Building Communication and Conflict Management Awareness in Surgical Education.
A group of surgeons and a medical educator constructed a curriculum to strengthen communication and emotional intelligence skills in the surgical setting. The curriculum consisted of a small group discussion series occurring during medical students' eight-week surgery clerkship. The curriculum targeted the following objectives: building team rapport, exploring self-management strategies in team communication, recognizing communication styles, diagnosing conflict, identifying opportunities in professional and personal development, and discussing professionalism in medicine. Students completed pre-post Likert style tests about their knowledge and understanding of the above-mentioned topics. Texas A&M University College of Medicine, Surgical Clerkship at Baylor Scott and White Medical Center, a level 1 trauma center, in Temple, TX. Twenty-four students in their third year of medical school completed the communication curriculum. Wilcoxon sign test was used to analyze the non-parametric data and multiple repeat tests required the significance level (p-Value) be adjusted to 0.003. Students showed significant increase in understanding of conflict management, their ability to communicate effectively, and their awareness of communication preferences (p < 0.001). In addition, they recognized better ways to engage with other students, residents, and staff on their rotation (p = 0.002) and felt more confident in their ability to handle feedback (p = 0.001). Open-ended responses on the post-test had overwhelmingly positive feedback with themes of awareness, psychological safety, and team rapport. Finally, students requested that the curriculum be taught longitudinally throughout their third-year clerkships. Our curriculum enabled students to improve their awareness of communication, conflict management, team dynamics, and professionalism. These important competencies will support students throughout their training and in their practice as future surgeons.


Conductance and dye permeability of a rectifying electrical synapse.
Electrical synapses provide a basis for efficient signal transmission in a wide variety of nervous systems. These synapses are composed of specialized cell-to-cell contacts known as nexuses or gap junctions which mediate the direct transfer of ions and small molecules between adjacent cell interiors by way of intercellular channels embedded in the junctional membrane. The crayfish giant motor synapse (GMS) was the first cell-to-cell junction clearly demonstrated to operate by an electrical mechanism. Current applied to the presynaptic lateral giant (LG) axon or to the neurite of the postsynaptic giant flexor motoneurone (MoG) spreads passively through the synapse into the adjacent neurone. Each GMS behaves like an electrical rectifier: its conductance is high when LG is positive with respect to MoG, and decreases dramatically when the sign of the trans-synaptic voltage is reversed. We have now examined GMS conductance and dye permeability at thoracic and abdominal levels of the crayfish nerve cord. At both levels, values of GMS chord conductance fit a simple Boltzmann model in which the conductance of individual synaptic channels is assumed to be voltage dependent. Moreover, thoracic synapses display higher limiting conductances than do those at an abdominal level, apparently as a result of their larger size. We also find that synapses at both locations are permeable to the fluorescent dye Lucifer yellow, even in conditions where electrical conductance is low. These results provide a framework for understanding the operation and functional limits of rectifying electrical synapses, and illustrate that dye permeability can be associated even with their relatively low conductance condition.


A model for widening access into medicine and dentistry: the SAMDA-BL project.
To assess whether assistance with and/or advice on the UK Universities & Colleges Admissions Service (UCAS) application process by undergraduate medical and dental students increases the offer rate to applicants from educational institutions situated in areas of socio-economic deprivation for medical and dental courses. A sample of 42 students making 172 applications in 2001 and another sample of 40 students making 158 applications in 2002 from 4 further education and sixth form colleges across East London were entered into the study. Applicants were either offered advice and assistance with writing their personal statement and extra curricular activities, such as work experience (group A) or advice only on the importance of the personal statement and extra curricular activities (group B). Applicants were also assisted with or advised to submit their applications early. All applicants were offered mock interviews. Main outcome measures The number of offers made to applicants by medical and dental schools and the dates of offered interviews. The total offer rate rose from 9% (preceding 4 years) to 38% (CI 25-51%, P < 0.05) in 2001 and 44% (CI 27-61%, P < 0.05) in 2002, confirming a rising trend in offers to applicants in group A. Applicants who were only advised on the importance of the personal statement and extra curricular activities (group B) showed smaller increases, ranging from 10% to 29% for 2001 and from 28% to 37% for 2002. The dates for the offered interviews were earlier in group A than group B. Undergraduate students can help applicants to medical and dental schools from socio-economically deprived areas submit earlier, improved UCAS applications and provide interview practice, all of which are associated with a higher offer rate. Applicants benefit from advice on activities such as work experience, community work and personal interests, but assistance in organising such activities increases the offer rate more. The study was conducted during a period of time when there was an increase in the number of medical school places available. Therefore, more research is needed to confirm that such assistance can increase applicants' offer rates elsewhere, particularly applications from students who traditionally would not apply for medicine or dentistry.


Long-Distance Counter Calling in Maned Wolves: Friends or Foes?
Maned wolves (Chrysocyon brachyurus) are monogamous and display biparental care for their young, although adults rarely spend time in close proximity. To better understand vocal interactions of maned wolves over long-distances, we passively recorded >10 months of audio data in the species' natural habitat and analyzed manual recordings of captive animals, covering the reproductive and non-reproductive seasons. In the natural habitat recordings, we found that maned wolves engage in vocal exchanges (termed interactive sequences) more often during the mating season, suggesting the existence of a partner attraction/reunion/guarding function, and also during the initial parental care period, suggesting communication among caregivers. We analyzed 21 interactive sequences, which were the only instances in which we could distinguish individuals, and found that the individuals interacting differed significantly in their roar-bark parameters, including duration, which also differed between males and females in captivity (male vocalizations were, on average, 0.124 s longer). We also found that interactive sequences in captive animals, involving two or more participants, almost always involved both sexes. These results suggest that acoustic interacting maned wolves are most likely male−female dyads.


The role of radiography in diagnosing, monitoring and prognosing juvenile idiopathic arthritis.
The current role of conventional radiography in the diagnosis, monitoring and prognosis of juvenile idiopathic arthritis (JIA) is reviewed, as its role has changed with the increasing use of ultrasound and magnetic resonance imaging, as well as with the introduction of biological drugs. Conventional radiography does not play an important role in the diagnosis of JIA, as this is based on history, clinical examination and laboratory findings. The main role of conventional radiography is in the detection and monitoring of growth disorders and chronic structural and morphological changes of the affected joints and bones, in addition to helping with the differential diagnosis of conditions that mimic JIA. Radiographic changes of the joints depend on the age of the child, the type and duration of arthritis and the specific joints affected. There are no standard protocols for arthritis monitoring and most indications for imaging are based on individual case-by-case decisions. The development of degenerative joint changes is considered a poor predictive factor, but there are no clear studies that more precisely define the predictive value of radiographic changes. Conventional radiography remains an important imaging modality in narrowing the differential diagnosis and in evaluating growth disorders and the developing destructive joint changes.


Functional properties of the spike glycoprotein of the emerging SARS-CoV-2 variant B.1.1.529.
The recently emerged B.1.1.529 (Omicron) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant has a highly divergent spike (S) glycoprotein. We compared the functional properties of B.1.1.529 BA.1 S with those of previous globally prevalent SARS-CoV-2 variants, D614G and B.1.617.2. Relative to these variants, B.1.1.529 S exhibits decreases in processing, syncytium formation, virion incorporation, and ability to mediate infection of cells with high TMPRSS2 expression. B.1.1.529 and B.1.617.2 S glycoproteins bind ACE2 with higher affinity than D614G S. The unliganded B.1.1.529 S trimer is less stable at low temperatures than the other SARS-CoV-2 Ss, a property related to its more "open" S conformation. Upon ACE2 binding, the B.1.1.529 S trimer sheds S1 at 37°C, but not at 0°C. B.1.1.529 pseudoviruses are relatively resistant to neutralization by sera from patients with coronavirus disease 2019 (COVID-19) and vaccinees. These properties of the B.1.1.529 S glycoprotein likely influence the transmission, cytopathic effects, and immune evasion of this emerging variant.


Climatic influence on conjunctival bacteria of patients undergoing cataract surgery.
To describe the monthly prevalence of conjunctival bacteria in patients undergoing cataract extraction and the possible climatic influence on it, in Madrid, in order to clarify postsurgical endophthalmitis pathogenesis. The lower conjunctival content sample of 4432 consecutive patients awaiting cataract surgery was cultured from January 1994 to December 1996. The dates of the operations and the rehospitalization for postsurgical endophthalmitis, if this took place, were checked. The isolated bacteria were grouped to study the statistical significance of the differences in the monthly prevalence differences (chi2 tests). Temperature and relative humidity are given monthly for the area where our patients live. The total frequency of the conjunctival bacteria increases in April, May, and June, when the daily average temperature rises from 12 to 22 degrees C and the relative humidity oscillates between 45 and 60% in our area. Bacteria groups' frequency was significantly higher as follows: Staphylococci coagulase negative ( > 60%) in April, May, and June; Corynebacterium sp ( > 33%), Staphylococcus Aureus ( > 8%), and other Gram-positive bacteria ( > 2.5%) in May; Streptococcus Pneumoniae increases ( > 3.4%) in March, November, and December; Haemophilus sp ( > 3.4%) in January and April; Gram-negative Cocci ( > 3%) in April; and other Streptococcus sp ( > 6%) in April, May, and September. Our incidence of rehospitalization for endophthalmitis after cataract extraction in May and June together was 3.37 times higher than in the other months. Conjunctival bacteria of our patients undergoing cataract surgery present a seasonal prevalence pattern, which could be considered as a predisposing condition for having postsurgical endophthalmitis in certain months.


Superoxide determines nitric oxide uptake rate by vascular smooth muscle cells.
Nitric oxide (NO) is generated in endothelial cells, which diffuses to vascular smooth muscle cells (SMCs), activates soluble guanylyl cyclase, and leads to blood vessel dilation. However, this scenario does not explain how SMCs are capable of competing with erythrocytic hemoglobin for NO in vivo. Here, we have developed a competition experiment to determine the NO uptake rate by SMCs and demonstrated that the SMC-NO uptake rate is positively dependent on intracellular superoxide levels. In addition, the superoxide-elicited NO influx is able to enhance cGMP production in SMCs. Our findings imply that vascular SMCs, in vivo, may use superoxide to compete with erythrocytic hemoglobin for NO and obtain the NO bioactivity.


Motivation to consume palatable foods as a predictor of body image dissatisfaction: Using the Power of Food Scale in a Brazilian sample.
The Power of Food Scale (PFS) is a questionnaire for self-assessing the motivation to consume palatable foods, especially in environments where food is abundant and constantly available. This study aimed to a) assess the factorial structure of the PFS in a Brazilian sample and b) examine the relationship between the power of food and body image dissatisfaction and BMI. The PFS and Body Shape Questionnaire (BSQ) were applied to a sample of 300 adults. Data were analysed using confirmatory factor analysis. Composite reliability (CR) was used to verify factor reliability. A partial least squares structural equation model was used to verify the effect of the PFS score on body image dissatisfaction. The PFS had an adequate factorial structure in this Brazilian sample, showing three well-defined factors: food available (CR = 0.91), food tasted (CR = 0.84), and food present (CR = 0.87). The BSQ showed one reliable factor (CR = 0.97). The power of the food aggregate factor significantly predicted body mass index (β = 0.16; p = .01) and body image dissatisfaction (β = 0.46; p < .001). The effect size was small for body mass index (f2 = 0.02) and medium for body image dissatisfaction (f2 = 0.26). The food present factor also had a slightly higher average among the three PFS factors. Women had higher PFS scores than men. Understanding the role that this motivation plays in physical and psychological outcomes such as body dissatisfaction can contribute to developing treatment strategies and support health professionals' performance in clinical settings.


Practice parameter for the assessment and treatment of children and adolescents with schizophrenia.
This Practice Parameter reviews the literature on the assessment and treatment of children and adolescents with schizophrenia. Early-onset schizophrenia is diagnosed using the same criteria as in adults and appears to be continuous with the adult form of the disorder. Clinical standards suggest that effective treatment includes antipsychotic medications combined with psychoeducational, psychotherapeutic, and educational interventions. Since this Practice Parameter was last published in 2001, several controlled trials of atypical antipsychotic agents for early-onset schizophrenia have been conducted. However, studies suggest that many youth with early-onset schizophrenia do not respond adequately to available agents and are vulnerable to adverse events, particularly metabolic side effects. Further research is needed to develop more effective and safer treatments.


Derepression of the USP22-FASN axis by p53 loss under oxidative stress drives lipogenesis and tumorigenesis.
Overproduction of reactive oxygen species (ROS) and aberrant lipid metabolism are established hallmarks of cancer; however, the role of ROS in lipid synthesis during tumorigenesis is almost unknown. Herein, we show that ROS regulates lipid synthesis and thus controls colorectal tumorigenesis through a p53-dependent mechanism. In p53 wild-type colorectal cancer (CRC) cells, hydrogen peroxide (H2O2)-induced p53 expression represses the transcription of deubiquitinase USP22, which otherwise deubiquitinates and stabilizes Fatty Acid Synthase (FASN), and thus inhibits fatty acid synthesis. Whereas, in p53-deficient CRC cells, ROS-mediated inhibition of USP22 is relieved, leading to FASN stabilization, which thus promotes lipid synthesis and tumor growth. In human CRC specimens, USP22 expression is positively correlated with FASN expression. Our study demonstrates that ROS critically regulates lipid synthesis and tumorigenesis through the USP22-FASN axis in a p53-dependent manner, and targeting the USP22-FASN axis may represent a potential strategy for the treatment of colorectal cancer.


Methods for the analysis of inositol phosphates.
Interest in the inositol phospholipids was stimulated by the simultaneous discoveries that the products of hydrolysis of these lipids could serve as messengers to activate to synergistic signaling pathways in hormonally responsive cells, namely, inositol 1,4,5-trisphosphate which causes the release of Ca2+ from intracellular stores and diacylglycerol which promotes the activation of protein kinase C. At the same time, Berridge and co-workers introduced relatively simple approaches to study the inositol phospholipid cycle. These included the use of [3H]inositol to label the inositol metabolites, all of which are confined to this cycle, and of Li+ to decrease the rate of degradation of the inositol phosphates. Water-soluble inositol phosphates and chloroform-soluble inositol phospholipids could then be separated by solvent partition and the inositol phosphates further separated by use of an anion-exchange resin. However, the subsequent application of high-performance liquid chromatography as a separation technique indicated the existence of many isomers of the inositol phosphates formed by different pathways of dephosphorylation and phosphorylation. Mapping of these metabolic pathways may be substantially complete, but novel pathways may still be discovered. We review both old and new methods of analysis of the inositol phosphates for the measurement of mass and radioactivity. Although the complexity of the cycle sometimes demands the use of sophisticated methods of separation and rigorous identification, older and inexpensive methods may still be useful for some purposes.


Spatiotemporal analysis of severe fever with thrombocytopenia syndrome in Shandong Province, China, 2014-2018.
Due to recent emergence, severe fever with thrombocytopenia syndrome (SFTS) is becoming one of the major public health problems in Shandong Province, China. The numbers of reported SFTS cases in general and the area with reported SFTS cases are both continuously increasing in recent years. However, spatiotemporal patterns and clusters of SFTS in Shandong Province have not been investigated yet. The surveillance data of SFTS in Shandong Province, China, during 2014-2018 were extracted from China Information System for Disease Control and Prevention (CISDCP). Geoda software was used to explore spatial autocorrelation analysis, and Satscan software was used to identify spatio-temporal clustering of cases. The results were presented in ArcMap. The annual average incidence was 0.567/100,000 in Shandong Province during 2014-2018. Results showed that the distribution of SFTS was not random but clustered in space and time. A most likely cluster including 15 counties was observed in the northeastern region of Shandong Province from January 1, 2015 to December 31, 2015 (Relative risk = 5.13, Log likelihood ratio = 361.266, P < 0.001). The number of SFTS cases in Shandong Province increased overall. Geographic information system analysis coupled with spatial analysis illustrated regions with SFTS clusters. Our results provide a sound evidence base for future prevention and control programs of SFTS such as allocation of the health resources, surveillance in high-risk regions, health education, improvement of diagnosis and so on.


Khat in the neighbourhood--local government responses to khat use in a London community.
There is increasing fear among the general public about khat, its use and users, and associated crime. In many English cities, neighborhoods with growing Somali populations and emerging khat-using scenes and markets have to find ways of managing the impact of the negative image of khat. This case study describes and analyzes how a local municipal authority can respond constructively by generating an evidence base, engaging in consultation, and endeavoring to identify the actual relationship between reported criminality and public nuisance and the alleged patterns of use and distribution of khat. It is argued that it is important to frame the khat in the community not as a "drug problem" but as a wider public health issue, for which appropriate solutions can be developed.


Peanut agglutinin, a marker for T-cell acute lymphoblastic leukemia with a good prognosis.
Peanut agglutinin (PNA) binding was studied in cells from 74 children with acute lymphoblastic leukemia (ALL). PNA positivity occurred in 50% of T-ALL (12 of 24) and was rare in other types of ALL. There was no clear relationship between PNA and initial white blood cell count, French-American-British classification, stage of differentiation of leukemic cells, hand mirror cells, and organomegaly at diagnosis. Prognosis, however, was significantly better (continuous complete remission, death) in the PNA-positive T-ALLs. It seems that PNA is a useful marker for a subgroup of T-ALL with a better prognosis.


UV RESISTANCE LOCUS8 mediates ultraviolet-B-induced stomatal closure in an ethylene-dependent manner.
Although the UV RESISTANCE LOCUS 8 (UVR8)-CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1)-ELONGATED HYPOCOTYL5 (HY5) signaling pathway, ethylene, hydrogen peroxide (H2O2), and nitric oxide (NO) all participate in ultraviolet-B (UV-B)-triggered stomatal closing, their interrelationship is not clear. Here, we found that UV-B-induced the expression of ethylene biosynthetic genes, production of ethylene, H2O2, and NO, and stomata closing were impaired in uvr8, cop1, and hy5 mutants. UV-B-induced NO production and stomata closing were also defective in mutants for ETHYLENE RESPONSE 1 (ETR1), ETHYLENE INSENSITIVE 2 (EIN2), and EIN3, but UV-B-triggered H2O2 generation was only inhibited in etr1. In either the absence or presence of UV-B, ethylene triggered H2O2 production but not NO generation and stomatal closure in cop1 and hy5, and stomata closing in cop1 and hy5 was induced by NO but not H2O2. Moreover, NO production and stomatal closure were constitutively caused by over-expression of COP1 or HY5 in ein2 and ein3, but not by over-expression of EIN2 or EIN3 in cop1 and hy5. Our data indicate that the UVR8-COP1-HY5 signaling module mediates UV-B-induced ethylene production, ethylene is then perceived by ETR1 to induce H2O2 synthesis. H2O2 induces NO generation and subsequent stomata closing via an EIN2, EIN3, COP1, and HY5-dependent pathway(s).


A nurse extern simulation experience through an innovative hospital-college partnership.
Nursing students in Gwinnett Hospital System's summer Nurse Extern Program participated in an innovative initiative that promoted critical thinking, prioritization, and teamwork. A collegial partnership between the Gwinnett Hospital System Learning Resources Department and the Georgia Perimeter College Department of Nursing used simulation as a patient care teaching methodology. Simulation may be one methodology that hospital-college partnerships can pursue in developing and achieving nursing excellence in future nurses.


Harnessing the hydrogen evolution reaction (HER) through the electrical mobility of an embossed Ag(I)-molecular cage and a Cu(II)-coordination polymer.
A structurally characterized porous Ag(I)-molecular cage AgMOC and a Cu(II)-coordination polymer CuCP with a pre-synthesized ligand 1,3-bis(((E)-2-methoxybenzylidene)amino)propan-2-ol and its parental amine with thiocyanate are reported to harness electrical mobility-driven hydrogen evolution activity. Porosity-induced electrically conductive AgMOC emerges as a better electrocatalyst with a Tafel slope of 104 mV per decade over Cu(II)-polymer's slope of 128 mV per decade. The electrochemical stability and durability of the designed electrocatalysts in harnessing the HER activity are also examined under experimental conditions.


Control of thymus-independent intestinal intraepithelial lymphocytes by beta 2-microglobulin.
Murine intestinal intraepithelial lymphocytes (i-IEL) comprise thymus-dependent cells such as T cell receptor (TcR) alpha/beta CD8 alpha/beta+ i-IEL, as well as thymus-independent ones such as TcR alpha/beta CD8 alpha/alpha+ and TcR gamma/delta CD8 alpha/alpha+ i-IEL. Whilst the development of the CD8 alpha/beta expressing i-IEL is strictly contingent on major histocompatibility complex (MHC) class I surface expression, that of CD8 alpha/alpha i-IEL appears largely MHC class I independent. We have used beta 2-microglobulin (beta 2m)-/- mutant mice lacking surface-expressed MHC class I and TcR alpha/beta CD8 alpha/beta+ i-IEL to analyze the potential impact of MHC class I on regional activation of thymus-independent i-IEL. To analyze the role of TcR gamma/delta i-IEL in regional cell interactions, these mice were treated with the anti-TcR gamma/delta mAb, GL3. Whilst numbers of TcR alpha/beta CD8 alpha/alpha i-IEL were markedly reduced in beta 2m-/- mice, those of TcR gamma/delta i-IEL were elevated. Administration of GL3 in vivo caused TcR down-modulation and functional inactivation of TcR gamma/delta i-IEL in beta 2m+/- mice. In contrast, TcR expression and functional activities of TcR gamma/delta i-IEL from beta 2m-/- mice were not impaired by GL3 treatment. The TcR alpha/beta CD8 beta- i-IEL from beta 2m-/- mice were expanded and functionally activated as a consequence of TcR gamma/delta engagement. The TcR gamma/delta i-IEL and TcR alpha/beta CD8 alpha/alpha+ i-IEL from athymic nu/nu mice which express MHC class I, but lack TcR alpha/beta CD8 alpha/beta+ i-IEL, responded to TcR gamma/delta engagement as those from the beta 2m+/- controls. In addition, the TcR gamma/delta i-IEL from TcR beta-/- and TCR beta+/- mutants were equally affected by GL3. We conclude that the absence of beta 2m renders TcR gamma/delta i-IEL resistant to TcR-mediated inactivation and promotes activation of TcR alpha/beta CD8 beta- i-IEL. The activation of TcR gamma/delta i-IEL seems to be directly controlled by beta 2m/MHC class I expression and independent from TcR alpha/beta CD8 beta+ i-IEL. Regulation of self-reactive thymus-independent i-IEL through beta 2m/ MHC class I may contribute to control of autoreactive immune responses in the intestine.


2,3,7,8-Tetrachlorodibenzo-p-dioxin causes unbalanced growth in 5L rat hepatoma cells.
5L cells, dedifferentiated descendents of the rat hepatoma line H4IIEC3, constitute one of the rare continuous lines which are sensitive to the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In the present study we investigated the nature of TCDD toxicity in these cells. The following results were obtained: (1) Exposure to 0.1 nM TCDD for 48 hr inhibits the proliferation of 5L cells by more than 50%, as determined by the increase in the number of cells and the amount of DNA per culture. (2) TCDD doubles the amount of protein and the uptake of neutral red per cell during the 48-hr exposure period. (3) TCDD restores neither constitutive levels of tyrosine aminotransferase, a marker of liver-specific functions, nor its inducibility by dexamethasone. (4) The effects of TCDD are reversible when TCDD-containing growth media are replaced by TCDD-free medium. (5) 5L cells grown at 2% of fetal bovine serum are considerably more sensitive to TCDD than those grown at 10% serum. These results indicate that TCDD inhibits the proliferation of 5L cells without retarding the rate of growth or overtly changing the status of differentiation. The dioxin possibly causes unbalanced cell growth by interfering with the action of hormones or factors contained in the growth medium.


Anxiety and Quality of Life Outcomes After Coronary Artery Bypass Graft Surgery - A Prospective Cohort Study.
Improvements in physical and adaptive psychosocial challenges after Coronary artery bypass grafting (CABG) is unclear to what extent these outcomes impact patients' health-related quality of life. This study was to determine the quality of life among patients 3 months after CABG surgery. More specifically, the study examines the contribution of a set of variables on the quality of life. A prospective cohort study was performed over 3 months among 219 adult patients prepared for elective Coronary Artery Bypass Grafting. The data on the baseline measurements Short Form-36 to measure self-reported health-related quality of life and the state-trait anxiety inventory scale to assess anxiety were collected two days before and three months after CABG surgery. The Pearson correlation coefficient was adopted to examine the relationship between confounding, predictor, and dependent variables. Shapiro-Wilk test tested the normality of the distribution of numerical variables. A 2-tailed level of P-value < 0.05 was set to be statistically significant for all analyses. Mean preoperative postoperative physical and mental component score was 34.57 ± 9.6, 43.53 ± 7 and 54.87 ± 1.19, 51.65 ± 9.67, respectively, indicating poor quality of life. Preoperative anxiety uniquely explained with the variation 32.1% and 29.9% and it significantly predicts postoperative physical health quality of life as (β = .535, t = 8.433, P < 0.001) and postoperative mental health quality of life as (β = .475, t = 7.147, P < 0.001) respectively. Significant improvement in physical health over the 3 months was confirmed, but mental health-related quality of life is unconvincing with the substantial contribution of anxiety.


Interleukin enhancer-binding factor 2 promotes cell proliferation and DNA damage response in metastatic melanoma.
1q21.3 amplification, which is frequently observed in metastatic melanoma, is associated with cancer progression. Interleukin enhancer-binding factor 2 (ILF2) is located in the 1q21.3 amplified region, but its functional role or contribution to tumour aggressiveness in cutaneous melanoma is unknown. In silico analyses were performed using the TCGA SKCM dataset with clinical annotations and three melanoma microarray cohorts from the GEO datasets. RNA in situ hybridisation and immunohistochemistry were utilised to validate the gene expression in melanoma tissues. Four stable melanoma cell lines were established for in vitro ILF2 functional characterisation. Our results showed that the ILF2 copy number variation (CNV) is positively correlated with ILF2 mRNA expression (r = 0.68, p < .0001). Additionally, ILF2 expression is significantly increased with melanoma progression (p < .0001), and significantly associated with poor overall survival for metastatic melanoma patients (p = .026). The overexpression of ILF2 (ILF2-OV) promotes proliferation in metastatic melanoma cells, whereas ILF2 knockdown decreases proliferation by blocking the cell cycle. Mechanistically, we demonstrated the interaction between ILF2 and the splicing factor U2AF2, whose knockdown reverses the proliferation effects mediated by ILF2-OV. Stage IIIB-C melanoma patients with high ILF2-U2AF2 expression showed significantly shorter overall survival (p = .024). Enhanced ILF2/U2AF2 expression promotes a more efficient DNA-damage repair by increasing RAD50 and ATM mRNA expression. Paradoxically, metastatic melanoma cells with ILF2-OV were more sensitive to ATM inhibitors. Our study uncovered that ILF2 amplification of the 1q21.3 chromosome is associated with melanoma progression and triggers a functional downstream pathway in metastatic melanoma promoting drug resistance.


Long-term effect of intermediate particulate matter (PM1-2.5) on incident asthma among middle-aged and elderly adults: A national population-based longitudinal study.
There is insufficient evidence about the long-term effects of intermediate particulate matter (PM1-2.5) on asthma development in adults aged 45 years and above. This study aimed to investigate the relationship between long-term exposure to PM1-2.5 and the incidence of asthma in adults aged 45 years and above. A cohort study based on the China Health and Retirement Longitudinal Study (CHARLS) database was conducted to investigate the long-term effects of PM1-2.5 on self-reported asthma incidence in adults aged 45 years and above in China from 2011 to 2018. The PM concentrations were estimated using a high-resolution (1 km2) satellite-based spatiotemporal model. A covariate-adjusted generalized linear mixed model was used to analyze the relationship between long-term exposure to PM1-2.5 and the incidence of asthma. Effect modifications and sensitivity analysis were conducted. After a 7-year follow-up, 103 (1.61 %) of the 6400 participants developed asthma. Each 10 μg/m3 increment in the 1-, 2-, 3-, and 4-year moving average concentrations of PM1-2.5 corresponded to a 1.82 [95 % confidence interval (CI):1.11-2.98], 1.95 (95 % CI: 1.24-3.07), 1.95 (95 % CI: 1.26-3.03) and 1.88 (95 % CI: 1.26-2.81) fold risk for incident asthma, respectively. A significant multiplicative interaction was observed between socioeconomic level and long-term exposure to PM1-2.5. Stratified analysis showed that smokers and those with lower socioeconomic levels were at higher risk of incident asthma related to PM1-2.5. Restricted cubic splines showed an increasing trend in asthma incidence with increasing PM1-2.5. Sensitivity analyses showed that our model was robust. Long-term exposure to PM1-2.5 was positively associated with incident asthma in middle-aged and elderly individuals. Participants with a history of smoking and lower socioeconomic levels had a higher risk. More studies are warranted warrant to establish an accurate reference value of PM1-2.5 to mitigate the growing asthma burden.


[Early diagnosis of staphylococcic infection in epidural space : radiologic contribution (author's transl)].
Infection of the épidural space was demonstrated on clinic (cauda equina compression) and radiology. Three investigations are considered and compared : Dimer X radiculography, lumbar phlebography, duroliopaque myelography. The transfemoral arcending lumbar catheterization of the epidural veins precise the compression by staphylococcic external pachymeningitis. No liquid is introduced in cerebro spinal fluid : there is not risk of infectious arachnoiditis. Myelography with positive contrast (duroliopaque: ethyl monoiodostearate) is much attractive but it is a procedure not easy to perform, even badly tolerated by the patient. For these reasons the lumbar phlebography, easily performed, can be realised in first intention.


Non-Hodgkin lymphoma (NHL) in children with Nijmegen Breakage syndrome (NBS).
Due to small number of patients with Nijmegen Breakage Syndrome (NBS) and Non-Hodgkin lymphoma (NHL) experience in their treatment is limited. Since 1996, 17 patients with a median age of 9.5 years who had NBS, were treated for NHL. NHL type, stage, chemotherapy, dose modifications, chemotherapy delays, response to chemotherapy, toxicity, outcome and correlation of drug reduction with response to treatment and outcome were analyzed. Nine patients had TNHL, eight BNHL. TNHL patients received BFM and BNHL LMB type protocols. Doses of cytostatics were reduced in the first chemotherapy courses. Further modifications depended on severity of complications. None of the patients complied with timing of chemotherapy. Complete remissions after induction were achieved in 8 of 9 TNHL and 3 out 8 of BNHL patients. All patients experienced grade 4 toxicities. Two patients died from complications. Six of 17 patients are alive. All received more than 80% of recommended doses of chemotherapy. No differences in the type, number of responses or grade 3 and 4 toxicities between patients receiving less or more than 80% of drug doses were observed. Treatment related deaths concerned patients who received less than 80% of drug doses. Patients with NBS develop both T and B cell lymphomas. Treatment outcome is poor and might be improved by administering over 80% of drug doses. Although toxicity often depends upon drug doses, our patients experienced equal grade 3 and 4 toxicities whether they received more or less than 80% of the chemotherapeutic agents.


Improved intra-operative reduction control using a three-dimensional mobile image intensifier - a proximal tibia cadaver study.
This study aimed to analyse whether the precision of a three-dimensional mobile image intensifier (ISO-C 3D) differs from conventional two-dimensional fluoroscopy and high resolution CT scan in a fracture model of the proximal tibia. A depression fracture of the medial plateau (AO/OTA 41-B2.3) was created in 12 formalin-fixed, human cadaver knees. The cartilage of the depression could be positioned above (+1mm, +2mm), below (-1mm, -2mm), or in line with the joint surface. Fluoroscopy, computed tomography (CT) scans, and ISO-C 3D scans (four different protocols: 100 images, 66 images, 50 images, and 33 images) were done for each fracture level. Three independent observers assessed each imaging set. The difference between the estimated reduction and the real reduction was used for statistical analysis. Our hypothesis was that no differences in the precision exist between the imaging techniques (p<0.05). The conventional image intensifier group (0.7 mm+/-0.67) showed significantly higher deviations than the CT group (0.3 mm+/-0.43; p<0.001) and significantly higher deviations than all ISO-C 3D groups (0.4-0.5 mm; p<0.001). Of the ISO-C 3D groups, only the scan protocol with the lowest number of images (0.5 mm+/-0.51) showed significantly lower precision than the CT group (p<0.001). It was concluded that the three-dimensional mobile image intensifier showed higher precision in reduction assessment in a fracture model of the tibial plateau compared to fluoroscopy. High resolution CT scans should remain the standard for post-operative assessment of reduction outside the operating theatre.


In vivo protective effect of protocatechuic acid on tert-butyl hydroperoxide-induced rat hepatotoxicity.
Increasing evidence regarding free-radical generating agents and the inflammatory process suggests that accumulation of reactive oxygen species (ROS) can involve hepatotoxicity. Previously, we found that protocatechuic acid (PCA), a polyphenolic compound from Hibiscus sabdariffa L. possessing free radical-scavenging capacity, protected against oxidative damage induced by tert-butylhydroperoxide (t-BHP) in rat primary hepatocytes. In this study, first PCA was evaluated by its capacity of inhibiting xanthine oxidase (XO) and lipoxygenase (LO) activity in vitro, then it was used to induce hepatotoxicity to assess the antioxidant and anti-inflammatory bioactivity of PCA in vivo. Our investigation showed that pretreatment with PCA (50-100 mg/kg) by gavage for 5 days before a single dose of t-BHP (ip; 0.2 mmol/kg ) significantly lowered serum levels of the hepatic enzyme markers lactate dehydrogenase (LDH) and alanine (ALT) and aspartate (AST) aminotransferase, and reduced oxidative stress of the liver by evaluating malondialdehyde (MDA) and glutathione (GSH). Histopathological evaluation of the rat livers revealed that PCA reduced the incidence of liver lesions, including hepatocyte swelling, leukocyte infiltration, and necrosis induced by t-BHP. In addition, PCA inhibited t-BHP-induced tyrosine phosphorylation, an implication of the activation of a stress signal pathway, in the liver. These results indicate that PCA protects against t-BHP-induced hepatotoxicity by its antioxidant and anti-inflammatory characteristics accompanied by blocking of stress signal transduction.


The protease inhibitory properties of the Alzheimer's beta-amyloid precursor protein.
We have expressed the 57-amino acid Kunitz domain of the Alzheimer's beta-amyloid precursor protein (APP751) as a bacterial fusion protein. The protease inhibitory properties of the purified fusion protein, BX9, were virtually identical in all respects tested to those of purified secreted APP751. Both proteins strongly inhibited pancreatic trypsin (Kis = 0.2 and 0.3 nM) and less well epidermal growth factor-binding protein (Kis = 1 and 3.5 nM), alpha-chymotrypsin (Kis = 3 and 6 nM), and the gamma-subunit of nerve growth factor (Kis = 8 and 9 M). Neither protein appreciably inhibited plasma and pancreatic kallikreins, thrombin, lung tryptase, neutrophil elastase, or cathepsin G. The remarkable similarity of the protease inhibitory profile of BX9 to that of secreted APP751 suggests that proper intramolecular disulfide bond formation has occurred in the bacterial fusion protein and leads to the conclusion that the amyloid precursor protein Kunitz domain is a relatively specific inhibitor of only a few trypsin-like arginine esterases.


Three-dimensional cardiac tissue image registration for analysis of in vivo electrical mapping.
A method is presented for registering 3D cardiac tissue images to reference data, for the purpose of analyzing recorded electrical activity. Following left-ventricular in vivo electrical mapping studies in pig hearts, MRI is used to define a reference geometry in the tissue segment around the recording electrodes. The segment is then imaged in 3D using a high-resolution serial imaging microscopy technique. The tissue processing required for this introduces segment-wide distortion. Piecewise-smooth maps are used to correct the tissue distortion and register the 3D images with the reference MRI data. The methods are validated and techniques for identifying the preferred maps are proposed. Recorded electrical activation is shown to map reliably onto cardiac tissue structure using this registration method.


Relationships between drug concentrations in serum and CSF, clinical effects and monoaminergic variables in schizophrenic patients treated with sulpiride or chlorpromazine.
Schizophrenic patients were treated with fixed doses of sulpiride (800 mg) or chlorpromazine (400 mg) during eight weeks using a double-blind design. In order to examine relationships between pharmacokinetic, clinical and biochemical parameters in relation to treatment the following variables were recorded before and 1, 2, 4 and 8 weeks after treatment. Concentrations of sulpiride, CPZ, 7-OH-CPZ, nor1-CPZ were determined in serum and CSF using liquid chromatography and mass fragmentography. Clinical variables were psychotic morbidity and side effects as evaluated by CPRS, NOSIE and side effect ratings. Monoaminergic variables were concentrations of the major cerebral monoamine metabolites, HVA, 5-HIAA and MOPEG in the cerebrospinal fluid as measured by mass fragmentography. Prolactin levels in serum and CSF were measured by radioimmunoassay. During steady state, concentrations of sulpiride in serum varied fourfold between patients and CPZ twentyfold. Drug concentrations in serum and CSF were highly correlated in CPZ-but not in sulpiride-treated patients. Although sulpiride passed into the CSF, transport between serum and CSF was restricted. In the sulpiride group, improvement of psychotic morbidity and HVA elevation in CSF tended to be negatively related to the drug concentrations in serum. Sulpiride-treated patients with extrapyramidal side effects had significantly higher drug concentrations in serum. In CPZ-treated patients, improvement of psychotic morbidity, HVA elevation and prolactin elevation all tended to be positively correlated to drug concentrations in serum and CSF. CPZ-treated patients with extrapyramidal side effects also had significantly higher CPZ concentrations in serum. In both treatment groups, the MOPEG reduction in CSF tended to be correlated to improvement of psychotic morbidity. The study supplied clinical evidence for the view that antipsychotic drugs belonging to the phenothiazine and benzamide series induce antipsychotic effects in schizophrenic patients in a graded fashion which is proportional to the degree of interaction with the central dopaminergic mechanisms. The results also support the view that sulpiride has a more selective effect on central dopaminergic mechanisms than chlorpromazine. In the schizophrenic patients studied and with the doses used, sulpiride concentrations tended to be maximal with regard to clinical and biochemical effects. For CPZ on the other hand, drug concentrations in some patients seemed to be too low to induce optimal effects.


Inpatient treatment for substance abuse patients with psychiatric disorders: a national study of determinants of readmission.
This study examined the patient case mix and program determinants of 6-month readmission rates and early treatment dropout for 7,711 VA inpatients with both substance abuse and major psychiatric disorders treated in one of 104 substance abuse programs. Patients were treated in one of three types of inpatient programs: explicitly designed dual diagnosis specialty programs, substance abuse programs with a dual diagnosis psychotherapy group or standard substance abuse programs. Dual diagnosis specialty programs differed from regular substance abuse programs in that they had a more severe case mix, a higher 180-day readmission rate, greater dual diagnosis treatment orientation, used more psychotropic medication, had longer lengths of stay, had greater tolerance of relapse and medication noncompliance, and a higher rate of psychiatric aftercare in the 30 days after discharged. Programs with less severe case mix, longer intended and actual length of stay, lower 7-day dropout rates, greater tolerance of problem behavior, 12-step groups, and higher immediate postdischarge utilization of outpatient mental health treatment lower 180-day readmission rates. Programs with less severe patient case mix, more use of psychotropic medications but less of methadone and antabuse, less varied and diverse treatment activities, and low use of patient-led groups had lower dropout rates.


Structures of inclusion complexes of halogenbenzoic acids and alpha-cyclodextrin based on AM1 calculations.
Semi-empirical quantum mechanics calculations using AM1 (Austin Method 1) were carried out for various host-guest combinations of alpha-cyclodextrin and mono-halogen benzoic acids. The energetically favorable inclusion structures were identified. The AM1 results show that alpha-cyclodextrin complexes with mono-halogen benzoic acid acids (where the halogen is chlorine, bromide, iodine) as guest compounds are more stable in the "head first" position than in the "tail-first" position for meta and para isomers while ortho mono-halogen benzoic acids complexes with alpha-cyclodextrin are more stable in "tail-first" position. The calculated structures were found to be in good agreement with those obtained from crystallographic databases.


The effect of hydrophilic chain length and iRGD on drug delivery from poly(ε-caprolactone)-poly(N-vinylpyrrolidone) nanoparticles.
Poly(ε-caprolactone)-b-Poly(N-vinylpyrrolidone) (PCL-b-PVP) copolymers with different PVP block length were synthesized by xanthate-mediated reverse addition fragment transfer polymerization (RAFT) and the xanthate chain transfer agent on chain end was readily translated to hydroxy or aldehyde for conjugating various functional moieties, such as fluorescent dye, biotin hydrazine and tumor homing peptide iRGD. Thus, PCL-PVP nanoparticles were prepared by these functionalized PCL-b-PVP copolymers. Furthermore, paclitaxel-loaded PCL-PVP nanoparticles with satisfactory drug loading content (15%) and encapsulation efficiency (>90%) were obtained and used in vitro and in vivo antitumor examination. It was demonstrated that the length of PVP block had a significant influence on cytotoxicity, anti-BSA adsorption, circulation time, stealth behavior, biodistribution and antitumor activity for the nanoparticles. iRGD on PCL-PVP nanoparticle surface facilitated the nanoparticles to accumulate in tumor site and enhanced their penetration in tumor tissues, both of which improved the efficacy of paclitaxel-loaded nanoparticles in impeding tumor growth and prolonging the life time of H22 tumor-bearing mice.


Effect of oral treatment with (S)-HPMPA, HDP-(S)-HPMPA or ODE-(S)-HPMPA on replication of murine cytomegalovirus (MCMV) or human cytomegalovirus (HCMV) in animal models.
We utilized BALB/c mice infected with murine CMV (MCMV) or severe combined immunodeficient (SCID) mice implanted with human fetal tissue and infected with HCMV to determine the efficacy of (S)-9-[3-hydroxy-2-(phophonomethoxy)propyl]adenine ((S)-HPMPA), hexadecyloxypropyl-(S)-HPMPA (HDP-(S)-HPMPA) or octadecyloxyethyl-(S)-HPMPA (ODE-(S)-HPMPA). In MCMV-infected BALB/c mice, oral HDP-(S)-HPMPA at 30 mg/kg significantly reduced mortality when started 24-48 h post inoculation. In the experimental HCMV infection, oral administration of vehicle or 10mg/kg of (S)-HPMPA, HDP-(S)-HPMPA or ODE-(S)-HPMPA was initiated 24h after infection and continued for 28 consecutive days. Cidofovir (CDV), at 20mg/kg given i.p., was used as a positive control. HDP-(S)-HPMPA or ODE-(S)-HPMPA significantly reduced viral replication compared to vehicle-treated mice, while oral (S)-HPMPA was ineffective.


Cross-Cover Curriculum for Senior Medical Students.
Cross-cover, the process by which a nonprimary team physician cares for patients, usually during afternoons, evenings, and weekends, is common in academic medical centers. With the advent of residency duty-hour restrictions, cross-cover care has increased, making education in effective cross-coverage an urgent need. We implemented a cross-cover didactic activity composed of 18 interactive cases with 29 senior medical students enrolled in an internal medicine residency preparation course. The curriculum was facilitated by one faculty member and one senior medical resident and utilized think-pair-share learning techniques to discuss an approach to a range of common (both urgent and routine) cross-cover scenarios. We analyzed confidence and feelings of preparedness pre- and postintervention. We also examined differences in medical knowledge based on two multiple-choice written cross-cover cases that addressed both medical management and triage. This curriculum significantly improved feelings of confidence (from 1.8 to 3.2, p < .0001), reduced anxiety (from 4.5 to 4.1, p < .03), and improved performance in clinical case scenarios (from 82% to 89%, p < .02). This curriculum covered not only the important medical aspects of cross-cover care (e.g., diagnostics and management) but also equally important roles of cross-cover, such as how to effectively triage cross-cover scenarios. The curriculum was well received by students.


Academy of Nutrition and Dietetics: Revised 2020 Standards of Practice and Standards of Professional Performance for Registered Dietitian Nutritionists (Competent, Proficient, and Expert) in Intellectual and Developmental Disabilities.
Intellectual and developmental disabilities (IDD) encompass both intellectual disabilities (ID) and developmental disabilities (DD). In 2016, 7.37 million people in the United States and 200 million worldwide were identified with an ID or DD. Approximately 1 in 6 (17.8%) children have been identified with a DD in the United States, which is up from 16.2% in 2009-2011. Globally, 52.9 million children from birth to 5 years of age have been identified with a DD. Registered dietitian nutritionists (RDNs) have an important role in the treatment of this population, as optimizing nutrition status improves cognition and quality of life. The Behavioral Health Nutrition Dietetic Practice Group, with guidance from the Academy of Nutrition and Dietetics Quality Management Committee, has revised the Standards of Practice (SOP) and Standards of Professional Performance (SOPP) for RDNs in Intellectual and Developmental Disabilities for 3 levels of practice-competent, proficient, and expert. The SOP uses the Nutrition Care Process and clinical workflow elements for care of individuals with an ID or DD. The SOPP describes 6 domains that focus on professionalism. Indicators outlined in the SOP and SOPP depict how these standards apply to practice. The SOP and SOPP are complementary resources for RDNs caring for individuals with an ID or DD. The SOP and SOPP are intended to be used by RDNs for self-evaluation to assure competent practice and for determining potential education and training needs for advancement to a higher practice level in a variety of settings.


Calcium and mitochondrial metabolism in ceramide-induced cardiomyocyte death.
Ceramides are important intermediates in the biosynthesis and degradation of sphingolipids that regulate numerous cellular processes, including cell cycle progression, cell growth, differentiation and death. In cardiomyocytes, ceramides induce apoptosis by decreasing mitochondrial membrane potential and promoting cytochrome-c release. Ca(2+) overload is a common feature of all types of cell death. The aim of this study was to determine the effect of ceramides on cytoplasmic Ca(2+) levels, mitochondrial function and cardiomyocyte death. Our data show that C2-ceramide induces apoptosis and necrosis in cultured cardiomyocytes by a mechanism involving increased Ca(2+) influx, mitochondrial network fragmentation and loss of the mitochondrial Ca(2+) buffer capacity. These biochemical events increase cytosolic Ca(2+) levels and trigger cardiomyocyte death via the activation of calpains.


Gene expression perturbation in vitro--a growing case for three-dimensional (3D) culture systems.
Cells grown in vitro are dramatically perturbed by their new microenvironment. Analyses of genome-wide gene expression levels offer a first glance at which genes and pathways are affected in cell lines as compared to their tissues of origins. We have summarized available gene expression data and review how cell lines adapt to in vitro environments, to what degree they express markers of their tissues of origins and discuss how cells grown in three-dimensional (3D) cultures may have more physiological interactions with neighbouring cells and extracellular matrix. We will also discuss the interplay between malignant cells and stroma present in tumours but lacking in cell lines and how these differences might affect gene expression comparisons of cell lines to tumours. A model simulating impact of stromal cells on gene expression profiles is presented. Understanding the transcriptomes of cells grown in 2D and 3D cultures and how they compare to those of in vivo cells are important for improving cell line model systems and for the reconstituting of tissues in vitro.


Comparing adaptation strategies in MRI-guided online adaptive radiotherapy for prostate cancer: Implications for treatment margins.
To quantify the difference in accuracy of adapt-to-position (ATP), adapt-to-rotation (ATR) and adapt-to-shape (ATS) workflows used in MRI-guided online adaptive radiotherapy for prostate carcinoma (PCa) by evaluating the margins required to accommodate intra-fraction motion of the clinical target volumes for prostate (CTVpros), prostate including seminal vesicles (CTVpros + sv) and gross tumor volume (GTV). Clinical delineations of the CTVpros, CTVpros + sv and GTV of 24 patients with intermediate- and high-risk PCa, treated using ATS on a 1.5 T MR-Linac, were used for analysis. Delineations were available pre- and during beam-on. To simulate ATP and ATR workflows, we automatically generated the structures associated with these workflows using rigid transformations from the planning-MRI to the daily online MRIs. Clinical GTVs were analyzed as ATR GTVs and only ATP GTVs were simulated. Planning target volumes (PTVs) were generated with isotropic margins ranging 0.0-5.0 mm. The volumetric overlap was calculated between these PTVs and their corresponding clinical delineation on the MRI acquired during beam-on and averaged over all treatment fractions. The PTV margin required to cover > 95% of the CTVpros was equal (2.5 mm) for all workflows. For the CTVpros + sv, this margin increased to 5.0, 4.0 and 3.5 mm in the ATP, ATR and ATS workflow, respectively. GTV coverage improved from ATP to ATR for margins up to 4.0 mm. ATP, ATR and ATS workflows ensure equal coverage of the CTVpros for the current clinical margins. For the CTVpros + sv, ATS showed optimal performance. GTV coverage improves by additional adaptations to prostate rotations.


Synergies and gaps between circularity assessment and Life Cycle Assessment (LCA).
This article evaluates the synergies between circularity assessment and Life Cycle Assessment (LCA) by investigating their alignments, misalignments, and challenges in addressing sustainability. The analysis emphasizes the significance of a multi-level approach, positioning these methods at various levels, including philosophy, strategy, assessment, and communication. The findings demonstrate that both LCA and circularity assessment can serve as sustainability assessment methods for circularity strategies, despite existing gaps. However, neither approach can provide a complete picture of a system's environmental performance on its own. Data availability, diverse assumptions, spotlights and shadows (highlighted and neglected elements), multiple life cycles, products, functions, strategies, and as well as temporal aspects are identified as the main challenges in addressing sustainability. This article provides recommendations based on the lessons learned from each approach, suggesting the integration of their strengths and addressing challenges to achieve a comprehensive understanding of environmental sustainability and make informed decisions for a circular and sustainable future. These recommendations include using function-based models and the principles of prospective and dynamic LCAs for the development of future circularity assessments. Additionally, circularity assessment can be used to establish LCA models, aiding in identifying hotspots during the goal and scope definition, and determining allocation and weighting factors in both Life Cycle Inventory (LCI) and Life Cycle Impact Assessment (LCIA).


On some paleopathological examples of amputation and the implications for healthcare in 13th-17th century Lithuania.
To explore care that was likely provided to an adult male amputee from medieval Lithuania, positioning analysis within what is known of contemporary amputation practices. Three sets of skeletal remains with evidence for amputation, dating to between the 13th-17th centuries AD and recovered during different archaeological excavations in Vilnius, Lithuania. Macroscopic inspection of lesions, with additional X-ray analysis of the main subject. The Index of Care was used to investigate possible caregiving. Two individuals experienced amputation of a single element, and the third experienced bilateral hand amputation. Only one individual displayed healing. Historic sources suggest use of amputation for punitive purposes during this period, and judicial punishment is proposed as the most likely reason for amputation in at least two cases. Evidence of long-term healing in one individual suggests receipt of care. This individual likely relied on family and/or community members for survival immediately following amputation, and subsequently for support in managing disability. Successfully combining osteology with history in a framework for analyzing care provision in past Eastern European society, this study underlines the critical importance of context in undertaking bioarchaeology of care analyses. It also adds two examples of perimortem abscissions in this region to the paleopathological record. Our approach relied on skeletal interpretation. Soft tissue was lost to decomposition and no relevant archaeological evidence was found in association with the remains. A review of skeletal collections may allow identification of overlooked cases of amputation (and care).


Subject-specific finite element analysis of a lumbar cage produced by electron beam melting.
The aim of this study was the analysis of the mechanical behaviour of a partially porous lumbar custom-made cage by means of a subject-specific finite element analysis (FEA). The cage, made of Ti6Al4V ELI alloy, was produced via electron beam melting (EBM) process and surgically implanted in a female subject, 50 years old. The novelty of this study was the customized design of the cage and of its internal structure, which is impossible to obtain with the traditional production techniques. The 3D model of the spine was obtained from the computed tomography (CT) of the patient. Moreover, high-resolution industrial CT was also used to reconstruct a 3D model of the cage, with its real (as-produced) features, such as superficial roughness, morphology of the bulk and of the porous structure. The workflow was divided in several steps: the main finite element analyses were non-linear and quasi-static regarding: the rhombic dodecahedron (RD) unit cell of the porous structure; the device; the whole L4-L5 motion segment with the implanted cage. Stress distribution was calculated under compression load for all models. For the RD unit cell, the maximum stress appeared at the connected cross nodes, where notch effect was present. For the cage subjected to a load of 1 kN, the porous structure did not present any functional failure. For the whole biomechanical system subjected to a physiological load of 360 N, the calculated stress in the bone was smaller than its yield strength value. On the axial view, a zone with higher compressive stresses was present on the L5 vertebral body. This was due to the contact stress between the cage and the vertebra. From the comparison between FE results and the CT images of the spine, bone remodelling was supposed, with the formation of new bone. Graphical abstract Workflow showing the phases of the research.


A new case of an Holarctic element in the Colombian Andes: first record of Cordyla Meigen (Diptera, Mycetophilidae) from the Neotropical region.
Three new species of Mycetophilidae - Cordyla monticola sp. n., Cordyla pseudopusilla sp. n. and Cordyla reducta sp. n. - are described from the Colombian Andes, representing the first described species of Cordyla Meigen from the Neotropical region. Colour photos of their habitus, wing and terminalia are provided. The morphological affinities of male terminalia are discussed in a worldwide context. The distributional pattern of the genus clearly indicates a case of northern elements reaching the north-western region of the Neotropics that corresponds to a secondary extension of a Holarctic clade to the south.


Trends of delays in tuberculosis case finding in Japan and associated factors.
Nationwide tuberculosis (TB) registry in Japan, 1987-2002. To clarify the trends of patient's delay (PD), doctor's delay (DD) and total delay (TD), their relation and factors associated with the delays. Longitudinal study on trends in delays. Among patients with symptomatic smear-positive pulmonary TB, those with long PD (> or =2 months), DD (> or =1 month) and TD (> or =3 months) were analysed. Long PD rates increased until around 1997, whereas long DD rates decreased markedly from 1995 to 1999. Long TD rates increased until 1997, and decreased slightly thereafter. Men aged 30-59 years had higher rates of long PD, and the long PD rates increased through the 16-year observation period. Day labourers receiving or applying for welfare benefit had the highest rate of long TD, 46.5% during 1995-2002. Teachers and medical doctors showed the greatest increase in long TD rates through the period. Long TD was influenced more by PD than DD, and showed an upward trend. However, the long TD rate has declined slightly owing to the recent reduction in long DD. The reduction in DD since 1995 occurred immediately after the introduction of new technology in bacteriological examinations.


How New Developments Impact Diagnosis in Existing Renal Neoplasms.
In recent years, several emerging diagnostic entities have been described in renal cell carcinoma (RCC). However, our understanding of well-known and established entities has also grown. Clear cell papillary RCC is now relabeled as a tumor rather than carcinoma in view of its nonaggressive behavior. Renal tumors with a predominantly infiltrative pattern are very important for recognition, as most of these have aggressive behavior, including fumarate hydratase-deficient RCC, SMARCB1-deficient medullary carcinoma, collecting duct carcinoma, urothelial carcinoma, and metastases from other cancers.


Early life sun exposure, vitamin D-related gene variants, and risk of non-Hodgkin lymphoma.
It has been hypothesized that vitamin D mediates the inverse relationship between sun exposure and non-Hodgkin lymphoma (NHL) risk reported in several recent studies. We evaluated the association of self-reported sun exposure at ages <13, 13-21, 22-40, and 41+ years and 19 single nucleotide polymorphisms (SNPs) from 4 candidate genes relevant to vitamin D metabolism (RXR, VDR , CYP24A1, CYP27B1) with NHL risk. This analysis included 1,009 newly diagnosed NHL cases and 1,233 frequency-matched controls from an ongoing clinic-based study. Odds ratios (OR), 95 % confidence intervals (CI), and tests for trend were estimated using unconditional logistic regression. There was a significant decrease in NHL risk with increased sun exposure at ages 13-21 years (OR(≥15 vs. ≤3 h/week) = 0.68; 95 % CI, 0.43-1.08; p(trend) = 0.0025), which attenuated for older ages at exposure. We observed significant main effect associations for 3 SNPs in VDR and 1 SNP in CYP24A1: rs886441 (OR(per-allele) = 0.82; 95 % CI, 0.70-0.96; p = 0.016), rs3819545 (OR(per-allele) = 1.24; 95 % CI, 1.10-1.40; p = 0.00043), and rs2239186 (OR(per-allele) = 1.22; 95 % CI, 1.05-1.41; p = 0.0095) for VDR and rs2762939 (OR(per-allele) = 0.85; 95 % CI, 0.75-0.98; p = 0.023) for CYP24A1. Moreover, the effect of sun exposure at age 13-21 years on overall NHL risk appears to be modified by germline variation in VDR (rs4516035; p(interaction) = 0.0066). Exploratory analysis indicated potential heterogeneity of these associations by NHL subtype. These results suggest that germline genetic variation in VDR, and therefore the vitamin D pathway, may mediate an association between early life sun exposure and NHL risk.


Facile synthesis of the indeno-tetrahydropyridine core of haouamine A.
[reaction: see text] The tricyclic indeno-tetrahydropyridine core of haouamine A, containing five of the seven rings of the natural product, was constructed by a simple, concise route that features an acid-catalyzed Friedel-Crafts ring closure.


Shedding light on gibberellic acid signalling.
Gibberellic acid (GA) promotes a range of developmental and growth processes in plants, the most well-known being germination, elongation growth and flowering time. DELLA repressors are the key players of the pathway. Their presence or their GA-dependent turnover via the 26S proteasome correlates to a large extent with the repression or derepression, respectively, of GA-dependent growth responses. Recent progress has revealed the role of DELLA repressors in several novel response pathways, and at the biochemical level, they have now been shown to function as repressors of the PHYTOCHROME INTERACTING FACTOR3 (PIF3) and PIF4 transcriptional activators in the context of light-regulated seedling development. Furthermore, the first insights have been gained into the evolution of the GA signalling pathway on the basis of comparative genomics between the moss Physcomitrella patens, the lycophyte Selaginella moellendorffii and seed plants.


Liquid chromatographic analysis of alizapride and metoclopramide in human plasma and urine using solid-phase extraction.
A universal rapid, sensitive and selective high-performance liquid chromatographic method with UV detection at 230 nm has been developed for the determination of benzamide drugs in human plasma and urine. Sample pretreatment is carried out using solid-phase extraction columns, resulting in very high extraction recoveries of the compounds investigated (alizapride, metoclopramide, alpiropride, amisulpride). The detector response is linear from 25 to 10,000 ng/ml, and the detection limit is 3 ng/ml for alizapride and 10 ng/ml for metoclopramide. The proposed method is highly suitable for pharmacokinetic studies and for drug monitoring.


[Fall events in geriatric hospital in-patients. Results of prospective recording over a 3 year period].
For a period of 3 consecutive years, all fall events were prospectively recorded in geriatric hospital in-patients by using a standardized protocol. The incidence was 9.1 fall events/1000 hospital days in 5946 patients, and 41.0/1000 hospital days in 1015 patients (17.0%) who actually had falls. The fall rate varied between 35.0-57.0/1000 hospital days according to the main diagnostic group. Fall events were more often recorded in men than women. Recurrent falls (> or =3 falls) which contributed 13% to the 1596 falls were recorded more frequently in male patients. The majority of fall events (73.5%) occurred in patient rooms, another 20% on the floor between the patient's bedroom and toilet/bath, or in the toilet/bath, respectively. The absolute numbers of falls during night and day were not different. However, there were different patterns in the time distribution of high fall frequencies according to the main diagnostic groups. Confusion and dehydration were recorded more frequently with fall events in patients 80 years and older, and more often in fall events during the night. Injuries due to falls which had to be treated were rare, and fall-related fractures were very rare. The average duration of in-hospital stay was longer for patients with than without falls.


Consanguinity and schizophrenia in Sudan.
The rate of first-cousin marriages among the patients of schizophrenics was compared with a control group in an isolated highly inbred sudanese community, no significant difference being found.


Effect of sol-gel transition of oil phase (O) and inner aqueous phase (W1) on the physical and chemical stability of a model PUFA rich-W1/O/W2 double emulsion.
In this study, the effect of sol-gel transition of oil phase (O) and inner aqueous phase (W1) on the physical and chemical stability of a model PUFA rich-W1/O/W2 double emulsion (DE) was investigated. Thermal-driven gelation of O and W1 was performed using monoglyceride and κ-carrageenan, respectively. To accelerate lipid oxidation, ferrous sulfate was encapsulated in W1. Using this approach, O gelation reduced the volume-weighted size (d4,3) of DEs droplets and provided good physical stability. However, non-gelled DEs and those containing gelled W1 exhibited extensive flocculation and coalescence. Moreover, oleogelation resulted in a predominant elastic behavior with weak frequency dependence of viscoelastic properties. Oxidation was significantly reduced by W1 gelation; however, the O gelation led to a higheroxidation rate. Oxidation kinetic parameters induced by a hydrophilic (gallic acid) and a lipophilic (α-tocopherol) antioxidant showed that DEs containing gelled O droplets presented high physical and oxidative stability when α-tocopherol was present.


Effect of acute and chronic 17 beta-estradiol treatment on serotonin and 5-hydroxyindole acetic acid content of discrete brain nuclei of ovariectomized rat.
Increased serotonin content of the dorsal raphe nucleus and of the substantia nigra were seen following acute (12 h or 24 h) administration of 17 beta-estradiol to ovariectomized rats. No changes were seen in numerous other nuclei of forebrain or hindbrain, and no changes occurred during chronic (1 month) estradiol administration. Changes in the concentration of the major serotonin metabolite, 5-hydroxyindole acetic acid, paralleled those of serotonin. These results show that, under precisely defined conditions and in specific locations only, estradiol can modulate serotonergic neuronal systems.


The effect of different morphological sampling criteria on the fraction of bursting cells recorded in the rat subiculum in vitro.
In spite of the large variability of the fraction of bursting cells reported in the subiculum (from 54 to 100%), this structure has been considered as intrinsically bursting. Here, using visually assisted whole-cell recordings and Neurobiotin labeling in vitro, we correlated the electrophysiological firing modes of subicular cells (bursting, regular-spiking and fast-spiking) with their morphological characteristics (somatic size and shape). We then examined how different morphological sampling criteria for patching affect cell classification. We found a dramatic variability in the fraction of bursting cells, which ranged from 30 to 76% depending on the sampling criteria. We discuss the implications of these findings for the notion of the subiculum as an intrinsically bursting structure.


Taking the pulse: Bacterial responses to intermittent antibiotics.
Bacterial species respond differently to consecutive antibiotic exposures with potential consequences on the host microbiome. In this issue of Cell Host & Microbe, Münch et al. investigate the effects of intermittent antibiotic treatments on specific bacteria using a consortium of microbes comprising a functional intestinal microbiota in germ-free mice.


Single Ad26.COV2.S booster dose following two doses of BBIBP-CorV vaccine against SARS-CoV-2 infection in adults: Day 28 results of a phase 1/2 open-label trial.
The inactivated COVID-19 whole-virus vaccine BBIBP-CorV has been extensively used worldwide. Heterologous boosting after primary vaccination can induce higher immune responses against SARS-CoV-2 than homologous boosting. The safety and immunogenicity after 28 days of a single Ad26.COV2.S booster dose given at different intervals after 2 doses of BBIBP-CorV are presented. This open-label phase 1/2 trial was conducted in healthy adults in Thailand who had completed 2-dose primary vaccination with BBIBP-CorV. Participants received a single booster dose of Ad26.COV2.S (5 × 1010 virus particles) 90-240 days (Group A1; n = 360) or 45-75 days (Group A2; n = 66) after the second BBIBP-CorV dose. Safety and immunogenicity were assessed over 28 days. Binding IgG antibodies to the full-length pre-fusion Spike and anti-nucleocapsid proteins of SARS-CoV-2 were measured by enzyme-linked immunosorbent assay. The SARS-CoV-2 pseudovirus neutralization assay and live virus microneutralization assay were used to quantify the neutralizing activity of antibodies against ancestral SARS-CoV-2 (Wuhan-Hu-1) and the delta (B.1.617.2) and omicron (B.1.1.529/BA.1 and BA.2) variants. The cell-mediated immune response was measured using a quantitative interferon (IFN)-γ release assay in whole blood. Solicited local and systemic adverse events (AEs) on days 0-7 were mostly mild, as were unsolicited vaccine-related AEs during days 0-28, with no serious AEs. On day 28, anti-Spike binding antibodies increased from baseline by 487- and 146-fold in Groups A1 and A2, and neutralizing antibodies against ancestral SARS-CoV-2 by 55- and 37-fold, respectively. Humoral responses were strongest against ancestral SARS-CoV-2, followed by the delta, then the omicron BA.2 and BA.1 variants. T-cell-produced interferon-γ increased approximately 10-fold in both groups. A single heterologous Ad26.COV2.S booster dose after two BBIBP-CorV doses was well tolerated and induced robust humoral and cell-mediated immune responses measured at day 28 in both interval groups. NCT05109559.


Fast 180° magnetization switching in a strain-mediated multiferroic heterostructure driven by a voltage.
Voltage-driven 180° magnetization switching provides a low-power alternative to current-driven magnetization switching widely used in spintronic devices. Here we computationally demonstrate a promising route to achieve voltage-driven in-plane 180° magnetization switching in a strain-mediated multiferroic heterostructure (e.g., a heterostructure consisting of an amorphous, slightly elliptical Co40Fe40B20 nanomagnet on top of a Pb(Zr,Ti)O3 film as an example). This 180° switching follows a unique precessional path all in the film plane, and is enabled by manipulating magnetization dynamics with fast, local piezostrains (rise/release time <0.1 ns) on the Pb(Zr,Ti)O3 film surface. Our analyses predict ultralow area energy consumption per switching (~0.03 J/m(2)), approximately three orders of magnitude smaller than that dissipated by current-driven magnetization switching. A fast overall switching time of about 2.3 ns is also demonstrated. Further reduction of energy consumption and switching time can be achieved by optimizing the structure and material selection. The present design provides an additional viable route to realizing low-power and high-speed spintronics.


A chemical genetic screen for direct v-Src substrates reveals ordered assembly of a retrograde signaling pathway.
Using an ATP analog that is a specific substrate for an analog-specific allele of v-Src, we identified several novel cytoskeletal substrates that control actin assembly processes. A screen for less abundant v-Src substrates revealed the scaffolding protein Dok-1 as a direct substrate of v-Src. Further studies suggest that v-Src phosphorylation sites on Dok-1 are critical for its binding to RasGAP and Csk, negative regulators of Src signaling. This results in the downregulation of growth-promoting signals of the Src family kinases and the Ras pathway. Identification of the direct substrates of v-Src leads to a model for the precise order of assembly of a retrograde signaling pathway in v-Src-transformed cells and has provided new insight into the balance between those signals that promote cell transformation mediated by v-Src catalyzed tyrosine phosphorylation and those that inhibit it.


Neural network-based QSAR and insecticide discovery: spinetoram.
Improvements in the efficacy and spectrum of the spinosyns, novel fermentation derived insecticide, has long been a goal within Dow AgroSciences. As large and complex fermentation products identifying specific modifications to the spinosyns likely to result in improved activity was a difficult process, since most modifications decreased the activity. A variety of approaches were investigated to identify new synthetic directions for the spinosyn chemistry including several explorations of the quantitative structure activity relationships (QSAR) of spinosyns, which initially were unsuccessful. However, application of artificial neural networks (ANN) to the spinosyn QSAR problem identified new directions for improved activity in the chemistry, which subsequent synthesis and testing confirmed. The ANN-based analogs coupled with other information on substitution effects resulting from spinosyn structure activity relationships lead to the discovery of spinetoram (XDE-175). Launched in late 2007, spinetoram provides both improved efficacy and an expanded spectrum while maintaining the exceptional environmental and toxicological profile already established for the spinosyn chemistry.


Altered levels of CSF proteins in patients with FTD, presymptomatic mutation carriers and non-carriers.
The clinical presentations of frontotemporal dementia (FTD) are diverse and overlap with other neurological disorders. There are, as of today, no biomarkers in clinical practice for diagnosing the disorders. Here, we aimed to find protein markers in cerebrospinal fluid (CSF) from patients with FTD, presymptomatic mutation carriers and non-carriers. Antibody suspension bead arrays were used to analyse 328 proteins in CSF from patients with behavioural variant FTD (bvFTD, n = 16) and progressive primary aphasia (PPA, n = 13), as well as presymptomatic mutation carriers (PMC, n = 16) and non-carriers (NC, n = 8). A total of 492 antibodies were used to measure protein levels by direct labelling of the CSF samples. The findings were further examined in an independent cohort including 13 FTD patients, 79 patients with Alzheimer's disease and 18 healthy controls. We found significantly altered protein levels in CSF from FTD patients compared to unaffected individuals (PMC and NC) for 26 proteins. The analysis show patterns of separation between unaffected individuals and FTD patients, especially for those with a clinical diagnosis of bvFTD. The most statistically significant differences in protein levels were found for VGF, TN-R, NPTXR, TMEM132D, PDYN and NF-M. Patients with FTD were found to have higher levels of TN-R and NF-M, and lower levels of VGF, NPTXR, TMEM132D and PDYN, compared to unaffected individuals. The main findings were reproduced in the independent cohort. In this pilot study, we show a separation of FTD patients from unaffected individuals based on protein levels in CSF. Further investigation is required to explore the CSF profiles in larger cohorts, but the results presented here has the potential to enable future clinical utilization of these potential biomarkers within FTD.


Generation and characterization of monoclonal antibodies against rabbit CD4, CD5 and CD11a antigens.
We describe in this report the production and characterization of monoclonal antibodies (mAb) to the rabbit homologues of CD4, CD5 and CD11a antigens, and their use for phenotypic analysis of rabbit lymphoid cell lines. All the mAbs were produced by immunizing mice with rabbit thymocytes. mAb KEN-4 apparently identified rabbit CD4, precipitated two bands of 42 and 50 kDa under reducing and non-reducing conditions and markedly inhibited allo-MLR. The distribution of antigen-positive cells were restricted to the thymus and classical T-dependent areas in peripheral lymphoid tissues. mAb KEN-5 apparently identified rabbit CD5, precipitated a single polypeptide of 67 kDa similar to other anti-CD5 mAb in the human and mouse. The use of this mAb revealed that CD5+ B cells were infrequent in this species. mAb KEN-11 apparently identified rabbit CD11a and precipitated a heterodimer of 150/95 kDa by selectively recognizing the 150 kDa moiety. It blocked cation-dependent aggregation of phorbol ester-induced rabbit Con A blasts and also allo-MLR in a similar manner to other anti-CD11a mAb in various animal species. Phenotypic examination of HTLV-1 transformed rabbit lymphoid cell lines using these mAb clearly indicated that most of them were CD4+, CD5+ and CD11a+, and hence derived from CD4+ T cells. These mAb will be useful tools for the study of the cellular immune system in the rabbit.


Prevalence of obesity and abdominal obesity and their association with metabolic-related conditions in Vietnamese adults: an analysis of Vietnam STEPS survey 2009 and 2015.
The abdominal obesity trends and prevalence are important contributing factors to significant rise of many noncommunicable diseases in Vietnam but have not been well-documented in the literature. This study aimed to describe the prevalence and trends of obesity and abdominal obesity in Vietnam from 2009 to 2015 and evaluate how different definitions of obesity and abdominal obesity are associated with metabolic-related conditions. We conducted a secondary analysis based on the Vietnam STEPS (STEPwise approach to Surveillance) cross-sectional Survey 2009 and 2015. Obesity and abdominal obesity were defined using the body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR) cut-offs from the World Health Organization (WHO) and International Diabetes Federation (IDF). Depending on the specific cut-offs, from 2009 to 2015, obesity prevalence increased from 0.8%-10% to 1.7%-16.4% in women and from 0.8%-10.3% to 1.7%-15% in men; abdominal obesity prevalence increased from 3%-31.3% to 8%-41.7% in women and from 0.3%-19.3% to 0.4%-25% in men. Abdominal obesity using WC-IDF and WHR-WHO definitions had noticeably higher sensitivity and lower specificity for metabolic-related conditions compared to the other four criteria. All anthropometric measurements were statistically correlated with biomarkers/blood pressure in 2009 and 2015 except for fasting glucose. Only WC-IDF and WHR-WHO definitions showed consistent association with all reported metabolic-related conditions regardless of sex and survey years. The prevalence of obesity and abdominal obesity in Vietnam is increasing rapidly, especially abdominal obesity in women regardless of the criteria used. More studies are needed to investigate how using different diagnostic criteria for obesity and abdominal obesity could better identify metabolic-related conditions. Authors received no funding for this study.


Common mechanisms for the control of eukaryotic transcriptional elongation.
Regulation of transcriptional elongation is emerging as an important control mechanism for eukaryotic gene expression. In this essay, we review the basis of the current view of the regulation of elongation in the human c-myc gene and discuss similarities in elongation control among the c-myc, Drosophila hsp70 and the HIV-1 genes. Based upon these similarities, we propose a model for control of expression of these genes at the elongation phase of transcription. This model suggests that distinct promoter elements direct the assembly of RNA polymerase II transcription complexes which differ in their elongation efficiency.


Accelerated ageing of an EAF black slag by carbonation and percolation for long-term behaviour assessment.
The efficient reuse of industrial by-products, such as the electric arc furnace (EAF) black slag, is still hindered by concern over their long-term behaviour in outdoor environments. The aim of this study was to develop an accelerated ageing method to simulate the long-term natural carbonation of EAF slag exposed to the elements. The degree of carbonation achieved in a freshly produced slag after accelerated ageing and in a slag used on a fifteen-year-old unpaved road was very similar. The influence of particle size on accelerated carbonation was assessed, with it being concluded that the slag sample with a particle size bigger than 5-6 mm underwent slight carbonation over time when it was exposed to CO2. The accelerated ageing procedure based on percolating a previously carbonated water solution through the slag column allowed gradual leaching with simulated acid rain, as well as providing information about the gradual and total chemical release from the slag. Three classification groups were established according to the release rate of the determined elements. The joint use of the accelerated carbonation method and the percolation test is proposed as a useful tool for environmental risk assessment concerning the long-term air exposure of EAF black slag.


T cell recognition of beryllium.
Chronic beryllium disease (CBD) is a granulomatous lung disorder caused by a hypersensitivity to beryllium and characterized by the accumulation of beryllium-specific CD4(+) T cells in the lung. Genetic susceptibility to beryllium-induced disease is strongly associated with HLA-DP alleles possessing a glutamic acid at the 69th position of the β-chain (βGlu69). The structure of HLA-DP2, the most prevalent βGlu69-containing molecule, revealed a unique solvent-exposed acidic pocket that includes βGlu69 and represents the putative beryllium-binding site. The delineation of mimotopes and endogenous self-peptides that complete the αβTCR ligand for beryllium-specific CD4(+) T cells suggests a unique role of these peptides in metal ion coordination and the generation of altered self-peptides, blurring the distinction between hypersensitivity and autoimmunity.


Optimization of the use of ciprofloxacin.
To compare mutant prevention concentration (MPC) of ciprofloxacin and time-killing curve with regards to 11 genotyped Escherichia coli. MICs were determined using the E-test method. Time-killing studies were performed in accordance with the NCCLS guidelines. The genes gyrA, gyrB, parC, parE and marR were amplified by PCR and sequenced. The MPC was defined as the lowest antibiotic concentration preventing the growth of resistant colonies when 10(10) CFU/mL were spread on a solid medium. Strains with no genes gyrA, gyrB, parC, parE and marR mutation presented MIC less or equal to 0.023 mg/L and MPC less or equal to 0.25 mg/L. Strains with two mutations (gyrA and parC) presented MIC equal to 1.5 mg/L and MPC equal to 4 mg/L. Strains with one mutation (gyrA) presented MIC less or equal to 0.75 mg/L, but MPC ranged from 0.5 to 6 mg/L depending of the MIC of ciprofloxacin. The time-killing curves for ciprofloxacin showed a bactericidal activity of 0.25 mg/L in 1h for strains without mutation, compared with a bactericidal activity of 2 and 4 mg/L in 4h for strains with one and two mutations, respectively. For strains of E. coli resistant to nalidixic acid, it was necessary to evaluate the MIC of ciprofloxacin in order to asses the optimal dosage of ciprofloxacin.


Automated static perimetry as a screening method for evaluation of retinal perfusion in diabetic retinopathy.
The aim of our study was firstly to assess whether areas of capillary non-perfusion in diabetic retinopathy are associated with reduction of retinal light sensitivity and secondly to assess whether automated perimetry can serve as a screening method for evaluation of retinal perfusion. 32 eyes with diabetic retinopathy and 30 eyes of controls underwent visual field testing on the 30-2 program of the Humphrey field analyser and fluorescein angiography. The results are compared with the 'superimposition technique'. In 93.4% of our diabetic eyes (30 from 32) areas of capillary non-perfusion demonstrated by fluorescein angiography were associated with areas of reduced retinal sensitivity. The correlation between visual field defects and areas of reduced retinal perfusion was significant with probability more than 99% (P<0.01). In view of our findings we recommend automated static perimetry as a very sensitive method for evaluation of retinal perfusion in diabetic patients.


Upper gastrointestinal bleeding due to duodenum diverticulum: a challenge for the endoscopist.
An 80-year-old female with a mechanic mitral valve treated with acenocumarol was admitted to the hospital due to tarry stools over the last two days and hemoglobin levels of 5.6 g/dl. She had not biliary pathology. An emergency esophagogastroduodenoscopy showed lots of fresh clots over the second part of the duodenum that seemed to come from the major papilla. A duodenoscopy was performed in order to obtain a direct view, showing a huge clot near the papilla. Its removal with a polypectomy snare revealed a large duodenum diverticulum with little saculations inside, one of which showed a visible, actively bleeding vessel. Sclerosis with epinephrine was performed and subsequently, two through-the-scope Cook® 11 mm clips were placed, achieving the cessation of the hemorrhage. Several attempts with different clips were needed since they were separated by the elevator nail of the duodenoscope. No complications developed during the procedure or once anticoagulation was restarted.


[Alimentary nickel and contact eczema (author's transl)].
By atomic absorption spectrometry, nickel was analysed in many foodstuffs. The results of these determinations are given in detail. Nickel present in vegetables comes primarily from the soil but secondarily from stainless-steel cooking utensils.


The effect of late pregnancy date fruit consumption on delivery progress - A meta-analysis.
To summarize the available evidence exploring the influence of date fruit consumption on delivery outcomes. A search was conducted for relevant articles in three databases for manuscripts in English, with no time restrictions. Four articles were eligible for inclusion. Women consuming date fruit were admitted with higher cervical dilatation (mean difference (MD) 1.1 cm [95% confidence interval (CI) 0.2-1.99 cm) and yielded a lower need for labor induction/augmentation (relative risk (RR) 0.6, 95% CI 0.43-0.83). Date fruit consumption was associated with shorter latent phase (MD -4.6 hours, 95% CI -7.77 to -1.4) and second stage duration (MD -7.7 minutes, 95% CI -12.0 to -3.4). Although the overall quality of the included studies was weak due to high risk of bias, the results of our meta-analysis point to beneficial effects of date fruit consumption on labor process. fruit.


Acoustic signal typing for evaluation of voice quality in tracheoesophageal speech.
Because of the aperiodicity of many tracheoesophageal voices, acoustic analysis of the tracheoesophageal voice is less straightforward than that of the normal voice. This study presents the development and testing of an acoustic signal typing system based on visual inspection of a narrow-band spectrogram that can be used by researchers for classification of voice quality in tracheoesophageal speech. In addition to this classification system, a selection of acoustic measures [median fundamental frequency, standard deviation of fundamental frequency, jitter, percentage of voiced (%Voiced), harmonics-to-noise ratio (HNR), glottal-to-noise excitation (GNE) ratio, and band energy difference (BED)] was computed to provide more insight into the acoustic components of tracheoesophageal voice quality. For clinical relevance, relationships between the acoustic signal types and an overall judgment of the voice were investigated as well. Results showed that the four acoustic signal types form a good basis for performing more acoustic analyses and give a good impression of the overall quality of the voice.


Comprehensive multidimensional separations for the analysis of petroleum.
Petroleum analysis presents many unique challenges as a result of the overwhelming number of compounds present in petroleum samples. Consequently the use of multidimensional separation techniques will almost invariably be required in order to overcome these challenges. Within this paper we review recent developments in the application of comprehensive multidimensional techniques for petroleum analysis focusing on more recent applications. Basic instrumentation for various comprehensive multidimensional techniques is outlined along with an overview of a broad range of applications in both group-type and target molecule analyses for petroleum and biofuel analysis. In addition, strategies for data interpretation and chemometric analysis of multidimensional data are also reviewed.


HELLP syndrome: an atypical presentation.
HELLP syndrome without proteinuria or hypertension is rare. We present the case of a 33-year-old primigravid who initially was diagnosed with pulmonary embolism. The patient was readmitted with a diagnosis of subcapsular hematoma and eventually diagnosed with HELLP syndrome with a sequela of hepatic rupture.


A factor confirmation and convergent validity of the "areas of worklife scale" (AWS) to Spanish translation.
Perceived incongruity between the individual and the job on work-life areas such as workload, control, reward, fairness, community and values have implications for the dimensions of burnout syndrome. The "Areas of Work-life Scale" (AWS) is a practical instrument to measure employees´ perceptions of their work environments. Validate a Spanish translation of the AWS, and it relationship with Masclach Burnout Inventory dimensions. The study was conducted in three medium-sized hospitals and seven rural and urban Primary Care centres (N = 871) in Spain. The "Maslach Burnout Inventory General Survey" (MBI-GS) and AWS were applied. We developed a complete psychometric analysis of its reliability, and validity. Data on the reliability supported a good internal consistency (Cronbach α between .71, and .85). Construct validity was confirmed by a six factor model of the AWS as a good measure of work environments (χ²(₃₅₂) = 806.21, p < 0.001; χ²/df = 2.29; CFI = 0.935, RMSEA = 0.039); concurrent validity was analysed for its relationship with other measures (opposing dimensions to burnout, and MBI), and each correlation between dimensions and sub-dimensions were statistically significant; as well, predictive validity, by a series of Multiple Regression Analysis examined the resulting patterns of the Confirmatory Factor Analysis (CFA) confirms the relationship between the work-life areas and burnout dimensions. Leiter and Maslach's AWS has been an important instrument in exploring several work-life factors that contribute to burnout. This scale can now be used to assess the quality of work-life in order to design and assess the need for intervention programs in Spanish-speaking countries.


Reflexions on some aspects of the interactions among ROS, RNS, and Ca(2+) in response to a mycorrhizal or a pathogenic fungus.
In vivo redox activities in the apoplast of axenically cultured intact seedling roots (superoxide anion generation, and superoxide dismutase and peroxidase activities) in contact with the compatible arbuscular mycorrhizal fungus (AMF) were clearly attenuated in comparison with those in contact with the pathogenic fungus (PF) or treated with MeJA, even at the early stages of treatment. Contact of roots with the AMF did not enhance the biosynthesis of phenolic compounds (total phenolics, flavonoids, and phenylpropanoid glycosides), while contact with the PF significantly enhanced the biosynthesis of all phenolic fractions. Reactive oxygen and nitrogen species both seemed to be involved in these responses from the first moments of contact, but the fluorescence imaging of roots showed that ROS were mainly accumulated in the apoplast while NO was mainly stored in the cytosol. In conclusion, intact olive seedling roots clearly differentiated between AMF and PF.