Effects of cholera and pertussis toxins on prolactin stimulation of lactose synthesis and ornithine decarboxylase activity in mouse mammary gland explants.
Studies indicate that G proteins are likely involved in the signal transduction pathway for prolactin's stimulation of mitogenesis in Nb2 cells. In the mammary gland, little is known about the possible role of G proteins in the prolactin (PRL) stimulation of milk product synthesis. Therefore, the effects of cholera and pertussis toxin, enzymes that modify G protein activity, were tested on several actions of prolactin on mouse mammary tissue in culture. At concentration of 0.1-0.5 micrograms/ml, cholera toxin stimulated ornithine decarboxylase activity in a dose-response fashion; when tested in concert, cholera toxin and prolactin caused an additive response. Cholera toxin by itself did not affect the rate of lactose synthesis, but at concentrations above 0.5 micrograms/ml, it attenuated the magnitude of the prolactin stimulation of lactose synthesis. Pertussis toxin (0-0.5 micrograms/ml), both by itself and in concert with PRL, had no effect on ornithine decarboxylase activity. At concentrations of 25 ng/ml and above, pertussis toxin inhibited the PRL stimulation of lactose synthesis, whereas at 0.2 and 0.5 micrograms/ml, pertussis toxin abolished the PRL response. These observations suggest that a G protein, but not Gs, may be involved in prolactin's mechanism of signal transduction in the mouse mammary gland.


Current State of Anthrax Vaccines and Key R&D Gaps Moving Forward.
A licensed anthrax vaccine has been available for pre-exposure prophylaxis in the United States since 1970, and it was approved for use as a post-exposure prophylaxis, in combination with antibiotic treatment, in 2015. A variety of other vaccines are available in other nations, approved under various regulatory frameworks. However, investments in anthrax vaccines continue due to the severity of the threat posed by this bacterium, as both a naturally occurring pathogen and the potential for use as a bioweapon. In this review, we will capture the current landscape of anthrax vaccine development, focusing on those lead candidates in clinical development. Although approved products are available, a robust pipeline of candidate vaccines are still in development to try to address some of the key research gaps in the anthrax vaccine field. We will then highlight some of the most pressing needs in terms of anthrax vaccine research.


Attenuated in vitro effects of IFN-α, IL-2 and IL-12 on functional and receptor characteristics of peripheral blood lymphocytes in metastatic melanoma patients.
Considering tumor-induced suppression of lymphocytes the aim of this study was to investigate in vitro effects of IFN-α, IL-2, IL-12 and IL-18 as immunomodulating agents on the functional and receptor characteristics of peripheral blood lymphocytes (PBL) in metastatic melanoma (MM) patients compared to healthy controls (HC). In HC IFN-α, IL-2 and IL-12 enhanced mRNA level of perforin by inducing pSTAT-1 and pSTAT-5 signaling molecules. Additionally, the expression of NKG2D activating receptor and its DAP10 signaling molecule was upregulated by IL-2. Contrary to this, in MM patients only IL-2 by upregulating pSTAT-5 increased perforin-mediated cytotoxicity of lymphocytes. Furthermore, there was significantly negative correlation between the percentage of CD4+CD25bright+CD27+ regulatory T (Treg) cells and NK cell cytotoxicity, as well as the expression of NKG2D receptor on PBL in HC and MM patients. Therefore, the absence of IL-2 effect on the increase of NKG2D/DAP10 level in MM patients could be the consequence of the increased percentage of immunosuppressive CD4+CD25bright+CD27+ cells after this cytokine treatment in patients. However, in MM IL-12 significantly decreases the percentage of these inhibitory cells. Although IL-2 as a single agent has numerous side effects, it remains the important cytokine for PBL activation in melanoma immunotherapy. Additionally, the removal of Treg cells from patient PBL by IL-12 before in vitro stimulation with IL-2, may lead to the generation of more potent cytotoxic lymphocytes against tumor cells. Therefore, lymphocyte based therapy for MM patients should integrate not only the choice of appropriate immunostimulatory cytokine, but also the removal of inhibitory cells from tumor microenvironment.


Nature-Based Solution to Eliminate Cyanotoxins in Water Using Biologically Enhanced Biochar.
Climate change and high eutrophication levels of freshwater sources are increasing the occurrence and intensity of toxic cyanobacterial blooms in drinking water supplies. Conventional water treatment struggles to eliminate cyanobacteria/cyanotoxins, and expensive tertiary treatments are needed. To address this, we have designed a sustainable, nature-based solution using biochar derived from waste coconut shells. This biochar provides a low-cost porous support for immobilizing microbial communities, forming biologically enhanced biochar (BEB). Highly toxic microcystin-LR (MC-LR) was used to influence microbial colonization of the biochar by the natural lake-water microbiome. Over 11 months, BEBs were exposed to microcystins, cyanobacterial extracts, and live cyanobacterial cells, always resulting in rapid elimination of toxins and even a 1.6-1.9 log reduction in cyanobacterial cell numbers. After 48 h of incubation with our BEBs, the MC-LR concentrations dropped below the detection limit of 0.1 ng/mL. The accelerated degradation of cyanotoxins was attributed to enhanced species diversity and microcystin-degrading microbes colonizing the biochar. To ensure scalability, we evaluated BEBs produced through batch-scale and continuous-scale pyrolysis, while also guaranteeing safety by maintaining toxic impurities in biochar within acceptable limits and monitoring degradation byproducts. This study serves as a proof-of-concept for a sustainable, scalable, and safe nature-based solution for combating toxic algal blooms.


[Vaginal birth after cesarean section in light of international opinions].
The tendency of increasing cesarean section rate has drawn worldwide attention. The vaginal birth after cesarean section is a useful method to decrease cesarean section rate at defined cases. Retrospective overview of factors resulting successful vaginal birth, labor/induction's condition, criterias, short and long term benefits and consequences. Overview recommendations of international guidelines and publications' results concerned vaginal birth after cesarean section in "PubMed", "MEDLINE", "Cochrane" databases from 1996 to 2016. Reviewing results of recommendations and publications we can declare that statements are inconsistent, however the option of vaginal birth after cesarean section is appropriate for decrease complications and trend of increasing cesarean section rate. It would be important in our country to define a uniform recommendation regarding vaginal birth after cesarean section, with supporting evidence in obstetrical and gynecological practice. Orv Hetil. 2017; 158(30): 1168-1174.


Highly Flexible and Conductive Cellulose-Mediated PEDOT:PSS/MWCNT Composite Films for Supercapacitor Electrodes.
Recent improvements in flexible electronics have increased the need to develop flexible and lightweight power sources. However, current flexible electrodes are limited by low capacitance, poor mechanical properties, and lack of cycling stability. In this article, we describe an ionic liquid-processed supramolecular assembly of cellulose and 3,4-ethylenedioxythiophene for the formation of a flexible and conductive cellulose/poly(3,4-ethylenedioxythiophene) PEDOT:poly(styrene sulfonate) (PSS) composite matrix. On this base, multiwalled carbon nanotubes (MWCNTs) were incorporated into the matrix to fabricate an MWCNT-reinforced cellulose/PEDOT:PSS film (MCPP), which exhibited favorable flexibility and conductivity. The MCPP-based electrode displayed comprehensively excellent electrochemical properties, such as a low resistance of 0.45 Ω, a high specific capacitance of 485 F g-1 at 1 A g-1, and good cycling stability, with a capacity retention of 95% after 2000 cycles at 2 A g-1. An MCPP-based symmetric solid-state supercapacitor with Ni foam as the current collector and PVA/KOH gel as the electrolyte exhibited a specific capacitance of 380 F g-1 at 0.25 A g-1 and achieved a maximum energy density of 13.2 Wh kg-1 (0.25 A g-1) with a power density of 0.126 kW kg-1 or an energy density of 4.86 Wh kg-1 at 10 A g-1, corresponding to a high power density of 4.99 kW kg-1. Another kind of MCPP-based solid-state supercapacitor without the Ni foam showed excellent flexibility and a high volumetric capacitance of 50.4 F cm-3 at 0.05 A cm-3. Both the electrodes and the supercapacitors were environmentally stable and could be operated under remarkable deformation or high temperature without damage to their structural integrity or a significant decrease in capacitive performance. Overall, this work provides a strategy for the fabrication of flexible and conductive energy-storage films with ionic liquid-processed cellulose as a medium.


CRISPR-spacer integration reporter plasmids reveal distinct genuine acquisition specificities among CRISPR-Cas I-E variants of Escherichia coli.
Prokaryotes immunize themselves against transmissible genetic elements by the integration (acquisition) in clustered regularly interspaced short palindromic repeats (CRISPR) loci of spacers homologous to invader nucleic acids, defined as protospacers. Following acquisition, mono-spacer CRISPR RNAs (termed crRNAs) guide CRISPR-associated (Cas) proteins to degrade (interference) protospacers flanked by an adjacent motif in extrachomosomal DNA. During acquisition, selection of spacer-precursors adjoining the protospacer motif and proper orientation of the integrated fragment with respect to the leader (sequence leading transcription of the flanking CRISPR array) grant efficient interference by at least some CRISPR-Cas systems. This adaptive stage of the CRISPR action is poorly characterized, mainly due to the lack of appropriate genetic strategies to address its study and, at least in Escherichia coli, the need of Cas overproduction for insertion detection. In this work, we describe the development and application in Escherichia coli strains of an interference-independent assay based on engineered selectable CRISPR-spacer integration reporter plasmids. By using this tool without the constraint of interference or cas overexpression, we confirmed fundamental aspects of this process such as the critical requirement of Cas1 and Cas2 and the identity of the CTT protospacer motif for the E. coli K12 system. In addition, we defined the CWT motif for a non-K12 CRISPR-Cas variant, and obtained data supporting the implication of the leader in spacer orientation, the preferred acquisition from plasmids harboring cas genes and the occurrence of a sequential cleavage at the insertion site by a ruler mechanism.


Success rate of fractured teeth receiving modified crown lengthening surgery and restorations.
Whether to preserve a structurally compromised tooth or remove it is a dilemma often encountered by clinicians. The aim of this study was to assess the long-term success rate of fractured teeth preserved by modified crown lengthening surgery and restorations. Thirty-nine patients with a total of 45 fractured teeth who had received modified crown lengthening surgery were recruited and examined. Numbers of teeth lost were recorded, and the criteria for successful teeth were defined. Kaplan-Meier estimator was used to determine the success rate. Possible risk factors were compared between successful and unsuccessful groups by a Cox regression analysis to explore the potential predictors of failure with a significant level at α = 0.05. The mean ± SD of success time without considering variants was 6.2 ± 0.6 years (95% CI 5.1-7.7). The mean survival rates ± SD at 1.0-, 2.0-, 3.0-, 5.0-, 7.0-, and 9.0-year intervals was 97.8 ± 2.2%, 92.2 ± 4.4%, 72.8 ± 7.9%, 68.2 ± 8.6%, 60.7 ± 10.5%, and 40.4 ± 13.6%, respectively. Failure cases in teeth with poor plaque control and step-shaped fracture margin were significantly more than those with good plaque control and knife-shaped fracture margin (HR = 7.237, p = 0.011; HR = 15.399, p = 0.006; respectively). Fractured teeth treated with modified crown lengthening surgery are anticipated to have a high clinical success rate for 6.2 ± 0.6 years. Plaque control and fracture morphology appeared to be significantly associated with the success of the multidisciplinary treatment approach.


Developmental Progression of the Coronary Vasculature in Human Embryos and Fetuses.
Although considerable advances in our understanding of mammalian and avian embryonic coronary development have occurred during the last decade, our current knowledge of this topic in humans is limited. Accordingly, the aim of this study was to determine if the development of the human coronary vasculature in humans is like that of other mammals and avians. The data document a progression of events involving mesenchymal cell-containing villi from the proepicardium, establishment of blood islands and a capillary network. The major finding of the study is direct evidence that the capillary plexus associated with spindle cells and erythroblasts invades the base of the aorta to form coronary ostia. A role for the dorsal mesocardium is also indicated by the finding that cells from this region are continuous with the aorta and pulmonary artery. The development of the tunica media of the coronary arteries follows the same base-apex progression as in other species, with the development of branches occurring late in the embryonic period. The fetal period is characterized by 1) growth and a numerical increase in the smallest arterial branches, veins, and venules, 2) innervation of arteries, and 3) inclusion of elastic fibers in the tunica media of the coronary arteries and development of the tunica adventitia. In conclusion, the data demonstrate that the development of the coronary system in humans is similar to that of other mammalian and avian species, and for the first time documents that the formation of the ostia and coronary stems in humans occurs by ingrowth of a vascular plexus and associated cells from the epicardium.


Qualitative and Quantitative Analyses of the Enantiomers of Nicotine and Nornicotine Employing Chiral Supercritical Fluid Chromatography.
An optimized method employing chiral supercritical fluid chromatography with diode array UV-VIS detection has been developed for the quantitative analysis of nicotine and nornicotine enantiomer distributions. The method parameters that were optimized included: column type (stationary phases, Chiralpak IG-3), column temperature (40°C), modifier types and concentration (isopropyl alcohol, 10%), additive types and concentrations (diethylamine, 0.2%), elution times (<6 min, flow rate 3 mL/min) and resolution factor (>1.2). These optimized conditions led to nicotine and nornicotine enantiomer detection limits of ~5 ng/μL with accompanying %RSD values of <2% from the analyses of commercially available nicotine-containing formulations.


Prevention of endometrial abnormalities.
Exogenous oestrogens are highly effective in relieving not only the acute symptoms of ovarian failure, such as vasomotor instability and vaginal dryness, but also in conserving postmenopausal bone mass. However, the oestrogen doses needed to achieve these benefits also induce endometrial proliferation. The risk of endometrial hyperplasia and carcinoma are thereby increased and unopposed oestrogen therapy is associated with a high incidence of abnormal vaginal bleeding requiring appropriate, invasive investigations. The cost-effectiveness of therapy and patient compliance are likely to be correspondingly reduced. Various strategies have been proposed to try to overcome the risk of endometrial hyperstimulation and these strategies have been reviewed. Based upon the available evidence, progestogen addition appears the most sensible and has been shown to be effective. It is now clear that progestogens should, in sequential therapies, be administered for 12 days each cycle for maximum protection. Concern has been expressed that the regular withdrawal bleed induced by sequential treatment will reduce patient compliance. Progestogens have, therefore, been added in a continuous fashion to try to prevent endometrial proliferation and thereby induce amenorrhoea. The ideal continuous, oestrogen/progestogen regimen has not yet been developed: all those evaluated to date are associated with a high incidence of breakthrough bleeding which is likely to restrict their use. Progestogens can cause undesirable physical, psychological and metabolic effects. The incidence and severity of side-effects will depend upon the type of progestogen prescribed, the route of administration, and the dose. Minimum effective daily doses of certain types of progestogens have now been established in terms of endometrial protection. Regrettably, few data are available on the physical and psychological effects of these progestogen doses: more information is available on lipid and lipoprotein effects but the data are confused and, at times, contradictory. More research is urgently needed to determine which of these progestogens is most suitable for addition to postmenopausal oestrogen therapy.


Feline immunodeficiency virus plasma load reduction by a retroinverso octapeptide reproducing the Trp-rich motif of the transmembrane glycoprotein.
The Trp-rich motif (TrpM) of the transmembrane glycoprotein (TM) of lentiviruses is an attractive domain on which to design new potential cell entry peptide inhibitors. We recently demonstrated that an octapeptide reproducing the TrpM of feline immunodeficiency virus (FIV), designated C8, broadly inhibited this virus in vitro and that the retroinverso analogue of this peptide (riC8) was almost as inhibitory and exhibited features suggestive of a much increased stability. Here, we demonstrated that riC8 is indeed highly stable, maintaining its concentration unchanged for at least 24 h in cat serum in vitro. Furthermore, once inoculated into cats, riC8 produced no major acute toxic effects and exhibited satisfactory pharmacokinetic properties. Finally, we report the results of a short-term monotherapy experiment in chronically FIV-infected cats showing that riC8 is well tolerated and also has substantial antiviral activity in vivo. In particular, the mean viral load of riC8-treated animals declined progressively with increasing time of treatment, whereas that of control animals given C8 or solvent alone did not. These results provide the first evidence that clinically useful inhibition of virus replication with a small peptide derived from a functional domain of the TM of a lentivirus can be achieved in vivo.


Effect of E-Beam Irradiation on Thermal and Mechanical Properties of Ester Elastomers Containing Multifunctional Alcohols.
The aim of this work was to investigate the thermal and mechanical properties of novel, electron beam-modified ester elastomers containing multifunctional alcohols. Polymers tested in this work consist of two blocks: sebacic acid-butylene glycol block and sebacic acid-sugar alcohol block. Different sugar alcohols were utilized in the polymer synthesis: glycerol, sorbitol, xylitol, erythritol, and mannitol. The polymers have undergone an irradiation procedure. The materials were irradiated with doses of 50 kGy, 100 kGy, and 150 kGy. The expected effect of using ionizing radiation was crosslinking process and improvement of the mechanical properties. Additionally, a beneficial side effect of the irradiation process is sterilization of the affected materials. It is also worth noting that the materials described in this paper do not require either sensitizers or cross-linking agent in order to perform radiation modification. Radiation-modified poly(polyol sebacate-co-butylene sebacate) elastomers have been characterized in respect to the mechanical properties (quasi-static tensile tests), cross-link density, thermal properties (Differential Scanning Calorimetry (DSC)), chemical properties: Fourier transform infrared spectroscopy (FTIR), and wettability (water contact angle). Poly(polyol sebacate-co-butylene sebacate) preopolymers were characterized with nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR) and gel permeation chromatography (GPC). Thermal stability of cross-linked materials (directly after synthesis process) was tested with thermogravimetric analysis (TGA).


Rural healthcare delivery and maternal and infant outcomes for diabetes in pregnancy: A systematic review.
The aim of this systematic review was to examine the literature regarding rural healthcare delivery for women with any type of diabetes in pregnancy, and subsequent maternal and infant outcomes. Eight databases were searched in September 2020, including Medline, EMCare, CINAHL, EMBASE, Maternity and Infant Care, Cochrane, Rural and Remote Health and Aboriginal and Torres Strait Islander Health bibliography. Studies from high-income countries in rural, regional or remote areas with interventions conducted during the antenatal period were included. Intervention details were reported using the template for intervention description and replication template. Two reviewers independently assessed for risk of bias using the RoB2 and ROBINS I tools. Three articles met the inclusion criteria: two conducted in Australia and one in the United States. A multidisciplinary approach was reported in two of the included studies, which were modified specifically for their respective rural settings. All three studies reported rates of caesarean section, birthweight (grams) and gestational age at birth as maternal and infant outcomes. One study was considered at moderate risk of bias, and two studies were at serious risk of bias. There is a significant gap in research relating to healthcare delivery for women with diabetes in pregnancy in rural areas. This lack of research is concerning given that 19% of individuals in high-income countries reside rurally. Further research is required to understand the implications of healthcare delivery models for diabetes in pregnancy in rural areas.


Abnormalities of presynaptic protein CDCrel-1 in striatum of rats reared in social isolation: relevance to neural connectivity in schizophrenia.
Post-weaning social isolation-rearing of rats leads to behavioural and neurochemical sequelae that model aspects of schizophrenia, and it may be useful to test hypotheses related to putative molecular mechanisms of the illness. In humans, the presynaptic protein CDCrel-1 represents an interesting candidate molecule for the mechanism and aetiology of schizophrenia. CDCrel-1 modulates dopamine neurotransmission, binds to the SNARE protein syntaxin and maps onto a region of chromosome 22q11 deleted in velo-cardio-facial and DiGeorge syndromes, which are associated with increased prevalence of schizophrenia. Using the isolation-rearing model, we measured immunoreactivity of the synaptic proteins CDCrel-1, synaptophysin and syntaxin. Male, Sprague-Dawley rats were raised in groups or in isolation for 12 weeks from weaning. Synaptic protein immunoreactivities were measured in striatal and hippocampal homogenates, using a sensitive enzyme-linked immunoadsorbent assay with monoclonal antibodies. Isolation-rearing produced region- and protein-specific effects. CDCrel-1 immunoreactivity was significantly lower in the striatum and marginally higher in the hippocampus of isolation-reared compared with socially reared animals. There were no statistically significant differences in synaptophysin immunoreactivity in either region. Confocal microscopy demonstrated a high degree of colocalization between the two presynaptic proteins. In striatum, a robust relationship between CDCrel-1 and syntaxin immunoreactivities was observed in socially reared rats, this was lost in the isolation-reared animals. Altered levels of the septin CDCrel-1 in isolation-reared rats may contribute to changes in neuronal connectivity and neurotransmission, and suggest a potential role for CDCrel-1 in schizophrenia related to chromosome 22q11 deletion syndrome.


[A case of coexisting borderline phyllodes tumor and non-invasive ductal carcinoma].
A 36-year-old woman with benign phyllodes tumor of the left breast had undergone lumpectomy 1 year ago and was admitted to our hospital because of a left breast mass on the operation scar. Ultrasonography showed a 35 mm low-echoic, elliptical mass with a high depth to width( D/W) ratio in the C area and a 10 mm low-echoic, polygonal mass with a high D/W ratio in the E area. Histological examination of an ultrasonography-guided vacuum-assisted biopsy specimen indicated recurrent phyllodes tumor. Since both tumors were assumed to be recurrent phyllodes tumors, quadrantectomy was performed. Finally, the mass in the C area was diagnosed as a recurrent phyllodes tumor and the mass in the E area was diagnosed as a fibroadenoma. A non-invasive ductal carcinoma was incidentally detected between the 2 tumors, and the surgical margin was negative. Radiotherapy was performed on the remnant breast tissue.


Circular Ribonucleic Acid circFTO Promotes Angiogenesis and Impairs Blood-Retinal Barrier Via Targeting the miR-128-3p/Thioredoxin Interacting Protein Axis in Diabetic Retinopathy.
Background: Increasing attention has been attracted by the role of circular RNAs (circRNAs) in ocular diseases. Previous study has revealed that circ_0005941 (also known as circFTO, an alpha-ketoglutarate-dependent dioxygenase) was upregulated in the vitreous humor of diabetic retinopathy (DR), while its underlying mechanism in DR remains unknown. Methods: Retinal vascular endothelial cells (RVECs) treated with high glucose (HG) were used to establish the DR cell model. The in vivo assays were conducted using streptozotocin-induced diabetic mice. The circular structure and stability of circFTO were identified by Sanger sequencing and RNase R treatment. RT-qPCR analysis was used to detect the RNA expression. The levels of the mRNA-encoded protein thioredoxin-interacting protein (TXNIP) or angiogenesis-associated proteins (VEGFA, PDGF, and ANG2) and blood-retinal barrier (BRB)-related proteins (ZO-1, Occludin, and Claudin-5) were measured by Western blot. The viability of RVECs was measured using CCK-8 assays. The angiogenesis of RVECs was assessed using tube formation assays in vitro. Endothelial permeability assays were conducted to examine the function of the BRB. The binding between genes was explored using RNA pulldown and luciferase reporter assays. Results: CircFTO was upregulated in HG-treated RVECs. CircFTO deficiency reversed the HG-induced increase in the viability and angiogenesis of RVECs and alleviated HG-mediated impairment of the BRB. MiR-128-3p bound with circFTO and was downregulated in HG-treated RVECs. TXNIP was a downstream target gene of miR-128-3p. TXNIP was highly expressed in the DR cell model. Rescue assays revealed that circFTO promoted angiogenesis and impaired the blood-retinal barrier by upregulating TXNIP. In the DR mouse model, circFTO silencing inhibited angiogenesis and promoted BRB recovery in vivo. Conclusion: CircFTO promotes angiogenesis and impairs the blood-retinal barrier in vitro and in vivo by binding with miR-128-3p to upregulate TXNIP in DR.


Lack of correlation of plasma norepinephrine and dopamine-beta-hydroxylase in hypertensive and normotensive subjects.
Dopamine-beta-hydroxylase (DBH) and norepinephrine (NE) have been determined in over 350 plasma samples from 174 subjects while resting supine (basal sample), standing, or exercising. Although increments in both NE and DBH were found with postural change, the further increase in plasma levels of NE during exertion was not attended by any change in levels of DBH. There was no significant correlation between basal levels of DBH and NE nor was there any correlation in their increments after standing or exercising. DBH activity in plasma of subjects with moderate essential hypertension was not different from that of normotensive subjects. It is concluded that plasma DBH is a poor index of acute sympathetic neuronal activity.


Discriminating Self and Non-Self by RNA: Roles for RNA Structure, Misfolding, and Modification in Regulating the Innate Immune Sensor PKR.
Pathogens are recognized by the innate immune system in part via their unique and complex RNA signatures. A key sensor in human innate immunity is the RNA-activated protein kinase, protein kinase R (PKR), which has two double-stranded RNA (dsRNA) binding motifs (dsRBMs) at its N-terminus. Early studies described PKR as being activated potently by long stretches of perfect dsRNA, a signature typical of viruses. More recently, we and others have found that PKR is also activated by RNAs having structural defects such as bulges and internal loops. This Account describes advances in our understanding of the ability of PKR to detect diverse foreign RNAs and how that recognition plays significant roles in discriminating self from non-self. The experiments discussed employ a wide range of techniques including activation assays, native polyacrylamide gel electrophoresis (PAGE), protein footprinting, and small-angle X-ray scattering (SAXS). We discuss how misfolding and dimerization of RNA lead to activation of PKR. We also present recent findings on the activation of PKR by varied bacterial functional RNAs including ribozymes and riboswitches, which are among the few structured RNAs known to interact with PKR in a site-specific manner. Molecular models for how these structured RNAs activate PKR are provided. Studies by SAXS revealed that PKR straightens bent RNAs. Most external and internal RNA cellular modifications introduced in vitro and found naturally, such as the m7G cap and m6A group, abrogate activation of PKR, but other modifications, such as 5'-ppp and 2'-fluoro groups, are immunostimulatory and potential anticancer agents. Genome-wide studies of RNA folding in vitro and in vivo have provided fresh insights into general differences in RNA structure among bacteria, viruses, and human. These studies suggest that in vivo, cellular human RNAs are less folded than once thought, unwound by helicases, destabilized by m6A modifications, and often bound up with proteins, all conditions known to abrogate activation of PKR. It thus appears that non-self RNAs are detected as unmodified, naked RNAs with appreciable secondary and tertiary structure. Observation that PKR is activated by structured but otherwise diverse RNAs is consistent both with the broad-spectrum nature of innate immunity and the nonspecific recognition of RNA by the dsRBM family. These findings provide a possible explanation for the apparent absence of protein-free structured human RNAs, such as ribozymes and riboswitches.


Living donor liver transplantation for biliary atresia complicated by situs inversus: technical highlights.
Living-donor liver transplantation (LDLT) has become an established technique to treat children with end-stage liver disease. Biliary atresia (BA), one of the most common indications for liver transplantation in children, can be associated with situs inversus (SI). In the past, the presence of SI has been considered to be an absolute contraindication for liver transplantation because of the technical difficulties. Recently, some reports of successful diseased-donor liver transplantation in patients with BA complicated by SI have been published; however, few reports of that with LDLT exist. The technical difficulties involved with LDLT for such cases have not been described. Herein, we present 4 successful cases of LDLT for BA with SI. Complex anomalies associated with SI, such as a hepatic artery arising from the supraceliac aorta, a preduodenal portal vein, and absence of the retrohepatic inferior vena cava, increase the technical difficulties involved with the operation. Additional caution is required in LDLT because a living-donor graft has short vessels and the availability of vascular grafts from the donor is limited. In conclusion, LDLT for BA complicated by SI can be managed successfully with technical modifications and scrupulous attention. This series represents the largest reported group of patients with BA complicated by SI who underwent a successful LDLT procedure.


Mapping interdisciplinary fields: efficiencies, gaps and redundancies in HIV/AIDS research.
While interdisciplinarity continues to increase in popularity among funders and other scientific organizations, its potential to promote scientific advances remains under-examined. For HIV/AIDS research, we examine the dynamics of disciplinary integration (or lack thereof) providing insight into a field's knowledge base and those questions that remain unresolved. Drawing on the complete histories of two interdisciplinary journals, we construct bibliographic coupling networks based on overlapping citations to identify segregation into research clusters and estimate topic models of research content. We then compare how readily those bibliographic coupling clusters account for the structuring of topics covered within the field as it evolves over two decades. These comparisons challenge one-dimensional and/or cross-sectional approaches to interdisciplinarity. Some topics are increasingly coordinated across disciplinary boundaries (e.g., vaccine development); others remain relatively segmented into disconnected disciplinary domains for the full period (e.g., drug resistance). This divergence indicates heterogeneity in interdisciplinarity and emphasizes the need for critical approaches to studying the organization of science.


Methylphenidate: pulmonary hypertension and heart valve disease.
Several amphetamine-like appetite suppressants are known to have cardiovascular adverse effects, in particular pulmonary arterial hypertension and cardiac valve disease. Is this also the case with methylphenidate, an amphetamine-like psychostimulant used in attention-deficit hyperactivity disorder (especially in children) and also in narcolepsy? Cases of pulmonary hypertension and heart valve disease have been reported with methylphenidate, including in children. The risk appears to be low, but epidemiological studies are needed to estimate the incidence. This risk should be minimised by only using methylphenidate to treat serious disorders, at the lowest effective dose. Attention should be paid to warning signs such as dyspnoea.


First-in-human trial of a novel suprachoroidal retinal prosthesis.
Retinal visual prostheses ("bionic eyes") have the potential to restore vision to blind or profoundly vision-impaired patients. The medical bionic technology used to design, manufacture and implant such prostheses is still in its relative infancy, with various technologies and surgical approaches being evaluated. We hypothesised that a suprachoroidal implant location (between the sclera and choroid of the eye) would provide significant surgical and safety benefits for patients, allowing them to maintain preoperative residual vision as well as gaining prosthetic vision input from the device. This report details the first-in-human Phase 1 trial to investigate the use of retinal implants in the suprachoroidal space in three human subjects with end-stage retinitis pigmentosa. The success of the suprachoroidal surgical approach and its associated safety benefits, coupled with twelve-month post-operative efficacy data, holds promise for the field of vision restoration. Clinicaltrials.gov NCT01603576.


Current understanding of the mechanisms of idiosyncratic drug-induced agranulocytosis.
Idiosyncratic drug-induced agranulocytosis (IDIAG) is a life-threatening adverse reaction characterized by an absolute neutrophil count < 500 cells/μl of blood. It shares many of the characteristics of other idiosyncratic drug reactions (IDRs), and this presumably reflects mechanistic similarities. This review describes the evidence for mechanistic hypotheses of IDIAG and new hypotheses are explored. The characteristics of IDIAG are most consistent with an immune mechanism. Where genetic studies have been done, the genes associated with an increased risk of IDIAG are either human leukocyte antigen genes or other genes associated with the immune response, which provides further evidence for an immune mechanism. There is evidence that the immune response leading to most IDRs is triggered by reactive metabolites of the offending drug, and most drugs that are associated with IDIAG are either known to be oxidized to a reactive metabolite by neutrophils or have a functional group that has the potential to be easily oxidized to a reactive metabolite. There is new evidence that drugs that cause IDRs including IDIAG can activate inflammasomes. Thus, the ability of a drug to be oxidized to a reactive metabolite by neutrophils and to activate inflammasomes may be useful biomarkers to predict IDIAG risk.


[Secretion into the circulating medium of lipids synthetized by isolated Wistar rat liver perfused with high concentrations of oleic acid and glycerol].
In previously 18-h fasting Wistar rats, the liver is isolated and perfused with [9, 10(-3)H2] oleic acid (346 mumol and [1-14C] glycerol (115 mumol). Then, in a circulating medium, the secretion of triacylglycerols -- synthetized de novo and by esterification of exogenous oleic acid -- and VLDL is inhibited. On the other hand, the secretion of phospholipids is getting away that regulatory process.


Hypoxia enhances the stemness markers of cochlear stem/progenitor cells and expands sphere formation through activation of hypoxia-inducible factor-1 alpha.
Unlike neural stem cells that maintain populations in the adult brains of both rodents and humans, cochlear stem cells appear to diminish in number after birth and may become quiescent in adult mammalian cochleae. Hypoxia has been observed to promote an undifferentiated cell state in various stem cell populations; however, little is known about such an effect on cochlear stem/progenitor cells (SPCs). The aims of this study were to assess the effect of hypoxia on cochlear SPCs and to examine the impact of hypoxia-inducible factor-1 alpha (Hif-1a) on regulating such an effect. Our data demonstrate that hypoxic culturing for 24 h significantly increased sphere formation and viability of cochlear SPCs compared with those cultured under normoxic conditions. Concurrent with these proliferation promotion effects are changes in the expression of multiple stemness and cell-cycle quiescent associated gene targets, including Abcg2, nestin, p27(Kip1)and Vegf. Knockdown of Hif-1a expression by small-interfering RNA inhibited hypoxia-induced cochlear SPC expansion and resulted in downregulation of Vegf, Abcg2, and nestin and upregulation of p27(Kip1) gene expression. These results suggest that Hif-1a plays an important role in the stimulation of the proliferation of cochlear SPCs, which confers a great benefit of expanding cochlear SPCs via hypoxic conditions.


Natural rubber latex and chestnut allergy: cross-reactivity or co-sensitization?
Chestnut and natural rubber latex (NRL) allergy are often associated in the latex-fruit syndrome. To establish whether the concurrent NRL and chestnut IgE antibody reactivity are the results of co-sensitization or cross-reactivity. Sera from 19 patients with chestnut- and NRL-specific IgE were selected and tested for reactivity with recombinant (r) latex allergens. Cross-reactivity was explored by IgE-inhibition experiments using chestnut or NRL allergens as solid phase on ImmunoCAP. IgE-antibodies were detected to rHev b 6.01 (prohevein) in 58% of the sera, to rHev b 5 in 32%, to rHev b 12 in four of 13 sera, to rHev b 7.02 and rHev b 11 in four, and to rHev b 1 in two of 19 sera. rHev b 8-IgE antibodies were found in nine sera (47%), whereas six displayed mono-sensitization to rHev b 8 with regard to our test panel. Three of 16 sera showed IgE to cross-reactive carbohydrate determinants. In most sera recognizing rHev b 5 and/or rHev b 6.01 as major allergens the IgE-reactivity to NRL remained unaffected by chestnut extract and chestnut-IgE remained unaffected by NRL extract. Conversely, in sera with rHev b 8 as dominant allergen IgE-binding to NRL was nearly completely inhibited by chestnut and vice versa. IgE-binding to rHev b 8 was abolished by chestnut extract. Although patients have concomitant IgE antibody reactivity to chestnut and NRL, cross-reactivity could be demonstrated mainly in those patients with IgE to Hev b 8 (profilin) from NRL.


Delamanid for multidrug-resistant pulmonary tuberculosis.
Delamanid (OPC-67683), a nitro-dihydro-imidazooxazole derivative, is a new antituberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis. In this randomized, placebo-controlled, multinational clinical trial, we assigned 481 patients (nearly all of whom were negative for the human immunodeficiency virus) with pulmonary multidrug-resistant tuberculosis to receive delamanid, at a dose of 100 mg twice daily (161 patients) or 200 mg twice daily (160 patients), or placebo (160 patients) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines. Sputum cultures were assessed weekly with the use of both liquid broth and solid medium; sputum-culture conversion was defined as a series of five or more consecutive cultures that were negative for growth of M. tuberculosis. The primary efficacy end point was the proportion of patients with sputum-culture conversion in liquid broth medium at 2 months. Among patients who received a background drug regimen plus 100 mg of delamanid twice daily, 45.4% had sputum-culture conversion in liquid broth at 2 months, as compared with 29.6% of patients who received a background drug regimen plus placebo (P=0.008). Likewise, as compared with the placebo group, the group that received the background drug regimen plus 200 mg of delamanid twice daily had a higher proportion of patients with sputum-culture conversion (41.9%, P=0.04). The findings were similar with assessment of sputum-culture conversion in solid medium. Most adverse events were mild to moderate in severity and were evenly distributed across groups. Although no clinical events due to QT prolongation on electrocardiography were observed, QT prolongation was reported significantly more frequently in the groups that received delamanid. Delamanid was associated with an increase in sputum-culture conversion at 2 months among patients with multidrug-resistant tuberculosis. This finding suggests that delamanid could enhance treatment options for multidrug-resistant tuberculosis. (Funded by Otsuka Pharmaceutical Development and Commercialization; ClinicalTrials.gov number, NCT00685360.).


Feto-placental Dopplers are not altered in women with obstructive sleep apnoea symptoms.
Snoring, gasping or choking during sleep are common symptoms of sleep-disordered breathing and are associated with multiple adverse maternal and obstetric outcomes. The mechanisms responsible remain unknown; however, placental dysfunction is suspected. The aim of this study was to investigate feto-placental and fetal cardiac function in women with pregnancies complicated by obstructive sleep apnoea symptoms. This was a prospective observational cohort study at a large tertiary obstetric hospital in Australia. Women were asked to complete a questionnaire relating to the presence and severity of obstructive sleep apnoea symptoms. They also underwent an ultrasound scan where Doppler indices of various feto-placental vessels and fetal cardiac function were measured. Regional cerebral perfusion was also assessed. A total of 255 women were included in the final analysis. Of these, 36.1% (92/255) of women reported no obstructive sleep apnoea symptoms; 63.9% (163/255) reported they experienced some form of obstructive sleep apnoea symptoms that included any frequency of snoring or choking/gasping, while 42.0% (107/255) complained of severe obstructive sleep apnoea symptoms (snoring ≥ 3 times a week or choking/gasping). There were no significant differences in feto-placental Dopplers or fetal cardiac function parameters in women with obstructive sleep apnoea symptoms. There were also no differences in regional cerebral blood flow between groups, or any correlation with severity of symptoms. Our data challenge the current perspective that adverse perinatal outcomes in women with obstructive sleep apnoea symptoms are related primarily to placental dysfunction and fetal compromise.


Boxfish swimming paradox resolved: forces by the flow of water around the body promote manoeuvrability.
The shape of the carapace protecting the body of boxfishes has been attributed an important hydrodynamic role in drag reduction and in providing automatic, flow-direction realignment and is therefore used in bioinspired design of cars. However, tight swimming-course stabilization is paradoxical given the frequent, high-performance manoeuvring that boxfishes display in their spatially complex, coral reef territories. Here, by performing flow-tank measurements of hydrodynamic drag and yaw moments together with computational fluid dynamics simulations, we reverse several assumptions about the hydrodynamic role of the boxfish carapace. Firstly, despite serving as a model system in aerodynamic design, drag-reduction performance was relatively low compared with more generalized fish morphologies. Secondly, the current theory of course stabilization owing to flow over the boxfish carapace was rejected, as destabilizing moments were found consistently. This solves the boxfish swimming paradox: destabilizing moments enhance manoeuvrability, which is in accordance with the ecological demands for efficient turning and tilting.


Effect of multiple peritumoral regions of interest ranges based on computed tomography radiomics for the prediction of early recurrence of hepatocellular carcinoma after resection.
Early recurrence (ER) of hepatocellular carcinoma (HCC) is defined as recurrence that occurs within two years after resection. Our study aimed to determine the optimal peritumoral regions of interest (ROI) range by comparing the effect of multiple peritumoral radiomics ROIs on predicting ER of HCC, and to develop and validate a combined clinical-radiomics prediction model. A total of 160 HCC patients were randomly divided into a training cohort (n=112) and a validation cohort (n=48). The intratumoral original ROI was outlined based on enhanced computed tomography images and then used as the base to sequentially extend outward 1-5 mm to form peritumoral ROI. We developed a logistic regression model to predict ER of HCC. The efficacy of different ROI prediction models was compared to determine the optimal ROI. The combined model divided the patients into a high-risk group and low-risk group. Ninety-seven (60.6%) of the patients were ER; the remaining 63 (39.4%) were not ER. The area under the curve values and 95% confidence intervals for ROI 3 were 0.867 (0.802-0.933) and 0.807 (0.682-0.931) in the training and validation cohorts, respectively, and ROI 3 was identified as the optimal ROI. Multivariate logistic regression analysis determined microvascular invasion (MVI) (P=0.037) and alpha-fetoprotein (AFP) (P=0.013) to be independent risk factors for ER. The combined clinical-radiomic model containing the radiomics score, MVI, and AFP had the optimal predictive efficacy, with area under the curve values and 95% confidence intervals of 0.903 (0.848-0.957) and 0.830 (0.709-0.952) in the training and validation cohort, respectively. Subgroup analysis showed significantly ER predicted in the high-risk group than the low-risk group (P<0.001). Peritumoral radiomics 3 mm range was determined as the optimal ROI in this study. The clinical-radiomics combined models can effectively stratify high- and low-risk patients for timely clinical treatment and decision making.


Immediate reconstruction of the central segment of the mandible using the masseter osteomuscular flap.
We describe a new technique for reconstruction of the central segment of the mandible using a masseter osteomuscular flap. The advantages of this method are that bone viability is preserved, both form and function of the mandible are maintained, it is a local flap with low donor-site morbidity, and the operative time is shortened.


Synthesis and biological evaluation of pentacyclic strychnos alkaloids as selective modulators of the ABCC10 (MRP7) efflux pump.
The selective modulation of ATP-binding cassette (ABC) efflux pumps overexpressed in multidrug resistant cancers (MDR) and attendant resensitization to chemotherapeutic agents represent a promising strategy for treating cancer. We have synthesized four novel pentacyclic Strychnos alkaloids alstolucines B (2), F (3), and A (5) and N-demethylalstogucine (4), in addition to known Strychnos alkaloid echitamidine (16), and we evaluated compounds 1-5 in biochemical assays with ABCC10 and P-glycoprotein (P-gp). Alstolucines B (2) and F (3) inhibited ABCC10 ATPase activity at 12.5 μM without affecting P-gp function; moreover, they resensitized ABCC10-transfected cell lines to paclitaxel at 10 μM. Altogether, the alstolucines represent promising lead candidates in the development of modulators of ABCC10 for MDR cancers overexpressing this pump.


The first, holistic immunological model of COVID-19: Implications for prevention, diagnosis, and public health measures.
The natural history of COVID-19 caused by SARS-CoV-2 is extremely variable, ranging from asymptomatic or mild infection, mainly in children, to multi-organ failure, eventually fatal, mainly in the eldest. We propose here the first model explaining how the outcome of first, crucial 10-15 days after infection, depends on the balance between the cumulative dose of viral exposure and the efficacy of the local innate immune response (natural IgA and IgM antibodies, mannose-binding lectin). If SARS-CoV-2 runs the blockade of this innate immunity and spreads from the upper airways to the alveoli in the early phases of the infections, it can replicate with no local resistance, causing pneumonia and releasing high amounts of antigens. The delayed and strong adaptive immune response (high-affinity IgM and IgG antibodies) that follows, causes severe inflammation and triggers mediator cascades (complement, coagulation, and cytokine storm), leading to complications often requiring intensive therapy and being, in some patients, fatal. Low-moderate physical activity can still be recommended. However, extreme physical activity and oral breathing with hyperventilation during the incubation days and early stages of COVID-19 facilitates re-inhalation and early direct penetration of high numbers of own virus particles in the lower airways and the alveoli, without impacting on the airway's mucosae covered by neutralizing antibodies ("viral auto-inhalation" phenomenon). This allows the virus to bypass the efficient immune barrier of the upper airway mucosa in already infected, young, and otherwise healthy athletes. In conclusion, whether the virus or the adaptive immune response reaches the lungs first is a crucial factor deciding the fate of the patient. This "quantitative and time-/sequence-dependent" model has several implications for prevention, diagnosis, and therapy of COVID-19 at all ages.


Preventive Health Care for Women Who Have Sex with Women.
Despite recent shifts in societal attitudes toward same-sex relationships, women who have sex with women face a variety of barriers to optimal health, including a history of negatively perceived interactions in clinical settings that lead them to delay or avoid health care. Women who have sex with women may be at disproportionate risk of obesity, tobacco use, substance use, mental health issues, intimate partner violence, sexually transmitted infections, and some cancers. Disparities can exist throughout the lifetime. Lesbian and bisexual adolescents are vulnerable to bullying, family rejection, and risky sexual behavior that may lead to sexually transmitted infections or unintended pregnancy. Sexual minority stress, which is a response to stigmatization, prejudice, and internalized homophobia, contributes to many of these conditions. Family physicians should foster trust and communication to provide a nonjudgmental, welcoming environment supportive of culturally competent health care and optimal outcomes. When indicated, clinicians should refer women who have sex with women to culturally sensitive community resources and legal advisors for assistance with medical decision making, hospital visitation, conception, and legal recognition of nonbiologic parents.


Comparison of the Clinical Implications among Five Different Nutritional Indices in Patients with Lupus Nephritis.
Systemic lupus erythematosus (SLE) is characterized with aberrant responses in the immune systems and lupus nephritis (LN) is one of the most serious complications of SLE. This study evaluated the clinical significance of different nutritional indices in 207 renal biopsy-proven LN patients. The clinical and laboratory data were reviewed, and five different nutritional indices were calculated: (i) Controlling nutritional status (CONUT) score; (ii) prognostic nutritional index (PNI); (iii) nutritional risk index; (iv) neutrophil-to-lymphocyte ratio; and (v) body mass index. The factors associated with end-stage renal failure (ESRF) were assessed using a Cox-proportional hazard analysis. The patients with ESRF had significantly lower median PNI (31.1 vs. 34.7, p = 0.012) than those without ESRF at baseline. The CONUT score and PNI had the highest correlation between the SLE disease activity index-2000 (r = 0.467 and p = -0.356, all p < 0.001) and was significantly associated with SLE activity-related measures. In the Cox-proportional hazard analysis, PNI (odds ratio 0.925, 95% confidence interval 0.865-0.989, p = 0.022) was independently associated with ESRF along with creatinine and chronicity index, and the renal survival rate was significantly lower in patients with PNI ≤35.41 than in those with PNI >35.41 (p = 0.003). Among nutritional indices, the CONUT score and PNI better correlated with disease activity and PNI was associated with ESRF.


Hyaline bodies of odontogenic cysts: histological, histochemical and electron microscopic studies.
Hyaline bodies of odontogenic cyst were examined by histological, histochemical and electron microscopic observations. They were seen only in odontogenic cysts and their prevalence was 6.9% in 576 cases of the cysts. They occurred most frequently within the epithelial lining, but a few bodies were observed in the connective tissue walls. Histochemical reactions of hyaline bodies were similar to those of dental cuticles, but differed from keratin. Ultrastructurally, hyaline bodies were typed into two forms: lamellated and homogeneous. The lamellated bodies were composed of alternate electron-dense and electron-lucent layers. The homogeneous bodies were occasionally formed around granular material, mineralized masses and cholesterol clefts. Hyaline bodies adjoined epithelial cells via a basal lamina-like structure and half-desmosomes. Epithelial cells containing well-developed, rough surfaced, endoplasmic reticulum were seen adjacent to hyaline bodies. Ferritin-like granules were found in the cytoplasm of epithelial cells near hyaline bodies. By electron probe X-ray microanalysis, inorganic elements within the ferritin-like granules were the same in constitution as those in the outermost electron-dense layer of the lamellated bodies. By scanning electron microscopy, hyaline bodies displayed ellipsoidal and stick-like shapes. The present study suggested that hyaline bodies are particular products formed by odontogenic epithelium.


Differentiated selves can surely be good for the group, but let's get clear about why.
We applaud the goal of reconciling the self and group literatures and agree that a differentiated self may sometimes improve group outcomes. Nevertheless, greater precision regarding the underlying mechanisms is needed. Specifically, differentiated selves improve outcomes by overriding selfishness when they allow for personal regulation (being personally recognized and valued) rather than social regulation (specialization of labor).


The Role of Triglyceride-rich Lipoproteins and Their Remnants in Atherosclerotic Cardiovascular Disease.
Atherosclerotic cardiovascular disease (ASCVD) is the world's leading cause of death. ASCVD has multiple mediators that therapeutic interventions target, such as dyslipidaemia, hypertension, diabetes and heightened systemic inflammatory tone, among others. LDL cholesterol is one of the most well-studied and established mediators targeted for primary and secondary prevention of ASCVD. However, despite the strength of evidence supporting LDL cholesterol reduction by multiple management strategies, ASCVD events can still recur, even in patients whose LDL cholesterol has been very aggressively reduced. Hypertriglyceridaemia and elevated levels of triglyceride-rich lipoproteins (TRLs) may be key contributors to ASCVD residual risk. Several observational and genetic epidemiological studies have highlighted the causal role of triglycerides within the TRLs and/or their remnant cholesterol in the development and progression of ASCVD. TRLs consist of intestinally derived chylomicrons and hepatically synthesised very LDL. Lifestyle modification has been considered the first line intervention for managing hypertriglyceridaemia. Multiple novel targeted therapies are in development, and have shown efficacy in the preclinical and clinical phases of study in managing hypertriglyceridaemia and elevated TRLs. This comprehensive review provides an overview of the biology, pathogenicity, epidemiology, and genetics of triglycerides and TRLs, and how they impact the risk for ASCVD. In addition, we provide a summary of currently available and novel emerging triglyceride-lowering therapies in development.


Comparison of personality traits, attitude toward orthodontic treatment, and pain perception and experience before and after orthodontic treatment.
To compare personality traits, attitude toward orthodontic treatment, and pain perception and experience before and after orthodontic treatment. One hundred subjects (50 male and 50 female) were included in this study. The mean (SD) age was 17.5 (2.05) years at T1 and 19.15 (2.32) years at T2. The instruments for data collection were questionnaires that included assessment of patients' personality traits, attitudes toward orthodontic treatment, and pain perception/experience. Subjects completed the questionnaires at two different times: before orthodontic treatment (T1) and after fixed orthodontic treatment (T2). Subjects were treated by fixed orthodontic appliances for an average (SD) period of 18.64 (0.35) months. Paired sample t-test and chi-square test were used to detect any differences. Significant changes in personality traits were detected after orthodontic treatment irrespective of gender. Neuroticism, openness, agreeableness, and conscientiousness scores were improved (P < .001). A positive attitude toward orthodontic treatment was reported at T1 (4.31 [±1.26]) and improved at T2 (3.98 [±1.16]) irrespective of gender (P < .05). The average (SD) expected pain score (T1) was 4.73 (1.88) and the average (SD) experienced pain score (T2) was 4.63 (1.58). Significant difference in the expected and experienced pain scores was not detected (P = .11). Personality traits and attitude toward orthodontic treatment improved after orthodontic treatment. Reported actual pain experience during orthodontic treatment was similar to that expected before treatment.


Thrombopoietin-responsive essential thrombocythaemia with myelofibrosis.
Platelet-derived growth factor (PDGF) and other cytokines released from megakaryocytes are thought to play a crucial role in the pathogenesis of myelofibrosis. We describe a patient with essential thrombocythaemia (ET) who developed myelofibrosis with an increased level of serum thrombopoietin (TPO). Recombinant human (rh) TPO stimulated the proliferation and spontaneous megakaryocyte colony formation of the neoplastic cells in the peripheral blood. Moreover, serum concentrations of PDGF, platelet factor 4, and beta-thromboglobulin were elevated and the production of these growth factors from the megakaryocyte progenitors was augmented with the addition of rhTPO in vitro. These results indicate that TPO may contribute to the development of myelofibrosis in ET.


In vitro antioxidant capacities of eight different kinds of apples and their effects on lipopolysaccharide-induced oxidative damage in mice.
In the present study, the DPPH and ABTS+ radical scavenging activity of eight types of apples decreased (P < 0.05) during the 70-day storage at 4°C. The Fushi (F2) apples from Xin Jiang showed the highest radical scavenging activity. For in vivo study, 40 male Kunming mice (body weight 20-25 g) were selected and randomly assigned to four groups (10 mice per group). The F2 groups (F2S, F2 + sterile saline and F2L, F2 + lipopolysaccharide) were administered with 0.3 mL F2 filtrate via gastric intubation daily for 28 days. The control groups (CS, CON + sterile saline and CL, CON + lipopolysaccharide) were treated with sterile saline at the same volume. At day 29, mice of F2L and CL groups were injected with 100 μg/kg body weight of lipopolysaccharide (LPS) intraperitoneally, while those of F2S and CS groups were injected equal volume of sterile saline. In comparison to the CS group, the CL group showed a decrease (P < 0.05) in serum, liver, and hepatic mitochondrial antioxidant capacity, reduction (P < 0.05) in the expression of hepatic antioxidant-related genes, and an increase (P < 0.05) in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), protein carbonyl (PC), and reactive oxygen species (ROS). In comparison to the CL group, the F2L group showed lower (P < 0.05) levels of serum ALT, AST, and ROS, higher (P < 0.05) level of serum, liver, and hepatic mitochondrial antioxidant capacity, increased mitochondrial membrane potential (MMP), and enhanced (P < 0.05) expression of hepatic antioxidant-related genes. These results suggest that F2 may exert protective effect against LPS-induced oxidative damage by improving the antioxidant capacity.


A rare case of successful percutaneous drainage of a methicillin-resistant Staphylococcus aureus prostatic abscess extending into the penis and revealing diabetes mellitus.
In the postantibiotic era, prostatic abscesses (PAs) are rare, affecting primarily immunocompromised men and/or caused by atypical drug-resistant pathogens, raising both diagnostic and management challenges. PA caused by methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon condition and also a primary source of bacteremia. Nevertheless, the continued pattern of increase in reported cases, due especially to community-associated strains, is a growing concern regarding the significant morbidity and mortality. Besides proper antibiotics, drainage of a PA may be required, which is usually transrectal or transurethral. Herein, we describe the case of MRSA PA extending into the penis with concomitant MRSA bacteremia of unknown origin, whereupon diabetes mellitus was newly diagnosed in a previously healthy man residing in a community setting, and managed successfully by a transperineal drainage with good outcome. This case also highlights that individuals diagnosed with such rare deep-seated MRSA infections should be assessed for undiagnosed comorbidities. To the best of our knowledge, this is the first reported case of percutaneous drainage of a PA by using a double-lumen catheter.


Tissue Sodium Concentration within White Matter Correlates with the Extent of Small Vessel Disease.
Sodium MRI (23Na MRI) derived biomarkers such as tissue sodium concentration (TSC) provide valuable information on cell function and brain tissue viability and has become a reliable tool for the assessment of brain tumors and ischemic stroke beyond pathoanatomical morphology. Patients with major stroke often suffer from different degrees of underlying white matter lesions (WMLs) attributed to chronic small vessel disease. This study aimed to evaluate the WM TSC in patients with an acute ischemic stroke and to correlate the TSC with the extent of small vessel disease. Furthermore, the reliability of relative TSC (rTSC) compared to absolute TSC in these patients was analyzed. We prospectively examined 62 patients with acute ischemic stroke (73 ± 13 years) between November 2016 and August 2019 from which 18 patients were excluded and thus 44 patients were evaluated. A 3D 23Na MRI was acquired in addition to a T2-TIRM and a diffusion-weighted image. Coregistration and segmentation were performed with SPM 12 based on the T2-TIRM image. The extension of WM T2 hyperintense lesions in each patient was classified using the Fazekas scale of WMLs. The absolute TSC in the WM region was correlated to the Fazekas grades. The stroke region was manually segmented on the coregistered absolute diffusion coefficient image and absolute, and rTSC was calculated in the stroke region and compared to nonischemic WM region. Statistical significance was evaluated using the Student t-test. For patients with Fazekas grade I (n = 25, age: 68.5 ± 15.1 years), mean TSC in WM was 55.57 ± 7.43 mM, and it was not statistically significant different from patients with Fazekas grade II (n = 7, age: 77.9 ± 6.4 years) with a mean TSC in WM of 53.9 ± 6.4 mM, p = 0.58. For patients with Fazekas grade III (n = 9, age: 81.4 ± 7.9 years), mean TSC in WM was 68.7 ± 10.5 mM, which is statistically significantly higher than the TSC in patients with Fazekas grade I and II (p < 0.001 and p = 0.05, respectively). There was a positive correlation between the TSC in WM and the Fazekas grade with r = 0.48 p < 0.001. The rTSC in the stroke region was statistically significant difference between low (0 and I) and high (2 and 3) Fazekas grades (p = 0.0353) whereas there was no statistically significant difference in absolute TSC in the stroke region between low (0 and I) and high (2 and 3) Fazekas grades. The significant difference in absolute TSC in WM in patients with severe small vessel disease; Fazekas grade 3 can lead to inaccuracies using rTSC quantification for evaluation of acute ischemic stroke using 23 Na MRI. The study, therefore, emphasizes the importance of absolute tissue sodium quantification.


[An unusual presentation of painful tic convulsive].
The term 'painful tic convulsive' is used to describe the syndrome involving concomitant hemifacial spasm and ipsilateral trigeminal neuralgia. Vascular compression of the fifth and seventh cranial nerves is the most common cause, involving the entry and exit zone of rootlets coming from the brainstem; nevertheless, different etiologies of this syndrome has been previously reported. Treatment for this disease is based on surgical microvascular decompression of the nerve rootlets, but still a topic of debate. A 63-year-old woman with history of 14 years presenting left trigeminal neuralgia, associated with ipsilateral hemifacial spasm for more than ten years. Medical treatment was installed without adequate symptom control. Patient was subjected to surgical treatment via a microasterional approach, with dissection of arachnoid fibrous tissue surrounding fifth and seventh nerves during the first surgery. A second surgery was performed with insertion of a teflon fragment aside of each exit nerve root (V and VII-VIII complex). Symptoms resolved immediately after the surgery and has persisted during the 1-year follow-up. Painful tic convulsive etiology could be multifactorial. This report is the first clinical case describing basal arachnoiditis as a primary cause of painful tic convulsive.


Supplemental alanylglutamine, organ growth, and nitrogen metabolism in neonatal pigs fed by total parenteral nutrition.
The objective of this study was to determine whether supplemental glutamine (alanylglutamine dipeptide) is effective in preventing small intestinal mucosal atrophy associated with total parenteral nutrition and whether it affects the growth of other organs in neonatal pigs. We compared organ growth, intestinal enzyme activity, and plasma nitrogen metabolites in 4-day-old pigs randomly selected to receive total parenteral nutrition supplemented with 0 g, 2.0 g, or 4.5 g of glutamine per deciliter for a total amino acid intake of either 11 or 25 g.kg-1.d-1 for 7 days. Glutamine supplementation increased (60% to 100%) plasma concentrations of glutamine, urea nitrogen, ammonia, and both jejunal villus height and surface area, but it did not significantly affect jejunal mucosal protein and DNA masses or the relative growth of liver, kidneys, and brain. No histologic evidence of tissue toxicity was found. Supplementing large amounts of glutamine (alanylglutamine dipeptide) did not completely prevent total parenteral nutrition-associated intestinal mucosal atrophy but did improve villus morphology without affecting vital organ growth or histology.


Marginal bone preservation in single-tooth replacement: a 5-year prospective clinical multicenter study.
Few long-term studies are available comparing immediate and conventional loading protocols of implant-supported single-tooth replacement. The aim of the present randomized controlled clinical trial was to evaluate prospectively the 5-year clinical and radiological outcome of immediate functional loading implants used in single-tooth replacement. One hundred fifty-one subjects, who required single-tooth rehabilitation in the area from position 15 to 25 and from 35 to 45, were enrolled in eight private clinics in Italy. A randomization protocol was applied to allocate the implants in three treatment groups: one control group and two test groups. In the control group, implant placement was performed according to a conventional drilling procedure, and the implants were submerged for 3 months before abutment connection and loading. Implants allocated in the test group 1 and 2 followed an immediate functional loading protocol. While in test group 1, implant placement was performed according to conventional drilling procedure, in test group 2, a modified implant installation procedure (osteotome technique) was applied. Clinical and radiographic examinations were performed during the 5-year follow-up, and technical and biological complications were registered. Although four implants (three in the test group 2 and one in the test group 1) were lost in the immediate functional loading groups in the first year of follow-up, no further implant loss occurred in any of the treatment groups in the following monitoring period up to 5 years. No significant differences on marginal bone level changes were observed between the treatment groups. About 52% of all implants showed bone gain in the period from 1-year to 5-year follow-up. The percentage of all implants that in the same interval of time showed bone loss was about 28%. Although few technical complications were recorded in the period of time up to 5 years, implants showing biological complication were 5.7%. It is suggested that implants installed with a conventional installation technique together with an immediate functional loading protocol may be considered as a valid treatment alternative in a long-term perspective when used in a single-tooth replacement in an esthetic area.


Structure and properties of Gd3Ge4: the orthorhombic RE3Ge4 structures revisited (RE = Y, Tb-Tm).
The new binary compound Gd(3)Ge(4) has been synthesized and its structure has been determined from single-crystal X-ray diffraction. Gd(3)Ge(4) crystallizes in the orthorhombic space group Cmcm (No. 63) with unit cell parameters a = 4.0953(11) A, b = 10.735(3) A, c = 14.335(4) A, and Z = 4. Its structure can be described as corrugated layers of germanium atoms with gadolinium atoms enclosed between them. The bonding arrangement in Gd(3)Ge(4) can also be derived from that of the known compound GdGe (CrB type) through cleavage of the (infinity)(1)[Ge(2)] zigzag chains in GdGe and a subsequent insertion of an extra germanium atom between the resulting triangular fragments. Formally, these characteristics represent isotypism with the Er(3)Ge(4) type (Pearson's oC28). However, re-examination of the crystallography in the whole RE(3)Ge(4) series (RE = Y, Tb-Tm) revealed discrepancies and called into question the accuracy of the originally determined structures. This necessitated a new rationalization of the bonding, which is provided in the context of a comparative discussion concerning both the original and revised structure models, along with an analysis of the trends across the series. The temperature dependence of the magnetic susceptibility of Gd(3)Ge(4) shows that it is paramagnetic at room temperature and undergoes antiferromagnetic ordering below 29 K. Magnetization, resistivity, and calorimetry data for several other members of the RE(3)Ge(4) family are presented as well.


Information loss in limb-lead electrocardiograms compared with twelve-lead tracings in a population survey among the elderly.
A total of 235 telve-lead electrocardiogram tracings representing all those traces with positive Minnesota codings from a population sample of persons aged 65 and over were re-coded on the basis of the six limb-leads alone. The over-all loss of information amounted to about 22.3 per cent of major abnormalities, as defined, but was higher than 50 per cent for some individual abnormalities such as abnormal Q and QS waves. Possible implications of these findings are discussed.


Non-Sciuromorph rodent karyotypes in evolution.
Rodents are, taxonomically, the most species-rich mammalian order. They display a series of special genomic features including the highest karyotypic diversity, frequent occurrence of complex intraspecies chromosome variability, and a variety of unusual chromosomal sex determination mechanisms not encountered in other mammalian taxa. Rodents also have an abundance of cytochemically heterogeneous heterochromatin. There are also instances of extremely rapid karyotype reorganization and speciation not accompanied by significant genetic differentiation. All these peculiarities make it clear that a detailed study of rodent genomic evolution is indispensable to understand the mode and tempo of mammalian evolution. The aim of this review is to update the data obtained by classical and molecular cytogenetics as well as comparative genomics in order to outline the range of old and emerging problems that remain to be resolved.


Emerging Gram-negative bacteria: pathogenic or innocent bystanders.
The current review examines the current literature around 'emerging' Gram-negative bacteria other than Pseudomonas aeruginosa in cystic fibrosis (CF), paying particular focus on the recent literature for those that are more frequently encountered: Pandoraea, Achromobacter, Ralstonia and Stenotrophomonas species. The recent literature is evolving our understanding of the clinical consequences of infection with an 'emerging' Gram-negative bacteria in CF. There is an increase in reported prevalence for many species. They are commonly isolated from patients who already have low baseline lung function. Initial infection can lead to chronic carriage, often with evidence of an associated host immune response and subsequent clinical deterioration. For some species occasional cases of bacteraemia have been reported. There are a number of Gram-negative organisms, other than P. aeruginosa, that can cause chronic infection in patients with CF. There is data to suggest that some of these so-called emerging Gram-negative bacteria are increasing in prevalence and can be pathogenic in patients with CF. The prevalence and clinical consequences however differ from species to species. There is a pressing need to agree a definition of chronic infection for these organisms to compare data between studies.


Electronic nature of the transition state for nucleoside hydrolase. A blueprint for inhibitor design.
A new approach to understanding transition-state structure is presented which involves the sequential application of experimental and computational methods. A family of experimentally determined kinetic isotope effects is fit simultaneously in a vibrational analysis to provide a geometric model of the transition state. The electrostatic potential surface of the geometric model is defined by molecular orbital calculations to detail the electronic nature of the transition state. The method provides both geometric and charge information for the enzyme-stabilized transition state. Electrostatic potential surface calculations were applied to the N-glycohydrolase reaction catalyzed by nucleoside hydrolase from the trypanosome Crithidia fasciculata. A geometric model of the transition-state structure for the enzymatic hydrolysis of inosine by nucleoside hydrolase has been established by the analysis of a family of kinetic isotope effects [Horenstein, B.A., Parkin, D.W., Estupinan, B., & Schramm, V.L. (1991) Biochemistry 30, 10788]. The transition state has substantial oxycarbonium ion character, but the results of electrostatic potential calculations indicate that the transition-state charge is distributed over the ribosyl ring rather than existing as a localized C+-O<==>C = O+ resonance pair. The electrostatic potential surfaces of the substrate and enzyme-bound products differ considerably from that of the transition state. At the transition state both hypoxanthine and ribose demonstrate regions of positive charge. The positive charge on the ribosyl oxycarbonium ion is moderated by association with an enzyme-directed water nucleophile. The enzyme-bound products contain adjacent areas of negative charge. The electrostatic potential surfaces provide novel insights into transition-state structure and the forces causing release of products.(ABSTRACT TRUNCATED AT 250 WORDS)


Visibility graph analysis for brain: scoping review.
In the past two decades, network-based analysis has garnered considerable attention for analyzing time series data across various fields. Time series data can be transformed into graphs or networks using different methods, with the visibility graph (VG) being a widely utilized approach. The VG holds extensive applications in comprehending, identifying, and predicting specific characteristics of time series data. Its practicality extends to domains such as medicine, economics, meteorology, tourism, and others. This research presents a scoping review of scholarly articles published in reputable English-language journals and conferences, focusing on VG-based analysis methods related to brain disorders. The aim is to provide a foundation for further and future research endeavors, beginning with an introduction to the VG and its various types. To achieve this, a systematic search and refinement of relevant articles were conducted in two prominent scientific databases: Google Scholar and Scopus. A total of 51 eligible articles were selected for a comprehensive analysis of the topic. These articles categorized based on publication year, type of VG used, rationale for utilization, machine learning algorithms employed, frequently occurring keywords, top authors and universities, evaluation metrics, applied network properties, and brain disorders examined, such as Epilepsy, Alzheimer's disease, Autism, Alcoholism, Sleep disorders, Fatigue, Depression, and other related conditions. Moreover, there are recommendations for future advancements in research, which involve utilizing cutting-edge techniques like graph machine learning and deep learning. Additionally, the exploration of understudied medical conditions such as attention deficit hyperactivity disorder and Parkinson's disease is also suggested.


[Amylase in serum, amylase excretion and the amylase-creatinine-ratio. Individual variation and diagnostic specifity (author's transl)].
The amylase activity in serum, the amylase excretion and the amylase-creatinine-ratio was investigated in 25 volunteers monthly for one year and daily for two weeks. The intraindividual variation of the amylase-activity in serum showed only small oscillations. The large refernce value of the group and the need to use individual reference values prefer the 24 hour amylase excretion as a diagnostic tool. The amylase-creatinine-ratio showed individual and seasonal large variations. Therefore the ratio is not suitable for diagnostic questions.


Preparation of hierarchical architectures of silica particles with hollow structure and nanoparticle shells: a material for the high reflectivity of UV and visible light.
Silica microcapsules (silica hollow particles) are readily prepared by a single step of the interfacial reaction method, where a W/O/W emulsion is employed effectively. This is a simple (one-step process), inexpensive approach (silica source is sodium silicate) to producing hollow silicas. The addition of NaCl to the sodium silicate solution as the inner water phase of the W/O/W emulsion plainly influenced the shell structure of the silica hollow particles. The increase of the addition of NaCl expanded the size of the mesopores in their silica shell, which reached to macropores (>50 nm). The nanoparticles in the shells of some silica hollow particles attained approximately 200-400 nm in size, which is comparable to the wavelengths of UV and visible light. According to the diffuse reflection spectra of the silica hollow particles in powder form, these particles showed the high reflection of UV and visible light, which increased with added NaCl in the preparation process of the interfacial reaction method. The reflectance of a silica hollow particle from 300 to 800 nm in wavelength was over 90%, which was significantly higher than a common solid (not hollow) silica gel. In addition, even the reflectance of UV light shorter than 300 nm in wavelength was greater than 60%. These characteristic reflections in a wide range of wavelengths were caused by both nanoparticle shells whose sizes are comparable with the wavelength of light and the hollow structures of the main micrometer-sized particles.


[Does Raynaud's disease really exist? (author's transl)].
In a follow-up study of 35 patients with Raynaud's disease attacks of multilocalized vascular disorders were detected in every case, which made the different etiologic definitions of this disease doubtful. We beleive, that a further improvement of our diagnostic facilities, such as pharmacoangiography, will contribute to finding-morphologic disorders in every case of Raynaud's attacks.


Use of expanded deltopectoral skin flaps for facial reconstruction after sizeable benign tumor resections.
The overall unsightliness of expansive benign facial tumors imposes both physical and mental suffering. Although excision is generally the optimal recourse in such instances, reconstructing the subsequent surgical defects is always a critical issue. Herein, we have described our experiences using expanded deltopectoral skin flaps to manage large facial wounds after excising benign tumors. Our endeavor called for retrospective review of 22 patients presenting between July 2007 and March 2017 with various facial growths, including hemangiomas, nevi, and neurofibromas. Depending upon areas of facial involvement, unilateral or bilateral deltopectoral skin flaps were expanded. The stepwise process was as follows: expander implantation, flap transfer, pedicle delay, and eventual separation. Ultimately, all 22 patients undergoing this procedure expressed satisfaction with the results in terms of skin texture, color, and flexibility. This particular method may thus be a reasonable choice for repairing sizeable defects in the wake of benign facial tumor excisions.


An acoustic based, laser induced breakdown method for determining the sizes and concentrations of nanoparticles.
An acoustic, laser induced breakdown (LIBD) method has been developed for determining the sizes and concentrations of nano-sized colloids. The size distributions from a mixture of aquatic nanoparticles are determined by measuring amplitudes of plasma shockwave that are fitted to multi-curve Gaussian distributions displayed in separate peaks with positions corresponding to particle sizes and areas being proportional to concentrations.


Influence of Visual Stimulation-Induced Passive Reproduction of Motor Images in the Brain on Motor Paralysis After Stroke.
Finger flexor spasticity, which is commonly observed among patients with stroke, disrupts finger extension movement, consequently influencing not only upper limb function in daily life but also the outcomes of upper limb therapeutic exercise. Kinesthetic illusion induced by visual stimulation (KINVIS) has been proposed as a potential treatment for spasticity in patients with stroke. However, it remains unclear whether KINVIS intervention alone could improve finger flexor spasticity and finger extension movements without other intervention modalities. Therefore, the current study investigated the effects of a single KINVIS session on finger flexor spasticity, including its underlying neurophysiological mechanisms, and finger extension movements. To this end, 14 patients who experienced their first episode of stroke participated in this study. A computer screen placed over the patient's forearm displayed a pre-recorded mirror image video of the patient's non-paretic hand performing flexion-extension movements during KINVIS. The position and size of the artificial hand were adjusted appropriately to create a perception that the artificial hand was the patient's own. Before and after the 20-min intervention, Modified Ashworth Scale (MAS) scores and active range of finger extension movements of the paretic hand were determined. Accordingly, MAS scores and active metacarpophalangeal joint extension range of motion improved significantly after the intervention. Moreover, additional experimentation was performed using F-waves on eight patients whose spasticity was reduced by KINVIS to determine whether the same intervention also decreased spinal excitability. Our results showed no change in F-wave amplitude and persistence after the intervention. These results demonstrate the potential clinical significance of KINVIS as a novel intervention for improving finger flexor spasticity and extension movements, one of the most significant impairments among patients with stroke. The decrease in finger flexor spasticity following KINVIS may be attributed to neurophysiological changes not detectable by the F-wave, such as changes in presynaptic inhibition of Ia afferents. Further studies are certainly needed to determine the long-term effects of KINVIS on finger spasticity, as well as the neurophysiological mechanisms explaining the reduction in spasticity.


A Comparison of Antimicrobial Efficacy of Silver-based Preventive Restorations (Silver Nitrate, Silver Diamine Fluoride, and Silver Nanoparticles) against Streptococcus mutans Monospecies Biofilm Model.
The ability of the Streptococcus mutans (S. mutans) to form biofilms is not only crucial in the initiation of early childhood caries (ECC) but is also a challenge to its treatment. The current management protocols focus on remineralization and use of antimicrobial formulations which penetrate biofilms, control their formation, and decrease the incidence of caries in children. The paradigm shift toward preventive protocols and increasing antibiotic resistance rekindled the use of silver as a promising antibacterial agent. To gain further insight into the therapeutic potential, aim of the present study was to compare the antibacterial efficacy of silver-based preventive restorations [silver nitrate (AgNO3), silver diamine fluoride (SDF), and silver nanoparticles (AgNPs)] against S. mutans species. Using an ex vivo monospecies biofilm model of S. mutans; the antimicrobial efficacy of three treatment groups (SDF, AgNO3, and AgNPs) was evaluated. There was a significant difference between the negative control and three treatment groups (SDF, AgNO3, and AgNPs). The results showed that the mean diameter of inhibition zones obtained in biofilms treated with AgNPs was 40.3 ± 0.25 mm which was greater than both SDF (37.7 ± 0.18 mm) and AgNO3 (36.26 ± 0.18 mm). The study concluded that the number of viable bacteria was significantly reduced by all three medicaments (p < 0.05). However, AgNPs showed the highest antimicrobial activity in comparison to SDF and AgNO3 against S. mutans biofilm. The present study thus supports that AgNPs are a promising preventive anticaries agent due to their better antibacterial activity in comparison to other silver-based preventive restorations and can be effectively used as an alternative to SDF or AgNO3 for the noninvasive treatment of ECC in the young. Sharma P, Dhawan P, Rajpal SK, et al. A Comparison of Antimicrobial Efficacy of Silver-based Preventive Restorations (Silver Nitrate, Silver Diamine Fluoride, and Silver Nanoparticles) against Streptococcus mutans Monospecies Biofilm Model. Int J Clin Pediatr Dent 2023;16(S-1):S13-S19.


Digital panoramic radiography and cone-beam CT as ancillary tools to detect low bone mineral density in post-menopausal women.
To evaluate the usefulness of the mandibular cortical index (MCI) obtained by digital panoramic radiography (DPR) and by panoramic reconstruction (PR) of cone-beam CT (CBCT) with three different slice thicknesses for the screening of low bone mineral density (BMD) in post-menopausal women. Two trained oral and maxillofacial radiologists assessed the MCI based on the morphology of the mandibular bone cortex (classified as C1, C2 or C3). The DPR and PR of CBCT with slice thicknesses of 5, 15 or 25 mm were compared to the BMD obtained by dual-energy X-ray absorptiometry (DXA) in post-menopausal women. Measures related to accuracy were calculated with MedCalc software. The confidence interval was set at 95%. 54 women (mean age 58.70 ± 7.35 years) participated in the study. The sensitivity and specificity values obtained for DPR were 52.6% and 56.2%, respectively, and values for PR of CBCT with 5, 15, and 25 mm slice thicknesses were 63.1% and 43.7%, 50.0% and 50.0%, and 52.6% and 62.5%, respectively. For the tools evaluated, the positive likelihood ratio ranged from 1.00 to 1.40 and negative likelihood ratio from 0.76 to 1.00. The positive predictive value (PPV) ranged from 70.4 to 76.9% and the negative predictive value (NPV) from 29.6 to 35.7%. Among the examinations, the highest value for area under the curve (AUC) was obtained for CBCT with 25 mm slice thickness (57.6%). The MCI calculated by DPR and CBCT differed with regard to accuracy. Within the limitations of this study, the PR of CBCT with 25 mm slice thicknesses seems to be the most accurate among the examinations evaluated. Should the dentist be attentive, DPR and CBCT may be useful tools for the screening of low BMD in post-menopausal women, facilitating their timely referral for further assessment.


Comparison of the structures of various eukaryotic ferricytochromes c and ferrocytochromes and their antigenic differences.
The nuclear magnetic resonance spectra of various eukaryotic ferricytochromes c and ferrocytochromes c are described. The proteins from the species donkey, cow, dog, rabbit, chicken and pigeon were investigated. The conformations of these proteins detected by NMR were compared to those of horse and tuna cytochromes c and in some cases small differences were found. These differences in structure were shown to correlate with antigenic differences between the various proteins.


Chemical defense in the red seaweed Plocamium brasiliense: spatial variability and differential action on herbivores.
Species of Plocamium are known as prolific sources of halogenated secondary metabolites exhibiting few explored ecological roles. In this study the crude extracts from specimens of P. brasiliense collected in two distinct places, Enseada do Forno and Praia Rasa, Búzios, Estado do Rio de Janeiro, were evaluated as defense against the sea urchin Lytechinus variegatus and the crab Acanthonyx scutiformis. These specimens produce a similar amount of crude extract and also halogenated monoterpene compound-types, but individuals of P. brasiliense from Praia Rasa exhibit a major compound representing about 59% of the total chemicals. Natural concentrations of the crude extracts obtained from both specimens of P. brasiliense significantly inhibited the herbivory by the sea urchin L. variegatus, but had no significant effect on the feeding by A. scutiformis, a crab commonly associated to chemically defended host. Crude extract from P. brasiliense collected at Praia Rasa was more efficient as defense against L. variegatus than that crude extract from populations of this alga from Enseada do Forno, probably due to presence of a major secondary metabolite. These two studied population live under different environmental conditions, but they are only about 30 Km apart. However, it is impossible to affirm that environmental characteristics (abiotic or biotic) would be responsible for the difference of defensive potential found in the two populations of P. brasiliense studied here. Further genetic studies will be necessary to clarify this question and to explain why populations of a single species living in different but close locations can exhibit distinct chemicals.


Inverse design of equilibrium cluster fluids applied to a physically informed model.
Inverse design strategies have proven highly useful for the discovery of interaction potentials that prompt self-assembly of a variety of interesting structures. However, often the optimized particle interactions do not have a direct relationship to experimental systems. In this work, we show that Relative Entropy minimization is able to discover physically meaningful parameter sets for a model interaction built from depletion attraction and electrostatic repulsion that yield self-assembly of size-specific clusters. We then explore the sensitivity of the optimized interaction potentials with respect to deviations in the underlying physical quantities, showing that clustering behavior is largely preserved even as the optimized parameters are perturbed.


Protein kinase C signalling in leukemia.
The protein kinase C (PKC) family of proteins includes several kinases that share structural homology, but at the same time exhibit substantial functional diversity. There is a significant amount of evidence establishing distinct patterns of expression and function for different PKC isoforms and groups in different leukemias. Although most members of this family promote leukemic cell survival and growth, others exhibit opposing effects and participate in the generation of antileukemic responses. This review summarizes work in this field on the relevance of distinct members of the PKC family in the pathophysiology of myeloid and lymphoid leukemias. The clinical-therapeutic potential of such ongoing work for the treatment of future development of novel approaches for the treatment of different types of leukemias is discussed.


Dr Monk's medical digest.
The Liber passionalis is an early and hitherto mostly unexplored example of a composite medical work on diagnosis and therapy, similar to the better-known compilations circulating under the titles Petroncellus and Gariopontus (Passionarius Galieni). It shows the efforts made to provide comprehensive coverage of morbid conditions drawn from a choice of the best sources available to the compiler, sources which in some instances complement or enhance our knowledge of ancient medicine in a way overlooked by specialists in the field for a long time and which provide the best clue when trying to assess medical expertise at the turn of the first millennium. The paper explores the transmission, structure and sources of the Liber passionalis, touching on the body of medical literature available in the early Middle Ages.


Roche RIA and Abbott EIA carcinoembryonic antigen assays compared.
We have evaluated Roche Diagnostics' RIA-CEA and Abbott Diagnostics' EIA-CEA methods for precision, normal reference interval, concordance, and correlation of malignant disease with increase in carcinoembryonic antigen (CEA) in plasma. In examining concordance, we used data on 138 patients with primary carcinomas of the breast, colon, lung, or pancreas, each further classified by extent of dissemination. We find the two methods to be comparably precise. The respective upper reference limits of normal for the Roche and Abbott methods were determined to be 5.0 micrograms/L and 4.6 micrograms/L. The regression equation for a log transformation of the 177 data points is y = 0.966x + 0.03, where x = Roche and y = Abbott, with a correlation coefficient of 0.948. According to the criteria we used, the concordance was 78.7%. The largest discordance was observed in widely disseminated disease states and in cancers of the colon and pancreas. Paired data analysis of discordance indicated greater increases in apparent CEA by the Abbott method in most colon cancers with liver involvement; six of the eight discordant pancreatic cancers had higher Roche-CEA values. CEA heterogeneity and the role of the liver in CEA metabolism appear to contribute to the observed differences. We show why the two methods should not be used interchangeably, and that baseline values for CEA must be established for each method.