The search for a culture system for papillomavirus.
Papillomaviruses induce tumors of keratinocytes. Vegetative viral DNA replication and virion assembly are seen in those cells which are in the process of keratinizing or are keratinized. To date, no cell culture system has been developed that permits expression of the complete viral life cycle. Keratinocytes infected in culture may harbor the virus as a stable, replicating episome, but they do not support vegetative viral growth, nor do they become immortalized or transformed. The major obstacle in using keratinocyte cultures may be related to a dual need for transformation and full differentiation. Some animal papillomaviruses have been shown to be capable of transforming cultured murine fibroblasts. The fibroblast model is useful for identifying the viral-transforming gene(s) and their products.


PrEP use and unmet PrEP-need among men who have sex with men in London prior to the implementation of a national PrEP programme, a cross-sectional study from June to August 2019.
Access to prevention options, including HIV pre-exposure prophylaxis (PrEP), remains a public health priority for gay, bisexual, and other men who have sex with men (MSM), especially in London. We describe PrEP use in a London community sample of MSM before the introduction of a national PrEP programme in October 2020. From June-August 2019, MSM aged ≥ 18 recruited from London commercial venues were asked to self-complete a sexual health questionnaire and provide an oral fluid sample for anonymous HIV antibody testing. Descriptive analyses of demographic characteristics, service engagement and outcomes, as well as sexual risk and prevention behaviours were examined in the survey population and in those reporting current PrEP use. We performed sequential, multivariate analyses examining current PrEP use in MSM of self-perceived HIV-negative/unknown status with identified PrEP-need defined as the report of condomless anal sex (CAS) in the last three months, or the report of CAS (in the last year) with an HIV-positive/unknown status partner not known to be on HIV treatment, in reflection of UK PrEP guidelines. One thousand five hundred and thirty-fifth questionnaires were completed across 34 venues, where 1408 were analysed. One in five MSM of self-perceived HIV-negative/unknown status reported current PrEP use (19.7%, 242/1230). In men with PrEP-need, 68.2% (431/632) did not report current use. Current PrEP use was associated with age (aOR: 3.52, 95% CI: 1.76-7.02 in men aged 40-44 vs men aged 18-25) and education (aOR: 1.72, 95% CI: 1.01-2.92 in men with ≥ 2 years/still full-time vs no/ < 2 years of education since age 16). Among MSM in London, PrEP use is high but there is indication of unmet PrEP-need in men of younger age and lower levels of post-16 education. National programme monitoring and evaluation will require continued community monitoring to guide interventions ensuring equitable PrEP access and uptake in those who could most benefit from PrEP.


Blood exchanged in ritual ceremonies as a possible route for infection with hepatitis C virus.
Of 52 blood donors (25 men and 27 women) counselled because their donation tested positive for hepatitis C virus antibody, seven (13.5%) gave a history of practising the ritual of blood exchange in their childhood or early adult life. This practice can cause transmission of blood borne infections or alloimmunisation, or both.


Profound reduction in brain embolization using an endoaortic baffle during bypass in swine.
Cerebral embolization during cardiopulmonary bypass is an important cause of neurologic injury. This study determined whether an endoaortic baffle catheter (Cardeon Cobra Catheter; Cardeon Corporation, Cupertino, CA) could substantially reduce cerebral embolization in a swine cardiopulmonary bypass model. Sixteen 60 kg pigs underwent cardiopulmonary bypass; 8 animals with the Cobra baffle (Cardeon Corporation, Cupertino, CA) deployed, and 8 with the same cannula without baffle deployment. The animals were embolized with 72,000 fluorescent microspheres (97 to 100 microm) at normothermia. At the end of the experiment, the brains were removed and microspheres were isolated from eight regions. During embolization, the two groups were equivalent with regard to pump flow, mean arterial pressure, temperature, Hgb and PaCO2. Deployment of the Cobra baffle reduced embolization to every brain region. Deployment of the baffle reduced total brain embolization by 89%. There was a mean of 61+/-60 emboli per gram in the control animals and 7+/-24 emboli per gram in those animals in which the baffle was deployed. Cerebral embolization is profoundly reduced by use of the Cobra baffle aortic cannula. The application of this device may reduce postcardiac surgical neurologic injury.


Development of competency based standards An application of the Delphi research technique.
This paper, by Ann Bonner and Glenn Stewart, describes the benefits and limitations of using the Delphi technique research method. The technique was applied to a study in Australia that sought to identify advanced practice competency standards within a nursing speciality.


Carbohydrate Ingestion during Prolonged Cycling Improves Next-Day Time Trial Performance and Alters Amino Acid Concentrations.
Exercise with low carbohydrate availability increases protein degradation, which may reduce subsequent performance considerably. The present study aimed to investigate the effect of carbohydrate ingestion during standardized exercise with and without exhaustion on protein degradation and next-day performance. Seven trained male cyclists (V̇O 2max 66.8 ± 1.9 mL·kg -1 ·min -1 ; mean ± SEM) cycled to exhaustion (~2.5 h) at a power output eliciting 68% of V̇O 2max (W 68% ). This was followed by repeating 1-min work/1-min recovery intervals at 90% of V̇O 2max (W 90% ) until exhaustion. During W 68% , cyclists consumed a placebo water drink (PLA) the first time and a carbohydrate drink (CHO), 1 g carbohydrate·kg -1 ·h -1 , the second time. The participants performed the same amount of work under the two conditions, separated by at least 1 wk. A standardized diet was provided to the participants so that the two conditions were isoenergetic. To test the impact of carbohydrates on recovery, participants completed a time trial (TT) the next day. Carbohydrate ingestion maintained carbohydrate availability during W 68% and W 90% : total carbohydrate oxidation was significantly higher in CHO ( P = 0.022), and plasma glucose concentration was maintained compared with PLA ( P = 0.025). Next-day performance during TT was better after CHO ingestion (CHO, 41:49 ± 1:38 min; PLA, 42:50 ± 1:46 min; P = 0.020; effect size d = 0.23, small), as was gross efficiency (CHO, 18.6% ± 0.3%; PLA, 17.9% ± 0.3%; P = 0.019). Urinary nitrogen excretion ( P = 0.897) and urinary 3-methylhistidine excretion ( P = 0.673) did not significantly differ during the study period. Finally, tyrosine and phenylalanine plasma concentrations increased in PLA but not in CHO ( P = 0.018). Carbohydrate ingestion during exhaustive exercise reduced deterioration in next-day performance through reduced metabolic stress and development of fatigue. In addition, some parameters point toward less protein degradation, which would preserve muscle function.


[Experimental Mycoplasma infection of the urogenital tract in monkeys].
The possibility of the experimental reproduction of infectious urethritis in monkeys by infecting them with mycoplasma and ureaplasma cultures, newly isolated from human patients, has been shown. In monkeys inoculated with the mixture of mycoplasmas and ureaplasmas, more pronounced infectious urethritis with the symptoms of ascending infection develops. The animals who have had the disease do not develop resistance to repeated infection.


Reanalysis of stone manipulation prior to extracorporeal shock wave lithotripsy for management of upper ureteral calculi.
In situ extracorporeal shock wave lithotripsy (ESWL) for upper ureteral stones is controversial, in contrast to ESWL treatment of the majority of other renal calculi. Some urologists recommend retrograde mobilization of the calculi into the renal pelvis prior to ESWL as a routine procedure, while others report little advantage in manipulating a ureteral stone into the kidney before treatment by ESWL. To better understand this controversial issue, we reanalyzed clinical studies and the mechanism of stone disintegration in ESWL. We performed a computerized MEDLINE search and manual bibliographic review of relevant peer reviewed reports from 1980 to 1998. Ten reports were analyzed with respect to stone-free rate and the important findings are summarized. Two of 10 data sets are statistically significant (p < 0.05) to verify a higher stone-free rate and another five reports also revealed that higher stone-free rates could be expected with retrograde stone manipulation into the renal collecting system before treatment by ESWL. Higher stone-free rates with retrograde stone manipulation into the renal collecting system before treatment by ESWL is statistically significant and theoretically supported by the mechanism of stone disintegration.


Inorganic-organic hybrid compounds based on novel lanthanide-antimony oxohalide nanoclusters.
Presented here is the assembly of two inorganic-organic hybrid compounds by the combination of novel praseodymium-antimony oxochloride clusters and dicarboxylic ligands co-directed by 2-MepyH and Fe(1,10-phen)(3) (or Fe(2,2'-bpy)(3)), which feature a two-fold interpenetrating three-dimensionally anionic network and a one-dimensionally helical anionic chain, respectively.


[Femoroacetabular impingement: association between the over-coverage and acetabular cartilage delamination areas].
Femoroacetabular impingement (FAI), it is a clinical syndrome relatively recently recognized as source of hip mechanic pain and early osteoarthritis. Two types of FAI have been described, based on the bone morphology and pattern of chondral and labral damage; the cam type is frequently associated with chondral delamination; and the pincer type is associated with a contre-coup injury of the posteroinferior acetabulum. A close relationship between the zone of acetabular overcoverage or retroversion and the area of acetabular chondral delamination has been observed. To evaluate the relationship between the acetabular overcoverage or retroversion zone, and the cartilage delamination area; and if by treating the overcoverage zone, the cartilage delamination area itself is also treated. A prospective evaluation was conducted on 16 patients (17 hips) with FAI and chondral delamination treated with acetabular trimming and labral reinsertion, and femoral bump resection. All cases had chondral delamination in the anterosuperior acetabular area, corresponding to the overcoverage or retroversion zone. In the 16 patients (94% of the hips) after the acetabular overcoverage bone resection, the remaining cartilage was stable and without delamination. Only one case (6%) required microfractures to treat the exposed subchondral bone after delaminated cartilage debridement. The acetabular chondral delamination area has a very close relationship with the acetabular overcoverage zone, meaning that the delamination area can be treated by trimming the overcoverage zone.


Involvement of Chk1-Cdc25A-cyclin A/CDK2 pathway in simvastatin induced S-phase cell cycle arrest and apoptosis in multiple myeloma cells.
Statins have been demonstrated to effectively inhibit proliferation and induce apoptosis in cancer cells by inhibition of geranylgeranylation, however its novel molecular mechanism remains to be determined. Recently simvastatin has been found to result in the synergistic induction of apoptosis with 7-hydroxystaurosporine (UCN-01) (a Chk1 inhibitor) in myeloma cells. Therefore we hypothesized that Chk1 plays a role in the anti-myeloma effect of simvastatin. Interestingly, we found that simvastatin caused a dose-dependent increase in S phase cell cycle and induced significant apoptosis. The results of western blot showed that simvastatin-induced S-phase cell cycle arrest was associated with activation of Chk1, downregulation of Cdc25A, cyclin A and CDK2 expression. Additionally, simvastatin-induced apoptosis was accompanied by diminished Bcl-2 protein expression, increased cytosolic cytochrome c level, and activation of caspase 9 and caspase 3. Further investigation revealed that silence of Chk1 expression by Chk1 specific siRNA inhibited simvastatin-induced activation of Chk1, downregulation of Cdc25A, cyclin A and CDK2 expression, and diminished S phase cell cycle arrest. Additionally, inhibition of Chk1 expression enhanced simvastatin-induced downregulation of Bcl-2, caspase 9 cleavage and subsequent apoptosis. These results suggested that the Chk1-Cdc25A-cyclin A/CDk2 pathway was involved in simvastatin-induced S-phase cell cycle arrest and apoptosis in multiple myeloma cell lines.


Modified Penicillin Molecule with Carbapenem-Like Stereochemistry Specifically Inhibits Class C β-Lactamases.
Bacterial β-lactamases readily inactivate most penicillins and cephalosporins by hydrolyzing and "opening" their signature β-lactam ring. In contrast, carbapenems resist hydrolysis by many serine-based class A, C, and D β-lactamases due to their unique stereochemical features. To improve the resistance profile of penicillins, we synthesized a modified penicillin molecule, MPC-1, by "grafting" carbapenem-like stereochemistry onto the penicillin core. Chemical modifications include the trans conformation of hydrogen atoms at C-5 and C-6 instead of cis, and a 6-α hydroxyethyl moiety to replace the original 6-β aminoacyl group. MPC-1 selectively inhibits class C β-lactamases, such as P99, by forming a nonhydrolyzable acyl adduct, and its inhibitory potency is ∼2 to 5 times higher than that for clinically used β-lactamase inhibitors clavulanate and sulbactam. The crystal structure of MPC-1 forming the acyl adduct with P99 reveals a novel binding mode for MPC-1 that resembles carbapenem bound in the active site of class A β-lactamases. Furthermore, in this novel binding mode, the carboxyl group of MPC-1 blocks the deacylation reaction by occluding the critical catalytic water molecule and renders the acyl adduct nonhydrolyzable. Our results suggest that by incorporating carbapenem-like stereochemistry, the current collection of over 100 penicillins and cephalosporins can be modified into candidate compounds for development of novel β-lactamase inhibitors.


Pyrocarbon interposition implant after lunate resection in Kienböck's disease: A case series.
In advanced stages of Kienböck's disease, the lunate is no longer conservable. One of the surgical options is to resect the lunate and replace it with a prosthesis. The procedure consisted in lunate resection and interposition of a free APSI® or Pi2® pyrocarbon implant through a dorsal approach. Follow-up was clinical and radiological on QuickDASH and PRWE scores. At a median follow-up of 3 years, 12 patients were reviewed, with a median age of 56 years. Flexion significantly decreased from 42° to 28° (p < 0.01). Extension and pronation-supination were conserved. Strength was 94% compared to the opposite side, with no significant difference from the preoperative measurement. Median QuickDASH and PRWE scores were 15.9 and 23.5 respectively and had significantly improved. One patient underwent scaphocapitate fusion because she was still in pain; the other patients were pain-free. No patients had to change jobs because of their wrist. Radiographically, there was no carpal collapse and carpal height was conserved. Radioscaphoid angle and ulnar translation were stable. There was 1 case of asymptomatic implant dislocation. Interposition of a pyrocarbon implant after lunate resection in advanced Kienböck's disease is a motion-conserving procedure that provides pain relief and functional recovery in the short and medium term. LEVEL OF EVIDENCE: IV.


Transparent multispectral photodetectors mimicking the human visual system.
Compact and lightweight photodetection elements play a critical role in the newly emerging augmented reality, wearable and sensing technologies. In these technologies, devices are preferred to be transparent to form an optical interface between a viewer and the outside world. For this reason, it is of great value to create detection platforms that are imperceptible to the human eye directly onto transparent substrates. Semiconductor nanowires (NWs) make ideal photodetectors as their optical resonances enable parsing of the multi-dimensional information carried by light. Unfortunately, these optical resonances also give rise to strong, undesired light scattering. In this work, we illustrate how a new optical resonance arising from the radiative coupling between arrayed silicon NWs can be harnessed to remove reflections from dielectric interfaces while affording spectro-polarimetric detection. The demonstrated transparent photodetector concept opens up promising platforms for transparent substrates as the base for opto-electronic devices and in situ optical measurement systems.


TIMELESS upregulates PD-L1 expression and exerts an immunosuppressive role in breast cancer.
Upregulation of the PD-L1 (CD274) immune checkpoint ligand on the tumor surface facilitates tumor immune escape and limits the application of immunotherapy in various cancers, including breast cancer. However, the mechanisms underlying high PD-L1 levels in cancers are still poorly understood. Bioinformatics analyses and in vivo and in vitro experiments were carried out to assess the association between CD8+ T lymphocytes and TIMELESS (TIM) expression, and to discover the mechanisms of TIM, the transcription factor c-Myc, and PD-L1 in breast cancer cell lines. The circadian gene TIM enhanced PD-L1 transcription and facilitated the aggressiveness and progression of breast cancer through the intrinsic and extrinsic roles of PD-L1 overexpression. Bioinformatic analyses of our RNA sequencing data in TIM-knockdown breast cancer cells and public transcriptomic datasets showed that TIM might play an immunosuppressive role in breast cancer. We found that TIM expression was inversely associated with CD8+ T lymphocyte infiltration in human breast cancer samples and subcutaneous tumor tissues. In vivo and in vitro experiments demonstrated that TIM knockdown increased CD8+ T lymphocyte antitumor activity. Furthermore, our results showed that TIM interacts with c-Myc to enhance the transcriptional capability of PD-L1 and facilitates the aggressiveness and progression of breast cancer through the intrinsic and extrinsic roles of PD-L1 overexpression. Moreover, public database analysis suggested that high TIM levels were positively related to PD-L1 inhibitor therapeutic response. Mechanistically, we first found that TIM could upregulate PD-L1 by interacting with c-Myc to enhance the transcriptional capability of c-Myc to PD-L1. Altogether, our findings not only provide a novel therapeutic strategy to treat breast cancer by targeting the oncogenic effect of TIM but also indicate that TIM is a promising biomarker for predicting the benefit of anti-PD-L1 immunotherapy.


Peroxyl radicals are essential reagents in the oxidation steps of the Maillard reaction leading to generation of advanced glycation end products.
Polyunsaturated fatty acids (PUFAs) are incorporated in all membranes of mammalian and plant cells and are extremely sensitive to oxygen. This property is used in nature to respond to any changes in cell membrane structure. In the first step of a response, lipid hydroperoxide molecules are generated. An increasing impact switches the enzymatic reaction to a nonenzymatic one by generation of lipid peroxyl radicals, which attack sugars by oxidation. In the course of these reactions, hydrogen peroxyl radicals are generated, resembling lipid peroxyl radicals in their reactivity. The reactions induced by these radicals are not under genetic control, they attack nearly all types of biological molecules (such as proteins, lipids, and sugars), and are responsible for the deleterious cell alterations in aging and age-related diseases (such as diabetes, Alzheimer's disease, or atherosclerosis) and probably also in autoimmune diseases, which involve sugars at the cell membranes. Lipid peroxidation processes are induced by heating fats, meat, and other nutritional products. The oxidation products generated by consumption of heated food cause damage of mammalian cells. The deleterious reactions can be partly reduced by consumption of plants and/or algae. These contain, among other well-known antioxidants, furan fatty acids, which are important scavengers of peroxyl radicals.


Electro-assisted methane oxidation to formic acid via in-situ cathodically generated H2O2 under ambient conditions.
Direct partial oxidation of methane to liquid oxygenates has been regarded as a potential route to valorize methane. However, CH4 activation usually requires a high temperature and pressure, which lowers the feasibility of the reaction. Here, we propose an electro-assisted approach for the partial oxidation of methane, using in-situ cathodically generated reactive oxygen species, at ambient temperature and pressure. Upon using acid-treated carbon as the electrocatalyst, the electro-assisted system enables the partial oxidation of methane in an acidic electrolyte to produce oxygenated liquid products. We also demonstrate a high production rate of oxygenates (18.9 μmol h-1) with selective HCOOH production. Mechanistic analysis reveals that reactive oxygen species such as ∙OH and ∙OOH radicals are produced and activate CH4 and CH3OH. In addition, unstable CH3OOH generated from methane partial oxidation can be additionally reduced to CH3OH on the cathode, and so-produced CH3OH is further oxidized to HCOOH, allowing selective methane partial oxidation.


Promoted aerobic denitrification through denitrifying fungal communities: Co-occurrence patterns and treatment of low C/N micro-polluted water.
Despite the growing interest in using mixed-culture aerobic denitrifying fungal flora (mixed-CADFF) for water remediation, there is limited research on their nitrogen removal performance in low C/N polluted water bodies. To address this knowledge gap, we isolated three mixed-CADFFs from overlying water in urban lakes to evaluate their removal performance. The total nitrogen (TN) removal efficiencies were 93.60 %, 94.64 %, and 95.18 %, while the dissolved organic carbon removal efficiencies were 96.64 %, 95.12 %, and 96.70 % for mixed-CADFF LN3, LN7, and LN15, respectively in the denitrification medium under aerobic conditions at 48 h cultivation. The three mixed-CADFFs could utilize diverse types of low molecular weight carbon sources to drive the aerobic denitrification processes efficiently. The optimal C/N ratio for the mixed-CADFFs were C/N = 10, and then C/N = 15, 7, 5, and 2. The high-throughput sequencing analysis of three mixed-CADFFs indicated that Eurotiomycetes, Cystobasidiomycetes, and Sordariomycetes were the dominant class in the communities at class level. The network analysis showed that the rare fungal species, such as Scedosporium dehoogii Saitozyma, and Candida intermedia presented positively co-occurred with the TN removal and organic matter reduction capacity. Immobilization mixed-CADFFs treatment raw water experiments indicated that three mixed-CADFFs could reduce nearly 62.73 % of TN in the low C/N micro-polluted raw water treatment. Moreover, the cell density and cell metabolism indexes were also increased during the raw water treatment. This study will provides new insight into resource utilization of the mixed-culture aerobic denitrifying fungal community in field of environment restoration.


Images in medicine: Diagnosis and pre-surgical triage of transanal rectal injury using multidetector CT with water-soluble contrast enema.
Transanal rectal injuries caused by foreign body insertion, sexual abuse, or iatrogenic procedures represent a very uncommon surgical emergency. Morbidity may be further increased by patient's embarrassment and delayed presentation. Since management decisions largely depend on anatomic and severity assessment, multidetector Computed tomography with rectally administered water-soluble iodinated contrast medium is highly valuable to accurately depict traumatic rectal injuries, and to distinguish between intraperitoneal vs extraperitoneal injuries that require different surgical approaches.


Mapping the time course of the positive classification advantage: an ERP study.
The aim of the present study was to investigate the time course of the positive advantage in the expression classification of faces by recording event-related potentials (ERPs). Although neutral faces were classified more quickly than either happy or sad faces, a significant positive classification advantage (PCA)-that is, faster classification for happy than for sad faces-was found. For ERP data, as compared with sad faces, happy faces elicited a smaller N170 and a larger posterior N2 component. The P3 was modulated by facial expressions with higher amplitudes and shorter latencies for both happy and neutral stimuli than for sad stimuli, and the reaction times were significantly correlated with the amplitude and latency of the P3. Overall, these data showed robust PCA in expression classification, starting when the stimulus has been recognized as a face revealed by the N170 component.


Online solid-phase extraction-inductively coupled plasma-quadrupole mass spectrometric quantification of 90Sr using 88Sr/86Sr isotope dilution method.
Due to the lack of a correlation with the natural Strontium (Sr) isotopes, it is difficult to apply the isotope dilution (ID) method to an artificial radioactive mononuclide Strontium-90 (90Sr), in inductively coupled plasma-quadrupole mass spectrometry (ICP-QMS). Meanwhile, online solid-phase extraction (SPE)-ICP-QMS (SPE-ICP-QMS) serves as an automatic sequential analytical technique for measuring the ultra-trace amounts of radionuclides; however, apparent assay values obtained using this method are often negatively affected by differences in the sample matrix composition between standard and actual samples. In this study, the pg L-1 level of 90Sr was successfully measured by combining online SPE-ICP-QMS and the ID method with 88Sr/86Sr ratios in one sample injection, without the radioactive standard. Although naturally occurring abundant isobaric 90Zr significantly influences 90Sr quantification during mass spectrometry, consecutive separations between automated SPE and dynamic reaction cell (DRC) oxidation enable 90Sr quantification, even in the presence of isobaric 90Zr (acceptable down to 5.7 × 10-9 of 90Sr/Zr in sample solution), using this method. Through this method, both radioactive 90Sr and naturally occurring Sr were simultaneously quantified using 88Sr-to-86Sr and 88Sr-to-90Sr ratios without radioactive 90Sr standard solutions. This simultaneous quantification of stable Sr and 90Sr was achieved within 15 min with good recovery rates. The limit of detection of 90Sr was 1.1 pg L-1 (equivalent to radioactivity 5.6 Bq L-1) for a 10 mL injection. Finally, water collected from an actual contaminated water storage tank at the Fukushima Daiichi Nuclear Power Plant (Fukushima, Japan) was analyzed using the proposed method, and the obtained results agreed well with those obtained using conventional analytical methods.


Multigenic regulation in the ethylene biosynthesis pathway during coffee flowering.
Ethylene regulates different aspects of the plant's life cycle, such as flowering, and acts as a defense signal in response to environmental stresses. Changes induced by water deficit (WD) in gene expression of the main enzymes involved in ethylene biosynthesis, 1-aminocyclopropane-1-carboxylic acid synthase (ACS) and oxidase (ACO), are frequently reported in plants. In this study, coffee (Coffea arabica) ACS and ACO family genes were characterized and their expression profiles were analyzed in leaves, roots, flower buds, and open flowers from plants under well-watered (WW) and water deficit (WD) conditions. Three new ACS genes were identified. Water deficit did not affect ACS expression in roots, however soil drying strongly downregulated ACO expression, indicating a transcriptional constraint in the biosynthesis pathway during the drought that can suppress ethylene production in roots. In floral buds, ACO expression is water-independent, suggesting a higher mechanism of control in reproductive organs during the final flowering stages. Leaves may be the main sites for ethylene precursor (1-aminocyclopropane-1-carboxylic acid, ACC) production in the shoot under well-watered conditions, contributing to an increase in the ethylene levels required for anthesis. Given these results, we suggest a possible regulatory mechanism for the ethylene biosynthesis pathway associated with coffee flowering with gene regulation in leaves being a key point in ethylene production and ACO genes play a major regulatory role in roots and the shoots. This mechanism may constitute a regulatory model for flowering in other woody species. The online version contains supplementary material available at 10.1007/s12298-022-01235-y.


Patient and parent perspectives on the utility of telemedicine for initial surgical gender care consultations: A cross-sectional survey.
The COVID-19 pandemic has expanded the use of telemedicine to patient populations that were previously constrained to in-person visits. Few studies have investigated the role that telemedicine plays in shaping the care of these patient populations. This project explores the impact of telemedicine for one such population: patients and parents of gender-diverse individuals seeking gender-affirming surgery. A 10-question survey using previously validated questions was completed by 34 patients and 9 parents of patients (aged 15-31) who received virtual care at the Center for Gender Surgery at Boston Children's Hospital between March 2020 and April 2021. The survey was divided into two parts. The first section collected demographic information. The second assessed participant perspectives on remote surgical gender care through a series of Likert-type and open-ended questions. A total of 100% of the respondents felt that their telemedicine visit was convenient; 60% (18) of the patients and 87% (7) of the parents stated that they look forward to future use of this modality. Free responses highlighted common perspectives on remote surgical gender care, including the increased accessibility of gender-affirming care through telehealth, the limitations of telehealth for addressing physical and relational aspects of gender care, patients' desire for autonomy and privacy during telehealth visits, and parents' desire to be involved throughout their children's gender journey. These results demonstrate the unique ability of telemedicine, if implemented thoughtfully, to enhance outcomes for patients seeking surgical gender affirmation.


The impact of anti-thymocyte globulin on the outcomes of Patients with AML with or without measurable residual disease at the time of allogeneic hematopoietic cell transplantation.
Measurable residual disease (MRD) status pre-allogeneic hematopoietic cell transplantation (allo-HCT) has been shown to predict transplant outcomes. We investigated the effect of Anti-Thymocyte Globulin (ATG) on acute myelogenous leukemia (AML) relapse by pretransplant MRD status. AML patients undergoing allo-HCT in first complete remission from either a matched sibling or unrelated donor during the 2006-2017 period were selected. Outcomes of 1509 patients (MRD+, n = 426) were studied. ATG was used in 561 (52%) and 239 (58%) patients within the MRD- and MRD+ cohorts, respectively. In MRD- patients, ATG did not affect relapse incidence (RI) (HR = 0.80, p = 0.17), but was associated with reduced incidence of grade II-IV acute GVHD, grade II-IV and chronic GVHD, reduced nonrelapse mortality (HR = 0.66, p = 0.05), improved leukemia-free survival (HR = 0.74, p = 0.02), overall survival (HR = 0.69, p = 0.01), and GVHD-relapse free survival (HR = 0.62, p < 0.01). In MRD+ patients, ATG was associated with a lower incidence of chronic GVHD (total, HR 0.56 p = 0.03; extensive, HR 0.40 P = 0.01), without an impact on other allo-HCT outcome parameters, including RI(HR = 1.02, p = 0.92). The use of ATG was associated with reduced risk for GVHD. ATG did not increase RI, even in high-risk AML patients who were MRD+ before allo-HCT.


CRISPR-Cas9-mediated therapeutic editing of Rpe65 ameliorates the disease phenotypes in a mouse model of Leber congenital amaurosis.
Leber congenital amaurosis (LCA), one of the leading causes of childhood-onset blindness, is caused by autosomal recessive mutations in several genes including RPE65. In this study, we performed CRISPR-Cas9-mediated therapeutic correction of a disease-associated nonsense mutation in Rpe65 in rd12 mice, a model of human LCA. Subretinal injection of adeno-associated virus carrying CRISPR-Cas9 and donor DNA resulted in >1% homology-directed repair and ~1.6% deletion of the pathogenic stop codon in Rpe65 in retinal pigment epithelial tissues of rd12 mice. The a- and b-waves of electroretinograms were recovered to levels up to 21.2 ± 4.1% and 39.8 ± 3.2% of their wild-type mice counterparts upon bright stimuli after dark adaptation 7 months after injection. There was no definite evidence of histologic perturbation or tumorigenesis during 7 months of observation. Collectively, we present the first therapeutic correction of an Rpe65 nonsense mutation using CRISPR-Cas9, providing new insight for developing therapeutics for LCA.


Isolation of new splice isoforms, characterization and expression analysis of the human septin SEPT8 (KIAA0202).
SEPT8 (KIAA0202) is a member of the highly conserved septin family. Septins are membrane-associated GTPases which are involved in cytokinesis and cellular morphogenesis. Using the yeast two-hybrid system and the glutathione-S-transferase pull-down assay we previously had identified the SEPT8 (KIAA0202) as interaction partner of the human septin SEPT5 (cell division cycle related-1, CDCrel-1). Since the complete cDNA sequence of the human septin SEPT8 (KIAA0202) was not known at that time, we isolated new 5' and 3' cDNA sequence of SEPT8 (KIAA0202) by screening three different cDNA libraries. In addition, we performed the characterization of SEPT8 (KIAA0202) and identified new splice variants of SEPT8 (KIAA0202). The expression pattern of SEPT8 (KIAA0202) and its interaction partner SEPT5 (CDCrel-1) is illustrated.


Quantification of specific bindings of biomolecules by magnetorelaxometry.
The binding reaction of the biomolecules streptavidin and anti-biotin antibody, both labelled by magnetic nanoparticles (MNP), to biotin coated on agarose beads, was quantified by magnetorelaxometry (MRX). Highly sensitive SQUID-based MRX revealed the immobilization of the MNP caused by the biotin-streptavidin coupling. We found that about 85% of streptavidin-functionalised MNP bound specifically to biotin-agarose beads. On the other hand only 20% of antibiotin-antibody functionalised MNP were specifically bound. Variation of the suspension medium revealed in comparison to phosphate buffer with 0.1% bovine serum albumin a slight change of the binding behaviour in human serum, probably due to the presence of functioning (non heated) serum proteins. Furthermore, in human serum an additional non-specific binding occurs, being independent from the serum protein functionality.The presented homogeneous bead based assay is applicable in simple, uncoated vials and it enables the assessment of the binding kinetics in a volume without liquid flow. The estimated association rate constant for the MNP-labelled streptavidin is by about two orders of magnitude smaller than the value reported for free streptavidin. This is probably due to the relatively large size of the magnetic markers which reduces the diffusion of streptavidin. Furthermore, long time non-exponential kinetics were observed and interpreted as agglutination of the agarose beads.


[Functional state of RBC and neutrophils in pneumoconiosis patients variable in tolerance to dust factor in after contact period].
The article covers basic mechanisms and major pathogenetic factors of pneumoconiosis formation and course in after contact period. The authors provide results of metabolic disorders analysis in the patients vairable in tolerance to industrial aerosol, to forecast pneumoconiosis course after discontinued contact with the hazard.


Influence of gonadal steroids on rat pituitary growth hormone secretion.
Growth hormone (GH) secretion increases at the time of puberty, and both androgens and estrogens increase the GH response to provocative agents. Little is known, however, with regard to the mechanism or site of action of gonadal steroid-stimulated GH secretion. Using monolayer primary cell culture and radioimmunoassay techniques, insulin-like growth factor I (IGF-I), purified and biosynthetic human GH, 17 beta-estradiol (E2), and testosterone (T) effects on GH release from rat anterior pituitary cells were investigated. Media content of rat GH was measured, both basally and after growth hormone releasing factor (GRF) stimulation. IGF-I at 50 nM concentration inhibited basal rGH release but not in GRF-stimulated cells. E2 (10 pM) stimulated basal secretion of rGH, although higher concentrations did not. High concentrations of T (100,000 pM) caused an increase in GRF-stimulated rGH secretion. Neither purified nor biosynthetic hGH pretreatment influenced subsequent rGH release. These results suggest that IGF-I inhibits and E2 (low dose) and T (high dose) augment rGH release in part at the level of the anterior pituitary.


Sympathetic ophthalmia: to the twenty-first century and beyond.
Sympathetic ophthalmia is a rare bilateral granulomatous inflammation that follows accidental or surgical insult to the uvea of one eye. Onset of sympathetic ophthalmia can be insidious or acute, with recurrent periods of exacerbation. Clinical presentation shows mutton-fat keratic precipitates, choroidal infiltrations, and Dalen-Fuchs nodules. Histopathology reveals diffuse or nodular granulomatous inflammation of the uvea. Prevention and treatment strategies for sympathetic ophthalmia are currently limited to two modalities, enucleation of the injured eye and immunosuppressive therapy, aimed at controlling inflammation. The etiology and pathophysiology of the disease is still unclear but is largely thought to be autoimmune in nature. Recent insight on the molecular pathology of the disease as well as developments in imaging technology have furthered both the understanding on the autoimmune process in sympathetic ophthalmia and the targeting of prevention and treatment strategies for the future.


Open conversion for laparoscopically difficult cholecystectomy is still a valid solution with unsolved aspects.
The difficult laparoscopic cholecystectomy remains a surgical challenge for surgeons who must decide between laparoscopic continuation and open conversion. The balance between the lack of open surgery training of young surgeons and the risk of maintaining the laparoscopic approach in difficult laparoscopic cholecystectomy is still an unresolved problem. Furthermore, the time that must be spent in an attempt to complete laparoscopic surgery before conversion is still controversial. The authors in this letter discuss about these and other questions that still require an answer.


On-line polymerase chain reaction (PCR) monitoring.
In this short note, we present the results of a case study for monitoring the whole polymerase chain reaction (PCR) process (all steps) with a glass fiber fluorometer that was described in a former publication. To utilize this fluorometer, which was originally constructed for a PCR machine with three thermostating devices, a new thermostating device has been developed: the glass fiber matrix is integrated into the thermostating device, while the PCR samples are heated and cooled. The device is able to monitor all samples throughout all stages of PCR with the help of an intercalating dye. This approach also permits one to choose arbitrarily different cooling and heating rates.


Surface pressure-dependent cross-modulation of sphingomyelinase and phospholipase A2 in monolayers.
We investigated the ways in which phospholipase A2 and sphingomyelinase are mutually modulated at lipid interfaces. The activity of one enzyme is affected by its own reaction products and by substrates and products of the other enzyme; all this depends differently on the lateral surface pressure. Ceramide inhibits both the sphingomyelinase activity rate and the extent of degradation, and decreases the lag time at all surface pressures. Dilauroyl- and dipalmitoylphosphatidylcholine, the substrates of phospholipase A2 (PLA2), do not affect sphingomyelinase activity. The products of PLA2, palmitic acid and lysopalmitoylphosphatidylcholine, strongly enhance and shift to high surface pressures the activity optimum and the cutoff point of sphingomyelinase. Palmitic acid also shifts to high surface pressures the cut-off point of PLA2 activity. Sphingomyelin strongly inhibits PLA2 at surface pressures above 5 mN/m, while ceramide shifts the cut-off point and the activity optimum to high surface pressures. The sphingolipids increase the lag time of PLA2 at low surface pressures. Both phosphohydrolytic pathways involve different levels of control on precatalytic steps and on the rate of activity that appear independent on specific alterations of molecular packing and surface potential. The mutual lipid-mediated interfacial modulation between both phosphohydrolytic pathways indicates that phospholipid degradation may be self-amplified or dampened depending on subtle changes of surface pressure and composition.


Hype or hope: Vagus nerve stimulation against acute myocardial ischemia-reperfusion injury.
Acute myocardial infarction (MI) is a major cause of death worldwide. Although timely and successful reperfusion could reduce myocardial ischemia injury, limit infarct size, and improve ventricular dysfunction and reduce acute mortality, restoring blood flow might also lead to unwanted myocardial ischemic-reperfusion (I/R) injury. Pre-clinical studies have demonstrated that multiple approaches are capable of attenuating the myocardial I/R injury. However, there is still no effective therapy for preventing myocardial I/R injury for the clinical setting. It is known that myocardial I/R injury could induce cardiac autonomic imbalance with over-activated sympathetic tone and reduced vagal activity, in turn, contributing to pathogenesis of myocardial I/R injury. Cumulative evidence shows that the enhancement of vagal activity, so called vagus nerve stimulation (VNS), is able to reduce injury and promote recovery of injured myocardium. Therefore, VNS might be a potentially novel strategy choice for preventing/attenuating myocardial I/R injury. In this review, we describe the protective role of VNS in myocardial I/R injury and related potential mechanisms. Then, we discuss the challenge and the opportunity of VNS in the treatment of acute myocardial I/R injury.


Role of the Yersinia YopJ protein in suppressing interleukin-8 secretion by human polymorphonuclear leukocytes.
Polymorphonuclear leukocytes, in addition to their direct bactericidal activities, produce cytokines involved in the activation and regulation of the innate and adaptive immune response to infection. In this study we evaluated the cytokine response of human PMNs following incubation with the pathogenic Yersinia species. Yersinia pestis strains with the pCD1 virulence plasmid, which encodes cytotoxic Yop proteins that are translocated into host cells, stimulated little or no cytokine production compared to pCD1-negative strains. In particular, PMNs incubated with pCD1-negative Y. pestis secreted 1000-fold higher levels of interleukin-8 (IL-8 or CXCL8), a proinflammatory chemokine important for PMN recruitment and activation. Deletion of yopE, -H, -T, -M or ypkA had no effect on pCD1-dependent inhibition, whereas deletion of yopJ resulted in significantly increased IL-8 production. Like Y. pestis, the enteropathogenic Yersinia species inhibited IL-8 secretion by PMNs, and strains lacking the virulence plasmid induced high levels of IL-8. Our results show that virulence plasmid-encoded effector Yops, particularly YopJ, prevent IL-8 secretion by human PMNs. Suppression of the chemotactic IL-8 response by Y. pestis may contribute to the delayed PMN recruitment to the infected lymph node that typifies bubonic plague.


Localization of the beta-like globin gene cluster and the genes for parathyroid hormone and c-Harvey-ras 1 to region q14----q21 of rabbit chromosome 1 by in situ hybridization.
The rabbit beta-like globin gene cluster (HBBC), comprised of epsilon-, gamma-, delta-, and beta-globin genes (HBE, HBG, HBD, and HBB, respectively), has been mapped to chromosome 1, region q14----q21, by in situ hybridization using probes for rabbit HBE and HBG. Probes for the human parathyroid hormone gene (PTH) and the Harvey-ras 1 protooncogene (HRAS1) also localize to this region by in situ hybridization. Thus, these genes are syntenic in lagomorphs as well as four other mammalian orders (primates, rodents, carnivores, and artiodactyls). The mapping data in rabbits provide further evidence that this synteny is strongly conserved in the evolution of mammalian chromosomes.


Effects of dietary fish oil on renal growth and function in uninephrectomized rats.
The basic mechanisms of renal growth remain poorly understood. The work hypertrophy theory holds that after an acute reduction in renal mass, the growth of the kidney occurs as a consequence of increased renal function. Pharmacological inhibition of renal prostaglandin synthesis impairs the acute adaptive increases in both renal function and mass following partial nephrectomy. The present study examines the effects of four weeks of dietary fish oil on renal growth, function and arachidonic acid metabolites in intact and uninephrectomized male Sprague-Dawley rats. Dietary fish oil interferes with dienoic prostaglandin and thromboxane production in favor of synthesis of trienoic analogues. Control animals were pair-fed an identical diet with the exception that the fat was replaced by beef tallow. Renal cortical concentrations of arachidonic acid metabolites were reduced in animals fed fish oil, and urinary excretion of prostaglandin E2 was impaired. Fish oil feeding resulted in increased kidney weight without concomitant increases in renal function in intact animals. Glomerular filtration rate and renal plasma flow were greater in uninephrectomized rats fed fish oil compared to uninephrectomized controls pair-fed beef tallow. Augmentation of the compensatory increases in renal function observed with fish oil feeding was not associated with any additional renal hypertrophy. These data indicate that dietary fish oil has a profound impact on renal growth and function, which may be the consequence of altered renal and/or extrarenal arachidonic acid metabolism. Furthermore, the direction of the alterations in renal mass oppose that of renal function, providing clear and unique evidence against the work hypertrophy theory of renal growth.


Migraine aura: new ideas about cause, classification, and clinical significance.
The migraine aura is a dramatic spontaneous change in brain activity resulting in a variety of transient neurological symptoms. The purpose of this review is to address recent advances in the understanding of aura and its role in migraine. The formal classification of migraine aura is becoming both broader and more detailed. Traditionally viewed as a primary event that triggers a migraine attack, studies regarding the timing of aura relative to other symptoms of migraine indicate that it may not in fact play a primary role in initiating an attack. Careful recording and analysis of visual aura symptoms provides new insight into the initiation and propagation of the underlying brain phenomenon, and the different regions of visual cortex that produce different visual perceptions. Migraine with aura may have different responses to acute and preventive therapies. There has been significant evolution of concepts regarding the causes of migraine aura, how it is best defined, and how it fits into the picture of the migraine disorder as a whole. Regardless of its exact role in the genesis of migraine, an increased understanding of aura has the potential to provide important new insight into not only migraine but also fundamental mechanisms of brain physiology.


44-kDal bone phosphoprotein (osteopontin) antigenicity at ectopic sites in newborn rats: kidney and nervous tissues.
Previous immunohistochemical data have shown that the 44-kDal bone phosphoprotein (44K BPP, also called sialoprotein I or oestopontin) recently isolated in our laboratory was synthesized by osteoblasts and osteocytes and was expressed early during differentiation of bone-forming cells. We report here the presence of 44K BPP antigenicity at certain ectopic sites, namely, the proximal-convoluted tubule of the kidney, neurons, sensory and secretory cells in the internal ear. To insure specificity and reproducibility, different immunohistochemical methods were used and affinity-purified antibodies against two separate preparations of pure 44K BPP were tested. In the cells of the proximal-convoluted tubule, 44K BPP immunoreactivity was observed within apical endocytotic vacuoles and within lysosomes. This staining thus correlates with the degradation of the 44K BPP epitope which we previously demonstrated to occur in serum. On the other hand, in the neurons of the acoustic ganglion and the sensory cells of the macula, 44K BPP immunoreactivity was associated with the Golgi apparatus indicating synthesis and secretion by these cells. The finding that the 44K BPP (or a structurally related molecule) is synthesized by neurons and neuroepithelial cells deserves further investigation with respect to a possible embryologic relationship between neuroectodermal cells and the precursors of some bone forming-cells of the skull.


Factors Associated with Suicidal Ideation and Suicide Attempt among School-Going Urban Adolescents in Peru.
The study examines the prevalence of suicidal ideation and suicide attempt, and associated factors among school-going urban adolescents in Peru. A cross-sectional survey was conducted in a sample of 916 secondary school adolescents in 2014. A structured questionnaire adapted from Global School-based Student Health Survey was used to obtain information. Data were analyzed using logistic regression models at 5% level of significance. Overall, 26.3% reported having suicidal ideation, and 17.5% reported having attempted suicide during the past 12 months. Multivariate logistic regression analysis showed that female sex, being in a fight, being insulted, being attacked, perceived unhappiness, smoking and sexual intercourse initiation were significantly associated with increased risk of suicidal ideation, while female sex, being in a fight, being insulted, being attacked, perceived unhappiness, alcohol and illicit drug use were related to suicide attempt. The prevalence of suicidal ideation and suicide attempts observed in the survey area is relatively high. Female adolescents are particularly vulnerable to report suicidal ideation and suicide attempt. Interventions that address the issue of violence against adolescents, fighting with peers, health risk behaviors particularly initiation of smoking, alcohol and illicit drug use and encourage supportive role of parents may reduce the risk of suicidal behaviors.


Complicated jejunal diverticulitis: A case report and review of literature.
Jejunal diverticulitis is an uncommon pathology wherein a delay in diagnosis can lead to significant morbidity and mortality. We report a case of such diverticula requiring operative management, after patient failed non-operative management, likely due to advanced jejunal inflammation from a delay in diagnosis and subsequent management.


Intracranial tuberculomas and the CAT scan.
Tuberculomas of the brain are rare in the United States. Although CAT (computerized axial tomography) scanning cannot distinguish these infections from other intracranial mass lesions, it provides a non-invasive technique with which to follow the course of presumptive lesions during medical therapy, and with which to search for clinically unsuspected infections. The necessity for and timing of surgery can be considered more easily with this technique. Two cases are presented with their CAT scans, including one example of the disappearance of a presumptive tuberculoma, during appropriate medical therapy.


Detailed Study of the Influence of InGaAs Matrix on the Strain Reduction in the InAs Dot-In-Well Structure.
InAs/InGaAs dot-in-well (DWELL) structures have been investigated with the systematically varied InGaAs thickness. Both the strained buffer layer (SBL) below the dot layer and the strain-reducing layer (SRL) above the dot layer were found to be responsible for the redshift in photoluminescence (PL) emission of the InAs/InGaAs DWELL structure. A linear followed by a saturation behavior of the emission redshift was observed as a function of the SBL and SRL thickness, respectively. The PL intensity is greatly enhanced by applying both of the SRL and SBL. Finite element analysis simulation and transmission electron microscopy (TEM) measurement were carried out to analyze the strain distribution in the InAs QD and the InGaAs SBL. The results clearly indicate the strain reduction in the QD induced by the SBL, which are likely the main cause for the emission redshift.


[Effect of Qishen Huoxue Granule in treating severe sepsis].
To study the anti-inflammatory effect and the therapeutic efficacy of Qishen Huoxue Granule (QHG) in treating severe sepsis. One hundred and sixty-seven patients with severe sepsis were enrolled and randomly assigned to two groups, the 85 patients in the control group treated with conventional Western medicine and the 82 in the QHG group treated with conventional Western medicine plus QHG. Changes of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10), procalcitonin (PCT), Marshall score, APACHE II score, ICU stay time and 28-day mortality were monitored and compared. Compared with the control group, IL-6 and TNF-alpha levels, the ICU stay time and 28-day mortality were significantly lower in the QHG group (all P < 0.05). During the QHG treatment, no severe adverse event was observed. The integrative treatment could reduce the blood levels of IL-6 and TNF-alpha, shorten the ICU stay time and decrease the 28-day mortality of patients with sepsis, showing a favor therapeutic prospect.


Prenatal diagnosis for detection of aneuploidy: the options.
The value of all noninvasive prenatal tests must be viewed with the perspective of the consequences of invasive testing. Regarding second trimester noninvasive testing, biochemical screening is more accurate in establishing risk than maternal age alone. One or more major ultrasound abnormalities, nuchal thickening, or a shortened humerus should raise concern for Down syndrome regardless of the patient's a priori risk based on age or biochemical markers. Isolated minor ultrasound markers should not be used in calculating risk in low-risk patients regarding Down syndrome unless the biochemical profile already places the patient at risk or in a borderline risk zone. If the ultrasound finding is hyperechoic bowel, problems other than aneuploidy may be the cause, including cystic fibrosis, infection, or hemorrhage, and these problems must be considered if hyperechoic bowel is an isolated finding. Improved risk adjustment seems to be applicable to a priori high-risk patients with completely normal sonograms. Genetic sonograms with specific risk adjustment schemata may be used to adjust a priori risk (either maternal age or biochemical screening results) at centers in which this has proven to be accurate, but whether this is statistically sound remains to be determined. The goal of second trimester ultrasound screening is to identify at-risk fetuses better and offer invasive testing to a more select group of patients. As the value of first trimester screening becomes more evident and practical, and if the risk of chorionic villus sampling becomes an acceptable norm, the patient population that reaches the second trimester of pregnancy will be select. Therefore, we can anticipate that second trimester screening and invasive testing may be needed only in a minority of cases, and the practice standards of prenatal testing and sonography (including minor ultrasound markers) will change entirely.


Fourier analysis of videokeratography data: Clinical usefulness in grade I and subclinical keratoconus.
To evaluate the contribution of Fourier analysis of videokeratographic data in the diagnosis of subclinical keratoconus and keratoconus. Eye Institute of Thrace, Democritus University, Alexandroupolis, Greece. Observational case series. The following Pentacam-derived parameters, resulting from Fourier decomposition of keratometric data, were evaluated for their diagnostic capacity using receiver operating curves: spherical component and eccentricity, maximum decentration, regular astigmatism in the center and in the periphery, mean astigmatism, irregularities, regular astigmatism in the center plus the irregularities, and total astigmatism. Logistic regression was performed to identify a combined diagnostic model. The study comprised 80 keratoconus eyes, 55 eyes diagnosed with subclinical keratoconus, and 50 normal eyes. Significant differences were detected in spherical eccentricity, maximum decentration, irregularities, regular astigmatism in the center and in the periphery, regular astigmatism in the center plus the irregularities, mean astigmatism, and total astigmatism parameters between the groups. Almost all parameters had high diagnostic ability in both study groups (area under the curve >90%). Among individual parameters, those with the highest predictive accuracy were the regular astigmatism in the center plus the irregularities (subclinical keratoconus 97.6%, keratoconus 98.8%) and the maximum decentration (subclinical keratoconus 91.4%, keratoconus 98.5%). Sufficient predictive accuracy (subclinical keratoconus 99.4, keratoconus 100%) was identified in a diagnostic model that combined the regular astigmatism in the center plus the irregularities and the maximum decentration. Fourier decomposition of keratometric data provided parameters with high accuracy in differentiating corneas with subclinical keratoconus from normal corneas and should be included to allow prompt diagnosis of keratoconus. None of the authors has a financial or proprietary interest in any material or method mentioned.


[Family's and/or relatives expectations concerning a patient emergently hospitalized into an intensive care unit after out-of-hospital medical care of by a samu team].
Emergency admission of a patient into an intensive care unit (ICU) is a source of stress for family and/or relatives. Expectations of family and/or relatives are important endpoints for the medical and paramedical team in charge of the patient, to better answer to their questions. The aim of this study was to determine family's and/or relatives expectations concerning a patient emergently hospitalized into an ICU after out-of-hospital medical care of by a samu team. We performed a survey using a questionnaire sent by email to 500 randomly chosen individuals from the French population. We received 220 responses (44 %). Family and/or relatives expectations are different about short, medium and long terms. Elements perceived as the most important in the short term are severity, diagnosis and prognosis, whereas in the medium and long terms they are hospital-stay and potential sequels. Medical language used is considered as too much complex for more than half of respondents. In case of foreseeable unfavourable outcome, 90 % of respondents would like to receive immediate information using a simple and brief language. At last, nearly two thirds of respondents had been really exposed to such a situation before, and assessed the quality of information received as moderate, with a score of 5/10. Information of families and/or relatives of a patient hospitalized in ICU is essential. Their expectations concern short, medium and long terms. At last, most of them prefers that information would be delivered by a physician, and using a simple and brief language.


Impact of growth conditions on the occurrence ofFusarium spp. and the mycotoxin content of wheat.
In 1997-99 the occurrence ofFusarium spp. on winter wheat and the contamination with mycotoxins was investigated at three locations in the Rhineland, Germany. All cultivation methods investigated had an effect on the level ofFusarium infection, however, rainfall during flowering was the most important factor. The choice of cultivar and soil cultivation proved to be the most promising tools to reduce head scab severity and mycotoxin contamination.


Emotional facial expressions evoke faster orienting responses, but weaker emotional responses at neural and behavioural levels compared to scenes: A simultaneous EEG and facial EMG study.
In the current study, electroencephalography (EEG) was recorded simultaneously with facial electromyography (fEMG) to determine whether emotional faces and emotional scenes are processed differently at the neural level. In addition, it was investigated whether these differences can be observed at the behavioural level via spontaneous facial muscle activity. Emotional content of the stimuli did not affect early P1 activity. Emotional faces elicited enhanced amplitudes of the face-sensitive N170 component, while its counterpart, the scene-related N100, was not sensitive to emotional content of scenes. At 220-280ms, the early posterior negativity (EPN) was enhanced only slightly for fearful as compared to neutral or happy faces. However, its amplitudes were significantly enhanced during processing of scenes with positive content, particularly over the right hemisphere. Scenes of positive content also elicited enhanced spontaneous zygomatic activity from 500-750ms onwards, while happy faces elicited no such changes. Contrastingly, both fearful faces and negative scenes elicited enhanced spontaneous corrugator activity at 500-750ms after stimulus onset. However, relative to baseline EMG changes occurred earlier for faces (250ms) than for scenes (500ms) whereas for scenes activity changes were more pronounced over the whole viewing period. Taking into account all effects, the data suggests that emotional facial expressions evoke faster attentional orienting, but weaker affective neural activity and emotional behavioural responses compared to emotional scenes.


Restoration of E2F expression rescues vascular endothelial cells from tumor necrosis factor-alpha-induced apoptosis.
Normally, quiescent endothelial cells (EC) line the inner surface of arteries and protect against thrombosis and neointimal growth. A variety of noxious stimuli, including balloon angioplasty, may compromise EC integrity, thereby initiating proliferation and triggering the local release of cytokines, including tumor necrosis factor-alpha (TNF-alpha). In vivo blockade of TNF-alpha using a soluble receptor molecule results in accelerated reendothelialization at sites of balloon angioplasty, suggesting an important physiological role of TNF-alpha in attenuating regrowth of endothelium after balloon angioplasty. Our studies reveal that TNF-alpha, an apoptosis-inducing cytokine, induces G1 cell-cycle arrest in proliferating EC. Quiescent EC are relatively immune to TNF-induced apoptosis versus proliferating EC, which display repression of the E2F transcription factor coincident with TNF-induced apoptosis and cell-cycle arrest. We also show that in this setting, E2F overexpression exerts a survival effect in proliferating EC and restores cell-cycle progression, in direct contrast to results of prior reports, which revealed that deregulated expression of E2F in normally cycling cells induces apoptosis. These data demonstrate that TNF-induced apoptosis is highly dependent on cell-cycle activity and that E2F can function as survival factor under certain conditions.


Magnetic resonance imaging of deep vein thrombi correlates with response to thrombolytic therapy.
Fibrinolytic therapy can result in rapid lysis of deep vein thrombi (DVT), but its use is limited by the failure of many patients to respond and by the increased risk of bleeding complications in comparison with anticoagulant therapy alone. Treatment could be improved by the ability to select patients most likely to respond. Since magnetic resonance (MR) imaging may be sensitive to thrombus age and structure, properties related to thrombolytic sensitivity, we have evaluated the ability of MR imaging to predict the response of DVT to thrombolytic therapy. Nine patients with venographically documented proximal DVT were treated with streptokinase, and MR imaging using a gradient recall echo sequence was performed before and after therapy. The proximal leg veins were divided into nine segments in each patient, and thrombus was present in 55 segments. The MR appearance of the thrombus in each segment was evaluated prior to therapy, and the amount of clot lysis was determined by comparing pre- and post-treatment MR images. MR imaging accurately identified thrombus in all cases in comparison with venography and also identified proximal extension into pelvic veins that was not identified venographically. Prior to treatment, the thrombus in eight of nine patients varied in appearance in different vein segments consistent with a course of progressive extension over time. Thrombi with low MR signal occurred more often in patients with symptoms of four days or less, and were also more common in partially occluded segments (10/12, 83%) than with total occlusion (7/43, 16%) (p < .001).(ABSTRACT TRUNCATED AT 250 WORDS)


Pulmonary crystal-storing histiocytosis: a case report and literature review.
Crystal-storing histiocytosis is a rare non-neoplastic histiocytic proliferation disorder which can occur in many anatomic sites. Fewer than 20 cases of pulmonary crystal-storing histiocytosis have been reported, most of which were associated with clonal lymphoproliferative disorder. Herein we report the first case of pulmonary crystal-storing histiocytosis with underlying Sjögren syndrome.


Prediction of lateral lymph node metastasis using OSNA method for mesorectal lymph nodes in low rectal cancer: A prospective study by the Kanagawa Yokohama Colorectal Cancer Study Group (KYCC1801).
Contrary to the Japanese guidelines recommendations regarding lateral lymph node dissection (LatLND) for rectal cancer, its omission is common in clinical practice without reliable omission criteria. Negative pathological mesorectal lymph node metastasis (MesLNM) is reportedly highly correlated with negative pathological lateral lymph node metastasis (p-LatLNM); however, this cannot be used as a criterion because pathological features are revealed postoperatively. Herein, we prospectively evaluated the negative predictive value (NPV) of MesLNM diagnosed via the one-step nucleic acid amplification (OSNA) method for p-LatLNM. This prospective study was conducted at a single academic study group in Japan. The key eligibility criterion was mid-to-low rectal cancer planned to be treated using mesorectal excision with LatLND. According to the study protocol, the OSNA method was considered useful if the point estimate of the NPV exceeded 95%. Preoperative case registration was conducted between 2018 and 2020; 34 patients were registered. Among these, 16 were negative for OSNA-MesLNM, and negative p-LatLNM was confirmed in all cases. The point estimate of the NPV was 100%, with the 95% confidence interval ranging from 79.4% to 100.0%. The OSNA method is useful in selecting patients in whom LatLND can be omitted in real-world clinical practice.


Cement- and screw-retained implant-supported prostheses: up to 10 years of follow-up of a new design.
This retrospective study investigated treatment outcomes over 10 years of a new prosthesis design in implant prosthodontics that uses a combined cement- and screw-retained principle. The clinical data of 78 implant-supported prostheses were examined. Each prosthesis incorporated at least 1 screw-retained element and 1 or more cement-retained telescopic units. One hundred twenty-four screw-retained and 161 cement-retained abutments were employed. Of the 286 implants placed, 5 were lost prior to prosthetic loading and 4 (1.4%) were lost approximately 14 months after loading. Eight (2.8%) abutment screws were retightened and 1 gold prosthetic screw was replaced after 1,372 days following fracture. No accidental dislodgment of any prosthesis occurred. The introduction of a screw retainer into a series of cement retainers permitted the use of weak cement on the telescopic abutments. This facilitated removal when required while preventing accidental dislodgment. Improved equipment and the learning curve decreased the incidence of abutment screw loosening with time. The ease of retrievability, allied with the security of seating and excellent appearance, makes the combined screw- and cement-retained prosthesis valuable in implant prosthodontics.


Activity of bone morphogenetic protein-7 after treatment at various temperatures: freezing vs. pasteurization vs. allograft.
Insufficient bone union is the occasional complication of biomechanical reconstruction after malignant bone tumor resection using temperature treated tumor bearing bone; freezing, pasteurization, and autoclaving. Since bone morphogenetic protein (BMP) plays an important role in bone formation, we assessed the amount and activity of BMP preserved after several temperature treatments, including -196 and -73°C for 20 min, 60 and 100°C for 30 min, 60°C for 10h following -80°C for 12h as an allograft model, and 4°C as the control. The material extracted from the human femoral bone was treated, and the amount of BMP-7 was analyzed using an enzyme-linked immunosorbent assay. Then, the activity of recombinant human BMP-7 after the treatment was assessed using a bioassay with NIH3T3 cells and immunoblotting analysis to measure the amount of phospho-Smad, one of the signaling substrates that reflect the intracellular reaction of BMPs. Both experiments revealed that BMP-7 was significantly better preserved in the hypothermia groups. The percentages of the amount of BMP-7 in which the control group was set at 100% were 114%, 108%, 70%, 49%, and 53% in the -196, -73, 60, 100°C, and the allograft-model group, respectively. The percentages of the amount of phospho-Smad were 89%, 87%, 24%, 4.9%, and 14% in the -196, -73, 60, 100°C, and the allograft-model group, respectively. These results suggested that freezing possibly preserves osteoinductive ability than hyperthermia treatment.


Testosterone and gonadotropins but not estrogen associated with spatial ability in women suffering from schizophrenia: a double-blind, placebo-controlled study.
The aim of this study was to investigate the association between estrogen and spatial ability tasks in women suffering from schizophrenia. For this purpose, a placebo-controlled, double-blind, three-time cross-over study using 17beta-estradiol combined with norethisterone acetate for replacement therapy and as an adjunct to a naturalistic maintenance antipsychotic treatment was carried out over a period of 8 months. Nineteen women (mean age=38.0 years, SD=9.9 years) with schizophrenia hospitalized for the first time or repeatedly were included in the study. Sex hormones - 17beta-estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, testosterone, and dehydroepiandrosterone sulfate - were measured and the patients completed a neuropsychological test in the last two active drug and/or placebo phases. Three different spatial ability tasks - spatial orientation, spatial visualization, and flexibility of closure - were measured by a paper-and-pencil test. No association between estrogen and spatial ability was found; however, in an additional exploratory data analysis, high levels of testosterone, LH, and FSH correlated significantly with performance in the flexibility of closure task. This is the very first study, based on estrogen intervention instead of physiological hormone changes, to examine the association between estrogen and spatial ability in women with schizophrenia.


Lung involvement in children with newly diagnosed rheumatic diseases: characteristics and associations.
Pulmonary complications of rheumatic diseases may cause functional impairment and increase mortality. However, reports regarding detection of lung involvement in children with treatment-naive, newly diagnosed rheumatic diseases are scarce. Herein, we aimed to describe the characteristics of such patients and explore the association between lung involvement and rheumatic disease. From January 2019 to June 2021, 48 pediatric patients with treatment-naive, newly diagnosed rheumatic diseases at Department of Rheumatology and Immunology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University were included with pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) findings, and 51 age-matched healthy controls were examined based on PFTs. Univariate and multivariable logistic regression analyses were used to investigate the clinical characters and laboratory parameters associated with lung involvement in these patients. Asymptomatic patients had a faster respiratory rate and a higher ratio of forced expiratory volume in 1 s/forced vital capacity than the controls (P < 0.05). More patients than controls were observed to have a decreased DLCO below the lower limit of normal (18 of 45 [40.0%] vs. 6 of 36, respectively; P = 0.041). Among the 48 patients, 8 (16.7%) had abnormal HRCT findings and 27 (56.3%) had abnormal PFT results. Thirty-one (64.6%) patients had lung involvement. Logistic regression revealed that increases in the erythrocyte sedimentation rate (ESR) and CD4/CD8 ratio were associated with increased odds ratio of lung involvement (1.037, 95% CI: 1.003-1.072; 9.875, 95% CI: 1.296-75.243, respectively). Pediatric patients with treatment-naive, newly diagnosed rheumatic diseases are prone to pulmonary involvement. Increased ESR and CD4/CD8 are associated with elevated odds of lung involvement in patients. We recommend routine pulmonary evaluation in such patients, especially in high-risk patients, even in the absence of respiratory symptoms, once they are diagnosed with rheumatic disease.


Nuclear Trapping through Inhibition of Exosomal Export by Indomethacin Increases Cytostatic Efficacy of Doxorubicin and Pixantrone.
Although R-CHOP-based immunochemotherapy cures significant proportions of patients with aggressive B-cell lymphoma, tumor cell susceptibility to chemotherapy varies, with mostly fatal outcome in cases of resistant disease. We and others have shown before that export of cytostatic drugs contributes to drug resistance. Now we provide a novel approach to overcome exosome-mediated drug resistance in aggressive B-cell lymphomas. We used well-established centrifugation protocols to purify exosomes from DLBCL cell lines and detected anthracyclines using FACS and HPLC. We used shRNA knockdown of ABCA3 to determine ABCA3 dependence of chemotherapy susceptibility and monitored ABCA3 expression after indomethacin treatment using qPCR. Finally, we established an in vivo assay using a chorioallantoic membrane (CAM) assay to determine the synergy of anthracycline and indomethacin treatment. We show increased efficacy of the anthracycline doxorubicin and the anthracenedione pixantrone by suppression of exosomal drug resistance with indomethacin. B-cell lymphoma cells in vitro efficiently extruded doxorubicin and pixantrone, in part compacted in exosomes. Exosomal biogenesis was critically dependent on the expression of the ATP-transporter A3 (ABCA3). Genetic or chemical depletion of ABCA3 augmented intracellular retention of both drugs and shifted the subcellular drug accumulation to prolonged nuclear retention. Indomethacin increased the cytostatic efficacy of both drugs against DLBCL cell lines in vitro and in vivo in a CAM assay. We propose pretreatment with indomethacin toward enhanced antitumor efficacy of anthracyclines and anthracenediones.


Effects of paraquat on the green alga Dunaliella salina: protection by the mimic of superoxide dismutase, Desferal-Mn(IV).
Paraquat caused a time-, dose-, and light-dependent bleaching of the halophilic green alga Dunaliella salina. Sublethal levels of paraquat elicited increases in cell content of both superoxide dismutase and catalase, with changes in the pattern of electromorphs of these enzymes. Desferal-Mn(IV), which catalyzes the dismutation of O2- in vitro, protected against the toxic effect of paraquat. Desferal (desferoxamine mesylate) alone was toxic to D. salina, and the salts of Mn(II), Mn(III), and Mn(IV), in the absence of Desferal, did not protect. Desferal-Mn(IV) is green, but its absorbance was 15% or less than the peak absorbances due to the chlorophyll in D. salina under the conditions of exposure; hence, masking of incident light could not have been the basis of the protective effect of the complex. Incubation of the cells with Desferal-Mn(IV), for up to 8 h prior to the addition of paraquat, did not increase its protective action, and brief washing, following 30 min incubation with the complex, eliminated its protective effect. Neither catalase nor superoxide dismutase, added to the medium, provided protection against paraquat. These results support the view that Desferal-Mn(IV) gains entry into D. salina and protects against the lethal effect of paraquat by there catalyzing the dismutation of O2- into H2O2 + O2.


Effect of anti-nerve growth factor treatment on pituitary adenylate cyclase activating polypeptide expression in adult sensory neurons exposed to adjuvant induced inflammation.
Expression of pituitary adenylate cyclase activating polypeptide (PACAP) is increased in sensory neurons exposed to adjuvant induced peripheral inflammation. Local elevation in expression of the neurotrophin nerve growth factor (NGF) is a main factor contributing to the neuronal response to inflammation. This study examines the role of endogenous NGF in inflammation-associated increases in PACAP expression using the adjuvant-induced peripheral inflammation model with or without systemic administration of antibodies against NGF. Quantitative in situ hybridization was used to detect changes in neuronal PACAP mRNA expression and to correlate this expression with neuronal mRNA expression of the NGF receptor tyrosine kinase (trk) A. The results from this study show that inflammation triggered increases in PACAP expression occurs in small- to medium-sized dorsal root ganglion (DRG) neurons that also express trkA, and that this elevation in PACAP expression is prevented by systemic injection of anti-NGF. This supports a role for NGF as a positive regulator of PACAP expression during inflammation.


Effects of (artificial) boar stimuli on uterine activity in estrous sows.
This study aims to examine influences of specific boar stimuli on uterine activity in estrous sows, by comparing uterine activity in presence of a mature teaser boar and a robot boar with variable stimuli. Nineteen multiparous, cyclic, commercial crossbred sows were used. Intra-luminal uterine pressure was measured using a non-surgical method for 45 min before applying one of four treatments in combination with a back-pressure-test (BPT): (1) robot with olfactory and auditory stimuli (R+O+A) (n=16), (2) robot with auditory stimuli (R+A) (n=16), (3) robot without additional stimuli (R) (n=16), (4) a mature boar (boar) (n=15). After treatment, measurements continued for 30 min. For each measurement, frequency, mean amplitude and mean duration of uterine contractions were determined. Spontaneous frequency of uterine contractions was 18.6+/-0.7 h(-1) on average and did not differ between treatments. Frequency of contractions increased significantly for the boar (+5.6+/-1.3 h(-1); P<0.01), R+O+A (+3.9+/-1.3; P<0.01) and R+A (+2.6+/-1.3; P<0.05). The effect of boar presence on frequency of contractions was greater than the effect of R (P<0.05). Amplitude and duration of contractions were not affected by treatment. The change in frequency was dependent on spontaneous frequency (P<0.01). In conclusion, the higher the level of boar stimuli, the greater the increase in frequency of uterine contractions. The results indicate that the used combinations of artificial boar stimuli do not mimic a 'whole' boar. It is unclear which boar stimuli stimulate maximal uterine activity during estrus.


Examination of behavioral deficits triggered by targeting Bdnf in fetal or postnatal brains of mice.
Human and animal studies have implicated brain-derived neurotrophic factor (BDNF) in the etiology of psychiatric disorders. It is expressed in limbic regions of the brain associated with the regulation of emotionality during fetal development and in the adult animal. To further our understanding of the role of BDNF in the modulation of mood and to distinguish its prenatal and postnatal functions, we investigated and contrasted behavioral changes elicited by its depletion from fetal or postnatal brains of mice. Two corresponding lines of BDNF conditional knockout mice were subjected to a battery of behavioral tests assessing locomotor, depressive, aggressive and anxiety-related behaviors. We found that both lines of mutants were dramatically hyperactive during the light and dark cycles and hyperaggressive. They also exhibited a depression-like phenotype in the tail suspension test but not in the forced swim test. Interestingly, depletion of BDNF from the fetal brain had more pronounced effects on aggressive and depressive-like behaviors and led to deficits in 5-HT(2A) receptor content in the medial frontal cortex, highlighting the importance of this neurotrophin during development. We conclude that expression of BDNF both pre- and postnatally is essential for normal modulation of behavior by neural circuits in the adult animal.


Psychosocial factors and quality of life in children and adolescents with implantable cardioverter-defibrillators.
Few data exist on the quality of life in children and adolescents with implantable cardioverter-defibrillators (ICDs). The objective of this study was to determine whether anxiety, depression, family functioning, and quality of life are related to cardiac illness severity in pediatric patients with ICDs. The subjects were 20 patients (mean age 14.8 years; median 15.1, range 9 to 19) who had an ICD implantation a mean 1.4 years (median 0.1, range 0 to 6) before the study. The patients completed the Revised Children's Manifest Anxiety Scale, Reynold's Adolescent/Child Depression Scales, Child Health Questionnaire-87, and the Worries About ICDs Scale. The parents completed the Impact-on-Family Scale and the Child Health Questionnaire (CHQ-50). The Defibrillator Severity Index assessed cardiac severity. The rates of anxiety or depression were not increased, although the patients appeared to experience a greater need for social acceptance. Parent ratings of overall family functioning did not differ significantly from normative sample means. Parents reported significantly lower CHQ-50 summary physical functioning scores than scores of a normative United States sample, whereas there was no significant difference for the CHQ-50 summary psychosocial score. Caregivers perceived that their children had a lower quality of life when asked about their child's physical functioning, functioning in the social-physical role, and general health perceptions. Despite the overall nonsignificance of the psychosocial summary score, the social emotional/behavioral role, and the emotional impact their child's health had on themselves, subscales were all significantly lower than the normative sample. Cardiac illness severity was not significantly associated with anxiety, depression, quality of life, or family functioning. However, significant associations were found among measures of anxiety, depression, family functioning, and quality of life. Overall, most pediatric patients with ICDs appear to be a resilient group of youngsters. Their quality of life was more strongly correlated with their feelings of anxiety and depression as well as their family functioning than to the severity of their cardiac illness.


Linguistic description in nonfluent dysphasia: utilization of pictograms.
Nonfluent dysphasic utterances for pictogram or sequential picture descriptions were compared against those elicited in a standard stative single-picture description task. Elicited utterances were also compared to identify the availability of different variables within phonologic, syntactic, and semantic levels. Descriptive data revealed that Pictograms yielded a relatively greater frequency of occurrence for the variables examined under the parameters of phonology, syntax, and semantics. Of the different variables examined for each parameter, a significantly greater incidence of phonemic paraphasias than neologistic paraphasias were obtained for the parameter of phonology. For the parameter of syntax, significantly more verb phrases were in error than noun phrases; and significantly more syntactic complexity levels 1 and 3 were produced than were levels 2, 4, or 5. Data for the parameter of semantics revealed a significantly greater occurrence of hesitations than circumlocutions, verbal paraphasias, or revisions. Discussion of the obtained findings relate to language assessment and linguistic characterization of nonfluent dysphasia.


Chemogenomics and biotechnology.
A robust knowledge of the interactions between small molecules and specific proteins aids the development of new biotechnological tools and the identification of new drug targets, and can lead to specific biological insights. Such knowledge can be obtained through chemogenomic screens. In these screens, each small molecule from a chemical library is applied to each cell type from a library of cells, and the resulting phenotypes are recorded. Chemogenomic screens have recently become very common and will continue to generate large amounts of data. The interpretation of this data will occupy biologists and chemists alike for some time to come. This review discusses methods for the acquisition and interpretation of chemogenomic data, in addition to possible applications of chemogenomics in biotechnology.


Thinking about Trust: People, Process, and Place.
This brief paper is about trust. It explores the phenomenon from various angles, with the implicit assumptions that trust can be measured in some ways, that trust can be compared and rated, and that trust is of worth when we consider entities from data, through artificial intelligences, to humans, with side trips along the way to animals. It explores trust systems and trust empowerment as opposed to trust enforcement, the creation of trust models, applications of trust, and the reasons why trust is of worth.


Chelidonium majus and its effects on uterine contractility in a perfusion model.
The herbal agent celandine is thought to have mainly spasmolytic effects, but in the uterus it is regarded as promoting contractions, which can offer promising and innovative options for optimizing artificial reproduction. The aim of the present study was to investigate the effect of celandine on the uterine muscle, using a perfusion model of swine uteri. Sixteen swine uteri were perfused with Krebs-Ringer solution. Celandine (Chelidonium, Paverysat; Johannes Bürger Ysatfabrik Ltd., Bad Harzburg, Germany) was administered at increasing dosages. Intrauterine pressure (IUP) was recorded using an intrauterine double-chip microcatheter (Urobar 8 DS-F, Raumedic, Rehau AG & Co., Rehau, Germany). Differences in pressure (ΔP) and area under the curve (ΔAUC) after drug administration in the uterine body and uterine horn in the various dilution series were noted. A paired Student's t-test was used to evaluate differences between groups, with significance set at P<0.05. A significant initial increase in uterine activity was visible at each dosage. Inhibition of uterine activity was seen over longer periods of 5 and 10 min, particularly for a medium-dose range of 1-2mg/ml. At a dosage of 2mg/ml in particular, celandine almost always led to significant values. Following intra-arterial administration in a swine uterus perfusion model, celandine initially causes a significant increase in contractility, which is followed over time by a relaxation phase. This suggests interesting hypotheses on whether Chelidonium majus might be used to promote targeted sperm transport.


Electrical half-wave rectification at ferroelectric domain walls.
Domain walls in ferroelectric semiconductors show promise as multifunctional two-dimensional elements for next-generation nanotechnology. Electric fields, for example, can control the direct-current resistance and reversibly switch between insulating and conductive domain-wall states, enabling elementary electronic devices such as gates and transistors. To facilitate electrical signal processing and transformation at the domain-wall level, however, an expansion into the realm of alternating-current technology is required. Here, we demonstrate diode-like alternating-to-direct current conversion based on neutral ferroelectric domain walls in ErMnO3. By combining scanning probe and dielectric spectroscopy, we show that the rectification occurs at the tip-wall contact for frequencies at which the walls are effectively pinned. Using density functional theory, we attribute the responsible transport behaviour at the neutral walls to an accumulation of oxygen defects. The practical frequency regime and magnitude of the direct current output are controlled by the bulk conductivity, establishing electrode-wall junctions as versatile atomic-scale diodes.


Options for the treatment of serious infections with interleukin-1.
In this paper, the effects of recombinant human interleukin-1 (IL-1) on non-specific resistance to infection are reviewed. In experiments in neutropenic mice, a single injection of a low dose of IL-1 (8-800 ng) appears to protect against death from lethal Pseudomonas aeruginosa and Candida albicans infections. In non-neutropenic mice protection can also be obtained with such dosages of IL-1 in infection caused by Klebsiella pneumoniae or Listeria monocytogenes. Low dosages of IL-1 are also able to prevent lethal cerebral malaria in mice. No effect has been found in murine cytomegalovirus infection. With the exception of C. albicans infection and malaria, protection is only obtained if IL-1 is given before the infection. The mechanism of protection has not been elucidated; in the Pseudomonas and Klebsiella infection, it could be demonstrated that survival was not due to a direct antibacterial effect of IL-1, not due to the action of granulocytes or increased hematopoietic recovery and not due to activation of macrophages and increased bactericidal mechanisms. In the experimental Listeria infection however, animals treated with IL-1 had lower bacterial counts in their organs. Since the cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF) are much less potent than IL-1 in these protection experiments, it is very unlikely that they are endogenous mediators of the protection induced by IL-1. The effect is not mediated via the cyclooxygenase pathway, since premedication with ibuprofen does not influence the protective effect of IL-1. Taking these data together, it is felt that IL-1 holds promise as a therapeutic agent in humans.


Perineal desquamation: An early sign of the Kawasaki disease phenotype of MIS-C.
Multisystem inflammatory syndrome in children (MIS-C) is a syndrome associated with coronavirus disease 2019. Various phenotypes of MIS-C have been described including Kawasaki disease (KD). Although perineal desquamation is a known early sign of KD, to our knowledge, this rash has not yet been described in the KD phenotype of MIS-C. In this article, we report two patients in whom perineal desquamation was an early clue for the KD phenotype of MIS-C.


Novel treatment of patients with lower extremity ischemia: use of percutaneous atherectomy in 579 lesions.
Endovascular options for the treatment of lower extremity peripheral arterial disease are typified with diminished patency. A novel alternative to standard angioplasty and stent is the excision of the obstructing arterial plaque using a minimally invasive technique, the Silverhawk Atherectomy device. A prospective database was maintained of SilverHawk procedures from 2004 to 2007. A total of 579 lesions were treated in 275 patients (claudication 101 patients (36.7%) and critical limb ischemia (CLI) in 174 patients (63.3%). Noninvasive laboratory evaluation was performed at 1, 3, and 6 months, and yearly. Stand-alone atherectomy was attempted, and adjunct therapy was used for residual stenosis. Mean age was 70.0 years (range, 37-102) (62.5% male, 46.2% smokers, 67.6% diabetes mellitus). Lesion characteristics were 199 superficial femoral arteries, 110 popliteal, 218 tibials, and 52 multilevel. Thirty-day perioperative mortality was 1.8%. Mean follow-up was 12.5 months (range, 0.5-48.2). 18-month primary and secondary patency for all lesions was 52.7% +/- 2.8 and 75.0% +/- 2.4 (P < 0.0001). Eighteen-month primary and secondary patency for claudicants was 58.0% +/- 4.3 and 82.5% +/- 3.5 (P < 0.0001) and for CLI was 49.4% +/- 3.7 and 69.9% +/- 3.2 (P < 0.0001), respectively. The reintervention rate was 25.3% in claudicants and 30.1% for CLI. Limb salvage was 100% in claudicants and overall limb salvage was 92.4% per patient at 18 months and only 4.4% required bypass. This is the largest reported series with the longest follow-up showing the SilverHawk device as an effective endovascular therapy for patients with claudication and CLI with a low mortality, low complications rate, low amputation rate, and rare need for conversion to surgical bypass. The majority of reintervention was performed with endovascular techniques.


A pilot study of potassium supplementation in the treatment of hypokalemic patients with rheumatoid arthritis: a randomized, double-blinded, placebo-controlled trial.
Patients with rheumatoid arthritis (RA) have been described as having significantly low serum potassium concentrations than that in healthy subjects. We assessed the therapeutic efficacy and tolerability of oral potassium supplement dissolved in grape juice in female hypokalemic patients with active RA. Thirty-two hypokalemic patients with active RA were investigated in a parallel, randomized design. In addition to their usual medication, the control group received placebo and the intervention group received 6000 mg chloride potassium dissolved in grape juice on 28 consecutive days. The primary outcome parameter was the change of pain on a visual analog scale (VAS). The American College of Rheumatology (ACR) percent response criteria and Disease Activity Score 28 (DAS28, 28-joint count) and the European League Against Rheumatism (EULAR) moderate response were assessed. Mean age was 48.6 +/- 6 years. In the potassium group, 43.75% (7/16) of the patients met the criteria of 33% lower pain intensity compared with 6.25% (1/16) in the placebo group (P < .02) at day 28. Also, 31.25% (5/16) of the patients in the intervention group achieved moderate responses, according to the EULAR criteria. The corresponding percentage for patients receiving placebo was 6.25% (1/16) (P < .05). Potassium supplements appeared to decrease pain intensity. This article reports a trial evaluating the effect of potassium supplementation in the treatment of pain in hypokalemic patients with rheumatoid arthritis. The elevated serum cortisol and potassium values in the treatment group correlate negatively with patient's assessment of pain intensity, reflecting an anti-pain effect for potassium supplementation.


Addressing language barriers: building response capacity for a changing nation.
The absence of universally available language services is a national healthcare system failure, the burden of which is suffered by patients with limited English proficiency and their healthcare providers. Conceptualizing mandatory provision of language access as an unfair, unfunded mandate ignores massive and fundamental social changes taking place. Overcoming language barriers is essential to safe, quality health care. This paper, informed by the experience of Hablamos Juntos, a national demonstration project funded by the Robert Wood Johnson Foundation, argues that national and health industry investments are needed to develop population-based approaches supported by communication and information technology, and that these investments may prove useful to improving healthcare communication for English-speaking patients as well.


Molecular cloning and heterologous expression of a laccase gene from Pleurotus eryngii in free and immobilized Saccharomyces cerevisiae cells.
A full length cDNA encoding an extracellular laccase was isolated by reverse transcription polymerase chain reaction from the mycelia of the mushroom Pleurotus eryngii. The isolated sequence, denoted Ery3, encodes for a mature laccase isoenzyme of 531 amino acid residues with a predicted molecular weight of 56.6 kDa. All sequence motifs, being the signature sequences used to identify the laccases, were found in the Ery3 protein sequence. The Ery3 cDNA was expressed in Saccharomyces cerevisiae and the effects of copper concentration and cultivation temperature were investigated. S. cerevisiae cells were immobilized in calcium alginate gel and the optimal immobilization parameters for the enhanced production of laccase were determined. The immobilization was most effective with 3% sodium alginate, 0.1 M calcium chloride and an initial biomass of 4.5 x 10(8) cells. The enzyme yield obtained with immobilized cells (139 mU ml(-1)) showed a 1.6-fold increase compared to the highest yield obtained with free cells. The alginate beads showed good stability and retained 84% capacity of enzyme production after seven repeated cycles of batch fermentation. The immobilization system proved to increase the proteolytic stability of the recombinant Ery3 protein. To our knowledge, this is the first report on S. cerevisiae whole-cell immobilization for recombinant laccase production.