Intracranial alveolar echinococcosis in China: discussion of surgical treatment.
Intracranial alveolar echinococcosis is an uncommon disease and difficult to treat. Three patients with central nervous system (CNS) involvement are reported, and the surgical treatment of the monomassive type is emphasized. The largest mass lesion reported, so far, in the literature (9.0 X 6.5 X 4.5 cm) was extirpated in one of our cases. Related problems are discussed in combination with the literature.


Ramelteon Ameliorates LPS-Induced Hyperpermeability of the Blood-Brain Barrier (BBB) by Activating Nrf2.
The blood-brain barrier (BBB) is important for protecting the brain tissue by selectively exchanging substances between the blood and brain. The integrity of the BBB can be damaged by multiple factors, including oxidative stress and inflammation. Ramelteon is an oral hypnotic drug, and in the present study, we investigated its protective effect on BBB damage, as well as the underlying mechanism. LPS was used to induce BBB damage on mice and stimulate injury on endothelial cells. Evans blue staining assay was used to measure the brain permeability. The expressions of ZO-1 and Occludin were evaluated using immunostaining and Western blot in the brain tissue and endothelial cells, respectively. qRT-PCR and ELISA were used to detect the production of IL-1β and MCP-1 in the brain vessels. TBA assay was utilized to examine the concentration of MDA in the brain tissue and endothelial cells. The expression of Nrf2 in the nucleus and NQO1 were determined using Western blot assay. The endothelial permeability of the monolayer was examined using the FITC-dextran permeation assay. Firstly, the increased brain permeability and downregulated expression of tight junction proteins in the brain tissue induced by LPS were significantly reversed by treatment with Ramelteon, accompanied by the decrease in the production of IL-1β and MCP-1 in the vessels in mice. Also, the Nrf2 signaling was activated and oxidative stress in the brain vessels was alleviated by treatment with Ramelteon. Secondly, LPS-induced increase in endothelial monolayer permeability and decrease in tight junction protein expression in bEnd.3 brain endothelial cells were significantly reversed by Ramelteon, accompanied by activated Nrf2 signaling and alleviated oxidative stress. Lastly, the protective effects of Ramelteon against LPS-induced reduction of ZO-1 and Occludin, and the increase in endothelial monolayer permeability were dramatically abolished by silencing Nrf2. Ramelteon might ameliorate LPS-induced hyperpermeability of the BBB by activating the Nrf2 signaling pathway.


Strategies for Recruiting Young African American Men for Primary Stroke Prevention Research.
African American (AA) men bear a disproportionate burden of cardiovascular disease and stroke but are often underrepresented in research. This article describes the development and evaluation of a recruitment plan to reach young AA men for the Stroke Counseling for Risk Reduction in Men project. The plan was developed from researchers' previous experiences and a literature review, and used to recruit AA men, ages 20 to 35 years, for focus groups about stroke and Stroke Counseling for Risk Reduction. Screening survey respondents (N = 81) were reached mostly by word of mouth (42%) and social media (28%). Focus group participants (N = 32) recommended appropriate incentives and social media to recruit young AA men for research. They also suggested learning about the study from a friend, colleague, or study participant could motivate participation. The plan was successful in reaching and enrolling an adequate sample. Findings and recommendations highlight the importance of social networks and trusted sources.


The low synaptic release probability in vivo.
The release probability, the average probability that an active zone of a presynaptic terminal releases one or more vesicles following an action potential, is tightly regulated. Measurements in cultured neurons or in slices indicate that this probability can vary greatly between synapses, but on average it is estimated to be as high as 0.5. In vivo, however, the size of synaptic potentials is relatively independent of recent history, suggesting that release probability is much lower. Possible causes for this discrepancy include maturational differences, a higher spontaneous activity, a lower extracellular calcium concentration and more prominent tonic inhibition by ambient neurotransmitters during in vivo recordings. Existing evidence thus suggests that under physiological conditions in vivo, presynaptic action potentials trigger the release of neurotransmitter much less frequently than what is observed in in vitro preparations.


2,2-Dimethyl-5-[(5-methyl-furan-2-yl)methyl-idene]-1,3-dioxane-4,6-dione.
The asymmetric unit of the title compound, C(12)H(12)O(5), contains two independent mol-ecules. In each, the 1,3-dioxane ring adopts an envelope conformation with the dimethyl-substituted C atom forming the flap. The crystal structure is stabilized by weak inter-molecular C-H⋯O hydrogen bonds.


Hemoproteins in the cold.
This review highlights some aspects of the biochemistry of cold-adapted hemoproteins in fish and bacteria, without claiming to be exhaustive. Heme hexacoordination where the sixth ligand is provided by an internal amino-acid residue, in cold-adapted hemoproteins will be discussed.


Improved use of allied health professionals in the health care system: the case of the advanced practice physiotherapist in orthopedic care.
This article provides an overview of work done in Canada involving the use of physiotherapists in models of collaborative care to enhance orthopedic care and practice. Valuable lessons learned and an important model of collaborative care are summarized. The research around these models of care has also contributed to important scope of practice changes for the profession of physiotherapy.


Localization of liver-type lipase in rat ovaries and its activity during the estrous cycle and lactation.
The conditions for an in vitro assay of liver-type lipase, i.e. an enzyme resembling the lipase releasable from the liver by heparin (liver lipase), in rat ovaries were established. The liver-type lipase activity in the ovaries was almost completely (greater than 95%) located in the corpora lutea and its activity ranged from 0.44 to 0.77 mU per corpus luteum of (pseudo)pregnant rats. Preovulatory ovarian follicles contained very low lipase activity. During the estrous cycle the pattern of lipase activity was similar to that of serum progesterone levels (maximal at diestrus 1 and minimal at diestrus 2). In the individual rats liver-type lipase activity in the ovaries was strongly correlated with serum progesterone and 20 alpha-hydroxyprogesterone. The activity of liver-type lipase also varied during lactation. It was relatively low at an early stage (2-3 days) but increased during later stages of lactation. The serum progesterone level was relatively low in rats lactating for 2-3 or 22-24 days. During the intervening time, its concentrations was elevated. Since serum 20 alpha-hydroxyprogesterone levels varied inversely to progesterone, the total amount of progestagens in blood during lactation remained constant. The cholesterol content of the corpora lutea of the lactating rats was initially high and decreased during the lactation.


Quantitation of blood plasma DNA as an index of in vivo cytotoxicity.
Cell death triggers the release into extracellular spaces of products of chromatin catabolism, particularly of DNA. A sensitive DNA assay has been used to investigate in the mouse whether the quantitation of plasma DNA may be used as an index of in vivo cytotoxicity. It has been found that toxic doses of bacterial lipopolysaccharide, HgCl2, CCl4, cyclophosphamide and hydroxyurea, are responsible for the release of extracellular DNA in plasma, in a dose dependent relationship. In conclusion, quantitation of extracellular DNA may be used for investigating in vivo cell death phenomena induced by toxic agents and drugs. Such a method could be applied to toxicological studies in animals and man.


Combinational system for biodegradation of olive oil mill wastewater phenolics and high yield of bio-hydrogen production.
Olive oil mill wastewater (OMW) is a significant pollutant in the Mediterranean region. In the present contribution, we showed clearly that microorganisms (microalgae and OMW-microflora) activated the biodegradation of OMW-phenolics and produced a high yield of hydrogen (H2). In a closed incubation system, the appropriate adjustment of OMW-pH leads to the establishment of anoxic conditions through the oxygen consumption of microorganisms during the first incubation day. The biodegradation procedure of OMW-phenolics needs oxygen. Therefore, after the establishment of anoxic conditions, the biodegradation stopped and the activation of hydrogenases started, leading to a continuous high yield of bio-hydrogen production. If the cultivation system re-opened (oxygen enrichment), the OMW-phenolic biodegradation (oxygen dependent process) started again and therefore the detoxified OMW could be used for further biotechnological applications (production of biodiesel, bioalcohols, organic fertilizers, etc.). Apart from the environmental compatibility of the method and the sustainability of such a combinational application (OMW detoxification and high yield of hydrogen production) in the context of a green biotechnology approach, the cost/profit ratio appears to be particularly tempting and guarantees its widespread use in the near future. The present contribution proposes a solution to a major environmental problem by upgrading its solution to a high-value product.


Characterization of cholylglycine hydrolase from a bile-adapted strain of Xanthomonas maltophilia and its application for quantitative hydrolysis of conjugated bile salts.
Purified bile salt hydrolase from bile-adapted Xanthomonas maltophilia displays Michaelis-Menten kinetics on cholylglycine and cholyltaurine and hydrolyzes bile salts also in crude bovine bile. The protein is a dimer and is resistant to proteinases and to heating at 55 to 60 degrees C for up to 60 min, in agreement with calorimetric data.


Asymmetry within and around the human planum temporale is sexually dimorphic and influenced by genes involved in steroid hormone receptor activity.
The genetic determinants of cerebral asymmetries are unknown. Sex differences in asymmetry of the planum temporale (PT), that overlaps Wernicke's classical language area, have been inconsistently reported. Meta-analysis of previous studies has suggested that publication bias established this sex difference in the literature. Using probabilistic definitions of cortical regions we screened over the cerebral cortex for sexual dimorphisms of asymmetry in 2337 healthy subjects, and found the PT to show the strongest sex-linked asymmetry of all regions, which was supported by two further datasets, and also by analysis with the FreeSurfer package that performs automated parcellation of cerebral cortical regions. We performed a genome-wide association scan (GWAS) meta-analysis of PT asymmetry in a pooled sample of 3095 subjects, followed by a candidate-driven approach which measured a significant enrichment of association in genes of the 'steroid hormone receptor activity' and 'steroid metabolic process' pathways. Variants in the genes and pathways identified may affect the role of the PT in language cognition.


REM sleep loss increases brain excitability: role of noradrenaline and its mechanism of action.
Ever since the discovery of rapid eye movement sleep (REMS), studies have been undertaken to understand its necessity, function and mechanism of action on normal physiological processes as well as in pathological conditions. In this review, first, we briefly surveyed the literature which led us to hypothesise REMS maintains brain excitability. Thereafter, we present evidence from in vivo and in vitro studies tracing behavioural to cellular to molecular pathways showing REMS deprivation (REMSD) increases noradrenaline level in the brain, which stimulates neuronal Na-K ATPase, the key factor for maintaining neuronal excitability, the fundamental property of a neuron for executing brain functions; we also show for the first time the role of glia in maintaining ionic homeostasis in the brain. As REMSD exerts a global effect on most of the physiological processes regulated by the brain, we propose that REMS possibly serves a housekeeping function in the brain. Finally, subject to confirmation from clinical studies, based on the results reviewed here, it is being proposed that the subjects suffering from REMS loss may be effectively treated by reducing either noradrenaline level or Na-K ATPase activity in the brain.


Prevalence of neurological problems in a community-based sample of paediatric coeliac disease: a cross-sectional study.
The prevalence of and risk factors for neurological problems in childhood coeliac disease (CD) are unclear. We performed a cross-sectional, community-based audit of CD in children diagnosed from January 2010 to December 2016 in Lothian. 79 (28%) of 284 children with CD (201, 70.8% female) (mean age 8.3 years, range of 1-16) had neurological problems. Fifteen (5.3%) had headaches/migraine, 10 (3.5%) anxiety, 8 (2.8%) motor/co-ordination problems / ataxia (there were no patients with ataxia), 7 (2.5%) had behavioural issues, 5 (1.8 %) with ASD, 5 (1.8%) low mood, 4 (1.4%) ADD/ ADHD, 3 (1.1%) seizures and 2 (0.7%) had neuropathy. Neurological problems were more common with later age at CD diagnosis (OR 1.07, 95% CI 1.01 to 1.14) and male gender (OR 1.69, 95% CI 0.96 to 2.95). Prevalence of neurological problems in children with CD in Lothian is lower than published adult CD studies and similar or lower to the reported prevalence in the general childhood population.


Detection of DNA sequences using biotinylated probes.
It was found (1) that biotinylated analogs of dUTP, which contain a biotin molecule covalently bound to the C-5 position of the pyrimidine via an allylamine linker arm, can be used as substrates for DNA polymerase. Figure 1 shows the structure of biotin-11-dUTP, a commonly used substrate for biotinylation by the method of nick translation (2). The substituted DNA molecule will have similar hybridization properties to the un-substituted DNA. After hybridization to the test DNA, the biotin probe can be located by a variety of methods, including incubation with streptavidin-peroxidase conjugate, which will be described here. Fig. 1. Structure of biotin-11-UTP.


Screening for posttraumatic stress disorder in civilian substance use disorder patients: cross-validation of the Jellinek-PTSD screening questionnaire.
This study aimed to cross-validate earlier findings regarding the diagnostic efficiency of a modified version of the Primary Care Posttraumatic Stress Disorder (PC-PTSD) screening questionnaire (A. Prins, P. Ouimette, R. Kimerling, R. P. Cameron, D. S. Hugelshofer, J. Shaw-Hegwer, et al., 2004). The PC-PTSD is a four-item screening questionnaire for Posttraumatic Stress Disorder (PTSD). Based on former research, we adapted the PC-PTSD for use among civilian substance use disorder (SUD) patients (D. Van Dam, T. Ehring, E. Vedel, & P. M. G. Emmelkamp, 2010). This version will be referred to as the Jellinek-PTSD (J-PTSD) screening questionnaire. Results showed a high sensitivity (.87), specificity (.75), and overall efficiency (.77) of the J-PTSD in detecting PTSD when using a cutoff score of 2. This confirms findings in former research, and suggests that the J-PTSD is a useful screening instrument for PTSD within a civilian SUD population. Both PTSD and SUD are severe and disabling disorders causing great psychological distress. An early recognition of PTSD among SUD patients makes it possible to address PTSD symptoms in time, which may ultimately lead to an improvement of symptoms in this complex patient group.


Determinants of medical record access for an epidemiologic study.
Hospital record access is often needed for epidemiologic research. In a recent study, 26 Denver-area hospitals were contacted for permission to review records. The review process, the decision regarding access, and hospital characteristics were analyzed. Hospitals with a review committee, larger hospitals, and those which reached a decision rapidly were most likely to grant access. These results may provide guidance to investigators planning studies requiring review of hospital records.


Cognitive function and associated factors among postmenopausal women with hypertension and natural menopause in Taiwan.
Hypertension is prevalent among postmenopausal women worldwide and is a risk factor for cognitive impairment. This study examined the cognitive differences between Taiwanese postmenopausal women with and without hypertension after natural menopause and identified factors associated with cognitive function in hypertensive postmenopausal women. A two-group comparative design study of 171 Taiwanese postmenopausal participants (mean age = 64.8±6.6) was conducted in southern Taiwan. Cognitive performance on neuropsychological tests was evaluated, and demographic, health, menopausal, and disease related variables were assessed. Compared to the non-hypertensive group, women with hypertension showed significantly worse performance and a higher percentage of impairment in global cognitive functioning and memory. Fewer years of education and longer duration of hypertension were associated with lower global cognitive function, and increased age was associated with lower scores in delayed memory. Cognitive screening as well as training on global cognitive functioning and memory are needed for postmenopausal hypertensive women. (148 words).


Automatically assessed P-wave predicts cardiac events independently of left atrial enlargement in patients with cardiovascular risks: The Japan Morning Surge-Home Blood Pressure Study.
A prolonged P-wave in electrocardiography (ECG) reflects atrial remodeling and predicts the development of atrial fibrillation (AF). The authors enrolled 810 subjects in the Japan Morning Surge Home Blood Pressure (J-HOP) study who had ≥1 cardiovascular (CV) risk factor. The duration of P-wave was automatically analyzed by standard 12-lead electrocardiogram. Left atrial (LA) enlargement and left ventricular hypertrophy (LVH) were measured on echocardiography. The primary end points were fatal/nonfatal cardiac events: myocardial infarction, sudden death, and hospitalization for heart failure. The maximum P-wave duration (Pmax) from the 12 leads was selected for analysis. The authors compared four prolonged P-wave cutoffs (Pmax = 120, 130, 140, 150 ms) and cardiac events. LA diameter and left ventricular mass index (LVMI) were significantly associated with Pmax (r = 0.08, P = .02 and r = 0.17, P < .001, respectively). When the cutoff level was Pmax 120 or 130 ms, prolonged P-wave was not associated with cardiac events (P = .45 and P = .10), but when a prolonged P-wave was defined as Pmax ≥ 140 ms (n = 50) or Pmax ≥ 150 ms (n = 19), the patients in those groups had significantly higher incidence of cardiac events than others (P < .001 and P = .03). A Cox proportional hazards model including age, gender, body mass index, smoking, regular drinker, hypertension, dyslipidemia, diabetes, office systolic blood pressure, heart rate, LA enlargement, and LVH revealed that prolonged P-wave defined as Pmax ≥ 140 ms was independently associated with cardiac events (hazard ratio: 4.23; 95% confidence interval: 1.30-13.77; P = .02). In conclusion, the automatically assessed prolonged P-wave was associated with cardiac events independently of LA enlargement and LVH in Japanese patients with CV risks.


Intragastric safflower yellow and its main component HSYA improve leptin sensitivity before body weight change in diet-induced obese mice.
Our previous studies found that safflower yellow (SY) and its main component hydroxysafflor yellow A (HSYA) could alleviate obesity and improve leptin resistance in high-fat diet (HFD) induced obese mice. Therefore, our present study aimed to investigate whether the above effect of SY/HSYA was a direct effect or follow-up effect of weight loss and whether leptin was essential for the anti-obesity effect of SY/HSYA or not. HFD-induced obese mice were treated with SY or HSYA for 4 weeks, while ob/ob mice were treated with SY for 10 weeks. Body weight, food intake, fat mass, and serum leptin levels were measured. The leptin sensitivity experiment was conducted in HFD-induced obese mice. The expressions of leptin and its signaling-related genes were detected by RT-qPCR and Western blot methods. SY/HSYA treatment had no effect on food intake, energy expenditure, body weight, fat mass, and serum leptin levels in HFD-induced obese mice. However, the leptin sensitivity experiment showed that the food intake decreased by 18.4% in the HFD-SY group and the body weight gain decreased by 104.6% in the HFD-HSYA group, respectively (both P < 0.05). Furthermore, the expressions of leptin and leptin signaling inhibitory regulators were significantly decreased, while the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) were notably increased in WAT of HFD-induced obese mice, fully differentiated 3T3-L1 adipocytes after SY/HSYA intervention (all P < 0.05). Interestingly, SY treatment was ineffective on body weight, fat mass, and glucose metabolism in leptin-deficient ob/ob mice. SY/HSYA administration could firstly improve peripheral leptin resistance in adipose tissue of HFD-induced obese mice before their body weight was significantly changed, and leptin was essential for the anti-obesity effect of SY.


Phospholipase C β3 is Required for Climbing Fiber Synapse Elimination in Aldolase C-positive Compartments of the Developing Mouse Cerebellum.
In the cerebellum of neonatal mice, multiple climbing fibers (CFs) form excitatory synapses on each Purkinje cell (PC). Only one CF is strengthened in each PC from postnatal day 3 (P3) to P7, whereas the other weaker CFs are eliminated progressively from ∼P7 to ∼P11 (early phase of CF elimination) and from ∼P12 to ∼P17 (late phase of CF elimination). Type 1 metabotropic glutamate receptor (mGluR1) triggers a canonical pathway in PCs for the late phase of CF elimination. Among downstream signaling molecules of mGluR1, phospholipase C β3 (PLCβ3) and β4 (PLCβ4) are expressed complementarily in PCs of aldolase C (Aldoc)-positive (+) and Aldoc-negative (-) cerebellar compartments, respectively. PLCβ4 is reported to mediate the late phase of CF elimination in the anterior half of the cerebellar vermis which corresponds to the Aldoc (-) region. However, roles of PLCβ3 and Aldoc in CF synapse elimination are unknown. Here, we investigated CF innervation of PCs in Aldoc-tdTomato knock-in mice that underwent lentivirus-mediated knockdown (KD) of PLCβ3 in PCs during postnatal development. By recording CF-mediated excitatory postsynaptic currents from PCs and immunostaining CF synaptic terminals, we found that significantly higher percentage of PCs with PLCβ3-KD remained multiply innervated by CFs in Aldoc (+) compartments after P12, which was accompanied by impaired elimination of somatic CF synapses and reduced dendritic CF translocation. In contrast, deletion of Aldoc had no effect on CF synapse elimination. These results suggest that PLCβ3 is required for the late phase of CF elimination in Aldoc (+) PCs.


Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study.
Oncogenic alterations in RET represent important therapeutic targets in thyroid cancer. We aimed to assess the safety and antitumour activity of pralsetinib, a highly potent, selective RET inhibitor, in patients with RET-altered thyroid cancers. ARROW, a phase 1/2, open-label study done in 13 countries across 71 sites in community and hospital settings, enrolled patients 18 years or older with RET-altered locally advanced or metastatic solid tumours, including RET-mutant medullary thyroid and RET fusion-positive thyroid cancers, and an Eastern Co-operative Oncology Group performance status of 0-2 (later limited to 0-1 in a protocol amendment). Phase 2 primary endpoints assessed for patients who received 400 mg once-daily oral pralsetinib until disease progression, intolerance, withdrawal of consent, or investigator decision, were overall response rate (Response Evaluation Criteria in Solid Tumours version 1.1; masked independent central review) and safety. Tumour response was assessed for patients with RET-mutant medullary thyroid cancer who had received previous cabozantinib or vandetanib, or both, or were ineligible for standard therapy and patients with previously treated RET fusion-positive thyroid cancer; safety was assessed for all patients with RET-altered thyroid cancer. This ongoing study is registered with clinicaltrials.gov, NCT03037385, and enrolment of patients with RET fusion-positive thyroid cancer was ongoing at the time of this interim analysis. Between Mar 17, 2017, and May 22, 2020, 122 patients with RET-mutant medullary and 20 with RET fusion-positive thyroid cancers were enrolled. Among patients with baseline measurable disease who received pralsetinib by July 11, 2019 (enrolment cutoff for efficacy analysis), overall response rates were 15 (71%) of 21 (95% CI 48-89) in patients with treatment-naive RET-mutant medullary thyroid cancer and 33 (60%) of 55 (95% CI 46-73) in patients who had previously received cabozantinib or vandetanib, or both, and eight (89%) of nine (95% CI 52-100) in patients with RET fusion-positive thyroid cancer (all responses confirmed for each group). Common (≥10%) grade 3 and above treatment-related adverse events among patients with RET-altered thyroid cancer enrolled by May 22, 2020, were hypertension (24 patients [17%] of 142), neutropenia (19 [13%]), lymphopenia (17 [12%]), and anaemia (14 [10%]). Serious treatment-related adverse events were reported in 21 patients (15%), the most frequent (≥2%) of which was pneumonitis (five patients [4%]). Five patients [4%] discontinued owing to treatment-related events. One (1%) patient died owing to a treatment-related adverse event. Pralsetinib is a new, well-tolerated, potent once-daily oral treatment option for patients with RET-altered thyroid cancer. Blueprint Medicines.


Periaortic inflammation after endovascular aneurysm repair.
The periaortitis seen with inflammatory abdominal aortic aneurysms usually resolves after repair by both open and endovascular techniques. Conversely, the de novo development of retroperitoneal fibrosis after endovascular aneurysm repair (EVAR) has also been rarely described, and we present a case and also review the literature. A 63-year-old man underwent EVAR for an asymptomatic, noninflammatory abdominal aortic aneurysm, presenting 9 months subsequently with left loin pain, raised inflammatory markers, and radiological evidence of periaortic inflammation causing significant left ureteric obstruction. Ureteric stenting resolved the hydronephrosis, and the periaortitis improved with combination of steroid and tamoxifen therapy. Periaortitis causing renal impairment after EVAR is a rare complication. Prompt recognition and ureteric stenting helps to prevent long-term renal damage. Steroid and tamoxifen therapy is recommended to treat and avoid recurrence of periaortitis.


The timed up & go test: its reliability and association with lower-limb impairments and locomotor capacities in people with chronic stroke.
To examine test-retest reliability of the Timed Up & Go (TUG) test, its ability to differentiate subjects with chronic stroke from healthy elderly subjects, and its associations with ankle plantarflexor spasticity, ankle muscle strength, gait performance, and distance walked in 6 minutes in subjects with chronic stroke. Cross-sectional study. University-based rehabilitation center in Hong Kong, China. Ten healthy elderly subjects and 11 subjects with chronic stroke. Not applicable. Time taken to complete the TUG test was recorded. Plantarflexor spasticity and ankle muscle strength were assessed, respectively, by the Composite Spasticity Scale and a load-cell together with electromyography. Gait parameters and walking endurance were measured respectively by walkway system (GAITRite II) and 6-minute walk test. Intraclass correlation coefficients (ICCs) were calculated as measures of reliability, and all correlation analyses were conducted using Spearman correlation coefficients. The TUG test showed excellent reliability (ICC>.95). Subjects with chronic stroke had significantly more spastic and weaker plantarflexors, slower walking speeds, and poorer walking endurance when compared with healthy elderly subjects (all P<.003). The strength of the affected ankle plantarflexors (rho=-.860, P<.01), gait parameters (rho range, .620-.900; P<.05), and walking endurance (rho=-.960, P<.01) correlated with TUG scores. The TUG scores were reliable, were able to differentiate the patients from the healthy elderly subjects, and correlated well with plantarflexor strength, gait performance, and walking endurance in subjects with chronic stroke.


Differentiation of peptide isomers and epimers by radical-directed dissociation.
Isomerization and epimerization are spontaneously occurring modifications that represent common pathways for age-related damage in proteins. These modifications accumulate over time and are known to disrupt both structure and function, making their detection and identification an important goal in proteomic characterization. Unfortunately, because these modifications lead to no change in mass, they are typically overlooked in traditional proteomics. Herein we present protocols for mass-spectrometric identification and quantification of protein isomerization and epimerization. Illustrative examples are provided for analysis of crystallin proteins extracted from the eye lens. Crystallins provide an attractive model system for studying the age-related modifications of long-lived proteins due to the lack of protein turnover in the eye lens. We first outline procedures for tissue processing and protein extraction. We then describe methods for data acquisition and analysis for differentiation and identification of isomerized residues, including methods for quantifying isomers which cannot be chromatographically resolved.


Magnetic nanoparticle assemblies on denatured DNA show unusual magnetic relaxivity and potential applications for MRI.
Denatured (substantially single-stranded) herring sperm DNA acts as a template for the preparation of magnetic nanowires, forming stable aqueous suspensions, which exhibit unprecedentedly high relaxivity at low field, suggesting that the material may be a potentially useful reagent for MRI.


Carbonic anhydrase II is induced in HL-60 cells by 1,25-dihydroxyvitamin D3: a model for osteoclast gene regulation.
Carbonic anhydrase II (CA II) generates the H+ required for osteoclast-mediated bone resorption in humans. We have developed the human promyelocytic cell line HL-60 as a model system with which to study the osteoclast-specific expression of the CA II gene. Treatment of the cell line with 1,25-dihydroxyvitamin D3 resulted in a dramatic de novo induction of CA II at both the protein and mRNA levels. CA II mRNA was also induced to a lesser extent by 12-O-tetradecanoyl phorbol 13-acetate. Treatment with dimethyl sulfoxide did not increase CA II mRNA. These findings indicate that the HL-60 cell line will be a useful model system to study the osteoclast-specific expression of the CA II gene.


Palladium-catalyzed asymmetric addition of diarylphosphines to enones toward the synthesis of chiral phosphines.
An asymmetric addition of diarylphosphines to beta-substituted enones under mild conditions using a chiral pincer-palladium catalyst has been developed for the synthesis of chiral phosphines with excellent stereoselectivity (up to 99% ee).


Testing the status-dependent ESS model: population variation in fighter expression in the mite Sancassania berlesei.
The conditional evolutionarily stable strategy (ESS) with status-dependent tactics is the most commonly invoked ESS for alternative reproductive tactics within the sexes. Support for this model has recently been criticized as apparent rather than real. We address key predictions of the status-dependent ESS in three populations of the male dimorphic mite Sancassania berlesei. In S. berlesei'fighter' males are characterized by a thickened pair of legs used for killing rivals; 'scramblers' are benign. Most males in each population could be manipulated to become fighters by decreasing density, fulfilling the prediction that males make a 'decision'. There was evidence of genetic covariance between sire status and offspring morph, but also a strong effect of sire morph on offspring morph ratio. This was consistent with considerable genetic variation for the status-dependent switch point as a breeding experiment found no support for single-locus inheritance. We also found evidence that switch points evolve independently of distributions of status. This study supports the current status-dependent ESS model.


A guide for membrane potential measurements in Gram-negative bacteria using voltage-sensitive dyes.
Transmembrane potential is one of the main bioenergetic parameters of bacterial cells, and is directly involved in energizing key cellular processes such as transport, ATP synthesis and motility. The most common approach to measure membrane potential levels is through use of voltage-sensitive fluorescent dyes. Such dyes either accumulate or are excluded from the cell in a voltage-dependent manner, which can be followed by means of fluorescence microscopy, flow cytometry, or fluorometry. Since the cell's ability to maintain transmembrane potential relies upon low and selective membrane ion conductivity, voltage-sensitive dyes are also highly sensitive reporters for the activity of membrane-targeting antibacterials. However, the presence of an additional membrane layer in Gram-negative (diderm) bacteria complicates their use significantly. In this paper, we provide guidance on how membrane potential and its changes can be monitored reliably in Gram-negatives using the voltage-sensitive dye 3,3'-dipropylthiadicarbocyanine iodide [DiSC3(5)]. We also discuss the confounding effects caused by the presence of the outer membrane, or by measurements performed in buffers rather than growth medium. We hope that the discussed methods and protocols provide an easily accessible basis for the use of voltage-sensitive dyes in Gram-negative organisms, and raise awareness of potential experimental pitfalls associated with their use.


The association of hyperglycemia with the development of infectious complications in adult Filipino patients with acute lymphoblastic leukemia.
Hyperglycemia occurs in Acute Lymphoblastic Leukemia (ALL) due to chemotherapeutic agents and may be stress-induced. Given the potential impact of hyperglycemia on the clinical outcomes of ALL patients, we sought to determine the association of hyperglycemia with the development of infectious complications. This is a retrospective cohort involving adult Filipino ALL patients admitted at a tertiary referral center. Patients were stratified according to blood glucose levels and infections were classified into microbiologically and clinically defined infections. Logistic regression was performed to determine whether hyperglycemia was associated with the development of infectious complications. Of the 174 patients admitted for ALL, only 76 patients (44%) underwent blood glucose monitoring and were thus included in this study. Hyperglycemia was observed in 64 patients (84.21%). Infectious complications were seen in 56 patients (73.68%), of whom 37 patients (48.68%) had microbiologically defined infections and 19 (25%) had clinically defined infections. The respiratory tract was the most common site of infection and gram-negative bacteria were the predominant isolates. Hyperglycemia significantly increased the likelihood of infectious complications, particularly at blood glucose levels ≥ 200 mg/dL. Hyperglycemia is associated with an increased likelihood of infectious complications in Filipino ALL patients. With sepsis being one of the main causes of mortality in this population, our study provides compelling evidence for us to consider routine blood glucose monitoring in order to manage and potentially decrease the occurrence of infections in these patients.


Generation of PARP1 gene knockout human embryonic stem cell line using CRISPR/Cas9.
PARP1 encodes a chromatin-associated enzyme which responsible for post-translational poly(ADP-ribosyl)ation modification (Hsieh et al., 2017). It plays an important role in nucleotide excision repair, non-homologous end joining, DNA mismatch repair and many other DNA repair process. Also, PARP1 participates in inflammation and aging. However, its role in human embryonic stem cell biology has not been fully resolved. To clarify the function of PARP1 in human embryonic stem cells, we reported a PARP1 knockout human embryonic stem cell line, generated by CRISPR/Cas9 mediated gene targeting. This cell line shows normal karyotype, pluripotent stem cell marker expression and differentiation potential in vitro.


Soil fungal and bacterial communities in southern boreal forests of the Greater Khingan Mountains and their relationship with soil properties.
Little is known about the relationship between soil microbial communities and soil properties in southern boreal forests. To further our knowledge about that relationship, we compared the soil samples in southern boreal forests of the Greater Khingan Mountains-the southernmost boreal forest biome in the world. The forests can be divided into boardleaf forests dominated by birch (Betula platyphylla) or aspen (Populus davidiana) and coniferous forests dominated by larch (Larix gmelinii) or pine (Pinus sylvestris var. mongolica). Results suggested different soil microbial communities and soil properties between these southern boreal forests. Soil protease activity strongly associated with soil fungal communities in broadleaf and coniferous forests (p < 0.05), but not with soil bacterial communities (p > 0.05). Soil ammonium nitrogen and total phosphorus contents strongly associated with soil fungal and bacterial communities in broadleaf forests (p < 0.05), but not in coniferous forests (p > 0.05). Soil potassium content demonstrated strong correlations with both soil fungal and bacterial communities in broadleaf and coniferous forests (p < 0.05). These results provide evidence for different soil communities and soil properties in southern boreal forest, and further elucidate the explicit correlation between soil microbial communities and soil properties in southern boreal forests.


Pareto law-based regional inequality analysis of PM2.5 air pollution and economic development in China.
Regional inequality has caused large social and economic problems in China. Numerous researchers have sought to understand the status of economic inequality in the past decades. However, studies are lacking on other aspects of regional inequality, particularly when multiple facets must be considered. In this study, we have innovatively proposed a Pareto law-based method that can help assess multiple dimensions of regional inequality simultaneously. With this approach, we can rank multiple aspects of inequality and provide robust, reasonable goals for different groups of administrative districts. The proposed approach was successfully implemented by using Chinese data for 2015 and 2016, a period during which China was experiencing both severe PM2.5 pollution and economic regional inequality. The results indicate that (1) Shanghai and Shenzhen represent the optimal condition of economic development; (2) different from the spatial distribution of economic inequality alone, inequality was higher in central China for both economic development and PM2.5 air quality; (3) in the context of severe economic inequality in China, the tradeoff between economic development and air quality will result in a relatively equitable condition. In addition, the proposed method is open-ended and can be extended to incorporate more aspects of regional inequality. This approach appears to possess substantial potential for integration into decision-making regarding regional inequality.


Estimation of anatomical structures underneath the chest compression landmarks in children by using computed tomography.
There has been little investigation on the appropriateness of the hand position suggested by various guidelines in paediatric cardiopulmonary resuscitation (CPR). We aimed to identify anatomical structures underneath the chest compression landmarks and tried to find the proper hand position using computed tomography (CT) images for more effective paediatric CPR. This study included a total of 181 paediatric patients who were admitted to Severance Hospital and underwent CTs of chest. We studied structures located under the inter-nipple line and under the lower third of the sternum. The distances from the xiphoid process to the level of the left ventricular outflow tract (LVOT) were measured to find the ceiling on the proper hand position. The LVOT (42.0%) and the root of the aorta (21.5%) were more frequently located than the left ventricle under the inter-nipple line, and the liver was located under the lower third of the sternum in a significant number of patients (28.7%). The LVOT was placed 6.8±13.9 mm below the nipple level, but there was no significant difference in the distance from the nipple level to the LVOT among the age groups (p=0.517). The hand position at the inter-nipple line might be too high and that at the lower third of the sternum might be too low as it can compress the liver. Further studies are needed to find the proper hand position for more effective chest compression during paediatric CPR.


Bombyx mori orphan receptor, BmHR78: cDNA cloning, testis abundant expression and putative dimerization partner for Bombyx ultraspiracle.
We have identified a novel member of the nuclear receptor superfamily from the silkworm Bombyx mori, and named it as BmHR78, the B. mori hormone receptor. The DNA binding domain of BmHR78 shows high similarities to those of Tenebrio molitor hormone receptor 78, Drosophila hormone receptor 78, and mammalian testicular receptor 2, whereas the ligand binding domain is not well conserved. Northern blot analysis showed that BmHR78 gene was most abundantly expressed in the testis. From the fourth to fifth instar, BmHR78 gene was constantly expressed in the testis. In the anterior silk gland, the level of BmHR78 gene expression was developmentally changed. From day 10.0 to 11.0 in the fifth instar, another BmHR78 transcript with the smaller size appeared. Ultraspiracle (USP) isoform also appeared at the same stages in this tissue. BmHR78 forms not only a homodimer, but also a heterodimer with USP in a yeast two hybrid assay. The direct interaction between BmHR78 and USP was confirmed by pull down assay. Deletion mutant analysis showed that BmHR78 interacts with USP via the ninth heptad repeat in helix ten of the E region. This repeat is well conserved in RXR and its heterodimer partners, and shown to be an interface for their dimerization. In insect, only the ecdysone receptor and hormone receptor 38 are known thus far to dimerize with USP. Thus, BmHR78 is a third dimerization partner for USP and may modulate the molecular action of USP, including the ecdysone signal cascades.


Diversification of CDK11 transcripts during chicken testis development and regression.
CDK11 (cyclin-dependent kinase 11, formerly known as PITSLRE) is a serine/threonine kinase that associates with the cyclin L2 regulatory partner. CDK11 catalytic activity has been associated with apoptosis, transcription, and RNA processing. Here, we identify novel chicken testis CDK11 transcripts that differ in their 5'UTR, 3'UTR, splicing of the exon 6, and polyadenylation. We have also characterized the differential expression of CDK11 in somatic tissues, during testis development and upon testicular regression by diethylstilbestrol (DES) treatment. The heterogeneity of CDK11 transcripts presented in this study suggests new possibilities for post-transcriptional regulation.


Pin1 and Alzheimer's disease.
Alzheimer's disease (AD) is an immense and growing public health crisis. Despite over 100 years of investigation, the etiology remains elusive and therapy ineffective. Despite current gaps in knowledge, recent studies have identified dysfunction or loss-of-function of Pin1, a unique cis-trans peptidyl prolyl isomerase, as an important step in AD pathogenesis. Here I review the functionality of Pin1 and its role in neurodegeneration.


The neurobiology of mouse models syntenic to human chromosome 15q.
Autism is a neurodevelopmental disorder that manifests in childhood as social behavioral abnormalities, such as abnormal social interaction, impaired communication, and restricted interest or behavior. Of the known causes of autism, duplication of human chromosome 15q11-q13 is the most frequently associated cytogenetic abnormality. Chromosome 15q11-q13 is also known to include imprinting genes. In terms of neuroscience, it contains interesting genes such as Necdin, Ube3a, and a cluster of GABA(A) subunits as well as huge clusters of non-coding RNAs (small nucleolar RNAs, snoRNAs). Phenotypic analyses of mice genetically or chromosomally engineered for each gene or their clusters on a region of mouse chromosome seven syntenic to human 15q11-q13 indicate that this region may be involved in social behavior, serotonin metabolism, and weight control. Further studies using these models will provide important clues to the pathophysiology of autism. This review overviews phenotypes of mouse models of genes in 15q11-q13 and their relationships to autism.


Thromboembolic and Bleeding Risk in Atrial Fibrillation Patients with Chronic Kidney Disease: Role of Anticoagulation Therapy.
Atrial fibrillation (AF) and chronic kidney disease (CKD) are strictly related; several independent risk factors of AF are often frequent in CKD patients. AF prevalence is very common among these patients, ranging between 15% and 20% in advanced stages of CKD. Moreover, the results of several studies showed that AF patients with end stage renal disease (ESRD) have a higher mortality rate than patients with preserved renal function due to an increased incidence of stroke and an unpredicted elevated hemorrhagic risk. Direct oral anticoagulants (DOACs) are currently contraindicated in patients with ESRD and vitamin K antagonists (VKAs), remaining the only drugs allowed, although they show numerous critical issues such as a narrow therapeutic window, increased tissue calcification and an unfavorable risk/benefit ratio with low stroke prevention effect and augmented risk of major bleeding. The purpose of this review is to shed light on the applications of DOAC therapy in CKD patients, especially in ESRD patients.


Optimizing Insertion and Deletion Detection Using Next-Generation Sequencing in the Clinical Laboratory.
Detection of insertions and deletions (InDels) by short-read next-generation sequencing (NGS) technology can be challenging because of frequent misaligned reads. A systematic analysis of short InDels (1 to 30 bases) and fms-related receptor tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs; 6 to 183 bases) from 46 clinical cases of solid or hematologic malignancy processed with a clinical NGS assay identified misaligned reads in every case, ranging from 3% to 100% of reads with the InDel showing mismapped bases. Mismaps also increased with InDel size. As a consequence, the clinical NGS bioinformatics pipeline undercalled the variant allele frequency by 1% to 84%, incorrectly called simultaneous single-base substitutions along with InDels, or did not report an FLT3 ITD that had been detected by capillary electrophoresis. To improve the ability of the pipeline to better detect and quantify InDels, we utilized a software program called Assembly-Based ReAligner (ABRA2) to more accurately remap reads. ABRA2 was able to correct 41% to 100% of the reads with mismapped bases and led to absolute increases in the variant allele frequency from 1% to 61% along with correction of all of the single-base substitutions except for two cases. ABRA2 could also detect multiple FLT3 ITD clones except for one 183-base ITD. Our analysis has found that ABRA2 performs well on short InDels as well as FLT3 ITDs that are <100 bases.


The transferability of information and communication technology skills from university to the workplace: a qualitative descriptive study.
This paper presents the findings from a study that explored whether the information and communication technology (ICT) skills nurses acquired at university are relevant and transferable to contemporary practice environments. Whilst universities have attempted to integrate information and communication technology into nursing curricula it is not known whether the skills developed for educational purposes are relevant or transferable to clinical contexts. A qualitative descriptive study was used to explore the perspectives of a small group of new graduate nurses working in a regional/semi-metropolitan healthcare facility in New South Wales, Australia. Semi-structured interviews were used and the data thematically analysed. The themes that emerged from the study are presented in accordance with the conceptual framework and structured under the three headings of pre-transfer, transition and post-transfer. The transferability of information and communication technology skills from university to the workplace is impacted by a range of educational, individual, organisational and contextual factors. Access to adequate ICT and the necessary training opportunities influences new graduates' work satisfaction and their future employment decisions. The ability to effectively use information and communication technology was viewed as essential to the provision of quality patient care.


Removal of nitrogen from secondary effluent of a petrochemical industrial park by a hybrid biofilm-carrier reactor with one-stage ANAMMOX.
A laboratory study was undertaken to explore the capability of one-stage ANAMMOX in a hybrid biofilm-carrier reactor (HBCR) fed with petrochemical wastewater. Under favorable operating conditions in continuous-flow operations (at the dissolved oxygen level of 0.5-1.0 mg L(-1)), the average total nitrogen (TN) removal efficiency reached 62-67% and approximately 90% of TN can be removed by ANAMMOX. In batch operations of the hybrid biofilm-carrier reactor (without adding carbon substrate), the specific TN removal rate of the reactor in which both Kaldnes and nonwoven carriers were kept was two-fold higher than that of the reactor in which only nonwoven carriers were kept. This indicated that the microbial activity of thinner biofilms (Kaldnes carriers) was remarkably higher than that of thicker biofilms (nonwoven carriers). Finally, based on the 16S rRNA clone library, a cluster of ANAMMOX Candidatus Kuenenia stuttgartiensis was identified.


Restriction enzyme digestions identify discrete domains in the chromatin around the promoter of the mouse alpha 2(I) collagen gene.
We have examined the chromatin structure around the +1 transcriptional start site of the mouse alpha 2(I) collagen gene by studying the accessibility of DNA to several restriction enzymes as well as to DNase I. In NIH 3T3 cells, which express high levels of alpha 2(I) collagen mRNA, we detect a DNase I-hypersensitive site from -240 to +110 relative to the start site of transcription at +1. By digesting chromatin with restriction enzymes, which cleave naked DNA at multiple sites within the -2000 to +1000 region, a considerably more complex picture was revealed. DNA sequences upstream of around -550 and downstream of +150 are much less accessible to restriction enzymes than the region between these sites and are, therefore, probably packaged in a more compact conformation. The region from around -550 to -240 although not within the DNase I-hypersensitive domain is nevertheless accessible to restriction enzymes and, therefore, presumably in a relatively "open" conformation. In addition, beginning 5' to -100 there is a gradual decrease in restriction enzyme accessibility as one approaches +150. Of particular interest is the finding that although sites at +65 and +126 are relatively accessible, a HinfI site at +113 is resistant in chromatin. In v-mos transformed NIH 3T3 cells which express alpha 2(I) collagen at much lower levels than untransformed NIH 3T3 cells, the DNase I-hypersensitive site as well as the majority of the chromatin restriction enzyme accessibility patterns are similar to those found in untransformed NIH 3T3 cells. However, a SphI site at +58 appears less accessible in the transformed cells. We also examined the chromatin of a myeloma cell line which does not synthesize alpha 2(I) collagen at detectable levels. In the nuclei of these cells the DNA of the alpha 2(I) collagen promoter is inaccessible to DNase I and to all restriction enzymes.


[Transverse myelitis in systemic lupus erythematosus].
Transverse myelitis (TM) is a rare complication in patients with systemic lupus erithematosus (SLE). We reviewed a series of our SLE patients to determine the prevalence of TM, and evaluate the clinical characteristics, medical tests, evolution and response to the treatment. Six patients with TM were identified and underwent a neurological evaluation, MRI, electrophysiologic study and were all subjected to the same treatment. A descriptive statistical study was conducted. We observed a prevalence of 0.92% in our patients with SLE. Eighty three point three per cert had antiphospholipid antibodies and/or lupus anticoagulant. The MRI confirmed the diagnosis in 5 cases. Of the 5 patients with antiphospholypid antibodies, 3 were anticoagulated or took aspirin with a good neurological outcome, leaving 2 of them without posterior complications. We found a prevalence similar to that observed in other series, around 1%. The high prevalence of antiphospholypid antibodies in these patients, with good outcome in those anticoagulated or treated with antiplatelet agents suggests an important pathogenic role in the development of TM, and emphasized the possibility of adding to the standard treatment, antiplatelet agents or anticoagulation.


A novel visible light-curing chitosan-based hydrogel membrane for guided tissue regeneration.
Inflammation and trauma destroy the tooth-supporting tissue, leading to the loss of oral function and the difficulty of denture restoration. Guided tissue regeneration (GTR) is a technique based on a barrier membrane designed to restrict soft tissue invasion and maintain the space for bone regeneration. This study examined a new formulation to prepare methacrylated carboxymethyl chitosan (CMCS-MA) hydrogel as a barrier membrane that could be crosslinked under visible-light irradiation. This new CMCS-MA hydrogel showed fast light-curing, good biocompatibility, and could be degraded by lysozyme. Further, the physicochemical property, cytotoxicity and antibacterial activity of the CMCS-MA hydrogels can be adjusted by varying the degree of substitution of methacrylic acid (DS) in a certain range. Thus, the biocompatible and biodegradable CMCS-MA hydrogels may have a promising application in periodontal tissue regeneration with convenience and flexibility.


Recognition of the inherently unstable H2A nucleosome by Swc2 is a major determinant for unidirectional H2A.Z exchange.
The multisubunit chromatin remodeler SWR1/SRCAP/p400 replaces the nucleosomal H2A-H2B dimer with the free-form H2A.Z-H2B dimer, but the mechanism governing the unidirectional H2A-to-H2A.Z exchange remains elusive. Here, we perform single-molecule force spectroscopy to dissect the disassembly/reassembly processes of the H2A nucleosome and H2A.Z nucleosome. We find that the N-terminal 1-135 residues of yeast SWR1 complex protein 2 (previously termed Swc2-Z) facilitate the disassembly of nucleosomes containing H2A but not H2A.Z. The Swc2-mediated nucleosome disassembly/reassembly requires the inherently unstable H2A nucleosome, whose instability is conferred by three H2A α2-helical residues, Gly47, Pro49, and Ile63, as they selectively weaken the structural rigidity of the H2A-H2B dimer. It also requires Swc2-ZN (residues 1-37) that directly anchors to the H2A nucleosome and functions in the SWR1-catalyzed H2A.Z replacement in vitro and yeast H2A.Z deposition in vivo. Our findings provide mechanistic insights into how the SWR1 complex discriminates between the H2A nucleosome and H2A.Z nucleosome, establishing a simple paradigm for the governance of unidirectional H2A.Z exchange.


Investigation of antimicrobial activity of photothermal therapeutic gold/copper sulfide core/shell nanoparticles to bacterial spores and cells.
Au/CuS core/shell nanoparticles (NPs) were designed as a new type of transducer agent for photothermal therapy (PTT), with attractive features of easy preparation, low cost and small size for targeting. This paper studied for the first time the intrinsic antimicrobial activity of Au/CuS NPs to B. anthracis spores and cells in addition to its PTT effect. It was found that Au/CuS NPs were highly efficient in inactivating B. anthracis cells, but not effective to the spores. Treatment with NPs at ~0.83 μM for 30 min achieved a 7 log reduction in viable cells. The antimicrobial effect was both NPs concentration and treatment time dependent. SEM imaging and the efflux of DNA test demonstrated the damage of cell membrane after NPs treatment, yet further research is necessary to fully understand the precise inactivation mechanism. The Au/CuS NPs had strong antimicrobial activity to B. anthracis cells, which showed a great potential to be an effective antimicrobial agent to bacterial cells.


Lipids, aggression, suicidality and impulsivity in drug-naïve/drug-free patients of schizophrenia.
Present study aimed at determining lipid profiles in acutely symptomatic drug-naïve/drug-free patients of schizophrenia, comparing them with healthy controls and exploring relationships between various lipid fractions, aggression, suicidality and impulsivity in this population. This was a cross-sectional hospital-based study, comparing patients with schizophrenia (M=46, F=14; mean age 32.40±6.6 years; 48 drug-free for 10.50±9.2 weeks) with 60 age-sex matched healthy controls. Upon recruitment, fasting venous blood samples of all subjects were analysed for total cholesterol, HDL, LDL, VLDL and TG levels, and patients were rated on PANSS for symptom severity, Modified Overt Aggression Scale for aggression, Impulsivity Rating Scale for impulsivity and Scale for Suicide Ideation for suicidality. The socio-demographic characteristics of the patients were comparable to controls. In patients, total cholesterol, HDL and LDL levels were found to be significantly lower (p<0.01) than the control group. When explored further in patients, lower total cholesterol and LDL levels showed significant negative correlations with scores on impulsivity (p<0.01) and suicidality (p<0.05); and TG level showed a negative correlation with impulsivity (p<0.05). This study adds to a growing literature on a complex relationship between lipid fractions and impulsivity, suicidality and aggression in schizophrenia; providing interesting insights into the biochemical basis of human behaviour and confirming these in a developing-world population. The implications are many, including a need to review judiciously the promotion of weight loss and cholesterol reduction programmes in constitutionally vulnerable population, at least during their acutely-symptomatic states.


Absence of the sixth component of complement in a patient with repeated episodes of meningococcal meningitis.
A previously healthy 6-year-old boy who presented with meningococcal meningitis responded favorably to ampicillin, but suffered two and possibly three repeat attacks in the ensuing month. No abnormality of the otolarynx, skin, or neuroskeleton was found. The infecting strain, Neisseria meningitidis, Group Y, Type IV, was sensitive to the therapeutic agents used, and antibiotic levels were adequate. Serum bactericidal antibody titers against autologous meningococci were high. Serum complement hemolytic bactericidal activities, however, were entirely lacking, and this was attributable to a complete deficiency of C6. Measurements of the remaining complement components, C-dependent chemotaxis and opsonization, neutrophil function, specific immunity, and the coagulation system, were normal. The parents had half-normal C6 levels. Recurrence of meningitis in this patient supports the concept that complement plays a role in resistance to certain microorganisms and emphasizes the need for complete evaluation of the complement system in individuals with unexplained repeated infections.


[Proton isoshielding curves of several nucleic acid intercalating agents].
Intermolecular nuclear shielding values for protons, due to the ring-current effect, are computed for a plane parallel to and 3.4 A above the phenoxazone ring of actinomycin, ethidium, proflavin and quinacrine.


Breakdown of bulk-projected isotropy in surface electronic states of topological Kondo insulator SmB6(001).
The topology and spin-orbital polarization of two-dimensional (2D) surface electronic states have been extensively studied in this decade. One major interest in them is their close relationship with the parities of the bulk (3D) electronic states. In this context, the surface is often regarded as a simple truncation of the bulk crystal. Here we show breakdown of the bulk-related in-plane rotation symmetry in the topological surface states (TSSs) of the Kondo insulator SmB6. Angle-resolved photoelectron spectroscopy (ARPES) performed on the vicinal SmB6(001)-p(2 × 2) surface showed that TSSs are anisotropic and that the Fermi contour lacks the fourfold rotation symmetry maintained in the bulk. This result emphasizes the important role of the surface atomic structure even in TSSs. Moreover, it suggests that the engineering of surface atomic structure could provide a new pathway to tailor various properties among TSSs, such as anisotropic surface conductivity, nesting of surface Fermi contours, or the number and position of van Hove singularities in 2D reciprocal space.


Factors influencing practitioners' who do not participate in ethically complex, legally available care: scoping review.
Evolving medical technology, advancing biomedical and drug research, and changing laws and legislation impact patients' healthcare options and influence healthcare practitioners' (HCPs') practices. Conscientious objection policy confusion and variability can arise as it may occasionally be unclear what underpins non-participation. Our objective was to identify, analyze, and synthesize the factors that influenced HCPs who did not participate in ethically complex, legally available healthcare. We used Arksey and O'Malley's framework while considering Levac et al.'s enhancements, and qualitatively synthesized the evidence. We searched Medline, CINAHL, JSTOR, EMBASE, PsychINFO, Sociological Abstracts, and ProQuest Dissertations and Theses Global from January 1, 1998, to January 15, 2020, and reviewed the references of the final articles. We included articles written in English that discussed the factors that influenced physicians and registered nurses (RNs) who did not participate in end-of-life (EOL), reproductive technology and health, genetic testing, and organ or tissue donation healthcare areas. Using Covidence, we conducted title and abstract screening, followed by full-text screening against our eligibility criteria. We extracted the article's data into a spreadsheet, analyzed the articles, and completed a qualitative content analysis using NVivo12. We identified 10,664 articles through the search, and after the screening, 16 articles were included. The articles sampled RNs (n = 5) and physicians (n = 11) and encompassed qualitative (n = 7), quantitative (n = 7), and mixed (n = 2) methodologies. The care areas included reproductive technology and health (n = 11), EOL (n = 3), organ procurement (n = 1), and genetic testing (n = 1). One article included two care areas; EOL and reproductive health. The themed factors that influenced HCPs who did not participate in healthcare were: (1) HCPs' characteristics, (2) personal beliefs, (3) professional ethos, 4) emotional labour considerations, and (5) system and clinical practice considerations. The factors that influenced HCPs' who did not participate in ethically complex, legally available care are diverse. There is a need to recognize conscientious objection to healthcare as a separate construct from non-participation in healthcare for reasons other than conscience. Understanding these separate constructs will support HCPs' specific to the underlying factors influencing their practice participation.


Synthesis and chemotactic activity of the fMLP analog HCO-Hmb-Leu-Phe-OMe.
The new fMLP analog HCO-Hmb-Leu-Phe-OMe (1), containing (S)-2-hydroxy-4-(methylthio)butyric acid (Hmb) in place of L-methionine at the N-terminal position, has been synthesized and fully characterized. The peptide 1 has been designed in order to improve the understanding of the role exerted by the formamido group in the binding interaction with the formylpeptide chemotactic receptors. Chemotaxis, superoxide anion production, and lysozyme release have been measured for both 1 and its deformylated analog Hmb-Leu-Phe-OMe 2. Results indicate that a strong hydrogen bond of the OH....O = C type may complement a weak H-bonding interaction involving the formylic proton as H-bond donor.


Association of body mass index with clinical outcomes for in-hospital cardiac arrest adult patients following extracorporeal cardiopulmonary resuscitation.
Obesity might be associated with disturbance of cannulation in situation of extracorporeal cardiopulmonary resuscitation (ECPR). However, limited data are available on obesity in the setting of ECPR. Therefore, we investigated the association between body mass index (BMI) and clinical outcome in patients underwent ECPR. From January 2004 to December 2013, in-hospital cardiac arrest patients who had ECPR were enrolled from a single-center registry. We divided patients into four group according to BMI defined with the WHO classification (underweight, BMI < 18.5, n = 14; normal weight, BMI = 18.5-24.9, n = 118; overweight, BMI = 25.0-29.9, n = 53; obese, BMI ≥ 30, n = 15). The primary outcome was survival to hospital discharge. Analysis was carried out for a total of 200 adult patients (39.5% females). Their median BMI was 23.20 (interquartile range, 20.93-25.80). The rate of survival to hospital discharge was 31.0%. There was no significant difference in survival to hospital discharge among the four groups (underweight, 35.7%; normal, 31.4%; overweight, 30.2%; obese, 26.7%, p = 0.958). Neurologic outcomes (p = 0.85) and procedural complications (p = 0.40) were not significantly different among the four groups either. SOFA score, initial arrest rhythm, and CPR to extracorporeal membrane oxygenation (ECMO) pump on time were significant predictors for survival to discharge, but not BMI. BMI was not associated with in-hospital mortality who underwent ECPR. Neurologic outcomes at discharge or procedural complications following ECPR were not related with BMI either.


Predictors of acute rejection after lung transplantation.
Acute rejection (AR) after lung transplantation (LTx) impacts survival and quality of life. The objective of this study, therefore, was to identify risk factors for AR after LTx, focusing on donor- and recipient-specific factors, operative variables, and immunologic issues, including pretransplant panel-reactive antibody (PRA) levels, and donor-recipient human leukocyte antigen (HLA) mismatch. From March 1996 to November 2007, 481 adults undergoing LTx had 3237 serial transbronchial biopsy specimens that were evaluated for perivascular rejection (grade A0 to A4). Longitudinal analysis was used to characterize the prevalence of rejection grade and influence of donor, recipient, technical, and immunologic variables. AR was highest (54%≥A1) in the first 2 months after LTx, decreased at 6 months (16%≥A1), then remained steady. Prevalence of AR at any time was dominated by donor-specific factors of young age (p<0.0001), blunt trauma (p=0.008), and nonblack race (p=0.012) and by recipient class II PRA exceeding 10% (p=0.005). AR within 2 months was associated with HLA mismatch at the DR locus (p=0.0006) and use of non-O blood-group donors (p=0.008). AR at 4 years and longer after LTx was associated with HLA mismatch at the B locus (p=0.01). Only a few recipient and operative factors were identified for AR after LTx. Moderately sensitized recipients identified by class II PRA exceeding 10% and those with HLA mismatches at the B and DR loci appear to be more susceptible to AR; however, such immunologic variations appear to be well controlled with current donor selection and immunosuppression protocols. The impact of donor-specific variables on AR is surprisingly strong and warrants closer inspection.


Elevated responses to constant facial emotions in different faces in the human amygdala: an fMRI study of facial identity and expression.
Human faces provide important signals in social interactions by inferring two main types of information, individual identity and emotional expression. The ability to readily assess both, the variability and consistency among emotional expressions in different individuals, is central to one's own interpretation of the imminent environment. A factorial design was used to systematically test the interaction of either constant or variable emotional expressions with constant or variable facial identities in areas involved in face processing using functional magnetic resonance imaging. Previous studies suggest a predominant role of the amygdala in the assessment of emotional variability. Here we extend this view by showing that this structure activated to faces with changing identities that display constant emotional expressions. Within this condition, amygdala activation was dependent on the type and intensity of displayed emotion, with significant responses to fearful expressions and, to a lesser extent so to neutral and happy expressions. In contrast, the lateral fusiform gyrus showed a binary pattern of increased activation to changing stimulus features while it was also differentially responsive to the intensity of displayed emotion when processing different facial identities. These results suggest that the amygdala might serve to detect constant facial emotions in different individuals, complementing its established role for detecting emotional variability.


A Prospective Study Comparing Leukocyte-Poor Platelet-Rich Plasma Combined with Hyaluronic Acid and Autologous Microfragmented Adipose Tissue in Patients with Early Knee Osteoarthritis.
The objective of this study was to compare the clinical efficacy of repeated doses of leucocyte-poor platelet-rich plasma (LP-PRP) plus hyaluronic acid (HA) to a single dose of autologous microfragmented adipose tissue (AMAT) injections in patients with early osteoarthritis (OA) symptoms. Eighty knees in 50 patients (mean age: 61.3 years) were randomly allocated into two equal groups in a nonblinded design and prospectively followed for 12 months. Group 1 received three intra-articular injections (1 month apart) using autologous LP-PRP+HA. Group 2 received a single dose of AMAT injection. Outcomes were measured by PROMs Tegner, Marx, visual analog scale, and Knee Injury and Osteoarthritis Outcome Score (KOOS) at 6 and 12 months. Both groups had significant clinical and functional improvement at 6 and 12 months. The differences between groups were statistically significant in Tegner score and KOOS symptoms (both P < 0.05) at 6 months in group 2. The test with statistically significant differences (P < 0.05) at 12 months was Tegner (P < 0.001), with group 2 having a higher median than group 1. LP-PRP+HA and AMAT lead to clinical and functional improvement at 6 and 12 months. AMAT showed better clinical results in Tegner and KOOS symptoms at 6 months and Tegner at 12 months. Understanding which therapy offers the most benefits with the least risk can significantly improve the quality of life for millions of people affected by OA. Long-term randomized controlled studies are needed to verify differences in efficacy.


Changes in the rat thymus cytoarchitectonics during repeated exposure to hypergravitation.
Comparative study of the structural and functional changes in rat thymus after 5-day and repeated 5-day exposure to hypergravitation (2g) showed less pronounced changes after repeated exposure. Proliferative potential of thymic lymphocytes was higher and their loss (death) was lower after repeated exposure to hypergravitation, which attested to better adaptation of the thymus during repeated prolonged exposure to hypergravitation than after single exposure of the same intensity and duration. Our findings suggest the possibility of the formation of gravitation memory in thymic lymphocytes during repeated long-term exposure to hypergravitation.


Development of a real-time PCR assay using SYBR Green chemistry for monitoring Marek's disease virus genome load in feather tips.
Feather follicles of birds infected with Marek's disease virus (MDV) serve as the sole source of infectious virus particles. The present study was aimed at developing a SYBR Green real-time PCR assay to detect and quantify MDV loads in feather tips targeting meq gene of the virus. The assay had a dynamic range of 8 logs, mean inter- and intra-assay coefficient variation (CV) of <5% and minimum detection limit of 15 MDV genome copies when plasmid DNA was used as the template. The sensitivity of the assay was compared with that of the conventional PCR technique and found to be 2.5-10 times more sensitive than the conventional PCR technique. The assay was validated using feather tip DNA preparations derived from chickens infected with 250 plaque forming units (PFU) of RB1B strain of MDV and sampled on days 7, 14, 21 and 28 post-infection (p.i.) along with uninfected chickens. MDV genome was quantifiable in feather tips of infected birds by day 7 p.i. and the number of MDV copies peaked by day 14 p.i., but then gradually decreased by day 28. This reliable real-time PCR assay may be used for monitoring MDV genome loads in tissues of experimentally or naturally infected birds.


Epstein-Barr-virus-encoded LMP2A induces primary epithelial cell migration and invasion: possible role in nasopharyngeal carcinoma metastasis.
Nonkeratinizing nasopharyngeal carcinomas (NPC) are >95% associated with the expression of the Epstein-Barr virus (EBV) LMP2A latent protein. However, the role of EBV, in particular, LMP2A, in tumor progression is not well understood. Using Affymetrix chips and a pattern-matching computational technique (neighborhood analysis), we show that the level of LMP2A expression in NPC biopsy samples correlates with that of a cellular protein, integrin-alpha-6 (ITGalpha6), that is associated with cellular migration in vitro and metastasis in vivo. We have recently developed a primary epithelial model from tonsil tissue to study EBV infection in epithelial cells. Here we report that LMP2A expression in primary tonsil epithelial cells causes them to become migratory and invasive, that ITGalpha6 RNA levels are up-regulated in epithelial cells expressing LMP2, and that ITGalpha6 protein levels are increased in the migrating cells. Blocking antibodies against ITGalpha6 abrogated LMP2-induced invasion through Matrigel by primary epithelial cells. Our results provide a link between LMP2A expression, ITGalpha6 expression, epithelial cell migration, and NPC metastasis and suggest that EBV infection may contribute to the high incidence of metastasis in NPC progression.


Serum chromogranin A levels are associated with the SYNTAX score in coronary artery disease.
In this article, we investigated the association of chromogranin A with coronary artery disease. Biochemical parameters and chromogranin A levels obtained from peripheral blood samples during coronary angiography were analyzed in 90 patients. Patients were classified into two groups, namely, SYNergy between PCI with TAXUS and Cardiac Surgery score ≥1 (n=45) and SYNergy between PCI with TAXUS and Cardiac Surgery score=0 (n=45). This is a cross-sectional, prospective study. Serum chromogranin A levels were significantly higher in the group with SYNergy between PCI with TAXUS and Cardiac Surgery score ≥1 compared to the group with SYNergy between PCI with TAXUS and Cardiac Surgery score=0 (1381.5±418.9 ng/mL and 1121.2±290.7 ng/mL, respectively; p=0.002). Serum chromogranin A levels were correlated with SYNergy between PCI with TAXUS and Cardiac Surgery score (r=0.556, p<0.04). ROC analysis showed that the area under the curve for serum chromogranin A levels was 0.687 (p=0.007), and the best cutoff value of 1,131 ng/mL had a sensitivity of 67% and a specificity of 65% for the prediction of coronary artery disease. Serum chromogranin A levels were increased in coronary artery disease patients with SYNergy between PCI with TAXUS and Cardiac Surgery score ≥1. Increasing serum chromogranin A levels are proportional to the SYNergy between PCI with TAXUS and Cardiac Surgery score.


Accelerated repair of cortical bone defects using a synthetic extracellular matrix to deliver human demineralized bone matrix.
Injectable hydrogel and porous sponge formulations of Carbylan-GSX, a crosslinked synthetic extracellular matrix (ECM), were used to deliver human demineralized bone matrix (DBM) in a rat femoral defect model. A cortical, full-thickness 5-mm defect was created in two femurs of each rat. Six rats were assigned to each of five experimental groups (thus, 12 defects per group). The defects were either untreated or filled with Carbylan-GSX hydrogel or sponges with or without 20% (w/v) DBM. Radiographs were obtained on day 1 and at weeks 2, 4, 6, and 8 postsurgery of each femur. Animals were sacrificed at week 8 postsurgery and each femur was fixed, embedded, sectioned, and processed for Masson's Trichrome staining. The bone defects were measured from radiographs and the fraction of bone healing was calculated. The average fractions of bone healing for each group were statistically different among all groups, and all treatment groups were significantly better than the control group. The Carbylan-GSX sponge with DBM was superior to the sponge without DBM and to the hydrogel with DBM. Histology showed that defects treated with the Carbylan-GSX sponge plus DBM were completely filled with newly generated bone tissue with a thickness comparable to native bone. Carbylan-GSX sponge was an optimal delivery vehicle for human DBM to accelerate bone healing.


Varied Presentations of Acute Glomerulonephritis in Children: Single centre experience from a developing country.
The objective of this prospective study, carried out at Manipal Teaching Hospital, Pokhara, was to document the various clinical presentations of children with acute glomerulonephritis and compare them with the available biological parameters in Western Nepal. Clinical and laboratory parameters of children with oedema and microscopic/macroscopic haematuria. For seven years (2000-2007), 92 cases of children were clinically diagnosed with acute glomerulonephritis (AGN). Other clinical and laboratory anaylses were also eventful. The present study highlights the varied presentations of AGN, atypical presentations or complications of glomerulonephritis being more common than the classical presentation in the Western Region of Nepal.


Inhibition of dual leucine zipper kinase prevents chemotherapy-induced peripheral neuropathy and cognitive impairments.
Chemotherapy-induced peripheral neuropathy (CIPN) and chemotherapy-induced cognitive impairments (CICI) are common, often severe neurotoxic side effects of cancer treatment that greatly reduce quality of life of cancer patients and survivors. Currently, there are no Food and Drug Administration-approved agents for the prevention or curative treatment of CIPN or CICI. The dual leucine zipper kinase (DLK) is a key mediator of axonal degeneration that is localized to axons and coordinates the neuronal response to injury. We developed a novel brain-penetrant DLK inhibitor, IACS'8287, which demonstrates potent and highly selective inhibition of DLK in vitro and in vivo. Coadministration of IACS'8287 with the platinum derivative cisplatin prevents mechanical allodynia, loss of intraepidermal nerve fibers in the hind paws, cognitive deficits, and impairments in brain connectivity in mice, all without interfering with the antitumor activity of cisplatin. The protective effects of IACS'8287 are associated with preservation of mitochondrial function in dorsal root ganglion neurons and in brain synaptosomes. In addition, RNA sequencing analysis of dorsal root ganglia reveals modulation of genes involved in neuronal activity and markers for immune cell infiltration by DLK inhibition. These data indicate that CIPN and CICI require DLK signaling in mice, and DLK inhibitors could become an attractive treatment in the clinic when coadministered with cisplatin, and potentially other chemotherapeutic agents, to prevent neurotoxicities as a result of cancer treatment.


A conserved small RNA promotes discoordinate expression of the glmUS operon mRNA to activate GlmS synthesis.
Many bacterial genes of related function are organized in operons and transcribed as polycistronic mRNAs to ensure the coordinate expression of the individual cistrons. Post-transcriptional modulation of such mRNAs can alter the expression of downstream cistrons, resulting in discoordinate protein synthesis from an operon mRNA. Several factors, including small non-coding RNAs (sRNAs), have been described that act collectively as repressors within polycistronic mRNAs. We describe the first case of discoordinated operon expression in which a downstream cistron is activated at the post-transcriptional level. We report that GlmY sRNA activates GlmS synthesis from the Escherichia coli glmUS mRNA without altering GlmU expression. The sRNA is shown to be structurally and functionally conserved in diverse enterobacteria; its transcription may be controlled by the alternative sigma factor, sigma(54). Our data suggest that Gram-negative bacteria evolved a mechanism of glmS riboregulation that is distinct from the glmS riboswitch mechanism of Gram-positive bacteria.


Integrated care for older populations and its implementation facilitators and barriers: A rapid scoping review.
Inform health system improvements by summarizing components of integrated care in older populations. Identify key implementation barriers and facilitators. A scoping review was undertaken for evidence from MEDLINE, the Cochrane Library, organizational websites and internet searches. Eligible publications included reviews, reports, individual studies and policy documents published from 2005 to February 2017. Initial eligible documents were reviews or reports concerning integrated care approaches in older/frail populations. Other documents were later sourced to identify and contextualize implementation issues. Study findings and implementation barriers and facilitators were charted and thematically synthesized. Thematic synthesis using 30 publications identified 8 important components for integrated care in elderly and frail populations: (i) care continuity/transitions; (ii) enabling policies/governance; (iii) shared values/goals; (iv) person-centred care; (v) multi-/inter-disciplinary services; (vi) effective communication; (vii) case management; (viii) needs assessments for care and discharge planning. Intervention outcomes and implementation issues (barriers or facilitators) tend to depend heavily on the context and programme objectives. Implementation issues in four main areas were observed: (i) Macro-level contextual factors; (ii) Miso-level system organization (funding, leadership, service structure and culture); (iii) Miso-level intervention organization (characteristics, resources and credibility) and (iv) Micro-level factors (shared values, engagement and communication). Improving integration in care requires many components. However, local barriers and facilitators need to be considered. Changes are expected to occur slowly and are more likely to be successful where elements of integrated care are well incorporated into local settings.


High-molecular weight Aβ oligomers and protofibrils are the predominant Aβ species in the native soluble protein fraction of the AD brain.
Alzheimer's disease (AD) is characterized by the aggregation and deposition of amyloid β protein (Aβ) in the brain. Soluble Aβ oligomers are thought to be toxic. To investigate the predominant species of Aβ protein that may play a role in AD pathogenesis, we performed biochemical analysis of AD and control brains. Sucrose buffer-soluble brain lysates were characterized in native form using blue native (BN)-PAGE and also in denatured form using SDS-PAGE followed by Western blot analysis. BN-PAGE analysis revealed a high-molecular weight smear (>1000 kD) of Aβ(42) -positive material in the AD brain, whereas low-molecular weight and monomeric Aβ species were not detected. SDS-PAGE analysis, on the other hand, allowed the detection of prominent Aβ monomer and dimer bands in AD cases but not in controls. Immunoelectron microscopy of immunoprecipitated oligomers and protofibrils/fibrils showed spherical and protofibrillar Aβ-positive material, thereby confirming the presence of high-molecular weight Aβ (hiMWAβ) aggregates in the AD brain. In vitro analysis of synthetic Aβ(40) - and Aβ(42) preparations revealed Aβ fibrils, protofibrils, and hiMWAβ oligomers that were detectable at the electron microscopic level and after BN-PAGE. Further, BN-PAGE analysis exhibited a monomer band and less prominent low-molecular weight Aβ (loMWAβ) oligomers. In contrast, SDS-PAGE showed large amounts of loMWAβ but no hiMWAβ(40) and strikingly reduced levels of hiMWAβ(42) . These results indicate that hiMWAβ aggregates, particularly Aβ(42) species, are most prevalent in the soluble fraction of the AD brain. Thus, soluble hiMWAβ aggregates may play an important role in the pathogenesis of AD either independently or as a reservoir for release of loMWAβ oligomers.


The crystal structures of three disordered 2-substituted benzimidazole esters.
The crystal structures of three benzimidazole esters containing aryl or heterocyclic substituents at position 2 are reported, and all three exhibit disorder of mol-ecular entities. In ethyl 1-methyl-2-[4-(prop-2-yn-oxy)phen-yl]-1H-benzimidazole-5-carboxyl-ate, C20H18N2O3, (I), the prop-2-yn-1-oxyphenyl unit is disordered over two sets of atomic sites having effectively equal occupancies, 0.506 (5) and 0.494 (5). The propyl substituent in ethyl 1-propyl-2-(pyren-1-yl)-1H-benzimidazole-5-carboxyl-ate, C29H24N2O2, (II), is disordered over two sets of atomic sites having occupancies 0.601 (8) and 0.399 (8), and the ester unit in ethyl 1-methyl-2-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)-1H-benzimidazole-5-carboxyl-ate, C21H19ClN4O2 (III), is disordered over two sets of atomic sites having occupancies 0.645 (7) and 0.355 (7). In each of the C-H⋯π(arene) hydrogen bonds in (I), the donor and acceptor form parts of different disorder components, so that no continuous aggregation is possible. The mol-ecules of (II) are linked by a single C-H⋯O hydrogen bond into C(10) chains, which are linked into sheets by a π-π stacking inter-action, whereas those of (III) are just linked into C(13) chains, again by a single C-H⋯O hydrogen bond. Comparisons are made with the structures of some related compounds.


Access to preventive health care: is method of payment a barrier for immigrant Hispanic women?
This study describes the payment category of 397 low-income Hispanic women and the relationship to compliance with family planning visits the first year postbirth. Only one-fourth of the women returned for the one-year family planning visit, when they would have received well-woman care. Pay category was not a factor in identifying those who returned. Health system barriers, patient cultural beliefs, and life circumstance may explain why women enter and then leave apparently seamless systems of care. To increase preventive care, more study is needed of interventions that build on women's existing cultural prescriptions for health behavior by health professionals who portray postbirth checks as wellness checks.


Familial aggregation and shared genetic loading for major psychiatric disorders and type 2 diabetes.
Psychiatric disorders, such as schizophrenia (SCZ), major depressive disorder (MDD) and bipolar disorder (BPD), are highly comorbid with type 2 diabetes. However, the mechanisms underlying such comorbidity are understudied. This study explored the familial aggregation of common psychiatric disorders and type 2 diabetes by testing family history association, and investigated the shared genetic loading between them by testing the polygenic risk score (PRS) association. A total of 105,184 participants were recruited from the Taiwan Biobank, and genome-wide genotyping data were available for 95,238 participants. The Psychiatric Genomics Consortium-derived PRS for SCZ, MDD and BPD was calculated. Logistic regression was used to estimate the OR with CIs between a family history of SCZ/MDD/BPD and a family history of type 2 diabetes, and between the PRS and the risk of type 2 diabetes. A family history of type 2 diabetes was associated with a family history of SCZ (OR 1.23, 95% CI 1.08, 1.40), MDD (OR 1.19, 95% CI 1.13, 1.26) and BPD (OR 1.26, 95% CI 1.15, 1.39). Compared with paternal type 2 diabetes, maternal type 2 diabetes was associated with a higher risk of a family history of SCZ. SCZ PRS was negatively associated with type 2 diabetes in women (OR 0.92, 95% CI 0.88, 0.97), but not in men; the effect of SCZ PRS reduced after adjusting for BMI. MDD PRS was positively associated with type 2 diabetes (OR 1.04, 95% CI 1.00, 1.07); the effect of MDD PRS reduced after adjusting for BMI or smoking. BPD PRS was not associated with type 2 diabetes. The comorbidity of type 2 diabetes with psychiatric disorders may be explained by shared familial factors. The shared polygenic loading between MDD and type 2 diabetes implies not only pleiotropy but also a shared genetic aetiology for the mechanism behind the comorbidity. The negative correlation between polygenic loading for SCZ and type 2 diabetes implies the role of environmental factors.


Lymphocyte Subsets in HIV-Exposed Uninfected Infants: The Impact of Neonatal Postexposure Prophylaxis With Zidovudine.
HIV-exposed, uninfected (HEU) infants receiving neonatal postexposure prophylaxis with zidovudine showed nonsignificant trends of lower CD4 and CD8 T cells as well as CD19 B cells than those who did not, suggesting toxicity that might impact the overall health of HEU children.


The zebrafish model system for dyslipidemia and atherosclerosis research: Focus on environmental/exposome factors and genetic mechanisms.
Dyslipidemias and atherosclerosis play a pivotal role in cardiovascular risk and disease. Although some pathophysiological mechanisms underlying these conditions have been unveiled, several knowledge gaps still remain. Experimental models, both in vitro and in vivo, have been instrumental to our better understanding of such complex processes. The latter have often been based on rodent species, either wild-type or, in several instances, genetically modified. In this context, the zebrafish may represent an additional very useful in vivo experimental model for dyslipidemia and atherosclerosis. Interestingly, the lipid metabolism of zebrafish shares several features with that present in humans, recapitulating some molecular features and pathophysiological aspects in a better way than that of rodents. The zebrafish model may be of help to address questions related to exposome factors as well as to genetic features, aiming to dissect selected aspects of the more complex scenario observed in humans. Indeed, exposome-related dyslipidemia/atherosclerosis research in zebrafish may target different scientific questions, related to nutrition, microbiota, temperature, light exposure at the larval stage, exposure to chemicals and epigenetic consequences of such external factors. Addressing genetic features related to dyslipidemia/atherosclerosis using the zebrafish model is already a reality and active research is now ongoing in this promising area. Novel technologies (gene and genome editing) may help to identify new candidate genes involved in dyslipidemia and dyslipidemia-related diseases. Based on these considerations, the zebrafish experimental model appears highly suitable for the study of exposome factors, genes and molecules involved in the development of atherosclerosis-related disease as well as for the validation of novel potential treatment options.


Characterization of type II phosphatidylinositol 4-kinase isoforms reveals association of the enzymes with endosomal vesicular compartments.
Phosphorylation of phosphatidylinositol (PI) to PI 4-phosphate is one of the key reactions in the production of phosphoinositides, lipid regulators of several cellular functions. This reaction is catalyzed by multiple enzymes that belong either to the type II or the type III family of PI 4-kinases. Type III enzymes are structurally similar to PI 3-kinases and are sensitive to PI 3-kinase inhibitors. In contrast, the recent cloning of the first type II PI 4-kinase enzyme defined a novel enzyme family. Here we characterize a new member of this family, the type IIbeta enzyme that has been identified in the NCBI data base based on its homology to the first-cloned type IIalpha enzyme. The type IIbeta enzyme has a primary transcript size of approximately 3.8 kb and shows wide tissue distribution. It contains an open reading frame of 1.4 kb, encoding a protein of approximately 54 kDa. Sequence comparison reveals a high degree of similarity to the type IIalpha enzyme within the C-terminal catalytic domain but significantly lower homology within the N-terminal region. Expression of both enzyme yields increased PI 4-kinase activity that is associated with the microsomal membrane fractions and is significantly lower for the type IIbeta than the type IIalpha form. Both enzymes use PI as their primary substrate and have no detectable activity on PI monophosphates. Epitope-tagged as well as green fluorescent protein-tagged forms of both enzymes localize primarily to intracellular membranes and show prominent co-localization with early endosomes and recycling endosomes but not with the Golgi. These compartments participate in the processing of both the transferrin receptor and the G protein-coupled AT(1A) angiotensin receptor. Our data indicate the existence of multiple forms of type II PI 4-kinase in mammalian cells and suggest that their functions are related to the endocytic pathway.


Oncologic safety of nipple skin-sparing or total skin-sparing mastectomies with immediate reconstruction.
Success with skin-sparing mastectomy (SSM) has led to the reconsideration of the necessity to remove the skin overlying the nipple-areola complex. The aim of our study was to compare complications and local recurrence in patients undergoing SSM and total skin-sparing mastectomy (TSSM) with immediate reconstruction. This IRB-approved retrospective study involved patients who underwent mastectomy with reconstruction (1998 to 2010). Patient demographics, tumor characteristics, type of surgery, cosmesis, postoperative complications, and recurrence were analyzed. The 293 patients in our study group had a total of 508 procedures: 281 TSSMs and 227 SSMs, distributed among 215 patients with bilateral procedures and 78 with unilateral operations. Mean age was 51.2 ± 10.9 years for TSSM and 53.1 ± 11.5 years for SSM. The average tumor size was 1.9 ± 1.6 cm for TSSM versus 2.1 ± 1.7 cm for the SSM group. The overall complication rate (TSSM 7.1% [20 of 281] and SSM 6.2% [14 of 227], p = 0.67) and local-regional recurrence rate (TSSM 6% [7 of 152] and SSM 5.0% [7 of 141], p = 0.89) were comparable. The TSSM rating was significantly higher (score 9.2 ± 1.1) than the SSM group (score 8.3 ± 1.9, p = 0.04). TSSM appears to be oncologically safe with superior cosmesis, affords one-step immediate reconstruction, and can be offered to patients with stages I and II breast cancer and those who have been down-staged with neoadjuvant chemotherapy.


Mutations in the fumarylacetoacetate hydrolase gene causing hereditary tyrosinemia type I: overview.
Tyrosinemia type I is an inborn error of metabolism caused by a deficiency in the last enzyme of the tyrosine catabolic pathway, fumarylacetoacetate hydrolase (FAH). The disease has been reported worldwide with varying incidence. Recently, there has been considerable progress in identifying mutations in the FAH gene. At present 26 mutations have been reported, all consisting of single base substitutions resulting in 16 amino acid replacements, one silent mutation causing a splicing defect, five nonsense codons, and four putative splicing defects. The location of these mutations is spread over the entire FAH gene, with a particular clustering between amino acid residues 230 and 250. The identification of these mutations in subpopulations and groups at high risk should help in the diagnosis of, and genetic counseling for, HT1. We describe all these 26 mutations reported so far and their implication in diagnosis and carrier detection.


Corrigendum to "Isothermal Titration Calorimetry and Surface Plasmon Resonance Analysis Using the Dynamic Approach".
[This corrects the article DOI: 10.1016/j.bbrep.2019.100712.].