3D printing for the integration of porous materials into miniaturised fluidic devices: A review.
Porous materials facilitate the efficient separation of chemicals and particulate matter by providing selectivity through structural and surface properties and are attractive as sorbent owing to their large surface area. This broad applicability of porous materials makes the integration of porous materials and microfluidic devices important in the development of more efficient, advanced separation platforms. Additive manufacturing approaches are fundamentally different to traditional manufacturing methods, providing unique opportunities in the fabrication of fluidic devices. The complementary 3D printing (3DP) methods are each accompanied by unique opportunities and limitations in terms of minimum channel size, scalability, functional integration and automation. This review focuses on the developments in the fabrication of 3DP miniaturised fluidic devices with integrated porous materials, focusing polymer-based methods including fused filament fabrication (FFF), inkjet 3D printing and digital light projection (DLP). The 3DP methods are compared based on resolution, scope for multimaterial printing and scalability for manufacturing. As opportunities for printing pores are limited by resolution, the focus is on approaches to incorporate materials with sub-micron pores to be used as membrane, sorbent or stationary phase in separation science using Post-Print, Print-Pause-Print and In-Print processes. Technical aspects analysing the efficiency of the fabrication process towards scalable manufacturing are combined with application aspects evaluating the separation and/or extraction performance. The review is concluded with an overview on achievements and opportunities for manufacturable 3D printed membrane/sorbent integrated fluidic devices.


Bullous and pustular rheumatoid vasculitis: treatment by plasma exchange.
A case of rheumatoid vasculitis (RV) with bullous and pustular lesions is reported. These skin manifestations represent very unusual symptoms of RV. A dramatic clinical improvement was obtained by plasma exchange and immunosuppressive therapy.


Association between frailty, delirium, and mortality in older critically ill patients: a binational registry study.
Frailty and delirium are prevalent among older adults admitted to the intensive care unit (ICU) and associated with adverse outcomes; however, their relationships have not been extensively explored. This study examined the association between frailty and mortality and length of hospital stay (LOS) in ICU patients, and whether the associations are mediated or modified by an episode of delirium. Retrospective analysis of data from the Australian New Zealand Intensive Care Society Adult Patient Database. A total of 149,320 patients aged 65 years or older admitted to 203 participating ICUs between 1 January 2017 and 31 December 2020 who had data for frailty and delirium were included in the analysis. A total of 41,719 (27.9%) older ICU patients were frail on admission, and 9,179 patients (6.1%) developed delirium during ICU admission. Frail patients had significantly higher odds of in-hospital mortality (OR: 2.15, 95% CI 2.05-2.25), episodes of delirium (OR: 1.86, 95% CI 1.77-1.95), and longer LOS (log-transformed mean difference (MD): 0.24, 95% CI 0.23-0.25). Acute delirium was associated with 32% increased odds of in-hospital mortality (OR: 1.32, 95% CI 1.23-1.43) and longer LOS (MD: 0.54, 95% CI 0.50-0.54). The odds ratios (95% CI) for in-hospital mortality were 1.37 (1.23-1.52), 2.14 (2.04-2.24) and 2.77 (2.51-3.05) for non-frail who developed delirium, frail without delirium, and frail and developed delirium during ICU admission, respectively. There was very small but statistically significant effect of frailty on in-hospital mortality (b for indirect effect: 0.00037, P < 0.001) and LOS (b for indirect effect: 0.019, P < 0.001) mediated through delirium. Both frailty and delirium independently increase the risk of in-hospital mortality and LOS. Acute delirium is more common in frail patients; however, it does not mediate or modify a clinically meaningful amount of the association between frailty and in-hospital mortality and LOS.


The Burden and Impact of Cough in Patients with Idiopathic Pulmonary Fibrosis: An Analysis of the Prospective Observational PROFILE Study.
Rationale: Cough is a commonly reported symptom in idiopathic pulmonary fibrosis (IPF) that negatively impacts patient-reported quality of life (QoL). However, both the burden of cough at diagnosis and the behavior of cough over time have not been systematically described in patients with IPF. Objectives: By utilizing data prospectively collected as part of the PROFILE study, we sought to assess cough burden and the impact that this has on QoL within a cohort of patients with newly diagnosed IPF. We also reexamined the previously described relationship between cough and mortality and the association of cough with the MUC5B promoter polymorphism. Methods: The PROFILE study is a multicenter, prospective, observational, longitudinal cohort study of incident IPF. Scores on the Leicester Cough Questionnaire (LCQ) were recorded at baseline in 632 subjects and then repeated 6 monthly in a subset (n = 216) of the cohort. Results: The median LCQ score at diagnosis was 16.1 (interquartile range, 6.5). LCQ scores remained stable over the subsequent year in the majority of patients. There was a weak association between LCQ score and baseline lung function, with worse cough-related QoL associated with more severe physiological impairment. Cough scores were not associated with subsequent mortality after correcting for baseline lung function. Furthermore, there was no relationship between LCQ score and MUC5B promoter polymorphism status. Conclusions: The burden of cough in IPF is high. Although cough is weakly associated with disease severity at baseline, cough-specific QoL, as measured by the LCQ, confers no prognostic value. Cough-specific QoL burden remains relatively stable over time and does not associate with MUC5B promoter polymorphism.


SMR (simulating medical reasoning): an expert shell for non-AI experts.
SMR is an expert system shell designed to put the tools for knowledge acquisition directly into the hands of the domain expert. Since the knowledge base is represented as free text within a simplified syntactic structure, it is intelligible to anyone familiar with medical terminology. The knowledge base includes the rules for inference making as well as data groupings and protocols to facilitate case recording. In this paper, SMR is presented from the expert's point of view, describing the rule syntax and procedures for formulating the required diagnostic or therapeutic knowledge in the chosen domain. Similarly, the end-user's application of the system to patient data and the provisions for exploring and explaining the system's conclusions and reasoning processes are detailed. Avoiding tedious and often inane dialog, the user enters all that is known about the patient and receives a report of the system's conclusions and recommendations followed by a list of observations to be made in patient follow-up. An expert system for evaluating the diabetic patient is used to illustrate system operations.


The combination of Alisma and Atractylodes ameliorates cerebral ischaemia/reperfusion injury by negatively regulating astrocyte-derived exosomal miR-200a-3p/141-3p by targeting SIRT1.
The combination of Alisma and Atractylodes (AA), a classical traditional Chinese herbal decoction, may protect against cerebral ischaemia/reperfusion injury (CIRI). However, the underlying mechanism has not been characterized. Intriguingly, exosomal microRNAs (miRNAs) have been recognized as vital factors in the pharmacology of Chinese herbal decoctions. The aim of the present study was to assess whether the neuroprotective effect of AA was dependent on the efficient transfer of miRNAs via exosomes in the brain. Bilateral common carotid artery ligation (BCAL) was used to induce transient global cerebral ischaemia/reperfusion (GCI/R) in C57BL/6 mice treated with/without AA. Neurological deficits were assessed with the modified neurological severity score (mNSS) and Morris water maze (MWM) test. Western blot (WB) analysis was used to detect the expression of sirtuin 1 (SIRT1) in the cerebral cortex. The inflammatory state was quantitatively evaluated by measuring the expression of phospho-Nuclear factor kappa B (p-NF-κB), Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) using WB analysis and glial fibrillary acidic protein (GFAP) immunohistochemical staining. The protein expression of zonula occluden-1 (ZO-1), occludin, caudin-5 and CD31 was examined by immunohistochemical staining to determine blood‒brain barrier (BBB) permeability. Exosomes were extracted from the brain interstitial space by ultracentrifugation and identified by transmission electron microscopy (TEM), WB analysis and nanoparticle tracking analysis (NTA). The origin of exosomes was clarified by measuring the specific mRNAs within exosomes via Real Time Quantitative PCR (RT‒qPCR). Differential miRNAs in exosomes were identified using microarray screening and were validated by RT‒qPCR. Exosomes were labelled with fluorescent dye (PKH26) and incubated with bEnd.3 cells, the supernatant was collected, IL-1β/TNF-α expression was measured using enzyme-linked immunosorbent assay (ELISA), total RNA was extracted, and miR-200a-3p/141-3p expression was examined by RT‒qPCR. In addition, the levels of miR-200a-3p/141-3p in oxygen glucose deprivation/reoxygenation (OGD/R)-induced bEnd.3 cells were quantified. The direct interaction between miR-200a-3p/141-3p and the SIRT1 3' untranslated region (3'UTR) was measured by determining SIRT1 expression in bEnd.3 cells transfected with the miR-200a-3p/141-3p mimic/inhibitor. Severe neurological deficits and memory loss caused by GCI/R in mice was markedly ameliorated by AA treatment, particularly in the AA medium-dose group. Moreover, AA-treated GCI/R-induced mice showed significant increases in SIRT1, ZO-1, occludin, caudin-5, and CD31 expression levels and decreases in p-NF-κB, IL-1β, TNF-α, and GFAP expression levels compared with those in untreated GCI/R-induced mice. Furthermore, we found that miR-200a-3p/141-3p was enriched in astrocyte-derived exosomes from GCI/R-induced mice and could be inhibited by treatment with a medium dose of AA. The exosomes mediated the transfer of miR-200a-3p/141-3p into bEnd.3 cells, promoted IL-1β and TNF-α release and downregulated the expression of SIRT1. No significant changes in the levels of miR-200a-3p/141-3p were observed in OGD/R-induced bEnd.3 cells. The miR-200a-3p/141-3p mimic/inhibitor decreased/increased SIRT1 expression in bEnd.3 cells, respectively. Our findings demonstrated that AA attenuated inflammation-mediated CIRI by inhibiting astrocyte-derived exosomal miR-200a-3p/141-3p by targeting the SIRT1 gene, which provided further evidence and identified a novel regulatory mechanism for the neuroprotective effects of AA.


Implementation of guidelines about women with previous cesarean section through educational/motivational interventions.
To investigate the effect of a quality improvement project with an educational/motivational intervention in northern Italy on the implementation of the trial of labor after cesarean section (CS). A pre-post study design was used. Every birth center (n = 23) of the Emilia-Romagna region was included. Gynecologist opinion leaders were first trained about Italian CS recommendations. Barriers to implementation were discussed and shared. Educational/motivational interventions were implemented. Data of multipara with previous CS, with a single, cephalic pregnancy at term, were collected during two periods, before (2012-2014) and after (2017-2019) the intervention (2015-2016). The primary outcome was the rate of vaginal birth after CS (VBAC) and perinatal outcomes. A total of 20 496 women were included. The VBAC rate increased from 18.1% to 23.1% after intervention (P < 0.001). The likelihood of VBAC-adjusted for age 40 years or older, Caucasian, body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) at least 30, previous vaginal delivery, and labor induction-was increased by the intervention by 42% (odds ratio 1.42, 95% confidence interval 1.31-1.54). Neonatal well-being was improved by intervention; neonates requiring resuscitation decreased from 2.1% to 1.6% (P = 0.001). Educating and motivating gynecologists toward the trial of labor after CS is worth pursuing. Health quality improvement is demonstrated by increased VBAC even improving neonatal well-being.


Caligid sea lice (Copepoda: Caligidae) from golden snapper Lutjanus johnii (Bloch) in Australian waters, with the recognition of Sinocaligus Shen, 1957 as a junior synonym of Caligus Müller, 1785.
Two species of sea lice are reported from the golden snapper Lutjanus johnii (Bloch) in Australian waters. One was represented by chalimus larvae, adult males and extremely slender females in which the genital complex is scarcely wider than the fourth pedigerous somite. These females are adult as they carry paired spermatophores and are identified as Caligus dussumieri Rangnekar, 1957 on the details of their appendages. Caligus dussumieri was formerly placed in the genus Sinocaligus Shen, 1957 but the characters supporting the validity of this genus are not robust, so it is here proposed to treat it as a junior subjective synonym of Caligus and transfer its species as: Caligus formicoides Redkar, Rangnekar & Murti, 1949, Caligus dussumieri Shen, 1957, Caligus caudatus (Gnanamuthu, 1950) new combination and Caligus timorensis (Izawa, 1995) new combination. All these species can be placed in the C. bonito-species group within Caligus. Caligus rivulatus Pilla, Vankara & Chikkam, 2012 is recognized as a junior subjective synonym of C. dussumieri. A new species, C. auriolus n. sp. is also described and this is placed in the C. diaphanus species-group. A key to species of this species-group is provided which indicates that C. auriolus n. sp. is most closely related to C. stromatei Krøyer, 1863 but the latter can be distinguished by the slender abdomen of the female and by the more complex myxal process on the maxilliped in the male.


The neural response to transcranial magnetic stimulation of the human motor cortex. II. Thalamocortical contributions.
Beta oscillations (15-30 Hz) constitute an important electrophysiological signal recorded in the resting state over the human precentral gyrus. The brain circuitry involved in generating the beta oscillations is not well understood but appears to involve both cortical and subcortical structures. We have shown that single pulses of transcranial magnetic stimulation (TMS) applied over the primary motor cortex consistently elicit a brief beta oscillation. Reducing the local cortical excitability using low-frequency repetitive TMS does not change the amplitude of the induced beta oscillation (Van Der Werf and Paus in Exp Brain Res DOI 10.1007/s00221-006-0551-2). Here, we investigated the possible involvement of the thalamus in the cortically expressed beta response to single-pulse TMS. We included eight patients with Parkinson's disease who had undergone unilateral surgical lesioning of the ventrolateral nucleus of the thalamus. We administered 50 single pulses of TMS, at an intensity of 120% of resting motor threshold, over the left and right primary motor cortex and, at the same time, recorded the electroencephalogram (EEG) using a 60-electrode cap. We were able to perform analyses on seven EEG data sets and found that stimulation of the unoperated hemisphere (with thalamus) resulted in higher amplitudes of the single-trial induced beta oscillations than in the operated hemisphere (with thalamotomy). The beta oscillation obtained in response to pulses applied over the unoperated hemisphere was also higher than that obtained in healthy controls. We suggest that (1) the beta oscillatory response to pulses of TMS applied over the primary motor cortex is higher in Parkinson's disease patients, (2) thalamotomy serves to reduce the abnormally high TMS-induced beta oscillations, and (3) the motor thalamus facilitates the cortically generated oscillation, through cortico-subcortico-cortical feedback loops.


A sequential trial of viloxazine (Vivalan) and imipramine in moderately depressed patients.
Patients with moderately severe depressive illness were matched for age, sex, severity of symptoms and number of previous episodes of affective illness. Eleven pairs of patients were randomly assigned to four weeks' treatment with either viloxazine (100 mg three times a day) or imipramine (50 mg three times a day). Both treatments were associated with significant reductions in the scores on depression rating scales. With a sequential testing plan based on repeated significance tests and formed into a skewed restricted plan, no difference in the two treatments was shown. Significantly fewer side effects were reported by patients receiving viloxazine.


Nucleus accumbens cholecystokinin (CCK) can either attenuate or potentiate amphetamine-induced locomotor activity: evidence for rostral-caudal differences in accumbens CCK function.
In this study the effects of cholecystokinin (CCK) microinjections into the rostral or caudal nucleus accumbens (Acc) on locomotor activation derived from systemic amphetamine treatment were examined. It was found that CCK microinjections into the rostral Acc attenuated and CCK microinjections into the caudal Acc potentiated amphetamine-induced locomotor activity. Results indicate that rostral Acc CCK microinjections have dopamine antagonistlike effects and caudal Acc CCK microinjections have dopamine agonistlike effects on amphetamine-induced locomotor activity. The relevance of the present findings to previous results regarding CCK-dopamine interactions is discussed.


Nanozymatic degradation and simultaneous colorimetric detection of tetracycline.
Tetracycline (TC) is a broad-spectrum antibiotic that can enter and accumulate in the human body via the food chain. Even in small concentrations, TC can cause several malignant health effects. We developed a system to simultaneously degrade the presence of TC in food matrices using titanium carbide MXene (FL-Ti3C2Tx). The FL-Ti3C2Tx exhibited biocatalytic property that activates hydrogen peroxide (H2O2) molecules in 3, 3', 5, 5'-tetramethylbenzidine (TMB environment. During the FL-Ti3C2Tx reaction, the catalytic products released turn the color of the H2O2/TMB system bluish-green. However, when TC is present, the bluish-green color does not appear. Via quadrupole time-of-flight mass spectrometry, we found that the TC is degraded by FL-Ti3C2Tx / H2O2 in preference to H2O2/TMB redox reaction, which intervenes in the color change. Hence, we developed a colorimetric assay to detect TC with a LOD of 615.38 nM and proposed two TC degradation pathways that facilitate the highly sensitive colorimetric bioassay.


Pregnancy outcomes following exposure to onabotulinumtoxinA.
To evaluate pregnancy outcomes following onabotulinumtoxinA (US Food and Drug Administration pregnancy category C product) exposure using the Allergan safety database. The Allergan Global Safety Database contains reports of onabotulinumtoxinA administration before/during pregnancy, including both prospective (reported before outcome) and retrospective (outcome already known) cases. The database was searched from 1/1/90 to 12/31/13 for eligible cases where treatment occurred during pregnancy or ≤3 months before conception. To minimize reporting bias, prevalence rates were focused on prospective cases. Of 574 pregnancies with maternal onabotulinumtoxinA exposure, 232 were eligible with known outcomes. Patients received onabotulinumtoxinA most frequently for cosmetic indications (50.5%), movement disorders (16.8%), and pain disorders (14.2%). Of the 137 with dose information, 40.1% received <50U, 14.6% 50U to <100U, 27.7% 100U to <200U, and 17.5% ≥200U. Among 146 cases with known maternal age, 47.9% were ≥35 years. Most (96.0%) fetal exposures occurred during/before the first trimester. Of the 137 prospective cases (139 fetuses), 110 (79.1%) were live births; 29 (20.9%; 95% CI, 14.0-30.0%) ended in fetal loss (21 spontaneous, 8 induced abortions). Among live births, 106 (96.4%) were normal, with four abnormal birth outcomes (1 major fetal defect, 2 minor fetal malformations, 1 birth complication), giving a 2.7% (3/110; 95% CI, 0.6-8.0%) prevalence rate for overall fetal defects. A 24-year retrospective review of the Allergan safety database shows that the prevalence of fetal defects in onabotulinumtoxinA-exposed mothers before/during pregnancy (2.7%) is comparable with background rates in the general population. Pregnancy outcome monitoring in onabotulinumtoxinA-exposed women continues.


The color appearance of stimuli detected via short-wavelength-sensitive cones: comparisons with visual adaptation and visual field data for peri- or post-menopausal women under 70 years of age.
Dynamics of foveal light adaptation for vision mediated via short-wavelength-sensitive (SWS) cones were compared for two groups of healthy amenorrheic (peri- or post-menopausal) women not using hormonal medication. Each subject was assigned to a group based on the color name-"lavender" ( approximately 2/3 of all subjects) or "white" (approximately 1/3 of all subjects)-chosen in a forced-response paradigm to best describe a threshold-level 440-nm test presented on a larger 3.6 log td 580-nm background that had been viewed for approximately 5 min. During the first 20-30s after this 3.6 log td background abruptly replaced a much dimmer background, the threshold elevations (relative to the steady-state levels measured at approximately 5 min) were significantly greater for the lavender-naming subjects than for the white-naming subjects. However, exponential rates of recovery were indistinguishable for the two groups. A viable interpretation is that the gain of the visual response at background onset is greater for lavender-naming subjects than for white-naming subjects at or distal to a site where responses from middle-wavelength-sensitive and long-wavelength-sensitive (MWS and LWS) cones oppose responses from SWS cones. In addition, the color names derived from foveal testing were related systematically to extrafoveal sensitivities measured with Short Wavelength Automated Perimetry (SWAP), in a manner suggesting that response gain and/or response speed may be greater for lavender-naming subjects in the direction of increased SWS response also. Evidence from other subject populations suggests that the choice of color name and the dynamics of visual response each can be affected by alterations (particularly reductions) of estrogen synthesis and response.


Avoiding blood products during liver transplantation.
Liver transplantation is a major surgical procedure usually requiring large amount of blood products (red cells, platelets, fresh-frozen plasma). We developed a multidisciplinary transfusion-free protocol for liver transplantation in Jehovah's witnesses who refuse the use of blood products but accept organ transplantation. Between September 1998 and November 2004, 9 of 29 Jehovah's witnesses evaluated for liver transplantation were transplanted after medical preparation. None of these patients received any blood product during the surgical procedure. This experience may be beneficial for the entire liver transplantation population, as excessive transfusion has been linked to increased morbidity and mortality in liver transplantation.


Calcium entry units (CEUs): perspectives in skeletal muscle function and disease.
In the last decades the term Store-operated Ca2+ entry (SOCE) has been used in the scientific literature to describe an ubiquitous cellular mechanism that allows recovery of calcium (Ca2+) from the extracellular space. SOCE is triggered by a reduction of Ca2+ content (i.e. depletion) in intracellular stores, i.e. endoplasmic or sarcoplasmic reticulum (ER and SR). In skeletal muscle the mechanism is primarily mediated by a physical interaction between stromal interaction molecule-1 (STIM1), a Ca2+ sensor located in the SR membrane, and ORAI1, a Ca2+-permeable channel of external membranes, located in transverse tubules (TTs), the invaginations of the plasma membrane (PM) deputed to propagation of action potentials. It is generally accepted that in skeletal muscle SOCE is important to limit muscle fatigue during repetitive stimulation. We recently discovered that exercise promotes the assembly of new intracellular junctions that contains colocalized STIM1 and ORAI1, and that the presence of these new junctions increases Ca2+ entry via ORAI1, while improving fatigue resistance during repetitive stimulation. Based on these findings we named these new junctions Ca2+ Entry Units (CEUs). CEUs are dynamic organelles that assemble during muscle activity and disassemble during recovery thanks to the plasticity of the SR (containing STIM1) and the elongation/retraction of TTs (bearing ORAI1). Interestingly, similar structures described as SR stacks were previously reported in different mouse models carrying mutations in proteins involved in Ca2+ handling (calsequestrin-null mice; triadin and junctin null mice, etc.) or associated to microtubules (MAP6 knockout mice). Mutations in Stim1 and Orai1 (and calsequestrin-1) genes have been associated to tubular aggregate myopathy (TAM), a muscular disease characterized by: (a) muscle pain, cramping, or weakness that begins in childhood and worsens over time, and (b) the presence of large accumulations of ordered SR tubes (tubular aggregates, TAs) that do not contain myofibrils, mitochondria, nor TTs. Interestingly, TAs are also present in fast twitch muscle fibers of ageing mice. Several important issues remain un-answered: (a) the molecular mechanisms and signals that trigger the remodeling of membranes and the functional activation of SOCE during exercise are unclear; and (b) how dysfunctional SOCE and/or mutations in Stim1, Orai1 and calsequestrin (Casq1) genes lead to the formation of tubular aggregates (TAs) in aging and disease deserve investigation.


Antioxidant activity and peptidomic analysis of porcine liver hydrolysates using alcalase, bromelain, flavourzyme and papain enzymes.
Antioxidant peptides are increasingly being recognized as food additives due to their effects on body human, regulating in vivo oxidative stress against oxidation of lipids and proteins. Meat by-products are rich sources of protein that can be employed for this purpose. Specifically, porcine liver can be used to prepare hydrolysates with antioxidant activity employing proteolytic enzymes such as alcalase, bromelain, papain and flavourzyme. In this study, the antioxidant activity of these four porcine liver hydrolysates was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ((2,2-azinobis-(3-ethyl-benzothiazoline-6-sulphonate) (ABTS), Ferric reducing antioxidant power assay (FRAP) and Oxygen radical absorbance capacity assay (ORAC) assays and the identification of bioactive peptides was carried out by SWATH-MS technology. According to the SDS-PAGE pattern, the proteolysis index and the free amino acids amount, the protein degradation was clearly different among the studied enzymes. Indeed, alcalase enzyme produced the release of small peptides, meanwhile flavourzyme produced higher level of free amino acids. The heatmap analysis showed a peptidomic pattern more differentiated for alcalase than for the other enzymes. The peptides most abundant and correlated with antioxidant capacity were APAAIGPYSQAVLVDR from uncharacterized protein, GLNQALVDLHALGSAR, ALFQDVQKPSQDEWGK and LSGPQAGLGEYLFER from ferritin and LGEHNIDVLEGNEQFINAAK from trypsinogen. The production and characterization of biopeptides is a new merging challenge of meat industry.


Author Correction: De novo assembly of transcriptomes, mining, and development of novel EST-SSR markers in Curcuma alismatifolia (Zingiberaceae family) through Illumina sequencing.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


C1q/tumor necrosis factor-related protein-1 attenuates microglia autophagy and inflammatory response by regulating the Akt/mTOR pathway.
C1q/tumor necrosis factor-related protein-1 (CTRP1) is a newly identified adiponectin paralog that modulates metabolism and inflammation. However, the cerebral function of CTRP1 remains unknown. This study aimed to determine its role and mechanism in cerebral ischemia and reperfusion injury. Serum level of CTRP1 as well as high-sensitivity C reactive protein (hs-CRP) in stroke patients was measured by ELISA assay. The levels of TNF-α, IL-1β, and IL-6 were analyzed using ELISA kits. Quantitative RT-PCR, western blot analysis were conducted to detect indicated genes. CTRP1 was significantly upregulated in sera from patients with stroke and positive correlation with hs-CRP. CTRP1 was significantly upregulated in BV2 microglia exposed to oxygen and glucose deprivation and reperfusion (OGD/R). Knockdown of CTRP1 by si-CTRP1 transfection markedly enhanced OGD/R-induced autophagy and accelerated the inflammatory response in BV2 cells, as indicated by increased expression of LC3-II/LC3-I and beclin1, as well as increased concentration of the proinflammatory cytokines TNF-α, IL-1β, and IL-6. However, recombinant CTRP1 or overexpression of CTRP1 attenuated OGD/R-induced autophagy and inflammatory response in BV2 cells. Further study demonstrated that knockdown of CTRP1 decreased, while recombinant CTRP1 increased the phosphorylation of Akt and mTOR in BV2 cells. IGF-1, which activates PI3-kinase and MEK1/2, abolished the promotive effect of si-CTRP1, while inhibition of Akt with A6730 reversed the inhibitory effect of recombinant CTRP1 on BV2 cells autophagy and inflammation response. CTRP1 inhibited microglia autophagy and inflammation response by regulating the Akt/mTOR pathway.


The role of reactive oxygen species in the anticancer activity of vitamin D.
Calcitriol, the hormonal form of vitamin D, enhances the anticancer activity of the immune cytokine tumor necrosis factor, interleukin 1 and interleukin 6 in human breast and renal cell carcinoma cells without affecting the cytotoxic action of interferon-alpha or killer lymphocytes. It also enhances cytotoxicity induced by the anticancer drug doxorubicin, by the redox cycling quinone menadione, and by the reactive oxygen species hydrogen peroxide. The synergistic interaction was accompanied by increased oxidative stress, as manifested by glutathione depletion and was abolished by exposure to the thiol antioxidant N-acetylcysteine. The hormone on its own brought about an increase in the cellular redox state as reflected in the ratio between oxidized and reduced glutathione and glyceraldehyde-3-phosphate dehydrogenase, and a reduction in the expression of the antioxidant enzyme Cu/Zn superoxide dismutase. These results support the notion that the interplay between active vitamin D derivatives and other anticancer agents such as immune cytokines and anticancer drugs plays a role in the in vivo anticancer activity of vitamin D and that reactive oxygen species are involved in the anticancer activity of vitamin D on its own and in its cross-talk with other anticancer modalities.


Relationship between serum nickel and homocysteine concentration in hemodialysis patients.
Severe hyperhomocysteinemia (HHC) is associated with atherosclerosis. In hemodialysis (HD) patients, one of the main causes of death is cardiovascular disease. In animals, trace elements such as cobalt, copper, iron, and nickel ameliorated vitamin B(12) deficiency-induced HHC. However, correlations between plasma total homocysteine (tHcy) and trace elements in HD patients have not been investigated. Therefore, tHcy, folate, vitamin B(12), trace elements (cobalt, copper, iron, and nickel), and some laboratory parameters such as serum total protein, albumin, transferrin, ferritin, C-reactive protein (CRP), and interleukin-6 concentrations were determined in 122 hemodialysis patients. When patients were divided into groups according to their tHcy, we found no significant differences in concentrations of cobalt, copper, and total protein, while nickel was higher, and folate, vitamin B(12), and iron were lower in patients with lower than higher tHcy. In univariate regression analysis, tHcy negatively correlated with concentrations of folate (r = -0.302, p < 0.006), vitamin B(12) (r = -0.347, p < 0.0001), nickel (r = -0.289, p < 0.006), and CRP (r = -0.230, p < 0.02) and positively with serum albumin (r = 0.316, p < 0.0004) and hemoglobin (r = 0.329, p < 0.0001) values. No relationship between tHcy and serum concentrations of cobalt, copper, iron, or other laboratory parameters was found in HD patients. The effect of cobalt and nickel on homocysteine production was assessed in human peripheral mononuclear cells (PBMCs). Nickel but not cobalt at concentrations found in HD patients significantly inhibited homocysteine, cysteine, and S-adenosylhomocysteine production in human PBMCs. These results suggest that nickel might also be involved in the regulation of the methionine-folate cycle in humans, as was demonstrated in animal experiments.


Collagen synthesis in the vaginal connective tissue of patients with and without uterine prolapse.
The insufficiency of connective tissue in pelvic relaxation was studied in five patients with uterine descent and in five age-related controls. Samples from vaginal fascias were first studied by histology. Fibroblast cultures started from each sample were analysed for their collagen synthesis and content of type I procollagen messenger RNAs (mRNAs). The cellularity of the fascias in histological specimens and the biosynthesis of collagen in fibroblast cultures decreased with increasing age in both groups. Fibroblasts grown from patients with uterine descent exhibited rates of collagen synthesis similar to or slightly higher than those from age-matched controls. The histological and biochemical changes observed in connective tissue of uterine descent are most likely related to the age and hormonal status of the patients. The findings suggest that uterine descent is not related to defects in the capacity of vaginal fibroblasts to synthesize or process procollagen.


The evidence for histamine H(3) receptor-mediated endothelium-dependent relaxation in isolated rat aorta.
The presence of histamine H(3) receptors was evaluated on the rat aorta endothelium. In the presence of pyrilamine (1 nM, 7 nM, 10 nM) or thioperamide (1 nM, 10 nM, 30 nM) the concentration-response curve for histamine-induced (0.1 nM - 0.01 mM) endothelium-dependent rat aorta relaxation was shifted to the right without significant change of the E(max) indicating competitive antagonism by pyrilamine (pA(2) = 9.33 +/- 0.34, slope = 1.09 +/- 0.36) or thioperamide (pA(2) =9.31 +/- 0.16, slope=0.94 +/- 0.10). Cimetidine (1 muM) did not influence histamine-induced endothelium-dependent rat aorta relaxation. In the presence of thioperamide (1 nM, 10 nM, 30 nM) the concentration-response curve for (R)alpha-MeHA-induced (0.1 nM - 0.01 mM) endothelium-dependent relaxation was shifted to the right without significant change of E(max) indicated competitive antagonism by thioperamide (pA(2) = 9.21 +/- 0.4, slope = 1.03 +/- 0.35). Pyrilamine (100 nM) or cimetidine (1 muM) did not influence (R)alpha-MeHA-induced endothelium-dependent rat aorta relaxation. These results suggest the presence of a heterogenous population of histamine receptors, H(1) and H(3), on rat aorta endothelium.


Morin ameliorates rotenone-induced Parkinson disease in mice through antioxidation and anti-neuroinflammation: gut-brain axis involvement.
Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting both motor and non-motor functions. It is well reported that the neuropathological process leading to PD starts from the gut before spreading to the CNS affirming the role of environmental toxicants such as rotenone. Morin (3, 5, 7, 2', 4'-pentahydroxyflavone) possesses neuroprotective and anti-oxidant activities which could be beneficial in PD. This study was designed to investigate the ameliorative influence of morin on rotenone-induced PD in mice. Male albino mice (18-23 g) were randomly divided into groups (n = 15) and treated for 28 consecutive days as follows: group 1: normal saline (10 ml/kg, p.o); group 2: rotenone (1 mg/kg, p.o, 0.5%w/v in CMC); groups 3-5: morin (5, 20 or 80 mg/kg, i.p.) + rotenone (1 mg/kg, p.o.), respectively, group 6: morin (20 mg/kg only, i.p.). Behavioural tasks were carried out weekly 1 h after treatments. Mice were euthanized on day 28 and discreet brain regions were assayed for oxidative stress parameters and immunohistochemical analysis. Morin reversed rotenone-induced behavioural deficits (motor incoordination, working memory deficit and depressive-like behaviour). Moreso, rotenone-induced lipid peroxidation (MDA), with a concomitant decrease in glutathione (GSH), superoxide dismutase (SOD) and acetylcholinesterase (AchE) activities in discreet regions of the brain were attenuated by the pre-treatment of mice with morin. Rotenone caused significant increase in the expression of iba-1, glial fibrillary acidic protein (GFAP), toll-like receptor 4 (TLR-4), and α-synuclein with a decrease in tyrosine hydroxylase positive neurons (TH) expression which were ameliorated by the pretreatment of mice with morin. Furthermore, rotenone-induced colon necrosis was reversed by morin administration. This study lend credence to the neuroprotective action of morin on rotenone-induced PD through enhancement of antioxidant defense and anti-inflammatory mechanisms.


Bispectral index and other processed parameters of electroencephalogram: an update.
The processed analysis of electroencephalogram became extremely important to monitor nervous system, being used to obtain a better anesthetic adequacy. The objective was to conduct a review about each processed parameter, defining its real importance. A review was conducted showing mathematical, physical and clinical aspects as well as their correlations and updates, presenting new integrated parameters. An adequate analysis of processed parameters of electroencephalogram may provide more intraoperative safety as well as result in a better outcome for the patient.


The enhancement of photovoltaic parameters in dye-sensitized solar cells of nano-crystalline SnO2 by incorporating with large SrTiO3 particles.
In this paper, the performance of nano-porous electrodes made of a composite material of SrTiO3 and SnO2 are compared with those made of bare SnO2. When these particular devices are analyzed in a comparative mode the results confirmed the enhancement of photovoltaic parameters in the former device. The performance of respective cells were examined by several methods including I-V characteristic measurements, photocurrent action spectra, dark I-V measurements, Mott-Schottky measurements and X-ray diffraction measurements. Even though such improvements in this particular cell could be explicated by the formation of a potential energy barrier of SrTiO3 particles of comparably large width at the SrTiO3/SnO2 interface, the passivation of voids in the SnO2 film by SrTiO3 particles to a certain extent could not be totally ruled out. Besides, high energetic electrons injected by dye molecules move more credibly through mini-bands formed in the chain of nano-crystalline SnO2 particles to the back contact. The blocking of the recombination path and the shifting up of the uppermost electron occupied level of SnO2 accompanying the conduction band edge in the SrTiO3/SnO2 composite film, may have lead to the observed enhancement of the fill factor and photovoltage, respectively.


Sports-related injuries in children.
Within a 3-year period, from 1980 to 1982, 1124 sports injuries of children aged 6-15 years were treated in the Turku University Central Hospital casualty department. Two-thirds (69%) of the injuries were sustained by boys. Sports injuries represented 21% of the diagnoses related to accidents in this age group. Half of the sports accidents occurred during the 4 winter months. Boys were injured most commonly in ice hockey (36%) and football (20%) and girls in skating (18%) and riding (18%). One quarter (26%) of the injuries were located in the head and neck, 36% in the upper extremities, 33% in the lower limbs, and 4% in the trunk. The most common types of injuries were fractures (26%), sprains and strains (24%), contusions (22%) and wounds (17%). The proportional occurrence of fractures increased with age in boys (P less than 0.001) and decreased in girls (P less than 0.001), luxations (P less than 0.05) and sprains (P less than 0.001) increased with age in girls; skull injuries (P less than 0.01) and contusions and wounds (P less than 0.001) decreased in boys. Girls had more sprains (P less than 0.001) but fewer contusions and wounds (P less than 0.001). Most of the injuries were mild; 9% of the cases were hospitalized. Minor surgery was performed in 16% and reconstructive surgery in 2% of all injuries. About 70% of the injuries occurred in nonorganized sports.


Simulations found within-subject measurement variation in glycaemic measures may cause overdiagnosis of prediabetes and diabetes.
To determine the impact of test measurement variation on misclassification of prediabetes and diabetes in the US adult population. Data from adults with no prior diagnosis of diabetes in the 2015 to 2016 National Health and Nutrition Examination Survey (NHANES) were used to simulate populations of US adults eligible for screening. Estimates of measurement variation were applied to each simulated individual's true values to generate observed values for up to five repeated screens. UNDERDIAGNOSIS: For 100,000 people assessed according to ADA or USPSTF guidelines, no people with true values in the diabetes range would be underdiagnosed as normal after one screen, and between 64 and 138 people would be misclassified with prediabetes after five re-screens (depending on guideline and test used). For 100,000 people assessed according to the guidelines, between 1,602 and 2,233 people with true values in the normal range would be over diagnosed with prediabetes after 3 re-screens. A further 627 to 1,672 people with true values in the prediabetes range would be over diagnosed with diabetes after 5 re-screens. Measurement variation may cause overdiagnosis of prediabetes and diabetes, as well as apparent "progression" or "regression" of either condition.


Intracellular Ser/Thr/Tyr phosphoproteome of the oral commensal Streptococcus gordonii DL1.
To respond and adapt to environmental challenges, prokaryotes regulate cellular processes rapidly and reversibly through protein phosphorylation and dephosphorylation. This study investigates the intracellular proteome and Ser/Thr/Tyr phosphoproteome of the oral commensal Streptococcus gordonii. Intracellular proteins from planktonic cells of S. gordonii DL1 were extracted and subjected to 2D-gel electrophoresis. Proteins in general were visualized using Coomassie Brilliant Blue and T-Rex staining. Phosphorylated proteins were visualized with Pro-Q Diamond Phosphoprotein Gel Stain. Proteins were identified by LC-MS/MS and sequence analysis. In total, sixty-one intracellular proteins were identified in S. gordonii DL1, many of which occurred at multiple isoelectric points. Nineteen of these proteins were present as one or more Ser/Thr/Tyr phosphorylated form. The identified phosphoproteins turned out to be involved in a variety of cellular processes. Nineteen phosphoproteins involved in various cellular functions were identified in S. gordonii. This is the first time the global intracellular Ser/Thr/Tyr phosphorylation profile has been analysed in an oral streptococcus. Comparison with phosphoproteomes of other species from previous studies showed many similarities. Proteins that are consistently found in a phosphorylated state across several species and growth conditions may represent a core phosphoproteome profile shared by many bacteria.


Expression of Cyp2c/Cyp2j subfamily members and oxylipin levels during LPS-induced inflammation and resolution in mice.
Inflammatory stimuli, such as bacterial LPS, alter the expression of many cytochromes P450. CYP2C and CYP2J subfamily members actively metabolize fatty acids to bioactive eicosanoids, which exhibit potent anti-inflammatory effects. Herein, we examined mRNA levels of the 15 mouse Cyp2c and 7 mouse Cyp2j isoforms in liver, kidney, duodenum, and brain over a 96-h time course of LPS-induced inflammation and resolution. Plasma and liver eicosanoid levels were also measured by liquid chromatography with tandem mass spectrometry. Expression changes in Cyp2c and Cyp2j isoforms were both isoform and tissue specific. Total liver Cyp2c and Cyp2j mRNA content was reduced by 80% 24 h after LPS but recovered to baseline levels by 96 h. Total Cyp2c and Cyp2j mRNA in kidney (-19%) and duodenum (-64%) were reduced 24 h after LPS but recovered above baseline by 72 h. Total Cyp2c and Cyp2j mRNA content in brain was elevated at all time points after LPS dosing. Plasma eicosanoids transiently increased 3-6 h after administration of LPS. In liver, esterified oxylipin levels decreased during acute inflammation and before recovering. The biphasic suppression and recovery of mouse Cyp2c and Cyp2j isoforms and associated changes in eicosanoid levels during LPS-induced inflammation and resolution may have important physiologic consequences.-Graves, J. P., Bradbury, J. A., Gruzdev, A., Li, H., Duval, C., Lih, F. B., Edin, M. L., Zeldin, D. C. Expression of Cyp2c/Cyp2j subfamily members and oxylipin levels during LPS-induced inflammation and resolution in mice.


Benefits of an oocyte pickup simulation training program using a high-fidelity simulator (PickUpSimTM) for obstetrics and gynaecology residents: an observational survey study.
The aim of this study was to evaluate an oocyte pick-up (OPU) simulation training program for residents using the high fidelity PickUpSimTM (Accurate, Cesena, Italy) simulator. The authors carried out an observational study during an OPU simulation workshop. A successful scenario was defined as an oocyte retrieval rate ≥70% without any complications. Forty-six residents affiliated to 23 different French university hospitals were included, and 37/46 (80.4%) of them successfully completed the scenario with a mean time of 3.4 ± 1.1 minutes. The oocyte retrieval rate was 442/561 (78.8%). All residents found training beneficial and 41/46 (87%) were in favour of having simulation-based training programs for OPU in their reproductive medicine departments. All residents who had previous experience with OPU (11/11) recommended the use of a simulator before performing OPU. This study confirms that high-fidelity OPU simulation is a simple and efficient method for training residents.Impact statementWhat is already known on this subject? Simulator-based training has been shown to be effective and useful for oocyte pick-up (OPU) training.What the results of this study add? All residents found the simulation program beneficial and formative, with 80% successfully completing their scenarios in a mean time of 3.4 ± 1.1 minutes. All residents who had previous experience with OPU recommended the use of a simulator before performing OPU.What the implications are of these findings for clinical practice and/or further research? Prospective studies are needed to confirm the short- and long-term positive clinical impact of OPU simulation training programs.


Medicare Advantage Chart Reviews Are Associated With Billions in Additional Payments for Some Plans.
In the Medicare Advantage (MA) program, private plans receive capitated payments that are adjusted based on their enrollees' number and type of clinical conditions. Plans have the ability to review charts to identify additional conditions that are not present in claims data, thereby increasing risk-adjusted payments. Recently the Government Accountability Office released a report raising concerns about the use of these chart reviews as a potential tool for upcoding. To measure the extent to which plans receive additional payments for chart reviews, and the variation in chart reviews across plans. In this cross-sectional study we use 2015 MA Encounter data to calculate how many additional diagnoses codes were added for each enrollee using chart reviews. We then calculate how these additional diagnosis codes translate to additional reimbursements across plans. A total of 14,021,692 beneficiaries enrolled in 510 MA contracts in 2015. Individual and contract level hierarchical condition category codes, total plan reimbursement. Chart reviews were associated with a $2.3 billion increase in payments to plans, a 3.7% increase in Medicare spending to MA plans. Just 10% of plans accounted for 42% of the $2.3 billion in additional spending attributed to chart review. Among these plans, the relative increase in risk score from chart review was 17.2%. For-profit plans engaged in chart reviews substantially more frequently than nonprofit plans. Given the substantial and highly variable increase in payments attributable to chart review, further investigation of the validity of this practice and its implications for Medicare spending is needed.


Early Transcatheter or Surgical Aortic Valve Replacement Versus Conservative Management in Asymptomatic Patients With Severe Aortic Stenosis: A Systematic Review and Meta-analysis.
The merits of conservative management vs early intervention in patients with asymptomatic severe aortic stenosis remains unknown. Digital databases (MEDLINE, Google Scholar, and Embase) were searched for all relevant studies from inception through September 2022. Studies comparing conservative management with early intervention were compared using a random-effects model to calculate risk ratios (RRs) with 95% confidence interval (CI). A total of 12 studies comprising 3624 asymptomatic aortic stenosis patients (1747 receiving surgery, and 1877 receiving conservative treatment) were included in the analysis. The average follow-up time was 4.45 (IQR 3.5-5) years. Early intervention was associated with a significantly reduced risk of cardiac (RR 0.42, 95% CI 0.25-0.72; P = 0.001; I2 = 54%), non-cardiac (RR 0.46, 95% CI 0.32-0.68; P < 0.0001; I2 = 0%), all-cause mortality (RR 0.40, 95% CI 0.32-0.51; P < 0.00001; I2 = 58%), heart failure hospitalization (RR 0.21, 95% CI 0.13-0.36; P < 0.00001; I2 = 0%), sudden cardiac death (RR 0.29, 95% CI 0.12-0.66; P = 0.004, I2 = 24%), and MACE (RR 0.46, 95% CI; 0.28-0.75; P = 0.002; I2 = 68%), compared with conservative management. There was no significant difference in the 30-day mortality (RR 0.63, 95% CI 0.19-2.04; P = 0.44; I2 = 28%), myocardial infarction (RR 0.44, 95% CI 0.19-1.06; P = 0.07, I2=0%), and 90-day mortality (RR 0.68, 95% CI 0.20-2.37; P = 0.55; I2 = 61%) between the 2 groups. This meta-analysis shows statistically significant reductions in the risk for all-cause mortality, cardiac specific mortality, non-cardiac mortality, heart failure hospitalization, MACE, and sudden cardiac death among asymptomatic aortic stenosis patients who underwent early intervention as opposed to conservative management.


The kinetics of ionophore X-537A-mediated transport of manganese through dipalmitoylphosphatidylcholine vesicles. A 1H-NMR study.
We have studied the kinetics of ionophore X-537A-mediated transport of manganese ions into small unilamellar vesicles formed from dipalmitoylphosphatidylcholine. To follow the transport we used the paramagnetic effect of manganese on the 1H-NMR signal from choline trimethylammonium groups on the inner phospholipid monolayer. The transport of only one manganese ion produces an intravesicular concentration which is high enough (approx. 1 mM) to substantially broaden this signal. The observed signal thus arises predominantly from those vesicles which contain no manganese. Therefore, as manganese is transported into the vesicles the observed signal decreases in intensity, but does not broaden. The initial time-dependence of the intensity of the signal, S(t), can be approximated by the simple first-order rate law: S(t) = S(0) exp(-k't), where k' is the probability per unit time for the transport of a manganese ion from the external medium to the intravesicular space. From the dependence of k' on the ionophore X-537A concentration we conclude that manganese is transported into the vesicles via both 1 : 1 and 2 : 1 complexes with ionophore X-537A. At low ratios of ionophore X-537A to vesicles transport via the 1 : 1 complex predominates; at high ratios transport via the 2 : 1 complex predominates. From the dependence of k' on manganese concentration we determined that under our conditions the equilibration of ionophore X-537A between vesicles is much faster than the transport of manganese through the vesicles. Lastly, from the dependence of k' on temperature, we conclude that the ionophore X-537A-mediated transport of manganese into the dipalmitoylphosphatidylcholine vesicles is very sensitive to the gel-liquid crystalline phase transition.


Association between self-reported night sleep duration and cognitive function among older adults with intact global cognition.
The purpose of this study was to clarify the association between self-reported night sleep duration and cognitive functions such as word memory, story memory, attention, executive function, and processing speed of older adults with normal global cognitive function. A total of 241 functionally independent older adults (mean age, 75.5 ± 6.4 years) participated in this study. No participants had a history of dementia diagnosis, and each had a Mini-Mental State Examination (MMSE) score ≥ 24. Participants were evaluated for self-reported sleep duration and cognitive function using the National Center for Geriatrics and Gerontology-Functional Assessment Tool (NCGG-FAT). The longest sleep duration group (≥9 h) had lower MMSE scores (p = 0.010), Z-score of word list memory II (delayed recall; p = 0.001), and Z-score of story memory II (delayed recognition; p = 0.002) than the medium sleep duration group (7-8 h). Longest and long sleep duration (8-9 h) was significantly associated with impairment of story memory II (longest sleep duration: adjusted odds ratio [OR] = 3.58, 95% confidence interval [CI] = 1.13-11.37, long sleep duration: adjusted OR = 4.30, 95% CI = 1.34-13.82) with reference to medium sleep duration, but no impairment of MMSE according to multiple logistic regression analysis. Furthermore, short sleep duration (<7 h) was not associated with cognitive impairment. This study suggests that long sleep duration is associated with cognitive impairment, especially of story memory (delayed recognition) in older adults with normal global cognitive function.


Flow cytometric analysis and optimisation for measuring phagocytosis in three Australian freshwater fish.
The phagocytic activity of fish immunocytes has been measured by a wide range of methods, and has been used as a bio-indicator to assess the immunotoxicity of environmental pollutants and the efficiency of immunostimulants used in aquaculture. This study demonstrates the utilisation of a flow cytometric technique for measuring phagocytosis as an alternative to manual evaluations by light microscopy. Optimal conditions for the phagocytosis of latex beads were ascertained, including incubation period, cell:bead ratio and media components, for head kidney cells isolated from three native Australian fish that inhabit the Murray-Darling basin, i.e. silver perch (Bidyanus bidyanus), golden perch (Macquaria ambigua) and crimson-spotted rainbowfish (Melanotaenia fluviatilis). Thus, standardised protocols have now been established for future use in the immunotoxicity testing of xenobiotics in native Australian freshwater fish.


Reproductive capacity and dominant lethal mutations in female guinea-pigs and Djungarian hamsters following X-rays or chemical mutagens.
The reproductive capacity and induction of dominant lethal mutations in adult female guinea-pigs and Djungarian hamsters were tested following treatment with 400 rad X-rays, 1.6 mg/kg triethylenemelamine (TEM) or 75 mg/kg isopropylmethanesulphonate (IPMS). A fairly high level of dominant lethals were observed in female guinea-pigs mated at the first oestrus after irradiation (23.4 +/- 6.4%) with a lower yield at 3 months (9.6 +/- 8.2%). Neither of the chemicals caused any significant induction of dominant lethals at either mating time. In the reproductive capacity experiments, the mean litter size of irradiated female guinea-pigs was reduced for about 12 months and this was especially marked in the first 6 months following treatment. Neither of the chemicals caused any significant differences in early litter sizes but there was a noticeable reduction in the litter sizes of TEM-treated females in the 18--24 month interval. With Djungarian hamsters a marked effect of X-rays on reproductive capacity was apparent. After 400 rad a smaller proportion of irradiated females littered in the first 25-day interval than after the other treatments, and no irradiated females produced more than one litter. Neither of the chemicals caused such a drastic reduction in fertility but TEM-treated females produced fewer litters and became sterile at an earlier age than control or IPMS-treated females. With IPMS, the number of litters produced was similar to the controls. Both chemicals caused a significant reduction in litter-size but further work is needed to establish whether this was due to induction of dominant lethals. No translocations were observed in the sons of treated female guinea-pigs or hamsters, but the numbers of animals studied were too small for any conclusions to be drawn.


Risk prediction for coronary heart disease by a genetic risk score - results from the Heinz Nixdorf Recall study.
A Genetic risk score for coronary artery disease (CAD) improves the ability of predicting coronary heart disease (CHD). It is unclear whether i) the use of a CAD genetic risk score is superior to the measurement of coronary artery calcification (CAC) for CHD risk assessment and ii) the CHD risk assessment using a CAD genetic risk score differs between men and women. We included 4041 participants (age-range: 45-76 years, 1919 men) of the Heinz Nixdorf Recall study without CHD or stroke at baseline. A standardized weighted CAD genetic risk score was constructed using 70 known genetic variants. The risk score was divided into quintiles (Q1-Q5). We specified low (Q1), intermediate (Q2-Q4) and high (Q5) genetic risk groups. Incident CHD was defined as fatal and non-fatal myocardial infarction, stroke and coronary death. The association between the genetic risk score and genetic risk groups with incident CHD was assessed using Cox models to estimate hazard ratios (HR) and 95%-confidence intervals (CI). The models were adjusted by age and sex (Model1), as well as by established CHD risk factors (RF) and CAC (Model2). The analyses were further stratified by sex and controlled for multiple testing. During a median follow-up time of 11.6 ± 3.7 years, 343 participants experienced CHD events (219 men). Per-standard deviation (SD) increase in the genetic risk score was associated with 18% increased risk for incident CHD (Model1: p = 0.002) which did not change after full adjustment (Model2: HR = 1.18 per-SD (p = 0.003)). In Model2 we observed a 60% increased CHD risk in the high (p = 0.009) compared to the low genetic risk group. Stratifying by sex, only men showed statistically significantly higher risk for CHD (Model2: HR = 1.23 per-SD (p = 0.004); intermediate: HR = 1.52 (p = 0.04) and high: HR = 1.88 (p = 0.008)) with no statistically significant risk observed in women. Our results suggest that the CAD genetic risk score could be useful for CHD risk prediction, at least in men belonging to the higher genetic risk group, but it does not outbalance the value of CT-based quantification of CAC which works independently on both men and women and allows better risk stratification in both the genders.


Pharmacokinetics of furegrelate after oral administration to normal humans.
Furegrelate sodium is a thromboxane synthetase inhibitor with potential for the treatment of various diseases including hypertension, thrombosis, and renal disorders. The absorption and disposition of the parent drug in normal male volunteers have been studied after single- and multiple-dose oral administration. The results from the single-dose study indicate that furegrelate is rapidly absorbed, with a Tmax of 1.0-1.7 hr, has an apparent terminal disposition rate constant of 0.12-0.17 hr-1, and is eliminated primarily by the kidney, with 62-78% of the dose excreted as parent drug. After multiple-dose oral administration for 4.5 days using a b.i.d. dosing regimen, no apparent change in the absorption, disposition, and elimination kinetics is detected and only a slight potential for drug accumulation is observed.


Cryoablation of septal pathways in patients with supraventricular tachyarrhythmias.
Eighteen patients with supraventricular tachycardia refractory to medical therapy underwent preoperative electrophysiological study and subsequent operation. There were 6 female and 12 male patients ranging in age from 1.5 to 31.6 years (mean age, 11.9 +/- 7.8 years). Eleven had classic Wolff-Parkinson-White syndrome with intermittent tachycardia, and 7 had a form of permanent junctional reciprocating tachycardia. Five had impaired left ventricular function preoperatively. The location of the accessory conduction pathway was anteroseptal in 3, posteroseptal in 12, and both anteroseptal and posteroseptal in 3 patients. Pathway location was confirmed by intraoperative mapping in all patients. The pathways were ablated utilizing a cryoprobe at -70 degrees C. All patients survived the operation, had immediate abolishment of delta waves and tachycardia, and were considered cured at the time of hospital discharge. Sixteen (89%) remain cured at a mean follow-up of 16.9 months. One patient with a posteroseptal pathway no longer has a delta wave but has had poorly documented episodes of tachycardia and is taking medication. One other patient with both anteroseptal and posteroseptal pathways had a recurrent delta wave 6 months postoperatively but has had no tachycardia and is asymptomatic without medication. No patient experienced heart block. Ventricular function has returned to normal in all 5 patients with impaired function preoperatively. Cryoablation is an effective method of abolishing accessory conduction pathways located in the anteroseptal or posteroseptal region. The method is easy, and results are comparable with those of other techniques previously described.


Electron microscope study of the association between hypothalamic blood vessels and oxytocin-like immunoreactive neurons.
An association between oxytocin-like immunoreactive neurons and hypothalamic blood vessels has been observed with the light microscope. Recently, it has been demonstrated that oxytocin stimulates vascular smooth muscle contraction in vitro. A hypothesis has thus been proposed that oxytocin may play a role in modulating blood flow in certain brain regions. In a study on the golden-mantled ground squirrel (Spermophilus lateralis) we noted the association at the light microscope level between oxytocin-like immunoreactive neurons and blood vessels in preoptic and paraventricular nuclei of the hypothalamus. To determine if these neurons were associated with hypothalamic capillaries, transverse 30 micron immunostained hypothalamic sections were prepared for thin sectioning and observation by transmission electron microscopy. Oxytocin-like immunoreactive neurons were observed to lie within 77 nm of the edge of the lumen of capillary blood vessels. One neuronal cell body was observed approximately 380 nm from the edge of a capillary lumen and what appears to be an output region of a neuron was observed to terminate on the basement membrane of a capillary blood vessel.


Diminished synaptosomal dopamine (DA) release and DA autoreceptor supersensitivity in schizophrenia.
Post-mortem brain regions of schizophrenics were investigated in comparison to matched controls regarding synaptosomal K(+)-stimulated [3H]DA release and its modulation by DA autoreceptors. Brain specimens were cryopreserved in liquid nitrogen until release experiments; synaptosomes from brain pieces preincubated with dimethylsulfoxide have unchanged ability for [3H]DA release and its autoreceptor-mediated inhibition after cryo-preservation. Release data were individually corrected for post-mortem delay back to the zero-time state based on [3H]DA release alterations after in situ preservation of rat heads. In schizophrenia, the K(+)-stimulated [3H]DA release from superfused synaptosomes of the nucleus (n.) accumbens and n. caudatus was diminished significantly. Furthermore, functional supersensitivity of the modulatory DA autoreceptors could be demonstrated in these regions. The alterations demonstrated seem not to be due primarily to medication since in neuroleptic-free patients similar changes were shown.


Development and Application of a LAMP Assay for the Detection of the Latent Apple Tree Pathogen Valsa mali.
Valsa mali, the causal agent of apple Valsa canker, produces cankers, resulting in the death of infected tissues and eventually the entire tree. Because of the long latent period of the disease, it is necessary to develop a rapid, sensitive, and reliable field-based assay to effectively diagnose apple Valsa canker when the plant is still symptomless. Loop-mediated isothermal amplification (LAMP) is a novel detection method that synthesizes a large amount of DNA and produces the visible byproduct (magnesium pyrophosphate) without conventional thermal cycling. Six LAMP primers were designed to target a species-specific region of the elongation factor-1α sequence, which can be completed at 61°C in 60 min. A positive result is indicated by color change after the intercalating dye SYBR Green I is added. The specificity of the LAMP was validated with DNA from 45 representative isolates of V. mali and closely related species V. malicola, V. leucostoma, and V. sordida. The sensitivity of the LAMP was determined to be 1 ng of DNA or as few as 10 spores. Because the assay does not require expensive equipment or specialized techniques, the LAMP-based diagnostic method can be applied under field conditions to more precisely and efficiently access disease pressure in apple orchards.


Emotional dysregulation in adult ADHD and response to atomoxetine.
Before 1980, attention-deficit/hyperactivity disorder (ADHD) was called minimal brain dysfunction and included emotional symptoms now listed as "associated features" in DSM-IV. Data from two multicenter, placebo-controlled studies with 536 patients were reexamined to assess: 1) the pervasiveness of these symptoms in samples of adults with ADHD; 2) the response of these symptoms to atomoxetine; and 3) their association with depressive/anxiety symptoms. The Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) was used to assess temper, affective lability, and emotional overreactivity, thus identifying patients exhibiting "emotional dysregulation." Other DSM-IV Axis I diagnoses were exclusionary. Outcome measures were the Conners' Adult ADHD Rating Scale (CAARS) and the WRAADDS. Thirty-two percent of the sample met post hoc criteria for emotional dysregulation and had higher baseline scores on ADHD measures, a lower response to placebo, and greater response to atomoxetine (p = .048). Symptoms of emotional dysregulation had a treatment effect (p < .001) at least as large as the CAARS (p = .002) and the total WRAADDS (p = .001). Emotional dysregulation was present in the absence of anxiety or depressive diagnosis. Symptoms of emotional dysregulation were present in many patients with ADHD and showed a treatment response similar to other ADHD symptoms.


Study of alpha hemoglobin stabilizing protein expression in patients with β thalassemia and sickle cell anemia and its impact on clinical severity.
The α hemoglobin stabilizing protein (AHSP) binds α-Hb and prevents its precipitation limiting free α-Hb toxicities. Our aim was to study AHSP expression in β thalassemia syndromes in relation to their clinical severity and to compare it with its level in sickle cell anemia. We compared patients with β-thalassemia (n=37) (β-thalassemia major (BTM) (n=19) and β-thalassemia intermedia (BTI) (n=18)) with 12 patients with sickle cell anemia as regards clinical severity, age at presentation, transfusion dependency, mean pre-transfusion hemoglobin level, use of hydroxyurea and AHSP expression by real time quantitative PCR. Median (and IQR) AHSP expression was significantly higher in patients with sickle cell anemia 2275 (3898) compared to thalassemia 283 (718), P=0.001, with no significant difference between BTM and BTI (P=0.346). It was also significantly higher in non-transfusion dependent patients with β thalassemia (NTDT) compared to transfusion dependent ones (P=0.019), and in patients on hydroxyurea therapy (P<0.001). However, there was no significant difference in its level according to clinical severity score (P=0.946) or splenectomy status (P=0.145). AHSP expression was higher in patients with sickle cell anemia versus thalassemia, with no significant difference between BTM and BTI. Expression was higher in patients with NTDT and on hydroxyurea therapy.


Draft Genome Sequence of an Invasive Streptococcus agalactiae Isolate Lacking Pigmentation.
This report provides the whole-genome sequence of Streptococcus agalactiae isolate GB00037 isolated from a newborn in Calgary, Canada. This serotype V isolate is unique because it lacks pigment production previously shown to be critical for S. agalactiae virulence.


Role of Age on Success of Arthroscopic Primary Repair of Proximal Anterior Cruciate Ligament Tears.
To assess failure rates and patient-reported outcomes measures following arthroscopic primary anterior cruciate ligament (ACL) repair of proximal tears in different age groups. Between 2008 and 2017, the first 113 consecutive patients treated with repair were retrospectively reviewed at minimum of 2 years. Patients were stratified into 3 age groups: ≤21, 22-35, and >35 years. Primary outcomes were ipsilateral reinjury or reoperation, and contralateral injury rates, and secondary outcomes consisted of Lysholm, modified Cincinnati, Single Assessment Numeric Evaluation, International Knee Documentation Committee subjective, pain, and satisfaction scores. Group differences were compared using χ2 tests and Mann-Whitney U tests. Follow-up was obtained in 113 patients (100%). Median age was 35 years (interquartile range [IQR] 23-43) and median follow-up was 2.2 years (IQR 2.0-2.8). Overall, ACL reinjury occurred in 13 patients (11.5%), reoperation in 7 patients (6.2%), complications in 2 patients (1.8%) and contralateral ACL injury in 4 patients (3.5%). Overall, median Lysholm was 95 (IQR 89-100) and International Knee Documentation Committee subjective 92 (IQR 84-99). Treatment failure was significantly greater in the youngest age group (37.0%) as compared with the middle and older groups (4.2% and 3.2%, both P < .005). No significant differences were seen in reoperation, complication, or contralateral injury rates between groups (all P > .2), nor in patient-reported outcomes measures between the groups (all P > .1). The failure rate of primary repair of proximal ACL tears is high in patients aged 21 or younger (37.0%), and this should be taken into account when discussing repair in this patient group. In patients older than 21, repair may be an excellent treatment with low failure (3.5%) and complication rates (1.2%) and good subjective scores. Level III, retrospective comparative therapeutic trial.


Proteomic profile of vitreous in patients with tubercular uveitis.
To elucidate disease-specific host protein profile in vitreous fluid of patients with intraocular inflammation due to tubercular uveitis (TBU). Vitreous samples from 13 patients with TBU (group A), 7 with non-TBU (group B) and 9 with no uveitis (group C) were analysed by shotgun proteomics using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) were subjected to pathway analysis using WEB-based Gene SeT Analysis Toolkit software. Compared to control groups (B + C combined), group A (TBU) displayed 32 (11 upregulated, 21 downregulated) DEPs, which revealed an upregulation of coagulation cascades, complement and classic pathways, and downregulation of metabolism of carbohydrates, gluconeogenesis, glucose metabolism and glycolysis/gluconeogenesis pathways. When compared to group B (non-TBU) alone, TBU displayed 58 DEPs (21 upregulated, 37 downregulated), with an upregulation of apoptosis, KRAS signaling, diabetes pathways, classic pathways, and downregulation of MTORC1 signaling, glycolysis/gluconeogenesis, and glucose metabolism. This differential protein profile provides novel insights into the molecular mechanisms of TBU and a baseline to explore vitreous biomarkers to differentiate TBU from non-TBU, warranting future studies to identify and validate them as a diagnostic tool in TBU. The enriched pathways generate interesting hypotheses and drive further research.


Geometric characterization of dynamical structure for neural firing activities induced by inhibitory pulse.
In general, inhibitory stimuli are thought to inhibit neuronal firing, but they may actually enhance firing sometimes, such as post-inhibitory rebound spike (PIR spike) and post-inhibitory facilitation (PIF) phenomena, which play an important role in human neuronal activities. We study responses to inhibitory pulse in a classical neuron model (Quartic adaptive Integrate-and-fire model) well known to reproduce a number of biologically realistic behaviors. The three phenomena that we study are PIR, in which a neuron fires after an inhibitory pulse, and PIF, in which a subthreshold excitatory input can induce a spike if it is applied with proper timing after an inhibitory pulse, as well as period firing after inhibitory pulse. When the system features focus and saddle two equilibriums, the three phenomena will be occurred under the inhibitory pulse, while all three phenomena will not be induced when the system features node and saddle two equilibriums. Using dynamical systems theory, we explain the threshold mechanism of enhancement of neural firing response induced by inhibitory pulse and analyze the origin of these phenomena from several factors. We also describe the geometric characterization of dynamical structures of these three phenomena. This study therefore enrich the paradoxical phenomena that induced by inhibitory input and advance our understanding of its role.


Synthesis of new thermo/pH sensitive drug delivery systems based on tragacanth gum polysaccharide.
In this study, new pH/temperature responsive graft copolymers were synthesized based on natural Tragacanth Gum (TG) carbohydrate and their controlled drug release was investigated. Amphiphilic alkyne terminated terpolymers (mPEG-PCL-PDMAEMA-CCH)s consist of methylated poly(ethyleneglycol) (mPEG), polycaprolactone (PCL), and poly(dimethylaminoethylmethacrylate) (PDMAEMA) were synthesized by using ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP), and then were grafted onto azide-functionalized TG molecules by click chemistry. Different techniques such as FT-IR, (1)H NMR, gel permeation chromatography (GPC), thermo-gravimetrical analysis (TGA) and scanning electron microscopy (SEM) were used to verify the successful synthesis of graft copolymers (TG-g-PDMAEMA-PCL-mPEG)s. The graft copolymers self-assembled to single micelles in aqueous solution and upon pH changes further assembled into micellar aggregates. These micelles were used to prepare quercetin loaded nanocarriers by probe sonication method. Size and morphology of the nanocarriers were studied by dynamic light scattering (DLS) and SEM. The in vitro release behavior of quercetin from these micelles showed pH-dependence. The results showed that release profile of quercetin best followed the first order model.


CD8+T cells from patients with cirrhosis display a phenotype that may contribute to cirrhosis-associated immune dysfunction.
Cirrhosis-associated immune dysfunction (CAID) contributes to high sepsis risk in patients with chronic liver disease. Various innate and; to a lesser extent; adaptive immune dysfunctions have been described as contributors to CAID leading to immune-paresis and impaired anti-microbial response in cirrhosis. In this study, we examined the phenotype of CD8+T cells in chronic liver disease with the aim to evaluate changes that might contribute to impaired immune responses. Sixty patients with cirrhosis were prospectively recruited for this study. CD8+T cells from peripheral blood, ascites and liver explants were characterized using flow cytometry and immunohistochemistry, respectively. The transcriptional signature of flow-sorted HLA-DR+CD8+T cells was performed using Nanostring™ technology. HLA-DR+CD8+T cells interactions with PBMCs and myeloid cells were tested in vitro. Peripheral CD8+T cells from cirrhotic patients displayed an altered phenotype characterized by high HLA-DR and TIM-3 surface expression associated with concomitant infections and disease severity, respectively. Paired peritoneal CD8+T cells expressed more pronounced levels of HLA-DR and PD-1 compared to peripheral CD8+T cells. HLA-DR+CD8+T cells were enriched in cirrhotic livers compared to controls. TIM-3, CTLA-4 and PD-1 levels were highly expressed on HLA-DR+CD8+T cells and co-expression of HLA-DR and PD1 was higher in patients with poor disease outcomes. Genes involved in cytokines production and intracellular signalling pathways were strongly down-regulated in HLA-DR+CD8+T cells. In comparison to their HLA-DR- counterparts, HLA-DR+CD8+T cells promoted less proliferation of PBMCs and induced phenotypic and functional dysfunctions in monocytes and neutrophils in vitro. In patients with cirrhosis, CD8+T cells display a phenotypic, functional and transcriptional profile which may contribute to CAID. FUND: This work was supported by Medical Research Council, the Rosetrees Charitable Trust, Robert Tournut 2016 grant (Sociéte Nationale Française de GastroEntérologie), Gilead® sciences, and NIHR Imperial Biomedical Research Centre.


The p160 nuclear receptor co-activator RAC3 exerts an anti-apoptotic role through a cytoplasmatic action.
The p160 nuclear receptor co-activators represent a family of molecules, which are recruited by steroid nuclear receptors as well as other transcription factors that are overexpressed in several tumors. We investigated the role of one member of this family on the sensitivity of cells to apoptosis. We observed that overexpression of the RAC3 (receptor-associated co-activator-3) p160 co-activator inhibits hydrogen peroxide-induced cell death in human embryonic kidney 293 (HEK293) cells. The mechanism involves the activation of anti-apoptotic pathways mediated through enhanced nuclear factor kappa B (NF-kappaB) activity, inhibition of caspase-9 activation, diminished apoptotic-inducing factor (AIF) nuclear localization and a change in the activation pattern of several kinases, including an increase in both AKT and p38 kinase activities, and inhibition of ERK2. Moreover, RAC3 has been found associated with a protein complex containing AIF, Hsp90 and dynein, suggesting a role for the co-activator in the cytoplasmatic nuclear transport of these proteins associated with cytoskeleton. These results demonstrate that there are several molecular pathways that could be affected by their overexpression, including those not restricted to steroid regulation or the nuclear action of co-activators, which results in diminished sensitivity to apoptosis. Furthermore, this could represent one mechanism by which co-activators contribute to tumor development.


Role of inflammatory mediators in patients with recurrent pregnancy loss.
To examine interleukin-12 (IL-12), IL-18, IFN-γ, intracellular adhesion molecule-1 (ICAM-1), leukemia inhibitory factor (LIF), and migration inhibitory factor (MIF) levels in precisely-timed blood and endometrial tissue samples from women with idiopathic recurrent pregnancy loss (RPL). Case-control study. University hospital. Twenty-one women with RPL and 20 women with proven fertility (controls). Primary endometrial cells and blood samples during the midsecretory phase (days 19-23). Detection of IL-12, IL-18, IFN-γ, ICAM-1, LIF, and MIF via enzyme-linked immunosorbent assay in both blood and endometrial tissue samples. The blood and tissue levels of IL-12, IL-18, and IFN-γ were statistically significantly higher, and the blood and tissue levels of LIF and MIF were statistically significantly lower in patients with RPL. Only the level of tissue ICAM-1 was higher in patients with RPL. There was a strong correlation between blood and tissue level measurements of IL-12, IL-18, LIF, and MIF. Our findings support the hypothesis that inflammatory processes may contribute to pregnancy loss, possibly through their role in implantation. We found that blood and tissue levels of IL-18, LIF, and MIF, and tissue levels of IL-12, IFN-γ, and ICAM-1 have statistically significant prognostic relevance.


Evolutionarily conserved features contribute to αβ T cell receptor specificity.
αβ T cell receptors (TCRs) bind specifically to foreign antigens presented by major histocompatibility complex proteins (MHC) or MHC-like molecules. Accumulating evidence indicates that the germline-encoded TCR segments have features that promote binding to MHC and MHC-like molecules, suggesting coevolution between TCR and MHC molecules. Here, we assess directly the evolutionary conservation of αβ TCR specificity for MHC. Sequence comparisons showed that some Vβs from distantly related jawed vertebrates share amino acids in their complementarity determining region 2 (CDR2). Chimeric TCRs containing amphibian, bony fish, or cartilaginous fish Vβs can recognize antigens presented by mouse MHC class II and CD1d (an MHC-like protein), and this recognition is dependent upon the shared CDR2 amino acids. These results indicate that features of the TCR that control specificity for MHC and MHC-like molecules were selected early in evolution and maintained between species that last shared a common ancestor more than 400 million years ago.


[Pulmonary and cerebral aspergillosis in Burkitt's lymphoma].
Multiple intracerebral aspergillus abscesses in a 5 year old boy with a Burkitt's lymphoma are described. The disease was fatal despite antifungal treatment. The diagnostic and therapeutic problems, the risk factors and preventive care are discussed.


Deep learning segmentation of major vessels in X-ray coronary angiography.
X-ray coronary angiography is a primary imaging technique for diagnosing coronary diseases. Although quantitative coronary angiography (QCA) provides morphological information of coronary arteries with objective quantitative measures, considerable training is required to identify the target vessels and understand the tree structure of coronary arteries. Despite the use of computer-aided tools, such as the edge-detection method, manual correction is necessary for accurate segmentation of coronary vessels. In the present study, we proposed a robust method for major vessel segmentation using deep learning models with fully convolutional networks. When angiographic images of 3302 diseased major vessels from 2042 patients were tested, deep learning networks accurately identified and segmented the major vessels in X-ray coronary angiography. The average F1 score reached 0.917, and 93.7% of the images exhibited a high F1 score > 0.8. The most narrowed region at the stenosis was distinctly captured with high connectivity. Robust predictability was validated for the external dataset with different image characteristics. For major vessel segmentation, our approach demonstrated that prediction could be completed in real time with minimal image preprocessing. By applying deep learning segmentation, QCA analysis could be further automated, thereby facilitating the use of QCA-based diagnostic methods.


Erratum: [Corrigendum] Expression of family with sequence similarity 172 member A and nucleotide‑binding protein 1 is associated with the poor prognosis of colorectal carcinoma.
[This corrects the article DOI: 10.3892/ol.2017.6585.].


Long term follow-up of inferior myocardial infarction. Prognostic significance of precordial ST segment depression.
A group of 123 consecutive patients with acute transmural inferior myocardial infarction were compared according to the presence or absence of precordial ST segment depression on admission to hospital. There was a significant increase in mean age, peak creatine kinase levels, and the incidence of left ventricular failure and high grade atrioventricular block in the group with precordial ST segment depression. There was also an increase in in-hospital mortality in this group but this difference was not significant. Despite these differences in in-hospital progress, during a follow-up period of over two years there was no difference in long term mortality, recurrence of angina, or subsequent cardiac-related admissions between the two groups.


Review of four unusual cases of HIV-positive infants; cryptic pregnancy scam and mother-to-child transmission of HIV in Nigeria.
Cryptic pregnancy is defined as lack of awareness of pregnancy until the last weeks of gestation or during labour and delivery but in cryptic pregnancy scam, mothers feigned pregnancies that never existed. We report a total of four cases of HIV infected infants said to have been delivered by HIV negative mothers. All the mothers are above 40 years of age with a range of 9 to 18 years of infertility in marriage. The cryptic pregnancy scam was neither confirmed by pregnancy test nor obstetric scan. Diagnosis of HIV infection was made at infancy following positive rapid test and HIV antigen test. The menace of cryptic pregnancy scam in Nigeria is setting back the gains of HIV prevention and control. Desperate infertile women are made to believe that they are pregnant while babies are bought and brought to them at said date of delivery. These mothers never had proper antenatal care and so were never screened for HIV. Cryptic pregnancy scam is real amongst desperate barren women who become easy prey to the perpetuators. Awareness creation and sensitization on its harm is advocated.


Stonefish toxin defines an ancient branch of the perforin-like superfamily.
The lethal factor in stonefish venom is stonustoxin (SNTX), a heterodimeric cytolytic protein that induces cardiovascular collapse in humans and native predators. Here, using X-ray crystallography, we make the unexpected finding that SNTX is a pore-forming member of an ancient branch of the Membrane Attack Complex-Perforin/Cholesterol-Dependent Cytolysin (MACPF/CDC) superfamily. SNTX comprises two homologous subunits (α and β), each of which comprises an N-terminal pore-forming MACPF/CDC domain, a central focal adhesion-targeting domain, a thioredoxin domain, and a C-terminal tripartite motif family-like PRY SPla and the RYanodine Receptor immune recognition domain. Crucially, the structure reveals that the two MACPF domains are in complex with one another and arranged into a stable early prepore-like assembly. These data provide long sought after near-atomic resolution insights into how MACPF/CDC proteins assemble into prepores on the surface of membranes. Furthermore, our analyses reveal that SNTX-like MACPF/CDCs are distributed throughout eukaryotic life and play a broader, possibly immune-related function outside venom.


Religious affiliation and women's receipt of person-centered contraceptive care: Findings from the National Survey of Family Growth, 2017-2019.
To assess patient ratings of person-centered contraceptive care among women of different religious affiliations in the United States. Data from the 2017-2019 National Survey of Family Growth and a sample of female respondents ages 15-49 years who received contraceptive services in the past year and completed the Person-Centered Contraceptive Counseling scale (N = 2226). Catholic and Protestant women had higher odds of reporting overall person-centered contraceptive care (odds ratio [OR] = 1.77, OR = 1.54) compared to respondents without a religious affiliation and net sociodemographic characteristics. Women's experiences with person-centered contraceptive care differ based on their religious affiliation. Advancing research on the barriers to person-centered contraceptive care is essential for providing quality health care and reproductive autonomy. This analysis suggests that researchers and clinicians should consider how patient religious affiliation shapes patient-provider encounters and patient experiences of person-centered care to promote quality, equitable family planning care.


Characteristics and radiofrequency ablation therapy of intermediate septal accessory pathway.
Fourteen patients (5%) with an intermediate septal accessory pathway were identified among 283 consecutive patients with the Wolff-Parkinson-White syndrome who had electrophysiologic study and radiofrequency ablation therapy. Nine were women and 5 were men (mean age 33 +/- 13 years). The resting electrocardiogram showed ventricular preexcitation in 8 patients and normal PR interval in 6. Anterograde and retrograde mapping studies revealed that the accessory pathway was para-Hisian in 11 patients and paranodal in 3. The accessory pathway was successfully ablated in 10 patients (9 para-Hisian and 1 paranodal) and damaged in 1 (para-Hisian). Treatment of 3 patients was complicated by transient atrioventricular (AV) block, of 1 by intermittent second-degree AV block, and of another by permanent complete AV block requiring implantation of a permanent pacemaker. Six patients underwent a follow-up electrophysiologic study 84 +/- 55 days after ablation; none had induction of tachycardia even after isoproterenol infusion. It is concluded that radiofrequency ablation therapy for intermediate septal accessory pathway is feasible. However, the success rate is only modest (71%), whereas complications with heart block (36%) or complete right bundle branch block (29%) are high. Thus, the procedure should be reserved for patients with life-threatening or troublesome symptomatic tachyarrhythmias.


Migration of abdominal catheter of ventriculoperitoneal shunt into the scrotum.
Two cases are reported in which the abdominal catheters slipped into the scrotum through the unobliterated processus vaginalis.


Bronchogenic carcinoma staging: CT versus MR imaging. Assessment with surgery.
One hundred and twenty patients with bronchogenic carcinoma were prospectively studied by both computed tomography (CT) and magnetic resonance imaging (MRI) during the 2 weeks preceding thoracotomy or mediastinoscopy. MRI scans included contiguous axial and coronal slices. Results of CT and MRI studies were compared with the surgical and pathological findings on the basis of the TNM classification. Although no significant difference was found between the two imaging methods for the evaluation of tumour extent, MRI appears to be a valuable imaging technique for left upper lobe and apical neoplasms. Comparison between the two techniques for mediastinal node evaluation showed that sensitivity of MRI is superior to CT in the left paratracheal, aortopulmonary and subcarinal node areas.


[Spontaneous evacuation of ascites through an umbilical hernia].
A case of spontaneous rupture of the umbilicus is reported as an unusual and frequently fatal complication of massive ascites due to hepatic cirrhosis. The patient survived this episode with medical treatment.


Factors associated with not meeting the recommendations for micronutrient intake in critically ill children.
Children admitted to the intensive care unit (ICU) are at risk of not meeting their nutritional requirements. This study aimed to identify factors associated with failure to meet the dietary recommended intake (DRI) of zinc, selenium, cholecalciferol, and thiamine in critically ill children receiving enteral tube feeding during their stay in the ICU. We analyzed prospectively 260 cases, corresponding to 206 patients who received enteral tube feeding for a minimum of 3 days up to 10 days during the first 10 d of ICU stay. Individual intake was compared to estimated average requirement (EAR) and adequate intake (AI) values during the first 10 d of ICU stay. The outcome variable was defined as not meeting the recommended intake of the micronutrients studied. Potential explanatory variables for the outcome were age <1 year, malnutrition (WHO), clinical severity scores, heart disease, severe sepsis or septic shock, use of alpha-adrenergic drugs, and renal replacement therapy (RRT). The effect of the explanatory variables on the outcome was analyzed by logistic regression analysis. The majority of patients did not meet the recommendations for micronutrients. After adjusting for covariates, age <1 year, malnutrition, heart disease, use of alpha-adrenergic drugs, and renal replacement therapy were associated with failure to meet the recommendations for at least one of the micronutrients studied. Factors associated with failure to meet the recommendations for micronutrient intake in children receiving enteral tube feeding during their ICU stay are linked to patients' low weight, restriction in fluid intake, and clinical severity of the disease.


'It just stops me from living': A qualitative study of losses experienced by women with self-reported endometriosis.
To understand the experience of loss in Australian women with endometriosis. A total of 532 participants completed an online survey containing three open-ended questions relating to pelvic pain and activity loss due to endometriosis. Participants were Australian women aged between 18 and 50 years (M = 30.8, SD = 7.1) with a self-reported diagnosis of endometriosis. An inductive, qualitative approach, with template analysis was used to identify and organize themes. A pragmatic feminist perspective was used to interpret the findings. Three main themes were identified: the loss of liberty: 'I'm trapped in the house'; the loss of bodily autonomy: 'I can barely move/breathe/talk' and loss of connection: 'It stops me from being social'. Pain emerged as the greatest concern for participants, preventing them from the physical functioning required to participate in many of life's activities. The losses women with endometriosis experience are wide-reaching, restricting control and choice across multiple life domains. Losses were often unacknowledged by loved ones and healthcare providers, further impacting the physical, emotional and mental health of participants. People with endometriosis were involved in the design of the study, including identifying topics of interest.


Exome sequencing in a family with intellectual disability, early onset spasticity, and cerebellar atrophy detects a novel mutation in EXOSC3.
Whole exome sequencing in two-generational kindred from Bangladesh with early onset spasticity, mild intellectual disability, distal amyotrophy, and cerebellar atrophy transmitted as an autosomal recessive trait identified the following two missense mutations in the EXOSC3 gene: a novel p.V80F mutation and a known p.D132A change previously associated with mild variants of pontocerebellar hypoplasia type 1. This study confirms the involvement of RNA processing proteins in disorders with motor neuron and cerebellar degeneration overlapping with spinocerebellar ataxia 36 and rare forms of hereditary spastic paraplegia with cerebellar features.


Anterior segment findings in AIDS patients with cytomegalovirus retinitis.
Anterior segment findings in AIDS patients presenting with cytomegalovirus (CMV) retinitis have not been specifically addressed in the American literature. Our study evaluated 21 AIDS patients with CMV retinitis. Nineteen (90%) of these patients exhibited corneal endothelial deposits concurrent with CMV retinitis. The endothelial deposits were microscopic, opaque, linear flecks arranged in a reticular-like fashion. Of 42 eyes evaluated, 32 (76%) demonstrated active CMV retinitis. Corneal endothelial deposits were noted in 26 (81%) of the 32 eyes with retinitis. These corneal endothelial deposits were absent in the eyes which did not have CMV retinitis. Meticulous examination of the retina of an HIV-positive or AIDS patient who presents with reticularly arranged, linear, flecked corneal endothelial deposits should be performed to ensure that the diagnosis of CMV retinitis can be ruled out.