Model observer for assessing digital breast tomosynthesis for multi-lesion detection in the presence of anatomical noise.
Model observers are widely used in task-based assessments of medical image quality. The presence of multiple abnormalities in a single set of images, such as in multifocal multicentric breast cancer (MFMC), has an immense clinical impact on treatment planning and survival outcomes. Detecting multiple breast tumors is challenging as MFMC is relatively uncommon, and human observers do not know the number or locations of tumors a priori. Digital breast tomosynthesis (DBT), in which an x-ray beam sweeps over a limited angular range across the breast, has the potential to improve the detection of multiple tumors. However, prior studies of DBT image quality all focus on unifocal breast cancers. In this study, we extended our 2D multi-lesion (ML) channelized Hotelling observer (CHO) into a 3D ML-CHO that detects multiple lesions from volumetric imaging data. Then we employed the 3D ML-CHO to identify optimal DBT acquisition geometries for detection of MFMC. Digital breast phantoms with multiple embedded synthetic lesions were scanned by simulated DBT scanners of different geometries (wide/narrow angular span, different number of projections per scan) to simulate MFMC cases. With new implementations of 3D partial least squares (PLS) and modified Laguerre-Gauss (LG) channels, the 3D ML-CHO made detection decisions based upon the overall information from individual DBT slices and their correlations. Our evaluation results show that: (1) the 3D ML-CHO could achieve good detection performance with a small number of channels, and 3D PLS channels on average outperform the counterpart LG channels; (2) incorporating locally varying anatomical backgrounds and their correlations as in the 3D ML-CHO is essential for multi-lesion detection; (3) the most effective DBT geometry for detection of MFMC may vary when the task of clinical interest changes, and a given DBT geometry may not yield images that are equally informative for detecting MF, MC, and unifocal cancers.


alpha-ketoglutaric semialdehyde dehydrogenase isozymes involved in metabolic pathways of D-glucarate, D-galactarate, and hydroxy-L-proline. Molecular and metabolic convergent evolution.
Azospirillum brasilense possesses an alternative pathway of l-arabinose metabolism in which alpha-ketoglutaric semialdehyde (alphaKGSA) dehydrogenase (KGSADH) is involved in the last step, the conversion of alphaKGSA to alpha-ketoglutarate. In the preceding studies, we identified a set of metabolic genes of the l-arabinose pathway including the KGSADH gene (Watanabe, S., Kodaki, T., and Makino, K. (2006) J. Biol. Chem. 281, 2612-2623; Watanabe, S., Kodaki, T., and Makino, K. (2006) J. Biol. Chem. 281, 28876-28888; Watanabe, S., Shimada, N., Tajima, K., Kodaki, T., and Makino, K. (2006) J. Biol. Chem. 281, 33521-33536). Here, we describe that A. brasilense possesses two different KGSADH isozymes from l-arabinose-related enzyme (KGSADH-I); that is, d-glucarate/d-galactarate-inducible KGSADH-II and hydroxy-l-proline-inducible KGSADH-III. They were purified homogeneously from A. brasilense cells grown on d-galactarate or hydroxy-l-proline, respectively. When compared with KGSADH-I, amino acid sequences of KGSADH-II and KGSADH-III were significantly similar but not totally identical. Physiological characterization using recombinant enzymes revealed that KGSADH-II and KGSADH-III showed similar high substrate specificity for alphaKGSA and different coenzyme specificity; that is, NAD(+)-dependent KGSADH-II and NADP(+)-dependent KGSADH-III. In the phylogenetic tree of the aldehyde dehydrogenase (ALDH) superfamily, KGSADH-II and KGSADH-III were poorly related to the known ALDH subclasses including KGSADH-I. On the other hand, ALDH-like ycbD protein involved in d-glucarate/d-galactarate operon from Bacillus subtilis is closely related to the methylmalonyl semialdehyde dehydrogenase subclass but not A. brasilense KGSADH isozymes. To estimate the correct function, the corresponding gene was expressed, purified, and characterized. Kinetic analysis revealed the physiological role as NADP(+)-dependent KGSADH. We conclude that three different types of KGSADH appeared in the bacterial evolutional stage convergently. Furthermore, even the same pathway such as l-arabinose and d-glucarate/d-galactarate metabolism also evolved by the independent involvement of KGSADH.


Between a Camera and a Hard Place: A Content Analysis of Performer Representation in Heterosexual Pornographic Content.
This study examined the physical representation of men and women in online pornography through a content analysis. A total of 123 popular pornographic Internet videos featuring a male-female dyad were gathered from the most visited pornographic website in the United States. Coders analyzed the screen time, visual, and audible presence of each actor within a sexual scene. Female performers were substantially more physically represented on screen, based on an operational definition of representation that included screen time, on-screen placement, camera blocking techniques, intelligible and unintelligible audibility, and participation with the camera. Female performers were found to be physically represented on screen over four times as much as male performers. Results are discussed in terms of their implications for understanding viewers' formation of sexual behaviors, attitudes, and beliefs, to the extent that these formations are influenced, at least in part, by the physical representation of characters within a pornography scene.


Calibration of equipment for analysis of drinking water fluoride: a comparison study.
Current American Dental Association evidence-based recommendations for prescription of dietary fluoride supplements are based in part on the fluoride concentration of a pediatric patient's drinking water. With these recommendations in mind, this study compared the relative accuracy of fluoride concentration analysis when a common apparatus is calibrated with different combinations of standard values. Fluoride solutions in increments of 0.1 ppm, from a range of 0.1 to 1.0 ppm fluoride, as well as 2.0 and 4.0 ppm, were gravimetrically prepared and fluoride concentration measured in pentad, using a fluoride ion-specific electrode and millivolt meter. Fluoride concentrations of these solutions were recorded after calibration with the following 3 different combinations of standard fluoride solutions: 0.1 ppm and 0.5 ppm, 0.1 ppm and 1.0 ppm, 0.5 ppm and 1.0 ppm. Statistical analysis showed significant differences in the fluoride content of water samples obtained with different two-standard fluoride solutions. Among the two-standard fluoride solutions tested, using 0.5 ppm and 1.0 ppm as two-standard fluoride solutions provided the most accurate fluoride measurement of water samples containing fluoride in the range of 0.1 ppm to 4.0 ppm. This information should be valuable to dental clinics or laboratories in fluoride analysis of drinking water samples.


The place of amputation in the management of the ischaemic lower limb in the dysvascular geriatric patient.
Statistics show that today the majority of amputations of the leg are peripheral vascular disease in patients over the age of 60. The stages of management are discussed and in particular a plea made for taking a balanced view of vascular salvage procedure and amputation as alternative treatments. The advantages are stressed for these patients to be treated in a unit where the resources for appropriate investigation are available and the surgeon has the support of a multi-disciplinary team. The importance of the pre- and post-amputation rehabilitation programme is discussed.


Operative treatment of isolated greater tuberosity fractures: retrospective review of clinical and functional outcomes.
Displaced isolated greater tuberosity fractures are rare injuries that require operative treatment to optimize rotator cuff function and prevent painful subacromial impingement. A lack of consensus exists regarding ideal management of these injuries because of the paucity of literature on the subject.The outcomes of 17 patients treated with open (n=15) or arthroscopic (n=2) fixation at the authors' institution between 2001 and 2009 were retrospectively reviewed. Postoperative range of motion, American Shoulder and Elbow Surgeons (ASES) score, visual analog scale (VAS) score, and overall patient satisfaction were recorded at final follow-up. At a mean of 5.2 years (range 1.5-9.7 years), average postoperative active forward elevation was 150.3° (range, 60°-180°), ASES score was 82.9 (range, 46.7-100), and VAS score was 1.4 (range, 0-5). According to Neer's criteria, the overall outcome was excellent in 11 (65%) patients, satisfactory in 5 (29%) patients, and unsatisfactory in 1 (6%) patient. Final postoperative radiographs were available for 15 patients at a mean of 6.64 months. Radiographic union with near-anatomic position of the greater tuberosity was achieved in 13 (87%) of 15 patients. The presence of rotator cuff and rotator interval tears requiring repair, history of dislocation, age 60 years or older, and delayed time to surgery ≥ 10 days did not significantly (P>.05) influence the patients' final active forward elevation and ASES scores.Favorable patient outcomes can be achieved when fractures with >5 mm of displacement are treated with anatomic reduction and secure fixation. For a specific injury, the ideal surgical approach and method of fixation is dictated by patient characteristics and fracture pattern.


Synthesis and aggregation behaviour of single-chain, 1,32-alkyl-branched bis(phosphocholines) - part 2: lateral chain length triggers self-assembling from sheets to fibres to vesicles.
Six single-chain, 1,32-alkyl-branched bis(phosphocholines) PC-C32(1,32Cm)-PC have been synthesized as model lipids for naturally occurring archaeal membrane lipids. The preparation of these bipolar amphiphiles bearing lateral alkyl chains of different lengths (C4-C15) was realized using a Cu-catalyzed Grignard bis-coupling reaction of various primary alkyl-branched bromides as side parts and a 1,22-dibromide as the centre part. The aggregation behaviour of these bolalipids in water was initially investigated by differential scanning calorimetry and transmission electron microscopy. As a main result, the types of aggregates found and their stability upon heating were strongly connected to the length of the lateral alkyl chain of the bolalipid: short and long lateral chains led to lamellar structures, whereas side chains of medium length led to fibrous aggregates. In future, these bolalipids could be used to produce tailored and stabilized liposomes for oral drug delivery.


Analytic hyperpolarizability and polarizability derivative with fractional occupation numbers for large extended systems.
The analytic hyperpolarizability and polarizability derivative with fractional occupation numbers are derived using Wigner's 2n + 1 rule. The formulation contains no terms that blow up for quasi-degenerate systems. The density-functional tight-binding method is used for implementation, which makes it possible to compute these third-order derivatives for systems containing up to one thousand atoms within 8 h using 24 CPU cores. A comparison between analytic and numerical non-resonance Raman activity spectra indicates that the numerical differentiation approach can give a significant deviation unless the strength of perturbative electric field is carefully chosen. With extremely high electronic temperatures, the polarizability and hyperpolarizability should converge to zero.


Synthesis and biological properties of 2-hydroxy-1-(1-phenyltetralyl)piperidine and some of its intermediates as derivatives of phencyclidine.
Phencyclidine (1-(1-phenylcyclohexyl)piperidine, CAS 956-90-1, PCP) has shown analgesic effects. Some of its derivatives were synthesized and their biological properties were studied. To date, only saturated ketones have been used as starting materials for synthesizing the phencyclidine family. In order to show desirable biological activity, the aromatic and piperidine rings are necessary for these compounds. Using alpha-tetralone as a starting material, 2-hydroxy-1-(-phenyltetralyl)piperidine, an analogue of the phencyclidine family, and some of its intermediates were synthesized. This ketone was reacted with phenyl magnesium bromide and the resultant alcohol was reacted with acetic anhydride to give alkene that was treated with potassium permanganate to give diol. This compound was treated with a suspension of sodium azide and trichloroacetic acid to give the azide compound that was reduced with LiAlH4 to give the primary amine. Cyclization of this compound with 1,5-dibromopentane finally gave a tertiary amine. It is predicted that the title compound 2-hydroxy-1-(1-phenyltetralyl)piperidine exerts a potent analgesic effect on acute and phasic pain.


Hydrodissection of Wiltse's Plane to Facilitate Exposure During Minimally Invasive Transforaminal Lumbar Interbody Fusion.
Traditional posterior lumbar approaches in a transforaminal lumbar interbody fusion (TLIF) require subperiosteal dissection of bilateral paraspinal muscles to provide adequate exposure. This may traumatize the multifidus muscle and its afferent innervations leading to postoperative paraspinal muscle atrophy. Minimizing such intraoperative trauma has been identified as an important factor in the reduction of postoperative lumbar pain. An approach via a blunt dissection through Wiltse's plane, which lies between the longissimus and multifidus muscles, may minimize postoperative pain. Definition of this plane may be facilitated by local injection of 1% lidocaine within the plane itself, as well as in the musculature defining its borders. In this paper, we demonstrate this technique with a 55-year-old female patient who presented with left-sided radicular leg pain in an L5 distribution. Wiltse plane hydrodissection was utilized in performing an L4-5 TLIF. Ultrasound images of the patient's sub-fascial musculature were obtained pre- and posthydrodissection to assess the elucidation of this plane through this technique. Intraoperative images were obtained following dissection of Wiltse's plane to further illustrate the facilitation of exposure of Wiltse's plane through hydrodissection. Postoperatively the patient did well citing a complete resolution of her radicular pain. She did not require intravenous (IV) pain medication, as her postoperative pain was well controlled with oral pain medication. She was mobilized on post-op day one, and discharged home on post-op day two with minimal back pain. Our initial experience supports the feasibility, safety, and effectiveness of hydrodissection of Wiltse's plane to facilitate exposure during a minimally invasive TLIF and thereby reducing postoperative pain.


Serum Amyloid A 4 as a Common Marker of Persistent Inflammation in Patients with Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.
Neovascular age-related macular degeneration (nAMD) and its subtype, polypoidal choroidal vasculopathy (PCV), are common choroidal vasculopathies. Although they share many common clinical manifestations and treatment strategies, a lack of comprehensive analysis of these conditions means that it is difficult for researchers to further explore the common pathomechanisms of nAMD and PCV. The aim of this study was to characterize aqueous humor (AH) proteome alterations and identify a novel biomarker related to both nAMD and PCV. Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) was adopted to analyze the AH proteomes of nAMD, PCV and controls. The target protein was validated using the enzyme-linked immunosorbent assay (ELISA) and subjected to receiver operating characteristic (ROC) curve analysis. A total of 737 different proteins were identified in all the groups, of which 544 were quantifiable. The bioinformatics analysis suggested that immune response activation is the essential event in both nAMD and PCV. Serum amyloid A (SAA) 4 is closely associated with a number of chronic inflammatory diseases, and it was enriched as the hub protein. ROC analysis showed that SAA4 could distinguish both nAMD and PCV from the controls. This comprehensive study provides insights into, and furthers our understanding of, the pathological mechanism of nAMD and PCV. Additionally, the SAA4 level alteration may serve as a common biomarker of nAMD and PCV.


Colour-blind racial attitudes in entry-level dental hygiene students in Virginia.
Subscribing to colour-blind racial attitudes may contribute to inequities in the delivery of oral care and affect treatment of diverse patients. The purpose of this study was to survey all entry-level dental hygiene students in one state to determine colour-blind racial attitudes. After IRB approval, a convenience sample of 220 dental hygiene students in all entry-level programmes in Virginia were invited to participate in this cross-sectional study. The Colour-Blind Racial Attitudes Scale (CoBRAS), an effective, validated measuring instrument, was used to quantify unawareness of contemporary racist ideals. Three subscales (Racial Privilege, Institutional Discrimination and Blatant Racial Issues) were also measured by the survey. Descriptive statistics, separate one-way between-subjects ANOVA and independent samples t-tests were used to analyse the data. One-hundred and sixty (n = 160) dental hygiene students completed the survey. Independent samples t-tests revealed statistically significant differences when comparing year in programme and programme type. Participants in their second year of dental hygiene education had significantly lower overall CoBRAS scores compared to those in their first year of education (M = 50.76, M = 59.13, respectively; p = 0.004). Participants enrolled in a baccalaureate dental hygiene (B.S.) programme had significantly lower overall CoBRAS scores compared to those enrolled in an associate (A.S.) programme (M = 50.53, M = 59.54, respectively; p = 0.002). Participants possessed moderate levels of colour-blindness, suggesting a need for more awareness and training early in dental hygiene education to increase delivery of culturally competent oral healthcare.


Effects of various immunosuppressive drugs on the development of experimental renal infection in rats.
The effect of azathioprine, hydrocortisone and antihymocyte serum on the development of experimental colibacillary renal infection in rats was assessed by macroscopical findings in the kidneys, especially by determining the number of microbes in the infected organ, on day 7 after injection of the infectious agent. The greatest multiplication of bacteria and so the most pronounced macroscopical changes occurred after ALS treatment. There was statistically significant difference between ALS-treated group and the control group, whereas the differences between controls and the other experimental groups (Imuran, hydrocortisone) were non-significant.


Eomesodermin promotes the development of type 1 regulatory T (TR1) cells.
Type 1 regulatory T (TR1) cells are Foxp3- interleukin-10 (IL-10)-producing CD4+ T cells with potent immunosuppressive properties, but their requirements for lineage development have remained elusive. We show that TR1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes), and are critical for the prevention of graft-versus-host disease. We demonstrate that Eomes is required for TR1 cell differentiation, during which it acts in concert with the transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other T helper cell lineages. We further show that Eomes induction in TR1 cells requires T-bet and donor macrophage-derived IL-27. Thus, we define the cellular and transcriptional control of TR1 cell differentiation during BMT, opening new avenues to therapeutic manipulation.


Importance of Gly-13 for the coenzyme binding of human UDP-glucose dehydrogenase.
UDP-glucose dehydrogenase (UGDH) is the unique pathway enzyme furnishing in vertebrates UDP-glucuronate for numerous transferases. In this report, we have identified an NAD(+)-binding site within human UGDH by photoaffinity labeling with a specific probe, [(32)P]nicotinamide 2-azidoadenosine dinucleotide (2N(3) NAD(+)), and cassette mutagenesis. For this work, we have chemically synthesized a 1509-base pair gene encoding human UGDH and expressed it in Escherichia coli as a soluble protein. Photolabel-containing peptides were generated by photolysis followed by tryptic digestion and isolated using the phosphopeptide isolation kit. Photolabeling of these peptides was effectively prevented by the presence of NAD(+) during photolysis, demonstrating a selectivity of the photoprobe for the NAD(+)-binding site. Amino acid sequencing and compositional analysis identified the NAD(+)-binding site of UGDH as the region containing the sequence ICCIGAXYVGGPT, corresponding to Ile-7 through Thr-19 of the amino acid sequence of human UGDH. The unidentified residue, X, can be designated as a photolabeled Gly-13 because the sequences including the glycine residue in question have a complete identity with those of other UGDH species known. The importance of Gly-13 residue in the binding of NAD(+) was further examined with a G13E mutant by cassette mutagenesis. The mutagenesis at Gly-13 had no effects on the expression or stability of the mutant. Enzyme activity of the G13E point mutant was not measurable under normal assay conditions, suggesting an important role for the Gly-13 residue. No incorporation of [(32)P]2N(3)NAD(+) was observed for the G13E mutant. These results indicate that Gly-13 plays an important role for efficient binding of NAD(+) to human UGDH.


Intrafamilial phenotypic variation in spinocerebellar ataxia type 23.
Spinocerebellar ataxia type 23 (SCA23) is an autosomal dominant cerebellar ataxia caused by pathogenic variants in the prodynorphin gene (PDYN). The frequency of PDYN variants is reportedly very low (~ 0.1%) in several ataxia cohorts screened to date. We found five cases of SCA23 in two families (mean age at onset: 37.8 ± 5.5 years; mean age at examination: 64.2 ± 12.3 years) with a novel PDYN variant (c.644G > A:p.R215H). We identified marked heterogeneity in the clinical features in Family 1: the proband showed clinical and neuroimaging features suggestive of multiple system atrophy with predominant parkinsonism (MSA-P). Conversely, the proband's mother with the PDYN p.R215H variant had no subjective symptoms; she had not come to medical attention before our survey, although she showed apparent cerebellar atrophy on brain magnetic resonance imaging (MRI). The other two patients in Family 1 and a patient in Family 2 showed slowly progressive cerebellar ataxia. We here report two Japanese families with SCA23, one of which showed considerable phenotypic variation in affected members. Our findings support that SCA23 can phenotypically overlap with MSA.


Hepatic artery infusion with raltitrexed or 5-fluorouracil for colorectal cancer liver metastasis.
To evaluate the efficiency and safety of hepatic artery infusion chemotherapy (HAIC) using raltitrexed or 5-fluorouracil for colorectal cancer (CRC) liver metastasis (CRCLM). A retrospective analysis of patients with unresectable CRCLM who failed systemic chemotherapy and were subsequently treated with HAIC at our institute from May 2013 to April 2015 was performed. A total of 24 patients were treated with 5-fluorouracil, and 18 patients were treated with raltitrexed. The median survival time (MST) from diagnosis of CRC was 40.8 mo in the oxaliplatin plus raltitrexed (TOMOX) arm and 33.5 mo in the oxaliplatin plus 5-fluorouracil (FOLFOX) arm (P = 0.802). MST from first HAIC was 20.6 mo in the TOMOX arm and 15.4 mo in the FOLFOX arm (P = 0.734). Median progression-free survival (PFS) from first HAIC was 4.9 mo and 6.6 mo, respectively, in the TOMOX arm and FOLFOX arm (P = 0.215). Leukopenia (P = 0.026) was more common in the FOLFOX arm, and hepatic disorder (P = 0.039) was more common in the TOMOX arm. There were no treatment-related deaths in the TOMOX arm and one treatment-related death in the FOLFOX arm. Analysis of prognostic factors indicated that response to HAIC was a significant factor related to survival. No significant difference in survival was observed between the TOMOX and FOLFOX arms. HAIC treatment with either TOMOX or FOLFOX was demonstrated as an efficient and safe alternative choice.


Methylenetetrahydrofolate reductase polymorphism in the etiology of Down syndrome.
A methylenetetrahydrofolate reductase polymorphism (677 C/T mutation) was recently implicated in the etiology of Down syndrome. We studied a cohort of 85 women carrying fetuses with Down syndrome and found no difference in the frequencies of the three groups of subjects (C/C, C/T, T/T) between Down syndrome mothers and controls.


Updating the elite rice variety Kongyu 131 by improving the Gn1a locus.
Kongyu 131 is an elite japonica rice variety of Heilongjiang Province, China. It has the characteristics of early maturity, superior quality, high yield, cold tolerance and wide adaptability. However, there is potential to improve the yield of Kongyu 131 because of the relatively few grains per panicle compared with other varieties. Hence, we rebuilt the genome of Kongyu 131 by replacing the GRAIN NUMBER1a (Gn1a) locus with a high-yielding allele from a big panicle indica rice variety, GKBR. High-resolution melting (HRM) analysis was used for single nucleotide polymorphism (SNP) genotyping. Quantitative trait locus (QTL) analysis of the BC3F2 population showed that the introgressed segment carrying the Gn1a allele of GKBR significantly increased the branch number and grain number per panicle. Using 5 SNP markers designed against the sequence within and around Gn1a, the introgressed chromosome segment was shortened to approximately 430 Kb to minimize the linkage drag by screening recombinants in the target region. Genomic components of the new Kongyu 131 were detected using 220 SNP markers evenly distributed across 12 chromosomes, suggesting that the recovery ratio of the recurrent parent genome (RRPG) was 99.89%. Compared with Kongyu 131, the yield per plant of the new Kongyu 131 increased by 8.3% and 11.9% at Changchun and Jiamusi, respectively. To achieve the high yield potential of Kongyu 131, a minute chromosome fragment carrying the favorable Gn1a allele from the donor parent was introgressed into the genome of Kongyu 131, which resulted in a larger panicle and subsequent yield increase in the new Kongyu 131. These results indicate the feasibility of improving an undesirable trait of an elite variety by replacing only a small chromosome segment carrying a favorable allele.


Treatment of aggressive prolactinoma with temozolomide: A case report and review of literature up to date.
Aggressive pituitary adenomas and pituitary carcinomas are rare and demand multiple treatment strategies. Temozolomide, an orally active alkylating chemotherapeutic agent, has recently been recommended as a salvage medication for refractory pituitary adenomas or carcinomas. A 17-year-old male presenting with aggressive prolactinoma that continued to progress despite surgery, gamma knife, and dopamine agonists. The diagnosis of refractory aggressive prolactinoma was made on the basis of clinical findings and the lack of efficacy of conventional treatment. The patient received the most frequently recommended regimen of temozolomide treatment for 22 cycles. Temozolomide resulted in a remarkable shrinkage of tumor mass and inhibition of prolactin secretion and this patient's clinical condition improved progressively. Temozolomide can be used as a salvage treatment to refractory pituitary tumors and o(6)-methylguanine-DNA methyltransferase (MGMT) status is a significant predictor to the effectiveness of temozolomide based on the existing literature.


Co-existence of NDM-, aminoglycoside- and fluoroquinolone-resistant genes in carbapenem-resistant Escherichia coli clinical isolates from Pakistan.
Background: To determine the prevalence of antimicrobial-resistant genes in carbapenem-resistant Escherichia coli (CRECO). Methods: A total of 290 carbapenem-resistant bacteria were collected from tertiary care hospitals in Lahore (Pakistan). These isolates were confirmed by VITEK 2 and matrix-assisted laser desorption/ionization time of flight. The minimum inhibitory concentration was performed by VITEK 2. Sequence typing, resistant gene identification, DNA hybridization and replicate typing were also performed. Results: 33 out of 290 (11.3%) were CRECO and carried blaNDM; 69, 18 and 12% were NDM-1, NDM-5 and NDM-7, respectively, with 100% resistance to β-lactams and β-lactam inhibitors. ST405 and ST468 were mostly identified. NDM-ECO carried approximately 50-450 kb of plasmids and 16 (55%) were associated with IncA/C. Conclusion: NDM-1-producing E. coli are highly prevalent in clinical settings.


Smad7 inhibits fibrotic effect of TGF-Beta on renal tubular epithelial cells by blocking Smad2 activation.
It has been shown that transforming growth factor-beta (TGF-beta) is a potent mediator in renal fibrosis and that Smad proteins are critical intracellular mediators in TGF-beta signaling. It is here reported that TGF-beta mediates renal fibrogenesis in tubular epithelial cells (TEC) in association with the activation of Smad2 and that overexpression of Smad7 blocks this fibrotic process. Using a normal rat kidney tubular epithelial cell line (NRK52E), it was determined that TGF-beta1 induces Smad2 phosphorylation and nuclear localization in both a dose- and time-dependent manner. The activation of Smad2 was evident at 5 min (20%), peaked at 15 to 30 min (85%), and declined to baseline levels by 2 h (5 to 10%). This was associated with de novo expression of collagens I, III, and IV and the transformation of TEC into a "myofibroblast" phenotype with de novo expression of alpha-smooth muscle actin (alpha-SMA) and with the loss of E-cadherin (>50%). To investigate a negative regulatory role of Smad7 in renal fibrosis, the Smad 7 gene was stably transfected and its expression was tightly controlled by doxycycline into NRK52E cells. Overexpression of Smad7 induced by doxycycline results in marked inhibition of TGF-beta-induced Smad2 activation (90% downward arrow) with the prevention of collagen synthesis and myofibroblast transformation. Thus, Smad2 activation occurs in the fibrogenic response of TEC to TGF-beta, and this process is blocked by overexpression of Smad7. This indicates that Smad signaling is a key pathway of TGF-beta-mediated renal fibrosis and suggests that treatments targeting the inactivation of Smad2 by overexpression of Smad7 may provide a new therapeutic strategy for renal fibrosis.


Interaction between hepatitis B virus and SARS-CoV-2 infections.
Coronavirus disease 2019 (COVID-19) has become a global pandemic and garnered international attention. The causative pathogen of COVID-19 is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel, highly contagious coronavirus. Numerous studies have reported that liver injury is quite common in patients with COVID-19. Hepatitis B has a worldwide distribution as well as in China. At present, hepatitis B virus (HBV) remains a leading cause of cirrhosis, liver failure, and hepatocellular carcinoma. Because both viruses challenge liver physiology, it raises questions as to how coinfection with HBV and SARS-CoV-2 affect disease progression and mortality. Is there an increased risk of COVID-19 in patients with HBV infection? In this review, we summarize the current reports of SARS-CoV-2 and HBV coinfection and elaborate the interaction of the two diseases. The emphasis was placed on evaluating the impact of HBV infection on disease severity and clinical outcomes in patients with COVID-19 and discussing the potential mechanism behind this effect.


Dextrose gel treatment does not impair subsequent feeding.
Dextrose gel is increasingly used as first-line treatment for neonatal hypoglycaemia. Treatment with 400 mg/kg previously has been reported to impair subsequent feeding. We sought to determine if the recommended dose of 200 mg/kg altered feeding. Hypoglycaemic babies were randomised to 200 mg/kg dextrose gel or placebo and fed. Prefeed alertness, quality and duration of breast feeding, and the volume of formula taken were assessed on the next feeding. Prefeed alertness scores were similar in babies (n=211) treated with dextrose or placebo gel (124 episodes, OR=1.30 (95% CI 0.62 to 2.77), p=0.49). Breastfed babies were more likely to have good feeding scores after dextrose gel (160 episodes, OR=3.54 (95% CI 1.30 to 9.67), p=0.01) but similar breastfeeding duration (57 episodes, median (range) 20 (3-90) vs 25 (2-80) min, p=0.62). Formula volumes taken were also similar (24 episodes, median (range) 4.6 (2.2-11.3) vs 6.4 (2.0-8.9) mL/kg, p=0.30). Treating hypoglycaemic babies with dextrose gel 200 mg/kg does not depress subsequent feeding and may improve breastfeeding quality. ACTRN 12608000623392.


Penile injection of aedile silicone: A dangerous shortcut.
The size of penis can cause concern in patients, even if the organ is clinically normal. Additionally, the cost of phosphodiesterase 5 inhibitors (iPDE5) and long waiting lists to access penile prosthesis placement can lead patients to resort to non-medical and potentially dangerous alternatives. One of these dangerous alternatives is the injection of building silicone at the level of the subcutis of the penis or the corpora cavernosa causing the formation of a granuloma that increases the girth and consistency of the penis. The article describes the case of a 43-year-old patient who self-injected aedile silicone at the level of his penis in an attempt to achieve greater penile size and greater rigidity. The patient reported that he could not economically afford the iPDE5.The persistence of severe pain in the penis forced the patient to go to a urological examination. The patient subsequently underwent the penile granuloma exeresis procedure and skin reconstruction with scrotal flap. The pursuit of sexual well-being can lead some patients to rely on unconventional and potentially harmful techniques. The role of the andrologist and of the scientific society should be to dissuade the patient from using these dangerous methods and to provide valid alternatives accessible to the patient. The economic difficulty in purchasing drugs that facilitate erection or the long waiting lists for the placement of penile prostheses can favor dangerous methods such as penile injection of silicon. There is therefore a clear need to facilitate access to drugs and surgical techniques that favor the patient's sexual well-being.


Proposed New Dynamic Prognostic Index for Diffuse Large B-Cell Lymphoma: International Metabolic Prognostic Index.
Baseline metabolic tumor volume (MTV) is a promising biomarker in diffuse large B-cell lymphoma (DLBCL). Our aims were to determine the best statistical relationship between MTV and survival and to compare MTV with the International Prognostic Index (IPI) and its individual components to derive the best prognostic model. PET scans and clinical data were included from five published studies in newly diagnosed diffuse large B-cell lymphoma. Transformations of MTV were compared with the primary end points of 3-year progression-free survival (PFS) and overall survival (OS) to derive the best relationship for further analyses. MTV was compared with IPI categories and individual components to derive the best model. Patients were grouped into three groups for survival analysis using Kaplan-Meier analysis; 10% at highest risk, 30% intermediate risk, and 60% lowest risk, corresponding with expected clinical outcome. Validation of the best model was performed using four studies as a test set and the fifth study for validation and repeated five times. The best relationship for MTV and survival was a linear spline model with one knot located at the median MTV value of 307.9 cm3. MTV was a better predictor than IPI for PFS and OS. The best model combined MTV with age as continuous variables and individual stage as I-IV. The MTV-age-stage model performed better than IPI and was also better at defining a high-risk group (3-year PFS 46.3% v 58.0% and 3-year OS 51.5% v 66.4% for the new model and IPI, respectively). A regression formula was derived to estimate individual patient survival probabilities. A new prognostic index is proposed using MTV, age, and stage, which outperforms IPI and enables individualized estimates of patient outcome.


Overexpression of microRNA-620 facilitates the resistance of triple negative breast cancer cells to gemcitabine treatment by targeting DCTD.
Patients with triple negative breast cancer (TNBC) have a poor survival rate following chemotherapy due to drug resistance. Notably, the molecular mechanism of drug resistance remains elusive. Between December 2011 and December 2014, 36 TNBC samples were obtained from Liaocheng People's Hospital. Three gemcitabine-resistant MDA-MB-231 cell lines (MDA-MB-231rGEM1, MDA-MB-231rGEM2 and MDA-MB-231rGEM3) were obtained by exposure of MDA-MB-231 cells to increasing concentrations of gemcitabine for >12 months. Reverse transcription-quantitative polymerase chain reaction was performed to detect the expression levels of specific genes, including microRNA (miR)-620, ATP-binding cassette sub-family B member 1 (ABCB1), ABCC10, cytidine monophosphate kinase, deoxycytidine monophosphate deaminase (DCTD), nucleoside diphosphate kinase 1 (NME1), ribonucleoside-diphosphate reductase large subunit (RRM1) and RRMB2. Western blot analysis was performed to assess the protein expression levels of DCTD. Furthermore, cell proliferation was assessed using a Cell Counting Kit-8 assay and cell apoptosis was detected using an Annexin V/Dead Cell Apoptosis kit. Interactions between miR-620 and DCTD were predicted using TargetScan and detected with the dual luciferase reporter assay. Elevation of miR-620 expression levels were detected in two of the assessed gemcitabine-resistant MDA-MB-231 cell lines compared with MDA-MB-231 cells. Gemcitabine induced significant elevation of miR-620 in MDA-MB-231 cells. An increase of DCTD at mRNA and protein expression levels in MDA-MB-231rGEM1 cells was observed compared with those in MDA-MB-231 cells. Results suggested that DCTD was directly regulated by miR-620. Inhibition of miR-620 and overexpression of DCTD reversed gemcitabine resistance in MDA-MB-231rGEM1 cells via inducing cell apoptosis and cell growth arrest. A negative correlation was identified between miR-620 and DCTD mRNA expression levels in patients with TNBC. The present results demonstrated that overexpression of miR-620 could contribute to the development of gemcitabine resistance in patients with TNBC via the direct downregulation of DCTD.


Reassessment of cochlear dead regions in hearing-impaired teenagers with severe-to-profound hearing loss.
The aim of this study was to reassess cochlear dead regions after an interval of twelve months, using the Threshold Equalising Noise (TEN) test. Thirty-four ears of 24 teenagers (mean age of 14 years) with longstanding severe-to-profound sensorineural hearing impairment were tested. Testing was repeated after an interval of 12 months using the same experimental set-up. A total of eight (23.5%) out of 34 ears changed category on retest: this decreased to two (7.1%) out of 27 ears when the inconclusive category was removed from the analysis. In both of these ears (of the same participant) the criteria were met at a single frequency, and the masked threshold was only 10 dB above the TEN level per ERBN. When all of the data were examined on a frequency-by-frequency basis, the instances that changed category ranged from 15 to 51%. The range decreased to between 4 and 34% when the inconclusive category was removed from the analysis.


[Performance evaluation of CT automatic exposure control on fast dual spiral scan].
The performance of individual computed tomography automatic exposure control (CT-AEC) is very important for radiation dose reduction and image quality equalization in CT examinations. The purpose of this study was to evaluate the performance of CT-AEC in conventional pitch mode (Normal spiral) and fast dual spiral scan (Flash spiral) in a 128-slice dual-source CT scanner. To evaluate the response properties of CT-AEC in the 128-slice DSCT scanner, a chest phantom was placed on the patient table and was fixed at the center of the field of view (FOV). The phantom scan was performed using Normal spiral and Flash spiral scanning. We measured the effective tube current time product (Eff. mAs) of simulated organs in the chest phantom along the longitudinal (z) direction, and the dose dependence (distribution) of in-plane locations for the respective scan modes was also evaluated by using a 100-mm-long pencil-type ionization chamber. The dose length product (DLP) was evaluated using the value displayed on the console after scanning. It was revealed that the response properties of CT-AEC in Normal spiral scanning depend on the respective pitches and Flash spiral scanning is independent of the respective pitches. In-plane radiation dose of Flash spiral was lower than that of Normal spiral. The DLP values showed a difference of approximately 1.7 times at the maximum. The results of our experiments provide information for adjustments for appropriate scanning parameters using CT-AEC in a 128-slice DSCT scanner.


Potential loss of phosphorus from a rice field in Taihu Lake basin.
Nonpoint-source pollution by phosphorus (P) poses a threat to waters in the Taihu Lake basin in China. The potential transfer of P in rice (Oryza sativa L.) fields through surface drainage and subsurface flow was investigated under simulated conventional irrigation-drainage management. Surface drainage events were conducted to avoid overflow across the plots after heavy rainfall and for rice harvest, at which time P losses were also investigated. This study was conducted in 2001 in a long-term rice field experiment. The experimental plots were treated with 0, 26, or 52 kg P ha(-1) as superphosphate or 26 kg P ha(-1) with equal parts of P supplied as superphosphate and pig manure. Phosphorus concentrations and loads in field floodwater on plots receiving P rapidly declined in a nonlinear manner before the first drainage, three weeks after fertilizer application. The combined application of fertilizer and manure P resulted in higher P transfer potential in field floodwater than with fertilizer P alone one week after P application. Phosphorus concentrations in interflow water sampled by Teflon suction cups inserted at a depth of 150 to 200 mm gradually increased within two weeks after P application, then declined. The concentration of P in interflow water was related to soil P buildup from long-term P application, as well as recently applied P. The 26 kg P ha(-1) treatment (the conventional P rate in this region) resulted in a loss of 0.74 kg total phosphorus (TP) ha(-1) and a drainage-weighted average concentration of 0.25 mg TP L(-1) from the three surface drainage events. Results indicate that avoiding overflow drainage after P input and extending the time between P application and drainage may reduce P losses from rice paddies.


Mechanism of antiulcer effect of Neem (Azadirachta indica) leaf extract: effect on H+-K+-ATPase, oxidative damage and apoptosis.
The mechanism of the antiulcer effect of Neem leaf aqueous extract to block gastric lesions in rat has been studied with emphasis on acid secretion, oxidative damage and apoptosis. The extract dose-dependently inhibits gastric lesions induced by restraint-cold stress, indomethacin and ethanol. In stress ulcer model, it is more effective than ranitidine but less effective than omeprazole. It also dose-dependently blocks pylorus ligation and mercaptomethylimidazole-induced acid secretion. In the pylorus-ligation model, it is less effective than omeprazole but as effective as ranitidine. It inhibits H+-K+-ATPase activity in vitro in concentration-dependent manner to inhibit acid secretion. Oxidative membrane damage by hydroxyl radical (*OH) as measured by lipid peroxidation in stress ulcer is significantly blocked by leaf extract. Stress-induced apoptotic DNA fragmentation is also protected. The extract also prevents *OH-mediated mucosal DNA damage in vitro by scavenging the *OH. Neem leaf extract, thus, offers antiulcer activity by blocking acid secretion through inhibition of H+-K+-ATPase and by preventing oxidative damage and apoptosis.


Determination of physicochemical properties of halofantrine.
The physicochemical properties of halofantrine hydrochloride (HF HCl)--a phenanthrene methanol antimalarial, were determined practically in this study since such experimental values are still unknown. The solubility in different solvents were determined and found to be 0.67%w/v in methanol (slightly soluble); 0.4%w/v in both n-octanol and acidified acetonitrile (slightly soluble); 0.09%w/v (very slightly soluble) and less than 0.002%w/v in warm water (50 degrees C) (practically insoluble). Halofantrine hydrochloride was found to be practically insoluble in water (at room temperature), n-hexane and phosphate buffer solution of pH 7.4. The partition coefficient between n-octanol and water gave a log p in the range of 3.20-3.26 (mean 3.20 +/- 0.04) and this was at variance with the log P of 8.5 estimated theoretically in literature. The value also confirms the lipophilicity of HF HCl. The ionisation constant (pKa) determined in partly aqueous solvent (40% methanol) ranged between 8.10 and 8.20 (mean 8.18 +/- 0.05) and confirms the monobasicity of halofantrine. This value also differed from the theoretical estimation of 9.6. The values obtained confirm the often unpredictable and erratic absorption of HF HCl, which bears direct relationship to the physicochemical properties and support the need for better formulations with improved drug delivery potentials.


Langevin dynamics of semiflexible polyelectrolytes: rod-toroid-globule-coil structures and counterion distribution.
We have investigated the nature of counterion condensation on uniformly charged semiflexible polyelectrolyte chains and the concomitant configurations by monitoring the role of chain stiffness, chain length, counterion valency, and the strength of electrostatic interaction. The counterion condensation is seen to follow the adsorption process and the effective polymer charge increases with chain stiffness. Size and shape, as calculated through the radius of gyration, effective persistence length, and hydrodynamic radius, are studied. Stable coil-like, globular, folded-chain, toroidal, and rodlike configurations are possible at suitable combinations of values of chain stiffness, chain length, electrostatic interaction strength, and the valency of counterion. For high strengths of electrostatic interactions, sufficiently stiff polyelectrolytes form toroids in the presence of multivalent counterions, whereas flexible polyelectrolytes form disordered globules. The kinetic features of the nucleation and growth of toroids are monitored. Several metastable structures are found to frustrate the formation of toroids. The generic pathway involves the nucleation of one primary loop somewhere along the chain contour, followed by a growth process where the rest of the chain is folded continuously on top of the primary loop. The dependence of the average radii of toroids on the chain length is found to be roughly linear, in disagreement with existing scaling arguments.


The molecular structure of the complex of Ascaris chymotrypsin/elastase inhibitor with porcine elastase.
The intestinal parasitic worm, Ascaris suum, produces a variety of protein inhibitors that defend the organism against the host's proteinases. Eight different proteins from Ascaris suum have been identified as inhibitors of serine proteinases, targeting chymotrypsin, elastase and trypsin. These inhibitors share 30-40% sequence identity with one another, but have virtually no sequence identity with members of any of the other families of serine proteinase inhibitors. The crystal structure of the complex of porcine pancreatic elastase with a chymotrypsin/elastase inhibitor from Ascaris suum (the C/E-1 inhibitor) has been solved to 2.4 A resolution by the molecular replacement method. The C/E-1 inhibitor exhibits a novel folding motif. There are only two small beta-sheets and two single-turn 3(10)-helices in this inhibitor. Unlike the majority of proteins, the C/E-1 inhibitor does not have a hydrophobic core. The presence and unique topography of the five disulfide bridges suggests that they play important roles in maintaining the tertiary structure of the inhibitor. In addition, the side chains of several charged residues from electrostatic and hydrogen-bonding cascades, which also probably compensate for the lack of extensive secondary structures and a hydrophobic core. The reactive-site loop of this inhibitor displays a conformation that is characteristic of most serine proteinase inhibitors. The structure of the C/E-1 inhibitor confirms that inhibitors from Ascaris suum belong to a novel family of proteinase inhibitors. It also provides conclusive evidence for the correct disulfide bridge connections. The C/E-1 inhibitor probably acts by a common inhibitory mechanism proposed for other substrate-like protein inhibitors of serine proteinases. The unusual molecular scaffolding presents a challenge to current folding algorithms. Proteins like the C/E-1 inhibitor may provide a valuable model system to study how the primary sequence of a protein dictates its three-dimensional structure.


Synergetic mechanisms of chiral symmetry breaking in prebiotic evolution.
It was shown on the Frank autocatalytic reaction-diffusion scheme that strong environmental fluctuations, conditioned by external noise (e.g. sunlight fluctuation) and external macroscopic flows (e.g. ebb and flow), typical for conditions on prebiotic earth, may have been beneficial for chiral symmetry breaking and formation and stabilization of biomolecular homochirality.


Analysis of estrogen receptor alpha signaling complex at the plasma membrane.
There is accumulating evidence that the estrogen receptor (ER) can transduce specific signals at the plasma membrane. We tried to clarify the biological function of ER as a signaling molecule by identifying proteins that interact with the membrane-localized ER. The activation function 1 and 2 (AF-1 and AF-2) domains of ERalpha with or without the membrane-targeting sequence were stably expressed in the breast cancer cell line, MCF-7. The level of tyrosine phosphorylation of AF-2 was significantly elevated by the membrane localization. By mass-spectrometry analysis, alpha- and beta-tubulins and heat shock protein 70 were identified as the AF-1-associated proteins. Of these, tubulins are associated only with membrane-targeted AF-1.


[Outlook for control of current zoonoses in swine--an issue on consumer health protection].
With the development of a uniform European strategy for the control of zoonoses the European Commission has placed the main emphasis on the protection of consumer health. This direction is clearly marked by the White Paper on Food Safety and the attached proposals for directives and regulations. The present article considers the peculiarities of the epidemiological situation of the agents Campylobacter spp. and Yersinia enterocolitica in pork production. The situation of zoonoses in Europe is used as an opportunity to present the distinctive characteristics of these agents, results of epidemiological studies available, and the risk to consumer health in light of the literature. For the approaching transfer of the responsibility for food safety to the primary producers, i.e. the farmers, the most interesting data concern the prevalence, distribution and risk factors. But as there is a strong need for clarification of further questions about the main ways of entry of these agents on farms and into the production chain before a successful preventive strategy can be developed on pig farms, these issues are considered in more detail here.


How bees distinguish black from white.
Bee eyes have photoreceptors for ultraviolet, green, and blue wavelengths that are excited by reflected white but not by black. With ultraviolet reflections excluded by the apparatus, bees can learn to distinguish between black, gray, and white, but theories of color vision are clearly of no help in explaining how they succeed. Human vision sidesteps the issue by constructing black and white in the brain. Bees have quite different and accessible mechanisms. As revealed by extensive tests of trained bees, bees learned two strong signals displayed on either target. The first input was the position and a measure of the green receptor modulation at the vertical edges of a black area, which included a measure of the angular width between the edges of black. They also learned the average position and total amount of blue reflected from white areas. These two inputs were sufficient to help decide which of two targets held the reward of sugar solution, but the bees cared nothing for the black or white as colors, or the direction of contrast at black/white edges. These findings provide a small step toward understanding, modeling, and implementing in silicon the anti-intuitive visual system of the honeybee, in feeding behavior.


The role of the health visitor in identifying and working with vulnerable families in relation to child protection: a review of the literature.
This paper presents an overview of the research surrounding the role of the health visitor in identifying and working with vulnerable families in relation to child protection. Only a limited number of empirical studies have been completed within the field of health visiting, so this review draws on most of the literature published over the last 15 years, which is mainly British in origin. No previous reviews have focused on this specific area of health visiting. Clearly with the recent increase in public and official recognition of child protection issues and the continuing debate of health visitor involvement within this area, this review takes a significant step forward in drawing together relevant research. The review focuses on research within three main areas. Firstly, the health visitor's role in working with vulnerable families in relation to child protection is explored. The clients' perceptions of this role are also explored. Secondly, the identification of vulnerable families by health visitors and non-health visitors is explored. Within this area a number of studies by non-health visitors investigating screening approaches to child abuse have been reviewed, because they play such a major role in the literature and appear to have influenced subsequent health visitor research. Thirdly, a review of health visitors' preventive work with vulnerable families is completed.


Cryptococcus neoformans as a Model for Radioimmunotherapy of Infections.
There is an obvious and urgent need for novel approaches to treat infectious diseases. The use of monoclonal antibodies in therapy of infectious diseases is now experiencing renewed interest. During the last 5 years radioimmunotherapy (RIT), a modality previously developed only for cancer treatment, has been successfully adapted for the treatment of experimental fungal, bacterial, and viral infections. As our model organism for studying the efficacy, mechanisms, potential toxicity, and radioresistance to RIT, as well as for comparison of RIT with the existing antimicrobial therapies we have chosen the encapsulated yeast Cryptococcus neoformans (CN). The success of RIT approach in laboratory studies provides encouragement for feasibility of therapeutically targeting microbes with labeled antibodies. In addition, the creation of "panantibodies" for RIT which would recognize antigens shared by the whole class of pathogens such as fungi, for example, would facilitate the introduction of RIT into the clinic.


Genetic Diversity of Potassium Ion Channel Proteins Encoded by Chloroviruses That Infect Chlorella heliozoae.
Chloroviruses are large, plaque-forming, dsDNA viruses that infect chlorella-like green algae that live in a symbiotic relationship with protists. Chloroviruses have genomes from 290 to 370 kb, and they encode as many as 400 proteins. One interesting feature of chloroviruses is that they encode a potassium ion (K+) channel protein named Kcv. The Kcv protein encoded by SAG chlorovirus ATCV-1 is one of the smallest known functional K+ channel proteins consisting of 82 amino acids. The KcvATCV-1 protein has similarities to the family of two transmembrane domain K+ channel proteins; it consists of two transmembrane α-helixes with a pore region in the middle, making it an ideal model for studying K+ channels. To assess their genetic diversity, kcv genes were sequenced from 103 geographically distinct SAG chlorovirus isolates. Of the 103 kcv genes, there were 42 unique DNA sequences that translated into 26 new Kcv channels. The new predicted Kcv proteins differed from KcvATCV-1 by 1 to 55 amino acids. The most conserved region of the Kcv protein was the filter, the turret and the pore helix were fairly well conserved, and the outer and the inner transmembrane domains of the protein were the most variable. Two of the new predicted channels were shown to be functional K+ channels.


Association of campus tobacco policies with secondhand smoke exposure, intention to smoke on campus, and attitudes about outdoor smoking restrictions.
College campus tobacco-free policies are an emerging trend. Between September 2013 and May 2014, we surveyed 1309 college students at 8 public 4-year institutions across California with a range of policies (smoke-free indoors only, designated outdoor smoking areas, smoke-free, and tobacco-free). Stronger policies were associated with fewer students reporting exposure to secondhand smoke or seeing someone smoke on campus. On tobacco-free college campuses, fewer students smoked and reported intention to smoke on campus. Strong majorities of students supported outdoor smoking restrictions across all policy types. Comprehensive tobacco-free policies are effective in reducing exposure to smoking and intention to smoke on campus.


Characteristics of and risk factors for severe neurological deficit in patients with pyogenic vertebral osteomyelitis: A case-control study.
Severe neurological deficit (SND) is a rare but major complication of pyogenic vertebral osteomyelitis (PVO). We aimed to determine the risk factors and the variables associated with clinical improvement for SND during PVO.This case-control study included patients without PVO-associated SND enrolled in a prospective randomized antibiotic duration study, and patients with PVO-associated SND managed in 8 French referral centers. Risk factors for SND were determined by logistic regression.Ninety-seven patients with PVO-associated SND cases, and 297 controls were included. Risk factors for SND were epidural abscess [adjusted odds ratio, aOR 8.9 (3.8-21)], cervical [aOR 8.2 (2.8-24)], and/or thoracic involvement [aOR 14.8 (5.6-39)], Staphylococcus aureus PVO [aOR 2.5 (1.1-5.3)], and C-reactive protein (CRP) >150 mg/L [aOR 4.1 (1.9-9)]. Among the 81 patients with PVO-associated SND who were evaluated at 3 months, 62% had a favorable outcome, defined as a modified Rankin score ≤ 3. No factor was found significantly associated with good outcome, whereas high Charlson index [adjusted Hazard Ratio (aHR) 0.3 (0.1-0.9)], low American Spinal Injury Association (ASIA) impairment scale at diagnosis [aHR 0.4 (0.2-0.9)], and thoracic spinal cord compression [aHR 0.2 (0.08-0.5)] were associated with poor outcome. Duration of antibiotic treatment was not associated with functional outcome.SND is more common in cervical, thoracic, and S. aureus PVO, in the presence of epidural abscess, and when CRP >150 mg/L. Although neurological deterioration occurs in 30% of patients in early follow-up, the functional outcome is quite favorable in most cases after 3 months. The precise impact of optimal surgery and/or corticosteroids therapy must be specified by further studies.


Tailoring graphene to achieve negative Poisson's ratio properties.
Graphene can be made auxetic through the introduction of vacancy defects. This results in the thinnest negative Poisson's ratio material at ambient conditions known so far, an effect achieved via a nanoscale de-wrinkling mechanism that mimics the behavior at the macroscale exhibited by a crumpled sheet of paper when stretched.


Are beta blockers new potential anticancer agents?
β-Blockers have been one of the most widely used and versatile drugs for the past half a century. A new potential for their use as anti-cancer drugs has emerged in the past few years. Various retrospective case control studies have been suggestive that use of β-blockers before the diagnosis of cancer could have preventive and protective effects against non-small cell lung carcinoma, melanoma, and breast, pancreatic and prostate cancers. Experimental and clinical observations are still inconclusive with some inconsistent findings. However, indications are pointing toward a positive role of some β-blockers against certain forms of cancers. This mini review is an effort to present the up to date published results of case-control studies and experimental findings.


Intracellular Localization during Blood-Brain Barrier Crossing Influences Extracellular Release and Uptake of Fluorescent Nanoprobes.
To improve the efficacy of nanoparticles (NPs) and boost their theragnostic potential for brain diseases, it is key to understand the mechanisms controlling blood-brain barrier (BBB) crossing. Here, the capability of 100 nm carboxylated polystyrene NPs, used as a nanoprobe model, to cross the human brain endothelial hCMEC/D3 cell layer, as well as to be consequently internalized by human brain tumor U87 cells, is investigated as a function of NPs' different intracellular localization. We compared NPs confined in the endo-lysosomal compartment, delivered to the cells through endocytosis, with free NPs in the cytoplasm, delivered by the gene gun method. The results indicate that the intracellular behavior of NPs changed as a function of their entrance mechanism. Moreover, by bypassing endo-lysosomal accumulation, free NPs were released from cells more efficiently than endocytosed NPs. Most importantly, once excreted by the endothelial cells, free NPs were released in the cell culture medium as aggregates smaller than endocytosed NPs and, consequently, they entered the human glioblastoma U87 cells more efficiently. These findings prove that intracellular localization influences NPs' long-term fate, improving their cellular release and consequent cellular uptake once in the brain parenchyma. This study represents a step forward in designing nanomaterials that are able to reach the brain effectively.


Analysis of mammalian viable cell biomass based on cellular ATP.
Analysis of cellular ATP as a means of measuring viable biomass loading was investigated in hybridoma cell culture. ATP analysis by the luciferin-luciferase assay was compared with trypan blue-stained hemocytometer counts. The cell-specific ATP content varied between 2 and 6 fmol per viable cell over a batch culture. ATP levels were highest during exponential growth, and decreased during the stationary and decline phases. Electronic counting and volume measurements were performed to assay the viable cell biomass. Cell sorting, using fluorescein diacetate, was used to separate viable and nonviable cells in cultures with between 35% and 90% viable cells. Viable cells contained over 2 orders of magnitude greater cell-specific ATP than nonviable cells. Cell-specific ATP correlated directly with the viable cell volume rather than viable cell numbers. Over the range of batch culture conditions, ATP analysis should provide a more accurate measurement of hybridoma viable biomass than hemocytometer counts.


Melanin and Glycera jaws: emerging dark side of a robust biocomposite structure.
Defining the design principles guiding the fabrication of superior biocomposite structures from an assemblage of ordinary molecules is a key goal of biomimetics. Considering their low degree of mineralization, Glycera jaws have been shown to be extraordinarily resistant to abrasion based on the metric hardness3/Young's modulus2. The jaws also exhibit an impressive chemical inertness withstanding boiling concentrated hydrochloric acid as well as boiling concentrated sodium hydroxide. A major organic component largely responsible for the chemical inertness of the jaws has been characterized using a spectrophotometric assay for melanin content, 13C solid state nuclear magnetic resonance, IR spectroscopy, and laser desorption ionization-time of flight mass spectrometry and is identified here as a melanin-like network. Although melanin is widely distributed as a pigment in tissues and other structural biomaterials, to our knowledge, Glycera jaws represent the first known integument to exploit melanin as a cohesive load- and shape-bearing material.


Evaluation of disaster preparedness for mass casualty incidents in private hospitals in Central Saudi Arabia.
To identify and describe the hospital disaster preparedness (HDP) in major private hospitals in Riyadh, Saudi Arabia. Methods: This is an observational cross-sectional survey study performed in Riyadh city, Saudi Arabia between December 2015 and April 2016. Thirteen major private hospitals in Riyadh with more than 100 beds capacity were included in this investigation. Results: The 13 hospitals had HDP plan and reported to have an HDP committee. In 12 (92.3%) hospitals, the HDP covered both internal and external disasters and HDP was available in every department of the hospital. There were agreements with other hospitals to accept patients during disasters in 9 facilities (69.2%) while 4 (30.8%) did not have such agreement. None of the hospitals conducted any unannounced exercises in previous year. Conclusion: Most of the weaknesses were apparent particularly in the education, training and monitoring of the hospital staff to the preparedness for disaster emergency occasion. Few hospitals had conducted an exercise with casualties, few had drilled evacuation of staff and patients in the last 12 months, and none had any unannounced exercise in the last year.


Preoperative Computed Tomography Angiography in Autologous Breast Reconstruction-Incidence and Impact of Incidentalomas.
Incidentalomas are lesions found coincidentally during examination, imaging, or surgical procedures. Preoperative computed tomography angiography (CTA) before abdominal flap harvest for breast reconstruction can lead to identification of incidentalomas leading to the need for further investigations. The aim of this study was to examine the prevalence of incidental findings on preoperative CTA and to determine their impact on management. A retrospective chart review was performed at a single tertiary institution. CTA reports were analyzed for the presence of incidental findings and details of follow-up were studied. Logistic regression was used to identify factors associated with incidental findings. One hundred eighteen patients with a mean age of 49 years were included in the study. The majority of patients underwent bilateral reconstruction (65%, n = 77) in the immediate setting (70%, n = 83). Fifty-six percentage had an incidental finding on CTA, with hepatic (20%), renal (14%), and osseous (11%) abnormalities being most common. Additional imaging including ultrasound, CT, and magnetic resonance imaging were recommended in 19 cases (16%). Additional consultations were sought for 3 patients before reconstruction (with suspicion of bone metastases, an intraabdominal mass, and suspicion of colonic malignancy, respectively). No significant surgical delay secondary to CT findings was noted. Incidentalomas following preoperative CTA of the abdomen/pelvis are common (56%). However, unlike previous reports, we did not observe a change in reconstructive plan following incidentaloma discovery. We recommend that all patients are counseled pre-CTA regarding the possibilities of incidentaloma detection and need for additional imaging.


Spatio-temporal coherence of dengue, chikungunya and Zika outbreaks in Merida, Mexico.
Response to Zika virus (ZIKV) invasion in Brazil lagged a year from its estimated February 2014 introduction, and was triggered by the occurrence of severe congenital malformations. Dengue (DENV) and chikungunya (CHIKV) invasions tend to show similar response lags. We analyzed geo-coded symptomatic case reports from the city of Merida, Mexico, with the goal of assessing the utility of historical DENV data to infer CHIKV and ZIKV introduction and propagation. About 42% of the 40,028 DENV cases reported during 2008-2015 clustered in 27% of the city, and these clustering areas were where the first CHIKV and ZIKV cases were reported in 2015 and 2016, respectively. Furthermore, the three viruses had significant agreement in their spatio-temporal distribution (Kendall W>0.63; p<0.01). Longitudinal DENV data generated patterns indicative of the resulting introduction and transmission patterns of CHIKV and ZIKV, leading to important insights for the surveillance and targeted control to emerging Aedes-borne viruses.


The broiler chicken as a signal of a human reconfigured biosphere.
Changing patterns of human resource use and food consumption have profoundly impacted the Earth's biosphere. Until now, no individual taxa have been suggested as distinct and characteristic new morphospecies representing this change. Here we show that the domestic broiler chicken is one such potential marker. Human-directed changes in breeding, diet and farming practices demonstrate at least a doubling in body size from the late medieval period to the present in domesticated chickens, and an up to fivefold increase in body mass since the mid-twentieth century. Moreover, the skeletal morphology, pathology, bone geochemistry and genetics of modern broilers are demonstrably different to those of their ancestors. Physical and numerical changes to chickens in the second half of the twentieth century, i.e. during the putative Anthropocene Epoch, have been the most dramatic, with large increases in individual bird growth rate and population sizes. Broiler chickens, now unable to survive without human intervention, have a combined mass exceeding that of all other birds on Earth; this novel morphotype symbolizes the unprecedented human reconfiguration of the Earth's biosphere.


Dithiafulvenyl-Extended N-Heterotriangulenes and Their Interaction with C60 : Cooperative Fluorescence.
We describe the synthesis as well as the electronic and photophysical characterization of novel N-heterotriangulene derivatives decorated with methoxycarbonyl- and methyl-sulfanyl-substituted dithiafulvenyl moieties. The association of these electron-rich compounds with fullerene C60 as electron acceptor was investigated by means of photophysical, voltammetric, and mass spectrometric methods and rationalized by DFT calculations. Importantly, light-induced interactions between the dithiafulvene-substituted N-heterotriangulene bearing methoxycarbonyl substituents with C60 leads to cooperative fluorescence. Quantitative Job plot analyses by means of fluorescence spectroscopy and voltammetry confirm a 1:1 association with binding constants in the order of 104 m-1 . Supportive results for the supramolecular assembly of both N-heterotriangulenes with C60 were obtained by ESI mass spectrometric investigations in the gas phase.


Do e-cigarettes have the potential to compete with conventional cigarettes?: a survey of conventional cigarette smokers' experiences with e-cigarettes.
Electronic cigarettes (ECs) are becoming increasingly popular globally. If they were to replace conventional cigarettes, it could have a substantial impact on public health. To evaluate EC's potential for competing with conventional cigarettes as a consumer product, we report the first data, to our knowledge, on the proportion of smokers who try ECs and become regular users. A total of 2,012 people seen smoking or buying cigarettes in the Czech Republic were approached to answer questions about smoking, with no mention made of ECs to avoid the common bias in surveys of EC users. During the interview, the volunteers' experience with ECs was then discussed. A total of 1,738 smokers (86%) participated. One-half reported trying ECs at least once. Among those who tried ECs, 18.3% (95% CI, 0.15.7%-20.9%) reported using them regularly, and 14% (95% CI, 11.6%-16.2%) used them daily. On average, regular users used ECs daily for 7.1 months. The most common reason for using ECs was to reduce consumption of conventional cigarettes; 60% of regular EC users reported that ECs helped them to achieve this. Being older and having a more favorable initial experience with ECs explained 19% of the variance in progressing to regular EC use. Almost one-fifth of smokers who try ECs once go on to become regular users. ECs may develop into a genuine competitor to conventional cigarettes. Government agencies preparing to regulate ECs need to ensure that such moves do not create a market monopoly for conventional cigarettes.


Mesenchymal stem cell-derived exosomes: a possible therapeutic strategy for repairing heart injuries.
Mesenchymal stem cells (MSCs) are one of the most potent therapeutic strategies for repairing cardiac injury. It has been shown in the latest studies that MSCs cannot survive in the heart for a long time. Consequently, the exosomes secreted by MSCs may dominate the repair of heart injury and promote the restoration of cardiac cells, vascular proliferation, immune regulation, etc. Based on the current research, the progress of the acting mechanism, application prospects and challenges of exosomes, including non-coding RNA, in repairing cardiac injuries are summarised in this article.


Organ-specific and age-dependent expression of insulin-like growth factor-I (IGF-I) mRNA variants: IGF-IA and IB mRNAs in the mouse.
Insulin-like growth factor-I (IGF-I) gene generates several IGF-I mRNA variants by alternative splicing. Two promoters are present in mouse IGF-I gene. Each promoter encodes two IGF-I mRNA variants (IGF-IA and IGF-IB mRNAs). Variants differ by the presence (IGF-IB) or absence (IGF-IA) of a 52-bp insert in the E domain-coding region. Functional differences among IGF-I mRNAs, and regulatory mechanisms for alternative splicing of IGF-I mRNA are not yet known. We analyzed the expression of mouse IGF-IA and IGF-IB mRNAs using SYBR Green real-time RT-PCR. In the liver, IGF-I mRNA expression increased from 10 days of age to 45 days. In the uterus and ovary, IGF-I mRNA expression increased from 21 days of age, and then decreased at 45 days. In the kidney, IGF-I mRNA expression decreased from 10 days of age. IGF-IA mRNA levels were higher than IGF-IB mRNA levels in all organs examined. Estradiol-17beta (E2) treatment in ovariectomized mice increased uterine IGF-IA and IGF-IB mRNA levels from 3 hr after injection, and highest levels for both mRNAs were detected at 6 hr, and relative increase was greater for IGF-IB mRNA than for IGF-IA mRNA. These results suggest that expression of IGF-I mRNA variants is regulated in organ-specific and age-dependent manners, and estrogen is involved in the change of IGF-I mRNA variant expression.


From dentistry students' points of view: do anatomy classes we took actually boost our learning during clinic?
The aim of medical education is to teach the essence of practical skills alongside with the theoretical knowledge. Teaching anatomy, as the center of medical education, should be leading to use this knowledge as a skill during clinical period. According to the rising numbers of dentistry faculties' experiences, inappropriate education results in misguidance during clinic. Thus, this study was conducted to find about the pre-clinical and clinical dentistry students' points of view on the helpfulness of anatomy classes in achieving clinical goals. Present descriptive cross-sectional study evaluated Guilan University of Medical Sciences' pre-clinical and clinical dentistry students' opinions on the effectiveness of anatomy classes during their clinical period in 2017. The sampling method used here was census via questionnaire and scoring was according to Likert scaling system. Analyses showed that anatomy of the nervous system was the most assistive course, which helped dentistry students during their clinical period (P<0.001). The least scored course was visceral organs and that means they did not use most of their learnings from classes with this topic (P<0.001). They also stated that other important factors such as using cadavers and moulages in practical sessions, teaching clinical skills theoretically before practical sessions and performing group activities are crucial for them to recall important details of the relevant courses during clinical period. Results of this study suggests that alongside with the various topics of anatomy courses, other factors like professors' characteristics and their teaching methods are also of important factors helping the dentistry students throughout clinic.


Value of small patches in the conservation of plant-species diversity in highly fragmented rainforest.
We evaluated the importance of small (<5 ha) forest patches for the conservation of regional plant diversity in the tropical rainforest of Los Tuxtlas, Mexico. We analyzed the density of plant species (number of species per 0.1 ha) in 45 forest patches of different sizes (1-700 ha) in 3 landscapes with different deforestation levels (4, 11, and 24% forest cover). Most of the 364 species sampled (360 species, 99%) were native to the region, and only 4 (1%) were human-introduced species. Species density in the smallest patches was high and variable; the highest (84 species) and lowest (23 species) number of species were recorded in patches of up to 1.8 ha. Despite the small size of these patches, they contained diverse communities of native plants, including endangered and economically important species. The relationship between species density and area was significantly different among the landscapes, with a significant positive slope only in the landscape with the highest deforestation level. This indicates that species density in a patch of a given size may vary among landscapes that have different deforestation levels. Therefore, the conservation value of a patch depends on the total forest cover remaining in the landscape. Our findings revealed, however, that a great portion of regional plant diversity was located in very small forest patches (<5 ha), most of the species were restricted to only a few patches (41% of the species sampled were distributed in only 1-2 patches, and almost 70% were distributed in 5 patches) and each landscape conserved a unique plant assemblage. The conservation and restoration of small patches is therefore necessary to effectively preserve the plant diversity of this strongly deforested and unique Neotropical region.


Expression and regulation of nonsteroidal anti-inflammatory drug-activated gene (NAG-1) in human and mouse tissue.
Nonsteroidal anti-inflammatory drugs (NSAIDs) induce NSAID-activated gene 1 (NAG-1), which has proapoptotic and antitumorigenic activities. However, NAG-1 expression and its relationship with apoptosis in human and mouse intestinal tract have not been determined. NAG-1 expression in human and mouse tissue was determined by immunohistochemistry, and apoptosis was estimated by in situ apoptosis detection. Apoptosis in NAG-1 overexpressing HCT-116 cells was examined with flow cytometry after cell sorting by green fluorescence protein. NAG-1 regulation in mouse cells was examined by Northern blot analysis, comparing sulindac-treated and nontreated mice. Apoptosis was higher in NAG-1 overexpressing cells compared with controls. Human NAG-1 protein was localized to the colonic surface epithelium where cells undergo apoptosis, and higher expression was observed in the normal surface epithelium than in most of the tumors. This localization and lower expression in tumors was similar to that in the Min mouse, in which NSAIDs were also shown to regulate the expression of NAG-1 in mouse cells. Sulindac treatment of mice increased the NAG-1 expression in the colon and liver. Based on these results, we propose that NAG-1 acts as a mediator of apoptosis in intestinal cells and may contribute to cancer chemoprevention by NSAIDs.


Chronic extradural haematoma with delayed expansion.
A 35-year-old man became symptomatic 26 months after a head injury. CT showed an occipital-suboccipital chronic extradural haematoma (EDH). A surrounding membrane, with neovascularisation, was evident, both, on CT and at surgery. This unusually long interval between trauma and onset of symptoms suggests that delayed expansion of a chronic EDH should be kept in mind if planning conservative management. An EDH can be considered 'cured' only after disappearance of the membrane and haematoma on CT.


The immune system as a supersystem.
I coined a term "supersystem" to designate highly integrated life systems such as the immune system, nervous system, and embryogenesis. While the mechanistic system is defined as a set of diverse elements so connected and related as to form an organic whole for a particular purpose, the "supersystem" engenders its own elements from a single progenitor. The diverse elements thus generated form relationship by mutual adaptation and coadaptation, and thus they create a dynamic self-regulating system through self-organization. It is a closed self-satisfied system, yet open to the environment, receiving outside signals to transduce them into internal messages for self-regulation and expansion. Unlike a mechanistic system, the "supersystem" has no defined purpose and determines its own fate by referring to its self-established behavioral pattern. Both the immune and nervous systems develop and function as a typical "supersystem." The prototype of the supersystem can be seen in embryogenesis and evolution. The concept of the supersystem can also be applied to the development of language, or a city, or other cultural phenomena that human beings have created as a result of their vital activities.


[Construction and expression of the major outer membrane protein PI of Neisseria gonorrhoeae in Escherichia coli].
To construct Neisseria gonorrhoeae major outer membrane protein PI gene recombinants for expression of the target protein in E. coli. Four clinic isolates of Neisseria gonorrhoeae were collected, and then the genome DNA of these strains was extracted. The gene encoding for PI of Neisseria gonorrhoeae was amplified by PCR, inserted into the cloning vector pBS-T; the recombinant plasmids pBS-T-PI-NG were constructed and sequence analysis was performed. Then PI gene fragments were inserted into expression vector pET30b to form pET30b-PI-NG recombinants. The PI protein expression was induced by adding IPTG in the inocula. The expressed proteins were analyzed by SDS-PAGE. The pET30b-PI-NG expression recombinants for four clinic isolates of Neisseria gonorrhoeae were constructed successfully; three of the four expression recombinants were expressed successfully. The expressed PI protein will be applied in the further research for PI antigenicity and immunological activity. This will be very helpful for the further construction of preventive vaccines directed against Neisseria gonorrhoeae infection.


Covictimization and inner city youth: a review.
Covictimization represents a real and present danger to inner city youth. This paper reviews the scope of this problem and a potential emergency mental health response.


Metal-based Complexes as Potential Anti-cancer Agents.
Metal based therapy is no new in biomedical research. In early days, the biggest limitation was the inequality among therapeutical and toxicological dosages. Ever since, Barnett Rosenberg discovered cisplatin, a new era has begun to treat cancer with metal complexes. Platinum complexes such as oxaliplatin, cisplatin, and carboplatin, seem to be the foundation of metal/s-based components to challenge malignancies. With advancement in the biomolemoecular mechanism, researchers have started developing non-classical platinum-based complexes, where a different mechanistic approach of the complexes is observed towards the biomolecular target. Till date, larger numbers of metal/s-based complexes were synthesized by overhauling the present structures chemically by substituting the ligand or preparing the whole novel component with improved cytotoxic and safety profiles. Howsoever, due to elevated accentuation upon the therapeutic importance of metal/s-based components, a couple of those agents are at present in clinical trials and several other are in anticipating regulatory endorsement to enter the trial. This literature highlights the detailed heterometallic multinuclear components, primarily focusing on platinum, ruthenium, gold and remarks on possible stability, synergism, mechanistic studies and structure activity relationships.


Smell loss as initial symptom of olfactory groove meningioma.
Approximately 20% of the general population suffer from olfactory dysfunction (OD). Until today, olfactory function (OF) receives less attention than other human senses despite its significance for quality of life. The main causes of OD are upper respiratory tract infections, traumatic brain injuries and sinonasal diseases. Here, we report the case of a 28-year-old woman, who started to suffer from OD during pregnancy. Smell loss was attributed to pregnancy-induced rhinitis and initiated no further examinations. Nevertheless, OD persisted post partum and undulating headache occurred 1 year later. Only after visual impairment and one more year passing by, diagnosis of olfactory groove meningioma was made using MRI. With this case report, we want to highlight the importance of the symptom of smell loss. Patients reporting OD should undergo thorough anamnesis, endoscopy of the nasal cavity, psychophysical smell testing and radiographic imaging in unclear cases to determine diagnosis.


Uncoupled redox stress: how a temporal misalignment of redox-regulated processes and circadian rhythmicity exacerbates the stressed state.
Diurnal and seasonal rhythmicity, entrained by environmental and nutritional cues, is a vital part of all life on Earth operating at every level of organization; from individual cells, to multicellular organisms, whole ecosystems and societies. Redox processes are intrinsic to physiological function and circadian regulation, but how they are integrated with other regulatory processes at the whole-body level is poorly understood. Circadian misalignment triggered by a major stressor (e.g. viral infection with SARS-CoV-2) or recurring stressors of lesser magnitude such as shift work elicit a complex stress response that leads to desynchronization of metabolic processes. This in turn challenges the system's ability to achieve redox balance due to alterations in metabolic fluxes (redox rewiring). We infer that the emerging 'alternative redox states' do not always revert readily to their evolved natural states; 'Long COVID' and other complex disorders of unknown aetiology are the clinical manifestations of such rearrangements. To better support and successfully manage bodily resilience to major stress and other redox challenges needs a clear perspective on the pattern of the hysteretic response for the interaction between the redox system and the circadian clock. Characterization of this system requires repeated (ideally continuous) recording of relevant clinical measures of the stress responses and whole-body redox state (temporal redox phenotyping). The human/animal body is a complex 'system of systems' with multi-level buffering capabilities, and it requires consideration of the wider dynamic context to identify a limited number of stress-markers suitable for routine clinical decision making. Systematically mapping the patterns and dynamics of redox biomarkers along the stressor/disease trajectory will provide an operational model of whole-body redox regulation/balance that can serve as basis for the identification of effective interventions which promote health by enhancing resilience.


Vaccine engineering improved by hybrid technology.
The term 'vaccination' describes the induction of protective immune responses against infectious diseases, but is also used to define antigen-specific forms of immunotherapy for allergy, cancer and autoimmunity. Successful vaccination requires either immune modulation or the induction of robust specific immunity to several disease-causing antigens. However, natural antigen sources may contain greatly varying amounts of these antigens and some of them may exhibit low immunogenicity. An approach for overcoming the latter problems has been developed for allergy vaccines recently. This approach is based on the genetic engineering of hybrid molecules, consisting of several major disease-eliciting antigens/epitopes. Such hybrid molecules can be built to include the most relevant epitopes of complex antigen sources. Moreover, fusion of different antigens in the form of hybrid molecules strongly increases their immunogenicity. The hybrid approach can also be used for the generation of mosaic antigens with altered immunological properties, which consist of re-shuffled antigen pieces. We exemplify the use of hybrid technology for the generation of new allergy vaccines and discuss its potential applicability for the development of vaccines for infectious diseases, cancer and autoimmunity.


Dietary cadmium and benzo(a)pyrene increased intestinal metallothionein expression in the fish Fundulus heteroclitus.
Fish were individually fed food pellets containing cadmium, benzo(a)pyrene, or a combination of the two, then analyzed for metallothionein mRNA expression in the intestine, liver, and gill using real-time RT-qPCR. An initial experiment using only cadmium showed that ingestion of pellets varied in individual fish, and estimates of cadmium dose from the numbers of ingested pellets indicated considerable individual variability in cadmium dose. Induction of intestinal metallothionein mRNA was apparent, however, and a linear dose-response relationship was observed for metallothionein expression and cadmium dose in the intestine, but not the other organs, which showed no induction. In a second experiment, the entire daily cadmium dose was provided in a single contaminated pellet that was consumed by all treated fish, effectively eliminating the effect of variable ingestion rates on dose, and the interaction between cadmium and benzo(a)pyrene was also investigated. The intestine was again the primary organ for metallothionein induction by cadmium. When benzo(a)pyrene was administered together with cadmium, induction of metallothionein was potentiated by the presence of benzo(a)pyrene, with the main effect seen in the intestine, where already high levels of induction by cadmium alone increased by 1.74-fold when benzo(a)pyrene was present.


The synthesis of unconventional stoichiometric compounds in the K-Br system at high pressures.
Recently, the search for and synthesis of unconventional stoichiometric compounds have become one of the most active areas of high pressure research. Here, we report the synthesis of two new stoichiometric compounds, namely KBr3 and KBr5, at high pressures in the K-Br system. Until now, KBr was the only known compound in this system. Two independent experimental techniques, namely Raman spectroscopy and X-ray diffraction measurements, were employed to detect and confirm the formation of the new compounds. A room temperature chemical reaction between KBr and Br2 resulted in the formation of orthorhombic KBr3 at ∼2.0 GPa. Further compression led to the formation of monoclinic KBr5 at ∼6.0 GPa. This was accompanied by an anomalously large pressure (>2 GPa) increase inside the sample chamber and it remained stable up to the highest pressure, 24 GPa, of our study. Upon decompression, KBr5 remained stable down to 5.0 GPa. High-pressure (14-20 GPa) and high-temperature (>1500 K) laser heating experiments showed the decomposition of KBr5 into KBr3 (trigonal) and Br2 with a large volume reduction. First-principles structural searches were carried out to solve the composition and related crystal structures. The proposed structures give good description of the experimental Raman spectra and X-ray diffraction data. The electronic structure calculations reveal semiconducting behaviour for these compounds.


Epidemiology and etiology of chemical ocular injury: A brief review.
Chemical ocular injury is one of the common ophthalmologic emergencies that can cause vision loss and serious complications. Despite all protective measures, it continues to be a serious public health problem, especially in young male patients. Although it is known that injuries occur most frequently in the workplace and in young male patients, there is a variable frequency and distribution in different regions around the world. In addition, with the coronavirus disease 2019 pandemic, there are changing trends in ocular chemical injuries. This review aims to specify an update on the epidemiological and etiological features of ocular chemical injuries.


"Adding pizzazz". A presentation skills workshop for healthcare practitioners.
Healthcare practitioners are often called upon to share their expertise with colleagues. Frequently, expert practitioners are asked to make presentations at patient support groups, professional rounds, workshops, meetings, and conferences. Often these expert practitioners have not had the opportunity to develop strong presentation skills. Consequently, many are reluctant to give presentations. When they do present, they often have difficulty communicating their ideas effectively. This article describes the creation of a presentation skills program for healthcare practitioners. Essential program content is identified as well as measures taken to make this an effective, economical, and popular training program.


The value of serum uric acid in predicting adverse pregnancy outcomes of women with hypertensive disorders of pregnancy.
This study aims to investigate the clinical value of uric acid in predicting adverse pregnancy outcomes (APOs) of women with hypertensive disorders of pregnancy. A total of 180 pregnant women with HDP from September 2015 to January 2017 were selected for this study. These subjects were classified into two groups, according to serum uric acid level: high UA group (n = 137) and normal UA group (n = 43). In addition, 180 healthy pregnant women were selected and assigned as the control group (n = 180). The monitored biochemical indices and APOs in these three groups were analyzed. Furthermore, non-conditional logistic regression analysis was performed to determine influencing factors of APOs in women with HDP and hyperuricemia. The non-conditional multi-factor logistic regression analysis revealed that HUA (SUA > 357 umol/L) is the risk factor of APOs in women with HDP (OR = 1.258, P < 0.05). Women with HDP and HUA are often accompanied with a variety of abnormal biochemical indicators, and is correlated with the severity of the disease and APOs.


Identification of Haemophilus haemolyticus in clinical samples and characterization of their mechanisms of antimicrobial resistance.
The objectives of this study were to establish the frequency of Haemophilus haemolyticus in clinical samples, to determine the antimicrobial resistance rate and to identify the mechanisms of resistance to β-lactams and quinolones. An updated database was used to differentiate between MALDI-TOF MS results for Haemophilus influenzae and H. haemolyticus. Antimicrobial susceptibility was studied by microdilution, following EUCAST criteria. The β-lactamase types were identified by PCR analysis of isolates that tested positive for nitrocefin hydrolysis. Mutations in the ftsI gene were identified in isolates with ampicillin MICs ≥0.25 mg/L. Mutations in the quinolone resistance-determining region (QRDR) were identified in isolates with ciprofloxacin MICs ≥0.5 mg/L. Overall, we identified 69 H. haemolyticus isolates from 1706 clinical isolates of Haemophilus spp. from respiratory, genital, invasive, and other infection sources. The frequency of H. haemolyticus was low in respiratory samples compared with that of H. influenzae, but in genital-related samples, the frequency was similar to that of H. influenzae. We found low antimicrobial resistance rates among H. haemolyticus isolates, with 8.7% for ampicillin, 8.7% for co-trimoxazole, 7.2% for tetracycline and 4.3% for ciprofloxacin. Mutations in the ftsI gene classified the isolates into four groups, including the newly described Group Hhae IV, which presents mutations in the ftsI gene not identified in H. influenzae and H. haemolyticus type strains. Three ciprofloxacin-resistant H. haemolyticus isolates with mutations affecting GyrA and ParC were identified. The frequency of H. haemolyticus was low, especially in respiratory samples, where H. influenzae is the main pathogen of this genus. Although antimicrobial resistance rates were low, three ciprofloxacin-resistant H. haemolyticus clinical isolates have been identified for the first time.