Sissies, Mama's Boys, and Tomboys: Is Children's Gender Nonconformity More Acceptable When Nonconforming Traits Are Positive?
The evaluation of gender nonconformity in children was examined in two studies. In Study 1, 48 young adults evaluated the positivity of culturally popular labels for gender nonconformity, including "tomboy," "sissy," and two new labels generated in a pilot study, "mama's boy" and "brat." The "mama's boy" was described as a boy who has positive feminine traits (gentle and well-mannered) as opposed to the "sissy" who was described as having negative feminine traits (crying and easily frightened). In Study 2, 161 young adults read descriptions of gender-typical and nonconforming children, evaluating them in several domains. The label "mama's boy" was considered negative in Study 1 but an unlabeled positive nonconforming boy was rated as likable and competent in Study 2. However, participants worried about nonconforming boys, saying they would encourage them to behave differently and describing such children with derogatory sexual orientation slurs. "Tomboy" was generally considered a positive label in Study 1. In Study 2, gender nonconforming girls were considered neither likable nor dislikeable, and neither competent nor incompetent, reflecting ambivalence about girls' nonconformity. It may be that we use gender nonconformity labels as indicators of sexual orientation, even in young children. Therefore, even when an individual displays objectively positive traits, the stigma associated with homosexuality taints judgments about their nonconforming behavior.


The regulation of mesodermal progenitor cell commitment to somitogenesis subdivides the zebrafish body musculature into distinct domains.
The vertebrate musculature is produced from a visually uniform population of mesodermal progenitor cells (MPCs) that progressively bud off somites populating the trunk and tail. How the MPCs are regulated to continuously release cells into the presomitic mesoderm throughout somitogenesis is not understood. Using a genetic approach to study the MPCs, we show that a subset of MPCs are set aside very early in zebrafish development, and programmed to cell-autonomously enter the tail domain beginning with the 16th somite. Moreover, we show that the trunk is subdivided into two domains, and that entry into the anterior trunk, posterior trunk, and tail is regulated by interactions between the Nodal and bone morphogenetic protein (Bmp) pathways. Finally, we show that the tail MPCs are held in a state we previously called the Maturation Zone as they wait for the signal to begin entering somitogenesis.


Monocytes and macrophages in malignant melanoma. III. Reduction of nitroblue tetrazolium by peripheral blood monocytes.
Peripheral-blood monocytes from normal individuals and from patients with malignant melanoma reduce nitroblue tetrazolium (NBT). A quantitative assay for dye reduction was applied to 25 healthy donors and 31 patients with malignant melanoma. NBT reduction expressed as dye reduction per monocyte was significantly impaired in patients with disseminated disease, and they responded poorly to a phagocytic stimulus. Monocytes from patients with micrometastatic disease, however, showed normal resting NBT reduction but, following exposure to a suspension of latex-polystyrene, showed significantly greater NBT reduction than those from normal individuals. Since NBT reduction is an indirect measure of intracellular hexose-monophosphate-shunt activity we conclude that the monocytes from patients with minimal disease are in some way activated.


Synthesis and characterization of bis[N'-(4-carboxybenzylidene)]-pyridine-2,6-dicarbohydrazide: colorimetric and fluorometric modulation in presence of F- ions.
A novel organic compound bis[N'-(4-carboxybenzylidene)]-pyridine-2,6-dicarbohydrazide (L) was synthesized and characterized using spectroscopic and X-ray diffraction techniques. Tetrabutyl ammonium halides [(Bu)4N(+)X(-)] X = F, Cl, Br and I were allowed to react separately with a solution of L in DMSO (1 × 10(-5)M). The solution of L turned to shining yellow colour in the presence of F(-) ion only. The binding properties have been studied using absorption, emission and (1)H NMR titrations. Theoretical studies on compound L and compound L+X(-) (X = F, Cl and Br) in DMSO medium were carried out using density functional theory (DFT) at the B3LYP/6-31 G(d,p)/6-31 G+(d,p) level. The theoretical calculations agreed to the experimental results.


Beta RBD boost broadens antibody-mediated protection against SARS-CoV-2 variants in animal models.
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) with resistance to neutralizing antibodies are threatening to undermine vaccine efficacy. Vaccination and infection have led to widespread humoral immunity against the pandemic founder (Wu-Hu-1). Against this background, it is critical to assess the outcomes of subsequent immunization with variant antigens. It is not yet clear whether heterotypic boosts would be compromised by original antigenic sin, where pre-existing responses to a prior variant dampen responses to a new one, or whether the memory B cell repertoire would bridge the gap between Wu-Hu-1 and VOCs. We show, in macaques immunized with Wu-Hu-1 spike, that a single dose of adjuvanted beta variant receptor binding domain (RBD) protein broadens neutralizing antibody responses to heterologous VOCs. Passive transfer of plasma sampled after Wu-Hu-1 spike immunization only partially protects K18-hACE2 mice from lethal challenge with a beta variant isolate, whereas plasma sampled following heterotypic RBD boost protects completely against disease.


Release of arachidonic acid metabolites by human fetal membranes: interrelationship between leukotriene B4 and prostaglandin E2.
The objective of this study was to ascertain whether human fetal membranes metabolize arachidonic acid preferentially through the lipoxygenase rather than the cyclooxygenase pathway before labor and whether an interaction between lipoxygenase and cyclooxygenase products is present in these tissues. Reflected fetal membranes were obtained from 8 healthy women at term gestation who were delivered by elective repeat cesarean section before the onset of labor. Tissues were cultured either in the presence or in the absence of the calcium ionophore A23187 for 60 minutes. Leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) were measured in culture medium by radioimmunoassays. Moreover, the effect of different concentrations of exogenously added LTB4 on PGE2 release was evaluated. The basal and stimulated output of LTB4 by tissues was significantly higher than that of PGE2. Addition of LTB4 significantly decreased PGE2 release by tissues. These findings suggest that in the above tissues: 1) the arachidonate lipoxygenase pathway is highly active before labor; 2) LTB4 might play a role in the regulation of PGE2 production.


Fungal and plant gene expression during the colonization of cacao seedlings by endophytic isolates of four Trichoderma species.
Endophytic isolates of Trichoderma species are being considered as biocontrol agents for diseases of Theobroma cacao (cacao). Gene expression was studied during the interaction between cacao seedlings and four endophytic Trichoderma isolates, T. ovalisporum-DIS 70a, T. hamatum-DIS 219b, T. harzianum-DIS 219f, and Trichoderma sp.-DIS 172ai. Isolates DIS 70a, DIS 219b, and DIS 219f were mycoparasitic on the pathogen Moniliophthora roreri, and DIS 172ai produced metabolites that inhibited growth of M. roreri in culture. ESTs (116) responsive to endophytic colonization of cacao were identified using differential display and their expression analyzed using macroarrays. Nineteen cacao ESTs and 17 Trichoderma ESTs were chosen for real-time quantitative PCR analysis. Seven cacao ESTs were induced during colonization by the Trichoderma isolates. These included putative genes for ornithine decarboxylase (P1), GST-like proteins (P4), zinc finger protein (P13), wound-induced protein (P26), EF-calcium-binding protein (P29), carbohydrate oxidase (P59), and an unknown protein (U4). Two plant ESTs, extensin-like protein (P12) and major intrinsic protein (P31), were repressed due to colonization. The plant gene expression profile was dependent on the Trichoderma isolate colonizing the cacao seedling. The fungal ESTs induced in colonized cacao seedlings also varied with the Trichoderma isolate used. The most highly induced fungal ESTs were putative glucosyl hydrolase family 2 (F3), glucosyl hydrolase family 7 (F7), serine protease (F11), and alcohol oxidase (F19). The pattern of altered gene expression suggests a complex system of genetic cross talk occurs between the cacao tree and Trichoderma isolates during the establishment of the endophytic association.


Draft Genome Sequence of Geobacillus kaustophilus GBlys, a Lysogenic Strain with Bacteriophage OH2.
Geobacillus kaustophilus strain GBlys was isolated along with the bacteriophage OH2, which infects G. kaustophilus NBRC 102445(T). Here we present a draft sequence of this strain's genome, which consists of 216 contigs for a total of 3,541,481 bp, 3,679 predicted coding sequences, and a G+C content of 52.1%.


Aplisulfamines, new sulfoxide-containing metabolites from an aplidium tunicate: absolute stereochemistry at chiral sulfur and carbon atoms assigned through an original combination of spectroscopic and computational methods.
Two new sulfoxide-containing metabolites, aplisulfamines A and B, have been isolated from an Aplidium sp. collected in the Bay of Naples. Their planar structure and geometry of a double bond were readily determined by using standard methods, mainly NMR spectroscopy. An original approach was used to assign the absolute configuration at the three contiguous chiral centers present in the structures of both aplisulfamines, two at carbon and one at sulfur. This involved Electronic Circular Dichroism (ECD) studies, J-based configuration analysis and Density Functional Theory (DFT) calculations and represents an interesting integration of modern techniques in stereoanalysis, which could contribute to the enhancement of theoretical protocols recently applied to solve stereochemical aspects in structure elucidation.


Clinical outcomes of patients with a high alpha-fetoprotein level but without evident recurrence on CT or MRI in surveillance after curative-intent treatment for hepatocellular carcinoma.
Multiphasic CT or MRI and serum alpha-fetoprotein (AFP) are widely used for posttreatment surveillance of hepatocellular carcinoma (HCC). This study aimed to investigate the clinical outcomes of patients with high posttreatment AFP but without evident recurrence on CT or MRI after curative-intent treatment of HCC. We retrospectively analyzed 121 patients presenting with high posttreatment AFP (> 20 ng/mL) without evident recurrence on multiphasic CT or MRI during surveillance after curative-intent surgical resection or radiofrequency ablation (RFA) for HCC. The time interval from the first event of high posttreatment AFP to imaging-evident recurrence (TimeAFP-Imaging recurrence) was estimated using the Kaplan-Meier method. Cox regression analyses were performed to assess the associated factors with TimeAFP-Imaging recurrence. The median TimeAFP-Imaging recurrence was 20.0 months (95% CI 13.0-28.0 months), and the estimated 6-month and 1-year cumulative incidences of imaging-evident recurrence were 24.4% and 40.1%, respectively. In multivariate Cox analyses, late onset of AFP elevation (> 3 months after treatment) was an independent predictor of shorter TimeAFP-Imaging recurrence (HR 2.11, P = 0.015) if using variables available at the first event of AFP elevation, while non-normalization of AFP at the next follow-up was an independent predictor of shorter TimeAFP-Imaging recurrence (HR 3.65, P < 0.001) if using variables including the follow-up data. In the surveillance setting after curative-intent treatment of HCC, patients presenting with high posttreatment AFP without evident recurrence on CT or MRI may frequently progress to imaging-evident recurrence. In high-risk patients, an extensive diagnostic workup or close monitoring is needed to detect HCC recurrence earlier.


Identifying the potential sources of di-(2-ethylhexyl) phthalate contamination in the sediment of the Houjing River in southern Taiwan.
Sediment samples were analyzed for di-(2-ethylhexyl) phthalate (DEHP), an organic endocrine disruptor, in Houjing River in southern Taiwan. The average DEHP concentration at 10 sampling locations, spanning from upper, middle, and lower segments of the stream, was calculated at 3.81+/-6.36mgkg(-1)drywt. Highest concentration was recorded at the Jhongsing Bridge (20.22mgkg(-1)drywt.) near the Dashe Industrial Park, followed by the Renwu Bridge (8.93mgkg(-1)drywt.) near the Renwu Industrial Park. The surface sediment concentration of DEHP was found to be higher in the dry season (October and December), and lower in the wet (flood) season (August), indicating that sources of DEHP remained active and continued to recharge the Houjing River. Vertical sediment core analysis revealed that highest concentration occurred at the depth of 40-60cm, indicating that historical discharges of DEPH may have been higher than recent years. Domestic comparison of DEHP concentrations in sediment from highest to lowest could be categorized as northern, southern, central, and eastern Taiwan, respectively, and seemed to be positively correlated with population density and/or industrial activity. Compared to other countries, DEHP concentration of the Houjing River was relatively higher than rivers studied in Japan, Germany, Italy, and Malaysia, and was relatively lower than the Aire and Trent Rivers in the United Kingdom.


Learning from lived experience: Outcomes associated with students' involvement in co-designed and co-delivered recovery-oriented practice workshops.
Learning from individuals with lived experience is considered an important element of developing recovery-oriented practice capabilities in mental health contexts. Additionally, service user involvement in the education of occupational therapy students is a requirement in accreditation standards. Despite this, many barriers to meaningful inclusion of Lived Experience Educators have previously been identified. This study evaluated the outcomes achieved by students who were involved in a unit of study that incorporated four recovery-oriented practice workshops that were co-designed and co-delivered by Lived Experience Educators and an occupational therapy academic. Change over time was measured using the Recovery Knowledge Inventory (RKI) and the Capabilities for Recovery Oriented Practice Questionnaire (CROP-Q). Change over time was evaluated using paired t-tests. Students also provided qualitative feedback at the conclusion of the workshops. These comments were analysed using interpretive content analysis. Students' scores on the RKI and CROP-Q both demonstrated statistically significant improvements from the beginning of the semester to the end of semester (RKI: 53.6-57.7, t = 6.3, P < 0.001; CROP-Q: 75.6-77.0, t = 2.4, P = 0.019). The most common categories included in the qualitative comments were: "Learning from real experiences"; "Learning about how to be a better clinician"; "See the strength and resilience of the educators, reduce stigma"; "Learning about the negative aspects of the mental health system"; and "More effective than other types of learning". This study has demonstrated that students who engaged with the co-designed and co-delivered workshops improved their recovery knowledge and recovery-oriented capabilities over the course of the semester. Qualitative feedback also suggests that students' attitudes and skills for future practice were also influenced in positive ways by engaging with Lived Experience Educators.


Functional localization of the auditory thalamus in individual human subjects.
Here we describe an easily implemented protocol based on sparse MR acquisition and a scrambled 'music' auditory stimulus that allows for reliable measurement of functional activity within the medial geniculate body (MGB, the primary auditory thalamic nucleus) in individual subjects. We find that our method is equally accurate and reliable as previously developed structural methods, and offers significantly more accuracy in identifying the MGB than group based methods. We also find that lateralization and binaural summation within the MGB resemble those found in the auditory cortex.


Evaluation of different DNA extraction methods based on steel-bullet beating for molecular diagnosis of onychomycosis.
Considering increased trends toward molecular methods for detection/identification of fungi causing onychomycosis, the aim of this study is comparison three DNA extraction methods based on steel-bullet beating to extract DNA from nail. Ex -vivo onychomycosis model was developed using bovine hoof with Candida albicans and Aspergillus flavus. For two models, total DNA was extracted using the three different methods. In method 1, the extraction and purification were performed by steel-bullet beating and phenol chloroform protocol, respectively. In method 2, a freezing step were applied before beating. The purification step in method 3 was carried out using a commercial kit, although DNA extraction was done similarly to method 1 in that approach. To evaluate the efficacy of each method, the extracted genomic DNA was amplified with Polymerase Chain Reaction (PCR) using Internal Transcribed Spacer (ITS) regions. Moreover, 50 nail samples were evaluated for onychomycosis using direct microscopy examination as well as PCR in order to evaluate the diagnostic efficiency of the optimal DNA extraction method. Regarding the desirable quality of the extracted DNA, cost effectiveness, and simplicity, method 1 could be used to extract DNA effectively. Additionally, the obtained data showed that PCR had a higher detection rate of fungal agents in the nail samples than direct microscopic examination. This study demonstrated that the mechanical disruption of the cell wall by steel-bullet beating is a useful and practical method to improve the quantity and quality of fungal DNA thorough the extraction process.


The long-term safety and tolerability of high-dose interferon beta-1a in relapsing-remitting multiple sclerosis: 4-year data from the PRISMS study.
In the prevention of relapses and disability by interferon subcutaneously in multiple sclerosis (PRISMS) study, 560 patients with relapsing-remitting multiple sclerosis were randomized to receive subcutaneous interferon (IFN) beta-1a, 22 or 44 mug three times weekly, or placebo, for 2 years. Patients receiving placebo were then re-randomized to one of the two doses of IFN beta-1a for a further 2 years, whilst patients receiving active treatment continued their original treatment. Safety assessments were performed throughout the study. The most common adverse events for patients originally randomized to active treatment were injection-site inflammation (72% of patients had at least one event), headache (71%) and influenza-like symptoms (69%). These were generally mild in nature and most frequent during the first month of treatment. The 4-year adverse event profiles for the two IFN beta-1a doses were comparable with those observed during the initial phase of the study and, for the most part, with each other. There was no association between IFN beta-1a and depression or suicide/attempted suicide. The most common laboratory abnormalities were asymptomatic lymphopenia and elevated serum liver transaminase levels. These were generally mild and resolved spontaneously. Therapy with subcutaneous IFN beta-1a three times weekly for up to 4 years was well tolerated without dose-limiting safety concerns.


Sjögren's syndrome in children with recurrent parotitis.
Optimize the diagnosis of pediatric Sjögren's syndrome in children who present with parotitis. Twenty children presented to a pediatric otolaryngology or rheumatology clinic with recurrent parotitis. Presenting symptoms, serologies, sialendoscopy findings, and minor salivary gland biopsy pathology results were reviewed. Twenty patients aged 3-17 years presented with recurrent parotitis. Ten percent of this cohort met the American-European Consensus Group adult diagnostic criteria for Sjögren's syndrome. Forty percent of this cohort met diagnosis of Sjögren's syndrome when utilizing Bartunkova's proposed pediatric criteria for diagnosis of Sjögren's syndrome. Sjögren's syndrome is surprisingly common in pediatric patients who present with recurrent parotitis. Otolaryngologists who treat pediatric parotitis should have a high index of suspicion for Sjögren's syndrome. 4.


Cationic isotachophoresis separation of the biomarker cardiac troponin I from a high-abundance contaminant, serum albumin.
Cationic ITP was used to separate and concentrate fluorescently tagged cardiac troponin I (cTnI) from two proteins with similar isoelectric properties in a PMMA straight-channel microfluidic chip. In an initial set of experiments, cTnI was effectively separated from R-Phycoerythrin using cationic ITP in a pH 8 buffer system. Then, a second set of experiments was conducted in which cTnI was separated from a serum contaminant, albumin. Each experiment took ∼10 min or less at low electric field strengths (34 V/cm) and demonstrated that cationic ITP could be used as an on-chip removal technique to isolate cTnI from albumin. In addition to the experimental work, a 1D numerical simulation of our cationic ITP experiments has been included to qualitatively validate experimental observations.


Vaccination with metastasis-related tumor associated antigen TPD52 and CpG/ODN induces protective tumor immunity.
Tumor protein D52 (TPD52) is involved in transformation and metastasis and has been shown to be over-expressed in tumor cells compared to normal cells and tissues. Murine TPD52 (mD52) shares 86% protein identity with the human TPD52 orthologue (hD52). To study TPD52 protein as a target for active vaccination recombinant, mD52 was administered as a protein-based vaccine. Naïve mice were immunized with either mD52 protein and CpG/ODN as a molecular adjuvant or CpG/ODN alone. Two weeks following the final immunization, mice were challenged s.c. with syngeneic tumor cells that over-express mD52. Two distinct murine tumor cell lines were used for challenge in this model, mKSA and 3T3.mD52. Half of the mice immunized with mD52 and CpG/ODN rejected or delayed onset of mKSA s.c. tumor cell growth, and 40% of mice challenged with 3T3.mD52 rejected s.c. tumor growth, as well as the formation of spontaneous lethal lung metastases. Mice immunized with mD52 and CpG/ODN generated detectable mD52-specific IgG antibody responses indicating that mD52 protein vaccination induced an adaptive immune response. In addition, mice that rejected tumor challenge generated tumor-specific cytotoxic T lymphocytes' responses. Importantly, microscopic and gross evaluation of organs from mD52 immunized mice revealed no evidence of autoimmunity as assessed by absence of T cell infiltration and absence of microscopic pathology. Together, these data demonstrate that mD52 vaccination induces an immune response that is capable of rejecting tumors that over-express mD52 without the induction of harmful autoimmunity.


Mismatch-specific post-meiotic segregation frequency in yeast suggests a heteroduplex recombination intermediate.
Post-meiotic segregation of alleles, which is seen, for example, in the 5:3 distribution of alleles in the products of a single meiosis in fungi, has been thought to be due to the non-repair of heteroduplex regions formed during genetic recombination. In current models of genetic recombination, heteroduplex DNA is formed either as the primary intermediate generated by two interacting non-sister chromatids or as a short region flanking a double-stranded gap. The frequency of post-meiotic segregation differs for different alleles, and this is presumed to reflect the varying efficiencies with which different types of mismatches in the heteroduplex are repaired. To gain some insight into this process, we have now determined the nucleotide sequences of various yeast alleles with different post-meiotic segregation frequencies and compared the mismatches predicted to occur in heteroduplexes of these alleles with wild-type DNA with those repaired with varying efficiency in bacterial systems. A striking correlation is observed, with the mismatches predicted for high post-meiotic segregation frequency alleles being similar to mismatches repaired with low efficiency in bacteria. These results support the view that postmeiotic segregation frequency reflects heteroduplex repair efficiency and the contention that meiotic gene conversion is the result of the successful repair of heteroduplex mismatches.


Analysis of Expert Feedback to Determine Intellectual Standards for Student Pharmacist Clinical Reasoning Development.
Objectives. Clinical reasoning (CR) is one of the most important skills for pharmacy learners. Feedback has been proposed as a pedagogy to improve CR skills; however, essential components of CR have yet to be determined within pharmacy education. This study sought to streamline feedback to align with the Pharmacists' Patient Care Process (PPCP).Methods. The investigators used deidentified clinical reasoning "Keep," "Start," or "Stop" (KSS) feedback comments from student-written CR "think-aloud" sessions with pharmacy students in their third professional year. Sections were mapped to the PPCP and were coded by 2 independent investigators according to proposed essential components of CR, using an adapted grounded-theory approach. Investigators could inductively add codes after conferring with the other. Coded feedback was analyzed using a summative content approach. Intercoder reliability was calculated via Holsti index.Results. Five essential components of CR were identified after analysis of 635 KSS comments. The 5 essential components of CR were coded 1178 times. "Accurate," "Concise," "Specific," and "Thorough" were identified a priori, while "Connected" was discovered during feedback comment review. Literature analysis added supporting data to these results through the Paul-Elder Critical Thinking Framework. To maintain consistency in language, these essential components will be referred to as "intellectual standards" moving forward.Conclusion. This novel study successfully identified 5 key intellectual standards of CR. These intellectual standards provide a framework for pharmacy educators to focus feedback to improve student CR. Future research of other intellectual standards pertinent to experiential education is imperative.


Health-related behavior and the use of hormone replacement therapy.
To study health-related differences between hormone replacement therapy (HRT) users and nonusers among colorectal cases and women without diagnosed cancer. Data from the Saskatchewan Health population-based databases were used to ascertain the use of HRT, oral contraceptives (OCs), cardiovascular system (CVS) drugs, central nervous system (CNS) drugs, prescribed NSAIDs and vitamins among 3338 women diagnosed with colorectal cancer and 13025 women without diagnosed cancer. Physician visits and sigmoidoscopy procedures were also determined. Among women without diagnosed cancer, HRT was associated with CVS drugs (OR = 1.23, 95%CI: 1.10-1.37), CNS drugs (OR = 1.96, 95% CI: 1.72-2.23), other hormones (OR = 1.12, 95% CI: 1.01-1.24), prescribed vitamins (OR = 1.37, 95% CI: 1.22-1.55), NSAIDs (OR = 1.41, 95% CI: 1.18-1.68), having had a sigmoidoscopy 3-5 years prior to index dates (OR = 1.33, 95% CI: 1.12-1.59) and 15 or more visits to physicians during the 5th year prior to assigned index date (OR = 2.0, 95% CI: 1.77-2.35). Similar results were observed among women diagnosed with colorectal cancer, but HRT use was not associated with having had a sigmoidoscopy. Health-related characteristics of HRT users and nonusers are identified and described. Some of these factors may contribute to selection bias in studies examining the health benefits of HRT.


Role of cyclic AMP and related enzymes in rat lung growth and development.
Cyclic AMP levels in rat lungs showed phasic elevations which peaked during fetal, neonatal and late postnatal periods of development. Lung phospholipids showed major alterations in their levels during fetal and early neonatal life. Alterations in glycogen levels were accompanied by parallel changes in phosphorylase a/total phosphorylase activity which may be related to changes in cyclic AMP during development. Cyclic AMP levels were dependent on the relative activities of adenylate cyclase and cyclic AMP phosphodiesterase which also changed with age. Activation of adenylate cyclase by norepinephrine and NaF, and of cyclic AMP phosphodiesterase by calcium, was maximum neonatally and declined variably thereafter. These data suggest a relationship between cyclic AMP, glycogen and phospholipids during rat lung development.


A protocol for the Heart Matters stepped wedge cluster randomised trial: The effectiveness of heart attack education in regions at highest-risk.
To describe the Heart Matters (HM) trial which aims to evaluate the effectiveness of a community heart attack education intervention in high-risk areas in Victoria, Australia. These local government areas (LGAs) have high rates of acute coronary syndrome (ACS), out-of-hospital cardiac arrest (OHCA), cardiovascular risk factors, and low rates of emergency medical service (EMS) use for ACS. The trial follows a stepped-wedge cluster randomised design, with eight clusters (high-risk LGAs) randomly assigned to transition from control to intervention every four months. Two pairs of LGAs will transition simultaneously due to their proximity. The intervention consists of a heart attack education program delivered by trained HM Coordinators, with additional support from opportunistic media and a geo-targeted social media campaign. The primary outcome measure is the proportion of residents from the eight LGAs who present to emergency departments by EMS during an ACS event. Secondary outcomes include prehospital delay time, rates of OHCA and heart attack awareness. The primary and secondary outcomes will be analysed at the patient/participant level using mixed-effects logistic regression models. A detailed program evaluation is also being conducted. The trial was registered on August 9, 2021 (NCT04995900). The intervention was implemented between February 2022 and March 2023, and outcome data will be collected from administrative databases, registries, and surveys. Primary trial data is expected to be locked for analysis by October 31st 2023, with a follow-up planned until March 31st 2024. The results from this trial will provide high-level evidence the effectiveness of a community education intervention targeting regions at highest-risk of ACS and low EMS use.


Enhancement of hydralazine hypotension by low doses of isoniazid. Possible role of semicarbazide-sensitive amine oxidase inhibition.
The influence of pretreatment with 1 through 300 mg/kg ip of isoniazid (ISO) on blood pressure and heart rate responses to 0.1 mg/kg iv of hydralazine (HYD) was assessed in rats anesthetized with chloralose--urethane. HYD hypotension was significantly enhanced by ISO at doses between 3 and 300 mg/kg ip. Heart rate was not influenced by HYD in control or pretreated animals. Depressor responses to 0.2 mg/kg iv of pinacidil (PIN) were also potentiated by ISO at 100 and 300, but not at 30 mg/kg. Similarly, ISO decreased cerebral gamma-aminobutyric acid (GABA) at the two highest doses; 30 mg/kg was without effect. Pretreatment of rats with ISO at 1 through 300 mg/kg failed to influence HYD-induced relaxation of aortic rings. These results were interpreted as indicating that potentiation of HYD hypotension by high doses of ISO is not specific for that vasodilator and is related to decreased cerebral GABA, as postulated previously. Lower doses could specifically potentiate the HYD-induced hypotensive effect by inhibition of semicarbazide-sensitive amine oxidase (SSAO), since both ISO and HYD are potent inhibitors of this enzyme. In support of this hypothesis, the SSAO inhibitors, benserazide (100 mg/kg ip) and mexiletine (50 mg/kg ip), were also found to enhance HYD hypotension.


Cardiovascular medication use in patients with undiagnosed obstructive sleep apnoea.
A study was undertaken in patients with undiagnosed sleep apnoea/hypopnoea syndrome (OSAS) to document the use of prescribed medications, especially those used in cardiovascular diseases, in the year before the OSAS diagnosis was confirmed. A total of 549 patients with OSAS (401 men of mean age 47.2 years, mean body mass index (BMI) 35.5 kg/m(2), mean apnoea/hypopnoea index (AHI) 47.2 and148 women of mean age 50.2 years, BMI 39.6 kg/m(2), AHI 32.6) were each matched to one general population control by age, sex, geographical location, and family physician. Medication use was evaluated for patients and controls using a database containing information about all prescriptions completed in the province of Manitoba, Canada. In the year before OSAS was diagnosed, prescribed medication costs were $155.91 (Canadian dollars) (95% CI $91.34 to $220.49) greater for cases than for controls. Cases were dispensed 3.3 (95% CI 1.5 to 5.2) more prescriptions, were on 1.2 (95% CI 0.8 to 1.6) more medications, and were supplied with 157.4 (95% CI 95.9 to 218.8) more daily doses of medication. The odds ratio of OSAS cases being on a prescribed medication was 1.88 relative to controls (95% CI 1.38 to 2.54, p<0.0001). In the same year 36.6% of cases and 19.7% of controls were using medications for cardiovascular disease (OR 2.82, 95% CI 2.05 to 3.89, p<0.0001), consuming 79.4 (95% CI 48.9 to 109.8) more daily doses of medication, having been dispensed 1.7 (95% CI 1.0 to 2.4) more prescriptions, and at a $75.26 (95% CI $44.03 to $106.50) greater cost. The odds ratio of patients with OSAS being on medications indicated for the treatment of systemic hypertension was 2.71 (95% CI 1.96 to 3.77) relative to controls; however, such medications might also be prescribed for other indications such as angina pectoris and congestive heart failure, and for the secondary prevention of myocardial infarction. The use of medications indicated for the treatment of systemic hypertension was predicted significantly by age (odds ratio (OR) 1.10 per year), BMI (OR 1.05 per unit), and AHI (OR 1.01 per unit). In the year before OSAS was diagnosed, patients with OSAS were heavy users of medications, particularly those used to treat cardiovascular diseases.


The effect of polymer length in liquid-liquid phase separation.
Understanding the thermodynamics that drive liquid-liquid phase separation (LLPS) is quite important given the number of diverse biomolecular systems undergoing this phenomenon. Many studies have focused on condensates of long polymers, but very few systems of short-polymer condensates have been observed and studied. Here, we study a short-polymer system of various lengths of poly-adenine RNA and peptides formed by the RGRGG sequence repeats to understand the underlying thermodynamics of LLPS. Using the recently developed COCOMO coarse-grained (CG) model, we predicted condensates for lengths as short as 5-10 residues, which was then confirmed by experiment, making this one of the smallest LLPS systems yet observed. A free-energy model reveals that the length dependence of condensation is driven primarily by entropy of confinement. The simplicity of this system will provide the basis for understanding more biologically realistic systems.


Understanding the physical interactions in the FGF21/FGFR/β-Klotho complex: structural requirements and implications in FGF21 signaling.
The endocrine fibroblast growth factor 21 (FGF21) requires both fibroblast growth factor receptor (FGFR) and β-Klotho for signaling. In this study, we sought to understand the inter-molecular physical interactions in the FGF21/FGFR/β-Klotho complex by deleting key regions in FGFR1c or FGF21. Deletion of the D1 and the D1-D2 linker (the D1/linker region) from FGFR1c led to β-Klotho-independent receptor activation by FGF21, suggesting that there may be a direct interaction between FGF21 and the D1/linker region-deficient FGFR1c. Consistent with this, the extracellular portion of FGFR1c lacking the D1/linker region blocked FGF21 action in a reporter assay, presumably by binding to and sequestering FGF21 from acting on cell surface receptor complex. In addition, the D1/linker region-deficient FGFR1c had enhanced interaction with β-Klotho. Further, we demonstrated that deletion of the D1/linker region enhanced the formation of the FGF21/β-Klotho/FGFR1c ternary complex in both Biacore and asymmetrical flow field flow fractionation studies. Finally, we found that the N-terminus of FGF21 is involved in the interaction with FGFR1c and FGF21/β-Klotho/FGFR1c ternary complex formation. Taken together, our data suggest that the D1/linker region regulates both the FGF21/FGFR1c and FGFR1c/β-Klotho interaction, and a direct interaction of FGF21 with FGFR1c may be an important step in receptor-mediated FGF21 signaling.


Diet shifts in moose due to predator avoidance.
On Isle Royale, Michigan, moose cows which have calves show a different distribution and diet from solitary adults and yearling moose. Solitary adults and yearlings follow a feeding pattern predicted from the location of high nutrient plant growth. In the presence of wolves, they feed on the ridges of the main island, where they take advantage of plants that leaf early; only later in the season do they move to the small outlying islands where plant phenology is delayed by the cold water of Lake Superior. Cows with calves deviate sharply from this pattern. They remain on the wolf-free small islands throughout the growing season. While on the islands, cows with calves eat a poorer quality diet than other moose. They switch to eating high quality spring and summer foods later than other moose and they eat significantly fewer high preference shrubs and significantly more herbs and low preference shrubs than other moose.This study suggests that in order to avoid predators, cows with calves sacrifice the high quality diet available on the main island. These data also suggest that the wolves not only affect prey numbers by direct kills but may also indirectly influence prey numbers by altering the diet of their prey. In this case, the reproductive cows, those individuals that contribute most directly to growth of the population, avoid predators but frequent poor feeding areas.


Poneratoxin, a new toxin from an ant venom, reveals an interconversion between two gating modes of the Na channels in frog skeletal muscle fibres.
The effects of synthetic poneratoxin (PoTX), a new toxin isolated from the venom of the ant Paraponera clavata, were studied under current- and voltage-clamp conditions in frog skeletal muscle fibres. PoTX induces a concentration-dependent (10(-9) M-5 x 10(-6) M) prolongation of the action potentials and, at saturating concentration, a slow repetitive activity developing at negative potentials. PoTX specifically acts on voltage-dependent Na channels by decreasing the peak Na current (INa) and by simultaneously inducing a slow INa which starts to activate at -85 mV and inactivates very slowly. Both the fast and the slow components of INa are suppressed by tetrodotoxin and reverse at the same potential corresponding to the equilibrium potential for Na ions. The fast component of INa has voltage dependence, activation and steady-state inactivation almost similar to those of the control INa. The voltage dependence of the slow Na conductance is 40 mV more negative than that of the fast one. The results suggest that PoTX affects all the Na channels and that the fast and the slow INa components originate from a possible PoTX-induced interconversion between a fast and a slow operating mode of the Na channels.


A gene for familial juvenile nephronophthisis (recessive medullary cystic kidney disease) maps to chromosome 2p.
Familial juvenile nephronophthisis (NPH) is a chronic autosomal recessive kidney disease responsible for 15% of end stage renal failure in children. NPH is frequently (16% of cases) associated with Leber amaurosis (termed Senior-Løken syndrome, SLS). Linkage analyses, performed in 22 multiplex NPH families (18 without and 4 with ocular abnormalities), have localized the gene to a region between D2S48 and D2S51 on chromosome 2p. This was confirmed using adjacent microsatellite markers, one of which (AFM220ze3 at the D2S160 locus) gave a lod score of 4.78 at theta = 0.05 in the 18 families with isolated NPH, whereas the same marker excluded linkage with SLS. These results demonstrate linkage of the purely renal form of NPH to chromosome 2p, and suggest that there may be genetic heterogeneity between NPH and SLS.


The impact of EGFR stimulation and inhibition on BPDE induced DNA fragmentation in oral/oropharyngeal mucosa in vitro.
Still, the vast majority of head and neck squamous cell carcinoma (HNSCC) can be linked to the "traditional" risk factors tobacco smoke and alcohol consumption. These tumors are believed to be the results of multiple years of carcinogenic impact on upper aerodigestive tract mucosa. The frequent observation, that one patient suffers from several synchronous cancers, multiple local recurrences, and second primary tumors led to the concept of field cancerization, first introduced by Slaughter and colleagues in 1953. As underlying molecular events, genetic instability, loss of heterozygosity, amplification, deletion, up- and down-regulation of oncogenes and/or tumor suppressor genes were revealed. One of the best studied oncogenic features of head and neck carcinogenesis are high expression levels of epidermal growth factor receptor (EGFR). Enhanced expression of the receptor was detected in histologically normal mucosa from HNSCC patients and increasing levels during the progress from hyperplasia to dysplastic lesion and invasive carcinoma were demonstrated. Whereas nearly all of our knowledge about EGFR biology in HNSCC is based on preclinical and clinical studies investigating receptor inhibitors, little is known about cause and function of EGFR in premalignant mucosa. In this study we show, that EGFR stimulation significantly decreases carcinogen induced DNA damage in normal mucosa from HNSCC patients and that this effect is completely abrogated adding an anti-EGFR antibody before stimulation, while there was no effect in non-tumor controls. The effect of EGFR inhibition was contrary. In non-tumor controls, blocking the receptor with an antibody significantly decreased DNA damage, whereas in cases no effect was seen. Our results indicate an important role of the receptor during chemical carcinogenesis. On the basis of this study we suppose, that increasing EGFR levels during head and neck carcinogenesis can be interpreted as a physiological response to permanent carcinogen impact on the mucosa.


[Detection of total and covalently closed circular HBV DNA in liver transplant recipients due to HBV-associated liver diseases].
To investigate the levels of hepatitis B virus (HBV) total DNA and covalently closed circular (ccc) DNA in liver transplant recipients due to HBV-associated liver diseases and detemaine their clinical significance. Sixty patients undergoing liver transplantation (LT) due to HBV-associated liver diseases were enrolled for the study. Levels of HBV total and ccc DNA in plasma, liver and PBMCs were measured by RT-PCR. The ratio of male:female participants was 48:12. The mean age was 52.98+/-9.40 years old, and the median duration post-LT was 72 (25-128) months. 59 of the patients had no detectable HBV DNA in plasma.Four patients had detectable levels of total HBV DNA in PBMCs, but no detectable ccc DNA. Five patients had detectable levels of total HBV DNA in liver, and two of those also had detectable levels of ccc DNA. One patients who had detectable HBV DNA in PBMCs suffered HBV recurrence. The liver transplant recipients with detectable levels of HBV total and ccc DNA in PBMCs and liver should be considered high risk for HBV recurrence following LT.


Crystal structure of methyl 3-amino-2,3-dideoxy-beta-D-arabino-hexopyranoside. Stabilization of the crystal lattice by a double network of N-H...O, O-H...N and O-H...O interactions.
The structure, conformation and configuration of methyl 3-amino-2,3-dideoxy-beta-D-arabino-hexopyranoside were investigated by (1)H NMR, (13)C NMR and IR spectroscopy, as well as by optical rotation. The crystal structure was confirmed by single-crystal X-ray crystallographic analysis at 293 K and R = 0.0434 based on 910 independent reflections. The crystal belongs to the monoclinic system, space group of P2(1) with cell dimensions a = 6.050(1) Angstroms, b = 7.284(1) Angstroms, c = 10.289(2) Angstroms, beta = 104.69(3) degrees, D(c) = 1.341 Mg cm(-3) and V = 438.9(1) Angstroms(3) for Z = 2. Furthermore, the molecule has a typical (4)C(1) chair conformation. Hydrogen bonds between sugar molecules are responsible for stabilizing the crystal lattice.


Timing of initiation of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis.
The aim of the study is to summarize the effects of timing of initiation of renal replacement therapy (RRT) on mortality. A systematic search for randomized controlled trials (RCTs) and other clinical studies was performed without language restriction in PubMed, Web of Science, and Embase. We estimated pooled relative risk ratios (RRs) and 95% confidence intervals (CIs) using fixed effects model or random effects model as appropriate. Heterogeneity, publication bias, and subgroup analyses were conducted. We analyzed the date extracted from 15 studies (3 RCTs, 2 prospective, and 10 retrospective comparative cohort studies) with a total of 2955 patients. Overall, 51.0% (772/1514) patients died in the "early" RRT group compared with 58.0% (836/1441) in the "late" RRT group. The pooled RR was 0.71 (95% CI: 0.59, 0.86), but the heterogeneity existed (p < 0.00001). Subgroup analysis based on modality did not record heterogeneity across trials. In continuous RRT (CRRT) group (n = 607), patients treated with "early" CRRT suggested a significant decrease in mortality compared with those in "late" CRRT group (27.8% vs. 43.0%) and the RR was 0.69 (95% CI: 0.56, 0.84) without evidence of heterogeneity (I2 = 33%, p = 0.18). In intermittent hemodialysis (IHD) group (n = 115), the RR was 0.26 (95% CI: 0.15, 0.45) without evidence of heterogeneity (I2 = 0%, p = 0.50). In the mixed group, heterogeneity existed. "Early" CRRT and "early" IHD both could reduce the mortality of patients with acute kidney injury compared with "late" CRRT or IHD.


Single-step purification and h.p.l.c. analysis of glutathione transferase 8-8 in rat tissues.
GSSG selectively elutes two GSH transferases from a mixture of rat GSH transferases bound to a GSH-agarose affinity matrix. One is a form of GSH transferase 1-1 and the other is shown to be GSH transferase 8-8. By using tissues that lack this form of GSH transferase 1-1 (e.g. lung), GSH transferase 8-8 may thus be purified from cytosol in a single step. Quantitative analysis of the tissue distribution of GSH transferase 8-8 was obtained by h.p.l.c.


Adapted Tango Improves Mobility, Motor-Cognitive Function, and Gait but Not Cognition in Older Adults in Independent Living.
To determine the efficacy of adapted tango for improving mobility, motor-cognitive function, and gait; to determine whether former dance experience was associated with improvements; and to evaluate participant satisfaction, changes in depression, and quality of life. Quasi-experimental, two-group, repeated-measures preintervention, postintervention, and 3-month postintervention study. Diverse senior independent living communities in an urban metropolitan area. Individuals aged 59 to 95 (73% aged 80 and older; 31% nonwhite, 72% female) (N = 74). Participants were assigned to 20 sessions of 90-minute tango (n = 62) or health education (n = 12) classes over 12 weeks. Mobility, motor-cognitive function, gait, cognition, and psychosocial function were evaluated before, immediately after, and 3 months after the intervention. Two (groups) by two (before and after) repeated-measures analyses of variance with post hoc comparisons were used to evaluate differences in primary analyses. Secondary analyses from immediately after to 3 months after were used to examine the data for retention of any gains. Forty-four tango and 10 education participants completed 20 sessions. Significant group by time interactions revealed that tango improved mobility (P = .006), backward and fast gait speeds (P < .001), and motor-cognitive function (P = .03). Education improved depression (P = .001). No relationship was noted between previous dance experience and improvements. Gains were maintained 3 months after the intervention. Adapted tango may improve mobility, gait and motor-cognitive function more than health education classes in older adults. Further research is necessary to confirm these findings.


[Time, a lever for change].
Race against time, interruptions, operating room tardiness, handover times… Expressions such as these show the significance of time in health professionals' everyday working lives. Health care facilities are no exception. In these structures, time is necessary to accomplish organisational transformation projects for the benefit of patients and users.


The principal projection pathway between the olfactory bulb and the prepyriform cortex in the cat.
The anatomy and neuroelectric properties of the lateral olfactory tract (LOT) were investigated in the cat. Electron micrographs were obtained from sampled areas across the rostro-caudal projection of the pathway. Fiber diameters were estimated and axon spectra were obtained from three regions corresponding to peduncle, mid-LOT, and caudal-LOT. The mean inside diameter for all measured axons was 1.13 +/- 0.53 microns. The greatest number was found in the peduncle (approximately 600,000 axons). Mid-LOT and caudal-LOT each contained approximately 250,000 axons. Unmyelinated processes were estimated to be more numerous than the myelinated axons. Synaptic structures were also observed in the LOT. Cross-sectional area measurements of the LOT were obtained from tissue prepared for light microscopy. The area decreased from about 0.3 to 0.2 mm2 across the projection from olfactory bulb to cortex. The anatomical data were used to predict the conduction properties of transmission over the LOT. The olfactory bulb mitral cells were stimulated electrically and conduction velocity and temporal dispersion were evaluated in the tract. The strength-duration and stimulus-response curves and the potential profile during stimulation were also obtained. The time constant for LOT axons was 0.3 msec. The stimulus-response curve was sigmoidal in shape for both presynaptic and postsynaptic responses. The relationship between input (the action potentials) and output (cortical postsynaptic potentials) was linear up to 90 times threshold. Action potentials were conducted at 20 m/sec across the pathway over the peduncle and decreased to about 10 m/sec in caudal aspects. The potential profile for action potentials decayed exponentially into the depths of the cortex whereas the synaptic potential was a surface negative dipole field. The axon spectra were convolved with the electrophysiological properties of the LOT to mathematically reconstruct action potentials. The empirically derived mono- and biphasic curves fitted reasonably well with experimentally derived data under various stimulus conditions.


Risk factors for Pneumocystis carinii pneumonia in patients with polymyositis/dermatomyositis or systemic lupus erythematosus.
To investigate risk factors for Pneumocystis carinii pneumonia (PCP) in patients with systemic lupus erythematosus (SLE) and polymyositis/dermatomyositis (PM/DM). The subjects were 75 patients hospitalized because of SLE or PM/DM who were administered corticosteroids 40 mg/day or above as prednisolone. The relationship between clinical symptoms of SLE and PM/DM and the occurrence of PCP was evaluated. Seven patients (9.3%) developed PCP and 3 died. Interstitial pulmonary fibrosis was observed in all 7 patients who developed PCP, and its incidence was significantly higher (p < 0.001) than in those who did not develop PCP (6/68). The incidence of PCP in patients with SLE was 1.7%, but that of patients with PM/DM was 37.5%. The peripheral blood lymphocyte count was 1052.7/microliters in patients who developed PCP, which was significantly lower (p < 0.01) than 1841.6/microliters in patients who did not develop PCP. A low peripheral lymphocyte count and interstitial pulmonary fibrosis were considered risk factors for PCP in patients administered corticosteroids for SLE or PM/DM.


Generalizability of Footwear Traction Performance across Flooring and Contaminant Conditions.
To prevent slip and fall events at the workplace, mechanical slip testing is conducted on shoes. Such experiments may involve redundant testing across floorings and contaminant conditions, causing wasted time and effort. Quantify the correlations between shoe traction across different contaminant-flooring conditions to reduce redundant slip testing efforts. The available coefficient-of-friction (ACOF) was quantified for 17 shoes across five floorings and three contaminant conditions. Redundant testing conditions were identified when the shoe ACOF values for one floor-contaminant condition were highly correlated with a second floor-contaminant condition. High correlations were observed among quarry floorings across different contaminants and among vinyl (composite tile) floorings with the same contaminant. However, vinyl floorings exhibited low correlations with quarry floorings. Low correlations were also observed across contaminants within vinyl tiles. This study was able to determine the generalizability of traction performance of shoes across vinyl and quarry floorings. This information is anticipated to reduce redundant traction testing of shoes across vinyl and quarry floorings.


Occurrence of organochlorine pesticides (OCPs) and their enantiomeric signatures, and concentrations of polybrominated diphenyl ethers (PBDEs) in the Adélie penguin food web, Antarctica.
Concentrations and enantiomeric signatures of organochlorine pesticides were determined in Antarctic krill, emerald rockcod and Adélie penguin from the Ross Sea, Antarctica. HCB and DDTs were prevalent contaminants in penguin eggs. The highest concentrations of SigmaHCHs (1.35 +/- 0.72 ng/g) were found in the rockcod muscle, where gamma-HCH (1.23 +/- 0.67 ng/g) was the principal isomer. The ratio gamma-HCH/alpha-HCH was evaluated. Enantioselective gas chromatography was used for the evaluation of enantiomeric fractions (EFs) for alpha-HCH and oxychlordane. An increase of 14% in the (+)alpha-HCH enantiomer was found from krill through penguin, suggesting the enantioselective biotransformation increased proportionately with trophic level. Polybrominated diphenyl ethers (PBDEs) were measured and their concentrations were 5.6 +/- 1.12, 5.81 +/- 2.32, 4.57 +/- 0.17 and 3.06 +/- 3.27 ng/g lipids in krill, rockcod muscle, rockcod homogenate and penguin eggs, respectively. The detection of BDE28, BDE47, BDE99 and BDE100 in Antarctic organisms confirmed their global transport and distribution; the detection of lower brominated congeners suggested a potential long-range transport.


The legacy of trace metal deposition from historical anthropogenic river management: A regional driver of offshore sedimentary microbial diversity.
River management, both modern and historical, have dramatically modified offshore environments. While numerous studies have described the modern impacts, very few have evaluated the legacies remaining from hundreds of years ago. Herein, we show trace metal enrichment in the surface sediment of the abandoned Yellow River Delta, hypothesized to be associated with ancient river management. Essentially, anthropogenic modification caused the river to shift, creating a 12.4×103 km2 area with elevated trace metals; characterized by clear metal deposition gradients. Geographical factors related to the ancient river mouth had the most significant influences on Zn (explained by distance to the river mouth, DTM) and Cd (DTM and sediment salinity), while the sediment absorptive capacity was associated with the reallocation of Cu (clay, silt, and iron), Ni (clay and iron), and Pb (silt and iron). Trace metal legacies showed stronger influences on prokaryotic diversity than on micro-eukaryotic diversity, with the former best described by changes in rare, rather than dominant families and classes, and explainable by an "overlapping micro-niche" model. The ancient river's legacies provide evidence of longer-term human disturbance over hundreds of years; as its impacts on associated benthic microbiomes have led to lessons for modern-day waterway management of benthic ecosystems.


COVID-19 case-fatality variations with application to the Middle East countries.
During a pandemic outbreak, it is important for health officials to know the proportions of deaths among infected individuals and to understand how these proportions change overtime, to accurately predict the impact of the pandemic and to implement effectively new intervention policies and health protocols and to adjust them accordingly. However, most studies where efforts have been made to estimate accurately the case fatality rates did not address the issue of measuring the dynamics of the pandemic deadliness during its course. Daily data on COVID-19 cases and deaths were collected from selected MENA countries. In this paper, two new measures of the pandemic fatality are developed based on the estimated time it takes hospitalized infected patients to eventually die from the disease. The first measure assigns COVID-19 deaths to its most significant lagged number of cases based on a fixed-effects panel data model. The second fatality measure relates pandemic deaths and cases based on their respective change points. The results find notable variations of the pandemic lethality between the Middle East countries, likely due to the difference in the quality of health care. Although crude case-fatality rate does not identify the pandemic lethality variations during the ongoing of the disease, this paper develops two novel measures for COVID-19 case fatality which can identify the dynamics and the variations of the pandemic deadliness.


Brain tumours result in sleep disorders in children and adolescents.
Sleep disturbances are frequently reported in children with brain tumours. The objective of our cross-sectional study was to systematically examine sleep in these children. We hypothesised that children with tumours involving the sleep-wake-regulatory areas have an altered sleep-wake-regulation. Sixty-one patients aged 0-18 years and with a diagnosis of a primary brain or cervical medullary tumour were included. They were categorised based upon tumour location into two groups - those affecting the sleep-wake regulatory regions, i.e. brain stem, basal forebrain, hypothalamus, thalamus, and posterior fossa compressing the brain stem and those that did not. Sleep history, questionnaire surveys, polysomnography, and multiple sleep latency test were used, as indicated clinically. Surveys included Pediatric Daytime Sleepiness Scale, Children's Sleep Habits Questionnaire, Strengths and Difficulties Questionnaire, and Pediatric Quality of Life Inventory, Multidimensional Fatigue Scale and Generic Core Scale. Patients with tumours involving the sleep-wake regulatory areas were sleepier/more fatigued (p = 0.03). Sleep apnoea was observed in 86% of all the patients and comorbid narcolepsy in 8%, without group differences (p ≥ 0.12). Patients with tumours involving the sleep-wake-regulatory areas had more emotional problems (p = 0.04), were more affected by mental health problems (p < 0.001), and had poorer quality of life (p ≤ 0.03). Many children with brain tumours suffer from disturbed sleep, poor mental health, and low quality of life. We recommend that systematic sleep evaluation is included in their routine care along with psychological and social support.


Pathologies at the nexus of blood coagulation and inflammation: thrombin in hemostasis, cancer, and beyond.
Thrombin is the protease involved in blood coagulation. Its deregulation can lead to hemostatic abnormalities, which range from subtle subclinical to serious life-threatening coagulopathies, i.e., during septicemia. Additionally, thrombin plays important roles in many (patho)physiological conditions that reach far beyond its well-established role in stemming blood loss and thrombosis, including embryonic development and angiogenesis but also extending to inflammatory processes, complement activation, and even tumor biology. In this review, we will address thrombin's broad roles in diverse (patho)physiological processes in an integrative way. We will also discuss thrombin as an emerging major target for novel therapies.


Removal of humic acid interference in soil enzymatic analysis using poly-γ-glutamic acid.
Soil enzymes are biological indicators in environmental and agricultural monitoring. However, brownish humic acid (HA) in samples interferes significantly with various analytical methods, especially in optical-based techniques. Here, we implemented a coagulation-flocculation process to carry out continuously an enzymatic reaction without separation and transfer of a sample solution. The elimination of HA in a soil suspension using poly-γ-glutamic acid (PGA) by coagulation to minimize the HA interference in soil enzymatic analysis was investigated. As a result of the optimization of preliminary parameters, the removal efficiency of HA was > 92% in 100 mg L-1 HA in neutral pH, using 100 mg L-1 PGA and aluminum trivalent as a coagulant aid. However, the fluorescent intensity of the enzyme product (i.e., 4-methylumbelliferone) decreases by about 50% as HA was removed under the conditions used. A decrease in the enzymatic detection of 3,3',5,5'-tetramethylbenzidine (TMB) was not observed from treated samples even though the initial level of HA was different. The results suggested that the coagulation-flocculation approach is suitable for the reduction of HA interference, while maintaining target analyte detection. Therefore, the proposed sample treatment can be used to examine enzyme activity based on TMB product detection without regular standard addition calibration.


P2 receptors in cancer progression and metastatic spreading.
Tumor microenvironment is nucleoside and nucleotide rich. Adenosine is a key determinant of the highly immunosuppressive tumor interstitium. Extracellular ATP also affects anti-tumor immunity, albeit its effects on host-tumor interaction are incompletely understood. We give here an overview of recent literature covering the role of nucleotide-selective (P2) plasma membrane receptors in tumor growth and progression. P2 receptors are expressed on both host and cancer cells, where depending on the receptor subtype, the inflammatory infiltrate and the tumor cell type they may drive an anti-tumor response or promote tumor progression. It is anticipated that knowledge of the pharmacology, biochemistry and functional activity of the P2 receptors will allow a better understanding of host-tumor interaction and the development of innovative anti-cancer therapy.


Equality in obstetrical care: racial/ethnic variation in group B streptococcus screening.
The objective of this article is to determine whether racial/ethnic disparities exist in screening for group B streptococcus (GBS) colonization among pregnant women. A retrospective cohort study of deliveries at a single institution was conducted. The primary outcome was the availability of GBS culture data at the time of delivery; the primary predictor was maternal race/ethnicity. Analyses were stratified by the time periods before and after the CDC recommendations for universal screening for GBS. Among 16,333 deliveries, 60.4% of the population was screened for GBS but screening rates varied markedly by year of delivery. Black women had a lower odds of having available GBS data (AOR 0.81 [0.69, 0.95]) but this disparity was limited to the period of time before universal screening was recommended. Prior to the recommendation for universal screening for GBS, racial/ethnic disparities existed in rates of screening among pregnant women delivering at term. These differences were reduced after 2002, suggesting that uniform policies regarding obstetrical care may be effective in eliminating disparities in obstetrical care and outcomes.


Advance care and resuscitation plans in a tertiary hospital: a multimodal approach.
Advance care planning (ACP) is the process of documenting a person's preference for medical treatment in the event of future deterioration. This audit aimed to improve discussion and documentation of ACP in patients who die during a hospital admission. We performed a clinical audit in 2021 of inpatients at a tertiary hospital in Sydney, Australia to evaluate the benefit of multimodal interventions to improve ACP compared with previous audits from 2016 and 2011. In 2021, 97% of audited patients had a documented ACP prior to death compared with 80% in the 2016 audit. The completion of NFR documentation on admission in 2016 was 33%, while in 2021 65% of ACPs were completed within 24 hours of admission.In 2021, 94% of patients had a paper resuscitation form filled; however, identification stickers, which are associated with risk of error, were used in 64%; and 25% of forms were only partially completed. Palliative care was consulted for 44% of patients prior to death; 33% on the day of or prior to death. Improvement in prevalence and timing of ACP prior to death is seen in the postintervention audit. A repeat audit in 5 years will be conducted, with interventions focused on improving documentation of ACP.


Successful laparoscopic distal gastrectomy with D2 lymph node dissection preserving the common hepatic artery branched from the left gastric artery for advanced gastric cancer with an Adachi type VI (group 26) vascular anomaly.
We report a case of successful laparoscopic distal gastrectomy with D2 lymph node dissection preserving the common hepatic artery branched from the left gastric artery for advanced gastric cancer with an Adachi type VI (group 26) vascular anomaly. A 76-year-old female patient was admitted with a diagnosis of advanced gastric cancer at the anterior wall to the lesser curvature of the antrum (cT3N0M0 cStage IIA). Dynamic computed tomography showed the ectopia of the common hepatic artery branched from the left gastric artery. We made a diagnosis of an Adachi type VI (group 26) vascular anomaly and performed the abovementioned operation. In this anomaly pattern, scrupulous attention is required to remove the suprapancreatic lymph nodes because the portal vein is located immediately dorsal to those lymph nodes and is at increased risk for the injury in this situation. The common hepatic artery is branched from the left gastric artery, and the hepatic perfusion from the superior mesenteric artery is not present in group 26. Planning to preserve the artery will improve safety when it is possible oncologically. There were no postoperative complications, and the patient was discharged 9 days after the operation. To our knowledge, the present case is the first reported case of a laparoscopic distal gastrectomy with D2 lymph node dissection with an Adachi type VI (group 26) vascular anomaly. Preoperative diagnostic imaging is very important to prevent surgical complications because the reliable identification of vascular anomaly during an operation is very difficult.


Intravenous anesthesia provides optimal surgical conditions during microscopic and endoscopic sinus surgery.
Controlled hypotension is used to improve surgical conditions during microscopic and endoscopic sinus surgery. New short-acting anesthetics such as propofol and remifentanil allow exact control of intraoperative blood pressure and thus might be valuable tools to improve intraoperative conditions for the otorhinolaryngological surgeon. Intravenous anesthesia was compared with traditional balanced anesthesia by subjective assessment of surgical conditions made by two experienced otorhinolaryngological surgeons. Prospective, randomized, patient- and observer-blinded study. Ninety consecutive patients were randomly assigned to receive intravenous anesthesia with propofol 5 to 8 mg.kg-1.h-1 and remifentanil 10 to 30 microg.kg-1.h-1 or with isoflurane (0.4-1.0 vol%) and repetitive doses of 0.5 to 1 mg alfentanil. An injectable vasodilator was used in both groups to keep mean arterial pressure between 60 and 70 mm Hg (8-9.3 hecto-pascal). The attending otorhinolaryngological surgeon was unaware of the type of anesthesia administered. Immediately after the operation the surgeons rated surgical conditions (bleeding from the surgical field) on a visual analogue scale (0-10 cm) and on a verbal rating scale. Blood pressure was not different between the two groups, but heart rate was lower in the intravenous anesthesia group (mean heart rate in the intravenous anesthesia group, 62 beats per min [95% confidence interval, 52-72]; mean heart rate in the balanced anesthesia group, 75 beats per min [95% confidence interval, 67-83]). Surgical conditions were rated to be significantly better (P <.0001) during anesthesia with propofol-remifentanil (median rating: 2.8; 25th/75th percentile: 2.0/3.4) compared with isoflurane-alfentanil (median rating: 4.9; 25th/75th percentile: 3.6/7.6). Intravenous anesthesia using propofol-remifentanil provides better surgical conditions compared with a traditional balanced anesthesia technique using isoflurane-alfentanil. It is hypothesized that lower cardiac output caused by decreased heart rate during deep general anesthesia is responsible for this result.


The effect of propranolol on hypoglycaemia. Observations in five insulinoma patients.
Five hypoglycaemic hyperinsulinaemic patients (three with proven benign insulinoma, one with proven metastasizing insulinoma, one with probable insulinoma not found at surgery) were treated with propranolol for a variable time ranging from two weeks to one year. Three patients showed favourable clinical results and a significant increase of the mean basal blood glucose level was found while two patients showed no improvement of the frequency of neuroglycopenic episodes and no significant increase of their mean blood glucose level. No patient showed a significant decrease in mean basal IRI concentration. A decrease of insulinaemic responses was observed during oral and intravenous glucose tolerance tests, a prolonged fast, and tolbutamide and glucagon tests performed in some patients. The results suggest that propranolol may induce in certain patients an improvement of basal clinical status through not understood effects (probably hepatic), which leave the peripheral concentrations of insulin unchanged, whereas inhibition of insulin secretion may represent the main way by which the improvement of metabolic situation during physiological or pharmacological stimulation may have been achieved.


First trimester ultrasound: current approaches and practical pitfalls.
Revolutionary technological improvements and high-frequency transvaginal scanning have enabled the resolution of ultrasound imaging in the first trimester to increase such that detailed early fetal development can now be well visualized. This investment in imaging technology has enabled not only normal embryonic development but also chromosomal abnormalities and structural anomalies to be more easily and accurately diagnosed before the second trimester. This article is intended to help radiologists in the interpretation and clinical application of normal and abnormal first trimester ultrasound findings in early pregnancy. We review the current literature and applications and interpretations of first trimester ultrasound.


A systematic review examining caregivers' of color experiences with the diagnostic process of autism spectrum disorder.
Children of color are diagnosed with autism later than White children. Caregivers of color are also more likely than White caregivers to report that their child's healthcare providers do not treat them as a partner, spend enough time with them, or respect their culture and values. We wanted to better understand the experiences of caregivers of color with the diagnostic process of autism spectrum disorder, from the time they discuss developmental concerns with their child's primary care provider to when the diagnosis is shared with them. We systematically reviewed the literature and found 15 articles that explored the experiences of caregivers of color. Caregivers of color described that they faced large-scale barriers, such as the cost of appointments, transportation, and long wait lists. They also reported negative experiences with providers, including providers not taking their concerns seriously, making assumptions about caregivers, and delaying referrals for an evaluation. Caregivers stated that their own lack of knowledge of autism spectrum disorder, stigma, their family's thoughts and opinions, and cultural differences between providers and caregivers served as barriers during the diagnostic process. Communication challenges were discussed and included use of medical and technical jargon, a lack of follow-up, language barriers, and difficulty obtaining high-quality interpreters. Some families described providers, other individuals, community networks, and self-advocacy as helpful during the diagnostic process. Large-scale changes are needed, such as increases in the number of providers who are trained in diagnosing Autism. Provider-level changes (e.g. implicit bias training) are also important for improving caregivers' experiences.


An efficient synthesis of chiral phosphinyl oxide pyrrolidines and their application to asymmetric direct aldol reactions.
Chiral pyrrolidine-based phosphinyl oxides were synthesized and their performance as organocatalysts for asymmetric direct aldol reactions was evaluated. High enantioselectivities and diastereoselectivies were achieved for a range of cyclic ketones and aromatic aldehydes.


Evaluation of Pulse Oximetry Knowledge of Greek Registered Nurses.
Proper use and evaluation of the pulse oximeter readings in everyday clinical practice are related to patient safety and quality of provided patient healthcare. Purpose of this study was the evaluation of Greek registered nurses' knowledge in pulse oximetry before and after an educational intervention implemented in a 2-h educational intervention (workshop). Anonymous self-administered validated questionnaire consisted of two parts was used to collect the data, after the written consent of the author, in a sample consisted of 78 participants (12 men and 66 women) and the output data were analyzed with SPSS v. 19.0 (SPSS Inc., Chicago, IL). The quantitative variables are expressed as mean values (SD) or as median values (interquartile range = IQR) while the qualitative variables are expressed as absolute and relative frequencies. For the comparison of the proportions of the correct answers before and after the intervention, Mc Nemar tests were used. A knowledge score was computed for every participant from all correct answers and converted to a scale from 0 to 100 (where 0 = none correct answer and 100 = all answers were correct). Paired Student's t-tests were used for the comparison of the knowledge score before and after the intervention. All reported p values are two-tailed and the statistical significance was set at p < 0.05. The mean knowledge score increased significantly from 73.4 to 80.5% after the intervention. The study showed that the implementation of educational programs contributes positively to update registered nurses' Knowledge on clinical issues, which cannot be replenished only through undergraduate education and experience.


Defective pantomime of object use in left brain damage: apraxia or asymbolia?
Disturbance of pantomime of object use in patients with left brain damage (LBD) and aphasia has been firmly established but its nature remains controversial. It may be due to an inability to perform movements from memory without external support by objects (apraxia) or to an inability to produce signs referring to absent objects and actions (asymbolia). The need to perform movements without external support is shared with imitation of gestures, and the demand to designate absent objects with drawing from memory. Both of these tasks have been found to be impaired in LBD. We examined pantomime of object use, drawing objects from memory, imitation of meaningless gestures, and aphasia in 40 patients with LBD and aphasia and compared them to healthy controls and to patients with right brain damage (RBD). Whereas drawing showed comparable sensitivity to LBD and RBD, pantomime was distinctly more disturbed in LBD than in RBD patients. Pantomime was worse than drawing in LBD but better than drawing in RBD. In the LBD group scores on pantomime showed significant correlations of very similar strength to drawing, imitation, and all language tests. Multidimensional scaling of the correlational structure placed pantomime in an intermediate position between verbal and non-verbal tests. We conclude that neither apraxia nor asymbolia can satisfactorily explain our results. It seems as if pantomime of object use taps a central aspect of left hemisphere function which is compromised by any LBD. We propose that this may be the ability to select and combine distinctive features of objects and actions.


Primary leiomyosarcoma of the thoracic aorta presenting as a contained rupture.
Primary neoplasms of the aorta are rare and usually present with signs and symptoms due to intraluminal obstruction. A case of a 48-year-old man who presented with a contained rupture of the thoracic aorta secondary to a leiomyosarcoma is reported.


Somatosensory evoked potentials to mechanical disturbances of positioning movements in man: gating of middle-range components.
Somatosensory evoked potentials (SEPs) and EMG responses to mechanical disturbances of positioning movements of the index finger were recorded from normal subjects who performed smooth flexions against the constant load of a torque motor in order to reach a specified target zone. According to a random series 60% of the movements were disturbed by step increases or decreases of the load which subjects had to compensate for (movement condition, MC). As control procedures (a) the same stimuli were applied while the subject had to maintain a constant finger position against the same load (hold condition, HC), and (b) comparable mechanical stimuli were administered to the stationary relaxed finger (resting condition, RC). In MC and HC, the EMG responses consisted of a long-latency (53-61 msec) reflex component, and a 'voluntary' component (98-134 msec). In all 3 conditions, the sequential SEP deflections measured over the sensorimotor cortex included peaks P85 (ipsilateral), N150 (bilateral) and P220 (bilateral). A contralateral N90 component (onset latency 55-60 msec), present in HC and RC, was markedly reduced or absent in MC. Neither in the preceding nor in the consecutive SEP components were there any significant condition-dependent differences, though the N150 showed a trend to diminished amplitude in MC as well. The suppression of SEP components in MC is discussed in terms of efferent and afferent 'gating' actions exerted on the somatosensory input during movement.


How antigen specificity directs regulatory T-cell function: self, foreign and engineered specificity.
Regulatory T cells (Tregs) are a suppressive subset of T cells that have important roles in maintaining self-tolerance and preventing immunopathology. The T-cell receptor (TCR) and its antigen specificity play a dominant role in the differentiation of cells to a Treg fate, either in the thymus or in the periphery. This review focuses on the effects of the TCR and its antigen specificity on Treg biology. The role of Tregs with specificity for self-antigen has primarily been studied in the context of autoimmune disease, although recent studies have focused on their role in steady-state conditions. The role of Tregs that are specific for pathogens, dietary antigens and allergens is much less studied, although recent data suggest a significant and previously underappreciated role for Tregs during memory responses to a wide range of foreign antigens. The development of TCR- or chimeric antigen receptor (CAR)-transduced T cells means we are now able to engineer Tregs with disease-relevant antigen specificities, paving the way for ensuring specificity with Treg-based therapies. Understanding the role that antigens play in driving the generation and function of Tregs is critical for defining the pathophysiology of many immune-mediated diseases, and developing new therapeutic interventions.


Quantitation of glutathione S transferase-pi in the urine of preterm neonates.
Glutathione S transferases (GSTs) are widely distributed enzymes found in highly varying amounts in tissues of the human body. The enzyme GST-pi in urine has been used as a marker of renal distal tubular cell damage. The present study was intended to evaluate urinary excretion of GST-pi and its relationship to other renal markers and to the status of oxidative stress in preterm neonates. Levels of urinary GST-pi, N-acetyl-beta-glucosaminidase (a marker of proximal tubular damage), albumin (a marker of glomerular damage) and 8-hydroxy-2'-deoxyguanosine (a marker of oxidative stress) and serum creatinine were measured in preterm neonates at 1 and 4 weeks of age. The results showed that urinary excretion of GST-pi is increased in preterm neonates compared with reported values for healthy adults. No significant relationship was detected between urinary GST-pi and other markers for renal function. Urinary GST-pi showed significantly positive correlation with urinary 8-hydroxy-2'-deoxyguanosine at 1 and 4 weeks. Sick neonates treated with supplemental oxygen and mechanical ventilation showed significantly higher levels of GST-pi as well as 8-hydroxy-2'-deoxyguanosine than clinically stable neonates did at 4 weeks. These results indicate the potential effect of systemic oxidative stress on urinary excretion of GST-pi. Further studies are necessary to explore the effect of oxidative conditions on expression of GST-pi in distal tubules in the human kidney.


Standardizing microcolposcopy. Assessing the criteria for evaluating the presence and degree of cervical intraepithelial neoplasia.
We established criteria for the detection and grading of cervical intraepithelial neoplasia with microcolposcopy. These criteria were assessed for their accuracy through comparison with the histologic evaluation of cone biopsy or hysterectomy specimens in 26 highly selected cases. There was a positive correlation of 88.5% and no false-negative cases. Microcolposcopy, performed in a standardized manner, may be a valuable adjuvant to colposcopy.


Time dependent impact of perinatal hypoxia on growth hormone, insulin-like growth factor 1 and insulin-like growth factor binding protein-3.
Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we examined acute and subacute correlations between neuronal degeneration and serum growth factor changes, including growth hormone (GH), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after hypoxic-ischemia (HI) in neonatal rats. In the acute phase of hypoxia, brain volume was increased significantly as compared with control animals, which was associated with reduced GH and IGF-1 secretions. Reduced neuronal survival and increased DNA fragmentation were also noticed in these animals. However, in the subacute phase of hypoxia, neuronal survival and brain volume were significantly decreased, accompanied by increased apoptotic cell death in the hippocampus and cortex. Serum GH, IGF-1, and IGFBP-3 levels were significantly reduced in the subacute phase of HI. Significant retardation in the brain and body development were noted in the subacute phase of hypoxia. Here, we provide evidence that serum levels of growth-hormone and factors were decreased in the acute and subacute phase of hypoxia, which was associated with increased DNA fragmentation and decreased neuronal survival.


Sensitive determination of aldehyde metabolites in exhaled breath condensate using capillary electrophoresis with laser-induced fluorescence detection.
A novel capillary electrophoresis with laser-induced fluorescence detection method has been developed for the analysis of aldehyde metabolism biomarkers for oxidative stress in exhaled breath condensate (EBC), and fluorescein 5-thiosemicarbazide was used as a derivatization reagent. In a simple capillary zone electrophoresis mode, ten low molecular weight aldehydes (LMWAs) could be well separated within 30 min. The reaction efficiency was doubled by increasing sample solution pH and magnetic stirring, and the LODs of this method reached 0.16-3.4 nM (S/N = 3). Acceptable recoveries (82.1-115%) were obtained for EBC samples, and the RSD data were within 7.9%. This developed method has been applied for the analyses of EBC samples and evaluation of the correlation between smoking and the contents of aldehyde metabolites in EBC. Due to no need of buffer additives and sample preconcentration, this proposed method may provide an appealing alternative for the trace analyses of LMWAs in noninvasive biofluids. Graphical abstract .


Hypovitaminosis D presenting as diffuse myalgia in a 22-year-old woman: a case report.
Caused predominantly by insufficient conversion of vitamin D precursors by sunlight, hypovitaminosis D is an issue of increasing importance worldwide. Although it has been associated with a range of diseases, musculoskeletal effects dominate the clinical picture and can lead to significant physical debility, whether acute or chronic. Although diagnosis of vitamin D deficiency typically occurs in the outpatient setting, it is an easily treatable condition, and timely intervention can dramatically improve one's quality of life. As highlighted by this case report, hypovitaminosis D may be an important but underappreciated etiology of undifferentiated myalgia that, when present, warrants initiation of vitamin D repletion therapy even from the emergency department (ED). A 22-year-old African-American female presented to our ED with diffuse myalgia for 4 months. She reported significant debility from these symptoms with difficulty ambulating and performing activities of daily living. There had been no upper respiratory infection symptoms. The patient had discussed all of this with her primary care physician who, despite an extensive laboratory work-up, had not identified a definitive etiology. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Chronic pain has stricken the ED patient population across the board. Studies demonstrate that the myalgia caused by hypovitaminosis D can have a profound and negative impact on an individual's lifestyle. Our patient was found to have hypovitaminosis D and had substantial improvement with her myalgia and quality of life after treatment. The purpose of this report is to help the emergency physician appreciate this disease and consider it when clinically appropriate.


Significance of proton relaxation time measurement in brain edema, cerebral infarction and brain tumors.
We examined the proton relaxation times in vitro in various neurological diseases using experimental and clinical materials, and consequently obtained significant results for making a fundamental analysis of magnetic resonance imaging (MRI) as followings. 1) In the brain edema and cerebral infarction, T1 prolonged and T2 separated into two components, one fast and one slow. Prolongation of T1 referred to the volume of increased water in tissue. The slow component of T2 reflects both the volume and the content of increased edema fluid in tissue. 2) In the edematous brain tissue with the damaged Blood-Brain-Barrier (BBB), the slow component of T2 became shorter after the injection of Mn-EDTA. Paramagnetic ion could be used as an indicator to demonstrate the destruction of BBB in the brain. 3) After the i.v. injection of glycerol, the slow component of T2 became shorter in the edematous brain with the concomitant decrease of water content. The effects of therapeutic drug could be evaluated by the measurement of proton relaxation times. 4) Almost all tumor tissue showed a longer T1 and T2 values than the normal rat brain, and many of them showed two components in T2. It was difficult to determine the histology of tumor tissue by the relaxation time alone because of an overlap of T1 and T2 values occurred among various types of brain tumors. 5) In vivo T1 values of various brain tumor were calculated from the data of MRIs by zero-crossing method, and they were compared with the in vitro T1 values which were measured immediately after the surgical operation. Though the absolute value did not coincide with each other due to differences in magnetic field strength, the tendency of the changes was the same among all kinds of tumors. It is concluded that the fundamental analysis of proton relaxation times is essentially important not only for the study of pathophysiology in many diseases but also for the interpretation of clinical MRI.


Ventricular tachycardia following naloxone administration in an illicit drug misuse.
A case of ventricular tachycardia in a 37-year-old man after ingestion of heroin and cocaine, treated with naloxone is described. The arrhythmia is attributed to unopposed sympathomemetic effects of cocaine following administration of naloxone. The pro-rhythmogenic effects of naloxone may have contributed to the arrhythmia. He was initially treated sequentially with intravenous magnesium sulphate, calcium gluconate, sodium bicarbonate and lignocaine infusion, with no resolution of the ventricular tachycardia. He was admitted to the coronary care unit and was given an amiodarone infusion which converted the rhythm to sinus rhythm. Forensic physicians administering naloxone to poly-drug abuser in a custodial setting should be aware of potentially fatal consequences which they will be unable to detect. It is recommended that all such patients should be transferred to hospital for observation and investigation.


Do patients bypass primary care for common health problems under a free-access system? Experience of Taiwan.
A common challenge for free-access systems is that people may bypass primary care and seek secondary care through self-referral. Taiwan's government has undertaken various initiatives to mitigate bypass; however, little is known about whether the bypass trend has decreased over time. This study examined the extent to which patients bypass primary care for treatment of common diseases and factors associated with bypass under Taiwan's free-access system. This repeated cross-sectional study analyzed data from Taiwan's National Health Insurance Research Database. A random sample of 1 million enrollees was drawn repeatedly from the insured population during 2000-2017. To capture visits beyond the community level, the bypass rate was defined as the proportion of self-referred visits to the top two levels of providers, namely academic medical centers and regional hospitals, among all visits to all providers. Subgroup analyses were conducted for visits with a single diagnosis. Logistic regressions were used to investigate factors associated with bypass. The standardized bypass rate for all diseases analyzed exhibited a decreasing trend. In 2017, it was low for common cold (0.7-1.3%), moderate for hypertension (14.0-29.5%), but still high for diabetes (32.0-47.0%). Moreover, the likelihood of bypass was higher for male, patients with higher salaries or comorbidities, and in areas with more physicians practicing in large hospitals or less physicians working in primary care facilities. Although the bypass trend has decreased over time, continuing efforts may be required to reduce bypass associated with chronic diseases. Both patient sociodemographic and market characteristics were associated with the likelihood of bypass. These results may help policymakers to develop strategies to mitigate bypass.


Muscle contraction velocity, strength and power output changes following different degrees of hypohydration in competitive olympic combat sports.
It is habitual for combat sports athletes to lose weight rapidly to get into a lower weight class. Fluid restriction, dehydration by sweating (sauna or exercise) and the use of diuretics are among the most recurrent means of weight cutting. Although it is difficult to dissuade athletes from this practice due to the possible negative effect of severe dehydration on their health, athletes may be receptive to avoid weight cutting if there is evidence that it could affect their muscle performance. Therefore, the purpose of the present study was to investigate if hypohydration, to reach a weight category, affects neuromuscular performance and combat sports competition results. We tested 163 (124 men and 39 woman) combat sports athletes during the 2013 senior Spanish National Championships. Body mass and urine osmolality (UOSM) were measured at the official weigh-in (PRE) and 13-18 h later, right before competing (POST). Athletes were divided according to their USOM at PRE in euhydrated (EUH; UOSM 250-700 mOsm · kgH2O(-1)), hypohydrated (HYP; UOSM 701-1080 mOsm · kgH2O(-1)) and severely hypohydrated (S-HYP; UOSM 1081-1500 mOsm · kgH2O(-1)). Athletes' muscle strength, power output and contraction velocity were measured in upper (bench press and grip) and lower body (countermovement jump - CMJ) muscle actions at PRE and POST time-points. At weigh-in 84 % of the participants were hypohydrated. Before competition (POST) UOSM in S-HYP and HYP decreased but did not reach euhydration levels. However, this partial rehydration increased bench press contraction velocity (2.8-7.3 %; p < 0.05) and CMJ power (2.8 %; p < 0.05) in S-HYP. Sixty-three percent of the participants competed with a body mass above their previous day's weight category and 70 of them (69 % of that sample) obtained a medal. Hypohydration is highly prevalent among combat sports athletes at weigh-in and not fully reversed in the 13-18 h from weigh-in to competition. Nonetheless, partial rehydration recovers upper and lower body neuromuscular performance in the severely hypohydrated participants. Our data suggest that the advantage of competing in a lower weight category could compensate the declines in neuromuscular performance at the onset of competition, since 69 % of medal winners underwent marked hypohydration.


Highly efficient fixation of carbon dioxide into 2-oxazolidinones under mild conditions by using a reusable ionic liquid/CuI catalyst system.
A green approach was proposed for fixing CO2 with high efficiency and minimal energy consumption to produce 2-oxazolidinones through a one-pot reaction under mild conditions. A catalytic system composed of CuI and the ionic liquid [BMMIM][PF6] was employed, resulting in excellent yields. The starting materials, amines, aldehydes, and alkynes, with various substituents were investigated. The ionic liquid [BMMIM][PF6] used in this study was easy to prepare and easy to recycle for repeated use.


Transatrial repair of ventricular septal defects with reference to their anatomic classification.
A consecutive series of 50 children undergoing elective operations for ventricular septal defect (VSD) is presented. Atriotomy was performed routinely. Repair of the defect through the tricuspid valve was attempted in all cases and achieved in 72 percent. There was a 24 percent incidence of right bundle branch block. All patients improved symptomatically after the operation. The mortality rate was 4 percent. The right atrial route is considered to be preferable as a primary approach and has no disadvantages.


[Heart disease and psychogeriatric issues: a complexity model].
In this paper, the most common clinical conditions characterized by cardiac problems and psychogeriatric diseases are discussed. In particular, the impact of depressive disorders and dementia on treatment strategies and on patient's short- and long-term outcome is analyzed.


How far does it get?--The effect of shooting distance and type of firearm on the simultaneous analysis of DNA and RNA from backspatter recovered from inside and outside surfaces of firearms.
When a firearm projectile hits a biological target a spray of biological material (e.g. blood and tissue) is ejected from the entrance wound and propelled back into the direction of the firearm. This phenomenon has been termed 'backspatter' and if backspattered biological material reaches the firearm on its backward trajectory it may persist on and be recovered from the firearm's inside surfaces. Molecular genetic analysis of backspatter generated by contact shots and shots from very short distances has already been demonstrated to critically contribute to victim identification and the reconstruction of firearm-related crimes. It is not known, however, up to what shooting distance can backspatter be found on firearms' inside surfaces and what influence the weapon's type and caliber has on backspatter attributes (e.g. reach, amount and distribution). Therefore, the present pilot study investigated the effect of serval combinations of shooting distances and types of firearms and ammunitions on the analyzability of co-extracted DNA and micro-RNA in samples of backspatter collected from interior and exterior surfaces of the firearms after experimental shootings employing standardized ballistic models. We demonstrate the limiting effect of shooting distance and the type of firearm on the yield of nucleic acids recovered from backspatter and the success rates of forensic DNA profiling and RNA based body-fluid and organ tissue identification in experimental shootings.