Influence of hydroxystearic acid on in vitro cell proliferation.
Lipid peroxidation products have recently been proposed among the possible regulators of tumour cell growth. According to our current working hypothesis, the greatly diminished content of such products in tumour cells might relieve the inhibition of cell growth thus leading to uncontrolled proliferation. Hydroperoxy- and hydroxy derivatives of long chain fatty acids have been identified and determined in normal and tumour cells. Among these, hydroxystearic acid (HSA) has been shown to have a different cytostatic and cytotoxic effect when administered to murine lung carcinoma cells or to human colon tumour cells. It interferes with cell cycle kinetics, blocking the murine cells in G2-M and the human ones in G0-G1. The molecular target of HSA in both cell lines has been shown to be the cdc2 kinase complex. The results so far obtained in tumour as long as in normal highly proliferating cells do not exclude a potential future use of this class of compounds as selective anti tumour drugs.


Identification of Fusarium species isolated from stored apple fruit in Croatia.
Several species of the genus Fusarium can cause apple fruit to rot while stored. Since Fusarium taxonomy is very complex and has constantly been revised and updated over the last years, the aim of this study was to identify Fusarium species from rotten apples, based on combined morphological characteristics and molecular data. We identified 32 Fusarium isolates from rotten apple fruit of cultivars Golden Delicious, Jonagold, Idared, and Pink Lady, stored in Ultra Low Oxygen (ULO) conditions. Fusarium rot was detected in 9.4 % to 33.2 % of naturally infected apples, depending on the cultivar. The symptoms were similar in all four cultivars: a soft circular brown necrosis of different extent, with or without visible sporulation. Fusarium species were identified by the morphology of cultures grown on potato-dextrose agar (PDA) and carnation leaf agar (CLA). Twenty one isolates were identified as Fusarium avenaceum and confirmed as such with polymerase chain reaction (PCR) using specific primer pair FA-ITSF and FA-ITSR. F. pseudograminearum,F. semitectum, F. crookwellense, and F. compactum were identified by morphological characteristics. F.avenaceum can produce several mycotoxins and its dominance in Fusarium rot points to the risk of mycotoxin contamination of apple fruit juices and other products for human consumption. Pathogenicity tests showed typical symptoms of Fusarium rot in most of the inoculated wounded apple fruits. In this respect Fusarium avenaceum, as the dominant cause of Fusarium rot in stored apple fruits is a typical wound parasite.


Resilience, Moral Distress, and Workplace Engagement in Emergency Department Nurses.
This cross-sectional, correlational study's purpose was to evaluate the effects of resilience and moral distress on workplace engagement in emergency department nurses providing direct patient care. Data were collected from 175 emergency department nurses using a Web-based survey. The higher the nurses' resilience and the lower their moral distress, the greater their workplace engagement. Resilience and moral distress were not correlated; furthermore, moral distress did not mediate a relationship between resilience and workplace engagement. Resilience was higher with greater job satisfaction, increased age, and longer tenure as a nurse. Workplace engagement increased with higher job satisfaction and less time seeking other employment. Moral distress scores were higher in nurses reporting lower job satisfaction. Multiple regression analysis revealed that resilience, job satisfaction, and moral distress were independent predictors of workplace engagement. Interventions that improve resilience and job satisfaction and/or lower moral distress may improve workplace engagement of emergency department nurses.


Decamethonium is a partial agonist at the nicotinic acetylcholine receptor.
The efficacy of decamethonium as an agonist at the nicotinic acetylcholine receptor has never been determined. Here, we demonstrate how patch clamp recording during rapid perfusion of agonists to outside-out patches from BC3H-1 cells can be used to provide an unambiguous estimate of the efficacy of decamethonium. First, we obtain the decamethonium concentration-response relationship between 10 and 1,000 microM decamethonium. The maximum channel open probability is small (< 0.02) and occurs at about 100 microM. This suggests two alternative explanations: decamethonium is a poor agonist or decamethonium is an efficacious agonist but a potent channel blocker. To distinguish between these alternatives, we perfuse mixtures of decamethonium and acetylcholine to generate acetylcholine concentration-response curves in the presence of 30, 100, and 1,000 microM decamethonium. We use a model for activation and block of the acetylcholine receptor by both agonists to fit these data and determine the binding affinity, efficacy, and blocking affinity of decamethonium. We conclude that the efficacy of decamethonium is low, 0.016. Decamethonium is a true partial agonist.


The use of the rare UUA codon to define "expression space" for genes involved in secondary metabolism, development and environmental adaptation in streptomyces.
In Streptomyces coelicolor, bldA encodes the only tRNA for a rare leucine codon, UUA. This tRNA is unnecessary for growth, but is required for some aspects of secondary metabolism and morphological development, as revealed by the phenotypes of bldA mutants in diverse streptomycetes. This article is a comprehensive review of out understanding of this unusual situation. Based on information from four sequenced genomes it now appears that, typically, about 2 approximately 3% of genes in any one streptomycete contain a TTA codon, most having been acquired through species-specific horizontal gene transfer. Among the few widely conserved TTA-containing genes, mutations in just one, the pleiotropic regulatory gene adpA, give an obvious phenotype: such mutants are defective in aerial growth and sporulation, but vary in the extent of their impairment in secondary metabolism in different streptomycetes. The TTA codon in adpA is largely responsible for the morphological phenotype of a bldA mutant of S. coelicolor. AdpA-dependent targets include several genes involved in the integrated action of extracellular proteases that, at least in some species, are involved in the conversion of primary biomass into spores. The effects of bldA mutations on secondary metabolism are mostly attributable to the presence of TTA codons in pathway-specific genes, particularly in transcriptional activator genes. This is not confined to S. coelicolor-it is true for about half of all known antibiotic biosynthetic gene sets from streptomycetes. Combined microarray and proteomic analysis of liquid (and therefore non-sporulating) S. coelicolor bldA mutant cultures revealed effects of the mutation during rapid growth, during transition phase, and in stationary phase. Some of these effects may be secondary consequences of changes in the pattern of ppGpp accumulation. It is argued that the preferential accumulation of the bldA tRNA under conditions in which growth is significantly constrained has evolved to favour the expression of genes that confer adaptive benefits in intermittently encountered sub-optimal environments. The evolution of this system may have been a secondary consequence of the selective pressure exerted by bacteriophage attack. Some biotechnological implications of bldA phenomenology are considered.


Borrelia arthritis in Sweden.
Antibodies to Borrelia spirochetes were determined by an enzyme-linked immunosorbent assay (ELISA) in sera from 298 patients with postinfectious arthritis. Sera from healthy individuals, patients with acute infectious meningitis of proven etiology and patients with multiple sclerosis served as controls. Titers above the 100% percentile of controls were found in five of 298 (2%) arthritis patients. Two of the arthritis patients had higher titers than any titers previously found in Swedish patients with Borrelia meningitis. It is concluded that a Borrelia etiology should be considered in patients with reactive or postinfectious arthritis of unknown origin.


The associations between spiritual well-being, hope and psychological symptoms in Chinese childhood cancer patients: A path analysis.
We aimed to test a model in which hope and spiritual well-being acted as protective factors against anxiety and depressive symptoms in childhood cancer patients (CCPs). We hypothesized that hope and spiritual well-being were mutually reinforcing factors that would both reduce anxiety and depressive symptoms. Using path analysis, the hypothetical model was tested on a cross-sectional sample of 412 Chinese CCPs aged 8-17 years. Self-reported measures were used to obtain data on participants' social and clinical characteristics, spiritual well-being, hope, anxiety and depressive symptoms. The hypothetical model was supported. Results suggested that sex, treatment type and diagnosis predicted spiritual well-being; diagnosis and time since diagnosis predicted hope. Spiritual well-being and hope were mutually predictive and mutually reinforcing, and were both negatively associated with anxiety and depressive symptoms. This model predicted 40% of the variance in spiritual well-being, 37% in hope, 39% in depressive symptoms, and 28% in anxiety. Spiritual well-being and hope were mutually reinforcing and served as protective factors against anxiety and depressive symptoms. These support the value for integrating spiritual and hope elements in developing interventions for CCPs to improve their spiritual and psychological well-being along the disease trajectory.


Mycophenolate in scleroderma-associated interstitial lung disease: Real-world data from rheumatology and pulmonology clinics in South Asia.
There is a paucity of real-world data on mycophenolate mofetil/mycophenolate sodium in systemic sclerosis-related interstitial lung disease. To study the efficacy of mycophenolate mofetil/ mycophenolate sodium in systemic sclerosis-related interstitial lung disease. In this single-centre study, clinical, laboratory and imaging details of consecutive patients with systemic sclerosis-related interstitial lung disease receiving mycophenolate mofetil/mycophenolate sodium from rheumatology and pulmonology clinics between January 2008 and March 2017 were retrospectively retrieved. The change in percentage of predicted normal forced vital capacity at last follow-up visit as compared with baseline was studied. In addition, high-resolution computed tomography scans at baseline and 2-year follow-up visit were scored as either stable/improved or worsened by experienced thoracic radiologists blinded to the clinical details of patients. Altogether, 88 patients (85.2% females) with mean age (SD) of 33.8 years (± 11.3) and median (interquartile range) duration of disease since non-Raynaud's symptoms of 36 months (13.5-60) were studied. Diffuse systemic sclerosis comprised 85.2% of them. The mean baseline forced vital capacity was 61.2 ± 17.9% and median scores for ground glass opacities and fibrosis in high-resolution computed tomography were 0.5 (0-1.3) and 1 (0-1.3), respectively. At a median follow-up duration of 30 months (interquartile range = 16.5-49), the percentage of forced vital capacity improved by 1.8% (-3.82 to 9.07) as compared with baseline visit (p = 0.02). In the 2-year follow-up, the ground glass opacity and fibrosis scores in high-resolution computed tomography improved in 17.3% and 7.7% of patients and stabilized in 63.5% and 78.8% patients, respectively. Mycophenolate mofetil/mycophenolate sodium was efficacious in improving /stabilizing forced vital capacity irrespective of the baseline high-resolution computed tomography lung scores in our patients with systemic sclerosis-related interstitial lung disease during the ⩾ 2-year follow-up period.


Neuroendocrine tumors of the gastrointestinal tract.
Neoplastic proliferations of neuroendocrine cells (NE) may occur throughout the entire GI tract but affect particularly appendix and ileum ("midgut carcinoids"), rectum ("hindgut carcinoids"), as well as stomach and the duodenum ("foregut carcinoids"). Only more exceptionally, they arise in the esophagus, jejunum and colon. The NE tumors encompass a heterogeneous gross and microscopic structural spectrum, ranging from inconspicuous microproliferations ("mucous membrane nevi") to bulky tumor masses. Their growth patterns are usually characteristic and easily recognized. In doubtful cases their NE differentiation becomes established by a characteristic silver affinity, by the ultrastructurally observed presence of characteristic "endocrine" secretion granules, and by immunohistochemically detectable occurrence of "pan-NE markers" (neuron-specific enolase, chromogranins, and synaptophysin), biogenic amines (mainly serotonin), and neurohormonal peptides. Foregut carcinoids usually contain serotonin, gastrin, and somatostatin, midgut carcinoids often only serotonin and tachykinins, whereas the hindgut carcinoids as a rule are multihormonal with a wide spectrum of hormonal peptides, including even insulin. Most GI NE tumors are found in the appendix (50%) and the ileum (30%). Practically all (98%) of the appendiceal NE tumors are benign. They have recently been proposed as arising from apparently Schwann-cell-related NE cells in the submucosa, whereas the ileal--and probably also all the other non-appendiceal NE tumors--are derived from the totipotential cells in epithelial crypts of the mucosa. Among the ileal NE neoplasms a large number can metastasize and result in a fatal outcome. The ability to metastasize is related to the size and to the multiplicity of the primary tumors at the time of initial diagnosis and, to some extent, to their histopathologic growth pattern. Now, some relationship between the prognosis and the cytochemically assessed nuclear DNA content of the NE tumor cells has also been established; not less than about 1/4 to 1/3 seem to be aneuploid. Almost 90% of the rectal carcinoids are benign. Exceptionally, a highly malignant NE neoplasms can arise from the colon/rectum--as well as from the esophagus--composed of NE cells of small and intermediate size. The NE tumors of the stomach are often composed of ECL (enterochromaffin-cell-like) cells; such ECL cell carcinoids are related to atrophic gastritis with pernicious anemia; experimentally, they can be induced by hypergastrinemia in rats. Duodenal carcinoids often contain psammoma bodies and can be associated with neurofibromatosis.


Growth and differentiation factors for B and T cells.
Many of the soluble factors controlling growth and differentiation of hematopoietic cells have recently become available as pure and recombinant proteins. This had led to a better understanding of where in the pathway of maturation and how these molecules act, as well as to the identification of specific receptors. As most readers of scientific literature have experienced, the extensive amount of data currently being published on this subject can lead to a great deal of confusion--especially for those scientists not directly involved in the field. Although new data is constantly being generated and future research will further elucidate the complexity of the role of signal molecules for hematopoietic cells, this short article is an attempt to give a simplistic overview of the present status.


Host specificity among Maculinea butterflies in Myrmica ant nests.
Ecological studies have been made of all 5 European species of Maculinea. These confirm that M. nausithous and M. rebeli live underground in Myrmica ant nests for 10 months of the year, as has long been known for the other 3 species. The main discovery was that each Maculinea species depends on a single, and different, host species of Myrmica. This specificity contradicts previous papers and scientific reviews of the relationship between Maculinea and ants. Therefore, early records are re-examined and 3 reasons are given to explain why most are misleading when applied to wild populations. Dependence on a single, rather than any, species of Myrmica explains why Maculinea populations exist in only a small minority of biotopes where their foodplants and Myrmica ants abound. It also explains the puzzling disappearance of Maculinea populations from apparently suitable sites. The discovery that M. alcon and M. rebeli depend on separate species of Myrmica that are not even closely related strengthens the argument that these butterflies are good species.


Adolescent pregnancy in Africa: a programmatic focus.
An increasing age of marriage coupled with high rates of premarital sexual activity have caused notable changes in the incidence of out-of-wedlock pregnancies in much of the developing world. In Africa, local policy makers are beginning to perceive the medical implications of these changes as the youth component of illicit abortion, maternal mortality, and sexually transmitted disease becomes more visible. Other social issues, which include school leaving, unemployment, violence and drug abuse, are emerging among the young people of Africa as elsewhere. A successful approach to these problems will require a multi-disciplinary perspective of the adolescent with professional contributions from the arenas of health, behavior, education and sociology. This report stresses the thesis that adolescents constitute a unique sub-population whose special needs must be recognized in Africa; strong institutional facilities are required, backed by committed advocates and leadership for the youth sector. Programs initiated in Kenya and Zimbabwe serve as useful models for other African locales.


Location by paper chromatography of compensatory ovarian hypertrophy (COH) inhibiting activity in isobutanol extracts of bovine pineals.
Bovine pineal glands were extracted according to the methods reported by Bensinger et al. (1973) and Cheesman and Fariss (1970). Isobutanol soluble COH-inhibiting activity was further separated by chromatography on Sephadex G-15 and paper chromatography. With the Bensinger method, different active pineal fractions were obtained from Sephadex G-15 columns. Certain of those fractions were further separated by paper chromatography in butanol : acetic acid : water (4 : 1 : 1) and the COH-inhibitor was localized. The pineal COH-inhibitor could also be localized by high pressure, reverse phase liquid chromatography. More COH-inhibiting activity was extracted with the Bensinger method than with aqueous and acetic acid extraction methods used earlier by us. The Cheesman extraction method for arginine vasotocin gave less regular results in our hands than the Bensinger extraction method.


Osteoarthritis. A new neurological method of pain control.
A new method of treating osteoarthritis of the knee involving the intraneural injection of a depot steroid is described. The results are superior to those produced by the more conventional systemic or intra-articular routes of steroid application. These clinical results throw light on the possible aetiology of pain in osteoarthritis.


A LewisX glycoprotein screen identifies the low density lipoprotein receptor-related protein 1 (LRP1) as a modulator of oligodendrogenesis in mice.
In the developing and adult CNS multipotent neural stem cells reside in distinct niches. Specific carbohydrates and glycoproteins are expressed in these niche microenvironments which are important regulators of stem cell maintenance and differentiation fate. LewisX (LeX), also known as stage-specific embryonic antigen-1 or CD15, is a defined carbohydrate moiety expressed in niche microenvironments of the developing and adult CNS. LeX-glycans are involved in stem cell proliferation, migration, and stemness. A few LeX carrier proteins are known, but a systematic analysis of the targets of LeX glycosylation in vivo has not been performed so far. Using LeX glycosylation as a biomarker we aimed to discover new glycoproteins with a potential functional relevance for CNS development. By immunoaffinity chromatography we enriched LeX glycoproteins from embryonic and postnatal mouse brains and used one-dimensional nLC-ESI-MS/MS for their identification. We could validate phosphacan, tenascin-C, and L1-CAM as major LeX carrier proteins present in vivo. Furthermore, we identified LRP1, a member of the LDL receptor family, as a new LeX carrier protein expressed by mouse neural stem cells. Surprisingly, little is known about LRP1 function for neural stem cells. Thus, we generated Lrp1 knock-out neural stem cells by Cre-mediated recombination and investigated their properties. Here, we provide first evidence that LRP1 is necessary for the differentiation of neural stem cells toward oligodendrocytes. However, this function is independent of LeX glycosylation.


Evolution of the 5 S RNA genes in vertebrates.
We have built the phylogenetic tree of Vertebrate 5S RNA using the sequence data of thirteen species belonging to six groups. Evolution of the 5S genes has been very slow in Vertebrates since 90 residues are identical in all 5S RNAs which are presently sequenced. In Amphibians and Teleosts different 5S genes are active in oocytes and in somatic cells. This dual gene system has probably been acquired independently by Amphibians and Teleosts. In Amphibians, the oocyte-type 5S genes have evolved much faster than the somatic-type genes. This is not true in all species since the oocyte-type genes of one Teleost (Tinca tinca) have evolved more slowly than the somatic-type genes. There are in all Vertebrate 5S RNAs five complementary regions which can be base-paired. The sequence data are compatible with the three secondary-structure models that have been proposed for 5S RNA.


Beneficial effects of tandospirone on ataxia of a patient with Machado-Joseph disease.
Tandospirone citrate (tandospirone) is an anti-anxiety drug that acts by combining with serotonin receptor (5-hydroxytryptamine-1 A [5-HT1A]). Recently, there have been a few reports of its potential role in the treatment of cerebellar ataxia. We report the first case of a patient with Machado-Joseph disease in which we successfully treated cerebellar ataxia. In addition, his leg pain, insomnia, anorexia, and depression, which are thought to be related to 5-HT1A receptors, were also remarkably alleviated by treatment with tandospirone.


Dosimetric comparison and biological evaluation of PET- and CT-based target delineation for LA-NSCLC using auto-planning.
Using auto-planning, the dosimetric and biological differences between PET- and CT-based target delineation in LA-NSCLC were studied. Twenty-three patients with IIIA-IIIB NSCLC were included in this retrospective study. For each patient, two AP plans (Plan_PET, Plan_CT) were generated based on PET- and CT-based gross tumor volume (GTVPET, GTVCT). The volume, boundary and center of mass (COM) of GTVPET and GTVCT were compared. Dosimetric indicators such as mean lung dose (MLD) and so on were evaluated. Tumor control probability (TCP) of GTVPET and GTVCT and normal tissue complication probability (NTCP) of total lung and heart were calculated. A paired-samples t-test was used to check for significant differences (p < 0.05) between dataset. Volume of GTVPET was significantly smaller than that of GTVCT. Under the premise that GTVPET met the clinical requirements in Plan_PET, GTVCT couldn't satisfy the requirements. GTVCT met the clinical requirements in Plan_CT, and four cases of GTVPET could not satisfy the requirements. Compared with Plan_CT, Plan_PET significantly reduced MLD, V5, V10, V13, V15, V20, V30 and V40 of total lung, and MHD, V30 and V40 of heart, and MUs. No significant difference was observed with respect to Dmax of spinal cord. TCP of GTVPET in Plan_PET was significantly higher than that of GTVCT. NTCP of total lung in Plan_PET was significantly lower than that in Plan_CT. There were differences in volume, boundary, and COM of targets based on the two delineation methods. These led to differences in dosimetric and biological indicators. For LA-NSCLC, the way that most hospitals only use CT to delineate the target should be careful consideration.


Regional and laminar distribution of choline acetyltransferase immunoreactivity in the cat superior colliculus.
The pattern of distribution of cholinergic fibers was examined immunohistochemically in the cat superior colliculus by using a monoclonal antibody against choline acetyltransferase (ChAT). In the superficial layers, an obvious immunoreactive zone was found in the rostral two-thirds of the outer portion of the superficial gray layer (SGS), with increasing immunoreactive intensity at the rostral pole of the colliculus. A mesh-like distribution of the immunoreactive fibers was found throughout the deeper portion of this layer with a higher concentration in the caudal levels. In the deeper collicular layers, a number of ChAT-immunoreactive fibers were seen in the outer portion of the intermediate gray layer (SGI) in a patch-like fashion. A few fibers were also immunoreactive in the deeper portion of the SGI and in the medial aspect of the deep gray layer. The density of the immunoreactivity in the deeper layers increased in the caudal levels. After unilateral destruction of the parabigeminal nucleus, the ChAT immunoreactivity was markedly reduced in the rostral aspect of the contralateral SGS, and moderately in the caudal aspect of the ipsilateral SGS.


Increased platelet sodium-proton exchange rates in insulin-dependent (type 1) diabetic patients with nephropathy and hypertension.
In order to assess the potential role of the plasma membrane sodium-proton (Na+/H+) exchanger in the pathogenesis of diabetic nephropathy, we investigated 32 insulin dependent (type 1) diabetic patients and 21 control subjects. We tested the Na+/H+ exchange as the rate of amiloride sensitive and sodium dependent volume gain of platelets suspended in sodium propionate. Patients with diabetic nephropathy had significantly increased rates of Na+/H+ exchange (0.31 +/- 0.06 s-1 x 10(-2)) when compared to those without nephropathy (0.24 +/- 0.07, p less than 0.05) or to a control group (0.23 +/- 05, p less than 0.05). Nine patients who were classified as hypertensive had a highly significant increase in the Na+/H+ exchange rates when compared to 23 non-hypertensive diabetic patients: 0.33 +/- 0.04 versus 0.24 +/- 0.06 (p less than 0.001). There was no significant correlation between the Na+/H+ exchange rates and age, diabetes duration, glycated hemoglobin or fructosamine levels on the day of the test. In summary, the data presented here demonstrate an increase in the Na+/H+ exchange rate in insulin-dependent diabetic patients with nephropathy and hypertension.


[Choice of a spin label probe in order to study the recombination of beta-hydroxybutyrate dehydrogenase of a rat liver inner mitochondrial membrane with lecithin vesicles].
We find from studying the inhibitory effect of N-ethylmaleimide (NEM) on the enzymatic activity of beta-hydroxybutyrate dehydrogenase, that approximately one molecule of NEM is bound for one molecule of protein when the enzymatic activity is completely inhibited. Since the protein is a dimer this implies that each molecule of protein possesses only one thiol group in its catalytic center. Two long chain maleimide derivates: (10.3) NEM and (1.14) NEM conform, if a reasonable assumption is accepted to the conditions required for the study of the recombination of beta-hydroxybutyrate dehydrogenase with lecithin vesicles by spin label technique.


The Tam formula: A pilot study for a new treatment for melasma.
Melasma is a common hyperpigmentation disorder with numerous, but often unsatisfactory treatment options. A pilot study to evaluate the efficacy and safety of a novel topical combination of 12% hydroquinone, 6% kojic acid, and 5% vitamin C cream for melasma. A pilot study of 6 women with melasma was conducted at an academic dermatology department and a private dermatology practice to evaluate the efficacy of a topical combination of 12% hydroquinone, 6% kojic acid, and 5% vitamin C cream, entitled the "Tam Formula." Two blinded evaluators calculated Melasma Area and Severity Index (MASI) Scores before and after treatment to evaluate change from baseline, and statistical analysis was performed. Treatment with this combination topical cream resulted in an average 63.77 ± 22.10 percent reduction in MASI scores. While there is a need for further investigation, this pilot study indicates the Tam Formula may provide an alternative treatment option for melasma.


Directionally Sensitive Fractal Radiomics Compatible With Irregularly Shaped Magnetic Resonance Tumor Regions of Interest: Association With Osteosarcoma Chemoresistance.
Computational analysis of routinely acquired MRI has potential to improve the tumor chemoresistance prediction and to provide decision support in precision medicine, which may extend patient survival. Most radiomic analytical methods are compatible only with rectangular regions of interest (ROIs) and irregular tumor shape is therefore an important limitation. Furthermore, the currently used analytical methods are not directionally sensitive. To implement a tumor analysis that is directionally sensitive and compatible with irregularly shaped ROIs. Retrospective. A total of 54 patients with histopathologic diagnosis of primary osteosarcoma on tubular long bones and with prechemotherapy MRI. A 1.5 T, T2-weighted-short-tau-inversion-recovery-fast-spin-echo. A model to explore associations with osteosarcoma chemo-responsiveness included MRI data obtained before OsteoSa MAP neoadjuvant cytotoxic chemotherapy. Osteosarcoma morphology was analyzed in the MRI data by calculation of the nondirectional two-dimensional (2D) and directional and nondirectional one-dimensional (1D) Higuchi dimensions (Dh). MAP chemotherapy response was assessed by histopathological necrosis. The area under the receiver operating characteristic (ROC) curve (AUC) evaluated the association of the calculated features with the actual chemoresponsiveness, using tumor histopathological necrosis (95%) as the endpoint. Least absolute shrinkage and selection operator (LASSO) machine learning and multivariable regression were used for feature selection. Significance was set at <0.05. The nondirectional 1D Dh reached an AUC of 0.88 in association with the 95% tumor necrosis, while the directional 1D analysis along 180 radial lines significantly improved this association according to the Hanley/McNeil test, reaching an AUC of 0.95. The model defined by variable selection using LASSO reached an AUC of 0.98. The directional analysis showed an optimal predictive range between 90° and 97° and revealed structural osteosarcoma anisotropy manifested by its directionally dependent textural properties. Directionally sensitive radiomics had superior predictive performance in comparison to the standard nondirectional image analysis algorithms with AUCs reaching 0.95 and full compatibility with irregularly shaped ROIs. 3 TECHNICAL EFFICACY: Stage 1.


Metabolic alkalosis following mitral valvuloplasty in a dog with preoperative acute kidney injury.
An 11-year-old sexually intact male Shih Tzu diagnosed with acute kidney injury and left-sided congestive heart failure that had nonelective mitral valve surgery. Metabolic alkalosis developed postoperatively, and plasma bicarbonate concentration peaked 2 days after surgery (40.2 mmol/L; pH, 7.550). Acetazolamide administration increased the urinary excretion of bicarbonate and contributed to the improvement of the dog's acid-base status and oxygenation capacity. Metabolic alkalosis persisted for 4 days after surgery, and no treatment was required after resolution. Plasma urea nitrogen and creatinine concentrations normalized 2 days after surgery. Severe metabolic alkalosis can occur as a complication following mitral valve surgery. Acetazolamide may be suitable for the treatment of severe metabolic alkalosis.


Establishing the dose of memory support to improve patient memory for treatment and treatment outcome.
Patient memory for the contents of treatment sessions is poor and this is associated with worse treatment outcome. Preliminary findings indicate that treatment provider use of memory support can be helpful in enhancing patient memory for treatment and improving outcome. The development of a novel Memory Support Intervention is currently underway. A key step in this process is to establish the dose of memory support that treatment providers deliver in treatment-as-usual, as well as the optimal dose of memory support needed to maximize patient memory for treatment points and outcomes. Forty-two adults with major depressive disorder (MDD) were randomized to receive either cognitive therapy plus memory support (CS + Memory Support; n = 22) or cognitive therapy as-usual (CT-as-usual; n = 20). Patients completed a free recall of treatment points task at post-treatment. Outcome measures were administered at baseline and post-treatment. Treatment providers delivering CT-as-usual used, on average, 8.39 instances of memory support and 3.40 different types of memory support per session. Receiver Operating Characteristics (ROC) analyses using the combined sample indicate that 12.45 instances of memory support and 3.88 to 4.13 different types of memory support are needed to maximize patient recall and functional outcome. Dosing recommendations were established using a limited sample of participants receiving cognitive therapy for MDD. Treatment providers appear to deliver a suboptimal amount of memory support. Delivering the optimal dose of memory support could improve treatment outcome.


Agonist-evoked changes in cytosolic pH and calcium concentration in human platelets: studies in physiological bicarbonate.
1. Cytosolic pH (pHi) and calcium concentration ([Ca2+]i) have been investigated in the presence and absence of physiological HCO3- in human platelets co-loaded with the fluorescent indicators BCECF and Fura-2. Basal pHi and changes evoked by butyrate, thrombin, platelet activating factor (PAF), ADP and phorbol ester were investigated, as were the effects of removing external Na+. 2. In the presence of physiological HCO3- and CO2, basal pHi was 7.02 +/- 0.04 compared with 7.15 +/- 0.05 in the absence of HCO3-. Estimated cytosolic buffering power was reduced from 35.6 +/- 3.0 to 14.5 +/- 0.4 mM/pH unit by the omission of HCO3-. 3. Thrombin evoked an immediate acidification of 0.03 +/- 0.01 pH units in the presence of HCO3- and 0.07 +/- 0.01 pH units in its absence. The acidifications were followed by a slow alkalinization. The final pHi was 0.10 +/- 0.01 units above basal in the presence of HCO3- and 0.08 +/- 0.02 units above basal in the absence of HCO3-. The initial acidification was significantly greater in the absence of HCO3-. The subsequent increase in pHi was similar in the presence and absence of this ion, but the calculated loss of proton equivalents was greater in the presence of HCO3-. 4. Replacement of extracellular Na+ with N-methyl-D-glucamine resulted in a fall in basal pHi and abolished recovery from thrombin-evoked acidification in both the presence and absence of HCO3-. 5. In the presence of HCO3-, PAF and ADP evoked an intracellular acidification similar to that caused by thrombin. However, with PAF and ADP, the subsequent recovery in pHi was slow and did not rise above basal levels. Phorbol dibutyrate, an activator of protein kinase C, evoked a similar elevation in pHi of 0.04 +/- 0.01 units over 3 min in the presence and absence of HCO3-. 6. Stopped-flow fluorimetric measurements were made of both BCECF and Fura-2 fluorescence in the presence of HCO3-. In the presence and absence of external Ca2+, thrombin-evoked rises in [Ca2+]i peaked before any cytoplasmic alkalinization occurred. ADP evoked rapid elevations in [Ca2+]i, but caused no alkalinization.(ABSTRACT TRUNCATED AT 400 WORDS)


Thromboelastography: a review for radiologists and implications on periprocedural bleeding risk.
Thromboelastography (TEG) and rotational thromboelastometry are emerging technologies that are gaining increasing acceptance in the medical field to evaluate the coagulation status of patients on an individual level by assessing dynamic clot formation. TEG has been proven to reduce blood product use as well as improve patient outcomes in a variety of medical settings, including trauma and surgery due to the expediated nature of the test as well as the ability to determine specific deficiencies present in whole blood that are otherwise undetectable with traditional coagulation studies. Currently, no guidelines or recommendations are in place for the utilization of TEG in interventional or diagnostic radiology although access to TEG has become increasingly common in recent years. This manuscript presents a review of prior literature on the technical aspects of TEG as well as its use in various fields and explains the normal TEG-tracing parameters. Common hemodynamic abnormalities and their effect on the TEG tracing are illustrated, and the appropriate treatments for each abnormality are briefly mentioned. TEG has the potential to be a useful tool for determining the hemodynamic state of patients in both interventional and diagnostic radiology, and further research is needed to determine the value of these tests in the periprocedural setting.


Mechanistic elucidation of the degradation and transformation of hydroxy-α-sanshool and its conformers as the pungent dietary components in Sichuan pepper: A DFT study.
To better understand the structural changes of sanshool pungent dietary components during the process and preservation of Sichuan pepper and pungent foods, the mechanistic insights into the intrinsic degradation and transformation of 16 hydroxy-α-sanshool conformers have been explored computationally. Our results have revealed that increasing the cis-CC bond numbers in the most stable all-trans hydroxy-β-sanshool structure causes the maximum 34.21 kJ/mol conformational energetic difference, and the existent probability of C2nnn would be lower than that of C1nnn (n = 1,2). The isomerization between the conformers could be much easier when they are excited by light radiation, as the strength of the CC bonds and their connected CC bonds becomes significantly close, and the relative energies among conformers are largely reduced. Besides, the different combination of cis/trans-CC bonds changes the delocalization degree of molecular Frontier orbitals, which consequently causes the different photochemical stability. Finally, the possible molecular oxidation degradation mechanism is proposed.


Increased prostacyclin and thromboxane A2 formation in human varicose veins.
Increased urinary metabolites of the antiaggregatory vasodilator prostacyclin (PGI2) and the proaggregatory vasoconstrictor thromboxane A2 (TXA2) have been reported in deep vein thrombosis; however, the tissue(s) of origin is uncertain. Because little is known about the formation of PGI2 or TXA2 from its common precursor, prostaglandin (PG) endoperoxide H2 (PGH2), by varicose veins, we determined the formation of 6-keto-PGF1 alpha (the stable metabolite of PGI2), TXB2 (the stable metabolite of TXA2), and PGE2. Segments of normal saphenous vein and varicose vein (nine and six patients, respectively) were incubated with 10 microM [14C]PGH2 for 2 min at 37 degrees C; products were separated by thin-layer chromatography. Surface area and mass of normal and varicose vascular segments were 19.5 +/- 0.8 versus 18.8 +/- 0.6 mm2 and 11.6 +/- 1.4 versus 10.7 +/- 0.7 mg, respectively. Formation of 6-keto-PGF1 alpha and TXB2 by the segments of varicose vein was significantly increased over that of normal vein: 157 +/- 14 versus 243 +/- 17 pmole of 6-keto-PGF1 alpha (P less than 0.005) and 22 +/- 3 versus 35 +/- 5 pmole of TXB2 (P less than 0.01). The formation of PGE2 by segments of varicose vein was not significantly different from that of normal vein (201 +/- 9 vs 219 +/- 11, respectively). Deoxyribonucleic acid (DNA) content of normal and varicose vein was 1.69 +/- 0.12 and 1.51 +/- 0.13 mg per gram of tissue, respectively. The data suggest that the increased PGI2 formation may reflect increased activity or content of PGI2 synthase. The increase in TXA2 formation may reflect increased productivity or an increased presence of residual platelets or microemboli.


Evaluation of relapse after orthodontic therapy combined with orthognathic surgery in the treatment of skeletal class III.
Multidisciplinary treatment of skeletal malocclusion by orthognathic surgery in addition to orthodontics is a routine strategy believed to offer good functional and esthetic outcomes. Postoperative relapse is, however, a problem. The present study was conducted to analyze the stability of outcomes achieved by surgical treatment of skeletal class III patients in terms of the rate and extent of relapses. A total of 30 patients who had undergone orthodontic treatment combined with orthognathic surgery were included. The primary inclusion criterion was a skeletal class III treated by mandibular setback (Obwegeser/Dal Pont) surgery alone or combined with maxillary advancement (Le Fort I) surgery. Analysis was based on one preoperative and two postoperative cephalograms per patient. We observed relapse (defined, in accordance with Proffit, as changes >2 mm or 2°) at a rate of 24% after bimaxillary procedures, compared to a lower rate of 21% after mandibular setback procedures only. The relapse rate was 21% among patients who had undergone upper-jaw surgery versus 27% among those who had undergone lower-jaw surgery, which was statistically significant. The majority of patients exhibited stable treatment outcomes. Maxillary advancement procedures were found to be less susceptible to relapse-resulting in more stable outcomes-and mandibular setback distances correlated positively with the degree of the relapse. No statistically significant differences were observed between the procedures conducted in both jaws versus in the lower jaw only, or in the extent of upper-jaw repositioning.


Correlation between liver scintigraphy and computed tomography in the detection of liver metastases.
Parallel scintigraphic and computed tomographic (CT-scan) examinations of the liver were carried out during the same observation period in 55 cancer patients in whom the liver status could be microscopically and macroscopically documented with regard to presence or absence of metastases. Scintigraphy was realized by means of 198Au or 99mTc-colloid using a rectilinear scanner or a gamma-camera; CT-scan images of the liver were obtained by a standard commercial instrument before and after injection of a contrast product. The liver was found to be normal in 38 out of the 55 observed patients and a metastatic involvement was seen in 17 cases. In 45 out of 55 cases, there was concordance between the results obtained by the two investigation methods and discordance in 10 cases. The sensitivity is 97% for the scintigraphy, 94% for the CT-scan and 100% for the common negative results. The specificity can be established as 64% for the scintigraphy, 65% for the CT-scan and 74% for common positive findings. It seems therefore that these two techniques present the same efficiency in the detection of liver metastases and that the results obtained are only partly complementary.


Association between baseline body mass index and overall survival among patients over age 60 with acute myeloid leukemia.
Acute myeloid leukemia (AML) is more common and more lethal among patients over the age of 60. Increased body mass index (BMI) has been associated with a higher incidence of various malignancies, including AML. We sought to determine whether patient BMI at the time of AML diagnosis is related to overall survival (OS) among elderly patients. We identified 97 patients with AML diagnosed after the age of 60 and treated with cytarabine-based induction chemotherapy. The median age was 68 years (range 60-87); 52% of patients were male, and our study population was predominantly white (89% of patients). The median OS for all patients was 316 days (95% CI 246-459). The hazard ratio for mortality was increased among patients with a BMI < 25 compared to BMI ≥ 30 (HR 2.14, P = 0.009, 95% CI 1.21-3.77), as well as with older age (HR 1.76, P = 0.015, 95% CI 1.12-2.79) and with secondary versus de novo disease (HR 1.95, P = 0.006, 95% CI 1.21-3.14). After multivariable analysis, we did not find a significant association between OS and other potential confounders such as coronary artery disease or diabetes among these patients. We conclude that increased BMI was independently associated with improved OS among older AML patients at our institution.


Simple models for the analysis of binding protein-dependent transport systems.
Mathematical modeling was used to evaluate experimental data for bacterial binding protein-dependent transport systems. Two simple models were considered in which ligand-free periplasmic binding protein interacts with the membrane-bound components of transport. In one, this interaction was viewed as a competition with the ligand-bound binding protein, whereas in the other, it was considered to be a consequence of the complexes formed during the transport process itself. Two sets of kinetic parameters were derived for each model that fit the available experimental results for the maltose system. By contrast, a model that omitted the interaction of ligand-free binding protein did not fit the experimental data. Some applications of the successful models for the interpretation of existing mutant data are illustrated, as well as the possibilities of using mutant data to test the original models and sets of kinetic parameters. Practical suggestions are given for further experimental design.


Qualitative analysis of cocaine and heroin users' main partner sex-risk behavior: is safety in love safety in health?
In 2009, 27% of the 48,100 estimated new cases of HIV were attributed to heterosexual contact with an infected or at-risk person. Sexually active adults are less likely to use condoms in relationships with main partners than with non-regular partners, despite general knowledge that condom use reduces HIV transmission. The purpose of this secondary qualitative analysis was to explore and contextualize perceptions of main partnerships, HIV risk, and attitudes toward condom use within main partner relationships among a subsample of intervention-arm cocaine- and/or heroin-using patients enrolled in a negative trial of brief motivational intervention to reduce the incidence of sexually transmitted disease and unsafe sexual behaviors. The open-ended portion of these interview audiotapes consisted of questions about perceptions of risk and attitudes about condom use with main partners. Enrollees were aged 18-54, English or Spanish speaking, and included in this analysis only if they reported having a main partner. We identified codes and elaborated important themes through a standard inductive three step coding process, using HyperRESEARCH™ software. Among 48 interviewees, 65% were male, half were non-Hispanic white, over 60% were 20-39 years of age, 58% had intravenous drug use (IDU), and 8% were HIV-positive. Participants defined respect, support, trust, and shared child-rearing responsibility as the most valued components of main partner relationships. Condom use was viewed occasionally as a positive means of showing respect with main partners but more often as a sign of disrespect and a barrier to intimacy and affection. Enrollees appraised their partners' HIV risk in terms of perceptions of physical health, cleanliness, and sexual and HIV testing history. They based decisions regarding condom use mainly on perceived faithfulness, length of involvement, availability of condoms, and pregnancy desirability. Risk appraisal was commonly based on appearance and subjective factors, and condom use with main sexual partners was described most often as a demonstration of lack of trust and intimacy. NCT01379599.


Prospective randomized study on asymptomatic severe carotid stenosis and perioperative stroke risk in patients undergoing major vascular surgery: prophylactic or deferred carotid endarterectomy?
We compared the perioperative (30-day) stroke risk in asymptomatic patients with severe carotid stenosis who underwent carotid endarterectomy (CEA) before or after major vascular surgery. Seventy-nine patients with asymptomatic severe carotid lesion were randomly assigned to group I (n = 40) or group II (n = 39) to receive prophylactic CEA (within 1 week before major surgery) or deferred CEA (between 30 days and 6 months after major surgery), respectively. All procedures were eversion CEAs performed under deep general anesthesia and cerebral protection involving continuous electroencephalographic monitoring for selective shunting. There were no perioperative deaths or strokes relating to the major surgical procedure in either group. All group II patients underwent deferred CEA as planned (median 47 days, range 38-94) with no subsequent perioperative deaths or strokes. Two of these patients (5.1%) suffered a minor stroke, however, 65 and 78 days after their major surgical procedure, while awaiting carotid revascularization. Although data emerging from this analysis indicate that severe asymptomatic carotid disease may be safely postponed in patients undergoing major noncarotid vascular surgery, only a multicenter prospective study could determine the most appropriate management of this subset of patients.


Paediatric subarachnoid haemorrhage and severe vasospasm secondary to traumatic pseudoaneurysm of a fenestrated vertebral artery: a case report and review of the literature.
Paediatric intracranial aneurysms are rare entities accounting for less than 5% of all age intracranial aneurysms. Traumatic aneurysms are more common in children and have an association with anatomical variations such as arterial fenestrations. Here, we present a case of a child initially presenting with traumatic subarachnoid haemorrhage who returned to baseline and was discharged home only to return within 2 weeks with diffuse subarachnoid and intraventricular re-haemorrhage. A dissecting aneurysm of a duplicated (fenestrated) V4 vertebral artery segment was identified as a rare cause of rebleeding. We describe a course complicated by severe vasospasm delaying aneurysm detection and treatment. Dissecting aneurysms in children should be considered in all cases of delayed post-traumatic cranial rebleeding, particularly where there is anomalous arterial anatomy.


Recent progress on the role of miR-140 in cartilage matrix remodelling and its implications for osteoarthritis treatment.
Cartilage matrix remodelling homeostasis is a crucial factor in maintaining cartilage integrity. Loss of cartilage integrity is a typical characteristic of osteoarthritis (OA). Strategies aimed at maintaining cartilage integrity have attracted considerable attention in the OA research field. Recently, a series of studies have suggested dual functions of microRNA-140 (miR-140) in cartilage matrix remodelling. Here, we discuss the significance of miR-140 in promoting cartilage formation and inhibiting degeneration. Additionally, we focused on the role of miR-140 in the chondrogenesis of mesenchymal stem cells (MSCs). Of note, we carefully reviewed recent advances in MSC exosomes for miRNA delivery in OA treatment.


Stress reactions among participants in mass casualty simulations.
Specific stress reactions have been observed in health care providers involved in disaster relief and mass casualty care. To determine whether similar stress reactions occurred in mass casualty simulations, we observed the participants in five large military mass casualty simulations. Using a framework of specific questions, descriptive data were obtained using direct observation and discussion with participants by faculty present to evaluate the exercise. Observations revealed that stress reactions occurred consistently during these mass casualty simulations, and these reactions resembled those seen in health care workers involved in actual mass casualty care. Application of this information to disaster medicine training for emergency physicians is discussed.


Neurospora crassa invertase. A study of amino acids at the active center.
1. The effects on Neurospora crassa invertase (beta-D-fructofuranoside fructohydrolase, EC 220.127.116.11) of a variety of group specific reagnets and other potential inhibitors were determined during a search for an irreversible inhibitor of the enzyme. Aniline, pyridoxal, enzyme substrate and products did not inactivate invertase under reducing conditions. Bromoacetic acid, iodoacetic acid, iodoacetamide, p-chloromercuribenzoate, hydroxylamine and 2-hydroxy-5-nitrobenzyl bromide were also ineffective. Iodine was the only reagent which irreversibly inhibited invertase. 2. Invertase was rapidly inactivated by low concentrations of iodine, indicating specific inhibition. However, the enzyme could not be protected from this inactivation by substrate. It was not reactivated by mercaptoethanol or cysteine. 3. Experiments on the uptake of radioactive iodine demonstrated that invertase is not iodinated under the conditions of iodine inactivation. 4. The sedimentation (S20,w) value of invertase was not altered by iodine inactivation. One-dimensional electrophoresis and finger-printing of tryptic digests revealed no differences between iodine treated and untreated invertase. There was no loss of carbohydrate from this glycoprotein during iodine inactivation. 5. Standard amino acid analyses of iodine-inactivated invertase showed some loss of tyrosine and a trace amount of methionine sulfone. Attempts to demonstrate oxidation of methionine to the sulfone, through modification of the procedure for preparation of samples for analysis, were unsuccessful. However, oxidation of half-cystine was indicated and further loss of tyrosine noted. A hypothesis is advanced that half-cystine is oxidized by iodine to a normally unstable oxidation state which is maintained and protected by its protein invironment and that loss of tyrosine may be an artifact caused by the presence of this residue during acid hydrolysis.


Artificial Intelligence and Its Effect on Dermatologists' Accuracy in Dermoscopic Melanoma Image Classification: Web-Based Survey Study.
Early detection of melanoma can be lifesaving but this remains a challenge. Recent diagnostic studies have revealed the superiority of artificial intelligence (AI) in classifying dermoscopic images of melanoma and nevi, concluding that these algorithms should assist a dermatologist's diagnoses. The aim of this study was to investigate whether AI support improves the accuracy and overall diagnostic performance of dermatologists in the dichotomous image-based discrimination between melanoma and nevus. Twelve board-certified dermatologists were presented disjoint sets of 100 unique dermoscopic images of melanomas and nevi (total of 1200 unique images), and they had to classify the images based on personal experience alone (part I) and with the support of a trained convolutional neural network (CNN, part II). Additionally, dermatologists were asked to rate their confidence in their final decision for each image. While the mean specificity of the dermatologists based on personal experience alone remained almost unchanged (70.6% vs 72.4%; P=.54) with AI support, the mean sensitivity and mean accuracy increased significantly (59.4% vs 74.6%; P=.003 and 65.0% vs 73.6%; P=.002, respectively) with AI support. Out of the 10% (10/94; 95% CI 8.4%-11.8%) of cases where dermatologists were correct and AI was incorrect, dermatologists on average changed to the incorrect answer for 39% (4/10; 95% CI 23.2%-55.6%) of cases. When dermatologists were incorrect and AI was correct (25/94, 27%; 95% CI 24.0%-30.1%), dermatologists changed their answers to the correct answer for 46% (11/25; 95% CI 33.1%-58.4%) of cases. Additionally, the dermatologists' average confidence in their decisions increased when the CNN confirmed their decision and decreased when the CNN disagreed, even when the dermatologists were correct. Reported values are based on the mean of all participants. Whenever absolute values are shown, the denominator and numerator are approximations as every dermatologist ended up rating a varying number of images due to a quality control step. The findings of our study show that AI support can improve the overall accuracy of the dermatologists in the dichotomous image-based discrimination between melanoma and nevus. This supports the argument for AI-based tools to aid clinicians in skin lesion classification and provides a rationale for studies of such classifiers in real-life settings, wherein clinicians can integrate additional information such as patient age and medical history into their decisions.


Sensitivity of efflux-driven carrier turnover to external pH in mutants of the Escherichia coli lactose carrier that have tyrosine or phenylalanine substituted for histidine-322. A comparison of lactose and melibiose.
Two Escherichia coli lactose carrier mutants (tyrosine or phenylalanine substituted for histidine 322) were studied under conditions of net efflux or equilibrium exchange. Net lactose efflux by either mutant was 10-20-fold slower than by the parent and was sensitive to extracellular pH (5.6-8.0). The presence of extracellular lactose (equilibrium exchange) failed to accelerate loss of [14C]lactose, indicating that the step(s) rate limiting for exchange were also rate limiting for net lactose efflux. Net melibiose efflux by the Phe-322 mutant was comparable to the normal carrier, while that by the Tyr-322 mutant was 5-fold faster (pH 7.0). Melibiose efflux by either mutant was sensitive to pH (5.6-8.0). Melibiose in the extracellular medium significantly accelerated loss of [3H]melibiose from either mutant, showing that slow exchange is a sugar-specific phenomenon and not an intrinsic property of these mutants. The sugar-specific effect of these mutations could mean that the defect in these mutants is not on the path of the proton, although alternative explanations cannot as yet be eliminated. The modest effect of these mutations on the transport rate indicates that His-322 contributes a far smaller free energy increment to catalyzing of H+/galactoside cotransport than active site histidines contribute to catalyzing peptide bond hydrolysis in serine proteases. We interpret this to mean that in chemical terms the function of these catalytic histidine residues differ considerably.


No increase in cerebrospinal fluid tau protein levels in patients with vascular dementia.
Tau protein levels in cerebrospinal fluid (CSF-tau) were determined in 29 patients with old cerebrovascular disease (CVD, 21 demented and eight non-demented), 69 patients with Alzheimer's disease (AD) and 17 age-matched normal controls. The CSF-tau level in the vascular dementia (VD) group (24.0 +/- 17.0 pg/ml) was significantly lower (P < 0.0001) than that in the AD group (90.0 +/- 45.3 pg/ml), but not significantly different from that in the non-demented patients with CVD (18.1 +/- 10.2 pg/ml) or controls (20.3 +/- 13.0 pg/ml). Among the VD patients, 1/21 exceeded a cut-off value (mean +/- 2 SD of controls), whereas 8/69 of the AD patients had CSF-tau levels below this value. These findings suggest that VD constitutes a group of dementias that can be separated from AD by normal CSF-tau levels. CSF-tau determinations in combination with other clinical findings may provide another diagnostic aid in the differential diagnosis between VD and AD.


The comparative immunocytochemical distribution of 28 kDa cholecalcin (CaBP) in the hippocampus of rat, guinea pig and hedgehog.
The distribution of 28 kDa cholecalcin (calcium-binding protein, CaBP) in the hippocampal formation of the rat, guinea pig and European hedgehog was examined by immunocytochemistry. The extension of the mossy fibers (the axons of the granule cells of the dentate gyrus) was also studied using the Timm's sulfide-silver method. Cholecalcin was present in all mossy fibers. In the rat, only those pyramidal cells not reached by the labeled mossy fibers displayed cholecalcin immunoreactivity. Immunocytochemical staining of the hedgehog hippocampus showed that contacts between cholecalcin-containing mossy fibers and cholecalcin-containing pyramidal cells are possible. Consequently, the protein is probably not involved in the control of mossy fiber extension. Strikingly, no guinea pig pyramidal cells showed cholecalcin immunoreactivity. The possible involvement of cholecalcin in the differential excitability of pyramidal cells in the CA3 and CA1 areas of the hippocampus could therefore be tested in a comparative study of rat, guinea pig and hedgehog.


The rs1050450 C > T polymorphism of GPX1 is associated with the risk of bladder but not prostate cancer: evidence from a meta-analysis.
Glutathione peroxidase (GPX) is an endogenous antioxidant enzyme counteracting oxidative stress. Accumulating evidence has demonstrated that the GPX1 rs1050450 C > T polymorphism may modulate cancer risk, but the association of GPX1 rs1050450 polymorphism with bladder cancer (BC) and prostate cancer (PCa) is still inconclusive. This meta-analysis was designed to determine the exact association of GPX1 rs1050450 C > T polymorphism with the risk of bladder cancer and prostate cancer. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated to estimate the association strength. Databases of PubMed, EMBASE, and China National Knowledge Infrastructure were searched to retrieve eligible studies. In total, ten eligible studies with 6,194 participants were included. By pooling all eligible studies, we found that carriers of the variant T allele were associated with a significantly increased risk of urinary tract cancer (T vs. C: OR = 1.459 and 95% CI, 1.086-1.962; CT/TT vs. CC: OR = 1.411 and 95 % CI, 1.053-1.891). In stratified analysis, we observed that the rs1050450 C > T polymorphism was significantly associated with an increased risk of BC (T vs. C: OR = 2.111 and 95% CI, 1.020-4.368; CT/TT vs. CC: OR = 1.876 and 95% CI, 1.011-3.480), while the association was not significant for PCa. Egger's test and Begg's test revealed no publication bias. The present meta-analysis provides evidence that the GPX1 rs1050450 C > T polymorphism leads to an increased risk of BC but not the risk of PCa.


The clinical use of fibrinolytic agents.
Two fibrinolytic drugs, streptokinase and urokinase, have undergone extensive clinical evaluation in the past fifteen years. Current evidence suggests that these agents may become the drugs of choice in the treatment of certain patients with venous thrombosis and pulmonary embolism. The ultimate usefulness of fibrinolytic therapy in the treatment of thrombotic conditions other than venous thrombosis and pulmonary embolism has not yet been determined.


Thermodynamic limitations of PHB production from formate and fructose in Cupriavidus necator.
The chemolithotroph Cupriavidus necator H16 is known as a natural producer of the bioplastic-polymer PHB, as well as for its metabolic versatility to utilize different substrates, including formate as the sole carbon and energy source. Depending on the entry point of the substrate, this versatility requires adjustment of the thermodynamic landscape to maintain sufficiently high driving forces for biological processes. Here we employed a model of the core metabolism of C. necator H16 to analyze the thermodynamic driving forces and PHB yields from formate for different metabolic engineering strategies. For this, we enumerated elementary flux modes (EFMs) of the network and evaluated their PHB yields as well as thermodynamics via Max-min driving force (MDF) analysis and random sampling of driving forces. A heterologous ATP:citrate lyase reaction was predicted to increase driving force for producing acetyl-CoA. A heterologous phosphoketolase reaction was predicted to increase maximal PHB yields as well as driving forces. These enzymes were then verified experimentally to enhance PHB titers between 60 and 300% in select conditions. The EFM analysis also revealed that PHB production from formate may be limited by low driving forces through citrate lyase and aconitase, as well as cofactor balancing, and identified additional reactions associated with low and high PHB yield. Proteomics analysis of the engineered strains confirmed an increased abundance of aconitase and cofactor balancing. The findings of this study aid in understanding metabolic adaptation. Furthermore, the outlined approach will be useful in designing metabolic engineering strategies in other non-model bacteria.


COVID-19 and diabetes: Association intensify risk factors for morbidity and mortality.
Diabetes is a condition that affects a large percentage of the population and it is the leading cause of a wide range of costly complications. Diabetes is linked to a multi-fold increase in mortality and when compared to non-diabetics, the intensity and prevalence of COVID-19 ailment among diabetic individuals are more. Since its discovery in Wuhan, COVID-19 has grown rapidly and shown a wide range of severity. Temperature, lymphopenia, non-productive cough, dyspnoea, and tiredness are recognized as the characteristic of individuals infected with COVID-19 disease. In COVID-19 patients, diabetes and other related comorbidities are substantial predictors of disease and mortality. According to a recent study, SARS-CoV-2 (the virus responsible for covid-19 disease) may also lead to direct pancreatic harm, which could aggravate hyperglycemia and potentially cause the establishment of diabetes in formerly non-diabetic individuals. This bidirectional association of COVID-19 and diabetes load the burden on health care professionals throughout the world. It is recommended that gliptin medications be taken moderately, blood glucose levels must be kept under control, ACE inhibitors should be used in moderation, decrease the number of avoidable hospitalizations, nutritional considerations, and some other prevention measures, such as immunization, are highly recommended. SARS-CoV-2 may cause pleiotropic changes in glucose homeostasis, which could exacerbate the pathophysiology of pre-existing diabetes or result in new disease processes.


[Bisalbuminaemia. Three aetiologies: hereditary mutation, antibiotic therapy, pseudocyst of the pancreas (author's transl)].
The demonstration of a double albumin line on blood protein electrophoresis has important practical applications: after eliminating congenital bisalbuminaemia, with no pathological consequences, this abnormality may make it possible to detect an overdose of beta-lactamines, requiring the interruption of treatment, or a serious effusion of pancreatic origin justifying surgery.


miRNA expression in pediatric failing human heart.
miRNAs are short regulatory RNAs that can regulate gene expression through interacting with the 3'UTR of target mRNAs. Although the role of miRNAs has been extensively studied in adult human and animal models of heart disease, nothing is known about their expression in pediatric heart failure patients. Different than adults with heart failure, pediatric patients respond well to phosphodiesterase inhibitor (PDEi) treatment, which is safe in the outpatient setting, results in fewer heart failure emergency department visits, fewer cardiac hospital admissions and improved NYHA classification. We have recently shown that pediatric heart failure patients display a unique molecular profile that is different from adults with heart failure. In this study we show for the first time that pediatric heart failure patients display a unique miRNA profile, and that expression of some miRNAs correlate with response to PDEi treatment. Moreover, we show that expression of Smad4, a potential target for PDEi-regulated miRNAs, is normalized in PDEi-treated patients. Since miRNAs may be used as therapy for human heart failure, our results underscore the importance of defining the molecular characteristics of pediatric heart failure patients, so age-appropriate therapy can be designed for this population.


Benign "setting sun" phenomenon in full-term infants.
I report two normally developed infants showing benign" setting sun" phenomenon. A 2(2-12)-year-old boy and a 7-year-old boy, who were born without any complications at full term, developed brief episodes of downward gazing during sucking and crying after birth However, there were no other clinical or laboratory findings, and they developed normally. The phenomenon was not visible until 6 months and 7 months, respectively. The "setting sun" phenomenon usually indicates underlying severe brain damage and can also be seen, although rarely, in healthy full-term infants until 1 to 5 months. However, the benign "setting sun" phenomenon might exist until 6 or 7 months of age in normal infants.


Compartmental force and contact location sensing in instrumented total knee replacements.
For the past three decades, total knee replacement has become the main solution for progressed knee injuries and diseases. Due to a lack of postoperative in vivo data, a universal correlation between intra- and postoperative soft tissue balance in the knee joint has not been established. In this work, an instrumented knee implant design with six piezoelectric transducers embedded in the tibial bearing is proposed. The aim of the presented device is to measure the total and compartmental forces as well as to track the location of contact points on the medial and lateral compartments of the bearing. A numerical analysis using finite element software is first performed to obtain the best sensory system arrangement inside the bearing. The chosen design is then used to fabricate a prototype of the device. Several experiments are designed and performed using the prototype, and the ability of the proposed system to track the location and magnitude of applied compartmental forces on the bearing is evaluated. The experimental results show that the instrumented knee bearing is able to accurately measure the compartmental force quantities with a maximum error of 2.6% of the peak axial load, and the contact point locations with a maximum error of less than 1 mm.


Intestinal obstruction and cystic fibrosis: antenatal ultrasound appearance.
The diagnosis of cystic fibrosis in utero is based on amniotic fluid analysis. False negative results of this method underline the importance of antenatal ultrasonography to detect intestinal obstruction in affected fetuses.


Feedback and rewards, part II: formal and informal feedback reviews.
There are 2 major classes of feedback. One class of feedback consists of the informal, numerous conversations between various people in the organization regarding the performance, behavior, and goals of an individual. Another class of feedback consists of formal reviews held once or twice a year between a supervisor and an individual. This article discusses both types of feedback.


Extensive N nucleotide addition in junctional region of T cell receptor V gamma 5 genes rearranged in fetal liver-derived thymocytes in radiation chimera mice.
The V gamma 5 chain of T cell receptor gamma delta is preferentially expressed by murine fetal thymocytes. The fetal V gamma 5 gene is known to be homogeneous and lacks N nucleotide addition. We previously reported that V gamma 5+ cells were detected among donor-derived thymocytes from irradiated C3H/He mice soon after reconstitution with AKR/J fetal liver (FL) cells, but that only a few V gamma 5+ were detected among donor-derived thymocytes from irradiated C3H/He mice reconstituted with adult bone marrow (ABM) cells. The results suggest that preferential use of V gamma 5 is determined at the level of T cell precursor generation. In the present report, we analyzed whether the junctional region of FL-derived V gamma 5 genes in the FL chimeras is of fetal type. Sequencing analysis showed that V gamma 5 genes from FL chimeras contained extensive N nucleotide addition and were diverse both in nucleotide sequences and deduced amino acid sequences. V gamma 5 genes from donor-derived thymocytes of ABM chimeras, which by polymerase chain reaction were revealed to be less frequent than those of FL chimeras, also showed extensive N addition. Furthermore, the terminal deoxynucleotidyl transferase (TdT) gene, which encodes an enzyme that adds N nucleotides into the junctional region, was expressed at high level in the donor-derived thymocytes of FL chimeras and normal 8-week-old AKR/J thymocytes but at low level in day 17 fetal AKR/J thymocytes. Our results suggest that the preferential rearrangement of the V gamma 5 gene is determined at the level of T cell precursor generation but the homogeneous V gamma 5 sequence of fetal type is generated only in the fetal thymic microenvironment where TdT gene expression is low or absent. The nomenclature of murine TcR gamma chains is according to Reilly et al. (Nature 1986. 321: 878). The relationship between the different nomenclature systems is summarized in Takagaki et al. (J. Immunol. 1989. 141: 2112).


Honeybees with extensive foraging experience rob nectar more frequently.
Not all flower-visiting animals act as pollinators; some visitors engage in foraging nectar without pollen transfer. The tendency to rob nectar is related to visitors' morphological traits and rewards per foraging effort, and drivers of this variation within visitor species are largely unknown. Because foraging behavior is affected by foraging experience, we focused on the relationship between the tendency to rob nectar and the foraging experience of each forager. We investigated five consecutive visits of European honeybee, Apis mellifera L., on comfrey, Symphytum officinale L., in Japan. We estimated the foraging experience of A. mellifera using wing wear, categorized into six groups. Approximately 60% and 40% of A. mellifera foragers engaged in legitimate visits and nectar robbing, respectively. Moreover, most A. mellifera engaged in only one foraging tactic. The proportion of nectar robbing was related to wing wear and was higher in individuals with extensively damaged wings than those with less damaged wings. The present study suggests that extensively experienced honeybee foragers tend towards nectar robbing.


Gastric Cancer Risk in Association with Underweight, Overweight, and Obesity: A Systematic Review and Meta-Analysis.
This study aimed to investigate the risk of gastric cancer (GC) in abnormal body mass index (BMI) groups. A systematic search was carried out on Embase, PubMed/Medline, and Scopus from January 2000 to January 2023. The pooled risk ratio (RR) with a 95% confidence interval (CI) was assessed using a random-effect model. Thirteen studies with total of 14,020,031 participants were included in this systematic review. The pooled RR of GC was 1.124 (95% CI, 0.968-1.304, I2: 89.08%) in underweight class, 1.155 (95% CI, 1.051-1.270, I2: 95.18%) in overweight class, and in 1.218 (95% CI, 1.070-1.386, I2: 97.65%) obesity class. There is no difference between cardia and non-cardia gastric cancer, while non-Asian race and female gender have higher risk of cancer, as Meta-regression of obesity and overweight classes showed. These findings suggest that there is a positive association between excess body weight and the risk of GC, with a higher impact in women than men and in non-Asian than Asian populations. Since abnormal weight is tied to various diseases, including GC, healthcare experts, and policymakers should continue interventions aiming to achieve a normal BMI range.


Network pharmacology analysis of the active ingredients of Corydalis hendersonii Hemsl. and their effects on eliminating neuroinflammation and improving motor functions in MPTP-intoxicated mice.
Corydalis hendersonii Hemsl. (CH), is a traditional Tibetan medicine used in highland areas for the treatment of alpine polycythemia, ulcers and various inflammatory diseases. Its antioxidant and anti-inflammatory effects have been demonstrated in experimental mice. Loss of dopaminergic neurons due to oxidative damage is thought to be an important factor in the development of PD, the potential antioxidant, anti-inflammatory effects of CH could potentially be used for PD treatment. To identify potential targets of CH using network pharmacology and to investigate the neuroprotective effects in cultured cell models and in MPTP-intoxicated mice. The main chemical components of CH were analyzed by UPLC-MS/MS and their potential targets of action or signaling pathways were analyzed using network pharmacology. MPP + or LPS was added to SH-SY5Y or BV2 cells, respectively, to establish cellular models. MPTP was administered to C57BL/6J mice to induce inflammation and dopaminergic neuron loss as well as dyskinesia, followed by behavioral analysis to determine the role of CH in eliminating inflammation, avoiding neuron loss, and improving dyskinesia. CH contains 241 alkaloids, 213 flavonoids, 177 terpenoids and 114 phenolic compounds. The targets crossover between CH and PD yielded 210 potential therapeutic targets, especially growth factors and inflammatory pathway-related genes, such as BDNF, NF-κB, as potential key targets. In cultured cells, CHE eliminated MPP + -induced impairment of cell viability as well as LPS-induced inflammation, respectively. In mice, CHE ameliorated MPTP-induced dyskinesia and rescued the loss of dopaminergic neurons in the substantia nigra and striatum. Mechanistically, CHE effectively maintained the activity of the BDNF-TrkB/Akt signaling pathway, accordingly, inhibited inflammatory signaling pathways such as HIF-1α/PKM2 and Notch/NF-kB. CH performed well in eliminating inflammation and improving locomotor deficits in mice, and its potent active ingredients are worthy of subsequent research and development.


The effect of essential fatty acid deprivation on the metabolic transformations of [1(-14)C]linolenate in developing rat brain.
Linolenic acid undergoes rapid metabolism in the brain of 21-day-old rats. Radioactivity is rapidly transferred from linolenic acid to the C20 (n--3) fatty acids while that in docosapentaenoic acid (22 : 5 n--3) and docosahexaenoic acid (22 : 6 n--3) gradually increases. A greater proportion of the radioactivity is associated with the polyunsaturated and less with saturated and monounsaturated fatty acids in essential fatty acid-deprived rats relative to controls.


Mortality related factors on hypoxic ischemic encephalopathic patients treated with therapeutic hypothermia: an 11-year single-center experience.
Hypoxic-ischemic encephalopathy (HIE) is a condition that may cause multiple organ dysfunction and has a high rate of mortality and morbidity. Therapeutic hypothermia is the only proven treatment that decreases the sequel and mortality rate of neonates that are born after 36 weeks of pregnancy and have moderate-severe HIE. Our study was a single-center, retrospective study that includes newborns (gestational age ≥ 36 weeks) who underwent therapeutic hypothermia due to hypoxic-ischemic encephalopathy between 2010 and 2020. We evaluated 125 patients who were diagnosed with moderate to severe HIE and received therapeutic hypothermia. Demographic and clinical data were obtained from electronic medical records and patient files. The patients were separated into two groups as exitus group (n = 39) and discharged group (n = 86). We aimed to evaluate factors affecting mortality. We determined that the median resuscitation times were longer in the delivery room [retrospectively, 10th minutes (0-30) vs. 1 min (0-20), p < 0.05], the tenth min APGAR scores were lower [respectively, 4 (0-7) vs. 6 (3-10), p < 0.05], and the median pH value in the first blood gas taken was lower [respectively, 6.87 (6.4-7.14) vs. 6.90 (6.58-7.12), p < 0.05] in the exitus group. We also determined that multiple organ dysfunction is seen more often in the exitus group. This study demonstrated that the depth of acidosis in the blood gas, multiple organ dysfunction, and the existence of early-onset seizures are the signs of poor prognosis. Therefore, physicians need to be aware of such prognostic factors to follow these patients more closely in terms of possible complications and to inform their parents.


A novel POLD1 pathogenic variant identified in two families with a cancer spectrum mimicking Lynch syndrome.
The POLD1 gene is involved in DNA proofreading to ensure accurate DNA replication. Some germline alterations in its exonuclease domain are associated with predisposition to cancers and colonic polyps. Only a few pathogenic variants have been clearly identified so far. Here we report a novel variant: c.1458G>T p.(Lys486Asn) that we classified as pathogenic, detected in two putatively unrelated families. The cancer spectrum was very similar to Lynch syndrome, implying an overlapped tissue susceptibility. The common presence of colonic polyps in carriers and the MMR proficient phenotype in tumors were distinctive features suggesting POLD1 implication. Some clinical characteristics observed in the carriers of this variant differed from those reported previously, suggesting a potential genotype/phenotype correlation, and very likely in relation to the functional importance of affected residues. Our findings provide further insight into understanding the role of POLD1 in cancer-related risk.


Special AT-Rich Sequence-Binding Protein 1 Supports Survival and Maturation of Naive B Cells Stimulated by B Cell Receptors.
Epigenetic mechanisms underpin the elaborate activities of essential transcription factors in lymphocyte development. Special AT-rich sequence-binding protein 1 (SATB1) is a chromatin remodeler that orchestrates the spatial and temporal actions of transcription factors. Previous studies have revealed the significance of SATB1 in T cell lineage. However, whether and how SATB1 controls B cell lineage development is yet to be clarified. In this study, we show that SATB1 is an important factor during splenic B cell maturation. By analyzing SATB1/Tomato reporter mice, we determined the dynamic fluctuation of SATB1 expression in the B cell lineage. Although SATB1 expression decreased to minimal levels during B cell differentiation in the bone marrow, it resurged markedly in naive B cells in the spleen. The expression was dramatically downregulated upon Ag-induced activation. Splenic naive B cells were subdivided into two categories, namely SATB1high and SATB1-/low, according to their SATB1 expression levels. SATB1high naive B cells were less susceptible to death and greater proliferative than were SATB1-/low cells during incubation with an anti-IgM Ab. Additionally, SATB1high cells tended to induce the expression of MHC class II, CD86, and CD83. Accordingly, naive B cells from B lineage-specific SATB1 conditional knockout mice were more susceptible to apoptosis than that in the control group upon anti-IgM Ab stimulation in vitro. Furthermore, conditional knockout mice were less capable of producing Ag-specific B cells after immunization. Collectively, our findings suggest that SATB1 expression increases in naive B cells and plays an important role in their survival and maturation.


Primary lipogranuloma of male genitalia.
Lipogranulomas developing secondarily in the genitourinary system have been reported rather frequently, but primary lipogranulomas without any past history of etiologically related conditions are rare. We report on 2 cases recently encountered in which tumors were diagnosed as sclerosing lipogranuloma on histopathologic examination.


How Joannites' economy eradicated primeval forest and created anthroecosystems in medieval Central Europe.
During European states' development, various past societies utilized natural resources, but their impact was not uniformly spatially and temporally distributed. Considerable changes resulted in landscape fragmentation, especially during the Middle Ages. Changes in state advances that affected the local economy significantly drove trajectories of ecosystems' development. The legacy of major changes from pristine forest to farming is visible in natural archives as novel ecosystems. Here, we present a high-resolution densely dated multi-proxy study covering the last 1500 years from a peatland located in CE Europe. The economic activity of medieval societies was highly modified by new rulers-the Joannites (the Order of St. John of Jerusalem, Knights Hospitaller). We studied the record of these directorial changes noted in the peat profile. Our research revealed a rapid critical land-use transition in the late Middle Ages and its consequences on the peatland ecosystem. The shift from the virgin forest with regular local fires to agriculture correlates well with the raising of local economy and deforestations. Along with the emerging openness, the wetland switched from alkaline wet fen state to acidic, drier Sphagnum-dominated peatland. Our data show how closely the ecological state of wetlands relates to forest microclimate. We identified a significant impact of the Joannites who used the novel farming organization. Our results revealed the surprisingly fast rate of how feudal economy eliminated pristine nature from the studied area and created novel anthroecosystems.


[Mediator liberation at the neuromuscular junctions of rhythmically stimulated frog sartorius muscles].
Synapses of large fibers seem to have a more obvious initial increase followed by a greater decrease in quantum content (m) of EPPs than the small fibers. The total amount of neurotransmitter released during EPPs reproduction was much greater in the large fibres. The calculation of binomial parameters of transmitter release showed that n parameter repeated the dynamics of m, while the P parameter gradually increased. The initial uptake of P and increase of n was more obvious in verve endings of the large muscle fibres. The findings suggest an unequal length of synaptic contact.


Correlations between the benzene character of acenes or helicenes and simple molecular descriptors.
Aromatic stabilities of acenes and helicenes, which are responsible for their biological, environmental and cancerous behavior have been modeled using a newly introduced Sadhana (Sd) and A indices. The results are compared with those obtained from PI (Padmakar-Ivan) index. The regression analysis has shown that excellent results are obtained by considering acenes and helicenes as separate classes of isomeric benzenoid hydrocarbons and that A index is better index than both PI and Sd indices.


Polymers modified with double-tailed fluorous compounds for efficient DNA and siRNA delivery.
Cationic polymers are widely used as gene carriers, however, these polymers are usually associated with low transfection efficacy and non-negligible toxicity. Fluorination on polymers significantly improves their performances in gene delivery, but a high density of fluorous chains must be conjugated on a single polymer. Here we present a new strategy to construct fluorinated polymers with minimal fluorous chains for efficient DNA and siRNA delivery. A double-tailed fluorous compound 2-chloro-4,6-bis[(perfluorohexyl)propyloxy]-1,3,5-triazine (CBT) was conjugated on dendrimers of different generations and low molecular weight polyethylenimine via a facile synthesis. The yielding products with average numbers of 1-2 conjugated CBT moieties showed much improved EGFP and luciferase transfection efficacy compared to unmodified polymers. In addition, these polymers show high siRNA delivery efficacy on different cell lines. Among the synthesized polymers, generation 1 (G1) dendrimer modified with an average number of 1.9 CBT moieties (G1-CBT1.9) shows the highest efficacy when delivering both DNA and siRNA and its efficacy approaches that of Lipofectamine 2000. G1-CBT1.9 also shows efficient gene silencing in vivo. All of the CBT-modified polymers exhibit minimal toxicity on the cells at their optimal transfection conditions. This study provides a new strategy to design efficient fluorous polymers for DNA and siRNA delivery.


Intravenous versus Epidural Routes of Patient-Controlled Analgesia in Abdominal Surgery: Systematic Review with Meta-Analysis.
To compare the intravenous and epidural routes of patient-controlled anesthesia in abdominal surgery. We searched for randomized clinical trials that compared the intravenous and epidural modes of patient-controlled anesthesia in intra-abdominal surgery in adults. Data analysis was performed in RevMan 5.4. Heterogeneity was measured using I2 statistic. Risk of bias was assessed using the Jadad/Oxford quality scoring system. Seven studies reporting 529 patients were included into the meta-analysis. For pain at rest, the mean difference with 95% confidence interval (CI) was -0.00 [-0.79, 0.78], p-value 0.99, while for pain on coughing, it was 0.43 [-0.02, 0.88], p-value 0.06, indicating that patient-controlled epidural analgesia (PCEA) was superior. For the sedation score, the mean difference with 95% CI was 0.26 [-0.37, 0.89], p-value 0.42, slightly favoring PCEA. For the length of hospital stay, the mean difference with 95% CI was 1.13 [0.29, 1.98], p-value 0.009, favoring PCEA. For postoperative complications, the risk ratio with 95% CI was 0.8 [0.62, 1.03], p-value 0.08, slightly favoring patient-controlled intravenous analgesia (PCIVA). A significant effect was observed for hypotension, favoring PCIVA. Patient-controlled intravenous analgesia compared with patient-controlled epidural analgesia was associated with fewer episodes of hypotension. PCEA, on other hand, was associated with a shorter length of hospital stay. Pain control and other side effects did not differ significantly. Only three studies out of seven had an acceptable methodological quality. Thus, these conclusions should be taken with caution.


Nicorandil protects against coronary microembolization-induced myocardial injury by suppressing cardiomyocyte pyroptosis via the AMPK/TXNIP/NLRP3 signaling pathway.
Coronary microembolization (CME) is a common and intractable complication of coronary revascularization, which leads to perioperative myocardial injury, cardiac dysfunction, and poor prognosis. Nicorandil is widely used for the management of ischemic heart diseases, but the cardioprotective effects of nicorandil beyond anti-angina in CME-induced myocardial injury are worthy of further exploration. Therefore, the present study investigated the effect of nicorandil on CME-induced cardiomyocyte pyroptosis and explored the underlying mechanism. A rat model of CME was established via the injection of microspheres into the left ventricle. A cell model of H9c2 cardiomyocytes stimulated by lipopolysaccharide (LPS) and hypoxia mimicked the microenvironment induced by CME. Nicorandil or the adenosine monophosphate-activated protein kinase (AMPK)-specific inhibitor compound C (CC) was administered before CME induction and cell modeling. Cardiac function, histological alterations in the myocardium, myocardial injury biomarkers in serum and cell culture supernatant, cell viability, adenosine triphosphate (ATP) level, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, reactive oxygen species (ROS) activity, mitochondrial membrane potential, and pyroptosis-associated index were assessed after the animal and cell modeling of CME. Nicorandil pretreatment attenuated cardiac dysfunction and myocardial injury following CME. Nicorandil also alleviated oxidative stress and mitochondrial damage. Moreover, nicorandil promoted AMPK activation, reduced the expression of thioredoxin-interacting protein (TXNIP), inhibited the activation of the NOD-like receptor pyrin containing 3 (NLRP3) inflammasome, and mitigated cardiomyocyte pyroptosis. However, co-treatment with CC reversed the cardioprotective effects of nicorandil. Nicorandil pretreatment inhibits cardiomyocyte pyroptosis and alleviates CME-induced myocardial injury via the AMPK/TXNIP/NLRP3 signaling pathway.


Disrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficits.
The cell adhesion molecule nectin3 and its presynaptic partner nectin1 have been linked to early-life stress-related cognitive disorders, but how the nectin1-nectin3 system contributes to stress-induced neuronal, circuit, and cognitive abnormalities remains to be studied. Here we show that in neonatally stressed male mice, temporal order and spatial working memories, which require the medial entorhinal cortex (MEC)-CA1 pathway, as well as the structural integrity of CA1 pyramidal neurons were markedly impaired in adulthood. These cognitive and structural abnormalities in stressed mice were associated with decreased nectin levels in entorhinal and hippocampal subregions, especially reduced nectin1 level in the MEC and nectin3 level in the CA1. Postnatal suppression of nectin1 but not nectin3 level in the MEC impaired spatial memory, whereas conditional inactivation of nectin1 from MEC excitatory neurons reproduced the adverse effects of early-life stress on MEC-dependent memories and neuronal plasticity in CA1. Our data suggest that early-life stress disrupts presynaptic nectin1-mediated interneuronal adhesion in the MEC-CA1 pathway, which may in turn contribute to stress-induced synaptic and cognitive deficits.


Intravascular heat exchange technology successfully treats a patient after ultra-long cardiopulmonary resuscitation: a case report.
To investigate the effect of intravascular heat exchange in saving the lives of patients after cardiopulmonary resuscitation. The clinical data of a female patient who was given cardiopulmonary resuscitation for 1.67 h in July 2014 in our hospital was retrospectively analyzed. An intravascular heat exchange procedure was performed on the patient to control her body temperature. Comprehensive treatment measures also included mechanical ventilation, vasoactive agents, and osmotic dehydrating agents to reduce the elevated intracranial pressure, improving cerebral metabolism and anti-infective therapy. After providing an intravascular heat exchange for 6 h, the patient's eyes automatically opened but the patient was unconscious. After 28 h, the patient became conscious. The breathing machine was withdrawn after 2 d and the vasoactive agents were stopped after 5 d. The patient was discharged after 17 d. Intravascular heat exchange could be an important complementary treatment to cardiopulmonary resuscitation.


SARS-CoV-2 Seroprevalence and Cross-Variant Antibody Neutralization in Cats, United Kingdom.
Anthropogenic transmission of SARS-CoV-2 to pet cats highlights the importance of monitoring felids for exposure to circulating variants. We tested cats in the United Kingdom for SARS-CoV-2 antibodies; seroprevalence peaked during September 2021-February 2022. The variant-specific response in cats trailed circulating variants in humans, indicating multiple human-to-cat transmissions over a prolonged period.


EPR paramaters and defect structure of the trigonal Ti2+ center in ZnS.
The axial Ti2+ center in a nearly wholly cubic ZnS crystal is assigned to the Ti2+ ion on the hexagonal site of wurtzite structure caused by stacking faults. On the ground of the assignment, the EPR parameters (zero-field splitting D, g factor g( parallel) and g-anisotropy Deltag=g( parallel)-g( perpendicular)) of the axial Ti2+ center are calculated from the high-order perturbation formulas based on the cluster approach for the EPR parameters of 3d2 ion in trigonal symmetry. From the calculations, the local atom-position parameter u(loc) (which is different from the corresponding parameter u in the host wurtzite structure) and hence the defect structure of the Ti2+ center are estimated. The results (the calculated EPR parameters and the defect structure) are discussed.


Evaluation of genotoxic and cytotoxic effects in human peripheral blood lymphocytes exposed in vitro to neonicotinoid insecticides news.
Calypso (thiacloprid), Poncho (clothianidin), Gaucho (imidacloprid), and Jade (imidacloprid) are commercial neonicotinoid insecticides, a new class of agrochemicals in México. However, genotoxic and cytotoxic studies have not been performed. In the present study, human peripheral blood lymphocytes (PBL) were exposed in vitro to different concentrations of the four insecticides. The genotoxic and cytotoxic effects were evaluated using the alkaline comet and trypan blue dye exclusion assays. DNA damage was evaluated using two genotoxicity parameters: tail length and comet frequency. Exposure to 9.5 × 10(-6) to 5.7 × 10(-5) M Jade; 2.8 × 10(-4) to 1.7 × 10(-3) M Gaucho; 0.6 × 10(-1) to 1.4 × 10(-1) M Calypso; 1.2 × 10(-1) to 9.5 × 10(-1) M Poncho for 2 h induced a significant increase DNA damage with a concentration-dependent relationship. Jade was the most genotoxic of the four insecticides studied. Cytotoxicity was observed in cells exposed to 18 × 10(-3) M Jade, 2.0 × 10(-3) M Gaucho, 2.0 × 10(-1) M Calypso, 1.07 M Poncho, and cell death occurred at 30 × 10(-3) M Jade, 3.3 × 10(-3) M Gaucho, 2.8 × 10(-1) M Calypso, and 1.42 M Poncho. This study provides the first report of genotoxic and cytotoxic effects in PBL following in vitro exposure to commercial neonicotinoid insecticides.


Reproductive factors, heterogeneity, and breast tumor subtypes in women of mexican descent.
Published data support the presence of etiologic heterogeneity by breast tumor subtype, but few studies have assessed this in Hispanic populations. We assessed tumor subtype prevalence and associations between reproductive factors and tumor subtypes in 1,041 women of Mexican descent enrolled in a case-only, binational breast cancer study. Multinomial logistic regression comparing HER2(+) tumors and triple-negative breast cancer (TNBC) to luminal A tumors was conducted. Compared with women with luminal A tumors, those with a later age at first pregnancy were less likely to have TNBC [OR, 0.61; 95% confidence interval (CI), 0.39-0.95], whereas those with three or more full-term pregnancies were more likely to have TNBC (OR, 1.68; 95% CI, 1.10-2.55). A lower odds of TNBC was shown for longer menstruation duration, whether before first pregnancy (OR, 0.78; 95% CI, 0.65-0.93 per 10 years) or menopause (OR, 0.79; 95% CI, 0.69-0.91 per 10 years). Patients who reported breastfeeding for more than 12 months were over twice as likely to have TNBC than luminal A tumors (OR, 2.14; 95% CI, 1.24-3.68). Associations comparing HER2(+) with luminal A tumors were weak or nonexistent except for the interval between last full-term pregnancy and breast cancer diagnosis. Findings show etiologic heterogeneity by tumor subtype in a population of Hispanic women with unique reproductive profiles. Identification of etiologically distinct breast tumor subtypes can further improve our understanding of the disease and help provide personalized prevention and treatment regimens.