Comparison of risk scores for predicting intravenous immunoglobulin resistance in Taiwanese patients with Kawasaki disease.
Kawasaki disease (KD) is the most common type of acquired heart disease in children, and intravenous immunoglobulin (IVIG) therapy is the preferred treatment. Several risk scoring systems have been developed to predict IVIG resistance, which is important in KD management, including the Kobayashi, Egami, and Formosa scores. We evaluated the performance of these scoring systems with a KD patient cohort from Taiwan. We retrospectively analyzed the medical records of all KD patients admitted to our institution from 2012 to 2017. We compared the characteristics of IVIG-resistant and non-resistant patients and evaluated the predictive ability of the scoring systems for IVIG resistance. We included 84 patients, with 73 receiving IVIG therapy. Eight patients were unresponsive to the first IVIG course. Compared to those with good response to therapy or spontaneous improvement, IVIG-resistant patients had a higher C-reactive protein level (16.1 mg/dL vs. 8.6 mg/dL, p < 0.001), higher percentage of segmented leukocytes (75.7% vs. 61.7%, p = 0.008), and lower albumin level (2.98 mg/dL vs. 3.78 mg/dL, p = 0.001). In determining IVIG resistance, the sensitivity and specificity varied among scoring systems (Kobayashi, 37.5% and 86.8%; Egami, 37.5% and 84.2%; and Formosa, 87.5% and 73.7%, respectively). The positive and negative predictive values of the Formosa score were 25.9% and 98.2%, respectively. The Formosa score had the highest sensitivity in determining IVIG resistance. Although the positive predictive value was low, the negative predictive value could reach 98.2%. The Formosa score was superior to other scoring systems in predicting IVIG resistance in Taiwanese KD patients.


Synthesis and binding affinity of an iodinated juvenile hormone.
The synthesis of the first iodinated juvenile hormone (JH) in enantiomerically enriched form is reported. This chiral compound, 12-iodo-JH I, has an iodine atom replacing a methyl group of the natural insect juvenile hormone, JH I, which is important in regulating morphogenesis and reproduction in the Lepidoptera. The unlabeled compound shows approximately 10% of the relative binding affinity for the larval hemolymph JH binding protein (JHBP) of Manduca sexta, which specifically binds natural 3H-10R,11S-JH I (labeled at 58 Ci/mmol) with a KD of 8 X 10(-8) M. It is also approximately one-tenth as biologically active as JH I in the black Manduca and epidermal commitment assays. The 12-hydroxy and 12-oxo compounds are poor competitors and are also biologically inactive. The radioiodinated [125I]12-iodo-JH I can be prepared in low yield at greater than 2500 Ci/mmol by nucleophilic displacement using no-carrier-added 125I-labeled sodium iodide in acetone; however, synthesis using sodium iodide carrier to give the approximately 50 Ci/mmol radioiodinated ligand proceeds in higher radiochemical yield with fewer by-products and provides a radioligand which is more readily handled in binding assays. The KD of [125I]12-iodo-JH I was determined for hemolymph JHBP of three insects: M. sexta, 795 nM; Galleria mellonella, 47 nM; Locusta migratoria, 77 nM. The selectivity of 12-iodo-JH I for the 32-kDa JHBP of M. sexta was demonstrated by direct autoradiography of a native polyacrylamide gel electrophoresis gel of larval hemolymph incubated with the radioiodinated ligand. Thus, the in vitro and in vivo activity of 12-iodo-JH I indicate that it can serve as an important new gamma-emitting probe in the search for JH receptor proteins in target tissues.


Coassembly of hypoxia-sensitive macrocyclic amphiphiles and extracellular vesicles for targeted kidney injury imaging and therapy.
Hypoxia is a major contributor to global kidney diseases. Targeting hypoxia is a promising therapeutic option against both acute kidney injury and chronic kidney disease; however, an effective strategy that can achieve simultaneous targeted kidney hypoxia imaging and therapy has yet to be established. Herein, we fabricated a unique nano-sized hypoxia-sensitive coassembly (Pc/C5A@EVs) via molecular recognition and self-assembly, which is composed of the macrocyclic amphiphile C5A, the commercial dye sulfonated aluminum phthalocyanine (Pc) and mesenchymal stem cell-excreted extracellular vesicles (MSC-EVs). In murine models of unilateral or bilateral ischemia/reperfusion injury, MSC-EVs protected the Pc/C5A complex from immune metabolism, prolonged the circulation time of the complex, and specifically led Pc/C5A to hypoxic kidneys via surface integrin receptor α4β1 and αLβ2, where Pc/C5A released the near-infrared fluorescence of Pc and achieved enhanced hypoxia-sensitive imaging. Meanwhile, the coassembly significantly recovered kidney function by attenuating cell apoptosis, inhibiting the progression of renal fibrosis and reducing tubulointerstitial inflammation. Mechanistically, the Pc/C5A coassembly induced M1-to-M2 macrophage transition by inhibiting the HIF-1α expression in hypoxic renal tubular epithelial cells (TECs) and downstream NF-κB signaling pathway to exert their regenerative effects. This synergetic nanoscale coassembly with great translational potential provides a novel strategy for precise kidney hypoxia diagnosis and efficient kidney injury treatment. Furthermore, our strategy of coassembling exogenous macrocyclic receptors with endogenous cell-derived membranous structures may offer a functional platform to address multiple clinical needs.


Exploring medication safety structures and processes in nursing homes: a cross-sectional study.
Medication safety is important to limit adverse events for nursing home residents. Several factors, such as interprofessional collaboration with pharmacists and medication reviews, have been shown in the literature to influence medication safety processes. This study had three main objectives: (1) To assess how facility- and unit-level organization and infrastructure are related to medication use processes; (2) To determine the extent of medication safety-relevant processes; and (3) To explore pharmacies' and pharmacists' involvement in nursing homes' medication-related processes. Cross-sectional multicenter survey data (2018-2019) from a convenience sample of 118 Swiss nursing homes were used. Data were collected on facility and unit characteristics, pharmacy services, as well as medication safety-related structures and processes. Descriptive statistics were used. Most of the participating nursing homes (93.2%) had electronic resident health record systems that supported medication safety in various ways (e.g., medication lists, interaction checks). Electronic data exchanges with outside partners such as pharmacies or physicians were available for fewer than half (10.2-46.3%, depending on the partner). Pharmacists collaborating with nursing homes were mainly involved in logistical support. Medication reviews were reportedly conducted regularly in two-thirds of facilities. A high proportion of Swiss nursing homes have implemented diverse processes and structures that support medication use and safety for residents; however, their collaboration with pharmacists remains relatively limited.


Effects of metal and predator stressors in larval southern toads (Anaxyrus terrestris).
Natural and anthropogenic stressors typically do not occur in isolation; therefore, understanding ecological risk of contaminant exposure should account for potential interactions of multiple stressors. Realistically, common contaminants can also occur chronically in the environment. Because parental exposure to stressors may cause transgenerational effects on offspring, affecting their ability to cope with the same or novel environmental stressors, the exposure histories of generations preceding that being tested should be considered. To examine multiple stressor and parental exposure effects we employed a 2 × 2 × 2 factorial design in outdoor 1000-L mesocosms (n = 24). Larval southern toads (Anaxyrus terrestris), bred from parents collected from reference and metal-contaminated sites, were exposed to two levels of both an anthropogenic (copper-0, 30 µg/L Cu) and natural (predator cue - present/absent) stressor and reared to metamorphosis. Toads from the metal-contaminated parental source population were smaller at metamorphosis and had delayed development; i.e., a prolonged larval period. Similarly, larval Cu exposure also reduced size at metamorphosis and prolonged the larval period. We, additionally, observed a significant interaction between larval Cu and predator-cue exposure on larval period, wherein delayed emergence was only present in the 30-µg/L Cu treatments in the absence of predator cues. The presence of parental effects as well as an interaction between aquatic stressors on commonly measured endpoints highlight the importance of conducting multistressor studies across generations to obtain data that are more relevant to field conditions in order to determine population-level effects of contaminant exposure.


A novel soft surimi gel with functionality prepared using alcalase for people suffering from dysphagia.
In this study, effects of alcalase on physical properties, pepsin digestibility, and antioxidative activity in the heat-induced surimi gel were investigated to develop a novel gel product for people with dysphagia. The heat-induced gelation profile of surimi showed that alcalase activity was maximized at approximately 37 °C. The surimi gel attained an appropriate texture for people with dysphagia, when a combination of 0.3-0.5% alcalase and two-step heating at 37 °C and 90 °C was used. Adding alcalase effectively promoted proteolysis, resulting in softening of the gel. Furthermore, the gel with 0.5% alcalase showed improved pepsin digestibility, when heated at 37 °C and 90 °C. Its antioxidative activity was enhanced by adding 0.5% alcalase. Therefore, a combination of 0.5% alcalase and the two-step heating at 37 °C and 90 °C was useful in improving the physical and functional properties of the surimi gel for people with dysphagia.


A randomized prospective trial of radical (Halsted) mastectomy versus modified radical mastectomy in 311 breast cancer patients.
This study reports the results of a prospectively randomized trial for treatment of carcinoma of the breast comparing standard (Halsted) radical mastectomy to a modified radical mastectomy. Three hundred eleven patients with primary operable carcinoma of the breast were entered in a surgical and adjunctive chemotherapy trial in Alabama between 1975 and 1978. A total of 91 surgeons participated (all Diplomats of the American Board of Surgery and Members of the American College of Surgeons). All operative reports, pathology and therapy were reviewed by referees. Histologically node positive patients were randomized after operation to receive melphalan or C.M.F.(cytoxan, methotrexate, and 5-FU) for 1 year. After a median follow-up of 5.5 years, there was no significant difference in disease-free survival or in overall survival between the two groups. There was a trend toward improved 5-year survival rates in the radical mastectomy group compared to the modified radical mastectomy group (84% vs. 76%, p = 0.14). There was also an increased incidence of local wound recurrence in those patients receiving modified radical mastectomy, but the differences were not statistically significant (p = 0.09). Longer follow-up will be necessary to evaluate these results more fully.


Identification of octadeca-9,11-dienoic acid and its significance in the diagnosis of cervical intraepithelial neoplasia.
In 1987 it was claimed using high performance liquid chromatography (HPLC) that the molar ratio of octadeca-9,11-dienoic acid to its parent linoleic acid (18:2 (9,12)) was raised in malignant and premalignant conditions of the cervix. In this study based on a gas chromatographic procedure which prevents autoxidation and avoids the detection limitations of HPLC, we have shown that assay of these fatty acids has no role to play in the assessment of cervical neoplasia.


Assumed oxygen consumption frequently results in large errors in the determination of cardiac output.
We sought to investigate the differences in assumed and measured oxygen consumption values for the determination of cardiac output by using the Fick principle in a pediatric population with congenital heart disease. The patient population consisted of 143 patients with a mean age of 11.3 years (age range, 2 days to 23.8 years) undergoing cardiac catheterization during general anesthesia and with mechanical ventilation. Oxygen consumption was measured with a standard commercial analyzing system (Deltatrac II; Datex, Engström, Helsinki, Finland). Assumed oxygen consumption values were calculated according to the formulas of Krovetz and Goldbloom and LaFarge and Miettinen. Comparisons between measurements and assumptions were performed by Bland-Altman plots. Two-sided paired t tests were used to assess a difference of the assumed and measured values. The range of measured oxygen consumption values was between 55.2 and 249 mL . min -1 . m -2 . The Krovetz-Goldbloom formula led to systematically larger values compared with the measured values (P = .0001; mean difference of -53.3 mL . min -1 . m -2 ; 95% confidence interval, -56.7 to -49.8 mL . min -1 . m -2 ). The use of the LaFarge-Miettinen formula tends to overestimate oxygen consumption (P = .0037; mean difference of -15.9 mL . min -1 . m -2 ; 95% confidence interval, -26.5 to -5.4 mL . min -1 . m -2 ). A similarly poor agreement was found when analyzing a subgroup of 25 patients with Fontan-type circulation. The use of assumed instead of measured oxygen consumption values introduces large errors in the determination of cardiac output.


Macular photocoagulation. Optimal wavelength selection.
Relative merits of different laser wavelengths for macular photocoagulation are analyzed in terms of light scattering and light absorption in hemoglobin, melanin, and macular xanthophyll. Disadvantages of inner retinal damage in the macula caused by the blue-green argon photocoagulators in standard clinical use are discussed, along with advantages of argon green and krypton yellow light. Results of treatment of subretinal neovascularization in disciform macular degeneration are presented. A repetitive treatment, close follow-up protocol was employed with the objectives of closing neovasculature and preserving central visual field. In 74 successive patients treated with monochromatic argon green radiation, neovasculature was closed in 93%, central visual field loss was reduced or stabilized in 76%, and visual acuity was improved or stabilized in 70%. Results were analyzed in terms of location and size of the neovascular membrane, and it was found that best results were obtained with neovascularization farther than 600 microns from the foveola and smaller than 2 mm2. In 17 patients with neovascular membranes more than 600 microns from the foveola, neovasculature was closed in 100%, central visual field loss was reduced or stabilized in 94%, and visual acuity was improved or stabilized in 88%. Similar results were obtained with monochromatic krypton yellow radiation.


Lateralized organization of the cerebellum in a silent verbal fluency task: a functional magnetic resonance imaging study in healthy volunteers.
Functionally, the cerebellum is not only involved in motor control but is also thought to influence higher cognitive function including language. Anatomical data would suggest crossed reciprocal connections between the cerebellum and higher order cortical association areas. In the following study, one left- and one right-handed female volunteer underwent functional magnetic resonance imaging in a conventional block design. Regions of activation were detected after performance of a silent verbal fluency task inside the scanner. In the right-handed volunteer we found an activation of the left fronto-parietal cortex and the right cerebellar hemisphere, while in the left-handed volunteer the activation was seen in the right fronto-parieto-temporal cortex and the left cerebellar hemisphere. These initial results demonstrate that cerebellar activation is contralateral to the activation of the frontal cortex even under conditions of different language dominance. They provide evidence for the hypothesis of a lateralized organization of the cerebellum crossed to the cerebral hemispheres in supporting higher cognitive function.


Ultrastructure of the anterior ventral and anterior medial nuclei of the cat thalamus.
Electron microscopical studies of the thalamic AV-AM nuclei substantiated the presence of two main types of neurons, i.e. principal (or relay) cells and Golgi type II interneurons. Characteristic synaptic islands are found in abundance in the AV-AM. Four different types of synaptic terminals have been identified in these islands: RL-boutons = large axonal terminals with round synaptic vesicles; RS-boutons = small axonal terminals with round synaptic vesicles; F1-boutons = small axonal profiles containing flattened synaptic vesicles, and F2-profiles interpreted as presynaptic dendrite appendages, bearing pleomorphic vesicles, both belonging to the Golgi type II interneurons. --The synaptic relations were studied in normal preparations and after lesions in the mamillary body, limbic cortex and hippocampus. The specific afferents (RL-boutons)--originating from the medial mamillary nucleus--are presynaptic to both relay cell dendrites and "presynaptic" dendrite profiles of Golgi type II interneurons, which in turn are presynaptic to the same relay dendrites (synaptic triads). RS-boutons originate mainly from limbic cortex and hippocampus.


Immune dysfunction in the elderly: effect of thymic hormone administration on several in vivo and in vitro immune function parameters.
The effects of short-term thymic hormone administration on age-associated immune function were evaluated. Two groups of individuals greater than 65 years of age were treated for 30 days with thymic extracts (TP1) or placebo; before and after this treatment a panel of in vitro and in vivo parameters was determined according to a very rigorous experimental protocol. In most individuals, TP1 treatment was associated with an improvement in cutaneous delayed-type response to PPD. Moreover, an increase in a circulating T cell subpopulation bearing the CD45R surface antigen ("virgin" T cells), and in NK cell cytotoxic activity was also observed in some subjects. Finally, lymphocyte responsiveness to PHA tended to increase, while no effect on lymphocyte ability to produce IL-2 following mitogen stimulation was observed. These findings suggest that TP1 treatment may influence age-related alterations in immune function parameters in some subjects.


Characteristics and behaviors associated with body image in male domestic violence offenders.
Investigated correlates of body image satisfaction and perceived weight class (underweight, average weight, overweight) in a sample of male domestic violence offenders. Men who identified themselves as either underweight or overweight reported poorer body image satisfaction than those who perceived themselves to be of average weight. Poor body image satisfaction was found to be related to increased risk for both physical and verbal aggression, the tendency to have been a bully and/or a victim of bullying in childhood, and increased alcohol use. Although masculinity was expected to be an important intervening construct, partially explaining the relationship of body image to the major predictor variables, it was not correlated with any of the variables in this study. Finally, perceived weight class was not found to be significantly related to any of the predictor variables.


Impaired oxygenation and increased hemolysis after cardiopulmonary bypass in patients with glucose-6-phosphate dehydrogenase deficiency.
The purpose of this study was to determine whether the damaging effects of cardiopulmonary bypass, ischemia, and reperfusion would be more pronounced in patients with glucose-6-phosphate dehydrogenase deficiency undergoing cardiac surgery. Forty-two patients with glucose-6-phosphate dehydrogenase deficiency underwent open heart procedures using cardiopulmonary bypass. This group was matched with a control group of identical size for comparison of operative course and postoperative outcome. The perioperative variables were compared between the two groups using univariate and multivariate analysis. The duration of ventilation after the operation was significantly longer in the glucose-6-phosphate dehydrogenase-deficient group (13.7 +/- 7.6 hours versus 7.7 +/- 2.8 hours; p < 0.0001). Minimal value of arterial oxygen tension was lower in patients with glucose-6-phosphate dehydrogenase deficiency (66 +/- 12 mm Hg versus 85 +/- 14 mm Hg; p < 0.0001), and more cases of hypoxia (arterial oxygen tension < 60 mm Hg) were found in this group (11 versus 1; p = 0.001). Compared with the control group, patients with glucose-6-phosphate dehydrogenase deficiency had significantly elevated hemolytic indices expressed by bilirubin levels (26 +/- 10 mmol/L versus 17 +/- 6.7 mmol/L; p < 0.0001) and lactic dehydrogenase levels (970 +/- 496 U/L versus 505 +/- 195 U/L; p < 0.0001). They also required significantly more blood transfusion perioperatively (1.9 +/- 1.4 packed cell units/patient versus 0.8 +/- 1.0 packed cell units/patient; p = 0.0001). Patients with glucose-6-phosphate dehydrogenase deficiency who are undergoing cardiac surgery may have a more complicated course with a longer ventilation time, more hypoxia, increased hemolysis, and a need for more blood transfusion. Because this difference may be caused by subnormal free radical deactivation, strategies that minimize bypass in general and free radicals specifically may be beneficial.


Regional Differences Between Perisynovial and Infrapatellar Adipose Tissue Depots and Their Response to Class II and Class III Obesity in Patients With Osteoarthritis.
Obesity is associated with an increased risk of developing osteoarthritis (OA), which is postulated to be secondary to adipose tissue-dependent inflammation. Periarticular adipose tissue depots are present in synovial joints, but the association of this tissue with OA has not been extensively explored. The aim of this study was to investigate differences in local adipose tissue depots in knees with OA and characterize the changes related to class II and class III obesity in patients with end-stage knee OA. Synovium and the infrapatellar fat pad (IPFP) were collected during total knee replacement from 69 patients with end-stage OA. Histologic changes, changes in gene and protein expression of adiponectin, peroxisome proliferator-activated receptor γ (PPARγ), and Toll-like receptor 4 (TLR-4), and immune cell infiltration into the adipose tissue were investigated. IPFP and synovium adipose tissue depots differed significantly and were influenced by the patient's body mass index. Compared to adipocytes from the IPFP and synovium of lean patients, adipocytes from the IPFP of obese patients were significantly larger and the synovium of obese patients displayed marked fibrosis, increased macrophage infiltration, and higher levels of TLR4 gene expression. The adipose-related markers PPARγ in the IPFP and adiponectin and PPARγ in the synovium were expressed at lower levels in obese patients compared to lean patients. Furthermore, there were increased numbers of CD45+ hematopoietic cells, CD45+CD14+ total macrophages, and CD14+CD206+ M2-type macrophages in both the IPFP and synovial tissue of obese patients. These differences suggest that IPFP and synovium may contain 2 different white adipose tissue depots and support the theory of inflammation-induced OA in patients with class II or III obesity. These findings warrant further investigation as a potentially reversible, or at least suppressible, cause of OA in obese patients.


Amplification of EVI1 on cytogenetically cryptic double minutes as new mechanism for increased expression of EVI1.
In acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), increased expression of EVI1 (ecotropic virus integration site 1) was found to be associated with adverse prognosis. Although increased expression of the EVI1 gene is mainly caused by chromosomal rearrangements involving chromosome band 3q26, where EVI1 is located, it can also be identified in cases without these rearrangements. The mechanisms that cause increased EVI1 expression in the absence of 3q26 rearrangements remain unclear. Here, we present four cases with increased EVI1 expression due to EVI1 amplification on cytogenetically cryptic double minutes (dmin). The dmin are small acentric chromosome structures and were observed in about 1% of AML and MDS. We investigated the four cases by conventional cytogenetics, fluorescence in situ hybridization, and array comparative genomic hybridization. Furthermore, EVI1 expression was measured by quantitative reverse transcriptase-PCR. By conventional chromosome analysis, the EVI1 dmin cannot be detected, due to the small size of the amplicons of 0.49-0.78 Mbp. Median % EVI1/ABL expression was 88.9% and therefore comparable to the median % EVI1/ABL expression of patients with EVI1 rearrangements. In conclusion, EVI1 amplification on cytogenetically cryptic dmin causes increased expression of EVI1 and is a new mechanism that causes increased EVI1 expression without a 3q26 rearrangement.


Materiality, Agency and Evolution of Lithic Technology: an Integrated Perspective for Palaeolithic Archaeology.
Considerations of materiality and object-oriented approaches have greatly influenced the development of archaeological theory in recent years. Yet, Palaeolithic archaeology has been slow in incorporating this emerging body of scholarship and exploring its bearing on the human deep past. This paper probes into the potential of materiality theory to clarify the material dynamics of the Plio-Pleistocene and seeks to re-articulate the debate on the evolution of our species with materiality discourses in archaeology and the humanities more broadly. We argue that the signature temporalities and geospatial scales of observation provided by the Palaeolithic record offer unique opportunities to examine the active role of material things, objects, artefacts and technologies in the emergence, stabilisation and transformation of hominin lifeworlds and the accretion of long-term trajectories of material culture change. We map three axes of human-thing relations-ecological, technical and evolutionary-and deploy a range of case studies from the literature to show that a critical re-assessment of material agency not only discloses novel insights and questions, but can also refine what we already know about the human deep past. Our exploration underscores the benefits of de-centring human behaviour and intentionality and demonstrates that materiality lends itself as a productive nexus of exchange and mutual inspiration for diverging schools and research interests in Palaeolithic archaeology. An integrated object-oriented perspective calls attention to the human condition as a product of millennial-scale human-thing co-adaptation, in the course of which hominins, artefacts and technologies continuously influenced and co-created each other.


Pineal N-acetyltransferase depression in rats exposed to heat.
Exposure of adult male rats to increased temperature of 33 +/- 1 degrees C for 3 and 10 days brought about decreases in pineal N-acetyltransferase activity. These and previous findings of pineal HIOMT inhibition under similar conditions support the postulation of a possible thermoregulatory role for the pineal gland.


In vitro and in vivo pharmacological characterisation of the potent and selective vasopressin V(1A) receptor antagonist 4-[4-(4-Chloro-phenyl)-5-[1,2,3]triazol-2-ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl-(3,5-difluoro-phenyl) methanone (PF-00738245).
The dysregulation of arginine vasopressin (AVP) release and activation of vasopressin receptors plays an important role in disease conditions including polycystic kidney disease, congestive heart failure and dysmenorrhoea. The development of potent and selective vasopressin receptor ligands is needed to help dissect the function of the specific subtypes in disease pathogenesis. Here we report the pharmacological characterisation of PF-00738245 in in vitro binding and functional assays using cells expressing vasopressin V(₁A), V(₁B) or V₂ receptors. PF-00738245 inhibited AVP binding to the recombinant human vasopressin V(₁A) receptor (K(i)=2.85 nM) and blocked AVP-induced rat aortic ring and human myometrial contraction (pK(B)=7.35 and 8.62 respectively). PF-00738245 was selective for the vasopressin V(1A) receptor by demonstrating minimal binding to vasopressin V(₁B) (3.6% inhibition at 10 μM) or functional activity at vasopressin V₂ receptors (8.1% agonist and -8.4% antagonist activity at 10 μM) as well as the oxytocin receptor (46.3% antagonist activity at 10 μM). The in vivo pharmacological properties were tested orally in the rat and PF-00738245 dose dependently blocked the effect of AVP on a capsaicin-induced cutaneous flare response. Taken together the data support the use of PF-00738245 as a potent and selective vasopressin V(₁A) receptor antagonist which may have utility in the treatment of disease conditions which are propagated by elevation in vasopressin V(₁A) receptor signalling.


Human papilloma virus infection and miscarriage: is there an association?
Human papilloma virus (HPV) infection is the most common viral infection of the reproductive tract. HPV infection is more prevalent in pregnant than in age-matched non-pregnant women and its prevalence increases as pregnancy progresses. A number of reports evaluated the role of HPV infection in miscarriages. In the present review, we summarize the existing evidence regarding the association between HPV infection and miscarriage. It is still unclear whether HPV infection is associated with increased risk for miscarriage. Studies in the field yielded conflicting findings and their conclusions are limited by a small sample size and/or methodological limitations. On the other hand, preclinical data support a role of HPV infection in placental dysfunction. Given the high prevalence of HPV infection and the possibility that vaccination against HPV might protect against miscarriage, more studies are needed to elucidate whether this common infection is associated with increased risk for miscarriage.


Study of genetic stability of human bone marrow multipotent mesenchymal stromal cells.
Immunophenotype, proliferation rate, and genetic stability parameters of bone marrow multipotent mesenchymal stromal cells were studied. Despite the reduction of proliferative activity by passages 11-12, the cells retained the characteristic immunophenotype. The incidence of spontaneous aneuploidy for autosomes 6, 8, 11 and sex chromosomes was evaluated. Two cultures of mesenchymal stromal cells carrying aneuploid cell clones were detected: with chromosome 8 trisomy and X chromosome monosomy. The results indicate the possibility of genetic transformation and selection of mesenchymal stromal cells with abnormal karyotype during in vitro culturing.


Celastrol and Rhynchophylline in the mitigation of simulated muscle atrophy under in vitro.
Muscular atrophy (MA) is a disease of various origins, i.e., genetic or the most common, caused by mechanical injury. So far, there is no universal therapeutic model because this disease is often progressive with numerous manifested symptoms. Moreover, there is no safe and low-risk therapy dedicated to muscle atrophy. For this reason, our research focuses on finding an alternative method using natural compounds to treat MA. This study proposes implementing natural substances such as celastrol and Rhynchophylline on the cellular level, using a simulated and controlled atrophy process. Methods: Celastrol and Rhynchophylline were used as natural compounds against simulated atrophy in C2C12 cells. Skeletal muscle C2C12 cells were stimulated for the differentiation process. Atrophic conditions were obtained by the exposure to the low concertation of doxorubicin and validated by FoxO3 and MAFbx. The protective and regenerative effect of drugs on cell proliferation was determined by the MTT assay and MT-CO1, VDAC1, and prohibitin expression. Results: The obtained results revealed that both natural substances reduced atrophic symptoms. Rhynchophylline and celastrol attenuated atrophic cells in the viability studies, morphology analysis by diameter measurements, modulated prohibitin VDAC, and MT-CO1 expression. Conclusions: The obtained results revealed that celastrol and Rhynchophylline could be effectively used as a supportive treatment in atrophy-related disorders. Thus, natural drugs seem promising for muscle regeneration.


Physical connections between different SSVEP neural networks.
This work investigates the mechanism of the Steady-State Visual Evoked Potential (SSVEP). One theory suggests that different SSVEP neural networks exist whose strongest response are located in different frequency bands. This theory is based on the fact that there are similar SSVEP frequency-amplitude response curves in these bands. Previous studies that employed simultaneous stimuli of different frequencies illustrated that the distribution of these networks were similar, but did not discuss the physical connection between them. By comparing the SSVEP power and distribution under a single-eye stimulus and a simultaneous, dual-eye stimulus, this work demonstrates that the distributions of different SSVEP neural networks are similar to each other and that there should be physical overlapping between them. According to the band-pass filter theory in a signal transferring channel, which we propose in this work for the first time, there are different amounts of neurons that are involved under repetitive stimuli of different frequencies and that the response intensity of each neuron is similar to each other so that the total response (i.e., the SSVEP) that is observed from the scalp is different.


Encoding mu-opioid receptor biased agonism with interaction fingerprints.
Opioids are potent painkillers, however, their therapeutic use requires close medical monitoring to diminish the risk of severe adverse effects. The G-protein biased agonists of the μ-opioid receptor (MOR) have shown safer therapeutic profiles than non-biased ligands. In this work, we performed extensive all-atom molecular dynamics simulations of two markedly biased ligands and a balanced reference molecule. From those simulations, we identified a protein-ligand interaction fingerprint that characterizes biased ligands. Then, we built and virtually screened a database containing 68,740 ligands with proven or potential GPCR agonistic activity. Exemplary molecules that fulfill the interacting pattern for biased agonism are showcased, illustrating the usefulness of this work for the search of biased MOR ligands and how this contributes to the understanding of MOR biased signaling.


Experimental investigation of the effect of stiffness, exposure time and scan direction on the dimension of ultrasound histotripsy lesions.
Histotripsy uses high-intensity focused ultrasound to create energetic bubble clouds inside tissue to liquefy a region and has the advantages of higher contrast B-mode monitoring and sharp borders. This study experimentally investigated the effects of stiffness, exposure time and scan direction on the size of histotripsy-induced lesions in agar samples. A targeted region 0.45 cm wide (lateral) and 0.6 cm deep (axial) was scanned with the step sizes of 0.075 cm and 0.3 cm, respectively. The single-element spherically focused source (1.1 MHz, 6.34 cm focal length, f/1) had the peak compressional and rarefactional pressures of approximately 102 and 17 MPa. Pulses consisted of 20-cycle sine wave tone bursts with a burst period of 3 ms and exposure time of 15, 30 or 60 s. Also, both inward and outward scan direction were tested along the beam axis. The liquefied lesions generally had a larger size than the initially targeted region with larger sizes corresponding to softer agar and longer exposure. There was not a statistically significant difference in the lesion size with scan direction.


Expanding the targeting scope of FokI-dCas nuclease systems with SpRY and Mb2Cas12a.
CRISPR-Cas9 and Cas12a are widely used sequence-specific nucleases (SSNs) for genome editing. The nuclease domains of Cas proteins can induce DNA double strand breaks upon RNA guided DNA targeting. Zinc finger nucleases (ZFNs) and Transcription Activator-Like Effector Nucleases (TALENs) have been popular SSNs prior to CRISPR. Both ZFNs and TALENs are based on reconstitution of two monomers with each consisting of a DNA binding domain and a FokI nuclease domain. Inspired by the configuration of ZFNs and TALENs, dimeric FokI-dCas9 systems were previously demonstrated in human cells. Such configuration, based on a pair of guide RNAs (gRNAs), offers great improvement on targeting specificity. To expand the targeting scope of dimeric FokI-dCas systems, the PAM (protospacer adjacent motif)-less SpRY Cas9 variant and the PAM-relaxed Mb2Cas12a system were explored. Rice cells showed that FokI-dSpRY had more robust editing efficiency than a paired SpRY nickase system. Furthermore, a dimeric FokI-dMb2Cas12a system was developed that displayed comparable editing activity to Mb2Cas12a nuclease in rice cells. Finally, a single-chain FokI-FokI-dMb2Cas12a system was developed that cuts DNA outside its targeting sequence, which could be useful for many versatile applications. Together, this work greatly expanded the FokI based CRISPR-Cas systems for genome editing.


Optical nonlinearities in high-confinement silicon carbide waveguides.
We demonstrate strong nonlinearities of n2=8.6±1.1×10(-15) cm2 W(-1) in single-crystal silicon carbide (SiC) at a wavelength of 2360 nm. We use a high-confinement SiC waveguide fabricated based on a high-temperature smart-cut process.


Detection of impending pericardial tamponade during skeletal imaging.
Bone imaging using Tc-99m MDP was performed on a 68-year-old man with a newly diagnosed adenocarcinoma of the lung. The image unexpectedly showed increased activity in the heart area. Emergent echocardiography demonstrated impending pericardial tamponade. A malignant pericardial effusion was verified by pericardiocentesis.


Stereoselective synthesis of (2S,3S,4R,5S)-3,4-dihydroxy-2,5-dihydroxymethyl pyrrolidine from L-sorbose.
One of the most frequently synthesized iminosugar derivatives is DMDP. Starting from L-sorbose, a practical method for the synthesis of derivatives of this five-membered iminocyclitol has been developed, involving straightforward steps and a convenient selective reduction of a ketoxime intermediate.


Prevalence of Thalassemia among Newborns: A Re-visited after 20 Years of a Prevention and Control Program in Northeast Thailand.
To provide accurate prevalence information of thalassemia in northeast Thailand, authors performed thalassemia screening in newborns after 20 years implementation of a prevention and control program. Study was done on 350 cord blood specimens collected consecutively at Maternal and Child Hospital, Regional Health Promotion Center 7, Khon Kaen, Thailand. All kinds of α- and β-thalassemias were identified using combined hemoglobin (Hb) and DNA analyses. Among 350 newborns examined, subjects with thalassemia genes were identified in 184 (52.6%) cases with as many as 22 different genotypes. The most prevalent one was Hb E (39.1%). The incidence of 3.1% α0-thalassemia, 25.9% α+-thalassemia, 5.4% Hb Constant Spring and 1.4% of Hb Paksé were encountered. Heterozygous β-thalassemia was found in 2 cases (0.6%). Hb capillary electrophoresis could demonstrate Hb E in all cases with Hb E and detected different levels of Hb Bart's for different α-thalassemia genotypes but not in all cases with α-thalassemia. No newborn with severe thalassemia diseases was encountered. This study reveals that α-thalassemia, β-thalassemia, and Hb E carriers as well as complex thalassemia syndromes are still prevalence and indicates a need for continuing a prevention and control program in the region.


Dynamic plasticity and failure of high-purity alumina under shock loading.
Most high-performance ceramics subjected to shock loading can withstand high failure strength and exhibit significant inelastic strain that cannot be achieved under conventional loading conditions. The transition point from elastic to inelastic response prior to failure during shock loading, known as the Hugoniot elastic limit (HEL), has been widely used as an important parameter in the characterization of the dynamic mechanical properties of ceramics. Nevertheless, the underlying micromechanisms that control HEL have been debated for many years. Here we show high-resolution electron microscopy of high-purity alumina, soft-recovered from shock-loading experiments. The change of deformation behaviour from dislocation activity in the vicinity of grain boundaries to deformation twinning has been observed as the impact pressures increase from below, to above HEL. The evolution of deformation modes leads to the conversion of material failure from an intergranular mode to transgranular cleavage, in which twinning interfaces serve as the preferred cleavage planes.


Optimization and characterization of polysaccharide-based bioflocculant produced by Paenibacillus elgii B69 and its application in wastewater treatment.
The optimization, purification and characterization of bioflocculant produced by Paenibacillus elgii B69 were investigated. The bioflocculant was an exopolysaccharide composed of glucose, glucuronic acid, mannose and xylose. The maximum bioflocculant production was about 25.63 g/L achieved with sucrose at 51.35 g/L, peptone at 6.78 g/L and yeast extract at 0.47 g/L optimized by response-surface methodology. In addition, a series of experiments was performed to investigate the flocculation activities towards kaolin clay, dyeing pigment, heavy metal ion, and real wastewater and the result indicated the new bioflocculant had high activities towards all the tested pollutions. These results showed its great potential for water pretreatment used in industry.


A critical analysis of intraoperative time utilization in laparoscopic adrenalectomy.
Time and efficiency analysis is a technique common in industry that is being applied to surgical procedures. The aim of this study is to analyze the time spent performing the component parts of laparoscopic adrenalectomy by both the lateral transabdominal and the posterior retroperitoneal approaches. Operational videotapes of 33 patients undergoing laparoscopic adrenalectomy (12 lateral, 21 posterior) were reviewed. The operation was divided into six steps: trocar entry, laparoscopic ultrasonography, exposure of the adrenal gland, dissection of the adrenal, extraction of specimen, and irrigation-aspiration. Time spent for each step and the relation with age, gender, body mass index (BMI), tumor size, side, and histology were assessed using Student's t-test, Pearson correlation, and regression analysis. Although tumor size was larger in the lateral compared to the posterior approach (5.5 vs 2.5 cm, p < 0.001), there was no difference between the groups regarding total operating time (116.1 vs 112.8 min). Most of the operating time was spent on dissection of the adrenal gland with both techniques (lateral, 60%; posterior, 66%). Exposure of the adrenal gland was longer in the lateral compared to the posterior approach (15.1 vs 5.8 min, respectively; p < 0.05). In the transabdominal technique, this step was longer on the right side than on the left (18.9 vs 11.4 min, respectively; p < 0.05). In the lateral approach, dissection time was dependent on tumor size (r = 0.90, p < 0.05) but not on BMI, whereas in the posterior approach both tumor size and BMI were positively correlated (r = 0.56 and r = 0.64, respectively). To our knowledge, this is the first study to apply time analysis techniques to laparoscopic adrenal surgery. Understanding the variables that affect operative time may influence the choice of the surgical approach in a given patient. This study also suggests that efforts to improve operative efficiency are best directed at the dissection of the adrenal.


Comprehensive study of mesoporous carbon functionalized with carboxylate groups and magnetic nanoparticles as a promising adsorbent.
Highly ordered mesoporous carbon functionalized with carboxylate groups and magnetic nanoparticles has been successfully synthesized. By oxidative treatment using (NH(4))(2)S(2)O(8) and H(2)SO(4) mixed solution, numerous hydrophilic groups were created in the mesopores without destroying the ordered mesostructure of CMK-3. Through the in situ reduction in Fe(3+), magnetic nanoparticles were successfully introduced into the mesopores, resulting in the multifunctional mesoporous carbon Fe-CMK-3. The obtained hybrid carbon material possesses ordered mesostructure, high Brunauer-Emmett-Teller (BET) surface area up to 1013 m(2)/g, large pore volume of about 1.16 cm(3)/g, carboxylic surface, and excellent magnetic property. When used as an adsorbent, Fe-CMK-3 exhibits excellent performances for removing toxic organic compounds from waster-water, with a high adsorption capacity, an extremely rapid adsorption rate, and an easy magnetically separable process. In the case of requiring emergency removal of large amount of organic pollutants in aqueous, the hybrid carbon adsorbent would be an ideal choice.


Development of cellular signaling pathway inhibitors as new antivirals against influenza.
Influenza virus exploits a number of cellular signaling pathways during the course of its replication, rendering them potential targets for new therapeutic interventions. Several preclinical approaches are now focusing on cellular factors or pathways as a means of treating influenza. By targeting host factors, rather than viral mechanisms, these novel therapies may be effective against multiple virus strains and subtypes, and are less likely to elicit viral drug resistance. The most promising candidates are inhibitors of intracellular signaling cascades that are essential for virus replication. This article reviews novel approaches and compounds that target the Raf/MEK/ERK signaling pathway, NF-κB signaling, the PI3K/Akt pathway and the PKC signaling cascade. Although these new antiviral strategies are still in an early phase of preclinical development, results to date suggest they offer a new approach to the treatment of influenza, supplementing direct-acting antiviral drugs.


Monoclonal antibody 2C5: a marker for a subpopulation of small neurones in rat dorsal root ganglia.
Monoclonal antibody 2C5 labels a subset of dorsal root ganglion neurones in the rat. The cell sizes of these neurones fall within the range for the small dark cell population and the antibody labels between a half and two-thirds of the neurones in this size range. A subpopulation of small neurones was also labelled in the trigeminal and vagal ganglia. Other sites of immunoreactivity in the central nervous system are the region of the substantia gelatinosa of the spinal cord, fibres in Lissauer's tract, the tractus solitarius and the tuberculum olfactorium. These sites are consistent with the antigen being expressed by the central processes of primary afferent neurones. It is suggested that the size distributions of 2C5-positive dorsal root ganglion neurones and the pattern of 2C5 immunoreactivity within the spinal cord indicate that the labelled cells may be neurones with peripheral C fibers. Outside the nervous system the antigen is expressed in a number of specific cell types within a variety of organs. These include some pancreatic acinar cells, parietal cells of the gastric mucosa, some cells in taste buds, Leydig cells of the testis, scattered cells in lymph nodes and lung alveoli, some renal tubules, the epithelial lining of the fallopian tube, the epithelium covering the ovary and certain cells in the basal layer of the epidermis.


Time- and dose-dependent effects of protein kinase C on proximal bicarbonate transport.
Activation of protein kinase C has been shown to cause both stimulation and inhibition of transport processes in the brush-border membrane and renal tubule. This study was designed to examine the dose-response nature and time-dependent effect of 4 beta-phorbol-12-myristate-13-acetate (PMA) on the rates of bicarbonate absorption (JHCO3) and fluid absorption (Jv) in the proximal convoluted tubule (PCT) of rat kidney. Bicarbonate flux was determined by total CO2 changes between the collected fluid and the original perfusate as analyzed by microcalorimetry. Luminal perfusion of PMA (10(-10) approximately 10(-5) M) within 10 min caused a significant increase of JHCO3 and Jv. A peaked curve of the dose response was observed with maximal effect at 10(-8) M PMA on both bicarbonate and fluid reabsorption, which could be blocked completely by amiloride (10(3) M) and EIPA (10(-5) M). On the other hand, with an increase of perfusion time beyond 15 min. PMA (10(-8) and 10(-6) M) could inhibit JHCO3 and Jv. Amiloride (10(-3) M) or EIPA (10(-5) M) significantly inhibits JHCO3 and Jv, while there is no additive effect of PMA and amiloride or EIPA on PCT transport. An inactive phorbol-ester, 4 alpha-phorbol, that does not activate protein kinase C, had no effects on JHCO3 and Jv. Capillary perfusion of PMA (10(-8) M) significantly stimulate both JHCO3 and Jv; however, PMA did not affect glucose transport from either the luminal side or basolateral side of the PCT. These results indicate that activation of endogenous protein kinase C by PMA could either stimulate or inhibit both bicarbonate and fluid reabsorption in the PCT dependent on time and dose, and these effects are through the modulation of Na+/H+ exchange mechanism.


Dual emission fluorescent silver nanoclusters for sensitive detection of the biological coenzyme NAD+/NADH.
Fluorescent silver nanoclusters (Ag NCs) displaying dual-excitation and dual-emission properties have been developed for the specific detection of NAD(+) (nicotinamide adenine dinucleotide, oxidized form). With the increase of NAD(+) concentrations, the longer wavelength emission (with the peak at 550 nm) was gradually quenched due to the strong interactions between the NAD(+) and Ag NCs, whereas the shorter wavelength emission (peaking at 395 nm) was linearly enhanced. More important, the dual-emission intensity ratio (I395/I550), fitting by a single-exponential decay function, can efficiently detect various NAD(+) levels from 100 to 4000 μM, as well as label NAD(+)/NADH (reduced form of NAD) ratios in the range of 1-50.


Effects of air blower and pump failures on the performance of A2O processes for wastewater treatment.
The unexpected failure of equipment such as pumps and fans in wastewater treatment plants can reduce wastewater treatment efficiency, leading to direct leakage of untreated wastewater into the environment. It is hence important to predict the possible consequences of equipment failure to minimize the leakage of harmful substances. This study examines the impacts of equipment shutdown on the performance and recovery time of a laboratory-scale anaerobic/anoxic/aerobic system with regard to reactor conditions and water quality. Two days after the air blowers are stopped, the concentrations of the soluble chemical oxygen demand, NH4-N, and PO4-P in the effluent of the settling tank increase to 122 mg/L, 23.8 mg/L, and 46.6 mg/L, respectively. These concentrations return to their initial values after 12, 24, and 48 h of restarting the air blowers. The concentrations of PO4-P and NO3-N in the effluent increase to 58 mg/L and 20 mg/L, respectively, about 24 h after stopping the return activated sludge and mixed liquor recirculation pumps, owing to the release of phosphates in the settling tank and inhibition of denitrification.


Quantifying the contribution of long-range Saharan dust transport on particulate matter concentrations in Houston, Texas, using detailed elemental analysis.
The trans-Atlantic transport of North African dust by summertime trade winds occasionally increases ambient particulate matter (PM) concentrations in Texas above air quality standards. Exemptions from such exceedences can be sought for episodic events that are beyond regulatory control by providing qualitative supportive information such as satellite images and back-trajectories. Herein we demonstrate that chemical mass balancing can successfully isolate, differentiate, and quantify the relative contributions from local and global mineral dust sources through detailed measurements of a wide suite of elements in ambient PM. We identified a major dust storm originating in Northwest Africa in mid-July 2008 which eventually impacted air quality in Houston during July 25, 26, and 27, 2008. Daily PM2.5 and PM10 samples were collected at two sites in Houston over a 2-week period encompassing the Saharan dust episode to quantify the transported mineral dust concentrations during this peak event. Average PM concentrations more than doubled during the Saharan intrusion compared with non-Saharan. Relative concentrations of several elements often associated with anthropogenic sources were significantly diluted by crustal minerals coincident with the large-scale Saharan dust intrusion. During non-Saharan days, local mineral dust sources including cement manufacturing and soil and road dust contributed in total 26% to PM2.5 mass and 50% to PM10 mass; during the three-day Saharan episode the total dust contribution increased to 64% for PM2.5 and 85% for PM10. Importantly, this approach was also able to determine that local emissions of crustal minerals dominated the period immediately following the Saharan dust episode: simple quantification of bulk crustal materials may have misappropriated this elevated PM to trans-Atlantic transport of Saharan dust.


A new fat-dissociation method to detect lymph nodes in colorectal cancer: a prospective randomized study.
Histological examination of the lymph nodes (LNs) is crucial to determine the colorectal cancer (CRC) stage. We previously reported a new fat-dissociation method (FM) to detect LNs from surgically resected mesentery. This study aimed to examine the effectiveness of FM compared with that of conventional palpation method (PM) in CRC. This single-center, open-label, randomized controlled study was performed at Osaka International Cancer Institute in Japan in 2014. Randomization was performed using a computer-generated permuted-block sequence. Patients were stratified by surgical procedures and the LN dissection area. The primary endpoint was the time required for LN identification. The secondary endpoint was the number of LNs and 5-year cancer-specific survival. The 130 enrolled patients were randomly assigned in a 1:1 ratio to the FM and the PM groups. LN identification times were 45 (range 15-80) and 15 (range 7-30) minutes in the PM and the FM groups, respectively (P < 0.001). In the PM group, body mass index and identification time were correlated (P = 0.047). The number of LN which could be examined pathologically was 16 (range 2-48) and 18 (range 4-95) in the PM and FM groups, respectively (P = 0.546). In right-sided CRC, the number of LNs was higher in the FM group than in the PM group (P = 0.031). Relapse-free survival rates and cancer-specific survival rates did not differ between the groups. In conclusion, FM reduced the time required for LN detection without reducing the number of detected LNs, making it is a useful method to detect LNs in surgical specimens.


Highly sterically hindered olefins: a case of E- and Z-di-tert-butyl alpha,beta-unsaturated acids.
Use of a superbase in the Favorskii rearrangement of 12 resulted in the synthesis of highly sterically hindered olefins, (E)-2- tert-butyl-4,4-dimethyl-pent-2-enoic acid (4) and (Z)-2- tert-butyl-4,4-dimethyl-pent-2-enoic acid (3).


Effects of genistein aglycone in glucocorticoid induced osteoporosis: A randomized clinical trial in comparison with alendronate.
Glucocorticoid-induced osteoporosis (GIO) complicates the clinical management of patients subjected to long-term glucocorticoid use. This study explored the effects of genistein on bone loss in a randomized double-blind alendronate-controlled trial in postmenopausal women with GIO. 200 postmenopausal women (taking at least 5 mg of prednisone equivalents) since 3 months, or more, and expected to continue for at least other 12 months, were randomized to receive genistein (54 mg/day daily) or alendronate (70 mg once a week) for 24 months. Both groups received also Calcium and Vitamin D3 supplementation. Median bone mineral density (BMD) at the antero-posterior lumbar spine significantly increased from 0.75 g/cm2 at baseline to 0.77 g/cm2 at 1 year and 0.79 g/cm2 at 2 years in alendronate-treated patients and from 0.77 g/cm2 at baseline to 0.79 g/cm2 at 12 months and to 0.80 g/cm2 at 24 months in genistein recipients. No difference was observed between the two treatments. Median BMD at the femoral neck increased from 0.67 g/cm2 at baseline to 0.68 g/cm2 at 1 year and 0.69 g/cm2 at 2 years in alendronate-treated patients and from 0.68 g/cm2 at baseline to 0.70 g/cm2 at 12 months and to 0.71 g/cm2 at 24 months in genistein recipients. No difference was observed between alendronate and genistein groups in BMD. Regarding bone markers genistein and alendronate statistically decreased c-terminal telopeptide, while osteocalcin, bone-ALP, and sclerostin showed greater changes in genistein treated patients. This randomized clinical trial suggests that genistein aglycone represents an additional therapeutic option for patients with GIO.


Deforestation within breeding ranges may still drive population trends of migratory forest birds in the East Asian Flyway.
The East Asian Flyway (EAF) is the most species diverse of global flyways, with deforestation in its migratory landbird's non-breeding range suspected to be the main driver of population decline. Yet range-wide habitat loss impact assessments on EAF migratory landbirds are scarce, and seasonal variation in habitat preference of migratory species further increases the complexity for conservation strategies. In this study, we reviewed population trends of migratory forest breeding birds in the EAF along with their seasonal habitat preference from the literature and assessed the impact of forest cover change in species' breeding and non-breeding ranges on population trends. We found that 41.3% of the bird species with trend data available are declining, and most have higher forest preference in the breeding season. Despite 93.4% of the species experienced deforestation throughout their annual cycle, forest cover change in the non-breeding range was not identified as the main driver of population trend. However, forest cover change in species' regional breeding range interacts positively with the degree of breeding season forest preference in predicting population trends. We therefore stress that regional breeding habitat protection may still be important while following the call for cross-border collaboration to fill the information gap for flyway conservation.


Genetic parameters for carcass traits and body size in sheep for meat production.
The aim was to estimate the covariance components and genetic parameters of carcass traits and body size of meat sheep by employing animal models for single and multi-trait analyses. Data were collected from herds of adult Santa Ines sheep. The ribeye area, subcutaneous fat thickness, and rump fat thickness, evaluated in vivo by ultrasound images of the carcass; and morphometric traits: fat depth, rump height, chest circumference, chest depth, body length, and rump length were measured. The covariance components and genetic parameters for these traits were estimated by restricted maximum likelihood methodology, considering the random additive direct-genetic effects of the animal and errors associated with each observation, and the fixed effects of the contemporary group, the type of birth, and the age of the animal classes. Heritability estimates for carcass traits and animal size were higher in the three-trait analyses than in the single-trait analyses. The magnitudes of the values obtained indicate that genetic progress can be achieved by selection based on the traits studied.


The role of binocular neurons in the cat striate cortex in combining information from the two eyes.
Cats were raised under conditions of daily alternating monocular exposure, so that each eye received normal input, but the animals were never allowed to use both eyes simultaneously. With single cell recording techniques it could be shown that this led to a severe disturbance of the normal binocularity of cortical neurons. The cats were trained by operant techniques in a two-choice box to discriminate with each eye non-retinotopic stimulus pairs. To test the ability to combine binocular signals it was tested whether the learned discrimination would transfer to red/green colored stimuli which were viewed dichoptically through appropriately colored contract lenses. The arrangement was such that the positive stimulus could be distinguished from the negative stimuli only when the signals from both eyes were combined and used simultaneously. All cats showed immediate transfer, from the monocularly learned discrimination task to the dichoptic paradigm. This indicates that the presence of a normal population of binocular cortical cells in area 17 is not a prerequisite for the ability to use binocular cues for the solution of a pattern discrimination task.


Prothrombin complex concentrates utility for warfarin-associated hemorrhage.
Prothrombin Complex Concentrate (PCC) for reversal of warfarin is the main therapeutic option in cases of life-threatening bleeding. Aim of the study was to investigate for using 4-factor PCC brought to the therapeutic levels of International Normalized Ratio (INR) values in cases of life-threatening bleeding in Emergency Department. This retrospective cohort study was performed in a tertiary care university emergency department. Patients with active bleeding who were taking warfarin with INR levels of ≥1.5, and had received 4-factor prothrombin complex concentrate for treatment were included in to study. A total of 75 patients were included in the study. The median age of the study participants was 68 (minimum 23 to maximum 87) years and 45.3% (n = 34) of them were male. INR levels was normalized all patients who were received 4-factor PCC. Red blood cell (RBC) was transfused in 16 patients (21%) because of the low hemoglobin levels. Mean unite of the RBC packet was 2,75. The lengths of hospital stay of receiving 4-factor PCC rate were determined 4.9 ± 8.7 days. No thrombotic complications or adverse drug reactions were observed after 4-factor PCC administration in any of the patients. In our study 4-factor PCC was found to be effective and safe in rapidly reversing the effects of warfarin.


Characterization of the isozymes of bovine adrenal medullary phenylethanolamine N-methyltransferase.
Bovine adrenal medullary phenylethanolamine N-methyltransferase (EC 188.8.131.52) has been purified to apparent homogeneity. The enzymatically active monomer has a relative molecular weight of 30,000 and can be separated into at least four active charged isozymes. These isozymes, designated PNMT-1, PNMT-2, PNMT-3 and PNMT-4, have isoelectric points of 5.1, 5.2, 5.3 and 5.4, respectively. Kinetic parameters have been determined for each isozyme. The Kms for phenylethanolamine range from 11.9 to 45.9 microM; the Kms for S-adenosylmethionine range from 1.13 to 1.47 microM; and the Kis for the competitive inhibitor, S-adenosylhomocysteine, range from 0.12 to 0.22 microM. For isozymes PNMT-1 and PNMT-4, and Kms for S-adenosylhomocysteine are not significantly different. Vmax values for all of the isozymes do not change significantly in the presence of S-adenosylhomocysteine. Treatment of the purified isozymes with various endo- and exoglycosidases does not alter electrophoretic mobility. Hence, carbohydrate substitution must be minimal. No high mannan, complex sugars or terminal N-acetylglucosamine residues are present. The absence of carbohydrate is further supported by the inability of Schiff-periodic acid to stain the protein. Limited thermolysin digests of each isozyme show distinct peptide cleavage products. In conjunction with the kinetic and glycosylation data, this suggests that the isozymes of phenylethanolamine N-methyltransferase may be primary structural variants.


Computed tomography and ultrasound imaging of jumper's knee-patellar tendinitis.
We present nine cases of this relatively unreported condition affecting the patellar ligament in athletes. A comparison between ultrasound and computed tomography of this lesion, shows that whilst neither modality gives false positives, ultrasound is capable of greater distinction between the histological abnormalities confirmed at surgery.


African fictions to boost the scientific culture in Africa.
We popularize scientific topics through the 26-episode film series Science in the City, which depicts the perception of science in Africa. We campaign in African schools, universities and public events to initiate debates on science, inviting actors and scientists to engage with audiences.


Clinicopathological Characteristics and Incidence of Gastric Cancer in Eastern India: A Retrospective Study.
To study the association of gastric cancer with various clinicopathological traits in eastern India which can be used as an important factor for further analysis, understanding of the diseases and amelioration of patients. The retrospective study includes the patients who underwent subtotal or total gastrectomy from surgical oncology department of Chittaranjan National Cancer Institute (hospital) of West Bengal, India between 2014 and 2018. The study includes 751 gastric cancer patients from Chittaranjan National Cancer Institute. We used electronic hospital records to collect data on various clinical parameters and other information. We used Microsoft Office Excel 2007 spreadsheets for the statistical analyses. Incidence of gastric cancer is associated with mid age (40-59 years) group male patients and lymph node metastasis. Frequency of gastric cancer is highest in the antrum (42.21%). Of the mid age group gastric cancer patients, 35.02% were having much high risk of developing diffused type of adenocarcinoma (P < 0.00001). Tobacco intake in form of smoking was found as an important risk factor in gastric cancer development with risk ratio and odds ratio of 1.18 and 3.14 respectively. Collectively, the results of the present study confirm that incidence of diffused type of gastric cancer is increasing as an alarming rate in mid age group male patients and tobacco intake in the form of smoking as an independent risk factor for this type of cancer in eastern India. This result can be used to manage gastric carcinoma in future prospective clinical studies and in patient's improvement.


Doppler ultrasound diagnosis of brachial artery injury due to blunt trauma: A Case Report.
The brachial artery is the most common injured vessel in the upper extremity. Although vascular injury following blunt trauma is rare, it is a condition to be considered because it can easily be overlooked unless the clinician has a high suspicion. In this paper, we present a blunt trauma case with brachial arterial injury, upper extremity ischemia, and the need for urgent management to salvage the limb. A 28-year-old male had a right arm swelling, pain, and paleness accompanied by a weak pulse in the right radial artery and right-hand numbness. Following resuscitation, preoperative Doppler ultrasound revealed to the brachial artery injury. The right brachial artery had an occlusion with a thrombus. In spectral Doppler analysis, there were demonstrated parvus et tardus waveform in the distal arteries. Doppler ultrasound provided crucial information to make an accurate and rapid management decision.


Endocannabinoids: synthesis and degradation.
Endocannabinoids were defined in 1995 as endogenous agonists of cannabinoid receptors, i.e. of the G protein-coupled receptors for cannabis's psychoactive principle, Delta9-tetrahydrocannabinol. Although there appear to be several endocannabinoids, only two of such endogenous mediators have been thoroughly studied so far: anandamide and 2-arachidonoylglycerol (2-AG). A general strategy seems to apply to the biosynthesis and degradation of anandamide and 2-AG, although the levels of these two compounds appear to be regulated in different, and sometimes even opposing, ways. "Endocannabinoid enzymes", that is to say enzymes that catalyse endocannabinoid biosynthesis or degradation, have been identified and in some cases cloned, and will be described in this review together with their possible pharmacological targeting for therapeutic purposes. The cellular and subcellular localization and the modes for the regulation of the expression and activity of these enzymes play an important role in the functions played by the endocannabinoids under physiological and pathological conditions.


Editorial for the Special Issue on Physics in Micro/Nano Devices: From Fundamental to Application.
With the continuous miniaturization of micro/nano devices, it is of great importance to study the physics of these devices, both for fundamental and practical research [...].


Microsurgical ligation for incompletely coiled or recurrent intracranial aneurysms: a 17-year single-center experience.
In this retrospective single-center study, we presented our experience in the microsurgical management of incompletely coiled or recurrent aneurysms after initial endovascular coiling. During a 17-year period, 48 patients underwent microsurgical clipping of incompletely coiled or recurrent aneurysms after coiling (Gurian group B). The clinical data, surgical technique, and postoperative outcome were recorded and analyzed. Before coiling, 42 patients (87.5%) experienced aneurysm rupture. Most of the aneurysms (46/48, 96%) were located in the anterior circulation. After coiling, 6 patients had incompletely coiled aneurysms and 42 patients had recurrent aneurysms, with a mean time of 20.2 months from coiling to recurrence. Coil extrusion occurred in none of the incompletely coiled aneurysms and 71% (30/42) of the recurrent aneurysms. Clipping techniques are direct microsurgical clipping without coil removal in 16 patients, partial coil removal in 14 patients, and total coil removal in 18 patients. Postoperative and follow-up angiography revealed complete occlusion of the aneurysms in all patients. No patient died during postoperative follow-up period (mean, 78.9 months; range, 10-190 months). Good outcomes (GOS of 4 or 5) were achieved in 87.5% (42/48) of the patients at the final follow-up. Microsurgical clipping is effective for incompletely coiled or recurrent aneurysms after initial coiling. For recurrent aneurysms that have coils in the neck, have no adequate neck for clipping, or cause mass effects on surrounding structures, partial or total removal of coiled mass can facilitate surgical clipping and lead to successful obliteration of the aneurysms.


Spatiotemporal characteristics of form analysis in the human visual cortex revealed by rapid event-related fMRI adaptation.
The integration of local elements to coherent forms is at the core of understanding visual perception. Accumulating evidence suggests that both early retinotopic and higher occipitotemporal areas contribute to the integration of local elements to global forms. However, the spatiotemporal characteristics of form analysis in the human visual cortex remain largely unknown. The aim of this study was to investigate form analysis at different spatial (global vs. local structure) and temporal (different stimulus presentation rates) scales across stages of visual analysis (from V1 to the lateral occipital complex-LOC) in the human brain. We used closed contours rendered by Gabor elements and manipulated either the global contour structure or the orientation of the local Gabor elements. Our rapid event-related fMRI adaptation studies suggest that contour integration and form processing in early visual areas is transient and limited within the local neighborhood of their cells' receptive field. In contrast, higher visual areas appear to process the perceived global form in a more sustained manner. Finally, we demonstrate that these spatiotemporal properties of form processing in the visual cortex are modulated by attention. Attention to the global form maintains sustained processing in occipitotemporal areas, whereas attention to local elements enhances their integration in early visual areas. These findings provide novel neuroimaging evidence for form analysis at different spatiotemporal scales across human visual areas and validate the use of rapid event-related fMRI adaptation for investigating processing across stages of visual analysis in the human brain.


Evaluation of trueness in a denture base fabricated by using CAD-CAM systems and adaptation to the socketed surface of denture base: An in vitro study.
Computer-aided design and computer-aided manufacturing (CAD-CAM) systems are increasingly used to fabricate removable complete dentures. However, comparisons and analyses of the trueness and adaptation of the socketed surface of denture bases produced by milling (MIL) and digital light processing (DLP) are lacking. The purpose of this in vitro study was to evaluate and compare the trueness and socketed surface adaptation of denture bases fabricated by using additive and subtractive manufacturing. Based on a denture base standard tessellation language (STL) file, a total of 15 denture bases were produced by using DLP (horizontal and vertical direction) and MIL. The intaglio and cameo surfaces of the fabricated denture bases were scanned with a dental scanner. The scanned intaglio and cameo surfaces were overlapped with the corresponding reference denture base STL file for trueness evaluation. In addition, the ridge lap STL file of the diagnostic tooth arrangement, in which reverse normal was performed, was superimposed on the socketed surface of the denture base of all groups to evaluate adaptation. The root mean square (RMS) values of trueness and adaptation showed statistically significant differences (P<.05). For the trueness RMS value of the intaglio surface of the denture base, the MIL-denture base (MDB) group had the lowest value of 150 ±6 μm, whereas the vertical denture base (VDB) of the DLP group was the largest with 328 ±4 μm. For the trueness RMS value of the cameo surface, the MDB group was the lowest with 50 ±1 μm, whereas the VDB group was the largest with 334 ±24 μm. For the adaptation RMS value of the socketed surface of the denture base, the MDB group was the lowest with 44 μm, whereas the VDB group was the largest with 117 ±2 μm. Within the limits of this in vitro study, the MDB group showed better trueness and socketed surface adaptation than the DLP groups (HDB and VDB).


Munc18-1 domain-1 controls vesicle docking and secretion by interacting with syntaxin-1 and chaperoning it to the plasma membrane.
Munc18-1 plays pleiotropic roles in neurosecretion by acting as 1) a molecular chaperone of syntaxin-1, 2) a mediator of dense-core vesicle docking, and 3) a priming factor for soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated membrane fusion. However, how these functions are executed and whether they are correlated remains unclear. Here we analyzed the role of the domain-1 cleft of Munc18-1 by measuring the abilities of various mutants (D34N, D34N/M38V, K46E, E59K, K46E/E59K, K63E, and E66A) to bind and chaperone syntaxin-1 and to restore the docking and secretion of dense-core vesicles in Munc18-1/-2 double-knockdown cells. We identified striking correlations between the abilities of these mutants to bind and chaperone syntaxin-1 with their ability to restore vesicle docking and secretion. These results suggest that the domain-1 cleft of Munc18-1 is essential for binding to syntaxin-1 and thereby critical for its chaperoning, docking, and secretory functions. Our results demonstrate that the effect of the alleged priming mutants (E59K, D34N/M38V) on exocytosis can largely be explained by their reduced syntaxin-1-chaperoning functions. Finally, our data suggest that the intracellular expression and distribution of syntaxin-1 determines the level of dense-core vesicle docking.


Lifespan Control by Redox-Dependent Recruitment of Chaperones to Misfolded Proteins.
Caloric restriction (CR) extends the lifespan of flies, worms, and yeast by counteracting age-related oxidation of H2O2-scavenging peroxiredoxins (Prxs). Here, we show that increased dosage of the major cytosolic Prx in yeast, Tsa1, extends lifespan in an Hsp70 chaperone-dependent and CR-independent manner without increasing H2O2 scavenging or genome stability. We found that Tsa1 and Hsp70 physically interact and that hyperoxidation of Tsa1 by H2O2 is required for the recruitment of the Hsp70 chaperones and the Hsp104 disaggregase to misfolded and aggregated proteins during aging, but not heat stress. Tsa1 counteracted the accumulation of ubiquitinated aggregates during aging and the reduction of hyperoxidized Tsa1 by sulfiredoxin facilitated clearance of H2O2-generated aggregates. The data reveal a conceptually new role for H2O2 signaling in proteostasis and lifespan control and shed new light on the selective benefits endowed to eukaryotic peroxiredoxins by their reversible hyperoxidation.


Evaluation of markers of inflammation, insulin resistance and endothelial dysfunction in children at risk for overweight.
Childhood obesity is associated with impaired endothelial function, insulin resistance and inflammation. Being at risk for overweight has been defined as having a body mass index (BMI) between the 85th and 94th percentile for age and sex. In this study, we looked for features linked to cardiovascular risk in children who are at risk for overweight. Twenty-one children who were at risk for overweight (study group) and 20 children with a BMI between the 25th-74th percentiles (controls) were studied. Fasting blood levels of glucose, insulin, total cholesterol, HDL cholesterol, triglycerides, uric acid, fibrinogen and high sensitive C-reactive protein (CRP) were assessed in both groups. LDL-cholesterol, HOMA-IR and QUICKI indices were calculated. Flow-mediated Vasodilatation (FMD) was determined for the evaluation of endothelial function. Increased HOMA-IR was observed in children who were at risk for overweight. Waist circumference was the main predictor of insulin resistance in these children. Higher levels of CRP were found in the study group compared to controls, while plasma fibrinogen did not differ in the two groups. The children who were at risk for overweight had lower FMD values and slightly elevated lipids compared to controls; however, these differences were not statistically significant. Insulin resistance and inflammation indices were higher in children who were at risk for overweight as has been shown for obese children. The data suggest that appropriate treatment strategies for weight control are essential not only for obese children but also for those at risk for overweight.


Lesions of the midline thalamic nuclei impair classical conditioning under partial but not continuous reinforcement conditions.
Rabbits with lesions of the midline thalamic nuclei were compared to rabbits with sham lesions on classical eyeblink (EB) and heart rate (HR) conditioning. Separate groups of sham and lesioned animals received either 25, 50 or 100% reinforcement with a periorbital shock unconditioned stimulus. Animals with lesions showed slightly impaired EB conditioning, compared to sham animals, under the partial but not continuous reinforcement schedules. Midline lesions also reduced the magnitude of the decelerative HR conditioned response under partial but not continuous reinforcement conditions. These findings suggest that the midline thalamic nuclei, like the mediodorsal nucleus of the thalamus, process information required for response selection under non-optimal learning conditions.


Systematically increasing contextual interference is beneficial for learning sport skills.
To better understand the contextual interference effect, in two experiments we investigated a form of practice schedule that provided novices with systematic increases in contextual interference. This new type of practice schedule was compared with traditional blocked and random scheduling for two types of sports skills. In Experiment 1, we tested the hypothesis that practising variations of the same task with systematic increases in contextual interference would lead to superior performance compared with blocked or random scheduling. Participants practised golf putting tasks following a blocked, random or increasing schedule, which involved initial blocked trials, followed by serial practice trials, and ended with random scheduling. Participants who followed the increasing schedule had superior retention test performance. In Experiment 2, we tested if these learning benefits were observed when learning tasks controlled by different generalized motor programs. Participants practised three different basketball passes (chest, overhead, single arm) in a blocked, random or increasing schedule. Participants practising with gradual increases in contextual interference performed better on retention and transfer tests than participants practising with blocked or random scheduling. The results of these two expe


Preschool Depression: a Diagnostic Reality.
We review findings related to predictors, correlates, outcomes, and treatment of preschool depression that have been published in the last 3 years. Preschool depression displays a chronic course through late adolescence and is associated with temperamental and personality traits, poorer physical health, and negative parenting practices. Preschool depression predicts deficits into adolescence, including social difficulties and blunted neural response to rewards. Depressed preschoolers can experience suicidal ideation and behaviors and display an accurate understanding of the finality of death. A treatment for preschool depression has now been validated that uses the parent-child relationship to enhance emotion development and reduce depressive symptoms. Preschool depression is homotypic with depression that occurs later in life. Future work elucidating mechanisms through which preschool depression develops and informs the sub-groups for which particular treatments may be most effective will have considerable implications for prevention and early intervention.


Efficient augmentation of a long-lasting immune responses in HIV-1 gag DNA vaccination by IL-15 plasmid boosting.
Cytokines are major regulators of the immune response, and have been used as adjuvants to improve vaccine potency. In this study, we investigated the adjuvant effects of interleukin (IL)-15 on improving the immunogenicity of human immunodeficiency virus (HIV)-1 gag DNA vaccine in Balb/c mice. During a 370-day follow-up, cellular and humoral immune responses in three separate cohorts of mice were monitored. These results were exemplified through: lymphocyte proliferation, induction of antigen-specific CD8(+) T lymphocytes, long-term production of specific antibodies, and proportion of differentiated memory CD8(+) T cells. These data revealed that just boost of IL-15 at day 8 after co-immunization induced more homeostatic cell proliferation, augmented proliferation frequency of IFN-gamma-secreting antigen-specific CD8(+) T lymphocytes, maintained the long-lasting humoral immune response and promoted the turnover of memory T cell precursors into central memory T cells. Taken together, our data demonstrated that a single IL-15 boosting can enhance both the humoral and cellular immune responses of the HIV-1 gag DNA vaccination. This novel boosting strategy may facilitate the application of IL-15 as an adjuvant for HIV vaccination.


Vitamin D in adolescent idiopathic scoliosis: a meta-analysis.
The aim of this study was to compare serum vitamin D levels in girls with adolescent idiopathic scoliosis (AIS) and controls using meta-analysis methods. We searched Medline (via PubMed), Cochrane, Scopus, and Embase databases for studies evaluating outcomes in AIS, including patient age, body mass index, bone mineral density (BMD), and serum levels of parathyroid hormone (PTH), calcium, and phosphate, published between January 2000 and June 2020. We searched for studies that were limited to humans only. The inclusion criteria were a scoliosis study that measured vitamin D levels. We excluded duplicate publications such as review articles, case reports, and letters without original data. Two authors extracted data independently and resolved any discrepancies by consensus. Eight comparative studies were identified. Demographic characteristics, bone density, serum levels of vitamin D, parathyroid hormone, and phosphate levels were not significantly different between AIS group and controls, except for serum calcium levels. The serum calcium levels were lower in AIS group than in the controls. This review includes eight comparative studies reporting serum vitamin D and/or parathyroid hormone levels in AIS. Due to heterogeneity, a limited number of meta-analyses have shown a weak correlation between serum vitamin D levels and the incidence of AIS. Larger, multicenter studies are therefore needed to validate the results.


Patient-Centered Home Hemodialysis: Approaches and Prescription.
Writing a home hemodialysis (HD) prescription is a complex, multifactorial process that requires the incorporation of patient values, preferences, and lifestyle. Knowledge of the different options available for home HD modality (conventional, nocturnal, short daily, and alternate nightly) is also important when customizing a prescription. Finally, an understanding of the different home HD machines currently approved for use at home and their different attributes and limitations helps guide providers when formulating their prescriptions. In this review article, we set out to address these different aspects to help guide providers in providing a patient-centered home HD approach.


Light emitting diodes applied in Synechococcus nidulans cultures: Effect on growth, pigments production and lipid profiles.
Researches about light emitting diodes (LEDs) as energy source in microalgae cultivations has been growing in recent years due to its spectral quality, durability and reduced energy consumption. In this study, green, red and yellow LEDs were evaluated as energy source in Synechococcus nidulans LEB 115 cultures. Productivities and specific growth rates were up to 2.5 times greater than in cultures using fluorescent light. The different LED colors evaluated did not influence the chlorophyll, carotenoid or lipid productions. Biomass cultivated with LEDs showed high amounts of saturated fatty acids (above 48%), which is desirable for biodiesel production. In addition to the Synechococcus nidulans LEB 115 growth stimulation, the application of green, red and yellow LEDs in the cultivations produces potential biomass for biodiesel synthesis and other industrial interest biomolecules utilization.


Tacrolimus as rescue therapy for steroid-dependent/steroid-refractory ulcerative colitis: Experience from tertiary referral center in India.
Between 20% and 40% of patients with severe ulcerative colitis (UC) are either steroid-refractory UC (SRUC) or steroid-dependent UC (SDUC). Tacrolimus is an oral and relatively inexpensive drug, which has been extensively used in Japan for steroid-refractory and steroid-dependent disease. Patients diagnosed with SDUC/SRUC were treated with tacrolimus 0.05-0.1 mg/kg in this prospective study. Clinical Mayo score (CMS) and UC Endoscopic Index of Severity (UCEIS) were evaluated prior to starting the drug and subsequently after 8 weeks. 5-Aminosalicylic acid agents (5-ASA) and immunomodulators were continued if the patients were previously on these drugs. Clinical response at 8 weeks was defined as decrease in CMS by at least 3 points. Clinical remission was defined as CMS ≤2 and combined remission as CMS≤2 with UCEIS <3. Fifty-two patients (29 males) with a mean age of 35.1± 12.8 years with predominantly E3 disease (71%) were prospectively evaluated in this study. SDUC and SRUC were diagnosed in 31 and 21 patients, respectively. Seven failed treatment within 8 weeks, four were subjected to surgery, and 3 were switched to infliximab. Forty-two patients continued tacrolimus for 8 weeks. Mean CMS and UCEIS prior to starting tacrolimus were 6 ± 1.1 and 4.8 ± 1.1, respectively. At 8 weeks, median CMS and UCEIS decreased to 2.6 ± 1.7 and 2.7 ± 1.3, respectively. Clinical response was documented in 29 patients (56%) at week 8 whereas clinical remission was seen in 25 patients (48%). Combined clinical and endoscopic remissions were seen in 18 patients (35%). Except for a single patient who developed reversible renal dysfunction, no other adverse event was observed. Our results show that tacrolimus is effective in inducing a clinical response in 56% of patients with SDUC and SRUC. In view of its low cost and safety profile, it may be considered first-line therapy for SDUC/SRUC.


Supramolecular aggregates of cyclodextrins with co-solvent modulate drug dispersion and release behavior of poorly soluble corticosteroid from chitosan membranes.
In this study, the ability of different beta-cyclodextrins to facilitate homogeneous dispersion of triamcinolone acetonide (TA) into chitosan membranes is assessed. Drug loading was assessed through atomic force microscopy (AFM), scanning electron microscopy (MEV-FEG), and X-ray diffraction analyses. Drug interactions with the co-polymer were investigated with Fourier transform infrared spectroscopy, thermal analyses. Swelling assay, and in vitro drug release experiment were used to assess TA release behavior. Undispersed particles of drug were observed to remain in the simple chitosan membranes. Hydroxypropyl-β-cyclodextrin enabled the dispersion of TA into chitosan membranes and subsequent sustained drug release. In addition, the membrane performance as a drug delivery device is improved by adding specified amounts of the co-solvent triethanolamine. The experimental data presented in this study confirm the utility of our novel and alternative approach for obtaining a promising device for slow and controlled release of glucocorticoids, such as triamcinolone acetonide, for topical ulcerations.


Excretion of RNA catabolites by rats with hepatoma transplants.
Rats with transplants of Morris Hepatoma 5123 excreted in their urine greater than normal amounts of modified nucleosides and bases, catabolites of RNA. Despite rapid growth of the neoplasm, the elevated levels did not appear until 22 days after inoculation with the tumor. With tumor progression, there were increased levels and number of these catabolites. This study also suggests that the source of the elevated RNA catabolites is mainly from the host RNA rather than from tumor tissue and also that mRNA and rRNA as well as tRNA may contribute to the urinary levels.


ILKAP regulates ILK signaling and inhibits anchorage-independent growth.
ILKAP is a protein phosphatase 2C that selectively associates with integrin linked kinase, ILK, to modulate cell adhesion and growth factor signaling. We investigated the role of endogenous cellular ILKAP in antagonizing ILK signaling of two key targets, PKB and GSK3beta. Silencing of endogenous ILKAP by short interfering RNA (siRNA) stimulated GSK3beta phosphorylation at S9, with no effect on PKB S473 phosphorylation. In LNCaP prostate carcinoma cells, transient or stable expression of ILKAP suppressed ILK immune complex kinase activity, demonstrating an interaction between ILKAP and ILK. Consistent with the silencing data, ILKAP inhibition of ILK selectively inhibited S9 phosphorylation of GSK3beta without affecting S473 phosphorylation of PKB. The ILKAP-mediated inhibition of S9 phosphorylation was rescued by overexpression of ILK, but not by a dominant-negative ILK mutant. The expression level of cyclin D1, a target of ILK-GSK3beta signaling, was inversely correlated with ILKAP protein levels, suggesting that antagonism of ILK modulates cell cycle progression. ILKAP expression increased the proportion of LNCaP cells in G1, relative to vector control cells, and siRNA suppression of ILKAP increased entry of cells into the S phase, consistent with ILK antagonism. Anchorage-independent growth of LNCaP cells was inhibited by ILKAP, suggesting a critical role in the suppression of cellular transformation. Taken together, our results indicate that endogenous ILKAP activity inhibits the ILK-GSK3beta signaling axis, and suggest that ILKAP activity plays an important role in inhibiting oncogenic transformation.Oncogene (2004) 23, 3454-3461. doi:10.1038/sj.onc.1207473 Published online 1 March 2004


Reproductive and metabolic responses of desert adapted common spiny male mice (Acomys cahirinus) to vasopressin treatment.
Sufficient amounts of water and food are important cues for reproduction in an unpredictable environment. We previously demonstrated that increased osmolarity levels, or exogenous vasopressin (VP) treatment halt reproduction of desert adapted golden spiny mice Acomys russatus. In this research we studied gonad regulation by VP and food restriction (FR) in desert adapted common spiny mouse (A. cahirinus) males, kept under two different photoperiod regimes-short (SD-8L:16D) and long (LD-16L:8D) days. Mice were treated with VP, FR, and VP+FR for three weeks. Response was assessed from changes in relative testis mass, serum testosterone levels and mRNA receptor gene expression of VP, aldosterone and leptin in treated groups, compared with their controls. SD-acclimation increased testosterone levels, VP treatment decreased expression of aldosterone mRNA receptor in the testes of SD-acclimated males. FR under SD-conditions resulted in testosterone decrease and elevation of VP- receptor gene expression in testes. Aldosterone receptor mRNA expression was also detected in WAT. These results support the idea that water and food availability in the habitat may be used as signals for activating the reproductive system through direct effects of VP, aldosterone and leptin on the testes or through WAT by indirect effects.


The relation of nasality and nasalance to nasal port area based on a computational model.
The purpose of this study was to examine the relation of perceptual ratings of nasality by experienced listeners, measures of nasalance, and the size of the nasal port opening for three simulated English corner vowels, /i/, /u/, and /a/. Samples were generated using a computational model that allowed for exact control of nasal port size and a direct measure of nasalance. Perceptual ratings were obtained using a paired-stimulus presentation. Five experienced listeners. Measures of nasalance and perceptual nasality ratings. Differences in nasalance and perceptual ratings of nasality were noted among the three vowels, with values being greater for the high vowels /i/ and /u/ compared to the low vowel /a/. Listeners detected nasality for the high and low vowels simulated with nasal port areas of 0.01 and 0.15 cm(2), respectively. Correlations between ratings of nasality and nasalance were high for all three vowels. Results of the present study show a high correlation between ratings of nasality and measures of nasalance for nasal port areas ranging from 0 to 0.5 cm(2). The correlations were based on sustained vowel samples. The restricted speech sample limits generalization of the findings to clinical data; however, the results are a demonstration of the usefulness of modeling to understand the perceptual phenomena of nasality.


Synaptic Terminal Density Early in the Course of Schizophrenia: An In Vivo UCB-J Positron Emission Tomographic Imaging Study of Synaptic Vesicle Glycoprotein 2A.
The synaptic hypothesis is an influential theory of the pathoetiology of schizophrenia (SCZ), which is supported by the finding that there is lower uptake of the synaptic terminal density marker [11C]UCB-J in patients with chronic SCZ than in control participants. However, it is unclear whether these differences are present early in the illness. To address this, we investigated [11C]UCB-J volume of distribution (VT) in antipsychotic-naïve/free patients with SCZ who were recruited from first-episode services compared with healthy volunteers. Forty-two volunteers (SCZ n = 21, healthy volunteers n = 21) underwent [11C]UCB-J positron emission tomography to index [11C]UCB-J VT and distribution volume ratio in the anterior cingulate, frontal, and dorsolateral prefrontal cortices; the temporal, parietal and occipital lobes; and the hippocampus, thalamus, and amygdala. Symptom severity was assessed in the SCZ group using the Positive and Negative Syndrome Scale. We found no significant effects of group on [11C]UCB-J VT or distribution volume ratio in most regions of interest (effect sizes from d = 0.0-0.7, p > .05), with two exceptions: we found lower distribution volume ratio in the temporal lobe (d = 0.7, uncorrected p < .05) and lower VT/fp in the anterior cingulate cortex in patients (d = 0.7, uncorrected p < .05). The Positive and Negative Syndrome Scale total score was negatively associated with [11C]UCB-J VT in the hippocampus in the SCZ group (r = -0.48, p = .03). These findings indicate that large differences in synaptic terminal density are not present early in SCZ, although there may be more subtle effects. When taken together with previous evidence of lower [11C]UCB-J VT in patients with chronic illness, this may indicate synaptic density changes during the course of SCZ.