intensity-modulated photon therapy using helical tomotherapy (HT) for retreatment of head and neck carcinomas can be improved by robust intensity-modulated proton therapy (IMPT). Comparative dose planning with robust IMPT was performed for 7 patients retreated with HT. On average, HT yielded dose gradients steeper in a distance ≤ 7.5 mm outside the target (p<0.0001, F-test) and more conformal high dose regions down to the 50% isodose than IMPT. Both methods proved comparably robust against set-up errors of up to 2 mm, and normal tissue exposure was satisfactory. The mean body dose was smaller with IMPT. IMPT was found not to be uniformly superior to HT and the steeper average dose fall-off around the target volume is an argument pro HT under the methodological implementations used. However, looking at single organs at risk, the normal tissue sparing of IMPT can surpass tomotherapy for an individual patient. Therefore, comparative dose planning is recommended, if both methods are available.


[Late onset visual aura associated with a carotid artery stenosis reversible after endarterectomy].
Visual aura is the most common type of aura. Onset of visual aura occurring for the first time in an elderly person is atypical, even though late-life migraine accompaniments are well-recognized. We report the case of a 72-year-old woman with a past history of migraine without aura since adolescence (one attack per month), who experienced for the first time of her life multiple visual aura over a period of more than one year. These auras were always left homonymous hemianopia which developed gradually over 5 mins followed by severe migraine headache without strict lateralization. The patient was known to have a moderate right carotid artery stenosis. In October 2007, she suffered a minor ischemic stroke in the right carotid artery territory due to progression to severe stenosis of the right internal carotid artery. After carotid endarterectomy, she had no further migraine attacks with aura. We discuss the mechanism of aura in our case with probable microemboli due to the severe right internal carotid artery stenosis responsible for repeated cortical spreading depression. Clinicians should bear in mind to systematically explore all patients with late onset aura including patients who have previously suffered from migraine without aura and also to explore patients who have a dramatic increase of aura even if they are already migrainers with aura.


Neurotoxicology and drug-related disorders.
Neuropsychiatric disorders caused by toxic substances pose a great diagnostic challenge due to the large variety of changes caused in the central and peripheral nervous system. The pathogenetic mechanisms at work are multifaceted and partly not solved. In human drug abusers (cannabis, opiates, cocaine, amphetamines, methamphetamine and "designer drugs"), a broad spectrum of central nervous system alterations are observed including infarction, intracerebral and subarachnoidal hemorrhage, hypoxic-ischemic leukoencephalopathy, infections, neuronal loss, specific astroglial and microglial reaction patterns, and vascular changes, including the endothelial cell as well as the basal lamina.


Optimizing the technique of right laparoscopic adrenalectomy with a modified trocar arrangement and dynamic liver retraction: a comparative study with standard technique.
Right Laparoscopic adrenalectomy (LA) is technically more challenging than left LA, because of the anatomical position of the right adrenal gland and vein. We modified the technique for right LA to optimize the procedure, and compared the operative outcome with standard technique. The operative outcome of 13 cases of right adrenal mass treated with modified LA were compared retrospectively with 29 cases of standard right LA. For modified right LA, we used a 4-port transperitoneal laparoscopic approach that omitted the subxiphoid trocar (classically used for liver retraction), and instead, an assistant applied continuous, dynamic upward liver retraction in a plane perpendicular to the inferior vena cava (IVC). Modified Right LA was done in 13 patients (3 men, 23.1%), without difficulty and with excellent direct exposure of the upper and medial aspect of the adrenal gland and adrenal vein. Mean operative time was significantly shorter compared with standard technique (122.3 ± 20.1 vs. 165 ± 33.6 min; P < 0.0001) There were no bleeding complication and open conversion in modified technique which was promising compared with 2 bleeding complications in our experience with 29 cases of right LA using standard technique. Modified right LA with a 4-port approach and dynamic upward liver retraction in a plane perpendicular to IVC resulted in direct exposure of the upper and medial aspect of the adrenal gland and adrenal vein. This approach can be effective in challenging cases when the infrahepatic fossa is poorly exposed.


A comparison of the effects of corticosterone and cortisol on intermediary metabolism of Calotes versicolor.
Corticosterone and cortisol administered to Calotes versicolor significantly increased the concentrations of blood glucose and urea (liver and kidney), the specific activities of glucose-6-phosphatase (liver and kidney), and glutamic oxaloacetic transaminase (liver and heart); they markedly reduced hepatic cholesterol level and did not change the activities of acid phosphatase (liver and kidney) and glutamic pyruvic transaminase (liver), when compared to vehicle-treated controls.


Simultaneous aortic reconstruction and renal revascularization: risk factors and late results in eighty-nine patients.
From 1973 through 1984, graft replacement of infrarenal aortic aneurysms (N = 56) or occlusive disease (N = 33) was performed in conjunction with simultaneous renal revascularization in 89 patients. Isolated renal artery stenosis was corrected by unilateral reconstruction in 56 patients (63%), but the remaining 33 (37%) had diffuse involvement that required either bilateral renal artery grafts or unilateral revascularization of solitary kidneys. The incidence of hypertension (greater than 180/90 mm Hg) refractory to preoperative medical therapy (88%), severe coronary disease documented by angiography (40%), and postoperative azotemia (33%) or oliguric renal failure (15%) was significantly higher among patients with bilateral renal artery disease (p less than 0.05). In addition, this group had twice the early mortality rate (15%) of patients having unilateral renal artery lesions (7.1%). During a mean follow-up interval of 37 months, medical control of hypertension was enhanced in 46 of the 80 operative survivors (58%), and renal function improved or remained stable in 63 survivors (79%). Five-year actuarial survival presently is 65% for the entire series, with a cumulative mortality rate of 38% among patients who underwent aneurysm resection (mean age 64 years) in comparison to 15% (p = 0.03) for those patients with aortoiliac occlusive disease (mean age 60 years).


Lateral Centre of Mass Displacement can predict running in adults with traumatic brain injury.
Running is an important skill that improves a person's ability to participate in community-based social, leisure and work activities, and therefore improve quality of life. Following traumatic brain injury, many ambulant people are unable to run. Whilst established for walking, the physical impairments that limit running following traumatic brain injury remain unknown. Therefore, the primary aim of this study was to identify which physical impairments contribute to a person's ability to run post traumatic brain injury. In this study, 88 adults with traumatic brain injury were included. Runners and non-runners were compared regarding their clinical assessment of physical impairments, including postural control, focal muscle spasticity, muscle strength, self-selected walking speed and ability to run. Participants also completed a three-dimensional quantitative gait analysis to assess motor skill using the Gait Profile Score. Logistic regression was applied to identify the most important predictors for the ability to run. Significant differences between runners and non-runners were found for postural control, motor control and strength. Dynamic postural control, measured by lateral center of mass displacement, was the best predictor of running, with every centimeter increase in lateral center of mass movement during walking associated with a 30% reduction in the chance of being able to run. Lateral center of mass displacement should be considered when selecting interventions for ambulant patients with the goal to run. Although postural control, motor control and muscle strength were all different between runners and non-runners, they did not contribute to a person's ability to run.


Multiclass method for pesticides quantification in honey by means of modified QuEChERS and UHPLC-MS/MS.
Bee products can be produced in an environment contaminated by pesticides that can be transported by honey bees to the hive and incorporated into the honey. Therefore, rapid and modern methods to determine pesticide residues in honey samples are essential to guarantee consumers' health. In this study, a simple multiresidue method for the quantification of 116 pesticides in honey is proposed. It involves the use of a modified QuEChERS procedure followed by UHPLC-MS/MS analysis. The method was validated according to the European Union SANCO/12571/2013 guidelines. Acceptable values were obtained for the following parameters: linearity, limit of detection (0.005mg/kg) and limit of quantification (0.010 and 0.025mg/kg), trueness (for the four tested levels the recovery assays values were between 70 and 120%), intermediate precision (RSD<20.0%) and measurement uncertainty tests (<50.0%). The validated method was applied for determination of 100 honey samples from five states of Brazil.


Utilization of Hydroxyurea Among Patients Diagnosed with Sickle Cell Disease in Jazan, Saudi Arabia.
The early diagnosis of sickle cell disease (SCD) patients and getting appropriate treatment are crucial for improving clinical outcomes. This study aims to assess the use of hydroxyurea among patients diagnosed with SCD and assess factors influencing the attitude toward the medication and the reasons for discontinuation. This study was a cross-sectional investigation targeting parents or caregivers of children diagnosed with SCD in the Jazan region of Saudi Arabia. Data were collected from tertiary healthcare hospitals via a self-administered questionnaire. The questionnaire was composed of sections measuring the participants' demographics, the number of children diagnosed with SCD, the use of hydroxyurea, and the parents' beliefs about hydroxyurea. There were 301 parents or caregivers recruited. The majority of the recruited participants were mothers (54.5%), and nearly half of the sample were older than 35. More than 80% of the participants declare that one or more of their children are receiving hydroxyurea to manage SCD. The majority of participants declared that using hydroxyurea reduced the frequency of body pain episodes, emergency department visits, and hospital admissions. Participants' major concern about the use of hydroxyurea was related to the fear of weakening their immunity (29.5%) and hydroxyurea's perceived effect on fertility (16.8%). Furthermore, 52 (18%) of the participants declared that the use of hydroxyurea to manage the disease was stopped; the main reasons for stopping was their belief that hydroxyurea had side effects and its impact on weakening of their immune system. The findings indicate the importance of increasing the role of clinicians in educating patients and caregivers about the use of hydroxyurea and its benefits.


The Impact of Endoscopic Endonasal Surgery on Quality of Life in Patients with Malignant Tumors of the Anterior Skull Base: A Prospective Study.
To investigate the effects of endoscopic endonasal surgery (EES) on longitudinal quality of life (QoL) in patients with malignant tumors of the anterior skull base. Eligible patients prospectively completed the Anterior Skull Base Surgery Questionnaire (ASBQ) and the 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaires in referring to 3 different periods throughout their treatment and recovery. Forty patients were included. The median volume coronal maximum length of the tumor was 3.6 cm (95% CI 2.7-4.1cm). Overall QoL significantly worsened at 1 month postoperatively but returned to baseline after 1 year. Unrelieved symptoms in specific domains prompted further evaluation of individual items. Transient worsening of taste (p=0.011) and olfaction (p=0.004) lasted for 1 month but gradually relieved within the first postoperative year, but vision consistently worsened over the course of the treatment (p=0.126). Age>50 years (p<0.001), comorbidities (p<0.001), tumor necrosis (p<0.001) and recurrence (p=0.001) were associated with worse preoperative QoL. Poor long-term QoL was noted in those undergoing adjuvant therapy (p=0.032). Overall ASBQ scores (p=0.024), subdomain scores in specific symptoms (p=0.016), and vision scores (p=0.009) were worse only in patients with the greater coronal maximum diameter at 1-month postoperatively. Greater coronal maximum diameter was related to worse preoperative subdomain scores regarding specific symptoms (p=0.030) and decreased postoperative long-term decreased vision scores (p=0.014). Long-term site-specific and sinonasal QoL eventually stabilized after EES. Greater coronal maximum diameter was significantly associated with worsened vision function. Temporarily worse olfactory, vision, and taste function may be tied to decreased short-term QoL.


In Vivo Cross-Linking and Co-Immunoprecipitation Procedure to Analyze Nuclear tRNA Export Complexes in Yeast Cells.
tRNAs are small noncoding RNAs that are predominantly known for their roles in protein synthesis and also participate in numerous other functions ranging from retroviral replication to apoptosis. In eukaryotic cells, all tRNAs move bidirectionally, shuttling between the nucleus and the cytoplasm. Bidirectional nuclear-cytoplasmic tRNA trafficking requires a complex set of conserved proteins. Here, we describe an in vivo biochemical methodology in Saccharomyces cerevisiae to assess the ability of proteins implicated in tRNA nuclear export to form nuclear export complexes with tRNAs. This method employs tagged putative tRNA nuclear exporter proteins and co-immunoprecipitation of tRNA-exporter complexes using antibody-conjugated magnetic beads. Because the interaction between nuclear exporters and tRNAs may be transient, this methodology employs strategies to effectively trap tRNA-protein complexes in vivo. This pull-down method can be used to verify and characterize candidate proteins and their potential interactors implicated in tRNA nuclear-cytoplasmic trafficking.


Serum response factor modulates neuron survival during peripheral axon injury.
The transcription factor SRF (serum response factor) mediates neuronal survival in vitro. However, data available so far suggest that SRF is largely dispensable for neuron survival during physiological brain function. Here, we demonstrate that upon neuronal injury, that is facial nerve transection, constitutively-active SRF-VP16 enhances motorneuron survival. SRF-VP16 suppressed active caspase 3 abundance in vitro and enhanced neuron survival upon camptothecin induced apoptosis. Following nerve fiber injury in vitro, SRF-VP16 improved survival of neurons and re-growth of severed neurites. Further, SRF-VP16 enhanced immune responses (that is microglia and T cell activation) associated with neuronal injury in vivo. Genome-wide transcriptomics identified target genes associated with axonal injury and modulated by SRF-VP16. In sum, this is a first report describing a neuronal injury-related survival function for SRF.


Values and limitations of duplex ultrasonography as the sole imaging method of preoperative evaluation for popliteal and infrapopliteal bypasses.
The purpose of this study was to evaluate whether duplex ultrasound arterial mapping (DAM) can reliably replace standard arteriography (SA) in the preoperative assessment of candidates for popliteal and infrapopliteal bypasses. This is the report of a two-phase study undertaken at our institution from July 1997 to May 1998. Carefully performed DAM averted the need for preoperative SA (51 of 58 procedures). The results of this study can be used as an impetus to initiate larger, multicenter protocols to further evaluate this newer noninvasive approach for patients presenting with severe lower-limb ischemia.


Uncertainty in contextual and kinematic cues jointly modulates motor resonance in primary motor cortex.
Contextual information accompanying others' actions modulates "motor resonance", i.e., neural activity within motor areas that is elicited by movement observation. One possibility is that we weigh and combine such information in a Bayesian manner according to their relative uncertainty. Therefore, contextual information becomes particularly useful when others' actions are difficult to discriminate. It is unclear, however, whether this uncertainty modulates the neural activity in primary motor cortex (M1) during movement observation. Here, we applied single-pulse transcranial magnetic stimulation (TMS) while subjects watched different grasping actions. We operationalized motor resonance as grip-specific modulation of corticomotor excitability measured in the index (FDI) versus the little finger abductor (ADM). We experimentally modulated either the availability of kinematic information ( experiment 1) or the reliability of contextual cues ( experiment 2). Our results indicate that even in the absence of movement kinematics, reliable contextual information is enough to trigger significant muscle-specific corticomotor excitability changes in M1, which are strongest when both kinematics and contextual information are available. These findings suggest that bottom-up mechanisms that activate motor representations as a function of the observed kinematics and top-down mechanisms that activate motor representations associated with arbitrary cues converge in M1. NEW & NOTEWORTHY Our study reveals new neurophysiological insights in support of the Bayesian account of action observation by showing that "motor resonance", i.e., neural activity evoked by observing others' actions, incorporates the uncertainty related to both contextual (prior beliefs) and kinematic (sensory evidence) cues. Notably, we show that muscle-specific modulation of M1 is strongest when context and movement kinematics are available, and it can be elicited even in the absence of movement kinematics.


Sexual experience and testosterone during adolescence alter adult neuronal morphology and behavior.
Steroid hormones released immediately before and after birth provoke sexual differentiation of neural circuits. Further, steroid hormones secreted during adolescence also exert long lasting effects on the nervous system. Hormones secreted during development may act through two distinct pathways: (1) hormones can directly affect neuron and synapse elimination and (2) endocrine changes in the nervous system may occur secondary to changes in social behaviors. Therefore, a critical period for organization of the nervous system by steroid hormones during adolescence may also be a sensitive period for the effects of social experience. The overall goal of this experiment was to determine whether the opportunity to mate with a sexually receptive female during this adolescent critical period would have enduring effects on behavior and neuronal morphology into adulthood. A second question was to determine the extent to which testosterone mediated the effects of these social interactions on adult outcomes. Compared to sexually inexperienced hamsters and those that experienced sex for the first time in adulthood, hamsters that experienced adolescent sexual experience displayed increased anxiety- and depressive-like behavioral responses. Adolescent sexual experiences decreased the complexity and length of dendrites on prefrontal cortical neurons and increased the expression of the pro-inflammatory cytokine interleukin 1β (IL-1β) in the PFC. In a second experiment, administration of testosterone during the adolescent period largely recapitulated the effects of adolescent sexual experience. These data support the overall hypothesis that a sensitive period extends into adolescence and that salient social stimuli during this time can significantly and persistently alter adult phenotype.