High levels of urinary eosinophil protein X in young asthmatic children predict persistent atopic asthma.
Levels of urinary eosinophil protein X (U-EPX) and eosinophil counts were measured in 32 children (12-36 months of age) who were hospitalized for acute asthma, and the U-EPX levels were measured in 20 healthy children of the same age. The ability of these parameters to predict persistent asthma (at least one wheezing episode during the last 6 months) and atopic asthma (a positive skin-prick test [SPT]), was evaluated at a follow-up 2 years later. On admission, levels of U-EPX were higher in children with asthma (median: 120 microg/mmol of creatinine; quartiles: 67-123 microg/mmol of creatinine) than in controls (60 microg/mmol of creatinine, 38-74 microg/mmol of creatinine; p< 0.001). The U-EPX level was higher in those with persistent atopic asthma at follow-up (173 microg/mmol of creatinine, 123-196 microg/mmol of creatinine, n = 16), than in those with persistent non-atopic asthma (73 microg/mmol creatinine, 46-105 microg/mmol of creatinine, n = 8; p< 0.05), and higher than in those with transient asthma (no symptoms at follow-up) (106 microg/mmol creatinine; 42-167 microg/mmol of creatinine, n = 8; p< 0.05). By multiple logistic regression analysis, U-EPX was the only parameter able to predict persistent atopic asthma; eosinophil counts, parental atopy, age or gender could not. Parental atopy was the only parameter predictive for persistent asthma, regardless of atopic status. In conclusion, levels of U-EPX, but not eosinophil counts, measured in young children hospitalized with acute asthma can predict the persistence of atopic asthma 2 years later.


The relationship between the chromophore moiety and the cation binding sites in bacteriorhodopsin.
Bleaching of the purple membrane strongly reduces the number of divalent cation binding sites as well as their affinities. Conversely, deionization of the bleached membrane drastically inhibits the chromophore regeneration. Proteolysis experiments using bromelain show that the bleached membrane has an additional cleavage site probably located at the fifth loop, whereas in the blue membrane, the C-terminal tail is no longer susceptible to proteolysis. It is suggested that there exists a close relationship between the retinal environment and one or more of the cation binding sites.


Techniques for improved delineation of normal anatomy of the upper abdomen and high retroperitoneum with gray-scale ultrasound.
Improved scanning techniques, positioning, and adjustments in instrumentation have been developed on the basis of more than 1,500 ultrasound examinations of the upper abdomen and high retroperitoneum. The latest instrumentation was employed, including gray-scale signal processing and focused transducers. These methods have resulted in improved visualization of normal anatomical structures, including the aorta, inferior vena cava, portal venous system, and major branches of these vessels as well as the common bile duct. Aspects of these techniques are illustrated and their applications and limitations in the differential diagnosis of upper abdominal disease are discussed.


Impact of healing touch with healing harp on inpatient acute care pain: a retrospective analysis.
This study examined the concomitant use of 2 complementary and alternative medicine modalities, Healing Harp and Healing Touch, to reduce pain, anxiety, and nausea in the postoperative patient population. The results demonstrate the effectiveness of using concomitant Healing Touch and Healing Harp to significantly reduce moderate to severe pain and anxiety in this patient population. Further research is warranted.


Substance P-like immunoreactivity in the trigeminal ganglion. A fluorescence, light and electron microscope study.
The trigeminal ganglion of rat and guinea pig was studied for the presence of immunoreactive substance-P using fluorescence, light and electronmicroscopy. In untreated animals substance P containing cells, with a diameter of 15 to 50 micron, were distributed throughout the ganglion and comprised 10-30% of all ganglion cells. Colchicine, injected intraventricularly to inhibit intra-axonal transport, had no effect on the number of substance P cells; but when the drug was injected directly into the posterior root of the ganglion, the proportion of these cells increased to as much as 50%. In the electron microscope, immunoreactive substance-P was confined to ganglion cells classified as B type according to the arrangement of subcellular organelles, and to unmyelinated nerve fibers. Subcellularly the immunoreactivity appeared in cytoplasmic vesicles, as well as dispersed in the nerve fibers and the perikarya of neurons. The great number of substance P immunoreactive ganglion cells suggests that they do not comprise a well defined subpopulation of the B-cells. However, the immunoreactivity was restricted to a distinct ultrastructural type of neurons with unmyelinated nerve fibers, suggesting that they also may share some distinct functions.


Pulmonary rehabilitation after total laryngectomy: a randomized cross-over clinical trial comparing two different heat and moisture exchangers (HMEs).
Post-laryngectomy heat and moisture exchanger (HME) use is known to have a beneficial effect on tracheal climate, pulmonary symptoms and related aspects. This study aims to investigate differences in clinical effects between the first and second generation Provox HMEs. The second generation (Provox XtraHME) has better humidification properties than the first generation (Provox HME), and has been shown to further improve tracheal climate. Forty-five laryngectomized patients, who were already using an HME, participated in a prospective, randomized cross-over clinical study in which each HME was used for 6 weeks. Results showed that for most parameters studied, the second generation HME performed equally well or better than the first generation HME. The improvement in tracheal climate translated into patients reporting significantly less tracheal dryness with the second generation than with the first generation (p = 0.039). Using an HME with better humidification properties is related to a reduction in tracheal dryness in our study population.


Statins and immune-mediated necrotizing myopathy: Variability in the risk.
Immune-mediated necrotizing myopathy (IMNM) is a form of statin myopathy characterized by the presence of antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti HMGCR). The aim of this study was to investigate the relationship between the different statins and the risk of IMNM. A two-time approach was used. First, we performed a descriptive analysis of the French national pharmacovigilance database (FNPV) for the period from 1985 to december2020. To identify relevant cases, we used Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PTs) related to IMNM. We performed a quantitative and qualitative review of individual case safety reports (ICSRs) recorded in the french vigilance spontaneous reporting system. In a second time, we performed a comparative analysis with the World Health Organization global individual case safety reports database (Vigibase). The association between IMNM and statins exposure was assessed by calculating the reporting odds ratio (ROR) and its 95% confidence interval. After analysis, a total of 25 ICSRs were related to IMNM in the FNPV. The suspected statins were atorvastatin (n=21), simvastatin (n=2), pravastatin (n=1) and rosuvastatin (n=1). In Vigibase, 567 notifications were identified. A significant ROR value was found for atorvastatin, pitavastatin, simvastatin, pravastatin and rosuvastatin. Atorvastatin presents the highest risk of IMNM. Our data suggest that the occurrence of IMNM is a class effect.


Transcription factors: switches for regulating growth and development in macrofungi.
Macrofungi (or mushrooms) act as an extraordinarily important part to human health due to their nutritional and/or medicinal value, but the detailed researches in growth and development mechanisms have yet to be explored further. Transcription factors (TFs) play indispensable roles in signal transduction and affect growth, development, and metabolism of macrofungi. In recent years, increasing research effort has been employed to probe the relationship between the development of macrofungi and TFs. Herein, the present review comprehensively summarized the functional TFs researched in macrofungi, including modulating mycelial growth, fructification, sclerotial formation, sexual reproduction, spore formation, and secondary metabolism. Meanwhile, the possible effect mechanisms of TFs on the growth and development of some macrofungi were also revealed. Specific examples of functional characterizations of TFs in macrofungi (such as Schizophyllum commune and Coprinopsis cinerea) were described to a better comprehension of regulatory effect. Future research prospects in the field of TFs of macrofungi are discussed. We illustrated the functional versatility of the TFs in macrofungi based on specific examples. A systematical realization of the interaction and possible mechanisms between TFs and macrofungi can supply possible solutions to regulate genetic characteristics, which supply novel insights into the regulation of growth, development and metabolism of macrofungi. KEY POINTS: • The functional TFs researched in macrofungi were summarized. • The possible effect mechanisms of TFs in macrofungal were described. • The multiple physiological functions of TFs in macrofungi were discussed.


Plasma microparticles of intubated COVID-19 patients cause endothelial cell death, neutrophil adhesion and netosis, in a phosphatidylserine-dependent manner.
COVID-19 has compelled scientists to better describe its pathophysiology to find new therapeutic approaches. While risk factors, such as older age, obesity, and diabetes mellitus, suggest a central role of endothelial cells (ECs), autopsies have revealed clots in the pulmonary microvasculature that are rich in neutrophils and DNA traps produced by these cells, called neutrophil extracellular traps (NETs.) Submicron extracellular vesicles, called microparticles (MPs), are described in several diseases as being involved in pro-inflammatory pathways. Therefore, in this study, we analyzed three patient groups: one for which intubation was not necessary, an intubated group, and one group after extubation. In the most severe group, the intubated group, platelet-derived MPs and endothelial cell (EC)-derived MPs exhibited increased concentration and size, when compared to uninfected controls. MPs of intubated COVID-19 patients triggered EC death and overexpression of two adhesion molecules: P-selectin and vascular cell adhesion molecule-1 (VCAM-1). Strikingly, neutrophil adhesion and NET production were increased following incubation with these ECs. Importantly, we also found that preincubation of these COVID-19 MPs with the phosphatidylserine capping endogenous protein, annexin A5, abolished cytotoxicity, P-selectin and VCAM-1 induction, all like increases in neutrophil adhesion and NET release. Taken together, our results reveal that MPs play a key role in COVID-19 pathophysiology and point to a potential therapeutic: annexin A5.


Left hemispheric dominance of vestibular processing indicates lateralization of cortical functions in rats.
Lateralization of cortical functions such as speech dominance, handedness and processing of vestibular information are present not only in humans but also in ontogenetic older species, e.g. rats. In human functional imaging studies, the processing of vestibular information was found to be correlated with the hemispherical dominance as determined by the handedness. It is located mainly within the right hemisphere in right handers and within the left hemisphere in left handers. Since dominance of vestibular processing is unknown in animals, our aim was to study the lateralization of cortical processing in a functional imaging study applying small-animal positron emission tomography (microPET) and galvanic vestibular stimulation in an in vivo rat model. The cortical and subcortical network processing vestibular information could be demonstrated and correlated with data from other animal studies. By calculating a lateralization index as well as flipped region of interest analyses, we found that the vestibular processing in rats follows a strong left hemispheric dominance independent from the "handedness" of the animals. These findings support the idea of an early hemispheric specialization of vestibular cortical functions in ontogenetic older species.


Efficient electroreduction of CO to acetate using a metal-azolate framework with dicopper active sites.
Electrochemical reduction of CO to value-added products, especially C2 products, provides a potential approach to achieve carbon neutrality and overcome the energy crisis. Herein, we report a metal-azolate framework (CuBpz) with dicopper active sites as an electrocatalyst for the electrochemical CO reduction reaction (eCORR). As a result, CuBpz achieved an impressive faradaic efficiency (FE) of 47.8% for yielding acetate with a current density of -200 mA cm-2, while no obvious degradation was observed over 60 hours of continuous operation at a current density of -200 mA cm-2. Mechanism studies revealed that the dicopper site can promote C-C coupling between two C1 intermediates, thereby being conducive to the generation of the key *CH2COOH intermediate.


Educational clinical supervision: meeting the needs of specialist community practitioner students and professional practice.
In light of the possible demise of the community practice teacher, this paper proposes that a specific system of educationally led clinical supervision would benefit learning, teaching and assessing in the practice elements of specialist community practitioner education. Such a system would be additional to models of clinical supervision currently utilized in practice. An educative supervisory relationship would foster those skills and attributes essential for specialist community practice, enabling students to move toward mature responsible practice. It would provide experience of supportive frameworks that could be later utilized in professional practice. Clinical supervision specifically tailored for specialist community practitioner education would enable equity across branches and could be delivered in a variety of settings without a supervisor having to be 'on-site', thus benefiting comparatively isolated students in practice nursing and occupational health. To work successfully, educationally led clinical supervision necessitates a joint response by educational institutions and those practices where specialist community students undertake assessed placements. Without such a system in place to support specialist community practitioner courses, the standard of education and future practice cannot be assured.


[Clinical research on effects of shenfu injection in different dosage in preventing heart failure occurred in patients of acute myocardial infarction with elevated ST segment].
To study the preventive effect of Shenfu Injection (SI) in different dosage on occurrence of heart failure in patients of acute myocardial infarction (MI) with elevated ST segment. Ninety-seven patients of MI were divided into 3 groups, all were treated with conventional therapy, but to the SI treated groups, intravenous injection of low (0.3 ml/kg) or high dose (0.6 ml/kg) of SI were given once a day additionally. After 14 days' treatment, the incidence of heart failure and its severity were observed and evaluated with Killip grading. There was no significant difference in the incidence of heart failure among the 3 groups, but the severity of heart failure in the SI treated groups was remarkably milder than that in the control group, and the high dose SI showed the effect superior to that of low dose SI. Based on the conventional treatment, Shenfu Injection is helpful for alleviating the severity of heart failure.


Arsenic accumulation in irrigated agricultural soils in Northern Greece.
The accumulation of arsenic in soils and food crops due to the use of arsenic contaminated groundwater for irrigation has created worldwide concern. In the Chalkidiki prefecture in Northern Greece, groundwater As reach levels above 1000μg/L within the Nea Triglia geothermal area. While this groundwater is no longer used for drinking, it represents the sole source for irrigation. This paper provides a first assessment of the spatial extent of As accumulation and of As mobility during rainfall and irrigation periods. Arsenic content in sampled soils ranged from 20 to 513mg/kg inside to 5-66mg/kg outside the geothermal area. Around irrigation sprinklers, high As concentrations extended horizontally to distances of at least 1.5m, and to 50cm in depth. During simulated rain events in soil columns (pH=5, 0μg As/L), accumulated As was quite mobile, resulting in porewater As concentrations of 500-1500μg/L and exposing plant roots to high As(V) concentrations. In experiments with irrigation water (pH=7.5, 1500μg As/L), As was strongly retained (50.5-99.5%) by the majority of the soils. Uncontaminated soils (<30mg As/kg) kept soil porewater As concentrations to below 50μg/L. An estimated retardation factor R(f)=434 for weakly contaminated soil (<100mg/kg) indicates good ability to reduce As mobility. Highly contaminated soils (>500mg/kg) could not retain any of the added As. Invoked mechanisms affecting As mobility in those soils were adsorption on solid phases such as Fe/Mn-phases and As co-precipitation with Ca. Low As accumulation was found in collected olives (0.3-25μg/kg in flesh and 0.3-5.6μg/kg in pits). However, soil arsenic concentrations are frequently elevated to far above recommended levels and arsenic uptake in faster growing plants has to be assessed.


The effects of human interferon-alpha upon in vitro canine immune responses.
The effects of varying amounts (100.0-0.01 units/ml) of human interferon (IFN) alpha upon in vitro canine immune responses were studied. Exogenous heterologous species IFN-alpha suppressed B-cell differentiation in a dose-dependent fashion and enhanced interleukin-2 production (P less than 0.05) by activated T-lymphocytes. Interferon enhanced natural killer (NK) cytotoxicity when tested against NK-resistant target cells (less than 0.05). One hundred units IFN/ml increased interleukin-1 production by canine monocytes, but this effect was not statistically significant. Exogenous IFN had no discernible effect upon lectin-induced lymphocyte blastogenesis. The results of this study demonstrate that human IFN-alpha does affect various canine lymphocyte functions and these effects depend upon the in vitro assay system employed.


The protective value of vaccine-induced neutralising antibody titres in swine fever.
The relationship between vaccine-induced antibody titres against swine fever virus (SFV), as measured by the neutralisation peroxidase-linked assay (NPLA), and protection against virus multiplication, excretion and transmission, disease and death was studied in 46 pigs. The pigs were housed individually and challenged intranasally with 100 pig ID50 of the virulent Brescia strain of SFV. In order to detect virus transmission, a swine fever (SF)-susceptible sentinel pig was placed in contact with the vaccinated animal 2 days after challenge. All 11 pigs with pre-challenge NPLA titres less than 12.5 responded to the challenge with fever, 8 out of 10 showed leucopenia, 7 transmitted virus to their contact and 3 died. Of the 9 animals with titres greater than or equal to 12.5 and less than 25, 8 developed fever, 6 out of 7 had leucopenia, 2 excreted and/or transmitted virus and all survived. Of the 12 pigs with pre-challenge titres greater than or equal to 25 and less than 50, 5 responded with fever, 6 out of 10 had leucopenia, 4 excreted virus and none died. Although all pigs with prechallenge titres greater than or equal to 50 showed a booster response, virus transmission was not observed, indicating that in the case of exposure such animals would not contribute towards the spread of field virus. From an epidemiological point of view, titres less than 32 were found inadequate.


Effect of heat stress on brain 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in some vertebrate species.
1. The variations in 5-HT and 5-HIAA levels following heat exposure and split heat doses were determined in the different brain regions of Gerbillus pyramidum, Streptopelia senegalensis aegyptiaca and Agama stellio. 2. Heat exposure was found to be associated with an increase in the levels of the two indole compounds. 3. The 5-HT concentrations increased markedly in the three species following the first heat dose and decreased following the second dose in the various brain regions except in the cerebellum of Agama. 4. The increased 5-HT levels when animals are exposed to high temperature probably represent a response to activate heat-loss mechanisms and to depress heat production.


Efficacy and safety of percutaneous computed tomography-guided high-dose-rate interstitial brachytherapy in treatment of oligometastatic lymph node metastases of retroperitoneal space.
To assess efficacy, safety, and outcome of computed tomography (CT)-guided high-dose-rate (HDR) interstitial brachytherapy in patients with oligometastatic lymph node metastases of the retroperitoneal space. 24 patients with a total of 47 retroperitoneal lymph node metastases from different primary tumors were treated with CT-guided interstitial brachytherapy using an 192Ir source (single fraction irradiation). Every three months after treatment, clinical and imaging follow-up were conducted to evaluate local control and safety. Median follow-up was 9.6 months (range, 2.9-39.0 months). Local tumor control rate was 95.7%. The median diameter of the gross tumor volume was 2.2 cm (range, 1-8.6 cm), treated with a median D100 (minimal enclosing tumor dose) of 14.9 Gy (range, 4.5-20.6 Gy). One severe adverse event (grade three) was recorded.Cumulative median progression-free survival was 4.2 months (range, 1.4-23.7 months), and cumulative median overall survival after interstitial brachytherapy was 15.9 months (range, 3.8-39.0 months). CT-guided HDR interstitial brachytherapy is a safe and feasible method for local ablation of oligometastatic lymph node metastases of the retroperitoneal space, and might provide a well-tolerated additional therapeutic option in the multidisciplinary management of selected patients.


Coherence scanning interferometry allows accurate characterization of micrometric spherical particles contained in complex media.
Characterizing very small particles, from a few dozen micrometers to the nanometric scale, is a very challenging application in a wide range of domains. In this work, we demonstrate, through the recovery of silica and polystyrene bead properties (i.e. their size and refractive index) that Coherence Scanning Interferometry (CSI), in addition of being contactless, non-destructive, label-free and very well spatially resolved, is a very interesting and promising tool for such complex characterization. The CSI system is used as an imaging Fourier transform spectrometer meaning that the characterizations are achieved by analyzing the interference signal in the spectral domain. Some simulations of the proposed technique are presented and show that the accuracy of such characterization, in particular the measurement of the refractive index, are closely related to the signal to noise ratio. This observation is thereafter confirmed by the experimental results of beads buried within the depth of a transparent sample. Finally, the method is theoretically tested in the case of a scattering medium in which the quality of the signal is highly degraded. In this context, a geometrical approach enabling the simulation of an interference signal from a scattering layer is first proposed and then validated by means of comparison with experimental data.


Dissociative Trait as a Mediator of Problematic Internet Use in Children with attention-deficit/hyperactivity Disorder and Learning Disabilities.
This study used data from a national birth cohort study to investigate the duration of internet use at the age of 12 years among children diagnosed with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disabilities (IDs) and learning disabilities (LDs) at the age of five and a half years (66 months) to understand whether an ADHD, ASD, ID and LD diagnosis in childhood increases the risk of problematic internet use (PIU) in adolescence. Furthermore, the pathway relationship of dissociative absorptive trait with PIU and these diagnoses was also investigated. The 5.5- and 12-year-old Taiwan Birth Cohort Study dataset was used (N = 17,694). More boys were diagnosed with LDs, IDs, ADHD and ASD; however, girls were at increased likelihood of PIU. ID and ASD diagnoses were not associated with increasing PIU likelihood. However, children who had been diagnosed with LDs and ADHD, along with higher dissociative absorptive trait, had an indirectly increased likelihood of PIU in adolescence. Dissociative absorption was found to be a mediating factor between childhood diagnosis and PIU and can be used as a screening indicator in prevention programs to reduce the duration and severity of PIU in children diagnosed with ADHD and LDs. Furthermore, with the increased prevalence of smartphone usage in adolescents, education policy-makers should pay greater attention to the issue of PIU in female adolescents.


Measurement of respiratory mechanics using the Puritan-Bennett 7200a ventilator.
This study was designed in order to validate the respiratory mechanical variables measured by the Puritan-Bennett 7200a ventilator equipped with the 30/40 module. Two ventilators were connected to a lung model and submitted to several breathing patterns by modifying the respiratory rate, the tidal volume, the inspiratory flow-rate and the model resistance. The inspiratory flow-rate (V), tidal volume (VT), peak inspiratory pressure (Pmax), plateau pressure (Pplat) and PEEP measured by the ventilators were compared with the same variables measured at the connection between the breathing circuit and the lung model. The compliance (C30/40) and the resistance (R30/40) calculated by the 30/40 module were compared with those calculated by using the variables measured by the reference equipment. Both ventilators made a constant underestimation of V by 2.8 and 3.7 L.min-1, respectively. The VT was measured with a mean error of less than 10 ml but did not reflect the preselected values in the presence of an intrinsic PEEP. The Pplat was overestimated by 7 and 10%, respectively. The same calibration error was observed with Pmax which was also affected by a pressure gradient due to the resistance of the breathing circuit. Even in the absence of intrinsic PEEP, C30/40 presented an error due to the combination of the measurement errors on VT, Pplat and PEEP. Finally, R30/40 presented a high percentage of error due to the combination of the measurement errors on V, Pmax, and Pplat, and to a sporadic aberrant selection of V. Due to these numerous sources of error, the two ventilators studied did not give reliable estimates of resistance and compliance.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification in CLL of circulating intraclonal subgroups with varying B-cell receptor expression and function.
Chronic lymphocytic leukemia (CLL) is a tumor of circulating B cells, variably stimulated and anergized following exposure to antigen in lymphoid tissues. Down-modulation of surface IgM (sIgM) occurs, but expression and signal capacity can recover in vitro and apparently in vivo during recirculation. We have now dissected individual circulating clones of CLL cases according to sIgM expression level by differential binding to bead-bound anti-IgM. Four clear subgroups (SG1-4) with increasing sIgM were identified in 37/37 cases. Engagement of sIgM induced phosphorylation of PLCγ2 and ERK1/2 at levels ranging from very low in SG1 to high in SG4. Phosphorylation was suppressed by the BTK inhibitor ibrutinib. Expression of CXCR4 also increased from SG1 to SG4, but markers of previous activation and proliferation were dominant in SG1. Incubation of whole CLL populations in vitro led to striking increases in CXCR4 expression as well as recovery of sIgM. Clonal analysis reveals dynamic SGs following presumed antigen stimulation in tissues. SG4 represents a fully recovered, potentially dangerous population equipped to migrate to tissue and receive a proliferative stimulus. SG1 likely represents a postmitotic unresponsive "resting" population. The effect of ibrutinib on the small SG4 population may be the critical factor in therapeutic success.


What ultrasonography can tell in breast masses that mammography and physical examination cannot.
The capability of ultrasonography to provide additional information to the physical and mammographic examination for therapeutic decision was investigated in a prospective study. Four hundred patients with palpable or radiologic breast masses requiring surgical biopsy were studied. The high resolution and accuracy of ultrasonography vs. mammography in the diagnosis of cystic masses (96%, 63/66 vs. 42%, 20/48) (p less than 0.001) and fibrocystic masses (84%, 131/156 vs. 74%, 80/108) (p less than 0.10), led to a substantial reduction of surgical biopsies in favor of aspiration or follow-up policy, particularly when physical examination and mammography were inconclusive. Breast cancers were accurately diagnosed in 73% (88/120) by sonography and 84% (98/116) by mammography (p greater than 0.10). The major limitation of ultrasonography was noticed in the diagnosis of minimal breast cancer (23%, 5/21) due to its inability to visualize microcalcifications. Our study validates the importance of ultrasonography in the diagnosis and therapeutic decision of cystic and fibrocystic masses but cannot substitute mammography in early detection of breast carcinoma.


Thalamic glutamate/glutamine in restless legs syndrome: increased and related to disturbed sleep.
To evaluate possible abnormal increase in thalamic glutamate/glutamine levels for restless legs syndrome (RLS) indicating increased glutamatergic activity producing arousal that at night disrupts and shortens sleep. (1)H MRS of the right thalamus was performed using a 1.5 T GE MRI scanner and the PROBE-P (PRESS) on 28 patients with RLS and 20 matched controls. The Glx signal (combination of mostly glutamate [Glu] and glutamine [Gln]) was assessed as a ratio to the total creatine (Cr). This study tested 2 primary hypotheses: 1) higher thalamic Glx/Cr for patients with RLS than controls; 2) thalamic Glx/Cr correlates with increased wake during the sleep period. The Glx/Cr was higher for patients with RLS than controls (mean ± SD 1.20 ± 0.73 vs 0.80 ± 0.39, t = 2.2, p = 0.016) and correlated significantly with the wake time during the sleep period (r = 0.61, p = 0.007) and all other RLS-related polysomnographic sleep variables (p < 0.05) except for periodic leg movements during sleep (PLMS)/hour. The primary findings introduce 2 new related dimensions to RLS: abnormalities in a major nondopaminergic neurologic system and the arousal disturbance of sleep. The strong relation of the arousal sleep disturbance to glutamate and the lack of relation to the PLMS motor features of RLS contrasts with the reverse for dopamine of a limited relation to arousal sleep disturbance but strong relation to PLMS. Understanding this dichotomy and the interaction of these 2 differing systems may be important for understanding RLS neurobiology and developing better treatments for RLS.


Linked Nickel Metallacrowns from a Phosphonate/2-Pyridyloximate Blend of Ligands: Structure and Magnetic Properties.
In the present work, four new Ni(II) clusters with nuclearities ranging between Ni4 and Na2Ni8 were synthesized, employing the versatile ligand phenylphosphonate and 6-methylpyridylaldoximate as the coligand. Crystallographic data show that the tetranuclear complex [Ni4(6-MepaoH)4(PhPO3)2(OH)2(MeOH)4](OH)2 (1) consists of two dimers linked by phosphonate bridges, whereas [Cs2Ni6(6-Mepao)6(PhPO3)3(OH)2(H2O)8] (2), Cs[Ni8(6-MepaoH)6(6-Mepao)6(PhPO3)3](ClO4)5 (3), and [Ni8Na2(BzO)6(6-Mepao)6(PhPO3)3] (4) are built from phosphonato-linked {Ni3(6-Mepao)3} metallacycles. The [9-MC(Ni(II)(6-Mepao))-3] fragments in 2-4 show the unusual coordination of additional Cs(+), Na(+), and/or Ni(II) cations. Direct-current magnetic measurements were carried in the 300-2 K range. Analysis of the experimental data revealed a complex response with strong antiferromagnetic interactions mediated by the oximato bridges and weak interactions mediated by the phosphonate ones.


Deterministic Whole-Genome Amplification of Single Cells.
This chapter describes a single-cell whole genome amplification method (WGA) that has been originally published under the name "Single Cell Comparative Genomic Hybridization (SCOMP)" (Klein et al., Proc Natl Acad Sci U S A 96(8):4494-4499, 1999). The method has recently become available commercially under the name "Ampli1(™) WGA Kit." It is a PCR-based technique for whole genome amplification (WGA) allowing comprehensive and quite uniform amplification of DNA from low quantities of input DNA material, in particular single cells. The method is based on a ligation-mediated adaptor linker PCR approach. In contrast to other PCR-based WGA approaches, both the primer design and mechanism underlying the fragmentation of genome are nonrandom, enabling high priming efficiency and deterministic fragmentation of template DNA. This is particularly important for the design of (diagnostic) assays targeting specific loci. Here, we describe the WGA protocol for amplification of single-cell genomes designed to provide high-quality material in quantity sufficient for a number of locus-specific and genome-wide downstream assays [e.g., targeted Sanger sequencing, restriction fragment length polymorphism (RFLP), quantitative PCR (qPCR), and array comparative genomic hybridization (CGH)].


Nephrology in Africa--not yet uhuru.
Nephrology is a 'Cinderella speciality', a disregarded area of health care, in Africa. Other health issues have relegated the treatment of kidney diseases to a low priority status, and the cost of treating the more common and widespread communicable diseases, financial mismanagement and corruption in many countries has sounded the death knell for expensive therapies such as dialysis. The communicable diseases that have devastated the health systems around Africa are tuberculosis and HIV/AIDS. Until recently, very little information was available on the impact of HIV on acute and chronic dialysis admissions. Patients with acute kidney injury (AKI) in most of Africa are seldom treated because of great distances to travel, lack of expertise, poverty and poor sustainable funding for health matters. An acute peritoneal dialysis (PD) programme has now been initiated in Tanzania but the sustainability of this project will be tested in the future. The International Society of Nephrology (ISN) has developed a training programme for nephrologists from developing countries, which may now be bearing fruit. A report from the sub-Saharan Africa region shows that the numbers of patients on dialysis and those diagnosed with chronic kidney disease (CKD) has increased significantly. Other ISN-sponsored programmes such as Continuing Medical Education activities for physicians and community screening projects have had far-reaching positive effects. Government funding for a dialysis programme is well established in South Africa, but this funding is limited so that the numbers accepted for public dialysis are restricted. Consequently in the Western Cape province of South Africa, a 'category system' has been formulated to attempt to cope with this unacceptable and restrictive ruling.


Structural study of four-stranded quadruplex structures containing 2'-deoxy-8-(propyn-1-yl)adenosine.
In this paper, we report the NMR structural study of two quadruplex structures formed by truncations of the human telomeric sequence and containing a modified base, namely d(AprGGGT) and d(TAprGGGT), where Apr indicates 2'-deoxy-8-(propyn-1-yl)adenosines. Both oligonucleotides have been found to form 4-fold symmetric G-quadruplex structures with all strands parallel and equivalent to each other and characterized by higher thermal stabilities than the natural counterparts. The presence of the propynyl groups affects the conformations of the 5' edge of both quadruplexes in such a way to prevent the formation of one of the two possible H-bond patterns observed for a canonical A-tetrad. The increased thermal stabilities of the modified quadruplexes seem to be mostly due to a prevalent syn glycosidic conformation assumed by the Apr residues.


Comparative genet survival after fire in woody Mediterranean species.
Using data from three fires in northeastern Spain, we tested a condition necessary to support the idea that fire has been a factor in the evolution of the resprouting habit: populations of all resprouting species within a community should show high levels of genet survival after fires and show a low coefficient of variation. Species with high mean survival values were:Quercus ilex L.,Phillyrea latifolia L., andViburnum tinus L., with 88, 86 and 83% survival respectively; these groups had resprouts emerging from rootcrowns. Then followedArbutus unedo L. (75%),Pistacia lentiscus L. (73%),Erica arborea L. (77%),Erica multiflora L. (57%) andJuniperus oxycedrus L. (55%). This last group had resprouts from lignotubers or burls. These two groups also differed in the variability around the mean: the first showed a lower coefficient of variation, 6-12, and the second ranged from 19 to 26. Slope exposure had no significant influence on the process of resprouting, but soil depth did, with precipitation as a covariate. In the shallow soil category, the difference in genet survival between southern and northern exposures was 14% (71% vs. 57%); while the difference in the deep soil category was low, 5% (87% vs. 82%). There was no significant interaction. The component of variance for soils was larger than that for species-specific effects; substantial overlap of the within-species variance indicated that species responded as if they were a single hypothetical population, in which most of the variation in chances of survival was due to the soil conditions. The possession of the resprouting habit did not ensure a high performance. Hence, we find weak support for fire as a factor in the evolution of the resprouting habit.


Superheated emulsion in neutron spectrometry.
The application of superheated emulsion as a neutron spectrometer is described by varying the operating temperature and the ambient pressure of the emulsion. For the calibration of the detector, a relationship was established between the degree of metastability (ss) of superheated emulsion and the threshold neutron energy. The sensitivity and the integral response of the emulsion was calculated and compared with the experimental results.


Improving the usability and archival stability of bioinformatics software.
Implementation of bioinformatics software involves numerous unique challenges; a rigorous standardized approach is needed to examine software tools prior to their publication.


The expanding world of small molecule microarrays.
Speed and throughput are vital ingredients for discovery-driven, "-omics" research. The small molecule microarray is one such platform, which delivers phenomenal screening throughput and capabilities. The concept at the heart of the technology is elegant, yet simple: by presenting large collections of molecules at a high density on a flat surface, one is able to interrogate them quickly and conveniently, evaluating all possible interactions in a single step. SMMs have, over the last decade, been established as a robust platform for screening, lead discovery, and molecular characterization. In this chapter, we describe the ways in which microarrays have been constructed and applied, focusing on the practical challenges faced when designing and performing SMM experiments. This is written as an introduction for new readers to the field, explaining the key principles and laying the foundation for the chapters that follow.


A pilot study of bevacizumab-based therapy in patients with newly diagnosed high-grade gliomas and diffuse intrinsic pontine gliomas.
Although bevacizumab has not proven effective in adults with newly diagnosed high-grade gliomas (HGG), feasibility in newly diagnosed children with diffuse intrinsic pontine gliomas (DIPG) or HGG has not been reported in a prospective study. In a safety and feasibility study, children and young adults with newly diagnosed HGG received radiotherapy (RT) with bevacizumab (10 mg/kg: days 22, 36) and temozolomide (75-90 mg/m(2)/day for 42 days) followed by bevacizumab (10 mg/kg, days 1, 15), irinotecan (125 mg/m(2), days 1, 15) and temozolomide (150 mg/m(2)/day days 1-5). DIPG patients did not receive temozolomide. Telomerase activity, quality of life (QOL), and functional outcomes were assessed. Among 27 eligible patients (15 DIPG, 12 HGG), median age 10 years (range 3-29 years), 6 discontinued therapy for toxicity: 2 during RT (grade 4 thrombocytopenia, grade 3 hepatotoxicity) and 4 during maintenance therapy (grade 3: thrombosis, hypertension, skin ulceration, and wound dehiscence). Commonest ≥grade 3 toxicities included lymphopenia, neutropenia and leukopenia. Grade 3 hypertension occurred in 2 patients. No intracranial hemorrhages occurred. For DIPG patients, median overall survival (OS) was 10.4 months. For HGG patients, 3-year progression free survival and OS were 33 % (SE ± 14 %) and 50 % (SE ± 14 %), respectively. All 3 tested tumor samples, demonstrated histone H3.3K27M (n = 2 DIPG) or G34R (n = 1 HGG) mutations. QOL scores improved over the course of therapy. A bevacizumab-based regimen is feasible and tolerable in newly diagnosed children and young adults with HGG and DIPG.


Reactions in rat gluteal muscle to titanium implants.
A new approach to the analysis of tissue-implant interaction is presented using rat gluteal muscle as implantation site and using monoclonal antibodies to identify and quantify cells around the implant. The method can be used for comparative studies on biocompatibility. In this methodological investigation, pure titanium (Ti) was studied, revealing an initial response of macrophages, followed by the formation of a fibrous membrane, in which, even at 50 and 70 d, la-expressing cells and suppressor T-lymphocytes were present.


Integration of QSAR models for bioconcentration suitable for REACH.
QSAR (Quantitative Structure Activity Relationship) models can be a valuable alternative method to replace or reduce animal test required by REACH. In particular, some endpoints such as bioconcentration factor (BCF) are easier to predict and many useful models have been already developed. In this paper we describe how to integrate two popular BCF models to obtain more reliable predictions. In particular, the herein presented integrated model relies on the predictions of two among the most used BCF models (CAESAR and Meylan), together with the Applicability Domain Index (ADI) provided by the software VEGA. Using a set of simple rules, the integrated model selects the most reliable and conservative predictions and discards possible outliers. In this way, for the prediction of the 851 compounds included in the ANTARES BCF dataset, the integrated model discloses a R(2) (coefficient of determination) of 0.80, a RMSE (Root Mean Square Error) of 0.61 log units and a sensitivity of 76%, with a considerable improvement in respect to the CAESAR (R(2)=0.63; RMSE=0.84 log units; sensitivity 55%) and Meylan (R(2)=0.66; RMSE=0.77 log units; sensitivity 65%) without discarding too many predictions (118 out of 851). Importantly, considering solely the compounds within the new integrated ADI, the R(2) increased to 0.92, and the sensitivity to 85%, with a RMSE of 0.44 log units. Finally, the use of properly set safety thresholds applied for monitoring the so called "suspicious" compounds, which are those chemicals predicted in proximity of the border normally accepted to discern non-bioaccumulative from bioaccumulative substances, permitted to obtain an integrated model with sensitivity equal to 100%.


Verapamil prevents the development of alcoholic dysfunction in hamster myocardium.
Ethanol causes depression of cardiac function. A new model in hamsters was developed for studying ethanol-induced myocardial dysfunction and the effects of verapamil in preventing the functional and metabolic derangements caused by ethanol ingestion were evaluated. Ethanol was added to the drinking water of hamsters in increasing amounts, reaching 50% from 5 weeks on. A control group received plain water only. A third group had verapamil (1.75 mg/cc) added to the ethanol-water mixture to evaluate its potential protective effect. After 5, 7 and 12 weeks, the animals were killed and the hearts perfused using a Langendorff heart preparation. Pressures were recorded and metabolic analysis was performed by the freeze-clamp technique. Compared with control hearts, the hearts from hamsters ingesting ethanol showed significant depression of developed pressure and maximal rate of rise in pressure. There was also significant depression of high energy phosphates and adenosine. The animals drinking the ethanol-verapamil mixture had preservation of left ventricular performance and high energy phosphates, with measurements indistinguishable from those of the control group. In summary, verapamil prevented the development of myocardial depression and preserved normal energy metabolism in hearts of hamsters drinking 50% ethanol.


Circadian Dysfunction in Adipose Tissue: Chronotherapy in Metabolic Diseases.
Essential for survival and reproduction, the circadian timing system (CTS) regulates adaptation to cyclical changes such as the light/dark cycle, temperature change, and food availability. The regulation of energy homeostasis possesses rhythmic properties that correspond to constantly fluctuating needs for energy production and consumption. Adipose tissue is mainly responsible for energy storage and, thus, operates as one of the principal components of energy homeostasis regulation. In accordance with its roles in energy homeostasis, alterations in adipose tissue's physiological processes are associated with numerous pathologies, such as obesity and type 2 diabetes. These alterations also include changes in circadian rhythm. In the current review, we aim to summarize the current knowledge regarding the circadian rhythmicity of adipogenesis, lipolysis, adipokine secretion, browning, and non-shivering thermogenesis in adipose tissue and to evaluate possible links between those alterations and metabolic diseases. Based on this evaluation, potential therapeutic approaches, as well as clock genes as potential therapeutic targets, are also discussed in the context of chronotherapy.


Dissociation of motor maturation.
We prospectively acquired clinical data regarding the presentation, evaluation, and developmental progress of all patients identified with dissociated motor maturation to define their clinical outcomes. Children (N = 8) referred for evaluation of suspected cerebral palsy because of delayed sitting or walking and identified to have dissociated motor maturation were followed with serial clinical examination. All displayed the characteristic "sitting on air" posture while held in vertical suspension and had otherwise normal developmental assessments. This posture is composed of the hips held in flexion and abduction with the knees extended and feet plantar or dorsiflexed. Three children were initially evaluated at 10 months of age owing to absence of sitting and five other children were evaluated at a mean of 14 months (range 12-19 months) owing to inability to stand. Follow-up evaluations were conducted over a mean of 10.5 months (range 5-34 months). Five children were born prematurely at 34 to 36 weeks gestation. Denver Developmental Screening Test and general and neurologic examinations were normal except to note hypotonia in six children and the "sitting on air" posture in all of the children. Four children have older siblings or parents who "walked late" (after 15 months). On average, the children attained sitting by 8 months (range 7-10 months). One child did not crawl prior to independent walking, two children scooted rather than crawled, and five children crawled at an average of 13.5 months (range 10-16 months). All children cruised by a mean of 18 months (range 16-21.5 months) and attained independent walking by 20.1 months (range 18-25 months). Neuroimaging and serum creatine kinase enzyme testing were normal in two children who were tested. These eight children conform to the syndrome of dissociated motor maturation. The "sitting on air" posture serves as a diagnostic sign and anticipated excellent prognosis, but follow-up is required to ensure a normal outcome.


Circulating secretory phospholipase A2 activity predicts recurrent events in patients with severe acute coronary syndromes.
The purpose of this study was to determine the prognostic value of circulating secretory phospholipase A2 (sPLA2) activity in patients with acute coronary syndromes (ACS). The plasma level of type IIA sPLA2 is a risk factor for coronary artery disease (CAD) and is associated with adverse outcomes in patients with stable CAD. The prognostic impact of sPLA2 in patients with ACS is unknown. Secretory phospholipase A2 antigen levels and activity were measured in plasma samples of 446 patients with ACS, obtained at the time of enrollment. Baseline sPLA2 activity was associated with the risk of death and myocardial infarction (MI). The unadjusted rate of death and MI increased in a stepwise fashion with increasing tertiles of sPLA2 activity (p < 0.0001). The association remained significant in the subgroup of patients who had MI with ST-segment elevation (p = 0.014) and the subgroup of patients who had unstable angina or non-ST-segment elevation MI (p < 0.002). After adjustment for clinical and biological variables, the hazard ratios for the combined end point of death or MI in the third tertile of sPLA2 compared with the first and second tertiles was 3.08 (95% confidence interval, 1.37 to 6.91, p = 0.006). A single measurement of plasma sPLA2 activity at the time of enrollment provides strong independent information to predict recurrent events in patients with ACS.


Inequality in quality-adjusted life expectancy by educational attainment in Norway: an observational study.
Health inequalities are often assessed in terms of life expectancy or health-related quality of life (HRQoL). Few studies combine both aspects into quality-adjusted life expectancy (QALE) to derive comprehensive estimates of lifetime health inequality. Furthermore, little is known about the sensitivity of estimated inequalities in QALE to different sources of HRQoL information. This study assesses inequalities in QALE by educational attainment in Norway using two different measures of HRQoL. We combine full population life tables from Statistics Norway with survey data from the Tromsø study, a representative sample of the Norwegian population aged ≥ 40. HRQoL is measured using the EQ-5D-5L and EQ-VAS instruments. Life expectancy and QALE at 40 years of age are calculated using the Sullivan-Chiang method and are stratified by educational attainment. Inequality is measured as the absolute and relative gap between individuals with lowest (i.e. primary school) and highest (university degree 4 + years) educational attainment. People with the highest educational attainment can expect to live longer lives (men: + 17.9% (95%CI: 16.4 to 19.5%), women: + 13.0% (95%CI: 10.6 to 15.5%)) and have higher QALE (men: + 22.4% (95%CI: 20.4 to 24.4%), women: + 18.3% (95%CI: 15.2 to 21.6%); measured using EQ-5D-5L) than individuals with primary school education. Relative inequality is larger when HRQoL is measured using EQ-VAS. Health inequalities by educational attainment become wider when measured in QALE rather than LE, and the degree of this widening is larger when measuring HRQoL by EQ-VAS than by EQ-5D-5L. We find a sizable educational gradient in lifetime health in Norway, one of the most developed and egalitarian societies in the world. Our estimates provide a benchmark against which other countries can be compared.


Parenteral nutrition. Pharmaceutical problems of compatibility and stability.
A typical All-in-One (AIO) parenteral nutrition mixture in a 3-litre polymeric infusion bag will consist of lipid emulsion, amino acids, glucose, electrolytes, trace elements and vitamins. This varied mixture of chemical entities provides the potential for a number of chemical and physicochemical interactions that can compromise the clinical safety and efficacy of the product. The destabilisation of the lipid emulsion in the presence of electrolytes is a major problem. Although a predictive equation for the maximum concentrations of mono-, di- and trivalent ions causing instability has been proposed, it is too simplistic to be of significant value. The reasons for this are discussed as well as the stability implications of other additives to the parenteral nutrition mixture.


Repurposing CD8+ T cell immunity against SARS-CoV-2 for cancer immunotherapy: a positive aspect of the COVID-19 pandemic?
The COVID-19 pandemic has afflicted most countries on the planet. As a result, immunity against SARS-CoV-2, induced via natural infections or imminent vaccinations, is expected to develop in a large fraction of the global population. Here, we propose to exploit SARS-CoV-2-specific CD8+ T cells for cancer immunotherapy strategies.


Regioselective Syntheses of Imidazo[4,5-b]pyrazin-2-ylidene-Based Chelates and Blue Emissive Iridium(III) Phosphors for Solution-Processed OLEDs.
Six homoleptic Ir(III) complexes bearing imidazo[4,5-b]pyrazin-2-ylidene chelates were successfully designed and synthesized. Narrowband blue emission (λmax = 466-485 nm) and broadened green emission (λmax = 518-532 nm) in degassed toluene solution with high photoluminescent quantum yields in the range of 75-81 and 45-48% were observed for f-timpz, t2impz, and t2empz as well as m-timpz, t2impz, and t2empz, respectively. In addition, the tert-butylphenyl cyclometalate is more electron donating than N-phenyl cyclometalate and, hence, all tert-butylphenyl-substituted derivatives, that is, m- and f-t2impz and m- and f-t2empz, give more red-shifted emission in comparison to that of m- and f-timpz. Moreover, solution-processed OLED with f-t2empz (20 wt %) as the dopant gave electrophosphorescence at 474 nm with maximum external quantum efficiency (max. EQE) of 5.1%, while hyper-OLED with assistant sensitizer f-t2empz (10 wt %) and the multi-resonance thermally activated delayed fluorescence emitter BCzBN (0.5 wt %) afforded narrowband emission centered at 485 nm and max. EQE up to 17.4%, confirming the high potential of this class of Ir(III) metal phosphors.


Roles of mPGES-1, an inducible prostaglandin E synthase, in enhancement of LPS-induced lymphangiogenesis in a mouse peritonitis model.
Lymphangiogenesis is frequently observed during inflammation, and this inflammation-induced lymphangiogenesis (IL) is a phenomenon actively involved in the pathophysiology of inflammation. We explored the roles of an inducible prostaglandin E synthase, mPGES-1, in IL elicited by lipopolysaccharide (LPS). Peritonitis was induced in mice by intraperitoneal injection of LPS (E. coli 0111-B4; 25μg/mouse every 2days), and IL was evaluated by LYVE-1 immunostaining of whole-mount diaphragm tissues. Compared to vehicle-treated wild-type (WT) mice, lymphatics in the diaphragms of mice injected with LPS were widened and the number of LYVE-1-positive ladder-structured lymphatics increased temporally. This increase in lymphangiogenesis was accompanied by increased expression of vascular endothelial growth factor (VEGF)-C/D in the diaphragms. In mice treated with celecoxib, a cyclooxygenase-2 inhibitor, IL was suppressed with reduced expression of VEGF-C/D. This was also observed in mPGES-1 knockout mice (KO). Immunoreactive COX-2 and mPGES-1 were detected in both CD11b-positive and CD3ε-positivecells in the diaphragm. When FITC-dextran was injected into the peritoneal cavities, the amount of residual FITC-dextran was reduced significantly in WT mice injected with LPS, and this reduction was significantly decreased in mPGES-1 KO mice. The present results suggest that mPGES-1 plays a significant role in lymphangiogenesis during inflammation, and represents a novel target for controlling IL.


Anisotropic and biomechanical properties of tendons modified by exercise and denervation: aggregation and macromolecular order in collagen bundles.
For the purpose of determining the changes in tensile strength and levels of macromolecular orientation in collagen bundles as a result of mechanical stimuli, rats were submitted to different experimental treatments such as physical exercise and muscular denervation. After these treatments the Achilles tendons of the animals were submitted to biomechanical and biophysical testing. An analysis of the "stress"-strain curves indicated that the tendons of trained animals possessed superior tensile strength characteristics as compared to their controls. The form birefringence curves (FBC) of the collagen bundles in these tendons also showed an increase in their state of aggregation of the extracellular matrix elements, while maintaining their levels of crystallinity. Average values of tensile strength were even higher in the tendons of denervated animals. An accentuation of the profile of the FBC was also observed in these tendons. The determination of the biomechanical and biophysical modifications can contribute to the understanding of the probable control mechanisms of the aggregation state patterns of the fibrous elements of the extracellular matrix.


Physical and chemical effects damaging listeriae (a short review).
This very brief summary attempts to review some of the more recent information on the physical and chemical conditions affecting survival and/or growth of listeriae in foods.


Immunotherapy and therapeutic vaccines for chronic HBV infection.
Chronic hepatitis B virus (HBV) infection is a major global health burden causing severe complications like liver cirrhosis or hepatocellular carcinoma. Curative treatment options are lacking. Therefore, there is an urgent need for new therapeutic options. Immunotherapy with the goal to restore dysfunctional HBV-specific T cell immunity is an interesting new therapeutic strategy. Based on current evidence on dysfunction of the HBV-specific CD8+ T cell response in chronic HBV infection, we will review the growing field of immunotherapeutic approaches for treatment of chronic HBV infection. The review will focus on therapies targeting T cells and will cover checkpoint inhibitors, T cell engineering, Toll-like receptor agonists and therapeutic vaccination.


Potential Risks for Healthcare Disparities Among Individuals With Voice and Upper Airway Disorders: A Systematic Review.
To assess the potential epidemiological association between various possible risk factors and healthcare disparities specifically related to the access, use and/or quality of speech language pathology services for individuals with voice and upper airway disorders. A systematic review was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis. Full text journal articles were identified through PubMed, PsycINFO and Web of Science. The reference sections of included articles were also manually screened and identified four additional studies for consideration of inclusion. Included articles specifically addressed healthcare disparities in voice and upper airway disorders related to speech pathology care. International literature was excluded. Eligible studies were reviewed and data extracted. Risk of bias of each eligible study was performed using the quality assessment tool from National Institute of Health for observational cohort and cross-sectional studies. Data from eligible studies were synthesized thematically. A total of 1,101 resources were retrieved from the search; of these, 133 were duplicates. Titles and abstracts of 968 articles were screened, with 14 selected for full-text review. Eleven articles were considered eligible for inclusion. Voice disorders were the condition most frequently examined followed by only one article addressing upper airways disorders. There was considerable heterogeneity in the methodology and statistical analyses among the eligible papers. There was a lack of standard methodology for collecting and accurately determining patient characteristics as well as variability in measuring confounding variables and providing statistical analyses for such adjustments that may have impacted the findings. The information extracted from these articles revealed healthcare disparities related to sex/gender, age, insurance status/coverage, race/ethnicity, among others including etiology and preferred language. This systematic review highlights the limited research on speech language pathology-specific healthcare disparities for individuals with voice and upper airway disorders. There was significant clinical and methodological heterogeneity between studies which may have contributed to varied results between studies. There is a need for greater methodological rigor and prospectively designed studies to better characterize the impact of disparities in the access to, use of, and quality of speech pathology care for this patient population.


Safety of cranial fixation in endoscopic brow lifts.
The endoscopic brow lift technique relies on brow mobilization and often soft fixation to the underlying calvarium. While the endoscopic brow lift has been used safely, there are anecdotal reports of cerebrospinal fluid leak. We sought to measure calvarial thickness to improve the safety of cranial fixation. A retrospective review was performed of T2 weighted MRIs of the face of 28 patients. Calvarial thickness was measured on 10 coronal planes, from 3 centimeters (cm) anterior to 6 cm posterior to coronal suture. Fifteen points were measured on each coronal plane, starting in the midline and extending laterally for 7 cm. There were a total of 150 calvarial measurements per patient, covering the surface area used in endoscopic brow lifts. Statistical comparison was performed using analysis of variance. Cranial thickness ranged from 1.1 to 13.6mm, with a mean of 6.1mm. The skull was thickest 2-4 cm posterior to the coronal suture, and thinnest 1cm anterior to the coronal suture. The cranium thins as it extends laterally, with an average thickness of 5.0mm at seven centimeters from midline. Average skull thickness for males was 5.96 versus 6.16 in females. There was no relationship between age and skull thickness. Cranial thickness increases medially and posteriorly, and is larger for females compared with their male counterparts. Given the risk of CSF leak, surgeons need to be aware of how cranial thickness varies by location along the skull.


Poor hygiene of housing conditions influences energy metabolism in a muscle type-dependent manner in growing pigs differing in feed efficiency.
The ability of pigs to cope with inflammatory challenges may by modified by selection for residual feed intake (RFI), a measure of feed efficiency. In the current study, we evaluated skeletal muscle metabolic responses to degraded hygiene conditions in pigs divergently selected for RFI. At 82 d of age, low RFI and high RFI pigs were housed in either poor or good hygiene conditions. After a 6-week challenge, the poor hygiene conditions induced a decrease in growth performance (P < 0.001) and in plasma IGF-I concentrations (P < 0.003) in both lines. In the slow-twitch oxidative semispinalis muscle, poor hygiene conditions induced a shift towards a more oxidative metabolism and an activation of the AMPK pathway in pigs of both RFI lines. In the fast-twitch glycolytic longississimus muscle, poor hygiene conditions were associated to a less glycolytic metabolism in the HRFI line only. Poor hygiene conditions also increased the protein level of lipidation of microtubule-associated protein 1 light-chain 3β (LC3-II) in both RFI lines, suggesting an activation of the autophagy pathway. Altogether, the data revealed muscle-type specific metabolic adaptations to poor hygiene conditions, which may be related to different strategies to fuel the activated immune system.


Ginsenoside Rh2 stimulates the production of mitochondrial reactive oxygen species and induces apoptosis of cervical cancer cells by inhibiting mitochondrial electron transfer chain complex.
Ginsenoside Rh2 (G‑Rh2) is a monomeric compound that extracted from ginseng and possesses anti‑cancer activities both in vitro and in vivo. Previously, we reported that G‑Rh2 induces apoptosis in HeLa cervical cancer cells and that the process was related to reactive oxygen species (ROS) accumulation and mitochondrial dysfunction. However, the upstream mechanisms of G‑Rh2, along with its cellular targets, remain to be elucidated. In the present study, the Cell Counting Kit‑8 assay, flow cytometry and Hoechst staining revealed that G‑Rh2 significantly inhibited cell viability and induced apoptosis of cervical cancer cells. However, G‑Rh2 was demonstrated to be non‑toxic to End1/e6e7 cells. JC‑1, rhodamine 123 staining, oxidative phosphorylation and glycolysis capacity assays demonstrated that G‑Rh2 exposure caused an immediate decrease in mitochondrial transmembrane potential due to its inhibition of mitochondrial oxidative phosphorylation, as well as glycolysis, both of which reduced cellular ATP production. Western blotting and electron transport chain (ETC) activity assays revealed that G‑Rh2 significantly inhibited the activity of ETC complexes I, III and V. Overexpression of ETC complex III partially significantly restored mitochondrial ROS and inhibited the apoptosis of cervical cancer cells induced by G‑Rh2. The predicted results of binding energy in molecular docking, confirmed that G‑Rh2 was highly likely to induce mitochondrial ROS production and promote cell apoptosis by targeting the ETC complex, especially for ETC complex III. Taken together, the present results revealed the potential anti‑cervical cancer activity of G‑Rh2 and provide direct evidence for the contribution of impaired ETC complex activity to cervical cancer cell death.


An anterograde tracer study on the development of corticospinal projections from the medial prefrontal cortex in the rat.
The aim of the present study is to investigate, both qualitatively and quantitatively, the development of corticospinal (CS) projections from the medial prefrontal cortex of the rat. This study was carried out with the use of anterogradely transported wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) after iontophoretic injections in the medial prefrontal cortex. For comparison similar injections are made in the sensorimotor cortex. The CS axons of neurons situated in the medial prefrontal cortex have reached the first thoracic segment (T1) at postnatal day 3 (P3) and reach their most caudal extension in the spinal cord sixth thoracic segment (T6) at postnatal day 7 (P7) and then gradually disappear during the second postnatal week. Quantitative results revealed that after labelling of the medial prefrontal cortex no peaks in labelling density, neither at the cervical nor at the lumbar intumescence, were present. Furthermore, the CS axons of medial prefrontal neurons never showed any outgrowth into the spinal grey matter at any age studied. Concludingly, the extension and subsequent elimination of CS axons originating in the medial prefrontal cortex follow a similar time course as those from the occipital cortex (Dev. Brain Res., 36 (1987) 121-130).


Hospitals and municipalities: working together to provide parking.
Partnerships between hospitals and local municipalities can solve the parking challenges of urban hospitals, according to the authors, who describe how one such partnership created effective and affordable parking that benefited both parties.


Influence of demographic and tumour variables on prostate cancer treatment with curative intent in Spain. Results of the 2010 national prostate cancer registry.
The aim of this study is to determine which cancer and demographic criteria influence the indication for surgery (radical prostatectomy) or radiation therapy (external or brachytherapy) in the treatment of prostate cancer. An analysis of the 2714 patients of the 2010 National Prostate Cancer Registry treated with curative intent. The analysed variables were age, prostate-specific antigen (PSA), prostate volume, the number of biopsy cores, the percentage of positive cores, the stage, Gleason score, the type of pathologist, the presence of perineural invasion and the study centre. We analysed the association among these variables and the type of treatment (surgery vs. radiation therapy/brachytherapy), using a univariate analysis (Student's t test and chi-squared) and a binary multiple logistic regression. The 48.12% of the patients (1306/2714) were treated with surgery, and 51.88% (1,408/2,714) underwent radiation therapy/brachytherapy. Differences were observed between the patients treated with prostatectomy and those treated with radiation therapy/brachytherapy (p<.05) in age (63.50±6.5 vs. 69.0±6.7), PSA (8.76±16.97 vs. 13.21±15.88), biopsied cores, percentage of positives cores (30.0±22 vs. 38.7±29), Gleason score (G6: 53.9% vs. 46.1%; G7: 45% vs. 55% G8-10: 26.6%, 73.4%), stage (localised: 50% vs. 50%; locally advanced: 14.6% vs. 85.4%), perineural invasion and hospital centre. In the multivariate analysis, the selected independent variables were age, PSA, percentage of positives cores, stage, Gleason score and hospital centre. According to our study, age, tumour aggressiveness and stage and the centre where the patient will be treated affect the selection of curative treatment for prostate cancer.


Assessing DNA Methylation in Cancer Stem Cells.
Many cancer-associated epigenetic signatures are also commonly observed in stem cells, just as epigenetic stem cell patterns are in cancer cells. DNA methylation is recognized as a hallmark of cancer development and progression. Herein, we describe two approaches to analyze DNA methylation, which can be applied to study or discover DNA methylation aberrations throughout the genome, as well as a more targeted investigation of regions of interest in cancer stem cells.


Preeclampsia in pregnancies with and without diabetes: the associations with placental weight. A population study of 655 842 pregnancies.
Women with diabetes are at increased risk of preeclampsia, and women with diabetes tend to deliver placentas and offspring that are large-for-gestational-age. We therefore studied placental weight in preeclamptic pregnancies according to maternal diabetes status. Information on all singleton births from 1999 through 2010 (n = 655 842) were obtained from the Medical Birth Registry of Norway. We used z-scores of placental weight to adjust for differences in gestational age at birth between deliveries, and compared the distribution of placental weight z-scores, in deciles, in preeclamptic pregnancies with and without diabetes, and in non-preeclamptic pregnancies with and without diabetes. Overall, the prevalence of preeclampsia was higher in pregnancies with diabetes than in pregnancies without diabetes (9.9% vs. 3.6%). Among preeclamptic pregnancies, having a placental weight in the highest decile was nearly three times more frequent (28.8%) in pregnancies with diabetes than in pregnancies without diabetes (9.8%). In the lowest decile, preeclamptic pregnancies with diabetes were underrepresented (7.5%), and preeclamptic pregnancies without diabetes were overrepresented (13.6%). Among pregnancies with preterm delivery, the above patterns were more pronounced, with 30.1% of the placentas in in preeclamptic pregnancies with diabetes in the highest decile, and 19.5% of the placentas in preeclamptic pregnancies without diabetes in the lowest decile. These results suggest that women with diabetes who develop preeclampsia have a higher placental weight than other women with preeclampsia or non-preeclamptic women.


Nocturnal enuresis at 7.5 years old: prevalence and analysis of clinical signs.
To determine the prevalence of nocturnal enuresis (NE) in a large cohort of children at 7.5 years old, and to examine the frequency of variables such as gender, severity, associated elimination problems, and clinical signs within the identified group. Of an original cohort of 13 971 infants alive at 12 months, 11 251 who were still active in the Avon Longitudinal Study of Parents and Children (ALSPAC) survey, were followed at 91 months. The mother or main carer was given a questionnaire which asked, amongst other items, about the presence and frequency of bedwetting, other elimination problems, and signs related to the wetting behaviour; 8269 (73.5%) questionnaires were returned and 8151 contained information on the frequency of bedwetting. In all, 1260 children (15.5%) at 7.5 years wet the bed, but most wet once or less a week, and only 215 (2.6%) met the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) criteria of NE (wetting at least twice a week). A higher prevalence was reported in boys than girls and 266 children (3.3%) had both daytime wetting and bedwetting, with 189 (2.3%) having both daytime soiling and bedwetting. Daytime urgency increased with severity of bedwetting and occurred in 28.9% of children with NE. At 7.5 years old the incidence of bedwetting is high, but only 2.6% of this large population-based sample wet at a frequency meeting the definition of NE. Although a small percentage of children had both daytime wetting and bedwetting, the evidence suggests that these are discrete problems. Amongst children with NE, indicators of bladder overactivity were present, supporting the view of heterogeneity and the importance of individual assessment in deciding on appropriate treatment.


Fetal growth trajectories of small/large for gestational age infants in twin pregnancies.
Birthweight is the most common and accessible parameter in assessing neonatal perinatal outcomes and in evaluating the intrauterine environment globally. Infants born too large or too small not only may alter the maternal mode of delivery but also may face other long-term disorders, such as metabolic diseases and neurodevelopmental delay. Studies have revealed different growth profiles of large-for-gestational-age and small-for-gestational-age fetuses in singleton pregnancies. However, currently, no research is focused on the growth trajectories of these infants during twin pregnancies, even though they are at a much higher risk of being small for gestational age. This study aimed to explore fetal growth trajectories of large-for-gestational-age and small-for-gestational-age infants in twin pregnancies to provide strategies for fetal growth management. This was a case-control study of all noncomplicated twin pregnancies delivered after 36 weeks of gestation at the Peking University First Hospital between 2012 and 2021. Ultrasound data were recorded every 2 to 4 weeks until delivery. All the infants were divided into large-for-gestational-age, small-for-gestational-age, and appropriate-for-gestational-age groups. Longitudinal fetal growth (estimated fetal weight, abdominal circumference, etc.) was compared among the 3 groups using a linear mixed model, and other maternal and neonatal perinatal outcomes were compared. Receiver operating characteristic curves were used to explore optimal biometric parameters and gestational weeks for predicting small-for-gestational-age infants. Here, 797 pregnant patients with 1494 infants were recruited, with 59 small-for-gestational-age infants, 1335 appropriate-for-gestational-age infants, and 200 large-for-gestational-age infants. The mean birthweights were 1985.34±28.34 g in small-for-gestational-age infants, 2662.08±6.60 g in appropriate-for-gestational-age infants, and 3231.24±11.04 g in large-for-gestational-age infants. The estimated fetal weight of the 3 groups differed from each other from week 26, with the small-for-gestational-age fetuses weighing 51.946 g less and the large-for-gestational-age fetuses weighing 35.233 g more than the appropriate-for-gestational-age fetuses. This difference increased with gestation; at 39 weeks, the small-for-gestational-age fetuses weighed 707.438 g less and the large-for-gestational-age fetuses weighed 614.182 g more than the appropriate-for-gestational-age fetuses (all P<.05). The small-for-gestational-age group had a significantly higher rate of hospitalization (89.9 %) and jaundice (40.7 %) than the appropriate-for-gestational-age group, whereas the hospitalization rate in the large-for-gestational-age group was significantly lower than the appropriate-for-gestational-age group (7.5% and 2.5%; all P<.05). The fetal weight of the small-for-gestational-age infants with adverse outcomes remained near the 10th percentile of the reference and fell below the 3rd percentile at 34 weeks of gestation. The estimated fetal weight after 30 weeks of gestation had a satisfactory diagnostic value in predicting small-for-gestational-age infants. At 30, 32, 34, and 36 weeks of gestation, the areas under the curve were 0.829, 0.840, 0.929, and 0.889 respectively. The growth patterns of small-for-gestational-age, appropriate-for-gestational-age, and large-for-gestational-age twin fetuses diverged from 26 weeks of gestation and continued to increase until delivery; therefore, closer monitoring is suggested from 26 weeks of gestation for those carrying small fetuses.


Effects of Astragalus polysaccharides on intestinal morphology and intestinal immune cells of Muscovy ducklings infected with Muscovy duck reovirus.
Muscovy duck reovirus (MDRV) infection induces serious immunosuppression and intestinal injury in Muscovy ducklings with a high morbidity and mortality, and Astragalus polysaccharide (APS) pretreatment could efficiently protect ducklings from MDRV infection, although the underlying immunoregulatory mechanisms remain unclear. Thus, the objective of this study was to investigate effects of APS on the intestinal mucosal immunity in MDRV-infected Muscovy ducklings. A total of 190 1-day-old healthy Muscovy ducklings were randomly assigned to 3 groups (n = 50): normal control group, APS pretreatment for MDRV-infected group, and cohabitation infection group, then pretreated with 0.6 g/L APS or only drinking water followed by MDRV cohabitation infection with the remaining 40 artificially infected ducklings, respectively. At the 2, 3, 4, 6, 9 and 15 d after cohabitation infection, the intestinal samples were prepared to measure intestinal parameters including villus length, villus length/crypt depth (V/C) ratio, and wall thickness, together with counts of intraepithelial lymphocyte (IEL) and goblet cell (GC) by hematoxylin-eosin staining. Meanwhile, ileal secretory IgA (sIgA) and duodenal cytokine levels of IL-4, IL-6, IL-15, tumor necrosis factor-alpha, and interferon gamma were detected by the ELISA and radioimmunoassay, respectively. The results showed that APS significantly improved intestinal injuries of villi length, V/C ratio, and wall thickness of the small intestine infected with MDRV, effectively inhibited the reduction of IEL and GC caused by MDRV infection, subsequently increased sIgA and all the cytokine secretions at most time points, suggesting that APS pretreatment can effectively stimulate mucosal immune function by improving intestinal morphology and repair MDRV caused injures of small intestinal mucosal immune barrier in infected ducklings. Our findings lay the foundation for further application of APS in prevention and treatment of MDRV infection.


Exploration of Malignant Characteristics in Neoadjuvant Chemotherapy-Resistant Rectal Cancer, Focusing on Extramural Lesions.
Extramural vascular invasion (EMVI) and tumor deposits (TD) are poor prognostic factors in rectal cancer (RC), especially when resistant to neoadjuvant chemotherapy (NAC). We aimed to define differential expression in NAC responders and non-responders with concomitant EMVI and TD. From 52 RC surgical patients, post-NAC resected specimens were extracted, comprising two groups: cases with residual EMVI and TD (NAC-resistant) and cases without (NAC-effective). Proteomic analysis was conducted to define differential protein expression in the two groups. To validate the findings, immunohistochemistry was performed in another cohort that included 58 RC surgical patients. Based on the findings, chemosensitivity and prognosis were compared. The NAC-resistant group was associated with a lower 3-year disease-free survival rate than the NAC-effective group (p = 0.041). Discriminative proteins in the NAC-resistant group were highly associated with the sulfur metabolism pathway. Among these pathway constituents, selenium-binding protein 1 (SELENBP1) expression in the NAC-resistant group decreased to less than one-third of that of the NAC-effective group. Immunohistochemistry in another RC cohort consistently validated the relationship between decreased SELENBP1 and poorer NAC sensitivity, in both pre-NAC biopsy and post-NAC surgery specimens. Furthermore, decrease in SELENBP1 was associated with a lower 3-year disease-free survival rate (p = 0.047). We defined one of the differentially expressed proteins in NAC responders and non-responders, concomitant with EMVI and TD. SELENBP1 was suspected to contribute to NAC resistance and poor prognosis in RC.


Project-based Housing First for chronically homeless individuals with alcohol problems: within-subjects analyses of 2-year alcohol trajectories.
Two-year alcohol use trajectories were documented among residents in a project-based Housing First program. Project-based Housing First provides immediate, low-barrier, nonabstinence-based, permanent supportive housing to chronically homeless individuals within a single housing project. The study aim was to address concerns that nonabstinence-based housing may enable alcohol use. A 2-year, within-subjects analysis was conducted among 95 chronically homeless individuals with alcohol problems who were allocated to project-based Housing First. Alcohol variables were assessed through self-report. Data on intervention exposure were extracted from agency records. Multilevel growth models indicated significant within-subjects decreases across alcohol use outcomes over the study period. Intervention exposure, represented by months spent in housing, consistently predicted additional decreases in alcohol use outcomes. Findings did not support the enabling hypothesis. Although the project-based Housing First program did not require abstinence or treatment attendance, participants decreased their alcohol use and alcohol-related problems as a function of time and intervention exposure.


Development of Rice-Seed-Based Oral Allergy Vaccines Containing Hypoallergenic Japanese Cedar Pollen Allergen Derivatives for Immunotherapy.
Allergen-specific immunotherapy is the only available curative treatment for IgE-mediated allergen diseases. A safe hypoallergenic allergen derivative with high efficiency is required as a tolerogen to induce immune tolerance to the causitive allergens. In this study, to generate a rice-based oral allergy vaccine for Japanese cedar (JC) pollinosis, the tertiary structures of major JC pollen allergens, Cry j 1 and Cry j 2, were more completely destructed by shuffling than the previous ones without losing immunogenicity and then were specifically expressed in the endosperm of transgenic rice seed. They accumulated at high levels and were deposited in endoplasmic reticulum (ER) and ER-derived protein bodies. The low allergenicity of these deconstructed Cry j 1 and Cry j 2 allergens was evaluated by examining their binding activities to the specific IgE antibody and by the basophil degranulation test.


Lactosylceramide-enriched microdomains mediate human neutrophil immunological functions via carbohydrate-carbohydrate interaction.
The innate immune system of mammalian cells is the first line of defense against pathogenic microorganisms. Phagocytes, which play the central role in this system, engulf microorganisms by a mechanism that involves pattern recognition receptors on their own surface and pathogen-associated molecular patterns (PAMPs) expressed by the microorganism. Components of PAMPs include glycans (polysaccharides) and glycoconjugates (carbohydrates covalently linked to other biological molecules). Pathogenic microorganisms display specific binding affinity to various types of glycosphingolipids (sphingosine-containing glycolipids; GSLs), and GSLs are involved in host-pathogen interactions. We observed that lactosylceramide (LacCer), a neutral GSL, binds directly to certain pathogen-specific molecules (e.g., Candida albicans-derived β-glucans, mycobacterial lipoarabinomannan) via carbohydrate-carbohydrate interaction. LacCer is expressed highly on human neutrophils, and forms membrane microdomains. Such LacCer-enriched microdomains mediate several important neutrophil functions, including chemotaxis, phagocytosis, and superoxide generation. Human neutrophils phagocytose pathogenic mycobacteria (including Mycobacterium tuberculosis) through carbohydrate-carbohydrate interaction between LacCer on their own surface and mannose-capped lipoarabinomannan on the bacterium. During recognition of pathogen-specific glycans, direct association of LacCer-containing C24 fatty acid chain with Lyn (a Src family kinase) is necessary for signal transduction from the neutrophil exterior to interior. Pathogenic mycobacteria utilize a similar interaction to avoid killing by neutrophils. We describe here the mechanisms whereby LacCer mediates neutrophil immune systems via carbohydrate-carbohydrate interaction.


Does witness type affect the chance of receiving bystander CPR in out-of-hospital cardiac arrest?
The relationship between the bystander witness type and receipt of bystander CPR (BCPR) is not well understood. Herein we compared BCPR administration between family and non-family witnessed out-of-hospital cardiac arrest (OHCA). In many communities, interventions in the past decade have contributed to an increased receipt of BCPR, for example in Singapore from 15% to 60%. However, BCPR rates have plateaued despite sustained and ongoing community-based interventions, which may be related to gaps in education or training for various witness types. The purpose of this study was to investigate the association between witness type and BCPR administration. Singapore data from 2010-2020 was extracted from the Pan-Asian Resuscitation Outcomes Study (PAROS) network registry (n = 25,024). All adult, layperson witnessed, non-traumatic OHCAs were included in this study. Of 10,016 eligible OHCA cases, 6,895 were family witnessed and 3,121 were non-family witnessed. After adjustment for potential confounders, BCPR administration was less likely for non-family witnessed OHCA (OR 0.83, 95% CI 0.75, 0.93). After location stratification, non-family witnessed OHCAs were less likely to receive BCPR in residential settings (OR 0.75, 95% CI 0.66, 0.85). In non-residential settings, there was no statistically significant association between witness type and BCPR administration (OR 1.11, 95% CI 0.88, 1.39). Details regarding witness type and bystander CPR were limited. This study found differences in BCPR administration between family and non-family witnessed OHCA cases. Elucidation of witness characteristics may be useful to determine populations that would benefit most from CPR education and training.


The sense of coherence, occupation and all-cause mortality in the Helsinki Heart Study.
The aim of this study was to test the hypothesis that people with a strong sense of coherence (SOC) have decreased all-cause mortality. The effect of occupation and the SOC on all-cause mortality was studied among 4405 Finnish middle-aged employed men in a prospective 8-year follow-up study. Using Cox proportional hazards models the crude relative risk for all-cause mortality for the low SOC tertile when compared to the high SOC tertile was 1.23 (95% CI: 0.90-1.68). Adjusting for age, smoking, alcohol and occupation increased the risk slightly to 1.35. Occupation was an effect modifier, since among white-collar workers the corresponding relative risk of the low SOC tertile was 2.27 (95% CI: 1.12-4.59, p = 0.02) and among blue-collar workers the relative risk for all-cause mortality was stable (1.33-1.52) in each SOC tertile. The classic risk factors, smoking and alcohol, showed higher relative risks than the SOC. The effect of the health-promoting qualities of the SOC upon all-cause mortality was significant among white-collar workers, but not among blue-collar workers.


Z Score Reference Ranges of Fetal Cardiothoracic Diameter Ratio.
This study aims to establish the z score reference ranges of cardiothoracic diameter ratio (CTR) of normal fetuses from 14 to 40 weeks' gestation. A cross-sectional study was conducted on low-risk singleton pregnancies with healthy fetuses. The CTR was performed using simple 2-dimensional sonography on the typical fetal 4-chamber view. The reference ranges were constructed according to gestational age (GA), biparietal diameter (BPD), and head circumference (HC) as independent variables based on the best-fit models, both mean and standard deviation (SD). A total of 683 fetuses were measured for CTR. The best-fit equations for the mean and SD as a function of GA, BPD, and HC are as follows: (1) CTR = 0.365 + 0.004 × GA in weeks (SD = 0.031 + 0.001 × GA); (2) CTR = 0.373 + 0.014 × BPD in cm (SD = 0.034 + 0.004 × BPD); and (3) CTR = 0.373 + 0.004 × HC in cm (SD = 0.032 + 0.001 × HC). The CTR was slightly increased with advanced GA, BPD, and HC. Complete nomograms with z score reference ranges of CTR were established throughout pregnancy. These nomograms may be useful to detect cardiac abnormalities.


Factors that influence the incision-delivery interval at caesarean section and the impact on the neonate: a prospective cohort study.
To determine the range of, and influences on, the incision-delivery interval (IDI) and the impact on neonatal condition at delivery. Analysis of prospectively collected cohort data from all women delivered by caesarean section over 12 months in an obstetric unit delivering 6000 women per year. Prospective data were collected from clinical records, with factors that influence IDI and relationship to neonatal condition at birth as the main outcome measures. IDI was recorded for 1379 (93%) caesarean sections and ranged between 1 and 37min; median (IQR) was 6 (5-8)min, and for 3% the interval was longer than 15min. Category 1 and 2 caesarean sections had shorter IDI than categories 3 and 4 and intrapartum operations had significantly shorter IDI at 5 (3-8)min than antepartum at 7 (5-9)min (P<0.0001). Factors associated with longer IDI included previous delivery by caesarean section, increased maternal body mass index (BMI), regional anaesthesia, larger neonatal birthweight and technical problems including intraperitoneal adhesions, but did not include fetal malpresentation, multiple pregnancy, grade of surgeon or stage of labour. IDI had no impact on neonatal condition at birth. Prolonged IDI does not adversely affect neonatal outcome, but factors associated with prolonged IDI should be acknowledged when assessing decision-to-delivery interval target times.


Cytokines in skin lesions of psoriasis.
Cytokine levels were compared in aqueous extracts of stratum corneum from psoriatic lesions and normal heel. Samples from heel contained high levels of interleukin-1 alpha (IL-1 alpha) and beta measured in immunoassays, although only the IL-1 alpha was biologically active. No other cytokines could be detected in heel samples. Interleukin-1 (IL-1) levels were dramatically reduced in lesional samples. A neutrophil chemoattractant was found in all lesional extracts, and was demonstrated to be mainly interleukin-8 (IL-8) using a specific neutralizing antiserum. Tumor necrosis factor alpha (TNF-alpha) and beta (TNF-beta), and interferon alpha (IFN-alpha) and gamma (IFN-gamma) were detected in lesional extracts using immunoassays, however, no equivalent biological activities could be detected. Interleukins 2 (IL-2), 4 (IL-4), and 6 (IL-6), granulocyte and granulocyte/macrophage colony stimulating factor (GM-CSF), could not be detected in any samples. IL-8 is therefore the only biologically active cytokine shown in this study to be elevated in psoriatic lesional extracts, and may therefore play a role in the pathogenesis of the disease.


Identification of new molecules extracted from Quercus suber L. cork.
Various methods of suberin extraction have been used in order to identify monomers of this complex polymer. Pre-extraction of waxes has allowed us to identify for the first time 3-friedelanol as a terpen from cork. Moreover, the wax chemical composition found here varied from previous results since cerin was not identified while friedelin and betulin were. Three fractions were obtained: a polymeric, a monomeric and a low molecular weight fraction, the last of which has never before been described. 2,6-heptanediol was found to be the main compound of this fraction. Furthermore, depolymerisation at room temperature gives the same yields as those obtained at reflux, defining an easier and cheaper methodology.


Sensitized photo-oxidation of gadusol species mediated by singlet oxygen.
Gadusols are efficient nature UV sunscreens with antioxidant capacity. The kinetics of the quenching reactions of singlet oxygen O2(1∆g) by gadusol species was evaluated in aqueous solution as well as in the presence of direct charged micelles. Time-resolved phosphorescence detection of O2(1∆g) indicated that gadusolate, the main species under biological pH, is a more efficient quencher than the enol form with a rate constant of ca. 1.3 × 108 L mol-1 s-1. The deactivation proceeds via a collisional mechanism with clear dominance of chemical pathways, according to the rates of gadusol and oxygen consumptions, and typical photooxidation quantum yields of ca. 7%. The relative contributions of the chemical and physical quenching steps were not affected by the presence of anionic or cationic micelles emulating simple pseudo-biological environments. The products of the photo-oxidative quenching support a type II mechanism initiated by the addition of O2(1∆g) to the C-C double bond of gadusolate. These results point to the relevance of considering the role of sacrifice antioxidant along with the UV-screening function for gadusol, particularly in the context of potential biotechnological applications of this natural molecule.


Why do fleshy-fruit plants of the mediterranean scrub intercept fall-but not spring-passage of seed-dispersing migratory birds?
Production of fleshy fruits by 8 tree and shrub species, and patterns of their utilization by 6 resident and 6 transient bird species, were assessed in an Israeli Mediterranean scrub. Whereas more than half the ripe crop of plants that fruit in one relatively short burst is not removed by birds, the greater part of the crop of species that fruit throughout a long period, is removed. Of two plant species that fruit simultaneously, the one with an inconspicuous fruit is utilized by a single, year-round resident frugivorous bird, whereas the species with bright fruits is utilized by several non-resident and omnivorous bird species. A further two simultaneously fruiting species differ in fat content and the color of their conspicuous ripe fruits; the low-fat fruit being taken by a resident species and the high-fat fruit by a transient congener, just prior to the desert-crossing portion of its Fall-passage.Though more migrants pass through in Spring than in Fall, none of the fleshy-fruit plants fruit in Spring, and most fruit during the Fall. Two non-exclusive explanations for this phenomenon are (a) Fall dispersal ensures immediate germination, with least exposure to desiccation and predation; (b) Spring transients approaching their breeding territories may either be reluctant to spend much time on feeding, or mostly require proteins, amply supplied by the Spring flush of insects, typical of the Mediterranean region. Fall transients approaching the desert require mostly fats and carbohydrates, supplied by fruits. Fruits attract birds easily in the Fall, when insects are scarce.


Does fingolimod in multiple sclerosis patients cause macular edema?
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system and is the common cause of optic neuritis. Fingolimod, an immunosuppressive agent, is used in MS to prevent acute exacerbations. We report a case of relapsing-remitting MS treated with fingolimod. The patient presented with an acute decrease in vision in the left eye. Eye examination showed clinical macular edema (ME) in the left eye, which was confirmed on fluorescein angiogram and optical coherence tomography (OCT). After discontinuation of fingolimod and treatment with topical corticosteroid medication, there was complete resolution of the ME. The ME as a side-effect of fingolimod is reversible after discontinuing, which was seen on OCT.