Human vascular smooth muscle cells express interleukin-1beta-converting enzyme (ICE), but inhibit processing of the interleukin-1beta precursor by ICE.
Local immunoregulatory processes during normal vascular biology or pathogenesis are mediated in part by the production of and response to cytokines by vessel wall cells. Among these cytokines interleukin (IL)-1 is considered to be of major importance. Although vascular smooth muscle (SMC) and endothelial cells (EC) expressed both IL-1alpha and IL-1beta as cell-associated, 33-kilodalton (kD) precursors, SMC neither contained detectable mature IL-1beta, nor processed recombinant IL-1beta precursor into its mature 17-kD form. Thus, we investigated the expression and function of IL-1beta-converting enzyme (ICE) in vascular cells. We demonstrate in processing experiments with recombinant IL-1 precursor molecules that EC processed IL-1beta, in contrast to SMC. Despite the failure of SMC to process IL-1beta, these cells expressed ICE mRNA, immunoreactive ICE protein, and the expected IL-1beta nucleotide sequence. The lack of processing was explained by our finding that extracts of SMC specifically and concentration dependently blocked processing of IL-1beta precursor by recombinant or native ICE. The initial biochemical characterization of the inhibitory activity showed that it is heat-labile, has a molecular size of 50-100 kD, and is associated to the cell membrane compartment. Inhibition of processing, i.e., activation of IL-1beta precursor by SMC may constitute a novel regulatory mechanism during normal vascular biology or pathogenesis of vascular diseases.


Proteostasis collapse is a driver of cell aging and death.
What molecular processes drive cell aging and death? Here, we model how proteostasis-i.e., the folding, chaperoning, and maintenance of protein function-collapses with age from slowed translation and cumulative oxidative damage. Irreparably damaged proteins accumulate with age, increasingly distracting the chaperones from folding the healthy proteins the cell needs. The tipping point to death occurs when replenishing good proteins no longer keeps up with depletion from misfolding, aggregation, and damage. The model agrees with experiments in the worm Caenorhabditis elegans that show the following: Life span shortens nonlinearly with increased temperature or added oxidant concentration, and life span increases in mutants having more chaperones or proteasomes. It predicts observed increases in cellular oxidative damage with age and provides a mechanism for the Gompertz-like rise in mortality observed in humans and other organisms. Overall, the model shows how the instability of proteins sets the rate at which damage accumulates with age and upends a cell's normal proteostasis balance.


Epigenetic inheritance: histone bookmarks across generations.
Multiple circuitries ensure that cells respond correctly to the environmental cues within defined cellular programs. There is increasing evidence suggesting that cellular memory for these adaptive processes can be passed on through cell divisions and generations. However, the mechanisms by which this epigenetic information is transferred remain elusive, largely because it requires that such memory survive through gross chromatin remodeling events during DNA replication, mitosis, meiosis, and developmental reprogramming. Elucidating the processes by which epigenetic information survives and is transmitted is a central challenge in biology. In this review, we consider recent advances in understanding mechanisms of epigenetic inheritance with a focus on histone segregation at the replication fork, and how an epigenetic memory may get passed through the paternal lineage.


Do malaria preventive interventions reach the poor? Socioeconomic inequities in expenditure on and use of mosquito control tools in Sudan.
To determine levels of socioeconomic inequities in the prevention of malaria, and to examine the implications of the findings for improving the equitable control of malaria in the Sudan. A cross-sectional survey using a pre-tested interviewer-administered questionnaire was administered to 720 randomly selected householders from six localities in Gezira and Khartoum States. A socioeconomic status (SES) index, which was developed using principal components analysis, was used to examine socioeconomic inequity in the prevention of malaria. Socioeconomic status was positively related to expenditures and use of vector control tools. The poorest households spent the least amounts of money to prevent malaria and were the least likely to own mosquito nets. The inequity in the prevention of malaria in the study areas has to be redressed before malaria can be effectively controlled in Sudan. Malaria control managers should continually determine the extent to which malaria preventive tools reach the poorest socioeconomic groups, and fashion strategies that will ensure that equity is always maintained.


Low-dose versus conventional-dose prednisolone for nephrotic syndrome relapses: a randomized controlled non-inferiority trial.
Reduction of steroid exposure in relapses of steroid-sensitive nephrotic syndrome (SSNS) is under-researched. In this randomized controlled non-inferiority trial, 1-12-year-old children with relapse of SSNS were randomized to receive prednisolone 1 mg/kg/day (low dose) or 2 mg/kg/day (standard dose) until disease remission or day 15, whichever was earlier. Therapy was switched to 2 mg/kg/day in children in low-dose group not in remission by day 15. Primary outcome was days to remission, and secondary outcome being pattern of subsequent relapse(s) over 1 year. Estimating time to remission of 8 ± 2.5 days with standard-dose therapy, non-inferiority margin of 2 days, 90% power, and α-0.05, 60 patients were randomized. Of the 60 children (30 in each group) enrolled, 4 (one in low-dose group) failed remission by day 15. Time to remission was comparable between low-dose and standard-dose groups [9.0 ± 2.2 vs. 8.6 ± 2.2 days; mean difference (95% CI) 0.4 (- 0.79 to 1.59) days; p = 0.49], thus establishing non-inferiority of low dose. Median time to subsequent relapse was 86 (IQR 74.8, 97.2) and 150 (IQR 59.0, 240.9) days, in low- versus standard-dose groups, respectively (log rank p = 0.39). In follow-up, proportion of children having relapses, frequency of relapses, proportion with frequent relapse/steroid dependent (FR/SD), and cumulative corticosteroid dose taken were comparable between groups. This study shows that time to achieve remission after treatment of a relapse with low-dose prednisolone is non-inferior to that after treatment with conventional dose in children with SSNS. The proportion of children achieving remission, further course, and pattern of relapses was comparable between both groups.


Critical care health professionals' self-reported needs for wellbeing during the COVID-19 pandemic: A thematic analysis of survey responses.
Critical care healthcare professionals are a key part of any pandemic response and are at an increased risk for physical and psychological harm, yet their self-reported suggestions to ameliorate the negative effects of pandemics on their wellbeing have rarely been sought. The objective of this study was to explore and interpret themes of critical care healthcare professionals' responses to the question 'What do you think could assist your wellbeing during the COVID-19 crisis?' A descriptive study using an online survey, performed in April 2020, investigating pandemic preparedness and psychological burden during the early stages of the COVID-19 pandemic among critical care professionals was carried out. Informal snowball sampling was used. Thematic analysis of qualitative data from an open-ended survey item was informed by Braun and Clark. Eighty percent (2387/3770) of respondents completed the open-ended survey. Three themes were generated from the synthesis: adequate resourcing for the role; consistent, clear information, and prioritised communications; and the need for genuine kindness and provision of support for healthcare professional wellbeing. There is merit for considering the perceptions, concerns, and suggestions of critical care clinicians during a pandemic. Suggestions included simple measures to maintain physical and mental health, clear messaging, consistent information, trust in health and political leaders, supportive working environments, specific training, and allowances for personal circumstances. This information is important for health and political leaders and policy makers to implement strategies to reduce the burden associated with delivering care in the context of a pandemic.


Suzuki-Miyaura Cross-Coupling Reactions of Highly Fluorinated Arylboronic Esters: Catalytic Studies and Stoichiometric Model Reactions on the Transmetallation Step.
Fluorinated 4-aryl phenylalanine amino acid derivatives (aryl=2-C5 NF4 , 4-C6 H4 SF5 , 2-C6 H4 SCF3 , C6 F5 ) were obtained in Suzuki-Miyaura cross-coupling reactions of phenylalanine precursors with highly fluorinated aryl boronic acid and esters in the presence of CsF. PdII complexes that possessed phenyl alanine derived ligands, such as trans-[PdBr{4-C6 H4 CH2 CH{NHC(O)CH3 }CO2 Et}(PiPr3 )2 ], were used as catalysts. Stoichiometric model reactions indicate the intermediate generation of the boronate Cs[BF(2-C5 NF4 )(pin)] (pin=pinacolato=O2 C2 Me4 ). The transmetallation step with Cs[BF(4-C6 H4 SF5 )(pin)], [NMe4 ][BF(2-C5 NF4 )(pin)] and/or the fluorido complex trans-[PdF{4-C6 H4 CH2 C{NHC(O)CH3 }(CO2 Et)2 }(PiPr3 )2 ] was investigated. A comparison of the reactions of trans-[PdX{4-C6 H4 CH2 C{NHC(O)CH3 }(CO2 Et)2 }(PiPr3 )2 ] (X=Br, F) with 2-Bpin-C5 NF4 or [NMe4 ][BF(2-C5 NF4 )(pin)] revealed the remarkable high reactivity of the fluorido complex towards 2-BpinC5 NF4 . Low-temperature NMR studies indicated the ionic species trans-[Pd{4-C6 H4 CH2 C{NHC(O)CH3 }(CO2 Et)2 }(PiPr3 )2 ][BF(2-C5 NF4 )(pin)] to be a highly reactive intermediate.


A Systematic Review of Psychometric Properties of Knee-Related Outcome Measures Translated, Cross-Culturally Adapted, and Validated in Arabic Language.
During the previous two decades, patient-reported outcome measures (PROMs) have been well tested, and the tools were validated in different languages across the globe. This systematic review aimed to identify the knee disease-specific outcome tools in Arabic and evaluate their methodological quality of psychometric properties of the most promising tools based on the COSMIN checklist and PRISMA guidelines. Articles published in English, from the inception of databases until the date of search (10 August 2022), were included. Articles without at least one psychometric property (reliability, validity, and responsiveness) evaluation, and articles other than in the English language, were excluded from the study. The key terms ["Arabic" AND "Knee" AND ("Questionnaire" OR "Scale")] were used in three databases, i.e., PubMed, Scopus, and Web of Science (WoS) in the advanced search strategy. Key terms were either in the title or abstract for PubMed. Key words were in the topic (TS) for WoS. COSMIN (COnsensus-based Standards for the selection of health Measurement Instruments) risk of bias checklist was used to evaluate the methodological quality of psychometric properties of the Arabic knee-related outcome measures. A total of 99 articles were identified in PubMed, SCOPUS, and WoS. After passing inclusion and exclusion criteria, 20 articles describing 22 scales from five countries were included in this review. The instruments validated in the Arabic language are Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), knee injury and osteoarthritis outcome score (KOOS), knee outcome survey- activities of daily living scale (KOS-ADLS), Oxford knee score (OKS), anterior knee pain scale, osteoarthritis of knee and hip health-related quality of life (OAKHQoL) scale, Lysholm knee score (LKS), international documentation committee subjective knee form (IKDC), intermittent and constant osteoarthritis pain (ICOAP) questionnaire, Kujala patellofemoral pain scoring system (PFPSS), anterior knee pain scale (AKPS) and osteoarthritis quality of life questionnaire (OAQoL),. All were found to have good test-retest reliability (Intra Correlation Coefficient), internal consistency (Cronbach's alpha), and construct validity (Visual Analog Scale, Short Form-12, RAND-36, etc.). Of 20 instruments available to assess self-reported knee symptoms and function, 12 were validated in the Saudi Arabian population. Among them, KOS-ADLS is the best PROM to be used in various knee conditions, followed by KOOS and WOMAC. The assessed methodological quality of evidence says that the knee Arabic PROMs are reliable instruments to evaluate knee symptoms/function.


Metatranscriptomic analysis of extremely halophilic viral communities.
Hypersaline environments harbour the highest number of viruses reported for aquatic environments. In crystallizer ponds from solar salterns, haloviruses coexist with extremely halophilic Archaea and Bacteria and present a high diversity although little is known about their activity. In this work, we analyzed the viral expression in one crystallizer using a metatranscriptomic approach in which clones from a metaviromic library were immobilized in a microarray and used as probes against total mRNA extracted from the hypersaline community. This approach has two advantages: (i) it overcomes the fact that there is no straightforward, unambiguous way to extract viral mRNA from bulk mRNAs and (ii) it makes the sequencing of all mRNAs unnecessary. Transcriptomic data indicated that the halovirus assemblage was highly active at the time of sampling and the viral groups with the highest expression levels were those related to high GC content haloarchaea and Salinibacter representatives, which are minor components in the environment. Moreover, the changes in the viral expression pattern and in the numbers of free viral particles were analyzed after submitting the samples to two stress conditions: ultraviolet-radiation and dilution. Results showed that Archaea were more sensitive than Bacteria to these stress conditions. The overexpression in the predicted archaeal virus fraction raised and the total numbers of free viruses increased. Furthermore, we identified some very closely related viral clones, displaying single-nucleotide polymorphisms, which were expressed only under certain conditions. These clones could be part of very closely related virus genomes for which we propose the term 'ecoviriotypes'.


Restenosis of the Coronary Arteries: Past, Present, Future Directions.
Restenosis is a pathologic response to vascular injury, characterized by neointimal hyperplasia and progressive narrowing of a stented vessel segment. Although advances in stent design have led to a dramatic reduction in the incidence of restenosis, it continues to represent the most common cause of target lesion failure following percutaneous coronary intervention. Efforts to maximize restenosis prevention, through careful consideration of modifiable risk factors and an individualized approach, are critical, as restenosis, once established, can be particularly difficult to treat. Novel approaches are on the horizon that have the potential to alter the natural history of this stubborn disease.


Macrophages in intestinal homeostasis and inflammatory bowel disease.
Macrophages are essential for the maintenance of intestinal homeostasis, yet appear to be drivers of inflammation in the context of inflammatory bowel disease (IBD). How these peacekeepers become powerful aggressors in IBD is still unclear, but technological advances have revolutionized our understanding of many facets of their biology. In this Review, we discuss the progress made in understanding the heterogeneity of intestinal macrophages, the functions they perform in gut health and how the environment and origin can control the differentiation and longevity of these cells. We describe how these processes might change in the context of chronic inflammation and how aberrant macrophage behaviour contributes to IBD pathology, and discuss how therapeutic approaches might target dysregulated macrophages to dampen inflammation and promote mucosal healing. Finally, we set out key areas in the field of intestinal macrophage biology for which further investigation is warranted.


Clinical outcome of 500 consecutive cases undergoing Descemet's membrane endothelial keratoplasty.
To evaluate the clinical outcome of 500 consecutive cases after Descemet's membrane endothelial keratoplasty (DMEK) and the effect of technique standardization. Prospective, interventional case series at a tertiary referral center. A total of 500 eyes of 393 patients who underwent DMEK for Fuchs' endothelial corneal dystrophy, bullous keratopathy, or previous corneal transplant failure. Best-corrected visual acuity (BCVA), endothelial cell density (ECD), pachymetry, and intraoperative and postoperative complications were evaluated before and 1, 3, and 6 months after DMEK. Comparison between 2 groups (group I: cases 1-250, outcome of "early surgeries" during transition to technique standardization; group II: cases 251-500, outcome of "late surgeries" after technique standardization). At 6 months, 75% of eyes reached a BCVA of ≥20/25 (≥0.8), 41% of eyes achieved ≥20/20 (≥1.0), and 13% of eyes achieved ≥20/18 (≥1.2) (n=418) when excluding eyes with ocular comorbidities (n=57). When including all available eyes at 6 months (n=475), 66% of eyes reached a BCVA of ≥20/25 (≥0.8), and 36% of eyes achieved ≥20/20 (≥1.0). Mean ECD decreased by 37% (±18%) to 1600 (±490) cells/mm2 (n=447) at 6 months (P<0.001). Postoperative pachymetry averaged 525 (±46) μm compared with 667 (±92) μm preoperatively (P<0.001). None of these parameters differed among the 2 groups (P>0.05). (Partial) graft detachment presented in 79 eyes (15.8%), and 26 eyes (5.2%) required a secondary surgery within the first 6 months (re-bubbling in 15, secondary keratoplasty in 11). With technique standardization, the postoperative complication rate decreased from 23.2% to 10% (P<0.001) and the rate of secondary surgeries decreased from 6.8% to 3.6% (P=0.10). In comparison with earlier endothelial keratoplasty techniques, DMEK may consistently give higher visual outcomes and faster visual rehabilitation. When used for the extended spectrum of endothelial pathologies, DMEK proved feasible with a relatively low risk of complications. Technique standardization may have contributed to a lower graft detachment rate and a relatively low secondary intervention rate. As such, DMEK may become the first choice of treatment in corneal endothelial disease.


Dextran based amphiphilic nano-hybrid hydrogel system incorporated with curcumin and cerium oxide nanoparticles for wound healing.
During injury or diseased condition, wound dressing fails to properly integrate or repair the tissue and restore its function due to various factors like poor bioavailability, systemic delivery of hydrophobic drugs and elevated levels of reactive oxygen species. Here, we fabricated a novel nano-hybrid hydrogel system, based-on gelatin and oxidized dextran, embedded with nano-formulation of curcumin and cerium oxide, dispersed by physical interaction within the hydrogel. The curcumin was entrapped in amphiphilic alkylated-dextran nanoparticles to enhance its bioavailability and release at the injured site while cerium oxide nanoparticles were used without any additional processing. The hydrogel was characterized for various properties and demonstrated a controlled and prolonged drug release (∼63 % in 108 h), accelerated cell migration besides providing a highly significant antioxidant and in-vivo anti-inflammatory activity (∼39 %). The preliminary study suggests that this hybrid system can significantly promote wound healing and the potential to become an ideal wound dressing.


BM-573 inhibits the development of early atherosclerotic lesions in Apo E deficient mice by blocking TP receptors and thromboxane synthase.
Atherosclerosis is the principal cause of mortality in industrialized countries. Its development is influenced by several mediators of which thromboxane A(2) (TXA(2)) and 8-iso-PGF(2α) have recently received a lot of attention. This study aimed to investigate the effect of a dual thromboxane synthase inhibitor and thromboxane receptor antagonist (BM-573) and ASA on lesion formation in apolipoprotein E-deficient mice. The combination of ASA and BM-573 was also studied. Plasma measurements demonstrated that the treatments did not affect body weight or plasma cholesterol levels. BM-573, but not ASA, significantly decreased atherogenic lesions as demonstrated by macroscopic analysis. Both treatments alone inhibited TXB(2) synthesis but only BM-573 and the combination therapy were able to decrease firstly, plasma levels of soluble intracellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) and secondly, the expression of these proteins in the aortic root of Apo E. These results were confirmed in endothelial cell cultures derived from human saphenous vein endothelial cells (HSVECs). In these cells, BM-573 also prevented the increased mRNA expression of ICAM-1 and VCAM-1 induced by U-46619 and 8-iso-PGF(2α). Our results show that a molecule combining receptor antagonism and thromboxane synthase inhibition is more efficient in delaying atherosclerosis in Apo E(-/-) mice than sole inhibition of TXA(2) formation.


Impact of urbanization on the concentrations and distribution of organic contaminants in boreal lake sediments.
The main goal of this study was to evaluate the impacts of a middle-sized Finnish urban area on the quality of sediments in an adjacent boreal lake. We investigated the sources and distribution of organic pollutants (polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs)) in the sediments from urban stormwater traps and from Lake Vesijärvi. Grab surface sediment samples were taken from Lake Vesijärvi at various distances (25-2,000 m) from four major stormwater drainage outlets and at 15 urban stormwater traps in areas with different degrees of urbanization. These samples were analysed for 16 PAHs and 28 PCBs with gas chromatography-mass spectrometry. The concentrations of pollutants in the lake sediments were elevated in the vicinity of the urban shore (∑PAH 3-16, ∑PCB up to 0.02-0.3 mg/kg dw) and decreased as a function of distance (∑PAH 0.1-2.5, ∑PCB 0.01-0.3 mg/kg dw at a distance of more than 500 m from the shore), whereas contamination levels in suburban areas were notably lower (∑PAH 0.1-3, ∑PCB < LOQ-0.03 mg/kg dw; did not decline with distance). Possible sources and pathways of contamination were also investigated. The majority of stormwater trap sediments contained predominantly asphalt-derived PAHs due to pulverized pavement. PAHs in lake sediments were of pyrogenic origin, including the combustion of gasoline, diesel and coal. Suggested pathways of lake contamination are urban runoff discharge, boat traffic and atmospheric deposition.


From women's 'irresponsibility' to foetal 'patienthood': Obstetricians-gynaecologists' perspectives on abortion and its stigmatisation in Italy and Cataluña.
This article explores obstetricians-gynaecologists' experiences and attitudes towards abortion, based on two mixed-methods studies respectively undertaken in Italy in 2011-2012, and in Spain (Cataluña) in 2013-2015. Short questionnaires and in-depth interviews were conducted with 54 obstetricians-gynaecologists at 4 hospitals providing abortion care in Rome and Milan, and with 23 obstetricians-gynaecologists at 2 hospitals and one clinic providing abortion care in Barcelona. A medical/moral classification of abortions, from those considered 'more acceptable', both medically and morally - for severe foetal malformations - to the 'least acceptable' ones - repeated 'voluntary abortions', emerged in the discourse of most obstetricians-gynaecologists working in public hospitals, regardless of their religiosity. I argue that this is the result of the increasing medicalisation of contraception as well as of reproduction, which has reinforced the stigmatisation of 'voluntary abortion' (in case of unintended pregnancy) in a context of declining fertility rates. This contributes to explain why obstetricians-gynaecologists working in Catalan hospitals, which provide terminations only for medical reasons, unlike Italian hospitals, do not experience abortion stigma and do not object to abortion care as much as their Italian colleagues do.


Medial tibiofemoral-joint stiffness in males and females across the lifespan.
Analyzing ligament stiffness between males and females at 3 maturational stages across the lifespan may provide insight into whether changes in ligament behavior with aging may contribute to joint laxity. To compare the stiffness of the medial structures of the tibiofemoral joint and the medial collateral ligament to determine if there are differences at 3 distinct ages and between the sexes. Cross-sectional study. Laboratory. A total of 108 healthy and physically active volunteers with no previous knee surgery, no acute knee injury, and no use of exogenous hormones in the past 6 months participated. They were divided into 6 groups based on sex and age (8-10, 18-40, 50-75 years). Ligament stiffness of the tibiofemoral joint was measured with an arthrometer in 0° and 20° of tibiofemoral-joint flexion. The slope values of the force-strain line that represents stiffness of the medial tibiofemoral joint at 0° and the medial collateral ligament at 20° of flexion were obtained. When height and mass were controlled, we found a main effect (P < .001) for age group: the 8- to 10-year olds were less stiff than both the 18- to 40- and the 50- to 75-year-old groups. No effects of sex or tibiofemoral-joint position on stiffness measures were noted when height and mass were included as covariates. Prepubescent medial tibiofemoral-joint stiffness was less than postpubescent knee stiffness. Medial tibiofemoral-joint stiffness was related to height and mass after puberty in men and women.


Gerd symptoms after laparoscopic Roux-en-Y gastric bypass: an emerging scenario.
Laparoscopic Roux-en-Y gastric bypass (RYGB) is the second most performed bariatric procedure and it is considered the procedure of choice to treat patients with severe obesity and gastroesophageal reflux disease (GERD). However, some authors described the new onset or the recurrence of GERD symptoms after RYGB, and data at follow-up were scanty. In our center, we evaluated trend in weight, GERD symptoms and obesity-related comorbidities in 45 patients undergone RYGB at least 60 months before (mean follow-up 99.9 ± 22.9 months). At RYGB 51.1% patients referred preoperative GERD symptoms; among them, 47.8% showed an intraoperative hiatal hernia (HH). At medium-term follow-up mean BMI was significantly lower compared to baseline (p < 0.001). Among patients with preoperative GERD, 69.6% had GERD resolution and 30.4% reported postoperative GERD symptoms. Furthermore, 18.2% without preoperative GERD referred postoperative GERD new onset. We confirmed that RYGB as primary intervention provides satisfactory weight loss and a high percentage of GERD symptoms resolution. However, about 24.4% of patients complained of GERD symptoms at medium-term follow-up. The pathophysiology of GERD after RYGB, de novo or persistence, is not completely understood and several hypotheses could be drawn; however, further studies focusing the pathophysiology of these symptoms are needed.


A bibliometric analysis of inflammatory bowel disease and COVID-19 researches.
Patients with inflammatory bowel disease (IBD) often require immunosuppressive therapy and are hence susceptible to various opportunistic viral and bacterial infections. In this regard, many studies on IBD and COVID-19 have been conducted. However, no bibliometric analysis has been performed. This study provides a general overview of IBD and COVID-19. Publications about IBD and COVID-19 from 2020 to 2022 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using VOSviewer, CiteSpace, and HistCite. A total of 396 publications were retrieved and considered in this study. The maximum number of publications were from the United States, Italy, and England, and the contributions of these countries were significant. Kappelman ranked first in article citations. The Icahn School of Medicine at Mount Sinai and Inflammatory Bowel Diseases were the most prolific affiliation and journal, respectively. The most influential research topics were "management", "impact", "vaccination", and "receptor". The following keywords represented research frontiers: "depression", "the quality of life of IBD patients", "infliximab", "COVID-19 vaccine", and "second vaccination". Over the past 3 years, most studies on IBD and COVID-19 have focused on clinical research. In particular, topics such as "depression", "the quality of life of IBD patients", "infliximab", "COVID-19 vaccine", and "second vaccination" were noted to have received much attention recently. Future research should focus on our understanding of the immune response to COVID-19 vaccination in biologically treated patients, the psychological impact of COVID-19, IBD management guidelines, and the long-term impact of COVID-19 in IBD patients. This study will provide researchers with a better understanding of research trends on IBD during COVID-19.


Coupling of poly(ethylene glycol) to albumin under very mild conditions by activation with tresyl chloride: characterization of the conjugate by partitioning in aqueous two-phase systems.
Poly(ethylene glycol) activated with tresyl chloride has been covalently linked to albumin as a result of a 2-h incubation in 0.05 M sodium phosphate buffer, pH 7.5, containing 0.125 M sodium chloride (0.344 OSM). The coupling of poly(ethylene glycol) to albumin was demonstrated by the increase in the partition coefficient of the protein in poly(ethylene glycol)-dextran aqueous two-phase systems. A linear relationship between the log of the partition coefficient of the poly(ethylene glycol)-albumin conjugate and the degree of modification (measured as the amino groups consumed during the coupling step) has been demonstrated. Countercurrent distribution in the two-phase system showed that poly(ethylene glycol)-albumin was heterogeneous with respect to its partitioning behavior, indicating that the albumin was not uniformly modified with poly(ethylene glycol).


Real-world data in drug development strategies for orphan drugs: Tafasitamab in B-cell lymphoma, a case study for an approval based on a single-arm combination trial.
Tafasitamab (TAF) plus lenalidomide (LEN) is a novel treatment option for patients with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) who are not eligible for autologous stem cell transplantation. The initial US/EU approvals for TAF represent precedents because this is the first time that approval of a novel combination therapy was granted based on a pivotal single-arm trial (SAT). Matching real-world data (RWD) helped to disentangle the contribution of individual agents. In this review, we present the TAF development strategy, the prospective incorporation of RWD within the clinical development plan, the corresponding regulatory hurdles of this strategy, and the prior regulatory actions for other cancer drugs that previously incorporated RWD and propensity score matching in EU and US regulatory submissions. We also outline how RWD could further advance and impact orphan drug development.


Placental pathology: a systematic approach with clinical correlations.
Despite advances over the past 25 years in the monitoring of in utero fetal status, the gravid uterus remains a "black box" integrating underlying genetic risk factors, preexisting maternal disease, and injurious extrinsic events in a poorly understood way to produce an evolving state linked to pregnancy outcome. It is currently believed that many short- and long-term adverse pregnancy outcomes and even some long-term chronic diseases extending into adult life are at least in part determined by processes occurring during intrauterine life. The placenta has been described as a "diary of intrauterine life" and has the potential to illuminate many aspects of these processes. Unfortunately a systematic and objective catalog of placental abnormalities has never been agreed upon. This report outlines a simple conceptual framework separating placental patterns of injury and maladaptation into three categories of lesions affecting the maternal and fetal vasculature (maldevelopment, obstruction, and disruption) and two categories of inflammatory lesions (infectious and idiopathic). Data are presented supporting the importance of these processes for an understanding of preterm delivery, intrauterine growth restriction, hypoxic-ischemic injury, and recurrent pregnancy loss.


Quantitative assessment of the association between HDMX polymorphism and sarcoma.
To investigate the effects of the HDMX polymorphism on sarcoma risk. Relevant studies were identified by searching the PubMed, Embase, and Web of Science databases. Data were extracted by two independent investigators. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using a fixed-effects model to assess the association between the HDMX polymorphism and sarcoma risk. We also conducted heterogeneity test, sensitivity analysis, and publication bias test. A meta-analysis of four published case-control studies involving 1,115 subjects (379 cases and 736 controls) showed no statistical association between the HDMX polymorphism and sarcoma risk (ORTT vs. GG 0.88, 95 % CI 0.68-1.14, P heterogeneity 0.819; ORTT + TG vs. GG 0.95, 95 % CI 0.79-1.15, P heterogeneity 0.937; ORTT vs. TG + GG 0.82, 95 % CI 0.65-1.04, P heterogeneity 0.589; ORT allele vs. G allele 0.91, 95 % CI 0.79-1.05, P heterogeneity 0.727; ORTG vs. GG 0.95, 95 % CI 0.74-1.22, P heterogeneity = 0.869). This null result did not alter when data were stratified according to ethnicity. Our meta-analysis indicates that the HDMX polymorphism is unlikely to contribute to individual susceptibility to sarcoma.


The high mobility group box 1 protein of Sciaenops ocellatus is a secreted cytokine that stimulates macrophage activation.
High mobility group box 1 protein (HMGB1) is a chromatin-associated nonhistone protein that is involved in nucleosome formation and transcriptional regulation. In addition, HMGB1 is also known as an extracellular cytokine that triggers inflammation and immune responses. HMGB1-like sequences have been identified in a number of fish species, however, the function of piscine HMGB1 remains uninvestigated. In this study, we reported the identification and analysis of SoHMGB1, an HMGB1 homologue from red drum (Sciaenops ocellatus). SoHMGB1 is 206 residues in length and contains two basic HMG boxes and a highly acidic C-terminal domain. SoHMGB1 shares 71-87% overall sequence identities with the HMGB1 counterparts from human, rat, and several fish species. Quantitative real time RT-PCR analysis showed that constitutive SoHMGB1 expression was detected in various tissues, with the lowest and highest levels found in kidney and muscle respectively. Bacterial challenge upregulated SoHMGB1 expression in head kidney (HK) and HK macrophages and induced extracellular secretion of SoHMGB1 by the activated macrophages. Recombinant SoHMGB1 (rSoHMGB1) purified from yeast exhibited no direct antimicrobial effect but was significantly stimulatory on the proliferation, activation, and bactericidal activity of HK macrophages. Taken together, these results indicate for the first time that a fish HMGB1, SoHMGB1, can function as a secreted cytokine in the event of bacterial infection and promote innate defense through the activation of macrophages.


Type I Diabetes is the Main Cost Driver in Autoimmune Polyendocrinopathy.
Autoimmune polyendocrinopathy (AP), a chronic complex orphan disease, encompasses at least two autoimmune-induced endocrine diseases. To estimate for the first time total, indirect and direct costs for patients with AP, as well as cost drivers. Cross-sectional cost of illness study. Academic tertiary referral center for AP. 146 consecutive, unselected AP patients. Interviews pertaining to patients' socioeconomic situation covered a recall period of 12 months. Both the human capital (HCA) and the friction cost approaches (FCAs) were applied as estimation methods. Direct and indirect annual costs, and sick leave and medication costs. AP markedly impacts healthcare expenses. Mean overall costs of AP in Germany ranged from €5 971 090 to €29 848 187 per year (HCA). Mean indirect costs ranged from €3 388 284 to €16 937 298 per year (HCA) while mean direct costs ranged from €2 582 247 to €12 908 095/year. Mean direct costs per year were €1851 in AP patients with type 1 diabetes (T1D, 76%) and €671 without T1D, which amounts to additional direct costs of €1209 for T1D when adjusting for concomitant autoimmune disease (95% CI = €1026-1393, P < 0.0001). Sick leave cost estimates for AP patients with T1D exceeded those without T1D by 70% (FCA) and 43% (HCA), respectively. In multiple regression analyses, T1D predicted total and direct costs, medication costs and costs for diabetic devices (all P < 0.001). Overall, AP patients with T1D were 54% (FCA) more expensive than those without T1D. Public health socioeconomic relevance of AP was demonstrated, with T1D as main cost driver.


Staged reconstruction of hemimaxillectomy defect: Application of buccal fat pad flap, iliac bone graft and implant-supported dental prostheses.
In order to achieve a fixed implant-supported prosthesis in a posthemimaxilectomy patient, ideal soft and hard tissue rehabilitation is necessary. Here, we present a staged approach for soft tissue reconstruction with local flaps followed by anterior iliac crest bone graft which resulted in a predictable and satisfactory outcome.


Serum proteomic analysis reveals potential serum biomarkers for occupational medicamentosa-like dermatitis caused by trichloroethylene.
Trichloroethylene (TCE) is an industrial solvent with widespread occupational exposure and also a major environmental contaminant. Occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) is an autoimmune disease and it has become one major hazard in China. In this study, sera from 3 healthy controls and 3 OMLDT patients at different disease stages were used for a screening study by 2D-DIGE and MALDI-TOF-MS/MS. Eight proteins including transthyretin (TTR), retinol binding protein 4 (RBP4), haptoglobin, clusterin, serum amyloid A protein (SAA), apolipoprotein A-I, apolipoprotein C-III and apolipoprotein C-II were found to be significantly altered among the healthy, acute-stage, healing-stage and healed-stage groups. Specifically, the altered expression of TTR, RBP4 and haptoglobin were further validated by Western blot analysis and ELISA. Our data not only suggested that TTR, RBP4 and haptoglobin could serve as potential serum biomarkers of OMLDT, but also indicated that measurement of TTR, RBP4 and haptoglobin or their combination could help aid in the diagnosis, monitoring the progression and therapy of the disease.


Green non-conventional techniques for the extraction of polyphenols from agricultural food by-products: A review.
Food processing industry is accompanied with the generation of a great production of wastes and by-products exceptionally rich in bioactive compounds (especially phenolics), with antioxidant activity. The recovery of these health molecules constitutes a key point for the valorization of by-products, with the possibility of creating new ingredients to be used for the formulation of food and cosmetic products. One of the main limitations to reuse by-products is linked to the high cost to obtain bioactive compounds, consequently in order to exploit these resources commercially valuable it is necessary to develop innovative, economic and environmentally friendly extraction strategies. These extraction methods should be able to reduce petroleum solvents, energy consumption and chemical wastes, protecting both environment and consumers and ensuring safe and high-quality final products. The purpose of this review is to summarize current knowledge and applications of the new extraction techniques such as supercritical fluid extraction, pressurized liquid extraction, ultrasound assisted extraction applied to polyphenols extraction from agricultural food by-products. Particular attention has been paid to theoretical background, highlighting mechanisms and safety precautions. Authors concluded that relevant results of these techniques represent an opportunity to industrial scale-up, improving the extraction yields, minimizing time, costs and environmental impact.


Determinants of adherence to oral hygiene prophylaxis guidelines in patients with previous infective endocarditis.
Infective endocarditis (IE) is characterized by low incidence but high mortality. Patients with a history of IE are at highest risk. Adherence to prophylaxis recommendations is poor. We sought to identify determinants of adherence to oral hygiene guidelines on IE prophylaxis in patients with a history of IE. Using data from the cross-sectional, single-centre POST-IMAGE study, we analysed demographic, medical and psychosocial factors. We defined patients as adherent to prophylaxis if they declared going to the dentist at least annually and brushing their teeth at least twice a day. Depression, cognitive status and quality of life were assessed using validated scales. Of 100 patients enrolled, 98 completed the self-questionnaires. Among these, 40 (40.8%) were categorized as adherent to prophylaxis guidelines, and were less likely to be smokers (5.1% vs. 25.0%; P=0.02) or have symptoms of depression (36.6% vs. 70.8%; P<0.01) or cognitive decline (0% vs. 15.5%; P=0.05). Conversely, they had higher rates of: valvular surgery since the index IE episode (17.5% vs. 3.4%; P=0.04), searching for information on IE (61.1% vs. 46.3%, P=0.05), and considering themselves as adherent to IE prophylaxis (58.3% vs. 32.1%; P=0.03). Tooth brushing, dental visits and antibiotic prophylaxis were correctly identified as measures to prevent IE recurrence in 87.7%, 90.8% and 92.8% of patients, respectively, and did not differ according to adherence to oral hygiene guidelines. Self-reported adherence to secondary oral hygiene guidelines on IE prophylaxis is low. Adherence is unrelated to most patient characteristics, but to depression and cognitive impairment. Poor adherence appears related more to a lack of implementation rather than insufficient knowledge. Assessment of depression may be considered in patients with IE.


Pyrazolopyridine inhibitors of B-RafV600E. Part 2: structure-activity relationships.
Structure-activity relationships around a novel series of B-Raf(V600E) inhibitors are reported. The enzymatic and cellular potencies of inhibitors derived from two related hinge-binding groups were compared and3-methoxypyrazolopyridine proved to be superior. The 3-alkoxy group of lead B-Raf(V600E) inhibitor 1 was extended and minimally affected potency. The propyl sulfonamide tail of compound 1, which occupies the small lipophilic pocket formed by an outward shift of the αC-helix, was expanded to a series of arylsulfonamides. X-ray crystallography revealed that this lipophilic pocket unexpectedly enlarges to accommodate the bulkier aryl group.


Front-line education by infection preventionists helps reduce Clostridioides difficile infections.
When implementing the latest innovations to reduce health care-associated infections, it is important not to overlook basic infection prevention principles such as hand hygiene, isolation precautions, use of personal protective equipment, and cleaning and low-level disinfection. Like many facilities, we implemented a multifaceted approach to reduce hospital-onset Clostridioides difficile infections. In this paper, we share simple tools that we found helpful in improving infection prevention practices by addressing knowledge gaps among staff, visitors, and patients.


Membrane stretch accelerates activation and slow inactivation in Shaker channels with S3-S4 linker deletions.
At low P(open)(V) Shaker exhibits pronounced stretch-activation. Possible explanations for Shaker's sensitivity to tension include 1) Shaker channels are sufficiently distensible that stretch produces novel channel states and 2) Shaker channels expand in the plane of the membrane during voltage gating. For channels expressed in oocytes, we compared effects of patch stretch on Shaker and mutants that retain their voltage-gating ability but activate sluggishly because all or most of the S3-S4 linker has been deleted. Deletants had 10, 5, or 0 amino acid (aa) linkers, whereas wild-type is 31 aa. In deletants, though activation is exceptionally slow, slow inactivation is exceptionally quick; the resulting kinetic match was a bonus that allowed effects of stretch to be followed simultaneously in both processes. With the intact linker, an approximately 3 orders of magnitude mismatch in the two processes makes this impracticable. Standard stretch stimuli increased the rates and extent of activation by about the same degree in wild type and deletants, with effects especially pronounced near the foot of G(V). In deletants (where slow inactivation is strongly coupled to activation) stretch also accelerated slow inactivation. Maximum conductances were unaffected by stretch in all variants. In ramp clamp dose experiments, near-lytic patch stretch acted, for all variants, like a approximately 10 mV hyperpolarizing shift. These results suggested that, whether basal rates were high (wild type) or low (deletants), stretch acted by facilitating voltage-dependent activation. Channel activity was therefore simulated with/without "tension," tension being simulated via rate changes at voltage-dependent closed-closed transitions that might involve in-plane expansion (explanation 2). Simulated Delta P(open) arising from approximately 2 kT of "mechanical gating energy" mimicked experimental effects seen with comfortably sub-lytic stretch.


Disaster response in a pediatric field hospital: lessons learned in Haiti.
This study outlines the evolution of a pediatric field hospital after the January 2010 Haiti earthquake. Project Medishare set up a field hospital in Port-au-Prince 48 hours after the event. Our institution staffed the pediatric component for 45 days, with sequential deployment of 9 volunteer medical teams. Evolving facility and manpower requirements and changing patient demographics over time were evaluated. Delegations consisted of surgeons, pediatricians, nurses, operating room (OR) personnel, physical therapists, pharmacists, and support staff. Primary goals involved creation of a child-specific ward, pediatric OR, and a wound care center. Major inpatient demographic changes occurred as time from the disaster elapsed. Initial census showed that 93% of the patients were surgical admissions with 40% undergoing operations, mostly fracture and wound care, over the first week. Eight weeks later, medical illnesses accounted for 70% of inpatients, whereas OR volume dropped by more than 50%. A second trend involved increasing acuity of care. Initially, children were admitted for serious or limb-threatening, but usually not life-threatening, injuries. Within 2 months, one third of the patients were housed in the developing NICU/PICU; and only 12% were admitted for injuries related to the earthquake. This change in patient needs led to alterations in facility requirements and in staffing and leadership needs. A disaster involving significant casualties in a populated area demands the rapid development of a field facility with pediatric personnel. Requirements for equipment, manpower, medical records, and systems addressing volunteer stress and ethical dilemmas can be anticipated.


Optimal Symmetric Multimodal Templates and Concatenated Random Forests for Supervised Brain Tumor Segmentation (Simplified) with ANTsR.
Segmenting and quantifying gliomas from MRI is an important task for diagnosis, planning intervention, and for tracking tumor changes over time. However, this task is complicated by the lack of prior knowledge concerning tumor location, spatial extent, shape, possible displacement of normal tissue, and intensity signature. To accommodate such complications, we introduce a framework for supervised segmentation based on multiple modality intensity, geometry, and asymmetry feature sets. These features drive a supervised whole-brain and tumor segmentation approach based on random forest-derived probabilities. The asymmetry-related features (based on optimal symmetric multimodal templates) demonstrate excellent discriminative properties within this framework. We also gain performance by generating probability maps from random forest models and using these maps for a refining Markov random field regularized probabilistic segmentation. This strategy allows us to interface the supervised learning capabilities of the random forest model with regularized probabilistic segmentation using the recently developed ANTsR package--a comprehensive statistical and visualization interface between the popular Advanced Normalization Tools (ANTs) and the R statistical project. The reported algorithmic framework was the top-performing entry in the MICCAI 2013 Multimodal Brain Tumor Segmentation challenge. The challenge data were widely varying consisting of both high-grade and low-grade glioma tumor four-modality MRI from five different institutions. Average Dice overlap measures for the final algorithmic assessment were 0.87, 0.78, and 0.74 for "complete", "core", and "enhanced" tumor components, respectively.


Influence of different surfactants on the separation of von Willebrand factor multimers by use of agarose gel electrophoresis and semi dry blotting technology.
The separation of vWF-multimers by use of sodium dodecyl sulfate (SDS) agarose gel electrophoresis and semi dry blotting instead of tank blotting procedure has been studied. We could demonstrate, that multimers in the range of highest molecular weights could not be visualized using this technique. Therefore we have investigated the influence of different types of anionic surfactants on the separation of vWF-multimers and could show that the hydrophilic/lipophilic balance (HLB) is an important value to characterize the capacity of a surfactant to separate vWF-multimers. The best separation quality was achieved with sodium dodecyl benzene sulfonate (SDBS). This surfactant is a superior alternative to SDS in separating vWF-multimers of the highest molecular weights.


A deep learning algorithm for classification of oral lichen planus lesions from photographic images: A retrospective study.
Deep learning methods have recently been applied for the processing of medical images, and they have shown promise in a variety of applications. This study aimed to develop a deep learning approach for identifying oral lichen planus lesions using photographic images. Anonymous retrospective photographic images of buccal mucosa with 65 healthy and 72 oral lichen planus lesions were identified using the CranioCatch program (CranioCatch, Eskişehir, Turkey). All images were re-checked and verified by Oral Medicine and Maxillofacial Radiology experts. This data set was divided into training (n = 51; n = 58), verification (n = 7; n = 7), and test (n = 7; n = 7) sets for healthy mucosa and mucosa with the oral lichen planus lesion, respectively. In the study, an artificial intelligence model was developed using Google Inception V3 architecture implemented with Tensorflow, which is a deep learning approach. AI deep learning model provided the classification of all test images for both healthy and diseased mucosa with a 100% success rate. In the healthcare business, AI offers a wide range of uses and applications. The increased effort increased complexity of the job, and probable doctor fatigue may jeopardize diagnostic abilities and results. Artificial intelligence (AI) components in imaging equipment would lessen this effort and increase efficiency. They can also detect oral lesions and have access to more data than their human counterparts. Our preliminary findings show that deep learning has the potential to handle this significant challenge.


Effect of an antiandrogen on the lymphoid system.
A side-effect of the administration of cyproterone acetate, an antiandrogenic steroid, to newborn, juvenile or adult male mice (in doses comparable to those used clinically) was found in a marked reduction of the white pulp of the spleen and reduced weight or even absence of the thymus.


Efficacy of bleb-independent penetrating canaloplasty in primary angle-closure glaucoma: one-year results.
To report the efficacy and safety of bleb-independent penetrating canaloplasty in the management of primary angle-closure glaucoma (PACG). This single-centre prospective interventional case series enrolled 57 eyes from 53 PACG patients with medically uncontrolled intraocular pressure (IOP) and peripheral anterior synechiae of over 270°. Penetrating canaloplasty, mainly consisted of tensioning suture-aided Schlemm's canal dilation and a trabeculectomy, was performed to create a direct communication between the anterior chamber and the Schlemm's canal. Postoperative IOP, number of glaucoma medications and procedure-related complications were evaluated. Rate of success was defined as IOP ≤ 21, ≤18 and ≤15 mmHg, and a ≥30% IOP reduction without (complete) or with/without (qualified) IOP-lowering medications. A total of 45 eyes had 360° catheterization successfully completed. The mean preoperative IOP was 33.9 ± 11.7 mmHg (range, 13-59.6 mmHg), on 3.2 ± 0.8 glaucoma medications (range 2-5), which was decreased to 15.4 ± 3.7 mmHg (range, 8.6-22.5) and 0.2 ± 0.6 (range, 0-3) medications at 6 months and 14.8 ± 3.5 mmHg (range, 9-24) and 0.1 ± 0.3 (range, 0-1) medications at 12 months postoperatively. Complete success at 12 months were achieved in 78.9% (95% CI: 0.65-0.93), 71.1% (0.56-0.86) and 50.0% (0.33-0.67) eyes at IOP ≤ 21, ≤18 and ≤15 mmHg, respectively. Transient IOP elevation (>30 mmHg, 26.7%) and hyphema (11.1%) were the most common early surgical complications. Penetrating canaloplasty in PACG appeared to have good efficacy and safety profiles in this pilot study. Further studies are justified.


Competition by meperidine for the organic cation renal excretory system.
Renal tubular excretory transport of meperidine was studied using the Sperber preparation in chickens. When urine samples from infused and uninfused kidneys were analyzed for meperidine by gas chromatography, meperidine was always present in greater amounts in the urine from the infused kidney, demonstrating active tubular excretion. Meperidine at an infusion rate of 1 mumole/min, also inhibited the excretion of the organic cations choline and acetylcholine, indicating occupation of the renal organic cation excretory system in the chicken.


N-myc gene is amplified in alveolar rhabdomyosarcomas (RMS) but not in embryonal RMS.
DNA from 13 (6 alveolar and 7 embryonal) childhood rhabdomyosarcomas (RMS) was examined to determine the incidence and prognostic relevance of N- and c-myc genes. Southern analysis showed 5- to 20-fold amplification of N-myc gene in 4 of 6 alveolar but in none of 7 embryonal RMS (p less than 0.04; Fisher's exact test). The number of children who died with multiple- and single-copy N-myc gene was 4/4 and 5/9 respectively (p greater than 0.05; Chi-squared test). There was no statistically significant correlation between N-myc amplification and age, gender, site, stage or survival time. There was no amplification or gross rearrangement of c-myc in any of the 13 RMS.


Heart rate variability and oxygen reserve index during cardiorespiratory events in patients undergoing ophthalmic arterial chemotherapy: a prospective observational study.
Unexpected cardiorespiratory compromise has been reported during ophthalmic arterial chemotherapy in pediatric patients with retinoblastoma. Although the underlying mechanisms remain unclear, autonomic responses are presumed to contribute to these events. We hypothesized that periprocedural heart rate variability would differ between patients with and without events. Between April 2018 and September 2019, 38 patients (age under 7 years) were included. Heart rate variability was analyzed using electrocardiogram, and oxygen reserve index was also monitored. Cardiorespiratory events were defined as > 30% changes in blood pressure or heart rate, > 20% changes in end-tidal carbon dioxide, > 40% changes in peak inspiratory pressure, or pulse oxygen saturation < 90% during ophthalmic artery catheterization. Heart rate variability and oxygen reserve index were compared between patients with and without cardiorespiratory events. Cardiorespiratory events occurred in 13/38 (34%) patients. During the events, end-tidal carbon dioxide was significantly lower (median difference [95% CI], - 2 [- 4 to - 1] mmHg, p = 0.006) and the maximum peak inspiratory pressure was higher (30 [25-37] vs. 15 [14-16] hPa, p < 0.001), compared to patients without events. Standard deviation of normal-to-normal R-R interval, total power, and very low-frequency power domain increased during selection of the ophthalmic artery in patients with events (all adjusted p < 0.0001), without predominancy of specific autonomic nervous alterations. Oxygen reserve index was significantly lower in patients with events than those without throughout the procedure (mean difference [95% CI], - 0.19 [- 0.32 to - 0.06], p = 0.005). Enhanced compensatory autonomic regulation without specific autonomic predominancy, and reduced oxygen reserve index was observed in patients with cardiorespiratory events than in patients without events.


Transfer of exposure therapy effects to a threat context not considered during treatment in patients with panic disorder and agoraphobia: Implications for potential mechanisms of change.
Further developments of exposure-based therapy (EBT) require more knowledge about transfer of treatment to non-trained everyday contexts. However, little is known about transfer effects of EBT. Using a standardized EBT protocol in 275 patients with panic disorder and agoraphobia we investigated the transfer of EBT to a highly standardized context during a Behavioral Avoidance Test (BAT; being entrapped in a small and dark test chamber) and not part of the exposure sessions. Patients of a treatment group underwent the BATs before treatment (t1), after a preparatory treatment phase (t2), and after an agoraphobic exposure phase (t3) and were compared with wait-list control patients, who repeated BAT assessments across the same time period. We found stronger reductions in avoidance behavior, reported fear, and autonomic arousal during the BAT from t1 to t3 in the treatment group patients who were anxious during t1 relative to the anxious but untreated patients. Fear reduction was related to treatment outcome indicating the contribution of transfer effects to successful EBT. Interestingly, reduction varied for different fear response systems suggesting different processes to may be involved in transfer effects. Importantly, final BAT assessment still evoked residual fear in the treatment group as compared to BAT non-anxious control patients, suggesting limited transfer effects - one possible reason for the return of symptoms in new situations.


Multi-level selection for hygienic behaviour in honeybees.
Disease is one of the main factors driving both natural and artificial selection. It is a particularly important and increasing threat to the managed honeybee colonies, which are vital in crop pollination. Artificial selection for disease-resistant honeybee genotypes has previously only been carried out at the colony-level, that is, by using queens or males reared from colonies that show resistance. However, honeybee queens mate with many males and so each colony consists of multiple patrilines that will vary in heritable traits, such as disease resistance. Here, we investigate whether response to artificial selection for a key resistance mechanism, hygienic behaviour, can be improved using multi-level selection, that is, by selecting not only among colonies as normal but also among patrilines within colonies. Highly hygienic colonies were identified (between-colony selection), and the specific patrilines within them responsible for most hygienic behaviour were determined using observation hives. Queens reared from these hygienic patrilines (within-colony selection) were identified using DNA microsatellite analysis of a wing-tip tissue sample and then mated to drones from a third highly hygienic colony. The resulting colonies headed by queens from hygienic patrilines showed approximately double the level of hygienic behaviour of colonies headed by sister queens from non-hygienic patrilines. The results show that multi-level selection can significantly improve the success of honeybee breeding programs.


3-MHPG as a non-predictor of antidepressant response to imipramine and electroconvulsive therapy.
The urinary excretion of 3-methoxy, 4-hydroxyphenyl-glycol, (3-MHPG) was measured in 20 unipolar depressed patients before treatment with imipramine and electroconvulsive therapy (ECT) to investigate the relationship between pretreatment urinary excretion of 3-MHPG and clinical response. There was no difference in 3-MHPG excretion for depressed patients and controls. There was no significant difference between the mean percentage reduction of Hamilton Depression Rating Scale Scores in "low" and "high" excretors of 3-MHPG in the imipramine and ECT group of patients after four weeks of treatment.


Structural and anti-inflammatory characterization of a novel neutral polysaccharide from North American ginseng (Panax quinquefolius).
Neutral polysaccharides are one of the active components in the American ginseng roots. Recently, the studies about American ginseng polysaccharides are mainly centered on acidic polysaccharides, while there is relatively limited research that explores neutral polysaccharides. In this study a novel neutral polysaccharide (PPQN) was isolated from American ginseng roots and its structure and anti-inflammatory activity were investigated. The average molecular weight (Mw) of PPQN was 3.1 kDa. Monosaccharide components' analysis indicated that PPQN was composed of glucose (Glc) and galactose (Gal) in a molar ratio of 1:1.15. Secretions of nitric oxide (NO), TNF-α, IL-6, and IL-1β after lipopolysaccharide (LPS) stimulation were detected in PPQN pre-treatment RAW264.7 macrophages. PPQN (150 μg/mL) exhibited more effective inhibition of TNF-α, IL-1β, and IL-6 secretions, followed by NO production with respective values of 40.5%, 41.1%, 34.4%, and 11.1% suppression. These results indicated that PPQN may have therapeutic implications in treatment of inflammation and inflammatory-related diseases.


Striatal D2 receptor binding as a marker of prognosis and outcome in untreated first-episode psychosis.
In a preliminary 123I-IBZM SPECT study in first-episode psychosis, a relationship between striatal dopaminergic D2 receptor (D2R) binding and premorbid adjustment was suggested. These results were replicated in the present study (n = 18), and D2R binding at diagnosis predicted a high probability for schizophrenia outcome by 2-year follow-up. The present findings contribute to the evidence of abnormal D2R binding in schizophrenia and suggest that SPECT might be useful for outcome prediction in first-episode psychosis.


Adolescents and the internet.
The interactive, multimedia nature of the Internet makes it a potentially invaluable resource for adolescents. These same characteristics also mean that the Internet could be a potentially hazardous medium for certain members of this age group. Although the Internet allows adolescents access to an unprecedented amount of content in an endless number of areas, it also allows them access to content that many parents and caregivers find particularly objectionable. This article addresses several primary benefits and potential hazards associated with adolescent Internet use. It describes general trends in adolescent Internet use and considers how the medium allows individuals to extend their social networks and create new ones. Several ideas for maximizing the potential benefits and minimizing any potential harms are presented.


Hydroxylated single-walled carbon nanotube inhibits β2m21-31 fibrillization and disrupts pre-formed proto-fibrils.
Pathological aggregation of amyloid polypeptides is associated with numerous degenerative diseases. Preventing aggregation and clearing amyloid deposits are considered as promising strategies against amyloidosis. With the capacity of crossing the blood-brain barrier and good biocompatibility, the hydroxylated single-walled carbon nanotube (SWCNT-OH) has been shown with excellent anti-amyloid properties. Here, we systematically studied the SWCNT-OH effects on the fibrillization of the β2m21-31 peptides utilizing all-atom discrete molecular dynamics (DMD) simulation. Our results demonstrated the isolated β2m21-31 peptides first nucleated into unstructured oligomers followed by coil-to-sheet conformational conversions in oligomers with at least six peptides. The elongation and lateral surfaces of the preformed β-sheet could catalyze the other unstructured monomers and small oligomers converted into β-sheet formations via dock-lock fibril growth and secondary nucleation processes. Eventually, the β2m21-31 peptides would self-assemble into well-ordered cross-β structures. Regardless of isolated monomers or well-defined cross-β assemblies, the β2m21-31 would attach on the surfaces of SWCNT-OH adopting unstructured formations indicating the SWCNT-OH not only inhibited the fibrillization of β2m21-31 but also destroyed pre-formed proto-fibrils. Overall, our study displays a complete picture of the fibrillization mechanism of β2m21-31 and the amyloid inhibitory mechanism of SWCNT-OH, offering new insight into the de-novo design of anti-amyloid inhibitors.


Infant aspiration and associated signs on clinical feeding evaluation.
Few studies have examined clinical signs of aspiration in infants <51 weeks post-menstrual age (PMA) for whom the laryngeal cough reflex is not fully developed. This retrospective study explored 1) the association between signs of aspiration on a clinical feeding evaluation (CFE) and/or comorbid conditions with aspiration (silent or overt) on a modified barium swallow study (MBS) for infants in this age range, 2) the association between lower respiratory infection (LRI) and aspiration on MBS, and 3) the sensitivity and specificity of detecting aspiration according to signs on CFE and the evaluating speech-language pathologist's (SLP) years of experience. A retrospective review of charts of patients with MBS completed January 1, 2012-December 31, 2014 was performed. Patients were included if they were <51-weeks PMA at the time of MBS and had a CFE conducted no more than seven days prior to the MBS. Patient age, comorbidities, and MBS and CFE details were collected. The impact of CFE findings, patient age, comorbid syndromes/associations, and aerodigestive diagnoses on the odds of demonstrating silent aspiration (SA) or overt aspiration during MBS with thin liquids was determined using logistic regression, and the sensitivity and specificity of CFE for identifying SA was calculated. Results from 114 patients indicated that 46 (40 %) of the infants had SA and nine (8 %) had overt aspiration on MBS. Notable signs on CFEs were cough (36 %), oxygen desaturations (33 %), and chest congestion (32 %). On multiple regression analysis there was increased odds of SA on MBS with at least one clinical sign on CFE (OR: 24.3, p = 0.02), chronic lung disease, (OR: 18.2, p = 0.01), and airway abnormalities (OR: 2.94, p = 0.01). Cough on CFE was associated with increased odds of overt aspiration on MBS (OR: 5.69, p = 0.04). Neither SA nor overt aspiration were significantly associated with LRI. Sensitivity and specificity of CFE for correctly identifying the presence of SA were 98 % and 15 %, respectively; experience of the SLP was not a contributing factor. Further study is required to determine if specific signs on CFE are predictive of aspiration.


Risk of Accidents or Chronic Disorders From Improper Use of Mobile Phones: A Systematic Review and Meta-analysis.
Mobile phone use has brought convenience, but the long or improper use of mobile phones can cause harm to the human body. We aimed to assess the impact of improper mobile phone use on the risks of accidents and chronic disorders. We systematically searched in PubMed, EMBASE, Cochrane, and Web of Science databases for studies published prior to April 5, 2019; relevant reviews were also searched to identify additional studies. A random-effects model was used to calculate the overall pooled estimates. Mobile phone users had a higher risk of accidents (relative risk [RR] 1.37, 95% CI 1.22 to 1.55). Long-term use of mobile phones increased accident risk relative to nonuse or short-term use (RR 2.10, 95% CI 1.63 to 2.70). Compared with nonuse, mobile phone use resulted in a higher risk for neoplasms (RR 1.07, 95% CI 1.01 to 1.14), eye diseases (RR 2.03, 95% CI 1.27 to 3.23), mental health disorders (RR 1.16, 95% CI 1.02 to 1.32), and headaches (RR 1.25, 95% CI 1.18 to 1.32); the pooled risk of other chronic disorders was 1.20 (95% CI 0.90 to 1.59). Subgroup analyses also confirmed the increased risk of accidents and chronic disorders. Improper use of mobile phones can harm the human body. While enjoying the convenience brought by mobile phones, people have to use mobile phones properly and reasonably.


Human Milk Oligosaccharide 2'-Fucosyllactose Modulates Local Viral Immune Defense by Supporting the Regulatory Functions of Intestinal Epithelial and Immune Cells.
Human milk contains bioactive components that provide protection against viral infections in early life. In particular, intestinal epithelial cells (IEC) have key regulatory roles in the prevention of enteric viral infections. Here we established an in vitro model to study the modulation of host responses against enteric viruses mimicked by poly I:C (pIC). The effects of 2'-fucosyllactose (2'FL), abundantly present in human milk, were studied on IEC and/or innate immune cells, and the subsequent functional response of the adaptive immune cells. IEC were pre-incubated with 2'FL and stimulated with naked or Lyovec™-complexed pIC (LV-pIC). Additionally, monocyte-derived dendritic cells (moDC) alone or in co-culture with IEC were stimulated with LV-pIC. Then, conditioned-moDC were co-cultured with naïve CD4+ T helper (Th)-cells. IEC stimulation with naked or LV-pIC promoted pro-inflammatory IL-8, CCL20, GROα and CXCL10 cytokine secretion. However, only exposure to LV-pIC additionally induced IFNβ, IFNλ1 and CCL5 secretion. Pre-incubation with 2'FL further increased pIC induced CCL20 secretion and LV-pIC induced CXCL10 secretion. LV-pIC-exposed IEC/moDC and moDC cultures showed increased secretion of IL-8, GROα, IFNλ1 and CXCL10, and in the presence of 2'FL galectin-4 and -9 were increased. The LV-pIC-exposed moDC showed a more pronounced secretion of CCL20, CXCL10 and CCL5. The moDC from IEC/moDC cultures did not drive T-cell development in moDC/T-cell cultures, while moDC directly exposed to LV-pIC secreted Th1 driving IL-12p70 and promoted IFNγ secretion by Th-cells. Hereby, a novel intestinal model was established to study mucosal host-defense upon a viral trigger. IEC may support intestinal homeostasis, regulating local viral defense which may be modulated by 2'FL. These results provide insights regarding the protective capacity of human milk components in early life.


Synthesis and biological evaluation of novel 2,4-disubstituted-1,3-thiazoles as anti-Candida spp. agents.
A new series of [4-(4'-substituted-phenyl)thiazol-2-yl]hydrazine derivatives were synthesized in good yield (86-99%) and characterized by elemental analysis, IR, (1)H NMR, and mass spectral studies. The compounds were assayed for their in vitro broad-spectrum antifungal activity, compared to clotrimazole and fluconazole, against 20 clinical isolates of pathogenic Candida spp., representing five different species. The results showed that the presence of heterocyclic or bicyclic rings on hydrazone moiety in position C2 of thiazole revealed a promising selective inhibitory activity especially against Candida albicans and Candida glabrata.


Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders.
Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) are autosomal dominant developmental disorders. NS and NSML are caused by abnormalities in genes that encode proteins related to the RAS-MAPK pathway, including PTPN11, RAF1, BRAF, and MAP2K. In this study, we diagnosed ten NS or NSML patients via targeted sequencing or whole exome sequencing (TS/WES). TS/WES was performed to identify mutations in ten Chinese patients who exhibited the following manifestations: potential facial dysmorphisms, short stature, congenital heart defects, and developmental delay. Sanger sequencing was used to confirm the suspected pathological variants in the patients and their family members. TS/WES revealed three mutations in the PTPN11 gene, three mutations in RAF1 gene, and four mutations in BRAF gene in the NS and NSML patients who were previously diagnosed based on the abovementioned clinical features. All the identified mutations were determined to be de novo mutations. However, two patients who carried the same mutation in the RAF1 gene presented different clinical features. One patient with multiple lentigines was diagnosed with NSML, while the other patient without lentigines was diagnosed with NS. In addition, a patient who carried a hotspot mutation in the BRAF gene was diagnosed with NS instead of cardiofaciocutaneous syndrome (CFCS). TS/WES has emerged as a useful tool for definitive diagnosis and accurate genetic counseling of atypical cases. In this study, we analyzed ten Chinese patients diagnosed with NS and related disorders and identified their correspondingPTPN11, RAF1, and BRAF mutations. Among the target genes, BRAF showed the same degree of correlation with NS incidence as that of PTPN11 or RAF1.


Breast-feeding During Pregnancy and the Risk of Miscarriage.
Breast-feeding rates and durations have been increasing among U.S. women in recent decades. As a result, women may be more likely to practice breast-feeding during pregnancy (BDP), which has been hypothesized to increase the risk of miscarriage, yet there has been little research into the issue. Data on 10,661 pregnancies from several waves of the National Survey of Family Growth, covering the years 2002-2015, were used to calculate unadjusted miscarriage rates according to BDP status. Multivariate Cox proportional hazards models were employed to investigate the association between BDP and the risk of miscarriage. BDP was practiced for 6% of the total time at risk of miscarriage. The miscarriage rate was higher when mothers exclusively breast-fed during pregnancy (35%) than when they practiced either complementary BDP (i.e., the child also consumed other food) or did not breast-feed (14% and 15%, respectively). After adjustment for maternal and pregnancy characteristics, the risk of miscarriage was greater when mothers exclusively breast-fed than when mothers did not breast-feed (hazard ratio, 3.9), but no increased risk was found with complementary BDP. The miscarriage risk during exclusive BDP was similar to that for women who conceived when they were 40 or older (3.2). Exclusive BDP is associated with an elevated risk of miscarriage, but it remains unclear whether and how the practice is associated with health outcomes for the mother and breast-fed child. Research is needed to further explore these outcomes to inform recommendations regarding BDP.


Frontal hypermetabolism and thalamic hypometabolism in a patient with abnormal orienting and retrosplenial amnesia.
A patient with verbal amnesia and a propensity to direct his attention to the right following a retrosplenial area lesion was studied with positron emission tomography using [F-18] fluorodeoxyglucose. These studies showed that the left thalamus was hypometabolic, and the anterior 2/3 of the left hemisphere was hypermetabolic when compared with the right. There were no significant differences seen in the medial temporal lobes. Based on this study, it is posited that interruption of hippocampal input into the anterior thalamus was responsible for the amnesia, and the left frontal hyperactivity was associated with the propensity to attend contralaterally.


[Giardiasis].
Giardia Lamblia is considered as the most important cause of parasitic diarrhoea in children and adults. The epidemiology of the infection is determined by environmental and regional factors. The sensitivity of man for this infection depends on factors related to man himself and his environment. Structural changes of the gut such as cellular infiltration and villous atrophy, and functional derangements like malabsorption can explain part of the symptoms. The application of different procedures for the parasitological diagnosis with a variable degree of sensitivity is the cause of difference in recorded prevalence data. This infectious disease can be treated with a number of drugs; single dose treatment is to be preferred especially in childhood. Results of treatment i.a. with a single dose ornidazole are reported.


RETRACTED: Redox regulation of the glutathione reductase/iso-glutaredoxin system in germinating pea seed exposed to cadmium.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The editors would like to confirm the retraction of this paper at the request of the co-authors who had no prior knowledge on the actions of the lead author. This article contains data that was duplicated in: Smiri M, Chaoui A, Rouhier N, Gelhaye E, Jacquot JP, El Ferjani E. Cadmium Affects the Glutathione/Glutaredoxin System in Germinating Pea Seeds. Biol. Trace Elem. Res., 142 (2010) 93-105, doi:10.1007/s12011-010-8749-3; Smiri M, Chaoui A, Rouhier N, Gelhaye E, Jacquot JP, El Ferjani E. Effect of cadmium on resumption of respiration in cotyledons of germinating pea seeds. Ecotox. Environ. Safe., 73 (2010) 1246-1254, doi:10.1016/j.ecoenv.2010.05.015; Smiri M, Chaoui A, Rouhier N, Gelhaye E, Jacquot JP, El Ferjani E. NAD pattern and NADH oxidase activity in pea (Pisum sativum L.) under cadmium toxicity. Physiol. Mol. Biol. Plants, 16 (2010) 305-315, doi:10.1007/s12298-010-0033-7; Smiri M, Chaoui A, Rouhier N, Gelhaye E, Jacquot JP, El Ferjani E. Oxidative damage and redox change in pea seeds treated with cadmium. C. R. Biol., 333 (2010) 801-807, doi:10.1016/j.crvi.2010.09.002; Smiri M, Chaoui A, Rouhier N, Kamel C, Gelhaye E, Jacquot JP, El Ferjani E. Cadmium induced mitochondrial redox changes in germinating pea seed. BioMetals, 23 (2010) 973-984, doi:10.1007/s10534-010-9344-y. The co-authors apologize for this unfortunate incident.


Effect of high level section of the spinal cord on the cyclic AMP system in rat liver.
The effect of high level section of the spinal cord upon the hepatic cyclic AMP system was investigated in the rat. We report that transection of the spinal cord dramatically decreases the basal level of cyclic AMP from 0.88 nmol/g liver to 0.36 nmol/g at 1 h and to 0.20 nmol/g at 4 h. This was not due to increased activity of cyclic AMP phosphodiesterase or to decreased activity of basal adenylate cyclase. The sensitivity of adenylate cyclase to its usual effectors in vitro was not impaired. It is proposed that the lowering of liver cyclic AMP below its basal level after high level section of the spinal cord is due to decreased levels of hepatic catecholamines and/or plasma glucagon.


Investigating the reproducibility of maximal oxygen uptake responses to high-intensity interval training.
To test the hypothesis that observed maximal oxygen uptake (VO2max) and time to fatigue (TTF) responses to two identical periods of standardized high-intensity interval training are reproducible. Fourteen recreationally active and healthy young males completed two identical four-week periods of high-intensity interval training (4×4-min intervals at 90-95% maximum heart rate [HRmax] separated by 3-min periods of active recovery at 70-75% HRmax). Training periods were separated by a three-month washout period. VO2max and TTF were assessed via incremental tests with supramaximal verification before and after each training period. Pearson correlation coefficients (r), intraclass correlation coefficients (ICC), and within-subjects coefficients of variation (CV) were used to assess reproducibility of observed VO2max and TTF responses. VO2max and TTF values before the second training period were not significantly higher than baseline values and there were no significant (p>0.05) interaction effects (period 1: VO2max: +4.04±2.29mL/kg/min, TTF: +70.75±35.87s; period 2: VO2max: +2.83±2.74mL/kg/min, TTF: +83.46±34.55s). We found very weak-to-moderate correlations and poor reproducibility for observed VO2max (mL/kg/min: r=0.40, ICC=0.369, CV=74.4) and TTF (r=0.11. ICC=0.048, CV=45.6) responses to training periods 1 and 2. Our ANOVA results confirmed that the three-month washout period returned VO2max and TTF levels to baseline and prevented carryover effects. Contrary to our hypothesis, our results suggest that individual observed VO2max and TTF responses to identical training stimuli are not reproducible.


A practical thrice weekly ertapenem in hemodialysis patients.
Change of ertapenem dosage from 500 mg daily to thrice weekly after each hemodialysis session can maintain the plasma concentration above 2 mg/L, and be practical in hemodialysis patients.


Gas-phase and aqueous-surface reaction mechanism of Criegee radicals with serine and nucleation of products: A theoretical study.
Criegee intermediates (CIs) are short-lived carbonyl oxides, which can affect the budget of OH radicals, ozone, ammonia, organic/inorganic acids in the troposphere. This study investigated the reaction of CIs with serine (Ser) in the gas phase by using density functional theory (DFT) calculations and at the gas-liquid interface by using Born-Oppenheimer molecular dynamics (BOMD). The results reveal that the reactivity of the three functional groups of Ser can be ordered as follows: COOH > NH2 > OH. Water-mediated reactions of CIs with NH2 and OH groups of Ser on the droplet follow the proton exchange mechanism. The products, sulfuric acids, ammonia, and water molecules form stable clusters within 20 ns. This study shows that hydroperoxide products can contribute to new particle formation (NPF). The result deepens the understanding of the reaction of CIs with multifunctional pollutants and atmospheric behavior of CIs in polluted areas.


Valorization of the pelagic Sargassum horneri for co-production of erythritol and alginate oligosaccharides.
Pelagic Sargassum is invasive macroalgae with huge biomass. To produce bulk chemicals with profit from the biomass, innovative strategies need to be developed. In this study, maximum saccharification yield of Sargassum horneri biomass was obtained with the combined use of 3% alginate lyase and 3% cellulase, releasing 20.83 g/L glucose and 1.73 g/L mannitol at a 1:6 feed ratio. Subsequently, the crude S. horneri hydrolysate (pH 3.0) was proved most suitable for erythritol production of Yarrowia lipolytica strain. After 60 h fermentation in a 10-L fermenter, the erythritol concentration reached 18.42 g/L with a yield of 0.82 g/g; while the concentration of alginate oligosaccharides (AOS) was 37.56 g/L. Finally, AOS with a purity of 93.4% were obtained by ethanol precipitation, and erythritol was harvested via crystallization. This proposed strategy demonstrates the feasibility of transforming invasive Sargassum into two high-value chemicals for the first time.


Oscillating light engine realized by photothermal solvent evaporation.
Continuous mechanical work output can be generated by using combustion engines and electric motors, as well as actuators, through on/off control via external stimuli. Solar energy has been used to generate electricity and heat in human daily life; however, the direct conversion of solar energy to continuous mechanical work has not been realized. In this work, a solar engine is developed using an oscillating actuator, which is realized through an alternating volume decrease of each side of a polypropylene/carbon black polymer film induced by photothermal-derived solvent evaporation. The anisotropic solvent evaporation and fast gradient diffusion in the polymer film sustains oscillating bending actuation under the illumination of divergent light. This light-driven oscillator shows excellent oscillation performance, excellent loading capability, and high energy conversion efficiency, and it can never stop with solvent supply. The oscillator can cyclically lift up a load and output work, exhibiting a maximum specific work of 30.9 × 10-5 J g-1 and a maximum specific power of 15.4 × 10-5 W g-1 under infrared light. This work can inspire the development of autonomous devices and provide a design strategy for solar engines.


Determination of zearalenone in traditional Chinese medicinal plants and related products by HPLC-FLD.
A HPLC-FLD method has been developed and validated for zearalenone (ZON) in 107 widely consumed Chinese medicinal herbs and related products collected from different regions of China. Samples were extracted with methanol/water (80 : 20, v/v), and the extracts were cleaned-up through immunoaffinity columns (IAC). ZON was quantified by HPLC with fluorescence detection. Recoveries from three different medicinal herbs spiked with ZON at levels ranging from 30 to 600 µg kg(-1) were from 80.8 to 98.3%. The limit of detection was 9.5 µg kg(-1), based on a signal-to-noise ratio of 3 : 1. Naturally occurring ZON was only found in coix seed medicinal herb (all nine samples), with levels ranging from 18.7 to 211.4 µg kg(-1). Positive results were confirmed by UV spectrum and LC-ESI-MS/MS. This is the first report of ZON contamination of a Chinese medicinal herb.


Copper toxicosis and tolerance in the rat. III. Intracellular localization of copper in the liver and kidney.
Male rats fed a 3 g/kg copper diet were killed sequentially up to 14 weeks. Copper in liver and kidney cortex was identified histochemically and assayed in homogenates and gradient fractions following analytical subcellular fractionation on reorientating sucrose density gradients. Copper accumulated fastest in the liver postnuclear (PNS) supernatant fraction which became saturated at 2 weeks; there was a distinct localization of copper in hepatic lysosomes which displayed progressively enhanced fragility. Rapid accumulation of copper then occurred in liver and kidney nuclear (N) fractions, peak copper concentrations coinciding with hepatic and renal tubular necrosis. Copper accumulated slowly up to 4 weeks and was maintained to 14 weeks in the cytosol of the proximal renal tubules from which it appeared to be excreted. Subsequently liver copper declined in both liver fractions and kidney (N) fractions; hepatic lysosomes regained stability, regeneration of liver and kidney occurred, and the rats were tolerant to continued copper administration. These findings do not support a primary role for copper-loaded lysosomes in the genesis of cell injury, but suggest that nuclear saturation may be the destabilizing event. Recovery is associated with changes in the subcellular distribution of copper within liver and kidney and renal excretion of excess.


Fluorescence probes used for detection of reactive oxygen species.
Endogenously produced pro-oxidant reactive species are essential to life, being involved in several biological functions. However, when overproduced (e.g. due to exogenous stimulation), or when the levels of antioxidants become severely depleted, these reactive species become highly harmful, causing oxidative stress through the oxidation of biomolecules, leading to cellular damage that may become irreversible and cause cell death. The scientific research in the field of reactive oxygen species (ROS) associated biological functions and/or deleterious effects is continuously requiring new sensitive and specific tools in order to enable a deeper insight on its action mechanisms. However, reactive species present some characteristics that make them difficult to detect, namely their very short lifetime and the variety of antioxidants existing in vivo, capable of capturing these reactive species. It is, therefore, essential to develop methodologies capable of overcoming this type of obstacles. Fluorescent probes are excellent sensors of ROS due to their high sensitivity, simplicity in data collection, and high spatial resolution in microscopic imaging techniques. Hence, the main goal of the present paper is to review the fluorescence methodologies that have been used for detecting ROS in biological and non-biological media.


The complex interplay between semantics and grammar in impression formation.
We sought to bridge findings showing that (a) describing a person's behavior with the perfective verb aspect (did), compared to the imperfective aspect (was doing), increases processing of semantic knowledge unrelated to the target's action such as stereotypes and (b) an increased recognition of stereotypical thoughts often promotes a judgment correction for the stereotypes. We hypothesized an interplay between grammar (verb conjugation) and semantic information (gender) in impression-formation. Participants read a resume, attributed to a male or female, for a traditionally masculine job. When the resume was written in the imperfective, people rated a male (vs. female) more positively. When the resume was in the perfective, this pattern reversed. Only these latter effects of gender were influenced by cognitive load. Further, people more quickly indicated the applicant's gender in the perfective condition, suggesting an enhanced focus on gender during processing.


The laparoscopic management of post-transplant lymphocele. A critical review.
The managements of lymphocele in patients following kidney (KT) and pancreas (KPT) transplantation is evolving. Open surgery has been the traditional treatment, but some authors have advocated laparoscopic drainage in selected patients. We retrospectively reviewed our results in lymphocele treatment since developing a laparoscopic program at our institution. Between May 1994 and June 1995, 186 KTs and 48 KPTs were performed, and 1,354 patients are currently being followed. Eight patients developed symptomatic lymphoceles an average of 26 months (range 4-59) following 6 KTs and 2 KPTs. All patients diagnosed were successfully drained laparoscopically, with no conversions to open surgery. Laparoscopic ultrasound was used to help with localization of the fluid collection. Operative time averaged 59 min, median hospital stay was 1 day (range 1-4), and there were no perioperative complications. Follow-up imaging was obtained on six patients, 3-16 months following their procedures, and no recurrences were noted. A review of the literature demonstrates a 5.3% rate of major complications and a 7% incidence of lymphocele recurrence. Intraoperative laparoscopic ultrasound can help to localize fluid collections and prevent organ injuries. Laparoscopic drainage of lymphocele following transplantation results in minimal disability and an acceptable complication rate, although it is higher than with open drainage. Therefore, laparoscopic drainage should be considered as primary treatment for all patients with symptomatic post-transplant lymphocele.


In situ orderly self-assembly strategy affording NIR-II-J-aggregates for in vivo imaging and surgical navigation.
J-aggregation, an effective strategy to extend wavelength, has been considered as a promising method for constructing NIR-II fluorophores. However, due to weak intermolecular interactions, conventional J-aggregates are easily decomposed into monomers in the biological environment. Although adding external carriers could help conventional J-aggregates stabilize, such methods still suffer from high-concentration dependence and are unsuitable for activatable probes design. Besides, these carriers-assisted nanoparticles are risky of disassembly in lipophilic environment. Herein, by fusing the precipitated dye (HPQ) which has orderly self-assembly structure, onto simple hemi-cyanine conjugated system, we construct a series of activatable, high-stability NIR-II-J-aggregates which overcome conventional J-aggregates carrier's dependence and could in situ self-assembly in vivo. Further, we employ the NIR-II-J-aggregates probe HPQ-Zzh-B to achieve the long-term in situ imaging of tumor and precise tumor resection by NIR-II imaging navigation for reducing lung metastasis. We believe this strategy will advance the development of controllable NIR-II-J-aggregates and precise bioimaging in vivo.


Microscopic characterization of particle size and shape: an inexpensive and versatile method.
A variety of methods exists for measuring individual particle dimensions as a means of characterizing particle size, size distribution, and shape. The equipment described in this report belongs to the class of semiautomatic non-TV-interfaced analyzers. Unlike many existing image analysis systems, three-dimensional form measurements and texture data for the calculation of particle size and shape parameters can be determined easily and directly from each particle profile using this system. Essentially all data are collected directly from the particle and recorded by the computer with no intermediate steps. Much of the system consists of general-purpose and relatively inexpensive, commercially available hardware and software. Using this method, particle size, size distribution, and qualitative or quantitative shape information can easily and rapidly be obtained simultaneously. Particle length and width characterization, for example, can take less than 15 min. The equipment is versatile and flexible in measurements and calculations. The size and shape parameters to be measured are determined by the researcher and not the instrument. The ease with which this information can be obtained from small samples early in the development process makes it a valuable tool for the formulator.


Tactical Combat Casualty Care: Beginnings.
Tactical Combat Casualty Care (TCCC) is a set of evidence-based, best-practice prehospital trauma care guidelines customized for use on the battlefield. The origins of TCCC were nontraditional. The TCCC program began as a Naval Special Warfare biomedical research effort launched after the realization that extremity hemorrhage, a leading cause of preventable death on the battlefield, was not being treated with a readily available and highly effective intervention: the tourniquet. This insight prompted a systematic reevaluation of all aspects of battlefield trauma care that was conducted from 1993 to 1996 as a joint effort by special operations medical personnel and the Uniformed Services University of the Health Sciences. The product of that 3-year research project was TCCC, the first-ever set of battlefield trauma care guidelines designed to combine good medicine with good small-unit tactics.


Low incidence of IL6ST (gp130) mutations in exon 6 in lung cancer of a Chinese cohort.
Lung cancer is an inflammation-associated epithelial carcinoma. A highly active interleukin 6 (IL-6)/glycoprotein 130 (gp130)/signal transducer and activator of transcription 3 (STAT3) pathway has been identified in a subset of primary lung cancer and closely correlated with tumor progression and poor prognosis. In a previous study, the frequent occurrence of somatic gain-of-function mutations was observed in the gp130-encoding IL6ST gene in exon 6 in 60% of inflammatory hepatocellular adenomas. Prompted by this finding, we assessed 110 Chinese lung carcinomas using PCR and direct DNA sequencing but found no somatic mutation of IL6ST in exon 6. However, one new potential germline missense mutation c.599C>G was identified in one adenocarcinoma that harbors wild-type epidermal growth factor receptor and KRAS. Protein modeling analysis showed that this mutation might not affect the gp130 protein conformation. Moreover, activated STAT3 was observed in most of the lung tumor tissues at a higher level than that in matched normal lung tissues. In conclusion, the c.599C>G mutation may be a new single nucleotide polymorphism of IL6ST, but mutations in exon 6 of this gene are not apparently common genetic variations occurring and leading to constitutive activation of STAT3 in lung cancer.