Impact of Pre-existing NS5A-L31 or -Y93H Minor Variants on Response Rates in Patients Infected with HCV Genotype-1b Treated with Daclatasvir/Asunaprevir.
The combination of daclatasvir (DCV, pan-genotypic NS5A inhibitor) plus asunaprevir (ASV; NS3 protease inhibitor) is approved in Japan, Korea and other countries for the treatment of chronic hepatitis C virus (HCV) genotype (GT)-1. A high (~90 to 100%) sustained virologic response (SVR) with DCV/ASV therapy has been achieved by excluding patients infected with HCV GT-1b with baseline NS5A resistance-associated variants (RAVs) at L31 or Y93H detected by direct sequencing (DS). We set out to determine whether patients with minor variants at NS5A-L31 or -Y93H, detected by next-generation sequencing (NGS), impacted SVR rates with DCV/ASV therapy. Baseline samples from 222 interferon (IFN)-ineligible/intolerant (N = 135) and prior non-responder (N = 87) patients infected with GT-1b who were treated with DCV/ASV for 24 weeks in the Phase 3 clinical study AI447026 were prepared for NGS (Ion-Torrent platform). The prevalence of baseline NS5A RAVs and their impact on SVR when observed at ≥1% by NGS in a patient's virus population were examined. NGS and DS (sensitivity ≥20%) data were compared. The prevalence of baseline NS5A RAVs at L31 or Y93H was 29% (63/219) and 18% (39/214) by NGS and DS, respectively. SVR24 rates were comparable in patients without observed baseline L31 or Y93H polymorphisms whether assessed by NGS (96%; 148/154) or by the less sensitive DS platform (95%; 164/173). Optimal SVR rates (≥95%) to DCV/ASV treatment were achieved using DS to exclude patients infected with GT-1b with NS5A RAVs at L31 or Y93H representing ≥20% of their virus population. Exclusion by NGS of patients with minor variants in NS5A (<20%) did not enhance SVR rates. These results suggest that the presence of minor variants in NS5A does not appear to impact the overall SVR rate in patients with GT-1b treated with DCV/ASV. This study was sponsored by Bristol-Myers Squibb. ClinicalTrials.gov identifier: NCT01497834.


Rapid identification of Bartonella henselae by real-time polymerase chain reaction in a patient with cat scratch disease.
We report a localized submandibular lymph node infection in a patient with cat scratch disease. Directly performing real-time polymerase chain reaction assay on the biopsy sample, Bartonella henselae DNA was simultaneously detected and identified.


Eating healthy under work stress: A gene stress interaction model.
Some employees tend to eat less healthy food when under work stress, while others tend to maintain a healthy diet. The factors underlying these different dietary choices are not yet clear. Individual differences in people's reactions to environmental stress may help explain this phenomenon. This study proposed a Gene × Stress interaction model of dietary choice, suggesting that different dietary choices under stress may be related to DRD2 genes, which moderate the reward circuitry and have been associated with habitual use of alcohol, obesity, and eating behaviors. 12,269 employees completed genotyping of their saliva samples and questionnaires on work stress, healthy dietary intentions, and healthy dietary behaviors. Nonlinear multiple regressions were used to test the hypothesized interaction of DRD2 genes and work stress on healthy dietary intentions and healthy dietary behaviors. Individuals with higher work stress reported lower healthy dietary intentions, whereas healthy dietary behaviors exhibited an inverted U shape. DRD2 genes significantly moderated this relationship, and the above relationship was only detected among C allele carriers, whereas for the AA genotype, work stress was not associated with healthy dietary intentions or behaviors. Healthy dietary intentions and healthy dietary behaviors showed different patterns of association with work stress. The DRD2 genes helped explain the individual differences in dietary choice under work stress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assessing anhedonia in depression: Potentials and pitfalls.
The resurgence of interest in anhedonia within major depression has been fuelled by clinical trials demonstrating its utility in predicting antidepressant response as well as recent conceptualizations focused on the role and manifestation of anhedonia in depression. Historically, anhedonia has been understood as a "loss of pleasure", yet neuropsychological and neurobiological studies reveal a multifaceted reconceptualization that emphasizes different facets of hedonic function, including desire, effort/motivation, anticipation and consummatory pleasure. To ensure generalizability across studies, evaluation of the available subjective and objective methods to assess anhedonia is necessary. The majority of research regarding anhedonia and its neurobiological underpinnings comes from preclinical research, which uses primary reward (e.g. food) to probe hedonic responding. In contrast, behavioural studies in humans primarily use secondary reward (e.g. money) to measure many aspects of reward responding, including delay discounting, response bias, prediction error, probabilistic reversal learning, effort, anticipation and consummatory pleasure. The development of subjective scales to measure anhedonia has also increased in the last decade. This review will assess the current methodology to measure anhedonia, with a focus on scales and behavioural tasks in humans. Limitations of current work and recommendations for future studies are discussed.


Commitment, job satisfaction and personality: A cross sectional study of generational cohorts in nursing students.
The current domestic nursing workforce is the most generational diversity in history with a wide range of life experiences. The purpose of this study was to investigate generational differences in organizational commitment, job satisfaction and personality traits in a sample of nursing students preparing for the workforce. This cross-sectional study used data collected from pre-licensure final semester nursing students and degree completion students (n = 313) from three different schools about job satisfaction, personality traits and organizational commitment. Findings showed the scores between the generations were not significantly different for job satisfaction (p = 0.86) and organizational commitment (p = 0.40). Significant differences were found between the generations for the personality measures of agreeableness (p = 0.02), conscientiousness (p = 0.01), and emotional stability (p = 0.00). Understanding generational differences in nursing students entering the workforce can serve academia and practice partners to focus curriculum and resources appropriately to prepare the next generation of nurses for the challenges in a time of crisis.


Poly(A)-Binding Protein Regulates the Efficiency of Translation Termination.
Multiple factors influence translation termination efficiency, including nonsense codon identity and immediate context. To determine whether the relative position of a nonsense codon within an open reading frame (ORF) influences termination efficiency, we quantitate the production of prematurely terminated and/or readthrough polypeptides from 26 nonsense alleles of 3 genes expressed in yeast. The accumulation of premature termination products and the extent of readthrough for the respective premature termination codons (PTCs) manifest a marked dependence on PTC proximity to the mRNA 3' end. Premature termination products increase in relative abundance, whereas readthrough efficiencies decrease progressively across different ORFs, and readthrough efficiencies for a PTC increase in response to 3' UTR lengthening. These effects are eliminated and overall translation termination efficiency decreases considerably in cells harboring pab1 mutations. Our results support a critical role for poly(A)-binding protein in the regulation of translation termination and also suggest that inefficient termination is a trigger for nonsense-mediated mRNA decay (NMD).


The role of carbohydrate antigen 19-9 as a tumour marker of oesophageal cancer.
Carcinoma of the oesophagus is endemic in certain well demarcated areas throughout the world, and a method of screening population groups at high risk for oesophageal cancer is urgently needed. In this study the sensitivity and specificity of the carbohydrate antigen CA19-9 as a marker of carcinoma of the oesophagus in African patients was examined. The normal range was established by assay of serum samples from healthy black blood donors, using a solid phase radioimmunoassay with mouse monoclonal antibody to CA19-9 labelled with 125I. Serum concentrations of CA19-9 were then measured in 100 African patients with oesophageal cancer and 28 patients with benign oesophageal disease. The upper limit of CA19-9 in the normal controls was 40 U ml-1. Thirty-four patients with oesophageal cancer and five with benign oesophageal disease had elevated levels. Therefore, in this series, the sensitivity of CA19-9 as a marker of oesophageal cancer was 34% and the specificity was 82%. While CA19-9 is not sufficiently sensitive to be used as a screening test of oesophageal cancer, it compares favourably with other known tumour markers of this disease, and may have a role in monitoring disease recurrence and response to treatment.


Lectinohistochemistry of human bladder cancer: loss of lectin binding structures in invasive carcinomas.
With the purpose of studying changes in the expression of glycoconjugate structures in urothelium, nine different lectins (PNA, WGA, VFA, GSA II, STA, UEA I, LCA, DBA and HPA) with specificity for mono- or oligo-saccharides were used on formalin-fixed, paraffin-embedded tissue sections from 47 patients who had undergone surgical resection for bladder tumors and on normal urothelial biopsies from 10 patients. The tumors were graded and a lectinohistochemical method using biotinylated lectins and avidin-biotin-peroxidase complex was used to demonstrate the lectin binding. Positive staining reactions of cells in cytoplasm and on membranes were evaluated in the basal, the intermediate, and the luminal cell layers, respectively. In both normal and atypical urothelium lectin binding predominated in the luminal cell layer and decreased towards the basal cell layer. In normal urothelium all lectins stained greater than 66% of the cells in the luminal cell layer in cytoplasm and between 5 and 100% of the cells on membranes depending on the lectin used. A gradual loss of lectin-binding structures was seen with increasing grade of atypia. The range of this decrease varied considerably from one lectin to another, but it was consistently found that the percentage of cells stained in cytoplasm and on membranes decreased. A significantly lower percentage of cells stained in cytoplasm was found in invasive tumor cell-islands compared to normal urothelium. In invasive tumor cell-islands staining of cells on membranes was completely absent, except for HPA lectin that stained less than 10% of the cells. In conclusion, we demonstrate a dramatic decrease in lectin-binding carbohydrate structures associated with urothelial malignant progression.


Recognition and avoidance of the odors of parasitized conspecifics and predators: differential genomic correlates.
In many species of animals chemical stimuli are an important source of information about the threats and dangers present in the social and non-social world. Olfactory cues play a fundamental role in modulating social recognition and interactions in a wide variety of mammals. Rodents, in particular, utilize chemical signals, to recognize and avoid conspecifics infected with parasites and other pathogens. Animals also respond to, and utilize, predator odor related information to assess and minimize their risk of predation. In this review, we briefly focus on the relations between odors, parasite recognition and avoidance and consider some of the associated hormonal, neural and genomic mechanisms. We describe how both male and female rodents distinguish between infected and uninfected males on the basis of odors, displaying aversive response to, and avoidance of, the urine odors of infected individuals. We further describe how the recognition and avoidance of the odors of infected individuals involves genes for the neuropeptide, oxytocin, (OT), and estrogenic mechanisms. We show that mice with deletions of the oxytocin gene (OT knockout mice (OTKO)) and mice whose genes for estrogen receptor (ER)-alpha or ER-beta [ER knockout mice (ERKO), alphaERKO and betaERKO] have been disrupted are specifically impaired in their recognition, avoidance, and memory of the odors of infected individuals. We contrast this with the recognition and display of aversive responses to predator (cat) odor that are insensitive to these genetic manipulations. These findings reveal some of the mechanisms associated with the olfactory mediated recognition of parasitized individuals and predators.


Sphingosine-1-phosphate promotes the nuclear translocation of β-catenin and thereby induces osteoprotegerin gene expression in osteoblast-like cell lines.
Sphingosine-1-phosphate (S1P) is a well-known signaling sphingolipid and bioactive lipid mediator. Recently, it was reported that S1P inhibits osteoclast differentiation and bone resorption. On the other hand, S1P effects on osteoblasts and bone formation are little known. In this study, we investigated the effects of S1P on osteoblasts, using two osteoblast-like cell lines, SaOS-2 and MC3T3-E1. S1P activated phosphatidylinositol 3-kinase (PI3K)/Akt signaling, leading to the inhibition of glycogen synthase kinase-3β and the nuclear translocation of β-catenin, followed by the increase of the transcriptional activity by β-catenin/T-cell factor complex formation in both SaOS-2 cells and MC3T3-E1 cells. The inhibitors of PI3K and Akt suppressed S1P-induced nuclear localization of β-catenin. We further investigated the effects of PI3K/Akt signaling on the Wnt/β-catenin signaling pathway, since β-catenin takes a central role in this signaling pathway. Both inhibitors for PI3K and Akt suppressed the nuclear localization of β-catenin and T-cell factor transcriptional activity induced by Wnt-3a. S1P increased the amount of osteoprotegerin at both mRNA and protein levels, and increased the activity of alkaline phosphatase, leading to the mineralization. These findings suggest that S1P activates the PI3K/Akt signaling pathway leading to the promotion of nuclear translocation of β-catenin in osteoblast-like cells, resulting in the upregulation of osteoptotegerin and osteoblast differentiation markers including alkaline phosphatase, probably relating to the inhibition of osteoclast formation and the mineralization, respectively.


Posterior pilon fracture treated by opening the fibula fracture gap.
Posterior pilon fracture is a relatively common clinical fracture involving the posterior articular surface of the distal tibia. Currently, this form of fracture is receiving increasing attention. The surgical approach and technique for the treatment of posterior pilon fractures are still controversial. The purpose of this retrospective study was to compare the clinical and imaging outcomes of pilon fractures after treatment with the open fibula fracture line (OFFL) surgical technique versus the traditional posterolateral approach (TPL). A retrospective analysis of patients with posterior pilon fractures treated using the open fibula fracture line technique and the traditional posterolateral approach between January 2015 and March 2020. Thirty-one cases were included in the open fibula fracture line technique group and twenty-eight cases were included in the traditional posterolateral approach group. We used the Burwell-Charnley scale to assess the effectiveness of surgical repositioning. The clinical outcomes were evaluated using American Orthopaedic Foot & Ankle Society ankle-hind foot score (AOFAS) and visual analog score (VAS). The overall anatomic reduction rate was slightly better in the open fibula fracture line group than in the conventional posterolateral group (81% vs. 71%, p = 0.406), but there was no statistically significant difference between the two groups. There were no statistically significant differences between the two groups in terms of fracture healing time and time to full weight bearing (p > 0.05). At the final follow-up, the AOFAS functional score of the open fibula fracture line group was statistically superior to that of the conventional posterolateral group (p < 0.05). However, there was no statistical difference between the two groups in VAS pain scores at rest, during activity, and under weight bearing (p > 0.05). The trans-fibular fracture approach provides a better surgical option for specific types of posterior pilon fractures with a high rate of anatomic repositioning and a good near-term outcome. Retrospective registration.


Protective effects of mesenchymal stem cells on ischemic brain injury: therapeutic perspectives of regenerative medicine.
Cerebral ischemic injury as the main manifestation of stroke can occur in stroke patients (70-80%). Nowadays, the main therapeutic strategy used for ischemic brain injury treatment aims to achieve reperfusion, neuroprotection, and neurorecovery. Also, angiogenesis as a therapeutic approach maybe represents a promising tool to enhance the prognosis of cerebral ischemic stroke. Unfortunately, although many therapeutic approaches as a life-saving gateway for cerebral ischemic injuries like pharmacotherapy and surgical treatments are widely used, they all fail to restore or regenerate damaged neurons in the brain. So, the suitable therapeutic approach would focus on regenerating the lost cells and restore the normal function of the brain. Currently, stem cell-based regenerative medicine introduced a new paradigm approach in cerebral ischemic injuries treatment. Today, in experimental researches, different types of stem cells such as mesenchymal stem cells have been applied. Therefore, stem cell-based regenerative medicine provides the opportunity to inquire and develop a more effective and safer therapeutic approach with the capability to produce and regenerate new neurons in damaged tissues.


Orbital and ventromedial prefrontal cortex functioning in Parkinson's disease: neuropsychological evidence.
A recent paper (Zald & Andreotti, 2010) reviewed neuropsychological tasks that assess the function of the orbital and ventromedial portions of the prefrontal cortex (OMPFC). Neuropathological studies have shown that the function of the OMPFC should be preserved in the early stages of Parkinson's disease (PD) but becomes affected in the advanced stages of PD. This pattern has also been suggested by studies that have shown that dopaminergic drugs impair the performance of early PD patients in OMPFC tasks that involve reinforcement learning but enhance the performance of advanced PD patients. Based on these empirical findings, we reviewed the neuropsychological evidence of OMPFC functions in PD patients to test two hypotheses regarding the following: (1) OMPFC functions at different stages of PD; (2) different effects of dopaminergic drugs on OMPFC functions based on PD stage and task demand. We focused our review only on the neuropsychological tasks that were specific and sensitive to the functions of the OMPFC and that were adopted at different stages of PD, such as reversal learning tasks, the Iowa Gambling Task and the affective Theory of Mind task. We found robust empirical evidence that in early PD, OMPFC functions are preserved and dopaminergic drugs result in a detrimental effect when the task involves reinforcement learning. Further studies are needed to verify the status of OMPFC functions in non-demented, advanced PD and to describe the longitudinal course of OMPFC functions in this clinical population.


Effects of polyamines on higher-order folding of in situ chromatin.
Modifications of the higher-order chromatin structure induced by polyamines have been quantitatively investigated in situ through a non-invasive biophysical approach using Differential Scanning Calorimetry and Quantitative Fluorescence Microscopy. Calorimetric and intensitometric profiles have been acquired for samples of native thymocytes, alternatively suspended in buffers, with or without natural polyamines (spermine and spermidine). The results here reported show that the structure and distribution of nuclear chromatin in situ considerably change upon the ionic composition of the environment. A quantitative analysis of this data and a comparison with previous results obtained from isolated chromatin fibers was carried out. Finally, an inverse relationship between chromatin condensation and nuclear volume was observed.


Genome Sequence of an Epidemic Isolate of Mycobacterium abscessus subsp. bolletii from Rio de Janeiro, Brazil.
Multiple isolates of Mycobacterium abscessus subsp. bolletii, collectively called BRA100, were associated with outbreaks of postsurgical skin infections across various regions of Brazil from 2003 to 2009. We announce the draft genome sequence of a newly sequenced BRA100 strain, M. abscessus subsp. bolletii CRM-0020, isolated from a patient in Rio de Janeiro, Brazil.


Crossed cerebellar diaschisis: insights into oxygen challenge MRI.
Hyperoxia during T2*-weighted magnetic resonance imaging (oxygen challenge imaging (OCI)) causes T2*-weighted signal change that is dependent on cerebral blood volume (CBV) and oxygen extraction fraction (OEF). Crossed cerebellar diaschisis (CCD), where CBV is reduced but OEF is maintained, may be used to understand the relative contributions of OEF and CBV to OCI results. In subjects with large hemispheric strokes, OCI showed reduced signal change in the contralesional cerebellum (P=0.027, n=12). This was associated with reduced CBV in contralesional cerebellum (P=0.039, n=9). CCD may be a useful model to determine the relative contribution of CBV to signal change measured by OCI.


Urinary biomarkers of oxidative stress and plasmatic inflammatory profile in phenylketonuric treated patients.
Oxidative stress has been proposed as an important pathophysiologic feature of various inborn errors of metabolism, including phenylketonuria (PKU). Considering that there are few studies relating oxidative stress and inflammation directly in PKU disease, the aim of this study was to evaluate and correlate oxidative damage to biomolecules, antioxidant defenses, pro-inflammatory cytokines, phenylalanine (Phe) and its metabolites (phenyllactic acid--PLA and phenylacetic acid--PAA) levels in urine and plasma from patients with PKU under dietary treatment. We observed a marked increase of isoprostanes, which is a lipid peroxidation biomarker, in urine from these treated patients. Next, we demonstrated that protein oxidative damage, measured by di-tyrosine formation, was significantly increased in urine from PKU treated patients and that decreased urinary antioxidant capacity was also observed. Our findings concerning to the inflammatory cytokines interleukin-6 and interleukin-1β, both significantly increased in these patients, provide evidence that the pro-inflammatory state occurs. Besides, interleukin-1β was positively correlated with isoprostanes. We observed a negative correlation between interleukin-6 and interleukin-10, an anti-inflammatory cytokine. Di-tyrosine was positively correlated with Phe, which indicates oxidative damage to proteins, as well as with PAA. These findings may suggest that the protein damage may be induced by Phe and its metabolite PAA in PKU. Our results indicate that pro-oxidant and pro-inflammatory states occur and are, in part, correlated and protein oxidation seems to be induced by Phe and PPA in PKU patients.


Voltammetric and electrochemical quartz crystal microbalance studies of sulforaphane and its Zn(II) complexes.
Cyclic voltammetry (CV) and electrochemical quartz crystal microbalance (EQCM) methods were used to study the behavior of sulforaphane (SFR). To established electrochemical properties of SFR methyl-, ethyl-, 2-chloroethyl-, propyl-, butyl- and tert-butyl-isothiocyanates were examined at gold electrode. Optimal measurement parameters were established and stock solutions developed. The electrode activity of the studied compounds (cathodic peak E(p)=-0.6 V) was found to be primarily due to the oxidation of the isothiocyanate group. By the EQCM method it was found that during the reduction of SFR the mass of the electrode systematically increased in successive scans by ca. 120 ng per scan and in the mixture of SFR and Zn(2+) ions ca. 350 ng. Formation of SFR complexes with Zn(2+) ions was confirmed by EQCM and UV methods. Cyclic voltammetric method has been elaborated for SFR determination and compared with UV method.


The twitcher mouse: accumulation of galactosylsphingosine and pathology of the central nervous system.
In the twitcher mouse, a murine model of globoid cell leukodystrophy (GLD), pathological changes of various parts of the central nervous system correlated well with the concentration of galactosylsphingosine (psychosine). The development of GLD lesions was more obvious in tracts with a more rapid progression of myelination. It was suggested that accumulation of galactosylsphingosine subsequent to myelin maturation caused suicidal death of myelin forming cells.


Center of pressure displacement characteristics differentiate fall risk in older people: A systematic review with meta-analysis.
Falling is the second most prevalent cause of accidental death in the world. Currently available clinical tests to assess balance in older people are insufficiently sensitive to screen for fall risk in this population. Laboratory tests that record the center of pressure (COP) trajectory could overcome this problem but despite their widespread use, the choice of COP trajectory features for use as a biomarker of fall risk lacks consensus. This systematic review and meta-analysis aimed at identifying the best COP characteristics to predict risk of falling in older adults. More than 4000 articles were screened; 44 (7176 older adults) were included in this study. Several COP parameters emerged as good indices to discriminate fallers from non-fallers. From sensitivity analysis, Sway area per unit time, anteroposterior mean velocity, and radial mean velocity were the best traditional features. In this study, identification of older people with a high fall risk was demonstrated using quiet-standing recordings. Such screening would also be useful for routine follow-up of balance changes in older fallers in clinical practice.


Evaluation of treatment with zinc acetate hydrate in patients with liver cirrhosis complicated by zinc deficiency.
In Japan, no zinc preparation had been approved for therapeutic purposes before March 2017. Zinc acetate hydrate was recently approved for the treatment of hypozincemia. We evaluated the efficacy and safety of treatment with zinc acetate hydrate. A total of 97 patients with cirrhosis complicated by hypozincemia were treated with zinc acetate hydrate, and their serum zinc normalization rates; factors contributing to normalization; changes in blood ammonia levels; branched-chain amino acids-to-tyrosine ratios; levels of albumin, hemoglobin, alkaline phosphatase, serum copper, and iron; incidence of adverse events; improvement in subjective symptoms; and serum zinc levels taken at 3 months post-treatment were determined. The cumulative serum zinc normalization rates, when normalization was defined as achievement of a serum zinc level ≥80 μg/dL, after 2, 4, and 6 months of treatment were 64.9%, 80.3%, and 82.5%, respectively. Multivariate analysis identified an albumin level of ≥3.3 g/dL and branched-chain amino acids to tyrosine ratio of ≥3.46 as factors contributing to zinc normalization within 3 months of treatment. Treatment resulted in a significant decrease in blood ammonia and serum copper levels, and significant increases in branched-chain amino acids-to-tyrosine ratios and alkaline phosphatase levels. Seven (7.2%) patients prematurely discontinued treatment due to hypocupremia. By the end of treatment, subjective symptoms had resolved in 46.2% of patients. By 3 months post-treatment, serum zinc levels had reverted to levels close to those at baseline. Treatment with zinc acetate hydrate resulted in normalization of serum zinc levels at a high rate. The main reasons for discontinuation of treatment included hypocupremia.


Synthesis and transfection activity of new cationic phosphoramidate lipids: high efficiency of an imidazolium derivative.
In an effort to enhance the gene-transfer efficiencies of cationic lipids and to decrease their toxicities, a series of new phosphoramidate lipids with chemical similarity to cell membrane phospholipids was synthesised. These lipids contained various cationic headgroups, such as arginine methyl ester, lysine methyl ester, homoarginine methyl ester, ethylenediamine, diaminopropane, guanidinium and imidazolium. Their transfection abilities, either alone or with the co-lipid DOPE, were evaluated in HEK293-T7 cells. We found that imidazolium lipophosphoramidate 7 a/DOPE lipoplexes gave the most efficient transfection with low toxicity (15 %). The luciferase activity was 100 times higher than that obtained with DOTAP/DOPE lipoplexes. The size, zeta potential, pDNA-liposome interactions and cellular uptakes of the lipoplexes were determined. No definitive correlation between the zeta potential values and the transfection efficiencies could be established, but the uptake of lipoplexes by the cells was correlated with their final transfection efficiencies. Our results show that imidazolium phosphoramidate lipids constitute a potential new class of cationic lipids for gene transfer.


Enhancing the longevity of three-dimensional dose in a diffusion-controlled Fricke gel dosimeter.
The principle of Fricke gel dosimeter is the oxidation of ferric ions on exposure to radiation. The major limitation in this dosimeter is the post-irradiation diffusion of ferric ions leading to degradation of spatial dose information. The primary objective of this study is to reduce diffusion of ferric ions post-irradiation and enhance the spatial stability of the dose for an acceptable period, within which it can be read out. A novel method has been proposed to achieve this aim by incorporation of an anti-oxidant in the present Fricke gel dosimeter. The modified gel prepared in this study consisted of 50 mM sulfuric acid, 0.05 mM xylenol orange, 0.5 mM ferrous ammonium sulfate, and an optimal concentration of anti-oxidant. Different concentrations of the anti-oxidant (ascorbic acid and glycine) based gel dosimeters were prepared. The performance evaluations of the same were characterized dosimetrically with high energy photons (x- and gamma rays). Spectrophotometric measurements of gel dosimeters were performed at a wavelength of 585 nm and the post-irradiation diffusion was studied by observing the dose response over time. The spatial dose information from the large volume cylindrical gel phantoms was acquired using an in-house optical computed tomography scanner. Auto-oxidation and diffusion were controlled in the enhanced Fricke gel dosimeter by the incorporation of glycine as anti-oxidant. The post-irradiation dose in the gel dosimeter was stable up to 6 hours, thereby enhancing the longevity of three-dimensional (3D) dose. The widely established limitations of Fricke gel dosimeter viz., auto-oxidation and diffusion were overcome using a novel method that incorporated optimal quantity of glycine as a suitable anti-oxidant. This modified Fricke gel dosimeter could be used as an effective 3D dosimeter for practical applications in radiotherapy.


Aneurysm recurrence associated with induced hypertension and hypervolemia.
A case of angiographic recurrence of a previously clipped large distal basilar aneurysm associated with prolonged hypervolemic and hypertensive therapy for vasospasm is reported. Currently, the most effective therapy for reversing neurological deficits secondary to vasospasm and for augmenting cerebral blood flow is induced hypertension and hypervolemia. The complication of aneurysm enlargement with this therapeutic modality has been postulated but not previously demonstrated.


Expressions of uncertainty in invisible scientific and religious phenomena during naturalistic conversation.
Across cultures, studies report more confidence in the existence of unobservable scientific phenomena, such as germs, as compared to unobservable religious phenomena, such as angels. We investigated a potential cultural mechanism for the transmission of confidence in the existence of invisible entities. Specifically, we asked whether parents in societies with markedly different religious profiles-Iran and China-signal differential confidence across the domains of science and religion during unmoderated conversations with their children (N = 120 parent-child dyads in total; 5- to 11-year-olds). The results revealed that parents used fewer lexical cues to uncertainty when discussing scientific phenomena, as compared to religious phenomena. Unsurprisingly, this cross-domain distinction was observed among majority belief, secular parents in China (Study 2). More importantly, however, the same pattern was observed among parents in Iran, a highly religious society (Study 1), as well as among minority belief, religious parents in China (Study 2). Thus, adults in markedly different belief communities spontaneously express less confidence in religious, as compared to scientific, invisible entities in naturalistic conversation. These findings contribute to theories on the role of culture and testimony in the development of beliefs about unobservable phenomena.


Enhancing damage visibility on metallic bearing surfaces: a simple technique for photography and viewing.
Damage to metallic bearing surfaces typically involves scratches, scrapes, metal transfer, and organic deposits. This damage can cause accelerated wear of the opposing surface and subsequent implant failure. Photography and viewing of metallic bearing surfaces, for documenting this damage, are hindered by optical reflectivity. This note demonstrates a simple, practical technique for metallic bearing surface photography and viewing that minimizes this reflectivity problem, that does not involve any modification of the bearing surface, and that allows for improved observation and documentation of overall damage. When the metallic bearing surface is placed within a tube of translucent material, the appearance of damage on that bearing surface is dramatically enhanced, showing up against a smooth, even background with excellent contrast and with fine detail achievable.


Effects of jet nebulization on ventilator performance with different invasive ventilation modes: A bench study.
The effects of jet nebulization on ventilator performance in the volume control mode (VC) and pressure control mode (PC) of ventilation have not been determined. The present study investigated the impact of jet nebulization on ventilator performance in different modes in vitro. Two types of jet nebulizer (ventilator-integrated jet nebulizers, external jet nebulizer) and six types of ventilator were connected with a simulated lung to simulate aerosol therapy during mechanical ventilation. The ventilation modes were set to VC and PC, and the driving flows of external jet nebulizer were set at 4 L/min and 8 L/min, respectively. Jet nebulizers were placed between patient airway and Y-piece or at 15 cm from the Y-piece in the inspiratory limb. The effects of jet nebulization were compared with the baseline of triggering performance, control performance, and tidal volume under different experimental conditions. Ventilator-integrated jet nebulizers had no effect on ventilator performance in different modes (all P > 0.05). However, the effects of external jet nebulizers on ventilator performance varied widely: for triggering performance, all parameters were increased in different modes and nebulization positions (all P < 0.05), including the time from the beginning of the inspiratory effort to the lowest value of airway pressure needed to trigger the ventilator (TPmin), the time to trigger (Ttrig), and the magnitude of airway pressure drop needed to trigger (Ptrig); for control performance, peak inspiratory pressure (Ppeak) and peak inspiratory flow(Pflow) were increased in the VC mode (P < 0.05), but not significantly changed in the PC mode (P > 0.05);the actual tidal volume (VT) and expiratory tidal volume monitored (VTe) were significantly increased (P < 0.05), however, the inspiratory tidal volume monitored (VTi) was not affected by jet nebulization in the VC mode. In the PC mode, there were no significant changes in VT, whereas VTi decreased and VTe increased (P < 0.05). The higher the driving flow of external jet nebulizers, the stronger the impact on ventilator performance (all P < 0.05). Triggering performance was decreased in both the VC and PC modes when using an external jet nebulizer, while the effects of nebulization on control performance and tidal volume varied significantly.


[Bilateral amyotrophic neuralgia (Parsonage Turner syndrome) with HIV seroconversion].
We report a unusual case of neuralgic amyotrophy (NA) occurring during the seroconversion stage of an HIV infection. Combined with previously published cases, our observation suggests that NA associated with HIV could belong to the group of early multiplex mononeuritis. Neurologists should be aware of HIV infection when managing a patient with NA.


Mixed logistic regression in genome-wide association studies.
Mixed linear models (MLM) have been widely used to account for population structure in case-control genome-wide association studies, the status being analyzed as a quantitative phenotype. Chen et al. proved in 2016 that this method is inappropriate in some situations and proposed GMMAT, a score test for the mixed logistic regression (MLR). However, this test does not produces an estimation of the variants' effects. We propose two computationally efficient methods to estimate the variants' effects. Their properties and those of other methods (MLM, logistic regression) are evaluated using both simulated and real genomic data from a recent GWAS in two geographically close population in West Africa. We show that, when the disease prevalence differs between population strata, MLM is inappropriate to analyze binary traits. MLR performs the best in all circumstances. The variants' effects are well evaluated by our methods, with a moderate bias when the effect sizes are large. Additionally, we propose a stratified QQ-plot, enhancing the diagnosis of p values inflation or deflation when population strata are not clearly identified in the sample. The two proposed methods are implemented in the R package milorGWAS available on the CRAN. Both methods scale up to at least 10,000 individuals. The same computational strategies could be applied to other models (e.g. mixed Cox model for survival analysis).


A note concerning the effect of a kinesthetic memory load on the retention of movement end-location.
Remembering the distance or end-location of an interpolated movement interfered equally with the retention of criterion movement end-location. Interpolated distances were recalled less well than interpolated locations. These results were interpreted as evidence of capacity interference rather than structural interference with a visual/kinesthetic integrated store.


Evidence of apothecial ancestry in the cleistothecial ascomata of Pleuroascus nicholsonii.
Ascomata of Pleuroascus nicholsonii, a rarely reported cleistothecial ascomycete, show little overt evidence of a putative affiliation with the Leotiomycetes. However, close examination of the plectomycetous centrum reveals a distorted hymenium arising from a system of branched ascogenous hyphae, and twisted or coiled uniseriate ascospores enclosed within what appears to be the remains of the spore investing membrane of a clavate ascus precursor. Abundant sterile elements arising from the inner wall layer of the peridium and interspersed throughout the centrum are interpreted as representing vestiges of apically branched paraphyses. Whole ascomata show limited signs of polarity, although the characteristic, tightly coiled appendages generally arise along or below the equatorial region and there is a marked thinning of subicular hyphae over the crown of the cleistothecium. The mature peridium, which consists of a thin, melanized outer layer of squamulose cells, splits irregularly along intercellular grooves when disturbed. The adaptive significance of these characteristics is unknown, but the persistent paraphyses, the easily fractured and darkly pigmented membranous peridium, an ascospore mass that is dry at maturity, and the tendency for ascomata to cling together in clumps can be rationalized in the context of a coprophilous life-style. Collection data for P. nicholsonii provide further support for this supposition because five of the six reported specimens are from rodent dung.


Design, synthesis and biological evaluation of novel chalcone-like compounds as potent and reversible pancreatic lipase inhibitors.
Pancreatic lipase (PL), a crucial enzyme responsible for hydrolysis of dietary lipids, has been validated as a key therapeutic target to prevent and treat obesity-associated metabolic disorders. Herein, we report the design, synthesis and biological evaluation of a series of chalcone-like compounds as potent and reversible PL inhibitors. Following two rounds of structural modifications at both A and B rings of a chalcone-like skeleton, structure-PL inhibition relationships of the chalcone-like compounds were studied, while the key substituents that would be beneficial for PL inhibition were revealed. Among all tested chalcone-like compounds, compound B13 (a novel chalcone-like compound bearing two long carbon chains) displayed the most potent PL inhibition activity, with an IC50 value of 0.33 μM. Inhibition kinetic analyses demonstrated that B13 could potently inhibit PL-mediated 4-MUO hydrolysis in a mixed inhibition manner, with the Ki value of 0.12 μM. Molecular docking simulations suggested that B13 could tightly bind on PL at both the catalytic site and a non-catalytic site that was located on the surface of PL, which was consistent with the mixed inhibition mode of this agent. In addition, B13 displayed excellent stability in artificial gastrointestinal fluids and good metabolic stability in human liver preparations. Collectively, our findings suggested that chalcone-like compounds were good choices for design and development of orally administrated PL inhibitors, while B13 could be served as a promising lead compound to develop novel anti-obesity agents via targeting on PL.


Extractionless high-performance liquid chromatographic method for the determination of diclofenac in human plasma and urine.
An assay using reversed-phase high-performance liquid chromatography with ultraviolet detection, at 278 nm, was developed to measure diclofenac in human plasma and urine at concentrations suitable for biopharmaceutical studies. Indomethacin was used as internal standard and separation was performed at 40 degrees C on a C18 Spherisorb column with acetonitrile-0.1 M sodium acetate (35:65, v/v) (pH 6.3) as mobile phase. The sample preparation is simple and rapid (extractionless), and the total run time is less than 5 min. The retention time is 2.8 min for diclofenac and 3.6 min for indomethacin. The detection limit is 0.2 microgram/ml using a 20-microliters loop.


Isolated tarso-conjunctival superior eyelid traumatic laceration.
To report a unusual case of an isolated traumatic stellated tarso-conjunctival laceration located in the upper left eyelid without eyelid margin involvement and with normal ocular examination. A 19 year-old male wounded by a bokken (wooden katana) while practicing a sham duel had an isolated eyelid tarso-conjunctival laceration, without any other eyelid layer damage, neither skin nor muscle. Treatment was conservative without suture, by means of compressive occlusion fixing the pieces of broken tarsus in the correct position. The aim of the treatment was to avoid any wrong eyelid position secondary to healing. The eyelid maintained normal structure and movement in the follow-up at 8 months. Tarsal plate rupture is usually combined with other eyelid layer damage, which usually requires suture by layers. If eyelid skin and muscle are intact, we may choose conservative management.


Real-time monitoring of endogenous noradrenaline release in rat brain slices using fast cyclic voltammetry: 3. Selective detection of noradrenaline efflux in the locus coeruleus.
Fast cyclic voltammetry (FCV) at carbon fibre microelectrodes was used to monitor 'real time' endogenous noradrenaline (NA) efflux in superfused slices of rat locus coeruleus (LC) following local electrical stimulation. When stimulated with a standard train (30 pulses, 100 Hz, 0.2 ms, 10 mA, every 5 min), efflux of monoamine was constant over the experimental period (2.5 h): Amine efflux declined by only 16 +/- 5% while uptake half-life lengthened by only 9 +/- 8%. When calibrated in solutions of NA, peak amine efflux corresponded to 0.31 +/- 0.04 microM (mean +/- S.E.M., n = 28) and was removed by uptake with a half-life of 2.93 +/- 0.28 s (n = 16). The released compound was confirmed as NA on the basis of pharmacological and electrochemical criteria. Stimulated monoamine efflux was reversibly reduced by 78% by omission of Ca2+ from the superfusate for 30 min (P < 0.05). Ro 4-1284 (1 microM), a fast-acting reserpine-like drug, decreased amine efflux by 86% (P < 0.05). The monoamine oxidase inhibitor pargyline (2 microM) increased efflux by 30% (P < 0.05). Desipramine (0.05 microM), a selective NA uptake blocker, significantly increased amine efflux (by 96%, P < 0.05) and uptake half-life (by 314%, P < 0.05). Fluvoxamine (0.5 microM), the selective serotonin (5HT) uptake blocker, increased efflux by 59% (P < 0.05) and the uptake half-life by 122% (P < 0.05). Vanoxerine (GBR 12909: 0.3 microM), the dopamine (DA) uptake blocker, had no effect on amine efflux or uptake half-life. The voltammogram of the released amine had single oxidation and reduction peaks.(ABSTRACT TRUNCATED AT 250 WORDS)


Structural alterations of the RB1 gene in human soft tissue tumours.
Sixty-nine primary soft tissue tumours were examined for alterations of the RB1 gene which has previously been implicated in the genesis of retinoblastoma. In three tumours loss of both alleles of this gene (homozygous deletion) was detected. Two of these, both leiomyosarcomas, contained a chromosomal breakpoint within the RB1 gene, while in the third tumour, a radiation induced sarcoma, complete deletion was observed. Using a probe that detects a polymorphic locus within the RB1 gene we found loss of only one allele (heterozygous deletion) in 33% of soft tissue sarcomas examined, including two leiomyosarcomas, a malignant peripheral nerve sheath tumour, a rhabdomyosarcoma and a chondrosarcoma. When taken together our results suggest that alterations of the RB1 locus may play an important part in the pathogenesis of soft tissue tumours and particularly in leiomyosarcomas which accounted for four of the eight RB1 alterations observed in this study.


Prosthetic valve dysfunction presenting as intermittent acute aortic regurgitation.
We describe the case of a 43 year old man with a history of aortic stenosis, for which he had undergone aortic valve replacement in 1991 with a 25-mm Medtronic Hall prosthesis. He presented with several acute episodes of dyspnea and flash pulmonary edema. Transthoracic and transesophageal echocardiography performed to evaluate prosthetic valve function revealed evidence of "intermittent" episodes of AI, documented on color M-mode flow mapping to have a variable duration of diastolic flow (early vs. pandiastolic) across the left ventricular outflow tract and the pulse wave Doppler in the descending thoracic aorta showed similar variability in the duration of diastolic flow reversal.


Genetic Counselors' Experiences Regarding Communication of Reproductive Risks with Autosomal Recessive Conditions found on Cancer Panels.
The development of hereditary cancer genetic testing panels has altered genetic counseling practice. Mutations within certain genes on cancer panels pose not only a cancer risk, but also a reproductive risk for autosomal recessive conditions such as Fanconi anemia, constitutional mismatch repair deficiency syndrome, and ataxia telangiectasia. This study aimed to determine if genetic counselors discuss reproductive risks for autosomal recessive conditions associated with genes included on cancer panels, and if so, under what circumstances these risks are discussed. An on-line survey was emailed through the NSGC list-serv. The survey assessed 189 cancer genetic counselors' experiences discussing reproductive risks with patients at risk to carry a mutation or variant of uncertain significance (VUS) in a gene associated with both an autosomal dominant cancer risk and an autosomal recessive syndrome. Over half (n = 82, 55 %) reported having discussed reproductive risks; the remainder (n = 66, 45 %) had not. Genetic counselors who reported discussing reproductive risks primarily did so when patients had a positive result and were of reproductive age. Reasons for not discussing these risks included when a patient had completed childbearing or when a VUS was identified. Most counselors discussed reproductive risk after obtaining results and not during the informed consent process. There is inconsistency as to if and when the discussion of reproductive risks is taking place. The wide variation in responses suggests a need to develop professional guidelines for when and how discussions of reproductive risk for autosomal recessive conditions identified through cancer panels should occur with patients.


Metabolic effects of proglycosyn.
Proglycosyn, a phenylacyl imidazolium compound that lowers blood glucose levels, was demonstrated previously to promote hepatic glycogen synthesis, stabilize hepatic glycogen stores, activate glycogen synthase, inactivate glycogen phosphorylase, and inhibit glycolysis. In the present study proglycosyn was found to inhibit fatty acid synthesis, stimulate fatty acid oxidation, and lower fructose 2,6-bisphosphate levels, but to have no significant effects on cell swelling and the levels of cAMP in hepatocytes prepared from fed rats. Verapamil and atropine blocked the effects of proglycosyn on glycogen metabolism, but these compounds inhibit proglycosyn accumulation by hepatocytes. Proglycosyn stimulated phosphoprotein phosphatase activity in postmitochondrial extracts, as measured by dephosphorylation of phosphorylase a and glycogen synthase D, but this action required a very high concentration of the compound, making it unlikely to be the actual mechanism involved. It is proposed that a metabolite of proglycosyn is responsible for its metabolic effects.


The implications of an incidental chronic lymphocytic leukaemia in a resection specimen for colorectal adenocarcinoma.
Colorectal cancer and B cell chronic lymphocytic leukaemia (CLL) have a significant incidence, which are increasing with the aging population. Evidence has been presented in the literature to suggest that the synchronous presentation of colorectal cancer and B cell CLL may be more than simply coincidental for these two common malignancies. We report an unusual case of a presumed B cell CLL diagnosed on the basis of histological analysis of lymph nodes recovered from a resection specimen for rectal adenocarcinoma. We considered aetiological factors which may have linked the synchronous diagnosis of the two malignancies and the potential implications for the natural history of the two malignancies on one another. A 70-year-old male underwent low anterior resection with total mesorectal excision for a rectal adenocarcinoma. His co-morbid conditions were chronic obstructive airways disease and ischaemic heart disease. General examination revealed no lymphadenopathy. Full blood count, urea and electrolytes and liver function tests were all within normal limits. As well as confirming a pT3 N1 adenocarcinoma, histological analysis showed lymph nodes with an infiltrate of small lymphoid cells. Immunohistochemical studies showed these cells to be in keeping with B cell CLL. Whilst unable to identify any common aetiological factors in the two malignancies in our patient, immunosuppression and genetic abnormalities have been identified as possible bases for an observed epidemiological association between colorectal cancer and haematological malignancies. Examples such as our case of synchronous diagnosis of two malignancies in a patient are likely to increase with the aging population. The potential affects of one malignancy on the natural history of the other warrants further study. In our case, we considered that slow progression of the B cell CLL may increase the risk of recurrent rectal adenocarcinoma.


Effect of neurotensin on glucose and insulin portal blood levels in hyperglycemic rats.
A new multiple sampling technique for obtaining blood from the portal vein has been used to investigate the effects of neurotensin on insulin and glucose portal blood levels in rats rendered hyperglycemic by a constant glucose infusion. The peptide has been first injected acutely (2 microgram/rat iv), and then constantly infused (0.5 microgram/min for 55 min). The preliminary results indicate that no effect of the acute injection could be observed, but hyperglycemia and hyperinsulinemia were induced by the constant infusion of the peptide. It is suggested that neurotensin may stimulate the release of insulin probably through a direct mechanism.


Association of malnutrition with SARS-CoV-2 vaccine response in patients undergoing hemodialysis.
Patients undergoing dialysis are less likely to develop immune responses to SARS-CoV-2 vaccine. Malnutrition is common in the dialysis population. However, whether malnutrition contributes to the impaired immunogenicity remains unknown. The aim of this study was to assess the association between nutritional status and SARS-CoV-2 vaccine response in patients receiving maintenance hemodialysis. A total of 206 hemodialysis patients (mean age, 67 ± 13 years) without prior SARS-CoV-2 infection were examined for the primary outcome of seroconversion, defined as the detection of IgG antibodies (≥50 AU/mL) to the receptor-binding domain of the S1 spike protein of SARS-CoV-2 one month after a priming dose of ChAdOx1 nCoV-19, an adenovirus-vectored vaccine. Nutritional status was assessed by using the Controlling Nutritional Status (CONUT) score, an objective indicator of nutrition incorporating serum albumin, total cholesterol, and total lymphocyte count, as well as the subjective global assessment (SGA). Overall, 16.5% of patients were classified as malnourished, and 64.1% of patients were at risk for malnutrition based on the CONUT score. Anti-SARS-CoV-2 IgG were the highest in patients with normal nutrition. In multivariate logistic regression analyses adjusted for age, sex, comorbidities, and use of immunosuppressants, patients with malnutrition remained less likely to develop an antibody response than those with normal nutrition (odds ratio 0.23, 95% CI, 0.07-0.76). SGA was a significant predictor of anti-SARS-CoV-2 IgG seroconversion in univariate but not multivariate analyses. Malnutrition according to CONUT score is associated with impaired humoral responses to SARS-CoV-2 vaccination in patients undergoing hemodialysis. Our results highlight the importance of incorporating nutritional assessment into routine dialysis care to identify patients at risk for suboptimal immune responses after SARS-CoV-2 vaccination. Further research is needed to determine whether nutritional intervention can improve immune responses in these vulnerable patients.


Intravascular papillary endothelial hyperplasia on the penis: report of a case.
An 82-year-old Japanese man with intravascular papillary endothelial hyperplasia on the penis is described. To the best of our knowledge, this is the first report of a patient who developed this tumor on his penis.


Developmental momentum toward substance dependence: natural histories and pliability of risk factors in youth experiencing chronic stress.
Mitigation of substance use (SU) disorder (SUD) risk factors is a common goal of prevention. Research has clarified much about risk factors including their prediction of SU/SUD, associations with other etiological variables and mediation of SU outcomes. Greater understanding of the emergence of risk factors themselves may improve prevention. For example, in lieu of experimental data, the level of resistance to change of a risk factor (its pliability) could inform "dosage" of intervention needed to reduce the risk. Two attributes of 22 previously-documented predictors of SU/SUD were quantified: natural history (average age-related trend) and pliability (quantified using correlations between intercepts and growth parameters of hierarchical linear modeling trajectories). The longitudinal sample of 1147 8- through 16-year-olds were recruited from a northeastern summer camp for youth experiencing chronic stress due to one or more stressors (X¯=2.2stressors, SD=1.41) which typically last at least one year. Half were male, 69.3% were European-American, 8.5% were African-American, and the remaining were small proportions each of other or mixed races/ethnicities. Average trajectories of 21 predictors correspond to increasing SUD risk with age. Predictor pliability varied greatly, ranging from extremely high for School Commitment to extremely low for Peer Pressure Susceptibility. Results suggest different intervention strategies may be needed to manage risk factors over the long-term. To illustrate, maintaining a high school commitment appears to require boosters whereas reducing peer pressure susceptibility appears to require high initial "dosage" with less need for boosters.


Segmental reflex inputs to motoneurons innervating dorsal neck musculature in the cat.
The responses to stimulation of upper cervical muscle and cutaneous afferents were studied in motoneurons innervating splenius, complexus, and biventer cervicis dorsal neck muscles of cats. Motoneurons innervating complexus and biventer cervicis fibers, which are in the deeper, longitudinally oriented muscles, were monosynaptically excited by ipsilateral Group I afferents from each of these muscles, but they did not receive significant input from splenius Group I afferents. Likewise, splenius motoneurons were not monosynaptically excited by ipsilateral afferents from complexus anf biventer cervicis. Stimulation of ipsilateral cutaneous afferents produced predominant excitation in splenius motoneurons, predominant inhibition in biventer cervicis motoneurons, and inhibition or mixed responses in complexus motoneurons. None of the neck motoneurons studied showed postsynaptic potentials following single or multiple shock stimulation of contralateral muscle nerves at stimulus intensities expected to excite exclusively Group I afferents. Higher intensity stimulation of contralateral muscle afferents, as well as fibers in the greater auricular nerves, produced predominant inhibition in all three neck motoneuron pools. Segmentally-excited afferents to neck motoneurons, like those from supraspinal systems, appear to evoke different patterns of synaptic responses in splenius motoneurons than they do in motoneurons innervating fibers in the deeper, longitudinally oriented complexus and biventer cervicis muscles.


The effects of patient education in COPD in a 1-year follow-up randomised, controlled trial.
The aims were to explore the effects and health economic consequences of patient education in patients with COPD in a 12-month follow-up. Sixty-two patients with mild to moderate Chronic Obstructive Pulmonary Disease (COPD) were at our out-patient clinic randomly allocated to an intervention group or a control group. The intervention group participated in a 4h group patient education, followed by one to two individual nurse- and physiotherapist-sessions. Self-management was emphasised following a stepwise treatment plan. Effectiveness was expressed in terms of number of general practitioner (GP) consultations, proportions in need of GP consultations, utilisation of rescue medication and patient satisfaction. Costs related to doctor visits, days off work, dispensed pharmaceuticals, hospital admissions, travel costs, educational and time costs were recorded. Patient education reduced the need for GP visits with 85% (from 3.4 to 0.5, P<0.001) and kept a greater proportion independent of their GP during the 12-month follow-up, compared with no education (73% versus 15%, respectively). Patient education reduced the need for reliever medication from 290 to 125 Defined Daily Dosages (DDD), and improved patient satisfaction with overall handling of their disease at GP. The control and intervention groups induced mean total costs of NOK 19,900 and 10,600 per patient, respectively. For every NOK put into patient education, there was a saving of 4.8. The Number Needed to Educate (NNE) to make one person satisfied with their GP was 4.5 and associated with a concomitant saving of NOK 41,900. Patient education of patients with COPD improved patient outcomes and reduced costs in a 12-month follow-up.


Environmental stress, ageing and glial cell senescence: a novel mechanistic link to Parkinson's disease?
Exposure to environmental toxins is associated with a variety of age-related diseases including cancer and neurodegeneration. For example, in Parkinson's disease (PD), chronic environmental exposure to certain toxins has been linked to the age-related development of neuropathology. Neuronal damage is believed to involve the induction of neuroinflammatory events as a consequence of glial cell activation. Cellular senescence is a potent anti-cancer mechanism that occurs in a number of proliferative cell types and causes the arrest of proliferation of cells at risk of malignant transformation following exposure to potentially oncogenic stimuli. With age, senescent cells accumulate and express a senescence-associated secretory phenotype (SASP; that is the robust secretion of many inflammatory cytokines, growth factors and proteases). Whereas cell senescence in peripheral tissues has been causally linked to a number of age-related pathologies, little is known about the induction of cellular senescence and the SASP in the brain. On the basis of recently reported findings, we propose that environmental stressors associated with PD may act in part by eliciting senescence and the SASP within non neuronal glial cells in the ageing brain, thus contributing to the characteristic decline in neuronal integrity that occurs in this disorder.


The use of the Minimum Data Set. Home Care in a case management project in Hong Kong.
130 hospital-discharged elderly patients received our comprehensive assessment by using a Chinese Minimum Data Set-Home Care (MDS-HC). Our case manager developed and implemented care plans with reference to the computer-generated Clients Assessment Protocols. Results showed that the MDS-HC was sensitive to identify elderly persons' holistic needs, and helpful in formulating all-inclusive care plans.


The relationships of a rationality/antiemotionality personality scale to mortalities of cancer and cardiovascular disease in a community population in Japan.
Grossarth-Maticek et al. reported that an individual's level on a rationality/antiemotionality (R/A) personality was strongly predictive of cancer, ischemic heart disease and stroke mortality. To investigate the relationships of an individual's level on the R/A personality to cancer and cardiovascular disease mortality in Japan, we conducted a population-based cohort study. A self-administered questionnaire was distributed to 36990 Japanese residents in September 1992. The response rate was 90.3%. Data from 13226 males and 14880 females were analyzed. Dates and causes of death through December 31, 1999 were obtained for deceased participants. The results from multivariate hazard ratios (HRs) revealed that males scoring in the middle level compared to those scoring in the lower level of the R/A personality scale decreased their risk of death from cancer and cardiovascular diseases after controlling for covariates. The level on the R/A personality scale may affect mortality from cancer and cardiovascular diseases differently in Japan.


Safe handoff practices and improvement of communication in different paediatric settings.
Inadequate information management, especially during patient handoff, contributes to a large part of health care-related adverse events. The Committee for Quality of Care and Patient Safety of the Asociación Española de Pediatría has developed this document to provide an overview of handover practices in different paediatric care settings (emergency, inpatient, intensive care, neonatal and primary care). It describes resources to achieve safe and effective communication in all these settings, such as standardised handoff tools. It also proposes recommendations for the prevention of medication errors during the handover process, to improve safety in interhospital and intrahospital patient transfer, and to optimise communication and continuity of care in chronically ill and medically complex children.


The frequency gradient of human resting-state brain oscillations follows cortical hierarchies.
The human cortex is characterized by local morphological features such as cortical thickness, myelin content, and gene expression that change along the posterior-anterior axis. We investigated if some of these structural gradients are associated with a similar gradient in a prominent feature of brain activity - namely the frequency of oscillations. In resting-state MEG recordings from healthy participants (N = 187) using mixed effect models, we found that the dominant peak frequency in a brain area decreases significantly along the posterior-anterior axis following the global hierarchy from early sensory to higher order areas. This spatial gradient of peak frequency was significantly anticorrelated with that of cortical thickness, representing a proxy of the cortical hierarchical level. This result indicates that the dominant frequency changes systematically and globally along the spatial and hierarchical gradients and establishes a new structure-function relationship pertaining to brain oscillations as a core organization that may underlie hierarchical specialization in the brain.


The clinical and serological associations of hypocomplementemia in a longitudinal sle cohort.
In SLE, low complement is an important serological manifestation. Recent classification criteria include hypocomplementemia and one gives additional weight if both C3 and C4 are low. We evaluated patients with a history of, and those with persistently, low complement. As complement activation occurs in the antiphospholipid antibody syndrome, an analysis was also performed on those with positive antiphospholipid antibodies to evaluate thrombotic outcomes. In a longitudinal SLE cohort, organ manifestations, damage, C3, C4 and antiphospholipid antibodies were assessed quarterly. Using univariate and multivariate methods we compared those with and without a history of low C3, low C4 and both. We evaluated those who had a history of low complement at any time point, and those who had persistent hypocomplementemia. Further analysis considered thrombotic outcomes in patients with positive antiphospholipid antibodies and a history of low complement. 2399 patients were evaluated. Fifty-five percent had a history of low C3 and 47% low C4; 83 (4%) had persistently low C3 and 65 (3.2%) had persistently low C4. Hematological, renal and serological abnormalities associated with a history of low C3 but not low C4. With anticardiolipin antibodies, a history of hypocomplementemia (both C3 and C4 low) associated with stroke and deep venous thrombosis. Low C4 was a weak marker in terms of the associated clinical and serological manifestations. Low C3 associated with renal involvement and poor renal outcomes. A history of both low C3 and C4 associated with stroke in the presence of lupus anticoagulant or anticardiolipin antibodies, and low C4 with digital gangrene (with lupus anticoagulant).


Proposal for a simple and effective diagrammatic representation of root canal configuration for better communication amongst oral radiologists and clinicians.
Root canal anatomy has been proved to be a complex canal configuration system. The negotiation and cleaning of this system is essential for successful root canal treatment. The present root canal classification systems are unable to transfer the clinically relevant information about the canal system from the oral radiologist to the treating clinician. Thus, a simple and effective diagrammatic representation of the canal system, depicting the major canals, important changes during their course along with other relevant information has been presented. The proposed representation consists of five horizontal lines dividing the tooth into four segments from the point of reference to apical foramen. Each line has been designated with different line style. The diagrammatic images, one anterior and one posterior multi-rooted tooth, are given for easy understanding of the orientation of image. The whole image can be saved in portable network graphics format and can be imported to any word processing document. The image can be printed in the reporting sheet. Applying the same proposal, some of the diagrammatic representations have been showed. This proposal for diagrammatic representation of root canal configuration can be helpful in getting an approximate distribution of the canals in a relatively simple manner. This scheme also provides valuable clinical information about the root canal system, which the other classifications fail to represent.


[Hearing rehabilitation with the cochlea implant following translabyrinthine CPA tumor removal ?]
We present a quality analysis of 10 patients with an individual treatment trial for a simultaneous or consecutive cochlea implantation after translabyrinthine removal of a neurinoma at the cerebellopontine angle. The results show that most of the patients benefit from the cochlea implantation after unilateral deafness. Through a careful surgical preparation technique at the inner ear canal and its surroundings the morphological and functional integrity of the neurovascular structures can be guaranteed.


Experience of pharmacy involvement in a disaster simulation exercise within a pediatric hospital emergency department: A pilot project.
In this descriptive report, we describe a unique trial of pharmacist participation in a multidisciplinary pediatric emergency department disaster simulation exercise. With the number of disasters increasing worldwide, the role of pharmacists in disaster response is of particular interest to the profession. This observational study describes pharmacist participation in a disaster simulation exercise. An evaluation tool was developed to assess participants' performance in the following domains: communication, pharmacotherapy, problem solving/decision making, and teamwork/organization. The observers used a rating scale of "concise/prompt," "needs improvement," or "not done" to evaluate performance on each objective. The participants' self-perceived knowledge of disaster response was assessed with pre- and postsimulation surveys using Likert scales. Five simulation exercises were held from June to October 2019, with 2 pharmacists participating in each simulation. Within the problem solving/decision making and communication domains, pharmacists were concise/prompt 66% of the time, while they were concise/prompt for 88.8% and 92.5% of tasks in the teamwork/organization and pharmacotherapy domains, respectively. Surveys of self-perceived knowledge revealed that while only 10% of pharmacists felt "moderately prepared" prior to the simulation exercise, 80% of pharmacists felt moderately prepared to care for patients during a disaster event after the simulation exercise. This report describes a unique approach of including emergency department-trained pharmacists in disaster simulation exercises to enhance their professional development, improve team dynamics in a mass casualty scenario, and increase their own reported level of preparedness to effectively manage a surge in critically ill pediatric patients.


A mixed methods evaluation of the acceptability of therapy using LEGO® bricks (LEGO® based therapy) in mainstream primary and secondary education.
Many autistic children and young people need extra support with social skills. Social skills programmes, such as LEGO® based therapy (LBT), are commonly used to help with these difficulties. The aim of this study was to examine the acceptability of LBT using qualitative interviews and questionnaires with facilitators and parents/guardians on behalf of autistic children and young people. Acceptability was measured in line with constructs of the Theoretical Framework of Acceptability. Questionnaires were analyzed descriptively and between group comparisons were undertaken using the Mann-Whitney U Test. Telephone interviews were undertaken with a sub-sample of facilitators. All interviews were recorded, transcribed verbatim, and framework analysis was performed by two researchers supported by NVivo. The questionnaire response rate was 80% for facilitators and 77% for parents/guardians. Overall acceptability, measured on a 1-5 (minimum-maximum) scale, was high for both facilitators and parents/guardians with a median (range) of 5 (4-5) and 4 (3-5), respectively. Facilitators rated the acceptability of the programme significantly higher overall than parents (p < 0.001). Facilitators reported that participants and wider school staff viewed the programme positively. They observed improvements in communication and social skills during the sessions. Potential barriers to programme delivery, such as resources and staff schedules, were identified but facilitators reported that these challenges did not outweigh the benefits. There is increasing emphasis on the role of schools in seeking to improve social outcomes for autistic children therefore this high degree of acceptability makes this an attractive school-based programme for schools, autistic children and their families. LAY SUMMARY: Social skills programmes, such as LEGO® based therapy (LBT), are often used to help autistic children and young people with their social skills. The acceptability of LBT with school staff and parents/guardians on behalf of children and young people was explored using interviews and questionnaires. Our results show that LBT is viewed as a highly acceptable programme that can help autistic children and young people improve their communication and social skills.


Retinoic acid receptor-α regulates synthetic events in human platelets.
Essentials Platelets express retinoic acid receptor (RAR)α protein, specifically binding target mRNAs. mRNAs under RARα control include MAP1LC3B2, SLAIN2, and ANGPT1. All-trans retinoic acid (atRA) releases RARα from its target mRNA. RARα expressed in human platelets exerts translational control via direct mRNA binding. Background Translational control mechanisms in platelets are incompletely defined. Here, we determined whether the nuclear transcription factor RARα controls protein translational events in human platelets. Methods Isolated human platelets were treated with the pan-RAR agonist all-trans-retinoic acid (atRA). Global and targeted translational events were examined. Results Stimulation of platelets with atRA significantly increased global protein expression. RARα protein bound to a subset of platelet mRNAs, as measured by next-generation RNA-sequencing. In-depth analyses of 5' and 3'-untranslated regions of the RARα-bound mRNAs revealed consensus RARα binding sites in microtubule-associated protein 1 light chain 3 beta 2 (MAP1LC3B2), SLAIN motif-containing protein 2 (SLAIN2) and angiopoietin-1 (ANGPT1) transcripts. When platelets were treated with atRA, binding interactions between RARα protein and mRNA for MAP1LC3B2, SLAIN2 and ANGPT1 were significantly decreased. Consistent with the release of bound RARα protein from MAP1LCB2mRNA, we observed an increase in the synthesis of MAP1LC3B2 protein. Conclusions These findings provide the first evidence that RARα, a nuclear transcriptional factor, regulates synthetic events in anucleate human platelets. They also reveal an additional non-genomic role for RARα in platelets that may have implications for the vitamin A-dependent signaling in humans.


Differentially evolved drought stress indices determine the genetic variation of Brassica napus at seedling traits by genome-wide association mapping.
Drought seriously curtails growth, physiology and productivity in rapeseed (Brassica napus). Although drought tolerance is a complex trait, efficient phenotyping and genotyping has led to the identification of novel marker-trait associations underlying drought tolerance. A diverse panel of 228 Brassica accessions was phenotyped under normal (without stress) and water-stress conditions, simulated by polyethylene glycol (PEG-6000) (15% PEG stress) at the seedling stage; stress tolerance index (STI) and stress susceptibility index (SSI) values were acquired. Genome-wide association studies (GWAS) using 201 817 high quality SNPs identified 314 marker-trait associations strongly linked with drought indices and distributed across all nineteen chromosomes in both the A and C genomes. None of these quantitative trait loci (QTL) had been previously identified by other studies. We identified 85 genes underlying these QTL (most within 100 kb of associated SNPs) which were orthologous to Arabidopsis genes known to be associated with drought tolerance. Our study provides a novel resource for breeding drought-tolerant Brassica crops.


Impact of novel psychosocial programming on readmission and recidivism rates among patients with violence-related trauma.
The Victims of Crime Advocacy and Recovery Program (VOCARP) provides advocacy, mental health resources, and educational materials. This study will report complications, readmissions, and recidivism among crime victims, and who used or did not use victim services. Patients engaged with programming from 3/1/17 until 12/31/18 were included. Control groups were patients injured by violent trauma without VOCARP use (N = 212) and patients injured by unintentional injuries (N = 201). Readmissions, complications, reoperations, and trauma recidivism were reported. 1019 patients (83%) used VOCARP. VOCARP users were less often male (56% vs. 71%), less commonly married (12% vs. 41%), and had fewer gunshot wounds (GSWs, 26% vs. 37%) and sexual assaults (4.1% vs. 8%), all p < 0.05. Of all 1,423 patients, 6.6% had a readmission and 7.4% developed a complication. VOCARP patients had fewer complications (4.5% vs. 13.7%), infections (2% vs. 9%), wound healing problems (1% vs. 3.3%), and deep vein thromboses (0.3% vs. 1.9%), all p < 0.05, but no differences in unplanned operations (4.5%). GSW victims had the most complications, readmissions, and unplanned surgeries. Prior trauma recidivism was frequent among all groups, with crime victim patients having 40% prior violence-related injury (vs 9.0% control, p < 0.0001). Trauma recidivism following VOCARP use occurred in 8.5% (vs 5.7% for non-users, p = 0.16). Crime victims differ from other trauma patients, more often with younger age, single marital status, and unemployment at baseline. Complications were lower for VOCARP patients. GSW patients had the most complications, readmissions, and unplanned secondary procedures, representing a population for future attention.


A historical note about the sufficient cause model with special consideration of the work of Max Verworn 1912.
The aim of this paper is to present the historical roots of the sufficient component cause model, which is very well known in epidemiology. I have analyzed Max Verworn's writings on the description of the sufficient component cause model. Verworn introduced a precursor of the sufficient component cause model as early as 1912, possibly inspired by Ernst Mach. He argued for the abandonment of the concept of "cause" (singular). Instead, he preferred the term "conditions." Unlike Karl Pearson, Verworn was not opposed to causal considerations. However, according to Verworn, every process or state is determined by numerous conditions and not by a single factor or "cause." Instead of speaking of causalism, Verworn preferred to speak of conditionalism. The earliest description of the concept of the sufficient component cause model known in the epidemiological literature since 1976 dates back at least to 1912.


An Exo-Polygalacturonase Pgc4 Regulates Aerial Hyphal Growth and Virulence in Fusarium oxysporum f. sp. cubense race 4.
Fusarium oxysporum f. sp. cubense race 4 (Foc4) causes Fusarium wilt that affects banana plants, and hence, the molecular mechanisms of its virulence need to be investigated. We purified an exo-polygalacturonase (exo-PG), Pgc4, from Foc4. Pgc4 has an apparent molecular weight of 50.87 kDa based on sodium dodecyl sulphate-polyacrylamide gel electrophoresis. We further performed its sequence analysis and biochemical characterization. The two pgc4 genes encoding Pgc4 from Foc4 and Foc1 were 1434 bp in length and encoded 477 amino acids with differences, due to some nucleotide differences between the two. The Km and Vmax values of Pgc4 purified from Foc4 were determined to be 0.45 mg/mL and 105.26 Units·mg·protein-1 ·min-1, respectively. The recombinant proteins, r-Foc1-Pgc4 and r-Foc4-Pgc4, were expressed and purified from Pichia pastoris and showed optimal Pgc4 activity at 55 °C and pH 4.0; both could induce tissue maceration and necrosis in the "Guangfen-1" and "Baxi" varieties of banana but to a different extent. Phenotypic assays and complementation analyses revealed that, compared to the wild-type, the generated Foc4Δpgc4 mutant strain showed a lower aerial hyphal growth, grew slower, and had a reduced virulence. Therefore, our results demonstrate the function of Pgc4 as a pathogenicity factor of Foc4.


The making of India's COVID-19 disaster: A Disaster Risk Management (DRM) Assemblage analysis.
This article analyses the suite of policies and measures enacted by the Indian Union Government in response to the COVID-19 pandemic through apparatuses of disaster management. We focus on the period from the onset of the pandemic in early 2020, until mid-2021. This holistic review adopts a Disaster Risk Management (DRM) Assemblage conceptual approach to make sense of how the COVID-19 disaster was made possible and importantly how it was responded to, managed, exacerbated, and experienced as it continued to emerge. This approach is grounded in literature from critical disaster studies and geography. The analysis also draws on a wide range of other disciplines, ranging from epidemiology to anthropology and political science, as well as grey literature, newspaper reports, and official policy documents. The article is structured into three sections that investigate in turn and at different junctures the role of governmentality and disaster politics; scientific knowledge and expert advice, and socially and spatially differentiated disaster vulnerabilities in shaping the COVID-19 disaster in India. We put forward two main arguments on the basis of the literature reviewed. One is that both the impacts of the virus spread and the lockdown-responses to it affected already marginalised groups disproportionately. The other is that managing the COVID-19 pandemic through disaster management assemblage/apparatuses served to extend centralised executive authority in India. These two processes are demonstrated to be continuations of pre-pandemic trends. We conclude that evidence of a paradigm shift in India's approach to disaster management remains thin on the ground.


Clerodane diterpenoids from Dodonaea viscosa and their inhibitory effects on ATP citrate lyase.
Six undescribed clerodane diterpenoids, dodovisins A-F, together with nine known ones, were isolated from the aerial parts of Dodonaea viscosa (L.) Jacq. Their structures were elucidated by extensive spectroscopic techniques, X-ray crystallographic analysis, and ECD calculation. Dodovisins A and B possess a rare carbon skeleton featuring a bicyclo[6.2.0]decane motif. Dodovisins C-E represent the first clerodane diterpenoids with a 4(5 → 19)-abeo-2,4,10(1)-triene moiety. Dodovisins A, E, and strictic acid showed potent inhibitory activities against ATP citrate lyase.


Pilot testing HIV and intimate partner violence prevention modules among Spanish-speaking Latinas.
The purpose of this study was to test two modules of a theoretically based, gender- and culturally specific HIV intimate partner violence risk reduction intervention for Spanish-speaking Latinas. The themes of the modules were "Estás en una relación sana y segura?" (Are you in a healthy and safe relationship?) and "Mantenerse sana y segura" (Keeping yourself healthy and safe). An evaluative one-group, repeated measure design with measures collected at preintervention (N = 31), immediate postintervention (n = 26), and 1-month postintervention follow-up (n = 20) design was used to evaluate the intervention. Study results represent a small but significant first step toward an integrative approach to the prevention of two major and interrelated public health issues among an at-risk and underserved population.


Moderation Analysis of a couple-based HIV/STI Intervention Among Heterosexual Couples in the Criminal Legal System Experiencing Intimate Partner Violence: Results from a Randomized Controlled Trial.
Since the COVID-19 pandemic, intimate partner violence (IPV) rates have increased in the United States. Although accumulating research has documented the effectiveness of couple-based interventions in reducing HIV/STIs, it remains unclear whether they are effective and safe for couples experiencing IPV. We used moderation analysis from a randomized clinical trial to evaluate whether a couples-based HIV/STI intervention may have differential effectiveness in reducing HIV/STI risks among couples where one or both partners reported experiencing IPV compared to couples without such IPV among a sample of 230 men at risk for HIV/STIs who reported using drugs and were mandated to community supervision settings in New York City and their main female sexual partners. The findings of this study suggest that the effectiveness of this evidence-based couple HIV intervention in reducing condomless sex and other HIV/STI risks did not differ between couples with IPV compared to couples without IPV. Intimate partners who use drugs and are involved in the criminal legal system are disproportionately impacted by both HIV/STIs and IPV, underscoring the importance of couple-level interventions that may be scaled up to address the dyadic HIV risks and IPV together in community supervision settings.


Meniscal scaffolds: early experience and review of the literature.
Meniscal scaffold implants support the in-growth of new "meniscus like" tissue with the aim of alleviating post-meniscectomy knee pain and preventing further articular cartilage degeneration. Twenty-three patients underwent meniscal scaffold implantation (14 medial, 9 lateral) with either the Menaflex (ReGen Biologics) (n=12) or Actifit (Orteq) (n=11) scaffolds. Minimum follow-up was 1 year with a mean of 24.1 months (18-27) for the Menaflex and 14.7 months (12-18) for the Actifit groups. Mean age at surgery was 35 years (17-47) with a mean Outerbridge grade of 1.9 in the affected compartment. Eight (36%) underwent concurrent osteotomy, ligament reconstruction or microfracture of the tibial plateau. KOOS, Lysholm, Tegner activity and IKDC scores were collected pre-operatively and at six-month interval post-surgery. Assessment of the reconstruction was obtained with MRI scanning and arthroscopy. One scaffold tore and was revised at 19 months post-operatively. Twenty-one out of 23 (91.3%) had a significant improvement in knee scores when compared to pre-surgery levels at latest follow-up. Second-look arthroscopy in 14 at 1-year post-implantation showed variable amounts of regenerative tissue. There was no progression in chondral wear noted on repeat MRI scanning. Treatment with meniscal scaffold implants can provide good pain relief for the post-meniscectomy knee following partial meniscectomy. Longer follow-up is required to ascertain whether they also prevent the progressive chondral wear associated with a post-meniscectomy knee.


Carcinoembryonic antigen to detect hepatic metastases of colorectal cancers.
The spread of colorectal carcinoma (CRC) affects both staging and treatment. In this prospective study we examined the relationship between carcinoembryonic antigen (CEA) levels in bile, mesenteric venous blood, and peripheral venous blood, and the presence of occult hepatic metastases in patients with CRC. Sixty patients who underwent elective surgery at Ankara Oncology Hospital were voluntarily assigned to one of the three groups of 20 patients each. The control group consisted of patients operated on for benign biliary disorders, the second group consisted of patients with CRC without metastases, and the third group consisted of patients with CRC and isolated liver metastases. Bile, mesenteric venous blood, and peripheral venous blood was collected perioperatively for the measurement of CEA levels. The bile CEA levels were significantly higher in the CRC patients with metastases than in those without metastases and the controls. The CEA levels in the mesenteric venous blood and peripheral venous blood were significantly higher in the two groups of CRC patients than in the control group. Overt hepatic metastases later developed in seven patients from the CRC without metastases group who had relatively high CEA levels, but the difference was not significant. The CEA levels in bile, mesenteric venous blood, and peripheral venous blood were increased in patients with CRC and liver metastases. The detection of elevated CEA levels in bile taken at surgery did not herald metachronous hepatic metastases in CRC patients without liver metastases.


Maternal exposure to di-(2-ethylhexyl) phthalate disrupts placental growth and development in pregnant mice.
Di-(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and widely dispersed in the environment. DEHP exposure reduces embryo implantations, increases embryonic loss, and decreases fetal body weights. However, no detailed information is available about the effect of DEHP on the placentation during pregnancy. Thus, our aim was to explore the effect of DEHP on the growth and development of placenta in vivo. Mice were administered DEHP by gavages at 125, 250, 500 mg/kg/day from gestational days (GD) 1 until sacrifice. Results showed that DEHP treatment significantly reduced the weight of placenta at GD 13. Histopathologically, in DEHP-treated group, the ectoplacental cones significantly became smaller at GD9, and total area of placenta and area of spongiotrophoblast were significantly reduced at GD 13. Expression levels of Ascl2, Esx1 and Fosl1 mRNA dramatically decreased in DEHP-treated placenta at GD 13. DEHP administration disrupted labyrinth vascularization of placentas, and inhibited proliferation and induced apoptosis of placenta by the activation of caspase-3 and -8, up-regulation of Bax and down-regulation of Bcl-2 mRNA and protein at GD 13. In conclusion, these results suggest that adverse pregnancy outcomes including low birth-weight and pregnancy loss exposed to DEHP are possibly mediated, at least in part, via the suppression of placental growth and development.


Generation, establishment and characterization of a pluripotent stem cell line (CVTTHi001-A) from primary fibroblasts isolated from a patient with activated PI3 kinase delta syndrome (APDS2).
APDS2 is caused by mutations in PIK3R1 gene resulting in constitutive PI3Kδ activation. PI3Kδ is predominantly expressed in leukocytes and plays critical roles in regulating immune responses. Here we first derived fibroblast primary cells from a skin biopsy of a patient carrying a heterozygous single T deletion in intron 11 of the PIK3R1 gene. We next present the derivation of an induced pluripotent stem cell (iPS) line using a non-integrative reprogramming technology. Pluripotent-related hallmarks are further shown, including: iPSCs self-renewal and expression of pluripotent and differentiation markers after in vitro differentiation towards embryonic germ layers, assessed by RT-PCR and immunofluorescence.


WITHDRAWN: Quantitative analysis of solid binary mixtures-Vibrational spectroscopy of β-lactam antibiotics within THz-region.
This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


Evaluation of YouTube laparoscopic hysterectomy videos as educational materials during the COVID-19 era using the LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) and LAP-VEGaS video assessment tool.
With increasing numbers of laparoscopic hysterectomies, surgical trainees are compelled to learn more about endoscopy. Owing to coronavirus disease-related social distancing requirements, online education has gained prominence. Here, we aimed to investigate the laparoscopic hysterectomy video quality on YouTube using the LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS). YouTube was searched on June 7, 2020 using 'laparoscopic hysterectomy'. Three examiners evaluated videos using Global Operative Assessment of Laparoscopic Skills (GOALS). Subsequently, videos were assessed for their conformity to the LAP-VEGaS and LAP-VEGaS Video Assessment Tool. Interobserver reliability was estimated using intraclass coefficients and Cronbach's alpha. Cochran's Q test was used to determine correlations among quantitative data. The median GOALS score was 21.50. The observers' GOALS scores were significantly correlated. The results showed low conformity to the LAP-VEGaS. YouTube is the most used platform among trainees. The low YouTube video educational quality highlights the necessity for peer review, as trainees increasingly seek such resources during the pandemic.IMPACT STATEMENTWhat is already known on this subject? YouTube is the most commonly used online resource for educational material among surgical trainees. Online videos usually do not undergo a peer-review process. The LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) may be used to assess the educational quality of surgical videos.What do the results of this study add? To our knowledge, this is the first study on the quality of laparoscopic hysterectomy videos available on YouTube and the first study to evaluate YouTube laparoscopic surgery videos using the LAP-VEGaS Video Assessment Tool (VAT). Our study revealed the low educational quality of YouTube laparoscopic hysterectomy videos. The LAP-VEGaS VAT seems to be a valid and practical tool for assessing online laparoscopic hysterectomy videos.What are the implications of these findings for clinical practice and/or further research? Medical communities, especially tertiary care or academic centres, may upload educational peer-reviewed videos for trainees seeking this type of resource, especially during the coronavirus disease pandemic, as surgical education alternatives are limited.


Insulin therapy and blood glucose management in critically ill patients: a 1-day cross-sectional observational study in 69 French intensive care units.
Hyperglycaemia is common in critically ill patients, but blood glucose and insulin management may differ widely among intensive care units (ICUs). We aimed to describe insulin use practices and the resulting glycaemic control in French ICUs. We conducted a multicentre 1-day observational study on November 23, 2021, in 69 French ICUs. Adult patients hospitalized for an acute organ failure, severe infection or post-operative care were included. Data were recorded from midnight to 11:59 p.m. the day of the study by 4-h periods. Two ICUs declared to have no insulin protocol. There was a wide disparity in blood glucose targets between ICUs with 35 different target ranges recorded. In 893 included patients we collected 4823 blood glucose values whose distribution varied significantly across ICUs (P < 0.0001). We observed 1135 hyperglycaemias (> 1.8 g/L) in 402 (45.0%) patients, 35 hypoglycaemias (≤ 0.7 g/L) in 26 (2.9%) patients, and one instance of severe hypoglycaemia (≤ 0.4 g/L). Four hundred eight (45.7%) patients received either IV insulin (255 [62.5%]), subcutaneous (SC) insulin (126 [30.9%]), or both (27 [6.6%]). Among patients under protocolized intravenous (IV) insulin, 767/1681 (45.6%) of glycaemias were above the target range. Among patients receiving insulin, short- and long-acting SC insulin use were associated with higher counts of hyperglycaemias as assessed by multivariable negative binomial regression adjusted for the propensity to receive SC insulin: incidence rate ratio of 3.45 (95% confidence interval [CI] 2.97-4.00) (P < 0.0001) and 3.58 (95% CI 2.84-4.52) (P < 0.0001), respectively. Practices regarding blood glucose management varied widely among French ICUs. Administration of short or long-acting SC insulin was not unusual and associated with more frequent hyperglycaemia. The protocolized insulin algorithms used failed to prevent hyperglycaemic events.