Summary Hepatitis B virus (HBV) causes both acute and chronic hepatitis and infects large numbers of individuals worldwide. Unfortunately, prediction of typical clinical outcome is problematic and ...there is considerable variability in the frequency, duration and severity of disease progression. The mainstay of HBV treatment is directed towards the suppression of HBV replication by nucleos(t)ide analogs (NUCs). The use of immunomodulators such as alpha-Interferon and thymosin alpha1 can, in select patients, results in elimination of both HBsAg and HBeAg. Given the observation that viral clearance is most effective in the presence of a strong immune response, this review summarizes data suggesting that the use of a combination of an immune modulator such as Talpha1 with a highly effective NUC may result in a more successful therapeutic approach in patients with chronic hepatitis B (CHB). Results from small studies using combination Talpha1 and NUCs are encouraging, and ongoing clinical trials combining entecavir with Talpha1 are anticipated to provide important data assessing the use of a combination of Talpha1 with a NUC to achieve resolution of CHB.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Hepatitis B virus (HBV) causes both acute and chronic hepatitis and infects large numbers of individuals worldwide. Unfortunately, prediction of typical clinical outcome is problematic and ...there is considerable variability in the frequency, duration and severity of disease progression. The mainstay of HBV treatment is directed towards the suppression of HBV replication by nucleos(t)ide analogs (NUCs). The use of immunomodulators such as α‐Interferon and thymosin α1 can, in select patients, results in elimination of both HBsAg and HBeAg. Given the observation that viral clearance is most effective in the presence of a strong immune response, this review summarizes data suggesting that the use of a combination of an immune modulator such as Tα1 with a highly effective NUC may result in a more successful therapeutic approach in patients with chronic hepatitis B (CHB). Results from small studies using combination Tα1 and NUCs are encouraging, and ongoing clinical trials combining entecavir with Tα1 are anticipated to provide important data assessing the use of a combination of Tα1 with a NUC to achieve resolution of CHB.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Alternative reproductive tactics (ARTs) can generate considerable within-species life history variation but are often overlooked. Here, we use the invasive round goby (Neogobius melanostomus) to ...address a number of ecological and evolutionary questions about ARTs. Making use of a 12-year, multisite Laurentian Great Lakes data set, we show that the guarder male tactic was twice as common as the sneaker male tactic but that nonreproductive males were the most common morph. The ratio of guarder to sneaker males did not vary spatially despite a wide range of resource densities across sites. Guarders and sneakers spanned similar age ranges, suggesting that the ARTs are nonsequentially expressed. Based on short-term (gut contents) diet analyses, both reproductive tactics consumed fewer types of food and tended to consume fewer items overall when compared with nonreproductive males. Long-term (isotope) diet analyses showed that guarder males fed at a higher trophic level (higher δ
15
N) and had a broader isotopic niche. Our results show that ARTs are an important aspect of this invasive species’ breeding system and should be accounted for when assessing and managing populations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The complications discussed with patients by surgeons prior to surgery vary, because no consensus on major complications exists. Such consensus may improve informed consent and shared ...decision-making. This study aimed to achieve consensus among vascular surgeons on which complications are considered ‘major’ and which ‘minor,’ following surgery for abdominal aortic aneurysm (AAA), carotid artery disease (CAD) and peripheral artery disease (PAD).
Methods
Complications following vascular surgery were extracted from Cochrane reviews, national guidelines, and reporting standards. Vascular surgeons from Europe and North America rated complications as major or minor on five-point Likert scales via an electronic Delphi method. Consensus was reached if ≥ 80% of participants scored 1 or 2 (minor) or 4 or 5 (major).
Results
Participants reached consensus on 9–12 major and 6–10 minor complications per disease. Myocardial infarction, stroke, renal failure and allergic reactions were considered to be major complications of all three diseases. All other major complications were treatment specific or dependent on disease severity, e.g., spinal cord ischemia, rupture following AAA repair, stroke for CAD or deep wound infection for PAD.
Conclusion
Vascular surgeons reached international consensus on major and minor complications following AAA, CAD and PAD treatment. This consensus may be helpful in harmonizing the information patients receive and improving standardization of the informed consent procedure. Since major complications differed between diseases, consensus on disease-specific complications to be discussed with patients is necessary.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background and purpose: Female sexual arousal consists of a number of physiological responses resulting from increased genital blood. Vasoactive intestinal peptide (VIP), neuropeptide Y and to a ...lesser extent nitric oxide are neurotransmitters found in the vasculature of the genitalia. Neutral endopeptidase (NEP) modulates the activity of neuropeptides including VIP. The aim of this study was to investigate the control of genital blood flow by VIP and endogenous neuropeptides using a selective NEP inhibitor UK‐414,495, ((R)‐2‐({1‐(5‐ethyl‐1,3,4‐thiadiazol‐2‐yl) carbamoylcyclopentyl}methyl) valeric acid).
Experimental approach: Vaginal and clitoral blood flow (VBF and CBF) were monitored using laser Doppler in terminally anaesthetized New Zealand rabbits. Increases in VBF and CBF were induced by either electrical stimulation of the pelvic nerve or by i.v. infusion of VIP.
Key results: Stimulation of the pelvic nerve increased VBF and CBF, compared with basal flow. Increases were mimicked by infusion of exogenous VIP. UK‐414,495 dose‐dependently potentiated pelvic nerve‐stimulated increases in VBF (EC50= 37 ± 9 nM; 3.6 × IC50 rabbit NEP). Nerve‐stimulated increases in VBF and CBF were both enhanced after UK‐414,495. UK‐414,495 increased the amplitude and duration of VIP‐induced increases in VBF. UK‐414,495 had no effect on basal VBF or cardiovascular parameters.
Conclusions and implications: Inhibition of NEP potentiates pelvic nerve‐stimulated increases in genital blood flow. This suggests that the endogenous neurotransmitter mediating genital blood flow is a substrate for NEP (most likely VIP). NEP inhibitors may restore sexual arousal in women adversely affected by female sexual arousal disorder.
This article is commented on by Angulo, pp. 48–50 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00693.x
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Hypothermia has been shown to be neuroprotective in some newborns with moderate-to-severe perinatal hypoxic-ischemic encephalopathy (HIE). In 2006, the American Academy of Pediatrics recommended that ...institutions that choose to use therapeutic hypothermia do so in the context of a rigorous protocol, with systematic collection of patient data including neurodevelopmental follow-up. In this report, we describe our experience with implementation of a 'Hypothermia for HIE' program in a single tertiary care Neonatal Intensive Care Unit (NICU). Important components of the program include detailed protocols, staff and outreach education, early initiation of cooling in both inborn and outborn patients, maintaining stable hypothermia during neonatal transport, and comprehensive neurologic evaluation including serial EEGs, brain MRI and neurodevelopmental follow-up. In the first 2 years of the program, we have used hypothermia therapy in 21 patients, 18 with perinatal and 3 with early postnatal events leading to HIE. Eleven of fifteen outborn patients were cooled prior to and during transport, resulting in initiation of therapy 3 h sooner than if therapy had been delayed until arrival at our center. While lowering the body temperature of encephalopathic newborns is not difficult, addressing the complex medical problems of this vulnerable group of patients requires an experienced multidisciplinary team in regional referral centers.
We have employed time-resolved X-ray diffraction with picosecond temporal resolution to measure the time-dependent rocking curves of laser-irradiated asymmetrically cut single InSb crystals. Coherent ...acoustic phonons were excited in the crystals by irradiation with 800-nm, 100-fs laser pulses at irradiances between 0.25 and 12 mJ/cm. The induced time-dependent strain profiles (corresponding to the coherent phonons) were monitored by diffracting collimated, monochromatic pulses of X-rays from the irradiated crystals. Recording of the diffracted radiation with a fast low-jitter X-ray streak camera resulted in an overall temporal resolution of better than 2 ps. The strain associated with the coherent phonons modifies the rocking curve of the crystal in a time-dependent manner, and the rocking curve is recorded by keeping the angle of incidence of the X-rays upon the crystal fixed, but varying the energy of the incident X-rays around a central energy of 8.453 keV (corresponding to the peak of the rocking curve of the unperturbed crystal). The observed time-dependent diffraction from the irradiated crystals is in reasonable agreement with simulations over a wide range of energies from the unperturbed rocking-curve peak.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Expression of the Msx-1 and Msx-2 homeobox genes have been shown to be coordinately regulated with the Bmp-2 and Bmp-4 ligands in a variety of developing tissues. Here we report that transcripts from ...all four genes are developmentally regulated during both foetal and postnatal mammary gland development. The location and time-course of the Bmp and Msx expression point to a role for Msx and Bmp gene products in the control of epithelial-mesenchymal interactions. Expression of Msx-2, but not Msx-1, Bmp-2 or Bmp-4 was decreased following ovariectomy, while expression of the human Msx-2 homologue was regulated by 17beta-oestradiol in the MCF-7 breast cancer cell line. The regulation of Msx-2 expression by oestrogen raises the possibility that hormonal regulation of mammary development is mediated through the control of epithelial-mesenchymal interactions.
African Americans (AA) in the US are twice as likely to be infected with hepatitis C virus (HCV) compared to the non-Hispanic-white US population (Cau). They are also more likely to be infected with ...HCV genotype 1, more likely to develop hepatocellular carcinoma, and, in addition, have a lower response rate to interferon-based therapies. With the increase in response rates reported for combinations of direct-acting antivirals, the possibility that racial disparity would be eliminated by agents that directly inhibit virus replication has become a reality. The objective of this review is to evaluate the literature from clinical studies and retrospective analysis with respect to the response of AA to the most prescribed antiviral combination sofosbuvir plus ledipasvir. While few studies have focused on AA patients, sufficient information is availed from the literature and studies in our predominately AA clinic population to confirm that ledipasvir-sofosbuvir has a similar effectiveness in AA as compared to Cau.
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