Impairments of astrocytes are involved in the d-galactose-induced brain aging.
Astrocyte dysfunction is implicated in course of various age-related neurodegenerative diseases. Chronic injection of d-galactose can cause a progressive deterioration in learning and memory capacity and serve as an animal model of aging. To investigate the involvement of astrocytes in this model, oxidative stress biomarkers, biochemical and pathological changes of astrocytes were examined in the hippocampus of the rats with six weeks of d-galactose injection. d-galactose-injected rats displayed impaired antioxidant systems, an increase in nitric oxide levels, and a decrease in reduced glutathione levels. Consistently, western blotting and immunostaining of glial fibrillary acidic protein showed extensive activation of astrocytes. Double-immunofluorescent staining further showed activated astrocytes highly expressed inducible nitric oxide synthase. Electron microscopy demonstrated the degeneration of astrocytes, especially in the aggregated area of synapse and brain microvessels. These findings indicate that impairments of astrocytes are involved in oxidative stress-induced brain aging by chronic injection of d-galactose.


Identification of Need for Ultrasound Enhancing Agent Study (the IN-USE Study).
Ultrasound enhancing agents (UEAs) are routinely used to improve transthoracic echocardiographic (TTE) image quality, yet anticipation of UEA need is a barrier to their use. Structured report data from 171,509 consecutive TTE studies in 97,515 patients who underwent TTE imaging from January 26, 2000, to September 20, 2018, were analyzed. Trends in UEA use and suboptimal image quality were examined. Among outpatients (92,291 TTE examinations, n = 56,479), the data set was randomly split into a 75% derivation sample and a 25% validation sample. Logistic regression was used to model the composite of either UEA receipt or suboptimal image quality (two or more nonvisualized segments) using only variables available at the start of the TTE examination. Model performance was tested in the validation sample. A total of 4,444 TTE examinations (2.6%) in 3,827 patients (3.9%) involved UEAs, and 28,468 TTE examinations (16.6%) in 21,994 patients (22.5%) were suboptimal. UEA use increased over the observation period. Among TTE studies with suboptimal image quality, UEA use was lower in women (P < .0001). Among outpatients referred for TTE imaging, older age, greater weight, and higher heart rate best predicted UEA use or suboptimal image quality. Model performance in the validation sample was excellent (C statistic = 0.74 [95% CI, 0.73-0.75]; calibration slope = 1.11 [95% CI, 1.06-1.15]). In this large, single-center, retrospective study, UEA use remained substantially below rates of suboptimal image quality, despite increases over time. Among outpatients, a simple prediction rule using three routinely collected variables available before TTE image acquisition predicted potential benefit from UEAs with high accuracy. If confirmed in other cohorts, this rule may be used to identify patients who may benefit from intravenous placement for UEA administration before TTE image acquisition, thus potentially improving work-flow efficiency.


Photoaffinity labeling of beef liver monoamine oxidase-B by 4-fluoro-3-nitrophenyl azide.
4-Fluoro-3-nitrophenyl azide (FNPA) competitively inhibited beef liver monoamine oxidase-B (MAO-B) in the dark (Ki = 2.8 microM). Upon irradiation in the presence of FNPA, a concentration-dependent photoinactivation of MAO-B was observed. The kinetic analysis showed that the photoinactivation of MAO-B resulted in a decrease in Vmax but no change in Km. This result suggests that an irreversible linkage may be formed between the enzyme and the photolyzed FNPA. When [3H]FNPA was photoirradiated with the purified MAO-B, a single radioactive band associated with MAO-B was observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The photo-dependent incorporation could be protected by phenylethylamine, the substrate for MAO-B, in a concentration-dependent manner. Complete tryptic-chymotryptic digestion of [3H]FNPA-labeled MAO-B resulted in three radioactive peaks on Sephadex G-25 column chromatography. With the same digestion and separation procedures, only one major radioactive peak was observed for the [3H]pargyline-labeled MAO-B, and its elution volume was different from that of [3H]FNPA-labeled peptides. These results suggest that, upon photolysis, FNPA may incorporate into a region in the active site of MAO-B which may be different from the pargyline binding site--the FAD prosthetic group of the enzyme.


Experimental research on the performance of a very-small-aperture laser.
Very-small-aperture lasers (VSALs) with different aperture shapes are fabricated. Their far-field and near-field performance is analyzed experimentally. The far-field performance, including the threshold current, the slope efficiency, the lasing ability and the linear frequency modulation property, is found to be influenced by the front facet reflectivity. A new factor is tentatively proposed to analyze the lasing abilities of VSALs with different aperture shapes. This factor can diminish the discrepancies among the same type laser diodes. The near-field performance focusses on the confinement effect of the VSAL aperture. A near-field scanning optical microscopy is used to measure the near-field intensity distribution from a VSAL. The experimental results indicate that the near-field performance is affected by the aperture shape. A 100-nm C-aperture is proved to be superior to a 100 x 300 nm(2) rectangular aperture on both power throughput and peak intensity. These two apertures are fabricated on the same VSAL facet for the fairness of comparison. An optical spot beyond the diffraction limit is also obtained by fabricating a 70-nm C-aperture on a VSAL facet.


Intraventricular hemorrhage in the term infant.
Intraventricular hemorrhage (IVH) in the term infant is an uncommon and unexpected diagnosis. This article examines the frequency of IVH in the term newborn; the pathogenesis behind IVH; the presentation according to the location, extent, and cause of the hemorrhage; the diagnosis, associated complications, management, and outcomes of infants with IVH; and nursing responsibilities. A case study is offered of a term infant who presented with seizures after a normal labor and delivery, was found to have bilateral Grade III hemorrhages, and proceeded to develop posthemorrhagic hydrocephalus. Her management and outcome to date are discussed.


Heterotopic ossification of the long head of the triceps after reverse total shoulder arthroplasty.
Heterotopic ossification (HO) around shoulder arthroplasty is a frequent finding with unclear clinical relevance. This study evaluated the incidence, relevance, and predisposing factors of HO in the long head of the triceps tendon after reverse shoulder arthroplasty. Retrospective chart review was conducted to identify patients who had a reverse shoulder arthroplasty performed between 2008 and 2012. Patient demographics, implant types, and diagnoses were noted. Three fellowship-trained shoulder/elbow surgeons independently evaluated postoperative Grashey radiographs using a novel classification system. Within a 164-patient cohort, the overall HO rate in the long head of the triceps tendon was 61.6%; 23.2% of osteophytes were considered impinging, 14.6% had notching, 14.0% were free-floating, and 3.0% appeared ankylosed. Although not statistically significant, revision surgery had a higher rate of HO (68.3%) compared with primary surgery (59.4%). There was no difference in HO rates between diagnoses or implant types. Male and female HO rates were 74.0% and 56.1%, respectively (P = .0304). Between patients with and without HO, forward elevation was 121° compared with 133° (P = .0087) and external rotation was 19° compared with 25° (P = .0266); however, HO size did not significantly affect motion. Using our novel classification scheme, HO was a common finding in this series. Men had a higher rate of HO formation, and HO formation was associated with worse postoperative motion. Further study is needed to fully characterize the clinical implications of HO involving the long head of the triceps tendon and to explore potential preventive measures.


A newly discovered member of the fatty acid desaturase gene family: a non-coding, antisense RNA gene to delta5-desaturase.
The rate limiting steps in the conversion of 18-carbon unsaturated fatty acids to 20- and 22-carbon products are catalyzed by two desaturase enzymes (Delta5-desaturase and Delta6-desaturase) found within a lipid desaturase gene cluster. Careful examination of this cluster revealed the existence of a conventionally spliced (human) and an intronless (mouse and rat) non-coding RNA gene, reverse Delta5-desaturase, which is transcribed from the opposite strand of the Delta5-desaturase gene. The 654 bp human reverse Delta5-desaturase transcript contains 269 nucleotides that are complementary to exon 1 and intron 1 of the Delta5-desaturase transcript, and the 3'-end of this sequence contains a 143 nucleotide stretch that is 100% complementary to the 5'-end of the Delta5-desaturase. The rat and mouse transcripts are 1355 and 690 bp long and complementary to a portion of the first intron and the entire first exon of their respective Delta5-desaturases. All reverse Delta5-desaturase transcripts contain several stop codons in all frames suggesting that they do not encode a peptide. Reverse Delta5-desaturase RNA was detected in all rat tissues where Delta5-desaturase is expressed, and the transition between fasting and refeeding produced a significant increase in reverse Delta5-desaturase RNA relative to Delta5-desaturase mRNA. Transient expression of reverse Delta5-desaturase in CHO cells stably transformed with Delta5-desaturase produced a modest decrease in Delta5-desaturase mRNA (30%), but lowered Delta5-desaturase enzymatic activity by >70%. More importantly, a diet enriched in fish oil produced a reciprocal increase in reverse Delta5-desaturase mRNA and decrease in Delta5-desaturase mRNA that was accompanied by a 5-6-fold decrease in Delta5-desaturase enzyme activity. These findings support a significant role for reverse Delta5-desaturase as a natural antisense regulator of Delta5-desaturase.


Voltammetric studies on the electrochemical behaviour of membrane-entrapped hemes.
The electrochemical behaviour of Fe(III)-protoporphyrin IX entrapped into a cellulose triacetate membrane has been investigated by cyclic voltammetry. The physical entrapment into a solid matrix does not modify the redox properties of the entrapped hemes, which also act as efficient promoters in the electrochemistry of cytochrome c. Such a system represents a promising example of a simple 'solid-state' promoter, and stimulates further investigations in order to obtain more complex systems that may be of significance for basic and applied bioelectrochemistry.


Adsorption of TCDD with 1-butyl-3-methylimidazolium dicyanamide ionic liquid: a combined molecular dynamics simulation and quantum chemistry study.
The effective abatement of flue gas emissions, especially polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), is one of the challenging issues in the field of environmental science currently. Imidazolium-based dicyanamide ionic liquids (ILs) were proposed to have potential in controlling the emissions of PCDD/Fs. However, the relevant mechanism at the molecular level still remains unclear. To address this subject, we here present a combined molecular dynamics (MD) simulation and quantum chemical (QM) study on the adsorption of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener among PCDD/F family, by 1-butyl-3-methylimidazolium dicyanamide IL, a representative imidazolium dicyanoamide ILs, which were demonstrated to possess high capture capability for PCDD/Fs. The MD simulation results show that TCDD molecules can be effectively adsorbed on the IL surface to form a dense layer, but cannot enter the interior of the IL. The results of QM calculations show that the adsorption of TCDDs on the IL surface occurs via intra-molecular hydrogen bond interactions. The calculated interaction energy of the anion with TCDD molecule is two times more than that of the cation, implying that the IL anion dominates the interaction with TCDD molecules, while the cation plays a secondary role. Based on the calculated results, we propose that imidazolium dicyanamide IL films/membranes may be better materials than the corresponding bulk for capturing TCDD. The present theoretical results may be helpful to designing the functional ILs which effectively capture and concentrate PCDD/F compounds.


A genome-wide survey suggests an osmoprotective role for vacuolar Ca2+ release in cell wall-compromised yeast.
In yeast, osmotic upshock causes a release of vacuolar Ca(2+) through the mechanosensitive transient receptor potential channel, Yvc1. We screened the collection of 4810 yeast gene deletants twice for alterations in this response in an attempt to find elements that regulate the amount of vacuolar Ca(2+) or the Yvc1 channel. Severe overresponders and underresponders to upshock were further scrutinized for their calcium content with (45)Ca and their Yvc1 electrophysiological activities under patch-clamp. The severe underresponders have lower calcium content but no change in Yvc1 activity. The strong overresponders, most of which are deleted of genes involved in cell wall metabolism, have higher calcium content. Wall mutations are known to up-regulate Ca(2+)-calcineurin-dependent genes. It appears that stress on the cell wall induces Ca(2+) accumulation, adaptively anticipating the need in defense or repair against future stress, including osmotic stress.


Comprehension of humorous and nonhumorous materials by left and right brain-damaged patients.
Right hemisphere-damaged (RHD) and left hemisphere-damaged (LHD) aphasic patients were tested on a nonverbal cartoon completion task that included a humorous (Joke) and a nonhumorous (Story) condition. In both conditions, RHD patients performed worse than LHD patients. More importantly, the qualitative difference between the errors produced by the two groups suggests that right and left hemisphere brain damage impairs different components of narrative ability. RHD patients showed a preserved sensitivity to the surprise element of humor, and a diminished ability to establish coherence. Conversely, LHD patients, when they erred, showed an impaired sensitivity to the surprise element of humor, and a preserved ability to establish coherence by integrating content across parts of a narrative. These results suggest that the observed humor comprehension deficits of RHD patients result specifically from right hemisphere disease and not from brain damage irrespective of locus. The performances of the RHD and LHD patients groups together support a separation of narrative ability from the traditional aspects of language ability typically disrupted in aphasia.


Examining intra-individual variability in food-related inhibitory control and negative affect as predictors of binge eating using ecological momentary assessment.
Binge eating presents in the context of several eating disorders (EDs) and has been shown to be associated with negative affectivity and inhibitory control deficits. While considerable ecological momentary assessment (EMA) work in EDs has demonstrated the importance of intra-individual variability in affect in predicting binge episodes, no research has considered how fluctuations in inhibitory control and negative affect together influence binge eating, or the extent to which these relationships may differ across ED diagnoses. Therefore, the present EMA study assessed the extent to which daily inhibitory control moderated momentary associations between negative affect and binge eating, and whether the presence of regular compensatory behaviors influenced these associations. Participants were 40 women reporting regular binge eating (anorexia nervosa binge-purge type [AN-BP], bulimia nervosa [BN], binge-eating disorder [BED]/subthreshold BED) who completed a 10-day EMA protocol that included measures of affect, eating, and a daily ambulatory Go/No-go task that included palatable food and neutral stimuli. Results of generalized estimating equations indicated greater between-person food-related inhibitory control deficits were associated with greater binge likelihood, and there was a three-way interaction between momentary negative affect, daily food-related inhibitory control, and compensatory behavior group. For individuals with BN or AN-BP, the relationship between momentary negative affect and subsequent binge eating was stronger on days characterized by reduced inhibitory control, whereas no main or interactive effects of negative affect or inhibitory control were observed for those with BED/subthreshold BED. Together these results demonstrate the importance of intra-individual variability in executive functioning and affective processes that underlie binge eating, as well as meaningful individual differences in these momentary associations.


[Topographical diagnosis of facial paralysis (Bell's palsy) (author's transl)].
Topographical diagnosis using Schirmer's test and measurement of the stapes reflex was carried out in a series of 45 cases of Bell's palsy. The aim of this study was to define the exact location of the nerve lesion in order to guide the possible choice of surgical decompression of the facial nerve. The authors noted the existence of a geniculate or suprageniculate lesion in 62% of cases. A study of the literature shows marked disagreement between the various publications. This leads to discussion of the value and interpretation of topographical tests.


Treatment of fallopian tube metastasis in cervical cancer after laparoscopic ovarian transposition.
A 40-year-old woman, gravida 2, para 2, with squamous cell carcinoma of the cervix, stage IIB, underwent ovarian transposition. Bilateral salpingectomy was performed as part of the operative technique. Histopathologic analysis revealed mucosal spread of the tumor to one of the fallopian tubes. The patient underwent radiation of the ovaries in their new location in addition to standard chemoradiotherapy to the pelvis. There has been no evidence of disease for more than 5 years. Inasmuch as performance of bilateral salpingectomy in ovarian transposition is not standard practice, the finding of fallopian tube metastasis presented a dilemma to the clinician. It remains to be proved whether the finding of metastasis to the fallopian tubes can be evidence for ovarian metastasis in grossly normal-appearing ovaries to validate this practice. Literature review demonstrates that fallopian tube metastasis is usually associated with endometrial involvement.


Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells.
Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak- STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.


Characteristics of rhythmic jaw movements of the rabbit.
The jaw-movement pattern of the rabbit during chewing foods of different consistency was analysed. The basic movement trajectory on the frontal plane showed a crescent loop, irrespective of the food type. Difference in food consistency exerted only minor effects on the maximum gape, extent of lateral excursion and the chewing rate. These parameters of jaw movement and also the duration of a single masticatory cycle (TCL) appeared to change with physical properties other than the hardness of food. On the other hand, the number of chewing cycles in a masticatory sequence increased with increasing the hardness of food. The TCL ranged between 250 and 300 ms (frequency: 3.3-4 Hz). When a single masticatory cycle was divided into three phases (opening, closing and power phases), the TCL depended more on the duration of the opening phase than that of other two phases.


Mammae erraticae: a case report and reappraisal of the related theories.
Extra nipples and breast tissue outside the orthotopic location of the mammary glands are called polythelia and polymastia, respectively. Although the theory of mammary ridge remnants can explain extra breast tissue along the milk line, other locations such as the dorsum of the body still need further discussion. This report describes a 28-year-old Caucasian woman with a perfectly formed breast together with a meningocele in the lumbar region. Kyphoscoliosis and growth retardation were accompanying pathologies. As far as the authors can discern, this is the first case in the literature showing a well-formed breast and dysraphism occurring together. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.


Single B-Cell Genomic Analyses Differentiate Vitreoretinal Lymphoma from Chronic Inflammation.
To test whether analyzing DEPArray (Menarini Silicon Biosystems) isolated single B cells from the vitreous fluid can reveal crucial genomic and clinicopathological features to distinguish patients with vitreoretinal lymphoma (VRL) from those with chronic inflammation using immunoglobulin heavy chain (IGH), disease biomarker myeloid differentiation primary response 88 (MYD88)L265P mutation, and copy number profiling. A single-center, retrospective study. Remnant vitreous biopsies from 7 patients with VRL and 4 patients with chronic inflammation were acquired for molecular analysis. Vitreous fluid samples were prefixed in PreservCyt (Hologic) and underwent cytologic analysis and immunohistochemistry examination. Single cells were isolated using the DEPArray NxT system, followed by downstream genomic analysis. The frequencies of the dominant IGH and MYD88L265P mutation and the genome-wide copy number aberration (CNA) profiles of individual vitreous-isolated B cells were characterized. An average of 10 to 13 vitreous B cells were used in the single-cell IGH and MYD88 analyses. Higher frequencies of dominant IGH (88.8% ± 13.2%) and MYD88L265P mutations (35.0% ± 31.3%) were detected in patients with VRL than in patients with chronic inflammation (65.9% ± 13.4% and 1.5% ± 2.6% for IGH and MYD88L265P, respectively). In a cytology-proven VRL case, all 15 vitreous isolated B cells were derived from the same clone with 100% paired IGH: immunoglobulin light chain (IGK) sequences. Genome-wide copy number profiling revealed a high degree of similarity between B cells from the same patient with VRL, with extensive gains and losses at the same areas across the whole genome. In addition, 14 of 15 B cells showed a BCL2/JH t(14;18) translocation, confirming cellular malignancy with a clonal origin. Clustering analysis of the copy number profiles revealed that malignant B cells derived from different patients with VRL had no common genome-wide signatures. Single B-cell genomic characterization of the IGH, MYD88L265P mutation, and copy number profile enables VRL diagnosis. Because our study involved only a small cohort, these meaningful proof-of-concept data now warrant further investigation in a larger patient cohort.


Better than nothing: A historical account of placebos and placebo effects from modern to contemporary medicine.
Throughout the history of medicine, multiple conceptions of "placebo" and "placebo effect" have often co-existed across different domains, and today the meaning of these concepts is still disputed. Against this background, this chapter provides a succinct account of the key events in the history of the concepts of "placebo," "placebo control," and "placebo effect." The first section reconstructs the etymology of the term "placebo" and its first introduction in medicine. The next sections provide an account of how placebos have been employed in both medical practice and scientific research in modern medicine. Later sections trace the emergence of the concepts of "placebo control" and "placebo effect" in the first half of the 20th century, from the first empirical studies investigating the effects of placebos up to the publication of Beecher's landmark article "The Powerful Placebo." Finally, the last two sections review the varieties of randomized, placebo-controlled trials (RCTs) in the second half of the 20th century, and the subsequent wave of empirical studies that, starting from the 1970s, have investigated the psychological, pharmacological and neurobiological mechanisms of placebo effects.


Biomechanical effects of hyper-dynamic cerebrospinal fluid flow through the cerebral aqueduct in idiopathic normal pressure hydrocephalus patients.
Normal pressure hydrocephalus (NPH) is an intracranial disease characterized by an abnormal accumulation of cerebrospinal fluid (CSF) in brain ventricles within the normal range of intracranial pressure. Most NPH in aged patients is idiopathic (iNPH) and without any prior history of intracranial diseases. Although an abnormal increase of CSF stroke volume (hyper-dynamic CSF flow) in the aqueduct between the third and fourth ventricles has received much attention as a clinical evaluation index in iNPH patients, the biomechanical effects of this flow on iNPH pathophysiology are poorly understood. This study aimed to clarify the potential biomechanical effects of hyper-dynamic CSF flow through the aqueduct of iNPH patients using magnetic resonance imaging-based computational simulations. Ventricular geometries and CSF flow rates through aqueducts of 10 iNPH patients and 10 healthy control subjects were obtained from multimodal magnetic resonance images, and these CSF flow fields were simulated using computational fluid dynamics. As biomechanical factors, we evaluated wall shear stress on the ventricular wall and the extent of flow mixing, which potentially disturbs the CSF composition in each ventricle. The results showed that the relatively high CSF flow rate and large and irregular shapes of the aqueduct in iNPH resulted in large wall shear stresses localized in relatively narrow regions. Furthermore, the resulting CSF flow showed a stable cyclic motion in control subjects, whereas strong mixing during transport through the aqueduct was found in patients with iNPH. These findings provide further insights into the clinical and biomechanical correlates of NPH pathophysiology.


Epidermal nicotinamide adenine dinucleotides in psoriasis and neurodermatitis (lichen simplex hypertrophicus).
Epidermal nicotinamide adenine dinucleotides were measured in subcorneal and basal epidermal layers in patients with psoriasis and neurodermatitis and in healthy controls. Lowry's microtechniques utilizing enzymatic cycling were used. The total NAD content in these groups was except for the involved psoriatic skin about 1.1 mmoles/kg dry weight. Between 40 and 50% of this content consisted of the reduced form. In the involved psoriatic skin the total NAD content was increased to 1.5 mmoles/kg, this increase being mainly due to a rise in NAD+. There was no difference in NAD content between epidermal layers in the various groups studied. The total NADP content was near 0.15 mmoles/kg in healthy controls and in patients with neurodermatitis. The subcorneal layers contained 10% more of the dinucleotide than the basal layers, but in the two layers the reduced form amounted to about 80% of the total. In both non-involved and involved skin of the psoriatic patients the total NADP content was significantly increased above the control level, by up to 20% in the former and up to 65% in the latter. In the two layers studied the NADP+ content was increased by about 75% in both non-involved and involved areas. In contrast, the NADPH content rose only in the basal layers of the lesion, by 55%. The increased levels of NADP+ and NADPH found in psoriasis might suggest an accelerated or differently conducted NADPH dependent biosynthesis in this disease.


Radiation therapy and antiangiogenic therapy: Opportunities and challenges.
The importance of tumoral vascularization as a therapeutic target was first described in 1971 by Folkman. Anarchic vascularization in response to tumour hypoxia, especially mediated by vascular endothelial growth factor, represents a major target in the management of many cancers. The contribution of systemic anti-angiogenic treatments including humanized anti-VEGF monoclonal antibodies (bevacizumab) and tyrosine kinase inhibitors, whose effect on vascular normalization and correction of tumour hypoxia has been shown in preclinical studies to be enhancing the effect of radiotherapy. Early trials combining radiotherapy and antiangiogenics with a small number of patients have contradictory results and tend to put into perspective the opportunity that this synergistic association represents. The efficiency found must be tempered by some toxicity described, especially in association with high doses per fraction. The aim of this article is to present the main studies reporting the efficiency and safety of the combination of antiangiogenic drugs and radiotherapy, as well as the expected opportunities.


Seeking Extremes in Molecular Design: To What Extent May Two "Non-Bonded" Hydrogen Atoms be Squeezed in a Hydrocarbon?
A series of novel and possibly synthetically accessible rigid hydrocarbon structures is computationally introduced, maintaining ultrashort non-bonded hydrogen-hydrogen (H⋅⋅⋅H) contacts smaller than 1.2 Å. These are the shortest non-bonded H⋅⋅⋅H contacts reported to date, bypassing previous world records of both experimentally observed, 1.56 Å, and computationally derived, 1.4 Å, H⋅⋅⋅H contacts in any stable molecular structure.


Properties of the basal calcium influx in human red blood cells.
The basal (45)Ca(2+) influx in human red blood cells (RBC) into intact RBC was measured. (45)Ca(2+) was equilibrated with cells with t(1/2)=15-20 s and the influx reached the steady state value in about 90-100 s and the steady state level was 1.5+/-0.2 micromol/l(packed cells) (n=6) at 37 degrees C. The average value of the Ca(2+) influx rate was 43.2+/-8.9 micromol/l(packed cells) hour. The rate of the basal influx was pH-dependent with a pH optimum at pH 7.0 and on the temperature with the temperature optimum at 25 degrees C. The basal Ca(2+) influx was saturable with Ca(2+) up to 5 mmol/l but at higher extracellular Ca(2+) concentrations caused further increase of basal Ca(2+) influx. The (45)Ca(2+) influx was stimulated by addition of submicromolar concentrations of phorbol esters (phorbol 12-myristate-13-acetate (PMA) and phorbol-12,13-dibutyrate (PDBu)) and forskolin. Uncoupler (3,3',4',5-tetrachloro-salicylanilide (TCS) 10(-6)-10(-5) mol/l) inhibited in part the Ca(2+) influx. The results show that the basal Ca(2+) influx is mediated by a carrier and is under control of intracellular regulatory circuits. The effect of uncoupler shows that the Ca(2+) influx is in part driven by the proton-motive force and indicates that the influx and efflux of Ca(2+) are coupled via the RBC H(+) homeostasis.


A multi-time-scale analysis of chemical reaction networks: II. Stochastic systems.
We consider stochastic descriptions of chemical reaction networks in which there are both fast and slow reactions, and for which the time scales are widely separated. We develop a computational algorithm that produces the generator of the full chemical master equation for arbitrary systems, and show how to obtain a reduced equation that governs the evolution on the slow time scale. This is done by applying a state space decomposition to the full equation that leads to the reduced dynamics in terms of certain projections and the invariant distributions of the fast system. The rates or propensities of the reduced system are shown to be the rates of the slow reactions conditioned on the expectations of fast steps. We also show that the generator of the reduced system is a Markov generator, and we present an efficient stochastic simulation algorithm for the slow time scale dynamics. We illustrate the numerical accuracy of the approximation by simulating several examples. Graph-theoretic techniques are used throughout to describe the structure of the reaction network and the state-space transitions accessible under the dynamics.


Deregulation of the histone demethylase JMJD2A is involved in human carcinogenesis through regulation of the G(1)/S transition.
Although a number of JmjC-containing histone demethylases have been identified and biochemically characterized, pathological roles of their dysfunction in human disease such as cancer have not been well elucidated. Here, we report the Jumonji domain containing 2A (JMJD2A) is integral to proliferation of cancer cells. Quantitative real-time PCR analysis revealed higher expression of JMJD2A in clinical bladder cancer tissues than in corresponding non-neoplastic tissues (P<0.0001). Immunohistochemical analysis also showed positive staining for JMJD2A in 288 out of 403 lung cancer cases, whereas no staining was observed in lung normal tissues. Suppression of JMJD2A expression in lung and bladder cancer cells overexpressing this gene, using specific siRNAs, inhibited incorporation of BrdU and resulted in significant suppression of cell growth. Furthermore, JMJD2A appears to directly transactivate the expression of some tumor associated proteins including ADAM12 through the regulation of histone H3K9 methylation. As expression levels of JMJD2A are low in normal tissues, it may be feasible to develop specific inhibitors targeting the enzyme as anti-tumor agents which should have a minimal risk of adverse reaction.


Anomaly of the internal carotid artery detected during tonsillectomy.
The blood vessel anomalies of the head-neck area may result in death with massive hemorrhage during head and neck surgery. Although anomalies of internal carotid artery (ICA) are observed particularly on the posterior pharyngeal wall, we may confront them in various localizations. Because of these anomalies, the surgeon must always be aware of this risk during tonsillectomy, adenoidectomy, and uvulopalatopharyngoplasty operations. In our case, an S curling-type anomaly of the ICA has been discovered in the distance of 1 cm to the left tonsil during tonsillectomy. Protecting the ICA, a careful tonsillectomy has been performed by using thermal welding and cold dissection method. Then, anomaly has been confirmed radiologically by angiography. This document emphasizes the fact that the surgeon must provide against vascular anomalies that may be confronted during head-neck surgery and that the preoperative examinations should be assessed within this frame.


miRNAs orchestration of cardiovascular diseases - Particular emphasis on diagnosis, and progression.
MicroRNAs (miRNAs; miRs) are small non-coding ribonucleic acids sequences vital in regulating gene expression. They are significant in many biological and pathological processes and are even detectable in various body fluids such as serum, plasma, and urine. Research has demonstrated that the irregularity of miRNA in multiplying cardiac cells is linked to developmental deformities in the heart's structure. It has also shown that miRNAs are crucial in diagnosing and progressing several cardiovascular diseases (CVDs). The review covers the function of miRNAs in the pathophysiology of CVD. Additionally, the review provides an overview of the potential role of miRNAs as disease-specific diagnostic and prognostic biomarkers for human CVD, as well as their biological implications in CVD.


Experimental chemotherapy of Schistosoma curassoni in mice.
Mice experimentally infected with Schistosoma curassoni were treated with different dose regimens of praziquantel, metrifonate, oxamniquine and hycanthone. Praziquantel was the most effective drug; a dose of 100 mg/kg given orally for 5 days resulted in a 95% reduction in worm burdens. The drug produced oogram changes in all animals. Metrifonate did not result in a reduced worm burden but caused oogram changes even on a low-dose (150 mg/kg during 2 consecutive days) schedule. Oxamniquine proved to be ineffective; no reduction in worm burdens or alterations in oograms were observed. Hycanthone (80 mg/kg for 1 day) resulted in a significant reduction in worm burdens.


Mortality risk factors of Acinetobacter baumannii bacteraemia.
Acinetobacter baumannii is one of the most important nosocomial pathogens, and its multiple antibiotic resistance has emerged as an obstacle in the treatment of these infections worldwide. To identify risk factors of mortality for A. baumannii bacteraemia. A retrospective cohort study of 72 patients with significant A. baumannii bacteraemia was conducted to evaluate risk factors for mortality. The median age of the 72 enrolled patients was 48 years, 96% of the cases were hospital-acquired, and the bacteraemia-related mortality rate was 29% (21 of 72 patients). Univariate analysis revealed that the risk factors for mortality included: an elevated acute physiology and chronic health evaluation (APACHE II) score, receipt of in vitro ineffective definitive antimicrobial therapy, in vitro A. baumannii resistance to cefoperazone/ sulbactam, neutropenia, and presentation with septic shock. Multivariate analysis reveals that the independent risk factors for mortality are neutropenia and elevated APACHE II scores. Risk factors such as neutropenia and elevated APACHE II scores are found to be associated with higher mortality rates of A. baumannii bacteraemia. Further study is necessary for the determination of optimal strategies for both the prevention and treatment of these infections.


Metabolic and proteomic signatures of type 2 diabetes subtypes in an Arab population.
Type 2 diabetes (T2D) has a heterogeneous etiology influencing its progression, treatment, and complications. A data driven cluster analysis in European individuals with T2D previously identified four subtypes: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild obesity-related (MOD), and mild age-related (MARD) diabetes. Here, the clustering approach was applied to individuals with T2D from the Qatar Biobank and validated in an independent set. Cluster-specific signatures of circulating metabolites and proteins were established, revealing subtype-specific molecular mechanisms, including activation of the complement system with features of autoimmune diabetes and reduced 1,5-anhydroglucitol in SIDD, impaired insulin signaling in SIRD, and elevated leptin and fatty acid binding protein levels in MOD. The MARD cluster was the healthiest with metabolomic and proteomic profiles most similar to the controls. We have translated the T2D subtypes to an Arab population and identified distinct molecular signatures to further our understanding of the etiology of these subtypes.


Combination of the anti-CD30-auristatin-E antibody-drug conjugate (SGN-35) with chemotherapy improves antitumour activity in Hodgkin lymphoma.
The antibody-drug conjugate (ADC) cAC10-vcMMAE consists of the tubulin inhibitor monomethyl auristatin E (MMAE) conjugated to the chimeric anti-CD30 monoclonal antibody cAC10. This ADC potently interferes with the growth of CD30-positive haematological tumours, including Hodgkin lymphoma (HL) and anaplastic large-cell lymphoma. This study found improved antitumour activity in a preclinical model of HL when SGN-35 was combined with chemotherapeutic regimens such as ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or gemcitabine. Improved efficacy was also observed in high tumour burden models, indicating that combining ADCs with chemotherapeutic agents may be advantageous for the treatment of patients with relapsed or refractory HL.


Translational control by long non-coding RNAs.
Long non-coding (lnc) RNAs, once considered as junk and useless, are now broadly recognized to have major functions in the cell. LncRNAs are defined as non-coding RNAs of more than 200 nucleotides, regulate all steps of gene expression. Their origin is diverse, they can arise from intronic, intergenic or overlapping region, in sense or antisense direction. LncRNAs are mainly described for their action on transcription, while their action at the translational level is more rarely cited. However, the bibliography in the field is more and more abundant. The present synopsis of lncRNAs involved in the control of translation reveals a wide field of regulation of gene expression, with at least nine distinct molecular mechanisms. Furthermore, it appears that all these lncRNAs are involved in various pathologies including cancer, cardiovascular and neurodegenerative diseases.


Baseline and Updated Information on Nutritional Status in Patients With Chronic Limb Threatening Ischaemia Undergoing Revascularisation.
The aim of this study was to assess the impact of baseline and updated nutritional status on prognosis in patients with chronic limb threatening ischaemia (CLTI) undergoing revascularisation. The clinical database of the Surgical reconstruction versus Peripheral INtervention in pAtients with critical limb isCHemia (SPINACH) study, a prospective, multicentre, observational study, was used. The current analysis included 499 patients who underwent endovascular therapy or surgical reconstruction for CLTI. Nutritional status at baseline was evaluated using the Geriatric Nutritional Risk Index (GNRI; baseline GNRI). A GNRI <82 points indicates major nutrition related risk. GNRI was also calculated at 1, 3, 6, 12, 24, and 36 months after revascularisation (updated GNRI). The association between baseline and updated GNRIs and the mortality risk was analysed with the Cox regression model. Mean ± standard deviation (SD) GNRI at baseline was 89.9 ± 9.8 points. The proportion of patients alive with a GNRI ≥82 points was 78% (95% confidence interval [CI] 74-81) at baseline but gradually decreased during follow up, finally reaching 19% (95% CI 0-42) at 36 months. In patients with a GNRI <82 points at baseline, a GNRI of ≥82 points was increased to 37% (95% CI 6-68) 12 months after revascularisation. In the multivariable analysis, baseline and updated GNRIs were associated with a reduced mortality risk independently of each other; the adjusted hazard ratios per 1 SD were 0.80 (95% CI 0.65-0.98; p = .031) and 0.66 (95% CI 0.49-0.91; p = .015), respectively. Similar findings were observed when nutritional status was evaluated using the Controlling Nutritional Stats (CONUT) score, except for the association between its updated value and mortality risk, which marginally lost significance. There was still room for improvement in nutritional status after revascularisation for patients with CLTI. Updated GNRI was associated with death independently of baseline GNRI.


A New Species of Vietnamella Tshernova 1972 (Ephemeroptera: Vietnamellidae) from Thailand.
The larva, male subimago, female imago, and eggs of V. nanensis sp. n. are described based on specimens from Mae Hong Son and Nan provinces, Thailand. The female subimago is described based on a photograph of a specimen reared to the imago stage. The species previously was distinguished only by DNA barcode data and designated as Vietnamella sp. C. Based on morphology, the larva of the new species can be distinguished with the following combination of characteristics: (i) pattern of serration on the ventral margin of the forefemur, (ii) posterolateral margins of abdominal terga with pairs of acute tubercles, especially terga VI and VII, (iii) a well-developed pair of median ridge projections on tergum X, (iv) the second segment of the maxillary palp being about 1.3× the length of the third segment, and (v) females containing eggs with prominent protuberances on the chorionic surface. A key to larvae of all known species in the genus is provided.


Comparing the efficacy of continuous erythropoietin receptor activator and darbepoetin Alfa treatments in Japanese patients with chronic kidney disease during the predialysis period: A propensity-matched analysis.
Erythropoiesis-stimulating agent (ESA) treatment during the predialysis period can be a strategy to reduce cardiac mortality soon after initiation of dialysis. In this study, we compared the efficacy of continuous erythropoietin receptor activator (CERA) and darbepoetin alfa (DA) in patients with chronic kidney disease (CKD) over 6 months prior to initiation of dialysis. This study was a retrospective propensity score-matched study conducted at a single center in Japan that analyzed the effects of CERA and DA therapy on haemoglobin (Hb) changes, ESA resistance index (ERI) changes, and interval of ESA administration during a 6-month observation period prior to initiation of dialysis. Propensity scores were used for matching the patients included in the CERA and DA groups. Among 680 screened, 74 pairs of patients (one in each group) were included in the present analysis after propensity score matching. Mean Hb significantly decreased over 6 months in the DA group compared to that in the CERA group (-0.70 ± 0.23 vs. -0.33 ± 0.22). In the DA group, mean ERI was significantly increased at 4, 3, 2, and 1 month before dialysis and initiation of dialysis, while in the CERA group, mean ERI was significantly increased only at 1 month before dialysis and initiation of dialysis. Moreover, patients administered CERA were required to visit the hospital significantly less frequently for ESA administration than those administered DA. Our study showed that CERA may be more effective than DA for management of anaemia during the predialysis period in CKD patients.


Metabolism of bile alcohols in the perfused rabbit liver - C26 bile alcohols.
The metabolism of a C26 bile alcohol (I, 24-nor-5beta-cho-lestane-3alpha, 7alpha,25-triol) was studied in the isolated perfused rabbit liver. The new bile alcohol and bile acid metabolites secreted into the bile were isolated and identified by a combination of TLC, GLC and GLC-MS. The following bile alcohols were found: II, 24-nor-5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol, III, 24-nor-5beta-cholestane-3alpha,7alpha,12alpha,25,26-pentol; IV, 24-nor-5beta-cholest-23-ene-3alpha,7alpha,12alpha-triol; and V, 24-nor-5beta-cholest-23-ene-3alpha,7alpha-diol. In the bile acid fraction, 24-nor-cholic acid and 3alpha,7alpha,12alpha-trihydroxy-24-nor-5beta-cholest-23-en-26-oic acid were present. The perfused nor-triol was not resistant to 12alpha-hydroxylation.


Biological characterization of Trypanosoma cruzi zymodemes: in vitro differentiation of epimastigotes and infectivity of culture metacyclic trypomastigotes to mice.
Thirty-one Trypanosoma cruzi isolates from Chile, Peru, and Bolivia were studied in their capacity to differentiate in vitro from epimastigotes to metacyclic trypomastigotes on TAU-3AAG medium. Zymodeme 1 parasites displayed the best level of differentiation, which ranges from 60 to 90% depending on the isolate. Zymodeme 2 parasites exhibited highly heterogenous differentiation rates. This differentiation method permits the obtention of large amounts of metacyclic trypomastigotes from zymodeme 1 parasites. Metacyclic trypomastigotes obtained in vitro were infective to nude Balb/c hybrid mice. Zymodeme 1 parasites produced high parasitemias in this murine model; in contrast, zymodeme 2 parasites displayed lower parasitemias. Of a total of 27 T. cruzi isolates, 20 proved to be infective to mice, 12 gave enough parasites for further studies, and 8 of these were used for biological characterization. Results are compared with the infective clone Dm28 and Tulahuén strains maintained since 1954 in mice.


Climate of Online e-Learning During COVID-19 Pandemic in a Saudi Medical School: Students' Perspective.
The circumstances of the COVID-19 lockdown offered an opportunity to develop remote educational strategies in medical education. To assess medical students' experiences with online e-learning (OeL) satisfaction, intellectual environment, and communication during the COVID-19 pandemic. A cross-sectional study was conducted at the College of Medicine, University of Bisha, Saudi Arabia. A self-administered questionnaire (21 items) was used to evaluate OeL in three domains of satisfaction (nine items), intellectual environment (seven items), and communication (five items). Students from years one to six were invited to fill out the questionnaire form with five-point Likert scale responses. Descriptive statistics, one-way analysis of variance (ANOVA), and independent t-test were used to evaluate the association between variables. Out of 237 participants, 96.6% (158 male and 71 female) responded to the questionnaire. Most students (86.5%) preferred the blackboard for their e-learning. The mean total scores were 30.18 ± 6.9 out of 45 for satisfaction, 19.67 ± 5.4 out of 25 for communication 25.43 ± 5.1 out of 35 for the intellectual environment. Over 50% of the students rated moderate scores on satisfaction and intellectual environment domains. About 85% of the students rated moderate scores in the communication domain. Male students rated higher significant scores than female students for satisfaction (31.3 ± 6.3 vs 27.6 ± 7; P < .001) and intellectual environment (26.3 ± 4.32 vs 3.5 ± 6.1; P < .001). There were no significant differences in students' responses to the tested domains related to GPA level. Significantly higher levels of scores for satisfaction (33.3 ± 5.6 vs 28.8 ± 6.9; P < .001) and communication (21.2 ± 4.5 vs 18.9 ± 5.7; P = .019) were obtained by clerkship students than pre-clerkship. Medical students' experiences with e-learning are encouraging, which might be more effective with continuous training programs for students and tutors. Although OeL is an acceptable methodology, further studies are needed to analyze its impact on the target learning outcomes and students' academic achievement.


Maternal Cardiac Assessment at 35 to 37 Weeks Improves Prediction of Development of Preeclampsia.
Preeclampsia at term accounts for half of maternal deaths from hypertensive disorders. We aimed to assess differences in maternal cardiac indices at 35+0 to 36+6 weeks' gestation between women who subsequently developed preeclampsia at term compared with those with uncomplicated pregnancy and to evaluate whether cardiac indices offer incremental prognostic value to the available screening algorithm for preeclampsia. We recruited 1602 women with singleton pregnancies who attended for a routine hospital visit at 35+0 to 36+6 weeks' gestation between April and November 2018. We recorded maternal characteristics and preeclampsia-risk-score derived from a competing risks model and measured cardiac indices. Preeclampsia developed in 3.12% (50/1602) of participants. Women with preeclampsia, compared with those without, had increased mean arterial pressure (97.6, SD, 5.53 versus 87.9, SD, 6.82 mm Hg), systemic vascular resistance (1500, interquartile range, 1393-1831 versus 1400, interquartile range, 1202-1630 PRU) and preeclampsia-risk-score (23.4, interquartile range, 9.13-40 versus 0.9, interquartile range, 0.32-3.25). Multivariable analysis demonstrated independent association between the incidence of preeclampsia and E/e' (hazard ratio, 1.19/unit [95% CI, 1.03-1.37]; P=0.018) as well as left ventricular mass indexed for body surface area (hazard ratio, 1.03/[g·m2] [95% CI, 1.003-1.051]; P=0.029). Women with E/e' ≥7.3 and left ventricular mass indexed for body surface area ≥63.2 g/m2 had an increased risk for developing preeclampsia, despite low preeclampsia-risk-score <5% (hazard ratio, 20.1 [95% CI, 10.5-38.7], P<0.001). Increased left ventricular mass and E/e' offer incremental information to available scoring systems and better stratify women at risk of developing preeclampsia at term.


Comparison of Color Fundus Photography and Multicolor Fundus Imaging for Detection of Lesions in Diabetic Retinopathy and Retinal Vein Occlusion.
To evaluate the agreement between conventional fundus photography (CFP) and multicolor fundus imaging (MFI) for the detection of lesions of diabetic retinopathy (DR) and retinal vein occlusion (RVO). Cross-sectional analysis of eyes with DR or RVO who underwent CFP and MFI. All images were independently analyzed by two observers (O1 and O2), and the evaluated lesions were classified as "present" or "absent". Then, a paired comparison between both exams of the same eye was performed, to assess which made it easier to detect the lesions. Considering DR, the agreement was substantial for cotton wool spots and photocoagulation scars for both observers (O1: κ=0.75 and κ=0.67; O2: κ=0.71 and κ=0.64, respectively) and for hard exudates for O1 (κ=0.80). These lesions were detected more frequently on MFI. Regarding RVO, the agreement was considered substantial for venous sheathing by O1 (κ=0.64) and moderate for optociliary shunts by O2 (κ=0.60). Optociliary shunts were detected more frequently in CPF by both observers and venous sheathing on MFI by O1. For microaneurysms, retinal hemorrhages, retinal neovascularization, and proliferative membranes, in DR, and retinal hemorrhages, venous engorgement, and retinal neovascularization in RVO, the agreement was almost perfect (κ>0.82). In the paired analysis, both observers considered that, in DR, microaneurysms and retinal hemorrhages were easier to detect on CFP and that retinal neovascularization, cotton wool spots, and photocoagulation scars were easier to identify on MFI. Regarding RVO, optocilliary shunts were easier to identify on CFP and venous engorgement on MFI. The agreement of MFI and CFP was substantial to almost perfect for most lesions. MFI seems better to detect cotton wool spots and photocoagulations scars in DR and venous sheathing in RVO. Optocilliary shunts seem easier to detect on CFP.


Bipyridine- and Copper-Functionalized N-doped Carbon Dots for Fluorescence Turn Off-On Detection of Ciprofloxacin.
Herein, a fluorescence turn off-on nanosensor has been successfully developed using functionalized N-doped carbon dots (N-CDs) as the label-free sensing probe for the ultrasensitive detection of Cu2+ ions first and then ciprofloxacin (CIP), one of the most commonly used antibiotics for disease control, in the presence of bipyridine. The homogeneous and narrowly distributed N-CDs with a mean size of 5.7 nm and a high quantum yield of 84% are fabricated via the hydrothermal method in the presence of citric acid and ethylenediamine as the carbon and nitrogen sources, respectively. The Cu2+ ions serve as both analyte and fluorescence quenchers in the sensing platform of N-CDs, and a good linear response to Cu2+ in the range of 0.01-0.35 μM with a limit of detection (LOD) of 0.076 nM is observed. Then, 0.35 μM Cu2+ is used as the fluorescence quencher of N-CDs to build up the fluorescence turn off-on sensing probe for the detection of CIP using bipyridine (bipy) as the linker for CIP and Cu2+ ions. The addition of CIP to the bipy-Cu@N-CD composites triggers the formation of CIP-bipy-Cu conjugate as well as the release of N-CDs, resulting in the recovery of fluorescence intensity after 6 min of incubation. The sensing probe exhibits a two-phase linear response to CIP in the concentration range of 0.05-1 and 1-50 μM with a LOD of 0.4 nM. In addition, the bipy-Cu@N-CD probe shows high sensitivity toward CIP over the 19 other interferences. Good recovery of 96-110% is also observed when 0.1-0.9 μM CIP is spiked into the real samples. Results obtained in this study clearly demonstrate a newly developed sensing platform with rapid detection of metal ions and antibiotics, which can open an avenue to develop highly efficient and robust sensing probes for the detection of metal ions, organic metabolites, and biomarkers in biological applications.


Racial Disparities in Lung Cancer Screening Among Veterans, 2013 to 2021.
Racial disparities in lung cancer screening (LCS) are often ascribed to barriers such as cost, insurance status, access to care, and transportation. Because these barriers are minimized within the Veterans Affairs system, there is a question of whether similar racial disparities exist within a Veterans Affairs health care system in North Carolina. To examine whether racial disparities in completing LCS after referral exist at the Durham Veterans Affairs Health Care System (DVAHCS) and, if so, what factors are associated with screening completion. This cross-sectional study assessed veterans referred to LCS between July 1, 2013, and August 31, 2021, at the DVAHCS. All included veterans self-identified as White or Black and met the US Preventive Services Task Force eligibility criteria as of January 1, 2021. Participants who died within 15 months of consultation or who were screened before consultation were excluded. Self-reported race. Screening completion was defined as completing computed tomography for LCS. The associations among screening completion, race, and demographic and socioeconomic risk factors were assessed using logistic regression models. A total of 4562 veterans (mean [SD] age, 65.4 [5.7] years; 4296 [94.2%] male; 1766 [38.7%] Black and 2796 [61.3%] White) were referred for LCS. Of all veterans referred, 1692 (37.1%) ultimately completed screening; 2707 (59.3%) never connected with the LCS program after referral and an informational mailer or telephone call, indicating a critical point in the LCS process. Screening rates were substantially lower among Black compared with White veterans (538 [30.5%] vs 1154 [41.3%]), with Black veterans having 0.66 times lower odds (95% CI, 0.54-0.80) of screening completion after adjusting for demographic and socioeconomic factors. This cross-sectional study found that after referral for initial LCS via a centralized program, Black veterans had 34% lower odds of LCS screening completion compared with White veterans, a disparity that persisted even after accounting for numerous demographic and socioeconomic factors. A critical point in the screening process was when veterans must connect with the screening program after referral. These findings may be used to design, implement, and evaluate interventions to improve LCS rates among Black veterans.


Development of a methodology examining the behaviours of VOCs source apportionment with micro-meteorology analysis in an urban and industrial area.
During summer 2009, online measurements of 25 Volatile Organic Compounds (VOCs) from C6 to C10 as well as micro-meteorological parameters were simultaneously performed in the industrial city of Dunkerque. With the obtained data set, we developed a methodology to examine how the contributions of different source categories depend on atmospheric turbulences, and the results provided identification of emission modes. Eight factors were resolved by using Positive Matrix Factorization model and three of them were associated with mixed sources. The observed behaviours of contributions with turbulences lead to attribute some factors with sources at ground level, and some other factors with sources in the upper part of surface layer. The impact of vertical turbulence on the pollutant dispersion is also affected by the distance between sources and receptor site.


Vaginal adenocarcinoma developing in residual pelvic endometriosis: a clinical dilemma.
The clinical history of a patient with pelvic adenocarcinoma arising in residual endometriosis is reported. Detailed literature review fails to outline an optimal treatment strategy; however, thoughts concerning staging and treatment are presented.


Differentiated brain activity in response to faces of "own" versus "unfamiliar" babies in primipara mothers: an electrophysiological study.
Experiences with one's own infant attune the parent nervous system to infant stimuli. To explore the effects of motherhood on brain activity patterns, electroencephalogram (EEG) was recorded while primipara mothers of 3- and 6-month-olds viewed images of faces of their own child and an unfamiliar but appearance-matched child. Mothers of 3- and 6-month-olds showed equivalent early-wave (N/P1 "visual" and N170 "face-sensitive") responses to own and unfamiliar baby faces but differentiating late-wave (N/P600 "familiar/ novel") activity to own versus unfamiliar infant faces. Based on 3 months experience with their own infant's face, mothers' brain patterns give evidence of distinctive late-wave (recognition) sensitivity.


C-coordinated O-carboxymethyl chitosan metal complexes: Synthesis, characterization and antifungal efficacy.
A novel type of O-carboxymethyl chitosan Schiff bases (O-CSPX) was synthesized via a condensation reaction. After the coordination reaction of cupric ions, zinc ions and nickel ions, metal complexes (O-CSPX-M) were achieved. The theoretical structure of O-CSPX-M calculated by Gaussian 09 reveals that the copper ions and nickel ions underwent dsp2 hybridization, the zinc ions underwent sp3 hybridization, and they all coordinated by the carbon atom in the p-π conjugate group. Then, the structures were confirmed by FT-IR, 1H NMR, CP-MAS 13C NMR, elemental analysis, DSC and XRD. The antifungal properties of O-CSPX-M against Phytophthora capsici (P. capsici), Gibberella zeae (G. zeae), Fusarium oxysporum (F. oxysporum) and Botrytis cinerea (B. cinerea) were evaluated at concentrations ranging from 0.05mg/mL to 0.40mg/mL. The experiments indicated that the derivatives have significantly enhanced antifungal activity after metal ions complexation compared with the original chitosan. Moreover, it was shown that 0.20mg/mL of O-CSPX-Cu can 100% inhibit the growth of P. capsici and 0.20mg/mL of O-CSPX-Ni can 87.5% inhibit the growth of B. cinerea. In addition, the phytotoxicity assay and cell viability assay were also evaluated. The experimental results may provide a novel direction for the development of metal fungicides.


Education in thyroid surgery: a matched-pair analysis comparing residents and board-certified surgeons.
Resident participation in operative procedures is mandatory in educational residency programs but remains controversial, especially in the context of patient safety. This study compared the surgical quality and outcomes of thyroidectomies performed by surgical residents (RESs) and board-certified surgeons (BCSs). This retrospective matched-pair study included patients undergoing thyroidectomies for multinodular goiter, Grave's disease and early-stage thyroid cancer that were performed by a RES with BCS supervision between 2006 and 2014. The intraoperative and postoperative course, complication rates and handling of the recurrent laryngeal nerve (RLN) and parathyroid glands were analyzed. In total, 112 thyroidectomies that were performed by a RES fulfilled the inclusion criteria and were matched 1:1 with BCS patients. We included 88 hemithyroidectomies, 80 subtotal thyroidectomies and 56 total thyroidectomies. No significant differences in the handling of the RLN or parathyroid glands, the rates of postoperative RLN palsies or the rates of hypocalcaemia were found. No intraoperative complications led to the replacement of the RES as the surgeon-in-charge. Three RES and two BCS patients experienced postoperative haemorrhages (p = 0.205), and three surgical site infections (p = 1.000) occurred in each group. The mean operative time and the length of stay did not differ significantly between the two groups. Major aspects of patient safety in thyroid surgery are not affected by resident participation. Thyroidectomies performed by RES are not significantly longer and reveal no differences in length of stay or complication rates. The economic burden of resident involvement is modest.


Completeness and consistency in recording information in the tuberculosis case register, Cambodia, China and Viet Nam.
Tuberculosis (TB) case registers in Cambodia, two provinces in China and in Viet Nam. To determine completeness and consistency of information for quarterly reports on case finding and treatment outcome. A representative sample of TB case registers was selected in Cambodia, in two provinces in China and in Viet Nam. Quarterly reports were reproduced from double-entered, validated data to determine completeness and consistency. The dataset comprised 37,635 patient records in 2 calendar years. Only 0.2%, 3.6% and 1.1% of cases, respectively, in Cambodia, the two China provinces, and Viet Nam did not allow classification for the quarterly report on case finding. If the treatment outcome was reported as cured, it was correct in 99.9%, 85.7%, and 98.5% of the respective three jurisdictions: errors were mostly due to misclassification of completion as cure. Under-reporting of failures was more frequent than over-reporting in Cambodia and Viet Nam, while in the two provinces in China 84% of reported failures did not actually meet the bacteriological criterion. This evaluation demonstrates that recording essential information is exemplary in all three countries. It will be essential to carefully supervise the ability of staff to correctly define TB treatment outcome results in all three countries.


Study on the correlation of vertebral artery dominance, basilar artery curvature and posterior circulation infarction.
Vertebral artery dominance (VAD), which is a common congenital variation of vertebral artery, may be associated with an increased risk of cerebral posterior circulation infarction (PCI). The aims of this study were to investigate the correlation of VAD with incidence and laterality of PCI, and oblige the correlation of VAD and basilar artery (BA) curvature. Incidence of separate territory infarction in posterior circulation and incidence of BA curvature were compared between 78 VAD patients and 68 controls. VA dominance, laterality of BA curvature and separate territory infarction, and their directional relationships were observed in VAD group. The incidence of BA curvature in VAD group was significantly higher than that in controls (P = 0.000). 89.7 % (35/39) of patients had an opposite directional relationship between dominant VA and BA curvature. The total incidence of PCI in VAD group was significantly higher than that in controls (P = 0.001). The incidences of posterior inferior cerebellar artery (PICA) and BA territory infarction were both significantly higher than those in controls [11.5 % (9/78) vs. 1.5 % (1/68), P = 0.016; 20.5 % (16/78) vs. 7.4 % (5/68), P = 0.024]. No differences were found in superior cerebellar artery and posterior cerebral artery territory infarction between two groups. 77.8 % (7/9) of PICA infarction were on the opposite side of dominant VA. 75.0 % (12/16) of BA infarction were on the side of dominant VA. The incidence of PCI in BA curvature patients was significantly higher than that in BA straight patients. The incidence of BA curvature is higher in VAD patients, and BA usually bends to the opposite side of dominant VA. The incidence of PCI is higher in VAD patients, especially in PICA infarction and BA infarction patients.


Adoption of Single-Port Robotic Prostatectomy: Two Alternative Strategies.
Objective: To demonstrate two distinct methods for adopting the single-port (SP) robotic surgery system for robotic-assisted laparoscopic prostatectomy (RALP) by two experienced robotic surgeons (J.D. and R.A.) and evaluate early outcomes with each strategy. Methods: The initial RALP procedures using the SP robot by two surgeons were reviewed from prospective data collection at two institutions, MD Anderson Cancer Center (MDA) and OhioHealth Dublin Methodist Hospital (DMH). Both teams adopted different strategies regarding patient selection criteria, surgical approach, use of assistant ports, performance of lymphadenectomy, postoperative discharge criteria, and having a backup robot on standby. Results: The initial 74 consecutive patients who underwent SP-RALP at MDA and DMH (n = 34 and n = 40, respectively) were reviewed. All DMH and 24 MDA patients underwent a transperitoneal (TP) approach, whereas 10 MDA patients underwent an extraperitoneal (EP) approach. Mean operative time was similar for MDA and DMH, although it was shorter in TP patients. All MDA patients underwent nerve-sparing procedures and 12% underwent pelvic lymph node dissection (PLND); however, at DMH, all patients had PLND and 55% had nerve sparing. Mean estimated blood loss was not clinically significant for either group. Length of stay was 1.1 days (range, 1-2 days) for MDA and 0.12 days (range, 0--1 day) for DMH. No major complications occurred in either group other than two lymphoceles requiring percutaneous drainage in the EP SP-RALP group. Conclusion: Two significantly different strategies for SP robot adoption allowed immediately safe and equally efficacious outcomes in the initial patients treated.


The pathology and pathogenesis of malignant atrophic papulosis (Degos' disease). A case study with reference to other vascular disorders.
The morphology and immunohistology in a case of malignant atrophic papulosis (Degos' disease), a rare vascular disorder of unknown etiology, are described. The vascular lesions affected middle class and small arteries and veins throughout the body and were histologically characterized by intimal proliferation in the absence of any appreciable inflammation. The lesions were categorized as early, intermediate or late. Early lesions consisted of cellular proliferation and edema of the intima with signs of immune complex deposition (IgM, C3). Thrombosis was occasionally present as a secondary phenomenon in the affected vessel segments. In intermediate lesions the edema decreased and smooth muscle proliferation became apparent. Late lesions consisted of acellular intimal sclerosis with hyalinization and narrowing or obliteration of the vascular lumen. The media of the vessels remained always intact. In comparing these features to the pathology and pathogenesis of other vascular disorders they resembled the vascular lesions in a murine model of lupus erythematodes in which also considerable intimal proliferation occurred with thrombotic occlusion, but without appreciable inflammation. The murine model is associated with sustained low levels of circulating immune complexes and it is tempting to assume the same for Degos' disease. The notion of an immune complex mediated non-inflammatory condition underlying this severe and often fatal vascular disorder of mainly young males may contribute to the eventual finding of a successful therapeutical regimen.


A NEW SPECIES OF MYXOBOLUS (CNIDARIA: MYXOSPOREA: MYXOBOLIDAE) FROM THE FINS OF THE WESTERN CREEK CHUBSUCKER, ERIMYZON CLAVIFORMIS (CYPRINIFORMES: CATOSTOMIDAE), FROM ARKANSAS.
Between November 2018 and December 2021, 35 juvenile and adult Western Creek Chubsuckers, Erimyzon claviformis, were collected from 5 sites in western and southern Arkansas (Ouachita and Red River drainages), and their gills, gallbladders, fins, integument, other major organs, and musculature were examined for myxozoans. The fins of 12 (34%) individuals were infected with a novel species, Myxobolus stuartae n. sp. Qualitative and quantitative morphological data were obtained from formalin-fixed preserved myxospores. Molecular data from ethanol-preserved specimens consisted of a 2,028 base pair sequence of small subunit (SSU) ribosomal DNA (rDNA) from a specimen collected in Nevada County. Three other specimens from Polk County yielded partial SSU rDNA sequences that were identical to the first sequence. Phylogenetic analyses placed M. stuartae n. sp. as sister to Myxobolus bibullatus (Kudo, 1934), both clustering with other catostomid-infecting myxobolids. This is the first fin-infecting myxozoan reported from E. claviformis.


The long-term outcome of balloon valvuloplasty for mitral stenosis.
Percutaneous mitral commissurotomy (PMC) is the treatment of choice in young patients who have favorable valve anatomy. It affords an event-free survival greater than 90% at 5 to 7 years,. Economic considerations are the main limitation of PMC in such patients, who are mainly encountered in developing countries. Mitral stenosis in older patients with less favorable valve anatomy is the most frequent presentation in Western countries. This represents a heterogeneous group, but predictive analyses are helpful in deciding who should have PMC. The main conclusion is that the prediction of immediate and late results is multifactorial. Good results can be expected in young patients with unfavorable valve anatomy who do not have a very tight stenosis, are moderately symptomatic, and in sinus rhythm. In addition, PMC may reduce the thromboembolic risk related to mitral stenosis.


Manipulations in the oxygen transport capacity of blood as a means of sensitizing tumors to radiation therapy.
Tumor response to radiation is dependent not only on the quantity of hemoglobin (Hb) available for oxygen (O2) transport but also on the position of the Hb-O2 dissociation curve (Hb affinity). Previous studies have shown that administering agents which shift the Hb-O2 dissociation curve to the right (decrease Hb affinity) sensitize tumors to radiation by reducing the fraction of radiobiologically hypoxic cells. However, there may be toxicity limitations when agents aimed at altering Hb affinity are administered directly to the host. The present studies evaluated the therapeutic benefit of shifting the Hb-O2 dissociation curve in vitro prior to the transfusion of the biochemically modified RBCs into recipient hosts. Mice were given a hemolysis agent (phenylhydrazine hydrochloride, PH) prior to transfusing RBCs with normal or altered Hb affinity. A 100 mg/kg dose of PH reduced the hematocrit to approximately 60% of control 24 hr after treatment. Tumors irradiated at this time demonstrated an increased fraction of hypoxic cells. If the hematocrit was returned to normal by transfusing mice prior to irradiation, a significant but transient reduction in the hypoxic fraction was seen. Tumor response was reduced if RBCs with elevated Hb affinity, obtained by storing the erythrocytes at 4 degrees C, were used. Alternatively, tumor sensitization was noted when animals were transfused with RBCs having decreased Hb affinities. The latter was achieved by incubating the RBCs in the presence of either clofibrate or the precursors of 2,3 diphosphoglycerate (2,3 DPG). These findings further support the notion that the Hb affinity is an important parameter in determining tumor response to radiation and suggest that this factor ought to be considered when RBCs are used to transfuse anemic patients undergoing radiotherapy.


Toward in Vitro Production of Platelet from Induced Pluripotent Stem Cells.
Platelets (PLTs) are small anucleate blood cells that release from polyploidy megakaryocytes(MKs). PLT transfusion is standard therapy to prevent hemorrhage. PLT transfusion is donor-dependent way which have limitations including the inadequate donor blood supply, poor quality, and issues related to infection and immunity. Overcoming these obstacles is possible with in vitro production of human PLTs. Currently several cells have been considered as source to in vitro production of PLTs such as hematopoietic stem cells (HSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). However, HSCs are a limited source for PLT production and large-scale expansion of HSC-derived PLT remains difficult. Alternative sources can be ESCs which have unlimited expansion capacity. But ESCs have ethical issues related to destroying human embryos. iPSCs are considered as an ideal unlimited source for PLT production. They are able to differentiate into any cells and have the capacity of self-renewal. Moreover, iPSCs can be acquired from any donor and easily manipulated. Due to new advances in development of MK cell lines, bioreactors, feeder cell-free production and the ability of large scale generation, iPSC-based PLTs are moving toward clinical applicability and considering the minimal risk of alloimmunization and tumorigenesis of these products, there is great hopefulness they will become the standard source for blood transfusions in the future. This review will focus on how to progress of in vitro generation of PLT from stem cell especially iPSCs and some of the successful strategies that can be easily used in clinic will be described.


Medication compliance and comorbid substance abuse in schizophrenia: impact on community survival 4 years after a relapse.
This prospective study examined the effect of medication compliance and substance abuse on 4 year outcome in 99 patients following a relapse of schizophrenia. Univariate survival analysis revealed longer community tenure in patients if they were over the age of 35 years, not admitted 2 years prior to the index episode, remained medication compliant and did not abuse substances during the follow-up interval. Comparisons between patients grouped according to medication compliance and current substance abuse indicated that those patients who regularly took their medication but also abused substances were readmitted to hospital sooner (median survival, 10 months) compared to compliant patients who did not use substances (37 months). For noncompliant patients, time to first readmission was shorter for patients with a dual diagnosis (5 months) compared to patients with a singular diagnosis of schizophrenia (10 months). Over the 4 year period, noncompliant patients with a dual diagnosis (n=28) accounted for 57% of all hospital readmissions for the cohort and averaged 1.5 admissions per patient year. These data indicate that much of the benefit that antipsychotic medication has on increasing community survival is reduced by substance abuse. This interval is further reduced in patients who are both substance abusers and noncompliant with medication resulting in a revolving door situation of frequent hospital admissions. Integrated treatment programs which address these issues are likely to reduce the need for hospital readmission in patients with a dual diagnosis.


Safety of Sacral Nerve Stimulation in Pregnancy: A Literature Review.
Sacral nerve stimulation (SNS) is an FDA approved intervention for a spectrum of conditions. Women of childbearing age and those who are pregnant constitute a fair number of sufferers of overactive bladder symptoms and nonobstructive urinary retention; however, hypothesized effects of SNS on the fetus, mother, and the device limit its use in such a group of patients. We present a literature review to support possible safety of SNS in pregnancy. We reviewed a number of animal studies on effects of neuromodulation on myometrial activity and fetal abnormalities, and several case reports and series describing continued SNS as well as other related modes of neuromodulation during gestation and reported effects on the mother, fetus, and device. Studies on female mammals showed neurostimulation of myometrial tissue aided in embryo transfer and increased latency, evidence against inducing preterm labor, and follow-up of pregnant rats showed no effects on mothers or offspring. Reviewed cases adopted interrupted and uninterrupted courses of SNS until delivery. There were almost no pregnancy complications; infants were healthy at birth, delivered electively by Caesarean section close to term. One follow-up of 2 infants reported some health issues, though SNS was not concluded as a cause. Device replacement after delivery was occasionally performed for different reasons. No negative effects of SNS on fetus, mother or device were significantly reported in literature. Further studies expanding on data in the literature could place SNS therapy during pregnancy on the way for declaration as a safe practice.


Cellular delivery of relaxin-2 mRNA as a potential treatment for kidney fibrosis.
Renal fibrosis is a pathological feature of chronic kidney disease and its progression correlates with kidney function impairment. Since there are currently no specific therapies for renal fibrosis, we explored whether inducing local production of the anti-fibrotic molecule relaxin-2 in kidney cells has potential as a strategy for suppressing the development of renal fibrosis. Our study examined whether delivery of relaxin-2 mRNA to kidney cells in vitro and in vivo could inhibit mechanisms leading to renal fibrosis. Transfecting relaxin-2 mRNA into cultured kidney cells inhibited fibrotic responses to TGF-β1 in an autocrine or paracrine manner by reducing fibrotic gene expression in kidney tubules, and reducing proliferation in kidney fibroblasts and mesangial cells. Similarly, cubosomes assisted delivery of relaxin-2 mRNA to mouse kidneys alleviated the fibrosis and inflammation associated with renal injury following unilateral ureter obstruction (UUO). Therefore, relaxin-2 mRNA exhibits potential as a novel therapy for inhibiting fibrosis and inflammation in chronic kidney disease.


Treatment of oral and pharyngeal dysphagia.
Research on treatment of oropharyngeal dysphagia has supported several treatment approaches. Treatment can include postural changes, heightening preswallow sensory input, voluntary swallow maneuvers, and exercises. Evidence to support the efficacy of these procedures is variable. An instrumental study of a patient's oropharyngeal swallow forms the basis for treatment selection.


Modulation of large-scale brain networks by transcranial direct current stimulation evidenced by resting-state functional MRI.
Brain areas interact mutually to perform particular complex brain functions such as memory or language. Furthermore, under resting-state conditions several spatial patterns have been identified that resemble functional systems involved in cognitive functions. Among these, the default-mode network (DMN), which is consistently deactivated during task periods and is related to a variety of cognitive functions, has attracted most attention. In addition, in resting-state conditions some brain areas engaged in focused attention (such as the anticorrelated network, AN) show a strong negative correlation with DMN; as task demand increases, AN activity rises, and DMN activity falls. We combined transcranial direct current stimulation (tDCS) with functional magnetic resonance imaging (fMRI) to investigate these brain network dynamics. Ten healthy young volunteers underwent four blocks of resting-state fMRI (10-minutes), each of them immediately after 20 minutes of sham or active tDCS (2 mA), on two different days. On the first day the anodal electrode was placed over the left dorsolateral prefrontal cortex (DLPFC) (part of the AN) with the cathode over the contralateral supraorbital area, and on the second day, the electrode arrangement was reversed (anode right-DLPFC, cathode left-supraorbital). After active stimulation, functional network connectivity revealed increased synchrony within the AN components and reduced synchrony in the DMN components. Our study reveals a reconfiguration of intrinsic brain activity networks after active tDCS. These effects may help to explain earlier reports of improvements in cognitive functions after anodal-tDCS, where increasing cortical excitability may have facilitated reconfiguration of functional brain networks to address upcoming cognitive demands.


Characterization and occurrence of squash chlorotic leaf spot virus, a tentative new torradovirus infecting cucurbits in Sudan.
During a survey conducted in Sudan in 2012, a virus with spherical particles was isolated from a squash plant showing chlorotic leaf spots. The virus was transmitted mechanically and by two whitefly species, but not by aphids. RT-PCR with generic torradovirus primers yielded a band of expected size from total RNA of a symptomatic plant. Next-generation sequencing confirmed that this is tentatively a new torradovirus, for which we propose the name 'squash chlorotic leaf spot virus'. Using specific RT-PCR primers, the virus was detected in cucurbit samples collected since 1992 at different locations in Sudan.


Correlation of central corneal thickness measurements using Topcon TRK-1P, Zeiss Visante AS-OCT and DGH Pachmate 55 handheld ultrasonic pachymeter.
Corneal pachymetry is an important aspect of modern eye care. This study aims to compare the measurement of central corneal thickness (CCT) using automated optical pachymetry, anterior segment optical coherence tomography (AS-OCT) and ultrasound. Fifty volunteers participated in this study. Central corneal thickness was measured using the Topcon TRK-1P (Topcon, Tokyo, Japan) automated optical pachymeter, the Visante AS-OCT (Carl Ziess Meditec, Dublin, CA, USA) and the Pachmate 55 handheld ultrasonic pachymeter (DGH, Exton, PA, USA). Pearson correlation coefficients were calculated to compare automated optical pachymetry and AS-OCT with ultrasound. Bland-Altman plots were generated and limits of agreement (LOA) calculated. Fifty eyes were measured for comparison. The mean and standard deviation of the CCT measured by optical pachymetry was 523.7 ± 42.3 μm (range: 412 to 594), 536.0 ± 36.9 μm (range: 425 to 607) for AS-OCT and 553.4 ± 40.7 μm (range: 431 to 630) for ultrasound. Comparison of optical pachymetry and AS-OCT with ultrasound, generated Pearson correlation coefficients of 0.96 and 0.98, respectively. Measurements using optical pachymetry and AS-OCT were consistently lower than when measuring with ultrasound. Bland-Altman plots revealed mean differences of 29.7 μm between optical pachymetry and ultrasound (LOA -5.4 to -54.1) and of 17.4 μm (LOA +0.9 to -35.7) between AS-OCT and ultrasound. Due to AS-OCT and automated optical pachymetry consistently measuring lower than ultrasound, it should be noted that these devices are not interchangeable in clinical practice.


The role of miRNAs in regulating gene expression networks.
MicroRNAs (miRNAs) are key regulators of gene expression. They are conserved across species, expressed across cell types, and active against a large proportion of the transcriptome. The sequence-complementary mechanism of miRNA activity exploits combinatorial diversity, a property conducive to network-wide regulation of gene expression, and functional evidence supporting this hypothesized systems-level role has steadily begun to accumulate. The emerging models are exciting and will yield deep insight into the regulatory architecture of biology. However, because of the technical challenges facing the network-based study of miRNAs, many gaps remain. Here, we review mammalian miRNAs by describing recent advances in understanding their molecular activity and network-wide function.


A case of dyskinesia after levetiracetam administration.
Antiepileptic drug (AED) induced dyskinesia is an unusual manifestation in the medical field. In the previous case reports describing first generation-AED related involuntary movements, the authors suggested that a plausible cause is pharmacokinetic interactions between two or more AEDs. To date, development of dyskinesia after levetiracetam (LEV) has not been reported. A 28-year-old woman with a history of brain metastasis from spinal cord glioblastoma presented with several generalized tonic-clonic seizures without restored consciousness. LEV was administered intravenously. Thereafter no more clinical or electroencephalographic seizures were noted on video-EEG monitoring, while chorea movement was observed in her face and bilateral upper limbs. To our knowledge, there is no case report of dyskinesia after administration of LEV. Considering the temporal relationship and absence of ictal video-EEG findings, we suggest that development of choreoathetosis was closely associated with the undesirable effects of LEV. We propose that dopaminergic system dysregulation and genetic susceptibility might underlie this unusual phenomenon after LEV treatment.


Covalent coupling of sugars to liposomes.
A procedure is described for the covalent coupling of p-aminophenyl-alpha-D-mannopyranoside, in the presence of carbodiimide, to a derivative of phosphatidylethanolamine (N-glutarylphosphatidylethanolamine) incorporated into the bilayers of multilamellar liposomes prepared by the dehydration-rehydration method. It appears that much of the phospholipid derivative exposed on the surface of the outer liposomal bilayer interacts with the aminosugar. The procedure is simple, does not destabilize liposomes and could be applied to other receptor-specific aminosugars.


Should we routinely transfuse platelet for immune thrombocytopenia patients with platelet count less than 10 × 10⁹/L who underwent laparoscopic splenectomy?
Laparoscopic splenectomy (LS) is considered as the gold standard procedure for patients with immune thrombocytopenia (ITP). In many institutions, platelet counts less than 10 × 10(9)/L contraindicate LS. This study aimed to investigate the safety and feasibility of LS for ITP patients with platelet counts less than 10 × 10(9)/L. A total of 88 cases of LS were performed for ITP patients from June 2010 to December 2012. The patients were prospectively divided into three groups based on their immediate preoperative platelet count: < 10 × 10(9)/L (group 1); 10 × 10(9)/L to 30 × 10(9)/L (group 2); and > 30 × 10(9)/L (group 3). We collected the patients' demographic characteristics, perioperative details, and platelet count response to surgery. The patients in the three groups had comparable demographic characteristics. Only one patient in group 1 required conversion (2.4 %). The patients in group 1 experienced more blood loss than those in group 3, but this was not statistically significant. There were no significant differences between group 2 and group 3 in terms of operating time and blood loss. No statistically significant differences were found between the three groups with regard to complications and postoperative hospital stay. It is safe and feasible to perform LS in ITP patients with platelet count less than 10 × 10(9)/L, without platelet transfusion. The indication for platelet transfusion during LS for ITP patients should be the bleeding manifestations due to thrombocytopenia other than low platelet count itself.


Multi-omics Analysis of CRISPRi-Knockdowns Identifies Mechanisms that Buffer Decreases of Enzymes in E. coli Metabolism.
Enzymes maintain metabolism, and their concentration affects cellular fitness: high enzyme levels are costly, and low enzyme levels can limit metabolic flux. Here, we used CRISPR interference (CRISPRi) to study the consequences of decreasing E. coli enzymes below wild-type levels. A pooled CRISPRi screen with 7,177 strains demonstrates that metabolism buffers fitness defects for hours after the induction of CRISPRi. We characterized the metabolome and proteome responses in 30 CRISPRi strains and elucidated three gene-specific buffering mechanisms: ornithine buffered the knockdown of carbamoyl phosphate synthetase (CarAB) by increasing CarAB activity, S-adenosylmethionine buffered the knockdown of homocysteine transmethylase (MetE) by de-repressing expression of the methionine pathway, and 6-phosphogluconate buffered the knockdown of 6-phosphogluconate dehydrogenase (Gnd) by activating a bypass. In total, this work demonstrates that CRISPRi screens can reveal global sources of metabolic robustness and identify local regulatory mechanisms that buffer decreases of specific enzymes. A record of this paper's transparent peer review process is included in the Supplemental Information.


Abstracts for the 2019 NAEMSP Scientific Assembly.
The approach to managing out-of-hospital cardiac arrest (OOHCA) has generally involved either minimal on-scene resuscitation to reduce time to arrival at hospital or extended care at the scene to increase the chance of return of spontaneous circulation (ROSC) before transport. This study compared patient outcomes across EMS agencies with respect to the duration of on-scene time. We hypothesized that EMS agencies with greater average time on-scene would have more favorable outcomes. The Cardiac Arrest Registry to Enhance Survival (CARES) was used to identify OOHCA cases, including characteristics and outcomes. EMS agencies were included if they submitted at least 80 OOHCAs from 2013 to 2017. To study outcomes based upon culture of OOHCA management, outcomes were studied by EMS agency rather than by individual patient cases. Agencies in the top and bottom quartiles of on-scene time duration were categorized as high (HOSTAs) and low on-scene time agencies (LOSTAs), respectively. Generalized estimating equation models compared HOSTAs and LOSTAs. We classified 89 agencies as HOSTAs (24,114 patients, average ≥25 minutes on scene) and 89 agencies as LOSTAs (37,297 patients, average <18.9 minutes on-scene). Among patients transported, HOSTAs were more likely to have a shockable rhythm (28.4% vs. 22.2%, OR = 1.4, 95%CI 1.2 to 1.5), a witnessed arrest (65.1% vs. 53.6%, OR = 1.7, 95% CI 1.5 to 1.9), and receive bystander CPR (41.9% vs. 37.0%, OR = 1.3, 95% CI 1.1 to 1.5) than LOSTAs, all p < 0.001. When controlling for these and other patient characteristics, including mechanical CPR device use, HOSTAs had a higher proportion of ROSC on emergency department arrival (66.7% vs. 31.1%, OR = 4.6, 95%CI 3.5 to 6.0, p < 0.001), survival to discharge for transported patients (22.3% vs. 11.2%, OR = 2.6, 95%CI 2.0 to 3.4, p < 0.001), and good neurologic outcome among survivors (84.9% vs. 78.6%, OR = 1.3, 95%CI = 1.0 to 1.7, p = 0.04) than LOSTAs. This study suggests that HOSTAs have more favorable patient outcomes compared to LOSTAs. RESULTS indicate that spending more time on-scene performing resuscitation is associated with higher rates of ROSC, survival and survival with good neurologic function.


Quantitative detection of naphthenic acids in wastewater based on superior fluorescence performance of nitrogen-rich carbon quantum dots.
With the development of the petrochemical industry, a large amount of naphthenic acids in petrochemical wastewater was accumulated in the environment, causing serious environmental pollution. Most of the commonly used methods for the determination of naphthenic acids have the characteristics of high energy consumption, complicated pretreatment, long detection cycle, and the need to send samples to analytical laboratories. Therefore, it is essential to develop an efficient and low-cost field analytical method for rapidly naphthenic acids quantify. In this study, nitrogen-rich carbon quantum dots (N-CQDs) based on natural deep eutectic solvents (NADESs) was successfully synthesized by a one-step solvothermal method. The fluorescence property of carbon quantum dots was used to achieve the quantitative detection of naphthenic acids in wastewater. The prepared N-CQDs showed excellent fluorescence and stability, showed a good response to naphthenic acids and a linear relationship in the concentration range of naphthenic acids from 0.03 to 0.09 mol‧L-1. The effect of common interferents in petrochemical wastewater on the detection of naphthenic acids by N-CQDs was investigated. The results showed that N-CQDs had good specificity for the detection of naphthenic acids. N-CQDs was applied to the naphthenic acids wastewater, and the concentration of naphthenic acids in the wastewater was successfully calculated according to the fitting equation.


Human papillomavirus vaccine and systemic lupus erythematosus.
To investigate the association between human papillomavirus (HPV) vaccination and autoimmune manifestations compatible with systemic lupus erythematosus (SLE) or SLE-like disease, the medical history of six women who presented with SLE or SLE-like disease following HPV immunization was collected. Data regarding type of vaccine, number of immunization, family and personal, clinical and serological features, as well as response to treatments were analyzed. In the reported cases, several common features were observed, such as personal or familial susceptibility to autoimmunity or adverse response to a prior dose of the vaccine, both of which may be associated with a higher risk of post-vaccination autoimmunity. Favorable response to immunosuppressant was observed in all patients. In the current study, a temporal association between immunization with HPV vaccine and the appearance of a spectrum of SLE-like conditions is reported. Additionally, among the patients described, several common features were observed that may enable better identification of subjects at risk. Further studies are required to assess the safety of immunization with the HPV vaccine in patients with autoimmune-rheumatic diseases or in subject at risk of autoimmunity as well as the potential beneficial effect of preventive immunosuppressants.


Comparisons of some bluetongue virus isolates by plaque neutralization and relatedness tests.
Seven North American bluetongue virus isolates, cloned by plaquing, and sera to five of them were reacted in a plaque neutralization test. Using a paired controls system, each virus-serum reaction was studied in terms of the regression of percent neutralization on log serum dilution. Antigen-antibody interaction terms in the analysis of effective dose estimates were used to assess the relatedness of the virus isolates. The degree of cross reactivity formed a spectrum from virtually no evidence of unrelatedness to clear antigenic differences.