Taurine chloramine inhibits PMA-stimulated superoxide production in human neutrophils perhaps by inhibiting phosphorylation and translocation of p47(phox).
Neutrophils produce microbicidal oxidants to destroy the invading pathogens using nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, a membrane-associated enzyme complex that generates superoxide anion (O(2)(-)). Upon stimulation, the cytosolic components of NADPH oxidase, p47(phox) and p67(phox) and the small GTPase Rac move to phagosomal and plasma membranes where they become associated with the membrane components of NADPH oxidase, gp91(phox) and p22(phox) and express enzyme activity. We previously showed that taurine chloramine (Tau-Cl) inhibits O(2)(-) production in mouse peritoneal neutrophils (Kim, 1996). In the present study, we investigated the mechanisms underlying Tau-Cl-derived inhibition on O(2)(-) production using a human myeloid leukemia cell line, PLB-985 cell, which has been differentiated into neutrophil-like cell. Tau-Cl inhibited the phorbol myristate acetate (PMA)-elicited O(2)(-) production as previously observed in murine peritoneal neutrophils. Translocation of p47(phox), p67(phox) and Rac was increased in response to PMA, and Tau-Cl inhibited the PMA-stimulated translocation of p47(phox) and p67(phox) to plasma membrane without affecting the translocation of Rac. In addition, Tau-Cl inhibited the PMA-derived phosphorylation of p47(phox), a requirement for the translocation of cytosolic NADPH oxidase component to the plasma membrane. These results suggest that Tau-Cl inhibits PMA-elicited O(2)(-) production in PLB-985 granulocytes by inhibiting phosphorylation of p47(phox) and translocation of p47(phox) and p67(phox), eventually blocking the assembly of NADPH oxidase complex.


Study protocol of an open-label proof-of-concept trial examining the safety and clinical efficacy of psilocybin-assisted therapy for veterans with PTSD.
Psilocybin-assisted therapy has shown significant promise in treating the cluster of mood and anxiety symptoms that comprise post-traumatic stress disorder (PTSD) but has yet to be tested specifically in this condition. Furthermore, current pharmacological and psychotherapeutic treatments for PTSD are difficult to tolerate and limited in efficacy, especially in the US Military Veteran (USMV) population. This open-label pilot study will examine the safety and efficacy of two psilocybin administration sessions (15 mg and 25 mg), combined with psychotherapy, among USMVs with severe, treatment resistant PTSD. We will recruit 15 USMVs with severe, treatment resistant PTSD. Participants will receive one low dose (15 mg) and one moderate/high dose (25 mg) of psilocybin in conjunction with preparatory and post-psilocybin therapy sessions. The primary safety outcome will be the type, severity and frequency of adverse events and suicidal ideation/behaviour, as measured by the Columbia Suicide Severity Rating Scale. The primary outcome measure for PTSD will be the Clinician Administered PTSD Scale-5. The primary endpoint will be 1 month following the second psilocybin administration session, and the total follow-up time will be 6 months. All participants will be required to provide written informed consent. The trial has been authorised by the Ohio State University Institutional Review Board (study number: 2022H0280). Dissemination of results will occur via a peer-reviewed publication and other relevant media. NCT05554094.


In vivo polarisation sensitive optical coherence tomography for fibrosis assessment in interstitial lung disease: a prospective, exploratory, observational study.
Endobronchial polarisation sensitive optical coherence tomography (EB-PS-OCT) is a bronchoscopic imaging technique exceeding resolution of high-resolution CT (HRCT) by 50-fold. It detects collagen birefringence, enabling identification and quantification of fibrosis. To assess pulmonary fibrosis in interstitial lung diseases (ILD) patients with in vivo EB-PS-OCT using histology as reference standard. Visualisation and quantification of pulmonary fibrosis by EB-PS-OCT. Comparison of EB-PS-OCT and HRCT detected fibrosis with histology, identification of ILD histological features in EB-PS-OCT images and comparison of ex vivo PS-OCT results with histology. Observational prospective exploratory study. Patients with ILD scheduled for transbronchial cryobiopsy or surgical lung biopsy underwent in vivo EB-PS-OCT imaging prior to tissue acquisition. Asthma patients were included as non-fibrotic controls. Per imaged lung segment, fibrosis was automatically quantified assessing the birefringent area in EB-PS-OCT images. Fibrotic extent in corresponding HRCT areas and biopsies were compared with EB-PS-OCT detected fibrosis. Microscopic ILD features were identified on EB-PS-OCT images and matched with biopsies from the same segment. 19 patients were included (16 ILD; 3 asthma). In 49 in vivo imaged airway segments the parenchymal birefringent area was successfully quantified and ranged from 2.54% (no to minimal fibrosis) to 21.01% (extensive fibrosis). Increased EB-PS-OCT detected birefringent area corresponded to increased histologically confirmed fibrosis, with better predictive value than HRCT. Microscopic ILD features were identified on both in vivo and ex vivo PS-OCT images. EB-PS-OCT enables pulmonary fibrosis quantification, thereby has potential to serve as an add-on bronchoscopic imaging technique to diagnose and detect (early) fibrosis in ILD.


Unlocking the promise of mRNA therapeutics.
The extraordinary success of mRNA vaccines against coronavirus disease 2019 (COVID-19) has renewed interest in mRNA as a means of delivering therapeutic proteins. Early clinical trials of mRNA therapeutics include studies of paracrine vascular endothelial growth factor (VEGF) mRNA for heart failure and of CRISPR-Cas9 mRNA for a congenital liver-specific storage disease. However, a series of challenges remains to be addressed before mRNA can be established as a general therapeutic modality with broad relevance to both rare and common diseases. An array of new technologies is being developed to surmount these challenges, including approaches to optimize mRNA cargos, lipid carriers with inherent tissue tropism and in vivo percutaneous delivery systems. The judicious integration of these advances may unlock the promise of biologically targeted mRNA therapeutics, beyond vaccines and other immunostimulatory agents, for the treatment of diverse clinical indications.


The zero exemplar distance problem.
Given two genomes with duplicate genes, Zero Exemplar Distance is the problem of deciding whether the two genomes can be reduced to the same genome without duplicate genes by deleting all but one copy of each gene in each genome. Blin, Fertin, Sikora, and Vialette recently proved that Zero Exemplar Distance for monochromosomal genomes is NP-hard even if each gene appears at most two times in each genome, thereby settling an important open question on genome rearrangement in the exemplar model. In this article, we give a very simple alternative proof of this result. We also study the problem Zero Exemplar Distance for multichromosomal genomes without gene order, and prove the analogous result that it is also NP-hard even if each gene appears at most two times in each genome. For the positive direction, we show that both variants of Zero Exemplar Distance admit polynomial-time algorithms if each gene appears exactly once in one genome and at least once in the other genome. In addition, we present a polynomial-time algorithm for the related problem Exemplar Longest Common Subsequence in the special case that each mandatory symbol appears exactly once in one input sequence and at least once in the other input sequence. This answers an open question of Bonizzoni et al. We also show that Zero Exemplar Distance for multichromosomal genomes without gene order is fixed-parameter tractable in the general case if the parameter is the maximum number of chromosomes in each genome.


Investigation of the Antiangiogenic Properties of Zoledronic Acid by Using Chorioallantoic Membrane Model.
Zoledronic acid (ZA) is a bisphosphonate-derived agent used in osteoporotic clinical pathologies to prevent the development of complications such as fractures and hypercalcemia by regulating bone metabolism. Studies have been conducted on the antiangiogenic efficacy of this agent, which also has other systemic side effects. In this study, the dose-dependent antiangiogenic activity of ZA was investigated on the chorioallantoic membrane model (CAM). Three doses (10-4, 10-5, and 10-6 M concentrations) of drug pellets were prepared with ZA and another pellet was prepared as the positive control group with vascular endothelial growth factor (VEGF) inhibitor agent bevacizumab (10-6 M concentration). Thereafter all pellets were placed on chorioallantoic membranes on the fourth day of egg incubation. All eggs were evaluated for capillary development four days after the drug application. The highest antiangiogenic effect was detected in the positive control group. Moreover, incremental antiangiogenic effects were detected with average scores of .9, 1.1, 1.2 in 10-6, 10-5, and 10-4 M concentrations of ZA groups respectively. Our findings supported that ZA has dose-dependent antiangiogenic effects. This result suggests that different dosing may be required in cases where angiogenesis is therapeutic.


Behavioral effects of the mu-opioid peptide agonists DAMGO, DALDA, and PL017 on locomotor activities.
The relative role of central mu-opioid receptor agonists Tyr-D-Ala-Gly-N-Methyl-Phe-Gly-ol (DAMGO), Tyr-D-Arg-Phe-Lys (DALDA), and Tyr-Pro-MePhe-D-Pro (PL017) (0.00, 0.01, 01, or 1.0 micrograms, ICV) on behavior was investigated in rats for 60 min in activity monitors. DAMGO (0.1 and 1.0 micrograms) and PL017 (1.0 micrograms) resulted in biphasic effects, inhibition followed by hyperactivity for linear locomotor, whereas the 0.01-micrograms dosage was associated with hyperactivity. On the other hand, DALDA (0.1 and 1.0 micrograms) suppressed locomotor activity over the 60-min session.


[Oral, pharyngeal and neck infections in specialized care].
All cases of acute dental, oral and pharyngeal infections that were referred to Mikkeli Central Hospital during a 25-month period were retrospectively analyzed. Thirty-nine percent of the total of 394 cases needed intravenous antibiotics. Tonsillar infections were most prevalent (27%), followed by peritonsillar abscesses (25%) and dental infections (20%). Twenty patients (5%) had cervical or submandibular cellulitis or abscess requiring immediate surgery and an average 8.5 days of in-patient treatment. The most prevalent (45%) bacteriological result was miscellaneous "normal flora". Imminent oropharyngeal infection may require immediate surgery and intravenous antibiotics.


Regression of a cervical spinal mass following highly active antiretroviral therapy (HAART) in child with advanced human immunodeficiency virus (HIV) disease.
This report documents a case of infiltrating cervical spinal mass, most likely a spinal tumor, in a girl with HIV infection that regressed following HAART and without treatment of the tumor or any anti-infectives.


Epidemiology of diabetes in Iran: A scoping review of studies published during 2015-2019.
Proper synthesis of existing epidemiologic studies on diabetes in Iran can guide future research efforts. We aimed to conduct a comprehensive scoping review on all research articles that investigated any aspect of diabetes epidemiology in Iran during 2015-2019. This work was conducted as a part of the Iran Diabetes Research Roadmap and completed under Arksey and O'Malley's framework for scoping reviews. The Scopus and PubMed databases were searched on Feb 15th, 2020. Eligible document types on diabetes epidemiology in the Iranian population, in Persian or English, that published during the 2015-2019 period underwent eligibility assessment. A total of 315 relevant articles were included and further analysis was performed on the original studies (n = 268). Through classifying them into six domains: Diabetes incidence; the prevalence of diabetes and associated factors; the incidence/prevalence of complications/comorbid conditions; mortality/survival; burden; and prediction modeling. In total, 64 (20.3%) papers were published in Q1 journals, and 40 (12.6%) were international collaborations. No clear annual trend was present in the number of published primary or secondary articles, the portion of papers published in Q1 journals, international collaborations or relative domain proportions. Few review articles were found on prediction modeling, mortality or burden (excluding global studies). Our findings show a minor portion of works on diabetic epidemiology in Iran meets the quality standards of Q1 journals. Researchers have neglected some critical subjects and have occasionally fallen for common pitfalls of epidemiologic research. In particular, adhering to established guidelines can help authors implement rigorous methods to develop, validate, and deploy practical clinical prediction models. Researchers should prioritize investigating longitudinally collected data that aid in measuring disease incidence and enable casual inference. The online version contains supplementary material available at 10.1007/s40200-022-01094-0.


Review of the risk of cancer following low and moderate doses of sparsely ionising radiation received in early life in groups with individually estimated doses.
The detrimental health effects associated with the receipt of moderate (0.1-1 Gy) and high (>1 Gy) acute doses of sparsely ionising radiation are well established from human epidemiological studies. There is accumulating direct evidence of excess risk of cancer in a number of populations exposed at lower acute doses or doses received over a protracted period. There is evidence that relative risks are generally higher after radiation exposures in utero or in childhood. We reviewed and summarised evidence from 60 studies of cancer or benign neoplasms following low- or moderate-level exposure in utero or in childhood from medical and environmental sources. In most of the populations studied the exposure was predominantly to sparsely ionising radiation, such as X-rays and gamma-rays. There were significant (p < 0.001) excess risks for all cancers, and particularly large excess relative risks were observed for brain/CNS tumours, thyroid cancer (including nodules) and leukaemia. Overall, the totality of this large body of data relating to in utero and childhood exposure provides support for the existence of excess cancer and benign neoplasm risk associated with radiation doses < 0.1 Gy, and for certain groups exposed to natural background radiation, to fallout and medical X-rays in utero, at about 0.02 Gy.


The estrogen hypothesis of schizophrenia implicates glucose metabolism: association study in three independent samples.
Schizophrenia is a highly heritable complex psychiatric disorder with an underlying pathophysiology that is still not well understood. Metaanalyses of schizophrenia linkage studies indicate numerous but rather large disease-associated genomic regions, whereas accumulating gene- and protein expression studies have indicated an equally large set of candidate genes that only partially overlap linkage genes. A thorough assessment, beyond the resolution of current GWA studies, of the disease risk conferred by the numerous schizophrenia candidate genes is a daunting and presently not feasible task. We undertook these challenges by using an established clinical paradigm, the estrogen hypothesis of schizophrenia, as the criterion to select candidates among the numerous genes experimentally implicated in schizophrenia. Bioinformatic tools were used to build and priorities the signaling networks implicated by the candidate genes resulting from the estrogen selection. We identified ten candidate genes using this approach that are all active in glucose metabolism and particularly in the glycolysis. Thus, we tested the hypothesis that variants of the glycolytic genes are associated with schizophrenia or at least with gender-associated aspects of the illness. We genotyped 185 SNPs in three independent case-control samples of Scandinavian origin (a total of 765 patients and 1274 control subjects). Variants of the mitogen-activated protein kinase 14 gene (MAPK14) and the phosphoenolpyruvate carboxykinase 1 (PCK1) and fructose-1,6-biphosphatase (FBP1) were nominal significantly associated with schizophrenia, and several haplotypes within enolase 2 gene (ENO2) consist of the same SNP allele having elevated risk of schizophrenia. Importantly, we find no evidence of stratification due to nationality or gender. Several gene variants in the Glycolysis were associated with schizophrenia in three independent samples. However, the findings are weak and not resistant to correction for multiple testing, which may indicate that they are either spurious or may relate to a particular subtype or aspect of the illness.


MRP2 and the Transport Kinetics of Cysteine Conjugates of Inorganic Mercury.
Human exposure to mercuric species occurs regularly throughout the world. Mercuric ions may accumulate in target cells and subsequently lead to cellular intoxication and death. Therefore, it is important to have a thorough understanding of how transportable species of mercury are handled by specific membrane transporters. The purpose of the current study was to characterize the transport kinetics of cysteine (Cys)-S-conjugates of inorganic mercury (Cys-S-Hg-S-Cys) at the site of the multidrug resistance-associated transporter 2 (MRP2). In order to estimate the maximum velocity (V max) and Michaelis constant (K m) for the uptake of Cys-S-Hg-S-Cys mediated by MRP2, in vitro studies were carried out using radioactive Cys-S-Hg-S-Cys (5 μM) and inside-out membrane vesicles made from Sf9 cells transfected with MRP2. The V max was estimated to be 74.3 ± 10.1 nmol mg protein-1 30 s-1 while the K m was calculated to be 63.4 ± 27.3 μM. In addition, in vivo studies were utilized to measure the disposition of inorganic mercury (administered dose 0.5 μmol kg-1 in 2 mL normal saline) over time in Wistar and TR¯ (Mrp2-deficient) rats. These studies measured the disposition of mercuric ions in the kidney, liver, and blood. In general, the data suggest that the initial uptake of mercuric conjugates into select target cells is rapid followed by a period of slower uptake and accumulation. Overall, the data indicate that MRP2 transports Cys-S-Hg-S-Cys in a manner that is similar to that of other MRP2 substrates.


The anti-cancer effect and mechanism of animal scale-derived extract on malignant melanoma cells.
Melanoma is a type of cancer with abnormal proliferation of melanocytes and is one of the most diagnosed cancer types. In traditional Chinese medicine, pangolin scales have been used to treat various diseases, including human cancers. However, its efficacy has not been scientifically proven. Here we studied the anticancer effect and mechanism of pangolin scale extract (PSE) on melanoma cell lines using scientific approaches. Our cell viability assay shows that PSE exhibits up to approximately 50-80% inhibition on SK-MEL-103 and A375 melanoma cell lines. Mechanically, PSE inhibits melanoma cell proliferation, migration, and causes changes in cell morphology. The apoptosis assay showed a significant chromosomal condensation inside the PSE-treated melanoma cells. The sequencing and analysis of A375 melanoma cell transcriptomes revealed 3077 differentially expressed genes in the 6 h treatment group and 8027 differentially expressed genes in the 72 h treatment group. Transcriptome analysis suggests that PSE may cause cell cycle arrest in melanoma cells and promote apoptosis mainly by up-regulating the p53 signaling pathway and down-regulating the PI3K-Akt signaling pathway. In this study, the anticancer effect of PSE was demonstrated by molecular biological means. PSE shows a significant inhibition effect on melanoma cell proliferation and cell migration in vitro, causes cell cycle arrest and promotes apoptosis through p53 and PI3K-AKT pathways. This study provides better insights into the anti-cancer efficacy and underlying mechanism of PSE and a theoretical basis for mining anticancer compounds or the development of new treatments for melanoma in the future. It is worth noting that this study does not advocate the use of the pangolin scale for disease treatment, but only to confirm its usefulness from a scientific research perspective and to encourage subsequent research around the development of active compounds to replace pangolin scales to achieve the conservation of this endangered species.


Changing the paradigm for pesticide resistance management.
Collaborative action on the part of all stakeholders in pest management is essential to effectively address the challenges of pesticide resistance. The US Environmental Protection Agency (EPA), through its Pesticide Program Dialogue Committee, recently posted a report on pesticide resistance management and the role the Agency can play in these efforts. In this Perspective, we commend the Agency for acknowledging these needs, and encourage implementation of the recommendations. We urge all stakeholders to follow the example set by the EPA to engage openly, listen to other stakeholders, and determine their role as part of the broader community that is needed to address the challenges of resistance. Our contention is that pesticide resistance will continue to escalate until all stakeholders evaluate their roles in resistance management and work together as a community to influence effective management. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Effects of tolerogenic conjugates in a canine model for reaginic hypersensitivity. I. suppression of hapten-specific IgE antibody response.
Intraperitoneal administration to dogs of conjugates consisting of the 2,4-dinitrophenyl (DNP) groups coupled to nonimmunogenic macromolecules such as the copolymer of D-glutamic acid and D-lysine (DNP16-DGL) prior to sensitization with DNP2-ovalbumin led to the development of hapten-specific tolerance with respect to the IgE antibody response. Administration of these same conjugates to sensitized dogs resulted in complete abrogation of the ongoing anti-DNP IgE antibody production. A similar hapten-specific suppression of the ongoing anti-DNP response was also observed using the conjugates of DNP9-canine gamma globulins, and the tolerogenic effect was dose-dependent. The state of hapten-specific immunosuppression induced by these two types of tolerogenic conjugates was maintained despite repeated booster injections of the sensitizing antigens at biweekly inervals.


Fournier's gangrene: evaluation of 68 patients and analysis of prognostic variables.
Fournier's gangrene (FG) is a rapidly progressing acute gangrenous infection of the anorectal and urogenital area. The objectives of this study were to investigate patients with FG and to determine risk factors that affect mortality. Retrospective clinical study. Clinical presentations and outcomes of surgical treatments were evaluated in 68 patients with FG. Chi-square, Student's t -test, and logistic regression test. Mean age of patients was 54 and female-to-male ratio was 9:59. Among the predisposing factors, diabetes mellitus (DM) was the most common ( n =24, 35.3%), and sepsis on admission was detected in 31 (45.6%) and 15 (22.1%) patients, respectively. Seven (10.3%) patients died. Using logistic regression test, Fournier's Gangrene Severity Index (FGSI)> 9, DM and sepsis on admission were found as prognostic factors. FG has a high mortality rate, especially in patients with DM and sepsis. An FGSI value> 9 indicates high mortality rate.


The influence of an IL-4 variable number tandem repeat (VNTR) polymorphism on breast cancer susceptibility.
Breast cancer (BC) is one of the most widespread cancers globally. Understanding the etiology of BC may help in determining the various risk factors involved in its malignancy. Certain genetic mutations are considered to play a key role in increasing the risk of BC. In this study, we explored the correlation between a variable number tandem repeat (VNTR) polymorphism in the IL-4 gene and BC. PCR and subsequent gel electrophoresis were used to genotype this variant in 360 Jordanian women (180 BC patients and 180 controls). In addition, phenotype-genotype analysis was carried out. Our findings illustrate that there is no significant relationship between the variant genotypes in the IL-4 gene and BC among Jordanian females. Other than body mass index and tumor differentiation (p< 0.05), none of the clinical and pathological parameters of BC patients exhibited any association with the variant genotypes. From this study, we propose that the IL-4 genetic variant does not impact BC development and progression but that it could influence the disease prognosis.


The intensity of breast cancer patients' relationships with their surgeons after the first meeting: Evidence that relationships are not 'built' but arise from attachment processes.
Cancer clinicians are exhorted to build clinical relationships with their patients over time using patient-centred communication skills. An alternative view is that patients' sense of relationship is a response to clinicians' expertise and authority and therefore is normally present from the start. We measured the intensity of breast cancer patients' sense of relationship with their surgeon after their first brief, diagnostically focused meeting in order to compare it with published reports from patients in other types and stages of clinical relationship. Women (N = 133) over 18 years old and due to undergo surgery for primary breast cancer were recruited consecutively from pre-operative clinics. Patients reported the intensity of their relationship with the surgeon on a standardised questionnaire (Working Alliance Inventory). We compared their ratings with published reports over the last 15 years, in which patients in other types of clinical relationship completed the same questionnaire. Patients' alliance with their surgeons was very high (mean 6.13, 95% CI: 5.99, 6.27, on a 1-7 scale), and at 90(th) percentile when compared with scores from other settings, including those characterized by many hours of talk addressing patients' emotional needs. Patients with breast cancer feel an intense sense of relationship with the surgeon from the first meeting, consistent with the view that their sense of relationship arises primarily from their recognition of the surgeon's expertise and authority. The challenge for surgeons is therefore not usually to 'build a relationship' but to support the sense of relationship that patients have from the start.


New computer-guided scanner for improving CO2 laser-assisted microincision.
The objective was to clinically test a new computer-guided scanner designed for CO2 laser-assisted microincision. The scanner-assisted beam travels across the target as a straight or curved incision line. Line length and beam penetration can be adjusted. The studied population, 155 cases, encompassed benign lesions as well as early cancers of the larynx. Operating time was compared with that required for similar operations performed with the Acuspot micromanipulator. Laser-produced coagulation thickness at the incision was measured on 41 operative specimens. The scanner-assisted incision and dissection were more accurate and required up to 30% less time than with a manually guided beam. Postoperative follow-up was straightforward. The coagulation thickness was less than 10 microm for phonomicrosurgery and less than 20 microm for other surgical procedures. The scanner-assisted incision is more accurate than that attained manually.


Cytogenetic observations in a human gastric leiomyosarcoma.
The chromosomes of a human gastric leiomyosarcoma were studied in preparations from short-term cultures. The tumor had a triploid-near-triploid modal population characterized by extensive numerical and structural changes. Of these deviations, del(1)(p12-13), monosomy 14, and underrepresentation of chromosomes 18 and 22 were abnormalities in common with two of the three previously studied leiomyosarcomas of the small bowel.


Cell-mediated immunity, Epstein-Barr virus and nasopharyngeal carcinoma.
Cellular immunity is apparently important in host defenses against cancer. A growing body of information on CMI to EBV is here reviewed, providing a strong basis for studies of such reactivity in NPC. Present work suggests that CMI responses to virus- and tumour-associated antigens may have implications for etiology, diagnosis and treatment.


Effect of cognitive load and working memory capacity on the efficiency of discovering better alternatives: A survival analysis.
Why do humans attempt to discover better alternatives to solve a problem even when they know the way to solve it? This question is related to the flexibility of thinking and is the subject of studies on the Einstellung effect. This study focuses on cognitive load for familiar trained procedure as a factor that influences the discovery of alternatives in Einstellung situations, where the problem can be solved using a trained procedure. Many studies on creative problem solving and strategy selection demonstrate that cognitive load for facilitates the discovery of alternatives. However, findings are inconsistent regarding Einstellung situations. We argue that the reason for such inconsistent results were the use of manipulations such as the double task, which both load on the trained and alternative procedure and the lack of perspective on efficiency in analysis. Therefore, we examine the relationship between cognitive load manipulated by the complexity of the trained procedure and time-based performance measured by the number of trials prior to finding alternatives. The results illustrate that higher cognitive load increased the efficiency of discovery of alternatives and that this effect was significant for participants with high working memory capacity. This study provides empirical evidence that high cognitive load for trained procedure facilitates the discovery of alternatives and suggests the importance of considering temporal properties, such as efficiency, when examining the effects of working memory on problem solving, which requires cognitive flexibility.


Effect on growth of children with cardiac dysrhythmias treated with amiodarone.
We report the results of treatment with amiodarone in nine children with dysrhythmias resistant to conventional drugs, namely, one with ventricular tachycardia, two with atrial tachycardia, one with junctional tachycardia, three with reciprocal rhythm tachycardia, and two with Wolff-Parkinson-White syndrome. The initial dose was 800 mg/1.73 m2, administered for two weeks, followed by half the dose for five days a week. The duration of the treatment varied from nine months to 19 months (mean duration, 13 months). Patients were followed up for a period ranging between nine and 33 months (mean period, 17 months). A complete remission was obtained in 56% of patients and partial success in 46%. The following side effects were detected: photosensitization in two; effect on weight, height, growth velocity, and thyroid hormones in three, six, five, and six, respectively; and acceleration in bone age in three. These effects were observed from two to nine months after the beginning of treatment. They persisted for 5-18 months after treatment had been suspended. The main side effect of amiodarone in children is presumably initial hypothyroidism, followed by a biological hyperthyroid reaction. For these reasons we suggest that amiodarone should be restricted as an alternative drug for resistant critical dysrhythmias and be used only for a limited period of two years.


[Effect of special regulated respiratory exercises on autonomic support of functional state of the cardio-vascular system].
48 healthy people have been observed to determine the influence of individually chosen special regulated respiratory exercises on functional state of the cardio-vascular system. The findings showed that special regulated respiratory exercises considerably enhance vegetative supply to the cardio-vascular system thus increasing its functional state.


Estimation and mapping of uranium content of geological units in France.
In France, natural radiation accounts for most of the population exposure to ionizing radiation. The Institute for Radiological Protection and Nuclear Safety (IRSN) carries out studies to evaluate the variability of natural radioactivity over the French territory. In this framework, the present study consisted in the evaluation of uranium concentrations in bedrocks. The objective was to provide estimate of uranium content of each geological unit defined in the geological map of France (1:1,000,000). The methodology was based on the interpretation of existing geochemical data (results of whole rock sample analysis) and the knowledge of petrology and lithology of the geological units, which allowed obtaining a first estimate of the uranium content of rocks. Then, this first estimate was improved thanks to some additional information. For example, some particular or regional sedimentary rocks which could present uranium contents higher than those generally observed for these lithologies, were identified. Moreover, databases on mining provided information on the location of uranium and coal/lignite mines and thus indicated the location of particular uranium-rich rocks. The geological units, defined from their boundaries extracted from the geological map of France (1:1,000,000), were finally classified into 5 categories based on their mean uranium content. The map obtained provided useful data for establishing the geogenic radon map of France, but also for mapping countrywide exposure to terrestrial radiation and for the evaluation of background levels of natural radioactivity used for impact assessment of anthropogenic activities.


Deleterious effect of gestagens from wastewater effluent on fish reproduction in aquatic environment: A review.
Gestagens are common pollutants accumulated in the aquatic ecosystem. Gestagens are comprised of natural gestagens (i.e. progesterone) and synthetic gestagens (i.e. progestins). The major contributors of gestagens in the environment are paper plant mill effluent, wastewater treatment plants, discharge from pharmaceutical manufacturing, and livestock farming. Gestagens present in the aquatic environment interact with progesterone receptors and other steroid hormone receptors, negatively influencing fish reproduction, development, and behavior. In fish, the gonadotropin induces 17α, 20β-dihydroxy-4-pregnen-3-one (DHP) production, an important steroid hormone involved in gametogenesis. DHP interacts with the membrane progestin receptor (mPR), which regulates sperm motility and oocyte maturation. Gestagens also interfere with the hypothalamic-pituitary-gonadal (HPG) axis, which results in altered hormone levels in fish. Moreover, recent studies showed that even at low concentrations exposure to gestagens can have detrimental effects on fish reproduction, including reduced egg production, masculinization, feminization in males, and altered sex ratio, raising concerns about their impact on the fish population. This review highlights the hormonal regulation of sperm motility, oocyte maturation, the concentration of environmental gestagens in the aquatic environment, and their detrimental effects on fish reproduction. However, the long-term and combined impacts of multiple gestagens, including their interactions with other pollutants on fish populations and ecosystems are not well understood. The lack of standardized regulations and monitoring protocols for gestagens pollution in wastewater effluent hampers effective control and management. Nonetheless, advancements in analytical techniques and biomonitoring methods provide potential solutions by enabling better detection and quantification of gestagens in aquatic ecosystems.


Selection for chlorpyrifos resistance in Liriomyza sativae Blanchard: Cross-resistance patterns, stability and biochemical mechanisms.
The vegetable leafminer (VLM), Liriomyza sativae (Diptera: Agromyzidae) is a serious pest of vegetable crops and ornamentals worldwide. In cropping systems with inappropriate management strategies, development of resistance to insecticides in leafminers is probable. Chlorpyrifos is a commonly used pesticide for controlling leafminers in Iran, but resistance to this insecticide in leafminers has not been characterized. In order to develop strategies to minimize resistance in the field and greenhouse, a laboratory selected chlorpyrifos resistant strain of L. sativae was used to characterize resistance and determine the rate of development and stability of resistance. Selecting for resistance in the laboratory after 23 generations yielded a chlorpyrifos resistant selected strain (CRSS) with a resistance ratio of 40.34, determined on the larval stage. CRSS exhibited no cross-resistance to other tested insecticides except for diazinon. Synergism and biochemical assays indicated that esterases (EST) had a key role in metabolic resistance to chlorpyrifos, but glutathione S-transferase (GST) and mixed function oxidase (MFO) were not mediators in this resistance. In CRSS acetylcholinesterase (AChE) was more active than the susceptible strain, Sharif (SH). AChE in CRSS was also less sensitive to inhibition by propoxur. The kinetics parameters (Km and Vmax) of AChE indicated that affinities and hydrolyzing efficiencies of this enzyme in CRSS were higher than SH. Susceptibility to chlorpyrifos in L. sativae was re-gained in the absence of insecticide pressure. Synergism, biochemical and cross-resistance assays revealed that overactivity of metabolic enzymes and reduction in target site sensitivity are probably joint factors in chlorpyrifos resistance. An effective insecticide resistance management program is necessary to prevent fast resistance development in crop systems.


Capturing intracellular Ca2+ dynamics in computational models of neurodegenerative diseases.
Many signaling pathways crucial for homeostatic regulation, synaptic plasticity, apoptosis and immune response depend on Ca2+. Ca2+ dysregulation disrupts normal function of neurons and neuronal networks. This causes severe motor and cognitive disabilities. Understanding how Ca2+ dysregulation triggers disease onset and progression, and affects downstream processes, can help identify targets for treatments. Because of intermingling of molecular pathways, dissecting the role of individual mechanisms and establishing causality is very challenging. Computational models provide a way to decipher these processes. I review some computational models with Ca2+ dynamics to illustrate their predictive power, and note where extending those models to capture multiscale interaction of Ca2+ dependent molecular pathways can be useful for therapeutic and drug discovery purposes.


Genome hunting of carbonyl reductases from Candida glabrata for efficient preparation of chiral secondary alcohols.
In this work, genome hunting strategy was adopted in screening for reductases from Candida glabrata. A total of 37 putative reductases were successfully expressed in E. coli BL21(DE3). A substrate library containing 32 substrates was established for characterization of each reductase by average specific activity and Shannon-Wiener index. Among them, Cg26 was identified with the highest efficiency and wider substrate spectrum in the reduction of prochiral ketones, with average activity and Shannon-Wiener index of 8.95U·mg-1 and 2.82. Cg26 is a member of 'extended' short chain dehydrogenase/reductase superfamily. Ni2+ could improve its activity. As much as 150g·L-1 ethyl 2-oxo-4-phenylbutyrate could be completely converted by 10g·L-1 Cg26. This study provides evidence for this newly identified Cg26 in the preparation of chiral secondary alcohols.


Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study.
Evidence on the effectiveness of highly active antiretroviral therapy (HAART) for HIV-infected individuals is limited. Most clinical trials examined surrogate endpoints over short periods of follow-up and there has been no placebo-controlled randomised trial of HAART. Estimation of treatment effects in observational studies is problematic, because of confounding by indication. We aimed to use novel methodology to overcome this problem in the Swiss HIV Cohort Study. Patients were included if they had been examined after January 1996, when HAART became available in Switzerland, were not on HAART, and were free of AIDS at baseline. Cox regression models were weighted to create a statistical population in which the probability of being treated at each time point was unrelated to prognostic factors. Low CD4 counts and increasing HIV-1 viral load were associated with increased probability of starting HAART. Overall hazard ratios were 0.14 (95% CI 0.07-0.29) for HAART compared with no treatment, and 0.49 (0.31-0.79) compared with dual therapy. Compared with no treatment, HAART became more beneficial with increasing time since initiation but was less beneficial for patients whose presumed mode of transmission was via intravenous drug use (hazard ratio 0.27, 0.12-0.61) than for other patients (0.08, 0.03-0.19). Our results, which are appropriately controlled for confounding by indication, are consistent with reported declines in rates of AIDS and death in developed countries, and provide a context in which to consider adverse effects of HAART.


Postpartum hemoptysis as presenting sign of longstanding vasculitis.
We present the case of a 26-year-old postpartum patient who presented with an episode of desaturation and hemoptysis on postpartum day three after an uncomplicated spontaneous vaginal delivery. The patient came to our attention in the postpartum area after she experienced massive hemoptysis and we were called by the obstetric team. The patient was subsequently intubated, mechanically ventilated, and underwent bronchoscopy, demonstrating diffuse alveolar hemorrhage. She was brought to the intensive care unit, placed on high-dose steroids and plasmapheresis was initiated. Her intensive care unit course was complicated by acute respiratory distress syndrome, acute kidney injury and a pulmonary embolism, but she recovered well and was discharged on postpartum day 23. This report describes a rare case of medium vessel vasculitis diagnosed in the peripartum period, and describes the diagnostic dilemmas underlying making a rare diagnosis, and the difficulties initiating appropriate therapy in a postpartum patient.


Modified vaccinia virus Ankara delivers a robust surrogate marker for immune monitoring to sarcoma cells even if cells are being exposed to chemotherapy and heat treatment.
Adding hyperthermia to chemotherapy improved the clinical outcome of patients with high risk soft tissue sarcoma. Further improvement might be possible if combined with vaccination strategies. As no sarcoma-associated antigens are known, the ectopic expression of a surrogate marker for which immune monitoring tools are available, is envisaged. We tested surrogate marker transfer into sarcoma cells in vitro using modified vaccinia virus Ankara (MVA), which has well established clinical safety. We examined its robustness against standard sarcoma treatment modalities, such as ifosfamide and hyperthermia. We transduced sarcoma cell lines and primary tumour cells from sarcoma patients with MVA encoding the human tyrosinase gene (MVA-hTyr). Kinetics of tyrosinase expression and the potency to activate tyrosinase-specific cytotoxic T cells were assessed. In addition cells were exposed to chemotherapy and heat, imitating the clinical setting. Tyrosinase was ectopically expressed in sarcoma cells. Infected cells presented tyrosinase epitopes for T cell recognition even if exposed to ifosfamide/heat. As sarcoma patients receive surgery up front or after neoadjuvant systemic chemotherapy/hyperthermia, tumour material is generally available. Our data document that primary sarcoma cells can be infected with MVA-hTyr in vitro and antigen presentation is not affected by ifosfamide or heat treatment. Infected cells can serve as a source for vaccine preparation. MVA-hTyr infection of tumour cells lacking defined antigens is a feasible system to introduce a robust surrogate marker to provide an immune monitoring marker for assessing the induction of antigen-specific T cell activation.


Determination of Pd, Rh, Pt, Au in road dust by electrothermal vaporization inductively coupled plasma mass spectrometry with slurry sampling.
Inductively coupled plasma mass spectrometry coupled with ultrasonic slurry sampling electrothermal vaporization (USS-ETV-ICP-MS) has been applied to determine Pd, Rh, Pt and Au in 0.5% m/v slurries of several road dust samples. 2% m/v ammonium pyrrolidine dithiocarbamate (APDC) was used as the modifier to enhance the ion count. The influence of instrument operating conditions, slurry preparation and interferences on the ion count was reported. This method has been applied to the determination of Pd, Rh, Pt and Au in BCR 723 Road Dust and NIST SRM 2709 San Joaquin Soil reference materials and two road dust samples collected locally. The analysis results of the standard reference materials agreed with the certified values. Precision between sample replicates was better than 10% for all the determinations. The method detection limits estimated from standard addition curves were 0.9, 0.4, 0.6 and 0.4ngg(-1) for Pd, Rh, Pt and Au, respectively, in original dust samples.


Attenuation of perfluoropolymer fume pulmonary toxicity: effect of filters, combustion method, and aerosol age.
Thermal decomposition products of some perfluorinated polymers are toxic to experimental animals in small-scale combustion toxicity tests; the toxicity is dependent upon the heating procedure, combustion temperature, and other experimental conditions. In the current studies we investigated the time course of fume generation and exposure on pulmonary effects in rats following a 30-min exposure to perfluoropolymer decomposition products (i.e., fume concentration = 0.2 mg/m3 of tetrafluoroethylene/hexafluoropropylene copolymer (FEP)) pyrolyzed with either static or dynamic airflows. In the first set of experiments, five different groups of rats were exposed to FEP fumes in a static combustion toxicity test system. Three groups were exposed to unfiltered FEP fumes during 0- to 15-, 15- to 30-, and 0- to 30-min intervals, respectively, and one to a filtered (particle-free) atmosphere of combusted FEP for 30 min. Sham-exposed rats constituted the control group. Immediately after exposure, the rats were sacrificed and their lungs weighed and lavaged or perfused to assess indices of cytotoxicity. Our results showed that lung weights, markers of inflammation, and pulmonary hemorrhage and alkaline phosphatase, beta-glucuronidase, lactate dehydrogenase, and protein levels in bronchoalveolar lavage fluids were significantly elevated in all unfiltered FEP-exposed groups compared to those in either the rates exposed through filters or controls (P less than 0.01). In a second set of experiments using a dynamic pyrolysis toxicity test system, rats were exposed for 30 min to FEP-pyrolyzed fumes which were either freshly generated or aged for 1 or 5 min prior to delivery to the animal's breathing zone. Subsequently, lung cytotoxicity parameters were measured. Rats exposed directly to the fresh fumes demonstrated toxic effects consistent with those described above (P less than 0.01), but the pulmonary toxicity of aged (i.e., 1 or 5 min delay) FEP fumes was diminished in a time-dependent manner, suggesting that the toxicant was unstable. Histopathological studies correlated with biochemical results and revealed that inhalation of unfiltered or freshly generated FEP fumes produced a severe lung injury characterized by the development of alveolar and interstitial edema, intraalveolar hemorrhage, congestion, and fibrin deposition. Electron microscopy studies demonstrated severe damage to terminal bronchiolar cells and detachment of Type I epithelial and endothelial cells in pulmonary regions. The severity of pathology observed in lungs of rats exposed to 1-min aged fumes was intermediate between unfiltered/unaltered fume-exposed animals and sham controls. The results of these studies demonstrate that the lung toxicity of perfluoropolymer fumes is associated with the aerosol phase generated in perfluoropolymer pyrolysis.


Microplastic pollution in urban green-belt soil in Shihezi City, China.
The problems are associated with microplastic (MP) pollution of global concern. However, little is known about the pollution characteristics and sources of MPs in urban green-belt soils. Therefore, this study investigated MP pollution in 11 sampling sites (22 green belts) in Shihezi City. The results showed that the abundance of MPs (0.02-5.00 mm) ranged from 287 ± 100 items/kg dw to 3227 ± 155 items/kg dw (mean + SD). Fibers (69.9%) accounted for the majority of MPs, and the MPs were mainly black (36.7%) and 0.02-0.5 mm (64.8%). The main types of MPs were polystyrene (PS) and polyethylene (PE). Compared with agricultural soil, the color and composition of green-belt soil MPs are diverse, which means that the source of green-belt soil MPs is more diverse. In different types of green-belt soil, MP pollution of industrial green land is more serious. Through cluster analysis and spatial distribution, fragments and fibers were found to have similar sources, mainly originating from food and textile industrial activities. This study provides important information for revealing MP pollutions in urban green-belt soils.


Rigid Fixation of the Pediatric Facial Skeleton.
Pediatric facial fractures are uncommon, and fortunately, the majority can be managed with conservative measures. Rigid fixation of the pediatric facial skeleton can potentially be associated with delayed hardware issues and growth inhibition. When appropriate, resorbable fixation is most commonly used for this purpose. Titanium plates and screws are advantageous when rigid fixation is a priority because properly placed hardware that respects natural suture lines is not thought to significantly inhibit growth. Furthermore, titanium fixation may be removed following healing.


Immune response of chimpanzee to purified melanoma 250 kilodalton tumor-associated antigen.
Melanoma high molecular weight tumor-associated antigen (TAA), having a molecular weight of 250 kilodaltons (Kd), was purified from a crude cell membrane extract through a combination of lectin affinity, immunoadsorption, and high performance liquid molecular filtration chromatography. Compared to the starting extract, purified TAA was 600-fold higher in TAA activity per microgram of protein. Purified TAA was used to immunize a chimpanzee and the resulting antiTAA immune response was evaluated. Postimmune chimpanzee serum reacted in solid phase radioimmunoassay against purified TAA with a titer in excess of 100,000. In contrast, preimmune serum had a titer of less than 100 in the same assay. By immunoprecipitation analysis, we were able to demonstrate reactivity of the chimpanzee immune serum with a 250 Kd TAA in spent culture medium from melanoma cells metabolically labeled with 35S-methionine and with iodinated purified 250 Kd TAA. Reactivity of the chimpanzee antiserum for the 250 Kd TAA was confirmed in blocking and reciprocal immunodepletion studies using murine monoclonal antibody 9.2.27. These studies suggest that the 250 Kd TAA defined by murine monoclonal antibodies may prove to be immunogenic in man and that manipulation of the immune response to this TAA might be used to the clinical benefit of the patient.


Diagnostic yield of non-invasive imaging in patients following non-traumatic out-of-hospital sudden cardiac arrest: A systematic review.
To review data for non-invasive imaging in the diagnosis of non-traumatic out-of-hospital cardiac arrest (OHCA). We searched MEDLINE, EMBASE, Cochrane library, and clinicaltrials.gov databases from inception to January 2017 for studies utilizing non-invasive imaging to identify potential causes of OHCA [computed tomography (CT), ultrasound including echocardiography, and magnetic resonance (MRI)]. Inclusion criteria were the following: (1) randomized control trials, cohort studies or observational studies; (2) contained a population ≥18 years old with non-traumatic OHCA who underwent diagnostic imaging with CT, MRI, echocardiography, or abdominal ultrasound; (3) imaging was obtained for diagnostic purposes; (4) patients were alive or were undergoing cardiopulmonary resuscitation at the time of imaging; (5) contained potential causes of OHCA. Endpoints studied were the number of potential OHCA causes identified, diagnostic accuracy measures (sensitivity, specificity, positive and negative predictive values), and diagnostic utility (number of imaging findings with reported changes in clinical management). Of the total 5722 studies identified, 17 (0.3%) met inclusion criteria. The majority of studies assessed the utility of CT in OHCA (n=10), and potential causes of OHCA were found in 8-54% of patients following head, abdominal and/or chest CT. Only 1/17 (6%) studies reported diagnostic accuracy measures, and 9/17 (53%) studies included a time to imaging criteria within 24h. Although non-invasive imaging is commonly performed in patients after OHCA, its diagnostic utility remains poorly characterized. Prospective studies are needed for appropriate imaging selection and their potential impact on treatment and outcome.


Catalytic Cyclization of o-Alkynyl Phenethylamines via Osmacyclopropene Intermediates: Direct Access to Dopaminergic 3-Benzazepines.
A novel osmium-catalyzed cyclization of o-alkynyl phenethylamines to give 3-benzazepines is reported. The procedure allows the straightforward preparation of a broad range of dopaminergic 3-benzazepine derivatives. Mechanistic investigations revealed that the process takes place via osmacyclopropene intermediates, which were isolated and characterized by X-ray crystallography.


Morphologically and immunohistochemically undifferentiated gastric neoplasia in a patient with multiple metastatic malignant melanomas: a case report.
Malignant melanoma is a neoplasia which frequently involves the gastrointestinal tract (GIT). GIT metastases are difficult to diagnose because they often recur many years after treatment of the primary cutaneous lesion and also manifest clinically at an advanced stage of the neoplasia. Furthermore, GIT metastases can appear in various morphological forms, and therefore immunohistochemistry is often useful in distinguishing between a malignant melanoma and other malignancies. We report the case of a 60-year-old man with a multiple metastatic melanoma who underwent an upper endoscopy to clarify the possible involvement of the gastric wall with a mass localized in the upper abdomen involving the pancreas and various lymph nodes, which was previously described with computed tomography. Clinically, the patient reported a progressive loss of appetite, nausea and vomiting. The upper endoscopy and histological examination revealed a gastric location of an undifferentiated neoplasm with an absence of immunohistochemical characteristics referable to the skin malignant melanoma that was removed previously. The present case report shows the difficulty in diagnosing a metastatic melanoma in the GIT and therefore, it seems worthwhile to consider metastatic malignant melanoma in the differential diagnosis of undifferentiated neoplasia.


Daytime sleepiness: quantification of a behavioral state.
A neurophysiological technique that quantifies drowsiness as the speed of falling asleep at intervals across a day is used to identify patterns of sleepiness/alertness. The Multiple Sleep Latency Test (MSLT) reveals a daily biphasic organization of sleepiness that is affected in predictable ways by the length and continuity of nocturnal sleep on one or several nights, and by maturation, aging, sleep pathology, and drug ingestion. The systematic nature of these relationships provides impetus to efforts examining the neurobiological mechanisms subserving the delicate balance of sleep and wakefulness.


Omalizumab Treatment in Uncontrolled Asthma and CRSwNP Patients, with Previous Endoscopic Sinus Surgery, to Improve Quality of Life and Endoscopic Outcomes: a Two-Year Real-Life Study.
Despite molecular underlying advances, limited and divergent data on monoclonal antibodies (mAb) therapy in chronic rhinosinusitis with nasal polyps (CRSwNP) make further analysis necessary. The objective of this study is to evaluate the effect of omalizumab as an adjunct to endoscopic sinus surgery (ESS) on the treatment of CRSwNP under real-life conditions. Since the introduction of omalizumab, as the first biologic agent for the treatment of diseases such as severe allergic asthma, different studies have demonstrated an effect of omalizumab on CRSwNP, with significant improvements in sinonasal symptoms and endoscopic scores. The high efficacy derived from mAb therapy and the need for ESS prior to mAb recommended by guidelines, has led to compare both therapeutic alternatives, finding discrepancies in their effect on quality of life (QoL) and complementary tests outcomes. Patients with moderate-to-severe asthma with clinical criteria for omalizumab indication, and coexistent CRSwNP disease, were selected for a non-randomized interventional retrospective study into four treatment subgroups. Measures were analyzed and compared between groups and over time at the baseline, 16 weeks and 1 and 2 years after treatment. Omalizumab treatment in patients with previous ESS exhibited an earlier and more pronounced improvement in QoL, symptoms scale and endoscopic findings (nasal polyp score and the bilateral modified Lund-Kennedy) as early from week 16, which improvement persisted for 2 years. A greater mean improvement of 33.4 ± 6.5 (95% CI: 20.3-46.4; p < 0.001) points in sinonasal outcome test 22 (SNOT-22) was associated with ESS at week 16, against omalizumab effect (17.8 ± 7.6 [95% CI: 2.6-33.0]; p = 0.023). At year 2, an improvement in SNOT-22 of 62.6 ± 8.9 (95% CI: 48.4-84.1; p < 0.001) points was exclusively associated with omalizumab. Clinical evidence of the effect of omalizumab added to ESS treatment is provided in this study in the short- and long-term.


Socio-cultural and clinical determinants of symptomatology in obsessional neurosis.
Eighty-two obsessional neurotics were studied from a phenomenological viewpoint in order to unmask the clinical and socio-cultural determinants of symptom-choice in this disorder. The form of obsessions and compulsions seemed to be affected primarily by intrinsic factors (age, sex, I.Q.) while their content was affected equally, if not more, by extrinsic factors (religion, locality, social class). Patient's age at the onset of illness seemed to be an extremely relevant factor insofar as it affected both the form and the content of symptoms. Some socio-cultural explanations have been offered these findings. The data is important insofar as it provides a baseline for cross-cultural studies of the phenomenology of obsessional illness.


Pharmacologic treatment of hyperlipidemia reduces glomerular injury in rat 5/6 nephrectomy model of chronic renal failure.
The role of lipid abnormalities in the pathogenesis of focal glomerulosclerosis was investigated in the rat remnant kidney model of chronic renal failure. Rats subjected to right nephrectomy and two-thirds segmental infarction of the left kidney (5/6 nephrectomy) were treated for 10 weeks with the lipid-lowering agent clofibric acid. Both serum cholesterol and urine albumin excretion were significantly reduced by clofibric acid. At 10 weeks, the percent of glomeruli with focal glomerulosclerosis was 5 +/- 2% in clofibric acid-treated and 24 +/- 5% in untreated 5/6 nephrectomy rats (p less than 0.01). Inulin clearance was greater in clofibric acid-treated than in untreated 5/6 nephrectomy rats (0.28 +/- 0.02 versus 0.22 +/- 0.02 ml/min 100 g body wt, p less than 0.05). Body weight, kidney weight, and systemic blood pressure were not significantly altered by clofibric acid. Micropuncture studies, performed in separate groups of clofibric acid-treated and untreated 5/6 nephrectomy rats, demonstrated elevated single nephron glomerular filtration rates and glomerular capillary pressures 4 weeks after surgery. However, clofibric acid did not significantly alter single nephron glomerular filtration rates (95 +/- 2.1 nl/min in treated versus 97.0 +/- 6.2 nl/min in untreated, p greater than 0.05) or glomerular capillary pressures (56.6 +/- 1.5 mm Hg in treated versus 57.8 +/- 0.8 mm Hg in untreated, p greater than 0.05) in 5/6 nephrectomy rats. In a separate set of experiments, 5/6 nephrectomy rats were treated with the specific cholesterol synthesis inhibitor, mevinolin. Mevinolin improved serum lipid levels and reduced albuminuria in 5/6 nephrectomy rats without causing significant alterations in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)


Laparoendoscopic rendezvous versus preoperative ERCP and laparoscopic cholecystectomy for the management of cholecysto-choledocholithiasis: interim analysis of a controlled randomized trial.
Although the ideal management of cholecysto-choledocholi-thiasis is controversial, the 2-stage approach [endoscopic retrograde cholangiopancreatography (ERCP), sphincterotomy, and common bile duct (CBD) clearance followed by laparoscopic cholecystectomy] remains the standard way of management worldwide. One-stage approach using the so-called laparoendoscopic rendezvous (LERV) technique offers some advantages, mainly by reducing the hospital stay and the risk of post-ERCP pancreatitis. To compare the LERV 1-stage approach with the standard 2-stage approach consisting of preoperative ERCP followed by laparoscopic cholecystectomy for the treatment of cholecysto-choledocholithiasis. Controlled randomized trial, University/Teaching Hospital. : Patients with cholecysto-choledocholithiasis were randomized either to LERV or to the 2-stage approach. Both elective and emergency cases were included in the study. Primary endpoint was to detect difference in overall hospital stay, whereas secondary endpoints were (i) to detect differences in morbidity (especially post-ERCP pancreatitis) and (ii) success of CBD clearance. This is an interim analysis of the first 100 randomized patients. Hospital stay was significantly shorter in the LERV group; median 4 (2-19) days versus 5.5 (3-22) days, P = 0.0004. There was no difference in morbidity and success of CBD clearance between the 2 groups. Post-ERCP amylase value was found significantly lower in the LERV group: median 65 (16-1159) versus 91 (30-1846), P = 0.02. Interim analysis of the results suggests the superiority of the LERV technique in terms of hospital stay and post-ERCP hyperamylasemia.


Alterations of mental defeat and cognitive flexibility during cognitive behavioral therapy in patients with major depressive disorder: a single-arm pilot study.
Mental defeat affects the occurrence and chronicity of depression and cognitive flexibility. This study aimed to examine changes in mental defeat and cognitive flexibility scores after cognitive behavioral therapy including IR. In the intervention group, patients with depression (n = 18, mean age = 37.89 years) received 15 cognitive behavioral therapy sessions. Patients completed the Beck Depression Inventory-II; Mental Defeat Scale; Cognitive Flexibility Scale; EuroQol five dimensions questionnaire; Patient Health Questionnaire-9 and seven-item Generalized Anxiety Disorder Scale before the intervention, after six sessions, and post-intervention. The healthy control group (n = 33, mean age = 37.91) completed all scales once and did not receive treatment. Post-cognitive behavioral therapy, a significant decrease was observed in Beck Depression Inventory-II, Mental Defeat Scale, Cognitive Flexibility Scale, and Patient Health Questionnaire-9 scores. Although mental defeat and cognitive flexibility did not reach the level of the healthy control group, they demonstrated improvement. Therefore, when treating depression, mental defeat and cognitive flexibility should be measured in addition to depressive symptoms. Trial registration This study was registered retrospectively in the national UMIN Clinical Trials Registry on July 25, 2016 (registration ID: UMIN000023320).


Lead content in Spanish market infant formulas and toxicological contribution.
Lead content was investigated in infant formulas by using graphite furnace atomic absorption spectroscopy (GFAAS). Formulas were distinguished as 'beginner', 'continuation' and 'special infant formula', the latter being classified as subtypes 'hypoallergenic', 'without lactose', 'vegetable base' and 'others'. The mean concentrations of lead were 25.7+/-8.4, 36.9+/-6.4 and 43.5+/-16.3 microg kg(-1) for beginner, continuation and special infant formula, respectively. Two-factor (types and subtypes) variance analyses were made and Tukey's mean homogeneity test (p < 0.05) was also performed for the formation of homogeneous groups. Significant differences (p < 0.001) were observed between types and two homogeneous groups were formed by the special infant formula type, with the highest lead content; the other group was constituted by the beginner type; and included in both groups were the continuation type infant formula. Their contribution to the provisional weekly intake (PTWI) was calculated from the mean concentrations in each type of infant formula, showing them to be food with a low toxicological risk (< 30% PTWI).


Fatal paracetamol poisoning in an epileptic.
Treatment nomograms are used in paracetamol poisoning for indicating when antidotes should be given to prevent hepatic or renal damage. We report a fatal case of paracetamol poisoning in an epileptic taking phenytoin, in whom no antidotal treatment was given because it was not indicated.


Bis[μ-N-(diethyl-amino-κN)dimethyl-silylanilido-κN:N]bis-[chlorido-cobalt(II)].
In the title binuclear Co(II) complex, [Co(2)(C(12)H(21)N(2)Si)(2)Cl(2)], an inversion center is located at the mid-point between the two Co atoms in the dimeric mol-ecule. The bidentate N-silylated anilide ligand coordinates the Co(II) atom in an N,N'-chelating mode and provides the anilide N atom as a bridge to link two Co(II) atoms. The two ends of the N-Si-N chelating unit exhibit different affinities for the metal atom. The Co-N(anilide) bond is 2.031 (6) Å and Co-N(amino) bond is 2.214 (6) Å. The four-coordinate Co atom presents a distorted tetra-hedral geometry, while the dimeric aggregation exhibits a (CoN)(2) rhombus core with 1.998 (6) Å as the shortest sides and shows a ladder structure composed of Co, N and Si atoms.


Comparison of primary lung tumor incidences in the rat evaluated by the standard microscopy method and by multiple step sections.
The data presented in this paper have been derived from a carcinogenicity experiment with rats as part of a comprehensive research project focused on experimental studies on the toxicity and carcinogenicity of intratracheally instilled granular dusts [Ernst H, Rittinghausen S, Bartsch W, Creutzenberg O, Dasenbrock C, Görlitz B-D et al. Pulmonary inflammation in rats after intratracheal instillation of quartz, amorphous SiO(2), carbon black, and coal dust and the influence of poly-2-vinylpyridine-N-oxide (PVNO). Exp Toxicol Pathol 2002; 54: 109-26; Ernst H, Kolling A, Bellmann B, Rittinghausen S, Heinrich U, Pott F. Pathogenetische und immunbiologische Untersuchungen zur Frage: Ist die Extrapolation der Staubkanzerogenität von der Ratte auf den Menschen gerechtfertigt? Teil II: Histologie. Abschlussbericht. Umweltforschungsplan des Bundesministeriums für Umwelt, Naturschutz und Reaktorsicherheit. November 2005. http://www.umweltdaten.de/publikationen/fpdf-l/3033.pdf]. The results of the standard approach to histological sampling in rodent carcinogenicity inhalation studies were compared to those obtained after supplemental evaluation of step sections at intervals of 250microm through the entire lung. Seven lung tissue specimens (six sections) each of 251 rats (55 rats of the control group, 53 rats of the group treated with quartz DQ 12, 56 rats of the group treated with quartz DQ 12 and PVNO (poly-2-vinylpyridine-N-oxide), 53 rats of the group treated with amorphous SiO(2), and 17 rats each of the groups treated with coal dust and carbon black) were evaluated by light microscopy. At least 60 hematoxylin and eosin (H&E)-stained sections per lung were evaluated of 99 female rats (30 rats of the control group, 7 rats each of the groups treated with quartz, quartz and PVNO, and carbon black, 31 rats of the group treated with amorphous SiO(2), and 17 rats treated with coal dust). For the neoplastic and pre-neoplastic lesions detected in the serial slides an approximate value of the whole tumor volume was calculated. The detection of tumors with a diameter of 0.25mm was possible. Based on the size distribution of 75 tumor volumes, the probability of detecting a tumor was 86% when using 12 sections. The addition of step sections enhanced the tumor detection rate from 17 to a total number of 44 lung tumors in the quartz-treated rats, from 6 to 10 in the quartz- and PVNO-treated rats, from 4 to 11 in the amorphous SiO(2)-treated rats, and from 4 to 10 in the carbon black-treated rats. Both the tumor multiplicity and the number of rats with pre-neoplastic lesions increased. These additional data corroborated the initial findings in all experimental groups and provided statistically significant results confirming the equivocal evidence of carcinogenic activity of amorphous SiO(2) in female Wistar rats. This technique offered accurate information on the incidence, histological type, size, and location of proliferative lesions in the entire lung, but the benefit must be balanced against the extra financial effort.


Hospital Length of Stay and 30-Day Mortality Prediction in Stroke: A Machine Learning Analysis of 17,000 ICU Admissions in Brazil.
Hospital length of stay and mortality are associated with resource use and clinical severity, respectively, in patients admitted to the intensive care unit (ICU) with acute stroke. We proposed a structured data-driven methodology to develop length of stay and 30-day mortality prediction models in a large multicenter Brazilian ICU cohort. We analyzed data from 130 ICUs from 43 Brazilian hospitals. All consecutive adult patients admitted with stroke (ischemic or nontraumatic hemorrhagic) to the ICU from January 2011 to December 2020 were included. Demographic data, comorbidities, acute disease characteristics, organ support, and laboratory data were retrospectively analyzed by a data-driven methodology, which included seven different types of machine learning models applied to training and test sets of data. The best performing models, based on discrimination and calibration measures, are reported as the main results. Outcomes were hospital length of stay and 30-day in-hospital mortality. Of 17,115 ICU admissions for stroke, 16,592 adult patients (13,258 ischemic and 3334 hemorrhagic) were analyzed; 4298 (26%) patients had a prolonged hospital length of stay (> 14 days), and 30-day mortality was 8% (n = 1392). Prolonged hospital length of stay was best predicted by the random forests model (Brier score = 0.17, area under the curve = 0.73, positive predictive value = 0.61, negative predictive value = 0.78). Mortality prediction also yielded the best discrimination and calibration through random forests (Brier score = 0.05, area under the curve = 0.90, positive predictive value = 0.66, negative predictive value = 0.94). Among the 20 strongest contributor variables in both models were (1) premorbid conditions (e.g., functional impairment), (2) multiple organ dysfunction parameters (e.g., hypotension, mechanical ventilation), and (3) acute neurological aspects of stroke (e.g., Glasgow coma scale score on admission, stroke type). Hospital length of stay and 30-day mortality of patients admitted to the ICU with stroke were accurately predicted through machine learning methods, even in the absence of stroke-specific data, such as the National Institutes of Health Stroke Scale score or neuroimaging findings. The proposed methods using general intensive care databases may be used for resource use allocation planning and performance assessment of ICUs treating stroke. More detailed acute neurological and management data, as well as long-term functional outcomes, may improve the accuracy and applicability of future machine-learning-based prediction algorithms.


Adiponectin: protection of the endothelium.
Low levels of adiponectin, a fat-derived hormone, are found in coronary heart disease, type 2 diabetes, obesity, and other insulin-resistant states. Conversely, high adiponectin levels are predictive of reduced coronary risk in long-term epidemiologic studies. A close association between hypoadiponectinemia and endothelial dysfunction has also been demonstrated. The various mechanisms through which adiponectin may protect the endothelium, via its insulin-sensitizing, antiatherogenic, anti-inflammatory, and antioxidant properties, are reviewed.


Mechanistic insights into functional mitral regurgitation.
Effective valve repair in patients with mitral regurgitation (MR) demands an understanding of its mechanism. In patients with ischemic heart disease and functional MR, which doubles late mortality, normal leaflets are apically displaced. This reflects an altered balance of forces acting on the leaflets: increased tethering forces restricting closure, resulting from an altered geometry of leaflet attachments, and decreased ventricular forces acting to close the leaflets. Extensive evidence confirms a central and predominant role of tethering as the final common pathway inducing functional MR; left ventricular (LV) pressure dynamically modulates the orifice area. Because ischemic MR is a disease of the entire mitral complex, including the remodeling LV, reducing annular size alone is often ineffective. Undersizing rings attempts to compensate for tethering; new and potentially more effective strategies directly address tethering by infarct plication, papillary muscle repositioning with a localized patch, or basal chordal cutting to increase coaptational surface area without prolapse. A comprehensive understanding of the valve in its ventricular context, therefore, provides new opportunities for successful valve repair in patients.


Socioeconomic status and modification of atherosclerotic cardiovascular disease risk prediction: epidemiological analysis using data from the atherosclerosis risk in communities study.
Examine whether the relationship between the pooled cohort equations (PCE) predicted 10-year risk for atherosclerotic cardiovascular disease (ASCVD) and absolute risk for ASCVD is modified by socioeconomic status (SES). Population-based longitudinal cohort study-Atherosclerosis Risk in Communities (ARIC)-investigating the development of cardiovascular disease across demographic subgroups. Four communities in the USA-Forsyth County, North Carolina, Jackson, Mississippi, suburbs of Minneapolis, Minnesota and Washington County, Maryland. We identified 9782 ARIC men and women aged 54-73 without ASCVD at study visit 4 (1996-1998). Risk ratio (RR) differences in 10-year incident hospitalisations or death for ASCVD by SES and PCE predicted 10-year ASCVD risk categories to assess for risk modification. SES measures included educational attainment and census-tract neighbourhood deprivation using the Area Deprivation Index. PCE risk categories were 0%-5%, >5%-10%, >10%-15% and >15%. SES as a prognostic factor to estimate ASCVD absolute risk categories was further investigated as an interaction term with the PCE. ASCVD RRs for participants without a high school education (referent college educated) increased at higher PCE estimated risk categories and was consistently >1. Results indicate education is both a risk modifier and delineates populations at higher ASCVD risk independent of PCE. Neighbourhood deprivation did modify association but was less consistent in direction of effect. However, for participants residing in the most deprived neighbourhoods (referent least deprived neighbourhoods) with a PCE estimated risk >10%-15%, risk was significantly elevated (RR 1.65, 95% CI 1.05 to 2.59). Education and neighbourhood deprivation inclusion as an interaction term on the PCE risk score was statistically significant (likelihood ratio p≤0.0001). SES modifies the association between PCE estimated risk and absolute risk of ASCVD. SES added into ASCVD risk prediction models as an interaction term may improve our ability to predict absolute ASCVD risk among socially disadvantaged populations.


The effect of amorphous calcium carbonate as a culture media supplement on embryonic development of murine sibling embryos.
The aim of this study was to compare the addition in culture media of stabilized amorphous calcium carbonate (ACC) versus calcium chloride (CaCl2) or calcium carbonate in crystalline form (CCC) on growth rates among sibling mouse embryos. We evaluated the effect of different ACC concentrations on the rates of embryo compaction at 60 h, blastocyst rate at 84 h and percentage of fully hatched at 108 h following hCG injection. As ACC is stabilized by tripolyphosphate (TPP), we also evaluated the addition of TPP alone to the culture media. Finally, we compared supplemented ACC culture media to one-step SAGE and Irvine cleavage media. The results revealed that ACC accelerates the compaction and blastocyst rates, as well as the percentage of fully hatched embryos in a dose-dependent manner, with an increased positive effect at 2.5 mM. The magnitude of the effect for ACC-supplemented media on the embryo developmental rate was between 30 to 40% (p < 0.01) faster for each stage, compared to both SAGE and Irvine one-step standard media. Embryos cultured with SAGE or Irvine media with or without supplementation of CaCl2 or CCC, did not produce the same improvements as observed with ACC. In conclusion, the ACC demonstrates a rapid modulation effect for restoring media optimal pH. ACC can inhibit cathepsin B activity during in vitro culture of fibroblast cells. The beneficial impact of ACC on cleavage mouse embryos is likely due to an improved buffering effect causing slower pH media variations, which may enhance quality and implantation potential of embryos following in vitro culture.


Biomass to hydrogen-rich syngas via catalytic steam gasification of bio-oil/biochar slurry.
The catalytic steam gasification of bio-oil/biochar slurry (bioslurry) for hydrogen-rich syngas production was investigated in a fixed-bed reactor using LaXFeO3 (X=Ce, Mg, K) perovskite-type catalysts. The effects of elemental substitution in LaFeO3, temperature, water to carbon molar ratio (WCMR) and bioslurry weight hourly space velocity (WbHSV) were examined. The results showed that La0.8Ce0.2FeO3 gave the best performance among the prepared catalysts and had better catalytic activity and stability than the commercial 14 wt.% Ni/Al2O3. The deactivation caused by carbon deposition and sintering was significantly depressed in the case of La0.8Ce0.2FeO3 catalyst. Both higher temperature and lower WbHSV contributed to more H2 yield. The optimal WCMR was found to be 2, and excessive introducing of steam reduced hydrogen yield. The La0.8Ce0.2FeO3 catalyst gave a maximum H2 yield of 82.01% with carbon conversion of 65.57% under the optimum operating conditions (temperature=800°C, WCMR=2 and WbHSV=15.36h(-1)).


Dissipation of six fungicides in greenhouse-grown tomatoes with processing and health risk.
Greenhouse studies were conducted to evaluate the dissipation rate kinetics and estimate the behavior of selected pesticides after washing, peeling, simmering, and canning of tomato expressed as processing factor (PF). Two varieties (Marissa and Harzfeuer) were treated by six fungicides: azoxystrobin, boscalid, chlorothalonil, cyprodinil, fludioxonil, and pyraclostrobin at single and double dose and risk assessment defined as hazard quotient was performed. The QuEChERS method was used for sample preparation followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The dissipation of fungicides approximately fitted to a first-order kinetic model, with half-life values ranging from 2.49 and 2.67 days (cyprodinil) to 5.00 and 5.32 days (chlorothalonil) for Marissa and Harzfeuer variety, respectively. Results from processing studies showed that treatments have significant effects on the removal of the studied fungicides for both varieties. The PFs were generally less than 1 (between 0.01 and 0.90) and did not depend on variety. The dietary exposure assessed based on initial deposits of application at single and double dose on tomatoes and concentration after each process with PF correction showed no concern to consumer health. Our results would be a useful tool for monitoring of fungicides in tomatoes and provide more understanding of residue behavior and risk posed by these fungicides.


A missense mutation in the coding region of the toll-like receptor 4 gene affects milk traits in Barki sheep.
Milk production is one of the most desirable traits in livestock. Recently, the toll-like receptor (TLR) has been identified as a candidate gene for milk traits in cows. So far, there is no information concerning the contribution of this gene in milk traits in sheep. This study was designed to investigate the TLR 4 gene polymorphisms in Barki ewes in Egypt and then correlate that with milk traits in order to identify potential single nucleotide polymorphisms (SNPs) for these traits in sheep. A part of the ovine TLR 4 gene was amplified in Barki ewes, to identify the SNPs. Consequently; Barki ewes were genotyped using polymerase chain reaction-single strand conformation polymorphism protocol. These genotypes were correlated with milk traits, which were the daily milk yield (DMY), protein percentage (PP), fat percentage (FP), lactose percentage, and total solid percentage (TSP). Age and parity of the ewe had a significant effect (p<0.05 or p<0.01) on DMY, FP, and TSP. The direct sequencing identified a missense mutation located in the coding sequence of the gene (rs592076818; c.1710C>A) and was predicted to change the amino acid sequence of the resulted protein (p.Asn570Lys). The association analyses suggested a significant effect (p<0.05) of the TLR genotype on the FP and PP, while the DMY tended to be influenced as well (p = 0.07). Interestingly, the presence of the G allele tended to increase the DMY (+40.5 g/d) and significantly (p<0.05 or p<0.01) decreased the FP (-1.11%), PP (-1.21%), and TSP (-7.98%). The results of this study suggested the toll-like receptor 4 (TLR4) as a candidate gene to improve milk traits in sheep worldwide, which will enhance the ability to understand the genetic architecture of genes underlying SNPs that affect such traits.


The effects of nitric oxide donors on the sporulation of Eimeria tenella oocysts.
Nitric oxide (NO) is involved in many physiological processes including regulation of blood pressure, immune response, and neural communication. The effects of NO donors on the sporogony of Eimeria tenella oocysts and the blocking effects of NO scavenger, hemoglobin (Hb), against NO donors were investigated in this study. The results showed that the sporulation of oocysts could be completely inhibited by acidic sodium nitrite (NaNO2), S-nitroso-glutathione (GSNO) or S-nitroso-N-acetyl-dl-penicillamine (SNAP) in profound dose-dependent and time-dependent manners, and the inhibiting process was irreversible and not affected by feces of chickens. However, not all NO donors in this study, such as sodium nitroprusside (SNP), demonstrated above-mentioned effect. The NO scavenger Hb could significantly prevent the detrimental effects of NO donors on the sporogony of oocysts in a dose-dependent manner. At present, the inhibiting mechanism of NO donors on the sporulation of oocysts was still unclear.


Is there a role of pulmonary rehabilitation in extrapulmonary diseases frequently encountered in the practice of physical medicine and rehabilitation?
There is a group of diseases such as low back pain, osteoporosis, fibromyalgia and obesity for which pulmonary rehabilitation can be applied. Although these diseases do not directly impact the lungs, respiratory dysfunction occurs through various mechanisms during the disease process and complicates the underlying primary disease. Respiratory dysfunction and spirometric abnormalities have been observed from the early stages of these diseases, even without obvious signs and symptoms. These patients should be carefully evaluated for pulmonary problems as a sedentary lifestyle may hide the presence of respiratory symptoms. Once pulmonary problems have been detected, pulmonary rehabilitation should be added to the routine treatment of the primary disease.


Metal-activated C-peptide facilitates glucose clearance and the release of a nitric oxide stimulus via the GLUT1 transporter.
Proinsulin C-peptide has been implicated in reducing complications associated with diabetes and also in improving blood flow. We hypothesised that incubation of erythrocytes with C-peptide would improve the ability of these cells to release ATP, a stimulus for nitric oxide production. Erythrocytes obtained from rabbits (n = 11) and both healthy and type 2 diabetic humans (n = 7) were incubated with C-peptide in the absence and presence of Fe2+ and Cr3+, and the resulting ATP release was measured via chemiluminescence. This release was also measured in the presence and absence of phloretin, an inhibitor of GLUT1, and also of mannose, a glycolysis inhibitor. To determine glucose transport, 14C-labelled glucose was added to erythrocytes in the presence and absence of the C-peptide-metal complex and the aforementioned inhibitors. The release of ATP from the erythrocytes of patients with diabetes increased from 64 +/- 13 to 260 +/- 39 nmol/l upon incubation of the cells in C-peptide. The C-peptide activity was dependent upon binding to Fe2+, which was extended upon binding to Cr3+. The increase in ATP release from the erythrocytes is due to metal-activated C-peptide stimulation of glucose transfer into the erythrocytes via the GLUT1 transporter. In the presence of C-peptide complexed to Cr3+, the amount of glucose transferred into the erythrocyte increased by 31%. When complexed to Fe2+ or Cr3+, C-peptide has the ability to promote ATP release from erythrocytes. This release is due to an increase in glucose transport through GLUT1.


Critical aspects on traditional antivenom production processes and their optimization by factorial analysis.
Most antivenoms are produced by techniques developed over 50 years ago, with minor modifications. Herein we revise the core of traditional antivenom production processes aiming to optimize key determinants for both consistent antivenom production and the best balance between F(ab')2 quality and recovery. Factorial design analysis revealed that pepsin digestion of 1:3 saline diluted equine plasma for 60 min under pH: 3.20, 37 °C temperature and a 1:15 pepsin to protein ratio conditions, allowed to achieve maximal IgG to F(ab')2 conversion with minimal protein aggregate formation. Further downstream processing by salting out with ammonium sulfate was also studied by factorial analysis. The influence of ammonium sulfate (AS) concentration, temperature (T) and the albumin to total plasma protein ratio plasma (Alb:P) were assayed, revealing that both AS, T and their interaction have a significant impact in F(ab')2 quality and recovery. Taking into account the existing compromise between F(ab')2 monomer recovery and quality two alternative conditions were selected: 14 g/dl AS at 56 °C and, alternatively 16 g/dl AS at 30 °C. Reasonable yields (42%) and product quality (2.5% of aggregates) without significant changes in production cost of traditional methodologies was achieved under the optimized conditions found.


Autogenous transplantation of maxillary and mandibular molars.
Autogenous tooth transplantation has been used as a predictable surgical approach to correct malocclusion and replace edentulous areas. This article focuses on the surgical approach and technique for molar transplantation. Thirty-two patients aged between 11 and 25 years underwent 44 autogenous molar transplantations. The procedure involved transplantation of impacted or newly erupted third molars into the extraction sockets of nonrestorable molars and surgical removal and replacement of horizontally impacted molars into their proper vertical alignment. Five basic procedural concepts were applied: 1) atraumatic extraction, avoiding disruption of the root sheath and root buds; 2) apical contouring of bone at the transplantation site and maxillary sinus lift via the Summers osteotome technique, when indicated, for maxillary molars; 3) preparation of a 4-wall bony socket; 4) avoidance of premature occlusal interferences; and 5) stabilization of the tooth with placement of a basket suture. All 32 patients successfully underwent the planned procedure. To date, 2 patients have had localized infection that resulted in loss of the transplant. The remaining 42 transplants remain asymptomatic and functioning, with a mean follow-up period of 19 months. No infection, ankylosis, loss of the transplant, or root resorption has been noted. In addition, endodontic therapy has not been necessary on any transplanted teeth. Autogenous tooth transplantation has been discussed and described in the literature previously, with a primary focus on cuspid and bicuspid transplantation. The molar transplant is infrequently discussed in today's literature, possibly because of the preponderance of titanium dental implants. Autogenous molar transplantation is a viable procedure with low morbidity and excellent functional and esthetic outcomes. This report shows the successful transplantation of 42 of 44 molars in 32 patients with a mean follow-up period of 19 months.


Reducing toxicity and antimicrobial activity of a pesticide mixture via photo-Fenton in different aqueous matrices using iron complexes.
This is the first study to investigate ethylenediamine-N,N'-disuccinic acid (EDDS)/photo-Fenton process to polish real wastewater containing pesticides for possible water reuse. To this end, simultaneous degradation of pesticides ametrine, atrazine, imidacloprid and tebuthiuron was evaluated in distilled water (DW) and in sewage treatment plant (STP) effluent at initial pH 6.0. Several operational parameters (Fe3+-EDDS concentration, Fe3+-EDDS molar ratio, EDDS addition patterns and radiation source) were evaluated. 80-98% removal of target pesticides were obtained in DW using 30 μmol L-1 of Fe3+-EDDS with a molar ratio of 1:2 (300 μmol L-1 of H2O2). In addition, the proposed Fe3+-EDDS photo-Fenton at pH 6 was more efficient than classic photo-Fenton at pH 2.7 (30-84% removal). Experiments conducted in the presence of radical trapping agents (2-propanol or chloroform) revealed that HO• was the most active radical during treatment. Matrix composition strongly affected the degradation of target pesticides as a six-fold higher concentration of reagents (180 μmol L-1 of Fe3+-EDDS and 1800 μmol L-1 of H2O2) was needed to reach the same efficiency in STP compared to DW. Even so, first order rate constants corresponding to the degradation of pesticides in DW (k = 0.098-0.85 min-1) were nearly two-fold higher than in STP (k = 0.079-0.49 min-1) under the same radiation source (black-light or solar radiation). Finally, acute toxicity towards Vibrio fischeri and Drosophila melanogaster flies, and antibacterial activity assessed for Escherichia coli were eliminated after the application of the proposed treatment, thus indicating environmental safety for either discharge or reuse of treated wastewater for crop irrigation in agriculture.


Systematic neuronal and muscle induction systems in bone marrow stromal cells: the potential for tissue reconstruction in neurodegenerative and muscle degenerative diseases.
Because bone marrow stromal cells (MSCs) are easily accessible from both healthy donors and patients and can be expanded on a therapeutic scale, they have attracted attention for cell-based therapy. Benefits of MSCs have been discussed mainly from two aspects: one is their tissue protective and immunomodulatory effects, and the other is their capability under specific manipulations to differentiate into various cell types. In this review, their differentiation into functional neural and muscle cell lineages is the focus, and their potential to the application for tissue reconstruction in neurodegenerative and muscle degenerative diseases is discussed.


Changes in overactive bladder medication following bariatric surgery: segmented regression analysis.
Bariatric surgery has shown reductions in overactive bladder (OAB) symptoms; however, the impacts on OAB treatment is unknown. The goal of our study is to evaluate the impact of bariatric surgery on OAB medication utilization. We used IBM® MarketScan® commercial databases from 2005 to 2018. We included patients aged ≥ 18 years with 360 days of continuous enrollment before and after bariatric surgery (Roux-en-Y Gastric Bypass and Sleeve Gastrectomy) with at least one fill of an OAB medication in the 360 days prior to bariatric surgery. We evaluated all included patients and stratified by surgery type and patient sex. Segmented regression analyses were used to assess the proportion of patients on OAB medications before and after bariatric surgery. We replicated our findings using hip or knee replacement surgery as a negative control. Among the included patients (n = 3069), 92.2% were females, 58.6% underwent Roux-en-Y Gastric Bypass. Immediately following bariatric surgery, the proportion of patients treated with an OAB medication reduced from 34.8 to 14.1% (p < 0.001) resulting in a 59.5% relative reduction. Patients who underwent Roux-en-Y Gastric Bypass vs. Sleeve Gastrectomy (63.8% vs. 55.1%) relative reduction (p = 0.009)) and females versus males [62.3% vs. 52.9% relative reduction (p < 0.001)] had a more pronounced reduction in OAB medication use. There was slight decrease in OAB medication use in the negative control analysis. A reduction in OAB medication use following bariatric surgery may be associated with a reduction in OAB symptoms suggesting an additional benefit of bariatric surgery.


Enhanced Recovery after Surgery in Elderly Gastric Cancer Patients Undergoing Laparoscopic Total Gastrectomy.
The aim of this study was to evaluate the effects of the enhanced recovery after surgery (ERAS) program versus conventional perioperative care on the short-term postoperative outcomes among elderly patients with gastric cancer who are undergoing laparoscopic total gastrectomy. Elderly patients with gastric cancer (age ≥ 65 y) who are undergoing laparoscopic total gastrectomy were randomized to ERAS or conventional perioperative care groups. Short-term postoperative outcomes, including postoperative hospital stay, mortality, complications, readmission rate, and reoperation rate were compared between the two groups. In addition, blood samples were taken preoperatively (baseline) and on postoperative days 1, 3, and 5. Systemic human leukocyte antigen (HLA)-DR expression on monocytes and C-reactive protein (CRP) were analyzed. Of the 171 eligible patients, 85 patients were assigned to receive ERAS program treatment (ERAS group) and 86 patients to receive conventional care (conventional group). The patients' characteristics were comparable. Postoperative hospital stay was shorter in the ERAS group than in the conventional group (11 [7-11] versus 13 [8-20] d, P < 0.001). Hospital mortality, overall morbidity, morbidity ≥ Clavien-Dindo (C-D) grade II, readmission rate, and reoperation rate did not show significant differences between the two groups. However, morbidity ≥ C-D grade IIIa was lower in the ERAS group than that in the conventional group (8.2% versus 18.6%, P = 0.047). The ERAS program shortened the number of days to postoperative first flatus, first defecation, semifluid diet, and soft bland diet. Moreover, the ERAS program increased the HLA-DR expression on monocytes and decreased the CRP levels on postoperative days 1, 3, and 5. The ERAS program was feasible and effective for elderly patients with gastric cancer who are undergoing laparoscopic total gastrectomy. The benefits of ERAS were associated with improvement of impaired immune function and suppression of inflammatory reaction.


Accessibility changes across the mouse Igh-V locus during B cell development.
During their development, B and T lymphocytes are thought to undergo several cycles of chromatin remodeling at their antigen receptor loci that serve to regulate access of a common V(D)J recombinase to particular gene segments. We used germ-line transcription and susceptibility to DNasel as markers to examine tissue and stage-specific changes in chromatin structure surrounding genes of the VHJ558, VH10, and VHS107 families, whose members are located at discreet subregions of the locus. Germ-line VH transcripts from all three families were detectable at pro- and pre-B cell stages. Transcripts from the VH10 and VHS107 families, but not VHJ558, remained detectable at the immature and mature B cell stages. Unexpectedly, none of the germ-line VH loci examined were markedly nuclease sensitive, regardless of cell type or transcriptional activity. A modest degree of nuclease sensitivity was noted at the VHJ558 loci of pro-B and pre-B cells, however. Our data suggest that the entire Igh-V locus becomes accessible at early B cell stages, and returns thereafter to an inaccessible state. However, the timing of these accessibility changes does not occur uniformly across the VH array. These results imply that multiple long-range elements are involved in targeting VH genes for rearrangement.