Graphene quantum dot cross-linked carboxymethyl cellulose nanocomposite hydrogel for pH-sensitive oral anticancer drug delivery with potential bioimaging properties.
Herein, graphene quantum dots (GQDs) were introduced as a novel and safe crosslinker for carboxymethyl cellulose to make biodegradable and biocompatible hydrogels. The casting was used as a simple method for the preparation of the CMC/GQDs films. Effects of the GQDs percentage on the physicochemical properties of the films were studied, and several characterizations were performed including Fourier transform infrared spectroscopy, UV-vis spectroscopy, scanning electron microscopy, gas permeability, and mechanical testing analysis. The CMC/GQDs showed a pH-sensitive swelling and degradation with improved tensile strength. Fluorescent properties were also studied to evaluate the potential of the prepared CMC/GQDs nanocomposite for fluorescent bioimaging applications. Drug delivery property of the CMC-GQDs were studied using doxorubicin (DOX) as a model anticancer drug. Cytotoxicity studies were carried out using human colon adenocarcinoma HT29 cells. The prepared CMC/GQDs exhibited biocompatibility and pH-sensitive drug delivery behavior which proposed the prepared nanocomposite hydrogel has the potential to be used as a pH-triggered site-specific drug delivery system.


Continuous Positive Airway Pressure treatment of premature infants; application of a computerized decision support system.
The predictions of a computerized decision-support system (CDSS) are compared to clinical data obtained from a group of premature infants. The infants were suffering from respiratory distress syndrome (RDS) and were treated by the Continuous Positive Airway Pressure (CPAP) therapy. The predictions of the CDSS are found to be in general agreement with clinical measurements. The CDSS is also used to determine the effect of low level oxygen treatment on arterial oxygen pressure if the infant׳s oxygenation is low despite CPAP therapy. Based on the computational results, application of low levels of supplemental inspired fraction of oxygen ( [Formula: see text] ) would result in significant improvement in oxygenation of premature infants provided such treatment is carefully controlled to avoid hyperoxemia.


Antibody Sequence and Structure Analyses Using IMGT®: 30 Years of Immunoinformatics.
IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org , the global reference in immunogenetics and immunoinformatics, was created in 1989 by Marie-Paule Lefranc (Université de Montpellier and CNRS) to manage the huge diversity of the antigen receptors, immunoglobulins (IG) or antibodies, and T cell receptors (TR) of the adaptive immune responses. The founding of IMGT® marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. IMGT® standardized analysis of the IG, TR, and major histocompatibility (MH) genes and proteins bridges the gap between sequences and three-dimensional (3D) structures, for all jawed vertebrates from fish to humans. This is achieved through the IMGT Scientific chart rules, based on the IMGT-ONTOLOGY axioms, and primarily CLASSIFICATION (IMGT gene and allele nomenclature) and NUMEROTATION (IMGT unique numbering and IMGT Colliers de Perles). IMGT® comprises seven databases (IMGT/LIGM-DB for nucleotide sequences, IMGT/GENE-DB for genes and alleles, etc.), 17 tools (IMGT/V-QUEST, IMGT/JunctionAnalysis, IMGT/HighV-QUEST for NGS, etc.), and more than 20,000 Web resources. In this chapter, the focus is on the tools for amino acid sequences per domain (IMGT/DomainGapAlign and IMGT/Collier-de-Perles), and on the databases for receptors (IMGT/2Dstructure-DB and IMGT/3D-structure-DB) described per receptor, chain, and domain and, for 3D, with contact analysis, paratope, and epitope. The IMGT/mAb-DB is the query interface for monoclonal antibodies (mAb), fusion proteins for immune applications (FPIA), composite proteins for clinical applications (CPCA), and related proteins of interest (RPI) with links to IMGT® 2D and 3D databases and to the World Health Organization (WHO) International Nonproprietary Names (INN) program lists. The chapter includes the human IG allotypes and antibody engineered variants for effector properties used in the description of therapeutical mAb.


Direct and Indirect Determinants of the Patient Global Assessment in Rheumatoid Arthritis: Differences by Level of Disease Activity.
In rheumatoid arthritis (RA), the patient global assessment (PGA) has been strongly associated with pain severity, but less often with other measures, including disease activity measures. We tested whether RA activity and psychological measures had direct associations with the PGA or indirect associations that were mediated by pain. We also tested whether the correlates of the PGA differed with the degree of RA activity. We studied 260 patients with active RA on 2 visits in a prospective longitudinal study. We used path analysis to test direct and indirect associations of Disease Activity Score in 28 joints (DAS28), morning stiffness, Health Assessment Questionnaire (HAQ), fatigue, physical role limitations, social functioning, depressive symptoms, and health distress with the PGA. Among the 509 visits, the median PGA score was 50 (25th-75th percentile: 24-66). Pain severity had the strongest association with the PGA, but direct associations were also found for morning stiffness severity, health distress, fatigue, and DAS28. Morning stiffness severity, DAS28, health distress, and HAQ were also indirectly associated with the PGA through pain. Among visits with DAS28 ≥5.4, pain, morning stiffness severity, and HAQ were the only determinants of the PGA. Among visits with DAS28 <4.2, health distress and age were additional determinants, and fatigue was marginally associated with the PGA. Although pain was the strongest determinant of the PGA in RA, morning stiffness severity, health distress, fatigue, and DAS28 were also important. Determinants of the PGA differed with RA activity, with health distress, age, and to a lesser degree, fatigue, contributing only in patients with less active RA.


Abnormal recruitment of working memory updating networks during maintenance of trauma-neutral information in post-traumatic stress disorder.
Post-traumatic stress disorder (PTSD) is characterised by disturbances in concentration and memory, symptoms which are a source of further distress for patients. Related to this, abnormalities in underlying working memory (WM) systems have been identified [Clark, C.R., McFarlane, A.C., Morris, P., Weber, D.L., Sonkkilla, C., Shaw, M.E., Marcina, J., Tochon-Danguy, H.J., Egan, G.F., 2003. Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study. Biological Psychiatry 53, 474-481.], indicating dysfunction in left hemisphere brain regions. In this study, we performed functional magnetic resonance imaging (fMRI) in 13 patients with severe PTSD and matched non-traumatized Controls, during performance of visuo-verbal tasks that involved either maintenance or continual updating of word stimuli in WM. The PTSD group failed to show differential activation during WM updating, and instead appeared to show abnormal recruitment of WM updating network regions during WM maintenance. These regions included the bilateral dorsolateral prefrontal cortex (DLPFC) and the inferior parietal lobe (IPL). Several other regions were significantly more activated in Controls than in PTSD during WM updating, including the hippocampus, the anterior cingulate (AC), and the brainstem pons, key regions that are consistently implicated in the neurobiology of PTSD. These findings suggest compensatory recruitment of networks in PTSD normally only deployed during updating of WM and may reflect PTSD patients' difficulty engaging with their day-to-day environment.


Amide derivatives of [5-chloro-6-(2-chloro/fluorobenzoyl)-2-benzoxazolinone-3-yl]acetic acids as potential analgesic and anti-inflammatory compounds.
In this study, we have explored the prevention of gastric side effects such as gastric lesions and bleeding while maintaining the high analgesic and anti-inflammatory activities by the derivatization of the carboxylate moiety into amides in [5-chloro-6-(2-chloro/fluorobenzoyl)-2-benzoxazolinone-3-yl]acetic acids. We have tested the analgesic and anti-inflammatory activities of the synthesized compounds in vivo by using p-benzoquinone-induced writhing test and carrageenan-induced hind paw edema model, respectively. Compounds 3a, 3d, 3e, 3j and 3k potent analgesic and anti-inflammatory activities without gastric lesions in the tested animals. Therefore, conversion of the carboxylate moiety into certain amide derivatives generated potent analgesic and anti-inflammatory compounds while eliminating the gastrointestinal side effects. Cyclooxygenase (COX)-selectivity of the active compounds was also investigated by using in vitro human whole blood assay. Compounds 3a, 3e, 3h and 3k selective inhibition of COX-2 to some extent although the inhibitory activity was not very potent.


Measuring the cost of reproduction : IV. Predation experiments with Daphnia pulex.
Gravid and barren Daphnia pulex were exposed to a variety of predators in laboratory aquaria. Small fish (guppies, sticklebacks and shiner fry) consistently preferred the gravid females, establishing the existence of a behavioural cost of reproduction. However, no such cost was associated with predation by more efficient visual predators (sunfish) or by nonvisual predators (hydras), and the excess of gravid females eaten by backswimmers was found to be attributable to their distribution in the water column. Moreover, the cost associated with predation by small fish was observed only when the Daphnia were presented against a light background, and was abolished when a dark background was substituted. In a further series of experiments with guppies we attempted to show that each egg added to the brood caused a decrease in survival; in two such experiments survival rate was related to body size but not to fecundity, while in a third the effect of body size did not appear, and a negative correlation between survival and fecundity could be demonstrated. Although these experiments unambiguously demonstrate a cost of reproduction they also illustrate the elusiveness of the phenomenom and emphasize the need to develop theories which specify the type and magnitude of costs generated by different ways of life.


Hemodynamic effects of substance P and its receptor antagonist RP67580 in anesthetized rats with carbon tetrachloride-induced cirrhosis.
Substance P (SP) is a vasodilator that may contribute to systemic and splanchnic vasodilatation in cirrhosis. The aim of this study was to determine the effects of SP (dose--13 pg/kg) and its specific inhibitor, RP67580 (dose--300 microg/kg) on mean arterial pressure (MAP) and portal pressure (PP) in cirrhotic rats and controls. MAP and PP were measured before and after administering SP and RP67580. Additionally, a small group of cirrhotic rats were pretreated with L-NAME to block the effects of nitric oxide (NO) before measurements. SP produced transient systemic hypotension in both groups. SP caused a significant increase in PP in cirrhotic rats and a decrease in PP in controls. RP67580 reduced the hypotensive effect of SP, but not completely. RP67580 decreased PP in the cirrhotic group but not in controls. In cirrhotic rats pretreated with L-NAME, SP administration caused a significant decrease in MAP but no significant change in PP. Exogenous SP increases PP and decreases MAP in cirrhotic rats. RP687580 decreases PP and reduces SP-induced hypotension in cirrhotic rats. NO blockade abolishes the effect of SP on PP. SP contributes to splanchnic vasodilatation in cirrhosis and this effect may be mediated by NO.


Responses of C4 grasses to atmospheric CO2 enrichment : I. Effect of irradiance.
The growth and photosynethetic responses to atmospheric CO2 enrichment of 4 species of C4 grasses grown at two levels of irradiance were studied. We sought to determine whether CO2 enrichment would yield proportionally greater growth enhancement in the C4 grasses when they were grown at low irradiance than when grown at high irradiance. The species studied were Echinochloa crusgalli, Digitaria sanguinalis, Eleusine indica, and Setaria faberi. Plants were grown in controlled environment chambers at 350, 675 and 1,000 μl 1-1 CO2 and 1,000 or 150 μmol m-2 s-1 photosynthetic photon flux density (PPFD). An increase in CO2 concentration and PPFD significantly affected net photosynthesis and total biomass production of all plants. Plants grown at low PPFD had significantly lower rates of photosynthesis, produced less biomass, and had reduced responses to increases in CO2. Plants grown in CO2-enriched atmosphere had lower photosynthetic capacity relative to the low CO2 grown plants when exposed to lower CO2 concentration at the time of measurement, but had greater rate of photosynthesis when exposed to increasing PPFD. The light level under which the plants were growing did not influence the CO2 compensation point for photosynthesis.


QTL for spike-layer uniformity and their influence on yield-related traits in wheat.
Common wheat (Triticum aestivum L.) is one of the most important food crops worldwide. Wheat spike-layer uniformity related traits (SLURTs) were complex traits that directly affect yield potential and appearance. In this study, quantitative trait locus (QTL) for five SLURTs among inter-tillers were first documented using a recombinant inbred line (RIL) mapping population derived from a cross between Kenong9204 and Jing411 (represented by KJ-RILs). Genetic relationships between SLURTs and yield were characterized in detail. The trait phenotypic performances for the 188 KJ-RILs and their parents were evaluated in eight different environments. The genetic data included in a high-density genetic map derived from the Affymetrix 660 K SNP Array and the corresponding genotypes in each lines. Of 99 putative additive QTL 11 were stable across environments and 57 showed significant additive-by-environment interaction effects. These QTL individually explained 1.05-39.62% of the phenotypic variance, with log of odds (LOD) values ranging from 2.00 to 34.01. Genetic relationships between SLURTs and yield indicated that plants with slight uneven spike spatial distribution should be an ideotype for super high-yield in wheat. The present study will provide assistance in understanding the genetic relationships between SLURTs and yield potential. The 11 stable QTL for SLURTs identified herein may facilitate breeding new wheat varieties with scientifically reasonable spike-layer distribution by marker assisted selection.


Flowing down the river: Influence of hydrology on scale and accuracy of elemental composition classification in a large fluvial ecosystem.
Trace metals found in the calcified structures of fish (i.e. otolith, scales and vertebrae) serve as proxies for the ambient water composition at the time of mineralization, and these trace metals are increasingly used as a tool for assessing population structure and the migratory patterns of fish. However, the appropriate scale (e.g. resolution) for such applications can be uncertain because of a poor understanding of the spatiotemporal variations of metal-to-calcium ratios (Me:Ca) in the studied watersheds. This study aims to assess Me:Ca spatiotemporal variability within the St. Lawrence River and nine major tributaries and evaluate the ability of random-forest models to correctly identify rivers on the basis of their elemental composition. We tested the influence of daily discharge on four measured ratios (Sr:Ca, Ba:Ca, Mg:Ca and Mn:Ca) to document local and regional trace element sources and dynamics. The four element ratios displayed a low spatiotemporal variation, reflecting a marked stability over time. We observed that most element- and tributary-specific concentration-discharge relationships were either not significant or showed a weak influence, thereby confirming a stable point source dynamic. The classification performance based on a four-element model (Sr:Ca, Ba:Ca, Mg:Ca and Mn:Ca) produced a classification accuracy of 92.5%, which correspond to a small decrease of accuracy compared to the full model (25 elements, 96.6% of correct classification). A classification based on two elements (Sr:Ca and Ba:Ca) produced a lower classification accuracy (72.6%). Classification errors related mainly to tributaries in close proximity, a problem tempered by grouping these geochemically similar watersheds. Our results show that surveys of the elemental fingerprint of regional tributaries within a given region can provide critical information to determine the appropriate scale (tributary or watershed) for trace metal analysis of the hard-calcified parts of fish.


Dynamic changes in the distribution of facial and abdominal adipose tissue correlated with surgical treatment in acromegaly.
Acromegaly is a systemic metabolic disease. Growth hormone (GH) have a significant impact on adipose tissue (AT). A huge reduction of serum GH after surgical treatment may cause substantial AT redistribution. The objective of this study was to illustrate the dynamic changes in distribution of facial and abdominal AT correlated with surgical treatment in patients with acromegaly. Abdominal AT in 17 acromegaly patients (group 1) was studied longitudinally preoperatively and 1 month to 1 year postoperatively. The facial and abdominal subcutaneous AT (fSAT and aSAT) of another 17 acromegaly patients (group 2) were compared with 7 nonfunctional pituitary adenoma (NFPA) controls. The areas of fSAT, aSAT, and visceral adipose tissue (VAT) were obtained by MRI and quantified by image analysis software, and intrahepatic lipid (IHL) was assessed by 1H magnetic resonance spectroscopy (MRS). Abdominal adipose tissue (aSAT, VAT, and IHL) increased overall after surgical treatment. However, IHL first decreased and then continuously increased during the follow-up. Compared with the increased amount of aSAT, the fSAT amount decreased after surgical treatment. The inconsistency of this phenomenon did not appear in the NFPA control subjects. The perioperative dynamic distribution of the facial and abdominal fat in acromegaly revealed regional differences in the intricate effect of GH on adipose tissue. Reduction of serum GH after surgical treatment of acromegaly was associated with dynamic increases of IHL, abdominal visceral, and subcutaneous fat, but a reduction of facial subcutaneous fat.


Perioperative ultrasound-guided wire marking of calcific deposits in calcifying tendinitis of the rotator cuff.
The identification of a calcific deposit in the rotator cuff can often cause difficulties. A new technique is described to identify the calcific deposit perioperatively with a ultrasound-guided wire. The technique allows a safe direct marking of calcific deposits making the procedure faster especially in difficult cases.


Dynamic Ca2+ sensitivity stimulates the evolved SARS-CoV-2 spike strain-mediated membrane fusion for enhanced entry.
Mutations in the spike protein generated a highly infectious and transmissible D614G variant, which is present in newly evolved fast-spreading variants. The D614G, Alpha, Beta, and Delta spike variants of SARS-CoV-2 appear to expedite membrane fusion process for entry, but the mechanism of spike-mediated fusion is unknown. Here, we reconstituted an in vitro pseudovirus-liposome fusion reaction and report that SARS-CoV-2 wild-type spike is a dynamic Ca2+ sensor, and D614G mutation enhances dynamic calcium sensitivity of spike protein for facilitating membrane fusion. This dynamic calcium sensitivity for fusion is found to be higher in Alpha and Beta variants and highest in Delta spike variant. We find that efficient fusion is dependent on Ca2+ concentration at low pH, and the fusion activity of spike dropped as the Ca2+ level rose beyond physiological levels. Thus, evolved spike variants may control the high fusion probability for entry by increasing Ca2+ sensing ability.


Hypoglycemia possibly caused by CYP2C9-mediated drug interaction in combination with bucolome: a case report.
Bucolome is a non-steroidal anti-inflammatory drug and uricosuric agent, currently used only in Japan. It is known to induce drug interactions by inhibiting cytochrome P450 (CYP) 2C9. It is often used to enhance the anticoagulant effect of warfarin by utilizing its drug interactions. There are only a few reports on drug interactions of bucolome and the mechanism remain poorly understood. An 81-year-old woman with a history of type 2 diabetes mellitus was taking glimepiride 2 mg/day and voglibose 0.6 mg/day. After hospitalization, the patient underwent surgical aortic valve replacement surgery (day 0). Glimepiride and voglibose were resumed on the second postoperative day (day 2), and warfarin was started to prevent thromboembolism. Since the prothrombin time-international normalized ratio on day 9 was low at 1.24, 300 mg/day of bucolome was added to enhance the effect of warfarin. A gradual decrease in blood glucose levels was observed from the day after bucolome administration was initiated. Hypoglycemia in the 56-57 mg/dL range occurred before lunch and dinner on the 6th day (day 14) of bucolome administration, due to which voglibose was discontinued. Hypoglycemia below 70 mg/dL was not observed thereafter, and the general condition of the patient was stable. Based on the clinical course and literature review, we believe that hypoglycemia in the present case was due to a drug interaction, caused by inhibition of CYP2C9 by bucolome and competitive inhibition of CYP2C9 by warfarin, which affected the pharmacokinetics of glimepiride. The possibility of hypoglycemia due to drug interactions should be considered by physicians, when bucolome is included to enhance the effect of warfarin, in patients taking glimepiride.


Cadmium effects and biochemical status in hamsters following acute exposure in late gestation.
A normally teratogenic dose of cadmium ions administered to hamsters late in gestation does not cross the placental barrier nor does it result in placental pathology. Our finding, which differs from data for other rodents, may be due to differences in the chemical status of cadmium in the placental cytosols.


Association of State-Level Firearm-Related Deaths With Firearm Laws in Neighboring States.
Firearms are easily transported over state borders; hence permissive firearm laws in one state may have an interstate association with firearm-related deaths in nearby states. To examine whether certain firearm laws have an interstate association with firearm-related deaths in nearby states. This cross-sectional observational study used data on state firearm-related deaths in the 48 contiguous states of the US between January 1, 2000, and December 31, 2019. A spatial autoregressive model with fixed effects for state and year was used to evaluate within-state, interstate, and overall associations between firearm laws and firearm-related deaths. Analyses were performed during January 2022. The following 9 types of laws were evaluated: universal background checks for all firearms purchase, background checks for handgun sales at gun shows, license requirement to purchase all firearms, state dealer license requirement for handgun sales, requirement of retaining records of handgun sales, ban on purchasing a handgun on behalf of another, prohibition of firearm possession by persons who committed violent misdemeanors, required relinquishment of firearms for persons becoming prohibited from possessing them, and discretion in granting a concealed carry permit. State-level total firearm-related death rates, suicide rates, and homicide rates. In sum, the study period included 662 883 firearm-related deaths of all intents. License requirement for firearm purchase had a within-state association (effect size, -1.79 [95% CI, -2.73 to -0.84]), interstate association (effect size, -10.60 [95% CI, -17.63 to -3.56]), and overall association (effect size, -12.38 [95% CI, -19.93 to -4.83]) per 100 000 population decrease in total firearm-related deaths. This law also had within-state association (effect size, -1.26 [95% CI, -1.72 to -0.80]), interstate association (effect size, -9.01 [95% CI, -15.00 to -3.02]), and overall association (effect size, -10.27 [95% CI, -16.53 to -4.01]) per 100 000 population decrease in firearm-related homicide. The findings of this pooled cross-sectional analysis suggest that certain firearm laws in one state were associated with other states' firearm-related deaths. Synergic legislative action in adjacent states, federal firearm legislation, and measures that reduce migration of firearms across state borders should be part of the overarching strategy to prevent firearm-related deaths.


Estrogen-sensitive projections from the medial preoptic area to the dorsal pontine tegmentum, including Barrington's nucleus, in the rat.
Urinary incontinence affects a significant number of post-menopausal women. There is conflicting evidence whether voiding symptoms in these women are related to hypoestrogenism or aging itself. This neuroanatomical study was designed to determine whether a specific central nervous system (CNS) pathway that projects to the pontine micturition center (PMC, also known as "Barrington's nucleus") is estrogen sensitive in a rat model. A fluorescent retrograde tracer was injected into the dorsal pontine tegmentum of adult female Sprague-Dawley rats to identify neurons in the medial preoptic area (MPA) that project to the PMC. Immunohistochemistry was performed using antibodies directed against estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) to identify estrogen-sensitive neurons. The brain sections were examined using fluorescence microscopy to identify cells that project to the PMC (contain fluorescent tracer) and also express ER (are immunoreactive for ER). There are neurons in the MPA that are double labeled (contain fluorescent tracer and express ERalpha, but not ERbeta), showing that a subset of neurons projecting from the MPA to the PMC is estrogen sensitive. A subset of estrogen-sensitive neurons projects from the MPA to the PMC in rats, raising the possibility that indirect estrogenic regulation of forebrain neuronal function may modulate the micturition reflex. Future development of drugs that alter the function of this estrogen-sensitive CNS pathway may provide therapeutic strategies to treat post-menopausal incontinence.


Phenolic excipients of insulin formulations induce cell death, pro-inflammatory signaling and MCP-1 release.
Skin reactions at the infusion site are a common side effect of continuous subcutaneous insulin infusion therapy. We hypothesized that local skin complications are caused by components of commercial insulin formulations that contain phenol or m-cresol as excipients. The toxic potential of insulin solutions and the mechanisms leading to skin reactions were explored in cultured cells. The toxicity of insulin formulations (Apidra, Humalog, NovoRapid, Insuman), excipient-free insulin, phenol and m-cresol was investigated in L929 cells, human adipocytes and monocytic THP-1 cells. The cells were incubated with the test compounds dose- and time-dependently. Cell viability, kinase signaling pathways, monocyte activation and the release of pro-inflammatory cytokines were analyzed. Insulin formulations were cytotoxic in all cell-types and the pure excipients phenol and m-cresol were toxic to the same extent. P38 and JNK signaling pathways were activated by phenolic compounds, whereas AKT phosphorylation was attenuated. THP-1 cells incubated with sub-toxic levels of the test compounds showed increased expression of the activation markers CD54, CD11b and CD14 and secreted the chemokine MCP-1 indicating a pro-inflammatory response. Insulin solutions displayed cytotoxic and pro-inflammatory potential caused by phenol or m-cresol. We speculate that during insulin pump therapy phenol and m-cresol might induce cell death and inflammatory reactions at the infusion site in vivo. Inflammation is perpetuated by release of MCP-1 by activated monocytic cells leading to enhanced recruitment of inflammatory cells. To minimize acute skin complications caused by phenol/m-cresol accumulation, a frequent change of infusion sets and rotation of the infusion site is recommended.


Disrupting effects of the emerging contaminant octylmethoxycinnamate (OMC) on human umbilical artery relaxation.
Cardiovascular diseases (CVD) represent the number one cause of death worldwide. The vascular endothelium may play a role in the pathophysiology of CVD diseases. Octylmethoxycinnamate (OMC) is a UV-B filter (CAS number: 5466-77-3) widely used worldwide in numerous personal care products, including sunscreens, daily creams, and makeup. This UV-B filter is considered an endocrine disruptor. Therefore, this investigation aimed to evaluate the direct effects of OMC in human umbilical arteries (HUAs) with endothelium and the possible mechanisms involved in the response. The results demonstrated that OMC exerts a rapid (non-genomic) and endothelium-dependent arterial relaxant effect on HUAs previously contracted with serotonin (5-HT) and Histamine (His). On the other hand, when HUAs were contracted with potassium chloride (KCl), the relaxing effect was only observed in HUAs without endothelium, and it appeared to be inhibited in HUAs with endothelium. Thus, the vasorelaxant effect of OMC depends on the endothelium and depends on the contractile agent used, suggesting that OMC may act through different signaling pathways. Furthermore, computational modulation studies, corroborated the binding of OMC to all the proteins under investigation (eNOS, COX-2, ET-1, and TxA2), with higher affinity for COX-2. In summary, the vascular effect of OMC may involve activating different pathways, i.e., acting through the NO pathway, COX pathway, or activating the endothelin-1 pathway.


Repeated partial hepatectomy as a promoting stimulus for carcinogenic response of liver to nitrosamines in rats.
Partial hepatectomy 24 h before a single i.p. dose of dimethylnitrosamine, diethylnitrosamine or ethylmethylnitrosamine increased the carcinogenic response in the liver of rats as determined by the number of tumours and the number of "focal proliferations" produced. Secondly, in rats given a single i.p. dose of diethylnitrosamine, 3 partial hepatectomies 5, 10 and 15 weeks after dosing the animals increased the carcinogenic response in the liver. The stimulus of repeated partial hepatectomy therefore appears to act as a "promoting agent" for liver carcinogenesis, that is if the single dose of diethylnitrosamine is regarded as an "initiating agent" in the terms of the two-stage hypothesis.


Type II endoleak prevention with coil embolization during endovascular aneurysm repair in high-risk patients.
This study evaluated endoleak level and size decrease of infrarenal abdominal aortic aneurysm (AAA) after endovascular aneurysm repair (EVAR) with coil embolization in patients at high risk for type II endoleak. Between 2009 and 2013, 83 of 187 patients (44.3%) who underwent EVAR for AAA also underwent coil embolization of the aneurysm sac immediately after complete stent graft release because of risk factors for type II endoleak, including absence of a circumferential thrombus, two or more pairs of patent lumbar arteries, or a patent inferior mesenteric artery. Coil embolization was achieved using a 4F catheter with a microcatheter placed between the stent graft and the aneurysm wall. Computed tomography and color duplex ultrasound imaging were performed 1, 6, 12, and 24 months later to look for an endoleak and assess aneurysm sac diameter. Mean follow-up was 24 ± 11 months (range, 6-53 months). A mean of 12 coils (range, 4-23) was used. Technical success was achieved in all patients, with no procedurally related complications. Follow-up computed tomography showed type II endoleak in one patient. Aneurysm sac diameter was significantly decreased after 6 months (P = .001), 12 months (P = .001), and 24 months (P = .001). Surgery was required in one patient for common femoral artery occlusion unrelated to the procedure and in another patient for distal type I endoleak. Aneurysm sac coil embolization during EVAR for patients at risk for type II endoleak is technically feasible, safe, and effective in preventing type II endoleak. This procedure leads to rapid AAA shrinkage. Thus, coil embolization could be used routinely to improve EVAR outcomes for patients at risk for type II endoleak.


Direct video-microscopic observation of the dynamic effects of medical ultrasound on ultrasound contrast microspheres.
Ultrasound can cause destruction of microbubble contrast agents used to enhance medical ultrasound imaging. This study sought to characterize the dynamics of this interaction by direct visual observation of microbubbles during insonification in vitro by a medical ultrasound imaging system. Video microscopy was used to observe air-filled sonicated albumin microspheres adsorbed to a solid support during insonation. Deflation was not observed at lowest transmit power settings. At higher intensities, gas left the microparticle gradually, apparently dissolving into the surrounding medium. Deflation was slower for higher microsphere surface densities. Intermittent ultrasound imaging (0.5 Hz refresh rate) caused slower deflation than continuous imaging (33 Hz). Higher concentrations of microbubbles, lower ultrasound transmit power settings, and intermittent imaging each can reduce the rate of destruction of microspheres resulting from medical ultrasound insonation.


Prenyltransferase from Saccharomyces cerevisiae. Purification to homogeneity and molecular properties.
Prenyltransferase (EC 126.96.36.199) has been purified to homogeneity from the supernatant fraction of yeast by ammonium sulfate fractionation, diethylaminoethyl-cellulose and hydroxylapatite chromatography, and column isoelectric focusing techniques. The active enzyme from isoelectric focusing columns emerged as a single symmetrical peak with specific activities 15- to 35-fold higher than previously reported preparations. The enzyme was found to be homogeneous by continuous polyacrylamide gel electrophoresis at pH 8.4 and discontinuous polyacrylamide gel electrophoresis at pH 6.9 as well as sodium dodecyl sulfate polyacrylamide electrophoresis at pH 7.0. By means of gel chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis, the protein was shown to be a dimer with a molecular weight of 84,000 plus or minus 10%. The isoelectric point of the enzyme was determined to be 5.3. The enzyme synthesizes farnesyl and geranylgeranyl pyrophosphates from dimethylallyl, geranyl, and farnesyl pyrophosphates. Michaelis constants for the enzyme were 4, 8, and 14 mu M for isopentenyl, dimethylallyl, and geranyl pyrophosphates, respectively.


Brine available two-dimensional nano-architectonics of fluorescent probe based on phosphate doped ZIF-L for detection of Fe3.
Herein, we propose a simple and effective strategy for designing a zeolitic imidazolate frameworks (ZIFs) fluorescent probe with a two-dimensional leaf-like structure. By doping ZIF-L with phosphate, we developed a fluorescent probe for iron (Fe3+) in systems with high salinity. The fluorescence of P-ZIF-L was quenched effectively with the presence of Fe3+. The physicochemical structure, surface morphology, selectivity, stability and composition of the probe were investigated. Under optimized conditions, the fluorescent probe had a detection limit of 0.5 μM. Furthermore, the results that the probe exhibited desirable salt-tolerance and was suitable for determination of Fe3+ in brine water samples with satisfactory results.


Special Issue: Application of SERS for Nanomaterials.
Surface-enhanced Raman scattering (SERS) is now a relatively mature field of spectroscopy, with it having been almost 50 years since its first experimental demonstration [...].


Postsurgical treatment of epilepsy.
In people with localization-related epilepsy who do not respond well to medication and continue to have seizures despite having been evaluated and treated by an epilepsy specialist, current recommendations are to consider surgery as an alternative to continued trials of different antiepileptic drugs (AEDs).


Weighted gene co-expression network-based approach to identify key genes associated with anthracycline-induced cardiotoxicity and construction of miRNA-transcription factor-gene regulatory network.
Cardiotoxicity is a common complication following anthracycline chemotherapy and represents one of the serious adverse reactions affecting life, which severely limits the effective use of anthracyclines in cancer therapy. Although some genes have been investigated by individual studies, the comprehensive analysis of key genes and molecular regulatory network in anthracyclines-induced cardiotoxicity (AIC) is lacking but urgently needed. The present study integrating several transcription profiling datasets aimed to identify key genes associated with AIC by weighted correlation network analysis (WGCNA) and differentially expressed analysis (DEA) and also constructed miRNA-transcription factor-gene regulatory network. A total of three transcription profiling datasets involving 47 samples comprising 41 rat heart tissues and 6 human induced pluripotent stem cell-derived cardiomyocytes (hiPSCMs) samples were enrolled. The WGCNA and DEA with E-MTAB-1168 identified 14 common genes affected by doxorubicin administrated by 4 weeks or 6 weeks. Functional and signal enrichment analyses revealed that these genes were mainly enriched in the regulation of heart contraction, muscle contraction, heart process, and oxytocin signaling pathway. Ten (Ryr2, Casq1, Fcgr2b, Postn, Tceal5, Ccn2, Tnfrsf12a, Mybpc2, Ankrd23, Scn3b) of the 14 genes were verified by another gene expression profile GSE154603. Importantly, three key genes (Ryr2, Tnfrsf12a, Scn3b) were further validated in a hiPSCMs-based in-vitro model. Additionally, the miRNA-transcription factor-gene regulatory revealed several top-ranked transcription factors including Tcf12, Ctcf, Spdef, Ebf1, Sp1, Rcor1 and miRNAs including miR-124-3p, miR-195-5p, miR-146a-5p, miR-17-5p, miR-15b-5p, miR-424-5p which may be involved in the regulation of genes associated with AIC. Collectively, the current study suggested the important role of the key genes, oxytocin signaling pathway, and the miRNA-transcription factor-gene regulatory network in elucidating the molecular mechanism of AIC.


Prediction of response to anti-vascular endothelial growth factor treatment in diabetic macular oedema using an optical coherence tomography-based machine learning method.
To predict the anti-vascular endothelial growth factor (VEGF) therapeutic response of diabetic macular oedema (DME) patients from optical coherence tomography (OCT) at the initiation stage of treatment using a machine learning-based self-explainable system. A total of 712 DME patients were included and classified into poor and good responder groups according to central macular thickness decrease after three consecutive injections. Machine learning models were constructed to make predictions based on related features extracted automatically using deep learning algorithms from OCT scans at baseline. Five-fold cross-validation was applied to optimize and evaluate the models. The model with the best performance was then compared with two ophthalmologists. Feature importance was further investigated, and a Wilcoxon rank-sum test was performed to assess the difference of a single feature between two groups. Of 712 patients, 294 were poor responders and 418 were good responders. The best performance for the prediction task was achieved by random forest (RF), with sensitivity, specificity and area under the receiver operating characteristic curve of 0.900, 0.851 and 0.923. Ophthalmologist 1 and ophthalmologist 2 reached sensitivity of 0.775 and 0.750, and specificity of 0.716 and 0.821, respectively. The sum of hyperreflective dots was found to be the most relevant feature for prediction. An RF classifier was constructed to predict the treatment response of anti-VEGF from OCT images of DME patients with high accuracy. The algorithm contributes to predicting treatment requirements in advance and provides an optimal individualized therapeutic regimen.


Metformin use before COVID-19 vaccination and the risks of COVID-19 incidence, medical utilization, and all-cause mortality in patients with type 2 diabetes mellitus.
We designed this study to determine whether metformin use before COVID-19 vaccination influences the risk of COVID-19 infection, medical utilization, and mortality. We used the US collaborative network of TriNetX to identify 123,709 patients with type 2 diabetes mellitus fully vaccinated against COVID-19 between January 1, 2020, and November 22, 2022. The study selected 20,894 pairs of metformin users and nonusers by propensity score matching. The Kaplan-Meier method and Cox proportional hazards models were used to compare the risks of COVID-19 infection, medical utilization, and mortality between the study and control groups. No significant difference was noted between metformin users and nonusers in the risk of COVID-19 incidence (aHR = 1.02, 95% CI = 0.94-1.10). Compared to the control cohort, the metformin cohort exhibited a significantly lower risk of hospitalization (aHR = 0.85, 95% CI = 0.81-0.89), critical care services (aHR = 0.81, 95% CI = 0.70-0.94), mechanical ventilation (aHR = 0.75, 95% CI = 0.60-0.95), and mortality (aHR = 0.75, 95% CI = 0.63-0.89). The subgroup analyses and sensitivity analysis showed similar results. The present study showed that metformin use before COVID-19 vaccination could not reduce COVID-19 incidence; however, it was associated with significantly lower risks of hospitalization, intensive care service, mechanical ventilation, and mortality in fully vaccinated type 2 diabetes mellitus patients.


Nitric oxide reduces the thermogenic changes induced by lateral hypothalamic lesion.
The experiment described here tests the effect of intracerebroventricular (icv) injection of nitric oxide (NO) precursors, such as L-arginine (L-arg) and nitroprusside (NP), on the thermogenic changes induced by lesion of the lateral hypothalamus (LH). The firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures (TIBAT and TC) were monitored in urethane-anaesthetized male Sprague-Dawley rats lesioned in the LH. These variables were measured before and after an icv injection of 4 mumol L-arg or 400 nmol NP. The same variables were also monitored in: a) lesioned rats with icv administration of saline; b) sham-lesioned animals with icv injection of L-arg or NP; c) sham-lesioned rats with icv injection of saline. The results show that L-arg or NP injection reduces the increases in firing rate. TIBAT and TC induced by LH lesion. These findings suggest that NO plays a key role in the thermogenic changes following LH lesion.


Biofilm control with natural and genetically-modified phages.
Bacteriophages, as the most dominant and diverse entities in the universe, have the potential to be one of the most promising therapeutic agents. The emergence of multidrug-resistant bacteria and the antibiotic crisis in the last few decades have resulted in a renewed interest in phage therapy. Furthermore, bacteriophages, with the capacity to rapidly infect and overcome bacterial resistance, have demonstrated a sustainable approach against bacterial pathogens-particularly in biofilm. Biofilm, as complex microbial communities located at interphases embedded in a matrix of bacterial extracellular polysaccharide substances (EPS), is involved in health issues such as infections associated with the use of biomaterials and chronic infections by multidrug resistant bacteria, as well as industrial issues such as biofilm formation on stainless steel surfaces in food industry and membrane biofouling in water and wastewater treatment processes. In this paper, the most recent studies on the potential of phage therapy using natural and genetically-modified lytic phages and their associated enzymes in fighting biofilm development in various fields including engineering, industry, and medical applications are reviewed. Phage-mediated prevention approaches as an indirect phage therapy strategy are also explored in this review. In addition, the limitations of these approaches and suggestions to overcome these constraints are discussed to enhance the efficiency of phage therapy process. Finally, future perspectives and directions for further research towards a better understanding of phage therapy to control biofilm are recommended.


Toxic neuropsychiatric effects of digoxin at therapeutic serum concentrations.
Serum digoxin concentrations can mislead psychiatric consultants. Two patients with therapeutic digoxin concentrations were seen for neuropsychiatric disorders that cleared rapidly once digoxin was discontinued.


Long-term weight loss in a 24-month primary care-anchored telehealth lifestyle coaching program: Randomized controlled trial.
Long-term weight loss can reduce the risk of type 2 diabetes for people living with obesity and reduce complications for patients diagnosed with type 2 diabetes. We investigated whether a telehealth lifestyle-coaching program (Liva) leads to long-term (24 months) weight loss compared to usual care. In a randomized controlled trial, n = 340 participants living with obesity with or without type 2 diabetes were enrolled and randomized via an automated computer algorithm to an intervention group (n = 200) or to a control group (n = 140). The telehealth lifestyle-coaching program comprised of an initial one-hour face-to-face motivational interview followed by asynchronous telehealth coaching. The behavioural change techniques used were enabled by individual live monitoring. The primary outcome was a change in body weight from baseline to 24 months. Data were assessed for n = 136 participants (40%), n = 81 from the intervention group and n = 55 from the control group, who completed the 24-month follow-up. After 24 months mean body weight and body mass index were reduced significantly for completers in both groups, but almost twice as much was registered for those in the intervention group which was not significant between groups -4.4 (CI -6.1; -2.8) kg versus -2.5 (CI -3.9; -1.1) kg, P = 0.101. Haemoglobin A1c was significantly reduced in the intervention group -3.1 (CI -5.0; -1.2) mmol/mol, but not in the control group -0.2 (CI -2.4; -2.0) mmol/mol without a significant between group difference (P = 0.223). Low completion was partly due to coronavirus disease 2019. Telehealth lifestyle coaching improve long-term weight loss (> 24 months) for obese people with and without type 2 diabetes compared to usual care.


Helping the parents of the dying child: an Israeli experience.
This small sample study attempted to define the problems families faced when their child was dying. The longitudinal approached allowed us to identify patterns of parental response and to identify patterns of nursing intervention that the parents found helpful. The results of the study have helped us teach other nurses how to more successfully work with these families.


Invisible social grouping facilitates the recognition of individual faces.
Emerging evidence suggests a specialized mechanism supporting perceptual grouping of social entities. However, the stage at which social grouping is processed is unclear. Through four experiments, here we showed that participants' recognition of a visible face was facilitated by the presence of a second facing (thus forming a social grouping) relative to a nonfacing face, even when the second face was invisible. Using a monocular/dichoptic paradigm, we further found that the social grouping facilitation effect occurred when the two faces were presented dichoptically to different eyes rather than monocularly to the same eye, suggesting that social grouping relies on binocular rather than monocular neural channels. The above effects were not found for inverted face dyads, thereby ruling out the contribution of nonsocial factors. Taken together, these findings support the unconscious influence of social grouping on visual perception and suggest an early origin of social grouping processing in the visual pathway.


CFTR modulator therapies - Effect on life expectancy in people with cystic fibrosis.
CFTR modulators have dramatically changed the clinical course of CF in those fortunate enough to receive them. Inevitably, randomised controlled trials during the development of these drugs are too short to use mortality as an outcome. Evidence for their effect on life expectancy are best gained from real world registry studies specifically looking at mortality, but these are only available for ivacaftor to date. Therefore, indirect evidence must be obtained by looking at outcomes known to affect mortality and seeing the effect of these drugs on those outcomes.


Factors Associated with Self-regulation in a Nationally Representative Sample of Children Ages 3-5 Years: United States, 2016.
The aim of the present study was to describe self-regulation (the ability to influence or control one's thoughts or behavior in response to situational demands and social norms) in children ages 3-5 years using a nationally representative sample and examine risk and protective factors to identify opportunities to support children and families. Using a cross-sectional design, we examined data from a parent-reported pilot measure of self-regulation from the 2016 National Survey of Children's Health (NSCH). We compared U.S. children aged 3-5 years who were described by parents as "on track" with self-regulation development with children who were not. In addition, we described how health care and developmental services, community, family, and child health and development factors are associated with children's self-regulation. The majority of children (4 of 5) were described by their parents to be developmentally on track with self-regulation. Compared to children described as not on track, children described as on track more often lived in financially and socially advantaged environments and less often experienced family adversity. They also had other positive health and development indicators, whether or not they were receiving developmental services. However, only half of children not on track received developmental surveillance, and only 1 in 4 children described as not on track received educational, mental health, or developmental services. The findings are a step towards using self-regulation as an indicator of healthy child development and as a potential strategy to identify groups of children who may need additional support.


On the molecular mechanisms for the highly procoagulant pattern of C6 glioma cells.
That there is a correlation between cancer and procoagulant states is well-known. C6 glioma cell line was originally induced in random-bred Wistar-Furth rats and is morphologically similar to glioblastoma multiforme, the most common aggressive glioma resistant to therapeutic interventions. In this study we analyzed the molecular mechanisms responsible for the highly procoagulant properties of C6 glioma cells. The presence of tissue factor (TF) and phosphatidylserine (PS) in C6 cells was investigated by flow-cytometric and functional analyses. The assembly of extrinsic tenase, intrinsic tenase and prothrombinase complexes on these cells was studied using enzymatic assays employing plasma or purified proteins. TF was identified by flow-cytometric and functional [factor (F) Xa formation in the presence of cells and FVIIa] assays. Alternatively, conversion of FX into FXa was also observed in the presence of C6 cells, FIXa and FVIIIa. This effect was both cell- and FVIIIa-dependent, being consistent with formation of the intrinsic tenase complex. C6 cells were also able to activate prothrombin in the presence of FXa and FVa, thus supporting formation of the prothrombinase complex. This ability was similar to positive controls performed with PS-containing vesicles. Accordingly, exposure of PS on C6 cells was demonstrated by flow cytometry employing specific anti-PS antibodies. In addition, annexin V, which blocks PS binding sites, inhibited FX and prothrombin conversion by their respective C6-assembled activating complexes. C6 glioma cells support all procoagulant reactions leading to robust thrombin formation. This ability results from concomitant TF exposure and from the presence of the anionic lipid PS at the outer leaflet of cell membrane. Therefore, this animal cell line may be used to explore new aspects concerning the role of blood coagulation proteins in tumor biology, especially those affecting the central nervous system.


Racial Health Equity Plans in the 30 Largest US Cities.
Racial inequities in life expectancy vary significantly across US cities, with city-level gaps ranging from zero to more than 10 years. Given that these inequities are rooted in racism and maintained through social structures and policies, population-level solutions are needed. Local health departments (LHD) are well-situated to lead these types of changes. We conducted an environmental scan and document review of formal health plans of the LHDs with jurisdictions covering the 30 most populous US cities. We assessed the inclusion of equity priorities and specific and measurable equity goals. Secondary outcomes related to organizational structures, data, formal declarations, and other practices were also assessed. Data were collected between January and August 2022. The extent of focus on racial equity in the identified strategic health plans varied. Less than half of the cities with a formal public health plan (13 of 29) listed racial health equity as an area of focus. Only seven cities (all of which had a health plan focusing on racial health equity) had specific goals related to racial health equity. Twenty-five LHDs provided local data on racial health inequities. All but seven cities had declared racism a public health crisis. About half of the LHDs had positions or divisions focused on racial equity, or specified equity as an area of focus for Covid-19 efforts. These findings reveal that few large cities translate growing support for anti-racism into their formal planning. While most LHDs acknowledge (and provide data pointing to) gaps in racial health equity in their jurisdictions, more attention is needed to incorporate specific and measurable racial health equity goals into strategic plans, and provide adequate structure and resources to attain those goals.


[A search for site-specific type-II restriction endonucleases in streptomycetes].
Three Streptomycetes strains producing endonucleases of restriction of II type have been found using the modified method of Belavin.


Altered RNA transport without derepression in a rat kidney tumor induced by dimethylnitrosamine.
RNA/DNA hybridization in the presence of competing RNA was used to study transcription and transport of RNA from the nucleus to the cytoplasm in a rat renal tumor induced by a single intraperitoneal injection of dimethylnitrosamine (DMN). Neither repression nor derepression of transcription of repetitive DNA can be detected in this tumor, but transcripts of all active families of such sequences are found in the tumor cytoplasm. This is the pattern of RNA change found in the chemically-induced hepatocellular carcinomas and contrasts with the pattern of virus-induced renal tumors in which both altered transport and derepression of host repetitive sequences have been demonstrated. The alteration of RNA transport is nearly complete in the kidney only two days after the above treatment, but there is no such alteration detectable in the kidney after nine days of feeding a liver carcinogen which is not carcinogenic to kidneys. This data supports the significance and specificity of the loss of ability to restrict certain RNA sequences to the nucleus early during malignant transformation.


Effects of topical application of clonidine cream on pain behaviors and spinal Fos protein expression in rat models of neuropathic pain, postoperative pain, and inflammatory pain.
Clonidine can effectively reduce pain and/or hypersensitivity. However, the antihypersensitivity effects of clonidine topically applied in cream (CC) have not been investigated. The authors evaluated effects of topical application of CC on pain behaviors and spinal Fos-like immunoreactivity in rats with hypersensitivity. Clonidine (30, 100, and 300 microg/g) was prepared in a cream base. In rat models of neuropathic pain, inflammatory pain, and postoperative pain, the authors evaluated effects of CC (0.1 g), topically applied onto the plantar surface of the injured or uninjured paw, on thermal hyperalgesia and mechanical allodynia to von Frey filaments. The authors also evaluated effects of CC on lumbar spinal Fos-like immunoreactivity. In neuropathic rats, CC applied onto the injured paw reduced thermal hyperalgesia and mechanical allodynia dose dependently, whereas CC applied onto the uninjured paw had no effect. The antihypersensitivity effects of CC were antagonized by intraperitoneal yohimbine (10 mg/kg). Further, CC reduced Fos-like immunoreactivity in neuropathic rats. In contrast, CC in a single dose had no effects on hyperalgesia, allodynia, or Fos-like immunoreactivity in rats with inflammatory or postoperative pain. In rats with postoperative pain, CC repeatedly applied for 6 days reduced thermal hyperalgesia, but not mechanical allodynia, in the postoperative days, whereas it had no effects on hyperalgesia or allodynia in those with inflammatory pain. Topical CC in concentrations examined significantly reduced hypersensitivity and lumbar spinal Fos-like immunoreactivity in rats with neuropathic pain, probably through activation of peripherally located alpha2 adrenoceptors. However, CC was only partially effective and totally ineffective in rats with postoperative pain and inflammatory pain, respectively.


Promotion of NAD+ recycling by the hypoxia-induced shift in the lactate dehydrogenase isozyme profile reduces the senescence of human bone marrow-derived endothelial progenitor cells.
Expansion of bone marrow-derived endothelial progenitor cells (EPCs) in vitro to obtain required cell numbers for therapeutic applications faces the challenge of growing cell senescence under the traditional normoxic culture condition. We previously found that 1% O2 hypoxic culture condition is favorable for reducing senescence of EPCs, but the mechanisms underlying the favorability are still unclear. Here, we found that, compared with normoxia, hypoxia induced a shift in lactate dehydrogenase (LDH) isozyme profile, which manifested as decreased LDH2 and LDH1 and increased LDH5, LDH4 and total LDHs. Moreover, under hypoxia, EPCs presented higher LDH activity, which could promote the conversion of pyruvate to lactate, as well as a higher level of NAD+, Bcl2 interacting protein 3 (BNIP3) expression and mitophagy. Additionally, under hypoxia, knock-down of the LDHA subunit increased the LDH2 and LDH1 levels and knock-down of the LDHB subunit increased the LDH5 level, while the simultaneous knock-down of LDHA and LDHB reduced total LDHs and NAD+ level. Inhibition of NAD+ recycling reduced BNIP3 expression and mitophagy and promoted cell senescence. Taken together, these data demonstrated that 1% O2 hypoxia induces a shift in the LDH isozyme profile, promotes NAD+ recycling, increases BNIP3 expression and mitophagy, and reduces EPC senescence. Our findings contribute to a better understanding of the connection between hypoxic culture conditions and the senescence of bone marrow-derived EPCs and provide a novel strategy to improve in vitro expansion of EPCs.


Comparison of the AVPU Scale and the Pediatric GCS in Prehospital Setting.
The pediatric Glasgow coma scale (pGCS) is a consciousness score that, although widely applied, requires skill to apply. The AVPU scale uses four simple categories (Alert; Verbal response; response to Pain; Unresponsive), but has not been studied in a large pediatric population. We compared the performance of the AVPU and pGCS scales in a large pediatric cohort in an acute, prehospital setting. In a six-month-long prospective cohort study, AVPU and pGCS scores were determined by emergency physicians in children less than 10 years of age at their first prehospital encounter. We included 302 children (median age 2.3 years) with a broad spectrum of diagnoses. Data were complete for 287 children. AVPU and pGCS scores showed good a correlation in the extreme categories A and U (positive predictive values of 98% and 100%, respectively). Corresponding pGCS scores for each AVPU category were as follows: 11-15 for A; 5-15 for V; 4-12 for P; and 3-5 for U. The positive predictive value to detect patients with pGCS ≥ 8 for AVPU category V was 100%. We demonstrated good correlation of simple and fast consciousness AVPU scoring to the standard pGCS in a large cohort of pediatric patients in a prehospital setting. The AVPU category "V" identifies patients with a pGCS of or exceeding 8 and, therefore, identifies children at low risk requiring more invasive procedures or intensive care treatment. Glasgow coma scale (GCS); Alert-verbal-pain-unresponsive-score; AVPU-score; consciousness assessment; children, pediatric emergency.


The mdx Mutation in the 129/Sv Background Results in a Milder Phenotype: Transcriptome Comparative Analysis Searching for the Protective Factors.
The mdx mouse is a good genetic and molecular murine model for Duchenne Muscular Dystrophy (DMD), a progressive and devastating muscle disease. However, this model is inappropriate for testing new therapies due to its mild phenotype. Here, we transferred the mdx mutation to the 129/Sv strain with the aim to create a more severe model for DMD. Unexpectedly, functional analysis of the first three generations of mdx129 showed a progressive amelioration of the phenotype, associated to less connective tissue replacement, and more regeneration than the original mdxC57BL. Transcriptome comparative analysis was performed to identify what is protecting this new model from the dystrophic characteristics. The mdxC57BL presents three times more differentially expressed genes (DEGs) than the mdx129 (371 and 137 DEGs respectively). However, both models present more overexpressed genes than underexpressed, indicating that the dystrophic and regenerative alterations are associated with the activation rather than repression of genes. As to functional categories, the DEGs of both mdx models showed a predominance of immune system genes. Excluding this category, the mdx129 model showed a decreased participation of the endo/exocytic pathway and homeostasis categories, and an increased participation of the extracellular matrix and enzymatic activity categories. Spp1 gene overexpression was the most significant DEG exclusively expressed in the mdx129 strain. This was confirmed through relative mRNA analysis and osteopontin protein quantification. The amount of the 66 kDa band of the protein, representing the post-translational product of the gene, was about 4,8 times higher on western blotting. Spp1 is a known DMD prognostic biomarker, and our data indicate that its upregulation can benefit phenotype. Modeling the expression of the DEGs involved in the mdx mutation with a benign course should be tested as a possible therapeutic target for the dystrophic process.


The novel HLA-A*02:07:23 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.
HLA-A*02:07:23 differs from HLA-A*02:07:01:01 by one nucleotide in exon 2.


iPiDA-sHN: Identification of Piwi-interacting RNA-disease associations by selecting high quality negative samples.
As a large group of small non-coding RNAs (ncRNAs), Piwi-interacting RNAs (piRNAs) have been detected to be associated with various diseases. Identifying disease associated piRNAs can provide promising candidate molecular targets to promote the drug design. Although, a few computational ensemble methods have been developed for identifying piRNA-disease associations, the low-quality negative associations even with positive associations used during the training process prevent the predictive performance improvement. In this study, we proposed a new computational predictor named iPiDA-sHN to predict potential piRNA-disease associations. iPiDA-sHN presented the piRNA-disease pairs by incorporating piRNA sequence information, the known piRNA-disease association network, and the disease semantic graph. High-level features of piRNA-disease associations were extracted by the Convolutional Neural Network (CNN). Two-step positive-unlabeled learning strategy based on Support Vector Machine (SVM) was employed to select the high quality negative samples from the unknown piRNA-disease pairs. Finally, the SVM predictor trained with the known piRNA-disease associations and the high quality negative associations was used to predict new piRNA-disease associations. The experimental results showed that iPiDA-sHN achieved superior predictive ability compared with other state-of-the-art predictors.


Characterization of enzymatic deficiencies of branched chain amino-acid catabolism in human fibroblasts by genetic complementation.
Leucine and Isoleucine metabolism in cultured skin fibroblasts from patients with leucinosis, beta-Ketothiolase deficiency, propionic, methylmalonic and isovaleric acidemia, was compared with that in normal fibroblasts. A simple assay was developed using (U14C) Isoleucine and (U14C) Leucine as substrates. Radioactive incorporation into protein aminoacids were measured. The (U14C) branched chain aminoacid incorporation into proteins provides an estimation of the protein synthesis and the incorporation ratio (14C) Aspartate + (14C) Glutamate/(14C) branched chain aminoacid, measures the integrity of the metabolic pathway. Complementation tests permits to characterize the genetic defect. The incorporation ratio was significantly decreased in blocked pathways, namely in leucinosis and isovaleric acidemia in the presence of (U14C) Leucine and in Leucinosis, beta-Ketothiolase deficiency, propionic and methylmalonic acidemia in the presence of (U14C) Isoleucine. There was a significant restoration of activity in mutant strains with distinct genetic defects after polyethylene-glycol fusion. This assay provides a valuable tool to screen for enzymatic deficiencies of branched chain aminoacid catabolism.


Maintenance of replication patterns in human-mouse hybrids retaining only one human chromosome.
The time of termination of DNA replication of human chromosomes in human-mouse hybrids retaining only one human chromosome was analyzed. Hybrids between SV40-transformed human skin fibroblasts and mouse peritoneal macrophages were used for these studies. Data obtained from hybrids containing only human chromosome 7 or 17 were compared with data from related hybrids containing additional human chromosomes. When either human chromosome 7 or 17 was present alone, it terminated replication at the same stage of the S phase as in hybrids in which other human chromosomes were present (relative to the time of termination of replication of the mouse chromosomes). In comparing the hybrids containing single human chromosomes, it was found that chromosome 17 terminated replication much earlier than chromosome 7. Therefore, the relationship between the replication times of these chromosomes normally observed in human cells was maintained in the hybrids in the absence of all other human chromosomes. The results also indicate that the presence of SV40 gene sequences in chromosomes 7 and 17 did not alter the relative times of termination of replication of those chromosomes.


Captopril administered every three hours in difficult-to-control hypertension.
The renovascular hypertension of an elderly patient, which was controlled initially with standard-dose therapy with captopril, later responded only to 75 mg given every 3 h without side effects. Changeover to another class of antihypertensives, as is recommended in recalcitrant cases, was not needed. Convenient maintenance therapy with lisinopril (10 mg twice daily) has kept blood pressure under control for a year.


Acquisition of classical conditioning without cerebellar cortex.
The left cerebellar cortex was surgically aspirated in rabbits who were then subsequently trained for classical conditioning of the nictitating membrane. All rabbits were trained sequentially on both eyes. Rabbits with the lesion confined to the cerebellar cortex were able to learn with the eye ipsilateral to the lesion although it took many times longer than reported for either naive rabbits or for rabbits first trained on the unlesioned, contralateral side. Rabbits with lesions that included the cerebellar cortex and the cerebellar interpositus nucleus did not learn with the eye ipsilateral to the lesion. Learning with the eye contralateral to either type of lesion was always very rapid. It is now clear on the basis of this and previous studies that cerebellar cortex, unlike the cerebellar interpositus nucleus, is not essential for acquisition or relearning/retention of classical conditioning. However, cerebellar cortex normally plays an important role since acquisition of classical eyeblink conditioning is prolonged and of poor quality in its absence.


Prevalence and correlates of depressive symptoms among high school adolescent girls in southern Uganda.
In sub-Saharan Africa (SSA), adolescent girls and young women are three times more likely than boys to have depressive disorders. Understanding adolescents' unique and common vulnerabilities and protective factors is essential for the development of appropriate interventions and programming focused on child and adolescent mental health. This paper examines the prevalence and predictors of depressive symptoms among high school adolescent girls in southern Uganda. Baseline data from a longitudinal cluster randomized study involving 1260 adolescent girls (14-17 years), recruited from 47 secondary schools were utilized. Depressive symptoms were estimated using the 21-item Beck's Depression Inventory. Hierarchical linear regression modelling was utilized to estimate key predictors of depressive symptoms among adolescent girls. Of the total sample, 16.35% (n = 206) reported severe depressive symptoms and almost one in every three adolescent girls interviewed (29.68%, n = 374) reported moderate symptoms. These symptoms were more prevalent among older adolescents (16 years and above). In addition, family relationships, social support, as well as measures of psychological wellbeing (self-concept and self-esteem) were all associated with lower levels of depressive symptoms. Hopelessness was associated with higher levels of depressive symptoms among adolescent girls. Findings from this study indicate a high prevalence of depressive symptoms, especially among older adolescent girls. In addition, family support factors and adolescents' psychological wellbeing were associated with low levels of depressive symptoms -pointing to the need to strengthen family functioning and adolescent's psychological wellbeing to mitigate risks. Taken together, findings support increasing calls for early screening and detection of depressive symptoms to facilitate timely referral to care and treatment. Findings may also inform the development and incorporation of gender-specific mental health components in programming targeting adolescent girls, in low-resource communities in SSA. This trial was prospectively registered with ClinicalTrials.gov (registration number: NCT03307226 ) on 11 October 2017.


Insulin-like growth factor binding protein 7 modulates estrogen-induced trophoblast proliferation and invasion in HTR-8 and JEG-3 cells.
Previous research has reported that IGFBP7 functions as a tumor suppressor gene in different tumors, but its role in the trophoblast has not been elucidated. In this research, we studied the regulation mechanism of IGFBP7 in trophoblast proliferation and invasion in HTR-8 and JEG-3 cell lines. We found that IGFBP7 was abundantly expressed in normal human syncytiotrophoblast tissue samples but that this was lacking in hydatidiform moles. The proliferation and invasion capacities of HTR-8 and JEG-3 cells were significantly inhibited by recombinant IGFBP7. Estrogen (E2) stimulated the expression of IGFBP7 at a concentration of 5-10 ng/mL. This stimulation was inhibited by the estrogen receptor antagonist Fulvestrant (ICI182.780) and a TGFβ-neutralizing antibody. In conclusion, our data reveals that estrogen stimulates the expression of IGFBP7 through estrogen receptors and TGFβ. The expression of IGFBP7 could be stimulated by TGFβ in a dose-dependent manner and inhibited by IFNγ in HTR-8 and JEG-3 cells. IGFBP7 could also inhibit the phosphorylation of ERK and the expression of PCNA, MMP2 and MMP9 in HTR-8 and JEG-3 cells. These findings suggest that IGFBP7 is a key regulator of E2-induced trophoblast proliferation and invasion.


A Case of Wallenberg's Syndrome Presenting with Spontaneous Thrombosis of a Vertebral Artery Aneurysm.
Complete spontaneous thrombosis of intracranial aneurysms is uncommon. Although this type of thrombosis is largely asymptomatic, in rare cases it can be accompanied by parent artery occlusion and ischemic stroke. There are limited reports of complete thrombosis of an unruptured aneurysm of the internal carotid artery and middle cerebral artery. Furthermore, there are no reports of occlusion of the vertebral artery caused by thrombosis of an aneurysm. The mechanisms of spontaneous thrombosis are not established. However, aneurysm morphology, arteriosclerosis, and stagnation of aneurysm flow have been suggested. Herein, we present a novel case of Wallenberg's syndrome caused by a fusiform aneurysm in which complete thrombosis of the proximal vertebral artery occurred. We discuss the mechanisms of thrombosis caused by an unruptured aneurysm, which may be useful for managing such patients who present with transient ischemic attacks.


Rare variants found in clinical gene panels illuminate the genetic and allelic architecture of orofacial clefting.
Orofacial clefts (OFCs) are common birth defects including cleft lip, cleft lip and palate, and cleft palate. OFCs have heterogeneous etiologies, complicating clinical diagnostics because it is not always apparent if the cause is Mendelian, environmental, or multifactorial. Sequencing is not currently performed for isolated or sporadic OFCs; therefore, we estimated the diagnostic yield for 418 genes in 841 cases and 294 controls. We evaluated 418 genes using genome sequencing and curated variants to assess their pathogenicity using American College of Medical Genetics criteria. 9.04% of cases and 1.02% of controls had "likely pathogenic" variants (P < .0001), which was almost exclusively driven by heterozygous variants in autosomal genes. Cleft palate (17.6%) and cleft lip and palate (9.09%) cases had the highest yield, whereas cleft lip cases had a 2.80% yield. Out of 39 genes with likely pathogenic variants, 9 genes, including CTNND1 and IRF6, accounted for more than half of the yield (4.64% of cases). Most variants (61.8%) were "variants of uncertain significance", occurring more frequently in cases (P = .004), but no individual gene showed a significant excess of variants of uncertain significance. These results underscore the etiological heterogeneity of OFCs and suggest sequencing could reduce the diagnostic gap in OFCs.


Validation of an Automated Wearable Camera-Based Image-Assisted Recall Method and the 24-h Recall Method for Assessing Women's Time Allocation in a Nutritionally Vulnerable Population: The Case of Rural Uganda.
Accurate data are essential for investigating relationships between maternal time-use patterns and nutritional outcomes. The 24 h recall (24HR) has traditionally been used to collect time-use data, however, automated wearable cameras (AWCs) with an image-assisted recall (IAR) may reduce recall bias. This study aimed to evaluate their concurrent criterion validity for assessing women's time use in rural Eastern Ugandan. Women's (n = 211) time allocations estimated via the AWC-IAR and 24HR methods were compared with direct observation (criterion method) using the Bland-Altman limits of agreement (LOA) method of analysis and Cronbach's coefficient alpha (time allocation) or Cohen's κ (concurrent activities). Systematic bias varied from 1 min (domestic chores) to 226 min (caregiving) for 24HR and 1 min (own production) to 109 min (socializing) for AWC-IAR. The LOAs were within 2 h for employment, own production, and self-care for 24HR and AWC-IAR but exceeded 11 h (24HR) and 9 h (AWC-IAR) for caregiving and socializing. The LOAs were within four concurrent activities for 24HR (-1.1 to 3.7) and AWC-IAR (-3.2 to 3.2). Cronbach's alpha for time allocation ranged from 0.1728 (socializing) to 0.8056 (own production) for 24HR and 0.2270 (socializing) to 0.7938 (own production) for AWC-IAR. For assessing women's time allocations at the population level, the 24HR and AWC-IAR methods are accurate and reliable for employment, own production, and domestic chores but poor for caregiving and socializing. The results of this study suggest the need to revisit previously published research investigating the associations between women's time allocations and nutrition outcomes.


Sigmoid adenocarcinoma with metastases to the kidney: Report of a rare case and review of the literature.
Distant metastases from colorectal cancer (CRC) most frequently spread to the liver and lungs. CRC metastasis to the kidney is extremely rare and may be generally associated with an unfavorable prognosis. Thus, patients with metastatic CRC and kidney metastasis are a diagnostic and therapeutic challenge. The present study reported the case of a 42-year-old male with a local recurrence of CRC following sigmoid resection with partial mesorectal excision, which had infiltrated the urinary bladder, requiring partial resection of the urinary bladder wall. After 4 years, the patient developed a recurrent tumor localized in the upper pole of the left kidney and underwent left nephrectomy. The patient remained disease-free 6 months after the surgery.


Bend but don't break: Prioritization protects working memory from displacement but leaves it vulnerable to distortion from distraction.
Perceptual distraction distorts visual working memory representations. Previous research has shown that memory responses are systematically biased towards passively viewed visual distractors that are similar to the memoranda. However, it remains unclear whether the prioritization of one working memory representation over another reduces the impact of perceptual distractors. We designed a study with five different types of visual distraction that varied in engagement and found evidence for both subtle distortions and catastrophic failures of memory. Importantly, prioritization protected working memories from catastrophic loss (fewer "swap errors") but rendered them more vulnerable to distortion (greater attractive "biases" towards the distractor). Our findings demonstrate that prioritization does not simply protect working memory from any and all interference, but rather it reduces the likelihood of catastrophic disruption from perceptual distraction at the cost of an increased likelihood of distortion.


Platelet-rich fibrin combined with a particulate bone substitute versus guided bone regeneration in the damaged extraction socket: An in vivo study.
It has been proposed that platelet-rich fibrin (PRF) can be used to support bone regeneration during alveolar ridge augmentation. The aim of this study was to determine whether an approach utilizing PRF provides similar performance to the established guided bone regeneration (GBR) procedure. Two-wall defects were surgically created in beagle dogs and treated in three experimental groups: (i) a sticky bone (SB) substitute prepared using liquid PRF and deproteinized porcine bone mineral (DPBM); (ii) SB covered with solid PRF compressed into a membrane; and (iii) GBR performed using DPBM covered by a collagen membrane. Quantitative reverse-transcription polymerase chain reaction was applied to the specimen after 1 week of healing, and microcomputed tomography (micro-CT) and histological outcomes were analysed after 8 weeks of healing. Compared with GBR, PRF resulted in a moderate increase in the expression levels of osteoblast and osteoclast markers, osteocalcin, and calcitonin receptor. Moreover, PRF modestly increased angiogenesis and the inflammation markers vascular endothelial growth factor (VEGF) and IL-6. Micro-CT and histological analyses confirmed the expected increased alveolar ridge area, with no significant differences between the three groups. Consistently, graft consolidation, as indicated by new bone formation at the defect site, did not differ significantly between groups. The present results demonstrate that PRF-based approaches perform comparably to the established GBR procedure in terms of the consolidation of DPBM in two-wall alveolar defects.


Screening and characterization of β-galactosidase activity in lactic acid bacteria for the valorization of acid whey.
β-Galactosidase is an enzyme produced by some strains of lactic acid bacteria (LAB) commonly found in dairy products; however, industrial demand for these enzymes is still low. Acid whey (AW), a lactose-rich byproduct, has large output from cottage cheese and remains unexploited. The purpose of this study was to understand the production mechanism of β-galactosidase from LAB using AW as a culture medium. First, bioinformatics analysis was conducted on 15 species of LAB. Then, 24 strains were selected and inoculated in de Man, Rogosa, and Sharpe (MRS) broth and in AW medium to compare the bacterial kinetic growth and β-galactosidase production. Bacterial growth and total protein activity were measured using spectrophotometric techniques. β-Galactosidase activity was determined by 2 methods: following the hydrolysis of o-nitrophenyl-β-d-galactopyranoside and of 5-bromo-4-chloro-3-indoyl-β-d-galactopyranoside (X-gal) in tryptic soy agar plates. The relative expression of the β-galactosidase gene was performed using real-time quantitative PCR. Despite generally lower growth in AW, 18 strains showed higher β-galactosidase activity when grown in AW compared with MRS medium. The highest β-galactosidase activity in AW was in Lactobacillus helveticus strain OSU-PECh-4A, which showed almost 5 times higher activity than average. Analysis of 6 selected strains for expression of the bgal-620 gene found higher overexpression in AW than in MRS, regardless of specific β-galactosidase activity. Strains of LAB such as OSU-PECh-4A could valorize AW through the production of β-galactosidase (as an aid to lactose digestion) and production of prebiotic galactooligosaccharides.


Vertical and temporal distribution of nitrogen and phosphorus and relationship with their influencing factors in aquatic-terrestrial ecotone: a case study in Taihu Lake, China.
Vertical and temporal distributions of N and P in soil solution in aquatic-terrestrial ecotone (ATE) of Taihu Lake were investigated, and the relations among N, P, ORP (oxidation reduction potential), TOC, root system biomass and microorganism were studied. As a whole, significant declines in TN, NO3- -N, DON (dissolved organic nitrogen) and TP concentration in soil solution have occurred with increase of the depth, and reached their minima at 60 cm depth, except for NH4+ -N, which increased with depth. The concentration of TP increased gradually from spring to winter in the topsoil, the maximum 0.08 mg/L presented in the winter while the minimum 0.03 mg/L in spring. In the deeper layer, the concentration value of TP fluctuated little. As for the NO3- -N, its seasonal variation was significant at 20 cm depth, its concentration increased gradually from spring to autumn, and decreased markedly in winter. Vertical and temporal distribution of DON is contrary to that of NO3- -N. The results also show that the variation of N and P in the percolate between adjacent layers is obviously different. The vertical variation of TN, TP, NO3- -N, NH4+ -N and DON is significant, of which the variation coefficient of NO3- -N along the depth reaches 100.23%, the highest; while the variation coefficient of DON is 41.14%, the smallest. The results of correlation analysis show that the concentration of nitrogen and phosphorus correlate significantly with TOC, ORP, root biomass and counts of nitrifying bacteria. Most nutrients altered much from 20 to 40 cm along the depth. However, DON changed more between 60 and 80 cm. Results show that soil of 0-60 cm depth is active rhizoplane, with strong capability to remove the nitrogen and phosphorus in ATE. It may suggest that there exists the optimum ecological efficiency in the depth of above 60 cm in reed wetland. This will be very significant for ecological restoration and reestablishment.


[Binding of iron ions by shielding eye pigments of vertebrates and invertebrates--melanosomes and ommochromes].
Melanosomas of eye pigment epithelium tissue of vertebrates, synthetic DOPA-melanin and ommochromas from eye of invertebrates bind effectively bivalent iron ions. Constants of the binding process are calculated. Endogenic iron concentration in melanosomas of the frog eye pigment epithelium is determined. A conclusion is drawn that mechanism of antioxidation action of shielding eye pigments may include Fe2+ ion binding into inactive components.


Immortalization of murine microglial cells by a v-raf/v-myc carrying retrovirus.
A murine cell line (BV-2) has been generated by infecting primary microglial cell cultures with a v-raf/v-myc oncogene carrying retrovirus (J2). BV-2 cells expressed nonspecific esterase activity, phagocytic ability and lacked peroxidase activity. Such cells secreted lysozyme and, following appropriate stimulation, also interleukin 1 and tumor necrosis factor. Furthermore, BV-2 cells exhibited spontaneous anti-Candida activity and acquired tumoricidal activity upon treatment with interferon-gamma. Phenotypically, BV-2 cells resulted positive for MAC1 and MAC2 antigens, and negative for MAC3, glial fibrillary acidic protein (GFAP) and galactocerebroside (GC) antigens. Since BV-2 cells retain most of the morphological, phenotypical and functional properties described for freshly isolated microglial cells, we can conclude that J2 virus infection has resulted in the immortalization of active microglial cells.


Neutrophil responses to intravascular pneumococcal sonicate.
Leukopenia and pulmonary leukostasis are prominent features in patients succumbing to pneumococcal (PNC) infections. We examined mechanisms involved in recruitment of polymorphonuclear neutrophils (PMNs) into pulmonary capillaries and alveolae after PNC sonicate injection. We showed that by 15 min postinjection, PMN chemotactic activity was found in bronchoalveolar lavage (BAL) fluids and increased with time until the end point of the study at 90 min. Accompanying the increased chemotactic activity in BAL fluids was a decrease in circulating PMNs more pronounced in the femoral artery (FA) than the pulmonary artery (PA). Superoxide anion (O2-) production by peripheral PMNs was depressed following PNC sonicate injection, and comparison of FA and PA showed that FA PMNs produced less O2- than PA PMNs. PA PMNs also showed enhanced random migration when compared to the depressed random migration of FA PMNs. This study demonstrated that an intravascular challenge of PNC sonicate was associated with increased chemotactic activity for PMNs in BAL fluid. Fewer PMNs and altered PMN function resulted from passage through the pulmonary microvasculature after PNC sonicate injection.


Non-thermal plasma coupled with a wet scrubber for removing odorous VOC.
Odorous volatile organic compounds (VOCs) deteriorate the quality of life and affect human health. In this study, a process was developed to remove an odorous VOC using a combined non-thermal plasma (NTP) and wet scrubber (WS) system. The low removal efficiency of WSs and the large amount of ozone generated by NTP were resolved. Compared to the decomposition effects when using a WS and NTP separately, the NTP + WS system improved the removal efficiency of ethyl acrylate (EA) and significantly reduced ozone emissions. The maximum EA removal efficiency was 99.9%. Additionally, an EA removal efficiency of over 53.4% and a 100% ozone removal efficiency were achieved even at discharge voltages lower than 4.5 kV. Ozone catalysis was confirmed to occur in the NTP + WS system. Furthermore, we verified the removal of by-products such as residual ozone and formaldehyde, which is a representative organic intermediate of EA. This study demonstrates that the NTP + WS system is a green technology for removing odorous VOCs.


Upregulated expression of LncRNA nicotinamide nucleotide transhydrogenase antisense RNA 1 is correlated with unfavorable clinical outcomes in cancers.
The nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) is a long non-coding RNA aberrantly expressed in human malignancies. We aimed to analyze available data to evaluate the correlation between NNT-AS1 expression and cancer prognosis. Literature retrieval was performed by systematic searching related databases from inception to April 2, 2020. Studies regarding correlation between NNT-AS1 expression, survival outcomes and clinical characteristics of cancer patients were collected and pooled to calculate the the hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (95% CIs). Ten studies comprising 699 patients were included, all of which were conducted in China according to literature selection criteria. Overexpression of NNT-AS1 had a significant association with unfavorable overall survival (OS) (HR = 2.08, 95% CI: 1.84-2.36, P < 0.001). Stratified analysis showed that tumor type, sample size, follow-up months, and survival analysis approach did not change the predictive value of NNT-AS1 on OS. Furthermore, elevated NNT-AS1 level had significant association with distant metastasis (DM) (OR = 2.45, 95% CI: 1.39-4.30), lymph node metastasis (LNM) (OR = 3.92, 95% CI: 1.35-11.41), TNM stage (OR = 4.25, 95% CI: 1.71-10.56), and vascular invasion (OR = 3.98, 95% CI: 2.06-7.71), but was not associated with age and gender. The TCGA dataset further consistently showed that the NNT-AS1 expression was associated with poor OS and disease-free survival. High expression of NNT-AS1 is associated with unfavorable survival outcomes and poor clinicopathologic characteristics. However, large-cohort data and geographical studies are still needed to further validate the prognostic value of NNT-AS1 in cancers.


Anti-human platelet tetraspanin (CD9) monoclonal antibodies induce platelet integrin alphaIIbbeta3 activation in a Fc receptor-independent fashion.
This study characterized the activation of platelet integrin alphaIIbbeta3 induced by two anti-human platelet tetraspanin monoclonal antibodies (mAbs), HI117 and SJ9A4. Using 125I-labeled human fibrinogen(Fg), specific Fg binding to human platelets induced by HI117 and SJ9A4 was measured as indication of activation of platelet integrin alphaIIbbeta3 by the two mAbs. HI117 and SJ9A4 (10 microg/ml and 20 microg/ml) induced evident specific Fg binding to human platelets, suggesting that the two mAbs evoked activation of platelet integrin alphaIIbbeta3. Further study indicated that HI117 and SJ9A4 induced integrin alphaIIbbeta3 activation independent of platelet Fc-receptors, and that HI117 and SJ9A4-induced integrin alphaIIbbeta3 activation was inhibited by sphingosing, aspirin, apyrase, and/or PGI2. The anti-platelet tetraspanin (CD9) mAbs, HI117 and SJ9A4, can induce platelet integrin alphaIIbbeta3 activation independent of Fc-receptor. Three signaling pathways, i.e. thromboxane, secreted ADP, and cAMP pathways may be involved in the process, with protein kinase C activation presumably being the common step of the three pathways.


[Opsonins and erythrophagocytosis].
The author studied the capacity of granulocytes and reticular cells of rat bone marrow to phagocytize mouse red blood cells in the action of opsonins against them. A comparative assessment of phagocytosis of fresh and formaldehyde-treated mouse red blood cells was conducted. A moderate phagocytosis observed with the use of fresh erythrocytes and immune noninactivated rat serum was less pronounced when inactivated serum was used. No phagocytosis occurred with rat nonimmune serum. On the contrary, when formaldehyde-treated erythrocytes were used with the same sera phagocytosis was much stronger.


Standardisation and validation of an in-house quantitative real-time polymerase chain reaction (qPCR) assay for the diagnosis of Clostridioides difficile infection.
Clostridioides difficile is an emerging enteric pathogen that causes nosocomial diarrhoea in adults. The excessive cost of commercial molecular tests restricts the access of developing countries to its diagnosis. This study aimed to develop and validate in-house quantitative polymerase chain reaction (qPCR) targeting the C. difficile toxin B gene (tcdB) using two detection methodologies-SYBR Green and hydrolysis probes-for the diagnosis of C. difficile infection (CDI). Glutamate dehydrogenase (GDH) plus toxigenic culture was the standard reference diagnostic method. The SYBR Green method and hydrolysis probes were used to study 392 samples simultaneously to assess the diagnostic value of these real-time PCR assays in detecting CDI from clinical samples. The SYBR Green and hydrolysis probe assays showed 97.9% and 87.5% sensitivity; 99.1% and 100.0% specificity; 94.0% and 100.0% positive predictive value; 99.7% and 98.3% negative predictive value; and 99.0% and 98.5% accuracy, respectively. The two qPCR methodologies evaluated could offer an adequate tool as part of an algorithm in the laboratory diagnosis of CDI.


[Non-taxoid chemical constituents from leaves of Taxus mairei].
To study the non-taxoids in the leaves of Taxus mairei. The chemical constituents were isolated by chromatography and identified by spectral data. Five compounds, taxamairin A (1), taxamairin B (2), sciadopitysin (3), ( - ) matairesinol (4), ponasterone A (5) were isolated and identified. Compounds 3-5 were isolated from this plant for the first time, compounds 1 and 2 were isolated from the leaves of T. mairei for the first time.


Phenotypic and cytogenetic findings in eighty-two patients with ovarian failure--changing trends.
Eighty-two patients with primary ovarian failure were evaluated clinically and cytogenetically. Sex chromosome privations were present in 52 individuals (chromosomally incompetent ovarian failure [CIOF]). A normal chromosomal constitution was present in 30 individuals (chromosomally competent ovarian failure [CCOF]). Limited estrogenic function (menses) occurred in 11.5% of the CIOF group and 40% of the CCOF group. The phenotypic features of each group are detailed in relation to chromosomal constitution, stature, estrogenic ridge function, incidence of dysgenetic tumors, and cardiovascular renal malformations. The increasing percentage of patients with CCOF due to possible diverse etiologies is noted and discussed.


Risk factors for the development of renal failure following the surgical treatment of traumatic aortic rupture.
A retrospective study of 44 patients who were treated surgically for traumatic aortic rupture was undertaken to determine risk factors for the development of postoperative renal failure. Renal failure occurred in 11 of 41 patients (27%) eligible for analysis. The Pearson product-moment correlation showed no significant relationship between the occurrence of renal failure and the patient's age, injury severity score, initial blood pressure, or the interval between accident and thoracotomy. Renal failure was significantly correlated with cross-clamping only (r = .2751, p = .043). There was no relationship between renal failure and total cross-clamp times. The mortality rate was significantly higher for patients with renal failure.


Infliximab effects compared to conventional therapy in the management of retinal vasculitis in Behçet disease.
To assess the outcome of retinal vasculitis in patients with Behçet disease treated with infliximab compared to treatment with conventional therapy. Nonrandomized, retrospective comparative clinical study. Patients with Behçet disease with all four major criteria were included in this study. Patients had recurrent episodes of uveitis and retinal vasculitis. Thirty-three patients (Group 1) were treated with oral prednisone, cyclosporine, and azathioprine or methotrexate for a minimum period of three months. Ten patients (Group 2) who failed to respond to conventional therapy were given infliximab at a dose of 5 mg/kg in a single intravenous infusion on day 1 and every two weeks for a total of six doses. Patients were given the same treatment during each subsequent relapse. The main outcome measures were the number of relapses, visual outcome, and ocular complications. The mean follow-up period was 36 months in Group 1 and 30 months in Group 2. The mean number of relapses was significantly reduced and the duration of remission was longer in the infliximab therapy group compared to conventional therapy group (P < .0001). The visual acuity at 24 months follow-up was significantly better in patients treated with infliximab (Group 2) when compared to conventional therapy (Group 1) (P = .0059). Patients with Behçet disease had significant decrease in inflammation, improvement of visual acuity, and reduced ocular complications following infliximab when compared to conventional therapy. The number of relapses was less in the infliximab treatment group than the conventional therapy group.