Clonal evolution of glioblastoma under therapy.
Glioblastoma (GBM) is the most common and aggressive primary brain tumor. To better understand how GBM evolves, we analyzed longitudinal genomic and transcriptomic data from 114 patients. The analysis shows a highly branched evolutionary pattern in which 63% of patients experience expression-based subtype changes. The branching pattern, together with estimates of evolutionary rate, suggests that relapse-associated clones typically existed years before diagnosis. Fifteen percent of tumors present hypermutation at relapse in highly expressed genes, with a clear mutational signature. We find that 11% of recurrence tumors harbor mutations in LTBP4, which encodes a protein binding to TGF-β. Silencing LTBP4 in GBM cells leads to suppression of TGF-β activity and decreased cell proliferation. In recurrent GBM with wild-type IDH1, high LTBP4 expression is associated with worse prognosis, highlighting the TGF-β pathway as a potential therapeutic target in GBM.


Cell commitment and gene expression in the axolotl embryo.
In the axolotl embryo the somitic mesoderm passes through a reversible and then an irreversible phase of commitment with respect to its later differentiation into muscle. We show that the commencement of alpha-actin synthesis and the first appearance of thin myofilaments occur at the the same developmental stage as the transition between these phases. In intact embryos beta-and gamma-actin are made at all stages of development and in all tissues. alpha-actin, however, first appears at the late head process stage and is confined to the somites and tailbud, the regions of the embryo which later form the myotomal muscles. The thin filaments first appear near the myocoel of the somites in association with a novel organelle of mottled appearance and are quite distinct in structure from the epidermal microfilament networks found in embryos of the same stage. Cell fusion occurs somewhat later, although before the appearance of muscle striations in the light microscope. Well formed sarcomeres are not found until some time after the onset of motility. Presumptive somitic mesoderm isolated at a stage before the transition and cultured in a buffered salt solution for six days autonomously begins to synthesize alpha-actin and develop sarcomeres with the normal structure.


Development of novel montmorillonite-based sustained release system for oral bromopride delivery.
The drug delivery systems are an important strategy of pharmaceutical technology to modulate undesirable properties, increasing efficacy, and reducing the side effects of active pharmaceutical ingredients (API). The sustained release is a type of controlled-release system that provides a suitable drug level in the blood through a slow release rate. An interesting alternative to achieve a controlled release is the application of carrier materials such as polymers, cyclodextrins, and clays. Sodium montmorillonite (Na-MMT) is a biocompatible natural clay that allows the insertion of organic compounds in interlamellar space, owing to its high cation exchange capacity and large internal surface area. Bromopride (BPD) is an aminated compound with antiemetic properties classified as class II (low solubility, high permeability) of the Biopharmaceutical Classification System (BCS). Herein, the aim of the study was the development and investigation of a drug delivery system formed by intercalation of BPD with Na-MMT. The results indicate the successful intercalation of this API with the lamellar silicate, meanwhile, there was no evidence of BPD intercalation in organic montmorillonite. The Na-MMT/BPD molecular complex exhibits a sustained release in performed assays. Molecular dynamics simulations suggested that BPD molecules interact with the montmorillonite layer through ion-dipole interactions and also between BPD molecules, forming hydrogen bonds web into montmorillonite interlayer space. The new drug delivery system showed an alternative to achieve the BPD sustained release, which may improve its pharmacological performance in therapeutic applications.


Accessibility control of variable region gene assembly during T-cell development.
T-cell development is a complex and ordered process that is regulated in part by the progressive assembly and expression of antigen receptor genes. T cells can be divided into two lineages based on expression of either an alpha beta or gamma delta T-cell antigen receptor (TCR). The genes that encode the TCR beta and gamma chains lie in distinct loci, whereas the genes that encode the TCR alpha and delta chains lie in a single locus (TCR alpha/delta locus). Assembly of TCR variable region genes is mediated by a site-specific recombination process that is common among all lymphocytes. Despite the common nature of this process, recombination of TCR genes is tightly regulated within the context of the developing T cell. TCR beta, gamma and delta variable region genes are assembled prior to TCR alpha variable region genes. Furthermore, assembly of TCR beta variable region genes is regulated within the context of allelic exclusion. The regulation of rearrangement and expression of genes within the TCR alpha/delta locus presents a complicated problem. TCR alpha and delta variable region genes are assembled at different stages of T-cell development, and fully assembled TCR alpha and delta variable region genes must be expressed in distinct lineages of T cells, alpha beta and gamma delta, respectively. We have developed several experimental approaches to assess the role of cis-acting elements in regulating recombination and expression of TCR genes. Here we describe these approaches and discuss our analyses of the regulation of accessibility of the TCR beta and TCR alpha/delta loci during T-cell development.


Windrow co-composting of natural casings waste with sheep manure and dead leaves.
After studying the waste management opportunities in small and medium companies of natural casings, composting has proved more viable and cost effective solution for the valorization of these types of waste, but its feasibility depends on the final product value. This paper investigated a pilot scale program for the windrow co-composting of natural casings waste with sheep manure and dead leaves incorporation. Processing, characterization and application of the final compost were described and the final compost was analyzed for pathogens, metals, nutrients, maturity, and agronomic parameters. The results showed that all test result levels were below the limits specified in the EPA regulations published in Title 40, Section 503, of the Code of Federal Regulations (40 CFR 503). Moreover, the agronomic value tests which include nutrients, organic matter, pH, electrical conductivity, etc. showed that the compost had high organic-matter content and low salt content, all of which indicate good compost characteristics. The ratio of nitrogen (N), phosphorus (P), and potassium (K), or NPK ratio, was measured at 1.6-0.9-0.7. Reported units are consistent with those found on fertilizer formulations.


Periodontal status, perceived stress, diabetes mellitus and oral hygiene care on quality of life: a structural equation modelling analysis.
To determine if periodontal risk assessment (PRA), the number of missing teeth, diabetes mellitus (DM), perceived stress and interproximal cleaning are associated with oral health-related quality of life (OHRQoL), using Andersen's behavioral modelling (ABM). Data derived from 472 adults derived from a representative population of the Study of Periodontal Health in Almada-Seixal (SoPHiAS) was used. Socioeconomic status, perceived stress scale (PSS-10), oral health behaviors and oral health impact profile (OHIP-14) were collected through questionnaire. Periodontal conditions were assessed with a full-mouth periodontal examination. PRA was computed through behavioral and clinical information. Variables were grouped into Predisposing Factors, Enabling, Need, Oral Health Behaviors and Perceived Health Outcome latent variables. Confirmatory factor analysis, structural ABM and model fitness were conducted. ABM applied to OHIP-14 showed acceptable model fit (χ2 = 2.75, CFI = 0.92, TLI = 0.90, RMSEA = 0.05, CI 90% [0.04-0.07]). The average of OHRQoL was 9.5 ± 11.3. Patient with periodontitis and with a high number of missing teeth experienced worse OHRQoL. Uncontrolled DM participants had more periodontal treatment necessity and poorer OHRQoL. Characteristic like aging and lower levels of education were directly associated with better OHRQoL, but in indirect path the OHRQoL was diminishes. Good oral hygiene and preventative measures were associated to lower periodontal treatment necessity. Lower periodontal treatment necessity was associated to higher OHRQoL. Age, tooth loss and interproximal cleaning were the most associated items to Predisposing, Need and Oral Health Behaviors, respectively. ABM confirmed age, number of missing teeth, DM, interproximal cleaning and perceived stress as associated factors for OHRQoL. Uncontrolled DM was associated to higher Need and poorer OHRQoL. Good oral hygiene habits promote a healthy periodontium and, consequently, increases OHRQoL.


Erratum: Mina, R.; et al. Minimal Residual Disease in Multiple Myeloma: State of the Art and Future Perspectives. J. Clin. Med. 2020, 9, 2142.
The authors sincerely apologize for the inaccuracies made during the revision that a product line has been associated with the wrong company [...].


Repeated percutaneous hepatic perfusion with melphalan can maintain long-term response in patients with liver cancers.
Chemosaturation (CS; CHEMOSAT®, Delcath Systems Inc.) temporarily administers melphalan into the liver by percutaneous hepatic perfusion (PHP). CS-PHP can effectively control growth in liver tumors, but efficacy and tolerability of sequential treatments are unclear. We analyzed outcomes of sequential CS-PHP treatment. Patients with either unresectable intrahepatic metastases of ocular melanoma (OM, n = 9), cholangiocarcinoma (CCA, n = 3), or hepatocellular carcinoma (HCC, n = 1) were recruited retrospectively. Response was assessed by tomography imaging. Ten patients (mean age 60 years) with more than one CS-PHP treatment were included. CS-PHP was administered 2-6 times in the OM patients, 3 times in the CCA, and the HCC patient received 6 treatments. Overall response rate (ORR) to CS-PHP was 80%, and stable disease was achieved in one patient. Median hepatic progression-free survival (hPFS) was 336 days (range 0-354) for OM, 251 days for the CCA patient, and 256 days for the HCC patient. At the end of observation (153-701 days after first CS-PHP), 6/10 patients were still alive (5/9 with OM, 0 with CCA, and 1 with HCC). Death cases were not related to CS-PHP. Adverse events were mostly hematologic, grade I-IV, and self-resolving. The liver function was not deteriorated by CS-PHP. We conclude that repeated CS-PHP treatments were effective and well tolerated in the long term.


Pesticide residues in Rita rita and Cyprinus carpio from river Ganga, India, and assessment of human health risk.
Present study was carried out to determine the concentration and bioaccumulation of pesticide residues in two commonly edible fishes: bagrid fish, Rita rita and common carp, Cyprinus carpio collected from river Ganga at Narora, India. The human health risk via consumption of these fishes was also assessed. The n-hexane extract of the muscle tissues was characterized by gas chromatography coupled to mass spectrometry and quantified by electron capture detector for pesticide residues. Bioaccumulation factor (BAF) in bagrid fish for detected pesticides was found to be higher than those in common carp. Estimated daily intake (EDI) values in our study were insignificantly higher than Average daily intake (ADI) values. Target hazard quotient (THQ) via consumption of selected fishes was found to be lower than the set 1.0, inferring non-carcinogenic risk. With regard to contaminants carcinogenic effects the total risk ratio (R) values of each pesticide was found lower than threshold risk limit except of heptachlor which indicates carcinogenic risk. The results justify pesticide pollution in river Ganga at Narora and thus more attention is required in order to help improve the health status of this ecosystem and reduce contamination of fishes.


Phytochemical Extract from Carica papaya Leaves and Punica granatum Seeds as Therapy Against Cognitive Impairment in a Murine Model.
Mild cognitive impairment (MCI) is defined as inter-stage between normal cognitive aging and major neurocognitive disorder (MND). This state of decay is a crucial factor in treatment to prevent the progression to MND. In this study, our group developed a virtual screening process to evaluate 2568 phytochemical compounds against 5 key proteins associated with MCI and MND. As a result, two potential candidates were identified: carpaine, found in Carica papaya leaves, and punicalagin, present in Punica granatum. A model of cognitive impairment (CI) was developed in 10-month-old male Sprague Dawley rats by administering aluminum chloride (AlCl3) at a dose of 100 mg/kg/day for 30 days. After AlCl3 administration period, one of the groups received carpaine and punicalagin in a phytochemical extract (PE) by oral gavage for 30 days. Novel object recognition test (NOR) was assessed at three different time points (T1 - before CI, T2 - after CI, and T3 - after PE treatment). Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were identified in the hippocampus of rats at the end of the study period. After administration of AlCl3, a reduction in discrimination index vs control rats (CI = 0.012 ± 0.08 vs Control = 0.076 ± 0.03), was observed. After phytochemical extract treatment, a significant increase in discrimination index values was observed in the PE group 0.4643 ± 0.13 vs CI group 0.012 ± 0.08. Additionally, the evaluation of immunohistochemistry showed an increase in GFAP positivity in the hippocampus of the CI groups, while a slight decrease was observed in the PE group. This work addressed a comprehensive methodology that utilized in silico tools to identify phytochemical compounds (carpaine and punicalagin) as potential candidates for affecting key proteins in CI. The phytochemical extract containing carpaine and punicalagin resulted in a trend in the decrease of GFAP expression in the hippocampus and improved recognition memory in rats with CI induced by age and AlCl3 administration.


Possible lymphocyte effects on lactase expression by mouse jejunal enterocytes.
Jejunal intraepithelial lymphocyte numbers fall and lactase activity increases during early infection with the intestinal parasite Nematospiroides dubius. Both these variables later return to values found in control mice. These results support the view that local immune reactions, suppressed by the presence of N. dubius, normally inhibit lactase expression by mouse enterocytes.


The efficiency of human reproduction after in vitro fertilization and embryo transfer.
Two hundred ninety-seven nonpregnant patients were used to study the possibility of early transient implantation as a parameter of the efficiency of in vitro fertilization (IVF) procedures. Ten patients without embryo transfer (ET) were used as controls. The luteal estradiol, progesterone, and human chorionic gonadotropin were measured by radioimmunoassay (RIA). In 31 cases, a transient elevation of hCG occurred after complete serum clearance of exogenous hCG, suggesting that the transient increase in hCG was of embryonic origin. In addition, five patients were found to have prolonged clearance of hCG, which was due not to individual variation in clearance, but to a minimal production of hCG by trophoblastic tissue. These data suggest that implantations occurred in 12.1% of our so-called "nonpregnant" patients.


Drug Treatment of Epilepsy Neuropsychiatric Comorbidities in Children.
There is increasing recognition that epilepsy can be associated with a broad spectrum of comorbidities. While epileptic seizures are an essential element of epilepsy in children, there is a spectrum of neurological, mental health and cognitive disorders that add to the disease burden of childhood epilepsy resulting in a decreased quality of life. The most common comorbid conditions in childhood epilepsy include depression, anxiety, autism spectrum disorders, sleep disorders, attention deficits, cognitive impairment, and migraine. While epilepsy can result in comorbidities, many of the comorbidities of childhood have a bi-directional association, with the comorbid condition increasing risk for epilepsy and epilepsy increasing the risk for the comorbid condition. The bidirectional feature of epilepsy and the comorbidities suggest a common underlying pathological basis for both the seizures and comorbid condition. While recognition of the comorbid conditions of pediatric epilepsies is increasing, there has been a lag in the development of effective therapies partly out of concern that drugs used to treat the comorbid conditions could increase seizure susceptibility. There is now some evidence that most drugs used for comorbid conditions are safe and do not lower seizure threshold. Unfortunately, the evidence showing drugs are effective in treating many of the childhood comorbidities of epilepsy is quite limited. There is a great need for randomized, placebo-controlled drug trials for efficacy and safety in the treatment of comorbidities of childhood epilepsy.


Aberrant expression of the pluripotency marker SOX-2 in endometriosis.
Expression of the pluripotency factors SOX-2, OCT-4, KLF-4, and NANOG was analyzed by quantitative real-time polymerase chain reaction, immunohistochemistry, and immunofluorescence microscopy in the endometrium, myometrium, and endometriotic tissue of 36 patients. Aberrant expression of SOX-2 may indicate a stem cell origin of endometriosis, whereas the presence of all progenitor markers in endometrial tissue marks the endometrium as a potential source for induced pluripotent stem cell generation.


Med23 serves as a gatekeeper of the myeloid potential of hematopoietic stem cells.
In response to myeloablative stresses, HSCs are rapidly activated to replenish myeloid progenitors, while maintaining full potential of self-renewal to ensure life-long hematopoiesis. However, the key factors that orchestrate HSC activities during physiological stresses remain largely unknown. Here we report that Med23 controls the myeloid potential of activated HSCs. Ablation of Med23 in hematopoietic system leads to lymphocytopenia. Med23-deficient HSCs undergo myeloid-biased differentiation and lose the self-renewal capacity. Interestingly, Med23-deficient HSCs are much easier to be activated in response to physiological stresses. Mechanistically, Med23 plays essential roles in maintaining stemness genes expression and suppressing myeloid lineage genes expression. Med23 is downregulated in HSCs and Med23 deletion results in better survival under myeloablative stress. Altogether, our findings identify Med23 as a gatekeeper of myeloid potential of HSCs, thus providing unique insights into the relationship among Med23-mediated transcriptional regulations, the myeloid potential of HSCs and HSC activation upon stresses.


Role of maintenance sucralfate in prevention of duodenal ulcer recurrence.
Fifty-nine patients who had duodenal ulcers that were healed following sucralfate administration in a dose of 1 g four times a day were randomly entered into a double-blind, placebo-controlled, 12-month maintenance study to determine whether sucralfate 1 g twice daily prevents recurrence of duodenal ulceration. Patients were assessed endoscopically at four, eight, and 12 months after healing or earlier if clinical relapse occurred. Of the original 59 patients, 53 showed healing with six weeks of therapy, and the remaining six patients required 10 weeks of treatment. Nine patients were subsequently lost to follow-up because of non-compliance, leaving 50 patients for the analysis, 24 who received sucralfate and 26 who received placebo. There were 10 ulcer recurrences in the sucralfate group and the ulcers in 14 (58 percent) patients remaining healed at the end of 12 months. In contrast, there were 21 recurrences in the placebo group with the ulcers in five patients (19 percent) remaining healed at 12 months. Patients who received placebo experienced recurrence more quickly than those who received sucralfate and there was no difference between the two groups in terms of symptomatic and asymptomatic recurrence. There was no alteration in serum aluminium and phosphate levels throughout the study. Smoking seemed to have no adverse effect on recurrence once initial healing had been achieved. Sucralfate is, therefore, an effective and safe maintenance treatment for duodenal ulcer disease.


Colostral transfer of bovine immunoglobulin E and dynamics of serum IgE in calves.
The role of IgE in protective immunity is becoming understood, therefore the colostral transfer of IgE and the age-dependent changes of IgE levels may be important for neonatal immunity. To investigate this question, serum samples were collected from range-fed Hereford cows and their calves from birth through 9 months of age. The sera were assayed for total IgE during the first week postpartum, indicating colostral transfer of IgE. Thereafter, serum levels declined rapidly within 3 weeks from birth. The IgE levels began to increase after 12 weeks of age, and in some cases reached adult levels. The passive transfer of maternal IgE through colostrum may be important in providing early protection from disease, especially against intestinal parasites.


Imaging data analysis using non-negative matrix factorization.
The rapid progress of imaging devices such as two-photon microscopes has made it possible to measure the activity of thousands to tens of thousands of cells at single-cell resolution in a wide field of view (FOV) data. However, it is not possible to manually identify thousands of cells in such wide FOV data. Several research groups have developed machine learning methods for automatically detecting cells from wide FOV data. Many of the recently proposed methods using dynamic activity information rather than static morphological information are based on non-negative matrix factorization (NMF). In this review, we outline cell-detection methods related to NMF. For the purpose of raising issues on NMF cell detection, we introduce our current development of a non-NMF method that is capable of detecting about 17,000 cells in ultra-wide FOV data.


Selective phosphodiesterase 5 inhibition does not reduce propofol sedation requirements but affects speed of recovery and plasma cyclic guanosine 3',5'-monophosphate concentrations in healthy volunteers.
Cyclic guanosine 3',5'-monophosphate (cyclic GMP) has been implicated in modulating the effects of anesthesia. We hypothesized that limiting the breakdown of cyclic GMP through selective phosphodiesterase inhibition would influence propofol sedation requirements and plasma cyclic GMP concentrations. Ten volunteers received 100 mg of sildenafil or placebo orally in this placebo-controlled, double-blind, randomized crossover pilot study. Propofol sedation was achieved using a target-controlled infusion system until loss of verbal contact (LVC). Plasma cyclic GMP concentrations were determined at baseline, LVC, and 30 min after LVC. There was no difference in the amount of propofol used, predicted plasma concentration, or duration of sedation in volunteers after sildenafil compared with placebo treatment. Return of spontaneous verbal contact was faster after sildenafil (4 [3-8] min versus 6 [3-5] min, median [range], P = 0.019). Cyclic GMP concentrations were reduced during propofol sedation in the placebo group compared with baseline (P < 0.004). The plasma cyclic GMP concentrations were larger (P = 0.004) at LVC in the sildenafil group compared with placebo. We have shown that selective phosphodiesterase 5 inhibition decreases recovery time from propofol sedation without affecting propofol requirements. The decrease of plasma cyclic GMP concentrations during propofol sedation in the placebo group indicates a potential role of cyclic GMP in propofol anesthesia in humans. Plasma cyclic guanosine 3',5'-monophosphate (cyclic GMP) concentrations are reduced during propofol sedation. Selective phosphodiesterase 5 inhibition, however, does not reduce propofol sedation requirements or plasma cyclic GMP concentrations but affects speed of recovery in healthy volunteers.


Quantitation of lidocaine and its deethylated metabolites in plasma and urine by gas chromatography-mass fragmentography.
A sensitive, precise and accurate method for simultaneous quantitation of lidocaine and its deethylated metabolites by gas chromatography-mass fragmentography has been developed. Propyl derivatives of the deethylated metabolites are formed directly in either plasma or urine by treatment with propionaldehyde and sodium cyanoborohydride. The propyl derivatives and unchanged lidocaine are extracted, separated by gas chromatography and quantitated by mass fragmentography using mepivacaine as the internal standard. Quantitation of these compounds to levels as low as 50 ng/ml body fluid has been achieved with coefficients of variation less than 10%.


Mesenchymal stem cells: progress toward promise.
Despite having access to embryonic stem cells, many laboratories choose to study adult stem cells, not because of philosophical reasons but because of the practical aspects and day-to-day progress necessary for developing cellular therapeutics. There is certainly the ethical desire and responsibility to provide patients with therapies where few options exist. Multipotential cells have been isolated from adult tissues in many laboratories, characterized and their multipotentiality examined. Mesenchymal stem cells (MSC) can be isolated from several tissues but easily accessible BM seems to be the most common source. These adult stem cells may not be as 'powerful' or diverse as embryonic stem cells may one day become, but at present they offer many advantages for developing cellular therapeutics: ease of isolation, expansion potential, stable phenotype, shippability, and compatibility with different delivery methods and formulations. Their potential use as cellular therapeutics has prompted the investigation of interactions of allogeneic MSC with the immune response. The great importance of cardiovascular medicine has demanded that MSC also be tested in this discipline. We believe MSC continue to provide a substantial scientific and therapeutic opportunity, and have reviewed some of the recent developments in the field.


Serum immunoglobulin levels in cancer patients IV. The influence of therapy on the levels of IgG, IgA and IgM.
The levels of immunoglobulins (IgG, IgA, IgM) were measured in the blood serum of 232 patients with malignant diseases subjected to therapy with irradiation, cytostatic drugs, hormones and active immunotherapy. The values of two samples were compared before and after therapy. The local irradiation with usual doses and technique did not significantly influence the Ig levels. On the contrary, the levels of all three Ig classes decreased after chemotherapy, but only the IgG decrease was significant. A rise of Ig followed active immunotherapy and hormonal therapy but these changes were not significant.


Validation of the ISAAC video questionnaire (AVQ3.0) in adolescents from a mixed ethnic background.
The International Study of Asthma and Allergies in Childhood (ISAAC) has developed an international version of the asthma video questionnaire (AVQ3.0) to measure asthma prevalence. This questionnaire has not been validated in adolescents from a mixed ethnic background. The aims of this study were to compare the video questionnaire with a written questionnaire in the detection of airway hyperresponsiveness to hypertonic saline in a population of adolescents from a mixed ethnic background, and to establish the repeatability and psychometric properties of the asthma video questionnaire. The study was conducted in four secondary schools in Sydney, an area with a high proportion of people from a non-English speaking background. Four hundred and seventy-five students from schools 1 and 2 completed the video questionnaire and a subgroup of these students (n = 170) completed the written questionnaire and a hypertonic saline inhalation challenge. Reproducibility of the questionnaire was evaluated by administering the questionnaire to a subsample of students 2 weeks later. The psychometric properties of the video questionnaire were examined in 852 students at two other schools (schools 3 and 4). One hundred and sixty-nine students aged 13.5 (sd 1.3) years completed both written and video questionnaires, and the hypertonic saline challenge. The students had widely different cultural backgrounds including Asian, South Pacific, Middle Eastern, European and African countries. There was good agreement between the questionnaires for wheeze (kappa 0.42). Questions on the video questionnaire concerning wheezing had good sensitivity (90%) and specificity (68%) for airway hyperresponsiveness to hypertonic saline. The video questionnaire was reproducible (kappa 0.82), had good internal consistency (Cronbach's alpha 0.81) and each question pertained to a single construct explaining 58% of the variance in total score. This study has validated the international version of the ISAAC video questionnaire against airway hyperresponsiveness to hypertonic saline in adolescents from a mixed ethnic background, and identified that the questionnaire has good psychometric properties. The ISAAC video has proved to be a valuable tool for the assessment of asthma prevalence in populations of ethnic diversity.


Translation and validation of the Arabic version of the quality of oncology nursing care scale (QONCS): Psychometric testing in three Arabic countries.
In the Arab world, little is known about cancer patient's satisfaction with the care provided by the oncology nurses. The only explanation for this dearth of knowledge is lack of a specified, valid and reliable tool that can be utilized with all types of cancer. This regional study was conducted to translate and validate the Arabic version of quality of oncology nursing care scale (QONCS). Brislin's model of translation was used with a cross-sectional, cross-cultural and psychometric design. A convenience sample of 517 from three countries (Jordan, Oman and Egypt) completed the study's surveys. The results indicated that the total QONCS-Ar was reliable with Cronbach's alpha 0.88 and 0.84, 0.87, 0.83, 0.89 and 0.86 for being supported and confirmed, with the religious and spiritual care, belonging, being valued and being respected domains respectively. Exploratory factor analysis supported the dimensional structure of the 34-item scale with five domains with Kaiser-Meyer-Oklin (KMO) measuring 0.872 and Bartlett's Test of Sphericity being significant (significant p<0.001) CONCLUSION: QONCS-Ar is a relatively short, valid, reliable and easy to use instrument that can be applied with all types of cancer, research and educational institutions in the Arabic region.


Oribatid mites in different Mediterranean crop rotations fertilized with animal droppings.
Unsustainable soil management is one of the drivers of soil degradation, but impact assessment requires the development of indicators. Oribatids might be considered as early indicators of disturbances due to the stability of their community. The aim of this study was to investigate the feasibility of oribatids as bioindicators of sustainable agricultural practices. Under a dry Mediterranean climate, three fertilization experiments - two under a two-crop rotation system and one under maize monoculture and established 12 years earlier - were sampled 3× for oribatid identification during the last annual cropping cycle. The hypothesis was that different nutrient and crop managements affect the number of oribatid species and individuals present, and these parameters could be used as indicators of soil degradation. In total, 18 oribatid species were identified, and 1974 adult individuals were recovered. Maximum abundance was found prior to sowing. Pig slurry (PS) vs. control, and dairy cattle manure (CM) vs. mineral fertilization increased oribatid abundance. This increase was evident when the average applied rates with PS were ca. 2 Mg of organic matter (OM) ha- 1 yr- 1, or higher than ca. 4 Mg OM ha- 1 yr- 1 for CM. When the preceding crop was wheat and PS or CM were used, Oribatula (Zygoribatula) excavata (which reproduces sexually) predominated. In maize monoculture fertilized with CM, Tectocepheus sarekensis and Acrotritia ardua americana (which can reproduce through parthenogenesis) prevailed vs. Oribatula, which indicated a heavily disturbed soil. Under this specific Mediterranean environment, the predominance of certain parthenogenic oribatid species and the number of individuals provide advanced warning on soil degradation.


The Role of Intrinsic Motivation in the Pursuit of Health Science-Related Careers among Youth from Underrepresented Low Socioeconomic Populations.
A more diverse health science-related workforce including more underrepresented race/ethnic minorities, especially from low socioeconomic backgrounds, is needed to address health disparities in the USA. To increase such diversity, programs must facilitate youth interest in pursuing a health science-related career (HSRC). Minority youth from low socioeconomic families may focus on the secondary gains of careers, such as high income and status, given their low socioeconomic backgrounds. On the other hand, self-determination theory suggests that it is the intrinsic characteristics of careers which are most likely to sustain pursuit of an HSRC and lead to job satisfaction. Intrinsic and extrinsic motivation for pursuing an HSRC (defined in this study as health professional, health scientist, and medical doctor) was examined in a cohort of youth from the 10th to 12th grade from 2011 to 2013. The sample was from low-income area high schools, had a B- or above grade point average at baseline, and was predominantly: African American (65.7 %) or Hispanic (22.9 %), female (70.1 %), and children of foreign-born parents (64.7 %). In longitudinal general estimating equations, intrinsic motivation (but not extrinsic motivation) consistently predicted intention to pursue an HSRC. This finding provides guidance as to which youth and which qualities of HSRCs might deserve particular attention in efforts to increase diversity in the health science-related workforce.


The maxillary step osteotomy and Steinmann pin stabilization.
Use of the maxillary step osteotomy facilitates the transfer of information obtained by prediction tracing and model surgery to the patient at the time of surgery and allows for a well-visualized bone grafting area in cases of maxillary advancement. The use of Steinmann pin maxillary stabilization provides improved anteroposterior and vertical stabilization in indicated cases.


Is complete resection of hypertrophic adenoma of the prostate possible with TURP?
Whether complete resection was possible with TURP was explained. A lot of adenoma remains after transurethral resection of the prostate (TURP), the other hand transurethral enucleation of the prostate (TUE) is useful for complete resection of an adenoma.


Association of serum potassium with decline in residual kidney function in incident hemodialysis patients.
Hyperkalemia is associated with kidney function decline in patients with non-dialysis dependent chronic kidney disease, but this relationship is unclear for residual kidney function (RKF) among hemodialysis (HD) patients. We conducted a retrospective cohort study of 6655 patients, who started HD January 2007 and December 2011 and who had data on renal urea clearance (KRU). Serum potassium levels were stratified into four groups (i.e. ≤4.0, >4.0 to ≤4.5, >4.5 to ≤5.0 and >5.0 mEq/L) and 1-year KRU slope for each group was estimated by a linear mixed-effects model. Higher serum potassium was associated with a greater decline in KRU, and the greatest decrease in KRU (-0.20, 95% confidence interval -0.50 to -0.06) was observed for baseline potassium >5.0 mEq/L in the fully adjusted model. Mediation analysis showed that KRU slope mediated 1.78% of the association between serum potassium and mortality. Hyperkalemia is associated with a decline in RKF amongst incident HD patients. These findings may have important clinical implications in the management of hyperkalemia in advanced CKD if confirmed in additional clinical trials.


Genetic mapping of antigenic determinants on a membrane protein.
The antigenic determinants recognized by two monoclonal antibodies were mapped on LamB, an outer membrane protein of Escherichia coli. The procedure consisted of performing immunoprecipitation experiments with extracts of strains which produced truncated fragments of LamB, either in a free form (deletion and nonsense mutants) or fused to another polypeptide (malK-lamB and lamB-lacZ fusion strains). The conclusion is that the two antigenic determinants are located within 70 residues from the COOH-terminal end of LamB, which contains a total of 421 amino acids. Since these two antigenic sites were previously demonstrated to be exposed at the cell surface, it follows that a COOH-terminal portion of LamB must be located on the outer surface of the outer membrane.


Many faces of Meckel's diverticulum and its complications.
Meckel's diverticulum is the most common congenital abnormality of the gastrointestinal tract. It is a true diverticulum containing all layers of the intestinal wall and identified as a saccular, blind-ending structure located on the antimesenteric border of the distal ileum. Most patients remain asymptomatic during their lifetime. Symptomatic cases are nonspecific and can present as small-bowel obstruction, diverticulitis, perforation, gastrointestinal bleeding, and rarely, a neoplasm. Therefore, the radiological diagnosis is of paramount important for proper patient management.


The effect of inhaled bronchoconstrictors on transcutaneous gas tensions in normal adult subjects.
The administration of histamine and leukotriene D4 (LTD4) by nebulised aerosol in logarithmically increasing doses to normal subjects resulted in significant bronchoconstriction. Transcutaneous oxygen tension (tcPO2) was monitored during and after the bronchial challenge tests. Following histamine challenge there was significant hypoxaemia in all subjects (mean fall in tcPO2, 20 mmHg). However, following LTD4 administration, there was a small and insignificant fall in tcPO2. Transcutaneous carbon dioxide tension (tcPCO2) was also monitored throughout bronchial challenge, but showed no significant change. We suggest that the hypoxaemia following histamine challenge was due to increased ventilation/perfusion (V/Q) mismatching in the lung induced by histamine deposition.


Structure and impact of root-associated fungi in treatment wetland mesocosms.
Root fungal endophytes have been shown to play a positive role in soil phytoremediation by immobilizing or degrading contaminants. In comparison, little is known about their ecological functions and possible role in improving plant performance in treatment wetlands. In a greenhouse study, we compared the structure of fungal communities associated with Phragmites australis roots in treatment wetland mesocosms fed with pre-treated wastewater to mesocosms fed with drinking water. We evaluated the role of water source as an environmental filter structuring fungal communities, and correlated the relative abundances of fungal taxa with key services delivered by the wetlands (i.e., biomass production and nutrient removal). Mesocosms fed with wastewater had higher fungal alpha-diversity. Contrary to expectations, many fungi were unique to drinking water-fed mesocosms, suggesting that the oligotrophic conditions prevailing in these mesocosms benefited specific fungal taxa. On the other hand, wastewater-fed mesocosms had a slightly higher proportion of sequence reads belonging to fungal species recognized as potential endophytes and phytopathogens, highlighting the potential role of wastewater as a source of plant-associated fungi. Interestingly, we found contrasted association patterns between fungal species' relative abundances and different treatment wetland services (e.g., N vs P removal), such that some fungi were positively associated with N removal but negatively associated with P removal. This suggests that fungal endophytes may be functionally complementary in their contribution to distinct mesocosm services, thus supporting arguments in favor of microbial diversity in phytotechnologies. Because of the wide alpha-diversity of fungal communities, and the fact that with current databases, most species remained unassigned to a specific function (or even guild), further investigation is needed to link fungal community structure and service delivery in treatment wetlands.


Neuroprotective Effects of Lycium Barbarum Fruit Extract on Pink1B9Drosophila Melanogaster Genetic Model of Parkinson's Disease.
Lycium barbarum (LB) is a famous traditional Chinese medicinal plant as well as food supplement possessing various pharmacological functions such as anti-aging and antioxidant effects. The Parkinson's disease (PD)-related kinase Pink1 plays vital role in maintaining the neuron cell homeostasis, having been recognized as a potential target for the development of anti-PD drugs. In this work, the neuroprotective effects of methanol extract of LB fruit (LBFE) were investigated using a Drosophila PD model (PINK1B9) and a human neuroblastoma SH-SY5Y cell line. We found that when LBFE was supplied to the PINK1B9 flies at 6, 12, and 18 days of age, it raised the ATP and dopamine levels at all ages, extended life span, improved motor behavior, and rescued olfactory deficits of the PINK1B9 flies. In addition, histopathological examinations indicated that muscle atrophy in thoraces of the mutant flies was significantly repaired. Finally, LBFE was able to rescue the SH-SY5Y cells against MPP+-induced neurotoxicity. This work reports for the first time the anti-PD potential of L. barbarum fruit extract in PINK1 mutant fruit flies, presenting a new viewpoint for studing the mechanism of action of LBFE.


Osteoporosis and atherosclerosis: a post-mortem MDCT study of an elderly cohort.
To evaluate how far fracture status and bone mineral density (BMD) correlate with the vascular calcification score (CS). On 29 complete human cadavers (17 female, 12 male; mean age at death was 85.57 years), multi-detector computed tomography was performed to assess the spine fracture status (fracture vs non-fracture [FX vs non-FX]) and CS of the coronary arteries (Coro-CS), the aorta (Aorta-CS) and the pelvic vessels (Iliac-CS). Quantitative computed tomography of the lumbar spine was performed to estimate overall BMD (osteoporotic [BMD <80 mg/cm(3)] vs non-osteoporotic [BMD ≥ 80 mg/cm(3)]). Gender-specific differences in statistical significance were only observed for Aorta-CS and Iliac-CS but not for Coro-CS. When comparing the osteoporotic with the non-osteoporotic group, statistically significant differences were only found for Iliac-CS (P < 0.05); however, linear regression analysis showed none of the CSs to significantly correlate with BMD. In our small post-mortem elderly population, statistically significant associations of fracture status and BMD with CS were only observed between the osteoporotic and non-osteoporotic groups for the pelvic vessels but not for the coronary arteries and the aorta. • Gender-specific differences were observed for aortic and iliac calcification score (CS). • There was no difference in coronary CS between females and males. • Only iliac CS was different in osteoporotic and non-osteoporotic subjects. • In linear regression analysis, CS showed no correlation with BMD. • In univariate analysis, gender was a BMD and iliac CS confounder.


[Comparison of different DON-standards].
DON is the only mycotoxin of the trichothecene group that has been regulated in food so far by the German authorities. The quantitative determination of DON in food and feed therefore is of great importance regarding compliance with legal limits. An important source of measurement error is the bias introduced by different absolute concentration of calibration standards. To make an estimation of the contribution of calibration standards to total error six different DON-standards provided by the participants of the project "Analysis and occurence of important Fusarium toxins (DON and ZEA) and uptake of these toxins by the German consumer" sponsored by the German Ministry of Consumer Protection, Nutrition and Agriculture (BMVEL, Projekt BLE 00HS055) were analyzed and compared to three batches of commercial standard solutions. The range of the results was between 29.2 and 26.3% for the laboratory standards and 11.3 respective 3% for the commercial standards depending on different calculation modes (UV height and area and fluorescence height). Therefore a substantial reduction of the measurement error by using commercial standards instead of laboratory-prepared standards seems possible.


Biosynthesis, cDNA and amino acid sequences of a precursor of conglutin delta, a sulphur-rich protein from Lupinus angustifolius.
The biosynthesis of conglutin delta has been studied in developing cotyledons of Lupinus angustifolius L. Precursors of conglutin delta formed the major sink for [35S]-cysteine incorporated by developing lupin cotyledons, and these precursors were rapidly sequestered into the endoplasmic reticulum. The sequence of a cDNA clone coding for one such precursor of conglutin delta was determined. The structure of the precursor polypeptide for conglutin delta predicted from the cDNA sequence contained an N-terminal leader peptide of 22 amino acids directly preceding a subunit polypeptide of Mr 4520, together with a linking region of 13 amino acids and a subunit polypeptide of Mr 9558 at the C-terminus. The amino acid sequence predicted from the cDNA sequence showed minor variations from that established by sequencing of the protein purified from mature dried seeds (Lilley and Inglis, 1986). These were consistent with the existence of a multi-gene family coding for conglutin delta. Comparison of the sequences of conglutin delta with those of other 2S storage proteins showed that the cysteines involved in internal disulphide bridges between the mature subunits of conglutin delta, were maintained throughout this family of proteins but that little else was conserved either at the protein or DNA level.


Differential regulation of urokinase-type-1 inhibitor complex endocytosis by phorbol esters in different cell lines is associated with differential regulation of alpha 2-macroglobulin receptor and urokinase receptor expression.
Complex between urokinase and its type-1 inhibitor (uPA-PAI-1) may, when bound to the urokinase receptor (uPAR), be endocytosed by an ensuing binding of the complex to the multiligand receptors alpha (2)-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR/LRP) and glycoprotein 330 (gp330). We have found that phorbol esters regulate endocytosis of uPA-PAI-1 differently in different cell lines. In COS-1 cells, expressing uPAR and high levels of alpha 2MR/LRP under basal conditions, phorbol esters cause a time-dependent decrease in endocytosis concomitantly with a parallel down-regulation of alpha 2MR/LRP expression. An up-regulation of uPAR expression was also observed. General endocytosis via the clathrin-coated pit pathway was not affected by PMA treatment, as judged from measurements of transferrin endocytosis. In LLC-PK1 cells, expressing alpha 2MR/LRP but not uPAR under basal conditions, phorbol esters transiently increase endocytosis in parallel with a transient induction of uPAR expression, while there was virtually no change in alpha 2MR/LRP expression. Differential regulation of endocytosis therefore seems to be caused by differential regulation of the receptors, with either the alpha 2MR/LRP-level (in COS)-1 cells) or the uPAR-level (in LLC-PK1 cells) being rate-limiting.


Semi-empirical models for remote estimating colored dissolved organic matter (CDOM) in a productive tropical estuary.
Inland waters are important components of the global carbon cycle as they regulate the flow of terrestrial carbon to the oceans. In this context, remote monitoring of Colored Dissolved Organic Matter (CDOM) allows for analyzing the carbon content in aquatic systems. In this study, we develop semi-empirical models for remote estimation of the CDOM absorption coefficient at 400 nm (aCDOM) in a tropical estuarine-lagunar productive system using spectral reflectance data. Two-band ratio models usually work well for this task, but studies have added more bands to the models to reduce interfering signals, so in addition to the two-band ratio models, we tested three- and four-band ratios. We used a genetic algorithm (GA) to search for the best combination of bands, and found that adding more bands did not provide performance gains, showing that the proper choice of bands is more important. NIR-Green models outperformed Red-Blue models. A two-band NIR-Green model showed the best results (R2 = 0.82, RMSE = 0.22 m-1, and MAPE = 5.85%) using field hyperspectral data. Furthermore, we evaluated the potential application for Sentinel-2 bands, especially using the B5/B3, Log(B5/B3) and Log(B6/B2) band ratios. However, it is still necessary to further explore the influence of atmospheric correction (AC) to estimate the aCDOM using satellite data.


Radiometric studies on the oxidation of [1-14C]fatty acids and [U-14C]L-amino acids by mycobacteria.
A radiometric assay system has been used to study oxidation patterns of [1-14C]fatty acids and [U-14C]L-amino acids by drug-susceptible and drug-resistant organisms of the genus Mycobacterium. Two strains of M. tuberculosis susceptible to all drugs, H37Rv TMC 102 and Erdman, were used. Drug-resistant organisms included in this investigation were M. tuberculosis H37Rv TMC 303, M. bovis, M. avium, M. intracellulare, M. kansasii and M. chelonei. The organisms were inoculated into a sterile system containing liquid 7H9 medium along with one of the [1-14C]fatty acids or [U-14C]L-amino acids. Although each individual organism displayed a different pattern of fatty acid oxidation, these patterns were not distinctive enough for identification of the organism. Susceptible and resistant mycobacteria did not display any preferential oxidation of long chain or of short chain fatty acids that might help to distinguish these organisms. As with the fatty acid series, differential oxidation patterns for amino acids could be recognized, but again these patterns were not distinctive enough to identify each organism. Complex amino acids such as proline, phenylalanine and tyrosine were of no use in identification of mycobacteria, since virtually all organisms failed to oxidize them. Identification of each individual organism was feasible using a combination of fatty acids and amino acids which included butyric, octanoic, oleic, glycine and alanine. There was no combination of substrates able to separate susceptible and resistant organisms.


Draft Genome Sequences of Biofilm-Forming and Non-Biofilm-Forming Nontyphoidal Salmonella enterica Serovars.
The genetic basis for biofilm formation among nontyphoidal salmonellae (NTS) remains poorly understood. This draft genome submission provides initial insights on the genetic differences between biofilm-forming and non-biofilm-forming clinical and environmental NTS serovars.


Bladder outflow obstruction--a cause of denervation supersensitivity.
Eighteen Landrace pigs and 12 Göttingen mini-pigs were evaluated in a study of experimental bladder outflow obstruction. Twenty-two of the animals underwent partial bladder outflow obstruction for periods up to 12 months. The subsequent changes were assessed using cystometric, physiological and morphological means. There was a consistent increase in the voiding pressures and a concomitant reduction in the flow rates in all the obstructed animals. Seventy-seven per cent of the obstructed animals showed cystometric evidence of bladder instability. In vitro studies showed an increase in sensitivity to exogenously applied agonists and a reduction in sensitivity to intramural nerve stimulation. Morphological studies showed an inverse correlation between neuronal density and the duration of obstruction. These changes are typical of post-junctional supersensitivity secondary to partial denervation. These results suggest that agents capable of stabilising the bladder smooth muscle membrane may be useful in the treatment of detrusor instability secondary to bladder outflow obstruction.


Analysis of an institutional protocol for thyroid lobectomy: Utility of routine intraoperative frozen section and expedited (overnight) pathology.
Intraoperative frozen section (FS) often is performed in patients who undergo thyroid lobectomy to determine the need for completion thyroidectomy. At our institution, if FS pathology is benign, final pathology is expedited overnight. The aim of this study was to determine the utility of FS and to identify a cost-effective management algorithm for thyroid lobectomy. A retrospective review was performed of patients who underwent thyroid lobectomy between January 2009 and May 2013. Preoperative cytology ranged from "benign" to "suspicious for malignancy." Clinically significant cancers were defined as >1 cm in size, or multifocal microcarcinomas. Of the 192 patients who underwent thyroid lobectomy with FS, FS was suspicious for malignancy in 5 (3%) patients; 1 (0.5%) underwent immediate completion thyroidectomy. On final pathology, 9 (5%) patients had clinically significant cancers and underwent completion thyroidectomy. FS had a sensitivity and positive predictive value of 22% and 40%, respectively, in identifying clinically significant thyroid cancer. Cost of thyroid lobectomy at varying rates of same-day discharge favored thyroid lobectomy without FS but with expedited pathology for all scenarios. At our institution, there appears to be limited utility of FS at the time of thyroid lobectomy given the low predictive value for diagnosing a clinically significant thyroid cancer. In patients who are admitted overnight, expedited pathology is slightly less costly and may improve patient quality-of-life and decrease costs by avoiding delayed completion thyroidectomy. Overnight pathology for patients who undergo thyroid lobectomy may achieve modest cost-savings depending on institutional FS results and rates of malignancy.


An allosteric ribozyme generator and an inverse folding ribozyme generator: Two computer programs for automated computational design of oligonucleotide-sensing allosteric hammerhead ribozymes with YES Boolean logic function based on experimentally validated algorithms.
Designing oligonucleotide-sensing ribozymes using computational approaches is advantageous to in vitro selection methods for efficiency and accuracy. Allosteric ribozymes can be computationally designed for various applications in gene therapy, designer gene control systems, biosensors, and molecular computation. Here we present two programs, the allosteric Ribozyme Generator (RG) and the Inverse Folding Ribozyme Generator (IFRG), engineered to generate allosteric ribozymes with YES logic. The RG computes allosteric ribozyme sequences' secondary structure using the minimal sequence of the hammerhead ribozyme by inserting oligonucleotide binding site (OBS) elements in the second stem. The IFRG program uses inverse folding to generate allosteric ribozyme sequences with OBS bearing distinct sequences and similar folding. For the generation of the OBS sequences, random search algorithms are employed. Allosteric ribozyme sequences generated by the RG can be used as a matrix for the IFRG program. This approach applies RNA-folding algorithms based on applying thermodynamic parameters using the partition function of the RNAfold, and the RNAinverse source codes from the Vienna RNA folding package. The two algorithms apply dynamic programming and random search algorithms to generate in silico allosteric ribozymes with predefined properties within minutes using a personal computer with over 90% accuracy, without high computation power as experimentally validated and published by us previously.


An efficient catalytic method for hydrophosphination of heterocumulenes with diethylzinc as precatalyst without a solvent.
Commercially available compound ZnEt2 acts as an efficient precatalyst for the solvent-free hydrophosphinations of heterocumulenes using Ph2PH as reagent. As far as we knew, this has been not reported in group 12 metal catalyzing reactions. A suggested mechanism of this reaction is explored, and the intermediate [{Ph2PC(NiPr)2}ZnEt]2 is obtained and characterized by a single-crystal X-ray structural analysis.


ESC/EAS guidelines for the detection, prevention, and treatment of individuals at risk of a first myocardial infarction: effect of 5 years of updates and the new SCORE2.
The European Society of Cardiology (ESC) has released three consecutive guidelines within 5 years addressing cardiovascular prevention, risk scores, and cholesterol treatment. This study aims to evaluate whether the 2021 ESC guidelines improved the eligibility of individuals for primary prevention statin therapy before their first ST-segment elevation myocardial infarction (STEMI), and for intensive lipid-lowering treatments in secondary prevention. The cardiovascular risk category of 2757 consecutive individuals admitted for a first STEMI was evaluated to assess whether they would have been eligible for primary prevention statins according to 2021 vs. 2019 and 2016 ESC guidelines. Eligibility for intensive lipid-lowering therapy in secondary prevention was assessed according to the real-life follow-up low-density lipoprotein cholesterol (LDL-C) and the expected follow-up LDL-C. More individuals would have been eligible for primary prevention statins according to 2021 and 2019 vs. 2016 guidelines (61.8% vs. 38.7% vs. 23.6%, P < 0.01), a finding observed in both men (62.3% vs. 35.0% vs. 24.9%, P < 0.01) and women (60.2% vs. 50.7% vs. 19.3%, P = 0.18). Only 27% of individuals reached the LDL-C objective of 55 mg/L in secondary prevention: using the ESC stepwise approach, 61.7% were eligible for higher doses of statins, 26.2% for ezetimibe, and 12.1% for a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (PCSK9i). Based on expected LDL-C reductions, eligibility for a PCSK9i in secondary prevention was greater with 2021 vs. 2016 guidelines (44.5% vs. 22.5%, P < 0.01). The 2021 ESC guidelines improved the detection and treatment of individuals at risk for a first myocardial infarction. In secondary prevention, 70% of patients kept LDL-C levels above 55 mg/dL: increasing the statin dose and adding ezetimibe were the most frequently recommended therapeutic actions.


Immunity induced by live attenuated Salmonella vaccines.
Studies on the degree and specificity of protection conferred by immunization with aroA salmonella live vaccines in BALB/c mice are described. Animals were immunized i.v. and challenged orally 3 months later to ensure that the vaccine had been cleared from the tissues. Vaccination with Salmonella typhimurium aroA SL3261 conferred very good protection against virulent S. typhimurium C5 (over 10,000 x LD50). The specificity of cross protection was studied using S. typhimurium, Salmonella enteritidis and Salmonella dublin for vaccination and challenge, including challenge with variants of S. typhimurium and S. enteritidis of similar virulence which differed in the main LPS (lipopolysaccharide) antigen (0-4 or 0-9). S. typhimurium SL3261 gave very good protection against S. typhimurium C5 (0-4), but no protection against S. enteritidis Se795 (0-9). However, challenge with strains differing in the main 0 antigens showed that, although protection was generally better to strains expressing the same LPS type as the vaccine, specificity of protection was determined more by the background (S. typhimurium or S. enteritidis) of the parent strain used for the challenge than by 0 factors 4 or 9, suggesting that other factors could be involved. The nature of the antigen(s) responsible for protection in this model is unclear, but it would not appear to be the main 0-specific antigen. An S. enteritidis Se795 aroA vaccine was far less effective than S. typhimurium SL3261; it conferred good protection against the homologous wild type at 2 weeks post-vaccination, but far less at three months (approx 10-200 x LD50). This was unexpected, as the persistence of the S. enteritidis vaccine in the liver and spleen was similar to that of S. typhimurium SL3261, and the S. enteritidis and S. typhimurium challenge strains were of similar virulence. An S. dublin aroA vaccine conferred similar protection against wild type S. dublin (approx 300 x LD50).


Acute and long-term outcomes of simultaneous atrioventricular node ablation and leadless pacemaker implantation.
Leadless pacemaker (LDP) allows implantation using a femoral approach. This access could be utilized for conventional atrioventricular nodal ablation (AVNA). It could facilitate unifying the two procedural components. Data regarding its feasibility and long-term outcomes remain lacking. We aim to evaluate the feasibility and long-term outcomes of sequential LDP and AVNA. Prospective, observational multicenter study including consecutive patients with indication for single-chamber pacemaker placement. In those with additional indication for AVNA, ablation was performed immediately after the LPD through the same sheath. A total of 137 patients were included. Mean age was 77.9 ± 10.5 years; 74 (54%) were men. Immediately following LDP implantation, 27 patients (19.7%) underwent concurrent AVNA. There were six (5.5%) complications in patients referred for LDP procedures and three (11%) in those who underwent a combined approach. None of these complications were solely attributable to the added AVNA component. No mechanical dislodgement, electrical damage to any device, or electromagnetic interference ever took place. During a mean follow-up period of 123 ± 48 days, three patients (3.6%) died of noncardiovascular causes. The remaining population stayed alive without significant arrhythmias. There were no relevant differences with regard to sensing and pacing thresholds between patients in the two groups. AVNA can safely be performed immediately following LDP. A combined approach obviates the need for additional vascular access and optimizes feasibility and comfort for patients and healthcare providers. It offers an acceptable safety and efficacy profile, both acutely and upon intermediate-term follow-up.


Three-dimensional-printed titanium implants for severe acetabular bone defects in revision hip arthroplasty: short- and mid-term results.
Severe acetabular bone defect is challenging in revision hip arthroplasty. In the present study, we aimed to present new treatment options with the 3D printing technique and analyze the clinical and radiographic outcomes of 3D-printed titanium implants for the treatment of severe acetabular bone defects in revision hip arthroplasty. A total of 35 patients with Paprosky type 3 bone defect and pelvic discontinuity (PD), who underwent hip revisions using 3D-printed titanium implants between 2016 and 2019 at our institution, were retrospectively reviewed. Patient-specific 3D-printed titanium augments and shells (strategy A) were used in 22 type 3A and two type 3B patients. Custom 3D-printed flanged components (strategy B) were used in 11 type 3B patients, including five PD. The clinical outcomes were evaluated with the Harris hip score (HHS). In addition, radiographic results were analyzed by the hip centre of rotation (V-COR and H-COR), implant failure, and survivorship. The mean follow-up was 41.5 months (range, 16-62). The HHS was improved from 47.8 ± 8.2 pre-operatively to 78.1 ± 10.1 at one year follow-up and 86.4 ± 5.1 at the last follow-up (p < 0.01). Post-operative V-COR and H-COR of the operated side were 20.8 ± 2.0 mm and 30.2 ± 1.6 mm compared with 51.4 ± 4.1 mm and 33.9 ± 9.0 mm pre-operatively (p < 0.01). The complications included one dislocation and one partial palsy of the sciatic nerve. At the latest follow-up, no radiological component loosening or screw breakage was present. 3D-printed titanium implants showed satisfactory short- and mid-term clinical and radiographic outcomes. It was an effective therapeutic regimen with a low rate of complications, providing a patient-specific and reliable strategy for the severe acetabular bone defect in revision hip arthroplasty.


Angiographic and pathologic features of probable primary carcinoid-like hepatic tumors.
The angiographic and pathologic features of two cases of primary carcinoid-like hepatic tumors are described. Neither patient had the carcinoid syndrome.


Circulating Non-coding RNAs as Potential Biomarkers for Ischemic Stroke: A Systematic Review.
Recent studies have demonstrated that dysregulated non-coding RNAs (ncRNAs) are involved in the pathogenesis of ischemic stroke (IS), including neuroinflammation, apoptosis, atherosclerosis, and angiogenesis. However, discrepant results make it difficult to apply ncRNAs to clinical practice. Therefore, we performed a meta-analysis to evaluate and elucidate the diagnostic value of ncRNAs in IS. We searched the literature in four databases-PubMed, Web of Science, EMBASE, and the Cochrane Library-up to December 31, 2020, to identify the relationship between differentially expressed ncRNAs and IS. Pooled sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the corresponding 95% confidence intervals (95% CIs) were calculated to assess the diagnostic performance of ncRNAs. Fifteen studies on microRNAs (miRNAs) including 1687 IS patients and eight studies on long non-coding RNAs (lncRNAs) including 741 IS patients were included in our study. Estimates of the identification efficiency of miRNAs from the 15 studies were as follows: 0.76 (95% CI: 0.67-0.84) for sensitivity (SEN), 0.83 (95% CI: 0.77-0.88) for specificity (SPE), 4.5 (95% CI: 3.4-6.1) for PLR, 0.29 (95% CI: 0.20-0.40) for NLR, and 16 (95% CI: 10-26) for DOR. The area under the curve (AUC) of the summary receiver operator characteristic (SROC) curve showed diagnostic accuracy of 0.87 (95% CI: 0.84-0.90); thus the diagnostic value of all the miRNAs was moderate. In addition, the results for lncRNAs were as follows: 0.73 (95% CI: 0.69-0.77) for SEN, 0.75 (95% CI: 0.70-0.79) for SPE, 2.9 (95% CI: 2.4-3.4) for PLR, 0.36 (95% CI: 0.31-0.42) for NLR, 8 (95% CI: 6-11) for DOR, 0.80 (95% CI: 0.76-0.83) for AUC, and a moderate diagnostic value. Our study revealed that blood-circulating ncRNAs could be a moderately effective candidate biomarker for the diagnosis of IS. Furthermore, the combined lncRNAs showed more accurate diagnostic properties than single lncRNAs, and some single miRNAs (e.g., miR-107) showed better diagnostic performance, which may contribute to IS clinical practice.


Treatment of hyperphosphatemia: the dangers of high PTH levels.
The control of secondary hyperparathyroidism (SHPT) in pediatric chronic kidney disease is of utmost importance. Even though parathyroid hormone (PTH) is an important biomarker of mineral and bone disorders associated to CKD (CKD-MBD), calcium, phosphate, alkaline phosphatase, and vitamin D are also crucial and should be assessed together. In pediatric dialysis, high PTH levels have been associated with impaired longitudinal growth, bone disease, cardiovascular comorbidities, left ventricular hypertrophy, anemia, and even mortality (when PTH levels were above 500 pg/mL, i.e., 8.3-fold the upper normal limit (UNL)). As such, high PTH levels are for sure deleterious, but too low PTH levels have also been shown to impair growth and to promote vascular calcifications because of the underlying adynamic bone. This manuscript is part of a pros and cons debate for keeping PTH levels within the normal range in pediatric CKD, focusing on the pros. High bone turnover lesions can occur at lower PTH levels than "current" guidelines would suggest; thus, PTH alone is not a good predictor of the underlying osteodystrophy. PTH results can vary locally depending on the assay. Existing guidelines for PTH targets are conflicting and based on a very little evidence. However, the 120-180 pg/mL (2- to 3-fold the UNL) range is common to most of the guidelines; it seems to be a reasonable target in children undergoing dialysis, even though it does not correspond to "normal" PTH levels. As always, the philosophy of PTH levels in pediatric dialysis may be balanced, i.e., "not too low, not too high, and keep phosphate under control."


Multifaceted roles of interleukin-7 signaling for the development and function of innate lymphoid cells.
Recently, additional innate lymphocyte subsets have been identified that express germline encoded immunoreceptors and respond to cytokine cues. Among these, innate lymphoid cells (ILC) at mucosal surfaces are of significant interest because they were found to play important roles for lymphoid organogenesis, tissue homeostasis and repair, for immunity to various infections but also have been involved as disease-promoting cells in models of chronic inflammatory diseases and of autoimmunity. Their functional and transcriptional programs strikingly resemble that of the various T helper cell subsets suggesting that these programs are already pre-formed in the innate immune system and that these may be more conserved than previously appreciated. Interestingly, all ILC subsets express the interleukin 7 receptor α chain and IL-7 signaling has been involved in various aspects of their developmental and functional programs. Here, we will review the role of IL-7 signaling for the differentiation, maintenance and function of two important ILC subsets, lymphoid tissue inducer cells (i.e., RORγt(+) ILC) and natural helper cells (i.e., type 2 ILC). We will also put emphasis on the recently discovered role of IL-7 in controlling plasticity of RORγt(+) ILC.


New criteria for estimating baroreflex sensitivity using the transfer function method.
Computer simulations were carried out to appraise three new criteria for the estimation of baroreflex sensitivity (BRS) using the transfer function method. The major goal was to identify a computation procedure able to overcome the intrinsic limitations of the classical coherence criterion. Four representative shapes of the gain function and three different average gains (2, 5 and 8 ms(mmHg)(-1) in the low-frequency (LF) band (0.04-0.15Hz) were considered. The signal-to-noise ratio was made to vary so that the peak coherence in the LF band changed from 0.15 to 0.9. All simulation parameters were derived from previous observations in healthy subjects and heart disease patients. The error of the estimated gain function was obtained from its confidence interval. BRS was computed as average gain in the LF band: (a) including in the average only those points having error < or = threshold (criterion 1, C1); (b) calculating the mean error in the band and accepting BRS measurements only when this error was < or = threshold (criterion 2, C2); (c) including in the average all points, regardless of the error (criterion 3, C3). The three criteria were compared in terms of measurability (percentage of measured BRS) and accuracy (bias and SD of BRS). Using C1 and C2, measurability dropped to 10% when the peak coherence in the LF band decreased, respectively, to 0.18-0.41 and to 0.26-0.53, depending on the shape and strength of the gain. In this condition (lower bound of measurability), worst bias and SD (average gain: 8 ms(mmHg)(-1)) were, respectively, 0.8 ms(mmHg)(-1) and 3.3ms(mmHg)(-1) (C1), and 0.1 ms(mmHg)(-1) and 1.0 ms(mmHg)(-1) (C2). C3, by definition, always ensured 100% measurability and showed bias and SD comparable with, or even lower than, C1 and C2, within the common range of measurable BRS. In the extreme condition of 0.15 coherence, bias and SD were, respectively, 1.7 ms(mmHg)(-1) and 2.3ms(mmHg)(-1) (average gain: 8ms(mmHg)(-1)). Hence, error checking (C1 and C2) dramatically reduced measurability and did not improve accuracy of BRS measurements compared with performing no error check (C3). In conditions of low signal-to-noise ratio and/or impaired baroreflex gain, leading to markedly reduced coherence, the simple average of the gain function in the LF band allows BRS to be estimated with accuracy adequate for clinical purposes.


Postpartum Maternal Tethering: A Bioethics of Early Motherhood.
This article proposes a new way of conceptualizing the ethical relationship between postpartum mothers and their newborn babies. I suggest that the intertwinement of mother and baby - and the tensions that this intertwinement produces - do not disappear with birth, but rather persist throughout the postpartum period in the form of postpartum maternal tethering. I draw upon three years of ethnographic fieldwork and training in the US and China to argue that the dependency associated with postpartum maternal tethering makes it extremely difficult for postpartum mothers to act autonomously, even in the relational sense. I then examine how breaches in the postpartum maternal tether can open up new possibilities for thinking about the bioethics of vulnerability, dependency and care, by denaturalizing and de-sanctifying the mother-baby relationship and diversifying newborn care.


Transcription initiation sites of the leucine operons of Salmonella typhimurium and Escherichia coli.
Evidence for a transcription attenuation site downstream from the leu promoter was obtained by transcription experiments in vitro. Most transcription initiated in vitro from leuP is terminated prematurely, resulting in the synthesis of a 160 nucleotide leader RNA. We define here the point at which transcription is initiated in vitro and in vivo and demonstrate that the site of premature termination is between the promoter and the first structural gene (leuA). Additional nucleotide sequences are presented that extend the known sequence 200 base-pairs upstream and 300 base-pairs downstream from leuP. The location of the promoter-proximal end of cistron leuA was deduced by comparing nucleotide sequence data with the sequence of the ten amino acids at the N-terminus of alpha-isopropylmalate synthase. To facilitate the isolation of quantities of material for sequencing experiments, the enzyme was isolated from a plasmid-containing strain, CV605, grown under conditions of leucine limitation. Under such conditions, about 20% of the total soluble protein of strain CV605 is alpha-isopropylmalate synthase and another 20% is beta-isopropylmalate dehydrogenase (leuB product).


Impact of metabolic syndrome and metabolic dysfunction-associated fatty liver disease on cardiovascular risk by the presence or absence of type 2 diabetes and according to sex.
To determine the impact of metabolic syndrome (MetS) and/or metabolic dysfunction-associated fatty liver disease (MAFLD), which are pathophysiologically similar and include insulin resistance, on the development of new-onset cardiovascular disease with and without type 2 diabetes and according to sex. This study included 570,426 individuals without a history of cardiovascular disease who were enrolled in a nationwide claims database from 2008 to 2016 and were classified by the presence or absence of MetS and/or MAFLD stratified by the presence or absence of type 2 diabetes and sex. The fatty liver index was used to determine the presence or absence of fatty liver that required a diagnosis of MAFLD. Risks of developing coronary artery disease (CAD) and cerebrovascular disease (CVD) in each category were analyzed using a multivariate Cox proportional hazard model. During a median follow-up of 5.2 years, 2252 CAD and 3128 CVD events occurred. Without type 2 diabetes the hazard ratio (HR) (95% CI) for CAD/CVD compared with neither MAFLD nor MetS was 1.32 (1.17-1.50)/1.41(1.28-1.57) for MAFLD only (without MetS), 1.78 (1.22-2.58)/1.66 (1.34-2.06) for MetS only (without MAFLD), and 2.10 (1.84-2.39)/1.73 (1.54-1.95) for MAFLD + MetS. For those with type 2 diabetes, the HR for CAD for MAFLD only (compared with neither MAFLD nor MetS) was 1.29 (1.06-1.58), for MetS only 1.34 (0.84-2.13), and for MAFLD + MetS 1.22 (1.02-1.47). For CVD, there was a significant increase in HR only in MAFLD + MetS [1.44 (1.18-1.76)]. The results of the analysis stratified by sex showed that MAFLD had a greater impact in men, and MetS had a greater impact in women regarding the development of CAD. Distinguishing between MetS and/or MAFLD in the presence or absence of type 2 diabetes and according to sex may aid in accurately identifying patients at high risk of cardiovascular disease.


The effect of operative time on surgical-site infection following total shoulder arthroplasty.
Many factors contribute to the risk of surgical-site infection (SSI) following total shoulder arthroplasty (TSA). Operative time is a modifiable factor that may contribute to SSI occurrence after TSA. This study aimed to determine the correlation between operative time and SSI following TSA. By use of the American College of Surgeons National Surgical Quality Improvement Program database, a total of 33,987 patient records were queried from 2006 to 2020 and sorted by operative time and the development of an SSI in the 30-day postoperative period. Odds ratios for the development of an SSI were calculated based on operative time. An SSI developed in the 30-day postoperative period in 169 of the 33,470 patients in this study, resulting in an overall SSI rate of 0.50%. A positive correlation was identified between operative time and the SSI rate. An inflection point was identified at an operative time of 180 minutes, with a significant increase in the rate of SSI occurrence for operative times >180 minutes. Increased operative time was shown to be strongly correlated with an increased risk of SSI within 30 days following surgery, with a significant inflection point at 180 minutes. The target operative time for TSA should be <180 minutes to reduce the risk of SSI.


Kasabach-Merritt syndrome.
Eight infants with hemangiomata associated with severe consumption coagulopathy are reviewed; three died. The presentations and method of management are discussed. The varied response to different modalities of therapy initiated this report and led to a search of the world literature in an attempt to identify the pattern of response, if any, to particular therapy. From our own experience with two cases and from the review of the literature, it appears that radiotherapy alone or in combination with steroids gives a superior overall treatment in terms of reducing the death rate.


Non-competitive inhibition of GABAA responses by a new class of quinolones and non-steroidal anti-inflammatories in dissociated frog sensory neurones.
1. The interaction of a new class of quinolone antimicrobials (new quinolones) and non-steroidal anti-inflammatory agents (NSAIDs) with the GABAA receptor-Cl- channel complex was investigated in frog sensory neurones by use of the internal perfusion and 'concentration clamp' techniques. 2. The new quinolones and the NSAIDs (both 10(-6)-10(-5) M) had little effect on the GABA-induced chloride current (ICI) when applied separately. At a concentration of 10(-4) M the new quinolones, and to a lesser degree the NSAIDs, produced some suppression of the GABA response. 3. The co-administration of new quinolones and some NSAIDs (10(-6)-10(-14) M) resulted in a marked suppression of the GABA response. The size of this inhibition was dependent on the concentration of either the new quinolone or the NSAID tested. The inhibitory potency of new quinolones in combination with 4-biphenylacetic acid (BPAA) was in rank order norfloxacin (NFLX) much greater than enoxacin (ENX) greater than ciprofloxancin (CPFX) much greater than ofloxacin (OFLX), and that of NSAIDs in combination with ENX was BPAA much greater than indomethacin = ketoprofen greater than naproxen greater than ibuprofen greater than pranoprofen. Diclofenac, piroxicam and acetaminophen did not affect GABA responses in the presence of ENX. 4. In the presence of ENX or BPAA, there was a small shift to the right of the concentration-response curve for GABA without any effect on the maximum response. However, the co-administration of these drugs suppressed the maximum of the GABA concentration-response curve, indicating a non-competitive inhibition, for which no voltage-dependency was observed.5. Simultaneous administration of ENX and BPAA also suppressed pentobarbitone (PB)-gated Icl. On the other hand, both PB and phenobarbitone reversed the inhibition of GABA-induced Ic, by coadministration of ENX and BPAA.6. The effect on GABAA responses of co-administration of new quinolones and NSAIDs was not via an interaction with benzodiazepine receptors coupled to the GABAA receptor, since this effect was not reversed by Rol5-1788 or diazepam.7. It is concluded that the co-administration of new quinolones and some of the NSAIDs inhibit GABAergic transmission, and could result in convulsions.


Hereditary abnormalities of the OKT4 human lymphocyte epitope in two families.
The lymphocytes of two unrelated black individuals exhibited no immunofluorescent staining by a monoclonal antibody, OKT4, that reacts with T helper/inducer cells, but the lymphocytes reacted normally with four other monoclonal antibodies that identify T helper cells. Four first-degree relatives of these individuals were available for study. They had a normal proportion of OKT4+ lymphocytes but these cells had approximately half the normal number of OKT4 sites. This abnormality appears to be inherited as an autosomal recessive state.


Distribution of carbon tetrachloride-metabolite(s) to DNase I-sensitive and -resistant chromatin.
The distribution of carbon tetrachloride (CCl4) metabolite(s) to DNase I-sensitive and -resistant regions of mouse hepatic chromatin was determined following incubation of whole chromatin with [14C]CCl4 in the presence of hepatic microsomes and an NADPH-regenerating system. At 2 h of incubation, [14C]CCl4 metabolite(s) bound essentially to the same extent to DNase I-sensitive and -resistant chromatin regions. Binding of [14C]CCl4 metabolite(s) to DNase I-resistant regions, however, increased significantly over the DNase I-sensitive regions when incubation was prolonged to 4 h. This result suggests that CCl4 does not bind preferentially to DNase I-sensitive regions of chromatin.


Direct study of minor extra-virgin olive oil components without any sample modification. 1H NMR multisupression experiment: A powerful tool.
Proton Nuclear Magnetic Resonance (1H NMR) was employed to study monovarietal commercial Spanish extra-virgin olive oils (EVOO) (Arbequina, Arroniz, Cornicabra, Hojiblanca and Picual). Each sample was analyzed by a standard pulse and by an experiment suppressing the main lipid signals, enabling the detection of signals of minor components. The aim was to determine the possibilities of both 1H NMR approaches to characterize EVOO composition, focusing on acyl groups, squalene, sterols, triterpene acids/esters, fatty alcohols, wax esters and phenols (lignans, tyrosol, hydroxytyrosol, oleocanthal, oleacein, oleokoronal, oleomissional, ligstrodials and oleuropeindials), and to determine hydrolysis and oxidation levels. The signal assignments (in deuterated chloroform) are thoroughly described, identifying for the first time those of the protons of esters of phytol and of geranylgeraniol. Correct signal assignment is fundamental for obtaining sound results when interpreting statistical data from metabolomic studies of EVOO composition and adulteration, making it possible to differentiate and classify oils.


Cardiac autonomic activity during sleep in high-altitude resident children compared with lowland residents.
We aimed to characterize heart-rate variability (HRV) during sleep in Andean children native to high altitude (HA) compared with age, gender, and genetic ancestry-similar low-altitude (LA) children. We hypothesized that the hypoxic burden of sleep at HA could induce variation in HRV. As children have otherwise healthy cardiovascular systems, such alterations could provide early markers of later cardiovascular disease. Twenty-six LA (14F) and 18 HA (8F) children underwent a single night of attended polysomnography. Sleep parameters and HRV indices were measured. Linear mixed models were used to assess HRV differences across sleep stage and altitude group. All children showed marked fluctuations in HRV parameters across sleep stages, with higher vagal activity during nonrapid eye movement sleep and greater variability of the heart rate during rapid eye movement (REM). Moreover, HA children showed higher very low-frequency HRV in REM sleep and, after adjusting for heart rate, higher low-to-high frequency ratio in REM sleep compared with children living at lower altitude. We confirmed previous findings of a stage-dependent modulation of HRV in Andean children living at both HA and LA. Moreover, we showed subtle alteration of HRV in sleep in HA children, with intriguing differences in the very low-frequency domain during REM sleep. Whether these differences are the results of an adaptation to high-altitude living, or an indirect effect of differences in oxyhemoglobin saturation remains unclear, and further research is required to address these questions.


Electrical potential changes, H+ translocation and phosphorylation induced by short flash excitation in Rhodopseudomonas sphaeroides chromatophores.
1. The basal decay of the carotenoid shift of chromatophores from photosynthetic bacteria following short flash excitation is approximately biphasic. The decay indicates the dissipation of the transmembrane electrical potential. 2. The H+ efflux following rapid H+ binding after a flash, measured from the colour change of added cresol red, shows very similar kinetics to the carotenoid shift decay suggesting that the dissipation of the electric potential decay is a consequence of the H+ efflux. 3. The electric potential decay is stimulated when the chromatophore suspension is supplemented with ADP and Pi (in either the presence or absence of antimycin A). 4. The stimulated electric potential decay by ADP and Pi has a similar pH dependence to that of phosphorylation in continuous light. 5. The stimulation of the electric potential decay by ADP and Pi is reversed, by aurovertin, an antibiotic which inhibits phosphorylation. 6. The stimulation of the electric potential decay by ADP+Pi is also reversed by the inhibitors oligomycin and venturicidin. These inhibitors, but not aurovertin, also inhibit the fast phase of the decay under non-phosphorylating conditions. 7. Valinomycin accelerates the overall rate of decay of the electric potential, inhibits the ADP and Pi stimulated electric potential decay, and inhibits the flash-induced phosphorylation. The decay rate of the H+ efflux however, is slower in the presence of this ionophore. 8. Nigericin-type ionophores accelerate the overall decay rate of the H+ efflux and inhibit the ADP and Pi stimulated electric potential decay. The basal rate of the electric potential decay is unaffected by treatment with these ionophores. 9. When a coupling factor associated with the chromatophore ATPase is removed from the membrane, both the stimulation of the electric potential decay by ADP and Pi and ADP phosphorylation are inhibtied. Both reactions are completely restored after reconstitution with the crude coupling factor extract. The basal electric potential decay rate is not affected by the removal of coupling factor.


Extinction-resistant attention to long-term conditioned threat is indexed by selective visuocortical alpha suppression in humans.
Previous electrophysiological studies in humans have shown rapid modulations of visual attention after conditioned threat vs. safety cues (<500 ms post-stimulus), but it is unknown whether this attentional prioritization is sustained throughout later time windows and whether it is robust to extinction. To investigate sustained visual attention, we assessed visuocortical alpha suppression in response to conditioned and extinguished threat. We reanalysed data from N = 87 male participants that had shown successful long-term threat conditioning and extinction in self reports and physiological measures in a two-day conditioning paradigm. The current EEG time-frequency analyses on recall test data on Day 2 revealed that previously threat-conditioned vs. safety cues evoked stronger occipital alpha power suppression from 600 to 1200 ms. Notably, this suppression was resistant to previous extinction. The present study showed for the first time that threat conditioning enhances sustained modulation of visuocortical attention to threat in the long term. Long-term stability and extinction resistance of alpha suppression suggest a crucial role of visuocortical attention mechanisms in the maintenance of learned fears.


Generative design for COVID-19 and future pathogens using stochastic multi-agent simulation.
We propose a generative design workflow that integrates a stochastic multi-agent simulation with the intent of helping building designers reduce the risk posed by COVID-19 and future pathogens. Our custom simulation randomly generates activities and movements of individual occupants, tracking the amount of virus transmitted through air and surfaces from contagious to susceptible agents. The stochastic nature of the simulation requires that many repetitions be performed to achieve statistically reliable results. Accordingly, a series of initial experiments identified parameter values that balanced the trade-off between computational cost and accuracy. Applying generative design to a case study based on an existing office space reduced the predicted transmission by around 10% to 20% compared with a baseline set of layouts. Additionally, a qualitative examination of the generated layouts revealed design patterns that may reduce transmission. Stochastic multi-agent simulation is a computationally expensive yet plausible way to generate safer building designs.


Protective action of coenzyme A on paracetamol-induced tissue depletion of glutathione.
Paracetamol toxicity induced in mice a significant depletion in hepatic and renal glutathione concentrations. The administration of CoA in animals prevents the mortality induced by paracetamol and simultaneously prevents the reduction in renal and hepatic glutathione concentrations.


Leptin and mitogen-activated protein kinase (MAPK) in oocytes of sows and gilts.
Leptin is a modulator of oocyte maturation and follicular development in swine. The MAPK are serine/threonine kinases that act as signal transduction pathways in swine ovaries. This study evaluated the presence of leptin, activated MAPK ERK 1/2 and p38 in oocytes of primordial/primary, secondary and tertiary follicles of gilts and sows. Ovaries from ten gilts and ten sows were collected in an abattoir, fixed in 10% formalin and prepared with classical histology methods. For immunohistochemistry, slides were incubated with polyclonal antibodies anti-leptin, anti-phospho ERK1/2 MAPK and anti-phospho p38 MAPK. Leptin immuno-labeling and the presence of activated ERK 1/2 MAPK were more intense for oocytes of sows (P<0.05), whereas p38 MAPK was more active for oocytes of gilts (P<0.05). Although no differences in immunolabeling for leptin and p38 MAPK were observed for oocytes of gilts at distinct follicle developmental stages (P>0.05), immunolabeling was intense for oocytes of sows included in primordial/primary follicles (P<0.05). Thus, leptin and p38 MAPK may be important to start oocyte development.


"When there is no money, that is when I vomit blood": the domino effect and the unfettered lethal exploitation of Black labor on Dominican sugar plantations.
In this article, I utilize the concept of the Plantationocene as an analytical framework to generate a holistic and historical understanding of the present-day struggles of a mostly Haitian migrant workforce on sugar plantations in the Dominican Republic. Inspired by Paul Farmer's methodology, I combine political economy, history, and ethnography approaches to interpret the experiences of sugarcane cutters across historical and contemporary iterations of colonial, post-colonial, and neo-colonial practices over the course of five centuries. My findings elucidate the enduring power of capitalism, implicating corporate and state elites, as the structural scaffolding for acts of racialized violence that condition the life-and-death circumstances of Black laborers on Caribbean plantations to this day. Although today's sugarcane cutters may suffer differently than their enslaved or wage labor ancestors on the plantation, I argue that an unfettered racialized pattern of lethal exploitation is sustained through the structural violence of neoliberalism that links present conditions with the colonial past. Ultimately, this paper contributes understandings of the plantationocene's enduring effects in the global south by demonstrating how imperialist arrangements of capitalism are not a distant memory from the colonial past but instead are present yet hidden and obscured while relocated and reanimated overseas to countries like the Dominican Republic, where American capitalists still exploit Black bodies for profit and power.


The effect of glucose, starch, and pH on growth, enterotoxin and haemolysin production by strains of Bacillus cereus associated with food poisoning and non-gastrointestinal infection.
Brain-Heart Infusion medium, modified by (a) 1.0% w/v glucose supplement, (b) 1.0% w/v soluble starch supplement, (c) pH adjustment to 8.8 or (d) pH adjustment to 5.0, was used to investigate the influence of glucose, starch and pH on growth, enterotoxin and haemolysin production by Bacillus cereus. The four test strains selected for comparison originated from episodes of emetic-syndrome food poisoning, diarrhoeal-syndrome food poisoning, traumatic wound infection and bovine mastitis, respectively. In the presence of either glucose or starch, growth of all strains was found to be near-optimum and accompanied by enhanced enterotoxin production. However, under the moderately acid and alkaline test conditions B. cereus strains exhibited varying degrees of growth inhibition and partial repression of enterotoxin and haemolysin production. In this respect the food-poisoning isolates proved to have greater resistance to adverse pH environments than did the non-gastrointestinal infection isolates.


Specificity of the enzyme-linked immunosorbent assay (ELISA) for antibodies in the sera of specific pathogen-free lambs vaccinated with Pasteurella haemolytica antigens.
Pooled serum from specific pathogen-free (SPF) lambs vaccinated with sodium salicylate extracted (SSE) antigens of Pasteurella haemolytica serotype A1 was shown to contain antibody to other A serotype SSE antigens when tested by the enzyme-linked immunosorbent assay (ELISA). Specific antibody to serotype A1 SSE antigens was demonstrated by absorption of the serum pool with heterologous serotype SSE antigens. The type-specific antigens of serotypes A1 and A9 were prepared by phenol--water extraction (PWE) of their respective SSE antigens. The PWE antigens were examined in a sandwich ELISA where rabbit IgG anti-P. haemolytica A1 cells or A9 cells was used as a coating layer to bind PWE antigens. The specificity of these antigens was demonstrated by marked reduction of reactivity between serum from SPF lambs vaccinated with SSE of serotypes A1 or A9.


Tumors of the optic nerve head.
A variety of primary and secondary tumors can involve the optic nerve head. Examples of primary optic disc tumors include capillary, cavernous and racemose hemangiomas, astrocytomas, and melanocytomas. Secondary optic disc tumors include metastatic carcinoma, leukemia, and those which invade the nerve head from adjacent structures (choroidal melanoma, retinoblastoma, and meningioma). These tumors may produce a variety of clinical features and are discussed in this review. Included also are histopathologic correlations and guidelines for management of the individual entities.


Deciphering the molecular basis of abiotic stress response in cucumber (Cucumis sativus L.) using RNA-Seq meta-analysis, systems biology, and machine learning approaches.
Abiotic stress in cucumber (Cucumis sativus L.) may trigger distinct transcriptome responses, resulting in significant yield loss. More insight into the molecular underpinnings of the stress response can be gained by combining RNA-Seq meta-analysis with systems biology and machine learning. This can help pinpoint possible targets for engineering abiotic tolerance by revealing functional modules and key genes essential for the stress response. Therefore, to investigate the regulatory mechanism and key genes, a combination of these approaches was utilized in cucumber subjected to various abiotic stresses. Three significant abiotic stress-related modules were identified by gene co-expression network analysis (WGCNA). Three hub genes (RPL18, δ-COP, and EXLA2), ten transcription factors (TFs), one transcription regulator, and 12 protein kinases (PKs) were introduced as key genes. The results suggest that the identified PKs probably govern the coordination of cellular responses to abiotic stress in cucumber. Moreover, the C2H2 TF family may play a significant role in cucumber response to abiotic stress. Several C2H2 TF target stress-related genes were identified through co-expression and promoter analyses. Evaluation of the key identified genes using Random Forest, with an area under the curve of ROC (AUC) of 0.974 and an accuracy rate of 88.5%, demonstrates their prominent contributions in the cucumber response to abiotic stresses. These findings provide novel insights into the regulatory mechanism underlying abiotic stress response in cucumber and pave the way for cucumber genetic engineering toward improving tolerance ability under abiotic stress.