A paradigm for ethanol consumption in head-fixed mice during prefrontal cortical two-photon calcium imaging.
The prefrontal cortex (PFC) is a hub for cognitive behaviors and is a key target for neuroadaptations in alcohol use disorders. Recent advances in genetically encoded sensors and functional microscopy allow multimodal in-vivo PFC activity recordings at subcellular and cellular scales. While these methods could enable a deeper understanding of the relationship between alcohol and PFC function/dysfunction, they typically require animals to be head-fixed. Here, we present a method in mice for binge-like ethanol consumption during head-fixation. Male and female mice were first acclimated to ethanol by providing home cage access to 20% ethanol (v/v) for 4 or 8 days. After home cage drinking, mice consumed ethanol from a lick spout during head-fixation. We used two-photon calcium imaging during the head-fixed drinking paradigm to record from a large population of PFC neurons (>1000) to explore how acute ethanol affects their activity. Drinking exerted temporally heterogeneous effects on ACC activity at single neuron and population levels. Intoxication modulated the tonic activity of some neurons while others showed phasic responses around ethanol receipt. Population level activity did not show tonic or phasic modulation but tracked ethanol consumption over the minute-timescale. Network level interactions assessed through between-neuron pairwise correlations were largely resilient to intoxication at the population level while neurons with increased tonic activity showed higher synchrony by the end of the drinking period. By establishing a method for binge-like drinking in head-fixed mice, we lay the groundwork for leveraging advanced microscopy technologies to study alcohol-induced neuroadaptations in PFC and other brain circuits.


Sources and influences of atmospheric nonpolar organic compounds in Nanchang, central China: Full-year monitoring with a focus on winter pollution episodes.
Nonpolar organic compounds (NPOCs) are found in atmospheric aerosols and have significant implications for environmental and human health. Although many studies have quantitatively estimated the sources of NPOCs in different cities, few have evaluated their main influencing factors (e.g., emissions and meteorological conditions) at relatively long (e.g., different seasons) and short timescales (e.g., several days during pollution episodes). A better understanding of this issue could optimise strategies for dealing with organic contamination in atmospheric particulate matter. NPOCs (including n-alkanes, PAHs and hopanes) in fine particulate matter (PM2.5) were sampled daily at Nanchang, China, from 1 November 2020 to 31 October 2021. Analyses of specific biomarkers and diagnostic ratios indicate that the NPOCs mainly had anthropogenic sources. The quantitative estimates of a positive matrix factorization model show that fossil fuel and biomass combustion were the main sources of n-alkanes (contributing 64.8 %), while vehicle exhaust was the main source of PAHs (47.0 %) and hopanes (52.3 %). Seasonally, the contributions from coal and/or biomass combustion were higher in autumn and winter (40.2-56.3 %) than in spring and summer (25.7-44.3 %), while contributions from natural plants, petroleum volatilization and vehicle exhaust were higher in spring and summer (14.7-63.5 %) than in autumn and winter (8.1-48.9 %). Redundancy analysis shows that increased emissions, especially from coal and/or biomass combustion, are the main cause of increases in NPOCs, during both annual sampling periods and winter pollution episodes. Over the year, higher temperature and longer sunshine hours correspond to lower NPOC concentrations. In winter pollution episodes, increases in temperature and relative humidity correspond to increases in NPOC concentrations. Our results suggest that controlling primary emissions, especially from coal and biomass combustion, may be an effective way to prevent increases in NPOC concentrations.


On the local optimality of the fuzzy isodata clustering algorithm.
The convergence of the fuzzy ISODATA clustering algorithm was proved by Bezdek [3]. Two sets of conditions were derived and it was conjectured that they are necessary and sufficient for a local minimum point. In this paper, we address this conjecture and explore the properties of the underlying optimization problem. The notions of reduced objective function and improving and feasible directions are used to examine this conjecture. Finally, based on the derived properties of the problem, a new stopping criterion for the fuzzy ISODATA algorithm is proposed.


Iatrogenic breaks in Buuch's membrane in choroidal melanoma.
Three patients with choroidal melanoma have been observed to develop subretinal hemorrhages associated with their ocular examinations. One hemorrhage appears to have been caused by transillumination, while two others have occurred during radioactive phosphorus testing. Histopathology confirms defects in Bruch's membrane through which blood or tumor cells have entered the subretinal space.


Innovative nuclear pharmacy service. A comprehensive management plan for clinical investigations.
To provide an overview of the investigational nuclear pharmacy service at the Medical University of South Carolina. References were selected from published bibliographies of nuclear pharmacy and hospital pharmacy articles and from specific-topic searches of the MEDLINE computerized database (all languages, through 1992). Studies of clinical pharmacy functions that were considered relevant to the specialty practice of nuclear pharmacy were chosen. Studies were reviewed for internal consistency and appropriateness. Data on the clinical impact of nuclear pharmacy services do not exist. Based on our experience in establishing an investigational drug service, we conclude that nuclear pharmacists should take an active role in clinical investigations. The outcomes of this kind of involvement are very rewarding.


Thrombotic microangiopathy and occult neoplasia.
Thrombotic thrombocytopenic purpura (TTP), which is typically characterized by fever and central nervous system manifestations and hemolytic uremic syndrome (HUS), in which renal failure is a prominent feature are the most common thrombotic microangiopathies (TMAs). TTP is usually associated with a severe deficiency of ADAMTS13 [a metalloproteinase involved in the degradation of von Willebrand factor (vWF) multimers], causing excessive accumulation of ultra-large vWF multimers and platelet aggregation with organ failure. By contrast, patients with HUS or other TMAs usually display a normal or at least detectable ADAMTS13 activity. A TMA may be occasionally developed in association with HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome, infections, cancer and bone marrow transplantation. In cancer patients, TMA may be related to chemotherapeutic regimens or the malignant disease itself. Occasionally, TMA is the first manifestation of an occult cancer, and in large series approximately 3% of patients who were originally diagnosed with TTP, were in fact harboring an occult malignancy. The pathogenesis of cancer-associated TMAs is not completely elucidated, but probably the most important factor is endothelial damage. However, cancer-associated TMAs show some distinct features that should promptly lead to complementary investigations for an underlying malignancy. Weakness, cough and dyspnoea, fever, weight loss, bone and abdominal pain are the most common presenting symptoms. Generally, biochemistry reveals markedly increased LDH levels, increased alkaline phosphatase and the blood smear shows erythromyelemia. Bone marrow biopsy is a valuable tool in order to establishing malignant seeding. Treatment of the underlying neoplasia is the mainstay of therapy and there is no role for plasmapheresis or plasma infusions.


A structural analysis of health outcomes after spinal cord injury.
To develop and validate a latent model of health outcomes among persons with spinal cord injury. Survey data were collected at a large specialty hospital in the southeastern USA from 1,388 adult participants with traumatic spinal cord injury of at least 1 year's duration. Multiple indicators of health outcomes were used, including general health ratings, days adversely affected by poor health and poor mental health, treatments and hospitalizations, depressive symptoms, symptoms of illness or infection (eg, sweats, chills, fever), and multiple individual conditions (eg, pressure ulcers, subsequent injuries, fractures, contractures). We performed exploratory factor analysis on half of the sample and confirmatory factor analysis on the other. A 6-factor solution was the best overall solution, because there was an excellent fit with the exploratory factor analysis (root mean square error of approximation = 0.042) and acceptable fit with the confirmatory factor analysis (root mean square error of approximation = 0.065). Four of the factors were types of secondary conditions, including symptoms of illness or infection, orthopedic conditions, pressure ulcers, and subsequent injuries. The 2 remaining factors reflected global health and treatment. Gender, race-ethnicity, age, injury severity, and years of education were all significantly related to at least 1 factor dimension, indicating variations in health outcomes related to these characteristics. Identification of the 6 factors represents an improvement over the utilization of multiple individual indicators, because composite scores generated from multiple individual indicators provide more informative and stable outcome scores than utilization of single indicators.


[Health resources and strategies: knowledge and practice of women living in poverty areas in Brazil].
This study presents a reflection on the health resources and strategies used by poor Brazilian women and that coexist with "official" medical practices. For this qualitative research, the authors applied social representation categories as central categories of analysis, which were understood as part of contradictory social relations and of the collective history of the groups. The peculiar way by which popular segments reaffirm and, at the same time, deny their own knowledge/action as a counterpoint to the dominant medical practices is brought into focus, beginning from the utilization of a varied set of health resources and strategies that include measures such as household-medicine, medical and religious practices, self-medication, consultations with "pharmacists" and orientation by local health agents.


[National external quality assessment in auto-immunity: autoantibodies detected on liver, kidney and stomach tissues].
In 2003, for the scheme of the French national external quality assessment, Afssaps organized for the first time a survey on auto-antibodies detected on liver, kidney and stomach tissues. This survey had two purposes: first to make an inventory of the methodology applied by the medical laboratories and secondly to assess the quality of the results. The survey sample contained M2 anti-mitochondrial antibodies. Overall results are satisfactory. Concerning the titer of antibodies, a broad dispersion of results was observed (12% of titers were upper than the expected titer). Delivered information to the participants, at the end of the survey, should improve analytical procedures applied by the biologists. An effort of standardization by using titrated internal controls would be suitable.


Bioactive luminescent transition-metal complexes for biomedical applications.
The serendipitous discovery of the anticancer drug cisplatin cemented medicinal inorganic chemistry as an independent discipline in the 1960s. Luminescent metal complexes have subsequently been widely applied for sensing, bio-imaging, and in organic light-emitting diode applications. Transition-metal complexes possess a variety of advantages that make them suitable as therapeutics and as luminescent probes for biomolecules. It is thus highly desirable to develop new luminescent metal complexes that either interact with DNA through different binding modes or target alternative cellular machinery such as proteins as well as to provide a more effective means of monitoring disease progression. In this Review, we highlight recent examples of biologically active luminescent metal complexes that can target and probe a specific biomolecule, and offer insights into the future potential of these compounds for the investigation and treatment of human diseases.


Short-term effects of fertilization on photosynthesis and leaf morphology of field-grown loblolly pine following long-term exposure to elevated CO(2) concentration.
We examined effects of a first nitrogen (N) fertilizer application on upper-canopy needle morphology and gas exchange in approximately 20-m-tall loblolly pine (Pinus taeda L.) exposed to elevated carbon dioxide concentration ([CO(2)]) for 9 years. Duke Forest free-air CO(2) enrichment (FACE) plots were split and half of each ring fertilized with 112 kg ha(-1) elemental N applied in two applications in March and April 2005. Measurements of needle length (L), mass per unit area (LMA), N concentration (N(l)) on a mass and an area basis, light-saturated net photosynthesis per unit leaf area (A(a)) and per unit mass (A(m)), and leaf conductance (g(L)) began after the second fertilizer application in existing 1-year-old foliage (F(O)) and later in developing current-year first-flush (F(C1)) and current-year second-flush (F(C2)) foliage. Elevated [CO(2)] increased A(a) by 43 and 52% in F(O) and F(C1) foliage, respectively, but generally had no significant effect on any other parameter. Fertilization had little or no significant effect on L, LMA, A or g(L) in F(O) foliage; although N(l) was significantly higher in fertilized trees by midsummer. In contrast, fertilization resulted in large increases in L, N(l), and A in F(C1) and F(C2) foliage, increasing A(a) by about 20%. These results suggest that, although both needle age classes accumulate N following fertilization, they use it differently-current-year foliage incorporates N into photosynthetic machinery, whereas 1-year-old foliage serves as an N store. There were no significant interaction effects of elevated [CO(2)] and fertilization on A. Elevated [CO(2)] increased the intercept of the A:N(l) relationship but did not significantly affect the slope of the relationship in either foliage age class.


[Functional duality of kinin receptors in pathophysiology].
Kinins are autacoid peptides and central neuromediators involved in cardiovascular regulation, inflammation and pain. Their effects are mediated by two transmembrane G-protein-coupled receptors denoted as B1 and B2. While the B2 receptor is constitutive, the B1 receptor is inducible and up-regulated in the presence of cytokines, endotoxins or during tissue injury. The B2 receptor is believed to play an important role in the beneficial effects of angiotensin-1 converting enzyme inhibitors used in the treatment of cardiovascular diseases, yet it is involved in the acute phase of inflammation and of somatic and visceral pain. Conversely, the B1 receptor participates in the chronic phase of these responses and is likely to play a strategic role in diseases with a strong immune component such as rheumatoid arthritis, multiple sclerosis, septic shock and diabetes. A dual function for the B1 receptor is also reported in some pathologies in which it can exert either a protective (multiple sclerosis and septic shock) or harmful (pain and inflammation) effect. Therefore, the use of antagonists for these receptors as clinical therapeutic agents requires a rigorous evaluation of the potential side effects.


Mutagenesis and crystallographic studies of Zymomonas mobilis tRNA-guanine transglycosylase reveal aspartate 102 as the active site nucleophile.
Procaryotic tRNA-guanine transglycosylase (TGT) catalyzes the posttranscriptional base exchange of the queuine precursor 7-aminomethyl-7-deazaguanine (preQ1) with the genetically encoded guanine at the wobble position of tRNAs specific for Asn, Asp, His, and Tyr. The X-ray structures of Zymomonas mobilis TGT and of its complex with preQ1 [Romier, C., Reuter, K., Suck, D., & Ficner, R. (1996) EMBO J. 15, 2850-2857] have revealed a specific preQ1 binding pocket and allowed a proposal for tRNA binding and recognition. We have used band-shift experiments in denaturing conditions to study the enzymatic reaction performed by TGT. The presence of shifted protein bands after incubation with tRNA followed by protein denaturation indicates a reaction mechanism involving a covalent intermediate. Inspection of the X-ray structures and comparison of the different procaryotic TGT sequences highlighted the conserved aspartate 102 as the most likely nucleophile. Mutation of this residue into alanine by site-directed mutagenesis leads to an inactive mutant unable to form a covalent intermediate with tRNA, proving that aspartate 102 is the active site nucleophile in TGT. To investigate the recognition of the wobble guanine in the preQ1 binding pocket, we mutated aspartate 156, the major recognition element for preQ1, into alanine and tyrosine. Both mutants are inactive in producing the final product, but the mutant D156A is able to form the covalent intermediate with tRNA in the first step of the reaction mechanism in comparable amounts to wild-type protein. Therefore, the binding of the wobble guanine in the preQ1 binding pocket is required for the cleavage of the glycosidic bond. The three mutants were crystallized and their X-ray structures determined. The mutants display only subtle changes to the wild-type protein, confirming that the observed biochemical results are due to the chemical substitutions rather than structural rearrangements.


Characteristics of acute adult poisoning cases admitted to a university hospital in Istanbul.
The aim of this retrospective study was to analyse the characteristics of acute adult poisoning cases admitted to a university hospital in Istanbul, Turkey. All cases admitted to the Emergency Unit of the Istanbul University Cerrahpaşa Medical Faculty Hospital, between January 2001 and December 2001, were included in this study. We analysed the clinical charts for aetiological and demographical characteristics of the acutely poisoned patients. There were 284 poisoning cases (207 females and 77 males) among 11834 patients admitted to the Emergency Unit. This was 2.4% of all emergency admissions. The female-to-male ratio was 3:1. The mean age was 27+/-12 years (age range 15-87) and the majority of the patients (73.94%) were below the age of 30 years. The median age was 24 years. Medicinal drugs were the major cause (69.37%) of the cases, followed by inhalation of gases (14.44%), alcohol (5.99%), alcohol together with illicit drugs (4.23%), food (3.17%), corrosives (1.76%) and pesticides (1.06%). The route of administration was as follows: 84.51% orally, 14.44% by inhalation and 1.06% by intravenous injection. Seventy-one per cent of acute poisonings were self-inflicted and 88% occurred at home. The most frequently involved medicinal drugs were antidepressants and analgesics. In 32.04% of cases, there was more than one medicinal drug responsible for the poisoning. The seasonal distribution in poisoning patients suggested a peak in summer (31.7% of presentations) and winter (30.9%) and lower numbers in spring (22.9%) and autumn (14.5%). The follow-up period of the patients were 1-12 hours for 42 cases (15%), 13-24 hours for 134 cases (47%) and more than 24 hours for 108 cases (38%). Two of the 284 cases with acute poisonings were fatal. This was a university hospital-based study, so these results may not be representative of the general population. Despite this drawback, these data still provide important information about the characteristics of poisoning in the largest city of the country. cn


Single and Combined Effects of Chlorpyrifos and Glyphosate on the Brain of Common Carp: Based on Biochemical and Molecular Perspective.
Chlorpyrifos (CPF) and glyphosate (GLY) are the most widely used organophosphate insecticide and herbicide worldwide, respectively; co-occurrence of CPF and GLY in aquatic environments occurs where they inevitably have potential hazards to fish. However, the potential mechanisms of CPF and GLY to induce toxicity have not been fully explored. To identify the adverse impacts of CPF and GLY on fish, either alone or in combination (MIX), CPF (25 μg/L) and GLY (3.5 mg/L) were set up according to an environmentally relevant concentration to expose to common carp for 21 days. After exposure, CPF and GLY decreased the activities of acetylcholinesterase and Na+/K+-ATPase, altered monoamine oxidase levels, decreased antioxidant enzyme activities (superoxide dismutase, catalase, glutathione S-transferase and glutamic reductase), and induced the accumulation of malondialdehyde in the carp brain. The parameters in the MIX groups had a greater impact compared to that in the CPF or GLY group, suggesting that both single and combined exposure could affect neurological signaling systems and cause oxidative stress and lipid peroxidation damage in carp brains, and that MIX exposure increases the impact of each pollutant. RNA-seq results showed that single or combined exposure to CPF and GLY induced global transcriptomic changes in fish brains, and the number of differentially expressed genes in MIX-treated carp brains were globally increased compared to either the CPF or GLY groups, suggesting that the effects of co-exposure were greater than single exposure. Further analysis results revealed that the global transcriptomic changes participated in oxidative stress, immune dysfunction, and apoptosis of fish brains, and identified that the P13k-Akt signaling pathway participates in both single and combined exposure of CPF- and GLY-induced toxicity. Taken together, our results demonstrated that the interaction of CPF and GLY might be synergic and provided novel insights into the molecular mechanisms of fish brains coping with CPF and GLY.


Photodetachment of deprotonated aromatic amino acids: stability of the dehydrogenated radical depends on the deprotonation site.
While aromatic amino acids in their deprotonated form have been well characterized by IR and photoelectron spectroscopies, no information is available on the neutral dehydrogenated radicals and, in particular, on their stability when the deprotonation site is changed. This is investigated by observing the neutral fragment issued from either simple photodetachment or dissociative photodetachment of the deprotonated aromatic amino acids phenylalanine, tyrosine, and tryptophan. We show that the dehydrogenated radicals of aromatic amino acids produced upon photodetachment of molecules deprotonated on the carbonyl group dissociate without barrier, leading to the formation of CO2 and a radical amine. However, when the system is deprotonated on functional groups located on the chromophore, the radicals produced by photodetachment are stable, indicating the important photostabilizing role played by functional groups.


Structural and functional analysis of the minimal orthomyxovirus-like polymerase of Tilapia Lake Virus from the highly diverged Amnoonviridae family.
Tilapia Lake Virus (TiLV), a recently discovered pathogen of tilapia fish, belongs to the Amnoonviridae family from the Articulavirales order. Its ten genome segments have characteristic conserved ends and encode proteins with no known homologues, apart from the segment 1, which encodes an orthomyxo-like RNA-dependent-RNA polymerase core subunit. Here we show that segments 1-3 encode respectively the PB1, PB2 and PA-like subunits of an active heterotrimeric polymerase that maintains all domains found in the distantly related influenza polymerase, despite an unprecedented overall size reduction of 40%. Multiple high-resolution cryo-EM structures of TiLV polymerase in pre-initiation, initiation and active elongation states, show how it binds the vRNA and cRNA promoters and performs RNA synthesis, with both transcriptase and replicase configurations being characterised. However, the highly truncated endonuclease-like domain appears inactive and the putative cap-binding domain is autoinhibited, emphasising that many functional aspects of TiLV polymerase remain to be elucidated.


A novel two-dimensional polyacrylamide-gel pattern, which may be due to allelic genes, of phenylalanine hydroxylase in monkeys.
Two-dimensional gel electrophoresis of immunopurified monkey liver phenylalanine hydroxylase showed a novel form of the enzyme, in 4 out of 24 monkeys, in which each polypeptide spot was split into a doublet with the same charge but slightly different mobility in the sodium dodecyl sulphate/polyacrylamide-gel-electrophoresis (as opposed to the isoelectric-focusing) dimension. Phenylalanine hydroxylase formed by translation of RNA from a liver containing the novel form showed the doublet pattern, suggesting that it is due to differences in mRNA. By analogy with the rat, this mRNA difference could be due to allelic genes.


Properties of pig synovial collagenase.
1. Properties of a purified chemically activated form of pig synovial collagenase were examined and compared with a spontaneously active form of the enzyme. 2. The active enzyme has a specific activity of 53 000 units (microgram/min)/mg, a mol.wt. of 44 000 (by sodium dodecyl sulphate/polyarcylamide-gel electrophoresis in 2-mercaptoethanol) and pI 5.2 (by isoelectric focusing in polyacrylamide gels). 3. The activity has the characteristics of a metalloproteinase that degrades types I and III soluble or insoluble collagens in preference to type II, at an optimum pH of 6.5-8.5. 4. There is no detectable difference in these properties between the chemically activated and spontaneously active form of collagenase.


Telomerase-associated protein TEP1 is not essential for telomerase activity or telomere length maintenance in vivo.
TEP1 is a mammalian telomerase-associated protein with similarity to the Tetrahymena telomerase protein p80. Like p80, TEP1 is associated with telomerase activity and the telomerase reverse transcriptase, and it specifically interacts with the telomerase RNA. To determine the role of mTep1 in telomerase function in vivo, we generated mouse embryonic stem (ES) cells and mice lacking mTep1. The mTep1-deficient (mTep1(-/-)) mice were viable and were bred for seven successive generations with no obvious phenotypic abnormalities. All murine tissues from mTep1(-/-) mice possessed a level of telomerase activity comparable to that in wild-type mice. In addition, analysis of several tissues that normally lack telomerase activity revealed no reactivation of telomerase activity in mTep1(-/-) mice. Telomere length, even in later generations of mTep1(-/-) mice, was equivalent to that in wild-type animals. ES cells deficient in mTep1 also showed no detectable alteration in telomerase activity or telomere length with increased passage in culture. Thus, mTep1 appears to be completely dispensable for telomerase function in vivo. Recently, TEP1 has been identified within a second ribonucleoprotein (RNP) complex, the vault particle. TEP1 can also specifically bind to a small RNA, vRNA, which is associated with the vault particle and is unrelated in sequence to mammalian telomerase RNA. These results reveal that TEP1 is an RNA binding protein that is not restricted to the telomerase complex and that TEP1 plays a redundant role in the assembly or localization of the telomerase RNP in vivo.


Comparing peer education with TBL workshop in (EBM) teaching.
Background: Evidence-based medicine is one of the most important topics in medical sciences that requires a proper teaching method. Very few studies have evaluated EBM education outcomes through peers and TBL workshops. The purpose of this study was to compare the effect of evidence-based medicine (EBM) education through peers with TBL workshop method in medical students. Methods: This quasi-experimental study was conducted on 42 medical students of the Faculty of Medicine in Iran University of Medical Sciences (IUMS) in 2019 who were selected through convenience sampling. Students were divided into 2 experimental and control groups based on the randomized blocking method. The data collection tools were 2 questioners that evaluated EBM knowledge and satisfaction in both intervention and control groups. The knowledge of students was compared using pretest and posttest and their satisfaction was evaluated at the end of the TBL workshop and peer education. Data were analyzed by SPSS software and descriptive tests (t test and ANOVA), and significance level was set at 0.95. Results: A significant difference was found between the level of basic knowledge (pretest) and secondary knowledge (posttest) in the EBM education through TBL workshop method compared to peer method. The average scores gained by students in TBL workshop were 3.8 more than the peer teaching method. The results of the Satisfaction Questionnaire were 74% in control group and 86% in the experimental group. Conclusion: EBM education through TBL workshop both increased students' knowledge and satisfaction compared to peer education. Thus, it can be concluded that providing EBM education by expert and qualified teachers through face to face teaching strategy can be effective in knowledge translation. However, peers can participate in educational sessions as facilitators.


Evaluating the impact of telepharmacy.
The impact of remote pharmacist review of medication orders in three small community hospitals in California was evaluated. A longitudinal study was conducted in three community hospitals without 24-hour pharmacy services before and after the implementation of telepharmacy services. Override reports from automated dispensing cabinets were reviewed. Charts were reviewed for errors and potential adverse drug events. Pharmacist interventions during times when the pharmacy was closed were evaluated. Cost estimates were based on a proprietary intervention tracking program. Surveys were administered to staff nurses and pharmacists to assess concerns about medication-use safety and job satisfaction. The number of times that nurses obtained and administered medications without pharmacist review declined by 35.3% after implementation of the telepharmacy service. There was a significant reduction in the percentage of high-risk medications obtained without a pharmacist review. Three potential adverse drug events were discovered before implementing remote order review versus none in the postimplementation period. The number of pharmacist interventions increased from 15 to 98 per week after implementing remote order review by pharmacists. Estimated cost savings resulting from preventing, identifying, and resolving medication-related problems were $261,109 per hospital in total cost saved or avoided. Nurses' survey scores reflected increased comfort with the medication-use system, patient safety, and job satisfaction. Remote review of medication orders by pharmacists when the hospital pharmacy was closed decreased the number of potential adverse drug events reported and improved job satisfaction among nurses.


Validation of the Delirium Diagnostic Tool-Provisional (DDT-Pro) With Medical Inpatients and Comparison With the Confusion Assessment Method Algorithm.
Delirium remains underdetected as a result of its broad constellation of symptoms and the inadequate neuropsychiatric expertise of most medical-surgical clinicians. Brief, accurate tools are needed to enhance detection. The authors extended validation of the Delirium Diagnostic Tool-Provisional (DDT-Pro), originally validated in a study of inpatients with traumatic brain injury for diagnosis of delirium by nonexpert clinicians, for 200 general medical inpatients in Colombia. The three structured, quantitatively rated items in DDT-Pro represent the three core delirium domains. High interrater reliability between physician and nurse (0.873) administrators, internal consistency (>0.81), and content validity were found. Compared with independent reference standard diagnosis with DSM-5 or the Delirium Rating Scale-Revised-98, the area under the receiver operating characteristic (ROC) curve (global diagnostic accuracy) range was 93.8%-96.3%. ROC analysis revealed the same cutoff score (≤6) as that for the original study, with somewhat lower sensitivities of 88.0%-90.0% and specificities of 85.3%-81.2% (independent expert physician or nurse ratings). Even when rated by a trained expert physician, the original version of the Confusion Assessment Method algorithm (CAM-A) performed moderately, with lower sensitivities (61.8%-70.0%) than the DDT-Pro (88.0%-100%) and somewhat higher specificities (84.8%-95.3% versus 67.4%-86.7%), with values depending on dementia status, reference standard, and rater type. Accuracies for the DDT-Pro and CAM-A were comparable (DDT-Pro: 83.0%-87.5% versus CAM-A: 87.5%-88.5%), although lower in the dementia subgroup, especially for CAM-A. However, these tools were significantly discordant, especially in negative cases, which suggests that they do not detect diagnosis of patients in the same way. The DDT-Pro had high validity and reliability in provisional delirium diagnosis by physicians and nonexpert clinicians, although further validation is warranted before widespread use can be recommended.


Chemotherapy for prostate carcinoma.
We have evaluated the role of chemotherapy for the treatment of prostate carcinoma. The data of patients with endocrine-resistant stage D2 disease indicate that clinical benefits in such patients are at best marginal. Despite the controversies involved in the assessment of response in this disease, in this review we show that in over 3,000 patients eligible for evaluation, less than 10% had complete or partial responses to various treatment regimens. Survival evaluation on all prospective randomized clinical trials showed no advantages in favor of any treatment tested and, moreover, in 2 of such studies involving various single agents, survival was not better than a "no chemotherapy" control arm. Because of these data, we conclude that chemotherapy is not indicated as an adjuvant treatment for patients with localized prostate cancer. Although patients with prostate cancer frequently respond to androgen deprivation procedures, preclinical and clinical data strongly suggest the existence of endocrine-independent cell clones, which supports further testing with nonhormonal cytotoxic treatment. A close multidisciplinary interaction is a prerequisite for development of new effective systemic treatment in this disease.


[Prevalence of Candida albicans and Candida non-albicans in clinical samples during 1999-2001].
The importance of epidemiological monitoring of yeasts involved in pathologic processes is unquestionable due to the increase of these infections over the last decade, the changes observed in species causing candidiasis, and empirical antifungal treatment. At the Mycology Center, 1006 isolates from a wide range of clinical samples were studied during 1999-2001. Candida albicans (40.3%) was the most isolated species, although, the Candida no albicans species with 54.9% showed the major prevalence. In blood cultures Candida parapsilosis (34.9%), C. albicans (30.2%) and C. tropicalis (25.6%) were recovered most frequently while C. glabrata represented only 2.3%. C. albicans with 60%-80% was the predominant specie in mucosal surface. We also detected Candida mediastinistis, which alert us over the importance at this location. Urinary tract infections caused by yeasts were more frequent in hospitalized patients, being C. albicans (47.7%), the most commonly isolated, followed by C. glabrata (24.8%) and C. tropicalis (20.0%). In the candidal onychomycoses, C. parapsilosis (37.7%) outplaced C. albicans (22.0%). Fluconazole susceptibility studies of Candida species allowed us to conclude that the majority of C. albicans islolates are susceptible, and that the highest resistance averages were observed in C. glabrata (21.41%) and C. krusei (69.23%).


Self-monitoring enhances Wisconsin Card Sorting Test performance in patients with schizophrenia: performance is improved by simply asking patients to verbalize their sorting strategy.
Patients with schizophrenia have Wisconsin Card Sorting Test (WCST) deficits, which are commonly interpreted as reflecting frontal cortex-based executive dysfunction. One means of assessing the refractoriness of frontal-executive impairment is to utilize a training or modification strategy to improve WCST performance. In this study, 73 patients with schizophrenia were assigned to 1 of 2 groups. Group 1 received the standard WCST instructions for 64 cards (Condition 1). For the second 64-card deck, the patients were asked to verbalize the reason that they placed the card where they did after each sort (Condition 2). Group 2 received this modified instruction 1st (Condition 1) and then the standard instructions for the second deck (Condition 2). A group of normal comparison participants was also tested using standard instructions alone. Group 2 committed significantly fewer perseverative responses than did Group 1. Furthermore, there was no significant difference between Group 2 (Condition 1) and the normal participants. Group 1's performance improved when patients were exposed to the modified instructions (Condition 2). Additionally, poor premorbid factors and disorganized symptoms were associated with decreased benefit from the modified instructions across both groups. Cumulatively, these data suggest that a simple instruction may enhance executive function and impact WCST performance in patients with schizophrenia.


A potential broad-spectrum neutralizing antibody against Betacoronavirus.
Three pandemics caused by human Betacoronavirus had broken out in the past two decades. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was one of the novel epidemic strains which caused the third pandemic, coronavirus disease 2019 (COVID-19), a global public health crisis. So far, more than millions of people have been infected. Considering the public health and economic impact of Betacoronavirus pandemic, drugs with broad-spectrum activity against these coronaviruses are urgently needed. In this study, two monoclonal antibodies targeting SARS-CoV-2 spike protein receptor-binding domain (RBD) with good neutralizing activity were used to construct a novel immunoglobulin-like bispecific antibody BI31. The neutralizing effect of BI31 against the pseudovirus and the authentic virus is better than that of its parent antibodies alone and in combination. What surprised us most was that the newly constructed bispecific antibody also had the neutralizing activity against SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) that the parent antibodies did not have. These suggested that the BI31 can not only be developed as a therapeutic drug against COVID-19 but it could also become a broad-spectrum therapeutic antibody against Betacoronavirus.


Block of sodium channels in planar lipid bilayers by guanidium toxins and calcium. Are the mechanisms of voltage dependence the same?
The block of single, batrachotoxin-activated sodium channels by saxitoxin (STX), tetrodotoxin (TTX), and Ca2+ has been investigated in planar bilayers. All three substances block in a voltage-dependent manner with hyperpolarizing potentials favoring block. Extracellular Ca2+ competitively inhibits binding of STX and relieves STX block. Trimethyloxonium, a carboxyl-methylating agent, eliminates block by STX and TTX and dramatically reduces block by Ca2+. These results suggest that STX, TTX, and Ca2+ compete for a negative site on the outside of the channel. The voltage dependence of block by STX (divalent cation) and TTX (monovalent) was similar (40 mV/e-fold), suggesting that voltage dependence is due to a conformational change in the channel rather than to the toxins entering the membrane electric field to block. A physical model, with an external binding site for toxins and Ca2+ and another site deeper within the electric field (associated with the "selectivity filter") that is accessible to Ca2+ but not toxins, predicts voltage-dependence Ca2+ block without invoking the conformational change needed to explain the voltage dependence of block by TTX and STX.


A new structural state of myosin.
The mechanism by which motor proteins hydrolyze ATP and move along cytoskeletal filaments is still unknown. One approach to deciphering the mechanism is to correlate steps of ATP hydrolysis with structural states of the motors to determine the changes the motors undergo during the hydrolysis cycle. Unfortunately, available crystal structures represent only a few steps of the cycle and obtaining atomic structures that represent the motors bound to their filament has been difficult. Now, two new myosin crystal structures have been reported that show features expected for myosin motors bound in rigor to actin. The two new structures show changes at both the actin-binding surface and the active site that have not been observed previously.


Fusarium Keratitis in Germany.
Fusarium keratitis is a destructive eye infection that is difficult to treat and results in poor outcome. In tropical and subtropical areas, the infection is relatively common and associated with trauma or chronic eye diseases. However, in recent years, an increased incidence has been reported in temperate climate regions. At the German National Reference Center, we have observed a steady increase in case numbers since 2014. Here, we present the first German case series of eye infections with Fusarium species. We identified Fusarium isolates from the eye or eye-related material from 22 patients in 2014 and 2015. Thirteen isolates belonged to the Fusarium solani species complex (FSSC), 6 isolates belonged to the Fusarium oxysporum species complex (FOSC), and three isolates belonged to the Fusarium fujikuroi species complex (FFSC). FSSC was isolated in 13 of 15 (85%) definite infections and FOSC in 3 of 4 (75%) definite contaminations. Furthermore, diagnosis from contact lens swabs or a culture of contact lens solution turned out to be highly unreliable. FSSC isolates differed from FOSC and FFSC by a distinctly higher MIC for terbinafine. Outcome was often adverse, with 10 patients requiring keratoplasty or enucleation. The use of natamycin as the most effective agent against keratitis caused by filamentous fungi was rare in Germany, possibly due to restricted availability. Keratitis caused by Fusarium spp. (usually FSSC) appears to be a relevant clinical problem in Germany, with the use of contact lenses as the predominant risk factor. Its outcome is often adverse.


Influence of vmPFC on dmPFC Predicts Valence-Guided Belief Formation.
When updating beliefs about their future prospects, people tend to disregard bad news. By combining fMRI with computational and dynamic causal modeling, we identified neurocircuitry mechanisms underlying this optimism bias to test for valence-guided belief formation. In each trial of the fMRI task, participants (n = 24, 10 male) estimated the base rate (eBR) and their risks of experiencing negative future events, were confronted with the actual BR, and finally had the opportunity to update their initial self-related risk estimate. We demonstrated an optimism bias by revealing greater belief updates in response to good over bad news (i.e., learning that the actual BR is lower or higher than expected) while controlling for confounds (estimation error and personal relevance of the new information). Updating was favorable when the final belief about risks improved (or at least did not worsen) relative to the initial risk estimate. This valence of updating was encoded by the ventromedial prefrontal cortex (vmPFC) associated with the valuation of rewards. Within the updating circuit, the vmPFC filtered the incoming signal in a valence-dependent manner and influenced the dorsomedial prefrontal cortex (dmPFC). Both the valence-encoding activity in the vmPFC and its influence on the dmPFC predicted individual magnitudes of the optimism bias. Our results indicate that updating was biased by the motivation to maximize desirable beliefs, mediated by the influence of the valuation system on further cognitive processing. Therefore, although it provides the very basis for human reasoning, belief formation is essentially distorted to promote desired conclusions.SIGNIFICANCE STATEMENT The question of whether human reasoning is biased by desires and goals is crucial for everyday social, professional, and economic decisions. How much our belief formation is influenced by what we want to believe is, however, still debated. Our study confirms that belief updates are indeed optimistically biased. Critically, the bias depends on the recruitment of the brain valuation system and the influence of this system on neural regions involved in reasoning. These neurocircuit interactions support the notion that the motivation to maximize pleasant beliefs reinforces those cognitive processes that are most likely to yield the desired conclusion.


The Faden operation. When and how to do it.
The Faden operation (posterior fixation of a muscle) creates an artificial palsy. With this tool the eye surgeon can solve problems concerning palsies, nystagmic amblyopia, and many cases of head posture. Changing angles in children with congenital strabismus can be stabilized by bilateral Faden operations on the medial rectus. The results are given of a retrospective analysis of nearly 400 cases operated 3 years ago. The paper deals with some of the technical problems and ends with some remarks on postoperative motility after Faden operations.


Developments in Antibacterial Therapy: Focus on Physical Stimuli Approaches.
At present, various antibacterial therapeutic modalities are available in the clinic. However, due to the rampant abuse of antibiotics over the past few decades and the consequent emergence of innumerable drug-resistant strains of bacteria, it is imperative to develop new and effective antibacterial therapeutic strategies. In recent years, the physical stimuli-based approach to antibacterial therapy has aroused much interest as an alternative to antibiotics and has become a major focus of antibacterial research. In this review, the application of different physical stimuli, including electricity, magnetism, light, ultrasound and thermal stimulation, in antibacterial research is critically examined in order to provide new ideas and directions for the further development of antibacterial therapy in clinical dentistry.


Association of FLOWERING LOCUS T/TERMINAL FLOWER 1-like gene FTL2 expression with growth rhythm in Scots pine (Pinus sylvestris).
Understanding the genetic basis of the timing of bud set, an important trait in conifers, is relevant for adaptation and forestry practice. In common garden experiments, both Scots pine (Pinus sylvestris) and Norway spruce (Picea abies) show a latitudinal cline in the trait. We compared the regulation of their bud set biology by examining the expression of PsFTL2, a Pinus sylvestris homolog to PaFTL2, a FLOWERING LOCUS T/TERMINAL FLOWER 1 (FT/TFL1)-like gene, the expression levels of which have been found previously to be associated with the timing of bud set in Norway spruce. In a common garden study, we analyzed the relationship of bud phenology under natural and artificial photoperiods and the expression of PsFTL2 in a set of Scots pine populations from different latitudes. The expression of PsFTL2 increased in the needles preceding bud set and decreased during bud burst. In the northernmost population, even short night periods were efficient to trigger this expression, which also increased earlier under all photoperiodic regimes compared with the southern populations. Despite the different biology, with few limitations, the two conifers that diverged 140 million yr ago probably share an association of FTL2 with bud set, pointing to a common mechanism for the timing of growth cessation in conifers.


Sun-protection and sun-exposure habits among sailors: results of the 2018 world's largest sailing race Barcolana' skin cancer prevention campaign.
Epidemiologic data suggest an increased risk of melanoma (MM) and non-melanoma skin cancer (NMSC) in persons with intense recreational sun-exposure such as marathon runners or surfers. Up to data little is known about the sun-exposure habits, sun-protection behaviours and risk factors for MM and NMSC among sailors. The objective of this prospective, cross-sectional study was to investigate the sun-exposure and sun-protective habits and risk factors for skin cancer among sailors attending the 50° edition of Barcolana, the largest sailing race in of the world, which took place in October 2018 in Trieste, Italy as an integrative component of a public sun-prevention campaign. The study consisted of 2 parts: (i) a self-administered questionnaire focusing on sun-exposure and protective habits and (ii) a free skin examination carried out by volunteer dermatologists. Participation was optional and anonymous, and open to visitors and sailors attending the event. Overall, 431 (52.4%) sailors and 391 (47.6%) visitors responded to the questionnaire, while a total of 437 individuals including 189 (43.3%) sailors and 248 (56.6%) visitors participated in the skin examination group. The majority of sailors reported a past history of severe sunburns (20.2%), applied sunscreen never (14.4%) to sometimes (45.7%) or only once daily (59%) on the face (55%) and shoulders (26%). Moreover, 14% of sailors had a personal history of non-melanoma skin cancer (NMSC). During the dermatological examination, suspicious lesions for skin cancer (including MM and NMSC) were identified in 37% of the sailors. Our findings support the need to develop and promote primary and secondary prevention strategies to improve the sun-exposure and sun-protective habits among sailors.


Immunomodulatory effects of two silymarin isomers in a Balb/c mouse model of allergic asthma.
Allergic asthma is a complex chronic disease of the respiratory system presenting with cough, dyspnea, wheezing and airway obstruction. More than 300 million people of all age spectrums suffer from asthma worldwide. Immunological and inflammatory processes are main contributors to asthma. Cytokines produced by T helper 2 lymphocytes play main roles in asthma development and progression. Silymarin, a therapeutic agent with anti-oxidative properties, is a main component of Silybium marinum. We herein aimed to compare the anti-inflammatory and anti-allergic effects of two silymarin isomers, isosilybin A and silydianin, in the treatment of allergic asthma. After isolating and purifying isosilybin A and silydianin, Balb/c mouse model of allergic asthma was produced using ovalbumin injection. Seventy mice were categorized into five (1 normal and 4 asthmatic) groups (n = 14 per group). Mice in three of four asthmatic groups were treated with either isosilybin A, silydianin or budesonide. The 4th asthmatic group was used as positive control, with the non-asthmatic group serving as negative control. Airway hyperresponsiveness (AHR) and levels of IL-4, IL-5 and IL-13 in the BAL fluid were determined. Gene expressions of IL-4, IL-5, IL-13 and MUC5ac, as well as IgE serum level were also measured. Cellular composition of BAL fluid and lungs histopathology were finally investigated. Isosilybin A and silydianin reduced eosinophilic infiltration of lungs, IL-4 and IL-5 levels in BAL fluid, IL-4 and IL-5 gene expressions, as well as AHR in Balb/c mouse model of asthma. However, no significant changes were observed in IL-13 level and mucus hyper-secretion. According to our study, isosilybin A and silydianin can control main symptoms of asthma by modulating immune responses.


Impact of a multidisciplinary tumour board meeting for upper-GI malignancies on clinical decision making: a prospective cohort study.
The Dutch guidelines for diagnosis and treatment of upper-GI malignancies recommend review of patients by a multidisciplinary tumour board (MDT). The purpose of this study was to determine the effect on clinical decision making of an MDT for patients with upper-GI malignancies. All physicians participating in the MDT completed an electronic standardised case form to delineate their proposed treatment plan for the patients they presented, including the intent of treatment and the modality of treatment. This therapeutic or diagnostic proposal was then compared with the plan on which consensus was reached by the MDT. A total of 252/280 (90.0%) forms were completed and suitable for analysis. In 87/252 (34.5%) of the case presentations, the MDT altered the proposed plan of management. In 29/87 (33.3%) cases, a more extensive diagnostic work-up was decided upon. In 8/87 (9.2%) cases the curative intent of the proposed treatment was altered to palliation only. In 2/75 (2.7%) cases, however, it was decided that a patient could be treated with curative intent instead of the proposed palliative intent. In over 1/3 of cases, the diagnostic work-up or treatment plan is altered after evaluation by a multidisciplinary tumour board. This study supports Dutch guidelines recommending discussion of patients with upper-GI malignancies by a multidisciplinary tumour board.


Antigenic composition of Litomosoides carini.
Three different phosphate buffered saline extracts of Litomosoides carini were prepared and examined by gel diffusion, immunoelectrophoresis and disc polyacrylamide gel electrophoresis using sera from infected cotton rats and antisera from hyperimmunized rabbits. Using disc polyacrylamide gel electrophoresis, up to 22 protein, 6 lipoprotein and 4 glycoprotein bands were identified. A minimum of 8 precipitin lines were detected by gel diffusion and a maximum of 11 precipitin arcs by immunoelectrophoresis when pooled rabbit antiserum was used. Using infected cotton rat sera, fewer number of precipitin lines and arcs were detected. Two precipitin arcs did not have a counterpart on examination against pooled rabbit antiserum. The importance of these two specific antigenic components for use in immunodiagnosis of human filariasis has been discussed.


Symptomatic Remission and Counterfactual Reasoning in Schizophrenia.
Counterfactual thinking (CFT) is a type of conditional reasoning involving mental representations of alternatives to past factual events that previous preliminary research has suggested to be impaired in schizophrenia. However, despite the potential impact of these deficits on the functional outcome of these patients, studies examining the role of CFT in this disorder are still few in number. The present study aimed to extent previous results by evaluating CFT in the largest sample to date of schizophrenia patients in symptomatic remission and healthy controls. The relationship with symptomatology, illness duration, and sociodemographic characteristics was also explored. Methods: Seventy-eight schizophrenia patients and 84 healthy controls completed a series of tests that examined the generation of counterfactual thoughts, the influence of the "causal order effect," and the ability to counterfactually derive inferences by using de Counterfactual Inference Test. Results: Compared with controls, patients generated fewer counterfactual thoughts when faced with a simulated scenario. This deficit was negatively related to scores on all dimensions of the Positive and Negative Syndrome Scale-PANNS, as well as to longer illness duration. The results also showed that schizophrenia patients deviated significantly from the normative pattern when generating inferences from CFT. Conclusions: These findings reveal CFT impairment to be present in schizophrenia even when patients are in symptomatic remission. However, symptomatology and illness duration may have a negative influence on these patients' ability to generate counterfactual thoughts. The results might support the relevance of targeting CFT in future treatment approaches, although further research is needed to better describe the relationship between CFT and both symptomatology and functional outcome.


Feasibility of Conducting Autism Biomarker Research in the Clinical Setting.
Recruitment and completion of research activities during regular clinical care has the potential to increase research participation in complex neurodevelopmental disorders. We evaluated the feasibility, and effect on clinical care, of conducting biomarker research within a subspecialty clinical visit for autism spectrum disorder (ASD). Children, aged 5 to 10 years, were recruited by providers in ASD clinics at 5 institutions. Biomarkers collected were growth measurements, head circumference, neurologic and dysmorphology examinations, digit ratio (2D:4D) measurement, and platelet serotonin and urinary melatonin sulfate excretion levels. Parents completed the Aberrant Behavior Checklist-Community and a medical/demographic questionnaire. Cognitive level was abstracted from the medical record. Parents and clinicians completed surveys on the effect of the study on the clinical visit. Eighty-three children and their caregivers participated. Factors limiting participation included difficulty reaching families by phone and parent concern about the study blood draw requirement. All children completed at least 4 of 7 planned research activities. Demographic factors, educational placement, and child behavior were not associated with completion of study activities. Lower nonverbal cognitive function was weakly associated with fewer activities completed. Forty-four percent of clinicians reported an effect of the research study on the clinical visit. However, neither parent-reported nor clinician-reported effect was associated with the degree of study activity completion. Recruiting study participants in the context of scheduled ASD clinical visits required significant effort. However, once recruited, participants completed most study activities, regardless of behavioral symptom severity. Research activities did not adversely affect the clinical visit.


Compliance to technical guidelines for radiotherapy treatment in relation to patient safety.
To determine the compliance of radiation technologists to technical guidelines in daily practice for radiotherapy treatment and whether there are differences in compliance across organizational units. On the basis of consensus, radiation technologists constructed a flowchart describing the work procedure of the irradiation of patients with breast cancer. Using video recordings, technologists in two units were observed to determine whether treatment was conducted in accordance with the flowchart. Data have been collected on one linear accelerator at the MAASTRO clinic, a radiotherapy clinic in the Netherlands. Fifty-six treatments for breast cancer were analyzed in two treatment units. Percentage compliance to the most important issues for patient safety. An overall compliance of 59% (range: 2-100%) was shown on the 18 most important tasks for patient safety. Between the two units, the compliance varied from 21% to 81%. Tasks considered important by independent assessment had higher levels of compliance. Video-taped observation proved to be an effective tool for determining compliance in daily practice. A large variation in practice within and across units was detected by the video observations suggesting a need for standard operating procedures to improve the safety of radiotherapy.


The value of diffusion-weighted MRI for prostate cancer detection and localization.
The aim of this study was to evaluate the role of prebiopsy T2-weighted imaging (T2WI), quantitative diffusion-weighted imaging (DWI), and the combination of these magnetic resonance (MR) techniques (T2WI+DWI) in the detection and localization of peripheral zone prostate cancer. T2WI and DWI (b value = 800 s/mm2) with an endorectal coil at 1.5 T were performed prospectively in 43 consecutive male patients with suspicion of prostate cancer before a systematic 12-core prostate biopsy. The peripheral zone of the prostate was evaluated after dividing it into sextants (n = 258). Minimum apparent diffusion coefficient (ADC) values of each sextant in the peripheral zone were measured. Two core biopsies were obtained from each sextant under transrectal ultrasound guidance. The mean minimum ADC values of the malignant sextants were significantly lower than that of noncancerous tissue, with a significant negative correlation between the ADC value and the Gleason score. The sensitivity, specificity, and area under the receiver operating characteristic curve for the detection and localization of prostate cancer within the peripheral zone were 71%, 77%, and 0.741 for T2WI alone; 84%, 82%, and 0.830 for quantitative DWI alone; and 81%, 92%, and 0.863 for T2WI+DWI, respectively. The use of quantitative DWI, alone or combined with T2WI, improved diagnostic performance in prostate cancer detection and localization compared with T2WI alone (P = 0.020 and P = 0.001, respectively). Prebiopsy DWI is valuable in detecting, localizing, and grading prostate cancer within the peripheral zone, and the lowest ADC values can indicate the regions to be biopsied.


Duodenopancreatic resections in patients with multiple endocrine neoplasia type 1.
To review the authors' 7-year experience with a surgical approach for pancreatic and duodenal neuroendocrine tumors (NETs) in patients with multiple endocrine neoplasia type 1 (MEN 1) designed to remove all gross tumor with limited complications, preserving pancreatic function. MEN 1 is an autosomal dominant familial neoplasia syndrome characterized by the development of NETs of the duodenum and pancreas. Some tumors are clinically insignificant or follow a benign course, although a subset pursues a malignant, lethal natural history; the risk of surgical management must be appropriate to the disease course. The clinical, biochemical, genetic, and pathologic data were retrospectively reviewed for 21 consecutive MEN 1 patients undergoing pancreatic resection for NETs between 1993 and 1999 at one institution. Age at operation, presenting symptoms, results of preoperative and intraoperative localization studies, major and minor complications, and pathology, including metastases, were analyzed. The surgical approach was selected based on the location and size of the tumors. Five patients required pancreaticoduodenectomy, 11 patients underwent non-Whipple pancreatic resections, and 5 underwent simple enucleation of benign NETs. The incidence of regional lymph node metastases was 33%. Major pancreatic procedures can be performed safely in most patients with MEN 1 and NETs. Because NETs are the most common MEN 1-related cause of death in the authors' kindreds, an aggressive surgical approach, including early intervention before malignant spread and major pancreatic resection where indicated, appears justified.


Evaluation of oral terfenadine for treatment of the common cold.
This study was a single center trial comparing the effects of the nonsedating antihistamine terfenadine, at a dose of 120 mg twice a day, with placebo in the treatment of rhinitis symptoms associated with the common cold. Forty-nine subjects were treated with terfenadine, 120 mg twice each day, and 48 subjects were treated with placebo twice each day for four or five days. Evaluations by both subjects and physicians suggest that terfenadine at 120 mg given twice daily marginally improved sneezing and total symptom scores at day 4. When comparing terfenadine to placebo, neither the symptoms nor signs of the common cold improved in a clinically or statistically significant manner. Terfenadine was well tolerated and had a low incidence of side effects. Terfenadine was found to be ineffective in the treatment of the signs and symptoms of the common cold.


N-silyl-tethered radical cyclizations: a new synthesis of gamma-amino alcohols.
[reaction: see text] Various allylic and propargylic amines bearing a protecting group (PG) have been employed in N-silyl-tethered radical cyclizations. The resulting silapyrrolidine adducts could be smoothly oxidized, creating access to gamma-amino alcohols. The silylation, radical cyclization, and oxidation reactions could be consolidated in a one-pot process.


Maintenance of Nef-mediated modulation of major histocompatibility complex class I and CD4 after sexual transmission of human immunodeficiency virus type 1.
Viruses encounter changing selective pressures during transmission between hosts, including host-specific immune responses and potentially varying functional demands on specific proteins. The human immunodeficiency virus type 1 Nef protein performs several functions potentially important for successful infection, including immune escape via down-regulation of class I major histocompatibility complex (MHC-I) and direct enhancement of viral infectivity and replication. Nef is also a major target of the host cytotoxic T-lymphocyte (CTL) response. To examine the impact of changing selective pressures on Nef functions following sexual transmission, we analyzed genetic and functional changes in nef clones from six transmission events. Phylogenetic analyses indicated that the diversity of nef was similar in both sources and acutely infected recipients, the patterns of selection across transmission were variable, and regions of Nef associated with distinct functions evolved similarly in sources and recipients. These results weighed against the selection of specific Nef functions by transmission or during acute infection. Measurement of Nef function provided no evidence that the down-regulation of either CD4 or MHC-I was optimized by transmission or during acute infection, although rare nef clones from sources that were impaired in these activities were not detected in recipients. Nef-specific CTL activity was detected as early as 3 weeks after infection and appeared to be an evolutionary force driving the diversification of nef. Despite the change in selective pressure between the source and recipient immune systems and concomitant genetic diversity, the majority of Nef proteins maintained robust abilities to down-regulate MHC-I and CD4. These data suggest that both functions are important for the successful establishment of infection in a new host.


Clustering of ipsilateral cortico-cortical projection neurons to area 7 in the rhesus monkey.
The distribution within individual cytoarchitectonic areas of the cells of origin of ipsilateral cortico-cortical fibres to area 7 of the parietal lobe of the monkey has been studied. After injections of horseradish peroxidase into area 7, labelled cells in a variety of cortical areas were plotted and their distribution along the length of the cortex analysed. Significant clustering of labelled cells was seen wherever their numbers were sufficient for meaningful statistical analysis. In most cases, further analysis using correlation techniques revealed a significant banding of labelled cells across the cortex. Typical bands varied from 500-800 microns in width, and formed an irregular branching and rejoining pattern across the cortex. The intra-area distribution of cortico-cortical projection neurons is comparable to the distribution of neurofibrillary tangles in the cortex in Alzheimer's disease.


[Key morphofunctional transformations in the evolution of chiropterans (Bats, Chiroptera)].
Study on the morphology and morphogenesis of wing membranes in Bats has revealed some peculiarities in their structure and development. Understanding the embryogenesis of these animals, as well as attraction of data obtained on their molecular genetics and paleontology, allows one to single out some factors that could have initiated evolutionary modifications in development programs. A scenario of the key morphofunctional transformations in the forelimbs during the evolution of chiropterans is given.


Patients' preferences for technical versus interpersonal quality when selecting a primary care physician.
To assess patients' use of and preferences for information about technical and interpersonal quality when using simulated, computerized health care report cards to select a primary care provider (PCP). Primary data collected from 304 adult consumers living in Los Angeles County in January and February 2003. We constructed computerized report cards for seven pairs of hypothetical individual PCPs (two internal validity check pairs included). Participants selected the physician that they preferred. A questionnaire collected demographic information and assessed participant attitudes towards different sources of report card information. The relationship between patient characteristics and number of times the participant selected the physician who excelled in technical quality are estimated using an ordered logit model. Ninety percent of the sample selected the dominant physician for both validity checks, indicating a level of attention to task comparable with prior studies. When presented with pairs of physicians who varied in technical and interpersonal quality, two-thirds of the sample (95 percent CI: 62, 72 percent) chose the physician who was higher in technical quality at least three out of five times (one-sample binomial test of proportion). Age, gender, and ethnicity were not significant predictors of choosing the physician who was higher in technical quality. These participants showed a strong preference for physicians of high technical quality when forced to make tradeoffs, but a substantial proportion of the sample preferred physicians of high interpersonal quality. Individual physician report cards should contain ample information in both domains to be most useful to patients.


Melatonin rescues the mice brain against cisplatin-induced neurodegeneration, an insight into antioxidant and anti-inflammatory effects.
Herein, we evaluated the neuroprotective effect of melatonin against cisplatin-induced oxidative damage, neuroinflammation, and synaptic dysfunction in mice. Cisplatin was administered at a dose of 2 mg/kg for eleven consecutive days to induce symptoms of cognitive impairment and neurodegeneration, while melatonin was administered at a 20 mg/kg dose for thirty consecutive days. We used various experimental techniques such as western blotting, immunofluorescence analysis, and oxidative stress marker assays to support our notion. Moreover, for cognitive impairment, we conducted behavioral analyses such as Morris Water Maze (MWM) and Y-Maze tests. The results indicated that melatonin attenuated oxidative stress by upregulating the expression of NF-E2-related factor-2 (Nrf2) dependent anti-oxidative protein levels. Similarly, melatonin positively modulated the expression of Sirt1 (a member of the sirtuin family), Phospho-AMPKα (Thr172), peroxisome proliferator-activated receptor (PPARγ), PPAR gamma coactivator 1 alpha (PGC-1α) coupled to downregulation of neuroinflammatory mediators and markers such as nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). Moreover, melatonin significantly upregulated the expression of synaptic markers such as postsynaptic density protein -95 (PSD-95), synaptosomal-associated protein 23 (SNAP-23), and synaptophysin compared to the cisplatin alone group. Furthermore, the results of behavior tests suggested that melatonin significantly improved the cognitive functions of the cisplatin injected mice.


Scaling Up Parenting Interventions is Critical for Attaining the Sustainable Development Goals.
Of all the potentially modifiable influences affecting children's development and mental health across the life course, none is more important than the quality of parenting and family life. In this position paper, we argue that parenting is fundamentally linked to the development of life skills that children need in order to achieve the United Nations Sustainable Development Goals. We discuss key principles that should inform the development of a global research and implementation agenda related to scaling up evidence-based parenting support programs. Research over the past 50 years has shown that parenting support programs of varied intensity and delivery modality can improve a wide range of developmental, emotional, behavioral and health outcomes for parents and their children. Such findings have been replicated across culturally and socioeconomically diverse samples, albeit primarily in studies from Western countries. We highlight the evidence for the relevance of parenting interventions for attaining the SDGs globally, and identify the barriers to and strategies for achieving their scale-up. The implications of the global COVID-19 pandemic for the delivery of evidence-based parenting support are also discussed.


Factors associated with multi-drug-resistant tuberculosis in Dakar, Senegal, 2010-2016.
According to the World Health Organization, multidrug-resistant tuberculosis (MDR-TB) represents a major obstacle towards successful TB treatment and control. In Dakar, MDR-TB management began in 2010 with the strengthening of diagnostic resources. The objective of this study was to identify the factors associated with multidrug-resistant tuberculosis in Dakar between 2010 and 2016. We conducted a case-control study from January 10 to February 28, 2017 in tuberculosis centers in Dakar. of 169 cases and 507 controls. We used logistic regression with Epi-info version 7.2.1. to estimate the odds ratios of association. Factors significantly associated with MDR-TB were: residing in a periurban area (ORa=1.8; 95% CI (1.5-4.9); p=0.024), presence of MDR-TB in the entourage of patient (ORa=7.0; 95% CI (6.1-9.5); p=0.002), previous treatment failure (ORa=29.5; 95% CI (27.3-30.1); p=0.000), treatment not directly observed by a health care provider (ORa=4.3; 95% CI (4.1-7,2); p=0.000) and irregularity of treatment (ORa=1.7; 95% CI (0.5-5.4); p=0.037). Focusing interventions on population at-risk will prevent MDR-TB.


Understanding self care coping styles in patients with chronic heart failure: A systematic review.
Physical and psychological self care coping styles affect the quality of life among patients with heart failure. Understanding coping styles and related factors is important. 1) To understand coping involved with self care of physical and psychological aspects in chronic heart failure patients and 2) to understand the associated factors with self care coping. A systemic review of databases PubMed, CINHAL, PsycINFO and Airti Library were searched with key terms: 'heart failure', 'coping' and 'self-care' for the period of January 1984 to October 2013. Twenty-six studies were included. Emotion-focused coping (acceptance and disavowal) and problem-focused coping are positively associated with better physical and psychological self care, whereas an emotional approach with escape avoidance was negatively related to adaptive self care. Enhancing the use of emotion-focused coping with acceptance could facilitate problem-focused coping regarding physical self care (medication and dietary adherence) and reduce adverse drug effects. The associated factors in coping styles of physical and psychological self care included socio-demographic factors, health condition-related factors, patient-related factors and spirituality and religion factors. Emotion-focused coping with acceptance and disavowal, as well as problem-focused coping, may positively influence physical and psychological self care. Health care professionals should accept and allow patients to use emotion-focused coping, then help patients to use problem-focused coping skills. The influencing factors have important roles in individuals' coping styles. There is a lack of experimental and qualitative research to determine how the influencing factors affect self care coping, since this review is primarily of revealed correlational studies.


A Systematic Review of Parenting Scales Measurement Invariance/ Equivalence of by Race and Ethnicity: Recommendations for Inclusive Parenting Research.
The limited inclusion of racial/ethnic minorities in the development and validation of parenting measures limits our understanding of whether parenting constructs are valid in racial and ethnic minorities. Tests of measurement invariance/equivalence (MI/E) of parenting measures can help evaluate the validity of parenting constructs among racial/ethnic minorities. This systematic review summarized studies on MI/E of parenting constructs by race/ethnicity and evaluated the strength of the evidence. A literature search was conducted using various databases and references to retrieve studies from the United States. Indeed, 10 studies were identified that tested for MI/E of eight parenting scales by race/ethnicity. Only one scale showed moderate evidence of MI/E, five showed weak evidence of MI/E, and two showed no evidence of MI/E. Most studies (80%) used factor analytic methods to test for MI/E, but only two studies (20%) examined all levels of invariance. These findings show that differences exist in how racial/ethnic minorities perceive parenting constructs. Further research is needed to develop more inclusive parenting measures, to protect against the ways in which biased measures may pathologize or misrepresent parenting practices among racial/ethnic minorities.


Comparison of the effects of RNase-negative and wild-type classical swine fever virus on peripheral blood cells of infected pigs.
Elimination of the RNase activity of classical swine fever virus (CSFV) glycoprotein E(rns) was previously shown to result in virus attenuation. Specific reduction of B cell numbers in the peripheral blood, a typical symptom of CSFV infection in pigs, was not detected on infection with the RNase-negative mutant C-H346Delta [Meyers et al. (1999). J Virol 73, 10224-10235]. The present report shows that this feature is restricted to this specific virus mutant, and does not represent a general property of RNase-negative CSFV. The effects induced by infection with two other RNase-negative and wild-type (wt) CSFV strains on the composition of peripheral blood cells have been further analysed. For all viruses, not only general leukopenia but also a reduction of different subsets of leukocytes (T-lymphocytes, monocytes and granulocytes) was detected. Similar to the results with B-cells, no significant differences with regard to changes in cell number were determined for RNase-negative mutants and wt virus during the initial phase of infection. Later, the values returned to pre-infection levels for the mutants, but stayed at low levels in the wt virus-infected animals. A major difference was reflected in the virus load of the infected animals, which was dramatically higher for pigs infected with wt CSFV, so that reduction of the virus load represents a further marker for attenuation resulting from RNase destruction. Attenuation was also detectable for the RNase-negative mutant C-W300G, which showed rapid reversion to the wt sequence within the infected pig. The prevention of fatal disease after infection with C-W300G is apparently determined during the short time between infection and reversion, as the virus revertant reisolated from infected pigs was shown to be virulent when used for infection in a follow-up study. Reversion of C-W300G was also detected in tissue culture during passage on swine testis epithelioid cells and porcine transformed kidney (MAX) cells, whereas the mutation was stable when SK6 or 38A1D cells were tested.


Small proteins modulate ion-channel-like ACD6 to regulate immunity in Arabidopsis thaliana.
The multi-pass transmembrane protein ACCELERATED CELL DEATH 6 (ACD6) is an immune regulator in Arabidopsis thaliana with an unclear biochemical mode of action. We have identified two loci, MODULATOR OF HYPERACTIVE ACD6 1 (MHA1) and its paralog MHA1-LIKE (MHA1L), that code for ∼7 kDa proteins, which differentially interact with specific ACD6 variants. MHA1L enhances the accumulation of an ACD6 complex, thereby increasing the activity of the ACD6 standard allele for regulating plant growth and defenses. The intracellular ankyrin repeats of ACD6 are structurally similar to those found in mammalian ion channels. Several lines of evidence link increased ACD6 activity to enhanced calcium influx, with MHA1L as a direct regulator of ACD6, indicating that peptide-regulated ion channels are not restricted to animals.


The incubation periods of Dengue viruses.
Dengue viruses are major contributors to illness and death globally. Here we analyze the extrinsic and intrinsic incubation periods (EIP and IIP), in the mosquito and human, respectively. We identified 146 EIP observations from 8 studies and 204 IIP observations from 35 studies. These data were fitted with censored Bayesian time-to-event models. The best-fitting temperature-dependent EIP model estimated that 95% of EIPs are between 5 and 33 days at 25°C, and 2 and 15 days at 30°C, with means of 15 and 6.5 days, respectively. The mean IIP estimate was 5.9 days, with 95% expected between days 3 and 10. Differences between serotypes were not identified for either incubation period. These incubation period models should be useful in clinical diagnosis, outbreak investigation, prevention and control efforts, and mathematical modeling of dengue virus transmission.


The place of information and communication technology-mediated consultations in primary care: GPs' perspectives.
New information and communication technologies such as email and text messaging have been shown to be useful in some aspects of primary care service delivery. Little is known about Scottish GPs' attitudes towards the adoption of these technologies as routine consultation tools. To explore GPs' perceptions of the potential place of new non-face-to-face consultation technologies in the routine delivery of primary care; to explore GPs' perceived barriers to the introduction of these technologies and to identify the processes by which GPs feel that new consultation technologies could be incorporated into routine primary care. Qualitative interview study: 20 in-depth semi-structured interviews carried out with maximum variation sample of GPs across Scotland. Whilst the face-to-face consultation was seen as central to much of the clinical and diagnostic work of primary care, many GPs were conditionally willing to consider using new technologies in the future, particularly to carry out administrative or less complex tasks and therefore maximize practice efficiency and patient convenience. Key considerations were access to appropriate training, IT support and medico-legal guidance. GPs are conditionally willing to use new consultation media if clinically appropriate and if medico-legal and technical support is available.


Generation and characterization of DNA vaccines targeting the nucleocapsid protein of severe acute respiratory syndrome coronavirus.
Severe acute respiratory syndrome (SARS) is a serious threat to public health and the economy on a global scale. The SARS coronavirus (SARS-CoV) has been identified as the etiological agent for SARS. Thus, vaccination against SARS-CoV may represent an effective approach to controlling SARS. DNA vaccines are an attractive approach for SARS vaccine development, as they offer many advantages over conventional vaccines, including stability, simplicity, and safety. Our investigators have previously shown that DNA vaccination with antigen linked to calreticulin (CRT) dramatically enhances major histocompatibility complex class I presentation of linked antigen to CD8(+) T cells. In this study, we have employed this CRT-based enhancement strategy to create effective DNA vaccines using SARS-CoV nucleocapsid (N) protein as a target antigen. Vaccination with naked CRT/N DNA generated the most potent N-specific humoral and T-cell-mediated immune responses in vaccinated C57BL/6 mice among all of the DNA constructs tested. Furthermore, mice vaccinated with CRT/N DNA were capable of significantly reducing the titer of challenging vaccinia virus expressing the N protein of the SARS virus. These results show that a DNA vaccine encoding CRT linked to a SARS-CoV antigen is capable of generating strong N-specific humoral and cellular immunity and may potentially be useful for control of infection with SARS-CoV.


Proteomics to Identify New Blood Biomarkers for Diagnosing Patients With Acute Stroke.
Background Blood biomarkers are a potential tool for early stroke diagnosis. We aimed to perform a pilot and exploratory study on untargeted blood biomarkers in patients with suspected stroke by using mass spectrometry analysis. Methods and Results This was a prospective observational study of consecutive patients with suspected stroke admitted within 6 hours of last being seen well. Blood samples were collected at admission. Patients were divided into 3 groups: ischemic stroke (IS), intracerebral hemorrhage (ICH), and stroke mimics. Quantitative analysis from mass spectrometry data was performed using a supervised approach. Biomarker-based prediction models were developed to differentiate IS from ICH and ICH+stroke mimics. Models were built aiming to minimize misidentification of patients with ICH as having IS. We included 90 patients, one-third within each subgroup. The median age was 71 years (interquartile range, 57-81 years), and 49 participants (54.4%) were women. In quantitative analysis, C3 (complement component 3), ICAM-2 (intercellular adhesion molecule 2), PLGLA (plasminogen like A), STXBP5 (syntaxin-binding protein 5), and IGHV3-64 (immunoglobulin heavy variable 3-64) were the 5 most significantly dysregulated proteins for both comparisons. Biomarker-based models showed 88% sensitivity and 89% negative predictive value for differentiating IS from ICH, and 75% sensitivity and 95% negative predictive value for differentiating IS from ICH+stroke mimics. ICAM-2, STXBP5, PLGLA, C3, and IGHV3-64 displayed the highest importance score in our models, being the most informative for identifying patients with stroke. Conclusions In this proof-of-concept and exploratory study, our biomarker-based prediction models, including ICAM-2, STXBP5, PLGLA, C3, and IGHV3-64, showed 75% to 88% sensitivity for identifying patients with IS, while aiming to minimize misclassification of ICH. Although our methodology provided an internal validation, these results still need validation in other cohorts and with different measurement techniques.


[Reconstructive surgery in laryngostenosis in children].
Methods of laryngoplasty with usage of costal cartilage autotransplant and segmental laryngeal resection were applied in 33 patients with laryngostenosis of various etiology. Decannulation of the patients during the first 4 months after beginning of the treatment was made in 75% patients with one-stage laryngoplasty. A new method of stenting in reconstructive operations on the larynx is proposed. The endolumen technique of silicon stent fixation isolated from tracheostome cannula is thought an optimal method of stenting. Surgery is optimal early after verification of the diagnosis. Early operations make it possible to optimize prognosis of one-stage treatment as they reduce the number of complications after long-term carrying of tracheostomic cannula as well as provide better socio-psychological adaptation of the patients.


Functional assays for classification of BRCA2 variants of uncertain significance.
The assessment of the influence of many rare BRCA2 missense mutations on cancer risk has proved difficult. A multifactorial likelihood model that predicts the odds of cancer causality for missense variants is effective, but is limited by the availability of family data. As an alternative, we developed functional assays that measure the influence of missense mutations on the ability of BRCA2 to repair DNA damage by homologous recombination and to control centriole amplification. We evaluated 22 missense mutations from the BRCA2 DNA binding domain (DBD) that were identified in multiple breast cancer families using these assays and compared the results with those from the likelihood model. Thirteen variants inactivated BRCA2 function in at least one assay; two others truncated BRCA2 by aberrant splicing; and seven had no effect on BRCA2 function. Of 10 variants with odds in favor of causality in the likelihood model of 50:1 or more and a posterior probability of pathogenicity of 0.99, eight inactivated BRCA2 function and the other two caused splicing defects. Four variants and four controls displaying odds in favor of neutrality of 50:1 and posterior probabilities of pathogenicity of at least 1 x 10(-3) had no effect on function in either assay. The strong correlation between the functional assays and likelihood model data suggests that these functional assays are an excellent method for identifying inactivating missense mutations in the BRCA2 DBD and that the assays may be a useful addition to models that predict the likelihood of cancer in carriers of missense mutations.


Management of acute otitis media after publication of the 2004 AAP and AAFP clinical practice guideline.
Observation without initial antibiotic therapy was accepted as an option for acute otitis media (AOM) management in the 2004 American Academy of Pediatrics and American Academy of Family Physicians clinical practice guideline. The guideline also recommended amoxicillin as the first-line treatment for most children, and analgesic treatment to reduce pain if it was present. Our objective was to compare the management of AOM after publication of the 2004 guideline. We analyzed the National Ambulatory Medical Care Survey, 2002-2006 (N = 1114), which occurred in US physicians' offices. The patients were children aged 6 months to 12 years who were diagnosed with AOM. The time comparisons were the 30-month periods before and after the guideline. The main outcome was the encounter rate at which no antibiotic-prescribing was reported. Secondary outcomes were the identification of factors associated with encounters at which no antibiotic-prescribing was reported and antibiotic- and analgesic-prescribing rates. The rate of AOM encounters at which no antibiotic-prescribing was reported did not change after guideline publication (11%-16%; P = .103). Independent predictors of an encounter at which no antibiotic-prescribing was reported were the absence of ear pain, absence of reported fever, and receipt of an analgesic prescription. After guideline publication, the rate of amoxicillin-prescribing increased (40%-49%; P = .039), the rate of amoxicillin/clavulanate-prescribing decreased (23%-16%; P = .043), the rate of cefdinir-prescribing increased (7%-14%; P = .004), and the rate of analgesic-prescribing increased (14%-24%; P = .038). Although management of AOM without antibiotics has not increased after the publication of the 2004 American Academy of Pediatrics and American Academy of Family Physicians clinical practice guideline, children who did not receive antibiotics were more likely to have mild infections. In accordance with the guideline, the prescribing of amoxicillin and analgesics has increased. Contrary to the guideline, the prescribing of amoxicillin/clavulanate has decreased, whereas the prescribing of cefdinir has increased.


[Variants in the growth of meningiomas of the base of the skull spreading into the orbit and paranasal sinuses].
Meningiomas of the skull base involving the orbit and paranasal sinuses were diagnosed in 254 patients. The patients were operated on in 1982-1991. All craniocephalic meningiomas involve the anterior skull base bones. The involvement presents either as destruction (nodular tumor) or as hyperostosis (infiltrative growth of the tumor). All patients were divided into 8 groups with different location of skull bones involvement. A classification of meningiomas of skull base disseminating into the orbit and paranasal sinuses is proposed, proceeding from the anatomical principle. This classification helps plan a surgical access, scope of intervention, probable size of skull defect and method of its closure, possible postoperative functional and cosmetic defects.


FRACTURES OF FACIAL BONES.
A detailed review was made of 1025 consecutive patients with "face-bone" fractures admitted to four Montreal hospitals over the five-year period 1958-1962, inclusive. In addition a survey was carried out of the other general hospitals in Greater Montreal in order to obtain admission figures for facial-bone fractures and for total hospital cases. In the study group the common causes of face-bone fractures were found to be fights, traffic accidents, falls, and athletic pursuits. Very few of these injuries occurred in industrial settings. A distinctly vulnerable group is made up of males between ages 16 and 35 years. In order of frequency of occurrence these injuries involve the nose, lower jaw, cheekbone, upper jaw, and zygomatic arch. The experience throughout metropolitan Montreal indicated that more persons with face-bone fractures require hospital treatment each year, but the increase is approximately parallel to the upward trend of total hospital admissions.


Adolescents With Cancer Need Trustworthy Information and Prefer to Receive It From a Human Source Rather Than From the Internet: A Qualitative Study.
Background: In pediatric cancer, the legal obligation to provide information is usually toward the parents who are the authorized signatories of the informed consent form. It is now known that aside from providing information to the parents, it is also very important to provide information to the children and adolescents themselves. The question is how the adolescents relate to this. What information do they already possess and what would they like to know? Would they wish to hear the truth in all situations and at what stage? What are their preferred sources of information? Method: A qualitative study that included in-depth interviews with 19 adolescents with cancer, aged 8.5-18, who were receiving active treatments and had been diagnosed at least 1 month previously. The interviews were guided by 15 open-ended questions. Findings: The analysis of the interviews indicated that adolescents know quite a lot about the course of their disease and the information they lack is mainly etiological. The participants reported a lack of knowledge concerning sexuality and a sense of discomfort talking about it, leaving them with open questions. They all claimed that it is important to tell the truth: "Even if the truth is difficult, it is important to tell it." The participants reported that information can be scary, so it must be structured and adapted to the age and emotional readiness of the individual. Most of the participants prefer not to use the internet as an information resource due to the profusion of stressful and non-adapted information. Conclusion: Adolescents with cancer need trustworthy information and prefer to receive it from a human source rather than from the internet. Not telling the truth can lead them to feel fear and loneliness. The medical staff must operate in sensitive and creative ways to provide adolescents with access to information on various subjects, including sexuality, which they are ashamed to talk about, leaving them with a sense of shame and a lack of knowledge in this area.


Myristica Fragrans Houtt Extract Attenuates Neuronal Loss and Glial Activation in Pentylenetetrazol-Induced Kindling Model.
Inflammatory reactions are closely associated with the development and progression of epilepsy. It has been shown that inhibition of pro-inflammatory cytokines, which are released from activated astrocytes and microglia, are considered to be an effective therapeutic approach for the treatment of epileptic disorders. Regarding the anti-inflammatory effects of nutmeg (Myristica fragrans Houtt), the present study was designed to investigate whether the nutmeg ethanolic extract could exert anticonvulsant and inhibitory effects on glial activation in pentylenetetrazol (PTZ)-induced mice model of kindling. Ethanolic extract of nutmeg was administrated intraperitoneally (i.p.) 1 hour before PTZ injection or one week before PTZ as a separate group, to become fully-kindled. The chemical components of nutmeg extract were analyzed by gas chromatography mass spectrometry (GC-MS). Immunostaining against neuronal and glial markers was performed on hippocampus sections. GC-MS data indicated that the main components of nutmeg extract are myristic acid (39.93%), elemicin (22.16%) and myristicin (11.17%). Behavioral studies showed that pre-treatment of nutmeg extract effectively reduced seizures behavior, decreased cell death, and ameliorated glial activation that is followed by PTZ administration. In conclusion, nutmeg extract might be regarded as a useful supplementary agent in epilepsy treatment through its attenuation of neuronal loss and glial activation.


Parent-child bonding and attachment during pregnancy and early childhood following congenital heart disease diagnosis.
Diagnosis and treatment of congenital heart disease (CHD) can present challenges to the developing parent-child relationship due to periods of infant hospitalization and intensive medical care, parent-infant separations, child neurodevelopmental delay and feeding problems, and significant parent and child distress and trauma. Yet, the ways in which CHD may affect the parent-child relationship are not well-understood. We systematically reviewed the evidence on parental bonding, parent-child interaction, and child attachment following CHD diagnosis, according to a pre-registered protocol (CRD42019135687). Six electronic databases were searched for English-language studies comparing a cardiac sample (i.e., expectant parents or parents and their child aged 0-5 years with CHD) with a healthy comparison group on relational outcomes. Of 22 unique studies, most used parent-report measures (73%) and yielded mixed results for parental bonding and parent-child interaction quality. Observational results also varied, although most studies (4 of 6) found difficulties in parent-child interaction on one or more affective or behavioural domains (e.g., lower maternal sensitivity, lower infant responsiveness). Research on parental-fetal bonding, father-child relationships, and child attachment behaviour was lacking. Stronger evidence is needed to determine the nature, prevalence, and predictors of relational disruptions following CHD diagnosis, and to inform targeted screening, prevention, and early intervention programs for at-risk dyads.