Spatial distribution, accumulation and human health risk assessment of heavy metals in soil and groundwater of the Tano Basin, Ghana.
Soil serves as a vast matrix for heavy metal accumulation and subsequent redistribution to critical aspects of the environment such as groundwater. Soil pollution study is essential for sustainable human health and ecosystem protection. This study provides vital insight into the fate, accumulation, interactions, and health risk posed by heavy metals in soil and groundwater by employing geochemical accumulation index (Igeo), risk assessment models and multivariate data analysis techniques such as principal component analysis (PCA), preference ranking organisation method for enrichment evaluation (PROMETHEE) and geometrical analysis for interactive aid (GAIA). The median Igeo estimates show moderate to strong Pb accumulation levels whilst all the other metals indicate uncontaminated to moderate levels. The PCA output point to anthropogenic origin of Pb and Cd in the Tano Basin and surrounding communities. PROMETHEE-GAIA results indicate that Pb, Cd, Zn and Fe accumulated in the soil matrix may potentially leach into the groundwater resources. The carcinogenic lifetime risks posed by Pb, Cd, and Ni metals to adults are within the tolerable acceptable risk and thus do not present an immediate danger in the study area. Due to the significant toxicity, bioaccumulation and biomagnification properties of Pb and Cd in the environment, areas associated with significant anthropogenic activities require regular monitoring and evaluation in order to ensure that these metals are consistently below the regulatory limits. This study has further elucidated the subject of heavy metal pollution and is therefore expected to enhance sustainable protection of the environment and human health.


Feasibility and preliminary efficacy of a hypopressive exercise program on postmenopausal cancer survivors: A pilot study.
Cancer-related fatigue (CRF) is a common symptom during and after cancer treatment that negatively affects the patient's quality of life. Exercise is one of the most effective non-pharmacological treatments for CRF. Multimodal exercise therapy programs that include hypopressive exercises, relaxation and myofascial release may be beneficial for CRF. The aim of this pilot study was to evaluate the feasibility and efficacy of a multimodal program on CRF and lower limb functional strength in postmenopausal women diagnosed with cancer. 7 postmenopausal women (age = 55.28 years; BMI = 26.05 kg/m2) who had a cancer diagnosis participated in a supervised and progressive 55-min class once per week for 12-weeks. CRF was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Cancer Related Fatigue 12 and lower limb strength was assessed with the sit and stand test. No adverse events were reported during the training period and all participants completed the exercise protocol. There was a significant increase (p = 0.01) in lower limb functional strength (pre: 19.60 (SD = 2.19) vs post: 24.60(SD = 2.19)) with an effect size of d = 2.28 and a decrease in CRF (p = 0.245) (pre: 29.36 ± 24.42; post: 17.85 ± 14.23) with a trivial effect size (d < 0.5). These preliminary findings indicate that a supervised once per week multimodal program that includes hypopressive exercises for postmenopausal cancer survivors increased lower limb functional strength without exacerbating their CRF. These findings support further randomized trials of hypopressive training programs on patients with cancer.


Evaluation of a selective medium for Brucella isolation using natamycin.
To select an anti-fungal agent to replace cycloheximide in the media used for isolation of Brucella. One potential agent, natamycin, was evaluated using 28 Brucella isolates, 18 yeasts and 14 fungi. The material for the evaluation included 37 bovine milk samples, six bovine vaginal swabs and 45 milk samples artificially infected with Brucella. The recovery of Brucella only from the artificially-inoculated milk samples increased with the use of the medium containing natamycin instead of cycloheximide, at the same time significantly inhibiting the growth of yeasts, fungi and other bacteria. The inclusion of either anti-fungal agent allowed growth of the 28 Brucella isolates and totally prevented the growth of all 18 yeasts and 13 of the 14 fungi. Based on the results it was concluded that natamycin would be a suitable alternative to cycloheximide. Cycloheximide has become unavailable worldwide and is currently an anti-fungal constituent of the medium often used for isolation of Brucella organisms. The use of natamycin as a replacement in the formulation did not inhibit growth of Brucella and was effective at eliminating most contaminants.


The effect of combined factor XI deficiency with von Willebrand factor abnormalities on haemorrhagic diathesis.
To account for the lack of correlation between the level of factor XI (FXI) in deficient patients and haemorrhagic manifestations, we correlated the prevalence of combined FXI and von Willebrand's factor (vWF) deficiency in 212 FXI-deficient patients. Fifty-four patients had a combined FXI and vWF deficiency: 16 patients had severe and 38 patients had mild FXI deficiency. In a group of 28 patients with comparably mild FXI deficiency, 14 bleeders had significantly lower mean vWF, Ag, ristocetin cofactor and ristocetin induced platelet aggregation than 14 non-bleeders selected on the basis of comparable FXI levels. These findings suggest that the combination of FXI and vWF deficiency is common and may affect the bleeding tendency in mild FXI deficiency.


Circular dichroism study of ribonuclease A mutants containing the minimal structural requirements for dimerization and swapping.
Four residues Pro19. Leu28, Cys31 and Cys32 proved to be the minimal structural requirements in determining the dimeric structure and the N-terminal segment swapping of bovine seminal ribonuclease, BS-RNase. We analyzed the content of secondary and tertiary structures in RNase A, P-RNase A, PL-RNase A, MCAM-PLCC-RNase A and MCAM-BS-RNase, performing near and far-UV CD spectra. It results that the five proteins have very similar native conformations. Thermal denaturation at pH 5.0 of the proteins. studied by means of CD measurements. proved reversible and well represented by the two-state N<==>D transition model. Thermodynamic data are discussed in the light of the structural information available for RNase A and BS-RNase.


[The COVID-19 Pandemic as an Opportunity and Challenge for Registries in Health Services Research: Lessons Learned from the Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS)].
The Coronavirus Disease-2019 (COVID-19) pandemic has brought opportunities and challenges, especially for health services research based on routine data. In this article we will demonstrate this by presenting lessons learned from establishing the currently largest registry in Germany providing a detailed clinical dataset on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected patients: the Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS). LEOSS is based on a collaborative and integrative research approach with anonymous recruitment and collection of routine data and the early provision of data in an open science context. The only requirement for inclusion was a SARS-CoV-2 infection confirmed by virological diagnosis. Crucial strategies to successfully realize the project included the dynamic reallocation of available staff and technical resources, an early and direct involvement of data protection experts and the ethics committee as well as the decision for an iterative and dynamic process of improvement and further development. Thanks to the commitment of numerous institutions, a transsectoral and transnational network of currently 133 actively recruiting sites with 7,227 documented cases could be established (status: 18.03.2021). Tools for data exploration on the project website, as well as the partially automated provision of datasets according to use cases with varying requirements, enabled us to utilize the data collected within a short period of time. Data use and access processes were carried out for 97 proposals assigned to 27 different research areas. So far, nine articles have been published in peer-reviewed international journals. As a collaborative effort of the whole network, LEOSS developed into a large collection of clinical data on COVID-19 in Germany. Even though in other international projects, much larger data sets could be analysed to investigate specific research questions through direct access to source systems, the uniformly maintained and technically verified documentation standard with many discipline-specific details resulted in a large valuable data set with unique characteristics. The lessons learned while establishing LEOSS during the current pandemic have already created important implications for the design of future registries and for pandemic preparedness and response.


Hereditary multiple exostoses of the ribs: an unusual cause of hemothorax and pericardial effusion.
A 6-year-old girl with hereditary multiple exostoses presented with spontaneous hemothorax and pericardial effusion. Chest computed tomographic scan showed left-sided costal exostoses protruding into the left side of the chest. She underwent successful thoracoscopic resection of 3 left rib exostoses and made a full recovery. This report illustrates this rare clinical scenario and reviews the previously published reports of this complication of costal exostoses.


The rs387907171 SNP in TYRP1 is not associated with blond hair color on the Island of Bougainville.
The aims of this study are to characterize the frequency of the derived allele at rs387907171 in populations from the islands of New Britain and Bougainville in Northern Island Melanesia, to confirm its association with lighter hair color, and to refine hypotheses regarding its evolutionary history. rs387907171 was genotyped in 93 individuals from New Britain and 101 from Bougainville for whom quantitative assessments of skin and hair pigmentation were available. Combining these with existing data from other Melanesian islands we tested for differences in allele frequencies between islands and for associations with skin and hair pigmentation using ANOVA, including sex, age, and island affiliations as covariates. The derived allele at rs387907171 was observed in a single copy in the New Britain and Bougainville populations genotyped here. Its frequency differs significantly among islands in the region (χ(2) = 206.5, df = 3, P < 0.001). rs387907171 remains significantly, although weakly, associated with lighter hair pigmentation (F = 10.28, R(2) = 0.0125, P = 0.0014). This association increases when sex and age (F = 20.68, R(2) = 0.074, P < 7.92 × 10(-13) ) are included as covariates. The rs387907171 SNP exhibits strong allele frequency differences among islands in Northern Island Melanesia. Its absence from Bougainville, as well as the weak association with decreased hair color, indicates that additional alleles contribute to the blondism phenotype. Its geographic distribution suggests that a Lapita-mediated model for the dispersal of the derived allele at rs387907171 remains a viable evolutionary scenario. Am. J. Hum. Biol. 28:431-435, 2016. © 2015 Wiley Periodicals, Inc.


Pyrosequencing reveals bacterial diversity in Korean traditional wheat-based nuruk.
The emerging global importance of Korea's alcoholic beverages emphasizes the need for quality enhancement of nuruk, a traditional Korean cereal starter that is used extensively in traditional brewing. Apart from fungi and yeasts, bacteria known to be ubiquitously present are also a part of the nuruk ecosystem and are known to influence fermentation activity by influencing fermentation favorable factors. In the current study, bacterial diversity and temporal variations in the traditional wheat-based nuruk, fermented at two representative temperature conditions for 30 days, along with two commercial wheat-based nuruk samples for comparison analysis were evaluated using libraries of PCR amplicons and 454 pyrosequencing targeting of the hypervariable regions V1 to V3 of the 16S rRNA gene. A total of 90,836 16S reads were analyzed and assigned to a total of 314, 321, and 141 Operational Taxonomic Units (OTUs) for nuruk A, B, and C, respectively. Diversity parameters clearly indicated nuruk B to be more diverse in terms of bacterial composition than nuruk A. Taxonomic assignments indicated that nuruk A was dominated by phylum Cyanobacteria, whereas nuruk B was dominated by phylum Actinobacteria. For both nuruk A and B, members of the phylum Firmicutes mostly converged into the family Bacillaceae; these microorganisms might be present in negligible numbers at the beginning but became significant as the fermentation progressed. The commercial samples were predominated by phylum Firmicutes, which is composed of Lactobacillaceae and Leoconostocaceae. The findings of this study provide new insights into understanding the changes in bacterial community structure during traditional nuruk starter production.


iNOS expression requires NADPH oxidase-dependent redox signaling in microvascular endothelial cells.
Redox regulation of inducible nitric oxide synthase (iNOS) expression was investigated in lipopolysaccharide and interferon-gamma (LPS + IFNgamma)-stimulated microvascular endothelial cells from mouse skeletal muscle. Unstimulated endothelial cells produced reactive oxygen species (ROS) sensitive to inhibition of NADPH oxidase (apocynin and DPI), mitochondrial respiration (rotenone) and NOS (L-NAME). LPS + IFNgamma caused a marked increase in ROS production; this increase was abolished by inhibition of NADPH oxidase (apocynin, DPI and p47phox deficiency). LPS + IFNgamma induced substantial expression of iNOS protein. iNOS expression was prevented by the antioxidant ascorbate and by NADPH oxidase inhibition (apocynin, DPI and p47phox deficiency), but not by inhibition of mitochondrial respiration (rotenone) and xanthine oxidase (allopurinol). iNOS expression also was prevented by selective antagonists of ERK, JNK, Jak2, and NFkappaB activation. LPS + IFNgamma stimulated activation/phosphorylation of ERK, JNK, and Jak2 and activation/degradation of IkappaB, but only the activation of JNK and Jak2 was sensitive to ascorbate, apocynin and p47phox deficiency. Ascorbate, apocynin and p47phox deficiency also inhibited the LPS + IFNgamma-induced DNA binding activity of transcription factors IRF1 and AP1 but not NFkappaB. In conclusion, LPS + IFNgamma-induced NFkappaB activation is necessary for iNOS induction but is not dependent on ROS signaling. LPS + IFNgamma-stimulated NADPH oxidase activity produces ROS that activate the JNK-AP1 and Jak2-IRF1 signaling pathways required for iNOS induction. Since blocking either NFkappaB activation or NADPH oxidase activity is sufficient to prevent iNOS expression, they are separate targets for therapeutic interventions that aim to modulate iNOS expression in sepsis.


Epilepsy, language, and social skills.
Language and social skills are essential for intrapersonal and interpersonal functioning and quality of life. Since epilepsy impacts these important domains of individuals' functioning, understanding the psychosocial and biological factors involved in the relationship among epilepsy, language, and social skills has important theoretical and clinical implications. This review first describes the psychosocial and biological factors involved in the association between language and social behavior in children and in adults and their relevance for epilepsy. It reviews the findings of studies of social skills and the few studies conducted on the inter-relationship of language and social skills in pediatric and adult epilepsy. The paper concludes with suggested future research and clinical directions that will enhance early identification and treatment of epilepsy patients at risk for impaired language and social skills.


Muscle capillaries and retinopathy among Israeli diabetics. With special reference to measurement techniques, relationship to age and the pericyte.
Our investigation of the capillaries of 64 Israeli diabetics confirm the fact that retinopathy is consistently associated with thickening of the basal lamina of peripheral muscle capillaries but the converse is not so. The change in pericapillary structure may affect the capillary function. The primary cell involved, either causally or as a consequence of the lexion, is the pericyte.


The effect of experimental diabetes on the molecular characteristics of soluble rat-tail tendon collagen.
Acid soluble rat-tail tendon collagen was prepared from animals rendered diabetic by treatment with either streptozotocin or alloxan and from matched controls. In comparison to the normal, the diabetic collagens consistently demonstrated decreased solubility of reconstituted fibrils, marked increase in intrinsic viscosity and a decreased ratio of alpha to beta components. Electrophoresis in sodium dodecyl sulfate-polyacrylamide gels revealed a marked decrease in migration of alpha1, alpha2, and beta components from both types of diabetic collagen. These data indicate that diabetic collagens are larger than normal and are capable of higher degrees of polymerization due to increased intra- and inter-molecular interactions. These changes could explain, in part, the altered response of diabetic connective tissues to inflammation and trauma.


TLR7 Agonists Modulate the Activation of Human Conjunctival Epithelial Cells Induced by IL-1β via the ERK1/2 Signaling Pathway.
Conjunctival epithelia cells play an important role in the development of allergic reactions. TLR7 agonists have been shown in studies to increase the body's immunological tolerance by controlling the proportion of Th1/Th2 cells, although it is still unknown what impact this has on conjunctival epithelial cells. In this study, we examined the effect of TLR7 agonists on the inflammatory-activation of conjunctival epithelial cells induced by IL-1β. Quantitative PCR and ELISA analysis confirmed that TLR7 agonists could impair the proinflammatory cytokines released by the epithelia cells, whereas pro-inflammatory cytokines led to subsequent reactive oxygen species and neutrophil chemotaxis. Phosphorylation analysis and nucleocytoplasmic separation further confirmed that TLR7 agonists inhibit IL-1β-induced epithelia cells activation and ATP depletion via modulating the cytoplasmic residence of ERK1/2. Our finding indicated that TLR7 of conjunctival epithelia cells could be as a potent anti-inflammatory target for the ocular surface. And TLR7 agonists may become potential new drug for the treatment of allergic conjunctivitis.


Chromosome heteromorphisms: an impact on infertility.
Cytogenetic heteromorphisms are described as heritable variations at specific chromosomal regions without a proven impact on phenotype. We compared the presence of chromosome heteromorphisms in the karyotypes of two patient groups. The first group of patients consisted of 276 individuals of 138 infertile couples. The second group, consisted of 1,130 amniocentesis samples. This group was considered to be a sample of the fertile population, as the fetus being karyotyped is the result of a spontaneous pregnancy. Fetal karyotyping was made due to the standard indications for prenatal diagnosis, such as abnormal maternal serum screening results. Eighteen infertile patients (6.52%) and twenty fetuses (1.77%) were found to have chromosome heteromorphisms. The difference between the two groups was statistically significant (p < 0.0001). These results are consistent with other similar studies that suggest the yet undefined relationship between chromosome heteromorphisms and infertility.


Effect of a single 1200 Mg dose of Mucinex® on mucociliary and cough clearance during an acute respiratory tract infection.
Observational studies suggest that orally administered guaifenesin (GGE) may thin lower respiratory tract secretions but none have examined its effects on mucociliary and cough clearance (MCC/CC) during a respiratory tract infection (RTI). The current study was a randomized, parallel-group, double-blind, placebo-controlled study in non-smoking adults who suffered from an acute upper RTI. We assessed the effects of a single dose of Mucinex(®) 1200 mg (2 × 600 mg extended release tablets) (ER GGE) on 1) MCC/CC by assessing the rate of removal from the lung of inhaled radioactive tracer particles (Tc99m-sulfur colloid), 2) sputum dynamic rheology by stress/strain creep transformation over the linear part of the curve, 3) sessile drop interfacial tension by the deNouy ring technique, and 4) subjective symptom measures. MCC was measured during the morning (period 1) and compared to that in the afternoon 4 h later (period 2) immediately following either drug (n = 19) or placebo (n = 19). For both period 1 and 2 subjects performed 60 voluntary coughs from 60 to 90 min after inhalation of radio-labeled aerosol for a measure of CC. Sputum properties were measured from subjects who expectorated sputum during the cough period post treatment (n = 8-12 for each cohort). We found no effect of ER GGE on MCC or CC compared to placebo. MCC through 60 min for period 1 vs. 2 = 8.3 vs. 11.8% (placebo) and = 9.7 vs. 11.1% (drug) (NS) and CC for period 1 vs. 2 was 9.9 vs. 9.1% (placebo) and 10.8 vs. 5.6% (drug) (NS). There was no significant difference in sputum biophysical properties after administration of drug or placebo. There was no significant effect of a single dose of ER GGE on MCC/CC or on sputum biophysical properties compared to placebo in this population of adult patients with an acute RTI. ClinicalTrials.gov Identifier: NCT01114581.


Effects of varying degrees of doneness on the formation of heterocyclic aromatic amines in chicken and beef satay.
The study was carried out to determine the effect of cooking method on Heterocyclic Aromatic Amines (HAs) concentration in grilled chicken and beef (satay). Six common HAs were investigated: 2-amino-3-methylimidazo[4,5-f]quinolone (IQ), 2amino 3,4dimethylimidazo [4,5f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8 trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-3,7,8trimethylimidazo [4,5-f]quinoxaline (7,8-DiMeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Chicken and beef satay samples were grilled to medium and well done level of doneness. Charcoal grilled (treatment A), microwave pre-treatment prior to grilling (treatment B), and microwave-deep fried (treatment C) were applied to beef and chicken satay samples. The satay samples which were microwaved prior to grilling (B) showed significantly (p<0.05) lower HAs concentration as compared to those charcoal grilled (A). Both medium and well done cooked beef and chicken satay samples that were microwaved and deep fried (C) as an alternative method to grilling were proven to produce significantly lesser HAs as compared to charcoal-grilled (A) and microwaved prior to grilling (B).


Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection.
The double-stranded (ds) RNA-dependent protein kinase PKR is considered to play an important role in interferon's (IFN's) response to viral infection. Here, we demonstrate that mice lacking PKR are predisposed to lethal intranasal infection by the usually innocuous vesicular stomatitis virus, and also display increased susceptibility to influenza virus infection. Our data indicate that in normal cells, PKR primarily prevents virus replication by inhibiting the translation of viral mRNAs through phosphorylation of eIF2alpha, while concomitantly assisting in the production of autocrine IFN and the establishment of an antiviral state. These results show that PKR is an essential component of innate immunity that acts early in host defense prior to the onset of IFN counteraction and the acquired immune response.


A histochemical and immunohistological study of a testicular malignant teratoma containing embryonic and extraembryonic elements in various stages of development.
A testicular malignant teratoma containing embryoid bodies and other embryonic and extra-embryonic structures in various stages of development has been examined by several histochemical and immunohistological techniques to study the distribution of various substances in the teratomatous elements. The substances demonstrated included various types of mucins; argyrophil, argentaffin, Paneth cells and haemosiderin granules; alpha-fetoprotein, alpha-l-anti-trypsin, lysozyme, beta-HCG and CEA. The significance of the findings is discussed in relation to early embryonic development.


What sequence of pathogenetic events leads to acute ulcerative colitis?
The etiology of ulcerative colitis remains unresolved despite new immunologic, biochemical, and microbiologic observations made in this disease. A sequence of pathogenetic events has been adduced from abnormalities reported from human and experimental colitis with the express purpose of establishing priority of factors that may lead to an attack of acute ulcerative colitis. The presence of undefined bacterial metabolites in the colonic lumen causing specific breakdown of fatty acid oxidation in colonic epithelial cells is proposed to be the initiating event of the disease process that leads to an immune response and eicosanoid response perpetuating epithelial cell damage. The proposals embody the thesis that primary metabolic damage to colonocytes determines the clinical and pathologic manifestations of ulcerative colitis.


Tritiated thymidine experiments in the cat: a description of techniques and experiments to define the time-course of radioactive thymidine availability.
Tritiated thymidine [(3H]thymidine) autoradiographic techniques have been used to define birthdates for cells in a variety of animals. In an effort to include [3H]thymidine experiments in our ongoing studies of visual system development, we have used an intrauterine injection procedure that affords [3H]thymidine labeling of dividing nerve cells in the cat. This report contains a detailed description of the injection procedures used, as well as the results of experiments undertaken to define the period of time during which the exogenous [3H]thymidine introduced by such injections remains available for uptake.


Business law issues for assisted reproductive technology practices and practitioners: considerations for sales or mergers of fertility practices.
To succeed in the assisted reproductive technology industry, physician owners of fertility practices have to develop a wide array of business skills and expertise. In today's business world, a natural next step for many assisted reproductive practices is exploring potential mergers, sales, or acquisitions. This article will explore what factors physician owners of fertility practices should consider before pursuing a potential sale or merger; how to prepare for such a transaction; and what to expect once a transaction is underway.


SARS-CoV-2 Spike S1-specific IgG kinetic profiles following mRNA or vector-based vaccination in the general Dutch population show distinct kinetics.
mRNA- and vector-based vaccines are used at a large scale to prevent COVID-19. We compared Spike S1-specific (S1) IgG antibodies after vaccination with mRNA-based (Comirnaty, Spikevax) or vector-based (Janssen, Vaxzevria) vaccines, using samples from a Dutch nationwide cohort. In adults 18-64 years old (n = 2412), the median vaccination interval between the two doses was 77 days for Vaxzevria (interquartile range, IQR: 69-77), 35 days (28-35) for Comirnaty and 33 days (28-35) for Spikevax. mRNA vaccines induced faster inclines and higher S1 antibodies compared to vector-based vaccines. For all vaccines, one dose resulted in boosting of S1 antibodies in adults with a history of SARS-CoV-2 infection. For Comirnaty, two to four months following the second dose (n = 196), S1 antibodies in adults aged 18-64 years old (436 BAU/mL, IQR: 328-891) were less variable and median concentrations higher compared to those in persons ≥ 80 years old (366, 177-743), but differences were not statistically significant (p > 0.100). Nearly all participants seroconverted following COVID-19 vaccination, including the aging population. These data confirm results from controlled vaccine trials in a general population, including vulnerable groups.


The initiation, continuation, and termination of spontaneous episodes of circus movements in the pregnant myometrium of the rat.
The objectives of this study were to determine the mechanisms responsible for the initiation and the termination of episodes of circus movements and to describe the characteristics of these circuits in rat myometrium. By means of simultaneous recordings from 240 sites in Wistar rats at 17, 19, or 21 days' gestation, a spatial and temporal analysis was performed on the electrical activation from the beginning until the end of 22 episodes of circus movements. The initiation of reentry was caused by (1) transient unexcitable areas at the beginning of the burst or (2) lines of conduction blocks. Circus movements were terminated by (1) reversal of recruitment (decruitment) at the end of the burst, (2) occurrence of lines of conduction blocks, or (3) interruption of the circuit. On average circuits rotated for 6 revolutions during 2 seconds. In most cases circuits remained stable; sometimes circuits drifted along the tissue and occasionally multiple wavelets were seen instead of a single circuit. Spatial nonhomogeneities in conduction caused by transient unexcitable areas play a major role in both the initiation and the termination of episodes of circus movements in the pregnant rat myo-metrium. In addition, most circuits remained in a single location, although sometimes meandering or even fibrillatory activity was seen.


Part 6. Education for value-informed nursing practice.
With the ongoing transition to value-based health care, a strong command of foundational economic concepts, like cost and value, and the ability to thoughtfully engage in value-informed nursing practice have become essential for the future of the nursing profession. Earlier in this six-part series, we explained value-informed nursing practice, its historical, economic, and ethical foundation, its promise for an environmentally responsible, innovation-driven future health care, and why its adoption requires a reframing of some of the nursing's professional norms and behaviors. This paper concludes the series with one of the most important issues-education for value-informed nursing practice. We begin by setting forth our vision of how nursing students will learn and apply value informed nursing practice, consider challenges that nurse educators will face, and offer some suggestions for engraining value into the consciousness of the nursing profession.


Establishing the minimal clinically important difference for the PROMIS Physical domains in cervical deformity patients.
Patient Reported Outcome Measurement Information System (PROMIS) instruments have been shown to correlate with established patient outcome metrics. The aim of this retrospective study was to determine the MCID for the PROMIS physical domains of Physical Function (PF), Pain Intensity (PI), and Pain Interference (Int) in a population of surgical cervical deformity (CD) patients. Surgical CD patients ≥ 18 years old with baseline (BL) and 3-month (3 M) HRQL data were isolated. Changes in HRQLs: ΔBL-3M. An anchor-based methodology was used. The cohort was divided into four groups: 'worse' (ΔEQ5D ≤ -0.12), 'unchanged' (≥0.12, but < -0.12), 'slightly improve' (>0.12, but ≤ 0.24), and 'markedly improved' (>0.24) [0.24 is the MCID for EQ5D]. PROMIS-PF, PI and Int at 3M was compared between 'slightly improved' and 'unchanged'. ROC computed discrete MCID values using the change in PROMIS that yielded the smallest difference between sensitivity ('slightly improved') and specificity ('unchanged'). We repeated anchor-based methods for the Ames-ISSG classification of severe deformity. 140 patients were included. EQ5D groups: 9 patients 'worse', 53 'unchanged', 20 'slightly improved', and 57 'markedly improved'. Patients classified as 'unchanged' exhibited a PROMIS-PF improvement of 2.9 ± 17.0 and those 'slightly improved' had an average gain of 13.3 ± 17.8. ROC analysis for the PROMIS-PF demonstrated an MCID of +2.26, for PROMIS-PI of -5.5, and PROMIS-Int of -5.4. In the Ames-ISSG TS-CL severe CD modifier, ROC analysis found MCIDs of PROMIS physical domains: PF of +0.5, PI of -5.2, and Int of -5.4. MCID for PROMIS physical domains were established for a cervical deformity population. MCID in PROMIS Physical Function was significantly lower for patients with severe cervical deformity.


Ultrastructure of pacinian corpuscle primary afferent terminals in the cat spinal cord.
The glabrous skin of the hindlimb of the cat contains 3 types of low-threshold mechanoreceptors: Pacinian corpuscles (PC), and slowly and rapidly adapting receptors. In the present study, 12 primary afferent fibers transmitting impulses from PC were injected intra-axonally with horseradish peroxidase (HRP) in the spinal cord to examine the morphology of their terminals in the dorsal horn. At the light microscopic level, terminal arborizations were observed in laminae II-VI of the dorsal horn, extending up to 7 mm rostrocaudally in and near the seventh lumbar segment. Bouton-like swellings, predominantly (67%) of the en passant type, were distributed in two discrete clusters, one concentrated rostrally in Rexed's laminae III-IV, and the other concentrated caudally in lamina V. At the electron microscopic level, a combination of morphometric and serial reconstructive analyses with 3 fibers revealed the following. Boutons labelled with HRP invariably contained clear round vesicles, approximately 40 nm in diameter. Labelled bouton sections had longest dimensions of 1.84 +/- 0.63 micron. Their shapes varied from rounded to elongated forms with occasional scalloped appearances. A majority (73%) of the contacts associated with HRP-filled boutons were made with dendritic spines and shafts. Thick postsynaptic densities were usually associated with these synapses, although thinner densities were also observed. 24% of the contacts made by labelled boutons were synapse-like contacts with unlabelled vesicle-containing structures. The vesicles in the unlabelled structures were usually pleomorphic, but sometimes round. These contacts were identified as 'synapse-like' because labelling obscured possible landmarks necessary for definitive identification of synapses. However, in most of these contacts, there was an accumulation of vesicles near the cleft on the unlabelled side, suggesting that the labelled boutons were postsynaptic. Only 3% of the contacts made by labelled boutons were axosomatic. The lengths of contacts with dendritic spines (0.49 +/- 0.23 micron) or with dendrites proper (0.45 +/- 0.20 micron) were significantly longer than those with vesicle-containing unlabelled structures (0.31 +/- 0.18 micron). The portions of cross-sectional bouton contours devoted to synaptic or synapse-like contacts accounted for 9-13% of the perimeters. The larger the bouton, the longer the summed lengths of contacts. Serial reconstruction of selected labelled boutons revealed both simple and quite complex synaptic organizations, including glomeruli with labelled boutons as the central component.(ABSTRACT TRUNCATED AT 400 WORDS)


Decreasing ventilator-associated pneumonia in the intensive care unit: a sustainable comprehensive quality improvement program.
An intensive care unit implemented an oral care bundle to decrease ventilator-associated pneumonia (VAP). A retrospective analysis comparing like time periods revealed the VAP rate per 1,000 ventilator-days dropped significantly from 10.5 to 0 (P = .016). The oral care bundle remains in place as of end of May 2011 and has proven to be a sustainable method for VAP prevention.


Pharmacologic treatment for children and adolescents with anxiety disorders.
Pediatric anxiety disorders are common illnesses that, if left untreated, may induce academic, family, and interpersonal problems. Cognitive-behavioral techniques and other psychotherapeutic interventions may be adequate for the treatment of most anxiety disorders. For patients with severe symptoms or for whom psychotherapeutic approaches are not adequate, medications are indicated. Among the available medications, the SSRIs are currently the first choice; however, other medications, such as the benzodiazepines and the TCAs, may be used alone or sometimes in combination with the SSRIs. Caution with respect to medication interactions and side effects is indicated. In particular, long-term side effects in these medications have not been well studied.


Socioeconomic inequalities in health outcomes among Thai older population in the era of Universal Health Coverage: trends and decomposition analysis.
Thailand's Universal Health Coverage (UHC) has been achieved since 2002 when the entire population are covered by three main public health security schemes: (1) Civil Servant Medical Benefit Scheme (CSMBS); (2) Social Security Scheme (SSS); and (3) Universal Coverage Scheme (UCS). Citizens have access to healthcare services at all life stages and are protected from catastrophic expenditure and medical impoverishment. However, there are health inequalities in both health outcomes and access to healthcare among older Thais. This study aims to: (1) assess the degrees of socioeconomic inequalities in health outcomes among the older Thai population during the period of Thailand's UHC implementation (2003-2019), and (2) explain socioeconomic inequalities in health outcomes through decomposition of the contributions made by Thailand's UHC policy and other health determinants. Data sets come from a four-year series of the National Health and Welfare Survey (HWS) between 2003 and 2019. The health outcome of interest was obtained from the Thai EQ-5D index. The Erreygers' concentration index (CI) was used to calculate the socioeconomic inequality in health outcomes. Multivariate methods were employed to decompose inequalities. Findings indicated Thai older adults (aged 50 and older) are healthier during the UHC implementation. Better health outcomes remain concentrated among the wealthier groups (pro-rich inequality). However, the degree of socioeconomic inequalities in health outcomes significantly declined by almost a factor-of-three (from CI = 0.061 in 2003 to CI = 0.024 in 2019) after the roll-out of the UHC. Decomposed results reported that Thailand's UHC, urban residence, and household wealth were major contributors in explaining pro-rich inequalities in health outcomes among Thai older adults. Older persons in Thailand have better health while health inequalities between the rich and the poor have substantially decreased. However, there is inequalities in health outcomes within all three national health security schemes in Thailand. Minimizing differences between schemes continues to be a crucial cornerstone to tackling health inequalities among the older population. At the same time, making Thailand's UHC sustainable is necessary through preparing financial sustainability and developing health resources to better serve an ageing society.


Unraveling antibiotic resistance mechanisms in Mycobacterium abscessus: the potential role of efflux pumps.
Mycobacterium abscessus is an opportunistic respiratory pathogen in patients with underlying lung disease. It is infamously known for its low treatment success rates because of its resistance to multiple classes of antibiotics. Further insight into M. abscessus resistance mechanisms is needed to improve treatment options. In this in vitro study, the role of efflux pumps in reaction to antibiotic stress is explored, as well as the ability of the putative efflux inhibitors, thioridazine and verapamil, to potentiate the activity of guideline-recommended antibiotics. To evaluate the effects of antibiotic stress on mycobacterial efflux pumps, M. abscessus subspecies abscessus was exposed to amikacin, cefoxitin, clarithromycin, clofazimine, and tigecycline for 24 hours. Transcriptomic responses were measured by RNA sequencing to gain insight into upregulation of efflux pump encoding genes. Subsequently, in time-kill kinetics assays, the above-mentioned antibiotics were combined with thioridazine and verapamil to evaluate their potentiating capacity. All five antibiotics led to a fold change of ≥2 Log2 in expression of one or more genes encoding transporter systems. This effect was most pronounced for the ribosome-targeting antibiotics amikacin, clarithromycin, and tigecycline. Time-kill kinetics assays demonstrated synergy between amikacin, tigecycline, clofazimine, cefoxitin, and both thioridazine and verapamil. Antibiotic stressors induce expression of efflux pump encoding genes in M. abscessus, especially antibiotics that target the ribosome. Putative efflux inhibitors thioridazine and verapamil show synergy with various guideline-recommended antibiotics, making them interesting candidates for the improvement of M. abscessus treatment.


Neuronal transmission of hippocampal CA1 neurones is modulated by corticotropin-like intermediate lobe peptide [CLIP; ACTH(18-39)].
The study was conducted to test whether CLIP [ACTH(18-39)] influences the neuronal transmission and the induction of long-term potentiation (LTP) in the hippocampus. The population spike was recorded in the hippocampal CA1 region of freely moving rats before and after intracerebroventricular (ICV) administration of CLIP in comparison to ACTH and saline (controls). After infusion of CLIP, the population spike amplitude (PSA) rose to about 200% of baseline values. After reaching this level, it was impossible to induce a further increase of PSA by tetanization. However, if the stimulus intensity was reduced to a new baseline level, electrically induced LTP could be observed. There were no significant changes after infusion of ACTH. Our results indicate that the ICV administration of CLIP leads to an enhancement of excitability in the hippocampal CA1 region, which might be independent of LTP.


Human infections of fish-borne trematodes in Vietnam: prevalence and molecular specific identification at an endemic commune in Nam Dinh province.
The prevalence of fish-borne trematodes in humans and their molecular identification was investigated in the Rang Dong commune of Nam Dinh province, Vietnam, between January 2009 and December 2010. A total of 405 people in this commune were interviewed on the habit of eating raw fish and all of their stool samples were collected using the Kato-Katz technique for examination of the presence of fish-borne trematodes. The worms (and eggs) were first morphologically examined, counted, described and identified, then the representative isolates were subjected for molecular species confirmation. A total of 385 adult flukes collected from 10 patients were morphologically identified to species and defined as Clonorchis sinensis (14.58%) in Opisthorchiidae family, Haplorchis taichui (32.29%), Haplorchis pumilio (52.08%) and Centrocestus formosanus (1.04%) in Heterophyidae family. A high rate (77.8%) of the interviewees was found to have the habit of eating raw fish. This habit was attributed to the high infection rate of fish-borne trematode in humans (22.72%; OR=2.486). The infection rate of fish-borne trematodes in males was higher (29.3%) than that in females (16.0%) and increased by age, reaching the highest in the patients aged 40-59 years (28.2-28.7%). The infection intensity of fish-borne trematode was found light (336 EPG). Adult flukes were collected from a group of the patients with the highest intensity of infection and subjected to molecular and phylogenetic analysis using a portion (326 bp) of mitochondrial cox1. Phylogenetic tree inferred from cox1 sequences using sequence data for 34 isolates of opisthorchid, heterophyid, fasciolid, paragonimid, schistosomid trematodes and taeniid cestodes revealed that they are distinct groups. The newly collected with the known clonorchid and heterophyid isolates form the well defined taxonomic groups, respectively, confirming that C. sinensis and Haplorchis spp. (H. pumilio and H. taichui) were among the collected samples.


Efficacy of mexiletine in the medium-term treatment of ventricular arrhythmias. A randomized, double-blind, crossover trial against placebo in ambulatory patients.
A double-blind, crossover study was designed to compare the safety and efficacy of mexiletine with that of placebo in reducing premature ventricular complexes (PVC) in ambulatory patients and to find out the dose which gives a good therapeutic response with a minimal incidence of side-effects. Twenty-six patients, who had on average 427.9 PVCs/hour, were admitted to the study. The doses given were designed to reduce the frequency of PVCs by 50% or more from the baseline value. Two out of the twenty-six patients stopped treatment because of major side-effects. In the remaining twenty-four patients the 3 weeks of treatment with mexiletine significantly reduced the rate of PVCs by comparison with placebo (-63.8% versus +7.5%). In the nineteen responders (per cent reduction of PVCs over 50%) the dose of mexiletine was 600 mg daily (200 mg every 8 hours). In the non-responders plasma levels of mexiletine proved to be in the therapeutic range, not in any way different from responders. The most frequent side-effects were digestive difficulties (fifteen patients taking mexiletine and six taking placebo). These results show that mexiletine is an effective anti-arrhythmic drug in the management of ventricular arrhythmias occurring in ambulatory patients. In the majority of patients mexiletine was found to be effective even at the lowest dose studied of 600 mg/day.


Lithium-induced Nephrotoxicity: A Case Report of Renal Cystic Disease Presenting as a Mass Lesion.
Lithium is an effective therapeutic agent used in the management of bipolar disorder. However, lithium is also associated with several side effects, including renal toxicity. We present a case of a symptomatic cystic mass lesion in the kidney of a patient who had a history of lithium therapy for the management of bipolar disorder.


Toxic shock syndrome due to group A beta-hemolytic streptococcus presenting with purpura fulminans and limb ischemia in a pediatric patient treated with early microsurgical arteriolysis.
We describe a 2.5 year-old child with toxic shock syndrome due to group A beta-hemolytic streptococcus (GABHS) who presented with purpura fulminans and limb ischemia treated with early microsurgical arteriolysis. The clinical picture of toxic shock syndrome (TSS) presenting with purpura fulminans and limb ischemia is an exceptionally uncommon finding in sepsis due to GABHS. This is the first case of purpura fulminans caused by GABHS reported in Europe and the third one described in the literature (Dhodapkar et al., 2000[1]; Renaud et a., 2011[2]).


Biofilm formation by selected microbial strains isolated from wastewater and their consortia: mercury resistance and removal potential.
Wastewater often contains an increased amount of mercury and, at the same time, resistant microorganisms. During wastewater treatment, a biofilm of indigenous microorganisms is often unavoidable. Therefore, the objective of this research is to isolate and identify microorganisms from wastewater and investigate their ability to form biofilms for possible application in mercury removal processes. The resistance of planktonic cells and their biofilms to the effects of mercury was investigated using Minimum Biofilm Eradication Concentration-High Throughput Plates. The formation of biofilms and the degree of resistance to mercury were confirmed in polystyrene microtiter plates with 96 wells. Biofilm on AMB Media carriers (Assisting Moving Bad Media) was quantified using the Bradford protein assay. The removal of mercury ions by biofilms formed on AMB Media carriers of selected isolates and their consortia was determined by a removal test in Erlenmeyer flasks simulating MBBR. All isolates in planktonic form showed some degree of resistance to mercury. The most resistant microorganisms (Enterobacter cloacae, Klebsiella oxytoca, Serratia odorifera, and Saccharomyces cerevisiae) were tested for their ability to form biofilms in the presence and absence of mercury, both in polystyrene plates and on ABM carriers. The results showed that among planktonic forms, K. oxytoca was the most resistant. A biofilm of the same microorganisms was more than 10-fold resistant. Most consortia biofilms had MBEC values > 100,000 μg/mL. Among individual biofilms, E. cloacae showed the highest mercury removal efficiency (97.81% for 10 days). Biofilm consortia composed of three species showed the best ability to remove mercury (96.64%-99.03% for 10 days). This study points to the importance of consortia of different types of wastewater microorganisms in the form of biofilms and suggests that they can be used to remove mercury in wastewater treatment bioreactors.


Time Course Change in Muscle Swelling: High-Intensity vs. Blood Flow Restriction Exercise.
This study determined the time course for changes in muscle swelling and plasma volume following high (HI) and low-intensity resistance exercise with blood-flow restriction (LI-BFR). Ten male participants (22.1±3.0 yrs) completed three experimental conditions: high-intensity exercise (HI - 80% of 1RM), low-intensity exercise with BFR (LI-BFR -20% of 1RM, and 160 mmHg of BFR), and control (CON - no exercise or BFR). Muscle cross-sectional area (mCSA), muscle thickness, thigh circumference, and percentage change in plasma volume (PV%∆) were measured. mCSA was significantly greater than rest values at 15 min post-exercise (p<0.01) for HI and LI-BFR, and at 75 min post-exercise (p<0.01) for HI. Muscle thickness was significantly greater than rest immediately post-exercise (p<0.01) and 30 min post-exercise (p<0.01) for HI and LI-BFR, and at 60 min post-exercise for HI (p=0.01). Muscle thickness was greater for BFR immediately post-exercise compared to HI (p=0.01) post-exercise. Thigh circumference was significantly greater from rest at 15 min post-exercise (p=0.01) and at 75 min post-exercise for both LI-BFR (p=0.03) and HI (p<0.01). PV%∆ significantly decreased from rest immediately post-exercise for both HI (p<0.01) and LI-BFR (p<0.01). In conclusion, BFR exercise induces changes in muscle swelling and plasma volume similar to those observed at high-intensities.


Identification and comparison of rehabilitation goals after multiple injuries: an ICF analysis of the patients', physiotherapists' and other allied professionals' reported goals.
To explore and compare severely injured patients' rehabilitation goals with respect to their functioning and the reported goals of rehabilitation professionals. A prospective cohort study, including longitudinal data on patients' functioning and cross-sectional data from the patients' and professionals' goal descriptions. Sixty-six patients (53 men, 13 women, mean age 35 (standard deviation 13.8) years) with multiple injuries with a New Injury Severity Score >15 and 76 physiotherapists and other municipal rehabilitation professionals/services. Patient questionnaire and interview were applied after return home and a further questionnaire one year post-injury. Short-Form Health Survey was used for self-assessed health. A questionnaire was applied to the professionals. Rehabilitation goals were reported by patients and professionals. International Classification of Functioning, Disability and Health coding of the goals was performed. Short-Form Health Survey scores were below those of the general population. The patients' goals concerned body functions/structures (8.6%), activities (16.2%) and participation (31.7%). The professionals, mainly physiotherapists, reported few participation goals (10.7%). Agreement between the patients' and professionals' goals were poor, with kappa scores < or =0.20 for musculoskeletal functions/structures, self-care, mobility, interpersonal interactions/relationships, work and recreation/leisure. A statisticaly significant difference between patients' and professionals' goals was demonstrated for musculoskeletal functions/structures (p<0.001), interpersonal interactions/relationships (p=0.002), work (p=0.001) and recreation/leisure (p=0.002). The patients mainly reported activity and participation goals. There was poor agreement between patients and professionals for body functions and participation goals.


Mutational analysis of HIV-2 Vpx shows that proline residue 109 in the poly-proline motif regulates degradation of SAMHD1.
In this study, we performed a mutational analysis to determine whether the mechanism by which HIV-2 Vpx confers the capacity for infectivity and viral replication in macrophages is solely dependent on its ability to degrade the host antiviral factor SAMHD1. Contrary to expectations, we demonstrated that P(109) in the C-terminal poly-proline motif of HIV-2 Vpx has two unique roles: to facilitate the specific degradation of SAMHD1 in macrophages, and to facilitate multimerization of Vpx, therefore preventing SAMHD1 degradation in the presence of high levels of Vpx.


A relapse prevention group for patients with bipolar and substance use disorders.
Although bipolar disorder is the Axis I disorder associated with the highest risk of having a coexisting substance use disorder, no specific treatment approaches for this dually diagnosed patient population have thus far been developed. This paper describes a 20-session relapse prevention group therapy that the authors have developed for the treatment of patients with coexisting bipolar disorder and substance use disorder. The treatment uses an integrated approach by discussing topics that are relevant to both disorders and by highlighting common aspects of recovery from and relapse to each disorder.


Motorcycle exhaust particles induce IL-8 production through NF-kappaB activation in human airway epithelial cells.
Motorcycle exhaust particles (MEP) are among the major air pollutants, especially in urban area of Taiwan. In our previous study, data showed that MEP induce proinflammatory and proallergic response profiles in BALB/c mice. Effects of MEP on interleukin (IL)-8 production in A549 human airway epithelial cells were further investigated in this study. It was found that MEP enhanced IL-8 protein and mRNA expression in human epithelial cells. Pretreatment with an NF-kappaB inhibitor (1 mM PDTC), extracellular signal-regulated kinase (ERK) inhibitor (50 microM PD98059), JNK inhibitor (25 microM SP600125), p38 inhibitor (2 microM SB203580), and three antioxidants (500 U/ml superoxide dismutase [SOD], 50 microM vitamin E, 10 mMN-acetylcysteine [NAC]) attenuated the MEP-induced increase in IL-8 production. Through further, direct detection of nuclear factor (NF)-kappaB activation in epithelial cells using immunoblotting of nuclear p65 and NF-kappaB reporter assay, data showed that MEP induced nuclear translocation of p65 and enhancement of NF-kappaB luciferase gene expression. MEP also induced activation of ERK, JNK, and p38 signaling pathways and produced an increase of oxidative stress in A549 cells. By using mitogen-activated protein kinase (MAPK) inhibitors and antioxidant, it was demonstrated that ERK inhibitor, JNK inhibitor, and antioxidants but not p38 inhibitor attenuated the MEP-induced increase in NF-kappaB reporter activity. In conclusion, evidence shows that filter-trapped particles emitted from unleaded gasoline-fueled, two-stroke motorcycle engines induce an increase in IL-8 production by activation of NF-kappaB in human airway epithelial cells.


Biodegradability assessment of food additives using OECD 301F respirometric test.
The ready biodegradability of twenty food additives, belonging to the classes of artificial sweeteners, natural sweeteners, preservatives and colorings, was investigated using activated sludge as inoculum and OECD 301F respirometric test. According to the results, saccharin, aspartame, sodium cyclamate, xylitol, erythritol, maltitol, potassium sorbate, benzoic acid and sodium ascorbate are characterized as readily biodegradable compounds, partial biodegradation (<60% during the test) was noticed for steviol, inulin, alitame, curcumin, ponceau 4R and tartrazine, while no biodegradation was observed for the other five compounds. The duration of lag phase before the start of biodegradation varied between the target compounds, while their ultimate biodegradation half-life values ranged between 0.7 ± 0.1 days (benzoic acid) and 24.6 ± 1.0 days (curcumin). The expected removal of target compounds due to ultimate biodegradation mechanism was estimated for a biological wastewater treatment system operated at a retention time of one day and percentages higher than 40% were calculated for sodium cyclamate, potassium sorbate and benzoic acid. Higher removal percentages are expected in full-scale Sewage Treatment Plants (STPs) due to the contribution of other mechanisms such as sorption to suspended solids, (bio)transformation and co-metabolic phenomena. Further biodegradation experiments should be conducted under different experimental conditions for the food additives that did not fulfill the requirements of the applied protocol. Future studies should also focus on the occurrence and fate of food colorants and natural sweeteners in full-scale STPs.


Control of Crystallinity of Vinylene-Linked Two-Dimensional Conjugated Polymers by Rational Monomer Design.
The interest in two-dimensional conjugated polymers (2D CPs) has increased significantly in recent years. In particular, vinylene-linked 2D CPs with fully in-plane sp2 -carbon-conjugated structures, high thermal and chemical stability, have become the focus of attention. Although the Horner-Wadsworth-Emmons (HWE) reaction has been recently demonstrated in synthesizing vinylene-linked 2D CPs, it remains largely unexplored due to the challenge in synthesis. In this work, we reveal the control of crystallinity of 2D CPs during the solvothermal synthesis of 2D-poly(phenylene-quinoxaline-vinylene)s (2D-PPQVs) and 2D-poly(phenylene-vinylene)s through the HWE polycondensation. The employment of fluorinated phosphonates and rigid aldehyde building blocks is demonstrated as crucial factors in enhancing the crystallinity of the obtained 2D CPs. Density functional theory (DFT) calculations reveal the critical role of the fluorinated phosphonate in enhancing the reversibility of the (semi)reversible C-C single bond formation.


The development and evaluation of a clinical test of surgical resident proficiency.
The two purposes of this study were to develop a clinical test of surgical resident proficiency and to compare this clinical test with currently applied methods of resident evaluation. Appendicitis is a common surgical disease, and its accurate diagnosis depends largely on clinical acumen. Ten third-year surgical residents prospectively evaluated 107 patients admitted because of suspected appendicitis. After taking a history, performing a physical examination, and reviewing laboratory data, these residents were asked to state, as a percentage, the likelihood that each patient had appendicitis. Sixty-three patients had appendicitis documented by pathologic inspection after appendectomy. Forty-four patients did not have appendicitis, as was determined by operation (17) or by in-house observation and resolution of abdominal pain (27). These outcomes were used to calculate a diagnostic ability score (DAS) for each resident. Residents were evaluated by standard methods including in-service examinations and monthly evaluations by the attending staff. Residents were also evaluated by nonstandard, but potentially useful, neuropsychologic and psychologic tests, including the trail making test, the Ravens progressive matrices test, the paced auditory serial addition test (PASAT), the grooved pegboard test of manual dexterity, and the profile of mood states (POMS) psychologic questionnaire. Cumulative scores were calculated and compared by multiple regression with coefficient variance analysis. The correlation (R2) of DAS with standard evaluation techniques was as follows: In-service (0.055), faculty (0.508), trails (-0.293), Ravens (0.028), PASAT (0.251), dexterity (0.432), POMS (0.381). We found that (1) the DAS is a discriminating clinical test; (2) the DAS correlates with subjective faculty evaluation; and (3) the DAS does not correlate with in-service examination scores. We conclude that faculty evaluation remains the best currently applied test of surgical resident clinical proficiency as measured by the DAS.


Emissions of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs) in Iran.
The aim of this study was estimation of PCDD/PCDFs emissions from various sources in Iran. The results indicated total PCDD/PCDFs emissions in Iran in 2010, was 1,957 g TEQ. Of this amount, about 705.8, 0.5, 463.5, 144.1 and 643.2 g TEQ/year was released to air, water, land, products, and in residues, respectively. Open burning processes and metal production are the major contributors to be known environmental sources of PCDD/PCDFs that contribute to about 70% of total PCDD/PCDFs emissions in Iran. The results showed that total PCDD/PCDFs emissions in Iran per inhabitant were about 26.5 g TEQ/million that is high relatively.


A multi-stimuli-responsive nanochannel inspired by biological disulfide bond.
Disulfide bonds exist widely in channel protein and play an essential role in matter exchange and signal transduction (e.g., rhodopsin, canonical transient receptor potential 5 (TRPC5)). The research on disulfide bond in nanochannel is significant for the cognition of their biological functions. However, the fragility of biological channel limits the in-situ study and practical application. Herein, an innovative biologically-inspired artificial nanochannel based on disulfide bond (NCDS) with excellent durability, adjustable surface property is proposed. The constructed NCDS has a multi-response to UV-light, thiol (e.g., cysteine (Cys)) or pH stimulation, and can obtain reversibility after regulation by hydrogen peroxide (H2O2) or H+. The biomimetic NCDS shows great potential in biosensor and intelligent response design. This study also shines new light to channel protein based on disulfide bond that despite the nanochannel has specificity, it will be modulated by the change of nature environment, such as UV-light and chemical microenvironment (e.g., redox state and pH), which might be the reason of some disease.


Effect of age on the role of Rho-kinase in short-term partial bladder outlet obstruction.
We examined the expression of Rho-kinase (ROK) isoforms in young and old rabbits' detrusor smooth muscles (SM) during the progression of short-term partial bladder outlet obstruction and correlated them with the time course of obstruction. We obtained detrusor samples from bladders after 1, 3, 7, and 14 days of obstruction and also sham-operated control rabbits. We used reverse transcriptase-polymerase chain reaction, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and Western blotting to determine the relative levels of ROK isoform expression at the mRNA and protein levels. Bladder weight for young rabbits increased between 1 and 7 days' obstruction and came back toward control levels at 14 days' obstruction. In old rabbits, bladder weight increased after obstruction, reaching a maximum at 3 days and remaining at this level throughout the 14 days. In young rabbits, the expression of ROKalpha increased in 1- to 7-day obstructed groups and decreased in the 14-day group, whereas it increased progressively in the old rabbits at both the mRNA and protein levels. There was a significant decrease in the expression of ROKbeta in young obstructed rabbits, which gradually decreased during the course of 1- to 7-day obstruction period and increased after 14 days of obstruction. In old groups, there was a decrease in expression after 1 day of obstruction and values remained at a decreased level throughout the course of the study. Young rabbit bladders are better able to adapt to bladder outlet obstruction and ROK isoforms respond in a similar way.


Breath ammonia testing for diagnosis of hepatic encephalopathy.
Measurement of arterial ammonia has been used as a diagnostic test for hepatic encephalopathy, but obtaining an arterial specimen is an invasive procedure. The aim of this study was to evaluate the ability of a minimally invasive, highly sensitive optical sensing device to detect ammonia in the breath of patients with end-stage liver disease and to evaluate the correlation of breath ammonia levels, arterial ammonia levels, and psychometric testing. Fifteen subjects with liver cirrhosis and clinical evidence of hepatic encephalopathy underwent mini-mental status examination, number connection test, focused neurological examination, and arterial ammonia testing. On the same day, breath ammonia testing was performed using an apparatus that consists of a sensor (a thin membrane embedded with a pH-sensitive dye) attached to a fiberoptic apparatus that detects optical absorption. Helicobacter pylori testing was performed using the 14C urea breath test. A positive correlation was found between arterial ammonia level and time to complete the number connection test (r = 0.31, P = 0.03). However, a negative correlation was found between breath ammonia level and number connection testing (r = -0.55, P = 0.03). Furthermore, no correlation was found between breath and arterial ammonia levels (r = -0.005, P = 0.98). There is a significant correlation between the trailmaking test and arterial ammonia levels in patients with cirrhosis. However, no correlation was found between breath and arterial ammonia levels using the fiberoptic ammonia sensor apparatus in this small study.


Characterisation and translation studies of messenger RNA from the human malaria parasite Plasmodium falciparum and construction of a cDNA library.
RNA was isolated from trophozoites, schizonts and mixed populations of Plasmodium falciparum. 5% of the total was poly(A+) message, of average length 1.2 kb (10-12 kb maximum) and a poly(A) content of 10%. The mRNA fractions could be translated in vitro by reticulocyte lysates supplemented either with exogenous or P. falciparum tRNA. The patterns from two independent isolates, one cloned (T9-94) and one uncloned (K1) were virtually identical. Major translation products from 16-230 kDa have been measured. The most abundant is lactate dehydrogenase (34.8 kDa). Trophozoite mRNA codes principally for proteins of less than or equal to 93 kDa, while schizont mRNA codes for additional proteins of higher molecular mass. There are marked similarities between the in vitro translation products and proteins synthesised in vivo in synchronous cultures. A number of schizont mRNA translation products (principally those of 230, 203, 185, 170, 115, 101 and 71 kDa) are specifically precipitated without post-translational modification by sera from humans exposed to malaria. A cDNA library has been constructed in phage lambda from total poly(A+) RNA and partially characterised. About 10% of the clones derive from abundant mRNA sequences. Putative actin clones have been isolated from this library and the parasite actin mRNA sized at approx. 2.8 kb.


Real-time imaging of nitric oxide production in living cells with 1,3,5,7-tetramethyl-2,6-dicarbethoxy-8-(3',4'-diaminophenyl)-difluoroboradiaza-s-indacence by invert fluorescence microscope.
Although the importance of nitric oxide (NO) as a signalling molecule in many biological processes is becoming increasingly evident, many proposed and potential biological functions of NO still remain unclear. Bioimaging is a good technique to visualize observation of nitric oxide in biological samples. In this report, a fluorescent probe, 1,3,5,7-tetramethyl-2,6-dicarbethoxy-8-(3',4'-diaminophenyl)-difluoroboradiaza-s-indacence (TMDCDABODIPY), has been first applied to real-time image NO produced in PC12 cells, Sf9 cells and human vascular endothelial cells at the presence of l-arginine with inverted fluorescence microscope. NO production in the cells is successfully captured and imaged with fine temporal and spatial resolution. The results prove that the probe combined with inverted fluorescence microscope can be developed into a sensitive and selective method for further study of NO release from cells.


Shortened leukocyte telomere length in type 2 diabetes mellitus: genetic polymorphisms in mitochondrial uncoupling proteins and telomeric pathways.
Current debate in type 2 diabetes (T2DM) has focused on shortened leukocyte telomere length (LTL) as the result of a number of possible causes, including polymorphisms in mitochondrial uncoupling proteins (UCPs) leading to oxidative stress, telomere regulatory pathway gene polymorphisms, or as a direct result of associated cardiovascular complications inducing tissue organ inflammation and oxidative stress. There is evidence that a heritable shorter telomere trait is a risk factor for development of T2DM. This review discusses the contribution and balance of genetic regulation of UCPs and telomere pathways in the context of T2DM. We discuss genotypes that are well known to influence the shortening of LTL, in particular OBFC1 and telomerase genotypes such as TERC. Interestingly, the interaction between short telomeres and T2DM risk appears to involve mitochondrial dysfunction as an intermediate process. A hypothesis is presented that genetic heterogeneity within UCPs may directly affect oxidative stress that feeds back to influence the fine balance of telomere regulation, cell cycle regulation and diabetes risk and/or metabolic disease progression.


Reproducibility of blood oxygen level-dependent signal changes with end-tidal carbon dioxide alterations.
Hypercapnia has been utilized as a stimulus to elicit changes in cerebral blood flow (CBF). However, in many instances it has been delivered in a non-controlled method that is often difficult to reproduce. The purpose of this study was to examine the within- and between-visit reproducibility of blood oxygen level-dependent (BOLD) signal changes to an iso-oxic square wave alteration in end-tidal carbon dioxide partial pressure (Pet CO2 ). Two 3-Tesla (3T) MRI scans were performed on the same visit, with two square wave alterations administered per scan. The protocol was repeated on a separate visit with minimum of 3 days between scanning sessions. Pet CO2 was altered to stimulate changes in cerebral vascular reactivity (CVR), while Pet O2 was held constant. Eleven subjects (six females; mean age 26·5 ± 5·7 years) completed the full testing protocol. Excellent within-visit square wave reproducibility (ICC > 0·75) was observed. Similarly, square waves were reproducible between scanning sessions (ICC > 0·7). This study demonstrates BOLD signal changes in response to alterations in Pet CO2 are reproducible both within- and between-visit MRI scans.


Feedback of personal retinal images appears to have a motivational impact in people with non-proliferative diabetic retinopathy and suboptimal HbA1c: findings of a pilot study.
To conduct a pilot study to explore the potential impact of visual feedback of personal retinal images on diabetes outcomes. Twenty-five participants with non-proliferative diabetic retinopathy and suboptimal HbA(1c) (> 53 mmol/mol; > 7%) were randomized to receive visual feedback of their own retinal images or to a control group. At baseline and 3-month follow-up, HbA(1c), standard measures of beliefs, diabetes-related distress and self-care activities were assessed. In unadjusted models, relative to controls, the intervention group showed significantly greater improvement in HbA(1c) at 3-month follow-up (-0.6% vs. +0.3%, P < 0.01), as well as enhanced motivation to improve blood glucose management (P < 0.05). This small pilot study provides preliminary evidence that visual feedback of personal retinal images may offer a practical educational strategy for clinicians in eye care services to improve diabetes outcomes in non-target compliant patients. A fully powered randomized controlled trial is required to confirm these findings and determine the optimal use of feedback to produce sustained effects.


Proteoglycan alterations following immobilization and remobilization in the articular cartilage of young canine knee (stifle) joint.
The distribution of proteoglycans (PGs) at 11 sites on the knee (stifle joint) cartilage of young female beagle dogs was studied following cast immobilization for 11 weeks in 90 degrees flexion and after a subsequent remobilization for 15 weeks. Immobilization induced a reduction in PG uronic acid at all sites (mean of -38%), but the greatest depletion (-64%) occurred at the anterior and posterior extremes of the femoral condyles, i.e., at locations where the immobilized cartilage lost contact to the opposing cartilage. Following remobilization, the content of uronic acid remained lower than in the age-matched controls (-18% on average), particularly at the minimum contact sites most affected by immobilization (-33%). The chondroitin-6-sulfate to chondroitin-4-sulfate ratio was reduced by immobilization in most locations (average of -14%) and returned to control values after remobilization. There was no consistent change in the percentage of aggregating PGs observed in Sephacryl S-1000 gel filtration after immobilization or remobilization. However, following remobilization, the aggregating PGs showed an enhanced proportion of the slower mobility band in agarose gel electrophoresis, indicative of a larger monomer size. In the contralateral, load-bearing knee joint, both the uronic acid content and PG monomer type distribution were identical to those observed in the experimental joint, suggesting that the state reached after the remobilization period was due to factor(s) influencing both sides. The results suggest that contact forces between articulating surfaces are required to maintain normal PG content and that the control mechanism works locally at each cartilage site. Restriction of joint mobility and loading in young animals is concluded to cause persistent changes in cartilage matrix. Furthermore, the use of the contralateral joint as the sole control in this kind of studies, although experimentally convenient, seems not to be appropriate.


Cascade signal amplification sensing strategy for highly specific and sensitive detection of homologous microRNAs in different molecular subtypes of breast cancer.
Discriminative identification of homologous miRNAs in miRNA family with high specificity and sensitivity is crucial for accurate classification, diagnosis and prognosis of breast cancer. Herein, we report a reliable, sensitive, and selective assay by coupling fluorescence resonance energy transfer (FRET) with cascade signal amplification. The strategy is developed by designing two programmable DNA probes that can be triggered to shift from "off" to "on" state in a cascade hybridization reaction in the presence of target miRNA let-7a, leading to the generation of an amplified signal. The assay can detect concentrations as low as ∼3.0 pM let-7a and discriminate let-7a from other highly homologous members in the let-7 miRNA family. Moreover, it can also be used to determine let-7a levels at single-cell resolution and evaluate the drug efficacy of let-7a expression among various molecular types of breast cancer cell lines. The advantage of this assay is a combined result of signal generation and amplification triggered by target miRNA, which can satisfy an assay of analogous miRNA in a downregulated manner with high specificity. It has promising potential as a selective assay for homologous miRNAs in precision medicine.


Congenital diaphragmatic hernia: associated malformations--cystic adenomatoid malformation, extralobular sequestration, and laryngotracheoesophageal cleft: two case reports.
Two infants with unusual bronchopulmonary malformations associated with congenital diaphragmatic hernia (CDH) are presented. One infant had extralobular sequestration and cystic adenomatoid malformation of the lower lobe, in addition to a left-sided CDH. The second infant had a laryngotracheoesophageal cleft extending to the carina (type III) in addition to a left-sided CDH. These associated malformations can have major implications in terms of diagnosis, resuscitation, and surgical management of infants with CDH.


Enhancing Sulfur Redox Conversion of Active Iron Sites by Modulation of Electronic Density for Advanced Lithium-Sulfur Battery.
Despite lithium-sulfur (Li-S) batteries possessing ultrahigh energy density as great promising energy storage devices, the suppressing shuttle effect and improving sulfur redox reaction (SROR) are vital for their practical application. Developing high-activity electrocatalysts for enhancing the SROR kinetics is a major challenge for the application of Li-S batteries. Herein, single-molecule iron phthalocyanine species are anchored on the N and P dual-doped porous carbon nanosheets (Fe-NPPC) via axial Fe-N coordination to optimize the electronic structure of active centers. The Fe-NPPC can promote the catalytic conversion of polysulfides by modulation of the electronic density in active moieties, endowing the Li-S battery with a high reversible capacity of 1023 mAh g-1 at 1 C as well as an ultralow capacity decay of 0.035% per cycle over 1500 cycles. Even with a high sulfur loading of 7.1 mg cm-2 , the Li-S battery delivers a high areal capacity of 4.8 mAh cm-2 after 150 cycles at 0.2 C. With further increasing the sulfur loading to 9.2 mg cm-2 , an excellent areal capacity of up to 9.3 mAh cm-2 is obtained at 0.1 C.


Office- and Bedside-based Screening for Cognitive Impairment and the Dementias: Which Tools to Use, Interpreting the Results, and What Are the Next Steps?
Elderly patients and their families are concerned about the patients' cognitive abilities, and cognitive screening is an efficient diagnostic tool, as long as clinicians administer the screens in a standardized manner and interpret the screen results accurately. The following brief summary reviews commonly used screening instruments and provides information about how to interpret screening test results. It concludes by showing how cognitive screening fits into a four-step process (Education, Screening, Follow-up, and Referral) of how to respond to patients with cognitive concerns.


[Aspergillus in airway material : Ignore or treat?]
Fungi of the genus Aspergillus are ubiquitously present. Even though humans inhale Aspergillus spores daily under natural conditions, Aspergillus-associated pulmonary diseases only occur under special circumstances. Whether an Aspergillus-associated disease develops and which type of Aspergillus-associated disease develops depends on the constitution of the host. The spectrum of Aspergillus-associated pulmonary diseases ranges from allergic diseases, such as hypersensitivity pneumonitis to allergic infectious diseases, such as allergic bronchopulmonary aspergillosis (ABPA) and bronchocentric granulomatosis (BG) to infectious diseases, such as invasive (IA) or semi-invasive aspergillosis (SIA) and chronic pulmonary aspergillosis (CPA). Identification of Aspergillus spp. from sputum or bronchopulmonary secretions is not sufficient for a definitive diagnosis of Aspergillus-associated infections. The gold standard is the identification of Aspergillus spp. from lung tissue by culture or by histopathological methods; however, in clinical practice the decision to initiate antifungal therapy is more often based on immunological methods, such as the detection of Aspergillus-specific IgG antibodies from peripheral blood or galactomannan antigens from bronchoalveolar lavages. Acute IA or SIA infections have a high mortality and require immediate antifungal therapy. With rare exceptions CPA cannot be cured by medicinal therapy alone; however, active CPA can be brought into remission with antifungal therapy. Eradication of Aspergillus in CPA can as a rule only be successful using a combined antimycotic and surgical intervention.


Ultrastructural analysis of prefrontal cortical inputs to the rat amygdala: spatial relationships to presumed dopamine axons and D1 and D2 receptors.
Projections from the prefrontal cortex (PFC) to the amygdala (AMG) regulate affective behaviors in a manner that is modulated by dopamine (DA). Although PFC and DA inputs overlap within the basolateral nucleus (BLA) and intercalated cell masses (ICMs), the spatial relationship between these afferents has not been investigated, nor is it known how DA D1 (D1R) and D2 (D2R) receptors are localized in relationship to PFC terminals. We therefore combined tract-tracing from the rat PFC to the AMG with immunocytochemical labeling of tyrosine hydroxylase (TH) to identify presumed DA axons or D1R and D2R. In both the ICMs and BLA, PFC terminals formed asymmetric synapses onto spines that typically did not receive secondary synaptic inputs. TH-immunoreactive (-ir) fibers in the adjacent neuropil typically contacted different structures. Although PFC and TH-ir axons were sometimes apposed to the same dendrites or to each other, PFC terminals only rarely synapsed onto dendrites that also received synapses from TH-ir axons. D1R-ir spines and dendrites were observed commonly within the ICMs but less frequently within the BLA, and PFC axons in the ICMs occasionally synapsed onto D1R-ir spines. Within both regions, D2R-ir spines, dendrites, and axons were observed. PFC terminals occasionally contained presynaptic labeling for D2R but were not observed to synapse onto D2R-ir targets. The infrequent observation of synaptic convergence between PFC and presumed DA terminals within the AMG suggests that DA modulates PFC inputs primarily via extrasynaptic mechanisms, a conclusion supported by the localization of D2R within and D1R postsynaptic to PFC terminals.


Sexual dimorphism in the vasopressin system: lack of an altered behavioral phenotype in female V1a receptor knockout mice.
Previous findings with an AVP V1a receptor knockout mouse (V1aRKO) demonstrate a significant role for this receptor in anxiety-like behavior in males. Here we report the lack of anxiety-like effects of the null mutation in female mice. V1aRKO females performed normally on all tests for anxiety-like behavior. This sex difference may be due to the sexual dimorphism in the extra-hypothalamic vasopressin system, with males having significantly more vasopressin fibers in this system.


Stimulation of Toll-Like Receptors profoundly influences the titer of polyreactive antibodies in the circulation.
Polyreactive antibodies are a major component of the natural antibody repertoire and bind to a variety of structurally unrelated molecules. These antibodies are thought to provide a first line of defense against bacterial infections and play a major role in the clearance of apoptotic cells. What triggers the secretion of these antibodies has remained an enigma. Using a surrogate assay for measuring polyreactive antibodies, we found that about 50% of serum IgM is polyreactive and that stimulation of TLR4(+/+), but not TLR4(-/-), mice resulted in a 40 fold increase in polyreactive antibodies. Stimulation of TLRs 3, 7, 9 also increased the secretion of polyreactive antibodies. Infection with a virus or tissue damage induced by a toxin similarly led to an increase in polyreactive antibodies in MyD88(+/+), but not MyD88(-/-) mice. We conclude that stimulation of TLRs is a key link in the mechanism of polyreactive antibody secretion into the circulation.


Plasma urate and serum deoxycytidylate deaminase measurements for the early diagnosis of pre-eclampsia.
The value of measuring plasma urate and serum deoxycytidylate deaminase (dCMP deaminase) for the early diagnosis of pre-eclampsia has been investigated in 45 patients. A combination of increased blood pressure and increased plasma urate identified 19 patients with a high incidence of fetal and maternal morbidity ascribable to pre-eclampsia. Seventeen of the 19 patients also had an increased serum dCMP deaminase. Serial antenatal observations for a mean period of 104 days (36-179 days) on 33 of the patients demonstrated that plasma urate and serum dCMP deaminase increased together as early changes in the development of pre-eclampsia. In six patients, blood pressure, plasma urate and serum dCMP deaminase all increased but in only one was the rise in blood pressure the first change. Elevations of plasma urate and serum dCMP deaminase are therefore both early features of pre-eclampsia. Serial measurements can give warning of the disorder before the appearance of other clinical features. The change in dCMP deaminase is probably another reflection of early renal involvement in the pre-eclamptic process.


Associations of proactive coping and self-efficacy with psychosocial outcomes in individuals after stroke.
To examine the associations of proactive coping and self-efficacy with psychosocial outcomes in individuals after stroke. Cross-sectional study. Regression analyses were performed. Outpatient settings of hospitals and rehabilitation centers. Individuals after stroke (N=112; mean age ± SD, 57.1±8.9y; mean time ± SD since stroke, 18.9±28.5mo). Not applicable. Proactive coping was measured using the Utrecht Proactive Coping Competence scale (UPCC), and self-efficacy was measured using the General Self-Efficacy Scale (GSES). Psychosocial outcomes were measured as (1) participation with the use of the restriction and satisfaction subscales of the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-Participation); (2) emotional problems with the use of the Hospital Anxiety and Depression Scale (HADS); (3) life satisfaction with the use of 2 questions (2LS); and (4) health-related quality of life (HRQOL) with the use of the Short Stroke-Specific Quality of Life scale (SS-QOL-12). Higher UPCC scores were associated with lower HADS scores (β=-.55, P<.001) and with higher USER-Participation satisfaction (β=.31, P=.001), 2LS (β=.34, P<.001), and SS-QOL-12 scores (β=.44, P<.001). The influence of UPCC scores on HRQOL was indirect through self-efficacy. Higher GSES scores were associated with higher UPCC scores (β=.65, P<.001), which in turn were associated with lower HADS scores (β=-.51, P<.001). GSES scores were directly associated with higher SS-QOL-12 scores (β=.32, P=.002). GSES scores did not influence the association between UPCC scores and any of the psychosocial outcomes (all P>.0025). Proactive coping and self-efficacy have different associations with each of the psychosocial outcomes. Therefore, outcome-specific models appear to be necessary to describe these associations.


[Prolonged mechanical ventilation probability model].
To design a probability model for prolonged mechanical ventilation (PMV) using variables obtained during the first 24 hours of the start of MV. An observational, prospective, multicenter cohort study. Thirteen Spanish medical-surgical intensive care units. Adult patients requiring mechanical ventilation for more than 24 hours. None. APACHE II, SOFA, demographic data, clinical data, reason for mechanical ventilation, comorbidity, and functional condition. A multivariate risk model was constructed. The model contemplated a dependent variable with three possible conditions: 1. Early mortality; 2. Early extubation; and 3. PMV. Of the 1661 included patients, 67.9% (n=1127) were men. Age: 62.1±16.2 years. APACHE II: 20.3±7.5. Total SOFA: 8.4±3.5. The APACHE II and SOFA scores were higher in patients ventilated for 7 or more days (p=0.04 and p=0.0001, respectively). Noninvasive ventilation failure was related to PMV (p=0.005). A multivariate model for the three above exposed outcomes was generated. The overall accuracy of the model in the training and validation sample was 0.763 (95%IC: 0.729-0.804) and 0.751 (95%IC: 0.672-0.816), respectively. The likelihood ratios (LRs) for early extubation, involving a cutoff point of 0.65, in the training sample were LR (+): 2.37 (95%CI: 1.77-3.19) and LR (-): 0.47 (95%CI: 0.41-0.55). The LRs for the early mortality model, for a cutoff point of 0.73, in the training sample, were LR (+): 2.64 (95%CI: 2.01-3.4) and LR (-): 0.39 (95%CI: 0.30-0.51). The proposed model could be a helpful tool in decision making. However, because of its moderate accuracy, it should be considered as a first approach, and the results should be corroborated by further studies involving larger samples and the use of standardized criteria.


Effects of chronic administration of benfluorex to rats on the metabolism of corticosterone, glucose, triacylglycerols, glycerol and fatty acid.
(1) Rats were fed on diets enriched with sucrose, beef tallow or corn oil and treated for 11-16 days with 50 mg of benfluorex per kg of body weight. By these times the growth rate and food intake were not significantly different from those of control rats. (2) Benfluorex approximately halved the concentration of circulating triacylglycerol in rats fed the beef tallow or sucrose diets. (3) It did not significantly alter the total lipoprotein lipase activity in diaphragm, heart and adipose tissue. (4) The clearance of triacylglycerols from chylomicrons exhibited two t 1/2 values of about 0.6 and 6.9 min in rats fed the beef tallow diet. Benfluorex did not significantly alter these values. (5) Benfluorex did not significantly alter the rate of appearance of triacylglycerol in the blood of rats injected with Triton WR 1339 to block triacylglycerol uptake. It did, however, decrease the rise in circulating glucose which presumably resulted from the stress of the procedure. (6) Benfluorex decreased the extent and duration of the rise in serum corticosterone when rats maintained on the corn oil diet were fed acutely with fructose. It also decreased the circulating concentrations of glycerol, triacylglycerol and glucose after fructose feeding. (7) Rats fed on the corn oil diet and then treated with benfluorex had lower concentrations of circulating glucose, triacylglycerol, glycerol and fatty acids after being injected with 2-deoxyglucose. (8) It is proposed that some of the long-term hypoglycaemic and hypotriglyceridaemic effects of benfluorex could be mediated indirectly through changes in endocrine balance, perhaps via the serotonergic system and in particular, by decreasing the effects of stress hormones relative to insulin. The implications of these findings are discussed in relation to controlling metabolism in stress conditions and for the management of obesity, diabetes and atherosclerosis.


Yeast LEU4 encodes mitochondrial and nonmitochondrial forms of alpha-isopropylmalate synthase.
The LEU4 gene of Saccharomyces cerevisiae is the major structural gene involved in the production of alpha-isopropylmalate synthase. It was recently proposed that LEU4 should be capable of encoding two forms of alpha-isopropylmalate synthase, based mainly on the observation that two of four major transcription start sites are located downstream from the ATG at the beginning of the LEU4 open reading frame (Beltzer, J. P., Chang, L. L., Hinkkanen, A. E., and Kohlhaw, G. B. (1986) J. Biol. Chem. 261, 5160-5167). The two forms with molecular weights of 68,000 and 65,000, respectively, would differ only in the N-terminal region, and only the larger of the two forms would be imported into the mitochondria. We have now constructed LEU4'-'lacZ translational fusion plasmids that contain either a normal LEU4' portion (expected to express both the long and the short forms of the fusion protein) or a modified LEU4' portion in which productive translation is possible only from the second in-frame AUG (expected to express only the short form of the fusion protein). beta-Galactosidase measurements and immunoblotting of crude mitochondrial and cytoplasmic fractions of yeast cells transformed with the fusion plasmids indicate that two forms of hybrid protein are produced and that only the larger form is targeted to the mitochondria. The distinguishing feature of the targeting sequence appears to be its ability to form an 18-residue long amphiphilic helix. Expression of the native short form of LEU4-encoded alpha-isopropylmalate synthase behind a strong yeast promoter has enabled us to show that the short form is functional in leucine biosynthesis, is inhibited by leucine with an apparent inhibitor constant of approximately 0.4 mM, and exists as a cytoplasmic dimer.


Oxidative stress: A common pathological state in a high-risk population for osteoporosis.
Osteoporosis is becoming a major concern in the field of public health. The process of bone loss is insidious and does not directly induce obvious symptoms. Complications indicate an irreversible decrease in bone mass. The high-risk populations of osteoporosis, including postmenopausal women, elderly men, diabetic patients and obese individuals need regular bone mineral density testing and appropriate preventive treatment. However, the primary changes in these populations are different, increasing the difficulty of effective treatment of osteoporosis. Determining the core pathogenesis of osteoporosis helps improve the efficiency and efficacy of treatment among these populations. Oxidative stress is a common pathological state secondary to estrogen deficiency, aging, hyperglycemia and hyperlipemia. In this review, we divided oxidative stress into the direct effect of reactive oxygen species (ROS) and the reduction of antioxidant enzyme activity to discuss their roles in the development of osteoporosis. ROS initiated mitochondrial apoptotic signaling and suppressed osteogenic marker expression to weaken osteogenesis. MAPK and NF-κB signaling pathways mediated the positive effect of ROS on osteoclast differentiation. Antioxidant enzymes not only eliminate the negative effects of ROS, but also directly participate in the regulation of bone metabolism. Additionally, we also described the roles of proinflammatory factors and HIF-1α under the pathophysiological changes of inflammation and hypoxia, which provided a supplement of oxidative stress-induced osteoporosis. In conclusion, our review showed that oxidative stress was a common pathological state in a high-risk population for osteoporosis. Targeted oxidative stress treatment would greatly optimize the therapeutic schedule of various osteoporosis treatments.


[Human bilharziasis in the Near-East Mediterranean countries. Historical aspects and current distribution].
The countries surrounding the mediterranean share geographical ethnic, historical and pathological features. Bilharziasis infectious found in these countries include S. haematobium infection in North Africa, Egypt and Near East and S. mansoni infection in Egypt and Arabian peninsula. The origin of two bilharziasis is probably West and East Africa, Egypt.


The Effect of Age, Postoperative Refraction, and Pre- and Postoperative Pupil Size on Halo Size and Intensity in Eyes Implanted with a Trifocal or Extended Depth-of-Focus Lens.
Halos are a chief source of patient dissatisfaction after multifocal intraocular lens (IOL) implantation. The primary purpose of this study was to investigate the influence of age, postoperative refraction, and pre- and postoperative pupil size on postoperative halo size with a trifocal diffractive IOL (AcrySof IQ PanOptix) and extended depth-of-focus (EDOF) IOL (TECNIS Symfony) to determine whether these factors could predict postoperative halo size. This single-center, open-label study conducted between October 2018 and April 2020 in Yokosuka, Japan included 160 patients: 80 with PanOptix and 80 with Symfony IOLs. Size and intensity of the halos were examined binocularly using a computer-based simulator (Eyeland Design Network GmbH) and scored from 0 (minimum) to 10 (maximum) at 1, 3, and 6 months postoperatively, along with the change in each variable for both IOLs. The respective correlations of halo size with age, postoperative refraction, pre- and postoperative pupil size, and discomfort level due to the halo were also investigated 6 months postoperatively. Halo size and intensity were significantly mitigated between 1, 3, and 6 months postoperatively. Throughout the observation period, halo size was significantly larger with PanOptix than with Symphony (P < 0.05), and halo intensity was significantly higher with Symphony than with PanOptix (P < 0.05). The pre- and postoperative pupil size correlated positively with halo size, while age and postoperative refraction were negatively correlated, for both IOLs. Understanding the features and predictive preoperative factors of halos in different types of multifocal IOLs may be useful in improving patient satisfaction.


MicroRNA 182 is a Novel Negative Regulator of Adipogenesis by Targeting CCAAT/Enhancer-Binding Protein α.
Recent studies have shown that microRNAs (miRNAs/miRs) play key roles in adipogenesis. This study aimed to investigate the role and underlying mechanism of miR-182 in adipogenesis. This study used the 3T3-L1 cell line and human visceral adipose tissue (VAT)-derived adipocytes to determine the role of miR-182 in adipogenesis. Adipose tissues from mice with high-fat diet-induced obesity, ob/ob mice, or human individuals with obesity were used to determine the association of miR-182 levels with obesity. A luciferase reporter assay was used to determine the target of miR-182. The expression level of miR-182 was greatly downregulated during white adipogenesis and markedly lower in the VAT of mice and humans with obesity. Ectopic expression of miR-182 in 3T3-L1 cells and human adipocytes suppressed the formation of lipid droplets and the expression of adipogenic genes. The luciferase reporter assay showed that miR-182 targeted the 3'-untranslated sequence of CCAAT/enhancer-binding protein α (C/EBPα) directly. In addition, glucocorticoids negatively regulated miR-182 expression, which, in turn, suppressed the glucocorticoid-induced expression of C/EBPα. Taken together, our studies identified miR-182 as a novel negative regulator of adipogenesis and a potential therapeutic target for obesity.