Mechanisms of oligodendrocyte regeneration from ventricular-subventricular zone-derived progenitor cells in white matter diseases.
White matter dysfunction is an important part of many CNS disorders including multiple sclerosis (MS) and vascular dementia. Within injured areas, myelin loss and oligodendrocyte death may trigger endogenous attempts at regeneration. However, during disease progression, remyelination failure may eventually occur due to impaired survival/proliferation, migration/recruitment, and differentiation of oligodendrocyte precursor cells (OPCs). The ventricular-subventricular zone (V-SVZ) and the subgranular zone (SGZ) are the main sources of neural stem/progenitor cells (NSPCs), which can give rise to neurons as well as OPCs. Under normal conditions in the adult brain, the V-SVZ progenitors generate a large number of neurons with a small number of oligodendrocyte lineage cells. However, after demyelination, the fate of V-SVZ-derived progenitor cells shifts from neurons to OPCs, and these newly generated OPCs migrate to the demyelinating lesions to ease white matter damage. In this mini-review, we will summarize the recent studies on extrinsic (e.g., vasculature, extracellular matrix (ECM), cerebrospinal fluid (CSF)) and intrinsic (e.g., transcription factors, epigenetic modifiers) factors, which mediate oligodendrocyte generation from the V-SVZ progenitor cells. A deeper understanding of the mechanisms that regulate the fate of V-SVZ progenitor cells may lead to new therapeutic approaches for ameliorating white matter dysfunction and damage in CNS disorders.


TRPV1 activation stimulates NKCC1 and increases hydrostatic pressure in the mouse lens.
The porcine lens response to a hyperosmotic stimulus involves an increase in the activity of an ion cotransporter sodium-potassium/two-chloride cotransporter 1 (NKCC1). Recent studies with agonists and antagonists pointed to a mechanism that appears to depend on activation of transient receptor potential vanilloid 1 (TRPV1) ion channels. Here, we compare responses in lenses and cultured lens epithelium obtained from TRPV1-/- and wild type (WT) mice. Hydrostatic pressure (HP) in lens surface cells was determined using a manometer-coupled microelectrode approach. The TRPV1 agonist capsaicin (100 nM) caused a transient HP increase in WT lenses that peaked after ∼30 min and then returned toward baseline. Capsaicin did not cause a detectable change of HP in TRPV1-/- lenses. The NKCC inhibitor bumetanide prevented the HP response to capsaicin in WT lenses. Potassium transport was examined by measuring Rb+ uptake. Capsaicin increased Rb+ uptake in cultured WT lens epithelial cells but not in TRPV1-/- cells. Bumetanide, A889425, and the Akt inhibitor Akti prevented the Rb+ uptake response to capsaicin. The bumetanide-sensitive (NKCC-dependent) component of Rb+ uptake more than doubled in response to capsaicin. Capsaicin also elicited rapid (<2 min) NKCC1 phosphorylation in WT but not TRPV1-/- cells. HP recovery was shown to be absent in TRPV1-/- lenses exposed to hyperosmotic solution. Bumetanide and Akti prevented HP recovery in WT lenses exposed to hyperosmotic solution. Taken together, responses to capsaicin and hyperosmotic solution point to a functional role for TRPV1 channels in mouse lens. Lack of NKCC1 phosphorylation and Rb+ uptake responses in TRPV1-/- mouse epithelium reinforces the notion that a hyperosmotic challenge causes TRPV1-dependent NKCC1 activation. The results are consistent with a role for the TRPV1-activated signaling pathway leading to NKCC1 stimulation in lens osmotic homeostasis.


Cost and effectiveness of one session treatment (OST) for children and young people with specific phobias compared to multi-session cognitive behavioural therapy (CBT): results from a randomised controlled trial.
In the UK, around 93,000 (0.8%) children and young people (CYP) are experiencing specific phobias that have a substantial impact on daily life. The current gold-standard treatment-multi-session cognitive behavioural therapy (CBT) - is effective at reducing specific phobia severity; however, CBT is time consuming, requires specialist CBT therapists, and is often at great cost and limited availability. A briefer variant of CBT called one session treatment (OST) has been found to offer similar clinical effectiveness for specific phobia as multi-session CBT. The aim of this study was to assess the cost-effectiveness of OST compared to multi-session CBT for CYP with specific phobias through the Alleviating Specific Phobias Experienced by Children Trial (ASPECT), a two-arm, pragmatic, multi-centre, non-inferiority randomised controlled trial. CYP aged seven to 16 years with specific phobias were recruited nationally via Health and Social Care pathways, remotely randomised to the intervention group (OST) or the control group (CBT-based therapies) and analysed (n = 267). Resource use based on NHS and personal social services perspective and quality adjusted life years (QALYs) measured by EQ-5D-Y were collected at baseline and at six-month follow-up. Incremental cost-effectiveness ratio (ICER) was calculated, and non-parametric bootstrapping was conducted to capture the uncertainty around the ICER estimates. The results were presented on a cost-effectiveness acceptability curve (CEAC). A set of sensitivity analyses (including taking a societal perspective) were conducted to assess the robustness of the primary findings. After adjustment and bootstrapping, on average CYP in the OST group incurred less costs (incremental cost was -£302.96 (95% CI -£598.86 to -£28.61)) and maintained similar improvement in QALYs (QALYs gained 0.002 (95% CI - 0.004 to 0.008)). The CEAC shows that the probability of OST being cost-effective was over 95% across all the WTP thresholds. Results of a set of sensitivity analyses were consistent with the primary outcomes. Compared to CBT, OST produced a reduction in costs and maintained similar improvement in QALYs. Results from both primary and sensitivity analyses suggested that OST was highly likely to be cost saving. ISRCTN19883421 (30/11/2016).


Key features of wave energy.
For a weak point source or dipole, or a small body operating as either, we show that the power from a wave energy converter (WEC) is the product of the particle velocity in the waves, and the wave force (suitably defined). There is a thus a strong analogy with a wind or tidal turbine, where the power is the product of the fluid velocity through the turbine, and the force on it. As a first approximation, the cost of a structure is controlled by the force it has to carry, which governs its strength, and the distance it has to be carried, which governs its size. Thus, WECs are at a disadvantage compared with wind and tidal turbines because the fluid velocities are lower, and hence the forces are higher. On the other hand, the distances involved are lower. As with turbines, the implication is also that a WEC must make the most of its force-carrying ability-ideally, to carry its maximum force all the time, the '100% sweating WEC'. It must be able to limit the wave force on it in larger waves, ultimately becoming near-transparent to them in the survival condition-just like a turbine in extreme conditions, which can stop and feather its blades. A turbine of any force rating can achieve its maximum force in low wind speeds, if its diameter is sufficiently large. This is not possible with a simple monopole or dipole WEC, however, because of the 'nλ/2π' capture width limits. To achieve reasonable 'sweating' in typical wave climates, the force is limited to about 1 MN for a monopole device, or 2 MN for a dipole. The conclusion is that the future of wave energy is in devices that are not simple monopoles or dipoles, but multi-body devices or other shapes equivalent to arrays.


Neurotransmitter function in the basal ganglia after acute and chronic ethanol treatment.
Acute and chronic administration of ethanol has multiple effects on several neurotransmitters in the basal ganglia. Dopamine is the transmitter predominantly affected. Acceleration of dopaminergic activity is observed at low doses of ethanol. However, at high doses the reverse is observed. During the ethanol withdrawal syndrome that develops after chronic treatment, dopaminergic responses are reduced, whether from presynaptic or postsynaptic origins. Evidence also indicates that cholinergic and GABAergic processes may be implicated in these actions of ethanol. Ethanol apparently induces a variety of alterations in neurotransmitter function as a result of its disruption of membrane structure and associated electric properties.


Global prevalence and content of information about alcohol use as a cancer risk factor on Twitter.
Alcohol use is a major risk factor for several forms of cancer, though many people have limited knowledge of this link. Public health communicators and cancer advocates desire to increase awareness of this link with the long-term goal of reducing cancer burden. The current study is the first to examine the prevalence and content of information about alcohol use as a cancer risk on social media internationally. We used a three-phase process (hashtag search, dictionary-based auto-identification of content, and human coding of content) to identify and evaluate information from Twitter posts between January 2019 and December 2021. Our hashtag search retrieved a large set of cancer-related tweets (N = 1,122,397). The automatic search process using an alcohol dictionary identified a small number of messages about cancer that also mentioned alcohol (n = 9061, 0.8%), a number that got small after adjusting for human coded estimates of the dictionary precision (n = 5927, 0.5%). When cancer-related messages also mentioned alcohol, 82% (n = 1003 of 1225 examined through human coding) indicated alcohol use as a risk factor. Coding found rare instances of problematic information (e.g., promotion of alcohol, misinformation) in messages about alcohol use and cancer. Few social media messages about cancer types that can be linked to alcohol mention alcohol as a cancer risk factor. If public health communicators and cancer advocates want to increase knowledge and understanding of alcohol use as a cancer risk factor, efforts will need to be made on social media and through other communication platforms to increase exposure to this information over time.


[The findings and sequence of events leading to termination of pregnancy due to Down's syndrome--before and after the verge of viability: 10 years experience at a single medical center].
To assess the differences in the sequence of events, leading to termination of pregnancy (TOP) due to diagnosis of Down syndrome (DS). The study compared women who were referred to institutional abortion committees (< 23 weeks) to those who were referred to supreme regional abortion committees (> 23 weeks). Cases of singleton pregnancy ending in TOP due to DS in our institute during the period January 2000-December 2010 were retrospectively reviewed. The women were divided into two groups according to the gestational age at the time of the TOP. Group 1 included women who underwent TOP prior to 23 weeks of pregnancy; group 2 included women who had TOP at 23 weeks and onwards. The groups were compared regarding their demographic, sonographic and biochemical parameters during the affected pregnancy. Women in group 2 completed a telephone questionnaire about the circumstances leading to a late TOP after 23 weeks. There were 303 cases of DS, which had TOP during this period of time. All cases were diagnosed by fetal karyotyping. A total of 282 cases (93%) had earlier TOP while 21 cases (7%) had late TOP. The mean gestational age in each group was 18 weeks (range 12-22 weeks] versus 24 weeks (18-34 weeks) respectively (p < 0.001). In group 2, there were significantly more abnormal cardiovascular findings (67% vs. 21% in group 1, p < 0.002). No other significant differences were found between the groups regarding the demographic parameters, biochemical screening results (triple test), nuchal translucency (NT) and early and/or late sonographic anomaly scans. In Group 2 a total of 9 (42.8%) out of 21 women agreed to answer the telephone questionnaire. In this group the triple test, was performed in the upper recommended time limit according to the Ministry of Health. This may have led to the delay in the TOP. In our institutional experience we found that the circumstances leading to late TOPs because of DS were maternal dependent and not related to the screening findings. This stresses the efficiency of current screening programs, leading to early karyotyping and diagnosis of DS.


Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group.
To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection. A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids. At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment. The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.


Tissue effects resulting from eraser laser enucleation of the prostate: in vivo investigation.
BACKGROUND/AIMS/OBJECTIVES: To describe the depth of the laser coagulation zone in vivo based on histological examinations and the functional outcome of a 1,318-nm diode laser for enucleation in benign prostatic enlargement (BPE). A total of 20 patients with BPE were treated by laser Eraser® enucleation of the prostate (ELEP). Prostatic tissue wedges were evaluated to assess the depth of the ELEP coagulation zones. Additionally, patients were assessed preoperatively and 12 months postoperatively. The coagulation zones were 0.36 ± 0.17 mm in epithelial tissue, 0.28 ± 0.15 mm in stromal tissue, and 0.25 ± 0.12 mm in mixed tissue. The coagulation area at the cutting edge completely sealed capillary vessels, reaching a depth of 0.35 ± 0.15 mm. The diameter of the coagulated vessels measured 1.75 ± 0.83 mm. Mean blood loss was 115.54 ± 93.12 ml, catheter time 1.35 ± 0.33 days, and hospital stay 1.89 ± 0.52 days. The International Prostate Symptom Score, maximal flow rate, and quality of life significantly improved 12 months after the procedure. ELEP is safe and effective for BPE treatment and yields good results at a follow-up of 1 year. Because of the limited penetration depth, damage to the urinary sphincter is not expected.


Individual-based ecology of coastal birds.
Conservation objectives for non-breeding coastal birds (shorebirds and wildfowl) are determined from their population size at coastal sites. To advise coastal managers, models must predict quantitatively the effects of environmental change on population size or the demographic rates (mortality and reproduction) that determine it. As habitat association models and depletion models are not able to do this, we developed an approach that has produced such predictions thereby enabling policy makers to make evidence-based decisions. Our conceptual framework is individual-based ecology, in which populations are viewed as having properties (e.g. size) that arise from the traits (e.g. behaviour, physiology) and interactions of their constituent individuals. The link between individuals and populations is made through individual-based models (IBMs) that follow the fitness-maximising decisions of individuals and predict population-level consequences (e.g. mortality rate) from the fates of these individuals. Our first IBM was for oystercatchers Haematopus ostralegus and accurately predicted their density-dependent mortality. Subsequently, IBMs were developed for several shorebird and wildfowl species at several European sites, and were shown to predict accurately overwinter mortality, and the foraging behaviour from which predictions are derived. They have been used to predict the effect on survival in coastal birds of sea level rise, habitat loss, wind farm development, shellfishing and human disturbance. This review emphasises the wider applicability of the approach, and identifies other systems to which it could be applied. We view the IBM approach as a very useful contribution to the general problem of how to advance ecology to the point where we can routinely make meaningful predictions of how populations respond to environmental change.


Self-assembled nanocomplex between polymerized phenylboronic acid and doxorubicin for efficient tumor-targeted chemotherapy.
Since the discovery that nano-scaled particulates can easily be incorporated into tumors via the enhanced permeability and retention (EPR) effect, such nanostructures have been exploited as therapeutic small molecule delivery systems. However, the convoluted synthetic process of conventional nanostructures has impeded their feasibility and reproducibility in clinical applications. Herein, we report an easily prepared formulation of self-assembled nanostructures for systemic delivery of the anti-cancer drug doxorubicin (DOX). Phenylboronic acid (PBA) was grafted onto the polymeric backbone of poly(maleic anhydride). pPBA-DOX nanocomplexes were prepared by simple mixing, on the basis of the strong interaction between the 1,3-diol of DOX and the PBA moiety on pPBA. Three nanocomplexes (1, 2, 4) were designed on the basis of [PBA]:[DOX] molar ratios of 1:1, 2:1, and 4:1, respectively, to investigate the function of the residual PBA moiety as a targeting ligand. An acid-labile drug release profile was observed, owing to the intrinsic properties of the phenylboronic ester. Moreover, the tumor-targeting ability of the nanocomplexes was demonstrated, both in vitro by confocal microscopy and in vivo by fluorescence imaging, to be driven by an inherent property of the residual PBA. Ligand competition assays with free PBA pre-treatment demonstrated the targeting effect of the residual PBA from the nanocomplexes 2 and 4. Finally, the nanocomplexes 2 and 4, compared with the free DOX, exhibited significantly greater anti-cancer effects in vitro and even in vivo. Our pPBA-DOX nanocomplex enables a new paradigm for self-assembled nanostructures with potential biomedical applications.


Two mechanisms for the meperidine block of action potential production in frog's skeletal muscle; non-specific and opiate drug receptor mediated blockade.
The effects of meperidine and naloxone, and their interaction effects on action potential production in frog's sartorius muscle fibres, were studied with intracellular micro-electrode techniques. 1. Meperidine, a narcotic analgesic drug, depressed the rate of rise, the rate of fall and the amplitude of the action potentials. 2. At a meperidine concentration of 0-35 mM, the depression in the action potential maximum rate of rise followed a diphasic time course. At first there was a rapid reduction in the maximum rate of rise which was levelling off at about 60% of control 60-90 min after drug application. This was followed by the second phase during which there was an initial rapid decrease in the maximum rate of rise and all surface fibres were inexcitable by 180 min. 3. The addition of naloxone, a narcotic antagonist, in low concentrations (3 X 10(-5) to 3 X 10(-4) mM) at 70-90 min blocked the second phase of the meperidine-induced depression. 4. With lower concentrations of meperidine (0-18 and 0-07 mM) the depression usually developed more slowly (up to 6 hr with the latter dose) and the addition of low naloxone concentrations partially antagonized the effects of meperidine. However, under no conditions was it possible to completely antagonize the effects of meperidine by the addition of naloxone. 5. A linear relation was found between action potential amplitude and the action potential maximum rate of fall. 6. Meperidine caused a shift in the relation of rate of fall against amplitude to higher action potential amplitudes, indicating that the drug inhibited the increase in potassium conductivity (gK) associated with the falling phase of the action potential. 7. When low naloxone concentrations antagonized the effects of meperidine on the rate of rise and restored action potential amplitudes to control levels, the effect of meperidine on the maximum rate of fall was not antagonized. 8. Larger naloxone concentrations (1-5 X 10(-2) mM or more) depressed the action potential rate of rise but did not alter the relation between action potential amplitude and the maximum rate of fall. 9. It is proposed that meperidine blocks action potential production by two mechanisms: (i) a non-specific mechanism in which the increases in both gNa and gK ar depressed and (ii) an opiate drug receptor mediated mechanism causing a specific depression of gNa. 10. The impression gained from the results is that there are opiate drug receptors located on the inner surface of the muscle membrane associated with the 'sodium channels' and that drug activation of these receptors by either meperidine or high naloxone concentrations interferes with the opening of the 'sodium channels' normally produced by membrane depolarization.


Surgical versus nonsurgical therapy for lumbar spinal stenosis.
Surgery for spinal stenosis is widely performed, but its effectiveness as compared with nonsurgical treatment has not been shown in controlled trials. Surgical candidates with a history of at least 12 weeks of symptoms and spinal stenosis without spondylolisthesis (as confirmed on imaging) were enrolled in either a randomized cohort or an observational cohort at 13 U.S. spine clinics. Treatment was decompressive surgery or usual nonsurgical care. The primary outcomes were measures of bodily pain and physical function on the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36) and the modified Oswestry Disability Index at 6 weeks, 3 months, 6 months, and 1 and 2 years. A total of 289 patients were enrolled in the randomized cohort, and 365 patients were enrolled in the observational cohort. At 2 years, 67% of patients who were randomly assigned to surgery had undergone surgery, whereas 43% of those who were randomly assigned to receive nonsurgical care had also undergone surgery. Despite the high level of nonadherence, the intention-to-treat analysis of the randomized cohort showed a significant treatment effect favoring surgery on the SF-36 scale for bodily pain, with a mean difference in change from baseline of 7.8 (95% confidence interval, 1.5 to 14.1); however, there was no significant difference in scores on physical function or on the Oswestry Disability Index. The as-treated analysis, which combined both cohorts and was adjusted for potential confounders, showed a significant advantage for surgery by 3 months for all primary outcomes; these changes remained significant at 2 years. In the combined as-treated analysis, patients who underwent surgery showed significantly more improvement in all primary outcomes than did patients who were treated nonsurgically. (ClinicalTrials.gov number, NCT00000411 [ClinicalTrials.gov].).


A revised mathematical model of cerebral microischemia.
Cerebral microinfarcts (lacunes) are considered to cause dementia. Experimental studies of this kind of infarct may bring us closer to an understanding of, and thus, a treatment for, cerebral infarction. However, the study of experimental cerebral microischemia is complex because of the high resolution needed. Comparing experimental with theoretical results should improve our knowledge of the subject. In the present work, a theoretical model of cerebral microischemia was improved and some results are presented. This study confirms that the glucose supply in some cases limits the energy turnover. Furthermore, the results show that increasing the oxygen supply (increasing Khem, and increasing the partial pressure of oxygen in blood) should at maximum only improve the energy turnover by about 5%. The present model may be an aid in the interpretation of experimental results and may be used to predict benefits of various treatments.


[The use of antiadhesins--a new prospective trend in preventing and treating infectious diseases (a foundation for the technologies for creating drugs in the 21st century)].
The state and prospects of research on creation of antiadhesins--new generation drugs for preventing and treatment of infectious diseases, are analyzed in the paper. The elaboration of such drugs is based on the profound knowledge about the nature of viral, bacterial, fungal and other infectious agents of diseases, molecular mechanisms of their interactions with the affected organs and tissues which are based on the processes of carbohydrate-protein recognizing. Rapid development of such fields of science as glycobiology and lectinology has created the preconditions for artificial synthesis of oligosaccharides which mimicked the receptors and can interact with adhesive structures of the disease agents more intensively than their natural analogs and block them. This makes the interaction of the latter with the affected organs impossible. The intensive work on elaboration of natural drugs: antiadhesins, is carried out in most countries. Adhesins are not harmful for people and cannot provoke the development of resistance to them in the disease agents. Till recently Ukraine belonged to the number of countries where the fields of science mentioned above were intensively developed but, in connection with the present stagnation of science and even the artificial hindering of its development, the country gradually losses the position of a leader. Hence, one can conclude that when 10-15 years later the market of pharmaceutical products will be filled with antiadhesins, our country will not be on the list of their producers, if the authorities will spend funds to buy foreign drugs as before instead of stimulating the development and production of the home ones.


Relation of troponin elevation to outcome in patients with infective endocarditis.
Elevated troponin is increasingly recognized as a marker of cardiac injury and poor outcomes in diverse disease states. It was hypothesized that patients with infective endocarditis (IE) and elevated cardiac troponin would have more extensive IE and worse clinical outcomes. Patients were enrolled as part of the International Collaboration on Endocarditis (ICE) prospective cohort study; analysis of these patients was done retrospectively. Data from 83 consecutively enrolled patients from a single center were evaluated. Cardiac troponin I (cTnI) was drawn for clinical indications and before any cardiac surgery in 51 of the 83 patients. Outcomes evaluated were hospital mortality, annular or myocardial abscess on the basis of echocardiography or surgery, and central nervous system events. Of 51 patients with cTnI drawn, 33 (65%) had elevated cTnI > or =0.1 mg/dl. There were no differences in age, gender, prosthetic valve IE, Staphylococcus aureus IE, or history of coronary artery disease, congestive heart failure, or diabetes mellitus between patients with and without cTnI elevations. Patients with elevated cTnI were less likely to have isolated right-sided IE and more likely to have left ventricular systolic dysfunction or renal dysfunction (p <0.05 for each). In conclusion, elevated cTnI was associated with the composite of death, abscess, and central nervous system events (p <0.001).


Illness Perceptions and Quality of Life in Patients with Non-Small-Cell Lung Cancer: A 3-Month Follow-Up Pilot Study.
Examine illness perceptions, functional health and quality of life of lung cancer patients throughout chemotherapy treatment. Longitudinal design with baseline measure 12 days after the first chemotherapy and follow-up measure 3 months later, where illness perceptions (BIPQ), functional health, and quality of life (EORTC QLQ-C-30) were measured. A total of 21 patients with non-small-cell lung cancer took part. Non-parametric testing was performed given the pilot nature of the study and the associated relatively small sample size. Small to medium changes in illness perceptions and functional health between the two measurement points were detected, with both becoming more positive. More negative illness perceptions at the beginning of the treatment were associated with less functioning and lower quality of life at both beginning and end of treatment. Addressing illness perceptions seems a clinically relevant approach in improving functioning and quality of life of patients with non-small-cell lung cancer.


The protective mechanism of Nigella sativa against diethylnitrosamine-induced hepatocellular carcinoma through its antioxidant effect and EGFR/ERK1/2 signaling.
A wide variety of natural products have powerful chemopreventive effects due to their antioxidant, antimutagenic, and anti-inflammatory activities that enable them to arrest cell proliferation in several cancer models. In the present study, we shed light on the protective mechanism of Nigella sativa extract against diethylnitrosamine (DENA)-induced preneoplastic stage of hepatocellular carcinoma (HCC) in rats. We studied the extract effect on EGFR/ERK1/2 signaling pathway as one of the major signaling pathways controlling cell proliferation during hepatocarcinogenesis as well as the investigation of its antioxidant activity. The study also compared the effects of NSEE to those of (thymoquinone) TQ and silymarin as hepatoprotective substances. Rats received daily doses of NSEE (150, 250, 350 mg/kg BW), a dose per three alternative days/week of TQ (20 mg/kg BW) and a daily dose of silymarin (100 mg/kg BW). The doses were administered orally by gavage for 12 days before DENA and CCl4 administration, and then the supply of NSEE, TQ or silymarin was continued until the end of the experiment (16 weeks). DENA administration activated EGFR/ERK1/2 signaling and caused a significant increase in P-EGFR and P-ERK1/2 as well as a significant up-regulation of expression of target genes such as PCNA, c-fos and Bcl2, which indicated the increase in cell proliferation. Furthermore, a significant elevation in alpha-fetoprotein (AFP) and hepatic enzymes was observed in DENA-treated rats in addition to a decrease in the antioxidant status. The protection with NSEE, TQ, or silymarin has the potential to inhibit the EGFR/ERK1/2 activation and improve the antioxidant status. Moreover, the action of NSEE against the hepatocarcinogenesis was supported by high antioxidant activity and the histopathological observations of the liver. These data suggest that NSEE has a chemopreventive role in DENA-induced HCC through the inhibition of the EGFR/ERK1/2 signaling pathway and their target genes in addition to its role as an antioxidant.


Impact of rpoB mutations on reduced vancomycin susceptibility in Staphylococcus aureus.
Of 38 vancomycin-intermediate Staphylococcus aureus (VISA) clinical strains, 27 (71%) possessed a mutation(s) in rpoB encoding the β-subunit of RNA polymerase. Furthermore, 95.6% of the rifampin-resistant mutants obtained from 9 methicillin-resistant S. aureus (MRSA) clinical isolates showed decreased vancomycin susceptibilities. These data indicate the involvement of an rpoB mutation in VISA phenotype expression.


Loss of liver-intestine cadherin in human intrahepatic cholangiocarcinoma promotes angiogenesis by up-regulating metal-responsive transcription factor-1 and placental growth factor.
Liver-intestine cadherin (LI-cadherin) represents a novel type of cadherin within the cadherin superfamily that comprises seven cadherin repeats and a short cytoplasmic domain. In this study, we first examined LI-cadherin expression immunohistochemically in 34 specimens of human intrahepatic cholangiocarcinoma (ICC). LI-cadherin expression was positive (defined as positivity in > or = 10% of cells) in 18 of the ICCs (52.9%). LI-cadherin negativity was significantly correlated with tumor dedifferentiation (P=0.026) and vascular invasion (P=0.015). The cumulative survival rate of patients with LI-cadherin-negative ICC was significantly shorter than that of patients with LI-cadherin-positive ICC (P=0.021). Multivariate analysis identified the extent of LI-cadherin staining as an independent prognostic factor for ICC survival (P=0.027). Next, to elucidate the mechanism of loss of LI-cadherin-mediated aggressiveness in ICC, we knocked down LI-cadherin expression in an ICC cell line using small interfering RNA (siRNA) technology, and screened for genes that were expressed differentially between these cells and ICC cells transfected with scrambled siRNA using microarray analysis with real-time polymerase chain reaction confirmation. Among 21 identified genes, we focused on metal-responsive transcription factor-1 (MTF-1), whose target genes might contribute to tumor aggressiveness. Expression of placental growth factor (PlGF), one of the MTF-1 target genes, was up-regulated in the ICC cells transfected with LI-cadherin siRNA. Likewise, PlGF expression was up-regulated in LI-cadherin-negative ICC specimens. There was a significant inverse relationship between these expressions (P=0.033). Furthermore, the microvessel density of LI-cadherin-negative ICC specimens was higher than that of LI-cadherin-positive specimens. These findings suggest that loss of LI-cadherin in ICC is associated with tumor dedifferentiation and vascular invasion, and thus poor prognosis. Loss of LI-cadherin results in up-regulation of MTF-1 and PlGF, thereby regulating angiogenesis in ICC.


Comparison of quantitative and molecular variation in agroforestry populations of the shea tree (Vitellaria paradoxa C.F. Gaertn) in Mali.
In this study we investigated the within- and between-population genetic variation using microsatellite markers and quantitative traits of the shea tree, Vitellaria paradoxa, an important agroforestry tree species of the Sudano-Sahelian region in Africa. Eleven populations were sampled across Mali and in northern Côte d'Ivoire. Leaf size and form and growth traits were measured in a progeny test at the nursery stage. Eight microsatellites were used to assess neutral genetic variation. Low levels of heterozygosity were recorded (1.6-3.0 alleles/locus; H(E) = 0.25-0.42) and the fixation index (F(IS) = -0.227-0.186) was not significantly different from zero suggesting that Hardy-Weinberg equilibrium is encountered in all populations sampled. Quantitative traits exhibited a strong genetic variation between populations and between families within populations. The degree of population differentiation of the quantitative traits (Q(ST) = 0.055-0.283, Q(STmean) = 0.189) strongly exceeds that in eight microsatellite loci (F(ST) = -0.011-0.142, F(STmean) = 0.047). Global and pairwise F(ST) values were very low and not significantly different from zero suggesting agroforestry practices are amplifying gene flow (Nm = 5.07). The population means for quantitative traits and the rainfall variable were not correlated, showing variation was not linked with this climatic cline. It is suggested that this marked differentiation for quantitative traits, independent of environmental clines and despite a high gene flow, is a result of local adaptation and human selection of shea trees. This process has induced high linkage disequilibrium between underlying loci of polygenic characters.


Extension and customization of self-stability control in compliant legged systems.
Several recent studies on the control of legged locomotion in animal and robot running focus on the influence of different leg parameters on gait stability. In a preceding investigation self-stability controls showing deadbeat behavior could be obtained by studying the dynamics of the system in dependence of the leg orientation carefully adjusted during the flight phase. Such controls allow to accommodate disturbances of the ground level without having to detect them. Here we further this method in two ways. Besides the leg orientation, we allow changes in leg stiffness during flight and show that this extension substantially improves the rejection of ground disturbances. In a human like example the tolerance of random variation in ground level over many steps increased from 3.5% to 35% of leg length. In single steps changes of about 70% leg length (either up or down) could be negotiated. The variable leg stiffness not only allows to start with flat leg orientations maximizing step tolerances but also increase the control subspace. This allows to customize self-stability controls and to consider physical and technical limitations found in animals and robots.


Inflammation is present in de Quervain Disease--correlation study between biochemical and histopathological evaluation.
De Quervain disease is a stenosing condition of the sheath of the abductor pollicis longus and extensor pollicis brevis tendons at the radial styloid process. Previous studies consistently reported that the pathological change of this condition is thought to be primarily an extensor retinaculum thickened by fibrosis and angiogenesis instead of inflammation. Contradictorily, the conservative treatment for de Quervain disease is anti-inflammatory medication. The inflammatory response may be involved in this disease; however, there is no present study directly evidencing whether the inflammatory responses exist in de Quervain disease or not. The histopathology of de Quervain disease is yet to be elucidated clearly. To grade all specimens in the different stages and characterize specific inflammatory cell and factors to examine whether inflammatory response is involved in de Quervain disease. Retinaculum samples were collected from 13 patients with de Quervain disease after surgery. The specimens were evaluated histologically by collagen structure grading and immunohistochemically by quantifying the presence of neutrophil elastase, macrophages, cyclooxygenase, and vascular endothelium. Neutrophil elastase and cyclooxygenase occur in the de Quervain disease retinaculum and increased with the grade of collagen structure. After angiogenesis, macrophage infiltration occurs in the grade II matrix worse than grade III matrix. Inflammation is present in de Quervain disease. This study provides direct evidence for inflammatory cell and infiltration factors and offer valuable clues for specific pharmacological therapies for de Quervain disease.


Copper toxicity thresholds in Chinese soils based on substrate-induced nitrification assay.
Copper toxicity in 17 Chinese soils was screened using a substrate-induced nitrification assay to generate information for the development of a terrestrial biotic ligand model (tBLM). The leaching effect on the Cu toxicity thresholds was investigated. Both the total Cu-based median effective concentration (EC50) values (46.9-2726 mg/kg) and the solution Cu-based EC50 values (0.04-2.91 mg/L) in unleached soils varied substantially among the soils in the present study. For unleached soils, linear stepwise multiple regression analysis showed that total Ca and soil pH were the best predictors for total Cu-based EC50, while electrical conductivity (EC) and soil pH were the best predictors for solution Cu-based EC50. The variation in solution Cu-based EC50 was largely (R(2) = 0.75) explained by Mg but not Ca and H(+) concentration in soil solution at EC50, suggesting a protective effect of Mg(2+) against Cu toxicity in the test soils. Leaching impacted Cu toxicity differently among the soils and apparently reduced the variations of both the total Cu-based and the solution Cu-based EC50. The predictability of the Cu EC50 by empirical models was decreased after leaching. The leaching effect on Cu toxicity, indicated by a leaching factor, was not predicted by any soil properties. There is a need to investigate quantitatively the mechanisms for the leaching effect on Cu toxicity in soils.


Screening for symptoms of depression by physical therapists managing low back pain.
Depression is a condition that worsens the prognosis of low back pain (LBP) and is under-recognized and undertreated in primary care. The purpose of this study was to evaluate the accuracy with which physical therapists screen for depressive symptoms among their patients with LBP. Sixty-eight physical therapists and 232 patients with nonspecific LBP from 40 physical therapy clinics participated. Patients completed the reference standard (Depression Anxiety Stress Scales [DASS]) and a 2-item screening test for depression taken from the Primary Care Evaluation of Mental Disorders Procedure (PRIME-MD). Treating physical therapists used a 0 to 10 scale to judge whether each patient was depressed. Based on the short-form Depression Anxiety Stress Scales (DASS-21) depression scale score, each patient was categorized as exhibiting normal, mild, moderate, severe, or extremely severe depression symptoms, and receiver operating characteristic (ROC) curves were generated to describe test accuracy. The 2-item screening test was more accurate in screening for depressive symptoms than the physical therapists' ratings were; for example, in detecting moderate depressive symptoms in the 2 areas under the ROC curve, values were 0.66 versus 0.79. Because the therapists did not accurately identify symptoms of depression, even symptoms of severe depression, despite the common presentation in their clinics, we recommend that physical therapists managing patients with LBP use the 2-item depression screening test. Administration of this screening test would improve physical therapists' ability to screen for symptoms of depression and would enable referral for appropriate management.


Cardiometabolic health among gastric bypass surgery patients with polycystic ovarian syndrome.
To examine the effect of gastric bypass surgery on cardiometabolic health among women with polycystic ovarian syndrome (PCOS). Retrospective medical chart review identified women (n = 389) with PCOS who underwent Roux-en-Y gastric bypass surgery from 2001-2009 in one surgical practice. Separate repeated measures linear mixed models were fit using the MIXED procedure to assess mean change in cardiometabolic disease risk factors from before to 1-year after surgery and were evaluated by ethnicity [Hispanic, non-Hispanic black (NHB) and white (NHW)]. The majority of the sample was Hispanic (66%, 25% NHB, 9% NHW). Mean body mass index significantly improved 1 year post-surgery for all ethnic groups (45.5 to 35.5 kg/m(2) for Hispanics, 46.8 to 37.7 kg/m(2) for NHB and 45.7 to 36.7 kg/m(2) for NHW, P < 0.001). Among Hispanic women mean total cholesterol (198.1 to 160.2 mg/dL), low-density lipoproteins (LDL) cholesterol (120.9 to 91.0 mg/dL), triglycerides (148.6 to 104.8 mg/dL), hemoglobin A1c (6.2% to 5.6%), alanine aminotransferase (28.1 to 23.0 U/L) and aspartate aminotransferase (23.5 to 21.6 U/L) decreased significantly (P < 0.001). Among NHB, mean total cholesterol (184.5 to 154.7 mg/dL), LDL cholesterol (111.7 to 88.9 mg/dL) and triglycerides (99.7 to 70.0 mg/dL) decreased significantly (P < 0.05). Among NHW, mean total cholesterol (200.9 to 172.8 mg/dL) and LDL cholesterol (124.2 to 96.6 mg/dL), decreased significantly (P < 0.05). Pairwise ethnic group comparisons of all cardiometabolic outcomes adjusted for age and type of surgery before and 1 year after surgery showed no statistical difference between the three groups for any outcome. Cardiometabolic disease risk improvements vary by ethnicity and obesity may impact glucose tolerance and liver function changes more in Hispanic women with PCOS vs non-Hispanic women.


Dynamic brain phantom for intracranial volume measurements.
Knowledge of intracranial ventricular volume is important for the treatment of hydrocephalus, a disease in which cerebrospinal fluid (CSF) accumulates in the brain. Current monitoring options involve MRI or pressure monitors (InSite, Medtronic). However, there are no existing methods for continuous cerebral ventricle volume measurements. In order to test a novel impedance sensor for direct ventricular volume measurements, we present a model that emulates the expansion of the lateral ventricles seen in hydrocephalus. To quantify the ventricular volume, sensor prototypes were fabricated and tested with this experimental model. Fluid was injected and withdrawn cyclically in a controlled manner and volume measurements were tracked over 8 h. Pressure measurements were also comparable to conditions seen clinically. The results from the bench-top model served to calibrate the sensor for preliminary animal experiments. A hydrocephalic rat model was used to validate a scaled-down, microfabricated prototype sensor. CSF was removed from the enlarged ventricles and a dynamic volume decrease was properly recorded. This method of testing new designs on brain phantoms prior to animal experimentation accelerates medical device design by determining sensor specifications and optimization in a rational process.


Virulence determinants of avian H5N1 influenza A virus in mammalian and avian hosts: role of the C-terminal ESEV motif in the viral NS1 protein.
We assessed the prediction that access of the viral NS1 protein to cellular PDZ domain protein networks enhances the virulence of highly pathogenic avian influenza A viruses. The NS1 proteins of most avian influenza viruses bear the C-terminal ligand sequence Glu-Ser-Glu-Val (ESEV) for PDZ domains present in multiple host proteins, whereas no such motif is found in the NS1 homologues of seasonal human virus strains. Previous analysis showed that a C-terminal ESEV motif increases viral virulence when introduced into the NS1 protein of mouse-adapted H1N1 influenza virus. To examine the role of the PDZ domain ligand motif in avian influenza virus virulence, we generated three recombinants, derived from the prototypic H5N1 influenza A/Vietnam/1203/04 virus, expressing NS1 proteins that either have the C-terminal ESEV motif or the human influenza virus RSKV consensus or bear a natural truncation of this motif, respectively. Cell biological analyses showed strong control of NS1 nuclear migration in infected mammalian and avian cells, with only minor differences between the three variants. The ESEV sequence attenuated viral replication on cultured human, murine, and duck cells but not on chicken fibroblasts. However, all three viruses caused highly lethal infections in mice and chickens, with little difference in viral titers in organs, mean lethal dose, or intravenous pathogenicity index. These findings demonstrate that a PDZ domain ligand sequence in NS1 contributes little to the virulence of H5N1 viruses in these hosts, and they indicate that this motif modulates viral replication in a strain- and host-dependent manner.


The association between the social adaptive skills of school-aged children with congenital heart disease and mothers' decision factors for providing disease explanations in Japan: a cross-sectional study.
This study aimed to clarify the factors related to mothers' decisions to provide disease explanations to their children, investigate the associations between those factors and social adaptive skills, and examine support relative to children's growth and development. Data were collected from anonymous, self-administered questionnaires answered by 71 mothers of outpatient school-aged children with congenital heart disease. The questionnaire items included characteristics of mothers and children, decision factors for providing disease explanations, and children's social adaptive skills (Asahide-Shiki social adaptive skills test). Factor analysis was performed on the decision factors, and multiple regression analysis was performed to examine the association between the identified factors and each social adaptive skill. The decision factors for providing disease explanations were the mother's explanation ability, the receptive capability of the child, and the child's interest and literacy regarding the explanation. Multiple regression analysis showed that language and social life skills were significantly associated with the child's receptive capability, and language and daily life skills were significantly associated with the child's interest and literacy regarding the explanation. Improving children's language, social life, and daily life skills may enhance their receptive capability and literacy regarding explanations of their disease.


The Development and Implementation of New Assessment Tools for the Surgical Clerkship Rotation.
This article was migrated. The article was marked as recommended. Innovation: We developed two new rubrics with explicit behavioural anchors to assess students in the Queen's undergraduate medical education (UGME) surgery clerkship rotation. These rotation rubrics, complemented by a new ambulatory clinic encounter card, improved the quality, consistency, and timeliness of feedback for clerks from faculty preceptors. This innovation was introduced during a comprehensive workplace-based assessment re-design being undertaken in the Department of Surgery as part of the transition to a post-graduate competency-based medical education (CBME) system for post-graduate education (PGME). The core UGME working group, comprised of a faculty surgeon, assessment consultant, and a surgical resident, selected terminology and designed the tool visual structure to be similar to the new post-graduate assessment tools, since most preceptors supervise learners in both programs. This consistency enhanced buy-in from faculty and ensured a smooth transition to the use of the new UGME tools. Development: The new assessment process was developed and piloted in three phases: (1) development of an assessment system based on rubrics with explicit behavioural descriptors as the key assessment tools; (2) implementation of a pilot study to establish the acceptability and feasibility of the use of these rubrics, with iterative revisions based on stakeholder feedback; and (3) development of a validity argument for the use of these assessment tools. The latter is scheduled for 2018. Outcomes: The use of these rotation behaviour-anchored rubrics and corresponding ambulatory clinic encounter card has greatly improved the mid- and final-rotation feedback provided to students on the Surgery Clerkship. The concrete, descriptive information provided by the rubrics allows the course director to provide specific feedback during rotation exit meetings. The course director has the ability to clearly articulate to students the areas where they have met (or exceeded) the expected level of competency, as well as areas which require additional attention.


Lung volume reduction surgery: technique, operative mortality, and morbidity.
The objective of lung volume reduction surgery (LVRS) is the safe, effective, and durable palliation of dyspnea in appropriately selected patients with moderate to severe emphysema. Appropriate patient selection and preoperative preparation are prerequisites for successful LVRS. An effective LVRS program requires participation by and communication between experts from pulmonary medicine, thoracic surgery, thoracic anesthesiology, critical care medicine, rehabilitation medicine, respiratory therapy, chest radiology, and nursing. The critical analysis of perioperative outcomes has influenced details of the conduct of the procedure and has established a bilateral, stapled approach as the standard of care for LVRS. The National Emphysema Treatment Trial (NETT) remains the world's largest multi-center, randomized trial comparing LVRS to maximal medical therapy. NETT purposely enrolled a broad spectrum of anatomic patterns of emphysema. This, along with the prospective, audited collection of extensive demographic, physiologic, radiographic, surgical and quality-of-life data, has positioned NETT as the most robust repository of evidence to guide the refinement of patient selection criteria for LVRS, to assist surgeons in providing optimal intraoperative and postoperative care, and to establish benchmarks for survival, complication rates, return to independent living, and durability of response. This article reviews the evolution of current LVRS practice with a particular emphasis on technical aspects of the operation, including the predictors and consequences of its most common complications.


Insulin promotes rat retinal neuronal cell survival in a p70S6K-dependent manner.
The purpose of this study was to examine the role of the ribosomal protein S6 protein kinase (p70S6K), a protein synthesis regulator, in promoting retinal neuronal cell survival. Differentiated R28 rat retinal neuronal cells were used as an experimental model. Cells were maintained in Dulbecco's modified Eagle's medium supplemented with 10% newborn calf serum, and during the period of experimentation were exposed either to the absence or presence of 10 nm insulin. Insulin treatment induced p70S6K, mTOR, and Akt phosphorylation, effects that were completely prevented by the PI3K inhibitor, LY294002. Insulin-induced phosphorylation of p70S6K and mTOR was prevented by the mTOR inhibitor, rapamycin. Apoptosis, induced by serum deprivation and evaluated by Hoechst staining, was inhibited by insulin treatment in R28 cells, but not in L6 muscle cells. This effect of insulin was also largely prevented by rapamycin. Inhibition of p70S6K activity by exogenous expression of a dominant negative mutant of p70S6K prevented insulin-induced cell survival, whereas, overexpression of wild type p70S6K or expression of a rapamycin resistant form of the kinase enhanced the effect of insulin on survival. Enhanced cell survival under the latter condition was accompanied by increased p70S6K activity and phosphorylation. Rapamycin did not inhibit insulin induced p70S6K phosphorylation and activity in cells transfected with the rapamycin-resistant mutant. Together, these results suggest that p70S6K plays a key role in insulin stimulated retinal neuronal cell survival.


Changes in exercise stress echocardiographic parameters before and after transcatheter mitral valve edge-to-edge repair.
The safety and feasibility are still not well known for exercise-induced mitral regurgitation (MR). This study is aimed to assess and compare the hemodynamic and symptomatic changes in patients with significant secondary MR during exercise stress echocardiography (ESE) before and after transcatheter edge-to-edge repair (TEER). The study included a total of 15 patients with secondary MR who underwent ESE before and after TEER using the MitraClip system (Abbott, Abbott Park, IL, USA). Echocardiographic data of ESE were collected both before the procedure and during the follow-up visit at 3 months. During the one-year postoperative observation period, the rate of readmission due to heart failure was 13% (n = 2), with no recorded fatalities. Although no significant differences of ESE data were observed in exercise-induced pulmonary hypertension or cardiac output before and after the repair, the severity of MR was significantly improved after the procedure, both at rest (2 [2-3] vs. 1 [1-2], p = 0.0125) and during ESE (3 [3-3] vs. 1 [1-1], p < 0.0001). Furthermore, the New York Heart Association Functional Classification was improved (3 [3-3] vs. 1 [1-1], p < 0.0001) after treatment. For a supplemental analysis, MR during ESE was significantly improved not only in cases with atrial secondary MR but also in ventricular secondary MR. Transcatheter edge-to-edge repair for exercise-induced MR resulted in a significant improvement in postoperative MR severity and subjective symptoms. These results are novel, as they have not been extensively reported previously, particularly among Japanese patients.


Functional characterization of a second porin isoform in Drosophila melanogaster. DmPorin2 forms voltage-independent cation-selective pores.
Mitochondrial porins or voltage-dependent anion-selective channels are channel-forming proteins mainly found in the mitochondrial outer membrane. Genome sequencing of the fruit fly Drosophila melanogaster revealed the presence of three additional porin-like genes. No functional information was available for the different gene products. In this work we have studied the function of the gene product closest to the known Porin gene (CG17137 coding for DmPorin2). Its coding sequence was expressed in Escherichia coli. The recombinant DmPorin2 protein is able to form channels similar to those formed by DmPorin1 reconstituted in artificial membranes. Furthermore, DmPorin2 is clearly voltage-independent and cation-selective, whereas its counterpart isoform 1 is voltage-dependent and anion-selective. Sequence comparison of the two porin isoforms indicates the exchange of four lysines in DmPorin1 for four glutamic acids in DmPorin2. We have mutated two of them (Glu-66 and Glu-163) to lysines to investigate their role in the functional features of the pore. The mutants E163K and E66K/E163K are endowed with an almost full inversion of the ion selectivity. Both single mutations partially restore the voltage dependence of the pore. We found that an additional effect with the double mutant E66K/E163K was the restoration of voltage dependence. Protein structure predictions highlight a 16 beta-strand pattern, typical for porins. In a three-dimensional model of DmPorin2, Glu-66 and Glu-163 are close to the rim of the channel, on two opposite sides. DmPorin2 is expressed in all the fly tissues and in all the developmental stages tested. Our main conclusions are as follows. 1) The CG17137 gene may express a porin with a functional role in D. melanogaster. 2) We have identified two amino acids of major relevance for the voltage dependence of the porin pore.


Fully automated delineation of the optic radiation for surgical planning using clinically feasible sequences.
Quadrantanopia caused by inadvertent severing of Meyer's Loop of the optic radiation is a well-recognised complication of temporal lobectomy for conditions such as epilepsy. Dissection studies indicate that the anterior extent of Meyer's Loop varies considerably between individuals. Quantifying this for individual patients is thus an important step to improve the safety profile of temporal lobectomies. Previous attempts to delineate Meyer's Loop using diffusion MRI tractography have had difficulty estimating its full anterior extent, required manual ROI placement, and/or relied on advanced diffusion sequences that cannot be acquired routinely in most clinics. Here we present CONSULT: a pipeline that can delineate the optic radiation from raw DICOM data in a completely automated way via a combination of robust pre-processing, segmentation, and alignment stages, plus simple improvements that bolster the efficiency and reliability of standard tractography. We tested CONSULT on 696 scans of predominantly healthy participants (539 unique brains), including both advanced acquisitions and simpler acquisitions that could be acquired in clinically acceptable timeframes. Delineations completed without error in 99.4% of the scans. The distance between Meyer's Loop and the temporal pole closely matched both averages and ranges reported in dissection studies for all tested sequences. Median scan-rescan error of this distance was 1 mm. When tested on two participants with considerable pathology, delineations were successful and realistic. Through this, we demonstrate not only how to identify Meyer's Loop with clinically feasible sequences, but also that this can be achieved without fundamental changes to tractography algorithms or complex post-processing methods.


"Nano-oddities": unusual nucleic acid assemblies for DNA-based nanostructures and nanodevices.
CONSPECTUS: DNA is an attractive polymer building material for nanodevices and nanostructures due to its ability for self-recognition and self-assembly. Assembly relies on the formation of base-specific interactions that allow strands to adopt structures in a controllable fashion. Most DNA-based higher order structures such as DNA cages, 2D and 3D DNA crystals, or origamis are based on DNA double helices stabilized by Watson-Crick complementarity. A number of nonclassical pairing patterns are possible between or among DNA strands; these interactions result in formation of unusual structures that include, but are not limited to, G-quadruplexes, i-motifs, triplexes, and parallel-stranded duplexes. These structures create greater diversity of DNA-based building blocks for nanomaterials and have certain advantages over conventional duplex DNA, such as enhanced thermal stability and sensitivity to chemical stimuli. In this Account, we briefly introduce these alternative DNA structures and describe in detail their utilization in a variety of nanomaterials and nanomachines. The field of DNA "nano-oddities" emerged in the late 1990s when for the first time a DNA nanomachine was designed based on equilibrium between B-DNA and noncanonical, left-handed Z-DNA. Soon after, "proof-of-principle" DNA nanomachines based on several DNA "oddities" were reported. These machines were set in motion by the addition of complementary strands (a principle used by many B-DNA-based nanodevices), by the addition of selected cations, small molecules, or proteins, or by a change in pH or temperature. Today, we have fair understanding of the mechanism of action of these devices, excellent control over their performance, and knowledge of basic principles of their design. pH sensors and pH-controlled devices occupy a central niche in the field. They are usually based on i-motifs or triplex DNA, are amazingly simple, robust, and reversible, and create no waste apart from salt and water. G-quadruplex based nanostructures have unusually high stability, resist DNase and temperature, and display high selectivity toward certain cations. The true power of using these "nano-oddities" comes from combining them with existing nanomaterials (e.g., DNA origami, gold nanoparticles, graphene oxide, or mesoporous silica) and integrating them into existing mechanical and optoelectronic devices. Creating well-structured junctions for these interfaces, finding appropriate applications for the vast numbers of reported "nano-oddities", and proving their biological innocence comprise major challenges in the field. Our Account is not meant to be an all-inclusive review of the field but should give a reader a firm grasp of the current state of DNA nanotechnology based on noncanonical DNA structures.


[Types of consciousness disorders in stroke].
The peculiarities of consciousness disturbances in 289 patients with grave brain stroke were studied. Eight informative clinical syndromes, including the awakeness level, brain stem reflex functions as well as vegetative-visceral functions were described. Two levels and eleven corresponding to them phases of damaged consciousness were singled out. The scale of quantitative estimation of each phase of the consciousness damage was established for practical use by the computer method of plural step by step regression; dynamics of phases was shown also.


Ca-dependent nonsecretory vesicle fusion in a secretory cell.
We have compared Ca-dependent exocytosis in excised giant membrane patches and in whole-cell patch clamp with emphasis on the rat secretory cell line, RBL. Stable patches of 2-4 pF are easily excised from RBL cells after partially disrupting actin cytoskeleton with latrunculin A. Membrane fusion is triggered by switching the patch to a cytoplasmic solution containing 100-200 microM free Ca. Capacitance and amperometric recording show that large secretory granules (SGs) containing serotonin are mostly lost from patches. Small vesicles that are retained (non-SGs) do not release serotonin or other substances detected by amperometry, although their fusion is reduced by tetanus toxin light chain. Non-SG fusion is unaffected by N-ethylmaleimide, phosphatidylinositol-4,5-bis-phosphate (PI(4,5)P(2)) ligands, such as neomycin, a PI-transfer protein that can remove PI from membranes, the PI(3)-kinase inhibitor LY294002 and PI(4,5)P(2), PI(3)P, and PI(4)P antibodies. In patch recordings, but not whole-cell recordings, fusion can be strongly reduced by ATP removal and by the nonspecific PI-kinase inhibitors wortmannin and adenosine. In whole-cell recording, non-SG fusion is strongly reduced by osmotically induced cell swelling, and subsequent recovery after shrinkage is then inhibited by wortmannin. Thus, membrane stretch that occurs during patch formation may be a major cause of differences between excised patch and whole-cell fusion responses. Regarding Ca sensors for non-SG fusion, fusion remains robust in synaptotagmin (Syt) VII-/- mouse embryonic fibroblasts (MEFs), as well as in PLCdelta1, PLC delta1/delta4, and PLCgamma1-/- MEFs. Thus, Syt VII and several PLCs are not required. Furthermore, the Ca dependence of non-SG fusion reflects a lower Ca affinity (K(D) approximately 71 microM) than expected for these C2 domain-containing proteins. In summary, we find that non-SG membrane fusion behaves and is regulated substantially differently from SG fusion, and we have identified an ATP-dependent process that restores non-SG fusion capability after it is perturbed by membrane stretch or cell dilation.


Agreement between drug treatment data and a discharge diagnosis of diabetes mellitus in the elderly.
The authors examined agreement between drug treatment data and a discharge diagnosis of diabetes, considered whether agreement was modified by demographic variables and measures of comorbidity, and evaluated construct validity through consideration of relations with subsequent mortality. The study sample comprised 81,700 residents of New Jersey aged 65-99 years who had prescription drug coverage either through Medicaid or that state's Pharmacy Assistance for the Aged and Disabled program and had at least one hospitalization between July 1, 1989, and June 30, 1991. In this population, 16.4% filled a prescription for insulin or an oral hypoglycemic agent during the 120 days before admission, and 16.3% had a discharge diagnosis of diabetes. Overall agreement between these two indicators was modest (kappa = 0.67, 95% confidence interval 0.66-0.67) and was weaker in those aged 85 years and above (kappa = 0.58, 95% confidence interval 0.56-0.60), those in nursing homes (kappa = 0.42, 95% confidence interval 0.39-0.44), and those with a high level of comorbidity (modified Charlson index > or =5; kappa = 0.59, 95% confidence interval 0.56-0.62). Presence of a diagnosis of diabetes was associated with an apparent 24% reduction in the risk of death during the study interval (p<0.001), while prior treatment for diabetes had little relation to mortality (p = 0.15). These paradoxical associations with mortality and the lower agreement between discharge diagnoses and drug treatments associated with older age, nursing home residence, and comorbidity suggest limitations in the use of claims data to identify diabetes in the elderly.


[Hormonal regulation of lipoprotein metabolism: the role in pathogenesis of coronary heart disease].
The character and role of hormonal dysregulation of lipoprotein metabolism during postprandial hyperlipemia were studied in patients with coronary heart disease (CHD) and hyperthyroidism as compared with healthy subjects. Pronounced hypertriglyceridemia alongside with the decreased high density lipoprotein cholesterol (HDL C) after standard fat load were associated with increased level of insulin and decreased level of cortisol. Moreover, in CHD patients fasting hyperinsulinemia becoming even stronger postprandially resulted in prevalence of antilipolytic action of insulin over lipid-mobilizing effect of cortisol; and an extended postprandial hypertriglyceridemia took place. Patients with hyperthyroidism and low cholesterol level both in atherogenic LDL and antiatherogenic HDL, demonstrated decreased level of apo AI (as in CHD patients) and apo B (three times lower than in CHD patients). Very low ratio of apo B/AI in patients with hyperthyroidism both in fasting and postprandial state was a clear indication of their lipoprotein profile antiatherogeneity. Thus, in patients with hyperthyroidism despite of low HDL C and apo AI levels, antiatherogenic properties of lipoprotein profile are probably determined by very low apo B/AI ratio induced by thyroid hormones, and might be explained by the influence of thyroid hormones on the expression of genes coding these apoproteins.


NO-releasing NSAIDs suppress NF-κB signaling in vitro and in vivo through S-nitrosylation.
NO-NSAIDs are promising anticancer drugs, comprising an NSAID, an NO-releasing moiety, and a spacer linking them. Although the effect of NO-NSAIDs on a wide variety of signaling and other cellular mechanisms has been deciphered, a key question remains unanswered, that being the role of NO to the overall biological effect of these agents. It has been shown that NO can directly modify sulfhydryl residues of proteins through S-nitrosylation and induce apoptosis. We studied 3 NO-NSAIDs having a different NSAID, spacer, and NO-releasing moiety. In vitro: aspirin, NO-ASA, naproxen, and NO-naproxen inhibited HT-29 human colon cancer cell growth, the IC(50)s being >5000, 192±6, 2800±210 and 95±5μM at 24h, respectively. NO-Aspirin and NO-naproxen reduced NF-κB protein levels, and activated caspase-3 enzyme in a dose- and time-dependent manner. Based on the biotin switch assay, NO-ASA and NO-naproxen S-nitrosylated NF-κB p65 in a time-dependent manner. Pretreatment of the cells with carboxy-PTIO, abrogated the S-nitrosylation of NF-κB p65. In vivo: rats treated with NO-ASA, NONO-ASA, and NO-naproxen showed S-nitrosylation of NF-κB p65 in the stomach tissue, increases in plasma TNF-α, and reductions in mucosal PGE(2) levels. These data provide a mechanistic role for NO and a rational for the chemopreventive effects of NO-NSAIDs.


Nodal quasiparticles and antinodal charge ordering in Ca2-xNaxCuO2Cl2.
Understanding the role of competing states in the cuprates is essential for developing a theory for high-temperature superconductivity. We report angle-resolved photoemission spectroscopy experiments which probe the 4a0 x 4a0 charge-ordered state discovered by scanning tunneling microscopy in the lightly doped cuprate superconductor Ca2-xNaxCuO2Cl2. Our measurements reveal a marked dichotomy between the real- and momentum-space probes, for which charge ordering is emphasized in the tunneling measurements and photoemission is most sensitive to excitations near the node of the d-wave superconducting gap. These results emphasize the importance of momentum anisotropy in determining the complex electronic properties of the cuprates and places strong constraints on theoretical models of the charge-ordered state.


Obesity: psychological aspects and management.
The failure of psychological treatments to produce consistent long-term weight loss in obese subjects has led directly to a re-examination of the nature of their eating behaviour and, as stated above, to the development of new theoretical models of obesity. While behavioural therapy techniques have succeeded in producing weight losses in the region of 5 kg on average, and in the short term may be more cost-effective than drug therapy when the patients are seen in groups and by paraprofessionals, many of these subjects regain the weight lost. The majority of treatment methods involve a reduction in food intake most commonly by self-control procedures. Since recent evidence implies that the use of these techniques may derive from false assumptions, a return to individually designed treatments is perhaps the optimum strategy to maximize long-term weight loss (Wooley et al, 1979). It may be necessary to focus on relevant areas involving the wider application of behavioural therapy methods such as anxiety-management training including cue exposure and response prevention. As is most commonly suggested, a change of responses leading inevitably to overeating can be identified. The development of innovative treatment methods for obesity will require an increased understanding by therapists of the role of physiological factors in weight during and following weight loss towards a greater understanding of the factors that for him are likely to be associated with weight gain. Self-reinforcement for maintaining weight and the role of the family in promoting, facilitating, and maintaining weight loss may also be useful. However, the acknowledgement of the role of cognitive factors may eventually lead towards the development of more sophisticated treatment methodologies encompassing physiological aspects of obesity and based on social psychological theories of attitude change.


High inter-individual variation in the gestation length of the hedgehog tenrec, Echinops telfairi (Afrotheria).
The gestation length (GL) of Tenrecs (Tenrecinae, Afrotheria) is still uncertain. This lack of knowledge also applies to the lesser hedgehog tenrec, Echinops telfairi, the species most commonly bred and maintained in captivity. The animals used in this study were held under controlled conditions (light, temperature and humidity). In order to determine the GL, groups of female tenrecs were subjected to various mating procedures followed by isolation periods of different lengths. A total of n=249 pregnancies were analysed and the number of offspring per litter was 3.29+/-0.09. The length of gestation could be determined in n=199 pregnancies and a mean GL of 67.53+/-0.36 days was calculated. Initial attempts with isolation periods of less than 16 days did not allow to accurately define the GL. Experiments with longer isolation periods and females subjected to only one mating procedure (n=10) revealed a variation in the GLs of 57-79 days. However, in one female a GL of only 50 days was also observed indicating an even greater range in GL variation. There was a statistically significant tendency for shorter GLs in the animals that conceived later in the mating season, but no statistical evidence was found that age, parity or litter size played an essential role in determining the GL. In conclusion, an unexpected high variability in gestation length in E. telfairi was demonstrated although the study animals were kept under controlled environmental conditions. The factors and mechanisms regulating this high intra-species variability in gestation length need further investigations.


Immune Correlates of Protection Against Human Cytomegalovirus Acquisition, Replication, and Disease.
Human cytomegalovirus (HCMV) is the most common infectious cause of infant birth defects and an etiology of significant morbidity and mortality in solid organ and hematopoietic stem cell transplant recipients. There is tremendous interest in developing a vaccine or immunotherapeutic to reduce the burden of HCMV-associated disease, yet after nearly a half-century of research and development in this field we remain without such an intervention. Defining immune correlates of protection is a process that enables targeted vaccine/immunotherapeutic discovery and informed evaluation of clinical performance. Outcomes in the HCMV field have previously been measured against a variety of clinical end points, including virus acquisition, systemic replication, and progression to disease. Herein we review immune correlates of protection against each of these end points in turn, showing that control of HCMV likely depends on a combination of innate immune factors, antibodies, and T-cell responses. Furthermore, protective immune responses are heterogeneous, with no single immune parameter predicting protection against all clinical outcomes and stages of HCMV infection. A detailed understanding of protective immune responses for a given clinical end point will inform immunogen selection and guide preclinical and clinical evaluation of vaccines or immunotherapeutics to prevent HCMV-mediated congenital and transplant disease.


Status of pandemic influenza vaccination and factors affecting it in pregnant women in Kahramanmaras, an eastern Mediterranean city of Turkey.
Pregnant women are a target group for receipt of influenza vaccine because there appears to be an elevated mortality and morbidity rate associated with influenza virus infection in pregnant women. The goal of this study is to determine the factors affecting the decisions of pregnant women in Turkey to be vaccinated or not for 2009 H1N1 influenza. We enrolled 314 of 522 (60.2%) pregnant women who attended to the antenatal clinics of the Medical Faculty of Kahramanmaras Sutcuimam University's Department of Gynecology and Obstetrics between December 23, 2009, and February 1, 2010. We developed a 48-question survey which was completed in a face-to-face interview at the clinic with each pregnant woman. Of the 314 pregnant women, 27.4% were in the first trimester, 33.8% were in the second trimester, and 38.8% were in the third trimester. Twenty-eight pregnant women (8.9%) got vaccinated. Of all the women interviewed, 68.5% stated that they were comfortable with their decisions about the vaccine, 7.3% stated they were not comfortable, and 24.2% stated that they were hesitant about their decisions. The probability of receiving the 2009 H1N1 vaccine was 3.46 times higher among working women than housewives, 1.85 times higher among women who have a child than those who do not, and 1.29 times higher among women with a high-school education or higher than those with only a secondary-school education and below. Correct knowledge about the minimal risks associated with receipt of influenza vaccine were associated with a significant increase in the probability of receiving the 2009 H1N1 vaccine. The number of pregnant women in the study group who received the 2009 H1N1 vaccine was very low (8.9%) and two-thirds of them stated that they were comfortable with their decisions concerning the vaccine. Our results may have implications for public health measures to increase the currently low vaccination rate among pregnant women. Further studies are required to confirm whether our findings generalize to other influenza seasons and other settings.


Probiotic lactobacilli inhibit early stages of Candida albicans biofilm development by reducing their growth, cell adhesion, and filamentation.
We evaluated the inhibitory effects of the probiotic Lactobacillus species on different phases of Candida albicans biofilm development. Quantification of biofilm growth and ultrastructural analyses were performed on C. albicans biofilms treated with Lactobacillus rhamnosus, Lactobacillus casei, and Lactobacillus acidophilus planktonic cell suspensions as well as their supernatants. Planktonic lactobacilli induced a significant reduction (p < 0.05) in the number of biofilm cells (25.5-61.8 %) depending on the probiotic strain and the biofilm phase. L. rhamnosus supernatants had no significant effect on the mature biofilm (p > 0.05), but significantly reduced the early stages of Candida biofilm formation (p < 0.01). Microscopic analyses revealed that L. rhamnosus suspensions reduced Candida hyphal differentiation, leading to a predominance of budding growth. All lactobacilli negatively impacted C. albicans yeast-to-hyphae differentiation and biofilm formation. The inhibitory effects of the probiotic Lactobacillus on C. albicans entailed both cell-cell interactions and secretion of exometabolites that may impact on pathogenic attributes associated with C. albicans colonization on host surfaces and yeast filamentation. This study clarifies, for the first time, the mechanics of how Lactobacillus species may antagonize C. albicans host colonization. Our data elucidate the inhibitory mechanisms that define the probiotic candicidal activity of lactobacilli, thus supporting their utility as an adjunctive therapeutic mode against mucosal candidal infections.


Using satellite tobacco mosaic virus vectors for gene silencing.
This unit describes the use of satellite tobacco mosaic virus (STMV) vectors in combination with native TMV particles for inducing transient gene silencing in tobacco plants. Target gene fragment selection and insertion, virus delivery procedures, and phenotype screening of silenced plants are described in detail. All critical parameters for tobacco plant cultivation, virus infection, and RNA silencing efficiency are discussed.


Quantification of BERT Diagnosis Generalizability Across Medical Specialties Using Semantic Dataset Distance.
Deep learning models in healthcare may fail to generalize on data from unseen corpora. Additionally, no quantitative metric exists to tell how existing models will perform on new data. Previous studies demonstrated that NLP models of medical notes generalize variably between institutions, but ignored other levels of healthcare organization. We measured SciBERT diagnosis sentiment classifier generalizability between medical specialties using EHR sentences from MIMIC-III. Models trained on one specialty performed better on internal test sets than mixed or external test sets (mean AUCs 0.92, 0.87, and 0.83, respectively; p = 0.016). When models are trained on more specialties, they have better test performances (p < 1e-4). Model performance on new corpora is directly correlated to the similarity between train and test sentence content (p < 1e-4). Future studies should assess additional axes of generalization to ensure deep learning models fulfil their intended purpose across institutions, specialties, and practices.


Liquid Cell Transmission Electron Microscopy Sheds Light on The Mechanism of Palladium Electrodeposition.
Electrodeposition is widely used to fabricate tunable nanostructured materials in applications ranging from biosensing to energy conversion. A model based on 3D island growth is widely accepted in the explanation of the initial stages of nucleation and growth in electrodeposition. However, there are regions in the electrodeposition parameter space where this model becomes inapplicable. We use liquid cell transmission electron microscopy along with post situ scanning electron microscopy to investigate electrodeposition in this parameter space, focusing on the effect of the supporting electrolyte, and to shed light on the nucleation and growth of palladium. Using a collection of electron microscopy images and current time transients recorded during electrodeposition, we discover that electrochemical aggregative growth, rather than 3D island growth, best describes the electrodeposition process. We then use this model to explain the change in the morphology of palladium electrodeposits from spherical to open clusters with nonspherical morphology when HCl is added to the electrolyte solution. The enhanced understanding of the early stages of palladium nucleation and growth and the role of electrolyte in this process provides a systematic route toward the electrochemical fabrication of nanostructured materials.


Maitake D-Fraction enhances antitumor effects and reduces immunosuppression by mitomycin-C in tumor-bearing mice.
D-Fraction, a polysaccharide extracted from maitake mushrooms (Grifola frondosa), has been reported to exhibit an antitumor effect through activation of immunocompetent cells, including macrophages and T cells, with modulation of the balance between T-helper 1 and 2 cells. We examined whether D-Fraction could decrease the effective dosage of the chemotherapeutic agent, mitomycin-C (MMC), necessary to control carcinoma in mice. We determined that 0.25 mg.kg-1.d-1 was the optimal dosage of MMC because consecutive administration for 17 d resulted in antitumor effects and a survival ratio of 100% in mice bearing mammary cancer cells (MM-46). Although the dosage of MMC was lower than the effective level, spleen weight and total number of nuclear cells in the mouse spleen decreased, indicating that MMC showed immunosuppressive activity. In contrast, the combination of D-Fraction and MMC recovered the decreases in the dose response induced by MMC and inhibited tumor cell growth more than MMC alone. These effects were achieved through increased immunocompetent cell proliferation. We evaluated the expression of CD28 on splenic CD8+ T cells and the amount of interleukin-12 produced by whole spleen cells including macrophages after administering D-Fraction. The results showed enhancement of the T-helper 1 dominant response. These results suggest that D-Fraction can decrease the effective dosage in tumor-bearing mice by increasing the proliferation, differentiation, and activation of immunocompetent cells and thus provide a potential clinical benefit for patients with cancer.


Scopolamine-induced convulsions in fasted mice after food intake: the effect of duration of food deprivation.
It has been shown that mice and rats treated with antimuscarinic drugs, scopolamine or atropine, after fasting for 48 h develop convulsions soon after refeeding. The present study was performed to evaluate whether mice also develop convulsions after being deprived of food for 1-24 h. The effect of day-night fasting on the development of convulsions was also determined in 12-h deprived animals. Mice were deprived of food for periods of 1, 2, 3, 6, 9, 12, 18, 24, and 48 h. Animals fasted for 12 h during the day or night were deprived of food at 08:00 or 20:00 h, respectively. At the time of testing, animals were treated with intraperitoneal (i.p.) saline or 3 mg/kg scopolamine. Twenty minutes later, they were given food and allowed to eat ad lib. All animals were observed for 30 min for the incidence and onset of convulsions. Fasted animals treated with scopolamine developed clonic convulsions after food intake. Incidence of convulsions was significant in 2-, 3-, 12-, 18-, 24-, and 48-h deprived animals. Convulsions observed after deprivation of food for 12 h during the day or at night were almost similar in both regimens. Our results indicate that food deprivation itself, rather than its duration, seems to be the principal factor in the development of these convulsions.


An analysis on organic acids contents in ripe fruits of fifteen Mao Luang (Antidesma bunius) cultivars, harvested from dipterocarp forest of Phupan Valley in northeast Thailand.
This experiment was carried out in the rainy season (May-October) of the 2006 at the Department of Biotechnology, Faculty of Technology, Mahasarakham University, Mahasarakham 44000, Thailand to analyse organic acids contents in ripe fruits of fifteen Mao Luang cultivars harvested from dipterocarp forest, Phupan Valley, Sakon Nakhon, Northeast Thailand. The experiment was laid in a Completely Randomised Design (CRD) with four replications. The fifteen Mao Luang cultivars were used as treatments. The results showed that there were two groups of organic acids contents in ripe fruits of Mao Luang cultivars i.e., major and minor. The major group of organic acids includes: tartaric acid (7.97-12.16 mg g(-1) of fresh weight), ascorbic acid (10.01-16.55 mg g(-1) of fresh weight), citric acid (4.44-11.73 mg g(-1) of fresh weight) and benzoic acid (8.13-17.43 mg g(-1) of fresh weight) and the minor group includes malic acid (3.05-4.52 mg g(-1) of fresh weight), lactic acid (1.12-4.09 mg g(-1) of fresh weight), oxalic acid (1.00-1.45 mg g(-1) of fresh weight) and acetic acid (0.19-0.69 mg g(-1) of fresh weight). Khumlhai cultivar gave the highest amount of ascorbic acid followed by Lompat, Phuchong, Sangkrow 2 and Maelookdog cultivars. Sangkrow 2 and Phuchong cultivars gave the highest ratio between tartaric and malic acids. Total soluble solid content (TSS%) was highest with Sangkrow 5 cultivar, whilst Total Organic Acids (TOA) was highest with Phuchong cultivar and ratio between TSS:TOA was highest with Sangkrow 2 cultivar. Juice % was highest with both Sangkrow 2 and 3 cultivars, whilst Fapratan and Lompat cultivars ranked the second.


Carcinoma of the gallbladder: review of the literature and report on 56 cases at the Beth Israel Medical Center.
Fifty-six patients with carcinoma of the gallbladder were treated at the Beth Israel Medical Center, New York City, during the 17-year period 1969-1987. The disease was most common among elderly women with cholelithiasis. Of the 56, 42 patients (75%) had liver metastases at operation; therefore, the majority underwent only exploratory laparotomy and biopsy. In 50 patients (89%), the tissue diagnosis was adenocarcinoma. Cholecystectomy was performed in 19 patients. Long-term survival occurred in patients with an incidental diagnosis of carcinoma of the gallbladder. The average survival in 44 patients for whom data were available, including long-term survivors, was 20 months. Of this group, 5 patients (11.3%) were still alive 5 years after diagnosis. Excluding those with an incidental diagnosis of gallbladder cancer, 1 patient (2.2%) survived longer than 5 years after diagnosis. Survival data in 3 of 4 patients who underwent extensive surgical treatment, such as liver wedge resection or hepatic lobectomy, averaged 23 months. Although no defined protocols were used, the addition of adjuvant chemotherapy or radiation therapy in patients treated surgically appeared to improve survival. Five patients survived more than 5 years after diagnosis, and 2 patients were alive after 17 years.


Measurement of urinary 8-oxo-7,8-dihydro-2-deoxyguanosine in a novel point-of-care testing device to assess oxidative stress in children.
8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG), also known as 8-hydroxy-2'-deoxyguanosine (8-OHdG), is an oxidatively damaged nucleobases of DNA and is excreted into urine. Therefore, its urinary level is used as a sensitive marker for oxidative stress (OS). Although it can be measured by enzyme-linked immunosorbent assay (ELISA), its application to clinical pediatrics remains limited. Recently, a novel automatic analyzer (model no. ICR-001: Techno Medica Co., Ltd., Japan) has been developed for point-of-care testing (POCT) to measure urinary 8-oxodG. We verified the reliability of the value of urinary 8-oxodG measured by this novel analyzer and to set the age-related reference intervals. We obtained random urine samples from 100 healthy Japanese adults and 157 healthy Japanese children aged 0-15years. Urinary 8-oxodG was determined using two methods: competitive immunochromatography using a novel automatic analyzer (ICR-001) and another was ELISA. Both urinary 8-oxodG and urinary creatinine measured by ICR-001 correlated well with those measured by ELISA (r(s)=0.945, p<0.0001) and an enzymatic method (r(s)=0.988, p<0.0001). Age-related reference for 8-oxodG corrected by creatinine were highest in the youngest subjects and decreased until adolescence, consistent with published data by ELISA. A new automatic analyzer that measures urinary 8-oxodG can be used as a POCT for the assessment of OS levels in children.


Molecular mechanisms of pruritus in prurigo nodularis.
Pruritus is the most common symptom of dermatological disorders, and prurigo nodularis (PN) is notorious for intractable and severe itching. Conventional treatments often yield disappointing outcomes, significantly affecting patients' quality of life and psychological well-being. The pathogenesis of PN is associated with a self-sustained "itch-scratch" vicious cycle. Recent investigations of PN-related itch have partially revealed the intricate interactions within the cutaneous neuroimmune network; however, the underlying mechanism remains undetermined. Itch mediators play a key role in pruritus amplification in PN and understanding their action mechanism will undoubtedly lead to the development of novel targeted antipruritic agents. In this review, we describe a series of pruritogens and receptors involved in mediating itching in PN, including cytokines, neuropeptides, extracellular matrix proteins, vasculogenic substances, ion channels, and intracellular signaling pathways. Moreover, we provide a prospective outlook on potential therapies based on existing findings.


Efficacy and safety of atazanavir/ritonavir-based antiretroviral therapy for HIV-1 infected subjects: a systematic review and meta-analysis.
Atazanavir (ATZ) is a well-tolerated protease inhibitor that can be boosted with ritonavir (r) to treat infection with resistant strains of human immunodeficiency virus 1 (HIV-1). The aim of this meta-analysis was to compare the efficacy, safety, and metabolic effects of ATZ/r regimen versus commonly used antiretroviral drugs such as lopinavir (LPV) and darunavir (DRV) in HIV-1-infected patients. We searched PubMed, Scopus, Embase and Cochrane CENTRAL, using relevant keywords. Data were extracted from eligible randomized trials and pooled as risk ratios (RR) or standardized mean differences (SMD) in a meta-analysis model using RevMan software. Nine randomized controlled trials (RCTs) (3292 patients) were eligible for the final analysis. After 96 weeks of treatment, the pooled effect estimate did not favor either ATZ/r or LPV/r in terms of virological failure rate (RR 1.11, 95% CI [0.74, 1.66]). However, ATZ/r was marginally superior to LPV/r in terms of increasing the proportion of patients with HIV RNA <50 copies/ml (RR 1.09, 95% CI [1.01, 1.17]). The pooled effect estimate did not favor ATZ/r over DRV/r regarding the change in plasma levels of total cholesterol, triglycerides, or high-density lipoprotein at 24, 48, and 96 weeks. Moreover, no significant difference was found between the two regimens (ATZ/r and DRV/r) in terms of change in visceral (SMD -0.06, 95%CI [-0.33, 0.21]) or subcutaneous adipose tissue (SMD 0.12, 95% CI [-0.15, 0.39]). The ATZ/r regimen was generally as effective and well-tolerated as the LPV/r regimen for the treatment of HIV-1 patients. Compared to the DRV/r regimen, ATZ/r has no favorable effect on the plasma lipid profile or adipose tissue distribution.


Comparative Effectiveness of Entecavir Versus Tenofovir for Preventing Hepatocellular Carcinoma in Patients with Chronic Hepatitis B: A Systematic Review and Meta-Analysis.
Chronic hepatitis B (CHB) can lead to hepatocellular carcinoma (HCC). While both tenofovir disoproxil (TDF) and entecavir (ETV) have been shown to reduce the risk of HCC, their comparative effectiveness is unclear. We estimated the comparative effectiveness of these two agents in reducing the risk of HCC in patients with CHB, through a systematic review and meta-analysis. We searched multiple electronic databases from January 1, 1998, to October 31, 2019, for randomized controlled trials and observational comparative effectiveness studies in adults with CHB treated with ETV compared to TDF, reporting the incidence of HCC (minimum follow-up 12 months). Primary outcome was incidence of HCC, calculated as incidence rate ratio (IRR) with 95% confidence interval (CI, unadjusted analysis) and hazard ratio (HR) with 95% CI (adjusted analysis, where reported). Of 1,971 records identified, 14 studies (263,947 person-years) were included for quantitative analysis. On unadjusted meta-analysis of 14 studies, the risk of HCC was not statistically different between ETV and TDF (IRR, 1.28; 95% CI, 0.99-1.66). When using available adjusted data (multivariate or propensity-matched data), the risk of HCC among patients treated with ETV was 27% higher when compared to TDF (seven studies; 95% CI, 1.01-1.60, P = 0.04). Additional analysis of adjusted data when separately reported among patients with cirrhosis demonstrated an adjusted HR of 0.90 (95% CI, 0.66-1.23), suggesting no difference between ETV-treated and TDF-treated groups. The overall confidence in estimates was very low (observational studies, high heterogeneity). TDF may be associated with lower risk of HCC when compared to ETV.


Requirements for the crash protection of older vehicle passengers.
This study compares injury outcomes in vehicle crashes involving different age groups of belted passengers. Two datasets were considered. Firstly, UK national data revealed that younger passengers are much more likely to be involved in crashes per million miles travelled compared to older passengers although older passengers are much more likely to be killed or seriously injured compared to younger passengers. Secondly, in-depth vehicle crash injury data were examined to determine some of the underlying reasons for the enhanced injury risk amongst older passengers. In crashes of approximately equal severity, the older passenger group were significantly more likely to be fatally injured in frontal crashes (p<0.001). However young passengers were as equally likely to be killed in struck-side crashes compared to the older group. The results also showed that older passengers sustained more serious injuries to the chest region in frontal crashes compared with the younger aged group (p<0.0001) and it is this body region that is particularly problematic. When the data were analysed further, it was found that a large proportion of passengers were female and that in the majority of cases, the seat belt was responsible for injury. Since by the year 2030, 1 in 4 persons will be aged over 65 in most OECD countries, the results suggest a need for intervention through vehicle design including in-vehicle crashworthiness systems that take into account reduced tolerance to impact with ageing.