Heterologous expression of the CYP51 gene of the obligate fungus Blumeria graminis in the necrotrophic fungus Botrytis cinerea.
As it is extremely difficult to make DNA transformation for the obligate fungus, Blumeria graminis f. sp. tritici (Bgt), we developed a heterologous expression system for characterization of a Bgt gene, CYP51, which encodes 14α-demethylase. The CYP51 gene from Bgt was transformed into the necrotrophic fungus, Botrytis cinerea. Reverse transcription polymerase chain reaction showed that the Bgt CYP51 was transcribed in B. cinerea. Green fluorescence was observed in the transformants of B. cinerea carrying the Bgt CYP51-GFP fusion cassette, suggesting that its translation was successful. Fungicide sensitivity tests revealed that B. cinerea transformed with Bgt CYP51 showed reduced sensitivity to a sterol demethylation inhibitor triadimefon, but not to a benzimidazole fungicide carbendazim. These results indicated that this heterologous expression system can be used for functional analysis of other Bgt genes.


Extrapulmonary tuberculosis in Lady Reading Hospital Peshawar, NWFP, Pakistan: survey of biopsy results.
Tuberculosis is a disease of poor countries. In the recent years, there has been an increase in the occurrence of extra-pulmonary tuberculosis (EPTB) world over. As very little data is available regarding the situation of EPTB in NWFP, this study was conducted to asses its frequency in various organ systems of the body and to evaluate the role of demographic factors like sex and age in its causation. A total of 525 cases of EPTB diagnosed histopathologically in the Department of Pathology, Lady Reading Hospital Peshawar in the years 2002-2005 were included in the study. Age, sex and sites of biopsies were recorded. High female preponderance was noted with a M:F ratio of 1:2. Mean age was 35 years and 70% of the patients were in the age group 15-45 years. Lymph nodes were the most common site of EPTB, involved in 66.4% of the cases. EPTB has high rates in females in their reproductive age. Tuberculous lymphadenitis is the most common form of EPTB. High occurrence of EPTB in female population needs immediate attention of tuberculosis control programs.


Effects of an Extensively Hydrolyzed Formula Supplemented with Two Human Milk Oligosaccharides on Growth, Tolerability, Safety and Infection Risk in Infants with Cow's Milk Protein Allergy: A Randomized, Multi-Center Trial.
This randomized clinical trial (Registration: NCT03085134) assessed if an extensively hydrolyzed formula (EHF) supplemented with two human milk oligosaccharides (HMO) and reduced protein content (2.20 g/100 kcal) supports normal growth in infants with cow's milk protein allergy (CMPA). Secondary outcomes were gastrointestinal tolerability, safety, and effect on infections. Nonbreastfed infants aged 0−6 months with CMPA were enrolled. Body weight, length, and head circumference were measured monthly for 4 months (primary study endpoint), after 6 months, and at the age of 12 months. Of 200 infants screened, 194 (mean age 3.2 months) were randomized. At the 4-month follow-up, daily weight gain for the test formula was noninferior to the control formula; p < 0.005. There were no significant group differences in anthropometric parameters. Both formulas were safe and well tolerated. Infants in the HMO group had a statistically significant reduction in the frequency of upper respiratory tract infections and a lower incidence of ear infections at 12 months (per protocol analysis). The relative risk of lower respiratory tract and gastrointestinal infections was reduced by 30−40%, but this was not statistically significant due to sample size limitations. In summary, the HMO-supplemented formula supports normal growth in infants with CMPA and suggests a protective effect against respiratory and ear infections in the first year of life.


Endoscopic clipping of a middle cerebral artery aneurysm in a middle fossa arachnoid cyst and review of the literature.
Arachnoid cysts are often associated with subdural hematoma following head trauma. The incidental finding of an aneurysma and a cyst is rare. We describe for the first time the treatment of such a case using endoscopic techniques. A 44-year-old man was admitted to our hospital with a mild headache and a hemifacial spasm attack at the right side of his face. The radiological examinations demonstrated bilateral slyvian fissure arachnoid cysts and an aneurysm with the dome projecting superolaterally, at the bifurcation of the right middle cerebral artery in the arachnoid cyst. The patient underwent a complete endoscopic surgical clipping of the aneurysm, and partial excision of the right cyst wall and bilateral fenestration to the basal cistern via a single burr-hole craniectomy at the right temporal region. The patient had an uneventful postoperative course without neurological impairment and complication. However, his complaints still persisted postoperatively. Endoscopic management of arachnoid cysts is an effective and less morbid treatment. This less invasive option might be safe for the clipping of aneurysms within an arachnoid cyst with no additional morbidity for the patient. With smaller operative exposures and yet better visualization offered, neuroendoscopy may reduce operative morbidity.


Quality of informal care for persons with dementia: dimensions and correlates.
The majority of persons with dementia live in the community where most of their care is provided by family members. We aimed to expand our limited knowledge about the styles of high-quality care, such as person-centered care, and poor-quality care adopted by these informal caregivers and the characteristics of those who provide better care. We conducted a mail survey of 148 family caregivers. Caregiving styles were measured with items from existing scales that had not been analyzed together before. Factor analysis of these items was used to identify styles of caregiving, and structural equation modeling was used to identify their relationships with caregiver and care-recipient characteristics. Three high quality-of-care factors (personalized, respectful, and compensatory) and three poor quality-of-care factors (punitive, controlling, and withdrawing) were found. The personality traits of agreeableness, openness, conscientiousness, and neuroticism were related to higher quality of care, and the trait of extraversion was related to poorer quality of care. Wishful coping - an avoidance/escape strategy - was linked to poorer quality of care. We discovered new dimensions of quality of care, some consistent with person-centered care and some antithetical to this model, and we identified for the first time caregiver personality traits and coping strategies associated with better quality of care. These results may be useful in targeting caregiver interventions to benefit both caregivers and care recipients.


Development and validation of a liquid chromatographic method for fexofenadine hydrochloride in capsules.
This paper describes the development and validation of a new, simple, fast, and sensitive liquid chromatographic method for the determination of the antihistamine fexofenadine. Although widely used in the treatment of allergic diseases, fexofenadine is not listed in any pharmacopeia, and there are few methods in the literature for its quantitation in pharmaceutical dosage forms. In this work, a LiChrospher 100 RP-18 (250 x 4.0 mm, 5 microm) column was used as the stationary phase, and acetonitrile-5mM ammonium acetate buffer (50 + 50, v/v) at pH 3.2 was the mobile phase. Through the evaluation of the analytical parameters, it was shown that the method is linear (r = 0.9999) at concentrations ranging from 20.0 to 80.0 microg/mL, precise (intraday relative standard deviation [RSD] values = 0.85, 0.40, and 0.81%; interday RSD = 0.77%), accurate (mean recovery = 99.05%), specific, and robust. The detection and quantitation limits are 0.3409 and 1.033 microg/mL, respectively. These low values show the good sensitivity of the proposed method.


Income distribution trends and future food demand.
This paper surveys the theoretical literature on the relationship between income distribution and food demand, and identifies main gaps of current food modelling techniques that affect the accuracy of food demand projections. At the heart of the relationship between income distribution and food demand is Engel's law. Engel's law establishes that as income increases, households' demand for food increases less than proportionally. A consequence of this law is that the particular shape of the distribution of income across individuals and countries affects the rate of growth of food demand. Our review of the literature suggests that existing models of food demand fail to incorporate the required Engel flexibility when (i) aggregating different food budget shares among households; and (ii) changing budget shares as income grows. We perform simple simulations to predict growth in food demand under alternative income distribution scenarios taking into account nonlinearity of food demand. Results suggest that (i) distributional effects are to be expected from changes in between-countries inequality, rather than within-country inequality; and (ii) simulations of an optimistic and a pessimistic scenario of income inequality suggest that world food demand in 2050 would be 2.7 per cent higher and 5.4 per cent lower than distributional-neutral growth, respectively.


A Social Identity Approach to Understanding Responses to Child Sexual Abuse Allegations.
Two studies investigated the role of group allegiances in contributing to the failure of institutions to appropriately respond to allegations of child sexual abuse. In Study 1, 601 participants read a news article detailing an allegation of child sexual abuse against a Catholic Priest. Catholics were more protective of the accused-and more skeptical of the accuser-than other participants, an effect that was particularly pronounced among strongly identified Catholics. In Study 2 (N = 404), the tendency for Catholics to be more protective of the accused and more skeptical of the accuser than non-Catholics was replicated. Moreover, these effects held independently of the objective likelihood that the accused was guilty. Overall, the data show that group loyalties provide a psychological motivation to disbelieve child abuse allegations. Furthermore, the people for whom this motivation is strongest are also the people who are most likely to be responsible for receiving and investigating allegations: highly identified ingroup members. The findings highlight the psychological mechanisms that may limit the ability of senior Church figures to conduct impartial investigations into allegations of child abuse within the Church.


Pelvic-Floor Properties in Women Reporting Urinary Incontinence After Surgery and Radiotherapy for Endometrial Cancer.
Endometrial cancer is the fourth most prevalent cancer in Canadian women. Radiotherapy (RT) is frequently recommended as an adjuvant treatment. There is a high prevalence (>80%) of urinary incontinence (UI) after RT. It is plausible that UI is associated, at least in part, with alterations of the pelvic-floor muscles (PFM). The aim of this exploratory study was to compare the PFM functional properties of women reporting UI after hysterectomy and RT for endometrial cancer with those of women with a history of hysterectomy but without UI. A descriptive cross-sectional study was conducted. Eleven women were recruited for the affected group, and 18 were recruited for the comparison group. Urogenital and bowel functions were assessed using International Consultation on Incontinence Questionnaires, and PFM properties were evaluated using a Montreal dynamometer. Nonparametric tests were used for comparison of personal characteristics, functional status, and muscle properties. A correspondence analysis detailed the association between UI severity and PFM properties. Maximal opening of dynamometer branches, maximal vaginal length, PFM maximum force and rate of force development in a strength test, and number of rapid contractions during a speed test were reduced in the affected group. No significant difference was found for the endurance test. The severity of UI was found to correspond to the rate of force development and the number of rapid contractions in a speed test, endurance, age, and vaginal length. The results are limited to the population studied. The small sample size limited the strength of the conclusions. Some evidence of alterations in PFM properties were found in women with UI after hysterectomy and RT for endometrial cancer. These alterations appeared to be associated with UI, suggesting a possible role for rehabilitation.


17(E)-picolinylidene androstane derivatives as potential inhibitors of prostate cancer cell growth: antiproliferative activity and molecular docking studies.
We report a rapid and efficient synthesis of A-ring modified 17α-picolyl and 17(E)-picolinylidene androstane derivatives from dehydroepiandrosterone. Compounds were validated spectroscopically and structurally characterized by X-ray crystallography. Virtual screening by molecular docking against clinical targets of steroidal anticancer drugs (ERα, AR, Aromatase and CYP17A1) suggests that 17(E)-picolinylidene, but not 17α-picolyl androstanes could specifically interact with CYP17A1 (17α-hydroxylase) with similar geometry and affinity as Abiraterone, a 17-pyridinyl androstane drug clinically used in the treatment of prostate cancer. In addition, several 17(E)-picolinylidene androstanes demonstrated selective antiproliferative activity against PC3 prostate cancer cells, which correlates with Abiraterone antiproliferative activity and predicted CYP17A1 binding affinities. Based on these preliminary results, 17(E)-picolinylidene androstane derivatives could be a promising starting point for the development of new compounds for the treatment of prostate cancer.


Induction of cell fusion/apoptosis in anaplastic thyroid carcinoma in orthotopic mouse model by urokinase-specific oncolytic Sendai virus.
This study was designed to assess the therapeutic effect of urokinase-targeted recombinant oncolytic Sendai virus, termed "BioKnife," on anaplastic thyroid carcinoma (ATC). Urokinase activity was investigated in human ATC cell lines, and BioKnife cytotoxicity against the cell lines was evaluated in vitro. Orthotopic mouse models of ATC were treated with three intratumoral injections of BioKnife, control virus, or phosphate-buffered saline (PBS) and were observed daily until >20% weight loss occurred. All three ATC cell lines showed a high level of urokinase activity. BioKnife induced urokinase-dependent cell fusion and cytotoxicity in all cell lines. Orthotopic models treated with BioKnife showed significantly prolonged survival compared with models treated with control virus or PBS (BioKnife 41.6 ± 15.0, control virus 17.0 ± 2.9, PBS 17.7 ± 6.3 days). BioKnife exerted therapeutic effects in orthotopic ATC mouse models. Thus, BioKnife represents a possible treatment option for ATC.


Is natural background or radiation from nuclear power plants leukemogenic?
In view of the enormous number of base pair replications per annum in hemopoietic stem cells with the likelihood of coding errors, the rarity of the leukemogenic event at the cellular level after high doses of radiation, the infrequent occurrence of radiation events in cells at low-level exposure (large fraction of cells uninvolved), biological protective mechanisms and the realization that exposure of human populations to radiation from nuclear power plants is a very small fraction of natural radioactivity and will for the foreseeable future remain small and that populations exposed to high natural background radiation show no detectable harmful effects, it is concluded that either there is no effect, or for statistical reasons one cannot detect an effect.


Light propagation in a Penrose unilluminable room.
Using the finite-difference time-domain method, propagation of light waves is studied in a Penrose unilluminable room. Such a room always has dark (unilluminated) regions, regardless of the position of a point source in it. However, in contrast to the predictions of ray dynamical simulations, a small amount of light propagates into the unilluminated regions via diffraction. We conjecture that this diffraction effect becomes more prominent as the size of the room decreases.


Molecular carcinogenesis of squamous cell carcinomas of the skin.
Squamous cell carcinomas (SCCs) of the skin were suggested to develop through a multistep process that involves activation of proto-oncogenes and/or inactivation of tumor suppressor genes in the human skin keratinocytes. Exposure to ultra-violet (UV), especially UV-B, radiation is the most common cause for these genetic abnormalities in cells. We review causation of SCCs and genetic abnormalities in human SCCs with the current work. To elucidate the multistep process, we developed a method for examining the combinatorial function in vivo of plural genes in human keratinocytes. Using high efficiency retroviral transductions, we could express plural genes serially in normal human primary keratinocytes and use these cells to regenerate human skin on SCID mice. A combinatorial transduction of H-RasV12 and cyclin dependent kinase 4 (CDK4) produced human epidermal neoplasia resembling SCC. These findings were consistent with our previous results of mutation analysis in SCCs, one of which had both mutations of H-Ras gene and the INK4a locus. Therefore, it is suggested that a combination of these genetic abnormalities might be crucial to the carcinogenesis at least in a subset of SCCs.


A hotspot of spontaneous and UV-induced illegitimate recombination during formation of lambda bio transducing phage.
To study the mechanism of spontaneous and UV-induced illegitimate recombination, we examined the formation of the lambda bio specialized transducing phage in Escherichia coli. Because most lambda bio transducing phages have double defects in the red and gam genes and have the capacity to form a plaque on an E. coli P2 lysogen (Spi- phenotype), we selected lambda bio transducing phage by their Spi- phenotype, rather than using the bio marker. We determined sequences of recombination junctions of lambda bio transducing phages isolated with or without UV irradiation and deduced sequences of parental recombination sites. The recombination sites were widely distributed on E. coli bio and lambda DNAs, except for a hotspot which accounts for 57% of UV-induced lambda bio transducing phages and 77% of spontaneously induced lambda bio transducing phages. The hotspot sites on E. coli and lambda DNAs shared a short homology of 9 bp. In addition, we detected direct repeat sequences of 8 bp within and near both the bio and lambda hotspots. A recA mutation did not affect the frequency of the recombination at the hotspot, indicating that this recombination is not a variant of recA-dependent homologous recombination. We discuss a model in which the short homology as well as the direct repeats play essential roles in illegitimate recombination at the hotspot.


Anaphylaxis after ingestion of carmine colored foods: two case reports and a review of the literature.
Two patients with adverse food reactions to foods colored with carmine dye are presented, along with a review of the medical literature addressing adverse reactions to carmine colorant. This review summarizes the mounting evidence suggesting that adverse reactions to carmine colorant are the result of an IgE mediated mechanism.


Poly (I:C) and imiquimod induced immune responses and their effects on the survival of olive flounder (Paralichthys olivaceus) from viral haemorrhagic septicaemia.
The stimulation of immune genes by polyinosinic:polycytidylic acid (poly (I:C)) and imiquimod in olive flounder (Paralichthys olivaceus) and their role in control of viral haemorrhagic septicaemia virus (VHSV) infection were examined. Poly (I:C) (100 μg/fish) treated olive flounder had very low mortality (5%) post VHSV infection, while the imiquimod treated group had 65% and 85% mortality at a dose of 100 μg/fish and 50 μg/fish, respectively. Though the imiquimod treated group had high mortality, it was lower than the untreated group, which had 90% mortality. In vivo experiments were conducted to determine effect of the two ligands on immune modulation in the head kidney of olive flounder. Poly (I:C) activated the immune genes (TLR-3, TLR-7, MDA-5, LGP-2, IRF-3, IRF-7, IL-1β type I IFN and Mx) very early, within 1 d post stimulation, faster and stronger than imiquimod. Though Mx levels were enhanced by imiquimod, the host was still susceptible to VHSV. The poly (I:C) treated group had a high immune response at the time of infection and 1 dpi, though it decreased at later stages. The imiquimod treated group and the unstimulated group had a higher immune response to VHSV compared to the poly (I:C) treated group. The nucleoprotein copies of VHSV were very low in the poly (I:C) treated group but interestingly, were high in both untreated and imiquimod treated fish. Thus, host survival from a viral infection does not only depend on the quantity of immune response but also the time of response. Although imiquimod enhanced immune gene expression in olive flounder, a delayed response could be the reason for high mortality to VHS compared with poly (I:C), which induced the immune system effectively and efficiently to protect the host.


Inducible defense against pathogens and parasites: optimal choice among multiple options.
Defense against pathogen, parasites and herbivores is often enhanced after their invasion into the host's body. Sometimes different options are adopted depending on the identity and the quantity of the pathogen, exemplified by the switch between Th1 and Th2 systems in mammalian immunity. In this paper, we study the optimal defense of the host when two alternative responses are available, which differ in the effectiveness of suppressing the growth of pathogen (parasite, or herbivore), the damage to the host caused by the defense response, and the magnitude of time delay before the defense response becomes fully effective. The optimal defense is the one that minimizes the sum of the damages caused by the pathogen and the cost due to defense activities. The damage by pathogens increases in proportion to the time integral of the pathogen abundance, and the cost is proportional to the defense activity. We can prove that a single globally optimal combination of defense options always exists and there is no other local optimum. Depending on the parameters, the optimal is to adopt only the early response, only the late response, or both responses. The defense response with a shorter time delay is more heavily used when the pathogen grows fast, the initial pathogen abundance is large, and the difference in time delay is long. We also study the host's optimal choice between constitutive and inducible defenses. In the constitutive defense, the response to pathogen attack works without delay, but it causes the cost even when the pathogen attack does not occur. We discuss mammalian immunity and the plant chemical defense from the model's viewpoint.


Surgical approach and outcome in torsion of testis.
A total of 31 patients with acute torsion treated over a fifteen-year period are reviewed. The peak incidence of the disease, its seasonal variations, predisposing factors, surgical procedure, and clinical outcome are analyzed. Most of the patients were operated upon via an inguinal incision and underwent detorsion and fixation or untwisting only of the involved testis. The contralateral one was never anchored. All patients were asked to complete a questionnaire, with 2 of 3 responding from one to fifteen years (mean, 6.7 years) after surgery. None underwent recurrent surgery on either testicle. We conclude that fixation of the testes, both detorsioned and normal is not necessary.


Phytoextraction of metals from a multiply contaminated soil by Indian mustard.
The effects of nitrilotriacetate (NTA) and citric acid applications on metal extractability from a multiply metal-contaminated soil, as well as on their uptake and accumulation by Indian mustard (Brassica juncea) were investigated. Desorption of metals from the soil increased with chelate concentration, NTA being more effective than citric acid in solubilising the metals. Plants were grown in a sandy soil collected from a contaminated field site and polluted by Cd, Cr, Cu, Pb and Zn. After 43 days of plant growth, pots were amended with NTA or citric acid at 5 mmol kg-1 soil. Control pots were not treated with any chelate. Harvest of plants was performed 1 week after chelate addition. Soil water-, NH4NO3- and DTPA-extractable Cd, Cu, Pb and Zn fractions were enhanced only in the presence of NTA. In comparison to unamended plants, Indian mustard shoot dry weights suffered significant reductions following NTA application. NTA treatment increased shoot metal concentrations by a factor of 2-3, whereas citric acid did not induce any difference compared to the control. Chromium was detected in the above-ground tissues only after NTA amendment. Due to differences in dry matter yield, a significant enhancement of metal uptake was observed in NTA-treated plants for Cu and Zn.


Immunomodulatory therapy associated to anti-parasite drugs as a way to prevent severe forms of malaria.
Malaria is an important problem of public health. It is estimated that 350 to 500 million clinical cases occur annually, which cause 1.1 and 1.3 million deaths every year. The excessive activation of the immune system plays an important role in the pathogenesis of the disease. The cells of the immune system of Plasmodium-infected individuals not only produce large amounts of cytokines, which have anti-parasite effects, but also participate in the pathogenesis of the severe complications of malaria. A central feature of P. falciparum infection is the sequestration of parasitized erythrocytes within the small vessels of major organs. This involves molecular interactions between antigens of parasitized erythrocytes and host receptors, expressed on the surface of endothelial cells. The increased production of pro-inflammatory cytokines and nitric oxide, followed by the up regulation of endothelial cell adhesion molecules, influences the progression of cerebral lesions. The association of drugs capable of modulating the immune response to anti plasmodial drugs has been evaluated. Antibodies to tumor necrosis factor, pentoxifylline, and thalidomide have been tried for this purpose with variable success. This review submitted this subject to a critical assessment and suggests ways to take advantage of immunomodulatory drugs, associated to anti parasite therapy, to reduce the morbimortality of malaria.


Characterization of the Catania VIS for H2(+).
The Catania VIS 2.46 GHz source has been installed on a test stand at the Best Cyclotron Systems, in Vancouver, Canada, as part of the DAEδALUS and IsoDAR R&D program. Studies to date include optimization for H2 (+)/p ratio and emittance measurements. Inflection, capture, and acceleration tests will be conducted when a small test cyclotron is completed.


Comparison of carbon dioxide and argon euthanasia: effects on behavior, heart rate, and respiratory lesions in rats.
In this study we compared rat (n = 16) responses to euthanasia with either gradual-fill CO(2) or rapid induction argon gas by evaluating the animals' heart rate via radiotelemetry, behavior, and vocalizations. We also evaluated the histologic effects of the gases. Rats were placed in an open test chamber 24 h before the start of the experiment. During baseline tests, rats were exposed to oxygen to evaluate the effects of the noise and movement of gas entering the chamber; 1 wk later, rats were euthanized by gas displacement with either 10%/min CO(2) or 50%/min argon gas. Rats tended to have higher heart rats and were more active during the baseline test, but these parameters were normal before the euthanasia experiment, suggesting that the rats had acclimated to the equipment. Heart rate, behavior, and ultrasonic vocalizations were recorded for 2 min after gas introduction in both groups. All rats appeared conscious throughout the test interval. The heart rates of rats exposed to argon did not change, whereas those of rats exposed to CO(2) declined significantly. Unlike those exposed to CO(2), rats euthanized with argon gas gasped and demonstrated seizure-like activity. There were no differences in the pulmonary lesions resulting from death by either gas. Our results suggest that argon as a sole euthanasia agent is aversive to rats. CO(2) using a 10%/min displacement may be less aversive than more rapid displacements. Future research investigating methods of euthanasia should allow sufficient time for the rats to acclimate to the test apparatus.


A regional analysis of illegal aliens.
"This paper combines inferences about the unknown population of illegal aliens with apprehension data and economic indicators to estimate the separate effects of enforcement activity and economic changes on the stock of illegal aliens in the United States. This method offers a substantial improvement over previous empirical estimates based solely on apprehension data."


Evidences of self planting propagules of Rhizophora mangle L.
The authors of the 19th century had demonstrated the viviparity of the species Rhizophora mangle L. with the formation of propagules in the form of spears devoid a radicle, adapted self-planting in the soil of the mangrove or to leave floating in vertical during the high tide. With low tide the propagules self-planting or remain prostrate on the soil but later become upright later. When the seedlings are unearthed, those who are self-planting are straight from end to end; those that stood erect later show a curvature at the base in the form of J (J-shaped). Authors of the last 30 years have questioned the self-planting and accurately demonstrate how the prostrate propagules rise from the ground. It has been verified that the propagule is stem from end to end and does not present radicle, that is, under the plumale there is the hypocotyls without a root. All roots are adventitious, agreeing with 19th century researchers, not lateral roots as researchers of the present century have claimed. Propagules that return to the beach in Porto Seguro (BA) probably of another flowering period show an extra growth of the lower part, but this growth remains a stem rather than a root, demonstrating that there is no root, as 19th century researchers claimed.


An RNAi screen for genes that affect nuclear morphology in Caenorhabditis elegans reveals the involvement of unexpected processes.
Aberration in nuclear morphology is one of the hallmarks of cellular transformation. However, the processes that, when mis-regulated, result aberrant nuclear morphology are poorly understood. In this study, we carried out a systematic, high-throughput RNAi screen for genes that affect nuclear morphology in Caenorhabditis elegans embryos. The screen employed over 1700 RNAi constructs against genes required for embryonic viability. Nuclei of early embryos are typically spherical, and their NPCs are evenly distributed. The screen was performed on early embryos expressing a fluorescently tagged component of the nuclear pore complex (NPC), allowing visualization of nuclear shape as well as the distribution of NPCs around the nuclear envelope. Our screen uncovered 182 genes whose downregulation resulted in one or more abnormal nuclear phenotypes, including multiple nuclei, micronuclei, abnormal nuclear shape, anaphase bridges, and abnormal NPC distribution. Many of these genes fall into common functional groups, including some that were not previously known to affect nuclear morphology, such as genes involved in mitochondrial function, the vacuolar ATPase, and the CCT chaperonin complex. The results of this screen add to our growing knowledge of processes that affect nuclear morphology and that may be altered in cancer cells that exhibit abnormal nuclear shape.


Combining diclofenac with acetaminophen or acetaminophen-codeine after oral surgery: a randomized, double-blind single-dose study.
In a randomized double-blind study, 120 patients with moderate to strong pain after surgical removal of wisdom teeth were given the following in single oral doses: 100-mg enteric-coated diclofenac tablets; 1 g acetaminophen (INN, paracetamol); 1 g acetaminophen plus 60 mg codeine; 100-mg enteric-coated diclofenac tablets plus 1 g acetaminophen; or 100-mg enteric-coated diclofenac tablets plus 1 g acetaminophen plus 60 mg codeine. Patients recorded pain intensity and pain relief for 8 hours. Upside assay sensitivity was confirmed because acetaminophen plus codeine was superior to acetaminophen. Diclofenac plus acetaminophen with and without codeine had superior analgesic effect compared with diclofenac, acetaminophen, or acetaminophen plus codeine. Addition of 60 mg codeine increased the degree of side effects. These results support the clinical practice of combining diclofenac with acetaminophen for acute pain. Of clinical importance are superior and prolonged analgesia and fewer side effects after enteric-coated diclofenac tablets plus acetaminophen compared with acetaminophen plus codeine.


DNA structure and dynamics: an atomic force microscopy study.
This review primarily outlines the most recent atomic force microscopy (AFM) studies of DNA structure and dynamics. Sample preparation techniques allowing reliable and reproducible imaging of various DNA topologies are reviewed. Such important issues as imaging of supercoiled DNA conformations at different ionic conditions and detection of local alternative structures that are stabilized by negative DNA supercoiling are discussed in length in the article. The possibility of imaging DNA structural dynamics at different levels is another major focus of the article. Using time-lapse AFM imaging mode of nondried samples, such extensive DNA dynamic processes as transition of one local structure into another (H-DNA to B-form transition), the conformational transitions of DNA Holliday junctions and their branch migration were observed. Potential future applications of this single-molecule dynamics mode of AFM to analyses of various biochemical processes involving DNA are discussed.


Postnatal development of neurotransmitter systems and their relevance to extinction of conditioned fear.
Remembering and forgetting are fundamental features of an organism. Extinction is a type of forgetting where there is a decrease in the significance and/or the meaning of an associative memory when elements of that memory no longer predict one another. The neural mechanisms underlying extinction of fear memories have been extensively studied in the laboratory because extinction processes are clinically relevant to exposure therapies that treat anxiety disorders. However, only in the last decade have we begun to unveil the similarities and differences in plasticity underlying extinction across development. So far it is clear that extinction is a developmentally dissociated process in behavior and in pharmacology, however there are many large gaps in the literature in understanding how the developmental trajectory of different neurotransmitters contribute to changes in the nature of extinction across development. We attempt to address these gaps in the present review. Major neurotransmitter systems including the glutamatergic and GABAergic systems, the monoamines, the endogenous opioid and cannabinoid systems, acetylcholines, and neuropeptides such as oxytocin have all been identified to play some role in extinction of fear memories and have been covered in this review. We hope to facilitate more research into mechanisms of extinction at different stages of life, especially noting that mental disorders are increasingly classified as neurodevelopmental disorders.


Intraperitoneal VEGF inhibition using bevacizumab: a potential approach for the symptomatic treatment of malignant ascites?
Despite overall improvements in oncological care in the palliative setting, symptomatic malignant ascites remains a severe clinical problem. This form of effusion is known to be widely resistant to established modes of systemic therapy. Accordingly, frequent paracentesis often represents the only effective way for symptom relief in patients with advanced cancer. This invasive mode of therapy, however, is often very burdensome for the patient who is already severely distressed by the underlying malignancy. Recently, the trifunctional monoclonal antibody catumaxomab given i.p. has shown symptom relief in patients with ovarian cancer and malignant ascites. On another front, the release of vascular endothelial growth factor (VEGF) by tumor cells has been identified as a main factor promoting the i.p. secretion of fluid. Accordingly, recent evidence suggests that targeting VEGF may have the potential to suspend the ascites production resulting from peritoneal metastasis. Here, we review preclinical and clinical data supporting this hypothesis. We show current evidence suggesting that the i.p. application of the anti-VEGF antibody bevacizumab, which is already in use as an i.v. therapeutic drug for a variety of tumors, might represent an effective way to prevent local fluid accumulation. Because such an effect would result in significant relief for patients, future clinical studies should stringently assess the effectiveness of this targeted therapy for the treatment of malignant i.p. effusions.


Origins of cellular geometry.
Cells are highly complex and orderly machines, with defined shapes and a startling variety of internal organizations. Complex geometry is a feature of both free-living unicellular organisms and cells inside multicellular animals. Where does the geometry of a cell come from? Many of the same questions that arise in developmental biology can also be asked of cells, but in most cases we do not know the answers. How much of cellular organization is dictated by global cell polarity cues as opposed to local interactions between cellular components? Does cellular structure persist across cell generations? What is the relationship between cell geometry and tissue organization? What ensures that intracellular structures are scaled to the overall size of the cell? Cell biology is only now beginning to come to grips with these questions.


Constant stress arches and their design space.
It is generally accepted that an optimal arch has a funicular (moment-less) form and least weight. However, the feature of least weight restricts the design options and raises the question of durability of such structures. This study, building on the analytical form-finding approach presented in Lewis (2016. Proc. R. Soc. A 472, 20160019. (doi:10.1098/rspa.2016.0019)), proposes constant axial stress as a design criterion for smooth, two-pin arches that are moment-less under permanent (statistically prevalent) load. This approach ensures that no part of the structure becomes over-stressed under variable load (wind, snow and/or moving objects), relative to its other parts-a phenomenon observed in natural structures, such as trees, bones, shells. The theory considers a general case of an asymmetric arch, deriving the equation of its centre-line profile, horizontal reactions and varying cross-section area. The analysis of symmetric arches follows, and includes a solution for structures of least weight by supplying an equation for a volume-minimizing, span/rise ratio. The paper proposes a new concept, that of a design space controlled by two non-dimensional input parameters; their theoretical and practical limits define the existence of constant axial stress arches. It is shown that, for stand-alone arches, the design space reduces to a constraint relationship between constant stress and span/rise ratio.


Heterobimetallic Complexes Featuring Fe(CO)5 as a Ligand on Gold.
Iron(0) pentacarbonyl complexes of gold(I), [Mes3 PAu-Fe(CO)5 ][SbF6 ] (1) and [(IPr*)Au-Fe(CO)5 ][SbF6 ] (2) (Mes=2,4,6-trimethylphenyl; IPr*=1,3-bis(2,6-bis(diphenylmethyl)-4-methylphenyl)imidazol-2-ylidene) have been synthesized using Mes3 PAuCl and (IPr*)AuCl as the gold(I) precursor, AgSbF6 halide ion abstractor, and the Lewis base Fe(CO)5 . The Au-Fe bond lengths of these metal-only Lewis pair complexes are significantly shorter than the sum of the experimentally derived covalent radii of Au and Fe. The v̄(CO) bands of the molecules show a notable blueshift relative to those observed for free Fe(CO)5 , indicating a substantial reduction in Fe→CO backbonding upon its coordination to gold(I) with either Mes3 P or IPr* supporting ligands (L). The analysis of the electronic structure with quantum chemical method suggests that the Au-Fe bond consists mainly of [LAu]+ ←Fe(CO)5 σ-donation and weaker [LAu]+ →Fe(CO)5 π-backdonation. The donor strength of Fe(CO)5 is similar to that of CO.


[Improvement in model of mesangial proliferative glomerulonephritis of rat].
To establish a model of mesangial proliferative glomerulonephritis (MsPGN), we gave Sprague-Dawley rats staphylococcal enterotoxin B (SEB) intravenously twice in different times, bovine serum albumine (BSA) through digestive tract every other day, and Freud's adjuvant subcutaneously twice in different times, respectively. The results showed that measangial cells and matrix in glomeruli of rats began to proliferate at the end of 6th week and this change became obvious at the end of 8th week. The duration of experiment was shorter than that using only SEB, and the change of pathomorphology was stable. The experiment confirms the thesis that mucosal immunization of gastroenteric tract plays an important role in the development of MsPGN.


Temporal evolution of altered islet neurotransmitter sensitivity after VMH lesion.
It has been suggested that increased insulin secretion after ventromedial hypothalamic (VMH) obesity is mediated by decreased sympathetic and increased parasympathetic neural input. The evolution of pancreatic islet adaptation was studied from 1 to 130 days after VMH lesion in rats by assessing the sensitivity of insulin secretion from incubated isolated islets to 10 mM glucose and selected acetylcholine and norepinephrine concentrations. Insulin secretion in response to glucose increased by 1 day, reaching a twofold plateau from 7 to 130 days. Sensitivity to norepinephrine increased by 1 day, whereas sensitivity to acetylcholine decreased by 2 days, and both remained altered up to 130 days. These data suggest that elevated plasma insulin concentrations characteristic of VMH obesity were associated with increased insulin secretion in response to glucose before decreased sensitivity to acetylcholine and concurrent with increased sensitivity to norepinephrine. We conclude that these compensatory responses, which shift the islet to a new operating point secondary to altered neural input, are essential to pancreatic adaptation in VMH obesity.


Cryptic deletions are a common finding in "balanced" reciprocal and complex chromosome rearrangements: a study of 59 patients.
Using array comparative genome hybridisation (CGH) 41 de novo reciprocal translocations and 18 de novo complex chromosome rearrangements (CCRs) were screened. All cases had been interpreted as "balanced" by conventional cytogenetics. In all, 27 cases of reciprocal translocations were detected in patients with an abnormal phenotype, and after array CGH analysis, 11 were found to be unbalanced. Thus 40% (11 of 27) of patients with a "chromosomal phenotype" and an apparently balanced translocation were in fact unbalanced, and 18% (5 of 27) of the reciprocal translocations were instead complex rearrangements with >3 breakpoints. Fourteen fetuses with de novo, apparently balanced translocations, all but two with normal ultrasound findings, were also analysed and all were found to be normal using array CGH. Thirteen CCRs were detected in patients with abnormal phenotypes, two in women who had experienced repeated spontaneous abortions and three in fetuses. Sixteen patients were found to have unbalanced mutations, with up to 4 deletions. These results suggest that genome-wide array CGH may be advisable in all carriers of "balanced" CCRs. The parental origin of the deletions was investigated in 5 reciprocal translocations and 11 CCRs; all were found to be paternal. Using customized platforms in seven cases of CCRs, the deletion breakpoints were narrowed down to regions of a few hundred base pairs in length. No susceptibility motifs were associated with the imbalances. These results show that the phenotypic abnormalities of apparently balanced de novo CCRs are mainly due to cryptic deletions and that spermatogenesis is more prone to generate multiple chaotic chromosome imbalances and reciprocal translocations than oogenesis.


Roger T. Sherman Lecture. Advances in the management of blunt thoracic aortic injury: Parmley to the present.
This article traces the evolution in management of blunt aortic injury (BAI) over the past 50 years from the time of the seminal description from Parmley in 1958. There have been major advances in both diagnostics and treatment paradigms with very rapid technologic advances occurring over the past decade. For many years, conventional aortography was the principle diagnostic tool, but it has been replaced by the progression of CT. The widespread adoption of antihypertensive therapy has sharply reduced the incidence of aortic rupture before planned reconstruction. Many patients with major associated injuries have definitive treatment of BAI managed in a delayed fashion with the use of hypertensives, which appears to improve outcomes. In the past 5 years, definitive treatment has changed with the majority of injuries being treated today with endoluminal stent grafts as opposed to open thoracotomy and traditional repair techniques. Paraplegia rates have diminished from 8 to 10 per cent down to 1 to 2 per cent in association with these therapeutic advances.


Systemic induction of monoterpene biosynthesis in Origanumxmajoricum by soil bacteria.
Italian oregano (Origanumxmajoricum) was subjected to root system inoculation with three species of plant growth-promoting rhizobacteria (PGPRs) (Pseudomonas fluorescens, Bacillus subtilis, Azospirillum brasilense), and essential oil (EO) content and plant growth were measured. Composition of monoterpenes, a major EO component, was analyzed qualitative and quantitatively by gas chromatography. Total EO yield for plants inoculated with P. fluorescens or A. brasilense was 3.57 and 3.41 microg/mg fresh weight, respectively, approximately 2.5-fold higher than controls, without change of quantitative oil composition. The major EO compounds, cis- and trans-sabinene hydrate, gamma-terpinene, carvacrol, and thymol, showed increased biosynthesis. Carvacrol was the only terpene showing significant increase of R% in plants inoculated with A. brasilense. Plant growth parameters (shoot and root fresh and dry weights, numbers of leaves and nodes) were evaluated. Shoot fresh weight was significantly increased by all three PGPR species, but only P. fluorescens and A. brasilense increased root dry weight. These two species have clear commercial potential for economic cultivation of O.xmajoricum. Knowledge of the factors affecting yield and accumulation of monoterpenes is essential for improving production of these economically important plant compounds.


Differential accumulation of proteinase inhibitor I in normal and crown gall tissue of tobacco, tomato, and potato.
A proteinase inhibitor (inhibitor I) is induced in crown gall tumors of tobacco (Nicotiana tabacum) initiated through infection with the tumorinducing bacterium, Agrobacterium tumefaciens, strains B6 or CG-14. Uninfected tissues do not contain immunologically detectable quantities of inhibitor I. Inhibitor I synthesis in tobacco crown gall tumors paralleled tumor growth at the average rate of about 4.5 mug of inhibitor I per 200 mg of fresh tissue per day. Infection of variegated tobacco mutant Dp-I with A. tumefaciens strain CG-14 produced tumors with 25% more inhibitor than tumors induced with strain B6. Unlike tobacco, tumors induced by either bacterial strain on potato (Solanum tuberosum) and on tomato (Lycopersicum esculentum) did not accumulate inhibitor I. Consequently, inhibitor I accumulation is modulated by the type of plant host used in spite of familial relatedness (Solanaceae) and the strain of A. tumefaciens used for infection.Immunological and electrophoretic properties of inhibitor I from tobacco crown gall tumor, callus, etiolated, and variegated tissues were compared. Agar immunodiffusion assays showed no apparent differences among precipitin reaction lines between inhibitor I of tumor, callus, variegated, and etiolated tissues. The immunoelectrophoretic mobilities of inhibitor I of tumor, variegated, and etiolated tissues were the same, but differed from that of either normal or crown gall callus tissues. These results suggest that different isoinhibitors of inhibitor I could account for the observed differences in electrophoretic mobilities, or that modification of the inhibitor has occurred sometime during, or after, its synthesis.


Functionalized 3D scaffolds for engineering the hematopoietic niche.
Hematopoietic stem cells (HSCs) reside in a subzone of the bone marrow (BM) defined as the hematopoietic niche where, via the interplay of differentiation and self-renewal, they can give rise to immune and blood cells. Artificial hematopoietic niches were firstly developed in 2D in vitro cultures but the limited expansion potential and stemness maintenance induced the optimization of these systems to avoid the total loss of the natural tissue complexity. The next steps were adopted by engineering different materials such as hydrogels, fibrous structures with natural or synthetic polymers, ceramics, etc. to produce a 3D substrate better resembling that of BM. Cytokines, soluble factors, adhesion molecules, extracellular matrix (ECM) components, and the secretome of other niche-resident cells play a fundamental role in controlling and regulating HSC commitment. To provide biochemical cues, co-cultures, and feeder-layers, as well as natural or synthetic molecules were utilized. This review gathers key elements employed for the functionalization of a 3D scaffold that demonstrated to promote HSC growth and differentiation ranging from 1) biophysical cues, i.e., material, topography, stiffness, oxygen tension, and fluid shear stress to 2) biochemical hints favored by the presence of ECM elements, feeder cell layers, and redox scavengers. Particular focus is given to the 3D systems to recreate megakaryocyte products, to be applied for blood cell production, whereas HSC clinical application in such 3D constructs was limited so far to BM diseases testing.


ARID1A knockdown enhances carcinogenesis features and aggressiveness of Caco-2 colon cancer cells: An in vitro cellular mechanism study.
Loss of ARID1A, a tumor suppressor gene, is associated with the higher grade of colorectal cancer (CRC). However, molecular and cellular mechanisms underlying the progression and aggressiveness of CRC induced by the loss of ARID1A remain poorly understood. Herein, we evaluated cellular mechanisms underlying the effects of ARID1A knockdown on the carcinogenesis features and aggressiveness of CRC cells. A human CRC cell line (Caco-2) was transfected with small interfering RNA (siRNA) specific to ARID1A (siARID1A) or scrambled (non-specific) siRNA (siControl). Cell death, proliferation, senescence, chemoresistance and invasion were then evaluated. In addition, formation of polyploid giant cancer cells (PGCCs), self-aggregation (multicellular spheroid) and secretion of an angiogenic factor, vascular endothelial growth factor (VEGF), were examined. The results showed that ARID1A knockdown led to significant decreases in cell death and senescence. On the other hand, ARID1A knockdown enhanced cell proliferation, chemoresistance and invasion. The siARID1A-transfected cells also had greater number of PGCCs and larger spheroid size and secreted greater level of VEGF compared with the siControl-transfected cells. These data, at least in part, explain the cellular mechanisms of ARID1A deficiency in carcinogenesis and aggressiveness features of CRC.


Anticonvulsant hypersensitivity: an unfortunate case of triple exposure to phenytoin.
Anticonvulsant hypersensitivity manifests 2 to 12 weeks after patients start taking phenytoin, phenobarbital, or carbemazepine. The syndrome begins with fever followed by a rash that can progress to erythema multiforme, toxic epidermal necrolysis, and multi-organ system involvement. Other common manifestations include lymphadenopathy, facial edema, eosinophilia, and elevated transaminase levels. Anticonvulsant hypersensitivity can be fatal in 5% to 50% of patients if hepatic involvement or toxic epidermal necrolysis occurs. Most evidence regarding the etiology points to a genetically related defect in the detoxification enzyme. Early recognition is important in order to discontinue drug therapy. Continuity of care assists in prevention of re-exposure. Treatment includes supportive measures and steroids. All patients with anticonvulsant hypersensitivity should wear a medical identification bracelet.


What are the most important factors regarding acceptance to the colonoscopy?: study of related tolerance parameters.
Colonoscopy plays an indubitable role in the setting of clinical practice, however, it is an invasive exam; complex, lengthy, embarrassing, not devoid of risks and discomfort that yields fear and anxiety in the majority of patients. In a new era of rising competition between health institutions, where the quality of health care and client satisfaction are praised, studies regarding tolerance-related colonoscopy issues yield great potential to be explored. In the present study, tolerance is defined as willingness to repeat the exam. Evaluate information associated to bowel preparation, the exam itself and post-examination period that might interfere with the tolerance to the colonoscopy. Analysis of the tolerance to the colonoscopy at three stages (pre, post, and during) through a checklist: patient's questionnaire and a medical assessment form were used. In this present study, 91.2% of 373 patients exhibited positive tolerance to the colonoscopy. Aspects related to a negative level of tolerance were patient gender (12.9% of women versus 3.2% of men would not repeat the exam), age extremes (less than 20 years and greater than 80 years of age), and abdominal pain, both during the bowel preparation and after the procedure. Gender, age, patient cooperation and abdominal pain were the decisive components regarding tolerance to the colonoscopy. Notably, in two phases of the exam, the abdominal pain was the most important feature associated to a lessened tolerance.


Changes in enzymes activity, substrate utilization pattern and diversity of soil microbial communities under cadmium pollution.
Heavy metal pollution has received increasing attention in recent years mainly because of the public awareness of environmental issues. In this study we have evaluated the effect of cadmium (Cd) on enzymes activity, substrate utilization pattern and diversity of microbial communities in soil spiked with 0, 20, 40, 60, 80, and 100 mg/kg Cd, during 60 d of incubation at 25 degrees C. Enzyme activities determined at 0, 15, 30, 45, and 60 d after heavy metal application (DAA) showed marked declines for various Cd treatments, and up to 60 DAA, 100 mg/kg Cd resulted in 50.1%, 47.4%, and 39.8% decreases in soil urease, acid phosphatase and dehydrogenase activities, respectively to control. At 60 DAA, substrate utilization pattern of soil microbial communities determined by inoculating Biolog ECO plates indicated that Cd addition had markedly inhibited the functional activity of soil microbial communities and multivariate analysis of sole carbon source utilization showed significantly different utilization patterns for 80 and 100 mg/kg Cd treatments. The structural diversity of soil microbial communities assessed by PCR-DGGE method at 60 DAA, illustrated that DGGE patterns in soil simplified with increasing Cd concentration, and clustering of DGGE profiles for various Cd treatments revealed that they had more than 50% difference with that of control.


Successful catheter ablation of human ventricular tachycardia with radiofrequency current guided by an endocardial map of the area of slow conduction.
A case is presented of a 68-year-old male patient with a history of myocardial infarction and recurrent ventricular tachycardia who was successfully treated with a single 20-second transcatheter application of radiofrequency current. Prior to current application a complete endocardial map had been obtained of an area of slow conduction that extended caudo-cranially for approximately 2 cm along the lower left ventricular septum. Stimulation techniques yielded evidence that this area was critically related to tachycardia initiation and maintenance. Its central part was subsequently chosen as the site for current delivery.


Synthesis, molecular docking studies of coumarinyl-pyrazolinyl substituted thiazoles as non-competitive inhibitors of mushroom tyrosinase.
A series of coumarinyl-pyrazolinyl substituted thiazoles derivatives were synthesized and their inhibitory effects on the DPPH and mushroom tyrosinase were evaluated. The results showed that all of the synthesized compounds exhibited significant mushroom tyrosinase inhibitory activities. In particular, 3-(5-(4-(benzyloxy)-3-methoxyphenyl)-1-(4-(4-bromophenyl)thiazol-2-yl)-4,5-dihydro-1H-pyrazol-3-yl)-2H-chromen-2-one (7j) exhibited the most potent tyrosinase inhibitory activity with IC50 value 0.00458±0.00022μM compared with the IC50 value of kojic acid is 16.84±0.052μM. The inhibition mechanism analyzed by Lineweaver-Burk plots revealed that the type of inhibition of compound 7j on tyrosinase was noncompetitive. The docking study against tyrosinase enzyme was also performed to determine the binding affinity of the compounds. The compound 7a showed the highest binding affinity (-10.20kcal/mol) with active binding site of tyrosinase. The initial structure activity relationships (SARs) analysis suggested that further development of such compounds might be of interest. The statistics of our results endorses that compound 7j may serve asa structural template for the design and development of novel tyrosinase inhibitors.


[A quality of life study in women with systemic lupus erythematosus and its relation to disease activity].
To determined in a prospective study the quality of life (QoL) in the systemic lupus erythematosus (SLE) females. We also studied the relationship between QoL and the activity of lupus disease. We studied 67 consecutive SLE females. To study the QoL we administered the Medical Outcomes Study Short form Scale SF-36 (MOS-SF36). This questionnaire is composted for 36 question and comprises eighth subscales of QoL. We also measured the activity with the Mexico-SLE Disease Activity Index (MEX-SLEDAI). The mean age of the 67 SLE patients at disease onset was 38.3 +/- 14 years, and mean duration of disease was 66 +/- 42 months. The values of QoL answers were lower. No relationship was found between the age of patients and QoL. The subscales with poor punctuation were the general heath and the role physical. Multiple variate analyses showed that activity was associated with vitality (r = 0.36; p = 0.003). The MOS-SF36 questionnaire indicate that SLE females patients had lower results about her quality of life.


Metrological Characterization and Comparison of D415, D455, L515 RealSense Devices in the Close Range.
RGB-D cameras are employed in several research fields and application scenarios. Choosing the most appropriate sensor has been made more difficult by the increasing offer of available products. Due to the novelty of RGB-D technologies, there was a lack of tools to measure and compare performances of this type of sensor from a metrological perspective. The recent ISO 10360-13:2021 represents the most advanced international standard regulating metrological characterization of coordinate measuring systems. Part 13, specifically, considers 3D optical sensors. This paper applies the methodology of ISO 10360-13 for the characterization and comparison of three RGB-D cameras produced by Intel® RealSense™ (D415, D455, L515) in the close range (100-1500 mm). ISO 10360-13 procedures, which focus on metrological performances, are integrated with additional tests to evaluate systematic errors (acquisition of flat objects, 3D reconstruction of objects). The present paper proposes an off-the-shelf comparison which considers the performance of the sensors throughout their acquisition volume. Results have exposed the strengths and weaknesses of each device. The D415 device showed better reconstruction quality on tests strictly related to the short range. The L515 device performed better on systematic depth errors; finally, the D455 device achieved better results on tests related to the standard.


Cognitive bias modification procedures in the management of mental disorders.
To review recent research on the therapeutic impact of cognitive bias modification (CBM) procedures, designed to train direct change in the patterns of attentional and interpretive bias known to characterize particular forms of psychopathology. CBM designed to change attentional selectivity has proven capable of modifying attentional biases associated with emotional dysfunction, pain disorders, eating disorders and addictions. CBM designed to change interpretive selectivity has proven capable of modifying the tendency to resolve ambiguity in a negative manner that is characteristic of emotional dysfunction. Recent research confirms that both forms of CBM can alter the severity of symptoms associated with psychopathology. Extended delivery of such CBM approaches now has been shown to yield therapeutic benefits for a range of anxiety disorders, and in the case of CBM-A has augmented the efficacy of treatment for alcohol dependence. CBM approaches have passed the proof-of-concept stage, and recent small-scale trials attest to their likely clinical value. There is a pressing need for large-scale randomized controlled trials, to compare the efficacy of CBM with that of alternative approaches, and to identify how CBM can most effectively be integrated into multimodal treatment programs.


Selective expression of immune-associated surface antigens by keratinocytes in irritant contact dermatitis.
The expression of three immunoregulatory surface antigens by epidermal keratinocytes was studied in irritant contact dermatitis (ICD), in order to assess whether keratinocytes have a modulatory role in the pathogenesis of this disorder. Biopsies were taken from 48-h patch test reactions to six structurally unrelated irritants, and frozen sections immunolabeled with monoclonal antibodies to the major histocompatibility complex class II antigen, HLA-DR, intercellular adhesion molecule-1 (ICAM-1), and the 88-Kd glycoprotein CD36 (OKM5), as well as to the CD3 (T cells) and CD11a (lymphocyte function associated antigen-1, LFA-1) antigens. We found that there was very limited expression of HLA-DR by keratinocytes, with no correlation between the extent of HLA-DR positivity and the degree of T cell infiltration into the epidermis and dermis, suggesting that interferon gamma may not be a significant mediator of ICD at 48 h. In contrast, keratinocytes showed extensive upregulation of ICAM-1, with an excellent spatial association between ICAM-1 expression and LFA-1 positive leucocytes in the epidermis. This indicates that keratinocyte ICAM-1 induction is not restricted to diseases in which antigen presentation is pivotal, but that it has a generalized role in cutaneous inflammatory reactions, promoting the infiltration of leucocytes into the epidermis. Immunolabeling with OKM5 revealed that CD36 is present to a variable degree on keratinocytes in normal skin. Differential changes in the pattern of keratinocyte expression occurred between irritants, in a manner that suggested that the CD36 antigen does not act as an adhesion molecule in ICD, but rather that its expression is related to the proliferative state of the epidermis. The results of this study demonstrate that immune-associated antigens are selectively expressed on the surface of keratinocytes in 48-h ICD biopsies, implying that these cells play an important regulatory role in the development of the inflammatory response to irritant chemicals.


Angiotensin converting enzyme in patients with sleep apnoea syndrome: plasma activity and gene polymorphisms.
The prevalence of several cardiovascular diseases is increased with obstructive sleep apnoea syndrome (OSAS), due to, as yet, unclear reasons. Angiotensin converting enzyme (ACE) abnormalities have been implicated in the pathogenesis of various cardiovascular diseases. In this study, plasma ACE activity and the distribution of an insertion (I)/deletion (D) polymorphism of the ACE gene were determined in OSAS patients and in healthy controls. A total of 63 patients with OSAS (mean+/-SEM 54.5+/-2.5 apnoea/hypopnoeas.h(-1)) and 32 healthy subjects were studied. To avoid potential confounding factors, patients treated with ACE inhibitors or continuous positive airway pressure were excluded, as well as controls in whom a blood sample was not obtained early in the morning. ACE activity was determined spectrophotometrically in 46 OSAS patients and 25 controls. The I/D ACE polymorphism was determined by polymerase chain reaction in 44 patients and 32 controls. ACE activity was higher in OSAS patients (53.9+/-2.5 IU.L(-1)) than in healthy controls (42.4+/-3.1 IU.L(-1), p<0.01). This was independent of the presence of arterial hypertension. The frequency distribution of the DD, II and ID genotypes in OSAS patients (30%, 16%, 54%, respectively) was not significantly different from that seen in healthy subjects (31%, 28%, 41%, respectively, p=0.356). These results indicate that ACE plasma activity is increased in untreated OSAS patients. This increased activity may contribute to the pathogenesis of the cardiovascular disease in these patients.


Qualitative assessment of interorganisational partnership at a perinatal and family substance abuse centre: stakeholders' perceptions of quality and development of their collaboration.
Partnerships are required in health and social care services to meet the increasingly complex needs of vulnerable populations. It is essential to assess these partnerships to ensure partners are supported as they strive to improve their practices. This qualitative study assessed the quality and development of the partnership of an integrated service centre for pregnant women and substance-abusing parents and their young children aged 5 and under. The data were gathered over a period of three years, by means of group and individual interviews. Twenty respondents (practitioners and managers) shared their perceptions of the interagency collaboration at the beginning, the midpoint and the end of the project funding period. Their responses were examined by means of thematic analysis. Conditions facilitating or hindering implementation of the partnership included (a) partners' participation and engagement; (b) nature of the project and its functioning (aspects of governance); (c) partners' joint work with families; and (d) social and political issues. The study highlights critical elements to consider for the development and success of a partnership project. Participants reported a number of barriers to effective collaboration; the main ones, the importance of thorough planning of project implementation, as well as the challenges relating to communication and shared leadership, are discussed.


Youth Bullying and Suicide: Risk and Protective Factor Profiles for Bullies, Victims, Bully-Victims and the Uninvolved.
Bullying is closely associated with suicide. This study validates mixed evidence on whether young bullies, victims, bully-victims, and those uninvolved in bullying differ in suicidality, risk, protective factor profiles, and predictors of suicide. A total of 2004 Hong Kong adolescents and young adults completed the Hong Kong Online Survey on Youth Mental Health and Internet Usage in 2018. Bullies, victims, and bully victims, as opposed to the uninvolved, were found to possess higher tendencies of suicidal thoughts and behaviors. They had more distinct rather than overlapping risk and protective factor profiles yet shared psychological distress and diagnosis of a psychiatric disorder as common predictors of suicide. The results indicate that suicide screening assessments and training to detect common suicide predictors can benefit youngsters regardless of their bullying involvement. From the discussion, group-specific interventions include restorative justice approaches to promote reintegration and help-seeking among bullies, peer, and professional support programs geared towards lowering victim isolation and equipping gatekeepers such as teachers with skills to connect with both bullies and victims.


[Experiences in surgical management of acute arterial occlusions of the lower limb in the course of 20 years].
In Hungary surgeons perform every year more then 2000 operations for treatment of acute arterial occlusion. Because of the advanced age and poor general condition of these patients, the postoperative mortality and complication rate is considerable. Authors analyzed changes in the etiology and therapy of acute arterial occlusions of lower limb in the last 20 years in a retrospective study. 563 patients were operated on with acute arterial occlusion of lower extremities from 1983 to 2002 by the authors. Patients with vascular surgery in their history were excluded from this study. Student's two-samples "t"-test, chi2- and Fisher's exact test were used in Statistica 6.0 for statistics. Period of 1983-1992 compared to period of 1993-2002 they found increased rate of occlusions caused by thrombosis (35 vs. 46%, p < 0.01) and increased number of acute vascular reconstructions performed with indication of acute thrombosis (17.6 vs. 47.0%, p < 0.001). Mortality was higher in patients operated with embolism than in patients with thrombosis (17.7 vs. 11.6%, p < 0.01), but the ratio of postoperative amputation following embolectomy was lower than following thrombectomy (5.0 vs. 16.0%, p < 0.01). Thrombectomy itself could solve the occlusion caused by thrombosis only in 50% of cases. Results of reoperations following unsuccessful thrombectomies are very poor. Amputation was necessary in 6.8% (in 5 cases of 74 patients) after primary reconstructions, but in 28.6% (in 14 cases of 49 patients) after reoperations. There was no significant difference in postoperative mortality among primary reconstructed, reoperated and conservatively treated groups. By author's experience, in cases of acute occlusion caused by thrombosis as a complication of chronic obliterative arterial disease, basic cause of occlusion should be searched for and--if conditions are suitable--procedure should be extend to vascular reconstruction.


Raf-1 kinase regulates smooth muscle contraction in the rat mesenteric arteries.
We investigated the potential role of Raf-1 kinase in mesenteric arterial contraction. Inhibitors of Raf-1 kinase, GW5074, L779450 and ZM 336372 reversed phenylephrine (PE)-induced mesenteric vascular contraction. Studies in vivo in rats showed that GW5074 inhibited PE-induced increase in mean arterial pressure in adult female Sprague-Dawley rats. Isometric tension studies in mesenteric arteries of rats showed that GW5074 did not change the KCl-evoked contraction but significantly inhibited the contractions to PE, 5-HT, U46619, endothelin 1, angiotensin II and phorbol 12, 13-dibutyrate (PDBu). In mesenteric vascular smooth muscle cells (VSMCs), PE stimulated increase in Raf-1 phosphorylation which was inhibited by GW5074. Measurement of [Ca(2+)](i) with Fura-2 showed that GW5074-mediated inhibition of PE-induced contraction was not associated with decreases in [Ca(2+)](i). VSMCs treated with PE exhibited higher levels of the contractile proteins, p-MYPT1 and p-MLC(20), which was inhibited by GW5074. Similarly, PDBu induced increases in phosphorylation of Raf-1, MLC(20) and MYPT1 and this was inhibited by GW5074. However, GW5074 did not have any significant effect on PE/PDBu-induced MEK/ERK activation. The results indicate that Raf-1 kinase plays an important role in the regulation of vascular contractility through regulation of calcium sensitization.


Health Care Use Among Latinx Children After 2017 Executive Actions on Immigration.
US immigration policy changes may affect health care use among Latinx children. We hypothesized that January 2017 restrictive immigration executive actions would lead to decreased health care use among Latinx children. We used controlled interrupted time series to estimate the effect of executive actions on outpatient cancellation or no-show rates from October 2016 to March 2017 ("immigration action period") among Latinx children in 4 health care systems in North Carolina. We included control groups of (1) non-Latinx children and (2) Latinx children from the same period in the previous year ("control period") to account for natural trends such as seasonality. In the immigration action period, 114 627 children contributed 314 092 appointments. In the control period, 107 657 children contributed 295 993 appointments. Relative to the control period, there was an immediate 5.7% (95% confidence interval [CI]: 0.40%-10.9%) decrease in cancellation rates among all Latinx children, but no sustained change in trend of cancellations and no change in no-show rates after executive immigration actions. Among uninsured Latinx children, there was an immediate 12.7% (95% CI: 2.3%-23.1%) decrease in cancellations; however, cancellations then increased by 2.4% (95% CI: 0.89%-3.9%) per week after immigration actions, an absolute increase of 15.5 cancellations per 100 appointments made. There was a sustained increase in cancellations among uninsured Latinx children after immigration actions, suggesting decreased health care use among uninsured Latinx children. Continued monitoring of effects of immigration policy on child health is needed, along with measures to ensure that all children receive necessary health care.


Human glioblastoma cells release interleukin 6 in vivo and in vitro.
This study demonstrates interleukin 6 (IL-6) production and release by human glioblastomas. Twenty glioblastoma cell lines were tested for IL-6 bioactivity using an IL-6-dependent cell line (7TD1). All of the lines tested with one exception (LN-229) constitutively released IL-6. A significant induction of IL-6 production and secretion was observed when LN-229 cells were treated with interleukin 1 beta (IL-1 beta) or tumor necrosis factor alpha. Various amounts of IL-6 mRNA were found in five of six cell lines tested. IL-6 mRNA was detected in line LN-229 only when the cells were treated with IL-1 beta or tumor necrosis factor alpha, confirming the bioassay data. Glioblastoma cells also produce IL-6 in vivo. (a) IL-6 activity was detected in 11 of 13 cerebrospinal fluids and five of five tumor cyst fluids. (b) IL-6 mRNA was found in four of four tumors. (c) Immunohistochemical analysis showed IL-6 within the tumor cells in 15 of 20 glioblastoma sections. In conclusion, biologically active IL-6 is released by almost all glioblastomas both in vitro and in vivo. The elevated levels of serum acute phase proteins and immune complexes found in glioblastoma patients may be the result of this secretion.


Genetic variation and hitchhiking between structurally polymorphic Alu insertions and HLA-A, -B, and -C alleles and other retroelements within the MHC class I region.
We investigated structurally polymorphic Alu insertions (POALINs) at five loci in the major histocompatibility complex (MHC) class I genomic region to determine their allele and haplotype frequencies and associations with the human leukocyte antigen (HLA)-A, -B, and -C genes in three populations, the Australian Caucasians, Japanese, and African Americans. The POALINs varied in allelic frequency between 0% and 42.3% with significant differences between populations at three of the five loci. The linkage disequilibrium (LD) between Alu insertions and the HLA-A, -B, or -C alleles and previously published polymorphic retroelements (four SVA and human endogenous retrovirus type 9 (HERVK9) loci) within the class I region of the MHC were calculated in pairwise analyses of haplotypes to show strong allelic associations and possible crossing-over events between some loci. Each POALIN was in significant LD with a variety of HLA-A, -B, or -C two-digit alleles probably as a result of hitchhiking. The POALINs helped to further stratify the HLA-A:B:C haplotypes into different POALIN:HLA-A:B:C haplotype frequencies. Of the multilocus haplotype analyses, the seven- and eight-locus haplotypes showed the largest number of differences between the populations, and fewer matched haplotypes between populations that ranged, for example, from 49% for HLA-B:HLA-A haplotypes to 7% for AluMICB:HLA-B:HLA-C:AluTF:AluHJ:HLA-A:AluHG:AluTF haplotypes in the Japanese. This comparative study of multilocus POALINs in the HLA class I region of three ethnic populations shows that POALINs alone or together with the HLA class I alleles and other retroelements are informative ancestral markers for assessing the interrelationship of HLA class I haplotype lineages, LD, and genetic diversity within the same and/or different populations.


Temperature-dependent changes in the microbial storage flora of birch and spruce sawdust.
Sawdust can be used to make pellets (biofuel) and particle boards and as a potential lignocellulose feedstock in bioethanol production. Microbial activity can affect sawdust quality; hence, we monitored the microbial population in birch- and spruce sawdust after 3 months' storage at various temperatures. Species composition was similar on both materials but was strongly influenced by temperature. Bacteria were present on all materials at all conditions: on birch, 2.8 × 10(8) , 1.1 × 10(8) , and 8.8 × 10(6) , and on spruce, 4.1 × 10(8) , 5.6 × 10(7) , and 1.5 × 10(8) CFU/g DM, at 2, 20, and 37 °C, respectively. Dominant bacteria at 2, 20, and 37 °C were Pseudomonas spp. (some Enterobacteriaceae spp. present), Luteibacter rhizovicinus, and Fulvimonas sp., respectively. Pseudomonas spp. were absent at ≥20 °C. Among microfungi, yeasts dominated at 2 °C but were absent at 37 °C, whereas molds dominated at 20 and 37 °C. Common yeasts included Cystofilobasidium capitatum, Cystofilobasidium infirmominiatum, Candida saitoana, Candida oregonensis, and Candida railenensis. Ophiostoma quercus was a common mold at 2 and 20 °C, whereas the human pathogens Aspergillus fumigatus and Paecilomyces variotii dominated at 37 °C. Attempts to influence the microflora by addition of the biocontrol yeasts, Wickerhamomyces anomalus and Scheffersomyces stipitis, were unsuccessful, as their growth in sawdust was poor to absent.


Haplotype-resolved de novo assembly using phased assembly graphs with hifiasm.
Haplotype-resolved de novo assembly is the ultimate solution to the study of sequence variations in a genome. However, existing algorithms either collapse heterozygous alleles into one consensus copy or fail to cleanly separate the haplotypes to produce high-quality phased assemblies. Here we describe hifiasm, a de novo assembler that takes advantage of long high-fidelity sequence reads to faithfully represent the haplotype information in a phased assembly graph. Unlike other graph-based assemblers that only aim to maintain the contiguity of one haplotype, hifiasm strives to preserve the contiguity of all haplotypes. This feature enables the development of a graph trio binning algorithm that greatly advances over standard trio binning. On three human and five nonhuman datasets, including California redwood with a ~30-Gb hexaploid genome, we show that hifiasm frequently delivers better assemblies than existing tools and consistently outperforms others on haplotype-resolved assembly.


Sulfur metabolism in Beggiatoa alba.
The metabolism of sulfide, sulfur, and acetate by Beggiatoa alba was investigated under oxic and anoxic conditions. B. alba oxidized acetate to carbon dioxide with the stoichiometric reduction of oxygen to water. In vivo acetate oxidation was suppressed by sulfide and by several classic respiratory inhibitors, including dibromothymoquinone, an inhibitor specific for ubiquinones. B. alba also carried out an oxygen-dependent conversion of sulfide to sulfur, a reaction that was inhibited by several electron transport inhibitors but not by dibromothymoquinone, indicating that the electrons released from sulfide oxidation were shuttled to oxygen without the involvement of ubiquinones. Intracellular sulfur stored by B. alba was not oxidized to sulfate or converted to an external soluble form under aerobic conditions. On the other hand, sulfur stored by filaments of Thiothrix nivea was oxidized to extracellular soluble oxidation products, including sulfate. Sulfur stored by filaments of B. alba, however, was reduced to sulfide under short-term anoxic conditions. This anaerobic reduction of sulfur was linked to the endogenous oxidation of stored carbon and to hydrogen oxidation.


Pomegranate-like N,P-Doped Mo2C@C Nanospheres as Highly Active Electrocatalysts for Alkaline Hydrogen Evolution.
Well-defined pomegranate-like N,P-doped Mo2C@C nanospheres were prepared by simply using phosphomolybdic acid (PMo12) to initiate the polymerization of polypyrrole (PPy) and as a single source for Mo and P to produce N,P-doped Mo2C nanocrystals. The existence of PMo12 at the molecular scale in the polymer network allows the formation of pomegranate-like Mo2C@C nanospheres with a porous carbon shell as peel and Mo2C nanocrystals well-dispersed in the N-doped carbon matrix as seeds. This nanostructure provides several favorable features for hydrogen evolution application: (1) the conductive carbon shell and matrix effectively prevent the aggregation of Mo2C nanocrystals and facilitate electron transportation; (2) the uniform N,P-doping in the carbon shell/matrix and plenty of Mo2C nanocrystals provide abundant catalytically highly active sites; and (3) nanoporous structure allows the effective exposure of active sites and mass transfer. Moreover, the uniform distribution of P and Mo from the single source of PMo12 and N from PPy in the polymeric PPy-PMo12 precursor guarantees the uniform N- and P-co-doping in both the graphitic carbon matrix and Mo2C nanocrystals, which contributes to the enhancement of electrocatalytic performance. As a result, the pomegranate-like Mo2C@C nanospheres exhibit extraordinary electrocatalytic activity for the hydrogen evolution reaction (HER) in terms of an extremely low overpotential of 47 mV at 10 mA cm(-2) in 1 M KOH, which is one of the best Mo-based HER catalysts. The strategy for preparing such nanostructures may open up opportunities for exploring low-cost high-performance electrocatalysts for various applications.


Modulating human connective tissue progenitor cell behavior on cellulose acetate scaffolds by surface microtextures.
Soft lithography techniques are used to fabricate cellulose acetate (CA) scaffolds with surface microtextures to observe growth characteristics of the progeny of human marrow-derived connective tissue progenitor cells (CTPs). Human CTPs were collected and cultured on CA scaffolds comprised postmicrotextures and smooth surfaces for up to 30 days. Cells on the smooth surfaces migrated without any preferred orientation for up to 30 days. On microtextures, cells tended to direct their processes toward posts and other cells on day 9. By day 30, cells on microtextures covered the surface with extracellular matrix. DNA quantification revealed approximately threefold more cells on microtextures than on the smooth surfaces. The alkaline phosphatase (AP) mRNA expression was slightly higher on smooth surfaces on day 9. However, by day 30, AP mRNA showed higher expression on microtextures. The mRNA expression of collagen type I was increased on microtextures by day 30, whereas smooth surfaces demonstrated similar expression. The osteocalcin mRNA expression was increased on postmicrotextures relative to smooth surfaces by day 30.


[The impact of nasal obstruction on OSAHS].
To evaluate the impact of nasal obstruction on OSAHS. One hundred and twenty cases of OSAHS with or without nasal obstruction were analyzed by Hypno PTT(PTT)and Mallampati score (MS); Acoustic rhinometry was measured in all 120 cases. A significant correlation was found between the MS and the AHI measured during the sleep (r = 0.266, P < 0.01). The relative risk of OSAHS with a MS of III or IV in the whole group was 1.96, and 2.46 in cases with nasal obstruction. A high MS represents a predisposing factor for OSAHS, especially in which associated with nasal obstruction.


Cognitive-behavioural group intervention for climacteric syndrome.
During peri- and postmenopause there is a high prevalence of psychological symptoms such as emotional instability, depressive moods, anxiety, sleep disorders, and sexual dysfunction. Aetiologically relevant factors for discomfort are decline of sex hormones and psychosocial factors such as lifestyle, attitude towards menopause, pre-menopausal mental health and sociocultural factors. In contrast to the relevance of psychosocial factors, there are few studies on psychological interventions. The present study evaluates an open trial of cognitive-behavioural group intervention consisting of psychoeducation, group discussion and coping skills training for women suffering from climacteric symptoms. Thirty women were enrolled in this first trial. Standardised (MRS, HADS-D, Partnership Questionnaire, McCoy Female Sexuality Questionnaire) and especially developed ('Attitudes Towards the Menopause') instruments were administered 3 times, twice before (T1 and T2) and once after the group intervention (T3). General linear model repeated measures were used to analyse changes in questionnaire measures. Taking the average of the two pre-intervention scores, significant improvements were observed in anxiety (p < 0.01), depression (p < 0.02), partnership relations (p < 0.02), overall score of sexuality (p < 0.02), hot flashes (p < 0.01) and cardiac complaints (p < 0.01) from pre- to post-intervention. No changes were found for sexual satisfaction and stressfulness of menopausal symptoms. This pilot study points at a possible effectiveness of cognitive-behavioural interventions for the treatment of climacteric syndrome. Further studies will have to use randomised trials, comparing different treatments (HRT, phyto-oestrogens, relaxation training, discussion groups) for their effectiveness.


Exploring prenatal testing preferences among US pregnant individuals: A discrete choice experiment.
Although there are numerous benefits to diagnostic prenatal testing, such as fetal exome sequencing, there are also consequences, including the possibility of receiving variants of uncertain significance or identifying secondary findings. In this study, we utilized a survey-based discrete choice experiment to elicit the preferences of pregnant people in Northern California for hypothetical prenatal genomic tests. Pregnant individuals were invited to complete the survey through advertisements on social media. Five test attributes were studied: likelihood of getting a result, time taken to receive results, who explains results, reporting of uncertain results, and reporting of secondary findings. The survey also gathered information about the participants' demographics, current and past pregnancies, and tolerance of uncertainty using the IUS-12 scale. Participants were eligible if they were female, currently 24 or more weeks pregnant, and able to read/write enough English or Spanish to complete an online survey. Overall, participants (n = 56) preferred the option of having a prenatal test over not having a prenatal test (p < 0.01) and had substantially higher preferences for tests with the highest likelihood of getting a result (p < 0.01). There were also positive preferences for tests that reported secondary findings (p = 0.01) and those where results were returned by a genetic specialist (vs. their prenatal provider) (p = 0.04). These findings can be used to guide conversations between pregnant individuals and genetics specialists, such as genetic counselors, as they weigh the pros and cons of diagnostic prenatal testing options.


The effects of familism and cultural justification on the mental and physical health of family caregivers.
We aimed to examine the effects of 2 factors of familism (Familial Obligations and Expected Support from the Family) and Cultural Justification on caregivers' mental and physical health as mediated by coping style. We used a probability sample of 95 African American and 65 White family caregivers for people with dementia to test hypotheses based on the updated sociocultural stress and coping model using path analysis. Main outcome measures included depressive symptomatology, various psychological symptoms, and subjective physical health. Both Familial Obligations and Cultural Justification had an indirect effect on poor mental health and subjective physical health via avoidant coping. Expected Support from the Family had no effect on caregivers' health outcomes. These findings suggest that feelings of obligation may be accounting for a significant proportion of the negative effects of familism on caregivers' mental and subjective physical health. Expectations of familial social support may be relatively inconsequential in this process.


Identification and Optimization of Novel Small-Molecule Cas9 Inhibitors by Cell-Based High-Throughput Screening.
CRISPR/Cas9 has revolutionized several areas of life science; however, methods to control the Cas9 activity are needed for both scientific and therapeutic applications. Anti-CRISPR proteins are known to inhibit the CRISPR/Cas adaptive immunity; however, in vivo delivery of such proteins is problematic. Instead, small-molecule Cas9 inhibitors could serve as useful tools due to their permeable, proteolytically stable, and non-immunogenic nature. Here, we identified a small-molecule ligand with anti-CRISPR/Cas9 activity through a high-throughput screening utilizing an Escherichia coli selection system. Extensive structure-activity relationship studies, which involved a deconstruction-reconstruction strategy, resulted in a range of analogues with significant improvements in the inhibitory activity. Based on NMR and electrophoretic mobility shift assays, we propose that the inhibitory action of these compounds likely results from direct binding to apo-Cas9, preventing Cas9:gRNA complex formation. These molecules may find use as Cas9 modulators in various applications.


Correlation of injury severity and tissue Evans blue content, lipid peroxidation and clinical evaluation in acute spinal cord injury in rats.
To demonstrate the changes in microvascular permeability occurring in association with graded acute spinal cord injury and to determine whether tissue Evans blue content is a useful indicator of the severity of spinal cord injury. The study also aimed to test the ability of the Evans blue method to demonstrate secondary injury after spinal cord contusion. In step one of the study, spinal cord lipid peroxidation levels and spinal cord Evans blue content were evaluated at 2 h post-injury in five groups of rats: a control group, a laminectomy-only group and three trauma groups (10, 50, and 100 gcm). In step two, these rats were used for Evans blue assessment following clinical examination at 24 h post-injury. The laminectomy-only group showed no difference from the control group with regard to spinal cord lipid peroxidation levels, tissue Evans blue content, and clinical findings. Increase in spinal cord tissue Evans blue content and lipid peroxidation was correlated with increasing intensity of trauma. There was a negative correlation between trauma intensity and clinical findings, and there was an increase in spinal cord tissue Evans blue content at 24 h compared with that at 2 h. Determination of spinal cord tissue Evans blue content is a reliable, rapid, simple and inexpensive method that can be used in experimental spinal cord injury to assess the severity of injury and to evaluate neuroprotection studies. The present study is the first to show that the Evans blue technique is a useful method to demonstrate secondary injury of spinal cord tissue and vasculature.


Photoexcited triplet state properties of brominated and nonbrominated Ga(III)-corroles as studied by time-resolved electron paramagnetic resonance.
The effect of the corrole macrocycle bromination on its photoexcited triplet state parameters was examined in a comparison study of brominated and nonbrominated Ga(III) 5,10,15-tris(pentafluorophenyl)corroles, employing X-band (9.5 GHz) time-resolved electron paramagnetic resonance (TREPR) spectroscopy. It is demonstrated that the spectrum of the brominated Ga-corrole is characterized by an opposite polarization pattern and a larger zero-field splitting (ZFS) parameter |D|, compared to nonbrominated Ga-corrole. With the assignment of a negative sign for the ZFS parameter D, the dominant intersystem crossing (ISC) pathways are evaluated. Spectral line shape analysis reveals that in the brominated Ga-corrole,the out-of-plane triplet sublevel is overpopulated (A(Z) > A(X), A(Y)), while in nonbrominated Ga-corrole, the in-plane triplet sublevels are preferentially populated (A(X), A(Y) ≫ A(Z)). The differences in the photophysical properties of the corroles are attributed to the heavy atom effect upon corrole skeleton bromination, which enhances the spin-orbit coupling strength in the brominated complex, thus affecting its ISC and ZFS parameters.


Comparison of examination fees and availability of routine vision care by optometrists and ophthalmologists.
A national telephone survey of eye care practitioners shows that the average fee for routine eye examinations was less among optometrists than ophthalmologists. The average wait for the earliest appointment was 5 days for optometrists and 20 days for ophthalmologists. Weekend and evening appointments were also more obtainable among optometrists. The study did not determine what tests were included in the routine examination of each practitioner. Optometrists are licensed to use diagnostic drugs in all 50 States and prescribe therapeutic drugs for the treatment of ocular diseases in 25 States. Legislation that would update State laws permitting doctors of optometry to prescribe and use pharmaceutical agents for the treatment of eye diseases has been introduced in many of the remaining States. Supporters of bills permitting therapeutic pharmaceutical optometry contend that these changes would ensure the availability of quality eye care at significant savings, since optometric fees are generally lower than ophthalmological fees. In addition, it has been argued that optometrists are equitably distributed geographically and are more likely to have weekend and evening office hours, thus enabling increased patient access to eye care. When considering cost-effectiveness and accessibility, this study may provide information to those States considering changes in the scope of optometric licensure.


SEM evidence that one ameloblast secretes one keyhole-shaped enamel rod in monkey teeth.
Primate enamel is subdivided into inner enamel, having Hunter-Schreger bands, and outer enamel with all rods parallel to each other. Outer inter-rod enamel may surround each rod, lie between rows of rods, or be absent, as in the 'keyhole pattern', which is composed entirely of rods. One theory on the formation of the 'keyhole' pattern overlays the hexagonal cross-sectional shape of four or more ameloblasts over the keyhole shape of the enamel rod. This ignores the likelihood that Tomes processes have a different shape from the cell body, and also ignores the observation that paths of enamel rods sometimes diverge. Scanning electron microscopy (SEM) revealed the keyhole shape of the forming face of monkey enamel. These forming rods were arranged in stepped rows with the head regions in each row separated by the tails of the preceding row. Consequently, each forming face of a rod was surrounded on three sides by previously formed enamel. The apical surface of the Tomes process was shaped exactly like the forming rod face, permitting direct apposition of one rod and one Tomes process. The conclusion was that, in the monkey, each rod of the keyhole enamel configuration is produced by one ameloblast.


Interkingdom Cross-Talk in Times of Stress: Salmonella Typhimurium Grown in the Presence of Catecholamines Inhibits Porcine Immune Functionality in vitro.
In stressful situations, catecholamines modulate mammalian immune function, and in addition, they can be sensed by many bacteria. Catecholamine sensing was also found in the zoonotic gut pathogen Salmonella Typhimurium, probably contributing to the stress-induced increased risk of salmonellosis. Virulence traits such as proliferation and invasiveness are promoted upon bacterial catecholamine sensing, but it is unknown whether S. Typhimurium may also inhibit mammalian immune function in stressful situations. We thus investigated whether supernatants from S. Typhimurium grown in the presence of catecholamines modulate porcine mitogen-induced lymphocyte proliferation. Lymphocyte proliferation was reduced by supernatants from catecholamine-exposed Salmonella in a dose-dependent manner. We further examined whether adrenaline oxidation to adrenochrome, which is promoted by bacteria, could be responsible for the observed effect, but this molecule either enhanced lymphocyte functionality or had no effect. We could thereby exclude adrenochrome as a potential immunomodulating agent produced by S. Typhimurium. This study is the first to demonstrate that bacteria grown in the presence of catecholamine stress hormones alter their growth environment, probably by producing immunomodulating substances, in a way that host immune response is suppressed. These findings add a new dimension to interkingdom signaling and provide novel clues to explain the increased susceptibility of a stressed host to Salmonella infection.