VP6 genetic diversity, reassortment, intragenic recombination and classification of rotavirus B in American and Japanese pigs.
Rotavirus B (RVB) has been identified as a causative agent of diarrhea in rats, humans, cattle, lambs, and swine. Recently, 20 RVB VP7 genotypes were determined based on an 80% nucleotide percent cut-off value. In this study, we sequenced the RVB VP6 gene segment from 80 RVB positive swine samples from the United States and Japan. Phylogenetic analyses, using the 30 available RVB VP6 sequences from GenBank and our 80 novel RVB VP6 sequences, revealed a large genetic diversity of RVB strains, mainly in pigs. For classification purposes, pairwise identity frequency analyses suggested an 81% nucleotide percent cut-off value, resulting in 13 RVB VP6 (I) genotypes. In addition, an intragenic recombinant RVB VP6 segment was identified from Japan. Furthermore, the data indicates frequent reassortment events occurred between the porcine RVB VP7 and VP6 gene segments.


Improving the politics of biotechnological innovations in food security and other sustainable development goals.
The unwarranted interference of some environmental non-governmental organisations (ENGOs) in decision-making over genetically modified (GM) crops has prompted calls for politics to be removed from the regulatory governance of these products. However, regulatory systems are inevitably political because their purpose is to decide whether the use of particular products will help or hinder the delivery of public policy objectives. ENGOs are most able to interfere in regulatory decision-making when policy objectives and decision-making criteria are vague, making the process vulnerable to disruption by organisations that have a distinct agenda. Making regulatory decision-making about GM crops and other green biotechnology more resistant to interference therefore requires better politics not the removal of politics. Better politics begins with political leadership making a case for green biotechnology in achieving food security and other sustainable development goals. Such a policy must involve making political choices and cannot be outsourced to science. Other aspects of better politics include regulatory reform to set policy aims and decision-making criteria that encourage innovation as well as control risk, and engagement with civil society that discusses the values behind attitudes to the application of green biotechnology. In short, green biotechnology for sustainable development needs better politics to counter well-organised opposition, to encourage innovation, and to build the trust of civil society for these policies. Removing politics from regulatory governance would be a gift to ENGOs that are opposed to the use of biotechnology.


The effects of hemodynamic force on embryonic development.
Blood vessels have long been known to respond to hemodynamic force, and several mechanotransduction pathways have been identified. However, only recently have we begun to understand the effects of hemodynamic force on embryonic development. In this review, we will discuss specific examples illustrating the role of hemodynamic force during the development of the embryo, with particular focus on the development of the vascular system and the morphogenesis of the heart. We will also discuss the important functions served by mechanotransduction and hemodynamic force during placentation, as well as in regulating the maintenance and division of embryonic, hematopoietic, neural, and mesenchymal stem cells. Pathological misregulation of mechanosensitive pathways during pregnancy and embryonic development may contribute to the occurrence of cardiovascular birth defects, as well as to a variety of other diseases, including preeclampsia. Thus, there is a need for future studies focusing on better understanding the physiological effects of hemodynamic force during embryonic development and their role in the pathogenesis of disease.


Normolipemic tendon and tuberous xanthomas.
Tendon and skin xanthomas have been found in association with familial hypercholesterolemia, broad beta disease, beta sitosterolemia, and cerebrotendinous xanthomatosis. We are reporting a patient with tendon and tuberous xanthomas accompanied by normal plasma lipids. In addition, the plasma and xanthoma concentration of cholestanol was normal, while beta sitosterol was absent. These data rule out the disorders listed and suggest that this patient's disorder may represent a new normolipemic xanthomatosis.


Cancer, a disease of defective glucose metabolism.
The cancer cell appears to contain two non phosphorylating glycolytic pathways in addition to phosphorylating glycolysis and the aerobic citric acid and phosphogluconate cycles. It is hypothesised that these pathways are all interconnected and in the static adult cell non phosphorylating glycolysis is in a state of controlled inactivity. Cancer occurs when one or both non phosphorylating glycolytic pathways escape from control thereby producing an autonomous flow of energy and mitosis. Both pathways appear dependent upon glutathione to convert glucose to lactic acid. The pathways can be differentiated by their responses to ionising and 434MHz non ionising radiation, hyperthermia and biochemical environmental changes in vivo.


FGF9 induces neurite outgrowth upon ERK signaling in knock-in striatal Huntington's disease cells.
Huntington's disease (HD) is a neurodegenerative disease that causes deficits in neurite outgrowth, which suggests that enhancement of neurite outgrowth is a potential direction by which to improve HD. Our previous publications showed that fibroblast growth factor 9 (FGF9) provides anti-apoptosis and anti-oxidative functions in striatal cell models of HD through the extracellular signal-regulated kinases (ERK) pathway, and FGF9 also stimulates cytoskeletons to enhance neurite outgrowth via nuclear factor kappa B (NF-kB) signaling. In this study, we further demonstrate the importance of the ERK pathway for the neurite outgrowth induced by FGF9 in HD striatal models. FGF9 was treated with ERK (U0126) or NF-kB (BAY11-7082) inhibitors in STHdhQ7/Q7 and STHdhQ111/Q111 striatal knock-in cell lines to examine neurite outgrowth, cytoskeletal markers, and synaptic proteins via immunofluorescence staining and Western blotting. NF-kB activity was analyzed by NF-kB promoter reporter assay. Here, we show that suppression of ERK signaling significantly inhibits FGF9-induced neurite outgrowth, cytoskeletal markers, and synaptic proteins in HD striatal cells. In addition, we also show suppression of ERK signaling significantly decreases FGF9-induced NF-kB activation, whereas suppression of NF-kB does not decrease FGF9-induced ERK signaling. These results suggest that FGF9 activates ERK signaling first, stimulates NF-kB upregulation, and then enhances neurite outgrowth in HD striatal cells. We elucidate the more detailed mechanisms of neurite outgrowth enhanced by FGF9 in these HD striatal cells. This study may provide insights into targeting neurite outgrowth for HD therapy.


Who Speaks for Science?
Ironically, flat-Earthers, anti-vaxxers, and climate change naysayers trust in science. Unfortunately, they trust the wrong science. That conundrum lies at the heart of scientific literacy in an age of well-funded commercial and ideological interests and overwhelming digital information. The core question for the citizen-consumer is not philosophically "why trust science?" (Oreskes 2019) but sociologically "who speaks for science?" Teachers can help students learn how to navigate the treacherous territory of inevitably mediated communication and the vulnerabilities of epistemic dependence. Students need to understand the role of science communication practices (media literacy) and the roles of credibility, expertise and honesty and the deceptive strategies used by imitators of science to seem like credible voices for science.


The impact of kin proximity on net marital fertility and maternal survival in Sweden 1900-1910-Evidence for cooperative breeding in a societal context of nuclear families, or just contextual correlations?
We investigate the association between the geographic proximity of the grandparents on net marital fertility and maternal survival in Sweden, 1900-1910, within the framework of the cooperative-breeding-hypothesis. Data were derived from Swedish full-count censuses (1880-1910) and the Swedish Death Index. Married couples were linked to their parental households. Poisson and logistic regression analyses were used to investigate the association between the geographical proximity of the grandparents on net marital fertility, which we measured as the number of surviving children born between 1900 and 1910, and the mother's survival. Models were fitted with and without fixed effects to assess the effects of unobserved characteristics shared at the parish and the family level. The results indicate that net fertility and maternal survival increased with the husband's parents' geographic proximity. In contrast, we found no evidence that the geographic proximity of the wife's parents was associated with increased fertility or maternal survival. Rather, the presence of the mother's parents in the household lowered net fertility and reduced maternal survival. This study provides evidence that kin proximity was associated with fertility and mortality of married women, and that the associations differed for paternal and maternal kin in the societal context of Swedish nuclear families (1900-1910). However, the patterns of kin proximity that we identified were correlated with characteristics such as socioeconomic status, occupation, and wealth, which also exhibited strong correlations with fertility and survival. Future research assessing the effects of kinship on demographic developments must therefore carefully consider the socio-environmental context.


Fine specificity of natural killer T cells against GD3 ganglioside and identification of GM3 as an inhibitory natural killer T-cell ligand.
GD3, a ganglioside expressed on melanoma, is the only tumour-associated glycolipid described to date that can induce a CD1d-restricted natural killer T (NKT)-cell response. We analysed the fine specificity of GD3-reactive NKT cells and discovered that immunization with GD3 induced two populations of GD3-reactive NKT cells. One population was CD4+ CD8- and was specific for GD3; the other population was CD4- CD8- and cross-reacted with GM3 in a CD1d-restricted manner, but did not cross-react with GM2, GD2, or lactosylceramide. This indicated that the T-cell receptors reacting with GD3 recognize glucose-galactose linked to at least one N-acetyl-neuraminic acid but will not accommodate a terminal N-acetylgalactosamine. Immunization with GM2, GM3, GD2, or lactosylceramide did not induce an NKT-cell response. Coimmunization of GM3-loaded antigen-presenting cells (APCs) with GD3-loaded APCs suppressed the NKT-cell response to GD3 in a CD1d-restricted manner. This suppressive effect was specific for GM3 and was a local effect lasting 2-4 days. In vitro, GM3-loaded APCs also suppressed the interleukin-4 response, but not the interferon-gamma response, of NKT cells to alpha-galactosylceramide. However, there was no effect on the T helper type 2 responses of conventional T cells. We found that this suppression was not mediated by soluble factors. We hypothesize that GM3 induces changes to the APC that lead to suppression of T helper type 2-like NKT-cell responses.


Long-term effects of calcium availability on prolactin and protein synthesis in human decidual cells.
Ever since decidual cells were recognized as the source of decidual prolactin (dPRL), very few reports have dealt with the role of calcium (Ca2+) on dPRL synthesis and release. In a recent work, we described the presence of T-type Ca2+ channels in these cells, giving Ca(2+)-dependent action potentials. However, we failed to demonstrate any action of decidual cell Ca2+ modulation on acute dPRL release, but observed only long-term effects. We have now investigated these effects on decidual protein and dPRL synthesis after 24 h treatments. When Ca2+ channel blockers or EGTA (2 mM) were added to the culture medium, dPRL release and [3H] leucine incorporation into proteins decreased. Increasing external Ca2+ up to 2 mM instead of 0.8 mM or changing the external K+ concentration (30 mM instead of 5.6) had no consequence on dPRL release, whereas 2 mM of Ca2+ enhanced total protein synthesis. No toxicity was noted with these treatments. Finally a possible effect of Ca2+ modulation on dPRL synthesis was studied using [35S] methionine. The specific activity of [35S] methionine on dPRL was similar in control and treated cells (EGTA, 2 mM Ca2+, cobalt). These results support the idea that Ca2+ controls dPRL synthesis in decidual cells, acting only on general protein synthesis processes.


Pattern formation of the otic placode and morphogenesis of the otocyst.
The early embryonic development of the inner ear anlage, from the otic placode stage to formation of the otocyst, was documented in CBA/CBA mice by scanning electron microscopy. The otic placode is identified at the eight- to ten-somite stage, as revealed by the surface morphology of the developing ectoderm. The cells in the otic depression are considerably smaller than those of the adjacent ectodermal surface. Rapid invagination of the otic anlage occurs during the ninth gestational day (approximately eight to 20 somites). In most specimens from the tenth gestational day, the otic vesicle has closed toward the ectodermal surface. The surface of the otocyst on the 13th gestational day shows considerable specialization, with regional differences of the surface structure.


Percutaneous Assist Device for Cardiopulmonary Resuscitation.
Persistent cardiac arrest is often caused by coronary ischemia. Urgent revascularization during on-going resuscitation with the support of percutaneous left ventricular assist devices (PVAD) may be feasible and can have the potential to improve the prognosis. Transport during resuscitation is a challenge that may be overcome with the use of cardiopulmonary resuscitation devices. In the catheterization laboratory, rapid deployment of PVAD may reduce ischemia, contribute to electrical stabilization of the heart, and facilitate definite treatment with percutaneous coronary intervention. After revascularization, PVAD therapy may promote myocardial recovery and improve vital organ perfusion in a critical phase.


Psychological interventions improve quality of life despite persistent pain in endometriosis: results of a 3-armed randomized controlled trial.
Despite standard medical treatment endometriosis is often associated with disabling pain and poor quality of life (QoL). Studies indicate that psychological interventions (PIs) may improve pain and QoL, yet studies on the effects of PIs for women with endometriosis are sparse and limited by low-quality study designs. Therefore, this study aimed, in a rigorous three-armed design, to evaluate the effect of PIs on chronic pelvic pain (CPP) and QoL in women with endometriosis. This three-armed parallel, multi-center randomized controlled trial included fifty-eight endometriosis patients reporting severe CPP [≥ 5 for pain intensity measured on a 0-10-point numeric rating scale (NRS)]. Patients were randomly assigned to (1) Specific mindfulness- and acceptance-based psychological intervention (MY-ENDO), (2) Carefully matched non-specific psychological intervention (Non-specific), or (3) A wait-list control group (WL). The primary outcome was pelvic pain intensity/unpleasantness measured on NRS. Secondary outcomes included endometriosis-related quality of life, workability, pain acceptance, and endometriosis-related symptoms. Differences in outcomes between groups at post-treatment follow-up were analyzed using mixed linear models. Analyses were performed on an intention-to-treat basis. Compared to WL, psychological intervention (MY-ENDO + Non-specific) did not significantly reduce pain. However, psychological intervention did significantly improve the QoL-subscales 'control and powerlessness', 'emotional well-being', and 'social support' as well as the endometriosis-related symptoms 'dyschezia' and 'constipation'. MY-ENDO was not superior to Non-specific. Women with endometriosis may have significant and large effects of psychological intervention on QoL despite an ongoing experience of severe CPP. 12 April 2016, clinicaltrials.gov (NCT02761382), retrospectively registered.


Blockade of conditioned avoidance responding by trazodone, etoperidone, and MCPP.
Phenylpiperazines, such as meta-chlorophenylpiperazine (MCPP) a serotonin agonist, have recently been reported to block conditioned avoidance responding (CAR) in the rat, which is an indication of possible antipsychotic utility. Since MCPP is a major metabolite of both antidepressant drugs trazodone (TZ) and etoperidone (ET), both were examined for activity in blocking CAR in a single-trial lever press task in Fisher 344 rats. Both TZ and ET produced dose-related falls in CAR with ED50 values (95% confidence limits) of 13.3 (9.6, 18.5) and 10.4 (8.5, 13.2) mg/kg IP, respectively. In contrast, MCPP had an ED50 value of 2.5 (1.8, 3.6) mg/kg IP TZ, ET, and MCPP were also examined for the production of catalepsy and the blockade of amphetamine-induced stereotypy to determine whether each was acting to block CAR via a dopaminergic mechanism of action. None, however, was found highly active. On the other hand, the serotonin receptor blocker metergoline (1.0 mg/kg IP) significantly reduced the CAR block produced by each, suggesting a serotonergic mechanism of action. Since TZ and ET are both less potent than MCPP, the data also suggest TZ and ET may block CAR via formation of MCPP.


Multidimensional management of a vascular injury following total knee arthroplasty: A rare case report.
Acute vascular injury during total knee arthroplasty (TKA) is an extremely rare complication, but one which can have devastating consequences threatening the limb and/or life of the patient if not diagnosed and managed at the earliest. The clinical presentation can vary from acute haemorrhage or ischemia in the peri operative period; to a delayed presentation of recurrent swelling and pain secondary to a geniculate or popliteal artery pseudoaneurysm. This is the first reported case of an acute inferolateral genicular artery haemorrhage following TKA and the associated medical complications. It was successfully managed with emergency percutaneous endovascular coiling and appropriate medical management. This case highlights that clinical suspicion, prompt diagnosis and urgent intervention with a multidisciplinary approach can help successfully manage a vascular insult.


Recovery of value-added products by mining microalgae.
Microalgae blooms are always blamed for the interruption of the aquatic environment and pose a risk to the source of drinking water. Meanwhile, microalgae as primary producers are a kind of resource pool and could benefit the environment and contribute to building a circular economy. The lipid and polyhydroxybutyrate (PHB) in the cells of microalgae could be alternatives to fossil fuels and plastics, respectively, which are the culprits of global warming and plastic pollution. Besides, some microalgae are rich in nutrients, such as proteins and astaxanthin, which make themselves suitable for feed additives. As wastewater is rich in nutrients necessary for microalgae, thus, value-added product recovery via microalgae could be an approach to valorizing wastewater. However, a one-size-fits-all approach deploying various wastewater for the above products cannot be summarized. On the contrary, specific technical protocols should be tailored regarding each product in microalgae biomass with various wastewater. Thus, this review is to summarize the research effort by far on wastewater-cultivated microalgae for value-added products. Wastewater type, regulation methods, and targeted product yields are compiled and discussed and are expected to guide future extrapolation into a commercial scale.


FAD-dependent C-glycoside-metabolizing enzymes in microorganisms: Screening, characterization, and crystal structure analysis.
C-glycosides have a unique structure, in which an anomeric carbon of a sugar is directly bonded to the carbon of an aglycone skeleton. One of the natural C-glycosides, carminic acid, is utilized by the food, cosmetic, and pharmaceutical industries, for a total of more than 200 tons/y worldwide. However, a metabolic pathway of carminic acid has never been identified. In this study, we isolated the previously unknown carminic acid-catabolizing microorganism and discovered a flavoenzyme "C-glycoside 3-oxidase" named CarA that catalyzes oxidation of the sugar moiety of carminic acid. A Basic Local Alignment Search Tool (BLAST) search demonstrated that CarA homologs were distributed in soil microorganisms but not intestinal ones. In addition to CarA, two CarA homologs were cloned and heterologously expressed, and their biochemical properties were determined. Furthermore, a crystal structure of one homolog was determined. Together with the biochemical analysis, the crystal structure and a mutagenesis analysis of CarA revealed the mechanisms underlying their substrate specificity and catalytic reaction. Our study suggests that CarA and its homologs play a crucial role in the metabolism of C-glycosides in nature.


Cardiovascular events and the role of accelerated atherosclerosis in systemic vasculitis.
The spectrum of inflammatory blood vessel diseases includes both atherosclerosis and the primary systemic vasculitides. Although the inciting triggers differ, significant overlap exists in the mechanisms that contribute to sustained inflammation and vascular damage in both entities. With improvement in therapeutics to control acute vasculitis leading to longer survival, cardiovascular morbidity and mortality has emerged as the leading cause of death for vasculitis patients. Cardiovascular events likely occur as a consequence of vasculitis, vascular damage from prior inflammation causing a sustained procoagulant state, and accelerated atherosclerosis. In this review, we discuss the latest evidence regarding risk of cardiovascular events in patients with major forms of primary systemic vasculitis, and review the mechanisms by which accelerated atherosclerosis may occur.


MAIT cells regulate NK cell-mediated tumor immunity.
The function of MR1-restricted mucosal-associated invariant T (MAIT) cells in tumor immunity is unclear. Here we show that MAIT cell-deficient mice have enhanced NK cell-dependent control of metastatic B16F10 tumor growth relative to control mice. Analyses of this interplay in human tumor samples reveal that high expression of a MAIT cell gene signature negatively impacts the prognostic significance of NK cells. Paradoxically, pre-pulsing tumors with MAIT cell antigens, or activating MAIT cells in vivo, enhances anti-tumor immunity in B16F10 and E0771 mouse tumor models, including in the context of established metastasis. These effects are associated with enhanced NK cell responses and increased expression of both IFN-γ-dependent and inflammatory genes in NK cells. Importantly, activated human MAIT cells also promote the function of NK cells isolated from patient tumor samples. Our results thus describe an activation-dependent, MAIT cell-mediated regulation of NK cells, and suggest a potential therapeutic avenue for cancer treatment.


Responses of phytoplankton community structure and association to variability in environmental drivers in a tropical coastal lagoon.
Spatial and seasonal heterogeneity in phytoplankton communities are governed by many biotic and abiotic drivers. However, the identification of long-term spatial and temporal trends in abiotic drivers, and their interdependencies with the phytoplankton communities' structure is understudied in tropical brackish coastal lagoons. We examined phytoplankton communities' spatiotemporal dynamics from a 5-year dataset (n = 780) collected from 13 sampling stations in Chilika Lagoon, India, where the salinity gradient defined the spatial patterns in environmental variables. Generalized additive models showed a declining trend in phytoplankton biomass, pH, and dissolved PO4 in the lagoon. Hierarchical modelling of species communities revealed that salinity (44.48 ± 28.19%), water temperature (4.37 ± 5.65%), and season (4.27 ± 0.96%) accounted for maximum variation in the phytoplankton composition. Bacillariophyta (Indicator Value (IV): 0.74) and Dinophyta (IV: 0.72) emerged as top indicators for polyhaline regime whereas, Cyanophyta (IV: 0.81), Euglenophyta (IV: 0.79), and Chlorophyta (IV: 0.75) were strong indicators for oligohaline regime. The responses of Dinophyta and Chrysophyta to environmental drivers were much more complex as random effects accounted for ~70-75% variation in their abundances. Prorocentrum minimum (IV: 0.52), Gonyaulax sp. (IV: 0.52), and Alexandrium sp. (IV: 0.51) were potential indicators of P-limitation. Diploneis weissflogii (IV: 0.43), a marine diatom, emerged as a potential indicator of N-limitation. Hierarchical modelling revealed the positive association between Cyanophyta, Chlorophyta, and Euglenophyta whereas, Dinophyta and Chrysophyta showed a negative association with Cyanophyta, Chlorophyta, and Euglenophyta. Landsat 8-Operational Land Imager satellite models predicted the highest and lowest Cyanophyta abundances in northern and southern sectors, respectively, which were in accordance with the near-coincident field-based measurements from the lagoon. This study highlighted the dynamics of phytoplankton communities and their relationships with environmental drivers by separating the signals of habitat filtering and biotic interactions in a monsoon-regulated tropical coastal lagoon.


Therapeutic apheresis during pregnancy: A single center experience.
Therapeutic apheresis (TA) represents a treatment option for pre-existing conditions or diseases occurring during gestation. Although pregnancy is not a contraindication per se, due to the lack of evidence-based guidelines and presumed risk of maternal/fetal adverse events there is a general resistance to its application. Between January 2005 and August 2017, at the Apheresis Unit of the University Hospital of Padua 936 TA procedures were performed during 57 pregnancies in 48 patients: 813 Plasma Exchange sessions, 119 Immunoadsorptions, 4 Red Blood Cell exchanges. The treated disease were as follows: antiphospholipid syndrome (18 patients), autoimmune congenital heart block (18), myasthenia gravis (3), Rh alloimmunization (2), systemic sclerosis (1), suspected autoimmune encephalitis (1), severe hypertriglyceridaemia (1), post partum hemolytic-uremic syndrome (1), sickle cell disease (1), lupus nephritis (1) and thrombotic thrombocytopenic purpura (1). In the time period considered the apheresis sessions applied to pregnant women were 7.1% of the total (n = 13.251). The median age at the first treatment was 33 years. The median week of gestation (WG) at the beginning of treatments was 21. Twenty (2.1%) sessions were complicated by adverse events, none requiring or prolonging hospitalization. There were 50 live births, 5 spontaneous abortions and 2 voluntary terminations of pregnancy. Median WG at delivery was 35 and caesarean section was performed in 46 cases. Our data showed that TA in pregnancy is well tolerated. Close collaboration between clinician, obstetrician and TA specialist is crucial to ensure a good outcome of high-risk pregnancies.


miR-138-5p inhibits proliferation and invasion in kidney renal clear cell carcinoma by targeting SINA3 and regulation of the Notch signaling pathway.
The function of miR-138-5p as an oncogenic factor has been reported in certain cancers. This study was performed to analyze the potential involvement of miR-138-5p in kidney renal clear cell carcinoma (KIRC). The Cancer Genome Atlas (TCGA) database was used to explain the expression of miR-138-5p in cancer and paired non-cancer tissues of KIRC patients. Subsequently, miR-138-5p expression in KIRC tissues and cell lines, as well as that in normal tissues and normal renal tubular epithelial cell line, was detected. Artificial overexpressing of miR-138-5p was applied to observe its effect on the biological behaviors of KIRC cells. The target mRNA of miR-138-5p, SIN3A, was predicted and validated. Altered expression of miR-138-5p and SIN3A was introduced to confirm their functions in KIRC proliferation and invasion. We showed that miR-138-5p was down-regulated in tumor tissues of KIRC patients comparing to adjacent healthy tissues and linked to dismal prognosis in patients. miR-138-5p could hinder KIRC proliferation and invasion, while artificial overexpression of SIN3A led to reversed trends. SIN3A was a target mRNA of miR-138-5p. miR-138-5p and SIN3A together affect the activation of the Notch signaling pathway. This study evidenced that up-regulated miR-138-5p inhibits proliferation and invasion of KIRC cells involving the transcription of SIN3A and the following regulation of the Notch signaling pathway.


Affinity purification of Candida albicans CaCdc4-associated proteins reveals the presence of novel proteins involved in morphogenesis.
Candida albicans CDC4 is nonessential and plays a role in suppressing filamentous growth, in contrast to its evolutionary counterparts involved in the G1-S transition of the cell cycle. Genetic epistasis analysis has indicated that proteins besides Sol1 are targets of C. albicans Cdc4. Moreover, no formal evidence suggests that C. albicans Cdc4 functions through the ubiquitin E3 ligase of the Skp1-Cul1/Cdc53-F-box complex. To elucidate the role of C. albicans CDC4, C. albicans Cdc4-associated proteins were sought by affinity purification. A 6xHis epitope-tagged C. albicans Cdc4 expressed from Escherichia coli was used in affinity purifications with the cell lysate of C. albicans cdc4 homozygous null mutant. Candida albicans Cdc4 and its associated proteins were resolved by SDS-PAGE and visualized by silver staining. The candidate proteins were recovered and trypsin-digested to generate MALDI-TOF spectra profiles, which were used to search against those of known proteins in the database to reveal their identities. Two out of four proteins encoded by GPH1 and THR1 genes were further verified to interact with C. albicans Cdc4 using a yeast two-hybrid assay. We conclude that in vitro affinity purification using C. albicans Cdc4 generated from E. coli as the bait and proteins from cell lysate of C. albicans cdc4 homozygous null mutant as a source of prey permit the identification of novel proteins that physically interact and functionally associate with C. albicans Cdc4.


Phosphoinositides provide a regulatory mechanism of surface charge and active transport.
Yeast cells, when grown in the presence of arsenate, are capable of accumulating phosphoinositides (PI) at the expense of inhibiting their degradation more than their synthesis. PI levels return to normal when the cells are cultured or exposed to media without arsenate. These reversible changes are employed as a tool to test the effect of inositide accumulation and dynamics on several membrane properties. In the PI-rich cells, phosphate and arsenate transport from low external concentrations (high affinity systems), as well as the transport of glycine, which enter the cells accompanied by protons, were increased. The proton ejection energized by glucose is also enhanced in the PI-rich cells that show a more efficient potassium inflow at pH 4.0-4.5. The membrane surface potential of the PI-rich cells was found to be 2-times higher than that of the normal cells, in agreement with the 2-fold increment in the PI. All the above mentioned alterations in membrane properties are reverted when the PI content of the PI-rich cells is reduced to the level of normal cells. The results show the participation of the phosphoinositides in the formation, maintenance and regulation of the membrane surface potential and their possible influence upon transport mechanisms.


Identification of stool proteins in C57BL/6J mice by two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry.
Gastrointestinal disease is a major cause of mortality in humans and animals, and the detection of disease-associated protein in stool is an established diagnostic method in this context. Yet, no data currently exists about the protein composition of mammalian faeces. Using a newly developed two-dimensional (2D) gel method, 28 of the most abundant proteins in murine faeces were identified. Mammalian faeces contains protein from multiple species (from the individual, from gastrointestinal bacteria, from food, etc.). Yet, it was found that the majority of mouse stool proteins were of mouse origin, with a minority of proteins being derived from food (in particular soybean glycinin and conglycinin) and bacteria (flagellin). Most mouse proteins were proteases and saccharidases derived from the exocrine pancreas. In addition, two unexpected mouse proteins were identified: one was a newly described mucin-like protein from intestinal goblet cells (FcgammaBP); the other was the secreted form of carbonic anhydrase (type VI) from salivary gland. The data suggest that 2D analysis of faecal protein is likely to provide meaningful information about the physiological stage of the gastrointestinal tract. Compared with studies based on biopsies, faecal protein analysis may reduce the number of laboratory animals, and might also allow quicker bridging from animal studies to humans, where biopsy material is more difficult to obtain and is less relevant for general practice use.


Modified Nuss procedure for the treatment of pectus excavatum: Experience of 259 patients.
Pectus excavatum is not rare in China. Many treatments for this disease have proved to have many shortcomings. Nuss procedure has been a ground-breaking technology, but it also has some disadvantages. Hence, this study was conducted to review our experience in the use of modified Nuss procedure in our hospital. Data from 259 patients suffered from pectus excavatum between August 2020 and August 2021 who were treated with modified Nuss procedure was analyzed retrospectively. Age was from 3 to 37 years. The average was 15.54 years. The male was 213 cases and the female was 46 cases. The time patients or their family members found pectus excavatum varied. 10 cases had been repaired previously when patients were admitted in our hospital. The clinical symptoms also varied. Each case had an improvement in Haller index. The average of the postoperative hospitalization was 3.97 days. Most cases were inserted 1 bar. Complication rate was also very low. All patients or their parents or their guardians were satisfied with the appearance of the chest wall after operation. There was no death in the whole observation period. From our experience, this modified Nuss procedure have obtained optimistic outcomes with more minimal invasion and low complication rate. This surgical method may be applied to many other hospitals in the future.


Muscle mitochondrial energetics predicts mobility decline in well-functioning older adults: The baltimore longitudinal study of aging.
Muscle mitochondrial dysfunction is associated with poor mobility in aging. Whether mitochondrial dysfunction predicts subsequent mobility decline is unknown. We examined 380 cognitively normal participants aged 60 and older (53%women, 22%Black) who were well-functioning (gait speed ≥ 1.0 m/s) and free of Parkinson's disease and stroke at baseline and had data on baseline skeletal muscle oxidative capacity and one or more mobility assessments during an average 2.5 years. Muscle oxidative capacity was measured by phosphorus magnetic resonance spectroscopy as the post-exercise recovery rate of phosphocreatine (kPCr ). Mobility was measured by four walking tests. Associations of baseline kPCr with mobility changes were examined using linear mixed-effects models, adjusted for covariates. In a subset, we examined whether changes in muscle strength and mass affected these associations by adjusting for longitudinal muscle strength, lean mass, and fat mass. Lower baseline kPCr was associated with greater decline in all four mobility measures (β, p-value: (0.036, 0.020) 6-m usual gait speed; (0.029, 0.038) 2.5-min usual gait speed; (0.034, 0.011) 6-m rapid gait speed; (-0.042, <0.001) 400-m time). In the subset, further adjustment for longitudinal muscle strength, lean mass, and fat mass attenuated longitudinal associations with changes in mobility (Δβ reduced 26-63%). Among initially well-functioning older adults, worse muscle mitochondrial function predicts mobility decline, and part of this longitudinal association is explained by decline in muscle strength and mass. Our findings suggest that worse mitochondrial function contributes to mobility decline with aging. These findings need to be verified in studies correlating longitudinal changes in mitochondrial function, muscle, and mobility performance.


Augmented prenatal auditory stimulation alters postnatal perception, arousal, and survival in bobwhite quail chicks.
This study examined whether previously reported effects of altered prenatal sensory experience on subsequent acceleration of intersensory development in precocial birds are mediated by mechanisms sensitive to the overall amount of stimulation provided. Results revealed that bobwhite quail chicks exposed to substantially augmented amounts of prenatal auditory stimulation show altered patterns of species-typical perceptual development. Specifically, chicks continued to respond to maternal auditory cues into later stages of postnatal development and failed to demonstrate responsiveness to maternal visual cues. In addition, embryos exposed to substantially augmented amounts of prenatal auditory stimulation exhibited a higher level of behavioral arousal and higher mortality rates than embryos provided either moderately augmented amounts or no additional amount of prenatal auditory stimulation. These findings suggest that substantially increased amounts of prenatal sensory stimulation can interfere with the emergence of species-typical patterns of postnatal perceptual functioning and lend support to the notion that sensory stimulation that falls within some optimal range maintains or facilitates normal patterns of perceptual development, whereas stimulation beyond the range of the species norm can result in intersensory and intersensory interference.


Teaching Effective Informed Consent Communication Skills in the Virtual Surgical Clerkship.
The disruption by the COVID-19 pandemic on undergraduate medical education allowed for assessment of virtual curricular innovations. One of the difficulties encountered in the virtual curriculum is the teaching of clinical competencies that would traditionally require students to undergo in-person simulations and patient encounters. We implemented a novel informed consent activity module, with standardized patients, to improve self-efficacy in communication within our core surgery clerkship. All medical students who participated in the virtual surgery clerkship were recruited to participate in a retrospective survey study regarding the novel informed consent module. These questions evaluated their perceived competence in 4 domains relating to informed consent: identifying the key elements, describing common challenges, applying the New Mexico Clinical Communication Scale (NMCCS), and documenting. Thirty-four of 90 students participated in the study (38% of the cohort). Respondents to the survey reported that their self-efficacy in communication skills related to informed consent improved as a result of their participation in the activity in each of the 4 domains surveyed (p < 0.01), with the majority of students identifying as satisfactory or above in each domain post-module. Students generally viewed the virtual informed consent activity positively, but noted that it was not the same as an in-person clinical experience. A virtual module of communication skills training, using standardized patients and faculty, improved students' belief in their self-efficacy in obtaining informed consent. This communication module can be useful in a virtual or mixed curricular structure for both current and future medical students.


The first multiplication atom-bond connectivity index of molecular structures in drugs.
In the field of medicine, there are a large number of new drugs synthesis every year. Before entering the clinical stage, it needs a lot of work on drug testing of the various properties. Due to the lack of a large number of laboratory technician, laboratory equipment and reagents, the drug testing of many biochemical properties are not completed. Theoretical medicine provides a theoretical way for medical researchers to obtain the pharmaceutical properties of compounds by calculation tricks. In this paper, the first multiplication atom-bond connectivity index of several common drugs structure are studied, and the accurate expressions are determined. These theoretical conclusions provide practical guiding significance for pharmaceutical engineering.


Comparing the significance of the utilization of next generation and third generation sequencing technologies in microbial metagenomics.
Since the exploration of sequencing began in 2005, third and next-generation sequencing (TGS and NGS) technologies have fundamentally changed metagenomics research. These platforms provide essential benefits regarding speed, cost, quality and precision in the never-ending search for microorganisms' genetic material, regardless of location on earth. TGS are typically represented by technologies driven from power generation by semiconductor chips and utilization of enzymatic reactions by SOLiD/Ion Torrent PGM™ from Life Sciences, sequencing by synthesis using fluorescent labels on HiSeq/MiSeq™ from Illumina, pyrosequencing by GS FLX Titanium/GS Junior from Roche and nanopore-based sequencing by MinION™/GridION™/PromethION™ from Oxford Nanopore Technologies. The evolution of this technology enabled researchers to continually broaden their knowledge of the microbial world. This review presents a comprehensive overview of the recent literature on the utilization of both TGS and NGS technologies for the investigation of microbial metagenomics, their benefits and limitations with real-time examples of novel applications in clinical microbiology and public health, food and agriculture, energy and environment, arts and space.


Structural mechanisms of RNA recognition: sequence-specific and non-specific RNA-binding proteins and the Cas9-RNA-DNA complex.
RNA-binding proteins play crucial roles in RNA processing and function as regulators of gene expression. Recent studies have defined the structural basis for RNA recognition by diverse RNA-binding motifs. While many RNA-binding proteins recognize RNA sequence non-specifically by associating with 5' or 3' RNA ends, sequence-specific recognition by RNA-binding proteins is typically achieved by combining multiple modular domains to form complex binding surfaces. In this review, we present examples of structures from different classes of RNA-binding proteins, identify the mechanisms utilized by them to target specific RNAs, and describe structural principles of how protein-protein interactions affect RNA recognition specificity. We also highlight the structural mechanism of sequence-dependent and -independent interactions in the Cas9-RNA-DNA complex.


The psychiatric halfway house: how is it measuring up?
To obtain data on the effectiveness of the psychiatric halfway house and to update information about such facilities, 26 recent statistical reports were examined. Only two studies include control group comparisons. In addition to descriptive information, data are reported in terms of employment or school attendance and independent living as contrasted with rehospitalization. Results indicate that a median of approximately 80 per cent of halfway house residents adjusts to community living. Despite differences among halfway houses in resident selection, length of stay, rehabilitative criteria, and nature of follow-up, data suggest that rehospitalization rates are lower after residence in a halfway house. Some cautions are drawn regarding evaluative studies and potential attenuation of halfway house facilities to low-quality custodial care.


Left hemicolectomy with rectal excision for severe idiopathic constipation.
The standard surgical therapy for severe idiopathic constipation is total colectomy with ileorectal anastomosis, but this results in intractable diarrhoea in a third of the patients and recurrent constipation in another 10%. Studies which employ either radio-isotopes or radio-opaque markers permit the delineation of regional delay in colonic transit. Based on these studies, and evidence that the rectum is also abnormal in these patients, we have performed a left hemicolectomy with rectal excision in 2 patients with proven left colonic delay. After 2 and 3 years of follow-up, both patients have normal frequency, transit studies and anorectal physiology studies. Segmental resection based on physiological studies may offer better relief of symptoms with a lower chance of side effects in selected patients.


Relationship between post-stroke dysphagia and pharyngeal sensory impairment.
Post-stroke dysphagia (PSD) is common and can lead to serious complications. Pharyngeal sensory impairment is assumed to contribute to PSD. The aim of this study was to investigate the relationship between PSD and pharyngeal hypesthesia and to compare different assessment methods for pharyngeal sensation. In this prospective observational study, fifty-seven stroke patients were examined in the acute stage of the disease using Flexible Endoscopic Evaluation of Swallowing (FEES). The Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) and impaired secretion management according to the Murray-Secretion Scale were determined, as well as premature bolus spillage, pharyngeal residue and delayed or absent swallowing reflex. A multimodal sensory assessment was performed, including touch-technique and a previously established FEES-based swallowing provocation test with different volumes of liquid to determine the latency of swallowing response (FEES-LSR-Test). Predictors of FEDSS, Murray-Secretion Scale, premature bolus spillage, pharyngeal residue, and delayed or absent swallowing reflex were examined with ordinal logistic regression analyses. Sensory impairment using the touch-technique and the FEES-LSR-Test were independent predictors of higher FEDSS, Murray-Secretion Scale, and delayed or absent swallowing reflex. Decreased sensitivity according to the touch-technique correlated with the FEES-LSR-Test at 0.3 ml and 0.4 ml, but not at 0.2 ml and 0.5 ml trigger volumes. Pharyngeal hypesthesia is a crucial factor in the development of PSD, leading to impaired secretion management and delayed or absent swallowing reflex. It can be investigated using both the touch-technique and the FEES-LSR-Test. In the latter procedure, trigger volumes of 0.4 ml are particularly suitable.


High levels of protein expression using different mammalian CMV promoters in several cell lines.
With the recent completion of the human genome sequencing project, scientists are faced with the daunting challenge of deciphering the function of these newly found genes quickly and efficiently. Equally as important is to produce milligram quantities of the therapeutically relevant gene products as quickly as possible. Mammalian expression systems provide many advantages to aid in this task. Mammalian cell lines have the capacity for proper post-translational modifications including proper protein folding and glycosylation. In response to the needs described above, we investigated the protein expression levels driven by the human CMV in the presence or absence of intron A, the mouse and rat CMV promoters with intron A, and the MPSV promoter in plasmid expression vectors. We evaluated the different promoters using an in-house plasmid vector backbone. The protein expression levels of four genes of interest driven by these promoters were evaluated in HEK293EBNA and CHO-K1 cells. Stable and transient transfected cells were utilized. In general, the full-length human CMV, in the presence of intron A, gave the highest levels of protein expression in transient transfections in both cell lines. However, the MPSV promoter resulted in the highest levels of stable protein expression in CHO-K1 cells. Using the CMV driven constitutive promoters in the presence of intron A, we have been able to generate >10 microg/ml of recombinant protein using transient transfections.


Cytogenetic low-dose hyperradiosensitivity is observed in human peripheral blood lymphocytes.
The shape of the ionizing radiation response curve at very low doses has been the subject of considerable debate. Linear-no-threshold (LNT) models are widely used to estimate risks associated with low-dose exposures. However, the low-dose hyperradiosensitivity (HRS) phenomenon, in which cells are especially sensitive at low doses but then show increased radioresistance at higher doses, provides evidence of nonlinearity in the low-dose region. HRS is more prominent in the G2 phase of the cell cycle than in the G0/G1 or S phases. Here we provide the first cytogenetic mechanistic evidence of low-dose HRS in human peripheral blood lymphocytes using structural chromosomal aberrations. Human peripheral blood lymphocytes from 2 normal healthy female donors were acutely exposed to cobalt 60 γ rays in either G0 or G2 using closely spaced doses ranging from 0 to 1.5 Gy. Structural chromosomal aberrations were enumerated, and the slopes of the regression lines at low doses (0-0.4 Gy) were compared with doses of 0.5 Gy and above. HRS was clearly evident in both donors for cells irradiated in G2. No HRS was observed in cells irradiated in G0. The radiation effect per unit dose was 2.5- to 3.5-fold higher for doses ≤0.4 Gy than for doses >0.5 Gy. These data provide the first cytogenetic evidence for the existence of HRS in human cells irradiated in G2 and suggest that LNT models may not always be optimal for making radiation risk assessments at low doses.


Introduction: circadian rhythm and its disruption: impact on reproductive function.
Almost all forms of life have predictable daily or circadian rhythms in molecular, endocrine, and behavioral functions. In mammals, a central pacemaker located in the suprachiasmatic nuclei coordinates the timing of these rhythms. Daily light exposure that affects the retina of the eye directly influences this area, which is required to align endogenous processes to the appropriate time of day. The present "Views and Reviews" articles discuss the influence of circadian rhythms, especially nightly secretion of melatonin, on reproductive function and parturition. In addition, an examination is made of problems that arise from recurrent circadian rhythm disruption associated with changes in light exposure patterns common to modern day society. Finally, a possible solution to prevent disruptions in circadian phase markers by filtering out short wavelengths from nocturnal light is reviewed.


Blisters on your fingers.
Mesenchymal progenitor cells play a key role in fibrogenesis. An exciting paper was recently published showed that blister fluid from the skin patients with the autoimmune connective tissue disease scleroderma (systemic sclerosis, SSc) preferentially activated mesenchymal progenitor cells (Taki et al. in Arthritis Rheumatol 72(8):1361-1374, 2020). These data provide new and invaluable insights into the complex interactions in the connective tissue microenvironment that ultimately result in persistent, pathological fibrosis.


Biomechanical aspects on overdenture treatment.
Implant retained overdentures utilize a wide range of attachments to provide the retentive forces for implant retained overdentures. Such attachments attempt to minimize the functional stresses at the implant-overdenture interfaces. Clinical experiments with strain gauges can monitor the types and magnitudes of deformation that appear in the underlying surfaces. Clinical results have shown that fixed and removable prostheses perform differently in type, magnitude and direction of the applied load from laboratory tests. There is good correlation between short term clinical experiments and long term clinical follow-ups of prosthesis provision. Removable prosthetic superstructures perform at a lower level of overall functional rigidity with increased risk of deformation. Factors that influence the loading patterns and surface straining are the incorporation of an internal metal frame, the rheological properties of the foodstuff, the occlusal position of the teeth and the degree of fit of the prosthetic suprastructure and the implants. The prognosis of implant retained overdentures is maximized when the number of fixtures used is high, a rigid bar design is used and functional flexibility is incorporated in the prosthesis design.


MiR-133a-3p attenuates resistance of non-small cell lung cancer cells to gefitinib by targeting SPAG5.
Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), clinically used to treat patients with non-small cell lung cancer driven by EGFR mutations. Unfortunately, EGFR-TKI resistance has become a clinical problem for the effective treatment of NSCLC patients. The purpose of this study was to explore the effect and mechanism of miR-133a-3p on the gefitinib sensitivity of NSCLC cells. The gefitinib-resistant PC9 (PC9/GR) cells were established through repeated long-term exposure to gefitinib for half a year. Then, PC9/GR cells were transfected with miR-133a-3p mimics and PC9 cells were transfected with miR-133a-3p inhibitors to increase or decrease the expression of miR-133a-3p. CCK-8 assay, colony formation assay, and caspase-3 activity assay were employed to detect cell resistance to gefitinib. Quantitative real-time PCR and Western blotting were used to evaluate the levels of miR-133a-3p, SPAG5, and other related genes. Starbase database was used to predict the target gene of miR-133a-3p and the prognosis of NSCLC patients. Target gene of miR-133a-3p was verified through dual-luciferase reporter gene assay. MiR-133a-3p was significantly downregulated in gefitinib-resistant cell line PC9/GR vs. gefitinib-sensitive cell line PC9. Overexpression of miR-133a-3p increased the sensitivity of NSCLC cells to gefitinib and vice versa. Furthermore, SPAG5 is an important target gene of miR-133a-3p, and SPAG5 can reverse miR-133a-3p-mediated gefitinib sensitivity of NSCLC cells. These findings indicated that miR-133a-3p/SPAG5 axis played a vital role in acquired resistance to gefitinib in NSCLC cells, and miR-133a-3p may represent a potential therapeutic strategy for the treatment of human NSCLC.


Importance of NOD2/CARD15 gene variants for susceptibility to and outcome of sepsis in Turkish children.
Severe sepsis remains a leading cause of morbidity and mortality in children. Given the link to pathogenesis, polymorphisms in genes involved in infection and inflammation may influence the outcomes in patients with sepsis and septic shock. The role of mutations within the innate immunity receptor NOD2/CARD15 has recently been demonstrated as a risk factor for bacteremia and mortality in adult patients with sepsis. The aim of this study was to evaluate the role of mutations of the NOD2/CARD15 gene in pediatric patients with sepsis. Prospective cohort study. A tertiary care, ten-bed, pediatric intensive care unit. One hundred twenty-eight patients with sepsis admitted to the pediatric intensive care unit and healthy control group were included. Venous blood from the children with sepsis and healthy controls was collected to investigate common polymorphisms (Arg702Trp, Gly908Arg, Leu1007fsincC) within the NOD2/CARD15 gene. Standard polymerase chain reaction restriction fragment length polymorphism technique was used to determine NOD2/CARD15 gene polymorphism. R702W, G908R, and Leu1007fsinsC variants in the NOD2/CARD15 gene were determined as significant risk factors associated with susceptibility to sepsis (p = .025, p = .031, p = .014, respectively). Sepsis-related mortality was increased in children carrying the Leu1007fsinsC variant (p = .041). The present article is the first report of clinical implications of NOD2/CARD15 gene variants in children with sepsis. Our findings suggest that common polymorphisms in the NOD2/CARD15 gene may play a major role in susceptibility to sepsis and the outcome of sepsis in children.


Morphometric analysis of experimental spinal cord injury in the cat: the relation of injury intensity to survival of myelinated axons.
The pattern of axonal destruction and demyelination that occurs in experimental contusion injury of cat thoracic spinal cord was studied by line sampling of axons in 1 micron thick plastic sections with the light microscope. Injuries were produced by a weight-drop apparatus, with the vertebral body (T9) below the impact stabilized by supports under the transverse processes. The effects of two combinations of weight and height were examined: 10 or 13 g dropped 20 cm onto an impact area of 5 mm diameter. Animals were kept for 3-5 months after injury, then fixed by perfusion for histological analysis. The number of surviving myelinated axons was found to vary both with the weight used and with the size of the spinal cord. A measure of impact intensity was derived from the calculated momentum of the weight at impact divided by the cross sectional area of the cord (interpolated from dimensions measured rostral and caudal of the lesion following fixation). At impact intensities greater than 0.02 kg-m/s/cm2 there was practically no survival of axons at the center of the injury site, combined with almost complete breakdown of the pial margin. Between 0.08 and 0.2 kg-m/s/cm2 the number of surviving axons varied between 100,000 and 2,000, approximating a negative exponential function (r = -0.88). The number of axons surviving in the outer 100 microns of the cord varied practically linearly (r = -0.82) between near normal and less than 1% of normal over the same range of injury intensity. The number of surviving axons decreased with depth from the pia, also approximating a negative exponential function, with a 10-fold decrease in density over approximately 500 microns. The average slope of this relation with depth remained similar over the range of injury intensity examined, though the slope appeared inversely related to variation in axonal survival for different individuals at a given intensity. It is argued that the loss of axons is probably determined primarily by mechanical stretch at the time of impact. Its centrifugal pattern may be explained by longitudinal displacement of the central contents of the cord, reflecting the viscoelastic "boundary layer" properties of parenchymal flow within the meningeal tube. This is illustrated with reference to the behavior of a gelatin model under compression. The preferential loss of large caliber axons and the characteristic shift to abnormally thin myelin sheaths (resulting from post-traumatic demyelination) both varied in extent independently of injury intensity and overall axonal survival.(ABSTRACT TRUNCATED AT 400 WORDS)


The rainbow trout (Oncorhynchus mykiss) interferon response in the ovary.
Immune responses in the ovary are tightly regulated to provide protection for the developing germ cells, which are very sensitive to inflammatory responses. This characteristic immune response is often used by viral pathogens to evade the immune system, replicate and be transmitted to other specimens through the ovary. Taking into account that in teleost fish, the innate immune system is considered crucial to the outcome of viral infections and the interferon (IFN) system is considered as the first line of defence against viruses, we have studied the IFN response in rainbow trout (Oncorhynchus mykiss) ovary using two viruses with different replicative capacity in this organ, namely viral haemorrhagic septicaemia virus (VHSV) and infectious pancreatic necrosis virus (IPNV). Both VHSV and IPNV are shed from the ovary, but while VHSV actively replicates at this site, IPNV remains silent. In this context, we have determined the levels of expression of IFNs and the IFN-induced Mx genes in the ovary upon in vivo and in vitro infections with VHSV and IPNV, and compared to the effects provoked by the viral mimic poly I:C in vivo. We have demonstrated that while VHSV strongly up-regulates all the IFN genes studied, IPNV in vivo exposure either has no effect or even provokes strong suppression of IFN gene expression. These differences are not observed in vitro, even though IPNV does not replicate actively in this case either. Finally, to better understand the role that the production of type I IFN plays in the ovary, we have studied the effects of two type I recombinant rainbow trout IFNs (rtIFN1 and rtIFN2) to modulate both the expression of immune genes and to establish an antiviral state in the ovary. Interestingly, the ovary was able to respond to both rtIFN1 and 2, despite the fact that the IFN1 gene was not expressed here. Moreover, rtIFN1 and rtIFN2 not only modulated the expression of genes related to the IFN response, but also modulated inflammatory genes and significantly suppressed VHSV replication.


Differentiation between benign and malignant vertebral compression fractures using qualitative and quantitative analysis of a single fast spin echo T2-weighted Dixon sequence.
To determine and compare the qualitative and quantitative diagnostic performance of a single sagittal fast spin echo (FSE) T2-weighted Dixon sequence in differentiating benign and malignant vertebral compression fractures (VCF), using multiple readers and different quantitative methods. From July 2014 to June 2020, 95 consecutive patients with spine MRI performed prior to cementoplasty for acute VCFs were retrospectively included. VCFs were categorized as benign (n = 63, mean age = 76 ± 12 years) or malignant (n = 32, mean age = 63 ± 12 years) with a best valuable comparator as a reference. Qualitative analysis was independently performed by four radiologists by categorizing each VCF as either benign or malignant using only the image sets provided by FSE T2-weighted Dixon sequences. Quantitative analysis was performed using two different regions of interest (ROI1-2) and three methods (signal drop, fat fraction (FF) from ROIs, FF maps). Diagnostic performance was compared using ROC curves analyses. Interobserver agreement was assessed using kappa statistics and intraclass correlation coefficients (ICC). The qualitative diagnostic performance ranged from area under the curve (AUC) = 0.97 (95% CI: 0.91-1.00) to AUC = 0.99 (95% CI: 0.95-1.0). The quantitative diagnostic performance ranged from AUC = 0.82 (95% CI: 0.73-0.89) to AUC = 0.97 (95% CI: 0.91-0.99). Pairwise comparisons showed no statistical difference in diagnostic performance (all p > 0.0013, Bonferroni-corrected p < 0.0011). All five cases with disagreement among the readers were correctly diagnosed at quantitative analysis using ROI2. Interobserver agreement was excellent for both qualitative and quantitative analyses. A single FSE T2-weighted Dixon sequence can be used to differentiate benign and malignant VCF with high diagnostic performance using both qualitative and quantitative analyses, which can provide complementary information. • Qualitative analysis of a single FSE T2-weighted Dixon sequence yields high diagnostic performance and excellent observer agreement for differentiating benign and malignant compression fractures. • The same FSE T2-weighted Dixon sequence allows quantitative assessment with high diagnostic performance. • Quantitative data can readily be extracted from the FSE T2-weighted Dixon sequence and may provide complementary information to the qualitative analysis, which may be useful in doubtful cases.


High Complication Rate After Percutaneous Screw Fixation for Valgus-Impacted Femoral Neck Fractures Without Sagittal Malalignment.
To evaluate the rate of reoperation in patients without sagittal plane malalignment who underwent percutaneous screw fixation of a valgus-impacted femoral neck fracture. Retrospective case series. Two Level 1 academic trauma centers. Two hundred seven patients >50 years of age with valgus-impacted femoral neck fractures treated with at least 3 large-diameter (>6.5 mm) cancellous screws from 2013 to 2019. Patients were excluded if there was a sagittal plane fracture deformity. The primary outcome was reoperation. Secondary outcomes considered "major complications" included: avascular necrosis, varus collapse or implant cutout, nonunion, deep infection, and hematoma requiring reoperation. Surgical fixation strategies (screw configuration, aim) and implant type (partial vs. fully threaded cancellous screws) were secondarily compared. Average patient age was 77 years, and median clinical follow-up was 658 days. Thirty-one patients (15%) required reoperation, and the major complication rate was 17.3% (36 complications in 33 patients). Logistic regression analysis demonstrated a higher risk of reoperation with constructs consisting of all partially threaded screws (17.0%) compared with the use of at least 1 fully threaded screw (7.5%) when an inverted triangle configuration was used (odds ratio, 2.50; 95% CI, 0.81-7.77). This study demonstrated a relatively high rate of reoperation and major complications in patients with valgus-impacted femoral neck fractures without sagittal malalignment treated with in situ percutaneous screw fixation. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Wnt-β Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis and Dysfunction of the External Anal Sphincter.
Wnt-β catenin is an important signaling pathway in the genesis of fibrosis in many organ systems. Our goal was to examine the role of Wnt pathway in the external anal sphincter (EAS) injury-related fibrosis and muscle dysfunction. New Zealand White female rabbits were subjected to surgical EAS myotomy and administered local injections of either a Wnt antagonist (sFRP-2; daily for 7 days) or saline. Anal canal pressure and EAS length-tension (L-T) were measured for 15 weeks after which the animals were sacrificed. Anal canal was harvested and processed for histochemical studies (Masson trichrome stain), molecular markers of fibrosis (collagen and transforming growth factor-β) and immunostaining for β catenin. Surgical myotomy of the EAS resulted in significant impairment in anal canal pressure and EAS muscle L-T function. Following myotomy, the EAS muscle was replaced with fibrous tissue. Immunostaining revealed β catenin activation and molecular studies revealed 1.5-2 fold increase in the levels of markers of fibrosis. Local injection of sFRP-2 attenuated the β catenin activation and fibrosis. EAS muscle content and function was significantly improved following sFRP-2 treatment. Our studies suggest that upregulation of Wnt signaling is an important molecular mechanism of injury related EAS muscle fibrosis and sphincter dysfunction.


Transcriptional inhibition by DNA torsional stress.
Most genome transactions are favored by DNA (-) torsional stress, i.e., unconstrained unwinding or supercoiling of DNA. A question raised here is whether DNA (+) torsional stress, which precludes DNA unwinding, could also be relevant in gene regulation. Such DNA twist dynamics could be determined by chromatin architecture.


Simultaneous quantitation of histamine and its major metabolite 1-methylhistamine in brain dialysates by using precolumn derivatization prior to HILIC-MS/MS analysis.
In nonclinical drug development targeting the central nervous system (CNS), the quantitative determination of extracellular brain concentrations of neurotransmitters is a key challenge. In some CNS disorders, the monitoring of the modified profile of neurotransmitter release such as that of histamine may explain the mechanism of action of the drug candidate. Microdialysis is a commonly used method for sampling extracellular levels of neurotransmitters/drug candidates in small laboratory animals. Detection and quantification of extracellular levels of neurotransmitters remain an analytical and technical challenge owing to the low concentrations of neurotransmitters collected, the small microdialysis sample size, and the high amount of inorganic salts. A precolumn derivatization strategy prior to hydrophilic interaction liquid chromatography (HILIC)-tandem mass spectrometry analysis is proposed to quantify histamine release after administration of a CNS research compound. Derivatization using propionic anhydride dissolved in organic solvent combined with the HILIC approach effectively eliminated three time-consuming steps, organic layer transfer, dry down, and reconstitution, all of which are required by traditional reversed-phase liquid chromatography. The formation of propionylated amides, performed under mild conditions, required no further sample cleanup. After a dual microdialysis probe implantation into the prefrontal cortex (neurotransmitters) and in the inferior vena cava of rat (drug candidate), microdialysate fractions were collected every 15 min for 8 h and stored frozen at -20 °C until analysis. The method was validated using 10 μL microdialysate, achieving low limits of quantitation of 83.4 and 84.5 pg.mL(-1) for histamine and 1-methylhistamine, respectively. These limits were suitable to assess kinetic release of neurotransmitters and are compatible with those obtained by microdialysis sampling. This method provided the required selectivity, sensitivity, accuracy, and precision to assess release kinetics of histamine and 1-methylhistamine in several hundred rat brain microdialysates after intravenous infusion of CNS drug candidates.


Can neurobiological pathogenic mechanisms of depression facilitate the development of seizure disorders?
People with epilepsy have a high risk of developing depressive disorders, and people with primary depressive disorders have a high risk of developing epilepsy. Furthermore, a lifetime history of depressive disorders has been associated with a poor response of the seizure disorder to pharmacotherapy and epilepsy surgery. The aim of this Review is to identify the principal neurobiological pathogenic mechanisms of depressive disorders with the potential to facilitate the epileptogenic process or cortical hyperexcitability in experimental animal studies or those that can aggravate known pathogenic mechanisms of epilepsy in human beings. These mechanisms include (1) a hyperactive hypothalamic-pituitary-adrenal axis; (2) structural and functional abnormalities of cortical structures; (3) increased glutamatergic and decreased GABAergic and serotonergic activity; and (4) immunological abnormalities. The data presented in this Review provide experimental evidence that might begin to explain the bidirectional relation between depressive disorders and epilepsy and that can be regarded as a source for future research.


Evaluation of EMG processing techniques using Information Theory.
Electromyographic signals can be used in biomedical engineering and/or rehabilitation field, as potential sources of control for prosthetics and orthotics. In such applications, digital processing techniques are necessary to follow efficient and effectively the changes in the physiological characteristics produced by a muscular contraction. In this paper, two methods based on information theory are proposed to evaluate the processing techniques. These methods determine the amount of information that a processing technique is able to extract from EMG signals. The processing techniques evaluated with these methods were: absolute mean value (AMV), RMS values, variance values (VAR) and difference absolute mean value (DAMV). EMG signals from the middle deltoid during abduction and adduction movement of the arm in the scapular plane was registered, for static and dynamic contractions. The optimal window length (segmentation), abduction and adduction movements and inter-electrode distance were also analyzed. Using the optimal segmentation (200 ms and 300 ms in static and dynamic contractions, respectively) the best processing techniques were: RMS, AMV and VAR in static contractions, and only the RMS in dynamic contractions. Using the RMS of EMG signal, variations in the amount of information between the abduction and adduction movements were observed. Although the evaluation methods proposed here were applied to standard processing techniques, these methods can also be considered as alternatives tools to evaluate new processing techniques in different areas of electrophysiology.


Seasonal dynamics of influenza viruses and age distribution of infected individuals across nine seasons covering 2009-2018 in Taiwan.
A swine-origin influenza A/H1N1 virus (termed A/H1N1pdm) caused a pandemic in 2009 and has continuously circulated in the human population. To investigate its possible ecological effects on circulating influenza strains, the seasonal patterns of influenza viruses and the respective age distribution of infected patients were studies. The data obtained from national influenza surveillance systems in Taiwan from July 2009 to June 2018 were analyzed. The A/H1N1pdm and A/H3N2 strains usually caused a higher ratio of severe to mild cases than influenza B. New variants of A/H1N1pdm and A/H3N2 emerged accompanied by a large epidemic peak. However, the new influenza B variants intended to circulate for several seasons before causing a large epidemic. The major group of outpatients affected by A/H1N1pdm were aged 13-23 years in the pandemic wave, and the age range of infected individuals gradually shifted to 24-49 and 0-6 years across seasons; A/H1N1pdm-infected inpatients were aged 24-49 years in 2009-2011, and the age range gradually switched to older groups aged 50-65 and >65 years. Individuals aged 0-6 or 24-49 years accounted for the majority of A/H3N2-infected outpatients across seasons, whereas most of the inpatients affected by A/H3N2 were aged >65 years. Understanding the effects of new variants and changes in dominant circulating viral strains on the age distribution of the affected human population, disease severity and epidemic levels is useful for the establishment of fine-tuned strategies for further improvement of influenza control.


Characteristics of 16-dehydroprogesterone reductase in cell extracts of the intestinal anaerobe, Eubacterium sp. strain 144.
16-Dehydroprogesterone reductase (16-DHPR) activity was present in cell extracts of Eubacterium sp. strain 144 only when the organism was grown in the presence of steroids containing a delta 16-17 double bond and C-20-ketone. Cells grown with 16-dehydropregnenolone contained 16-DHPR activity but lacked delta 4-5-3-keto steroid reductase activity. Pyruvate or sodium dithionite served as electron donors for 16-DHPR and both reactions required methyl viologen as an electron carrier. Neither NADH nor NADPH, with or without flavin nucleotides, were used by 16-DHPR. Enzyme activity was detected in the cytoplasmic fraction (40%) and membrane fraction (20%) of crude cell extracts, but 40% of the activity was unaccounted for following ultracentrifugation. 16-DHPR activity was unaffected by pH in potassium phosphate buffer over the range 5.0 to 8.5, but was inhibited by Tris-HCl above pH 7.0. 16-DHPR activity was inhibited by sulfhydryl reagents, but inhibitors of electron transport reactions or metal chelators did not affect the enzyme.


Ankylosis management with autogenous grafts: A systematic review.
A systematic review was performed to assess the clinical outcomes of the reconstructive methods using autogenous grafts for the management of temporomandibular joint (TMJ) ankylosis A comprehensive electronic and manual search of the literature without date or language restriction was performed in January 2021 to identify randomized controlled trials, prospective, and retrospective studies with the aim of comparing the various surgical modalities for TMJ ankylosis. Twenty-six publications were included: prospective (n = 17), retrospective (n = 7), randomised control trial (n = 1) and ambispective study (n = 1). Costochondral graft was the most common graft used followed by Coronoid process graft. Meta-analysis was not possible as most of studies were non-controlled in nature. Based on the available data, there was a strong evidence that autogenous grafts especially Costochondral grafts and coronoid grafts have remained one of the most favoured methods of reconstruction. Prospective and randomized control studies are recommended for the best stratification for the use of autogenous grafts for the management of TMJ ankylosis.


Sexual dimorphisms in the soma size of neurons in the brain of whiptail lizards (Cnemidophorus species).
Soma area was significantly larger in the anterior hypothalamus-preoptic area of male than female Cnemidophorus inornatus, and it was significantly larger in females than males in the ventromedial hypothalamus. These results parallel those on the volume of the brain areas in these animals, and therefore probably explain at least part of the dimorphisms seen in this sexually reproducing species. Soma size in parthenogenetic C. uniparens also parallels volume.


Bioherbicidal ability and weed management of allelopathic methyl esters from Lantana camara.
Allelochemicals are secondary metabolites which are not edible and can be used as growth regulators and bio-herbicides. The goal of current study was to assess allelopathic ability of Lantana camara (Sage-plant) flowers against weeds viz. Avena fatua (Wild oat), Euphorbia helioscopia (Sun-spurge), Chenopodium album (Goosefoot), Phalaris minor (Canary-grass), and Rumex dentatus (Knotweed). Bioassay analysis of three methanolic fractions of the Combiflash from L. camara was performed at 50%, 75% and 100% concentration using germination percentage parameters, inhibition of plumule and radicle size. The fraction II of Combiflash strongly suppressed all weeds with negligible effect on T. aestivum. Gas chromatography-mass spectroscopy was conducted for the fraction, and isolated compounds were used to perform bioassays. From fraction II GC-MS detected four methyl esters of allelopathic fatty acid viz. Methyl oleate, methyl palmitate, methyl stearate and methyl linoleate. The evaluation of physiological effects of the bioassay revealed substantial suppression of chlorophyll, antioxidant enzymes (superoxide, dismutase peroxidase) and protein material in all weeds by methyl palmitate. Bioassay activity and study of physiological parameters revealed that the effective bio-herbicidal compound in Lantana camara flowers is methyl palmitate. This is the first time that methyl palmitate (a fatty acid methyl ester) has been related to herbicidal activity in L. camara flowers. It is proposed that field studies based on hormesis research and the mechanism of action of this compound be carried out.


Contact lens fitting in high degree myopia.
Advantages and disadvantages of both spectacle and contact lens correction of high degree myopia are reviewed. Pertinent aftercare problems in this group of patients are discussed. Aspects of contact lens wear with regard to the eyelids are described. Soft contact lens problems are discussed in relation to the greater thickness of lenses of high power. Guidelines are provided for the fitting of rigid gas permeable and of soft contact lenses for this patient group. Other factors are explored in lens fitting such as over-refraction, near vision and practitioner costs. Recommendations are given for advising on lens care and aftercare.


Imaging inflamed synovial joints.
As a research tool, medical imaging has considerably increased our understanding of joint inflammation in vivo. Although conventional radiography remains important for diagnosis, other imaging modalities such as magnetic resonance imaging (MRI) and ultrasonography show considerable potential for the study of joint inflammation in the research setting. The advances in MRI and ultrasound in the last decade has lead to significant conceptual advances into the microanatomical basis for arthritis. The purpose of this chapter is to describe how MRI and ultrasound can be used in the research environment. Other imaging techniques such as computed tomography and scintigraphy have little use in studying inflamed synovial joints due to their relative inability to demonstrate inflammation, or poor resolution or both. However, molecular imaging using high-resolution positron emission tomography or single photon emission computed tomography is being increasingly used to study inflammation in the experimental setting and also in man.


Paleomicrobiology of the human digestive tract: A review.
The microbiota is a hot topic of research in medical microbiology, boosted by culturomics and metagenomics, with unanticipated knowledge outputs in physiology and pathology. Knowledge of the microbiota in ancient populations may therefore be of prime interest in understanding factors shaping the coevolution of the microbiota and populations. Studies on ancient human microbiomes can help us understand how the community of microorganisms presents in the oral cavity and the gut was shaped during the evolution of our species and what environmental, social or cultural changes may have changed it. This review cumulates and summarizes the discoveries in the field of the ancient human microbiota, focusing on the remains used as samples and techniques used to handle and analyze them.


Study protocol of a factorial trial ECHO: optimizing a group-based school intervention for children with emotional problems.
Youth mental health problems are a major public health concern. Anxiety and depression are among the most common psychological difficulties. The aim of this study is to evaluate an optimized version of a promising indicated group intervention for emotional problems. The program (EMOTION Coping Kids Managing Anxiety and Depression) targets school children 8-12 years with anxious and depressive symptoms and examines three factors. Factor 1 compares the standard EMOTION intervention delivered in 16 group-based sessions (Group), versus a partially-digital EMOTION intervention (DIGGI) delivered as eight group sessions and eight digital sessions. Both versions use virtual reality technology (VR) to improve behavioral experiments. Factor 2 compares parent participation in a 5-session parent group (high involvement) versus sharing information with parents via a brochure (low involvement). Factor 3 compares the use of a measurement and feedback system (MFS) designed to help group leaders tailor the intervention using feedback from children with no MFS. Using a cluster-randomized factorial design, 40 schools across Norway will be randomized to eight different experimental conditions based on three, two-level factors. To assess internalizing symptoms in children, children and their parents will be given self-report questionnaires pre-, post-, and one year after intervention. Parents also report on demographics, user satisfaction, personal symptoms and perception of family related factors. Teachers report on child symptoms and school functioning. Group leaders and the head of the municipal services report on implementation issues. The primary outcomes are changes in depressive and anxious symptoms. Some secondary outcomes are changes in self-esteem, quality of life, and user satisfaction. Questions regarding the consequences of the COVID-19 pandemic are included. Treatment fidelity is based on checklists from group leaders, and on user data from the participating children. This study is a collaboration between three regional centers for child and adolescent mental health in Norway. It will provide knowledge about: (1) the effect of school-based preventive interventions on anxiety and depression in children; (2) the effect of feedback informed health systems, (3) the effect and cost of digital health interventions for children, and (4) the effect of parental involvement.


SCO-spondin, a giant matricellular protein that regulates cerebrospinal fluid activity.
Cerebrospinal fluid is a clear fluid that occupies the ventricular and subarachnoid spaces within and around the brain and spinal cord. Cerebrospinal fluid is a dynamic signaling milieu that transports nutrients, waste materials and neuroactive substances that are crucial for the development, homeostasis and functionality of the central nervous system. The mechanisms that enable cerebrospinal fluid to simultaneously exert these homeostatic/dynamic functions are not fully understood. SCO-spondin is a large glycoprotein secreted since the early stages of development into the cerebrospinal fluid. Its domain architecture resembles a combination of a matricellular protein and the ligand-binding region of LDL receptor family. The matricellular proteins are a group of extracellular proteins with the capacity to interact with different molecules, such as growth factors, cytokines and cellular receptors; enabling the integration of information to modulate various physiological and pathological processes. In the same way, the LDL receptor family interacts with many ligands, including β-amyloid peptide and different growth factors. The domains similarity suggests that SCO-spondin is a matricellular protein enabled to bind, modulate, and transport different cerebrospinal fluid molecules. SCO-spondin can be found soluble or polymerized into a dynamic threadlike structure called the Reissner fiber, which extends from the diencephalon to the caudal tip of the spinal cord. Reissner fiber continuously moves caudally as new SCO-spondin molecules are added at the cephalic end and are disaggregated at the caudal end. This movement, like a conveyor belt, allows the transport of the bound molecules, thereby increasing their lifespan and action radius. The binding of SCO-spondin to some relevant molecules has already been reported; however, in this review we suggest more than 30 possible binding partners, including peptide β-amyloid and several growth factors. This new perspective characterizes SCO-spondin as a regulator of cerebrospinal fluid activity, explaining its high evolutionary conservation, its apparent multifunctionality, and the lethality or severe malformations, such as hydrocephalus and curved body axis, of knockout embryos. Understanding the regulation and identifying binding partners of SCO-spondin are crucial for better comprehension of cerebrospinal fluid physiology.


Lack of Association between Serum Chitotriosidase Activity and Arterial Stiffness in Type 2 Diabetes without Cardiovascular Complications.
Chitotriosidase (CHIT), a mammalian chitinase secreted by neutrophils and activated macrophages, is increased in both cardiovascular disease (CVD) and type 2 diabetes (T2D). Arterial stiffness rises early in T2D and increases the risk of CVD. The aim of this study is to evaluate CHIT activity as an early biomarker of arterial stiffness in people with T2D free from overt vascular complications. In this cross-sectional study, arterial stiffness as measured using standard pulse wave velocity (PWV) was evaluated in 174 people with T2D without overt vascular disease. Then, we measured CHIT serum activity with an electrochemiluminescence assay in two subgroups of participants: 35 with the highest (high-PWV) and 40 with the lowest (low-PWV) PWV values. CHIT activity was no different between the low-PVW and high-PWV groups (12.7 [9.6-17.9] vs. 11.4 [8.8-15.0] nmol/mL/h, respectively). Compared with the low-PWV group, the high-PWV participants were older (p < 0.001); had a longer duration of diabetes (p = 0.03); higher ankle-brachial index ABI (p = 0.04), systolic blood pressure (p = 0.002), diastolic blood pressure (p = 0.005), fasting blood glucose (p = 0.008), and HbA1c (p = 0.005); and lower eGFR (p = 0.03) and body mass index (BMI) (p = 0.01). No association was present with sex, duration of diabetes, age, BMI, peripheral blood pressure, laboratory parameters, and glucose-lowering medications or ongoing antihypertensive therapy. Although no association was found, this study provides novel data about the association of CHIT activity with CVD, focusing on a specific outcome (arterial stiffness) in a well-defined population of subjects with T2D without established CVD.


Analgesic Pump Tubing Securement to Prevent Dislodgement of Peripheral Vein Indwelling Catheter.
This study aims to compare the incidence of complications when using a new approach to secure an indwelling peripheral venous catheter (PVC), involving tying of the tube with a surgical knot at two places and several layers of elastic adhesive bandage, with a standard approach using sterile, transparent, and protective film. This study enrolled 311 consecutive adults undergoing thoracoscopic lobectomy under general anesthesia at Taizhou Hospital of Zhejiang Province between October 2017 and May 2018. Patients were randomized to experimental and control groups and were followed for up to 72 hours. The primary endpoint was dislodgement of the PVC. Secondary endpoints were blood in the catheter; analgesia pump obstruction alarm; time taken and cost of PVC replacement; replacement of securing materials and analgesia pump line; and time and cost of replacing them. All adverse events were recorded. Final analysis included 248 patients (experimental group: n = 126; control group: n = 122). PVC dislodgement was less frequent in the experimental group than in the control group. In the control group, 78.7% of patients required replacement of securing materials (costing 37 cents each time) and 13.1% required PVC replacement (costing 3.6 dollars each time), necessitating additional nursing time. No patients in the experimental group required replacement of the PVC or securing materials. Blisters were less common in the experimental group than in the control group (0% vs 9.84%, P < .001). No patients had limb edema. This new method of securing an analgesia pump line can reduce traction on the indwelling PVC, lowering the dislodgement rate.


[Persistent atelectasis secondary to an endobronchial tubercular granuloma in primary tuberculosis: presentation of a case with a favorable outcome].
The Authors report a case of tuberculous endobronchial granuloma observed in a two years old child affected by primary tuberculosis. The more important aspects of the case are its rarity, the pathogenesis, its differential diagnosis, and the determining importance of the surgical operation for diagnosis and therapy.


Lipopolysaccharide stimulates syntheses of toll-like receptor 2 and surfactant protein-A in human alveolar epithelial A549 cells through upregulating phosphorylation of MEK1 and ERK1/2 and sequential activation of NF-κB.
Surfactant proteins (SPs) and toll-like receptors (TLRs) contribute to regulation of sepsis-induced acute lung injury. Lipopolysaccharide (LPS) is one of the major causes of septic shock. This study was designed to evaluate the effects of LPS on the regulation of tlr-2 and sp-a gene expression in human alveolar epithelial A549 cells and the possible mechanisms. Exposure of A549 cells to LPS increased the expressions of TLR2 and SP-A mRNA and protein in time-dependent manners. A search using a bioinformatic approach found that there are several nuclear factor kappa-B (NF-κB)-DNA-binding motifs in the promoter region of the tlr2 and sp-a genes. Immunoblotting analyses revealed that exposure to LPS time-dependently enhanced the translocation of NF-κB from the cytoplasm to nuclei. Analyses of an electrophoretic mobility shift assay further showed that LPS augmented the transactivation activity of NF-κB to its consensus oligonucleotides in A549cells. Sequentially, treatment of A549 cells with LPS increased phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38-mitogen-activated protein kinase (p38MAPK), and MAPK kinase-1 (MEK1). Pretreatment with PD98059, an inhibitor of ERK1/2, significantly decreased LPS-induced TLR2 and SP-A mRNA expression.


Evaluation of a panel of circulating DNA, RNA and protein potential markers for pathologies of pregnancy.
Among markers of pregnancy complications, corticotropin-releasing hormone (CRH) mRNA, long pentraxin 3 (PTX3) protein and fetal and total DNA had been reported to be increased in the plasma of women with overt preeclampsia (PE). We developed an optimized protocol to evaluate whether concentrations of CRH mRNA, PTX3 mRNA and protein, fetal and/or total DNA are increased in fetal growth restriction (FGR), and whether they predict complications of pregnancy. The protocol included a preamplification step to enrich rare mRNA species. CRH and PTX3 mRNA, DNA and PTX3 protein were measured in the plasma of women with PE or FGR, in women at risk of developing these pathologies and in healthy women matched for gestational age. CRH mRNA, fetal and/or total DNA and PTX3 protein were significantly increased in women with overt PE when compared to controls. Pregnant women who later developed PE or FGR during pregnancy showed total DNA levels that were significantly increased before the onset of both pathologies, while RNA markers were increased only in women who later developed PE. Our protocol for plasma RNA quantification may allow for the extension of a panel of predictive markers to be investigated in larger patient cohorts.


Sexual dysfunction in women with type 1 diabetes in Norway: A cross-sectional study on the prevalence and associations with physical and psychosocial complications.
To estimate the prevalence of sexual dysfunction in women with type 1 diabetes (T1D) compared with women without diabetes and to analyse associations between sexual dysfunction and the presence of chronic physical diabetes complications, diabetes distress and depression in women with T1D. This cross-sectional study was conducted in Norway, and 171 women with T1D and 60 controls completed the Female Sexual Function Index (FSFI) and the Hospital Anxiety and Depression Scale (HADS). Diabetes distress was assessed with the Problem Areas in Diabetes (PAID) scale. Data on diabetes complications were retrieved from medical records. We performed logistic regression to estimate differences in the prevalence of sexual dysfunction (defined as FSFI ≤26.55) between women with T1D and women without diabetes and to examine associations of sexual dysfunction with chronic diabetes complications, diabetes distress and depression in women with T1D. The prevalence of sexual dysfunction was higher in women with T1D (50.3%) compared with the controls (35.0%; unadjusted odds ratio [OR] 1.89 [95% confidence interval (CI) 1.06-3.37]; adjusted OR 1.93 [1.05-3.56]). In women with T1D, sexual dysfunction was associated with both diabetes distress (adjusted OR 1.03 [1.01-1.05]) and depression (adjusted OR 1.28 [1.12-1.46]), but there were no clear associations with chronic diabetes complications (adjusted OR 1.46 [0.67-3.19]). This study suggests that sexual dysfunction is more prevalent in women with T1D compared with women without diabetes. The study findings emphasize the importance of including sexual health in relation to diabetes distress and psychological aspects in diabetes care and future research.


Immunologic studies in a case of baker's asthma.
A 28-year-old baker with 13 years of occupational experience has developed, over the past several years, sinusitis, rhinitis, contact dermatitis, and asthma. Clinically, all of his symptoms were felt to be related to occupational exposure. Immunologic evaluation consisted of the following tests: intradermal skin testing, leukocyte histamine release, total serum IgE, PK transfer with immunoadsorption, and specific antigen bronchial challenge. Analysis of results would tend to implicate a type I, IgE-mediated immunologic reaction.


Study of the distribution of Glycyrrhiza uralensis production areas as well as the factors affecting yield and quality.
Wild licorice in China is mainly distributed in northern China, such as Gansu, Ningxia, and Inner Mongolia Provinces. The origin of wild licorice has varied among historical periods. The cultivated origin of planted licorice has the same as 59.26% of wild licorice. The distribution of cultivated licorice was shifted to the northwest relative to that of wild licorice. The yield and quality of cultivated licorice vary greatly from different origins, showing a certain pattern of variation from west to east. The same batch of licorice seedlings was planted at 8 sites overlapping the main licorice production areas in China. The yield and quality of licorice in the Baicheng experimental plot were low. The yield of licorice in the Jingtai and Altay experimental plots was high, but the quality was poor. The quality of licorice in Chifeng and Yuzhong experimental sites was high, but the yield was low. Principal component analysis of environmental and soil factors generated five characteristic roots with a cumulative contribution rate of 80%, three of which were related to soil and referred to as the soil charge factor, soil water factor, and soil nutrient factor, and the load coefficients of the water and nutrient factor were the largest. Soil conditions, especially water and nutrients, might have a substantial effect on the observed changes in the licorice production area. Generally, the regulation of water and nutrients merits special attention when selecting areas for the production and cultivation of licorice. This study can provide reference for the selection of cultivated licorice production areas and the research of high-quality cultivation techniques.