Suicide patterns in children and adolescents: a review from a pediatric institution in England.
Suicide is a catastrophic event to both families and communities yet it is potentially preventable. This study aims to determine incidence and patterns of suicide in children and young adolescents in our region, raise awareness of this entity as a potentially preventable cause of death in this age group, and identify its possible associated risk factors. We retrospectively reviewed suicide cases presenting as sudden unexpected death in children and adolescents that underwent coronial post-mortems at our institution. This is the largest pathological review of completed suicide in children and young adolescents within a single institution in the United Kingdom. We identified 23 suicide cases during a 12 year period from 2003 to 2015, in which 18 cases (78%) were male and 5 cases (22%) were female. The age range was from 8 to 16 years (mean age 12.82 +/- 2.52 SD). With the exception of one case, all of the victims were Caucasian. The majority, 19 cases (81%), were found dead inside their place of residence, 15 of whom were discovered in their own bedrooms. Twenty-one cases (91%) died from neck compression due to hanging; 6 cases (26%) had used the cord of a dressing gown and 5 (22%) opted to use a belt as the ligature. Two cases (9%) that died from multiple-drug toxicity were female. In 7 cases (30.5%) there was evidence of self-harm and in 3 cases (13%) there was a history of previous suicide attempts. Petechial hemorrhages were found at autopsy in more than half of hanging victims and only three cases (14%) displayed dual distribution of post-mortem hypostasis (back and legs). Seven victims (30.5%) left some form of suicide message to family members and friends, 2 of which wrote the message on their arm. Parental separation, conflict with parents, and depression, were common amongst decedents prior to committing suicide. Substance abuse was uncommon in suicide within our cases. Valuable information is available from thorough review of suicide data in children and young adolescents from a single institution. Pathologists and clinicians can play crucial roles in identifying potential risk factors that may contribute to prevent future deaths.


Biomarkers and Immunotherapeutic Targets in Glioblastoma.
Glioblastoma (GBM) is an aggressive central nervous system cancer with poor prognosis despite maximal therapy. The recent advent of immunotherapy holds great promise for improving GBM survival and has already made great strides toward changing management strategies. A diverse set of biomarkers have been implicated as immunotherapeutic targets and prognostic indicators in other cancers. Some of the more extensively studied examples include cytokines (IL-4, IL-13, and TGF-β), checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, CD137, GITR, OX40), and growth/angiogenesis proteins (endoglin and EGFR). Emerging theories involving the tumor mutational landscape and microbiome have also been explored in relation to cancer treatment. Although identification of novel biomarkers may improve and help direct treatment of patients with GBM, the next step is to explore the role of biomarkers in precision medicine and selection of specific immunotherapeutic drugs in an individualized manner.


A capillary electrophoretic assay for ribonuclease H activity.
A capillary electrophoretic assay was developed to measure the ribonuclease (RNase) H activity of human immunodeficiency virus (HIV) type 1 reverse transcriptase. Cleavage of a fluorescein-labeled RNA-DNA heteroduplex was monitored by capillary electrophoresis. This new assay was used as a secondary assay to confirm hits from a high-throughput screening program. Since autofluorescent compounds in samples migrated differently from both substrate and product in most cases, the assay was extremely robust for assaying enzymatic inhibition of such samples, in contrast to a simple well-based approach. The assay was broadly applicable to other RNases H, specifically those from human, Escherichia coli, and HIV-2, although product profiles varied for each enzyme.


Immune interferon modulation of in vitro murine anti-human T cell monoclonal antibody-mediated cytotoxicity.
Limited antitumor effects have been achieved in clinical trials with murine monoclonal antibody T101, perhaps because of its limited ability to effect complement-mediated or cell-mediated cytotoxicity. We explored the effects of recombinant immune interferon on T101-mediated cytotoxicity in vitro. Interferon failed to enhance expression of the antigen detected by T101 on target cells, but it did increase Fc receptor binding of T101 and other IgG2A and IgG3 murine proteins, but not IgG1 or IgG2B. Preincubation of U937, HL60, and human mononuclear cells with 100 U of immune interferon for 48 hr, while T101 was preincubated with various T cell line targets or human CLL cells at 4 degrees C for 30 min before combining effectors and targets for 4 hr at 37 degrees C, resulted in cytotoxicity of 18 to 44% of maximum. Cytotoxicity in the absence of interferon or T101 was less than 5%. Unfortunately, rapid modulation of antigen-antibody when T101 was preincubated with targets at 37 degrees C prevented any increase in cytotoxicity under those conditions. We conclude that immune interferon can augment T101-mediated cytotoxicity in vitro, but it is unlikely that it would enhance T101-mediated cytotoxicity via complement or cell-mediated mechanisms in vivo.


Theory of deep minima in (e,2e) measurements of triply differential cross sections.
Deep minima in He(e,2e)He+ triply differential cross sections are traced to vortices in atomic wave functions. Such vortices have been predicted earlier, but the present calculations show that they have also been observed experimentally, although not recognized as vortices. Their observation in (e,2e) measurements shows that vortices play an important role in electron correlations related to the transfer of angular momentum between incident and ejected electrons. The vortices significantly extend the list of known features that summarize the general picture of electron correlations in impact ionization.


Longitudinal hydrodynamic characteristics in reservoir tributary embayments and effects on algal blooms.
Three Gorges Reservoir (TGR) is one of the largest man-made lakes in the world. Since the impoundment in 2003, however, algal blooms have been often observed in the tributary embayments. To control the algal blooms, a thorough understanding of the hydrodynamics (e.g., flow regime, velocity gradient, and velocity magnitude and direction) in the tributary embayments is particularly important. Using a calibrated three-dimensional hydrodynamic model, we carried out a hydrodynamic analysis of a typical tributary embayment (i.e., Xiangxi Bay) with emphasis on the longitudinal patterns. The results show distinct longitudinal gradients of hydrodynamics in the study area, which can be generally characterized as four zones: riverine, intermediate, lacustrine, and mainstream influenced zones. Compared with the typical longitudinal zonation for a pure reservoir, there is an additional mainstream influenced zone near the mouth due to the strong effects of TGR mainstream. The blooms are prone to occur in the intermediate and lacustrine zones; however, the hydrodynamic conditions of riverine and mainstream influence zones are not propitious for the formation of algal blooms. This finding helps to diagnose the sensitive areas for algal bloom occurrence.


Short communication: Different mutation patterns in subtype CRF06_cpx after mother-to-child transmission.
Abstract Development of drug resistance mutation patterns (DRMP) in HIV after treatment failure depends on the drugs used in the failing regimen. However, selected patterns may not be unique; there is evidence that selection of DRMP for nelfinavir is dependent on subtype and/or background polymorphisms. Here we describe the selection of DRMP in a mother and son infected with subtype CRF06_cpx by mother-to-child transmission. Four years after delivery the mother received stavudine/lamivudine/nelfinavir as first-line therapy. Genotypic resistance tests (GRT) during follow-up showed selection of M184V/L283I in reverse transcriptase (RT) and H63Q/A71V/L90M in protease (PR). The child started treatment 8 months after birth with stavudine/didanosine/nelfinavir followed by an intensification period with efavirenz. Due to toxicity, efavirenz was removed from the regimen again. GRT during follow-up showed selection of L74V/K103N/M184V/M230L in RT and M46I/H63Q/N88S in PR. The viral load (VL) of the mother was initially undetectable followed by intermediate replication (1000-21,000 copies/ml), whereas the child had both periods of undetectable VL and low-level replication. Although both patients were infected with the same virus and treated with the same protease inhibitor, different DRMPs were selected. Whether the nucleoside backbone, course of antiretroviral therapy, or different host environment is responsible for this variability must be determined in larger studies.


Acute presentation of koch's abdomen in children: Our experience.
To analyse our experience with acute presentations of abdominal tuberculosis (TB) in children for early diagnosis and management. From December 2010 to April 2016, available electronic and operation theatre (OT) records of 17 patients with confirmed diagnosis of abdominal TB were analysed retrospectively. Parameters reviewed were age, sex, presentations, diagnostic investigations, surgery/intervention performed, final outcome and follow-up. Out of 17 patients, 6 (35.3%) were already operated elsewhere. The duration of symptoms ranged from 4 to 58 weeks. Abdominal pain was present in all cases whereas 11 (64.7%) had abdominal distension, 16 (94.1%) fever, 14 (82.3%) ascites, 9 (52.9%) vomiting, 14 (82.3%) weight loss, 6 (35.3%) anorexia and 4 (23.5%) night sweat. All patients needed surgical intervention for definitive diagnosis. Thirteen (76.5%) out of 17 patients managed by staged surgery and primary anastomosis/repair/adhesiolysis were done in 4 (23.5%) patients. The main post-operative problems were wound infections (8; 47.1%), subacute bowel obstruction (6; 35.3%) and chest infections (12; 70.6%). Follow-up period ranged from 3 months to 5.5 years. Abdominal TB should always be considered in differential diagnosis in children presenting with abdominal pain/distension, fever and ascites or with abdominopelvic mass. Recurrent bowel obstruction or anastomotic disruptions also give clues of its diagnosis. A careful history of illness, high index of suspicion, ascitic fluid adenosine deaminase or polymerase chain reaction for Mycobacterium needed for early diagnosis. Prompt minimal surgical interventions, preferred diversion over primary anastomosis, algorithmic vigilant post-operative care and early antitubercular treatment required for success in acute crisis.


Accumulation of electrophilic aldehydes during postovulatory aging of mouse oocytes causes reduced fertility, oxidative stress, and apoptosis.
With increasing periods of time following ovulation, the metaphase II (MII)-stage oocyte experiences overproduction of reactive oxygen species and elevated levels of lipid peroxidation that are implicitly linked with functional deficiencies acquired during postovulatory oocyte aging. We have demonstrated that the electrophilic aldehydes 4-hydroxynonenal (4HNE), malondialdehyde, and acrolein are by-products of nonenzymatic lipid peroxidation in the murine MII-stage oocyte, adducting to multiple proteins within the cell. The covalent modification of oocyte proteins by these aldehydes increased with extended periods of time postovulation; the mitochondrial protein succinate dehydrogenase (SDHA) was identified as a primary target for 4HNE adduction. Time- and dose-dependent studies revealed that exposure to elevated levels of electrophilic aldehydes causes mitochondrial reactive oxygen species production, lipid peroxidation, loss of mitochondrial membrane potential, and eventual apoptosis within the MII oocyte, presumably as a consequence of electron transport chain collapse following SDHA adduction. Additionally, we have determined that short-term exposure to low doses of 4HNE dramatically impairs the oocyte's ability to participate in fertilization and support embryonic development; however, this loss of functionality can be prevented by supplementation with the antioxidant penicillamine. In conclusion, this study has revealed that the accumulation of electrophilic aldehydes is linked to postovulatory oocyte aging, causing reduced fertility, oxidative stress, and apoptosis of this highly specialized cell. These data highlight the importance of timely fertilization of the mammalian oocyte postovulation and emphasize the potential advantages associated with antioxidant supplementation of oocyte culture medium in circumstances where reinsemination of oocytes may be desirable (i.e., rescue intracytoplasmic sperm injection), or where in vitro fertilization may be delayed.


A consensus report on appropriate treatment optimization and transitioning in the management of moderate-to-severe plaque psoriasis.
There is limited information on systemic and biological treatment optimization and transitioning in routine clinical practice. To provide practical guidance on treatment optimization and transitioning for moderate-to-severe plaque psoriasis. Dermatologists from 33 countries contributed to the Transitioning Therapies programme. Fourteen questions were identified. Answers were drafted based on systematic literature reviews (7/14 questions) and expert opinion (7/14 questions). Using a modified Delphi procedure, dermatologists from 30 countries voted on their level of agreement with each draft answer (scale: 1-9, strong disagreement to strong agreement). Consensus was defined as ≥75% of participants scoring within the 7-9 range. Consensus was achieved on the answers to all questions. Recommendations for the use of cyclosporine and methotrexate were agreed. Transitioning from a conventional systemic therapy to a biological agent may be done directly or with an overlap (if transitioning is required because of lack of efficacy) or potentially with a treatment-free interval (if transitioning is required for safety reasons). Combination therapy may be beneficial. Continuous therapy for patients on biologicals is strongly recommended. However, during successful maintenance with biological monotherapy, a dosage reduction may be considered to limit drug exposure, although this may carry the risk of decreased efficacy. Switching biologicals for reasons of efficacy should be done without a washout period, but switching for reasons of safety may require a treatment-free interval. This consensus provides practical guidance on treatment optimization and transitioning for moderate-to-severe plaque psoriasis, based on literature reviews and the expert opinion of dermatologists from across the globe.


A comparison of 2 doses of antenatal dexamethasone for the prevention of respiratory distress syndrome: an open-label, noninferiority, pragmatic randomized trial.
Antenatal corticosteroids have been used for the prevention of respiratory complications, intraventricular hemorrhage, necrotizing enterocolitis, and other adverse neonatal outcomes for over 50 years, with limited evidence about their optimal doses. Higher steroid doses or frequencies of antenatal corticosteroids in preterm newborns pose adverse effects such as prolonged adrenal suppression, negative effects on fetal programming and metabolism, and increased risks of neurodevelopmental and neuropsychological impairments. Conversely, lower doses of antenatal corticosteroids may be an effective alternative to induce fetal lung maturation with less risk to the fetus. Late preterm births represent the largest population of all preterm neonates, with a respiratory distress syndrome risk of 8.83%. Therefore, determining the optimal antenatal corticosteroid dosage is of particular importance for this population. This study aimed to compare the efficacy of 5-mg and 6-mg dexamethasone in preventing neonatal respiratory distress syndrome in women with preterm births at 320 to 366 weeks of gestation. This was an open-label, randomized, controlled, noninferiority trial. Singleton pregnant women (n=370) at 320 to 366 weeks of gestation with spontaneous preterm labor or preterm premature rupture of membranes were enrolled. They were randomly assigned (1:1) to a 5-mg or 6-mg dexamethasone group. Dexamethasone was administered intramuscularly every 12 hours for 4 doses or until delivery. The primary outcome was the reduction in neonatal respiratory distress syndrome cases, whereas the secondary outcomes were any adverse maternal or neonatal events. Between December 2020 and April 2022, 370 eligible women, anticipating deliveries within the gestational range of 32 0/7 to 36 6/7 weeks, willingly participated in the study. They were evenly split, with 185 women assigned to the 5-mg group and 185 to the 6-mg group. The study revealed that the demographic profiles of the participants in the 2 groups were remarkably similar, with no statistically significant disparities (P>.05). It is noteworthy that most of these women gave birth after 34 weeks of gestation. Despite a substantial proportion not completing the full course of steroid treatment, the 5-mg dose exhibited noninferiority compared with the 6-mg dose of dexamethasone, as indicated by a modest proportional difference of 0.5% (95% confidence interval, -2.8 to 43.9). Neonatal respiratory distress syndrome occurred in a relatively low percentage of newborns in both groups, affecting 2.2% in the 5-mg group and 1.6% in the 6-mg group. Notably, the risk difference of 0.6% fell comfortably within the predefined noninferiority threshold of 10%. Our study suggests that a 5-mg dexamethasone dose is noninferior to a standard 6-mg dose in preventing neonatal respiratory distress syndrome in preterm births.


Insulin-like growth factor (IGF)-II and insulin, but not IGF-I, are mitogenic for fetal rat adrenal cells in vitro.
The agents controlling growth of the fetal adrenal gland are poorly defined. The purpose of the present study was to determine the factors required to promote proliferation of adrenal cells obtained from fetal rats at 20 days of gestation and grown in monolayer cell culture under serum-free conditions. Insulin stimulated [3H] thymidine incorporation into DNA at all concentrations (0.01-10 mg/l) tested. Rat insulin-like growth factor (IGF)-II in the presence of insulin promoted a dose-dependent increase in mitogenic activity, with a half-maximal concentration of approximately 1 microgram/l; IGF-II had no effect in the absence of insulin. There was no significant effect of IGF-I on mitogenic activity in the presence or absence of insulin. Adrenal cell DNA synthesis was not stimulated by ACTH, several ACTH-related peptides, a variety of known growth factors, several steroids, or conditioned medium from fetal adrenal cells. We conclude that in the presence of insulin, IGF-II is a specific growth factor for the fetal rat adrenal. We also suggest that rat fetal adrenal cells, in common with other epithelial cell types under serum-free culture conditions, may respond to this progression factor without an obligatory requirement for an initial exposure to competence factors.


PCI with and without abciximab after upstream eptifibatide use: outcomes in high-risk patients.
Abciximab is often used to treat high-risk patients during percutaneous coronary intervention (PCI). Recent data indicate, however, that upstream and postprocedural treatment with low-dose glycoprotein (GP) IIb/IIIa inhibitors may be more beneficial than abciximab during and after PCI. Whether abciximab can be used safely or effectively during PCI for high-risk patients after upstream treatment with eptifibatide in patients with acute coronary syndromes (ACS) is not known. Clinical outcomes were evaluated in 289 patients with ACS who had upstream treatment with eptifibatide, and abciximab (EA) during PCI, and compared to 560 ACS patients who had both upstream and interventional treatment with eptifibatide (EE). Bleeding and vascular complications of the two groups were similar. Overall, 1-year major adverse cardiac event (MACE) rates were similar: 26.0% in the EA group and 25.2% in the EE group; p = 0.82. In patients with unstable angina, the hazard of MACE at 1 year was higher with EA than EE, 1.98 (1.23-3.18), due to significantly higher rates of repeat revascularization in the EA group. In patients with myocardial infarction (MI), the hazard of MI or death at 1 year was lower in the EA than the EE group, 0.50 (0.27-0.93). In this single-center observational study, the use of abciximab for PCI after upstream use of eptifibatide for ACS was safe. Abciximab was of no benefit in patients with unstable angina, but was associated with lower MI or death in patients with MI. These observations are consistent with recent findings indicating that abciximab is of benefit in patients with NSTEMI, but not lower-risk patients.


Cross-Parametric Generative Adversarial Network-Based Magnetic Resonance Image Feature Synthesis for Breast Lesion Classification.
Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) contains information on tumor morphology and physiology for breast cancer diagnosis and treatment. However, this technology requires contrast agent injection with more acquisition time than other parametric images, such as T2-weighted imaging (T2WI). Current image synthesis methods attempt to map the image data from one domain to another, whereas it is challenging or even infeasible to map the images with one sequence into images with multiple sequences. Here, we propose a new approach of cross-parametric generative adversarial network (GAN)-based feature synthesis (CPGANFS) to generate discriminative DCE-MRI features from T2WI with applications in breast cancer diagnosis. The proposed approach decodes the T2W images into latent cross-parameter features to reconstruct the DCE-MRI and T2WI features by balancing the information shared between the two. A Wasserstein GAN with a gradient penalty is employed to differentiate the T2WI-generated features from ground-truth features extracted from DCE-MRI. The synthesized DCE-MRI feature-based model achieved significantly (p = 0.036) higher prediction performance (AUC = 0.866) in breast cancer diagnosis than that based on T2WI (AUC = 0.815). Visualization of the model shows that our CPGANFS method enhances the predictive power by levitating attention to the lesion and the surrounding parenchyma areas, which is driven by the interparametric information learned from T2WI and DCE-MRI. Our proposed CPGANFS provides a framework for cross-parametric MR image feature generation from a single-sequence image guided by an information-rich, time-series image with kinetic information. Extensive experimental results demonstrate its effectiveness with high interpretability and improved performance in breast cancer diagnosis.


Chiral Perylene Materials by Ionic Self-Assembly.
Two chiral complexes (1-SDS and 1-SDBS) were prepared via the ionic self-assembly of a chiral perylene diimide tecton with oppositely charged surfactants. The effect of surfactant tail architecture on the self-assembly properties and supramolecular structure was investigated in detail using UV-vis, IR, circular dichroism, light microscopy, X-ray diffraction studies, and electron microscopy. The results obtained revealed the molecular chirality of the parent perylene tecton could be translated into supramolecular helical chirality of the resulting complexes via primary ionic interactions through careful choice of solvent and concentration. Differing solvent-dependent aggregation behavior was observed for these complexes as a result of the different possible noncovalent interactions via the surfactant alkyl tails. The results presented in this study demonstrate that ionic self-assembly (ISA) is a facile strategy for the production of chiral supramolecular materials based on perylene diimides. The structure-function relationship is easily explored here due to the wide selection and easy availability of common surfactants.


Control of manganese dioxide particles resulting from in situ chemical oxidation using permanganate.
In situ chemical oxidation using permanganate is an approach to organic contaminant site remediation. Manganese dioxide particles are products of permanganate reactions. These particles have the potential to deposit in the subsurface and impact the flow-regime in/around permanganate injection, including the well screen, filter pack, and the surrounding subsurface formation. Control of these particles can allow for improved oxidant injection and transport and contact between the oxidant and contaminants of concern. The goals of this research were to determine if MnO(2) can be stabilized/controlled in an aqueous phase, and to determine the dependence of particle stabilization on groundwater characteristics. Bench-scale experiments were conducted to study the ability of four stabilization aids (sodium hexametaphosphate (HMP), Dowfax 8390, xanthan gum, and gum arabic) in maintaining particles suspended in solution under varied reaction conditions and time. Variations included particle and stabilization aid concentrations, ionic content, and pH. HMP demonstrated the most promising results, as compared to xanthan gum, gum arabic, and Dowfax 8390 based on results of spectrophotometric studies of particle behavior, particle filtration, and optical measurements of particle size and zeta potential. HMP inhibited particle settling, provided for greater particle stability, and resulted in particles of a smaller average size over the range of experimental conditions evaluated compared to results for systems that did not include HMP. Additionally, HMP did not react unfavorably with permanganate. These results indicate that the inclusion of HMP in a permanganate oxidation system improves conditions that may facilitate particle transport.


The Implications of Cannabinoid-Induced Metabolic Dysregulation for Cellular Differentiation and Growth.
The endocannabinoid system (ECS) governs and coordinates several physiological processes through an integrated signaling network, which is responsible for inducing appropriate intracellular metabolic signaling cascades in response to (endo)cannabinoid stimulation. This intricate cellular system ensures the proper functioning of the immune, reproductive, and nervous systems and is involved in the regulation of appetite, memory, metabolism, and development. Cannabinoid receptors have been observed on both cellular and mitochondrial membranes in several tissues and are stimulated by various classes of cannabinoids, rendering the ECS highly versatile. In the context of growth and development, emerging evidence suggests a crucial role for the ECS in cellular growth and differentiation. Indeed, cannabinoids have the potential to disrupt key energy-sensing metabolic signaling pathways requiring mitochondrial-ER crosstalk, whose functioning is essential for successful cellular growth and differentiation. This review aims to explore the extent of cannabinoid-induced cellular dysregulation and its implications for cellular differentiation.


Fc receptors on granulocytes from patients with rheumatoid arthritis and Felty's syndrome.
Receptors for the Fc part of IgG on polymorphonuclear cells (FcR) of patients with rheumatoid arthritis (RA), Felty's syndrome (FS) and healthy controls (HC) were studied by means of a rosetting technique with rabbit IgG coated ox erythrocytes. When cold isolated polymorphonuclear cells (PMN) were incubated at room temperature the percentage of rosette forming PMN (RF-PMN) from HC was more than twice that measured directly after isolation at 4 degrees C. The same phenomenon was observed for PMN from patients with RA although the RF-PMN increased by only 1/3. In contrast warming of PMN from patients with FS did not influence the RF-PMN. The presence of surface bound immunoglobulins and intracytoplasmic immunoglobulins was measured by immunofluorescence and appeared to be inversely related to the RF-PMN. A good correlation between the results of the C1q binding assay (C1qBA) and the immunofluorescence score was observed but no correlation existed between the C1qBA and the RF-PMN. These results indicate that the number of PMN expressing FcR in patients with RA and FS is decreased presumably because of the phagocytosis of immune complex like material. The decrease in the availability of FcR may influence the functions of the PMN.


AB variant GM2 gangliosidosis: cerebrospinal fluid and neuropathologic characteristics.
A child with AB variant GM2 gangliosidosis who had progressive intellectual deterioration and seizures commencing at the age of 12 months is described. Neuronal loss, and neuronal and astrocytic inclusions characteristic of the gangliosidoses, were seen on cortical biopsy. GM2 ganglioside was detected in the CSF. As CNS ganglioside accumulation in this condition occurs in the presence of normal leukocyte hexosaminidase A and B levels, spinal fluid assay for GM2 ganglioside may serve as a valuable aid in diagnosis.


[Reef community structure at Falcón, Venezuela, before and after a mass mortality].
Morrocoy National Park used to be considered the most important continental coral reef of Venezuela. However, in January of 1996, there was a massive mortality of the benthic organisms for unknown reasons. The coral reef community was monitored since 1995, the year before the event, and yearly after that, until June 1999, by sampling linear transects and quadrats. A total of 26 hard corals were recorded in the study site (Playa Mero) in 1995 (36.56% cover), which already had some deterioration because 90.86% of the living coral cover was represented basically by four species, M. annularis with 51.36%, Colpophyllia natans with 18.22%, Agaricia agaricites with 11.58% and Porites porites with 9.70%. Three months after the event, living coral cover was only 4.84% and algae, particularly Dyctiota spp. covered most of the surface (81.89%). Benthic organisms suffered massive mortality over the whole depth gradient and in most park reefs. Even after three years the reef community shows highly perturbed conditions, with 85% of the total cover represented by the categories: dead coral, dead coral overgrowth by algae and sand. From the initial coral richness of the area (26 species) only nine species were observed although in very low cover (<1%), except for M. annularis and M. franksi, which presented lightly higher percentages.


The reliability and validity of the Oppositional Defiant Behavior Inventory.
The aim of this study was to develop an evaluation scale for use as a supplementary tool for the diagnosis of oppositional defiant disorder (ODD). The subjects were 98 Japanese children (91 males and 7 females), aged 6-15 years, diagnosed with attention deficit/hyperactivity disorder (ADHD) or ODD. Internal consistency, test-retest reliability, concurrent validity and divergent validity of the oppositional defiant behavior inventory (ODBI), an evaluation scale of oppositional defiant tendency, were examined. Cronbach's alpha coefficient of the ODBI was 0.925. The correlation coefficient between the test and the retest was 0.820 (p < 0.0001). Both the ODBI scores (test and retest) were correlated with the number of items that matched the ODD diagnostic criteria of DSM-IV (r = 0.660, 0.659, p < 0.001), and with the ODD-scale of Disruptive Behavior Disorders Rating Scale (r = 0.725, 0.654, p < 0.001). Compared with the ADHD group or controls, the ADHD and ODD group showed a significantly higher ODBI score at p < 0.0001. The concurrent use of this scale with clinical examination is expected to increase the accuracy of the diagnosis of ODD.


Amiloride augments TRAIL-induced apoptotic death by inhibiting phosphorylation of kinases and phosphatases associated with the P13K-Akt pathway.
We have previously shown that low extracellular pH (pHe) promotes cell killing by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In this study, we examined whether amiloride, an inhibitor of the Na(+)/H(+) antiporter capable of lowering the intracellular pH (pHi), can potentiate TRAIL-induced apoptotic death. Human prostate adenocarcinoma DU-145 cells were treated with various concentrations of TRAIL (10-200 ng/ml) and/or amiloride (0.1-1 mM) for 4 h. Amiloride, which caused little or no cytotoxicity by itself, enhanced TRAIL-induced apoptosis. The TRAIL-mediated activation of caspase, and PARP (poly (ADP-ribose) polymerase) cleavage were both promoted by amiloride. Western blot analysis showed that combined treatment with TRAIL and amiloride did not change the levels of TRAIL receptors (death receptor (DR)4, DR5, and DcR2 (decoy recepter 2) or antiapoptotic proteins (FLICE-inhibitory protein (FLIP), inhibitor of apoptosis (IAP), and Bcl-2). However, unlike pHe, amiloride promoted the dephosphorylation of Akt. Interestingly, amiloride also induced the dephosphorylation of P13K (phosphatidylinositol 3-kinase) and PDK-1 (phosphoinositide-dependent kinase-1) kinases along with PTEN (phosphatase and tensin homolog deleted on chromosome 10) and PP1alpha phosphatases. In vitro kinase assays revealed that amiloride inhibited phosphorylation of kinases and phosphatases by competing with ATP. Taken together, the present studies suggest that amiloride enhances TRAIL-induced cytotoxicity by inhibiting phosphorylation of the PI3K-Akt pathway-associated kinases and phosphatases.


Cellular and Molecular Evidence of Multiple Sclerosis Diagnosis and Treatment Challenges.
Multiple sclerosis (MS) is a chronic autoimmune disease that impacts the central nervous system and can result in disability. Although the prevalence of MS has increased in India, diagnosis and treatment continue to be difficult due to several factors. The present study examines the difficulties in detecting and treating multiple sclerosis in India. A lack of MS knowledge among healthcare professionals and the general public, which delays diagnosis and treatment, is one of the significant issues. Inadequate numbers of neurologists and professionals with knowledge of MS management also exacerbate the situation. In addition, MS medications are expensive and not covered by insurance, making them inaccessible to most patients. Due to the absence of established treatment protocols and standards for MS care, India's treatment techniques vary. In addition, India's population diversity poses unique challenges regarding genetic variations, cellular and molecular abnormalities, and the potential for differing treatment responses. MS is more difficult to accurately diagnose and monitor due to a lack of specialized medical supplies and diagnostic instruments. Improved awareness and education among healthcare professionals and the general public, as well as the development of standardized treatment regimens and increased investment in MS research and infrastructure, are required to address these issues. By addressing these issues, it is anticipated that MS diagnosis and treatment in India will improve, leading to better outcomes for those affected by this chronic condition.


Surgical procedures in patients with Glanzmann's thrombasthenia: case series and literature review.
Glanzmann's thrombasthenia is a rare platelet function disorder with an autosomal recessive pattern of inheritance. Achieving haemostasis in such patients who undergo surgical procedures always poses a significant challenge. Herein we report six cases of Glanzmann's thrombasthenia, who underwent nine surgeries under the cover of platelet-rich concentrates with or without recombinant activated factor VII . Of these, five were major surgeries such as thyroidectomy, laparotomy, Hartmann's procedure, reversal of Hartmann's procedure and a complete dental extraction. All five procedures were successfully done without any major bleeding. The major cost incurred in these procedures is due to the large number of blood products used and recombinant activated factor VII if used.


New sonographic techniques for the diagnosis and treatment of hepatocellular carcinoma.
Ultrasound (US) contrast agents such as Levovist and Sonazoid are now commercially available in Japan. Innovative contrast agents and ultrasound technologies have dramatically changed both diagnostic and treatment strategies for hepatocellular carcinoma (HCC). Contrast-enhanced US is extremely useful in the differential diagnosis of hepatic tumors as well as in evaluation of post-treatment response of HCC after lipiodol transarterial chemoembolization and radio frequency ablation. Harmonic US sensitively detects residual cancer cells in HCC patients after treatment, to facilitate accurate guidance for needle insertion for US monitoring; no other imaging modalities, including computed tomography (CT) or magnetic resonance imaging (MRI), have such capability. In 2005, the breakthrough technology of pure arterial phase imaging, which depicts only intranodular arterial accumulated maximum intensity projection images, was developed from advanced raw data storing and accumulation technologies. This technique can clearly identify whether blood supplyin the tumor is of arterial or portal origin, to facilitate the non-invasive characterization of nodular lesions associated with liver cirrhosis. Again, CT or MRI do not have such capabilities. This innovative technique can help differentiate premalignant lesions from overt HCC. Concurrent real-time imaging of multi-detector CT and US, known as real-time virtual sonography, has recently become available. This technique greatly facilitates the treatment guidance for HCC. These newly introduced sonographic techniques are dramatically changing the diagnostic and therapeutic strategies for HCC, which are expected to improve the prognosis of HCC patients.


A new approach for contrast-enhanced X-ray imaging of the left atrium and pulmonary veins for atrial fibrillation ablation: rotational angiography during adenosine-induced asystole.
Atrial fibrillation ablation is a complex procedure that requires detailed anatomic information about left atrium (LA) and pulmonary veins (PVs). The goal of this study was to test rotational angiography of the LA during adenosine-induced asystole as an imaging tool in patients undergoing atrial fibrillation ablation. Seventy patients with paroxysmal or persistent atrial fibrillation undergoing PV isolation were included. After transseptal puncture, adenosine (30 mg) was given intravenously, and during atrioventricular block, contrast medium was directly injected in the LA; a rotational angiography was performed (right anterior oblique 55 degrees to left anterior oblique 55 degrees). Rotational angiography images were assessed qualitatively in all patients and quantitatively in 45 patients in comparison with computed tomography (CT) images. The majority of rotational angiography imaging data (94%) were deemed at least 'useful' in delineating the LA-PV anatomy. The so-called 'ridge' between left superior PV and left atrial appendage was delineated in 90% of the patients. All accessory PVs were independently identified by rotational angiography and CT. A blinded quantitative comparison of PV ostial diameters showed an excellent correlation between rotational angiography and CT measurements (r > 0.90 for all PVs). No serious adverse effects occurred in association with adenosine. Intra-procedural contrast-enhanced rotational angiography of the LA-PV during adenosine-induced asystole is feasible and provides anatomical information of high diagnostic value for atrial fibrillation ablation.


Stereoselective synthesis of (-)-amphidinolide E.
The total synthesis of (-)-amphidinolide E was accomplished by following a synthetic scheme that incorporates the labile C2 stereocenter at a very late stage. The oxolane unit was prepared by beta-alkoxyacrylate radical cyclization. The enyne metathesis reaction was employed for the synthesis of the side chain. The Kocienski-Julia reaction was used for the union of the two major fragments, and the Kita macrolactonization protocol was used for macrolide synthesis.


Endoscopic closure instead of surgery to close an ileal pouch fistula with the over-the-scope clip system.
An ileal pouch fistula is an uncommon complication after an ileal pouch anal anastomosis. Most patients who suffer from an ileal pouch fistula will need surgical intervention. However, the surgery can be invasive and has a high risk compared to endoscopic treatment. The over-the-scope clip (OTSC) system was initially developed for hemostasis and leakage closure in the gastrointestinal tract during flexible endoscopy. There have been many successes in using this approach to apply perforations to the upper gastrointestinal tract. However, this approach has not been used for ileal pouch fistulas until currently. In this report, we describe one patient who suffered a leak from the tip of the "J" pouch and was successfully treated with endoscopic closure via the OTSC system. A 26-year-old male patient had an intestinal fistula at the tip of the "J" pouch after an ileal pouch anal anastomosis procedure. He received endoscopic treatment via OTSC under intravenous anesthesia, and the leak was closed successfully. Endoscopic closure of a pouch fistula could be a simpler alternative to surgery and could help avoid surgery-related complications.


MRI catheterization in cardiopulmonary disease.
Diagnosis and prognostication in patients with complex cardiopulmonary disease can be a clinical challenge. A new procedure, MRI catheterization, involves invasive right-sided heart catheterization performed inside the MRI scanner using MRI instead of traditional radiographic fluoroscopic guidance. MRI catheterization combines simultaneous invasive hemodynamic and MRI functional assessment in a single radiation-free procedure. By combining both modalities, the many individual limitations of invasive catheterization and noninvasive imaging can be overcome, and additional clinical questions can be addressed. Today, MRI catheterization is a clinical reality in specialist centers in the United States and Europe. Advances in medical device design for the MRI environment will enable not only diagnostic but also interventional MRI procedures to be performed within the next few years.


Redox modulation of the inotropic response to dobutamine is impaired in patients with heart failure.
It has been suggested that oxidative stress contributes to impaired left ventricular (LV) contractility in the setting of heart failure (HF). To test this hypothesis, we studied the effect of an antioxidant on contractility at rest and in response to dobutamine in 10 HF patients. We hypothesized that vitamin C would augment contractility in HF and that this effect would be of a greater magnitude in HF patients compared with patients with normal LV (NLV) function. Data from 10 patients with NLV function who participated in this study are included in this report and have been published elsewhere. A micromanometer-tipped catheter was introduced into the LV. In the experimental protocol, an infusion catheter was positioned in the left main coronary artery. The peak positive rate of change of LV pressure (LV +dP/dt) was measured in response to the intravenous infusion of dobutamine before and during the intracoronary infusion of vitamin C (96 mg/min). Vitamin C had no effect on basal LV +dP/dt in either HF or NLV groups. The infusion of vitamin C augmented the LV +dP/dt response to dobutamine by 22 +/- 4% in the NLV function group. In contrast, vitamin C had no effect on the inotropic response to dobutamine in the HF group. In the control protocol, without vitamin C, no differences were observed between responses to two sequential dobutamine infusions in either group (HF, n = 11; NLV, n = 9). Therefore, a positive effect of vitamin C on contractility was limited to patients with NLV function. The absence of this effect in HF patients may suggest that normal redox responsiveness is lost in this disease state.


New spiral γ-lactone enantiomers from the plant endophytic fungus Pestalotiopsis foedan.
(-)-(4S, 8S)-Foedanolide (1a) and (+)-(4R, 8R)-foedanolide (1b), a pair of new spiro-γ-lactone enantiomers, were isolated from the fermentation broth of the plant endophytic fungus Pestalotiopsis foedan by HPLC using a chiral column, achieving over 7% ee. Their structures and absolute configurations were determined on the basis of extensive analysis of NMR spectra combined with computational methods via calculation of the electronic circular dichroism (ECD) and optical rotation (OR). Compounds 1a and 1b showed moderate activities against HeLa, A-549, U-251, HepG2 and MCF-7 tumor cell lines.


Cytotoxicity of three new triazolo-pyrimidine derivatives against the plant trypanosomatid: Phytomonas sp. isolated from Euphorbia characias.
There is no effective chemotherapy against diseases caused by Phytomonas sp., a plant trypanosomatid responsible for economic losses in major crops. We tested three triazolo-pyrimidine complexes [two with Pt(II), and another with Ru(III)] against promastigotes of Phytomonas sp. isolated from Euphorbia characias. The incorporation of radiolabelled precursors, ultrastructural alterations and changes in the pattern of metabolite excretion were examined. Different degrees of toxicity were found for each complex: the platinum compound showed an inhibition effect on nucleic acid synthesis, provoking alterations on the levels of mitochondria, nucleus and glycosomes. These results, together with others reported previously in our laboratory about the activity of pyrimidine derivatives, reflect the potential of these compounds as agents in the treatment of Phytomonas sp.


Imprisoning Pregnant and Parenting Women: A Focus on Social Justice, Equal Rights, and Equality.
The mass incarceration of pregnant and parenting women is a serious problem in the United States. African American women and other women of color are most burdened by mass incarceration. This article outlines the problems with health care delivery in correctional facilities. It is argued that correctional facilities are not the place for pregnant and parenting women. A policy focus is needed that takes a public health approach. There are promising alternative policies that integrate a public health approach, improve treatment outcomes for women, and provide an alternative to incarceration. This problem is discussed through the lens of the Grand Challenges for Social Work. Alternative policies and programs are recommended that align with a public health approach and directly target the pathways for imprisonment. This issue requires a call for policy action to challenge the inequality and social justices inherent in this problem. The grand challenges offer a blueprint in which to develop effective policy approaches.


High-level multilineage engraftment of human cord blood cells in SCID mice.
Cord blood is increasingly used as an alternative to bone marrow transplantation in pediatric patients. Therefore, to study cord blood-derived hematopoiesis in vivo we are developing a xenogeneic transplantation model using immunodeficient SCID mice.


Soret coefficients in some water-methanol, water-ethanol, and water-isopropanol systems.
In this article, we re-examine the published experimental values of the Soret coefficients of a few water-alcohol systems at a mean temperature of 37.5 degrees C, because we feel that these published values (including microgravity values) are doubtful. The main technique applied is the use of thermogravitational columns to determine the thermodiffusion coefficient. The obtained values did not agree with the published values; worse, sometimes the sign was different.


Prevalence and characterization of ESBL-producing Escherichia coli in healthy pregnant women and hospital environments in Benin: an approach based on Tricycle.
Extended-Spectrum Beta-Lactamase (ESBL)-producing Enterobacterales are recognized as significant pathogens due to their resistance to multiple antibiotics. This study aimed to determine the prevalence of ESBL-producing Escherichia coli (E. coli) in different settings, including healthy pregnant women, the food chain, and the environment of tertiary hospitals in Benin. Samples were collected from various sources, including fecal samples from healthy pregnant women, food samples from hospital canteens, and hospital effluents from four tertiary hospitals in southern Benin. Fecal samples were plated on MacConkey agar supplemented with cefotaxime (4 μg/mL), while food and water samples were plated on Tryptone Bile X agar supplemented with cefotaxime (4 μg/mL). Urea indole tests were used for preliminary identification of E. coli colonies, followed by confirmation of ESBL production using the double disk synergy technique. Antibiotic susceptibility testing of ESBL-producing E. coli strains was conducted using the disk diffusion method on MH agar. Polymerase Chain Reaction (PCR) was used to investigate the presence of ESBL-encoding genes. Among the 296 fecal samples collected from four tertiary hospitals, ESBL-producing E. coli was isolated from 22.30% (66) of the samples. All E. coli isolates from hospital effluents exhibited ESBL production, while ESBL-producing E. coli was not detected in food and drinking water samples. The analysis of variable associations showed no significant associations (p > 0.05) for the studied factors. Antibiotic susceptibility testing revealed high resistance rates among the ESBL-Ec isolates against several tested antibiotics, including amoxicillin, aztreonam, ceftriaxone, ciprofloxacin, and trimethoprim-sulfamethoxazole. However, most isolates remained susceptible to ertapenem, amoxicillin-clavulanate, and imipenem. The most prevalent ESBL-encoding genes were blaTEM (37.50%), blaOXA-1 (19.44%), and blaSHV (11.11%), while a smaller proportion of isolates carried blaCTXM-1/blaCTXM-15 (5.55%) and blaCTXM-9. This study provides insights into the prevalence of ESBL-producing E. coli carriage in the feces of healthy pregnant women in southern Benin. Additionally, it highlights hospital wastewater as a potential reservoir of ESBL-producing bacteria in the environment. The detection of ESBL-producing E. coli in hospital effluents raises concerns about the dissemination of antibiotic resistance genes into the environment. The high resistance rates observed among ESBL-Ec isolates against commonly used antibiotics emphasize the urgent need for antimicrobial stewardship and infection control measures. The identification of prevalent ESBL-encoding genes contributes to understanding the genetic basis of ESBL resistance in the studied population. Further research is warranted to explore the mechanisms of transmission and potential interventions to mitigate the spread of ESBL-producing Enterobacterales.


Arylsulfatase A activities in urine and tissues taken from bladder cancer patients.
Urinary arylsulfatase A activity expressed as units/mg of urinary creatinine was significantly increased in bladder cancer patients, but not in patients with other genitourinary tract disorders, such as cystitis, urethritis and prostatic cancer, nor in patients with non-urological malignant diseases. The urinary enzyme activity was positively correlated with the stage of the bladder cancer, while post surgical follow-up revealed a marked decrease of the activity. Arylsulfatase A activity was also shown to be higher in malignant than in normal bladder tissue, demonstrating the activity to be a function of the grade of the tumor. Furthermore, the isoelectric point (pI 5.2-5.3) of the tissue enzyme in the bladder tumor coincided with that of the urine enzyme from the same cancer patients; the pI of the enzyme in urine from normal subjects was 4.7. These results suggest that most of the urinary arylsulfatase A in bladder cancer originates from tumor tissue.


Speciation analysis of mercury in seawater from the lagoon of Venice by on-line pre-concentration HPLC-ICP-MS.
A method based on the coupling of HPLC with ICP-MS with an on-line pre-concentration micro-column has been developed for the analysis of inorganic and methyl mercury in the dissolved phase of natural waters. This method allows the rapid pre-concentration and matrix removal of interferences in complex matrices such as seawater with minimal sampling handling. Detection limits of 0.07 ng L(-1) for inorganic mercury and 0.02 ng L(-1) for methyl mercury have been achieved allowing the determination of inorganic mercury and methyl mercury in filtered seawater from the Venice lagoon. Good accuracy and reproducibility was demonstrated by the repeat analysis of the certified reference material BCR-579 coastal seawater. The developed HPLC separation was shown to be also suitable for the determination of methyl mercury in extracts of the particulate phase.


Neuroeconomics: an overview from an economic perspective.
Until now, economic theory has not systematically integrated the influence of emotions on decision-making. Since evidence from neuroscience suggests that decision-making as hypothesized in economic theory depends on prior emotional processing, interdisciplinary research under the label of "neuroeconomics" arose. The key idea of this approach is to employ recent neuroscientific methods in order to analyze economically relevant brain processes. This paper aims to provide an overview of the current state of neuroeconomic research by giving a brief description of the concept of neuroeconomics, outlining methods commonly used and describing current studies in this new research area. Finally, some future prospects and limitations are discussed.


Social support, physical functioning, and cognitive functioning among older African American adults.
Social support and functional ability are related to a number of outcomes in later life among African Americans, including cognitive performance. This study examined how providing and receiving social support was related to fluid and crystallized cognitive abilities among aging African American adults after accounting for functional limitations, age, education, sex, income, and self-reported health. Data from 602 African American adults (M = 69.08, SD = 9.74; 25% male) were analyzed using latent variable modeling. Fluid ability was a second-order factor indicated by measures that assessed verbal memory, working memory, perceptual speed, and inductive reasoning. Crystallized ability was a first-order factor indicated by three measures that assessed vocabulary (Shipley Verbal Meaning Test and parts A and B of the ETS Vocabulary Test). Results indicated that the receipt of social support was negatively related to both fluid and crystallized abilities, while the provision of support was positively related to fluid and crystallized ability. Follow-up tests found that the receipt of support was more strongly related to fluid ability than crystallized ability. There was no significant difference regarding the relationship of provision of support with fluid ability compared to crystallized ability. Results discuss the importance of considering the social context of older adults when examining cognitive ability.


Continuous-variable hyperentanglement in a parametric oscillator with orbital angular momentum.
We describe continuous-variable hyperentanglement in polarization and orbital angular momentum modes of an optical parametric oscillator. The quantum stochastic equations for the multimode parametric interaction are derived and solved allowing for calculation of the quadrature noise spectra that characterize continuous-variable entanglement. As a main result, we predict simultaneous entanglement between different combinations of amplitude and phase quadratures of the interacting modes. We also propose experimental setups to access the different kinds of entanglement.


[Pathogenesis and progression of scirrhous carcinoma].
The aim of the present paper is to elucidate the pathogenesis of gastric scirrhous carcinoma with special reference to fibrogenesis in cancer stroma and to the mode of cancer invasions. First, there are two hypotheses concerning the origin of the marked increase of collagen fibers in this type of carcinoma. One is thought to be production by fibroblasts stimulated by cancer cells; the other is synthesis by neoplastic cells. Our studies revealed that gastric cancer cells enhanced collagen production by fibroblasts in vitro, suggesting the contribution to the formation of stromal collagen in human gastric scirrhous cancer. However, one of four gastric scirrhous cancer cell lines, NKPS, was found to slightly from collagen fibers in the brain of the nude mouse. We also calculated the number of fibroblastic cells in gastric scirrhous and normal stroma by microscopical image analysis. The results showed that fibroblastic cells in scirrhous stroma were increased four-fold over those in normal stroma. This finding suggests that the mechanism by which fibrous stroma is produced in scirrhous carcinoma may be affected by the increased fibroblastic cells which were stimulated by many kinds of growth factors produced by cancer cells. It is also well known that the infiltrative growth and dispersion of scirrhous cancer cells within the gastric wall is very fast. To assess the mode of cancerous invasion of this carcinoma, we examined the urokinase-type plasminogen activator (uPA) activity of both types of cells (cancer cells and fibroblasts) with a coculture method. Scirrhous cancer cells enhanced production of uPA by fibroblasts. However, non-scirrhous gastric cancer cells produced much uPA by themselves. This finding suggests that scirrhous cancer cells can invade the gastric wall by use of uPA produced by enhanced fibroblasts, but that non-scirrhous cancer cells synthesize much uPA by themselves and can infiltrate the gastric wall.


[Cutaneous panarteritis nodosa: suggestion of diagnostic assessment for a benign disorder. 2 personal cases and review of the literature].
The diagnosis of cutaneous panarteritis nodosa, a local, isolated condition of good prognosis, requires the elimination of any systemic involvement. Two personal cases, together with a review of the literature, serve to demonstrate the benign nature of the condition, with the absence of systemic complications during a mean medical follow-up of 9 years. However, the condition is not entirely innocuous since it required the administration of corticosteroids in 71% of cases. The outcome was complete recovery in 32% of cases, and improvement or stabilisation in 51%, with no information provided in 16%. Complete recovery was obtained in the author's two cases: one spontaneously and one with corticosteroid therapy. The good prognosis justifies the suggestion of a relatively non-invasive diagnostic assessment. Medical follow-up is required if symptomatology persists or if steroids are prescribed, but is not necessary when there is complete recovery.


Acetylcholine increases intracellular Ca2+ in taste cells via activation of muscarinic receptors.
Previous studies suggest that acetylcholine (ACh) is a transmitter released from taste cells as well as a transmitter in cholinergic efferent neurons innervating taste buds. However, the physiological effects on taste cells have not been established. I examined effects of ACh on taste-receptor cells by monitoring [Ca2+]i. ACh increased [Ca2+]i in both rat and mudpuppy taste cells. Atropine blocked the ACh response, but D-tubocurarine did not. U73122, a phospholipase C inhibitor, and thapsigargin, a Ca2+-ATPase inhibitor that depletes intracellular Ca2+ stores, blocked the ACh response. These results suggest that ACh binds to M1/M3/M5-like subtypes of muscarinic ACh receptors, causing an increase in inositol 1,4,5-trisphosphate and subsequent release of Ca2+ from the intracellular stores. A long incubation with ACh induced a transient response followed by a sustained phase of [Ca2+]i increase. In Ca2+-free solution, the sustained phases disappeared, suggesting that Ca2+ influx is involved in the sustained phase. Depletion of Ca2+ stores by thapsigargin alone induced Ca2+ influx. These findings suggest that Ca2+ store-operated channels may be present in taste cells and that they may participate in the sustained phase of [Ca2+]i increase. Immunocytochemical experiments indicated that the M1 subtype of muscarinic receptors is present in both rat and mudpuppy taste cells.


Sympathetic skin response in patients with spinal cord injury.
To assess the effectiveness of sympathetic skin response in evaluating peripheral sympathetic nerve activity of patients with spinal cord injury, and to report on the basic properties of sympathetic skin response. Sympathetic skin response evoked by electrical stimulation was recorded from the palms and soles of healthy volunteers and patients with spinal cord injury. Sympathetic skin response was recorded in 17 healthy volunteers and 14 patients with spinal cord injury. Of the 4 waveforms, the shortest latency was obtained from the palm; the sympathetic skin response was 1.2 to 1.4 ms at all stimulated sites, 1.9 to 2.0 ms at the sole, with a difference of about 0.6 ms between the palm and the sole. None of the patients with spinal cord injury responded at either the upper or lower limbs. In patients with a thoracic cord injury, some responded at the upper limbs but none at the lower limbs; some responded at neither upper nor the lower limbs; and some responded at both upper and lower limbs. The conducting pathway of sympathetic skin response in the spinal cord for the upper limbs descends to the upper thoracic cord (T4-6), and the conducting pathway for the lower limbs departs from the spinal cord at the lower thoracic cord (T9-10). It appears that sympathetic skin response should be used for the evaluation and morbid investigation of the functional abnormalities of the sympathetic nervous system in patients with spinal cord lesions such as spinal cord injuries, cervical spondylosis, and spinal canal stenosis.


Self-assembled colloidal crystals from ZrO2 nanoparticles.
Ordered three-dimensional (3-D) assemblies of nanocrystalline zirconia were synthesized from aqueous suspensions of ZrO(2) nanoparticles without the need for hydrocarbon surfactants or solvents to control colloidal crystal growth. Nanoparticles were suspended in mild acid and subsequently titrated from low to neutral pH. The solubility was reduced as the surfaces were neutralized, promoting assembly of the nanoparticles into ordered monoliths. TEM measurements indicated the formation of three-dimensional, hexagonal faceted, micrometer-sized colloidal crystals composed of 4 nm diameter ZrO(2) nanoparticles. Lacking organic surfactants, the colloidal crystals were exceptionally robust and were sintered at high temperatures (300-500 degrees C) for further stability. Small-angle X-ray scattering (SAXS) measurements demonstrate that the samples become progressively more amorphous above 350 degrees C, although some ordered domains of nanoparticles persist. Additionally, the heat treatment dramatically increases the surface area of the colloidal crystals as water and residual organics are desorbed, revealing highly controlled interstitial spaces and pores.


Optical barcoding of PLGA for multispectral analysis of nanoparticle fate in vivo.
Understanding of the mechanisms by which systemically administered nanoparticles achieve delivery across biological barriers remains incomplete, due in part to the challenge of tracking nanoparticle fate in the body. Here, we develop a new approach for "barcoding" nanoparticles composed of poly(lactic-co-glycolic acid) (PLGA) with bright, spectrally defined quantum dots (QDs) to enable direct, fluorescent detection of nanoparticle fate with subcellular resolution. We show that QD labeling does not affect major biophysical properties of nanoparticles or their interaction with cells and tissues. Live cell imaging enabled simultaneous visualization of the interaction of control and targeted nanoparticles with bEnd.3 cells in a flow chamber, providing direct evidence that surface modification of nanoparticles with the cell-penetrating peptide TAT increases their biophysical association with cell surfaces over very short time periods under convective current. We next developed this technique for quantitative biodistribution analysis in vivo. These studies demonstrate that nanoparticle surface modification with the cell penetrating peptide TAT facilitates brain-specific delivery that is restricted to brain vasculature. Although nanoparticle entry into the healthy brain parenchyma is minimal, with no evidence for movement of nanoparticles across the blood-brain barrier (BBB), we observed that nanoparticles are able to enter to the central nervous system (CNS) through regions of altered BBB permeability - for example, into circumventricular organs in the brain or leaky vasculature of late-stage intracranial tumors. In sum, these data demonstrate a new, multispectral approach for barcoding PLGA, which enables simultaneous, quantitative analysis of the fate of multiple nanoparticle formulations in vivo.


Progress in proteomics for clinical microbiology: MALDI-TOF MS for microbial species identification and more.
Although classical proteomic approaches are still used regularly in routine clinical diagnostic procedures, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) MS has recently moved into diagnostic microbiology laboratories. MALDI-TOF MS is currently replacing phenotypic microbial identification. Many laboratories now use MALDI-TOF MS for its high efficiency, both from a diagnostic and a cost-per-analysis point of view. The US FDA has now cleared two of the commercially available systems for in vitro diagnostics. This will further spark development of MS applications in antimicrobial susceptibility testing and epidemiology. This review summarizes the state of affairs of MALDI-TOF MS in clinical microbiology; however, this is an active field of research subject to rapid evolution. We emphasize assessment of the clinical relevance and studies focusing on data obtained through comparative analyses of different MALDI-TOF MS instrumentation and multicenter validation studies. The future of MALDI-TOF MS, including antimicrobial susceptibility testing and epidemiological typing, is also highlighted.


Identification of porcine Pneumocystis carinii as a genetically distinct organism by DNA amplification.
DNA was amplified from lung samples from three piglets infected with Pneumocystis carinii, using oligonucleotide primers designed to the P. carinii mitochondrial large subunit ribosomal RNA gene. The nucleotide sequence of the amplification product was determined and indicated lack of sequence variation among these pig-derived P. carinii samples at this locus. The data showed that porcine P. carinii was genetically distinct from P. carinii isolated from other mammalian host species.


Patient Satisfaction in an Outpatient Hand Surgery Office: A Comparison of English- and Spanish-Speaking Patients.
As health care in the United States transitions from a fee-for-service to an outcomes-based environment, patient satisfaction is increasingly incentivized and publicly reported. Despite the continued growth of the Latino population and concomitant rise in the demand for health care, relatively little is known regarding patient satisfaction in Spanish speakers. We sought to compare patient satisfaction with hand surgery office visits between Spanish- and English-speaking patients. Directly after the office visit, 150 patients (75 English speakers and 75 Spanish speakers) completed a sociodemographic survey, an 11-point ordinal rating of pain intensity, and a survey of satisfaction with the encounter using items derived from the CG-CAHPS (Clinician and Group-Consumer Assessment of Healthcare Providers and Systems) survey. Multivariable regression modeling was used to identify factors associated with patient dissatisfaction. Overall, 79% of Spanish-speaking patients were satisfied with the physician as compared with 91% of English speakers (P = .041). Compared with English-speaking patients, Spanish speakers were less likely to be satisfied with provider listening carefully (91% vs 100%, P = .007) and spending enough time with them (56% vs 93%, P < .001), as well as with waiting times (81% vs 96%, P = .005). There was no difference with regard to provider showing respect, clarity of communication, and explanation of what was done. Younger age and Spanish language were independent predictors of patient dissatisfaction. Spanish-speaking patients are less satisfied with the care provided in a hand surgery office. In light of the growing diversity of the US population and the fact that patient satisfaction is increasingly tied to reimbursement, additional research might identify potential areas of improvement from both the surgeon (eg, communication strategies, cultural competence) and patient (eg health literacy, expectations) perspectives.


A DBULSTM-Adaboost Model for Sea Surface Temperature Prediction.
Sea surface temperature (SST) is an important parameter to measure the energy and heat balance of sea surface. The change of sea surface temperature has an important impact on the marine ecosystem, marine climate and marine environment. Therefore, sea surface temperature prediction has become an significant research direction in the field of ocean. This article proposes a DBULSTM-Adaboost model based on ensemble learning. The model is composed of Deep Bidirectional and Unidirectional Long Short Term Memory (DBULSTM) and Adaboost strong learner. DBULSTM can capture the forward and backward dependence of time series, and the DBULSTM model is integrated with Adaboost strong learner to reduce the variance and bias of prediction and realize the short and medium term prediction of SST at a single point scale. Experimental results show that the model can improve the accuracy and stability of SST prediction. Experiments on the East China Sea and South China Sea with different prediction lengths show that the model is almost superior to other classical models in different sea areas and at different prediction levels. Compared with full-connected LSTM (FC-LSTM) model, the root-mean-square error is reduced by about 0.1.


Molecular epidemiology of human G2P[4] rotaviruses in Taiwan, 2004-2011.
In 2006, two rotavirus vaccines (Rotarix and RotaTeq) became available on the private market in Taiwan. Although vaccine coverage is currently low, molecular surveillance of rotavirus strains can provide pertinent information for evaluation of the potential impact of vaccine introduction and infection control. During January 2008-December 2011, children aged <5 years hospitalized with acute gastroenteritis were enrolled from sentinel surveillance hospitals in three geographic areas of Taiwan. Fecal specimens collected from enrolled patients were tested for rotavirus by enzyme immunoassay and reverse transcriptase-polymerase chain reaction. For genotyping, gene specific primer sets were used to amplify and sequence the genes encoding the neutralization antigens, VP7 and VP4. The resulting sequences were then subjected to phylogenetic analysis. In brief, a total of 4,052 fecal specimens were tested and 742 (18%) samples were positive for rotavirus. The annual range of rotavirus positive specimens varied between 16% and 20.7%. Of all specimens, genotype G1P[8] (63.3%) was the predominant strain, followed by G2P[4] (12.5%), G3P[8] (11.7%), and G9P[8] (5.1%). Uncommon strains were also detected in low percentages. We observed that the rotavirus positivity rate steadily decreased from 21% to 16% during 2008-2010, then slightly increased to 20% in 2011, when an increase in the number of G2P[4] cases was observed. Sequence and phylogenetic analysis was carried out to help understand any potential changes of G2P[4] rotaviruses over time. A number of G2P[4] strains collected between 2004 and 2011 were analyzed in detail and our analyses showed marked genetic and antigenic variability in the VP7 and VP4 genes. The Taiwanese strains could be classified into two major G2 VP7 lineages (IV and V) and two major P[4] VP4 lineages (IV and V) and several minor sublineages within lineage IV. Lineage V within both G2 and P[4] represented newly recognized genetic variants of the respective genotypes. The distribution of individual combinations of the G2 and P[4] (sub)lineages showed some temporal variations. This study provides further evidence for the great genetic diversity among G2P[4] strains and helps understand the epidemiological trends of these strains among children in Taiwan.


Anticoagulant and antiplatelet therapy choices for patients with atrial fibrillation one year after coronary stenting or acute coronary syndrome.
Guidelines recommend a combined anticoagulant and antiplatelet approach for patients with atrial fibrillation (AF) after coronary stenting (CS) or acute coronary syndrome (ACS). Finding the optimal balance of reducing ischemic risk and minimizing bleeding risk is challenging. Recent trials have evaluated a variety of regimens for up to one year for AF patients after CS/ACS. Little empiric evidence exists about the best antithrombotic strategy beyond one year. In this review two key areas are covered. First, a summary of the overall risk and benefits of anticoagulant and antiplatelet therapy in patients with AF and CS or ACS is provided. Second, despite limited empiric evidence to guide therapeutic decisions for combined anticoagulant and antiplatelet therapy in patients with AF one year after CS/ACS we provide guidance for shared patient-physician decision making. The evidence is limited. For all patients with AF and stable CAD (≥1 year after CS or ACS) the risk for thromboembolism, cardiovascular events and bleeding should be assessed individually. For patients with low bleeding risk and high risk for cardiovascular events, antiplatelet therapy might be added to anticoagulant therapy.


Serum metabolomics assessment of etiological processes predisposing ketosis in water buffalo during early lactation.
Metabolic disorders as ketosis are manifestations of the animal's inability to manage the increase in energy requirement during early lactation. Generally, buffaloes show a different response to higher metabolic demands than other ruminants with a lower incidence of metabolic problems, although ketosis is one of the major diseases that may decrease the productivity in buffaloes. The aim of this study was to characterize the metabolic profile of Mediterranean buffaloes (MB) associated with 2 different levels of β-hydroxybutyrate (BHB). Sixty-two MB within 50 days in milk (DIM) were enrolled and divided into 2 groups according to serum BHB concentration: healthy group (37 MB; BHB <0.70 mmol/L; body condition score: 5.00; parity: 3.78; and DIM: 30.70) and group at risk of hyperketonemia (25 MB; BHB ≥0.70 mmol/L; body condition score: 4.50; parity: 3.76; and DIM: 33.20). The statistical analysis was conducted by one-way ANOVA and unpaired 2-sample Wilcoxon tests. Fifty-seven metabolites were identified and among them, 12 were significant or tended to be significant. These metabolites were related to different metabolic changes such as mobilization of body resources, ruminal fermentations, urea cycle, thyroid hormone synthesis, inflammation, and oxidative stress status. These findings are suggestive of metabolic changes related to subclinical ketosis status that should be further investigated to better characterize this disease in the MB.


A comprehensive overview of promising biomarkers in stage II colorectal cancer.
Colon cancer (CC) has the highest incidence rate among gastrointestinal cancers and ranks the third in mortality among all cancers, which contributes to the current CC burden and constitutes a major public health issue. While therapeutic strategies for stage I, III, and IV CC are standardized, those for stage II CC remain debatable. The choice of adjuvant chemotherapy for patients with stage II CC depends on stage (pT4) and grade (high) of the disease, the presence of venous, perinervous, and/or lymphatic emboli, or the need of suboptimal surgery (tumor with initial occlusion or perforation needing emergency surgeries, <12 lymph nodes harvested). Several prognostic factors that have been validated in retrospective studies can potentially define a population of CC patients at low and high-risk for reccurence. The role of biomarkers is becoming increasingly important for the future personalized treatment options. We conducted a systematic overview of potential prognostic biomarkers with possible clinical implications in stage II CC.


Signalling from TPA to MAP kinase requires protein kinase C, raf and MEK: reconstitution of the signalling pathway in vitro.
The phorbol ester PMA/TPA (phorbol 12-myristate 13-acetate) is a potent tumor promoter which mimics distinct intracellular signalling events triggered by activated growth factor receptors, e.g. the activation of MAP kinases. The largest known family of TPA-binding proteins comprise members of the protein kinase C (PKC) family although other TPA-binding proteins outside the PKC family have recently been identified. In this report we addressed the mechanism and the pathway by which TPA induces the activation of MAPkinases. Using recombinant proteins and in vitro phosphorylation reactions we identified the components in the signal transduction pathway from TPA to MAPkinase and we show that the activation of MAPkinase by TPA requires the presence of protein kinase C, c-raf and the MAPkinase activator MEK. We also find that the activation of raf autophosphorylation in vitro correlates with the ability of Raf to signal to MAPkinase. Thus the activation of Raf by PKC apparently can trigger the same signalling pathway as oncogenic Raf or Raf activation by ras in combination with tyrosine phosphorylation.


A quantitative assessment of the extent and distribution of textile fibre transfer to persons involved in physical assault.
Knowledge of the number of fibres transferred during a particular activity is essential for the interpretation of findings in similar criminal cases. In this regard, violent contacts and physical assaults still present a challenge, due to a lack of robust published data. Hereby, we present the outcome of an empirical study where different assault activities were simulated by a Jiu Jitsu team and participants were asked to play either the role of an aggressive 'assailant' or a defensive 'victim', wearing cotton garments (i.e., Gi's). Four different scenarios were simulated in replicates (n = 5), each of them involving different intensity levels (low and high) and duration times (30 and 60 s). Results showed that approximately 1,000 to 44,000 fibres were cross-transferred between the participants' garments, with noticeable differences between the different scenarios. These values were significantly larger than those published in previous studies and, therefore, suggested the possibility of a current underestimation of the number of fibres transferred in physical assaults. Furthermore, statistical analysis by ANOVA indicated that the all the variables tested (i.e., intensity level, duration time, and participants role) had a significant effect on the number of transferred fibres (p < 0.001) and, consequently, that some knowledge of the case circumstances may be important to make more educated estimations. This is the first time that such a methodology has been applied for the quantitative assessment of fibre transfer between participants in assault activities. Data are expected to help practitioners with the interpretation of findings in real casework and lead to a more robust evidential assessment.


Clipping of Basilar and Middle Cerebral Artery Aneurysms: 2-dimensional operative video.
Careful preoperative planning for patients with multiple intracranial aneurysms is paramount given the importance of an appropriate trajectory and exposure for each aneurysm that will be clipped. The general principle is to clip aneurysms in a retrograde manner, such that more distal aneurysms are clipped earlier, and more superficial aneurysms are clipped later. This patient had unruptured middle cerebral artery (MCA) and basilar artery (BA) apex aneurysms and elected for surgical clipping of both lesions. An orbitozygomatic craniotomy ipsilateral to the MCA aneurysm was performed to permit clipping of both lesions. The dissection initially focused on exposure of the MCA aneurysm and then focused on the carotid-oculomotor triangle to permit basilar apex exposure and aneurysm clipping. The MCA aneurysm was clipped second. Postoperative imaging demonstrated complete obliteration of both aneurysms. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.


Rye inhibitors of animal alpha-amylases show different specificities, aggregative properties and IgE-binding capacities than their homologues from wheat and barley.
Three new members of the alpha-amylase/trypsin-inhibitor family of cereal endosperm have been isolated from rye. N-terminal amino acid sequence comparison revealed that two of the purified proteins were the rye homologues of the barley monomeric inhibitor (BMAI-1) previously described, while the other rye protein corresponded to one of the subunits of the barley and wheat heterotetrameric inhibitors. However, the inhibitory specificities (active against human salivary alpha-amylase), aggregative behaviours (mainly as dimeric forms) and IgE-binding capacities (not recognized by sera from allergic patients) of the rye inhibitors were clearly different from those of their wheat and barley counterparts. These results indicate that homologous inhibitors may have distinctive properties in different cereal species.


Younger patients and low c-peptide immunoreactivity index but not nutritional states affect fasting blood ketone levels in Japanese with type 1 diabetes after sodium-glucose cotransporter 2 inhibitor administration.
Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are available for individuals with type 1 diabetes, but appropriate use is recommended to prevent ketosis or ketoacidosis. This study aimed to evaluate the risk of ketosis in people with type 1 diabetes, focusing on the relationship between nutritional assessment, glycaemic status, c-peptide immunoreactivity (CPR) index and body composition. In total, 46 Japanese patients with type 1 diabetes were included, and dietary assessment from food photographs and ketone levels were evaluated before and after taking SGLT2is. The effect of diet on morning ketone levels was also investigated. All patients had an increase in mean ketone concentrations after taking SGLT2is (before 0.12 ± 0.06 mmol/L, after 0.23 ± 0.16 mmol/L). A significant negative correlation was found between average morning ketone levels and age (r = -0.514, p < .001) and the CPR index (r = -0.523, p = .038) after taking SGLT2is. Using a mixed-effects model based on the results before starting the inhibitors, it was noted that both patient-to-patient and age, or patient-to-patient and capacity of insulin secretion, influenced the ketone levels. Multiple regression analysis showed that factors associated with the risk of increasing ketone levels after taking SGLT2is were younger age (β = -0.504, p = .003) and a low ratio of basal to bolus insulin (β = -0.420, p = .005). When administering SGLT2is to patients with a low CPR index or younger patients with type 1 diabetes, adequate instructions to prevent ketosis should be given.


Expression of Rhizobium meliloti symbiotic promoters in Azorhizobium caulinodans.
Plasmids containing Rhizobium meliloti symbiotic promoters P1 (promoter of nifHDK) and P2 (promoter of fixABCX) when mobilized into the cells of Azorhizobium caulinodans strain IRBG 46 showed strong expression of these promoters under free-living microaerobic as well as symbiotic conditions. Under free-living conditions microaerobiosis (3% or less O2) was found to be sufficient to activate these promoters; expression being higher at 1% than at 3% O2 concentration. Under symbiotic conditions the expression was much more stronger-with bacteroids in stem nodules showing higher expression than those in root nodules. Under both the conditions expression of the promoters in the native R. meliloti strain Rm102F34 was lower than that in the A. caulinodans strain IRBG 46. The results suggest a functional homology of these promoters in the heterologous background of A. caulinodans.


Ring chromosome 15: phenotype, Ag-NOR analysis, secondary aneuploidy, and associated chromosome instability.
Cytogenetic analysis of a 15 month old girl evaluated for severe developmental delay and acral skeletal hypoplasia revealed a predominant 46,XX,r(15) karyotype. Prophase banding analysis showed minimal deletion of the ring chromosome (breakpoints p12 and q26), while silver staining showed it to have an active nucleolus organizing region, multiple abnormal secondary configurations, and decreased satellite association. Although there was no spontaneous instability in the rest of the karyotype, gentian violet-induced chromosome breakage was significantly increased. The rate of spontaneous sister chromatid exchange was not elevated. Cellular mosaicism for chromosome 15 aneuploidy most likely accounts for the patient's phenotypic abnormalities.


Monoterpene glycosides from Paeonia veitchii.
The EtOH extract of the roots of Paeonia veitchii afforded two new monoterpene glycosides paeonidanin I (1) and paeonidanin J (2), and a new dimeric monoterpene glycoside paeonidanin K (3). Their structures were elucidated on the basis of spectroscopic means and hydrolysis products.


LIVIVO - the Vertical Search Engine for Life Sciences.
The explosive growth of literature and data in the life sciences challenges researchers to keep track of current advancements in their disciplines. Novel approaches in the life science like the One Health paradigm require integrated methodologies in order to link and connect heterogeneous information from databases and literature resources. Current publications in the life sciences are increasingly characterized by the employment of trans-disciplinary methodologies comprising molecular and cell biology, genetics, genomic, epigenomic, transcriptional and proteomic high throughput technologies with data from humans, plants, and animals. The literature search engine LIVIVO empowers retrieval functionality by incorporating various literature resources from medicine, health, environment, agriculture and nutrition. LIVIVO is developed in-house by ZB MED - Information Centre for Life Sciences. It provides a user-friendly and usability-tested search interface with a corpus of 55 Million citations derived from 50 databases. Standardized application programming interfaces are available for data export and high throughput retrieval. The search functions allow for semantic retrieval with filtering options based on life science entities. The service oriented architecture of LIVIVO uses four different implementation layers to deliver search services. A Knowledge Environment is developed by ZB MED to deal with the heterogeneity of data as an integrative approach to model, store, and link semantic concepts within literature resources and databases. Future work will focus on the exploitation of life science ontologies and on the employment of NLP technologies in order to improve query expansion, filters in faceted search, and concept based relevancy rankings in LIVIVO.


Replication-defective Friend murine leukemia virus particles containing uncleaved gag polyproteins and decreased levels of envelope glycoprotein.
An erythroleukemia cell clone, 7C, which failed to produce reverse transcriptase-containing virions or infectious virus, was found to produce noninfectious virus particles by gradient banding of [3H]leucine- and [3H]uridine-labeled virions. The RNA from the 7C virus was shown to consist of the normal 70S size component, which converted to 35S upon heat denaturation. In contrast, the 7C virion proteins showed multiple defects. Analysis of the virion proteins by gel electrophoresis demonstrated that the pr65 gag precursor was incorporated into the 7C virus and that the processing of this precursor was severely diminished. Polymerase proteins pr180gag-pol and pr120pol were also detected in virions, and a third possible polymerase protein, p70, was reduced in size compared to its normal counterpart, p80. Incorporation of the viral gp70 glycoprotein into particles was also reduced 10-fold, despite synthesis and incorporation of gp70 into the 7C cell membrane in normal amounts. Pulse-chase analysis of the synthesis of the viral gag and env proteins in 7C cells showed greatly reduced amounts of pr180gag-pol, pr65gag, p80gag, and p42gag, whereas pr90env, gp70, and spleen focus-forming virus-specific gp55 were synthesized and processed normally. These results suggested that at least one defect in 7C virus was impaired cleavage of gag or pol proteins or both, most likely due to a lack of the appropriate viral protease, and that this lack of cleavage might affect incorporation of gp70 into virus particles.


Scripture, history, and authority in a Christian view of abortion: a response to Paul Simmons.
In this reply to Paul Simmons, it is argued that while biblical scripture should be understood as the Christian's first and final authority, it is appropriate to draw on other writings as sources for moral reflection. Responsible biblical interpretation and theological reflection must include careful historical analysis. It is inaccurate and anachronistic to read into early Jewish and Christian thinkers a position much like the reigning secular philosophical-legal position on abortion, where fetal non-personhood and individual freedom results in abortion without legal constraints. Careful scholarship reveals that a theological community-based Christian ethic, which develops from first century reflections and biblical canonical authority, prohibits direct abortion as an option for the Christian community.


FDA Approval Summary: Ruxolitinib for Treatment of Chronic Graft-Versus-Host Disease after Failure of One or Two Lines of Systemic Therapy.
On September 22, 2021, the Food and Drug Administration approved ruxolitinib for the treatment of chronic graft-versus-host disease (cGVHD) after the failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older. Approval was based on Study INCB 18424-365 (REACH-3; CINC424D2301; NCT03112603), a randomized, open-label, multicenter trial of ruxolitinib in comparison to best available therapy (BAT) for the treatment of corticosteroid-refractory cGVHD occurring after the allogeneic hematopoietic stem cell transplantation. A total of 329 patients were randomized 1:1 to receive either ruxolitinib 10 mg twice daily (n = 165) or BAT (n = 164). BAT was selected by the investigator prior to randomization. The overall response rate through Cycle 7 Day 1 was 70% (95% CI, 63-77) in the ruxolitinib arm, and 57% (95% CI, 49-65) in the BAT arm. The median duration of response, calculated from first response to progression, death, or initiation of new systemic therapies for cGVHD, was 4.2 months (95% CI, 3.2-6.7) for the ruxolitinib arm and 2.1 months (95% CI, 1.6-3.2) for the BAT arm; and the median time from first response to death or initiation of new systemic therapies for cGVHD was 25 months (95% CI, 16.8-not estimable) for the ruxolitinib arm and 5.6 months (95% CI, 4.1-7.8) for the BAT arm. Common adverse reactions included anemia, thrombocytopenia, and infections. Given the observed response rate with durability, the clinical benefit of ruxolitinib appears to outweigh the risks of treatment for cGVHD after the failure of one or two lines of systemic therapy.


Alkyltributylphosphonium chloride ionic liquids: synthesis, physicochemical properties and crystal structure.
A series of alkyltributylphosphonium chloride ionic liquids, prepared from tributylphosphine and the respective 1-chloroalkane, C(n)H(2n+1)Cl (where n = 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 or 14), is reported. This work is a continuation of an extended series of tetraalkylphosphonium ionic liquids, where the focus is on the variability of n and its impact on the physical properties, such as melting points/glass transitions, thermal stability, density and viscosity. Experimental density and viscosity data were interpreted using QPSR and group contribution methods and the crystal structure of propyl(tributyl)phosphonium chloride is detailed.


[Renal angiomyolipoma rupture during pregnancy].
A 40 year-old 2nd gesta pregnant woman (34.5 weeks of amenorhea) was admitted to hospital for abdominal pain and arterial hypotension which were rapidly related to a retroperitoneal haematoma due to left kidney bleeding. Emergency cesarean delivery under general anaesthesia was undertaken because of foetal distress. Exploration of the retroperitonal space after foetal extraction confirmed the presence of a large haematoma and abnormal left renal morphology. The retroperitoneal space was drained without any further intervention. Subsequently, abdominal and thoracic computerised tomographic examination showed bilateral dysplasia of the kidneys and pulmonary cysts consistent with the diagnosis of renal angiomyolipoma and pulmonary lymphangioleiomyomatosis. The case report is of interest because of the circumstances of discovery of the disease and because nephrectomy was not necessary to control the bleeding of the left kidney. Six months after the incident the patient and the child are in good condition.


Exact multipoint and multitime correlation functions of a one-dimensional model of adsorption and evaporation of dimers.
In this work, we provide a method that allows us to compute exactly the multipoint and multitime correlation functions of a one-dimensional stochastic model of dimer adsorption evaporation with random (uncorrelated) initial states. In particular, explicit expressions of the two-point non-instantaneous/instantaneous correlation functions are obtained. The long-time behavior of these expressions is discussed in detail and in various physical regimes.


Surgical management of a retro-rectal cystic hamartoma (tailgut cyst) using a trans-rectal approach: a case report and review of the literature.
Retro-rectal cystic hamartoma (tailgut cyst) is a rare congenital developmental lesion arising from post-natal primitive gut remnants in the retro-rectal space. The rarity of the lesion and its anatomical position usually leads to difficulty in diagnosis and surgical management. Complete surgical resection remains the cornerstone of treatment. A dozen or so surgical approaches have been described in the literature to date to make the operation as simple as possible, but the trans-rectal access route is extremely rarely reported and not well described. Here, we present a case that demonstrates the trans-rectal approach to a retro-rectal tumor is a feasible option in terms of surgical radicality, minimal invasiveness and safety for carefully selected patients with this rare type of retro-rectal cystic lesion. A 29-year-old Caucasian woman was referred to our institution due to perineal pain extending to the right inguinal region. Her symptoms had been present for the last two months. She was first examined at her regional hospital for a suspected ruptured ovarian cyst; however, after consultation with a gynecologist and a computed tomography scan of her pelvis, a tumor in the retro-rectal space was discovered. Our patient was admitted to our hospital and when a pelvic magnetic resonance imaging study confirmed the diagnosis of the retro-rectal cystic formation, a complete extirpation of retro-rectal tumor fixed to the coccyx using trans-rectal approach was performed. The final pathological diagnosis was retro-rectal cystic hamartoma (tailgut cyst) with no evidence of malignancy. Her post-operative course was uneventful, and at four months after surgery our patient is symptom free with no evidence of recurrent or residual disease. Trans-rectal excision is feasible in terms of surgical radicality and is a simple to perform, minimally invasive and safe option, providing complete recovery for carefully selected patients with retro-rectal cystic hamartoma treated operatively.


Greglist: a database listing potential G-quadruplex regulated genes.
The double helix is a conformation that genomic DNA usually assumes; under certain conditions, however, guanine-rich DNA sequences can form a four-stranded structure, G-quadruplex, which is found to play a role in regulating gene expression. Indeed, it has been demonstrated that the G-quadruplex formed in the c-MYC promoter suppresses its transcriptional activity. Recent studies suggest that G-quadruplex motifs (GQMs) are enriched in human gene promoters. To facilitate the research of G-quadruplex, we have constructed Greglist, a database listing potentially G-quadruplex regulated genes. Greglist harbors genes that contain promoter GQMs from genomes of various species, including humans, mice, rats and chickens. Many important genes are found to contain previously unreported promoter GQMs, such as ATM, BAD, AKT1, LEPR, UCP1, APOE, DKK1, WT1, WEE1, WNT1 and CLOCK. Furthermore, we find that not only protein coding genes, 126 human microRNAs also contain promoter GQMs. Greglist therefore provides candidates for further studying G-quadruplex functions and is freely available at http://tubic.tju.edu.cn/greglist.